Allure Cosmeceuticals




Rapid enumeration of physiologically active bacteria in purified water used in the pharmaceutical manufacturing process

Physiologically active bacteria in purified water used in the manufacturing process of pharmaceutical products were enumerated in situ. Bacteria with growth potential were enumerated using the micro-colony technique and direct viable counting (DVC), followed by 24 h of incubation in 100-fold diluted SCDB (Soybean Casein Digest Broth) at 30 °C. Respiring and esterase-active bacteria were detected by fluorescent staining with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and 6-carboxyfluorescein diacetate (6CFDA), respectively. A large number of bacteria in purified water retained physiological activity, while most could not form colonies on conventional media. The techniques applied in this study enabled bacteria to be counted within 24 h so results could be available within one working day. These rapid and convenient techniques should be useful for the systematic monitoring of bacteria in water used for pharmaceutical manufacturing.

  1. Kawai,N. Yamaguchi andM. Nasu.Journal of Applied Microbiology. Volume 86, Issue 3, pages 496–504, March 1999. DOI: 10.1046/j.1365-2672.1999.00689.x

Free radical scavenging activity of a novel antioxidative peptide purified from hydrolysate of bullfrog skin, Rana catesbeiana Shaw


In the present study, a peptide having antioxidant properties was isolated from bullfrog skin protein, Rana catesbeiana Shaw. Bullfrog skin protein was hydrolyzed using alcalase, neutrase, pepsin, papain, α-chymotrypsin and trypsin. Antioxidant activities of respective hydrolysates were evaluated using lipid peroxidation inhibition assay and direct free radical scavenging activity by using electron spin resonance (ESR) spectrometer. Among hydrolysates, alcalase derived hydrolysate exhibited the highest antioxidant activities than those of other enzyme hydrolysates. In order to purity a peptide having potent antioxidant properties, alcalase hydrolysate was separated using consecutive chromatographic methods on a Hiprep 16/10 DEAE FF anion exchange column, Superdex Peptide 10/300 GL gel filtration column and highan octadecylsilane (ODS) C18 reversed phase column. Finally, a potent antioxidative peptide was isolated and its sequence was identified to be LEELEEELEGCE (1487 Da) by Q-TOF ESI mass spectroscopy. This antioxidant peptide from bullfrog skin protein (APBSP) inhibited lipid peroxidation higher than that of α-tocopherol as positive control and efficiently quenched different sources of free radicals: DPPH radical (IC50 = 16.1 μM), hydroxyl radical (IC50 = 12.8 μM), superoxide radical (IC50 = 34.0 μM) and peroxyl radical (IC50 = 32.6 μM). Moreover, MTT assay showed that this peptide does not exert any cytotoxicity on human embryonic lung fibroblasts cell line (MRC-5).

Zhong-Ji Qian,Won-Kyo Jung,Se-Kwon Kim.Bioresource Technology. Volume 99, Issue 6, April 2008, Pages 1690–1698.doi:10.1016/j.biortech.2007.04.005


Safflower Oil

Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of antiinflammatory and antiproliferative metabolites


In the skin epidermis, the metabolism of polyunsaturated fatty acids (PUFAs) is highly active. Dietary deficiency of linoleic acid (LA), the major 18-carbon n−6 PUFA in normal epidermis, results in a characteristic scaly skin disorder and excessive epidermal water loss. Because of the inability of normal skin epidermis to desaturate LA to γ-linolenic acid, it is transformed by epidermal 15-lipoxygenase to mainly 13-hydroxyoctadecadienoic acid, which functionally exerts antiproliferative properties in the tissue. In contrast, compared with LA, arachidonic acid (AA) is a relatively minor 20-carbon n−6 PUFA in the skin and is metabolized via the cyclooxygenase pathway, predominantly to the prostaglandins E2, F2α, and D2. AA is also metabolized via the 15-lipoxygenase pathway, predominantly to 15-hydroxyeicosatetraenoic acid. At low concentrations, the prostaglandins function to modulate normal skin physiologic processes, whereas at high concentrations they induce inflammatory processes. PUFAs derived from other dietary oils are also transformed mainly into monohydroxy fatty acids. For instance, epidermal 15-lipoxygenase transforms dihomo-γ-linolenic acid (20:3n−6) to 15-hydroxyeicosatrienoic acid, eicosapentaenoic acid (20:5n−3) to 15-hydroxyeicosapentaenoic acid, and docosahexaenoic acid (22:6n−3) to 17-hydroxydocosahexaenoic acid, respectively. These monohydroxy acids exhibit antiinflammatory properties in vitro. Thus, supplementation of diets with appropriate purified vegetable oils, fish oil, or both may generate local cutaneous antiinflammatory and antiproliferative metabolites which could serve as less toxic in vivo monotherapies or as adjuncts to standard therapeutic regimens for the management of inflammatory skin disorders.

Ziboh, Vincent A., Craig C. Miller, and Yunhi Cho. “Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of antiinflammatory and antiproliferative metabolites.” The American journal of clinical nutrition 71.1 (2000): 361s-366s.

Effects of dietary safflower oil or hydrogenated coconut oil on growth rate and on some blood and tissue components of pigs fed a fat-free diet.


The effects of diets containing no fat, 3% hydrogenated coconut oil (HCO) or graded levels, 0.1, 0.5, 1.0 or 3%, of safflower oil (SO) on serum cholesterol, lipids and protein level, on total heart and liver cholesterol and lipid and on growth rate and skin condition were studied in weanling Yorkshire and Yorkshire x Hampshire pigs. Pigs fed on the fat-free diet for 21 weeks developed severe skin lesions not observed in pigs given HCO diets. Highly significant elevation of serum, liver and heart lipid and liver cholesterol, and a highly significant depression of total serum protein were observed with HCO or fatfree diets. Serum cholesterol was significantly higher with HCO than with fat-free diet or diets containing SO during the repletion period. Total heart cholesterol, growth rate and erythrocyte fragility were unaffected by diets. It is concluded that growth rate is not adversely affected in the pig by fat-free diets and that HCO does not produce skin lesions in the pig characteristic of fatty acid deficiency. Of all the correlation coefficients analysed, only the serum cholesterol and total lipids were consistently highly significantly correlated, while serum protein was inversely related to total liver lipid.

Babatunde, G. M., et al. “Effects of dietary safflower oil or hydrogenated coconut oil on growth rate and on some blood and tissue components of pigs fed a fat-free diet.” Journal of Nutrition 92 (1967): 293-302.;jsessionid=339AEF6BEB91C2EA91293F4EDA00AC2E

Nutritional studies with the guinea pig. 10. Determination of the linoleic acid requirement.


For parts 8 and 9 see Abst. 672, Vol. 34.

  1. Guineapigs were given at 2 to 5 days of age a diet in which the fat was maize oil, trilaurin, safflower oil, or starch lipid (Mazola maize oil). After different periods on the diets the guineapigs were starved overnight before being killed; red cell lipids were extracted with ethanol and ether and the fatty acids were estimated by gas chromatography. During 6 weeks addition of 1 to 15% maize or safflower oil to the diet gave good weight gain. With 0.17% linoleic acid as the only source of fat the animals survived but most had dermatitis; only with 1.31% linoleic acid was dermatitis completely absent. Guineapigs on diets containing 1.31% linoleic acid or 7.3% maize oil for 8 months showed no clinical sign of essential fatty acid deficiency. On such diets the ratio of 5, 8, 11-eicosatrienoic to arachidonic acid was 0.17 and of oleic to linoleic 1.4. The former ratio has been used as a test for essential fatty acid sufficiency but reasons are given for preferring the latter. Homogenates of liver from guineapigs deprived of linoleic acid oxidized citrate rapidly.-D. E. M. Lawson.

Reid, M. E., et al. “Nutritional studies with the guinea pig. 10. Determination of the linoleic acid requirement.” Journal of Nutrition 82 (1964): 401-408.

Skin and hair aerosol foam preparations containing an alkyl polyglycoside and vegetable oil


A water-based composition for the treatment of hair or skin containing an active-substance combination of cosmetic components consisting of

(a) an alkyl polyglycoside corresponding to general formula (I):

RO–(Z)x (I)

in which R is an alkyl radical containing 6 to 22 carbon atoms, Z is a mono- or oligosaccharide and x is a number of 1.1 to 5, or adducts thereof with 1 to 10 moles of ethylene oxide or propylene oxide,

(b) a polymer, and

(c) a vegetable oil selected from kukui nut oil, almond oil, walnut oil, peach kernel oil, avocado oil, tea tree oil, soya oil, sesame oil, sunflower seed oil, tsubaki oil, evening primrose oil, rice bran oil, palm kernel oil, mango kernel oil, meadow foam oil, thistle oil, macadamia nut oil, grape seed oil, apricot kernel oil, babassu oil, olive oil, wheat germ oil, pumpkin seed oil, mallow oil, hazel nut oil, safflower oil, jojoba oil, canola oil, sasanqua oil and shea butter.

Mueller, Reinhard, et al. “Skin and hair aerosol foam preparations containing an alkyl polyglycoside and vegetable oil.” U.S. Patent No. 6,045,779. 4 Apr. 2000.

Reversal of experimental essential fatty acid deficiency by cutaneous administration of safflower oil.


The intriguing observation that cutaneous application of essential fatty acid (EFA)-rich oil corrects the biochemical abnormalities of EFA deficiency was evaluated in EFA-deficient rats. Approximately 185 mg of safflower oil (140 mg of linoleic acid) were applied daily for 15 days to the kin of EFA-deficient rats. Before and after treatment with the safflower oil, the fatty acid patterns of plasma and erythrocyte phospholipid as well as of plasma triglyceride and cholesterol ester fractions were determined. The linoleic and arachidonic acid content of both plasma and erythrocyte phospholipid increased, while the eicosatrienoic acid content of both fractions decreased. The linoleic acid content of plasma triglyceride increased with safflower oil treatment, but little change occurred in the almost undetectable pretreatment levels of arachidonic and eicosatrienoic acid. In the plasma cholesterol ester fraction, arachidonic acid increased with treatment and eicosatrienoic acid decreased, but the small increase in the linoleic acid content was not statistically significant. Thus, the study confirms the observation that cutaneous application of EFA-rich oils reverses the plasma biochemical manifestation of EFA deficiency. In addition cutaneously applied EFA-rich oils reversed the biochemical manifestations of EFA deficiency in erythrocytes. Whether or not cutaneous application of such oils will prevent EFA deficiency, however, remains to be proven.

Böhles, H., M. A. Bieber, and W. C. Heird. “Reversal of experimental essential fatty acid deficiency by cutaneous administration of safflower oil.” The American journal of clinical nutrition 29.4 (1976): 398-401.

Differential effects of safflower oil versus fish oil feeding on insulin-stimulated glycogen synthesis, glycolysis, and pyruvate dehydrogenase flux in skeletal muscle: a 13C nuclear magnetic resonance study.


To examine the effects of safflower oil versus fish oil feeding on in vivo intramuscular glucose metabolism and relative pyruvate dehydrogenase (PDH) versus tricarboxylic acid (TCA) cycle flux, rats were pair-fed on diets consisting of 1) 59% safflower oil, 2) 59% menhaden fish oil, or 3) 59% carbohydrate (control) in calories. Rates of glycolysis and glycogen synthesis were assessed by monitoring [1-(13)C]glucose label incorporation into [1-(13)C]glycogen, [3-(13)C]lactate, and [3-(13)C]alanine in the hindlimb of awake rats via 13C nuclear magnetic resonance (NMR) spectroscopy during a euglycemic (approximately 6 mmol/l) hyperinsulinemic (approximately 180 microU/ml) clamp. A steady-state isotopic analysis of lactate, alanine, and glutamate was used to determine the relative PDH versus TCA cycle flux present in muscle under these conditions. The safflower oil-fed rats were insulin resistant compared with control and fish oil-fed rats, as reflected by a markedly reduced glucose infusion rate (Ginf) during the clamp (21.4 +/- 2.3 vs. 31.6 +/- 2.8 and 31.7 +/- 1.9 mg x kg(-1) x min(-1) in safflower oil versus control and fish oil groups, respectively, P < 0.006). This decrease in insulin-stimulated glucose disposal in the safflower oil group was associated with a lower rate of glycolysis (21.7 +/- 2.2 nmol x g(-1) x min(-1)) versus control (62.1 +/- 10.3 nmol x g(-1) x min(-1), P < 0.001) and versus fish oil (45.7 +/- 6.7 nmol x g(-1) x min(-1), P < 0.04), as no change in glycogen synthesis (103 +/- 15, 133 +/- 19, and 125 +/- 14 nmol x g(-1) x min(-1) in safflower oil, fish oil, and control, respectively) was detected. The intramuscular triglyceride (TG) content was increased in the safflower oil group (7.3 +/- 0.8 micromol/g) compared with the control group (5.2 +/- 0.8 micromol/g, P < 0.05) and the fish oil group (3.6 +/- 1.1 micromol/g, P < 0.01). Conversely, the percent PDH versus TCA cycle flux was decreased in the safflower oil (43 +/- 8%) versus the control (73 +/- 8%, P < 0.01) and fish oil (64 +/- 6%, P < 0.05) groups. These data suggest that the reduced insulin-stimulated glucose disposal attributed to safflower oil feeding was a consequence of reduced glycolytic flux associated with an increase in relative free fatty acid/ketone oxidation versus TCA cycle flux, whereas fish oil feeding did not alter glucose metabolism and may in part be protective of insulin-stimulated glucose disposal by limiting intramuscular TG deposition.

Jucker, Beat M., et al. “Differential effects of safflower oil versus fish oil feeding on insulin-stimulated glycogen synthesis, glycolysis, and pyruvate dehydrogenase flux in skeletal muscle: a 13C nuclear magnetic resonance study.” Diabetes 48.1 (1999): 134-140. doi: 10.2337/diabetes.48.1.134

Effects of dietary perilla oil, soybean oil and safflower oil on 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH)-induced mammary gland and colon carcinogenesis in female SD rats


The effects of diet supplemented with perilla oil, which contains a large amount of n-3 α-linolenic acid, and n-6 linoleic acid rich soybean and safflower oil supplemented diets on 7,12-dimethylbenz[a]anthracene (DMIBA)- and 1,2- diinethylliydrazine (DMH)-induced mammary gland and colon carcinogenesis were investigated in female SD rats. Groups of 23 or 24,5 week old animals were first given three s.c. injections of 40 mg/kg body wt DM11 followed by a single intragastric administration of 50 mg/kg body wt DMBA within 2 weeks of the commencement. Starting 1 week after the DMBA treatment, they were administered pellet diet containing 10% perilla oil, soybean oil or safflower oil for the succeeding 33 weeks. Histological examination revealed that the resultant numbers of mammary tumors per rat were significantly lower in rats given perilla oil diet (4.4 ± 2.5) than in the soybean oil diet group (6.5 ± 3.9). Furthermore, colon tumor incidence was significantly lower in animals receiving the perilla oil supplement (18.2%) than in those given safflower oil diet (47.4%), and the numbers of colon tumors per rat tended to be lowest in rats administered perilla oil. Also the incidence of nephroblastomas in rats receiving perilla oil diet (0%) was significantly lower than that for the soybean oil diet group (23.8%). The results thus indicate that the α-linolenic acid (n-3)-rich perilla oil diet inhibits development of mammary gland, colon and kidney tumors as compared to linoleic acid (n-6)-rich safflower or soybean oil diet.

Hirose, Massao, et al. “Effects of dietary perilla oil, soybean oil and safflower oil on 7, 12-dimethylbenz [a] anthracene (DMBA) and 1, 2-dimethylhydrazine (DMH)-induced mammary gland and colon carcinogenesis in female SD rats.” Carcinogenesis 11.5 (1990): 731-735. doi: 10.1093/carcin/11.5.731

Dietary supplement for preventing or reducing shedding by animals


A dietary supplement for animals, comprising safflower oil, sunflower oil, olive oil, soya oil, cod liver oil, lecithin, natural flavors, herbs, garlic, and zinc. When fed to a dog or cat daily in a proper dosage, the supplement reduces or eliminates non-seasonal shedding and promotes healthy skin and a glossy, silky coat, without affecting the dog’s or cat’s natural shedding cycle and without causing any harmful effects. The composition also may be administered topically.

Allen, Barbara A. “Supplement containing safflower oil, sunflower oil, olive oil, soya oil, cod liver oil, lecithin, natural flavors, herbs, garlic and zinc.” U.S. Patent No. 5,965,153. 12 Oct. 1999.

On the demonstration of ω-3 essential-fatty-acid deficiency in humans


In the few reported cases of human ω-3 fatty acid deficiency, the clinical conditions described probably resulted from either combined ω-3 and ω-6 fatty acid deficiencies (leading to skin lesions) or from complications arising from special medical situations, such as long-term total parental nutrition with an ω-3-deficient fat preparation, such as safflower oil. These reports plus the experimental animal studies do call attention to the fact that those who devise enteral formula diets or parenteral fluids should always consider that both series of fatty acids (ω-6 and ω-3) must be included in the total diet as essential nutrients. This consideration is especially important if the feeding period is months or even years or if in the short-term continuous glucose infusion blocks the release of these essential fatty acids from adipose tissue stores. The deficient state, biochemically identifiable, can arise in a few days under the latter circumstance.

Anderson, Gregory, and William E. Connor. “On the demonstration of ω-3 essential-fatty-acid deficiency in humans.” American Journal of Clinical Nutrition 49.4 (1989): 585-587.


Hydrolyzed Collagen
Hyrdrolyzed Collagen is a processed form of Collagen that is obtained by breaking down Collagen fibers utilizing heat or caustic solutions. It contains 20 different amino acids, including 8 of the 9 essential amino acids. Essential amino acids cannot be created the human body, which means that the only way our bodies can acquire them is through ingestion.(

Effects of a hydrolyzed collagen dressing on the healing of open wounds in dogs

Steven F. Swaim, DVM, MS Robert L. Gillette, DVM, MSE Eva A. Sartin, DVM, PhD Sherri H. Hinkle, BS Shindok L. Coolman, MS. American Journal of Veterinary Research. December 2000, Vol. 61, No. 12, Pages 1574-1578. doi: 10.2460/ajvr.2000.61.1574

Hydrolyzed collagen-based hydrogel with salt and pH-responsiveness properties

  1. Pourjavadi, H. Salimi and M. Kurdtabar. Journal of Applied Polymer Science.Volume 106, Issue 4, pages 2371–2379, 15 November 2007. DOI: 10.1002/app.26682

The Effects of Acetic Acid on Collagen Cross-Links

Peter F. Davison, Donald J. Cannon, Lorna P. Andersson. Connective Tissue Research, 1972, Vol. 1, No. 3 : Pages 205-216. (doi: 10.3109/03008207209152076)

Optimization of antioxidant activity by response surface methodology in hydrolysates of jellyfish (Rhopilema esculentum ) umbrella collagen

Yong-liang Zhuang, Xue Zhao, Ba-fang Li. Journal of Zhejiang University SCIENCE B. August 2009, Volume 10, Issue 8, pp 572-579.



The influence of water, glycerin, paraffin oil and ethanol on skin mechanics.


Moisturizers and emollients do not only smooth the skin but also make it more supple. To clarify this effect, the short-term influence of tap water, paraffin oil, ethanol and glycerin on skin mechanics was studied. These substances are all common ingredients in moisturizers and emollients. Significant changes were seen already after 10 min of application. The distensibility and hysteresis (creep phenomenon) showed the most pronounced changes. Water and paraffin oil application caused significant (p < 0.03) increases after 10 min of application. The changes persisted for at least 10 min following paraffin oil application, while they disappeared sooner following water application. Application of ethanol had a negative effect on distensibility (p < 0.03). Glycerin appears to have a slow onset of action, but with the changes continuing even after application was stopped. The changes induced by glycerin appear to be similar to those induced by water and paraffin oil. The study shows that some of the most common ingredients in moisturizers and emollients are capable of inducing significant changes in the mechanical properties of human skin in vivo even after a 10-min application, suggesting that the outermost layers of the epidermis play an important role in skin mechanics.

Overgaard, Olsen L., and G. B. Jemec. “The influence of water, glycerin, paraffin oil and ethanol on skin mechanics.” Acta dermato-venereologica 73.6 (1993): 404-406.

Gravimetric analysis and differential scanning calorimetric studies on glycerin-induced skin hydration


A thermal gravimetric analysis (TGA) and a differential scanning calorimetry (DSC) were carried out to characterize the water property and an alteration of lipid phase transition of stratum corneum (SC) by glycerin. In addition, the relationship between steady state skin permeation rate and skin hydration in various concentrations of glycerin was investigated. Water vapor absorption-desorption was studied in the hairless mouse stratum corneum. Dry SC samples were exposed to different conc. of glycerin (0–50%) followed by exposure to dry air and the change in weight property was monitored over time by use of TGA. In DSC study, significant decrease in AH of the lipid transition in 10% glycerin and water treated sample: the heat of lipid transition of normal, water, 10% glycerin treated SC were 6.058, 4.412 and 4.316 mJ/mg, respectively. In 10% glycerin treated SCs, the Tc of water shifts around 129°C, corresponding to the weakly bound secondary water. In 40% glycerin treated SC, the Tc of water shifts to 144°C corresponding to strongly bound primary water. There was a good correlation between the hydration property of the skin and the steady state skin flux with the correlation coefficient (r2=0.94). As the hydration increased, the steady state flux increased. As glycerin concentration increased, hydration property decreased. High diffusivity induced by the hydration effect of glycerin and water could be the major contributing factor for the enhanced skin permeation of nicotinic acid (NA).

Lee, Ae-Ri Cho, and Hee Kyung Moon. “Gravimetric analysis and differential scanning calorimetric studies on glycerin-induced skin hydration.” Archives of pharmacal research 30.11 (2007): 1489-1495. DOI 10.1007/BF02977376

Nonlathering cleansing mousse with skin conditioning benefits


A mild skin-cleansing, nonlathering mousse-forming emulsion which leaves the skin, after washing, feeling moisturized, soft and smooth, and which does not require rinsing. The emulsion comprises:

  1. from about 95% to about 99.5% of a concentrate containing by weight of the concentrate:
  2. from 1.5% to 15% nonionic surfactant;
  3. from about 0.2% to about 5% of a C12 -C22 saturated, straight chain fatty alcohol;
  4. from about 5% to about 35% of an emollient other than a C12 -C22 fatty alcohol;
  5. from about 5% to about 20% of a skin moisturizer;
  6. the balance water; the weight ratio of surfactant:emollient plus fatty alcohol being from about 0.1:1 to about 0.5:1; and
  7. from 0.5% to 5% of a moderately water-soluble propellant (e.g., nitrous oxide).

The mousse emulsion is packaged in a pressurized aerosol container.

Snyder, William E. “Nonlathering cleansing mousse with skin conditioning benefits.” U.S. Patent No. 4,806,262. 21 Feb. 1989.

Plasticising effect of water and glycerin on human skin in vivo


Application of water and glycerin is known to influence skin mechanics. The kinetics of these processes are of great interest. A study was performed to show the immediate changes in skin-mechanics. A Dermaflex machine (R) was used to study 23 healthy volunteers. Water or glycerin was applied to the flexorside of the forearm, and readings were made after 3, 6, 9, 12 and 15 min. Regional untreated skin served as baseline. In agreement with earlier studies both substances influenced hysteresis. Water caused a significant increase in hysteresis after 12 and 15 min of hydration (P<0.01). Glycerin caused significantly increased hysteresis after 3 min (P<0.05) and the effect continued to the end of the observation period. No significant differences were seen in the distensibility. The onset of action is rapid for both substances, and the effects are therefore supposed to take place in the outermost layers of epidermis. The effect of glycerin on the hysteresis is more rapid in onset than that of water. Comparing the permeability coefficients, the effect on the mechanical properties of the skin does not appear to be determined by the permeability coefficients as water has a higher permeability coefficient but induces smaller changes than glycerin. Water alone does not appear to be the optimal plasticiser of human skin and other substances soluble in both water and lipids may have an even greater influence on skin mechanics in vivo.

Pedersen, L. K., and G. B. E. Jemec. “Plasticising effect of water and glycerin on human skin in vivo.” Journal of dermatological science 19.1 (1999): 48-52. DOI:

Mechanism of Enhancement of Percutaneous Absorption of Molsidomine by Oleic Acid


The mechanism of percutaneous absorption of molsidomine, enhanced by a two-component system consisting of oleic acid and propylene glycol, was studied in vitro and in vitro in rats. About 10-20% of the oleic acid was absorbed from the skin independently of the oleic acid-propylene glycol ratio. In contrast, about 95% of molsidomine and propylene glycol were transdermally absorbed from the two-component system containing 10% oleic acid in 6 h. The permeability (percent of dose) of molsidomine through the excised rat skin was comparable to that of propylene glycol (both about 80% in 24h). These results suggest that the molsidomine and propylene glycol permeated simultaneously through rat skin. Our proposed mechanism of percutaneous absorption of molsidomine assumes that oleic acid and propylene glycol penetrate into the stratum corneum and improve the permeability of the skin by dissolving hard lipoidal components, and then molsidomine, dissolved in the propylene glycol, passes through the modified stratum corneum.

YAMADA, MASAYUKI, YOSHIAKI UDA, and Yusuke Tanigawara. “Mechanism of enhancement of percutaneous absorption of molsidomine by oleic acid.” Chemical and pharmaceutical bulletin 35.8 (1987): 3399-3406.

Nonlathering cleansing mousse with skin conditioning benefits


A mild skin-cleansing, nonlathering mousse-forming emulsion which leaves the skin, after washing, feeling moisturized, soft and smooth, and which does not require rinsing. The emulsion comprises:

  1. from about 95% to about 99.5% of a concentrate containing by weight of the concentrate:
  2. from 1.5% to 15% nonionic surfactant;
  3. from about 0.2% to about 5% of a C12 -C22 saturated, straight chain fatty alcohol;
  4. from about 5% to about 35% of an emollient other than a C12 -C22 fatty alcohol;
  5. from about 5% to about 20% of a skin moisturizer;
  6. the balance water; the weight ratio of surfactant:emollient plus fatty alcohol being from about 0.1:1 to about 0.5:1; and
  7. from 0.5% to 5% of a moderately water-soluble propellant (e.g., nitrous oxide).

The mousse emulsion is packaged in a pressurized aerosol container.

Snyder, William E. “Nonlathering cleansing mousse with skin conditioning benefits.” U.S. Patent No. 4,708,813. 24 Nov. 1987.

Mild skin cleansing aerosol mousse with skin feel and moisturization benefits


A mild skin-cleansing aerosol mousse-forming emulsion providing benefits in leaving the skin after washing feeling not taut and dry, but moisturized, soft and smooth. The product also provides abundant rich creamy foam. The cleansing mousse emulsion comprises:

  1. 88% to 97% of a concentrate containing by weight of the concentrate:
  2. from 3% to 20% of a mild nonsoap anionic or amphoteric surfactant;
  3. a polymeric skin feel aid at 0.05% to 5%;
  4. a moisturizer at 10% to 60%, preferably glycerin;
  5. the balance water; and
  6. from 3% to 12% of a propellant by weight of the total emulsion.

Schmidt, Robert R., Raymond H. Fortna, and Harold H. Beyer. “Anionic Or Amphoteric Surfactant, Polymeric Skin Feel Aid, Moisturizer, Water, Propellant.” U.S. Patent No. 5,002,680. 26 Mar. 1991.

Method for reducing skin irritation associated with drug/penetration enhancer compositions


A composition and method for reducing the skin irritation properties of a transdermal drug/enhancer composition which comprises incorporating into said composition, either prior to or at the time of application the skin, an effective amount of glycerin. When incorporated into the drug/enhancer composition prior to application to the skin the glycerin content will be between about 0.1 and 70 wt. %, preferably between about 1.0 and 50 wt. % and most preferably between about 5.0 and 20 wt. % of the composition.

Patel, Dinesh C., and Charles D. Ebert. “Containing glycerin.” U.S. Patent No. 4,855,294. 8 Aug. 1989.

Effects of postmilking teat treatment on the colonization of Staphylococcus aureus on chapped teat skin.


Sixteen Holstein cows were used to test the effect of postmilking teat treatment on colonization and intramammary infection by Staphylococcus aureus on chapped teats. Treatments were (1) chapping the teat and using 1% I2/10% glycerin postdip solution, (2) 1% I2/10% glycerin postdip solution on nonchapped teats, (3) chapping the teat and using 10% glycerin postdip solution, (4) chapping the teat and not using a postdip solution. All mammary glands were free of S aureus teat skin colonization and intramammary infection at the start of the study. Teats selected for chapping were dipped in 1N NaOH prior to 3 applications of S aureus broth culture; cultures were applied at 12-hour intervals on all teats. Treatments were applied after each milking for 30 days and were initiated after the second broth dip. Teat skin swab specimens and milk samples were collected before treatment application. Teat skin condition was scored daily. Nonchapped teats (treatment 2) did not support skin or orifice colonization by S aureus. Treatment-1 teats healed most rapidly and supported less colonization in skin and orifice than did treatment-3 and -4 teats. Teat skin scores and skin colonization were lower for treatment-3 than treatment-4 teats. A correlation between teat skin colonization and teat skin conditions was found. Two intramammary infections were found in treatment-4 quarters and 1 in a treatment-3 quarter.

Fox, L. K., et al. “Effects of postmilking teat treatment on the colonization of Staphylococcus aureus on chapped teat skin.” American journal of veterinary research 52.6 (1991): 799-802.

The Relationship of Nonspecific Airway Responsiveness and Atopy to the Rate of Decline of Lung function: The Normative Aging Study


Nonspecific airway hyperresponsiveness and atopy have been postulated to be risk factors that predispose individuals to the development of chronic obstructive pulmonary disease. The purpose of the present study was to examine the relationship of methacholine airway responsiveness and markers of atopy to rate of decline in lung function among 790 men, age 40 to 79 yr, followed in the Normative Aging Study. Airway responsiveness was assessed at the end of follow-up, which ranged from 14 to 24 yr. Multiple linear regression analysis indicated that greater methacholine airway responsiveness was associated with more rapid annual FEV1 decline. Stratified analysis suggested that this association was stronger among skin test-negative, current smokers. No significant relationship was found between serum IgE level and annual FEV1 decline. A weak but statistically significant correlation between eosinophil count and mean annual FEV1 decline was noted among skin test-negative individuals (r = −0.08; p = 0.03). Results from the present study do not show a clear association between atopy and decline in FEV1. These data, however, do indicate an independent association between heightened methacholine responsiveness on decline in FEV1 in adult males.

Parker, Donna R., et al. “The relationship of nonspecific airway responsiveness and atopy to the rate of decline of lung function.” Am Rev Respir Dis 141 (1990): 589-594. doi: 10.1164/ajrccm/141.3.589

Avocado Oil

Lipid vesicles containing avocado oil unsaponifiables


Disclosed are oil-filled paucilamellar lipid vesicles containing at least one non-phospholipid amphiphile as the primary lipid of the vesicle bilayers and avocado oil unsaponifiables. The vesicles are particularly useful for delivering dermatological, cosmetic and pharmaceutical formulations. A method of manufacture for these vesicles is also disclosed.

Mathur, Rajiv. “Lipid vesicles containing avocado oil unsaponifiables.” U.S. Patent No. 5,643,600. 1 Jul. 1997.

Microencapsulation of avocado oil by spray drying using whey protein and maltodextrin


Cold pressed avocado oil was microencapsulated by spray drying in four different wall systems consisting of whey protein isolate (WPI) alone or in combination with maltodextrin (MD) DE 5 at various ratios (90 : 10, 50 : 50 and 10 : 90). The WPI only or WPI/MD (90 : 10) powders were spherical and smooth, whereas the WPI/MD (50 : 50 and 10 : 90) powders exhibited pronounced surface collapse. Increasing the MD ratio resulted in higher bulk density and wettability, probably due to more compact physical structure and hydrophilic wall matrix. Surface free oil contents and microencapsulation efficiencies of powders were 11–16% and 45–66%, respectively, and no significant differences were observed between the samples. The crude avocado oil used in this study appeared to be stable against oxidation at cold and ambient temperatures, irrespective of microencapsulation. However, at high temperature of 60°C, the oxidative stability decreased significantly in all cases but it was improved to some extent by microencapsulation.

Bae, E. K., and S. J. Lee. “Microencapsulation of avocado oil by spray drying using whey protein and maltodextrin.” Journal of Microencapsulation 25.8 (2008): 549-560. DOI:10.1080/02652040802075682

Vitamin B12 Cream Containing Avocado Oil in the Therapy of Plaque Psoriasis


Background: There are already many effective topical therapies available for use in the treatment of chronic plaque psoriasis. Unfortunately, these treatments are often associated with a rather significant risk of undesirable effects. Objective and Methods: In this randomized, prospective clinical trial, the effects of the vitamin D3 analog calcipotriol were evaluated against those of a recently developed vitamin B12 cream containing avocado oil in an intraindividual right/left-side comparison. The trial population consisted of 13 patients, 10 men and 3 women, with chronic plaque psoriasis. The observation period was 12 weeks; the effects of therapy were assessed on the basis of a PASI score adapted to the right/left-side comparison technique, the subjective evaluations of the investigator and patients and the results of 20-MHz sonography. Results: There was a more rapid development of beneficial effects with the use of calcipotriol in the initial 8 weeks, although differences in effects were significant only at the time point of therapy week 8 (p < 0.05). After 12 weeks, neither the PASI score nor 20-MHz sonography showed significant differences between the two treatments. While the efficacy of the calcipotriol preparation reached a maximum in the first 4 weeks and then began to subside, the effects of the vitamin B12 cream containing avocado oil remained at a constant level over the whole observation period. This would indicate that the vitamin B12 preparation containing avocado oil may be suitable for use in long-term therapy, a hypothesis further supported by the fact that the investigator and the patients assessed the tolerability of the vitamin B12 cream containing avocado oil as significantly better in comparison with that of calcipotriol. Conclusion: The results of this clinical trial provide evidence that the recently developed vitamin B12 cream containing avocado oil has considerable potential as a well-tolerated, long-term topical therapy of psoriasis.

Stücker, Markus, et al. “Vitamin B12 cream containing avocado oil in the therapy of plaque psoriasis.” Dermatology 203.2 (2001): 141-147. DOI:10.1159/000051729

Relevance of skin tests with drugs in investigating cutaneous adverse drug reactions


Skin tests with drugs can be of value in investigating patients who have developed cutaneous adverse drug reactions (CADR), but their specificity and relevance remain to be determined. A false-positive result on skin testing can happen if it is not compared to results in control subjects. When performing intradermal tests (IDT), we have determined the lowest concentrations that induce false-positive results for many drugs, including betalactam antibiotics, cephalosporins, other antibiotics or non-steroidal anti-inflammatory drugs. Some drugs in their commercialized form contain sodium lauryl sulfate and can induce irritation when patch tested as such. When patch tested with colchicine at 10% in pet. or with a Cytotec® pill (containing misoprostol) at 30% in pet., respectively, 80% of the 29 and 9 of the 10 negative controls developed false-positive results. Lastly, positive results of patch tests with drugs can be related to contact allergy to one of the components of the commercialized form of the drug, without any relevance to the investigation of a CADR, as observed in 2 cases with iodine or avocado oil.

Barbaud, A., et al. “Relevance of skin tests with drugs in investigating cutaneous adverse drug reactions.” Contact Dermatitis 45.5 (2001): 265-268. DOI: 10.1034/j.1600-0536.2001.450502.x

Wet wipes having skin health benefits


A skin health enhancing soft wet wipe or wipe-type product, such as a baby wipe, an adult wipe, hand wipe, a face wipe, a cosmetic wipe, a household wipe, an industrial wipe, a personal cleansing wipe, cotton balls, cotton tipped swabs, and the like, can be made by combining the wipe or wipe-type product with an oil-in-water emulsion composition comprising a natural fat or oil, sterol or sterol derivative, humectant, emulsifying surfactant, and water.

Krzysik, Duane Gerard, et al. “Oil in water emulsion comprising natural fat or oil, sterol, humectant, surfactant, and water; enhances skin barrier; baby or hand wipes.” U.S. Patent No. 6,440,437. 27 Aug. 2002.

Cosmetic oil and composition containing the same


A cosmetic oil comprises a mixture of at least jojoba oil, turnsole oil and a non-saponifiable fraction.

Koulbanis, Constantin, et al. “Jojoba oil, turnsole oil, and non-saponifiable fraction of a vegetable oil for skin.” U.S. Patent No. 4,324,802. 13 Apr. 1982.

Retinol skin care composition


A skin care composition to prevent premature photoaging of the skin of the user includes in addition to basic ingredients, in combination, retinol, a UV absorber and a moisturizer.

Katzev, Phillip K. “Retinol skin care composition.” U.S. Patent No. 5,002,760. 26 Mar. 1991.


Skin treatment preparation


A preparation for treatment of the skin to provide moisture thereto, to promote healing, to maintain a healthy condition; as well as to concurrently produce a pleasing cosmetic effect. The preparation comprises refined mineral oil, apricot kernel oil, avocado oil, aloe vera juice, together with vitamins provided by cod liver oil and preservatives.

Millard, Mary A. “Mineral oils, vegetable oils cod liver oil, propylparaben, butylat.” U.S. Patent No. 4,505,902. 19 Mar. 1985.


The Effect of Various Avocado Oils on Skin Collagen Metabolism


The effects of various avocado oils on collagen metabolism in skin were studied in growing rats fed diets containing 10% (w/w) of the tested oils. Rats fed the unrefined avocado oil extracted with hexane from the intact fruit, its unsaponifiables or the avocado seed oil, showed significant increases in soluble collagen content in skin, though total collagen content was not affected. The increased soluble collagen content appears to be a consequence of the inhibition of lysyl oxidase activity. The active factor was found to be present in the unrefined avocado oil and probably originated from the avocado seed, since collagen metabolism was affected only by fractions which contained lipids fraction from the seed. In comparison rats fed the refined or unrefined soybean oils showed no effects.

Werman, M. J., et al. “The effect of various avocado oils on skin collagen metabolism.” Connective tissue research 26.1-2 (1991): 1-10. DOI:10.3109/03008209109152159


Potential reversal of chronological and photo-aging of the skin by topical application of natural substances


Aging changes in the skin, in which degenerative changes exceed regenerative changes, are characterized by thinning and wrinkling of the epidermis together with the appearance of lines, creases, crevices and furrows, especially accentuated in lines of facial expression. These changes are brought about both by chronological (genetically determined) and photo (solar radiation-determined) factors. The reason for the readily apparent surface morphological alterations is found in changes in the underlying dermis characterized by the loss of fascicular and soluble collagen and elastin fibres, with lessened support of epidermal layers, and lessened circulatory perfusion. Many so-called ‘antiaging’; actions of topically-applied materials are nothing more than transient hydrational/moisturizing effects, which, while lessening the prominence of undesirable surface defects and blemishes, do nothing to change the dermal losses. True ‘antiaging’ actions would require evidence for the return toward normal of the regenerative/degenerative balance exemplified by increased collagen and elastin synthesis. Evidence is accruing that four groups of topically applied substances, namely, (a) nonsaponifiable fractions of avocado and soybean oils, (b) vitamin A derivatives, (c) alpha-hydroxy acids (AHAs), and (d) extracts of Aloe vera, possess activities which reverse the degenerative skin changes seen with aging by stimulating the synthesis of collagen and elastin fibres, thereby restoring toward normal the regenerative/degenerative equilibrium.

Danhof, Ivan E. “Potential reversal of chronological and photo‐aging of the skin by topical application of natural substances.” Phytotherapy Research 7.7 (1993): S53-S56. DOI: 10.1002/ptr.2650070716


Glyceryl Stearate

Instrumental and dermatologist evaluation of the effect of glycerine and urea on dry skin in atopic dermatitis

Background/aims: Moisturising creams are useful treatment adjuncts in inflammatory dermatoses and have beneficial effects in the treatment of dry, scaly skin. The effects on dryness and skin permeability of a new moisturising cream with 20% glycerine was compared with its placebo and with a medicinally authorised cream with 4% urea (combined with 4% sodium chloride) in the treatment of dry skin.

Conclusions: Moisturising creams are different, not only with respect to composition but also with respect to their influence on skin as a barrier to water in patients with atopic dermatitis.


  1. Lodén,A.-C. Andersson,C. Andersson,T. Frödin, H. Öman and M. Lindberg. Skin Research and Technology. Volume 7, Issue 4, pages 209–213, November 2001. DOI: 10.1034/j.1600-0846.2001.70401.x


Cetearyl Alcohol

High incidence of contact dermatitis in leg-ulcer patients–implications for management


A retrospective review of patch test results from all new patients with venous leg ulcers was performed for the preceding 11 months. Eighty one patients referred from general practitioners and district nurses with venous stasis ulcers were included. Positive patch tests were found in 54 patients (67%), including a continued high incidence of allergy to lanolin and topical antibiotics. Multiple allergies were found in 48 patients (58%). In addition, a new problem of allergy to cetearyl alcohol, a constituent of commonly used creams and paste bandages, was identified in 13 patients. There is a continuing high incidence of contact sensitivity in patients with venous stasis ulcers which has important implications for the management of these patients.

Wilson, C. L., et al. “High incidence of contact dermatitis in leg‐ulcer patients–implications for management.” Clinical and experimental dermatology 16.4 (1991): 250-253. DOI: 10.1111/j.1365-2230.1991.tb00368.x

Liquid skin treatment


A composition for the maintenance of smooth, radiant, hydrated skin, including sufficient amounts of acids of hydroxyacid, to facilitate exfoliation of skin in a novel manner, without substantial irritation, as well as the prevention, treatment and management of skin conditions, such as acne, wrinkled, irregularly pigmented, photoaged, and thickened layers of the epidermis, and the like, which has as its constituents, safflower oil, flaxseed oil, sweet almond oil, apricot kernel oil, jojoba oil, organic beeswax, stearic acid, cetearyl alcohol, cocoa butter, vitamin A and tocopheral linoleate, borax, oil of lavender, and tincture of benzoin as an antimicrobial agent.

Harbeck, Marie. “Nonirritating exfoliation for radiant, hydrated skin including safflower oil, flaxseed oil, beeswax, glycol stearate, cetearyl alcohol, cocoa butter, vitamin a, tocopheral linoleate, essential oils, and tincture of benzoin.” U.S. Patent Application No. 09/753,901.

Agents acting against hyperreactive and hypoactive, deficient skin conditions and manifest dermatitides


The invention relates to the use of

  1. a) a compound or several compounds from the group consisting of flavonoids
  2. b) of the antioxidants or
  3. c) of the endogenous energy metabolism metabolites or
  4. d) of the endogenous enzymatic antioxidant systems and synthetic derivatives thereof (mimics) or
  5. e) of the antimicrobial action systems or
  6. f) of the antiviral action systems or
  7. g) active compounds of the known, conventional treatment forms

in each case for the treatment or prophylactic treatment of hyperreactive skin predisposed to dermatitis or deficient, hypoactive skin or dermatoses.

Lanzendorfer, Ghita, Franz Stab, and Sven Untiedt. “Applying to the skin an effective amount of one or more flavonoids.” U.S. Patent No. 5,952,373. 14 Sep. 1999.


Distribution of sunscreens on skin


The effectiveness of sunscreens was originally achieved by incorporation of soluble organic UV absorbers such as cinnamates and others into cosmetic formulations. Determinations of the sun protection factor (SPF) of emulsions containing different organic UV absorbers clearly indicate that the efficacy depends on the absorption characteristics of each single UV filter substance. Nowadays, micronised pigments such as titanium dioxide or zinc oxide have also been found to be protective against harmful UV rays. Our investigations using optical and electron microscopy proved that neither surface characteristics, particle size nor shape of the micronised pigments result in any dermal absorption of this substance. Micronised titanium dioxide is solely deposited on the outermost surface of the stratum corneum and cannot be detected in deeper stratum corneum layers, the human epidermis and dermis.

Schulz, Jens, et al. “Distribution of sunscreens on skin.” Advanced drug delivery reviews 54 (2002): S157-S163. doi:10.1016/S0169-409X(02)00120-5

Topical formulations and transdermal delivery systems containing 1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine


Pharmaceutical formulations and adhesive-coated sheet materials for the topical and/or transdermal delivery of 1-isobutyl-1H-imidazo[4,5-c]-quinolin-4-amine, including creams, ointments and pressure-sensitive adhesive compositions. Pharmacological methods of using the formulations and the adhesive-coated sheet materials of the invention in the treatment of viral infections.

Wick, Steven M., et al. “Viricides comprising isotearic acid; skin disorders.” U.S. Patent No. 5,238,944. 24 Aug. 1993.

Foam skin cream, uses of the foam skin protection cream and a process for its preparation


A foam skin cream can be obtained by

preparing a phase I by melting at 75° C. a mixture containing fatty acids, especially C12-C22 fatty acids, optionally unsaturated and/or polyunsaturated fatty acids, emulsifiers, coemulsifiers, such as triceteareth-4-phosphate, followed by metering it with stirring to

a phase II temperature-controlled at 75° C. obtained from an aqueous mixture containing moisturizers, such as propylene glycol and/or polyhydric alcohols, especially glycerol, emulsifiers, such as alkyl sarcosinates, and skin care additives, such as allantoin;

wherein homogeneous mixing of phases I and II is provided and said metering is performed at a temperature of 75° C.;

after the metered addition, the temperature is maintained at 75° C. for a period of between 5 and 20 minutes; whereupon

the temperature of the thus obtained mixture is lowered to a temperature of between 30 and 40° C. with constant stirring;

the pH value is adjusted to from 7.6 to 8.2, preferably with a skin-compatible basic organic compound, and the mixture obtained is filled into dosage forms with the addition of a propellant.

Neubourg, Fritz. “Foam skin cream, uses of the foam skin protection cream and a process for its preparation.” U.S. Patent No. 6,423,323. 23 Jul. 2002.


Skin mousse


A skin and/or fragrance mousse or foam is provided which is in the form of a light airy stable foam which does not readily break down, and which contains a unique combination of three moisturizers, an alkoxylated methyl glucose derivative such as polypropylene glycol-20 methyl glucose ether, an alkoxylated lanolin derivative such as polyethylene glycol-85 lanolin and acetylated lanolin alcohol.

Moran, Robert P., and Edward P. Carhart Jr. “Skin mousse.” U.S. Patent No. 4,627,973. 9 Dec. 1986.


Skin-care agent for ageing skin


Topical formulations containing one or more compounds chosen from the group (A) consisting of sterols and biochemical precursors thereof in combination with a content of one or more compounds chosen from the group (B) consisting of ubiquinones and derivatives thereof and plastoquinones and derivatives thereof.

Hoppe, Udo, et al. “Skin-care agent for ageing skin.” U.S. Patent No. 6,261,575. 17 Jul. 2001.

Composition for skin care and protection


A composition for topical application to the skin of a human being is disclosed which provides a barrier against irritation and painful damage due to contact with many otherwise harmful materials. The composition comprises in combination water, dimethicone, stearic acid, coconut fatty acid, isopropyl myristate, glycerin, triethanolamine, cetyl alcohol, polyvinyl pyrrolidone, cetearyl alcohol, ceteareth-20, tetrasodium EDTA, hydroxyethyl cellulose, aloe vera gel, vitamin E and lanolin.

Klein, Kenneth. “Composition for skin care and protection.” U.S. Patent No. 5,208,013. 4 May 1993.

Effect of different moisturizers on SLS-irritated human skin


Moisturizers are widely used to treat irritant contact dermatitis (ICD). Their use is, however, not well-documented and standardized models for testing skin care products are needed to acquire documentation of their efficacy. The present study was undertaken to evaluate the effect of 6 commonly-used moisturizers on the recovery of irritated human skin. No commercial interests were involved in the study. 36 healthy volunteers had patch tests with SLS 0.5% applied on their forearms/upper arms for 24 h. After irritation of the skin, all volunteers had a moisturizer applied on one forearm/upper arm, respectively, 3 × daily for the following 5 days. The other forearm/upper arm served as an untreated control. Each moisturizer was tested on 12 volunteers and each volunteer tested 2 moisturizers at the same time. Evaluation was done on days 1, 3 and 8 by transepidermal water loss, electrical capacitance, laser Doppler flowmetry, DermaSpectrometry and clinical scoring. All 6 moisturizers were found to accelerate regeneration of the skin barrier function when compared to irritated non-treated skin. The most lipid-rich moisturizers improved barrier restoration more rapidly than the less lipid-rich moisturizers. We suggest this experimental model for further moisturizer efficacy testing.

Held, Elisabeth, Henrik Lund, and Tove Agner. “Effect of different moisturizers on SLS‐irritated human skin.” Contact dermatitis 44.4 (2001): 229-234. DOI: 10.1034/j.1600-0536.2001.044004229.x


PEG-100 Stearate

PEG-100 Stearate is made by combining natural oils (oftentimes palm or coconut) with Stearic Acid to form a water-soluble ester. It can also be a synthetic polymer made by combining Oxirane (Ethylene Oxide) and fatty acids (source). PEG-100 Stearate is primarily used by the cosmetics and beauty care industry as an emollient, an emulsifier and a moisturizer, although PEG Stearates in general are also known to clean the skin and hair by helping water to mix with oil and dirt so that they can be rinsed away, according to

Unexpected skin barrier influence from nonionic emulsifiers


Skin disorders are often treated with creams containing various active substances. The creams also contain emulsifiers, which are surface-active ingredients used to stabilize the emulsion. Emulsifiers are potential irritants and in the present study the influence of stearic acid, glyceryl stearate, PEG-2, -9, -40, and -100 stearate, steareth-2, -10 and -21 on normal as well as on irritated skin have been evaluated with non-invasive measurements. Test emulsions were created by incorporating 5% emulsifiers in a water/mineral oil mixture (50:50). The emulsions and their vehicle were then applied to normal skin for 48 h and to sodium lauryl sulfate (SLS) damaged skin for 17 h in aluminum chambers. Twenty-four hours after removal of the chambers the test sites were evaluated for degree of irritation. In normal skin, the emulsifiers induced significant differences in TEWL but not in skin blood flow. Five of the emulsifiers increased TEWL. In SLS-damaged skin an aggravation of the irritation was expected. However, no differences regarding skin blood flow was noted from the emulsifiers. Furthermore, three emulsifiers unexpectedly decreased TEWL. These results highlight the possibility of absorption of these emulsifiers into the lipid bilayer, which increase TEWL in normal skin and decrease TEWL in damaged skin.

Ebba Bárány, Magnus Lindberg, Marie Lodén. International Journal of Pharmaceutics. Volume 195, Issues 1–2, 15 February 2000, Pages 189–195. doi:10.1016/S0378-5173(99)00388-9

Influence of hydrophilic surfactants on the properties of multiple W/O/W emulsions


Multiple W/O/W emulsions for topical application using Span 80 as a lipophilic emulsifier were prepared. Several hydrophilic emulsifiers were tested in respect of their suitability for the preparation of multiple emulsions. In addition, the effect of different oil-phase compositions on emulsion stability was investigated. The physicochemical parameters of the formulations were characterized and their long-term stability was evaluated by means of rheological measurements, droplet size observations and conductivity analysis.

As discovered, the modification of an oil-phase composition results in a decrease in the diffusion coefficient of water and water-soluble substances and, consequently, in enhanced stability. The influence of the release of electrolytes from the inner to the outer water phase on the emulsion stability behaviour was investigated. It was found, that the effect of the hydrophilic emulsifiers on the formulation properties is related not only to its HLB value, but rather to its chemical composition.

As a result, polyethoxylated ethers of fatty alcohols (C = 16–18) with HLBs between 15.3 and 16.2 appear to be the most suitable ones for creating stable formulations.

  1. Schmidts, , D. Dobler, C. Nissing, F. Runkel. Journal of Colloid and Interface Science. Volume 338, Issue 1, 1 October 2009, Pages 184–192. doi:10.1016/j.jcis.2009.06.033

Instrumental and dermatologist evaluation of the effect of glycerine and urea on dry skin in atopic dermatitis

M. Lodén, A.-C. Andersson, C. Andersson, T. Frödin, H. Öman and M. Lindberg. Skin Research and Technology. Volume 7, Issue 4, pages 209–213, November 2001. DOI: 10.1034/j.1600-0846.2001.70401.x

Exposure data for cosmetic products: lipstick, body lotion, and face cream


Accurate exposure information for cosmetic products and ingredients is needed in order to conduct safety assessments. Essential information includes both the amount of cosmetic product applied, and the frequency of use. To obtain current data, a study to assess consumer use practices was undertaken. The study included three widely used cosmetic product types: lipstick, body lotion, and face cream. Three hundred and sixty women, ages 19–65 years, who regularly use the products of interest, were recruited at ten different geographical locations within the US. The number of recruits was chosen to ensure a minimum of 300 completes per product type. Subjects were provided with prototype test products, and kept diaries and recorded detailed daily usage information over a two week period. Products were weighed at the start and completion of the study in order to determine the total amount of product used. Statistical analysis of the data was conducted to derive summary distribution of use patterns. The mean and median usage per application, respectively, for the three products was: face cream, 1.22 g and 0.84 g; lipstick, 10 mg and 5 mg; and body lotion, 4.42 g and 3.45 g. The mean and median usage per day for the three products was: face cream, 2.05 g and 1.53 g; lipstick, 24 mg and 13 mg; and body lotion, 8.70 g and 7.63 g. The mean number of applications per day for face cream and lipstick was 1.77 and 2.35, respectively. For body lotion, the mean number of applications per day was dependent on body area, and was 2.12, 1.52, 1.11, 0.95, 0.43, 0.26, and 0.40 for hands, arms, legs, feet, neck and throat, back, and other body areas, respectively. The effect of product preference on use practices was also investigated. This study provides current cosmetic exposure information for commonly used products which will be useful for risk assessment purposes.

L.J. Loretz, A.M. Api, L.M. Barraj, J. Burdick, W.E. Dressler, S.D. Gettings, H. Han Hsu, Y.H.L. Pan, T.A. Re, K.J. Renskers, A. Rothenstein, C.G. Scrafford, C. Sewall. Food and Chemical Toxicology. Volume 43, Issue 2, February 2005, Pages 279–291. doi:10.1016/j.fct.2004.09.016 /

Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial

I. Buraczewska, B. Berne, M. Lindberg, H. Törmä and M. Lodén. British Journal of Dermatology

Volume 156, Issue 3, pages 492–498, March 2007. DOI: 10.1111/j.1365-2133.2006.07685.x

In vitro skin permeation and retention of parabens from cosmetic formulations

S. Pedersen, F. Marra, S. Nicoli and P. Santi. International Journal of Cosmetic Science. Volume 29, Issue 5, pages 361–367, October 2007. DOI: 10.1111/j.1468-2494.2007.00388.x

Percutaneous absorption of parabens from cosmetic formulations

A. DAL POZZO and N. PASTORI. International Journal of Cosmetic Science

Volume 18, Issue 2, pages 57–66, April 1996. DOI: 10.1111/j.1467-2494.1996.tb00135.x


Stearic Acid

Structure/Effect Studies of Fatty Acid Isomers as Skin Penetration Enhancers and Skin Irritants


Comparisons were made of branched vs unbranched saturated fatty acids and cis vs trans unsaturated fatty acids as skin penetration enhancers and primary skin irritants. Skin penetration studies used naloxone base as the diffusant, propylene glycol as the vehicle, and human skin. Maximum naloxone flux was with C9–12-branched and unbranched fatty acids. For C5–14 fatty acids, branched and unbranched isomers had similar effects. One branched C18 fatty acid isomer (C16-branched isostearic acid) was more effective in enhancing skin penetration than a differently branched (C2-branched isostearic acid) or unbranched C18 isomer (stearic acid). There was no significant difference between cis and trans unsaturated C16–18 fatty acid isomers in their effects on naloxone flux, and all unsaturated fatty acids were more effective enhancers than the corresponding saturated isomers. Several of these fatty acid/propylene glycol vehicles were evaluated in a rabbit primary skin irritation test. Irritation indices were poorly correlated with the effectiveness of the vehicles in enhancing naloxone flux. It was possible to enhance naloxone skin penetration greatly with a vehicle with only minimal skin irritation potential.

Aungst, Bruce J. “Structure/effect studies of fatty acid isomers as skin penetration enhancers and skin irritants.” Pharmaceutical research 6.3 (1989): 244-247. DOI 10.1023/A:1015921702258

A comparative study of stearic and lignoceric acid oxidation by human skin fibroblasts


Sensitive assays were developed for long chain and very long chain fatty acid oxidation in human skin fibroblast homogenates. Stearic and lignoceric acids were degraded by the fibroblasts by the β-oxidation pathway. The cofactor requirements for stearic and lignoceric acid β-oxidation were very similar but not identical. For example, appreciable lignoceric acid oxidation could be demonstrated only in the presence of α-cyclodextrin and was inhibited by Triton X-100. In Zellweger’s syndrome, stearic acid β-oxidation was partially reduced whereas lignoceric acid β-oxidation was reduced dramatically (< 12% activity compared to the controls). The results presented suggest that stearic acid β-oxidation occurs in mitochondria as well as in peroxisomes, but lignoceric acid oxidation occurs entirely in the peroxisomes. We suggest that the β-oxidation systems for stearic acid and lignoceric acid may be different.

Singh, Harmeet, and Alf Poulos. “A comparative study of stearic and lignoceric acid oxidation by human skin fibroblasts.” Archives of biochemistry and biophysics 250.1 (1986): 171-179. doi:10.1016/0003-9861(86)90714-9

The contact angle of water on viable human skin


The contact angle of water was measured on clean dry skin and on skin coated with the following materials: paraffin, stearic acid, a lanolin derivative, a quaternary ammonium salt, and hydrophilic and hydrophobic silicones. The area of skin tested was the upper surface of the index finger, which was positioned on the stage of a contact angle telescope goniometer. Clean and degreased skin gave a high contact angle with water (> 100°). All agents studied reduced the water droplet contact angle when applied to the skin. Reductions of contact angles were observed at very low levels of application. Unexpected results were obtained with stearic acid. The water droplet contact angle reduced to a minimum of 70° at 100 μgm stearic acid/cm2 on skin, but further application of stearic acid yielded increasing contact angles to levels from 105° to 120°, depending upon the subject tested.

Ginn, M. E., C. M. Noyes, and Eric Jungermann. “The contact angle of water on viable human skin.” Journal of colloid and interface science 26.2 (1968): 146-151. doi:10.1016/0021-9797(68)90306-8

Increased Synthesis of Hexacosanoic Acid (C26 :0) by Cultured Skin Fibroblasts from Patients with Adrenoleukodystrophy (ALD) and Adrenomyeloneuropathy (AMN)1


We studied the metabolism of radioactive stearic acid by cultured skin fibroblasts from patients with adrenoleukodystrophy (ALD) and its variant, adrenomyeloneuropathy (AMN), to clarify the mechanism of the increased content of very long chain saturated fatty acids in cholesterol esters and sphirigolipids, which are known to be the characteristic biochemical changes in ALD and AMN. A substantial amount of hexacosanoic acid (C26 : 0) was synthesized from stearic acid by ALD and AMN fibroblasts, whereas only a trace amount of hexacosanoic acid was synthesized by control fibroblasts. This indicates that the primary biochemical defect in ALD and AMN may involve the elongation system of very long chain fatty acids.

Tsuji, Shoji, et al. “Increased synthesis of hexacosanoic acid (C26: 0) by cultured skin fibroblasts from patients with adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN).” Journal of biochemistry 90.4 (1981): 1233-1236.

An electron spin resonance study of skin penetration enhancers


The structured intercellular lipids of the stratum corneum are thought to play an important role in controlling the transport of drugs across the skin. In this study, multilamellar dipalmitoylphosphatidylcholine liposomes were used as a model of structured lipids. The effect of temperature and skin penetration enhancers on the lipid bilayer, was assessed using a spin labelling technique, in which 5-doxyl stearic acid was incorporated into the bilayer. The order parameter (S) of the spin label was calculated from the observed spectra. An increase in temperature decreased the order parameter. This decrease is due to increased rotational movement of the acyl chain of the spin label about its long molecular axis. It indicates a decrease in order within the bilayer structure, as a result of increased flexibility of the lipid molecules. Known skin penetration enhancers, Brij 36T, n-decylmethyl sulphoxide and oleic acid, also decreased the order parameter of the spin label. The penetration enhancer N-methyl-2-pyrrolidone had no significant effect. The results obtained were confirmed using a light scattering technique, in which the phase transition temperature of the liposomes was monitored in the presence and absence of the enhancers. 5-Doxyl stearic acid was incorporated into stratum corneum, separated from human cadaver skin. The spectra obtained were similar to those of the liposomal samples and the application of n-decylmethyl sulphoxide had a similar effect on the order parameter.

Cosmetic preparation


A cosmetic preparation is disclosed which is effective in moisturizing and softening skin, improving texture and feel of skin, and diminishing superficial and deep wrinkles in skin. The preparation comprises gibberellic acid and lysine as active ingredients. The preparation can contain as additional active ingredients gliadin, ascorbic acid and urea.

Parkinson, Richard W. “Gibberellic acid, lysine, skin softener.” U.S. Patent No. 4,518,614. 21 May 1985.

Cleansing without compromise: the impact of cleansers on the skin barrier and the technology of mild cleansing


Cleanser technology has come a long way from merely cleansing to providing mildness and moisturizing benefits as well. It is known that harsh surfactants in cleansers can cause damage to skin proteins and lipids, leading to after-wash tightness, dryness, barrier damage, irritation, and even itch. In order for cleansers to provide skin-care benefits, they first must minimize surfactant damage to skin proteins and lipids. Secondly, they must deposit and deliver beneficial agents such as occlusives, skin lipids, and humectants under wash conditions to improve skin hydration, as well as mechanical and visual properties. While all surfactants tend to interact to some degree with lipids, their interaction with proteins can vary significantly, depending upon the nature of their functional head group. In vitro, ex vivo, and in vivo studies have shown that surfactants that cause significant skin irritation interact strongly with skin proteins. Based on this understanding, several surfactants and surfactant mixtures have been identified as “less irritating” mild surfactants because of their diminished interactions with skin proteins. Surfactants that interact minimally with both skin lipids and proteins are especially mild. Another factor that can aggravate surfactant-induced dryness and irritation is the pH of the cleanser. The present authors’ recent studies demonstrate that high pH (pH 10) solutions, even in the absence of surfactants, can increase stratum corneum (SC) swelling and alter lipid rigidity, thereby suggesting that cleansers with neutral or acidic pH, close to SC-normal pH 5.5, may be potentially less damaging to the skin. Mildness enhancers and moisturizing agents such as lipids, occlusives, and humectants minimize damaging interactions between surfactants, and skin proteins and lipids, and thereby, reduce skin damage. In addition, these agents play an ameliorative role, replenishing the skin lipids lost during the wash period. The present review discusses the benefits of such agents and their respective roles in improving the overall health of the skin barrier.


Dietary trans fatty acids increase conjugated linoleic acid levels in human serum


Conjugated linoleic acid (CLA), fatty acids with 18 carbon atoms and two conjugated cis/trans double bonds, have shown anticarcinogenic effects in experimental studies. We determined the proportion of CLA (the sum of cis-9, trans-11 and trans-9, cis-11 CLA) of total fatty acids in the diets and serum samples of healthy subjects who consumed for 5 weeks a diet high in saturated fatty acids mainly from dairy fat, followed by 5 weeks on a diet high (8.7% of energy, en%) in trans fatty acids from partially hydrogenated vegetable oil (40 subjects) or a similar diet high in stearic acid (9.3 en%, 40 subjects). All diets contained equal amounts of fat and cis-monounsaturated and cis-polyunsaturated fatty acids. The fatty acid compositions of the pooled diets and fasting serum samples drawn at the end of the diet periods were analyzed by gas chromatography, and CLA was identified by comparison with a standard of C18:2 conjugated dienes. The proportions of CLA in the dairy fat, trans fatty acid, and stearic acid diets were 0.37, 0.04, and 0.10% of total methylated fatty acids, respectively. The corresponding mean (SD) proportions in serum were 0.33 (0.07)% after the dairy fat diet, higher, 0.43 (0.12)%, P < 0.001, after the trans fatty acid diet, and lower, 0.17 (0.06)%, P < 0.001, after the stearic acid diet. The difference between dairy fat and stearic acid diets was explained by different dietary intakes but increased amounts of CLA not present in the diet were incorporated into serum lipids during the trans fatty acid diet. CLA in human tissues is partly derived from the diet but part of it may be formed by conversion from dietary trans fatty acids.

Salminen, Irma, et al. “Dietary trans fatty acids increase conjugated linoleic acid levels in human serum.” The Journal of Nutritional Biochemistry 9.2 (1998): 93-98. doi:10.1016/S0955-2863(97)00173-3


Conversions of palmitic and stearic acid in the intact rat


  1. Labeled stearic acid injected as the albumin complex is extensively desaturated in the liver of carbohydrate-refed rats: one half of liver “stearic isotope” is recovered as oleic acid.
  2. A smaller portion of labeled palmitic acid is desaturated to palmitoleic acid, but comparable amounts of label are also found in stearic and octadecenoic acid.
  3. The liver octadecenoic acid label derived from palmitic acid is found mainly in oleic acid, but particularly in the phospholipids an appreciable fraction is found in cis-vaccenic acid. Liver phospholipids also contain more unlabeled cis-vaccenic acid than do liver neutral fat and adipose tissue total fat.
  4. In extrahepatic tissues, including subcutaneous adipose tissue, desaturation and elongation are less prominent than in liver.
  5. Fasting abolishes desaturation of both stearic and palmitic acid completely and elongation of palmitic acid almost completely.
  6. In the tissues fatty acids appear to be metabolized in the same manner, whether they be formed in situ by conversion of other acids or are taken up as such from the blood.

Elovson, J. “Conversions of palmitic and stearic acid in the intact rat.” Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism 106.2 (1965): 291-303. doi:10.1016/0005-2760(65)90037-8


A comparative study of straight chain and branched chain fatty acid oxidation in skin fibroblasts from patients with peroxisomal disorders.


The beta-oxidation of stearic acid and of alpha- and gamma-methyl isoprenoid-derived fatty acids (pristanic and tetramethylheptadecanoic acids, respectively) was investigated in normal skin fibroblasts and in fibroblasts from patients with inherited defects in peroxisomal biogenesis. Stearic acid beta-oxidation by normal fibroblast homogenates was several-fold greater compared to the oxidation of the two branched chain fatty acids. The effect of phosphatidylcholine, alpha-cyclodextrin, and bovine serum albumin on the three activities suggests that different enzymes are involved in the beta-oxidation of straight chain and branched chain fatty acids. Homogenates of fibroblasts from patients with a deficiency in peroxisomes (Zellweger syndrome and infantile Refsum’s disease) showed a normal ability to beta-oxidize stearic acid, but the oxidation of pristanic and tetramethylheptadecanoic acid was decreased. Concomitantly, 14CO2 production from the branched chain fatty acids by Zellweger fibroblasts in culture (but not from stearic acid) was greatly diminished. The Zellweger fibroblasts also showed a marked reduction in the amount of water-soluble metabolites from the radiolabeled branched chain fatty acids that are released into the culture medium. The data presented indicate that the oxidation of alpha- and gamma-methyl isoprenoid-derived fatty acids takes place largely in peroxisomes in human skin fibroblasts.

Singh, Harmeet, et al. “A comparative study of straight chain and branched chain fatty acid oxidation in skin fibroblasts from patients with peroxisomal disorders.” Journal of lipid research 31.2 (1990): 217-225.

Xanthan Gum

Xanthan gum: production, recovery, and properties


Xanthan gum is a microbial polysaccharide of great commercial significance. This review focuses on various aspects of xanthan production, including the producing organismXanthomonas campestris, the kinetics of growth and production, the downstream recovery of the polysaccharide, and the solution properties of xanthan.

F Garcı́a-Ochoa, V.E Santos, J.A Casas, E Gómez Biotechnology Advances Volume 18, Issue 7, 1 November 2000, Pages 549–579. doi:10.1016/S0734-9750(00)00050-1

Antioxidative properties of xanthan on the autoxidation of soybean oil in cyclodextrin emulsion.

Antioxidative properties of xanthan on the autoxidation of soybean oil in cyclodextrin emulsion. Kazuko. Shimada , Kuniko. Fujikawa , Keiko. Yahara , Takashi. Nakamura. J. Agric. Food Chem., 1992, 40 (6), pp 945–948. DOI: 10.1021/jf00018a005

Xanthan gum biosynthesis and application: a biochemical /genetic perspective


Xanthan gum is a complex exopolysaccharide produced by the plant-pathogenic bacteriumXanthomonas campestris pv. campestris. It consists of D-glucosyl, D-mannosyl, and D-glucuronyl acid residues in a molar ratio of 2:2:1 and variable proportions of O-acetyl and pyruvyl residues. Because of its physical properties, it is widely used as a thickener or viscosifier in both food and non-food industries. Xanthan gum is also used as a stabilizer for a wide variety of suspensions, emulsions, and foams. This article outlines aspects of the biochemical assembly and genetic loci involved in its biosynthesis, including the synthesis of the sugar nucleotide substrates, the building and decoration of the pentasaccharide subunit, and the polymerization and secretion of the polymer. An overview of the applications and industrial production of xanthan is also covered.

Xanthan gum biosynthesis and application: a biochemical /genetic perspective. A. Becker,F. Katzen, A. Pühler, L. Ielpi. Applied Microbiology and Biotechnology. August 1998, Volume 50, Issue 2, pp 145-152.

Intermolecular binding of xanthan gum and carob gum


Gels are a representative state for polysaccharides in both natural and artificial systems. The nature of the inter-chain associations within the junction zones is important and models for such interactions between like polysaccharides are based on X-ray diffraction studies of oriented gels. Here we describe the extension of such studies to a binary gel (xanthan-carob) in order to characterize for the first time intermolecular binding between different polysaccharides. Xanthan-carob binding has been proposed to explain gelation of the mixtures and as a model for host-pathogen recognition and adhesion of Xanthomonas bacteria within plant vascular systems. Our data suggest that the established model1–7 is incorrect and point to an alternative association mechanism.

Intermolecular binding of xanthan gum and carob gum. P. CAIRNS, M. J. MILES & V. J. MORRIS. Nature 322, 89 – 90 (03 July 1986); doi:10.1038/322089a0


Comparative study on xanthan gum and hydroxypropylmethyl cellulose as matrices for controlled-release drug delivery I. Compaction and in vitro drug release behaviour..


A comparative investigation has been undertaken to assess the performance of xanthan gum (XG) and hydroxypropylmethyl cellulose (HPMC) as hydrophilic matrix-forming agents in respect of compaction characteristics and in vitro drug release behaviour. The overall compaction characteristics are found to be quite similar to each other and typical of polymer behaviour. But the flow characteristics are different, i.e., XG is more readily flowable than HPMC. The observed difference in drug release profiles between these two potential excipients are explored and explained by the difference in their hydrophilicity and subsequent hydration properties.

Comparative study on xanthan gum and hydroxypropylmethyl cellulose as matrices for controlled-release drug delivery I. Compaction and in vitro drug release behaviour. Mohammad Mahiuddin Talukdar, Armand Michoel, Patrick Rombaut, Renaat Kinget. International Journal of Pharmaceutics.Volume 129, Issues 1–2, 8 March 1996, Pages 233–241. doi:10.1016/0378-5173(95)04355-1






Quantitative and qualitative changes in dermal collagen and elastin occur in response to chronic ultraviolet (UV) irradiation. These changes have been implicated in the genesis of the wrinkling seen in chronically irradiated, or photoaged skin. We examined the relationship between wrinkle formation and changes in dermal structural protein content and type. Skh-1 hairless mice were irradiated with suberythemal doses of UV-B three times a week for up to 20 wk. Visible wrinkling was present after 6–7 wk of irradiation. Dermal elastic fiber content was quantified by color image analysis of paraffin-embedded tissue. There was no significant difference in dermal elastic fiber content between irradiated and age-matched control mice after either 10 or 20 wk of irradiation. The effect of UV-B irradiation on total dermal collagen content, ratio of collagen type III-type I, and extent of glycosylation and crosslinking of collagen was no different in irradiated and age-matched control mice after 10 wk of irradiation. Increased epidermal thickness was evident in frozen sections after 6 wk of irradiation, and the thickness increased with continued irradiation. Dermal thickening was evident after 10 wk of irradiation. Sufficient UV-B irradiation will eventually cause changes in dermal elastin and collagen content; however, wrinkle formation precedes such changes. A causal relationship between wrinkle formation and dermal structural protein content changes in Skh-1 hairless mice could not be established in this study.

Moloney, Stephen J., et al. “The hairless mouse model of photoaging: evaluation of the relationship between dermal elastin, collagen, skin thickness and wrinkles.” Photochemistry and photobiology 56.4 (1992): 505-511. DOI: 10.1111/j.1751-1097.1992.tb02194.x


Aspartic acid racemization: evidence for marked longevity of elastin in human skin


Background  In extracellular proteins, aspartic acid racemization (AAR) has the potential to identify long-lived or permanent proteins.

Objectives  We present data to show an age-dependent increase in AAR in chronologically aged skin elastin.

Methods  Elastin was purified in a multistep procedure designed to remove contaminating proteins and to avoid induced racemization. As a control experiment, elastin was also purified from the richest elastin bearing tissue, the yellow ligaments of the spine.

Results  In total skin, specimens displayed a slight age-dependent increase in d-aspartyl residues, but in purified elastin the rate of increase was rapid and highly correlated with age (r = 0·98). Similar rates were observed in the control data from the yellow ligaments. The AAR rates were found to be higher in elastin from skin (and yellow ligaments) than previous studies of lung parenchyma and from aorta had shown. These differences appear to be related to the purity of the extracted elastin product, and to a significant in vivo degradation of elastin in skin.

Conclusions  The age-dependent accumulation of modified aspartic acid residues appears to be a common feature in ageing elastin, independent of the tissue source. This indicates a lack of turnover and an accumulation of elastin damage in diverse ageing tissues, possibly as part of programmed ageing.

Aspartic acid racemization: evidence for marked longevity of elastin in human skin.

Ritz‐Timme, Stefanie, I. Laumeier, and Matthew J. Collins. “Aspartic acid racemization: evidence for marked longevity of elastin in human skin.” British Journal of Dermatology 149.5 (2003): 951-959. DOI: 10.1111/j.1365-2133.2003.05618.x


Determination of desmosines in elastin-related skin disorders by isocratic high-performance liquid chromatography


Abnormalities in the amount of skin elastin occur in several cutaneous disorders. The number of elastic fibers is increased in elastotic disorders such as pseudoxanthoma elasticum (PXE) and cutis rhomboidalis nuchae (actinic elastosis, AE) and is decreased in elastolytic disorders such as cutis laxa (CL). We describe a procedure to quantify desmosines and elastin in small amounts of skin using high-performance liquid chromatography (HPLC). Biopsies were obtained from normal, nonsolar exposed skin and from the lesional skin of patients with PXE, cutis rhomboidalis nuchae, and CL. Specimens were subjected to hot alkali treatment and the desmosines were released by acid hydrolysis and quantified by HPLC. The mean value for normal skin was 252 ± 28 ng desmosines per milligram wet weight (SD, n = 5). The disorders of elastosis (PXE and AE) demonstrated a two-to fivefold increased content of desmosines. In contrast, the elastolytic disorder (CL) had only 20% of the normal content of esmosines. Furthermore, PXE and normal skin elastins had the same amount of desmosines per milligram purified elastin. This method could be used to evaluate the extent of elastosis or elastolysis in a particular lesion.

Schwartz, Elaine, Frederick A. Cruickshank, and Mark Lebwohl. “Determination of desmosines in elastin-related skin disorders by isocratic high-performance liquid chromatography.” Experimental and molecular pathology 52.1 (1990): 63-68. doi:10.1016/0014-4800(90)90059-M


Molecular basis of sun-induced premature skin ageing and retinoid antagonism


DAMAGE to skin collagen and elastin (extracellular matrix) is the hallmark of long-term exposure to solar ultraviolet irradiation(1-3), and is believed to be responsible for the wrinkled appearance of sun-exposed skin(4,5). We report here that matrix-degrading metalloproteinase messenger RNAs, proteins and activities are induced in human skin in vivo within hours of exposure to ultraviolet-B irradiation (UVB). Induction of metalloproteinase proteins and activities occurred at UVB doses well below those that cause skin reddening. Within minutes, low-dose UVB upregulated the transcription factors AP-1 and NF-kappa B, which are known to be stimulators of metalloproteinase genes(6,7). All-trans retinoic acid, which transrepresses AP-1 (ref. 8), applied before irradiation with UVB, substantially reduced AP-1 and metalloproteinase induction, We propose that elevated metalloproteinases, resulting from activation of AP-1 and NF-kappa B by low dose solar irradiation, degrade collagen and elastin in skin, Such damage, if imperfectly repaired would result in solar scars, which through accumulation from a lifetime of repeated low-dose sunlight exposure could cause premature skin ageing (photoageing).

Fisher, Gary J., et al. “Molecular basis of sun-induced premature skin ageing and retinoid antagonism.” (1996).


A monoclonal antibody (Mab 67) marks type B synoviocytes


The functionally important lining cells of the synovium (types A and B synoviocytes) are the subjects of much study but have presented problems with their characterization and microscopical identification, particularly at the light level. Type A (macrophage-like) synoviocytes, however are more easily localized than the type B (fibroblast-like) variety because of the greater availability of antimacrophage antisera. We describe, using light and electron microscopy, a monoclonal antibody which in the synovial intimal layer is specific for type B synoviocytes.

Stevens, C. R., P. I. Mapp, and P. A. Revell. “A monoclonal antibody (Mab 67) marks type B synoviocytes.” Rheumatology international 10.3 (1990): 103-106. DOI



The role of elastin in the mechanical properties of skin


The elastin fibers of rat skin samples were degraded by the use of a purified preparation of elastase to which soybean inhibitor was added, preventing the collagenolytic activity of the elastase on collagen. Control experiments ascertained degradation of elastin and no effect on collagen. The mechanical properties of the skin samples were studied before and after the enzymatic treatment and differences ascribed to the degraded elastin fibers. Elastin plays a role in the mechanical behaviour of rat skin at small stress values and small deformations. Especially, the elastin fibers are responsible for the recoiling mechanism after a stress or deformation has been applied.

Oxlund, Hans, Jan Manschot, and A. Viidik. “The role of elastin in the mechanical properties of skin.” Journal of biomechanics 21.3 (1988): 213-218. doi:10.1016/0021-9290(88)90172-8


Transforming growth factor-beta up-regulates elastin gene expression in human skin fibroblasts. Evidence for post-transcriptional modulation.


Transforming growth factor-beta s (TGF-beta) are potent enhancers of the expression of several connective tissue genes. In this study we examined the effects of TGF-beta 1 and TGF-beta 2 on human elastin mRNA abundance, promoter activity, and mRNA stability in cultured human skin fibroblasts. Treatment of cell cultures with varying concentrations of TGF-beta 1 or TGF-beta 2 for 24 hours resulted in a dose-dependent increase in the elastin mRNA steady-state levels, with a maximum enhancement of approximately 30-fold being noted with 1 ng/ml. Addition of cycloheximide (10 micrograms/ml) failed to block up-regulation of elastin gene expression by TGF-beta, indicating that this effect can occur in the absence of active protein synthesis. Furthermore, TGF-beta elicited enhancement of elastin mRNA levels could be abrogated by tumor necrosis factor-alpha and partially counteracted by interferon-gamma. Transient transfections of human skin fibroblasts with elastin promoter/chloramphenicol acetyl-transferase reporter gene constructs, which contained up to approximately 5 kb of the 5′ flanking DNA, revealed no change in the promoter activity in the presence of TGF-beta. However, TGF-beta appeared to stabilize the elastin mRNA transcripts as determined by Northern hybridizations after inhibition of initiation of the transcription. As a result of this stabilization, the elastin mRNA levels were clearly detectable in TGF-beta 1-treated cultures even up to 48 hours after inhibition of transcription while they were undetectable in the control cells after 24 hours of incubation. These results demonstrate that TGF-beta 1 and TGF-beta 2 are potent enhancers of elastin gene expression and that this effect is mediated, at least in part, post-transcriptionally. These results suggest that TGF-beta s are involved in regulation of elastin deposition during fetal development and tissue repair, as well as in pathological conditions.


Connective tissue nevi of the skin: Clinical, genetic, and histopathologic classification of hamartomas of the collagen, elastin, and proteoglycan type


Connective tissue nevi of the skin are hamartomatous lesions consisting predominantly of one of the components of the extracellular matrix, namely, collagen, elastin, or glycosaminoglycans. On the basis of clinical, histopathologic, and genetic considerations, the connective tissue nevi can be classified into defined categories. Association with extracutaneous features allows further delineation of these disease entities and aids in establishing an accurate diagnosis.

Uitto, Jouni, Daniel J. Santa Cruz, and Arthur Z. Eisen. “Connective tissue nevi of the skin: clinical, genetic, and histopathologic classification of hamartomas of the collagen, elastin, and proteoglycan type.” Journal of the American Academy of Dermatology 3.5 (1980): 441-461. doi:10.1016/S0190-9622(80)80106-X


Extracellular matrix characterization during healing of full-thickness wounds treated with a collagen/elastin dermal substitute shows improved skin regeneration in pigs.


We investigated the architecture of the extracellular matrix (ECM) during healing of full-thickness wounds in the pig. Two different treatments, one based on epidermal transplantation (split skin mesh grafts, SP wounds) and one consisting of a combination of epidermal transplantation and a dermal matrix substitute (MA wounds) were compared. The dermal matrix consisted of native bovine collagen coated with elastin hydrolysate. The latter treatment reduced wound contraction and improved tissue regeneration. The expression patterns of fibronectin, von Willebrand factor, laminin, chondroitin sulfate, and elastin, detected by immunohistochemistry, were examined in time and indicated different stages of healing. During the early phase of healing the dermal matrix induced more granulation tissue, a different fibronectin expression pattern, and rapid vascular cell ingrowth (von Willebrand factor). Furthermore, in the MA wounds chondroitin sulfate was detected earlier in the basement membrane and fibronectin staining disappeared more rapidly. During later stages of healing, chondroitin sulfate expression was selective for areas in which ECM remodeling was active; in these specific areas elastin staining reappeared. ECM remodeling and elastin regeneration occurred both in the upper and lower dermis for the MA wounds but only in the upper dermis for the SP wounds. Electron microscopic evaluation of the wounds after 2 weeks showed many myofibroblasts in the SP wounds, whereas in the MA wounds cells associated with the dermal matrix had characteristics of normal fibroblasts. The results suggest that the biodegradable dermal matrix served as a template for dermal tissue regeneration, allowed faster regeneration, and improved the quality of healing in large full-thickness skin defects.

Lamme, Evert N., et al. “Extracellular matrix characterization during healing of full-thickness wounds treated with a collagen/elastin dermal substitute shows improved skin regeneration in pigs.” Journal of Histochemistry & Cytochemistry 44.11 (1996): 1311-1322. doi: 10.1177/44.11.8918906


Potassium Sorbate

Effect of potassium sorbate washing on the growth of Listeria monocytogenes on fresh poultry


This work evaluated the effect of potassium sorbate washing on the growth of Listeria monocytogenes on poultry legs stored at 4 °C for 7 days. Fresh inoculated chicken legs were dipped into either a 2.5% (w/v) or 5% potassium sorbate solution or distilled water (control). Changes in mesophiles, pychrotrophic counts and sensorial characteristics (odor, color, texture and overall appearance) were also evaluated.

The shelf life of the samples washed with potassium sorbate was extended by at least 2 days over the control samples washed with distilled water. Legs washed with 5% potassium sorbate showed a significant (p < 0.05) inhibitory effect on L. monocytogenes compared to control legs, with a decrease of about 1.3 log units after 7 days of storage. Sensory quality was not adversely affected by potassium sorbate.

González-Fandos, E., and J. L. Dominguez. “Effect of potassium sorbate washing on the growth of Listeria monocytogenes on fresh poultry.” Food Control 18.7 (2007): 842-846. doi:10.1016/j.foodcont.2006.04.008

Potassium Sorbate Diffusivity in American Processed and Mozzarella Cheeses


The diffusivity of potassium sorbate in cheeses was determined by using diffusion models and computer programming for examining the residual surface concentration and the penetration of surface-applied potassium sorbate into cheese. To determine diffusivity, the concentration of potassium sorbate in sliced cheese was measured by penetration time and distance from surface. The diffusivity was calculated by nonlinear regression with experimental data based on Fick’s law. The diffusivity of potassium sorbate through American processed cheese was 1.31∞10-6 cm2/sec and for Mozzarella cheese 6.74∞10-7 cm2/sec. This indicated that Mozzarella cheese would maintain surface concentration of potassium sorbate above the critical fungistatic level two times longer than American processed cheese.

Han, Jung Hoon, and John D. Floros. “Potassium sorbate diffusivity in American processed and Mozzarella cheeses.” Journal of food science 63.3 (1998): 435-437. DOI: 10.1111/j.1365-2621.1998.tb15758.x

Food applications of sorbic acid and its salts


Because of their physiological inertness, their effectiveness even in the weakly acid pH range and their neutral taste, sorbic acid and its salts have become the leading preservatives in the food sector throughout the world over the past 30 years. The most commonly used products are sorbic acid itself (E200) and potassium sorbate (E202). In many countries sodium sorbate (E201) and calcium sorbate (E203) are also permitted. Sorbic acid is sparingly soluble in water, sodium sorbate has better solubility, and potassium sorbate is very freely soluble and can be used to produce 50% stock solutions. The soluble sorbates are preferred when it is desired to use the preservative in liquid form, or when aqueous systems are to be preserved. Sodium sorbate in solid form is unstable and very rapidly undergoes oxidation on exposure to atmospheric oxygen. It is therefore not produced on the industrial scale. Aqueous solutions of sodium sorbate remain stable for some time. Calcium sorbate is used in the manufacture of fungistatic wrappers because it is highly stable to oxidation, but this use is very limited. Sorbic acid and sorbates can be directly added into the product. The products can be dipped or sprayed with aqueous solutions of sorbates. Dusting of food with dry sorbic acid is also possible but less recommended because sorbic acid irritates the skin and mucous membranes. Sorbic acid and particularly calcium sorbate can be used as active substances in fungistatic wrappers. A general survey of the numerous uses of sorbic acid in the food sector will be given. Some fields of application will be discussed that are either unimportant or not permitted in the U.K.

Lück, E. “Food applications of sorbic acid and its salts.” Food Additives & Contaminants 7.5 (1990): 711-715. DOI:10.1080/02652039009373936

Extending Shelf-Life of Fresh Wet Red Hake and Salmon Using CO2-O2 Modified Atmosphere and Potassium Sorbate Ice at 1°C


The ability to safely extend the shelf-life of fish would open up the possibility of shipping fresh wet fish by boat. Red hake and salmon can be successfully held for almost 1 month and still be sensorally acceptable. A 60% carbon dioxide:20% oxygen:20% nitrogen-modified atmosphere with a 1% potassium sorbate ice was most satisfactory. CO2 did not lower the pH of the fish. Low temperature (1°C) and presence of both oxygen and potassium sorbate served as protection against botulism development. The presence of oxygen, even with salmon, did not lead to rancidity (TBA) problems. The Torrymeter can be used to monitor red hake quality. Work incorporating potassium sorbate dips before modified atmosphere storage with or without potassium sorbate ice is needed.

Fey, M. S., and J. M. Regenstein. “Extending Shelf‐Life of Fresh Wet Red Hake and Salmon Using CO2‐O2 Modified Atmosphere and Potassium Sorbate Ice at 1° C.” Journal of Food Science 47.4 (1982): 1048-1054. DOI: 10.1111/j.1365-2621.1982.tb07619.x



The individual and combined antilisterial activity of the preservatives sodium lactate (4%), potassium sorbate (0.3%) and nisin (400 IU/ml), in either the presence or absence of the curing salts nitrite (125 ppm) and polyphosphate (0.5%), was assessed in buffered BHI broth (pH 5.5) during incubation at 4C. A cocktail of the strain Listeria monocytogenes NCTC 7973 and two food derived strains was used as the inoculum in challenge studies. In the absence of the preservatives, L. monocytogenes grew in the presence of polyphosphate but not in the presence of nitrite or a combination of nitrite and polyphosphate. The antilisterial action of nitrite was predominantly bacteriostatic in nature. Lactate acting alone, or in the presence of curing salts, produced a bacteriostatic effect. Sorbate acting alone had a bacteriostatic effect. Sorbate acting in the presence of nitrite or nitrite and polyphosphate produced a marked listericidal effect, reducing the population by 6.7 logs and 5.4 logs, respectively. Nisin acting alone produced an almost immediate 90% listericidal response (1 log population decrease), but initial numbers were restored within 14 days by regrowth. Regrowth was eliminated when nisin was used in combination with lactate, nitrite or nitrite and polyphosphate. The combination of lactate and sorbate offered no advantage over the use of sorbate alone. Sorbate and nisin acting in combination produced an enhanced listericidal effect, which was also seen in the presence of curing salts, but was delayed. No listericidal advantage over sorbate-nisin combination was achieved through the use of the lactate-sorbate-nisin combination. The combined use of sorbate and nisin offers promise as a means of eliminating L. monocytogenes from low pH cured meat products. The efficacy of this preservative combination remains to be evaluated in a meat system before its practical application can be considered.

Buncic, S., et al. “Individual and combined listericidal effects of sodium lactate, potassium sorbate, nisin and curing salts at refrigeration temperature.” Journal of Food Safety 15.3 (1995): 247-264. DOI: 10.1111/j.1745-4565.1995.tb00137.x



Fresh, broiler parts were dipped 30 or 60 set in solutions of potassium sorbate. Drumsticks were stored at refrigerator temperature and evaluated daily for off-odor development and total counts. Thighs and breasts were baked to internal breast temperature of 85°C cooled, then evaluated for shear press values, moisture retention, and sensory properties. Drumsticks dipped in potassium sorbate developed off-odors later than the controls. Those parts dipped in 10% potassium sorbate had a 20-day shelf-life at 4°C, based on off-odor development and time for total counts to reach 10′. Parts dipped i

n potassium sorbate for 30 set, drained, then baked had similar Shear Press (tenderness) and Carver Press (moisture retention) values regardless of the sorbate concentration used. Taste panel members could not distinguish between those parts dipped in 5 or 10% potassium sorbate and those parts dipped in distilled water. Sensory evaluations were significantly lower for those parts dipped in 15% potassium sorbate solutions for 1 mm. Parts dipped in 5 or 10% solutions for 1 mm were indistinguishable from the controls.

Cunningham, F. E. “Shelf‐life and quality characteristics of poultry parts dipped in potassium sorbate.” Journal of Food Science 44.3 (1979): 863-864. DOI: 10.1111/j.1365-2621.1979.tb08522.x

Effects of Cetylpyridinium Chloride, Acidified Sodium Chlorite, and Potassium Sorbate on Populations of Escherichia coli O157:H7, Listeria monocytogenes, and Staphylococcus aureus on Fresh Beef


The effects of selected food-grade antimicrobial agents at decreasing the number of pathogenic bacteria on fresh beef were determined. Beef cubes inoculated with Escherichia coli O157:H7, Listeria monocytogenes, or Staphylococcus aureus were sprayed with 0.5% cetylpyridinium chloride (CPC), 0.12% acidified sodium chlorite (ASC), 0.1% potassium sorbate (PS), or an equal mix of any two solutions. The beef samples were placed on absorbent tray pads sprayed with each single or mixed solution, wrapped with polyvinyl chloride film, heat sealed, and stored at 4°C for 2 weeks. Surface sanitization using CPC, ASC, or an equal mix of these two agents effectively reduced microbial numbers on the beef during storage. At day 0, ASC and the CPC-ASC mix reduced the number of E. coli O157:H7 by 2.50 and 1.58 log CFU/cm2, respectively. CPC demonstrated a 3.25-log reduction of L. monocytogenes and a 4.70-log reduction of S. aureus at 14 days. The CPC-PS mix reduced E. coli O157:H7 numbers by 1.46, L. monocytogenes by 2.95, and S. aureus by 4.41 log CFU/cm2 at 14 days. PS alone and the mixed solutions, CPC-ASC, CPC-PS, or ASC-PS, were not as effective as ASC or CPC alone. To effectively reduce E. coli O157:H7, L. monocytogenes, or S. aureus numbers, higher (>0.1%) concentrations of PS were necessary. Loss of redness and light color of beef surfaces consistently coincided with decreases in pH for ASC-treated beef samples.

Lim, Kyungwha, and Azlin Mustapha. “Effects of cetylpyridinium chloride, acidified sodium chlorite, and potassium sorbate on populations of Escherichia coli O157: H7, Listeria monocytogenes, and Staphylococcus aureus on fresh beef.” Journal of Food Protection® 67.2 (2004): 310-315.

Sorbic Acid and Potassium Sorbate Permeability of an Edible Methylcellulose-Palmitic Acid Film: Water Activity and pH Effects


The apparent permeability constants for potassium sorbate and sorbic acid through an edible film composed of methylcellulose and palmitic acid (weight ratio 3:1) were evaluated as a function of water activity (aw) and pH. For films with thickness 55–66 μm, potassium sorbate permeability increased from 2.3 × 10−10 to 2.0 × 10−8 (mg/sec cm2)(cm)/(mg/mL) as aw increased from 0.65 to 0.80. Films were not stable at aw levels above 0.80. Permeability of the film to sorbic acid at aw 0.8 decreased from 3.3 × 10−8 to 9.1 × 10−10 (mg/sec cm2)(cm)/ (mg/mL) as pH increased from 3 to 7. At pH 3 the undissociated acid was 97.5% and at pH 7 it was 0.4%.

RICO‐PEÑA, DELMY C., and J. ANTONIO TORRES. “Sorbic Acid and Potassium Sorbate Permeability of an Edible Methylcellulose‐Palmitic Acid Film: Water Activity and pH Effects.” Journal of Food Science 56.2 (1991): 497-499. DOI: 10.1111/j.1365-2621.1991.tb05312.x

Effect of lipid-containing, positively charged nanoemulsions on skin hydration, elasticity and erythema—An in vivo study


Dry skin and other skin disorders such as atopic dermatitis are characterized by impaired stratum corneum (SC) barrier function and by an increase in transepidermal water loss (TEWL) leading to a decrease in skin hydration. The possibility that dermatological and cosmetic products containing SC lipids could play a part in the restoration of disturbed skin barrier function is of great interest in the field of dermatology and cosmetics. The aim of the present study was to evaluate the effect of positively charged oil/water nanoemulsions (PN) containing ceramide 3B and naturally found SC lipids (PNSC) such as ceramide 3, cholesterol, and palmitic acid on skin hydration, elasticity, and erythema. Creams of PNSC were compared to PN creams, to creams with negatively charged o/w nanoemulsion and SC lipids (NNSC) and to Physiogel® cream, a SC lipid containing formulation, which is already on the market. The formulations (PN, PNSC, and NNSC) were prepared by high-pressure homogenization. After adding Carbopol 940 as thickener, particle size and stability of the creams were not significantly changed compared to the nanoemulsions. The studies were carried out on three groups, each with 14 healthy female test subjects between 25 and 50 years of age, using Corneometer® 825, Cutometer® SEM 575 and Mexameter® 18 for measurements of skin hydration, elasticity, and erythema of the skin, respectively. The creams were applied regularly and well tolerated throughout the study. All formulations increased skin hydration and elasticity. There was no significant difference between PNSC and Physiogel®. However, PNSC was significantly more effective in increasing skin hydration and elasticity than PN and NNSC indicating that phytosphingosine inducing the positive charge, SC lipids and ceramide 3B are crucial for the enhanced effect on skin hydration and viscoelasticity.

Yilmaz, Erol, and Hans-Hubert Borchert. “Effect of lipid-containing, positively charged nanoemulsions on skin hydration, elasticity and erythema—an in vivo study.” International journal of pharmaceutics 307.2 (2006): 232-238. doi:10.1016/j.ijpharm.2005.10.002

Control of Two Major Pathogens on Fresh Poultry Using a Combination Potassum Sorbate/Karbon Dioxide Packaging Treatment


Salmonella enteriditis and Staphylococcus aureus were separately inoculated onto fresh chicken thighs prior to dipping in 0, 1.0, 2.5, or 5.0% potassium sorbate solutions adjusted to pH 6.0. Treated samples were packaged in Nylon/Plexar/Surlyn bags under air, vacuum, 20%, 60%, or 100% CO2 atmospheres and stored at 10°C ± 1.0°C for 10 days. Changes in gaseous headspace composition, sorbate concentrations, surface pH, and microbial numbers were monitored during the storage period. S. enteriditis was more sensitive to potassium sorbate than S. aureus; growth on poultry of the latter organism was more effectively inhibited by exposure to high levels of CO2. Increased concentrations of sorbate dip solutions in combination with higher concentrations of CO2 in the package environment provided a more effective inhibitory system against growth of both pathogens on fresh poultry.

Gray, R. J. H., P. H. Elliott, and R. I. Tomlins. “Control of Two Major Pathogens on Fresh Poultry Using a Combination Potassum Sorbate/Karbon Dioxide Packaging Treatment.” Journal of Food science 49.1 (1984): 142-145. DOI: 10.1111/j.1365-2621.1984.tb13691.x

Sodium Hyaluronate

Studies on gelatin-containing artificial skin: II. Preparation and characterization of cross-linked gelatin-hyaluronate sponge


This study was conducted to develop a new sponge type of biomaterial to be used for either wound dressing or scaffold for tissue engineering. We were able to prepare an insoluble matrix composed of gelatin and sodium hyaluronate (HA) by dipping the soluble sponge into 90% (w/v) acetone/water mixture containing a small amount of cross-linking agent, 1-ethyl-3-3-dimethylaminoproplycarbodiimide hydrochloride, EDC. To characterize the sponge, Fourier-transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and Instron analysis were performed. The obtained results indicate that the chemically cross-linked sponge shows a cross-linking degree of 10–35%, a mean pore size of 40–160 μm, porosity of 35–67%, and a tensile strength of 10–30 gf/cm2. Especially, the porosity measured by image analysis showed a tendency to increase with HA content, resulting in an increased water uptake. The resistance to collagenase degradation in vitro increased for up to 2 days. Silver sulfadiazine (AgSD)-impregnated gelatin-HA sponge was also prepared and compared with conventional vaseline gauze by applying it onto a dorsal skin defect of wistar rat for 5, 12, and 21days. Histological results showed an enhancement of wound healing in AgSD-impregnated gelatin-HA sponge. © 1999 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 48: 631–639, 1999

Choi, Young Seon, et al. “Studies on gelatin‐containing artificial skin: II. Preparation and characterization of cross‐linked gelatin‐hyaluronate sponge.” Journal of biomedical materials research 48.5 (1999): 631-639. DOI: 10.1002/(SICI)1097-4636(1999)48:5<631::AID-JBM6>3.0.CO;2-Y;2-Y/abstract

Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal epithelial cells in vitro


Purpose: Sodium hyaluronate (hyaluronic acid) is known to promote corneal epithelial wound healing in vivo and in vitro, in animal experiments. Sodium hyaluronate is the ligand for CD44, a cell surface adhesion molecule which has been found on normal human corneal epithelial cells. The purpose of this study was to investigate the effect of sodium hyaluronate on human corneal epithelial cell migration, proliferation, and CD44 receptor expression.

Methods: Human corneal epithelial cell cultures were established from 32 donor corneoscleral rims and maintained separately in three different culture conditions: (1) culture medium only, (2) sodium hyaluronate enriched (0.6 mg/ml) medium, and (3) hydroxypropylmethylcellulose enriched (2.5 mg/ml) medium. The total area of migrating epithelial cell sheets in each case was measured by planimetry on days 4, 8, 12, and 16. Cytospin preparations of cells cultured in the different culture conditions were examined immunohistochemically for proliferation and CD44 receptor expression using antibodies directed against Ki67 and CD44 respectively.

Results: Cells cultured in the presence of sodium hyaluronate showed significantly increased migration at days 12 and 16 (Friedmen test: p = 0.0012, day 16; p = <0.001, day 12) compared with cells cultured in the other media. There was no difference in cell proliferation (Ki67) or CD44 expression on cells cultured in the different culture conditions.

Conclusions: Sodium hyaluronate promotes migration but not proliferation or CD44 expression on human corneal epithelial cells in vitro. The beneficial effect of sodium hyaluronate in corneal wound healing is likely to be related to rapid migration of cells leading to rapid wound closure. This may be facilitated by the adhesion between CD44 on the cells and hyaluronic acid, which coats the surface of the denuded cornea.

Gomes, J. A. P., et al. “Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal epithelial cells in vitro.” British journal of ophthalmology 88.6 (2004): 821-825. doi:10.1136/bjo.2003.027573

Neoagarobiose as a Novel Moisturizer with Whitening Effect


Neoagarobiose, a disaccharide, showed a higher hygroscopic ability than glycerol or hyaluronic acid, typical moisturizing reagents. Beside, neoagarobiose whitened B16 murine melanoma cells, and showed low cytotoxicity. Therefore neoagarobiose was a rare reagent showing both moisturizing and whitening effects.

Kobayashi, Reijiro, et al. “Neoagarobiose as a novel moisturizer with whitening effect.” Bioscience, biotechnology, and biochemistry 61.1 (1997): 162-163. DOI:10.1271/bbb.61.162

Studies on gelatin-based sponges. Part III: A comparative study of cross-linked gelatin/alginate, gelatin/hyaluronate and chitosan/hyaluronate sponges and their application as a wound dressing in full-thickness skin defect of rat


Novel cross-linked sponges composed of gelatin/alginate and gelatin/hyaluronate and chitosan/hyaluronate (GH, GA and CH, respectively) were prepared and compared. Six different sponges with or without silver sulfadiazine (AgSD) were applied on the full-thickness dorsal skin defect of Wistar rat. The histology and epidermal wound healing rates of the skin defects were investigated by light microscopy and computerized morphometry 5 and 12 days post-operatively. In our full-thickness wound model (diameter 1 cm), the AgSD-impregnated sponges showed good wound healing performances on the whole. However, there appeared meaningful differences of wound healing between the gelatin-based sponges (GH, GA) and the CH. GH with AgSD was found to show the best wound healing properties as a wound dressing resulting from histological findings and computerized morphometric analysis of epidermal healing.

Choi, Young Seon, et al. “Studies on gelatin-based sponges. Part III: a comparative study of cross-linked gelatin/alginate, gelatin/hyaluronate and chitosan/hyaluronate sponges and their application as a wound dressing in full-thickness skin defect of rat.” Journal of Materials Science: Materials in Medicine 12.1 (2001): 67-73. DOI


Effects of High-Molecular-Weight Sodium Hyaluronate on Experimental Osteoarthrosis Induced by the Resection of Rabbit Anterior Cruciate Ligament.


Sodium hyaluronate (HA) with a molecular weight of 202 x 104 (HA-202) was administered into the right knees of mature rabbits for the treatment of experimental osteoarthrosis induced by resection of the anterior cruciate ligament. At six and 12 weeks after the initiation of administration, the test group was compared with a group administered physiological saline solution to determine the effects on articular cartilage and synovial tissue. In both the six- and the 12-week period, cartilage degeneration proceeded with the lapse of time in both groups; however at 12 weeks, the efficacy of HA-202 in inhibiting degeneration was clearly observed at the lateral condyle of the femur and tibia where relatively marked degeneration was observed in the saline group. A comparison was also made among three groups administered HA-95 (sodium hyaluronate with a molecular weight of 95 x 104), HA-202, and saline, respectively, for 12 weeks. The saline group showed the greatest cartilage degeneration accompanied by complete disorganization of the cartilage layer and the disappearance of chondrocytes. The degeneration was less in the HA groups, and it was more significantly inhibited in the HA-202 group than in the HA-95 group.

Yoshimi, Tomohisa, et al. “Effects of high-molecular-weight sodium hyaluronate on experimental osteoarthrosis induced by the resection of rabbit anterior cruciate ligament.” Clinical orthopaedics and related research 298 (1994): 296-304.

Prevention of adhesion formation with use of sodium hyaluronate–based bioresorbable membrane in a rat model of ventral hernia repair with polypropylene mesh—A randomized, controlled study


Background: There is a high incidence of adhesions after ventral hernia repair with polypropylene mesh. Hyaluronic acid (HA)–based membrane has been shown to reduce the incidence of adhesions in the absence of prosthetic mesh. The purpose of this study was to determine the effect of HA membrane on the quantity and grade of adhesions and its effect on strength of repair after abdominal wall repair with polypropylene mesh. Methods: In 61 rats a full-thickness abdominal wall defect (excluding skin) was created, and a section of small bowel was abraded. The animals were randomized, receiving either HA membrane to cover the viscera or no membrane. The fascial defect was repaired with polypropylene mesh. Equal numbers of animals from each group were killed at 4 weeks and 8 weeks after surgery. Adhesion severity and percentage of mesh surface covered with adhesions were estimated. Tensile strength between mesh and muscle from each animal was measured. Sections of the mesh-muscle interface were examined histologically and measured for thickness and graded for inflammation and fibrosis. Results: Fifty-five animals survived until the end point. Animals in the HA membrane group had a significant reduction in (1) grade of adhesions between small bowel and mesh at 4 weeks (P = .009) and 8 weeks (P = .000001), (2) grade of adhesions between colon and mesh at 8 weeks (P = .00003), and (3) percentage of mesh covered with adhesions at 4 weeks (P = .01) and 8 weeks (P = .0000002). There was no difference between the 2 groups in tensile strength of the repairs, tissue thickness, degree of inflammation, or degree of fibrosis. Conclusions: HA membrane reduces the quantity and grade of adhesions of both small and large bowel, to polypropylene mesh in a rat model of ventral hernia repair, without compromising strength of the repair. (Surgery High molecular weight sodium hyaluronate1999;125:211-6.)

Hooker, Glen D., Brian M. Taylor, and David K. Driman. “Prevention of adhesion formation with use of sodium hyaluronate–based bioresorbable membrane in a rat model of ventral hernia repair with polypropylene mesh—A randomized, controlled study.” Surgery 125.2 (1999): 211-216. doi:10.1016/S0039-6060(99)70267-9

Clinical trial of intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee


A multi-centre randomized, double-blind, parallel-group clinical trial was carried out in 63 patients with osteoarthritis of the knee to compare the efficacy and tolerability of a course of intra-articular injections of 20 mg sodium hyaluronate with a similar course of injections of placebo. Treatment consisted of up to 11 injections over a 23-week period. Evaluation was by means of subjective symptom and activity assessments, serially during the course of treatment and also 25 weeks thereafter. Ten patients (5 of 30 on active treatment; 5 of 33 on placebo) were withdrawn prematurely. Pain on movement, assessed by visual analogue scale (VAS) showed statistically significant (p<0.05 to p<0.0001) reductions in mean scores throughout the first 11 weeks of treatment with sodium hyaluronate but smaller, non-significant, reductions with placebo treatment. The difference between treatments was significant (p<0.05) at 5 weeks. Pain at rest, also assessed by VAS, showed little change in mean scores with placebo but with sodium hyaluronate there was a progressive reduction which was significant (p<0.01) throughout the period from 5 to 23 weeks. The difference between sodium hyaluronate and placebo was significant (p<0.05 to p<0.002) at Weeks 5, 11, 15, 19 and 23. ‘Activities of daily living’ were assessed using a standard scale. There were small improvements with both treatments, significant at some assessments and somewhat greater with sodium hyaluronate than placebo, but there were no statistically significant differences between the groups. One patient developed a haemarthrosis after sodium hyaluronate injection, which may have been treatment related. Increase in knee effusion volume and the development of phlebitis in 2 other patients were of uncertain relationship to sodium hyaluronate therapy. There were no other reports of local or systemic adverse reactions to sodium hyaluronate therapy and laboratory screening investigations revealed no evidence of toxicity. These results indicate that a course of intra-articular injections of sodium hyaluronate (20 mg) is generally well tolerated in patients with osteoarthritis of the knee and that it results in significant reductions in knee pain in such patients. Further studies should be undertaken to clarify the part that sodium hyaluronate has to play in the management of patients with osteoarthritis of major joints.

Dixon, A. St J., et al. “Clinical trial of intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee.” Current medical research and opinion 11.4 (1988): 205-213. DOI:10.1185/03007998809114237

High molecular weight sodium hyaluronate


A novel mutant microorganism Streptococcus zooepidemicus HA-116 ATCC 39920, has been produced. The microorganism produces large amounts of high molecular weight hyaluronic acid. The invention provides a method of obtaining such microorganisms.

The invention also concerns a method of obtaining sodium hyaluronate which comprises growing with vigorous agitation a microorganism of the genus Streptococcus under appropriate conditions in a suitable nutrient medium containing a sugar component as a carbon source. The sugar component is present in a substantially constant concentration between 0.2 and 10 grams per liter. The medium has a substantially constant pH between about 6.0 and 7.5 and includes a substantially constant magnesium ion concentration above 0.05 grams per liter. The sodium hyaluronate excreted into the medium by the organism is purified using methods involving precipitation, redissolving and reprecipitating the hyaluronate. Composition of sodium hyaluronate which are characterized by an absence of pyrogenicity and skin irritation are obtained.

Nimrod, Abraham, et al. “High molecular weight sodium hyaluronate.” U.S. Patent No. 4,784,990. 15 Nov. 1988.

Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs


Hyaluronic acid (HA) and recombinant human insulin were co-spray dried to form a dry powder suitable for inhalation (Mass Median Aerodynamic Diameter, MMAD=1 to 4 μm). Insulin systemic levels and corresponding glucose levels were monitored following administration of the microparticles to the lungs of male Beagle dogs. Release kinetics were modified by addition of excess zinc ions (Zn2+) or hydroxypropyl cellulose (HPC). HA formulations containing insulin (10%w/w) were found to extend the mean residence time (MRT) and terminal half-life (Full-size image (<1 K)) when compared to spray dried pure insulin. Addition of Zn2+ also improved MRT (>9 fold), AUC/dose (2.5 fold) and Tmax (by a factor of 3) when compared to spray dried pure insulin. Addition of HPC improved MRT (>7 fold), AUC/dose (5 fold) and Tmax (by a factor of 3) when compared to spray dried pure insulin. Our results demonstrate the potential of HA-based dry powder drug delivery systems in the pulmonary controlled release of insulin.

Surendrakumar, K., et al. “Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs.” Journal of Controlled Release 91.3 (2003): 385-394. doi:10.1016/S0168-3659(03)00263-3

Non-Immunogenicity of a Purified Sodium Hyaluronate Preparation in Man


The immunogenicity of a sodium hyaluronate preparation for clinical use (Healon, Healonid, Pharmacia AB, Sweden) in ophthalmology and certain joint diseases has been tested in man. For immunization, two subcutaneous injections of 10 mg of sodium hyaluronate were given at an interval of 1 week. The following criteria were used as indicators of immunogenicity: skin prick test, microprecipitation test and complement analyses. No evidence for immunogenic properties was obtained in any of these tests. This refers to sodium hyaluronate itself and to the trace amounts of protein components contained in the preparation.

Richter, A. W., E. M. Ryde, and E. O. Zetterström. “Non-immunogenicity of a purified sodium hyaluronate preparation in man.” International Archives of Allergy and Immunology 59.1 (1979): 45-48. DOI:10.1159/000232238


Imidazolidinyl Urea

Gel compositions


There is provided a clear antiperspirant/deodorant gel composition. The composition is a water-in-oil emulsion having a viscosity about 7,000 cps to about 25,000 cps and a clarity from about 30 NTU or less. The composition further has an antiperspirant active, water, silicone gelling agent, and one or more silicone oils.

Carmody, Walter J. “Clear antiperspirant or deodorant; water in oil emulsion including silicone gelling agent and silicone oils; soft, nonirratating feel to skin; using such as diazolidinyl or imidazolidinyl urea as formaldehyde donor.” U.S. Patent No. 6,468,512. 22 Oct. 2002.

Methylchloroisothiazolinone/Methylisothiazolinone (Kathon CG) Biocide: Second United States Multicenter Study of Human Skin Sensitization.


Background: This is the second United States multicenter study of human skin sensitization to methylchloroisothiazolinone/methylisothiazolinone (MCI/MI). From January 1991 through March 1992 patients treated in 11 patch test clinics were patch tested to 100 ppm MCI/MI, formaldehyde 1% aqueous, quaternium-15 2% petrolatum, imidazolidinyl urea 2% petrolatum, and paraben mix 12% petrolatum.

Results: Twenty-three of the 1,259 patch test patients (1.8%) had positive patch test reactions to MCI/MI. Thirteen of the 23 (56.5%) were thought to be relevant to the presenting dermatitis. The frequency of positive patch test reactions to the other allergens was quaternium-15, 7.2%; formaldehyde, 7.1%; imidazolidinyl urea, 2.2%; and paraben mix, 1.4%.

Conclusion: Skin sensitization to MCI/MI has not changed significantly since the first United States multicenter study in 1988 to 1989. The rate of positive patch test responses to MCI/MI was comparable with that for parabens and imidazolidinyl urea and significantly less than for formaldehyde and quaternium-15.

Marks Jr, James G., et al. “Methylchloroisothiazolinone/Methylisothiazolinone (Kathon CG) Biocide: Second United States Multicenter Study of Human Skin Sensitization.” Dermatitis 4.2 (1993): 87-89.

Dermatological composition


Dermatological compositions described herein using from about 21 to about 40 wt-% urea with skin protectants of an oleaginous nature for treating a variety of dermatological conditions manifested by dry skin. The composition does not require use of traditional preservatives.

Valdez, Vitalia, and Albert Fleischner. “21 to about 40 wt-% urea with skin protectants of an oleaginous nature for treating a variety of dermatological conditions manifested by dry skin. the composition does not require use of traditional preservatives.” U.S. Patent No. 5,919,470. 6 Jul. 1999.

Contact sensitivity to preservatives in the UK, 2004–2005: results of multicentre study


Preservative sensitivity in the UK was last assessed in 2000. Given the changes in preservative usage, we have re-evaluated our patch test data in order to detect any changes in the trend of sensitization. The results of patch testing using the extended British Contact Dermatitis Society Standard series were collected from 9 dermatology centres in the UK. Positive reactions to each of 10 preservative allergens were captured together with the MOAHFLA indices for each centre. In total, 6958 patients were tested during the period 2004–2005. The current data were compared with previously published data. Formaldehyde and methylchloroisothiazolinone/methyl-isothiazolinone have the highest positivity rates at 2.0% and chloroxylenol the lowest at 0.2%. Parabens mix has the highest irritancy rate. Compared with the UK data in 2000, the positivity rate of imidazolidinyl urea (0.02 < P < 0.05) has significantly increased and that of methyldibromo glutaronitrile has significantly reduced (P < 0.001).

Jong, Cherng T., et al. “Contact sensitivity to preservatives in the UK, 2004–2005: results of multicentre study.” Contact Dermatitis 57.3 (2007): 165-168. DOI: 10.1111/j.1600-0536.2007.01181.x

Skin cell renewal regime


A novel cell renewal cosmetic regime is disclosed, which increases epidermal cell turnover without skin irritation. The regime consists of the use of four components: a cleanser, a cream, a lotion, and a tonic.

Cella, John A., et al. “Skin cell renewal regime.” U.S. Patent No. 4,272,544. 9 Jun. 1981.

Patch testing with preservatives at St John’s from 1982 to 1993


We have reviewed our patch test results for preservative allergy from 1982 to W3. 8 preservatives were included: formaldehyde. 2-bromo-2-nitropropane-1,3-diol (Bronopol™), quatenium-15 (Dowicil 200™). Imidazolidinyl urea (Germall 115™). diazolidinyl urea (Germall 11™) and 1,2-dibromo-2,4-dicyanpbutane (one of the constituents of Euxyl K 400™). Whereas the allergy rate to formaldehyde is quite stable, there is a slight increase in the imidazolidinyl urea allergy rate to formaldehyde is quite stable, there is a slight increase in the imidazolidinyl urea allergy rate. Quaternium-15’s rate a rapid rise seems to have stabilized. Although very important constituents of cosmetics, preservatives not only induce allergies on the face but also on the hands, and, as expected, the allergy rate in men and women generally differs. Among the 5 formaldehyde-releasers, there are some favoured simultaneous reactions quaternium -15 and formaldehyde, and diazolidinyl urea or imidazolidinyl urea. Coccomitant reactions between 1-brome-2-nitropropane-1,3-diol and formaldehyde are not common, and those between 2-brome-2-nitropropane-1,3-diol and disazolidynl urea or imidazolidinyl urea very uncommon. Concomitant reactions between imidazolidinyl urea, diazolidinyl urea, and formaldehyde are not very common. This supports the hypothesis that allergic reactions to the Germalls are directed toward the initial molecule rather than to formaldehyde.

Jacobs, M‐C., et al. “Patch testing with preservatives at St John’s from 1982 to 1993.” Contact dermatitis 33.4 (1995): 247-254. DOI: 10.1111/j.1600-0536.1995.tb00476.x

Formaldehyde-releasers in cosmetics in the USA and in Europe


Background: Frequencies of sensitization to formaldehyde among US patients patch tested for suspected contact dermatitis are higher than in Europe. Cosmetics are an important source of contact with formaldehyde.

Objectives: To acquire data on the frequency of use of formaldehyde-releasers in cosmetics sold in the USA and Europe and their use concentrations. To assess whether any observed differences may contribute to the discrepancies in sensitization rates.

Methods: Enquiries with Food and Drug Administration (FDA), the European Cosmetics Association, and the Dutch Cosmetics Association. Reading the labels of skin care cosmetics in a local drugstore.

Results: The FDA provided data on the presence of formaldehyde and releasers. Nearly one fifth of all cosmetics contain a releaser. In 25% of 496 examined skin care products, releasers were present. In comparable FDA data categories, the percentage was 24. No data were found on use concentrations of the releasers in cosmetics in either the USA or Europe.

Conclusions: The percentages of stay-on skin care products containing a formaldehyde-releaser are virtually identical in the USA (FDA data) and our local drugstore sample. However, this does not necessarily imply that cosmetics play no part in the differences in formaldehyde sensitization rates.

De Groot, Anton C., and Margo Veenstra. “Formaldehyde‐releasers in cosmetics in the USA and in Europe.” Contact Dermatitis 62.4 (2010): 221-224. DOI: 10.1111/j.1600-0536.2009.01623.x

A method for quantification of formaldehyde in the presence of formaldehyde donors in skin-care products


Reliable and uncomplicated methods for detection of free formaldehyde in products preserved with formaldehyde donors are desirable to decrease the risk of allergic contact dermatitis. The aim of this study was to develop a method that could be used in clinics and workplaces for quantification of free formaldehyde in products preserved with formaldehyde donors. The method developed is named the closed container diffusion (CCD) method. Formaldehyde in a sample is allowed to evaporate in a closed container and react with 2,4-dinitrophenylhydrazine coated on a glass fibre filter. The hydrazone formed is analyzed with HPLC. The method was tested on 3 different formaldehyde donors, imidazolidinyl urea, diazolidinyl urea and 2-bromo-2-nitropropane-1,3-diol, using 4 different cream bases. The results obtained with this method accord with those obtained with the official method within the European Union (EU). The method is sensitive enough for analysis of patients’ products and for control of labelled amounts of formaldehyde in technical products without solvent extraction. As a result of our studies, we observed a risk of exceeding the labelling limit for free formaldehyde in cosmetic products when using the highest amount of diazolidinyl urea allowed within the EU.

Karlberg, Ann‐Therese, et al. “A method for quantification of formaldehyde in the presence of formaldehyde donors in skin‐care products.” Contact dermatitis 38.1 (1998): 20-28. DOI: 10.1111/j.1600-0536.1998.tb05632.x

Analytical control of preservative labelling on skin creams


Contents of 23 preservatives (22 permitted and 1 non-permitted) were analysed in 67 skin creams to verify whether these products complied with the Cosmetic Directive with respect to ingredient labelling, as well as with respect to maximum allowed concentrations of the respective preservatives. The preservatives selected for the analysis were: parabens, 2-phenoxyethanol, benzoic acid, 4-hydroxybenzoic acid, sorbic acid, salicylic acid, formaldehyde and formaldehyde releasers, 3:1 mixture of 5-chloro-2-methyl-4-isothiazolin-2-one and 2-methyl-4-isothiazolin-2-one (Kathon CG), 2-bromo-2-nitropropane-1,3-diol (Bronopol), 5-bromo-2-nitro-1,3-dioxane (Bronidox) and methyldibromo glutaronitrile. 1 or more parabens were present in 87% (n=58) of the investigated products, 2-phenoxy ethanol in 49% (n=33) of the products, and formaldehyde/formaldehyde releasers were present in 51% (n=34) of the products. Kathon CG was found in 3 products, acid preservatives (except salicylic acid) in 8 products, Bronopol in 5 products, and methyldibromo glutaronitrile was present in 4 products. The contents of all of the target preservatives in the skin creams were within the maximum allowed concentrations of the respective substances. Incorrect ingredient labelling with respect to paraben content was found in 10% (n=7) of the investigated products, 33% (n=22) of the products were not declared for the content of formaldehyde/formaldehyde releaser, and 7% (n=5) products were incorrectly labelled for the content of 2-phenoxyethanol. In 1 of the products containing Kathon CG, the ratio of 5-chloro-2-methyl-4-isothiazolin-2-one to 2-methyl-4-isothiazolin-2-one (1.4:1) was not correct. 4 of the 8 products containing acid preservatives were not labelled for the content of these substances. All in all, in 45% (n=30) of the investigated skin creams ingredient labelling was incorrect with respect to preservative contents. The proportion of incorrect labelling is reduced to 23% (n=15), when the formaldehyde content in skin creams below 30 ppm is not accounted.

Rastogi, Suresh Chandra. “Analytical control of preservative labelling on skin creams.” Contact Dermatitis 43.6 (2000): 339-343. DOI: 10.1034/j.1600-0536.2000.043006339.x

Antiinflammatory skin moisturizing composition and method of preparing same


A long lasting, esthetically pleasing medicated skin care moisturizing composition comprising

(1) an oil phase comprising oil from about 30% to about 80% and a non-ionic surface active agent having an HLB number of about 7 to about 12, wherein the non-ionic surface active agent is present in an amount of about 5% to about 9%;

(2) an aqueous phase comprising an aqueous thickening agent from about 0.05% to about 5% and water from about 15% to about 65%;

(3) an effective amount of a topical medicament; wherein the medicament is a corticosteroid and the oil phase is added to the aqueous phase to form an emulsion and a topical medicament admixed into the emulsion has been developed.

The method of preparation of the composition and a method of treating skin with the composition are also disclosed.

Geria, Navin M. “Antiinflammatory skin moisturizing composition and method of preparing same.” U.S. Patent No. 4,992,478. 12 Feb. 1991.

Sensitive-skin care regime


A method of decreasing the sensitivity of the skin without causing irritation is described, using a four component cosmetic regime. The four components comprising the regime are: a cleanser, a toner, a moisturizer, and a cream.

Flom, Merlyn G., et al. “Sensitive-skin care regime.” U.S. Patent No. 4,368,187. 11 Jan. 1983.

Algae Extract

Algae Extract-Mediated Stimulation and Protection of Proteasome Activity Within Human Keratinocytes Exposed to UVA and UVB Irradiation


Sun exposure is the major environmental influence for epidermal cells; the harmful effect of UV radiation on skin is related to the generation of reactive oxygen species that alter cellular components including proteins. It is now well established that the proteasome is responsible for the degradation of most of oxidized proteins and that impairment of proteasome function is a hallmark of cellular aging. In a previous study, we investigated the effects of UV irradiation on proteasomes in human keratinocyte cultures and showed that all three peptidase activities were decreased 24 h after irradiation of the cells. Increased levels of oxidatively modified proteins were observed in irradiated cells and were found to act as endogenous inhibitors of the proteasome. We report here on the stimulating and protective effects of an algae extract, prepared from Phaeodactylum tricornutum, on proteasome peptidase activities of human keratinocytes exposed to UVA and UVB irradiation. In addition, preserving proteasome function resulted in lowering the extent of the irradiation-induced protein oxidative damage, opening up new strategies for protection of epidermal cells against the detrimental effects of UV irradiation.

Bulteau, Anne-Laure, et al. “Algae extract-mediated stimulation and protection of proteasome activity within human keratinocytes exposed to UVA and UVB irradiation.” Antioxidants & redox signaling 8.1-2 (2006): 136-143. doi:10.1089/ars.2006.8.136.

Algae Extract Protection Effect on Oxidized Protein Level in Human Stratum Corneum


Modification of proteins by reactive oxygen species is implicated in different disorders. The proteasome is a multicatalytic proteinase in charge of intracellular protein turnover and of oxidized proteins degradation. Consequently, proteasome function is very important in controlling the level of altered proteins in eukaryotic cells. Evidence for a decline in proteasome activity during skin photo-aging has been provided in Bulteau et al. in 2002. The ability of a lipid algae extract (Phaeodactylum tricornutum) to stimulate 20S proteasome peptidase activities was described by Nizard et al. in 2001. Furthermore, keratinocytes treated with Phaeodactylum tricornutum extract and then UVA and UVB irradiated, exhibited a sustained level of proteasome activitiy comparable to the one of nonirradiated cells. The level of modified proteins can be quantified by measurement of protein carbonyl content (Oxyblot technique), which has been shown to increase with aging and other disorders. In this paper, it is described that, in the presence of this lipid algae extract, the level of oxidized proteins is reduced, as assessed by the Oxyblot technique. These results are obtained both with culture of human keratinocytes and stratum corneum skin cells (obtained by stripping) from human volunteers. Altogether, these results argue for the presence of compounds in this algae extract that have a stimulating and/or protective effect on proteasome activity, resulting in a decreased level of protein oxidation.

NIZARD, CARINE, et al. “Algae extract protection effect on oxidized protein level in human stratum corneum.” Annals of the New York Academy of Sciences 1019.1 (2004): 219-222. DOI: 10.1196/annals.1297.036

Symptoms of hay fever caused by algae


  1. A potent antigen was prepared from algae growing in a lake in Waukesha County, Wis.
  2. This antigen elicited positive skin tests in an individual whose symptoms of hay fever were aggravated by swimming in that lake and in an individual who did not have pollinosis, but who likewise developed symptoms of hay fever.
  3. Positive passive transfer tests to algae extract were obtained from one of the two patients.
  4. The antigen was effective in the treatment of this allergic condition.
  5. A specimen of algae preserved in formaldehyde retained a high titer of antigenicity for two and one-half years.

Heise, Herman A. “Symptoms of hay fever caused by algae.” Journal of Allergy 20.5 (1949): 383-385. doi:10.1016/0021-8707(49)90029-5

Functional, antioxidant and film-forming properties of tuna-skin gelatin with a brown algae extract


Characteristics and functional properties of gelatin from skin of Atlantic Bluefin tuna (Thunnus thynnus) were investigated. The gelatin was extracted by an acid-swelling process in the presence of different concentrations of commercial pepsin, followed by subsequent heating. The extraction yield was higher when increasing concentrations of pepsin were used during the swelling process. Emulsion activity index, foam formation ability and foam stability of gelatin increased with the increase of gelatin concentration. Antioxidant properties (ferric-reducing ability and DPPH-radical-scavenging capacity) of gelatin-based edible films containing aqueous or methanolic extracts of brown algae (Cystoseira barbata) were also assessed. For comparative purposes, tuna-skin gelatin edible film with BHA was studied. Antioxidant properties of the films were increased significantly when natural extracts were added.

External preparation for application to the skin containing lidocaine


An external preparation for application to the skin containing lidocaine which comprises a drug-retaining layer placed on a support, wherein said drug-retaining layer comprises an adhesive gel base and 1 to 10% by weight of lidocaine, said base comprising a water-soluble high molecular weight substance, water and a water-retaining agent, which can release the active lidocaine gradually and constantly so that lidocaine is transdermally absorbed for a long period of time.

Ono, Masahiro, et al. “External preparation for application to the skin containing lidocaine.” U.S. Patent No. 5,827,529. 27 Oct. 1998.

Respiratory allergy to algae: clinical aspects.


A comprehensive investigation was done to evaluate the allergenic algae in the Delhi area. Results of 4,000 skin tests performed on 400 patients suffering from naso-bronchial allergy and 300 skin tests on 30 healthy persons with 10 common algae isolated from the Dehli atmosphere are presented and compared. Positive skin reactions (1+ to 3+) to algae extracts ranged from 25.7% with Lyngbya major extract to 1.7% with Oscillatoria simplicissima extract; in healthy non-allergic volunteers there were no positive skin reactions. The Prausnitz-Küstner (PK), bronchial provocation and conjunctival tests were negative in patients with negative skin reactions; in patients with positive skin reactions PK was positive in 70.9%, bronchial provocation in 50% and conjunctival in 48.5%. Levels of total IgE in patients with naso-bronchial allergy were higher, ranging from 1,225 international units per ml to 1,550 international units per ml, while in healthy volunteers the values were less than 885 international units per ml.

Mittal, A., M. K. Agarwal, and D. N. Shivpuri. “Respiratory allergy to algae: clinical aspects.” Annals of allergy 42.4 (1979): 253-256.

Utilization of algae extract for the preparation of pharmaceutical, cosmetic, food or agricultural compositions


The present invention relates to the utilization of algae extracts obtained by extraction in liquid phase, or of at least one active substance isolated from such an extract or obtained by chemical synthesis, selected in particular among the fucols, polyfucols, diphloretols, polyphloretols, bifuhalols, polyfuhalols, phloretols, for the preparation of pharmaceutical, cosmetic, food or agricultural compositions with an anti-radical activity, particularly towards the superoxide radical. The algae used are brown, green or red macroscopic algae and in particular Fucus vesiculosus.

Briand, Xavier. “Antiradical activity towards superoxide radical.” U.S. Patent No. 5,508,033. 16 Apr. 1996.

Sensitivity of skin and bronchial mucosa to green algae


Six green algal strains were examined for their possible allergenicity to humans. Of 79 atopic patients tested with algal extracts, 47 gave positive skin tests. Non-atopic individuals showed no skin reactivity. Skin-sensitizing antibodies were passively transferred from 6 of 8 patients tested with Chlorella vulgaris. In the same group of patients, precipitating antibodies were not observed. Bronchial mucosal tests, evaluated by changes in the peak expiratory flow rate and by the appearance of clinical wheezing, were performed on 8 patients in whom cutaneous reactivity had been pronounced. Positive responses to acrosolized extracts of Chlorella vulgaris were obtained in 5 of these patients. These results suggest that positive skin tests to green algae are immunologically significant and that these organisms may be etiological agents in human respiratory allergies.

Bernstein, I. Leonard, and Robert S. Safferman. “Sensitivity of skin and bronchial mucosa to green algae.” Journal of Allergy 38.3 (1966): 166-173. doi:10.1016/0021-8707(66)90039-6

Sunscreen preparation


A high-SPF composition is provided which is quick drying, waterproof and anti-perspiration penetrating which after application rapidly is very dry and soft to the touch comprising a sunscreen with both UVA and UVB components, an algae extract and aloe vera, and tapioca powder. In a further example, an enhancing agent consisting of styrene acrylates copolymer is added.

Randall, William B., and Cary L. Prida. “Consists of ultraviolet radiation protecting agent benzophenone-3 and or butyl methoxydibenzoylmethane, copolymer of styrene-acrylate as enhancer, tapioca powder, and marine algae extract.” U.S. Patent No. 5,945,090. 31 Aug. 1999.

Topical analgesic using water soluble capsaicin


A water-based topical analgesic and method of application wherein the analgesic contains capsicum, capsicum oleoresin and/or capsaicin. This analgesic is applied to the skin to provide relief for rheumatoid arthritis, osteoarthritis, and the like.

Conant, Dale. “Capsaicin, magnesium oxide, disodium edta and water; no harsh solvents, gentle to skin; treating rheumatoid arthritis, muscle pain.” U.S. Patent No. 5,910,512. 8 Jun. 1999.


Pullulan content of the ethanol precipitate from fermented agro-industrial wastes


Ethanol-precipitated substances after fermentation of various

agro-industrial wastes by Aureobasidium pullulans were examined for their pullulan content. Grape skin pulp extract, starch waste, olive oil waste effluents and molasses served as substrates for the fermentation. A glucose-based defined medium was used for comparison purposes. Samples were analysed by an enzyme-coupled assay method and by high-performance anion-exchange chromatography with pulsed amperometric detection after enzymic hydrolysis with pullulanase. Fermentation of grape skin pulp extract gave 22.3 g l−1 ethanol precipitate, which was relatively pure pullulan (97.4% w/w) as assessed by the coupled-enzyme assay. Hydrolysed starch gave only 12.9 g l−1 ethanol precipitate, which increased to 30.8 g l−1 when the medium was supplemented with NH4NO3 and K2HPO4; this again was relatively pure pullulan (88.6% w/w). Molasses and olive oil wastes produced heterogeneous ethanol-precipitated substances containing small amounts of pullulan, even when supplemented with nitrogen and phosphate. Overall, grape skin pulp should be considered as the best substrate for pullulan production. Starch waste requires several hydrolyis steps to provide a usable carbon source, which reduces its economic attraction as an industrial process.

Israilides, C. J., et al. “Pullulan content of the ethanol precipitate from fermented agro-industrial wastes.” Applied Microbiology and Biotechnology 49.5 (1998): 613-617. DOI 10.1007/s002530051222

Potential uses and applications of treated wine waste: a review


Recently, there has been an upsurge in the exploitation of the waste materials generated by the wine industry. Wine waste is characterised by the presence of natural antioxidants much safer than synthetic antioxidants. Wine waste-derived antioxidants have been recently used in the food industry. Moreover, wine waste can be potentially used as soil conditioner, as adsorbent for heavy metals, for fertiliser and for pullulan production. This review aims at presenting the most important and economically viable applications of treated wine waste.

Arvanitoyannis, Ioannis S., Demetrios Ladas, and Athanasios Mavromatis. “Potential uses and applications of treated wine waste: a review.” International journal of food science & technology 41.5 (2006): 475-487. DOI: 10.1111/j.1365-2621.2005.01111.x

Effects of cholesterol-bearing pullulan (CHP)-nanogels in combination with prostaglandin E1 on wound healing


The cholesterol-bearing pullulan (CHP)-nanogels are able to trap hydrophobic drugs or proteins inside the nanogels, which is potential in application to drug delivery system and tissue engineering. On the other hand, prostaglandin E1 (PGE1) plays important roles in wound healing and PGE1 ointment has been clinically used to treat chronic skin ulcers and wounds. The purpose of this study is to evaluate effects of CHP nanogels in combination with prostaglandin E1 on wound healing in full thickness skin defect model. A square skin defect (1 × 1 cm2) of full thickness was created on the dorsal of Wistar rats. The wound was treated with CHP nanogels without PGE1 (CHP group) or CHP nanogels containing with PGE1 (CHP/PGE1 group) or PGE1 ointment (PGE1 ointment group). In both CHP/PGE1 and PGE1 ointment groups, ∼6 μg of PGE1 was applied to each wound. In the control group, the wound was untreated. The wound was evaluated in measuring wound area and histologically. In CHP/PGE1 group, the rate of wound size reduction was significantly higher than the ones of other groups. Histologically, CHP/PGE1 promoted neoepithelialization, neovascularization, and wound closure compared to the other treatments. These results suggest that CHP in combination with PGE1 can promote wound healing, which confirms the efficiency of CHP nanogels-based drug delivery system. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009

DOI: 10.1002/jbm.b.31373

Pullulan Hydrogels Improve Mesenchymal Stem Cell Delivery into High-Oxidative-Stress Wounds


Thumbnail image of graphical abstract

Cell-based therapies for wound repair are limited by inefficient delivery systems that fail to protect cells from the acute inflammatory environment. Here, a biomimetic hydrogel system is described that is based on the polymer pullulan, a carbohydrate glucan known to exhibit potent antioxidant capabilities. It is shown that pullulan hydrogels are an effective cell delivery system and improve mesenchymal stem cell survival and engraftment in high-oxidative-stress environments. The results suggest that glucan hydrogel systems may prove beneficial for progenitor-cell-based approaches to skin regeneration.

Wong, Victor W., et al. “Pullulan Hydrogels Improve Mesenchymal Stem Cell Delivery into High‐Oxidative‐Stress Wounds.” Macromolecular bioscience 11.11 (2011): 1458-1466. DOI: 10.1002/mabi.201100180

Engineered Pullulan–Collagen Composite Dermal Hydrogels Improve Early Cutaneous Wound Healing


New strategies for skin regeneration are needed to address the significant medical burden caused by cutaneous wounds and disease. In this study, pullulan–collagen composite hydrogel matrices were fabricated using a salt-induced phase inversion technique, resulting in a structured yet soft scaffold for skin engineering. Salt crystallization induced interconnected pore formation, and modification of collagen concentration permitted regulation of scaffold pore size. Hydrogel architecture recapitulated the reticular distribution of human dermal matrix while maintaining flexible properties essential for skin applications. In vitro, collagen hydrogel scaffolds retained their open porous architecture and viably sustained human fibroblasts and murine mesenchymal stem cells and endothelial cells. In vivo, hydrogel-treated murine excisional wounds demonstrated improved wound closure, which was associated with increased recruitment of stromal cells and formation of vascularized granulation tissue. In conclusion, salt-induced phase inversion techniques can be used to create modifiable pullulan–collagen composite dermal scaffolds that augment early wound healing. These novel biomatrices can potentially serve as a structured delivery template for cells and biomolecules in regenerative skin applications.

Wong, Victor W., et al. “Engineered pullulan–collagen composite dermal hydrogels improve early cutaneous wound healing.” Tissue Engineering Part A 17.5-6 (2010): 631-644.

Pullulan and polyvinyl alcohol based film forming compositions


Compositions for forming a peelable, cosmetic film on the skin of a subject are provided. The compositions provided contain 3 to 30 wt % pullulan and 3 to 30 wt % polyvinyl alcohol; wherein the combination of pullulan and polyvinyl alcohol constitute 6 to 33 wt % of the composition. The invention also relates to a method of forming a peelable, cosmetic film on the skin of a subject including applying a composition to the skin of the subject, wherein the composition contains 3 to 30 wt % pullulan and 3 to 30 wt % polyvinyl alcohol; wherein the combination of pullulan and polyvinyl alcohol constitute 6 to 33 wt % of the composition.

O’Halloran, David, and Yelena Zolotarsky. “Pullulan and polyvinyl alcohol based film forming compositions.” U.S. Patent Application No. 10/256,264.

Fluorophore-assisted carbohydrate electrophoresis (FACE) of oligosaccharides: efficiency of labelling and high-resolution separation


Reductive amination is a common technique for the derivatisation of reducing carbohydrates, thereby providing appropriate chromophores or fluorophores to overcome native detection deficiencies. Rarely, however, is the issue of labelling efficiency addressed for substrates larger than monosaccharides. Utilising a variety of radiolabelled synthetic maltooligosaccharides, we now present data on the APTS labelling efficiency for substrates up to an average degree of polymerization (dp) of 135. The labelling reaction was found to be highly reproducible and independent of average chain length between dp 3 and dp 135, with an average efficiency of 80%. Glucose (95%) and maltose (88%) were labelled more efficiently. In addition to this work, electrophoretic methodologies have been developed to aid the characterization of APTS-labelled oligosaccharide distributions across a wide range of chain lengths. Fluorescent imaging of polyacrylamide slab gels provides flexibility of gel format, and conditions that can be adapted to the resolution and quantification of short oligosaccharide populations (less than dp 30) or to enable the observation of polysaccharides. A capillary gel electrophoretic method was developed using laser–induced fluorescence (LIF) detection to fully resolve and quantify maltooligosaccharides up to approximately dp 100, a technique that finds particular use in the analysis of oligosaccharide distributions obtained from isoamylase debranching of the amylopectin component of starch. A comparison of data reproducibility across a range of chain lengths established the superiority of results obtained by the capillary gel electrophoretic method over a previously reported method involving DNA sequencer-mediated electrophoretic separation.

Yamaki, Kazuhiro, et al. “External skin care composition.” U.S. Patent No. 6,878,378. 12 Apr. 2005. doi:10.1016/S0008-6215(97)10085-4

Pullulan based film forming cosmetic compositions


Compositions for forming a visible and distinctive cosmetic film on the skin of a subject are provided. The compositions provided contain 3 to 15 wt % pullulan. The invention also relates to a method of forming a visible and distinctive cosmetic film on the skin of a subject including applying a composition to the skin of the subject, wherein the composition contains 3 to 15 wt % pullulan.

O’Halloran, David, and Yelena Zolotarsky. “Pullulan based film forming cosmetic compositions.” U.S. Patent Application No. 10/256,234.

The antimicrobial activity of pullulan film incorporated with meadowsweet flower extracts (Filipendulae ulmariae flos) on postharvest quality of apples


This study examined the antimicrobial activity of pullulan films with incorporated meadowsweet flower extracts (EMFs) and the effectiveness of these coatings in the prolonging of apple stability in various storage conditions. Pullulan was obtained from a batch culture of white mutant Aureobasidium pullulans B-1. The content of phenolic components in two extracts-water–ethanol (weEMF) and ethanol one (eEMF)-was compared using the HPLC method. Compared to eEMF, a significantly higher content was noted of phenolic acids and flavonoids in weEMF and its increased activity in inhibiting microorganism growth. Pullulan films with incorporated EMFs were obtained from the solutions to which they were added in concentrations of 3, 6, 9, 12 and 15%. These films were stable and homogenous, and to a higher degree inhibited the growth of tested bacteria than fungi. Apples of the Jonagored variety were coated with a pullulan coating containing 12% EMF. The pullulan coating with EMFs evened and unified the surface of apple skins. Pullulan coating with weEMF more effectively inhibited the growth of natural mesophilic microflora, the amount of which decreased by two logarithmic cycles at the end of storage. EMF addition to the coating significantly limited the growth of the Rhizopus arrhizus mold inoculated to the apples. EMF addition to pullulan coating did not affect color changes nor did apples loss weight during their storage. Pullulan coatings with incorporated EMFs may protect apple quality during their storage and turnover in various temperatures and time conditions.

Gniewosz, Małgorzata, et al. “The antimicrobial activity of pullulan film incorporated with meadowsweet flower extracts (Filipendulae ulmariae flos) on postharvest quality of apples.” Food Control 37 (2014): 351-361. doi:10.1016/j.foodcont.2013.09.049

Isolation and Properties of a Sialoglycoprotein from the Skin Mucus of the Stingray Dasyatis akajei


A sialoglycoprotein (SGP) has been purified from the skin mucus of the stingray Dasyatis akajei. SGP contained 22.1% (w/w) NeuAc, 24.4% GalNAc, 9.9% GlcNAc, 6.1% Gal, and 27% amino acids, and its average molecular weight (Mr) was estimated to be 500, 000. SGP was very rich in Thr (32 mol%) and Ser (12 mol%). Treatment of SGP with alkali (β-elimination of carbohydrate chains) result-ed in the destruction of 70% of Thr and Ser, indicating that the carbohydrate chains were attached through these amino acids. Exhaustive digestion of SGP by actinase yielded a highly glycosylated glycopeptide with Mr of 50, 000. Based on these results, it is assumed that a SGPmolecule bears more than 400 oligosaccharide chains which are attached to the Thr and Ser residues of the polypeptide backbone and spaced at an average of 3 amino acids apart.

Sumi, Toshihisa, et al. “Isolation and Properties of a Sialoglycoprotein from the Skin Mucus of the Stingray Dasyatis akajei.” Fisheries science 63.3 (1997): 453-458.

Citric Acid

Citric Acid Increases Viable Epidermal Thickness and Glycosaminoglycan Content of Sundamaged Skin


background Recently, there has been an exponential increase in the use of alpha-hydroxy acids in dermatologic practice. Their inclusion in a myriad of cosmetic preparations underscores their popularity. Among the clinical effects of alpha-hydroxy acids are their ability to prevent the atropy resulting from potent topical corticosteroids, improve the appearance of photoaged skin, and correct disorders of keratinization. Despite this range of desirable effects, very little is known about the specific changes produced by various alpha-hydroxy acid preparations in the epidermis and dermal extracellular matrix. Previous work by others has demonstrated the ability of another alpha-hydroxy acid to increase viable epidermal thickness, and derma! glycosaminoglycans.

objective In this study, we examined the effect of 20% citric acid lotion, as compared with vehicle alone, on skin thickness. viable epidermal thickness, and dermal glycosaminoglycan constent. Biopsy samples were harvested after 3 months of treatment.

results Image analysis of biopsy sections revealed increases in viable epidermal thickness and dermal glycosaminoglycans in treated skin.

conclustions Topical citric acid produces changes similar to those observed in response to glycolic acid, ammonium lactate, and retinoic acid including increases in epidermal and dermal glycosaminoglycans and viable epidermal thickness. Further studies of citric acid and other alpha-hydroxy acids are warranted to clarify their clinical effects and mechanisms of action.

Bernstein, Eric F., et al. “Citric acid increases viable epidermal thickness and glycosaminoglycan content of sundamaged skin.” Dermatologic surgery 23.8 (1997): 689-694. DOI: 10.1111/j.1524-4725.1997.tb00391.x

Effects of α-hydroxy acids on photoaged skin: Apilot clinical, histologic, and ultrastructural study


Objective: Our purpose was to determine the effects of AHAs on photoaged human skin by clinical and microanalytic means.

Methods: Patients applied a lotion containing 25% glycolic, lactic, or citric acid to one forearmand a placebo lotion to the opposite forearm for an average of 6 months. Thickness of forearm skin was measured throughout the study. Biopsy specimens from both forearms were processed for analysis at the end of the study.

Results: Treatment with AHAs caused an approximate 25% increase in skin thickness. The epidermis was thicker and papillary dermal changes included increased thickness, increased acid mucopolysaccharides, improved quality of elastic fibers, and increased density of collagen. No inflammation was evident.

Conclusion: Treatment with AHAs produced significant reversal of epidermal and dermalmarkers of photoaging.

Ditre, Chérie M., et al. “Effects of α-hydroxy acids on photoaged skin: Apilot clinical, histologic, and ultrastructural study.” Journal of the American Academy of Dermatology 34.2 (1996): 187-195. doi:10.1016/S0190-9622(96)80110-1

Healing of periodontal connective tissues following surgical wounding and application of citric acid in dogs


Topical application of citric acid to a root surface which has been scaled and root planed results in exposure of collagen fibrils of the dentin matrix. The purpose of this study was to examine the healing of gingival connective tissue adjacent to a root planed and subsequently acid conditioned root surface and to determine whether the exposure of dentin or cementum matrix collagen would facilitate the reestablishment of an attachment between the healing connective tissue and the root surface. Full thickness flaps were raised and labial alveolar bone removed over maxillary incisor roots of seven Labrador retrievers. The exposed root surface was planed before etching with citric acid (pH 1) for 3 min. The flap was then repositioned at its original level. Block sections were obtained after 7, 14, 21 and 42 days and the interface between the root surface and the healing wound tissue studied by light and electron microscopy. Compared to conventional flap surgery in the same animals, application of citric acid to the instrumented root surface resulted in an improved rate of connective tissue healing as well as a rapid and consistent reestablishment of connective tissue attachment through extensive interdigitation of new and old collagen fibrils at the tooth-gingiva interface. Subsequent reinforcement of the established connective tissue attachment included recalcification of the acid-affected dentin and deposition of new cementum.

Ririe, Craig M., Max Crigger, and Knut A. Selvig. “Healing of periodontal connective tissues following surgical wounding and application of citric acid in dogs.” Journal of Periodontal Research 15.3 (1980): 314-327. DOI: 10.1111/j.1600-0765.1980.tb00287.x


Effects of citric acid on diseased root surfaces


The effect of topically applied citric acid on periodontally diseased root surfaces was evaluated using the scanning (SEM) and transmission (TEM) electron microscopes. Results with the SEM indicate that acid application had no effect on specimens that had not been root planed. After application to root planed surfaces, however, the acid priduced a fiber-like surface with frequent depressions. TEM observations showed that the acid application produced a four micron wide demineralized zone, which was characterized by exposed collagen fibrils. These fibrils seemed to be continuous between the mineralized and demineralized zones of the root.

It appears that the relative success of the citric acid application in periodontal reattachment procedures is realted to the fact that the acid causes exposure of collagen fibrils in the dentin matrix, thus providing a suitable nidus for splicing with new fibrils during the healing process.

Garrett, John S., Max Crigger, and Jan Egelberg. “Effects of citric acid on diseased root surfaces.” Journal of Periodontal Research 13.2 (1978): 155-163. DOI: 10.1111/j.1600-0765.1978.tb00164.x

Glycolic Acid Treatment Increases Type I Collagen mRNA and Hyaluronic Acid Content of Human Skin


Background. Chronic solar irradiation results in both morphologic and functional changes in affected skin. α-hydroxy acids, such as glycolic acid, have been shown to improve photodamaged skin.

Objective. To investigate alterations in collagen gene induction and epidermal and dermal hyaluronic acid production as a result of administered glycolic acid.

Methods. In this study we compared collagen gene expression from skin biopsy specimens, and epidermal and dermal hyaluronic acid immunohistochemical staining between glycolic acid-treated and vehicle-treated skin. Forearm skin was treated with 20% glycolic acid lotion or a lotion vehicle control twice a day for 3 months.

Results. Epidermal and dermal hyaluronic acid and collagen gene expression were all increased in glycolic acid-treated skin as compared to vehicle-treated controls.

Conclusion. Our data suggest that epidermal and dermal remodeling of the extracellular matrix results from glycolic acid treatment. Longer treatment intervals may result in collagen deposition as suggested by the measured increase in mRNA.

Bernstein, Eric F., et al. “Glycolic acid treatment increases type I collagen mRNA and hyaluronic acid content of human skin.” Dermatologic surgery 27.5 (2001): 429-433. DOI: 10.1046/j.1524-4725.2001.00234.x

Effects of alpha-hydroxy acids on the human skin of Japanese subjects: The rationale for chemical peeling


Alpha-hydroxy acid (AHA) agents, such as glycolic acid and lactic acid, have been used as therapeutic agents for more than a quarter of a century. Recently, they have been used as agents to rejuvenate photo-aged skin. It is believed that these AHA agents induce the epidermis to remodel and accelerate desquamation, thus exerting their therapeutic effects. In this study, we investigated the histological differences in skin treated with glycolic, lactic, citric and acetic acids once daily for 6 weeks. The melanin pigments in the basal layer were less prominent in the glycolic and lactic acid-treated skin than in the citric and acetic acid-treated skin. The melanin deposits in the horny layers were equal for all AHA. However, the melanin deposits in the squamous layers were less prominent in the glycolic and lactic acid-treated skins than in the citric and acetic acid-treated skins; this was analogous to observations of the basal layers. Collagen I and procollagen I were increased after treatment with glycolic, lactic and citric acid in the upper dermis, but were not increased with acetic acid treatment. However, the staining of the epidermis and dermis for matrix metalloproteinase-1 (MMP-1) after treatment was not significantly different among the agents. Our data suggest that longer treatment intervals with glycolic and lactic acid can cause improvements in both the epidermal and dermal components and support the usefulness of AHA for rejuvenating photo-damaged skin.

Yamamoto, Yuki, et al. “Effects of alpha‐hydroxy acids on the human skin of Japanese subjects: The rationale for chemical peeling.” The Journal of dermatology 33.1 (2006): 16-22. DOI: 10.1111/j.1346-8138.2006.00003.x

Treatment of skin keratoses with α-hydroxy acids and related compounds


Preventive as well as therapeutic treatment to alleviate the symptoms of skin keratoses consisting of topical application of a solution, gel, lotion, cream or ointment containing one or more of the α- or β-hydroxy acids or α-keto acids, esters thereof, and their amine salts is disclosed. The compounds include free acid or amine salt forms of α-hydroxy-butyric acid, α-hydroxyisobutyric acid, α-hydroxyisocaproic acid, α-hydroxyisovaleric, atrolactic acid, β-hydroxybutyric acid, β-phenyl lactic acid, β-phenylpyruvic acid, citric acid, ethyl pyruvate, galacturonic acid, glucoheptonic acid, glucoheptono 1,4-lactone, gluconic acid, gluconolactone, glucuronic acid, glucuronolactone, glycolic acid, isopropyl pyruvate, lactic acid, malic acid, mandelic acid, methyl pyruvate, mucic acid, pyruvic acid, saccharic acid, saccharic acid 1,4-lactone, tartaric acid, and tartronic acid. The therapeutic composition may include one or more of the compounds present in the total amount of from three to thirty percent. Topical application to affected areas has been found to achieve from substantial to complete remissions of the keratoses in humans.

Van Scott, Eugene J., and J. Yu Ruey. “Treatment of skin keratoses with α-hydroxy acids and related compounds.” U.S. Patent No. 4,234,599. 18 Nov. 1980.

The influence of different acids and pepsin on the extractability of collagen from the skin of Baltic cod (Gadus morhua)


Solutions of (0.5 M) citric, lactic and acetic acids and 0.15 M HCl were used for the extraction of collagen from the whole skins of Baltic cod (Gadus morhua). The extractions were performed at a temperature of 4 °C for 24, 48 and 72 h using a solid/solution ratio of 1:6 (w/v). Of the acids used, HCl was the least effective solvent for collagen. The maximal yield of collagen extracted with citric acid was 60%. Collagen extraction with acetic or lactic acid give a maximal yield of about 90% with HCl yielding of only 18%. After enzymatic treatment of cod skin the yield of protein extracted with HCl and citric acids increased to 40% and 20%, respectively. Collagen was completely solubilized under the same conditions in acetic and lactic acids. Electrophoretic analysis of collagens extracted in HCl and citric acids with enzymatic treatment proved that the isolated protein was denaturated. The solutions of acetic and lactic acids are solvents for native collagen.

Skierka, Elżbieta, and Maria Sadowska. “The influence of different acids and pepsin on the extractability of collagen from the skin of Baltic cod (Gadus morhua).” Food chemistry 105.3 (2007): 1302-1306. doi:10.1016/j.foodchem.2007.04.030

A biomarker that identifies senescent human cells in culture and in aging skin in vivo


Normal somatic cells invariably enter a state of irreversibly arrested growth and altered function after a finite number of divisions. This process, termed replicative senescence, is thought to be a tumor-suppressive mechanism and an underlying cause of aging. There is ample evidence that escape from senescence, or immortality, is important for malignant transformation. By contrast, the role of replicative senescence in organismic aging is controversial. Studies on cells cultured from donors of different ages, genetic backgrounds, or species suggest that senescence occurs in vivo and that organismic lifespan and cell replicative lifespan are under common genetic control. However, senescent cells cannot be distinguished from quiescent or terminally differentiated cells in tissues. Thus, evidence that senescent cells exist and accumulate with age in vivo is lacking. We show that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture. This marker was expressed by senescent, but not presenescent, fibroblasts and keratinocytes but was absent from quiescent fibroblasts and terminally differentiated keratinocytes. It was also absent from immortal cells but was induced by genetic manipulations that reversed immortality. In skin samples from human donors of different age, there was an age-dependent increase in this marker in dermal fibroblasts and epidermal keratinocytes. This marker provides in situ evidence that senescent cells may exist and accumulate with age in vivo.

Dimri, Goberdhan P., et al. “A biomarker that identifies senescent human cells in culture and in aging skin in vivo.” Proceedings of the National Academy of Sciences 92.20 (1995): 9363-9367.


Extracting Conditions for Megrim (Lepidorhombus boscii) Skin Collagen Affect Functional Properties of the Resulting Gelatin


Various procedures for extracting collagen and/or gelatin from megrim skins were compared on the basis of gelatin functional properties. It was possible to prepare a dry powder of soluble collagen with good viscoelastic and gelling properties, which can be converted into gelatin by dissolving at temperatures above 45 °C. Physical properties of gelatins are influenced more by extracting conditions than by imino acid composition. A high-quality, readily-dissolved gelatin was obtained from megrim skins using a pretreatment of the skins with NaCl and dilute NaOH, then swelling with 0.05 M acetic acid followed by an extraction step in water at 45 °C.

Montero, P., and M. C. Gómez‐Guillén. “Extracting conditions for megrim (Lepidorhombus boscii) skin collagen affect functional properties of the resulting gelatin.” Journal of Food Science 65.3 (2000): 434-438. DOI: 10.1111/j.1365-2621.2000.tb16022.x


Chamomile (Matricaria recutita) Extract

Allergic conjunctivitis to chamomile tea.


Eye washing with chamomile tea is a folk remedy used by the general public to treat conjunctivitis and other ocular reactions. Chamomile is also found in many cosmetic products. Some cases of contact dermatitis (but not reactions of type I) were reported following its topical applications. We present seven hay fever patients that suffered from conjunctivitis; two of them also had lid angioedema after eye washing with chamomile tea. All seven patients had positive skin prick tests to the chamomile tea extract, Matricaria chamomilla pollen and Artemisia vulgaris pollen extracts. Positive conjunctival provocations were also observed in all the patients with the chamomile tea extract. In contrast, no symptoms were observed after oral challenges with this infusion. IgE activity against chamomile tea and Matricaria and Artemisia extracts (composite pollens) was detected by ELISA in the seven patients’ sera. A cross reactivity among the above extracts was observed by an ELISA inhibition study. In all cases, the IgE activity to chamomile tea could fully be absorbed by Matricaria pollen extract. Skin prick tests and conjunctival provocation tests also performed in 100 hay fever controls revealed a positive immediate skin response to Artemisia in 15 patients, eight of them also to Matricaria pollen and five of them to Chamomile tea as well. Only two of the last patients had a positive conjunctival response. The results were negative in the rest of the controls. We conclude that the chamomile tea eye washing can induce allergic conjunctivitis. Matricaria chamomilla pollens contained in these infusions are the allergens responsible for these reactions.

Subiza, J., et al. “Allergic conjunctivitis to chamomile tea.” Annals of allergy 65.2 (1990): 127-132.

Dietary intake of the flower extracts of German Chamomile (Matricaria recutita L.) inhibited compound 48/80-induced itch-scratch responses in mice


The antipruritic effects of the diets containing German chamomile on the compound 48/80-induced scratching in ddY mice were examined. Since it is reported that an injection of compound 48/80, but not histamine, induced scratching behaviour due to itch but not to pain in ddY mice (Kuraishi et al., 1995), compound 48/80-induced scratching in ddY mice seems to be a suitable parameter for evaluating antipruritic agents independent of histamine receptor antagonism.

In the mice fed the diet containing 1.2 w/w % of the ethyl acetate extract of dried flower of German chamomile (Matricaria recutita L.) for 11 days, the compound 48/80-induced scratching behaviour was significantly suppressed. The ethyl acetate extract of German chamomile dose dependently suppressed compound 48/80-induced scratching without affecting body weight increase. The ethyl acetate fraction of the ethanol extract and the ethanol extract of hot water extraction residue of German chamomile flower also showed strong inhibition on the compound 48/80-induced scratching. The inhibitory effects of the dietary intake of the German chamomile extracts on compound 48/80-induced itch-scratch response were comparable to oxatomide (10 mg/kg, p.o.), an anti-allergic agent.

Kobayashi, Y., et al. “Dietary intake of the flower extracts of German chamomile (Matricaria recutita L.) inhibited compound 48/80-induced itch-scratch responses in mice.” Phytomedicine 10.8 (2003): 657-664. doi:10.1078/0944-7113-00283

A Metabonomic Strategy for the Detection of the Metabolic Effects of Chamomile (Matricaria recutita L.) Ingestion


A metabonomic strategy, utilizing high-resolution 1H NMR spectroscopy in conjunction with chemometric methods (discriminant analysis with orthogonal signal correction), has been applied to the study of human biological responses to chamomile tea ingestion. Daily urine samples were collected from volunteers during a 6-week period incorporating a 2-week baseline period, 2 weeks of daily chamomile tea ingestion, and a 2-week post-treatment phase. Although strong intersubject variation in metabolite profiles was observed, clear differentiation between the samples obtained before and after chamomile ingestion was achieved on the basis of increased urinary excretion of hippurate and glycine with depleted creatinine concentration. Samples obtained up to 2 weeks after daily chamomile intake formed an isolated cluster in the discriminant analysis map, from which it was inferred that the metabolic effects of chamomile ingestion were prolonged during the 2-week postdosing period. This study highlights the potential for metabonomic technology in the assessment of nutritional interventions, despite the high degree of variation from genetic and environmental sources.

Wang, Yulan, et al. “A metabonomic strategy for the detection of the metabolic effects of chamomile (Matricaria recutita L.) ingestion.” Journal of agricultural and food chemistry 53.2 (2005): 191-196. DOI: 10.1021/jf0403282

Chamomile: A herbal medicine of the past with a bright future


Chamomile is one of the most ancient medicinal herbs known to mankind. It is a member of the Asteraceae/Compositae family and is represented by two common varieties, German Chamomile (Chamomilla recutita) and Roman Chamomile (Chamaemelum nobile). The dried flowers of chamomile contain many terpenoids and flavonoids, which contribute to its medicinal properties. Chamomile preparations are commonly used for many human ailments, including hay fever, inflammation, muscle spasms, menstrual disorders, insomnia, ulcers, wounds, gastrointestinal disorders, rheumatic pain and hemorrhoids. Essential oils of chamomile are used extensively in cosmetics and aromatherapy. Numerous preparations of chamomile have been developed, the most popular being in the form of herbal tea, of which more than one million cups are consumed every day. In this review, we describe the use of chamomile in traditional medicine with regard to evaluating its curative and preventive properties, and highlight recent findings that may contribute to its development as a therapeutic agent promoting human health.

Srivastava, Janmejai K., Eswar Shankar, and Sanjay Gupta. “Chamomile: A herbal medicine of the past with a bright future (Review).” Molecular medicine reports 3.6 (2010): 895-901.

Anti-allergic activity of German chamomile (Matricaria recutita L.) in mast cell mediated allergy model


Ethnopharmacological relevance

Chamomile is most popular used medicinal plant and extensively consumed as a tea or tisanes. Traditionally this plant was used for treatment of many ailments such as allergy disorders and inflammatory mediated diseases.

Aim of the study

We investigated the effects of anti-allergic activity of Matricaria recutita L. on mast cell mediated allergic models.

Materials and methods

The protective effect of methanol extract of Matricaria recutita against compound 48/80 induced anaphylaxis and pruritis models for acute phase of hypersensitivity reactions were carried out. The late phase hypersensitivity reactions by compound 48/80 induced mast cell degranulation and histamine release from blood along with serum nitric oxide (NO), rat peritoneal fluid nitric oxide (NO) and bronchoalveolar fluid nitric oxide (NO) levels were measured.

Chandrashekhar, V. M., et al. “Anti-allergic activity of German chamomile (Matricaria recutita L.) in mast cell mediated allergy model.” Journal of ethnopharmacology 137.1 (2011): 336-340. doi:10.1016/j.jep.2011.05.029

Anaphylactic reaction after the ingestion of chamomile tea: A study of cross-reactivity with other composite pollens


We report a case of an 8-year-old atopic boy in whom ingestion of a chamomile-tea infusion precipitated a severe anaphylactic reaction. The patient suffers from hay fever and bronchial asthma caused by a variety of pollens (grass, olive, and mugwort). This severe reaction was developed after his first ingestion of chamomile tea. Studies revealed the presence of immediate skin test reactivity and a positive passive transfer test to chamomile-tea extract. Moreover, both specific antichamomile-tea extract and anti-Matricaria chamomilla-pollen extract IgE antibodies were detected by an ELISA technique. Cross-reactivity among chamomile-tea extract and the pollens of Matricaria chamomilla, Ambrosia trifida (giant ragweed), and Artemisia vulgaris (mugwort), was demonstrated by an ELISA-inhibition study. These findings suggest a type I IgE-mediated immunologic mechanism as being responsible for the patient’s anaphylactic symptoms and also suggest that the patient cross-reacted the pollens of Matricaria chamomilla contained in the chamomile tea because he was previously sensitized to Artemisia pollen.

Subiza, Javier, et al. “Anaphylactic reaction after the ingestion of chamomile tea: a study of cross-reactivity with other composite pollens.” Journal of allergy and clinical immunology 84.3 (1989): 353-358. doi:10.1016/0091-6749(89)90420-X

In vitro and in vivo studies of natural products: A challenge for their valuation. The case study of chamomile (Matricaria recutita L.)


Medicinal plant research is universally on the rise. Researchers, as well as the general public, recognize that natural products, predominantly those derived from plants, may exhibit health benefits. The tendency is to consider natural products as non-toxic and presenting fewer side effects than those used by conventional medicine. However, information concerning the real human health benefits of natural products is yet seldom available, which is a drawback for their possible valuation. Chamomile is one of the most widely used medicinal plants and its sesquiterpenic-related products are an example of this informative weakness. Several health benefits have been claimed for chamomile extracts and for a large number of sesquiterpenic compounds known to occur in chamomile. However, a deep knowledge concerning the compounds responsible for each specific effect, as well as the mechanisms behind them has not been stated, or, if it exists, is dispersed in literature. Thus, this review comprises a deep survey on the reported potential health benefits of chamomile-related sesquiterpenic compounds, and takes into account the models used for their evaluation: in vitro or in vivo. In spite of the relevance of the in vitro and animal studies reported in literature, where the data obtained are very promising concerning the potential health benefits of chamomile-related sesquiterpenic compounds, their extension to human trials is essential. Several aspects related to this actual challenge are discussed.

Petronilho, Sílvia, et al. “In vitro and in vivo studies of natural products: A challenge for their valuation. The case study of chamomile (Matricaria recutita L.).” Industrial Crops and Products 40 (2012): 1-12. doi:10.1016/j.indcrop.2012.02.041

Cosmeceuticals Containing Herbs: Fact, Fiction, and Future


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Background. Modern medicine is rooted in ethnobotanical traditions using indigenous flora to treat symptoms of human diseases or to improve specific aspects of the body condition. Herbal medicine is now used by over half of the American population. Yet the American medical community generally lacks knowledge of the function, metabolism, interaction, adverse reactions, and preparation of herbal products.

Objective. Because over 60 botanicals are marketed in cosmeceutical formulations, dermatologists need to obtain working knowledge of the major botanicals. The preparation, traditional uses, mechanisms of action, human clinical data, adverse reactions, and interactions all impact herbal efficacy and are discussed below.

Method. English-language medical journal and symposium searches.

Results. The most important botanicals pertaining to dermatologic uses, such as cosmeceuticals, include teas, soy, pomegranate, date, grape seed, Pycnogenol, horse chestnut, German chamomile, curcumin, comfrey, allantoin, and aloe. All are documented to treat dermatologic conditions. Only green and black tea, soy, pomegranate, and date have published clinical trials for the treatment of parameters of extrinsic aging.

Conclusions. Preparation of botanical-based cosmeceuticals is complex. Very few of these products are supported by evidence-based science.

Thornfeldt, Carl. “Cosmeceuticals containing herbs: fact, fiction, and future.” Dermatologic Surgery 31.s1 (2005): 873-881. DOI: 10.1111/j.1524-4725.2005.31734


Clinical cross-reactivity between Artemisia vulgaris and Matricaria chamomilla (chamomile).


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Artemisia vulgaris is a common weed and an important source of allergens on the subtropical island of Tenerife, Canary Islands, Spain. It pollinates mainly from July to September, although, due to some local climatic conditions, it may flower throughout the year. Cross-reactivity with hazelnut, kiwi, birch, several Compositae (Ambrosia, Chrysanthemum, Matricaria, Solidago) and grass allergens has been suggested. Few studies have addressed the issue of in vivo cross-reactivity between A. vulgaris and Matricaria chamomilla. The objective of this study was to perform conjunctival and bronchial challenges with A. vulgaris and M. chamomilla and oral challenge with chamomile in 24 patients with asthma and/or rhinitis sensitized primarily to A. vulgaris. Skin prick tests with M. chamomilla were positive in 21 patients. Eighteen patients had a positive conjunctival provocation test with a A. vulgaris pollen extract and 13 patients had a positive conjunctival provocation test with a M. chamomilla pollen extract. Bronchial provocation tests with A. vulgaris were positive in 15 patients and with M. chamomilla pollen in another 16 individuals. Oral provocation tests, conducted with a commercial chamomile infusion were positive in 13 patients. Nine of these individuals were skin test positive to food allergens and 17 to others pollens of the Compositae family. This study confirms a high degree of in vivo cross-reactivity between A. vulgaris and M. chamomilla. Sensitization to A. vulgaris seems to be a primary risk factor for experiencing symptoms after the ingestion of chamomile infusions. Based on the results of bronchial provocation tests, M. chamomilla pollen could be a relevant inhalant allergen.

de la Torre, Morín F., et al. “Clinical cross-reactivity between Artemisia vulgaris and Matricaria chamomilla (chamomile).” Journal of investigational allergology & clinical immunology 11.2 (2000): 118-122.

Antiproliferative and Apoptotic Effects of Chamomile Extract in Various Human Cancer Cells


Chamomile (Matricaria chamomilla), a popular herb valued for centuries as a traditional medicine, has been used to treat various human ailments; however, its anticancer activity is unknown. We evaluated the anticancer properties of aqueous and methanolic extracts of chamomile against various human cancer cell lines. Exposure of chamomile extracts caused minimal growth inhibitory responses in normal cells, whereas a significant decrease in cell viability was observed in various human cancer cell lines. Chamomile exposure resulted in differential apoptosis in cancer cells but not in normal cells at similar doses. HPLC analysis of chamomile extract confirmed apigenin 7-O-glucoside as the major constituent of chamomile; some minor glycoside components were also observed. Apigenin glucosides inhibited cancer cell growth but to a lesser extent than the parent aglycone, apigenin. Ex vivo experiments suggest that deconjugation of glycosides occurs in vivo to produce aglycone, especially in the small intestine. This study represents the first reported demonstration of the anticancer effects of chamomile. Further investigations of the mechanism of action of chamomile are warranted in evaluating the potential usefulness of this herbal remedy in the management of cancer patients.

Srivastava, Janmejai K., and Sanjay Gupta. “Antiproliferative and apoptotic effects of chamomile extract in various human cancer cells.” Journal of agricultural and food chemistry 55.23 (2007): 9470-9478. DOI: 10.1021/jf071953k


Passion Flower (Passiflora Incarnata) Extract

Preoperative Oral Passiflora Incarnata Reduces Anxiety in Ambulatory Surgery Patients: A Double-Blind, Placebo-Controlled Study


BACKGROUND: Many patients have preoperative anxiety; therefore, the development of a strong anxiolytic with minimal psychomotor impairment for premedication may be desirable.

METHODS: In this study, 60 patients were randomized into two groups to receive either oral Passiflora incarnata (500 mg, Passipy™ IranDarouk) (n = 30) or placebo (n = 30) as premedication, 90 min before surgery. A numerical rating scale (NRS) was used for each patient to assess anxiety and sedation before, and 10, 30, 60, and 90 min after premedication. Psychomotor function was assessed with the Trieger Dot Test and the Digit-Symbol Substitution Test at arrival in the operating room, 30 and 90 min after tracheal extubation. The time interval between arrival in the postanesthesia care unit and discharge to home (discharge time) was recorded for each patient.

RESULTS: The demographic characteristics of patients, ASA physical status, duration of surgery, basal NRS score, sedation at the preset time intervals, and discharge time were similar in the two groups. The NRS anxiety scores were significantly lower in the passiflora group than in the control group (P < 0.001). There were no significant differences in psychological variables in the postanesthesia care unit and recovery of psychomotor function was comparable in both groups.

CONCLUSIONS: In outpatient surgery, administration of oral Passiflora incarnata as a premedication reduces anxiety without inducing sedation.

Movafegh, Ali, et al. “Preoperative oral Passiflora incarnata reduces anxiety in ambulatory surgery patients: a double-blind, placebo-controlled study.” Anesthesia & Analgesia 106.6 (2008): 1728-1732.

Antibacterial properties of Passiflora foetida L. – a common exotic medicinal plant


Passiflora foetida L. (stinking passion flower) is an exotic medicinal vine. The antibacterial properties of leaf and fruit (ethanol and acetone) extracts were screened against four human pathogenic bacteria i.e. Pseudomonas putida, Vibrio cholerae, Shigella flexneri and Streptococcus pyogenes by well-in agar method. The results showed the leaf extract having remarkable activity against all bacterial pathogens compared to fruits. This study supports, the traditional medicines (herbal extracts) to cure many

diseases like diarrhea, intestinal tract, throat, ear infections, fever and skin diseases.

Bewicke, Calverly M. “Dietary supplements containing kava root extract, passion flower, chamomile flowers, hops, and schizandra fruit.” U.S. Patent No. 5,770,207. 23 Jun. 1998.

Passionflower Fruit—A “New” Source of Lycopene?


Many population studies have established a link between dietary intake of the carotenoid antioxidant lycopene and a reduced risk of chronic diseases. Unlike most carotenoids, lycopene occurs in a few places in the diet. Besides tomatoes and tomato products, major sources of lycopene, other lycopene-rich foods include watermelon, pink grapefruit, pink guava, and papaya. Dried apricots and pureed rosehips contain relatively large amounts, too. In our study we found that passionflower fruit (skin and pericarp) contains a great amount of lycopene, whereas the content of other carotenoids is very low, and almost inexistent. This edible fruit could be an alternative source of a potential important nutrient for those people who do not eat tomatoes and tomato products.

Mourvaki, Evangelia, et al. “Passionflower fruit-a” new” source of lycopene?.” Journal of medicinal food 8.1 (2005): 104-106. doi:10.1089/jmf.2005.8.104.

High-Speed Extraction and HPLC Fingerprinting of Medicinal Plants – I. Application to Passiflora Flavonoids


An approach comprising accelerated solvent extraction followed by quantitative HPLC analysis has been adopted in fingerprinting 115 samples of different species of the genus Passiflora. The C-flavonoid glycosides schaftoside (1), isoschaftoside (2), isoorientin (3), orientin (4), isovitexin (5) and vitexin (6) were chosen as analytical standards and their overall prevalence in all samples was determined. The developed HPLC method utilizes gradient elution on an analytical Phenomenex Hypersil ODS column and UV detection at 280 nm. The availability of unique fingerprints, as well as quantitative data, for each species can provide a number of benefits including, but not limited to (a) authentication of samples, (b) determination of chemotaxonomic markers, (c) identification of constituent patterns related to specific geographical locations, (d) supportive data in genetic studies, (e) identifying possible substitutes for Passiflora incarnata, (f) differentiating between closely related species, and (g) relating biological activities to phytochemical profiles.

Rodriguez-Fragoso, Lourdes, et al. “Risks and benefits of commonly used herbal medicines in Mexico.” Toxicology and applied pharmacology 227.1 (2008): 125-135. DOI:10.1076/phbi.

Risks and benefits of commonly used herbal medicines in Mexico


In Mexico, local empirical knowledge about medicinal properties of plants is the basis for their use as home remedies. It is generally accepted by many people in Mexico and elsewhere in the world that beneficial medicinal effects can be obtained by ingesting plant products. In this review, we focus on the potential pharmacologic bases for herbal plant efficacy, but we also raise concerns about the safety of these agents, which have not been fully assessed. Although numerous randomized clinical trials of herbal medicines have been published and systematic reviews and meta-analyses of these studies are available, generalizations about the efficacy and safety of herbal medicines are clearly not possible. Recent publications have also highlighted the unintended consequences of herbal product use, including morbidity and mortality. It has been found that many phytochemicals have pharmacokinetic or pharmacodynamic interactions with drugs. The present review is limited to some herbal medicines that are native or cultivated in Mexico and that have significant use. We discuss the cultural uses, phytochemistry, pharmacological, and toxicological properties of the following plant species: nopal (Opuntia ficus), peppermint (Mentha piperita), chaparral (Larrea divaricata), dandlion (Taraxacum officinale), mullein (Verbascum densiflorum), chamomile (Matricaria recutita), nettle or stinging nettle (Urtica dioica), passionflower (Passiflora incarnata), linden flower (Tilia europea), and aloe (Aloe vera). We conclude that our knowledge of the therapeutic benefits and risks of some herbal medicines used in Mexico is still limited and efforts to elucidate them should be intensified.

Rodriguez-Fragoso, Lourdes, et al. “Risks and benefits of commonly used herbal medicines in Mexico.” Toxicology and applied pharmacology 227.1 (2008): 125-135. doi:10.1016/j.taap.2007.10.005

Passiflora incarnata L.: Ethnopharmacology, clinical application, safety and evaluation of clinical trials


The genus Passiflora incarnata Linnaeus comprises approximately 520 species belonging to the Passifloraceae family. The majority of these species are vines found in Central or South America, with rare occurrence in North America, Southeast Asia and Australia. The genus Passiflora incarnata has long been used in traditional herbal medicine for the treatment of insomnia and anxiety in Europe, and it has been used as a sedative tea in North America. Furthermore, this plant has been used for analgesic, anti-spasmodic, anti-asthmatic, wormicidal and sedative purposes in Brazil; as a sedative and narcotic in Iraq; and for the treatment of disorders such as dysmenorrhoea, epilepsy, insomnia, neurosis and neuralgia in Turkey. In Poland, this plant has been used to treat hysteria and neurasthenia; in America, it has been used to treat diarrhoea, dysmenorrhoea, neuralgia, burns, haemorrhoids and insomnia. Passiflora incarnata L. has also been used to cure subjects affected by opiate dependence in India. This review aims to provide up-to-date information about the pharmacology, clinical efficacy and clinical safety of Passiflora incarnata L. based on the scientific literature. In particular, the methodological accuracy of clinical trials is analysed in accordance with current consolidated guidelines on reporting the clinical efficacy of herbal medicine, offering new insight into opportunities for future research and development.


A bibliographic investigation was performed by examining the available data on Passiflora incarnata L. from globally accepted scientific databases and search engines (Pubmed, Scopus and Web of Science, SciFinder and Google Scholar). We selected studies, case reports, and reviews addressing the pharmacology and safety of Passiflora incarnata.


Although numerous Passiflora incarnata L. derivative products have been commercialised as alternative anxiolytic and sedative remedies based on their long tradition of use, their supposed efficacy does not appear to be adequately corroborated by the literature, with clinical studies often featuring inadequate methodologies and descriptions of the products under investigation. This medicinal plant has shown a wide spectrum of pharmacological activities in preclinical experiments, including anxiolytic, sedative, antitussive, antiasthmatic, and antidiabetic activities. The plant has a good safety profile. The clinical trials that we included in this review were designed to evaluate and in some cases confirm promising observations of preclinical pharmacological activity, and the methodological limits of these studies are characterised here.


In conclusion, clinical studies on the effects of products containing herbal preparations based on Passiflora incarnata reveal crucial weaknesses such as poor details regarding the drug extract ratio, limited patient samples, no description of blinding and randomisation procedures, incorrect definition of placebo, and lack of intention to treat analysis. In conclusion, the results of this review suggest that new clinical trials should be conducted using a more rigorous methodology to assess the traditional putative efficacy of Passiflora incarnata L.

Miroddi, M., et al. “Passiflora incarnata L.: ethnopharmacology, clinical application, safety and evaluation of clinical trials.” Journal of ethnopharmacology 150.3 (2013): 791-804. doi:10.1016/j.jep.2013.09.047

Vegetable extract-based cosmetic or pharmaceutical composition which acts on capillary brittleness


A composition for cosmetic or pharmaceutical use is disclosed. The composition contains a cosmetically or pharmaceutically acceptable carrier, and a combination of vegetable extracts comprising:

(i) a fragon extract (Ruscus aculeatus L.), and

(ii) a sage extract (Salvia officinalis L.).

The composition can be used for the treatment of capillary brittleness by reducing capillary permeability and by increasing capillary resistance.

Aubert, Lucien, and Philippe Anthoine. “Vegetable extract-based cosmetic or pharmaceutical composition which acts on capillary brittleness.” U.S. Patent No. 4,942,033. 17 Jul. 1990.

Passiflora incarnata Linneaus as an anxiolytic before spinal anesthesia



Patients who undergo regional anesthesia experience anxiety in the preoperative period. Passiflora incarnata Linneaus is a plant that has traditionally been used as an anxiolytic and sedative. We aimed to investigate the effect of preoperative oral administration of Passiflora incarnata Linneaus on anxiety, psychomotor functions, sedation, and hemodynamics in patients undergoing spinal anesthesia.


Under local ethics committee approval, 60 patients who were aged 25–55 years and ASAI–II and who were scheduled for spinal anesthesia were enrolled in this prospective, randomized, double-blind and placebo-controlled study. Thirty minutes before spinal anesthesia, baseline hemodynamic parameters, State-Trait Anxiety Inventory (STAI) score, sedation score, and psychomotor function test results were measured, then patients were randomly assigned to two groups: oral Passiflora incarnata Linneaus extract or placebo was given to the patients. Tests were repeated just before spinal anesthesia. Hemodynamics, sedation score, sensory-motor block and side effects were assessed during the operation. Psychomotor function tests were repeated at the end of the operation and 60 min after the operation.


There was a statistically significant difference between the two groups for the increase in State Anxiety Inventory (STAI-S) score obtained just before spinal anesthesia when compared to the baseline. There was no statistically significant difference in psychomotor function from the baseline for either group. A significant difference was not found between the two groups in demographics, psychomotor function, sedation score, hemodynamics, and side effects.


Oral preoperative administration of Passiflora incarnata Linneaus suppresses the increase in anxiety before spinal anesthesia without changing psychomotor function test results, sedation level, or hemodynamics.

Aslanargun, Pınar, et al. “Passiflora incarnata Linneaus as an anxiolytic before spinal anesthesia.” Journal of anesthesia 26.1 (2012): 39-44. DOI



Herbals in the control of ageing


The significance of herbals and herbal products is gaining worldwide recognition. The concept of complementary or alternative medicine is becoming much more widely accepted, and there is an increasing belief in the efficacy of herbal remedies. Recently, the role of herbal drugs, herbal products and certain phytochemicals in the control of ageing has been documented using modern scientific approaches. This review pulls together such studies and critiques the efficacy and value of herbal medicines in the control of the ageing process.

Kapoor, Vijay K., Janhvi Dureja, and Renu Chadha. “Herbals in the control of ageing.” Drug discovery today 14.19 (2009): 992-998. doi:10.1016/j.drudis.2009.06.014


Nervine Herbs for Treating Anxiety


Anxiety is a common ailment in our society. However, the dru

gs available to treat mild-to-moderate anxiety, particularly benzodiazepines, are problematic because they can cause injury, produce side-effects, and create dependence. Nervine herbs have been widely used historically to treat mildto- moderate cases of anxiety, and these herbs appear to be very safe, nonaddictive but their properties as anxiolytics have been poorly researched.


This article discusses the clinical uses of a number of nervines: oat seed (Avena spp.), hawthorn (Crataegus spp.), California poppy (Eschscholzia californica), lavender (Lavandula spp.), chamomile (Matricaria recutita), lemonbalm (Melissa officinalis), passionflower (Passiflora spp.), skullcap (Scutellaria lateriflora), and verbena (also called vervain; Verbena spp.).

Abascal, Kathy, and Eric Yarnell. “Nervine herbs for treating anxiety.” Alternative & Complementary Therapies 10.6 (2004): 309-315. doi:10.1089/act.2004.10.309.


Hydrolyzed Silk Protein

Applications of natural silk protein sericin in biomaterials


Silk sericin is a natural macromolecular protein derived from silkworm Bombyx mori. During the various stages of producing raw silk and textile, sericin can be recovered for other uses. Also, sericin recovery reduces the environmental impact of silk manufacture. Sericin protein is useful because of its properties. The protein resists oxidation, is antibacterial, UV resistant, and absorbs and releases moisture easily. Sericin protein can be cross-linked, copolymerized, and blended with other macromolecular materials, especially artificial polymers, to produce materials with improved properties. The protein is also used as an improving reagent or a coating material for natural and artificial fibers, fabrics, and articles. The materials modified with sericin and sericin composites are useful as degradable biomaterials, biomedical materials, polymers for forming articles, functional membranes,

fibers, and fabrics.

Zhang, Yu-Qing. “Applications of natural silk protein sericin in biomaterials.” Biotechnology advances 20.2 (2002): 91-100. doi:10.1016/S0734-9750(02)00003-4

Silk protein treatment composition and treated substrate for transfer to skin


The present invention relates to a topical delivery system effective in depositing a thin, tenacious and substantially continuous coating of a silk protein on skin by an aqueous emulsion mediated dissolution of protein from a substrate with subsequent transfer and deposition onto the skin. Coatings of silk protein on skin resist removal, thereby providing a protective barrier against chemically- and biochemically-induced skin damage. The treatment composition also provides a vehicle for administering an effective dose of an active agent to the skin surface.

Everhart, Dennis Stein, et al. “Silk protein treatment composition and treated substrate for transfer to skin.” U.S. Patent No. 6,497,893. 24 Dec. 2002.

Attachment and growth of cultured fibroblast cells on silk protein matrices


The attachment and growth of L-929 cells on films made of Bombyx mori silk proteins—fibroin and sericin and their mixtures—was studied by a cell culture method. Both cell attachment and growth were dependent on a minimum of around 90% sericin in the mixture. The results from electron micrography as well as from the DSC measurements supported the notion that the mixture of the two proteins fibroin and sericin has a phase-separated structure in the solid state. The observed minimum of sericin in the cell attachment and growth is thought to be a result of this phase-separated structure. Films of pure component proteins (i.e., 100% fibroin or sericin) exhibited as high a cell attachment and growth as collagen, a widely used mammalian cell culture substrate. However, a morphological study of the attached cells revealed that the cells attached to silk fibroin were extended and had a spindle shape, just like the cells attached to collagen, while the cells attached to the silk sericin had a different shape. It is concluded, therefore, that the attachment condition on silk fibroin is ideal for the viability, growth and function of the cells. © 1995 John Wiley & Sons, Inc.

Minoura, Norihiko, et al. “Attachment and growth of cultured fibroblast cells on silk protein matrices.” Journal of biomedical materials research 29.10 (1995): 1215-1221. DOI: 10.1002/jbm.820291008

Foaming oil gel compositions


A gelled oil composition containing an emulsifier, a gelling agent, an oil, and a surfactant which, when applied to the skin in the presence of water, produces a significant amount of foam. After the composition is rinsed from the skin, a non-greasy, oil residue is left thereon.

Santora, Delores M., John Hopkins, and Laura J. McCulloch. “Foaming cleansers that leave a light, moisturizing feel to the skin after rinsing.” U.S. Patent No. 6,524,594. 25 Feb. 2003.

Contact urticaria from protein hydrolysates in hair conditioners


Protein hydrolysates (PHs) are added to hair-care products (to “repair” broken hair), soaps, bath gels, creams, etc. From one to 22 PHs used in hair-care products (collagen, keratin, elastin, milk, wheat, almond, and silk) were tested in three patient groups: A) 11 hairdressers with hand dermatitis B) 2160 consecutive adults with suspected allergic respiratory disease subjected to routine skin prick tests C) 28 adults with atopic dermatitis.

In group A, all the 22 PHs were tested with scratch and patch tests. In groups B and C, one to three PHs were tested with prick tests. Positive scratch/prick test reactions were seen in 12 patients from three PHs altogether. All were women with atopic dermatitis, and all reacted to at least hydroxypropyl trimonium hydroly:ed collagen (Crotein Q”). In three patients, prick and open tests with a hair conditioner containing Crotein Q were performed with positive results. One patient reported contact urticaria on her hands, and two reported acute urticaria on their head, face, and upper body from a hair conditioner containing Crotein Q. In seven of the eight studied sera, specific IgE to Crotein Q was detected. In conclusion, PHs of hair cosmetics can cause contact urticaria, especially in patients with atopic dermatitis.

Niinimäki, Aila, et al. “Contact urticaria from protein hydrolysates in hair conditioners.” Allergy 53.11 (1998): 1078-1082. DOI: 10.1111/j.1398-9995.1998.tb03818.x

Immediate contact allergy from hydrolyzed wheat in a cosmetic cream


Immediate contact allergy to cosmetics seems to be rare, since only a few case reports on it have been published. We report on a case of IgE-mediated allergic contact urticaria caused by hydrolyzed wheat in a body cream.

Varjonen, Elina, Leena Petman, and Soili Mäkinen‐Kiljunen. “Immediate contact allergy from hydrolyzed wheat in a cosmetic cream.” Allergy 55.3 (2000): 294-296. DOI: 10.1034/j.1398-9995.2000.00516.x

Silk as a biomaterial


Silks are fibrous proteins with remarkable mechanical properties produced in fiber form by silkworms and spiders. Silk fibers in the form of sutures have been used for centuries. Recently regenerated silk solutions have been used to form a variety of biomaterials, such as gels, sponges and films, for medical applications. Silks can be chemically modified through amino acid side chains to alter surface properties or to immobilize cellular growth factors. Molecular engineering of silk sequences has been used to modify silks with specific features, such as cell recognition or mineralization. The degradability of silk biomaterials can be related to the mode of processing and the corresponding content of β-sheet crystallinity. Several primary cells and cell lines have been successfully grown on different silk biomaterials to demonstrate a range of biological outcomes. Silk biomaterials are biocompatible when studied in vitro and in vivo. Silk scaffolds have been successfully used in wound healing and in tissue engineering of bone, cartilage, tendon and ligament tissues.

Vepari, Charu, and David L. Kaplan. “Silk as a biomaterial.” Progress in polymer science 32.8 (2007): 991-1007. doi:10.1016/j.progpolymsci.2007.05.013

Preparation of silk protein sericin as mitogenic factor for better mammalian cell culture


We previously reported that sericin small (sericin-S), with a molecular weight that ranges from 5 to 100 kDa, is a cell culture supplement used to accelerate cell proliferation. In this study, a novel preparation method for sericin and several applications of sericin were examined. Sericin large, prepared under nonhydrolyzing conditions and ranging from 50 to 200 kDa, also accelerated cell proliferation, but its effects were inferior to those of sericin-S. Additional sericin preparations with various molecular weights that were differentially hydrolyzed were also tested but none of them was significantly superior to sericin-S, and neither were several recombinant sericin peptides. Sericin-S successfully accelerated the proliferation of hybridoma cells in various serum-free media, implying the mitogenic effect of sericin is independent from media. We also demonstrated that sericin-S successfully induced the proliferation of CTLL-2, an established T lymphocyte cell line, under IL-2 starvation conditions. These results indicate that sericin, particularly sericin-S, improves serum-free mammalian cell culture.

Terada, Satoshi, et al. “Preparation of silk protein sericin as mitogenic factor for better mammalian cell culture.” Journal of bioscience and bioengineering 100.6 (2005): 667-671. doi:10.1263/jbb.100.667

Skin care preparation


This invention provides skin care compositions which include an emollient complex containing a primary moisturizing agent selected from certain carboxylic acid amides and a mucopolysaccharide secondary moisturizing agent. The compositions also include one or more skin-structuring proteins and an astringent agent which confers skin-firming characteristics. Long lasting protection is afforded by the optional incorporation of a cellulosic film-former. Preferred embodiments take the form of two discrete gel phases.

Schneider, Emil, and James J. Ferone. “Carboxylic acid amide and mucopolysaccharide moisturizers.” U.S. Patent No. 4,973,473. 27 Nov. 1990.

Covalent bonding of active agents to skin, hair or nails


Transglutaminase crosslinks proteins by catalyzing the formation of isopeptide bonds between lysine and glutamine residues. Transglutaminase may be used to crosslink beneficial actives containing an amine moiety to glutamine residues in skin, hair or nails. A variety of beneficial actives, e.g., sunscreens, antimicrobial compounds, skin conditioning agents, hair conditioning agents, anti-inflammatory compounds, antioxidants, coloring agents, perfumes, insect repellants, can thus be delivered to human skin, hair, or nails.

Richardson, Norman K., et al. “Transglutaminase crosslinks proteins by catalyzing the active ingrediants to glutamine residues.” U.S. Patent No. 5,490,980. 13 Feb. 1996.

Retinol Palmitate (Vitamin A Palmitate)

Topical skin cream composition


In a preferred embodiment, a formulation for the treatment of aging skin in which the major active ingredient is glycolic acid in a concentration of from an effective amount up to about 3.5 weight percent. Other active ingredients may be vitamin A palmitate and/or vitamin E acetate. The active ingredients are provided in a moisturizing cream base which has beneficial effects in itself. Preservatives are also provided in the formulation to increase the shelf life thereof.

Jaffery, Manzoor H. “Mixture of carboxy acids, Vitamin A palmitate, Vitamin E acetate, lubricants, humectants for aging skin.” U.S. Patent No. 5,153,230. 6 Oct. 1992.

Characterization of Esterase and Alcohol Dehydrogenase Activity in Skin. Metabolism of Retinyl Palmitate to Retinol (Vitamin A) During Percutaneous Absorption


Retinyl palmitate, a widely used ingredient in cosmetic products, is promoted for its beneficial effects on the appearance of skin. Previous studies suggest that enzymes are available in skin to metabolize this ingredient during skin absorption. Esterase activity hydrolyzes retinyl palmitate to retinol (vitamin A), which is oxidized in many tissues to retinoic acid primarily by alcohol dehydrogenase. The activities of esterase and alcohol dehydrogenase were characterized in hairless guinea pig skin by using flow-through diffusion cells and radiolabeled model compounds (methyl salicylate and benzyl alcohol) previously shown to be metabolized by these enzymes. Methyl salicylate was hydrolyzed by esterase to a greater extent in viable skin than in nonviable skin. Glycine conjugation of salicylic acid and benzoic acid occurred only in viable skin. The metabolism of methyl salicylate and benzyl alcohol occurred to a greater extent in male guinea pig skin than in female guinea pig skin. The percutaneous absorption of both radiolabeled compounds was similar in viable and nonviable skin. About 30 and 18% of topically applied retinyl palmitate were absorbed from an acetone vehicle by hairless guinea pig skin and human skin, respectively. Less than 1% of the applied dose of this lipophilic compound diffused from skin into the receptor fluid. Retinol was the only detectable metabolite of retinyl palmitate in both hairless guinea pig and human skin. In human skin, 44% of the absorbed retinyl palmitate was hydrolyzed to retinol. The use of retinyl palmitate in cosmetic formulations may result in significant delivery of retinol into the skin.

percutaneous absorption metabolism retinyl palmitate hairless guinea pig

Boehnlein, James, et al. “Characterization of esterase and alcohol dehydrogenase activity in skin. Metabolism of retinyl palmitate to retinol (vitamin A) during percutaneous absorption.” Pharmaceutical research 11.8 (1994): 1155-1159. DOI 10.1023/A:1018941016563

Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin


To evaluate the potential use of solid lipid nanoparticles (SLN) in dermatology and cosm

etics, glyceryl behenate SLN loaded with vitamin A (retinol and retinyl palmitate) and incorporated in a hydrogel and o/w-cream were tested with respect to their influence on drug penetration into porcine skin. Conventional formulations served for comparison. Excised full thickness skin was mounted in Franz diffusion cells and the formulations were applied for 6 and 24 h, respectively. Vitamin A concentrations in the skin tissue suggested a certain drug localizing effect. High retinol concentrations were found in the upper skin layers following SLN preparations, whereas the deeper regions showed only very low vitamin A levels. Because of a polymorphic transition of the lipid carrier with subsequent drug expulsion following the application to the skin, the drug localizing action appears to be limited for 6–24 h. Best results were obtained with retinol SLN incorporated in the oil-in-water (o/w) cream retarding drug expulsion. The penetration of the occlusion sensitive drug retinyl palmitate was even more influenced by SLN incorporation. Transepidermal water loss (TEWL) and the influence of drug free SLN on retinyl palmitate uptake exclude pronounced occlusive effects. Therefore enhanced retinyl palmitate uptake should derive from specific SLN effects and is not due to non-specific occlusive properties.

Jenning, Volkhard, et al. “Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin.” European Journal of Pharmaceutics and Biopharmaceutics 49.3 (2000): 211-218. doi:10.1016/S0939-6411(99)00075-2

Unoccluded Retinol Penetrates Human Skin In Vivo More Effectively Than Unoccluded Retinyl Palmitate or Retinoic Acid


The formation of all-trans retinoic acid is an oxidative process whereby retinol is converted to retinaldehyde and then to retinoic acid. Because retinol causes qualitative molecular changes similar to those produced by retinoic acid, we compared potency of retinol, retinaldehyde, and retinyl palmitate to retinoic acid and assessed the effects of occlusion. Retinoids were prepared in an experimental vehicle of 95% ethanol:propylene glycol (7:3) with anti-oxidant. Induction of retinoic acid 4-hydroxylase activity was the end point for comparison. Retinoic acid concentrations from 0.001% to 0.05% under occlusion produced a linear dose-response induction of 4-hydroxylase activity. The concentrations of the other retinoids under occlusion required to achieve significant induction of enzyme activity were 0.6% retinyl palmitate, 0.025% retinol, and 0.01% retinaldehyde. The linear dose-response was lost with retinoid concentrations in excess of 0.25% retinol or 0.5% retinaldehyde. Statistical analyses showed no difference in 4-hydroxylase activity between unocciuded and occluded retinol treated sites. By contrast, however, unoccluded sites treated with retinoic acid or retinyl palmitate had less induction of 4-hydroxylase activity than occluded sites. Retinol, retinaldehyde, and retinyl palmitate did not produce erythema but did increase epidermal thickness. Although retinol is a weaker retinoid than retinoic acid, the increased penetration of unoccluded retinol in comparison to unoccluded retinoic acid with this prototypic vehicle confers on retinol a more effective delivery of a retinoidal effect than unocciuded retinoic acid. Retinol at 0.25% may be a useful retinoid for application without occlusion because it does not irritate but does induce cellular and molecular changes similar to those observed with application of 0.025% retinoic acid.

Duell, Elizabeth A., Sewon Kang, and John J. Voant epithelial tumors by vitamin A acid (retinoic acid)

Prophylaxis of chemically induced benign and malignant epithelial tumors by vitamin A acid (retinoic acid)


The prophylactic effect of retinoic acid on the development of chemically induced papillomas and carcinomas of the skin of mice was examined. The tumors were induced by local application of dimethylbenzanthracene and croton oil. Retinoic acid—200 mg/kg every 14 days—was administered orally during the promotion phase of carcinogenesis. It delayed the appearance, retarded the growth and lead to regression of papillomas. The induction of carcinomas was also inhibited. By prophylactic administration of retinoic acid the appearance of carcinomas was delayed and their incidence reduced.

Bollag, Werner. “Prophylaxis of chemically induced benign and malignant epithelial tumors by vitamin A acid (retinoic acid).” European Journal of Cancer (1965) 8.6 (1972): 689-693. doi:10.1016/0014-2964(72)90153-3

Vitamin A Acid (Retinoic Acid), a Potent Inhibitor of 12-O-Tetradecanoyl-phorbol-13-acetate-induced Ornithine Decarboxylase Activity in Mouse Epidermis1


Topical application of retinoic acid to mouse skin led to a dramatic inhibition of phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate)-induced epidermal ornithine decarboxylase (EC activity, an event proposed to be essential for tumor promotion. The degree of inhibition was dependent on the dose and time of application of retinoic acid. In contrast, treatment with retinoic acid did not depress significantly the phorbol ester-induced S-adenosylmethionine decarboxylase (EC activity, a second enzyme in the pathway of polyamine biosynthesis.

A number of natural vitamin A analogs (retinoids) were tested for their ability to inhibit tetradecanoyl-phorbol-acetate-induced epidermal ornithine decarboxylase activity and were found to be potent in the following order: retinoic acid > retinal > retinol > retinyl acetate > retinyl palmitate. The ability of retinoids to inhibit tetradecanoyl-phorbol-acetate-induced epidermal ornithine decarboxylase activity correlated with their ability to inhibit skin tumor promotion.

Mixing of soluble extracts from tetradecanoyl-phorbol-acetate-treated mouse epidermis pretreated with either retinoic acid or acetone gave essentially additive ornithine decarboxylase activity, arguing against the production of an inhibitor of tetradecanoyl-phorbol-acetate-induced ornithine decarboxylase activity. Furthermore, retinoic acid did not alter tetradecanoyl-phorbol-acetate-induced ornithine decarboxylase activity when added to the assay mixture under normal assay conditions.

Verma, A. K., and R. K. Boutwell. “Vitamin A acid (retinoic acid), a potent inhibitor of 12-O-tetradecanoyl-phorbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis.” Cancer research 37.7 Part 1 (1977): 2196-2201.

Vitamin A and vitamin A palmitate stability over time and under UVA and UVB radiation


Vitamin A and vitamin A palmitate photostability were tested in different media. Ethanol and octyl octanoate solutions of these two vitamins, as such and with the addition of sunscreens (3,4 methylbenzilidencanfora, butyl methoxy dibenzoylmethane and octyl methoxycinnamate) or β-carotene and butylated hydroxy toluene, were analysed spectrophotometrically after UVB or UVA irradiation. An O/W fluid emulsion with 0.5% w/w of retinyl palmitate, with and without butylated hydroxy toluene, was prepared. The oil containing the vitamin was extracted with HCl and aluminium sulfate and analysed spectrophotometrically after UVB or UVA irradiation. The fluid emulsion containing retinyl palmitate with and without butylated hydroxy toluene was stored at different temperatures and analysed every week spectrophotometrically for a month. Of the sunscreens tested butyl methoxy dibenzoylmethane showed the strongest protective action towards vitamin A and vitamin A palmitate, whereas β-carotene did not protect either vitamin. Butylated hydroxy toluene inhibited the photodegradation of both vitamins dissolved in octyl octanoate, suggesting that oxygen may be involved in their degradation. O/W emulsion promoted slightly the degradation of vitamin A ester. Butylated hydroxy toluene protected retinyl palmitate from degradation induced by light and heat.

Carlotti, M. E., V. Rossatto, and M. Gallarate. “Vitamin A and vitamin A palmitate stability over time and under UVA and UVB radiation.” International journal of pharmaceutics 240.1 (2002): 85-94. doi:10.1016/S0378-5173(02)00128-X


A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Retinol Palmitate (Vitamin A) for Symptomatic Chronic Radiation Proctopathy



This study was designed to determine whether oral retinol palmitate (vitamin A) can reduce the symptoms of radiation proctopathy.


A randomized, double-blind trial comparing retinol palmitate (10,000 IU by mouth for 90 days) to placebo was conducted. Eligible patients were more than six months postpelvic radiotherapy and had significant symptoms as measured with the Radiation Proctopathy System Assessments Scale. Nineteen patients were randomized in total: ten to retinol palmitate and nine to placebo. The Radiation Proctopathy System Assessments Scale scores before and every 30 days for 90 days were measured. Five placebo nonresponders were crossed over to the retinol palmitate for another 90 days. Response was defined as a reduction in two or more symptoms by at least two Radiation Proctopathy System Assessments Scale points.


Seven of ten retinol palmitate patients responded, whereas two of nine responded to placebo (P = 0.057). Mean pre-post-treatment change in Radiation Proctopathy System Assessments Scale (Δ Radiation Proctopathy System Assessments Scale) in the retinol palmitate group was 11 ± 5, whereas Δ Radiation Proctopathy System Assessments Scale in the placebo group was 2.5 ± 3.6 (P = 0.013, Mann-Whitney U test). Additionally, all five placebo nonresponders who were crossed over to treatment with retinal palmitate responded to treatment.


In our trial, retinol palmitate significantly reduced rectal symptoms of radiation proctopathy, perhaps because of wound-healing effects. The current results can serve as the foundation for future trials examining retinol palmitate in the multi-institutional setting.

Ehrenpreis, Eli D., et al. “A prospective, randomized, double-blind, placebo-controlled trial of retinol palmitate (vitamin A) for symptomatic chronic radiation proctopathy.” Diseases of the colon & rectum 48.1 (2005): 1-8. DOI 10.1007/s10350-004-0821-7


Aloe Vera Gel

The Effect of Aloe Vera Gel/Mild Soap Versus Mild Soap Alone in Preventing Skin Reactions in Patients Undergoing Radiation Therapy.


Purpose/Objectives: To determine whether the use of mild soap and aloe vera gel versus mild soap alone would decrease the incidence of skin reactions in patients undergoing radiation therapy. Data Sources: Prospective, randomized, blinded clinical trial. Setting: Radiation therapy outpatient clinic in a cancer center affiliated with a major teaching medical facility. Sample: The mean age of the participants was 56 years. The group consisted of Caucasians (74%) and African Americans (26%). The ethnic mix was non-Hispanic (65%) and Hispanic (35%). Methods: Prophylactic skin care began on the first day of radiation therapy. Patients cleansed the area with mild, unscented soap. Patients randomized into the experimental arm of the trial were instructed to liberally apply aloe vera gel to the area at various intervals throughout the day. Findings: At low cumulative dose levels =2,700 cGy, no difference existed in the effect of adding aloe. When the cumulative dose was high (&gt; 2,700 cGy), the median time was five weeks prior to any skin changes in the aloe/soap arm versus three weeks in the soap only arm. When the cumulative dose increases over time, there seems to be a protective effect of adding aloe to the soap regimen. Implications for Nursing Practice: Skin products used to treat radiation dermatitis vary among institutions. Nurses should be aware that some patients may be predisposed to skin problems. Nurses must be aware of newly developed products and research regarding these products so that effective treatment can be instituted.

Olsen, Deborah Lee, et al. “The effect of aloe vera gel/mild soap versus mild soap alone in preventing skin reactions in patients undergoing radiation therapy.” Oncology nursing forum. Vol. 28. No. 3. 2001.

Evaluation of aloe vera gel gloves in the treatment of dry skin associated with occupational exposure


Objective: An examination glove that delivers aloe vera (AV) gel to the gloved hand was studied in 30 adult females with bilateral occupational dry skin with or without irritant contact dermatitis (with or without erythema, fissures, and excoriations). Methods: All participants were factory assembly-line workers with repeated superficial skin trauma who attributed their dry, irritated, emollient-dependent skin to a common cause (occupational exposure). Participants were sequentially enrolled (after written informed consent, n = 29 evaluable participants) into an open, contralateral comparison study to evaluate efficacy of AV glove use 8 h/day to one hand versus no use to the opposite hand for 30 days, followed by 30 days rest, followed by 10 days of repeated use. Participant’s dorsal hands were documented by standardized photos at baseline, during, and at the end of study. Results: Unblinded investigator baseline assessment rated dry skin as mild to moderate (n = 27), or moderate to severe (n = 2). Mean time to noticeable improvement for the AV glove hand was 3.5 days (range: 2-6 days) whereas marked improvement was 10.4 days (range: 7-17 days) for the AV glove hand. No improvement was detected for nonglove hands. Blinded photo assessment was rated independently by dermatology research staff. End-of-study mean global assessment of AV glove hands versus nonglove hands was 1.3 for AV glove hand (0 = no change, 1 = good [10%-89% global improvement], 2 = marked improvement [90%-100% global improvement]) versus 0 for nonglove hand (P <.0001). Mean global end-of-study assessments by the participants = 2.0 for AV glove hand versus 0 for nonglove hand. Conclusion: Dry-coated AV gloves that provide for gradual delivery of AV gel to skin produced a uniformly positive outcome of improved skin integrity, decreased appearance of fine wrinkling, and decreased erythema in the management of occupational dry skin and irritant contact dermatitis. (Am J Infect Control 2003;31:40-2.)

West, Dennis P., and Ya Fen Zhu. “Evaluation of aloe vera gel gloves in the treatment of dry skin associated with occupational exposure.” American Journal of Infection Control 31.1 (2003): 40-42. doi:10.1067/mic.2003.12

The Stimulation of Postdermabrasion Wound Healing with Stabilized Aloe Vera Gel-Polyethylene Oxide Dressing


Full-face dermabrasion provided an ideal opportunity to document the effects of dressings on wound healing management. Following the procedure, the abraded face was divided in half. One side was treated with the standard polyethylene oxide gel wound dressings. The other side was treated with a polyethylene oxide gel dressing saturated with stabilized aloe vera. The polyethylene oxide dressing provided an excellent matrix for the release of aloe vera gel during the initial 5 days of wound healing. By 24–48 hours there was dramatic vasoconstriction and accompanying reduction in edema on the aloe-treated side. By the third to fourth day there was less exudate and crusting at the aloe site, and by the fifth to sixth day the reepithelialization at the aloe site was complete. Overall, wound healing was approximately 72 hours faster at the aloe site. This acceleration in wound healing is important to reduce bacterial contamination, subsequent keloid formation, and/or pigmentary changes. The exact mechanism of acceleration of wound healing by aloe vera is unknown.

FULTON, JAMES E. “The Stimulation of Postdermabrasion Wound Healing with Stabilized Aloe Vera Gel‐Polyethylene Oxide Dressing.” The Journal of dermatologic surgery and oncology 16.5 (1990): 460-467. DOI: 10.1111/j.1524-4725.1990.tb00065.x

Aloe vera leaf gel: a review update


Research since the 1986 review has largely upheld the therapeutic claims made in the earlier papers and indeed extended them into other areas. Treatment of inflammation is still the key effect for most types of healing but it is now realized that this is a complex process and that many of its constituent processes may be addressed in different ways by different gel components. A common theme running though much recent research is the immunomodulatory properties of the gel polysaccharides, especially the acetylated mannans from Aloe vera, which are now a proprietary substance covered by many patents. There have also been, however, persistent reports of active glycoprotein fractions from both Aloe vera and Aloe arborescens. There are also cautionary investigations warning of possible allergic effects on some patients. Reports also describe antidiabetic, anticancer and antibiotic activities, so we may expect to see a widening use of aloe gel. Several reputable suppliers produce a stabilized aloe gel for use as itself or in formulations and there may be moves towards isolating and eventually providing verified active ingredients in dosable quantities

Reynolds, T., and A. C. Dweck. “Aloe vera leaf gel: a review update.” Journal of ethnopharmacology 68.1 (1999): 3-37. doi:10.1016/S0378-8741(99)00085-9

A Phase III Study on the Efficacy of Topical Aloe Vera Gel on Irradiated Breast Tissue


The aim of the study was to see if topical aloe vera gel would be beneficial in reducing the identified skin side-effects of radiation therapy, including erythema, pain, itching, dry desquamation, and moist desquamation, when compared with aqueous cream. The secondary aim was to assess the effect of other factors known to predict severity of radiation skin reaction, ie, breast size, smoking habit, and one or more drainages of lymphocele after surgery, on other skin side effects.

A Phase III study was conducted involving 225 patients with breast cancer after lumpectomy or partial mastectomy, who required a course of radiation therapy using tangential fields. Patients were randomized to either topical aloe vera gel or topical aqueous cream to be applied 3 times per day throughout and for 2 weeks after completion of radiation treatment. Weekly skin assessments were performed by nursing staff.

Aqueous cream was significantly better than aloe vera gel in reducing dry desquamation and pain related to treatment. Subjects with D cup or larger size breasts experienced significantly more erythema, regardless of treatment arm. For subjects who had undergone lymphocele drainage, the aloe vera group experienced significantly more pain than the aqueous cream group. Within the aqueous cream arm, smokers were significantly more likely to experience itching within the treatment field than were nonsmokers. Within the aloe vera arm, subjects who had undergone one or more lymphocele drainages after surgery were significantly more likely to experience erythema and itching within the treatment field than those who did not have drainage.

In this study, aloe vera gel did not significantly reduce radiation-induced skin side effects. Aqueous cream was useful in reducing dry desquamation and pain related to radiation therapy.

Heggie, Sue, et al. “A phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue.” Cancer nursing 25.6 (2002): 442-451.

Aloe Vera for Preventing Radiation-induced Skin Reactions: A Systematic Literature Review



To systematically review and critically appraise the evidence for effectiveness of Aloe vera gel for radiation-induced skin reactions.

Materials and methods

Major biomedical databases and specialist complementary and alternative medicine databases were searched. Additionally, efforts were made to identify unpublished and ongoing research. Relevant research was systematically categorised by study type and appraised according to study design. Clinical commentaries were obtained for each study included in the review.



One earlier systematic review on Aloe vera for a variety of conditions was located. Five published randomised-controlled trials (RCTs) were found, along with two additional RCTs that are not published. No non-RCTs, uncontrolled studies or qualitative studies were found.



There is no evidence from clinical trials to suggest that topical Aloe vera is effective in preventing or minimising radiation-induced skin reactions in cancer patients. Further methodologically rigorous, sufficiently powered research studies should be conducted to evaluate the effectiveness of currently used and novel therapies for the prevention, minimisation and management of radiation-induced skin reactions.

Richardson, Janet, et al. “Aloe vera for preventing radiation-induced skin reactions: a systematic literature review.” Clinical Oncology 17.6 (2005): 478-484. doi:10.1016/j.clon.2005.04.013

Quality and authenticity of commercial aloe vera gel powders


This study provides a survey of commercial aloe vera gel powders. Nine products, obtained from leading international suppliers, were examined and compared with fresh aloe vera gel. A multi-technique approach was chosen to assess their quality and authenticity. Authenticity was evaluated by nuclear magnetic resonance spectrometry (1H NMR). The absence of adulterants, impurities, and preservatives was also investigated by this technique. The amount of mannose after acid hydrolysis gave a direct and rapid measurement of the concentration of the polysaccharide acemannan in the gel powder. The quality of the samples analysed was found to be very inconsistent and in some cases extremely poor. Only three products, out of the nine analysed, contained satisfactory amounts of acemannan (ca. 10%, w/w) whereas the remaining samples exhibited very low levels. Two samples only contained ca. 1% (w/w). Four samples showed a high degree of enzymatic degradation and bacterial fermentation. One contained an abnormally high concentration of free glucose (ca. 30%, w/w). An HPLC–UV method was set up to verify the absence of hydroxyanthracene derivatives (aloin and aloin-related compounds). Aloin A was found to be present at concentrations from trace levels to ca. 16 mg/kg.

Bozzi, A., et al. “Quality and authenticity of commercial aloe vera gel powders.” Food chemistry 103.1 (2007): 22-30. doi:10.1016/j.foodchem.2006.05.061

Investigation of the Anti-Inflammatory Potential of Aloe vera Gel (97.5%) in the Ultraviolet Erythema Test


Background:Aloe vera is a natural product that is frequently used in soothing skin care products such as aftersun lotions. In the present study we aimed to explore the anti-inflammatory potential of a highly concentrated A. vera gel in the UV erythema test in vivo. Methods: 40 volunteers with skin types II and III were included in the randomized, double-blind, placebo-controlled, phase III monocenter study. Test areas on the back were irradiated with the 1.5-fold minimal erythema dose of UVB. Subsequently, the test areas were treated occlusively on 2 subsequent days with A. vera gel (97.5%), the positive controls (0.25% prednicarbate, 1% hydrocortisone in placebo gel and 1% hydrocortisone cream) and a placebo gel. Erythema values were determined photometrically after 24 and 48 h. Results:A. vera gel (97.5%) significantly reduced UV-induced erythema after 48 h, being superior to 1% hydrocortisone in placebo gel. In contrast, 1% hydrocortisone in cream was more efficient than A. vera gel. Conclusions: In this study after 48 h the A. vera gel (97.5%) displayed some anti-inflammatory effects superior to those of 1% hydrocortisone in placebo gel. The A. vera gel tested here might be useful in the topical treatment of inflammatory skin conditions such as UV-induced erythema.

Reuter, J., et al. “Investigation of the anti-inflammatory potential of Aloe vera gel (97.5%) in the ultraviolet erythema test.” Skin pharmacology and physiology 21.2 (2008): 106-110.

Influence of Aloe vera on collagen characteristics in healing dermal wounds in rats


Wound healing is a fundamental response to tissue injury that results in restoration of tissue integrity. This end is achieved mainly by the synthesis of the connective tissue matrix. Collagen is the major protein of the extracellular matrix, and is the component which ultimately contributes to wound strength. In this work, we report the influence of Aloe vera on the collagen content and its characteristics in a healing wound. It was observed that Aloe vera increased the collagen content of the granulation tissue as well as its degree of crosslinking as seen by increased aldehyde content and decreased acid solubility. The type I/type III collagen ratio of treated groups were lower than that of the untreated controls, indicating enhanced levels of type III collagen. Wounds were treated either by topical application or oral administration of Aloe vera to rats and both treatments were found to result in similar effects.

Chithra, Pandarinathan, G. B. Sajithlal, and Gowri Chandrakasan. “Influence of Aloe vera on collagen characteristics in healing dermal wounds in rats.” Molecular and cellular biochemistry 181.1-2 (1998): 71-76. DOI 10.1023/A:1006813510959

Moisturizing effect of cosmetic formulations containing Aloe vera extract in different concentrations assessed by skin bioengineering techniques


Background/purpose: The polysaccharide-rich composition of Aloe vera extracts (Aloe barbadensis Miller), often used in cosmetic formulations, may impart moisturizing properties to the product. The aim of this study was to evaluate the effect of cosmetic formulations containing different concentrations of freeze-dried Aloe vera extract on skin hydration, after a single and a 1- and 2-week period of application, by using skin bioengineering techniques.

Methods: Stable formulations containing 5% (w/w) of a trilaureth-4 phosphate-based blend were supplemented with 0.10%, 0.25% or 0.50% (w/w) of freeze-dried Aloe vera extract and applied to the volar forearm of 20 female subjects. Skin conditions in terms of the water content of the stratum corneum and of transepidermal water loss (TEWL) (CorneometerTM CM 825 and TewameterTM TM 210) were analysed before and after a single and 1- and 2-week period of daily application.

Results: After a single application, only formulations supplemented with 0.25% and 0.50% (w/w) of Aloe vera extract increased the water content of the stratum corneum, while after the 2-week period application, all formulations containing the extract (0.10%, 0.25% and 0.50%) had the same effect, in both cases as compared with the vehicle. TEWL was not modified after a single and after 1- and 2-week period of application, when compared with the vehicle.

Conclusion: Our results show that freeze-dried Aloe vera extract is a natural effective ingredient for improving skin hydration, possibly through a humectant mechanism. Consequently, it may be used in moisturizing cosmetic formulations and also as a complement in the treatment of dry skin.

Dal’Belo, Susi Elaine, et al. “Moisturizing effect of cosmetic formulations containing Aloe vera extract in different concentrations assessed by skin bioengineering techniques.” Skin Research and Technology 12.4 (2006): 241-246. DOI: 10.1111/j.0909-752X.2006.00155.x

Tocopheryl Acetate

Comparison of alpha-tocopheryl nicotinate and acetate on skin microcirculation


Clinical observations were made on persons with microcirculatory disturbances after administration of α-tocopheryl nicotinate. It was observed that the clinical symptoms of severe acrocyanosis and “feeling cold” were cured. All subjects were given the cooling-rewarming test. The experimental results indicated the tocopheryl nicotinate had strong effects on the microcirculation of the hand. The data show that α-tocopheryl nicotinate was more effective than the α-tocopheryl acetate and a mixture of α-tocopheryl acetate and nicotinic acid in reducing the mean rewarming time and that the effectiveness of α-tocopheryl nicotinate was not due to the synergic action of the tocopherol and nicotinic acid, but to the independent action of α-tocopheryl nicotinate.

Kamimura, Mitsuo. “Comparison of alpha-tocopheryl nicotinate and acetate on skin microcirculation.” The American journal of clinical nutrition 27.10 (1974): 1110-1116.

Topical application of α-tocopherol modulates the antioxidant network and diminishes ultraviolet-induced oxidative damage in murine skin


The aim of this study was to investigate the effects of topical α-tocopherol application on epidermal and dermal antioxidants and its ability to prevent ultraviolet (UV)-induced oxidative damage. Hairless mice received topical applications of α-tocopherol 24 h before a single, acute UV irradiation (10 × minimal erythemal dose). The four major antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase), hydrophilic and lipophilic antioxidants, and lipid hydroperoxides, markers of oxidative damage, were assayed in both epidermis and dermis of hairless mice. Topical α-tocopherol treatment increased dermal superoxide dismutase activity by 30% (P < 0.01) and protected epidermal glutathione peroxidase and superoxide dismutase from depletion after UV irradiation. Total and reduced glutathione levels in the epidermis increased by 50% after the topical treatment (P < 0.05), as did dermal ascorbate levels (by 40%; P < 0.01). The topical treatment increased α-tocopherol levels both in the epidermis (62-fold) and the dermis (22-fold; P < 0.001 in each layer). Furthermore, α-tocopherol treatment significantly reduced the formation of epidermal lipid hydroperoxides after UV irradiation (P < 0.05). These results demonstrate that topical administration of α-tocopherol protects cutaneous tissues against oxidative damage induced by UV irradiation in vivo, and suggest that the underlying mechanism of this effect involves the up-regulation of a network of enzymatic and non-enzymatic antioxidants.

Lopez-Torres, M., et al. “Topical application of -tocopherol modulates the antioxidant network and diminishes ultraviolet-induced oxidative damage in murine skin.” British Journal of Dermatology 138.2 (1998): 207-215. DOI: 10.1046/j.1365-2133.1998.02062.x

Incidence of squamous cell carcinoma in hairless mice irradiated with ultraviolet light in relation to intake of ascorbic acid (vitamin C) and of D, L-alpha-tocopheryl acetate (vitamin E).


We have carried out a study of large malignant skin tumours (squamous-cell carcinomas) and other lesions in “hairless” mice (in groups of 45 or 60 mice) intermittently exposed to ultraviolet light over a period of 15 weeks, beginning when the mice were about 8 weeks old. Various groups were given a standard diet (Wayne Lab-Blox) or the same food with added vitamin C or vitamin E throughout the study. Lesions, classified by histopathologic study as atypical squamous-cell proliferations varying from early actinic keratoses to invasive poorly differentiated squamous-cell carcinomas, had begun to develop by the end of the period of irradiation. They were counted twice a month for five months. The observed fraction of mice that developed lesions during successive time periods was analyzed by the statistical method recommended by a committee of the International Agency for Research on Cancer. A pronounced effect of vitamin C in decreasing the incidence of the malignant lesions was observed with very high statistical significance. No significant effect of vitamin E was observed. We conclude that vitamin C should be given special attention with respect to the relation between diet and cancer.

Pauling, L., et al. “Incidence of squamous cell carcinoma in hairless mice irradiated with ultraviolet light in relation to intake of ascorbic acid (vitamin C) and of D, L-alpha-tocopheryl acetate (vitamin E).” International journal for vitamin and nutrition research. Supplement= Internationale Zeitschrift fur Vitamin-und Ernahrungsforschung. Supplement 23 (1981): 53-82.



Abstract— The photoprotective effect of topically applied α-tocopheryl acetate (vitamin E acetate), a stable derivative of α-tocopherol (vitamin E), and its possible bioconversion to the active antioxidant species (α-tocopherol) was examined in skin tissue of female hairless mice (HRS/J) exposed to UV-B irradiation. Our results indicate that topically applied α-tocopheryl acetate is absorbed into and retained by skin tissue. Furthermore, skin tissue from UV-B-irradiated animals that received daily topical α-tocopheryl acetate treatments contained significantly higher levels (P < 0.001) of α-tocopheryl acetate than non-UV-B-irradiated mice that received identical daily topical α-tocopheryl acetate treatments. Finally, free α-tocopherol levels in skin also were significantly increased (P < 0.00 1) by topical applications of α-tocopheryl acetate and skin levels of free α-tocopherol were significantly greater (P < 0.001) in UV-B-irradiated animals that received daily topical α-tocopheryl acetate treatments than in non-UV-Birradiated animals. These results suggest that UV-B irradiation enhances both the absorption of α-tocopheryl acetate and its bioconversion to free α-tocopherol.

Norkus, E. P., G. F. Bryce, and H. N. Bhagavan. “Uptake and Bioconversion of α‐Tocopheryl Acetate to α‐Tocopherol in Skin of Hairless Mice.” Photochemistry and photobiology 57.4 (1993): 613-615. DOI: 10.1111/j.1751-1097.1993.tb02926.x

Hydrolysis of RRR-α-tocopheryl acetate (vitamin E acetate) in the skin and its UV protecting activity (an in vivo study with the rat)


Vitamin E acetate is often used rather than vitamin E as an ingredient of skin care products and dermatological preparations, because it lacks the free phenolic OH group. However, because of this the acetate as such is biologically inactive. In spite of this intrinsic inactivity, the skin is protected against the harmful effects of sunlight after topical application of vitamin E acetate. Therefore it is supposed that hydrolysis takes place in the skin and that the reaction product, the radical scavenger vitamin E, is responsible for the protection observed.

In this in vivo study with the rat, we have investigated the hydrolysis of RRR-α-tocopheryl acetate (vitamin E acetate) in the epidermis in relation to UV radiation protection. (As a measure of protection, we used the UV-induced binding of 8-methoxypsoralen to epidermal biomacromolecules.)

After a period of 5 h from a single application of vitamin E acetate, hydrolysis into free vitamin E was not observed. No protection was found at this time point, corresponding with the absence of vitamin E.

After treatment for 5 days, consisting of one topical application daily, the percentage of acetate present in the stratum corneum which was hydrolysed into free vitamin E was less than 1%, whereas the corresponding value for the viable layer of the epidermis was about 5%.

The hydrolysis of vitamin E acetate in the epidermis proceeded very slowly. As a result, the absolute amount of free vitamin E, found in the total epidermis after treatment for 5 days with the acetate, was only a few times higher than the normal level. Yet, this very small amount of free vitamin E proved to be sufficient for maximal protection in this animal model.

The results show that vitamin E acetate acts as a prodrug, which very slowly releases minute amounts of active vitamin E.

van Henegouwen, Gerard MJ Beijersbergen, Hans E. Junginger, and Henk de Vries. “Hydrolysis of RRR-α-tocopheryl acetate (vitamin E acetate) in the skin and its UV protecting activity (an in vivo study with the rat).” Journal of Photochemistry and Photobiology B: Biology 29.1 (1995): 45-51. doi:10.1016/1011-1344(95)90251-1


Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice


Exposure of the skin of the back of skh-1 hairless mice to UVB (310 nm peak) irradiation at doses of 0.115–0.23 J/cm2 results after 24–48 h in an erythema which can be quantified using an erythema meter, providing a useful model of sunburn. Application of pure d-α-tocopherol acetate, a thick oil, to the skin immediately following the exposure to UVB significantly reduces the increase in erythema index, by 40–55%. At the lower dose (0.115 J/cm2), skin thickness (associated with edematous swelling of the sunburned skin) was measured by a novel noninvasive technique not previously reported for this purpose—magnetic resonance imaging (MRI). In two experiments the UVB-induced increase in skin thickness was significantly reduced at 24 hr by 29 and 54%, and at 48 hr by 26 and 61%. After 8 days the untreated irradiated mouse skin still showed a significant increase in thickness (24%) compared to the untreated unirradiated control, while the treated irradiated control was not significantly thicker than the unexposed control. Skin sensitivity was tested using a modification of the technique of esthesiometry, by observing rapid avoidance responses of the mouse to a pressure of 0.96 g/cm2 exerted by applying to the skin the tip of a nylon esthesiometer fiber extended to 60 mm in length. The untreated irradiated mice were more sensitive (p < 0.07, Wilcoxon test) than the treated irradiated mice, and also significantly different from the untreated unirradiated control mice (p < 0.04, Wilcoxon test), but the treated irradiated mice were not significantly differently sensitive when compared to the unirradiated controls (p < 0.32). Taken together these data indicate that the erythema, edema, and skin sensitivity commonly associated with UVB-induced sunburn are significantly reduced by topical application of tocopherol acetate even after the exposure has occurred. This observation suggests that treatment of sunburn may be possible even after the irradiation has stopped, by a derivative of d-α-tocopherol which is stable to autooxidation.

Trevithick, John R., et al. “Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice.” Archives of biochemistry and biophysics 296.2 (1992): 575-582. doi:10.1016/0003-9861(92)90613-2

The influence of dietary lipid source and alpha-tocopheryl acetate level on product quality of rainbow trout (Salmo gairdneri)


Rainbow trout (Salmo gairdneri) were fed practical diets containing either fish oil or swine fat and supplemented with 0, 50, 500, or 1500 mg of alpha-tocopheryl acetate per kg of diet for 4 months prior to harvest. The effects of diet on sensory attributes, fatty acid composition, tissue alpha-tocopherol level, and lipid oxidation during forzen storage were determined. Dietary fat source or alpha-tocopheryl acetate did not significantly affect sensory attributes of trout fillets evaluated fresh or after prolonged frozen storage. The fatty acid composition of the muscle and viscera were influenced by dietary fat source, most markedly in the levels of n−3 and n−6 fatty acids. Tissue alpha-tocopherol levels were significantly increased at dietary levels of 500 and 1500 mg alpha-tocopheryl acetate per kg diet. The dietary level of alpha-tocopheryl acetate required to prevent vitamin E deficiency signs was higher in fish fed the fish oil diet than in the fish fed the swine fat diet. Fish fed diets containing 500 and 1500 mg alpha-tocopheryl acetate had lower levels of malonaldehyde after frozen storage at −80°C for 4 months, but not after frozen storage at −20°C for 10 months.

Boggio, Steven M., et al. “The influence of dietary lipid source and alpha-tocopheryl acetate level on product quality of rainbow trout (Salmo gairdneri).” Aquaculture 51.1 (1985): 13-24. doi:10.1016/0044-8486(85)90236-4

Inhibitory effects of glutathione level-raising agents and D-α-tocopherol on ornithine decarboxylase induction and mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate


The constituent amino acids of reduced glutathione (GSH), GSH itself, and D-α-tocopherol inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC, L-omithine carboxy-lyase, EC activity in mouse epidermis in vivo and in vitro. The inhibitory effects of cysteine (Cys), GSH and D-α-tocopherol on ODC induction were proportional to their abilities to decrease the incidence of skin tumors in the initiation-promotion protocol. Moreover, the ability of the constituent amino acids of GSH and GSH to inhibit TPA-induced ODC activity correlated well with their ability to increase the ratio of GSW/oxidized glutathione (GSSG) in isolated epidermal cells. In vitro, various treatments with 1 mM GSH, 1 mM glutamic acid (Glu), 1 mM glycine (Gly), 0.4 mM Cys and/or 0.2 mM cystine (CysCys) inhibited dramatically the sharp decline in the intracellular ratio of GSH/GSSG caused by 0.1 μM TPA. Since the inhibitory effects of Cys on both the decrease in the ratio of GSH/GSSG and the induction of ODC activity by TPA were greatly reduced by the inhibitors of γ-glutamyl transpeptidase and γ-glutamylcysteine synthetase, it is suggested that some of the inhibitory effects of Glu, Cys and Gly on tumor promotion could result from their interference with the metabolism of the tripeptide GSH, a natural antioxidant which inhibits chemical carcinogenesis. The free radical scavenger D-α-tocopherol, which did not alter directly the intracellular ratio of GSH/GSSG, also prevented completely the decrease in the ratio of GSH/GSSG caused by TPA. These results, therefore, suggest that GSH level-raising agents and other antioxidants might inhibit by diverse means the effects of TPA on GSH metabolism and skin tumor promotion.

Perchellet, Jean-Pierre, et al. “Inhibitory effects of glutathione level-raising agents and D-α-tocopherol on ornithine decarboxylase induction and mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.” Carcinogenesis 6.4 (1985): 567-573. doi: 10.1093/carcin/6.4.567

The role of vitamin E in normal and damaged skin


The generation of free oxygen radicals is believed to play an important pathogenic role in the development of various disorders. More than other tissues, the skin is exposed to numerous environmental chemical and physical agents such as ultraviolet light causing oxidative stress. In the skin this results in several short- and long-term adverse effects such as erythema, edema, skin thickening, wrinkling, and an increased incidence of skin cancer or precursor lesions. However, accelerated cutaneous aging under the influence of ultraviolet light, usually termed photoaging, is only one of the harmful effects of continual oxygen radical production in the skin. Others include cutaneous inflammation, autoimmunological processes, keratinization disturbances, and vasculitis. Vitamin E is the major naturally occurring lipid-soluble non-enzymatic antioxidant protecting skin from the adverse effects of oxidative stress including photoaging. Its chemistry and its physiological function as a major antioxidative and anti-inflammatory agent, in particular with respect to its photoprotective, antiphotoaging properties, are described by summarizing animal studies, in vivo tests on human skin and biochemical in vitro investigations. The possible therapeutic use in different cutaneous disorders, and pharmacological and toxicological aspects are discussed. Many studies document that vitamin E occupies a central position as a highly efficient antioxidant, thereby providing possibilities to decrease the frequency and severity of pathological events in the skin. For this purpose increased efforts in developing appropriate systemic and local pharmacological preparations of vitamin E are required.

Nachbar, F., and H. C. Korting. “The role of vitamin E in normal and damaged skin.” Journal of Molecular Medicine 73.1 (1995): 7-17. DOI 10.1007/BF00203614

Tocopheryl acetate nanoemulsions stabilized with lipid–polymer hybrid emulsifiers for effective skin delivery


Tocopheryl acetate is used as the oil component of nanoemulsions using a mixture of unsaturated phospholipids and polyethylene oxide-block-poly(ɛ-caprolactone) (PEO-b-PCL). This study investigates the effects of the lipid–polymer composition on the size and surface charge of nanoemulsions, microviscosity of the interfacial layer, and skin absorption of tocopheryl acetate. The lipid–polymer hybrid system exhibits excellent colloidal dispersion stability, which is comparable to that of polymer-based nanoemulsions. If lipids are used as emulsifiers, nanoemulsions show poor dispersion stability despite a good skin absorption enhancing effect. The amount of tocopheryl acetate absorbed by the skin increases with an increased lipid-to-polymer ratio, as determined using the hairless guinea pig skin loaded in a Franz-type diffusion cell. An 8:2 (w/w) mixture of unsaturated phospholipids and PEO-b-PCL exhibits the most efficient delivery of tocopheryl acetate into the skin. Our results show that tocopheryl acetate is absorbed almost twice as fast by the lipid–polymer hybrid system than the nanoemulsions stabilized with PEO-b-PCL. This study suggests that the lipid–polymer hybrid system can be used as an effective means of optimizing nanoemulsions in terms of dispersion stability and skin delivery capability.

Nam, Yoon Sung, et al. “Tocopheryl acetate nanoemulsions stabilized with lipid–polymer hybrid emulsifiers for effective skin delivery.” Colloids and Surfaces B: Biointerfaces 94 (2012): 51-57. doi:10.1016/j.colsurfb.2012.01.016