P6142A natural biotechnologic active ingredient dedicated to skin troublemanagement

Caroline Baudouin, Laboratoires Expanscience, Epernon, French Guiana;Alex Saunois, Laboratoires Expanscience, Epernon, France; Johan Rocheteau,Laboratoires Expanscience, Epernon, France; Philippe Msika, LaboratoiresExpanscience, Epernon, France; Sebastien Debrock, Laboratoires Expanscience,Epernon, France; Sophie Leclere-Bienfait, Laboratoires Expanscience, Epernon,France

Background: The proteinase-activated receptor-2 (PAR-2) is a G-protein coupledreceptor that can be activated by a variety of proteinases (endogenous or producedby allergens and pathogens). PAR-2 is abundantly expressed in the skin. Over time,numerous studies and data allowed to confirm the role of PAR-2 in skin physiologybut also in skin pathology and suggest that PAR-2 might be a potent therapeutictarget. We have developed specific peptides from an original vegetal source ofprotein, quinoa (Chenopodium quinoa). This active ingredient was developedaccording a biotechnological process, in compliance with our sustainable policy.The final and patented ingredient is secured and optimized containing a highpeptides concentration at specific molecular weights distribution.

Methods: Normal human epidermal keratinocytes (NHEKs) were incubated withquinoa peptides. Gene expressions of PAR-2, keratin 1, keratin 10, loricrin,involucrin, and desmoglein-1 were evaluated by RT-PCR. Hyaluronic acid andGAGs production was assessed respectively by ELISA and by measuring radiolabeledsulfate. After quinoa peptides’ pretreatment, NHEKs were stimulated by PMA andinflammatory mediators was measured by ELISA. NF-kappaB nuclear translocationwas followed by immunofluorescent staining. Mast cells were stimulated bysubstance P; histamine release was quantified by ELISA.

Results: As gene expression of PAR-2 (-30%) was reduced by these natural patentedpeptides, their in vitro effects on cutaneous inflammationwere investigated. Quinoapeptides were able to significantly reduce aspecific inflammatory mediators: IL-1alfa(basal level), IL-8 (-61%), PGE2 (-94%), VEGF (-49%), and NF-kappaB (translocationinhibition) and to limit neurogenic inflammation in mast cells (histamine; -84%).Second, we have evaluated the quinoa peptides activity on skin barrier. Geneexpressions of differentiation, cornified envelope and corneodesmosome markerswere significantly stimulated: K1, K10 (X7, X3.5), loricrin, involucrin (X2.8, X1.3),and desmoglein-1 (X2.8). The moisturizing factors, hyaluronic acid (+149%) andGAGs (+32%), were highly enhanced by quinoa peptides.

Conclusion: Patented quinoa peptides from natural biotechnology have shown aspecific and wide spectrum of activity on inflammation and skin barrier. They couldbe of interest in the management of skin troubles involving PAR-2 such as pruritus,skin hyperreactivity and allergy, atopic dermatitis, acne, and hyperpigmentation.

APRIL 20

cial support: None identified.

Commer

P6907Antimycotic activity and penetration through bovine hoof membranes ofan innovative terbinafine nail solution (P-3058)

Federico Mailland, MD, Scientific Dept., Polichem SA, Lugano Pazzallo,Switzerland; Anna Bulgheroni, MS, Scientific Dept., Polichem SA, LuganoPazzallo, Switzerland

The aim of our study was to investigate: (1) the antimycotic activity versusonychomycosis pathogens and (2) the penetration through bovine hoof mem-branes as a biologic model of human nail permeation by a new proprietarytechnology of nail solutions (P-3058) based on hydroxypropyl chitosan (HPCH) asthe film forming agent and terbinafine as the sole active ingredient. Total growthinhibition has been determined for Candida parapsilosis, Trichophyton rubrum, and Scopulariopsis brevicaulis through broth dilution susceptibility testing,NCCLS M27-A and M38-A. Dilutions were made as follows: P-3058 8% (w/wconcentration range: 0.8%-0.025%); P-3058 4% (0.4%-0.012%); P-3058 1% (0.1%-0.0003%). Reference HPCH vehicle was also investigated. Total inhibition offungal growth for C parapsilosis was 0.05% with a range from 0.025% to 0.05%.For S brevicaulis, total inhibition occurred in the range of 0.025% to 0.2%. For Trubrum, total inhibition was achieved at less than or equal to the least testedconcentration, respectively. According to agar diffusion assays, Sabourauddextrose agar square plates were inoculated with each of the test strains(C parapsilosis, S brevicaulis, T mentagrophytes var. interdigitale, and Trubrum). A neutral disk with 10 �L of P-3058, and 3 bovine hoof slices with10 �L P-3058, 20 �L P-3058, and 10 �L vehicle were put on each plate. Theexperiments were repeated with P-3058 at 0.5%, 1%, and 2% concentrations ofterbinafine. The bovine nail slices had 75 �m of thickness. Plates were inoculatedat 32 6 18C for at least 5 days. At the end of the inoculation period, anassessment of fungal growth was done by measuring the inhibition rings for eachof the 4 strains and for each P-3058 tested concentration. The results of the studyshowed that P-3058 produced concentration- and dose-dependent inhibition ringsof the tested strains. Vehicle did not show any inhibition. Inhibition rings aroundneutral disks were expected, considering the antifungal action of terbinafine,whereas the inhibition rings obtained around nail slices were consequence ofactive release from the new formulation and penetration through nail slices aswell as diffusion into agar.

nsored by Polichem SA.

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P6892Delivery of stearic acid to scalp stratum corneum from zinc pyrithioneshampoo

Jane Matheson, PhD, Unilever R&D, Bebington, United Kingdom; Amy Qualls,Unilever R&D, Trumbull, CT, United States; Elizabeth Cox, Unilever R&D,Trumbull, CT, United States; Fiona Baines, PhD, Unilever R&D, Bebington,United Kingdom; Lynette Weddell, Unilver R&D, Bebington, United Kingdom;Sarah Paterson, MS, Unilever R&D, Bebington, United Kingdom

Background: Washing skin with a liquid cleanser base can reduce the level of fattyacids, such as stearic acid, in the skin, resulting in skin damage. New cleansingtechnologies have been developed that have the ability to deliver stearic acid intothe stratum corneum.

Objective: To evaluate the penetration of d35-stearic acid into scalp stratumcorneum from zinc pyrithione shampoo formulations (male and female variants)after a single wash.

Methods: The studywas of awhole-head, controlled application design. Subjects (22females and 22 males) underwent a 1-week conditioning phase during which amarketed beauty shampoo was used. They then had their hair washed at the testcenter by trained staff with the appropriate zinc pyrithione shampoo containingdeuterated stearic acid. Stratum corneum samples were collected by taking 10sequential tape strips from 6 separate partings in the hair using clear Sellotape (5mm 3 80 mm). In 2 cases, tape sampling was stopped before reaching tapes 9 and10 because of safety considerations (eg, erythema at sampling site). The 5th and 6thsequential strips from the 6 partings were pooled as were the 9th and 10thsequential strips. The pooled tape strip samples (2 per subject) were analyzed forthe presence of d35-stearic acid using LC-MS. Two samples were damaged during theanalytic processing and therefore no data were available. A 1-sided binomial test wasused to test the null hypothesis that no deuterated stearic acid was present versusthe alternative hypothesis that deuterated stearic acid was present. A 5% level ofsignificance was employed.

Results: Females: d35-stearic acid was detected in 20 out of 20 tape 5 and 6 samplesand 18 out of 19 tape 9 and 10 samples. Males: d35-stearic acid was detected in 21out or 22 tape 5 and 6 samples and 20 out of 22 tape 9 and 10 samples. In all cases,the null hypothesis was rejected (P\.0001).

Conclusion: We have demonstrated that stearic acid does penetrate into scalpstratum corneum when delivered from fully formulated zinc pyrithione shampooformulations.

ded by Unilever PLC.

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P7016Dermatologic assessment of the skin tolerance of a daily shave with a 5-blade razor for men with sensitive skin

Pamela Zupkosky, Procter and Gamble, Boston, Massachusetts, MA United States;Kristina Vanoosthuyze, PhD, Procter and Gamble, Reading, United Kingdom

Background: Sensitive skin is a common problem among men and women. Themanagement and care of sensitive skin can be very difficult, both for the consumerand for the physician who is consulted about this. For men, this is furthercomplicated by the need for (sometimes daily) facial hair removal. The sensorysymptoms during and after shaving can be intense for men with sensitive skin andtypically include a feeling of burning, stinging, and itching. The quality of their shaveexperience depends on a myriad of factors, including their shaving technique andthe quality of their razor and grooming products.

Objective: To assess how a manual and a powered 5-bladed razor are tolerated bymen with self-assessed sensitive skin under conditions of a daily shave during a4-week period. The razors have been designed so that the blades pass over the skinand through the hair with minimal impact.

Methods: A 28-day study was conducted amongst 60 male volunteers with self-assessed sensitive skin and who were randomly assigned to 1 of 2 razors to yield afinal panel size of n¼ 30 for each razor. The facial and neck skin were examined andgraded by a dermatologist on day 1 (before the first shave) and on day 28 (after thelast shave). Gradingwas done on a 4-point scale (0¼ none; 1¼ slight; 2¼moderate;3 ¼ severe) for visual signs of erythema and dryness. The panelists graded theirsubjective symptoms of burning, stinging, itching, and soreness on a similar scaleand at the same time points.

Results: The dermatologist concluded that both razors were well tolerated and safeto use for men with sensitive skin, even when used to remove facial hair on a dailybasis. There were no adverse events reported and several attributes showedimprovements during the course of the study.

Conclusion: For the manual razor, there was a directional reduction for both visualgrades and for the sensory symptoms of stinging, itching, and soreness. Thesubjective score for burning decreased in a statistically significant way (P ¼ .015).For the powered razor, visual erythema decreased significantly (P ¼.003) and therewas a directional reduction in the dryness, burning, and itching scores. At the end ofthe study, the grades for dryness, stinging, burning, and itching were 0 for allpanellists.

hors are employees of Procter and Gamble.

Both aut

J AM ACAD DERMATOL AB35