DermaPep A530. Multifunctional anti-inflammatory peptide for irritated and sensitive skin. Experience The Magic of Science

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Experience The Magic of Science DermaPep A53 Multifunctional anti-inflammatory peptide for irritated and sensitive skin DermaP ep Experience the magic of science

Anti-aging DermaPep A35 DermaPep A42 DermaPep A44 DermaPep A53 DermaPep WrinCare Whitening DermaPep A35 DermaPep UL DermaPep W22 DermaPep W411 Anti-inflammatory DermaPep A35 DermaPep A44 DermaPep A53 DermaPep WrinCare DermaPep UL DermaPep W22 DermaPep W411 Hair Growth and Anti-Hair Loss DermaPep Pepanagen

DermaPep A53 Multifunctional anti-inflammatory peptide for irritated and sensitive skin Introduction Sensitive skin represents a widespread condition of susceptibility to exogenous factors. Sensitive skin is often defined by a propensity to sensory responses such as stinging, itching, burning or visible reactions, such as erythema, papules or vesicles, wheal and flare responses, dryness, scaling and desquamation, in response to external stimuli. It is hypothesized that various conditions induce the symptoms of sensitive skin, such as environmental factors (pollution), physical factors (UV, heat, cold), psychological factors (stress, emotion) or hormonal factors (menstrual cycle). Recent studies indicate that well over half of the population consider themselves to have sensitive skin, with about one third perceiving that their skin is getting more sensitive. Although there is widespread nature of sensitive skin, a single definition of this condition remains elusive. Two primary reasons may be responsible for the symptoms occurring in sensitive skin; an increased permeability of the stratum corneum (low barrier function) or an acceleration of nerve responses (inflammatory changes). A thinner stratum corneum causes a higher transcutaneous penetration which makes more susceptible to chemical irritation. Impaired skin barrier function, together with an increase in transepidermal water loss (TEWL) has been hypothesized to underline skin sensitivity. In addition, neurosensory dysfunction of nerves in the skin underlies the altered sensations. The sensory receptors are not only expressed on nerve endings, but also in keratinocytes, which may explain why sensitive skin responds to different environmental, physical and chemical factors limited to the skin. Function Inhibition of inflammation pathway Providing exceptional anti-inflammation benefits Anti-inflammation effect against environmental stimulus such as UV irradiation Prevention of skin irritation and sensation Reducing itching and pruritus Applications DermaPep A53 can be incorporated in cosmetic formulations such as emulsions, oily sera, gels and creams for anti-inflammatory and anti-aging purpose. Formulation Dermatological tolerance : Standard testing has been performed on DermaPep A53 which has showed neither cytotoxic effects nor any irritation or sensitization reaction in healthy volunteers with an occlusive single patch test. Recommended concentration : 2-4 % Product Information Appearance : Transparent Solution INCI/CTFA-Declaration : Capryloyl Pentapeptide-26 (and) Propylene Glycol Active ingredient content :.5 % Capryloyl Pentapeptide-26 Powder purity : 95 % up Preservative : None Capryloyl pentapeptide-26 represents the most effective active ingredient for irritated and sensitive skin. It greatly reduced inflammatory cytokine expressions and productions in vitro, especially IL-1α, IL-8 and TNF-α, three most important cytokines that have been known to cause skin irritation. Capryloyl pentapeptide-26 also clinically proved to reduce skin inflammation and irritation.

Cell viability (% of control) DermaPep A53 Safety Cell Cytotoxicity Test Human keratinocytes HaCaT cells were seeded into 96- well plates (2 x 1 3 ) and treated with different concentrations of Capryloyl pentapeptide-26 for 48 hours. Cell viability was assessed by MTT assay and was shown relative to untreated control. Absorbance was measured by an ELISA reader at 54 nm. Skin Irritation Test Skin irritation test was performed on 31 healthy Asian volunteers (Spincontrol Asia (study report number IR- 6Q1-MW-DE8), Bangkok, Thailand). Evaluation and grading of skin irritation Erythema (no redness = to very strong redness = 5) After 24 hrs, mean score =. (max = ) After 48 hrs, mean score =. (max = ) Oedema (no oedema = to very strong oedema = 5) After 24 hrs, mean score =. (max = ) After 48 hrs, mean score =. (max = ) Scaling (no scaling = to very strong scaling = 5) After 24 hrs, mean score =. (max = ) After 48 hrs, mean score =. (max = ) In vitro Ocular Irritation Test DermaPep A53 at 3 different concentrations (2, 4, 8 %) and butylene glycol with glycerin were evaluated with the ocular irritection assay system (CA, USA). MTT Assay The ocular results demonstrated that the DermaPep TM A53 was classified as mild irritants. 14 12 1 8 6 1 115 114 111 77 58 4 2 1 5 1 5 1 5 Concentration (ppm) 5

Cytokines Contents (% of control) DermaPep A53 In vitro efficacy Inhibition of UV-induced Pro-inflammatory Cytokines Expression HaCaT cells were exposed to UVB (75 mj/cm 2 ) and treated with various concentrations of Capryloyl pentapeptide-26 (1, 1, 2 ppm) for 24 hours. Equal amounts of media were analyzed by ELISA assay for IL-1α, IL-1β, IL-6, IL-8. Cell viability was used for sample standardization. Total cellular RNA was extracted and reverse transcription PCR was performed to determine IL-1α, IL-1β, IL-6, IL-8, PGE2, TNFα, Cox-2 and GAPDH. GAPDH mrna level was used for sample standardization Capryloyl pentapeptide-26 considerably inhibited both the production of IL-1α, IL-1β, IL-6, IL-8 and the expression of IL-1α, IL-1β, IL-6, IL-8, PGE2, TNFα, Cox-2 mrna induced by UVB. By reducing Proinflammatory cytokines, Capryloyl pentapeptide-26 showed powerful anti-inflammatory effect. Inhibition of UVB-Induced Pro-inflammatory Cytokines Expression and Production UVB 75mJ/cm 2 12 1 15 929 Cap-Pentapeptide-26 NT 1 1 (ppm) IL-1 8 6 4 2 1 717 62 697 526 472 347 293 274 244 242 181 167 153 123 UVB 75mJ/cm 2 + + + + Capryloyl Pentapeptide-26 5 1 2 (ppm) IL-1α IL-1β IL-6 IL-8 IL-1β IL-6 IL-8 PGE2 TNF Cox-2 GAPDH

Cytokines Contents (% of control) DermaPep A53 In vitro efficacy Inhibition of SP-induced Pro-inflammatory Cytokines Expression HaCaT cells were stimulated by substance P(5nM) and treated with various concentrations of Capryloyl pentapeptide-26 (1, 1ppm) for 24 hours. Equal amounts of media were analyzed by ELISA assay for IL-8, TNFα. Cell viability was used for sample standardization. Total cellular RNA was extracted and reverse transcription PCR was performed to determine IL-1α, IL-8 and GAPDH. GAPDH mrna level was used for sample standardization Capryloyl pentapeptide-26 significantly reduced both the production of TNFα, IL-8 and the expression of IL-1α, IL-8 mrna induced by Substance P. Inhibition of SP-Induced ILs and TNFα Cytokines Expression and Production 3 279 25 236 Substance P 5nM 2 15 1 5 1 169165 135 124 IL-8 TNF-α Cap-Pentapeptide-26 NT 1 1 (ppm) IL-1 IL-8 GAPDH -73% -138 % SP(5nM) + + Capryloyl Pentapeptide-26 1 + 1 (ppm)

Cytokines Contents (% of control) DermaPep A53 In vitro efficacy Inhibition of TNFα-induced Interleukine Cytokines Production HaCaT cells were stimulated by TNFα and treated with various concentrations of Capryloyl pentapeptide-26 (1, 1, 2 ppm) for 24 hours. Equal amounts of media were analyzed by ELISA assay for IL-1α, IL-1β, IL-6, IL-8. Cell viability was used for sample standardization. Capryloyl pentapeptide-26 effectively reduced the production of IL-1α, IL-1β, IL-6, IL-8 induced by TNFα. Inhibition of TNFα-Induced Interleukines Production 7 6 5 4 3 2 1 1 579 546 511 471 45 476 438 41 43 364 41 32 282 235 225 196 TNFα(1ng/ml) + + + + Capryloyl Pentapeptide-26 5 1 2 (ppm) IL-1α IL-1β IL-6 IL-8

DermaPep A53 In vitro efficacy Effects on Sebocyte Human sebocyte cells were stimulated by substance P(5nM) and treated with Capryloyl pentapeptide-26 (6,757, 13,514 nm) or dexamethasone or spantide 1 for 24 hours. Total cellular RNA was extracted and reverse transcription PCR was performed to determine IL-, β,6,8, Filaggrin, Loricrin, PPARγ and GAPDH. GAPDH mrna level was used for sample standardization. Capryloyl Pentapeptide-26 are effective on reducing inflammatory cytokines in sebocyte. Effects on Sebocyte SP 5nM Dex Spantide I Cap-Pentapep-26 2 5 2 5 6757 13514 (nm) IL-1a IL-1b IL-6 IL-8 Filaggrin Loricrin PPARγ GAPDH * Dex : Dexamethasone Spantide I : NK1R-specific antagonist

Average inflammation score DermaPep A53 In vivo clinical efficacy Anti-Inflammatory Efficacy In a clinical study conducted on 32 healthy Asian female volunteers, aged 29 t 6, a local inflammation was created on the inner arm by the application of patch containing sodium lauryl sulfate (SLS) with or without a cream containing 1ppm of Capryloyl Pentapeptide-26 Dermatological evaluation (erythema, oedema and scaling), chromametry and trans-epidermal water loss were used to measure the skin inflammatory reaction. Clinical test schedule Reduction of Global Inflammation Score Evolution of The Global Inflammation Score.6.5.4.3.2.1. T+24 hours T+48 hours T+3 days* T+1 week* 15% SLS 15% SLS + 4% DermaPep A53 (Time) Highest global inflammation score was obtained at 24 hours after the application of SLS and DermaPep A53 showed excellent preventive effects not only at 24 hours but also at all the time points measured. Dermatological evaluation was demonstrated by the significant reduction of the global inflammation score (combining erythema, oedema and scaling) compared to the skin treated with SLS only. Erythema = No redness, 1 = Weak redness, 2 = Moderate redness, 3 = Strong redness, 4 = Very strong redness Oedema = No oedema, 1 = Weak oedema, 2 = Moderate oedema, 3 = Strong oedema, 4 = Very strong oedema Scaling = No scaling, 1 = Weak scaling, 2 = Moderate scaling, 3 = Strong scaling, 4 = Very strong scaling

T.E.W.L. values Chromaticity a* DermaPep A53 In vivo clinical efficacy Reduction of Skin Redness DermaPep A53 significantly decreased the skin redness. Skin redness was determined by measuring the parameter a* in the L* a* b* color system using a chromameter. a* characterizes the color intensity from green to red and an increase of a*indicates an increase of the red constituent of the skin. Evolution of The Chromaticity a* (Cutaneous Redness) 11.5 11. 1.5 1. 9.5 9. 8.5 8. 7.5 7. 6.5 T T+24 hrs T+48 hrs T+3 days* T+1 week* 15% SLS 15% SLS + 4% DermaPep A53 (Time) Reduction of Trans-Epidermal Water Loss (TEWL) TEWL is one the most important parameters to evaluate the epidermal permeability barrier function of the skin. A low TEWL is generally a characteristic feature of an intact skin function. Thus, irritating agents compromising the skin barrier increase transepidermal evaporation. A Maximum TEWL value was obtained at 24 hours after the treatment of SLS and DermaPep A53 greatly reduced the Trans-Epidermal Water Loss (TEWL). Evolution of Trans-epidermal Water Loss (TEWL) (Barrier Function of The Skin) 8 7 6 5 4 3 2 1 T T+24 hrs T+48 hrs T+3 days*t+1 week* (Time) 15% SLS 15% SLS + 4% DermaPep A53

DermaPep A53 Multi-functional peptide for anti-itching In Vivo Anti-Itching Efficacy The clinical test was performed on 16 volunteers (Korea), aged 24 to 56, who have severe dry and sensitive skin including pathological skin conditions such as atopic or contact dermatitis. 1ppm of Capryloyl Pentapeptide-26 has been applied once daily in the evening for 28 days. DermaPep A53 was proved to greatly suppress the itching sensation and to provide excellent soothing and calming effects. 1. Would you say the product has reduced itching? Completely suppressed 13 Moderately suppressed 3 No difference Worsened 2 4 6 8 1 12 14 16 [volunteers] 2. How do you judge soothing and calming effect? Excellent Good No difference Poor Bad 4 12 2 4 6 8 1 12 14 16 [volunteers]

Personal Care Ingredients Business Unit http://www.dermapep.com E-mail : dermapep@mwc.co.kr Last revised on Oct 2 th, 214 MIWON COMMERCIAL CO., LTD. 45-3 MONGRAE-DONG, DANWON-GU, ANSAN-SHI, GYEONGGI, 425-1, KOREA PHONE +82-31-884-841 FAX +82-31-492-261 www.dermapep.com, www.mwc.com