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Cosmeceuticals. “cosmetic” “pharmaceutical” a cosmetic product that exerts a pharmaceutical therapeutic benefit but not necessarily a biologic therapeutic.

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Presentasi berjudul: "Cosmeceuticals. “cosmetic” “pharmaceutical” a cosmetic product that exerts a pharmaceutical therapeutic benefit but not necessarily a biologic therapeutic."— Transcript presentasi:

1 Cosmeceuticals

2 “cosmetic” “pharmaceutical” a cosmetic product that exerts a pharmaceutical therapeutic benefit but not necessarily a biologic therapeutic benefit a cosmetic product that exerts a pharmaceutical therapeutic benefit but not necessarily a biologic therapeutic benefit

3 Mechanisms of current cosmeceutical agents. Alpha-hydroxyacid (AHA), post- inflammatory hyperpigmentation (PIH), ultraviolet light (UV). melanocytes keratinocytes fibroblasts

4 Some Cosmeceuticals Gau et. Al. (2008) Clinics in Dermatology

5 Some Cosmeceuticals Gau et. Al. (2008) Clinics in Dermatology

6 Anti-Inflammatory Agents Clinical trials evaluating cosmeceuticals agents

7 Anti-Inflammatory Agents

8 Role of cosmeceutical agents on wound healing

9 RETINOIDS “Gold Standard” against which all other for photo-aging could be compared. Sebagai metabolit retinol (Vitamin A) Diketahui semua berasal dari trans asam retinoat atau tretinoin Meningkatkan kelembutan kulit dengan Mempengaruhi dermis Secara klinis untuk mereduksi kerutan US tretinoin is drug  bukan cosmeceutical,  pharmaceutical however study of the mechanisms of tretinoin action may lead to improved “cosmeceutical approaches” to anti-aging

10 Retinol and metabolites

11 RETINOIDS Olsen et.al menunjukkan potensial sfektifitas pada krim topical tretinoin emollient (TEC) untuk menyembuhkan photo-damaged skin. 320 healthy, white persons with mild to moderate facial photo-damage were selected. Subjects were equally randomized into 4 treatment groups, – TEC 0.05%, – TEC 0.01%, – TEC 0.001% – Vehicle. –Olsen et al(1992) J. Amer. Acad. Dermatol 26:

12 RETINOIDS Subjects were instructed to apply the assigned test cream to the entire face. Duration of treatment was 24 weeks. 2mm punch biopsy specimens were obtained before therapy and after 24 weeks of treatment from adjacent areas. – Olsen et al(1992) J. Amer. Acad. Dermatol 26:

13 RETINOIDS (A) Pretreatment appearance (B) Appearance at week 24 of TEC (A) Pretreatment appearance (B) Appearance at week 24 of TEC

14 RETINOIDS TEC 0.05% secara signifikan berbeda dengan vehicle dalam mengurangi semua kerusakan akibat photo-damage mulai awal hingga akhir terapi

15 RETINOIDS Pigmentasi belang-belang, kerutan and kulit kasar menurun dengan terapi TEC 0.05% dibanding vehicle.

16 RETINOIDS Peningkatan ketebalan epidermis dan ketebalan lapisan granular. Melanin menurun 56% dengan TEC 0.05% dan 57% dengan TEC 0.01%.

17 Retinol a cosmetic anti-aging active or “cosmeceutical”

18 Effects of retinol and retinyl propionate on wrinkling and hyperpigmentation  Retinol (ROH) and retinyl propionate (RP) dapat menurunkan kerutan dan hiperpigmentasi  Terapi 4, 8, and 12 minggu  iritasi rendah oleh RP vs ROH menjadikan penggunaan pada tingkat yang lebih tinggi diijinkan. Bissett, Clinics in Dermatology (2009) 27, 435–445

19 Scott melaporkan bahwa retinol and AHA + retinol efektif menghilangkan kerusakan kulit lengan Scott, proceedings of the 22 nd IFSCC conference, Edinburgh 2002

20 In a face study retinoic acid was clearly superior to AHA+Retinol Scott, proceedings of the 22 nd IFSCC conference, Edinburgh 2002

21 Niacinamide Larut air menghasilkan turunan Vitamin B Ketika ditambahkan sunscreen dapat mencerahkan noda hitam pada kulit Memicu kelembutan permukaan kulit – Olay total effects – L’Oreal Plentitude Menghalangi transfer pigment granular dari sel tempat produksi pigment (melanocytes) ke keratinocytes.

22 Niacinamide (Nicotinamide)

23 5% Niacinamide reduced hyperpigmentation in human clinical trial Hakozaki et al. (2002) Brit. J. Derm

24 5% Niacinamide over 8 weeks of treatment Greatens et al Experimental Dermatol (2005) Week 0Week 8Week 4

25 Niacinamide does not lighten human melanocytes in culture Greatens, Wickett and Boissy, unpublished data

26 Niacinamide inhibited melanosome transfer in vitro. Greatens et al Experimental Dermatol (2005) 10 mM niacinamide after 6 days

27 The effect of niacinamide on pigmentation in vivo is reversible Greatens et al Experimental Dermatol (2005)

28 12 weeks of treatment with niacinamide reduced facial wrinkles measured by image analysis more than placebo Bissett et al (2004) Int. J. Cos. Sci

29 Kinetin Kinetin  Hormon pertumbuhan tanaman Mempunyai sifat “anti-aging” dan “anti-oxidant” pada sel. Chiu et. Al. reported on the effects of combining kinetin and niacinamide in a human clinical trial. – Chiu et. Al. (2007) J. Cosmet. Dermatol The authors found the combination to be effective in reducing facial wrinkles.

30 Effects of Niacinamide and Kinetin on facial wrinkles

31 ANTIOXIDANTS Panahan radikal bebas atau bahan kimia yang mempercepat dalam menetralisir radikal bebas Kulit  target organ pada photo-oxidative lingkungan Spesies oksigen reaktif menghasilkan struktur dan fungsi pergantian kulit (i.e. breakdown of type III collagen Penggunaan antioksidan dapat mengurangi tosisitas photo-oxidative yang dipercaya merupakan strategi penting dalam mengatur photo-aging.

32 Vitamin C

33 Topical vitamin C has been reported to improve photoaging Fitzpatric and Rostan(2002) Dermatol Surg 28:

34 Improvement in wrinkle scores C was significant over baseline but NOT over vehicle Fitzpatric and Rostan(2002) Dermatol Surg 28: % Ascorbic Acid, 7% tetrahexyldecyl ascorbate Treatment for 12 weeks, double blind split face.

35 Vitamin C and photoaging Raschke et. Al. reported that ascorbic acid in an oil-in-water emulsion was superior to its vehicle in a 12 week split face test. – Raschke et. Al. (2004) Skin Parmacol Physiol 17: The authors reported reduced oxidative stress in the skin and significant improvement in wrinkles (roughness values by PRIMOS) compared to vehicle

36 Decrease in r q (root mean square roughness) with treatment Data replotted from Raschke et. Al. (2004) Vertical axis is reduction in r q as measured by PRIMOS result at 12 weeks is statistically significant.

37 Lipoic acid 6-8 dithiooctanoic acid Reported to be effective for treating photoaging

38 Effect of 3 month treatment with 5% LA Beitner Brit. J. Dermatol (2003)

39 Laser profilometry indicated a significant improvement in wrinkles

40 Peptides Recently there has been considerable interest in the use of short peptide sequences as cosmeceutical actives Peptide sequences that can stimulate fibroblasts to produce collagen in-vitro are used. The most widely studied sequence is lysine-threonine- threonine-lysine-serine (KTTKS) found on type I procollagen. See Lupo and Cole (2007) Cosmeceutical Peptides Dermatologic Therapy 20: for a review.

41 Robinson et al reported that topical application of a palmitoyl derivative of KTTKS, PAL-KTTKS improved signs of photoaging. Robinson et. Al(2005) Int. J. Cosmet. Sci

42 Improvement of wrinkle grades by pal-KTTKS Robinson et. Al(2005) Int. J. Cosmet. Sci

43 Image analysis also showed directional improvement

44 Results Expert grading of photographs did show a significant effect versus placebo at 4 weeks (but not at 12) Subjects self assessment of “age spots” showed a significant advantage over placebo. The authors concluded that “Topical 3-ppm pal- KTTKS was shown to provide a reduction in facial lines/wrinkles in a 12 week clinical test”.

45 NAG Glucosamine and N-acetyl glucosamine are precursors of hyaluronic acid. These “sugar amines” have been investigated as both oral and topical ingredients for improving skin condition Bissett reports that 2% NAG applied topically has been found to have positive effects on both wrinkles and hyperpigmentation. Bissett, D. (Clinics in Dermatology (2009) 27, 435–445

46 NAG enhanced the ability of Niacinamide to reduce “age spots” Computer image analysis of Caucasian facial digital images for change in spot area fraction. More negative numbers indicate reduction in hyperpigmentation (improvement). N, niacinamide; NAG, N-acetyl glucosamine. P is for 4% N + 2% NAG vs 4% N. Bissett, D. (Clinics in Dermatology (2009) 27, 435–445

47 Gene expression and cosmeceutical research A recent trend in cosmeceutical research is investigate the effects of treatments on gene expression in the skin Studies are done either in-vitro with explants from surgery or organotypic skin cultures such as those from MatTek or in-vivo followed by biopsies. Either gene chips such as Affymetrix or rt-PCR techniques are used investigate treatment effects on gene expression

48 The Affymetrix gene chip

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53 Gene expression before and after UV exposure from microarray analysis Enk et. Al. Photodermatol Photoimmunol Photomed 2004; 20: 129–137

54 Verification of specific genes by rt-PCR

55 Challenges with genetic analysis and cosmeceutical research Dozens or even hundreds or perhaps thousands of genes may be changed over the course of a treatment Some will be up regulated some down regulated How do you decide what is a positive effect? Which genes are most important to a positive interpretation?


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