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 tretinoinMeningkatkan kelembutan kulit dengan Mempengaruhi dermisSecara klinis untuk mereduksi kerutanUS tretinoin is drug bukan cosmeceutical, pharmaceuticalhowever study of the mechanisms of tretinoin action may lead to improved “cosmeceutical approaches” to anti-aging
11 RETINOIDSOlsen 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 Duration of treatment was 24 weeks. RETINOIDSSubjects 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
14 RETINOIDSTEC 0.05% secara signifikan berbeda dengan vehicle dalam mengurangi semua kerusakan akibat photo-damage mulai awal hingga akhir terapi
15 RETINOIDSPigmentasi belang-belang, kerutan and kulit kasar menurun dengan terapi TEC 0.05% dibanding vehicle.
16 RETINOIDSPeningkatan 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 hiperpigmentasiTerapi 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 22nd IFSCC conference, Edinburgh 2002
20 In a face study retinoic acid was clearly superior to AHA+Retinol Scott, proceedings of the 22nd IFSCC conference, Edinburgh 2002
21 Niacinamide Larut air menghasilkan turunan Vitamin B Ketika ditambahkan sunscreen dapat mencerahkan noda hitam pada kulitMemicu kelembutan permukaan kulitOlay total effectsL’Oreal PlentitudeMenghalangi transfer pigment granular dari sel tempat produksi pigment (melanocytes) ke keratinocytes.
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)
25 Niacinamide does not lighten human melanocytes in culture Greatens, Wickett and Boissy, unpublished data
26 Niacinamide inhibited melanosome transfer in vitro. 10 mM niacinamide after 6 daysGreatens et al Experimental Dermatol (2005)
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 placeboBissett 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. DermatolThe authors found the combination to be effective in reducing facial wrinkles.
30 Effects of Niacinamide and Kinetin on facial wrinkles
31 ANTIOXIDANTSPanahan radikal bebas atau bahan kimia yang mempercepat dalam menetralisir radikal bebasKulit target organ pada photo-oxidative lingkunganSpesies oksigen reaktif menghasilkan struktur dan fungsi pergantian kulit (i.e. breakdown of type III collagenPenggunaan antioksidan dapat mengurangi tosisitas photo-oxidative yang dipercaya merupakan strategi penting dalam mengatur photo-aging.
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 10% Ascorbic Acid, 7% tetrahexyldecyl ascorbateTreatment for 12 weeks, double blind split face.Fitzpatric and Rostan(2002) Dermatol Surg 28:
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 rq (root mean square roughness) with treatment Data replotted from Raschke et. Al. (2004) Vertical axis is reduction in rq 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 PeptidesRecently there has been considerable interest in the use of short peptide sequences as cosmeceutical activesPeptide 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 ResultsExpert 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 NAGGlucosamine and N-acetyl glucosamine are precursors of hyaluronic acid.These “sugar amines” have been investigated as both oral and topical ingredients for improving skin conditionBissett 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 skinStudies 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
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 treatmentSome will be up regulated some down regulatedHow do you decide what is a positive effect?Which genes are most important to a positive interpretation?