REVINAGE. The real bio-retinol
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1 REVINAGE The real bio-retinol
2 Aging of the world United Nations 2015 Report
3 Aging Who wants to get old?
4 Retinoids o Family of compounds related to vitamin A and its derivatives o They interact with specific nuclear receptors RAR (retinoic acid receptors) and RXR (retinoid X receptors) o Retinoic acid is the most active and reactive form (with side effects). Retinol and its esters are converted into retinoic acid to provide biological function.
5 Retinoids o Highly efficient for the treatment of aging, photoaging, acne, psoriasis and others o The most prescribed active ingredient o Diverse side effects include: skin irritation, photosensibility, telangiectasia, teratogenicity and embriotoxicity o Instability in contact with light and oxygen
6 Retinol-like activity Vegetal alternative to retinoids in the treatment of aging and photoaged skin. Supercritical apolar extract of Picão Preto (Bidens pilosa) standardized in phytol INCI: Bidens Pilosa Extract (and) Elaeis Guineensis (Palm) Oil (and) Gossypium Herbaceum (Cotton) Seed Oil (and) Linum Usitatissimum (Linseed) Seed Oil.
7 Retinoids Receptors In silico evaluation of RXR and phytanic acid RXR (retinoid X receptors) Hydrogen bounds (yellow traces) between the oxygen atoms of phytanic acid (in red) and arginine R316 (in RXR receptor)
8 Gene expression (mrna) Retinoids Receptors Human fibroblasts culture 48hs gene expression of RAR and RXR receptors 2,5 2 62,3% 90% 119% 1,5 34% 1-26% -20% 0,5 0 RAR RXR Control Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) RAR (retinoic acid receptors) and RXR (retinoid X receptors)
9 Retinoids Receptors Ex vivo 48hs protein expression of RAR and RXR RAR RXR RAR (retinoic acid receptors) and RXR (retinoid X receptors)
10 Gene expression (mrna) Cellular proliferation, differentiation and extracellular matrix (ECM) Human fibroblasts culture 48hs gene expression 3 2,5 2 1,5 1 0, % 120% 134% 108% 121% 67% EGFr Pro-collagen Controle Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) EGFr epidermal growth factor receptor
11 Protein level (mg/ml) Cellular proliferation, differentiation and extracellular matrix (ECM) Human fibroblasts culture 48hs protein expression % 46% 24% collagen 67% 17% elastin 26% Control Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) p<0,05 in relation to the control
12 Cellular proliferation, differentiation and extracellular matrix (ECM) Skin fragments 24hs protein expression
13 MMP-1 production (% in relation to the control) Cellular proliferation, differentiation and extracellular matrix (ECM) Human fibroblasts culture 48hs protein expression Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) MMP-1 metalloproteinase type I
14 MMP-1 (pg/ml) Cellular proliferation, differentiation and extracellular matrix (ECM) Skin fragments 24hs protein expression % -14% -22% -7% Basal UV Placebo Retinol palmitate (2%) Revinage (2%) UV radiation (3J/cm 2 ) p<0,05 in relation to the control MMP-1 metalloproteinase type I
15 FGF- (pg/ml) Cellular proliferation, differentiation and extracellular matrix (ECM) Human fibroblasts culture 48hs protein expression % 71% 138% Control Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) p<0,05 in relation to the control FGF- - fibroblast growth factor
16 TGF- (pg/ml) Cellular proliferation, differentiation and extracellular matrix (ECM) Human fibroblasts culture 48hs protein expression % 26% 41% Control Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) p<0,05 in relation to the control TGF- - tissue growth factor
17 SOD activity (U/mL) Antioxidant and regulation of senescence Human fibroblasts culture 48hs enzymatic activity 1 445% 0,8 0,6 0,4 219% 247% 99% 0,2 0 Control Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) Alfa-tocopherol (0,15%) p<0,05 in relation to the control SOD superoxide dismutase
18 CAT Activity (U/mL) Antioxidant and regulation of senescence Human fibroblasts culture 48hs enzymatic activity % 67% 47% 60% Control Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) Alfa-tocopherol (0,15%) p<0,05 in relation to the control CAT catalase
19 Free radicals quantification (relative to light units RUL/min) Antioxidant and regulation of senescence Mouse fibroblasts culture 48hs free radicals quantification % Control Revinage (0,15%)
20 MDA (mm) Antioxidant and regulation of senescence Human fibroblasts culture 48hs MDA quantification % -41% -30% -90% Control Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) Alfa-tocopherol (0,15%) p<0,05 in relation to the control MDA malonaldelhyde
21 SIRT6 gene expression (mrna) Antioxidant and regulation of senescence Human fibroblasts culture 48hs gene expression 2 70% 70% 72% 1,5 1 0,5 0 Control Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) SIRT6 sirtuin 6
22 AP-1 activity (% in relation to the control) Soothing effect Human fibroblasts culture 48hs enzymatic activity Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) AP-1 activator protein-1 (transcriptional factor)
23 COX-2 (ng/ml) PGE2 (pg/ml) Soothing effect Human keratinocytes culture 48hs protein expression 2,5 2 1,5 1 8,5% -33% # -69% % # -5% # -26% 0, Control Retinoic Acid (30 µm) 0 Control Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) Retinol (0,15%) Revinage (0,15%) p<0,01 and # p<0,05 in relation to the control COX-2 - Ciclo-oxigenase-2 PGE2 Prostaglandin 2
24 LTB4 (pg/ml) Soothing effect Human keratinocytes culture 48hs protein expression ,5% -16% -28% # Control Retinoic Acid (30 µm) Retinol (0,15%) Revinage (0,15%) # p<0,05 in relation to the control LTB4 Leukotriene B4
25 DHT (pg/ml) Oiliness Control Human keratinocytes culture 48hs protein expression % # 60-63% -64% # 30 0 Control Sebonormine (0,05%) Saw Palmeto (0,05%) Revinage (0,15%) p<0,01 and # p<0,05 in relation to the control DHT - di-hydro testosterone
26 alfa-msh (mg/ml) Whitening Effect Human melanocyte and keratinocyte culture 48hs Melanin Level (mg/ml) % # -50% 0,100 0,080 0,060 0,040 0,020 # -56% 0,000-26% # -23% # -72% Control alfa- arbutin 0,005% kojic acid 0,05% Revinage (0,15%) Control alfa- arbutin 0,005% kojic acid 0,05% Revinage (0,15%) p<0,01 and # p<0,05 in relation to the control Alfa-MSH - α-melanocyte-stimulating hormone
27 Clinical Study Panel 40 volunteers (phototype II, III e IV) Facial cream with 2% Revinage or 0.3% Retinol palmitate 2x a day for 56 days on the face (hemi-face) and forearm
28 % of improvement on elasticity (R2) Clinical Study Elasticity (R2) 40 volunteers Revinage 2% Retinol Palmitate 0.3% 2X a day for 56 days Face (hemi-face) 25% 20% 15% 10% 5% 0% 20% 18% 17% 17% 13% 10% 6% 0% D14 D28 D42 D56 Revinage Retinol Palmitate Cutometer
29 % of improvement on cutaneous density (arbitrary units of ultrasound) Clinical Study Re-densification 40 volunteers Revinage 2% Retinol Palmitate 0.3% 2X a day for 56 days Face (hemi-face) and forearm 35% 30% 25% 20% 15% 10% 5% 0% 30% 25% 25% 23% 16% 14% 14% 12% D42 D56 D42 D56 forearm face Revinage Retinol plamitate Ultrasound DUB - USB
30 % of dark spots compared to the basal (VISIA) Clinical Study Whitening (VISIA) 40 volunteers Revinage 2% Retinol Palmitate 0.3% 2X a day for 56 days Face (hemi-face) 0% D14 D28 D42 D56-20% -21% -40% -32% -36% -37% -60% -48% -53% -80% -100% -67% -86% Revinage Retinol Palmitate VISIA
31 % roughness (PRIMOS - Sa) Clinical Study Roughness and texture (Sa PRIMOS) 40 volunteers Revinage 2% Retinol Palmitate 0.3% 2X a day for 56 days Face (hemi-face) and forearm 0% -5% -10% -15% -20% -25% -30% -35% -40% forearm face D14 D28 D42 D56 D14 D28 D42 D56-11% -16% -16% -24% -23% -23% -23% -27% -26% -26% -29% -32% -37% -35% -36% -36% Revinage Retinol Palmitate PRIMOS
32 % wrinkles (PRIMOS - Smax) Clinical Study Wrinkles (Smax PRIMOS) 40 volunteers Revinage 2% Retinol Palmitate 0.3% 2X a day for 56 days Face (hemi-face) and forearm 0% -5% -10% -15% -20% -25% -30% forearm D42 D56 D42 D56-8% -10% -16% -15% -18% -18% -26% -28% Revinage Retinol Palmitate face PRIMOS
33 Clinical Study Wrinkles (Smax PRIMOS) Results after 28 days D0 D28 PRIMOS
34 Clinical Study Wrinkles (OMNIA) D zero D28 OMNIA
35 Clinical Study NMF and Lipids (Raman) 5 volunteers Revinage 1% at lipstick 1 single application Description 2hs 4hs NMF 92.78% - Ceramide-3 33% 55.86% Cholesterol % Raman Spectroscopy
36 Clinical Study Permeation (Raman) 2 volunteers Revinage 3% Placebo 1 single application Samples % of permeation of the active ingredient at 1-60µm (related to the phytol concentration) 30min 1h 2h 4h 18h 24h Placebo 0% 0% 0% 0% 0% 0% Cream with 8.12% 29.3% 62.17% 65.15% 9.13% 2.21% Raman Spectroscopy
37 % degradation Other Tests Degradation and Stability photodegradation (6 hs. under UV radiation in a sun simulator chamber) oxidation (peroxide at 3% for 15 hs. at 30 C) 0% -20% -40% -60% -80% -100% -120% photodegradation -3% -54% Retinol Oxidative degradation -8% -100% Revinage HPLC -High performance liquid chromatography
38 Benefits Provides "retinol-like" behavior by binding to the RXR receptor and reducing by 20% the RAR expression while increasing the RXR expression by 119% resulting in effective anti-aging and anti-photoaging action Regulates cell proliferation and differentiation as well as stimulates the production of extracellular matrix by ensuring greater skin firmness and wrinkles filling Offers antioxidant activity and senescence regulation
39 Benefits Provides a soothing effect Controls skin oiliness Offers a skin lightening effect Controls skin barrier Reaches the deepest layers of the skin in 4 hours High stability to photodegradation and oxidation
40 Benefits increases by 17% the elasticity of the facial skin of volunteers after 56 days increases by 25% the re-densification of the dermis in the face after 42 days reduce in 67% the hyperpigmented regions in the face after 56 days reduces the roughness of the facial skin in 36% after after 42 days reduces in 28% the deep wrinkles of the facial skin after 42 days
41 Application Cream, lotion, non-transparent gel, gel-cream, serum and oil for the treatment of aged and photo aged skin.. Not applicable to hydro alcoholic formulation. Stability and compatibility Add at the oil phase up to 85ºC ph: Suggested Concentration 1-3%
42 THANK YOU!
43
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