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Gillbro J.M.,Oriflame Skin Research Institute | Merinville E.,Oriflame RandD Ltd | Olsson M.,ParkCell AB | Al-Bader T.,Oriflame Skin Research Institute | And 3 more authors.
International Journal of Cosmetic Science | Year: 2015

Objective The need for effective 'anti-ageing' treatments, in particular for the management of photodamaged skin, prompted us to develop a novel method to identify new active ingredients. The model utilized a gene profiling study with corresponding connectivity mapping (Cmap) to identify novel anti-ageing compounds using all-trans retinoic acid (RA) as the lead compound due to its beneficial effect on photodamaged skin and skin firmness. Method A vehicle-controlled clinical study including nine healthy Caucasian female volunteers aged 57 ± 7 (mean ± SEM) exhibiting photodamage on their lower outer forearms was conducted. The volunteers applied RA once daily on photodamaged skin for 7 days, and biopsies were subjected to Affymetrix gene arrays. Connectivity mapping (Cmap), examining hundreds of gene expression profiles, was run on the gene signature of RA-treated photodamaged skin to identify small bioactive compounds. Results Affymetrix gene array identified 19 genes significantly differentially expressed after application of RA. Corresponding Cmap analysis revealed six natural bioactive compounds including N-acetyl aspartic acid (A-A-A) showing similar activity to RA on the differentially expressed genes identified. Conclusion Based on RA mimicking gene array activity, potential use within skincare on molecular size, safety assessment and sourcing, we identified the natural amino acid, A-A-A as a potential candidate to treat ageing skin. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie. Source


Merinville E.,Oriflame Skin Research Institute AB | Byrne A.J.,Oriflame RandD Ltd | Visdal-Johnsen L.,Oriflame Skin Research Institute AB | Bouvry G.,Oriflame Research and Development Ltd | And 3 more authors.
International Journal of Cosmetic Science | Year: 2012

Synopsis The aim of this work was to investigate the effects of 1,18-octadecen-9-dioic acid (dioic acid) and a Rumex occidentalis extract complex for their skin-lightening action in an Indian population. Prior to the clinical study, the efficacy of dioic as an inhibitor of melanogenesis was confirmed on dark-pigmented human melanocytes. As part of a 12-week vehicle-controlled clinical study, the skin-lightening effect of a test product containing 1% dioic acid, 2% of a Rumex occidentalis extract and sunscreens (SPF 15) was assessed on the facial skin of 71 Indian female volunteers. Change in skin colour was monitored by (A) Chroma Meter® measurement (L*, a*, b*) and Individual Typology Angle (ITA°) calculation and (B) Visual grading of standardized photographs by a dermatologist. Colorimetric measurements on volunteers' cheeks showed a significant increase of L* and ITA° compared to baseline after 4, 8 and 12 weeks of test product application. For both L* and ITA° measurements, changes were significantly different than the SPF 15-containing vehicle at weeks 4 and 12. These results were confirmed by the dermatological visual grading. The overall skin-lightening action of the test product was beyond the one observed with the SPF 15 vehicle. These findings show that a dioic acid and Rumex occidentalis complex deliver a significant skin-lightening effect on facial skin in an Indian population. © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie. Source


Gillbro J.M.,Oriflame Skin Research Institute | Merinville E.,Oriflame RandD Ltd | Cattley K.,Oriflame RandD Ltd | Al-Bader T.,Oriflame Skin Research Institute | And 3 more authors.
International Journal of Cosmetic Science | Year: 2015

Objective Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A-A-A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F-actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in-use trial demonstrated that 1% A-A-A was well tolerated. In this study, the aim was to investigate whether A-A-A could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study. Method Two separate double-blind vehicle-controlled in vivo studies were conducted using a 1% A-A-A containing oil-in-water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12-day treatment of A-A-A on collagen IV (COLIV) and fibrillin-1. In a subsequent pilot study, 0.1% retinol was used for comparison to A-A-A (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness. Results Twelve-day topical application of 1% A-A-A significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% A-A-A and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and A-A-A. However, only A-A-A exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of A-A-A as a skin-firming active ingredient. Conclusion In this study, we showed the in vivo efficacy of 1% A-A-A both on a protein level (fibrillin and collagen IV) and on a clinical end point, specifically skin firmness, providing proof that, acetyl aspartic acid has a strong potential as an anti-ageing 'cosmeceutical' ingredient answering the needs of our key consumer base. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie. Source


Daly P.,Oriflame RandD Ltd | Moran G.,Oriflame RandD Ltd
International Journal of Cosmetic Science | Year: 2015

Objective Acetyl aspartic acid (A-A-A) was proposed as a new novel active ingredient for use in cosmetics. The safety of A-A-A was assessed by following an in-house-developed 'New Ingredient Testing Strategy', which was designed in accordance with the Scientific Committee on Consumer Safety (SCCS) notes of guidance and the requirements of Annex I of the EU Cosmetics Regulation. The aim of the project was to determine whether A-A-A was safe for use in cosmetics and to determine a maximum permitted safe level in the formulations. Methods A literature review was conducted, consulting over 40 different information sources. This highlighted a number of gaps which required testing data. A-A-A was tested for phototoxicity according to OECD test guideline 432, skin irritation according to OECD test guideline 439 and eye irritation according to OECD test guideline 437. Dermal absorption of A-A-A was measured according to OECD test guideline 428 and was used to calculate the margin of safety (MoS). Finally, A-A-A was tested in a human repeat insult patch test (HRIPT) and a 14-day in-use tolerance study. Results A-A-A was non-phototoxic and was non-irritating to skin and eyes in in vitro testing. Dermal absorption was calculated to be 5%. The MoS for A-A-A was 351, at a level of 5%, for all cosmetic product types, indicating no systemic safety toxicity concern. A-A-A at 5% under occlusive patch on a panel of 50 adult volunteers induced no skin irritation or allergic reaction in the HRIPT study. Finally, repeated application of A-A-A to the periocular area, twice per day for 14 days, in 21 female volunteers, demonstrated that 1% A-A-A was well tolerated following dermatological and ophthalmological assessment in a cosmetic formulation. Conclusion A-A-A was assessed as safe by the cosmetic safety assessor for use in cosmetics at a level of 5% in all cosmetic product types, in line with the requirements of the EU Cosmetics Regulation and in accordance with the SCCS notes of guidance. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie. Source


Byrne A.J.,Oriflame RandD Ltd | Al-Bader T.,Oriflame Skin Research Institute AB | Kerrigan D.,Oriflame RandD Ltd | Hickey S.,Oriflame RandD Ltd | And 2 more authors.
Journal of Cosmetic Dermatology | Year: 2010

Basement membranes are thin structures present in the extracellular matrix that provide a supporting framework on which epithelial and endothelial cells reside. Type IV collagen is present ubiquitously in all basement membranes and plays an important role in cell adhesion, migration differentiation, and growth. These are especially important at the dermoepidermal junction (DEJ) in skin. A reduction in the levels of DEJ proteins occurs in photodamaged skin and especially Type IV collagen at the base of a wrinkle. In these studies, the ability of a triple peptide complex (TPC) to stimulate the production of collagen IV in human skin fibroblasts and its effects on photoaged skin was investigated. Fibroblasts, matured to represent " aged" cells, were stimulated for 72 h with the TPC as well as the three individual peptides constituting the complex, and collagen IV production by the fibroblasts was determined immunochemically. The results show that stimulation with the individual peptides at doses found in 1% (v/v) of the TPC did not result in soluble collagen IV production above levels detected by the non-stimulated cells. However, after stimulation with 1% (v/v) of the TPC, collagen IV was produced by the cells (1.4 ng/ng total protein ± 0.4 SD, n = 5) when compared to control un-stimulated cells (0.32 ng/ng total protein ± 0.1 SD, n = 5). This indicates that the combination of the individual peptides is necessary to synergistically stimulate collagen IV production. These findings suggest that the TPC could play a role in the strengthening of the DEJ through its ability to produce collagen IV. In order to determine whether these results translated into significant effects in vivo, we performed two studies. In the first four-week study, a double blind, placebo-controlled and fully randomized clinical study on 22 healthy Caucasian volunteers displaying moderate periorbital wrinkles, a significant reduction in wrinkle parameters determined by profilometry was observed over the 4-week period in comparison to the placebo. This result was reproduced in a 12-week monadic study which also showed improvements in expertly graded wrinkle scores. Collectively, these results effectively demonstrate the anti-aging applications of the TPC. © 2010 Wiley Periodicals, Inc. Source

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