Synopsis 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.
The objective of this in vivo pilot study was to investigate whether differential biomarker analysis from skin tape strips could be used, not only to evaluate the difference between treated and untreated skin, but also to evaluate the effect of different product treatments. Ten volunteers were included in the study, applying two different basic formulations on their forearms. After four weeks of product application, and also after one week of treatment remission, tape strips were collected from the different treatment sites, as well as from untreated skin. The biomarkers investigated were selected to cover different aspects of epidermal differentiation and in connection with moisturization and barrier function. Levels of Involucrin were increased in both treatments, compared to untreated skin, whereas the levels of Keratin-6 were decreased for both treatments. In addition, a pattern for increased levels of Hornerin and Claudin-1 was also detected. There were no significant differences between the two treatments, only for treatment compared to untreated, but there were tendencies for different effect on some of the biomarkers investigated, differences that may reach significance with increased sample size. The major differences between the two treatments in this study were seen after one week of product remission, although due to too small sample size these differences were not significant.
Synopsis Background Acetyl aspartic acid (A‐A‐A) was discovered through gene array analysis with corresponding connectivity mapping (Cmap). Using an in silico and in vitro approach, A‐A‐A was found increased keratinocyte regeneration, inhibited dermal expression of MMP making this compound a potential active ingredient for cosmetic application. Objectives To determine the conditions to successfully formulate A‐A‐A for skin delivery investigation and in vivo clinical assessment by the systematic approach of pre‐formulation testing of the active, screening of formulation type on active delivery and stability evaluations. Methods Analytical evaluation of A‐A‐A was undertaken using LC‐MS ESI method. Formulation stability was evaluated using Brookfield viscometer, pH analysis, optical microscopy and organoleptic evaluations. Results Analytical evaluation of A‐A‐A shows that pH significantly impacts chemical stability of the molecule. A‐A‐A containing formulae show minimal differences to vehicle product throughout the testing. Conclusion A‐A‐A is an active that can be successfully formulated in a cosmetic o/w emulsion within defined pH considerations.
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