Skin Filling and Firming Activity of a Hyaluronic Acid Inducing Synthetic Tripeptide

Abstract

Aging of skin manifests in loss of volume and firming due to degradation of extracellular matrix components such as collagen and hyaluronic acid leading to wrinkling and sagging. To counteract loss of facial volume and regain firmness, fillers like hyaluronic acid (HA) are commonplace in cosmetic dermatology. We developed a synthetic tripeptide tetradecyl aminobutyroylvalylaminobutyric acid urea trifluoroacetate with proven hyaluronic acid stimulating activity in vitro. This study investigated the filling and firming activity of the tripeptide. In vitro: Microtissue technology was used to construct spherical 3D-skin equivalents. These were exposed to a tripeptide solution and content of hyaluronic acid and its receptor CD44 were assessed using histological techniques. Skin tissue culture was used to assess HA expression ex vivo. A placebo controlled, randomized, in parallel groups study to assess the firming, filling, and moisturizing activity of the peptide product was designed. We recruited 30 female Caucasian volunteers age 40 to 60 per group. Product application was twice daily for 29 days. Skin volume, deformation and moisturization were measured. HA and CD44 content in skin were increased in vitro and ex vivo. In vivo, skin firming was improved by a significant decrease in cheek deformation, a significantly restored skin volume below the eyes, and significantly improved skin hydration as measured on the cheekbone. We show evidence that the tripeptide tetradecyl-diaminobutyroylvalyldiaminobutyric urea trifluoroacetate restores facial skin volume by stimulating HA synthesis. These results underline the anti-aging activity of this synthetic tripeptide.

Treating Aging Changes of Facial Anatomical Layers with Hyaluronic Acid Fillers

“…The dermal elastic fibers become disorganized, and the epidermal mitochondrial network becomes more fragmented with age. 7 These changes result in a loss of skin elasticity and the formation of drier, thinner skin 8 with more rhytids.…”

Designing topical hyaluronic acid technology—Size does matter…

“… Octapeptide (proprietary peptide)—upregulates Hyaluronic Acid Synthase‐2 (HAS2) gene expression in fibroblasts (based on our RNA‐seq data) Lactoferrin—has wound‐healing attributes, promotes fibroblast proliferation, and increases HA secretion 6,7 Syn‐Hycan—synthetic tripeptide that stimulates HA. Published evidence suggests that a synthetic tripeptide tetradecyl aminobutyroylvalylaminobutyric urea trifluoroacetate restores facial skin volume by stimulating HA synthesis 8 . Syn‐Hycan increases HA and CD44 in the skin in vitro and ex vivo 8 …”

“…Published evidence suggests that a synthetic tripeptide tetradecyl aminobutyroylvalylaminobutyric urea trifluoroacetate restores facial skin volume by stimulating HA synthesis 8 . Syn‐Hycan increases HA and CD44 in the skin in vitro and ex vivo 8 Phosphatidylserine—promotes HA synthesis 9 …”

Hyaluronic acid (HA) stimulates the in vitro expression of CD44 proteins but not HAS1 proteins in normal human epidermal keratinocytes (NHEKs) and is HA molecular weight dependent

“…What Mazzucco's data appear to demonstrate is that application of broad molecular weight HA blends to fibroblasts increases the actual expression of CD44 in these cells. This is an important distinction that must be highlighted 15 In earlier reported work, Kaya et al demonstrated that tetradecanoylphorbol acetate (TPA) can also stimulate expression of CD44 in keratinocytes. 16 Kaya's work is important because they demonstrated that CD44 disfunction can disrupt normal HA synthesis in the body and in skin cells.…”

“…Aside from Mazzucco's work, there are few publications that address the ability of ingredients to stimulate the actual expression of CD44 protein. Campiche et al demonstrated that a unique tripepetide, tetradecyl‐diaminobutylvalyldiaminobutyric urea trifluroacetate, has an ability to stimulate CD44 protein synthesis in 3D‐skin equivalent models 15 …”