A Novel, Volumizing Cosmetic Formulation Significantly Improves the Appearance of Target Glabellar Lines, Nasolabial Folds, and Crow’s Feet in a Double-Blind, Vehicle-Controlled Clinical Trial

January 2014 | Volume 13 | Issue 1 | Original Article | 41 | Copyright © January 2014


Patricia K. Farris MD,a Brenda L. Edison BA,b Ronni L. Weinkauf PhD,b Barbara A. Green RPh MSb

aDepartment of Dermatology, Tulane University School of Medicine, New Orleans, LA
bNeoStrata Company, Inc., Princeton, NJ

Abstract
Facial lines and wrinkles are caused by many factors including constant exposure to external elements, such as UV rays, as well as the dynamic nature of facial expression. Many cosmetic products and procedures provide global improvement to aging skin, whereas injectable therapies are frequently utilized to diminish specific, target wrinkles. Despite their broad availability, some patients are unwilling to undergo injectables and would benefit from an effective topical option. A noninvasive option to volumize target wrinkle areas could also extend benefits of commonly used cosmetic anti-aging products. To this end, a two-step formulation containing the novel, cosmetic anti-aging ingredient, N-acetyl tyrosinamide, was developed for use on targeted wrinkle areas. The tolerability and efficacy of the serum plus cream were tested for 16 weeks in women with moderate facial photodamage on predetermined wrinkle areas (glabellar lines, nasolabial folds, under eye lines, and lateral canthal (crow's feet) wrinkles) in a single-center, randomized, double-blind, vehicle-controlled, clinical trial. Seventy women (47 Active group, 23 Vehicle group) completed the study. Digital photography, clinical grading, ultrasound and self-assessment scores confirmed improvement to wrinkle areas. The topical cosmetic formulation was statistically superior (P<0.05) to its vehicle in visually improving nasolabial folds, glabellar lines, crow’s feet, and under eye wrinkles and in reducing pinch recoil time. Both the test formulation and its vehicle were tolerated well. The novel, two-step cosmetic formulation reduced the appearance of wrinkles and increased skin elasticity thus providing an effective anti-aging option for target wrinkle areas. This study suggests that in addition to its use as monotherapy for reducing targeted lines and wrinkles this cosmetic formulation may be also serve as an adjuvant to injectable therapies.

J Drugs Dermatol. 2014;13(1):41-46.

INTRODUCTION

Facial rhytides arise due to diminished production and increased breakdown of dermal matrix components, including collagen, glycosaminoglycans (GAGs), and elastin, as a result of natural aging and photodamage, coupled with repeated facial movement. Improvement of global photoaging symptoms can be achieved with effective, topical cosmetic formulations which typically address a wide range of skin concerns including dyspigmentation, laxity and surface lines. Physician intervention can provide significant, targeted improvement to wrinkle areas utilizing injectable treatments and a 3-dimensional approach of muscle relaxation, volume restoration and recontouring.1 However, despite their mainstream use in dermatology, injectable therapies may not be ideal for every patient seeking wrinkle reduction. For example, injectables are not completely without risks or discomfort and can be challenging to use on certain areas of the face. In addition, research has confirmed the existence of a needle-averse population and determined that less than 10% of the target population for botulinum toxin A (BoNTA) injections receives treatment.2 Furthermore, the nascent anti-aging patient may be apprehensive to adopt injectables as first-line, anti-wrinkle therapy. The availability of a noninvasive, clinically-proven, topical formulation that reduces the appearance of target lines and wrinkles may prove useful as a cosmetic treatment and potential alternative or adjunct to injectables for certain patients.
A two-step, volumizing formulation has been developed for application to target lines and wrinkles. The product contains a new cosmetic anti-aging ingredient, N-acetyl tyrosinamide, which increases matrix volume to plump and reduce the appearance of facial lines. An objective clinical study was conducted to evaluate the safety and effectiveness of this system in reducing the appearance of target wrinkle areas including glabellar lines, nasolabial folds, lateral canthal (crow’s feet) wrinkles and under eye lines and wrinkles.

Formulation Strategy Incorporating a Novel Volumizing Ingredient

The study products were developed to maximize the benefits of the amino acid compound, N-acetyl tyrosinamide. Independent research of this compound by dermatologist, Eugene J. Van Scott, MD and dermatopharmacologist, Ruey J. Yu PhD OMD was conducted under occlusion to exaggerate penetration and demonstrated a rapid increase in forearm skin thickness. 3 Later, this compound was evaluated in several in vitro and in vivo models
3
table 1
and was shown to favorably impact important dermal matrix markers and provide measurable increases in skin thickness with corresponding anti-aging effects. Specifically, N-acetyl tyrosinamide stimulated collagen production in aged human dermal fibroblast cells4 and increased hyaluronic acid in human dermal fibroblast and chondrocyte (cartilage) cells in vitro.5 Topical application to human skin in vivo with N-acetyl tyrosinamide alone demonstrated a statistically significant increase in forearm skin thickness after 8 weeks of application, as measured by digital calipers. Corresponding histological assessment of skin biopsies showed stimulation of pro-collagen and GAGs, supporting earlier in vitro findings. (Figure 1) Application of N-acetyl tyrosinamide alone to target facial lines and wrinkles (glabellar, crow’s feet, nasolabial folds) demonstrated noticeable visual improvements thus supporting its use as a noninvasive, cosmetic volumizing agent. (Figure 2) In separate testing, this compound was found to be non-photosensitizing, non-phototoxic, non-irritating, non-allergenic and safe for use around the eyes and with contact lenses.5
The test products were formulated as a two-step system in order to mimic the occlusive methodology used in the early development work of N-acetyl tyrosinamide.3 Step 1 is a light serum packaged in a tube with roller ball to facilitate direct application to target wrinkle areas. It contains the cosmetic benefit ingredients, N-acetyl tyrosinamide, N-acetyl hydroxyproline and a low concentration of glycolic acid to aid in delivery. N-acetyl hydroxyproline has been shown to increase skin barrier function6 and is used as an amino acid source for collagen. The Step 2 Finishing Complex is a lightly occlusive cream that is applied directly over Step 1. It contains complementary matrix enhancing ingredients including N-acetyl glucosamine, triethyl citrate plus palmitoyl oligo and tetra peptides (Matrixyl®, Sederma Inc.). N-acetyl glucosamine has been shown to increase hyaluronic acid in human dermal fibroblast cells in vitro, and to increase skin thickness and improve the appearance of fine and coarse wrinkling in vivo.7,8 Triethyl citrate has been shown to increase collagen production in human dermal fibroblast cells in vitro.9

MATERIALS AND METHODS

Study Design

This was a single-center, double-blind, randomized, vehicle-controlled, 16-week clinical study. The protocol was reviewed and approved by a local Institutional Review Board, and all subjects had provided written informed consent before enrollment.
Caucasian women aged 40 to 65 years old, with moderate facial photodamage, defined as a score of 4 to 6 on a 0 to 9 modified Griffith’s scale10, on at least one area including glabellar lines, nasolabial folds, and/or lateral canthal (crow’s feet) wrinkles were eligible for enrollment. In addition, subjects had no known allergies to skincare products, or skin/eye conditions, or uncontrolled chronic diseases that could interfere with evaluations. Other exclusions to participation included: current use of medications for skin or eye conditions; routine use of anti-aging topical products, including prescription retinoids within 6 months; use of hydroxyacids, retinol and other anti-aging cosmetics within 2 months; and/or cosmetic procedures within 6 months.
Enrolled subjects were randomized in a 2:1 ratio to use either the two-step formulation containing anti-aging benefit ingredients (Active group), or their vehicles (Vehicle group). Twice a day for 16 weeks, subjects cleansed their faces with their regular cleanser and those in the Active group treated target wrinkle areas with Step 1 Activator followed by Step 2 Finishing Complex directly over the Step 1 Activator (NeoStrata® Skin Active Line Lift Step 1 Activator and Step 2 Finishing Complex). Those
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