Immediate and Long-term Clinical Benefits of a Topical Treatment for Facial Lines and Wrinkles

Objective: To evaluate the efficacy and tolerance of a novel line treatment for periocular and perioral wrinkles. The line treatment was formulated with multiple growth factors, antioxidants, and a collagen-building peptide—ingredients that have been shown to increase collagen levels and provide long-term aesthetic benefits. To help provide immediate smoothing effects, hyaluronic acid filling spheres and a muscle contraction-inhibiting peptide were also included in the formulation. Design: Three-month, single-center, open-label, clinical study with clinical assessments at Baseline, Minutes (within 15 minutes of initial application), Month 1, and Month 3. Treatment: Subjects treated periocular and perioral wrinkles twice daily for three months with the line treatment. Participants: Thirty-seven females, 33 to 45 years of age, with mild-to-moderate, fine and coarse periocular and perioral wrinkles, were enrolled in the study. Measurements: Investigator assessments of fine and coarse periocular and perioral wrinkles, digital photography, and tolerance assessments were conducted at all visits. Subject self-assessment questionnaires were conducted within 15 minutes of initial application and at Month 3. Results: Investigator assessments of both periocular and perioral wrinkles showed statistically significant improvements over Baseline within minutes of initial application; these positive findings continued to improve through Months 1 and 3 (all P≤0.0003). No treatment-related adverse events were reported. Conclusions: The results from this study demonstrate that this uniquely formulated line treatment was well tolerated and provided both immediate and long-term improvements in the appearance of fine and coarse wrinkles.One of the most prominent signs of skin aging is the development of fine lines and wrinkles caused by both intrinsic and environmentally induced aging processes.¹ Intrinsic aging is a naturally occurring process relating to chronological age; whereas, environmentally induced aging results from external factors, the most notable of which is ultraviolet (UV) exposure. The main structural changes resulting from both types of aging are characterized by a reduction in collagen and elastin and a loss in hydration; all of which contribute to the appearance of lines and wrinkles. Reactive oxygen species (ROS), a byproduct of both environmentally induced and intrinsic aging, cause a cascade of biochemical reactions within the skin, which results in the production of matrix metalloproteinases (MMPs) and proinflammatory cytokines. MMPs, secreted by fibroblasts and keratinocytes, decrease collagen formation and enhance collagen degradation, contributing to the breakdown of the dermal matrix.^2–4 Proinflammatory cytokines lead to the degradation of elastin and also cause the production of additional ROS.In addition to these structural changes in collagen and elastin, facial areas associated with expression movement, such as the periocular and perioral areas, are especially vulnerable to wrinkle formation. As a result, it can be challenging for physicians and patients to find a topical treatment that produces visible improvement in these areas.To address the challenge of treating expressive facial areas, a topical line treatment containing a combination of ingredients was formulated to provide immediate improvements in the visible signs of aging as well as long-term anti-aging benefits. Multiple growth factors, peptides, and antioxidants were incorporated into the formulation for their ability to increase collagen levels by targeting various biochemical processes involved in collagen production and degradation. In addition, to affect immediate physical improvements in wrinkle appearance, a muscle contraction-inhibiting peptide and dehydrated hyaluronic acid (HA) filling spheres were included in the formulation. The hygroscopic properties of HA and its ability to create and fill space have been well documented.^5,6 The filling spheres, which penetrate into superficial folds of the skin, take advantage of HA’s properties and swell when hydrated, exerting pressure in the direction of the skin surface resulting in a smoothing effect on the skin. To soften the appearance of fine lines, light-diffusing ingredients, such as specialized polymeric microspheres, were also included in the line treatment.In recent years, growth factors have emerged as novel anti-aging agents due to their active role in dermal wound repair.⁷ The significance of the wound-healing process relates to the similarities between the biochemical pathways involved in the aging process and wound formation.⁸ Both processes stimulate the release of growth factors, which affect a variety of biochemical pathways critical to repair of the dermal matrix. In addition, topical growth factors have been shown in clinical studies to decrease the appearance of wrinkles and to stimulate collagen synthesis.^8–11Peptides are another group of novel ingredients included in the line treatment that play an important role in collagen synthesis and degradation. These protein building blocks are used in the body to signal between cells and influence the up- and down-regulation of various cellular functions. One of the peptides included in the treatment, palmitoyl tripeptide-5, is a synthetic peptide that mimics the sequence found in the protein thrombospondin 1 (TSP-1). TSP-1 has been shown to activate latent tissue growth factor β (TGF-β), a growth factor involved in the stimulation of collagen production.^12,13 To aid in the prevention of collagen degradation, the peptide dipalmitoyl hydroxyproline was incorporated for its ability to promote the production of tissue inhibitors of metalloproteinases (TIMPs), thereby suppressing the synthesis of MMPs.¹⁴Another peptide, unrelated to collagen synthesis and degradation, was formulated into the line treatment to target neuromuscular activity. Dipeptide diaminobutyroyl benzylamide diacetate was developed to mimic Waglerin-1, a compound found in temple viper snake venom. Waglerin-1 has been shown to block the nicotinic acetylcholine receptors at the neuromuscular junction, thus inhibiting muscular movement.¹⁵ The function of the Wagerlin-1-mimicking peptide is important for the treatment of lines since facial areas associated with repeated muscle movement are especially susceptible to wrinkle formation.Lastly, the potent antioxidants, ubiquinone and vitamins C and E were incorporated to prevent and reduce oxidative damage, thereby minimizing the effects caused by UV exposure and intrinsic aging.^16–18The purpose of this three-month, open-label, single-center study was to evaluate the efficacy and tolerance of this line treatment for periocular and perioral wrinkles.