COPPER TRIPEPTIDE-1

Elastic fibers are key components of the skin extracellular matrix and are essential for maintaining skin integrity and elasticity. During skin aging, particularly photoaging, elastic fiber integrity is progressively compromised by increased elastase activity and the downregulation of elastin and scaffold-related gene expression. Therefore, effective strategies to preserve elastic fiber function should address not only elastin synthesis but also enzymatic degradation and scaffold integrity. In this study, we investigated a multitarget approach to restoring the elastic fiber network by modulating elastin production, elastase activity, and scaffold protein expression. We found that Copper Tripeptide-1 enhanced elastin expression and secretion, ethyl ferulate inhibited elastase activity, and cedrol promoted scaffold-related gene expression and microfibrillar protein restoration in dermal fibroblasts. To assess the biological relevance of this approach, the combined treatment was evaluated using UV-damaged human skin biopsy samples. This combination effectively mitigated UV-induced elastic fiber disruption and significantly improved fiber architecture, as confirmed by immunofluorescence staining and scanning electron microscopy. These findings indicate that coordinated modulation of elastin production, proteolytic protection, and scaffold reinforcement is essential for maintaining elastic fiber integrity and represents a promising approach for preserving skin elasticity during aging.

Introduction Skin scars, a natural outcome of dermal injury healing, may seem minor but often lead to significant disfigurement and psychological distress. This study aimed to assess the safety and efficacy of ThriveCo Scar Fader Gel containing Scarcede™ (Anveya Living Private Limited, Bengaluru, India), a proprietary blend of copper tripeptide-1, L-carnitine L-tartrate, alpha-glucosyl hesperidin, and sodium hyaluronate. This synergistic formulation targets multiple scar-improvement mechanisms, offering potential for enhanced skin texture and minimized scar appearance. Method An open-label, interventional, prospective real-world evidence study was conducted to evaluate the clinical safety, efficacy, and in-use tolerability of the test product in females with acne scars. Ethical approval was granted by the Independent Ethics Committee, and informed consent was obtained from all participants. Visible scar changes were assessed using the Manchester Scoring Scale by a dermatologist. Skin texture changes, including smoothness, roughness, and scaliness, were evaluated using VISIOSCAN® VC20 Plus (Courage + Khazaka electronic GmbH, Cologne, Germany). Digital photographs documented progressive scar visibility reduction. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 29.0.1.0 (Released 2022; IBM Corp., Armonk, New York) and Microsoft® Excel 2019 (Microsoft Corporation, Redmond, Washington), with significance reported at the 5% level. Result The test product reduced scar appearance by 7.17% at day 21 (p<0.001) and 26.57% at day 45 (p<0.0001). Skin smoothness improved by 33.08% at day 21 (p<0.0001) and 44.56% at day 45 (p<0.0001). Skin roughness decreased by 100.86% at day 21 (p<0.0001) and 161.62% at day 45 (p<0.0001). Scaliness reduced by 39.71% at day 21 (p<0.001) and 58.92% at day 45 (p<0.0001). No local or systemic adverse effects were reported. Conclusion ThriveCo Scar Fader Gel with Scarcede™ demonstrated clinical safety and efficacy in scar reduction, supporting smoother, clearer skin without adverse effects and suitable for routine skincare use.

Background and objective Scalp dandruff, a prevalent dermatological condition marked by flaking and itching, affects a large segment of the population. Sun exposure, genetics, and dryness, along with winter conditions, indoor heating, and hard water, all contribute to moisture loss and scalp imbalance. This study aimed to evaluate the safety, efficacy, and tolerability of a novel regimen combining a scalp scrub with hydroxy acid derivatives for exfoliation and dandruff removal, and a serum containing copper tripeptide-1, witch hazel ( Hamamelis virginiana) , hesperidin, hyaluronic acid, and pea protein ( Pisum sativum ) for hydration and scalp health. Methods This prospective, interventional, open-label, single-center study assessed the safety, efficacy, and in-use tolerability of a scalp scrub and serum regimen for mild to moderate dandruff. Ethical approval was granted by ACEAS - Independent Ethics Committee and all participants provided written consent. The study evaluated changes in Adherent Scalp Flaking Score (ASFS), scalp hydration with the Corneometer ® CM 825, hair thickness, hair density, and scalp condition using CASLite Nova. Scalp appearance and treatment usage perception were evaluated on day 1, day 8, and day 15. Statistical analysis was conducted using SPSS Statistics v29.0.1.0 (IBM Corp., Armonk, NY) and Microsoft Excel 2019, with results reported as p-values and 95% confidence intervals (CI). Results As per the ASFS scale for adherent scalp flaking, a significant improvement of 61.24% (p<0.0001) was observed by day 15. Assessments with CASLite Nova showed significant increases in hair density and hair thickness by 12.48% (p<0.0001) and 25.36% (p<0.0001), respectively. Regarding scalp condition, the proportion of individuals with a dry scalp and significant keratin decreased from 65.52% at baseline to 6.9% by day 15. The incidence of dry scalp with fine dandruff also decreased from 6.9% at baseline to 0% by day 15. Conversely, the percentage of individuals with a dry scalp and some keratin increased from 27.59% at baseline to 48.28% by day 15. Also, the proportion of subjects with a normal scalp, characterized by good hair density and thickness, increased from 0% at baseline to 44.83% by day 15. Scalp skin hydration, measured by Corneometer® CM 825, showed a significant improvement of 76.24% (p<0.0001) from baseline to day 15. Overall, there were notable enhancements in scalp appearance, with reductions in itchiness, redness, roughness, and scaliness. All subjects reported satisfaction with the treatment. Conclusions The ThriveCo scalp regimen (scalp scrub + serum) has been demonstrated to be both effective and safe in treating and reducing scalp dandruff in healthy adults. The regimen significantly reduced ASFS by effectively removing visible scalp flakes from day 1 to day 15 with continuous use. Furthermore, the kit improved overall scalp condition, increased skin hydration, and enhanced the scalp's appearance. The components include scalp scrub with hydroxy acid derivatives for exfoliation and dandruff removal, and a serum containing copper tripeptide-1, Hamamelis virginiana , hesperidin, hyaluronic acid, and pea protein ( Pisum sativum ) for hydration and overall scalp health over the 15-day treatment period. The synergistic effects of this regimen work to clear visible dandruff flakes, reduce adherent scalp flaking, rejuvenate the scalp, and simultaneously strengthen the hair.

Research has shown the efficacy of hair growth factors in hair regrowth. We describe the intradermal injections of a recombinant, bioengineered hair formulation, containing growth factors, into the scalp skin, for enhancement of hair regrowth and evaluate its efficacy. The objective of this study was to assess the efficacy and safety of the hair growth factor formulation in reducing hair loss and enhancing hair growth. This was an open-label, prospective, single-arm interventional pilot study in which 1000 patients were given intradermal injections of a hair formulation into the scalp skin. The formulation contains vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor, keratinocyte growth factor, thymosin β4, and copper tripeptide-1 suspended in a sterile injectable vehicle. Intradermal injections of this hair formulation were injected into the scalp once every 3 weeks for a total of eight such sessions. Hair pull test was performed before every session. Videomicroscopic and global images were taken at baseline, fourth session, eighth session, and 2 months after the completion of the eight sessions. Relevant safety assessments through physical examination, questionnaires, and appropriate laboratory examination were conducted throughout the study. Significant reduction in hair fall was seen in 83% of the patients on hair pull test. Videomicroscopic image evaluation showed that most patients had a decrease in the number of vellus hairs, increase in number of terminal hairs, and increase in shaft diameter. Seventy-five percent of the patients believed that the hair injections were aiding the treatment of their hair loss, and it was also beneficial in post-hair transplant patients. At 1 year, a statistically significant increase in total hair count (P = 0.002) continued to be seen. Treatment was well tolerated. Intradermal injections of this hair formulation may be a promising option for treating male as well as female patterns of hair loss.

To evaluate the effect of copper tripeptide and tretinoin on normal and keloid-producing dermal fibroblasts in a serum-free in vitro model. The cellular response was described in terms of viability and secretion of basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-beta1). Primary cell lines were established from patient facial skin samples obtained during surgery and plated in serum-free media. At 0 hour, copper tripeptide (1 x 10 (-9) mol/L), tretinoin (1 x 10 (-5) mol/L), or appropriate control vehicle was added. Cell counts and viability were established at 24, 72, and 120 hours. Supernatants were collected at the same intervals and were assessed for bFGF and TGF-beta1 concentrations using the enzyme-linked immunosorbent assay technique. Cell lines showed viability between 86% and 96% (mean, 92%) throughout the experiment. Tretinoin-treated normal fibroblasts secreted more bFGF than did controls at 24 hours (P<.05). Tretinoin-treated keloid-producing fibroblasts secreted more TGF-beta1 than did controls at 120 hours (P<.05). Keloid-producing fibroblasts treated with copper tripeptide secreted less TGF-beta1 than did controls at 24 hours (P<.05); a similar trend was observed in normal fibroblasts. Normal fibroblasts treated with tretinoin produced more bFGF than did controls, and this might partially explain the clinically observed tightening effects of tretinoin. Normal and keloid-producing dermal fibroblasts treated with copper tripeptide secreted less TGF-beta1 than did controls, suggesting a possible clinical use for decreasing excessive scar formation.

Current treatment modalities are limited in their approach and success for hair loss. QR 678 & QR 678 Neo are new formulations, consisting of a combination of growth factors and peptides. This study demonstrates safety analysis of QR 678 & QR 678 Neo formulation, using in vitro cytotoxicity assay and in vivo animal efficacy. Factors including vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor-1, keratinocyte growth factor, and copper tripeptide 1 (QR 678) or their biomimetic peptides (QR678 Neo) were suspended in a sterile injectable vehicle. The 3-2,5-diphenyl tetrazolium bromide assay was used to explore the cytotoxic effects of each factor used in the compositions in human keratinocyte cell and human fibroblast cell assays. An in vivo analysis, wherein study animals were given intradermal QR 678 & QR 678 Neo injections, was conducted to assess whether the formulations produce hair growth. Also, hair follicle viability was checked by intradermal injection of the pharmaceutical compositions in secondary alopecia. In both formulations, a positive response was observed with respect to the number of mice exhibiting hair growth at the injection sites. The injections caused retention of hair in a 0.25-cm radius around the injection site. On cytotoxicity study, all the factors were found to be safe in human keratinocyte cell and human fibroblast cell assay. A positive response was demonstrated in animals on treatment with the chemotherapeutic agent. Intradermal injections of QR 678 & QR 678 Neo hair growth factor formulations are a safe and efficacious option for alopecia. Results seem encouraging enough to warrant a trial in humans with secondary alopecia, post cancer chemotherapy.

The human peptide GHK (glycyl-l-histidyl-l-lysine) has multiple biological actions, all of which, according to our current knowledge, appear to be health positive. It stimulates blood vessel and nerve outgrowth, increases collagen, elastin, and glycosaminoglycan synthesis, as well as supports the function of dermal fibroblasts. GHK’s ability to improve tissue repair has been demonstrated for skin, lung connective tissue, boney tissue, liver, and stomach lining. GHK has also been found to possess powerful cell protective actions, such as multiple anti-cancer activities and anti-inflammatory actions, lung protection and restoration of chronic obstructive pulmonary disease (COPD) fibroblasts, suppression of molecules thought to accelerate the diseases of aging such as NFκB, anti-anxiety, anti-pain and anti-aggression activities, DNA repair, and activation of cell cleansing via the proteasome system. Recent genetic data may explain such diverse protective and healing actions of one molecule, revealing multiple biochemical pathways regulated by GHK.

Peptides are promising and attractive anti-wrinkle active ingredients, amongst which glycyl-histidyl-lysine peptide (GHK) is one of the most broadly promoted peptide for topical application. This simple sequence of amino acid residues not only has the capability of tissue regeneration and the enhancement of collagen and glycosaminoglycans synthesis but also is able to increase nerve outgrowth and angiogenesis. Consequently, GHK has several properties, from wound healing to prevention/reduction wrinkles. GHK-Cu and Pal-GHK are metal complex and palmitoylated derivatives of GHK, respectively. Although GHK-Cu and Pal-GHK are widely used in anti-wrinkle products available on the cosmetic market, the published information on their skin permeability, effectiveness, physicochemical properties and so on is insufficient. This review aims to highlight whether GHK is sufficiently effective on wrinkle prevention/reduction. Apart from the effectiveness, another question that is tried to be answered is whether skin permeability of GHK allows it to act as an anti-wrinkle peptide at its site of action? Skin permeation enhancement methods employed so far are also reviewed. Based on cellular studies, undoubtedly, GHK can be considered as an anti-wrinkle ingredient. Although GHK-Cu and Pal-GHK have been of interest as effective peptides to be incorporated in the anti-wrinkle products, there is a surprising absence of clinical studies using them. Metal complexation and chemical modification with a hydrophobic moiety increase permeability of this peptide. Besides, cell penetrating peptides seem promising to increase skin permeation of GHK and its derivatives. Skin pretreatment with microneedles also has the potential to be further studied for permeation enhancement of such peptides. As peptide ingredients, their formulation may encounter some challenges, mainly due to their hydrophilic (high aqueous solubility and low partition coefficient) and unstable nature. Although GHK-Cu and Pal-GHK are effective and relatively skin permeable, their permeability could be successfully increased using permeation enhancement methodologies.

Oxidative stress, disrupted copper homeostasis, and neuroinflammation due to overproduction of proinflammatory cytokines are considered leading causative factors in development of age-associated neurodegenerative conditions. Recently, a new mechanism of aging-detrimental epigenetic modifications-has emerged. Thus, compounds that possess antioxidant, anti-inflammatory activity as well as compounds capable of restoring copper balance and proper gene functioning may be able to prevent age-associated cognitive decline and ward off many common neurodegenerative conditions. The aim of this paper is to bring attention to a compound with a long history of safe use in wound healing and antiaging skin care. The human tripeptide GHK was discovered in 1973 as an activity in human albumin that caused old human liver tissue to synthesize proteins like younger tissue. It has high affinity for copper ions and easily forms a copper complex or GHK-Cu. In addition, GHK possesses a plethora of other regenerative and protective actions including antioxidant, anti-inflammatory, and wound healing properties. Recent studies revealed its ability to up- and downregulate a large number of human genes including those that are critical for neuronal development and maintenance. We propose GHK tripeptide as a possible therapeutic agent against age-associated neurodegeneration and cognitive decline.