Article

Evaluation of anti-wrinkle efficacy of adenosine-containing products using the FOITS technique

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Abstract

The objective of this study was to evaluate formulations containing adenosine to reduce periorbital lines and glabellar frowns in a blind, randomised, placebo-controlled study. One hundred twenty-six female volunteers between 45 and 65 years of age fulfilled inclusion criteria for periorbital lines. They were provided with two of three products (cream with adenosine, dissolvable film with adenosine or placebo), to be applied to the periorbital area on each side of the face (84 subjects per product). Eighty-four of these subjects also fulfilled the inclusion criteria for glabellar frowns, and received placebo or cream with adenosine to be applied to the glabellar area. Products were applied twice daily for 2 months, and evaluation was performed under dermatological supervision at 0, 3 and 8 weeks using Fast Optical in vivo Topometry of human Skin (FOITS) analysis to describe skin profile. Both adenosine-containing products led to significant improvements in skin smoothness in the periorbital area. Improvements were evidenced after 3 weeks of product application as measured by Ra and Rz parameters using the FOITS technique, and were steadily confirmed after 2 months, despite severe climatic conditions and independently of the analysis technique that was used with the FOITS data. Adenosine-containing cream also significantly improved glabellar frowns. This study demonstrates the potential beneficial effects of adenosine-containing products on crow's feet and glabellar facial wrinkles.

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... Each calibration curve showed good linear regression as follows: uridine (1) Pyrimidine nucleoside uridine has been shown to rapidly restore the ocular surface in patients with dry eye by increasing hyaluronic acid synthesis, reducing degradative enzymes, such as matrix metalloproteinase-9, and enhancing the number of goblet cells [42]. Adenosine is a naturally occurring purine nucleoside formed by the breakdown of adenosine triphosphate, which is a member of an important class of bioactive molecules with antiwrinkle properties [43]. Therefore, Pyrimidine nucleoside uridine has been shown to rapidly restore the ocular surface in patients with dry eye by increasing hyaluronic acid synthesis, reducing degradative enzymes, such as matrix metalloproteinase-9, and enhancing the number of goblet cells [42]. ...
... Therefore, Pyrimidine nucleoside uridine has been shown to rapidly restore the ocular surface in patients with dry eye by increasing hyaluronic acid synthesis, reducing degradative enzymes, such as matrix metalloproteinase-9, and enhancing the number of goblet cells [42]. Adenosine is a naturally occurring purine nucleoside formed by the breakdown of adenosine triphosphate, which is a member of an important class of bioactive molecules with antiwrinkle properties [43]. Therefore, adenosine has been applied in cosmetic preparations to improve facial wrinkles. ...
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... In this study, we compared adenosine-loaded DMNs (Ad-DMN) with an adenosine cream (Ad-Cream), which is known to improve crow's feet wrinkles [22]. We fabricated Ad-DMNs by using centrifugal lithography [23], which exerts less stress on the drug-loaded DMNs, minimizing the activity loss than other DMN fabricating methods [24]. ...
... Transdermal delivery of therapeutics or functional substrates, which are widely used for skin-mediated drug treatment, is patient friendly and can be used as an alternative for oral drug delivery, which causes drug degradation in the digestive system and has a low absorption rate [1][2][3][4]. Topical application of formulations, such as ointments and creams, is mostly used for various cosmetic skincare treatments, such as skin hydration, skin depigmentation, and anti-wrinkling [5][6][7]. They are also used for skin-mediated treatment targeting local skin diseases, such as skin melasma, atopic dermatitis, and psoriasis [8][9][10][11]. ...
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... 59 The data from this study suggest that, in the long-term use, cosmetic products containing Ado can significantly reduce existing wrinkles in the two facial areas studied, partially reversing the signs of chronological aging. 62 Ado may be incorporated into a transdermal patch or soluble microneedle patch that is applied to the skin. In all cases, the adenosine-loaded dissolving microneedle patches showed a similar or better efficacy than the Ado cream, although in one case the weekly Ado dose was 140 times lower. ...
Article
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Skin aging is a complex biological process. Skin aspect is considered as a sign of well‐being and of beauty. In view of this, noninvasive and/or minimally invasive anti‐aging strategies were developed. Adenosine, a well‐known nucleoside, may play a role in skin rejuvenation. Adenosine receptors belong to the G protein‐coupled receptors superfamily and are divided into four subtypes: A1, A2A, A2B, and A3. The adenosine receptors expressed by skin are mainly the A1 and A2A subtypes. In the hypodermis, adenosine through the A1 receptor stimulates lipogenesis and adipogenesis. In the dermis, adenosine through the A2A receptor subtype stimulates collagen production. Moreover, the nucleoside increases new DNA synthesis and subsequently protein synthesis in dermal cells. Activation of adenosine receptors by interacting with various skin layers may induce a decrease in the amount of wrinkles, roughness, dryness, and laxity. This article has reviewed the mechanisms through which adenosine modulates biological mechanisms in the skin tissues and the effect of preparations containing adenosine or its derivatives on the skin.
... Topical application of adenosine has been used to promote hair growth and skin health [34,35]. The hair follicle is one of the most energy consuming organs in humans. ...
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In the present study, we investigated the molecular mechanisms of adenosine for its hair growth promoting effect. Adenosine stimulated the Wnt/β-catenin pathway by modulating the activity of Gsk3β in cultured human dermal papilla cells. It also activated adenosine receptor signaling, increasing intracellular cAMP level, and subsequently stimulating the cAMP mediated cellular energy metabolism. The phosphorylation of CREB, mTOR, and GSK3β was increased. Furthermore, the expression of β-catenin target genes such as Axin2, Lef1, and growth factors (bFGF, FGF7, IGF-1) was also enhanced. The inhibitor study data conducted in Wnt reporter cells and in cultured human dermal papilla cells demonstrated that adenosine stimulates Wnt/β-catenin signaling through the activation of the adenosine receptor and Gsk3β plays a critical role in transmitting the signals from the adenosine receptor to β-catenin, possibly via the Gαs/cAMP/PKA/mTOR signaling cascade.
... Adenosine has been trialed on non-injured skin as a topical antiwrinkle treatment, with indication of beneficial effects. 51 However, modern dermal treatments incorporate microneedling into topical treatments, so there is some concern that adenosine in such contexts may lead to the formation of scars. It has been shown that the synthetic partial agonist of the A 2A R, known as CGS21680, did not activate Smad2/3 and instead modulated the expression of other A 2A R effectors, increasing the ratio of collagen-1/ collagen-3. ...
Article
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One of the side‐effects of oral anti‐aging retinoids is increased hair shedding. Retinoids promote the expression of TGF‐β2 from fibroblasts, which stimulate collagen expression but silences keratinocytes. Since keratinocytes normally influence differentiation of dermal papilla cells at the base of the hair follicle, retinoids feasibly inhibit hair growth via the increased expression of TGF‐β2, which inhibits Wnt/β‐catenin signalling. Fortunately, the plant kingdom provides an array of alternatives as dual‐acting nutricosmetics and topicals that work independently of TGF‐β2 to confer dermal anti‐aging and hair health effects. These alternatives include ‘plant hormones’ such as cytokinins and phytoestrogens. Many cytokinins are agonists of the G‐coupled adenosine receptors. Partial agonism of adenosine receptors promotes collagen synthesis independently of TGF‐β2 signalling. Adenosine expression is potentially also the mechanism of minoxidil in promotion of scalp hair growth. Because of crosstalk between adenosine and cannabinoid receptors it makes sense to try combinations of specific CB2 agonists and cytokinins (or phytoestrogens). However, dual‐acting cosmetics including peptides with high numbers of positively charged amino acids, such as lysine or arginine, offer real potential as they can be processed from multiple botanical candidates, including almond, fenugreek, pea sprouts, soy, and seaweeds. The current review summarises much of what is known about retinoid alternatives in the plant kingdom and identifies potentially fruitful new areas of research.
... 20 When applied onto the skin, it exerts a potent anti-wrinkle action and is currently the active ingredient of many commercial anti-ageing creams. 21 ...
Article
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Skin appearance is essential for self‐esteem and quality of life, consequently, skin care products represent a huge market. In particular, cosmeceuticals constitute a hybrid category of skin care formulations, at the interphase of cosmetics and pharmaceuticals, rationally designed to target (patho)physiological mechanisms aiming to enhance skin health and appearance. Cosmeceuticals are marketed as anti‐aging, anti‐wrinkle, hair regrowth, skin whitening and wound healing agents with special emphasis on scar‐free healing. An overview on recent cutting‐edge advances concerning the discovery and development of enhanced performance cosmeceuticals by drug repositioning approaches is presented here. In this context, we propose “target repositioning”, a new term, to highlight that druggable protein targets implicated in multiple diseases (hubs in the diseasome) can be exploited to accelerate the discovery of molecularly targeted cosmeceuticals that can promote skin health as an added benefit, which is a novel concept not described before. In this direction, emphasis is placed on the role of mouse models, for often untreatable skin diseases, as well as recent breakthroughs on monogenic rare skin syndromes, in promoting compound repositioning to innovative cosmeceuticals.
... Based on the studies of skin wrinkles, some of the materials were stimulating fibroblast growth. Adenosine (AD) (molecular weight, 267.24 g/mol; adenine-9-β-D-ribofuranoside) is an active pharmaceutical ingredient for the treatment of skin wrinkles [6][7][8][9]. It exerts its pharmacological effect through the A 2A receptors, which are one of the AD related receptors in cells and stimulate collagen production from primary human dermal fibroblasts [6,10]. ...
Article
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Adenosine (AD), which is used for treating wrinkles, exhibits poor skin permeation. The aim of the present study was to develop a cross-linked silicone-based cellulose elastomer as an elastic artificial skin for the treatment of skin wrinkles, a biocompatible lipid-based nano-carrier for enhancing the skin permeation of AD, and a formulation consisting of the lipid-based carrier incorporated in the elastic artificial skin. AD-loaded solid lipid nanoparticles (SLNs) were prepared using a double-emulsion method. Particle characteristics and mechanical properties of SLNs and elastic artificial skin, respectively, were assessed. Skin permeation was evaluated using SkinEthic RHE tissue, a reconstructed human epidermis model. The mean particle size and zeta potential for SLNs ranged from 123.57 to 248.90 nm and −13.23 to −41.23 mV, respectively. The components of neither SLNs nor the elastic artificial skin were cytotoxic, according to cell- and tissue-viability assays and EU classification. SLNs and the elastic artificial skin exhibited sustained drug release for 48 h. The amount of AD released from SLNs and elastic artificial skin was approximately 10 times and 5 times higher, respectively, than that from AD solution. Therefore, elastic artificial skin incorporated with AD-loaded SLNs may serve as a promising topical delivery system for cosmeceutical treatment of skin wrinkles.
... These derivatives are susceptible to enzymatic hydrolysis by tissue esterase and a-glucosidase, thereby yielding ascorbic acid [21][22][23]. Adenosine exhibits anti-wrinkle properties [24], and it is mostly used as an active ingredient in anti-wrinkle and combination of whitening and anti-wrinkle cosmetics in the Republic of Korea. ...
Article
OBJECTIVE: The Korean Cosmetic Act regulates the use of functional cosmetics) by the law. Four functional cosmetic groups, whitening, anti-wrinkle, UV protection and combination of whitening and anti-wrinkle, were categorized according to the Korean Cosmetic Act and Functional Cosmetics Codex. In this study, high-performance liquid chromatography (HPLC) coupled with photodi-ode array detection (DAD) was employed for the simultaneous detection of arbutin (and its decomposition product, hydro-quinone), niacinamide, ascorbyl glucoside, ethyl ascorbyl ether and adenosine in functional cosmetic products such as creams, emulsions and lotions. METHODS: Separation by HPLC-DAD was conducted using a C18 column with a gradient elution of 5 mM KH2PO4 buffer (containing 0.1% phosphoric acid) and methanol (containing 0.1% phosphoric acid). The wavelengths for the detection of arbutin, hydroquinone, niacinamide, adenosine, ascorbyl glucoside and ethyl ascorbyl ether were 283, 289, 261, 257, 238 and 245 nm, respectively. RESULTS: This method exhibited good linearity (R 2 ≥ 0.999), precision (expressed as relative standard deviation (RSD) < 2%) and mean recoveries (89.42-104.89%). The results obtained by monitoring 100 market samples showed that the detected levels of the tested materials are within the acceptable authorized concentration. CONCLUSION: The method developed herein is simple and can be used for market survey and quality control of functional cosmetics. R esum e OBJECTIF: La Loi Cosm etique cor eenne r eglemente l'utilisation de cosm etiques ou de produits fonctionnels). Quatre groupes cosm eti-ques fonctionnels, a savoir les blanchissants ment, les anti-rides, les anti-UV, et les combinaisons de blanchiment et anti-rides, ont et e class es selon la r eglementation cosm etique cor eenne et le Codex des Functional Cosmetics. Dans cette etude, la Chromatographie liquide a haute performance (HPLC) coupl ee a une d etection a r eseau de photodiodes (DAD) a et e utilis ee pour la d etection simul-tan ee de l'arbutine (et son produit de d egradation, l'hydroquinone), du niacinamide, du glucoside d'ascorbyle, de l' ether d'ascorbyle d' ethyle, et de l'ad enosine dans les produits cosm etiques fonction-nels tels que les cr emes, emulsions, lotions etc. METHODES: La s eparation par HPLC-DAD a et e effectu ee en utili-sant une colonne C18 avec un gradient d' elution d'un tampon 5 mM KH2PO4 (contenant 0.1% d'acide phosphorique) et de m etha-nol (contenant 0.1% d'acide phosphorique). Les longueurs d'onde pour la d etection de l'arbutine, de l'hydroquinone, du niacinamide, de l'ad enosine, du glucoside d'ascorbyle, de l' ether l'ascorbyl d' ethyle sont 283, 289, 261, 257, 238 et 245 nm, respectivement. R ESULTATS: Cette m ethode pr esente une bonne lin earit e (R 2 ≥ 0.999), une pr ecision inf erieure a 2% (exprim ee en ecart-type relatif (RSD), et des recouvrements moyens (89.42 de-104.89%). Les r esultats obtenus en analysant les 100 echantillons du march e ont montr e que les taux des substances test ees se situ-ent dans les limites des concentrations autoris ees. CONCLUSION: La m ethode d evelopp ee ici est simple et peutêtre utilis ee pour l' etude du march e et le contrôle de qualit e des pro-duits cosm etiques fonctionnels.
... Adenosine applied topically has been used to promote hair growth and skin health (Abella, 2006;Faghihi et al., 2013). For the treatment of androgenetic alopecia, adenosine (0.75% solution) displayed efficacy similar to minoxidil but was preferred by patients because of the response speed and its quality. ...
Article
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Adenosine receptors (ARs) function in the body’s response to conditions of pathology and stress associated with a functional imbalance, such as in the supply and demand of energy/oxygen/nutrients. Extracellular adenosine concentrations vary widely to raise or lower the basal activation of four subtypes of ARs. Endogenous adenosine can correct an energy imbalance during hypoxia and other stress, for example, by slowing the heart rate by A1AR activation or increasing the blood supply to heart muscle by the A2AAR. Moreover, exogenous AR agonists, antagonists, or allosteric modulators can be applied for therapeutic benefit, and medicinal chemists working toward that goal have reported thousands of such agents. Thus, numerous clinical trials have ensued, using promising agents to modulate adenosinergic signaling, most of which have not succeeded. Currently, short-acting, parenteral agonists, adenosine and Regadenoson, are the only AR agonists approved for human use. However, new concepts and compounds are currently being developed and applied toward preclinical and clinical evaluation, and initial results are encouraging. This review focuses on key compounds as AR agonists and positive allosteric modulators (PAMs) for disease treatment or diagnosis. AR agonists for treating inflammation, pain, cancer, non-alcoholic steatohepatitis, angina, sickle cell disease, ischemic conditions and diabetes have been under development. Multiple clinical trials with two A3AR agonists are ongoing.
... 47 Other components of skincare regimens used in combination with BoNT-A include hydroquinone for skin lightening, and adenosine, which has been proposed to act by a number of mechanisms to reduce wrinkles and improve skin tone and texture. 48 Use of such a skin care regimen by individuals who have had BoNT-A injections has been demonstrated to have a beneficial effect on the mean volume and depth of facial lines, hyperpigmentation, smoothness of skin, and evenness of skin tone and color compared with BoNT-A injections alone. 33,38 A "microbotox" method of BoNT-A application has recently been developed. ...
Article
Full-text available
BotulinumtoxinA (BoNT-A) is now widely established for the main approved indication of reducing glabellar lines, and is also widely used off-label to improve the appearance of wrinkles and lines in other parts of the face. The number of aesthetic procedures continues to increase as the patient population becomes more diverse, in particular with increasing numbers of people of color and men. Further developments in treatment may continue to expand the audience for BoNT-A by making procedures more comfortable and by delivering a more natural, less static appearance. These may be achieved through use of combinations of BoNT-A with other aesthetic procedures, tailoring the dose of toxin to the patient’s muscle mass or by using novel injection and application techniques. Beyond amelioration of facial lines, encouraging results have been seen with the use of BoNT-A to improve the appearance of hypertrophic and keloid scars and even to prevent them. Studies have been conducted with scars in various parts of the body and further research is ongoing. Dermatological and other medical uses for BoNT-A are also active areas of research. Injections of BoNT-A have been shown to reduce signs and symptoms of acne, rosacea, and psoriasis, to reduce neuromuscular pain, and to bring about significant improvements in a number of rare diseases that are caused or exacerbated by hyperhidrosis. This paper reviews these new uses for BoNT-A, looking at the rationale for their use and discussing the results of published case studies and clinical trials. These areas have shown great promise to date, but more and larger clinical studies will be required before these treatments become a clinical reality. To this end details are also provided of clinical trials currently listed in the main clinical trials database to highlight research areas of particular interest.
... These derivatives are susceptible to enzymatic hydrolysis by tissue esterase and a-glucosidase, thereby yielding ascorbic acid [21][22][23]. Adenosine exhibits anti-wrinkle properties [24], and it is mostly used as an active ingredient in anti-wrinkle and combination of whitening and anti-wrinkle cosmetics in the Republic of Korea. ...
... The technology of these instruments is constantly being updated and their accuracy is further improving. The area of skin imaging has exploded in recent years with 2D and 3D image analysis devices and software readily available to quantify features such as size of pores; eye bags; facial wrinkles; scalp hair; cellulite [29][30][31][32][33][34][35][36]. All of these approaches provide quantitative results that can be further exploited as percentage variation (e.g. ...
Article
Full-text available
The main regulatory frameworks governing the cosmetic industry dates back to 1938 in the United States (US) and 40 years later in Europe (EU). Since then, both the US and EU cosmetic legislations have inspired the regulatory framework of a number of countries working toward harmonisation of cosmetics legislation. During the years the requirements for the efficacy of cosmetic products have been implemented to adapt them to the state of the art; however no clear guidelines for efficacy testing on cosmetic products exist. The lack of guidelines and/or shared position on cosmetic testing represents the missing link between the regulatory requirements and the consumer protection from misleading claims in the real life. On the other side a regulatory claimed prerequisite is ineffective if clear and specific testing methodologies are not available to the cosmetic industry. This introduce a discretionary element decreasing the strength of the original regulatory requirement, having an impact on consumer protection from misleading claims, and sometimes decreasing the credibility of the cosmetic product in the marketplace. Initiatives aimed at developing clear, specific for cosmetic products, and effective guidelines should arrive from the academy, industry, and professional associations. This manuscript is aimed to give an overview of the main ethical, technical and regulatory concerns affecting the design of an efficacy study carried out on humans.
... Adenosine exhibits anti-wrinkle properties [24], and it is mostly used as an active ingredient ...
Article
Objective: The Korean Cosmetic Act regulates the use of functional cosmetics or cosmeceuticals) by the law. Four functional cosmetic groups, whitening, anti-wrinkle, UV protection, and combination of whitening and anti-wrinkle, were categorized according to the Korean Cosmetic Act and Functional Cosmetics Codex. In this study, high-performance liquid chromatography (HPLC) coupled with photodiode array detection (DAD) was employed for the simultaneous detection of arbutin (and its decomposed product, hydroquinone), niacinamide, ascorbyl glucoside, ethyl ascorbyl ether, and adenosine in functional cosmetic products such as cream, emulsion, and lotion. Methods: Separation by HPLC-DAD was conducted using a C18 column with a gradient elution of 5 mM KH2 PO4 buffer (containing 0.1% phosphoric acid) and methanol (containing 0.1% phosphoric acid). The wavelengths for the detection of arbutin, hydroquinone, niacinamide, adenosine, ascorbyl glucoside, and ethyl ascorbyl ether were 283, 289, 261, 257, 238, and 245 nm, respectively. Results: This method exhibited good linearity (R(2) ≥ 0.999), precision (expressed as relative standard deviation (RSD) < 2%), and mean recoveries (89.42% - 104.89%). The results obtained by monitoring 100 market samples showed that the detected levels of the tested materials are within the acceptable authorized concentration. Conclusion: The method developed herein is simple and can be used for market survey and quality control of functional cosmetics. This article is protected by copyright. All rights reserved.
... Increases in levels of collagen types I and III provide resiliency and strength to skin. Another constituent, adenosine, has also been shown to be effective in treating wrinkles [13]. Adenosine acts as a regulator of cellular and organ function, and interacts with a family of 4G protein-coupled receptors, A 1 , A 2A , A 2B and A 3 . ...
... Moreover, Bissett et al. (2004) and Kawada et al. (2008) reported that topical niacinamide treatments and cosmetics containing niacinamide have antiwrinkle effects. Adenosine is a naturally occurring purine nucleoside formed by the breakdown of adenosine triphosphate (Xue et al. 2009) that also shows antiwrinkle properties (Abella 2006). ...
Article
Full-text available
A reversed-phase high-performance liquid chromatography method using a diode array detector at 260 nm was developed and validated for the determination of arbutin, niacinamide, and adenosine in cosmetics. The analytes were extracted using methanol and deionized water. The separations were performed on a C18 column with gradient elution. At the optimized conditions, the limits of detection for arbutin, niacinamide, and adenosine were 0.75, 0.12, and 0.01 lg/mL, respectively. The average recoveries were between 98.1% and 107.5%. The method was used to analyze thirty cosmetics.
... As shown inFigure 3, strong positive correlations (coefficients r 2 = 0.99) were found in the present study between the content of purine nucleoside compounds (Table S4) and antioxidant activities (Table 5). Adenosine is also known to act as an antiwrinkle compound for human skin [51,52].Thus, cultivated fruit bodies of C. bassiana at stage 3 might be considered natural resources for nutraceuticals with free-radical scavenging activity or as cosmeceutical materials with antiwrinkle activity. ...
Article
Full-text available
The metabolic profiles of Cordyceps bassiana according to fruiting body developmental stage were investigated using gas chromatography-mass spectrometry. We were able to detect 62 metabolites, including 48 metabolites from 70% methanol extracts and 14 metabolites from 100% n-hexane extracts. These metabolites were classified as alcohols, amino acids, organic acids, phosphoric acids, purine nucleosides and bases, sugars, saturated fatty acids, unsaturated fatty acids, or fatty amides. Significant changes in metabolite levels were found according to developmental stage. Relative levels of amino acids, purine nucleosides, and sugars were higher in development stage 3 than in the other stages. Among the amino acids, valine, isoleucine, lysine, histidine, glutamine, and aspartic acid, which are associated with ABC transporters and aminoacyl-tRNA biosynthesis, also showed higher levels in stage 3 samples. The free radical scavenging activities, which were significantly higher in stage 3 than in the other stages, showed a positive correlation with purine nucleoside metabolites such as adenosine, guanosine, and inosine. These results not only show metabolic profiles, but also suggest the metabolic pathways associated with fruiting body development stages in cultivated C. bassiana.
... There is increasing evidence documenting the effects of 'antiaging' cosmetic moisturizers on the signs of photodamaged skin. Typical agents used in these moisturiz-ers include hydroxyacids, 1,2 retinol, and its esters, 3,4 salicyloylphytosphingosine, 5 peptides, [6][7][8][9] adenosine, 10 niacinamide, 11 creatine and folic acid, 12 peroxisomal proliferator activated receptor agonists, 13 hyaluronic acid fragments, 14 and a variety of antioxidants including ascorbic acid 15 and lipoic acid. 16 Many of these agents have complex effects on the skin ranging from increasing dermoepidermal membrane restructuring through to inhibition of matrix metalloprotease activity and improving epidermal differentiation all of which are perturbed in photodamaged skin. ...
Article
Background: Cumulative lifetime sun exposure is accepted as having a very important role to play in the expression of the signs of photoaging, which is then superimposed on the intrinsic processes involved in the chronological aging of skin. Many groups have evaluated the effects of emulsion-based products, mostly although not exclusively, on the face using a variety of actives including retinoids and antioxidants. Nevertheless, the effect of a topical anhydrous product on photodamaged skin has not been reported in the literature. Aims: The objective of this study was to clinically evaluate the effect of a vitamin A palmitate and antioxidant-containing oil-based moisturizer on facial, neck, decolletage, arms, and lower leg body sites. Methods: In a randomized, controlled and efficacy grader-blinded clinical study conducted over 12 weeks, while at the same time recording the changes in skin condition for a no-treatment group over the same time period, live clinical expert grading of all body sites and also grading of photographs for the face and neck assessed changes in the signs of photodamage was performed for the treatment and no-treatment groups. Results: Compared to the no-treatment group, and to baseline, the oil improved fine lines, coarse wrinkles, mottled pigmentation, uneven skin tone, roughness, firmness, and clarity of the skin on the face and neck and was also shown to improve crepey skin texture, dryness, scaling and roughness on the decolletage, arms and lower legs at the primary end point at 12 weeks (P < 0.001). Moreover, improvements in a variety of parameters were observed as quickly as 2 weeks. In general, the degree of improvement was greatest in the order legs > arms > decolletage > face > neck. Conclusions: Collectively, these results show the cumulative improvements in the signs of photoaging compared to a no-treatment control group for the oil-based antiaging moisturizer for the first time. The differences in the efficacy of the vitamin A palmiate and antioxidant oil-based moisturizer on different body sites probably reflect the differences in likely photodamage.
... This compares favorably with other studies using similar methods and known anti-aging ingredients. 35,36,[38][39][40][41] Third, we evaluated the clinical effect of the SScontaining formulation in a randomized double-blind, placebo-controlled study via visual and photographic grading on subjects displaying moderate skin photodamage. For the expert grading of the periorbital area, both the placebo and the SS-containing formulation improved relative to baseline but the latter was superior to its placebo at both 4 and 8 weeks. ...
Article
Anti-aging effects of high concentrations of salicylic acid (SA) peels are commonly known. Like all acids, SA can produce somatosensory and visible irritation to the skin and as such may be unsuitable for subjects with sensitive skin. To provide evidence that sodium salicylate (SS) obtained from neutralization of 1% SA by sodium hydroxide can deliver significant anti-aging benefits. The effects of SS were examined using three approaches: (1) evaluating its effects on stimulating the synthesis of fibrillin and collagen-1 in vivo; (2) examining its efficacy by using Fast Optical in vivo Topometry (FOITS) in a double-blind, placebo-controlled clinical study; (3) determining its effects on both expert and naïve grader assessement of wrinkles in a double-blind, placebo-controlled study. In the first study SS produced significant increases of the fibrillin and collagen-1 anti-aging biomarkers compared with the untreated skin control. A commercially available retinol cream delivered similar effects to SS. In the second study using FOITS we showed that the SS formulation significantly reduced wrinkle depth (Rz) and skin roughness (Ra) after 4 and 8 weeks of daily application vs. placebo (Rz: -8.2 ± 1.40% and -11.4 ± 1.07%; Ra: -7.8 ± 1.33% and -11.9 ± 0.61%; P < 0.01). In the third study reductions in wrinkle depth were observed by expert assessment at both 4 and 8 weeks for the SS-containing formulation compared to its placebo (P < 0.05). Equally, non-expert graders recorded the SS formulation superior to its placebo. Although the mechanism of action is not completely understood, we believe the benefits of SS are derived from its intrinsic stratum corneum exfoliation effects. All three studies demonstrate the significant anti-aging effects of SS that are especially suitable for subjects with sensitive skin.
Article
This work portrays the simultaneous electrochemical analysis of adenine and adenosine on a poly-nicotinic acid modified pencil graphite electrode (poly-NA/PGE). The electrochemical behavior of the PGE and poly-NA/PGE were analyzed using cyclic voltammetry and electrochemical impedance spectroscopy. Morphological comparison of the PGE and modified PGE were done with field emission scanning electron microscopy and atomic force microscopy. Faradaic response of adenine and adenosine were observed on poly-NA/PGE at 0.95 V and 1.23 V, respectively, at neutral pH. Using differential pulse voltammetric technique, the sensor demonstrated a linear response to both adenine and adenosine from 2.0—70 µM concentration range with lower detection limits of 0.9276 μM and 0.8794 μM, respectively. The feasibility of the developed electrochemical device was also studied in blood serum and urine samples and was found to be a remarkable tool for the simultaneous electroanalysis of adenine and adenosine.
Article
Background Sonophoresis can increase the delivery efficiency of various drugs into the skin. A recent advance in sonophoresis is the use of ultrasound-responsive liquid-core nuclei (URLN) to increase the probability of cavitation. In this study, we developed a URLN and ultrasound device, and demonstrated its effectiveness through in vitro and clinical tests. Materials and methods Three types of experiments were designed to evaluate the efficiency of sonophoresis with URLN. First, a Franz diffusion cell with cosmetic ingredients was used to analyze quantitatively the amount of drug delivered to the porcine skin. Second, after the application of sonophoresis with URLN, the porcine skin surface was examined using scanning electron microscopy (SEM) to see the changes in morphology. Finally, a clinical test was performed to verify the utility of sonophoresis with URLN. Results The results indicate that sonophoresis with URLN can increase the amount of compound delivered by approximately 11.9-fold over 6 h for niacinamide and by 7.33-fold over 6 h for adenosine. In addition, we observed approximately 20–30 μm sized pores on porcine skin in SEM images. In clinical testing, the application of sonophoresis with cosmetics containing URLN for 3 min improved the efficiency of transdermal drug delivery by 1.9-fold, the depth of absorption by 2.0-fold, and the speed of absorption by 2.0-fold at 30 min after application. Conclusion We expect that sonophoresis with specialized URLN in transdermal drug delivery could be used widely for various skin-related applications.
Article
Self-healing, thermo-responsive hydrogels have received increasing attention for tissue engineering, drug delivery, and cosmetic applications. Here, a thermo-responsive hydrogel with self-healing properties was prepared from methylcellulose (MC) and a water-soluble chitosan oligomer (CHI-O). First, dialdehyde methylcellulose (DAMC) derivative was synthesized from MC via periodate oxidation, and its rheological behavior was investigated according to the degree of oxidation. Next, dual-crosslinked DAMC/CHI-O copolymer hydrogels were obtained via Schiff base formation between the aldehyde group of DAMC and the amino group of CHI-O. These hydrogels were chemically linked by imine bonds and physically linked through hydrophobic interactions originating from MC. Based on rheological and compression tests, the gelation rate, mechanical properties, and self-healing properties of the copolymer hydrogels are compared with those of the MC hydrogel. Finally, the release of model compounds (adenosine and L-ascorbic acid) from the DAMC/CHI-O copolymer hydrogel was studied as a preliminary test for cosmetic applications.
Chapter
This chapter details the process of claims substantiation, how claims can be generated, supported, and communicated. It looks at the definition of cosmetic claims and what may be required to substantiate them. It builds on an approach to substantiating cosmetic claims developed in the UK by the CTPA in association with the ASA. This includes defining different classes of claims, the level of evidence required to support the classes, and also the quality of evidence that might be anticipated by an advertising regulator or an in market competent authority. Though it is written from a UK/EU market view, the recognition that clearly identified consumer needs, and how these are fulfilled by the final product, form an essential part of claims development making the approach described in this chapter applicable globally. The chapter also raises the challenges presented by advances in understanding of skin physiology, the technology that can be applied to influencing this and how this might be communicated to consumers.
Article
Herein we report for the first time, a simultaneous voltammetric sensor for adenosine, adenine and uric acid using a pencil graphite (PG) substrate electropolymerised with 2-amino-5-mercapto-1,3,4-thiadiazole in phosphate buffer with pH 7. The developed sensor was characterized morphologically, structurally and electrochemically. Under the optimum conditions, a linear concentration range of 0.2–25.6 µM, 0.05–12.8 µM and 5–1200 µM was obtained with a detection limit of 0.19 µM, 0.039 µM and 2.74 µM for adenosine, adenine and uric acid respectively. Viability of the sensor was also tested in blood and urine samples, and it was found that the sensor is an excellent tool for the simultaneous determination of the above mentioned targets.
Article
Background Dissolving microneedles (DMNs) have been used for skin restoration and wrinkle improvement. Although lipophilic compounds, for example, natural oils or ceramides, enrich the skin barrier, their delivery via DMNs is challenging because of DMN fabrication difficulties. Objectives In the present study, we combined a topical formulation and a DMN patch to perform two‐phase delivery comprising a lipophilic formulation and hydrophilic compound‐loaded DMNs to improve skin barrier status and the efficacy of drug delivery. Methods Horse oil‐spread and adenosine‐loaded DMN arrays were developed in a single patch (HOS‐Ad‐DMN patch). In vitro analysis was conducted to confirm the successful delivery of the compositions. Clinical assessments were conducted on the lateral canthus of 20 women to compare the efficacy of HOS‐Ad‐DMN patches with that of adenosine‐loaded DMN patches (Ad‐DMN patches). Results Adenosine was delivered via the DMNs after skin penetration and horse oil was delivered successfully into the skin through the microchannels created by the Ad‐DMNs. Compared with Ad‐DMN patches, HOS‐Ad‐DMN patches significantly improved skin elasticity, hydration, dermal density, and wrinkles. No adverse events were observed. Conclusion HOS‐Ad‐DMN patches are a safe and efficient system for skin restoration and wrinkle improvement.
Article
Objective Although dissolving microneedle patches have been widely studied in the cosmetics field, no comparisons have been drawn with the topical applications available for routine use. In this study, two wrinkle‐improving products, adenosine‐loaded dissolving microneedle patches and an adenosine cream, were evaluated for efficacy, with respect to skin wrinkling, dermal density, elasticity, and hydration, and safety in a clinical test on the crow's feet area. Methods Clinical efficacy and safety tests were performed for 10 weeks on 22 female subjects with wrinkles around their eyes. The adenosine‐loaded dissolving microneedle patch was applied once every 3 days, in the evening, for 8 weeks to the designated crow's feet area. The adenosine cream was applied two times per day, in the morning and evening, for 8 weeks to the other crow's feet area. Skin wrinkling, dermal density, elasticity, and hydration were measured by using PRIMOS® premium, Dermascan® C, Cutometer® MPA580, and Corneometer® CM 825, respectively. In addition, subjective skin irritation was evaluated by self‐observation, and objective skin irritation was assessed through expert interviews. Results The adenosine‐loaded dissolving microneedle patches had a similar or better efficacy than the adenosine cream. Both groups showed statistically significant efficacy for almost all parameters (P < 0.05). The dissolving microneedle patches had a long‐lasting effect on the average wrinkle depth (P < 0.05), only showed efficacy in dermal density (P < 0.05), had an early improving effect on elasticity (P < 0.05), and demonstrated better hydration efficacy (P < 0.001). No adverse effects were observed in either group during the test period. Conclusions In the clinical efficacy test of four skin‐improvement parameters, adenosine‐loaded dissolving microneedle patches showed the same or better effect than the adenosine cream, although the weekly adenosine dose was 140 times lower. The dissolving microneedle patches caused no adverse reactions. These adenosine‐loaded dissolving microneedle patches are expected to be safe, effective, and novel cosmetics for skin improvement. This article is protected by copyright. All rights reserved.
Article
Background: Various kinds of functional cosmetics are on the market, although there are a variety of opinions concerning the actual effect. Transdermal microneedle patch has been introduced as a newly developed device for drug delivery through the skin. Objective: This study was conducted to verify the face skin improvement effect and safety of a novel cosmetic microneedle patch. Methods: A total of 84 Korean females finished this prospective clinical trial. The subjects were divided into 3 groups: (1) soluble hyaluronic acid (HA) microneedle patch alone, (2) soluble HA microneedle patch plus adenosine wrinkle cream, and (3) adenosine wrinkle cream alone. The treatments were applied to the crow's feet and nasolabial fold wrinkle for 12 weeks. The test areas were measured before treatment and at 4, 8, and 12 weeks after use of the test product. At the completion of the testing period of the trial, the global assessment of efficacy and product preferences were surveyed from the subjects. Results: Combination treatment with wrinkle cream and microneedle patch significantly improved Merz scale for crow's feet and nasolabial folds, compared to the sole application of wrinkle cream or patch. Measurement on the crow's feet showed an overall improvement in all 3 groups, yielding no significant differences among the groups. No serious adverse effects were observed during the follow-up period. Conclusion: Combination application of a soluble microneedle patch and wrinkle cream was an effective treatment in improving facial wrinkles, thus enhancing skin rejuvenation.
Article
This chapter details the process of claims substantiation, how claims can be generated, supported and communicated. It looks at the definition of cosmetic claims and what may be required to substantiate them. It details an approach to substantiating cosmetic claims based on an approach developed in the UK by the Cosmetics Toiletries & Perfumers Association (CTPA) in association with the Advertising Standards Authority (ASA). This includes the different classes of claims, the level of evidence required to support the classes and also the quality of evidence required to support a claim. The approach emphasises the fact that the consumer needs and how these are fulfilled is an essential part of the thinking. The chapter also raises the challenges presented by advances in the understanding of skin physiology, the technology that can be applied to influencing this and how this might be communicated to consumers.
Article
Oriental herbs are reported as having potent functions for preventing many types of diseases. They also appear to have positive effects and potential capabilities for skin care. Among the many oriental herbs that are available, we chose to analyze four medicinal herbs, Korean red ginseng, Artemisia capillaries Thunb, Schizonepeta tenuifolia Briq, and Foeniculum vulgare Mill, because all are popular and considered as favorite medicinal plants in Korea. Extracts of the herbs were obtained by various methods such as using distilled water, ethyl ether, methanol, ethanol, benzene, 1-butanol, and chloroform. Nine phytochemicals were detected in the extracts: maltol, adenosine, b-pinene, menthone, pulegone, limonene, anethole, estragole, and fenchone, which reportedly have multi-functionalities. All phytochemicals were analyzed quantitatively by various chromatographic techniques such as HPLC and gas chromatography-mass (GC-MS) spectrometry. This article also presents the optimum conditions for extracting these 9 targeted phytochemical compounds that were derived from 4 popular oriental herbs, which could be useful for the efficient preparation of each phytochemical.
Article
Introduction: A monocentre double-blind two parallel group clinical study was conducted to assess whether a new skincare regimen containing retinol, adenosine and hyaluronic acid, applied after the injection of botulinum toxin A to the glabellar area, provided a beneficial effect. Material and methods: Standardised photographs acquired using LifeViz cameras and zoomed pictures of the glabella and of the crow's feet areas were analysed with automatic well-defined procedures. Perceived efficacy and tolerance were also analysed by comparison between the two groups. Results: A beneficial effect versus placebo-treated group was proven in the group having topically applied the new skincare regimen for 2 months following botulinum toxin A injection with no touch up after 1 month. 3D image analysis showed more rapid results on D10 and enhanced efficacy on M2. Moreover, a beneficial effect independent of injection was measured in the crow's feet area, and analysis of the self-evaluation questionnaire showed enhanced efficacy perceived by the volunteers. Conclusion: A specially developed skincare regimen applied immediately after botulinum toxin A injection completes the beneficial effect of the injection on the glabellar area and offers clinical benefits in fine lines, wrinkles and smoothness on the whole face.
Article
Basement membranes are thin structures present in the extracellular matrix that provide a supporting framework on which epithelial and endothelial cells reside. Type IV collagen is present ubiquitously in all basement membranes and plays an important role in cell adhesion, migration differentiation, and growth. These are especially important at the dermoepidermal junction (DEJ) in skin. A reduction in the levels of DEJ proteins occurs in photodamaged skin and especially Type IV collagen at the base of a wrinkle. In these studies, the ability of a triple peptide complex (TPC) to stimulate the production of collagen IV in human skin fibroblasts and its effects on photoaged skin was investigated. Fibroblasts, matured to represent "aged" cells, were stimulated for 72 h with the TPC as well as the three individual peptides constituting the complex, and collagen IV production by the fibroblasts was determined immunochemically. The results show that stimulation with the individual peptides at doses found in 1% (v/v) of the TPC did not result in soluble collagen IV production above levels detected by the non-stimulated cells. However, after stimulation with 1% (v/v) of the TPC, collagen IV was produced by the cells (1.4 ng/ng total protein +/- 0.4 SD, n = 5) when compared to control un-stimulated cells (0.32 ng/ng total protein +/- 0.1 SD, n = 5). This indicates that the combination of the individual peptides is necessary to synergistically stimulate collagen IV production. These findings suggest that the TPC could play a role in the strengthening of the DEJ through its ability to produce collagen IV. In order to determine whether these results translated into significant effects in vivo, we performed two studies. In the first four-week study, a double blind, placebo-controlled and fully randomized clinical study on 22 healthy Caucasian volunteers displaying moderate periorbital wrinkles, a significant reduction in wrinkle parameters determined by profilometry was observed over the 4-week period in comparison to the placebo. This result was reproduced in a 12-week monadic study which also showed improvements in expertly graded wrinkle scores. Collectively, these results effectively demonstrate the anti-aging applications of the TPC.
Article
The periorbital area is a key wrinkle-prone region, where the first signs of aging usually appear. To demonstrate the ability of new anti-aging moisturizing products to improve overall smoothness and wrinkle depth appearance in the periorbital region via the Fast Optical in vivo Topometry of Human Skin (FOITS). Two double-blind, randomized, controlled, split-face studies (n = 42, Study 1; n = 35, Study 2) were conducted in women 30-70 years old with moderate to distinct periorbital wrinkles. Subjects applied 0.5 g of individual products to half their face twice daily for 4 weeks. Four test products containing niacinamide, the peptides Pal-KT and Pal-KTTKS, and carnosine were used and included a daytime SPF 30 lotion also containing antioxidants, a night cream, an eye cream also containing caffeine, and a wrinkle treatment containing retinyl propionate. The wrinkle treatment was only tested in Study 2. The FOITS technique was used to measure changes in periorbital R(a) (mean roughness) and R(z) (average maximum roughness) at 2 and 4 weeks. In Study 1, the daytime SPF 30 lotion, night cream, and eye cream significantly improved crow's feet smoothness after 4 weeks relative to no treatment. After 4 weeks, the daytime SPF 30 lotion and night cream, but not the eye cream, were significantly better than no treatment at improving R(z). In Study 2, the night cream, eye cream, and wrinkle treatment, but not the daytime SPF 30 lotion, significantly improved both R(a) and R(z) after 4 weeks. To increase power and precision of estimates, a meta-analysis was performed; the pooled data showed all three products were significantly better than no treatment at improving R(a) and R(z) after 4 weeks. Four weeks of treatment with these products was shown to improve the smoothness of periorbital skin and to reduce the apparent depth of larger wrinkles.
Article
A water-dissolvable film was developed to topically deliver adenosine for a localized anti-wrinkle effect. The polymers used to produce the film were cellulose derivatives. An aqueous mixture of the film components was made, coated on a liner, and then dried to form a solid film. No preservatives were added and the film was shown to be stable over time. The film quickly dissolves in water to form a uniform layer at the surface of the skin, as shown by scanning electron microscopy. The film layer can still be visualized on the wrinkle six hours after being applied on the skin. A randomized, placebo-controlled, investigator-blind study was conducted in female volunteers to assess the efficacy of the 1% adenosine-containing dissolvable film. After three weeks and eight weeks, a twice daily application led to a significant decrease in the skin roughness parameters as observed using fast optical in vivo topometry (FOITS). These results demonstrate that water-dissolvable films may be used as novel, preservative-free, cosmetic delivery systems.
Chapter
First investigations about contactless surface analysis of the skin were initialized in the year 1995. After a successful validation phase, the first publication of the new FOITS technology (Fast Optical In Vivo Topometry of Human Skin) can be found in 1997 [1]. In comparison to the replica-driven technique during the last decade, the touch-free technique of fringe projection became state of the art to investigate skin surface [2–5]. Due to many technical advancements (as, e.g., improved camera resolution, the use of blue LED lighting systems, or laser-supported and computer-optimized overlaying procedures), an easy-to-operate system could be realized during the last years. As scientific interest on the mechanisms of wrinkle evaluation has always been pushed, the technical developments led to a tool of high scientific standard [6–9]. From the beginnings in the year 1995, FOITS became worldwide established. Today it is used in various countries (Germany, France, Great Britain, Ireland, Italy, the USA, China, Japan, and South Korea). Consequently, in 2012, the new generation FOITS-2 is now available to realize a one-shot one-face technique with an excellent resolution and time regime.
Article
皮膚は, 主として表皮と真皮より構成されるが, その境界部には基底膜が存在する。この表皮基底膜は, アンカリング複合体を形成して表皮と真皮を強く繋ぎ止めている。表皮基底膜は, さらに, 表皮細胞の分化増殖を制御し, 表皮の極性の維持にも寄与している。この表皮基底膜は, 加齢とともに多重化, 断裂という構造変化が起こる。特に, 顔面皮膚では, 「お肌の曲がり角」といわれる20代後半から30代前半に急激に構造変化が起こっている。この変化は, 皮溝皮丘の加齢に伴う変化とほぼ一致し, 老化の初期変化, 「初期老化」と定義できる。これが将来のしわ・たるみなどの老徴の出現を促進させる要因と考えられる。したがって, 基底膜を健康に保つことは老化の進行を遅らせるためのスキンケアとして重要な機軸であるといえる。ラミニン5は, アンカリング複合体を構成する糖蛋白質で, 表皮基底膜に存在し, 表皮が真皮へ接着するために重要な働きをしている。精製ラミニン5は, 三次元培養皮膚および表皮シート移植試験において基底膜形成促進活性をもつ。さらに, ラミニン5産生促進物質もまた, ラミニン5と同様に基底膜形成促進作用を示す。したがって, ラミニン5, ラミニン5産生促進物質は「基底膜ケア」のキー物質である。
Article
In a 16-week randomized, double-blind, vehicle-controlled study of topical tretinoin in the treatment of photoaging, all patients applied topical tretinoin to one forearm and vehicle cream to the other. Half of the patients received tretinoin to the face, and half received vehicle cream. All 30 patients who completed the study showed statistically significant improvement in photoaging on the tretinoin-treated forearms, but not on the vehicle-treated forearms. Fourteen of the 15 patients who received tretinoin to the face had improvement in photoaging, whereas none of the vehicle-treated patients' faces improved, a statistically significant difference in response between the two groups. Statistically significant histologic changes were seen in forearm skin treated with tretinoin, but not with vehicle cream. Side effects were limited to irritation of tretinoin-exposed skin.
Article
Wrinkles now have a greater social impact because people live longer. Science and hedonism overlap in the search for causes, treatments and prevention of wrinkles. The cosmetic approach to wrinkles includes: Active ingredients go well beyond simple moisturisers and exert a more complex activity in protecting skin from external injuries, nourishing it and removing its superficial layers. Transport systems and excipients are increasingly effective. Functional agents currently include alpha hydroxy acids (AHAs), poly-AHAs, complex poly-AHAs, retinoids, fish polysaccharides, anti-enzymatic agents, antioxidants (including ascorbic acid, pycnogenol, ursolic acid, vegetable isoflavones, vitamin E, coenzyme Q10, lipoic acid, resveratorol, l-carnosine and taurine) as well as agaricic acid and various plant extracts. All are reviewed in this text. Most are topical, some can be given by mouth, even as food supplements. Cosmetics are becoming closer to drugs in preventing and treating wrinkles. Included amongst the cosmeceuticals are the anti-wrinkle agents described herein.
Studies on cutaneous ageing: the elastin fibre network
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Braverman, I.M. and Fornferko, E. Studies on cutaneous ageing: the elastin fibre network. J. Invest. Dermatol. 78, 434-443 (1982).
Skin surface claim supported by FOITS
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Skin surface claim supported by FOITS
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