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Polycomponent mesotherapy formulations for the treatment of skin aging and improvement of skin quality

Skin aging can largely be attributed to dermal fibroblast dysfunction and a decrease in their biosynthetic activity. Regardless of the underlying causes, aging fibroblasts begin to produce elements of the extracellular matrix in amounts that are insufficient to maintain the youthful appearance of skin. The goal of mesopreparations is primarily to slow down and correct changes in skin due to aging. The rationale for developing complex polycomponent mesopreparations is based on the principle that aging skin needs to be supplied with the various substrates that are key to the adequate functioning of the fibroblast. The quintessential example of a polycomponent formulation – NCTF® (New Cellular Treatment Factor) – includes vitamins, minerals, amino acids, nucleotides, coenzymes and antioxidants, as well as hyaluronic acid, designed to help fibroblasts function more efficiently by providing a more optimal environment for biochemical processes and energy generation, as well as resisting the effects of oxidative stress. In vitro experiments suggest that there is a significant increase in the synthetic and prophylactic activity of fibroblasts with treated NCTF, and a significant increase in the ability of cells to resist oxidative stress. The current article looks at the rationale behind the development of polycomponent mesopreparations, using NCTF as an example.

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Bioactive reagents used in mesotherapy for skin rejuvenation in vivo induce diverse physiological processes in human skin fibroblasts in vitro- a pilot study.

The promise of mesotherapy is maintenance and/or recovery of a youthful skin with a firm, bright and moisturized texture. Currently applied medications employ microinjections of hyaluronic acid, vitamins, minerals and amino acids into the superficial layer of the skin. However, the molecular and cellular processes underlying mesotherapy are still elusive. Here we analysed the effect of five distinct medication formulas on pivotal parameters involved in skin ageing, that is collagen expression, cell proliferation and morphological changes using normal human skin fibroblast cultures in vitro. Whereas in the presence of hyaluronic acid, NCTF135(®) and NCTF135HA(®) , cell proliferation was comparable to control cultures; however, with higher expression of collagen type-1, matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, addition of Soluvit(®) N and Meso-BK led to apoptosis and/or necrosis of human fibroblasts. The data indicate that bioactive reagents currently applied for skin rejuvenation elicit strikingly divergent physiological processes in human skin fibroblast in vitro.

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Platelet-rich plasma combined with fractional laser therapy for skin rejuvenation.

Platelet-rich plasma (PRP) is an autologous concentration of human platelets contained in a small volume of plasma and has recently been shown to accelerate wound healing and rejuvenate aging skin. The current study was conducted to determine whether there are additional effects of PRP combined with fractional laser therapy.

Twenty-two Korean women underwent three sessions of fractional laser; 11 were treated with topical application of PRP combined with fractional laser. Evaluations were done at baseline and 1 month after the final treatment. The outcome assessments included subjective satisfaction scale; blinded clinical assessment; and the biophysical parameters of roughness, elasticity, skin hydration, and the erythema and melanin index. Biopsies were analyzed using hematoxylin and eosin, Masson-trichrome, and immunohistochemistry for matrix metalloproteinase-1.

PRP combined with fractional laser increased subject satisfaction and skin elasticity and decreased the erythema index. PRP increased the length of the dermoepidermal junction, the amount of collagen, and the number of fibroblasts.

PRP with fractional laser treatment is a good combination therapy for skin rejuvenation. Keratinocyte and fibroblast proliferation and collagen production can explain the capacity of PRP to increase dermal elasticity.

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Essential fatty acid metabolism and its modification in atopic eczema

Research from the 1930s to the 1950s established that a deficit of n26 essential fatty acids (EFAs) leads to an inflammatory skin condition in both animals and humans. In a common inherited skin condition, atopic dermatitis (eczema), there was evidence of low blood EFA concentrations and of a therapeutic response to exceptionally high doses of linoleic acid. More recently, it has been established that there is no deficit of linoleic acid in atopic eczema. Concentrations of linoleic acid instead tend to be elevated in blood, milk, and adipose tissue of patients with atopic eczema, whereas concentrations of linoleic acid metabolites are substantially reduced. This suggests reduced conversion of linoleic acid to g-linolenic acid (GLA). In most but not all studies, administration of GLA has been found to improve the clinically assessed skin condition, the objectively assessed skin roughness, and the elevated blood catecholamine concentrations of patients with atopic eczema. Atopic eczema may be a minor inherited abnormality of EFA metabolism.

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The Use of Hyaluronidase in Cosmetic Dermatology: A Review of the Literature

Background: Hyaluronidase can be employed to manage a variety of complications associated with cosmetic hyaluronic acid (HA) filler injection. However, the indications and treatment protocol for hyaluronidase use have not been well established.
Objective: Review of the available literature to describe the use of hyaluronidase in the reversal of HA filler injection.
Methods: PubMed/MEDLINE databases were utilized to identify case reports and studies pertaining to the use of hyaluronidase after HA filler injection.
Results: Hyaluronidase can be successfully employed in the management of uncomplicated nodules and overcorrection, inflamed nodules, or tissue ischemia associated with HA filler injection. Hyaluronidase use is dependent on the clinical indication, anatomical location, and original injected HA quantity.
Conclusion: Hyaluronidase is an important tool for clinicians utilizing cosmetic HA filler injection. Further reports and studies are warranted to firmly establish the ideal treatment protocol.

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The Use of Phosphatidylcholine for Correction of Lower Lid Bulging Due to Prominent Fat Pads

Background. Patients with prominent periorbital fat pads often complain of having a persistent “tired” look and seek treatment from their dermatologist.
Objective. A non-surgical treatment of fat pads.
Methods. Thirty patients were treated for prominent lower eyelid fat pads with phosphatidylcholine injection. Pre- and posttreatment photographs were taken for long-term Analysis. results. A marked reduction of the lower eyelid fat pads was noted over the 2-year follow-up period. There were no recurrences.
Conclusion. The injection of phosphatidylcholine (250 mg/5ml) into the fat pads is a simple office procedure that may postpone or even substitute for lower eyelid blepharoplasty.

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A Report on Three Recent Clinical Trials Using Mahonia aquifolium 10% Topical Cream and a Review of the Worldwide Clinical Experience With Mahonia aquifolium for the Treatment of Plaque Psoriasis

This monograph summarizes 3 recent clinical trials and the worldwide clinical experience with Mahonia aquifolium in patients with psoriasis. Study 1 was an open-label study to evaluate the safety of Mahonia aquifolium in 39 patients treated for 12 weeks. Assessments made were modified PASI, global assessment, psoriasis history questionnaire, Dermatology Life Quality Index, and Psoriasis Disability Index. The results indicate statistically significant improvement in PASI score and Dermatology Life Quality Index after 4 weeks of treatment. This response continued 1 month after the end of treatment. Study 2 was a clinical trial of 32 patients with mild to moderate bilateral psoriasis treated up to 6 months. One side of the body received Mahonia and the other standard psoriatic treatment (eg, Dovonex cream). The primary outcomes were patient ratings of the Mahoniatreated side alone and the comparison between treatments received on each side of their body.

Eighty-four percent of patients rated the Mahonia-treated psoriasis as good to excellent response. When compared with standard treatment, 63% of patients rated Mahonia aquifolium equal to or better than the standard psoriatic treatment. Study 3 was an observational study of 33 patients with mild to moderate bilateral psoriasis treated for 1 month. The results indicate improvement in psoriasis after 1 week of treatment. The side treated with Mahonia did as well or better than the side treated with the vehicle cream. Results from these 3 open-label clinical trials are in agreement with published data that include placebo-controlled studies. Taken together, these clinical studies conducted by several investigators in several countries indicate that Mahonia aquifolium is a safe and effective treatment of patients with mild to moderate psoriasis.

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The treatment of atopic dermatitis with licorice gel

Glycyrrhiza glabra L. has been used in herbal medicine for skin eruptions, including dermatitis, eczema, pruritus and cysts. The effect of licorice extract as topical preparation was evaluated on atopic dermatitis. The plant was collected and extracted by percolation with suitable solvent. The extract was standardized, based on Glycyrrhizinic acid by using a titrimetry method. Different topical gels were formulated by using different cosolvents. After standardizing of topical preparations, the best formulations (1% and 2%) were studied in a double–blind clinical trial in comparison with base gel on atopic dermatitis over two weeks (30 patients in each group). Propylene glycol was the best co-solvent for the extract and Carbopol 940 as gelling agent showed the best results in final formulations. The quantity of glycyrrhizinic acid was determined 20.3% in the extract and 19.6% in the topical preparation. Two percent licorice topical gel was more effectivethan 1% in reducing the scores for erythema, oedema and itching over two weeks (p,0.05). The results showed that licorice extract could be considered as an effective agent for treatment of atopic dermatitis.

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Biological and Pharmacological Activities of Squalene and Related Compounds: Potential Uses in Cosmetic Dermatology

Squalene is a triterpene that is an intermediate in the cholesterol biosynthesis pathway. It was so named because of its occurrence in shark liver oil, which contains large quantities and is considered its richest source. However, it is widely distributed in nature, with reasonable amounts found in olive oil, palm oil, wheat-germ oil, amaranth oil, and rice bran oil. Squalene, the main component of skin surface polyunsaturated lipids, shows some advantages for the skin as an emollient and antioxidant, and for hydration and its antitumor activities. It is also used as a material in topically applied vehicles such as lipid emulsions and nanostructured lipid carriers (NLCs). Substances related to squalene, including β-carotene, coenzyme Q10 (ubiquinone) and vitamins A, E, and K, are also included in this review article to introduce their benefits to skin physiology. We summarize investigations performed in previous reports from both in vitro and in vivo models.

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A systematic review of natural health product treatment for vitiligo

Background: Vitiligo is a hypopigmentation disorder affecting 1 to 4% of the world population.Fifty percent of cases appear before the age of 20 years old, and the disfigurement results in psychiatric morbidity in 16 to 35% of those affected.

Methods: Our objective was to complete a comprehensive, systematic review of the published scientific literature to identify natural health products (NHP) such as vitamins, herbs and other supplements that may have efficacy in the treatment of vitiligo. We searched eight databases including MEDLINE and EMBASE for vitiligo, leucoderma, and various NHP terms. Prospective controlled clinical human trials were identified and assessed for quality.

Results: Fifteen clinical trials were identified, and organized into four categories based on the NHP used for treatment. 1) L-phenylalanine monotherapy was assessed in one trial, and as an adjuvant to phototherapy in three trials. All reported beneficial effects. 2) Three clinical trials utilized different traditional Chinese medicine products. Although each traditional Chinese medicine trial reported benefit in the active groups, the quality of the trials was poor. 3) Six trials investigated the use of plants in the treatment of vitiligo, four using plants as photosensitizing agents. The studies provide weak evidence that photosensitizing plants can be effective in conjunction with phototherapy, and moderate evidence that Ginkgo biloba monotherapy can be useful for vitiligo. 4) Two clinical trials investigated the use of vitamins in the therapy of vitiligo. One tested oral cobalamin with folic acid, and found no significant improvement over control. Another trial combined vitamin E with phototherapy and reported significantly better repigmentation over phototherapy only. It was not possible to pool the data from any studies for meta-analytic purposes due to the wide difference in outcome measures and poor quality ofreporting.

Conclusion: Reports investigating the efficacy of NHPs for vitiligo exist, but are of poor methodological quality and contain significant reporting flaws. L-phenylalanine used with phototherapy, and oral Ginkgo biloba as monotherapy show promise and warrant further investigation.

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Cytoprotective Effect of Green Tea Extract and Quercetin against Hydrogen Peroxide-Induced Oxidative Stress

In this study, we evaluated the cytoprotective effects of antioxidative substances in hydrogen peroxide (H 2 O 2 ) treated Mel-Ab melanocytes. Tested substances include selenium, quercetin, green tea (GT) extract, and several vitamins (ascorbic acid, Trolox, and folic acid). Of these,
both quercetin and GT extract were found to have strong cytoprotective effects on H 2 O 2 - induced cell death. We also examined additive effects, but no combination of two of any of the above substances was found to act synergistically against oxidative damage in Mel-Ab cells.
Nevertheless, a multi-combination of GT extract, quercetin, and folic acid appeared to prevent cellular damage in a synergistic manner, which suggests that combinations of antioxidants may be of importance, and that co-treatment with antioxidants offers a possible means of treat-ing vitiligo, which is known to be related to melanocyte oxidative stress.

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Topical use of dexpanthenol: a 70th anniversary article

Approximately 70 years ago, the first topical dexpanthenol-containing formulation (Bepanthen TM Ointment) has been developed. Nowadays, various topical dexpanthenol preparations exist, tailored according to individual requirements. Topical dexpanthenol has emerged as frequently used formulation in the field of dermatology and skin care. Various studies confirmed dexpanthenol’s moisturizing and skin barrier enhancing potential. It prevents skin irritation, stimulates skin regeneration and promotes wound healing. Two main directions in the use of topical dexpanthenol-containing formulations have therefore been pursued: as skin moisturizer/skin barrier restorer and as facilitator of wound healing. This 70th anniversary paper reviews studies with topical dexpanthenol in skin conditions where it is most frequently used. Although discovered decades ago, the exact mechanisms of action of dexpanthenol have not been fully elucidated yet. With the adoption of new technologies, new light has been shed on dexpanthenol’s mode of action at the molecular level. It appears that dexpanthenol increases the mobility of stratum corneum molecular components which are important for barrier function and modulates the expression of genes important for wound healing. This review will update readers on recent advances in this field.

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Urea: a comprehensive review of the clinical literature

Introduction: Urea is an organic compound that has been used clinically for dermatological diseases for more than a century. Urea is a potent emollient and keratolytic agent, making urea an effective monotherapy for conditions associated with dry and scaly skin. A systematic review of the literature is needed to provide clinicians with evidence-based applications of urea in the treatment of dermatological diseases.

Methods: A PubMed search was conducted using the term “urea” combined with “skin,” “ichthyosis,” “psoriasis,” “xerosis,” “emollient,” “onychomycosis,” “dermatitis,” and “avulsion.” A total of 81 publications met inclusion criteria and were evaluated. Treatment indication(s), test agents, number of subjects, treatment protocols, results, and side effects were recorded.

Results: Effective treatment with urea has been reported for the following conditions: ichthyosis, xerosis, atopic dermatitis/eczema, contact dermatitis, radiation induced dermatitis, psoriasis/seborrheic dermatitis, onychomycosis, tinea pedis, keratosis, pruritus, and dystrophic nails. Furthermore, urea has been used with other medications as a penetration enhancing agent. Mild irritation is the most common adverse event, proving urea to be a safe and tolerable topical drug without systemic toxicity.

Discussion/Conclusion: Urea is a safe, effective dermatologic therapy with wide-ranging clinical utility and minimal, non-systemic side effects. In order to optimize patient care, dermatologists should be well informed with regards to urea’s indications and efficacy.

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Aloe Vera: A Short Review

Aloe vera is a natural product that is now a day frequently used in the field of cosmetology. Though there are various indications for its use, controlled trials are needed to determine its real efficacy. The aloe vera plant, its properties, mechanism of action and clinical uses are briefly reviewed in this article.

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Formulation and in vivo evaluation for anti-aging effects of an emulsion containing basil extract using non-invasive biophysiucal techniques

Background and the purpose of study: Skin aging is a complex process induced by constant exposure to ultraviolet (UV) irradiation and damages human skin. UV generates reactive oxygen species leading to collagen deficiency and eventually skin wrinkling. Basil contains a number of phenolics and favonoids which possess antioxidant properties. The aim of this study was to formulate and investigate the antiaging potential of a cream containing Basil extract.

Methods: A single blinded study was conducted using non-invasive methods. Formulation containing 3% of the concentrated extract of Basil was developed by entrapping in the inner aqueous phase of w/o emulsion and base contained no extract. Both creams were stored at different storage conditions of 8°C, 25°C, 40°C and 40°C+ 75% relative humidity to predict their stabilities. The formulation and base were evaluated for their effects on various skin parameters i.e., moisture and trans epidermal water loss (TEWL), volume, energy and surface evaluation of the living skin (SELS).

Results: Significant effects (p≤0.05) were observed for both creams in the case of TEWL. The base showed insignificant (p≤0.05) while formulation showed significant effects on skin moisture. Volume, SELS SEr (skin roughness), SEsc (skin scaliness), SEsm (skin smoothness), SEw (skin wrinkles) parameter showed significant decline while texture parameter of ‘Energy’ showed significant increase.

Conclusion: The results statistically indicated that the active formulation containg extract of Basil exert antiaging effects when applied topically.

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Research Communication: Topical treatment with coenzyme Q10-containing formulas improves skn’s Q10 level and provides antioxidative effects

Ubiquinone (coenzyme Q10, Q10) represents an endogenously synthesized lipid-soluble antioxidant which is crucial for cellular energy production but is diminished with age and under the influence of external stress factors in human skin. Here, it is shown that topical Q10 treatment is beneficial with regard to effective Q10 replenishment, augmentation of cellular energy metabolism, and antioxidant effects. Application of Q10-containing formulas significantly increased the levels of this quinone on the skin surface. In the deeper layers of the epidermis the ubiquinone level was significantly augmented indicating effective supplementation. Concurrent elevation of ubiquinol levels suggested metabolic transformation of ubiquinone resulting from increased energy metabolism. Incubation of cultured human keratinocytes with Q10 concentrations equivalent to treated skin showed a significant augmentation of energy metabolism. Moreover, the results demonstrated that stressed skin benefits from the topical Q10 treatment by reduction of free radicals and an increase in antioxidant capacity

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Antiaging efficacy of melatonin-based day and night creams: a randomized, split-face assessor-blinded proof-of-concept trial

Background: Skin is a complete and independent melatoninergic system. At the skin level, melatonin (Mel) acts as a relevant antioxidant and cytoprotective substance. Topical application of Mel is considered meaningful, since it can easily penetrate the stratum corneum. Exogenous Mel can be expected to represent a potent antioxidative defense system against skin aging mechanisms. Day and night creams containing Mel, carried in lipospheres (MelatosphereTM), have been developed (Nutriage SPF 30 day cream and Nutriage night cream).

Study aim: The aim of this study was to evaluate the efficacy of a Mel-based cream as antiaging treatment.

Subjects and methods: In a randomized, split-face, assessor-blinded, prospective 3-month study, 22 women (mean age 55 years) with moderate–severe skin aging were enrolled (clinical trial registration number: NCT03276897). Study products were applied in the morning (Nutriage day cream) and evening (Nutriage night cream) on the right or left side of the face. Primary outcomes were: 1) clinical evaluation of wrinkles’ grade (crow’s feet and nasolabial folds), surface microrelief, skin tonicity (resistance to pinching and traction, recovery after pinching) and skin dryness and 2) instrumental evaluation of skin roughness and 3D photographic documentation (Vectra H1 images system). Assessments of both clinical and instrumental evaluations were performed at baseline and after 1, 2 and 3 months of treatment by an investigator unaware of treatment allocation.

Results: All the subjects completed the study. Crow’s feet was reduced significantly (p=0.05) by –15% with the creams in comparison with the non-treated side after 3 months. At the end of the study, surface microrelief (–26.5%), skin profilometry (–13%), skin tonicity (+30%) and skin dryness (–59.5%) significantly improved with active treatment. Both products were well tolerated.

Conclusion: In women with skin aging, Mel-based creams improved significantly skin tonicity and skin hydration with a significant reduction in skin roughness, supporting the skin antiaging effect of this molecule applied topically.

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