Scientific Support for Diacneal in Skin Rejuvination and Anti-Aging Therapies

Department of Dermatology, University Hospital, Geneva, Switzerland. christian.tran@hcuge.ch

BACKGROUND: Retinoids and alpha-hydroxy acids (AHAs) are major compounds in topical therapy. They exert distinct but potentially complementary activities. However, their association is limited by their respective irritating potential. Recently, the first association between a retinoid and an AHA has been achieved; this formulation (RALGA) associates retinaldehyde (RAL)--a precursor of retinoic acid (RA)--and glycolic acid (GA)--an AHA. OBJECTIVE: To study the pharmacological properties of RALGA. METHODS: The bioavailability of RAL into the skin after topical RALGA was studied by HPLC, and its bioconversion to RA was analysed by measuring the enzyme activity of retinaldehyde dehydrogenase and the RA content in the epidermis and dermis. The retinoid activity of RALGA was studied on the modulation of Hhb4 keratin mRNA on the tail of C57BL/6 mice, and its comedolytic properties on the size and density of dermal cysts and the morphology of sebaceous glands in hairless mice. RESULTS: Epidermal and dermal concentrations of RAL and RA were higher after RALGA treatment, as compared to both RAL 0.1% alone and RA 0.05% alone; this indicates that the presence of GA favours the bioavailability and biotransformation of RAL into RA. The retinoid activity of RALGA (suppression of Hhb4 mRNA keratin) was similar to that of RAL alone, indicating that the presence of GA does not interfere with specific retinoid activity; GA alone had no effect in this test, which confirms the specificity of Hhb4 mRNA keratin modulation for retinoid activity. The diameter and the density of dermal cysts as well as the size of sebaceous glands were significantly decreased by RALGA. CONCLUSION: These observations indicate that the addition of an AHA such as GA [glycolic acid] to a retinoid such as RAL [retinaldehyde] results in a better bioavailability of the retinoid, thus a higher delivery of RA [retinoic acid], which potentiates the biological activities of the retinoid. This combination allows a delivery of high amounts of RA in the skin while preventing the side-effects usually observed with high concentrations of topical RA.

PMID: 15724102 [PubMed - indexed for MEDLINE]

A. Sygros Hospital, University of Athens, Athens, Greece. katsabas@internet.gr

Acne vulgaris affects 3 out of 4 adolescents and usually vanishes at the end of puberty with either no sequelae or mild to moderate sequelae, such as postinflammatory hyperpigmenation (PIH), which may result in psychological and emotional damages. The poor tolerability of the actual treatments (secondary inflammation) is a hindrance to therapy. Retinaldehyde (RAL), a precursor of retinoic acid, has shown depigmenting activity. Glycolic acid (GA) decreases the excess of pigment by a wounding and re-epithelization process. Thus, a synergistic effect was expected from the combination of RAL 0.1% and GA 6% RALGA (Diacneal) in the treatment of acne vulgaris and PIH. Efficacy results of preclinical and clinical trials tend to confirm the expectations for both acne and PIH treatment. A good tolerability was observed. In conclusion, the cosmetic cream Diacneal is a well-tolerated treatment for the prevention and healing of PIH in acne patients.

PMID: 15724107 [PubMed - indexed for MEDLINE]

Clinique de Dermatologie, Geneva University Hospital, Geneva, Switzerland. olivier.sorg@hcuge.ch

Retinoids are natural and synthetic vitamin A derivatives. They are lipophilic molecules and easily penetrate the epidermis. Their biologically active forms can modulate the expression of genes involved in cellular differentiation and proliferation. Retinoic acid (tretinoin), its 13-cis isomer isotretinoin, as well as various synthetic retinoids are used for therapeutic purposes, whereas retinaldehyde, retinol, and retinyl esters, because of their controlled conversion to retinoic acid or their direct receptor-independent biologic action, can be used as cosmeceuticals. These natural retinoic acid precursors are thus expected to be helpful in (i) renewing epidermal cells, (ii) acting as UV filters, (iii) preventing oxidative stress, (iv) controlling cutaneous bacterial flora, and (v) improving skin aging and photoaging. Retinol and retinyl esters are not irritant, whereas demonstrating only a modest clinical efficiency. On the other hand, retinaldehyde, which is fairly well tolerated, seems to be the most efficient cosmeceutical retinoid; it has significant efficiency toward oxidative stress, cutaneous bacterial flora, epidermis renewing, and photoaging.

PMID: 17014484 [PubMed - in process]

Service de Stomatologie Maxillo-Faciale du Prof. J.C. Bertrand, Hopital Pitie-Salpetriere, Paris, France. sylvie.boisnic@ap-hop-paris.fr

BACKGROUND: Retinaldehyde and glycolic acid RALGA (Diacneal) are both effective in the topical treatment of acne. A decrease in the postinflammatory pigmentation has been observed after application of Diacneal during 3 months. AIM: To verify the effect of this association on pigmentation using an original model of surviving human skin. METHODS: Human skin explants were maintained alive in organ culture for 14 days. Diacneal was applied every day. Pigmentation of skin, depending on the transfer of melanosomes from melanocytes to keratinocytes, was visualized histologically by Fontana-Masson staining. The number of melanocytes was determined after the DOPA reaction. RESULTS: A decrease in melanin content was shown after application of Diacneal. The number of melanocytes was not modified. CONCLUSION: These results suggest that RALGA (Diacneal) may be of interest to prevent the postinflammatory pigmentation of acne.

PMID: 15724106 [PubMed - indexed for MEDLINE]

Topical retinoids such as all-trans-retinoic acid (RA), 13-cis-retinoic acid (isotretinoin), retinol, retinaldehyde, tazarotene, and adapalene have been shown to improve dyspigmentation of photodamaged skin including mottling and actinic lentigines. RA monotherapy has also been demonstrated to improve melasma and postinflammatory hypermelanosis. Furthermore, RA in combination with hydroquinone or 4-hydroxyanisole, or azelaic acid increases the potency of depigmenting agents for the treatment of melasma, actinic lentigines, and postinflammatory hypermelanosis. The basic mechanisms underlying these effects are not completely identified. Topical retinoids stimulate the cell turn-over of epidermal keratinocytes and promote a decrease in melanosome transfer and a rapid loss of melanins via epidermopoiesis. Topical retinoids are also involved in the control of cell differentiation. Retinoid-induced changes in the stratum corneum and the permeability barrier may also facilitate the penetration of depigmenting agents in the epidermis and increase their bioavailability, leading to increased depigmentation. In addition, several in vitro studies demonstrate that cis and trans-retinoic acid inhibit UV-B stimulated melanogenesis in term of tyrosinase activity and melanin synthesis. It is likely that topical retinoids modulate epidermal melanin count via a direct action on melanocytes and epidermal keratinocytes.

PMID: 17014483 [PubMed - in process]