The science supporting skinceuticals retinol products

THE SCIENCE SUPPORTING SKINCEUTICALS RETINOL PRODUCTS ABSTRACT technology that largely prevents the degradation of Retinol (vitamin A) and its natural and synthetic retinol due to light and heat exposure.1 The analogs are collectively known as retinoids. difficulties encountered in the 1960s did lead to the Retinoid research has been conducted for nearly a concentration of research activities on retinoic acid century and has yielded comprehensive findings regarding the importance of vitamin A as a consequently, the establishment of retinoid drugs nutrient, as well as the biological activities and for various skin diseases. These medicinal products pharmacological profiles of the various retinoids, are generally classified into different generations of most eminently retinol (ROL) and retinoic acid retinoid development: The first generation (RA). Drugs based on retinoids are now available comprises trans-retinoic acid or tretinoin (Retin- for the treatment of psoriasis, acne and other A®) and 13-cis-retinoic acid or isotretinoin dermatologic conditions related to keratinization. (Accutane®), products effective for the treatment of Medical research indicates that retinoic acid is acne. Etretinate and acitretin (Tegison and beneficial to maintain youthful skin and to repair Soriatane) are second generation retinoid-based damage caused by UV exposure or intrinsic aging. drugs and are used primarily for the treatment of Retinol is converted to retinoic acid once applied to psoriasis. A third generation still in experimental the skin, but is without the prohibitive irritation stage is arotenoids, possibly beneficial in the potential of the latter. Studies show retinol as a application of some cancer therapies.2 Each retinoid viable solution for combating skin aging and has its own profile of pharmacological properties problematic skin when delivered in a stable that determine its usefulness in clinical dermatology or oncology. In addition to existing clinical research, researchers found that retinoids can have a positive effect on intrinsic as well as photoaging Retinol has long been known as an important nutrient involved in a wide variety of functions from embryonic development to cell differentiation and vision. Deficiency of dietary vitamin A results in generalized xerosis, hyperkeratosis and Retinol (natural vitamin A) is obtained from the diet squamous metaplasia of mucous membranes. ROL either directly from foods such as fish oil and liver or is the natural, diet-derived vitamin A, though the indirectly in the form of beta-carotene, which with collective term also includes its metabolites retinal the help of enzymes is then converted to retinol for and retinoic acid. All three are part of a greater membrane transport. Retinol can be converted to family generally referred to as retinoids. Grouped retinoic acid for target cell delivery or converted to under this umbrella are not only the natural retinoids: retinol, retinal, and retinoic acid, but also the many synthetic analogs that have been Retinol binds with specific retinol-binding proteins researched and developed since the significance of (CRBP-I, CRPB II). These proteins facilitate the vitamin A and all retinoids was discovered in the transport inside the cell, and are also believed to protect the molecule from non-specific oxidation. After the enzymatic conversion of the ROL molecule to RA, RA binds to the cellular retinoic acid binding The importance of retinoids in dermatology dates molecule CRABP (CRABP-I, CRABP-II) and is transported from the cytoplasm to the nucleus. From identified epidermal changes as abnormal there, it exerts its effect on the target cells by keratinization in vitamin A deficient animals. These activating the retinoid receptors known as RA observations were followed by numerous studies receptors (RARs) and retinoid X receptors (RXRs). focused on the metabolism and pharmacological These receptors contain domains that bind to specific action of retinoids in the skin. Investigations DNA sequences, RA response elements (RARE), and regarding the effect of topical retinol in the early function to enhance or reduce gene transcription.3, 4 1960s (Kligman, Stuttgen) were unsuccessful due to In human skin and dermal fibroblasts, it is cellular ROL instability. These difficulties have recently retinoic acid binding protein II (CRABP-II) mRNA been overcome by the creation of formulation that is selectively induced by all-trans retinoic acid.5 Note: Of the natural vitamin A compounds prominent agent among retinoids for combating (retinol, retinal, retinoic acid, retinoic ester), only skin aging as well as problematic skin. Factors concentration, stability, encapsulation method, and formulation. Results from various studies show The skin is formed by two basic layers: the retinol, when properly formulated, to be an epidermis, composed of keratinocytes in different effective topical treatment preferred to other stages of growth and differentiation, and the dermis, whose major cellular constituents are fibroblasts, which synthesize the fibrous component of the dermal connective tissue, i.e. collagen and 1 Kligman L, Gans E. Re-emergence of topical elastin fibers, as well as other extracellular matrix retinol in dermatology. J of Dermatological components, such as fibronectin and laminin. Researchers suggest that cutaneous aging results 2 Neumann, Martino. Systemic and topical drugs from the interplay of extrinsic damage by UV for aging skin. Journal of Drugs in Dermatology radiation, intrinsic increases in collagen-degrading matrix metalloproteinases (MMPs) and decreased 3 Roos T, Jugert K, Merk H. Bickers D. Retinoid collagen synthesis. Numerous large-scale, double- metabolism in the skin. Pharmacological Review blinded and placebo-controlled trials have shown the efficacy of topical tretinoin in the treatment of 4 Ross AC. Overview of retinoid metabolism. J photoaging. However, as tretinoin remains a prescription drug, and in addition has a high 5 Elder J. Kang S., Voorhees J. et al. Retinoid irritation potential, over-the-counter products Induction of CRABP II mRNA in Human Dermal mainly use retinol and retinyl palmitate. Fibroblasts. J of Investigative Dermatology 1996; 6 Varani J. et al. Vitamin A antagonizes decreased Researchers believe that retinol plays an important cell growth and elevated collagen-degrading role in countering aging mechanisms described matrix metalloproteinases and stimulates collagen above. A study utilizing human skin samples found accumulation in naturally aged human skin. J of that topical 1% retinol inhibits the increase in Investigative Dermatology 2000; 114: 480-86 metalloproteinases and stimulates collagen 7 Kang S, Fisher G. Voorhees J. et al. Application synthesis in both intrinsically aged and photoaged of retinol to human skin in vivo induces skin.6 Varani et al. also used tissue specimens to epidermal hyperplasia and cellular retinoid show that retinol may be able to restimulate binding proteins characteristic of retinoic acid but fibroblast growth potential, which seems to without measurable retinoic acid levels of decrease with increasing age. Further, Kang et al. irritation. J of Investigative Dermatology 1995; showed that topical retinol does increase epidermal thickness in human skin, but without the irritation of RA.7 The above studies show that concentrations of 1% retinol produced results equivalent to prescription strength retinoic acid. Evidence for the Guttman C. Studies back retinol as photoaging tx. effectiveness and biological activity of the ester form of vitamin A, retinyl palmitate, is sparse and Vahlquist A., What are natural retinoids. no studies address clinically relevant findings in Dermatology 1999; 199 (suppl 1)3-11 skin aging. Further, in mice, retinol stores in the Griffiths CEM. The role of retinoids in the prevention epidermis were partially UVB resistant, while and repair of aged and photoaged skin. Clinical and Experimental Dermatology 2001; 26: 613-18 Retinoids are among the most prescribed and recommended classes of agents in the dermatologic arsenal. Decades of research have led to versatility in use of these products. Studies demonstrating corrective benefits such as cell regeneration, exfoliation, and dermal collagen synthesis suggest an important role for topical retinoids in counteracting the effects of photoaging. Although still in the early stages of research, retinol is a


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