Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2003-04-30
2004-08-10
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S474000
Reexamination Certificate
active
06774114
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Technical Field of the Invention
The present invention relates to the administration, via topical application onto human skin, of immixture of ascorbic acid itself in combination with at least one monosaccharide ester of ascorbic acid and/or at least one metal salt of phosphorylated ascorbic acid, or compositions comprised thereof, for, inter alia, increasing the synthesis of epidermal ceramides.
2. Description of the Prior Art
Human skin consists of two strata or layers, namely, a deep layer, the dermis, and a superficial layer, the epidermis.
The dermis provides the epidermis with a solid support. It is also its feeder component. It consists principally of fibroblasts and an extracellular matrix which is itself principally composed of collagen, elastin and a substance deemed the “ground” substance, these components being synthesized by the fibroblasts. Leukocytes, mastocytes or tissue macrophages are also present therein. The dermis also contains blood vessels and nerve fibers.
The epidermis is exposed to the external environment. Its role entails protecting the body from dehydration and from external factors, whether they are chemical, mechanical, physical or infectious attacks/challenges.
Natural human epidermis is composed mainly of three types of cells which are the keratinocytes, which are highly predominant, the melanocytes and the Langerhans' cells. Each of these cell types contributes, through its specific functions, to the essential role played by the skin in the organism.
The cells constituting the epidermis are delimited by a lipid domain. During differentiation, phospholipids, one role of which is to form the fluid structure of the cell membranes of the living layers of the epidermis, are progressively replaced by a mixture which is predominantly composed of fatty acids, cholesterol and sphingolipids.
These lipids are organized into specific lamellar structures whose integrity depends not only on the quality of the fractions present, but also on their respective proportions. This lamellar structure of the lipids of the lipid domain of the epidermis is responsible for the fluidity and, therefore, suppleness of the skin.
Lipids are also responsible for the “barrier” properties of the epidermis, particularly the stratum corneum.
Epidermal lipids are synthesized principally in the living epidermis. They essentially consist of phospholipids, sphingolipids, cholesterol, free fatty acids, triglycerides, esters of cholesterol and alkanes.
The phospholipids are essential for the constitution of the cell membranes. They play an important role in the mediation of extracellular signals and the formation of free aliphatic chains utilized for the production of energy. They constitute a reservoir of free fatty acids which are necessary for the constitution of sphingolipids.
Sphingolipids (or ceramides) are essential for maintaining the multilamellar structure of the intercorneocyte lipids. They are also essential for water-related exchanges and the “barrier” function of the epidermis.
Cholesterol plays a crucial role in skin hydration and in the “barrier” function of the epidermis.
And free fatty acids play a major role in maintaining the lamellar structure of the lipids of the stratum corneum, and in the constitution of the cell membranes where they are responsible for membrane fluidity and also for physiological processes such as receptor function or enzyme activity.
The essential role played by skin lipids and the importance which their integrity constitutes, are thus manifest.
However, in certain situations, whether in the event of specific pathological conditions (atopic dermatitis), skin aging, actinic aging, dry skin or else a barrier function which is impaired through repeated physical or chemical attacks, the human epidermis exhibits modifications in its lipid synthesis mechanism(s) and/or composition.
To improve the lipid content of the epidermis and consequently to favorably contribute to the suppleness of the skin, two mechanisms of action may be considered. The first is the exogeneous supply of lipid compounds by the topical route. The second entails stimulating the synthesis of endogeneous lipids. It has thus been demonstrated that it was possible to improve the lipid profile of reconstructed epidermes by adding ascorbic acid (vitamin C) to the culture medium (
J. Invest. Dermatol.,
109:348-355, 1997). However, because of its chemical structure (alpha-ketolactone), ascorbic acid is very sensitive to certain environmental parameters such as light, heat and aqueous media, in particular alkaline and/or aerobic media. Because of these problems of stability, it is necessary to use high concentrations of ascorbic acid in order to observe the effect, on the skin, of a composition comprised thereof.
SUMMARY OF THE INVENTION
It has now surprisingly and unexpectedly been determined that the combination or immixture of at least one particular derivative of ascorbic acid with ascorbic acid itself elicits a synergy of action on epidermal lipogenesis and more especially on the synthesis of epidermal ceramides. This synergy allows the use of a lesser amount of ascorbic acid in favor of derivatives thereof which are more stable and therefore easier to formulate into cosmetic or dermatological compositions.
Briefly, then, the present invention features augmenting epidermal lipogenesis (increasing the synthesis of epidermal ceramides) by topically applying onto the skin of an individual subject in need of such treatment, an effective amount of intimate admixture of ascorbic acid itself and at least one compound selected from a monosaccharide ester of ascorbic acid and a metal salt of phosphorylated ascorbic acid.
DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED EMBODIMENTS OF THE INVENTION
More particularly according to the present invention, exemplary monosaccharide esters of ascorbic acid include, in particular, the glycosylated, mannosylated, fructosylated, fucosylated, galactosylated, N-acetylglucosaminated and N-acetylmuramic derivatives of ascorbic acid and mixtures thereof, and more especially ascorbyl 2-glucoside or 2-O-&agr;-D-glucopyranosyl of L-ascorbic acid, or, alternatively, 6-O-&bgr;-D-galactopyranosyl of L-ascorbic acid. The latter compounds as well as processes for the preparation thereof are, in particular, described in EP-A-0,487,404, EP-A-0,425,066 and JP-05,213,736.
In turn, the metal salt of phosphorylated ascorbic acid is advantageously selected from among the ascorbyl phosphates of an alkali metal, the ascorbyl phosphates of an alkaline earth metal and the ascorbyl phosphates of a transition metal. Magnesium ascorbyl phosphate is preferably employed.
In a preferred embodiment, the intimate admixture according to the invention comprises ascorbic acid and a monosaccharide ester of ascorbic acid and a metal salt of phosphorylated ascorbic acid.
The present invention thus also features a regime/regimen for augmenting/increasing the synthesis of epidermal ceramides, comprising topically applying effective amount of synergistic immixture of ascorbic acid/ascorbic acid derivative(s) onto the skin of an individual subject in need of such treatment.
By the expression “epidermal ceramides” according to the present invention are intended both types I to VII ceramides, in particular types IV to VII ceramides, and acylglucosylceramides.
This invention also features compositions comprising the above immixtures, formulated into a physiologically acceptable medium therefor (vehicle, diluent or carrier).
Taking account of the properties of the aforesaid combinations in lipogenesis, the compositions according to the invention are also useful for improving the barrier function of the skin. Such preparations may be for the treatment of certain pathological conditions involving disruption of the barrier function, such as atopic or seborrhoeic dermatitis. Same are also useful for cosmetic purposes, in particular for improving the suppleness of the skin and/or the surface appearance of the skin and/or for combating or preventing skin a
Castiel Isabelle
Ferraris Corinne
Lavalle-Bouchard Armelle
Burns Doane Swecker & Mathis L.L.P.
L'Oreal
Raymond Richard L.
Tucker Zachary C.
LandOfFree
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