Topical application of ceramides

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Cosmetic – antiperspirant – dentifrice

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Details

514627, 514629, 514844, 514847, A61K 748

Patent

active

060013753

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to the topical application of ceramides. Specifically, the present invention discloses specific ceramide-containing compositions which comprise agents to enhance the targeting of a ceramide to the proper site of the skin.


BACKGROUND OF THE INVENTION

Lipid lamellar structures in the intercellular spaces of the stratum corneum are considered to be responsible for the water retaining properties of the stratum corneum (Elias, P. M. (1983), J. Invest. Dermatol. 80, 44-49). It is generally understood that ceramides present within these intercellular lipid lamellae of the stratum corneum have an important structural function in the water impermeability barrier of the skin. The ceramides have shown to be essential in maintaining said barrier (Elias et al., (1991) Adv. Lipid Res. 24, 1-23).
Ceramides are a specific class of lipids belonging to the group of sphingolipids. A sphingolipid is a general term for all lipids containing sphingosine, phytosphingosine or sphinganine as a basic building block. Among the sphingolipids, the ceramides are the most abundant lipids present in the stratum corneum. In mammalian skin, seven predominantly occurring ceramides have been identified. These are mentioned ceramide 1, 2, 3, 4, 5, 6I and 6II (as defined in Wertz et al., (1985) J. Invest. Dermatol. 84, 410-412 and Kerscher et al. (1991), Eur. J. Dermat. 1, 39-43).
It is believed that one of the causes of dry skin is a reduction in the amount of ceramides within the intercellular lipid lamellae. It is therefore desirable to be able successfully to replace these depleted lipids via the topical route.
Ceramides must be able to penetrate the stratum corneum in order to reach the lipid lamellae of the permeability barrier. One of the unsolved problems with the topical application of skin products is to find a suitable way to deliver the active ingredient in sufficient amounts to the place where it must exert its biological activity.
Ceramides are extremely insoluble compounds, a property directly linked to their intrinsic functionality, i.e. the formation of a water-impermeable barrier. As a consequence they are not easy to formulate.
To circumvent these formulation problems, products have been introduced on the market which are not identical, but similar in structure to ceramides. Ceramide-like compounds which are commercially available to date mainly are glycosylceramides (cerebrosides), which are isolated from plant or animal sources, or pseudoceramides, which are no real ceramides but which have an ceramide-analogous structure.
In contrast to real ceramides, glycosylceramides have a relatively high solubility and are easy to formulate. However, it has for instance been shown that glycosylceramides do disturb skin barrier function rather than improving or restoring said function (Holleran et al. (1993) J. Clin. Invest. 91, 1656-1664). Also pseudoceramides, synthetic ceramide-like compounds, often have a higher solubility as compared to ceramides, but these have the disadvantage that they are not biodegradable and consequently can easily accumulate in the skin.
The development of specific formulations which are able to target ceramides to the proper site of the skin is of crucial importance to guarantee efficacy of ceramides.


SUMMARY OF THE INVENTION

The present invention provides ceramide-containing compositions for topical use. The compositions are characterized in that they contain a ceramide and a skin penetration enhancer to target said ceramide to the proper site of the skin, i.e. the stratum corneum.
The skin penetration enhancer preferably is a nonionic or an anionic surfactant.
The nonionic surfactant preferably is an alkoxylated surfactant, more preferably an ethoxylated surfactant. Most preferably, the skin penetration enhancer is selected from the group comprising Ceteareth-2 to Ceteareth-100.
The anionic surfactant preferably is selected from the group of fatty acids or fatty acid derivatives containing one or more carboxylic groups to be neutralized by means of an

REFERENCES:
patent: 5476661 (1995-12-01), Pillai et al.
patent: 5607980 (1997-03-01), McAtee et al.
Elias, P.M., "Epidermal Lipids, Barrier Function, and Desquamation" J Invest Dermatol (1983) 80:44-49.
Elias, P.M., et al., "Structural and Lipid Biochemical Correlates of the Epidermal Permeability Barrier" Adv Lipid Res (1991) 24:1-23.
Holleran, W.M., et al., "Processing of Epidermal Glucosylceramides is Required for Optimal Mammalian Cutaneous Permeability Barrier Function" J Clin Invest (1991) 91:1656-1664.
Kerscher, M., et al., "Skin Ceramides: Structure and Function" Eur J Dermat 1:39-43.
Wertz, P.W., et al., "The Composition of the Ceramides from Human Stratum Corneum and from Comedones" J. Invest Dermatol (1985) 84:410-412.

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