Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1997-04-21
1998-08-11
Kumar, Shailendra
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
514844, 554 35, 554 61, A61K 3120, C07C23309
Patent
active
057927944
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 PCT/BA96/03848, filled Sep. 2, 1996.
FIELD OF THE INVENTION
The present invention relates to new compounds namely active derivatives of sphingoid bases. Specifically, the invention relates to retinoylamide based derivatives of sphingoid bases. The present invention describes a method for obtaining these compounds. The invention also relates to the use of these compounds in compositions for topical use.
BACKGROUND OF THE INVENTION
Vitamin A and its derivatives ("retinoids") have been widely used in cosmeticology and dermatology over the past two decades. According to the USP official monograph, the retinoids comprise retinol (vitamin A alcohol) or its esters, the corresponding aldehyde retinal, as well as the free acid retinoic acid, also called vitamin A acid or tretinoin. The role of retinoids in regulation of skin development seems best satisfied by retinoic acid. Thus, activity of retinol, retinal and other vitamin A derivatives such as retinyl-palmitate or -acetate may depend on their conversion to retinoic acid. This conversion depends on the enzymatic activity (e.g. ester cleavage and oxidation) present in the skin and it has been demonstrated that skin preparations can indeed convert retinol to retinoic acid (B. Idson, Cosm. & Toil. (1993), 108, pp.79-88).
Numerous studies have shown a broad range of physiological responses upon retinoid treatment. In general terms, a retinoid applied topically can be regarded as an agent which stimulates the skin both mitotically and metabolically. These effects include among others (Kretz. A., SOFW (1993), 119, 21-24): thickening of the epidermis.
Specifically, retinoic acid containing topical preparations have been developed for the treatment of: Dermatol., 15, pp. 870-877!. al., (1986), J. Am. Acad. Dermatol., 15, pp. 836-859!.
However, the use of retinoids as such, especially retinoic acid, has Dermatol. (1990), 23, pp. 629-637! oxidation, light and UV-radiation. This is the so-called retinoid reaction (often called retinoid dermatitis) and is characterised by redness, dryness and scaling of the skin.
It is known that derivatisation sometimes can eliminate these drawbacks. Vitamin A alcohol (retinol) has been successfully derivatised into e.g. retinyl-acetate and retinyl-palmitate, both of which have improved properties as compared to the alcohol in that they have a reduced instability and irritation-potential. For example, it is known that the vitamin A alcohol is much less stable against heat and light than both these derivatives are preferably used in cosmetic and pharmaceutical preparations.
However, acetate and palmitate which are used for the derivatisation have no additional skin-advantageous properties. In addition, the in situ formation of active retinoic acid from acetate or palmitate derivatives takes two (enzymatic) conversions, i.e. hydrolysis of the ester bond and oxidation of the free retinol into retinoic acid.
SUMMARY OF THE INVENTION
The present invention relates to new compounds namely active derivatives of sphingoid bases. Specifically, the invention relates to retinoylamide based derivatives of sphingoid bases.
The derivatives consist of a sphingoid base in an amide linkage to retinoic acid or to an analogue of retinoic acid. The sphingoid bases are preferably selected from the group comprising sphingosines, phytosphingosines and sphinganines.
The invention further provides a method for preparing these compounds, wherein the retinoic acid or analogue is chemically coupled either as such or as an activated acid to the sphingoid base.
The compounds of the present invention are used in therapy and/or in cosmetics.
Specifically, the compounds are used in the preparation of compositions for topical application.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to new compounds namely active derivatives of sphingoid bases. Specifically, the present invention discloses retinoylamide based derivatives of sphingoid bases.
Sphingoid bases are an important constituent of ceramides. Ceramides form
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patent: 5643899 (1997-07-01), Elias et al.
Vitamins and the Skin, Bernard Idson,Cosmetics and Toiletries, vol. 108, pp. 79-88, Dec. 1993.
Sustained Improvement with Prolonged Topical Tretinoin (Retinoic Acid) for Photoaged Skin, by Charles N. Ellis, et al, Jour. of the Amer. Acad of Dermatology, vol. 23, No. 4, pp. 629-637, Oct. 1990.
Topical Tretinoin for Photoaged Skin, by Albert M. Kligman et al, Jour. of the Amer. Acad. of Dermatology, vol. 15, No. 4, Part 2, pp. 836-859, Oct. 1986.
Selected Therapeutic Applications of Topical Tretinoin, by Andree A. Haas, et al, Jour. of the Amer. Acad. of Dermatology, vol. 15, No. 4, Part 2, pp. 870-877, Oct. 1986.
Robson et. al., J. Lipid Research, vol. 35, pp. 2060-2068, 1994.
Lambers Johannes W. J.
Verweij Jan
Gist-brocades, N.V.
Kumar Shailendra
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