Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-04-12
1998-08-11
Geist, Gary
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514317, 514375, 514415, 514411, 514427, 514428, 514450, 514532, 514533, 514539, 514545, 514568, 514569, 514886, 514887, 554104, 554110, 554 63, 548440, 548486, 548539, 548500, 548578, 546192, 544 90, A01N 4338
Patent
active
057927863
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to therapeutic conjugates which comprise a therapeutic compound bound to one to three acyl groups derived from fatty acids and to methods involving the use of these compounds. In particular the present invention relates to nonsteroidal anti-inflammatory compounds bound to one to three acyl derivatives of fatty acids.
BACKGROUND OF THE INVENTION
Among the most commonly used therapeutic agents are the nonsteroidal anti-inflammatory drugs. These are typically broken into three major groups:
Of particular interest in the present invention are the nonsteroidal anti-inflammatory agents which include a carboxylic acid group such as salicylates. Of these nonsteroidal anti-inflammatory drugs the most commonly used compounds are acetylsalicylic acid (aspirin), ibuprofen and indomethacin.
The present inventors have now discovered that the nonsteroidal anti-inflammatory drugs and other therapeutic compounds can be linked to one to three fatty acids. These new compounds are believed to improve the transdermal delivery, transdermal uptake, half-life and/or other modes of delivery of these nonsteroidal anti-inflammatory and other therapeutic agents. Further, it is believed that these novel compounds will aid in the oral, internasal and intraocular delivery of the nonsteroidal anti-inflammatory drugs and other therapeutic agents.
SUMMARY OF THE INVENTION
Accordingly, in a first aspect the present invention consists in a compound of the following formula: ##STR1## in which X is a therapeutic compound hydrogen, methyl, ethyl, hydroxyl or an acyl group derived from a fatty acid (saturated or unsaturated) with the proviso that at least one of R.sub.1, R.sub.2 and R.sub.3 is an acyl group derived from a fatty acid.
In a second aspect the present invention consists in a compound of the following formula: R.sub.4 is an acyl group derived from a fatty acid.
In a third aspect the present invention consists in a method of prolonging the activity of a nonsteroidal anti-inflammatory compound comprising administering the compound in the form ##STR2## in which X is the nonsteroidal anti-inflammatory compound hydrogen, methyl, ethyl, hydroxyl or an acyl group derived from a fatty acid with the proviso that at least one of R.sub.1, R.sub.2 and R.sub.3 is an acyl group derived from a fatty acid.
In a fourth aspect the present invention consists in a method of prolonging the activity of a nonsteroidal anti-inflammatory compound comprising administering the compound in the form: R.sub.4 is an acyl group derived from a fatty acid.
In a fifth aspect the present invention consists in a method of treating burns comprising administering a compound of the formula: ##STR3## in which X is ibuprofen Y is absent or is one or two amino acids or a peptide or spacer group hydrogen, methyl, ethyl, hydroxyl or an acyl group derived from a fatty acid with the proviso that at least one of R.sub.1, R.sub.2 and R.sub.3 is an acyl group derived from a fatty acid.
In a sixth aspect the present invention consists in a method of treating burns comprising administering a compound of the formula: R.sub.4 is an acyl group derived from a fatty acid.
As will be recognised by persons skilled in the art, the compound of the first aspect of the present invention consists of a therapeutic compound linked, optionally via an amino acid(s) to a tromethamine derivative to which is linked an acyl group derived from a fatty acid(s). Similarly, the compound of the second aspect can be recognised as a therapeutic agent linked, optionally via an amino acid(s) to an ethanolamine derivative to which is linked an acyl group derived from a fatty acid.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In preferred embodiments of the present invention the therapeutic compound is a nonsteroidal anti-inflammatory compound which preferably includes a carboxylic acid group.
The nonsteroidal anti-inflammatory compound may be selected from a wide range of such known compounds including salicylate, acetylsalicylate, salsalate, diflunisal, f
REFERENCES:
patent: 3686238 (1972-08-01), Zaffaroni
Reeve, Vivienne E., et al: "Lack of Correlation Between Suppression of Contace Hypersensitivity by UV Radiation and Photosiomerization of Epidermal Urocanic Acid in the Hairless Mouse", Photochemistry and Photobiology, vol. 60, No. 3, pp. 268-273, 1994.
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Kaidrey Kays, H., et al: "The Influence of Corticosteroids and Topical Indomethacin of Sunburn Erythema", The Journal of Investigative Dermatology, vol. 66, No. 3, 1976.
Snyder, Diane Sekura: "Cutaneous Effects of Topical Indomethacin, an Inhibitor of Prostaglandin Synthesis, on UV-Damaged Skin", The Journal of Investigative Dermatology, vol. 64, pp. 322-325, 1975.
William, Linda P., et al: "Molecular and Channel Forming Characteristics of Gramicidin K's: A Family of Naturally Occurring Acylated Gramicidins", Biochemistry, vol. 31, No. 32, 1992.
Bissett, D.L., et al: "Photoprotective Effect of Topical Anti-Flammatory Agents Against Ultraviolet Radiation-Induced Chronic Skin Damage in the Hairless Mouse", pp. 153-158, 1989.
Summers, Terry, Derwent Publications Ltd.
Bender Veronika Judith
Reilly Wayne Gerrard
Whittaker Robert George
Carr Deborah D.
Commonwealth Scientific and Industrial Research Organisation
Geist Gary
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