Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1995-05-11
1999-03-16
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424465, 514970, A61K 920
Patent
active
058826815
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/US94/09945 filed Sep. 2, 1994.
The present invention relates to novel stabilized tablet formulations of substituted 3,5-diene steroidal compounds containing a 3 position electron-withdrawing group and methods of preparing stabilized tablet formulations of substituted 3,5-diene steroidal compounds containing a 3 position electron-withdrawing group. Preferably, this invention relates to novel stabilized tablet formulations of substituted 3,5-diene steroidal compounds containing a 3 position acid group and methods of preparing stabilized tablet formulations of substituted 3,5-diene steroidal compounds containing a 3 position acid group. Preferably, this invention relates to novel stabilized tablet formulations of substituted 3,5-diene steroidal compounds containing a 3 position carboxylic acid group and methods of preparing stabilized tablet formulations of substituted 3,5-diene steroidal compounds containing a 3 position carboxylic acid group. Advantageously, the substituted 3,5-diene steroidal compound for use in the presently invented stabilized tablet formulations and presently invented methods is N-t-butyl-androst-3,5-diene-17.beta.-carboxamide-3-carboxylic acid.
DETAILED DESCRIPTION OF THE INVENTION
Novel substituted 3,5-diene steroidal compounds containing a 3 position electron-withdrawing group have recently been shown to exhibit significant pharmaceutical activity. Specifically, said compounds have been found to inhibit steroid 5-.alpha.-reductase and are thereby useful in the treatment of prostate diseases such as benign prostatic hypertrophy. Stabilized tablet formulations of substituted 3,5-diene steroidal compounds containing a 3 position electron-withdrawing group are advantageous in preparing dosage units for oral administration.
By the term "substituted 3,5-diene steroidal compound" as used herein is meant a compound of the figure ##STR1## wherein W is an electron-withdrawing group; and the C.sub.1 and C.sub.2 positions and the C.sub.8 to C.sub.19 positions are optionally substituted with pharmaceutically acceptable substituents, degrees of unsaturation or a combination of pharmaceutically acceptable substituents and degrees of unsaturation.
The term "electron-withdrawing group" is well known to those of skill in the art and is used herein as its standard meaning which is a functional group that draws electrons to itself more than a hydrogen atom would if it occupied the same position in the molecule, as described in J. March, Advanced Organic Chemistry, third edition, Pub: John Wiley & Sons, Inc. (1985). Preferred electron-withdrawing groups for use in the presently invented stabilized tablet formulations and presently invented methods are: --COOH, --P(O)(OH).sub.2, --PH(O)OH, --SO.sub.3 H, --CHO, --CONHSO.sub.2 R.sup.20 where R.sup.20 is an alkyl group having from 1 to 6 carbon atoms, --CN, --CONH.sub.2 and, where appropriate, esters thereof.
By the term "acid group" as used herein is meant a substituent selected from the group consisting of: --COOH, --P(O)(OH).sub.2, --PH(O)OH and --SO.sub.3 H.
The most preferred electron-withdrawing group for use in the presently invented stabilized tablet formulations and presently invented methods is --COOH.
By the term "fatty acid" as used herein is meant saturated and unsaturated fatty acids of the standard usage wherein the compound contains from about 10 to 22 carbon atoms, preferably decanoic acid, stearic acid, palmitic acid, oleic acid, lauric acid or myristic acid; most preferably, stearic acid.
Preferred substituted 3,5-diene steroidal compounds for use in the presently invented stabilized tablet formulations and presently invented methods include compounds of the Formula I ##STR2## wherein R is a hydrocarbon radical selected from substituted or unsubstituted 1- or 2-adamantyl, 1-, 2- or 7-norbornanyl.
Included within the scope of compounds of Formula I are those wherein the 1- or 2-adamantyl or 1-, 2- or 7-norbornanyl moieties are substituted with one or more of: C.sub.1 -C.sub.4 linear or branched alkyl; nit
REFERENCES:
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patent: 5017568 (1991-05-01), Holt et al.
Faulkner Patrick Gerard
Fisher Mark Warren
Hernandez Carlos Roberto
Sauer Joseph Peter
Dustman Wayne J.
King William T.
Kinzig Charles M.
Page Thurman K.
SmithKline Beecham Corporation
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