# US 8,772,271 B2 · Micronized tanaproget, compositions, and methods of preparing the same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,772,271 B2 - Document ID: US8772271B2 - Status: Granted - Kind: B2 - Application number: 13/890,523 - Filed: 2013-05-09 - Published: 2013-09-26 - Granted: 2014-07-08 - Earliest claimed: 2005-04-28 - Assignees: Wyeth - Applicants: Wyeth LLC - Inventors: Arwinder S. Nagi; Ramarao Chatlapalli; Shamim Hasan; Mohamed Ghorab; Dhaval Gaglani - Web page: https://patentgrep.com/patent/US8772271B2 ## CPC - A61K 9/16: Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)} - A61K 9/0002: {Galenical forms characterised by the drug release technique; Application systems commanded by energy} - A61K 9/167: {with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface (with further drug-free outer coating A61K9/5073)} - A61K 9/2013: {Organic compounds, e.g. phospholipids, fats} - A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates} - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets} - A61K 31/536: ortho- or peri-condensed with carbocyclic ring systems - A61P 5/00: Drugs for disorders of the endocrine system - A61P 5/34: Gestagens - A61P 5/36: Antigestagens - A61P 13/00: Drugs for disorders of the urinary system - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis - A61P 15/12: for climacteric disorders - A61P 15/18: Feminine contraceptives - A61P 35/00: Antineoplastic agents - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention provides compositions, desirably pharmaceutical compositions, containing micronized tanaproget. The compositions can also contain microcrystalline cellulose, croscarmellose sodium, anhydrous lactose, magnesium stearate, micronized edetate calcium disodium hydrous, and micronized sodium thiosulfate pentahydrate. The compositions are useful in contraception and hormone replacement therapy and in the treatment and/or prevention of uterine myometrial fibroids, benign prostatic hypertrophy, benign and malignant neoplastic disease, dysfunctional bleeding, uterine leiomyomata, endometriosis, polycystic ovary syndrome, and carcinomas and adenocarcinomas of the pituitary, endometrium, kidney, ovary, breast, colon, and prostate and other hormone-dependent tumors, and in the preparation of medicaments useful therefor. Additional uses include stimulation of food intake. ## Claims ### Claim 1 A kit comprising a pharmaceutical composition comprising an intragranulation comprising micronized tanaproget or a pharmaceutically acceptable salt thereof, microcrystalline cellulose, croscarmellose sodium, anhydrous lactose, magnesium stearate, micronized edetate calcium disodium hydrous, and micronized sodium thiosulfate pentahydrate. ### Claim 2 (depends on 1) The kit according to claim 1, wherein said pharmaceutical composition further comprises extragranular croscarmellose sodium and extragranular magnesium stearate. ### Claim 3 (depends on 2) The kit according to claim 2, wherein said extragranular croscarmellose sodium comprises about 2% wt/wt of said pharmaceutical composition. ### Claim 4 (depends on 2) The kit according to claim 2, wherein said extragranular magnesium stearate comprises about 0.19% of said pharmaceutical composition. ### Claim 5 (depends on 1) The kit according to claim 1, wherein the particles of said micronized tanaproget are less than about 10 μm. ### Claim 6 (depends on 1) The kit according to claim 1, wherein the particles of said micronized sodium thiosulfate pentahydrate are less than about 31 μm. ### Claim 7 (depends on 1) The kit according to claim 1, wherein the particles of said micronized sodium edetate calcium disodium hydrous are less than about 35 μm. ### Claim 8 (depends on 1) The kit according to claim 1, wherein said pharmaceutical composition degrades less than about 3% over a period of greater than 1 month at temperatures at or greater than about 25° C. and a relative humidity at or greater than about 60%. ### Claim 9 (depends on 1) The kit according to claim 1, wherein said tanaproget comprises about 0.15% to about 0.50% wt/wt of said pharmaceutical composition. ### Claim 10 (depends on 1) The kit according to claim 1, wherein said tanaproget comprises about 0.15% wt/wt of said pharmaceutical composition. ### Claim 11 (depends on 1) The kit according to claim 1, wherein said tanaproget comprises about 0.23% wt/wt of said pharmaceutical composition. ### Claim 12 (depends on 1) The kit according to claim 1, wherein said tanaproget comprises about 0.31% wt/wt of said pharmaceutical composition. ### Claim 13 (depends on 1) The kit according to claim 1, wherein said tanaproget comprises about 0.5% wt/wt of said pharmaceutical composition. ### Claim 14 (depends on 1) The kit according to claim 1, wherein said intragranular microcrystalline cellulose comprises about 40% wt/wt of said pharmaceutical composition. ### Claim 15 (depends on 1) The kit according to claim 1, wherein said intragranular croscarmellose sodium comprises about 2% wt/wt of said pharmaceutical composition. ### Claim 16 (depends on 1) The kit according to claim 1, wherein said intragranular magnesium stearate comprises about 0.19% wt/wt of said pharmaceutical composition. ### Claim 17 (depends on 1) The kit according to claim 1, wherein said intragranular anhydrous lactose comprises about 54% to about 55% wt/wt of said pharmaceutical composition. ### Claim 18 (depends on 1) The kit according to claim 1, wherein said intragranular micronized edetate calcium disodium hydrous comprises about 0.10% wt/wt of said pharmaceutical composition. ### Claim 19 (depends on 1) The kit according to claim 1, wherein said intragranular micronized sodium thiosulfate pentahydrate comprises about 0.5% wt/wt of said pharmaceutical composition. ### Claim 20 (depends on 1) The kit according to claim 1, wherein the particles of said pharmaceutical composition are less than about 100 μm. ### Claim 21 (depends on 1) The kit according to claim 1, further comprising one or more progestational agent, estrogen, or selective estrogen receptor modulator. ### Claim 22 (depends on 1) The kit according to claim 1, comprising a single phase of a daily dosage of said pharmaceutical composition over a 21-day, 28-day, 30-day, or 31-day cycle. ### Claim 23 (depends on 1) The kit according to claim 1, comprising a single phase of a daily dosage of said pharmaceutical composition over the first 21 days of a 28-day, 30-day, or 31-day cycle. ### Claim 24 (depends on 1) The kit according to claim 1, comprising a single phase of a daily dosage of said pharmaceutical composition over the first 28 days of a 30-day or 31-day cycle. ### Claim 25 (depends on 1) The kit according to claim 1, comprising a single combined phase of a daily dosage of said pharmaceutical composition and a progestational agent; wherein the daily dosage units total 28. ### Claim 26 (depends on 1) The kit according to claim 1, comprising 21 daily dosage units of a single combined phase of said pharmaceutical composition and a progestational agent; wherein the daily dosage units total 28, 30, or 31. ### Claim 27 (depends on 1) The kit according to claim 1, comprising 28 daily dosage units of a single combined phase of said pharmaceutical composition and a progestational agent; wherein the daily dosage units total 30 or 31. ### Claim 28 (depends on 1) The kit according to claim 1, comprising: (i) a first phase of from 14 to 28 daily dosage units of said pharmaceutical composition; (ii) a second phase of from 1 to 11 daily dosage units of a progestational agent; and (iii) daily dosage units of an orally and pharmaceutically acceptable placebo; wherein the daily dosage units total 28. ### Claim 29 (depends on 1) The kit according to claim 1, comprising: (i) a first phase of from 14 to 21 daily dosage units of said pharmaceutical composition; and (ii) a second phase of from 1 to 11 daily dosage units of a progestational agent; and (iii) daily dosage units of an orally and pharmaceutically acceptable placebo; wherein the daily dosage units total 28. ### Claim 30 (depends on 1) The kit according to claim 1, comprising: (i) a first phase of from 18 to 21 daily dosage units of said pharmaceutical composition; and (ii) a second phase of from 1 to 7 daily dose units of a progestational agent; and (iii) daily dosage units of an orally and pharmaceutically acceptable placebo; wherein the daily dosage units total 28. ### Claim 31 (depends on 1) The kit according to claim 1, comprising: (i) a first phase of 21 daily dosage units of said pharmaceutical composition; (ii) a second phase of 3 daily dosage units for days 22 to 24 of a progestational agent; (iii) a third phase of 4 daily dosage units for days 25 to 28 of a pharmaceutically acceptable placebo; wherein the daily dosage units total 28. ### Claim 32 (depends on 1) The kit according to claim 1, comprising: (i) a first phase of from 14 to 21 daily dosage units of a progestational agent equal in progestational activity to about 35 to about 150 μg levonorgestrel; and (ii) a second phase of from 1 to 11 daily dosage units of said pharmaceutical composition; and (iii) daily dosage units of an orally and pharmaceutically acceptable placebo; wherein the daily dosage units total 28. ### Claim 33 (depends on 1) The kit according to claim 1, comprising: (i) a first phase of from 14 to 21 daily dosage units of a progestational agent equal in progestational activity to about 35 to about 100 μg levonorgestrel; and (ii) a second phase of from 1 to 11 daily dosage units of said pharmaceutical composition; and (iii) daily dosage units of an orally and pharmaceutically acceptable placebo; wherein the daily dosage units total 28. ### Claim 34 (depends on 1) The kit according to claim 1, which is designed for treating or preventing benign prostatic hypertrophy, benign neoplastic disease, malignant neoplastic disease, dysfunctional bleeding, uterine leiomyomata, polycystic ovary syndrome, carcinomas, or adenocarcinomas. ### Claim 35 A kit comprising a pharmaceutical composition comprising about 0.15% wt/wt micronized tanaproget or a pharmaceutically acceptable salt thereof, about 40% wt/wt microcrystalline cellulose, about 4% wt/wt croscarmellose sodium, about 54.87% wt/wt anhydrous lactose, about 0.38% wt/wt magnesium stearate, about 0.1% wt/wt micronized edetate calcium disodium hydrous, and about 0.5% wt/wt micronized sodium thiosulfate pentahydrate. ### Claim 36 A kit comprising a pharmaceutical composition comprising about 0.23% wt/wt micronized tanaproget or a pharmaceutically acceptable salt thereof, about 40% wt/wt microcrystalline cellulose, about 4% wt/wt croscarmellose sodium, about 54.79% wt/wt anhydrous lactose, about 0.38% wt/wt magnesium stearate, about 0.1% wt/wt micronized edetate calcium disodium hydrous, and about 0.5% wt/wt micronized sodium thiosulfate pentahydrate. ### Claim 37 A kit comprising a pharmaceutical composition comprising about 0.31% wt/wt micronized tanaproget or a pharmaceutically acceptable salt thereof, about 40% wt/wt microcrystalline cellulose, about 4% wt/wt croscarmellose sodium, about 54.71% wt/wt anhydrous lactose, about 0.38% wt/wt magnesium stearate, about 0.1% wt/wt micronized edetate calcium disodium hydrous, and about 0.5% wt/wt micronized sodium thiosulfate pentahydrate. ### Claim 38 A kit comprising a pharmaceutical composition comprising about 0.46% wt/wt micronized tanaproget or a pharmaceutically acceptable salt thereof, about 40% wt/wt microcrystalline cellulose, about 4% wt/wt croscarmellose sodium, about 54.56% wt/wt anhydrous lactose, about 0.38% wt/wt magnesium stearate, about 0.1% wt/wt micronized edetate calcium disodium hydrous, and about 0.5% wt/wt micronized sodium thiosulfate pentahydrate.