# US 11,439,598 B2 · Synthetic progestogens and pharmaceutical compositions comprising the same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,439,598 B2 - Document ID: US11439598B2 - Status: Granted - Kind: B2 - Application number: 17/711,966 - Filed: 2022-04-01 - Published: 2022-07-14 - Granted: 2022-09-13 - Earliest claimed: 2010-07-28 - Assignees: Laboratorios Leon Farma SA - Applicants: Laboratorios Leon Farma SA - Inventors: Philippe Perrin; Jose Luis Velada; Dominique Drouin - Web page: https://patentgrep.com/patent/US11439598B2 ## CPC - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/1688: {resulting in pure drug agglomerate optionally containing up to 5% of excipient} - A61K 9/2009: {Inorganic compounds} - 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 9/2806: {Coating materials} - A61K 31/567: substituted in position 17 alpha, e.g. mestranol, norethandrolone - A61K 31/585: containing lactone rings, e.g. oxandrolone, bufalin - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - A61K 47/38: Cellulose; Derivatives thereof - A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/4816: {Wall or shell material} - 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) ## Abstract Described herein are synthetic progestogens, such as 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone, as well as pharmaceutical compositions comprising the same. Also described are methods of use. ## Claims ### Claim 1 A pharmaceutical composition comprising: 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone in the form of particles that have a surface area ranging from about 2000 cm2/g to about 8500 cm2/g, wherein the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone is present in an amount ranging from 2 milligrams (mg) to 6 mg; and one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition does not comprise estrogen; and wherein the pharmaceutical composition is formulated such that, (1) when orally administered to a patient under fasting conditions, the pharmaceutical composition provides a pharmacokinetic profile for the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone comprising: (i) a mean Tmax ranging from 2.2 hours to 6 hours; and (ii) a mean Cmax of less than 30 ng/ml; and (no more than 50% of the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone initially present in the pharmaceutical composition is dissolved within 30 minutes if subjected to an in vitro dissolution test according to the USP XXIII Paddle Method. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the one or more pharmaceutically acceptable excipients comprises a filler. ### Claim 3 (depends on 2) The pharmaceutical composition of claim 2, wherein the filler comprises lactose anhydrous, microcrystalline cellulose, starch, pregelatinized starch, modified starch, dibasic calcium phosphate dihydrate, calcium sulfate trihydrate, calcium sulfate dihydrate, calcium carbonate, lactose, dextrose, sucrose, mannitol, sorbitol, or a combination thereof. ### Claim 4 (depends on 1) The pharmaceutical composition of claim 1, wherein the one or more pharmaceutically acceptable excipients comprises a lubricant. ### Claim 5 (depends on 4) The pharmaceutical composition of claim 4, wherein the lubricant comprises magnesium stearate, calcium stearate, zinc stearate, talc, propylene glycol, PEG, stearic acid, vegetable oil, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, mineral oil polyoxyethylene monostearate, or a combination thereof. ### Claim 6 (depends on 1) The pharmaceutical composition of claim 1, wherein the one or more pharmaceutically acceptable excipients comprises a binder. ### Claim 7 (depends on 6) The pharmaceutical composition of claim 6, wherein the binder comprises a starch, a gum, microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, polyvinyl pyrrolidone, or a combination thereof. ### Claim 8 (depends on 7) The pharmaceutical composition of claim 7, wherein the starch comprises potato starch, wheat starch, corn starch, or a combination thereof. ### Claim 9 (depends on 7) The pharmaceutical composition of claim 7, wherein the gum comprises gum tragacanth, acacia gum, gelatin, or a combination thereof. ### Claim 10 (depends on 1) The pharmaceutical composition of claim 1, wherein the one or more pharmaceutically acceptable excipients comprises a glidant. ### Claim 11 (depends on 10) The pharmaceutical composition of claim 10, wherein the glidant comprises silicon dioxide, magnesium trisilicate, powdered cellulose, starch, talc, tribasic calcium phosphate, or a combination thereof. ### Claim 12 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated as a tablet or a capsule. ### Claim 13 (depends on 12) The pharmaceutical composition of claim 12, wherein the pharmaceutical composition further comprises a coating. ### Claim 14 (depends on 13) The pharmaceutical composition of claim 13, wherein the coating comprises hydroxypropylmethyl cellulose, hydroxypropyl cellulose, ethyl cellulose, or a combination thereof. ### Claim 15 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated such that at least 55% of the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone initially present in the pharmaceutical composition is dissolved within 4 hours if subjected to the in vitro dissolution test according to the USP XXIII Paddle Method. ### Claim 16 (depends on 1) The pharmaceutical composition of claim 1, wherein the amount of the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone present ranges from 3.0 mg to 3.5 mg. ### Claim 17 (depends on 1) The pharmaceutical composition of claim 1, wherein the amount of the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone present is about 3.5 mg. ### Claim 18 (depends on 1) The pharmaceutical composition of claim 1, wherein the amount of the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone present is about 4.0 mg. ### Claim 19 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmacokinetic profile for the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone further comprises an AUC0h−tlast of at least 350 ng*h/ml. ### Claim 20 (depends on 1) The pharmaceutical composition of claim 1, wherein the pharmacokinetic profile for the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone further comprises an AUC0h−tlast of at least 300 ng*h/ml. ### Claim 21 (depends on 1) The pharmaceutical composition of claim 1, wherein the surface area ranges from 2000 cm2/g to 8500 cm2/g. ### Claim 22 (depends on 15) The pharmaceutical composition of claim 15, wherein the surface area ranges from 2000 cm2/g to 8500 cm2/g. ### Claim 23 (depends on 19) The pharmaceutical composition of claim 19, wherein the surface area ranges from 2000 cm2/g to 8500 cm2/g. ### Claim 24 (depends on 20) The pharmaceutical composition of claim 20, wherein the surface area ranges from 2000 cm2/g to 8500 cm2/g. ### Claim 25 (depends on 21) The pharmaceutical composition of claim 21, wherein the amount of the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone present ranges from 3.0 mg to 4.5 mg. ### Claim 26 (depends on 22) The pharmaceutical composition of claim 22, wherein the amount of the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone present ranges from 3.0 mg to 4.5 mg. ### Claim 27 (depends on 23) The pharmaceutical composition of claim 23, wherein the amount of the 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone present ranges from 3.0 mg to 4.5 mg.