# US 10,478,470 B2 · Pharmaceutical composition containing leuprolide and having both immediate and sustained release properties > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,478,470 B2 - Document ID: US10478470B2 - Status: Granted - Kind: B2 - Application number: 15/417,348 - Filed: 2017-01-27 - Published: 2017-07-13 - Granted: 2019-11-19 - Earliest claimed: 2014-07-28 - Assignees: SK Chemicals Co., Ltd. - Applicants: SK Chemicals Co., Ltd. - Inventors: Hong Kee Kim; Kyu Ho Lee; Seok Hyun Hong; Yong-kyu Kwak; Ho Chul Shin; Hun-Teak Kim - Web page: https://patentgrep.com/patent/US10478470B2 ## CPC - A61K 38/09: Luteinising hormone-releasing hormone [LHRH] {, i.e. Gonadotropin-releasing hormone [GnRH]}; Related peptides - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - 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 9/5031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)} - A61K 31/409: having four such rings, e.g. porphine derivatives, bilirubin, biliverdine (hemin, hematin A61K31/555) - A61K 31/445: Non condensed piperidines, e.g. piperocaine - 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 The present invention relates to a pharmaceutical composition containing leuprolide acetate and having both immediate and sustained release properties and, more specifically, to a pharmaceutical composition in which, on the basis of the total weight of active ingredients, leuprolide as an immediate release preparation is contained in 0.001 wt % to 25 wt %; and leuprolide contained in microspheres of a sustained release preparation is contained in 75 wt % to 99.999 wt %. The pharmaceutical composition of the present invention is characterized by satisfying both a drug immediate release property so as to realize the prompt exposure to a sufficient amount of drug at the early stage for expression of medicinal effects and a drug sustained release property for four weeks or longer, and the pharmaceutical composition is effective in the prevention and treatment of sex hormone-dependent positive or malignant diseases. ## Claims ### Claim 1 A method for preparing a pharmaceutical composition, the method comprising the steps of: (a) preparing an immediate release part comprising leuprolide as a first active ingredient; (b) preparing a sustained release part comprising leuprolide contained in a microsphere as a second active ingredient, wherein the microsphere is prepared by the steps of: (i) mixing an inner aqueous phase (W1) containing leuprolide, a thickener and an aqueous solvent with an oil phase (O) containing a polymer and a fat-soluble solvent to obtain a W1/O emulsion; (ii) dispersing the W1/O emulsion of step (i) in a polyvinyl alcohol aqueous solution (W2) to obtain a W1/O/W2 emulsion; and (iii) drying and recovering the W1/O/W2 emulsion prepared in step (ii); and (c) mixing the immediate release part and the sustained release part in a pharmaceutically acceptable carrier to form a pharmaceutical composition, wherein the immediate release part comprises 0.1% to 20% of a total amount of leuprolide in the pharmaceutical composition and wherein the microsphere of the sustained release part comprises 80% to 99.9% of the total amount of leuprolide in the pharmaceutical composition; and wherein the ratio of leuprolide in the immediate release part to leuprolide in the microsphere of the sustained release part is determined to achieve both immediate and sustained release properties. ### Claim 2 (depends on 1) The method of claim 1, wherein Time to Peak Plasma Concentration (Tmax) of the composition is 50 to 70 minutes. ### Claim 3 (depends on 1) The method of claim 1, wherein the duration of action of the active ingredients in the composition is four weeks or longer. ### Claim 4 (depends on 1) The method of claim 1, wherein the thickener is selected from the group consisting of gelatin, albumin, pectin, agar, cellulose, dextrin, xanthan gum and mixtures thereof. ### Claim 5 (depends on 1) The method of claim 1, wherein the polyvinyl alcohol aqueous solution of step (ii) contains 0.01 to 7% by weight of an osmotic pressure regulator, on the basis of a total weight of the composition. ### Claim 6 (depends on 5) The method of claim 5, wherein the osmotic pressure regulator is selected from the group consisting of pentahydric alcohol, hexahydric alcohol, water-soluble monohydric alcohol, water-soluble monosaccharide, water-soluble disaccharide, water-soluble oligosaccharide or derivatives thereof, and water-soluble amino acid.