# US 2010/0168035 A1 · Subcutaneous implants containing a degradation-resistant polylactide polymer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2010/0168035 A1 - Document ID: US20100168035A1 - Status: Published application - Kind: A1 - Application number: 12/293,758 - Filed: 2007-03-20 - Published: 2010-07-01 - Earliest claimed: 2006-03-21 - Assignees: Hexal AG - Inventors: Anna Sendl-Lang; Kai-Thomas Kramer; Gregor Schütz - Web page: https://patentgrep.com/patent/US20100168035A1 ## CPC - A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)} - A61P 5/06: of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH - A61P 13/08: of the prostate - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 35/00: Antineoplastic agents - A61K 9/204: {Polyesters, e.g. poly(lactide-co-glycolide)} - 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 refers to compositions comprising a LH-RH-analogue and/or pharmaceutically acceptable salts thereof in a low-dose and a degradation-resistant polylactide suitable for the preparation of subcutaneous implants. Sterilisation of the polylactide via gamma-radiation as well as temperature stress result in a negligible decomposition of less than 1000 Dalton. ## Claims ### Claim 1 A monolithic implant comprising; (i) a luteinizing hormone releasing hormone analogue or a pharmaceutically acceptable salt thereof in an amount of less than 25% per weight of the total composition; and (ii) a homogenous polylactide polymer that is resistant to degradation caused by gamma-radiation and/or temperature stress, wherein the degradation-resistant polylactide polymer shows a degree of decomposition of less than 1000 Dalton relative to the weight-average molecular weight of the polymer after gamma-irradiation is performed with an irradiation dose of between about 25 and 40 kGy of ionizing gamma-radiation and/or wherein the degradation-resistant polylactide polymer shows a degree of decomposition of less than 1000 Dalton relative to the weight-average molecular weight of the polymer after temperature stress, at a temperature of about 30° C. over a period of at least 24 months. ### Claim 2 (depends on 1) The monolithic implant of claim 1, wherein the luteinizing hormone releasing hormone analogue is selected from the group consisting of: Leuprorelin, Buserelin, Goserelin, Triptorelin, Nafarelin, Gonadorelin, Cetrorelix, Ganirelix and pharmaceutically acceptable salts thereof. ### Claim 3 (depends on 2) The monolithic implant of claim 2, wherein the luteinizing hormone releasing hormone analogue is Leuprorelin. ### Claim 4 (depends on 2) The monolithic implant of claim 2, wherein the luteinizing hormone releasing hormone analogue is Goserelin. ### Claim 5 (depends on 1) The monolithic implant of claim 1, wherein the amount of the luteinizing hormone releasing hormone analogue is from 15 to 24%, more preferably from 18 to 23% by weight based upon the total weight of the implant. ### Claim 6 (depends on 1) The monolithic implant of claim 1, wherein the degradation-resistant polylactide polymer has a weight-average molecular weight of 4800 to 8600 Dalton, preferably of 5100 to 7800 Dalton and more preferably of 6700 to 7500 Dalton. ### Claim 7 (depends on 1) The monolithic implant of claim 1, wherein the degradation-resistant polylactide polymer has polydispersity index of about 1.2 to 2.2. ### Claim 8 (depends on 1) The monolithic implant of claim 1, wherein the degradation-resistant polylactide polymer has an inherent viscosity, measured in chloroform at a concentration of 0.1 g/dl at 25° C., between about 0.10 to 0.40 dl/g. ### Claim 9 (depends on 1) The monolithic implant of claim 1, wherein the degradation-resistant polylactide polymer has an acid number of more than 10 mg KOH per gram polylactide. ### Claim 10 (depends on 1) The monolithic implant of claim 1, wherein the degradation-resistant polylactide polymer is comprised of at least 5% by weight of polymers having molecular weights of 2700 Dalton or less. ### Claim 11 (depends on 1) The monolithic implant of claim 1, wherein the monolithic implant continuously releases the luteinizing hormone releasing hormone analogue or a pharmaceutically acceptable salt thereof over a period of at least three months when placed in an aqueous physiological-type environment. ### Claim 12 (depends on 7) The monolithic implant of claim 7, wherein the degradation resistant polylactide polymer has polydispersity index of about 1.4 to 1.8 ### Claim 13 (depends on 8) The monolithic implant of claim 8, wherein the degradation resistant polylactide polymer has an inherent viscosity between about 0.12 to 0.36 dl/g. ### Claim 14 (depends on 8) The monolithic implant of claim 8, wherein the degradation resistant polylactide polymer has an inherent viscosity between about 0.16 to 0.24 dl/g. ### Claim 15 (depends on 10) The monolithic implant of claim 10, wherein the degradation-resistant polylactide polymer is comprised of at least 6% by weight of polymers having molecular weights of 2700 Dalton or less. ### Claim 16 (depends on 15) The monolithic implant of claim 15, wherein the degradation-resistant polylactide polymer is comprised of at least 8% by weight of polymers having molecular weights of 2700 Dalton or less. ### Claim 17 (depends on 11) The monolithic implant of claim 11, wherein the monolithic implant continuously releases the luteinizing hormone releasing hormone analogue or a pharmaceutically acceptable salt thereof over a period of at least three four months when placed in an aqueous physiological-type environment. ### Claim 18 (depends on 11) The monolithic implant of claim 11, wherein the physiological-type environment is that of a mammal. ### Claim 19 (depends on 18) The monolithic implant of claim 18, wherein the mammal is a human.