# US 10,500,381 B2 · Drug delivery system > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,500,381 B2 - Document ID: US10500381B2 - Status: Granted - Kind: B2 - Application number: 14/371,848 - Filed: 2013-01-22 - Published: 2014-11-27 - Granted: 2019-12-10 - Earliest claimed: 2012-01-23 - Assignees: Bayer Aktiengesellschaft - Applicants: Bayer Oy - Inventors: Heikki Lyytikäinen; Harri Jukarainen - Web page: https://patentgrep.com/patent/US10500381B2 ## CPC - A61M 31/002: {Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time (artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50)} - 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)} - A61K 9/0036: {Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms} - A61K 9/0039: {Devices retained in the uterus for a prolonged period, e.g. intrauterine devices for contraception} - A61K 9/0092: {Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes} - A61K 47/02: Inorganic compounds - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 15/02: for disorders of the vagina - A61P 15/18: Feminine contraceptives - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - 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 a novel drug delivery system for the controlled release of therapeutically active substances at a predetermined, essentially constant release rate over a prolonged period of time. The delivery system comprises at least one core comprising said therapeutically active substance(s), at least one membrane encasing the core and an intermediary layer of a substantially inert material, wherein the intermediary layer is applied between the core and the membrane or between two membrane layers. ## Claims ### Claim 1 A drug delivery system comprising at least one core comprising Levonorgestrel and at least one membrane encasing the core, wherein the system further comprises an intermediary layer consisting of a substantially inert material and optionally a liquid solvent or silicone oil, wherein the intermediary layer is not covalently bound to the material of the core and is not covalently bound to the material of the at least one membrane and the substantially inert material is selected from the group consisting of silica, and fumed and precipitated silicas to maintain at least substantially constant release of the Levonorgestrel during course of usage with no or diminished initial burst as compared to a delivery system without the intermediary layer, wherein the drug delivery system has a release rate that is relatively constant for from 1 week to 7 years. ### Claim 2 (depends on 1) A drug delivery system according to claim 1, characterized in that the substantially inert material is in a form which is at least one selected from the group consisting of particulate matter, particle, granule, crystal, microscaled crystal, nanoscaled crystal, powder in a solid form, suspended powder, and powder in a gel form. ### Claim 3 (depends on 1) A drug delivery system according to claim 1, characterized in that the intermediary layer of a substantially inert material is applied between the core and the membrane. ### Claim 4 (depends on 1) A drug delivery system according to claim 1, characterized in that the intermediary layer of a substantially inert material is applied between two membrane layers. ### Claim 5 (depends on 1) A drug delivery system according to claim 1, characterized in that the system is a vaginal delivery system, an implant, an intrauterine delivery system, an intracervical delivery system, a helical coil or a spring, wherein the core is at least 20 mm in length. ### Claim 6 (depends on 1) A drug delivery system according to claim 1, further including a coating of an adherent over the core and wherein the substantially inert material covers the coating. ### Claim 7 (depends on 6) A drug delivery system according to claim 6, wherein the adherent is silicone oil. ### Claim 8 (depends on 1) A drug delivery system according to claim 1 wherein the drug delivery system has a release rate that is relatively constant for 21 days. ### Claim 9 (depends on 1) A drug delivery system according to claim 1 wherein the drug delivery system has a release rate that is relatively constant for 3 months. ### Claim 10 (depends on 1) The drug delivery system according to claim 1, wherein the drug delivery system is an intrauterine system; wherein the core is a polymer matrix comprising a first polymer where the one or more therapeutically active substance(s) are dissolved or dispersed; wherein the at least one membrane encasing the core comprises a second polymer; and wherein the first polymer and the second polymer are each a polysiloxane. ### Claim 11 (depends on 1) A drug delivery system according to claim 1, wherein the drug delivery system has a release rate that is relatively constant from 1 week to 12 months. ### Claim 12 (depends on 1) A drug delivery system according to claim 1, wherein the drug delivery system has a release rate that is relatively constant from 1 year to 5 years.