# US 9,040,073 B2 · Silk polymer-based adenosine release: therapeutic potential for epilepsy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,073 B2 - Document ID: US9040073B2 - Status: Granted - Kind: B2 - Application number: 12/991,973 - Filed: 2009-05-15 - Published: 2011-06-23 - Granted: 2015-05-26 - Earliest claimed: 2008-05-15 - Assignees: Trustees of Tufts College - Applicants: Detlev Boison; David L. Kaplan - Inventors: Detlev Boison; David L. Kaplan - Web page: https://patentgrep.com/patent/US9040073B2 ## CPC - A61K 9/0085: {Brain, e.g. brain implants; Spinal cord} - A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) - A61P 25/08: Antiepileptics; Anticonvulsants - A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia - 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 invention provides formulations comprising adenosine in a silk fibroin-based, sustained-release delivery system. The formulations provide sustained, focal release of adenosine at therapeutic levels for the treatment of epilepsy and/or the prevention of epileptogenesis. ## Claims ### Claim 1 A biocompatible, biodegradable, sustained-release implantable pharmaceutical composition comprising adenosine in a silk fibroin-based, sustained-release delivery system, wherein the silk fibroin-based, sustained delivery system comprises adenosine-encapsulating microspheres embedded in a silk fibroin scaffold and wherein the scaffold further comprises adenosine which is not encapsulated in the microspheres, wherein upon implantation said implantable pharmaceutical composition has been shown in reference subjects to release from about 200 ng adenosine per day to about 10 mg adenosine per day, inclusive, for at least eight consecutive days. ### Claim 2 (depends on 1) The biocompatible, biodegradable sustained-release implantable pharmaceutical composition of claim 1, wherein upon implantation said implantable pharmaceutical composition has been shown in reference subjects to release from about 800 ng adenosine per day to about 1100 ng adenosine per day, inclusive, for at least eight consecutive days. ### Claim 3 (depends on 1) The biocompatible, biodegradable sustained-release implantable pharmaceutical composition of claim 1, wherein upon implantation said implantable pharmaceutical composition has been shown in reference subjects to release from about 200 ng adenosine per day to about 5 mg adenosine per day, inclusive, for at least eight consecutive days. ### Claim 4 (depends on 1) The biocompatible, biodegradable sustained-release implantable pharmaceutical composition of claim 1, wherein upon implantation, the implantable composition has been shown in reference subjects to release from about 1 mg adenosine per day to about 10 mg adenosine per day, inclusive, for at least eight consecutive days. ### Claim 5 (depends on 1) The biocompatible, biodegradable sustained-release implantable pharmaceutical composition of claim 1, wherein upon implantation, the implantable composition has been shown in reference subjects to release about 1 mg adenosine per day for a time span of ten days. ### Claim 6 (depends on 1) The biocompatible, biodegradable sustained-release implantable pharmaceutical composition of claim 1, wherein about one-third of the total adenosine in the composition is encapsulated in the microspheres. ### Claim 7 (depends on 1) The biocompatible, biodegradable sustained-release implantable pharmaceutical composition of claim 1, wherein the scaffold comprises one or more silk fibroin coating layers comprising adenosine. ### Claim 8 (depends on 1) The biocompatible, biodegradable sustained-release implantable pharmaceutical composition of claim 1, wherein the scaffold comprises one or more silk fibroin coating layers which comprise no added adenosine. ### Claim 9 A method of treating epilepsy or preventing epileptogenesis in a subject in need thereof comprising administering directly to the brain of the subject a pharmaceutical composition comprising adenosine in a silk fibroin-based, sustained-release delivery system, wherein the silk fibroin-based, sustained delivery system comprises adenosine-encapsulating microspheres embedded in a silk fibroin scaffold and wherein the scaffold further comprises adenosine which is not encapsulated in the microsphere. ### Claim 10 (depends on 9) The method of claim 9, wherein said delivery system has been shown in reference subjects to release from about 50 ng adenosine per day to about 50 mg adenosine per day, inclusive. ### Claim 11 (depends on 10) The method of claim 10, wherein said delivery system has been shown in reference subjects to release from about 200 ng adenosine per day to about 5 mg adenosine per day, inclusive. ### Claim 12 (depends on 10) The method of claim 10, wherein said delivery system has been shown in reference subjects to release at least about 1 mg adenosine per day to about 10 mg adenosine per day, inclusive.