Claims for Patent: 8,278,308

Summary for Patent: 8,278,308

Title:	Diketopiperazine salts for drug delivery and related methods
Abstract:	Drug delivery systems have been developed based on the formation of diketopiperazine carboxylate salts and microparticles containing the same. The systems may further comprise a bioactive agent. Related methods for making and using the biologically active agent delivery compositions are also provided. In certain embodiments, the pharmaceutically acceptable salts described can be formed by removal of solvent by methods including distillation, evaporation, spray drying or lyophilization.
Inventor(s):	Leone-Bay; Andrea (Ridgefield, CT), Moye-Sherman; Destardi (Newburgh, NY), Wilson; Bryan R. (Bedford, NY)
Assignee:	MannKind Corporation (Valencia, CA)
Application Number:	12/886,226
Patent Claims:	1. A method for delivery of a biologically active agent comprising: administering to a patient in need of treatment therewith an effective amount of a biologically active agent in the form of microparticles, said microparticles comprising a pharmaceutically acceptable salt of a diketopiperazine and the biologically active agent; wherein said microparticles release said biologically active agent upon administration; and wherein said pharmaceutically acceptable salt of the diketopiperazine has the structure according to Formula 1: ##STR00005## wherein Formula 1 is a diketopiperazine selected from the following compounds: 3,6-di(4-aminobutyl)-2,5-diketopiperazine, 3,6-di(succinyl-4-aminobutyl)-2,5-diketopiperazine, 3,6-di(maleyl-4-aminobutyl)-2,5-diketopiperazine, 3,6-di(citraconyl-4-aminobutyl)-2,5-diketopiperazine, 3,6-di(glutaryl-4-aminobutyl)-2,5-diketopiperazine, 3,6-di(malonyl-4-aminobutyl)-2,5-diketopiperazine, 3,6-di(oxalyl-4-aminobutyl)-2,5-diketopiperazine, and 3,6-di(fumaryl-4-aminobutyl)-2,5-diketopiperazine; and said salt further comprises at least one cation. 2. The method of claim 1 wherein said biologically active agent is selected from the group consisting of hormones, anticoagulants, immunomodulating agents, cytotoxic agents, antibiotics, antivirals, antisense, antigens, antibodies and active fragments and analogues thereof. 3. The method of claim 1 wherein said biologically active agent is selected from the group consisting of insulin, cannabinoids, heparins, calcitonin, felbamate, parathyroid hormone and fragments thereof, growth hormone, erythropoietin, glucagonlike peptide-1, somatotrophin-releasing hormone, follicle stimulating hormone, cromolyn, adiponectin, RNAse, ghrelin, zidovudine, didanosine, tetrahydrocannabinol, atropine, granulocytes colony stimulating factor, lamotrigine, chorionic gonadotropin releasing factor, luteinizing releasing hormone, beta-galactosidase and Argatroban. 4. The method of claim 1 wherein said cation is selected from the group consisting of sodium, potassium, calcium, lithium, triethylamine, butylamine, diethanolamine and triethanolamine. 5. The method of claim 1 wherein R1 or R2 comprise X-4-aminobutyl and wherein X is selected from the group consisting of succinate, glutarate, maleate and fumarate. 6. The method of claim 5 wherein X is fumarate. 7. The method of claim 1 wherein said microparticles have a diameter between about 0.5 microns and about ten microns. 8. The method of claim 1 wherein said microparticles release said biologically active agent upon contact with a biological fluid. 9. The method of claim 1 wherein said delivery is to the pulmonary system. 10. The method of claim 9 wherein said microparticles release said biologically active agent in the pulmonary system. 11. The method of claim 8, wherein the biologically active agent is absorbed into the systemic blood circulation. 12. The method of claim 1 wherein said active agent-containing microparticles are formed by spray drying a solution of said pharmaceutically acceptable salt of a heterocyclic compound and said biologically active agent. 13. The method according to claim 3, wherein said active agent is insulin. 14. The method according to claim 4, wherein said cation is sodium.

Details for Patent 8,278,308

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	01/15/1974		2024-08-23
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	12/27/1984		2024-08-23
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	02/15/1985		2024-08-23
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	02/16/1990		2024-08-23
Bel-mar Laboratories, Inc.	CHORIONIC GONADOTROPIN	chorionic gonadotropin	Injection	017054	03/26/1974		2024-08-23