Method of modifying the release profile of sustained release compositions

• US 20040147488A1
• Filed: 01/16/2004
• Published: 07/29/2004
• Est. Priority Date: 04/13/2001
• Status: Active Grant

• Current Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Original Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Inventors: Riley, M. Gary I., Dasch, James R.
• Granted Patent: US 7,074,432 B2
• Time in Patent Office: Days
• US Class Current: 514/102
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/663 Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: 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
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077

Abstract

The present invention relates to a method for the sustained release in vivo of a biologically active agent comprising administering to a subject in need of treatment an effective amount of a sustained release composition comprising a biocompatible polymer having the biologically active agent incorporated therein, and a bisphosphonate wherein the bisphosphonate compound is present in an amount sufficient to modify the release profile of the biologically active agent from the sustained release composition. Pharmaceutical compositions suitable for use in the method of the invention are also disclosed.

Claims

1. A sustained release composition comprising a biocompatible, biodegradable polymer having incorporated therein a bisphosphonate compound of Formula I or a pharmaceutically acceptable salt thereof:

2. The sustained release composition of claim 1, wherein the biocompatible, biodegradable polymer is selected from the group consisting of:

poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, polycarbonates, polyesteramides, polyanydrides, poly(amino acids), polyorthoesters, poly(dioxanone)s, poly(alkylene alkylate)s, copolymers or polyethylene glycol and polyorthoester, biodegradable polyurethane, blends thereof, and copolymers thereof.

3. The sustained release composition of claim 1, wherein the bisphoshphonate compound has the following structure:

4. The sustained release composition of claim 1, wherein the bisphosphonate compound has the following structure:

5. The sustained release composition of claim 1, wherein the bisphosphonate compound has the following structure:

6. The sustained release composition of claim 1, wherein the bisphosphonate compound has the following structure:

7. The sustained release composition of claim 1, wherein the bisphosphonate compound has the following structure:

8. The sustained release composition of claim 1, wherein the bisphosphonate is present from about 0.5% (w/w) to about 20% (w/w) of the total weight of the composition.