SUSTAINED RELEASE COMPOSITION AND MANUFACTURING METHOD THEREOF

• US 20090169632A1
• Filed: 12/31/2007
• Published: 07/02/2009
• Est. Priority Date: 12/31/2007
• Status: Active Grant

• Current Assignee: Industrial Technology Research Institute
• Original Assignee: Industrial Technology Research Institute
• Inventors: Lu, Jui-Mei, Lo, Yo Wen, Liu, Chia-Wen, Chen, Sung En, Lai, Po Hong, Lin, John Jiang Hann, Sheu, Ming-Thau, Lin, Min-Ying, Li, Chiao Pin
• Granted Patent: US 9,161,943 B2
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A sustained release composition comprising a polymer and manufacturing method thereof. The sustained release composition comprises a polymer, a bioactive agent, and a release rate determined agent, wherein the release rate determined agent is dispersed in the sustained release composition to control the release rate of the bioactive agent. The method comprises providing an oil phase comprising a bioactive agent, a polymer, and a release rate determined agent; providing an aqueous phase comprising a surfactant; mixing the oil phase with the aqueous phase to form the sustained release composition having a controlled release effect.

Claims

1. A sustained release composition without lag phase comprising of a polymer, a bioactive agent, and a release rate determined agent, wherein the bioactive agent and the release rate determined agent are dispersed in the sustained release composition, and the release rate determined agent control the release rate of the bioactive agent.

2. The sustained release composition as claimed in claim 1, wherein the bioactive agent comprises proteins, nucleic acids, carbohydrates, peptides, immunogens, or hormones.

3. The sustained release composition as claimed in claim 1, wherein the bioactive agent comprises small molecule pharmaceutical substances, antineoplastic agents, antihistamines, antipsychotics, anti-ulcer agents, anti-cancer agents, cardiovascular agents, bronchodilators, vasodilators, central nervous system agents or narcotic antagonists.

4. The sustained release composition as claimed in claim 1, wherein the polymer is a biodegradable polymer.

5. The sustained release composition as claimed in claim 1, wherein the polymer comprises phospholipids, lecithin, polyglycolate, poly(lactide)s, poly(glycolide)s, polylactide-co-glycolide (PLGA), polyglutamic acid, polycaprolactone (PCL), polyamino acid, polydioxanone, polyhydroxybutyrate, polyphophazenes, polyesterurethane, polycarbosyphenoxypropane-cosebacic acid, polyorthosester, polycarbonates, polyesteramides, polyanhydrides, polyacetyls, polycyanoacrylates, polyetheresters, poly(alkylene alkylate)s, or copolymers thereof.

6. The sustained release composition as claimed in claim 1, wherein the release rate determined agent, is present in amounts of about 1 to 50% by weight of the total weight of the sustained release composition.

7. The sustained release composition as claimed in claim 1, wherein the release rate determined agent comprises Span®

80, Span®

85, oleic acid, PEG-PCL di-block copolymer, glyceryl tricaprylate, Pluronic®

(F68), Tween®

80 or vitamin E-TPGS.

8. The sustained release composition as claimed in claim 1, wherein the sustained release composition continually releases the bioactive agent.

9. The sustained release composition as claimed in claim 1, wherein the sustained release composition has an encapsulation rate of bioactive agent exceeding 70%.

10. The sustained release composition as claimed in claim 1, wherein the sustained release composition is a microsphere, microparticle, or microcapsule.

11. The sustained release composition as claimed in claim 8, wherein the sustained release composition has a diameter exceeding 5 μ

m.

12. The sustained release composition as claimed in claim 1, wherein the sustained release composition is used for intramuscular or subcutaneous injection.

14. The method as claimed in claim 12, wherein the oil phase further comprises a solvent.

16. The method as claimed in claim 12, wherein the bioactive agent comprises proteins, nucleic acids, carbohydrates, peptides, immunogens, or hormones.

17. The method as claimed in claim 12, wherein the bioactive agent comprises small molecule pharmaceutical substances, antineoplastic agents, antihistamines, antipsychotics, anti-ulcer agents, anti-cancer agents, cardiovascular agents, bronchodilators, vasodilators, central nervous system agents or narcotic antagonists.

18. The method as claimed in claim 12, wherein the polymer is a biodegradable polymer.

19. The method as claimed in claim 12, wherein the polymer comprises phospholipids, lecithin, poly(lactide)s, poly(glycolide)s, polylactide-co-glycolide (PLGA), polyglutamic acid, polycaprolactone (PCL), polyamino acid, polydioxanone, polyhydroxybutyrate, polyphophazenes, polyesterurethane, polycarbosyphenoxypropane-cosebacic acid, polycarbonates, polyesteramides, polyanhydrides, polyacetyls, polycyanoacrylates, polyetheresters, poly(alkylene alkylate)s, or copolymers thereof.

20. The method as claimed in claim 12, wherein the surfactant comprises polyvinyl alcohol (PVA), NP-5, Triton x-100, Tween 80, PEG 200-800, sodium dodecyl sulfate (SDS), alcohol ethoxylates, alkylphenol ethoxylates, secondary alcohol ethoxylates, fatty acid ester, or alkyl polyglycosides.

21. The method as claimed in claim 12, wherein the release rate determined agents has a final concentration of about 1 to 50% by weight.

22. The method as claimed in claim 12, wherein the sustained release composition is a microsphere, microparticle, or microcapsule.

23. A method of treating an animal, comprising administering a pharmaceutically effective amount of the sustained release composition of claim 1.

24. The method as claimed in claim 20, wherein the animal is a mammalian.

25. The method as claimed in claim 20, wherein the animal is a human.

13. A method for manufacturing a sustained release composition, comprising:

(a) providing an oil phase comprising a bioactive agent, a polymer, and vitamin E-TPGS;

(b) providing an aqueous phase comprising a surfactant;

(c) mixing the oil phase with the aqueous phase to form the sustained release composition; and

(d) recovering the composition.

15. The method as claimed in claim 13, wherein the solvent comprises methylene chloride, ethyl acetate, benzyl alcohol, acetone, acetic acid, propylene carbonate, dichloromethane, chloroform, 1,4-dioxane, dimethylformamide (DMF), dimethyl sulphoxide (DMSO), toluene, or tetrahydrofuran (THF).