Liquid polymeric compositions for controlled release of bioactive substances

• US 6,733,767 B2
• Filed: 03/18/1999
• Issued: 05/11/2004
• Est. Priority Date: 03/19/1998
• Status: Expired due to Term

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Merck & Co., Inc.
• Inventors: Chern, Rey T., Zingerman, Joel R.
• Primary Examiner(s): Travers, Russell
• Assistant Examiner(s): SHARAREH, SHAHNAM J
• Application Number:
  US09/271,098
• Publication Number:
  US 20020064547A1
• Time in Patent Office: 1,881 Days
• Field of Search: 424/426, 424/424, 424/425, 424/422, 424/457, 424/458, 424/459, 424/489, 424/423, 604/891.1
• US Class Current: 424/426
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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

Abstract

Controlled release of hydrophobic bioactive substances in vivo over an extended time period and without “bursts” of drug release is achieved using a liquid polymeric composition including a polymer such as poly(lactide-co-glycolide) copolymer in a mixture of hydrophilic and lipophilic solvents.

Claims

1. A liquid polymeric composition for controlled release of eprinomectin consisting essentially of:

(a) 1 to 10% of eprinomectin;

(b) 1 to 10% of a poly(lactide-co-glycolide) copolymer;

wherein the weight ratio of the poly(lactide-co-glycolide) copolymer to the eprinomectin is 1;

1 or less and the ratio of lactide;

glycolide of the poly(lactide-co-glycolide) copolymer is from about 75;

25 to about 65;

35; and

(c) at least one lipophilic solvent or a mixture of hydrophilic and lipophilic solvents, wherein the volume ratio of the hydrophilic and lipophilic solvents is from about 80;

20 to about 5;

95.

2. The composition of claim 1 wherein the lipophilic solvent is triacetin.

3. The composition of claim 2 wherein the hydrophilic solvent is N-methyl pyrrolidone.

4. The composition of claim 3 consisting essentially of:

(a) 1 to 10% of eprinomectin;

(b) 1 to 10% of a poly(lactide-co-glycolide) copolymer;

wherein the weight ratio of the poly(lactide-co-glycolide) copolymer to the eprinomectin is 1;

1 or less and the ratio of lactide;

glycolide of the poly(lactide-co-glycolide) copolymer is from about 75;

25 to about 65;

35; and

(c) N-methyl pyrrolidone and triacetin, wherein the volume ratio of the N-methyl pyrrolidone and triacetin is from about 80;

20 to about 5;

95.

5. The composition of claim 4 wherein (a) consists essentially of about 5% eprinomectin.

6. The composition of claim 5 wherein the ratio of lactide:

glycolide of the poly(lactide-co-glycolide) copolymer is about 75;

25.

7. The composition of claim 6 wherein (b) is 5% poly(lactide-co-glycolide) copolymer.

8. The composition of claim 2 consisting essentially of:

(a) 1 to 10% of eprinomectin;

(b) 1 to 10% of a poly(lactide-co-glycolide) copolymer;

wherein the weight ratio of the poly(lactide-co-glycolide) copolymer to the eprinomectin is 1;

1 or less and the ratio of lactide;

glycolide of the poly(lactide-co-glycolide) copolymer is from about 75;

25 to about 65;

35; and

(c) triacetin.

9. The composition of claim 8 wherein (a) consists essentially of about 5% eprinomectin.

10. The composition of claim 9 wherein the ratio of lactide:

glycolide of the poly(lactide-co-glycolide) copolymer is about 75;

25.

11. The composition of claim 10 wherein (b) is 5% poly(lactide-co-glycolide) copolymer.

12. The composition of claim 1 wherein the hydrophilic solvent is N-methyl pyrrolidone.

13. A method for the controlled release of eprinomectin in a mammal which comprises injecting said mammal with the composition of any one of claims 1-12.

14. The method of claim 13 wherein the mammal is a bovine.

15. The method of claim 13 wherein the mammal is an ovine.

16. The method of claim 13 wherein the mammal is a canine.