Biodegradable injectable drug delivery polymer

• US 5,384,333 A
• Filed: 03/17/1992
• Issued: 01/24/1995
• Est. Priority Date: 03/17/1992
• Status: Expired due to Fees

• Current Assignee: University of Miami
• Original Assignee: University of Miami
• Inventors: Davis, Patricia A., Cousins, Scott
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): AZPURU, CARLOS A
• Application Number:
  US07/852,948
• Time in Patent Office: 1,043 Days
• Field of Search: 424/405, 424/408, 424/417, 424/418, 424/420, 424/427, 424/428, 424/450, 424/78.04, 424/78.38, 424/489, 424/501, 523/500, 264/4.1, 264/4.33, 264/4.4, 428/402.21, 514/772.3
• US Class Current: 514/772.3
• 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
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)

Abstract

A bio-injectable drug composition which provides long term drug release. The drug composition is made up of a pharmaceutically active agent in a biodegradable polymer matrix, where the polymer matrix is a solid at temperatures in the range 20° to 37° C. and is flowable at temperatures in the range 38° to 52° C.

Claims

1. A drug delivery composition for injection into a body, comprising a pharmaceutically active agent and biodegradable polymer which are physically mixed together, wherein the polymer comprises from 30 to 99.5% by weight of said drug delivery composition, is solid at a temperature in the range 20°

to 37°

C. and flowable in the range of 38°

to 52°

C., and is a block co-polymer of formula;

space="preserve" listing-type="equation">A--B--A

wherein A is a hydrophobic polymer or oligomer and B is a hydrophilic polymer or oligomer.

3. A drug delivery composition according to claim 1, wherein A is selected from the group consisting of polyglycolic acid, polyethylene terephthalate, polybutyl lactone polycaprolactone, D-polylactic acid, L-polylactic acid, polyglutamic acid, poly L-lysine, and poly L-aspartic acid;

and wherein B is selected from the group consisting of polyethylene glycol, polypropylene glycol and polyvinyl alcohol.

4. A drug delivery composition according to claim 1, wherein the biodegradable polymer is a polymer of formula:

space="preserve" listing-type="equation">H[O(CH.sub.2).sub.5 C].sub.n --[OCH.sub.2 CH.sub.2 ].sub.m --[OC(CH.sub.2).sub.5 O].sub.n --H

wherein m is in the range 9.09 to 45.45 and n is in the range 6.16 to 45.45.

5. A drug delivery composition as claimed in claim 1, wherein the pharmaceutically active agent is selected from gancyclovir, 5-fluorouracil, acyclovir, dexamethasone, triamcinolone, prednisone, floxuridine, doxorubicin, daunorubicin, mitomycin, cytarabine, methotrexate and thioguanine.

6. A drug delivery composition according to claim 5 wherein the pharmaceutically active agent is selected from gancyclovir and 5-fluorouracil.

7. A drug composition according to claim 1, wherein the pharmaceutically active agent is present in the amount 0.5 to 70% by weight relative to the total weight of the composition.

8. A drug delivery composition according to claim 7, wherein the pharmaceutically active agent is present in an amount 1 to 35% by weight relative to the total weight of the composition.

9. A drug delivery composition according to claim 8, wherein the pharmaceutically active agent is present in an amount 2% to 25% by weight relative to the total weight of the composition.

10. A drug delivery composition according to claim 1 comprising a pharmaceutically active agent and biodegradable tri-block copolymer of the formula

2. A drug delivery composition for injection into a body, comprising a pharmaceutically active agent physically mixed with a biodegradable block co-polymer of formula:

space="preserve" listing-type="equation">A--B--A

wherein A is a hydrophobic polymer or oligomer and B is a hydrophilic polymer or oligomer;

wherein the biodegradable block co-polymer comprises from 30 to 99.5% by weight of said drug delivery composition and is solid at a temperature in the range 20°

to 37°

C. and flowable in the range of 38°

to 52°

C.; and

wherein A is selected from the group consisting of polyglycolic acid, polyethylene terephthalate, polybutyl lactone polycaprolactone, D-polylactic acid, L-polylactic acid, polyglutamic acid, poly L-lysine, and poly L-aspartic acid; and

wherein B is selected from the group consisting of polyethylene glycol, polypropylene glycol and polyvinyl alcohol.