Biodegradable polymers of lactones

• US 4,379,138 A
• Filed: 12/28/1981
• Issued: 04/05/1983
• Est. Priority Date: 12/28/1981
• Status: Expired due to Fees

• Current Assignee: Research Triangle Institute
• Original Assignee: Research Triangle Institute
• Inventors: Pitt, Colin G., Schindler, Anton E.
• Primary Examiner(s): Nielsen, Earl A.
• Application Number:
  US06/335,188
• Time in Patent Office: 463 Days
• Field of Search: 528/354, 528/359, 424/78, 128/1 R
• US Class Current: 514/772.7
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 15/26 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof A61L15/225 takes precedence
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/60 Materials for use in artificial skin
• CPC Class Codes: C08G 63/08 Lactones or lactides
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Homopolymers and copolymers of lactones are prepared by ring-opening polymerization of a mixture of lactones which includes a monolactone, such as ε-caprolactone, and a dilactone, such as bis-2,2-(ε-caprolacton-4-yl)propane, which is capable of forming crosslinks. The resulting polymers range from tough and partially crystalline to amorphous, elastomeric materials, depending on the monomer composition and proportions. Additionally, these polymers may be designed to achieve different degrees of permeability and rates of biodegradation. As such, they are useful for the controlled delivery of medicinal agents and as surgical aids and temporary artificial biomaterials such as skin substitutes and burn dressings.

Claims

1. An elastomeric, biodegradable polymer formed by the opening polymerization of at least one monocyclic lactone and at least one polycyclic dilactone containing two lactone groups, each of which may be polymerized by ring opening to form a two-dimensional polymer.

2. The polymer of claim 1 wherein said monocyclic lactone is selected from the group consisting of glycolide, DL-lactide, L-lactide, δ

-valerolactone, ε

-caprolactone, ω

-dodecalactone and the C_1-8 alkyl and aryl derivatives thereof.

3. The polymer of claim 1 or 2 wherein said dilactone is of the formula:

##STR2## wherein R₁ and R₂, each of which may be the same or different, is an alkyl group of 1 to 8 carbon atoms.

4. The polymer of claim 3 wherein said dilactone is 2,2-bis(ε

-caprolacton-4-yl)propane.

5. The polymer of claim 4 wherein the monocyclic lactone is a mixture of δ

-valerolactone and ε

-caprolactone.

6. The polymer of claim 1 containing from about 0.5 to about 20 mole percent of said dilactone.

7. The polymer of claim 6 wherein said dilactone is present in an amount ranging from about 3 to about 10 mole percent.

8. A process for the preparation of the elastomeric biodegradable polymer of claim 1 which comprises the steps of:

(a) mixing at least one monocyclic lactone, and at least one polycyclic dilactone containing two lactone groups, together with a polymerization catalyst;

(b) degassing the mixture obtained in step (a); and

(c) heating the degassed mixture for a period of time sufficient to polymerize same.

9. A process according to claim 8 wherein said degassed mixture is heated at a temperature ranging from about 80°

to about 180°

C.

10. A process according to claim 9 wherein the degassed mixture is heated from about 125°

to 150°

C.

11. A process according to claim 9 wherein said degassed mixture is heated for a period of from 10 to about 50 hours.

12. A pharmaceutical preparation comprising a pharmaceutically acceptable medicinal agent as an active ingredient dissolved or dispersed in the biodegradable polymer of claim 1.

13. A prosthesis formed from the polymer of claim 1.