Non-peptide polyamino acid bioerodible polymers

• US 4,638,045 A
• Filed: 02/19/1985
• Issued: 01/20/1987
• Est. Priority Date: 02/19/1985
• Status: Expired due to Term

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Langer, Robert S., Kohn, Joachim
• Primary Examiner(s): Foelak, Morton
• Assistant Examiner(s): Draper, Garnette D.
• Application Number:
  US06/703,153
• Time in Patent Office: 700 Days
• Field of Search: 260/112.5 R, 528/328, 530/323, 530/335, 530/337
• US Class Current: 530/323
• CPC Class Codes: C08G 69/10 Alpha-amino-carboxylic acids polysuccinimides C08G73/1092
• CPC Class Codes: Y10S 930/29 Polyamino acid or polypeptide with an uninterrupted series of peptide repeating units

Abstract

A novel bioerodible polymeric composition is provided comprising a plurality of monomer units of two or three amino acids which are polymerized via hydrolytically labile bonds at their respective side chains rather than at the amino or carboxylic acid terminals by amide bonds. Such polymers are useful for controlled release applications in vivo and in vitro for delivery of a wide variety of biologically and pharmacologically active ligands.

Claims

1. A bioerodible polymer formed by polymerizing a dipeptide formed exclusively of L-alpha amino acids of the formula:

##STR20## or by polymerizing a tripeptide formed exclusively of L-alpha amino acids of the formula;

##STR21## wherein at least one of Z or Y is an amine or carboxyl protecting group and wherein polymerization is effected through at least one of R₁, R₂ or R₃ without the formation of additional peptide bonds through the terminal, amine and carboxyl groups of said dipeptide or tripeptide.

2. The bioerodible polymer as recited in claim 1 wherein at least Y or Z is a pharmacologically active ligand.

3. The bioerodible polymer as recited in claim 2 wherein Y is a pharmacologically active ligand.

4. The bioerodible polymer as recited in claim 2 wherein Z is a pharmacologically active ligand.

5. The biodegradable polymer as recited in claim 1 wherein said hydrolytic labile bond is selected from the group consisting of imidocarbonate bonds, anhydride bonds, aromatic ester bonds, aliphatic ester bonds, sulfide bonds and imidazolide bonds.

6. The bioerodible polymer as recited in claim 1 wherein Z and Y comprise protecting groups of the amino terminal end and the carboxyl terminal end of the monomer unit.

7. The bioerodible polymer of claim 2 wherein the pharmacologically active ligand is a drug.

8. The bioerodible polymer of claim 7 wherein the drug is methotrexate.

9. The bioerodible polymer of claim 1 wherein at least one L-alpha amino acid is tyrosine.

10. The bioerodible polymer of claim 1 wherein at least one L-alpha amino acid is glutamine.

11. The bioerodible polymer of claim 1 wherein at least one L-alpha amino acid is phenylalanine.

12. The bioerodible polymer of claim 1 wherein at least one L-alpha amino acid is histidine.

13. The bioerodible polymer of claim 1 wherein at least one L-alpha amino acid is cysteine.

14. The composition of claim 1 which includes a pharmacologically active agent physically admixed within said polymer.