Bioadhesive polymers with catechol functionality

• US 20050201974A1
• Filed: 12/09/2004
• Published: 09/15/2005
• Est. Priority Date: 12/09/2003
• Status: Abandoned Application

• Current Assignee: Spherics, Inc.
• Original Assignee: Spherics, Inc.
• Inventors: Donnelly, Ryan, Schestopol, Marcus, Jacob, Jules, Nangia, Avinash, Mathiowitz, Edith, Shaked, Ze'ev, Ricketts, Thomas
• Application Number:
  US11/009,327
• Publication Number:
  US 20050201974A1
• Time in Patent Office: Days
• US Class Current: 424/78.270
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C08F 222/06 Maleic anhydride
• CPC Class Codes: C08F 8/32 by reaction with amines
• CPC Class Codes: C08G 63/91 Polymers modified by chemical after-treatment
• CPC Class Codes: C08G 63/912 derived from hydroxycarboxylic acids
• CPC Class Codes: C09J 167/00 Adhesives based on polyesters obtained by reactions forming a carboxylic ester link in the main chain based on polyester-amides C09J177/12; based on polyester-imides C09J179/08; Adhesives based on derivatives of such polymers
• CPC Class Codes: C09J 167/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C09J167/06 takes precedence

Abstract

Polymers with improved bioadhesive properties and methods for improving bioadhesion of polymers have been developed. A compound containing an aromatic group which contains one or more hydroxyl groups is grafted onto a polymer or coupled to individual monomers. In one embodiment, the polymer is a biodegradable polymer. In another embodiment, the monomers may be polymerized to form any type of polymer, including biodegradable and non-biodegradable polymers. In some embodiments, the polymer is a hydrophobic polymer. In the preferred embodiment, the aromatic compound is catechol or a derivative thereof and the polymer contains reactive functional groups. In the most preferred embodiment, the polymer is a polyanhydride and the aromatic compound is the catechol derivative, DOPA. These materials display bioadhesive properties superior to conventional bioadhesives used in therapeutic and diagnostic applications. These bioadhesive materials can be used to fabricate new drug delivery or diagnostic systems with increased residence time at tissue surfaces, and consequently increase the bioavailability of a drug or a diagnostic agent. In a preferred embodiment, the bioadhesive material is a coating on a controlled release oral dosage formulation and/or forms a matrix in an oral dosage formulation.

Claims

1. A bioadhesive material comprising a polymeric backbone and a side chain or side group containing an aromatic group substituted with one or more hydroxyl groups.

2. The material of claim 1, wherein the aromatic group is catechol.

3. The material of claim 2, wherein the aromatic group is a derivative of catechol.

4. The material of claim 3, wherein the derivative of catechol is 3,4-dihydroxyphenylalanine (DOPA).

5. The material of claim 1, wherein the polymeric backbone is a hydrophobic polymer.

6. The material of claim 5, wherein the hydrophobic polymer is selected from the group consisting of polyanhydrides, polyacrylates, polyorthoesters, polyesters, and polyhydroxy acids.

7. The material of claim 6, wherein the hydrophobic backbone is a polyanhydride.

8. The material of claim 1, wherein at least 10% of the monomers in the polymeric backbone contain a side chain containing an aromatic group.

9. The material of claim 8, wherein at least 50% of the monomers in the polymeric backbone contain a sidechain containing an aromatic group.

10. The material of claim 1, further comprising a therapeutic, prophylactic, or diagnostic agent.

11. The material of claim 9, wherein the therapeutic agent is L-3,4-dihydroxyphenylalanine (levodopa).

17. The method of claim 11, wherein the compound comprising an aromatic group is a catechol derivative.

18. The method of claim 17, wherein the catechol derivative is 3,4-dihydroxyphenylalanine (DOPA).

12. A method for forming a bioadhesive material, comprising reacting a polymer with a compound containing an aromatic group substituted with one or more hydroxyl groups or a poly(amino acid), peptide or protein containing an aromatic group substituted with one or more hydroxyl groups, wherein the a poly(amino acid), peptide or protein has a molecular weight of 20 kDa or less.

13. The method of claim 12, wherein the polymer comprises an amino reactive group and wherein the compound comprises an amino group.

14. The method of claim 12, wherein the polymer is a hydrophobic polymer.

15. The method of claim 14, wherein the hydrophobic polymer is selected from the group consisting of polyanhydrides, polyacrylates, polyorthoesters, polyesters, and polyhydroxy acids.

16. The method of claim 14, wherein the hydrophobic polymer is a polyanhydride.

19. A method for forming a bioadhesive material, comprising reacting a monomer with a compound containing an aromatic group substituted with one or more hydroxyl groups or a poly(amino acid), peptide or protein containing an aromatic group substituted with one or more hydroxyl groups, wherein the a poly(amino acid), peptide or protein has a molecular weight of 20 kDa or less, and polymerizing the monomer.

20. The method of claim 19, wherein the monomer comprises an amino reactive group and wherein the compound comprises an amino group.