Method comprising contacting tissue with a cross-linkable polyester prepolymer

• US 8,691,203 B2
• Filed: 03/23/2012
• Issued: 04/08/2014
• Est. Priority Date: 01/12/2006
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Bettinger, Christopher J., Ferreira, Lino Da Silva, Karp, Jeffrey M., Langer, Robert S., Nijst, Christiaan, Zumbuehl, Andreas, Burdick, Jason, Kim, Sonia J., Bruggeman, Joost P.
• Primary Examiner(s): Naff, David M
• Application Number:
  US13/428,869
• Publication Number:
  US 20120269761A1
• Time in Patent Office: 746 Days
• Field of Search: None
• US Class Current: 424/78.06
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/48 Reproductive organs
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: C08G 63/6854 derived from polycarboxylic acids and polyhydroxy compounds
• CPC Class Codes: C08J 2367/00 Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain of polyester-amides C08J2377/12; of polyester-imides C08J2379/08; Derivatives of such polymers
• CPC Class Codes: C08J 2367/07 having terminal carbon-to-carbon unsaturated bonds
• CPC Class Codes: C08J 3/24 Crosslinking, e.g. vulcanising, of macromolecules mechanical aspects B29C35/00; crosslinking agents C08K
• CPC Class Codes: C08J 3/246 Intercrosslinking of at least two polymers
• CPC Class Codes: C08K 5/0025 Crosslinking or vulcanising agents; including accelerators
• CPC Class Codes: C08L 67/00 Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain of polyester-amides C08L77/12; of polyester-imides C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 67/07 having terminal carbon-to-carbon unsaturated bonds
• CPC Class Codes: C12N 11/082 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: C12N 11/087 Acrylic polymers
• CPC Class Codes: C12N 11/096 : Polyesters; Polyamides

Abstract

The present inventions in various aspects provide elastic biodegradable polymers. In various embodiments, the polymers are formed by the reaction of a multifunctional alcohol or ether and a difunctional or higher order acid to form a pre-polymer, which is cross-linked to form the elastic biodegradable polymer. In preferred embodiments, the cross-linking is performed by functionalization of one or more OR groups on the pre-polymer backbone with vinyl, followed by photopolymerization to form the elastic biodegradable polymer composition or material. Preferably, acrylate is used to add one or more vinyls to the backbone of the pre-polymer to form an acrylated pre-polymer. In various embodiments, acrylated pre-polymers are co-polymerized with one or more acrylated co-polymers.

Claims

1. A method comprising contacting tissue with a cross-linkable polyester prepolymer,

wherein the cross-linkable polyester prepolymer comprises a polymeric unit of the general formula

(-A-B-)_n,

wherein A represents a substituted or unsubstituted ester, wherein A comprises a free hydroxyl group prior to cross-linking,

B represents a substituted or unsubstituted ester comprising at least two acid ester functionalities,

n represents an integer greater than 1, and

cross-linking the cross-linkable polyester pre-polymer between a plurality of the A components of the polyester to form an adhesive, wherein the cross-links contain a single dioic acid ester functionality.

2. The method of claim 1, wherein the cross-linked polyester has the general formula (I)

3. The method of claim 2, wherein p=8.

4. The method of claim 1, wherein the average ratio of the number of cross-links to the number of (-A-B-)_n polymeric units is less than about 0.4.

5. The method of claim 1, wherein the average ratio of the number of cross-links to the number of (-A-B-)_n polymeric units is greater than about 0.5.

6. The method of claim 1, wherein the cross-linked polyester is cross-linked to a substituted or unsubstituted alkane through at least a portion of the A components of the polyester.

7. The method of claim 1, wherein a plurality of unit A of the cross-linkable polyester pre-polymer comprise an acrylate group and the acrylate groups are cross-linked to form the adhesive.

8. The method of claim 7, wherein the cross-linked polyester has the general formula (II)

9. The method of claim 8, wherein p=8.

10. The method of claim 1, wherein the cross-link density is less than 1%.

11. The method of claim 10, wherein the cross-link density is less than 0.5%.

12. The method of claim 11, wherein the cross-link density is less than 0.05%.

13. The method of claim 1, wherein the adhesive is one or more of non-toxic to humans, biocompatible, and bioabsorbable.

14. The method of claim 1, wherein the adhesive promotes hemostasis.

15. The method of claim 1, wherein the adhesive promotes wound closure.

16. The method of claim 1, wherein the adhesive adheres a medical device to tissue.

17. The method of claim 1, wherein the cross-linkable polyester pre-polymer is at least partially cross-linked in vivo.