Speeding Cure Rate Of Bioadhesives

• US 20090131621A1
• Filed: 10/27/2008
• Published: 05/21/2009
• Est. Priority Date: 11/15/2007
• Status: Active Grant

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: Tyco Healthcare Group LP (Medtronic Plc)
• Inventors: Abuzaina, Ferass
• Granted Patent: US 8,500,947 B2
• Time in Patent Office: Days
• US Class Current: 528/59
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: C08G 18/10 Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
• CPC Class Codes: C08G 18/12 using two or more compounds having active hydrogen in the first polymerisation step
• CPC Class Codes: C08G 18/3228 acyclic
• CPC Class Codes: C08G 18/4252 derived from polyols containing polyether groups and polycarboxylic acids
• CPC Class Codes: C08L 75/04 Polyurethanes
• CPC Class Codes: C09D 175/06 from polyesters

Abstract

The present disclosure provides compositions having reduced viscosity which may be used as adhesives or tissue sealants, and includes methods for speeding the cure rate of such compositions.

Claims

1. A method comprising:

contacting at least one isocyanate-terminated component with a dilute solution comprising at least one amine at a concentration of from about 0.01 weight percent to about 0.5 weight percent of the solution; and

allowing the at least one isocyanate-terminated component and the at least one amine to react in situ thereby forming a biocompatible composition.

2. The method of claim 1, wherein the at least one isocyanate-terminated component is of the formula:

wherein X is a polyether, a polyester or a polyether-ester group; and

R is an aliphatic or aromatic group and the at least one isocyanate-terminated component has a molecular weight of from about 1000 g/mol to about 20000 g/mol.

3. The method of claim 2, wherein X is a polyether selected from the group consisting of polyethylene glycol, polypropylene glycol, polybutylene glycol, polytetramethylene glycol, polyhexamethylene glycol, and combinations thereof.

4. The method of claim 2, wherein X is a polyester selected from the group consisting of trimethylene carbonate, ε

-caprolactone, p-dioxanone, glycolide, lactide, 1,5-dioxepan-2-one, polybutylene adipate, polyethylene adipate, polyethylene terephthalate, and combinations thereof.

5. The method of claim 2, wherein X is a polyether-ester group selected from the group consisting of polyethylene glycol-polycaprolactone, polyethylene glycol-polylactide, polyethylene glycol-polyglycolide, and combinations thereof.

6. The method of claim 1, wherein the amine is selected from the group consisting of bis(3-aminopropyl)amine, spermine, polyetheramine, trilysine, ethylenediamine, N-ethylethylenediamine, N,N′

-diethylethylenediamine, butane-1,4-diamine, pentane-1,5-diamine, hexane-1,6-diamine, phenylene diamine, and combinations thereof having a molecular weight of from about 50 g/mol to about 500 g/mol.

7. The method of claim 1, wherein the solution comprises at least one solvent selected from the group consisting of water, ethanol, triethylene glycol, diglyme, triglyme, tetraglyme, polyethylene glycols, methoxy-polyethylene glycols, dimethylformamide, dimethylsulfoxide, dimethylacetamide, gamma-butyrolactone, N-methylpyrollidone, methyl ethyl ketone, cyclohexanone, diethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoisobutyl ether, diisobutyl ketone, diacetone alcohol, ethyl amyl ketone, ethyl lactate, tetrahydrofuran, ethyl acetate, isopropyl acetate, butyl acetate, isopropanol, butanol, acetone, and combinations thereof.

8. The method of claim 1, wherein the ratio of the amine to the at least one isocyanate-terminated component is from about 1:

10 to about 10;

1 w/w.

9. The method of claim 1, wherein the composition exhibits a lap shear of from about 0.8 kg to about 2 kg.

10. The method of claim 1, wherein the at least one isocyanate-terminated component and the at least one amine form the biocompatible composition within from about 1 second to about 5 minutes after contact.

11. An adhesive comprising the biocompatible composition of claim 1.

12. A method comprising:

contacting at least one isocyanate-terminated component with a dilute solution comprising at least one amine selected from the group consisting of bis(3-aminopropyl)amine, spermine, polyetheramine, trilysine, ethylenediamine, N-ethylethylenediamine, N,N′

-diethylethylenediamine, butane-1,4-diamine, pentane-1,5-diamine, hexane-1,6-diamine, phenylene diamine, and combinations thereof having a molecular weight of from about 50 g/mol to about 500 g/mol, at a concentration of from about 0.01 percent by weight to about 0.5 percent by weight of the solution; and

allowing the at least one isocyanate-terminated polyurethane and the at least one amine to react in situ thereby forming a biocompatible composition.

13. The method of claim 12, wherein the at least one isocyanate-terminated component is of the formula:

wherein X is a polyether, a polyester or a polyether-ester group; and

R is an aliphatic or aromatic group and the at least one isocyanate-terminated component has a molecular weight of from about 1500 g/mol to about 10000 g/mol.

14. The method of claim 13, wherein X is a polyether selected from the group consisting of polyethylene glycol, polypropylene glycol, polybutylene glycol, polytetramethylene glycol, polyhexamethylene glycol, and combinations thereof.

15. The method of claim 13, wherein X is a polyester selected from the group consisting of trimethylene carbonate, ε

-caprolactone, p-dioxanone, glycolide, lactide, 1,5-dioxepan-2-one, polybutylene adipate, polyethylene adipate, polyethylene terephthalate, and combinations thereof.

16. The method of claim 13, wherein X is a polyether-ester group selected from the group consisting of polyethylene glycol-polycaprolactone, polyethylene glycol-polylactide, polyethylene glycol-polyglycolide, and combinations thereof.

17. The method of claim 12, wherein the solution comprises at least one solvent selected from the group consisting of water, ethanol, triethylene glycol, diglyme, triglyme, tetraglyme, polyethylene glycols, methoxy-polyethylene glycols, dimethylformamide, dimethylacetamide, gamma-butyrolactone, N-methylpyrollidone, methyl ethyl ketone, cyclohexanone, diethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoisobutyl ether, diisobutyl ketone, diacetone alcohol, ethyl amyl ketone, ethyl lactate, tetrahydrofuran, ethyl acetate, isopropyl acetate, butyl acetate, isopropanol, butanol, acetone, and combinations thereof.

18. The method of claim 12, wherein the ratio of the amine to the at least one isocyanate-terminated component is from about 1:

10 to about 10;

1 w/w.

19. The method of claim 12, wherein the composition exhibits a lap shear of from about 0.8 kg to about 2 kg.

20. The method of claim 12, wherein the at least one isocyanate-terminated component and the at least one amine form the biocompatible composition within from about 1 second to about 5 minutes after contact.