ADHESIVE FORMULATIIONS

• US 20080293910A1
• Filed: 05/21/2008
• Published: 11/27/2008
• Est. Priority Date: 05/24/2007
• Status: Abandoned Application

• Current Assignee: Tyco Healthcare Group LP (Medtronic Plc)
• Original Assignee: Tyco Healthcare Group LP (Medtronic Plc)
• Inventors: Hadba, Ahmad R., Kapiamba, Mbiya
• Application Number:
  US12/124,414
• Publication Number:
  US 20080293910A1
• Time in Patent Office: Days
• US Class Current: 528/70
• CPC Class Codes: A61L 24/04 containing macromolecular materials

Abstract

The disclosure relates to biocompatible components useful for forming compositions for use as medical/surgical synthetic adhesives and sealants. Biocompatible components of the present disclosure may include a multifunctional amine or multifunctional polyol core, with isocyanate and/or polyalkylene oxide arms, which may optionally be capped with electrophilic or nucleophilic groups. These biocompatible components may, in embodiments, be combined with optional cross linkers to form adhesive and/or sealant compositions.

Claims

1. A biocompatible component selected from the group consisting of:

wherein I comprises a core selected from the group consisting of multifunctional polyols and multifunctional amines,

X is selected from the group consisting of carboxylic acids, isocyanates, isothiocyanates, and combinations thereof,

Y is selected from the group consisting of polyalkylene oxides, polyether polyesters, polyether polyurethanes, polyether polyester urethanes, and combinations thereof,

Z is selected from the group consisting of N-hydroxysuccinimide, N-hydroxysulfosuccinimide, pentafluorophenol, p-nitrophenol, and combinations thereof,

R is selected from the group consisting of alkyl, aryl, ether, and combinations thereof, and

w is a number from about 3 to about 250.

2. The biocompatible component of claim 1, wherein the multifunctional polyol is selected from the group consisting of polyether polyols, polyester polyols, branched chain ethoxylated alcohols, alkoxylated alcohols, polyvinyl alcohols, polyhydric alcohols, carboxylic acid esters of polyhydric alcohols, polyglycols, polylactone polyols, and combinations thereof.

3. The biocompatible component of claim 1, wherein the multifunctional polyol is selected from the group consisting of hexane-1,2,6-triol, polycaprolactone triol, glycerol, pentaerythritol, sorbitol, mannitol, trimethylol propane, diethylene glycol, pentaerythritol ethoxylate, pentaerythritol propoxylate, dipentaerythritol, and combinations thereof.

4. The biocompatible component of claim 1, wherein the multifunctional amine is selected from the group consisting of poly(allyl amine), poly(L-lysine), polyalkylene oxides having three or more amine groups, polyethylene oxide/polypropylene oxide copolymers possessing three or more amine groups, trilysine, diethylene triamine, di(heptamethylene)triamine, di(trimethylene)triamine, bis(hexamethylene)triamine, triethylene tetramine, tripropylene tetramine, tetraethylene pentamine, hexamethylene heptamine, pentaethylene hexamine, dimethyl octylamine, dimethyl decylamine, rh-collagen, rh-gelatin, chitosan, and combinations thereof.

5. The biocompatible component of claim 1, wherein the polyalkylene oxide is selected from the group consisting of polyethylene glycols, polypropylene glycols, polyethylene oxides, polypropylene oxides, polyethylene glycols with lactide linkages, polypropylene glycol-co-polyethylene oxide copolymers, polyethylene oxide/polypropylene oxide copolymers, and combinations thereof.

6. The biocompatible component of claim 1, wherein the isocyanate comprises a diisocyanate selected from the group consisting of aromatic diisocyanates, aliphatic diisocyanates and alicyclic diisocyanates.

7. The biocompatible component of claim 6, wherein the diisocyanate is selected from the group consisting of 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, 2,2′

-diphenylmethane diisocyanate, 2,4′

-diphenylmethane diisocyanate, 4,4′

-diphenylmethane diisocyanate, diphenyldimethylmethane diisocyanate, dibenzyl diisocyanate, naphthylene diisocyanate, phenylene diisocyanate, xylylene diisocyanate, 4,4′

-oxybis(phenyl isocyanate), 2,4,6-trimethyl-1,3-phenylene diisocyanate, tetramethylxylylene diisocyanate, tetramethylene diisocyanate, hexamethylene diisocyanate, lysine diisocyanate, 2-methylpentane-1,5-diisocyanate, 3-methylpentane-1,5-diisocyanate, hexane-1,6-diisocyanate, 2,2,4-trimethylhexamethylene diisocyanate, isophorone diisocyanate, cyclohexane diisocyanate, hydrogenated xylylene diisocyanate, hydrogenated diphenylmethane diisocyanate, hydrogenated trimethylxylylene diisocyanate, and combinations thereof.

8. A composition comprising the biocompatible component of claim 1 in combination with a cross linker.

9. The composition of claim 8, wherein the cross linker comprises a polyfunctional amine cross linker selected from the group consisting of primary amines, secondary amines, diamines, aromatic amines, polyamines, polyamidoamines, and combinations thereof.

10. The composition of claim 8, wherein the cross linker comprises an amine cross linker selected from the group consisting of poly(allyl amine), poly(L-lysine), polyalkylene oxides having two or more amine functional groups, spermidine, spermine, 1,4-bis(3-aminopropyl)piperazine, diaminobicyclooctane, triethylamine, diisopropylethylamine, ethylene diamine, 1,4-butane diamine, hexamethylene diamine, diethylene triamine, triethylene tetramine, lysine, lysine containing polypeptides, arginine, arginine containing polypeptides, tetraethylene pentamine, bishexamethylene triamine, N,N′

-Bis(3-aminopropyl)-1,2-ethane diamine, N-(3-Aminopropyl)-1,3-propane diamine, N-(2-aminoethyl)-1,3 propane diamine, cyclohexane diamine, 4,4′

-methylene biscyclohexane amine, 4′

4′

-methylene bis(2-methylcyclohexane amine), isophorone diamine, phenalkylene polyamines, di-(4-aminophenyl)sulfone, di-(4-aminophenyl)ether, 2,2-bis(4-aminophenyl)propane, 4,4′

-diamino diphenylmethane, 3,3′

-dimethyl-4,4′

-diaminodiphenyl methane, m-phenylene diamine, p-phenylene diamine, m-xylylene diamine, toluene diamine, 4,4′

-methylene dianiline, benzidine, 4,4′

-thiodianiline, 4-methoxy-1,3-phenyldiamine, 2,6-diaminopyridine, dianisidine, 4,9-dioxadodecane-1,12-diamine, 4,7,10-trioxamidecane-1,12-diamine, bis(3-amino propyl)polytetrahydrofurans, Bis(3-aminopropyl)amine, 1,2-Bis(3-aminopropylamino)ethane, polyoxyalkylene amines, and combinations thereof.

11. The composition of claim 8, wherein the biocompatible component of claim 1 is present in an amount from about 50 to about 90 percent by weight of the composition, and the cross linker is present in an amount from about 10 to about 50 percent by weight of the composition.

12. A method for closing a wound comprising:

applying the composition of claim 8 to said wound; and

allowing the composition to set thereby closing said wound.

13. A method for sealing a leak in animal tissue comprising:

applying the composition of claim 8 to said leak; and

allowing the composition to set thereby sealing said leak.

14. A method for adhering a medical device to a surface of animal tissue comprising:

applying the composition of claim 8 to said device, said surface or both;

bringing the device, composition and surface into contact with each other; and

allowing the composition to set thereby adhering the device and surface to each other.

15. A method comprising:

providing a multifunctional amine possessing a functionality of at least 3;

contacting the multifunctional amine with a diisocyanate to form an isocyanate functionalized polyamine;

contacting the isocyanate functionalized polyamine with a polyalkylene oxide to form a polyalkylene oxide capped polyamine;

contacting the polyalkylene oxide capped polyamine with an anhydride to form a carboxylic acid group at the terminus of the polyalkylene oxide; and

reacting the carboxylic acid group at the terminus of the polyalkylene oxide with N-hydroxysuccinimide.

16. The method of claim 15, wherein the multifunctional amine is selected from the group consisting of poly(allyl amine), poly(L-lysine), polyalkylene oxides having three or more amine groups, polyethylene oxide/polypropylene oxide copolymers possessing three or more amine groups, trilysine, diethylene triamine, di(heptamethylene)triamine, di(trimethylene)triamine, bis(hexamethylene)triamine, triethylene tetramine, tripropylene tetramine, tetraethylene pentamine, hexamethylene heptamine, pentaethylene hexamine, dimethyl octylamine, dimethyl decylamine, rh-collagen, rh-gelatin, chitosan, and combinations thereof.

17. The method of claim 15, wherein the diisocyanate is selected from the group consisting of 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, 2,2′

-diphenylmethane diisocyanate, 2,4′

-diphenylmethane diisocyanate, 4,4′

-diphenylmethane diisocyanate, diphenyldimethylmethane diisocyanate, dibenzyl diisocyanate, naphthylene diisocyanate, phenylene diisocyanate, xylylene diisocyanate, 4,4′

-oxybis(phenyl isocyanate), 2,4,6-trimethyl-1,3-phenylene diisocyanate, tetramethylxylylene diisocyanate, tetramethylene diisocyanate, hexamethylene diisocyanate, lysine diisocyanate, 2-methylpentane-1,5-diisocyanate, 3-methylpentane-1,5-diisocyanate, hexane-1,6-diisocyanate, 2,2,4-trimethylhexamethylene diisocyanate, isophorone diisocyanate, cyclohexane diisocyanate, hydrogenated xylylene diisocyanate, hydrogenated diphenylmethane diisocyanate, hydrogenated trimethylxylylene diisocyanate, and combinations thereof.

18. The method of claim 15, wherein the polyalkylene oxide is selected from the group consisting of polyethylene glycols, polypropylene glycols, polyethylene oxides, polypropylene oxides, polyethylene glycols with lactide linkages, polypropylene glycol-co-polyethylene oxide copolymers, polyethylene oxide/polypropylene oxide copolymers, and combinations thereof.

19. The method of claim 15, wherein the anhydride is selected from the group consisting of succinic anhydride, glutaric anhydride, phthalic anhydride, maleic anhydride, and combinations thereof.

20. A method comprising:

providing a polyol possessing a functionality of at least 3;

contacting the polyol with a diisocyanate to form an isocyanate functionalized polyol;

contacting the isocyanate functionalized polyol with a polyalkylene oxide to form a polyalkylene oxide capped polyol;

contacting the polyalkylene oxide capped polyol with an anhydride to form a carboxylic acid group at the terminus of the polyalkylene oxide; and

reacting the carboxylic acid group at the terminus of the polyalkylene oxide with N-hydroxysuccinimide.

21. The method of claim 20, wherein the polyol is selected from the group consisting of polyether polyols, polyester polyols, branched chain ethoxylated alcohols, alkoxylated alcohols, polyvinyl alcohols, polyhydric alcohols, carboxylic acid esters of polyhydric alcohols, polyglycols, polylactone polyols, and combinations thereof.

22. The method of claim 20, wherein the diisocyanate is selected from the group consisting of 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, 2,2′

-diphenylmethane diisocyanate, 2,4′

-diphenylmethane diisocyanate, 4,4′

-diphenylmethane diisocyanate, diphenyldimethylmethane diisocyanate, dibenzyl diisocyanate, naphthylene diisocyanate, phenylene diisocyanate, xylylene diisocyanate, 4,4′

-oxybis(phenyl isocyanate), 2,4,6-trimethyl-1,3-phenylene diisocyanate, tetramethylxylylene diisocyanate, tetramethylene diisocyanate, hexamethylene diisocyanate, lysine diisocyanate, 2-methylpentane-1,5-diisocyanate, 3-methylpentane-1,5-diisocyanate, hexane-1,6-diisocyanate, 2,2,4-trimethylhexamethylene diisocyanate, isophorone diisocyanate, cyclohexane diisocyanate, hydrogenated xylylene diisocyanate, hydrogenated diphenylmethane diisocyanate, hydrogenated trimethylxylylene diisocyanate, and combinations thereof.

23. The method of claim 20, wherein the polyalkylene oxide is selected from the group consisting of polyethylene glycols, polypropylene glycols, polyethylene oxides, polypropylene oxides, polyethylene glycols with lactide linkages, polypropylene glycol-co-polyethylene oxide copolymers, polyethylene oxide/polypropylene oxide copolymers, and combinations thereof.

24. The method of claim 20, wherein the anhydride is selected from the group consisting of succinic anhydride, glutaric anhydride, phthalic anhydride, maleic anhydride, and combinations thereof.