Polymer-based tissue-adhesive form medical use

• US 20060079599A1
• Filed: 10/05/2005
• Published: 04/13/2006
• Est. Priority Date: 10/07/2004
• Status: Active Grant

• Current Assignee: Actamax Surgical Materials, LLC (DSM-Firmenich AG)
• Original Assignee: Actamax Surgical Materials, LLC (DSM-Firmenich AG)
• Inventors: Arthur, Samuel David
• Granted Patent: US 8,790,632 B2
• Time in Patent Office: Days
• US Class Current: 523/118
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence

Abstract

Tissue adhesives formed by reacting poly(hydroxylic) compounds derivatized with acetoacetate groups and/or polyamino compounds derivatized with acetoacetamide groups with an amino-functional crosslinking compound are disclosed. The use of the tissue adhesives for medical and veterinary applications such as topical wound closure; and surgical procedures, such as intestinal anastomosis, vascular anastomosis, tissue repair, and ophthalmic procedures; drug delivery; and anti-adhesive applications are described.

Claims

1. A kit comprising:

a) a first component comprising;

a first aqueous solution comprising at least one material selected from the group consisting of

at least one linear or branched poly(ether) derivatized with acetoacetate groups;

at least one polysaccharide derivatized with acetoacetate groups wherein said polysaccharide is other than starch, starch derivatives, cellulose, and cellulose derivatives;

at least one low molecular weight polyol derivatized with acetoacetate groups wherein said polyol has at least two hydroxy groups and has a molecular weight of less than about 300 Daltons;

at least one hydrolyzed polyvinyl acetate-methyl acrylate copolymer derivatized with acetoacetate groups;

at least one monosaccharide derivatized with acetoacetate groups;

at least one reduced monosaccharide derivatized with acetoacetate groups;

at least one polyether condensation product derivatized with acetoacetate groups wherein said polyether condensation product is produced by reacting at least one core molecule bearing more than one carboxylic acid group thereon with a sufficient amount of at least one polyether terminated with hydroxy groups to produce an esterified polyether with an average of at least two hydroxy end groups;

at least one first polyamino compound derivatized with acetoacetamide groups; and

mixtures thereof;

said material each having a weight-average molecular weight of less than about 200,000 Daltons, and an equivalent weight per acetoacetate group or acetoacetamide group of about 100 to about 2000 Daltons;

said first aqueous solution containing at least about 5% by weight of said material; and

b) a second component comprising;

at least one of

(i) a second aqueous solution of at least one second polyamino compound that may be the same or different from said first polyamino compound;

(ii) at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane, neat, or in aqueous solution; and

(iii) an aqueous solution of said at least one second polyamino compound and at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane;

wherein said at least one second polyamino compound has an equivalent weight per amino group of about 100 to about 1,000 Daltons, and said second aqueous solution contains from about 5% to about 50% by weight of said at least one second polyamino compound;

provided that if said second component is (i), then said kit may further comprise a third component comprising at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane, neat, or in aqueous solution; and

(c) optionally, a fourth component comprising an aqueous solution comprising an oxidized polysaccharide containing aldehyde groups, having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons, said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, said solution containing from about 2% to about 40% by weight of the oxidized polysaccharide.

2. A kit as recited in claim 1, wherein said at least one linear or branched poly(ether) is selected from the group consisting of linear or branched poly(ethylene oxide), linear or branched poly(propylene oxide), linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), linear or branched poly(1,3-trimethylene oxide), linear or branched poly(1,4-tetramethylene oxide), star poly(ethylene oxide), comb poly(ethylene oxide), star poly(propylene oxide), comb poly(propylene oxide), and mixtures thereof.

3. A kit as recited in claim 1, wherein said at least one polysaccharide is selected from the group consisting of dextran, agar, alginic acid, hyaluronic acid, sucrose, maltose, lactose, raffinose, and mixtures thereof.

4. A kit as recited in claim 1, wherein the methyl acrylate content in said at least one hydrolyzed polyvinyl acetate-methyl acrylate copolymer is from about 1% to about 20% by weight of said copolymer.

5. A kit as recited in claim 1, wherein said at least one monosaccharide is selected from the group consisting of ribose, glucose, mannose, galactose, fructose, sorbose, and mixtures thereof.

6. A kit as recited in claim 1, wherein said at least one reduced monosaccharide is selected from the group consisting of sorbitol, mannitol, iditol, dulcitol, and mixtures thereof.

7. A kit as recited in claim 1, wherein said carboxylic acid group in said at least one core molecule bearing more than one carboxylic acid group is selected from the group consisting of oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, benzenedicarboxylic acid, benzenetricarboxylic acid, benzenetetracarboxylic acid, cyclohexanetricarboxylic acid, cyclopentanetetracarboxylic acid, adamantanetetracarboxylic acid, biphenyltetracarboxylic acid, benzophenonetetracarboxylic acid, propanetricarboxylic acid, butanetetracarboxylic acid, and mixtures thereof.

8. A kit as recited in claim 1, wherein said at least one first polyamino compound is selected from the group consisting of amino-terminated linear or branched poly(ethylene oxide), amino-terminated linear or branched poly(propylene oxide), amino-terminated linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), amino-terminated linear or branched poly(1,3-trimethylene oxide), amino-terminated linear or branched poly(1,4-tetramethylene oxide), amino-terminated star poly(ethylene oxide), amino-terminated comb poly(ethylene oxide), amino-terminated star poly(propylene oxide), amino-terminated comb poly(propylene oxide), and mixtures thereof.

9. A kit as recited in claim 1, wherein said at least one second polyamino compound is selected from the group consisting of amino-terminated linear or branched poly(ethylene oxide), amino-terminated linear or branched poly(propylene oxide), amino-terminated linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), amino-terminated linear or branched poly(1,3-trimethylene oxide), amino-terminated linear or branched poly(1,4-tetramethylene oxide), amino-terminated star poly(ethylene oxide), amino-terminated comb poly(ethylene oxide), amino-terminated star poly(propylene oxide), amino-terminated comb poly(propylene oxide), linear or branched poly(ethyleneimine), poly(allylamine), poly(lysine), poly(vinyl alcohol) derivatized with 4-aminobutyral acetal groups, linear or branched diaminoalkanes in the weight average molecular weight range of from about 80 Daltons to about 300 Daltons, 4,9-dioxa-1,12-dodecanediamine, N,N′

-bis(3-aminopropyl)piperazine, 5-amino-1,3,3-trimethylcyclohexanemethylamine, 1,3-bis(aminomethyl)cyclohexane, 1,4-diaminocyclohexane, xylylenediamine, adipic dihydrazide, (hydrazidocarboxymethyl)-terminated linear or branched poly(ethylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(propylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(ethylene oxide)-poly(propylene oxide) copolymer, (hydrazidocarboxymethyl)-terminated linear or branched poly(1,3-trimethylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(1,4-tetramethylene oxide), spermine, spermidine, dendrimeric amino-terminated copoly(ethylenediaminetetrapropionic acid-ethylenediamine) poly(amidoamines), and mixtures thereof.

10. A kit as recited in claim 1, wherein said at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane in said second component is selected from the group consisting of 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-aminopropyltripropoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, 3-aminopropyldimethoxymethylsilane, 3-aminopropyldiethoxymethylsilane, 3-aminopropyldipropoxymethylsilane, 3-aminopropyldimethoxyethylsilane, 3-aminopropyldiethoxyethylsilane, 3-(methoxydimethylsilyl)propylamine, 3-(ethoxydimethylsilyl)propylamine and mixtures thereof.

11. A kit as recited in claim 1, wherein said at least one linear or branched poly(ether) has a weight-average molecular weight in the range of from about 500 Daltons to about 20,000 Daltons.

12. A kit as recited in claim 1, wherein said at least one polysaccharide has a weight-average molecular weight in the range of from about 10,000 Daltons to about 100,000 Daltons

13. A kit as recited in claim 1, wherein said at least one hydrolyzed polyvinyl acetate-methyl acrylate copolymer has a weight-average molecular weight in the range of from about 20,000 Daltons to about 80,000 Daltons.

14. A kit as recited in claim 1, wherein said first and second aqueous solutions have a water content in the range of from about 70% to about 85% by weight relative to the total weight of the aqueous solutions.

15. The kit as recited in claim 1, wherein said aqueous solutions and said at least one neat 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane are sterilized.

16. The kit as recited in claim 1, wherein at least one of said aqueous solutions further comprises an additive selected from the group consisting of pH modifiers, viscosity modifiers, antimicrobials, colorants, healing promoters, surfactants, anti-inflammatory agents, thrombogenic agents, and radio-opaque compounds.

17. The kit as recited in claim 16 wherein said colorants are selected from the group consisting of FD&

C Violet No. 2, D&

C Green No. 6, D&

C Green No. 5, and D&

C Violet No. 2.

18. The kit as recited in claim 16 wherein said antimicrobial is triclosan.

19. The kit as recited in claim 1, wherein the concentration of said second polyamino compound in said second aqueous solution is about 15% to about 30% by weight.

20. The kit as recited in claim 1, wherein the weight-average molecular weight of said oxidized polysaccharide is from about 3,000 to about 250,000 Daltons.

21. The kit as recited in claim 1, wherein said oxidized polysaccharide is selected from the group consisting of dextran, chitin, starch, agar, cellulose, and hyaluronic acid.

22. The kit as recited in claim 1, wherein said low molecular weight polyol is selected from the group consisting of glycerol, trimethylolpropane, pentaerythritol, dipentaerythritol and mixtures thereof.

23. The kit as recited in claim 1, wherein said first aqueous solution further comprises at least one oxidized polysaccharide containing aldehyde groups, having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons, said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, said solution containing from about 2% to about 20% by weight of the oxidized polysaccharide.

24. The kit as recited in claim 23, wherein said oxidized polysaccharide is selected from the group consisting of dextran, chitin, starch, agar, cellulose, and hyaluronic acid.

25. A method for applying a coating to an anatomical site on tissue of a living organism comprising:

(a) optionally priming said anatomical site with an aqueous solution comprising an oxidized polysaccharide containing aldehyde groups, having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons, said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, said solution containing from about 2% to about 40% by weight of the oxidized polysaccharide;

(b) applying to said anatomical site a first component comprising an aqueous solution comprising

(i) at least one poly(hydroxylic) compound derivatized with acetoacetate groups and/or

(ii) a first polyamino compound derivatized with acetoacetamide groups,

each of (i) or (ii) having a weight-average molecular weight of less than about 200,000 Daltons and having an equivalent weight per acetoacetate group or acetoacetamide group, respectively, of about 100 to about 2000 Daltons; and

(c) applying to said anatomical site a second component comprising at least one of

(iii) an aqueous solution of at least one second polyamino compound that may be same or different from said first polyamino compound,

(iv) at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane, neat or in aqueous solution, and

(v) an aqueous solution of at least one second polyamino compound and at least one 3-aminopropyltrialkoxysilane, 3aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane, wherein said at least one second polyamino compound has an equivalent weight per amino group of about 100 to about 1,000 Daltons; and

(d) mixing said components on the surface of said anatomical site;

or

(e) applying said second component to said anatomical site, followed by said first component, followed by mixing the solutions on the surface of said anatomical site;

or

(f) premixing said first and second components, and applying the resulting mixture to said anatomical site before said resulting mixture completely cures;

provided that a third component comprising at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane, neat or in aqueous solution, may be applied to said anatomical site at substantially the same time as said second component is applied to said anatomical site.

26. The method as recited in claim 25, wherein said first polyamino compound is selected from group consisting of amino-terminated linear or branched poly(ethylene oxide), amino-terminated linear or branched poly(propylene oxide), amino-terminated linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), amino-terminated linear or branched poly(1,3-trimethylene oxide), amino-terminated linear or branched poly(1,4-tetramethylene oxide), amino-terminated star poly(ethylene oxide), amino-terminated comb poly(ethylene oxide), amino-terminated star poly(propylene oxide), amino-terminated comb poly(propylene oxide), and mixtures thereof.

27. The method as recited in claim 25, wherein said at least one poly(hydroxylic) compound derivatized with acetoacetate groups is selected from the group consisting of

at least one poly(vinyl alcohol) derivatized with acetoacetate groups;

at least one poly(vinyl alcohol) copolymer derivatized with acetoacetate groups wherein said poly(vinyl alcohol) copolymer comprises between about 1 mole percent and about 25 mole percent of the comonomer relative to the vinyl alcohol units;

at least one linear or branched poly(ether) derivatized with acetoacetate groups;

at least one polysaccharide derivatized with acetoacetate groups;

at least one low molecular weight polyol derivatized with acetoacetate groups wherein said polyol has at least two hydroxy groups and has a molecular weight of less than about 300 Daltons;

at least one hydrolyzed polyvinyl acetate-methyl acrylate copolymer derivatized with acetoacetate groups;

at least one monosaccharide derivatized with acetoacetate groups;

at least one reduced monosaccharide derivatized with acetoacetate groups;

at least one polyether condensation product derivatized with acetoacetate groups wherein said polyether condensation product is produced by reacting at least one core molecule bearing more than one carboxylic acid group thereon with a sufficient amount of at least one polyether terminated with hydroxy groups to produce an esterified polyether with an average of at least two hydroxy end groups;

and mixtures thereof.

28. The method as recited in claim 27, wherein said poly(vinyl alcohol) has a weight-average molecular weight in the range of from about 10,000 Daltons to about 50,000 Daltons

29. The method as recited in claim 27, wherein the degree of hydrolysis of said poly(vinyl alcohol) is from about 60% to about 100%, the balance being acetate groups.

30. The method as recited in claim 27, wherein said poly(vinyl alcohol) copolymer comprises a comonomer selected from the group consisting of ethylene, methyl acrylate, methyl methacrylate, acrylic acid, itaconic acid, maleic acid, fumaric acid, methyl vinyl ether, propylene, 1-butene, and mixtures thereof.

31. The method as recited in claim 25, wherein said at least one second polyamino compound is selected from the group consisting of amino-terminated linear or branched poly(ethylene oxide), amino-terminated linear or branched poly(propylene oxide), amino-terminated linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), amino-terminated linear or branched poly(1,3-trimethylene oxide), amino-terminated linear or branched poly(1,4-tetramethylene oxide), amino-terminated star poly(ethylene oxide), amino-terminated comb poly(ethylene oxide), amino-terminated star poly(propylene oxide), amino-terminated comb poly(propylene oxide), linear or branched poly(ethyleneimine), poly(allylamine), poly(lysine), poly(vinyl alcohol) derivatized with 4-aminobutyral acetal groups, poly(vinyl alcohol-co-vinylamine), linear or branched diaminoalkanes in the weight average molecular weight range of from about 80 Daltons to about 300 Daltons, 4,9-dioxa-1,12-dodecanediamine, N,N′

-bis(3-aminopropyl)piperazine, 5-amino-1,3,3-trimethylcyclohexanemethylamine, 1,3-bis(aminomethyl)cyclohexane, 1,4-diaminocyclohexane, xylylenediamine, adipic dihydrazide, (hydrazidocarboxymethyl)-terminated linear or branched poly(ethylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(propylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(ethylene oxide)-poly(propylene oxide) copolymer, (hydrazidocarboxymethyl)-terminated linear or branched poly(1,3-trimethylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(1,4-tetramethylene oxide), spermine, spermidine, dendrimeric amino-terminated copoly(ethylenediaminetetrapropionic acid-ethylenediamine) poly(amidoamines), and mixtures thereof.

32. The method as recited in claim 25, wherein the concentration of poly(hydroxylic) compound derivatized with acetoacetate groups in the aqueous solution of (b) is from about 15% to about 30% by weight.

33. The method as recited in claim 25, wherein the concentration of said second polyamino compound in the aqueous solution of (c) is about 15% to about 30% by weight.

34. The method as recited in claim 25, wherein the weight-average molecular weight of said oxidized polysaccharide is from about 3,000 to about 250,000 Daltons.

35. The method as recited in claim 25, wherein said oxidized polysaccharide is selected from the group consisting of dextran, chitin, starch, agar, cellulose, and hyaluronic acid.

36. The method as recited in claim 25, wherein said aqueous solutions and said at least one neat 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane are sterilized.

37. The method as recited in claim 25, wherein said aqueous solution of (b) further comprises at least one oxidized polysaccharide containing aldehyde groups, having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons, said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, said solution containing from about 2% to about 20% by weight of the oxidized polysaccharide.

38. The method as recited in claim 37, wherein said oxidized polysaccharide is selected from the group consisting of dextran, chitin, starch, agar, cellulose, and hyaluronic acid.

39. The method as recited in claim 25 wherein said anatomical site is a wound on the skin and the method is used for treatment of topical wounds.

40. The method as recited in claim 25 wherein said anatomical site is on an intestine or blood vessel and the method is used in an anastomosis procedure.

41. The method as recited in claim 25 wherein said anatomical site is on the eye and the method is used to seal a corneal incision.

42. The method as recited in claim 25 wherein said method is used to prevent adhesions between adjacent anatomical sites.

43. The method as recited in claim 25 wherein at least one of said aqueous solutions further comprises a pharmaceutical drug or therapeutic agent and said method is used for drug delivery to the anatomical site.

44. A method for bonding at least two anatomical sites together comprising:

(a) optionally priming at least one anatomical site with an aqueous solution comprising an oxidized polysaccharide containing aldehyde groups, having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons, said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, said solution containing from about 2% to about 40% by weight of the oxidized polysaccharide;

(b) applying a first component to at least one anatomical site comprising an aqueous solution comprising

(i) at least one poly(hydroxylic) compound derivatized with acetoacetate groups and/or

(ii) a first polyamino compound derivatized with acetoacetamide groups,

each of (i) or (ii) having a weight-average molecular weight of less than about 200,000 Daltons and having an equivalent weight per acetoacetate group or acetoacetamide group, respectively, of about 100 to about 2000 Daltons;

(c) applying to said at least one anatomical site a second component comprising at least one of

(iii) an aqueous solution of at least one second polyamino compound that may be same or different from said first polyamino compound;

(iv) at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane, neat or in aqueous solution; and

(v) an aqueous solution of at least one polyamino compound and at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane, wherein said polyamino compound has an equivalent weight per amino group of about 100 to about 1,000 Daltons;

(d) mixing said components on the surface of said at least one anatomical site;

or

(e) applying said second component to said at least one anatomical site, followed by said first component, followed by mixing the solutions on the surface of said at least one anatomical site;

or

(f) premixing said first and second components, and applying the resulting mixture to said at least one anatomical site before said resulting mixture completely cures;

provided that a third component comprising at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane, neat or in aqueous solution, may be applied to said at least one anatomical site at substantially the same time as said second component is applied to said at least one anatomical site; and

(g) contacting said at least two anatomical sites together.

45. The method as recited in claim 44, wherein said first polyamino compound is selected from group consisting of amino-terminated linear or branched poly(ethylene oxide), amino-terminated linear or branched poly(propylene oxide), amino-terminated linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), amino-terminated linear or branched poly(1,3-trimethylene oxide), amino-terminated linear or branched poly(1,4-tetramethylene oxide), amino-terminated star poly(ethylene oxide), amino-terminated comb poly(ethylene oxide), amino-terminated star poly(propylene oxide), amino-terminated comb poly(propylene oxide), and mixtures thereof.

46. The method as recited in claim 44, wherein said at least one poly(hydroxylic) compound derivatized with acetoacetate groups is selected from the group consisting of

at least one poly(vinyl alcohol) derivatized with acetoacetate groups;

at least one poly(vinyl alcohol) copolymer derivatized with acetoacetate groups with said vinyl alcohol) copolymer comprises between about 1 mole percent and about 25 mole percent of the comonomer relative to the vinyl alcohol units;

at least one linear or branched poly(ether) derivatized with acetoacetate groups;

at least one polysaccharide derivatized with acetoacetate groups;

at least one low molecular weight polyol derivatized with acetoacetate groups wherein said polyol has at least two hydroxy groups and has a molecular weight of less than about 300 Daltons;

at least one hydrolyzed polyvinyl acetate-methyl acrylate copolymer derivatized with acetoacetate groups;

at least one monosaccharide derivatized with acetoacetate groups;

at least one reduced monosaccharide derivatized with acetoacetate groups;

at least one polyether condensation product derivatized with acetoacetate groups wherein said polyether condensation product is produced by reacting at least one core molecule bearing more than one carboxylic acid group thereon with a sufficient amount of at least one polyether terminated with hydroxy groups to produce an esterified polyether with an average of at least two hydroxy end groups; and

mixtures thereof.

47. The method as recited in claim 46, wherein said poly(vinyl alcohol) copolymer comprises a comonomer selected from the group consisting of ethylene, methyl acrylate, methyl methacrylate, acrylic acid, itaconic acid, maleic acid, fumaric acid, methyl vinyl ether, propylene, 1-butene, and mixtures thereof.

48. The method as recited in claim 46, wherein poly(vinyl alcohol) has a weight-average molecular weight in the range of from about 10,000 Daltons to about 50,000 Daltons

49. The method as recited in claim 46, wherein the degree of hydrolysis of said poly(vinyl alcohol) is from about 60% to about 100%, the balance being acetate groups.

50. The method as recited in claim 44, wherein said second polyamino compound is selected from the group consisting of amino-terminated linear or branched poly(ethylene oxide), amino-terminated linear or branched poly(propylene oxide), amino-terminated linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), amino-terminated linear or branched poly(1,3-trimethylene oxide), amino-terminated linear or branched poly(1,4-tetramethylene oxide), amino-terminated star poly(ethylene oxide), amino-terminated comb poly(ethylene oxide), amino-terminated star poly(propylene oxide), amino-terminated comb poly(propylene oxide), linear or branched poly(ethyleneimine), poly(allylamine), poly(lysine), poly(vinyl alcohol) derivatized with 4-aminobutyral acetal groups, poly(vinyl alcohol-co-vinylamine), linear or branched diaminoalkanes in the weight average molecular weight range of from about 80 Daltons to about 300 Daltons, 4,9-dioxa-1,12-dodecanediamine, N,N′

-bis(3-aminopropyl)piperazine, 5-amino-1,3,3-trimethylcyclohexanemethylamine, 1,3-bis(aminomethyl)cyclohexane, 1,4-diaminocyclohexane, xylylenediamine, adipic dihydrazide, (hydrazidocarboxymethyl)-terminated linear or branched poly(ethylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(propylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(ethylene oxide)-poly(propylene oxide) copolymer, (hydrazidocarboxymethyl)-terminated linear or branched poly(1,3-trimethylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(1,4-tetramethylene oxide), spermine, spermidine, dendrimeric amino-terminated copoly(ethylenediaminetetrapropionic acid-ethylenediamine) poly(amidoamines), and mixtures thereof.

51. The method as recited in claim 44, wherein the concentration of the poly(hydroxylic) compound derivatized with acetoacetate groups in the aqueous solution of (b) is from about 15% to about 30% by weight.

52. The method as recited in claim 44, wherein the concentration of said second polyamino compound in the aqueous solution of (c) is about 15% to about 30% by weight.

53. The method as recited in claim 44, wherein said aqueous solution of (b) further comprises at least one oxidized polysaccharide containing aldehyde groups, having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons, said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, said solution containing from about 2% to about 20% by weight of the oxidized polysaccharide.

54. The method as recited in claim 53, wherein said oxidized polysaccharide is selected from the group consisting of dextran, chitin, starch, agar, cellulose, and hyaluronic acid.

55. A composition comprising the reaction product of:

a) a first component comprising;

a first aqueous solution comprising at least one material selected from the group consisting of

at least one linear or branched poly(ether) derivatized with acetoacetate groups;

at least one polysaccharide derivatized with acetoacetate groups wherein said polysaccharide is other than starch, starch derivatives, cellulose, and cellulose derivatives;

at least one low molecular weight polyol derivatized with acetoacetate groups wherein said polyol has at least two hydroxy groups and has a molecular weight of less than 300 Daltons;

at least one hydrolyzed polyvinyl acetate-methyl acrylate copolymer derivatized with acetoacetate groups;

at least one monosaccharide derivatized with acetoacetate groups;

at least one reduced monosaccharide derivatized with acetoacetate groups;

at least one polyether condensation product derivatized with acetoacetate groups wherein said polyether condensation product is produced by reacting at least one core molecule bearing more than one carboxylic acid group thereon with a sufficient amount of at least one polyether terminated with hydroxy groups to produce an esterified polyether with an average of at least two hydroxy end groups;

at least one first polyamino compound derivatized with acetoacetamide groups; and

mixtures thereof;

said material each having a weight-average molecular weight less than about 200,000 Daltons, and an equivalent weight per acetoacetate group or acetoacetamide group of about 100 to about 2000 Daltons;

said first aqueous solution containing at least about 5% by weight of said material; and

b) a second component comprising;

at least one of

(i) a second aqueous solution of at least one second polyamino compound that may be the same or different from said first polyamino compound;

(ii) at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane, neat, or in aqueous solution; and

(iii) an aqueous solution of said at least one second polyamino compound, and at least one 3-aminopropyltrialkoxysilane, 3aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane;

wherein said at least one second polyamino compound has an equivalent weight per amino group of about 100 to about 1,000 Daltons, and said second aqueous solution contains from about 5% to about 50% by weight of said at least one second polyamino compound;

provided that if said second component is (i), then said kit may further comprise a third component comprising at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane, neat, or in aqueous solution; and

(c) optionally, a fourth component comprising an aqueous solution comprising an oxidized polysaccharide containing aldehyde groups, having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons, said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, said solution containing from about 2% to about 40% by weight of the oxidized polysaccharide.

56. A composition as recited in claim 55, wherein said at least one linear or branched poly(ether) is selected from the group consisting of linear or branched poly(ethylene oxide), linear or branched poly(propylene oxide), linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), linear or branched poly(1,3-trimethylene oxide), linear or branched poly(1,4-tetramethylene oxide), star poly(ethylene oxide), comb poly(ethylene oxide), star poly(propylene oxide), comb poly(propylene oxide), and mixtures thereof.

57. A composition as recited in claim 55, wherein said at least one polysaccharide is selected from the group consisting of dextran, agar, alginic acid, hyaluronic acid, sucrose, maltose, lactose, raffinose, and mixtures thereof.

58. A composition as recited in claim 55, wherein the methyl acrylate content in said at least one hydrolyzed polyvinyl acetate-methyl acrylate copolymer is from about 1% to about 20% by weight of said copolymer.

59. A composition as recited in claim 55, wherein said at least one monosaccharide is selected from the group consisting of ribose, glucose, mannose, galactose, fructose, sorbose, and mixtures thereof.

60. A composition as recited in claim 55, wherein said at least one reduced monosaccharide is selected from the group consisting of sorbitol, mannitol, iditol, dulcitol, and mixtures thereof.

61. A composition as recited in claim 55, wherein said carboxylic acid group in said at least one core molecule bearing more than one carboxylic acid group is selected from the group consisting of oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, benzenedicarboxylic acid, benzenetricarboxylic acid, benzenetetracarboxylic acid, cyclohexanetricarboxylic acid, cyclopentanetetracarboxylic acid, adamantanetetracarboxylic acid, biphenyltetracarboxylic acid, benzophenonetetracarboxylic acid, propanetricarboxylic acid, butanetetracarboxylic acid, and mixtures thereof.

62. A composition as recited in claim 55, wherein said at least one first polyamino compound is selected from the group consisting of amino-terminated linear or branched poly(ethylene oxide), amino-terminated linear or branched poly(propylene oxide), amino-terminated linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), amino-terminated linear or branched poly(1,3-trimethylene oxide), amino-terminated linear or branched poly(1,4-tetramethylene oxide), amino-terminated star poly(ethylene oxide), amino-terminated comb poly(ethylene oxide), amino-terminated star poly(propylene oxide), amino-terminated comb poly(propylene oxide), and mixtures thereof.

63. A composition as recited in claim 55, wherein said at least one second polyamino compound is selected from the group consisting of amino-terminated linear or branched poly(ethylene oxide), amino-terminated linear or branched poly(propylene oxide), amino-terminated linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), amino-terminated linear or branched poly(1,3-trimethylene oxide), amino-terminated linear or branched poly(1,4-tetramethylene oxide), amino-terminated star poly(ethylene oxide), amino-terminated comb poly(ethylene oxide), amino-terminated star poly(propylene oxide), amino-terminated comb poly(propylene oxide), linear or branched poly(ethyleneimine), poly(allylamine), poly(lysine), poly(vinyl alcohol) derivatized with 4-aminobutyral acetal groups, linear or branched diaminoalkanes in the weight average molecular weight range of from about 80 Daltons to about 300 Daltons, 4,9-dioxa-1,12-dodecanediamine, N,N′

-bis(3-aminopropyl)piperazine, 5-amino-1,3,3-trimethylcyclohexanemethylamine, 1,3-bis(aminomethyl)cyclohexane, 1,4-diaminocyclohexane, xylylenediamine, adipic dihydrazide, (hydrazidocarboxymethyl)-terminated linear or branched poly(ethylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(propylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(ethylene oxide)-poly(propylene oxide) copolymer, (hydrazidocarboxymethyl)-terminated linear or branched poly(1,3-trimethylene oxide), (hydrazidocarboxymethyl)-terminated linear or branched poly(1,4-tetramethylene oxide), spermine, spermidine, dendrimeric amino-terminated copoly(ethylenediaminetetrapropionic acid-ethylenediamine) poly(amidoamines), and mixtures thereof.

64. A composition as recited in claim 55, wherein said at least one 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane in said second component is selected from the group consisting of 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-aminopropyltripropoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, 3-aminopropyldimethoxymethylsilane, 3-aminopropyldiethoxymethylsilane, 3-aminopropyldipropoxymethylsilane, 3-aminopropyldimethoxyethylsilane, and 3-aminopropyldiethoxyethylsilane, 3-(methoxydimethylsilyl)propylamine, 3-(ethoxydimethylsilyl)propylamine and mixtures thereof.

65. A composition as recited in claim 55, wherein said at least one linear or branched poly(ether) has a weight-average molecular weight in the range of from about 500 Daltons to about 20,000 Daltons.

66. A composition as recited in claim 55, wherein said at least one polysaccharide has a weight-average molecular weight in the range of from about 10,000 Daltons to about 100,000 Daltons.

67. A composition as recited in claim 55, wherein said at least one hydrolyzed polyvinyl acetate-methyl acrylate copolymer has a weight-average molecular weight in the range of from about 20,000 Daltons to about 80,000 Daltons.

68. A composition as recited in claim 55, wherein said first and second aqueous solutions have a water content in the range of from about 70% to about 85% by weight of the total weight of the aqueous solutions.

69. The composition as recited in claim 55, wherein said aqueous solutions and said at least one neat 3-aminopropyltrialkoxysilane, 3-aminopropyldialkoxyalkylsilane or 3-aminopropylmonoalkoxydialkylsilane are sterilized.

70. The composition as recited in claim 55, wherein at least one of said aqueous solutions further comprises an additive selected from the group consisting of pH modifiers, viscosity modifiers, antimicrobials, colorants, healing promoters, surfactants, anti-inflammatory agents, thrombogenic agents, and radio-opaque compounds.

71. The composition as recited in claim 70 wherein said colorants are selected from the group consisting of FD&

C Violet No. 2, D&

C Green. No. 6, D&

C Green No. 5, and D&

C Violet No. 2.

72. The composition as recited in claim 70 wherein said animicrobial is triclosan.

73. The composition as recited in claim 55, wherein the concentration of said second polyamino compound in said second aqueous solution is about 15% to about 30% by weight.

74. The composition as recited in claim 55, wherein the weight-average molecular weight of said oxidized polysaccharide is from about 3,000 to about 250,000 Daltons.

75. The composition as recited in claim 55, wherein said oxidized polysaccharide is selected from the group consisting of dextran, chitin, starch, agar, cellulose, and hyaluronic acid.

76. The composition as recited in claim 55, wherein said low molecular weight polyol

is selected from the group consisting of glycerol, trimethylolpropane, pentaerythritol, dipentaerythritol and mixtures thereof.

77. The composition as recited in claim 55, wherein said first aqueous solution further comprises at least one oxidized polysaccharide containing aldehyde groups, having a weight-average molecular weight of about 1,000 to about 1,000,000 Daltons, said oxidized polysaccharide having an equivalent weight per aldehyde group of about 90 to about 1500 Daltons, said solution containing from about 2% to about 20% by weight of the oxidized polysaccharide.

78. The composition as recited in claim 77, wherein said oxidized polysaccharide is selected from the group consisting of dextran, chitin, starch, agar, cellulose, and hyaluronic acid.

79. A composition comprising dextran derivatized with acetoacetate groups, wherein said dextran derivatized with acetoacetate groups has a weight-average molecular weight of about 500 to about 200,000 Daltons, and an equivalent weight per acetoacetate group of about 100 to about 2,000 Daltons.

80. A composition comprising a linear or branched polyether derivatized with acetoacetate groups wherein said linear or branched polyether derivatized with acetoacetate groups has a weight-average molecular weight of about 500 to about 200,000 Daltons, and an equivalent weight per acetoacetate group of about 100 to about 2,000 Daltons.

81. The composition as recited in claim 80 wherein said linear or branched poly(ether) is selected from the group consisting of linear or branched poly(ethylene oxide), linear or branched poly(propylene oxide), linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), linear or branched poly(1,3-trimethylene oxide), linear or branched poly(1,4-tetramethylene oxide), star poly(ethylene oxide), comb poly(ethylene oxide), star poly(propylene oxide), comb poly(propylene oxide), and mixtures thereof.

82. A composition comprising a polyamino compound derivatized with acetoacetamide groups wherein said polyamino compound derivatized with acetoacetamide groups has a weight-average molecular weight of about 500 to about 200,000 Daltons, and an equivalent weight per acetoacetate group of about 100 to about 2,000 Daltons.

83. The composition as recited in claim 82 wherein said polyamino compound derivatized with acetoacetamide groups is selected from the group consisting of amino-terminated linear or branched poly(ethylene oxide), amino-terminated linear or branched poly(propylene oxide), amino-terminated linear or branched copolymers of poly(ethylene oxide) and poly(propylene oxide), amino-terminated linear or branched poly(1,3-trimethylene oxide), amino-terminated linear or branched poly(1,4-tetramethylene oxide), amino-terminated star poly(ethylene oxide), amino-terminated comb poly(ethylene oxide), amino-terminated star poly(propylene oxide), amino-terminated comb poly(propylene oxide), and mixtures thereof.

84. A composition comprising a polyether condensation product derivatized with acetoacetate groups, wherein said polyether condensation product is produced by reacting at least one core molecule bearing more than one carboxylic acid group thereon with a sufficient amount of at least one polyether terminated with hydroxy groups to produce an esterified polyether with an average of at least two hydroxy end groups and wherein said polyether condensation product derivatized with acetoacetate groups has a weight-average molecular weight of about 500 to about 200,000 Daltons, and an equivalent weight per acetoacetate group of about 100 to about 2,000 Daltons.

85. The composition as recited in claim 84, wherein said carboxylic acid group in said at least one core molecule bearing more than one carboxylic acid group is selected from the group consisting of oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, benzenedicarboxylic acid, benzenetricarboxylic acid, benzenetetracarboxylic acid, cyclohexanetricarboxylic acid, cyclopentanetetracarboxylic acid, adamantanetetracarboxylic acid, biphenyltetracarboxylic acid, benzophenonetetracarboxylic acid, propanetricarboxylic acid, butanetetracarboxylic acid, and mixtures thereof.

86. A composition comprising a monosaccharide derivatized with acetoacetate groups, wherein said monosaccharide derivatized with acetoacetate groups has an equivalent weight per acetoacetate group of about 100 to about 200 Daltons.

87. The composition as recited in claim 86 wherein said monosaccharide is selected from the group consisting of ribose, glucose, mannose, galactose, fructose, sorbose, and mixtures thereof.

88. A composition comprising a reduced monosaccharide derivatized with acetoacetate groups wherein said reduced monosaccharide derivatized with acetoacetate groups has an equivalent weight per acetoacetate group of about 100 to about 200 Daltons.

89. The composition as recited in claim 88 wherein the reduced monosaccharide is selected from the group consisting of sorbitol, mannitol, iditol, dulcitol, and mixtures thereof.

90. A composition comprising a low molecular weight polyol derivatized with acetoacetate groups wherein said polyol has at least two hydroxy groups and has a molecular weight of less than 300 Daltons, and an equivalent weight per acetoacetate group of about 100 to about 200 Daltons.

91. The composition as recited in claim 90, wherein said polyol is selected from the group consisting of glycerol, trimethylolpropane, pentaerythritol, dipentaerythritol and mixtures thereof.

92. A composition comprising a hydrolyzed polyvinylacetate-methyl acrylate copolymer derivatized with acetoacetate groups, wherein said hydrolyzed polyvinylacetate-methyl acrylate copolymer derivatized with acetoacetate groups has a weight-average molecular weight of about 500 to about 200,000 Daltons, and an equivalent weight per acetoacetate group of about 100 to about 2,000 Daltons.

93. The composition as recited in claim 92 wherein said hydrolyzed polyvinyl acetate-methyl acrylate copolymer has a weight-average molecular weight in the range of from about 20,000 Daltons to about 80,000 Daltons.

94. The composition as recited in claim 93, wherein the methyl acrylate content in said hydrolyzed polyvinyl acetate-methyl acrylate copolymer is from about 1% to about 20% by weight of said copolymer.