Absorbable adhesive compositions

• US 6,620,846 B1
• Filed: 08/02/2000
• Issued: 09/16/2003
• Est. Priority Date: 08/02/2000
• Status: Expired due to Term

• Current Assignee: Ethicon Incorporated (Johnson & Johnson)
• Original Assignee: Closure Medical Corporation (Johnson & Johnson)
• Inventors: Moseley, Jon P., Quintero, Julian, Jonn, Jerry Y., Bobo, John
• Primary Examiner(s): Dees, Jose′ G.
• Assistant Examiner(s): George, Konata M.
• Application Number:
  US09/630,437
• Time in Patent Office: 1,140 Days
• Field of Search: 424/443, 424/447, 424/451, 514/519, 514/642, 514/644
• US Class Current: 514/519
• CPC Class Codes: A61L 24/06 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043, A61L24/046 take precedence
• CPC Class Codes: C08F 222/328 Alpha-cyano-acrylic acid with more than one oxygen in the ester moiety
• CPC Class Codes: C08L 35/04 Homopolymers or copolymers of nitriles C08L35/06, C08L35/08 take precedence
• CPC Class Codes: C09J 4/00 Adhesives based on organic non-macromolecular compounds having at least one polymerisable carbon-to-carbon unsaturated bond ; adhesives, based on monomers of macromolecular compounds of groups C09J183/00 - C09J183/16

Abstract

A method of treating living tissue includes applying to living tissue a biocompatible adhesive composition containing at least one alkyl ester cyanoacrylate monomer and a polymerization initiator or accelerator, wherein the polymerization initiator or accelerator is a quaternary amine.

Claims

1. A method of treating living tissue, comprising:

applying to living tissue a biocompatible adhesive composition comprising at least one alkyl ester cyanoacrylate monomer and a polymerization initiator or accelerator, wherein said polymerization initiator or accelerator is a quaternary amine,

wherein said at least one alkyl ester cyanoacrylate monomer has the formula

wherein R₁ and R₂ are independently H, a straight, branched or cyclic alkyl group, or are combined together in a cyclic alkyl group, and R₃ is a straight, branched or cyclic alkyl group.

2. The method of claim 1, wherein the polymerization initiator or accelerator is combined with the at least one monomer prior to applying the composition to living tissue.

3. The method of claim 1, wherein the polymerization initiator or accelerator is combined with the at least one monomer after the at least one monomer is applied to living tissue.

4. A The method of claim 1, wherein the at least one monomer is combined with the polymerization initiator or accelerator after the polymerization initiator or accelerator is applied to living tissue.

5. The method of claim 1, wherein R₁ is H or a C₁-C₃ alkyl group;

R₂ is H or a C₁-C₃ alkyl group; and

R₃ is a C₁-C₁₆ alkyl group.

6. The method of claim 1, wherein R₃ is a C₁-C₁₀ alkyl group.

7. The method of claim 1, wherein R₃ is a C₂-C₄ alkyl group.

8. The method of claim 1, wherein R₃ is butyl.

9. The method of claim 1, wherein the at least one alkyl ester cyanoacrylate monomer is butyl lactoyl cyanoacrylate.

10. The method of claim 1, wherein the at least one monomer is butyl glycoloyl cyanoacrylate.

11. The method of claim 1, wherein said polymerization initiator or accelerator has the following formula

wherein R₄, R₅, R₆ and R₇ are each independently H or a substituted or unsubstituted straight, branched or cyclic alkyl group; a substituted or unsubstituted aromatic group;

a substituted or unsubstituted aralkyl group;

or a substituted or unsubstituted alkyl or aromatic group containing one or more hetero atoms; and

X⁻

is an anion.

12. The method of claim 11, wherein at least one of R₄, R₅, R₆ and R₇ comprises at least one member selected from the group consisting of an aromatic ring and a hetero atom-containing linkage.

13. The method of claim 11, wherein X⁻

is a halogen radical.

14. The method of claim 1, wherein said polymerization initiator or accelerator is at least one member selected from the group consisting of domiphen bromide, butyrylcholine chloride, benzalkonium bromide, and acetyl choline chloride.

15. The method of claim 1, wherein said adhesive composition further comprises at least one component selected from the group consisting of a thickener, a plasticizer, a colorant, a preservative, a heat dissipating agent, an acidic stabilizing agent, and a formaldehyde scavenger.

16. The method of claim 11, wherein said adhesive composition further comprises at least one component selected from the group consisting of a thickener, a plasticizer, a colorant, a preservative, a heat dissipating agent, an acidic stabilizing agent, and a formaldehyde scavenger.

17. The method of claim 1, wherein said adhesive composition further comprises at least one other cyanoacrylate monomer.

18. The method of claim 1, wherein said adhesive composition has a Sterility Assurance Level (SAL) value of 10⁻

3-10<sup>−

6</sup>.

19. The method of claim 1, wherein said at least one monomer is applied in an amount of 65 to 99.9 weight % and said polymerization initiator or accelerator is applied in an amount of 0.005 to 10 weight %, based on a total weight of said composition.

20. The method of claim 1, wherein said at least one monomer is applied in an amount of 80 to 99 weight % and said polymerization initiator or accelerator is applied in an amount of 0.02 to 5 weight %, based on a total weight of said composition.

21. The method of claim 1, wherein said at least one monomer is applied in an amount of 85 to 99 weight % and said polymerization initiator or accelerator is applied in an amount of 0.05 to 3 weight %, based on a total weight of said composition.

22. The method of claim 1, wherein the method is used to close or seal a wound.

23. The method of claim 1, wherein the method is used to close or seal a wound in internal tissue.

24. The method of claim 1, further comprising suturing or stapling said tissue before or after applying said biocompatible adhesive composition to said tissue.

25. The method of claim 1, wherein said tissue is a blood vessel.

71. The method of claim 1, wherein a polymer formed from said biocompatible adhesive composition is absorbed by said living tissue in a period of less than two years after application to the living tissue.

72. The method of claim 1, wherein said polymerization initiator or accelerator polymerizes said at least one alkyl ester cyanoacrylate monomer in less than 3 minutes.

26. A kit comprising a saleable package comprising:

a first container that contains a biocompatible adhesive composition comprising at least one alkyl ester cyanoacrylate monomer; and

a polymerization initiator or accelerator, wherein said polymerization initiator or accelerator is a quaternary amine,

wherein said at least one alkyl ester cyanoacrylate monomer has the formula

wherein R₁ and R₂ are independently H, a straight, branched or cyclic alkyl group, or are combined together in a cyclic alkyl group, and R₃ is a straight, branched or cyclic alkyl group.

27. The kit of claim 27, wherein said polymerization initiator or accelerator is contained in a second container.

28. The kit of claim 27, wherein said polymerization initiator or accelerator is contained in the first container, but not in contact with said at least one monomer.

29. The kit of claim 27, wherein said at least one monomer is contained in a first frangible ampoule and said polymerization initiator or accelerator is contained in a second frangible ampoule.

30. The kit of claim 27, wherein said polymerization initiator or accelerator is contained in a tip of said first container.

31. The kit of claim 27, further comprising at least one member selected from the group consisting of a brush, swab and sponge.

32. The kit of claim 27, wherein R₁ is H or a C₁-C₃ alkyl group;

R₂ is H or a C₁-C₃ alkyl group; and

R₃ is a C₁-C₁₆ alkyl group.

33. The kit of claim 27, wherein R₃ is a C₁-C₁₀ alkyl group.

34. The kit of claim 27, wherein R₃ is a C₂-C₄ alkyl group.

35. The kit of claim 27, wherein R₃ is butyl.

36. The kit of claim 27, wherein said at least one monomer is butyl lactoyl cyanoacrylate.

37. The kit of claim 27, wherein said at least one monomer is butyl glycoloyl cyanoacrylate.

38. The kit of claim 27, wherein said polymerization initiator or accelerator has the following formula

wherein R₄, R₅, R₆ and R₇ are each independently H or a substituted or unsubstituted straight, branched or cyclic alkyl group;

a substituted or unsubstituted aromatic group;

a substituted or unsubstituted aralkyl group;

or a substituted or unsubstituted alkyl or aromatic group containing one or more hetero atoms; and

X⁻

is an anion.

39. The kit of claim 38, wherein at least one of R₄, R₅, R₆ and R₇ comprises at least one member selected from the group consisting of an aromatic ring and a hetero atom-containing linkage.

40. The kit of claim 38, wherein X⁻

is a halogen radical.

41. The kit of claim 27, wherein said polymerization initiator or accelerator is at least one member selected from the group consisting of domiphen bromide, butyrylcholine chloride, benzalkonium bromide, and acetyl choline chloride.

42. The kit of claim 27, wherein said adhesive composition further comprises at least one component selected from the group consisting of a thickener, a plasticizer, a colorant, a preservative, a heat dissipating agent, an acidic stabilizing agent, and a formaldehyde scavenger.

43. The kit of claim 38, wherein said adhesive composition further comprises at least one component selected from the group consisting of a thickener, a plasticizer, a colorant, a preservative, a heat dissipating agent, an acidic stabilizing agent, and a formaldehyde scavenger.

44. The kit of claim 27, wherein said adhesive composition further comprises at least one other cyanoacrylate monomer.

45. The kit of claim 27, wherein said adhesive composition has a Sterility Assurance Level (SAL) value of 10⁻

3-10<sup>−

6</sup>.

46. The kit of claim 27, wherein said kit has a Sterility Assurance Level (SAL) value of 10⁻

3-10<sup>−

6</sup>.

47. A method of treating living tissue, comprising:

applying to internal living tissue in a living organism a biocompatible adhesive composition comprising a polymerization initiator or accelerator and at least one monomer selected from the group consisting of butyl lactoyl cyanoacrylate monomer and butyl glycoloyl cyanoacrylate monomer.

48. The method of claim 47, wherein said polymerization initiator or accelerator is a quaternary amine.

49. The method of claim 47, wherein the polymerization initiator or accelerator is combined with said at least one monomer prior to applying the composition to said tissue.

50. The method of claim 47, wherein the polymerization initiator or accelerator is combined with said at least one monomer after said at least one monomer is applied to said tissue.

51. The method of claim 47, wherein said at least one monomer is added to the polymerization initiator or accelerator after the polymerization initiator or accelerator is applied to said tissue.

52. The method of claim 47, wherein said polymerization initiator or accelerator promotes polymerization of said at least one monomer at a rate suitable for medical application and produces a polymer that is absorbed by said living organism in less than 2 years.

53. The method of claim 47, wherein said polymerization initiator or accelerator has the following formula

wherein R₄, R₅, R₆ and R₇ are each independently H or a substituted or unsubstituted straight, branched or cyclic alkyl group; a substituted or unsubstituted aromatic group;

a substituted or unsubstituted aralkyl group;

or a substituted or unsubstituted alkyl or aromatic group containing one or more hetero atoms; and

X⁻

is an anion.

54. The method of claim 53, wherein at least one of R₄, R₅, R₆ and R₇ comprises at least one member selected from the group consisting of an aromatic ring and a hetero atom-containing linkage.

55. The method of claim 53, wherein X⁻

is a halogen radical.

56. The method of claim 47, wherein said polymerization initiator or accelerator is at least one member selected from the group consisting of domiphen bromide, butyrylcholine chloride, benzalkonium bromide, and acetyl choline chloride.

57. The method of claim 47, wherein said adhesive composition further comprises at least one component selected from the group consisting of a thickener, a plasticizer, a colorant, a preservative, a heat dissipating agent, an acidic stabilizing agent, and a formaldehyde scavenger.

58. A method of treating living tissue, comprising:

selecting an alkyl ester cyanoacrylate monomer for treatment of said tissue;

determining a desired rate at which an adhesive polymer of said monomer is absorbed;

selecting a suitable polymerization initiator or accelerator for said monomer on the basis of said desired rate; and

applying to living tissue said polymerization initiator or accelerator and said monomer to form an absorbable adhesive polymer on said tissue,

wherein said alkyl ester cyanoacrylate monomer has the formula

wherein R₁ and R₂ are independently H, a straight, branched or cyclic alkyl group, or are combined together in a cyclic alkyl group, and R₃ is a straight, branched or cyclic alkyl group.

59. The method of claim 58, wherein said alkyl ester cyanoacrylate monomer is at least one member selected from the group consisting of butyl lactoyl cyanoacrylate monomer and butyl glycoloyl cyanoacrylate monomer.

60. The method of claim 58, wherein said polymerization initiator or accelerator is a quaternary amine.

61. The method of claim 58, wherein said polymerization initiator or accelerator has the following formula

wherein R₄, R₅, R₆ and R₇ are each independently H or a substituted or unsubstituted straight, branched or cyclic alkyl group; a substituted or unsubstituted aromatic group;

a substituted or unsubstituted aralkyl group;

or a substituted or unsubstituted alkyl or aromatic group containing one or more hereto atoms; and

X⁻

is an anion.

62. The method of claim 61, wherein at least one of R₄, R₅, R₆ and R₇ comprises at least one member selected from the group consisting of an aromatic ring and a hetero atom-containing linkage.

63. The method of claim 58, wherein said polymerization initiator or accelerator is at least one member selected from the group consisting of domiphen bromide, butyrylcholine chloride, benzalkonium bromide, and acetyl choline chloride.

64. A biocompatible adhesive composition, comprising:

at least one alkyl ester cyanoacrylate monomer; and

a polymerization initiator or accelerator, wherein said polymerization initiator or accelerator is a quaternary amine,

wherein said at least one alkyl ester cyanoacrylate monomer has the formula

wherein R₁ and R₂ are independently H, a straight, branched or cyclic alkyl group, or are combined together in a cyclic alkyl group, and R₃ is a straight, branched or cyclic alkyl group.

65. The composition of claim 64, wherein said at least one monomer is butyl lactoyl cyanoacrylate.

66. The composition of claim 64, wherein said at least one monomer is butyl glycoloyl cyanoacrylate.

67. The composition of claim 64, wherein said polymerization initiator or accelerator has the formula

wherein R₄, R₅, R₆ and R₇ are each independently H or a substituted or unsubstituted straight, branched or cyclic alkyl group; a substituted or unsubstituted aromatic group;

a substituted or unsubstituted aralkyl group;

or a substituted or unsubstituted alkyl or aromatic group containing one or more hetero atoms; and

X⁻

is an anion.

68. The composition of claim 67, wherein at least one of R₄, R₅, P₆ and R₇ comprises at least one member selected from the group consisting of an aromatic ring and a hetero atom-containing linkage.

69. The composition of claim 64, wherein said polymerization initiator or accelerator is at least one member selected from the group consisting of domiphen bromide, butyrylcholine chloride, benzalkonium bromide, and acetyl choline chloride.

70. A polymerized film formed by curing the composition of claim 64.