Process for sterilization of and cyanoacrylate adhesives compositions and devices

• US 20060062687A1
• Filed: 09/17/2004
• Published: 03/23/2006
• Est. Priority Date: 09/17/2004
• Status: Active Grant

• Current Assignee: Clast Trading Ltd.
• Original Assignee: Clast Trading Ltd.
• Inventors: Morales, Carlos R.
• Granted Patent: US 8,110,144 B2
• Time in Patent Office: Days
• US Class Current: 422/1
• CPC Class Codes: A61L 2/04 Heat A61L2/08 takes precedence
• CPC Class Codes: A61L 2/28 Devices for testing the effectiveness or completeness of sterilisation, e.g. indicators which change colour apparatus involving enzymes or microorganisms C12M1/34; methods involving enzymes or microorganisms C12Q1/00
• CPC Class Codes: C09J 4/06 Organic non-macromolecular compounds having at least one polymerisable carbon-to-carbon unsaturated bond in combination with a macromolecular compound other than an unsaturated polymer of groups C09J159/00 - C09J187/00
• CPC Class Codes: C12Q 1/22 Testing for sterility conditions
• CPC Class Codes: Y10T 428/13 Hollow or container type article [e.g., tube, vase, etc.]
• CPC Class Codes: Y10T 428/131 Glass, ceramic, or sintered, fused, fired, or calcined metal oxide or metal carbide containing [e.g., porcelain, brick, cement, etc.]
• CPC Class Codes: Y10T 428/1352 Polymer or resin containing [i.e., natural or synthetic]

Abstract

Discosed are a process for sterilization of cyanoacrylate adhesive compositions, the compositions, comprising 2-cyanoacrylate ester monomers, so produced and a method for assaying the effectiveness of the sterilization process. The process comprises heating the adhesive composition to from about 70° C. to about 140° C. for an effective amount of time. The effectiveness of the process can be assayed by disposing bacterial spores in the cyanoacrylate monomer, exposing the composition to a dry heat sterilization process, transferring the cyanoacrylate composition to a sterile aldose solution, transferring and exposing the sample to a nutrient medium which supports germination and growth of viable spores, incubating the samples, and determining the presence or absence of growth.

Claims

1. A method of sterilization of 2-cyanoacrylate adhesive compositions, comprising;

heating said composition in a device at a temperature of from about 70°

C. to about 140°

C. for a period of time sufficient to sterilize the composition.

2. A method according to claim 1 wherein said sterilization temperature is from about 70°

C. to about 110°

C.

3. A method according to claim 1 wherein said sterilization temperature is from about 70°

C. to about 100°

C.

4. A method as in any one of claims 1, 2 and 3 wherein said cyanoacrylate composition comprises one or more 2-cyanoacrylate ester monomers wherein said cyanoacrylate ester monomer is an alkyl, cycloalkyl, fluoroalkyl, fluorocycloalkyl or fluoroalkoxy 2-cyanoacrylate monomer.

5. A method according to claim 3 wherein said cyanoacrylate composition further comprises at least one thickener selected from the group consisting of poly alkyl-2-cyanoacrylates, poly cycloalkyl-2-cyanoacrylates, poly fluoroalkyl-2-cyanoacrylates, poly fluorocycloalkyl-2-cyanoacrylates, poly alkoxyalkyl-2-cyanoacrylates, poly alkoxycycloalkyl-2-cyanoacrylates, poly fluoroalkoxyalkyl-2-cyanoacrylates, polyalkoxycyclofluoroalkyl-2-cyanoacrylates, poly lactic acid and poly gylcolic acid.

6. A method according to claim 5 wherein the at least one thickener is a poly alkyl-2-cyanoacrylate.

7. A method according to claim 6 wherein the alkyl group of the poly alkyl-2-cyanoacrylate is selected from the group consisting of straight chain or branched chain C₄ to C₈ hydrocarbons.

8. A method according to claim 6 wherein said thickening polymer is poly octyl 2-cyanoacrylate.

9. A method according to claim 5 wherein the 2-cyanoacrylate composition further comprises a stabilizer.

10. A method according to claim 9 wherein said stabilizer is one or more of an anionic polymerization inhibitor or a free radical polymerization inhibitor.

11. A method according to claim 5 wherein said cyanoacrylate composition further comprises a plasticizer selected from the group consisting of tributyl acetyl citrate, dimethyl sebacate, diethyl sebacate, triethyl phosphate, tri-(2-ethylhexyl) phosphate, tricresyl phosphate, glycerol triacetate, glycerol tributyrate, dioctyl adipate, isopropyl myristate, butyl stearate, trioctyl trimellitate and dioctyl glutarate.

12. A method according to claim 11 wherein said plasticizer is up to 50% by weight of the cyanoacrylate composition.

13. A composition comprising a sterile 2-cyanoacrylate ester composition for use in medicine, or surgery, said composition disposed in a sealed aluminum container, said preparation sterilized by heating the composition to a temperature of from about 70°

C. to about 140°

C. for a period of time sufficient to sterilize said preparation.

14. A composition according to claim 13 wherein the sterilization temperature is from about 70°

C. to about 100°

C.

15. A composition as in any one of claims 13 and 14 wherein said cyanoacrylate composition comprises one or more 2-cyanoacrylate ester monomers wherein said cyanoacrylate ester monomer is an alkyl, cycloalkyl, fluoroalkyl, fluorocycloalkyl or fluoroalkoxy 2-cyanoacrylate monomer.

16. A composition according to claim 14 further comprising at least one thickener selected from the group consisting of poly alkyl-2-cyanoacrylates, poly cycloalkyl-2-cyanoacrylates, poly fluoroalkyl-2-cyanoacrylates, poly fluorocycloalkyl-2-cyanoacrylates, poly alkoxyalkyl-2-cyanoacrylates, poly alkoxycycloalkyl-2-cyanoacrylates, poly fluoroalkoxyalkyl-2-cyanoacrylates, polyalkoxycyclofluoroalkyl-2-cyanoacrylates, poly lactic acid and poly gylcolic acid.

17. A composition according to claim 16 wherein the thickener is a poly alkyl-2-cyanoacrylate.

18. A composition according to claim 17 wherein the alkyl group of the poly alkyl-2-cyanoacrylate is selected from the group consisting of straight chain or branched chain C₄ to C₈ hydrocarbons.

19. A composition according to claim 17 wherein the thickener is poly octyl-2-cyanoacrylate.

20. A composition according to claim 13 wherein the 2-cyanoacrylate composition further comprises a stabilizer.

21. A composition according to claim 20 wherein said stabilizer is one or more of an anionic polymerization inhibitor or a free radical polymerization inhibitor.

22. A composition according to claim 13 wherein said cyanoacrylate composition further comprises a plasticizer selected from the group consisting of tributyl acetyl citrate, dimethyl sebacate, diethyl sebacate, triethyl phosphate, tri-(2-ethylhexyl) phosphate, tricresyl phosphate, glycerol triacetate, glycerol tributyrate, dioctyl adipate, isopropyl myristate, butyl stearate, trioctyl trimellitate and dioctyl glutarate.

23. A composition according to claim 22 wherein said plasticizer is up to 50% by weight of the cyanoacrylate composition.

24. A sterile adhesive composition, comprising;

at least one 2-cyanoacrylate monomer and

at least one thickener wherein said thickener is selected from the group consisting of poly alkyl-2-cyanoacrylates, poly cycloalkyl-2-cyanoacrylates, poly fluoroalkyl-2-cyanoacrylates, poly fluorocycloalkyl-2-cyanoacrylates, poly alkoxyalkyl-2-cyanoacrylates, poly alkoxycycloalkyl-2-cyanoacrylates, poly fluoroalkoxyalkyl-2-cyanoacrylates, polyalkoxycylcylofluoroalkyl-2-cyanoacrylates, poly lactic acid and poly gylcolic acid.

25. An adhesive composition according to claim 24 wherein said thickener is a polyalkyl-2-cyanoacrylate.

26. An adhesive composition according to claim 25 wherein the alkyl group of the poly alkyl-2-cyanoacrylate is selected from the group consisting of straight chain or branched chain C₄ to C₈ hydrocarbons.

27. An adhesive composition according to claim 25 wherein said thickener is polyoctyl-2-cyanoacrylate.

28. An adhesive composition according to claim 24 wherein said thickener is present in from about 1% to about 25% by weight of the composition.

29. An adhesive composition according to claim 24 wherein said thickener is present in from about 1% to about 10% by weight of the composition.

30. An adhesive composition according to claim 24 wherein said thickener is present in from about 1% to about 5% by weight of the composition.

31. A method for determining the effectiveness of a sterilization process comprising the steps of;

disposing bacterial spores as a biological indicator in a cyanoacrylate composition;

exposing the composition to a dry heat sterilization process along with the samples to be sterilized;

transferring the cyanoacrylate composition to a sterile aldose solution;

transferring and exposing the test sample to a quantity of a nutrient medium which supports germination and growth of any remaining viable spores;

incubating the remaining spores and nutrient medium for a period of time to promote the germination and growth of any viable microorganisms;

and for the presence or absence of growth of the sample to determine the effectiveness of the sterilization.

32. A method as in claim 31 wherein the cyanoacrylate composition was inoculated with lyophilized spores wherein the spores were selected from the group consisting of Bacillus subtillis and Geobacillus stearothermophillus.[DL1]

33. A method as in claim 31 wherein bacterial spores were disposed in the cyanoacrylate composition on any one of a group selected from bacterial spores on a stainless steel disc, bacterial spores on a steel wire, bacterial spores on steel coupons, bacterial spores on borosilicate paper and bacterial spores on woven cotton threads.

34. A method as in claim 31 wherein the aldose solution is selected from the group consisting of aqueous solutions of dextrose, lactose, arabinose, mannose, galactose, rhamnose, fructose, sucrose, and glucose.

35. A method as in claim 34 wherein the aldose is dextrose.

36. A method as in claim 35 wherein the concentration of the dextrose solution is from 2 to 20% by weight.

37. A method as in claim 36 wherein the concentration of the dextrose solution is from about 3% to about 15% by weight.

38. A method as in claim 37 wherein the concentration of the dextrose solution is from about 5% to about 10% by weight.

39. A method as in claim 31 wherein the nutrient medium is Soy-casein digested broth.

40. A method as in claim 31 wherein the samples were incubated at from about 28°

C. to about 37°

C.

41. A method as in claim 31 wherein the samples were incubated for at least 7 days.

42. A method as in claim 31 wherein bacterial germination and growth was detected by performing a gram stain smear examination of the incubated mixture of cyanoacrylate-sterile dextrose solution.

43. A method as in claim 31 wherein bacterial germination and growth was detected by addition of a Tetrazolium salt indicator followed by UV spectrophotometric analysis.

44. A method as in claim 31 wherein bacterial germination and growth was detected by direct UV spectrophotometric analysis.