X-ray sterilization of liquid adhesive compositions
The invention provides a method of preparing a sterile, liquid adhesive composition in a sealed container using X-ray irradiation. The liquid adhesive compositions maintain their stability after sterilization and have an extended shelf life, making them particularly useful in the medical field.
1. A method for preparing a sterile, liquid monomeric cyanoacrylate adhesive composition in a sealed container using X-ray radiation, wherein the method comprises:
(a) stabilizing a liquid monomeric cyanoacrylate adhesive composition using a combination of a free radical stabilizer and an anionic stabilizer to produce a stabilized liquid monomeric cyanoacrylate adhesive composition;
(b) placing the stabilized liquid monomeric cyanoacrylate adhesive composition in a container and sealing said container; and
(c) irradiating the stabilized liquid monomeric cyanoacrylate adhesive composition in said sealed container with X-ray radiation at a dose of from about 5 kGy to about 40 kGy, thereby producing a sterilized, stabilized liquid monomeric cyanoacrylate adhesive composition, wherein the sterilized, stabilized liquid monomeric cyanoacrylate adhesive composition exhibits no change in viscosity or a negligible change in viscosity after irradiation, and has a shelf life of at least two years at ambient temperature.
2. The method of claim 1 wherein the dose of X-ray radiation is from about 5 kGy to about 30 kGy.
3. The method of claim 2 wherein the dose of X-ray radiation is from about 5 kGy to about 25 kGy.
4. The method of claim 3 wherein the dose of X-ray radiation is from about 5 kGy to about 20 kGy.
5. The method of claim 1 wherein the liquid monomeric cyanoacrylate adhesive composition comprises a crown ether.
6. The method of claim 1 wherein the liquid monomeric cyanoacrylate adhesive composition comprises an alpha-cyanoacrylate monomer.
7. The method of claim 6 wherein the alpha-cyanoacrylate monomer is selected from the group consisting of: 2-octyl cyanoacrylate, dodecyl cyanoacrylate, 2-ethylhexyl cyanoacrylate, n-butyl cyanoacrylate, methyl cyanoacrylate, 3-methoxybutyl cyanoacrylate, 2-butoxyethyl cyanoacrylate, 2-isopropoxyethyl cyanoacrylate, or 1-methoxy-2-propyl cyanoacrylate, and mixtures thereof.
8. The method of claim 7 wherein the alpha-cyanoacrylate monomer is selected from the group consisting of: n-butyl cyanoacrylate, 2-octyl cyanoacrylate, and a mixture thereof.
9. The method of claim 1 wherein the container comprises an inner-most layer comprising a nitrile polymer.
10. The method of claim 1 further comprising the step of filtering the liquid monomeric cyanoacrylate adhesive composition through at least one filter under an inert and moisture-free atmosphere prior to the irradiation step, wherein the at least one filter has a pore size of from about 1 to about 200 μm.
11. A method for preparing a sterile, liquid monomeric cyanoacrylate adhesive composition in a sealed container using X-ray radiation, wherein the method comprises:
(a) stabilizing a liquid monomeric cyanoacrylate adhesive composition with 2000 ppm to 8000 ppm of a free radical stabilizer selected from the group consisting of butylated hydroxy anisole (BHA), hydroquinone, catechol, hydroquinone monomethyl ether, butylated hydroxyanisol, 4-ethoxyphenol, 4-methoxyphenol, 3-methoxyphenol, 2-tert-butyl-4-methoxyphenol and 2,2-methylene-bis-(4-methyl-6-tert-butylphenol) and with either about 10 ppm to about 200 ppm of sulfur dioxide or about 5 ppm to about 50 ppm of a strong acid anionic stabilizer selected from the group consisting of perchloric acid, hydrochloric acid, hydrobromic acid, toluenesulfonic acid, fluorosulfonic acid, phosphoric acid, ortho-pohsphoric acid, meta-phosphoric acid, para-phosphoric acid, trichloroacetic acid, and sulfuric acid;
(b) placing the stabilized liquid monomeric cyanoacrylate adhesive composition in a container and sealing said container; and
(c) irradiating the stabilized liquid monomeric adhesive composition in said sealed container with X-ray radiation at a dose of from about 5 kGy to about 40 kGy, thereby producing a sterilized, stabilized liquid monomeric cyanoacrylate adhesive composition, wherein the sterilized, stabilized liquid monomeric cyanoacrylate adhesive composition exhibits no change in viscosity or a negligible change in viscosity after irradiation, and has a shelf life of at least two years at ambient temperature.
12. The method of claim 11 wherein the dose of X-ray radiation is from about 5 kGy to about 30 kGy.
13. The method of claim 12 wherein the dose of X-ray radiation is from about 5 kGy to about 25 kGy.
14. The method of claim 13 wherein the dose of X-ray radiation is from about 5 kGy to about 20 kGy.
15. The method of claim 11 wherein the liquid monomeric cyanoacrylate adhesive composition comprises an alpha-cyanoacrylate monomer.
16. The method of claim 15 wherein the alpha-cyanoacrylate monomer is selected from the group consisting of: 2-octyl cyanoacrylate, dodecyl cyanoacrylate, 2-ethylhexyl cyanoacrylate, n-butyl cyanoacrylate, methyl cyanoacrylate, 3-methoxybutyl cyanoacrylate, 2-butoxyethyl cyanoacrylate, 2-isopropoxyethyl cyanoacrylate, or 1-methoxy-2-propyl cyanoacrylate, and mixtures thereof.
17. The method of claim 16 wherein the alpha-cyanoacrylate monomer is selected from the group consisting of: n-butyl cyanoacrylate, 2-octyl cyanoacrylate, and a mixture thereof.
18. The method of claim 11 wherein the container comprises an inner-most layer comprising a nitrile polymer.
19. The method of claim 11 further comprising the step of filtering the liquid monomeric cyanoacrylate adhesive composition through at least one filter under an inert and moisture-free atmosphere prior to the irradiation step, wherein the at least one filter has a pore size of from about 1 to about 200 μm.
20. The method of claim 11 wherein the liquid monomeric cyanoacrylate adhesive composition comprises a crown ether.