Cellulose oxidation by nitrogen dioxide in a perfluorinated tertiary amine solvent

• US 20070054880A1
• Filed: 08/05/2004
• Published: 03/08/2007
• Est. Priority Date: 08/05/2004
• Status: Active Grant

• Current Assignee: Depuy Synthes Products Incorporated (Johnson & Johnson)
• Original Assignee: Xylos Corporation
• Inventors: Serafica, Gonzalo, Saferstein, Lowell
• Granted Patent: US 7,645,874 B2
• Time in Patent Office: Days
• US Class Current: 514/57
• CPC Class Codes: A61L 15/28 Polysaccharides or their derivatives A61L15/225 takes precedence
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: C08B 15/04 Carboxycellulose, e.g. prepared by oxidation with nitrogen dioxide
• CPC Class Codes: C08L 1/04 Oxycellulose; Hydrocellulose , e.g. microcrystalline cellulose

Abstract

This invention relates to a process for preparing bioabsorbable oxidized cellulose comprising combining cellulose material, with nitrogen dioxide and a nonaqueous solvent chosen from the class of perfluorinated tertiary amines. This invention also relates to a method of oxidizing cellulose material comprising introducing a solvent into the vessel, circulating the solvent through the cellulose material, adding nitrogen dioxide to said vessel containing the solvent and cellulose in the required amounts, circulating the solution for 7 to 24 hours while controlling the reaction temperature, and isolating the oxidized material. Preferably, isolation of the oxidized product is followed by first washing the oxidized cellulose material with cold water, then washing the oxidized cellulose material with an aqueous alcohol solution several times, then washing the material with 100% alcohol several times, and finally drying the oxidized material.

Claims

1. A method of making bioabsorbable oxidized cellulose comprising combining cellulose, nitrogen dioxide and a non-aqueous solvent selected from the group consisting of perfluorinated tertiary amines.

2. A method of making the bioabsorbable oxidized cellulose of claim 1 comprising:

a. introducing a cellulose material into a reaction vessel;

b. introducing a solvent into the reaction vessel of step (a);

c. circulating the solvent through the cellulose material;

d. adding the required amount of nitrogen dioxide to the reaction vessel containing the solvent and the cellulose material to make a solution;

e. circulating the solution for a period of time while controlling the reaction temperature; and

f. isolating the cellulose material after the desired degree of oxidation has been achieved.

3. The method of claim 2 wherein the solvent is selected from a group of perfluorinated tertiary amines with the formula N(C_xF_2x+1)₃, wherein x is a whole number from 1 to 10.

4. The method of claim 3 wherein x is 3.

5. The method of claim 2 wherein the cellulose is microbial cellulose.

6. The method of claim 5 wherein the microbial cellulose is produced by Acetobacter xylinum.

7. The method of claim 2 wherein the cellulose material is selected from the group consisting of powders, sponges, knitted fabrics, woven fabrics, and non-woven fabrics.

8. The method of claim 7 wherein the non-woven fabric is selected from the group consisting of cotton, rayon, lyocell fibers, or other cellulosic or polysaccharide based fibers.

9. The method of claim 7 wherein the cellulose material is selected from the group consisting of cellulose films, cellulose paper, cotton balls, rayon balls, cotton fibers, rayon fibers, lyocell fibers, or a cellulose pellicle produced by Acetobacter xylinum.

10. The method of claim 2 wherein the desired degree of oxidation achieved by varying a factor selected from the group consisting of nitrogen concentration, reaction temperature, reaction duration, or a combination of these factors.

11. The method of claim 2 wherein the appropriate amount of nitrogen dioxide ranges from 5% to 15%.

12. The method of claim 2 wherein the appropriate amount of nitrogen dioxide is a ratio of nitrogen dioxide to cellulose that ranges from 0.5 to 5.

13. The method of claim 12 wherein the ratio ranges from 0.8 to 3.

14. The method of claim 2 wherein the amount of nitrogen dioxide in the solution is varied throughout the duration of the reaction.

15. The method of claim 2 wherein the temperature is between −

20°

C. and 60°

C.

16. The method of claim 2 wherein the temperature is between 25°

C. and 50°

C.

17. The method of claim 2 wherein the temperature is constant throughout the oxidation process.

18. The method of claim 2 wherein the temperature is adjusted during the oxidation process.

19. The method of claim 2 wherein the solution is circulated for 6 hours to 24 hours.

20. The method of claim 21 wherein the solution is circulated for 8 hours to 12 hours.

21. The method of claim 2 wherein the degree of oxidation is achieved by varying the duration of the reaction.

22. The method of claim 2 wherein the vessel is a pressure vessel.

23. The method of claim 2 wherein the vessel is a vessel vented to the atmosphere.

24. The method of claim 2 wherein the oxidized material is isolated comprising:

a. removing the oxidized cellulose material;

b. placing the material in an aqueous solution;

c. removing the material from the aqueous solution;

d. performing a first washing of the oxidized cellulose material;

e. performing a second washing of the oxidized cellulose material;

f. performing a third washing of the oxidized cellulose material; and

g. drying the oxidized cellulose material.

25. The method of claim 24 wherein the aqueous solution is dilute sodium hydroxide comprising a concentration of less that 0.5N NaOH.

26. The method of claim 24 wherein the first washing is performed using water that is below 20°

C.

27. The method of claim 24 wherein the second washing is performed using an aqueous alcohol solution comprising a percentage of alcohol equal to or greater than 50%.

28. The method of claim 27 wherein the alcohol is selected from the group consisting of isopropyl, ethyl, or methyl alcohol.

29. The method of claim 27 wherein the second washing is performed at least two times or at least until there is no visible sign of nitrogen tetroxide in the sample.

30. The method of claim 24 wherein the third washing is performed with 100% alcohol.

31. The method of claim 30 wherein the alcohol is selected from the group consisting of isopropyl, ethyl, or methyl alcohol.

32. The method of claim 30 wherein the third washing is performed until the residual water in the sample is less than 1%.

33. The method of claim 24 wherein the oxidized cellulose material is dried by a method selected from the group consisting of air-dried, oven dried, or supercritical fluid drying.

34. The method of claim 33 wherein the supercritical fluid is CO₂.

35. A bioabsorbable oxidized cellulose material for use as a medical material produced by the method of claim 1.

36. A bioabsorbable oxidized cellulose material for use as a medical material produced by the method of claim 2.

37. A bioabsorbable oxidized cellulose material for use as a medical material produced by the method of claim 24.

38. The bioabsorbable oxidized cellulose material of claim 35 wherein the medical material is selected from the group consisting of sutures, hemostats, wound coverings, implantable tissue substitutes, tissue engineering matrices, or adhesion prevention devices.

39. The bioabsorbable oxidized cellulose material of claim 36 wherein the medical material is selected from the group consisting of sutures, hemostats, wound coverings, implantable tissue substitutes, tissue engineering matrices, or adhesion prevention devices.

40. The bioabsorbable oxidized cellulose material of claim 37 wherein the medical material is selected from the group consisting of sutures, hemostats, wound coverings, implantable tissue substitutes, tissue engineering matrices, or adhesion prevention devices.