Sterile hyaluronic acid solutions

• US 8,283,463 B2
• Filed: 02/09/2010
• Issued: 10/09/2012
• Est. Priority Date: 02/09/2010
• Status: Active Grant

• Current Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Original Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Inventors: Liu, X. Michael, Heiler, David J., Menzel, Thomas, Brongo, Abbie, Burke, Susan E., Cummins, Karl
• Primary Examiner(s): OLSON, ERIC
• Application Number:
  US12/702,540
• Publication Number:
  US 20110195925A1
• Time in Patent Office: 973 Days
• Field of Search: None
• US Class Current: 536/55.2
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61L 2/022 Filtration
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions
• CPC Class Codes: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates

Abstract

A process for sterilizing a solution comprising hyaluronic acid. The process comprises providing an aqueous solution of hyaluronic acid with a weight average molecular weight from 0.6 MDa to 3.6 MDa, and the concentration of the hyaluronic acid is from 0.04% to 0.8% by weight. The aqueous solution also has an ionic strength equivalent to an aqueous concentration of sodium chloride from 3% to 30% by weight. Once the aqueous, high salt, hyaluronic acid solution is prepared the solution is maintained at a temperature from 40° C. to 80° C. for at least 1 hour and not longer than six days. Following the heat treatment step, the aqueous solution is filtered through a sterilization filter medium to provide a sterilized high salt, hyaluronic acid solution.

Claims

1. A process for sterilizing a solution, the process comprising:

providing an aqueous solution of hyaluronic acid having a weight average molecular weight from 0.6 MDa to 3.6 MDa, and the concentration of the hyaluronic acid is from 0.04% to 0.8% by weight;

wherein the aqueous solution has an ionic strength equivalent to an aqueous concentration of sodium chloride from 3% to 30% by weight to provide a high salt, hyaluronic acid solution;

maintaining the aqueous high salt, hyaluronic acid solution at a temperature from 40°

C. to 80°

C. for at least 1 hour and not longer than six days; and

filtering the heated, high salt, hyaluronic acid solution through a sterilization filter medium, wherein the filter medium has an average pore size of 0.25 μ

m or less to provide a sterilized high salt, hyaluronic acid solution.

2. The process of claim 1 wherein the hyaluronic acid has a weight average molecular weight from 0.8 MDa to 2.2 MDa.

3. The process of claim 1 wherein the concentration of the hyaluronic acid is from 0.1% to 0.5% by weight.

4. The process of claim 1 wherein providing the high salt, hyaluronic acid solution comprises combining and mixing an appropriate dry weight of salt and hyaluronic acid to from a dry blend of the salt and hyaluronic acid, and adding the dry blend to an appropriate amount of purified water.

5. The process of claim 4 wherein the purified water is pre-heated to a temperature from 40°

C. to 70°

C.

6. The process of claim 1 wherein the maintaining of the aqueous high salt, hyaluronic acid solution aqueous high salt comprises maintaining at a temperature from 50°

C. to 65°

C. for at least 1 hour and not longer that 12 hours.

7. The process of claim 1 further comprising combining the sterilized high salt, hyaluronic acid solution with an aqueous solution comprising buffer components and adjusting the pH from 6.4 to 7.2, and by the combining of the two aqueous solutions the sterilized high salt, hyaluronic acid solution is diluted by a factor of at least 10.

8. The process of claim 1 wherein the sterilized high salt, hyaluronic acid solution has a pH of 6.4 to 7.2.

9. The process of claim 7 wherein the buffer components comprise boric acid and sodium borate.

10. The process of claim 1 wherein the sterilized high salt, hyaluronic acid solution has a concentration of the hyaluronic acid from 0.15% to 0.6% by weight, and additionally contains sodium chloride at a concentration of from 4% to 16% by weight.

11. The process of claim 1 wherein the sterilization filter medium is a polyvinylidene fluoride filter cartridge.

12. A process for sterilizing a solution comprising hyaluronic acid, the process comprising:

providing an aqueous solution of hyaluronic acid with a weight average molecular weight from 0.6 MDa to 2.2 MDa, and the concentration of the hyaluronic acid is from 0.08% to 0.5% by weight;

wherein the aqueous solution has an ionic strength equivalent to an aqueous concentration of sodium chloride from 4% to 18% by weight to provide a high salt, hyaluronic acid solution;

maintaining the aqueous high salt, hyaluronic acid solution at a temperature from 50°

C. to 75°

C. for at least 1 hour and not longer than 18 hours; and

filtering the heated, high salt, hyaluronic acid solution through a sterilization filter medium, wherein the filter medium has an average pore size of 0.25 μ

m or less to provide a sterilized high salt, hyaluronic acid solution.

13. The process of claim 12 wherein tile sterilized high salt, hyaluronic acid solution has a concentration of the hyaluronic acid from 0.1% to 0.4% by weight, and additionally contains sodium chloride at a concentration of from 8% to 16% by weight.

14. The process of claim 12 wherein providing the high salt, hyaluronic acid solution comprises combining and mixing an appropriate dry weight of salt and hyaluronic acid to from a dry blend of the salt and hyaluronic acid, and adding the dry blend to an appropriate amount of purified water.

15. The process of claim 12 further comprising combining the sterilized high salt, hyaluronic acid solution with an aqueous solution comprising buffer components selected from the group consisting of boric acid, sodium borate, sodium dihydrogen phosphate and adjusting the pH from 6.4 to 7.2, and by the combining of the two aqueous solutions the sterilized high salt, hyaluronic acid solution is diluted by a factor of at least 5.

16. The process of claim 15 wherein the combined aqueous solutions further comprise stabilized chlorine in a preservative effective amount.

17. The process of claim 12 wherein the sterilization filter medium is a polyvinylidene fluoride filter cartridge.

18. A process of preparing a production batch of a contact lens care solution, the process comprising:

providing an aqueous solution of hyaluronic acid with a weight average molecular weight from 0.6 MDa to 3.6 MDa, and the concentration of the hyaluronic acid is from 0.04% to 0.8% by weight;

wherein the aqueous solution has an ionic strength equivalent to an aqueous concentration of sodium chloride from 2% to 30% by weight to provide a high salt, hyaluronic acid solution;

maintaining the aqueous high salt, hyaluronic acid solution at a temperature from 55°

C. to 75°

C. for at least 1 hour and not longer than 12 hours;

filtering the heated, high salt, hyaluronic acid solution through a sterilization filter medium, wherein the filter medium has an average pore size of 0.25 μ

m or less to provide a sterilized high salt, hyaluronic acid solution;

combining the sterilized high salt, hyaluronic acid solution with an aqueous solution comprising buffer components and adjusting the pH from 6.4 to 7.2, and by the combining of the two aqueous solutions the sterilized high salt, hyaluronic acid solution is diluted by a factor of at least 10.

19. The process of claim 18 wherein the combined aqueous solutions further comprise poly(hexamethylene biguanide), which is present from 0.5 ppm to 2.0 ppm.

20. The process of claim 19 wherein the combined aqueous solutions further comprise α

-[4-tris(2-hydroxyethyl)-ammonium chloride-2-butenyl]poly[1-dimethyl ammonium chloride-2-butenyl]-ω

-tris(2-hydroxyethyl)ammonium chloride, which is present from 0.5 ppm to 3 ppm.

21. The process of claim 18 wherein the production batch has a final total solution volume from 5,000 L to 40,000 L.