Method for sterilization of aqueous polysaccharide solutions and sterile aqueous polysaccharide solutions

Patent metadata

Field	Value
Publication number	US-10307496-B2
Application number	US-201615375666-A
Country	US
Kind code	B2
Filing date	Dec 12, 2016
Priority date	Dec 22, 2015
Publication date	Jun 4, 2019
Grant date	Jun 4, 2019

Abstract

Sterilization method according to which an aqueous polysaccharide solution is stored in the presence of a lactone and a buffer system for a period of at least 24 hours, and a sterile polysaccharide solution produced in this way.

First claim

The invention claimed is:

1. Method for sterilizing aqueous polysaccharide solutions, comprising:
adding a β-lactone to an aqueous solution of a polysaccharide in the presence of a buffer, thereby forming a mixture; and
storing the mixture at a temperature of 4° C. to 40° C. for a period of at least 24 hours, wherein the added β-lactone is present in the mixture in an amount greater than or equal to 0.5% by weight.

2. Method according to claim 1 , wherein the β-lactone is selected from compounds (a1) that are represented by general formula (I),

where R1, R2, R3, and R4, independently of each other, represent H, a substituted or non-substituted alkyl residue, halogen residue, nitro residue or cyano residue, and compounds (a2) that are selected from the group consisting of dimers of compounds (a1).

3. Method according to claim 2 , wherein the β-lactone is β-propiolactone (CAS number 57-57-8).

4. Method according to claim 1 , wherein the polysaccharide is selected from the group consisting of the sodium salt of hyaluronic acid, the sodium salt of carboxymethylcellulose, hydroxyethylcellulose, hydroxyethyl starch, methylcellulose, and oxidized cellulose.

5. Method according to claim 1 , wherein phosphate buffer with a pH value of 7.0-8.0 is used as buffer system.

6. Method according to claim 5 , wherein the phosphate buffer is selected from the group consisting of the combination of potassium hydrogenphosphate and disodium hydrogenphosphate, the combination of sodium hydrogenphosphate and disodium hydrogenphosphate, the combination of disodium phosphate and phosphoric acid, the combination of trisodium phosphate and sodium hydrogenphosphate, and the combination of trisodium phosphate and phosphoric acid.

7. Method according to claim 4 , wherein the 3-hydroxypropionic acid produced by the hydrolysis of the β-propiolactone is a component of the buffer system.

8. Method according to claim 7 , wherein the 3-hydroxypropanoic acid and the sodium salt of the hyaluronic acid or 3-hydroxypropanoic acid and the sodium salt of the carboxymethylcellulose form a buffer system.

9. Method according to claim 1 , wherein all of the components of the buffer together are dissolved in the aqueous polysaccharide solution at a concentration of greater than or equal to 0.5% by weight.

10. Method according to claim 1 , wherein the sterilization of the aqueous polysaccharide solution takes place inside a primary packaging means.

11. Method according to claim 10 , wherein the aqueous polysaccharide solution and the β-lactone are mixed immediately before the aqueous polysaccharide solution is filled into the primary packaging means.

12. Method according to claim 1 , wherein
the aqueous solution comprises a buffer system whose buffering capacity is sufficient to buffer the 3-hydroxypropanoic acid generated by hydrolysis of the β-lactone such that the pH value of the sterilized aqueous polysaccharide solution is equal to that of the unsterilized polysaccharide solution.

13. Sterile polysaccharide solution produced according to the method of claim 1 , wherein the aqueous polysaccharide solution comprises at least one polysaccharide that is at least partially soluble in water, in water and 3-hydroxypropionic acid, and in a buffer system.

14. Sterile polysaccharide solution according to claim 13 , wherein the buffer system comprises sodium ions, dihydrogenphosphate ions, hydrogenphosphate ions, phosphate ions, 3-hydroxypropionic acid, and 3-hydroxypropionate.

15. A visco-supplementation or a pharmaceutical drug carrier in human and veterinary medicine, comprising a sterile polysaccharide solution produced with the method according to claim 1 .

Assignees

• Heraeus Medical Gmbh

Inventors

• Vogt Sebastian
• Kluge Thomas

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P41/00

  Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• A61L2/16 Primary

  using chemical substances · CPC title

• A61L2103/05

  Living organisms or biological materials · CPC title