Stable thermolysin hydrogel

Patent metadata

Field	Value
Publication number	US-11446364-B2
Application number	US-201314441135-A
Country	US
Kind code	B2
Filing date	Nov 14, 2013
Priority date	Nov 14, 2012
Publication date	Sep 20, 2022
Grant date	Sep 20, 2022

Abstract

Disclosed is a hydrogel comprising a hydrophilic gelling agent that includes a nonionic cellulose ether, and active thermolysin, wherein the proteolytic activity of the thermolysin does not decrease by more than 20% when stored at room temperature for 6 months.

First claim

The invention claimed is:

1. A hydrogel comprising:
(a) a hydrophilic gelling agent that includes a nonionic cellulose ether; and
(b) active thermolysin,
wherein the proteolytic activity of the thermolysin does not decrease by more than 20% when stored at room temperature for 6 months,
wherein the hydrogel further comprises a preservative and/or is sterile,
wherein the nonionic cellulose ether is hydroxyethylcellulose, hydroxypropylcellulose, or the combination thereof, and
wherein the hydrogel has a viscosity of 15,000 to 100,000 cps, as measured with a Brookfield RV Viscometer, spindle 14 with small sample adapter, at 10 rpm at room temperature read at 30 seconds.

2. The hydrogel of claim 1 , wherein the proteolytic activity of the thermolysin does not decrease by more than 10% when stored at room temperature for 6 months.

3. The hydrogel of claim 1 , wherein the proteolytic activity of the thermolysin does not decrease by more than 10% when stored at room temperature for 24 months.

4. The hydrogel of claim 1 , wherein the nonionic cellulose ether comprises hydroxyethylcellulose, and wherein the hydrogel comprises 2.5 to 4.5% w/w of the hydroxyethylcellulose.

5. The hydrogel of claim 1 , wherein the nonionic cellulose ether comprises hydroxypropylcellulose, and wherein the hydrogel comprises 0.01 to 10% w/w of the hydroxypropylcellulose.

6. The hydrogel of claim 1 , comprising 0.5 to 1% w/w/ of the thermolysin.

7. The hydrogel of claim 1 , comprising 0.1 to 5% w/w of the thermolysin.

8. The hydrogel of claim 1 , further comprising a buffer having a pH of 7.0 to 8.0.

9. The hydrogel of claim 8 , wherein the hydrogel comprises a buffer having a pH of about 7.5.

10. The hydrogel of claim 1 , wherein the hydrogel further comprises a metal salt.

11. The hydrogel of claim 10 , wherein the metal salt is sodium chloride or calcium chloride or mixtures thereof.

12. The hydrogel of claim 1 , wherein the preservative is methylparaben, propylparaben, or phenoxyethanol, or mixtures thereof.

13. The hydrogel of claim 1 , wherein the thermolysin is solubilized within the hydrogel.

14. The hydrogel of claim 1 , wherein the thermolysin is suspended within the hydrogel.

15. The hydrogel of claim 1 , wherein the thermolysin is partially solubilized and partially suspended within the hydrogel.

16. A method of debriding a wound comprising topically applying a composition according to claim 1 to a wound in need of debridement.

17. The method of claim 16 , wherein the wound is a chronic wound.

18. The method of claim 17 , wherein the chronic wound is a diabetic foot ulcer, a venous leg ulcer, an arterial leg ulcer, a decubitus ulcer, a stasis ulcer, a dermal ulcer, a burn, or a pressure ulcer.

19. The method of claim 16 , wherein the wound includes necrotic tissue.

20. The method of claim 19 , wherein the necrotic tissue is an eschar.

21. A method for stabilizing thermolysin comprising preparing a hydrogel according to claim 1 .

Assignees

• Smith & Nephew Inc

Inventors

• Shi Lei
• Jovanovic Aleksa
• Carson Dennis

Classifications

• A61L26/008

  Hydrogels or hydrocolloids · CPC title

• A61L26/0066

  Medicaments; Biocides · CPC title

• A61L2300/254

  Enzymes, proenzymes · CPC title

• C12Y304/24027

  Thermolysin (3.4.24.27) · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title