Thrombin solution and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9212357-B2
Application number	US-201313783592-A
Country	US
Kind code	B2
Filing date	Mar 4, 2013
Priority date	Dec 3, 2012
Publication date	Dec 15, 2015
Grant date	Dec 15, 2015

Abstract

Provided are methods for lyophilization of an aqueous thrombin solution, thrombin solutions for use in such lyophilization methods, and solid thrombin compositions produced by such methods.

First claim

What is claimed is:

1. A method for lyophilization of an aqueous thrombin solution comprising about 1 to less than about 4.6% w/v of a saccharide or sugar alcohol; at least about 0.7 to lower than about 1.75% sodium chloride; about 0.2 to about 3% albumin; calcium chloride; and sodium acetate; wherein the solution is devoid of polyethylene glycol, the method comprising:
lyophilizing the aqueous thrombin solution, wherein the height of the aqueous thrombin solution in a lyophilization vessel is in the range of 6 mm to 10 mm, and wherein a total lyophilization time is no greater than about 35 hours.

2. The method of claim 1 , wherein the aqueous thrombin solution comprises about 200 to about 2000 IU/ml thrombin; about 0.3 to about 1.5% w/v calcium chloride; and about 0.14 to about 1% w/v sodium acetate.

3. The method of claim 2 , wherein the aqueous thrombin solution comprises: about 1.6 to less than about 4.6% w/v saccharide or sugar alcohol; about 0.7 to about 1.7% w/v sodium chloride; higher than about 0.2 to lower than about 3% albumin w/v; about 0.3 to about 1.2% w/v calcium chloride; and about 0.14 to about 0.7% w/v sodium acetate.

4. The method of claim 3 , wherein the saccharide or sugar alcohol is present at a concentration of 2% w/v; the albumin is present at a concentration of about 0.6% w/v; the sodium chloride is present at a concentration of about 0.76% w/v; the calcium chloride is present at a concentration of about 0.6% w/v and the sodium acetate is present at a concentration of about 0.27% w/v.

5. The method of claim 1 , the aqueous thrombin solution consisting essentially of thrombin; saccharide or sugar alcohol; sodium chloride; albumin; calcium chloride; and sodium acetate.

6. The method of claim 1 , wherein the sugar alcohol is mannitol.

7. The method of claim 6 , wherein the mannitol is present at a concentration of about 2% w/v.

8. The method of claim 1 , wherein the aqueous thrombin solution comprises a single saccharide or sugar alcohol.

9. The method of claim 1 , wherein the aqueous thrombin solution is devoid of histidine.

Assignees

• Omrix Biopharmaceuticals Ltd

Inventors

• Meidler Roberto
• Belyaev Oleg
• Bar Liliana
• Nur Israel

Classifications

• C12N9/6429

  Thrombin (3.4.21.5) · CPC title

• C12Y304/21005

  Thrombin (3.4.21.5) · CPC title

• C12N9/96 Primary

  Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates · CPC title

• A61K47/42

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• A61K38/4833

  Thrombin (3.4.21.5) · CPC title