Stable biodegradable, high water absorbable polyglutamic acid hydrogel by 3-dimensional cross-linking and its preparation method
The present invention relates to a method for the production of a stable biodegradable, high water absorbable γ-polyglutamic acid (γ-PGA) hydrogel by directly cross-linking (A) a γ-polyglutamic acid (γ-PGA), a γ-polyglutamate, or a mixture thereof, and optionally a polysaccharide containing a carboxylic and/or carboxylate group, an amino acid, or a mixture thereof; and/or (B) a microbial culture broth containing a γ-polyglutamic acid (γ-PGA), a γ-polyglutamate, or a mixture thereof, and optionally a polysaccharide containing a carboxylic and/or carboxylate group, an amino acid, or a mixture thereof, with a cross-linker comprising a compound having three or more functional groups or a mixture of a compound having three or more functional groups and a compound having two functional groups, wherein each of the functional groups can react with a carboxylic group (—COOH), carboxylate group (—COO − ), aldehyde group (—CHO), hydroxyl (—OH), carbonyl group (—CO), sulfone group (—SO 2 ), amino group (—NH 2 ) or nitro group (—NO 2 ), or a mixture thereof. The present invention further relates to a stable biodegradable, high water absorbable γ-polyglutamic acid (γ-PGA) hydrogel and its uses.
1. A method for the production of a biodegradable, water absorbable γ-polyglutamic acid (γ-PGA) hydrogel comprising directly cross-linking
(A) a mixture of γ-polyglutamic acid (γ-PGA) and a γ-polyglutamate and optionally a polysaccharide containing a carboxylic acid and/or carboxylate group, an amino acid, or a mixture thereof; and/or
(B) a microbial culture broth containing a mixture of a γ-polyglutamic acid (γ-PGA) and a γ-polyglutamate and optionally a polysaccharide containing a carboxylic acid and/or carboxylate group, an amino acid, or a mixture thereof; and
a cross-linker comprising a polyglycidyl ether having three or more functional groups, wherein each of the functional groups thereon can react with a carboxylic group (—COOH), carboxylate group (—COO − ), aldehyde group (—CHO), hydroxyl (—OH), carbonyl group (—CO), sulfone group (SO 2 ), amino group (—NH 2 ) or nitro group (—NO 2 ), or a mixture thereof; wherein said polyglycidyl ether is glycerol triglycidyl ether, di- or polyglycerol polyglycidyl ether, polyoxyethylene sorbitol polyglycidyl ether, or a mixture thereof.
2. The method of claim 1 , wherein the polysaccharide is selected from the group consisting of a mixture of glucose, fructose, galactose, and glucuronic acid, and a mixture of rhamnose, glucose, galactose, and glucuronic acid, and a polycarboxylic acid in which hyaluronic acid as the principal component.
3. The method of claim 1 , wherein the amino acid is selected from the group consisting of polyaspartic acid, polylysine, aspartic acid, lysine and arginine, and a mixture thereof.
4. The method of claim 1 , wherein the polyglycidyl ether is glycerol triglycidyl ether.
5. The method of claim 1 , wherein the di- or polyglycerol polyglycidyl ether is a compound of Formula (I):
wherein R is H or
and n is 2 to 8.
6. The method of claim 5 , wherein n is 2 to 4.
7. The method of claim 1 , wherein the polyoxyethylene sorbitol polyglycidyl ether is a compound of Formula (II):
wherein R is H or
and x, y, z, o, p, and q are independently 1 to 3.
8. The method of claim 1 , wherein the amount of the cross-linker is 0.02 to 20 wt %, based on the total weight of (A) and (B).
9. The method of claim 8 , wherein the amount of the cross-linker is 0.25 to 6 wt %, based on the total weight of (A) and (B).
10. The method of claim 1 , wherein the cross-linking is conducted at a temperature of from 0° C. to 100° C.
11. The method of claim 10 , wherein the cross-linking is conducted at a temperature of from 35° C. to 85° C.
12. The method of claim 1 , wherein the cross-linking is conducted at a pH of from 3.3 to 8.5.
13. The method of claim 12 , wherein the cross-linking is conducted at a pH of from 4.0 to 8.5.