In situ crosslinking hydrogel comprising γ-polyglutamic acid and method for producing the same

1. A γ-polyglutamic acid derivative of chemical formula 1:

wherein,

a total sum of l, m, and n is an integer of 390 to 15,500,

a ratio of l, m, and n is I:m:n=0 to 0.5:0.2 to 0.5:0.2 to 0.8,

L is a linker, M is each independently H, an alkali metal or alkali earth metal, R is CH 2 ,

b is 0 or 1, and c is an integer of 1 to 5.

2. The γ-polyglutamic acid derivative of claim 1 , wherein the linker is —HN—(R)a-O—, wherein R is CH 2 and a is an integer of 1 to 5.

3. The γ-polyglutamic acid derivative of claim 2 , wherein the linker is derived from aminomethanol, 1-amino-2-propanol,1-amino-3-propanol, 1-amino-4-butanol, 1-amino-5-pentanol, or 2-aminoethanol.

4. The γ-polyglutamic acid derivative of claim 1 , wherein —(CO)b-(R)c-CO— is —CH 2 CH 2 CH 2 CH 2 —CO—, —CO—CH 2 CH 2 CH 2 —CO—, —CH 2 CH 2 —CO—, —CO—CH 2 CH 2 —CO—, or —CH 2 —CO—.

5. A method of preparing the γ-polyglutamic acid derivative of claim 1 , which comprises

a first step of reacting a γ-polyglutamic acid with a lower alkanolamine having 1to 5 carbon atoms to form a γ-polyglutamic acid-alkanolamine;

a second step of reacting the γ-polyglutamic acid-alkanolamine with an anhydride of an acid selected from the group consisting of glutaric acid and succinic acid, or 1-halo alkanoic acid selected from the group consisting of 1-halo valeric acid, 1-halo propionic acid and 1-halo methylcarbonic acid to form a carboxyl terminal to which an alkyl group is attached; and

a third step of reacting the thus formed carboxyl terminal with N-hydroxysuccinimide or N-hydroxysulfosuccinimide to form the γ-polyglutamic acid derivative.

6. The method of preparing the γ-polyglutamic acid derivative according to claim 5 , wherein in the first step, the lower alkanolamine is reacted in a molar ratio of 0.1 to 2 with regard to a mole unit of the carboxyl groups of the γ-polyglutamic acid.

7. The method of preparing the γ-polyglutamic acid derivative according to claim 5 , wherein in the second step, the anhydride of an acid or 1-halo alkanoic acid is reacted in a molar ratio of 3 to 8 with regard to a mole unit of the lower alkanolamine which forms the γ-polyglutamic acid-alkanolamine.

8. The method of preparing the y-polyglutamic acid derivative according to claim 5 , wherein in the third step, the N-hydroxysuccinimide or N-hydroxysulfosuccinimide is reacted in a molar ratio of 0.1 to 3 with regard to a mole unit of the formed carboxyl terminal.

9. A hydrogel comprising a crosslinked body obtained by crosslinking the γ-polyglutamic acid derivative of claim 1 , and a polyethylene glycol based polymer having a plurality of nucleophilic functional groups.

10. The hydrogel of claim 9 , wherein the nucleophilic functional groups are an amine group, thiol group, or hydroxyl group.

11. The hydrogel of claim 9 , wherein the polyethylene glycol based polymer is represented by chemical formula 2:

I—[(CH 2 CH 2 O) n —CH 2 CH 2 X] m   Chemical formula 2

wherein, I is a radical derived from 2 to 12 polyhydric alcohol, X represents an amine group, thiol group or hydroxyl group, n is 19 to 170, and m is an integer of 2 to 12, which is equal to the number of the hydroxyl groups of the polyhydric alcohol which I is derived from.

12. The hydrogel of claim 11 , wherein the polyethylene glycol based polymer is represented by chemical formula 3 or 4:

wherein X represents an amine group, thiol group or hydroxyl group, and n is 19 to 170.

13. The method of claim 5 , wherein the linker is —HN—(R)a-O—, wherein R is CH 2 and a is an integer of 1 to 5.

14. The method of claim 13 , wherein the linker is derived from aminomethanol, 1-amino-2-propanol, 1-amino-3-propanol, 1-amino-4-butanol, 1-amino-5-pentanol, or 2-aminoethanol.

15. The method of claim 5 , wherein —(CO)b-(R)c-CO—is —CH 2 CH 2 CH 2 CH 2 —CO—, —CO—CH 2 CH 2 CH 2 —CO—, —CH 2 CH 2 —CO—, —CO—CH 2 CH 2 —CO—, or—CH 2 —CO—.

16. The hydrogel of claim 9 , wherein the linker is —HN—(R)a-O—, wherein R is CH 2 and a is an integer of 1 to 5.

17. The hydrogel of claim 16 , wherein the linker is derived from aminomethanol, 1-amino-2-propanol, 1-amino-3-propanol, 1-amino-4-butanol, 1-amino-5-pentanol, or 2-aminoethanol.

18. The hydrogel of claim 9 , wherein —(CO)b-(R)c-CO—is —CH 2 CH 2 CH 2 CH 2 —CO—, —CO—CH 2 CH 2 CH 2 —CO—, —CH 2 CH 2 —CO—, —CO—CH 2 CH 2 —CO—, or —CH 2 —CO—.

19. A γ-polyglutamic acid derivative comprising a repeating unit of chemical formula 5, a repeating unit of chemical formula 6 and a repeating unit of chemical formula 7:

-(A) l -  Chemical formula 5

—(B) m —  Chemical formula 6

—(C) n —  Chemical formula 7

wherein,

A is

B is

 and

C is

where a total sum of I, m, and n is an integer of 390 to 15,500,

a ratio of I to m to n is 0 to 0.5:0.2 to 0.5:0.2 to 0 . 8 ,

L is a linker, M is each independently H, an alkali metal or alkali earth metal, R is CH 2 ,

b is 0 or 1, and

c is an integer of 1 to 5.