Methods for the formation of hydrogels using thiosulfonate compositions and uses thereof
View Patent ↗The present invention provides both crosslinked polymer compositions capable of forming hydrogels upon exposure to an aqueous environment and thiosulfonate hydrogel-forming components. The thiosulfonate hydrogel-forming components of the invention are preferably multi-arm thiosulfonate polymer derivatives that form a crosslinked polymer composition when exposed to a base without requiring the presence of a second cross-linking reagent, redox catalyst, or radiation. Methods for forming hydrogel compositions, as well as methods for using the hydrogels, are also provided.
1. A hydrogel composition comprising comprising an active agent and crosslinked thiosulfonate derivatives, wherein each thiosulfonate derivative, prior to being crosslinked, has the formula:
wherein:
POLY is a water-soluble polymer;
(n) is 3 to about 25;
X is a linking group;
Y is moiety derived from a molecule having at least three nucleophilic groups, and R is an organic radical;
POLY' is water-soluble polymer (either the same or different than POLY);
Z is a functional group having low reactivity with thiosulfonate, sulfhydryl, and disfulde linkages; and
(m) is a positive integer.
2. The hydrogel composition of claim 1 , wherein both POLY and POLY' are the water-soluble poly(ethylene glycol)s.
3. The hydrogel composition of claim 1 , wherein (n) is 3 to 10.
4. The hydrogel composition of claim 3 , wherein (n) is 3.
5. The hydrogel composition of claim 3 , wherein (n) is 4.
6. The hydrogel composition of claim 3 , wherein (n) is 5.
7. The hydrogel composition of claim 6 , wherein (n) is 6.
8. The hydrogel composition of claim 1 , wherein the organic radical is alkyl or aryl.
9. The hydrogel composition of claim 1 , wherein the organic radical is methyl.
10. The hydrogel composition of claim 1 , wherein the organic radical is phenyl.
11. The hydrogel composition of claim 2 , wherein each of the poly(ethylene glycol)s has a molecular weight of from 200 Da to about 20,000 Daltons.
12. The hydrogel composition of claim 11 , wherein each of the poly(ethylene glycol)s has a molecular weight of from 500 Da to about 15,000 Daltons.
13. The hydrogel composition of claim 11 , wherein each of the poly(ethylene glycol)s has a molecular weight of from 600 Da to about 6,000 Daltons.
14. The hydrogel composition of claim 1 , wherein the molecule having at least three nucleophilic groups is selected from the group consisting of glycerol, oligoglycerols, pentaerythritol, carbohydrates, and cyclodextrin.
15. The hydrogel composition of claim 1 , wherein the molecule having at least three nucleophilic groups is glycerol.
16. The hydrogel composition of claim 1 , wherein the molecule having at least three nucleophilic groups is an oligoglycerol.
17. The hydrogel composition of claim 1 , wherein the molecule having at least three nucleophilic groups is
18. The hydrogel composition of claim 1 , wherein the molecule having at least three nucleophilic groups is pentaerythritol.
19. The hydrogel composition of claim 1 , wherein the molecule having at least three nucleophilic groups is 1,2,3-propane-triamine.
20. The hydrogel composition of claim 1 , wherein (m), is selected from the group consisting of 1, 2, 3, 5 and 10.
21. The hydrogel composition of claim 1 , wherein the active agent is a non-steroidal anti-inflammatory drug.