Vaginal hydrogel
View Patent ↗The vaginal hydrogel may be a composition which includes a glycosaminoglycan, a reactive molecule, and, in some embodiments, a therapeutic agent. The glycosaminoglycan and the reactive molecule may include either thiol groups or thiol reactive sites and have a pH that is within a range of a normal vaginal environment. Some of the thiol groups may interact with the vaginal mucosa and allow the hydrogel to remain in the vagina for a longer period than existing compounds intended for intravaginal administration. Therapeutic agents may be included in the composition. In these embodiments, the hydrogel acts as a vehicle which delivers the therapeutic agent.
1. A crosslinked composition comprising:
a glycosaminoglycan comprising a plurality of thiol groups and having a thiol modification of about 0.1 to about 0.4 μmol thiol per mg of glycosaminoglycan, and
a molecule comprising poly(ethylene glycol),
wherein the poly(ethylene glycol) comprises at least two thiol-reactive sites,
wherein the molar ratio of the thiol groups to the thiol-reactive sites is at least 2:1,
wherein the composition has a pH between about 3.2 and about 4.5, wherein the glycosaminoglycan crosslinks to the poly(ethylene glycol), and wherein the composition comprises about 0.05 to about 0.2 μmol uncrosslinked thiol groups per mg of the glycosaminoglycan.
2. The composition of claim 1 wherein the glycosaminoglycan comprises a modified hyaluronic acid having a thiol modification of about 0.1 to about 0.3 μmol thiol per mg of hyaluronic acid.
3. The composition of claim 1 ,
wherein the glycosaminoglycan comprises a thiol-modified hyaluronic acid;
wherein the molar ratio of the thiol groups to the thiol-reactive sites is between about 2:1 and about 3:1; and
wherein the composition has a pH between about 3.5 and about 4.5.
4. The composition of claim 1 , wherein the at least two thiol-reactive sites are independently selected from the group consisting of acrylate, methacrylate, bromoacetate, iodoacetate, bromoacetamide, iodoacetamide, and maleimide.
5. The composition of claim 1 , wherein the molecule comprising poly(ethylene glycol) comprises poly(ethylene glycol) diacrylate or poly(ethylene glycol) bisbromoacetate.
6. The composition of claim 1 , further comprising a cationic polymer.
7. The composition of claim 6 , wherein the cationic polymer comprises a polylysine.
8. The composition of claim 1 , further comprising a mucoadhesive agent.
9. The composition of claim 8 , wherein the mucoadhesive agent is selected from the group consisting of methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose.
10. The composition of claim 1 , further comprising a therapeutic agent.
11. The composition of claim 10 , wherein the therapeutic agent comprises one or more of an antimicrobial agent, an antibacterial agent, an antiviral agent, an anti-inflammatory agent, a steroid, an estrogen, and an estrogen derivative.
12. A crosslinked composition comprising:
an anionic polysaccharide comprising a plurality of thiol groups and having a thiol modification of about 0.1 to about 0.4 μmol thiol per mg of polysaccharide;
a cationic polymer; and
a molecule comprising poly(ethylene glycol);
wherein the poly(ethylene glycol) comprises at least two thiol reactive sites,
wherein the molar ratio of the thiol groups to the thiol-reactive sites is at least 2:1,
wherein the composition has a pH between about 3.2 and about 4.5, wherein the anionic polysaccharide crosslinks to the poly(ethylene glycol), and wherein the composition comprises about 0.05 to about 0.2 μmol uncrosslinked thiol groups per mg of the anionic polysaccharide.
13. The composition of claim 12 , wherein the anionic polysaccharide comprises a modified hyaluronic acid.
14. The composition of claim 12 , wherein the anionic polysaccharide comprises a modified glycosaminoglycan.
15. The composition of claim 12 , further comprising a therapeutic agent.