Compositions and methods for treatment of ocular diseases
The present disclosure relates to compositions and methods for treating ocular diseases with antibiotics. In particular, the disclosure relates to non-blurring, antibiotic-containing hydrogel compositions that have an extended contact time on the eye and do not interfere with wound healing.
1. An ocular composition, comprising:
a shear-thinning hydrogel comprising a thiolated hyaluronic acid (HA), wherein the thiolated HA is at a concentration of about 3 to about 8 mg/ml and is covalently crosslinked, and a thiol modification of the thiolated HA is between about 0.05 to about 0.15 μmol thiol/mg; and
an antibiotic at a concentration of about 1 to about 10 mg/ml,
wherein the ocular composition is in the form of an eyedrop.
2. The ocular composition of claim 1 , wherein the thiolated hyaluronic acid is at a concentration of about 3, 4, 5, 6, 7, or 8 mg/ml.
3. The ocular composition of claim 1 , wherein the antibiotic is at a concentration of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 mg/ml.
4. The ocular composition of claim 1 , wherein the antibiotic has a solubility in water of about 1 mg/ml or greater.
5. The ocular composition of claim 1 , wherein the antibiotic is a fluoroquinolone.
6. The ocular composition of claim 5 , wherein the antibiotic is moxifloxacin or a salt of moxifloxacin.
7. The ocular composition of claim 6 , wherein the antibiotic is moxifloxacin hydrochloride.
8. The ocular composition of claim 5 , wherein the antibiotic is a salt of besifloxacin.
9. The ocular composition of claim 8 , wherein the antibiotic is besifloxacin hydrochloride.
10. The ocular composition of claim 1 , wherein the antibiotic is an aminoglycoside.
11. The ocular composition of claim 10 , wherein the antibiotic is tobramycin.
12. The ocular composition of claim 1 , wherein the thiolated hyaluronic acid is thiolated carboxymethyl hyaluronic acid.
13. The ocular composition of claim 1 , wherein the hydrogel is disulfide crosslinked.
14. The ocular composition of claim 12 , wherein the hydrogel is disulfide crosslinked.
15. An ocular composition, comprising:
a shear-thinning hydrogel comprising thiolated hyaluronic acid (HA), wherein the thiolated HA is at a concentration of about 3 to about 8 mg/ml and is disulfide crosslinked, and a thiol modification of the thiolated HA is between about 0.05 to about 0.15 μmol thiol/mg; and
an antibiotic at a concentration of about 1 to about 10 mg/ml,
wherein upon application, the shear-thinning hydrogel resides on an eye of a patient for between about 30 minutes and about 2 hours, and
wherein the ocular composition is in the form of an eyedrop.
16. The ocular composition of claim 15 , wherein the thiolated hyaluronic acid is at a concentration of 3, 4, 5, 6, 7, or 8 mg/ml.
17. The ocular composition of claim 15 , wherein the antibiotic is at a concentration of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 mg/ml.
18. The ocular composition of claim 15 , wherein the thiolated hyaluronic acid is at a concentration of about 6.5 to about 8.0 mg/ml.
19. The ocular composition of claim 15 , wherein the antibiotic is a fluoroquinolone.
20. The ocular composition of claim 19 , wherein the antibiotic is a salt of moxifloxacin.
21. The ocular composition of claim 20 , wherein the antibiotic is moxifloxacin hydrochloride.
22. The ocular composition of claim 15 , wherein the thiolated HA is thiolated carboxymethyl HA (CMHA-S).
23. The ocular composition of claim 22 , which upon application remains in contact with an eye surface for at least 30 minutes and up to two hours.
24. The ocular composition of claim 22 , wherein the CMHA-S is at a concentration of about 7 to about 8 mg/ml.
25. The ocular composition of claim 1 , wherein the thiolated HA is at a concentration of about 7 to about 8 mg/ml.
26. The ocular composition of claim 1 , wherein the thiolated HA is thiolated carboxymethyl HA (CMHA-S), and wherein the hydrogel has a viscosity of 0.9-3.6 Pa.s, measured at a shear rate of 2.5 Hz.
27. The ocular composition of claim 22 , wherein the hydrogel has a viscosity of 0.9-3.6 Pa.s, measured at a shear rate of 2.5 Hz.