Methods for treating interstitial cystitis
Described herein are methods for treating interstitial cystitis in a subject comprising administering to the subject an effective amount of a compound which is a modified hyaluronan or a pharmaceutically acceptable salt or ester thereof, wherein said hyaluronan or its pharmaceutically acceptable salt or ester comprises at least one sulfate group and the primary C-6 hydroxyl proton of at least one N-acetyl-glucosamine residue is substituted with an unsubstituted alkyl group or fluoroalkyl group.
1. A method for treating interstitial cystitis in a subject comprising administering to the subject an effective amount of a compound which is
a modified hyaluronan or a pharmaceutically acceptable salt or ester thereof, wherein said hyaluronan or its pharmaceutically acceptable salt or ester comprises at least one sulfate group and the primary C-6 hydroxyl proton of at least one N-acetyl-glucosamine residue is substituted with a C 1 -C 10 unsubstituted alkyl group or fluoroalkyl group.
2. The method of claim 1 , wherein the unsubstituted alkyl group is methyl.
3. The method of claim 1 , wherein the fluoroalkyl group has at least one trifluoromethyl group.
4. The method of claim 1 , wherein from 1% to 100% of the primary C-6 hydroxyl protons of the N-acetyl-glucosamine residues are substituted with an unsubstituted alkyl group or fluoroalkyl group.
5. The method of claim 1 , wherein the hyaluronan has a molecular weight less than 10 kDa prior to alkylation, fluoroalkylation, and sulfation.
6. The method of claim 1 , wherein the hyaluronan has a molecular weight from 10 kDa to 2,000 kDa prior to alkylation, fluoroalkylation, and sulfation.
7. The method of claim 1 , wherein at least one C-2 hydroxyl proton and C-3 hydroxyl proton is substituted with a sulfate group.
8. The method of claim 1 , wherein the C-4 hydroxyl proton of the N-acetyl glucosamine residue is substituted with a sulfate group, the C-2 hydroxyl proton of the glucuronic acid residue is substituted with a sulfate group, the C-3 hydroxyl proton of the glucuronic acid residue is substituted with a sulfate group, or any combination thereof.
9. The method of claim 1 , wherein the compound has a degree of sulfation from 0.5 to 4.0 per disaccharide unit.
10. The method of claim 1 , wherein the alkyl group is methyl and at least one C-2 hydroxyl proton and/or C-3 hydroxyl proton is substituted with a sulfate group.
11. The method of claim 1 , wherein the alkyl group is methyl, at least one C-2 hydroxyl proton and/or C-3 hydroxyl proton is substituted with a sulfate group, and the compound has a molecular weight of 2 kDa to 10 kDa.
12. The method of claim 1 , wherein the compound is administered as a pharmaceutical composition.
13. The method of claim 12 , wherein the composition is formulated into a capsule, a tablet, a chewing gum, a lozenge, a powder, beverage, an ointment, a lotion, a cream, a gel, drops, a suppository, a spray, a liquid or a powder.
14. The method of claim 12 , wherein the composition is administered intravenously, intramuscularly, subcutaneously, by ingestion, or topically.
15. The method of claim 12 , wherein the composition is administered topically, wherein the topical administration comprises is transbuccal, sublingual, oral, vaginal, intranasal, rectal, or by intravesical instillation.
16. The method of claim 12 , wherein the composition further comprises an anti-inflammatory agent, an anti-pyretic agent, steroidal and non-steroidal drugs for anti-inflammatory use, a hormone, a growth factor, a contraceptive agent, an antiviral, an antibacterial, an antifungal, an analgesics, a hypnotic, a sedative, a tranquilizer, an anti-convulsant, a muscle relaxant, a local anesthetic, an antispasmodic, an antiulcer drug, a sympathiomimetic agent, a cardiovascular agent, an antitumor agent, or an oligonucleotide.
17. The method of claim 1 , wherein the pharmaceutically acceptable salt is an organic salt, a metal salt, or a combination thereof.
18. The method of claim 1 , wherein the pharmaceutically acceptable salt is a salt selected from the group consisting of NH 4 + , Na + , Li + , K + , Ca +2 , Mg +2 , Fe +2 , Fe +3 , Cu +2 , Al +3 , Zn +2 , 2-trimethylethanolammonium cation (choline), or a quaternary salt of isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, lysine, arginine, and histidine.
19. The method of claim 1 , wherein the administration of the compound inhibits the activity of LL-37 (SEQ. ID. NO. 1) in the subject.