Treatment of vulvar pain

Patent metadata

Field	Value
Publication number	US-11400057-B2
Application number	US-201916590973-A
Country	US
Kind code	B2
Filing date	Oct 2, 2019
Priority date	Oct 19, 2018
Publication date	Aug 2, 2022
Grant date	Aug 2, 2022

Abstract

The present invention relates to methods of treating female reproductive tract irritation (such as pain and pruritus) or/and inflammation.

First claim

What is claimed is:

1. A method of reducing, preventing, or treating vulvodynia in a subject, comprising administering to a subject in need an effective amount of a compound having the Formula (I):

wherein is a double bond with the Z or E configuration;
wherein

with the Z or E configuration; wherein the carbon at C7 and C14 are, independently, either R or S;
wherein R 1 , is selected from hydrogen, (C1-C6) alkyl, glyceryl, (C3-C8) cycloalkyl, cyclohexyl, (C4-C11) cycloalkylalkyl, (C5-C15) aryl, (C6-C16) arylalkyl, 2-6 membered heteroalkyl, 3-8 membered cycloheteroalkyl, 4-11 membered cycloheteroalkylalkyl, (C5-C14) heteroaryl and 6-21 membered heteroarylalkyl;
wherein each of R 2 and R 2′ is independently a hydroxyl group or a hydrogen atom, with the proviso that at least one of R 2 and R 2′ is a hydroxyl group;
wherein R 3 , if present, is selected from hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, (C4-C11) cycloalkylalkyl, (C5-C15) aryl, (C6-C16) arylalkyl, and 2-6 membered heteroalkyl;
wherein R 3′ is selected from hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, (C4-C11) cycloalkylalkyl, (C5-C15) aryl, (C6-C16) arylalkyl, and 2-6 membered heteroalkyl;
or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein compounds of Formula (I) are in the triglyceride, diglyceride and/or monoglyceride form.

3. The method of claim 1 , wherein R 1 is methyl or ethyl.

4. The method of claim 1 , wherein the compound of Formula (I) is selected from: Maresin 1, 7S-Maresin 1, 14S-methyl-Maresin 1, 14R-methyl-Maresin 1, 14R/S-methyl-Maresin 1, 7R,14S-dihydroxi-7,14-dimethyl-docosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid, 7R-methyl-Maresin 1, 7S-methyl-Maresin 1, 7S,14S-diHDHA, 14S-HDHA, 14R-HDHA, 14R-methyl-HDHA, 14S-methyl-HDHA or a pharmaceutically acceptable salt or ester thereof.

5. The method of claim 1 , wherein the compound of Formula (I) is selected from: 14S-methyl-Maresin 1, 14R-methyl-Maresin 1, 14R/S-methyl-Maresin 1, 7R,14S-dihydroxi-7,14-dimethyl-docosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid, or a pharmaceutically acceptable salt or ester thereof.

6. The method of claim 1 , wherein the compound of Formula (I) is selected from: 14S-HDHA, 14R-HDHA, 14S/R-HDHA, and a pharmaceutically acceptable salt or ester thereof.

7. The method of claim 1 , wherein the vulvodynia is localized provoked vulvodynia.

8. The method of claim 1 , wherein the compound of Formula (I) is administered at 0.0001 mg/kg-100 mg/kg.

9. The method of claim 1 , wherein the compound of Formula (I) is administered once a week, 2-3 times a week, once a day, twice a day, or three times a day.

10. The method of claim 1 , wherein the compound of Formula (I) is administered before the subject is exposed to a secondary pain-causing stimulation.

11. The method of claim 1 , wherein the treatment site comprises the vulvar vestibule.

12. The method of claim 1 , wherein the at least one compound of Formula (I) is administered with at least one additional therapeutic agent, said at least one additional therapeutic agent is one or more specialized pro-resolving mediators (SPMs) or one or more SPM precursors not included in Formula (I), an anti-microbial agent, or an antiviral agent.

13. The method of claim 1 , wherein the at least one compound of Formula (I) is administered with at least one additional therapeutic agent, said at least one additional therapeutic agent is one or more specialized pro-resolving mediators (SPMs) or one or more SPM precursors not included in Formula (I).

14. The method of claim 12 , wherein the SPMs or SPM precursors not included in Formula (I) are 17-HDHA and 18-HEPE; or a pharmaceutically acceptable salt or ester thereof.

15. The method of claim 1 , wherein compound of Formula (I) or a composition thereof is topical administered.

Assignees

• Univ Rochester

Inventors

• Foster David
• Falsetta Wood Megan L
• Phipps Richard P

Classifications

• A61P15/02

  for disorders of the vagina · CPC title

• A61K9/12

  Aerosols; Foams {(A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015)} · CPC title

• A61K9/1605

  Excipients; Inactive ingredients · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K9/02

  Suppositories; Bougies; Bases therefor; {Ovules}(apparatus for making A61J3/08; devices for introducing into the body A61M31/00) · CPC title