Pharmaceutical salts/co-crystals of pentoxifylline, clonidine and linsidomine with caffeic, protocatechuic or alpha-lipoic acid an use thereof for treatment of pain

Patent metadata

Field	Value
Publication number	US-11510926-B2
Application number	US-201917058161-A
Country	US
Kind code	B2
Filing date	May 27, 2019
Priority date	May 31, 2018
Publication date	Nov 29, 2022
Grant date	Nov 29, 2022

Abstract

Disclosed are pharmaceutical salts and co-crystals of pentoxifylline, clonidine and linsidomine with caffeic acid, protocatechuic acid or α-lipoic acid, and method for preparing thereof. Also disclosed are topical compositions comprising said salts or co-crystals and use thereof for treating pain.

First claim

The invention claimed is:

1. A compound salt/co-crystal selected from pentoxifylline caffeate, pentoxifylline protocatechuate, clonidine α-lipoate and linsidomine caffeate or a solvate thereof.

2. The compound of claim 1 which is pentoxifylline caffeate.

3. The compound of claim 1 which is pentoxifylline protocatechuate.

4. The compound of claim 1 which is clonidine α-lipoate.

5. The compound of claim 1 which is clonidine α-lipoate as an ethanol solvate.

6. The compound of claim 1 which is linsidomine caffeate.

7. A composition comprising a compound salt/co-crystal as defined in claim 1 and a pharmaceutically acceptable diluent or carrier.

8. A method for preventing or treating pain comprising topically administering an effective amount of a salt/co-crystal selected from pentoxifylline caffeate, pentoxifylline protocatechuate, clonidine α-lipoate and linsidomine caffeate or a solvate thereof to a subject in need thereof.

9. The method of claim 8 wherein said the pain is neuropathic, ischemic, muscle pain, pain associated with peripheral nerve injury induced by trauma, metabolic dysfunction, chemotherapy, viral or bacterial disease, nerve compression or neurologic conditions, or pain associated with angina, peripheral arterial disease, fibromyalgia, or conditions involving mixed inflammatory and neuropathic pain.

10. The method of claim 8 further comprising administering an effective amount of at least another agent useful for preventing or treating pain to a subject in need thereof.

11. The method of claim 10 wherein said another agent is administered concurrently or sequentially with the salt/co-crystal or a solvate thereof.

12. The method of claim 10 , wherein said another agent is a cyclooxygenase inhibitor, a non-steroidal anti-inflammatory drugs (NSAIDs), a peripheral analgesic agent, a narcotic analgesic, an NMDA receptor antagonist, a tricyclic antidepressant, an α2δ calcium channel agent, or a sympathetic blocking agent, or a combination thereof.

13. A method for preparing pentoxifylline caffeate, pentoxifylline protocatechuate, clonidine α-lipoate or linsidomine caffeate salt/co-crystal or a solvate thereof, comprising liquid-assisted grinding of an equimolar quantities of pentoxifylline with caffeic acid, pentoxifylline with protocatechuic acid, clonidine with α-lipoic acid or a caffeate salt with a linsidomine salt.

14. The method of claim 13 , wherein said grinding is conducted in a jar together with one or more grinding balls.

15. The method of claim 13 , wherein said liquid is ethanol or nitromethane.

16. The method of claim 13 wherein said caffeate salt is sodium caffeate.

17. The method of claim 13 wherein said linsidomine salt is linsidomine chloride.

Assignees

• The Royal Institution For The Advancement Of Learning/Mcgill Univ

Inventors

• Coderre Terence J
• Fulas Oli Abate
• Laferrière André
• Ayoub Ghada
• Fri{Hacek Over (S)}{Hacek Over (C)}Ić Tomislav
• Gandrath Dayaker
• Mottillo Cristina

Classifications

• A61K31/5377 Primary

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/4168

  having a nitrogen attached in position 2, e.g. clonidine · CPC title

• C07D271/04

  1,2,3-Oxadiazoles; Hydrogenated 1,2,3-oxadiazoles · CPC title

• A61K31/522

  having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir · CPC title

• A61P29/02

  without antiinflammatory effect · CPC title