Compounds, nanoparticles, and pharmaceutical compositions for the treatment of drug addiction

Abstract

Provided herein are compounds of formula (I) or pharmaceutically acceptable salts thereof. Further disclosed are nanoparticles containing one compound and methods for treating drug addiction, drug dependence, drug overdose, opioid use disorder, pain, chronic pain, fibromyalgia, arthritis, or obesity using the same.

Claims

1. Equation (I): 【Chemistry 1】 A compound of or a pharmaceutically acceptable salt thereof, wherein the formula is: R is a C1-30 alkyl, C2-30 alkenyl, C1-30 heteroalkyl, C2-30 heteroalkenyl, phenyl, heteroaryl, or amino acid moiety; and A compound or a pharmaceutically acceptable salt thereof in which R' is hydrogen, a C1-6 alkyl group, a C1-6 heteroalkyl group, a C1-6 alkoxy group, a C1-6 heteroalkoxy group, or a C3-8 carboncyclic group.

2. The compound according to claim 1, wherein R' is hydrogen.

3. The compound according to claim 1, wherein R' is a C1-6 alkyl group.

4. The compound according to claim 3, wherein R' is methyl.

5. A compound according to any one of the preceding claims, wherein R is a C1-30 alkyl group.

6. The compound according to claim 5, wherein R is a C11-C19 alkyl group.

7. The compound according to claim 5, wherein R is a C13-C17 alkyl group.

8. The compound according to claim 5, wherein R is a C15 alkyl group.

9. The compound according to claim 5, wherein R is a C17 alkyl group.

10. The aforementioned compound is as follows: 【Chemistry 2】 The compound according to claim 1, or selected from a pharmaceutically acceptable salt thereof.

11. The aforementioned compound is as follows: 【Transformation 3】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof.

12. The aforementioned compound is as follows: 【Chemistry 4】 The compound according to claim 1, or a pharmaceutically acceptable salt thereof.

13. The compound according to any one of claims 1 to 12, wherein the compound complexes with a hydrophobic counterion selected from the group consisting of pamoic acid, myristic acid, palmitic acid, stearic acid, behenic acid, naphusylic acid, mandelic acid, tosylic acid, benzenesulfonic acid, benzoic acid, besylic acid, hydroxynaphthoic acid, and isethionic acid.

14. The compound according to any one of claims 1 to 12, wherein the pharmaceutically acceptable salt is pamoate.

15. Nanoparticles comprising a compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, and one or more polymers or surfactants.

16. Nanoparticles comprising a pharmaceutically acceptable salt of a compound according to any one of claims 1 to 12, and one or more polymers or surfactants.

17. The nanoparticle according to claim 16, wherein the pharmaceutically acceptable salt of the compound is pamoate.

18. The nanoparticle according to any one of claims 15 to 17, wherein the one or more polymers or surfactants are amphiphilic block copolymers.

19. The nanoparticle according to claim 18, wherein the amphiphilic block copolymer comprises at least one poly(oxyethylene) block and at least one poly(oxypropylene) block.

20. The nanoparticle according to claim 18, wherein the one or more polymers or surfactants are poloxamers.

21. The nanoparticle according to claim 18, wherein the one or more polymers or surfactants are P407.

22. The nanoparticles according to any one of claims 15 to 17, wherein the one or more polymers or surfactants comprise a poly(oxyethylene)sorbitan fatty acid ester.

23. The nanoparticles according to claim 22, wherein the one or more polymers or surfactants comprise poly(oxyethylene)(20)sorbitan monolauric acid.

24. The nanoparticles according to claim 22 or 23, wherein the one or more polymers or surfactants further comprise polyethylene glycol (PEG).

25. The nanoparticles according to claim 24, further comprising one or more polymers or surfactants, wherein the nanoparticles further comprise PEG3350.

26. The nanoparticles according to any one of claims 15 to 17, wherein the one or more polymers or surfactants include polyethylene glycol (PEG).

27. The nanoparticles according to claim 26, wherein the one or more polymers or surfactants include PEG3350.

28. The nanoparticles according to any one of claims 15 to 27, wherein the diameter of the nanoparticles is approximately 100 nm to 1 μm.

29. A pharmaceutical composition comprising a compound according to any one of claims 1 to 14 or a pharmaceutically acceptable salt thereof, or nanoparticles according to any one of claims 15 to 28, and a pharmaceutically acceptable carrier.

30. A method for treating a subject requiring treatment for drug addiction, drug dependence, drug overdose, opioid use disorder, pain, chronic pain, fibromyalgia, arthritis, or obesity, the method comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 14 or a pharmaceutically acceptable salt thereof, nanoparticles according to any one of claims 15 to 28, or a pharmaceutical composition according to claim 29.

31. The method according to claim 30, wherein the disease or disorder is opioid use disorder.

32. The method according to claim 30, wherein the compound, nanoparticles, or composition is administered by injection.

33. The method according to claim 32, wherein the compound, nanoparticles, or composition is administered once every 1 to 12 months.

34. The method according to claim 32, wherein the compound, nanoparticles, or composition is administered once every three months.

35. The method according to claim 32, wherein the compound, nanoparticles, or composition is administered once every six months.

36. The method according to claim 32, wherein the compound, nanoparticles, or composition is administered once every nine months.

37. The method according to claim 32, wherein the compound, nanoparticles, or composition is administered once every 12 months.

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