Prodrugs of gamma-hydroxybutyric acid, compositions and uses thereof

• US 10,640,451 B2
• Filed: 10/15/2019
• Issued: 05/05/2020
• Est. Priority Date: 09/23/2015
• Status: Active Grant

• Current Assignee: XWPharma Ltd.
• Original Assignee: XW Laboratories, Inc.
• Inventors: Xiang, Jia-Ning, Xu, Xuesong, Zhang, Xuan
• Primary Examiner(s): Aulakh, Charanjit
• Application Number:
  US16/601,908
• Publication Number:
  US 20200039917A1
• Time in Patent Office: 203 Days
• Field of Search: 514547
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07B 59/001 Acyclic or carbocyclic compounds
• CPC Class Codes: C07C 229/08 the nitrogen atom of the amino group being further bound to hydrogen atoms
• CPC Class Codes: C07C 229/34 the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 229/36 with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
• CPC Class Codes: C07C 233/47 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 255/57 containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
• CPC Class Codes: C07C 2601/06 with a five-membered ring
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2601/16 the ring being unsaturated
• CPC Class Codes: C07C 271/22 to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07C 271/34 with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 317/14 : having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 317/44 : having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
• CPC Class Codes: C07C 69/22 : having three or more carbon atoms in the acid moiety
• CPC Class Codes: C07C 69/24 : esterified with monohydroxylic compounds
• CPC Class Codes: C07C 69/28 : esterified with dihydroxylic compounds
• CPC Class Codes: C07C 69/34 : Esters of acyclic saturated polycarboxylic acids having an esterified carboxyl group bound to an acyclic carbon atom
• CPC Class Codes: C07C 69/608 : Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a ring other than a six-membered aromatic ring in the acid moiety
• CPC Class Codes: C07C 69/612 : Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
• CPC Class Codes: C07C 69/618 : having unsaturation outside the six-membered aromatic ring
• CPC Class Codes: C07C 69/738 : Esters of keto-carboxylic acids or aldehydo-carboxylic acids
• CPC Class Codes: C07C 69/74 : Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 69/76 : Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 69/78 : Benzoic acid esters
• CPC Class Codes: C07C 69/96 : Esters of carbonic or haloformic acids
• CPC Class Codes: C07D 207/12 : Oxygen or sulfur atoms
• CPC Class Codes: C07D 207/16 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 211/44 : attached in position 4
• CPC Class Codes: C07D 211/46 : having a hydrogen atom as the second substituent in position 4
• CPC Class Codes: C07D 213/79 : Acids; Esters
• CPC Class Codes: C07D 213/80 : in position 3
• CPC Class Codes: C07D 277/30 : Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 277/56 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 307/68 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 309/12 : only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
• CPC Class Codes: C07D 317/64 : Oxygen atoms
• CPC Class Codes: C07D 333/38 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The present disclosure discloses prodrugs of gamma-hydroxybutyric acid as well as compositions and uses thereof.

Claims

1. A composition comprising a compound having the structure of Formula II:

2. The composition of claim 1, wherein the composition is a solid.

3. The composition of claim 1, wherein the composition further comprises a solvent for dissolving or dispersing the compound.

4. The composition of claim 3, wherein the solvent comprises water.

5. The composition of claim 1, wherein the composition is in a liquid dosage form.

6. The composition of claim 1, wherein the composition further comprises a flavoring agent, sucrose, lactose, cellulose sugar, mannitol, maltitol, dextran, sorbitol, starch, agar, alginates, chitins, chitosans, pectins, tragacanth gum, gum arabic, gelatins, collagens, casein, albumin, synthetic or semi-synthetic polymers or glycerides, methyl cellulose, hydroxypropylmethyl-cellulose, or polyvinylpyrrolidone.

7. The composition of claim 1, wherein the composition further comprises a polymeric excipient.

8. The composition of claim 1, wherein the composition comprises a tablet, a caplet, a capsule, a gel cap, granules, a pill, a powder, a lozenge, a sachet, a cachet, a suspension, an emulsion, a solution, a slurry, or a syrup.

9. The composition of claim 1, wherein the composition is formulated in a unit dosage form.

10. The composition of claim 9, wherein the unit dosage form has a weight from 0.5 grams to 30 grams.

11. The composition of claim 10, wherein the composition is in a liquid dosage form.

12. The composition of claim 11, further comprising a pH adjusting agent selected from sodium hydroxide, hydrochloric acid, or malic acid.

13. The composition of claim 1, wherein the composition is formulated in a form comprising a quick release form.

14. The composition of claim 1, wherein the composition is formulated in a form comprising a delayed release form.

15. The composition of claim 1, wherein the composition is formulated in a form comprising a sustained-release form.

16. The composition of claim 1, wherein the composition consists of a compound having the structure of Formula II:

17. The composition of claim 16, wherein the composition consists of a compound having the structure of Formula II:

18. A method of treating a subject in need thereof, wherein the method comprises administering to the subject a pharmaceutically effective amount of a composition comprising a compound having the structure of Formula II:

19. The method of claim 18, wherein the disease or condition is narcolepsy.

20. The method of claim 18, wherein the disease or condition is excessive daytime sleepiness.

21. The method of claim 18, wherein the disease or condition is cataplexy.

22. The method of claim 18, wherein administering to the subject the pharmaceutically effective amount of the composition comprises administering the composition no more than one time per day.

23. The method of claim 18, wherein administering to the subject the pharmaceutically effective amount of the composition comprises administering the composition orally, nasally, intravenously, subcutaneously, or intramuscularly.

24. The method of claim 23, wherein administering to the subject the pharmaceutically effective amount of the composition comprises administering the composition orally.

25. The method of claim 24, wherein administering the composition orally comprises administering the composition in an emulsion, syrup, elixir, suspension, slurry, or solution.

26. The method of claim 25, wherein administering the composition orally comprises administering the composition in a solution.

27. The method of claim 18, wherein administering to the subject the pharmaceutically effective amount of the composition comprises administering from 0.5 grams to 30 grams of the composition.

28. The method of claim 18, wherein administering to the subject the pharmaceutically effective amount of the composition comprises administering a quick-release form comprising the composition.

29. The method of claim 18, wherein administering to the subject the pharmaceutically effective amount of the composition comprises administering a sustained-release form comprising the composition.

30. The method of claim 18, wherein administering to the subject the pharmaceutically effective amount of the composition comprises administering a delayed-release form comprising the composition.