Mesophasic forms of (3S)-aminomethyl-5-methyl-hexanoic acid prodrugs and methods of use

1. A mesophasic form of calcium (3S)-{[(1R)-isobutanoyloxyethoxy]carbonylaminomethyl}-5-methyl-hexanoate, which exhibits characteristic scattering angles (2θ) at least at 5.4°±0.2° and 14.1°±0.2° in an X-ray powder diffractogram measured using Cu—K α radiation.

2. The mesophasic of claim 1 , which exhibits a melting point range from 102° C. to 111° C.

3. A pharmaceutical composition comprising the mesophasic form of claim 1 and a pharmaceutically acceptable vehicle.

4. The pharmaceutical composition of claim 3 , comprising a therapeutically effective amount of the mesophasic form for treating a disease or disorder in a patient, wherein the disease or disorder is chosen from post-operative pain, chemotherapy-induced pain, general anxiety disorder, post-herpetic neuralgia, painful diabetic peripheral neuropathy, sleep disorders, fibromyalgia, restless legs syndrome, pain associated with spinal cord injury, social phobia, perioperative pain, acute post-surgical pain, opioid use, neuropathic pain, musculoskeletal pain, chronic pain, osteoarthritis pain, muscle pain, migraine, hot flashes, faintness attacks, urinary incontinence, ethanol withdrawal syndrome, and premature ejaculation.

5. The pharmaceutical composition of claim 3 , wherein the pharmaceutical composition is a sustained release oral dosage formulation.

6. A method of treating a disease or disorder in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the pharmaceutical composition of claim 3 , wherein the disease or disorder is chosen from post-operative pain, chemotherapy-induced pain, general anxiety disorder, post-herpetic neuralgia, painful diabetic peripheral neuropathy, sleep disorders, fibromyalgia, restless legs syndrome, pain associated with spinal cord injury, social phobia, perioperative pain, acute post-surgical pain, opioid use, neuropathic pain, musculoskeletal pain, chronic pain, osteoarthritis pain, muscle pain, migraine, hot flashes, faintness attacks, urinary incontinence, ethanol withdrawal syndrome, and premature ejaculation.

7. A kit comprising the pharmaceutical composition of claim 3 and instructions for administering the pharmaceutical composition to a patient in need thereof for treating a disease or disorder chosen from post-operative pain, chemotherapy-induced pain, general anxiety disorder, post-herpetic neuralgia, painful diabetic peripheral neuropathy, sleep disorders, fibromyalgia, restless legs syndrome, pain associated with spinal cord injury, social phobia, perioperative pain, acute post-surgical pain, opioid use, neuropathic pain, musculoskeletal pain, chronic pain, osteoarthritis pain, muscle pain, migraine, hot flashes, faintness attacks, urinary incontinence, ethanol withdrawal syndrome, and premature ejaculation.

8. The pharmaceutical composition of claim 3 , comprising an agent chosen from an opioid agonist, a selective serotonin re-uptake inhibitor, and a selective noradrenaline re-uptake inhibitor.

9. A mesophasic form of calcium (3S)-{[(1S)-isobutanoyloxyisobutoxy]carbonylaminomethyl}-5-methyl-hexanoate, which exhibits characteristic scattering angles (2θ) at least at 5.1°±0.2° in an X-ray powder diffractogram measured using Cu—K α radiation.

10. The mesophasic form of claim 9 , which exhibits a melting point range from 90° C. to 104° C.

11. A pharmaceutical composition comprising the mesophasic form of claim 9 and a pharmaceutically acceptable vehicle.

12. The pharmaceutical composition of claim 11 , comprising a therapeutically effective amount of the mesophasic form of claim 9 for treating a disease or disorder in a patient, wherein the disease or disorder is chosen from post-operative pain, chemotherapy-induced pain, general anxiety disorder, post-herpetic neuralgia, painful diabetic peripheral neuropathy, sleep disorders, fibromyalgia, restless legs syndrome, pain associated with spinal cord injury, social phobia, perioperative pain, acute post-surgical pain, opioid use, neuropathic pain, musculoskeletal pain, chronic pain, osteoarthritis pain, muscle pain, migraine, hot flashes, faintness attacks, urinary incontinence, ethanol withdrawal syndrome, and premature ejaculation.

13. The pharmaceutical composition of claim 11 , wherein the pharmaceutical composition is a sustained release oral dosage formulation.

14. A method of treating a disease or disorder in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the pharmaceutical composition of claim 11 , wherein the disease or disorder is chosen from post-operative pain, chemotherapy-induced pain, general anxiety disorder, post-herpetic neuralgia, painful diabetic peripheral neuropathy, sleep disorders, fibromyalgia, restless legs syndrome, pain associated with spinal cord injury, social phobia, perioperative pain, acute post-surgical pain, opioid use, neuropathic pain, musculoskeletal pain, chronic pain, osteoarthritis pain, muscle pain, migraine, hot flashes, faintness attacks, urinary incontinence, ethanol withdrawal syndrome, and premature ejaculation.

15. A kit comprising the pharmaceutical composition of claim 11 and instructions for administering the pharmaceutical composition to a patient in need thereof for treating a disease or disorder chosen from post-operative pain, chemotherapy-induced pain, general anxiety disorder, post-herpetic neuralgia, painful diabetic peripheral neuropathy, sleep disorders, fibromyalgia, restless legs syndrome, pain associated with spinal cord injury, social phobia, perioperative pain, acute post-surgical pain, opioid use, neuropathic pain, musculoskeletal pain, chronic pain, osteoarthritis pain, muscle pain, migraine, hot flashes, faintness attacks, urinary incontinence, ethanol withdrawal syndrome, and premature ejaculation.

16. The pharmaceutical composition of claim 11 , comprising an agent chosen from an opioid agonist, a selective serotonin re-uptake inhibitor, and a selective noradrenaline re-uptake inhibitor.

17. A mesophasic form of calcium (3S)-{[(1R)-benzoyloxyethoxy]carbonylaminomethyl}-5-methyl-hexanoate, which exhibits characteristic scattering angles (2θ) at least at 5.3°±0.2°, 9.3°±0.2°, 10.50°±0.2° and 13.9°±0.2° in an X-ray powder diffractogram measured using Cu—K α radiation.

18. The mesophasic form of claim 17 , which exhibits a melting point range from 162° C. to 170° C.

19. A pharmaceutical composition comprising the mesophasic form of claim 17 and a pharmaceutically acceptable vehicle.

20. The pharmaceutical composition of claim 19 , comprising a therapeutically effective amount of the mesophasic form for treating a disease or disorder in a patient, wherein the disease or disorder is chosen from post-operative pain, chemotherapy-induced pain, general anxiety disorder, post-herpetic neuralgia, painful diabetic peripheral neuropathy, sleep disorders, fibromyalgia, restless legs syndrome, pain associated with spinal cord injury, social phobia, perioperative pain, acute post-surgical pain, opioid use, neuropathic pain, musculoskeletal pain, chronic pain, osteoarthritis pain, muscle pain, migraine, hot flashes, faintness attacks, urinary incontinence, ethanol withdrawal syndrome, and premature ejaculation.

21. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition is a sustained release oral dosage formulation.

22. A method of treating a disease or disorder in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the pharmaceutical composition of claim 19 , wherein the disease or disorder is chosen from post-operative pain, chemotherapy-induced pain, general anxiety disorder, post-herpetic neuralgia, painful diabetic peripheral neuropathy, sleep disorders, fibromyalgia, restless legs syndrome, pain associated with spinal cord injury, social phobia, perioperative pain, acute post-surgical pain, opioid use, neuropathic pain, musculoskeletal pain, chronic pain, osteoarthritis pain, muscle pain, migraine, hot flashes, faintness attacks, urinary incontinence, ethanol withdrawal syndrome, and premature ejaculation.

23. A kit comprising the pharmaceutical composition of claim 19 and instructions for administering the pharmaceutical composition to a patient in need thereof for treating a disease or disorder chosen from post-operative pain, chemotherapy-induced pain, general anxiety disorder, post-herpetic neuralgia, painful diabetic peripheral neuropathy, sleep disorders, fibromyalgia, restless legs syndrome, pain associated with spinal cord injury, social phobia, perioperative pain, acute post-surgical pain, opioid use, neuropathic pain, musculoskeletal pain, chronic pain, osteoarthritis pain, muscle pain, migraine, hot flashes, faintness attacks, urinary incontinence, ethanol withdrawal syndrome, and premature ejaculation.

24. The pharmaceutical composition of claim 19 , comprising an agent chosen from an opioid agonist, a selective serotonin re-uptake inhibitor, and a selective noradrenaline re-uptake inhibitor.