Methods of treating lower urinary tract disorders using sodium channell modulators

• US 20040209960A1
• Filed: 01/30/2004
• Published: 10/21/2004
• Est. Priority Date: 01/30/2003
• Status: Abandoned Application

• Current Assignee: Dynogen Pharmaceuticals, Inc. (Edusa Pharmaceuticals, Inc.)
• Original Assignee: Dynogen Pharmaceuticals, Inc. (Edusa Pharmaceuticals, Inc.)
• Inventors: Thor, Karl Bruce, Fraser, Matthew Oliver, Burgard, Edward C.
• Application Number:
  US10/769,072
• Publication Number:
  US 20040209960A1
• Time in Patent Office: Days
• US Class Current: 514/649
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/357 having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/37 Coumarins, e.g. psoralen
• CPC Class Codes: A61K 31/38 having sulfur as a ring hetero atom
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder

Abstract

The invention relates to methods of using sodium channel modulators, particularly TTX-R sodium channel modulators and/or activity dependent sodium channel modulators to treat painful and non-painful lower urinary tract disorders, particularly painful and non-painful overactive bladder with and/or without loss of urine.

Claims

1. A method for treating a lower urinary tract disorder, which comprises administering to an individual in need thereof a therapeutically effective amount of an active agent wherein said agent is a sodium channel modulator or a pharmaceutically acceptable salt, ester, amide, prodrug, active metabolite or derivative thereof, and wherein said sodium channel modulator is not tolperisone or vinpocetine, and wherein said sodium channel modulator is not a semicarbazone or thiosemicarbazone when said lower urinary tract disorder is OAB Wet.

2. The method of claim 1, wherein the lower urinary tract disorder is selected from the group consisting of overactive bladder, prostatitis, prostadynia, interstitial cystitis, benign prostatic hyperplasia, and spastic bladder.

3. The method of claim 1, wherein the active agent is contained within a pharmaceutical formulation.

4. The method of claim 3, wherein the pharmaceutical formulation is a unit dosage formulation.

5. The method of claim 1, wherein the active agent is administered on an as-needed basis.

6. The method of claim 1, wherein the active agent is administered prior to commencement of an activity wherein suppression of the symptoms of a lower urinary tract disorder would be desirable.

7. The method of claim 6, wherein the active agent is administered from about 0 to about 3 hours prior to commencement of an activity wherein suppression of said symptoms would be desirable.

8. The method of claim 3, wherein the formulation is a controlled release dosage formulation.

9. The method of claim 8, wherein the formulation is a delayed release dosage formulation.

10. The method of claim 8, wherein the formulation is a sustained release dosage formulation.

11. The method of claim 9, wherein the formulation is a sustained release dosage formulation.

12. The method of claim 10, wherein the sustained release dosage formulation provides drug release over a time period of from about 6 hours to about 8 hours.

13. The method of claim 1, wherein the active agent is administered orally.

14. The method of claim 3, wherein the active agent is administered orally.

15. The method of claim 14, wherein the pharmaceutical formulation is selected from the group consisting of tablets, capsules, caplets, solutions, suspensions, syrups, granules, beads, powders and pellets.

16. The method of claim 1, wherein the active agent is administered transmucosally.

17. The method of claim 16, wherein the active agent is administered sublingually.

18. The method of claim 16, wherein the active agent is administered buccally.

19. The method of claim 16, wherein the active agent is administered intranasally.

20. The method of claim 16, wherein the active agent is administered transurethrally.

21. The method of claim 16, wherein the active agent is administered rectally.

22. The method of claim 16, wherein the active agent is administered by inhalation.

23. The method of claim 1, wherein the active agent is administered topically.

24. The method of claim 1, wherein the active agent is administered transdermally.

25. The method of claim 1, wherein the active agent is administered parenterally.

26. The method of claim 1, wherein the active agent is administered intrathecally.

27. The method of claim 1, wherein the lower urinary tract disorder is a painful lower urinary tract disorder.

28. The method of claim 1, wherein the lower urinary tract disorder is a non-painful lower urinary tract disorder.

29. The method of claim 28, wherein the non-painful lower urinary tract disorder is non-painful overactive bladder.

30. The method of claim 1, wherein the lower urinary tract disorder is selected from the group consisting of overactive bladder, prostatitis, prostadynia, interstitial cystitis, benign prostatic hyperplasia, and spastic bladder.

31. The method of claim 1, wherein said sodium channel modulator is:

a. a TTX-R sodium channel modulator, or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof;

or

b. an activity-dependent sodium channel modulator, or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.

32. The method of claim 31, wherein said TTX-R sodium channel modulator is:

a. a compound that interacts with Na_v1.8 channels, or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof;

or

b. a compound that interacts with Na_v.1.9 channels, or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.

33. The method of claim 1, wherein said sodium channel modulator is Ralfinamide or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.

34. The method of claim 1, wherein said sodium channel modulator is Ambroxol or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.

35. The method of claim 1, wherein said sodium channel modulator is Carbamazepine or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.

36. The method of claim 1, wherein said sodium channel modulator is Topiramate or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.

37. The method of claim 1, wherein said sodium channel modulator is Sipatrigine or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.

38. The method of claim 1, wherein said sodium channel modulator is Losigamone or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.

39. The method of claim 1, wherein said sodium channel modulator is Mexiletine or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.

40. The method of claim 1, wherein said sodium channel modulator is Lamotrigine or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof.

41. The method of claim 2, wherein the pharmaceutical formulation further comprises an additional active agent.

42. The method of claim 41, wherein the additional active agent is selected from the group consisting of:

an antispasmodic, a tricyclic antidepressant, duloxetine, venlafaxine, a monoamine reuptake inhibitor, a spasmolytic, an anticholinergic, gabapentin, pregabalin, a substituted aminomethyl-phenyl-cyclohexane derivative, a 5-HT₃ antagonist, a 5-HT₄ antagonist, a β

3 adrenergic agonist, a neurokinin receptor antagonist, a bradykinin receptor antagonist, a nitric oxide donor, and derivatives thereof.

43. A method for treating overactive bladder, which comprises administering to an individual in need thereof a therapeutically effective amount of an active agent wherein said agent is a sodium channel modulator or a salt, enantiomer, analog, ester, amide, prodrug, active metabolite, and derivative thereof, and wherein said sodium channel modulator is not tolperisone or vinpocetine, and wherein said sodium channel modulator is not a and wherein said sodium channel modulator is not tolperisone or vinpocetine, and wherein said sodium channel modulator is not a semicarbazone or thiosemicarbazone when said lower urinary tract disorder is OAB Wet.

44. A pharmaceutical formulation for treating overactive bladder and adapted for transmucosal drug administration, comprising a therapeutically effective amount of a sodium channel modulator, or a pharmaceutically acceptable salt, ester, amide, prodrug, or active metabolite thereof, and a carrier suitable for transmucosal drug delivery buccally, sublingually, intranasally, rectally, or by inhalation, and wherein said sodium channel modulator is not tolperisone or vinpocetine, and wherein said sodium channel modulator is not a semicarbazone or thiosemicarbazone when said lower urinary tract disorder is OAB Wet.

45. A packaged kit for a patient to use in the treatment of overactive bladder, comprising:

a pharmaceutical formulation of a sodium channel modulator;

a container housing the pharmaceutical formulation during storage and prior to administration; and

instructions for carrying out drug administration in a manner effective to treat overactive bladder, and wherein said sodium channel modulator is not tolperisone or vinpocetine, and wherein said sodium channel modulator is not a semicarbazone or thiosemicarbazone when said lower urinary tract disorder is OAB Wet.