Methods of treating lower urinary tract disorders using losigamone

• US 20050107353A1
• Filed: 10/14/2004
• Published: 05/19/2005
• 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:
  US10/965,304
• Publication Number:
  US 20050107353A1
• Time in Patent Office: Days
• US Class Current: 514/200
• 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, preferably Losigamone or a pharmaceutically acceptable salt, enantiomer, analog, ester, amide, prodrug, metabolite, or derivative thereof, 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 symptom of a lower urinary tract disorder, which comprises administering to an individual in need thereof a therapeutically effective amount of Losigamone or a pharmaceutically acceptable salt, enantiomer, analog, ester, amide, prodrug, metabolite, or derivative thereof.

2. The method of claim 1, wherein the Losigamone is (+)-Losigamone.

3. The method of claim 1, wherein the symptom of a lower urinary tract disorder is selected from the group consisting of urinary urgency, incontinence, urge incontinence, stress incontinence, urinary frequency, nocturia, irritative voiding, suprapubic pain related to and relieved by voiding, pelvic pain related to and relieved by voiding, reduced urinary force, and reduced urinary speed of flow.

4. 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.

5. The method of claim 4, wherein the lower urinary tract disorder is overactive bladder.

6. The method of claim 5, wherein the symptom of the lower urinary tract disorder is selected from the group consisting of urinary urgency, incontinence, urge incontinence, stress incontinence, urinary frequency, and nocturia.

7. The method of claim 5, wherein the lower urinary tract disorder is OAB Wet.

8. The method of claim 5, wherein the lower urinary tract disorder is OAB Dry.

9. The method of claim 4, wherein the lower urinary tract disorder is interstitial cystitis.

10. The method of claim 9, wherein the symptom of the lower urinary tract disorder is selected from the group consisting of urinary urgency, urinary frequency, nocturia, irritative voiding, suprapubic pain related to and relieved by voiding, and pelvic pain related to and relieved by voiding.

11. The method of claim 4, wherein the lower urinary tract disorder is benign prostatic hyperplasia.

12. The method of claim 11, wherein the symptom of a lower urinary tract disorder is selected from the group consisting of urinary frequency, urge incontinence, nocturia, and reduced urinary speed of flow.

13. The method of claim 1, wherein the Losigamone or pharmaceutically acceptable salt, enantiomer, analog, ester, amide, prodrug, metabolite, or derivative thereof is administered orally, transmucosally, sublingually, buccally, intranasally, transurethrally, rectally, by inhalation, topically, transdermally, parenterally, or intrathecally.

14. The method of claim 1, wherein the Losigamone or pharmaceutically acceptable salt, enantiomer, analog, ester, amide, prodrug, metabolite, or derivative thereof is administered concurrently with an additional active agent.

15. The method of claim 14, 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.

16. A pharmaceutical formulation for treating a symptom of a lower urinary tract disorder comprising a therapeutically effective amount of Losigamone or a pharmaceutically acceptable salt, enantiomer, analog, ester, amide, prodrug, metabolite, or derivative thereof.

17. The pharmaceutical formulation of claim 16, wherein the Losigamone is (+)-Losigamone.

18. The pharmaceutical formulation of claim 16, wherein the formulation is a controlled release dosage formulation.

19. The pharmaceutical formulation of claim 18, wherein the formulation is a delayed release dosage formulation.

20. The pharmaceutical formulation of claim 18, wherein the formulation is a sustained release dosage formulation.

21. The pharmaceutical formulation of claim 20, wherein the sustained release dosage formulation provides drug release over a time period of from about 6 hours to about 24 hours.

22. The pharmaceutical formulation of claim 16, wherein the pharmaceutical formulation is selected from the group consisting of tablets, capsules, caplets, solutions, suspensions, syrups, granules, beads, powders, and pellets.

23. The pharmaceutical formulation of claim 16, wherein the pharmaceutical formulation is formulated for oral, transmucosal, sublingual, buccal, intranasal, inhalation, transurethral, rectal, topical, transdermal, parenteral, intrathecal, vaginal, or perivaginal administration.