VAGINALLY ADMINISTERED ANTI-DYSRHYTHMIC AGENTS FOR TREATING PELVIC PAIN

• US 20080182841A1
• Filed: 09/04/2007
• Published: 07/31/2008
• Est. Priority Date: 10/29/2001
• Status: Abandoned Application

• Current Assignee: Juniper Pharmaceuticals, Inc. (Catalent, Inc.)
• Original Assignee: Juniper Pharmaceuticals, Inc. (Catalent, Inc.)
• Inventors: De Zeigler, Dominique, Levine, Howard L., Bologna, William J.
• Application Number:
  US11/849,862
• Publication Number:
  US 20080182841A1
• Time in Patent Office: Days
• US Class Current: 514/211.07
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/245 Amino benzoic acid types, e.g. procaine, novocaine salicylic acid esters A61K31/60
• CPC Class Codes: A61K 31/554 having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The invention relates to a pharmaceutical composition for relieving pelvic pain or infertility associated with uterine dysrhythmia. The composition includes a locally-administered anti-dysrhythmic treating agent and a bioadhesive extended-release carrier. The composition may be delivered in an extended release formulation that includes a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer, such as polycarbophil. The treating agent may be a local anesthetic, such as lidocaine. The invention also relates to a method of treating or preventing pelvic pain, or treating or improving infertility, by inserting a mixture of an anti-dysrhythmic treating agent and a bioadhesive carrier into the vagina of the patient to be treated.

Claims

1. A method of treating or preventing pelvic pain, or for treating or improving infertility, associated with uterine dysrhythmia comprising vaginally administering, to a patient in need thereof, a composition that comprises a therapeutically effective amount of an anti-dysrhythmic treating agent which normalizes abnormal uterine contractions and a pharmaceutically acceptable bioadhesive carrier that releases the treating agent over an extended period of time after administration.

2. The method of claim 1, wherein the anti-dysrhythmic treating agent comprises one or more agents selected from the group consisting of coronary anti-arrhythmic, local anesthetics, calcium channel blocker, autocoid agents, prostaglandin blockers, non-steroidal anti-inflammatory drugs, COX inhibitors, thromboxane synthase inhibitors, and leukotriene inhibitors.

3. The method of claim 1, wherein the treating agent is lidocaine at a concentration of about 2% to 10% by weight.

4. The method of claim 1, wherein the composition is prepared so that a single dosage of about 1 to 1.5 g of the composition will release about 20 to 150 mg of lidocaine over at least about 24 hours after administration.

5. The method of claim 1, wherein the treating agent is delivered and released over at least 24 hours.

6. The method of claim 5, wherein the treating agent is delivered and released over at least 48 hours.

7. The method of claim 6, wherein the treating agent is delivered and released over at least 72 hours.

8. The method of claim 5, wherein the carrier comprises a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer.

9. The method of claim 8, wherein the carrier comprises polycarbophil and the treating agent comprises lidocaine.

10. The method of claim 8, wherein the treating agent is lidocaine and the lidocaine is administered in a dosage that releases about 20 to 100 mg of lidocaine over at least about 48 hours.

11. The method of claim 10, wherein the composition is administered about every 2 to 3 days to treat or prevent pelvic pain.

12. The method of claim 1, wherein the treating agent is a local anesthetic and the carrier comprises a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer.

13. The method of claim 12, wherein the treating agent is lidocaine and the carrier comprises polycarbophil.

14. The method of claim 8, wherein the treating agent comprises one or more agents selected from the group consisting of cocaine, chloroprocaine, tetracaine, prilocaine, mepivacaine, buipivacaine, levobupivacaine, articaine, ropivacaine, phenol, benzocaine, pramoxine, dyclonine, etidocaine, procaine, proparacaine, dibucaine, pramoxine, lidocaine, phenytoin, mexiletine, tocainide, procainamide, quinidine, disopyramide, moricizine, propafenone, flecainide, sotalol, bretyllium, amiodarone, verapamil, diltiazem, digoxin, digitoxin, adenosine, propranolol, esmolol, N-acetyl procainamide, amlodipine, bepridil, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, verapamil, pirmagrel, dazoxiben, zileuton, diclofenac, etodolac, fenoprofen, lurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meclofenamate, fenamic acid, meloxicam, nabumetone, naproxin, oxaprozin, piroxicam, sulindac, tolmetin, aspirin, celecoxib, rofecoxib, and valdecoxib.

15. The method of claim 1, wherein the treating agent is selected from the group consisting of coronary anti-arrhythmic, local anesthetics, calcium channel blocker, autocoid agents, prostaglandin blockers, non-steroidal anti-inflammatory drugs, COX inhibitors, thromboxane synthase inhibitors, and leukotriene inhibitors.

16. The method of claim 11, wherein the carrier comprises a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer, and the one or more treating agents are selected from the group consisting of local anesthetics, NSAIDS, and calcium channel blockers.

17. A method of treating or preventing pelvic pain, or for treating or improving infertility, comprising vaginally administering, to a patient in need thereof, a composition that comprises a therapeutically effective amount of an anti-dysrhythmic treating agent which normalizes abnormal uterine contractions and a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer that releases the treating agent over an extended period of time after administration, wherein the pelvic pain or infertility is associated with uterine dysrhythmia.

18. The method of claim 17, wherein the treating agent comprises a local anesthetic.

19. The method of claim 17, wherein the treating agent comprises one or more of coronary anti-arrhythmic, local anesthetics, calcium channel blocker, autocoid agents, prostaglandin blockers, non-steroidal anti-inflammatory drugs, COX inhibitors, thromboxane synthase inhibitors, and leukotriene inhibitors.

20. A method of reducing or relieving uterine dysrhythmia comprising vaginally administering, to a patient in need thereof, a composition that comprises a therapeutically effective amount of an anti-dysrhythmic treating agent which normalizes abnormal uterine contractions and a pharmaceutically acceptable bioadhesive carrier that releases the treating agent over an extended period of time after administration.

21. The method of claim 20, wherein the carrier comprises a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer.

22. The method of claim 20, wherein the treating agent comprises one or more agents selected from the group consisting of cocaine, chloroprocaine, tetracaine, prilocaine, mepivacaine, buipivacaine, levobupivacaine, articaine, ropivacaine, phenol, benzocaine, pramoxine, dyclonine, etidocaine, procaine, proparacaine, dibucaine, pramoxine, lidocaine, phenytoin, mexiletine, tocainide, procainamide, quinidine, disopyramide, moricizine, propafenone, flecainide, sotalol, bretyllium, amiodarone, verapamil, diltiazem, digoxin, digitoxin, adenosine, propranolol, esmolol, N-acetyl procainamide, amlodipine, bepridil, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, verapamil, pirmagrel, dazoxiben, zileuton, diclofenac, etodolac, fenoprofen, lurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meclofenamate, fenamic acid, meloxicam, nabumetone, naproxin, oxaprozin, piroxicam, sulindac, tolmetin, aspirin, celecoxib, rofecoxib, and valdecoxib.

23. The method of claim 20, wherein the treating agent comprises lidocaine.

24. A method for treating or improving infertility, associated with uterine dysrhythmia comprising vaginally administering, to a patient in need thereof, a composition that comprises a therapeutically effective amount of an anti-dysrhythmic treating agent which normalizes abnormal uterine contractions and a pharmaceutically acceptable bioadhesive carrier that releases the treating agent over an extended period of time after administration.

25. The method of claim 24, wherein the carrier comprises a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer.

26. A method of treating or preventing pelvic pain, or for treating or improving infertility, comprising vaginally administering, to a patient in need thereof, a composition that comprises a therapeutically effective amount of an anti-dysrhythmic treating agent which normalizes abnormal uterine contractions and a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer that releases the treating agent over an extended period of time after administration, wherein the pelvic pain or infertility is associated with uterine dysrhythmia and further wherein the treatment is administered two to three days prior to anticipated onset of symptoms.

27. The method of claim 26 wherein the polymer is carbophil.

28. A pharmaceutical vaginal composition for treating or preventing pelvic pain, or for treating or improving infertility, associated with uterine dysrhythmia comprising a therapeutically effective amount of an anti-dysrhythmic treating agent and a pharmaceutically acceptable extended-release bioadhesive carrier.

29. The composition of claim 28, wherein the carrier comprises a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer.

30. The composition of claim 29, wherein the polymer comprises polycarbophil.

31. The composition of claim 29, wherein the anti-dysrhythmic treating agent comprises one or more agents selected from the group consisting of coronary anti-arrhythmic, local anesthetics, calcium channel blocker, autocoid agents, prostaglandin blockers, non-steroidal anti-inflammatory drugs, COX inhibitors, thromboxane synthase inhibitors, and leukotriene inhibitors.

32. The composition of claim 30, wherein the anti-dysrhythmic treating agent comprises one or more agents selected from the group consisting of cocaine, chloroprocaine, tetracaine, prilocaine, mepivacaine, buipivacaine, levobupivacaine, articaine, ropivacaine, phenol, benzocaine, pramoxine, dyclonine, etidocaine, procaine, proparacaine, dibucaine, pramoxine, lidocaine, phenytoin, mexiletine, tocainide, procainamide, quinidine, disopyramide, moricizine, propafenone, flecainide, sotalol, bretyllium, amiodarone, verapamil, diltiazem, digoxin, digitoxin, adenosine, propranolol, esmolol, N-acetyl procainamide, amlodipine, bepridil, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, verapamil, pirmagrel, dazoxiben, zileuton, diclofenac, etodolac, fenoprofen, lurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meclofenamate, fenamic acid, meloxicam, nabumetone, naproxin, oxaprozin, piroxicam, sulindac, tolmetin, aspirin, celecoxib, rofecoxib, and valdecoxib.

33. The composition of claim 29, wherein the treating agent comprises lidocaine.

34. The composition of claim 32, wherein the treating agent is lidocaine at a concentration of about 2% to 10% by weight.

35. The composition of claim 32, wherein the composition is prepared so that a single dosage of about 1 to 1.5 g of the composition will release about 20 to 150 mg of lidocaine over at least about 24 hours after administration.

38. The composition of claim 35, wherein the composition is prepared so that a single dosage will release the treating agent over at least about 48 to 72 hours.

39. A pharmaceutical vaginal composition for treating or preventing pelvic pain, or for treating or improving infertility, associated with uterine dysrhythmia comprising a therapeutically effective amount of a local anesthetic treating agent and a pharmaceutically acceptable extended-release bioadhesive carrier.

40. The composition of claim 39, wherein the carrier includes a bioadhesive, water-swellable, water-insoluble, cross-linked polycarboxylic acid polymer.

41. The composition of claim 40, wherein the treating agent is lidocaine.

42. The composition of claim 41, wherein the polymer is polycarbophil.