CA2608486A1 - Cyclooxygenase inhibitor and calcium channel antagonist compositions and methods for use in urological procedures - Google Patents

Cyclooxygenase inhibitor and calcium channel antagonist compositions and methods for use in urological procedures Download PDF

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CA2608486A1
CA2608486A1 CA002608486A CA2608486A CA2608486A1 CA 2608486 A1 CA2608486 A1 CA 2608486A1 CA 002608486 A CA002608486 A CA 002608486A CA 2608486 A CA2608486 A CA 2608486A CA 2608486 A1 CA2608486 A1 CA 2608486A1
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composition
spasm
inflammation
urinary tract
calcium channel
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CA2608486C (en
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Gregory A. Demopulos
Jeffrey M. Herz
Wayne R. Gombotz
Hui-Rong Shen
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Omeros Corp
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/06—Anti-spasmodics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/402—Anaestetics, analgesics, e.g. lidocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/432—Inhibitors, antagonists

Abstract

Compositions of a cyclooxygenase inhibitor and a calcium channel antagonist in a liquid carrier. The composition may be administered the the urinary tract during urological diagnostic, interventional, surgical and other medical procedures. One disclosed composition comprises ketoprofen and nifedipine in a liquid irrigation carrier, and includes a solubilizing agent, stabilizing agents and a buffering agent.

Claims (90)

1. A locally deliverable composition for inhibiting pain/inflammation and spasm, comprising a combination of ketoprofen and a calcium channel antagonist in a carrier, each of the ketoprofen and the calcium channel antagonist included in a therapeutically effective amount such that the combination inhibits pain/inflammation and spasm at a site of local delivery.
2. The composition of Claim 1, wherein the calcium channel antagonist comprises an L-type calcium channel antagonist.
3. The method of Claim 2, wherein the L-type calcium channel antagonist is selected from the group consisting of verapamil, diltiazem, bepridil, mibefradil, nifedipine, nicardipine, isradipine, amlodipine, felodipine, nisoldipine and nimodipine.
4. The method of Claim 2, wherein the L-type calcium channel antagonist comprises a dihydropyridine.
5. The composition of Claim 4, wherein the L-type calcium channel antagonist is selected from the group consisting of nifedipine, nicardipine, isradipine, amlodipine, felodipine, nisoldipine and nimodipine.
6. The method of Claim 5, wherein the L-type calcium channel antagonist comprises nifedipine.
7. The composition of Claim 5, wherein the L-type calcium channel antagonist has an onset of action of less than or equal to 10 minutes.
8. The composition of Claim 1, wherein the calcium channel antagonist comprises nifedipine.
9. The composition of Claim 8, wherein ketoprofen and nifedipine are included in the composition in a ketoprofen:nifedipine molar ratio of from
10:1 to 1:10.~~~

10. The composition of Claim 9, wherein ketoprofen and nifedipine are included in the composition in a ketoprofen:nifedipine molar ratio of from 4:1 to 1:1.
11. The composition of Claim 10, wherein ketoprofen and nifedipine are included in the composition in a ketoprofen:nifedipine molar ratio of 3:1.
12. The composition of Claim 8, wherein ketoprofen is included in the compositon at a concentration of no more than 500,000 nanomolar and nifedipine is included in the composition at a concentration of no more than 200,000 nanomolar.
13. The composition of Claim 12, wherein ketoprofen is included in the compositon at a concentration of no more than 300,000 nanomolar and nifedipine is included in the composition at a concentration of no more than 100,000 nanomolar.
14. The composition of Claim 13, wherein ketoprofen is included in the compositon at a concentration of no more than 50,000 nanomolar and nifedipine is included in the composition at a concentration of no more than 25,000 nanomolar.
15. The composition of Claim 8, wherein the carrier comprises an aqueous carrier.
16. The composition of Claim 15, wherein the composition comprises at least one stabilizing agent.
17. The composition of Claim 16, wherein the at least one stabilizing agent comprises propyl gallate.
18. The composition of Claim 17, wherein the composition further comprises sodium metabisulfite.
19. The composition of Claim 18, wherein the composition further comprises polyethylene glycol 400 as a cosolvent.
20. The composition of Claim 19, wherein the composition further comprises a citric acid buffer.
21. The composition of Claim 18, wherein the composition further comprises a buffer.
22. The composition of Claim 18, wherein the buffer comprises a citric acid buffer.
23. The composition of Claim 15, wherein the composition further comprises a cosolvent.
24. The composition of Claim 23, wherein the cosolvent comprises polyethylene glycol.
25. The composition of Claim 24, wherein the cosolvent comprises polyethylene glycol 400.
26. The composition of Claim 23, wherein the composition further comprises propyl gallate.
27. The composition of Claim 8, wherein the composition further comprises at least one stabilizing agent.
28. The composition of Claim 27, wherein the stabilizing agent comprises propyl gallate.
29. The composition of Claim 28, wherein the composition further comprises sodium metabilsulfite.
30. The composition of Claim 1, wherein ketoprofen is included in the compositon at a concentration of no more than 500,000 nanomolar and the calcium channel antagonist is included in the composition at a concentration of no more than 200,000 nanomolar.
31. The composition of Claim 30, wherein ketoprofen is included in the compositon at a concentration of no more than 300,000 nanomolar and the calcium channel antagonist is included in the composition at a concentration of no more than 100,000 nanomolar.
32. The composition of Claim 31, wherein ketoprofen is included in the compositon at a concentration of no more than 50,000 nanomolar and the calcium channel antagonist is included in the composition at a concentration of no more than 25,000 nanomolar.
33. The composition of Claim 1, wherein ketoprofen comprises the S-(+)-enantiomer, dexketoprofen.
34. The composition of Claim 1, wherein the carrier comprises an aqueous carrier.
35. The composition of Claim 34, wherein the composition comprises at least one stabilizing agent.
36. The composition of Claim 35, wherein the at least one stabilizing agent comprises propyl gallate.
37. The composition of Claim 36, wherein the composition further comprises sodium metabisulfite.
38. The composition of Claim 37, wherein the composition further comprises polyethylene glycol 400 as a cosolvent.
39. The composition of Claim 38, wherein the composition further comprises a citric acid buffer.
40. The composition of Claim 37, wherein the composition further comprises a buffer.
41. The composition of Claim 40, wherein the buffer comprises a citric acid buffer.
42. The composition of Claim 34, wherein the composition further comprises a cosolvent.
43. The composition of Claim 42, wherein the cosolvent comprises polyethylene glycol.
44. The composition of Claim 43, wherein the cosolvent comprises polyethylene glycol 400.
45. The composition of Claim 42, wherein the composition further comprises propyl gallate.
46. The composition of Claim 1, wherein the carrier comprises a liquid irrigation carrier.
47. The composition of Claim 1, wherein the composition is coated onto an implantable device or medical instrument.
48. The composition of Claim 1, wherein the composition is impregnated into an implantable device or medical instrument.
49. A locally deliverable composition for inhibiting pain/inflammation and spasm, comprising a combination of a cyclooygenase inhibitor and a calcium channel antagonist, each included in a therapeutically effective amount such that the combination inhibits pain/inflammation and spasm at a site of local delivery, propyl gallate as a stabilizing agent and a liquid carrier.
50. The composition of Claim 49, wherein the composition comprises polyethylene glycol as a cosolvent.
51. The composition of Claim 50, wherein the composition comprises polyethylene glycol 400.
52. The composition of Claim 49, wherein the composition comprises at least a second stabilizing agent.
53. The composition of Claim 52, wherein the second stabilizing agent comprises sodium metabisulfite.
54. The composition of Claim 53, wherein the composition further comprises a citric acid buffer.
55. The composition of Claim 52, wherein the the composition further comprises a citric acid buffer.
56. A locally deliverable composition for inhibiting pain/inflammation and spasm, comprising a combination of a cyclooxygenase inhibitor and a calcium channel antagonist, each included in a therapeutically effective amount such that the combination inhibits pain/inflammation and spasm at a site of local delivery, an aqueous liquid carrier, a cosolvent, at least one stabilizing agent and a buffer.
57. A method of inhibiting pain/inflammation and spasm in the urinary tract, comprising:

delivering to the urinary tract a composition including a combination of ketoprofen and a calcium channel antagonist in a carrier, each of the ketoprofen and the calcium channel antagonist included in a therapeutically effective amount such that the combination inhibits pain/inflammation and spasm in the urinary tract.
58. The method of Claim 57, wherein the composition is delivered periprocedurally to the urinary tract during a urological diagnostic, interventional, surgical and other medical procedure.
59. The method of Claim 58, wherein the composition is periprocedurally delivered during a cystoscopic procedure.
60. The method of Claim 58, wherein the composition is periprocedurally delivered during a ureteroscopic procedure.
61. The method of Claim 58, wherein the composition is periprocedurally delivered during a procedure to remove, fragment or dislodge a kidney or bladder stone.
62. The method of Claim 58, wherein the composition is periprocedurally delivered during a procedure that causes thermal injury to urinary tract tissue.
63. The method of Claim 62, wherein the composition is periprocedurally delivered during a laser, microwave ablation, radiofrequency ablation, electrocauterization or cryoblation procedure.
64. The method of Claim 58, wherein the composition is periprocedurally delivered during a transurethral resection of a prostate.
65. The method of Claim 58, wherein the composition is periprocedurally delivered transrectally or transperitoneally to the prostate.
66. The method of Claim 57, wherein the calcium channel antagonist in the composition comprises nifedipine.
67. The method of Claim 57, wherein the ketoprofen in the composition comprises comprises the S-(+)-enantiomer, dexketoprofen.
68. A method of inhibiting pain/inflammation and spasm in the urinary tract during a diagnostic, interventional, surgical or other medical urological procedure, comprising:

periprocedurally delivering to the urinary tract during a urological procedure a composition including a combination of ketoprofen and nifedipine in a carrier, each of the ketoprofen and the nifedipine included in a therapeutically effective amount such that the combination inhibits pain/inflammation and spasm in the urinary tract.
69. The method of Claim 68, wherein the composition is during a cystoscopic procedure.
70. The method of Claim 68, wherein the composition is periprocedurally delivered during a ureteroscopic procedure.
71. The method of Claim 68, wherein the composition is periprocedurally delivered during a procedure to remove, fragment or dislodge a kidney or bladder stone.
72. The method of Claim 68, wherein the composition is periprocedurally delivered during a procedure that causes thermal injury to urinary tract tissue.
73. The method of Claim 72, wherein the composition is periprocedurally delivered during a laser, microwave ablation, radiofrequency ablation, electrocauterization or cryoblation procedure.
74. The method of Claim 68, wherein the composition is periprocedurally delivered during a transurethral resection of a prostate.
75. The method of Claim 68, wherein the composition is periprocedurally delivered transrectally or transperitoneally to the prostate.
76. The method of Claim 68, wherein the ketoprofen in the composition comprises comprises the S-(+)-enantiomer, dexketoprofen.
77. A method of inhibiting pain/ inflammation and spasm in the urinary tract during a urological procedure, comprising:

periprocedurally delivering to the urinary tract during a ureteroscopic procedure a composition including a combination of a cyclooxygenase inhibitor and a calcium channel antagonist in a carrier, each of the cyclooxygenase inhibitor and the calcium channel antagonist included in a therapeutically effective amount such that the combination inhibits pain/inflammation and spasm in the urinary tract.
78. The method of Claim 77, wherein the cyclooxygenase (COX) inhibitor in the composition comprises a nonselective COX-1/COX-2 inhibitor.
79. A method of inhibiting pain/inflammation and spasm in the urinary tract during a urological procedure, comprising:

periprocedurally delivering to the urinary tract during a procedure to remove, fragment or dislodge a kidney or bladder stone a composition including a combination of a cyclooxygenase inhibitor and a calcium channel antagonist in a carrier, each of the cyclooxygenase inhibitor and the calcium channel antagonist included in a therapeutically effective amount such that the combination inhibits pain/inflammation and spasm in the urinary tract.
80. The method of Claim 79, wherein the cyclooxygenase (COX) inhibitor in the composition comprises a nonselective COX-1/COX-2 inhibitor.
81. A method of inhibiting pain/inflammation and spasm in the urinary tract during a urological procedure, comprising:

periprocedurally delivering to the urinary tract during a procedure that causes thermal injury to urinary tract tissue a composition including a combination of a cyclooxygenase inhibitor and a calcium channel antagonist in a carrier, each of the cyclooxygenase inhibitor and the calcium channel antagonist included in a therapeutically effective amount such that the combination inhibits pain/inflammation and spasm in the urinary tract.
82. The method of Claim 81, wherein the cyclooxygenase (COX) inhibitor in the composition comprises a nonselective COX-1/COX-2 inhibitor.
83. The method of Claim 81, wherein the composition is delivered periprocedurally to the urologic structure during a laser, microwave ablation, radiofrequency ablation, electrocauterization or cryoblation procedure.
84. A method of inhibiting pain/inflammation and spasm during a urological procedure, comprising:

periprocedurally delivering transrectally or transperitoneally to the prostate a composition including a combination of a cyclooxygenase inhibitor and a calcium channel antagonist in a carrier, each of the cyclooxygenase inhibitor and the calcium channel antagonist included in a therapeutically effective amount such that the combination inhibits pain/inflammation and spasm.
85. The method of Claim 84, wherein the cyclooxygenase (COX) inhibitor in the composition comprises a nonselective COX-1/COX-2 inhibitor.
86. A method of inhibiting pain, inflammation and/or spasm in the urinary tract during a urological procedure, comprising:

periprocedurally delivering to the urinary tract during a ureteroscopic procedure a composition including a combination of a plurality of agents that inhibit pain/inflammation and/or spasm in a carrier, each agent included in a therapeutically effective amount such that the combination inhibits pain/inflammation and/or spasm in the urinary tract.
87. A method of inhibiting pain, inflammation and/or spasm in the urinary tract during a urological procedure, comprising:

periprocedurally delivering to the urinary tract during a procedure to remove, fragment or dislodge a kidney or bladder stone a composition including a combination of a plurality of agents that inhibit pain/inflammation and/or spasm in a carrier, each agent included in a therapeutically effective amount such that the combination inhibits pain/inflammation and/or spasm in the urinary tract.
88. A method of inhibiting pain, inflammation and/or spasm in the urinary tract during a urological procedure, comprising:

periprocedurally delivering to the urinary tract during a procedure that causes thermal injury to urinary tract tissue a composition including a combination of a plurality of agents that inhibit pain/inflammation and/or spasm in a carrier, each agent included in a therapeutically effective amount such that the combination inhibits pain/inflammation and/or spasm in the urinary tract.
89. The method of Claim 88, wherein the composition is delivered periprocedurally to the urologic structure during a laser, microwave ablation, radiofrequency ablation, electrocauterization or cryoblation procedure.
90. A method of inhibiting pain, inflammation and/or spasm during a urological procedure, comprising:

periprocedurally delivering transrectally or transperitoneally to the prostate a composition including a combination of a plurality of agents that inhibit pain/inflammation and/or spasm in a carrier, each agent included in a therapeutically effective amount such that the combination inhibits pain/inflammation and/or spasm.
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US68348805P 2005-05-20 2005-05-20
US60/683,488 2005-05-20
PCT/US2006/009771 WO2006127096A2 (en) 2005-05-20 2006-03-17 Cyclooxygenase inhibitor and calcium channel antagonist compositions and methods for use in urological procedures

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EP (1) EP1881821B1 (en)
JP (1) JP5008206B2 (en)
KR (3) KR20080014056A (en)
CN (1) CN101180040B (en)
AU (2) AU2006249684A1 (en)
CA (1) CA2608486C (en)
ES (1) ES2614474T3 (en)
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WO (1) WO2006127096A2 (en)

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