Composition And Its Use For The Manufacture Of A Medicament For Treating, Prophylactically Treating, Preventing Cancer And/Or Infections In The Urinary Tract

• US 20090098187A1
• Filed: 11/15/2006
• Published: 04/16/2009
• Est. Priority Date: 11/14/2005
• Status: Abandoned Application

• Current Assignee: Nolabs AB
• Original Assignee: Nolabs AB
• Inventors: Wiklund, Peter, Peters, Tor
• Application Number:
  US12/093,572
• Publication Number:
  US 20090098187A1
• Time in Patent Office: Days
• US Class Current: 424/425
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A composition is provided that allows for treatment of cancer, prophylactic treatment, and treatment of infection in the urinary tract. The composition comprises a nitric oxide (NO) eluting polymer that elutes nitric oxide (NO) in a therapeutic dose. The nitric oxide (NO) eluting polymer may be integrated with a carrier material, such that said carrier material, in use, regulates and controls the elution of said therapeutic dosage of nitric oxide (NO). The nitric oxide (NO) eluting polymer may be provided as a Solution or Suspension. Furthermore, a manufacturing method for said composition is disclosed, as well as uses of said composition in the urinary tract.

Claims

1. Nitric oxide (NO) for use as a medicament in the treatment of cancer in the urinary tract.

2. Nitric oxide (NO) for use as a medicament in the treatment of cancer in the epithelial cells in the urinary tract.

3. Nitric oxide (NO) for use as a medicament in the treatment of infection in the urinary tract.

4. Use of a nitric oxide (NO) eluting polymer for the manufacture of a composition for the treatment and/or prevention of cancer and/or infection in the urinary tract wherein nitric oxide is loaded to said composition so that said composition elutes nitric oxide (NO) from said eluting polymer in a therapeutic dose when used.

5. Use according to claim 4, wherein said composition is a composition configured to therapeutically target treat, prophylactically treat and/or prevent cancer and/or infection in a urinary tract, wherein

said composition is configured to elute nitric oxide (NO) in a therapeutic dosage, and wherein said composition is configured to expose the urinary tract to said eluted nitric oxide,

and wherein said composition comprises a nitric oxide (NO) eluting polymer configured to elute a therapeutic dosage of nitric oxide (NO) to expose an area of treatment in the urinary tract to said nitric oxide when said polymer in use elutes nitric oxide (NO), and

wherein elution of said therapeutic dosage of nitric oxide (NO) from said nitric oxide (NO) eluting polymer is regulateable.

6. Use according to claim 4 or 5, wherein said therapeutic dose is in the range of 0.001 to 5000 ppm, such as 0.01 to 3000 ppm, such as 0.1 to 1000 ppm, such as 1 to 100 ppm, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 ppm.

7. A medical device comprising a composition, wherein the medical device is a urinary catheter comprising a balloon, characterized by

said balloon having a permeable wall, wherein said composition is

a composition configured to therapeutically target treat, prophylactically treat and/or prevent cancer and/or infection in a urinary tract, wherein

said composition is configured to elute nitric oxide (NO) in a therapeutic dosage, and wherein said composition is configured to expose the urinary tract to said eluted nitric oxide, and wherein

said composition comprises a nitric oxide (NO) eluting polymer configured to elute a therapeutic dosage of nitric oxide (NO) to expose an area of treatment in the urinary tract to said nitric oxide when said polymer in use elutes nitric oxide (NO), and

wherein elution of said therapeutic dosage of nitric oxide (NO) from said nitric oxide (NO) eluting polymer is regulateable, and wherein

said wall is permeable for said nitric oxide (NO) such that said nitric oxide (NO) upon application of said urinary catheter is eluted, from inside of the catheter balloon and from said composition to said urinary tract through said wall.

8. Medical device according to claim 7, wherein said wall is of silicone.

9. Medical device according to claim 7 or 8, wherein said regulateable elution of nitric oxide (NO) comprises prolonged, delayed, spontaneous, instantaneous or immediate, elution of nitric oxide from said nitric oxide (NO) eluting polymer.

10. Medical device according to any of claims 7 to 9, wherein said elution of said therapeutic dosage of nitric oxide (NO) from said nitric oxide (NO) eluting polymer is regulateable by means of a carrier material.

11. Medical device according to claim 10, wherein said nitric oxide (NO) eluting polymer is integrated with a carrier material, such that said carrier material, in use, regulates and controls the elution of said therapeutic dosage of nitric oxide (NO).

12. Medical device according to any of claims 7 to 9, wherein said nitric oxide (NO) eluting polymer comprises diazeniumdiolate groups, S-nitrosylated groups, and O-nitrosylated groups, or any combination of these.

13. Medical device according to any of claims 7 to 9, or 12, wherein said nitric oxide (NO) eluting polymer is L-PEI (linear polyethyleneimine), loaded with nitric oxide (NO) through said diazeniumdiolate groups, S-nitrosylated groups, or O-nitrosylated groups, or any combination these, arranged for release of said nitric oxide (NO) to an adjacent mammal tissue in said urinary tract.

14. Medical device according to any of claims 7 to 9, wherein said nitric oxide eluting polymer is selected from the group comprising amino cellulose, amino dextrans, chitosan, aminated chitosan, polyethyleneimine, PEI-cellulose, polypropyleneimine, polybutyleneimine, polyurethane, poly(buthanediol spermate), poly(iminocarbonate), polypeptide, Carboxy Methyl Cellulose (CMC), polystyrene, poly(vinyl chloride), and polydimethylsiloxane, or any combinations of these, and these mentioned polymers grafted to an inert backbone, such as a polysaccharide backbone or cellulosic backbone.

15. Medical device according to any of claims 7 to 9, wherein said nitric oxide eluting polymer comprises a secondary amine in the backbone or a secondary amine as a pendant.

16. Medical device according to claim 15, wherein a positive ligand is located on the neighbor carbon atom to the secondary amine.

17. Medical device according to any of claims 7 to 9, wherein said elution of said therapeutic dosage of nitric oxide (NO) from said nitric oxide (NO) eluting polymer is regulateable by means of a cation.

18. Medical device according to any of claims 7 to 9 or claim 17, wherein said composition comprises a cation, said cation stabilizing the nitric oxide eluting polymer.

19. Medical device according to claim 18, wherein said cation is selected from the group comprising Na+, K+, Li+, Be2+, Ca2+, Mg2+, Ba2+, and/or Sr2+, or any combinations thereof.

20. Medical device according to any of claims 7 to 19, wherein said polymer is L-PEI (linear polyethyleneimine), loaded with nitric oxide (NO), arranged for release of the nitric oxide (NO) at said urinary tract.

21. Medical device according to any of claims 7 to 20, wherein said composition comprises an antioxidant.

22. Medical device according to claim 21, wherein said antioxidant is ascorbic acid.

23. Medical device according to any of claims 7 to 22, wherein said composition comprises a pH lowering substance.

24. Medical device according to claim 23, wherein said pH lowering substance is chosen from the group consisting of ammonium chloride, ammonium sulphate, a biologically acceptable acid, or a combination of these.

25. Medical device according to any of claims 7 to 24, further comprising a pH-adjusting agent, for lowering the pH value in the urinary tract.

26. Medical device according to claim 25, wherein said pH-adjusting agent is chosen from the group consisting of ammonium chloride, ammonium sulphate, a biological acceptable acid, or a combination of several pH-adjusting agents.

27. Medical device according to any of claims 7 to 26, wherein said composition comprises nitric oxide (NO) eluting ethambutol.

28. Medical device according to any of claims 7 to 27, wherein said composition is in a form selected from the group consisting of powder, nano-particles or micro-spheres, pill, tablet, pellet, gel, hydrogel, foam, cream, granules, capsule, solution, and suspension, or combinations thereof.

29. Medical device according to claim 28, wherein said nano-particles, micro-spheres, granules, or powder, are encapsulated, combined with, or integrated, in a material, selected from the group consisting of polyvinylacetates, polylacticacids, starch, cellulose, polyhydroxyalkanoates, polyesters, polycaprolactone, polyvinylalcohol, protein based plastics, and/or gelatine, polyesters, polyamides, polyethers, polyurethanes, polycarbonates, polyvinylacetates, polylacticacids, starch, cellulose, polyhydroxyalkanoates, polypropylene, cotton, polyesters, polycaprolactone, polyvinylalcohol, polyacrylonitrile, polystyrene, poly(acrylic acid), polypropylene, protein based plastics, gelatine, and other biocompatible polymers, and combinations thereof, for regulating and/or controlling elution of NO.

30. Medical device according claim 28, wherein said nano-particles, micro-spheres, are or said powder is integrated in a gel, hydrogel, pill, tablet, capsule, foam, solution, or suspension, and combinations thereof.

31. Medical device according claim 28, wherein said granules, nano-particles, micro-spheres, are or said powder is of a material, selected from the group consisting of polyesters, polyamides, polyethers, polyurethanes, polycarbonates, polyvinylacetates, polylacticacids, starch, cellulose, polyhydroxyalkanoates, polypropylene, cotton, polyesters, polycaprolactone, polyvinylalcohol, polyacrylonitrile, polystyrene, poly(acrylic acid), polypropylene, protein based plastics, gelatine, and other biocompatible polymers, and combinations thereof, integrated, or covered, with said NO-eluting polymer.

32. Medical device according to any of claims 7 to 9 or 28, wherein said elution of said therapeutic dosage of nitric oxide (NO) from said nitric oxide (NO) eluting polymer is regulateable by means of a physical form or shape of said nitric oxide (NO) eluting polymer.

33. Medical device according to any of claims 7 to 32, wherein said composition is configured to elute NO when subjected to a proton donor.

34. Medical device according to claim 33, wherein said proton donor is moisture, water, or a body fluid in said urinary tract.

35. Medical device according to claim 33, wherein said composition is configured to immediately elute said nitric oxide upon contact with said proton donor in said urinary tract.

36. Medical device according to any of claims 7 to 9 or 33, wherein said elution of said therapeutic dosage of nitric oxide (NO) from said nitric oxide (NO) eluting polymer is regulateable by means of a proton donor.

37. Medical device according to any of the preceding claims 7 to 36, wherein said nitric oxide (NO) eluting polymer further is combined with silver, configured for said therapeutical target treatment, prophylactical treatment and/or prevention of cancer and/or infection in the urinary tract.

38. Medical device according to any of the preceding claims 7 to 37, wherein said nitric oxide (NO) eluting polymer is configured to act as a booster for pharmaceuticals, vitamins, and drugs, or combinations thereof.

39. Medical device according to claims 7 to 9 or claim 38, wherein said composition is combined with silver.

40. Medical device according to any of the preceding claims 7 to 39, wherein said composition is combined with a chemotherapeutic agent.

41. Medical device according to any of the preceding claims 7 to 40, wherein said composition comprises a hydrophobic alcohol.

42. Medical device according to claim 41, wherein said hydrophobic alcohol is lauryl alcohol.

43. A manufacturing process for a composition comprised in said medical device according to any of the preceding claims 7 to 42, said manufacturing process comprising

selecting a plurality of nitric oxide eluting polymeric particles, such as nano-fibers, nano-particles or micro-spheres, and

deploying said nitric oxide eluting polymeric particles into a suitable form or as a coating onto a carrier, to form a material comprised in said composition.

44. Manufacturing process according to claim 43, further comprising

selecting a nitric oxide (NO) eluting polymer configured to elute a therapeutic dosage of nitric oxide (NO) when used for said therapeutically target treatment, prophylactically treatment and/or prevention of cancer and/or infection in the urinary tract,

selecting a carrier material, which carrier material is configured to regulate and control the elution of said therapeutic dosage of nitric oxide (NO),

incorporating the NO-eluting polymer with said carrier material into an nitric oxide (NO) eluting material, such that said carrier material, in use of said device, regulates and controls the elution of said therapeutic dosage of nitric oxide (NO), and

deploying said nitric oxide eluting material into a suitable form, or as a coating onto a carrier, to form at least a part of said device, such that said device is configured to expose a therapeutic target site to said nitric oxide when said NO-eluting polymer in use elutes nitric oxide (NO).

45. The manufacturing process according to claim 43 or 44,

wherein said deploying comprises electro spinning, air spinning, gas spinning, wet spinning, dry spinning, melt spinning, or gel spinning of NO-eluting polymer.

46. Manufacturing process according to claim 43, further comprising

selecting a nitric oxide (NO) eluting polymer configured to elute a therapeutic dosage of nitric oxide (NO) when used for said therapeutically target treatment, prophylactically treatment and/or prevention of cancer and/or infection in the urinary tract,

selecting a liquid material, which liquid material is configured to regulate and control the elution of said therapeutic dosage of nitric oxide (NO),

incorporating the NO-eluting polymer with said liquid material into an nitric oxide

(NO) eluting material, such that said liquid material, in use of said device, regulates and controls the elution of said therapeutic dosage of nitric oxide (NO), and

deploying said nitric oxide eluting material into a solution or suspension with said liquid material, to form at least a part of said device, such that said device is configured to expose a therapeutic target site to said nitric oxide when said NO-eluting polymer in use elutes nitric oxide (NO).

47. The manufacturing process according to any of claims 43 to 46, wherein said selecting said nitric oxide (NO) eluting polymer comprises selecting a plurality of nitric oxide (NO) eluting polymeric particles, such as nano-fibers, nano-particles, micro-spheres or powder.

48. The manufacturing process according to any of claims 43 to 47, wherein said incorporating said NO-eluting polymer with said carrier material comprises integrating said NO-eluting polymer in said carrier material, spinning said NO-eluting polymer together with said carrier material, or spinning said NO-eluting polymer on top of said carrier material, in order to predefine nitric oxide eluting characteristics of said device.

49. The manufacturing process according to any of claims 43 to 48, further comprising integrating silver in said device.

50. The manufacturing process according to any of claims 43 to 49, further comprising selecting a pharmaceutical, vitamin, drug or a combination of theses, for which said nitric oxide (NO) eluting polymer is configured to act as a booster.

51. A method of a treatment and/or prevention of cancer and/or infection in the urinary tract, comprising using a composition comprising a nitric oxide (NO) eluting polymer configured for eluting a therapeutic dosage of nitric oxide (NO) when used for said treatment and/or prevention, comprising exposing a site in the urinary tract to said nitric oxide when said polymer in use elutes nitric oxide (NO) by eluting a therapeutic dose of nitric oxide from said nitric oxide eluting polymer to said urinary tract.

52. The method according to claim 51, wherein said method further comprises lowering the pH in the urinary tract during treatment with the NO eluting composition.

53. The method according to claim 52, comprising

accomplishing said lowering of the pH value by addition of a pH-adjusting agent, such as ammonium chloride, ammonium sulphate, a biological acceptable acid, or a combination of several pH-adjusting agents.

54. The method according to claim 51 comprising injecting said composition a catheter through the urethra to the urinary tract, such as to the bladder.

55. The method according to claim 54, wherein said composition is in a form selected from the group consisting of powder, nano-particles or micro-spheres, said method comprising

mixing said nano-particles or micro-spheres before said injecting with a solvent, said solvent having a proton donor capability, and

obtaining elution of NO inside the urinary tract.

56. The method according to claim 54, wherein said composition is in a form selected from the group consisting of powder, nano-particles or micro-spheres, said method comprising

mixing said nano-particles or micro-spheres before said injecting with a hydrophobic solvent, and

starting the elution of NO starts when the nano-particles, micro-spheres, or powder of NO eluting polymer gets in contact with the water or moisture in the urinary tract.

57. The method according to claim 56, comprising mixing said hydrophobic solvent/nitric oxide eluting polymer mixture with a water based gel for forming an emulsion to regulate and/or control the elution of nitric oxide.

58. The method according to claim 51, wherein said composition is in a form selected from the group consisting of powder, nano-particles or micro-spheres, encapsulated, or integrated, in a material, and

dissolving or breaking said encapsulation material in the urinary tract to start eluting said NO in the urinary tract of the patient for said treatment and/or prevention of cancer and/or infection in the urinary tract.

59. The method according to claim 51, wherein said method comprises applying nano-particles, micro-spheres, or powder as a pill, a tablet, a pellet, a capsule, composition, a gel, a hydrogel, a foam, a cream, and/or granules, to said site for said exposure.

60. The method according to any of claims 51 to 59, wherein said method further comprises adding an antioxidant to said urinary tract.

61. The method according to claim 51, comprising said NO-eluting composition acting as a booster for, pharmaceuticals, chemotherapeutic agent, vitamins, nicotine, or nitroglycerin.

62. The method according to claim 51, comprising

stimulating or inhibiting different cells of the immune system for boosting a chemotherapeutic substance or to counteract adverse effects of the chemotherapeutic substance.

63. The method according to claim 51, wherein said eluting of said nitric oxide (NO) comprises,

applying a urinary catheter in said urinary tract, said urinary catheter having a catheter balloon comprising a wall that is permeable for said nitric oxide (NO), and

eluting said nitric oxide (NO) from said composition to said urinary tract through said wall.

64. Use of nitric oxide (NO) in a therapeutic dose for therapeutically treating cancer in the urinary tract.

65. Use of a composition for a treatment and/or prevention of cancer and/or infection in a urinary tract, wherein said composition is configured to therapeutically target treat, prophylactically treat and/or prevent cancer and/or infection in the urinary tract, wherein

said composition is configured to elute nitric oxide (NO) in a therapeutic dosage, and wherein said composition is configured to expose the urinary tract to said eluted nitric oxide, and wherein

said composition comprises a nitric oxide (NO) eluting polymer configured to elute a therapeutic dosage of nitric oxide (NO) to expose an area of treatment in the urinary tract to said nitric oxide when said polymer in use elutes nitric oxide (NO), and

wherein elution of said therapeutic dosage of nitric oxide (NO) from said nitric oxide (NO) eluting polymer is regulateable.