Claims
- 1. A controlled release drug delivery composition comprising at least one polycationic polymer complexed with at least one first negatively charged pharmacologically active agent to provide controllable release of at least the first negatively charged pharmacologically active agent when administered to a patient.
- 2. The composition of claim 1 wherein the composition further comprises at least one pharmaceutically acceptable carrier or excipient.
- 3. The composition of claim 1 wherein the composition further comprises at least one pharmaceutically acceptable carrier or excipient that further comprises at least a second pharmacologically active agent.
- 4. The composition of claim 2 or 3 wherein the polycationic polymer comprises chitosan.
- 5. The composition of claim 2 or 3 wherein the first negatively charged pharmacologically active agent comprises a negatively charged oligonucleotide.
- 6. The composition of claim 5 wherein the negatively charged oligonucleotide comprises one or more of the group of antisense oligonucleotide, ribozyme, oligonucleotide RNA inhibitor, immune modulating oligonucleotide and nonspecific oligonucleotide.
- 7. The composition of claim 2 or 3 wherein the polycationic polymer comprises chitosan and the first negatively charged pharmacologically active agent comprises a negatively charged oligonucleotide.
- 8. The composition of claim 2 or 3 wherein the polycationic polymer comprises chitosan and the first negatively charged pharmacologically active agent comprises a negatively charged oligonucleotide and the chitosan-negatively charged oligonucleotide complex is in the form of a solution, gel, sol, suspension, spray, mousse, lotion, cream, ointment, paste, slurry, particulate, microparticulate, microsphere, film or slab within the composition.
- 9. The composition of claim 8 wherein the chitosan-negatively charged oligonucleotide complex is in the form of a particulate, microparticulate or microsphere within the composition.
- 10. The composition of claim 2 or 3 wherein the composition is a solution, gel, sol, suspension, spray, mousse, lotion, cream, ointment, paste, slurry, particulate, microparticulate, microsphere, film, slab, wrap, barrier or implant.
- 11. The composition of claim 10 wherein the composition is a paste.
- 12. The composition of claim 10 wherein the composition is a film less than about 2 mm thick.
- 13. The composition of claim 2 or 3 wherein the pharmaceutically acceptable carrier or excipient is a polymeric carrier.
- 14. The composition of claim 3 wherein the pharmaceutically acceptable carrier or excipient is a polymeric carrier that provides controllable release of at least one of the second pharmacologically active agent and the first negatively charged pharmacologically active agent.
- 15. The composition of claim 14 wherein the pharmaceutically acceptable carrier or excipient is a polymeric carrier that provides controllable release of the second pharmacologically active agent.
- 16. The composition of claim 2 or 14 wherein the composition is formulated to release greater than about 10% w/w of the first negatively charged pharmacologically active agent over a period of about 5 to 15 days.
- 17. The composition of claim 2 or 14 wherein the composition is formulated to release less than about 10% w/w of the first negatively charged pharmacologically active agent over a period of about 5 to 15 days.
- 18. The composition of claim 15 wherein the composition is formulated to release greater than about 10% w/w of the second pharmacologically active agent over a period of about 5 to 15 days.
- 19. The composition of claim 15 wherein the composition is formulated to release less than about 10% w/w of the second pharmacologically active agent over a period of about 5 to 15 days.
- 20. The composition of claim 3 or 14 wherein the second pharmacologically active agent comprises at least one of paclitaxel, docetaxol, mitoxantrone, cisplatin or methotrexate.
- 21. The composition of claim 20 wherein the second pharmacologically active agent comprises at least one of paclitaxel or docetaxol.
- 22. The composition of claim 2 or 3 wherein the composition is sized and formulated for intraperitoneal, intraarticular, intraocular, intratumoral, perivascular, subcutaneous, intracranial, intramuscular, intravenous, periophthalmic, inside the eyelid, intraoral, intranasal, intrabladder, intravaginal, intraurethral, intrarectal, adventitial, oral, nasal, rectal or topical administration to a patient.
- 23. The composition of claim 22 wherein the composition is sized and formulated for intraperitoneal, intraarticular, intraocular, intratumoral, perivascular, subcutaneous, intracranial, intramuscular, intravenous, periophthalmic, inside the eyelid, intraoral, intranasal, intrabladder, intravaginal, intraurethral, intrarectal or adventitial administration to a patient.
- 23. The composition of claim 22 wherein the composition is sized and formulated for oral, nasal or rectal administration to a patient.
- 24. The composition of claim 22 wherein the composition is sized and formulated for topical administration to a patient.
- 25. The composition of claim 2 or 3 wherein the composition is sized and formulated to be injected through a syringe needle.
- 26. The composition of claim 2 or 3 wherein the composition further comprises a cell permeation enhancing agent.
- 27. The composition of claim 2 or 3 wherein the composition further provides protection of the first negatively charged pharmacologically active agent from degradation.
- 28. The composition of claim 2 or 3 wherein the patient is a mammal.
- 29. The composition of claim 28 wherein the mammal is a human.
- 30. The composition of claim 29 wherein the mammal is a cow, horse, sheep, dog or cat.
- 31. The composition of claim 2 or 3 wherein the polycationic polymer-first negatively charged pharmacologically active agent complex is an ionic complex.
- 32. The composition of claim 2 or 3 wherein the polycationic polymer comprises at least one of a polyaminoacid, polyquaternary compound, protamine, polyvinylpyridine, polythiodiethylaminomethyl-ethylene, poly-p-aminostyrene, polycationic carbohydrate, polyimine, polycationic polymer derivatized with DEAE, polycationic polymethacrylate, polycationic polyacrylate, polycationic polyoxethane, polyamidoamine, polylysine, polyhistidine and polycationic starch.
- 33. The composition of claim 2 or 3 wherein the first negatively charged pharmacologically active agent is at least one of an anti-hepatitis agent, anti-diabetic, anti-ocular disease agent, anti-microbial, anti-viral, anti-fungal, anesthetic, anti-vascular disease agent, anti-restenotic, anti-stenotic, vasoconstrictor, vasodilator, cardiotonic, enzyme, anti-inflammatory, anti-post surgical adhesion agent, anti-psoriatic, anti-arthritic, anti-multiple sclerosis agent, anti-inflammatory bowel disease agent, hormone, bone metabolism controlling agent, hypotensive, hypertensive, sedative, anti-cancer agent, antihistamine, antitussive, vaccine, anti-neural disorder agent and asthma treatment.
- 33. The composition of claim 2 or 3 wherein the second pharmacologically active agent is at least one of an anti-hepatitis agent, anti-diabetic, anti-ocular disease agent, anti-microbial, anti-viral, anti-fungal, anesthetic, anti-vascular disease agent, anti-restenotic, anti-stenotic, vasoconstrictor, vasodilator, cardiotonic, enzyme, anti-inflammatory, anti-post surgical adhesion agent, anti-psoriatic, anti-arthritic, anti-multiple sclerosis agent, anti-inflammatory bowel disease agent, hormone, bone metabolism controlling agent, hypotensive, hypertensive, sedative, anti-cancer agent, antihistamine, antitussive, vaccine, anti-neural disorder agent and asthma treatment.
- 34. A surgical device suitable for implantation in a patient comprising a composition according to claim 2 or 3.
- 35. The surgical device of claim 34 wherein the surgical device is a catheter, shunt, device for continuous subarachnoid infusion, feeding tube, solid implant to prevent surgical adhesion, uterine implant, artificial sphincter, periurethral implant, splint, ophthalmic implant, contact lens, plastic surgery implant, stent including an esophageal stent, gastrointestinal stent, vascular stent, biliary stent, colonic stent, pancreatic stent, ureteric stent, urethral stent, lacrimal stent, Eustachian tube stent, fallopian tube stent, nasal stent, sinus stents, tracheal stent or bronchial stent, or a port including a venous access device comprising an external tunneled catheter, implanted port, epidural catheter or central catheter (PICC).
- 36. A kit comprising a composition according to claim 2 or 3 in a pharmaceutically acceptable container.
- 37. The kit of claim 36 wherein the kit further comprises a notice associated with the container, the notice in a form prescribed by a governing agency regulating the composition.
- 38. The kit of claim 36 wherein the kit further comprises instructions about at least one of use of the composition, dosing a patient or mode of administration.
- 39. A method of manufacturing a controlled release drug delivery composition comprising complexing at least one polycationic polymer with at least one first negatively charged pharmacologically active agent to provide controllable release of at least the first negatively charged pharmacologically active agent when administered to a patient.
- 40. The method of claim 39 wherein the method further comprises mixing, blending, dissolving, associating or incorporating the polycationic polymer-first negatively charged pharmacologically active agent complex with at least one pharmaceutically acceptable carrier or excipient.
- 41. The method of claim 39 wherein the method further comprises mixing, blending, dissolving, associating or incorporating the polycationic polymer-first negatively charged pharmacologically active agent complex with at least one pharmaceutically acceptable carrier or excipient that further comprises at least a second pharmacologically active agent.
- 42. The method of claim 40 or 41 wherein the polycationic polymer comprises chitosan.
- 43. The method of claim 40 or 41 wherein the first negatively charged pharmacologically active agent comprises a negatively charged oligonucleotide.
- 44. The method of claim 43 wherein the negatively charged oligonucleotide comprises one or more of the group of antisense oligonucleotide, ribozyme, oligonucleotide RNA inhibitor, immune modulating oligonucleotide and nonspecific oligonucleotide.
- 45. The method of claim 40 or 41 wherein the polycationic polymer comprises chitosan and the first negatively charged pharmacologically active agent comprises a negatively charged oligonucleotide.
- 46. The method of claim 40 or 41 wherein the polycationic polymer comprises chitosan and the first negatively charged pharmacologically active agent comprises a negatively charged oligonucleotide and the chitosan-negatively charged oligonucleotide complex is in the form of a solution, gel, sol, suspension, spray, mousse, lotion, cream, ointment, paste, slurry, particulate, microparticulate, microsphere, film or slab within the composition.
- 47. The method of claim 46 wherein the chitosan-negatively charged oligonucleotide complex is in the form of a particulate, microparticulate or microsphere within the composition.
- 48. The method of claim 40 or 41 wherein the composition is a solution, gel, sol, suspension, spray, mousse, lotion, cream, ointment, paste, slurry, particulate, microparticulate, microsphere, film, slab, wrap, barrier or implant.
- 49. The method of claim 48 wherein the composition is a paste.
- 50. The method of claim 48 wherein the composition is a film less than about 2 mm thick.
- 51. The method of claim 40 or 41 wherein the pharmaceutically acceptable carrier or excipient is a polymeric carrier.
- 52. The method of claim 41 wherein the pharmaceutically acceptable carrier or excipient is a polymeric carrier that provides controllable release of at least one of the second pharmacologically active agent and the first negatively charged pharmacologically active agent.
- 53. The method of claim 52 wherein the pharmaceutically acceptable carrier or excipient is a polymeric carrier that provides controllable release of the second pharmacologically active agent.
- 54. The method of claim 40 or 52 wherein the composition is formulated to release greater than about 10% w/w of the first negatively charged pharmacologically active agent over a period of about 5 to 15 days.
- 55. The method of claim 40 or 52 wherein the composition is formulated to release less than about 10% w/w of the first negatively charged pharmacologically active agent over a period of about 5 to 15 days.
- 56. The method of claim 53 wherein the composition is formulated to release greater than about 10% w/w of the second pharmacologically active agent over a period of about 5 to 15 days.
- 57. The method of claim 53 wherein the composition is formulated to release less than about 10% w/w of the second pharmacologically active agent over a period of about 5 to 15 days.
- 58. The method of claim 41 or 52 wherein the second pharmacologically active agent comprises at least one of paclitaxel, docetaxol, mitoxantrone, cisplatin or methotrexate.
- 59. The method of claim 58 wherein the second pharmacologically active agent comprises at least one of paclitaxel or docetaxol.
- 60. The method of claim 40 or 41 wherein the composition is sized and formulated for intraperitoneal, intraarticular, intraocular, intratumoral, perivascular, subcutaneous, intracranial, intramuscular, intravenous, periophthalmic, inside the eyelid, intraoral, intranasal, intrabladder, intravaginal, intraurethral, intrarectal, adventitial, oral, nasal, rectal or topical administration to a patient.
- 61. The method of claim 60 wherein the composition is sized and formulated for intraperitoneal, intraarticular, intraocular, intratumoral, perivascular, subcutaneous, intracranial, intramuscular, intravenous, periophthalmic, inside the eyelid, intraoral, intranasal, intrabladder, intravaginal, intraurethral, intrarectal or adventitial administration to a patient.
- 62. The method of claim 61 wherein the composition is sized and formulated for oral, nasal or rectal administration to a patient.
- 63. The method of claim 61 wherein the composition is sized and formulated for topical administration to a patient.
- 64. The method of claim 40 or 41 wherein the composition is sized and formulated to be injected through a syringe needle.
- 65. The method of claim 40 or 41 wherein the composition further comprises a cell permeation enhancing agent.
- 66. The method of claim 40 or 41 wherein the composition further provides protection of the first negatively charged pharmacologically active agent from degradation.
- 67. The method of claim 40 or 41 wherein the patient is a mammal.
- 68. The method of claim 40 or 41 wherein the mammal is a human.
- 69. The method of claim 68 wherein the mammal is a cow, horse, sheep, dog or cat.
- 70. The method of claim 40 or 41 wherein the polycationic polymer-first negatively charged pharmacologically active agent complex is an ionic complex.
- 71. The method of claim 40 or 41 wherein the polycationic polymer comprises at least one of a polyaminoacid, polyquaternary compound, protamine, polyvinylpyridine, polythiodiethylaminomethyl-ethylene, poly-p-aminostyrene, polycationic carbohydrate, polyimine, polycationic polymer derivatized with DEAE, polycationic polymethacrylate, polycationic polyacrylate, polycationic polyoxethane, polyamidoamine, polylysine, polyhistidine and polycationic starch.
- 72. A method of at least one of treating, preventing or inhibiting at least one of a proliferative disease or inflammatory disease comprising administering to a patient at least potentially having the disease a therapeutically effective amount of the composition of any one of claims 1, 2 or 3.
- 73. A method of at least one of treating, preventing or inhibiting at least one of a proliferative disease or inflammatory disease comprising administering to a patient, the method comprising administering a controlled release drug delivery composition produced according to any one of claims 39 to 53 to the patient.
- 74. The method of claim 73 wherein the composition is administered by at least one of topically, via injection through a syringe needle, intra-tumorally into a tumor, or by implanting a surgical device comprising the composition.
- 75. An isolated and purified composition according to any one of claims 1 to 3 for use in the manufacture of a medicament for inhibiting, preventing, or treating a proliferative or inflammatory disease in a human patient.
- 76. The composition of claim 75 wherein the disease is selected from the group consisting of cancer, arthritis, psoriasis or surgical adhesion.
- 77. The method of claim 40 or 41 wherein the method further comprises adding the composition to a surgical device suitable for implantation in a patient.
- 78. The method of claim 77 wherein the surgical device is a catheter, shunt, device for continuous subarachnoid infusion, feeding tube, solid implant to prevent surgical adhesion, uterine implant, artificial sphincter, periurethral implant, splint, ophthalmic implant, contact lens, plastic surgery implant, stent including an esophageal stent, gastrointestinal stent, vascular stent, biliary stent, colonic stent, pancreatic stent, ureteric stent, urethral stent, lacrimal stent, Eustachian tube stent, fallopian tube stent, nasal stent, sinus stents, tracheal stent or bronchial stent, or a port including a venous access device comprising an external tunneled catheter, implanted port, epidural catheter or central catheter (PICC).
- 79. The method of claim 40 or 41 wherein the method further comprises adjusting the ratio of polycationic polymer to first negatively charged pharmacologically active agent to provide a desired rate of release of the first negatively charged pharmacologically active agent from the composition.
- 80. The method of claim 52 wherein the method further comprises adjusting the ratio of polymeric carrier to first negatively charged pharmacologically active agent to provide a desired rate of release of the first negatively charged pharmacologically active agent from the composition.
- 81. The method of claim 53 wherein the method further comprises adjusting the ratio of polymeric carrier to second pharmacologically active agent to provide a desired rate of release of the second pharmacologically active agent from the composition.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims priority from U.S. provisional patent application No. 60/328,175, filed Oct. 9, 2001, and from U.S. provisional patent application No. 60/328,208, filed Oct. 9, 2001.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60328175 |
Oct 2001 |
US |
|
60328203 |
Oct 2001 |
US |