CA2453442A1 - Compositions and methods of administering tubulin binding agents for the treatment of ocular diseases - Google Patents
Compositions and methods of administering tubulin binding agents for the treatment of ocular diseases Download PDFInfo
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- CA2453442A1 CA2453442A1 CA002453442A CA2453442A CA2453442A1 CA 2453442 A1 CA2453442 A1 CA 2453442A1 CA 002453442 A CA002453442 A CA 002453442A CA 2453442 A CA2453442 A CA 2453442A CA 2453442 A1 CA2453442 A1 CA 2453442A1
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- combretastatin
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- 239000011230 binding agent Substances 0.000 title claims abstract 24
- 102000004243 Tubulin Human genes 0.000 title claims abstract 23
- 108090000704 Tubulin Proteins 0.000 title claims abstract 23
- 238000000034 method Methods 0.000 title claims 45
- 208000022873 Ocular disease Diseases 0.000 title claims 30
- 239000000203 mixture Substances 0.000 title claims 7
- 206010029113 Neovascularisation Diseases 0.000 claims abstract 33
- 208000024519 eye neoplasm Diseases 0.000 claims abstract 12
- 201000008106 ocular cancer Diseases 0.000 claims abstract 12
- 201000000582 Retinoblastoma Diseases 0.000 claims abstract 9
- 206010012689 Diabetic retinopathy Diseases 0.000 claims abstract 8
- 206010038933 Retinopathy of prematurity Diseases 0.000 claims abstract 8
- 208000002780 macular degeneration Diseases 0.000 claims abstract 8
- HVXBOLULGPECHP-WAYWQWQTSA-N Combretastatin A4 Chemical group C1=C(O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-WAYWQWQTSA-N 0.000 claims 36
- 229960005537 combretastatin A-4 Drugs 0.000 claims 36
- HVXBOLULGPECHP-UHFFFAOYSA-N combretastatin A4 Natural products C1=C(O)C(OC)=CC=C1C=CC1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-UHFFFAOYSA-N 0.000 claims 36
- 239000000651 prodrug Substances 0.000 claims 32
- 229940002612 prodrug Drugs 0.000 claims 32
- 239000008194 pharmaceutical composition Substances 0.000 claims 28
- 238000002347 injection Methods 0.000 claims 16
- 239000007924 injection Substances 0.000 claims 16
- 239000003814 drug Substances 0.000 claims 15
- 239000002552 dosage form Substances 0.000 claims 12
- 206010051625 Conjunctival hyperaemia Diseases 0.000 claims 8
- 210000003161 choroid Anatomy 0.000 claims 8
- 229940012356 eye drops Drugs 0.000 claims 8
- 239000007943 implant Substances 0.000 claims 8
- 201000005111 ocular hyperemia Diseases 0.000 claims 8
- 210000001525 retina Anatomy 0.000 claims 8
- 210000004087 cornea Anatomy 0.000 claims 7
- 241000124008 Mammalia Species 0.000 claims 6
- 239000003885 eye ointment Substances 0.000 claims 6
- 229940100655 ophthalmic gel Drugs 0.000 claims 6
- 229940069265 ophthalmic ointment Drugs 0.000 claims 6
- 239000003937 drug carrier Substances 0.000 claims 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims 4
- 239000002671 adjuvant Substances 0.000 claims 3
- 239000003085 diluting agent Substances 0.000 claims 3
- 208000016623 Choroid neoplasm Diseases 0.000 claims 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 2
- 238000011200 topical administration Methods 0.000 claims 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims 1
- 206010061252 Intraocular melanoma Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 201000005969 Uveal melanoma Diseases 0.000 claims 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims 1
- 239000001768 carboxy methyl cellulose Substances 0.000 claims 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims 1
- 229960005527 combretastatin A-4 phosphate Drugs 0.000 claims 1
- WDOGQTQEKVLZIJ-WAYWQWQTSA-N combretastatin a-4 phosphate Chemical compound C1=C(OP(O)(O)=O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 WDOGQTQEKVLZIJ-WAYWQWQTSA-N 0.000 claims 1
- 239000000839 emulsion Substances 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 201000002575 ocular melanoma Diseases 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 230000002792 vascular Effects 0.000 abstract 1
Classifications
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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
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention is directed to the administration of vascular targetin g agents, particularly a tubulin binding agent, for the treatment of ocular neovascularization, ocular tumors, and conditions such as diabetic retinopathy, retinopathy of prematurity, retinoblastoma and macular degeneration.
Claims (95)
1. A method for the treatment of ocular disease, the method comprising the steps of:
a) preparing a dosage comprising a pharmaceutically effective dosage of a tubulin binding agent;
b) administering the pharmaceutically effective dosage to a subject in need thereof.
a) preparing a dosage comprising a pharmaceutically effective dosage of a tubulin binding agent;
b) administering the pharmaceutically effective dosage to a subject in need thereof.
2. The method as recited in claim 1, wherein said tubulin binding agent is combretastatin A4.
3. The method as recited in claim 1, wherein said tubulin binding agent is combretastatin A4 prodrug.
4. The method as recited in claim 1, wherein said ocular disease may include neovascularization of the retina, neovascularization of the choroid and neovascularization of ocular tumors.
5. The method as recited in claim 1, wherein said ocular disease may include diabetic retinopathy, retinopathy of prematurity, and retinoblastoma .
6. The method as recited in claim 1, wherein said ocular disease may include neovascularization of the cornea and macular degeneration.
7. The method as recited in claim 1, wherein said pharmaceutically effective dosage is administered non-systemically to the eye of said subject.
8. The method as recited in claim 1, wherein said pharmaceutically effective dosage is administered non-systemically to the eye via intravitreal injection, sub-conjunctival injection, peri-ocular injection, sub-Tenon's injection, via ophthalmic drops, via ophthalmic gel, via ophthalmic ointment, via iontophoresis and via ocular implant and/or ocular insert.
9. The method as recited in claim 7, wherein said pharmaceutically effective dosage administered non-systemically comprises an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/ml to approximately 100 mg/ml.
10. The method as recited in claim 1, wherein said pharmaceutically effective dosage is systemically administered to said subject.
11. The method as recited in claim 1, wherein said pharmaceutically effective dosage is administered parenterally.
12. The method as recited in claim 10, wherein said pharmaceutically effective dosage administered systemically comprises an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/m2 to approximately 120 mg/m2.
13. The method as recited in claim 1, wherein said subject is a mammal.
14. A pharmaceutical medicament for the treatment of ocular disease, comprising a therapeutically effective amount of a tubulin binding agent for reducing ocular neovascularization in association with a pharmaceutically acceptable carrier, excipient, diluent or adjuvant for administration to a subject in need thereof.
15. The pharmaceutical medicament as recited in claim 14, wherein said tubulin binding agent is combretastatin A4.
16. The pharmaceutical medicament as recited in claim 14, wherein said tubulin binding agent is combretastatin A4 prodrug.
17. The pharmaceutical medicament as recited in claim 14, wherein said ocular disease may include neovascularization of the retina, neovascularization of the choroid and neovascularization of ocular tumors.
18. The pharmaceutical medicament as recited in claim 14, wherein said ocular disease may include diabetic retinopathy, retinopathy of prematurity, and retinoblastoma.
19. The pharmaceutical medicament as recited in claim 14, wherein said ocular disease may include neovascularization of the cornea and macular degeneration.
20. The pharmaceutical medicament as recited in claim 14, wherein said therapeutically effective amount is administered non-systemically to the eye of said subject.
21. The pharmaceutical medicament as recited in claim 13, wherein said therapeutically effective amount is administered non-systemically to the eye via intravitreal injection, sub-conjunctival injection, peri-ocular injection, sub-Tenon's injection, via ophthalmic drops, via iontophoresis and via ocular implant and/or ocular insert.
22. The pharmaceutical medicament as recited in claim 20, wherein said pharmaceutically effective dosage administered non-systemically comprises an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/ml to approximately 100 mg/ml.
23. The pharmaceutical medicament as recited in claim 14, wherein said pharmaceutically effective dosage is systemically administered to said subject.
24. The pharmaceutical medicament as recited in 14, wherein said pharmaceutically effective dosage is administered parenterally.
25. The pharmaceutical medicament as recited in claim 23, wherein said pharmaceutically effective dosage administered systemically comprises an amount of combretastatinA4 prodrug in the range of from approximately 0.1 mg/m2 to approximately 120 mg/m2.
26. The pharmaceutical medicament as recited in claim 14, wherein said subject is a mammal.
27. A method of treating or preventing ocular neovascularization in a subject, the method comprising administering to said subject a pharmaceutically effective dosage of a tubulin binding agent.
28. The method as recited in claim 27, wherein said tubulin binding agent is combretastatin A4.
29. The method as recited in claim 27, wherein said tubulin binding agent is combretastatin A4 prodrug.
30. The method as recited in claim 27, wherein said ocular neovascularization may include neovascularization of the retina, neovascularization of the choroid and neovascularization of ocular tumors.
31. The method as recited in claim 27, wherein said pharmaceutically effective dosage is administered non-systemically to the eye of said subject.
32. The method as recited in claim 27, wherein said pharmaceutically effective dosage is administered non-systemically to the eye via intravitreal injection, sub-conjunctival injection, peri-ocular injection, sub-Tenon's injection, via ophthalmic drops, via iontophoresis and via ocular implant and/or ocular insert.
33. The method as recited in claim 31, wherein said pharmaceutically effective dosage administered non-systemically comprises an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/ml to approximately 100 mg/ml.
34. The method as recited in claim 27, wherein said pharmaceutically effective dosage is systemically administered to said subject.
35. The method as recited in 30, wherein said pharmaceutically effective dosage is administered parenterally.
36. The method as recited in claim 34, wherein said pharmaceutically effective dosage administered systemically comprises an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/m2 to approximately 120 mg/m2.
37. The method as recited in claim 30, wherein said subject is a mammal.
38. A method of treating or preventing ocular tumors, the method comprising administering a pharmaceutically effective dosage of a tubulin binding agent to a subject in need thereof.
39. The method as recited in claim 38, wherein said tubulin binding agent is combretastatin A4.
40. The method as recited in claim 38, wherein said tubulin binding agent is combretastatin A4 prodrug.
41. The method as recited in claim 38, wherein said ocular tumors may include retinoblastoma, primary ocular lymphoma, choroidal melanoma and intraocular melanoma.
42. The method as recited in claim 38, wherein said pharmaceutically effective dosage is administered non-systemically to the eye of said subject.
43. The method as recited in claim 38, wherein said pharmaceutically effective dosage is administered non-systemically to the eye via intravitreal injection, sub-conjunctival injection, peri-ocular injection, sub-Tenon's injection, via ophthalmic drops, via ophthalmic gel, via ophthalmic ointment, via iontophoresis and via ocular implant and/or ocular insert.
44. The method as recited in claim 42, wherein said pharmaceutically effective dosage administered non-systemically comprises an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/ml to approximately 100 mg/ml.
45. The method as recited in claim 38, wherein said pharmaceutically effective dosage is systemically administered to said subject.
46. The method as recited in 38, wherein said pharmaceutically effective dosage is administered parenterally.
47 47. The method as recited in claim 45, wherein said pharmaceutically effective dosage administered systemically comprises an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/m2 to approximately 120 mg/m2.
48. The method as recited in claim 38, wherein said subject is a mammal.
49. A pharmaceutical composition comprising a therapeutically effective amount of a tubulin binding agent for administration to a subject suffering from an ocular disease.
50. The pharmaceutical composition as recited in claim 49, wherein said tubufin binding agent is combretastatin A4.
51. The pharmaceutical composition as recited in claim 49, wherein said tubulin binding agent is combretastatin A4 prodrug.
52. The pharmaceutical composition as recited in claim 49, wherein said ocular disease may include neovascularization of the retina, neovascularization of the choroid and ocular tumors.
53. The pharmaceutical medicament as recited in claim 49, wherein said ocular disease may include diabetic retinopathy, retinopathy of prematurity, and retinoblastoma.
54. The pharmaceutical medicament as recited in claim 49, wherein said ocular disease may include neovascularization of the cornea and macular degeneration.
55. The pharmaceutical composition as recited in claim 49, wherein said therapeutically effective amount of said tubulin binding agent is administered non-systemically to the eye of said subject.
56. The pharmaceutical composition as recited in claim 49, wherein said composition is non-systemically administered to the eye of said subject via intravitreal injection, sub-conjunctival injection, peri-ocular injection, sub-Tenon's injection, via ophthalmic drops, via ophthalmic gel, ophthalmic ointment, via iontophoresis and via ocular implant and/or insert.
57. The pharmaceutical composition as recited in claim 55, wherein said therapeutically effective amount administered non-systemically comprises an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/ml to approximately 100 mg/ml.
58. The pharmaceutical composition as recited in claim 49, wherein said therapeutically effective amount of combretastatin A4 prodrug is systemically administered to said subject.
59. The pharmaceutical composition as recited in claim 49, wherein said therapeutically effective amount of combretastatin A4 prodrug is administered parenterally.
60. The pharmaceutical composition as recited in claim 58, wherein said therapeutically effective amount said administered systemically comprises an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/m2 to approximately 120 mg/m2.
61. The pharmaceutical composition as received in claim 49, wherein said subject is a mammal.
62. A pharmaceutical dosage form which comprises a therapeutically effective amount of combretastatin A4 prodrug and a pharmaceutically acceptable carrier or excipient for treating ocular diseases in a subject via administration of said dosage form to said subject.
63. The pharmaceutical dosage form as recited in claim 62, wherein said ocular diseases may include neovascularization of the retina, neovascularization of the choroid and ocular tumors.
64. The pharmaceutical dosage form as recited in claim 62, wherein said ocular diseases may include diabetic retinopathy, retinopathy of prematurity, and retinoblastoma.
65. The pharmaceutical dosage form as recited in claim 62, wherein said ocular disease may include neovascularization of the cornea and macular degeneration.
66. The pharmaceutical dosage form as recited in claim 62, wherein said therapeutically effective amount of combretastatin A4 prodrug is administered non-systemically to the eye of said subject.
67. The pharmaceutical dosage form as recited in claim 62, wherein said composition is non-systemically administered to the eye of said subject via intravitreal injection, sub-conjunctival injection, peri-ocular injection, sub-Tenon's injection, via ophthalmic drops, via ophthalmic gel, via ophthalmic ointment, via iontophoresis and via ocular implant and/or insert.
68. The pharmaceutical dosage form as recited in claim 66, wherein said therapeutically effective amount administered non-systemically comprises an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/ml to approximately 100 mg/ml.
69. The pharmaceutical dosage form as recited in claim 62, wherein said therapeutically effective amount of combretastatin A4 prodrug is systemically administered to said subject.
70. The pharmaceutical dosage form as recited in claim 62, wherein said therapeutically effective amount of combretastatin A4 prodrug is administered parenterally.
71. The pharmaceutical dosage form as recited in claim 69, wherein said therapeutically effective amount administered systemically comprises an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/m2 to approximately 120 mg/m2.
72. The pharmaceutical dosage form as received in claim 64, wherein said subject is a mammal.
73. A method of treating ocular diseases by administering a tubulin binding agent to the eye of a subject in need thereof in a dose sufficient to achieve a concentration of the tubulin binding agent in the eye in the range between approximately 1 nM to approximately 100 mM
of aqueous humour tissue.
of aqueous humour tissue.
74. The method as recited in claim 73, wherein said ocular diseases may include neovascularization of the retina, neovascularization of the choroid and neovascularization of ocular tumors.
75. The method as recited in claim 73, wherein said ocular diseases may include diabetic retinopathy, retinopathy of prematurity, and retinoblastoma.
76. The method as recited in claim 73, wherein said ocular diseases may include neovascularization of the cornea and macular degeneration.
77. The method as recited in claim 73, wherein said tubulin binding agent is combretastatin A4 prodrug.
78. The methods as recited in claim 73, wherein said tubulin binding agent is administered to the eye of said subject via intravitreal injection, sub-conjunctival injection, peri-ocular injection, sub-Tenon's injection, via ophthalmic drops, via ophthalmic gel, via ophthalmic ointment, via iontophoresis and via ocular implant and/or ocular insert.
79. A pharmaceutical composition for topical administration to the eye of subject afflicted with an ocular disease, comprising a tubulin binding agent in association with a pharmaceutically acceptable carrier, excipient, diluent or adjuvant for administration to a subject in need thereof.
80. The pharmaceutical composition as recited in claim 79, wherein said tubulin binding binding agent is combretastatin A4 prodrug.
81. The pharmaceutical composition as recited in claim 79, wherein said ocular disease may include neovascularization of the retina, neovascularization of the choroid and neovascularization of ocular tumors.
82. The pharmaceutical composition as recited in claim 79, wherein said ocular disease may include diabetic retinopathy, retinopathy of prematurity, and retinoblastoma.
83. The pharmaceutical composition as recited in claim 79, wherein said ocular diseases may include neovascularization of the cornea and macular degeneration.
84. The pharmaceutical composition as recited in claim 79, wherein said composition is administered non-systemically to the eye of said subject.
85. A pharmaceutical composition for topical administration to the eye of a subject afflicted with an ocular disease, the composition comprising in a suspension, emulsion or solution:
(a) an amount of CA4P in the range of from approximately 0.1 mg/ml to approximately 100 mg/ml;
(b) approximately 5 mg/ml carboxymethylcellulose; and (c) approximately 9mg/ml NaCl.
(a) an amount of CA4P in the range of from approximately 0.1 mg/ml to approximately 100 mg/ml;
(b) approximately 5 mg/ml carboxymethylcellulose; and (c) approximately 9mg/ml NaCl.
86. The pharmaceutical composition as recited in claim 85, wherein said composition has a final pH in the range of from approximately 6.6 to 8.6, osmolarity in the range of from approximately 291-492 mosmol/kg H2O and viscosity in the range of from approximately 50-66 mPa.s.
87. The pharmaceutical composition as recited in claim 85, wherein said ocular disease may include neovascularization of the retina, neovascularization of the choroid and neovascularization of ocular tumors.
88. The pharmaceutical composition as recited in claim 85, wherein said ocular disease may include diabetic retinopathy, retinopathy of prematurity, and retinoblastoma.
89. The pharmaceutical composition as recited in claim 85, wherein said ocular diseases may include neovascularization of the cornea and macular degeneration.
90. The pharmaceutical composition as recited in claim 85, wherein said composition is administered non-systemically to the eye of said subject.
91. A pharmaceutical composition for the treatment or prevention of ocular diseases and ocular tumors, comprising a therapeutically effective amount of combretastatin A4 prodrug in association with a pharmaceutically acceptable carrier, excipient, diluent or adjuvant for administration to a subject in need thereof.
92. The pharmaceutical composition as recited in claim 91, wherein said therapeutically effective amount of combretastatin A4 prodrug is non-systemically administered to the eye of said subject via intravitreal injection, sub-conjunctival injection, peri-ocular injection, sub-Tenon's injection, via ophthalmic drops, via ophthalmic gel, via ophthalmic ointment, via iontophoresis and via ocular implant and/or insert.
93. The pharmaceutical composition as recited in claim 91, wherein said therapeutically effective amount of combretastatin A4 prodrug is administered non-systemically to the eye of said subject in an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/ml to approximately 100 mg/ml.
94. The pharmaceutical composition as recited in claim 91, wherein said therapeutically effective amount of combretastatin A4 prodrug is systemically administered to said subject.
95. The pharmaceutical composition as recited in claim 91, wherein said therapeutically effective amount of combretastatin A4 prodrug is administered systemically to said subject in an amount of combretastatin A4 prodrug in the range of from approximately 0.1 mg/m2 to approximately 120 mg/m2.
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US38622701P | 2001-07-13 | 2001-07-13 | |
US60/386,227 | 2001-07-13 | ||
US37784702P | 2002-05-03 | 2002-05-03 | |
US37755602P | 2002-05-03 | 2002-05-03 | |
US37784502P | 2002-05-03 | 2002-05-03 | |
US60/377,845 | 2002-05-03 | ||
US60/377,847 | 2002-05-03 | ||
US60/377,556 | 2002-05-03 | ||
PCT/US2002/022449 WO2003006002A1 (en) | 2001-07-13 | 2002-07-15 | Compositions and methods of administering tubulin binding agents for the treatment of ocular diseases |
Publications (2)
Publication Number | Publication Date |
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CA2453442A1 true CA2453442A1 (en) | 2003-01-23 |
CA2453442C CA2453442C (en) | 2011-02-01 |
Family
ID=32034390
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CA2453442A Expired - Fee Related CA2453442C (en) | 2001-07-13 | 2002-07-15 | Compositions and methods of administering tubulin binding agents for the treatment of ocular diseases |
Country Status (8)
Country | Link |
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EP (1) | EP1406600A4 (en) |
JP (2) | JP2004536847A (en) |
KR (1) | KR20040030042A (en) |
CN (1) | CN1527704B (en) |
CA (1) | CA2453442C (en) |
NZ (1) | NZ575466A (en) |
WO (1) | WO2003006002A1 (en) |
ZA (1) | ZA200400210B (en) |
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US20040229960A1 (en) * | 2001-07-13 | 2004-11-18 | David Sherris | Compositions and methods of administering tubulin binding agents for the treatment of ocular diseases |
JP4005048B2 (en) * | 2003-04-09 | 2007-11-07 | 日信工業株式会社 | Carbon fiber composite material and method for producing the same |
WO2011003080A1 (en) * | 2009-07-02 | 2011-01-06 | Oxigene, Inc. | Combretastatins for prevention of posterior capsule opacification |
JP2013502440A (en) * | 2009-08-27 | 2013-01-24 | バイオノミックス リミテッド | Treatment of macular degeneration |
US9006284B2 (en) | 2009-08-27 | 2015-04-14 | Bionomics Limited | Combination therapy for treating proliferative diseases |
AP2015008241A0 (en) * | 2012-08-02 | 2015-01-31 | Amril Ag | Natural rubber containing nanocarbon |
CN113520995B (en) * | 2021-08-16 | 2023-03-10 | 海南鑫开源医药科技有限公司 | Ion-sensitive in-situ gel for eyes, and preparation method and application thereof |
CN113577020B (en) * | 2021-08-16 | 2022-09-23 | 海南鑫开源医药科技有限公司 | Vitreous intracavity injection, preparation method and application thereof |
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CA1338645C (en) * | 1987-01-06 | 1996-10-15 | George R. Pettit | Isolation, structural elucidation and synthesis of novel antineoplastic substances denominated "combretastatins" |
US5504074A (en) * | 1993-08-06 | 1996-04-02 | Children's Medical Center Corporation | Estrogenic compounds as anti-angiogenic agents |
WO1999035150A1 (en) * | 1998-01-09 | 1999-07-15 | Arizona Board Of Regents, A Body Corporate, Acting On Behalf Of Arizona State University | Synthesis of combretastatin a-4 prodrugs and trans-isomers thereo f |
GB9903404D0 (en) * | 1999-02-16 | 1999-04-07 | Angiogene Pharm Ltd | Methods of treatment and compositions useful for the treatment of diseases involving angiogenesis |
AU776511B2 (en) * | 1999-02-18 | 2004-09-09 | Baylor University | Compositions and methods for use in targeting vascular destruction |
US6670344B2 (en) * | 2000-09-14 | 2003-12-30 | Bristol-Myers Squibb Company | Combretastatin A-4 phosphate prodrug mono- and di-organic amine salts, mono- and di- amino acid salts, and mono- and di-amino acid ester salts |
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2002
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- 2002-07-15 KR KR10-2004-7000464A patent/KR20040030042A/en active Search and Examination
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- 2002-07-15 WO PCT/US2002/022449 patent/WO2003006002A1/en active Application Filing
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WO2003006002A8 (en) | 2004-05-27 |
WO2003006002A1 (en) | 2003-01-23 |
CA2453442C (en) | 2011-02-01 |
ZA200400210B (en) | 2005-06-29 |
EP1406600A4 (en) | 2007-06-06 |
EP1406600A1 (en) | 2004-04-14 |
JP2004536847A (en) | 2004-12-09 |
NZ575466A (en) | 2011-01-28 |
KR20040030042A (en) | 2004-04-08 |
CN1527704B (en) | 2011-05-18 |
CN1527704A (en) | 2004-09-08 |
WO2003006002A9 (en) | 2004-07-22 |
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