ANTI-ANGIOGENIC COMPOSITIONS AND METHODS OF USE
The present invention provides compositions comprising an anti-angiogenic factor, and a polymeric carrier. Representative examples of anti-angiogenic factors include Anti-Invasive Factor, Retinoic acids and derivatives thereof, and taxol. Also provided are methods for embolizing blood vessels, and eliminating biliary, urethral, esophageal, and tracheal/bronchial obstructions.
1 . A composition, comprising:
(a) a compound which disrupts microtubule function, and
(b) a polymeric carrier, with the proviso that said polymeric carrier is not a capsule.
2 . The composition according to claim 1 wherein said composition is formed into microspheres having an average size of between 0.5 and 200 μm.
3 . The composition according to claim 1 wherein said composition is formed into a film with a thickness of between 100 μm and 2 mm.
4 . The composition according to claim 1 wherein said composition is liquid above 45° C., and solid or semi-solid at 37° C.
5 . The composition according to claim 1 wherein said polymeric carrier is poly(ethylene-vinyl acetate) (40% crosslinked).
6 . The composition according to claim 1 wherein said polymeric carrier is copolymer of lactic acid and glycolic acid.
7 . The composition according to claim 1 wherein said polymeric carrier is poly (caprolactone).
8 . The composition according to claim 1 wherein said polymeric carrier is poly (lactic acid).
9 . The composition according to claim 1 wherein said polymeric carrier is a copolymer of poly (lactic acid) and poly (caprolactone).
10 . The composition according to claim 1 wherein said compound which disrupts microtubule function is paclitaxel.
11 . The composition according to claim 1 wherein said compound which disrupts microtubule function is selected from the group consisting of estramustine, colchicine, methotrexate, curacin-A, epothilone, vinblastine and tBCEU.
12 . A composition, comprising:
(a) an anti-angiogenic factor: and
(b) hyaluronic acid.
13 . The composition of claim 10 wherein said anti-angiogenic factor is selected from the group consisting of paclitaxel, suramin, methotrexate and lighter d group transition metals.
14 . A composition comprising:
(a) a lighter d group transition metal which inhibits the formation of new blood vessels; and
(b) a polymeric carrier.
15 . The composition according to claim 14 wherein said lighter d group is selected from the group consisting of species of vanadium, molybdenum, tungsten, titanium, niobium and tantalum.
16 . A method for embolizing a blood vessel, comprising delivering into said vessel a therapeutically effective amount of composition according to any one of claims 1 - 15 , such that said blood vessel is effectively occluded.
17 . The method according to claim 16 wherein said blood vessel nourishes a tumor.
18 . A stent, comprising a generally tubular structure, the surface of which is coated with a composition comprising an anti-angiogenic factor and a polymeric carrier.
19 . A method for expanding the lumen of a body passageway, comprising inserting a stent into the passageway, the stent having a generally tubular structure, the surface of said structure being coated with a composition comprising an anti-angiogenic factor and a polymeric carrier, such that said passageway is expanded.
20 . A method for eliminating vascular obstructions, comprising inserting a vascular stent into a vascular passageway, the stent having a generally tubular structure, the surface of said structure being coated with a composition comprising an anti-angiogenic factor and a polymeric carrier, such that said vascular obstruction is eliminated.
21 . A method for eliminating biliary obstructions, comprising inserting a biliary stent into a biliary passageway, the stent having a generally tubular structure, the surface of said structure being coated with a composition comprising an anti-angiogenic factor and a polymeric carrier, such that said biliary obstruction is eliminated.
22 . A method for eliminating urethral obstructions, comprising inserting a urethral stent into a urethra, the stent having a generally tubular structure, the surface of said structure being coated with a composition comprising an anti-angiogenic factor and a polymeric carrier, such that said urethral obstruction is eliminated.
23 . A method for eliminating esophageal obstructions, comprising inserting an esophageal stent into an esophagus, the stent having a generally tubular structure, the surface of said structure being coated with a composition comprising an anti-angiogenic factor and a polymeric carrier, such that said esophageal obstruction is eliminated.
24 . A method for eliminating tracheal/bronchial obstructions, comprising inserting a tracheal/bronchial stent into the trachea or bronchi, the stent having a generally tubular structure, the surface of which is coated with a composition comprising an anti-angiogenic factor and a polymeric carrier, such that said tracheal/bronchial obstruction is eliminated.
25 . A method for treating a tumor excision site, comprising administering a composition comprising an anti-angiogenic factor and a polymeric carrier to the resection margin of a tumor subsequent to excision, such that the local recurrence of cancer and the formation of new blood vessels at said site is inhibited.
26 . The method according to claim 25 wherein said composition is liquid above 45° C. and solid or semi-solid at 37° C.
27 . The method according to claim 26 wherein the step of administering comprises spraying microspheres composed of said composition into the resection margin of the tumor.
28 . A method for treating corneal neovascularization, comprising administering to a patient a therapeutically effective amount of a composition comprising an anti-angiogenic factor and a polymeric carrier to the cornea, such that the formation of blood vessels is inhibited.
29 . A method for treating corneal neovascularization, comprising administering to a patient a therapeutically effective amount of paclitaxel to the cornea, such that the formation of blood vessels is inhibited.
30 . The method according to claims 28 or 29 wherein said method further comprises the administration of a topical corticosteroid.
31 . A method for inhibiting angiogenesis in patients with non-tumorigenic, angiogenesis-dependent diseases, comprising administering to a patient a therapeutically effective amount of a composition comprising paclitaxel to a patient with a non-tumorigenic angiogenesis-dependent disease, such that the formation of new blood vessels is inhibited.
32 . A method for embolizing a blood vessel in a non-tumorigenic, angiogenesis-dependent diseases, comprising delivering to said vessel a therapeutically effective amount of a composition comprising paclitaxel, such that said blood vessel is effectively occluded.
33 . A method for expanding the lumen of a body passageway, comprising inserting a stent into the passageway, the stent having a generally tubular structure, the surface of said structure being coated with a composition comprising paclitaxel, such that said passageway is expanded.
34 . A method for eliminating vascular obstructions, comprising inserting a vascular stent into a vascular passageway, the stent having a generally tubular structure, the surface of said structure being coated with a composition comprising paclitaxel, such that said vascular obstruction is eliminated.
35 . A method for eliminating biliary obstructions, comprising inserting a biliary stent into a biliary passageway, the stent having a generally tubular structure, the surface of said structure being coated with a composition comprising paclitaxel, such that said biliary obstruction is eliminated.
36 . A method for eliminating urethral obstructions, comprising inserting a urethral stent into a urethra, the stent having a generally tubular structure, the surface of said structure being coated with a composition comprising paclitaxel, such that said urethral obstruction is eliminated.
37 . A method for eliminating esophageal obstructions, comprising inserting an esophageal stent into an esophagus, the stent having a generally tubular structure, the surface of said structure being coated with a composition comprising paclitaxel, such that said esophageal obstruction is eliminated.
38 . A method for eliminating tracheal/bronchial obstructions, comprising inserting a tracheal/bronchial stent into the trachea or bronchi, the stent having a generally tubular structure, the surface of said structure being coated with a composition comprising paclitaxel, such that said tracheal/bronchial obstruction is eliminated.
39 . A method for treating a tumor excision site, comprising administering to a patient a composition comprising paclitaxel to the resection margin of a tumor subsequent to excision, such that the local recurrence of cancer and the formation of new blood vessels at said site is inhibited.
40 . A method for treating neovascular disease of the eye, comprising administering to a patient a therapeutically effective amount of a compound which disrupts microtubule function to the cornea, such that the formation of new vessels is inhibited.
41 . The method according to claim 40 wherein said compound which disrupts microtubule function is paclitaxel.
42 . The method according to claim 40 wherein said compound which disrupts microtubule function is selected from the group consisting of estramustine, colchicine, methotrexate, curacin-A, epothilone, vinblastine and tBCEU.
43 . The method according to claim 40 wherein said neovascular disease is selected from the group consisting of corneal neovascularization and macular degeneration.
44 . A method for treating inflammatory arthritis, comprising administering to a patient a therapeutically effective amount of a composition comprising an anti-angiogenic factor and a polymeric carrier to a joint, such that the formation of blood vessels is inhibited, with the proviso that said anti-angiogenic factor is not methotrexate.
45 . The method according to claim 44 wherein said anti-angiogenic factor is a compound which disrupts microtubule function.
46 . The method according to claim 44 wherein said compound which disrupts microtubule function is selected from the group consisting of estramustine, colchicine, curacin-A, epothilone, vinblastine and tBCEU.
47 . The method according to claim 44 wherein said compound which disrupts microtubule function is paclitaxel.
48 . A method for inflammatory arthritis, comprising administering to a patient a therapeutically effective amount of an anti-angiogenic factor to a joint, such that the formation of blood vessels is inhibited, with the proviso that said anti-angiogenic factor is not methotrexate.
49 . The method according to claim 48 wherein said anti-angiogenic factor is a compound which disrupts microtubule function.
50 . The method according to claim 48 wherein said compound which disrupts microtubule function is selected from the group consisting of estramustine, colchicine, curacin-A, epothilone, vinblastine and tBCEU.
51 . The method according to claim 48 wherein said compound which disrupts microtubule function is paclitaxel.
52 . A composition comprising a polymeric carrier adapted to contain and release a hydrophobic compound, said carrier containing a hydrophobic compound in combination with a carbohydrate, protein or polypeptide.
53 . The composition of claim 52 wherein said polymeric carrier is poly(ethylene-vinyl acetate) (40% crosslinked).
54 . The composition of claim 52 wherein said polymeric carrier is copolymer of lactic acid and glycolic acid.
55 . The composition of claim 52 wherein said polymeric carrier is poly (caprolactone).
56 . The composition of claim 52 wherein said polymeric carrier is poly (lactic acid).
57 . The composition according to claim 52 wherein said hydrophobic compound is a compound which disrupts microtubule function.
58 . The composition according to claim 57 wherein said compound which disrupts microtubule function is paclitaxel.
59 . The composition according to claim 57 wherein said compound which disrupts microtubule function is selected from the group consisting of estramustine, colchicine, methotrexate, curacin-A, epothilone, vinblastine and tBCEU.
60 . A pharmaceutical product, comprising:
(a) a compound which disrupts microtubule function, in a container; and
(b) a notice associated with said container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by said agency of said paclitaxel, for human or veterinary administration to treat non-tumorigenic angiogenesis-dependent diseases.
61 . The pharmaceutical product according to claim 60 wherein said compound which disrupts microtubule function is paclitaxel.