US2008166387A1PendingUtilityA1

Anti-angiogenic compositions and methods of use

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Assignee: HUNTER WILLIAM LPriority: Jul 19, 1993Filed: Jul 30, 2007Published: Jul 10, 2008
Est. expiryJul 19, 2013(expired)· nominal 20-yr term from priority
Inventors:William L. HunterLindsay MachanA. ArsenaultHelen BurtJohn JacksonStephen Dordunoo
A61P 7/04A61P 43/00A61P 7/02A61P 35/00A61P 9/10A61P 9/00A61P 9/14A61P 27/02A61P 1/16A61P 19/02A61P 11/00A61P 13/02A61P 1/04A61K 31/555A61L 2300/622A61K 9/14A61K 45/06A61L 2300/606A61L 31/10A61K 38/57A61K 33/30A61K 31/525A61K 33/00A61K 31/565A61K 31/136C08L 2203/02A61L 2300/416A61L 31/145A61K 9/1635A61K 31/426A61K 31/122A61K 31/702Y10S977/773A61K 9/1647A61K 9/0051B82Y 5/00C08L 23/0853A61K 9/7007Y10S977/915A61K 31/203A61K 9/0019A61K 33/06A61K 31/519A61K 31/335A61K 31/337A61K 9/0048C08L 29/04A61L 2430/36A61L 31/16C07C 233/64C07K 14/811A61K 9/5031C08L 67/04A61K 9/5153A61K 9/1641A61K 9/1658C08L 2312/00A61K 31/57A61K 31/185A61K 31/4745A61K 31/165A61K 31/427A61K 9/5146A61K 31/20A61K 33/24
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Claims

Abstract

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.

Claims

exact text as granted — not AI-modified
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.

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