Thrombolytic agents and methods of treatment for thrombosis
First Claim
1. A method of treating thrombosis in animals comprising the steps of:
- introducing a pharmaceutical composition to a thrombus site by intravenous injection, said pharmaceutical composition comprising a plurality of gas filled microbubbles with a diameter of from about 0.1 to 10 microns and a pharmaceutically acceptable carrier, and thereafter;
applying ultrasound to said site.
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Abstract
The foregoing invention relates to a new microbubble preparation and thrombolytic therapy which relies on microbubbles and ultrasound for its lytic activity. The pharmaceutical composition of the invention comprises a liquid solution of microbubbles with an internal atmosphere enhanced with the perfluorocarbon gas which cavitate in the presence of an ultrasound field following intravenous injection or infusion of said composition into said host. For thrombolysis the area of a thrombus is exposed to an ultrasound field in the presence of the microbubbles and significant lysis is experienced. The method and pharmaceutical composition of the invention exhibit thrombolytic properties similar to those of other thrombolytic agents such as urokinase and are less toxic and are clot specific in that they do not introduce a systemic lytic state to a said animal.
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Citations
24 Claims
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1. A method of treating thrombosis in animals comprising the steps of:
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introducing a pharmaceutical composition to a thrombus site by intravenous injection, said pharmaceutical composition comprising a plurality of gas filled microbubbles with a diameter of from about 0.1 to 10 microns and a pharmaceutically acceptable carrier, and thereafter;
applying ultrasound to said site. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
mixing an aqueous solution comprising 2% to about 10% by weight of human serum albumin diluted about two fold to about eight fold with 5% to 50% by weight dextrose; and
exposing said solution to a sonication horn to generate stable microbubbles from about 0.1 to 10 microns in diameter, to create said pharmaceutical composition.
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10. The method of claim 9 wherein said dilution of albumin with dextrose is a 3-fold dilution.
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11. The method of claim 9 wherein said human serum albumin is a 5% by weight solution.
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12. The method of claim 9 wherein said dextrose is a 5% by weight solution.
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13. A method for treating thrombosis in animals comprising:
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(a) obtaining a pharmaceutical composition which consists essentially of;
a solution of microbubbles approximately 0.1 to 10 microns in diameter, and a pharmaceutically acceptable carrier;
(b) introducing said pharmaceutical composition to said thrombus; and
(c) exposing said pharmaceutical composition and said thrombus to an ultrasound field for a time sufficient to lyse said thrombus. - View Dependent Claims (14, 15, 16, 17, 18, 19, 20, 21, 22, 23)
mixing an aqueous solution comprising 2% to about 10% by weight of human serum albumin diluted about two fold to about eight fold with 5% to 50% by weight dextrose; and
exposing said solution to a sonication horn to create cavitation at particulate sites in said solution generating stable microspheres from about 0.1 to 10 microns in diameter, to form said pharmaceutical composition.
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21. The method of claim 20 wherein said dilution of albumin with dextrose is a 3-fold dilution.
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22. The method of claim 20 wherein said human serum albumin is a 5% by weight solution.
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23. The method of claim 20 wherein said dextrose is a 5% by weight solution.
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24. A method for lysing a thrombus in an animal comprising:
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introducing a pharmaceutical composition to said animal by intravenous injection near the site of the thrombus, said pharmaceutical composition comprising a microbubble ultrasound contrast agent, and thereafter;
applying ultrasound to said site.
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Specification