Reduction of intravenously administered nanoparticulate-formulation-induced adverse physiological reactions
First Claim
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1. A method of administering a nanoparticulate composition to a mammal without eliciting adverse hemodynamic effects comprising intravenously administering to said mammal an effective amount of a nanoparticulate drug composition at an infusion rate not exceeding a solids dose rate of less than 10 mg/min, wherein said drug composition comprises:
- (a) particles consisting essentially of from about 0.1 to about 99.9% by weight of a crystalline organic drug substance having a solubility in water of less than 10 mg/ml;
(b) a surface modifier adsorbed on the surface of the drug substance in an amount of from about 0.1 to about 99.9% by weight and sufficient to maintain an effective average particle size of from about 50 nm to about 1000 nm; and
(c) a pharmaceutically acceptable carrier therefor.
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Abstract
Disclosed are methods of intravenous administration of nanoparticulate drug formulations to a mammal to avoid adverse hemodynamic effects: by reducing the rate and concentration of the nanoparticles in the formulations; or by pre-treating the subject with histamine; or by pretreating the subject with a desensitizing amount of the nanoparticulate drug formulations.
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Citations
35 Claims
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1. A method of administering a nanoparticulate composition to a mammal without eliciting adverse hemodynamic effects comprising intravenously administering to said mammal an effective amount of a nanoparticulate drug composition at an infusion rate not exceeding a solids dose rate of less than 10 mg/min, wherein said drug composition comprises:
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(a) particles consisting essentially of from about 0.1 to about 99.9% by weight of a crystalline organic drug substance having a solubility in water of less than 10 mg/ml;
(b) a surface modifier adsorbed on the surface of the drug substance in an amount of from about 0.1 to about 99.9% by weight and sufficient to maintain an effective average particle size of from about 50 nm to about 1000 nm; and
(c) a pharmaceutically acceptable carrier therefor. - View Dependent Claims (2, 3, 4, 23, 26, 31)
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5. A method of administering a nanoparticulate composition to a mammal without eliciting adverse hemodynamic effects comprising:
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(a) intravenously administering to said mammal an antihistamine in the amount of from about 5 to about 10 mg/kg of body weight; and
(b) subsequently intravenously administering to said mammal an effective amount of a nanoparticulate drug composition comprising;
(1) particles consisting essentially of from about 0.1 to about 99.9% by weight of a crystalline drug substance having a solubility in water of less than 10 mg/ml; and
(b 2) a surface modifier adsorbed on the surface of the drug substance in an amount of from about 99.9 to about 0.1% by weight and sufficient to maintain an effective average particle size of less than about 1000 nm. - View Dependent Claims (6, 7, 8, 27, 32)
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9. A method of administering a nanoparticulate composition to a mammal without eliciting adverse hemodynamic effects comprising:
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(a) intravenously administering to said mammal a desensitizing amount of a nanoparticulate drug composition at an infusion rate not exceeding a solids dose rate of less than 10 mg/min; and
(b) intravenously administering an effective amount of said nanoparticulate composition comprising;
(1) particles consisting essentially of from about 0.1 to about 99.9% by weight of a crystalline organic drug substance having a solubility in water of less than 10 mg/ml;
(2) a surface modifier adsorbed on the surface of the drug substance in an amount sufficient to maintain an effective average particle size of from about 100 to about 1000 nm; and
(3) a pharmaceutically acceptable carrier therefor. - View Dependent Claims (10, 11, 12, 24, 28, 33)
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13. A method of administering a nanoparticulate composition to a mammal without eliciting adverse hemodynamic effects comprising intravenously administering to said mammal an effective amount of a nanoparticulate drug composition at an infusion rate not exceeding a solids dose rate of less than 10 mg/min, wherein said drug composition comprises:
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(a) particles having an effective average particle size of from about 50 to about 1000 nm and consisting essentially of from about 0.1 to about 99.9% by weight of an organic drug substance entrapped in from about 99.9 to about 0.1% by weight of liposome or a colloidal polymeric material; and
(b) a pharmaceutically acceptable carrier therefor. - View Dependent Claims (14, 15, 16, 21, 25, 29, 34)
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17. A method of administering a nanoparticulate composition to a mammal without eliciting adverse hemodynamic effects comprising:
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(a) intravenously administering to said mammal an antihistamine in the amount of from about 5 to about 10 mg/kg of body weight; and
(b) subsequently intravenously administering to said mammal an effective amount of a nanoparticulate drug composition comprising;
(1) particles having an effective average particle size of from about 50 to bout about 1000 nm and consisting essentially of from about 0.1 to about 99.9% by weight of an organic drug substance entrapped in from about 99.9 to about 0.1% by weight of liposome or a colloidal polymeric material; and
(2) a pharmaceutically acceptable carrier therefor. - View Dependent Claims (18, 19, 20, 22, 30, 35)
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Specification