TRANSFORMATION OF DRUG CYCLODEXTRIN COMPLEX COMPOSITIONS INTO COMPOSITIONS OF MIXTURES OF LIPID VESICLE ENCAPSULATED DRUG AND CYCLODEXTRIN DRUG COMPLEXES
First Claim
1. A pharmaceutical formulation of a sparingly water-soluble therapeutic agent, said formulation comprising:
- (a) a pharmaceutically acceptable diluent;
(b) a complex between said sparingly water-soluble therapeutic agent and a solubility enhancing agent dissolved in said diluent; and
(c) a population of liposomal lipid vesicles suspended in said diluent, wherein said lipid vesicles comprise a lipid membrane encapsulating an internal aqueous medium comprising a first fraction of said sparingly water-soluble therapeutic agent, which is not complexed with a solubility enhancing agent.
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Abstract
Sparingly water-soluble agents can be formulated as cyclodextrin complexes, however, these water-soluble drug-cyclodextrin complexes dissociate when the complex is administered into patients. The dilution of the complex in the patient leads to the drug being released from the complex, so the drug is not effectively targeted. In contrast, drugs encapsulated in the aqueous core of a lipid vesicles are not released when the liposome is diluted in blood. This invention describes compositions and methods whereby cyclodextrin or polyanionic beta-cyclodextrin drug-complexes are mixed with a preformed liposome containing the amine salts of an acidic compound. This results in the drug cyclodextrin complex being transferred into the liposome where it is stably retained. The liposome-encapsulated drug can then be injected into a patient.
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Citations
24 Claims
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1. A pharmaceutical formulation of a sparingly water-soluble therapeutic agent, said formulation comprising:
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(a) a pharmaceutically acceptable diluent; (b) a complex between said sparingly water-soluble therapeutic agent and a solubility enhancing agent dissolved in said diluent; and (c) a population of liposomal lipid vesicles suspended in said diluent, wherein said lipid vesicles comprise a lipid membrane encapsulating an internal aqueous medium comprising a first fraction of said sparingly water-soluble therapeutic agent, which is not complexed with a solubility enhancing agent. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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23. A kit comprising:
- a vessel containing a cyclodextrin complexed sparingly water-soluble therapeutic agent;
a vessel containing a liposome suspension with an ion gradient such that the ion concentration is higher inside of said liposome than outside said liposome;
a vessel of a buffer; and
instructions for preparing said pharmaceutical formulation. - View Dependent Claims (24)
- a vessel containing a cyclodextrin complexed sparingly water-soluble therapeutic agent;
Specification