Microreservoir liposome composition and method
First Claim
1. A liposome composition effective to extend, to at least 24 hours, the period of effective activity of a therapeutic compound which can be administered intravenously in a therapeutically effective amount and which is cleared in free form from the bloodstream with a halflife of less than about 4 hours, comprisingliposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivatized with a polymer selected from the group consisting of polyethyleneglycol, polyacetic acid and polyglycolic acid, and (ii) having a selected mean particle diameter in the size range between about 0.1 to 0.4 microns, andthe compound in liposome-entrapped form,for intravenous administration at a dose of the composition which contains an amount of the compound in liposome-entrapped form which is at least three times such therapeutically effective amount.
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Abstract
A liposome composition for extended release of a therapeutic compound into the bloodstream. The liposomes are composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivatized with hydrophilic polymer, have sizes in a selected size range between 0.1 and 0.4 microns, and contain the therapeutic compound in liposome-entrapped form. The dosage form of the composition contains at least about three times the dose of the compound required for intravenous injection in free form. Also disclosed in a method for extending to at least 24 hours the period in which an intravenously administered therapeutic compound is therapeutically active in the bloodstream, and novel liposomes compositions for practicing the method.
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Citations
26 Claims
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1. A liposome composition effective to extend, to at least 24 hours, the period of effective activity of a therapeutic compound which can be administered intravenously in a therapeutically effective amount and which is cleared in free form from the bloodstream with a halflife of less than about 4 hours, comprising
liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivatized with a polymer selected from the group consisting of polyethyleneglycol, polyacetic acid and polyglycolic acid, and (ii) having a selected mean particle diameter in the size range between about 0.1 to 0.4 microns, and the compound in liposome-entrapped form, for intravenous administration at a dose of the composition which contains an amount of the compound in liposome-entrapped form which is at least three times such therapeutically effective amount.
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5. A liposome composition effective to extend, to at least 48 hours, the period of therapeutic activity of a polypeptide which can be administered intravenously in a therapeutically effective amount, which is cleared in free form from the bloodstream with a halflife of less than about 4 hours, and whose therapeutically active blood concentration is in the picogram-nanogram/ml concentration range, comprising
liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivitized with a polymer selected from the group consisting of polyethyleneglycol, polyacetic acid and polyglycolic acid, and (ii) having a selected mean particle diameter in the size range between about 0.1 to 0.4 microns, and the polypeptide in liposome-entrapped form, for intravenous administration at a dose of the composition which contains an amount of the polypeptide liposome-entrapped form which is at least three times such therapeutically effective amount.
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11. A method of extending, to at least 24 hours, the period of effective activity of a therapeutic compound which can be administered intravenously in a therapeutically effective amount, and which has a halflife in the bloodstream in free form of less than about 4 hours, comprising
providing a liposome composition containing liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivitized with ah polymer selected from the group consisting of polyethyleneglycol, polyacetic acid and polyglycolic acid, and (ii) having a selected mean particle diameter in the size range between about 0.1 to 0.4 microns, and the compound at least about 70% in liposome-entrapped form, and administering the liposome composition intravenously to a subject at a dose which contains an amount of the compound which is at least three times such therapeutically effective amount.
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18. A liposome composition effective to extend, to at least one week, the period of effective activity of a therapeutic compound which can be administered in a therapeutically effective amount, comprising
liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivitized with a polymer selected from the group consisting of polyethyleneglycol, polyacetic acid and polyglycolic acid, and (ii) having a selected mean particle diameter in the size range between about 0.1 to 0.4 microns, and the compound in liposome-entrapped form, for subcutaneous administration at a dose of the composition which contains an amount of the compound in liposome-entrapped form which is at least ten times such therapeutically effective intravenously administered amount.
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21. A method of extending, to at least one week, the period of effective activity of a therapeutic compound which can be administered in a therapeutically effective amount, comprising
providing a liposome composition containing liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivitized with a polymer selected from the group consisting of polyethyleneglycol, polyacetic acid and polyglycolic acid, and (ii) having a selected mean particle diameter in the size range between about 0.1 to 0.4 microns, and the compound at least about 70% in liposome-entrapped form, and administering the composition subcutaneously to a subject at a dose which contains an amount of the compound in liposome-entrapped form which is at least ten times such therapeutically effective intravenously administered amount.
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24. A liposome composition composed of vesicle-forming lipids and a vesicle-forming lipid derivatized with a hydrophilic polymer selected from the group consisting of polylactic acid and polyglycolic acid.
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25. A lipid composition composed of a vesicle-forming lipid having a polar head group, and a polylactic acid moiety derivatized to said head group.
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26. A lipid composition composed of a vesicle-forming lipid having a polar head group, and a polyglycolic acid moiety derivatized to said head group.
Specification