US5225212A
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Microreservoir liposome composition and method
Assignee: Liposome Technology Inc
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Filing: 1990-12-10
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Granted: 1993-07-06
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Expires: 2010-12-10
Abstract
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.
Inventors
- 👤 Francis J. Martin
- 👤 Martin C. Woodle
- 👤 Carl Redemann
- 👤 Annie Yau-Young
- 👤 Ramachandran Radhakrishnan
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 01:35
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61K47/00; A61K47/50; A61K47/69; A61K47/6905; A61K47/6911; Y; Y02; Y02A; Y02A50/00; Y02A50/30
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
134 words
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.
Claim 2
Dependent Claim
134 words
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.
Claim 3
Dependent Claim
19 words
The composition of claim 1, wherein the hydrophilic polymer is polyethyleneglycol having a molecular weight between about 1,000-5,000 daltons.
Claim 4
Dependent Claim
13 words
The composition of claim 2, wherein the polymer is derivatized to a phospholipid.
Claim 5
Dependent Claim
20 words
The composition of claim 1, wherein the polymer is selected from the group consisting of polyacetic acid and polyglycolic acid.
Claim 6
Dependent Claim
143 words
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.
Claim 7
Dependent Claim
143 words
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.
Claim 8
Dependent Claim
19 words
The composition of claim 5, wherein the hydrophilic polymer is polyethyleneglycol having a molecular weight between about 1,000-5,000 daltons.
Claim 9
Dependent Claim
53 words
The composition of claim 5, wherein the polypeptide is a peptide hormone which is therapeutically active at a plasma concentration in the picogram/ml range, and the liposome composition is effective to release the hormone in a therapeutically effective dose for a period of at least five days after intravenous administration of the composition.
Claim 10
Dependent Claim
11 words
The composition of claim 7, wherein the peptide hormone is vasopressin.
Claim 11
Dependent Claim
88 words
The composition of claim 5, wherein the compound is a protein selected from the group consisting of superoxide dismutase, glucocerebrosidase, asparaginase, adenosine deaminase, interferons (alpha, beta, and gamma), interleukin (1,2,3,4,5,6,7), tissue necroses factor (TNF-alpha, beta), colony stimulating factors (-CSF (macrophage), G-CSF (granulocyte), GM-CSF (granulocyte, macrophage), TPA, prourokinase, and urokinase, HIV-1 vaccine, hepatitis B vaccine, malaria vaccine, and melanoma vaccine, erythropoietin (EPO), factor VIII, bone growth factor, fibroblast growth factor, nerve growth factor, platelet-derived growth factor, tumor growth factors (alpha, beta), somatomedin C (IGF-1), and a ribosome inhibitor protein.
Claim 12
Dependent Claim
13 words
The composition of claim 9, wherein the protein is macrophage colony stimulating factor.
Claim 13
Independent Claim
139 words
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.
Claim 14
Independent Claim
139 words
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.
Claim 15
Dependent Claim
19 words
The method of claim 11, wherein the hydrophilic polymer is polyethyleneglycol having a molecular weight between about 1,000-5,000 daltons.
Claim 16
Dependent Claim
20 words
The method of claim 11, wherein the polymer is selected from the group consisting of polylactic acid and polyglycolic acid.
Claim 17
Dependent Claim
46 words
The method of claim 11, wherein the compound is a peptide hormone which is therapeutically active at a plasma concentration in the picogram-to-nanogram/ml range, and said administering is effective to release the hormone in a therapeutically effective dose for a period of at least five days.
Claim 18
Dependent Claim
11 words
The method of claim 14, wherein the peptide hormone is vasopressin.
Claim 19
Dependent Claim
82 words
The method of claim 11, wherein the compound is a protein selected from the group consisting of superoxide dismutase, glucocerebrosidase, asparaginase, adenosine deaminase, interferons (alpha, beta, and gamma), interleukin (1,2,3,4,5,6,7), tissue necroses factor (TNF - alpha, beta), colony stimulating factors (M-CSF (macrophage), G-CSF (granulocyte), GM-CSF (granulocyte, macrophage), TPA, prourokinase, and urokinase, HIV-1 vaccine, erythropoietin (EPO), factor VIII, bone growth factor, fibroblast growth factor, nerve growth factor, platelet-derived growth factor, tumor growth factors (alpha, beta), somatomedin C (IGF-1), and a ribosome inhibitor protein.
Claim 20
Dependent Claim
13 words
The method of claim 16, wherein the protein is macrophage colony stimulating factor.
Claim 21
Dependent Claim
116 words
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.
Claim 22
Dependent Claim
116 words
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.
Claim 23
Dependent Claim
90 words
The composition of claim 18, wherein the compound is a polypeptide selected from the group consisting of superoxide dismutase, glucocerebrosidase, asparaginase, adenosine deaminase, interferons (alpha, beta, and gamma), interleukin (1,2,3,4,5,6,7), tissue necrosis factor (TNF - alpha, beta), colony stimulating factors (M-CSF (macrophage), G-CSF (granulocyte), GM-CSF (granulocyte, macrophage), TPA, prourokinase, and urokinase, HIV-1 vaccine, hepatitis B vaccine, malaria vaccine, and melanoma vaccine, erythropoietin (EPO), factor VIII, bone growth factor, fibroblast growth factor, nerve growth factor, platelet-derived growth factor, tumor growth factors (alpha, beta), somatomedin C (IGF-1), and a ribosome inhibitor protein.
Claim 24
Dependent Claim
10 words
The composition of claim 19, wherein the polypeptide is vasopressin.
Claim 25
Independent Claim
125 words
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.
Claim 26
Independent Claim
125 words
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.
Claim 27
Dependent Claim
89 words
The method of claim 21, wherein the compound is a peptide hormone selected from the group consisting of superoxide dismutase, glucocerebrosidase, asparaginase, adenosine deaminase, interferons (alpha, beta, and gamma), interleukin (1,2,3,4,5,6,7), tissue necroses factor (TNF-alpha, beta), colony stimulating factors (M-CSF (macrophage), G-CSF (granulocyte), GM-CSF (granulocyte, macrophage), TPA, prourokinase, and urokinase, HIV-1 vaccine, hepatitis B vaccine, malaria vaccine, and melanoma vaccine, erythropoietin (EPO), factor VIII, bone growth factor, fibroblast growth factor, nerve growth factor, platelet-derived growth factor, tumor growth factors (alpha, beta), somatomedin C (IGF-1), and a ribosome inhibitor protein.
Claim 28
Dependent Claim
10 words
The method of claim 22, wherein the polypeptide is vasopressin.
Claim 29
Dependent Claim
27 words
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.
Claim 30
Dependent Claim
27 words
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.
Claim 31
Dependent Claim
23 words
A lipid composition composed of a vesicle-forming lipid having a polar head group, and a polylactic acid moiety derivatized to said head group.
Claim 32
Dependent Claim
23 words
A lipid composition composed of a vesicle-forming lipid having a polar head group, and a polylactic acid moiety derivatized to said head group.
Claim 33
Dependent Claim
23 words
A lipid composition composed of a vesicle-forming lipid having a polar head group, and a polyglycolic acid moiety derivatized to said head group.
Claim 34
Dependent Claim
23 words
A lipid composition composed of a vesicle-forming lipid having a polar head group, and a polyglycolic acid moiety derivatized to said head group.
References Cited (Backward Citations)
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