Patent US4873088A successfully refreshed from Google Patents.
US4873088A
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US
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Liposome drug delivery method and composition
Assignee: Liposome Technology Inc
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Filing: 1987-07-13
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Granted: 1989-10-10
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Expires: 2007-07-13
Abstract
Abstract A method for enhancing the therapeutic effectiveness of adriamycin, in the treatment of cancer, is disclosed. Liposomes containing coentrapped adriamycin and a secondary compound effective to reduce the toxicity of adriamycin or enhance the induction by adriamycin of the tumoricidal activity of host lymphoid cells, such as lipopolysaccharide, are administered parenterally in a therapeutically effective dose. In another aspect, macrophages stimulated in vivo with liposomes containing entrapped liposomes are exposed to an immunostimulator, for enhanced tumoricidal activity. Also disclosed are liposome compositions containing coentrapped adriamycin and an immunostimulator.
Inventors
- 👤 Eric Mayhew
- 👤 M. Jane Ehrke
- 👤 Kenneth Mace
- 👤 Francis Szoka
- 👤 Fred C. Olson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 01:44
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61K9/1272
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
73 words
In the treatment of cancerous tumors in a mammal in need of such treatment, a method for enhancing the therapeutic effectiveness of adriamycin and a secondary compound capable of: (a) reducing adriamycin toxicity; or (b) enhancing the induction of host defenses by adriamycin, when administered in free form, comprising providing a suspension of lipid bilayer vesicles containing co-entrapped adriamycin and the secondary compound, and administering a therapeutically effective amount of the suspension parenterally.
Claim 2
Dependent Claim
73 words
In the treatment of cancerous tumors in a mammal in need of such treatment, a method for enhancing the therapeutic effectiveness of adriamycin and a secondary compound capable of: (a) reducing adriamycin toxicity; or (b) enhancing the induction of host defenses by adriamycin, when administered in free form, comprising providing a suspension of lipid bilayer vesicles containing co-entrapped adriamycin and the secondary compound, and administering a therapeutically effective amount of the suspension parenterally.
Claim 3
Dependent Claim
52 words
The method of claim 1, wherein the secondary compound acts to reduce the toxicity of adriamycin, and is selected from the group consisting of alpha-tocopherol, including analogues thereof, including alpha-tocopherol succinate, provided that if the secondary compound is alpha-tocopherol, the toxicity for adriamycin is reduced at least three and a half times.
Claim 4
Dependent Claim
50 words
The method of claim 2, wherein the compound includes alpha-tocopherol, and the toxicity of the drug entrapped in lipid vesicles also containing alpha-tocopherol, as measured in mice, is decreased at least about 50% below the toxicity of the same amount of adriamycin administered in liposomes which do not contain alpha-tocopherol.
Claim 5
Dependent Claim
23 words
The method of claim 2, wherein the liposomes also contain a secondary compound capable of enhancing the induction of host defenses by adriamycin.
Claim 6
Dependent Claim
22 words
The method of claim 1 wherein the secondary compound is an immunostimulator which potentiates the induction of tumoricidal activity in lymphoid cells.
Claim 7
Dependent Claim
24 words
The method of claim 5, wherein the immunostimulator is selected from the group consisting of lipopolysaccharides obtained from the cell walls of gram-negative bacteria.
Claim 8
Dependent Claim
24 words
The method of claim 6, for use in treating ovarian tumors, wherein the liposomes are administered by intraperitoneal injection, in a therapeutically effective amount.
Claim 9
Dependent Claim
35 words
A liposome composition for treating cancerous tumors in a mammal in need of such treatment comprising liposomes containing adriamycin and an immunostimulator effective to enhance the induction of host defenses in lymphoid cells by adriamycin.
Claim 10
Dependent Claim
35 words
A liposome composition for treating cancerous tumors in a mammal in need of such treatment comprising liposomes containing adriamycin and an immunostimulator effective to enhance the induction of host defenses in lymphoid cells by adriamycin.
Claim 11
Dependent Claim
21 words
The composition of claim 8, wherein the composition is an aqueous suspension containing adriamycin and macrophage stimulator predominantly in liposome-entrapped form.
Claim 12
Dependent Claim
25 words
The composition of claim 8, wherein the macrophage stimulator is selected from the group consisting of lipopolysaccharides obtained from the cell walls of gram-negative bacteria.
Claim 13
Dependent Claim
42 words
The composition of claim 10, wherein the liposomes also contain a secondary compound which acts to reduce the toxicity of adriamycin, and is selected from the group consisting of N-acetylcysteine, niacin, isocitrate, hydroxybutylated toluene, and alpha-tocopherol, and analogues thereof, including alpha-tocopherol succinate.
Claim 14
Independent Claim
47 words
A method of enhancing the tumoricidal activity of macrophages, as evidenced by the ability of isolated macrophages to lyse mastocytoma cells in culture, comprising administering in vivo a suspension of liposomes with entrapped adriamycin, and exposing the macrophages from the subject receiving the suspension to an immunostimulator.
Claim 15
Independent Claim
47 words
A method of enhancing the tumoricidal activity of macrophages, as evidenced by the ability of isolated macrophages to lyse mastocytoma cells in culture, comprising administering in vivo a suspension of liposomes with entrapped adriamycin, and exposing the macrophages from the subject receiving the suspension to an immunostimulator.
Claim 16
Dependent Claim
19 words
The method of claim 12, wherein the immunostimulator is a lipopolysaccharide obtained from the cell walls of gram-negative bacteria.
Claim 17
Dependent Claim
25 words
The method of claim 12, wherein the microphages are exposed to the stimulator in vitro and which further includes introducing the stimulated macrophages in vivo.
Claim 18
Dependent Claim
25 words
The method of claim 12, wherein the adriamycin-containing liposomes are administered by intraperitoneal injection, in a liposome suspension containing a pharmacologically effective amount of adriamycin.
Claim 19
Dependent Claim
34 words
The method of claim 15, for use in treating ovarian cancer, wherein said exposing includes administering a pharmaceutically effective amount of macrophage stimulator within a period up to about 18 days after said administering.
Claim 20
Dependent Claim
16 words
The method of claim 16, wherein the adriamycin and immunostimulator are coentrapped in the same liposomes.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-10-09 | 1993-04-10 | 1993-10-10 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-10-09 | 1997-04-10 | 1997-10-10 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-10-09 | 2001-04-10 | 2001-10-10 | $7700.00 | Window Closed / Lapsed |