Patent US4999344A successfully refreshed from Google Patents.
US4999344A
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Phosphatidyl treatment of rapidly proliferating cells
Assignee: United States Department of the Army
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Filing: 1988-03-14
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Granted: 1991-03-12
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Expires: 2008-03-14
Abstract
Abstract Diacyl phosphatides having a polyunsaturated carboxylic acid at the 2 position are found to have cytotoxic effect against tumor cells. Subject compositions may be employed in vivo or in vitro for inhibiting tumor cell growth, either by themselves or in combination with other cytotoxic drugs. The compositions may be administered as liposomes.
Inventors
- 👤 Marti Jett-Tilton
- 👤 Carl R. Alving
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 09:08
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/66; A61K31/683; A61K31/685; A61K9/00; A61K9/10; A61K9/127
Claims Analysis
Total Claims: 52
Claim 1
Independent Claim
72 words
A method for inhibiting the proliferation of rapidly proliferating abnormal mammalian cells, said method comprising: contacting said cells with a cell proliferating inhibiting amount of a diacyl phosphatide, wherein the sn2-acyl group is a polyunsaturated fatty acid, said contacting being in the substantial absence of non-phosphatidic fatty acid esters having fewer than 2 olefinic sites of unsaturation in the fatty acid of said ester, for a sufficient time to inhibit said proliferation.
Claim 2
Independent Claim
72 words
A method for inhibiting the proliferation of rapidly proliferating abnormal mammalian cells, said method comprising: contacting said cells with a cell proliferating inhibiting amount of a diacyl phosphatide, wherein the sn2-acyl group is a polyunsaturated fatty acid, said contacting being in the substantial absence of non-phosphatidic fatty acid esters having fewer than 2 olefinic sites of unsaturation in the fatty acid of said ester, for a sufficient time to inhibit said proliferation.
Claim 3
Dependent Claim
17 words
A method according to claim 1, wherein said phosphatide is contacted in the form of a liposome.
Claim 4
Dependent Claim
11 words
A method according to claim 2, wherein said liposome comprises cholesterol.
Claim 5
Dependent Claim
12 words
A method according to claim 1, wherein said sn2-acyl group is linoleoyl.
Claim 6
Dependent Claim
11 words
A method according to claim 4, wherein said diacyl is dilinoleoyl.
Claim 7
Dependent Claim
12 words
A method according to claim 1, wherein said sn2-acyl group is arachidonyl.
Claim 8
Dependent Claim
12 words
A method according to claim 1, wherein said cells are tumor cells.
Claim 9
Dependent Claim
15 words
A method according to claim 7, wherein said tumor cells are of the mdr phenotype.
Claim 10
Independent Claim
72 words
A method for inhibiting the proliferation of neoplastic mammalian cells, said method comprising: contacting said cells with a cell proliferating inhibiting amount of a plant diacyl phosphatide composition, wherein the sn2-acyl group is a polyunsaturated fatty acid, said contacting being in the substantial absence of non-phosphatidic fatty acid esters having fewer than 2 olefinic sites of unsaturation in the fatty acid of said ester, for a sufficient time to inhibit said proliferation.
Claim 11
Independent Claim
72 words
A method for inhibiting the proliferation of neoplastic mammalian cells, said method comprising: contacting said cells with a cell proliferating inhibiting amount of a plant diacyl phosphatide composition, wherein the sn2-acyl group is a polyunsaturated fatty acid, said contacting being in the substantial absence of non-phosphatidic fatty acid esters having fewer than 2 olefinic sites of unsaturation in the fatty acid of said ester, for a sufficient time to inhibit said proliferation.
Claim 12
Dependent Claim
15 words
A method according to claim 9, wherein said plant composition is a purified soybean composition.
Claim 13
Dependent Claim
25 words
A liposome composition consisting essentially of a purified plant phosphatide composition and optionally cholesterol in a tumor cell inhibiting amount in a pharmacologically acceptable carrier.
Claim 14
Dependent Claim
25 words
A liposome composition consisting essentially of a purified plant phosphatide composition and optionally cholesterol in a tumor cell inhibiting amount in a pharmacologically acceptable carrier.
Claim 15
Dependent Claim
31 words
A liposome composition consisting essentially of a synthetic phosphatide having a polyunsaturated fatty acid at the sn2-position and optionally cholesterol in a tumor cell inhibiting amount in a pharmacologically acceptable carrier.
Claim 16
Dependent Claim
31 words
A liposome composition consisting essentially of a synthetic phosphatide having a polyunsaturated fatty acid at the sn2-position and optionally cholesterol in a tumor cell inhibiting amount in a pharmacologically acceptable carrier.
Claim 17
Dependent Claim
13 words
A liposome composition according to claim 12, wherein said phosphatide is an inositide.
Claim 18
Dependent Claim
13 words
A liposome composition according to claim 12, wherein said phosphatide is a choline.
Claim 19
Dependent Claim
47 words
The method of claim 1 wherein the lipid consist essentially of a phosphatide having the formula ##STR2## wherein R 1 and R 2 are aliphatic hydrocarbons and R 3 is a ##STR3## --O--CH 2 --CH 2 .sup.⊕ NH 3 (ethanolamine), or --O--CH 2 CHOH--CH 2 OH (glycerol).
Claim 20
Dependent Claim
12 words
The method of claim 15 wherein cholesterol is present with the phosphatide.
Claim 21
Dependent Claim
20 words
A method of claim 15 wherein the lipids present in the lipid mixture are a phosphatide and free fatty acid.
Claim 22
Dependent Claim
15 words
The method of claim 15 wherein R 2 is a fatty acid having unsaturated bonds.
Claim 23
Dependent Claim
22 words
The method of claim 18 wherein R 2 is --(CH 2 ) 7 --CH═CHCH 2 CH═CH(CH 2 ) 4 CH 3 .
Claim 24
Dependent Claim
24 words
The method of claim 18 wherein R 2 is --CH 2 CH 2 (CH 2 CH═CH) 4 (CH 2 ) 4 CH 3 .
Claim 25
Dependent Claim
32 words
The method of claim 1 wherein said cells are selected from the group comprising mammary carcinoma, lymphoid, neuroblastoma, glioblastoma, small cell lung carcinoma, lung carcinoma, melanoma, ascites, ovarian carcinoma, and bladder carcinoma.
Claim 26
Dependent Claim
14 words
The method of claim 8 wherein the tumor cell infection is a mammary carcinoma.
Claim 27
Dependent Claim
19 words
The method of claim 9 wherein the type of mammary carcinoma is MCF-7-KC control or MCF-7-KC-ADR drug resistant cells.
Claim 28
Dependent Claim
14 words
The method of claim 21 wherein the tumor cell infection is of lymphoid origin.
Claim 29
Dependent Claim
25 words
The method of claim 24 wherein the type of lymphoid cell infection is selected from the group comprising promeylocytic leukemia (HL-60) and Raji (burkitt lymphoma).
Claim 30
Dependent Claim
13 words
The method of claim 21 wherein the tumor cell infection is a neuroblastoma.
Claim 31
Dependent Claim
14 words
The method of claim 26 wherein the type of neuroblastoma is human neuroblastoma (SK-N-MC).
Claim 32
Dependent Claim
13 words
The method of claim 27 wherein the tumor cell infection is a glioblastoma.
Claim 33
Dependent Claim
12 words
The method of claim 28 wherein the type of glioblastoma is U87MG.
Claim 34
Dependent Claim
16 words
The method of claim 21 wherein the tumor cell infection is a small cell lung carcinoma.
Claim 35
Dependent Claim
15 words
The method of claim 30 wherein the type of small cell lung carcinoma is NCI-H49.
Claim 36
Dependent Claim
15 words
The method of claim 30 wherein the type of small cell lung carcinoma is NCI-H128.
Claim 37
Dependent Claim
14 words
The method of claim 21 wherein the tumor cell infection is a lung carcinoma.
Claim 38
Dependent Claim
13 words
The method of claim 33 wherein the type of lung carcinoma is SK-MES-1.
Claim 39
Dependent Claim
13 words
The method of claim 21 wherein the tumor cell infection is a melanoma.
Claim 40
Dependent Claim
12 words
The method of claim 35 wherein the type of melanoma is HT-144.
Claim 41
Dependent Claim
13 words
The method of claim 21 wherein the tumor cell infection is an ascites.
Claim 42
Dependent Claim
16 words
The method of claim 37 wherein the type of ascities is Strain E (Ehrlich-Lettre Ascites carcinoma).
Claim 43
Dependent Claim
14 words
The method of claim 21 wherein the tumor cell infection is an ovarian carcinoma.
Claim 44
Dependent Claim
14 words
The method of claim 38 wherein the type of ovarian carcinoma is OVCAR 3.
Claim 45
Dependent Claim
25 words
The method of claim 1 wherein the treatment to the cell is effected prior to transplantation of the cells from one growth site to another.
Claim 46
Dependent Claim
15 words
The method of claim 1 wherein the treatment is effected subsequent to tumor cell growth.
Claim 47
Dependent Claim
44 words
The composition according to claim 12 wherein the phosphatide is represented by formula ##STR4## wherein R 1 and R 2 are aliphatic hydrocarbons and R 3 is a ##STR5## --O--CH 2 --CH 2 .sup.⊕ NH 3 (ethanolamine), or --O--CH 2 --CHOH--CH 2 OH (glycerol).
Claim 48
Dependent Claim
15 words
The composition of claim 43 wherein cholesterol is present in a ratio with the phosphatide.
Claim 49
Dependent Claim
20 words
The composition of claim 43 wherein the lipids present in the lipid mixture are a phosphatide and free fatty acid.
Claim 50
Dependent Claim
15 words
The composition of claim 43 wherein R 2 is a fatty acid having unsaturated bonds.
Claim 51
Dependent Claim
22 words
The composition of claim 46 wherein R 2 is --(CH 2 ) 7 CH═CHCH 2 CH═CH(CH 2 ) 4 CH 3 .
Claim 52
Dependent Claim
24 words
The composition of claim 46 wherein R 2 is CH 2 CH 2 (CH 2 CH═CH) 4 (CH 2 ) 4 CH 3 .
References Cited (Backward Citations)
No citation records indexed.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1994-03-11 | 1994-09-10 | 1995-03-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-03-11 | 1998-09-10 | 1999-03-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-03-11 | 2002-09-10 | 2003-03-12 | $7700.00 | Window Closed / Lapsed |