CA1094455A - Tumor antidote - Google Patents
Tumor antidoteInfo
- Publication number
- CA1094455A CA1094455A CA277,458A CA277458A CA1094455A CA 1094455 A CA1094455 A CA 1094455A CA 277458 A CA277458 A CA 277458A CA 1094455 A CA1094455 A CA 1094455A
- Authority
- CA
- Canada
- Prior art keywords
- tumor
- formula
- antidote
- carbon atoms
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 29
- 239000000729 antidote Substances 0.000 title claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical compound NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 claims 2
- NJNWCIAPVGRBHO-UHFFFAOYSA-N 2-hydroxyethyl-dimethyl-[(oxo-$l^{5}-phosphanylidyne)methyl]azanium Chemical class OCC[N+](C)(C)C#P=O NJNWCIAPVGRBHO-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical class CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 abstract description 4
- 229940075522 antidotes Drugs 0.000 abstract description 2
- 241001465754 Metazoa Species 0.000 description 12
- MHFRGQHAERHWKZ-HHHXNRCGSA-N (R)-edelfosine Chemical compound CCCCCCCCCCCCCCCCCCOC[C@@H](OC)COP([O-])(=O)OCC[N+](C)(C)C MHFRGQHAERHWKZ-HHHXNRCGSA-N 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- -1 lysolecithin com-pounds Chemical class 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 1
- 238000011735 C3H mouse Methods 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000003468 Ehrlich Tumor Carcinoma Diseases 0.000 description 1
- PPQNQXQZIWHJRB-UHFFFAOYSA-N Methylcholanthrene Chemical compound C1=CC=C2C3=CC4=CC=C(C)C(CC5)=C4C5=C3C=CC2=C1 PPQNQXQZIWHJRB-UHFFFAOYSA-N 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 210000003024 peritoneal macrophage Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
TUMOR ANTIDOTE
Abstract of the disclosure:
The present invention provides tumor antidotes consisting of or containing a short chain synthetic lysolecithin analog.
Abstract of the disclosure:
The present invention provides tumor antidotes consisting of or containing a short chain synthetic lysolecithin analog.
Description
~IO~ -l6/S ~)0~
10~14~;
The present invention relates to a tumor antidote contain~
ing compour.ds of the lysolecithin type in a pharmaceutically usual formulation.
German Offenlegungsschrift No. 2,00~,3~2 and U.S. Patent No. 3,752,886 describe the use of synthetic lysolecithin com-pounds for increasing the resistance and for use as immullologic auxiliaries.
It is also known that lysolecithin analogs which may alternatively be called lysophosphatides increase phagocytosis of peritoneal macrophages. Moreover, after an injection of lysophosphatides, activated cells are formed which are able to increase the resistance of the body against damaging in-fluences.
It has now been found surprisingly that lysolecithin ana-logs of the formula I have a special effect on the growth of tumors.
The present invention provides therefore tumor antidotes consisting of or containing a compound of the formula I, in a pharmaceutically usual formulation.
Formula I-R2 ~ C - R3 wherein R1 is alkylcarbonyl (ester~ or alkoxyl (ether) having a chain length of 8 to 20 carbon atoms, preferably 16 to 18 carbon atoms;
R2 is H or CH3;
R3 is H, OH, alkylcarbonyl or alkoxyl having a chain length of
10~14~;
The present invention relates to a tumor antidote contain~
ing compour.ds of the lysolecithin type in a pharmaceutically usual formulation.
German Offenlegungsschrift No. 2,00~,3~2 and U.S. Patent No. 3,752,886 describe the use of synthetic lysolecithin com-pounds for increasing the resistance and for use as immullologic auxiliaries.
It is also known that lysolecithin analogs which may alternatively be called lysophosphatides increase phagocytosis of peritoneal macrophages. Moreover, after an injection of lysophosphatides, activated cells are formed which are able to increase the resistance of the body against damaging in-fluences.
It has now been found surprisingly that lysolecithin ana-logs of the formula I have a special effect on the growth of tumors.
The present invention provides therefore tumor antidotes consisting of or containing a compound of the formula I, in a pharmaceutically usual formulation.
Formula I-R2 ~ C - R3 wherein R1 is alkylcarbonyl (ester~ or alkoxyl (ether) having a chain length of 8 to 20 carbon atoms, preferably 16 to 18 carbon atoms;
R2 is H or CH3;
R3 is H, OH, alkylcarbonyl or alkoxyl having a chain length of
- 2 - ~
~r 109~4~5 OE 76/S 005 1 to 8, preferahly 1 to 3, carbon atoms, or benzyl;
R1 and R3 may be interchanged in princip]e:
R1 long-chain substituted = ~ -lysolecithin analog R2 long-chain substituted = B-lysolecithin analog R4 is O (phosphorylcholine deri-~P ~ ~ C~2 ~ CH2 -N (R5)3 vatives; R5 being H or ( ) lower alkyl having 1 to 3 carbon atoms, preferably CH3);
or O
- P - O - CH2 - CH2 N 2 (phosphoryl-ethanol-O (-~ - amine) The compound cited as example and hereinafter called ET-18-OCH3 in a thorou~hly abhreviated manner has the following formula Formula II:
H2C - o - (CH2)17 3 2 , 2 2 N (CH3)3 O (--) The compounds of the formula I may be prepared according to one of the methods described in the literature, for example according to Arnold, D., Weltzien, H.U. and 0. Westphal;
~ber die Synthese von Lysolecithinen und ihren ~theranaloga;
Liebigs Ann. Chem. 709, 234-239 (1967) 10944~5 HOE 76/S 005 -.
Weltzien, H.U. and O. Westphal;
O-Methylierte und O-acetylierte Lysolecithine;
Liebigs Ann. Chem. 709, 240-243 (1967) Eibl, H. and O. Westphal;
;. 5 Palmitoyl-propandiol-(1,3)-phosphorylcholin (2-Desoxy-lysoleci-thin~ und ~,~-Alkandiol-Analoga Liebigs Ann. Chem. 709, 244-247 (1967) The activity of compounds of the formula I against the A
growth of tumors is advantageously demonstrated on tumors of test animals. for this purpose, various experimental tumors are used, for example Ehrlich ascites tumor, a methylcholanthr ne-induced tumor and a myeloma tumor in mice, furthermore a chemically induced rat tumor.
The anti-tumor substances are administered parenterally to the tumor-carrying test animals, preferably by intravenous, intra- or subcutaneous injection. Oral administration is possible when the tumor antidote is used in a physiologically tolerable formulation, for example capsules.
t An advantageous dosage rate for parenteral administration is from about 0.05 to 5 mg/kg of body welght.
Especially efficient are the compounds of the formula II
and those which contain OH or H instead of the methoxyl group of formula II. At low concentration, they cause a reduction of the growth rate of tumors and at mean concentration, a re-gression of the tumors is often observed. After regression of ; the t~mors, the test animals display a specific resistance against attempts to implant again a tumor of the same kind:
the t~mor does not grow any more. In order to let persist the .
: ' ' ,' , ~09~4SS
tumor an-tidotes in the circulatory system for a prolonged period, it is often useful to administer the medicaments daily or in in-tervals of 2 or 3 days.
The following test examples illustrate the activity of the tumor medicaments of the invention.
TEST EXAMPI,E 1:
Mice carrying Ehrlich ascites carcinoma cells (see Table 1) were treated the 7th day after the tumor inoculation with the anti-tumor compound ET-18-OCH3 by means of intravenous injection.
The survival rate was evaluated of the mice which had been inoculated intraperitoneally with a varying number of tumor cells.
Table 1 shows the test resul~s and the dependence of the efficien cy of the tumor antidote ET-18-OCH3 on the daily dose intravenous-ly administered, expressed as ratio of surviving animals to total number of mice.
T A_B L E 1:
Daily doses of Number of tumor cells applied per mouse fox ET-18-OCH3 tumor inoculation per 20 g mouse .. . ..
1 x 10 1 x 104 5 x 104 1 x 105 5 x 105 1 ~g 0/5 3/5 3/5 3/5 1/5 10 ~g 0/5 1/5 1/5 1/5 1/5 100 ~g 0/5 3/5 2/5 3/5 1/5 ` Control (without ET-18-OCH3) 0/5 0/5 0/5 0/5 0/5 )Surviving/total number of test animals : ' ! , . , ~
: ' ` " ' .` ` ~ ~., "' . " : ' .: ' ' ~ '`'`
, ' ' HO~ 76/S 005 TEST EXAMPI.E 2:
By intravenous injection of ET-18-OH (see formula II, OCH3 being replaced by OH~, the growth of methylcholanthrene-induced tumor cells in (Ba1b/c x C57hl/6)F1 mlce can be controlled.
The following Table 2 s~.ows the possibility to vary the start of treatment within several daysafter inoculation of the tumor.
At a corresponding dosage rate of the tumor antidote, in each case the ratio of surviving test animals to their total number is more favorable than that obtained with untreated control animals, of which no mouse survives.
Table 2 shows the survival rate of the animals at graduated start of treatment. The tumor antidote was intravenously admini-stered each day for a fortnight.
T A B L E 2:
Start of treat- dose ET-18-OH/20 g mouse mentlday 1 ~g 10 ~g 100 ~g + ~ 2/5 3/5 4/5 + 3 3/5 3/5 2/5 + 5 3/5 4/5 3/5 + 7 2/5 1/5 3/5 + 9 3/5 2/5 4/5 Control 0/5 ) Surviving/total number of test animals A comparable test result was obtained when the tumor anti-dote was administered by intracutaneous instead of intravenous injection. Comparable survival rates of the animals are obtain-ed when from 10 to 50 llg per mouse and day of the compound HOE 7~/S ~05 ET-18-OH, dissolved in isotonic saline so]ution in a concen--tration of from 10 to 100 ~g per m] are orally administered.
TEST EXAMPLE 3:
5 x 104 myeloma tumor cells (Potter x 5563) were subcutane-ously inoculated in C3H mice. The mice were then treated with the tumor antidote ET-18-OCH3 by administering 10~g/20 g mouse intracutaneously for 14 days at a place remote from the tumor.
The following Table 3 shows the survival rate of the test animals, depending on the start of treatment with the tumor antidote.
T A B L E 3:
Start of treat- Surviving/total number mentlday of test animals + 1 4/5 + 7 3/5 + 11 3/5 + 15 1/5 Control (without ET-18-OCH3) 0/5 ~`
: ~ . ~ . .: . ,
~r 109~4~5 OE 76/S 005 1 to 8, preferahly 1 to 3, carbon atoms, or benzyl;
R1 and R3 may be interchanged in princip]e:
R1 long-chain substituted = ~ -lysolecithin analog R2 long-chain substituted = B-lysolecithin analog R4 is O (phosphorylcholine deri-~P ~ ~ C~2 ~ CH2 -N (R5)3 vatives; R5 being H or ( ) lower alkyl having 1 to 3 carbon atoms, preferably CH3);
or O
- P - O - CH2 - CH2 N 2 (phosphoryl-ethanol-O (-~ - amine) The compound cited as example and hereinafter called ET-18-OCH3 in a thorou~hly abhreviated manner has the following formula Formula II:
H2C - o - (CH2)17 3 2 , 2 2 N (CH3)3 O (--) The compounds of the formula I may be prepared according to one of the methods described in the literature, for example according to Arnold, D., Weltzien, H.U. and 0. Westphal;
~ber die Synthese von Lysolecithinen und ihren ~theranaloga;
Liebigs Ann. Chem. 709, 234-239 (1967) 10944~5 HOE 76/S 005 -.
Weltzien, H.U. and O. Westphal;
O-Methylierte und O-acetylierte Lysolecithine;
Liebigs Ann. Chem. 709, 240-243 (1967) Eibl, H. and O. Westphal;
;. 5 Palmitoyl-propandiol-(1,3)-phosphorylcholin (2-Desoxy-lysoleci-thin~ und ~,~-Alkandiol-Analoga Liebigs Ann. Chem. 709, 244-247 (1967) The activity of compounds of the formula I against the A
growth of tumors is advantageously demonstrated on tumors of test animals. for this purpose, various experimental tumors are used, for example Ehrlich ascites tumor, a methylcholanthr ne-induced tumor and a myeloma tumor in mice, furthermore a chemically induced rat tumor.
The anti-tumor substances are administered parenterally to the tumor-carrying test animals, preferably by intravenous, intra- or subcutaneous injection. Oral administration is possible when the tumor antidote is used in a physiologically tolerable formulation, for example capsules.
t An advantageous dosage rate for parenteral administration is from about 0.05 to 5 mg/kg of body welght.
Especially efficient are the compounds of the formula II
and those which contain OH or H instead of the methoxyl group of formula II. At low concentration, they cause a reduction of the growth rate of tumors and at mean concentration, a re-gression of the tumors is often observed. After regression of ; the t~mors, the test animals display a specific resistance against attempts to implant again a tumor of the same kind:
the t~mor does not grow any more. In order to let persist the .
: ' ' ,' , ~09~4SS
tumor an-tidotes in the circulatory system for a prolonged period, it is often useful to administer the medicaments daily or in in-tervals of 2 or 3 days.
The following test examples illustrate the activity of the tumor medicaments of the invention.
TEST EXAMPI,E 1:
Mice carrying Ehrlich ascites carcinoma cells (see Table 1) were treated the 7th day after the tumor inoculation with the anti-tumor compound ET-18-OCH3 by means of intravenous injection.
The survival rate was evaluated of the mice which had been inoculated intraperitoneally with a varying number of tumor cells.
Table 1 shows the test resul~s and the dependence of the efficien cy of the tumor antidote ET-18-OCH3 on the daily dose intravenous-ly administered, expressed as ratio of surviving animals to total number of mice.
T A_B L E 1:
Daily doses of Number of tumor cells applied per mouse fox ET-18-OCH3 tumor inoculation per 20 g mouse .. . ..
1 x 10 1 x 104 5 x 104 1 x 105 5 x 105 1 ~g 0/5 3/5 3/5 3/5 1/5 10 ~g 0/5 1/5 1/5 1/5 1/5 100 ~g 0/5 3/5 2/5 3/5 1/5 ` Control (without ET-18-OCH3) 0/5 0/5 0/5 0/5 0/5 )Surviving/total number of test animals : ' ! , . , ~
: ' ` " ' .` ` ~ ~., "' . " : ' .: ' ' ~ '`'`
, ' ' HO~ 76/S 005 TEST EXAMPI.E 2:
By intravenous injection of ET-18-OH (see formula II, OCH3 being replaced by OH~, the growth of methylcholanthrene-induced tumor cells in (Ba1b/c x C57hl/6)F1 mlce can be controlled.
The following Table 2 s~.ows the possibility to vary the start of treatment within several daysafter inoculation of the tumor.
At a corresponding dosage rate of the tumor antidote, in each case the ratio of surviving test animals to their total number is more favorable than that obtained with untreated control animals, of which no mouse survives.
Table 2 shows the survival rate of the animals at graduated start of treatment. The tumor antidote was intravenously admini-stered each day for a fortnight.
T A B L E 2:
Start of treat- dose ET-18-OH/20 g mouse mentlday 1 ~g 10 ~g 100 ~g + ~ 2/5 3/5 4/5 + 3 3/5 3/5 2/5 + 5 3/5 4/5 3/5 + 7 2/5 1/5 3/5 + 9 3/5 2/5 4/5 Control 0/5 ) Surviving/total number of test animals A comparable test result was obtained when the tumor anti-dote was administered by intracutaneous instead of intravenous injection. Comparable survival rates of the animals are obtain-ed when from 10 to 50 llg per mouse and day of the compound HOE 7~/S ~05 ET-18-OH, dissolved in isotonic saline so]ution in a concen--tration of from 10 to 100 ~g per m] are orally administered.
TEST EXAMPLE 3:
5 x 104 myeloma tumor cells (Potter x 5563) were subcutane-ously inoculated in C3H mice. The mice were then treated with the tumor antidote ET-18-OCH3 by administering 10~g/20 g mouse intracutaneously for 14 days at a place remote from the tumor.
The following Table 3 shows the survival rate of the test animals, depending on the start of treatment with the tumor antidote.
T A B L E 3:
Start of treat- Surviving/total number mentlday of test animals + 1 4/5 + 7 3/5 + 11 3/5 + 15 1/5 Control (without ET-18-OCH3) 0/5 ~`
: ~ . ~ . .: . ,
Claims (2)
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A tumor antidote comprising a compound of the formula I
wherein R1 is alkylcarbonyl (ester) or alkoxyl (ether) having a chain length of 8 to 20 carbon atoms;
R2 is H or CH3;
R3 is H, OH, alkylcarbonyl or alkoxyl having a chain length of 1 to 8 carbon atoms, or benzyl;
R1 and R3 may be interchanged;
R4 is (phosphorylcholine derivatives;
R6 being H or lower alkyl hav-ing 1 to 3 carbon atoms);
or (phosphoryl-ethanolamine), in a pharmaceutical formulation, said antidote containing from 0.01 to 10 mg/ml of the compound of the formula I in a physiologically tolerable formulation suitable for oral administration.
wherein R1 is alkylcarbonyl (ester) or alkoxyl (ether) having a chain length of 8 to 20 carbon atoms;
R2 is H or CH3;
R3 is H, OH, alkylcarbonyl or alkoxyl having a chain length of 1 to 8 carbon atoms, or benzyl;
R1 and R3 may be interchanged;
R4 is (phosphorylcholine derivatives;
R6 being H or lower alkyl hav-ing 1 to 3 carbon atoms);
or (phosphoryl-ethanolamine), in a pharmaceutical formulation, said antidote containing from 0.01 to 10 mg/ml of the compound of the formula I in a physiologically tolerable formulation suitable for oral administration.
2. A tumor antidote as claimed in claim 1 in which the compound of the formula I has the formula
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2619686A DE2619686C2 (en) | 1976-05-04 | 1976-05-04 | Use of a lysolecithin for tumor treatment |
| DEP2619686.1 | 1976-05-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1094455A true CA1094455A (en) | 1981-01-27 |
Family
ID=5977045
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA277,458A Expired CA1094455A (en) | 1976-05-04 | 1977-05-03 | Tumor antidote |
Country Status (15)
| Country | Link |
|---|---|
| JP (1) | JPS52134027A (en) |
| AU (1) | AU517586B2 (en) |
| BE (1) | BE854270A (en) |
| CA (1) | CA1094455A (en) |
| DE (1) | DE2619686C2 (en) |
| FR (1) | FR2364656A1 (en) |
| GB (1) | GB1583661A (en) |
| IE (1) | IE44927B1 (en) |
| IL (1) | IL51988A (en) |
| IT (1) | IT1071329B (en) |
| LU (1) | LU77248A1 (en) |
| NL (1) | NL189672C (en) |
| NZ (1) | NZ183981A (en) |
| SE (1) | SE7705071L (en) |
| ZA (1) | ZA772649B (en) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5396311A (en) * | 1977-01-29 | 1978-08-23 | Toyama Chem Co Ltd | Anti-cander drugs containing lysolecithins |
| JPS5528955A (en) * | 1978-08-24 | 1980-02-29 | Toyama Chem Co Ltd | Novel glycerophosphoric acid derivative, its salt, their preparation, and carcinostatic agent containing the same. |
| GB2046092B (en) * | 1979-03-05 | 1983-11-02 | Toyama Chemical Co Ltd | Pharmaceutical composition containing a lysophospholid and a phospholipid |
| US4408052A (en) * | 1980-02-27 | 1983-10-04 | Takeda Chemical Industries, Ltd. | Phospholipid carbamates |
| US4551532A (en) * | 1980-05-08 | 1985-11-05 | Takeda Chemical Industries, Ltd. | Ethylene glycol derivatives having anti-protozoan, anti-fungal and anti-tumor activity |
| EP0050327B1 (en) * | 1980-10-21 | 1984-06-20 | Roche Diagnostics GmbH | Phospholipids that contain sulphur, process for their preparation and medicines containing these compounds |
| JPS5772914A (en) * | 1980-10-22 | 1982-05-07 | Takeda Chem Ind Ltd | Antitumor agent |
| EP0061872B1 (en) * | 1981-03-30 | 1985-08-07 | Takeda Chemical Industries, Ltd. | Ethyleneglycol derivatives, their production and use |
| DE3127503A1 (en) * | 1981-07-11 | 1983-02-17 | Boehringer Mannheim Gmbh, 6800 Mannheim | NEW PHOSPHOLIPIDS, METHOD FOR THE PRODUCTION THEREOF, AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS |
| DE3131524A1 (en) * | 1981-08-08 | 1983-02-24 | Röhm GmbH, 6100 Darmstadt | METHOD FOR PRODUCING PHYSIOLOGICAL EFFECTORS |
| US4562179A (en) * | 1982-04-19 | 1985-12-31 | Fujisawa Pharmaceutical Co., Ltd. | Phospholipid derivatives, and pharmaceutical composition of the same |
| DE3239817A1 (en) * | 1982-07-06 | 1984-01-12 | Max Planck Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen | NEW GLYCER DERIVATIVES FOR THE SYNTHESIS OF PHOSPHOLIPIDES |
| DE3239858A1 (en) * | 1982-07-06 | 1984-01-12 | Max Planck Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen | NEW D-MANNITE DERIVATIVES AS STARTING PRODUCTS FOR THE SYNTHESIS OF PHOSPHOLIPIDES |
| EP0103877B1 (en) * | 1982-09-21 | 1987-01-07 | Fujisawa Pharmaceutical Co., Ltd. | Phosphate derivatives, process for preparation thereof and pharmaceutical compositions of the same |
| US4710579A (en) * | 1984-11-09 | 1987-12-01 | Takeda Chemical Industries, Ltd. | 2-(acetoacetyloxy)-3-(octadecyloxy)propyl-3-trimethylammoniopropyl phosphate or a pharmaceutically acceptable salt thereof |
| US4761404A (en) * | 1985-07-01 | 1988-08-02 | Merck & Co., Inc. | Phospholipid analogs useful as PAF synthesis inhibitors |
| DE3662197D1 (en) | 1985-07-15 | 1989-04-06 | Takeda Chemical Industries Ltd | 2-alkanoyloxypropane derivatives, their production and use |
| JPS6294A (en) * | 1986-05-09 | 1987-01-06 | Toyama Chem Co Ltd | Novel glycerophosphoric acid derivative and salt and production thereof |
| JP2561478B2 (en) * | 1986-07-22 | 1996-12-11 | 武田薬品工業株式会社 | Glycerin derivative |
| US5036152A (en) * | 1988-03-10 | 1991-07-30 | Hoechst-Roussel Pharmaceuticals Incorporated | Alkoxycarbonylalkylphospholipids and alkylaminocarbonylalkylphospholipids |
| US4888328A (en) * | 1988-03-10 | 1989-12-19 | Hoeschst-Roussel Incorporated | Alkoxycarbonylalkylphospholipids and alkylaminocarbonylalkylphospholipids |
| DE3906952A1 (en) * | 1989-03-04 | 1990-09-06 | Boehringer Mannheim Gmbh | (3- (C (DOWN ARROW)) (DOWN ARROW) (DOWN ARROW) 6 (DOWN ARROW) -C (DOWN ARROW) 1 (DOWN ARROW) (DOWN ARROW) 8 (DOWN ARROW)) ALKANSULFINYL AND 2 SULPHONE -METHOXYMETHYL-PROPYL) - (2-TRIMETHYLAMMONIO-ETHYL) PHOSPHATES, METHOD FOR PRODUCING THE MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS |
| DE3918082A1 (en) * | 1989-06-02 | 1991-01-24 | Max Planck Gesellschaft | AGENT FOR AUTOIMMUNE DISEASES |
| DE3935580C2 (en) * | 1989-10-25 | 1998-05-28 | Medmark Pharma Gmbh | Use of an active pharmaceutical ingredient for the treatment of HIV infections |
| EP0581793A1 (en) * | 1991-04-25 | 1994-02-09 | University Of British Columbia | Phosphonates and phosphinates as anti-cancer, -inflammatory, -allergy and -myocarditis agents |
| ES2034885B1 (en) * | 1991-07-10 | 1994-03-01 | Menarini Lab | PROCEDURE FOR THE PREPARATION OF CETOALQUILGLICEROFOSFOLIPIDOS. |
| KR100381449B1 (en) * | 1994-10-14 | 2003-07-18 | 더 리포좀 컴퍼니, 인코퍼레이티드 | Application of ether lipid liposomal enzymes to pharmaceuticals |
| USRE39042E1 (en) * | 1996-02-16 | 2006-03-28 | The Liposome Company, Inc. | Etherlipid-containing multiple lipid liposomes |
| US5942246A (en) * | 1996-02-16 | 1999-08-24 | The Liposome Company, Inc. | Etherlipid containing multiple lipid liposomes |
| US6007839A (en) * | 1996-02-16 | 1999-12-28 | The Liposome Company, Inc. | Preparation of pharmaceutical compositions containing etherlipid-containing multiple lipid liposomes |
| US6667053B1 (en) | 1996-02-16 | 2003-12-23 | Elan Pharmaceuticals, Inc. | D and L etherlipid stereoisomers and liposomes |
| US5965159A (en) | 1996-02-16 | 1999-10-12 | The Liposome Company, Inc. | Etherlipid-containing multiple lipid liposomes |
| US6135426A (en) * | 1998-01-07 | 2000-10-24 | Briggs And Stratton Corporation | Priming system for internal combustion engines |
| EP2091520B1 (en) | 2006-11-10 | 2012-02-22 | Alphaptose Gmbh | Oral dosage form comprising tri-substituted glycerol compounds |
| CN101606061B (en) * | 2006-11-10 | 2014-01-22 | 阿尔法普托斯有限公司 | Methods and compositions for detecting receptor ligand mimetics |
| US8637688B2 (en) * | 2006-12-20 | 2014-01-28 | Julia Diederichs | Topical dosage form comprising tri-substituted glycerol compounds |
| US20100136029A1 (en) * | 2006-12-20 | 2010-06-03 | Universitatsklinikum Hamburg-Eppendorf | Use of Tri-Substituted Glycerol Compounds for the Treatment of Hematological Malignancies |
| WO2013156630A1 (en) | 2012-04-20 | 2013-10-24 | Alphaptose Gmbh | S-enantiomer of a tri-substituted glycerol compound |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2009342C3 (en) * | 1970-02-27 | 1980-12-18 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V., 3400 Goettingen | Use of glycerol alkyl ether (l) phosphoric acid (3) monocholine esters |
| DE2009343C3 (en) * | 1970-02-27 | 1980-10-23 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V., 3400 Goettingen | Use of lysolecithins as immunological adjuvants |
| DE2009341C3 (en) * | 1970-02-27 | 1979-06-21 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V., 3400 Goettingen | 3-Octadecyloxy-propanol- (l) -phosphoric acid monocholine ester and process for its preparation |
| DE2033361C3 (en) * | 1970-07-06 | 1980-02-21 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V., 3400 Goettingen | Acylpropanediol- (13) -phosphoric acid choline ester and process for their preparation |
-
1976
- 1976-05-04 DE DE2619686A patent/DE2619686C2/en not_active Expired
-
1977
- 1977-04-29 NL NLAANVRAGE7704723,A patent/NL189672C/en not_active IP Right Cessation
- 1977-05-02 NZ NZ183981A patent/NZ183981A/en unknown
- 1977-05-02 SE SE7705071A patent/SE7705071L/en unknown
- 1977-05-02 IL IL51988A patent/IL51988A/en unknown
- 1977-05-02 IT IT23094/77A patent/IT1071329B/en active
- 1977-05-03 IE IE888/77A patent/IE44927B1/en not_active IP Right Cessation
- 1977-05-03 ZA ZA00772649A patent/ZA772649B/en unknown
- 1977-05-03 CA CA277,458A patent/CA1094455A/en not_active Expired
- 1977-05-03 GB GB18431/77A patent/GB1583661A/en not_active Expired
- 1977-05-03 AU AU24819/77A patent/AU517586B2/en not_active Expired
- 1977-05-03 LU LU77248A patent/LU77248A1/xx unknown
- 1977-05-04 FR FR7713522A patent/FR2364656A1/en active Granted
- 1977-05-04 BE BE177280A patent/BE854270A/en not_active IP Right Cessation
- 1977-05-04 JP JP5194477A patent/JPS52134027A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| LU77248A1 (en) | 1977-12-13 |
| IL51988A (en) | 1981-05-20 |
| SE7705071L (en) | 1977-11-05 |
| ZA772649B (en) | 1978-04-26 |
| JPS52134027A (en) | 1977-11-09 |
| DE2619686A1 (en) | 1977-11-24 |
| NZ183981A (en) | 1980-04-28 |
| IL51988A0 (en) | 1977-07-31 |
| DE2619686C2 (en) | 1986-08-07 |
| IE44927L (en) | 1977-11-04 |
| IE44927B1 (en) | 1982-05-19 |
| JPS6146455B2 (en) | 1986-10-14 |
| IT1071329B (en) | 1985-04-02 |
| NL7704723A (en) | 1977-11-08 |
| FR2364656A1 (en) | 1978-04-14 |
| NL189672B (en) | 1993-01-18 |
| NL189672C (en) | 1993-06-16 |
| AU517586B2 (en) | 1981-08-13 |
| FR2364656B1 (en) | 1980-03-07 |
| AU2481977A (en) | 1978-11-09 |
| GB1583661A (en) | 1981-01-28 |
| BE854270A (en) | 1977-11-04 |
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