GB1583661A - Tumour antidote - Google Patents
Tumour antidote Download PDFInfo
- Publication number
- GB1583661A GB1583661A GB18431/77A GB1843177A GB1583661A GB 1583661 A GB1583661 A GB 1583661A GB 18431/77 A GB18431/77 A GB 18431/77A GB 1843177 A GB1843177 A GB 1843177A GB 1583661 A GB1583661 A GB 1583661A
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- United Kingdom
- Prior art keywords
- tumor
- group
- compound
- pharmaceutical preparation
- och3
- Prior art date
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- 206010028980 Neoplasm Diseases 0.000 title claims description 31
- 239000000729 antidote Substances 0.000 title claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 24
- 241001465754 Metazoa Species 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims 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 claims description 11
- 241000699670 Mus sp. Species 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 241000699666 Mus <mouse, genus> Species 0.000 claims description 6
- 210000004881 tumor cell Anatomy 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 4
- 238000011081 inoculation Methods 0.000 claims description 4
- 230000004083 survival effect Effects 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- 230000000259 anti-tumor effect Effects 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 230000037396 body weight Effects 0.000 claims description 3
- 210000004027 cell Anatomy 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 3
- 206010003445 Ascites Diseases 0.000 claims description 2
- 238000011735 C3H mouse Methods 0.000 claims description 2
- 201000009030 Carcinoma Diseases 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000007903 gelatin capsule Substances 0.000 claims description 2
- 238000010253 intravenous injection Methods 0.000 claims description 2
- 238000007911 parenteral administration Methods 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 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 description 3
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical compound NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 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
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- -1 for example Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000001900 immune 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
- 239000000203 mixture Substances 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000003024 peritoneal macrophage Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical class 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
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000243 solution Substances 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
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 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
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- 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)
Description
(54) TUMOR ANTIDOTE
(71) We, MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN E.V., a body corporate organised according to the laws of the Federal Republic of Germany, of 10 Bunsenstrasse, 3400 Göttingen, Federal
Republic of Germany, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- The present invention relates to a tumor antidote.
German Offenlegungsschrift No. 2 009 342 (U.K. Patent No. 1,334,137) and
U.S. Patent No. 3 752 886 describe the use of synthetic lysolecithin compounds for increasing resistance to diseases and tumors and for use as immunological auxiliaries.
It is also known that lysolecithin analogues, 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 influences.
It has now been found surprisingly that certain lysolecithin analogues have a special effect on the growth of tumors.
The present invention provides a pharmaceutical preparation which comprises, in admixture or conjunction with a pharmaceutically suitable carrier, a compound of the general formula I
wherein
R, represents an alkylcarbonyl or alkoxy group having from 8 to 20 carbon atoms, preferably 16 to 18 carbon atoms;
R2 represents a hydrogen atom or a methyl group;
R3 represents a hydrogen atom, a hydroxyl group, an alkyl-carbonyl or alkoxy group having a chain length of from 1 to 8, preferably 1 to 3, carbon atoms, or a benzyl group;
R, and R3 may be interchanged;
R4 represents the group
(phosphorylcholine derivatives) in which
R5 represents a hydrogen atom or a lower alkyl group having I to 3 carbon atoms, preferably a methyl group, or
R4 represents the group
(phosphoryl-ethanol- amine) with the exception of those compounds in which R2 represents a hydrogen atom and R3 represents a hydrogen atom or a hydroxyl group, and those in which R2 represents a methyl group and R3 represents a hydroxyl group.
Those compounds in which R, is a long chain group are analogous of alysolecithin, whereas those in which R3 is the long chain group are p-lysolecithin analogues.
The compound cited as example and hereinafter called ET-18-OCH3 in a thoroughly abbreviated manner has the following formula II
The compounds of the formula I may be prepared according to any of the methods described in the literature, for example according to
Arnold, D., Weltzien, H. U. and 0. Westphal; Uber die Synthese von
Lysolecithinen und ihren Atheranaloga; Liebigs Ann. Chem. 709, 234-239 (1967)
Weltzien, H. U. and 0. Westphal; O-methylierte und O-acetylierte
Lysolecithine; Liebigs Ann. Chem. 709, 240243 (1967)
Eibl. H. and 0. Westphal; Palmitoyl - propandiol - (1,3) - phosphorylcholin (2 - Desoxy - lysolecithin) und w,w - Alkandiol - Analoga Liebigs Ann. Chem.
709 244-247 (1967)
The activity of compounds of the formula I against the 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 methylcholanthrene-induced tumor and a myeloma tumor in mice, furthermore a chemically induced rat tumor.
The anti-tumor substances may be administered parenterally to the tumorcarrying test animals or to a patient preferably by intravenous, intra- or subcutaneous injection. Oral administration also is possible when the tumor antidote is used in a physiologically tolerable formulation, for example, soft and hard capsules and tablets.
The pharmaceutical preparations of the invention are, therefore, for example, in a form suitable for parenteral, especially intravenous, intracutaneous or subcutaneous administration, or for oral administration. There may be used any pharmaceutical carrier suitable for the chosen galenic form.
The preparations may be in unit dosage form. An advantageous dosage for parenteral administration is from 0.05 to 5 mg/kg of a compound of formula I body weight, and for oral administration from 0.01 to 10 mg/kg body weight. The preparations may contain from 0.05 to 5 mg and from 0.01 to 10 mg of the compound per ml, respectively. When the preparation is for oral administration, it advantageously comprises a solution or suspension of the compound of formula I in a soft gelatin capsule.
Especially efficient are the compounds of the formula II. At low concentration, they cause a reduction of the growth rate of tumors and at mean concentration, a regression of the tumors is often observed. After regression of the tumors, the test animals display a specific resistance to attempts to implant again a tumor of the same kind: the tumor does not grow any more. In order to enable the compound of formula I to remain in the circulatory system for a prolonged period, it is often useful to administer pharmaceutical preparation of the invention daily or in intervals of 2 or 3 days.
The invention further provides a method of treating an animal having a tumor, which comprises administering to the animal a compound of the general formula I.
The amount of the compound administered is preferably from 0.05 to 5 mg parenterally and from 0.01 to 10 mg orally. The animal is especially a human being.
The following Examples illustrate the activity of the tumor medicaments of the invention.
TEST EXAMPLE 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 I shows the test results and the dependence of the efficiency of the tumor antidote ET-18-OCH3 on the daily dose intravenously administered, expressed as ratio of surviving animals to total number of mice.
TABLE 1
Daily doses of Number of tumor cells applied per ET- 1 8-OCH3 mouse for tumor inoculation per 20 g mouse 1x103 1x104 5x104 lx 105 5x 5x105 I Mg 0/5*) 3/5 3/5 3/5 1/5 10 ssg 0/5 1/5 1/5 1/5 1/5 100 mug 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
TEST EXAMPLE 2: 5x104 myeloma tumor cells (Potterx5563) were subcutaneously 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.
TABLE 3
Start of treatment/day Surviving/total number of test animals
+1 4/5
+7 3/5
+11 3/5
+15 1/5
Control (without ET-18-OCH3) 0/5
WHAT WE CLAIM IS:
1. A pharmaceutical preparation which comprises, in admixture or conjunction with a pharmaceutically suitable carrier, a compound of the general formula I
wherein
R, represents an alkylcarbonyl or alkoxy group having a chain length of 8 to 20 carbon atoms;
R2 represents a hydrogen atom or a methyl group;
R3 represents a hydrogen atom, a hydroxyl group, or an alkylcarbonyl or alkoxy group having a chain length of 1 to 8 carbon atoms, or represents a benzyl group;
R, and R3 being interchangeable;
R4 represents the group
in which
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (1)
- **WARNING** start of CLMS field may overlap end of DESC **.The following Examples illustrate the activity of the tumor medicaments of the invention.TEST EXAMPLE 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 I shows the test results and the dependence of the efficiency of the tumor antidote ET-18-OCH3 on the daily dose intravenously administered, expressed as ratio of surviving animals to total number of mice.TABLE 1 Daily doses of Number of tumor cells applied per ET- 1 8-OCH3 mouse for tumor inoculation per 20 g mouse 1x103 1x104 5x104 lx 105 5x 5x105 I Mg 0/5*) 3/5 3/5 3/5 1/5 10 ssg 0/5 1/5 1/5 1/5 1/5 100 mug 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 TEST EXAMPLE 2: 5x104 myeloma tumor cells (Potterx5563) were subcutaneously 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.TABLE 3 Start of treatment/day Surviving/total number of test animals +1 4/5 +7 3/5 +11 3/5 +15 1/5 Control (without ET-18-OCH3) 0/5 WHAT WE CLAIM IS:1. A pharmaceutical preparation which comprises, in admixture or conjunction with a pharmaceutically suitable carrier, a compound of the general formula Iwherein R, represents an alkylcarbonyl or alkoxy group having a chain length of 8 to 20 carbon atoms; R2 represents a hydrogen atom or a methyl group; R3 represents a hydrogen atom, a hydroxyl group, or an alkylcarbonyl or alkoxy group having a chain length of 1 to 8 carbon atoms, or represents a benzyl group; R, and R3 being interchangeable; R4 represents the groupin whichR5 represents a hydrogen atom or a lower alkyl group having 1 to 3 carbon atoms, or R4 represents the groupwith the exception of those compounds in which R2 represents a hydrogen atom and R3 represents a hydrogen atom or a hydroxyl group, and those in which R2 represents a methyl group and R3 represents a hydroxyl group.2. A pharmaceutical preparation as claimed in Claim 1, wherein R, representse an alkylcarbonyl or alkoxy group having a chain length of from 16 to 18 carbon atoms and R3 represents an alkylcarbonyl or alkoxy group having a chain length of from 1 to 3 carbon atoms, R1 and R3 being interchangeable, and R5 represents a methyl group.3. A pharmaceutical preparation as claimed in Claim 1, wherein R, represents an alkoxy group having a chain length of 18 carbon atoms, R2 represents a hydrogen atom, R3 represents a methoxy group, and R4 represents the group4. A pharmaceutical preparation as claimed in any one of Claims 1 to 3, in a form suitable for parenteral administration.5. A pharmaceutical preparation as claimed in Claim 4, in a form suitable for intraveneous, intracutaneous or subcutaneous administration.6. A pharmaceutical preparation as claimed in Claim 4 or Claim 5, which comprises from 0.05 to 5 mg of the compound of formula I per ml.7. A pharmaceutical preparation as claimed in any one of Claims 1 to 4, in a form suitable for oral administration.8. A pharmaceutical preparation as claimed in claim 7, which comprises from 0.01 to 10 mg of the compound of formula I per ml.9. A pharmaceutical preparation as claimed in Claim 7 or Claim 8, in the form of a soft gelatin capsule.10. A method of treating a non-human animal having a tumor, which comprises administering to the animal a compound as defined in any one of Claims 1 to 3.11. A method as claimed in Claim 10, wherein the compound is administered intravenously, intracutaneously or subcutaneously.13. A method as claimed in Claim 10, wherein the compound is administered orally.14. A method as claimed in Claim 13, wherein from 0.01 to 10 mg of the compound is administered per kg body weight.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2619686A DE2619686C2 (en) | 1976-05-04 | 1976-05-04 | Use of a lysolecithin for tumor treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1583661A true GB1583661A (en) | 1981-01-28 |
Family
ID=5977045
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB18431/77A Expired GB1583661A (en) | 1976-05-04 | 1977-05-03 | Tumour 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) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4562179A (en) * | 1982-04-19 | 1985-12-31 | Fujisawa Pharmaceutical Co., Ltd. | Phospholipid derivatives, and pharmaceutical composition of the same |
| US4675430A (en) * | 1985-07-15 | 1987-06-23 | Takeda Chemical Industries, Inc. | 2-alkanoyloxy-3-(N-octadecylcarbamoyloxy)propyl 2-trimethylaminoethyl phosphate |
| 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 |
| US4889953A (en) * | 1986-07-22 | 1989-12-26 | Takeda Chemical Industries, Ltd. | Glycerol derivatives, their production and use |
| WO1993001196A1 (en) * | 1991-07-10 | 1993-01-21 | Laboratorios Menarini S.A. | Ketoalkylglycerophospholipids having antitumor and anti-platelet aggregation activities, processes for the preparation thereof and pharmaceutical compositions therefrom |
| US5762958A (en) * | 1994-10-14 | 1998-06-09 | The Liposome Company, Inc. | Multilipid component ether lipid liposomes |
| US5942246A (en) * | 1996-02-16 | 1999-08-24 | The Liposome Company, Inc. | Etherlipid containing multiple lipid liposomes |
| US5965159A (en) * | 1996-02-16 | 1999-10-12 | 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 |
| USRE39042E1 (en) * | 1996-02-16 | 2006-03-28 | The Liposome Company, Inc. | Etherlipid-containing multiple lipid liposomes |
| WO2008074572A1 (en) * | 2006-12-20 | 2008-06-26 | Universitätsklinikum Hamburg-Eppendorf | Use of tri-substituted glycerol compounds for the treatment of hematological malignancies |
Families Citing this family (26)
| 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 |
| 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 |
| US4761404A (en) * | 1985-07-01 | 1988-08-02 | Merck & Co., Inc. | Phospholipid analogs useful as PAF synthesis inhibitors |
| JPS6294A (en) * | 1986-05-09 | 1987-01-06 | Toyama Chem Co Ltd | Novel glycerophosphoric acid derivative and salt and production thereof |
| 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 |
| 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 |
| 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
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4562179A (en) * | 1982-04-19 | 1985-12-31 | Fujisawa Pharmaceutical Co., Ltd. | Phospholipid derivatives, and pharmaceutical composition 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 |
| US4675430A (en) * | 1985-07-15 | 1987-06-23 | Takeda Chemical Industries, Inc. | 2-alkanoyloxy-3-(N-octadecylcarbamoyloxy)propyl 2-trimethylaminoethyl phosphate |
| US4889953A (en) * | 1986-07-22 | 1989-12-26 | Takeda Chemical Industries, Ltd. | Glycerol derivatives, their production and use |
| WO1993001196A1 (en) * | 1991-07-10 | 1993-01-21 | Laboratorios Menarini S.A. | Ketoalkylglycerophospholipids having antitumor and anti-platelet aggregation activities, processes for the preparation thereof and pharmaceutical compositions therefrom |
| US5762958A (en) * | 1994-10-14 | 1998-06-09 | The Liposome Company, Inc. | Multilipid component ether lipid liposomes |
| US5942246A (en) * | 1996-02-16 | 1999-08-24 | The Liposome Company, Inc. | Etherlipid containing multiple lipid liposomes |
| US5965159A (en) * | 1996-02-16 | 1999-10-12 | 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 |
| US6180137B1 (en) | 1996-02-16 | 2001-01-30 | The Liposome Company, Inc. | Etherlipid-containing multiple lipid liposomes |
| US6667053B1 (en) | 1996-02-16 | 2003-12-23 | Elan Pharmaceuticals, Inc. | D and L etherlipid stereoisomers and liposomes |
| USRE39042E1 (en) * | 1996-02-16 | 2006-03-28 | The Liposome Company, Inc. | Etherlipid-containing multiple lipid liposomes |
| WO2008074572A1 (en) * | 2006-12-20 | 2008-06-26 | Universitätsklinikum Hamburg-Eppendorf | Use of tri-substituted glycerol compounds for the treatment of hematological malignancies |
| RU2474427C2 (en) * | 2006-12-20 | 2013-02-10 | Универзитетсклиникум Хамбург-Эппендорф | Use of tri-substituted glycerol compounds for treating hematological malignant tumours |
Also Published As
| Publication number | Publication date |
|---|---|
| LU77248A1 (en) | 1977-12-13 |
| IL51988A (en) | 1981-05-20 |
| CA1094455A (en) | 1981-01-27 |
| 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 |
| BE854270A (en) | 1977-11-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed [section 19, patents act 1949] | ||
| PE20 | Patent expired after termination of 20 years |
Effective date: 19970502 |