EP0409845A1 - Methode de protection contre les effets secondaires de la chimiotherapie - Google Patents
Methode de protection contre les effets secondaires de la chimiotherapieInfo
- Publication number
- EP0409845A1 EP0409845A1 EP89902904A EP89902904A EP0409845A1 EP 0409845 A1 EP0409845 A1 EP 0409845A1 EP 89902904 A EP89902904 A EP 89902904A EP 89902904 A EP89902904 A EP 89902904A EP 0409845 A1 EP0409845 A1 EP 0409845A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- derivative
- aminopropylamino
- ethyl dihydrogen
- dihydrogen phosphorothioate
- patient
- 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.)
- Withdrawn
Links
- 230000000694 effects Effects 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims description 35
- 230000000973 chemotherapeutic effect Effects 0.000 title 1
- 210000001185 bone marrow Anatomy 0.000 claims abstract description 8
- 231100000331 toxic Toxicity 0.000 claims abstract description 8
- 230000002588 toxic effect Effects 0.000 claims abstract description 8
- 238000002512 chemotherapy Methods 0.000 claims abstract description 7
- OJZGWRZUOHSWMB-UHFFFAOYSA-N ethoxy-dihydroxy-sulfanylidene-$l^{5}-phosphane Chemical compound CCOP(O)(O)=S OJZGWRZUOHSWMB-UHFFFAOYSA-N 0.000 claims description 37
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 20
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 15
- 229960004857 mitomycin Drugs 0.000 claims description 12
- 229930192392 Mitomycin Natural products 0.000 claims description 11
- 229960004679 doxorubicin Drugs 0.000 claims description 9
- 229960004562 carboplatin Drugs 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 238000001802 infusion Methods 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 5
- HRHKSTOGXBBQCB-UHFFFAOYSA-N Mitomycin E Natural products O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 claims description 3
- 231100000457 cardiotoxic Toxicity 0.000 claims description 3
- 230000001451 cardiotoxic effect Effects 0.000 claims description 3
- HRHKSTOGXBBQCB-VFWICMBZSA-N methylmitomycin Chemical compound O=C1C(N)=C(C)C(=O)C2=C1[C@@H](COC(N)=O)[C@@]1(OC)[C@H]3N(C)[C@H]3CN12 HRHKSTOGXBBQCB-VFWICMBZSA-N 0.000 claims description 3
- UZUUQCBCWDBYCG-UHFFFAOYSA-N Mitomycin B Natural products O=C1C(OC)=C(C)C(=O)C2=C1C(COC(N)=O)C1(O)N2CC2C1N2C UZUUQCBCWDBYCG-UHFFFAOYSA-N 0.000 claims description 2
- HYFMSAFINFJTFH-UHFFFAOYSA-N Mitomycin-A Natural products O=C1C(OC)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)N2CC2NC21 HYFMSAFINFJTFH-UHFFFAOYSA-N 0.000 claims description 2
- HYFMSAFINFJTFH-NGSRAFSJSA-N mitomycin A Chemical compound O=C1C(OC)=C(C)C(=O)C2=C1[C@@H](COC(N)=O)[C@]1(OC)N2C[C@@H]2N[C@@H]21 HYFMSAFINFJTFH-NGSRAFSJSA-N 0.000 claims description 2
- UZUUQCBCWDBYCG-DQRAMIIBSA-N mitomycin B Chemical compound O=C1C(OC)=C(C)C(=O)C2=C1[C@H](COC(N)=O)[C@]1(O)N2C[C@H]2[C@@H]1N2C UZUUQCBCWDBYCG-DQRAMIIBSA-N 0.000 claims description 2
- 190000008236 carboplatin Chemical compound 0.000 claims 3
- 239000002246 antineoplastic agent Substances 0.000 abstract description 11
- 229940127089 cytotoxic agent Drugs 0.000 abstract description 11
- 150000001875 compounds Chemical class 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 206010051779 Bone marrow toxicity Diseases 0.000 description 6
- 231100000366 bone marrow toxicity Toxicity 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 4
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 206010048610 Cardiotoxicity Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 231100000259 cardiotoxicity Toxicity 0.000 description 3
- 230000007681 cardiovascular toxicity Effects 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- QJWQDMBGXNKPAS-UHFFFAOYSA-N 3-azaniumylpropyl(2-bromoethyl)azanium;dibromide Chemical compound Br.Br.NCCCNCCBr QJWQDMBGXNKPAS-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 239000008156 Ringer's lactate solution Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000008366 buffered solution Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- GHKSKVKCKMGRDU-UHFFFAOYSA-N 2-(3-aminopropylamino)ethanol Chemical compound NCCCNCCO GHKSKVKCKMGRDU-UHFFFAOYSA-N 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- -1 alkali metal salts Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- HEWFVANJFLNICL-UHFFFAOYSA-N ethoxy-dihydroxy-sulfanylidene-lambda5-phosphane hydrate Chemical compound O.CCOP(O)(O)=S HEWFVANJFLNICL-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 229950004406 porfiromycin Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- RIFYBBXGYKFBFC-UHFFFAOYSA-K trisodium;thiophosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=S RIFYBBXGYKFBFC-UHFFFAOYSA-K 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- Chemotherapy is one of the most useful treatments available to present day medicine in the struggle against cancer.
- chemotherapeutic agents powerful alkylating agents, antibiotics and platinum-containing compounds have found wide use through the treatment of a variety of cancers.
- doxorubicin and its derivatives can cause cardiac toxicity and bone marrow toxicity.
- the mitomycin family and platinum-containing compounds such as carboplatin can cause bone marrow toxicity in a patient.
- the amount and frequency of chemotherapeutic agent administration may be limited to levels which are below the optimum level for treatment of the cancer from which the patient suffers.
- Doxorubicin (and derivatives such as the hydrochloride derivative, sold under the name ADRIAMYCIN) presently is administered in chemotherapy about once every 3 to 4 weeks in an amount of about 25 to 100 mg/m 2 patient surface area.
- the dosage is commonly about 60 mg/m 2 .
- the frequency and amount of the agent administered is limited because of the cardiotoxic and bone marrow toxic side effects associated with its administration.
- mitomycin family which includes mitomycin A, mitomycin B, mitomycin C and N-methyl mitomycin C (porfiromycin).
- Mitomycin C for example, is presently administered about once every 4 to 6 weeks in amounts of about 5 to 30 mg/m 2 , usually about 10 mg/m 2 .
- the frequency and amount administered is limited due to the bone marrow toxicity associated with administration of the mitomycins.
- Carboplatin a second generation analog of cisplatin (both from Bristol-Myers), is administered about once every 3 to 4 weeks in amounts of about 200-800 mg/m 2 , normally about 400 mg/m 2 .
- the frequency and amount administered is limited due to the bone marrow toxicity associated with carboplatin administration.
- This invention protects a patient against the undesired side effects of the chemotherapeutic agents without significant damage to the beneficial therapeutic properties of the chemotherapeutic agents through the administration of S -2 - ( 3 -aminopr opylamino) ethyl dihydrogen phosphorothioate (and pharmaceutically acceptable derivatives thereof) in an amount sufficient to protect the patient against the cardiac toxicity and/or bone marrow toxicity discussed above.
- S-2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate has the structural formula:
- S-2-(3- aminopropylamino) ethyl dihydrogen phosphorothioate but also to pharmaceutically acceptable derivatives such as alkali metal salts and hydrates thereof.
- S-2-(3- aminopropylamino) ethyl dihydrogen phosphorothioate and its derivatives may be prepared in accordance with the methods disclosed in U.S. Patent No. 3,892,824 to Piper et al., the disclosure of which is incorporated herein by reference.
- S-2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate or a pharmaceutically useful derivatives thereof The amount of S-2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate can be from about 300 to 1,000 mg/m 2 , with a dosage of about 740 mg/m 2 being preferred.
- the S -2 -(3-aminopropylamino) ethyl dihydrogen phosphorothioate or its derivative should be administered either with, or more preferably, before administration of the chemotherapeutic agent. Particularly preferred is drip intravenous infusion in a buffered aqueous solution 15 to 30 minutes before administration of the chemotherapeutic agent. Oral administration is also desirable.
- the S-2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate can be stored frozen at low temperatures, e.g., -70°C.
- the I.V. carrier solution may be a buffered solution of 5% dextrose in Ringers lactate, having a pH of about 7.2 to 7.4. This solution can be made by adding 20 cc of 44.9 mEq sodium bicarbonate to 1 liter of 5% dextrose in Ringers lactate.
- 9.3 cc of the solution can be added to a vial containing 500 mg of S-2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate to produce a solution containing 50 mg/cc of S-2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate.
- further buffered solution can be added for a total volume of 50 cc, and the resulting solution can be administered to a patient over a period of about 15 minutes, using a volumetric pump.
- S-2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate binds to normal cells in competition with the chemotherapeutic agent, but not to tumors.
- S-2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate may be taken up by normal cells, but not tumor cells. It thereby protects the normal tissues by then binding with and inactivating the chemotherapeutic agents.
- S-2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate is not taken up by cancerous tissues, it leaves them open to attack by the chemotherapeutic agents. Significant improvement is expected in white blood cell and granulocyte nadirs, as well as duration of nadirs (or time to recovery). This will allow for the safer administration of conventional dosages of carboplatin and mitomycins and for the safer administration of higher clinical dosages. A significant reduction in the damage to cardiac muscle by doxorubicin will also allow for safer administration of higher cumulative clinical doses.
- a solution of 2-(3-aminopropylamino)ethanol (25.0 g. 0.212 mole) in 48 percent hydrobromic acid (200 ml) is distilled until 35 ml of distillate has been collected.
- the solution is refluxed and periodically, more distillate is collected.
- the total volume of distillate removed in 7 distillation periods is 160 ml. or 80 percent of the original volume of 48 percent hydrobromic acid and the time of continuous boiling is approximately 48 hours.
- the residual solution is then evaporated to dryness under reduced pressure with the aid of several added portions of methanol.
- the crystalline residue is thoroughly triturated with acetone, collected, and washed on the funnel with acetone.
- Trisodium phosphorothioate (6.93 g, 38.5 mmoles) is gradually added in small portions with vigorous stirring to water (38 ml) cooled externally by means of a water bath (15o-20°C.).
- N-(2- bromoethyl)-1.3-propanediamine dihydrobromide (13.3 g, 38.8 mmoles).
- N,N-dimethylformamide (19 ml) is added with continued external cooling at 15°-20oC.
- the solution has been stirred at about 20oC for 90 minutes, it is poured into methanol (250 ml), and the mixture is refrigerated at 4oC overnight.
- the white precipitate that formed is collected and pressed as dry as possible on the funnel.
- the damp solid is dissolved in water (40 ml), and the solution is filtered.
- Addition of methanol (250 ml) reprecipitates the product.
- the product is collected and washed on the funnel, first with methanol and finally with ether.
- the white solid is dried in vacuo at room temperature, then exposed to ambient conditions of the laboratory for 5 hours, and bottled under nitrogen and stored in a freezer.
- the yield of S-2-(3-aminopropylamino) ethyl dihydrogen phosphorothioate monohydrate, mp 160°-161°C. dec. is 8.15 g (91%).
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Toxicology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Le S-2-(3-aminopropylamino)éthyl dihydrogéno-phosphorothiotate et des dérivés pharmaceutiquement acceptables de ce composé sont utilisés pour protéger un patient soumis à un traitement chimiothérapique contre les effets secondaires toxiques pour le coeur et pour la moelle osseuse, associés à l'administration d'agents chimiothérapiques.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15910488A | 1988-02-23 | 1988-02-23 | |
| US159104 | 1988-02-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0409845A1 true EP0409845A1 (fr) | 1991-01-30 |
| EP0409845A4 EP0409845A4 (en) | 1991-07-03 |
Family
ID=22571099
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP19890902904 Withdrawn EP0409845A4 (en) | 1988-02-23 | 1989-02-21 | Method for protection from chemotherapeutic side effects |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0409845A4 (fr) |
| JP (1) | JPH03503888A (fr) |
| AU (1) | AU636107B2 (fr) |
| CA (1) | CA1336506C (fr) |
| WO (1) | WO1989007942A1 (fr) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3827974A1 (de) * | 1988-08-18 | 1990-02-22 | Boehringer Mannheim Gmbh | Kombinationspraeparate von proteinkinase-c-inhibitoren mit lipiden, lipid-analoga, cytostatica oder inhibitoren von phospholipasen |
| US5567686A (en) * | 1992-03-13 | 1996-10-22 | Arch Development Corporation | Method for protection against genotoxic mutagenesis |
| US6051563A (en) * | 1997-02-12 | 2000-04-18 | U.S. Bioscience, Inc. | Methods for the administration of amifostine and related compounds |
| US6573253B2 (en) | 1997-02-12 | 2003-06-03 | Medimmune Oncology Inc. | Methods for the administration of amifostine and related compounds |
| US6239119B1 (en) | 1998-04-27 | 2001-05-29 | Medimmune Oncology, Inc. | Topical administration of amifostine and related compounds |
| US6489312B1 (en) | 1999-06-15 | 2002-12-03 | Medimmune Oncology, Inc. | Pharmaceutical formulations comprising aminoalkyl phosphorothioates |
| US7053072B2 (en) | 2001-05-11 | 2006-05-30 | Medimmune Oncology, Inc. | Methods for the administration of amifostine and related compounds |
| CN102260288B (zh) * | 2010-06-08 | 2014-02-26 | 成都大有得药业有限公司 | 一种三水合3-氨基丙基胺乙基硫代磷酸的合成方法 |
| RU2450791C1 (ru) * | 2010-10-18 | 2012-05-20 | Федеральное государственное учреждение "Ростовский научно-исследовательский онкологический институт Федерального агентства по высокотехнологичной медицинской помощи" | Способ определения кардиотоксических осложнений у больных хроническим лимфолейкозом |
| CN104230984B (zh) * | 2013-06-08 | 2017-02-08 | 国药集团国瑞药业有限公司 | 一种三水合3‑氨基丙基胺乙基硫代磷酸的制备方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4656034A (en) * | 1985-05-20 | 1987-04-07 | Survival Technology, Inc. | Absorption enhancing agents |
-
1989
- 1989-02-21 WO PCT/US1989/000624 patent/WO1989007942A1/fr not_active Ceased
- 1989-02-21 JP JP1502696A patent/JPH03503888A/ja active Pending
- 1989-02-21 EP EP19890902904 patent/EP0409845A4/en not_active Withdrawn
- 1989-02-21 AU AU31940/89A patent/AU636107B2/en not_active Expired
- 1989-02-23 CA CA000591907A patent/CA1336506C/fr not_active Expired - Lifetime
Non-Patent Citations (5)
| Title |
|---|
| American Association for Cancer Research Proceedings, Vol. 22, March 1981, page 271, Abstract No. 1075, Washington, DC, US; T.L. PHILLIPS et al.: "Differential protection against cytotoxic chemotherapeutic effects on bone marrow CFUs, intestinal crypt cells, EMT6 tumor", whole article. * |
| Drugs of the Future, Vol. 14, No. 11, November 1989, pages 1105-1107; whole article. * |
| J. Pharmacobio.-Dynamics, Vol. 3, No. 7, July 1980, page s-21; M. ONODA et al.: "Effect of various kinds of drugs in vitro on the proliferation of leukopoietic stem cells (CFU-C)", whole article. * |
| Proceedings of the 9th Annual Conference of the IEEE Engineering in Medicine and Biology Society, Boston, 13th-16th November 1987, pages 1443-1445, New York, US; M.-A. RIX-MONTEL: "Radioprotective effects of thiophosphates", whole article. * |
| See also references of WO8907942A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH03503888A (ja) | 1991-08-29 |
| AU3194089A (en) | 1989-09-22 |
| CA1336506C (fr) | 1995-08-01 |
| WO1989007942A1 (fr) | 1989-09-08 |
| EP0409845A4 (en) | 1991-07-03 |
| AU636107B2 (en) | 1993-04-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR0142907B1 (ko) | 골수억제제 | |
| US4296105A (en) | Derivatives of doxorubicine, their preparation and use | |
| US6537990B1 (en) | Combined preparations comprising morpholine anthracyclines and anticancer agent | |
| GB1583661A (en) | Tumour antidote | |
| JP2714402B2 (ja) | 癌転移抑制剤 | |
| CA1336506C (fr) | Methode de protection contre les effets chimiotherapeutiques | |
| US4066650A (en) | Keto-aldehyde-amine addition products and method of making same | |
| RU2097040C1 (ru) | Применение креатинфосфата для лечения опухолей и фармацевтические препараты, обладающие противоопухолевой активностью | |
| RU2353623C1 (ru) | Корректор цитостатической полихимиотерапии | |
| CA2145229A1 (fr) | Compositions suppressives de metastases hepatiques | |
| NL8100579A (nl) | Toepassing van nooetroop werkzame verbindingen. | |
| EP0768084A1 (fr) | Inhibiteur de la metastase cancereuse | |
| AU2003298077A1 (en) | Proline derivatives used as pharmaceutical active ingredients for the treatment of tumours | |
| FI78069B (fi) | Foerfarande foer framstaellning av saosom laekemedel anvaendbara acylerade enamidfoereningar. | |
| JP2000302762A (ja) | 放射線および化学療法における感受性増強剤であるグリシジアゾール金属塩、並びにそれらの製造方法および使用 | |
| US20080293648A1 (en) | Compositions and Methods for Cancer Treatment | |
| Sugiura | Effect of 1, 3-bis (2-chloroethyl)-1-nitrosourea (NSC-409962) and two related compounds on a spectrum of tumors | |
| EP0432630B1 (fr) | Agent antitumoral | |
| US7732485B2 (en) | Treatment of cancer | |
| US3169091A (en) | Process for inhibiting tumors with substituted pyrazoles | |
| JPS62919B2 (fr) | ||
| US4423076A (en) | 1-Branched-alkyl-3-(2-haloethyl)-3-nitrosoureas as novel antitumor agents | |
| EP0392662B1 (fr) | Utilisation de complexes du tétrachloroplatinate avec un colorant diazoique comme agents anticancéreux | |
| JPS63264580A (ja) | ３−（２−ハロアルキル）−１，４−オキサチインおよび２−（２−ハロアルキル）−１，４−ジチイン | |
| NL8901623A (nl) | Mitomycine-fosfaatderivaten. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 19900823 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
| A4 | Supplementary search report drawn up and despatched |
Effective date: 19910516 |
|
| AK | Designated contracting states |
Kind code of ref document: A4 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
| 17Q | First examination report despatched |
Effective date: 19920305 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 19930513 |