DE3331459A1 - Composition for tumour treatment containing diazoxide, and the use thereof - Google Patents

Composition for tumour treatment containing diazoxide, and the use thereof

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Publication number
DE3331459A1
DE3331459A1 DE19833331459 DE3331459A DE3331459A1 DE 3331459 A1 DE3331459 A1 DE 3331459A1 DE 19833331459 DE19833331459 DE 19833331459 DE 3331459 A DE3331459 A DE 3331459A DE 3331459 A1 DE3331459 A1 DE 3331459A1
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Germany
Prior art keywords
diazoxide
tumor
preparation
composition
treatment containing
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.)
Granted
Application number
DE19833331459
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German (de)
Other versions
DE3331459C2 (en
Inventor
Martin Dr.med. 6900 Heidelberg Berger
Michael Dr.med. 8000 München Fink
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Individual
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Individual
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Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to DE19833331459 priority Critical patent/DE3331459A1/en
Publication of DE3331459A1 publication Critical patent/DE3331459A1/en
Application granted granted Critical
Publication of DE3331459C2 publication Critical patent/DE3331459C2/de
Granted legal-status Critical Current

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone

Abstract

The invention relates to a composition for tumour treatment containing diazoxide, and to the use thereof.

Description

Beschreibung:Description:

In den letzten 15 Jahren wurden drei tierexperimentelle Untersuchungen veriffentlicht, in denen nahezu übereinstimmend ein langsames Wachstum oder eine Remission von Tumoren in diabetischen Versuchstieren beschrieben. wird. Beim DM8A-induzierten %mma-Carcinom der Ratte wurde von Heuson und Legros eine erhebliche Verkleinerung von 90« der Tumoren beschrieben, nachdem bei den Tieren ein Alloxan-Diabetes induziert worden war (Europ.There have been three animal studies in the past 15 years published in which a slow growth or a nearly consistent Remission of tumors in diabetic test animals is described. will. When the DM8A-induced % mma carcinoma in the rat was a substantial reduction in size by Heuson and Legros of 90% of the tumors described after alloxan diabetes was induced in the animals had been (Europ.

J. Cancer 6 (1970),.349). Eine deutliche Reduktion des Tumorwachstums nach Diabetes-Induktion mit Alloxan konnte von Puckett und Shingleton bei einem Mamma-Carcinom der C3H-'1us (Cancer Res. 32 (1972), 789) und von Pavelic beim Methylcholanthren-induzierten Fibrosarkom der Maus (Europ.J. Cancer, 6: 349 (1970)). A significant reduction in tumor growth After diabetes induction with alloxan, von Puckett and Shingleton could in one Mammary carcinoma of C3H-'1us (Cancer Res. 32 (1972), 789) and of Pavelic in the case of methylcholanthrene-induced Mouse fibrosarcoma (Europ.

J. Cancer 16 (1980), 279) beobachtet werden.J. Cancer 16: 279 (1980)).

Die eigentliche biochemische Ursache der erwähnten Remissionsinduktion bzw. Wachstumsverzögerung scheint derzeit noch nicht bekannt zu sein.The actual biochemical cause of the remission induction mentioned or growth retardation does not seem to be known yet.

Umgekehrt ist jedoch die ebenfalls beschriebene und in der Mehrzahl der Fälle gefundene Wachstumsförderung maligner Tumoren durch Insulin wahrscheinlich nicht durch einen metabolischen Effekt, sondern durch eine Wirkung auf das DNS-produzierende Enzym-System bedingt (Heuson und Legros: Cancer Res. 31 (1971), 59).However, the reverse is also described and in the majority of the cases found, growth of malignant tumors is likely to be promoted by insulin not by a metabolic effect, but by an effect on the DNA-producing one Due to the enzyme system (Heuson and Legros: Cancer Res. 31 (1971), 59).

Auch beim Menschen scheint ein Diabetes mellitus einen günstigeren Verlauf des metastasierenden Mamma-Carcinoms zu bewirken. Rhomberg fand bei diabetischen Mamma-Carcinam-Patientinnen eindeutig g längere Oberlebenszeiten sowie ein Ansprechen auf verschiedene Formen der Hormontherapie in 18 von 24 Fällen gegenüber ca. 30«, bei den übrigen Patientinnen (Dtsch. Med.Diabetes mellitus also appears to be more favorable in humans To effect the course of the metastatic breast carcinoma. Rhomberg found in diabetic Mamma carcinam patients clearly had longer survival times and a response on different forms of hormone therapy in 18 of 24 cases compared to approx. 30 «, in the other patients (German Med.

Wschr. 100 (1975), 2422). Der Schluß scheint somit zulässig, daß Versuche am DMBA-induzierten Mamma-Carcinom der Ratte einen Vergleich mit der menschlichen Situation ermöglichen.Wschr. 100: 2422 (1975)). The conclusion thus seems admissible that experiments in the DMBA-induced mammary carcinoma of the rat a comparison with that of humans Enable situation.

Durch tierexperimentelle Untersuchungen kann als gesichert gelten, daß verschiedene Tumoren nach Diabetes-Induktion ein verlangsamtes Wachstum zeigen oder in Remission gehen.Animal experiments can be considered to be certain that various tumors show slowed growth after the induction of diabetes or go into remission.

Dieser Effekt ist besonders gut für das DMBA-induzierte Mamma-Carcinom der Ratte nach Diabetes-Induktion mit Alloxan belegt (Literatur siehe 2.2).This effect is particularly good for DMBA-induced breast carcinoma the rat covered with alloxan after induction of diabetes (for literature see 2.2).

Der irreversible Alloxan-Diabetes ist zur Therapie menschlicher Tumoren nicht geeignet. Möglich wäre jedoch eine Behandlung mit Diazoxid, das ohne wesentliche Nebenwirkungen einen reversiblen Diabetes induziert (Kühnau und Martin, DMl; 79 (1972), 1870). Dieses Benzothiadiazinderivat findet bisher als Antihypoklämikum therapeutische Anwendung und wird auch bei maligner Hypertonie eingesetzt; es hemmt die Sekretion von Insulin aus den ß-Zellsn der Pankreas-Inseln.The irreversible alloxan diabetes is used to treat human tumors not suitable. A treatment with diazoxide would be possible, however, without essential Side effects induce reversible diabetes (Kühnau and Martin, DMl; 79 (1972), 1870). This benzothiadiazine derivative has so far been used as an antihypoclemic therapeutic application and is also used in malignant hypertension; it inhibits the secretion of insulin from the ß-cells of the pancreatic islets.

Erfindungsgemäß wurde nun festgestellt, daß im Tierversuch eine Therapie des DtABA-induzierten Mamma-Carcinoms mit Diazoxid das Tumorwachstum signifikant mindert, so daß sich die Möglichkeit anbietet, diesen Wirkstoff in der Behandlung menschlicher Tumoren zu erproben.According to the invention it has now been found that a therapy in animal experiments of DtABA-induced breast carcinoma with diazoxide significantly increased tumor growth reduces, so that there is the possibility of using this active ingredient in the treatment to test human tumors.

Es wurde außerdem festgestellt, daß die Remissionsdauer a-nsteigt, wenn Diazoxid mit Tamoxifen kombiniert wird. In der Kombination von Diazoxid mit Medroxyprogesteron-acetat steigt die Remissionsquote zwar an, die Remissionsdauer sinkt jedoch.It was also found that the remission duration a-n increases, when diazoxide is combined with tamoxifen. In the combination of diazoxide with Medroxyprogesterone acetate increases the remission rate and the duration of remission however, it sinks.

Die Erfindung wird durch die Patentansprüche näher gekennzeichnet und durch die folgenden Versuche belegt.The invention is further characterized by the claims and evidenced by the following experiments.

Dabei wird die Remission als die Verminderung des Tumorvolumens auf unter 50 % des Ausgangswertes definiert.Thereby the remission is based on the reduction of the tumor volume defined below 50% of the initial value.

Claims (4)

Zubereitung zur Tumorbehandlung mit einem Gehalt an Diazoxid und dessen Verwendung Patentansprüche: 1. Zubereitung zur Tumor- und insbesondere Mammacarcinombehandlung mit einem Gehalt an Diazoxid und gegebenenfalls üblichen Hilfs- und/oder Trägermitteln, g e k e n n -z e i c h n e t durch a) ein pufferndes basisches Hilfsmittel und/oder b) ein pharmazeutisch verträgliches Diazoxid-Lösungsmittel und gegebenenfalls einen Emulgator für Wasser-Lösungsmittel-Emulsionen und/oder c) gegebenenfalls Tamoxifen oder Medroxyprogesteron-acetat und/oder d) einen oder mehrere andere hormonelle oder antihormonelle TUmorwachstum hemmende Wirkstoffe.Preparation for tumor treatment with a content of diazoxide and its Use of claims: 1. Preparation for tumor and especially breast cancer treatment With a content of diazoxide and, if necessary, customary auxiliaries and / or carriers, g e k e n n -z e i c h n e t by a) a buffering basic aid and / or b) a pharmaceutically acceptable diazoxide solvent and optionally one Emulsifier for water-solvent emulsions and / or c) optionally tamoxifen or medroxyprogesterone acetate and / or d) one or more other hormonal ones or anti-hormonal tumor growth inhibiting agents. 2 Zubereitung nach Anspruch 1, g e k e n n z e i c h n e t durch eine oral applizierte Konfektionierung.2 Preparation according to claim 1, g e k e n n n z e i c h n e t by a orally applied packaging. 3. Verwendung von Diazoxid, gegebenenfalls in Kombination mit Tamoxifen oder Medroxyprogesteron-acetat, zur Tumor-, Leukamie- und insbesondere Mammacarcinombehandlung.3. Use of diazoxide, possibly in combination with tamoxifen or medroxyprogesterone acetate, for tumor, leukemia and especially breast cancer treatment. 4. Verwendung nach Anspruch 3 für Zurbereitungen gemäß Anspruch 1 oder 2, insbesondere zu deren Herstellung, wie Konfektionierung, Formulierung, Dosierung und Veroackuno.4. Use according to claim 3 for preparations according to claim 1 or 2, in particular for their production, such as packaging, formulation, dosing and Veroackuno.
DE19833331459 1982-08-31 1983-08-31 Composition for tumour treatment containing diazoxide, and the use thereof Granted DE3331459A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE19833331459 DE3331459A1 (en) 1982-08-31 1983-08-31 Composition for tumour treatment containing diazoxide, and the use thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3232374 1982-08-31
DE19833331459 DE3331459A1 (en) 1982-08-31 1983-08-31 Composition for tumour treatment containing diazoxide, and the use thereof

Publications (2)

Publication Number Publication Date
DE3331459A1 true DE3331459A1 (en) 1984-03-01
DE3331459C2 DE3331459C2 (en) 1992-02-13

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DE (1) DE3331459A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993011757A1 (en) * 1991-12-10 1993-06-24 Orion-Yhtymä Oy Drug formulations for parenteral use
WO1998049146A2 (en) * 1997-04-28 1998-11-05 The United States Of America, Represented By The Secretary Department Of Health & Human Services, The National Institutes Of Health Cyclin dependent kinase (cdk)4 inhibitors and their use for treating cancer
EP1850663A2 (en) * 2005-02-22 2007-11-07 Cedars-Sinai Medical Center Use of minoxidil sulfate as an anti-tumor drug

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Chem. Abstr. 70, 19, Nr. 85974 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993011757A1 (en) * 1991-12-10 1993-06-24 Orion-Yhtymä Oy Drug formulations for parenteral use
US5571534A (en) * 1991-12-10 1996-11-05 Orion-Yhtyma Oy Drug formulations for parenteral use
WO1998049146A2 (en) * 1997-04-28 1998-11-05 The United States Of America, Represented By The Secretary Department Of Health & Human Services, The National Institutes Of Health Cyclin dependent kinase (cdk)4 inhibitors and their use for treating cancer
WO1998049146A3 (en) * 1997-04-28 1999-08-12 Us Health Cyclin dependent kinase (cdk)4 inhibitors and their use for treating cancer
EP1850663A2 (en) * 2005-02-22 2007-11-07 Cedars-Sinai Medical Center Use of minoxidil sulfate as an anti-tumor drug
EP1850663A4 (en) * 2005-02-22 2008-03-19 Cedars Sinai Medical Center Use of minoxidil sulfate as an anti-tumor drug
US7705010B2 (en) 2005-02-22 2010-04-27 Cedars-Sinai Medical Center Use of minoxidil sulfate as an anti-tumor drug

Also Published As

Publication number Publication date
DE3331459C2 (en) 1992-02-13

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