DE3638124A1 - Novel pharmaceutical use of ebselen - Google Patents
Novel pharmaceutical use of ebselenInfo
- Publication number
- DE3638124A1 DE3638124A1 DE19863638124 DE3638124A DE3638124A1 DE 3638124 A1 DE3638124 A1 DE 3638124A1 DE 19863638124 DE19863638124 DE 19863638124 DE 3638124 A DE3638124 A DE 3638124A DE 3638124 A1 DE3638124 A1 DE 3638124A1
- Authority
- DE
- Germany
- Prior art keywords
- ebselen
- pharmaceutical use
- novel pharmaceutical
- tumors
- animals
- 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
Links
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
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Die Erfindung betrifft eine neue Verwendung von Ebselen zur Therapie von malignen Neoplasien und die diesen Wirkstoff enthaltenden pharmazeutischen Zubereitungen, bzw. die Verwendung dieser Verbindung zur Herstellung von Arzneimitteln zur Behandlung von Krebserkrankungen.The invention relates to a new use of Ebselen for the therapy of malignant neoplasms and this active ingredient containing pharmaceutical preparations, or the use of this compound to produce Medicines used to treat cancer.
Die Entwicklung von Substanzen zur Behandlung von malignen Neoplasien, die in die großen Untergruppen Carcinome, Sarkome, Leukämien und Tumoren eingeteilt werden, ist in den letzten Jahrzehnten lawinenartig angewachsen, wobei eine Vielzahl von Verbindungen synthetisiert und alle nur erdenklichen chemischen Körperklassen hinsichtlich ihrer tumorhemmenden Eigenschaften untersucht wurden. Bei keiner der bisher bekannten Substanzen handelt es sich aber um einen spezifisch gegen den Krebs gerichteten Wirkstoff, sondern um Verbindungen, die in irgendeiner Weise einen allgemein toxischen Effekt auf Zellen entfalten und so daß Zellwachstum hemmen. Die Krebszellen werden im allgemeinen durch diese Zytostatika nur deshalb stärker geschädigt, weil sie eine höhere Wachstums- bzw. Proliferationsrate und damit eine erhöhte Nucleoprotein-Synthese und stärkere Glykolyse als normale Zellen besitzen. Die unspezifische Wirkung erklärt aber auch die toxischen Nebenerscheinungen dieser Verbindungen auf andere Proliferationsgewebe des Organismus, so daß ein echtes Heilmittel immer noch aussteht.The development of substances for the treatment of malignancies Neoplasms that fall into the large subgroups carcinomas, Sarcomas, leukemias and tumors are classified into has grown like an avalanche in recent decades, with a variety of compounds are synthesized and all only imaginable chemical body classes with regard to their tumor-inhibiting properties were examined. With none of the substances known so far, however an anti-cancer drug but about connections in some way develop a generally toxic effect on cells and so that inhibit cell growth. The cancer cells are in the general because of these cytostatics only stronger damaged because they have a higher growth or proliferation rate and thus an increased nucleoprotein synthesis and have stronger glycolysis than normal cells. The non-specific effects also explain the toxic effects Side effects of these connections on other proliferation tissues of the organism, making it a real remedy still pending.
Es wurde nun überraschend gefunden, daß Ebselen eine sehr spezifische tumorhemmende Wirksamkeit zeigt.It has now surprisingly been found that Ebselen is a very shows specific anti-tumor activity.
Ebselen (2-Phenyl-1,2-benzisoselenazol-3(2H)-on/INN- Liste No. 51) ist eine bekannte Verbindung, die zur Behandlung von rheumatischen Erkrankungen eingesetzt werden kann (DE-PS 30 27 073) und z. B. nach dem Verfahren von R. Weber, M. Renson, Bulletin de la Soc. Chim. de France 1976 (7/8), 1124-1126, durch Reaktion von 2- Methylseleno-N-phenyl-benzamid mit Phosphorpentachlorid und anschließender Hydrolyse hergestellt wird. Besonders hervorzuheben ist die gute Verträglichkeit dieser Substanz, da Ebselen mit einer LD₅₀ von ≧ 4600 mg/kg p. o. (Ratte) praktisch untoxisch ist.Ebselen (2-phenyl-1,2-benzisoselenazol-3 (2H) -one / INN- List No. 51) is a known compound used for Treatment of rheumatic diseases used can be (DE-PS 30 27 073) and z. B. after the procedure by R. Weber, M. Renson, Bulletin de la Soc. Chim. de France 1976 (7/8), 1124-1126, by reaction of 2- Methylseleno-N-phenyl-benzamide with phosphorus pentachloride and subsequent hydrolysis is produced. Especially the good tolerability of these should be emphasized Substance since Ebselen with an LD₅₀ of ≧ 4600 mg / kg p. o. (rat) is practically non-toxic.
Die überraschende Antitumor-Wirksamkeit von Ebselen wurde in dem von J. G. Liehr et al. entwickelten Modell gefunden (J. G. Liehr, D. E. Sirdasku, "Estrogen dependent kidney tumors" Vol. 11, Tissue culture of epithelium cells, Ed. Marie Taub, Plenum Publ. corp. 1985, S. 205-234).The surprising anti-tumor efficacy of Ebselen has been demonstrated in the study by J.G. Liehr et al. developed model found (J.G. Liehr, D.E. Sirdasku, "Estrogen dependent kidney tumors "Vol. 11, Tissue culture of epithelium cells, Ed. Marie Taub, Plenum Publ. Corp. 1985, pp. 205-234).
Dabei wurden 4-6 Wochen alte männliche syrische Hamster
mit einem subkutanen Estradiol-Implantat (90% Estradiol
und 10% Cholesterol) behandelt. Diese Estrogen-behandelten
Tiere und unbehandelten Hamster wurden in 4 Gruppen
aufgeteilt, wie der Tabelle I zu entnehmen ist. Die mit
Ebselen behandelten Tiere erhielten Nagetierfutter, dem
auf das Trockengewicht bezogen 0,15% Ebselen zugesetzt
war (ca. 105 mg/kg). Diese Diät wurde mit Wasser versetzt,
um eine Brei-Konsistenz zu erhalten. Nach 3 Monaten
wurde den Estrogen-behandelten Tieren ein zusätzliches
Implantat gleichen Gewichts und gleicher Zusammensetzung
appliziert. Nach 196 Tagen wurden die Tiere getötet
und die Nieren und andere Organe entnommen. Die Nieren
wurden der Länge nach geteilt. Eine Hälfte jeder Niere
und ein Teil anderer Organe wurden zur mikroskopisch-
histologischen Untersuchung in Formalin gelegt. Bei grober
Überprüfung makroskopisch sichtbare Tumoren sind in
Tabelle I aufgeführt.
BehandlungZahl der Tiere mit
(Zahl der Tiere)Tumoren (Zahl der
geprüften Tiere)
unbehandelt (5)0 (5)
Estradiol (5)5 (5)
Estradiol+Ebselen (5)1 (5)
Ebselen (5)0 (5)Male Syrian hamsters 4-6 weeks old were treated with a subcutaneous estradiol implant (90% estradiol and 10% cholesterol). These estrogen-treated animals and untreated hamsters were divided into 4 groups, as can be seen in Table I. The animals treated with Ebselen received rodent feed, to which 0.15% Ebselen was added (approx. 105 mg / kg) based on the dry weight. Water was added to this diet to maintain a porridge consistency. After 3 months, the estrogen-treated animals were given an additional implant of the same weight and composition. After 196 days, the animals were sacrificed and the kidneys and other organs removed. The kidneys were divided lengthways. Half of each kidney and part of other organs were placed in formalin for microscopic histological examination. In rough examination, macroscopically visible tumors are listed in Table I.
TreatmentNumber of animals with (number of animals) tumors (number of
animals tested) untreated (5) 0 (5) estradiol (5) 5 (5) estradiol + Ebselen (5) 1 (5) Ebselen (5) 0 (5)
Aus diesem Versuch wird ersichtlich, daß Ebselen eine sehr spezifische Wirkung bei der Behandlung von Tumoren entwickelt. Da Induktionstumoren sich gegenüber Zytostatika normalerweise wesentlich unempfindlicher als Transplantationstumoren verhalten, ist dies als vorteilhaft für die Beurteilung der Erfolgschancen am Menschen anzusehen, zumal der gesamte Ablauf der Tumorentwicklung viel mehr den Vorgängen beim Menschen ähnelt.From this experiment it can be seen that Ebselen is a very specific effect in the treatment of tumors developed. Because induction tumors differ from cytostatics usually much less sensitive than transplant tumors behavior, this is advantageous for assessing the chances of success in humans, especially since the entire course of tumor development is a lot more like human processes.
Die vorliegende Erfindung betrifft ebenfalls pharmazeutische Präparate, welche als Wirkstoff Ebselen enthalten. Bei den erfindungsgemäßen pharmazeutischen Präparaten handelt es sich um solche zur enteralen wie oralen oder rektalen sowie parenteralen Verabreichung, welche den pharmazeutischen Wirkstoff allein oder zusammen mit einem üblichen, pharmazeutischen anwendbaren Trägermaterial enthalten. Vorteilhafterweise liegt die pharmazeutische Zubereitung des Wirkstoffes in Form von Einzeldosen vor, die auf die gewünschte Verabreichung abgestimmt sind, z. B. Tabletten, Drag´es, Kapseln, Suppositorien, Granulate, Lösungen, Emulsionen oder Suspensionen. Die Dosierung der Substanz liegt üblicherweise zwischen 10 und 2000 mg pro Tag, vorzugsweise zwischen 30 und 300 mg pro Tag, und kann in einer Dosis oder mehreren Teildosen, vorzugsweise in zwei bis drei Teildosen pro Tag, verabreicht werden. Die Herstellung der erfindungsgemäßen Arzneimittel wird durch die folgenden Beispiele näher erläutert.The present invention also relates to pharmaceutical Preparations containing Ebselen as the active ingredient. In the pharmaceutical preparations according to the invention are they enteral or oral? rectal and parenteral administration, which the active pharmaceutical ingredient alone or together with a contain customary, pharmaceutically applicable carrier material. The pharmaceutical is advantageously located Preparation of the active ingredient in the form of single doses, which are tailored to the desired administration, e.g. B. tablets, drages, capsules, suppositories, granules, Solutions, emulsions or suspensions. The dosage the substance is usually between 10 and 2000 mg per day, preferably between 30 and 300 mg per day, and may be in one or more divided doses, preferably in two to three divided doses per day. The preparation of the pharmaceuticals according to the invention is explained in more detail by the following examples.
Nach bekannten Verfahren hergestellte pharmazeutische
Form des erfindungsgemäßen Arzneimittels.
Tabletten zu 500 mg mit einem Wirkstoffgehalt von 150 mg.Pharmaceutical form of the medicament according to the invention produced by known processes.
500 mg tablets with an active substance content of 150 mg.
Ebselen150 mg Lactose250 mg kristalline Cellulose 50 mg Calciumcarboxymethylcellulose 30 mg Magnesiumstearat 20 mgEbselen 150 mg Lactose 250 mg crystalline cellulose 50 mg Calcium carboxymethyl cellulose 30 mg Magnesium stearate 20 mg
Nach bekannten Verfahren hergestellte pharmazeutische
Form des erfindungsgemäßen Arzneimittels.
Tabletten zu 300 mg mit einem Wirkstoffgehalt von 100 mg.Pharmaceutical form of the medicament according to the invention produced by known processes.
300 mg tablets with an active ingredient content of 100 mg.
Ebselen100 mg mikrokristalline Cellulose150 mg Cutina® HR 20 mg Hydroxypropylmethylcellulosephthalat 30 mgEbselen 100 mg microcrystalline cellulose 150 mg Cutina® HR 20 mg Hydroxypropyl methyl cellulose phthalate 30 mg
Nach bekannten Verfahren hergestellte pharmazeutische
Form des erfindungsgemäßen Arzneimittels.
Kapseln mit einem Wirkstoffgehalt von 50 mg.Pharmaceutical form of the medicament according to the invention produced by known processes.
Capsules with an active ingredient content of 50 mg.
Ebselen 50 mg Lactose100 mg kristalline Cellulose 45 mg kolloidales Siliciumdioxid 5 mgEbselen 50 mg Lactose 100 mg crystalline cellulose 45 mg colloidal silicon dioxide 5 mg
Claims (3)
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE3638124A DE3638124C2 (en) | 1986-11-08 | 1986-11-08 | New pharmaceutical use of Ebselen |
KR1019870012297A KR950008767B1 (en) | 1986-11-08 | 1987-11-03 | Novel pharmacentical use of ebselen |
JP62279414A JPH0625059B2 (en) | 1986-11-08 | 1987-11-06 | Malignant tumor therapeutic agent |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE3638124A DE3638124C2 (en) | 1986-11-08 | 1986-11-08 | New pharmaceutical use of Ebselen |
Publications (2)
Publication Number | Publication Date |
---|---|
DE3638124A1 true DE3638124A1 (en) | 1988-05-11 |
DE3638124C2 DE3638124C2 (en) | 1996-09-05 |
Family
ID=6313486
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE3638124A Expired - Lifetime DE3638124C2 (en) | 1986-11-08 | 1986-11-08 | New pharmaceutical use of Ebselen |
Country Status (3)
Country | Link |
---|---|
JP (1) | JPH0625059B2 (en) |
KR (1) | KR950008767B1 (en) |
DE (1) | DE3638124C2 (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992002221A1 (en) * | 1990-08-06 | 1992-02-20 | Rhone-Poulenc Rorer Gmbh | Use of 2-phenyl-1,2-benzisoselenazol-3(2h)-one |
WO2000001380A1 (en) * | 1998-07-01 | 2000-01-13 | A. Nattermann & Cie. Gmbh | cyclo-oxygenase inhibitor |
AU725534B2 (en) * | 1996-08-27 | 2000-10-12 | A. Nattermann & Cie Gmbh | Preventive or therapeutic drug for Alzheimer's disease |
EP1174423A1 (en) * | 1999-03-31 | 2002-01-23 | Daiichi Pharmaceutical Co., Ltd. | Substrates for thioredoxin reductase |
EP1855662A2 (en) * | 2005-03-08 | 2007-11-21 | Sound Pharmaceuticals Incorporated | Methods and compositions for treating cancer |
US7820640B2 (en) | 2002-01-04 | 2010-10-26 | Sound Pharmaceuticals Incorporated | Methods for treating hearing loss |
US8309560B2 (en) | 2001-11-29 | 2012-11-13 | Sound Pharmaceuticals Incorporated | Methods and compositions for ameliorating the undesirable effects of chemotherapy |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996033712A1 (en) * | 1995-04-25 | 1996-10-31 | Daiichi Pharmaceutical Co., Ltd. | Remedy for acquired immunodeficiency syndrome |
CN1166651C (en) * | 2001-06-08 | 2004-09-15 | 北京大学药学院 | Anti-inflammatory and antineoplastic R-bis or glycophenylpropane isoselenazole substituted compound |
DE10343521A1 (en) * | 2003-09-19 | 2005-04-21 | Beru Ag | Pressure measuring glow plug for a diesel engine |
JP5435461B2 (en) * | 2009-06-04 | 2014-03-05 | 国立大学法人群馬大学 | Migration inhibitor for cancer treatment |
US10058542B1 (en) | 2014-09-12 | 2018-08-28 | Thioredoxin Systems Ab | Composition comprising selenazol or thiazolone derivatives and silver and method of treatment therewith |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3027073C2 (en) * | 1980-07-17 | 1985-03-07 | A. Nattermann & Cie GmbH, 5000 Köln | Pharmaceutical preparations containing 2-phenyl-1,2-benzisoselenazol-3 (2H) -one |
-
1986
- 1986-11-08 DE DE3638124A patent/DE3638124C2/en not_active Expired - Lifetime
-
1987
- 1987-11-03 KR KR1019870012297A patent/KR950008767B1/en not_active IP Right Cessation
- 1987-11-06 JP JP62279414A patent/JPH0625059B2/en not_active Expired - Lifetime
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3027073C2 (en) * | 1980-07-17 | 1985-03-07 | A. Nattermann & Cie GmbH, 5000 Köln | Pharmaceutical preparations containing 2-phenyl-1,2-benzisoselenazol-3 (2H) -one |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992002221A1 (en) * | 1990-08-06 | 1992-02-20 | Rhone-Poulenc Rorer Gmbh | Use of 2-phenyl-1,2-benzisoselenazol-3(2h)-one |
AU725534B2 (en) * | 1996-08-27 | 2000-10-12 | A. Nattermann & Cie Gmbh | Preventive or therapeutic drug for Alzheimer's disease |
US6495517B2 (en) | 1998-07-01 | 2002-12-17 | A. Natterman & Cie. Gmbh | Cyclooxygenase inhibitor |
EP0972515A3 (en) * | 1998-07-01 | 2000-01-26 | A. Nattermann & Cie. GmbH | Cyclooxygenase Inhibitor |
EP0972515A2 (en) * | 1998-07-01 | 2000-01-19 | A. Nattermann & Cie. GmbH | Cyclooxygenase Inhibitor |
WO2000001380A1 (en) * | 1998-07-01 | 2000-01-13 | A. Nattermann & Cie. Gmbh | cyclo-oxygenase inhibitor |
EP1174423A1 (en) * | 1999-03-31 | 2002-01-23 | Daiichi Pharmaceutical Co., Ltd. | Substrates for thioredoxin reductase |
EP1174423A4 (en) * | 1999-03-31 | 2008-03-19 | Arne Holmgren | Substrates for thioredoxin reductase |
US7671211B1 (en) | 1999-03-31 | 2010-03-02 | Arne Holmgren | Substrates for thioredoxin reductase |
US8309560B2 (en) | 2001-11-29 | 2012-11-13 | Sound Pharmaceuticals Incorporated | Methods and compositions for ameliorating the undesirable effects of chemotherapy |
US7820640B2 (en) | 2002-01-04 | 2010-10-26 | Sound Pharmaceuticals Incorporated | Methods for treating hearing loss |
EP1855662A2 (en) * | 2005-03-08 | 2007-11-21 | Sound Pharmaceuticals Incorporated | Methods and compositions for treating cancer |
EP1855662A4 (en) * | 2005-03-08 | 2009-12-23 | Sound Pharmaceuticals Inc | Methods and compositions for treating cancer |
Also Published As
Publication number | Publication date |
---|---|
JPH0625059B2 (en) | 1994-04-06 |
KR950008767B1 (en) | 1995-08-08 |
JPS63183528A (en) | 1988-07-28 |
KR880005928A (en) | 1988-07-21 |
DE3638124C2 (en) | 1996-09-05 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
8110 | Request for examination paragraph 44 | ||
8125 | Change of the main classification |
Ipc: A61K 31/41 |
|
D2 | Grant after examination | ||
8364 | No opposition during term of opposition |