GB2141930A - Novel pharmaceutical preparations with anti-tumour effect - Google Patents
Novel pharmaceutical preparations with anti-tumour effect Download PDFInfo
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- GB2141930A GB2141930A GB08415453A GB8415453A GB2141930A GB 2141930 A GB2141930 A GB 2141930A GB 08415453 A GB08415453 A GB 08415453A GB 8415453 A GB8415453 A GB 8415453A GB 2141930 A GB2141930 A GB 2141930A
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- preparation
- valepotriate
- valepotriates
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- weight
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- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- 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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- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Description
SPECIFICATION
Novel Pharmaceutical Preparations with Anti
Tumour Effect
This invention relates to the use of valepotriates for prophylaxis and treatment of tumour growth in mammals and humans, and also relates to pharmaceutical preparations for the treatment of tumours in humans and mammals, which preparations contain valepotriates as tumour-inhibiting effective substances.
The valepotriates with which the present application is concerned are esters of polyhydroxycyclopenta(c)pyran compounds of the following formula I
in which A and B are each hydrogen or together form a bond and, of the radicals R, to R3, one is isovaleryl, another is acetyl and the third is the acyl radical of one of the following acids: isovaleric acid, p-methyl valeric acid, aisovaleroxyisovaleric acid, a-acetoxyisovaleric acid, p-acetoxyisovaleric acid, p-acetoxy-p-methyl valeric acid or P-hydroxy-isovaleric acid.
The valepotriates are known compounds (see, for example, an article by Thies et al in Planta medica 41, 15-20 (1981)), which describes pharmacologically active components of valerian or of plants of the valerianaceae family or derivatives of such components. The valepotriates are known to have properties which affect the central nervous system, in particular sedative, psychically equilibratory and spasmolytic properties.
The sedative and psychically equilibratory effects of valerian and its components have been used medicinally for a long time. In pharmaceutical preparations for the sedation and equilibration of vegetative and psychic disorders, valerian extracts or valepotriates are usually employed in quantities which correspond to individual doses of 1 to 50 mg valepotriate.
Bounthan et al report in a study (Planta medica 41, 21-28 (1981)) that some valepotriates in in vitro tests showed cytotoxic properties with regard to hepatoma cells and that didrovaltratum showed itself to be effective against experimentally produced cancer-ll-ascites tumour cells in an in vivo test after i.p. application in mice.
It is an object of the present invention to provide novel pharmaceutical preparations with tumour-inhibiting effect for the prophylaxis and treatment of tumours, in particular malignant tumours, such as carcinomas in humans and in larger mammals.
It has now been surprisingly found that the valepotriates defined above have a tumourinhibiting effect in humans and larger mammals in doses which amount to a multiple of the doses used clinically hitherto, namely in daily doses of at least 700 mg.
Accordingly, one aspect of the present invention provides a pharmaceutical preparation for the treatment of tumours in humans and mammals, wherein the preparation is in the form of an individual dosage unit containing at least 100 mg of one or more valepotriates.
According to another aspect of the present invention there is provided a pharmaceutical preparation for the treatment of tumours in humans and mammals, wherein the preparation is presented in the form of daily doses, each comprising sufficient of the aforesaid dosage units as to provide at least 700 mg of said valepotriate(s).
The invention also resides in an individual dosage unit containing at least 100 mg of one or more valepotriates for use in the treatment of tumours in humans and mammals.
The valepotriates may be used as tumourinhibiting substances either individually or as mixtures, e.g. as valepotriate mixtures, which are obtained from extracts of roots and rhizomes of various types of valerianaceae and centranthus.
The most important representatives of the valepotriates are didrovaltratum, valtratum, isovaltratum and acevaltratum. Further examples are 7-homovaltratum, homoacevaltratum, 1homovaltratum, 11 -a-aceisovaltratum, 1-a- acevaltratum, acetoxyhydroxydidrova Itratum, isovaleroxyhydroxydidrovaltratum, isodidrovaltratum and homodidrovaltratum. For example, genuine mixtures of valepotriates may be used as valepotriate mixtures, which contain the valepotriates in their natural ratio of components, as occurs in the following types of valerianaceae and centranthus which are used pharmaceutically: Valeriana officinalis L.,
Valeriana wallichiiD.C., Valeriana ja tamansll Jones, Valeriana edulis procera Mey, Centranthus umber D.C.
If desired, genuine valepotriate mixtures from mixtures of different types of valerianaceae or centranthus may be used. Valepotriates with a monoene structure are preferred i.e. compounds of the Formula I, in which A and B each signify hydrogen, in particular didrovaltratum and homodidrovaltratum, or valepotriate mixtures which contain a proportion of at least 50%, e.g.
5095% monoenic compounds, principally didrovaltratum. For example, suitable mixtures include those which contain 70 to 90% monoenic compounds, in particular didrovaltratum and/or homodidrovaltratum and 10 to 30% dienic compounds, in particular valtratum and/or isovaltratum, for examples mixtures containing 70 to 90% didrovaitratum and homodidrovaltratum, 10 to 25% isovaltratum and/or vaitratum and 1 to 7% acevaltratum. Also mixtures of valepotriates comprising 65 to 85% by weight of didrovaltratum, 10 to 25% by weight of isovaltratum and 2 to 7% by weight of acevaltratum may be used. Preferably, the genuine valepotriate mixture obtained from
Valeriana wallichiiD.C. is used.
The valepotriates, because of their specific tumour-inhibiting effect and their good tolerability can be administered over a period of several weeks at daily doses of at least 700 mg for the prophylaxis and treatment of tumours, in particular malignant tumours, such as carcinomas, e.g. carcinoma of the liver, carcinoma of the colon, carcinoma of the stomach, carcinoma of the breast, carcinoma of the lung, carcinoma of the kidney, carcinoma of the uterus or carcinoma of the prostate and also sarcomas and haemoblastoses.
The dosage may vary in accordance with the nature of the condition which is to be treated and the valepotriate which is used. Good prophylatic and curative effects can be obtained in humans and larger mammals generally with treatments over several weeks, with preferably orally administered daily doses of valepotriates of at least 700 mg for example 700 to 2100 mg (corresponding to a mg/kg dose per os of 10 to 30), in particular daily doses of 800 to 1 500 mg.
These daily doses are expediently administered in several part doses, e.g. in 2 to 6 part doses distributed over the day, each part dose thus comprising an individual dosage unit containing more than 100 mg of the valepotriates.
In clinical investigations on cancer patients, prolonged administration of daily doses of at least 700 mg of the valepotriates shows cancerostatic and redifferentiating effects with regard to a number of cancerous diseases. In these investigations, the valepotriates exhibit high specificity in their anti-tumour effect and an extremely low toxicity and good tolerability. None of the chemotherapeutic cancerostatic preparations found in clinical use today, and which, as is known, are also general cytostatic preparations, has a high specificity of anti-tumour effect such as the valepotriates. The known intense side-effects from chemotherapeutic cancerostatic preparations in use clinically to date do not occur in treatment with valepotriates.The only side-effects which are observed are a lack of appetite caused by a loss of sodium and chlorine ions, which can be completely overcome by additional doses of common salt, and a reduction of the intestinal motility with a tendency to constipation, which likewise can be treated symptomatically without difficulty.
The treatment with valepotriates is favourably compatible with dietetic and/or medicative provisions of care which have been usual to date in the care of cancer, so that if desired these may be retained during the treatment.
Thus it could be established in clinical
investigations on 26 patients, who were suffering
from various types of cancer, to some extent at
greatly advanced stages, that treatment over
several weeks by administration of oral daily
doses of 800 to 1 500 mg of a genuine
valepotriate mixture obtained from Valeriana wallichllD.C., containing 83.5% of a
didrova Itratu m/homodidrovaltratum mixture, 14.8% of a valtratum/isovaltratum mixture and
1.7% acevaltratum, a substantial improvement
took place in their general condition (decrease in
pain resulting from tumour activity, movement of
the tumour-specific pathological biochemical
enzyme values towards normalisation) and a
decrease in the metastases and regression of the
tumour took place.Where the patients were
under dietetic and/or medicative protective care
which is usual in the treatment of cancer, this was
retained during treatment. Amongst the patients
treated were patients with excessive liver
metastasis after previously operated carcinomas
of the colon, patients with metastasing carcinoma
of the kidney, patients with carcinomas of the
breast, patients with recidivating metastasis of a
previously operated synovialoma, one of the most
difficult tumours to treat, patients with carcinoma
of the lung and patients with carcinoma of the
pigment.
Several in-patients at a greatly advanced stage
of disease had already improved after 4 to 5 weeks' treatment to such a large extent that they
could be released from the hospital free of discomfort.
Improvements of this type could not be effected in the case of the above-mentioned conditions of disease, either using a hitherto conventional chemotherapy or using another hitherto estabiished cancer therapy.
Owing to the high specificity of their antitumour effect and their good tolerability, the valepotriates, in contrast to the classic chemotherapy, are well suited to a long-term administration. In view of the absence of systemic toxicity, treatment with valepotriates, unalike the toxic chemotherapy, may be used relatively early on as protective therapy over a long period.
Preferably, the valepotriates are administered orally.
In the present pharmaceutical preparations the valepotriates may be compounded together with conventional pharmaceutical adjuvant and/or carrier substances. Tablets, in particular tablets covered with a film, capsules, pellets, granulates and dragees are examples of preparations which can be administered orally. The vaiepotriate content per individual dose of these preparations is substantially higher than the valepotriate content of hitherto known preparations containing valerian extract and/or valepotriates.
Thus the present preparation has per individual dosage unit a valepotriate content of at least 100 mg, preferably 100 to 800 mg, more preferably 1 50 to 500 mg per individual dose. Preferably, the valepotriates are contained in the preparations in microencapsulated form to improve stability. The micro-encapsulation of valepotriates may take place in a manner known per se, e.g. in accordance with the methods described in the DE-OS 28 49 029.
The preparations may contain pharmaceutically conventional solid, inorganic and/or organic carrier substances, such as for example talcum, lactose or starch, or liquid organic carrier substances such as oils, e.g.
triglyceride mixtures of saturated vegetable fatty acids. In addition, they may contain conventional pharmaceutical adjuvants, such as for example lubricants such as magnesium stearate, tablet exploding agents, suspension agents, preservatives, stabilizing agents, taste correctors and suchlike. If desired, they may also contain substances which delay the release of the effective substances, such as for example polyvinylacetates, acrylate- or methacrylatecopolymers, higher fatty alcohols and other waxlike substances.
The valepotriates, which are preferably microencapsulated, may be mixed and formulated with the pharmaceutical adjuvant and/or carrier substances in a manner known per se. For the manufacture of solid forms of medicament, the micro-encapsulated active substances may be mixed for example with the adjuvant and/or carrier substances in the usual manner and granulated. Depending upon the type of active substances used, a directly tabletable powder can, in appropriate instances, be obtained by simple mixing. The granulate or powder may be filled directly into capsules or compressed into tablet cores in the usual manner. These may be formed into dragees in known manner or covered with a film. The valepotriates, suspended in a liquid carrier substance, may also be filled into soft gelatine capsules.
Expediently the preparations may be provided, in a manner known per se, with a film coating which is resistant to gastric juices and is soluble in the intestine. Anionic methacrylic acid/methacrylate ester polymers (e.g. those sold commercially as "Eudragit" L and S ("Eudragit" is a Trade Mark) or cellulose ester- and -ether derivatives, such as cellulose acetate phthalates or hydroxypropylmethyl cellulose phthalates are examples of conventional pharmaceutical polymeric coating materials, which only dissolve at a pH of from 5.5 and therefore protect the preparations from the action of gastric juices and prevent irritation of the gastric mucous membrane.
It may also prove to be favourable to combine the administration of valepotriates in the high doses according to the invention with an additional administration of sodium chloride. The doses of sodium chloride to be used may vary according to the nature of the condition which is to be treated, the type of valepotriates administered and according to the duration of treatment. Daily doses of 1.5 m to 4 g sodium chloride have proved to be suitable. The ratio of chloride doses to valepotriate doses may be for example from 1:1 to 1:5. The sodium chloride may be introduced parenterally or orally, e.g.
administered in the form of a conventional infusion solution, or taken orally for example in the common salt tablets.
The invention also relates to a receptacle which contains the pharmaceutical valepotriate preparations described above and also instructions on taking these valepotriate preparations for the prophylaxis or treatment of tumour diseases. The receptacle may comprise a plurality of compartments each containing a daily dose of at least 700 mg of said valepotriate(s), preferably 700 mg to 2100 mg.
The invention will now be illustrated by the following non-limiting Examples.
EXAMPLE 1
Film-Coated Tablets
A. Tablet Cores
Parts by
weight
Composition:
Microencapsulated valepotriate
mixture * 800
Lactose 66
Cross-linked
polyvinylpyrrolidinone ** 66
Magnesium stearate 8
Total 940 * A powder containing 20% by weight
valepotriates, produced in a manner known per
se according to the method described in the
DOS 28 49 029 through microencapsulation of 1 60 parts by weight of a valepotriate mixture
obtained by extraction from Valeriana wallichii D.C., containing 83.5+4% by weight
didrovaltratu m/homodidrovaltratum-mixture
(containing 10 to 15% homodidrovaltratum), 14.8+1.5 by weight isovaltratum/valtratum
mixture and 1.7+0.5% by weight acevaltratum
with 215 parts by weight gum arabic and 425
parts by weight "Kollidon" VA 64
(Polyvinylpyrrolidone Manufacturer BASF:
"Kollidon" is a Trade Mark).
**=Crospovidone USP 20/NF 1 5 3. Supplement
cross-linked homopolymeric vinylpyrro[idinone, (Commercial product
"Polyplastone" XL Manufacturer GAF;
"Polyplastone" is a Trade Mark).
Manufacture:
The pulverulent microencapsulated valepotriate mixture is mixed with the lactose and the mixture is compacted on a tabletting machine.
The compressed materials obtained are then
passed through a screen with 2 mm screen
aperture. The granulate obtained is mixed with the polyvinylpyrrolidinone and the magnesium stearate, and the mixture is compressed into tablet cores of 940 mg in weight. Each of the cores obtained in this way contains 1 60 mg valepotriates.
B. Film-coated Tablets
The tablet cores are further processed according to Variant B I to form film-coated tablets which are soluble in the stomach, or according to Variant B II to form film-coated tablets which are resistant to gastric juices and are soluble in the small intestine.
Variant B I
Parts by
weight
Composition:
Tablet cores 940
Shellac 6
Hydroxypropylmethylcellulose 86
2910
Polyethylene glycol 4000 27
Propylene glycol 6.5
Titanium dioxide 7.5
Talcum 13.5
Calcium carbonate 13.5
Total 1100
Manufacture:
The tablet cores are uniformly moistened in a coating tank with a 20% solution of shellac in isopropanol and are subsequently dried with hot air at 400 C. This process is repeated until the entire quantity of shellac has been applied.
The hydroxypropylmethylcellulose 2910 is dissolved in water or in a suitable organic solvent, e.g. isopropanol. The remaining adjuvants are worked into the mixture with stirring and homogenizing and the resulting film coating suspension is sprayed in a coating tank onto the cores encased with shellac, and is dried.
Variant B II
Parts by
by weight
Composition:
Tablet cores 940
Shellac 6
"Eudragit" L 1 OOIIY 41.7
Dibutylphthalate 11.5
Polyethylene glycol 6000 3.5
Coloured lac 2.8
Titanium dioxide 8.5
Magnesium stearate 6.9
Talcum 29.1
Total 1050 ***=Anionic polymer of methacrylic acid and
methacrylate acid esters, soluble at from pH
6, Manufacturer: Rohm GmbH.
Manufacture:
The tablet cores are encased with shellac, as described in Variant B I. "Eudragit" L 100 is dissolved in a suitable organic solvent, e.g.
isopropanol, the remaining adjuvants are worked into the solution with stirring and homogenizing and the resulting film coating suspension is sprayed onto the cores, which have been encased with shellac, in a coating tank and dried.
EXAMPLE 2
Capsules
Parts by
weight
Composition:
Microencapsulated 518.5
valepotriate mixture
Magnesium stearate 6.5
Total 525
Manufacture:
The pulverulent microencapsulated valepotriate mixture, which is the same as that used in Example 1, is compacted in a tabletting machine. Subsequently the compressed material is passed through a screen with 1.6 mm screen aperture. The granulate thus obtained is mixed with the magnesium stearate and the mixture is filled into hard gelatine capsules of size 00. Each capsule contains 525 mg powder mixture corresponding to 100 mg valepotriates.
EXAMPLE 3
Sachets
Parts by
weight
Composition:
Microencapsulated 3200
valepotriate mixture
Highly dispersed silicic 1 6 acid ("Aerosil")
Total 3216
Manufacture:
The pulverulent microencapsulated valepotriate mixture, which is the same as that used in Example 1, is mixed with the "Aerosil" and the mixture is filled into sachets in portions of 3.216 g. Each sachet contains 640 mg valepotriates. In order to manufacture sachets with a content of 800 mg valepotriates, the sachets are filled with portions of 4.020 g mixture per sachet.
EXAMPLE 4
Soft Gelatine Capsules
A) Capsules with a valepotriate content of 1 60 mg.
Parts by
weight
Composition:
Valepotriate mixture (mixture 1 60 obtained from Valeriana
wallichii D.C., of the composition
defined in Example 1) "Miglyol" 812**** 148
Total 308 ****=oily triglyceride mixture of saturated
vegetable fatty acids with C8-, Cl 0- and
C12-chain length, Manufacturer: Dynamit
Nobel AG.
Manufacture:
The valepotriate mixture is dissolved in the "Miglyol" 812 with slight heating and stirring.
The solution is filled into soft gelatine capsules containing an average 302 microlitres solution, with a valepotriate content per capsule of 1 60 mg.
B) Capsules with a valepotriate content of 240 mg.
Parts by
weight
Composition:
Valepotriate mixture 240 "Miglyol" 812 222
Total 462
The valepotriate mixture is dissolved in the "Miglyol" 812 with slight heating and stirring and the solution is filled into soft gelatine capsules containing an average 462 microlitres solution with a valepotriate content per capsule of 240 mg.
C) Capsules with a valepotriate content of 320 mg.
Parts by
weight
Composition:
Valepotriate mixture 320 "Miglyol" 812 296
Total 616
The valepotriate mixture is dissolved in the "Miglyol" 812 with slight heating and stirring and the solution is filled into soft gelatine capsules containing an average 616 microlitres solution with a valepotriate content per capsule of 320 mg.
D) Capsules with a valepotriate content of 500 mg.
Parts by
weight
Composition:
Valepotriate mixture 500 "Miglyol" 812 424
Total 924
The valepotriate mixture is dissolved in the "Miglyol" 812 with slight heating and stirring.
The solution is filled into soft gelatine capsules containing on average 924 microlitres solution with a valepotriate content per capsule of 500 mg.
Claims (26)
1. A pharmaceutical preparation for the treatment of tumours in humans and mammals, wherein the preparation is in the form of an individual dosage unit containing at least 100 mg of one or more valepotriates.
2. A preparation as claimed in claim 1, wherein the dosage unit contains from 100 mg to 800 mg of said valepotriate(s).
3. A preparation as claimed in claim 1 or 2, wherein the dosage unit contains from 1 50 mg to 500 mg of said valepotriate(s).
4. A preparation as claimed in any one of claims 1 to 3, wherein the preparation comprises one or more valepotriates with a monoene structure.
5. A preparation as claimed in claim 4, wherein the valepotriate with a monoene structure is didrovaltratum.
6. A preparation as claimed in claim 4 or 5, wherein the valepotriates comprise at least 50% by weight of monoenic valepotriate(s).
7. A preparation as claimed in any one of claims 1 to 6, wherein the preparation comprises a mixture of valepotriates comprising from 70 to 90% by weight of didrovaltratum and from 10 to 30% by weight of dienic valepotriate(s).
8. A preparation as claimed in claim 7, wherein the dienic valepotriate(s) comprise(s) isovaltratum and/or valtratum.
9. A preparation as claimed in any one of claims 1 to 6, wherein the preparation comprises a mixture of valepotriates comprising from 65 to 85% by weight of didrovaltratum, from 10 to 25% by weight of isovaltratum and/or valtratum and from 2 to 7% by weight of acevaltratum.
10. A preparation as claimed in any one of claims 1 to 9, wherein the valepotriates are present as a mixture of didrovaltratum and dienic valepotriates in a quantitative proportion corresponding to the natural valepotriate composition in Valeriana wallichiiD.C.
11. A preparation as claimed in any one of claims 1 to 10, wherein the dosage unit is prepared in a form for oral administration.
12. A preparation as claimed in any one of claims 1 to 11, wherein the dosage unit is a tablet.
13. A preparation as claimed in any one of claims 1 to 11, wherein the dosage unit is a capsule.
14. A preparation as claimed in any one of claims 1 to 11, wherein the dosage unit is a sachet.
1 5. A preparation as claimed in any one of claims 11 to 13, wherein the dosage unit has a coating resistant to gastric juices.
1 6 A pharmaceutical preparation for the treatment of tumours in humans and mammals, wherein the preparation is presented in the form of daily doses, each comprising sufficient of the individual dosage units claimed in any preceding claim as to provide at least 700 mg of said valepotriate(s).
17. A preparation as claimed in claim 16, wherein each daily dose is from 700 mg to 2100 mg of said valepotriate(s).
18. A preparation as claimed in claim 1 6 or 17, wherein each daily dose is from 800 mg to 1 500 mg of said valepotriate(s).
1 9. A preparation as claimed in any one of claims 16 to 18, wherein each daily dose is additionally presented together with from 1.5 g to 4.0 g of sodium chloride.
20. A preparation as claimed in claim 19, wherein the ratio of valepotriates to sodium chloride is from 1:1 to 1:5.
21. A pharmaceutical preparation for the treatment of tumours in humans and mammals substantially as hereinbefore described in any one of the foregoing Examples.
22. A receptacle containing a pharmaceutical preparation as claimed in any preceding claim and instructions for taking the preparation for the treatment of tumours.
23. A receptacle as claimed in claim 22, wherein the receptacle comprises a plurality of compartments each containing a daily dose of at least 700 mg of said valepotriate(s).
24. A receptacle as claimed in claim 22 or 23, wherein the receptacle additionally comprises for each daily dose of valepotriate(s) a daily dose of 1.5 g to 4.0 g of sodium chioride.
25. A receptacle as claimed in claim 24, Wherein for each daily dose the ratio of valepotriate(s) to sodium chloride is from 1:1 to 1:5.
26. An individual dosage unit containing at least 100 mg of one or more valepotriates for use in the treatment of tumours in humans and mammals.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE3322337A DE3322337A1 (en) | 1983-06-22 | 1983-06-22 | NEW PHARMACEUTICAL PREPARATIONS WITH ANTITUARY EFFECT |
Publications (2)
Publication Number | Publication Date |
---|---|
GB8415453D0 GB8415453D0 (en) | 1984-07-25 |
GB2141930A true GB2141930A (en) | 1985-01-09 |
Family
ID=6202002
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB08415453A Withdrawn GB2141930A (en) | 1983-06-22 | 1984-06-18 | Novel pharmaceutical preparations with anti-tumour effect |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0129822A3 (en) |
JP (1) | JPS6013713A (en) |
BE (1) | BE899987A (en) |
DE (1) | DE3322337A1 (en) |
GB (1) | GB2141930A (en) |
IT (1) | IT1196147B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105541780A (en) * | 2016-03-02 | 2016-05-04 | 杭州市第一人民医院 | Valerenic acid derivatives, pharmaceutical composition comprising same and anti-tumor application of valerenic acid derivatives |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS58188774U (en) * | 1982-06-10 | 1983-12-15 | ジューキ株式会社 | Control device for automatic sewing equipment |
JPH0194893A (en) * | 1987-09-24 | 1989-04-13 | Frankl & Kirchner Gmbh & Co Kg Fab Elektromot | Industrial sewing machine |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2849029A1 (en) * | 1978-11-11 | 1980-05-22 | Kali Chemie Pharma Gmbh | STABLE VALEPOTRIATE PREPARATIONS AND METHOD FOR THE PRODUCTION THEREOF |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2011235A1 (en) * | 1970-03-10 | 1971-10-14 | Sons geb Heimbach, Ruth, 4050 Mönchengladbach, Heimbach, Irmgard, 4060 Viersen | Anti-inflammatory compns with penetratingproperties |
-
1983
- 1983-06-22 DE DE3322337A patent/DE3322337A1/en not_active Withdrawn
-
1984
- 1984-06-15 IT IT21431/84A patent/IT1196147B/en active
- 1984-06-18 GB GB08415453A patent/GB2141930A/en not_active Withdrawn
- 1984-06-18 EP EP84106976A patent/EP0129822A3/en not_active Withdrawn
- 1984-06-19 JP JP59124623A patent/JPS6013713A/en active Pending
- 1984-06-21 BE BE0/213197A patent/BE899987A/en not_active IP Right Cessation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2849029A1 (en) * | 1978-11-11 | 1980-05-22 | Kali Chemie Pharma Gmbh | STABLE VALEPOTRIATE PREPARATIONS AND METHOD FOR THE PRODUCTION THEREOF |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105541780A (en) * | 2016-03-02 | 2016-05-04 | 杭州市第一人民医院 | Valerenic acid derivatives, pharmaceutical composition comprising same and anti-tumor application of valerenic acid derivatives |
Also Published As
Publication number | Publication date |
---|---|
GB8415453D0 (en) | 1984-07-25 |
JPS6013713A (en) | 1985-01-24 |
IT1196147B (en) | 1988-11-10 |
IT8421431A0 (en) | 1984-06-15 |
EP0129822A2 (en) | 1985-01-02 |
BE899987A (en) | 1984-10-15 |
IT8421431A1 (en) | 1985-12-15 |
DE3322337A1 (en) | 1986-05-15 |
EP0129822A3 (en) | 1985-09-11 |
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