GB1573730A - Pharmaceutical compositions - Google Patents
Pharmaceutical compositions Download PDFInfo
- Publication number
- GB1573730A GB1573730A GB23763/78A GB2376378A GB1573730A GB 1573730 A GB1573730 A GB 1573730A GB 23763/78 A GB23763/78 A GB 23763/78A GB 2376378 A GB2376378 A GB 2376378A GB 1573730 A GB1573730 A GB 1573730A
- Authority
- GB
- United Kingdom
- Prior art keywords
- cyanoaziridine
- composition according
- pharmaceutical compositions
- carrier
- agent
- 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.)
- Expired
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- PGZUFTROELAOMP-UHFFFAOYSA-N aziridine-2-carbonitrile Chemical compound N#CC1CN1 PGZUFTROELAOMP-UHFFFAOYSA-N 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 8
- 230000004962 physiological condition Effects 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 239000000872 buffer Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000011248 coating agent Substances 0.000 claims description 2
- 238000000576 coating method Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 2
- 210000000813 small intestine Anatomy 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 239000000796 flavoring agent Substances 0.000 claims 1
- 235000013355 food flavoring agent Nutrition 0.000 claims 1
- 235000003599 food sweetener Nutrition 0.000 claims 1
- 239000003765 sweetening agent Substances 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 210000000265 leukocyte Anatomy 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 239000000463 material Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000001828 Gelatine Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000003327 cancerostatic effect Effects 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 229920006158 high molecular weight polymer Polymers 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- YLGXILFCIXHCMC-JHGZEJCSSA-N methyl cellulose Chemical compound COC1C(OC)C(OC)C(COC)O[C@H]1O[C@H]1C(OC)C(OC)C(OC)OC1COC YLGXILFCIXHCMC-JHGZEJCSSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- -1 stearic acid) Chemical class 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QVDCANBBJMFTOO-UHFFFAOYSA-N aziridine-1-carbonitrile Chemical compound N#CN1CC1 QVDCANBBJMFTOO-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 125000005624 silicic acid group Chemical class 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000001790 virustatic effect Effects 0.000 description 1
- 239000003643 water by type Substances 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
(54) PHARMACEUTICAL COMPOSITIONS
(71) We, BOEHRINGER MANNHEIM GmbH., of Mannheim-Waldhof, Federal
Republic of Germany, a Body Corporate organised under the laws of the 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 is concerned with new pharmaceutical compositions.
2-Cyanoaziridine is a chemical intermediate which has been known for some time (cf.
Ang. Chem., 84, 108-109/1972). Various derivatives of this compound and the pharmacological properties thereof have been described. However, we have found that this compound itself, when administered orally to rats, brings about a marked increase in the number of leukocytes and lymphocytes, whereas the number of erythrocytes remains substantially unchanged. Furthermore, a considerable increase in the anti-body forming spleen cells has been observed after the administration of 2-cyanoaziridine. These experiments show that, by the administration of 2-cyanoaziridine, the immune defence of animals is strongly stimulated so that this compound can be used therapeutically not only in cases of bacterial and viral infection but also as a cancerostatic.
Furthermore, we have ascertained that numerous derivatives, such as are described, for example, in German Patent Specifications Nos.2,528,460; 2,644,820; 2,656,240 and 2,656,323, break down under physiological conditions with the liberation of 2cyanoaziridine. Insofar as this decomposition takes place quickly, it is to be assumed that at least a part of the effect of these products is due to the action of 2-cyanoaziridine although, of course, a direct action of this compound is not excluded.
Thus according to the present invention, there are provided pharmaceutical compositions which contain 2-cyanoaziridine and/or at least one derivative thereof which, under physiological conditions, liberates 2-cyanoaziridine, together with a solid or liquid pharmaceutical diluent or carrier.
In addition to 2-cyanoaziridine and/or at least one derivative thereof which, under physiological conditions, liberates 2-cyanoaziridine, the new compositions according to the present invention can also contain at least one other known therapeutic substance with bacteriostatic virostatic and/or cancerostatic properties, the action of which is strengthened or supplemented by the immune-stimulating action of the active compound or compounds used according to the present invention.
For the preparation of the pharmaceutical compositions according to the present invention, 2-cyanoaziridine and/or at least one derivative thereof which, under physiological conditions, liberates 2-cyanoaziridine, is mixed in the usual way with appropriate carrier substances and formed, for example, into dosage units, such as tablets or dragees, or, with the addition of appropriate adjuvants, suspended or dissolved in water or in an oil, such as olive oil, and placed into hard gelatine capsules. Since the active material is somewhat acid labile, the composition can, if necessary, be provided with a coating which only dissolves in the alkaline medium of the small intestines or it can be mixed with an appropriate carrier material, for example a high molecular weight fatty acid or carboxymethylcellulose. Solid carrier materials which can be used include, for example, starch, lactose, mannitol, methyl cellulose, talc, highly dispersed silicic acids, high molecular weight fatty acid (such as stearic acid), gelatine, agar-agar, calcium phosphate, magnesium stearate, animal and vegetable fats and solid high molecular weight polymers (such as polyethylene glycol). Compositions which are suitable for oral administration can, if desired, contain flavouring and/or sweetening materials.
As injection medium, which must be sterile, it is preferable to use water which contains the conventional additives for injection solutions, such as stabilising agents, solubilising agents or weakly alkaline buffers. Additives of this kind include, for example, phosphate and carbonate buffers, ethanol, complex-forming agents (such as ethylenediaminetetraacetic acid and the non-toxic salts thereof) and high molecular weight polymers (such as polyethylene oxide) for viscosity regulation.
EXPERIMENTAL RESULTS. a) Rate of hydrolysis of 2-cyanoaziridine derivatives.
In order to ascertain to what extent derivatives of 2-cyanoaziridine are able to liberate 2-cyanoaziridine in solution at physiological pH values, there was determined the rate of hydrolysis at a pH value of 2, which corresponds to a 0.01N hydrochloric acid and which can also be present in the stomach.
High pressure liquid chromatography (HPLC) proved to be the most suitable method of analysis. For this purpose about 1% by weight of the compound to be investigated was dissolved in 0.01N hydrochloric acid and maintained for 16 hours in a thermostatically controlled water-bath at 25"C. Samples of about 100 1ll. were taken from the solutions and then analysed by HPLC.
Separation was carried out in a 0.25 metre long column, the inner diameter of which was 4.6 mm. The column material used was Nucleosil 10-C-18, with a particle size of 10 + 1.5 clam. The mobile phase used was degassed, distilled water with a rate of flow of 1.0 ml./minute at a pressure of about 40 bar and a column temperature of 25"C. The detector used was a Waters differential refractometer 401.
For the determination of the substance-specific factor of 2-cyanoaziridine against n-propanol, 11.66 mg. 2-cyanoaziridine and 92.33 mg. n-propanol were dissolved in 10.0 ml. 0.01 hydrochloric acid. 100 'ill. amounts of this solution were chromatographed under the above-described conditions and, from 5 analyses, there was calculated the average value of the material-specific factor of 2-cyanoaziridine against n-propanol. After introduction of this average value into a calculator, the individual hydrolysis samples were analysed. In the case of 1-carboxamido-2-cyanoaziridine and 1-N-formylglycyl-2-cyanoaziridine, there was also determined, in an analogous manner, a substance-specific factor for the starting materials in order thus to be able to determine the amount of starting material still present.
The results obtained are summarised in the following Table.
Titrimetric examination of the hydrolysis of l-carboxamido-2-cyanoaziridine.
11.35 mg. 1-Carboxamido-2-cyanoaziridine were dissolved in 10.0 ml. 0.01N hydrochloric acid and the solution thermostatically controlled at 25"C. The solution had a pH value of 2.05. This pH value was kept constant with the help of a Radiometer-titration automatic device as pH stat. In the case of complete hydrolysis, a consumption of 1.02 ml. 0.01N hydrochloric acid would have been necessary in order to neutralise the resultant ammonia.
After 15 hours, the pH value was still constant at 2.05. A consumption of 0.01N hydrochloric acid was not noted. b) Determination of leukocytes after a single oral administration to rats
In order to ascertain the immune-stimulation action of 2-cyanoaziridine and of its derivatives, the stimulation of the leukocyte formation was investigated in rats. Use was made of female adult Sprague-Dawley rats obtained from the firm WIGA (Gassner,
Sulzfeld), which had a body weight of 180 - 220 g. The animals were maintained at a constant temperature (23 i 1"C.) and at a constant atmospheric humidity (55 + 5%) in a 12 hour day/night rhythm. The animals were given rat pellets available under the name "Sniff" from the firm Intermast, Soest and water was available ad libitum. Groups of 10 rats received once only the substance to be investigated (220 mg. thereof dissolved in 10 ml.
0.5% tylose solution/kg. body weight), which was administered with the help of a stomach probe. For control purposes, groups of 10 animals were merely treated with 10 ml. of a 5% tylose solution/kg. body weight. Before the administration, the animals were fasted and blood was collected from the retroorbital vein complex with the help of a he arinised injection capillary needle (type B 3095/2 of the firm Sherwood Med. Inc., St. Louis and the leukocytes determined in known manner with the use of a Coulter counter.
On the fourth day, blood was again collected from the animals from the retroorbital vein complex and the leukocytes counted. From the individual values there were determined the average values with standard deviations. The experimental groups were only evaluated when the control groups showed no physiological variations.
The following Table also shows the leukocyte counts before administration and on the fourth day, as well as the quotients. These data show that, of the substances investigated by oral administration, those bring about a significant increase of the leukocyte count and thus are strongly immune-stimulating which, under physiological conditions, split off 2cyanoaziridine to a significant extent.
TABLE
Initial resultant amount of Leukocyte count in Leukocyte amount amount of starting thousands quotient of 2-cyano- material compound aziridine still 0 day 4 day 4/0 (mg) in % of present theory in % 2-[2-Cyanoaziridinyl-(1)]- 107.3 100 # 8.0 13.6 1.7 2-[2carbamoyl-aziridinyl] (1)]-propane 1-N-Formylgycyl-2-cyano- 105.3 54.9+ 7.9 8.5 16.4 1.9 aziridine 1-(N-Methylcarbamoyl)-2- 96.1 # ca. 100 8.3 8.6 1.02 cyanoaziridine 1-(N-p-Sulphamoylphenyl- 102.5 1.5 86.1++ 10.9 11.2 1.02 carbamoyl)-2-cyanoaziridine 1-Carboxamido-2-cyano 104.8 # 90.46+++ 8.9 9.5 1.07 aziridine 2-Cyanoaziridine 103.4 100 ./. 7.6 18.1 2.4 + a part of the initially formed 2-cyanoaziridine has entered into secondary reactions with other hydrolysis products.
++ starting material was not comPletely dissolved in 0.01N HC1 and was measured in potassium phosphate buffer (H2.
+++ since the separation of 2-cyanoaziridine and 1-carboxamido-2-cyanoaziridine is not very good, a titrimetric process was additionally employed.
Claims (7)
1. Pharmaceutical compositions, comprising 2-cyanoaziridine and/or at least one derivative thereof which, under physiological conditions, liberates 2-cyanoaziridine, together with a solid or liquid pharmaceutical diluent or carrier.
2. Composition according to claim 1, wherein the liquid diluent or carrier is sterile.
3. Composition according to claim 1 or 2, wherein the liquid diluent or carrier contains a stabilising agent and/or a solubilising agent and/or a buffer.
4. Composition according to claim 1 or 3, wherein a flavouring agent and/or sweetening agent is present.
5. Composition according to any of the preceding claims, whenever in the form of a dosage unit.
6. Composition according to claim 6, wherein the dosage unit is provided with a coating which only dissolves in the alkaline medium of the small intestines.
7. Pharmaceutical compositions according to claim 1, substantially as hereinbefore described.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772736296 DE2736296A1 (en) | 1977-08-12 | 1977-08-12 | USE OF 2-CYAN-AZIRIDINE AND ITS DERIVATIVES FOR IMMUNESTIMULATION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1573730A true GB1573730A (en) | 1980-08-28 |
Family
ID=6016187
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB23763/78A Expired GB1573730A (en) | 1977-08-12 | 1978-05-30 | Pharmaceutical compositions |
Country Status (8)
| Country | Link |
|---|---|
| AU (1) | AU3888678A (en) |
| BE (1) | BE869686A (en) |
| DE (1) | DE2736296A1 (en) |
| FI (1) | FI782419A7 (en) |
| FR (1) | FR2399840A1 (en) |
| GB (1) | GB1573730A (en) |
| NL (1) | NL7808275A (en) |
| SE (1) | SE7808520L (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5369119A (en) * | 1988-07-28 | 1994-11-29 | Boehringer Mannheim Gmbh | Use of imexon as an immune suppressive and pharmaceutical compositions containing imexon |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3825667A1 (en) * | 1988-07-28 | 1990-03-15 | Boehringer Mannheim Gmbh | USE OF IMEXON AS IMMUNOSUPPRESSIVE |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2528460A1 (en) * | 1975-06-26 | 1977-01-13 | Boehringer Mannheim Gmbh | 1-Carbamoyl 2-cyano aziridine as immunostimulant - for therapy of bacterial and viral infections |
| DE2644820A1 (en) * | 1976-10-05 | 1978-04-06 | Boehringer Mannheim Gmbh | (N)-Acyl-2-cyano-aziridine-1-carboxamide and 1-thiocarboxamide derivs. - with carcinostatic and immunostimulant activity |
| DE2656323A1 (en) * | 1976-12-11 | 1978-06-15 | Boehringer Mannheim Gmbh | Immunostimulant aziridine carboxylic acid derivs. - with substits. in 2-position |
-
1977
- 1977-08-12 DE DE19772736296 patent/DE2736296A1/en not_active Withdrawn
-
1978
- 1978-05-30 GB GB23763/78A patent/GB1573730A/en not_active Expired
- 1978-08-07 FI FI782419A patent/FI782419A7/en not_active Application Discontinuation
- 1978-08-08 NL NL787808275A patent/NL7808275A/en not_active Application Discontinuation
- 1978-08-09 SE SE7808520A patent/SE7808520L/en unknown
- 1978-08-11 BE BE78189840A patent/BE869686A/en unknown
- 1978-08-11 FR FR7823683A patent/FR2399840A1/en not_active Withdrawn
- 1978-08-14 AU AU38886/78A patent/AU3888678A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5369119A (en) * | 1988-07-28 | 1994-11-29 | Boehringer Mannheim Gmbh | Use of imexon as an immune suppressive and pharmaceutical compositions containing imexon |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2399840A1 (en) | 1979-03-09 |
| DE2736296A1 (en) | 1979-02-22 |
| BE869686A (en) | 1979-02-12 |
| AU3888678A (en) | 1980-02-21 |
| NL7808275A (en) | 1979-02-14 |
| SE7808520L (en) | 1979-02-13 |
| FI782419A7 (en) | 1979-02-13 |
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