CN1075255A - The new pharmaceutical composition of gastric cells protective effect is secreted and had to gastric acid inhibitory - Google Patents
The new pharmaceutical composition of gastric cells protective effect is secreted and had to gastric acid inhibitory Download PDFInfo
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- CN1075255A CN1075255A CN 92115369 CN92115369A CN1075255A CN 1075255 A CN1075255 A CN 1075255A CN 92115369 CN92115369 CN 92115369 CN 92115369 A CN92115369 A CN 92115369A CN 1075255 A CN1075255 A CN 1075255A
- Authority
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- Prior art keywords
- chemical compound
- logical formula
- atom
- cimetidine
- hydrogen atom
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
-
- 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
- A61K31/415—1,2-Diazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/24—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical 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)
Abstract
The present invention relates to the gastric acid inhibitory secretion and produce the new Pharmaceutical composition of gastric cells protective effect; said composition comprises chemical compound with the chemical compound of a kind of general formula (II) or a kind of general formula (I) as active component; adding agent with carrier known in the art and tax mixes; further relate to its preparation method and be used for the treatment of and/or prevent the mammal esophagus of (comprising the people), the Therapeutic Method of harmonization of the stomach duodenal inflammation and ulcer.
Description
The present invention relates to gastric acid inhibitory and secrete and have the new pharmaceutical composition of gastric cells protective effect, said composition comprises the chemical compound with a kind of logical formula II,
Wherein on behalf of an oxygen atom or sulphur atom and R, X represent a hydrogen atom, a hydroxyl, C
1-C
4Alkyl or C
1-C
4Alkoxyl,
Or a kind of chemical compound of logical formula III,
R wherein
1Represent a hydrogen atom or halogen atom,
With 10 of a kind of chemical compound of logical formula IV: 1-1: 10(W/W) mixture,
Or a kind of chemical compound of logical formula I,
Wherein A represents the group of a general formula (V) or (VI),
Wherein X, R and R
1Define the same and
B is the protonated form of logical formula IV chemical compound,
Be active component, add agent with known carrier of prior art and tax and mix.
The invention particularly relates to and comprise with 4-oxo-4H-1-.alpha.-5:6-benzopyran-2-carboxylic acid 4-oxo-4H-1-benzo thiapyran-2-carboxylic acid or 3-(4-chlorobenzene sulphonyl)-acrylic acid and cimetidine 10: 1-1: 10(W/W) mixture; Or 4-oxo-4H-1-.alpha.-5:6-benzopyran-2-carboxylic acid cimetidine salt; Or 4-oxo-4H-1-benzo thiapyran-2-carboxylic acid cimetidine salt; Or 3-(4-chlorobenzene sulphonyl) acrylic acid cimetidine salt is as the new pharmaceutical composition of active component.
The present invention further relates to the method that is used to prepare above pharmaceutical composition and logical formula I noval chemical compound, and wherein A and B definition is the same.
General formula (I a) salt is the chemical compound that is selected from logical formula I,
X represent an oxygen atom or sulphur atom and
R represents a hydrogen atom, a hydroxyl, C
1-C
4Alkyl or C
1-C
4Alkoxyl,
Simultaneously similarly, general formula (I b) salt is the chemical compound that is selected from logical formula I,
R
1Represent a hydrogen atom or halogen atom.
Cimetidine-1-cyano group-2-methyl-3-[2-/(5-Methylimidazole .-4-yl) methyl/thio-ethyl] guanidine is a kind of known H
2Receptor blocking agent.Its gastric acid inhibitory secretion but produce the gastric cells protective effect hardly, so it is to select to be used for the treatment of the medicine of gastric ulcer or gastritis but the purpose that is not suitable for prevention.
Reported several cimetidine salt in the document but do not have a kind of derivant proof more effective than its alkali.European patent specification has been described the salt that cimetidine and aspartic acid and glutamic acid form for the 277th, No. 900, has also described the disalt that aspartic acid cimetidine salt and glutamic acid cimetidine and ascorbic acid form.Infer these salt and offset the toxic and side effects of cimetidine.
European patent specification has been reported the simple salt of some cimetidine for the 255th, No. 376, i.e. acetate, sulfate, hydrochlorate, fumarate, maleate (maleinate) etc.These salt and ammonia react can produce the cimetidine polymorph b.
The general formula of the logical formula I chemical compound of the present invention (I a) and the cimetidine salt of (I b) be new, except that inferring anti-stomachial secretion effect, they have significant gastric cells protective effect.So they not only are suitable for treating ulcer but also can be used as the prevention purpose.These two kinds of effects are not only simple adduction but have observed significant synergism.
The form of salt is by logical formula II or (III), wherein R, X and R
1Define the same and cimetidine alkali is made as initial compounds.Cimetidine alkali is by british patent specification the 2nd, 103, and 206 prepare.Stoichiometrical amount of these compositions is reacted in a kind of organic solvent inert or in the mixture of a kind of inert organic solvents and water, and by heating, or as need promote the formation of salt through refluxing.
Preferred organic is the mixture of methanol or ethanol and ethyl acetate.(also can show) behind the salt formation, come purification residue crude product with this solvent evaporation and through the mixture recrystallization of a kind of inert organic solvents or a kind of atent solvent and water by the elimination of heterogeneous system.
Acetonitrile, acetone, methanol and ether are preferred inert organic solvents.
4-oxo-4H-1-.alpha.-5:6-benzopyran-2-carboxylic acid is a kind of commodity in the initiation material of logical formula II chemical compound, and 4-oxo-4H-1-.alpha.-5:6-benzopyran-2-carboxylic acid can prepare by the method for J.Schmutz etc. (Helv.Chim, Acta 34,769,1951) simultaneously.
In the initiation material of logical formula III, the derivant of 3-benzene sulfonyl acrylic acid and replacement thereof prepares for No. 3572/89 by Hungarian patent application.
Preparation the present invention new Pharmaceutical composition, can be by 10: 1-1: the chemical compound of a kind of logical formula II of mixed 10(W/W), wherein R and X definition be the same, or a kind of chemical compound of logical formula III, wherein R
1Define the cimetidine of the same and logical formula IV, and add agent with commonly used known carrier of prior art or tax and mix.
This new pharmaceutical composition also can be by chemical compound that will a kind of logical formula I, and wherein A and B define the samely, add agent with known carrier or tax and mix and prepare.
The active component of the present composition has been made detailed pharmacological testing.
This conjugate and new compositions; (Shay etc.: Gastroenterology 5 in the test of Shay; 43; 1945); but gastric acid inhibitory secretion; and (A.Robert:Gastroenterology 77,761,1979) produce significant gastric cells protective effect to mouse in the test of Robert.
Further research has determined by aspirin and anxiety (K.D.Rainsford:Agents and Actions 5,553,1975), and the inhibition of the inductive gastric ulcer of indomethacin is made.In current research, female RG-Wistar Mus, fasting 24 hours is handled with test compound, and after 30 minutes, oral 20mg indomethacin also calculates ED
50Value.The results are shown in following table.These data obviously prove compositions and the valuable effect of new salt of the present invention.In pharmacology test, they prove obvious gastric acid inhibitory secretion and produce the gastric cells protective effect.The dosage of estimating the people is in the scope of per kilogram of body weight 50-500 milligram active component.
Table 1
Gastric acid secretion acid ethanol mould aspirin+indomethacin lures
The nervous model of cell of the inhibition type gastric ulcer of leading
Chemical compound (Shay protective effect (Rainsford) model
Test (Robert) dosage 50mg/kg
ED
50ED
50ED
50ED
50
Cimetidine 25 170 40% gastric ulcers 5
4-oxo-4H
-1-.alpha.-5:6-benzopyran 95 3 invalid 25mg/kg
-2-carboxylic acid promotes ulcer
8 12 36% ulcer 9 of embodiment 1
Chemical compound suppresses
ED
50: mg/Kg is oral
Table 1 shows that cimetidine and 4-oxo-4H-1-.alpha.-5:6-benzopyran-best feature of 2-carboxylic acid are to carry out combination by embodiment 1 chemical compound.Because 4-oxo-4H-1-.alpha.-5:6-benzopyran-2-carboxylic acid only slightly the gastric cells protective effect of gastric acid inhibitory secretion and cimetidine be quite low; embodiment 1 chemical compound is secreted with similar speed gastric acid inhibitory to cimetidine, and its gastric cells protective effect has the level of 4-oxo-4H-1-.alpha.-5:6-benzopyran-2-carboxylic acid.
Table 2
Gastric acid secretion acid ethanol mould aspirin+indomethacin lures
The nervous model of cell of the inhibition type gastric ulcer of leading
Chemical compound (Shay protective effect (Rainsford) model
Test (Robert) dosage 50mg/kg
ED
50ED
50ED
50ED
50
Cimetidine 25 170 is at 50mg/kg 5
During dosage 40%
Ulcer suppresses
The 4-oxo-at 50mg/kg
There are not 5.4 25mg/kg 64 during-4H-1 dosage
-benzo thiapyran is imitated and is strengthened anxiety
-2-carboxylic acid
Embodiment 2 20 4 is at 50mg/kg
During chemical compound dosage invalid 6
ED
50: mg/Kg is oral
Table 2 shows that the chemical compound of embodiment 2 has similar to 4-oxo-4H-1-benzo thiapyran and is different from the significant gastric cells protective effect of cimetidine.In the inductive ulcer test of indomethacin, the chemical compound of embodiment 2 remains with the antiulcer action of cimetidine, but does not strengthen aspirin+nervous inductive ulcer (being different from 4-oxo-4H-1-benzo thiapyran-2-carboxylic acid).
Table 3
Gastric acid secretion acid ethanol mould aspirin+indomethacin lures
The nervous model of cell of the inhibition type gastric ulcer of leading
Chemical compound (Shay protective effect (Rainsford) model
Test (Robert) dosage 50mg/kg
ED
50ED
50ED
50ED
50
Cimetidine 25 170 is at 50mg/kg 5
During amount 40%
Ulcer suppresses
(4-16 1.4 19 is at 25mg/kg for 3-
The chlorobenzene sulphonyl) ulcer during dosage
-acrylic acid strengthens
Embodiment 38 4.2 22 is at 50mg/kg
Chemical compound dosage the time invalid
ED
50: mg/Kg is oral
The chemical compound that table 3 shows embodiment 3 its gastric acid secretion inhibitory action and its gastric cells protective effect with and the antiulcer action in aspirin+nervous model, measured aspect constitute component (cimetidine and 3-(4-chlorobenzene sulphonyl) acrylic acid than it) the effect that any one single composition was showed all superior.
Table 4
Oral gastric juice is with oral to taking a picture
Chemical compound n dose volume acid content is than acid secretion ED
50
The inhibition % mg/kg of mg/kg ml/100g umole/100g
+
The west miaow is for woods 5 12.5 2.5 ± 0.5 171.9 ± 61.2 25.9 25
3-(4-chlorine
Benzene sulfonyl) 5 10.0 5.8 ± 0.2 345.8 ± 54.5 1.1 16
Acrylic acid
Embodiment 5 10.0 4.1 ± 0.1 368.9 ± 21.3* 34.0 8
3 salt
5.1:4.9
(W/W) mix
Compound ++ 5 10.0 4.4 ± 0.3 266.5 ± 44.0* 50.9-
(embodiment
4)
2:8 is (real
Execute example 5) 5 10.0 5.7 ± 0.3*, 291.5 ± 18.3* 47.8-
8:2 is (real
Execute example 6) 5 10.0 3.9 ± 0.4*, 315.7 ± 62.2* 43.5-
* compare P≤0.05 with the reality contrast
N animal number of elements
+ based on inhibition to gastric acid secretion
++ cimetidine and 3-(4-chlorobenzene sulphonyl) acrylic acid mixture.
Table 4 shows chemical compound and cimetidine and the 3-(4-chlorobenzene sulphonyl of embodiment 3) acrylic acid various mixture, the inhibition of gastric acid secretion is significantly higher than single cimetidine or each acrylic acid derivative.
It approximately is similar producing the speed that suppresses by various mixture.
The following example is illustrative, is not limitation of the scope of the invention.
Embodiment 1
4-oxo-4H-1-.alpha.-5:6-benzopyran-carboxylic acid cimetidine monocalcium salt compound
With 5.7g(0.03mole) 4-oxo-4H-1-.alpha.-5:6-benzopyran-2-carboxylic acid be suspended in the mixture of 60ml methanol and 40ml ethyl acetate, add 7.57g(0.03mole then) the 60ml methanol solution of cimetidine alkali.Initial heterogeneous system becomes solution rapidly, and this solution of evaporation after 2 hours refluxes.Residue is dissolved in the acetonitrile of 10ml and by adding water under heating and carries out recrystallization.It is dry down at 60 ℃ to filter products therefrom.
Output: 10.5g(76%)
Molten point: 105-107 ℃, 114 ℃ of decomposition points
Analysis result: C
20H
22N
6O
4S2H
2O(478.52)
Value of calculation: C%50.20; H%5.47; N%17.56
Measured value: C%50.40; H%5.89; N%17.51
Embodiment 2
4-oxo-4H-1-.alpha.-5:6-benzopyran-2-carboxylic acid cimetidine salt
With 2.52g(0.01mole) the cimetidine alkali dissolution in the mixture of the heat of 200ml water and 30ml methanol, add 2.06g(0.01mole then) the 30ml methanol suspension of 4-oxo-4H-1-benzo thiapyran-2-carboxylic acid.Heat this mixture to the boiling, use activated carbon decolorizing, the filtration and with the filtrate vapourisation under reduced pressure.Residue is through cooling and crystallization adds 30ml acetone and 10ml methanol mixture then, leaches white crystals and washs with ether.
Output: 3.52g(77%)
Molten point: 146-148 ℃ (decomposition point)
Embodiment 3
3-(4-chlorobenzene sulphonyl) acrylic acid cimetidine salt
With 1.23g(5mmole) 3-(4-chlorobenzene sulphonyl) acrylic acid and 1.26g(5mmole) cimetidine alkali is dissolved in the 20ml methanol.Placed 1 hour, then the evaporation and with residue ether crystallization.
Output 2.1g(84%)
Fusing point: 84-90 ℃ (decomposition point)
Embodiment 4
The active component compositions
The 5.1g cimetidine is mixed with 4.9g 4-oxo-4H-1-.alpha.-5:6-benzopyran-2-acrylic acid.
Output: 10g
Embodiment 5
The active component compositions
With 20g cimetidine and 80g 3-(4-chlorobenzene sulphonyl) acrylic acid mixes.
Output: 100g
Embodiment 6
The active component compositions
With 80g cimetidine and 20g 3-(4-chlorobenzene sulphonyl) acrylic acid mixes.
Output: 100g
Embodiment 7
The active component compositions
With 60g cimetidine and 40g 3-(4-chlorobenzene sulphonyl) acrylic acid mixes.
Output: 100g
Embodiment 8
Pharmaceutical composition
The mixture of following component is stirred evenly, make the tablet pre-composition with 15ml water then, and be pressed into tablet.
4-oxo-4H-1-.alpha.-5:6-benzopyran-2-carboxylic acid 5.7g
Cimetidine 7.5g
Magnesium stearate 10g
Polyvinylpyrrolidone 4g
Talcum 6g
Starch 10g
Lactose 20g
Every active component that contains 132mg.
Claims (14)
1, the pharmaceutical composition of gastric acid inhibitory secretion and the protective effect of generation gastric cells comprises the chemical compound with a kind of general formula II,
Wherein X represent an oxygen atom or sulphur atom and
R represents a hydrogen atom, a hydroxyl, or C
1-C
4Alkyl or C
1-C
4Alkoxyl,
Or a kind of chemical compound of logical formula III,
R wherein
1Represent a hydrogen atom or halogen atom,
With 10 of a kind of chemical compound of logical formula IV: 1-1: the mixture of 10 (W/W),
Or a kind of chemical compound of logical formula I,
Wherein A represents the group of a kind of general formula (V) or (VI),
Wherein X, R and R
1Define the same, and
B is the protonated form of logical formula IV chemical compound,
As active component, add agent with known carrier of prior art and tax and mix.
2, according to the Pharmaceutical composition of claim 1, comprise and use a kind of 4-oxo-4H-1-.alpha.-5:6-benzopyran-2-carboxylic acid and cimetidine 10: 1-1: 10(W/W) mixture is as active component.
3, according to the Pharmaceutical composition of claim 1, comprise use with 4-oxo-4H-.alpha.-5:6-benzopyran-2-carboxylic acid cimetidine salt as active component.
4, according to the Pharmaceutical composition of claim 1, comprise and use a kind of 4-oxo-4H-1-benzo thiapyran-2-carboxylic acid and cimetidine 10: 1-1: 10(W/W) mixture is as active component.
5, according to the Pharmaceutical composition of claim 1, comprise use with 4-oxo-4H-1-benzo thiapyran-2-carboxylic acid cimetidine salt as active component.
6,, comprise use with a kind of 3-(4-chlorobenzene sulphonyl according to the pharmaceutical composition of claim 1) acrylic acid and cimetidine 10: 1-1: 10(W/W) mixture is as active component.
7,, comprising use with 3-(4-chlorobenzene sulphonyl according to the pharmaceutical composition of claim 1) acrylic acid cimetidine salt is as active component.
8, the chemical compound of logical formula I, wherein A represents the group of a kind of general formula (V) or (VI) (wherein X represents an oxygen atom or sulphur atom, and R represents a hydrogen atom, a hydroxyl, or C
1-4Alkyl or C
1-4Alkoxyl, and R
1Represent a hydrogen atom or halogen atom) and the protonated form of the logical formula IV chemical compound of B representative.
9, the dihydrate of 4-oxo-4H-1-.alpha.-5:6-benzopyran-2-carboxylic acid cimetidine salt.
10, the dihydrate of 4-oxo-4H-1-benzo thiapyran-2-carboxylic acid cimetidine salt.
11, carboxylic acid cimetidine salt 3-(4-chlorobenzene sulphonyl).
12, be used to prepare a kind of method that suppresses stomachial secretion and produce the pharmaceutical composition of gastric cells protective effect, comprise:
A) in 10: 1-1: 10(W/W) ratio, (wherein on behalf of an oxygen atom or sulphur atom and R, X represent a hydrogen atom, a hydroxyl, or C to mix a kind of chemical compound of logical formula II
1-4Alkyl or C
1-4Alkoxyl) or a kind of chemical compound of logical formula III (R wherein
1Represent a hydrogen atom or halogen atom) and cimetidine, add carrier known in the art and additive agent mixture then, perhaps
B) with a kind of chemical compound of logical formula I, wherein A represents the group of a kind of general formula (V) or (VI) (wherein X represents an oxygen atom or sulphur atom, and R represents a hydrogen atom, a hydroxyl, or C
1-4Alkyl or C
1-4Alkoxyl, and R
1Represent a hydrogen atom or halogen atom) and the protonated form of the logical formula IV chemical compound of B representative, mix with carrier known in the art and additive.
13, be used to prepare the method for logical formula I chemical compound, wherein A represents the group of a general formula (V) or (VI) (wherein X represents an oxygen atom or sulphur atom, and R represents a hydrogen atom, a hydroxyl, or C
1-4Alkyl or C
1-4Alkoxyl, and R
1Represent a hydrogen atom or halogen atom) and the logical formula IV chemical compound protonated form of B representative, comprise that (wherein on behalf of an oxygen atom or sulphur atom and R, X represent a hydrogen atom, a hydroxyl, or C with a kind of logical formula II chemical compound
1-4Alkyl or C
1-4Alkoxyl) or a kind of chemical compound of logical formula III (R wherein
1Represent a hydrogen atom or atom) with the reaction of a kind of chemical compound of logical formula IV.
14, be used for the treatment of and/or prevent the Therapeutic Method of the mammal esophagus of (comprising the people), stomach, duodenum inflammation and ulcer, comprise that (wherein X represents an oxygen atom or sulphur atom to the chemical compound that comprises a kind of logical formula II that gives a treatment of animal or human's body effective dose, represent a hydrogen atom with R, a hydroxyl, or C
1-4Alkyl or C
1-4Or a kind of chemical compound of logical formula III (R wherein alkoxyl),
1Represent a hydrogen atom or halogen atom) and a kind of chemical compound of logical formula IV 10: 1-1: mixture 10(w/w), perhaps a kind of chemical compound of logical formula I, wherein A represents group (wherein X, R and the R of a kind of general formula (V) or (VI)
1Define the same) and the protonated formation of the logical formula IV chemical compound of B representative and the Pharmaceutical composition of carrier known in the art and additive.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU4067/91 | 1991-12-20 | ||
| HU406791A HU209245B (en) | 1991-12-20 | 1991-12-20 | Process for producing new cimetidine derivatives, as well as new gastric acid secretion inhibiting and gastrocytoprotective pharmaceuitcal compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1075255A true CN1075255A (en) | 1993-08-18 |
Family
ID=10966768
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 92115369 Pending CN1075255A (en) | 1991-12-20 | 1992-12-19 | The new pharmaceutical composition of gastric cells protective effect is secreted and had to gastric acid inhibitory |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN1075255A (en) |
| HU (1) | HU209245B (en) |
| TW (1) | TW232015B (en) |
| WO (1) | WO1993012787A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997049679A1 (en) * | 1996-06-27 | 1997-12-31 | Ono Pharmaceutical Co., Ltd. | Aryl (sulfide, sulfoxide and sulfone) derivatives and drugs containing the same as the active ingredient |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0040489A1 (en) * | 1980-05-17 | 1981-11-25 | FISONS plc | Mixtures, salts, packages and pharmaceutical compositions containing 5-(2-hydroxypropoxy)-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid or a derivative thereof and an H2 receptor antagonist antihistamine |
| EP0156233A3 (en) * | 1984-03-19 | 1986-02-19 | Merck & Co. Inc. | Use of leukotriene antagonists for producing cytoprotective pharmaceutical compositions and process for producing cytoprotective pharmaceutical compositions |
| EP0389607A1 (en) * | 1988-09-14 | 1990-10-03 | Biota Scientific Management Pty. Ltd. | Chromone derivatives |
| HU203839B (en) * | 1989-07-14 | 1991-10-28 | Richter Gedeon Vegyeszet | Process for producing pharmaceutical composition containing acrylic acid derivatives |
-
1991
- 1991-12-20 HU HU406791A patent/HU209245B/en not_active IP Right Cessation
-
1992
- 1992-12-18 WO PCT/HU1992/000059 patent/WO1993012787A1/en active Application Filing
- 1992-12-19 CN CN 92115369 patent/CN1075255A/en active Pending
- 1992-12-21 TW TW81110294A patent/TW232015B/zh active
Also Published As
| Publication number | Publication date |
|---|---|
| HU914067D0 (en) | 1992-03-30 |
| WO1993012787A1 (en) | 1993-07-08 |
| HUT63955A (en) | 1993-11-29 |
| HU209245B (en) | 1994-04-28 |
| TW232015B (en) | 1994-10-11 |
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