CA1184120A - Pharmaceutical composition containing 1-(2-3'- carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole as active therapeutic agent - Google Patents
Pharmaceutical composition containing 1-(2-3'- carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole as active therapeutic agentInfo
- Publication number
- CA1184120A CA1184120A CA000391456A CA391456A CA1184120A CA 1184120 A CA1184120 A CA 1184120A CA 000391456 A CA000391456 A CA 000391456A CA 391456 A CA391456 A CA 391456A CA 1184120 A CA1184120 A CA 1184120A
- Authority
- CA
- Canada
- Prior art keywords
- composition
- oxyethyl
- nitroimidazole
- methyl
- carboxypropionyl
- 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
Classifications
-
- 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
- C07D233/66—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 hetero atoms or 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 to ring carbon atoms
- C07D233/91—Nitro radicals
- C07D233/92—Nitro radicals attached in position 4 or 5
- C07D233/94—Nitro radicals attached in position 4 or 5 with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to other ring members
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
ABSTRACT
Pharmaceutical composition and method adapted for the treatment of diseases caused by anaerobic microorganisms utilizing as the active ingredient 1-(2-3'-carboxypropionyl oxyethyl)-2 methyl-5-nitroimidazole or a pharmaceutically acceptable salt thereof.
Pharmaceutical composition and method adapted for the treatment of diseases caused by anaerobic microorganisms utilizing as the active ingredient 1-(2-3'-carboxypropionyl oxyethyl)-2 methyl-5-nitroimidazole or a pharmaceutically acceptable salt thereof.
Description
PHARMACEUTICAL COMPOSITION CONTAINING
1-(2-3'-CARBOXYPROPIONYL OXYETHYL)-2-METHYL
-5-NITROIMIDAZOLE AS ACTIVE THERAP~UTIC AGENT
AGAINST DIS ASES CAUSED BY ANAEROBIC GERMS
BACKGROUND AND SIJMMARY OF THE INVENTION
This invention relates ~o the deTivatives of imidazole 1-(2-3'-carboxypropionyl oxyethyl)-Z-methyl-5-nitroimidazole having the formula:
/ N
~ II C~
N02'~N /
CH2 CH2 0~ CH2--CH2-~--O~
and salts thereof with pharmaceutically acceptable inorganic or organic bases3 e.g., alkali metal, alkaline-earth metal/ ammonia, aliphatic amino acid, i.e., mono-or di-ethanolamine and the cyclic amine salts.
More particularly, the invention relates to pharmaceutical compositions containing these derivatives and methods of treatment therewith of infections caused by anaerobic bacteria,-e.g., Pep~ostreptococcus, Bacteroides fragilis, Bacteroides melaninoge~icus, Furobacterium, Clostridium perfringens and other species of Clostridium.
The salts of Compound I have the added 2S advantage of being soluble in water, which allows them to be used for parenteral administration.
~2~
The use of l-t2-3l-carboxypropionyl oxyethyl)-
1-(2-3'-CARBOXYPROPIONYL OXYETHYL)-2-METHYL
-5-NITROIMIDAZOLE AS ACTIVE THERAP~UTIC AGENT
AGAINST DIS ASES CAUSED BY ANAEROBIC GERMS
BACKGROUND AND SIJMMARY OF THE INVENTION
This invention relates ~o the deTivatives of imidazole 1-(2-3'-carboxypropionyl oxyethyl)-Z-methyl-5-nitroimidazole having the formula:
/ N
~ II C~
N02'~N /
CH2 CH2 0~ CH2--CH2-~--O~
and salts thereof with pharmaceutically acceptable inorganic or organic bases3 e.g., alkali metal, alkaline-earth metal/ ammonia, aliphatic amino acid, i.e., mono-or di-ethanolamine and the cyclic amine salts.
More particularly, the invention relates to pharmaceutical compositions containing these derivatives and methods of treatment therewith of infections caused by anaerobic bacteria,-e.g., Pep~ostreptococcus, Bacteroides fragilis, Bacteroides melaninoge~icus, Furobacterium, Clostridium perfringens and other species of Clostridium.
The salts of Compound I have the added 2S advantage of being soluble in water, which allows them to be used for parenteral administration.
~2~
The use of l-t2-3l-carboxypropionyl oxyethyl)-
2-methyl-5-nitroimidazole or salts may be used in combination with excipients or coatings normally used in pharmaceutical products.
DETAILED DESCRIPTION OF THE INVENTION
In clinical practice, the compounds of the present invention are administered parenterally, rectally or topically.
The compositions for oral administration include tablets, sugar-coated pills, dispersable powders or granules. In these solid mixtures, the active compound is administered together with at least one inert diluent such as calcium carbonate, potato starch, alginic acid, microcrystalline cellulose7 methyl cellulose, lactose or sucrose. The mixtures may also include additional substances other than the inert diluents, such as, for example, lubricating agents, e.g., magnesium stearate, stearic acid, talc. The liquid mixtures for oral administration include emulsions, solutions, suspensions, and pharmaceutically acceptable syrups and elixirs 9 also containing inert diluents. These mixtures may also contain additives such as humectant agents and sweetening, flavoring and aromatic suspensories and preservatives. The compositions may also be compounded for oral administration in capsule form with an absorbable material such as gelatine, containing the active substance with or without the addi~ion of diluents or excipien*s.
For parenteral administration, the compounds may be administered in a~ueous or non-aqueous sterile solutions, suspensions or emulsions. Some examples of non-aqueous solvents or suspensory media are: propylene glycol, polyethylene glycol, dioxilanes 3 vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. These mixtures may also contain additives
DETAILED DESCRIPTION OF THE INVENTION
In clinical practice, the compounds of the present invention are administered parenterally, rectally or topically.
The compositions for oral administration include tablets, sugar-coated pills, dispersable powders or granules. In these solid mixtures, the active compound is administered together with at least one inert diluent such as calcium carbonate, potato starch, alginic acid, microcrystalline cellulose7 methyl cellulose, lactose or sucrose. The mixtures may also include additional substances other than the inert diluents, such as, for example, lubricating agents, e.g., magnesium stearate, stearic acid, talc. The liquid mixtures for oral administration include emulsions, solutions, suspensions, and pharmaceutically acceptable syrups and elixirs 9 also containing inert diluents. These mixtures may also contain additives such as humectant agents and sweetening, flavoring and aromatic suspensories and preservatives. The compositions may also be compounded for oral administration in capsule form with an absorbable material such as gelatine, containing the active substance with or without the addi~ion of diluents or excipien*s.
For parenteral administration, the compounds may be administered in a~ueous or non-aqueous sterile solutions, suspensions or emulsions. Some examples of non-aqueous solvents or suspensory media are: propylene glycol, polyethylene glycol, dioxilanes 3 vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. These mixtures may also contain additives
-3-such as preservative, humectant, emulsi~ying and dispersant agents. They may also be sterilized, for example, by filtration through bacteria-retaining filters, by incorporation into the mixture of sterilizing agents, by irradiation or by heating. Ihey may also be manufac-tured in the ~orm of solid sterile mixtures which can be dissolved in sterile water or some other sterile injectable medium immediately be~ore use.
For topical application, the active substance may be incorporated into an appropriate vehicle such as a creme or unguent, or a pessary, ovule, or tablet for insertion into the vagina. The percentage of active ingredients in the mixtures of the present invention may vary in such a way that the ~roportion is appropriate for providing an adequate dosage with which to obtain the desired therapeutic effect.
It will be apparent that the composition may be administered at the same time in several different forms.
In human therapy, the mixtures must generally be adminis-tered and the pharmaceutical compositions formulated in such a way that, in the case of oral or topical adminis-tration9 0.250 to 3.0 g of active substance is administered per day, in the case of parenteral administration, 0.150 to 1.5 g per day; and rectally, 0.125 to 2.0 per day.
Thus, ~he solutions described below in Examples I to III, V~II and IX may be administered intravenously to adult humans ~500 mg every 8 hours) and 5 ml/min and to children under 12 (7O5 mg/kg-100 ml of solution) every eight hours at 5 ml/min.
The orally administrable dosages described below in Example IV to VI and X may be administered ~500 mg) three times a day for seven days or more.
The rectally administrable composition o~
Example VII may be administered to adults 1-3 times a day for three days and after the fourth day a suppository every ten hours for four days. In children under 12 a dosage
For topical application, the active substance may be incorporated into an appropriate vehicle such as a creme or unguent, or a pessary, ovule, or tablet for insertion into the vagina. The percentage of active ingredients in the mixtures of the present invention may vary in such a way that the ~roportion is appropriate for providing an adequate dosage with which to obtain the desired therapeutic effect.
It will be apparent that the composition may be administered at the same time in several different forms.
In human therapy, the mixtures must generally be adminis-tered and the pharmaceutical compositions formulated in such a way that, in the case of oral or topical adminis-tration9 0.250 to 3.0 g of active substance is administered per day, in the case of parenteral administration, 0.150 to 1.5 g per day; and rectally, 0.125 to 2.0 per day.
Thus, ~he solutions described below in Examples I to III, V~II and IX may be administered intravenously to adult humans ~500 mg every 8 hours) and 5 ml/min and to children under 12 (7O5 mg/kg-100 ml of solution) every eight hours at 5 ml/min.
The orally administrable dosages described below in Example IV to VI and X may be administered ~500 mg) three times a day for seven days or more.
The rectally administrable composition o~
Example VII may be administered to adults 1-3 times a day for three days and after the fourth day a suppository every ten hours for four days. In children under 12 a dosage
-4-of 500 mg may be administered three times a day for three days and after the fourth day a suppository every twelve hours for four days.
The compounds and compositions may also be used as prophylactic agents in surgery as well as renal and hepatic abscesses and gangrene.
It will be understood that the foregoing dosage ranges are optimal and that variations therein are permissible within the spirit of the invention in certain instances.
The invention is illustrated by the following non-limiting examples:
_AMPLE I.
In order to prepare an âqueous solution of 1-~2-3'-carboxypropionyl oxyethyl)-2-methyl-5-nitroimida~ole ~ at 35.0%, 35.0 g of the compound is dissolved in a mixture of diethanolamine ~13.56 g~ and water ~50 cc) and is brought to a volume of 100 cc with water.
The pH of the solution obtained is approxi-mately 6.
EXAMPLE II.
In order to prepare a 35.0% aqueous solution of the magnesium salt of ~I), 35.0 g of ~I) are made to react with basic-magnesium carbonate ~5.9 g) mixed with water ~70 cc), stirring and heating to approxima*ely 50C. When it has ceased giving off gas, it is brought to a volume of 100 cc with water and filtered. The solution obtained has a pH of approximately 5.7.
The compounds and compositions may also be used as prophylactic agents in surgery as well as renal and hepatic abscesses and gangrene.
It will be understood that the foregoing dosage ranges are optimal and that variations therein are permissible within the spirit of the invention in certain instances.
The invention is illustrated by the following non-limiting examples:
_AMPLE I.
In order to prepare an âqueous solution of 1-~2-3'-carboxypropionyl oxyethyl)-2-methyl-5-nitroimida~ole ~ at 35.0%, 35.0 g of the compound is dissolved in a mixture of diethanolamine ~13.56 g~ and water ~50 cc) and is brought to a volume of 100 cc with water.
The pH of the solution obtained is approxi-mately 6.
EXAMPLE II.
In order to prepare a 35.0% aqueous solution of the magnesium salt of ~I), 35.0 g of ~I) are made to react with basic-magnesium carbonate ~5.9 g) mixed with water ~70 cc), stirring and heating to approxima*ely 50C. When it has ceased giving off gas, it is brought to a volume of 100 cc with water and filtered. The solution obtained has a pH of approximately 5.7.
-5-EXAMPLE III.
In order to prepare a 25.0~ aqueous solution of the sodium salt of ~I), 35.0 g of (I) is made to react with sodium bicarbonate (10.76 g), mixing with water ~40 cc),.stirring and heaking to appToximately 50C. When it has ceased giving off gas, it is brought to a volume of 100 cc with water and filtered.
The solution obtained has a pH of approxi-mately 6..5.
EXAMPLE IV.
Tablets for oral administration? prepared by the usual *echnique, have the following composition:
1-(2-3~-carboxypropionyl oxyethyl)-2-methyl.-5-nitroimidazole 0.250 g 15 Starch 0.190 g Aerosil 200 0 050 g Magnesium stearate 0.025 g EXAMPLE V.
Table.ts for oral administration, prepared by the usual technique, have the following composition:
1-~2-3'-carboxypropionyl oxyethyl)- -2-methy.1-5-nitroimidazole 0.500 g Plasdone* 0.025 g Avicel*pH 102 0.130 g Talc 0.014 g Magnesium stearate 0.005 g Colorant 0.014 g * Trade Mark EXAMPLE VI.
Vaginal tablets, prepared by the usual technique, have the following composition:
l-(2-3'-carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole 0.500 g Cornstarch 0.683 g Alginic acid 0.050 g Aerosil 200 0.060 g Magnesium steaTate 0.0010 g EXAMPLE VII.
Vaginal ovules or suppositories, prepared by the usual technique, have the following composition:
l-~2-3'-carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole 20.83 g Sodium hydroxide solution 0.1 N 72.00 cc Manitol 30.00 g Timerosal 0.00025 g Distilled water sOq. 100.00 cc The solution is sterilized by means of 0.22 sterile 2~ membrane filter and is placed in ampul bottles to be - lyophilized from 5 cc into 3.0 cc portions. The product may be reconstituted for use with 3 cc of sterile water ~or injection.
~EXAMPLE VIII
A solution for injection:
8 g of micronized powder of 1-(2-3'-carboxy-propionyl oxyethyl~-2-methyl-5-nitroimidazole is intro-duced aseptically into an ampul bottle. Then the product is steriliz-ed at 100C for one hour. Meanwhile a solution is prepared with the following composition:
,~
Sodium acetate amino acid or 2 amino ethanol 20 g Distilled water s.q. 100 cc The solution thus obtained is sterilized by filtration through a 0.22 membrane; 20 cc of this solution is taken and the content of the ampul bottle dissolved. The solution obtained should be used no later than two hours following its preparation.
EXAMPLE IX
Suspension for oral administration:
1-(2-3t-carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole 1.5 g Glass sugar 18 g Sodium nipagin 0.108 g 15 Sodium nipasol 0.012 g Sodium saccharin 0.03 g 50dium dibasic phosphate 0.1983 g Sodium monobasic phosphate 0.1017 g Carboxymethyl cellulose 0.18 g 20 Manitol 3.87 g Total 24 g The mixture obtained is reconstituted with water to a volume of 60 ml at the time of use. This suspension should be used within seven days at most and the remainder discarded.
"
,,~,,~,, -8~
EXAMPLE X
Unguent foT topical preparation:
1-(2-3'-carbosypropionyl oxyethyl)-Z-methyl-5-nitroimidazole 0.750 g 5 Cetyl alcohol 10.5 g Stearilic alcohol 9.3 g Liquid vaseline 25.5 g Glycerine 15 g Solid vaseline 33.9 g 10 Nipagin* 0.36 g Nipasol* 0.09 g Span*60 2.3 g Tween*60 2.3 g * Trade Mark
In order to prepare a 25.0~ aqueous solution of the sodium salt of ~I), 35.0 g of (I) is made to react with sodium bicarbonate (10.76 g), mixing with water ~40 cc),.stirring and heaking to appToximately 50C. When it has ceased giving off gas, it is brought to a volume of 100 cc with water and filtered.
The solution obtained has a pH of approxi-mately 6..5.
EXAMPLE IV.
Tablets for oral administration? prepared by the usual *echnique, have the following composition:
1-(2-3~-carboxypropionyl oxyethyl)-2-methyl.-5-nitroimidazole 0.250 g 15 Starch 0.190 g Aerosil 200 0 050 g Magnesium stearate 0.025 g EXAMPLE V.
Table.ts for oral administration, prepared by the usual technique, have the following composition:
1-~2-3'-carboxypropionyl oxyethyl)- -2-methy.1-5-nitroimidazole 0.500 g Plasdone* 0.025 g Avicel*pH 102 0.130 g Talc 0.014 g Magnesium stearate 0.005 g Colorant 0.014 g * Trade Mark EXAMPLE VI.
Vaginal tablets, prepared by the usual technique, have the following composition:
l-(2-3'-carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole 0.500 g Cornstarch 0.683 g Alginic acid 0.050 g Aerosil 200 0.060 g Magnesium steaTate 0.0010 g EXAMPLE VII.
Vaginal ovules or suppositories, prepared by the usual technique, have the following composition:
l-~2-3'-carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole 20.83 g Sodium hydroxide solution 0.1 N 72.00 cc Manitol 30.00 g Timerosal 0.00025 g Distilled water sOq. 100.00 cc The solution is sterilized by means of 0.22 sterile 2~ membrane filter and is placed in ampul bottles to be - lyophilized from 5 cc into 3.0 cc portions. The product may be reconstituted for use with 3 cc of sterile water ~or injection.
~EXAMPLE VIII
A solution for injection:
8 g of micronized powder of 1-(2-3'-carboxy-propionyl oxyethyl~-2-methyl-5-nitroimidazole is intro-duced aseptically into an ampul bottle. Then the product is steriliz-ed at 100C for one hour. Meanwhile a solution is prepared with the following composition:
,~
Sodium acetate amino acid or 2 amino ethanol 20 g Distilled water s.q. 100 cc The solution thus obtained is sterilized by filtration through a 0.22 membrane; 20 cc of this solution is taken and the content of the ampul bottle dissolved. The solution obtained should be used no later than two hours following its preparation.
EXAMPLE IX
Suspension for oral administration:
1-(2-3t-carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole 1.5 g Glass sugar 18 g Sodium nipagin 0.108 g 15 Sodium nipasol 0.012 g Sodium saccharin 0.03 g 50dium dibasic phosphate 0.1983 g Sodium monobasic phosphate 0.1017 g Carboxymethyl cellulose 0.18 g 20 Manitol 3.87 g Total 24 g The mixture obtained is reconstituted with water to a volume of 60 ml at the time of use. This suspension should be used within seven days at most and the remainder discarded.
"
,,~,,~,, -8~
EXAMPLE X
Unguent foT topical preparation:
1-(2-3'-carbosypropionyl oxyethyl)-Z-methyl-5-nitroimidazole 0.750 g 5 Cetyl alcohol 10.5 g Stearilic alcohol 9.3 g Liquid vaseline 25.5 g Glycerine 15 g Solid vaseline 33.9 g 10 Nipagin* 0.36 g Nipasol* 0.09 g Span*60 2.3 g Tween*60 2.3 g * Trade Mark
Claims (11)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A method of preparing a pharmaceutical composi-tion for the treatment of anaerobic bacterial infections compris-ing admixing a therapeutically effective amount of a compound selected from the group consisting of 1-(2,3'-carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole and salts thereof with pharmaceutically acceptable bases or acids and a pharmaceut-ically acceptable carrier.
2. A pharmaceutical composition in unit dosage form consisting essentially of a compound selected from the group consisting of 1-(2,3'-carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole and salts thereof with pharmaceutically acceptable bases or acids and a pharmaceutically acceptable carrier, said compound being present in an amount therapeutically effective for the treatment of anaerobic baterial infections when adminis-tered to a human in need thereof.
3. The composition of claim 2 wherein said bases are derived from ammonia, alkali or alkaline earth metals.
4. The composition of claim 2, wherein said acids are aliphatic amino acids.
5. The composition of claim 2, wherein the amount of said compound present therein is therapeutically effective for the treatment of infections caused by Peptostreptococcus, Bacteroides fragilis, Bacteroides melaninoenicus, Furobacterium, Clostridium perfringens and Clostridium Sp.
6. The composition of claim 2 in a form suitable for parenteral administration.
7. The composition of claim 2 suitable for oral administration.
8. The composition of claim 2 suitable for topical administration.
9. The composition of claim 2 suitable for rectal administration.
10. The composition of claim 2 suitable for vaginal administration.
11. A composition particularly adapted for prophylaxis in surgery comprising, as an active ingredient, 1-(2,3'-carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole in an amount effective for the prevention of anaerobic bacterial infections, and a pharmaceutically acceptable carrier.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| MX9,191 | 1980-12-03 | ||
| MX809191U MX6789E (en) | 1980-12-03 | 1980-12-03 | PROCEDURE FOR THE PREPARATION OF ANTIBACTERIAL COMPOSITIONS BASED ON 1- (2,3'-CARBOXIPROPIONILOXIETIL) -2-METHYL-5-NITROIMIDAZOLE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1184120A true CA1184120A (en) | 1985-03-19 |
Family
ID=19741552
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000391456A Expired CA1184120A (en) | 1980-12-03 | 1981-12-03 | Pharmaceutical composition containing 1-(2-3'- carboxypropionyl oxyethyl)-2-methyl-5-nitroimidazole as active therapeutic agent |
Country Status (12)
| Country | Link |
|---|---|
| JP (1) | JPS57188518A (en) |
| BE (1) | BE891284A (en) |
| CA (1) | CA1184120A (en) |
| CH (1) | CH652597A5 (en) |
| DE (1) | DE3147959A1 (en) |
| FR (1) | FR2494993A1 (en) |
| GB (1) | GB2089208A (en) |
| IT (1) | IT1145989B (en) |
| LU (1) | LU83802A1 (en) |
| MX (1) | MX6789E (en) |
| NL (1) | NL8105449A (en) |
| PT (1) | PT74056B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1194283B (en) * | 1983-06-21 | 1988-09-14 | Isnardi Pietro & C Spa | WATER SOLUBLE DERIVATIVE OF 1- (2-HYDROXYETHYL) -2-METHYL-5-NITRO-IMIDAZOLE FOR THERAPEUTIC ACTIVITY, PROCEDURE FOR ITS PREPARATION AND RELATED PHARMACEUTICAL COMPOSITIONS |
| IL100323A0 (en) * | 1990-12-11 | 1992-09-06 | Brocades Pharma Bv | Heterocyclic carboxylic esters,their preparation and their use for the preparation of gastro-intestinal medicines |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB983123A (en) * | 1961-07-07 | 1965-02-10 | Rhone Poulenc Sa | Improvements in or relating to imidazole derivatives |
-
1980
- 1980-12-03 MX MX809191U patent/MX6789E/en unknown
-
1981
- 1981-11-27 PT PT74056A patent/PT74056B/en unknown
- 1981-11-27 IT IT12688/81A patent/IT1145989B/en active
- 1981-11-30 BE BE//206684A patent/BE891284A/en not_active IP Right Cessation
- 1981-12-01 CH CH7680/81A patent/CH652597A5/en not_active IP Right Cessation
- 1981-12-01 LU LU83802A patent/LU83802A1/en unknown
- 1981-12-02 NL NL8105449A patent/NL8105449A/en not_active Application Discontinuation
- 1981-12-02 GB GB8136309A patent/GB2089208A/en not_active Withdrawn
- 1981-12-02 FR FR8122594A patent/FR2494993A1/en active Pending
- 1981-12-03 DE DE19813147959 patent/DE3147959A1/en not_active Withdrawn
- 1981-12-03 CA CA000391456A patent/CA1184120A/en not_active Expired
- 1981-12-03 JP JP56193768A patent/JPS57188518A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| MX6789E (en) | 1986-07-21 |
| PT74056B (en) | 1983-04-26 |
| PT74056A (en) | 1981-12-01 |
| IT1145989B (en) | 1986-11-12 |
| NL8105449A (en) | 1982-07-01 |
| BE891284A (en) | 1982-06-01 |
| IT8112688A0 (en) | 1981-11-27 |
| LU83802A1 (en) | 1983-09-01 |
| FR2494993A1 (en) | 1982-06-04 |
| CH652597A5 (en) | 1985-11-29 |
| DE3147959A1 (en) | 1983-03-24 |
| JPS57188518A (en) | 1982-11-19 |
| GB2089208A (en) | 1982-06-23 |
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