CA2036091A1 - Pharmaceutical composition - Google Patents
Pharmaceutical compositionInfo
- Publication number
- CA2036091A1 CA2036091A1 CA002036091A CA2036091A CA2036091A1 CA 2036091 A1 CA2036091 A1 CA 2036091A1 CA 002036091 A CA002036091 A CA 002036091A CA 2036091 A CA2036091 A CA 2036091A CA 2036091 A1 CA2036091 A1 CA 2036091A1
- Authority
- CA
- Canada
- Prior art keywords
- bisoprolol
- pharmaceutical composition
- potassium channel
- acceptable salts
- channel activator
- 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.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
Merck Patent Gesellschaft mit beschrankter Haftung D a r m s t a d t ABSTRACT
The invention relates to a pharmaceutical com-position containing bisoprolol and/or one of its physio-logically acceptable salts and a potassium channel activator.
The invention relates to a pharmaceutical com-position containing bisoprolol and/or one of its physio-logically acceptable salts and a potassium channel activator.
Description
Merck Patent Gesellschaft mit beschr~nkter Haftung D a r m s t a d t Pharmaceutical composition S ~he invention relates to a new pharmaceutical composition containing bisoprolol and/or one of its physiologically acceptable salts and a potassium channel activator.
This new composition acts to lower blood pressure and can also be used for ~reating asthma, disturbances of peripheral blood flow, heart failure and/or angina pectoris.
The object of the invention was to provide new medicaments in the form of pharmaceutical compositions which have better properties than known medicaments which can be used for the ~ame purposes.
This object has been achieved by the discovery of the new composition. Bisoprolol = (+)-1-p-~2-isopropoxy-ethoxymethyl)-phenoxy-3-isopropylamino-2-propanol is disclosed in German Offenlegungsschrift 2,645,710. The preferred salts of bisoprolol are the hydrochloride and the hemifumarate.
EP-A2-0,323,745 has already described pharmaceut-ical products which contain combinations of potassium channel activators with ~-receptor blockers. However, bisoprolol is not mentioned among the ~-receptor blockers specified therein. Compared with the products specified therein, the present new compositions are distinguished by high ~1-selectivity and a long duration of action.
Potassium channel activators are describPd, for example, in EP-A-0,205,292, EP-A-0,214,818, EP-A-0,250,077, GB-A-1,489,879, EP-A-0,112,776, EP-A-0,273,262, EP-A-0,277,612, EP-A-0,277,612, EP-A-0,340,718 and EP-A-0,346,724.
Preferred potassium channel activators are those of the formula I
This new composition acts to lower blood pressure and can also be used for ~reating asthma, disturbances of peripheral blood flow, heart failure and/or angina pectoris.
The object of the invention was to provide new medicaments in the form of pharmaceutical compositions which have better properties than known medicaments which can be used for the ~ame purposes.
This object has been achieved by the discovery of the new composition. Bisoprolol = (+)-1-p-~2-isopropoxy-ethoxymethyl)-phenoxy-3-isopropylamino-2-propanol is disclosed in German Offenlegungsschrift 2,645,710. The preferred salts of bisoprolol are the hydrochloride and the hemifumarate.
EP-A2-0,323,745 has already described pharmaceut-ical products which contain combinations of potassium channel activators with ~-receptor blockers. However, bisoprolol is not mentioned among the ~-receptor blockers specified therein. Compared with the products specified therein, the present new compositions are distinguished by high ~1-selectivity and a long duration of action.
Potassium channel activators are describPd, for example, in EP-A-0,205,292, EP-A-0,214,818, EP-A-0,250,077, GB-A-1,489,879, EP-A-0,112,776, EP-A-0,273,262, EP-A-0,277,612, EP-A-0,277,612, EP-A-0,340,718 and EP-A-0,346,724.
Preferred potassium channel activators are those of the formula I
2 2~3 6 0 ~X~
~ 0~
R7 \ Rl in which X-Y is =CH-CHRa-, =CR4-CR3A- or =CH-CA(OA)-, and, if the radical R5 is neither completely nor parti-ally hydrogenated, also =C4-CHR3_ or =CH-CH(OA)-, R1 is A, R2 and R8 are each H or A, R1 and R2 together are also alkylene with 3-6 C atoms R3 is OH, or OAc, R4 is H, R3 and R4 together are also a bond, R5 is a pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, oxo-dihydro-pyridyl, oxo-dihydro-pyridazinyl, oxo-dihydro-pyrimidinyl, oxo-dihydro-pyrazinyl, 3H- or 5H-2-pyrrolinon-1-yl, 2H-1-isoquinolinon-2-yl, 2H-l-phthalazinon-2~
yl, 3H-4-quinazolinon-3-yl, or lH-2-thio-pyridon-l-yl radical, each of which is - unsubstituted or substituted once or twice by A, F, Cl, Br, I, OH, OA, OAc, NO2, NH2, AcNH, HOOC and/or AOOC, it also being possible for these radicals to be completely or partially hydrogenated, R6 and R7 are each H, A, HO, AO, CHO, ACO, ACS, HOOC, AOOC, AO-CS, ACOO, A-CS-O, hydroxyalkyl, mercaptoalkyl, NO2, NH2, NHA, NA2, CN, F, Cl, Br, I, CF3, ASO, ASO2, AO-SO, AO-SO2, AcNH, AO-CO-NH, H2NSO, HANSO, A2NSO, H2NSO2, HANSO2, A2NSO2, H2NCO, HANCO, A2NCO, H2NCS, HANCS, A2NCS, ASONH, ASO2NH, AOSONH, AOSO2NH, ACO-alkyl, nitroalkyl, cyanoalkyl, A-C(=NOH) or A-C(=NNH2), Z is a bond, O, S or NH, R7 is also pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl, A is alkyl with 1-6 C atoms (where several groups A can, independently of one another, be different alkyl groups), -alkyl- is alkylene with 1-6 C atoms and Ac is alkanoyl with 1-8 C atoms or aroyl with 7-11 C atoms, and/or one of the physiologically acceptable salts thereof.
Some of the compounds of the formula I are known (compare, for example, EP-A-0,273,262).
Preferred compounds of the formula I are those in which the radicals Rl and R2 are each CH3, the radical R7 is H and/or the radical R6 is CN, with the radical R6 preferably being in the 6 position. The group X-Y is preferably =CR4-CR3A- [especially =CH-C(OH)A- or =C=CA-]
or else, if the radical R5 is neither completely nor partially hydrogenated, =CR4-CHR3- (especially =CH-CHOH-or =C=CH-).
The group R5-Z is preferably lH-2-pyridon-1-yl, 2-hydroxy-4-pyridyloxy, 6-hydroxy-3-pyridazinyloxy, 1,6-dihydro-1-methyl- or 1,6-dihydro-1-ethyl-6-oxo-3-pyridazinyloxy.
Specific preferred compounds of the ~ormula I are 2,2-dimethyl-4-(lH-2-pyridon-1-yl)-6-cyano-3-chromanol ~Ia), especially its (3S,4R~ enantiomer, 2,2-dimethyl-4-(lH-2-pyridon-1-yl)-6-cyano-2H-chromene (Ib), 2,2-di-methyl-4-(6-hydroxy-3-pyridazinyloxy)-6-cyano-3-chrom-anol, especially its (3S,4R) enantiomer, 2,2,3-trimethyl-4-(6-hydroxy-3-pyridazinyloxy)-6-cyano-3-chromanol, especially its (3S,4R) enantiomer, 2,2-dimethyl-4-(1,6-dihydro-1-methyl-6-oxo-3-pyridazinyloxy~-6-cyano-3-chromanol (Ic), especially its (3S,4R) enantiomer, 2,2,3-trimethyl-4-(1,6-dihydro-1-methyl-6-oxo-3-pyridazinyl-oxy)-6-cyano-3-chromanol, especially its (3S,4R) enantiomer.
It is remarkable that the action of the said potassium channel activators in lowering blood press~re is distinctly enhanced by concurrent administration of bisoprolol. The action of the combination is greater than can be expected after estimation of the action of the individual components. This (synergistic) effect can be found, for example, in standard tests on anaesthetized or conscious rats, dogs, cats, monkeys or minipigs, for example by methods as described in EP-A2-0,323,745.
The new pharmaceutical composition can be pre-pared by converting bisoprolol and/or one of its physio-logically acceptable salts and (at least) one potassiumchannel activator, preferably a compound of the formula I, together with at least one solid, liquid or semi-liquid vehicle or auxiliary into a suitable dosage form. The compositions obtained in this way can be used as medicaments in human or veterinary medicine, espe-cially for lowering blood pressure. Suitable vehicles are organic or inorganic substances which are suitable for enteral (for example oral, sublingual or rectal), parent-eral or topical (for example transdermal) administration and do not react with the new compounds, for example water, vegetable oils, benzyl alcohols, polyethylene glycols, glycerol triacetate and other fatty acid glycer-ides, gelatin, soya lecithin, carbohydrates such as lactose or starch, magnesium stearate, talc or cellulose.
Used f~r oral administration are, in particular, tablets, coated tablets, capsules, syrups, solutions or drops, for rectal administration are suppositories, for parenteral administration are solutions, preferably oily or aqueous solutions, as well as suspensions, emulsions or implants, and for topical administration are ointments, creams or plasters. The active substances can also be freeze-dried and the resulting lyophilisates used, for example, for preparing in~ection products. The compositions can be sterilized and/or contain auxiliaries such as preserv-atives, stabilizers and/or wetting agents, emulsifiers,salts to influence the osmotic pressure, buffer substanc-es, colorants and/or flavourings. They can also contain other active substances, for example other substances acting ~o lower blood pressure, or diuretics.
~ 0~
R7 \ Rl in which X-Y is =CH-CHRa-, =CR4-CR3A- or =CH-CA(OA)-, and, if the radical R5 is neither completely nor parti-ally hydrogenated, also =C4-CHR3_ or =CH-CH(OA)-, R1 is A, R2 and R8 are each H or A, R1 and R2 together are also alkylene with 3-6 C atoms R3 is OH, or OAc, R4 is H, R3 and R4 together are also a bond, R5 is a pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, oxo-dihydro-pyridyl, oxo-dihydro-pyridazinyl, oxo-dihydro-pyrimidinyl, oxo-dihydro-pyrazinyl, 3H- or 5H-2-pyrrolinon-1-yl, 2H-1-isoquinolinon-2-yl, 2H-l-phthalazinon-2~
yl, 3H-4-quinazolinon-3-yl, or lH-2-thio-pyridon-l-yl radical, each of which is - unsubstituted or substituted once or twice by A, F, Cl, Br, I, OH, OA, OAc, NO2, NH2, AcNH, HOOC and/or AOOC, it also being possible for these radicals to be completely or partially hydrogenated, R6 and R7 are each H, A, HO, AO, CHO, ACO, ACS, HOOC, AOOC, AO-CS, ACOO, A-CS-O, hydroxyalkyl, mercaptoalkyl, NO2, NH2, NHA, NA2, CN, F, Cl, Br, I, CF3, ASO, ASO2, AO-SO, AO-SO2, AcNH, AO-CO-NH, H2NSO, HANSO, A2NSO, H2NSO2, HANSO2, A2NSO2, H2NCO, HANCO, A2NCO, H2NCS, HANCS, A2NCS, ASONH, ASO2NH, AOSONH, AOSO2NH, ACO-alkyl, nitroalkyl, cyanoalkyl, A-C(=NOH) or A-C(=NNH2), Z is a bond, O, S or NH, R7 is also pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl, A is alkyl with 1-6 C atoms (where several groups A can, independently of one another, be different alkyl groups), -alkyl- is alkylene with 1-6 C atoms and Ac is alkanoyl with 1-8 C atoms or aroyl with 7-11 C atoms, and/or one of the physiologically acceptable salts thereof.
Some of the compounds of the formula I are known (compare, for example, EP-A-0,273,262).
Preferred compounds of the formula I are those in which the radicals Rl and R2 are each CH3, the radical R7 is H and/or the radical R6 is CN, with the radical R6 preferably being in the 6 position. The group X-Y is preferably =CR4-CR3A- [especially =CH-C(OH)A- or =C=CA-]
or else, if the radical R5 is neither completely nor partially hydrogenated, =CR4-CHR3- (especially =CH-CHOH-or =C=CH-).
The group R5-Z is preferably lH-2-pyridon-1-yl, 2-hydroxy-4-pyridyloxy, 6-hydroxy-3-pyridazinyloxy, 1,6-dihydro-1-methyl- or 1,6-dihydro-1-ethyl-6-oxo-3-pyridazinyloxy.
Specific preferred compounds of the ~ormula I are 2,2-dimethyl-4-(lH-2-pyridon-1-yl)-6-cyano-3-chromanol ~Ia), especially its (3S,4R~ enantiomer, 2,2-dimethyl-4-(lH-2-pyridon-1-yl)-6-cyano-2H-chromene (Ib), 2,2-di-methyl-4-(6-hydroxy-3-pyridazinyloxy)-6-cyano-3-chrom-anol, especially its (3S,4R) enantiomer, 2,2,3-trimethyl-4-(6-hydroxy-3-pyridazinyloxy)-6-cyano-3-chromanol, especially its (3S,4R) enantiomer, 2,2-dimethyl-4-(1,6-dihydro-1-methyl-6-oxo-3-pyridazinyloxy~-6-cyano-3-chromanol (Ic), especially its (3S,4R) enantiomer, 2,2,3-trimethyl-4-(1,6-dihydro-1-methyl-6-oxo-3-pyridazinyl-oxy)-6-cyano-3-chromanol, especially its (3S,4R) enantiomer.
It is remarkable that the action of the said potassium channel activators in lowering blood press~re is distinctly enhanced by concurrent administration of bisoprolol. The action of the combination is greater than can be expected after estimation of the action of the individual components. This (synergistic) effect can be found, for example, in standard tests on anaesthetized or conscious rats, dogs, cats, monkeys or minipigs, for example by methods as described in EP-A2-0,323,745.
The new pharmaceutical composition can be pre-pared by converting bisoprolol and/or one of its physio-logically acceptable salts and (at least) one potassiumchannel activator, preferably a compound of the formula I, together with at least one solid, liquid or semi-liquid vehicle or auxiliary into a suitable dosage form. The compositions obtained in this way can be used as medicaments in human or veterinary medicine, espe-cially for lowering blood pressure. Suitable vehicles are organic or inorganic substances which are suitable for enteral (for example oral, sublingual or rectal), parent-eral or topical (for example transdermal) administration and do not react with the new compounds, for example water, vegetable oils, benzyl alcohols, polyethylene glycols, glycerol triacetate and other fatty acid glycer-ides, gelatin, soya lecithin, carbohydrates such as lactose or starch, magnesium stearate, talc or cellulose.
Used f~r oral administration are, in particular, tablets, coated tablets, capsules, syrups, solutions or drops, for rectal administration are suppositories, for parenteral administration are solutions, preferably oily or aqueous solutions, as well as suspensions, emulsions or implants, and for topical administration are ointments, creams or plasters. The active substances can also be freeze-dried and the resulting lyophilisates used, for example, for preparing in~ection products. The compositions can be sterilized and/or contain auxiliaries such as preserv-atives, stabilizers and/or wetting agents, emulsifiers,salts to influence the osmotic pressure, buffer substanc-es, colorants and/or flavourings. They can also contain other active substances, for example other substances acting ~o lower blood pressure, or diuretics.
The composition~ according to the invention are used for lowering blood pressure and/or for controlling diseases. They are, as a rule, administered for the therapy and/or prophylaxis of asthma, disorders of the cardiovascular system, especially congestive heart failure, angina pectoris, peripheral or cerebral vessel disorders and pathological states a~sociated with high blood pressure, in analogy to known substances acting to lower the blood pressure, e~pecially the ~-receptor blockers or the potassium channel activators themselves.
The dosages of the compounds of the formula I or the salts thereof are preferably between about 0.1 mg and 50 mg, especially 0.2 and 10 mg, very particularly preferably between 0.1 and 5 mg, per dosage unit.
Bisoprolol is preferably used in dosages between about 1 and about 100 mg, especially between ~ and 20 mg, per dosage unit. The daily dosage of the compounds of the formula I or the salts thereof is preferably between about 0.001 and 1, in particular between 0.002 and 0.2 mg/kg of body weight, and those of bisoprolol are preferably between about 0.02 and 0.2 mg/kg of body weight. The specific dose for each particular patient depends, however, on a wide variety of factors, for example on the activity of the specific compound em-ployedj the age, body weight, general state of health, sex, the diet, the time and route of administration, the rate of elimination, drug combination and severity of the particular disease for which the therapy is applied. Oral administration is preferred.
The components of the new pharmaceutical composi-tion are preferably administered in combination. However, they can also be administered singly, concurrently or successively.
Example 1: Tablets A mixture of 20 g of Ia, 100 g of bisoprolol hemifumarate, 4 kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate is compressed in a customary manner to give tablets such that each tablet contains 1 mg of Ia and 5 mg of bisoprolol hemifumarate.
Example 2: Coated tablets Tablets are compressed in analogy to Example A
and then coated in a conventional manner with a coating composed of sucrose, potato starch, talc, tragacanth and colorant.
Example 3: Capsules A screened mixture of 30 g of Ib, 100 g of bisoprolol hemifumarate and 6 kg of lactose is used to fill hard gelatin capsules in a customary manner such that each capsule contains 0.3 mg of Ib and l mg of bisoprolol hemifumarate.
Example D: Ampoules A solution of 2 g of Ic and 20 g of bisoprolol hemifumarate in 30 l of double-distilled water is fil-tered sterile, dispensed into ampoules, freeze-dried under sterile conditions and sealed sterile. Each ampoule contains 0.1 mg of Ic and 1 mg of bisoprolol hemifumarate.
The dosages of the compounds of the formula I or the salts thereof are preferably between about 0.1 mg and 50 mg, especially 0.2 and 10 mg, very particularly preferably between 0.1 and 5 mg, per dosage unit.
Bisoprolol is preferably used in dosages between about 1 and about 100 mg, especially between ~ and 20 mg, per dosage unit. The daily dosage of the compounds of the formula I or the salts thereof is preferably between about 0.001 and 1, in particular between 0.002 and 0.2 mg/kg of body weight, and those of bisoprolol are preferably between about 0.02 and 0.2 mg/kg of body weight. The specific dose for each particular patient depends, however, on a wide variety of factors, for example on the activity of the specific compound em-ployedj the age, body weight, general state of health, sex, the diet, the time and route of administration, the rate of elimination, drug combination and severity of the particular disease for which the therapy is applied. Oral administration is preferred.
The components of the new pharmaceutical composi-tion are preferably administered in combination. However, they can also be administered singly, concurrently or successively.
Example 1: Tablets A mixture of 20 g of Ia, 100 g of bisoprolol hemifumarate, 4 kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate is compressed in a customary manner to give tablets such that each tablet contains 1 mg of Ia and 5 mg of bisoprolol hemifumarate.
Example 2: Coated tablets Tablets are compressed in analogy to Example A
and then coated in a conventional manner with a coating composed of sucrose, potato starch, talc, tragacanth and colorant.
Example 3: Capsules A screened mixture of 30 g of Ib, 100 g of bisoprolol hemifumarate and 6 kg of lactose is used to fill hard gelatin capsules in a customary manner such that each capsule contains 0.3 mg of Ib and l mg of bisoprolol hemifumarate.
Example D: Ampoules A solution of 2 g of Ic and 20 g of bisoprolol hemifumarate in 30 l of double-distilled water is fil-tered sterile, dispensed into ampoules, freeze-dried under sterile conditions and sealed sterile. Each ampoule contains 0.1 mg of Ic and 1 mg of bisoprolol hemifumarate.
Claims (3)
1. Pharmaceutical composition containing bisoprolol and/or one of its physiologically acceptable salts and a potassium channel activator.
2. Process for the preparation of a pharmaceutical composition, characterized in that bisoprolol and/or one of its physiologically acceptable salts and a potassium channel activator are converted together with at least one solid, liquid or semi-liquid vehicle or auxiliary into a suitable dosage form.
3. Use of a pharmaceutical composition containing bisoprolol and/or one of its physiologically acceptable salts and a potassium channel activator for lowering blood pressure and/or for controlling diseases.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4004268A DE4004268A1 (en) | 1990-02-13 | 1990-02-13 | PHARMACEUTICAL PREPARATION |
DEP4004268.5 | 1990-02-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2036091A1 true CA2036091A1 (en) | 1991-08-14 |
Family
ID=6399970
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002036091A Abandoned CA2036091A1 (en) | 1990-02-13 | 1991-02-11 | Pharmaceutical composition |
Country Status (16)
Country | Link |
---|---|
EP (1) | EP0442141B1 (en) |
JP (1) | JPH04234813A (en) |
KR (1) | KR910015294A (en) |
AT (1) | ATE102031T1 (en) |
AU (1) | AU642961B2 (en) |
CA (1) | CA2036091A1 (en) |
DE (2) | DE4004268A1 (en) |
DK (1) | DK0442141T3 (en) |
ES (1) | ES2062287T3 (en) |
HU (1) | HU208483B (en) |
IE (1) | IE64207B1 (en) |
IL (1) | IL97211A (en) |
NO (1) | NO910566L (en) |
NZ (1) | NZ237092A (en) |
PT (1) | PT96719A (en) |
ZA (1) | ZA911074B (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4209071A1 (en) * | 1992-03-20 | 1993-09-23 | Merck Patent Gmbh | PHARMACEUTICAL PREPARATION |
US5574049A (en) * | 1994-07-22 | 1996-11-12 | Sandoz Ltd. | 2,2-dialkyl- and 2,2-dialkyl-3,4-dihydro-3-hydroxy-2H-1-benzopyrans |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8800199D0 (en) * | 1988-01-06 | 1988-02-10 | Beecham Group Plc | Pharmaceutical preparation |
-
1990
- 1990-02-13 DE DE4004268A patent/DE4004268A1/en not_active Withdrawn
- 1990-12-24 DK DK90125410.2T patent/DK0442141T3/en active
- 1990-12-24 AT AT90125410T patent/ATE102031T1/en not_active IP Right Cessation
- 1990-12-24 EP EP90125410A patent/EP0442141B1/en not_active Expired - Lifetime
- 1990-12-24 ES ES90125410T patent/ES2062287T3/en not_active Expired - Lifetime
- 1990-12-24 DE DE90125410T patent/DE59004798D1/en not_active Expired - Fee Related
-
1991
- 1991-02-06 KR KR1019910002009A patent/KR910015294A/en not_active Application Discontinuation
- 1991-02-08 PT PT96719A patent/PT96719A/en not_active Application Discontinuation
- 1991-02-11 CA CA002036091A patent/CA2036091A1/en not_active Abandoned
- 1991-02-11 IL IL9721191A patent/IL97211A/en active IP Right Review Request
- 1991-02-12 NO NO91910566A patent/NO910566L/en unknown
- 1991-02-12 NZ NZ237092A patent/NZ237092A/en unknown
- 1991-02-12 IE IE47391A patent/IE64207B1/en not_active IP Right Cessation
- 1991-02-12 HU HU91463A patent/HU208483B/en not_active IP Right Cessation
- 1991-02-13 JP JP3104067A patent/JPH04234813A/en active Pending
- 1991-02-13 AU AU71029/91A patent/AU642961B2/en not_active Ceased
- 1991-02-13 ZA ZA911074A patent/ZA911074B/en unknown
Also Published As
Publication number | Publication date |
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PT96719A (en) | 1991-10-31 |
EP0442141B1 (en) | 1994-03-02 |
NO910566L (en) | 1991-08-14 |
DK0442141T3 (en) | 1994-03-28 |
HU208483B (en) | 1993-11-29 |
ATE102031T1 (en) | 1994-03-15 |
DE4004268A1 (en) | 1991-08-14 |
ES2062287T3 (en) | 1994-12-16 |
IL97211A0 (en) | 1992-08-18 |
IL97211A (en) | 1995-07-31 |
IE64207B1 (en) | 1995-07-12 |
JPH04234813A (en) | 1992-08-24 |
AU7102991A (en) | 1991-08-15 |
DE59004798D1 (en) | 1994-04-07 |
IE910473A1 (en) | 1991-08-14 |
ZA911074B (en) | 1991-11-27 |
HUT59593A (en) | 1992-06-29 |
AU642961B2 (en) | 1993-11-04 |
EP0442141A1 (en) | 1991-08-21 |
KR910015294A (en) | 1991-09-30 |
HU910463D0 (en) | 1991-08-28 |
NO910566D0 (en) | 1991-02-12 |
NZ237092A (en) | 1993-01-27 |
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