DE10004651A1 - Kombination von blutdrucksenkenden Wirkstoffen mit Wirkstoffen, die den Homocysteinspiegel zu senken vermögen - Google Patents
Kombination von blutdrucksenkenden Wirkstoffen mit Wirkstoffen, die den Homocysteinspiegel zu senken vermögenInfo
- Publication number
- DE10004651A1 DE10004651A1 DE10004651A DE10004651A DE10004651A1 DE 10004651 A1 DE10004651 A1 DE 10004651A1 DE 10004651 A DE10004651 A DE 10004651A DE 10004651 A DE10004651 A DE 10004651A DE 10004651 A1 DE10004651 A1 DE 10004651A1
- Authority
- DE
- Germany
- Prior art keywords
- combination
- acid
- agents
- nicotinic acid
- diuretics
- 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.)
- Ceased
Links
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 title claims abstract description 9
- 239000003814 drug Substances 0.000 title claims abstract 4
- 239000002220 antihypertensive agent Substances 0.000 title claims description 15
- 229940079593 drug Drugs 0.000 title claims 2
- 229940030600 antihypertensive agent Drugs 0.000 title description 10
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims abstract description 19
- 208000033892 Hyperhomocysteinemia Diseases 0.000 claims abstract description 14
- -1 cyano- Chemical class 0.000 claims abstract description 14
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims abstract description 12
- 235000019152 folic acid Nutrition 0.000 claims abstract description 12
- 239000011724 folic acid Substances 0.000 claims abstract description 12
- 229960000304 folic acid Drugs 0.000 claims abstract description 12
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000005541 ACE inhibitor Substances 0.000 claims abstract description 9
- 229940127291 Calcium channel antagonist Drugs 0.000 claims abstract description 9
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims abstract description 9
- 239000002934 diuretic Substances 0.000 claims abstract description 9
- 229940030606 diuretics Drugs 0.000 claims abstract description 9
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims abstract description 8
- 229960004308 acetylcysteine Drugs 0.000 claims abstract description 8
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims abstract description 8
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims abstract description 8
- LXNHXLLTXMVWPM-UHFFFAOYSA-N Vitamin B6 Natural products CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims abstract description 6
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000011726 vitamin B6 Substances 0.000 claims abstract description 6
- 235000019158 vitamin B6 Nutrition 0.000 claims abstract description 6
- 229940011671 vitamin b6 Drugs 0.000 claims abstract description 6
- TZBGSHAFWLGWBO-ABLWVSNPSA-N (2s)-2-[[4-[(2-amino-4-oxo-5,6,7,8-tetrahydro-1h-pteridin-6-yl)methylamino]benzoyl]amino]-5-methoxy-5-oxopentanoic acid Chemical compound C1=CC(C(=O)N[C@@H](CCC(=O)OC)C(O)=O)=CC=C1NCC1NC(C(=O)NC(N)=N2)=C2NC1 TZBGSHAFWLGWBO-ABLWVSNPSA-N 0.000 claims abstract description 5
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 claims abstract description 5
- MPJKWIXIYCLVCU-UHFFFAOYSA-N Folinic acid Natural products NC1=NC2=C(N(C=O)C(CNc3ccc(cc3)C(=O)NC(CCC(=O)O)CC(=O)O)CN2)C(=O)N1 MPJKWIXIYCLVCU-UHFFFAOYSA-N 0.000 claims abstract description 5
- 206010020772 Hypertension Diseases 0.000 claims abstract description 5
- 235000008191 folinic acid Nutrition 0.000 claims abstract description 5
- 239000011672 folinic acid Substances 0.000 claims abstract description 5
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 claims abstract description 5
- 229960001691 leucovorin Drugs 0.000 claims abstract description 5
- 230000003225 hyperhomocysteinemia Effects 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 claims description 7
- 229960003237 betaine Drugs 0.000 claims description 7
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
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- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 abstract 8
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- 239000011664 nicotinic acid Substances 0.000 abstract 4
- PFWLFWPASULGAN-UHFFFAOYSA-N 7-methylxanthine Chemical compound N1C(=O)NC(=O)C2=C1N=CN2C PFWLFWPASULGAN-UHFFFAOYSA-N 0.000 abstract 2
- 229940123208 Biguanide Drugs 0.000 abstract 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 abstract 2
- 229940035676 analgesics Drugs 0.000 abstract 2
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- 150000002632 lipids Chemical class 0.000 abstract 2
- 229910052744 lithium Inorganic materials 0.000 abstract 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 abstract 2
- 229960003105 metformin Drugs 0.000 abstract 2
- 230000003637 steroidlike Effects 0.000 abstract 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 abstract 2
- 229960000278 theophylline Drugs 0.000 abstract 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 abstract 1
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- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 abstract 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 abstract 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 abstract 1
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- 229960002582 perindopril Drugs 0.000 description 1
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
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- 229920000046 polythiazide Polymers 0.000 description 1
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- JTZQCHFUGHIPDF-RYVBEKKQSA-M potassium canrenoate Chemical compound [K+].O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)CCC([O-])=O)[C@@H]4[C@@H]3C=CC2=C1 JTZQCHFUGHIPDF-RYVBEKKQSA-M 0.000 description 1
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- 230000002265 prevention Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
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- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Es ist eine neue Beobachtung, dass eine Hyperhomocysteinämie durch die Einnahme von
Diuretika, Calciumantagonisten, ACE-Hemmern oder Angiotensin-II Rezeptorantagonisten
entsteht. Diese Wirkstoffe oder Kombinationen dieser Wirkstoffe werden zur Therapie von
Bluthochdruck eingesetzt. Die Entwicklung einer Hyperhomocysteinämie stellt eine bisher nicht
bekannte Nebenwirkung dieser Wirkstoffe dar. Diese Nebenwirkung ist eine neu beobachtete
Nebenwirkung, die bei Einnahme der blutdrucksenkenden Wirkstoffe regelmäßig und häufig
auftrat. Die biochemische Ursache dieser Hyperhomocysteinämie ist nicht bekannt.
Erhöhte Homocysteinspiegel stellen einen Risikofaktor für die Entstehung der koronaren
Herzkrankheit, des Apoplex sowie der peripheren Verschlusskrankheit dar. Eine Behandlung
dieser erhöhten Homocysteinspiegel wird daher im Rahmen der Prävention der koronaren
Herzkrankheit, des Apoplexes und der peripheren Verschlusskrankheit durchgeführt. Es sind
angeborene und erworbene Ursachen der Hyperhomocysteinämie (erhöhte Spiegel der
Aminosäure Homocystein im Blutplasma) bekannt. Mangelzustände der Vitamine Cobalamin,
Folsäure oder Vitamin B6 stellen eine häufige Ursache einer Hyperhomocysteinämie dar. Zur
Behandlung der Hyperhomocysteinämie ist die Verwendung einzelner oder mehrerer folgender
Wirkstoffe bereits bekannt: Cobalamin (Cyano-, Hydroxo-, Methyl-), Folsäure
(Pteroylglutaminsäure, Methyltetrahydrofolat, Folinsäure), Vitamin B6 (Pyridoxinchlorid), Betain
und N-Acetylcystein.
Der vorliegenden Erfindung liegt die Aufgabe zugrunde, die Entstehung einer durch
blutdrucksenkende Wirkstoffe wie Diuretika, Calciumantagonisten, ACE-Hemmern oder
Angiotensin-II Rezeptorantagonisten oder deren Abkömmlinge induzierte Hyperhomocysteinämie
mittels geeigneter Wirkstoffgaben zu verhindern.
Es wurde gefunden, und darin liegt die Lösung der Aufgabe, dass eine Kombination aus einem
oder mehreren blutdrucksenkenden Wirkstoffen wie Diuretika, Calciumantagonisten, ACE-
Hemmer oder Angiotensin-II Rezeptorantagonisten oder deren Abkömmlinge mit einem oder
mehreren der folgenden Wirkstoffe: Cobalamin (Cyano-, Hydroxo-, Methyl-), Folsäure
(Pteroylglutaminsäure, Methyltetrahydrofolat, Folinsäure), Vitamin B6 (Pyridoxinchlorid), Betain
und N-Acetylcystein, geeignet ist, einen Anstieg der Homocysteinkonzentration im Blutplasma,
wie sie bei Gabe eines oder mehrerer oder einer Kombination der blutdrucksenkenden Wirkstoffe
beobachtet wurde, verhindern kann.
Es war erstaunlich und nicht vorhersehbar, dass sich durch einen oder die Kombination von
mehreren dieser blutdrucksenkenden Wirkstoffe mit den Vitaminen eine Senkung der
Homocysteinwerte erreichen ließ, da durch die Einnahme der blutdrucksenkenden Wirkstoffe kein
Vitaminmangel erzeugt wurde.
Die Verwendung von Diuretika, Calciumantagonisten, ACE-Hemmern, und Angiotensin-II
Rezeptorantagonisten in pharmazeutischen Zubereitungen zur Therapie und Prophylaxe des
Bluthochdrucks ist bereits bekannt. Wirkstoffe, die zur Stoffklasse der Diuretika,
Calciumantagonisten, ACE-Hemmer oder Angiotensin-II Rezeptorantagonisten zählen, sind in
Tabelle 1 aufgeführt. Es sind bereits andere Nebenwirkungen als die neu gefundene
Hyperhomocysteinämie bei der Einnahme dieser blutdrucksenkenden Wirkstoffe bekannt.
Die Eignung der Wirkstoffkombination zur Behandlung der durch die Gabe eines oder mehrerer
oder einer Kombination der blutdrucksenkenden Wirkstoffe induzierten Hyperhomocysteinämie
lässt sich in üblichen klinischen Studien darstellen. Bei der angegebenen Indikation sollen die
homocysteinsenkenden Wirkstoffe in folgenden Tagesdosierungen eingesetzt werden:
| Cobalamin | bis 10000 µg |
| Folsäure | bis 15 mg |
| Pyridoxin | bis 500 mg |
| Betain | bis 20 g |
| N-Acetylcystein | bis 5000 mg |
Die Kombination der blutdrucksenkenden Wirkstoffe mit den genannten Vitaminen kann
vorzugsweise peroral, z. B. in Form von Dragees oder Filmtabletten, verabreicht werden. Die
Kombination der blutdrucksenkenden Wirkstoffe mit Betain oder N-Acetylcystein kann
vorzugsweise peroral, z. B. in Form einer Brausetablette verabreicht werden.
Die folgenden Beispiele dienen dazu, die Erfindung zu beschreiben, ohne dass es beabsichtigt ist,
die Erfindung auf diese Beispiele zu beschränken.
| Dragee | |
| Hydrochlorothiazid | 25 mg |
| Cyanocobalamin | 1000 µg |
| Pteroylglutaminsäure | 100 µg |
| Pyridoxinchlorid | 2 mg |
| AL=L<Hilfs- und Füllstoffe |
| Gelatinekapsel | |
| Furosemid | 20 mg |
| Betain | 2 g |
| AL=L<Hilfs- und Füllstoffe |
| Brausetablette | |
| Amilorid | 2,5 mg |
| Trichlormethiazid | 2 mg |
| N-Acetylcystein | 600 mg |
| Filmtablette | |
| Captopril | 25 mg |
| Cyanocobalamin | 1000 µg |
| Pteroylglutaminsäure | 100 µg |
| AL=L<Hilfs- und Füllstoffe |
| Filmtablette | |
| Losartan | 50 mg |
| Cyanocobalamin | 1000 µg |
| Pteroylglutaminsäure | 100 µg |
| AL=L<Hilfs- und Füllstoffe |
Captopril
Enalapril
Lisinopril
Perindopril
Ramipril
Quinapril
Benazepril
Cilazapril
Fosinopril
Trandolapril
Spirapril
Delapril
Moexipril
Enalapril
Lisinopril
Perindopril
Ramipril
Quinapril
Benazepril
Cilazapril
Fosinopril
Trandolapril
Spirapril
Delapril
Moexipril
Losartan
Eprosartan
Valsartan
Irbesartan
Tasosartan
Candesartan
Eprosartan
Valsartan
Irbesartan
Tasosartan
Candesartan
Bendroflumethiazid
Hydroflumethiazid
Hydrochlorothiazid
Chlorothiazid
Polythiazid
Trichlormethiazid
Methyclothiazid
Cyclothiazid
Mebutizid
Butizid
Bemetizid
Hydroflumethiazid
Hydrochlorothiazid
Chlorothiazid
Polythiazid
Trichlormethiazid
Methyclothiazid
Cyclothiazid
Mebutizid
Butizid
Bemetizid
Qineathazon
Clopamid
Chlortalidon
Mefrusid
Clofenamid
Metolazon
Xipamid
Indapamid
Fenquizon
Cicletanin
Clopamid
Chlortalidon
Mefrusid
Clofenamid
Metolazon
Xipamid
Indapamid
Fenquizon
Cicletanin
Furosemid
Bumetanid
Piretanid
Torasemid
Azosemit
Etacrynsäure
Etozolin
Spironolacton
Kaliumcanrenoat
Canrenon
Bumetanid
Piretanid
Torasemid
Azosemit
Etacrynsäure
Etozolin
Spironolacton
Kaliumcanrenoat
Canrenon
Amilorid
Triamteren
Triamteren
Nifedipin
Nicardipin
Nisoldipin
Nilvadipin
Isradipin
Felodipin
Nimodipin
Nitrendipin
Amlodipin
Verapamil
Gallopamil
Mibefradil
Diltiazem
Flunarizin
Fendilin
Flunarizin
Nicardipin
Nisoldipin
Nilvadipin
Isradipin
Felodipin
Nimodipin
Nitrendipin
Amlodipin
Verapamil
Gallopamil
Mibefradil
Diltiazem
Flunarizin
Fendilin
Flunarizin
Claims (3)
1. Herstellung von Kombinationsparäparaten zur Therapie einer Hyperhomocysteinämie bei
Bluthochdruck, die blutdrucksenkende Wirkstoffe und homocysteinsenkende Wirkstoffe
enthalten. Die blutdrucksenkenden Wirkstoffe sind Diuretika, Calciumantagonisten, ACE-
Hemmer oder Angiotensin-II Rezeptorantagonisten oder deren Abkömmlinge allein oder in
Kombination miteinander. Die homocysteinsenkenden Wirkstoffe sind Cobalamin (Cyano-,
Hydroxo-, Methyl-), Folsäure (Pteroylglutaminsäure, Methyltetrahydrofolat, Folinsäure), Vitamin
B6 (Pyridoxinchlorid), Betain und N-Acetylcystein allein oder in Kombination miteinander.
2. Verwendung von Kombinationspräparaten, die blutdrucksenkende Wirkstoffe und
homocysteinsenkende Wirkstoffe enthalten, zur Therapie einer durch blutdrucksenkende
Wirkstoffe induzierten Hyperhomocysteinämie. Die blutdrucksenkenden Wirkstoffe sind
Diuretika, Calciumantagonisten, ACE-Hemmer oder Angiotensin-II Rezeptorantagonisten oder
deren Abkömmlinge allein oder in Kombination miteinander. Die homocysteinsenkenden
Wirkstoffe sind Cobalamin (Cyano-, Hydroxo-, Methyl-), Folsäure (Pteroylglutaminsäure,
Methyltetrahydrofolat, Folinsäure), Vitamin B6 (Pyridoxinchlorid), Betain und N-Acetylcystein
allein oder in Kombination miteinander.
3. Verwendung eines Kombinationspräparates nach Anspruch 2 zur Behandlung einer
Hyperhomocysteinämie bei der Therapie von Bluthochdruck.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10004651A DE10004651A1 (de) | 2000-02-03 | 2000-02-03 | Kombination von blutdrucksenkenden Wirkstoffen mit Wirkstoffen, die den Homocysteinspiegel zu senken vermögen |
| PCT/EP2000/008801 WO2001056609A1 (de) | 2000-02-03 | 2000-09-08 | Pharmazeutische zusammensetzung für die behandlung einer durch arzneimittel induzierten hyperhomocysteinämie |
| AU2000272858A AU2000272858A1 (en) | 2000-02-03 | 2000-09-08 | Pharmaceutical composition for treating hyperhomocysteinaemia caused by medicaments |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10004651A DE10004651A1 (de) | 2000-02-03 | 2000-02-03 | Kombination von blutdrucksenkenden Wirkstoffen mit Wirkstoffen, die den Homocysteinspiegel zu senken vermögen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE10004651A1 true DE10004651A1 (de) | 2001-08-16 |
Family
ID=7629642
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE10004651A Ceased DE10004651A1 (de) | 2000-02-03 | 2000-02-03 | Kombination von blutdrucksenkenden Wirkstoffen mit Wirkstoffen, die den Homocysteinspiegel zu senken vermögen |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU2000272858A1 (de) |
| DE (1) | DE10004651A1 (de) |
| WO (1) | WO2001056609A1 (de) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003097045A1 (en) * | 2002-05-17 | 2003-11-27 | Novartis Ag | Combination of organic compounds |
| US10016379B2 (en) | 2015-10-30 | 2018-07-10 | Robin L. Webb | Method of treatment for third spacing |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7608640B2 (en) | 1999-03-02 | 2009-10-27 | Jallal Messadek | Glycine betaine and its use |
| AU2002350432A1 (en) * | 2001-11-26 | 2003-06-10 | Astion Oncology Aps | Combination of cimetidine and cysteine derivatives for treating cancer |
| BE1015608A6 (fr) | 2003-07-15 | 2005-06-07 | Messadek Jallal | Traitement des arterites. |
| CA2534660A1 (en) * | 2003-08-05 | 2005-02-10 | Galephar M/F | Single unit pharmaceutical composition comprising a mixture of a fibrate and an homocysteine reducing agent |
| IL157397A (en) * | 2003-08-14 | 2013-03-24 | Dpharm Ltd | Compounds, pharmaceutical compositions comprising same and uses thereof for the preparation of a medicament for the treatment of epilepsy |
| ITRM20030442A1 (it) * | 2003-09-26 | 2005-03-27 | Medosan Ind Biochimiche Riuni Te S R L | Composizione farmaceutica (stressen) per il trattamento di iperomocisteinemia. |
| CA2572815A1 (en) * | 2004-07-09 | 2006-01-19 | Medicure International Inc. | Combination therapies employing nicotinic acid derivatives or fibric acid derivatives |
| WO2006050581A2 (en) | 2004-11-10 | 2006-05-18 | Jallal Messadek | Betaine as agent against arthropod - or mosquito -borne diseases |
| EP1681055A1 (de) * | 2005-01-13 | 2006-07-19 | PEJO Iserlohn Heilmittel-und Diät-GmbH & Co.KG | Pharmazeutische Zubereitung zur Behandlung eines erhöhten Homocysteinspiegels |
| WO2006086856A1 (en) * | 2005-02-15 | 2006-08-24 | Messadek, Jallal | Combination therapeutic compositions and method of use |
| MX2007013486A (es) | 2005-04-27 | 2008-03-14 | Jallal Messadek | Combinaciones de insulinas. |
| CN100497337C (zh) | 2006-11-20 | 2009-06-10 | 淮北辉克药业有限公司 | 叶酸二甲双胍及其制备方法 |
| CN103386130A (zh) * | 2013-06-27 | 2013-11-13 | 深圳奥萨医药有限公司 | Ace抑制剂/噻嗪类利尿剂/5-甲基四氢叶酸药物组合物及用途 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998019690A1 (en) * | 1996-11-06 | 1998-05-14 | Bristol-Myers Squibb Company | Method for treating alzheimer's disease |
| WO1999044563A2 (en) * | 1998-03-06 | 1999-09-10 | Brown Charles L Iii | Composition for treatment and prevention of coronary artery disease |
-
2000
- 2000-02-03 DE DE10004651A patent/DE10004651A1/de not_active Ceased
- 2000-09-08 WO PCT/EP2000/008801 patent/WO2001056609A1/de active Application Filing
- 2000-09-08 AU AU2000272858A patent/AU2000272858A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998019690A1 (en) * | 1996-11-06 | 1998-05-14 | Bristol-Myers Squibb Company | Method for treating alzheimer's disease |
| WO1999044563A2 (en) * | 1998-03-06 | 1999-09-10 | Brown Charles L Iii | Composition for treatment and prevention of coronary artery disease |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003097045A1 (en) * | 2002-05-17 | 2003-11-27 | Novartis Ag | Combination of organic compounds |
| US8101599B2 (en) | 2002-05-17 | 2012-01-24 | Novartis Ag | Pharmaceutical composition containing anti-hypertensive agents |
| US10016379B2 (en) | 2015-10-30 | 2018-07-10 | Robin L. Webb | Method of treatment for third spacing |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2000272858A1 (en) | 2001-08-14 |
| WO2001056609A1 (de) | 2001-08-09 |
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