DK160034B - PHARMACEUTICAL PREPARATION, PARTICULARLY FOR TREATMENT OF CARDIOVASCULAR DISORDERS - Google Patents
PHARMACEUTICAL PREPARATION, PARTICULARLY FOR TREATMENT OF CARDIOVASCULAR DISORDERS Download PDFInfo
- Publication number
- DK160034B DK160034B DK416185A DK416185A DK160034B DK 160034 B DK160034 B DK 160034B DK 416185 A DK416185 A DK 416185A DK 416185 A DK416185 A DK 416185A DK 160034 B DK160034 B DK 160034B
- Authority
- DK
- Denmark
- Prior art keywords
- alfuzosin
- diltiazem
- treatment
- blood pressure
- pharmaceutical preparation
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (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)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Description
DK 160034BDK 160034B
iin
Den foreliggende opfindelse angår et farmaceutisk præparat især til behandling af cardiovasculære lidelser og urinblærelidelser, såsom hyperaktiv urinblære. Det farmaceutiske præparat ifølge opfindelsen indeholder alfuzosin 5 og diltiazem, som er anvendelige ved behandling af car diovasculære lidelser, især af hypertension af en hvilken som helst oprindelse, samt af angina pectoris.The present invention relates to a pharmaceutical composition in particular for the treatment of cardiovascular disorders and urinary bladder disorders such as hyperactive urinary bladder. The pharmaceutical composition of the invention contains alfuzosin 5 and diltiazem which are useful in the treatment of car diovascular disorders, especially of hypertension of any origin, and of angina pectoris.
Diltiazem med formlen: /0CH3Diltiazem of the formula: / OCH3
OISLAND
/ 0 0 ™r\ CH3 er kendt for sin virkning mod angina pectoris og sin 10 antihypertensive virkning./ 0 0 ™ r \ CH3 is known for its action against angina pectoris and its antihypertensive effect.
Alfuzosin med formlen: ch3 ch3oAJU« nh2 udviser ligeledes antihypertensiv virkning.Alfuzosin of the formula: ch3 ch3oAJU «nh2 also exhibits antihypertensive effect.
DK 16 O O 3 4 BDK 16 O O 3 4 B
22
Man har nu overraskende fundet, at der opnås en syner-gistisk antihypertensiv virkning når de to forbindelser kombineres. Den foreliggende opfindelse angår således et farmaceutisk præparat, som er ejendommeligt ved, 5 at det indeholder diltiazem og alfuzosin.It has now surprisingly been found that a synergistic antihypertensive effect is obtained when the two compounds are combined. The present invention thus relates to a pharmaceutical composition which is characterized in that it contains diltiazem and alfuzosin.
De farmaceutiske præparater ifølge den foreliggende opfindelse er blevet underkastet en serie af farmakologiske undersøgelser, som påviser deres værdifulde egenskaber indenfor det cardiovasculære område.The pharmaceutical compositions of the present invention have been subjected to a series of pharmacological studies demonstrating their valuable properties in the cardiovascular field.
10 Man har anvendt følgende afprøvningsmetoder: 1. Intravenøs afprøvning10 The following test methods have been used: 1. Intravenous testing
Man anæstetiserede SHR rotter med en alder over 5 måneder med natriumpentobarbital (60 mg/kg i.v.), og man forberedte dem således, at blodtrykket måles fra en kanyle 15 anlagt i carotidarterien.SHR rats were anesthetized with sodium pentobarbital (60 mg / kg i.v.) over 5 months of age and prepared to measure blood pressure from a cannula placed in the carotid artery.
De forbindelser, som skulle afprøves, blev indgivet intravenøst gennem femoralvenen.The compounds to be tested were administered intravenously through the femoral vein.
Man infunderede ad denne intravenøse vej lO^ug/kg/min. diltiazem eller det tilsvarende opløsningsmiddel i 45 20 minutter (opløsningsmidlet er destilleret vand inde holdende 0,9¾ NaCl).This intravenous route was infused 10 µg / kg / min. diltiazem or the corresponding solvent for 45 minutes (the solvent is distilled water containing 0.9¾ NaCl).
10 minutter senere indsprøjtede man alfuzosin (2^ug/kg/minά 5 minutter). Man målte de maksimale ændringer i blodtrykket efter indsprøjtningen af diltiazem, af alfuzosin 25 eller af de to kombineret.Ten minutes later, alfuzosin (2 µg / kg / min for 5 minutes) was injected. Maximum changes in blood pressure were measured after diltiazem injection, alfuzosin 25 or the two combined.
Diltiazem alene fremkalder en vedvarende sænkning af blodtrykket på 12,6 + 2,1 mm Hg (n=15).Diltiazem alone induces a sustained decrease in blood pressure of 12.6 + 2.1 mm Hg (n = 15).
DK 160034 BDK 160034 B
33
Under anvendelse af alfuzosin alene er sænkningen af blodtrykket på 19,7 + 4,7 mm Hg (n=6) efter afslutning af indgiften, og på 4,2 + 1,5 mm Hg 15 minutter senere.Using alfuzosin alone, the blood pressure decrease was 19.7 + 4.7 mm Hg (n = 6) after the end of administration, and 4.2 + 1.5 mm Hg 15 minutes later.
5 Med kombinationen diltiazem/alfuzosin er sænkningen af blodtrykket 58,4 + 7,8 mm Hg (n=7) ved afslutningen af tilførslen af alfuzosin, og den er stadig 15 minutter senere 48,7 + 8,7 mm Hg.With the diltiazem / alfuzosin combination, the lowering of blood pressure is 58.4 + 7.8 mm Hg (n = 7) at the end of the infusion of alfuzosin, and it is still 48.7 + 8.7 mm Hg 15 minutes later.
10 2. Afprøvning pr. os10 2. Testing per. U.S
Ved denne afprøvning pr. os anvendte man SHR han rotter i vågen tilstand, som havde en alder på mere end 5 måneder .In this test per. we used SHR he rats in wakefulness, who had an age of more than 5 months.
1515
Man målte kontinuert arterieblodtrykket og hjertets frekvens ud fra en arterie i halen, som var forsynet med en kanyle. Efter at arterieblodtrykket var stabiliseret (efter ca. 2 timer), modtog dyrene med peroral ind-20 gift i et rumfang på 5 ml/kg, enten 1 mg/kg alfuzosin, eller 12,5 mg/kg diltiazem, eller placebo (destilleret vand + 0,2¾ "Tween 80") eller også kombinationen diltiazem/ alfuzosin.Continuous arterial blood pressure and heart rate were measured from an artery fitted with a cannula. After arterial blood pressure stabilized (after about 2 hours), the animals received oral administration at a volume of 5 ml / kg, either 1 mg / kg alfuzosin, or 12.5 mg / kg diltiazem, or placebo (distilled water + 0.2¾ "Tween 80") or also the diltiazem / alfuzosin combination.
25 Den perorale indgift af 12,5 mg/kg diltiazem havde ikke nogen signifikant indflydelse på arterieblodtrykket eller på hjertets frekvens hos rotterne.The oral administration of 12.5 mg / kg diltiazem had no significant effect on arterial blood pressure or heart rate in the rats.
Alfuzosin (1 mg/kg p.o.) nedsætter i ringe udstrækning 30 arterieblodtrykket (-22 + 4 mm Hg efter 30 minutters forløb, idet det oprindelige blodtryk var 186 + 4 mm Hg; n = 9). 1 time efter behandlingen er denne parameter vendt tilbage til sin oprindelige værdi.Alfuzosin (1 mg / kg p.o.) to a minor extent decreases arterial blood pressure (-22 + 4 mm Hg after 30 minutes, the original blood pressure being 186 + 4 mm Hg; n = 9). 1 hour after treatment, this parameter has returned to its original value.
35 Kombinationen alfuzosin/diltiazem fremkalder en sænkning af arterieblodtrykket.The combination alfuzosin / diltiazem causes a decrease in arterial blood pressure.
DK 160034 BDK 160034 B
44
Den hypotensive aktivitet af denne kombination er maksimal 15 minutter efter behandling (-96 + 4 mm Hg; det oprindelige tryk = 195 + 5 mm Hg; n = 11).The hypotensive activity of this combination is maximal 15 minutes after treatment (-96 + 4 mm Hg; initial pressure = 195 + 5 mm Hg; n = 11).
5 1 time efter behandlingen er sænkningen stadig lig med 70¾ af den maksimale værdi.5 1 hour after treatment, the reduction is still equal to 70¾ of the maximum value.
4 timer efter behandlingen er sænkningen stadig svarende til 30¾ af den maksimale værdi.4 hours after treatment, the reduction is still equivalent to 30¾ of the maximum value.
1010
Hjertets frekvens ændres ikke signifikant hverken af de enkelte forbindelser eller ved kombinationen deraf.The heart rate is not significantly altered either by the individual compounds or by the combination thereof.
15 De ovenfor beskrevne resultater viser, at der foreligger en synergisme mellem de antihypertensive virkninger af diltiazem og af alfuzosin.The results described above show that there is a synergism between the antihypertensive effects of diltiazem and of alfuzosin.
De farmaceutiske forbindelser ifølge den foreliggende 20 opfindelse kan indeholde pr. doseringsenhed fra 25 til 160 mg diltiazem og fra 0,1 - 10 mg alfuzosin.The pharmaceutical compounds of the present invention may contain per dosage unit from 25 to 160 mg of diltiazem and from 0.1 to 10 mg of alfuzosin.
De kan foreligge i en hvilken som helst egnet form til peroral eller til parenteral indgift i kombination med 25 en hvilken som helst egnet excipiens.They may be in any suitable form for oral or parenteral administration in combination with any suitable excipient.
Den daglige dosering er af en sådan størrelse, at man indgiver fra 25 til 320 mg diltiazem og fra 0,2 til 20 mg alfuzosin.The daily dosage is such that administration of 25 to 320 mg of diltiazem and 0.2 to 20 mg of alfuzosin is administered.
30 3530 35
Claims (2)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8414088A FR2570275B1 (en) | 1984-09-14 | 1984-09-14 | PHARMACEUTICAL COMPOSITIONS BASED ON DILTIAZEM AND ALFUSOZINE |
| FR8414088 | 1984-09-14 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK416185D0 DK416185D0 (en) | 1985-09-13 |
| DK416185A DK416185A (en) | 1986-03-15 |
| DK160034B true DK160034B (en) | 1991-01-21 |
| DK160034C DK160034C (en) | 1991-06-17 |
Family
ID=9307716
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK416185A DK160034C (en) | 1984-09-14 | 1985-09-13 | PHARMACEUTICAL PREPARATION, PARTICULARLY FOR TREATMENT OF CARDIOVASCULAR DISORDERS |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0178961B1 (en) |
| JP (1) | JPS6172718A (en) |
| AU (1) | AU574506B2 (en) |
| CA (1) | CA1256031A (en) |
| DE (1) | DE3579098D1 (en) |
| DK (1) | DK160034C (en) |
| FR (1) | FR2570275B1 (en) |
| HU (1) | HU193448B (en) |
| IL (1) | IL76377A (en) |
| NZ (1) | NZ213465A (en) |
| ZA (1) | ZA857057B (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2421888A1 (en) * | 1978-02-06 | 1979-11-02 | Synthelabo | ALKYLENE DIAMINE AMIDES AND THEIR APPLICATION IN THERAPEUTICS |
| JPS5970611A (en) * | 1982-10-15 | 1984-04-21 | Tanabe Seiyaku Co Ltd | Drug composition |
-
1984
- 1984-09-14 FR FR8414088A patent/FR2570275B1/en not_active Expired
-
1985
- 1985-01-14 JP JP60004810A patent/JPS6172718A/en not_active Expired - Lifetime
- 1985-09-06 EP EP85401730A patent/EP0178961B1/en not_active Expired - Lifetime
- 1985-09-06 DE DE8585401730T patent/DE3579098D1/en not_active Expired - Lifetime
- 1985-09-12 IL IL76377A patent/IL76377A/en not_active IP Right Cessation
- 1985-09-13 AU AU47430/85A patent/AU574506B2/en not_active Expired
- 1985-09-13 DK DK416185A patent/DK160034C/en not_active IP Right Cessation
- 1985-09-13 HU HU853463A patent/HU193448B/en unknown
- 1985-09-13 NZ NZ213465A patent/NZ213465A/en unknown
- 1985-09-13 ZA ZA857057A patent/ZA857057B/en unknown
- 1985-09-13 CA CA000490635A patent/CA1256031A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| EP0178961A1 (en) | 1986-04-23 |
| DE3579098D1 (en) | 1990-09-13 |
| FR2570275A1 (en) | 1986-03-21 |
| JPS6172718A (en) | 1986-04-14 |
| IL76377A (en) | 1989-12-15 |
| CA1256031A (en) | 1989-06-20 |
| DK416185A (en) | 1986-03-15 |
| AU574506B2 (en) | 1988-07-07 |
| AU4743085A (en) | 1986-04-24 |
| FR2570275B1 (en) | 1986-11-21 |
| DK160034C (en) | 1991-06-17 |
| DK416185D0 (en) | 1985-09-13 |
| EP0178961B1 (en) | 1990-08-08 |
| HU193448B (en) | 1987-10-28 |
| NZ213465A (en) | 1988-06-30 |
| HUT40569A (en) | 1987-01-28 |
| IL76377A0 (en) | 1986-01-31 |
| ZA857057B (en) | 1986-06-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | Antihypertensive and vasorelaxing activities of synthetic xanthone derivatives | |
| KR20010015807A (en) | Use of 9-deoxy-2',9-alpha-methano-3-oxa-4,5,6-trinor-3,7-(1',3'-interphenylene)-13,14-dihydro-prostaglandin f1 to treat peripheral vascular disease | |
| JP2006213736A (en) | Analgesic agent and use thereof | |
| KR100823668B1 (en) | Medicines for Treatment and Prevention of Neurogenic Pain | |
| KR100352425B1 (en) | Pharmaceutical compositions containing tetrahydroisoquinoline compounds | |
| Gilmore et al. | The effect of prostaglandin E2 in inducing sedation in the rat | |
| US4925837A (en) | Pharmaceutical compositions | |
| CZ285633B6 (en) | Use of indole derivatives for preparing medicaments | |
| DK160034B (en) | PHARMACEUTICAL PREPARATION, PARTICULARLY FOR TREATMENT OF CARDIOVASCULAR DISORDERS | |
| JPS59206309A (en) | Treatment of acute fit lesion and useful pharmaceutical composition | |
| AU2009307901A1 (en) | Method for treating pulmonary arterial hypertension | |
| FR2684381A1 (en) | COMPOUNDS HAVING A PHOSPHORIC AMIDE LINK OR AN ENOL PHOSPHATE LINK FOR THEIR APPLICATION AS A THERAPEUTICALLY ACTIVE SUBSTANCE. | |
| KR20240150426A (en) | Parenteral respiratory stimulant formulations | |
| EP0866701A1 (en) | Synergistic immunosuppressant composition containing a 2,2'-bi-1h-pyrrole compound | |
| CA2836655C (en) | Heparin-based compositions and methods for the inhibition of metastasis | |
| KR20240101622A (en) | Methods for treating respiratory depression controlled by non-opioids | |
| US12138267B2 (en) | Methods of treating respiratory depression modulated by a non-opioid agent | |
| Kato et al. | Antihypertensive Activity of Orally Administered Methyl O-(4-Hydroxy-3-Methoxycinnamoyl) Reserpate (CD-3400) in Conscious Hypertensive Rats | |
| Nattero et al. | Reserpine for migraine prophylaxis | |
| KR20240004887A (en) | High-conductivity potassium channel modulators, compositions thereof, methods of making the same, and methods of using the same | |
| Mao et al. | Ethanol microinjection into the area postrema selectively attenuates baroreflex sensitivity measured by vasopressin in conscious rats | |
| Wendt et al. | Long-term Treatment with Oxaprotiline in Patients with Endogenous Depression | |
| JPH06501468A (en) | Method | |
| Loegering et al. | The effect of noradrenaline infusions and adrenergic blocking agents on serum glutamic–oxalacetic transaminase in dogs | |
| Rosenfeld et al. | Pharmacologic effects of (2‐(2, 6‐dimethylphenoxy) propyl) trimethyl ammonium chloride hydrate in hypertensive patients |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUP | Patent expired |