SE506179C2 - Pharmaceutical low composition of benazepril and a thiazide diuretic - Google Patents

Pharmaceutical low composition of benazepril and a thiazide diuretic

Info

Publication number
SE506179C2
SE506179C2 SE9000050A SE9000050A SE506179C2 SE 506179 C2 SE506179 C2 SE 506179C2 SE 9000050 A SE9000050 A SE 9000050A SE 9000050 A SE9000050 A SE 9000050A SE 506179 C2 SE506179 C2 SE 506179C2
Authority
SE
Sweden
Prior art keywords
benazepril
hydrochlorothiazide
thiazide diuretic
dose
composition according
Prior art date
Application number
SE9000050A
Other languages
Swedish (sv)
Other versions
SE9000050L (en
Inventor
Armel Rosselet
Original Assignee
Ciba Geigy Ag
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Ciba Geigy Ag filed Critical Ciba Geigy Ag
Publication of SE9000050L publication Critical patent/SE9000050L/en
Publication of SE506179C2 publication Critical patent/SE506179C2/en

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
    • 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
    • A61P9/12—Antihypertensives

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

PURPOSE: To prepare a composition, comprising bezenapril or its salt and a thiazide diuretic agent and capable of treating a lesser degree to a medium degree of hypertension in a lower dose than that when used alone. CONSTITUTION: This composition comprises bezenapril in about 4-6mg, preferably about 5mg dose at a time or its pharmaceutically permissible salt and a thiazide diuretic agent in an amount of 80-120%, preferably 100% based on 1/8 of the minimal antihyopertensive initial dose recommended when used alone. Bendroflumethiazide, Chlorthalidone, Chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methylchlorothiazide, polythiazide, trichloromethiazide, benzthiazide and dichloroazide are cited as the thiazide diuretic agent. The most preferred composition comprises bezenapril hydrochloride and hydrochlorothiazide at about 0.8-1 weight ratio.

Description

soe 179 2' Det är en avsikt med föreliggande uppfinning att till- handahálla en farmaceutiskt kompositon för att behandla och en metod för behandling av mild till måttlig hypertension med en minimal mängd av aktivt medel, medan man uppnår tryckreduktio- ner icke uppnàbara med de individuella aktiva medlen vid samma dosering. It is an object of the present invention to provide a pharmaceutical composition for treating and a method for treating mild to moderate hypertension with a minimal amount of active agent, while achieving pressure reductions not achievable with the individual active agents at the same dosage.

Uppfinningen är ett fixerat förhållande av en lagdoskom- bination av 4-6 mg benazepril eller ett farmaceutiskt godtag- bart salt därav med 80-120 X av 1/8 av den antihypertensiva kliniskt rekommenderade dagliga begynnelsedosen av ett tiazid- diuretikum, som ges såsom en daglig engangsdosering. Föreligg- ande komposition är en daglig enhetsdos för administrering till en vuxen människa med mild till måttlig hypertension, vilken dos omfattar ca 4 till ca 6 mg, lämpligen ca 5 mg, ben- azepril-hydroklorid eller vilket annat farmaceutiskt godtag- bart salt av benazepril som helst och ca 80 % till ca 120 %, lämpligen ca 100 Z, av 1/8 av den vanliga antihypertensiva be- gynnelsedosen för vuxna av ett tiaziddiuretikum, när sàdant diuretikum användes ensamt.The invention is a fixed ratio of a low dose combination of 4-6 mg of benazepril or a pharmaceutically acceptable salt thereof with 80-120 X of 1/8 of the antihypertensive clinically recommended daily starting dose of a thiazide diuretic, given as a daily single dose. The present composition is a daily unit dose for administration to an adult of mild to moderate hypertension, which dose comprises about 4 to about 6 mg, preferably about 5 mg, benazepril hydrochloride or any other pharmaceutically acceptable salt of benazepril. at any time and about 80% to about 120%, preferably about 100 Z, of 1/8 of the usual initial dose for adults of a thiazide diuretic, when such a diuretic is used alone.

Farmaceutiskt godtagbara salter av benazepril är syraad- ditionssalter med farmakologiskt ofarliga syror, t ex med oor- ganisk syra, t ex saltsyra, svavelsyra eller fosforsyra, eller med organiska karbonsyror, sulfonsyror eller sulfosyror, t ex ättiksyra, propionsyra, glykolsyra, meleinsyra, fumarsyra, vinsyra, citronsyra, bensoesyra, metansulfonsyra, etansulfon- syra, eller 2-hydroxietansulfonsyra. Lämplig är hydrokloriden, d v s syraadditionssalter med saltsyra.Pharmaceutically acceptable salts of benazepril are acid addition salts with pharmacologically harmless acids, for example with organic acid, for example hydrochloric acid, sulfuric acid or phosphoric acid, or with organic carboxylic acids, sulphonic acids or sulpho acids, for example acetic acid, propionic acid, glycolic acid, glycolic acid , tartaric acid, citric acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, or 2-hydroxyethanesulfonic acid. The hydrochloride, i.e. acid addition salts with hydrochloric acid, are suitable.

Lämpligen utväljes diuretikum fran bendroflumetiazid (5 mg) 0,6-0,75 mg; klortalidon (25 mg) 2,5-3,75 mg; klortiazid (500 mg) 50-75 mg; hydroklortiazid (50 mg) 5-7,5 mg; hydroflumetiazid (50 mg) 5-7,5 mg; metylklortiazid (2,5 mg) 0,25-0,38 mg; polytiazid (2 mg) 0,2-0,3 mg; triklormetiazid (2 mg) 0,2-0,3 mg; benstiazid (50 mg) 0,5-0,75 mg; cyklotiazid (2 mg) 0,2-0,3 mg.Suitably the diuretic is selected from bendroflumethiazide (5 mg) 0.6-0.75 mg; chlorthalidone (25 mg) 2.5-3.75 mg; chlorothiazide (500 mg) 50-75 mg; hydrochlorothiazide (50 mg) 5-7.5 mg; hydroflumethiazide (50 mg) 5-7.5 mg; methyl chlorothiazide (2.5 mg) 0.25-0.38 mg; polythiazide (2 mg) 0.2-0.3 mg; trichloromethiazide (2 mg) 0.2-0.3 mg; benstiazide (50 mg) 0.5-0.75 mg; cyclothiazide (2 mg) 0.2-0.3 mg.

BNSDOCID: 40 BNSDOCID ö « . 506 179 Den vanliga kliniska antihypertensiva minimala begynnel- sedosen för vuxna visas inom parentes, följt av doseringppmrà- det, användbart i föreliggande uppfinning. Den kliniska pggyn- nelsedosen, som användes i vara dagar, kan skilja sig fran do- sen, som ges inom parentes i ovanstående lista i nagra fall.BNSDOCID: 40 BNSDOCID ö «. The usual clinical antihypertensive minimal initial dose for adults is shown in parentheses, followed by the dosage form useful in the present invention. The initial clinical dose used for days may differ from the dose given in parentheses in the list above in some cases.

Exempelvis ges ofta hydroklortiazid i en begynnelsedos !¥*' mg. @§;.For example, hydrochlorothiazide is often given in an initial dose of 1 mg. @ § ;.

Försträdesvis utväljes tiaziddiuretikum från klortiazid, hydroklortiazid, metylklortiazid och klortalidon. Lämpligast utväljes tiaziddiuretikum från klortiazid och hydroklortiazid; speciellt hydroklortiazid. p-.Preferably, thiazide diuretics are selected from chlorothiazide, hydrochlorothiazide, methylchlorothiazide and chlorthalidone. Most preferably, thiazide diuretic is selected from chlorothiazide and hydrochlorothiazide; especially hydrochlorothiazide. p-.

Den fördelaktigaste kompositionen omfattar benazepril- hydroklorid och hydroklortiazid i ett viktförhàllande av ca 0,8 till 1, t ex ca 5 mg benazepril-hydroklorid och ca §¿25 mg hydroklortiazid.The most advantageous composition comprises benazepril hydrochloride and hydrochlorothiazide in a weight ratio of about 0.8 to 1, eg about 5 mg of benazepril hydrochloride and about 25 mg of hydrochlorothiazide.

I ett kliniskt, och kvinnor med ett sittande diastoliskt blodtryck av 9§;¿$ mm slumpvis dubbelblindförsök med 334 man Hg jämfördes effekten av den lämpliga kombinationen enlig§_ uppfinningen, som omfattar 5 mg benazepril-hydroklorid och 8,25 mg hydroklortiazid, vilken komposition ges en gàng_s%gli- gen, med verkan av andra kompositioner och av de enstaka¿}Äke- medlen under sex veckor. Resultaten sammanfattas i följande tabell: sa~ mg benazaprila) + 6,25 mg hydroklortiazid - 9,9.mmHgb> 18 mg benazepril + 12,5 mg hydroklortiazid - 9¿§¿æp§g mg benazepril + 25 mg hydroklortiazid -13,§¶ëšBg mg benazepril - Q,8“æ§Hg mg hydroklortiazid - 6,9¿mHg mg benazepril + 6,25 mg hydroklortiazid -10,3 mmflg mg benazepril + 25 mg hydrokortiazidl -10,7 mHg blindprov - 3,9¿E¶Hg a) såsen hyaronorid ___, b) reduktion av sittande diastoliskt blodtryck ¿~w De kliniska resultatet visar att làgdoskompositionen en- ligt uppfinningen har en överraskande verkan. _ Kompositionen kan sättas tillsammans genom metodar¿_som är standard inom tekniken till varje lämplig doseringafogm in- _, 508179C2 I > 40 sus 179 4 klusive tablett, tiskt hjälpmedel eller bärare kan även innefattas. Administre- kapsel, pulver, etc. Varje lämpligt farmaceu- ring kan ske pà vilket sätt som helst genom vilket bàde ben- azepril och tiaziddiuretikum samtidigt kan administreras, men är mestadels lämpligen oral. Den lämpligaste doseringensformen är en fast, oral doseringsform, såsom en tablett eller kapsel.In a clinical, and women with a sitting diastolic blood pressure of 9; $ mm randomized double-blind trial of 334 man Hg, the effect of the appropriate combination according to the invention, comprising 5 mg of benazepril hydrochloride and 8.25 mg of hydrochlorothiazide, which composition is given once_s% gligen, with the effect of other compositions and of the individual¿} Remedies for six weeks. The results are summarized in the following table: sa ~ mg benazaprila) + 6.25 mg hydrochlorothiazide - 9.9.mmHgb> 18 mg benazepril + 12.5 mg hydrochlorothiazide - 9¿§¿æp§g mg benazepril + 25 mg hydrochlorothiazide -13, §¶ËšBg mg benazepril - Q, 8 “æ§Hg mg hydrochlorothiazide - 6.9¿mHg mg benazepril + 6.25 mg hydrochlorothiazide -10.3 mm fl g mg benazepril + 25 mg hydrocortiazidl -10.7 mHg blank - 3.9 ¿E¶Hg a) the sauce hyaronoride ___, b) reduction of sedentary diastolic blood pressure ¿~ w The clinical results show that the low-dose composition according to the invention has a surprising effect. The composition may be formulated by methods which are standard in the art for any suitable dosage form including a tablet, excipient or carrier may also be included. Administration capsule, powder, etc. Any suitable pharmacy can be by any means by which both benzepril and thiazide diuretic can be administered simultaneously, but are mostly suitably oral. The most suitable dosage form is a solid, oral dosage form, such as a tablet or capsule.

Medan andra antihypertensiva, aktiva medel kan tillsättas, är lämpligast endast benazepril och endast ett tiaziddiuretikum närvarande i en enda komposition.While other antihypertensive active agents may be added, most conveniently only benazepril and only one thiazide diuretic are present in a single composition.

Föreliggande uppfinning kommer mera fullständigt att förstås genom hänvisning till följande exempel, som belyser men icke begränsar uppfinningen.The present invention will be more fully understood by reference to the following examples, which illustrate but do not limit the invention.

Filmbelagda tabletter, som innehåller 6,25 mg 6-klor- Exempel: 3,4-dihydro-2H-1,2,4-bensotiadiazin-7-sulfonamid-1,1~dioxid och 5,00 mg 1-karboximetyl-35-(IS-etoxikarbonyl-3-fenylpropyl- amino)-2,3,4,5-tetrahydro-IH-I1Jbensazepin-2-on-hydroklorid framställes pà följande sätt: Bestàndsdelar (för 2 000 tabletter) Kärnmaterial 6-klor-3,4-dihydro-2H-1,2,4-bensotiadiazin-7-sulfon- amid-1,1-dioxid (mikroniserad) 12,50 g 1-karboximetyl-3S-(IS-etoxikarbonyl-3-fenylpropyl- amino)-2,3,4,5-tetrahydro-1H-E1]bensazepin-2-on- hydroklorid 10,00 g hydroxipropylmetylcellulosa 6,00 g hydrogenererad ricinolja 12,00 g laktos (malen) 423,50 g polyvinyl-polypyrrolidon 20,00 g Filmmaterial hydroxipropylmetylcellulosa 7,34 g polyvetylenglykol 8000 (flingor) 1,34 g talk - 5,32 g titandioxid 2,00 g 6-klor-3,4-dihydro-2H-1,2,4-bensotiadiazin-7-sulfonamid- 1,1-dioxid, 1-karboximetyl-35-(1S-etoxikarbonyl-3-fenylpropyl- amino)-2,3,4,5-tetrahydro~1H-E11bensazepin-2-on-hydroklorid BNSDOCID: och kärnan i hydroxipropyl-metylcellulosa blandas med en del av laktosen. återstående laktos tillsättes och blandningen granuleres med vatten, torkas och males. Återstàende kåšåëä- gredienser blandas därmed och den homogena blandningen ptässas till tabletter, som belägges med en vattenhaltig suspension av ovanstående belåggningsmeterial.Film-coated tablets containing 6.25 mg of 6-chloro- Example: 3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide and 5.00 mg of 1-carboxymethyl-35 - (1S-ethoxycarbonyl-3-phenylpropylamino) -2,3,4,5-tetrahydro-1H-1H-benzazepin-2-one hydrochloride is prepared as follows: Ingredients (for 2,000 tablets) Core material 6-chloro-3 , 4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide (micronized) 12.50 g of 1-carboxymethyl-3S- (1S-ethoxycarbonyl-3-phenylpropylamino) -2,3,4,5-tetrahydro-1H-E1] benzazepin-2-one hydrochloride 10.00 g hydroxypropyl methylcellulose 6.00 g hydrogenated castor oil 12.00 g lactose (ground) 423.50 g polyvinyl polypyrrolidone 20, 00 g Film material hydroxypropyl methylcellulose 7.34 g polyethylene glycol 8000 (flakes) 1.34 g talc - 5.32 g titanium dioxide 2.00 g 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7- sulfonamide-1,1-dioxide, 1-carboxymethyl-35- (1S-ethoxycarbonyl-3-phenylpropylamino) -2,3,4,5-tetrahydro-1H-E11benzazepin-2-one hydrochloride BNSDOCID: and the nucleus of hydroxypropyl- methylcellulose is mixed with part of the lactose. the remaining lactose is added and the mixture is granulated with water, dried and ground. The remaining cauliflower ingredients are mixed therewith and the homogeneous mixture is poured into tablets, which are coated with an aqueous suspension of the above coating material.

BNSDOCID BNSDOCID

Claims (11)

506 17.9 g 10 15 20 25 30 35 ?atontkrav506 17.9 g 10 15 20 25 30 35? Atontkrav 1. Farmaceutisk lägdoskomposition för behandling av mild till måttlig hypertension, k ä n n e t e c k n a d av ca 4 till ca 6 mg benazepril med formeln k o COOH COOCfl$3fi eller ett farmaceutiskt godtagbart salt av benazepril och ett tia- ziddiuretikum i en mängd från ca 80 % till 120 % av 1/8 av den minimala rekommenderade antihypertensiva begynnelsedosen av tiazid- diuretikum, när det användes ensamt, varvid varje mängd är per enhetsdos av kompositionen.A low dose pharmaceutical composition for the treatment of mild to moderate hypertension, characterized by about 4 to about 6 mg of benazepril of the formula ko COOH COOC fl $ 3fi or a pharmaceutically acceptable salt of benazepril and a thiazide diuretic in an amount of from about 80% to 120% of 1/8 of the minimum recommended initial antihypertensive dose of thiazide diuretic, when used alone, each amount being per unit dose of the composition. 2. komposition enligt krav 1, därav, att tiaziddiuretikum utväljes frän bendroflumetiazid, klorta- k ä n n e t e c k n a d lidon, klortiazid, hydroklortiazid, hydroflumetiazid, metylklortia- zid, polytiazid, triklormetiazid, benstiazid och cyklotiazid.A composition according to claim 1, wherein the thiazide diuretic is selected from bendroflumethiazide, chlorthacane n e t e c k n a d lidone, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methylchlorothiazide, polytiazide, trichloromethiazide, benzothiazide and cycstothiazide. 3. Komposition enligt krav 2, k ä n n e t e c k n a d därav, att tiaziddiuretikum är hydroklortiazid.3. A composition according to claim 2, characterized in that the thiazide diuretic is hydrochlorothiazide. 4. Komposition enligt krav 1, k ä n n e t e c k n a d därav, att tiaziddiuretikum är närvarande i en mängd, som är 1/B av den minimala rekomenderade antihypertensiva begynnelsedosen, när tiazi- diuretikum användes ensamt.Composition according to Claim 1, characterized in that the thiazide diuretic is present in an amount which is 1 / B of the minimum recommended initial antihypertensive dose, when the thiazide diuretic is used alone. 5. S. Komposition enligt krav 3, att hydroklortiazid är närvarande i en mängd från ca S mg till ca k ä n n e t e c k n a d därav, 7,5 mg per dos.5. The composition of claim 3, wherein the hydrochlorothiazide is present in an amount from about 5 mg to about 10 mg thereof, 7.5 mg per dose. 6. Komposition enligt krav 5, att hydroklortiazid är närvarande i en mängd av ca 6,25 mg per dos. k ä n n e t e c k n a d därav,The composition of claim 5, that hydrochlorothiazide is present in an amount of about 6.25 mg per dose. k ä n n e t e c k n a d thereof, 7. Komposition enligt krav 1, k â n n e t e c k n a d därav, att benazepril eller farmaceutiskt godtagbart salt därav är benazep- ril-hydroklorid.7. A composition according to claim 1, wherein benazepril or a pharmaceutically acceptable salt thereof is benazepril hydrochloride. 8. Komposition enligt krav 7, k ä n n e t e c k n a d därav, att benazepril-hydrklorid är närvarande i en mängd av ca 5 mg per dos.8. A composition according to claim 7, characterized in that benazepril hydrochloride is present in an amount of about 5 mg per dose. 9. Komposition enligt krav 1, k ä n n e t e c k n a d av S mg benazepril-hydroklorid och 6,25 mg hydroklortiazid per dos. BNSDOCID: 7 J 506 179Composition according to Claim 1, characterized by 5 mg of benazepril hydrochloride and 6.25 mg of hydrochlorothiazide per dose. BNSDOCID: 7 J 506 179 10. Komposition enligt krav 1, k à n n e t e c k n a'd därav, att den utgöres av en tablett, ett pulver eller en kapsel.10. A composition according to claim 1, characterized in that it consists of a tablet, a powder or a capsule. 11. Komosition enligt krav 1, k á n n e t e c k n a d därav, att den år en oral tablett eller oral kapsel. BNSDOCIDA composition according to claim 1, wherein it is an oral tablet or oral capsule. BNSDOCID
SE9000050A 1989-01-23 1990-01-08 Pharmaceutical low composition of benazepril and a thiazide diuretic SE506179C2 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US30038389A 1989-01-23 1989-01-23

Publications (2)

Publication Number Publication Date
SE9000050L SE9000050L (en) 1990-07-24
SE506179C2 true SE506179C2 (en) 1997-11-17

Family

ID=23158879

Family Applications (1)

Application Number Title Priority Date Filing Date
SE9000050A SE506179C2 (en) 1989-01-23 1990-01-08 Pharmaceutical low composition of benazepril and a thiazide diuretic

Country Status (24)

Country Link
JP (1) JP3009694B2 (en)
KR (1) KR0141479B1 (en)
AT (1) AT401728B (en)
AU (1) AU629288B2 (en)
BE (1) BE1002736A4 (en)
CA (1) CA2008126C (en)
CH (1) CH680568A5 (en)
CY (1) CY1835A (en)
DE (2) DE4001496C2 (en)
DK (1) DK175204B1 (en)
FR (1) FR2641971B1 (en)
GB (1) GB2227172B (en)
HK (1) HK98995A (en)
IE (1) IE61784B1 (en)
IL (1) IL93117A0 (en)
IT (1) IT1239744B (en)
LU (1) LU87660A1 (en)
MX (1) MX9203362A (en)
NL (1) NL194958C (en)
NZ (1) NZ232182A (en)
SA (1) SA90100151B1 (en)
SE (1) SE506179C2 (en)
SG (1) SG176194G (en)
ZA (1) ZA90429B (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100221695B1 (en) * 1991-08-12 1999-09-15 그린 마틴, 브라이언 쥐 테슬리 Pharmaceutical spheroid formulation
DK9200258U4 (en) * 1992-03-11 1993-07-23 Merck & Co Inc Pharmaceutical preparation containing enalapril for use in hypertension
GB9613470D0 (en) * 1996-06-27 1996-08-28 Ciba Geigy Ag Small solid oral dosage form
CN102579346B (en) * 2012-03-02 2013-09-25 海南美兰史克制药有限公司 Liposome solid preparation of benazepril/hydrochlorothiazide medicine combination

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4217347A (en) * 1977-12-27 1980-08-12 E. R. Squibb & Sons, Inc. Method of treating hypertension and medicaments therefor
IL58849A (en) * 1978-12-11 1983-03-31 Merck & Co Inc Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them
US4410520A (en) * 1981-11-09 1983-10-18 Ciba-Geigy Corporation 3-Amino-[1]-benzazepin-2-one-1-alkanoic acids
ZA833903B (en) * 1982-06-01 1984-11-28 Merck & Co Inc Benzofused lactams as antihypertensives
US4520021A (en) * 1982-07-02 1985-05-28 Merck & Co., Inc. Substituted caprolactam derivatives as antihypertensives

Also Published As

Publication number Publication date
AU629288B2 (en) 1992-10-01
IE900233L (en) 1990-07-23
DK17490A (en) 1990-07-24
IT1239744B (en) 1993-11-15
MX9203362A (en) 1992-07-01
CY1835A (en) 1995-12-01
IE61784B1 (en) 1994-11-30
DK175204B1 (en) 2004-07-12
KR900011465A (en) 1990-08-01
DE10199041I1 (en) 2002-01-10
SG176194G (en) 1995-05-12
IL93117A0 (en) 1990-11-05
AT401728B (en) 1996-11-25
NL194958C (en) 2003-09-02
HK98995A (en) 1995-06-30
BE1002736A4 (en) 1991-05-21
CA2008126A1 (en) 1990-07-23
DK17490D0 (en) 1990-01-22
JPH02233616A (en) 1990-09-17
GB2227172A (en) 1990-07-25
GB9001054D0 (en) 1990-03-14
FR2641971B1 (en) 1991-11-22
NZ232182A (en) 1991-06-25
ZA90429B (en) 1990-09-26
CH680568A5 (en) 1992-09-30
DE4001496A1 (en) 1990-07-26
FR2641971A1 (en) 1990-07-27
DE4001496C2 (en) 2001-05-10
GB2227172B (en) 1992-06-10
KR0141479B1 (en) 1998-06-01
IT9047548A1 (en) 1991-07-19
ATA13590A (en) 1996-04-15
AU4870390A (en) 1990-07-26
SE9000050L (en) 1990-07-24
JP3009694B2 (en) 2000-02-14
NL194958B (en) 2003-05-01
SA90100151B1 (en) 2006-10-02
IT9047548A0 (en) 1990-01-19
CA2008126C (en) 1999-11-09
NL9000158A (en) 1990-08-16
LU87660A1 (en) 1991-02-18

Similar Documents

Publication Publication Date Title
US4248857A (en) Sustained release pharmaceutical compositions
CA1147651A (en) Sustained release pharmaceutical compositions
AU613663B2 (en) Sustained release etodolac
EP1239831B1 (en) Improved pharmaceutical compositions for poorly soluble drugs
DE69732113T2 (en) QUICK-SOLUBLE TABLET CONTAINING GALANTHAMINE HYDROBROMIDE
CA1294877C (en) Anti-inflammatory cream composition
PL172571B1 (en) Controllable release morphine preparation
US4217347A (en) Method of treating hypertension and medicaments therefor
JP2003300907A (en) Antifungal preparation and the method for producing the same and use thereof
SE506179C2 (en) Pharmaceutical low composition of benazepril and a thiazide diuretic
US5853756A (en) Controlled release formulations of Ranitidine
JPH0840906A (en) Pharmaceutical preparation for curing hyperglycemia
TWI286072B (en) Sleeping medicine formed by coating solid
AU776242B2 (en) Riluzole and alpha-tocopherol combination
SE465751B (en) PHARMACEUTICAL PREPARATION CONTAINING CO-DERGOCRIN AND A CALCIUM ANTAGONIST
US4804540A (en) Process for preparing the combination products of triamterene and hydrochlorothiazide
KR960009649B1 (en) Pharmaceutical composition containing hydantoin derivatives
JPS61165327A (en) Remedy for hepatopathy
JPH05170741A (en) Thromboxane a2 antagonist
JPH03135917A (en) Uric acid evacuant
WO2001003701A1 (en) An oral composition having as a first active ingredient budesonide and as a second active ingredient an antibiotic, for use in intestinal conditions, especially crohn's disease
WO2001003703A1 (en) An oral composition having as a first active ingredient rofleponide and as a second active ingredient an antibiotic, for use in intestinal conditions, especially crohn's disease
CA2361581A1 (en) Method for the prevention or reduction of cariovascular events associated with coronary intervention
DE2456172A1 (en) CALCIUM MEDICINAL PRODUCT

Legal Events

Date Code Title Description
NUG Patent has lapsed