IE61784B1 - Low dose benazepril/thiazide diuretic composition - Google Patents
Low dose benazepril/thiazide diuretic compositionInfo
- Publication number
- IE61784B1 IE61784B1 IE23390A IE23390A IE61784B1 IE 61784 B1 IE61784 B1 IE 61784B1 IE 23390 A IE23390 A IE 23390A IE 23390 A IE23390 A IE 23390A IE 61784 B1 IE61784 B1 IE 61784B1
- Authority
- IE
- Ireland
- Prior art keywords
- composition according
- benazepril
- thiazide diuretic
- hydrochlorothiazide
- dose
- Prior art date
Links
- 239000003451 thiazide diuretic agent Substances 0.000 title claims abstract description 17
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 title claims abstract description 16
- 229960004530 benazepril Drugs 0.000 title claims abstract description 16
- 229940121792 Thiazide diuretic Drugs 0.000 title claims abstract description 13
- 239000000203 mixture Substances 0.000 title claims description 20
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229960002003 hydrochlorothiazide Drugs 0.000 claims abstract description 14
- 229960003619 benazepril hydrochloride Drugs 0.000 claims abstract description 9
- VPSRQEHTHIMDQM-FKLPMGAJSA-N benazepril hydrochloride Chemical compound Cl.C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 VPSRQEHTHIMDQM-FKLPMGAJSA-N 0.000 claims abstract description 9
- 229960002155 chlorothiazide Drugs 0.000 claims abstract description 5
- JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 claims abstract description 4
- CESYKOGBSMNBPD-UHFFFAOYSA-N Methyclothiazide Chemical compound ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CCl)NC2=C1 CESYKOGBSMNBPD-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229960001523 chlortalidone Drugs 0.000 claims abstract description 4
- CYLWJCABXYDINA-UHFFFAOYSA-N Polythiazide Polymers ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CSCC(F)(F)F)NC2=C1 CYLWJCABXYDINA-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229960001541 benzthiazide Drugs 0.000 claims abstract description 3
- NDTSRXAMMQDVSW-UHFFFAOYSA-N benzthiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1N=C2CSCC1=CC=CC=C1 NDTSRXAMMQDVSW-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229960003176 cyclothiazide Drugs 0.000 claims abstract description 3
- BOCUKUHCLICSIY-QJWLJZLASA-N cyclothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2C1[C@H](C=C2)C[C@H]2C1 BOCUKUHCLICSIY-QJWLJZLASA-N 0.000 claims abstract description 3
- 229960005483 polythiazide Drugs 0.000 claims abstract description 3
- 229920000046 polythiazide Polymers 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims description 7
- 230000003276 anti-hypertensive effect Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- -1 trichlormethiazidc Chemical compound 0.000 claims description 2
- 241000521257 Hydrops Species 0.000 claims 1
- 206010030113 Oedema Diseases 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 229940100691 oral capsule Drugs 0.000 claims 1
- 229940096978 oral tablet Drugs 0.000 claims 1
- 239000007935 oral tablet Substances 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 abstract description 5
- JBMKAUGHUNFTOL-UHFFFAOYSA-N Aldoclor Chemical class C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O JBMKAUGHUNFTOL-UHFFFAOYSA-N 0.000 abstract description 3
- 239000002552 dosage form Substances 0.000 abstract description 3
- 229960003515 bendroflumethiazide Drugs 0.000 abstract description 2
- HDWIHXWEUNVBIY-UHFFFAOYSA-N bendroflumethiazidum Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2CC1=CC=CC=C1 HDWIHXWEUNVBIY-UHFFFAOYSA-N 0.000 abstract description 2
- 229960003313 hydroflumethiazide Drugs 0.000 abstract description 2
- DMDGGSIALPNSEE-UHFFFAOYSA-N hydroflumethiazide Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O DMDGGSIALPNSEE-UHFFFAOYSA-N 0.000 abstract description 2
- 229960004813 trichlormethiazide Drugs 0.000 abstract description 2
- LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 abstract description 2
- 229940083085 thiazide derivative acting on arteriolar smooth muscle Drugs 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000005541 ACE inhibitor Substances 0.000 description 4
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 4
- 239000002934 diuretic Substances 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000011162 core material Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 2
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 2
- 229940097420 Diuretic Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000001882 diuretic effect Effects 0.000 description 2
- 229940030606 diuretics Drugs 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- QRAOZQGIUIDZQZ-UHFFFAOYSA-N 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1B1OC(C)(C)C(C)(C)O1 QRAOZQGIUIDZQZ-UHFFFAOYSA-N 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 239000004353 Polyethylene glycol 8000 Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940085678 polyethylene glycol 8000 Drugs 0.000 description 1
- 235000019446 polyethylene glycol 8000 Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
Abstract
A fixed ratio low dose combination of benazepril and a thiazide diuretic is useful for treating hypertension, particularly having about 4-6 mg of benazepril hydrochloride and about 5-7.5 mg of hydrochlorothiazide per dosage form. Suitable alternative thiazide derivatives are bendroflumethiazide, chlorthalidone, chlorothiazide, hydroflumethiazide, methylchlorothiazide, polythiazide, trichlormethiazide, benzthiazide and cyclothiazide.
Description
! - 1 - The invention relates to a pharmaceutical composition for treating mild to moderatehypertension containing the angiotensin converting enzyme inhibitor benazepril in combi-nation with thiazide diuretics, and to a method of treatment of hypertension utilizing thiscomposition. 5 Benazepril hydrochloride is a new orally active, non-sulfhydril containing, angiotensinconverting enzyme inhibitor having the structure The compound is described in U.S. 4,410,520. Thiazide diuretics, the second componentof the instant combination, have long been a mainstay of antihypertensive therapy. All ofthe active agents of the instant invention are well known compounds in the art; their syn-thesis, routes of administration, etc. are well known. Additionally, there has been someliterature published in recent years on combining angiotensin converting enzymeinhibitors with thiazide diuretics. See for example US 4,472,380, especially columns 9 and10 and example 127 thereof; US 4,217,347, especially columns 2-3 and the examples; American J. Hypert. 1(1), 38-41 (1988); Patent Specification No, 2392/86; J. Hyper-tension 1 (Suppl. 2), 384-386 (1983); and Amer. J. Hypert. 1 (3, part 2), 13A-14A, Ab-stract 1226 (1988). However, each of these deal with angiotensin converting enzymeinhibiting drugs other than benazepril and/or diuretics in amounts substantially greaterthan that in the present invention. Probably the most significant reference is Merck’sSouth African Patent Application 83 3903, claiming priority of US Application 383,435.
This reference discloses angiotensin converting enzyme inhibitors of benazepril type in amounts of 2.5-100 mg/day in combination with diuretics generically in the range of 0.5-100 mg/day. Hydrochlorothiazide is only mentioned in amounts of at least 10 mg/day. -2- It is an object of the present invention to provide a pharmaceutical composition to treatraild co aoderace hypertension with s minimum amount of active agent while achieving pressure reductions not achievable with the individual active agentsat the same dosage.
The invention is a fixed ratio low dose combination of 4-6 mg benazepril or a pharmaceu-tically acceptable salt thereof with 80-120 % of % of the initial daily antihypertensiveclinically recommended dose of a thiazide diuretic given as a once daily dosage. Theinventive composition is a daily unit dose for administration to a human adult having mildto moderate hypertension comprising 4 to 6 mg, preferably about 5 mg,benazepril hydrochloride or any other pharmaceutically acceptable salt of benazepril and 80% to 120 %, preferably about 100 %, of % the usual initial antihyper-tensive adult clinical dose of a thiazide diuretic, when such diuretic is used alone.
Pharmaceutically acceptable salts of benazepril are acid addition salts with pharma-cologically harmless acids, e.g. with inorganic acid, for example hydrochloric acid,sulfuric acid or phosphoric acid, or with organic carbonic, sulfonic or sulfo acids, forexample acetic, propionic, glycolic, maleic, fumaric, tartaric, citric, benzoic,methancsulfonic, ethanesulfonic, or 2-hydroxyethanesulfonic acid. Preferred is thehydrochloride, i.e. the acid addition salt with hydrochloric acid.
Preferably the diuretic is selected from bendroflumethiazide (5 mg) 0.5 - 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; methylchlorothiazide (2.5 mg) 0.25 - 0.3S mg polythiazide (2 mg) 0.2 - 0.3 mg; trichlormethiazide (2 mg) 0.2 - 0.3 mg; benzthiazide (50 mg) 0.5 - 0.75 mg; cyclothiazide (2 mg) 0.2 - 0.3 mg.
The usual minimum initial clinical antihypertensive adult dose is shown in parenthesis, followed by the dosage range useful in this invention. The initial clinical dose applied -3- nowadays may differ from the dose given in parenthesis in the list above for some cases.For example hydrochlorothiazide is often given in an initial dose of 25 mg.
More preferably, the thiazide diuretic is selected ftosa chlorothiazide, hydrochlorothiazide,methylchlorothiazide, and chlorthalidone. Most preferably, the thiazide diuredc is selectedfrom chlorothiazide and hydrochlorothiazide; it is in particular hydrochlorothiazide.
The most advantageous composition comprises benazepril hydrochloride and hydrochloro-thiazide in a weight redo of about 0.8 to L for example about 5 mg benazepril hydro-chloride and about 0.25 mg hydrochlorothiazide.
In a clinical double-blind randomized trial with 334 men and women having a sittingdiastolic blood pressure of 95-114 mmHg, the efficacy of the preferred combination of theinvention comprising 5 mg benazepril hydrochloride and 0.25 mg. hydrochlorothiazidegiven once daily was compared with the efficacy of other compositions and of the singledrugs during six weeks. The results are summarized in the following table: 5 mg benazepril^ -5- 625 mg hydrochlorothiazide10 rng benazepril *12.5 mg hydrochlorothiazide20 mg benazepril + 25 mg hydrochlorothiazide20 mg benazepril 25 mg hydrochlorothiazide 20 mg benazepril + 6.25 mg hydrochlorothiazide5 mg benazepril + 25 mg hydrochlorothiazideplacebo a) as the hydrochloride b) reduction of sitting diastolic blood pressure - 9.9 mmHgb> - 9.6 mmHg-13.9 mmHg - 9.8 mmHg - 6.9 mmHg-10.3 mmHg-10.7 mmHg - 3.9 mmHg The clinical results demonstrate that the low dose composition of the invention has asurprising efficacy.
The composition can be put together by methods which are standard in the an in any con- venient dosage form, including tablet, capsule, powder, etc. Any suitable pharmaceutical adjuvant or carrier may also be included. Administration may be by any route by which both benazepril and the thiazide diuretic may be simultaneously administered, but is most -4- preferably oral. The most suitable dosage form is a solid oral dosage form such as a tabletor capsule. While other antihypertensive active agents may be added, most preferably onlybenazepril and only one thiazide diuretic are present in any one composition.
The instant invention will fee more fully understood by reference to the following example,which illustrates, but dees sot limit the invention.
Example: Film-coatcd tablets, containing 6.25 mg 6-chlorO"3s4-dihydro-2H-l^,4-^;azo-thiadiazinc-7-sulfonanude>l,l-dioxidc and 5.00 mg l-carboxymcthyl-3S-(lS-cthoxy-caitx>nyl-3-phenylpropylamino)"2,3A5-tcErahydro-lH-[l]bcnzazepinc-2-onc hydro-chloride are prepared as follows: Ingredients (for 2’000 tablets) core materials 6-chloro-3,4-dihydro-2H-1,2,4-bcnzothiadiazine-7-sulfonamidc- 1,1-dioxide (micronized) 12.50 g l-carboxymcthyl-3S-(lS-ethoxycarbonyl-3-phcnylpropylamino)-2,3,4,5- tctrahydro-lH-[l]bcnzazcpinc-2-one hydrochloride 10.00 g hydroxypropylmethylccUulose 6.00 g hydrogenated castor oil 12.00 g lactose (ground) 423.50 g polyvinyl-polypyrrolidonc 20.00 g Film materials hydroxypropylmethylcellulose 7.34 g polyethyleneglycol 8000 (flakes) 1.34 g talcum 5.32 g titanium dioxide 2.00 g The 6-chloro-3,4-dihydro-2H-1 ^.s4-benzothiadiazinc-7-suiionarnjde-1,1 -dioxide, the1 -carboxymethyl-3S-( 1 S-ethoxycarbonyl"3-phenyipropyIamino)-2,3,4,5-tetrahydro-1H-U]bcnzazepinc-2-one hydrochloride and the core hydroxypropyl-methylcellulose aremixed with part of the lactose. The remaining lactose is added and the mixture isgranulated with water, dried, and milled. The remaining core ingredients arc admixedtherewith and the homogenous mixture is compressed into tablets, which are coated withan aqueous suspension of the above coating materials.
Claims (12)
1. -5- ι. A low dose pharmaceutical composition for treating mild to moderate hypertensioncomprising 4 to 6 mg of benazepril or a pharmaceutically acceptable salt ofbenazepril and a thiazide diuretic in an amount of SO % to 120 % of I of theminimum. recommended initial single adult daily antihypertensive dose ofsaid thiazide diuretic when used alone,, each amount being per unit dose ofsaid composition.
2. A composition according to claim 1 wherein said thiazide diuretic is selected frombendroflumethiazide, chlorthalidone, chlorothiazide, hydrochlorothiazide,hydroP.umethlazide, methylchlorothiazide, polythiazide, trichlormethiazidc, benzthiazide,and cyclothiazide.
3. A composition according to claim 2 wherein said thiazide diuretic ishydrochlorothiazide.
4. A composition according to any of claims 1 to 3 wherein said thiazide diuretic ispresent in an amount which is I of the minimum recommended initial antihypertensivedose when the thiazide diuretic is used alone.
5. A composition according to claim 3 wherein said hydrochlorothiazide is present in anamount of 5 mg io 7.5 mg per dose.
6. A composition according to claim 5 wherein said hydrochlorothiazide is present in anamount of about 6.25 mg per dose.
7. A composition according to any of claims 1 to 6 wherein said benazepril orpharmaceutically acceptable salt thereof is benazepril hydrochloride.
8. A composition according to claim 7 wherein said benazepril hydrochloride is present inan amount of about 5 mg per dose.
9. A composition according to claim 1 comprising 5 mg benazepril hydrochloride and 6.25mg hydrochlorothiazide per dose. -6«
10. A composition according to any of claims Ϊ to 9 which is a tablet, a powder, or acapsule. /
11. A composition according to claim 10 which is an oral tablet or oral capsule.
12. A composition according to claim 1 substantially as herein described with reference to5 the example. F. R. KELLY & CO., AGENTS FOR THE APPLICANTS.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30038389A | 1989-01-23 | 1989-01-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE900233L IE900233L (en) | 1990-07-23 |
| IE61784B1 true IE61784B1 (en) | 1994-11-30 |
Family
ID=23158879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE23390A IE61784B1 (en) | 1989-01-23 | 1990-01-22 | Low dose benazepril/thiazide diuretic composition |
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)
| 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)
| 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 |
-
1990
- 1990-01-08 SE SE9000050A patent/SE506179C2/en not_active IP Right Cessation
- 1990-01-15 CH CH112/90A patent/CH680568A5/de not_active IP Right Cessation
- 1990-01-17 GB GB9001054A patent/GB2227172B/en not_active Expired - Lifetime
- 1990-01-18 LU LU87660A patent/LU87660A1/en unknown
- 1990-01-19 NZ NZ232182A patent/NZ232182A/en unknown
- 1990-01-19 DE DE4001496A patent/DE4001496C2/en not_active Expired - Lifetime
- 1990-01-19 DE DE2001199041 patent/DE10199041I1/en active Pending
- 1990-01-19 CA CA002008126A patent/CA2008126C/en not_active Expired - Lifetime
- 1990-01-19 IT IT47548A patent/IT1239744B/en active IP Right Grant
- 1990-01-19 FR FR909000612A patent/FR2641971B1/en not_active Expired - Lifetime
- 1990-01-22 IL IL93117A patent/IL93117A0/en not_active IP Right Cessation
- 1990-01-22 NL NL9000158A patent/NL194958C/en not_active IP Right Cessation
- 1990-01-22 ZA ZA90429A patent/ZA90429B/en unknown
- 1990-01-22 AU AU48703/90A patent/AU629288B2/en not_active Expired
- 1990-01-22 IE IE23390A patent/IE61784B1/en not_active IP Right Cessation
- 1990-01-22 DK DK199000174A patent/DK175204B1/en not_active IP Right Cessation
- 1990-01-22 AT AT0013590A patent/AT401728B/en not_active IP Right Cessation
- 1990-01-22 JP JP2010782A patent/JP3009694B2/en not_active Expired - Lifetime
- 1990-01-22 BE BE9000074A patent/BE1002736A4/en not_active IP Right Cessation
- 1990-01-22 KR KR1019900000697A patent/KR0141479B1/en not_active IP Right Cessation
- 1990-04-04 SA SA90100151A patent/SA90100151B1/en unknown
-
1992
- 1992-06-25 MX MX9203362A patent/MX9203362A/en unknown
-
1994
- 1994-12-16 SG SG176194A patent/SG176194G/en unknown
-
1995
- 1995-06-22 HK HK98995A patent/HK98995A/en not_active IP Right Cessation
- 1995-12-01 CY CY183595A patent/CY1835A/en unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK9A | Patent expired |