CA2008126C - Low dose benazepril/thiazide diuretic composition - Google Patents
Low dose benazepril/thiazide diuretic compositionInfo
- Publication number
- CA2008126C CA2008126C CA002008126A CA2008126A CA2008126C CA 2008126 C CA2008126 C CA 2008126C CA 002008126 A CA002008126 A CA 002008126A CA 2008126 A CA2008126 A CA 2008126A CA 2008126 C CA2008126 C CA 2008126C
- Authority
- CA
- Canada
- Prior art keywords
- composition
- benazepril
- hydrochlorothiazide
- thiazide diuretic
- dose
- 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.)
- Expired - Lifetime
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
Abstract
A fixed ratio low dose combination of benazepril and a thiazide diuretic is disclosed for treating hypertension. Particularly preferred is a composition having about 4-6 mg of benazepril hydrochloride and about 5-7.5 mg of hydrochlorothiazide per dosage form.
Description
4-17427/=/CGC 1398 Law dose benazepril/thiazide diuretic composition The invention relates to a Pharmaceutical composition for treating mild to moderate hypertension containing the angiotensin converting enzyme inhibitar benazepril in combi-nation with thiazide diuretics, and to a method of treatment of hypertension utilizing this composition.
Benazepril hydrochloride is a new orally active, non-sulfhydril containing, angiotensin converting enzyme inhibitor having the structure HCt ..,~~~~~ NH O
N
O
COOH
The compound is described in U.S. 4,410,520. Thiazide diuretics, the second component of the instant combination, have long been a mainstay of antihypertensive therapy. All of the 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 some literature published in recent years on combining angiotensin converting enzyme inhibitors with thiazide diuretics. See for example US 4,472,380, especially columns 9 and and example 127 thereof; US 4,217,347, especially columns 2-3 and the examples;
American J. Hypert. 1(1), 38-41 (1988); European patent application 0,215,357;
J. I-Iyper-tension 1 (Suppl. 2), 384-386 (I983); and Amer. J. Hypert. 1 (3, part 2), 13A-14A, Ab-stract 1226 (1988). However, each of these deal with angiotensin converting enzyme inhibiting drugs other than benazepril and/or diuretics in amounts substantially greater than that in the present invention. Probably the most significant reference is Merck's South 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. I-Iydrochlorothiazide is only mentioned in amounts of at least 10 mg/day.
2oos12s It is an object of the present invention to provide a pharmaceutical composition to treat and a method of treating mild to moderate hypertension with a minimum amount of active agent while achieving pressure reductions not achievable with the individual active agents at 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 t/g of the initial daily antihypertensive clinically recommended dose of a thiazide diuretic given as a once daily dosage. The inventive composition is a daily unit dose for administration to a human adult having mild ;to moderate hypertension comprising about 4 to about 6 mg, preferably about 5 mg, benazepril hydrochloride or any other pharmaceutically acceptable salt of benazepril and about 80 % to about 120 %, preferably about 100 %, of 1/s 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, for example acetic; propionic, glycolic; malefic) fumaric, tartaric) citric, benzoic, methanesulfonic, ethanesulfonic) or 2-hydroxyethanesulfonic acid. Preferred is the hydrochloride, 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 - 0.38 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 ~Q~~~~6 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 from chlorothiazide, hydrochlorothiazide, methylchlorothiazide, and chlorthalidone. Most preferably, the thiazide diuretic is selected from chlorothiazide and hydrochlorothiazide; it is in particular hydrochlorothiazide.
The most advantageous composition comprises benazepril hydrochloride and hydrochloro-thiazide in a weight ratio of about 0.8 to 1, for example about 5 mg benazepril hydro-chloride and about 6.25 mg hydrochlorothiazide.
In a clinical double-blind randomized trial with 33~ men and women having a sitting diastolic blood pressure of 95-114 mmHg, the efficacy of the preferred combination of the invention comprising 5 mg benazepril hydrochloride and 6.25 mg hydrochlorothiazide given once daily was compared with the efficacy of other compositions and of the single drugs during six weeks. The results are summarized in the following table:
mg benazeprila> + 6.25 mg hydrochlorothiazide- 9.9 mmHgb>
mg benazepril + 12.5 mg hydrochlorothiazide- 9.6 mmHg mg benazepril + 25 mg hydrochlorothiazide-13.9 mmI-Ig 20 mg benazepril - 9.8 mmHg mg hydrochlorothiazide - 6.9 mmHg 20 mg benazepril + 6.25 mg hydrochlorothiazide-10.3 mmHg 5 mg benazepril + 25 mg hydrochlorothiazide-10.7 mmHg placebo - 3.9 mmHg a) as the hydrochloride b) reduction of sitting diastolic blood pressure The clinical results demonstrate that the low dose composition of the invention has a surprising efficacy.
The composition can be put together by methods which are standard in the art 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 i~~~~~.~~i preferably oral. The most suitable dosage form is a solid oral dosage form such as a tablet or capsule. While other antihypertensive active agents may be added, most preferably only benazepril and only one thiazide diuretic are present in any one composition.
The instant invention will be more fully understood by reference to the following example, which illustrates, but does not limit the invention.
Example: Film-coated tablets, containing 6.25 mg 6-chloro-3,4-dihydro-2I-i-1,2,4-benzo-thiadiazine-7-sulfonamide-1,1-dioxide and 5.00 mg 1-carboxymethyl-3S-(1S-ethoxy-carbonyl-3-phenylpropylamino)-2,3,4,5-tetrahydro-1H-[1]benzazepine-2-one hydro-chloride are prepared as follows:
I~~redients (for 2'000 tablets) core materials 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide (micronized) 12.50 g 1-carboxymethyl-3S-( 1 S-ethoxycarbonyl-3-phenylpropylamino)-2,3,4,5--tetrahydro-1H-[1]benzazepine-2-one hydrochloride10.00 g hydroxypropylmethylcellulose 6.00 g hydrogenated castor oil 12.00 g lactose (ground) 423.50 g polyvinyl-polypyrrolidone 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-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide, the 1-carboxymethyl-3S-( 1 S-ethoxycarbonyl-3-phenylpropylamino)-2,3,4,5-tetrahydro-1H-[1]benzazepine-2-one hydrochloride and the core hydroxypropyl-methylcellulose are mixed with part of the lactose. The remaining lactose is added and the mixture is granulated with water, dried, and milled. The remaining core ingredients are admixed therewith and the homogenous mixture is compressed into tablets, which are coated with an aqueous suspension of the above coating materials.
Benazepril hydrochloride is a new orally active, non-sulfhydril containing, angiotensin converting enzyme inhibitor having the structure HCt ..,~~~~~ NH O
N
O
COOH
The compound is described in U.S. 4,410,520. Thiazide diuretics, the second component of the instant combination, have long been a mainstay of antihypertensive therapy. All of the 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 some literature published in recent years on combining angiotensin converting enzyme inhibitors with thiazide diuretics. See for example US 4,472,380, especially columns 9 and and example 127 thereof; US 4,217,347, especially columns 2-3 and the examples;
American J. Hypert. 1(1), 38-41 (1988); European patent application 0,215,357;
J. I-Iyper-tension 1 (Suppl. 2), 384-386 (I983); and Amer. J. Hypert. 1 (3, part 2), 13A-14A, Ab-stract 1226 (1988). However, each of these deal with angiotensin converting enzyme inhibiting drugs other than benazepril and/or diuretics in amounts substantially greater than that in the present invention. Probably the most significant reference is Merck's South 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. I-Iydrochlorothiazide is only mentioned in amounts of at least 10 mg/day.
2oos12s It is an object of the present invention to provide a pharmaceutical composition to treat and a method of treating mild to moderate hypertension with a minimum amount of active agent while achieving pressure reductions not achievable with the individual active agents at 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 t/g of the initial daily antihypertensive clinically recommended dose of a thiazide diuretic given as a once daily dosage. The inventive composition is a daily unit dose for administration to a human adult having mild ;to moderate hypertension comprising about 4 to about 6 mg, preferably about 5 mg, benazepril hydrochloride or any other pharmaceutically acceptable salt of benazepril and about 80 % to about 120 %, preferably about 100 %, of 1/s 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, for example acetic; propionic, glycolic; malefic) fumaric, tartaric) citric, benzoic, methanesulfonic, ethanesulfonic) or 2-hydroxyethanesulfonic acid. Preferred is the hydrochloride, 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 - 0.38 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 ~Q~~~~6 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 from chlorothiazide, hydrochlorothiazide, methylchlorothiazide, and chlorthalidone. Most preferably, the thiazide diuretic is selected from chlorothiazide and hydrochlorothiazide; it is in particular hydrochlorothiazide.
The most advantageous composition comprises benazepril hydrochloride and hydrochloro-thiazide in a weight ratio of about 0.8 to 1, for example about 5 mg benazepril hydro-chloride and about 6.25 mg hydrochlorothiazide.
In a clinical double-blind randomized trial with 33~ men and women having a sitting diastolic blood pressure of 95-114 mmHg, the efficacy of the preferred combination of the invention comprising 5 mg benazepril hydrochloride and 6.25 mg hydrochlorothiazide given once daily was compared with the efficacy of other compositions and of the single drugs during six weeks. The results are summarized in the following table:
mg benazeprila> + 6.25 mg hydrochlorothiazide- 9.9 mmHgb>
mg benazepril + 12.5 mg hydrochlorothiazide- 9.6 mmHg mg benazepril + 25 mg hydrochlorothiazide-13.9 mmI-Ig 20 mg benazepril - 9.8 mmHg mg hydrochlorothiazide - 6.9 mmHg 20 mg benazepril + 6.25 mg hydrochlorothiazide-10.3 mmHg 5 mg benazepril + 25 mg hydrochlorothiazide-10.7 mmHg placebo - 3.9 mmHg a) as the hydrochloride b) reduction of sitting diastolic blood pressure The clinical results demonstrate that the low dose composition of the invention has a surprising efficacy.
The composition can be put together by methods which are standard in the art 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 i~~~~~.~~i preferably oral. The most suitable dosage form is a solid oral dosage form such as a tablet or capsule. While other antihypertensive active agents may be added, most preferably only benazepril and only one thiazide diuretic are present in any one composition.
The instant invention will be more fully understood by reference to the following example, which illustrates, but does not limit the invention.
Example: Film-coated tablets, containing 6.25 mg 6-chloro-3,4-dihydro-2I-i-1,2,4-benzo-thiadiazine-7-sulfonamide-1,1-dioxide and 5.00 mg 1-carboxymethyl-3S-(1S-ethoxy-carbonyl-3-phenylpropylamino)-2,3,4,5-tetrahydro-1H-[1]benzazepine-2-one hydro-chloride are prepared as follows:
I~~redients (for 2'000 tablets) core materials 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide (micronized) 12.50 g 1-carboxymethyl-3S-( 1 S-ethoxycarbonyl-3-phenylpropylamino)-2,3,4,5--tetrahydro-1H-[1]benzazepine-2-one hydrochloride10.00 g hydroxypropylmethylcellulose 6.00 g hydrogenated castor oil 12.00 g lactose (ground) 423.50 g polyvinyl-polypyrrolidone 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-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide, the 1-carboxymethyl-3S-( 1 S-ethoxycarbonyl-3-phenylpropylamino)-2,3,4,5-tetrahydro-1H-[1]benzazepine-2-one hydrochloride and the core hydroxypropyl-methylcellulose are mixed with part of the lactose. The remaining lactose is added and the mixture is granulated with water, dried, and milled. The remaining core ingredients are admixed therewith and the homogenous mixture is compressed into tablets, which are coated with an aqueous suspension of the above coating materials.
Claims (11)
1. A low dose pharmaceutical composition for treating mild to moderate hypertension comprising about 4 to about 6 mg of benazepril or a pharmaceutically acceptable salt of benazepril and a thiazide diuretic in an amount of about 80 % to 120 % of 1/8 of the minimum recommended initial antihypertensive dose of said thiazide diuretic when used alone, each amount being per unit dose of said composition.
2. The composition of claim 1 wherein said thiazide diuretic is selected from bendroflumethiazide, chlorthalidone, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methylchlorothiazide, polythiazide, trichlormethiazide, benzthiazide, and cyclothiazide.
3. The composition of claim 2 wherein said thiazide diuretic is hydrochlorothiazide.
4. The composition of claim 1 wherein said thiazide diuretic is present in an amount which is 1/8 of the minimum recommended initial antihypertensive dose when the thiazide diuretic is used alone.
5. The composition of claim 3 wherein said hydrochlorothiazide is present in an amount of about 5 mg to about 7.5 mg per dose.
6. The composition of claim 5 wherein said hydrochlorothiazide is present in an amount of about 6.25 mg per dose.
7. The composition of claim 1 wherein said benazepril or pharmaceutically acceptable salt thereof is benazepril hydrochloride.
8. The composition of claim 7 wherein said benazepril hydrochloride is present in an amount of about 5 mg per dose.
9. The composition of claim 1 comprising 5 mg benazepril hydrochloride and 6.25 mg hydrochlorothiazide per dose.
10. The composition of claim 1 which is a tablet, a powder, or a capsule.
11. The composition of claim 1 which is an oral tablet or oral capsule.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30038389A | 1989-01-23 | 1989-01-23 | |
| US300,383 | 1989-01-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2008126A1 CA2008126A1 (en) | 1990-07-23 |
| CA2008126C true CA2008126C (en) | 1999-11-09 |
Family
ID=23158879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002008126A Expired - Lifetime CA2008126C (en) | 1989-01-23 | 1990-01-19 | 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 |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |