WO1992020342A1 - Novel composition of angiotensin-ii receptor antagonists and calcium channel blockers - Google Patents
Novel composition of angiotensin-ii receptor antagonists and calcium channel blockers Download PDFInfo
- Publication number
- WO1992020342A1 WO1992020342A1 PCT/US1992/003873 US9203873W WO9220342A1 WO 1992020342 A1 WO1992020342 A1 WO 1992020342A1 US 9203873 W US9203873 W US 9203873W WO 9220342 A1 WO9220342 A1 WO 9220342A1
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- WO
- WIPO (PCT)
- Prior art keywords
- tetrazol
- biphenyl
- imidazole
- methyl
- propyl
- Prior art date
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- 239000002333 angiotensin II receptor antagonist Substances 0.000 title claims abstract description 16
- 229940127291 Calcium channel antagonist Drugs 0.000 title claims abstract description 14
- 239000000480 calcium channel blocker Substances 0.000 title claims abstract description 14
- 239000000203 mixture Substances 0.000 title claims abstract description 14
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims abstract description 13
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- 125000000217 alkyl group Chemical group 0.000 claims description 16
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- 238000000034 method Methods 0.000 claims description 7
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- 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 description 1
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
- A61P5/42—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of mineralocorticosteroids
Definitions
- This invention relates to novel pharmaceutical compositions containing an angiotensin-II receptor antagonist from a selected class in combination with a calcium channel blocker from a selected class useful for the treatment of hypertension and for the treatment of congestive heart failure.
- the selected class of angiotensin-II receptor antagonists and the selected class of calcium channel blockers essential as component parts of the novel compositions of this invention are compounds already known in the art as antihypertensive agents.
- Angiotensin-II receptor antagonists useful in compositions of the invention are included in those compounds disclosed in published European Published application 0 324 377 the disclosure of which is
- Calcium channel blockers useful in the compositions of this invention are selected from the group consisting of diltiazem, nifedipine, nitrendipine, nimodipine, niludipine, niguldipine, nicardipine, nisoldipine, amlodipine, felodipine, isradipine, ryosidine,
- verapamil verapamil, gallopamil and tiapamil.
- compositions of this invention contain a calcium channel blocker of the group defined above in combination with an angiotensin-II receptor antagonist compound of the following formula:
- R 1 is CO 2 H; NHSO 2 CF 3 and
- R 2 is H, alkyl of 1 to 4 carbon atoms, halogen, or alkoxy of 1 to 4 carbon atoms;
- R 3 is alkyl, alkenyl or alkynyl of 3 to 7 carbon
- R 4 is H, Cl, Br, I; alkyl of 1 to 4 carbon atoms;
- R 5 is -(CH 2 ) m OR 7 ; -
- R 6 is H, alkyl of 1 to 5 carbon atoms or OR 10 ;
- R 7 is H or alkyl of 1 to 4 carbon atoms
- R 8 is H, alkyl of 1 to 4 carbon atoms, or acyl of 1 to 4 carbon atoms;
- R 9 is CF 3 , alkyl of 1 to 6 carbon atoms or phenyl
- R 10 is H, alkyl of 1 to 6 carbon atoms, cycloalkyl of
- n 1 to 5 or a pharmaceutically acceptable salt thereof.
- Preferred compounds of the above formula are those in which R 1 is
- R 2 is H.
- Illustrative compounds of this preferred scope are:
- the potential antihypertensive effects of the combination of compounds of this invention may be demonstrated by administering the combination of active compounds to conscious spontaneously hypertensive rats. Rats received either orally or intravenously a dose of 0.1-30 mg/kg of the desired calcium channel blocker, or a dose of 0.1-30 mg/kg of the desired angiotensin-II receptor antagonist, or a combination of the two doses of the calcium channel blocker and the angiotensin-II receptor antagonist.
- Arterial blood pressure is
- hypertension are also of value in the management of acute and chronic congestive heart failure.
- These combinations also be expected to be useful in the treatment of secondary hyperaldosteronism, primary and secondary pulmonary hyperaldosteronism, primary and secondary pulmonary hypertension, renal failure such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, end stage renal disease, renal transplant therapy, and the like, renal vascular hypertension, left ventricular dysfunction, diabetic retinopathy and in the management of vascular disorders such as migraine, Raynaud's disease, luminal hyperplasia, and to minimize the atherosclerotic process.
- administration can be any means that effects contact of the active ingredient compounds with the site of action in the body of a warm-blooded animal in need of such treatment.
- administration can be any means that effects contact of the active ingredient compounds with the site of action in the body of a warm-blooded animal in need of such treatment.
- administration can be any means that effects contact of the active ingredient compounds with the site of action in the body of a warm-blooded animal in need of such treatment.
- administration can be any means that effects contact of the active ingredient compounds with the site of action in the body of a warm-blooded animal in need of such treatment.
- administration can be any means that effects contact of the active ingredient compounds with the site of action in the body of a warm-blooded animal in need of such treatment.
- administration can be any means that effects contact of the active ingredient compounds with the site of action in the body of a warm-blooded animal in need of such treatment.
- administration can be any means that effects contact of the active ingredient compounds with the site of action in the body of a warm-
- parenteral i.e., subcutaneous, intravenous
- administration can be by the oral route.
- the combinations of compounds can be administered by any conventional means available for use in
- an angiotensin-II antagonist and calcium channel blocker can be combined with other therapeutic agents, either as individual therapeutic agents or in a combination with additional therapeutic agents.
- an angiotensin-II antagonist and calcium channel blocker can be combined with other therapeutic agents.
- antihypertensives and/or diuretics and/or angiotensin converting enzyme inhibitors such as amiloride
- guanethidene sulfate hydralazine hydrochloride, hydrochlorothiazide, metolazone, metoprolol tartate, methyclothiazide, methyldopa, methyldopate
- benzthiazide quinethazone, ticrynafan, triamterene, acetazolamide, aminophylline, cyclothiazide, ethacrynic acid, furosemide, merethoxylline procaine, sodium ethacrynate, captopril, delapril hydrochloride,
- enalapril enalaprilat, fosinopril sodium, lisinopril, pentopril, quinapril hydrochloride, ramapril, teprotide, zofenopril calcium, diflusinal and the like.
- the combinations of active compounds can be administered alone, but are generally administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard
- a warm-blooded animal is a member of the animal kingdom possessed of a homeostatic mechanism and includes mammals and birds.
- compositions of the invention may contain from 10 to 300 mg of the desired calcium channel blocker and 1 to 100 mg of the angiotensin-II receptor antagonist per unit dose one or more times daily.
- the active ingredients can be administered orally in solid dosage forms, such as capsules, tablets, and powders, or in liquid dosage forms, such as elixirs syrups, and suspensions. They can also be administered parenterally, in sterile liquid dosage forms.
- Gelatin capsules contain the active ingredients and powdered carriers, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours.
- Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective
- Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance.
- water a suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions.
- saline aqueous dextrose (glucose)
- glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions.
- Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilizing agents, and if necessary, buffer substances.
- suitable stabilizing agents such as sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite
- bisulfite, sodium sulfite, or ascorbic acid are suitable stabilizing agents.
- citric acid and its salts and sodium EDTA are also used.
- parenteral solutions can contain
- preservatives such as benzalkonium chloride, methyl- or propylparaben, and chlorobutanol.
- Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, A. Osol, a standard reference text in this field. Useful pharmaceutical dosage-forms for
- a large number of unit capsules are prepared by filling standard two-piece hard gelatin capsules each as with 100 milligrams of powdered active ingredients, 150 milligrams of lactose, 50 milligrams of cellulose, and 6 milligrams magnesium stearate.
- a mixture of active ingredients in a digestible oil such as soybean oil, cottonseed oil or olive oil is combinations prepared and injected by means of a digestible oil such as soybean oil, cottonseed oil or olive oil is combinations prepared and injected by means of a digestible oil such as soybean oil, cottonseed oil or olive oil is combinations prepared and injected by means of a digestible oil such as soybean oil, cottonseed oil or olive oil is combinations prepared and injected by means of a digestible oil such as soybean oil, cottonseed oil or olive oil is combinations prepared and injected by means of a digestible oil such as soybean oil, cottonseed oil or olive oil is combinations prepared and injected by means of a digestible oil such as soybean oil, cottonseed oil or olive oil is combinations prepared and injected by means of a digestible oil such as soybean oil, cottonseed oil or olive oil is combinations prepared and injected by means of a digestible oil such as soybean oil, cottonseed oil or olive oil is combinations prepared and injected by means of a digestible oil such as soybean oil, cottonseed oil
- the dosage unit is 100 milligrams of active ingredients, 0.2 milligrams of colloidal silicon dioxide, 5 milligrams of magnesium stearate, 275 milligrams of microcrystalline cellulose, 11 milligrams of starch and 98.8 milligrams of lactose.
- Appropriate coatings may be applied to increase the dosage unit.
- administration by injection is prepared by stirring 1.5% by weight of active ingredients in 10% by volume propylene glycol. The solution is made to volume with water for injection and sterilized.
- An aqueous suspension is prepared for oral administration so that each 5 milliliters contain 100 milligrams of finely divided active ingredients, 100 milligrams of sodium carboxymethyl cellulose, 5 milligrams of sodium benzoate, 1.0 grams of sorbitol solution, U.S.P., and 0.025 milliliters of vanillin.
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- 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)
- Veterinary Medicine (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)
- Diabetes (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5500110A JP2930252B2 (ja) | 1991-05-15 | 1992-05-14 | アンジオテンシン−▲ｉｉ▼受容体拮抗剤およびカルシウムチャンネルブロッカーの新規組成物 |
| AU20269/92A AU664375B2 (en) | 1991-05-15 | 1992-05-14 | Novel composition of angiotensin-II receptor antagonists and calcium channel blockers |
| KR1019930703429A KR100222627B1 (ko) | 1991-05-15 | 1992-05-14 | 앙기오텐신-ii 수용체 길항제 및 칼슘 채널 차단제의 신규한 조성물 |
| CS932351A CZ281570B6 (cs) | 1991-05-15 | 1992-05-14 | Farmaceutický přípravek obsahující antagonistu receptoru angiotensinu-II a sloučeninu blokující vápníkové kanálky |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US70074091A | 1991-05-15 | 1991-05-15 | |
| US700,740 | 1991-05-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1992020342A1 true WO1992020342A1 (en) | 1992-11-26 |
Family
ID=24814683
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1992/003873 WO1992020342A1 (en) | 1991-05-15 | 1992-05-14 | Novel composition of angiotensin-ii receptor antagonists and calcium channel blockers |
Country Status (11)
Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5663187A (en) * | 1994-03-29 | 1997-09-02 | Merck & Co., Inc. | Treatment of atherosclerosis with angiotensin II receptor blocking imidazoles |
| US6204281B1 (en) | 1998-07-10 | 2001-03-20 | Novartis Ag | Method of treatment and pharmaceutical composition |
| US6245787B1 (en) | 1995-03-16 | 2001-06-12 | Pfizer Inc. | Composition containing amlodipine or a pharmaceutically acceptable salt thereof, and an ACE inhibitor |
| US6395728B2 (en) | 1999-07-08 | 2002-05-28 | Novartis Ag | Method of treatment and pharmaceutical composition |
| WO2001074390A3 (en) * | 2000-04-04 | 2002-05-30 | Pfizer Ltd | The use of a calcium channel blocker for treating renal disorders |
| WO2001082858A3 (de) * | 2000-05-04 | 2002-06-27 | Ipf Pharmaceuticals Gmbh | Neue verbindungen zur behandlung inflammatorischer und kardiovaskulärer erkrankungen |
| EP1234582A4 (en) * | 1999-12-01 | 2003-05-07 | Sankyo Co | COPRESCRIPTION FOR THE TREATMENT OF GLAUCOMA |
| WO2002043807A3 (en) * | 2000-12-01 | 2003-08-14 | Novartis Ag | Combinations of an angiotensin receptor antagonist and an anti-hypertensive drug or a statin, for the treatment of sexual dysfunction |
| RU2210368C1 (ru) * | 1995-06-07 | 2003-08-20 | Санофи Синтелабо | Фармацевтические композиции, содержащие ирбесартан |
| WO2003097045A1 (en) * | 2002-05-17 | 2003-11-27 | Novartis Ag | Combination of organic compounds |
| US7481803B2 (en) * | 2000-11-28 | 2009-01-27 | Flowmedica, Inc. | Intra-aortic renal drug delivery catheter |
| WO2011069038A2 (en) | 2009-12-03 | 2011-06-09 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| WO2013138352A1 (en) | 2012-03-15 | 2013-09-19 | Synergy Pharmaceuticals Inc. | Formulations of guanylate cyclase c agonists and methods of use |
| WO2014151206A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| WO2014151200A2 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| EP2810951A2 (en) | 2008-06-04 | 2014-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| WO2014197720A2 (en) | 2013-06-05 | 2014-12-11 | Synergy Pharmaceuticals, Inc. | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| EP2322174B1 (en) | 1998-07-10 | 2015-09-23 | Novartis Pharma AG | Combined use of valsartan and calcium channel blockers for therapeutic purposes |
| EP2998314A1 (en) | 2007-06-04 | 2016-03-23 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EP3241839A1 (en) | 2008-07-16 | 2017-11-08 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3057471B2 (ja) | 1993-06-07 | 2000-06-26 | 武田薬品工業株式会社 | アンジオテンシンｉｉ介在性諸疾患の予防または治療剤 |
| MXPA05008142A (es) * | 2003-01-31 | 2005-09-30 | Sankyo Co | Medicamento para la profilaxis y el tratamiento de arteriosclerosis e hipertension. |
| TW200833325A (en) * | 2006-12-26 | 2008-08-16 | Daiichi Sankyo Co Ltd | Pharmaceutical composition comprising ascorbic acid |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4983598A (en) * | 1986-11-20 | 1991-01-08 | Synthelabo | Pharmaceutical composition containing diltiazem and angiotensin-converting enzyme inhibitor |
| US5015651A (en) * | 1988-01-07 | 1991-05-14 | E. I. Du Pont De Nemours And Company | Treatment of hypertension with 1,2,4-angiotensin II antagonists |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2020073A1 (en) * | 1989-07-03 | 1991-01-04 | Eric E. Allen | Substituted quinazolinones as angiotensin ii antagonists |
| AU656551B2 (en) * | 1990-12-14 | 1995-02-09 | Smithkline Beecham Corporation | Angiotensin II receptor blocking compositions |
-
1992
- 1992-05-13 NZ NZ242724A patent/NZ242724A/xx not_active IP Right Cessation
- 1992-05-14 IL IL10185892A patent/IL101858A/en not_active IP Right Cessation
- 1992-05-14 WO PCT/US1992/003873 patent/WO1992020342A1/en not_active Application Discontinuation
- 1992-05-14 CA CA002103276A patent/CA2103276A1/en not_active Abandoned
- 1992-05-14 JP JP5500110A patent/JP2930252B2/ja not_active Expired - Lifetime
- 1992-05-14 EP EP92912707A patent/EP0584250A1/en not_active Withdrawn
- 1992-05-14 CZ CS932351A patent/CZ281570B6/cs not_active IP Right Cessation
- 1992-05-14 MX MX9202243A patent/MX9202243A/es unknown
- 1992-05-14 AU AU20269/92A patent/AU664375B2/en not_active Expired
- 1992-05-15 ZA ZA923557A patent/ZA923557B/xx unknown
- 1992-07-01 IE IE153492A patent/IE921534A1/en not_active Application Discontinuation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4983598A (en) * | 1986-11-20 | 1991-01-08 | Synthelabo | Pharmaceutical composition containing diltiazem and angiotensin-converting enzyme inhibitor |
| US5015651A (en) * | 1988-01-07 | 1991-05-14 | E. I. Du Pont De Nemours And Company | Treatment of hypertension with 1,2,4-angiotensin II antagonists |
Non-Patent Citations (4)
| Title |
|---|
| CHEMICAL ABSTRACTS, Volume 109, No. 15, CARINI et al., "Preparation of angiotensin II receptor blocking (phenylalkyl) imidazoles", Abstract No. 129008g; & EP,A,253310, 1988. * |
| CHEMICAL ABSTRACTS, Volume 110, No. 5, WONG et al., "Nonpeptide angiotensin II receptor antagonists. I. Pharmacological characterization of 2-n-bntyl-4chloro-1-(2chlorobenzyl) imidiazole-5-acetic acid, sodium salt (S-8307)", Abstract No. 33491d, J. Pharmacol. Exp. Ther., 247(1), pp. 1-7, 1988. * |
| CHEMICAL ABSTRACTS, Volume 112, No. 13, CARINI et al., "Preparation of (biphenylmethyl)-imidazoles and analogs as antihypertensive agents", Abstract No. 118817f; & EP,A,324377, 1989. * |
| See also references of EP0584250A4 * |
Cited By (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5663186A (en) * | 1994-03-29 | 1997-09-02 | Merck & Co., Inc. | Treatment of atherosclerosis with angiotensin II receptor blocking imidazoles |
| US5663187A (en) * | 1994-03-29 | 1997-09-02 | Merck & Co., Inc. | Treatment of atherosclerosis with angiotensin II receptor blocking imidazoles |
| US6245787B1 (en) | 1995-03-16 | 2001-06-12 | Pfizer Inc. | Composition containing amlodipine or a pharmaceutically acceptable salt thereof, and an ACE inhibitor |
| RU2210368C1 (ru) * | 1995-06-07 | 2003-08-20 | Санофи Синтелабо | Фармацевтические композиции, содержащие ирбесартан |
| US6204281B1 (en) | 1998-07-10 | 2001-03-20 | Novartis Ag | Method of treatment and pharmaceutical composition |
| EP2322174B1 (en) | 1998-07-10 | 2015-09-23 | Novartis Pharma AG | Combined use of valsartan and calcium channel blockers for therapeutic purposes |
| US6395728B2 (en) | 1999-07-08 | 2002-05-28 | Novartis Ag | Method of treatment and pharmaceutical composition |
| EP1344535A3 (en) * | 1999-12-01 | 2004-01-28 | Sankyo Company, Limited | Combined angiotensin II antagonists and adrenaline receptor blockers for treatment of glaucoma |
| EP1234582A4 (en) * | 1999-12-01 | 2003-05-07 | Sankyo Co | COPRESCRIPTION FOR THE TREATMENT OF GLAUCOMA |
| US7307096B2 (en) | 1999-12-01 | 2007-12-11 | Sankyo Company, Limited | Combined agents for treatment of glaucoma |
| WO2001074390A3 (en) * | 2000-04-04 | 2002-05-30 | Pfizer Ltd | The use of a calcium channel blocker for treating renal disorders |
| WO2001082858A3 (de) * | 2000-05-04 | 2002-06-27 | Ipf Pharmaceuticals Gmbh | Neue verbindungen zur behandlung inflammatorischer und kardiovaskulärer erkrankungen |
| US7481803B2 (en) * | 2000-11-28 | 2009-01-27 | Flowmedica, Inc. | Intra-aortic renal drug delivery catheter |
| WO2002043807A3 (en) * | 2000-12-01 | 2003-08-14 | Novartis Ag | Combinations of an angiotensin receptor antagonist and an anti-hypertensive drug or a statin, for the treatment of sexual dysfunction |
| EP1353727A2 (en) * | 2000-12-01 | 2003-10-22 | Novartis AG | Combinations of an angiotensin receptor antagonist and an anti-hypertensive drugor a statin, for the treatment of sexual dysfunction |
| US8101599B2 (en) | 2002-05-17 | 2012-01-24 | Novartis Ag | Pharmaceutical composition containing anti-hypertensive agents |
| WO2003097045A1 (en) * | 2002-05-17 | 2003-11-27 | Novartis Ag | Combination of organic compounds |
| EP2998314A1 (en) | 2007-06-04 | 2016-03-23 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EP2810951A2 (en) | 2008-06-04 | 2014-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EP3241839A1 (en) | 2008-07-16 | 2017-11-08 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| WO2011069038A2 (en) | 2009-12-03 | 2011-06-09 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| EP2923706A1 (en) | 2009-12-03 | 2015-09-30 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia |
| WO2013138352A1 (en) | 2012-03-15 | 2013-09-19 | Synergy Pharmaceuticals Inc. | Formulations of guanylate cyclase c agonists and methods of use |
| EP3708179A1 (en) | 2012-03-15 | 2020-09-16 | Bausch Health Ireland Limited | Formulations of guanylate cyclase c agonists and methods of use |
| EP4309673A2 (en) | 2012-03-15 | 2024-01-24 | Bausch Health Ireland Limited | Formulations of guanylate cyclase c agonists and methods of use |
| WO2014151200A2 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| WO2014151206A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| WO2014197720A2 (en) | 2013-06-05 | 2014-12-11 | Synergy Pharmaceuticals, Inc. | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| EP4424697A2 (en) | 2013-06-05 | 2024-09-04 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
Also Published As
| Publication number | Publication date |
|---|---|
| IL101858A0 (en) | 1992-12-30 |
| MX9202243A (es) | 1992-11-01 |
| CZ281570B6 (cs) | 1996-11-13 |
| IL101858A (en) | 1996-08-04 |
| EP0584250A1 (en) | 1994-03-02 |
| AU664375B2 (en) | 1995-11-16 |
| AU2026992A (en) | 1992-12-30 |
| NZ242724A (en) | 1994-09-27 |
| CA2103276A1 (en) | 1992-11-16 |
| JP2930252B2 (ja) | 1999-08-03 |
| ZA923557B (en) | 1993-11-15 |
| IE921534A1 (en) | 1992-11-18 |
| CZ235193A3 (en) | 1994-03-16 |
| EP0584250A4 (enrdf_load_stackoverflow) | 1994-03-30 |
| JPH06508128A (ja) | 1994-09-14 |
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