- COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING SALT SENSITIVITY OF BLOOD PRESSURE
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To characterize the urinary exosome miRNome, microarrays were used to identify the miRNA spectrum present within urinary exosomes from ten individuals that were previously classified for their salt sensitivity status. The present application discloses distinct patterns of selected exosomal miRNA expression that were different between salt-sensitive (SS), salt-resistant (SR), and inverse salt-sensitive (ISS) individuals. These miRNAs can be useful as biomarkers either individually or as panels comprising multiple miRNAs. The present invention provides compositions and methods for identifying, diagnosing, monitoring, and treating subjects with salt sensitivity of blood pressure. The applications discloses panels of miRNAs useful for comparing profiles, and in some cases one or more of the miRNAs in a panel can be used. The miRNAs useful for distinguishing SS and SR or ISS and SR subjects. One or more of the 45 miRNAs can be used. Some of the miRNAs have not been previously reported to be circulating. See those miRNAs with asterisks in FIG. 1 and below. The present invention encompasses the use of one or more of these markers for identifying and diagnosing SR, SS, and ISS subjects.
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- An efficient, commercially viable, and safe process for preparation of losartan potassium, an angiotensin II receptor antagonist
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An efficient, commercially viable and safe process for the preparation of losartan potassium, an antihypertensive drug substance, with an overall yield of 55.5% and ~99.9% purity (including five chemical reactions and two recrystallizations) and meeting all other regulatory requirements is described. Formation and control of all the possible impurities are also described.
- Madasu, Suri Babu,Vekariya,Koteswaramma, Ch,Islam, Aminul,Sanasi, Paul Douglas,Korupolu, Raghu Babu
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p. 2025 - 2030
(2013/02/25)
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- NOVEL ZINC AZIDE COMPLEX AND A PROCESS FOR PREPARING TETRAZOLE DERIVATIVES USING THE SAME
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The present invention relates to a novel zinc azide complex. The present invention also relates to a process for preparing 5-substituted-1H-tetrazole derivatives from nitrile derivatives by using the zinc azide complex. According to the present invention, in particular, pharmaceutically active compounds for treating hypertension or intermediates useful for preparation thereof can be prepared effectively.
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- AN IMPROVED PROCESS FOR PREPARING LOSARTAN POTASSIUM
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The present invention relates to an improved process for preparing Losartan Potassium of formula (I).
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Page/Page column 12
(2010/04/06)
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- Process for the Preparation of Losartan
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The invention relates to an improved process for the preparation of Losartan. The process comprising reacting 2-n-butyl-4-chloro-5-formyl imidazole with 2-(4-bromomethyl) benzonitrile in the presence of a phase transfer catalyst and an alkali, and reducing the resulting cyano aldehyde to produce a cyano alcohol which is further reacted with sodium azide in N-methyl pyrrolidinone and a salt to produce Losartan.
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Page/Page column 8
(2010/08/07)
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- Process for the preparation of losartan
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The invention relates to a improved process for the preparation of Losartan and its potassium salt, which comprises: (i) reacting bromo OTBN with BCFI in the presence of a base and a phase transfer catalyst to produce a cyano aldehyde; reacting the formed cyano aldehyde with sodium azide in the presence of tributyl tin chloride to produce aldehyde tetrazole; reducing the formed aldehyde tetrazole with sodium borohydride to produce Losartan; and, if desired, converting the formed Losartan to its potassium salt by known method.
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Page/Page column 8
(2010/09/07)
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- A PROCESS FOR PREPARATION OF LOSARTAN POTASSIUM FORM I
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The present invention relates to a process for preparation of Losartan potassium Form I.
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Page/Page column 8
(2010/05/13)
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- A process for the preparation of angiotensin II antagonistic compounds
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A process for the preparation of angiotensin II antagonists and novel intermediates useful for the synthesis thereof.
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Page/Page column 7
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF ANGIOTENSIN II ANTAGONISTIC COMPOUNDS
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A process for the preparation of angiotensin II antagonists and novel intermediates useful for the synthesis thereof.
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Page/Page column 5
(2010/11/26)
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- A process for the preparation of losartan derivatives by chlorination and reduction of the respective 1H-imidazole-5-carbaldehydes
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The invention provides a process for the preparation of a sartan derivative of formula (I): wherein R = C2-C7 straight or branched alkyl or C3-C9 cycloalkyl, or a pharmaceutically acceptable salt thereof, comprising the steps of chlorinating and reducing, in any order, a compound of formula (III): wherein R is defined as above to form a compound of formula (VI), wherein R is defined as above and then deprotecting said compound of formula (VI) to obtain the sartan derivative of formula (I), and optionally converting said sartan derivative into one of its pharmaceutically acceptable salts. A preferred embodiment of this invention is a process for the preparation of losartan and, particularly, its potassium salt.
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Page/Page column 12
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF LOSARTAN
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The invention relates to a improved process for the preparation of Losartan and its potassium salt, which comprises (i) reacting bromo OTBN with BCFI in the presence of a base and a phase transfer catalyst to get cyano aldehyde, reacting the cyano aldehyde sodium azide in the presence of tributyl tin chloride to form aldehyde tetrazole , reducing the aldehyde tetrazole with sodium borohydride to give Losartan and , if desired , converting it to its potassium salt by known method .
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Page/Page column 17-18; 20-21
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF LOSARTAN AND ITS SALTS
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The invention relates to the preparation of losartan and its salts (e.g., losartan potassium). More particularly, the invention relates to the preparation of losartan and its salts (e.g., losartan potassium) in a simplified process that provides higher purity losartan potassium and losartan potassium having larger crystal sizes. The invention further includes formulating losartan, its salts (e.g., losartan potassium ) and/or in vivo cleavable prodrugs thereof (collectively "the compounds of the invention") into readily usable dosage units for the therapeutic treatment (including prophylactic treatment) of mammals, including humans.
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Page/Page column 12-13
(2008/06/13)
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- METHOD FOR PRODUCING METAL SALTS OF LOSARTAN
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A method for producing metal salts of Losartan of the following formula (I) by treating Losartan free acid with a basic metal salt in a solvent proposes to use a solvent comprising a mixture of isopropyl alcohol and t-butyl methyl ether.
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Page/Page column 9-10
(2008/06/13)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF LOSARTAN
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The invention relates to an improved process for the preparation of Losartan. Which comprises reacting 2-n-butyl-4-chloro-5-formyl imidazole with 2-(4-bromomethyl) benzonitrile in the presence of a phase transfer catalyst and alkali, and reducing resulting cyano aldehyde to get cyano alcohol which is further reacted with sodium azide in N-methyl pyrrolidinone and a salt to produce Losartan .
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Page/Page column 9; 14; 17
(2008/06/13)
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- AN IMPROVED PROCESS FOR THE MANUFACTURE OF LOSARTAN POTASSIUM
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The present invention relates to an improved process for the manufacture of Losartan potassium. The process comprises of condensation of 2-butyl-4-chloro-5-formyl imidazole with 2-cyano-4-bromomethyl biphenyl in a biphasic solvent system under phase transfer catalysis followed by insitu reduction using sodium borohydride. The obtained product is converted to Losartan by treating with sodium azide and an amine salt. Losartan is then converted to its potassium salt by treating it with potassium hydroxide in alcohol.
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Page/Page column 14
(2008/06/13)
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- METHOD FOR PREPARING LOSARTAN
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The present invention relates to a simple and efficient method for preparing losartan, which comprises the steps of reacting a nitrile compound with triethylamine hydrochloride and sodium azide in an organic solvent; and crystallizing losartan directly from the reaction solution.
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- Process for preparing losartan
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A process for preparing losartan, comprising reacting trityl losartan with an aqueous acid.
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Page/Page column 3-4
(2008/06/13)
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- Stable non-crystalline formulation comprising losartan
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One or more embodiments of the invention provide various novel formulations, and tablet dosage forms, comprising losartan that are non-crystalline, stable, and/or otherwise improvements over known losartan formulations. One or more embodiments of the invention further provide methods for preparing the formulation, methods for preparing the tablet dosage form, and to methods of administering the tablet dosage and/or formulation comprising losartan. The losartan-containing formulations may be administered to a user to treat hypertension, and related conditions.
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Page/Page column 21
(2008/06/13)
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- A METHOD OF REMOVING THE TRIPHENYLMETHANE PROTECTING GROUP
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A method of removing the triphenylmethane protecting group from 1-triphenylmethyl-5-(4'-subst. methyl-1,1‘-biphenyl-2-yl)-1H-tetrazoles of general formula I wherein R represents the groups of formulae and where R1, R2 and R3 can be H, a halogen, an unbranched or branched C1-C5 alkyl, C1-C5 hydroxyalkyl, Cl-C5 alkoxy, C1-C5 alkoxymethyl or benzyl, or wherein R2 and R3 can form together a saturated or unsaturated C5-C7 ring, optionally an unsubstituted or substituted aromatic ring, is carried out by solvolysis in a simple anhydrous Cl to C5 alcohol in a neutral or slightly basic medium. The method is suitable for the preparation of drugs, such as the potassium salts of losartan, irbesartan or valsartan or candesartan cilexetil.
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Page/Page column 13-14
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF LOSARTAN POTASSIUM FORM I
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The present invention relates to a novel method for preparing trityl losartan and losartan potassium form I.
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Page/Page column 13
(2008/06/13)
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- A process for the preparation of crystalline losartan potassium
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A process for the preparation of crystalline losartan potassium and crystalline hydrate losartan potassium.
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Page/Page column 4
(2008/06/13)
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- Process for the preparation of crystalline losartan potassium
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A process for the preparation of crystalline losartan potassium and crystalline hydrate losartan potassium.
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Page/Page column 2
(2008/06/13)
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- AN IMPROVED PROCESS FOR THE SYNTHESIS OF LOSARTAN POTASSIUM
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Improved processes using primary, secondary and tertiary alcohols and with safer mode of introduction of the reagent and reaction conditions are described. Further, the process of manufacture of Losaratan potassium by use of alkali metal salt such as Potassium carbonate is disclosed. A process for preparation of the polymorphic Form I of Losartan potassium is also disclosed herein.
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Page/Page column 11-12
(2008/06/13)
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- Process for the synthesis of losartan potassium
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Improved processes using primary, secondary and tertiary alcohols and with safer mode of introduction of the reagent and reaction conditions are described. Further, the process of manufacture of Losartan potassium by use of alkali metal salt such as Potassium carbonate is disclosed. A process for preparation of the polymorphic Form I of Losartan potassium is also disclosed herein.
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- Losartan potassium synthesis
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A process for the synthesis of Losartan Potassium by reacting Trityl Losartan in a primary alcohol with potassium tertiary alkoxide.
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- A PROCESS FOR THE SYNTHESIS OF LOSARTAN POTASSIUM
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A process for the synthesis of Losartan Postassium by reacting Trityl Losartan in a primary alcohol with potassium tertiary alkoxide.
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- Crystalline form of losartan potassium
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A compound that is a crystalline Form III of losartan potassium is provided. Also provided are compositions containing the compound and methods for its preparation.
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Page/Page column 5-6
(2010/02/06)
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- PREPARATION OF NEW PHARMACEUTICALLY SUITABLE SALT OF LOSARTAN AND FORMS THEREOF WITH NEW PURIFICATION AND ISOLATION METHODS
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Pharmaceutically suitable crystalline and amorphous alkali and earth-alkali salts of 2-n-butyl-4-chloro-5-h idroxymethyl-1-[[2'-(1 H-tetrazole-5-yl)[1.1'-biphenyl]-4-yl]-1 H-imidazole have been prepared and new manufacturing, purification and isolation procedure for said salts in high purity have been described. Stable pharmaceutical compositions containing new crystalline potassium salts of 2-n-butyl-4-chloro-5-hidroxymethyl-1-[[2'-(1 H-tetrazole-5-yl)[1.1'-biphenyl]-4-yl]-1 H-imidazole have been prepared.
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Page/Page column 54-55
(2008/06/13)
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- LOSARTAN POTASSIUM POLYMORPHS AND PROCESS FOR THE PREPARATION THEREOF
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Losartan potassium polymorphs, identified as Losartan potassium crystalline hydrate, Losartan potassium amorphous and Losartan potassium modification crystalline III, a process for their preparation, pharmaceutical compositions containing them and their use in therapy.
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- PROCESSES FOR PREPARING LOSARTAN AND LOSARTAN POTASSIUM
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Losartan is prepared by acid catalyzed cleavage of a triarylmethyl group from a triarylmethyl-substituted losartan derivative in a diluent comprising liquid ketone. The reaction mixture is basified and liquid ketone is evaporated from the mixture leaving a residue from which a triarylmethyl alcohol and losartan are each obtained in high yield and high purity. In addition, losartan potassium is prepared by a process that is more convenient that those previously known in the art in which losartan is contacted with potassium ions in substantially pure liquid alcohol and losartan potassium is precipitated from the alcohol.
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Page/Page column 17-18
(2008/06/13)
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- Process for the synthesis of a known tetrazol derivative
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The invention relates to a process for the synthesis of losartan potassium of formula (I), chemical name: 2-n-butyl-4-chloro-1-[(2'-(tetrazol-5-yl)-1,1'biphenyl-4-yl)-methyl]-imidazol-5-methanol potassium, starting from 2-n-butyl-4-chloro-1-[(2'-(2-triphenylmetyl-2H-tetrazol-5-yl)-1,1'-biphenyl-4-yl)-methyl]-1H-imidazol-4-methanol of formula (III). According to the process the compound of formula (III) is reacted in an alcohol of formula (VI),-wherein the meaning of R is C1-C4 straight chain alkyl group-with 0.1-1 equivalent of potassium hydroxide. The final product of formula (I) is isolated after crystallizing out by changing the solvent to an aprotic or weakly protic solvent (I).
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- Use of an angiotensin II receptor antagonist for the preparation of drugs to increase the survival rate of renal transplant patients
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The present invention relates to the use, for the preparation of drugs to increase the survival rate of transplant patients, including renal and heart transplant patients, of a therapeutically effective amount of an angiotension II receptor antagonist compound, such as the class of substituted imidazoles represented by formula (I) and in particular by losartan potassium, 2-butyl-4-chloro-[(2′-tetrazol-5-yl)biphenyl-4-il]methyl]-5-(hydroxymethyl)imidazole potassium salt.
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- Crystalline or crystallized acid addition salt of losartan and purification method of losartan
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The present invention provides a crystalline or crystallized acid addition salt of Losartan useful for obtaining highly pure 2-n-butyl-4-chloro-1-[[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-1H-imidazole-5-methanol (Losartan), and a purification method of Losartan that includes production of the crystalline or crystallized acid addition salt.
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Referential example 1-2
(2008/06/13)
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- PROCESS FOR THE CRYSTALLIZATION OF LOSARTAN
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Losartan potassium is an angiotensin II antagonist useful in the treatment of hypertension and congestive heart failure. This invention relates to the process for the controlled crystallization of losartan potassium utilizing anti-solvent addition combined with massive seeding in order to obtain the desired crystal morphology and bulk physical properties necessary for successful formulation.
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- Process for the crystalization of losartan
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Losartan potassium is an angiotensin II antagonist useful in the treatment of hypertension and congestive heart failure. STR1 This invention relates to the process for the controlled crystallization of losartan potassium utilizing anti-solvent addition combined with massive seeding in order to obtain the desired crystal morphology and bulk physical properties necessary for successful formulation.
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- INSULIN SENSITIVITY WITH ANGIOTENSIN II RECEPTOR BLOCKING IMIDAZOLES
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This invention relates to a novel method of using an Angiotensin II antagonist for the improvement of insulin sensitivity alone or in conjunction with the treatment of hypertension. Angiotensin II antagonists such as the class of substituted imidazoles represented by formula I: STR1 and specifically by Losartan, 2-butyl-4-chloro-1-[(2'-tetrazol-5-yl)biphenyl-4-yl]methyl]-5-(hydroxymethyl)imidazole potassium salt.
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- Polymorphs of losartan and the process for the preparation of form II of losartan
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Polymorphic forms of Losartan (Formula I) STR1 and a process for the preparation of Form II of Losartan. Losartan is known to be useful in the treatment of hypertension.
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- Treatment of atherosclerosis with angiotensin II receptor blocking imidazoles
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A method of treatment for atherosclerosis and/or reducing cholesterol using an angiotensin II antagonist. This method of treatment can be used in conjunction with the treatment of hypertension. Substituted imidazoles such as STR1 are useful as angiotensin II receptor antagonists for this method of treatment. A method of treatment for atherosclerosis and/or reducing cholesterol using an angiotensin II receptor antagonist in combination with an HMG-Co A reductase inhibitor. A method of treatment for atherosclerosis and/or reducing cholesterol using an angiotensin II receptor antagonist in combination with an HMG-Co A reductase inhibitor and an angiotensin converting enzyme inhibitor. Also within the scope of this invention are pharmaceutical compositions for this method of use.
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- Method for the treatment of cardiac and of vascular hypertrophy and hyperplasia
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The invention relates to a method for the treatment of cardiac and of vascular hypertrophy and/or hyperplasia by administration of angiotensin II receptor blockers, preferably of the imidazole, pyrrole, pyrazole, triazole or tetrazole type.
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