183 results about "Olmesartan" patented technology

The present invention relates to an improved process for the manufacture of olmesartan and pharmaceutically acceptable salts and esters thereof as an active ingredient of a medicament for the treatment of hypertension and related diseases and conditions.

The invention relates to the technical field of a preparation method for an olmensartan medoxomil with a low-level impurity. With the invention, 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylic acid ethyl ester and 4-[12-(triphenylmethyl tetrazole-5-yl) phenyl] benzyl bromide are adopted as raw materials, and are sequentially subjected to an alkylating, a hydrolysis and a esterification, and a last process of a protective group removing to obtain the olmensartan medoxomil with high impurity. Content of single impurity of the olmensartan medoxomil is less than 0.1%. In the prior art, the olmensartan medoxomil has disadvantages of a variety of the impurities, high content of the impurities, and a requirement of a purification by a column chromatography so as to go against an industrial production. According to the present invention, problems of the prior art are solved. In addition, the preparation method provided by the present invention is mild, and avoids using solvents with high toxicity so as to comply with environmental requirements of the industrial production.

The present invention provides the preparation of olmesartan medoxomil containing less than about 0.1% of one or more of the impurities OLM-Me, OLM-Cl, and OLM-eliminate.

The present invention relates to an improved process for the manufacture of olmesartan and pharmaceutically acceptable salts and esters thereof as an active ingredient of a medicament for the treatment of hypertension and related diseases and conditions.

A process for purifying olmesartan medoxomil is provided comprising (a) dissolving olmesartan medoxomil in a solvent system comprising a ketone and at least one solvent selected from the group consisting of an alcohol-containing solvent, an ester-containing solvent and mixtures thereof to obtain a solution; and (b) recovering substantially pure olmesartan medoxomil. Also disclosed is substantially pure olmesartan medoxomil and pharmaceutical compositions containing same.

The present invention relates to a process for the preparation and purification of trityl olmesartan medoxomil and olmesartan medoxomil.

The invention provides a pharmaceutical composition which comprises calcium channel blockers of a medicinal dose, angiotensin II receptor antagonists of a medicinal dose, one or more of B vitamins of a medicinal dose and pharmaceutically acceptable carriers, wherein the calcium channel blockers are selected from amlodipine, felodipine, israbipine, nicardipine, nifedipine, nisoldipine, nitrendipine, lacidipine, diltiazem or verapamil; the angiotensin II receptor antagonists are selected from candesartan, telmisartan, losartan, valsartan, irbesartan, eprosartan, tasosartan or olmesartan; and the B vitamins are selected from one or more of vitamin B6, vitamin B12, folic acid and calcium leucovorin. The pharmaceutical composition of the invention can improve the curative effect of the hypotensor, enhance the target organ protecting action of the hypotensor, and reduce the morbidity of complications of angina, myocardial infarction and the like.

The invention discloses olmesartan medoxomil tablets and a preparation method thereof. The cores of 1000 olmesartan medoxomil tablets comprise 20g of olmesartan medoxomil, 60-95g of lactose (1), 30g of lactose (2), 45-50g of microcrystalline cellulose, 5g of polyvinylpyrrolidone K30 (PVPK30), 8g of low-substituted hydroxypropyl cellulose (L-HPC), 1g of magnesium stearate and an ethanol water solution for preparing a soft material. The invention solves the problem that no olmesartan medoxomil tablets can be used clinically at present.

The invention discloses a process for refining olmesartan medoxomil by adopting a mixed solution of acetone and water. The process comprises the steps that the olmesartan medoxomil is dissolved in the acetone or the mixed solution of the acetone and the water; then an obtained olmesartan medoxomil solution is added to hot water to be stirred and crystallized; and after the olmesartan medoxomil solution is filtered and dried, the olmesartan medoxomil is obtained. The process has the characteristics of good refining effect and high yield; and the acetone residual amount is small and can be controlled at about 1,000 ppm.

The invention relates to a medicament compound preparation formed by mixing olmesartan medoxomil with benzene sulfonic acid amlodipine and hydrochlorothiazide. Both the olmesartan medoxomil and amlodipine are unstable compounds, and are difficultly prepared into mixed medicaments with stable active ingredients. According to the invention, the adjuvant of the olmesartan medoxomil and amlodipine compound preparation is regulated, so that the amounts of degradation products and impurities of the olmesartan medoxomil are effectively reduced. The invention provides a method for preparing the fixed-dose compound preparation which takes the olmesartan medoxomil, the amlodipine and hydrochlorothiazide as the active ingredients.

The invention provides a new olmesartan medoxomil crystal and a preparation method thereof; the crystal has good crystallinity and stability; the preparation method is realized by recrystallization of olmesartan medoxomil in a mixed solvent. The olmesartan medoxomil crystal prepared by the method has good crystallinity and stability; the method is simple; the used organic solvent is a Class III solvent, which has low toxicity, and is beneficial to environmental protection; and the method is suitable for large-scale production.

The invention relates to the field of medicines, and particularly relates to an olmesartan medoxomil tablet and a preparation method thereof. Tablet cores of every 1,000 pieces of olmesartan medoxomil tablets consist of the following raw materials according to the weight: 18-22 g of olmesartan medoxomil, 80-120 g of lactose, 30-45 g of microcrystalline cellulose, 30-50 g of low substituted hydroxypropy cellulose, 8-12 g of polylactic acid and 0.5-1.5 g of magnesium stearate. After being tabletted, the components are wrapped by thin film coats; thin film coat liquid is prepared from the following materials: 20 g of opadry and 5 g of polylactic acid and is prepared by dissolving the raw materials in 200 g of ethyl alcohol with the concentration of 80 percent for uniform mixing.

A 4,6-dihydrofurano[3,4-d] imidazole-6-ketone derivative, its pharmacological receptible salt, and the preparing process of said derivatives are disclosed. Said compound can be used as the intermediate for synthesizing the antagon of angiotensin II receptor.

The invention relates to a preparation method of a compound tablet prepared from levamlodipine and olmesartan medoxomil as well as auxiliary materials. The preparation method is characterized in that the compound tablet is prepared by adopting a mode of non-wet granulation and has better quality and stability.

The invention relates to a method for preparing and purifying an olmesartan intermediate. The preparation method comprises the following steps of: chlorinating 4,5-dimethyl-1,3-dioxa-cyclopentene-2-ketone, distilling under reduced pressure to obtain 4-chloro-4-methyl-5-methylene-1,3-dioxolane-2-ketone, and performing rearrangement reaction to generate the olmesartan intermediate; reducing the temperature to be below 50 DEG C, concentrating until a solvent is removed completely to obtain a crude product; and recrystallizing and purifying the crude product at the temperature of between -20 and 0 DEG C for 1 to 48 hours, wherein a recrystallization solvent may be one or a mixed solvent of more of an alkane solvent and an ether solvent. The preparation method is low in production cost, mild in reaction condition and easy to operate, raw materials are wide in sources, and high-content 4-chloromethyl-5-methyl-1,3-dioxa-cyclopentene-2-ketone can be obtained directly, so the method is particularly suitable for large-scale industrial production.

The invention discloses an olmesartan liposome solid preparation prepared by the following raw and supplementary material components in parts by weight: 1 part of olmesartan, 2.5-14 parts of dioleoyl-phosphatidylcholine, 0.5-6 parts of cholesterol, 0.8-10 parts of sodium glycyl-cholate, 0.2-5 parts of soy sterol and 2-20 parts of pharmaceutically acceptable carriers or excipients. The liposome solid preparation provided by the invention has high entrapment rate, even grain size, long medicament retention time in blood circulation, simple equipment, easiness in operation, improved product quality of the preparation and lessened toxic and side effects and is suitable for industrial production.

The present invention provides the preparation of olmesartan medoxomil containing less than about 0.1% of one or more of the impurities OLM-Me, OLM-Cl, and OLM-eliminate.

The present invention provides a process for the preparation of Olmesartan medoxomil] by condensing the ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate with 4-[2-(trityl tetrazol-5-yl)phenyl]benzyl bromide to obtain ethyl 4-(1-hydroxy-1-methyl ethyl)-2-propyl-1-{4-[2-(trityl tetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carboxylate and then hydrolyzing ethyl 4-(1-hydroxy-1-methyl ethyl)-2-propyl-1-{4-[2-(trityl tetrazol-5-yl)phenyl]phenyl}methyl imidazole-5-carboxylate to obtain trityl Olmesartan dihydrate followed by reacting trityl Olmesartan dihydrate with 4-chloromethyl-5-methyl-2-oxo-1,3-dioxolene to obtain trityl Olmesartan medoxomil and then deprotecting trityl Olmesartan medoxomil to obtain Olmesartan medoxomil.

The invention provides a preparation method of ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazolyl-5-carboxylate (1). The method accurately controls the reaction material ratio, solvent composition, solvent consumption, reaction temperature, reaction time and other technological parameters, and obviously lowers the content of the impurity compound disclosed as Formula 3, thereby obtaining the high-purity olmesartan medoxomil. The invention also provides application of the compound disclosed as Formula 3 as a quality control standard substance in preparing the ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazolyl-5-carboxylate (1).

The present invention provides a an angiotensin receptor antagonist and creatine phosphate sodium complex and uses thereof, wherein the complex comprises an angiotensin receptor antagonist and creatine phosphate sodium, a molar ratio of the angiotensin receptor antagonist to the creatine phosphate sodium is 1:1-2, and the angiotensin receptor antagonist is selected from valsartan, losartan, irbesartan, telmisartan, eprosartan, candesartan, olmesartan, saprisartan, tasosartan, and elisartan. According to the present invention, the complex is formed by compounding the angiotensin receptor antagonist and the creatine phosphate sodium, and provides the unexpected double effect and the synergistic effect for treatment of heart failure and high blood pressure, the cocrystallization salt hydrate formed by linking the hydrogen bond has the stable characteristic, the pharmacokinetic property is significantly provided, and the positive application prospects are provided in the fields of anti-high blood pressure treatment and anti-heart failure treatment.

The invention relates to a stable solid dosage form comprising olmesartan medoxomil and amlodipine or a pharmacologically acceptable salt thereof. In particular, it relates to solid dosage forms free from reducing sugars. The stable solid dosage form may optionally further comprise hydrochlorothiazide or a pharmacologically acceptable salt thereof.

The invention relates to an Olmesartan medoxomil tablet and preparation technology thereof. The core of the Olmesartan medoxomil tablet is prepared by directly pressing Olmesartan medoxomil and medicinal assistants, and the particle size of a position accumulating 90% of Olmesartan medoxomil is 1-100[mu]m; and the medicinal assistants comprise a filler, a disintegrating agent and a lubricant, wherein the lubricant is one or more of neutral or inert lubricants. Raw materials of the core of the tablet comprise, by weight, 20 parts of Olmesartan medoxomil, 80-180 parts of the filler, 10-20 parts of the disintegrating agent and 2-10 parts of the lubricant. The Olmesartan medoxomil is crushed in an airflow crushing mode, the particle size is controlled, and the preparation technology adopts a direct powder pressing method, so the introduction of water in a wet granulation process and the degradation of active substances in a wet particle drying process are avoided, and the incidence of a hydrolysis reaction is prevented. The Olmesartan medoxomil tablet has the advantages of stability, good dissolution and simple preparation.

The invention discloses a tablet containing olmesartan medoxomil and amlodipine. The tablet is prepared from amlodipine besylate solid dispersion, olmesartan medoxomil and pharmaceutic adjuvants, wherein the amlodipine besylate solid dispersion consists of amlodipine besylate and hydroxypropyl methyl cellulose according to the weight rate of 1: (7-12). The amlodipine besylate in the compound tablets can be rapidly dissolved out and absorbed by organisms; and after orally taken by hypertensive, the olmesartan medoxomil and amlodipine-containing tablet plays the roles of enhancing the synergistic hypotensive effect of two active ingredients and remarkably reducing the adverse drug reaction.

The invention discloses a preparation method of olmesartan medoxomil and relates to the technical field of medicine. The method comprises the following steps: using 4-(1-hydroxy-1-methylethyl)-2-propylimidazol-5-ethylcarboxylate and N-(triphenylmethyl)-5-(4'-bromomethyl diphenyl-2-yl)tetrazole as raw materials, adopting a one-pot method to directly obtain 1-[[[27-(triphenylmethyl)-2H-tetrazole-5-yl]dipheny-4-yl]methyl]-2-propyl-4-(1-hydroxy-1-methylethyl)imidazol-5-carboxylic acid (5-methyl-2-oxo-1,3-dioxycyclopentene-4-yl)methyl ester. Compared with the prior art, the preparation method has the characteristics of simple preparation technology, high yield, low cost and the like, and the method is more beneficial to implementation of large-scale industrial production.

The invention discloses a preparation method of olmesartan medoxomil,Which is characterized by reacting ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate (I) and N-(triphenylmethyl)-5-(4'-bromoethylbiphenyl-2-)tetrazole (II) by a one-pot process to directly obtain lithium 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(triphenylmethyltetrazolyl-5-yl)phenyl]phenyl}methylimidazol-5-carboxylate (IV). The invention has the advantages of mild reaction conditions, fewer byproducts, high purity of the end product, high total yield, high safety and environmental protection, and is suitable for industrial production; and by using the one-pot process, the invention is simpler to operate, saves the time and lowers the cost.

The invention discloses a tablet containing olmesartan medoxomil and a preparation method of the tablet. The tablet is composed of olmesartan medoxomil, a disintegrating agent, a filling agent, a diluent, an anti-sticking agent and a lubricating agent. The preparation method disclosed by the invention comprises the following steps: performing jet milling treatment on olmesartan medoxomil, and mixing with the anti-sticking agent to pass through a 30-mesh sieve; mixing with other medicinal auxiliary materials, and directly tabletting; performing film coating on the tablet core after tabletting,wherein the film coating premixed agent is composed of the following materials: hydroxypropyl methylcellulose, titanium dioxide and polyethylene glycol. The olmesartan medoxomil tablet provided by theinvention is high in in-vitro dissolution rate, high in bioavailability, excellent in stability and mechanical strength, less in odor, sticking-free and suitable for large-scale mass production.

[Object]The present invention provides an olmesartan medoxomil-containing drug product having an improved dissolution property.[Means for Solution]A production method for an olmesartan medoxomil-containing drug product characterized in that the method comprises a process of compressing a composition.

The invention provides a novel medical composition used for treating hypertension and more particularly relate to levamlodipine and olmesartan medoxomil, wherein, the weight ratio of the levamlodipine to the olmesartan medoxomil is 1 to (1-20). The levamlodipine disclosed by the invention comprises salts accepatable in pharmacy, such as benzene sulfonate, maleate and other salts. The medical composition provided by the invention has the advantages of obvious therapeutic effect, convenient usage and low cost.