40 results about "Azilsartan Medoxomil" patented technology

The invention relates to an azilsartan medoxomil compound, a preparation method and a medicinal composition thereof, and belongs to the technical field of medicine. The azilsartan medoxomil compound is (5-methyl-2-oxo-1,3-m-dioxole-4-group) methyl-2-ethoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazole-3-group) biphenyl-4-group] methyl}-1H-benzimidazole-7-carboxylate sylvite monohydrate. The invention also relates to the preparation method of the compound and the medicinal composition using the compound as an active substance. Compared with an azilsartan medoxomil sylvite, the compound has the advantages of better stability, suitability for preparing medicinal preparations of various forms and suitability for storage and use.

The present invention relates to process an improved process for the preparation of azilsartan medoxomil. In particular, the field of invention relates to a process for purification of azilsartan medoxomil. More particularly, the invention relates to an improved process for preparation of azilsartan medoxomil and its pharmaceutically acceptable salts.

The invention relates to a synthesis method of an azilsartan intermediate compound 2-ethoxyl-1-[[2'-(hydroxyl amidino)-biphenylyl]-4-yl]methyl-1H-benzimidazole-7-carboxylic acid and ester derivatives thereof. According to the method, 2-ethoxyl-1-[[2'-cyano-biphenylyl]-4-yl]methyl-1H-benzimidazole-7-carboxylic acid and esters thereof used as the raw materials react with hydroxylamine hydrochloride aqueous solution under the weak base condition with ethanol as the solvent. The method disclosed by the invention has the advantages of less side reaction, unnecessary purification of the product obtained according to the method and suitability for industrial production; and the method can be used for preparing high-purity azilsartan and azilsartan medoxomil.

The present invention relates to the field of pharmaceutical chemistry. Disclosed herein is a crystalline form of azilsartan medoxomil potassium, which is substantially pure. The crystalline form is crystalline form A, form B, form C, form D, form E, form F, form G, form H, form I, form J, form K or form L. The substantially pure crystalline forms of azilsartan medoxomil potassium of the invention generally have good properties such as high solubility, high bioavailability, good stability, long shelf life and good antistatic property. The crystalline forms of azilsartan medoxomil potassium generally exhibit an excellent performance in reducing clinical systolic blood pressure (SBP) and average 24-hour SBP. Disclosed herein are methods of preparing the substantially pure crystalline forms of azilsartan medoxomil potassium, pharmaceutical compositions comprising the crystalline forms, and preparation methods and uses thereof.

The invention provides three kinds of azilsartan medoxomil intermediates and synthetic methods thereof. The azilsartan medoxomil intermediates are as shown in formulae 8, 9 and 11, and prepared according to the scheme as shown in the specification. The invention also provides a synthetic method of azilsartan medoxomil, wherein the synthetic method is as shown in the specification. The invention provides three types of azilsartan medoxomil intermediates, and expands the research field of important azilsartan medoxomil intermediates; a compound shown in the formula 11 is adopted and subjected to hydrolysis, condensation and deprotection so as to obtain a final product azilsartan medoxomil; compared with the prior art, the synthetic method has the advantages that the utilization of expensive 4-hydroxymethyl-5-methyl-1,3-dioxo hetercyclopentene-2-ketone is avoided, so that the production cost can be greatly reduced; in the production process of the azilsartan medoxomil intermediates disclosed by the invention, the purity of the intermediates can achieve over 98%, and can meet market demands, and the yields of the compound as shown in the formula 11 to a final product azilsartan medoxomil are high, and is up to 68-75%; the purity of obtained final products azilsartan medoxomil reaches 99.0-99.5%.

The present invention relates to an azilsartan medoxomil synthesis method, wherein 4'-bromomethyl-2-biphenylcarbonitrile is adopted as a raw material, a hydroxylamine reaction is performed, cyclization is performed to prepare a compound II, 2-ethoxy benzimidazole-7-carboxylic acid is adopted as a raw material, an esterification reaction is performed to obtain a compound V, and the compound II reacts with the compound V to prepare the azilsartan medoxomil. According to the present invention, the method has characteristics of short synthesis route, easy operation, high yield, 4'-bromomethyl-2-biphenylcarbonitrile consumption reducing, and cost reducing. The compounds I, II and IV are defined in the specification.

The invention discloses a preparation method of azilsartan. The method comprises the following steps: introducing an organic solvent solution of a compound 2 and carbon dioxide gas into a micro reactor, mixing and reacting at the temperature of 90 to 120 DEG C under the pressure of 0.8 to 1.2Mpa for 48 to 480 seconds to obtain azilsartan medoxomil, and discharging the azilsartan medoxomil out of the micro reactor; then, performing alkaline hydrolysis to obtain the azilsartan. A synthetic method disclosed by the invention has the advantages of use of readily-available raw materials, easiness in operation, less reaction side products in each step, high yield, extremely high purity of an obtained product, easiness in separating and purifying reaction products in each step, and suitability for industrial production. The structure of the azilsartan is shown in the description.

The invention relates to an azilsartan medoxomil capsule and a preparation method thereof. The capsule is prepared from raw materials in parts by mass as follows: 10-30 parts of azilsartan medoxomil, 30-70 parts of lactose, 20-50 parts of microcrystalline cellulose, 5-15 parts of crospovidone, 1-3 parts of magnesium stearate and 1-3 parts of silicon dioxide. According to the azilsartan medoxomil capsule and the preparation method thereof, pharmaceutical composition for treating hypertension is reasonably proportioned, can rapidly release medicine and can realize a good curative effect on symptoms of diseases.

The invention provides a method for detecting the impurity content of 4-chloro-4-methyl-5-methylene-1, 3-dioxolane-2-ketone in a sample by adopting a gas chromatography-mass spectrometry method, the sample is olmesartan medoxomil, azilsartan, azilsartan medoxomil, azilsartan medoxomil potassium, lenampicillin and prulifloxacin, the sample does not need to be specially treated, and no matrix influence exists. Chromatographic conditions adopted by the detection method are as follows: a chromatographic column is a capillary column taking (14%-cyanopropyl-phenyl)-methylpolysiloxane as a stationary liquid, and temperature programming is adopted; the temperature programming is as follows: the initial column temperature is 150 DEG C, and the temperature is kept for 1 minute; the temperature raises to 200 DEG C at the speed of 35 DEG C per minute, and the temperature is kept for 5 minutes; and the temperature raises to 250 DEG C at the speed of 30 DEG C per minute, and the temperature is kept for 3 minutes.

The present invention relates to the field of pharmaceutical chemistry. Disclosed herein is a crystalline form of azilsartan medoxomil potassium, which is substantially pure. The crystalline form is crystalline form A, form B, form C, form D, form E, form F, form G, form H, form I, form J, form K or form L. The substantially pure crystalline forms of azilsartan medoxomil potassium of the invention generally have good properties such as high solubility, high bioavailability, good stability, long shelf life and good antistatic property. The crystalline forms of azilsartan medoxomil potassium generally exhibit an excellent performance in reducing clinical systolic blood pressure (SBP) and average 24-hour SBP. Disclosed herein are methods of preparing the substantially pure crystalline forms of azilsartan medoxomil potassium, pharmaceutical compositions comprising the crystalline forms, and preparation methods and uses thereof.

The invention relates to a crystal form of azilsartan medoxomil and a preparation method of the crystal form, in particular to multiple novel crystal forms of a compound 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazole-3-base)[1,1'-biphenyl]-4-base]methyl]-2-ethoxy-1H-benzimidazole-7-carboxylic acid(5-methyl-2-oxo-1,3-dioxole-4-yl)methyl ester and a preparation method of the novel crystal forms. Compared with the prior art, water solubility of the novel crystal forms is high, the melting point is low, therefore, compared with an existing crystal form, good dissolubility and bioavailability are achieved, and a pharmaceutic preparation can be obtained more conveniently through a hot-melt extrusion method.

The invention relates to the field of medicines and in particular relates to a synthesis method for azilsartan medoxomil or salt thereof, an intermediate of the azilsartan medoxomil or the salt thereof and a synthesis method for the intermediate. According to the novel method for the azilsartan medoxomil or the salt thereof, the problems of low synthesized azilsartan medoxomil yield and large number of byproducts are solved. Furthermore, the invention further provides a synthesis intermediate of the azilsartan medoxomil or the salt thereof and two preparation methods. In a synthesis process, an alcohol fragment of the azilsartan medoxomil is introduced at first, so that a part of the azilsartan medoxomil is formed, and a cyclization structure fragment is synthesized; therefore, the problem that the yield is reduced because of side reaction caused by active hydrogen in a carbonyldimidazole structure of an azilsartan acid structure is solved in a reaction process; the reaction yield is greatly improved, so that a finished product is easier to purify; the synthesis method is particularly suitable for industrial production.

The invention relates to an azilsartan medoxomil compound, a preparation method and a medicinal composition thereof, and belongs to the technical field of medicine. The azilsartan medoxomil compound is (5-methyl-2-oxo-1,3-m-dioxole-4-group) methyl-2-ethoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazole-3-group) biphenyl-4-group] methyl}-1H-benzimidazole-7-carboxylate sylvite monohydrate. The invention also relates to the preparation method of the compound and the medicinal composition using the compound as an active substance. Compared with an azilsartan medoxomil sylvite, the compound has the advantages of better stability, suitability for preparing medicinal preparations of various forms and suitability for storage and use.