39 results about "Candesartan cilexitil" patented technology

The present invention is directed to compositions comprising a candesartan, such as candesartan cilexitil. The candesartan particles of the composition have an effective average particle size of less than about 2000 nm. The candesartan compositions of the invention are useful in the treatment of hypertension or related cardiovascular conditions.

The present invention provides an improved synthesis for the manufacture of candesartan and pharmaceutically acceptable salts and esters thereof as active ingredients of a medicament for the treatment of hypertension and related diseases and conditions which comprises the removal of the tetrazolyl protecting group in an organic solvent, and in the presence of a Lewis acid.

The invention discloses an oral candesartan cilexetil solid preparation and a preparation method thereof. The oral solid preparation is prepared from candesartan cilexetil, stabilizer and pharmaceutically acceptable auxiliary ingredients, wherein the stabilizer is beta-cyclodextrin, and the weight of the stabilizer is 0.3 to 3 times that of the candesartan cilexetil. The preparation method comprises the steps of mixing candesartan cilexetil, beta-cyclodextrin or derivatives thereof and red iron oxide and sieving twice with a 100-mesh sieve, and then adding proper pharmaceutical auxiliary ingredients to obtain the candesartan cilexetil preparation. According to the oral candesartan cilexetil solid preparation and the preparation method thereof, the candesartan cilexetil can be inhibited from decomposing and keep long-time stabilizing and the expiry date of the candesartan cilexetil preparation can be prolonged.

The invention relates to a continuous-flow production process for synthesizing a candesartan cilexetil intermediate, belonging to the technical field of fine chemical engineering. The invention particularly relates to a process for continuously preparing 2-((tert-butoxycarbonyl)amino)-3-nitrobenzoate by using a microchannel reactor. The process comprises the following steps: carrying out staying reaction on 2-(chlorocarbonyl)-3-nitrobenzoate and sodium azide in a first reaction module; then allowing reaction liquid and water to simultaneously enter a continuous separator for separation; and subjecting an organic layer obtained through separation to reacting with tert-butyl alcohol in a second reaction module to obtain a target product. The method provided by the invention is safe, simple to operate, efficient and easy for large-scale production.

The invention relates to a candesartan cilexetil self-microemulsion soft capsule and a preparation method thereof. The soft capsule comprises capsule liquid and content medicine liquid. The preparation method is as follows: 100-130 parts of gelatin is arranged in mixing solution for swelling, wherein the mixing solution is formed by 18-30 parts of glycerol, 20-30 parts of sorbic alcohol and 100-120 parts of water; then 0.1-0.3 part of ethylparaben is added, heating is carried out until the gelatin is dissolved, the mixture is stirred uniformly and is filtered, and vacuum defoaming and heat insulation are carried out, thus obtaining the capsule liquid; 1-2 parts of candesartan cilexetil, 20-40 parts of assistant emulsifiers, 10-30 parts of oil phase and 80-100 parts of emulsifiers are mixed uniformly, and then the mixture is heated and stirred until the uniform and transparent content solution is formed; and the prepared capsule liquid and the prepared content solution the weight percentage ratio of which is 4:3 are moulded and pressed into soft capsules by rotating a mould press, and then drying and surface treatment are carried out on the soft capsules, thus obtaining the finished products. In the invention, the bioavailability of the candesartan cilexetil is improved, and the preparation method is simple relatively, the production is easy, thus the application prospect is wide.

The invention provides a method for preparing candesartan cilexetil, which can solve the problems of longer reaction route, easy remaining of toxic substances in medicines and lower total yield existing in the prior art. In the method, the candesartan cilexetil is finally prepared by using 2-amino-3-nitrobenzoic acid as an initial raw material through esterification reaction, N-alkylation reaction, nitro reduction reaction, cyclization reaction, hydrolysis reaction, esterification reaction and tetrazole protecting group deprotection reaction. The synthetic method has simple steps and high yield, greatly reduces the participation and generation of toxic products in the reaction process, reduces the release of waste and is beneficial to clean production.

The invention relates to a method for analyzing the genotoxic impurity 1-chloroethylcyclohexyl carbonate of candesartan cilexetil, belonging to the technical field of crude drug analysis. The present invention utilizes the impurity 1-chloroethyl cyclohexyl carbonate existing in candesartan cilexetil and the pre-column derivation method of the derivation reaction with candesartan cilexetil itself to measure the impurity 1-chloroethyl cyclohexyl carbonate content, to achieve the control of genotoxic impurity 1-chloroethyl cyclohexyl carbonate in candesartan cilexetil. The invention provides a detection method for the genotoxic impurity in candesartan cilexetil, which provides guarantee for the quality control of candesartan cilexetil preparations.

The invention discloses a brand-new oral solid pharmaceutical composition. The pharmaceutical composition is an oral preparation prepared from hydrochlorothiazide, levamlodipine, candesartan cilexetil and pharmaceutically acceptable auxiliary materials. The oral preparations include but are not limited to tablets or capsules. The composition contains the following raw materials in parts by weight: 5-25 parts by weight of hydrochlorothiazide, 2.5-5 parts by weight of levamlodipine, 4-20 parts by weight of candesartan cilexetil, and 30-60 parts by weight of microcrystalline cellulose 30-60 parts by weight of compressible starch, 30-50 parts by weight of cross-linked polyvinylpyrrolidone, 1-2 parts by weight of silicon dioxide and 0.5-2 parts by weight of magnesium stearate. The medicinal composition of the invention has scientific and reasonable prescription, low auxiliary material content and high bioavailability, and is the first choice medicine for treating hypertension.

The preparation method of candesartan cilexetil and its precursor compound. The precursor compound is 2-ethoxy-1-[[2′-(1-R-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-1H -Benzimidazole-7-carboxylic acid 1-(cyclohexyloxycarbonyloxy)ethyl ester (III), from 2-ethoxy-1-(4'-halophenyl)methyl-1H-benzene Imidazole-7-carboxylic acid 1-[[(cyclohexyloxy)carbonyl]oxy]ethyl ester (I) and 2-(1-R-1H-tetrazol-5-yl)phenylboronic acid or 2- (1-R-1H-tetrazol-5-yl) phenyl borate (II) reacts in a soluble organic reaction medium and in the presence of a catalyst and a water-soluble basic compound allowed by the Suzuki reaction get. The precursor compound can be further hydrolyzed under acidic conditions to obtain candesartan cilexetil which can be used as medicine. The method can conveniently and advantageously prepare the candesartan cilexetil compound.

The invention discloses a nephropathy treating or preventing effect enhancer of candesartan cilexetil and other renin-angiotensin system inhibitors. The enhancer contains specific prostaglandin I derivatives such as bereprosodium as active ingredients.

The invention discloses a hydrochlorothiazide crystal and a candesartan cilexetil hydrochlorothiazide medicinal combination thereof. The characteristic peaks of the hydrochlorothiazide crystal in an X-ray powder diffraction pattern, which are measured and obtained by using a Cu-K[alpha] ray, are displayed when 2[theta] is 4.1 degrees, 8.2 degrees, 9.8 degrees, 12.1 degrees, 15.1 degrees, 16.7 degrees, 19.3 degrees, 20.0 degrees, 22.1 degrees, 23.3 degrees and 26.8 degrees. The combination comprises 4-20 parts of candesartan cilexetil, 10-15 parts of the hydrochlorothiazide crystal, 10-50 parts of pregelatinized starch, 15-35 parts of microcrystalline cellulose PH102, 10-45 parts of crosslinked polyvinylpyrrolidone and 0.5-1 part of magnesium stearate. The medicinal combination has a reasonable prescription, stable and reliable quality, and better disintegration time limit and dissolution rate; a direct powder tabletting process is adopted; the process is simple; the production period is short; the production cost is low; and the industrialized production is facilitated.

The invention relates to the technical field of chemical drug analysis, in particular to a method for detecting azide compounds in candesartan cilexetil. The detection method of the present invention is to take candesartan cilexetil raw material drug to be tested, add acetonitrile for ultrasonic dissolution, and then dilute with sulfuric acid aqueous solution; the volume ratio of the acetonitrile and sulfuric acid water is 40:60~60:40; after fully shaking Filtrate, get the filtrate and stand-by as need testing solution; Chromatographic column uses octadecylsilane bonded silica gel as stationary phase, adopts acetonitrile-sulfuric acid aqueous solution as mobile phase A, acetonitrile-water as mobile phase B to carry out gradient elution, carry out HPLC detection, record spectrum. The detection method of the invention can quickly and conveniently separate and quantitatively determine the sodium azide in the candesartan cilexetil, thereby effectively controlling the quality of the candesartan cilexetil product.

The invention relates to a brand new drug composition containing levamlodipine besylate and candesartan cilexetil and a preparation method thereof. The composition comprises the active ingredients such as levamlodipine besylate and candesartan cilexetil and pharmaceutically acceptable auxiliaries, wherein levamlodipine besylate is levamlodipine besylate crystals; and the characteristic peak in the X-ray powder diffraction pattern obtained after measuring the crystals with a Cu-Kalpha ray is displayed at 2theta, namely 8.0 degrees, 12.1 degrees, 15.4 degrees, 17.0 degrees, 19.8 degrees, 21.6 degrees, 23.0 degrees, 24.3 degrees, 25.7 degrees, 27.4 degrees, 30.7 degrees and 33.5 degrees. The drug composition and the preparation method have the following advantages: the crystals can improve the solubility of levamlodipine besylate to some extent, thus amlodipine besylate in the drug composition is dissolved out more quickly and the drug composition has a better curative effect and good stability; and the method adopts a direct powder compression technology, has the advantages of simple technology, short production period and low production cost and is easy to realize industrial production.