34 results about "BENIDIPINE HYDROCHLORIDE" patented technology

The invention discloses a synthesis process of N-benzyl-3-piperidinol which is the most important midbody for synthesizing Benidipine. The synthesis process comprises the following steps of: taking 3-hydroxy pyridine as a raw material, firstly performing the reaction with benzyl chloride to generate quaternary ammonium salt of N-benzyl-3-hydroxy pyridine, then carrying out catalytic reduction on the quaternary ammonium salt under the moderate hydrogen pressure (3 to 5atm) by using a nickel-based catalyst which is low in cost and easy to be prepared so as to obtain the N-benzyl-3-piperidinol. The invention also discloses a formula and a preparation method of the nickel-based catalyst used in the synthesis process of the N-benzyl-3-piperidinol. The invention has the advantages of low cost, safe operation, high product purity, and the like and is a synthesis route of the N-benzyl-3-piperidinol which is environment-friendly and suitable for industrial production.

The object of the present invention is to provide a pharmaceutical composition of benidipine hydrochloride having a rapid precipitation property for promoting the rapid absorption of benidipine hydrochloride as the main component, which is characterized in that it contains a volume average particle diameter of 1.0 to 50.0 μm. Benidipine hydrochloride crystals or powders with a volume average particle diameter of 1.0-50.0 μm, wherein the powders contain benidipine hydrochloride crystals and water-soluble or hydrophilic functional additives.

The present invention relates to nanoparticles of benidipine hydrochloride (+ / -)-(R*)-1, 4-dihydro-2, 6-dimethyl-4-(m-nitrophenyl)-3, 5-picolinic acid methyl ester [(R*)-1-benzyl-3-piperidine alcohol ester] hydrochloride and an ultrasonic preparation method thereof.

A method and composition are provided for the treatment of an anorectal disorder and for controlling the pain associated therewith. The method comprises administering to a subject in need of such treatment therapeutically effective amounts of a calcium channel blocker either alone or together with a nitric oxide donor. Amlodipine, anipamil, barnidipine, benidipine, bepridil, darodipine, diltiazem, efonidipine, felodipine, isradipine, lacidipine, lercanidipine, lidoflazine, manidipine, mepirodipine, nicardipine, nifedipine, niludipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, perhexiline, tiapamil, verapamil and pharmaceutically acceptable salts thereof, are suitable calcium channel blockers.

The invention discloses a synthetic method for a benidipine hydrochloride intermediate. The synthetic method comprises performing a nucleophilic substitution reaction on 3-hydroxypyridine and a benzyl halide under a solvent refluxing condition, so as to generate 1-benzyl-3-hydroxypyridiniumhalide; taking an alcohol as a solvent and reducing 1-benzyl-3-hydroxypyridiniumhalide to generate 1-benzyl-3-piperidinol; then performing transesterification reaction on 1-benzyl-3-piperidinol and ethyl acetoacetate under a refluxing condition by taking toluene as a solvent in the presence / absence of a catalyst, and under the condition that less than 30% of the alcohol is left, performing normal-pressure distillation until the alcohol completely finishes reaction, so as to obtain the product. The synthetic method is simple and has the three-step total yield of 80% or more, and all employed materials are industrialized products and are cheap and easily obtained, and the quality is easily controlled.

The invention relates to a preparation method of benidipine hydrochloride. The preparation method comprises the synthesis steps of: the synthesis of mixed anhydrides: adding one equivalent of 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-5-methyl carboxylate-3-carboxylic acid to an organic solvent, adding 1.1-1.4 equivalents of chlorophosphite under an alkaline condition, and reacting at a temperature ranging from 20 to 30 DEG C for 1-2 hours to form a reaction liquid containing the mixed anhydrides; the synthesis of benidipine: adding 0.9-1.1 equivalents of N-benzyl-3-hydroxypiperidine to the reaction liquid of the mixed anhydrides, stirring at a temperature ranging from 20 to 30 DEG C for 5-15 minutes and refluxing for 4-6 hours to obtain the a reaction liquid containing the benidipine. The preparation method of the benidipine hydrochloride provided by the invention is simple to operate, high and stable in reaction yield, mild in reaction conditions, free of potential safety hazards, easy to purify and high in purity, and also advantageous for industrial production.

The invention relates to a water treatment agent for removing nitrobenzene compounds in water. The water treatment agent is compounded by 6,6,10-trimethyl bicyclo-3,1,1-heptyl-2-ene, 3-phenyl-2-propylester, rabeprazole sodium, ferric ammonium oxalate, alpha-copaene, dipyrazolone, buflomedil, 2-(4-methyl-3-cyclohexenyl)-2-propanol, ferric chloride, asiaticoside, silymarin, 3-nonylene-2-ketone, polyacrylamide, gluconic acid lactone, benidipine hydrochloride and 2-hydroxyethyl cellulose. The water treatment agent has strong complexing capacity for the nitrobenzene compounds, the precipitation speed of complexes is high, the removal rate can reach 99%, toxicity is low, the dosage is low, no harm is caused to water, and treatment cost is low.

The invention relates to a preparation method of high-purity benidipine hydrochloride, and solves the technical problems. The preparation method comprises the following steps: reacting 2, 6-dimethyl-4-(m-nitrophenyl)-1, 4-dihydropyridine-5-carboxylic acid methyl ester-3-carboxylic acid with chlorophosphate under an alkaline condition to generate mixed anhydride; enabling the mixed acid anhydride to react with the N-benzyl-3-hydroxypiperidine to generate benidipine; cooling the reaction liquid containing benidipine to 40-50 DEG C, and decolorizing with activated carbon; dissolving the decolored benidipine crude product with dichloromethane, washing with a NaOH solution, water, hydrochloric acid and water in sequence, then drying, and spin-drying the solvent to obtain a benidipine hydrochloride crude product; and dissolving a benidipine hydrochloride crude product in a mixed solution of ethanol and acetone, refluxing, stirring, and separating out a benidipine hydrochloride pure product. The method can be widely applied to the field of medicine preparation.

The invention belongs to the field of chemical synthesis of drugs, and particularly relates to a preparation method of a hypotensive drug benidipine hydrochloride. The method comprises the following steps: carrying out a Knoevenagel reaction, a Michael addition reaction, cyclization and hydrolysis on starting raw materials 3-nitrobenzaldehyde and methyl acetoacetate in the presence of a catalyst, reacting with thionyl chloride, directly reacting with 1-benzyl-3-hydroxypiperidine, and refining to obtain the benidipine hydrochloride. The benidipine hydrochloride obtained by adopting the preparation method of the benidipine hydrochloride is high in purity, column chromatography isolation is not needed, and the HPLC purity of the product is 99.5% or above. The yield of the obtained benidipine hydrochloride is relatively high and can reach 68% or above.

The invention discloses a compound preparation containing benidipine hydrochloride and atorvastatin calcium and application for the compound preparation. The compound preparation comprises the following active ingredients: the benidipine hydrochloride and the atorvastatin calcium. By the compound preparation, the defect that hypertension and hyperlipidemia cannot be treated simultaneously by single medicines is overcome, and the compound preparation is prepared by compounding the benidipine hydrochloride and the atorvastatin calcium. The preparation can be prepared into oral formulations of different forms, and a treatment effect of the compound preparation is enhanced under the synergetic and complementary action of medicines, the using dose of the medicines is reduced in clinical application, and the adverse reaction of patients is relieved, so the compound preparation is accepted easily by the patients. The compound preparation has an obvious treatment effect on hypertension and hyperlipidemia, is suitable for the patients who suffer from serious cardiovascular cerebrovascular diseases accompanied with high cholesterol, blood fat metabolic disturbance, cardiac failure, atherosclerosis, coronary heart diseases, acute myocardial infarction and the like, and is low in cost, easy to prepare and convenient to popularize and apply.

The invention discloses a compound preparation containing benidipine hydrochloride and metoprolol tartrate and an application thereof; for the preparation, the benidipine hydrochloride and the metoprolol tartrate are taken as active pharmaceutical ingredients. The compound pressure-reducing preparation adopts drug combination and is good in efficacy, less in side effects and high in performance-price ratio; the compound preparation is taken once per day, the administration is convenient and the drug compliance of a patient can be improved. The preparation can be prepared into oral formulations in different forms, thereby realizing synergic and complementary action of drugs and enhancing the treatment effect of the compound preparation. The compound preparation has significant effects for treating hypertension and can also be used for treating angina pectoris, myocardial infarction and arrhythmia, as well as hypertrophic cardiomyopathy, aortic dissection, hyperthyroidism, cardiac neurosis, chronic stable heart failure and other symptoms. The compound preparation is low in price, simple to prepare and convenient to popularize and apply.

The invention relates to the field of medicine, and particularly provides application of benidipine in preparing a drug for preventing and / or treating infectious diseases caused by Bunya viruses. It is discovered for the first time that the benidipine and pharmaceutically acceptable derivatives thereof can be used for preventing or treating the infectious diseases caused by the Bunya viruses. Experimental results show that the benidipine has strong antiviral activity against the Bunya viruses, can significantly reduce the mortality and body weight change of mice infected by the Bunya viruses, shows a strong antiviral effect at the cell and animal levels, and has obvious technical advantages.

The invention provides a slow-release preparation of calcium antagonist and salt thereof and a preparation method thereof. The slow-release preparation comprises a slow-release phase which contains active pharmaceutical ingredients, the active pharmaceutical ingredients include 5-40mg of amlodipine or salt thereof calculated by amlodipine, 4-32mg of lacidipine or salt thereof calculated by lacidipine, 5-40mg of nisoldipine or salt thereof calculated by nisoldipine, 5-40mg of cilnidipine or salt thereof calculated by cilnidipine, 2-32mg of benidipine or salt thereof calculated by benidipine, 10-80mg of lercanidipine or salt thereof calculated by lercanidipine and 5-80mg of manidipine or salt thereof calculated by manidipine; in release media meeting sink conditions, higher than 90% of weight of the active pharmaceutical ingredients are released within a release period of 6-14h. The slow-release preparation is convenient to use, good in treatment effect, high in taking compliance, little in adverse reaction, quick in action, capable of maintaining stable and effective blood concentration for a long time, ingenious in design, simple in structure, high in stability and suitable for large-scale popularization and application.

The invention discloses a compound preparation containing benidipine hydrochloride and benazepril hydrochloride, as well as application thereof, wherein preparation containing benidipine hydrochloride and benazepril hydrochloride serve as effective components of the medicament. According to the compound preparation, the defects of large dose and high side effect of single drug are overcome, and the compound preparation disclosed by the invention is obtained by compounding the benidipine hydrochloride and benazepril hydrochloride. Oral preparations with different forms can be prepared by the preparation, due to synergic and complementary effects of medicaments, the compound preparation has reinforced treatment effect, the medicament dose is reduced in clinical application, adverse reaction of a patient is lightened, and the compound preparation can be accepted easily. The compound preparation has remarkable treatment effect in mild and severe hypertension, and is suitable for hypertension patient with cardiovascular remodeling, and patients with renal hypertension, hypertension with renal damage or with diabetic renal damage. Furthermore, the compound preparation has low price, simple preparation and easy popularization and application.

The invention relates to a method for measuring the content uniformity of a benidipine hydrochloride tablet, and solves the technical problems of poor discrimination, complex operation, long detection time and great influence on the health of personnel in the existing method for determining the content uniformity of the benidipine hydrochloride tablet. The method for measuring the content uniformity of the benidipine hydrochloride tablet comprises the following steps: taking one benidipine hydrochloride tablet, putting the benidipine hydrochloride tablet into a 100ml measuring flask, adding a proper amount of methanol-dilute phosphoric acid mixed solution, ultrasonically dissolving and diluting benidipine hydrochloride to a scale, uniformly shaking, filtering, and taking the subsequent filtrate as a test solution. The method is widely applied to detection of the content uniformity of the benidipine hydrochloride tablets.

The invention discloses a compound preparation containing benidipine hydrochloride and valsartan and an application thereof, wherein benidipine hydrochloride and valsartan are used as effective medicinal components of the preparation. Prepared by combination of drugs, the compound preparation for reducing pressure has good curative effects, less side effect and high cost performance, is taken once a day, is convenient to take, and can be used to raise drug compliance of patients. The preparation provided by the invention can be made into different oral dosage forms. Due to synergy and complementation of drugs, the treatment effect of the compound preparation is enhanced. The preparation provided by the invention has an obvious effect of treating hypertension and also can be applied to treat angina pectoris and protect kidney function. The preparation can be routinely used for patients with hypertension, myocardial infarction, heart failure, proteinuria, diabetes and the like, and is especially suitable for patients who are not tolerant to ACE inhibitor. The preparation is cheap, is simple to prepare, and is convenient for popularization and application.

The invention discloses a benidipine hydrochloride dispersing tablet, which comprises the following components in percentage by weight: 0.5-2% of benidipine hydrochloride used as an active ingredient as well as 40-62.8% of auxiliary material A, 35-55% of auxiliary material B, 1.0-5.0% of auxiliary material C, 0.5-6.0% of auxiliary material D and 0.2-5.0% of auxiliary material E used as a mixed auxiliary material. The method also discloses a preparation method of the benidipine hydrochloride dispersing tablet. The dispersing tablet disclosed by the invention has the advantages of short disintegration time, good dispersion state, rapid drug dissolution, definite curative effect, high bioavailability and convenience in administration, and can be administered by swallowing and can also be administered after being dispersed in water. The preparation process comprises production equipment and process for common tablets, and has the advantages of no need for special production process and equipment, simple production process and low cost.

The invention relates to a method for detecting methyl acetoacetate in benidipine hydrochloride, a high performance liquid chromatograph is used for detecting the content of methyl acetoacetate in benidipine hydrochloride, and a mobile phase used in the high performance liquid chromatograph comprises a mobile phase A and a mobile phase B, the mobile phase A is a mixed solution of a first phosphate solution with a pH value of 5-8 and methanol, and the mobile phase B is a mixed solution of a second phosphate solution with a pH value of 2-4 and methanol; the detection method comprises the following steps: enabling benidipine hydrochloride to enter a high performance liquid chromatograph, and respectively introducing a mobile phase A and a mobile phase B into the high performance liquid chromatograph to detect benidipine hydrochloride. The detection method provided by the invention can effectively detect the residual quantity of methyl acetoacetate in benidipine hydrochloride, and the detection method has good specificity, quantitation limit and detection limit, linearity and range, precision, accuracy and durability.

The invention provides an application of benidipine in preparation of a medicine for resisting novel coronavirus infectious diseases. According to the application, the fact that the benidipine can beused for preventing and treating the novel coronavirus infectious diseases is discovered for the first time, and the cytotoxicity of the benidipine hydrochloride on VeroE6 cells and the antiviral activity of the benidipine hydrochloride on COVID-19 viruses are detected, and it proves that the benidipine hydrochloride shows a relatively strong effect of resisting the COVID-19 viruses at a cellularlevel; and therefore, a new direction is provided for prevention and treatment of COVID-19 virus infectious diseases.

The invention discloses a compound preparation containing benidipine hydrochloride and atorvastatin calcium and application for the compound preparation. The compound preparation comprises the following active ingredients: the benidipine hydrochloride and the atorvastatin calcium. By the compound preparation, the defect that hypertension and hyperlipidemia cannot be treated simultaneously by single medicines is overcome, and the compound preparation is prepared by compounding the benidipine hydrochloride and the atorvastatin calcium. The preparation can be prepared into oral formulations of different forms, and a treatment effect of the compound preparation is enhanced under the synergetic and complementary action of medicines, the using dose of the medicines is reduced in clinical application, and the adverse reaction of patients is relieved, so the compound preparation is accepted easily by the patients. The compound preparation has an obvious treatment effect on hypertension and hyperlipidemia, is suitable for the patients who suffer from serious cardiovascular cerebrovascular diseases accompanied with high cholesterol, blood fat metabolic disturbance, cardiac failure, atherosclerosis, coronary heart diseases, acute myocardial infarction and the like, and is low in cost, easy to prepare and convenient to popularize and apply.

The invention discloses a compound preparation for treating hypertension. The compound preparation comprises 1-10 mg of benidipine and 5-50 mg of hydrochlorothiazide. The novel compound preparation provided by the invention solves the problem that when benidipine and hydrochlorothiazide are clinically used at present, side effects are obviously increased by increase of drug dose since only one of benidipine and hydrochlorothiazide is put into use. According to the novel compound preparation, benidipine and hydrochlorothiazide are used together to achieve synergetic and complementary curative effects; and the novel compound preparation increases the tolerance of patients, improves the compliance, is reduced in dose to relieve adverse reaction, and is convenient to take and low in price.

The invention provides a benidipine hydrochloride preparation and a preparation method thereof. The benidipine hydrochloride preparation of the present invention is composed of benidipine hydrochloride, an appropriate amount of surfactant and a solvent. After administration, the benidipine hydrochloride existing in a molecular state will dissolve rapidly and be quickly inhaled into the body, thereby achieving rapid onset of effect and improvement of The role of bioavailability. The preparation process of the benidipine hydrochloride preparation of the present invention is: dissolving benidipine hydrochloride and an appropriate amount of surfactant in a solvent by means of heating and stirring or ultrasonic probe, and filling in soft capsules or hard capsules after cooling .

The invention relates to a method for detecting impurities in a benidipine hydrochloride tablet, and solves the technical problem that no unified standard method exists in the impurity detection method in the benidipine hydrochloride tablet in China. The method for detecting impurities in the benidipine hydrochloride tablet comprises the following steps: preparing a test solution, namely respectively testing a system suitability solution prepared in step (3), a reference solution prepared in step (2) and the test solution prepared in step (1) by using high performance liquid chromatography. The method can be widely applied to the technical field of pharmacy.

The invention relates to a method for detecting the dissolution rate of a benidipine hydrochloride tablet. The method can better simulate the reflection environment and reflect the quality difference of samples. And the technical problems of low detection data result and large overall difference due to various adsorption and different degrees of decomposition of the benidipine hydrochloride in the existing detection method of the dissolution rate of the benidipine hydrochloride tablet are solved. The method for detecting the dissolution rate of the benidipine hydrochloride tablet comprises the following steps: taking the benidipine hydrochloride tablet, taking 900ml of hydrochloric acid solution of sodium chloride as a dissolution medium according to a dissolution rate determination method (four general rules 0931 second method of Chinese Pharmacopoeia 2015, using a settling basket), and operating according to the method at the rotating speed of 50 r / min; and taking a proper amount of the solution by using a sampling needle made of a PEEK material, centrifuging, and taking supernatant as a test solution. The method is applied to detection of the dissolution rate of the benidipine hydrochloride tablet.

The invention provides a benidipine hydrochloride solid preparation and a preparation method thereof. The benidipine hydrochloride solid preparation of the present invention consists of benidipine hydrochloride, a solid dispersion carrier and functional auxiliary materials. In the preparation, the highly dispersed benidipine hydrochloride has the characteristics of rapid dissolution and rapid absorption. The preparation process of the benidipine hydrochloride solid preparation of the present invention is: (1) adding benidipine hydrochloride to the molten solid dispersion carrier after being dissolved in a suitable organic solvent, or directly adding benidipine hydrochloride to the molten solid Stir in the dispersion carrier until the drug is dissolved, continue to maintain the molten state, stir until the organic solvent is evaporated, then rapidly cool, and pulverize; or dissolve benidipine hydrochloride and the solid dispersion carrier in a suitable organic solvent, and then evaporate the organic solvent, Pulverize; (2) The above-mentioned drug dispersion powder and functional auxiliary materials are prepared into granules through a certain granulation method, and the obtained granules are directly packaged as granules, and filled in capsules as capsules, and the obtained granules can also be compressed into tablets.

The invention relates to a method for detecting impurities in a benidipine hydrochloride bulk drug, provides a method for detecting impurities in benidipine hydrochloride with high detection capacity, and provides a method for detecting a beta isomer in the benidipine hydrochloride bulk drug. The technical problem that in an existing detection method, beta isomer impurities in the benidipine hydrochloride bulk drug are difficult to separate and detect is solved. According to the method for detecting the impurities in the benidipine hydrochloride bulk drug, liquid chromatography is adopted for detection, the detection limit is low, the sensitivity is high, and the accuracy is high. The method is widely applied to impurity detection in the benidipine hydrochloride bulk drug.

The invention provides a compound preparation containing an angiotensin II receptor antagonist and a calcium channel blocker. The compound preparation is prepared from benidipine hydrochlorine and olmesartan medoxomil. The compound preparation has the characteristics of stable and effective decomposition, less side effects, high safety, good tolerance and the like, and is suitable for strengthening long-term treatment compliance.

The present invention relates to benidipine hydrochloride (±)-(R*)-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinecarboxylate Nanoparticles of ester [(R*)-1-benzyl-3-piperidinol ester] hydrochloride and its ultrasonic preparation method.