59 results about "Milrinone" patented technology

A milrinone-sodium chloride injection for treating congestive heart failure is proportionally prepared from milrinone, sodium chloride and lactic acid.

The invention discloses a method for synthesising milrinone. The method comprises the following steps of: mixing 4-methylpyridine with acetylchloride in a solvent at a temperature below 10 DEG C; heating to react with or without a catalyst, and then adjusting the pH value of the reaction solution to 7-8 by sodium hydroxide aqueous solution; then directly adding saturated sodium hydrogen sulfite aqueous solution, and reacting; adjusting the pH value of the water layer obtained by the reaction by sodium hydroxide, and reacting to obtain a compound in formula (III); mixing the compound in formula (III) with glacial acetic acid, acetic anhydride and triethyl orthoformate, and then reacting at 50-100 DEG C to obtain a compound in formula (IV); cyclizing the compound in formula (IV) with alpha-cyanoacetamide in an alkaline condition to obtain a compound in formula (V). The process is more moderate in reaction conditions, simpler and more convenient to operate, and capable of greatly shortening the original reaction time, reducing cost and increasing yield simultaneously; the process is a preparation method for milrinone which is suitable for industrialized production.

The invention relates to a preparing method and a refining method for milrinone. The preparing method comprises the following steps: an absolute ethyl alcohol solution of 1-(4-pyridyl)-2-acetone is added dropwise into an absolute ethyl alcohol solution of ethoxymethylenemalononitrile, heat preservation is performed for 1-3 h under a condition of 20 DEG C-60 DEG C, then the temperature is increased to 75 DEG C-85 DEG C, a reaction liquid is cooled to 0-50 DEG C after a reaction is completed, solid-liquid separation is performed, and a solid is collected to obtain a product, wherein the mass ratio of ethoxymethylenemalononitrile to 1-(4-pyridyl)-2-acetone is (1.5-3):(1.5-2.5). According to the preparing method and the refining method, water is adopted to replace a purification solvent such as DMF (dimethyl formamide), methanol, ethanol and the like, so that not only are impurities removed effectively, all single impurities in a finished milrinone product is smaller than 0.1%, and solvent residues reach the standard, but also the production cost is reduced, product quality and yield are improved, and the methods are suitable for industrial production.

The invention discloses a new method for synthesizing milrinone. The method is characterized in that a compound of formula 3 and 4-pyridineboronic acid undergo a Suzuki coupling reaction to synthesize milrinone. The method has the advantages of easily available raw materials, high yield and simple post-treatment.

The present invention provides the application of high efficiency liquid phase chromatographic process in measuring the relevant matters and their content in milrinone. The flowing phase may consist of borax buffering liquid, methanol and water in the proportion of 1-5 to 20-50 to 50-80, preferably in the proportion of 1-3 to 20-40 to 60-70, and the borax buffering liquid has the preferable concentration of 0.05 M and pH value of 7.0.

Prophylactic strategies aimed at delivering vasodilators through inhalation in the pulmonary tree treat and prevent right ventricular dysfunction by reducing right ventricular afterload, facilitate separation from bypass and consequently decrease hemodynamic complications, morbidity and mortality. Examples of suitable vasodilatator include prostacyclin (flolan®), amrinone (inocor®), dobutamine (dobutrex®), nitroglycerine, nitroprussiate (nipruss®) and milrinone (primacor®).

The invention relates to a recrystallization purification method of milrinone, belonging to the field of active pharmaceutical ingredient refinement. The method comprises the following steps: adding a mixed solvent into a milrinone crude product, slowly heating, dissolving, adding activated carbon for decolorization, and carrying out vacuum filtration while the solution is hot to remove the activated carbon; cooling the filtrate to room temperature while slowly stirring, crystallizing, carrying out vacuum filtration, washing the filter cake with ethanol, and drying to obtain a white-like crystal; and adding the mixed solvent into the white-like crystal, slowly heating until all the white-like crystal is dissolved, cooling to room temperature while slowly stirring, and crystallizing to obtain a white crystal which is the purified milrinone with the content of up to 99.90%. The mixed solvent composed of water, ethanol and DMF (N,N-dimethylformamide) is utilized for filtration and purification, thereby comprehensively satisfying the requirements for solvent consumption, crystallinity and content. The product provided by the invention has obviously better appearance (such as crystallinity and color) than the product in the prior art.

The invention relates to a preparation method of high-purity milrinone as shown in a formula (I) described in the specification. The preparation method comprises the following steps: carrying out reflux reaction on N, N-methyl formamide dimethyl acetal (DMF-DMA) by taking 1-(4-pyridyl) acetone as a starting material, concentrating after the reaction is ended, adding normal hexane into residues to separate out solids to obtain an intermediate 1-(4-pyridyl)-2-(dimethylamino) vinyl methyl ketone; carrying out reflux reaction on the intermediate 1-(4-pyridyl)-2-(dimethylamino) vinyl methyl ketone and cyanoacetamide in the presence of sodium methylate, and regulating the pH value after the reaction is ended to obtain crude milrinone; and refining the crude milrinone by methanol / sodium methylate and alcohol / water to obtain a qualified milrinone product. The preparation method disclosed by the invention is simple in process operation, relatively small in pollution and suitable for industrial production.

A milrinone-sodium chloride injection for treating congestive heart failure is proportionally prepared from milrinone, sodium chloride and lactic acid.

The invention discloses a preparation method of high-purity milrinone. The method comprises the steps of dissolving 1-ethoxyl-2-(4-pyridyl) methyl vinyl ketone, cyanoacetamide and alkali into a monohydric alcohol-water system, reacting for 15-18 hours at -5 DEG C to 10 DEG C, adding water into reaction liquid and diluting to 1.5 times of the original volume after completing reaction, then adding activated carbon, stirring for 15-25 minutes at room temperature, filtering, regulating the pH value of filtrate to be 7 by using a hydrochloric acid solution, filtering, washing a filter cake by using water until the filtrate is colorless, refluxing and dissolving the filter cake by using 50vt% ethanol, filtering, and stirring and crystallizing the filtrate at -5 DEG C to 10 DEG C to obtain white solid milrinone with the purity of more than 99.9%. The method disclosed by the invention is simple and fast in process, high in yield and pure in product, and is more suitable for industrial production.

The present invention uses 1-(4-pyridyl)-acetone as a raw material for condensation reaction with triethyl orthoformate, and the condensate is directly cyclized with α-cyanoacetamide to obtain milrinone without purification, and is characterized in that The "one-pot" process is adopted, and the intermediate product is not purified. Milrinone is an important chemical product, which can be used as a cardiotonic drug, etc.

The invention discloses a preparation method for high-purity milrinone (shown as a formula (I), 1,6-dihydro-2-methyl-6-oxo-3,4-bipyridine-5-carbonitrile), and belongs to the field of chemical medicines. The method comprises: employing 4-methylpyridine as a raw material and acetylating with acetyl chloride, and hydrolyzing after the reaction is finished, so as to obtain a compound of a formula (III); mixing the compound of the formula (III) with glacial acetic acid, acetic anhydride and triethyl orthoformate, and reacting at 35 DEG C-45 DEG C, so as to obtain a compound of a formula (IV); performing cyclization on the compound of the formula (IV) and alpha-cyanoacetamide, so as to obtain a crude product of a compound of the formula (I); and refining the crude product of the formula (I) compound through an ethanol-water system, so as to obtain a high-purity refined product with the maximum interplanar spacing d of 8.39 + / - 0.02 Angstrom. The technology is relatively mild in reaction conditions and relatively simple in operation, and is capable of preparing the milrinone product with high purity and a single crystal form. The obtained milrinone crystal form is relatively excellent in solubility in normal saline or glucose, and is beneficial for improvement of the preparation quality.

The invention discloses a milrinone compound and a pharmaceutical composition containing the milrinone compound. According to the invention, lactic acid is adopted for helping solubilization and regulating the pH value, so that hyperchloremia which is possibly caused by extremely high Cl- concentration brought by pH regulation by adopting hydrochloric acid is avoided. In addition, the milrinone compound and the pharmaceutical composition are reasonable in prescription, high in quality standard, low in impurity content and high in bioavailability, has unique advantages in safety, effectiveness and quality stability, and also has an international level and more outstanding advantages.

The invention discloses injecta containing milrinone and a preparation method of the injecta. The injecta contains the components of 1g / L of milrinone, 0.5-2g / L of amiodarone hydrochloride, 0.8-1.0% (w / v) of sodium chloride and 4-10% (v / v) of ethanol. The dosage of a pharmaceutically acceptable acidic material is that pH of the injecta is 3.0-5.0, and the balance is injection water. According to the injecta disclosed by the invention, the symptoms of hemorrhagic shock can be effectively improved; generation of anaerobic respiration lactic acid is restrained under an anaerobic condition; the injecta has a good function on protecting liver and kidney, and the survival time of a sufferer is obviously prolonged.