54 results about "Citicoline sodium" patented technology

The present invention is process of preparing citicoline sodium. The preparation process includes the biotransformation of material including 5'-cytidylate, phosphorylcholine, potassium hydroxide and glucose with yeast as the biocatalyst; extraction and separation with active carbon as the adsorbing carrier, Cl- type ion exchange resin as the separating carrier and re-compounded water-alcohol mixture as the analyzing reagent; and product purification with alcohol solvent as the crystallizing solvent. Compared with available technology, the present invention has the advantages of high product yield and high product purity.

The invention discloses a salting-out and solvating-out crystallization method for citicoline. The method comprises the following steps: adding inorganic sodium salt which accounts for 1 to 20 percent of citicoline and a solvating agent which is 1.0 to 4.0 times the volume of a staring citicoline aqueous solution to a citicoline aqueous solution with a pH value between 5.0 and 8.0 and a concentration between 10 and 400 g/L; stirring the materials at a rotating speed controlled between 20 and 230 rpm at a temperature of between 10 and 40 DEG C; performing pumping filtration after complete crystallization; washing the obtained product with ethanol; drying the obtained product in vacuum; and obtaining the citicoline sodium salt crystals with the purity higher than 99 percent. The method has the advantages that the method obviously improves the quality of final products, raises crystallization yield stability, can control the particle size of the crystals by changing crystallization temperature or the states of a flow field, and is simple to operate, good in repeatability and suitable for the industrial production of the citicoline.

The present invention relates to a production process of citicoline. It is characterized by that said production process includes the following steps: firstly, adding water and glucose into a reaction tank, then adding yeast, making fermentation, after fermentation adding inorganic salt and choline phosphate, the adding cytidine monophosphate solution, an adding cane sugar, heating, then quickly-cooling by using water, pressing reaction liquid, washing by using water, removing salt from obtained clear liquor; then pressing said clear liquor and making said clear liquor be fed into a carbon column, rinsing said carbon column by using pure water, then using ethyl alcohol solution to make elution, collecting citicoline sodium; then vaporizing and concentrating eluent, diluting concentrate and making it be fed into a macroporous ion exchange resin column, then washing said column by using water and making elution, concentrating eluent, heating the collected citicoline sodium solution, removing impurity by utilizing ultrafiltration device, decolouring, adding ethyl alcohol and stirring them, storing the above-mentioned material in a refrigeration house and staying overnight; then making crystal solution undergo the processes of centrifugal separation, vacuum drying, bagging, weighing, sealing and dry-storage.

The present invention provides a citicoline sodium compound and new method thereof, wherein purification is performed via active carbon adsorption, acidification reaction and preparing chromatographic column, finally a citicoline sodium compound with high purity is obtained; the shortage of low raw material purity in the prior production is recovered, simultaneously the quality of preparation product is improved, and side effects are reduced. Compared with the prior art, the method has the advantages of simple and easy technology, low cost, high yield and high product purity; the method is suitable for industrial production; and the citicoline sodium prepared by the refining method of the present invention is suitable for being used in preparation of neural activation agent pharmaceuticals.

The invention relates to citicoline sodium glucose injection, belonging to the field of pharmaceutical preparations. The citicoline sodium glucose injection provided by the invention is composed of 3 g of citicoline sodium, 40 g of glucose, 1.8 g of glycine, and 1.3 g of citric acid; the pH value is adjusted to 5.5-5.6 by using sodium hydroxide; and water for injection is added till the citicoline sodium glucose injection is 1000 ml.

The invention provides citicoline sodium tablets and a preparation method for directly compressing powder of citicoline sodium into tablets. The citicoline sodium tablets provided by the invention are prepared from citicoline sodium, cellactose 80, sodium carboxymethyl starch, magnesium stearate and micro-powder silica gel. The tablets provided by the invention are prepared by adopting a powder direct tablet compression method and the problem that citicoline sodium granulated by a traditional wet process is easy to hydrolyze is solved; meanwhile, the conditions that the tablet weight different is relatively great and the dissolution uniformly is relatively poor, which are easily caused by direct powder compression, are solved through screening prescriptions and setting technological parameters; the quality stability and the safety of products are greatly improved.

The invention discloses a citieoline sodium injection with good quality and low cost, and provides a method for preparing the injection simultaneously. The citieoline sodium injection provided by the invention is prepared from 1,000-5,000g of citieoline sodium, 5g of versene disodium and 20,000ml of water for injection, and is 2-5ml per tube. The preparation method comprises the following steps of: weighing each component; heating the water for injection to 28-30 DEG C, adding 0.02-0.05 percent of injection active carbon, adsorbing for 20-30 minutes, and filtering; and heating a feed liquid to 60-65 DEG C, preserving heat for 8-10 minutes, adding 0.02 percent of injection active carbon, stirring, dissolving, decarburizing, filtering, lowering temperature of the feed liquid to be below 40 DEG C, and performing split charging. Due to the adoption of the method, the pollution levels and endotoxin levels of relevant substances of a product and microorganisms are effectively controlled, and the stability and light inspection yield of the product are increased.

The invention relates to a method for detecting related substances in a pharmaceutical preparation containing citicoline sodium. High performance liquid chromatography is adopted to analyze a system applicability solution, and the separation degree and theoretical plate number of citicoline sodium peak among the citicoline sodium peak and adjacent impurities and each known impurity in a chromatogram are recorded; the separation degree among citicoline sodium and adjacent impurities and each known impurity is greater than 1.5, when the theoretical plate number of the citicoline peak is greaterthan 2000, then a test solution and a contrast solution are analyzed and detected, the chromatogram is recorded for three times of the retention time of a main component peak, and the impurity number,type, relative percentage content, peak area and separation degree between the peaks are read and calculated from the recorded chromatogram; and the peak area in the chromatogram is calculated to obtain the content of each impurity. Compared with the prior art, the method for detecting the related substances in the pharmaceutical preparation containing citicoline sodium is simple and convenient,quick and good in durability, the impurities in the citicoline sodium can be effectively detected, and the method for detecting the related substances in the pharmaceutical preparation containing citicoline sodium is good in applicability, and high in accuracy and precision.

The invention discloses a method for separating and purifying citicoline sodium from microbial fermentation liquor. The method comprises the following steps: (1) heating and flocculating citicoline sodium fermentation liquor, performing solid-liquid separation to obtain a clear liquid, and performing ultrafiltration and nanofiltration continuous pretreatment on the clear liquid to obtain a pretreating liquid; (2) pretreating the pretreating liquid on a strong-base anion exchange resin pre-column, adsorbing effluent through a strong-base anion exchange resin spin column, eluting with a sodium chloride solution, mixing high-purity eluting liquids, and performing vacuum concentration and alcohol-precipitation crystallization to obtain a citicoline sodium crude product; and (3) decolorizing the citicoline sodium crude product with activated carbon, performing filtration, concentration, alcohol-precipitation crystallization and vacuum drying to obtain a citicoline sodium finished product which has good quality, high yield, low cost and small pollution.

The invention discloses a 11/2 water citicoline sodium compound and a preparation method of the 11/2 water citicoline sodium compound, wherein each molar of citicoline sodium contains 11/2 molar of water. The citicoline sodium compound is prepared by dissolving a crude product of citicoline sodium into purified water, stirring, dissolving; adding an activated carbon, decarburizing; regulating thepH by using an acid, stirring evenly; slowly adding ethyl alcohol dropwise, adding a seed crystal after finishing adding dropwise, controlling the temperature, leaving to stand, crystalizing, filtering, washing a filtered material with ethyl alcohol, and drying in vacuum. The 11/2 water citicoline sodium compound is low in hygroscopicity and impurity content and good in stability, and has a broader application prospect. Meanwhile, the invention further discloses a pharmaceutical composition preparation of the 11/2 water citicoline sodium compound. The pharmaceutical composition preparation ofthe 11/2 water citicoline sodium compound is better in stability compared with the previous preparation.

The invention discloses a synthetic method of citicoline sodium. The synthetic method comprises the following steps: adding 5'-cytidylic acid, calcium phosphorylcholine chloride, ATP, an aqueous magnesium chloride solution and a Tris-HCl buffer solution into a reaction vessel, and carrying out uniform mixing; then, adjusting a pH value to 6.0-8.0, adding CMP phosphokinase, nucleoside diphosphate kinase and choline phosphate-cytidyltransferase, and carrying out a stirring reaction for 4-10 hours at a temperature of 25-50 DEG C; and conducting high-speed centrifugation, and taking a supernatantto obtain citicoline sodium. Compared with the traditional citicoline sodium synthesis process, the synthetic method provided by the invention is environment-friendly in a synthesis route, stable in yield and is beneficial for reducing energy consumption and protecting the environment, so the synthetic method is suitable for large-scale industrial production.

The invention discloses a citicoline sodium medicine composition and pharmaceutical application of the citicoline sodium medicine composition to preventing and treating ovarian cancer. The citicoline sodium medicine composition contains citicoline sodium and a natural product compound (I) which is separated from dried roots of radix polygalae and is of a novel structure. Only common effects of preventing and treating the ovarian cancer can be realized when the citicoline sodium and the natural product compound (I) are individually used, but effects of preventing and treating the ovarian cancer can be obviously improved when the citicoline sodium and the natural product compound (I) are used with each other, and accordingly the citicoline sodium medicine composition can be developed to obtain medicines for preventing and treating the ovarian cancer. Compared with the prior art, the citicoline sodium medicine composition and the pharmaceutical application have the advantages of outstanding substantial characteristics and obvious advancement.

The invention relates to a 1/2 water citicoline sodium compound and a preparation method of the 1/2 water citicoline sodium compound, wherein each molar of citicoline sodium contains 1/2 molar of water. Specifically, the preparation method is as follows: adding a crude product of citicoline sodium, sodium calcium edetate and sodium sulfite into a mixed solution of purified water and acetone, stirring and dissolving; adding activated carbon, stirring, adsorbing, filtering; using an acid to regulate the pH of a filtrate, stirring evenly; slowing adding isopropanol dropwise into the above solution, standing, crystalizing, filtering, washing a filtered material, and drying to obtain the 1/2 water citicoline sodium compound. The 1/2 water citicoline sodium compound is good in flowability, low in impurity content and hygroscopicity, fast in dissolution and good in stability, and has a broader application prospect.