96 results about "Enoxaparin sodium" patented technology

The invention relates to a preparation method for directly producing enoxaparin sodium from crude product heparin sodium. The preparation method comprises the following steps of: taking the crude product heparin sodium as a raw material, performing fractionated precipitation through an organic solvent to remove most of impurities in the crude product heparin sodium, and then removing part of residual impurity proteins, pigments and other impurities by oxidation through hydrogen peroxide so as to get the high-purity heparin sodium which is in line with the production requirements of the enoxaparin sodium; and taking the high-purity heparin sodium as an intermediate product, preparing a heparin quaternary ammonium salt, preparing heparin benzyl ester, performing alkaline depolymerization on the heparin benzyl ester, neutralizing with an acid, performing alcohol precipitation, refining, decoloring, dehydrating and drying to get an enoxaparin sodium finished product. By adopting the method disclosed by the invention, the use of the organic solvent is greatly reduced, the production efficiency is improved, the influences on the environment are reduced, the enoxaparin sodium finished product which achieves or is better than European Pharmacopoeia 7.0 version is obtained, and the method is simple to operate and can realize industrialized production.

The invention relates to a purifying manufacture method for Yino sodium heparin that adopts long chain quaternary ammonium salt salinization heparin, after taking benzyl chloride esterification, gaining the raw Yino heparin raw product. After taking decoloration by active carbon and macropore adsorptive resin, the sodium heparin product could be gained. The invention is easy to realize industrializing producing.

The invention discloses a technology for preparing enoxaparin sodium by membrane separation. The technology is characterized in that the enoxaparin sodium is sequentially subjected to treatments such as quaternary ammonium salt salinization, benzyl esterification and alkalinity degradation so as to realize beta-degradation, oxidation decoloration and filtration edulcoration, and filter liquor is subjected to ultrafiltration treatment to obtain an enoxaparin sodium product which can meet average molecular weight and molecular weight distribution range. According to the technology disclosed by the invention, membranes with different hole diameters are used for realizing ultrafiltration so as to control molecular weight and molecular weight distribution of a control product, and the enoxaparin sodium product with high purity and high activity is prepared; hydrogen peroxide oxidation decoloration and activated carbon filtration edulcoration are adopted, the impurities in a reaction system are effectively removed, and the product chromaticity is remarkably improved; the weight-average molecular weight of the prepared enoxaparin sodium is 3800-5000, the size and distribution range of molecular weight are ideal, the measured anti-FXa resistant / anti-FII a specific value is greater than 3.3, the main factor anti-FII a activity for causing a bleeding danger is greatly reduced, the anti-FXa activity for playing an embolism resisting action is relatively improved, and the validity and security advantages of the product are obvious.

The invention discloses enoxaparin sodium. The average molecular weight of the enoxaparin sodium is between 3500-5500 dalton, thrombolytic biological activity is 100-125IU/mg, and the ratio value of resistance to Xa and IIa resistance is between 3.3-5.3. A production purification method of the enoxaparin sodium comprises preparation of heparin benzyl chloride ammonium salt, preparation of heparin benzyl ester, purification of heparin benzyl ester, preparation of enoxaparin sodium and purification of enoxaparin sodium. By means of the enoxaparin sodium, the molecular weight and distribution range of a product are controlled, and the quality of a fine enoxaparin sodium product meets the quality standard of the european pharmacopoeia. The enoxaparin sodium adopts a crude product of heparin sodium as an initial raw material and can effectively reduce production cost. The refined heparin benzyl ester stabilizes the final quality of the product. Purification difficulties are simplified, the coloring problem in the production is effectively solved, and the product quality is improved.

The invention relates to a preparation method for low-molecular heparin originated from a new species. The preparation method comprises the following steps: (1) fully dissolving heparin sodium prepared from raw materials bovine lungs, ox intestines and/or goat intestines in water, and adding a benzethonium chloride solution to prepare heparin benzethonium chloride salt; (2) dissolving the heparin benzethonium chloride salt in dichloromethane, adding benzyl chloride, stirring the mixture to react, reducing the temperature and adding a sodium acetate methanol solution to prepare heparin benzyl ester; (3) dissolving the heparin benzyl ester in water, adding sodium hydroxide, reducing the temperature after reaction, adjusting the pH to neutral, adding sodium chloride, and then adding alcohol to prepare an enoxaparin sodium crude product; and (4) dissolving the enoxaparin sodium coarse product in water, and purifying and drying the mixture to obtain enoxaparin sodium. According to the preparation method provided by the invention, the condition that the low-molecular heparin can be obtained by heparin sodium prepared from bovine lungs, ox intestines and goat intestines is found for the first time, and the prepared low-molecular heparin is lower in molecular weight compared with that of existing low-molecular heparin, so that the biological activity is higher and the low-molecular heparin has a wide market application prospect.

The invention discloses a method for producing enoxaparin sodium by using crude sodium heparin products. The method is implemented by taking crude sodium heparin products as a raw material through the steps of pretreating the crude sodium heparin products by using a salt hydrolysis process; sequentially carrying out oxidation, ion exchange resin adsorption, washing and elution on the obtained object; sequentially carrying out ultrafiltration and freeze-drying on the obtained product so as to obtain a fine sodium heparin product; and sequentially carrying out salifying, esterification, depolymerization, oxidation, alcoholic precipitation, and freeze-drying treatment on the fine sodium heparin product, so that enoxaparin sodium is obtained. The method disclosed by the invention has the advantages that the quality of enoxaparin sodium is controlled from the aspects of source and process, the production cycle is short, the energy consumption of production is low, and the quality of products is high, therefore, the method is suitable for large-scale industrial production.

The invention discloses islamic enoxaparin sodium. The average molecular weight of the islamic enoxaparin sodium is 3,500 to 5,500 Daltons, thrombolytic bioactivity is 100 to 125IU/mg, and the ratio of Xa resistance to IIa resistance is 3.3 to 5.3. A method for producing and purifying the islamic enoxaparin sodium comprises the following steps of: purifying a crude heparin sodium product, salinizing heparin sodium, drying, esterifying, performing alcohol precipitation, performing alkali degradation, performing alcohol precipitation, oxidizing, performing alcohol precipitation, performing fine filtering, and drying to obtain a finished product. The crude bovine lung heparin sodium product is taken as an initial raw material, so that production cost can be effectively produced; the heparin sodium is purified by trypsin, so that the method is convenient to operate, yield is high, and the prepared fine heparin sodium product has the advantages of stable quality, high purity, high titer and the like; and by refining heparin benzyl ester, the quality of a final product is stabilized, purification difficulty is reduced, the problem that a pigment is generated during production is effectively solved, and the quality of the product is improved.

The present invention is enoxaparin and its preparation process, and features that the preparation process includes the following steps: dissolving sodium heparin in water, dissolving benzethonium chloride in water, mixing these two kinds of solution to react, vacuum suction filtering, washing the solid with water and stoving to obtain quaternary ammonium salt of heparin; dissolving the salt in dichloromethane, adding benzyl chloride to react, adding methanol solution of sodium acetate to produce precipitate, suction filtering, washing the solid with methanol and stoving to obtain heparin benzyl ester; dissolving heparin benzyl ester in 0.1N water solution of sodium hydroxide, adding sodium chloride, membrane filtering after dissolving, adding methanol to separate out precipitate, suction filtering, washing and stoving solid to obtain coarse enoxaparin sodium product; and purifying to obtain refined enoxaparin sodium product. The present invention has low production cost and high product quality.

The invention belongs to the pharmaceutic preparation field, and in particular relates to an enoxaparin sodium injection and a preparation process thereof. The processes of adding antioxygen of the assigned type and regulating the pH are applied to the preparation of the enoxaparin sodium injection. The injection is specifically prepared from enoxaparin sodium, vitamin C, L-cysteine and water for injection, the pH regulating agent is used for regulating the pH of the injection at 5.5-7.5. Compared with the prior art, the technical scheme provided by the invention is capable of greatly improving the stability of the enoxaparin sodium injection, the aspects that the color of the medicine liquor is darkened, the activity is reduced, and the pH of the medicine liquor is greatly reduced are obviously improved; and the process is simple and suitable for the large-scale industrial production.

The invention relates to a production method for enoxaparin sodium. Started from an original material (macromolecule heparin sodium), the technical processing under a specific condition is performed and a suitable solvent is selected, an end product of enoxaparin sodium meeting European pharmacopoeia standard can be acquired, the environmental pollution is less, the yield is high and the molecular weight and titer of the finally acquired end product can be efficiently and perfectly controlled.

The invention discloses a production method of enoxaparin sodium, which comprises the following steps: carrying out enzymolysis on heparin sodium, carrying out HPLC (high performance liquid chromatography) analysis, calculating the contents of various peaks by a peak area normalization process, determining the varieties of disaccharides and tetrasaccharides of the heparin sodium subjected to enzymolysis according to a standard spectrum of disaccharides and tetrasaccharides after heparin sodium enzymolysis, comparing with the contents of disaccharides and tetrasaccharides of the standard spectrum, and selecting the satisfactory heparin sodium raw material to produce the enoxaparin sodium. The method is simple and effective, can ensure the safety and effectiveness of the product, controls the quality of the enoxaparin sodium from the source, can avoid the waste of the active pharmaceutical ingredient heparin sodium, greatly saves the cost and enhances the production efficiency.

The invention provides an enoxaparin injection preparation. The enoxaparin injection preparation is prepared from, by weight, 20 parts of enoxaparin sodium and 1-2 parts of stent agent. The invention further provides an industrial production method of the enoxaparin sodium injection preparation. The enoxaparin injection preparation is good in stability and clinical safety, simple in preparation technology, appropriate in cost and suitable for mass industrial production.

The invention relates to a synthetic method of affinity precipitation medium and application thereof to preparation of enoxaparin sodium. The preparation method is as below: salinizing heparin with benzethonium chloride salt in a heparin sodium solution purified by the affinity precipitation medium; esterifying the heparin benzethonium chloride to generate heparin benzyl ester; carrying out depolymerization on heparin benzyl ester in alkaline conditions; the precipitating by ethanol to obtain an enoxaparin sodium crude product; and oxidizing for decolorization by hydrogen peroxide to obtain the enoxaparin sodium fine product. The invention uses crude heparin sodium as a raw material and employs the affinity precipitation medium for purification, so as to effectively remove impurities bonded or non-boned with the heparin, ensure integrity of the natural structure of heparin, increase the activity yield of heparin and provide the basis for the stability and controllability of the subsequent preparation process of the enoxaparin sodium. The invention reduces the production cost, improves production efficiency, and is more suitable for industrial production.

The invention discloses a method for preparing and purifying enoxaparin sodium. After a crude enoxaparin sodium product is subjected to centrifugal separation and alcohol precipitation impurity removal, the finished enoxaparin sodium product meeting pharmacopeia standards can be obtained. The method is high in yield and easy and convenient to implement, and the product is good in clarity and capable of meeting requirements of the pharmaceutical industry.

The invention provides a heparanase composition capable of complete specific enzymolysis of enoxaparin sodium. The heparanase composition is a mixture of heparanase II and heparanase III, wherein the enzyme activity ratio of heparanase II to heparanase III is 3: 1. According to the invention, the heparanase composition can realize the complete specific enzymolysis of enoxaparin sodium and is reduced to obtain 1, 6-anhydride derivatives, and the contents are in an acceptable range; the heparanase composition is free from heparanase I to reduce the introduction of enzyme impurities, so that the method is more reliable, is an important supplement for several pharmacopoeia methods, has high practical use value and significance.

The invention belongs to the field of medicine, and relates to an RP-IP-HPLC (reverse-phase ion-pair high-performance liquid chromatography) method for collecting enoxaparin oligosaccharide. The method comprises the following steps: (a) a tetrose component mixture is collected from enoxaparin, wherein an enoxaparin sodium solution with the concentration of 50-70mg/ml is separated with high-resolution gel permeation chromatography, and the tetrose component mixture is obtained; (b) single tetrose components are collected from the tetrose component mixture with RP-IP-HPLC, wherein the tetrose component mixture is taken and made into a water solution with the concentration of 10mg/ml and is pre-separated with the reverse-phase ion-pair high-performance liquid chromatography, the pre-separated tetrose components are made into water solutions of 1mg/ml respectively and then are separated and purified with the reverse-phase ion-pair high-performance liquid chromatography; (c) the collected single tetrose components are made into the water solutions of 1mg/ml and are subjected to structural analysis through ESI-MS (electrospray ionization mass spectrometry).

The invention discloses a preparation method for improving the clarity of enoxaparin sodium. The method comprises the following steps: dissolving a crude product of enoxaparin sodium by adopting sodium chloride with concentration of more than 3.5%(w/v), ionizing quaternary ammonium salt bonded with the crude product of enoxaparin sodium through replacement reaction, and precipitating out enoxaparin sodium by using high-quantity ethanol or methanol. Compared with the prior art, the preparation method provided by the invention is easy and feasible, the product yield is high, and the clarity is relatively good.

The invention belongs to the technical field of medicine and relates to a refining method of enoxaparin sodium. The refining method solves the problems of the prior art, utilizes an enoxaparin sodium crude product as a raw material, realizes combination of hydrogen peroxide oxidation decoloring and methanol grading alcohol precipitation, and adopts a two-step decoloring and methanol grading alcohol precipitation method. The decolored agent obtained by the refining method is basically colorless, colored impurities can be effectively removed and an enoxaparin sodium finished product is obtained by spray drying. The refining method realizes synthesis of the enoxaparin sodium finished product satisfying the requirement EP 7.0. The refining method has product collection easiness and is suitable for industrial expanded production. Through integral cooperation of decoloring, grading alcohol precipitation and spray drying, product clarity is less than or equal to that of a turbidimetric liquid 0.5, European pharmacopoeia EP 7.0 requirements are satisfied, production processes are simple, product collection is easy and the refining method is provided for industrial production.