34 results about "Nadroparin calcium" patented technology

The invention relates to a preparation and purification process for nadroparin calcium. The process comprises the following steps: depolymerization; reduction; recrystallization; chromatography; and filtration. According to the invention, the process can effectively extract a fragment with a narrow molecular weight distribution range; nadroparin calcium is obtained through improvement of a preparation process for low-molecular-weight heparin calcium, an out-dated solvent fractional precipitation method is changed, conditions for anion exchange chromatography are optimized, and the fragment both meeting requirements for molecular weight of LMWH in China and according with molecular weight distribution of nadroparin calcium are obtained through gradient?elution.

The invention discloses a method for producing nadroparin calcium 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 depolymerization, reduction, grading-alcoholic precipitation, calcium transfer, and freeze-drying treatment on the fine sodium heparin product, so that nadroparin calcium is obtained. The method disclosed by the invention has the advantages that the quality of nadroparin calcium 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 relates to a system and a method for detecting N-NO in nadroparin calcium by a chemical extraction-thermal energy analysis (TEA) method. The system comprises a TEA analyzer, a first-grade condensing device, a second-grade condensing device, a peristaltic pump, a heater, a reactor, an oxygen gas source, a vacuum pump and a nitrogen gas source. The method comprises the following steps: S1: preparing a solution; S2: carrying out instrument regulation preparation and the like; S3: opening two grades of condensing devices to enable the two grades of condensing devices to start condensing medium circulation; S4: adding one part of a reaction system from a sample inlet of the reactor and regulating a nitrogen gas flow speed and the like; S5: adding a standard product solution and a test sample solution and recording a chromatogram; calculating to obtain a result. The system provided by the invention is ingenious and simple and can be completely suitable for the detection of NO in the nadroparin calcium. The method provided by the invention has a more accurate result, lower detection limit and a more rapid detection speed and is simpler. By adopting the method provided by the invention, a procedure is greatly simplified; the method has extremely high sensitivity and high selectivity on a nitrogen-containing compound and is a detection method with extremely strong specificity.

The invention relates to the technical field of heparin medicines, in particular to high-purity nadroparin calcium. The high-purity nadroparin calcium is prepared by the steps of sodium removal, splitting, restoration-calcium-conversion, ultraviolet light irradiation, extraction-ultra-filtration, alcohol precipitation-pulping and centrifugation-drying; strong acid cation exchange resin is added into a heparin sodium solution to enable the heparin sodium solution to reach a certain pH range as well as to remove about 1 / 3 sodium ions from the heparin sodium solution through ion exchange and filtration so as to reduce the load of calcium-conversion in the late period; calcium oxide is used to replace the sodium hydroxide for neutralizing the reaction liquid to reduce the intake amount of the sodium ions in the reaction liquid; sodium borohydride and excessive calcium chloride are both added into the reaction liquid and are stirred for a proper duration for achieving a better calcium-conversion effect; the primary feed liquid is irradiated by the ultraviolet light, so that the vast majority of N-NO foreign matters are removed to enable the content of the N-NO to meet the most strict EP (European pharmacopoeia) demand.

The invention relates to a preparation process of nadroparin calcium, comprising the following steps: S1 degradation of heparin sodium; S2 reduction of degradation solution; S3 ultraviolet irradiation: using an ultraviolet lamp to irradiate the reduction solution to eliminate residual nitroso groups in the reduction solution compound, reducing the N-NO group content; S4 calcium transfer and concentration: use 5% calcium chloride solution to ultrafilter on the ultrafiltration membrane, and concentrate the reducing solution to a concentration of 1:10 in the solid-liquid ratio; S5 anion exchange layer Analysis: use anion exchange resin for chromatography, and collect the eluate; S6 freeze-drying to obtain the nadroparin calcium. The process uses anion exchange chromatography to control the molecular weight of low-molecular-weight heparin calcium, so that the molecular weight can be accurately controlled within 1%, and the yield can be increased to more than 50%, and the degree of automation is high, and the operation is convenient, which provides a powerful way to increase production capacity. Assure.

The invention discloses a production method of nadroparin calcium and belongs to the field of biomedicine. According to the method, crude heparin sodium is taken as raw material. Basing on enzymolysis and improved nitrite degradation method, nadroparin calcium high-quality product with particular average molecular weight (3800 to 5000Da) is prepared by enzymolysis, oxidative decolorization, ultrafiltration and impurity removal, ethanol precipitation and impurity removal, degradation, reduction, ultraviolet radiation, oxidation, Calcium replacement, nanofiltration, Ultrafiltration and refining, freeze-drying and other steps. The method provided by the invention has advantages of simple preparation technology, high bioavailability of the product, long half life in vivo, small hemorrhagic tendency and the like.

The invention discloses a production method for nadroparin calcium. Accoding to the production method, heparin sodium is adopted as raw material and subjected to degradation, deoxidation, ethanol precipitation, ion exchange resin calcium conversion, oxidation, filtration, precipitation and dehydration to obtain nadroparin calcium; the one-pot boiling technology is realized through oxidation, sterile filtration, precipitation and dehydration and the simplified operation is realized; compared with the disclosed methods, steps adopted in the heparin sodium preparation technology are fewer, the operation is simpler and more convenient, the calcium conversion is more complete and the yield is higher.

The invention discloses low-molecular-weight heparin derived from sheep, including sheep dateparin sodium, sheep nadroparin calcium, sheep tinzaparin sodium, sheep betaparin sodium and sheep bemiparin sodium. The low molecular weight heparins of sheep origin above all have common provenance characteristics. In terms of chemical structure, the content of the main disaccharide ΔUA2S‑GlcNS6S (ΔIS) is between 66%‑74%. Sheep low-molecular-weight heparin and pig-derived low-molecular-weight heparin have similar physical and chemical properties and biological activities, which expands the source of low-molecular-weight heparin drugs. The preparation method of sheep low-molecular-weight heparin introduced by the invention is simple and easy, and the process is stable. The obtained product is refined and can fully meet the requirements of various pharmacopoeias for the current low-molecular-weight heparin. Sheep low-molecular-weight heparin also has halal properties that porcine-derived low-molecular-weight heparin does not have. It has a huge market in the majority of Muslim populations, countries and regions, and can be used in anticoagulant, antithrombotic, anti-inflammatory, anticancer and halal drugs.

The invention discloses a production process of nadroparin calcium with low ethanol residue. The process comprises the following steps of: performing cracking, reduction, ultrafiltration and concentration on heparin sodium which is taken as a raw material to obtain a solution of the nadroparin calcium, and then regulating the concentration of the solution of the nadroparin calcium, the using quantity of anhydrous ethanol during an alcohol precipitation process, the using quantity of the anhydrous ethanol during a pulping process and the temperature during vacuum drying so as to finally obtain a finished product of the nadroparin calcium. According to the production process of the nadroparin calcium with the low ethanol residue, disclosed by the invention, the problem of the ethanol residue during the production process of the nadroparin calcium is solved, the ethanol residue in the nadroparin calcium is not more than 0.5% and in line with the requirements of European Pharmacopoeia EP7.0, the use of freeze-drying equipment is avoided, and the production process has the advantages of low price of the equipment, low operation energy consumption, convenience in maintenance, small floor area, easiness in production amplification, low production cost, stable process and the like.

The invention relates to a preparation and purification process for nadroparin calcium. The process comprises the following steps: depolymerization; reduction; recrystallization; chromatography; and filtration. According to the invention, the process can effectively extract a fragment with a narrow molecular weight distribution range; nadroparin calcium is obtained through improvement of a preparation process for low-molecular-weight heparin calcium, an out-dated solvent fractional precipitation method is changed, conditions for anion exchange chromatography are optimized, and the fragment both meeting requirements for molecular weight of LMWH in China and according with molecular weight distribution of nadroparin calcium are obtained through gradient?elution.

The invention relates to the field of medicine synthesis and discloses a preparation method of nadroparin calcium. The method of the invention firstly uses the sodium nitrite method to prepare the low-molecular-weight heparin sodium degradation liquid, and then obtains the reducing liquid through reduction. The reducing solution is filtered, the obtained filtrate is stirred evenly with calcium chloride solution and ultrafiltered, the ultrafiltrate is added with ethanol to precipitate, the precipitate is redissolved with water, filtered, the obtained filtrate is sterilized and freeze-dried to obtain the finished product of nadroparin calcium. The preparation process of the present invention provides a brand-new preparation idea, discards the hydrogen peroxide oxidation in the existing method and the calcium and sodium replacement of the cation exchange resin, integrates the ultrafiltration method and calcium chloride stirring to calcium, and cooperates with other optimizations steps, the ratio of anti-Xa / anti-IIa of nadroparin calcium is improved as a whole, the ratio of weight loss on drying of nadroparin calcium and the ratio of fractions with a molecular weight less than 2000 are improved, the process steps are greatly reduced, and the preparation efficiency is improved.

The invention discloses a method for producing nadroparin calcium from crude heparin sodium. The method uses crude heparin sodium as raw material, pretreatment by salt solution process, oxidation, ion exchange resin adsorption, washing, elution, and finally ultrafiltration and freeze-drying to obtain heparin sodium fine product, which is then depolymerized , reduction, graded alcohol precipitation, calcium transfer, and freeze-drying to obtain nadroparin calcium. The invention has the advantages of controlling the quality of nadroparin calcium from source and process, short production cycle, low production energy consumption and high product quality, and is suitable for large-scale industrial production.

The invention relates to the technical field of ultraviolet-visible spectrophotometric method detection and particularly relates to a method for rapidly detecting a nadroparin calcium product. The method comprises the step of detecting the concentration of nadroparin calcium in a solution through detecting the absorbance of a mixed solution in a range of 200nm-800nm by a spectrophotometric method, wherein the mixed solution contains fluorescein, the nadroparin calcium and a buffering solution; preferably, the mixed solution is formed by mixing an ethanol solution of the fluorescein, a nadroparin calcium solution, a sodium sulfate solution and the buffering solution. According to the method disclosed by the invention, an applied instrument is simple and the operation is simple and convenient; the concentration of the nadroparin calcium solution can be rapidly determined. The detection method provided by the invention is strong in anti-interference capability and strong in selectivity, and can be used for monitoring whether the contents of nitrite ions and calcium ions in the nadroparin calcium solution seriously exceed the standard or not. According to the detection method provided by the invention, a linear range is 3.0*10<-3>mol / L-4.5*10<-2>mol / L and a detection limit is 1.0*10<-3>mol / L; the detection method is completely applicable to the detection of a nadroparin calcium middle product and a nadroparin calcium final product and can be used for effectively monitoring a medicine production process of the nadroparin calcium.

The invention discloses solution concentration of nadroparin calcium determined by phenanthroline-zinc sulfate ultraviolet spectroscopy. Under the environment of buffered solution, Ultraviolet absorbance degrees of mixed solution which includes Zn2+ions, phenanthroline and the nadroparin calcium are determined, and then the concentration of the nadroparin calcium is determined by quantity. According to the solution concentration of the nadroparin calcium determined by the phenanthroline-zinc sulfate ultraviolet spectroscopy, a phenanthroline-zinc sulfate ultraviolet spectroscopy test system is applied, quick quantitative determination of the solution concentration of the nadroparin calcium can be achieved. The linear range of an analytical method of the solution concentration of the nadroparin calcium determined by the phenanthroline-zinc sulfate ultraviolet spectroscopy is 1.184%-16.33%, meanwhile, the analytical method of the solution concentration of the nadroparin calcium determined by the phenanthroline-zinc sulfate ultraviolet spectroscopy has good anti-jamming capability and can be applied in the practical production process of nadroparin calcium medicines and capable of carrying out concentration determination to intermediate product solution or finished product solution.

The invention discloses a method for producing nadroparin calcium from crude heparin sodium. The present invention uses crude heparin sodium as a raw material, after adding water to dissolve, and then precipitates and removes impurities in the crude heparin sodium by centrifugation and secondary salting out, then degrades and reduces with nitrous acid to obtain low-molecular-weight heparin containing free sulfate radicals, and then adds chlorinated Barium removes free sulfate radicals produced by degradation, then uses anion exchange resin, and adjusts appropriate parameters for calcium conversion and final impurity removal, and finally oxidative decolorization, filter sterilization, dehydration and drying to obtain nadroparin calcium raw material. The invention uses crude heparin sodium as a raw material, reduces the production cost, improves the yield of nadroparin calcium by simplifying the process steps, reduces the potency loss of the nadroparin calcium, can ensure the safety of the product, and is convenient for large-scale industrial production.