201 results about "Sodium heparin" patented technology

The invention discloses a heparin sodium and its preparing process for extracting sodium heparin from pig small intestine mucous membrane through the steps of, enzymolyzing 2709 proteinases to obtain the liquemine solution, charging sodium chloride, elevating temperature to condensate the animal protein in the pig small intestine mucous membrane, thus resulting ionic exchange for the obtained heparin sodium, performing elution with the strong alkalinity ion exchange resin after washing diluted sodium chloride solution and high concentration sodium chloride solution, subjecting the eluted heparin sodium in alcohol solution for settlement and drying to obtain the liquaemin sodium crude product, acidifying the soluble heparin crude product to remove acidic proteins, then performing purification operation of double oxidization.

The invention discloses a preparation method for separating biochemical medicaments from mucous membranes of porcine small intestines, in particular a preparation method for producing heparin sodium by using porcine small intestines. The preparation method for producing the heparin sodium by using the porcine small intestines is characterized by comprising the following steps of: preparing intestinal mucosa, and performing enzymolysis, adsorption, elution, precipitation, desalination, dehydration and drying to obtain the heparin sodium. The method has the advantages that: the heparin sodium has high yield, low activity loss and stable quality; the waste liquor is pollution-free in discharge and can be recycled; the problem of stench in a heparin sodium workshop is solved by adopting a workshop waste gas purification treatment device; and 2,000 to 2,400 pieces of porcine small intestines are needed for producing 0.1 billion units of heparin sodium by using the conventional process, only 1,400 to 1,600 pieces of porcine small intestines are needed for producing 0.1 billion units of heparin sodium by using the preparation method, and the effect and the activity of the heparin sodium are greatly improved, so that the production cost is greatly reduced, and the profit can be improved by over 40 percent.

The invention relates to a recombinant human basic fibroblast growth factor gelling agent and the process for preparation, which comprises recombinant human basic fibroblast growth factor (rh-bFGF) stock solution 0.1-100% (W/W), medicinal auxiliary material 0-99.9% (W/W), the stock solution comprises effective treatment dose of recombinant human basic fibroblast growth factor (rh-bFGF) 0.01-1% (ug/g), NaCl 0.01-20% (W/W), phosphates cushioning liquid 2m Mol - 200m Mol, and right amount of water for injection, the medicinal auxiliary materials can be selected from: carbomer 940NF, sodium hyaluronate, trehalose, mannitol, dextran 40 and sodium heparin.

A biologic material for preventing adhesion after operation is prepared from chitosan and sodium hyaluronate through preparing their solutions, proportionally mixing, defoaming, loading in mould, freeze drying to become film or tube, immersing the mixed liquid, flushing by distilled water drying and sterilizing. It is possible to attach the antiadhering medicine to it. Its advantages are high attachment, mechanical strength and antibacterial power, and better biocompatibility and bioactivity.

The invention relates to a method for extracting sodium heparin, which comprises the following steps: (1) enzymic hydrolyzing intestinal mucosa in a conventional method, and adopting enzyme preparation for the hydrolysis: mixture which is formed by mixing prolease, papain and lipase at a mass ratio of 1 to 4: 1 to 3: 0.1 to 0.3, and selecting the prolease from one of 2709 enzyme, AS1.398 enzyme and pancreatin; (2) resin adsorbing in a conventional method; (3) resin eluenting in a conventional method; (4) settling out the sodium heparin in a conventional method; (5) purifying the sodium heparin in a conventional method; (6) drying the sodium heparin in a conventional method to obtain the pure sodium heparin. An improved solution is characterized in that precipitator is added before filtering and hydrolyzing the mixture in the step 1. The method has simple process, short production period, simple and convenient operation and less investment, and is applicable to the industrialized mass production. The purity of the heparin can reach 100 to 120IU/mg, the extraction efficiency can reach 100 million IU/1700 to 1800 chatterlings, the extraction efficiency can be improved by 20 to 30 percent, consumed salt can be reduced by 30 to 50 percent, water can be reduced by 50 to 70 percent, energy can be reduced by 30 to 40 percent, and the recycling rate of the crude protein can reach 60 percent.

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 growth factor-loading silk fibroin/collagen bracket material and a preparation method thereof. The material is prepared from the raw materials of collagens, growth factors, silk fibroin, polylysine (PLL) and heparin sodium. A loose layer fibroin/collagen film and a compact layer fibroin/collagen film form a double-layered structure, and growth factor-loading PLL-heparin sodium nanoparticles are compounded in the middle of the double-layered structure. The preparation method comprises the following steps: preparing the loose layer fibroin/collagen film and the compact layer fibroin/ collagen film; preparing the growth factor-loading nanoparticles, compounding the fibroin/ collagen film and the nanoparticles and the like. The growth factor-loading silk fibroin/collagen bracket material disclosed by the invention plays a directional differential slow release role on the loaded growth factors and can fully maintain the activity of the growth factors and effectively prolong the action time of the growth factors, so that the material is a good guided tissue regeneration material for prosthodontic treatment of impaired and damaged tissues.

The invention relates to a method to separate and purify dermatan sulfate and low molecule heparan sulfate from sodium heparin by-product. It uses the by-product of producing sodium heparin as raw material taking fractional precipitation through alcohol to gain raw dermatan sulfate; uses nitrite and nitrous acid ester compounding as oxidant to degrade the heparan sulfate into low molecule heparan sulfate and taking fractional precipitation through alcohol to separate high purity dermatan sulfate and low molecule heparin sulfate.

The present invention discloses a method for quickly precipitating and separating oversulfated chondroitin sulfate in sodium heparin. The method adopts an ion exchange method to remove a mass of impurities combined with a hydrogen peroxide oxidation method, which greatly improves the color and the potency of the sodium heparin, quickly precipitates and separates the oversulfated chondroitin sulfate in the sodium heparin by alcohol, which ensures the yield coefficient of the sodium heparin more than 85 percent and the potency more than 180u/mg, and each index totally satisfies the USP and EP standards. The present invention is more remarkable than the reported acetone extraction method; because the solvability of the oversulfated chondroitin sulfate and sodium heparin is very low to ethanol and acetone and the like, the separating effect of the organic solvent extraction method is bad, specifically, the separating effect is more unconspicuous when the oversulfated chondroitin sulfate in sodium heparin is higher. The quick precipitation method is designed according to the feature that the absolute molecular weight of the oversulfated chondroitin is greater than the sodium heparin and the differences of structure and the like. The method is featured with simple operation and notable separating effect.

The invention discloses a reagent, a method and a kit for measuring small-and-dense lipoprotein. The reagent comprises first agents and second agents, the first agents include 1-500 mg/L reagent A, 10-300 U/mL sodium heparin, 0.1-90 mmol/L divalent metal ion, 0.5-2 KU/L cholesterol esterase, 1-3.5 KU/L cholesterol oxidase, 100-300 KU/L catalase, 0.1-10 mmol/L 4-amino antipyrine, 0.05-6% KU/L surfactant A, and the second reagents include 0.2-10 KU/L peroxidase, 0.3-20 mmol/L Trinder's chromogen compound, 0.01-0.3% sodium azide and 0.05-12% surfactant B. The reagent can be used for specifically detecting sdLDL. By using the method, sdLDL can be detected specifically. The kit is simple and convenient to operate.

The invention discloses a process for producing low molecular sodium heparin by using raw sodium heparin as a raw material, which comprises the steps of: producing a sodium heparin solution; degradingthe solution; neutralizing the solution; collecting a precipitation; producing low molecular raw sodium heparin; producing low molecular fine sodium heparin and the like. The low molecular sodium heparin has the characteristics of rich sources of the raw material, high yield, stable and reliable quality, high purity, low cost, long curative effect, no toxic or side effect, simple process, convenient operation and no 'three wastes' discharge, has the effects of coagulation resistance, thrombosis resistance, tumor resistance, inflammation resistance, allergy resistance and the like and the efficiency of regulating blood lipid, has significant curative effect and wide application range, can be produced into injections, capsules, ointments and the like, is convenient for massive production, and is widely used for producing coagulation resistant low molecular sodium heparin.

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 provides a novel process for producing sodium heparin, which comprises the following steps of enzymolysis, gum exchange adsorption, resin washing, heparin eluting, alcohol precipitation,precipitation once more, dehydration drying, crushing, mixing and packaging. The process has mature flow, convenient operation, no emission of waste intestinal dregs and overproof wastewater, complete enzymolysis reaction, short reaction time of 30 hours, low production energy consumption, low reaction temperature of between 70 and 80 DEG C, heparin extracting ratio over 90 percent, high unit yield of the heparin, only need of 1,700 pieces of small intestines of pigs for each 100 million units of heparin, low production cost, increase of economic benefit over 30 percent per 100 million units,no emission of dirty intestinal dregs and overproof wastewater, and suitability for large-scale production.

The invention discloses a separation purification method of refined heparin sodium. The method comprises the steps of: (1) salt hydrolysis; (2) adsorption and elution; (3) ethanol precipitation; (4) first oxidation; (5) secondary oxidation; and (6) precipitation. The method provided by the invention purifies crude heparin sodium by a two-step oxidation, not only reduces the production cost, and has no need for special equipment, also the prepared refined heparin sodium product has good purity and high recovery rate, and the quality and activity of heparin sodium are ensured.

The invention relates to a method for extracting heparin sodium, and particularly relates to a method for extracting heparin sodium from a small intestine of a pig and co-producing protein powder. The method comprises steps of (1) carrying out enzymolysis and salt hydration; (2) separating protein powder out; and (3) extracting heparin sodium: adsorbing, eluting, precipitating and drying. The method improves the yield of heparin sodium, furthermore, the equipment for co-production has higher usage rate than single producing equipment, saves resources, and can lower the production cost of heparin sodium and protein powder. The small intestine of the pig is fully used and is improved in additional value, furthermore, the pollution of waste liquid and waste residue containing protein to environment is reduced, and the waste liquid and waste residue are turned into wealth.

The invention provides a method for separating and cultivating rat hepatocytes. A rat is anaesthetized by Nembutal and is given sodium heparin for anticoagulation; portal catheterization is carried out; two-step reperfusion is carried out for perfusion; a digestive mature liver is taken off; hepatocytes are collected in Hanks liquid containing 1 percent of bovine serum albumin (BSA); hepatocyte suspension is screened by a screen stencil; after the filtrate is centrifugated and deposited, the deposit is collected in Leibovitz's-15(l-15) complete medium; the density of hepatocyte is adjusted to 3 to 6 *10<5>/ml and inoculated on a culture plate coated with rat tail collagen in the environment of temperature of 37 DEG C and 5 percent of CO2; and unattached and dead hepatocytes are removed by changing medium after 4 hours of inoculation, and the hepatocytes can be used for experiment after 20 hours of cultivation. The method is easy, simple and stable, has low cost and high efficiency, can obtain high-activity hepatocytes, is easy to attach, and can be used for pharmacological and toxicity experiments and popularized in common laboratories.

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 a synthesis method of a 6-O-carboxymethyl chitosan sulfation product. The method comprises the following steps: (1) chitin alkaline treatment of chitin; (2) carboxymethylation of C6-O site of chitin; (3) deacetylation reaction of 6-O-carboxymethyl chitin; and (4) sulfation of 6-O-carboxymethyl chitosan. The synthesis method disclosed by the invention is a bran-new method for selectively replacing and controlling the replacement rate by using chitin. The synthesis product of the method provides N-site -SO3H with main anticoagulant activity and introduces -COOH, so that a lot of -COOH and SO3H which have negative electricity in the molecular structure are regularly distributed, and an anticoagulant effect of heparinoid is generated by the synergistic effect. High molecular polysaccharide is a heparinoid drug which is selectively modified by chitin via a safe reagent, so that reagent pollution of bulk drugs is reduced, the virus contamination risk of heparin biological extraction is avoided, the safety performance of the drug in the clinical experiment is more excellent in theory as compared with heparin sodium, so the 6-O-carboxymethyl chitosan sulfation product provided by the invention is expected to serve as a cheap direct thrombin inhibitor to replace heparin sodium anti coagulation drugs.

The invention refers to a heparin compound and its preparation method and application. The heparin compound is a heparin zinc-potassium double salt demonstrated by the formula of R(ZnOH)aKb. The R represents the heparin radical and a is between 3 and 5, b between 1 and 3. The heparin compound can be made through the following preparation method: dissolve the sodium heparin into the water and contact with the cinnamene cation exchange resin to get the heparin solution; add an amount of zinc hydroxide and potassium hydroxide to the heparin solution, whisk and dry it and get the mentioned solid heparin compound. The heparin compound can be used as the anticoagulant agent as well as the main material of the anti thrombus medicine. The heparin zinc-potassium as the anticoagulant agent meets not only the requirements of not affecting the components' balance and stability of the blood samples to be tested but also the requirement of the solubility in the blood. When it is chosen as the main resource of the anti thrombus medicine, the heparin zinc-potassium releases slowly, has long effect of medicine and no toxicity and is good for the zinc-adding of the human body.

The invention discloses a method for extracting a sodium heparin crude product. The method comprise the following steps:: adding alkali to fresh intestinal mucosa water, keeping temperature and discharging material, and filtering by using a nylon mesh cloth of 90-120 meshes; carrying out a secondary extraction on filter residues and combining filtering liquids in the two steps of filtering; heating the combined filtering liquids and adding fresh porcine pancreas to react for 1 to 2 hours; putting resins into the filtering liquids to elute; adding alcohol for static deposition in the filtered elution liquid; extracting the deposit and placing in a Busher funnel to vaccumize; and dewatering and drying to obtain the heparin crude product. Combining an enzymolysis method with a salt method, the invention has the advantages of low concentration of the waste liquid and easy post-treatment. Because the process adopts the two-step decomposition of the salt method and the enzymolysis method, the sodium heparin dissociates completely with higher yield.

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 provides a coating method for an activated carbon adsorbent for blood perfusion. Firstly, coating film is formed on the surface of activated carbon with chitosan, then crosslinking is executed with epichlorohydrin to increase the strength of the film, and finally heparin sodium having an anticoagulant effect is grafted to the surface of the film. The crosslinked chitosan film can improve the blood compatibility of the activated carbon and decrease particle falling of the activated carbon; the heparin sodium having an excellent anticoagulant property is grafted on the film so thatthe blood coagulation phenomenon occurring when blood is in contact with the surface of the activated carbon can be decreased, and the safety of a perfusion device is improved.

The invention belongs to the technical field of medicines and relates to a compound low-molecular heparin sodium liposome gel and a preparation method and application thereof. The compound low-molecular heparin sodium liposome gel comprises low-molecular heparin sodium, asiaticoside, lipid components, a membrane softening agent and gel matrix components, wherein the low-molecular heparin sodium and asiaticoside are pharmacological active ingredients, and based on the total gel of 100g, the content of the low-molecular heparin sodium is 5000-35000IU, and the content of the asiaticoside is 0.1-2.5g. The preparation method comprises the following steps of: (1) preparing a compound low-molecular heparin sodium liposome by employing an ethanol injection-ultrasonic method or ethanol injection-high pressure homogenizer method; (2) preparing a blank gel; (3) adding the compound low-molecular heparin sodium liposome into the blank gel, uniformly stirring, and obtaining the compound low-molecular heparin sodium liposome gel. The gel is mainly used for treating skin injury and scar.