70 results about "Heparinoid" patented technology

Preparation of synthetic monosaccharides, disaccharides, trisaccharides, tetrasaccharides and pentasaccharides for use in the preparation of synthetic heparinoids.

The invention relates to compounds which are polysufated oligosaccharide derivatives having activity as inhibitors of heparan sulfate-binding proteins and inhibitors of the enzyme heparanase; methods for the preparation of the compounds; compositions comprising the compounds, and use of the compounds and compositions thereof for the antiangiogenic, antimetastatic, anti-inflammatory, antimicrobial, anticoagulant and / or antithrombotic treatment, lowering of blood triglyceride levels and inhibition of cardiovascular disease of a mammalian subject.

The present invention provides preparations of monosaccharides, disaccharides, trisaccharides, and pentasaccharides of heparinoids. The present invention also provides novel monosaccharides, disaccharides, trisaccharides and pentasaccharides for use in the preparation of heparinoids.

The invention relates to a preparation and purification method of a carbohydrate library containing N-acetylated heparin. The method comprises the following steps: enriching oligosaccharide containing an N-acetylated structure through deep enzymolysis of low molecular weight heparin with heparinase I, then, preparing a series of heparin oligosaccharide crude samples ranging from disaccharide to tetradecasaccharide by Bio-Gel P10 gel chromatography, further separating the crude samples by means of strong anion high performance liquid chromatography and other methods, and respectively purifying the crude samples to obtain four hexasaccharide segments and three octasaccharide fragments; analyzing the disaccharide constituent of each purified oligosaccharide by compound enzymolysis with heparinase I, heparinase II and heparinase III and strong anion chromatography, and primarily deducing sequence structures of the four hexasaccharide and the three octasaccharide in combination with heparinase I substrate specificity; and finally, identifying the structure by electrospray ionization-ion trap-time of flight mass spectrometry (ESI-IT-TOF-MS). The preparation method provided by the invention can be used for solving the problem of difficulty in preparation and structure determination of oligosaccharide containing N-acetylated heparin, which makes research on a relationship between a special structure and functions of heparin / heparan sulfate developed further.

Plaster for topical use having an analgesic activity and at the same time being able to re-absorb haematomas, comprising: a substrate layer; an adhesive layer in the form of a hydrogel matrix containing a pharmaceutically acceptable diclofenac salt, heparin or a heparinoid; a protective film which can be removed at the moment of use.

The invention relates to compounds which are polysufated oligosaccharide derivatives having activity as inhibitors of heparan sulfate-binding proteins and inhibitors of the enzyme heparanase; methods for the preparation of the compounds; compositions comprising the compounds, and use of the compounds and compositions thereof for the antiangiogenic, antimetastatic, anti-inflammatory, antimicrobial, anticoagulant and / or antithrombotic treatment, lowering of blood triglyceride levels and inhibition of cardiovascular disease of a mammalian subject.

The present invention aims to provide an agent for promoting HGF production comprising, as an effective ingredient, a disaccharide comprised of an uronic acid residue (wherein an uronic acid means an iduronic acid or a glucuronic acid, and has the same meaning hereinafter) and a glucosamine residue that are connected by α1,4-glycosidic linkage or β1,4-glycosidic linkage, or an oligosaccharide of tri- to hexadeca-saccharides having a structure in which uronic acid residues and glucosamine residues are alternately and repeatedly connected by α1,4-glycosidic linkage or β1,4-glycosidic linkage, wherein at least one hydroxy group of the uronic acid residues and / or the glucosamine residues may be sulfated, alkylated, acylated or aminated, and / or the amino group at position 2 of at least one of the glucosamine residue(s) may be sulfated, alkylated or acylated, or a salt thereof. The agent of the present invention for promoting HGF production is useful to promote healing of damaged tissues or organs of a living body.

The invention discloses a preparation method of heparinoid. The preparation method comprises the following steps : adopting chondroitin sulfate as a raw material, and treating to obtain heparinoid after sulfonation reaction. In the sulfonation reaction, the adopted solvent is formamide and the adopted sulfonating agent is free sulfur trioxide, fuming sulfuric acid or pyridine sulfur trioxide. The preparation method of heparinoid, disclosed by the invention, has the advantages that the synthesis process is simple, the production and the operation are easily controlled, no special requirement exists for production equipment, the molecular weight range of a product is stable, the physicochemical indexes of the product are controlled in the quality standard range, and simultaneously the product is high in yield and the method is suitable for large-scale industrial production.

The present invention is related to heparin-like compounds characterized by their capacity of inhibiting collagen-induced platelet aggregation in flowing whole blood and their use for prophylactic treatment of arterial thrombosis associated with vascular or microvascular injury and interventions. Said properties are related to a high coupling density of negatively charged heparin or heparin-like glycosaminoglycan molecules, present in multiple heparin or heparin-like glycosaminoglycans as well as in proteoglycans containing said multiple heparin or heparin-like glycosaminoglycans or lower-molecular-weight heparin or heparin-like glycosaminoglycans connected directly or through spacer / linker molecules to globular core molecules. Heparin-like compounds, with said properties are obtainable from mammalian mast cells, by tissue extraction or cell cultivation. The heparin-like compounds of the present invention can also be produced by synthetical, semisynthetical and / or biotechnological methods and they are useful for manufacturing preparations, means and devices for local or topical application in prophylactic treatment of arterial thrombosis and its sequelae.

The invention relates to the technical field of material smashing, and discloses a blockage-free multilevel smasher for processing heparinoid. The blockage-free multilevel smasher comprises a feedinghopper, a multilevel smashing mechanism and a main discharging hole, wherein the multilevel smashing mechanism is in communication with the feeding hopper; the main discharging hole is in communication with the multilevel smashing mechanism; the multilevel smashing mechanism comprises a first-level smashing cavity and a second-level smashing cavity which is positioned below the first-level smashing cavity; a feeding hole A of the first-level smashing cavity is in communication with the feeding hopper; a discharging hole B of the first-level smashing cavity is in communication with a feeding hole C of the second-level smashing cavity; a discharging hole D of the second-level smashing cavity is in communication with the main discharging hole; and a shredder principle is adopted by the first-level smashing cavity. Compared with the prior art, the blockage-free multilevel smasher has the advantages that one smashing cavity is added, the shredder principle is adopted by the first-level smashing cavity, and two cutter shafts are used for driving a cutterhead to rotate towards each other to realize a blockage-free material smashing cavity. The two smashing cavities work simultaneously, large material blocks are smashed with the first-level smashing cavity into small material blocks, and the small material blocks enter the second-level smashing cavity for smashing and filtering througha screen, so that the feeding holes of the smashing cavities are prevented from being blocked, and the machine smashing efficiency is improved.

The present invention is related to heparin-like compounds characterized by their capacity of inhibiting collagen-induced platelet aggregation in flowing whole blood and their use for prophylactic treatment of arterial thrombosis associated with vascular or microvascular injury and interventions. Said properties are related to a high coupling density of negatively charged heparin or heparin-like glycosaminoglycan molecules, present in multiple heparin or heparin-like glycosaminoglycans as well as in proteoglycans containing said multiple heparin or heparin-like glycosaminoglycans or lower-molecular-weight heparin or heparin-like glycosaminoglycans connected directly or through spacer / linker molecules to globular core molecules. Heparin-like compounds, with said properties are obtainable from mammalian mast cells, by tissue extraction or cell cultivation. The heparin-like compounds of the present invention can also be produced by synthetical, semisynthetical and / or biotechnological methods and they are useful for manufacturing preparations, means and devices for local or topical application in prophylactic treatment of arterial thrombosis and its sequelae.

The invention discloses a preparation method of an extracorporeal circulation anticoagulant modified membrane. The preparation method comprises the following steps: 1, synthesizing carboxylated polysulfone / polyethersulfone; 2, synthesizing apixaban modified polysulfone / polyethersulfone; 3, preparing an apixaban modified polysulfone / polyethersulfone membrane. According to the extracorporeal circulation anticoagulant modified membrane and the preparation method thereof provided by the invention, an Xa factor inhibitor apixaban is grafted to base materials such as polyethersulfone (PES) and polysulfone (PSf), the base materials are modified by the apixaban, and membrane material wall-attached thrombus is efficiently inhibited through signal amplification, so that the membrane has strong anticoagulant and antithrombotic performance. The modification process is simple in synthesis condition, high in controllability and suitable for subsequent industrial large-scale production. According to the novel extracorporeal circulation anticoagulant modified membrane, the steric hindrance effect caused by heparin / heparinoid synthesis is effectively avoided, and meanwhile, the risk of severe bleeding caused by heparin-induced thrombocytopenia (HIT) is reduced.

The invention discloses a highly anti-coagulant polystyrene microsphere and preparation and application methods thereof. The highly anti-coagulant polystyrene microsphere comprises a polystyrene microsphere body and an anti-coagulant modification layer formed on the surface of the polystyrene microsphere body, wherein the anti-coagulant modification layer comprises a heparinoid functional layer, and the heparinoid function layer comprises an active heparinoid polymer prepared by polymerizing and crosslinking olefin acid monomers, sodium sulfonate monomers and crosslinking agent monomers. The preparation method of the highly anti-coagulant polystyrene microsphere comprises subjecting the olefin acid monomers, the sodium sulfonate monomers, the crosslinking agent monomers and initiators to polymerization and crosslinking reaction to obtain an active heparinoid aqueous solution, subjecting the polystyrene microsphere body to contact with the active heparinoid aqueous solution and then auto-polymerization and crosslinking under acid conditions to obtain the highly anti-coagulant polystyrene microsphere. The prepared highly anti-coagulant polystyrene microsphere is high in blood compatibility, and meanwhile, the preparation method of the highly anti-coagulant polystyrene microsphere is simple in technical process, easy to operate and implement and applicable to industrial productionand popularization.

An improved method for preparing a composition including a heparinoid, a local anesthetic, and a buffer for treatment of a lower urinary tract disease or condition can comprise either: (A) (i) providing a heparinoid in solid form or liquid form; (ii) providing a local anesthetic in solid form or liquid form; (iii) adding a liquid buffer to the heparinoid in solid form or liquid form; (iv) adding the local anesthetic to the mixture of the liquid buffer and the heparinoid; and (v) if necessary, adjusting the pH of the mixture of the liquid buffer, the local anesthetic, and the heparinoid so that a pH is achieved of from about 6.8 to about 8.3 is achieved without precipitation of the local anesthetic; or (B) (i)providing a heparinoid in solid form or liquid form; (ii) providing a local anesthetic in solid form or liquid form; (iii) mixing the heparinoid in solid form or liquid form and the local anesthetic in solid form or liquid form; (iv) adding a liquid buffer to the mixture of the heparinoid and the local anesthetic to form a mixture of liquid buffer, the heparinoid, and the local anesthetic; and (v) if necessary, adjusting the pH of the mixture of the liquid buffer, the local anesthetic, and the heparinoid so that a pH is achieved of from about 7.0 to about 7.8 is achieved without precipitation of the local anesthetic. The invention also encompasses a stable premixed liquid composition that avoids precipitation of the local anesthetic.

The invention relates to a local application emplastrum with analgesic activity and simultaneously capability of enabling hematoma reabsorption, which comprises a basal layer, a pharmaceutically acceptable diclofenac salt, a hydrogel matrix form adhesion layer with heparin or heparitin, and a protective membrane capable of being removed in use.

The invention discloses a gel containing a heparin-like composition, and belongs to the field of biotechnology. The gel containing the heparin-like composition is characterized by comprising 0.01-30 parts of mucopolysaccharide, 30-90 parts of a matrix material, 0.01-5 parts of a transdermal absorbent, 0.01-5 parts of an antioxidant, 0.01-5 parts of a bacteriostatic agent, 0.01-15 parts of a surfactant and 0.01-5 parts of a preservative. Under a synergistic action of a keratin softening agent and a natural moisturizing agent, the gel containing the heparin-like composition can inhibit the excessive growth of collagen fiber and reduce scar formation; the gel containing the heparin-like composition can retain moisture on the surface of skin to soften the collagen fiber and enhance the elasticity and has an effect of softening a hypertrophic scar.

The invention discloses an anti-restenosis 3D printing self-expansion degradable intravascular stent and a preparation method thereof. The modified heparinoid / selenocystamine / acryloyl chitosan, degradable hydrophilic layer 3D printing ink and degradable hydrophobic layer 3D printing ink are prepared, a hydrophilic layer and a hydrophobic layer of the intravascular stent are printed through a double-nozzle 3D printer, water-response self-driven expanding and expanding of narrow blood vessels are achieved through ultraviolet irradiation curing forming and chemical crosslinking bonding and bonding between the hydrophilic layer and the hydrophobic layer, driving deformation of the hydrophilic layer is achieved through printing grid design, and the 3D printing self-expanding degradable intravascular stent resistant to restenosis is formed through plane grid-shaped distortion expansion. The 3D printing self-expanding degradable intravascular stent prepared by the preparation method disclosed by the invention is short in deformation driving time, free of cytotoxicity and capable of efficiently and durably catalyzing endogenous RSNO to release NO, so that rapid endothelialization, smooth muscle cell migration and proliferation resistance and platelet adhesion and activation resistance are promoted, and the target of resisting vascular restenosis is achieved.

An object of the present invention is provide a method for sulfating a glycosaminoglycan in a solution of a non-organic solvent. In the present invention, sulfation reaction of a glycosaminoglycan is performed with a sulfating agent in a strongly basic solution of a non-organic solvent. In the present invention, pH of the strongly basic solution is preferably set to be 11.5 or higher. According to the present invention, for example, a glycosaminoglycan having heparin-like anticoagulant activity can be produced from N-acetylheparosan through one-pot procedure. In one embodiment, a sulfated glycosaminoglycan produced by the method of the present invention has a unique disaccharide composition and is expected to be a novel useful material.

The invention provides a low-molecular-weight heparin affinity purification medium, an affinity purification polyethylene imine dextran microsphere formed by the medium and a low-molecular-weight heparin affinity purification method, belonging to the field of biological medicine. The low-molecular-weight heparin affinity purification medium comprises three components: polyethylene imine, cross-linking substances and a microsphere structure, wherein the cross-linking substances comprise a cross-linking agent and a surfactant; the microsphere structure comprises microspheres and a microsphere carrier. The low-molecular-weight heparin can be well collected and other types of heparins are also removed when the low-molecular-weight heparin is purified by the purification medium; the purpose of well separating and purifying is achieved; the low-molecular-weight heparin can be used for quickly and efficiently preparing low-molecular-weight heparin sodium in a large scale.

The invention relates to a preparation and purification method of heparin hexasaccharides containing (i)N(i)-unsubstituted glucosamine (GlcNH3+). The preparation and purification method comprises the following steps: using enzymolysis low molecular weight heparin as the raw material, separating and purifying the heparin sodium hexasaccharide by methods of gel chromatography and ion exchange HPLC; preparing heparin pyridine hexasaccharide by using cation exchange resin and pyridine neutralization process; finally preparing heparin hexasaccharides with different numbers of GlcNH3+ by the (i)N( / i)-sulfate removal method, and separating and purifying the heparin hexasaccharide by the SAX-HPLC method. The preparation and purification method can specifically prepare the heparin oligosaccharides containing different numbers and sequences of GlcNH3+, and provide important oligosaccharides libraries for researching the structure and function of the GlcNH3+ residues in the heparin sulfate and the relationship between the GlcNH3+ residues and diseases.

The invention discloses a core-shell structured heparinoid microsphere based on graphene oxide grafted urease, and a preparation method and applications of the core-shell structured heparinoid microsphere. According to the preparation method, a graphene oxide two-dimensional nanosheet layer is taken as a base material, immobilizing urease on the surface of the base material by carbodiimide methodso as to obtain a core solution; in-situ cross-linking polymerization is adopted to prepare a heparinoid polymer solution to obtain a shell solution; and reverse-forward phase inversion method is adopted to obtain the core-shell structured heparinoid microsphere. The core-shell structured heparinoid microsphere is capable of removing urea with high efficiency in hemoperfusion, relieving patient pain, and can also be used for dialysate regeneration in hemodialysis, and provide technical support for a wearable artificial kidney.

The invention discloses a heparinoid composition-containing plaster and belongs to the technical field of biology. The heparinoid composition-containing plaster is characterized by comprising 0.01-80parts of mucopolysaccharide, 1-90 parts of a host material, 0.01-5 parts of a transdermal absorbent, 0.01-5 parts of an antioxidant, 0.01-5 parts of a preservative, 0.01-5 parts of a humectant, 0.1-20parts of a thickener, 0.01-5 parts of a bacteriostatic agent, 0.01-15 parts of a surfactant, and 0.01-5 parts of an emulsifier. Under the synergistic effects of a cutin softener and the natural humectant, the excessive growth of a collagenous fiber is inhibited, the formation of a scar is alleviated; the moisture on the surface of the skin is retained, the collagenous fiber is softened, the elasticity is strengthened, and the heparinoid composition-containing plaster has a softening effect on the hypertrophic scar.

The invention discloses a surface anticoagulation modification method of a hemodialyzer and an application of a hemodialyzer. The surface anticoagulation modification method includes the following steps: in a protective atmosphere, performing a reaction on a uniform mixing reaction system of a sodium sulfonate salt monomer containing an unsaturated double bond, an acrylic acid monomer, a long carbon chain olefin ester monomer, an initiator, and a first organic solvent at 50-100 DEG C for 8-24 h to obtain an amphiphilic anticoagulant copolymer; mixing the amphiphilic anticoagulation copolymer and a mixed solvent to form a modified solution, wherein the mixed solvent includes a second organic solvent, water and an interfacial melting agent; and allowing the membrane filament inner surface ofthe hemodialyzer to be in contact with the modified solution to obtain the hemodialyzer with high anticoagulant performance. The method can realize the rapid adsorption of heparin-like anticoagulantmolecules on the membrane filament surface of the hemodialyzer, a sufficient degree of adsorption force can be provided to ensure that the heparin-like molecules do not fall off in the dialysis process, and a good anticoagulant effect can be realized; and the method is simple in process, and convenient for industrial production and promotion.

The invention belongs to the technical field of biological fibers and functional materials and specifically relates to a low density lipoprotein adsorption microsphere and a preparation method and anadsorption material. The low density lipoprotein adsorption microsphere comprises a carrier; a hydrophobic functional group and heparinoid are coupled to the carrier; the mass ratio of the carrier, the heparinoid and the hydrophobic functional group is 1:(0.1-0.5):(0.1-0.5); the hydrophobic functional group consists of Delta-tocopherol and Alpha-tocopherol, wherein the content of the Delta-tocopherol does not exceed 5-8wt%. The low density lipoprotein adsorption microsphere provided by the invention has the advantages that the adsorption selectivity for LDL in whole blood is high, the adsorption rate of the LDL can reach up to 95% and above; more importantly, the damage to erythrocyte is low; the erythrocyte decrement rate is only 3.21%; and meanwhile, the filtering speed is high, the costis low, and the low density lipoprotein adsorption microsphere is suitable for large-scale promotion and application.

The invention discloses an application of macromolecular polysaccharide in removing inhalable particles in respiratory tracts. The invention further discloses an atomizing agent for removing the inhalable particles in the respiratory tracts. The atomizing agent comprises the following raw materials: macromolecular polysaccharide and water. The macromolecular polysaccharide is at least one of dextran, hydroxyethyl starch, cellulose, starch, glycogen, hemicellulose, alginic acid, glucosaminoglycan, heparan sulfate, succinylated gelatin, polygeline, chondroitin sulfate and hyaluronic acid. Respiratory tract spray of a macromolecular polysaccharide solution can increase respiratory tract wetness. Meanwhile, the macromolecular polysaccharide can effectively adsorb and wrap inhaled fine particulate matter (PM2.5). Finally, the macromolecular polysaccharide-fine particulate matter adsorption wrappage is pushed to the upper respiratory tract through ciliary movement of bronchial epithelium, and the macromolecular polysaccharide-fine particulate matter adsorption wrappage is discharged out of the body through cough.

The invention relates to a preparation and purification method for heparitin sulfate disaccharide, and a purified product thereof. The preparation and purification method comprises the following steps: eluting heparin disaccharide used as a raw material with a cation exchange resin, and regulating the pH value of the eluate to be weak acidic with pyridine to obtain heparin pyridine disaccharide; separately enabling the heparin pyridine disaccharide to react with a 1-methyl-2-pyrrolidone aqueous solution and an acetic anhydride, Na2CO3 and sulfur trioxide trimethylamine complex; and separating the reaction liquid with a gel resin, and purifying to obtain free amino disaccharide, N-acetyl disaccharide and N-sulfated disaccharide. The preparation and purification method is simple, solves the problems that a specific disaccharide structure can not be prepared in large scale, the preparation process comprises too many steps and the product price is expensive, and simultaneously further develops the study on the correlation between the special structure and function of heparitin sulfate.

The invention relates to heparinoid substance sulfonated citric acid modified chitosan and a preparation method thereof. The preparation method comprises the following steps: firstly, carrying out alkalization treatment on chitosan (CS) to obtain alkalized chitosan; adding an ethanol solution containing citric acid (CA) into the alkalized chitosan, and carrying out acylation reaction on the citricacid (CA) and the alkalized chitosan to obtain citric acid modified chitosan (CACS); then adding a sulfonation reagent prepared from chlorosulfonic acid and formamide into the citric acid modified chitosan to carry out sulfonation reaction, controlling the reaction temperature to be 60-70 DEG C, and refluxing for 3-6 hours; and after the reaction is finished, filtering, washing and carrying out normal-temperature vacuum drying to obtain the sulfonated citric acid modified chitosan (SCACS). According to the preparation method disclosed by the invention, citric acid modified chitosan is subjected to sulfonation treatment to prepare the sulfonated citric acid modified chitosan with a heparinoid structure, so that the hydrophilicity of chitosan is effectively improved, and the anticoagulationand protein pollution resistance of chitosan are improved.

The invention discloses antithrombotic heparin extracted from short necked clam and a preparation method and application of the antithrombotic heparin. The invention is characterized in that the structural formula of the heparin tetrasaccharide is as shown in (I), and the preparation method comprises the following steps: adding distilled water into short necked clam meat powder to dissolve a sample, regulating the pH value to 7.8-8.2, adding alkaline protease and papain to carryi out enzymolysis to obtain an enzymatic hydrolysate, carrying out enzyme deactivation, centrifuging, and taking a supernatant; transferring the supernatant into a balanced chromatographic column with macroporous ion exchange resin, taking distilled water as a solvent in the column, and combining and collecting elution components of a 1.5 M NaCl solution; concentrating the collected eluted component, adding ethanol, standing, centrifuging, taking a precipitate, alternately washing the precipitate with acetone and ethanol, dissolving the precipitate with water, centrifuging to remove insoluble substances, and repeating the operation for 3-4 times; and finally, dialyzing, and freeze-drying to obtain the antithrombotic heparin product extracted from short necked clam. The invention has the advantages of low bleeding side effect, mild anticoagulation effect and strong fibrinolysis effect.