40 results about "Heparin Derivative" patented technology

A therapeutic composition is provided including a polysaccharide or a cationic peptide dissolved in an organic substance. The polysaccharide can be heparin or a derivative of heparin. The cationic peptide can be L-arginine, oligo-L-arginine or poly-L-arginine. The organic substance can be formamide. A method of coating an implantable medical device is also provided, comprising applying the therapeutic composition to the device and allowing the organic substance to evaporate. The device can be a stent.

The invention provides methods and compositions relating to the detection and neutralization of heparin and heparin derivatives in vivo and in vitro. To neutralize heparin in a patient sample, a composition comprising a complex of a heparin-binding agent and a carrier compound is used prior to performing coagulation assays.

The present disclosure provides compounds, or pharmaceutically acceptable salts thereof, for inhibiting the growth of a microbe; treating a mammal having a microbial infection, malaria, mucositis, an ophthalmic infection, an otic infection, a cancer, or a Mycobacterium infection; killing or inhibiting the growth of a Plasmodium species; inhibiting the growth of a Mycobacterium species; modulating an immune response in a mammal; or antagonizing unfractionated heparin, low molecular weight heparin, or a heparin / low molecular weight heparin derivative.

The present invention provides compounds and methods for antagonizing the anticoagulant effect of an anticoagulant agent that is selected from UFH, LMWH, and a heparin / LMWH derivative in a patient comprising administering to the patient a compound of the invention or a salt thereof, or a composition comprising the same.

The invention discloses a kit for detecting antithrombase III (AT-III) in blood plasma by a developing substrate method. The kit comprises a heparin derivative, thrombin and a developing substrate reagent, wherein the heparin derivative is obtained by degrading heparin through heparinase II and cracking one or more unsaturated disaccharides from the heparin. The detection kit disclosed by the invention can avoid interference of a heparin cofactor II (HC-II) in a blood plasma sample, has the advantages of strong anti-interference capability, high flexibility, wide linear range, simplicity and rapidness in operation, strong instrument compatibility and the like, and has a wide application prospect.

The invention relates to a heparin derivative polysaccharide mixture and a preparation method and a medicinal composition thereof. Specifically, the heparin derivative polysaccharide mixture of the invention is a degradation product of heparin or heparin ester or heparin ester salt and is characterized in that the weight-average molecular weight is 3,100 to 4,500 Daltons, the activity of anti-coagulation factor Xa is high, and the activity of anti-coagulation factor IIa is low. The heparin derivative polysaccharide mixture of the invention has excellent antithrombotic performance, low side effect, and has no residues of adverse components such as organic base and dermatan sulfate and the like.

The invention discloses an anticancer medicament of heparin-taxol with low hemagglutinating resistance, which relates to a chemical bonding type anticancer medicament. The heparin-taxol medicament is prepared by heparin derivatives and taxol or taxol derivatives by the chemical bonding method, and the anticancer medicament not only has the blood-clot resistance lower than the heparin, but also has the anticancer property stronger than pure taxol medicaments.

The invention belongs to the field of biomedicine technique, and particularly relates to a preparation method of low-anticoagulant heparin with anti-tumor activity. The method comprises the steps of using heparin as a starting material to prepare completely desulfated heparin, carrying out N- site resulfation, carrying out enzymatic synthesis to obtain specific-site sulfated heparin through combination of Arylsulfotransferase-IV (AST-IV), 6-OST-1 and 2-OST by a 3'-phosphoadenosine-5'-phosphosulfate (PAPS) regeneration system based on the substances obtained in the previous steps, and carrying out N- site sulfation on the specific-site sulfated heparin to obtain the final low-anticoagulant activity heparin derivative with specific anti-tumor function.The heparin derivative avoids the side effects such as bleeding, decrease of blood platelet and osteoporosis when common heparin is used for the tumor patients, and is beneficial to expanding the clinical application ranges of the heparin drugs.

The invention provides a method for selectively modifying a heparin structure by using biological enzyme, which can improve anticoagulation activity of heparin, reduce combination of heparin with blood protein such as platelet factors and the like, and reduce toxic and side effects. The invention belongs to the field of biological medicine. The antithrombus and anticoagulation activities of the heparin derivatives prepared by the method are 2 to 3 times higher than common heparin medicament, the 2-O-sulfate and 6-O-sulfate contents are about 20 percent of the common heparin, and the combination capability of the heparin derivatives with the platelet factors is about 20 percent of the common heparin. The novel heparin derivatives have high anticoagulation activity and low side effect.

The invention discloses a heparin derivative-poloxamer temperature sensitive hydrogel and a preparation method thereof. The poloxamer is used as a framework material, and N-Acetylated low molecular weight heparin and prednisone are compounded to obtain the hydrogel. The mass ratio of the N-Acetylated low molecular weight heparin to the poloxamer is 15-90:100-300. The preparation method comprises the following steps that step 1, the N-Acetylated low molecular weight heparin is weighed and placed in a serum bottle, and a PBS buffer solution is added; step 2, a prednisone drug PBS buffer solutionwith mass concentration of 5% is added, stirring at the room temperature is conducted and lasts for 12-36 hours; and step3, the poloxamer is weighed, and the solution in the step 2 is added, solutionstirring is conducted at 4-10 DEG C and last for 12-36 hours. The heparin derivative-poloxamer temperature sensitive hydrogel has the excellent effect, is long in antibacterial time, and has simple procedures; and industrialization can be achieved easily, and popularization and application are facilitated.

The present invention provides compounds, or pharmaceutically acceptable salts thereof, for inhibiting the growth of a microbe; treating a mammal having a microbial infection, mucositis, an ophthalmic infection, an otic infection, a cancer, or a Mycobacterium infection; inhibiting the growth of a Mycobacterium species; modulating an immune response in a mammal; or antagonizing unfractionated heparin, low molecular weight heparin, or a heparin / low molecular weight heparin derivative.

Method for obtaining and expanding postembryonic hematopoietic stem cells from umbilical cord blood while avoiding unwanted differentiation. Initial cells from umbilical cord blood are proliferated and multiplied ex vivo in a stroma-free medium and in the presence of a regio-modified glycan or glycosaminoglycan. The regio-modified glycan or glycosaminoglycan, e.g. a heparin derivative, is N-desulfated, and N-reacetylated or N-reacylated, in essence, on C2 atoms. The heparin derivative advantageously comprises less than 5 percent of C3-O-sulfate, at least 60 percent C2-O-sulfate, and it is preferably added in a quantity of 15 to 50 mg / L to the medium in order to stop an unwanted differentiation. The stem cells generated in this manner can differentiate, after expansion, into myeloma cells and lymphatic cells, and they can be used as an immunotherapeutic agent against many diseases.

The invention relates to an anticoagulation-resistant heparin derivative. The anti-Xa factor of the anticoagulation-resistant heparin derivative is lower than or equals to 70IU / mg, preferably the anti-Xa factor is lower than or equals to 60IU / mg, preferably is lower than or equals to 50IU / mg, preferably is lower than or equals to 40IU / mg, preferably is lower than or equals to 30IU / mg, preferably is lower than or equals to 20IU / mg, preferably is lower than or equals to 10IU / mg, the anti-IIa factor is lower than or equals to 175IU / mg, preferably is lower than or equals to 170IU / mg, preferably islower than or equals to 160IU / mg, preferably is lower than or equals to 150IU / mg, preferably is lower than or equals to 140IU / mg, preferably is lower than or equals to 130IU / mg, preferably is lower than or equals to 120IU / mg, preferably is lower than or equals to 110IU / mg, preferably is lower than or equals to 100IU / mg, preferably is lower than or equals to 90IU / mg, preferably is lower than or equals to 80IU / mg, preferably is lower than or equals to 70IU / mg, preferably is lower than or equals to 60IU / mg, preferably is lower than or equals to 50IU / mg, preferably is lower than or equals to 40IU / mg, preferably is lower than or equals to 30IU / mg, preferably is lower than or equals to 20IU / mg, and preferably is lower than or equals to 10IU / mg.

The invention provides a method for single-step terminal sterilization process for bio-active heparin coatings on materials and biomaterials containing heparin used in medical devices, such as catheters, tissue engineering scaffolds, or drug delivery carrier materials. This may include any medical device or implantable that could benefit from improved antithrombotic and biocompatible heparin surfaces. Other relevant device examples may include heparin or a heparin derivative coated stents to reduce clotting and restenosis, dental or ophthalmological implants. These materials may comprise additional polymeric compositions such as polyethyleneimine, dextran sulfate or their modified forms. These polymers together with heparin coatings may be applied to other substrate of medical devices such as metal, ceramics or biologically derived materials.

Composition including a neutrophil elastase (NE)-targeting agent that counters the pathologic elements of respiratory inflammation is provided. NE-targeting agents primarily disrupt the association between NE and shed ectodomains of Syn-1, resulting in inhibition of the NE by protease inhibitors or anti-elastases. Non-anticoagulant heparin derivatives or fragments are exemplary NE-targeting agents. The composition preferably includes a carrier, such as chitosan or lactose in dry powder formulations, to facilitate delivery of the active agent. Use of the composition in manufacturing medicaments for treating respiratory diseases is also disclosed.

Polysaccharides, which are widely used as an anticoagulation drugs, especially heparin, are clinically administered only by intravenous or subcutaneous injection because of their strong hydrophilicity and high negative charge. Amphiphilic heparin derivatives were synthesized by conjugation to bile acids, sterols, and alkanoic acids, respectively. These heparin derivatives were slightly hydrophobic, exhibited good solubility in water, and have high anticoagulation activity. These slightly hydrophobic heparin derivatives are efficiently absorbed in the gastrointestinal tract and can be used in oral dosage forms. Methods of using these amphiphilic heparin derivatives and similarly modified macromolecules for oral administration are also disclosed.

The invention belongs to the field of prosthesis materials, and provides a keratoprosthesis optical center area. The keratoprosthesis optical center area is a surface-heparinized keratoprosthesis center material, and the surface-heparinized keratoprosthesis center material comprises a keratoprosthesis center material and a chemical modifier; the chemical modifier comprises a silane coupling agent and a heparin derivative or heparinoid derivative with anti-adhesion performance. According to the keratoprosthesis optical center area, the surface of polyvinyl alcohol hydrogel is chemically modified with the heparin derivative or the heparinoid derivative, and the excellent hydrophilia and high electronegativity of the heparin derivative or the heparinoid derivative are utilized, so that the keratoprosthesis center material with the surface provided with or containing the heparin derivative or the heparinoid derivative shows cell adhesive resistance. In addition, the keratoprosthesis optical center area is good in optical performance, water storage performance, swelling property and hydrophilic performance and high visible light transmittance.

The invention belongs to the technical field of biological medicines and in particular relates to a preparation method of a heparin-folic acid conjugate with low anticoagulant activity and tumor targeting property. The preparation method of the heparin-folic acid conjugate comprises the following steps: preparing a heparin derivative which is N-desulfated heparin by starting from heparin, connecting amidogen of the N-desulfated heparin and folic acid by virtue of an amido bond by using a cross-inking agent EDC in heterogeneous or homogeneous reaction, and removing unreacted and dissociated folic acid and EDC by dialyzing and freeze-drying a product to obtain a solid. The detection on the biological activity of the conjugate discovers that the conjugate has low anticoagulant activity and tumor targeting property.

The invention relates to a method for preparing a series of N-desulfated heparin derivative affinity chromatographic materials. The method comprises the following steps of: by respectively utilizing a de-2-O desulfated heparin derivative, a de-6-O desulfated heparin derivative and a de-N-desulfated and acetylated heparin derivative as ligands and using sepharose particles as a carrier, preparing a series of stable N-desulfated heparin derivative affinity chromatographic materials through the reductive amination reaction of the activated sepharose particles and all the heparin derivatives in the presence of a strong reducing agent. According to the method, heparin derivatives with different desulfated loci are used for preparing the affinity chromatographic materials, so that three heparin derivative affinity chromatographies with high stability and high activity are obtained; and the affinity chromatographic materials can be used for researching the structure and functions of heparin and separating and concentrating functional protein, tumor cells, virus and the like.

A mixture of oligosaccharides of heparin derivatives and its preparation and medicament. The mixture is characterised by a molecular weight lying between 3100 and 4500 Daltons, a high anti factor Xa activity, a low anti factor IIa activity and anti-thrombotic activity.

The invention discloses a kit for detecting antithrombase III (AT-III) in blood plasma by a developing substrate method. The kit comprises a heparin derivative, thrombin and a developing substrate reagent, wherein the heparin derivative is obtained by degrading heparin through heparinase II and cracking one or more unsaturated disaccharides from the heparin. The detection kit disclosed by the invention can avoid interference of a heparin cofactor II (HC-II) in a blood plasma sample, has the advantages of strong anti-interference capability, high flexibility, wide linear range, simplicity and rapidness in operation, strong instrument compatibility and the like, and has a wide application prospect.

The invention discloses a separation analysis method of derivatized heparin sulfate disaccharides containing free amino groups. The function relationship of the disaccharide quantity and mass spectrumdetection peak area can be used for quantitative determination of heparin and heparin sulfate disaccharide in practical biological samples. The separation analysis method can be used for detection ofheparin and heparin sulfate disaccharides, and especially heparin sulfate disaccharides containing free amino groups in liquid phase-mass spectrometry, and routine liquid chromatogram separating combined ultraviolet and fluorescent detector can be adopted in analysis. Important effect on clinical study on medical heparin, heparin sulfate, heparin derivatives, and disaccharides in various biological samples is achieved.

The invention discloses an artesunate heparin derivative as well as a pharmaceutical composition and an application thereof. The derivative is pharmaceutically acceptable salt having a high molecularcompound shown in a general formula (1) or a compound shown in the general formula (1): the formula (1) is shown in the description, in the formula (1), artesunate is bonded with heparin through esterbonds. In the artesunate heparin derivative, the content of the artesunate is 5 percent by mass to 50 percent by mass. The pharmaceutical composition of the artesunate heparin derivative comprises the artesunate heparin derivative or a mixture of the artesunate heparin derivative and a synergist. The derivative is characterized in that the artesunate is bonded with the heparin through the ester bonds, the pharmaceutical composition can be nano-particles which are self-assembled by the artesunate heparin derivative and have the particle size of 10 nanometers to 1000 nanometers, or nano-particles loaded with antimalarial medicines, and is used for preparing medicines for treating or preventing malaria caused by plasmodium.

The invention relates to an anticoagulant coating composition. The composition is prepared by compounding functional polyether long-chain quaternary ammonium salt macromolecules and heparin or heparin derivatives. The invention further provides a preparation method of the anticoagulant coating composition. The preparation method comprises the following process steps: A, preparing a polymer precursor; B, preparing a functional polyether long-chain quaternary ammonium salt high polymer material; and C, preparing the anticoagulant coating composition, including a, preparing a functional polyether long-chain quaternary ammonium salt polymer solution, b, preparing a heparin sodium solution, and c, preparing the functional polyether long-chain quaternary ammonium salt polymer-heparin composition. The invention further provides application of the anticoagulant coating composition. The composition is applied to a base material or various instruments made of the base material. Compared with the prior art, the composition has the advantages that the performance is firmer and more stable, the anticoagulant effect is greatly prolonged, and polyethylene glycol molecules on the upper side chain of the composition can achieve the effects of buffering and protecting in the contact process of the base material and a blood coagulation matrix, so that the base material also has a lasting anticoagulant effect.

The present invention relates to a process for the production of heparin derivatives having an average molecular weight of from about 4.6 to about 6.9 kDa and an anti-factor Xa activity of less than about 10 IU / mg, comprising the steps of oxidation of unfractionated heparin, depolymerisation and reduction of resulting terminal groups.

The invention discloses a method for separating and analyzing derivatized heparan sulfate disaccharides containing free amino groups. The functional relationship between the mass of the disaccharides and the peak area detected by mass spectrometry can be used for the quantification of heparin and heparan sulfate disaccharides in actual biological samples detection. The invention can detect heparin and heparan sulfate disaccharides in liquid phase-mass spectrometry analysis, especially the heparan sulfate disaccharides containing free amino groups, and can also be separated by conventional liquid chromatography and analyzed in combination with ultraviolet and fluorescence detectors. This has an important role in the study of clinical drugs heparin, heparan sulfate, heparin derivatives and disaccharide components of various biological samples.

A membrane artificial lung performs gas exchange between blood and a gas via the membrane by flowing the blood in one side of the membrane and flowing oxygen or an oxygen-containing gas in the other side of the membrane. The membrane has a hollow fiber membrane of poly-4-methylpentene-1 and an oxygen permeation rate Q(O2) at 25° C. of from 1×10−6 to 3×10−3 (cm3(STP) / cm2·sec·cmHg) and an ethanol flux of from 0.1 to 100 ml / min·m2. The membrane has, in the side of the blood flow, a surface having an ionic complex derived from: quaternary aliphatic alkylammonium salts; and heparin or a heparin derivative. The quaternary alkylammonium salts are a quaternary aliphatic alkylammonium salt having from 22 to 26 carbon atoms in total and a quaternary aliphatic alkylammonium salt having from 37 to 40 carbon atoms in total.

The present invention relates to the use of agents (including heparin derivatives) for the prevention and / or treatment of CNS damage.

The invention provides a method for single-step terminal sterilization process for bio-active heparin coatings on materials and biomaterials containing heparin used in medical devices, such as catheters, tissue engineering scaffolds, or drug delivery carrier materials. This may include any medical device or implantable that could benefit from improved antithrombotic and biocompatible heparin surfaces. Other relevant device examples may include heparin or a heparin derivative coated stents to reduce clotting and restenosis, dental or ophthalmological implants. These materials may comprise additional polymeric compositions such as polyethyleneimine, dextran sulfate or their modified forms. These polymers together with heparin coatings may be applied to other substrate of medical devices such as metal, ceramics or biologically derived materials.