20 results about "Clopidogrel" patented technology

The invention relates to the technical field of medicines, in particular to application of benzbromarone in preparation of antithrombotic drugs. The research finds that benzbromarone clinically used for treating hyperuricemia can be combined with HSP47 on platelets to inhibit the interaction between the HSP47 and collagen so as to reduce platelet activation and thrombosis, which prompts that benzbromarone is an HSP47 inhibitor with an anti-platelet effect; benzbromarone has the effects of inhibiting mouse common carotid artery thrombosis and relieving cerebral ischemia reperfusion injury. Experiments finally confirm that benzbromarone can inhibit formation of common carotid artery thrombosis, does not affect the blood coagulation function, is low in cytotoxicity, has the drug effect similar to that of aspirin and clopidogrel which are commonly used at present, and can become an effective and safe therapeutic drug for cerebral arterial thrombosis.

The disclosure discloses a method for treating a plasma sample containing (7aS,2′S)-2-oxo-clopidogrel and a method for determining the same, which belongs to the technical field of pharmaceutical analysis and solves the problem in the prior art that there is not yet a method for determining the concentration of (7aS,2′S)-2-oxo-clopidogrel in plasma. The method for treating a plasma sample containing (7aS,2′S)-2-oxo-clopidogrel comprises: taking whole blood containing (7aS,2′S)-2-oxo-clopidogrel, adding a reducing agent solution and collecting plasma. The method for determining (7aS,2′S)-2-oxo-clopidogrel in plasma according to the disclosure uses the treatment method as described above to treat a sample to be determined, and includes the following steps: S1. Whole blood treatment: taking whole blood, adding a reducing agent solution, centrifuging, and collecting plasma; S2. Plasma sample pre-treatment: adding a protein precipitant and an internal standard working solution to the plasma, vortexing and then centrifuging, and taking the supernatant; S3. LC / MS / MS determination. The method of the disclosure is simple, easy to operate, and has good stability, specificity and sensitivity, and accurate determination results.

The utility model discloses a novel clopidogrel mother liquor recovery device which comprises a neutralization tank, an outlet of the neutralization tank is connected with a raw material preheater through a guide pipe, an outlet of the raw material preheater is connected with a rectifying tower through a guide pipe, and a top outlet of the rectifying tower is connected with a fractional condenser through a guide pipe; after being neutralized, raw materials are pumped into the raw material preheater through the raw material pump to be preheated, the preheated raw materials enter the rectifying tower to be rectified, distillates at the top in the rectifying tower are segregated through the segregation device, distillates at the top enter the superheater through the tower top distillates outlet, and the distillates are filtered by the membrane assembly, and then are separated by the membrane assembly. The filtered waste liquid enters a condenser to be condensed, and the material to be recycled enters a raw material preheater, then enters a finished product cooler to be cooled, then enters a dehydrated product storage tank and is pumped out by a finished product pump; the mother liquor permeated by the condenser enters the neutralization tank again; and recovery of mother liquor and harmless treatment of waste liquor are realized.

The invention discloses a method for producing a clopidogrel intermediate through biological catalysis chiral resolution, which comprises the following steps: screening an esterase mutant capable of efficiently resolving the clopidogrel intermediate (R, S)-2-(2-chlorphenyl)-2-(2-thiophene ethylamino) methyl acetate through molecular modification to obtain (S)-2-(2-chlorphenyl)-2-(2-thiophene ethylamino) methyl acetate; according to the present invention, the biocatalysis activity and the stereoselectivity are high, the reaction efficiency is improved, the position of the biocatalysis step in the whole synthesis route is beneficial to the improvement of the efficiency of other chemical steps, the overall conversion rate, the enantiomer excess value and the product purity, and the production cost can be significantly reduced. In addition, the method also has the common advantages of enzymatic synthesis, such as simplicity and convenience in implementation and operation, greenness and environmental protection, easiness in product separation and the like.

The invention belongs to the field of drug synthesis, and relates to a method for simultaneously separating clopidogrel and camphorsulfonic acid, which comprises the following steps: reacting (+ / -)-clopidogrel with (+ / -)-10-camphorsulfonic acid in an organic solvent to generate a crystal precipitate of (R)-10-camphorsulfonate of (S)-clopidogrel, filtering, and separating out the crystal precipitate of (R)-10-camphorsulfonate of (R)-clopidogrel. Or separating out the crystal precipitate of the (S)-10-camphorsulfonate of the (R)-clopidogrel, filtering, and then separating out the crystal precipitate of the (R)-10-camphorsulfonate of the (S)-clopidogrel. And four chiral substances, namely (S)-clopidogrel, (R)-clopidogrel, (R)-10-camphorsulfonic acid and (S)-10-camphorsulfonic acid, can be co-produced at the same time.

The invention relates to the technical field of drug analysis and detection, in particular to a method for detecting specific impurities in a compound preparation clopidogrel aspirin tablet. The method comprises the following steps: mixing a compound preparation clopidogrel aspirin powder with an extraction solvent, carrying out ultrasonic extraction, filtering, and taking supernate to prepare a test solution; a test solution is detected by adopting a high performance liquid chromatography, and chromatographic conditions are as follows: a chromatographic column is an octadecyl bonded silica gel chromatographic column; a mobile phase A is an ion pair buffer salt solution; and the mobile phase B is acetonitrile. According to the method disclosed by the invention, effective separation of seven specific clopidogrel impurities and six specific aspirin impurities can be realized, and the responsivity is relatively good.

The invention provides a medicine for simultaneously reducing the risks of bleeding and microvascular occlusion. Specifically, the invention provides a composition, the composition comprises (a) a first active component with a therapeutically effective amount, and the first active component is clopidogrel or a pharmaceutically acceptable salt thereof; (b) a therapeutically effective amount of a second active ingredient, wherein the second active ingredient is salvianolic acid B or a pharmaceutically acceptable salt thereof; and (c) a therapeutically effective amount of a third active ingredient, wherein the third active ingredient is ginsenoside Rg1 or a pharmaceutically acceptable salt thereof. The first active component, the second active component and the third active component can generate a bidirectional synergistic protection effect, can effectively reduce microvascular occlusion, can effectively prevent bleeding, reduces the dosage of a single drug, and reduces the toxicity of the drug.

The invention discloses a method for preparing clopidogrel by using sulfur hexafluoride, which comprises the following steps: taking methanol and (S)-(2-chlorphenyl)-6, 7-dihydrothiophene [3, 2-C] pyridine-5 (4H)-acetic acid as raw materials, taking an alkaline substance as an additive, and reacting in a solvent in the presence of sulfur hexafluoride, a photocatalyst and illumination to obtain the clopidogrel. According to the method disclosed by the invention, SF6 is activated under a photocatalytic condition, and an esterification reaction of carboxylic acid is realized by utilizing an SF6 decomposition product to prepare clopidogrel; wherein the decomposition product of SF6 is used as a condensation reagent, the greenhouse gas SF6 is effectively activated by the method, carboxylic acid esterification is realized by fully utilizing the decomposition product of SF6, clopidogrel is prepared, and the SF6 is turned into wealth from waste; the raw materials required by the method are simple and easy to obtain, the reaction conditions are simple and convenient, and the method is green and energy-saving and has higher application value.

The invention discloses a clopidogrel aspirin tablet and a preparation method thereof, the clopidogrel aspirin tablet is prepared by tabletting an aspirin layer and a clopidogrel layer, the aspirin layer is composed of an aspirin tablet core, two isolation layers and an enteric-coated layer inserted between the two isolation layers, and the dosage of talcum powder is reduced to be less than 40% of the total weight of an enteric-coated material. According to the clopidogrel aspirin tablet and the preparation method thereof, on the premise that the coating process is smooth and free of precipitation and flocculation phenomena, the prepared clopidogrel aspirin tablet has good pressure resistance and acid resistance and good long-term dissolution stability by controlling the selection of a specific plasticizer (preferably polyethylene glycol 400) in the aspirin layer and optimizing the dosage, and the clopidogrel aspirin tablet is equivalent to an original reference preparation.

The present application provides a pharmaceutical preparation containing aspirin, a preparation method thereof, and an application thereof, wherein the pharmaceutical preparation contains aspirin enteric-coated microspheres and a second active ingredient, clopidogrel, wherein the aspirin enteric-coated microspheres are composed of a matrix and aspirin dispersed in the matrix; the matrix is ​​composed of hypromellose phthalate and ethylcellulose; and aspirin accounts for 50-70% of the weight of the enteric-coated microspheres. The pharmaceutical preparation of the present application satisfies the requirements of both easy swallowing and low gastric dissolution, and provides good compliance for patients with dysphagia and / or gastric disease.

The invention relates to the field of molecular biology and biological medicine, and particularly discloses a synergistic effect of combined application of Metrnl protein and a clinical first-line therapeutic drug clopidogrel for treating thrombus, and the Metrnl protein has important significance in the field of thrombotic disease treatment. According to the invention, mice are divided into four groups: a solvent control group, a Metrnl proteome, a clopidogrel group and a drug combination group. A FeCl3 induced thrombus experiment shows that thrombus formation can be inhibited by independently using Metrnl protein and clopidogrel, the thrombus formation inhibition effect is stronger by combined medication, and a synergistic effect is achieved. In addition, in the aspect of untoward effects of bleeding, compared with a clopidogrel single drug group, the risk of bleeding of the drug combination group is not obviously increased. The metrnl protein and clopidogrel are combined to enhance the antithrombotic curative effect without increasing the adverse reaction of bleeding, so that the metrnl protein and clopidogrel have good treatment potential and safety.

The invention discloses a liquid chromatography-tandem mass spectrometry detection method for clopidogrel and active metabolites thereof based on magnetic solid-phase extraction, which comprises the following steps: converting the active metabolites of clopidogrel into derivatives through derivatization treatment, and then detecting the derivatives. The detection targets of the method are clopidogrel and active metabolites thereof, the metabolic condition of clopidogrel in a human body can be effectively and truly reflected, and the method has important significance for monitoring the drug concentration of clopidogrel. According to the method, detection samples of clopidogrel and active metabolites thereof are pretreated through a magnetic solid-phase extraction technology, separation and transfer of to-be-detected substances can be rapidly achieved by applying an external magnetic field, automatic pretreatment can be achieved conveniently, and meanwhile the advantages of high specificity, high extraction rate and the like of solid-phase extraction are reserved; according to the sample treatment step, interference of substances such as endogenous phospholipids, proteins and salts can be removed, and the matrix effect and the pollution risk of a chromatographic column and a mass spectrometer are reduced.

The invention discloses a method for detecting impurities in clopidogrel aspirin tablets. Relates to the technical field of medicine. According to the detection method for the impurities in the clopidogrel aspirin tablets, the clopidogrel aspirin tablets are detected by adopting a high performance liquid chromatography, and the chromatographic conditions of the high performance liquid chromatography are as follows: a separation medium in a chromatographic column is octadecyl silica gel; the mobile phase comprises a sodium perchlorate buffer solution with the pH value of 2.0-3.0; the column temperature is less than 35 DEG C. According to the method for detecting the impurities in the clopidogrel and aspirin tablets, 13 impurities in a clopidogrel and aspirin tablet compound preparation can be detected at the same time.

The application provides a combined drug for improving embryo implantation efficiency of RIF patients and a screening method, and belongs to the technical field of embryo implantation. In order to solve the problem of how to screen a general drug combination on the basis of a large heterogeneous RIF population, the application locks 1119 kinds of drugs that may have a therapeutic effect in a large range through a six-step screening method combined with advanced RNA sequencing technology, and then further screens the drugs by using a highly simulated endometrial epithelial organoid and stromal cell model, tests the influence of the 1119 kinds of drugs on the activity of the endometrial epithelial organoid and stromal cell, and finally screens 7 kinds of effective drugs which can form a broad-spectrum drug with significant therapeutic effect on RIF in a combined form. The 7 kinds of effective drugs screened by the application are icotinib, fumaric acid propofol tenofovir tablets, clopidogrel, tizacat, osimertinib, venetoclax and rebastinib.

The invention discloses a clinical drug crowd reaction data arrangement and analysis system, which relates to the technical field of clinical drug crowd reaction data arrangement and comprises a data acquisition module, a data processing module, an arrangement module, a processing module and an analysis module. According to the method, the reactivity of the patient to clopidogrel can be accurately evaluated according to the multi-dimensional information of the patient by calculating the clopidogrel low reactivity index, a scientific basis is provided for timely adjusting a treatment scheme, the risk of adverse reactions such as bleeding is reduced, the risk degree of the adverse reactions can be calculated based on the multi-dimensional information of the patient, and the risk degree of the adverse reactions can be accurately evaluated according to the multi-dimensional information of the patient. The adverse reaction risk possibly occurring when the patient receives double-antibody treatment is predicted, a doctor can take preventive measures in advance, the adverse reaction occurrence rate of the patient is reduced, the treatment safety is improved, personalized pharmaceutical services can be provided according to the individual characteristics of the patient by calculating the medication evaluation index, and the clinical application prospect is wide. Therefore, individual requirements of the patient can be met, and the satisfaction degree and the treatment effect of the patient can be improved.

The invention discloses a pharmaceutical composition and application of the pharmaceutical composition in preparation of drugs for treating thrombotic diseases. The invention discovers that the composition formed by the dazoloxybenzene and the clopidogrel in the mass ratio of 1: 10-10: 1 has a remarkable antithrombotic effect, and the dazoloxybenzene and the clopidogrel generate a synergistic antithrombotic effect in the mass ratio of 1: 8-8: 1, so that an additional gain effect of 1 + 1 > 2 is achieved. Meanwhile, the composition formed by the dazoloxybenzene and the clopidogrel in a mass ratio of (1: 2)-(2: 1) can remarkably reduce the bleeding risk and has a synergistic effect. Therefore, the composition of the dazoloxybenzene and the clopidogrel, provided by the invention, has a prospect of being developed into an antithrombotic drug, and the bleeding risk is reduced while thrombus formation is inhibited.

The present invention provides a pharmaceutical composition comprising clopidogrel or pharmaceutically acceptable salts thereof; and tegoprazan or pharmaceutically acceptable salts thereof as an active ingredient. The pharmaceutical composition of the present invention has an advantage of maintaining a medicinal effect of clopidogrel while preventing or treating a side effect of clopidogrel, i.e., gastrointestinal disorders.

The invention provides a combined medicine for improving the embryo implantation efficiency of RIF patients and a screening method, and belongs to the technical field of embryo implantation. In order to solve the problem of how to screen general drug combinations on the basis of a huge heterogeneity RIF group, 1119 drugs which possibly have treatment effects are locked in a large range through a six-step screening method in combination with an advanced RNA (Ribonucleic Acid) sequencing technology; the method comprises the following steps: selecting 1119 types of medicines, then further utilizing a highly simulated endometrial epithelium organ and interstitial cell model to screen medicines, testing the influence of the 1119 types of medicines on the activity of the endometrial epithelium organ and interstitial cell, and finally screening 7 types of effective medicines to form a broad-spectrum medicine with a remarkable curative effect on RIF through a combination form. The seven effective drugs screened by the invention are respectively icotinib, a propofol fumarate tenofovir tablet, clopidogrel, tizacarbox, osimertinib, Vinetogram and ribotinib.

The invention relates to an application of clopidogrel in preparation of a medicine for preventing renal ischemia-reperfusion injury. The medicine is administrated 2 hours ahead of time, so that mouse kidney IRI can be prevented, and cell ferroptosis is inhibited through an FSP1 way. In-vitro cell experiments show that in various cell lines such as HT1080, HK2 and the like, clopidogrel can inhibit ferroptosis induced by ferroptosis inducers (such as RSL3, IKE, FIN56 or JKE-1674), and cell lipid peroxidation and intracellular Fe < 2 + > content increase caused by ferroptosis can be partially recovered. The clopidogrel disclosed by the invention has an obvious effect of inhibiting cell ferroptosis and is beneficial to prevention of renal ischemia reperfusion injury.