292 results about "Clopidogrel" patented technology

The present invention relates to a method for preparing Clopidogrel and its derivatives. More particularly, the present invention is a method for preparation of (S)-2-Clopidogrel and its derivatives, which are active inhibitors of platelet aggregation, from an optically active (S)-2-chlorophenyl glycine alkyl ester through hydrolysis of racemic 2-chlorophenylglycine alkyl esters using an enzyme. The present invention employs a simple procedure to prepare Clopidogrel and its derivatives. Because no chiral resolving agents are used except for a small amount of enzyme, the cost of preparation can be reduced. In addition, the present invention is suitable for synthesizing highly optical-active Clopidogrel and its derivatives on a large scale by using optically active (S)-2-chlorophenylglycine alkyl ester obtained in high yield as an intermediate, and is also environmentally friendly since no highly toxic reagents are employed.

A process for producing enantiomerically enriched (S)-α-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5 (4H)-acetic acid hydrocarbyl ester, represented by the formula:

Is provided, wherein R¹ and R² are hydrogens and R³ is methyl (i.e., (S)-Clopidogrel). The process includes the steps of: (a) contacting N-2-chlorobenz-aldehyde-ylidene-1-ethylamine-2(2-thiophenyl)imine and an HCN source, in the presence of a non-metallic asymmetric Strecker catalyst to form enantiomerically enriched (S)-α,α-(2-thiophenylethylamino)(2-chlorophenyl)acetonitrile; (b) contacting the enantiomerically enriched (S)-α,α-(2-thiophenylethylamino)(2-chlorophenyl)acetonitrile and a formaldehyde equivalent, in the presence of an acid catalyst to form enantiomerically enriched α-5(4,5,6,7-tetrahydro[3,2-c]thienopyridyl)(2-chlorobenzyl)-nitrile; and (c) contacting the enantiomerically enriched α-5(4,5,6,7-tetrahydro[3,2-c]thienopyridyl)(2-chlorobenzyl)-nitrile and a reagent capable of converting a cyano group into an ester group to form enantiomerically enriched hydrocarbyl ester of (S)-α-(2-chlorophenyl)-6,7-dihydrothieno-[3,2-c]pyridine-5(4H)-acetic acid.

The invention provides a preparation method for clopidogrel and the salts of clopidogrel, belonging to the field of medical and chemical technology. The invention solves the problems of more reaction steps, long technical route, high cost and low purity of the existing preparation method for clopidogrel. The preparation method for clopidogrel comprises the following steps: a. synchronous resolution and racemization; b. preparation of (plus) alpha-(2 - thiophene triethylamine yl) -2 - (2 - chlorophenyl) methyl acetate; c. preparation of target product clopidogrel through cyclization reaction. The clopidogrel can generate medicinal salt with acids in a solvent. The preparation method for clopidogrel and the salts of clopidogrel has simple technology, easy operation, lower costs and higher product purity.

A pharmaceutical composition comprising a solid unit dosage form comprising: one or more of pharmaceutically active ingredients selected from valacyclovir, olanzapine, voriconazole, topotecan, artesunate, amodiaquine, guggulosterone, ramipril, telmisartan, tibolone, atorvastatin, simvastatin, amlodipine, ezetimibe, fenofibrate, tacrolimus, valgancyclovir, valsartan, clopidrogel, estradiol, trenbolone, efavirenz, metformin, pseudoephedrine, verapamil, felodipine, valproic acid/sodium valproate, mesalamine, hydrochlorothiazide, levosulpiride, nelfinavir, cefixime and cefpodoxime proxetil in combination with a water insoluble polymer and/or a water soluble polymer. Methods for making the pharmaceutical composition are also disclosed.

The invention relates to the clopidogrel solid preparation and the preparation method thereof, which belong to the medicine field. The invention solves the technical problem of preventing the dextro isomer of clopidogrel from transforming into laevo isomer, and preventing clopidogrel from degrading into clopidogrel acid. Concretely, clopidogrel or derivatives thereof and Beta-cyclodextrin are mixed and sieved, so as to prepare the clopidogrel solid preparation through the conventional solid preparation method. Beta-cyclodextrin used as principle medicine wrapping agent can effectively prevent the degrading problem of clopidogrel sulphate, and improve the stability of dextro isomer of clopidogrel sulphate. The result of stability experiment indicates that the clopidogrel laevo isomer and clopidogrel acid are not obviously increased when the clopidogrel solid preparation is stored for long time or used in an accelerated test process so that the clopidogrel solid preparation has good stability and safe clinical application.

The invention lies in the area of platelet function diagnostics and relates to an in vitro method for the determination of platelet function under flow conditions. The method is particularly suitable for the determination of the effect of clopidogrel after oral intake and of other P2Y(12) antagonists with antithrombotic activity as well as the determination of P2Y(1) receptor antagonists with antithrombotic activity.

Provided is clopidogrel base suitable for pharmaceutical formulation, and processes for its preparation.

The present invention provides one kind of compound with anticoagulant effect, and is especially new preparation process of clopidogrel and its pharmaceutical salt. The preparation process includes the following four steps: 1. resolving recemized methyl o-chlorophenyl glycinate to obtain (+)-methyl o-chlorophenyl glycinate and (-)-methyl o-chlorophenyl glycinate; 2. recemizing (-)-methyl o-chlorophenyl glycinate to obtain recemized (-)-methyl o-chlorophenyl glycinate; 3. repeating the steps 1 and 2; and 4. preparing clopidogrel with (+)-methyl o-chlorophenyl glycinate obtained in the step 1 and preparing the obtained clopidogrel into corresponding salt. The process of the present invention has simple path, short circulating period, low cost, high product purity, less toxic side effect and corrosion to the production apparatus.

Provided are crystalline forms of clopidogrel hydrobromide and processes for their preparation.

The invention provides an automatic issuing system of clopidogrel medication related gene test reports. Each test report contains much information like basic information of a patient, test result, test conclusion and personalized medication suggestion, the system can effectively integrate and display the much information in a centralized manner, and the personalized medication suggestion portion can be directly applied mechanically after being edited in a unified manner and can be added with personalized remark information; the test reports can be issued quickly, efficiently and accurately according to results of genotype of related genes (CYP 2C19, PON1 and ABCB1 genes) on a gene testing instrument even if there are many testing cases, and the system can automatically issue the test reports as long as the patients input basic clinical information and gene testing results. Consumption of a lot of manpower when issuing troublesome reports is avoided, a lot of time cost can be saved, anderror rate during report issuing can be lowered, so that the system is convenient for medical staff to use in clinical work.

The invention relates to a sustained-release preparation of a compound composite, in particular to a compound sustained-release preparation of aspirin and clopidogrel or an pharmaceutically acceptable salt thereof, comprising a basic remedy, an auxiliary material with sustained-release function and other auxiliary materials, wherein the mass ratio of the basic remedy to the auxiliary material with the sustained-release function is 1:0.01-1:20, and the mass ratio of the aspirin to the clopidogrel or the acceptable salt thereof is 0.1:1-10:1. The compound composite is used for preventing and treating diseases caused by platelet aggregation, and the sustained-release preparation prepared by the compound composite can reduce stimulation effect of medicaments on the gastrointestinal tract, improves patient compliance, avoids peak valley phenomenon in the blood after common preparations are taken, lowers the occurrence of adverse reaction, and enhances medication safety and curative effect, thereby achieving stable effects with sustainable action.

The present invention discloses a method for preparing I-type clopidogrel hydrosulfate. Said method includes the following steps: a), oblaining clopidogrel free alkali; b), adding ketone solvent into clopidogrel free alkali, and drop-adding sulfuric acid, after the drop-adding process is completed, heating to 20-50deg.C, heat-insulating and stirring, filtering and washing, vacuum drying wet product at 50-55deg.C so as to obtain the invented I-type clopidogrel hydrosulfate. The described ketone solvent is selected from five-carbon ketone or six0carbon ketone.

The invention relates to a method for preparing clopidogrel. The conventional synthetic methods have the disadvantages of poor environmental protection, disadvantageous industrial production, low optical purity of final products and high cost. The technical scheme adopted by the invention comprises the following steps of: performing a reaction on a compound, namely, R,S-o-chloromandelic acid and methanol to produce R,S-chloromandelic acid methyl ester; performing the reaction on the R,S-chloromandelic acid methyl ester and benzene sulfonyl chloride under the action of an alkaline catalyst to produce 2-benzenesulfonic acyloxy-2(2-chlorphenyl) methyl acetate; performing an SN2 substitution reaction on the 2-benzenesulfonic acyloxy-2(2-chlorphenyl) methyl acetate and 4,5,6,7-tetrahydro-thiophene pyridine hydrochloride under an alkaline condition to produce R,S-clopidogrel free alkali; resolving the R,S-clopidogrel free alkali in resolving solvent by using a resolving agent; and dissociating the resolved R,S-clopidogrel free alkali to prepare the clopidogrel. In a synthetic route of the invention, reaction conditions are temperate, used reaction substrates are environmentally friendly, reaction yield in each step is high, the optical purity of a final product is up to over 99.5 percent, and pollution-free production can be realized.

The invention belongs to the technical field of biology, and particularly relates to a kit for detecting efficient typing of gene loci related to clopidogrel drug resistance reaction. The kit is based on a Sequenom MassARRAY typing system, and comprises PCR (polymerase chain reaction) amplification primers and single-base extension primers of gene loci CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893). The sequences of the PCR amplification primers of gene loci are respectively disclosed as SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3 and SEQ ID NO.4. The sequences of the single-base extension primers of gene loci are respectively disclosed as SEQ ID NO.5 and SEQ ID NO.6. Before the subject takes clopidogrel, whether the gene loci of the subject are mutated is detected to instruct the individualized reasonable application of the subject, thereby providing references for individualized antiplatelet therapy.

The invention provides an optically active 2-hydroxyltetrahydrothienopyridine derivative shown by formula I, or a pharmaceutically acceptable salt, solvate, polycrystal, enantiomer or racemization mixture thereof, wherein in the formula I, R1 is F, Cl, Br or I; m is 0 or 1; n is an integer from 1 to 6; R2 or R3 is independently hydrogen, C1-C6 alkyl or optionally substituted C1-6 alkyl; R4 or R5 is independently hydrogen, C1-C10 alkyl, C1-C10 alkenyl, C1-10 alkoxy, C1-10 aryl, halogen, acylamino, sulfmidyl, acyloxy or C(O)R', and R' is hydrogen, C1-C10 alkyl, C1-C10 alkenyl, C1-10 alkoxy, C1-10 aryl, halogen, acylamino, sulfmidyl or acyloxy. The compound has obvious platelet agglomeration resistance action, and the bioavailability of the compound is obviously higher than that of clopidogrel. The invention further provides a preparation method of the compound, a pharmaceutical composition containing the compound, and a pharmaceutical use of the compound and the pharmaceutical composition.

The invention discloses a kit used for detecting the polymorphism of genes related to Warfarin and Clopidogrel personalized medication and application thereof. The kit comprises a general chip, a first primer combination and a second primer combination, wherein each primer combination unit in the first primer combination is used for identifying one polymorphism site of the genes related to Warfarin medicine resistance, and each primer combination unit in the second primer combination is used for identifying one polymorphism site of the genes related to Clopidogrel medicine resistance. The kit has the advantages of being high in integration degree, sensitivity, specificity, reliability and operability and wide in application range, detection results are stable, a use method is fast and convenient, and automation of the kit is easy to achieve; the kit can be used for detecting gene mutation, analyzing gene polymorphism and the like and is suitable for gene analysis fields such as mutation detection of clinical diseases, pharmacogenomics analysis and medicolegal expertise.