15 results about "Dabigatran" patented technology

The invention provides application of an SNP (Single Nucleotide Polymorphism) marker of MIA2 in predicting the curative effect of an antithrombotic drug on thrombus, and belongs to the fields of molecular biology and cardiovascular medicine. According to the application disclosed by the invention, one or more of rs11845046 and rs10134365 of the MIA2 gene is found to be related to the prediction of the curative effect of dabigatran on thrombus for the first time. Gene polymorphism analysis and an ROC curve verify that the curative effect of an NVAF patient after the NVAF patient is treated by using the antithrombotic drug is related to the genotypes of rs11845046 and rs10134365 of the MIA2 gene in a patient sample, and when the genotype of the rs11845046 is GG or the genotype of the rs10134365 is CC, the drug effect of the subject taking the antithrombotic drug is good but the probability of bleeding events is increased.

The application discloses a kind of dabigatran bleeding risk prediction methods based on machine learning, it is related to computer-aided drug risk management technical field, the method is by obtaining patient baseline and follow-up data, multiple imputation method is handled missing value;With HAS-BLED score as the basis, candidate variables are screened from potential risk factors using LassoCV algorithm, and anemia, insulin use and antifungal agent use are determined as new prediction variables through clinical correlation analysis to construct a set of prediction variables;Finally, a random forest or gradient boosting algorithm is used to train the model to output the bleeding risk assessment results of the individual to be tested.The application combines machine learning algorithm, improves the prediction accuracy of dabigatran bleeding risk in Chinese non-valvular atrial fibrillation patients, solves the problem of insufficient prediction accuracy of traditional HAS-BLED score, and provides a more reliable basis for clinical individualized anticoagulant therapy decision.

The application discloses application of a dabigatran chlorine-containing derivative in preparation of a medicine for inhibiting and treating colon cancer, and a structure of the compound is: the compound is an artificial synthetic compound, and experiments by MTT colorimetry prove that the compound with an amount greater than 12.5 mu g / mL can effectively inhibit HCT116 colon cancer cell activity, and the greater the amount of the compound, the more significant the inhibiting effect on HCT116 cells is, and the compound can be used for research on human colon cancer as a medicine for inhibiting proliferation of human colon cancer cells or an antitumor medicine.

This invention relates to the field of pharmaceutical intermediates, and in particular to a method for synthesizing dabigatran ester intermediates. The synthetic route includes the following steps: (1) reacting compound V with compound IV in the presence of a condensing agent to obtain compound III; (2) reacting compound III with compound II in the presence of a base to obtain compound I. This invention improves upon the traditional synthetic route for dabigatran ester intermediates. The method features mild reaction conditions, simple operation, and high yield and purity, making it suitable for large-scale industrial production.

The invention discloses a preparation method of a dabigatran etexilate precursor, and belongs to the technical field of drug intermediate synthesis. The method comprises the following steps: S1, under the protection of nitrogen, reducing nitro of a compound IV into amino by taking tetrahydroxy diboron and 4, 4 '-dipyridyl as a concerted catalytic system, and purifying to obtain a compound III; s2, pretreating a compound III, a compound II and a condensing agent, performing low-temperature activation and microwave reaction in a DMF / DCM mixed solvent in the presence of HATU, HOAt and DIPEA, and performing post-treatment and recrystallization to obtain an amino amide intermediate; and S3, dissolving the amino amide intermediate in glacial acetic acid, carrying out reflux cyclization, and carrying out post-treatment and recrystallization to obtain a compound I. According to the invention, tetrahydroxy diboron and 4, 4 '-dipyridyl are adopted to synergistically catalyze nitro reduction, the conditions are mild, and the reaction is rapid; by means of synergistic catalysis of HATU and HOAt, water removal through a 4molecular sieve, batch addition of HATU, microwave assistance and the like, the reaction time is shortened, the yield is increased, side reactions are reduced, and the method is suitable for industrial production.

The invention relates to the field of effective and economical conversion of nitro or nitroso compounds in to corresponding amines. More it discloses a reduction processes of nitro or nitroso compounds to corresponding amino compounds, which exhibit differential solubility, exemplified & not restricted to the processes discussed for m-aminoacetophenone, the intermediate of Phenylephrine, ethyl3- [[4-(methylamino)-3-aminobenzoyl](pyridin2yl)amino]propanoate the intermediate of Dabigatran, and 2,4-Difluoroaniline the intermediate of Pantoprazole. Even more particularly, the invention relates to a process involving use of minimal quantity of water or quantity of water required only as the source of hydrogen for generation of sufficient reduction potential to perform the chemical reaction. The process offers a. safer, cost competitive and greener alternative to the conventional process of reduction. A key benefit of the invention is that it avoids side product / s & / or impurity / s resulting from usage of large quantity of water especially when other sensitive / reactive groups are present in the molecule.

Relacorilant is a selective modulator of the type II glucocorticoid receptor (GR); it may be orally administered. Applicant discloses in vitro studies that show relacorilant to be a potent inhibitor of P-glycoprotein (P-gp). Surprisingly, in vivo studies of co-administration of relacorilant and dabigatran etexilate (a P-gp substrate) showed that relacorilant had minimal-to-no impact on the free and total dabigatran plasma exposures, suggesting that only minimal or no dose adjustments are needed for P-gp substrates upon coadministration with relacorilant. The surprising finding that relacorilant may be safely co-administered with P-gp substrates without need for significant dose adjustment provides improved methods and uses for treatment of such disorders as, for example, hypercortisolism (e.g., Cushing's syndrome, Cushing's Disease), hyperglycemia, hypertension, and a solid tumor in combination with chemotherapy or immunotherapy agents.

A computer implemented method for determining a dosage of dabigatran for administering to a patient, the method comprising: receiving patient data relating to a patient, wherein the patient data includes a kidney function metric; processing the patient data with a dosage calculator to determine the dosage of dabigatran for administering to the patient, wherein the dosage calculator is derived from a plasma level prediction model; and indicating the dosage.

According to the preparation method of the key intermediate N-(4-cyanophenyl) glycine of dabigatran etexilate, p-chlorobenzonitrile and glycine serve as raw materials, a target compound (I) is obtained through one step, the raw materials are easy to obtain and low in price, reaction conditions are mild, the yield is high, water serves as a reaction solvent, emission of three wastes is remarkably reduced, and the method is environmentally friendly and more friendly, and has good industrial application prospects. The method is suitable for large-scale commercial production.

The present invention discloses a dabigatran etexilate pamolate compound, its preparation and use, belonging to the field of pharmaceutical technology. The present invention provides a novel salt compound of dabigatran etexilate shown in formula (I). After forming a salt of dabigatran etexilate with pamolic acid, it can effectively improve solubility and stability under influencing factors, which is beneficial to further study the medicinal route and administration method of dabigatran etexilate in the future, improve the pharmacological effect and reduce the adverse reactions of the drug.

This invention relates to the field of pharmaceutical intermediates, and in particular to a microchannel method for preparing dabigatran ester intermediates. The synthetic route of this invention utilizes a continuous flow microchannel reactor in the preparation of dabigatran ester intermediates, thereby significantly shortening the reaction time to within a few hundred seconds. Simultaneously, the target product obtained through this continuous flow reaction process exhibits high yield and high purity; testing shows that the purity of the target product can reach over 99%, and the yield can reach over 90%. The preparation method of this invention produces few byproducts, can be continuously produced, and has a high degree of automation, showing promising prospects for industrial application.

The invention discloses a preparation method of a dabigatran nitroso impurity, which comprises the following steps: (1) dissolving a raw material (A) in a solvent, adding alkali, then adding an amino protecting group raw material and a catalyst, and reacting to obtain an intermediate product (B); (2) dissolving (B) in a solvent, then adding a nitrosation reagent, and carrying out nitrosation reaction to obtain an intermediate product (C); (3) dissolving (C) in a solvent, and removing a terminal amino protecting group R to obtain an intermediate product (D); and (4) dissolving (D) in a solvent, adding alkali, and carrying out ester hydrolysis reaction to obtain a target product (E). The target product is obtained through four-step reaction, the reaction condition is mild, the chemical purity of the product can reach 98% or above, a reference substance is provided for qualitative and quantitative analysis of dabigatran drugs, meanwhile, an important basis is provided for scientific evaluation of quality, safety and efficiency of dabigatran, and important application value is achieved.

The invention discloses a pellet of dabigatran etexilate or pharmaceutically acceptable salt thereof, which comprises a pellet core, a drug layer containing dabigatran etexilate or pharmaceutically acceptable salt thereof and a protective layer, and the drug layer containing dabigatran etexilate or pharmaceutically acceptable salt thereof is located between the pellet core and the protective layer. And the protective layer contains a water-soluble polymer and a water-insoluble cellulose derivative having a bonded hydrophobic group, the weight ratio of the water-soluble polymer to the water-insoluble cellulose derivative having a bonded hydrophobic group being 0.67: 1 to 1.3: 1. Compared with the prior art, the risk of adhesion of the pellets in the capsule is reduced, so that the effects of reducing drug administration individual variability, stably releasing organic acids and drugs, improving bioavailability and reducing side effects are achieved.

The present invention provides an oral pharmaceutical composition and a usage thereof, comprising a pharmaceutically acceptable acidic medicinal auxiliary material whose surface is modified and dabigatran etexilate or pharmaceutically acceptable salts or aquo-complexes thereof. The present invention further provides a surface modification method for a medicinal auxiliary material.