172 results about "Dabigatran" patented technology

The invention relates to dabigatran ester derivatives as shown in a constitutional formula I, pharmaceutically acceptable nontoxic salts thereof, medical composite containing the compounds as active components, and application of thrombin inhibitor of the compounds and medical composites, wherein R1 represents H or C1 to C5 alkyl; R2 represents H, or C1 to C3 alkyl; and R3 represents C1 to C8 alkyl or substituted alkyl.

The invention discloses a pharmaceutical composition containing dabigatran etexilate or salt and hydrate of the dabigatran etexilate. The pharmaceutical composition comprises an active substance pill core material containing the dabigatran etexilate or its pharmaceutically acceptable salt or hydrate and a filling agent and / or a bonding agent,and an organic acid or an organic acid material layer, the organic acid is arranged outside the active substance pill core materials, the organic acid material layer contains the organic acid, and the organic acid is selected from tartaric acid, succinic acid, citric acid, glutamic acid, fumaric acid, malic acid, aspartic acid or their hydrates or salts. After screening, the dabigatran etexilate active substance is prepared into a pill core, the organic acid material layer is added in an integrated mode, and meanwhile, an isolated layer is applied between the dabigatran etexilate active substance pill core and the organic acid material layer. The prepared dabigatran etexilate oral drugs composition has the advantages that solubility and dissolution rate are good, and bioavailability effect is prominent.

The invention provides a dabigatran etexilate malate having a general formula shown in the specification, and a hydrate and/or solvate thereof. In the formula, n is 1, 2 or 3. The invention also provides a preparation method of the dabigatran etexilate malate, the hydrate and/or solvate thereof, and an application in the preparation of medicines for treating or preventing cardiovascular diseases.

The invention discloses a method for preparing and purifying a dabigatran etexilate key intermediate 3-{2-[(4-cyanoanilino)methyl]-1-methyl-benzimidazolyl-5-[N-(2-pyridyl)formamido]}-ethyl propionate (I). The preparation process comprises the following steps: reacting 2-( 4-cyanoanilino)acetic acid (IV) and 3-[4-methylamino-3-amino-N-(2-pyridyl)-benzamido-]-ethyl acrylate (III) in the presence of a condensing agent to form a condensate; and carrying out cyclization reaction under the catalytic action of acetic acid to prepare the 3-{2-[(4-cyanoanilino)methyl]-1-methyl-benzimidazolyl-5-[N-(2-pyridyl)formamido]}-ethyl propionate (I). The purification process comprises the following steps: reacting the compound (I) and succinic acid to form 3-{2-[(4-cyanoanilino)methyl]-1-methyl-benzimidazolyl-5-[N-(2-pyridyl)formamido]}-ethyl propionate succinate (V), and finally, adding alkali for dissociation to obtain the high-purity compound (I).

Compositions comprising a mixture of at least two types of particles wherein a) the first type of particles comprise dabigatran etexilate in the form of the free base or in the form of pharmaceutically acceptable salts, polymorphs, solvates or hydrates thereof; and b) the second type of particles comprise at least one pharmaceutically acceptable organic acid, use of said compositions in the reduction of the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation and/or in the prevention of venous thromboembolic events in adult patients who have undergone elective total hip replacement surgery or total knee replacement surgery and processes for the preparation of said compositions.

The present invention relates to antibody molecules against anticoagulants, in particular dabigatran, and their use as antidotes of such anticoagulants.

The present invention relates to an oral pharmaceutical composition comprising dabigatran etexilate or a pharmaceutically acceptable salt thereof, methods for preparing it and dosage forms for oral administration comprising said composition. The pharmaceutical composition is particularly useful as a medicament, especially as anticoagulant.

The invention relates to a dispersion preparation containing dabigatran etexilate. The dispersion preparation mainly comprises a dispersible tablet containing an active substance dabigatran etexilate, and a dispersed particle capsule. The preparation has the characteristics that the preparation can be disintegrated into fine particles in water within three minutes and a uniform suspension is formed. The particles can be evenly distributed and can pass through a 2# sieve (24 meshes). The dissolution rate and the absorption rate of the medicines can be significantly increased after the medicines with poor water solubility are prepared into the dispersion preparation, and the bioavailability is also improved. Meanwhile, the dispersion preparation has the advantages of being convenient to swallow, simple in production technology, high in reproducibility, high in medicine loading rate, easy to divide the dose and the like, and does not change the pH of gastric juice of a sufferer.

The invention belongs to the technical field of Dabigatran etexilate preparation method. The invention provides a novel compound represented by the formula 4. A preparation method of the compound is simple, and reaction conditions are mild. With the compound represented by the formula 4, a target compound Dabigatran etexilate can be obtained with two-step reactions and with high yield. Compared with prior arts, the prices of reagents adopted by the preparation method are cheap, reaction times in the steps are short, the yield is high, the conditions are mild, and intermediate purification is convenient. The method provided by the invention is a good method for preparing Dabigatran etexilate with high yield and low cost.

The invention discloses Dabigatran etexilate benzene sulfonate as well as a preparation method and application thereof. The Dabigatran etexilate benzene sulfonate has a structure shown in a formula I in the specification. According to the Dabigatran etexilate benzene sulfonate, the active substance Dabigatran etexilate is salified to change the physical and chemical properties of the active substance, and then effect of a medicament is significantly improved under the condition without pharmacokinetic differences, so that the Dabigatran etexilate benzene sulfonate has a wide prospect in the aspect of preparing an anticoagulant medicament.

The invention provides a dabigatran etexilate derivative shown as a formula I, or pharmaceutically acceptable salt, a solvate, a polymorph, an antipode or a racemic mixture thereof. In the formula I, R1 is hydrogen or C1 to C5 alkyl, R2 is shown in the specifications, R3 and R4 are independently hydrogen or C1 to C5 alkyl, n is 0 or 1, and R5 is C1 to C8 alkyl or optionally substituted C1 to C8 alkyl. The compound has the activity of a thrombin inhibitor. The invention also provides a preparation method for the compound, a compound-containing medical composition, and application of the compound and the medicinal composition to preparation of thrombin inhibitor medicines and treatment of related diseases.

The invention relates to a method for preparing Dabigatran etexilate. The method comprises the specific steps of enabling a compound represented by a formula 1 shown in the description, i.e., 3-[[[2-[[(4-cyanophenyl)amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl] pyrid-2-ylamino]ethyl propionate to subject to addition reaction with hydroxylamine hydrochloride in the presence of a catalyst in an alcoholic solution, so as to obtain a compound represented by a formula 2 shown in the description, reducing the compound represented by the formula 2 so as to obtain a compound represented by a formula 3 shown in the description, and enabling the compound represented by the formula 3 to subject to amidation reaction with n-hexyl chloroformate in the presence of a catalyst, thereby obtaining a compound represented by a formula 4 shown in the description, i.e., Dabigatran etexilate. Compared with the prior art, the preparation process disclosed by the invention has the advantages that the generation of a large volume of waste acid in the prior art is avoided, the reaction conditions are mild, the control is easy, the yield is high, and the product quality is good, thereby being applicable to industrial production.

The invention discloses a dabigatran etexilate analogue with fluorine-containing group modified pyridine ring as a center and a synthesis method of the analogue. According to the synthesis method, with a fluorine-containing group aminopyridine compound as a starting material, a series of reactions are carried out to prepare he fluorine-containing group modified dabigatran etexilate analogue. The synthesis method of the analogue has the advantages that the operation is simple, used reagents are low in cost and easily available, synthesis cost is relatively low, rick in the synthetic process is low, yield of each synthesis step is high, and synthesis time is short.

The invention relates to a method for treating an overdosing with active substance dabigatran etexilate of formula I

optionally in the form of the pharmaceutically acceptable salts thereof, comprising the administration of an effective amount of charcoal.

The invention relates to a method for detecting organic-solvent residues in dabigatran etexilate, and particularly relates to a method for simultaneously detecting residues of alcohol, acetone, ethyl acetate and tetrahydrofuran in dabigatran etexilate by gas chromatography. An external standard method is adopted for simultaneously detecting the amount of the residues of four types of organic solvents in the dabigatran etexilate, and the chromatographic conditions are as follows: a chromatographic column is in the type of Agilent DB-1301 (30m*0.32mm*0.25microns), the column temperature is increased by programming, the initial temperature is 40 DEG C, the maintaining time is 6 minutes, then the temperature is increased to be 180 DEG C at a speed of 50 DEG C/min and is maintained for 10 minutes, the temperature of a sample inlet is 200 DEG C, the detection temperature is 250 DEG C, carrier gas is N2, the flow is 2ml/min, a headspace sampling method is adopted, the balance time is 30 minutes and the balance temperature is 90 DEG C. The method is high in sensitivity, good in repeatability and high in accuracy, and is suitable for detecting the organic-solvent residues in the dabigatran etexilate.

The invention belongs to the technical field of medicinal chemistry and particularly relates to a preparation method for a dabigatran etexilate intermediate cyclocompound. The preparation method comprises the following steps: adding ((4-cyanophenyl) phenyl) glycine (II)), carbonyldimidazole (III) and a first solvent into a reaction bottle, and rising the temperature to T1 to perform first reaction for t1; then, adding 3-((3-amino-4-methylaminobenzoyl) pyridin-2-ylamino) propionic acid ethyl ester (IV),and rising the temperature to T2 to continuously perform second reaction for t2; rising the temperature to T3 to continuously perform third reaction for t3; and evaporating off the first solvent to obtain a cyclocompound crude product, and adding a second solvent to perform recrystallization and refining so as to obtain the dabigatran etexilate intermediate cyclocompound (I). The preparation method is stable in process, simple to operate, strong in operability and suitable for industrial production.

The invention discloses a compound shown as formula (II), a hydrate, isomer, solvate, prodrug or a mixture thereof, and pharmaceutically acceptable salts thereof. The invention also discloses a pharmaceutical composition and a combination preparation containing the compounds as active ingredients, and use of the compounds, the pharmaceutical composition and the combination preparation as thrombininhibitors.