159 results about "Prasugrel" patented technology

The present invention is directed to pharmaceutical compositions comprising prasugrel and a cyclodextrin derivative, and methods of making and using the same.

A method for the prevention of diseases caused by thrombus or embolus. The method is to separately administer 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine or a pharmaceutically acceptable salt thereof, and aspirin, in their pharmacologically effective amounts, to a warm-blooded animal.

The invention relates to the technical field of a preparation method of an antithrombotic drug Prasugrel. The preparation method utilizes the existing cyclopropyl-2- fluoro-benzylone which is treated with enol esterification, oxidization, sulfonylation, condensation and synthesis to obtain the Prasugrel. Compared with the prior art, the preparation method provided by the invention has low toxicity in raw materials and reagents used, low requirements in labor protection, low prices of and easy access to raw materials and reagents, less emission of three wastes (waste gas, waste water and waste residues), less pollution to the environment and no corrosion to equipment during the production; simultaneously, the preparation method also has simple operation and greater yield compared with the prior art and is applicable to industrial mass production.

The invention discloses a new intermediate of Prasugrel, the structural formula of which is shown as the Fig; wherein, R represents alkyl. The invention can succinctly prepare a new intermediate of Prasugrel by utilizing existing industrial raw materials; the preparation of the Prasugrel by adopting the intermediate has mild reaction condition and prominent yield, but does not need low temperature and the adoption of flammable and combustible raw materials, thus being suitable for large-scale industrial production.

The present invention is directed to pharmaceutical compositions comprising prasugrel and a cyclodextrin derivative, and methods of making and using the same.

The invention relates to a Prasugrel hydrobromide tablet suitable for preparation by a direct compression process. In addition to containing the active component Prasugrel hydrobromide, the tablet also contains a filling agent, a disintegrating agent and a lubricant. And the tablet has the advantages of high dissolution rate, good stability, high safety, and simple preparation process.

The invention relates to a novel oral enteric preparation which is composed of 0.1-1000mg of Grel drugs, or medically acceptable salts, ester or derivatives, 37.5-325mg of aspirin and at least one medically acceptable load, wherein the Grel drugs, or medically acceptable salts, esters or derivatives are clopidogrel, prasugrel, brilinta, sarpogrelate, ozagrel, anagrelide, pamicogrel, or medically acceptable salts, ester or derivatives, preferably, clopidogrel sulfate. The oral enteric preparation is used for curing acute coronary syndrome (ACS), angor pectoris, stroke, myocardial infarction or cardia cerebrovascular diseases of patients. According to the oral enteric preparation, adverse reactions such as functional gastrointestinal disorders, nausea, vomit, gastritis, concealed hemorrhage, ulcer exacerbation and gastrointestinal bleeding caused by strong stimulus of aspirin to stomach can be avoided.

The invention provides a Prasugrel liposome solid preparation, which is characterized by being prepared by the following main components in parts by weight: 1 part of Prasugrel, 2-18 parts of yolk phosphatidylglycerol, 0.6-9 parts of cholesterol, 1.2-12 parts of sodium glycyl-cholate and 4-80 parts of other pharmaceutically accepted excipients. The Prasugrel liposome prepared by the invention has high entrapment rate and little side effect, improves stability of aqueous solubility thereof greatly and is favor of dissolving medicinal preparation out.

The invention relates to the technical field of a preparation method of an antithrombotic medicament Prasugrel. The preparation method condenses and synthesizes 2-cyclopropyl-1-(2-fluorophenyl)-2- carbonyl ethyl ester mesylate and 2-methoxyl-4, 5, 6, 7-tetrahydro-thieno (3, 2-c) pyridine to form the Prasugrel. Compared with the prior art, the preparation method provided by the invention has low toxicity in raw materials and reagents used, low requirements in labor protection, low prices of and easy access to raw materials and reagents, less emission of three wastes (waste gas, waste water andwaste residues) and no corrosion to equipment during the production; simultaneously, the preparation method also has tender reaction conditions, simple operation and greater yield compared with the prior art and is applicable to industrial mass production.

The invention discloses a new intermediate of Prasugrel, the structural formula of which is shown as the figure. The preparation of the Prasugrel by adopting the intermediate of the invention has mild reaction condition and higher yield than that of an existing preparation method, and is economical and effective, thus being suitable for large-scale industrial production.

An article of manufacture comprising packaging prasugrel tablets, caplets, capsule or other solid form of prasugrel in an air and / or moisture impervious container under a positive liquid gas pressure.

The invention provides a solid medicinal composition containing prasugrel bromate for treating thrombus. The composition has the advantages of good stability, convenient operation, transportation and storage, wide application range and suitability for scale production.

The invention mainly relates to prasugrel hydrobromide polymorph and a preparation method thereof.

Disclosed are improved processes for preparing prasugrel compound of formula-(1), its intermediates and pharmaceutically acceptable salts.

The invention relates to the technical field of an intermediate of an antithrombotic Prasugrel and a preparation method thereof. The intermediate is a compound of 1-cyclopropyl-2-(2- fluobenzene radical)-2-hydroxy butanone. Compared with the prior art, the method for preparing the Prasugrel by the intermediate has the advantages that the method adopts raw materials and agents which are easily obtained with low toxicity and price, and generates less three wastes; moreover, the operation is simple and the yield is higher. The method is suitable for industrialized production.

The invention relates to the technical field of an intermediate of antithrombotic drug prasugrel and a preparing method thereof. The intermediate for preparing the prasugrel has a structural format as the right, wherein R stands for alkyl or aryl. Compared with the prior method, the method for preparing the prasugrel by the drug intermediate has the advantages that both raw materials and reagents used by the method are low in cost and toxicity and can be easily obtained, the method generates less 'the three wastes', simultaneously has simple operation and higher yield, and applicability to industrial production.

The invention provides a cyclodextrin inclusion compound of prasugrel and acid addition salt thereof, which has stable inclusion structure, can be easily synthesized and saved and are stable in the air, and the water solubility of the prasugrel and the acid addition salt thereof is increased. The prasugrel and the acid addition salt thereof react with various cyclodextrins in water and organic solvents to prepare the stable inclusion compound which can be used as a therapeutic drug or has potential application.

The invention belongs to the field of chemical engineering and pharmacy, and relates to a method for synthesizing a prasugrel intermediate and a method for synthesizing prasugrel. The method for synthesizing the prasugrel intermediate comprises that: 2-bromine-1-cyclopropyl-2-(2-fluorophenyl) ethyl ketone and 2-ethylamine thiophene are condensated under the action of alkali; then, after the reactant reacts with formaldehyde, 1-cyclopropyl-2-(6,7-dihydro-thieno[3,2-c]pyridine-5(4H)-yl)-2-(2-fluorophenyl) ketone after cycization of protonic acid. The method for synthesizing the prasugrel by the intermediate comprises that: after the intermediate 1-cyclopropyl-2-(6,7-dihydro-thieno[3,2-c]pyridine-5(4H)-yl)-2-(2-fluorophenyl)ketone is oxidized, the reactant is esterified with acetic anhydride to obtain the prasugrel. Synthesis of the prasugrel by the method can obtain products with high yield and simple operation steps.

The invention provides a pharmaceutical composition containing active procyanidins and prasugrel or the pharmacologically acceptable salt thereof. The procyanidins and the prasugrel are used in a combined manner, a more effective method for curing thrombotic diseases is found, after trail for many times, the prasugrel and the procyanidins (an extract of traditional Chinese medicine) are creatively and effectively combined together, the effect of applying the procyanidins to inhibit the thrombosis in a combined manner is discovered unexpected in the process of applying the prasugrel to cure the thrombotic diseases, and not only the anticoagulant effect of the prasugrel is free from the influence of the procyanidins, but also a good effect is achieved in the aspect of reducing the adverse reaction of bleeding after the use of the prasugrel and the procyanidins in a combined manner, therefore, the risk of bleeding is greatly reduced when the advantages of good anticoagulant activity and fast effect of the prasugrel during the antiplatelet aggregation are fully exerted, the risk of bleeding of the prasugrel during the antiplatelet aggregation is effectively reduced and the adverse reaction of the prasugrel is greatly reduced.

The invention belongs to the field of pharmaceutical chemistry technology, and particularly discloses thienopyridine derivatives, and preparation methods and a medical use thereof. Through structural modification of clopidogrel and prasugrel, a series of new thienopyridine derivative compounds are synthesized and mainly include derivatives esterified with ligustrazine formic acid and shikimic acid; the compounds go into a body, then are rapidly metabolized into effective metabolites and ligustrazine formic acid or shikimic acid, successfully keep away from metabolism of CYP2C19 enzyme, can be directly metabolized into active compounds to play a pharmacological function, thereby solving the clopidogrel resistance problem, effectively improving the compound antithrombotic activity, and also having no significant effect on hemorrhage risk; and the compounds have relatively ideal protective function on liver and kidney, and also have potential therapeutic significance for other cardiovascular diseases.

The invention discloses a method for preparing prasugrel (I). The method comprises the following steps: performing addition reaction of a Grignard reagent prepared from fluorobenzyl bromide and cyclopropanecarbonitrile to obtain cyclopropyl-2-fluorobenzyl ketone; performing chlorination to obtain a main intermediate, namely alpha-cyclopropyl carbonyl-2-fluorobenzyl chloride (II); performing condensation reaction of (II) and 2-oxo-2,4,5,6,7,7alpha-hexahydrothieno[3,2-c]pyridine 4-methylbenzenesulfonate to obtain an intermediate, namely 5-(alpha-cyclopropyl carbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7alpha-hexahydrothieno[3,2-c]pyridine (IV); and performing acetic anhydride esterification on the (IV) to obtain the prasugrel (I).

The invention, belonging to the technical field of medicine, relates to a bi-functional anti-platelet aggregation medicine and an application of the medicine in preventing and treating arterial tlirombotic diseases. The medicine of the invention has both a P2Y12 receptor antagonist property and a phosphodiesterase inhibitory activity. The results of in vivo and in vitro anti-platelet aggregation activity experiments of the medicine provide the anti-platelet mechanism of the medicine, the structural formula and anti-platelet mechanism of the medicine are different from those of known anti-platelet medicines, aspirin, Clopidogrel, Prasugrel, Cilostazol, and platelet and fibrinogen receptor antagonist. The medicine of the invention has good inhibition effect to various platelet aggregation induced by agonists. The results of mice in vivo experiment models of arterial thrombosis show that the medicine of the invention has significantly similar antithrombotic activity with Clopidogrel and non-obvious side effect of hemorrhage. The medicine of the invention can be used as antithrombotic medications for treating coronary heart disease, apoplexy and other arterial tlirombotic diseases.

The invention relates to a prasugrel pamoate salt and a preparation method thereof. The prasugrel pamoate salt has a structure represented by the formula II, and has the advantages of good stability, low hygroscopicity, and high safety. Moreover, the preparation method has the advantages of simple operation and good repeatability. The provided prasugrel salt can be used as an anti-platelet drug.

The present invention relates to crystalline form I of Prasugrel hydrogensulfate. A process for the preparation of these salts, pharmaceutical compositions comprising the salts and the use of the salts as a pharmaceutical, in particular as a blood platelet aggregation inhibitor are also described. Seed crystals which can be employed in the above mentioned process as well as a process for their preparation are also disclosed.

Acid addition salts of 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine with sulfuric acid or sulfonic acids, pharmaceutical compositions comprising the same and processes for the production thereof. The acid addition salts have a low toxicity.

The invention belongs to the technical field of medicines, and specifically relates to prasugrel hydrobromide tablets and a preparation method thereof. The tablets and the preparation method are characterized in that: raw materials are pretreated or not pretreated before the preparation of the tablets, such that the raw materials contain a certain amount of an organic solvent; other auxiliary materials are added to the raw materials; and the materials are pressed into tablets, such that the prasugrel hydrobromide tablets are prepared. With the prasugrel hydrobromide tablets provided by the invention, the medicine stability is substantially improved, the dissolution rate and the bioavailability are good, and the adverse reaction of the medicine is reduced.

The invention relates to a synthetic method of prasugrel. 2-bromo-1-cyclopropyl-2-(2-fluorophenyl) acetone and 4,5,6,7-tetrahydro thieno [3,2-C] pyridine hydrochloride are condensed under the action of alkali, so that an intermediate, namely 1-cyclopropyl-2-(6,7-dihydro thieno [3,2-C] pyridine-5(4H)-yl)-2-(2-fluorophenyl) acetone, is obtained, and then oxidation and acylation are carried out, so that prasugrel is obtained. The synthetic method of prasugrel has the advantages that a prasugrel intermediate is synthesized, condensation yield is high, operating steps are simple, protection and deprotection steps in the prior art are eliminated, and cost is greatly saved.

The invention relates to Prasugrel salt and a preparation method thereof. The Prasugrel salt compound has a structure as formula II, wherein HA is acid, including cystine, asparagine, phenylalanine, threonine, tyrosine, glutamine, serine, methionine, tryptophane, valine, leucine, isoleucine, glycine, alanine and proline.

The invention discloses a prasugrel intermediate with a structural formula shown in the formula (I). The preparation method which uses the intermediate to prepare prasugrel is characterized in that the yield is high, the cost is low, the operation is simple, the method is suitable for mass production, etc. The invention also discloses a preparation method of the intermediate. The method comprises the steps of alkylation reaction, hydroboration reaction, deprotection reaction and coupling reaction. Compared with the prior art, the raw material for the preparation of the prasugrel intermediate is cheap and accessible; the process operation is simple, three wastes generated in the production process are less, the environmental protection pressure is low; and the yield is high, and the prasugrel intermediate is suitable for the industrial production.

The invention discloses a new method for preparing a Prasugrel intermediate alpha-cyclopropylcarbonyl-2-fluorobenzyl bromide which is a compound shown as a formula (III). In the method, a compound shown as a formula (I), namely cyclopropyl-2-fluorobenzyl ketone is taken as a raw material, and is bromized by a compound show as a formula (II), namely phenyltrimethylammonium tribromide to form the target product of alpha-cyclopropylcarbonyl-2-fluorobenzyl bromide, namely the compound in the formula (III). The method has the advantages of mild reaction conditions, high selectivity, high yield, low cost and environmental friendliness, and is suitable for large-scale industrial production.