52 results about "Ozagrel" patented technology

The invention relates to an ozagrel sodium injection and a preparation method thereof, in particular to an ozagrel sodium injection for treating acute thrombotic cerebral infarction and movement disorders concomitant with cerebral infarction, preferably injection solution and lyophilized powder injection. The ozagrel sodium injection mainly comprises ozagrel serving as an active component and sodium hydroxide and citric acid serving as auxiliary materials. Solvent in the injection solution is water for injection. Excipient in the lyophilized powder injection is mannitol and/or sorbitol which can be combined in any one or two optional medicinal proportions, or no excipient is added.

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 relates to a high-purity ozagrel compound, and a preparation method of the ozagrel compound guarantees the quality of raw materials, and avoids the phenomenon that visible foreign matters are unqualified in the production process. The preparation method includes the following steps: (1) adding crude ozagrel in water to form aqueous dispersion; (2) then dropwise adding sodium hydroxide solution in the aqueous dispersion until the aqueous dispersion is clear to obtain clear solution; and (3) adding activated carbon in the clear solution for adsorption, conducting filtering and decarburization, adding acid in obtained filtrate to adjust pH value, precipitating solids, filtering, washing, and drying to obtain the high-purity ozagrel.

The invention provides an ozagrel salt which is stable, has functions of inhibiting platelet aggregation and removing blood-vessel convulsion, has good water solubility, and is prepared into a compound suitable for clinical application. The new compound is ozagrel tromethamine; and the ozagrel and the tromethamine are prepared by reaction in a solvent. The compound has good water solubility, strong and long-term stability, and the functions of inhibiting platelet aggregation and removing blood-vessel convulsion.

The invention discloses a preparation method of Ozagrel sodium. The method comprises the following steps: performing a bromination reaction on ethyl 4-methylcinnamate and N-bromo-succinimide by takingacetonitrile as a solvent under the triggering of azodiisobutyronitrile, so as to obtain ethyl 4-bromomethylcinnamate; performing a condensation cyclization reaction on the ethyl 4-bromomethylcinnamate and imidazole by taking sodium hydroxide as an acid-binding agent and taking tetrahydrofuran as a solvent, so as to obtain imidazole ethyl 4-methylcinnamate; performing alkali hydrolysis on the imidazole ethyl 4-methylcinnamate, so as to obtain the Ozagrel sodium. According to the preparation method, the condensation cyclization reaction is performed by taking the sodium hydroxide as the acid-binding agent and taking the tetrahydrofuran as the solvent, so that the finally obtained product does not contain toxic components, the yield and the purity of the product can be effectively improved,and the content of genotoxic impurities (the ethyl 4-bromomethylcinnamate and ethyl 4-dibromomethylcinnamate) in the product is zero.

The invention discloses a method for preparing an ozagrel intermediate (E)-4-(methyl imidazolyl) methyl cinnamate, which comprises the following steps of: (1) sodium imidazolide preparation: (1.1) dissolving sodium hydroxides in deionized water, and after the sodium hydroxides is completely dissolved, stirring the obtained product and adding imidazolide to the obtained product; (1.2) putting the solution obtained in the step (1.1) into a reaction kettle and uniformly mixing to obtain a stand-by material; and (1.3) adding toluene to the stand-by material obtained in the step (1.2), then adding acetone to the obtained mixture to obtain an acetone solution; and (2) (E)-4-(imidazolyl-methyl) methyl cinnamate preparation: (2.1) adding methyl 3-(4-bromomethyl) cinnamate to the acetone solution, and after reaction, carrying out depressurized evaporation on the obtained product to remove acetone from the material; and (2.2) adding deionized water to the material subjected to acetone evaporation in the step (2.1), and stirring the obtained mixture to crystallize, thereby obtaining the (E)-4-(imidazolyl-methyl) methyl cinnamate. By using the method disclosed by the invention, the shortages existing in the prior art can be overcome, and the production cost of the intermediate is greatly reduced.

The invention discloses an ozagrel ester with the compounds of the ozagrel ester. The ozagrel ester is provided with a chemical structural formula as listed on the right. The compounds of the ozagrel ester comprise an ozagrel ester with the amount of effective treatment and a carrier accepted in medicine. The invention also discloses the preparation methods for the ozagrel ester and the compounds of the ozagrel ester. The ozagrel ester of the invention has good solubility and stability; besides, the compounds of ozagrel ester can be conveniently made into a plurality of liquid, solid, freeze-drying and mucosa or the skin medication agents.

The present invention relates to a more stable sodium ozagrel compound and a pharmaceutical composition, which comprises recrystallizing the crude product sodium ozagrel with ethyl acetate:methanol=1:1 as a solvent for 1-3 times, and simultaneously using activated carbon White crystals are obtained after decolorization.

The invention discloses an ozagrel sodium drug combination for injection. The ozagrel sodium injection solution consists of ozagrel sodium, mannitol and anhydrous sodium carbonate, wherein each piece contains 20-80 mg of ozagrel sodium, 20-80 mg of mannitol and 5-15 mg of anhydrous sodium carbonate. The drug combination is prepared by a method comprising the following steps: taking a recipe quantity of injection water, adding the mannitol and the anhydrous sodium carbonate and stirring until the mannitol and the anhydrous sodium carbonate are dissolved; adding the ozagrel sodium, and stirring until the ozagrel sodium is fully dissolved; regulating a pH value between 7.7 and 8.7; adding medicinal carbon and stirring; leaching, replenishing the injection water to a full quantity and uniformly mixing; finely filtering; encapsulating; freeze-drying; inspecting with a light; and warehousing to obtain the ozagrel sodium drug combination. The ozagrel sodium drug combination has good stability. The production rate of the product is increased, the cost is lowered, and industrialization is realized. The drug combination can be better applied in clinic and has more remarkable advantages.

The invention belongs to the technical field of medicines, and particularly relates to an ozagrel compound, a preparation method and a pharmaceutical composition of the ozagrel compound. The X-ray powder diffraction spectrogram obtained by Cu-K alpha-ray measurement is shown in a figure 1; and the structural formula is as shown in a formula (I). The ozagrel compound is a novel crystal form which is different from that in the prior art. The novel crystal form ozagrel compound has humidity, temperature and illumination stability obviously superior to those of the ozagrel in the prior art; sodium ozagrel for injection, prepared from the ozagrel compound of such crystal form, is high in redissolving performance, and insoluble particles have smaller change after an injection solution is combined; after redissolving, the contents of specific impurities I and II in the solution are obviously less than those in the prior art.

The invention provides sodium ozagrel freeze-dried powder for injection. The sodium ozagrel freeze-dried powder comprises formula components in parts by weight as follows: 60-80 parts of ozagrel, 120-150 parts of mannitol and 10-20 parts of sodium hydroxide. The sodium ozagrel freeze-dried powder has simple formula and fewer auxiliary materials and is applicable to popularization, side effects caused by excessive addition of auxiliary materials are avoided, and the safety of clinical use is improved. The invention further provides a preparation method of the sodium ozagrel freeze-dried powder for injection. Through accurate control on parameters such as the heating speed, the holding temperature, the holding time, the pressure and the like of freeze-drying process steps, the obtained sodium ozagrel freeze-dried powder for injection is more normative in preparation course, good in product quality and high in stability.

The invention researches a new preparation method by aiming at the problems of side effect and inconvenient use of the clinical application of an Ozagrel sodium refrigerated dry powder injection and applies polyglucose to the Ozagrel sodium refrigerated dry powder injection for the first time, the Ozagrel sodium refrigerated dry powder injection is decolorized by active carbon and filtered by a filter film with the aperture of 0.22 micrometer so as to solve the poor appearance problem of the Ozagrel sodium powder injection, achieve the purposes of convenient use, cost reduction, curative effect guarantee and side effect reduction and solve the problem of unqualified clarity generated by applying the polyglucose to the refrigerated dry injection.

The invention discloses injection ozagrel sodium freeze-dried powder for treating cerebral infarction, and belongs to the technical field of medicines. The ozagrel sodium is a crystal, and the novel crystal form of ozagrel sodium, provided by the invention, is different from a crystal structure of the prior art, and experiments prove that the novel crystal form compound is high in purity, good in fluidity and stability and low in impurity content, cannot absorb moisture easily, is safe and reliable in clinical application; and a powder injection prepared by using the novel crystal form compound is good in stability after being compatible with a solvent and extremely low in insoluble micro-particle content, and is very suitable for clinical application.

A composite medicine in the form of injection or orally taken medicine for treating cardiovascular and cerebrovascular diseases, such as coronary heart disease, angina pectoris, apoplexy sequelae, cerebral thrombus, etc, is prepared from Chinese angelica root or its extract and ozagrel. Its preparing process and quality control method are also disclosed.

A composite medicine in the form of injection or orally taken medicine for treating cardiovascular and cerebrovascular diseases, such as coronary heart disease, angina pectoris, apoplexy sequelae, cerebral thrombus, etc, is prepared from acanthopanax bark or its extract and ozagrel. Its preparing process and quality control method are also disclosed.

The invention discloses a preparation process of an ozagrel intermediate methyl (E)-4-(imidazolylmethyl) cinnamate. The preparation process comprises the following steps: (1) preparing imidazolium salt: putting DMF (dimethyl formamide) in a reaction kettle, putting potassium hydroxide and imidazole, stirring the materials to react, then adding potassium carbonate, stirring the materials for hours and removing water generated by a reaction system, thus obtaining a DMF solution of imidazolium salt; (2) preparing methyl (E)-4-(imidazolylmethyl) cinnamate: dissolving methyl p-bromomethyl cinnamate in DMF and dropwise adding the solution to the DMF solution of imidazolium salt; adding deionized water and stirring the materials for crystallization, thus obtaining methyl (E)-4-(imidazolylmethyl) cinnamate. The preparation process has the beneficial effects that the appearance of obtained methyl (E)-4-(imidazolylmethyl) cinnamate is obviously changed and methyl (E)-4-(imidazolylmethyl) cinnamate becomes an off-white solid, thus being beneficial to improving the quality of ozagrel; the production cycle is substantially shortened and the material cost is reduced.

A composite medicine in the form of injection or orally taken medicine for treating cardiovascular and cerebrovascular diseases, such as coronary heart disease, angina pectoris, apoplexy sequelae, cerebral thrombus, etc, is prepared from Chuan-xiong rhizonme or its extract and ozagrel. Its preparing process and quality control method are also disclosed.

The invention relates to a method for preventing and treating thrombogenesis. The method comprises the step of supplying Ozagrel hydrochloride oral preparation to an object needing prevention and treating of thrombogenesis, with 25-800mg and 1-4 times each day.