32 results about "Cefcapene" patented technology

The invention discloses a synthetic method of cefcapene pivoxil hydrochloride. The synthetic method comprises following steps: 7-aminocephalosporanic acid (7-ACA) is taken as a raw material, and is subjected to 'one-pot reaction' so as to realize 3-esterolysis, and 7-amino protection is carried out; an obtained product is subjected to 'one-pot reaction' so as to realize 3-amidation, and 7-deprotection is carried so as to obtain an important intermediate of cefcapene pivoxil; the intermediate and a derivative of cefcapene pivoxil with an acid side chain are subjected to condensation, and an obtained cefcapene pivoxil precursor with a 4-acid group is subjected to esterification and acidification so as to obtain cefcapene pivoxil hydrochloride finished products. According to the synthetic method, 'atom economy' principle is fully used so as to shorten reaction route, and increase reaction total yield; and it is beneficial for synthetic technology improvement and optimization of cefcapene pivoxil hydrochloride.

The invention relates to a preparation method of cefcapene diisopropylamine salt. The preparation method comprises the following steps: (1) obtaining acylate 3 by using cefcapene side chain acid 2 in the presence of an acylation reagent namely SOCl2 and an acid-binding agent namely triethylamine; (2) obtaining a condensation product 5 by using acylate 3 and a 7-HACA raw material 4 in the presence of triethylamine and a catalyst namely 4-dimethylaminopyridine; (3) enabling the condensation product 5 to react with chlorosulfonic acid isocyanate to obtain a 3-bit aminoacyl ester compound 6; (4) performing salt formation on the compound 6 and diisopropylamine to obtain cefcapene diisopropylamine salt 1. According to the preparation method disclosed by the invention, thionyl chloride is used as the acylation reagent, and triethylamine is used as the acid-binding agent so as to reduce the cost; 4-dimethylaminopyridine with the catalyst amount is added in the step (2) to ensure that the reaction is performed more completely and the reaction time is shortened; the preparation method is simple and convenient in whole route operation, and is convenient for large-scale production.

The invention relates to a crystallization method of cefcapene ester hydrochloride monohydrate, which belongs to the field of medicine. The method comprises the following steps: adding solvents into cefcapene ester hydrochloride for dissolution; adding active carbon for decolourization; carrying out filtration and washing; adding hydrochloric acid water solution into obtained filter liquid for carrying out crystallization; filtering crystals; respectively washing the crystals by water and ethyl acetate; and carrying out drying to obtain the cefcapene ester hydrochloride monohydrate. The method of the invention can use a single solvent of methanol for crystallization to improve the recovery yield and reduce the production cost, and can also use mixed solvents of the methanol and ketone for crystallization to improve the quality of finished product. Low-temperature active carbon is used for decolourization, and the impurity control in the operation process can be ensured at the same time of ensuring the product quality (the control on the color grade, the endotoxin and the like). The baking temperature is reduced, the baking time is shortened, and the quality such as the color grade, the impurity content and the like of the products can be reached. The invention has the advantages of simplicity, easy implementation, low cost, good crystallization clarity, good color grade and easy control on the impurities of the finished products, is suitable for large-scale popularized application, and has obvious economic benefits.

The invention relates to a cefcapene pivoxil hydrochloride composition and a preparation method thereof. The composition consists of a tablet core and a coating layer, wherein the tablet core contains cefcapene pivoxil hydrochloride, a filler, a disintegrating agent, an antisticking agent and a lubricating agent; the grain diameter of the cefcapene pivoxil hydrochloride serving as a raw material is less than 100 micrometers; and the antisticking agent is in an amount which is 3 to 15 percent of the weight of the tablet core. The prepared cefcapene pivoxil hydrochloride tablets have excellent disintegrative property and dissolution of over 75 percent.

The invention relates to a preparation method of a cefcapene lactone compound or a hydrochloride thereof, and belongs to the technical field of synthesis of drug-related impurities. In order to solvethe problems of few synthesis routes and low yield in the prior art, the invention provides a preparation method of a cefcapene lactone compound or a hydrochloride thereof. The method comprises the following steps: carrying out a condensation reaction on (Z)-2-(2-tert-butyloxycarbonylaminothiazole-4-yl)-2-pentenoic acid and hydroxymethyl-7-aminocephalosporanic acid in an organic solvent in the presence of an organic alkali I, continuously adding an organic alkali II to adjust the pH value to 9.0-9.5 after the reaction is finished, and performing lactonization to obtain a compound represented by a formula IV; performing a deprotection reaction on the compound represented by the formula IV in a non-water-soluble organic solvent under the action of a Lewis acid to obtain a compound represented by a formula I; and carrying out a reaction on the compound represented by the formula I and hydrochloric acid to obtain a cefcapene lactone compound hydrochloride when the cefcapene lactone compound hydrochloride is synthesized. The synthetic route is easy to operate, and the yield and the purity are high.

The invention relates to a cefcapene pivoxil hydrochloride composition and a preparation method thereof. The composition comprises a tablet core and a coating layer, wherein the tablet core comprises cefcapene pivoxil hydrochloride, a filler, a disintegrating agent, an antisticking agent and a lubricating agent; the particle size of the raw material of cefcapene pivoxil hydrochloride is smaller than 100 microns; the antisticking agent accounts for 2%-10% in percentage by weight of the tablet core; the filter comprises a filler such as starch and the like and soluble auxiliary materials; and the soluble auxiliary materials accounts for 1%-10% in percentage by weight of the tablet core. The prepared cefcapene pivoxil hydrochloride tablet has good disintegration, and the dissolution of the cefcapene pivoxil hydrochloride tablet reaches over 75%.

The invention relates to a cefcapene pivoxil hydrochloride composition and a preparation method thereof. The composition consists of a tablet core and a coating layer, wherein the tablet core contains cefcapene pivoxil hydrochloride, a filler, a disintegrating agent and a lubricating agent; the grain diameter of the cefcapene pivoxil hydrochloride serving as a raw material is less than 100 micrometers; and the filler consists of a starch filler and soluble auxiliary materials, and the soluble auxiliary materials are in an amount which is 3 to 15 percent of the weight of the tablet core. The prepared cefcapene pivoxil hydrochloride tablets have excellent disintegrative property and dissolution of over 75 percent.

The invention relates to the technical field of medicines, in particular to cefcapene pivoxil hydrochloride hydrate composition tablets. The cefcapene pivoxil hydrochloride hydrate composition tablets comprise the following components in part by weight: 100 parts of cefcapene pivoxil hydrochloride hydrate, 30 parts of microcrystalline cellulose, 22 parts of mannitol, 22 parts of hydroxyl cellulose, 1.5 parts of magnesium stearate and 0.5 to 1 part of lactose. Compared with a positive medicinal control group, the cefcapene pivoxil hydrochloride hydrate composition tablets have the advantage that a medicinal effect is improved obviously.

The invention relates to the technical field of medicine, in particular to a granule of cefcapene pivoxil hydrochloride and a preparation method thereof. The composition comprises cefcapene pivoxil hydrochloride, microcrystalline cellulose, mannitol, and croscarmellose sodium , hypromellose, talc, stevia. The obtained cefcarpine pivoxil hydrochloride has good stability, rapid disintegration, good taste, good curative effect, and obvious anti-inflammatory effect, and the anti-inflammatory effect is significantly higher than that of the prior art.

The invention discloses a one-step preparation method of antibiotic drug cefcapene pivoxil hydrochloride monohydrate, comprising the following steps: adding hydrochloric acid and trifluoroacetic acid into an organic solvent, stirring and cooling down to 0 to -10°C, adding Boc The base-protected cefcapene pivoxil is continued to keep warm and stirred, and the reaction is completed, crystallized and filtered, and dried to obtain cefcapene pivoxil hydrochloride monohydrate; the molar ratio of hydrochloric acid and trifluoroacetic acid is 10:1 to 5:1. The preparation method of cefcapene axetil hydrochloride provided by the invention has high yield, low cost, convenient treatment, good stability, mild reaction conditions, environmental protection, and is suitable for industrialized production.

The invention provides a preparation method of cefcapene pivoxil hydrochloride intermediate BCN, and belongs to the technical field of organic synthesis. Mixed anhydride BAPA prepared by a mixed anhydride preparation reaction and D-7-ACA-MG salt can be subjected to a condensation reaction, and the cefcapene pivoxil hydrochloride intermediate BCN is obtained by carbamoylation reaction and salt formation crystallization. The preparation method has short process route, high product purity and low cost, and is suitable for industrial production. Data of the embodiment shows that the prepared cefcapene pivoxil hydrochloride intermediate BCN can have purity as high as 98.84% and yield as high as 91.99%.

The invention relates to a method for preparing beta-lactam derivative through enzymatic reaction. The method for preparing beat-lactam derivative through enzymatic reaction comprises the step of synthesizing a compound shown in a formula I by virtue of an enzymatic reaction, and the compound can be used for preparing antibacterial cefcapene pivoxil, wherein R is the conventional amino protection groups like a t-butyloxycarboryl group. A biological enzyme catalyst used in the enzymatic reaction is immobilized deacetyl esterase, and the method for synthesizing the compound shown in the formula I has the advantages of mild conditions, low cost and environmental friendliness, and is easy to operate.

A process for producing cefcapene pivoxil methanesulfonate and, with the use thereof as an intermediate, corresponding hydrochloride. There is provided methanesulfonate of the compound of the formula ().

The invention discloses a cefcapene pivoxil hydrochloride synthesis method, and belongs to the technical field of synthesis of cephalosporin medicines. The cefcapene pivoxil hydrochloride synthesis method comprises the following steps: (1) using BCN as a starting material, reacting with an inorganic acid aqueous solution in a solvent to obtain a dissolved clarified solution, standing, layering, abandoning a water layer, collecting an organic layer comprising a compound I, and drying; (2) adding a formic acid and a concentrated hydrochloric acid, reacting at the temperature of 0-5 DEG C, washing with water after finishing reacting, layering, and collecting an organic layer comprising a compound II; (3) adding a sodium bicarbonate aqueous solution and iodomethyl pivalate, maintaining the pHvalue to 5-6, layering after finishing reacting, collecting the organic layer, adding ethanol, washing with water, layering, additionally adding the ethanol in the organic layer, regulating the pH value to 7-8 by using an inorganic base, layering, and collecting an organic layer comprising a compound III; and (4) conducting vacuum concentration until no liquid drop is distilled, adding a solvent,adding a diluted hydrochloric acid, regulating the crystallization, cooling, growing the crystal, conducting suction filtration, and drying to obtain cefcapene pivoxil hydrochloride. The process of the method is simple, the reaction condition is mild, the method is environmentally friendly, the yield is high, the purity is high, and the method is easy for industrial production.

The invention belongs to the technical field of antibiotic synthesis, and relates to a preparation method for cefcapene pivoxil hydrochloride. The preparation method comprises the following steps: (1) reacting 7-ACA with sodium hydroxide in a solution with quaternary ammonium salt under the temperature of (-5 DEG C)-5 DEG C to generate 7-DACA; (2) adding (cefcapene pivoxil side chain acid, compound 5) into the solution containing 7-DACA, diisopropylamine and phenyltriethylammonium chloride under the temperature of 0-10 DEG C to react with a methylsufonyl chloride reaction solution under the temperature of (-15 DEG C)-0 DEG C to obtain a compound (4); reacting the compound 4 and chlorosulfonyl isocyanate to obtain a compound (3); further reacting the compound (3) with iodomethyl pivalate to obtain a compound (2); removing the protection base of the compound (2) in a hydrochloric acid methanol solution to obtain the cefcapene pivoxil hydrochloride (compound 1).

The invention belongs to the technical field of antibiotic drug synthesis, and relates to a method for synthesizing cefcapene pivoxil hydrochloride by an enzymic method, the method comprises the following steps: treating a compound shown in a formula (IV) with acid and alkali in sequence to obtain a compound shown in a formula (III), performing enzymolysis on the compound shown in the formula (III) to obtain a compound shown in a formula (II), the enzyme used for enzymolysis being IPA-750 enzyme; and (2) in the presence of an acid-binding agent, carrying out esterification reaction on the compound as shown in the formula (II) and iodomethyl pivalate, and salifying with hydrochloric acid to obtain the compound cefcapene pivoxil hydrochloride as shown in the formula (I). The invention also provides a synthetic intermediate for synthesizing cefcapene pivoxil hydrochloride by an enzymic method. According to the method for synthesizing the cefcapene pivoxil hydrochloride through the enzyme method and the synthetic intermediate of the cefcapene pivoxil hydrochloride, the reaction conditions are milder, and the obtained product is higher in purity and more environmentally friendly.