38 results about "Cefcapene pivoxil hydrochloride" patented technology

The invention belongs to the technical field of antibiotic drug synthesis, in particular to a synthesis methodof cefcapene pivoxil hydrochloride. The invention is mainly used for process improvement and optimization of cefcapene pivoxil, and the advantage of the synthesis process of cefcapene pivoxil are obvious; new catalytic agents are used, such as phenol, boric acid and other reagents, thereby improving the product quality, increasing the yield, simplifying the operating steps and realizing greater productivity effect and social effect.

The invention discloses a preparation method for cefcapene pivoxil hydrochloride. The method comprises the following steps: (1) stirring and dissolving a compound which is shown as formula (I) in pyridine, adding methylsufonyl chloride to react to obtain a liquid which contains the compound shown as formula (II), placing the liquid at -15 DEG C to 0 DEG C for later use; (2) in the existence of proline and diisopropylamine, enabling 7-HACA and the liquid which contains the compound shown as the formula (II) to react in methyl alcohol to obtain the compound which is shown as formula (III); (3) adding diisopropylamine, enabling the compound which is shown as the formula (III) and chlorosulfonyl isocyanate to react, regulating the pH to 4 to 5, cooling the organic phase, and adding the diisopropylamine to obtain the compound which is shown as formula (IV); (4) in the existence of potassium phosphate and copper acetate, enabling the compound which is shown as the formula (IV) and iodomethyl pivalate to react in DMF (Dimethyl Formamide) to obtain the compound which is shown as formula (V); (5) removing protecting groups from the compound which is shown as the formula (V) in the methanol solution of hydrochloric acid to obtain the cefcapene pivoxil hydrochloride. According to the method, the product yield is greatly improved, and the method is suitable 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 discloses a pharmaceutical composition of cefcapene pivoxil hydrochloride granules, which utilizes high-efficiency antibacterial action of cefcapene pivoxil and adopts oral preparation drug administration, thus having antibiosis function rapidly. The pharmaceutical composition has the expected performance characteristic in the aspect of covering the bitter taste of cefcapene pivoxil hydrochloride, and has high bioavailability and stability of the cefcapene pivoxil hydrochloride, thus being beneficial to orally taking the cefcapene pivoxil hydrochloride. The invention also relates to a preparation method of the pharmaceutical composition of the cefcapene pivoxil hydrochloride granules.

The invention relates to a cefcapene pivoxil hydrochloride and a method for preparing an intermediate of cefcapene pivoxil hydrochloride, the method is characterized in that 7-DACA (iii) is taken as a raw material, and is performed condensation reaction with cefcapene pivoxil hydrochloride side chain acid (iv) and a carbamylated reagent to obtain tertbutyloxycarbonyl cefcapene acid sodium salt (vi), an amino protective group is removed to obtain the cephalospene acid (ii), then performed esterification reaction with iodomethyl pivalate, salifying with hydrochloric acid to obtain the cefcapene pivoxil hydrochloride hydrate (i) (a flow chart is shown as follows). The preparation method has the advantages of cheap raw material, easy raw material acquisition, less reaction step, high yield and high purity of intermediate and product, and is suitable for industrial production.

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 a method for preparing cefcapene pivoxil hydrochloride shown as a formula (I). By the method, the reaction time is shortened, the yield is improved, and the safety is high, so that the method is suitable for industrial production.

The invention relates to a preparation method of cefcapene pivoxil hydrochloride and a synthesis intermediate cefcapene pivoxil sulfonate. According to the invention, a sulfonic acid derivative V is used to perform a de-Boc reaction with cefcapene pivoxil tert-butoxycarbonyl as shown in a formula II to obtain the cefcapene pivoxil sulfonate as shown in a formula IV, and the cefcapene pivoxil sulfonate is then transferred into the cefcapene pivoxil hydrochloride as shown in the formula I. The method provided by the invention is mild in reaction conditions and simple and convenient to operate, meets requirements of environmental protection, and green and safe production; and the prepared cefcapene pivoxil sulfonate is high in purity, can be further transferred into the cefcapene pivoxil hydrochloride, with a purity of more than 99.5 % and high product quality.

The invention discloses a pharmaceutical composition containing cefcapene pivoxil hydrochloride. By adding acesulfame potassium into the pharmaceutical composition to serve as a gelation inhibitor, the phenomenon is effectively inhibited that a solid preparation gelatinizes in an aqueous solution, the dissolving performance of the solid preparation is effectively improved, and therefore the bioavailability is improved. Besides, by utilizing the sweetening property of acesulfame potassium, the bitter taste problem of a granular preparation is solved. Through a dry granulation technology, moisture, high temperature and other adverse factors are avoided, and in combination with a preparation prescription, and the problem is solved that ester bonds, amide bonds, lactam bonds and primary aminegroups in active pharmaceutical ingredient molecules are hydrolyzed or oxidatively degraded. Through experiments, it is proved that the effects of the pharmaceutical composition containing cefcapene pivoxil hydrochloride are good.

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 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 the technical field of medicine, in particular to a cefcapene pivoxil hydrochloride granule and a preparation method thereof. The cefcapene pivoxil hydrochloride granule comprises cefcapene pivoxil hydrochloride, microcrystalline cellulose, mannitol, croscarmellose sodium, hydroxypropyl methylcellulose, talcum powder and steviosin. The obtained cefcapene pivoxil hydrochloride granule is good in stability, rapid in disintegration, good in taste and good in curative effect, and has an obvious anti-inflammatory effect which is remarkably higher than inflammatory effect inthe prior art.

The invention discloses a cefcapene pivoxil hydrochloride composition which is obtained by tabletting cefcapene pivoxil hydrochloride, starch, hydroxy propyl cellulose, carboxymethyl starch sodium, magnesium stearate and medical film coating premixed excipients. The cefcapene pivoxil hydrochloride composition has the benefits that the dissolution of the cefcapene pivoxil hydrochloride composition reaches above 90 percent, the use effect of the cefcapene pivoxil hydrochloride composition is improved, and the utilization rate of drugs can be effectively improved.

The invention relates to the technical field of synthesis of related impurities of medicines, and provides a synthesis method of cefcapene acid. The method comprises the following steps: taking BCN as a raw material, neutralizing diisopropylamine salt in BCN with acid to obtain desalted BCN, then removing a BOC protecting group to obtain a cefcapene acid crude product, then purifying with alkali to remove salt formed by cefcapene acid and inorganic acid and alkali-soluble impurities, and finally cooling and crystallizing under an acidic condition, so that the acid-soluble impurities are left in mother liquor, and the separated crystal is high-purity cefcapene acid. The synthesis method provided by the invention is high in production efficiency, the purity of the obtained product is more than 98%, the high-purity cefcapene acid can be used as a reference substance for analyzing the key impurity in the cefcapene pivoxil hydrochloride, and the method plays a positive role in quality control of the cefcapene pivoxil hydrochloride.

The invention relates to a refining method for cefcapene pivoxil hydrochloride, and belongs to the technical field of pharmaceutical synthesis. A crude cefcapene pivoxil hydrochloride product is dissolved, the pH is regulated, the product is subjected to standing layering, a water layer is abandoned, an organic layer is taken and subjected to reduced pressure distillation, an organic solvent is recovered, then an ester crystallization solvent is added to distillation residues, the temperature is controlled, a hydrochloric acid solution is added for salifying, and a refined cefcapene pivoxil hydrochloride product is obtained after crystal growing, filtering, washing and drying. According to the refining method for cefcapene pivoxil hydrochloride, single ester solvent is used for crystallization, an ester solvent can be recovered from filtered ester mother liquor through reduced pressure distillation and be reused, the production cost is reduced greatly, reaction raw materials are simple and easy to obtain, the process is simple, reaction conditions are mild, and the method is environment-friendly and suitable for large-scale popularization and application.

The present invention discloses to a cefcapene pivoxil hydrochloride tablet preparation method capable of improving tablet quality. The preparation method comprises wet pelletizing, dry granulating and tabletting, wherein the wet pelletizing comprises: mixing and heating partial starch and purified water to prepare a binder solution, carrying out stirring mixing on cefcapene pivoxil hydrochloride, the remaining starch, hydroxypropyl cellulose and sodium carboxymethyl starch for 5-10 min in a pelleter having the stirring function, carrying out pressurization spraying of the binder solution into the pelleter at the stirring state, and carrying out wet mixing on the raw materials through the pelletizing cutter of the pelleter by adopting the self-cutting speed after completing the liquid spraying so as to obtain the wet particles. According to the present invention, the raw material addition, the stirring speed, the stirring time and the pelletizing speed during the preparation process are controlled so as to effectively improve the product quality.