50 results about "CEFMINOX SODIUM" patented technology

The invention provides a cefminox sodium compound of a new route, in particular a method for producing the cefminox sodium compound. The method comprises a step of generating cefminox sodium through the reaction between 7beta-bromoacetamido-7a-methoxyl-3-(1-methyl-1H-tetrazole-5-S-methyl)-3-cephem-4-carboxylic acid and D-cysteine hydrochloride, and is characterized in that: the reaction condition of the step is that the reaction is performed in aqueous solution, sodium iodide is used as a catalyst, the pH value of the reaction system is between 7.5 and 8.0, and the reaction temperature is kept at 30+/-5 DEG C. Compared with the method for producing the cefminox sodium compound in the prior art, the method of the invention for producing the cefminox sodium compound greatly improves the product yield and the purity, and solves the problem that a cefminox sodium bulk drug always has a low purity in the prior art.

The invention relates to a cefminox sodium crystalline compound. The cefminox sodium crystalline compound is determined by a powder X-ray diffraction determination method; and characteristic diffraction peaks are displayed at 5.1, 6.9, 8.5, 10.3, 12.1, 15.1, 15.9, 17.4, 19.5, 21.7 and 24.6 degrees in an X-ray powder diffraction pattern represented by a diffraction angle of 2 theta+/-0.2 degree. The invention also relates to cefminox sodium composition powder injection containing the cefminox sodium crystalline compound. The composition powder injection comprises the following components: 95 to 100 parts of cefminox sodium crystalline compound and 0.1 to 1 part of sodium benzoate.

The invention discloses a preparation method of cefminox sodium, which comprises the following steps: 7 beta-bromoacetamide-7 alpha-methoxy-3-(1-methyl-1H-5-tetrazyl)sulfur methyl-3- cephem-4-carboxylic acid and D-cysteine hydrochloride are dissolved in water, the pH value is regulated to 6.0-7.0 by sodium bicarbonate, condensation reaction is carried out, and reaction products are post-treated to obtain the cefminox sodium. In the method, cefminox sodium raw material can be prepared through low-temperature reaction, a nonpolar macroporous resin X5 chromatography column is used for purification, ethanol-aqueous solution or anhydrous alcohol recrystallization and other simple operations are adopted to obtain target products, the yield and the purity of the target products are high, the products have uniform crystal forms and good fluidity, no special equipment is needed for the production, and the method is suitable for industrial production.

The present invention relates to a kind of preparation of medicinal compound, particularly a kind of preparation method of cefminox sodium. The present invention adopts a synthesis route using 7-ACA as a starting material, and the cost of raw materials is lower than that of a synthesis route using 7-MAC as a starting material. The new synthetic route uses dichloroacetyl chloride instead of bromoacetyl bromide, which reduces the toxicity and cost of raw materials. The new synthetic route increases the intermediate treatment process, reduces the amount of impurities brought by the intermediate into the next reaction, and improves the quality and stability of the finished product. The present invention overcomes the shortcomings of the synthetic route using 7-MAC as the starting material through the above improvements.

The invention provides a cefminox sodium liposome preparation which is a powder injection. Cefminox sodium is wrapped in liposome in the form of the liposome, and the cefminox sodium liposome preparation comprises the following components by weight part: 0.1-5 parts of cefminox sodium, 1-50 parts of soya bean lecithin, 0.1-40 parts of cholesterol, 0.1-20 parts of antioxidant and 1-60 parts of proppant. The cefminox sodium liposome preparation has good preparation stability and cannot crack because of dewatering, fusion, ice crystal generation, and the like in a freeze-drying process; and after hydrated re-dissolution, the cefminox sodium liposome preparation still can maintain good entrapment rate.

The invention discloses a method to separate and purify cefminox sodium. Solvent is prepared from trichloromethane, ethyl acetate, carbinol and water, with the upper phase being stationary and the lower phase being mobile. The whole column of a high-speed countercurrent chromatograph is filled with stationary phase solvent and then the mobile phase solvent is pumped into the column; the raw material of cefminox sodium is dissolved in the solvent at the lower phase and the material is fed by an injection valve; above 98% of the product is collected according to the map of the detector and then the solvent is removed to obtain refined cefminox sodium. The method is good in effect and the product is of high purity. The cefminox sodium can be further froze and dried to prepare freeze-dried powder injection. The method is good in separation effect and the product is of high purity.

The invention relates to a cephamycin intermediate compound and a preparation method thereof. The cephamycin intermediate compound has a structure of formula (I), and is prepared by directly reacting 7beta-chloroacetamide-7alpha-methoxy-3-(1-methyl-1H-tetrazole-5-thiomethyl)-3-cephem-4-carboxylic acid and dicyclohexylamine in a specific solvent to form a salt and crystallizing. The cephamycin intermediate compound has the characteristics of high purity, high stability and the like, is conductive to improving the purity of cephamycin final products such as cefminox sodium, cefmetazole sodium and cefotetan disodium, and is beneficial to large-scale production and application.

The invention aims at providing a cefminox sodium compound and a new preparation method thereof. The refinement and the purification of the cefminox sodium compound can be achieved by acid-base reaction, activated carbon adsorption, electrodialyzer treatment and adsorption, separation and purification of a chromatographic column. The purity of final products is higher than that of the traditional product, the quality of preparation products is improved, the toxic and side effects are reduced, and the safety of clinical medicaments is ensured.

The invention discloses a synthesis method for cefminox sodium. The method comprises the following steps: by taking cefminox mother nucleus 7-AMCA as a raw material, carrying out acylation reaction and decarboxylate protection reaction to obtain a mixed liquor; processing and condensing the mixed liquid into cefminox acid, and salifying without separation of an intermediate to synthesize cefminox sodium in one step. In the manner, by adopting the synthesis method for cefminox sodium disclosed by the invention, a plurality of reaction steps can be finished one time without separation, a sterile cefminox sodium product can be obtained by a continuous operation one time, the total yield can be up to 90% by taking 7-AMCA as an initial raw material, the process route is short, and the adopted reaction agent is low in price and low in cost.

The invention belongs to the technical field of medicine, and particularly relates to a cefminox sodium crystal form compound. The structure formula of the cefminox sodium crystal form compound is shown as follows. The X-ray powder diffraction spectrum obtained by using Cu-K[alpha] ray of the cefminox sodium crystal form compound is shown as the figure 1. The cefminox sodium crystal form compound is a novel crystal form compound different from compounds in the prior art, and has better dissolution rate. Insoluble particles precipitated after the cefminox sodium crystal form compound is put for a long time are less than that of the compounds in the prior art. A cefminox sodium aseptic powder injection prepared from the cefminox sodium crystal form compound has good clinical effects for respiratory tract bacterial infection and bacteria curative effects, and has low occurrence rate of untoward effects.

The invention belongs to the technical field of medicines, and in particular relates to a cefminox sodium compound. The structural formula of the cefminox sodium compound is shown in the specification and an X-ray powder diffraction spectrum of the cefminox sodium compound, which is measured through Cu-K(alpha) ray, is shown in Figure 1. Furthermore, the invention provides a preparation method of the cefminox sodium compound, a pharmaceutical composition containing the cefminox sodium compound, and a preparation method of the pharmaceutical composition. The dosage form of cefminox sodium medicine is sterile powder injection. The cefminox sodium compound and the pharmaceutical composition thereof provided by the invention, in comparison with the prior art, have better storage stability and liquidity and are easier to sub-package and mix; and the cefminox sodium compound and the pharmaceutical composition thereof greatly enhance the medication safety of patients.

The invention aims at providing a synthesis method of cefminox sodium. The synthesis method specifically comprises the following steps: firstly, mixing 7beta-amino-7alpha-methoxy-3-[(1-methyl-1H-5-tetrazolyl)-mercapto methyl]-3-cephem-4-methyl diphenyl carboxylate and dichloromethane (7-MAC), and bromoacetamide bromine under a certain condition to obtain 7beta-bromoacetyl amino-7alpha-methoxy-3-[(1-methyl-1H-5-tetrazolyl)-mercapto methyl]-3-cephem-4-methyl diphenyl carboxylate; then removing a carboxylic acid protection group to obtain 7beta-bromoacetyl amino-7alpha-methoxy-3-[(1-methyl-1H-5-tetrazolyl)-mercapto methyl]-3-cephem-4-carboxylic acid; then enabling the 7beta-bromoacetyl amino-7alpha-methoxy-3-[(1-methyl-1H-5-tetrazolyl)-mercapto methyl]-3-cephem-4-carboxylic acid to react withD-cysteine hydrochloride to obtain the cefminox sodium. According to the synthesis method provided by the invention, the product yield and purity of the synthesized cefminox sodium are high; phosphoric acid loaded activated carbon is used as a solid catalyst and is easy to separate from a reaction system, and the formation of acid waste liquid is avoided.

The invention relates to a preparation method for a cephamycin intermediate. A compound of the cephamycin intermediate can be seen in the formula (IV). The cephamycin intermediate is obtained by making 7-ACA react with dichloroacetyl chloride in specific solvent, making the obtained product react with MMT under catalysis of a sulfoacid catalyst and conducting crystallization. The cephamycin intermediate has the advantages of being high in purity and stability and the like, is beneficial for improving the purity of final cephamycin products such as cefminox sodium, cefmetazole and cefotetan disodium, and is beneficial to large-scale production and application.

The invention discloses a preparation method of an intermediate D-cysteine hydrochloride monohydrate which is used for synthetizing third generation cephalosporin antibiotic cefminox sodium. The preparation method comprises the following steps: taking L-cysteine, acetone and L-tartaric acid as raw materials which are subjected to a reaction with acetone and acetate (or propionic acid) mediums, utilizing an asymmetric transforming agent salicylic aldehyde to carry out asymmetric transformation to form D-2,2-dimethyl thiazolidine-4-carboxylic acid-L-tartrate; carrying out hydrolyzation, crystallization, filteration and drying treatments on double salt to obtain D-cysteine; generating hydrochloride after a reaction between the D-cysteine and hydrochloric acid with a content of 16-31%, and carrying out dissolving, decolouring, distillation and recrystallization treatments to obtain the D-cysteine hydrochloride-hydrate product. The preparation method in the invention has the advantages of simple process, high product yield, high chemical purity and high optical purity. Recycle and reuse of input solvent and unreacted raw material facilitate industrialization production.

The invention discloses a cefminox sodium preparation. The cefminox sodium preparation is prepared from the raw materials: cefminox sodium used as medicine, N-(beta-D-glucopyranose) octanamide and a film-forming lipid material; and the cefminox sodium preparation is further prepared from the raw materials: tartaric acid and solid sodium bicarbonate particles. In addition, the invention further discloses a preparation method and a use method of precursor liposomes. A precursor liposome pharmaceutical preparation is prepared by using solid dispersion, liposome suspension liquid is prepared by combining with an effervescence technology, the stability of the long-term storage of the precursor liposomes can be achieved, morphological consistency of the liposomes can further be maintained better, the particle size distribution is narrow, and the entrapment efficiency is not significantly reduced.

The invention discloses a preparation method of a cefminox sodium powder-needle preparation for injection, and belongs to the technical field of biomedical synthesis. The method comprises: mixing the prepared raw materials, respectively carrying out an acylation reaction and a carboxyl protection removing reaction, treating the solution obtained after the reaction to obtain cefminox, adding sodium carbonate, and crystallizing to obtain cefminox sodium. According to the present invention, the steps are simple, the ladder temperature control mode is used in the reaction temperature control, the complete reaction is ensured through the material feeding time limiting while the production efficiency is improved, the quality of the prepared product is good, and the raw material utilization rate is high.

The invention belongs to the field of biomedical technology, and particularly relates to a cefminox sodium raw material as well as a preparation method and preparation thereof. After many years of creative experiments, applicants obtain the novel cefminox sodium crystal form provided by the invention, the crystal form drug and auxiliary material sodium citrate are combined to prepare the novel powder injection, after the powder injection and a sodium chloride injection or a glucose injection are mixed, the long-term stability is maintained, and insoluble microparticles and the like are hardlyincreased, so that the results further show that the preparation provided by the invention has better stability.

The invention discloses a synthesis method of cefminox sodium, which comprises the following steps: completely dissolving methoxycephalosporin (7-MAC) and dichloromethane in a reaction flask (1), and adding pyridine and carbon tetrachloride; after complete reaction, adding a saturated aqueous solution of sodium chloride for extracting and layering, and performing vacuum concentration on a bottom-phase organic phase; adding dichloromethane and ethanol into a reaction flask (2), and introducing hydrogen chloride gas; after complete reaction, adding the concentrated liquid in the reaction flask (1) into the reaction flask (2); after complete reaction, adding a mixed solvent for extracting and layering; performing liquid separation on the organic phase by use of the saturated aqueous solution of sodium chloride, and keeping the bottom-phase organic phase; adding D-cysteine into the organic phase, adjusting the pH value of the solution to 6.0-6.5, and keeping the temperature at 20-25 DEG C; after sufficient reaction, feeding ethanol, and performing sufficient crystal precipitation and vacuum drying to obtain cefminox sodium. According to the method, the reaction process causes low toxicity, the operation is safe, the quality and yield of the product are increased, and the crystal form of the product is good and easy to dry, thus the method is suitable for popularization and application in mass production.

The invention provides a cefminox sodium drug composition and a preparation method thereof, relating to the fields of pharmaceutical preparations and preparation methods and mainly solving the problems that single preparations of cefminox sodium and metronidazole in the prior art have great dosages, poor treatment effects after being combined and big side effects. The drug composition comprises cefminox sodium and metronidazole lipid microspheres in a weight ratio of (100:3)-(100:10), wherein the weight of the metronidazole lipid microspheres is based on metronidazole. The drug composition is prepared into powder injection. The pH value of water solution of the drug composition is 6.5-7.0. The powder injection of the drug composition provided by the invention not only has high curative effect but also can reduce the dosage of metronidazole by over 80%, thus greatly reducing or avoiding the toxic and side effects, especially gastrointestinal reactions including nausea, emesis, anorexia, abdominal cramp and neurotoxicity, of metronidazole and further reducing the occurrence rate of adverse reactions.

The invention provides a cefminox sodium preparation method, which comprises: (1) dispersing a compound having a structure represented by a formula (VII) in an organic solvent A to prepare a solutionor a suspension, adding a compound having a structure represented by a formula (VII), and carrying out vacuum drying to obtain a compound having a structure represented by a formula (VI); (2) dispersing the compound with the structure represented by the formula (VI) into an organic solvent C, adding a compound having a structure represented by a formula (V) in a dropwise manner, and drying to obtain a compound having a structure represented by a formula (IV); (3) dispersing the compound having the structure represented by the formula (IV) in an organic solvent, and removing the solvent by rotary evaporation under a pressure reducing condition to obtain an organic phase containing a compound having a structure represented by a formula (II); and (4) adding purified water into the solution containing the compound having the structure represented by the formula (II), heating, adjusting the pH value, adding a compound having a structure represented by a formula (III), carrying out temperature control stirring, transferring the water phase into a crystallizing tank, crystallizing, and carrying out pressure reducing drying to obtain the cefminox sodium heptahydrate. According to the invention, the synthesis process is shortened, the cost is reduced, and the product yield and the purity are high.