34 results about "Cilastatin sodium" patented technology

The invention discloses an application of norharmane in improvement of antibiotic antibacterial activity. When norharmane is combined with antibiotic polymyxin B, imipenem-cilastatin sodium or levofloxacin for application, the antibacterial activity on drug-resistant pseudomonas aeruginosa can be enhanced, and a synergistic antibacterial effect can be generated. According to the method for obviously improving the killing capacity of the antibiotics on the drug-resistant pseudomonas aeruginosa, the dosage of the antibiotics required for achieving the same treatment effect is greatly reduced, and a research direction is provided for the development of new drugs and the new use of old drugs.

The invention discloses an Omeprazole sodium pharmaceutical composition containing Omeprazole sodium, Imipenem and Cilastatin sodium. According to the composition, the treatment effect of Omeprazole can be improved, and Omeprazole sodium is unusually stable in the absence of antioxidants and metal chelating agents.

The invention belongs to the field of organic chemical synthesis and provides a method for preparing a key intermediate of cilastatin sodium, the method comprising: using 7-halo-2-ethyl oxoheptanoate and (S)-2, 2- Dimethylcyclopropanecarboxamide is a raw material, and through condensation reaction, Z / E type 7-halogen-2((S)-2,2-dimethylcyclopropanecarboxamide group)-2-heptenoic acid ethyl ester is obtained The reaction solution is placed under an ultraviolet lamp to irradiate to obtain a high-purity Z-type cilastatin sodium key intermediate. The invention reduces the generation of impurities, improves the efficiency of the isomerization process, simplifies the preparation process, and effectively improves the yield and purity of the key intermediate of cilastatin sodium.

The invention provides a preparation method of imipenem-cilastatin sodium sterile powder. With the adoption of the preparation method provided by the present invention, the problem of difficulty in uniform mixing due to big grain diameter difference between imipenem and cilastatin sodium as well as the problem of proneness to oxidation due to sulfur contained in the components in existing preparation technology are solved through the measures of solvent adjusting, spray drying, nitrogen filling, etc.

The invention provides a preparation method of a cilastatin sodium active pharmaceutical ingredient. The preparation method comprises the following steps: (1) mixing alkali and reaction solvent, adding a compound (Z)-7-chloro-2-((S)-2,2-dimethylcyclopropylformacyl)-2-heptenoic acid shown in Formula (V), then adding cysteine hydrochloride, reacting to obtain a reaction solution containing a compound cilastatin shown in Formula (VI); (2) purifying the reaction solution obtained in the step (1) through macroporous adsorption resin to obtain the compound cilastatin shown in Formula (VI); and (3) mixing sodium hydroxide and water, adding the cilastatin obtained in the step (2), regulating the pH value, and drying to obtain the compound cilastatin sodium shown in Formula (I). The preparation method is quick, efficient and suitable for industrial production; and the obtained cilastatin sodium active pharmaceutical ingredient is low in impurity content.

The invention provides an imipenem and cilastatin sodium sterile powder preparation for injection and a preparation method thereof. The solubilizing effect of a pH regulator of sodium bicarbonate on imipenem is utilized; the solubility of the imipenem in a water solution is increased; antioxidants are added, so that the oxidative deterioration of the imipenem and the cilastatin sodium sterile powder preparation in production and storage processes is reduced; the use of medical auxiliary materials is reduced; the manufacturing process is simplified; the cost is reduced; meanwhile, the contents of relevant substances are reduced; the production of the stable-quality imipenem and cilastatin sodium sterile powder preparation for injection can be ensured.

The invention belongs to the technical field of medicines, and particularly provides a cilastatin sodium intermediate preparation method, which comprises: simply preparing a (Z)-7-X-2((2s)-2,2-dimethylcyclopropaneformamido)-2-heptenoic acid crude product through a one-pot method by using 7-X-2-oxoheptanoic acid ethyl ester and (s)-2,2-dimethylcyclopropaneformamide as raw materials sequentially under the action of a catalyst, concentrated hydrochloric acid and hydrogen chloride gas, and re-crystallizing to prepare a (Z)-7-X-2((2s)-2,2-dimethylcyclopropaneformamido)-2-heptenoic acid refined product. According to the invention, the method has advantages of short synthetic route, simple operation and high product purity, and is suitableness for industrial production.

The invention belongs to the field of drug synthesis, and particularly discloses a method for purifying an intermediate of cilastatin sodium. The method includes adding (E-Z)-7-halo-2 ((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid ethyl ester into acetone, stirring, and adding a certain amount of organic alcohol; then dropping purified water, adjusting pH to 4-6 with acid after dropping, cooling to 0-10 DEG C, keeping the temperature and stirring for 3-4 hours; and filtering to obtain a solid, namely Z-7-halo-2 ((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid ethyl ester.Through the technical scheme, the HPLC purity of the product Z-7-halo-2 ((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid ethyl ester reaches more than 99.0%, and the impurity of the E configuration is reduced to less than 0.1%.

The invention belongs to the field of pharmaceutical synthesis, and provides a preparation method of cilastatin sodium, and the method comprises the following steps: performing condensation, alkaline hydrolysis, and thioetherification of raw materials of 7-oxyhalogen alkyl heptylate and (s)-2,2-dimethylcyclopropane methanamide, adjusting the pH value of the thioetherified solution, washing by a nonpolar solvent, performing isomerization, purification by a neutral macroporous adsorption resin, and salt formation so as to obtain the cilastatin sodium solid. The invention reduces the generation of impurities, improves the isomerization efficiency, simplifies the preparation process, and effectively improves the yield and purity of cilastatin sodium.

The invention provides an imipenem and cilastatin sodium pharmaceutical composition liposome injection, comprising imipenem, cilastatin sodium, sphingomyelin, cholesterol, an emulsifier and a cryoprotectant. The imipenem and cilastatin sodium injection prepared by using the method provided by the invention improves the quality of the preparation product, reduces toxic and adverse effects, increases bioavailability of medicinal components, and has good preparation stability. During the lyopilization process, liposomes do not break due to dehydration, fusion, ice crystals, and so on, and after hydration redissolution, liposomes also remain good encapsulation rate.

The invention relates to a method for preparing a compound called cilastatin sodium shown as a formula (I). Cilastatin is prepared by crystallizing and purifying (Z)-7-chlorine-2((S)-2, 2-dimethyl c-pr carbamoyl)-2-heptenoic acid and the cilastatin sodium is prepared by purifying the cilastatin through microporous resin, thereby improving the purity quotient and the yield coefficient of the cilastatin sodium.