34 results about "Cilastatin sodium" patented technology

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.

The invention discloses a preparation method of cilastatin sodium, comprising the following steps of: taking 7-chloro-oxo-ethyl oenanthate and (S)-(+)-2, 2-dimethyl cyclopropane formamide as raw materials, and carrying out condensation reaction and basic hydrolysis to obtain (Z)-7-chloro-2((S)-2, 2-dimethyl cyclopropane formamido)-2-heptenoic acid; then, adding alkaline compound for reaction, and separating and purifying to obtain (Z)-7-chloro-2((S)-2, 2-dimethyl cyclopropane formamido)-2-heptenoic acid metal salt crystal; leading the metal salt crystal and cysteine hydrochloride for condensation reaction, acidizing the reaction liquid by hydrochloric acid, washing by organic solvent and concentrating, then loading sample into macroporous absorption resin for purifying, directly using sodium hydroxide solution for elution, and obtaining cilastatin sodium solid after the treatment of eluent. The preparation method simplifies the preparation technique, and effectively improves the chrominance, the purity and the yield of the cilastatin sodium.

The invention relates to a pharmaceutical composition containing imipenem cilastatin sodium and preparation thereof, belongs to the field of medicine and aims at overcoming the technical shortcoming that an imipenem cilastatin sodium powder injection in the prior art causes large adverse effect on the centre. The invention provides a powder injection containing the imipenem cilastatin sodium through reasonable compatibility. The powder injection can effectively reduce the adverse effect on the centre of an imipenem cilastatin sodium compound preparation when being used for clinic antibacterial treatment, the stability of the re-dissolved powder injection can be remarkably improved, and therefore, the pharmaceutical composition is suitable for development of clinic treatment medicine.

The invention dislcloses the process for preparing Imipenem/Cilastatin Sodiun cryodesiccation powder preparation, which is prepared from imipenem, Cilastatin Sodium or the mixture of imipenem and Cilastatin Sodium.

The invention discloses a method for synthesizing cilastatin sodium, comprising the following steps: preparing (Z)-7-iodine-2-((S)-2, 2-dimethyl cyclopropane formamido)-2-heptenoic acid alkyl ester by reaction of (Z)-7-chlorine-2-((S)-2, 2-dimethyl cyclopropane formamido)-2-heptenoic acid alkyl ester and sodium iodide; enabling (Z)-7-iodine-2-((S)-2, 2-dimethyl cyclopropane formamido)-2-heptenoic acid alkyl ester, cysteine alkyl ester hydrochloride, alkali and a solvent to react to obtain cilastatin dialkyl ester; and enabling the cilastatin dialkyl ester and sodium hydroxide to react to obtain cilastatin sodium. The alkali used in the method can be one of or more of K2HPO4, CsCO3 and K3PO4, thereby avoiding the usage of strong alkali and an anhydrous reaction system and realizing mild reaction and easy operation. The method has the advantages of good economical efficiency, mild reaction conditions, high yield, little three wastes (waste gas, waste water and industrial residue) and no pollution and can be used for industrialization production. The product can be separated easily and has high purity.

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 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 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 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 organic chemical synthesis, and provides a method for preparing a cilastatin sodium key intermediate. The method comprises the following steps: by taking 7-halogen-2-oxoethyl heptanoate and (S)-2,2-dimethylcyclopropanecarboxamide as raw materials, carrying out a condensation reaction to obtain a reaction solution of Z/E type 7-halogen-2((S)-2,2-dimethylcyclopropanecarboxamide)-2-ethyl heptenoate, and irradiating the reaction solution under an ultraviolet lamp to obtain the high-purity Z type cilastatin sodium key intermediate. According to the method, thegeneration of impurities is reduced, the efficiency of the isomerization process is improved, the preparation process is simplified, and the yield and the purity of the cilastatin sodium key intermediate are effectively improved.

The invention relates to imipenem and cilastatin sodium for injection and a preparation process of the imipenem and cilastatin sodium for injection, and belongs to the field of medicines. The preparation process of the imipenem and cilastatin sodium for injection comprises the following steps: mixing imipenem, cilastatin sodium and sodium bicarbonate under a sterile condition, and separately packing the mixture in sterile glass bottles in a screw feeding mode. The problem that the imipenem and the cilastatin sodium are uniformly mixed difficultly is solved, meanwhile, drugs in the imipenem andcilastatin sodium for injection are uniform, and layering cannot be caused easily. The imipenem and cilastatin sodium prepared by the preparation process of the imipenem and cilastatin sodium for injection comprises the imipenem, the cilastatin sodium and the sodium bicarbonate according to the mass ratio of 1: 1: (0.01-0.1) successively, the quality of the imipenem and cilastatin sodium for injection is stable, the imipenem and the cilastatin sodium are mixed uniformly, and layering is not caused easily.

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.