30 results about "Cisatracurium Besylate" patented technology

The present invention provides novel isoquinolinium compounds, methods of producing the isoquinolinium compounds, and methods for converting them into cisatracurium, e.g., cisatracurium besylate. The isoquinolinium compounds of the present invention can be obtained in the form of solids, which can be purified using simple techniques and can be used to afford pure cisatracurium besylate without HPLC purification

The invention discloses a preparation method of cisatracurium besylate. The method comprises the following steps: carrying out weal base dissociation on a R-tetrahydropapaverine-N-acetyl-L-leucine salt having a chiral purity of above 99.5% as a starting material so as to obtain R-tetrahydropapaverine; then carrying out a reaction on R-tetrahydropapaverine and 1,5-pentyl glycol diacrylate so as toobtain (1R,1'R)-2,2'-(3,11-dioxo-4,10-dioxa-1,13-subtridecyl) di[1,2,3,4-tetralin-6,7-dimethoxy-1-(3,4-dimethoxyl)benzyl]isoquinoline; after carrying out oxalate refinement and weal base dissociation, carrying out a reaction on (1R,1'R)-2,2'-(3,11-dioxo-4,10-dioxa-1,13-subtridecyl) di[1,2,3,4-tetralin-6,7-dimethoxy-1-(3,4-dimethoxyl)benzyl]isoquinoline and methyl benzenesulfonate so as to prepare1R,1'R-atracurium besilate; and finally, carrying out column chromatography separation on 1R,1'R-atracurium besilate so as to obtain cisatracurium besylate. By using the preparation method, the yieldof cisatracurium besylate can reach 30%, the purity of the product reaches above 98.6%, and single impurity content is below 0.3; and the process is brief, the yield is stable, and the product quality is good, thus the preparation method disclosed by the invention has an industrial application prospect.

The present invention provides processes for producing isoquinolinium compounds, and for converting them into cisatracurium salts, e.g., cisatracurium besylate

The invention relates to a Cisatracurium besylate lyophilized preparation composition stable at room temperature and a preparation method thereof. The lyophilized preparation contains benzene sulfonic acid Cisatracurium besylate and a lyophilization excipient, a weight ratio of the lyophilization excipient to the benzene sulfonic acid Cisatracurium besylate (W / W) is 1:1-5:1. The lyophilized preparation overcomes the defect of cryopreservation of an existing lyophilized preparation, and is convenient for hospitals and patients for storage. The lyophilized preparation is used for muscle relaxation for operation patients.

The invention relates to the drug synthesis field and particularly relates to a preparation method of high-purity cisatracurium besylate. The preparation method comprises the steps of reacting by virtue of a compound of a formula (III) and benzenesulfonic acid, carrying out substitution reaction on an obtained compound of a formula (IV) so as to generate a compound of a formula (V), and reacting by virtue of the compound of the formula (V) with 1,5-dichloropentane so as to generate cisatracurium besylate. An intermediate and sodium hydroxide or sodium hydrogen carbonate form sodium salt in a preparation process, namely that the intermediate is purified, so that reaction conditions of a laboratory and the production are easily met and controlled, the production efficiency is high, side reaction is little, the product purity is high, and sodium hydroxide or sodium hydrogen carbonate is easily available and relatively low in price.

The invention discloses an industrial purification and preparation method for cisatracurium besylate. According to the preparation method, the refining operation process is simplified, and firstly, under the circumstance of not changing a base, high-purity cisatracurium besylate is obtained in a non-column chromatography preparation mode. By adopting the preparation method disclosed by the invention, the production cycle is shortened greatly, productivity is improved, the yield reaches 40% or above, the content of cisatracurium besylate in a product is not less than 98%, the total content of impurities is less than or equal to 2%, the content of mono-quaternaries is less than or equal to 0.5%, the content of other single maximum impurity is less than or equal to 0.5%, and the content of all isomers is less than or equal to 0.1%.

The invention relates to an industrial preparation method of cisatracurium besylate. The preparation method simplifies the refinement operation process, and obtains the high-purity cisatracurium besylate in a non-chromatographic column chromatography preparation mode under the condition of not changing the salt base for the first time. The preparation method can greatly shorten the production cycle, enhance the productivity and increase the yield to 45% above. In the product, the content of cisatracurium besylate is not lower than 98%, the content of total impurities does not exceed 2%, the content of mono quaternary ammonium salts does not exceed 0.2%, the content of other maximum individual impurities does not exceed 0.3%, and the content of isomers does not exceed 0.1%.

The invention relates to injection cisatracurium besylate for storage and transportation at 25 DEG C and a preparation and freeze-drying production process of the injection cisatracurium besylate. The specific formula of the injection cisatracurium besylate includes 10 mg to 20 mg of cisatracurium besilate, 20 mg to 50 mg of dextran, 50 mg of mannitol and 2000 ml to 3000 ml of water for injection, wherein the PH of a solution containing 20% benzenesulfonic acid is properly adjusted. The freeze-drying production process includes pre-freezing, sublimation drying, re-drying, tamponade and cover rolling. By the adoption of the freeze-drying production process, the chemical stability of the medicine is improved, the cisatracurium besylate can be stored, transported and used at the temperature below 25 DEG C, product quality is guaranteed, storage and transportation conditions of a finished product are reduced, product quality is improved, and the cisatracurium besylate has the important significance in the medical application field.

The invention discloses cisatracurium besylate injection and a preparation method thereof. The cisatracurium besylate injection can be subjected to constant-temptation fluid preparation and storage, also can be applied in a clinical compatibility way, is high in safety, is high in medicine compliance and provides a new choice for clinical application. The injection consists of cisatracurium besylate, citric acid and ethyl alcohol, is safe and stable, and has the advantages of a moderate fluid preparation technology and storage condition and good clinical compliance.

The invention provides a preparation method and application of cisatracurium besylate, and the preparation method comprises the following steps: (1) dissolving R-tetrahydropapaverine-N-acetyl-L-leucine salt, adjusting the pH value with an alkaline solution, and then mixing with methyl 3-bromopropionate and alkali for reaction to obtain an intermediate A; (2) mixing and reacting the intermediate A obtained in the step (1) with alkali to obtain an intermediate B; (3) mixing and reacting the intermediate B obtained in the step (2) with a methylation reagent to obtain an intermediate C; and (4) mixing and reacting the intermediate C obtained in the step (3), a catalyst and a dehydrating agent to obtain cisatracurium besylate. The preparation method provided by the invention is safe in production process, high in yield, few in isomer and low in maximum single impurity.

The invention relates to a preparation method of a cisatracurium besylate impurity O. The preparation method comprises the following steps: S1, taking (1R)-1-[(3, 4-dimethoxyphenyl)-methyl]-1, 2, 3, 4-tetrahydro-6, 7-dimethoxy-2-methoxycarbonyl ethyl-isoquinoline, methyl benzenesulfonate, acetonitrile and a catalyst to react, so as to obtain a cisatracurium besylate impurity D; s2, taking the impurity D, 1, 5-pentanediol, dichloromethane and a catalyst to react to obtain an impurity F; s3, taking the impurity F, acryloyl chloride, dichloromethane and a catalyst to react to obtain an impurity O crude product; and S4, preparing a purified impurity O pure product through a liquid phase. According to the method, the defect that an effective method for preparing the cisatracurium besylate impurity O is lacked in the prior art is overcome, the purity of the prepared impurity O is high, the preparation method is simple, the used reagent is low in price and easy to obtain, the yield is high, and the impurities D and F can be prepared in the synthesis route.