30 results about "Cisatracurium Besylate" patented technology

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

The present invention provides R,R′-atracurium salts, processes for producing and purifying such salts, and methods of using such salts to produce highly pure cisatracurium besylate.

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 method for preparing impurity W in cisatracurium besylate, belonging to the technical field of chemical substance synthesis, including A. Take 1,5-pentanediol, glacial acetic acid, and a catalyst to react to obtain a reaction solution; B. Add water and n-hexane to the reaction solution, stir and separate the liquid, and collect the aqueous layer solution; C. Washing the aqueous layer solution with n-hexane, collecting the washed aqueous layer solution; D. Extract the aqueous layer solution with dichloromethane, and collect the dichloromethane layer solution; E. Add a desiccant to the dichloromethane layer solution, filter, and concentrate to obtain 1,5-pentanediol acetate monoester; F. 1,5-pentanediol acetic acid monoester reacts with impurity A in cisatracurium besylate, adds a solvent, stirs, and filters to obtain impurity W crystallization, and dry to obtain final product impurity W. The cisatracurium besylate impurity W prepared by the present invention has high purity, and the preparation method is simple, and the prepared impurity W can be directly used as a standard for the quantitative detection process of the impurity W in the cisatracurium besylate.

The present invention belongs to the technical field of medicine, and particularly relates to a cisatracurium besylate composition for injection, wherein the cisatracurium besylate composition comprises 2.0 mg / mL of cisatracurium besylate, 0.8-1.5 mg / mL of methionine, 1.0-2.0 mg / mL of vitamin C, an appropriate amount of a pH value adjusting agent, and 1000 mL of water for injection. According to the present invention, vitamin C provides the anti-oxidation effect, and methionine can increase the glutathione content in vivo so as to activate acetylcholinesterase, reduce the concentration of acetylcholine, and promote the combination between cisatracurium besylate and cholinergic receptors, such that the prepared pharmaceutical composition has advantages of good stability and excellent efficacy.

The present invention provides an improved method for obtaining cisatracurium besylate, which preferably chromatographically separating cisatracurium besylate from a mixture of (1R,1′R)-atracurium isomers via flash chromatography.

The invention relates to a preparation method of a tetrahydrobenzyl isoquinoline compound, which is characterized in that the method comprises the step of adding a specific chiral organic acid into a mixture containing a compound shown as a formula (I) to form a salt, and the chemical purity and optical purity of the prepared product of the compound shown as the formula (I) are greatly improved while the high yield is ensured. The method is favorable for improving the total yield and controlling the product quality in the synthesis process of the mivacurium chloride or cisatracurium besylate finished product, provides a powerful guarantee for improving the safety and effectiveness of the finished product medicine, and is suitable for industrial production.

The invention relates to a kind of cisatracurium besylate for injection used for storage and transportation at 25°C and its preparation and freeze-drying production process. The specific formula of cisatracurium besylate for injection is as follows: Tracuronium 10-20mg; Dextran-20 50mg; Mannitol 50mg; Solution containing 20% ​​benzenesulfonic acid to adjust PH; Water for injection 2000-3000ml. The freeze-drying production process includes: pre-freezing, sublimation drying, re-drying, plugging and capping. The freeze-drying production process in the present invention improves the chemical stability of the medicine, can be stored, transported and used at 25°C, ensures product quality, reduces storage and transportation conditions for finished products, and improves product quality. It is of great importance in the field of medical applications. significance.

The invention discloses a preparation method of a cisatracurium besylate intermediate. The method is as follows: compound III is freed by adding alkali, reacts with tert-butyl acrylate under the catalysis of acetic acid, and then adds oxalic acid to form a salt to obtain the compound of formula VI; compound of formula VI is freed by adding alkali, and then firstly becomes salt, and then hydrolyze the tert-butyl ester in it into carboxylic acid under heating to obtain the compound of formula VII, and then carry out esterification reaction with 1,5-pentanediol in situ to generate an esterified product, after washing the excess compound of formula VII with water, add Alkali alkalization, and then salify with oxalic acid to obtain the intermediate of formula IV. The product of the present invention has high yield and high purity, can be directly put into the cisatracurium besylate for the last step reaction without refining to finally obtain the cisatracurium besylate, and has simple aftertreatment and is easy for industrialized production.