Preparation method of cisatracurium besilate injection without preservatives
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A technology of cisatracurium besylate and injection, which is applied in the field of medicine and can solve the problems of easy generation of impurities and increased content
Inactive Publication Date: 2019-01-04
SHANGHAI PHARMA DONGYING JIANGSU PHARMA CO LTD
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[0004] However, during the storage and transportation of cisatracurium besylate injection, the content of cis-acid, R-laudane base, cis-hydroxy compound and cis-acrylic acid mixture will decrease with time due to the reason of Hofmann degradation. increases with the passage of time, it is easy to produce impurities
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[0018] Find after research: (1) the main degradation impurity of cisatracurium besylate is cis-acid, R-laudane base, cis-hydroxyl compound and cis-acrylic acid mixture, and cis-atracurium besylate is not stable under high temperature conditions. Stable, 60 ℃ treatment 8h, cis-acid, R-laudane base, cis-hydroxy compound and cis-acrylic acid mixture increased by 1.11%, 5.15%, 1.40% and 4.65%, respectively.
[0019] (2) cisatracurium besylate is unstable under acidic conditions. After being treated with 0.1mol / L hydrochloric acid, the content of R-laudansine rises to 16.2%, but it is extremely unstable under alkaline conditions and can be neutralized immediately , R-laudanline increased by 8.87%, and the content of cis-acrylic acid mixture was 6.03%. Choosing an appropriate pH is beneficial to ensure the stability of cisatracurium besylate injection.
[0020] (3) cisatracurium besylate is relatively stable under oxidation conditions, 30% H 2 o 2 conditions, the cis-acid and cis-...
specific Embodiment 1
[0026] Element
[0027] The preparation method is: measure about 850g of water for injection, adjust the pH to 3.4-3.6 with benzenesulfonic acid solution I, keep warm at 2°C-8°C to obtain solution A, add the prescribed amount of cisatracurium besylate into solution A , stir and dissolve to obtain solution B, adjust the pH of solution B to 3.0-3.6 with benzenesulfonic acid solution II, add water for injection to 1000.0g, and obtain solution C; pass solution C through a 0.22 μm polyethersulfone membrane, and pour Pack 5ml into a freeze-drying box, vacuumize at 2°C to 8°C, fill with nitrogen, press the stopper, and crimp the cap.
specific Embodiment 2
[0028] Element
[0029] The preparation method is: measure about 850g of water for injection, adjust the pH to 3.4-3.6 with benzenesulfonic acid solution I, keep warm at 2°C-8°C to obtain solution A, add the prescribed amount of cisatracurium besylate into solution A , stir and dissolve to obtain solution B, adjust the pH of solution B to 3.0-3.6 with benzenesulfonic acid solution II, add water for injection to 1000.0g, and obtain solution C; pass solution C through a 0.22 μm polyethersulfone membrane, and pour Pack 5ml into a freeze-drying box, vacuumize at 2°C to 8°C, fill with nitrogen, press the stopper, and crimp the cap.
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Abstract
The invention discloses a preparation method of cisatracurium besilate injection without preservatives. Each 1000ml of injection is prepared from the following components by weight proportion: 2 to 10g of cisatracurium besilate and proper amount of benzenesulfonic acid. The preparation method comprises the following steps: a, adding 85 percent of prescription volume of injection water into a preparation container, adjusting the pH by using a benzenesulfonic acid solution I, insulating, adding the cisatracurium besilate and stirring until the solution is clarified; b, adjusting the pH of the clarified solution obtained in the first step by using a benzenesulfonic acid solution II, determining the volume with injection water and finishing preparation; c, after the preparation of liquid medicine is finished, carrying out aseptic filtration and canning, feeding into a freeze-dying chassis, insulating, vacuumizing, charging nitrogen and carrying out compression tamponinging, thus obtaininga final product. According to the preparation method disclosed by the invention, the effect of the temperature on the product quality during the preparation process of the cisatracurium besilate injection is controlled as much as possible, so that impurities of the cisatracurium besilate injection do not exceed the standards within the validity period.
Description
technical field [0001] The invention relates to the technical field of medicine, in particular to a method for preparing preservative-free cisatracurium besylate injection. Background technique [0002] The original research company of cisatracurium besylate is AbbVie, and its published product manual states that its prescription ingredients contain 2 mg of cisatracurium per ml, and besylate adjusts the pH of the liquid to 3.0-3.8. But the preparation method of besylate cisatracurium injection is not disclosed. [0003] Patent CN1070499364 discloses a preparation method of besylate cisatracurium injection, the preparation process is as follows: take water for injection, fill it with nitrogen to keep the dissolved oxygen in the water lower than 1ppm, and then use benzenesulfonic acid solution to dissolve the Adjust the pH value of water for injection to 3.9-4.1, add cisatracurium besylate and benzyl alcohol, and mix until the solution is clear; use benzenesulfonic acid solut...
Claims
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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/08A61K31/4725A61K47/20
CPCA61K9/0019A61K9/08A61K31/4725A61K47/20
Inventor 汤征王小镒杜芳周敏慧邓席云葛卫峰丁云晖
Owner SHANGHAI PHARMA DONGYING JIANGSU PHARMA CO LTD
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