Meclocycline injection which can be terminally sterilized, its preparation process and use

Abstract

The application discloses a terminal sterilization mivacurium chloride injection, which comprises mixed solute mivacurium chloride and solvent injection water, and the concentration is 2.14 mg / ml, and the pH value of the mivacurium chloride injection is 3.2-3.8. Under the condition of the specific pH value, the degradation speed of the mivacurium chloride is slowed down, and the mivacurium chloride injection preparation can be subjected to high-temperature terminal sterilization. After sterilization, the impurity level of the preparation is still in a low state, so that no additional stabilizer excipient needs to be added, the stability of the mivacurium chloride injection is improved, the high-temperature sterilization operation can be tolerated, the preparation microorganism and endotoxin level are effectively controlled, and the safety of clinical medication is improved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparations, specifically to a terminally sterilizable micuronium chloride injection, its preparation process, and its uses. Background Technology

[0002] Micuronium chloride injection, developed by Abbott Lab, was first marketed in the United States in 1992. Its chemical name is (R)-1,2,3,4-tetrahydro-2-(3-hydroxypropyl)-6,7-dimethoxy-2-methyl-1-(3,4,5-trimethylbenzyl)isoquinoline chloride (E)-4-octenedicarboxylic acid. Micuronium chloride injection is a non-depolarizing neuromuscular blocking agent, primarily used clinically as an adjunct to general anesthesia to relax skeletal muscles, facilitating endotracheal intubation and mechanical ventilation. It has advantages such as rapid onset of action, short duration of action, rapid recovery, and no cumulative effect, and possesses broad market prospects.

[0003] Currently available products use micudium chloride as raw material, which is then dissolved and hydrochloric acid is added to adjust the pH to around 4.5. For example, patent application number 202210509896.0, entitled "A Micudium Chloride Injection Stable at 25℃ and Its Preparation Method and Use," uses micudium chloride as raw material, which is then dissolved and hydrochloric acid is added to adjust the pH to 3.9-4.0. Because micudium chloride has poor stability in water, it is easily degraded to produce impurities A, B, C, and D. According to clinical research results, the content of these impurities has a significant impact on the quality and clinical efficacy of micudium chloride.

[0004] Therefore, to avoid or delay the degradation of micuronium chloride, current commercially available products are manufactured using non-terminal sterilization filtration processes and stored at 2–8°C. However, the following problems exist: 1. Micuronium chloride has poor stability in water and cannot withstand high temperatures, easily degrading and producing impurities. High impurity content negatively impacts product safety. While some patents suggest using high-quality raw materials, such as freeze-dried micuronium chloride formulations, or excipients like propylene glycol, reduced glutathione, and acetic acid to improve formulation stability, these either involve excessive equipment investment increasing production costs or the addition of excessive excipients, posing risks to clinical drug safety. 2. Commercially available formulations are manufactured using sterilization filtration processes and stored at 2–8°C to ensure the lowest possible impurity levels. However, due to the chosen manufacturing process, high cleanliness and strict monitoring are required in the production workshop, increasing the risk of microbial contamination and reducing clinical drug safety. Summary of the Invention

[0005] In view of the above-mentioned shortcomings of the prior art, the purpose of this invention is to provide a terminally sterilizable micuronium chloride injection, its preparation process and uses, which solves the problems of high impurity content and easy microbial contamination in the prior art, which affect the quality and safety of the drug.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A terminally sterilizable micudium chloride injection comprises a mixture of micudium chloride solute and water for injection solvent, with a concentration of 2.14 mg / ml, and the pH value of the micudium chloride injection is 3.2-3.8. The micudium chloride injection formulation is terminally sterilized at high temperature.

[0008] Preferably, the pH value of the micudium chloride injection solution is adjusted using hydrochloric acid solution.

[0009] Preferably, the micuronium chloride injection formulation is sterilized at 121°C for 12 minutes to reduce the risk of microbial invasion.

[0010] Preferably, the temperature of the water for injection is 20–40°C.

[0011] Preferably, the formulation process steps of the micuronium chloride injection are as follows:

[0012] S1. Add 95% of the total amount of water for injection to the preparation container. The temperature of the water for injection should be 20-40℃.

[0013] S2. Add the prescribed amount of micuronium chloride to the water for injection obtained in step S1, stir with a mixer until completely dissolved, adjust the pH to 3.2-3.8 with hydrochloric acid solution, and add water for injection to the final volume to obtain micuronium chloride injection solution.

[0014] S3. Filter the micuronium chloride injection solution from step S2 through a 0.22μm filter cartridge;

[0015] S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule and sterilize it at 121℃ for 12min.

[0016] S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

[0017] Preferably, in step S2, the stirring speed of the mixer is 150-160 r / min, the stirring time is 20 min, and after adding water for injection to the total volume, the stirring continues for 5 min to cool down to below 30°C.

[0018] This invention also provides a formulation process for a terminally sterilizable micuronium chloride injection, characterized by comprising the following steps:

[0019] S1. Add 95% of the total amount of water for injection to the preparation container;

[0020] S2. Add the prescribed amount of micuronium chloride to the water for injection obtained in step S1, stir with a mixer until completely dissolved, adjust the pH to 3.2-3.8 with hydrochloric acid solution, and add water for injection to the final volume to obtain micuronium chloride injection solution.

[0021] S3. Filter the micuronium chloride injection solution from step S2 through a 0.22μm filter cartridge;

[0022] S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule and sterilize it at 121℃ for 12min.

[0023] S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

[0024] Preferably, in step S2, the stirring speed of the mixer is 150-160 r / min, the stirring time is 20 min, and after adding water for injection to the total volume, the stirring continues for 5 min to cool down to below 30°C.

[0025] Preferably, the water temperature for injection is 20–40°C.

[0026] This invention also provides the application of terminally sterilizable micuronium chloride injection in the preparation of adjuvant drugs for general anesthesia.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] This invention, by operating under specific pH conditions of 3.2-3.8, further slows down the decomposition of micuronium chloride injection, reduces impurity content, and improves the stability of micuronium chloride injection. Simultaneously, it can withstand high-temperature sterilization at 121°C for 12 minutes. Experiments have shown that the impurity level of the formulation remains low after sterilization, thus eliminating the need for additional stabilizers or excipients. This achieves the effect of improving the stability of micuronium chloride injection, allowing it to withstand high-temperature sterilization, effectively controlling the levels of microorganisms and endotoxins in the formulation, and improving the safety of clinical use. Furthermore, it does not increase drug production costs, making it more economical. Detailed Implementation

[0029] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0030] Example 1

[0031] A terminally sterilizable micuronium chloride injection comprises 2.14 g of mixed solute micuronium chloride and 1000 ml of solvent water for injection, with the water temperature controlled at 20–40 °C, and approximately 54.0 g of 0.01 mol / L hydrochloric acid solution added. The pH value of the micuronium chloride injection is 3.2. The micuronium chloride injection preparation is terminally sterilized at 121 °C for 12 min.

[0032] The formulation process steps of the micuronium chloride injection are as follows:

[0033] S1. Add 95% of the total amount of water for injection, i.e., 950 ml, to the preparation container. The temperature of the water for injection should be 20-40℃.

[0034] S2. Add 2.14g of micuronium chloride to the water for injection obtained in step S1. Stir with a mixer at a speed of 150-160 r / min for 20 min until completely dissolved. Adjust the pH to 3.2 with 54.0g of 0.01mol / L hydrochloric acid solution. Add water for injection to a final volume of 1000ml and continue stirring for 5 min to cool down to below 30℃.

[0035] S3. Filter the micudium chloride injection solution from step S2 through a 0.22μm filter element to obtain the micudium chloride injection solution; the filter element is a polyethersulfone filter membrane.

[0036] S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule and sterilize it at 121℃ for 12min.

[0037] S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

[0038] Example 2

[0039] A terminally sterilizable micuronium chloride injection solution comprises 2.14 g of mixed solute micuronium chloride and 1000 ml of solvent water for injection, with the water temperature controlled at 20–40 °C, and approximately 31.0 g of 0.01 mol / L hydrochloric acid solution added. The pH value of the micuronium chloride injection solution is 3.5. The micuronium chloride injection solution preparation is terminally sterilized at 121 °C for 12 min.

[0040] The formulation process steps of the micuronium chloride injection are as follows:

[0041] S1. Add 95% of the total amount of water for injection, i.e., 950 ml, to the preparation container. The temperature of the water for injection should be 20-40℃.

[0042] S2. Add 2.14g of micuronium chloride to the water for injection obtained in step S1. Stir with a mixer at a speed of 150-160 r / min for 20 min until completely dissolved. Adjust the pH to 3.5 with 31.0g of hydrochloric acid solution. Add water for injection to a final volume of 1000ml and continue stirring for 5 min to cool down to below 30℃.

[0043] S3. Filter the micudium chloride injection solution from step S2 through a 0.22μm filter element to obtain the micudium chloride injection solution; the filter element is a polyethersulfone filter membrane.

[0044] S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule and sterilize it at 121℃ for 12min.

[0045] S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

[0046] Example 3

[0047] A terminally sterilizable micuronium chloride injection solution comprises 2.14 g of mixed solute micuronium chloride and 1000 ml of solvent water for injection, with the water temperature controlled at 20–40 °C, and approximately 19.6 g of 0.01 mol / L hydrochloric acid solution added. The pH value of the micuronium chloride injection solution is 3.8. The micuronium chloride injection solution preparation is terminally sterilized at 121 °C for 12 min.

[0048] The formulation process steps of the micuronium chloride injection are as follows:

[0049] S1. Add 95% of the total amount of water for injection, i.e., 950 ml, to the preparation container. The temperature of the water for injection should be 20-40℃.

[0050] S2. Add 2.14g of micuronium chloride to the water for injection obtained in step S1. Stir with a mixer at a speed of 150-160 r / min for 20 minutes until completely dissolved. Adjust the pH to 3.8 with 19.6g of hydrochloric acid solution. Add water for injection to a final volume of 1000ml and continue stirring for 5 minutes to cool down to below 30℃.

[0051] S3. Filter the micudium chloride injection solution from step S2 through a 0.22μm filter element to obtain the micudium chloride injection solution; the filter element is a polyethersulfone filter membrane.

[0052] S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule and sterilize it at 121℃ for 12min.

[0053] S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

[0054] Comparative Example 4

[0055] A terminally sterilizable micuronium chloride injection comprises 2.14 g of mixed solute micuronium chloride and 1000 ml of solvent water for injection, with the water temperature controlled at 20–40 °C, and approximately 13.0 g of 0.01 mol / L hydrochloric acid solution added. The pH value of the micuronium chloride injection is 3.9. The micuronium chloride injection preparation is terminally sterilized at 121 °C for 12 min.

[0056] The formulation process steps of the micuronium chloride injection are as follows:

[0057] S1. Add 95% of the total amount of water for injection, i.e., 950 ml, to the preparation container. The temperature of the water for injection should be 20-40℃.

[0058] S2. Add 2.14g of micuronium chloride to the water for injection obtained in step S1. Stir with a mixer at a speed of 150-160 r / min for 20 minutes until completely dissolved. Adjust the pH to 3.9 with 13.0g of hydrochloric acid solution. Add water for injection to a final volume of 1000ml and continue stirring for 5 minutes to cool down to below 30℃.

[0059] S3. Filter the micudium chloride injection solution from step S2 through a 0.22μm filter element to obtain the micudium chloride injection solution; the filter element is a polyethersulfone filter membrane.

[0060] S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule and sterilize it at 121℃ for 12min.

[0061] S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

[0062] Comparative Example 5

[0063] A terminally sterilizable micudium chloride injection solution comprises 2.14 g of mixed solute micudium chloride and 1000 ml of solvent water for injection, with the water temperature controlled at 20–40 °C, and approximately 10.5 g of 0.01 mol / L hydrochloric acid solution added. The pH value of the micudium chloride injection solution is 4.0. The micudium chloride injection solution preparation is terminally sterilized at 121 °C for 12 min.

[0064] The formulation process steps of the micuronium chloride injection are as follows:

[0065] S1. Add 95% of the total amount of water for injection, i.e., 950 ml, to the preparation container. The temperature of the water for injection should be 20-40℃.

[0066] S2. Add 2.14g of micuronium chloride to the water for injection obtained in step S1. Stir with a mixer at a speed of 150-160 r / min for 20 minutes until completely dissolved. Adjust the pH to 4.0 with 10.5g of hydrochloric acid solution. Add water for injection to a final volume of 1000ml and continue stirring for 5 minutes to cool down to below 30℃.

[0067] S3. Filter the micudium chloride injection solution from step S2 through a 0.22μm filter element to obtain the micudium chloride injection solution; the filter element is a polyethersulfone filter membrane.

[0068] S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule and sterilize it at 121℃ for 12min.

[0069] S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

[0070] Comparative Example 6

[0071] A terminally sterilizable micuronium chloride injection comprises 2.14 g of mixed solute micuronium chloride and 1000 ml of solvent water for injection, with the water temperature controlled at 20–40 °C, and approximately 6.2 g of 0.01 mol / L hydrochloric acid solution added. The pH value of the micuronium chloride injection is 4.5. The micuronium chloride injection formulation is terminally sterilized at 121 °C for 12 min.

[0072] The formulation process steps of the micuronium chloride injection are as follows:

[0073] S1. Add 95% of the total amount of water for injection, i.e., 950 ml, to the preparation container. The temperature of the water for injection should be 20-40℃.

[0074] S2. Add 2.14g of micuronium chloride to the water for injection obtained in step S1. Stir with a mixer at a speed of 150-160 r / min for 20 minutes until completely dissolved. Adjust the pH to 4.5 with 6.2g of hydrochloric acid solution. Add water for injection to a final volume of 1000ml and continue stirring for 5 minutes to cool down to below 30℃.

[0075] S3. Filter the micudium chloride injection solution from step S2 through a 0.22μm filter element to obtain the micudium chloride injection solution; the filter element is a polyethersulfone filter membrane.

[0076] S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule and sterilize it at 121℃ for 12min.

[0077] S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

[0078] Comparative Example 7

[0079] A micuronium chloride injection solution, the formulation of which includes 2.14g of mixed solute micuronium chloride and 1000ml of solvent water for injection, the water temperature of which is controlled at 20-40℃, and about 6.2g of hydrochloric acid solution with a concentration of 0.01mol / L added, and the pH value of the micuronium chloride injection solution is 4.5.

[0080] The formulation process steps of the micuronium chloride injection are as follows:

[0081] S1. Add 95% of the total amount of water for injection, i.e., 950 ml, to the preparation container. The temperature of the water for injection should be 20-40℃.

[0082] S2. Add 2.14g of micuronium chloride to the water for injection obtained in step S1. Stir with a mixer at a speed of 150-160 r / min for 20 minutes until completely dissolved. Adjust the pH to 4.5 with 6.2g of hydrochloric acid solution. Add water for injection to a final volume of 1000ml and continue stirring for 5 minutes to cool down to below 30℃.

[0083] S3. Filter the micudium chloride injection solution from step S2 through a 0.22μm filter element to obtain the micudium chloride injection solution; the filter element is a polyethersulfone filter membrane.

[0084] S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule;

[0085] S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

[0086] Comparative Example 8

[0087] A micuronium chloride injection solution, the formulation of which includes 2.14g of mixed solute micuronium chloride and 1000ml of solvent water for injection, the water temperature of which is controlled at 20-40℃, and about 2.0g of hydrochloric acid solution with a concentration of 0.01mol / L is added, and the pH value of the micuronium chloride injection solution is 5.0.

[0088] The formulation process steps of the micuronium chloride injection are as follows:

[0089] S1. Add 95% of the total amount of water for injection, i.e., 950 ml, to the preparation container. The temperature of the water for injection should be 20-40℃.

[0090] S2. Add 2.14g of micuronium chloride to the water for injection obtained in step S1. Stir with a mixer at a speed of 150-160 r / min for 20 minutes until completely dissolved. Adjust the pH to 5.0 with 2.0g of hydrochloric acid solution. Add water for injection to a final volume of 1000ml and continue stirring for 5 minutes to cool down to below 30℃.

[0091] S3. Filter the micudium chloride injection solution from step S2 through a 0.22μm filter element to obtain the micudium chloride injection solution; the filter element is a polyethersulfone filter membrane.

[0092] S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule;

[0093] S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

[0094] Comparative Example 9

[0095] A micuronium chloride injection solution, the formulation of which includes 2.14g of mixed solute micuronium chloride and 1000ml of solvent water for injection, the water temperature of which is controlled at 20-40℃, and about 0.5g of hydrochloric acid solution with a concentration of 0.01mol / L is added, and the pH value of the micuronium chloride injection solution is 5.5.

[0096] The formulation process steps of the micuronium chloride injection are as follows:

[0097] S1. Add 95% of the total amount of water for injection, i.e., 950 ml, to the preparation container. The temperature of the water for injection should be 20-40℃.

[0098] S2. Add 2.14g of micuronium chloride to the water for injection obtained in step S1. Stir with a mixer at a speed of 150-160 r / min for 20 minutes until completely dissolved. Adjust the pH to 5.5 with 0.5g of hydrochloric acid solution. Add water for injection to a final volume of 1000ml and continue stirring for 5 minutes to cool down to below 30℃.

[0099] S3. Filter the micudium chloride injection solution from step S2 through a 0.22μm filter element to obtain the micudium chloride injection solution; the filter element is a polyethersulfone filter membrane.

[0100] S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule;

[0101] S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

[0102] In summary, the group composition of Micuronium Chloride Injection in Examples 1-3 and Comparative Examples 4-9 is shown in the table below:

[0103]

[0104]

[0105] The impurities of the above-mentioned embodiments, comparative samples, and original Micocium chloride preparation were tested, and the results are shown in Table 1 below.

[0106] Table 1. Impurities in Micuronium Chloride Injection

[0107]

[0108] Among them, impurities A, B, C and D are existing technologies as described in application number 202210509896.0, and will not be described in detail here.

[0109] According to the results in Table 1, when using the formulation and preparation process in Examples 1-3 of this invention and the same high-temperature sterilization conditions as Comparative Examples 4-6, it can be seen that, when comparing only the different pH conditions and without considering high-temperature sterilization, the total amount of impurities in this invention is significantly lower than that in Comparative Examples 4-9 and the original product when using Examples 1-3 of this invention at pH 3.2-3.8.

[0110] Under different pH conditions and the same high-temperature sterilization conditions, the total amount of impurities produced by the prepared micudium chloride solution under the conditions of pH 3.2 to 3.8 in Examples 1-3 of the present invention is significantly less than the total amount of impurities produced under the conditions of pH 3.9 to 4.5 in Comparative Examples 4-6.

[0111] Compared with Comparative Examples 7-9 and the original product, the sterilization results of Examples 1-3 of this invention showed slightly higher levels of impurities under different pH conditions and whether or not high-temperature sterilization was used.

[0112] Therefore, in summary, the total impurity content of the micuronium chloride solution prepared using the formulation and manufacturing process of this invention, after high-temperature sterilization, is slightly higher than that of commercially available products without high-temperature sterilization. However, the impurity level of the preparation remains low after sterilization, thus eliminating the need for additional stabilizers or excipients. This achieves the effect of improving the stability of micuronium chloride injection. High-temperature sterilization effectively controls the levels of microorganisms and endotoxins in the preparation, improving the safety of clinical use. Simultaneously, it does not increase drug production costs, making it more economical. Furthermore, by selecting the optimal pH conditions, the total impurity content is also minimized and optimized under the same high-temperature conditions.

[0113] The products sterilized at high temperature in Examples 1-3 of this invention, along with Comparative Examples 4-9 and the original research product, were placed at 40°C for 30 days. Samples were taken at 10 and 30 days to detect changes in impurities. The results are shown in Table 2.

[0114] Table 2. Experimental Results of Influencing Factors

[0115]

[0116]

[0117] Note: All increases in impurities are compared to day 0.

[0118] Table 2 shows that the degradation rate of the micuronium chloride injection of the present invention (Examples 1-3) is significantly reduced under high temperature conditions (40°C), and its impurity growth is significantly lower than that of the micuronium chloride injections of Comparative Examples 4-9, and also lower than the impurity growth of the original product. When the pH of the injection solution is 4.5, 5.0, and 5.5 (Comparative Examples 7, 8, and 9), after being placed at 40°C for 30 days, the impurity growth exceeds 6%. This demonstrates that when the pH of the injection solution of the present invention is in the range of 3.2-3.8, the impurity level of the micuronium chloride injection is significantly lower than that of commercially available products, and the stability is significantly improved.

[0119] The micuronium chloride injections of Examples 1-3 and Comparative Examples 4-7 of this invention and the original research products were placed at 25°C for 6 months, and samples were taken at 3 months and 6 months to detect the changes in impurities. The results are shown in Table 3.

[0120] Table 3 Results of accelerated stability test

[0121]

[0122] Note: All increases in impurities are compared to day 0.

[0123] As shown in Table 3, under accelerated conditions at 25°C, after 6 months of storage, the increase in impurities in the micuronium chloride injection of the present invention was significantly lower than that in the comparative example. The increase in impurities in the product of the present invention was even significantly lower than that in the original product. This indicates that by controlling the pH within a specific range (3.2–3.8) according to the formulation and preparation process of the present invention, the stability of the micuronium chloride injection was significantly improved, the generation of impurities was reduced, terminal sterilization was possible, and the safety and effectiveness of clinical use were improved.

[0124] Based on the disclosure and teachings of the above specification, those skilled in the art can make changes and modifications to the above embodiments. Therefore, the present invention is not limited to the specific embodiments disclosed and described above, and some modifications and changes to the present invention should also fall within the protection scope of the claims of the present invention. Furthermore, although some specific terms are used in this specification, these terms are only for convenience of explanation and do not constitute any limitation on the present invention. Other devices that are the same as or similar to these terms are all within the protection scope of the present invention.

Claims

1. A terminally sterilizable micuronium chloride injection solution, characterized in that, The solution comprises a mixture of micuronium chloride as a solute and water for injection as a solvent, with a concentration of 2.14 mg / ml. The temperature of the water for injection is 20-40°C, and the pH value of the micuronium chloride injection solution is 3.2-3.

8. The pH value of the micuronium chloride injection solution is adjusted with hydrochloric acid solution. This micuronium chloride injection solution is subjected to high-temperature terminal sterilization at 121°C for 12 minutes, which can reduce the risk of microbial invasion. The formulation process steps of the micuronium chloride injection are as follows: S1. Add 95% of the total amount of water for injection to the preparation container. The temperature of the water for injection should be 20~40℃. S2. Add the prescribed amount of micuronium chloride to the water for injection obtained in step S1, and stir with a mixer at a speed of 150-160 r / min for 20 min until completely dissolved. Then add water for injection to the final volume and continue stirring for 5 min to cool down to below 30°C. Adjust the pH to 3.2-3.8 with hydrochloric acid solution, and add water for injection to the final volume to obtain micuronium chloride injection solution. S3. Filter the micuronium chloride injection solution from step S2 through a 0.22μm filter cartridge; S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule and sterilize it at 121℃ for 12min. S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

2. The formulation process of a terminally sterilizable micuronium chloride injection as described in claim 1, characterized in that, Includes the following steps: S1. Add 95% of the total amount of water for injection to the preparation container. The temperature of the water for injection should be 20~40℃. S2. Add the prescribed amount of micuronium chloride to the water for injection obtained in step S1, and stir with a mixer at a speed of 150-160 r / min for 20 min until completely dissolved. Then add water for injection to the final volume and continue stirring for 5 min to cool down to below 30°C. Adjust the pH to 3.2-3.8 with hydrochloric acid solution, and add water for injection to the final volume to obtain micuronium chloride injection solution. S3. Filter the micuronium chloride injection solution from step S2 through a 0.22μm filter cartridge; S4. Fill the solution obtained in step S3 into a 5ml borosilicate glass ampoule and sterilize it at 121℃ for 12min. S5. Perform quality inspection on the micuronium chloride injection solution obtained in step S4 to detect its impurity content.

3. The application of the terminally sterilizable micuronium chloride injection as described in claim 1 in the preparation of adjuvant drugs for general anesthesia.

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