CN111374942B - Steroid muscle relaxant injection and preparation method thereof - Google Patents

Abstract

The invention belongs to the technical field of medicinal preparations, and particularly provides a steroid muscle relaxant injection which comprises active ingredients, a buffer solution, a pH regulator, an osmotic pressure regulator and polyethylene glycol 1000 vitamin E succinate, wherein two buffer systems are adopted in the preparation process to control the change of the pH value of the solution. The invention selects proper prescription components and preparation method, and avoids the increase of related substances in the production and storage process of the injection to the maximum extent. The steroid muscle relaxant injection prepared by the invention has stable and uniform quality, excellent safety and compliance, green and economic preparation process and suitability for industrial production.

Description

Steroid muscle relaxant injection and preparation method thereof

Technical Field

The invention belongs to the technical field of medicinal preparations, and particularly relates to a steroid muscle relaxant injection and a preparation method thereof.

Background

Rocuronium Bromide (Rocuronium Bromide) is a widely used steroid non-depolarizing muscle relaxant with rapid onset of action and moderate potency, and is used clinically as an adjuvant for conventional endotracheal intubation for general anesthesia. Contains propenyl on the active quaternary nitrogen atom, and has the following molecular structure:

rocuronium bromide is unstable to alkali, heat and other conditions in water, and the accelerated degradation reaction comprises hydrolysis, thermal degradation, photodegradation and oxidative degradation. The pH value of the original preparation Aikosong (Emeron) is 3.8-4.2, the storage period is 2 years at the temperature of 2-8 ℃, and the storage period is 60 days at the temperature of 25 ℃. The rocuronium bromide injection is affected by sterilization temperature and time, solution pH value, storage time, light, metal ions and other factors in the preparation process, so that according to the stipulations of European pharmacopoeia and Chinese pharmacopoeia 2015 edition, related substances A, B, C, D, E, F, G, H and unknown impurities of the injection are checked, the stipulation limit of total impurities is less than 2.0%, the limit of impurity C is less than 1.5%, other single impurities are less than 0.1%, and other unknown impurities are less than 0.5%. The related substances and structural changes of rocuronium bromide are shown in the following table:

the presence of impurities, even in small amounts, can affect the effectiveness and safety of pharmaceutical products, and therefore impurity analysis has become an important component of the research of drug development processes. Various regulatory agencies, such as the international harmonization for drug registration technology (ICH) and the Food and Drug Administration (FDA), recommend reporting impurities that exceed allowable limits. The ICH impurity guidelines state that all degradation products formed by pharmaceutical products are characterized at levels greater than or equal to 0.1%.

WO2008/065142 discloses the addition of sulfoalkyl ether- β -cyclodextrin derivatives or pharmaceutically acceptable salts thereof to an aqueous solution containing rocuronium bromide to stabilize rocuronium bromide. To reduce injection pain, the pH should be in the range of 3.5-7.5, preferably 4-5. It has been reported that sulfoalkyl ether- β -cyclodextrin derivatives or pharmaceutically acceptable salts thereof may cause renal dysfunction.

CN201310410100.7 discloses a stable rocuronium bromide injection formulation and its preparation method, wherein the stabilizer is selected from phosphate buffer or citrate buffer, and the pH range is preferably 3.0-5.0. The pH regulator is selected from inorganic acid, organic acid, and/or inorganic base. The osmotic pressure regulator is preferably sodium chloride. The preparation method comprises adding stabilizer and osmotic pressure regulator into water for injection, adding rocuronium bromide, adjusting pH to 3.0-5.0 with appropriate pH regulator, adding active carbon, quantifying, filtering, sterilizing, bottling, pressing, and capping. The rocuronium bromide injection prepared by the method is stored at normal temperature, and the impurity content changes rapidly.

CN201210364536.2 discloses a preparation method of rocuronium bromide injection, which comprises the steps of dissolving 25 ℃ water for injection with a prescribed amount of sodium acetate, adjusting the pH value to 3.8-4.2 with glacial acetic acid, adding a prescribed amount of rocuronium bromide bulk drug to dissolve, adjusting the pH value to 3.8-4.2 with glacial acetic acid, adding sodium chloride to adjust the solution to be isotonic, filtering and sterilizing, filling, corking, capping, and sterilizing at 115 ℃ for 35min under hot pressure. The injection obtained by the method is placed for 10 days, and the related substances reach 2.85%.

CN200910177540.6 discloses a stable rocuronium bromide injection for intravenous administration, wherein a buffer system adopts citrate or acetate with pH value of 3.8-4.0, and adopts sodium calcium edetate or disodium edetate as a stabilizer. The preparation process comprises the steps of dissolving the citric acid with the prescription amount by adding the water for injection with the prescription amount of more than 80 percent, adding the sodium hydroxide to adjust the pH value to be within 4.0, sequentially adding the stabilizer and the raw material medicine, stirring and dissolving, adjusting the pH value to be 3.8-4.0, performing an activated carbon process, quantifying, filling, plugging, capping, and performing hot-pressing sterilization at 115 ℃ for 30 min. The prepared injection has the advantage of rapid increase of impurity content in the storage process.

CN201480076036.6 discloses a rocuronium bromide preparation with excellent stability, wherein the buffer solution is selected from citric acid-sodium hydroxide buffer solution, tartaric acid-sodium hydroxide buffer solution, potassium hydrogen phthalate-hydrochloric acid buffer solution, glycine-hydrochloric acid buffer solution, etc., preferably 0.1M glycine-hydrochloric acid buffer solution, the pH value of the preparation is adjusted to be below 3.5, too low pH has large irritation to human body, if stored for 6 months under the condition of controlling pH to be 4.0, the impurity C reaches 5.46%, and how to ensure the stability of rocuronium bromide when the pH is raised to reduce irritation is not reported.

CN201210501837.5 discloses an injection containing rocuronium bromide, which maintains the pH value of a system to be 4.0-5.0 through 1% -5% acetate buffer solution, improves the stability of a main drug, and is sterilized by hot pressing at 121 ℃ for 15min, although the generation of impurity C is reduced to a certain extent, the impurity content is increased rapidly in the long-term storage process.

CN201610061810.7 discloses a preparation method of rocuronium bromide injection of muscle relaxant, which comprises the steps of dissolving sorbitol, ammonium methosulfate and ammonium acetate in the prescribed amount with water for injection, then carrying out an activated carbon process, keeping the temperature of filtrate at 85-90 ℃ for 5-15min, adding rocuronium bromide raw material, adjusting the pH value to 6.0-6.5 with glacial acetic acid, carrying out filtration sterilization, filling nitrogen into liquid medicine, filling the liquid medicine into a brown ampoule bottle, and carrying out autoclaving at 121 ℃ for 10-20min, wherein the content of impurity C in the prepared rocuronium bromide injection is obviously increased in the long-term storage process.

CN201380042469.5 discloses a stable aqueous composition of rocuronium bromide, excipient is selected from D-gluconic acid, lactone of gluconic acid or mixture thereof, buffer is selected from buffer based on citrate and acetate, preferably pH value is 3.8-4.0, which can not solve the problem of stability of rocuronium bromide injection.

CN200910075875.7 discloses a preparation method of rocuronium bromide injection, which comprises cooling water for injection to room temperature, adding acetic acid-sodium acetate buffer solution, and mixing well. Dissolving the sodium chloride and rocuronium bromide according to the prescription amount, adjusting the pH value to 4.0 by using 1mol/L acetic acid solution, performing activated carbon process, filtering and sterilizing, filling, pressing and capping, and performing hot-pressing sterilization at 121 ℃ for 20min to obtain the injection with poor stability and excessive impurity content.

The rocuronium bromide varieties reported in the literature and on the market at present mainly adopt water injection, and the rocuronium bromide is found to be unstable and extremely easy to hydrolyze in practical application, so that the rocuronium bromide is required to be stored at 2-8 ℃. The content of related substances of the existing rocuronium bromide injection is obviously increased along with the prolonging of time in the storage and transportation processes. Therefore, in order to improve the medication safety and the drug stability and reduce the condition requirement of drug storage, new rocuronium bromide injection must be further developed.

Disclosure of Invention

Based on the defects and research and development difficulties in the prior art, in order to avoid increase of related substances in the injection production and storage processes to the maximum extent, the inventor provides a formula of rocuronium bromide injection, selects a proper buffer solution, and then adds polyethylene glycol 1000 vitamin E succinate as a stabilizer, so that the stability of the rocuronium bromide injection can be remarkably improved, and the generation of related substances is reduced.

The amino acid-hydrochloric acid buffer solution and the organic acid salt buffer solution are used in combination, so that the generation of insoluble particles can be reduced, the vascular irritation reaction and the injection pain can be effectively relieved, and the generation of related substances can be reduced. The polyethylene glycol 1000 vitamin E succinate has larger molecular volume and molecular surface area, the molecular structure comprises a long polyethylene glycol chain and a lipophilic vitamin E group, and the polyethylene glycol 1000 vitamin E succinate can be used as a stabilizer in rocuronium bromide injection to provide stronger steric hindrance and potential steric hindrance and better prevent the nucleophilic attack of an affinity group with high electronegativity of hydroxide ions on rocuronium bromide unstable groups. And the buffer solution of the two buffer systems and the polyethylene glycol 1000 vitamin E succinate are combined, so that the generation of related substances, particularly impurity C, is reduced to a greater extent, the stability of the rocuronium bromide injection is improved, and the administration safety and the compliance are more excellent.

The injection is realized by the following scheme:

a steroid muscle relaxant injection comprises rocuronium bromide, buffer solution, pH regulator, osmotic pressure regulator, and polyethylene glycol 1000 vitamin E succinate.

The buffer solution is an amino acid-hydrochloric acid buffer solution.

Preferably, the buffer solution is one of glycine-hydrochloric acid and alanine-hydrochloric acid.

The pH regulator is one of acetate buffer solution, citrate buffer solution, mesylate buffer solution, tartrate buffer solution and succinate buffer solution.

Preferably, the pH regulator is one of tartrate buffer and succinate buffer.

The osmotic pressure regulator is sodium chloride.

The pH value of the steroid muscle relaxant injection is 3.5-5.0.

The steroid muscle relaxant injection comprises the following specific components in percentage by weight:

the invention also provides a preparation method of the steroid muscle relaxant injection, which specifically comprises the following steps:

(a) preparing a buffer solution with a certain pH value, and measuring the buffer solution with a prescribed amount for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of pH regulator into the solution obtained in the step (c) to regulate the pH value;

(e) adding an osmotic pressure regulator into the solution obtained in the step (d) to regulate the osmotic pressure, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, and packaging.

Preferably, the steroid muscle relaxant injection is prepared by the following steps:

(a) preparing a buffer solution with the pH value of 3.0-4.0, and measuring the buffer solution with the amount according to the prescription for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of pH regulator into the solution obtained in the step (c), and regulating the pH value to 3.5-5.0;

(e) adding an osmotic pressure regulator into the solution obtained in the step (d) to regulate the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing and capping.

The invention selects proper prescription components and a preparation method, avoids the increase of related substances in the production and storage processes of the injection to the maximum extent, and the prepared rocuronium bromide injection has stable and uniform quality, excellent safety and compliance, green and economic preparation process and is suitable for industrial production.

Detailed Description

The invention is further illustrated by the following examples. It should be properly understood that: the examples of the present invention are given solely for the purpose of illustration and not as limitations of the present invention, and therefore, simple modifications of the present invention in the context of the methods of the present invention are intended to fall within the scope of the claims.

Example 1

1) Prescription

2) Preparation process

(a) Preparing a glycine-hydrochloric acid buffer solution with the pH value of 3.5, measuring the buffer solution with the prescription amount, and uniformly mixing for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of succinate buffer solution into the solution obtained in the step (c), and adjusting the pH value to 4.0;

(e) adding sodium chloride into the solution obtained in the step (d) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing, and capping.

Example 2

1) Prescription

2) Preparation process

(a) Preparing alanine-hydrochloric acid buffer solution with the pH value of 3.5, measuring the buffer solution with the prescription amount, and uniformly mixing for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of tartrate buffer solution into the solution obtained in the step (c), and adjusting the pH value to 4.0;

(e) adding sodium chloride into the solution obtained in the step (d) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing and capping.

Example 3

1) Prescription

2) Preparation process

(a) Preparing a proline-hydrochloric acid buffer solution with the pH value of 4.0, and measuring the buffer solution with the amount according to the prescription for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of acetate buffer solution into the solution obtained in the step (c), and adjusting the pH value to 5.0;

(e) adding sodium chloride into the solution obtained in the step (d) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing and capping.

Example 4

1) Prescription

2) Preparation process

(a) Preparing a histidine-hydrochloric acid buffer solution with the pH value of 3.0, and measuring the buffer solution with the prescription amount for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of citrate buffer solution into the solution obtained in the step (c), and adjusting the pH value to 3.5;

(e) adding sodium chloride into the solution obtained in the step (d) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing and capping.

Example 5

1) Prescription

2) Preparation process

(a) Preparing arginine-hydrochloric acid with the pH value of 4.0, and measuring a prescription amount of buffer solution for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of a mesylate buffer solution into the solution obtained in the step (c), and adjusting the pH value to 5.0;

(e) adding sodium chloride into the solution obtained in the step (d) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing and capping.

Example 6

1) Prescription

2) Preparation process

(a) Preparing lysine-hydrochloric acid with the pH value of 5.0, and measuring a prescription amount of buffer solution for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of phosphate buffer solution into the solution obtained in the step (c), and adjusting the pH value to 6.0;

(e) adding sodium chloride into the solution obtained in the step (d) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing and capping.

Example 7

1) Prescription

2) Preparation process

(a) Preparing a succinate buffer solution with a pH value of 4.0, and measuring a prescription amount of the buffer solution for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of succinic acid into the solution obtained in the step (c), and adjusting the pH value to 4.0;

(e) adding sodium chloride into the solution obtained in the step (d) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing, and capping.

Example 8

1) Prescription

2) Preparation process

(a) Preparing an aspartic acid-hydrochloric acid buffer solution with the pH value of 3.5, and measuring the buffer solution with the prescription amount for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of citrate buffer solution into the solution obtained in the step (c), and adjusting the pH value to 4.0;

(e) adding sodium chloride into the solution obtained in the step (d) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing, and capping.

Example 9

1) Prescription

2) Preparation process

(a) Preparing a lysine-hydrochloric acid buffer solution with the pH value of 3.5, and measuring the buffer solution with the prescription amount for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of acetate buffer solution into the solution obtained in the step (c), and adjusting the pH value to 4.0;

(e) adding sodium chloride into the solution obtained in the step (d) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing and capping.

Example 10

1) Prescription

2) Preparation process

(a) Preparing an acetate buffer solution with the pH value of 3.5, and measuring the buffer solution with the prescription amount for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of phthalate buffer solution into the solution obtained in the step (c), and adjusting the pH value to 4.0;

(e) adding sodium chloride into the solution obtained in the step (d) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing and capping.

Comparative example 1

1) Prescription

2) Preparation process

Precisely measuring a citric acid-sodium citrate buffer solution with the pH value of 3.8, adding a proper amount of water for injection, and uniformly mixing; adding sodium chloride, stirring or shaking to dissolve completely; adding rocuronium bromide, stirring or shaking to completely dissolve, and adjusting pH to 4.0 with 1mol/L citric acid or 1mol/L sodium hydroxide; then adding 0.05% (w/v) of active carbon for injection, stirring for 30min at room temperature, and coarsely filtering; quantifying, filtering and sterilizing by a 0.22 mu m microporous filter membrane; filling, wherein each bottle is 2.5ml or 5ml, pressing a rubber plug completely, and rolling a cover; sterilizing at 121 deg.C under hot pressure for 20 min; and (5) inspecting, printing, packaging and storing in a refrigerator at 2-8 ℃.

Comparative example 2

1) Prescription

2) The preparation method comprises the following steps:

(a) taking sorbitol, methionine and ammonium acetate according to the prescription amount, adding water for injection, stirring for dissolving, then adding 3g of active carbon for injection, stirring for adsorbing for 30min, decarburizing and filtering to obtain filtrate;

(b) heating the filtrate to 87 ℃, preserving the heat for 10min, adding 10g rocuronium bromide, stirring for dissolving, adding glacial acetic acid to ensure that the pH value is 6.3, and uniformly stirring;

(c) filtering with microporous membrane with average pore diameter of 0.22 μm, filling nitrogen into the medicinal liquid, bottling in brown ampoule, sterilizing in 121 deg.C water bath for 15min, testing with lamp, packaging, and storing.

Comparative example 3

1) Prescription

2) The preparation method comprises the following steps:

(a) taking povidone, adding water for injection, dissolving completely, adding 2/3 wt% of L-aspartic acid, dissolving completely, filtering with 0.22 μm filter element, and filtering to obtain filtrate;

(b) adding rocuronium bromide raw material into the standby filtrate, completely dissolving, adding the residual L-aspartic acid, and adding water for injection to 5000ml to obtain a solution;

(c) filtering the solution in step b with 0.22 μm filter core, bottling, and sterilizing at 121 deg.C for 30min to obtain 1000 injection.

Comparative example 4

1) Prescription

2) The preparation method comprises the following steps:

measuring 850g of water for injection cooled to below 25 ℃, aerating with nitrogen, cooling the solution to 8-12 ℃, adjusting the pH to 2.9-3.1 with glacial acetic acid to obtain a solution A, adding rocuronium bromide in the solution A in the formula amount, stirring and dissolving to obtain a solution B, adding sodium acetate and sodium chloride in the formula amount into the solution B, adjusting the pH of the solution B to 2.9-3.1 with glacial acetic acid, supplementing 1000.0g of water for injection, adjusting the pH of the solution B to 3.9-4.1 with glacial acetic acid or sodium hydroxide to obtain a solution C, and stopping nitrogen aeration; and (3) passing the solution C through a polyvinylidene fluoride membrane with the diameter of 0.2 mu m, and filling 5 ml.

Comparative example 5

1) Prescription

2) Preparation process

(a) Preparing a lysine-hydrochloric acid buffer solution with the pH value of 3.0, and measuring the buffer solution with the amount according to the prescription for standby;

(b) adding polyethylene glycol 1000 into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of phosphate buffer solution into the solution obtained in the step (c), and adjusting the pH value to 4.5;

(e) adding sodium chloride into the solution obtained in the step (d) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing and capping.

Comparative example 6

1) Prescription

2) Preparation process

(a) Preparing a glycine-hydrochloric acid buffer solution with the pH value of 3.5, measuring the buffer solution with the prescription amount, and uniformly mixing for later use;

(b) adding rocuronium bromide into the buffer solution obtained in the step (a), and stirring for dissolving;

(c) adding a proper amount of succinate buffer solution into the solution obtained in the step (b), and adjusting the pH value to 4.0;

(d) adding sodium chloride into the solution obtained in the step (c) to adjust the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(e) quantifying, sterilizing, filtering, filling, pressing, and capping.

Verification examples

1. Long term stability test

To further prove the superiority of the present invention, the inventors conducted long-term stability experiments on the products obtained in the examples of the present invention and comparative examples.

The rocuronium bromide injection solutions prepared in examples 1-10 of the present invention and comparative examples 1-6 were stored at 25 ℃ ± 2 ℃ and 60% RH ± 5% RH for one year, and the related substances of the examined samples were measured at 0 month, 3 months, 6 months, 9 months, and 12 months, respectively, and the specific data are shown in the following table:

TABLE 1 Long-term stability test results

2. Accelerated test

The rocuronium bromide injection prepared in the examples 1-10 of the present invention and the comparative examples 1-6 was placed in a constant temperature and humidity chamber with 40 ℃. + -. 2 ℃ and 75%. + -. 5% relative humidity for 6 months, and samples were periodically taken at 0, 1, 2, 3, and 6 months to measure the contents of the related substances, and the results of the measurements are shown in the following table.

TABLE 2 stability results of accelerated testing

In the examples 1 to 10 of the invention, the content of the impurity C is only 2.36% at most in the accelerated test of 6 months, the polyethylene glycol 1000 vitamin E succinate is not added in the comparative example 6, and the content of the impurity C reaches 3.68% in the accelerated test of 6 months, which shows that the stability of the rocuronium bromide injection can be remarkably improved by selecting the polyethylene glycol 1000 vitamin E succinate as the stabilizer. Example 7 is a buffer system, and after the formula of example 10 is changed, the prepared injection solutions have poor stability compared with examples 1-6, which shows that the double buffer system of buffer solution and pH regulator can improve the stability of rocuronium bromide to a certain extent.

Claims (7)

1. The steroid muscle relaxant injection is characterized by comprising rocuronium bromide, a buffer solution, a pH regulator, an osmotic pressure regulator and polyethylene glycol 1000 vitamin E succinate, wherein the buffer solution is an amino acid-hydrochloric acid buffer solution; the pH regulator is one of acetate buffer solution, citrate buffer solution, mesylate buffer solution, tartrate buffer solution and succinate buffer solution; the pH value of the steroid muscle relaxant injection is 3.5-5.0.

2. The steroid muscle relaxant injection according to claim 1, wherein the buffer is one of glycine-hydrochloric acid and alanine-hydrochloric acid.

3. The steroid muscle relaxant injection according to claim 1, wherein the pH adjuster is one of a tartrate buffer and a succinate buffer.

4. The steroid muscle relaxant injection according to claim 1, wherein the osmolality adjusting agent is sodium chloride.

5. The steroid muscle relaxant injection according to claim 1, comprising the following specific components:

。

6. a method for preparing the steroid muscle relaxant injection according to any one of claims 1 to 5, comprising the steps of:

(a) preparing a buffer solution with a certain pH value, and measuring the buffer solution with a prescribed amount for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of pH regulator into the solution obtained in the step (c) to regulate the pH value;

(e) adding an osmotic pressure regulator into the solution obtained in the step (d) to regulate the osmotic pressure, and stirring for dissolving;

(f) quantifying, sterilizing, filtering and filling.

7. The method of claim 6, further comprising the steps of:

(a) preparing a buffer solution with the pH value of 3.0-4.0, and measuring the buffer solution with the amount according to the prescription for later use;

(b) adding polyethylene glycol 1000 vitamin E succinate into the buffer solution in the step (a), and stirring until the solution is clear;

(c) adding rocuronium bromide into the solution obtained in the step (b), and stirring for dissolving;

(d) adding a proper amount of pH regulator into the solution obtained in the step (c), and regulating the pH value to 3.5-5.0;

(e) adding an osmotic pressure regulator into the solution obtained in the step (d) to regulate the osmotic pressure to be 285-320 mOsmol/kg, and stirring for dissolving;

(f) quantifying, sterilizing, filtering, filling, pressing and capping.