阅读说明：本技术 一种注射用甲泼尼龙琥珀酸钠冻干粉针剂及其制备方法 (Methylprednisolone sodium succinate freeze-dried powder injection for injection and preparation method thereof ) 是由 李海 杨亚勇 智红英 刘世普 白腾飞 于 2021-07-20 设计创作，主要内容包括：本发明涉及一种注射用甲泼尼龙琥珀酸钠冻干粉针剂及其制备方法,属于药物制剂领域,所述冻干粉针剂规格为40mg时,包括甲泼尼龙琥珀酸钠、pH缓冲剂和稳定剂,制备方法为向磷酸氢二钠-柠檬酸缓冲液加入稳定剂,搅拌溶清加入甲泼尼龙琥珀酸钠,定容并摇匀,得到配制液,将配制液均匀分装至西林瓶后冻干得到产品；规格≥125mg时,包括甲泼尼龙琥珀酸钠和pH缓冲剂,制备方法不添加稳定剂。本发明制备的注射用甲泼尼龙琥珀酸钠冻干粉针剂质量好,稳定性高,储存过程降解率低；所得产品用5%葡萄糖注射液复溶时间短。(The invention relates to a methylprednisolone sodium succinate freeze-dried powder injection for injection and a preparation method thereof, belonging to the field of pharmaceutical preparations, wherein the lyophilized powder injection comprises methylprednisolone sodium succinate, a pH buffering agent and a stabilizing agent when the specification is 40mg, and the preparation method comprises the steps of adding the stabilizing agent into a disodium hydrogen phosphate-citric acid buffer solution, adding the methylprednisolone sodium succinate into a stirring solution, fixing the volume and shaking up to obtain a preparation solution, uniformly subpackaging the preparation solution into penicillin bottles, and freeze-drying to obtain a product; when the specification is more than or equal to 125mg, the methylprednisolone sodium succinate and the pH buffering agent are included, and the preparation method does not add a stabilizing agent. The methylprednisolone sodium succinate freeze-dried powder injection for injection prepared by the invention has good quality, high stability and low degradation rate in the storage process; the obtained product has short redissolution time by using 5% glucose injection.)

1. A methylprednisolone sodium succinate freeze-dried powder injection for injection is characterized in that: when the specification is 40mg, the composition comprises methylprednisolone sodium succinate, a pH buffering agent and a stabilizing agent; when the specification is more than or equal to 125mg, the composition comprises methylprednisolone sodium succinate and a pH buffering agent.

2. The methylprednisolone sodium succinate freeze-dried powder injection for injection as claimed in claim 1, wherein: the pH buffering agent comprises disodium hydrogen phosphate and citric acid; the stabilizer is sucrose and/or lactose.

3. The methylprednisolone sodium succinate freeze-dried powder injection for injection as claimed in claim 2, wherein: when the specification is 40mg, the formula of each freeze-dried powder injection is as follows: 53.0mg of methylprednisolone sodium succinate, 25mg of stabilizer, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid; when the specification is more than or equal to 125mg, the formula of each freeze-dried powder injection is as follows: 165.7-1326.0 mg of methylprednisolone sodium succinate, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid.

4. A method for preparing the methylprednisolone sodium succinate freeze-dried powder injection for injection as defined in any one of claims 1-3, which is characterized in that: the method comprises the following steps:

(1) preparing a disodium hydrogen phosphate-citric acid buffer solution for later use;

(2) when the specification is 40mg, adding a stabilizer into the buffer solution in the step (1), and stirring and dissolving for later use;

(3) adding methylprednisolone sodium succinate into the solution in the step (1) or the step (2), stirring until the solution is clear, adding water for injection to a constant volume, and shaking up to obtain a preparation solution;

(4) uniformly subpackaging the prepared solution obtained in the step (3) into penicillin bottles, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(5) and (5) freeze-drying the sample to be freeze-dried obtained in the step (4), capping and packaging to obtain a finished product.

5. The method for preparing the methylprednisolone sodium succinate freeze-dried powder injection for injection according to claim 4, which is characterized in that: the freeze-drying process in the step (5) is that the temperature of a freeze dryer is reduced from room temperature to-35 ℃ to-50 ℃, then a sample to be freeze-dried is placed in the freeze dryer, and the temperature is kept for 2-4 hours; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

6. The method for preparing the methylprednisolone sodium succinate freeze-dried powder injection for injection according to claim 4, which is characterized in that: the pH value of the buffer solution in the step (1) is 6.0-8.0.

Technical Field

The invention relates to a methylprednisolone sodium succinate freeze-dried powder injection for injection and a preparation method thereof, belonging to the field of pharmaceutical preparations.

Background

Methylprednisolone is a middle-effect glucocorticoid medicine and has pharmacological actions of resisting inflammation, immunosuppression, antianaphylaxis, antishock and the like. The medicine has strong anti-inflammatory effect and weak water and sodium retention, and is widely applied clinically. The methylprednisolone sodium succinate is a water-soluble methylprednisolone derivative (prodrug), and the high-concentration aqueous solution is particularly suitable for treating diseases needing hormone treatment with strong action and quick response, but needs to be prepared into powder injection because the methylprednisolone sodium succinate is not stable in the aqueous solution and cannot be stored for a long time.

At present, methylprednisolone sodium succinate freeze-dried powder injection mostly takes methylprednisolone succinate as a raw material, methylprednisolone sodium succinate is generated through reaction in preparation, water-insoluble methylprednisolone is easily generated in the preparation and storage processes, the clarity after redissolution is influenced, the stability is poor, and compared with the original ground (American glimmer) product, the redissolution time of 5% glucose injection is longer, and the use of medical care personnel is influenced; in addition, studies have shown that long reconstitution times may lead to a lag in clinical efficacy or even ineffectiveness. Therefore, the product stability of the methylprednisolone sodium succinate freeze-dried powder injection for injection is improved, and the redissolution time of 5% glucose injection is shortened, so that the methylprednisolone sodium succinate freeze-dried powder injection has important clinical significance.

Disclosure of Invention

The invention aims to provide a methylprednisolone sodium succinate freeze-dried powder injection for injection and a preparation method thereof, and the obtained product has good stability and short redissolution time with 5% glucose injection.

In order to achieve the purpose, the invention adopts the technical scheme that:

a lyophilized powder for injection comprises methylprednisolone sodium succinate, pH buffer and stabilizer, when the specification is 40 mg; when the specification is more than or equal to 125mg, the composition comprises methylprednisolone sodium succinate and a pH buffering agent.

The technical scheme of the invention is further improved as follows: the pH buffering agent comprises disodium hydrogen phosphate and citric acid; the stabilizer is sucrose and/or lactose.

The technical scheme of the invention is further improved as follows: when the specification is 40mg, the formula of each freeze-dried powder injection is as follows: 53.0mg of methylprednisolone sodium succinate, 25mg of stabilizer, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid; when the specification is more than or equal to 125mg, the formula of each freeze-dried powder injection is as follows: 165.7-1326.0 mg of methylprednisolone sodium succinate, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid.

A method for preparing methylprednisolone sodium succinate freeze-dried powder injection for injection comprises the following steps:

(1) preparing a disodium hydrogen phosphate-citric acid buffer solution for later use;

(2) when the specification is 40mg, adding a stabilizer into the buffer solution in the step (1), and stirring and dissolving for later use;

(3) adding methylprednisolone sodium succinate into the solution in the step (1) or the step (2), stirring until the solution is clear, adding water for injection to a constant volume, and shaking up to obtain a preparation solution;

(4) uniformly subpackaging the prepared solution obtained in the step (3) into penicillin bottles, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(5) and (5) freeze-drying the sample to be freeze-dried obtained in the step (4), capping and packaging to obtain a finished product.

The technical scheme of the invention is further improved as follows: the freeze-drying process in the step (5) is that the temperature of a freeze dryer is reduced from room temperature to-35 ℃ to-50 ℃, then a sample to be freeze-dried is placed in the freeze dryer, and the temperature is kept for 2-4 hours; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

The technical scheme of the invention is further improved as follows: the pH value of the buffer solution in the step (1) is 6.0-8.0.

Due to the adoption of the technical scheme, the invention has the following technical effects:

the methylprednisolone sodium succinate freeze-dried powder injection for injection prepared by the invention has the advantages of good quality, high stability and low degradation rate in the storage process.

The methylprednisolone sodium succinate freeze-dried powder injection for injection prepared by the invention has good solubility, short redissolution time by using 5% glucose injection, and shortened drug dissolution time of medical personnel in the using process.

The preparation method has simple steps and simple conditions, and is beneficial to industrial production.

Detailed Description

The present invention will be described in further detail with reference to specific examples below:

a methylprednisolone sodium succinate lyophilized powder for injection, when the specification is 40mg, the formula of each lyophilized powder for injection is as follows: 53.0mg of methylprednisolone sodium succinate, 25mg of stabilizer, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid, wherein the stabilizer is cane sugar and/or lactose; when the specification is more than or equal to 125mg, the formula of each freeze-dried powder injection is as follows: 165.7-1326.0 mg of methylprednisolone sodium succinate, 18-27 mg of disodium hydrogen phosphate and 1-8 mg of citric acid.

A method for preparing methylprednisolone sodium succinate freeze-dried powder injection for injection comprises the following steps:

(1) preparing a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 6.0-8.0 for later use;

(2) when the specification is 40mg, adding a stabilizer into the buffer solution in the step (1), and stirring and dissolving for later use;

(3) adding methylprednisolone sodium succinate into the solution in the step (1) or the step (2), stirring until the solution is clear, adding water for injection to a constant volume, and shaking up to obtain a preparation solution;

(4) uniformly subpackaging the prepared solution obtained in the step (3) into penicillin bottles, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(5) cooling the temperature of a freeze dryer from room temperature to-35 to-50 ℃, then putting the sample to be freeze-dried obtained in the step (4), and keeping the temperature for 2-4 h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

Example 1

The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection comprises the following components: 53.0mg of methylprednisolone sodium succinate, 25mg of lactose, 23mg of disodium hydrogen phosphate and 4mg of citric acid.

The preparation method comprises the following steps of:

(1) weighing 2300mg of disodium hydrogen phosphate (anhydrous) and 400mg of citric acid, and adding 80ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH of 7.0 for later use;

(2) adding 2500mg of lactose into the buffer solution in the step (1), and stirring for dissolving for later use;

(3) adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;

(4) subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(5) cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (4), and keeping the temperature for 2-4 h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

Example 2

The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection comprises the following components: 53.0mg of methylprednisolone sodium succinate, 25mg of cane sugar, 23mg of disodium hydrogen phosphate and 4mg of citric acid.

The preparation method comprises the following steps of:

(1) weighing 2300mg of disodium hydrogen phosphate (anhydrous) and 400mg of citric acid, and adding 80ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH of 7.0 for later use;

(2) adding 2500mg of sucrose into the buffer solution in the step (1), and stirring and dissolving for later use;

(3) adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;

(4) subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(5) cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (4), and keeping the temperature for 2-4 h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

Example 3

The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection comprises the following components: 53.0mg of methylprednisolone sodium succinate, 12.5mg of lactose, 12.5mg of cane sugar, 23mg of disodium hydrogen phosphate and 4mg of citric acid.

The preparation method comprises the following steps of:

(1) weighing 2300mg of disodium hydrogen phosphate (anhydrous) and 400mg of citric acid, and adding 80ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH of 7.0 for later use;

(2) adding 1250mg of lactose and 1250mg of sucrose into the buffer solution in the step (1), and stirring and dissolving for later use;

(3) adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;

(4) subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(5) cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (4), and keeping the temperature for 2-4 h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

Example 4

The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection comprises the following components: 53.0mg of methylprednisolone sodium succinate, 12.5mg of lactose, 12.5mg of cane sugar, 18mg of disodium hydrogen phosphate and 8mg of citric acid.

The preparation method comprises the following steps of:

(1) weighing 1800mg of disodium hydrogen phosphate (anhydrous) and 800mg of citric acid, and adding 80ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 6.0 for later use;

(2) adding 1250mg of lactose and 1250mg of sucrose into the buffer solution in the step (1), and stirring and dissolving for later use;

(3) adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;

(4) subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(5) cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (4), and keeping the temperature for 2-4 h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

Example 5

The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection comprises the following components: 53.0mg of methylprednisolone sodium succinate, 12.5mg of lactose, 12.5mg of cane sugar, 27mg of disodium hydrogen phosphate and 1mg of citric acid.

The preparation method comprises the following steps of:

(1) weighing 2700mg of disodium hydrogen phosphate (anhydrous) and 100mg of citric acid, and adding 80ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 7.8 for later use;

(2) adding 1250mg of lactose and 1250mg of sucrose into the buffer solution in the step (1), and stirring and dissolving for later use;

(3) adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;

(4) subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(5) cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (4), and keeping the temperature for 2-4 h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

Example 6

The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 125mg, and the formula of each freeze-dried powder injection comprises the following components: 165.7mg of methylprednisolone sodium succinate, 23mg of disodium hydrogen phosphate and 4mg of citric acid.

The preparation method comprises the following steps of:

(1) weighing 2300mg of disodium hydrogen phosphate (anhydrous) and 400mg of citric acid, and adding 160ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 7.0 for later use;

(2) adding 16.57g of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to a constant volume of 200ml, and shaking up to obtain a preparation solution;

(3) subpackaging the prepared solution obtained in the step (2) into penicillin bottles according to the standard of 2 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(4) cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (3), and keeping the temperature for 2-4 h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

Example 7

The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 500mg, and the formula of each freeze-dried powder injection comprises the following components: 663.0mg of methylprednisolone sodium succinate, 18mg of disodium hydrogen phosphate and 8mg of citric acid.

The preparation method comprises the following steps of:

(1) weighing 1800mg of disodium hydrogen phosphate (anhydrous) and 800mg of citric acid, and adding 640ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH value of 6.0 for later use;

(2) adding 66.30g of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 800ml, and shaking up to obtain a preparation solution;

(3) subpackaging the prepared solution obtained in the step (2) into penicillin bottles according to the standard of 8 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(4) cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (3), and keeping the temperature for 2-4 h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

Example 8

The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 1000mg, and the formula of each freeze-dried powder injection comprises the following components: 1326.0mg of methylprednisolone sodium succinate, 27mg of disodium hydrogen phosphate and 1mg of citric acid.

The preparation method comprises the following steps of:

(1) weighing 2700mg of disodium hydrogen phosphate (anhydrous) and 100mg of citric acid, and adding 1280ml of water for injection to prepare a disodium hydrogen phosphate-citric acid buffer solution with the pH of 7.8 for later use;

(2) adding 132.60g of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to a constant volume of 1600ml, and shaking up to obtain a preparation solution;

(3) subpackaging the prepared solution obtained in the step (2) into penicillin bottles according to the standard of 16 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(4) cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (3), and keeping the temperature for 2-4 h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

Comparative example 1

The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 40mg, and the formula of each freeze-dried powder injection comprises the following components: 53.0mg of methylprednisolone sodium succinate, 25mg of lactose, 17.46mg of disodium hydrogen phosphate and 1.6mg of sodium dihydrogen phosphate monohydrate.

The preparation method comprises the following steps of:

(1) 1746mg of disodium hydrogen phosphate (anhydrous) and 160mg of sodium dihydrogen phosphate monohydrate are weighed, and 80ml of water for injection is added to prepare a disodium hydrogen phosphate-sodium dihydrogen phosphate buffer solution with the pH value of 7.0 for later use;

(2) adding 2500mg of lactose into the buffer solution in the step (1), and stirring for dissolving for later use;

(3) adding 5300mg of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to fix the volume to 100ml, and shaking up to obtain a preparation solution;

(4) subpackaging the prepared solution obtained in the step (3) into penicillin bottles according to the standard of 1 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(5) cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (4), and keeping the temperature for 2-4 h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

Comparative example 2

The specification of the methylprednisolone sodium succinate freeze-dried powder injection for injection is 125mg, and the formula of each freeze-dried powder injection comprises the following components: 165.7mg of methylprednisolone sodium succinate, 17.46mg of disodium hydrogen phosphate and 1.6mg of sodium dihydrogen phosphate monohydrate.

The preparation method comprises the following steps of:

(1) 1746mg of disodium hydrogen phosphate (anhydrous) and 160mg of sodium dihydrogen phosphate monohydrate are weighed, and 160ml of water for injection is added to prepare a disodium hydrogen phosphate-sodium dihydrogen phosphate buffer solution with the pH value of 7.0 for later use;

(2) adding 16.57g of methylprednisolone sodium succinate into the solution in the step (2), stirring until the solution is clear, adding water for injection to a constant volume of 200ml, and shaking up to obtain a preparation solution;

(3) subpackaging the prepared solution obtained in the step (2) into penicillin bottles according to the standard of 2 ml/bottle, and semi-pressing rubber plugs to obtain samples to be lyophilized;

(4) cooling the freeze dryer from room temperature to-35-50 ℃, then putting the sample to be freeze-dried obtained in the step (3), and keeping the temperature for 2-4 h; then heating to-10-20 ℃, controlling the vacuum degree at 0.1-0.3 mbar, and preserving heat for 6-15 h; and finally, heating to 30-40 ℃, controlling the vacuum degree to be 0.1-0.3 mbar, and preserving heat for 2-4 hours.

Comparative example 3

125mg of methylprednisolone sodium succinate freeze-dried powder injection for injection is prepared according to example 1 in patent CN 104434820A.

Table 1 shows the product stability comparison results of examples and comparative examples:

TABLE 1

Note: a-illumination for 10 days, B-60 ℃ for 10 days.

As can be seen from table 1 above: compared with the products of the comparative example and the products sold on the market, the products of the examples have high stability, and the growth rate of free methylprednisolone and total impurities is low; especially, the stability of the product is best when the pH of the product is 7.8.

Table 2 shows the comparative results of the products of the examples and the control examples reconstituted with 5% glucose injection:

TABLE 2

As can be seen from table 2 above: the 5% glucose injection of the product of the example has a remarkably shortened re-dissolving time trend, which is obviously shorter than that of the original product (pfeiri).