A cefminox sodium preparation for injection and a method for preparing the same
By combining sodium lactate Ringer's solution, vitamin B12 injection, and modified composite antioxidants, the degradation problem of cefminox sodium under photothermal action was solved, and the stability and safety of injectable cefminox sodium preparations in specific environments were achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- 上海欣峰制药有限公司
- Filing Date
- 2024-01-25
- Publication Date
- 2026-07-07
AI Technical Summary
Cefminox sodium is easily degraded under the influence of light and heat, resulting in a decrease in the content of the active ingredient and affecting the safety and reliability of medication.
A cefminox sodium formulation for injection was prepared by combining sodium lactate Ringer's solution, vitamin B12 injection, and a modified composite antioxidant with cefminox sodium through ultrasonic oscillation and stirring, thereby enhancing its stability under light and heat.
Cefminox sodium exhibits excellent stability and its content remains stable under conditions of 35℃±2℃, 65%±5%RH, and natural light exposure, ensuring the safety and reliability of medication.
Smart Images
Figure CN117899014B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to an injectable cefminox sodium formulation and its preparation method. Background Technology
[0002] Cefminox sodium is (6R,7S)-7-[(S)-2-[2-amino-2-hydroxyethyl mercapto]-acetamido]-7-methoxy-3-[[(1-methyl-1H-tetrazol-5-yl)-mercapto]-methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate sodium salt heptahydrate, with a molecular weight of 667.66 Daltons.
[0003] Cefminox sodium is a cephalosporin antibiotic, and its action is similar to that of third-generation cephalosporins. Clinically, cefminox sodium is administered intravenously. Cefminox sodium has broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria, particularly against *Escherichia coli*, *Klebsiella* spp., *Haemophilus influenzae*, *Proteus* spp., and *Bacteroides fragilis*. Its mechanism of action involves a strong affinity for penicillin-binding proteins, the usual target site of β-lactam antibiotics, inhibiting cell wall synthesis and binding to peptidoglycan. This inhibits the binding of peptidoglycan to lipoproteins, promoting lysis and resulting in strong bactericidal activity within a short time.
[0004] Like other cephalosporins, cefminox sodium is sensitive to environmental factors and is prone to degradation, oxidation, or polymerization under the influence of light and heat. Prolonged exposure can lead to the formation of impurities, resulting in a decrease in the content of the active ingredient (cefminox sodium), which in turn affects its safety and reliability. Summary of the Invention
[0005] To address the problems existing in the background art, the present invention provides an injectable cefminox sodium preparation and its preparation method. When the preparation is exposed to an environment of 35℃±2℃, 65%±5%RH and natural light, the cefminox sodium exhibits excellent stability and the content remains stable, thus ensuring the safety and reliability of medication.
[0006] To achieve the above objectives, the present invention provides the following technical solution:
[0007] A cefminox sodium injection formulation, by weight, comprises the following components: 1 part of refined cefminox sodium, 0.5 parts of sodium lactate Ringer's solution, 0.2 parts of vitamin B12 injection, 0.1-0.3 parts of modified composite antioxidant, and 3 parts of physiological saline.
[0008] The preparation method of the modified composite antioxidant is as follows:
[0009] S1. Add 1 part by weight of poloxamer to 20 parts by weight of distilled water and stir for 6-8 minutes to obtain a solution;
[0010] S2. Pass 1 part by weight of natural vitamin C through a 100-mesh sieve and mix it into the solution obtained in S1. Then, sonicate for 10-15 minutes to obtain a vitamin C solution.
[0011] S3. Mix 0.5 parts by weight of vitamin D into the vitamin C solution obtained in S2, and sonicate for 15-20 minutes to obtain the modified composite antioxidant.
[0012] Furthermore, by weight, it includes the following components: 1 part of cefminox sodium concentrate, 0.5 parts of sodium lactate Ringer's solution, 0.2 parts of vitamin B12 injection, 0.15 parts of modified compound antioxidant, and 3 parts of physiological saline.
[0013] Furthermore, the preparation method of the cefminox sodium concentrate is as follows:
[0014] A1. Weigh 24g of crude cefminox sodium and put it into a beaker containing 250mL of deionized water. Stir for 20min to ensure complete dissolution and obtain a solution.
[0015] A2. Weigh 0.24g of activated carbon and add it to the solution obtained in A1. Stir for 25 minutes, filter, and obtain the filtrate.
[0016] A3. Transfer the filtrate into the crystallizer, turn on the stirrer, turn on the peristaltic pump, and pump 120 mL of ethanol into the crystallizer at a dropping rate of 6 mL / min. Turn off the peristaltic pump, weigh 2.4 g of seed crystals and add them into the crystallizer, continue stirring for 18 min, then stop stirring and grow the crystals for 85 min to obtain the crystal growth solution.
[0017] A4. Turn on the peristaltic pump and pump 120 mL of ethanol into the crystal growth solution obtained in A3. Filter by suction, wash with acetone, collect the crystal product, and vacuum dry at 42°C for two hours to obtain the high-quality cefminox sodium.
[0018] Furthermore, the stirring speed is 300 r / min.
[0019] Furthermore, in S2, the frequency of ultrasonic oscillation is 80-100 kHz.
[0020] Furthermore, in S3, the frequency of ultrasonic oscillation is 100-120 kHz.
[0021] Furthermore, the saline solution is a 0.9% sodium chloride solution.
[0022] A method for preparing an injectable cefminox sodium formulation, used to prepare the injectable cefminox sodium formulation as described in any one of claims 1-7, comprising the following steps: first, mixing sodium lactate Ringer's solution, vitamin B12 injection, modified composite antioxidant and physiological saline, then adding cefminox sodium concentrate, mixing evenly to obtain the injectable cefminox sodium formulation; in specific use, the injectable cefminox sodium formulation is diluted with physiological saline.
[0023] This application has the following beneficial effects:
[0024] 1. Sodium lactate Ringer's solution can balance the acid-base balance in the formulation system; Vitamin B12 injection itself has light absorption capacity, which can improve the stability of the formulation components in the light environment; The modified compound antioxidant has excellent antioxidant performance, which is better than the effect of individual oxidants or the simple mixture of multiple oxidants; The three work synergistically, and their effects promote each other, which can better improve the stability of cefminox sodium content in the formulation. This ensures that when the formulation is exposed to natural light at 35℃±2℃, 65%±5%RH, cefminox sodium exhibits excellent stability and the content remains stable, thus guaranteeing the safety and reliability of medication.
[0025] 2. First, dissolve water-soluble natural vitamin C powder in a diluted aqueous solution of poloxamer, and then dissolve fat-soluble vitamin D. Both dissolution processes are performed using ultrasonic vibration, with the frequency and duration of the ultrasonic vibration increasing in the latter process compared to the former, in order to obtain a high-performance modified composite antioxidant. During the preparation process, changes in stirring conditions or the removal or replacement of any raw material will lead to a decrease in the performance of the modified composite antioxidant in maintaining the stability of cefminox sodium in the formulation. Attached Figure Description
[0026] Figure 1 This is a graph showing the change trend of the relative content of cefminox sodium in the formulations of Examples 1-5 and Comparative Examples 1-5 of the present invention as the storage time increases;
[0027] Figure 2 This is a graph showing the change trend of the relative content of cefminox sodium in the formulations of Examples 1-5 and Comparative Examples 4, 6 and 7 of the present invention as the storage time increases;
[0028] Figure 3 The graph shows the trend of the relative content of cefminox sodium in the formulations of Examples 1-5 and Comparative Examples 8-12 of this invention as the storage time increases. Detailed Implementation
[0029] The present application will be further described in detail below with reference to the embodiments.
[0030] Unless otherwise specified, the raw materials used in the embodiments and comparative examples of this application are all commercially available. Example 1
[0031] I. The preparation steps of the modified composite antioxidant are as follows:
[0032] S1. Add 10g of poloxamer to 200g of distilled water and stir for 7 minutes to obtain a solution;
[0033] S2. Pass 10g of natural vitamin C through a 100-mesh sieve and mix it into the solution obtained in S1. Then, sonicate for 12 minutes at a frequency of 90KHZ to obtain a vitamin C solution.
[0034] S3. Mix 5g of vitamin D into the vitamin C solution obtained in S2, and sonicate for 18 minutes at a frequency of 110KHZ to obtain 225g of modified composite antioxidant.
[0035] II. The preparation steps of the high-quality cefminox sodium are as follows:
[0036] A1. Weigh 24g of crude cefminox sodium and put it into a beaker containing 250mL of deionized water. Stir for 20min at a speed of 300r / min to ensure complete dissolution and obtain a solution.
[0037] A2. Weigh 0.24g of activated carbon and add it to the solution obtained in A1. Stir for 25 minutes, filter, and obtain the filtrate.
[0038] A3. Transfer the filtrate into the crystallizer, turn on the stirrer, turn on the peristaltic pump, and pump 120 mL of ethanol into the crystallizer at a dropping rate of 6 mL / min. Turn off the peristaltic pump, weigh 2.4 g of seed crystals and add them to the crystallizer, continue stirring for 18 min at a stirring speed of 300 r / min, then stop stirring and grow the crystals for 85 min to obtain the crystal growth solution.
[0039] A4. Turn on the peristaltic pump and pump 120 mL of ethanol into the crystal growth solution obtained in A3. Filter by suction, wash with acetone, collect the crystal product, and vacuum dry at 42°C for two hours to obtain the high-quality cefminox sodium.
[0040] The preparation steps for cefminox sodium for injection are as follows:
[0041] First, mix 0.5g of sodium lactate Ringer's solution, 0.2g of vitamin B12 injection, 0.1g of modified compound antioxidant and 3g of physiological saline (0.9% sodium chloride solution). Then add 1g of cefminox sodium concentrate and mix well to obtain cefminox sodium preparation for injection.
[0042] When administering the injection, dilute the cefminox sodium preparation with physiological saline (0.9% sodium chloride solution) first, depending on the actual situation, before use. Example 2
[0043] In this embodiment, the preparation steps of the modified composite antioxidant and the preparation steps of the cefminox sodium concentrate are the same as in Example 1.
[0044] The only difference between this embodiment and Embodiment 1 is that:
[0045] The preparation steps of cefminox sodium for injection are as follows: First, mix 0.5g of sodium lactate Ringer's solution, 0.2g of vitamin B12 injection, 0.15g of modified composite antioxidant and 3g of physiological saline (0.9% sodium chloride solution), then add 1g of cefminox sodium concentrate and mix evenly to obtain cefminox sodium for injection. Example 3
[0046] In this embodiment, the preparation steps of the modified composite antioxidant and the preparation steps of the cefminox sodium concentrate are the same as in Example 1.
[0047] The only difference between this embodiment and Embodiment 1 is that:
[0048] The preparation steps of cefminox sodium for injection are as follows: First, mix 0.5g of sodium lactate Ringer's solution, 0.2g of vitamin B12 injection, 0.2g of modified composite antioxidant and 3g of physiological saline (0.9% sodium chloride solution), then add 1g of cefminox sodium concentrate and mix evenly to obtain cefminox sodium for injection. Example 4
[0049] In this embodiment, the preparation steps of the modified composite antioxidant and the preparation steps of the cefminox sodium concentrate are the same as in Example 1.
[0050] The only difference between this embodiment and Embodiment 1 is that:
[0051] The preparation steps of cefminox sodium for injection are as follows: First, mix 0.5g of sodium lactate Ringer's solution, 0.2g of vitamin B12 injection, 0.25g of modified composite antioxidant and 3g of physiological saline (0.9% sodium chloride solution), then add 1g of cefminox sodium concentrate and mix evenly to obtain cefminox sodium for injection. Example 5
[0052] In this embodiment, the preparation steps of the modified composite antioxidant and the preparation steps of the cefminox sodium concentrate are the same as in Example 1.
[0053] The only difference between this embodiment and Embodiment 1 is that:
[0054] The preparation steps of cefminox sodium for injection are as follows: First, mix 0.5g of sodium lactate Ringer's solution, 0.2g of vitamin B12 injection, 0.3g of modified composite antioxidant and 3g of physiological saline (0.9% sodium chloride solution), then add 1g of cefminox sodium concentrate and mix evenly to obtain cefminox sodium for injection. Comparative Example 1
[0055] In this comparative example, the preparation steps of the modified composite antioxidant and the preparation steps of the cefminox sodium concentrate are the same as in Example 1.
[0056] The only difference between this comparative example and Example 1 is that the raw materials for preparing the injectable cefminox sodium formulation do not include sodium lactate Ringer's. Comparative Example 2
[0057] In this comparative example, the preparation steps of the modified composite antioxidant and the preparation steps of the cefminox sodium concentrate are the same as in Example 1.
[0058] The only difference between this comparative example and Example 1 is that the raw materials for preparing the cefminox sodium injection do not include vitamin B12 injection. Comparative Example 3
[0059] In this comparative example, the preparation steps of the modified composite antioxidant and the preparation steps of the cefminox sodium concentrate are the same as in Example 1.
[0060] The only difference between this comparative example and Example 1 is that the raw materials for preparing the cefminox sodium injection do not include sodium lactate Ringer's solution and vitamin B12 injection. Comparative Example 4
[0061] In this comparative example, the preparation steps of the modified composite antioxidant and the preparation steps of the cefminox sodium concentrate are the same as in Example 1.
[0062] The only difference between this comparative example and Example 1 is that the raw materials for preparing the injectable cefminox sodium formulation do not include modified composite antioxidants. Comparative Example 5
[0063] In this comparative example, the preparation steps of the modified composite antioxidant and the preparation steps of the cefminox sodium concentrate are the same as in Example 1.
[0064] The only difference between this comparative example and Example 1 is that the raw materials for preparing the cefminox sodium injection do not include sodium lactate Ringer's solution, vitamin B12 injection, and modified composite antioxidant. Comparative Example 6
[0065] In this embodiment, the preparation steps of the modified composite antioxidant and the preparation steps of the cefminox sodium concentrate are the same as in Example 1.
[0066] The only difference between this embodiment and Embodiment 1 is that:
[0067] The preparation steps of cefminox sodium for injection are as follows: First, mix 0.5g of sodium lactate Ringer's solution, 0.2g of vitamin B12 injection, 0.05g of modified composite antioxidant and 3g of physiological saline (0.9% sodium chloride solution), then add 1g of cefminox sodium concentrate and mix evenly to obtain cefminox sodium for injection. Comparative Example 7
[0068] In this embodiment, the preparation steps of the modified composite antioxidant and the preparation steps of the cefminox sodium concentrate are the same as in Example 1.
[0069] The only difference between this embodiment and Embodiment 1 is that:
[0070] The preparation steps of cefminox sodium for injection are as follows: First, mix 0.5g of sodium lactate Ringer's solution, 0.2g of vitamin B12 injection, 0.35g of modified composite antioxidant and 3g of physiological saline (0.9% sodium chloride solution), then add 1g of cefminox sodium concentrate and mix evenly to obtain cefminox sodium for injection. Comparative Example 8
[0071] In this embodiment, the preparation steps of the high-quality cefminox sodium and the preparation steps of the injectable cefminox sodium formulation are the same as in Example 1.
[0072] The only difference between this embodiment and Example 1 is that in the preparation steps of the modified composite antioxidant, both ultrasonic oscillations are replaced with mechanical stirring at 250 r / min. Comparative Example 9
[0073] In this embodiment, the preparation steps of the high-quality cefminox sodium and the preparation steps of the injectable cefminox sodium formulation are the same as in Example 1.
[0074] The only difference between this embodiment and Example 1 is that the preparation steps of the modified composite antioxidant are as follows:
[0075] S1. Add 10g of poloxamer to 200g of distilled water and stir for 7 minutes to obtain a solution;
[0076] S2. Pass 15g of natural vitamin C through a 100-mesh sieve and mix it into the solution obtained in S1. Then, sonicate it for 12 minutes at a frequency of 90KHZ to obtain a vitamin C solution, which is 225g of modified composite antioxidant. Comparative Example 10
[0077] In this embodiment, the preparation steps of the high-quality cefminox sodium and the preparation steps of the injectable cefminox sodium formulation are the same as in Example 1.
[0078] The only difference between this embodiment and Example 1 is that the preparation steps of the modified composite antioxidant are as follows:
[0079] S1. Add 10g of poloxamer to 200g of distilled water and stir for 7 minutes to obtain a solution;
[0080] S2. Mix 15g of natural vitamin D into the solution obtained in S1, and sonicate for 18 minutes at a frequency of 120KHZ to obtain a vitamin D solution, which is 225g of modified composite antioxidant. Comparative Example 11
[0081] In this embodiment, the preparation steps of the high-quality cefminox sodium and the preparation steps of the injectable cefminox sodium formulation are the same as in Example 1.
[0082] The only difference between this embodiment and Example 1 is that the preparation steps of the modified composite antioxidant are as follows:
[0083] S1. Pass 10g of natural vitamin C through a 100-mesh sieve, mix it into 210g of distilled water, and sonicate for 12 minutes at a frequency of 90KHZ to obtain a vitamin C solution.
[0084] S3. Mix 5g of vitamin D into the vitamin C solution obtained in S2, and sonicate for 18 minutes at a frequency of 110KHZ to obtain 225g of modified composite antioxidant. Comparative Example 12
[0085] In this embodiment, the preparation steps of the high-quality cefminox sodium and the preparation steps of the injectable cefminox sodium formulation are the same as in Example 1.
[0086] The only difference between this embodiment and Example 1 is that the preparation steps of the modified composite antioxidant are as follows:
[0087] S1. Add 10g of phospholipid to 200g of distilled water, heat and stir for 7 minutes to obtain a solution;
[0088] S2. Pass 10g of natural vitamin C through a 100-mesh sieve and mix it into the solution obtained in S1. Then, sonicate for 12 minutes at a frequency of 90KHZ to obtain a vitamin C solution.
[0089] S3. Mix 5g of vitamin D into the vitamin C solution obtained in S2, and sonicate for 18 minutes at a frequency of 110KHZ to obtain 225g of modified composite antioxidant.
[0090] Experimental Example 1
[0091] Test item: Allergy test.
[0092] Experimental method: Forty-two white mice were randomly divided into seven groups: five groups of cefminox sodium preparation for injection (15 mg / mL) as described in Examples 1-5, an ovalbumin solution positive group (15 mg / mL), and a saline control group, with six mice in each group. Each group was injected intraperitoneally with 0.5 mL of the corresponding fluid every other day for a total of three times.
[0093] The animals in each group were then divided into two groups of three. One group was challenged 14 days after the first administration by injecting 2 mL of the corresponding solution into the marginal ear vein, and the animal's response was observed. The other group was challenged in the same way 21 days after the first injection, and the animal's response was observed. A positive reaction was defined as a reaction grade exceeding 2.
[0094] The scoring criteria for allergic reaction grades are shown in Table 1.
[0095] Table 1. Scoring criteria for allergic reaction grades
[0096]
[0097] The experimental results are shown in Table 2.
[0098] Table 2. Response scores for each group
[0099]
[0100] As shown in Table 2, at 14 and 21 days after the first injection, the allergic reaction scores and average scores of the cefminox sodium preparation group (Examples 1-5) and the saline group were both less than 2, while the allergic reaction scores and average scores of the ovalbumin group reached 4. This indicates that the cefminox sodium preparation (Examples 1-5) does not cause allergic reactions in mice and that the injection is safe.
[0101] Experiment Example 2
[0102] Test item: Cefminox sodium content stability test.
[0103] Experimental Methods: Using existing technology, a series of solutions were prepared, working curves were plotted, and regression equations were obtained. 1g of the formulations prepared in Examples 1-5 and Comparative Examples 1-12 were diluted with 1000mL of 0.9% sodium chloride injection, with water as a blank. The absorbance was measured at a wavelength of 272nm. The absorbance was substituted into the regression equation to calculate the cefminox sodium content at each time point, with the content at 0h as 100%. As the storage time increased, the relative content at other time points (after 2, 4, 6, 8, and 12 days) was calculated. It should be noted that the storage method was open exposure, with environmental conditions of 35℃±2℃, 65%±5%RH, and natural light irradiation.
[0104] Test results: such as Figures 1-3 As shown.
[0105] Results Analysis: In the preparation methods of Examples 1-5, the single variable was the amount of modified composite antioxidant used, which was 0.1g, 0.15g, 0.2g, 0.25g, and 0.3g, respectively. The results were obtained from... Figure 1 It can be seen that the cefminox sodium content changes of the formulations prepared in Examples 1-5 have a high degree of overlap with the growth of storage time, indicating that the amount of modified composite antioxidant is limited to 0.1-0.3 parts by weight, which will not significantly affect the stability of cefminox sodium content in the formulation. In addition, the cefminox sodium content in the formulation of Example 2 is slightly higher than that in the formulations of the other examples at each time point, indicating that Example 2 is the best example, and the weight ratio of each raw material component in Example 2 is the optimal ratio.
[0106] The only difference between Comparative Example 1 and Example 1 is the absence of sodium lactate Ringer's solution; the only difference between Comparative Example 2 and Example 1 is the absence of vitamin B12 injection; the only difference between Comparative Example 3 and Example 1 is the absence of both sodium lactate Ringer's solution and vitamin B12 injection; the only difference between Comparative Example 4 and Example 1 is the absence of the modified composite antioxidant; and the only difference between Comparative Example 5 and Example 1 is the absence of sodium lactate Ringer's solution, vitamin B12 injection, and the modified composite antioxidant. Results were obtained from... Figure 1 It can be seen that the presence of sodium lactate Ringer's solution, vitamin B12 injection, and modified compound antioxidants all contribute to improving the stability of cefminox sodium content in the formulation. The three work synergistically for better results; among the three, the modified compound antioxidants have the greatest effect.
[0107] The only difference between Comparative Example 4 and Example 1 is that the modified composite antioxidant was not used; the only difference between Comparative Example 6 and Example 1 is that the amount of modified composite antioxidant used is 0.05 g; the only difference between Comparative Example 7 and Example 1 is that the amount of modified composite antioxidant used is 0.35 g. Results are presented by... Figure 2It can be seen that the relative content change trend of cefminox in Comparative Example 6 is significantly lower than the overlapping trend range of Examples 1-5, indicating that the proportion of modified composite antioxidant is too low, resulting in a significant decrease in the stability of cefminox in the formulation. Similarly, the relative content change trend of cefminox in Comparative Example 7 is also significantly lower than the overlapping trend range of Examples 1-5, indicating that the proportion of modified composite antioxidant is too high, which not only fails to further improve the stability of cefminox but also causes a decrease in the stability of cefminox in the formulation. Of course, from... Figure 2 It can also be clearly seen that the overall trend of comparative examples 6 and 7 is higher than that of comparative example 4, indicating that as long as the modified composite antioxidant is present, it can play a role in improving the stability of cefminox sodium in the formulation.
[0108] The only difference between Comparative Example 8 and Example 1 is that the ultrasonic oscillations during the preparation of the modified composite antioxidant were replaced with mechanical stirring at 250 r / min; the only difference between Comparative Example 9 and Example 1 is that vitamin D was not used in the preparation of the modified composite antioxidant; the only difference between Comparative Example 10 and Example 1 is that vitamin C was not used in the preparation of the modified composite antioxidant; the only difference between Comparative Example 11 and Example 1 is that poloxamer was not used in the preparation of the modified composite antioxidant; the only difference between Comparative Example 12 and Example 1 is that poloxamer was replaced with phospholipids in the preparation of the modified composite antioxidant. Results were obtained from... Figure 3 It can be seen that during the preparation of modified composite antioxidants, changes in stirring conditions and the removal or replacement of any raw material will lead to a decrease in the performance of the prepared modified composite antioxidants in maintaining the stability of cefminox sodium in the formulation.
[0109] The above embodiments and comparative examples are retained because they have comparative and evidentiary value. In actual experiments, there are many similar comparisons, but they are not listed here to avoid repeating the evidentiary effect.
[0110] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.
[0111] Furthermore, various different embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention, they should also be regarded as the content disclosed by the present invention.
Claims
1. A cefminox sodium formulation for injection, characterized in that, By weight, it includes the following components: 1 part of cefminox sodium concentrate, 0.5 parts of sodium lactate Ringer's solution, 0.2 parts of vitamin B12 injection, 0.1-0.3 parts of modified compound antioxidant, and 3 parts of physiological saline. The preparation method of the modified composite antioxidant is as follows: S1. Add 1 part by weight of poloxamer to 20 parts by weight of distilled water and stir for 6-8 minutes to obtain a solution; S2. Pass 1 part by weight of natural vitamin C through a 100-mesh sieve and mix it into the solution obtained in S1. Then, sonicate for 10-15 minutes to obtain a vitamin C solution. S3. Mix 0.5 parts by weight of vitamin D into the vitamin C solution obtained in S2, and sonicate for 15-20 minutes to obtain the modified composite antioxidant.
2. The cefminox sodium formulation for injection according to claim 1, characterized in that, By weight, it comprises the following components: 1 part of premium cefminox sodium, 0.5 parts of sodium lactate Ringer's solution, 0.2 parts of vitamin B12 injection, 0.15 parts of modified compound antioxidant, and 3 parts of physiological saline.
3. The cefminox sodium preparation for injection according to claim 1 or 2, characterized in that, The preparation method of the cefminox sodium premium product is as follows: A1. Weigh 24g of crude cefminox sodium and put it into a beaker containing 250mL of deionized water. Stir for 20min at a speed of 300r / min to ensure complete dissolution and obtain a solution. A2. Weigh 0.24g of activated carbon and add it to the solution obtained in A1. Stir for 25 minutes, filter, and obtain the filtrate. A3. Transfer the filtrate into the crystallizer, turn on the stirrer, turn on the peristaltic pump, and pump 120 mL of ethanol into the crystallizer at a dropping rate of 6 mL / min. Turn off the peristaltic pump, weigh 2.4 g of seed crystals and add them to the crystallizer, continue stirring for 18 min at a stirring speed of 300 r / min, then stop stirring and grow the crystals for 85 min to obtain the crystal growth solution. A4. Turn on the peristaltic pump and pump 120 mL of ethanol into the crystal growth solution obtained in A3. Filter by suction, wash with acetone, collect the crystal product, and vacuum dry at 42°C for two hours to obtain the high-quality cefminox sodium.
4. The cefminox sodium formulation for injection according to claim 1, characterized in that, In S2, the frequency of ultrasonic oscillation is 80-100 kHz.
5. The cefminox sodium formulation for injection according to claim 4, characterized in that, In S3, the frequency of ultrasonic oscillation is 100-120 kHz.
6. The cefminox sodium formulation for injection according to claim 1, characterized in that, The saline solution is a 0.9% sodium chloride solution.
7. A method for preparing a cefminox sodium formulation for injection, characterized in that, The preparation of the cefminox sodium injection formulation as described in any one of claims 1-6 comprises the following steps: first, mixing sodium lactate Ringer's solution, vitamin B12 injection, modified composite antioxidant and physiological saline, and then adding cefminox sodium concentrate and mixing evenly to obtain the cefminox sodium injection formulation; in specific use, the cefminox sodium injection formulation is diluted with physiological saline.