A high-stability vitamin B6 injection and preparation method thereof

Abstract

The present invention relates to the field of medical technology, and in particular to a highly stable vitamin B6 injection and a preparation method thereof. In the present invention, each 1000ml of the highly stable vitamin B6 injection contains, in addition to 100g of vitamin B6, 2.5-3.5g of an antioxidant, 3.6-4.5g of an antidegradant and 1.2-1.5g of a stabilizer. The antioxidant is one or more of sodium bisulfite, sodium pyrosulfite and sodium thiosulfate, the antidegradant is N-acetylcysteine, and the stabilizer is taurine and meglumine. The highly stable vitamin B6 injection provided by the present invention has high stability, and after undergoing 6 months of accelerated stability testing, the content of related substances is less than 0.05%, which is far below the pharmacopoeia standard.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a highly stable vitamin B6 injection and its preparation method. Background Art

[0002] Vitamin B6, also known as pyridoxine, is a water-soluble vitamin belonging to the vitamin B complex. It plays a crucial role in various physiological processes in the human body, including amino acid metabolism, nerve conduction, and immune function. Vitamin B6 not only participates in catalyzing and regulating the activity of many enzymes but also plays an important role in fetal development and erythrocyte production. Modern medical research has found that vitamin B6 deficiency may lead to a range of health problems, including anemia, depression, and neuritis. Therefore, vitamin B6 supplementation is widely used in clinical treatment and nutritional health care.

[0003] However, the properties of vitamin B6 present many challenges during storage and use. First, its water solubility results in varying stability under different temperature conditions. At high temperatures or in alkaline environments, vitamin B6 rapidly degrades, forming inactive metabolites. Furthermore, prolonged storage or exposure to strong light can easily lead to oxidation, further reducing its biological activity. Summary of the Invention

[0004] In view of this, the purpose of this invention is to provide a highly stable vitamin B6 injection solution and its preparation method, so as to solve the problems of short storage time and poor stability of vitamin B6 injection solution.

[0005] To achieve the above objectives, the present invention provides a highly stable vitamin B6 injection solution, wherein each 1000ml of injection solution contains 100g of vitamin B6, as well as 2.5-3.5g of antioxidant, 3.6-4.5g of anti-degradation agent and 1.2-1.5g of stabilizer.

[0006] Preferably, the antioxidant is one or more of sodium bisulfite, sodium metabisulfite, and sodium thiosulfate.

[0007] Preferably, the anti-degradation agent is N-acetylcysteine.

[0008] Preferably, the stabilizer is taurine and meglumine.

[0009] Preferably, the content of meglumine in the stabilizer is 20wt%-30wt%.

[0010] Preferably, the content of related substances in the highly stable vitamin B6 injection solution is less than 0.05% after 6 months at 40°C and 75% relative humidity.

[0011] Furthermore, the present invention also provides a method for preparing a highly stable vitamin B6 injection solution, the specific preparation steps of which are as follows:

[0012] (1) Dissolve taurine and meglumine in 200 ml of water for injection at 25-30℃, and adjust the pH with sodium hydroxide.

[0013] (2) Heat to 40-45℃, add antioxidants and anti-degradation agents, stir to dissolve, and add water for injection to 400ml;

[0014] (3) Keep the temperature at 40-45℃, add vitamin B6, stir to dissolve, then add water for injection to 1000ml and adjust the pH with sodium hydroxide;

[0015] (4) After filtration through a 0.22μm filter, the solution is filled according to specifications and then sterilized at 121℃ for 15-20 minutes to obtain a highly stable vitamin B6 injection.

[0016] Preferably, in step (1), the pH is adjusted to 6-7.

[0017] Preferably, in step (3), the pH is adjusted to 2.5-3.

[0018] Preferably, the filter membrane material in step (4) is one of polypropylene or polyethersulfone.

[0019] Preferably, brown borosilicate glass ampoules are used for filling in step (4).

[0020] The beneficial effects of this invention are:

[0021] The high-stability vitamin B6 injection provided by this invention has a high vitamin B6 content and extremely low related substance content, which meets the pharmacopoeia standard. After being placed at 65°C and under strong light (6000 lx) for 20 days, it still has a high vitamin B6 content and extremely low related substance content. At the same time, after undergoing a 6-month accelerated stability test, it still has a low related substance content.

[0022] The highly stable vitamin B6 injection provided by this invention uses taurine and meglumine as stabilizers, combined with antioxidants and anti-degradation agents, to further improve the stability of vitamin B6 injection. In particular, even trace amounts of meglumine can greatly improve the stability of vitamin B6 injection, resulting in unexpected and significant effects.

[0023] Sodium bisulfite and N-acetylcysteine ​​in this invention can act as sacrificial reducing agents to prevent vitamin B6 from being destroyed during high-temperature sterilization, which is a significant improvement over vitamin B6 injection prepared by traditional formulas. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments.

[0025] Example 1:

[0026] (1) Dissolve 0.96g taurine and 0.24g meglumine in 200ml of water for injection at 25℃, and adjust the pH to 6.2 with sodium hydroxide.

[0027] (2) Heat to 40℃, add 2.5g sodium bisulfite and 3.6g N-acetylcysteine, stir to dissolve, and add water for injection to 400ml;

[0028] (3) Keep the temperature at 40℃, add 100g of vitamin B6, stir to dissolve, then add water for injection to 1000ml and adjust the pH with sodium hydroxide to 2.6;

[0029] (4) After filtration through a 0.22μm polypropylene filter, the solution is filled into brown borosilicate glass ampoules according to specifications and then sterilized at 121℃ for 15 minutes to obtain a highly stable vitamin B6 injection solution.

[0030] Example 2:

[0031] (1) Dissolve 1g of taurine and 0.35g of meglumine in 200ml of water for injection at 25℃, and adjust the pH to 6.4 with sodium hydroxide.

[0032] (2) Heat to 40℃, add 3g sodium bisulfite and 4g N-acetylcysteine, stir to dissolve, and add water for injection to 400ml;

[0033] (3) Keep the temperature at 40℃, add 100g of vitamin B6, stir to dissolve, then add water for injection to 1000ml and adjust the pH with sodium hydroxide to 2.8;

[0034] (4) After filtration through a 0.22μm polypropylene filter, the solution is filled into brown borosilicate glass ampoules according to specifications and then sterilized at 121℃ for 18 minutes to obtain a highly stable vitamin B6 injection solution.

[0035] Example 3:

[0036] (1) Dissolve 1.05g taurine and 0.45g meglumine in 200ml of water for injection at 30℃, and adjust the pH to 6.8 with sodium hydroxide.

[0037] (2) Heat to 45℃, add 3.5g sodium bisulfite and 4.5g N-acetylcysteine, stir to dissolve, and add water for injection to 400ml;

[0038] (3) Keep the temperature at 45℃, add 100g of vitamin B6, stir to dissolve, then add water for injection to 1000ml and adjust the pH with sodium hydroxide to 2.9;

[0039] (4) After filtering through a 0.22μm polyethersulfone filter, the solution is filled into brown borosilicate glass ampoules according to specifications and then sterilized at 121℃ for 20 minutes to obtain a highly stable vitamin B6 injection solution.

[0040] Comparative Example 1:

[0041] (1) Dissolve 3g sodium bisulfite and 4g N-acetylcysteine ​​in 400ml of water for injection at 40℃;

[0042] (2) Keep the temperature at 40℃, add 100g of vitamin B6, stir to dissolve, then add water for injection to 1000ml and adjust the pH with sodium hydroxide to 2.7;

[0043] (3) After filtering through a 0.22μm polypropylene filter, the solution is filled into brown borosilicate glass ampoules according to specifications and then sterilized at 121℃ for 18 minutes to obtain vitamin B6 injection solution.

[0044] The difference between Comparative Example 1 and Example 2 is that no stabilizer was added.

[0045] Comparative Example 2:

[0046] (1) Dissolve 1g of taurine in 200ml of water for injection at 25℃, and adjust the pH to 6.4 with sodium hydroxide;

[0047] (2) Heat to 40℃, add 3g sodium bisulfite and 4g N-acetylcysteine, stir to dissolve, and add water for injection to 400ml;

[0048] (3) Keep the temperature at 40℃, add 100g of vitamin B6, stir to dissolve, then add water for injection to 1000ml and adjust the pH with sodium hydroxide to 2.8;

[0049] (4) After filtering through a 0.22μm polypropylene filter, the solution is filled into brown borosilicate glass ampoules according to specifications and then sterilized at 121℃ for 18 minutes to obtain vitamin B6 injection solution.

[0050] The difference between Comparative Example 2 and Example 2 is that no meglumine was added.

[0051] Comparative Example 3:

[0052] (1) Dissolve 1g of taurine and 0.35g of meglumine in 200ml of water for injection at 25℃, and adjust the pH to 6.4 with sodium hydroxide.

[0053] (2) Heat to 40℃, add 100g of vitamin B6, stir to dissolve, then add water for injection to 1000ml and adjust the pH to 2.8 with sodium hydroxide;

[0054] (3) After filtering through a 0.22μm polypropylene filter, the solution is filled into brown borosilicate glass ampoules according to specifications and then sterilized at 121℃ for 18 minutes to obtain vitamin B6 injection solution.

[0055] The difference between Comparative Example 3 and Example 2 is that sodium bisulfite and N-acetylcysteine ​​were not added.

[0056] Comparative Example 4:

[0057] (1) Dissolve 1g of taurine and 0.35g of meglumine in 200ml of water for injection at 25℃, and adjust the pH to 6.4 with sodium hydroxide.

[0058] (2) Heat to 40℃, add 3g sodium bisulfite, stir to dissolve, and add water for injection to 400ml;

[0059] (3) Keep the temperature at 40℃, add 100g of vitamin B6, stir to dissolve, then add water for injection to 1000ml and adjust the pH with sodium hydroxide to 2.8;

[0060] (4) After filtering through a 0.22μm polypropylene filter, the solution is filled into brown borosilicate glass ampoules according to specifications and then sterilized at 121℃ for 18 minutes to obtain vitamin B6 injection solution.

[0061] The difference between Comparative Example 4 and Example 2 is that N-acetylcysteine ​​was not added.

[0062] Comparative Example 5:

[0063] (1) Dissolve 1g of taurine and 0.35g of meglumine in 200ml of water for injection at 25℃, and adjust the pH to 6.4 with sodium hydroxide.

[0064] (2) Heat to 40℃, add 4g N-acetylcysteine, stir to dissolve, and add water for injection to 400ml;

[0065] (3) Keep the temperature at 40℃, add 100g of vitamin B6, stir to dissolve, then add water for injection to 1000ml and adjust the pH with sodium hydroxide to 2.8;

[0066] (4) After filtering through a 0.22μm polypropylene filter, the solution is filled into brown borosilicate glass ampoules according to specifications and then sterilized at 121℃ for 18 minutes to obtain vitamin B6 injection solution.

[0067] The difference between Comparative Example 5 and Example 2 is that sodium bisulfite was not added.

[0068] For ease of understanding, the experimental data of the examples and comparative examples are presented in Table 1, as shown below.

[0069] Table 1 Experimental Data

[0070]

[0071]

[0072] As can be seen from Examples 1-3 in Table 1, the vitamin B6 injection obtained by using the prescription provided by the present invention has a high content and extremely low content of related substances, which meets the pharmacopoeia standards.

[0073] As can be seen from Comparative Examples 1-5 in Table 1, sodium bisulfite and N-acetylcysteine ​​help reduce the content of related substances in vitamin B6 injection. This is mainly because sodium bisulfite and N-acetylcysteine ​​can act as sacrificial reducing agents to prevent vitamin B6 from being destroyed during high-temperature sterilization. Furthermore, the combination of taurine and meglumine also helps to further reduce the content of related substances in vitamin B6 injection.

[0074] The samples prepared in the examples and comparative examples were subjected to influencing factor tests. They were placed at 65°C and under strong light (6000 lx) for 20 days to examine the stability of the samples. The results are shown in Table 2.

[0075] Table 2 Results of High Temperature and Strong Light Test

[0076]

[0077] As can be seen from the data of Examples 1-3 in Table 2, the highly stable vitamin B6 injection provided by the present invention still has a high vitamin B6 content and extremely low content of related substances after being placed at 65°C and under strong light (6000 lx) for 20 days, indicating that it has excellent stability under high temperature and strong light.

[0078] As can be seen from the data in Table 2 of Example 2 and Comparative Examples 1-5, sodium bisulfite and N-acetylcysteine ​​are crucial for maintaining the stability of vitamin B6 injection under high temperature and strong light. Furthermore, taurine and meglumine can further improve the stability. In particular, even trace amounts of meglumine can greatly improve the stability of vitamin B6 injection, showing unexpected and significant effects.

[0079] The samples prepared in the examples and comparative examples were subjected to accelerated stability tests. They were placed at 40°C and 75% relative humidity for 6 months to examine their stability. The results are shown in Table 3.

[0080] Table 3 Results of accelerated stability test

[0081]

[0082] As can be seen from the data of Examples 1-3 in Table 3, after 6 months of accelerated testing, the vitamin B6 injection provided by the present invention still has a low content of related substances and excellent stability. As can be seen from the data of Comparative Examples 1-5, they all show different degrees of degradation, and the content of related substances far exceeds the pharmacopoeia standard, indicating that the vitamin B6 injection prepared by the formula provided by the present invention has significant progress compared with the vitamin B6 injection prepared by the traditional formula.

[0083] Those skilled in the art should understand that the discussion of any of the above embodiments is merely illustrative and is not intended to imply that the scope of the present invention is limited to these examples. Within the scope of the present invention, the technical features in the above embodiments or different embodiments may be combined, the steps may be implemented in any order, and there are many other variations of the different aspects of the present invention as described above, which are not provided in detail for the sake of simplicity.

Claims

1. A highly stable vitamin B6 injection, characterized in that: Each 1000ml injection contains, in addition to 100g of vitamin B6, 2.5-3.5g of antioxidant, 3.6-4.5g of antidegradant and 1.2-1.5g of stabilizer; The antioxidant is one or more of sodium bisulfite, sodium pyrosulfite and sodium thiosulfate; The antidegradant is N-acetylcysteine; The stabilizer is taurine and meglumine; the content of meglumine in the stabilizer is 20wt%-30wt%.

2. The highly stable vitamin B6 injection according to claim 1, characterized in that: The high-stability vitamin B6 injection has a content of related substances less than 0.05% after 6 months at 40° C. and 75% relative humidity.

3. A method for preparing a highly stable vitamin B6 injection according to any one of claims 1 to 2, characterized in that: The specific preparation steps are as follows: (1) Dissolve taurine and meglumine in 200 ml of water for injection at 25-30°C, and adjust the pH with sodium hydroxide. (2) Raise the temperature to 40-45°C, add antioxidant and antidegradant, stir to dissolve, and add water for injection to 400 ml; (3) Maintaining the temperature at 40-45°C, add vitamin B6, stir to dissolve, then add water for injection to 1000 ml and adjust the pH with sodium hydroxide; (4) Filter through a 0.22µm filter, fill according to specifications, and then sterilize at 121℃ for 15-20min to obtain a highly stable vitamin B6 injection.

4. The method for preparing the highly stable vitamin B6 injection according to claim 3, characterized in that: In the step (1), the pH is adjusted to 6-7.

5. The method for preparing the highly stable vitamin B6 injection according to claim 3, characterized in that: In step (3), the pH is adjusted to 2.5-3.

6. The method for preparing the highly stable vitamin B6 injection according to claim 3, characterized in that: The filter membrane material in the filter in step (4) is one of polypropylene and polyethersulfone.

7. The method for preparing the highly stable vitamin B6 injection according to claim 3, characterized in that: In step (4), brown medium borosilicate glass ampoules are used for filling.

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