Vitamin b6 injection and method for producing the same

Abstract

The application discloses a vitamin B6 injection, which comprises the following raw materials in weight: 100g / 1000ml of vitamin B6, 2-4g / 1000ml of an antioxidant, 3.5-5g / 1000ml of an anti-degradation agent, 1.1-1.5g / 1000ml of a stabilizer, and the rest is water for injection, wherein the stabilizer is a modified meglumine. The application aims at solving the technical problem of poor stability of the vitamin B6 injection.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and in particular relates to a vitamin B6 injection and its production method. Background Technology

[0002] Vitamin B6, also known as pyridoxine, exists in the body as a phosphate ester and 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, such as anemia, depression, and neuritis. Therefore, vitamin B6 supplementation is widely used in clinical treatment and nutritional health care.

[0003] Currently, in existing production processes, crude vitamin B6 is first obtained through a multi-step reaction. The finished product is then obtained through multiple recrystallizations in ethanol. This process involves many controllable factors and suffers from problems such as variations in purification conditions, low yield, and unstable product performance. Therefore, there is an urgent need to provide a vitamin B6 injection with good stability to meet people's demand for vitamin B6. Summary of the Invention

[0004] This invention provides a vitamin B6 injection and its production method, in order to solve the technical problem of poor stability of current vitamin B6.

[0005] In view of this, the present invention provides a vitamin B6 injection comprising the following raw materials by weight: 100g / 1000mL vitamin B6, 2-4g / 1000mL antioxidant, 3.5-5g / 1000mL anti-degradation agent, 1.1-1.5g / 1000mL stabilizer, with the remainder being water for injection, wherein the stabilizer is modified meglumine.

[0006] Optionally, the modified meglumine is prepared by the following method: acetic anhydride is placed in an ethanol solution and mixed evenly, meglumine is added, then a catalyst is added and mixed evenly, the mixture is heated, allowed to stand, reacted, distilled, concentrated, crystallized, filtered, and dried to obtain the modified meglumine.

[0007] Furthermore, the modified meglumine is prepared by the following method: acetic anhydride is placed in an ethanol solution and mixed evenly, meglumine is added, then a catalyst is added and mixed evenly, the temperature is heated to 30-50℃, allowed to stand, reacted for 3-5 hours, distilled, concentrated, crystallized, filtered, and dried to obtain the modified meglumine.

[0008] The amount of ethanol solution added per 1g of acetic anhydride is 25-35mL, the mass fraction of the ethanol solution is 70%, the weight ratio of meglumine to catalyst is 1:(0.01-0.03), and the catalyst is triethylamine.

[0009] Optionally, the weight ratio of acetic anhydride to meglumine is (0.6-1.5):1.

[0010] Optionally, the modified meglumine is further processed by the following method: the modified meglumine is placed in a methanol solution, mixed evenly, heated, activated carbon is added, reflux is carried out, filtered, the filtrate is collected, cooled, allowed to stand, crystallized, filtered, and dried to obtain the processed modified meglumine.

[0011] Furthermore, the modified meglumine is further processed by the following method: the modified meglumine is placed in a methanol solution, mixed evenly, heated to 50-70°C, activated carbon is added, refluxed for 1-2 hours, filtered, the filtrate is collected, cooled to 3-8°C, allowed to stand for 20-24 hours, crystallized, filtered, and dried to obtain the processed modified meglumine.

[0012] The amount of methanol solution added to each 1g of modified meglumine is 20-30mL, the mass fraction of the methanol solution is 80%, and the weight ratio of modified meglumine to activated carbon is 1:(0.004-0.008).

[0013] Optionally, the vitamin B6 is obtained by refining it through the following method: dissolving vitamin B6 in water, mixing evenly, adjusting the pH value, filtering through an ion exchange resin, collecting the filtrate, decolorizing, and crystallizing to obtain refined vitamin B6.

[0014] Furthermore, the vitamin B6 is obtained by the following method: dissolving vitamin B6 in water, mixing evenly, adjusting the pH value to 7-8 with sodium hydroxide solution, filtering through an ion exchange resin, collecting the filtrate, decolorizing, and crystallizing to obtain the refined vitamin B6.

[0015] The amount of water added to each 1g of vitamin B6 is 20-30mL, and the mass fraction of sodium hydroxide solution is 30%.

[0016] Optionally, the antioxidant is one or more of sodium bisulfite, sodium sulfite, and sodium metabisulfite.

[0017] Optionally, the anti-degradation agent is a mixture of ferulic acid and resveratrol.

[0018] Optionally, the weight ratio of ferulic acid to resveratrol is 1:1.

[0019] A method for producing a vitamin B6 injection includes the following steps:

[0020] S1: Add the stabilizer to the water for injection, mix well, adjust the pH value, heat the mixture, add the antioxidant and anti-degradation agent, mix well, and obtain the mixture.

[0021] S2: Add vitamin B6 to the mixture, mix well, adjust the pH value, and then filter, fill and sterilize to obtain vitamin B6 injection.

[0022] Furthermore, a method for producing a vitamin B6 injection includes the following steps:

[0023] S1: Add the stabilizer to water for injection, mix well, adjust the pH value to 6-7 with sodium hydroxide solution, heat to 40-50℃, add antioxidant and anti-degradation agent, mix well to obtain a mixture;

[0024] S2: Add vitamin B6 to the mixture, mix well, adjust the pH value to 2-3 with hydrochloric acid solution, and then filter, fill and sterilize to obtain vitamin B6 injection;

[0025] The sodium hydroxide solution has a mass fraction of 30%, and the hydrochloric acid solution has a mass fraction of 30%.

[0026] Optionally, in step S2, brown borosilicate ampoules are used for filling.

[0027] As can be seen from the above technical solutions, the embodiments of the present invention have the following advantages:

[0028] 1. This application uses modified meglumine as a stabilizer, and also combines it with antioxidants and anti-degradation agents to further improve the stability of vitamin B6 injection. In particular, the modified meglumine is prepared by modifying meglumine with acetic anhydride. The two react to introduce acetyl groups into the molecular structure of meglumine, which can better disperse it in vitamin B6 injection, enhance its interaction with vitamin B6, and thus better improve the antioxidant properties of vitamin B6, which helps to further improve the stability of vitamin B6 injection.

[0029] 2. This application also processes the modified meglumine by purifying it, which can further improve the purity of the modified meglumine, making it easier for it to exert its effects and further improve the stability of vitamin B6 injection.

[0030] 3. The vitamin B6 in this application is obtained through refining and purification, which can effectively remove impurities from vitamin B6, making it easier for vitamin B6 to exert its effects and improving the efficacy of vitamin B6 injections.

[0031] 4. This application uses ferulic acid and resveratrol together as anti-degradation agents. Ferulic acid contains double bonds and phenolic hydroxyl groups, which have a certain resistance to ultraviolet light and can protect vitamin B6 from photodegradation by scavenging free radicals and inhibiting oxidation reactions. Resveratrol has an antioxidant effect and can protect vitamin B6 from light damage. Through the combined action of ferulic acid and resveratrol, the resistance to photodegradation can be further improved, thereby improving the stability of vitamin B6. Detailed Implementation

[0032] To enable those skilled in the art to better understand the present invention, the technical solutions in the embodiments of the present invention are clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise specified, all raw materials, reagents, instruments, and equipment used in the present invention can be purchased on the market or prepared by existing methods.

[0033] Preparation Example

[0034] Preparation Example 1

[0035] A modified meglumine is prepared by the following method:

[0036] 1.2 kg of acetic anhydride was placed in a 70% ethanol solution and mixed thoroughly. Then, 2 kg of meglumine and 0.04 kg of triethylamine were added and mixed thoroughly. The mixture was heated to 40°C, allowed to stand, and reacted for 4 hours. The mixture was then distilled, concentrated, crystallized, filtered, and dried to obtain modified meglumine. The amount of ethanol solution added per 1 g of acetic anhydride was 30 mL.

[0037] Preparation Example 2

[0038] A modified meglumine differs from Preparation Example 1 in that the amount of acetic anhydride added is different; in Preparation Example 2, the amount of acetic anhydride added is 2.2 kg.

[0039] Preparation Example 3

[0040] A modified meglumine differs from Preparation Example 1 in that the amount of acetic anhydride added is different; in Preparation Example 3, the amount of acetic anhydride added is 3 kg.

[0041] Preparation Example 4

[0042] A modified meglumine differs from Preparation Example 1 in that the amount of acetic anhydride added is different; in Preparation Example 4, the amount of acetic anhydride added is 0.5 kg.

[0043] Preparation Example 5

[0044] A modified meglumine differs from Preparation Example 1 in that the amount of acetic anhydride added is different; in Preparation Example 5, the amount of acetic anhydride added is 5 kg.

[0045] Preparation Example 6

[0046] A type of vitamin B6 is obtained by refining it using the following method:

[0047] Vitamin B6 was dissolved in water and mixed evenly. The pH was adjusted to 7.5 with 30% sodium hydroxide. The mixture was then filtered through an ion exchange resin. The filtrate was collected, decolorized, and crystallized to obtain refined vitamin B6. The amount of water added to each 1g of vitamin B6 was 25mL.

[0048] Example

[0049] Example 1

[0050] A vitamin B6 injection, the proportions of its raw materials are shown in Table 1.

[0051] A method for producing a vitamin B6 injection includes the following steps;

[0052] S1: The stabilizer prepared in Preparation Example 1 is added to water for injection, mixed evenly, the pH value is adjusted to 6.5 with a 30% sodium hydroxide solution, the temperature is raised to 45°C, antioxidants and anti-degradation agents are added, and the mixture is mixed evenly to obtain a mixture.

[0053] S2: The vitamin B6 prepared in Preparation Example 6 was added to the mixture and mixed evenly. The pH value was adjusted to 2.5 with a 30% hydrochloric acid solution. After filtration, it was filled into brown borosilicate ampoules and sterilized to obtain vitamin B6 injection.

[0054] Examples 2-5

[0055] A vitamin B6 injection differs from Example 1 in that the raw material ratios of the injection are different, as shown in Table 1.

[0056] Table 1 Weight of each raw material

[0057]

[0058] Examples 6-9

[0059] A vitamin B6 injection differs from Example 5 in that the source of the stabilizer is different; the stabilizers in Examples 6-9 were prepared using Preparation Examples 2-5, respectively.

[0060] Example 10

[0061] A vitamin B6 injection differs from Example 6 in that the modified meglumine is further treated by the following method: the modified meglumine is placed in an 80% methanol solution, mixed evenly, heated to 60°C, activated carbon is added, refluxed for 1.5 hours, filtered, the filtrate is collected, cooled to 5°C, allowed to stand for 22 hours, crystallization occurs, filtered, and dried to obtain the treated modified meglumine; wherein, the amount of methanol solution added per 1g of modified meglumine is 25mL, and the weight ratio of modified meglumine to activated carbon is 1:0.006.

[0062] Comparative Example

[0063] Comparative Example 1

[0064] A vitamin B6 injection differs from Example 1 in that the stabilizer is replaced with meglumine in equal amounts.

[0065] Comparative Example 2

[0066] A vitamin B6 injection, which differs from Example 1 in that it does not contain a stabilizer.

[0067] Performance testing

[0068] The following performance tests were performed on the vitamin B6 injections in Examples 1-10 and Comparative Examples 1-2:

[0069] Stability test: Each injection was stored in one of the following environments for 10 days: high temperature 40℃, high temperature 60℃, and light irradiation of 5000lx±500lx. After 10 days, samples were taken to observe the properties, vitamin B6 content, single impurity content, and total impurity content of each injection. The test results are shown in Table 2.

[0070] Table 2 Detection Results

[0071]

[0072]

[0073]

[0074] As can be seen from Table 2, the vitamin B6 injection of this application, through the synergistic effect between the raw materials, exhibits superior stability under high temperature and strong light after being placed for 10 days under stability test conditions, based on its high vitamin B6 content and low single impurity content and total impurity content.

[0075] As can be seen from Examples 1-3, Example 2 showed better stability test results, indicating that the amount of stabilizer added in Example 2 was more appropriate. Too little stabilizer would not have a better effect, while too much stabilizer might disrupt the original balance and cause the stabilizer level to drop. Therefore, the stability of vitamin B6 injection can be better improved when the amount of stabilizer added is within a certain range.

[0076] As can be seen from Examples 4-5, the experimental results are not significantly different, indicating that variations in the amount of other raw materials besides the stabilizer within a certain range have little impact on the results of vitamin B6 injection.

[0077] As can be seen from Examples 5-9, Example 6 showed better results in the stabilizer test, indicating that the stabilizer prepared in Preparation Example 2 was more suitable. That is, the amount of acetic anhydride and meglumine added in Preparation Example 2 was more appropriate. If the amount of acetic anhydride added was too small, the modification effect on meglumine would be poor, and it would not play a better stabilizing role for vitamin B6. If the amount of acetic anhydride added was too large, it might damage the structure of meglumine, affect the reactivity, and ultimately lead to a decrease in stability. Therefore, only when the amount of acetic anhydride and meglumine added is within a certain range can the stability of vitamin B6 injection be improved more effectively.

[0078] Combining Examples 6 and 10, it can be seen that Example 10 showed better results in the stabilizer test, indicating that the modified meglumine is more suitable after processing. Further purification removes impurities, making it easier to exert its effects and further improving the stability of vitamin B6 injection.

[0079] The above-described embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A vitamin B6 injection, characterized in that: The raw materials include the following components by weight: Vitamin B6 100g / 1000mL, antioxidant 2-4g / 1000mL, anti-degradation agent 3.5-5g / 1000mL, stabilizer 1.1-1.5g / 1000mL, and the remainder is water for injection, wherein the stabilizer is modified meglumine.

2. The vitamin B6 injection according to claim 1, characterized in that: The modified meglumine is prepared by the following method: acetic anhydride is placed in an ethanol solution and mixed evenly, meglumine is added, then a catalyst is added and mixed evenly, the mixture is heated, allowed to stand, reacted, distilled, concentrated, crystallized, filtered, and dried to obtain the modified meglumine.

3. The vitamin B6 injection according to claim 1, characterized in that: The weight ratio of acetic anhydride to meglumine is (0.6-1.5):

1.

4. The vitamin B6 injection according to claim 2, characterized in that: The modified meglumine is further processed by the following method: the modified meglumine is placed in a methanol solution, mixed evenly, heated, activated carbon is added, reflux is carried out, filtered, the filtrate is collected, cooled, allowed to stand, crystallized, filtered, and dried to obtain the processed modified meglumine.

5. The vitamin B6 injection according to claim 1, characterized in that: The vitamin B6 is obtained by refining it as follows: dissolving vitamin B6 in water, mixing it evenly, adjusting the pH value, filtering it through an ion exchange resin, collecting the filtrate, decolorizing it, and crystallizing it to obtain the refined vitamin B6.

6. The vitamin B6 injection according to claim 1, characterized in that: The antioxidant is one or more of sodium bisulfite, sodium sulfite, and sodium metabisulfite.

7. The vitamin B6 injection according to claim 1, characterized in that: The anti-degradation agent is a mixture of ferulic acid and resveratrol.

8. The vitamin B6 injection according to claim 7, characterized in that, The weight ratio of ferulic acid to resveratrol is 1:

1.

9. A method for producing a vitamin B6 injection as described in claims 1-8, characterized in that: Includes the following steps: S1: Add the stabilizer to the water for injection, mix well, adjust the pH value, heat the mixture, add the antioxidant and anti-degradation agent, mix well, and obtain the mixture. S2: Add vitamin B6 to the mixture, mix well, adjust the pH value, and then filter, fill and sterilize to obtain vitamin B6 injection.

10. The method for producing vitamin B6 injection according to claim 9, characterized in that: In step S2, brown borosilicate ampoules are used for filling.

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