Vitamin B6 injection and preparation method thereof

Abstract

The invention discloses a vitamin B6 injection and a preparation method thereof, and relates to the field of medical technology. Each mL of the injection contains the following raw materials and auxiliary materials: vitamin B6, arginine, meglumine, and glutathione; the preparation method comprises the following steps: S1, weighing the prescribed amount of vitamin B6, arginine and glutathione, adding them to water for injection, stirring and dissolving, and obtaining a primary mixed solution; S2, adding a sodium hydroxide solution with a mass fraction of 10% to the primary mixed solution, and adjusting the pH value to 2.5; S3, adding the prescribed amount of meglumine to the solution obtained in step S2, stirring and dissolving, filtering after standing, and obtaining a secondary mixed solution; S4, making the secondary mixed solution volume with water for injection, filling, sealing and terminal sterilization according to specifications, and obtaining a vitamin B6 injection. The vitamin B6 injection prepared by the invention has good clarity, is non-irritating, has high stability, is not easy to oxidize, has a small increase in related substances, has no problem of drug solution adhesion, is easy to operate, and has low production cost.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a vitamin B6 injection and a preparation method thereof. Background Art

[0002] Vitamin B6 (VB6) was discovered in the 1930s. It is a water-soluble vitamin belonging to the B group. It is easily destroyed by light or alkali and is not resistant to high temperatures. VB6 is a general term for a class of easily convertible 2-methyl-3-hydroxypyridine compounds, including six different forms: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP). VB6 is a micronutrient necessary for maintaining healthy growth and normal physiological functions of animals, but higher animals such as humans cannot synthesize VB6 by themselves and must obtain it from the diet. The main food sources are meat, fish and poultry.

[0003] Fresenius Kabi, an American company, first developed and marketed vitamin B6 products in 1972 (hereinafter referred to as the original research enterprise). The original research enterprise's prescription contains raw material vitamin B6, antibacterial agent chlorobutanol, pH adjuster sodium hydroxide, and solvent water for injection. Since vitamin B6 injection is sensitive to high temperature, the original research product uses a sterilization filtration process for it, and the antibacterial agent chlorobutanol is added to the prescription. However, chlorobutanol is slightly toxic and long-term use will cause harm to the human body.

[0004] Existing vitamin B6 injection can be summarized into three categories: one is the same as the original research product, in order to control the lower impurity level of the product, a sterile filtration process with lower safety assurance is selected, and in order to improve the antibacterial performance, the antibacterial agent trichlorobutanol, which is harmful to the human body, must be added. The second is a vitamin B6 injection filled in a plastic ampoule and a preparation method thereof as disclosed in CN111544377A, which improves the stability of vitamin B6 by the combined use of calcium sodium edetate and sodium dihydrogen phosphate, and the packaging adopts a plastic ampoule bottle to achieve the purpose of reducing the amount of insoluble particles. The product has a complex prescription and does not solve the problem that vitamin B6 is easily decomposed by light. The use of a light-transmitting plastic ampoule bottle requires more attention to light-proof storage, which undoubtedly increases the safety risks and inconveniences in the production and storage process. The third is a vitamin B6 injection and a preparation method thereof as disclosed in CN117598985A, which requires nitrogen filling and filling to control the residual oxygen content. The product is complicated to operate, which is not conducive to large-scale production, and will cause certain difficulties in the quality control of the final product. At the same time, the existing vitamin B6 injection is prone to foaming during the filling process. When filled in an ampoule, the liquid medicine will adhere to the bottle mouth, and the liquid medicine will be carbonized during the ampoule sealing process, making the product unqualified with visible foreign matter, reducing the product yield, and also increasing the unknown safety of the patient's medication. Therefore, a simpler and safer preparation method of vitamin B6 injection is urgently needed. Summary of the invention

[0005] In view of the above-mentioned defects of the prior art, the present invention proposes a method for preparing vitamin B6 injection to solve the problems raised by the above-mentioned background technology.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] A vitamin B6 injection, each mL of which contains the following raw materials and auxiliary materials: 90-120 mg of vitamin B6, 12-20 mg of arginine, 1-6 mg of meglumine, and 0.1-0.5 mg of glutathione.

[0008] Preferably, a vitamin B6 injection contains the following raw materials and auxiliary materials per mL of injection: 100 mg vitamin B6, 15 mg arginine, 5 mg meglumine, and 0.3 mg glutathione.

[0009] Preferably, a method for preparing vitamin B6 injection comprises the following steps:

[0010] S1. Weigh the prescribed amount of vitamin B6, arginine and glutathione, add them to water for injection, stir and dissolve to obtain a primary mixed solution;

[0011] S2, adding 8-15% by mass of sodium hydroxide solution to the primary mixed solution obtained in step S1, and adjusting the pH value to 2.0-3.0;

[0012] S3, adding a prescribed amount of meglumine to the solution obtained in step S2, stirring to dissolve, letting stand for 10 to 20 minutes, and then filtering with a 0.22 μm polyethersulfone filter membrane to obtain a secondary mixed solution;

[0013] S4. Make up the volume of the secondary mixed solution with water for injection to a filling volume of 1.05 ml / vial, fill it into 2 ml brown medium borosilicate glass ampoule, seal it with a sealing machine and perform terminal sterilization to obtain vitamin B6 injection.

[0014] Preferably, the materials used for stirring in steps S1 and S3 are glass containers and glass stirring paddles.

[0015] Preferably, the mass fraction of the sodium hydroxide solution in step S2 is 10%.

[0016] Preferably, in step S2, the pH value is adjusted to 2.5.

[0017] Preferably, the filling container material of the vitamin B6 injection in step S4 is a brown borosilicate glass ampoule.

[0018] Preferably, the terminal sterilization process parameters of step S4 are a sterilization temperature of 121° C. and a sterilization time of 12 to 15 minutes.

[0019] Preferably, the storage conditions of the vitamin B6 injection in step S4 are a temperature of 40-50° C. and a light-proof environment.

[0020] Preferably, the prepared vitamin B6 injection is used for subcutaneous injection.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] The technical scheme of the present invention is different from the prior art. No antioxidant disodium edetate and antibacterial agent chlorobutanol are added, and no nitrogen protection is performed during the preparation process. The present invention utilizes arginine, meglumine, glutathione and vitamin B6 to react with each other. The prepared vitamin B6 injection has good clarity, no irritation, high stability, is not easy to oxidize, has a small amount of impurities in the sterilization process, has no liquid adhesion problem, is easy to operate, and has low production cost. In addition, the pH value is controlled within a specific range during the preparation process, the content of related substances is controlled, and a specific sterilization process is combined, so that the prepared vitamin B6 injection has good stability. DETAILED DESCRIPTION

[0023] The technical solution of the present invention is further described in detail below in conjunction with specific implementation methods.

[0024] 1. The active ingredient in the prescription is vitamin B6, and the inactive ingredients (excipients) are: water for injection (solvent) and sodium hydroxide (pH adjuster).

[0025] Reference preparation information

[0026]

[0027] Example 1

[0028] A vitamin B6 injection, each mL of injection contains the following raw materials and excipients: 90 mg of vitamin B6, 12 mg of arginine, 1 mg of meglumine, and 0.1 mg of glutathione.

[0029] A method for preparing vitamin B6 injection comprises the following steps:

[0030] S1. Weigh the prescribed amount of vitamin B6, arginine and glutathione, add them to water for injection, and stir and dissolve them in a glass container and a glass stirring paddle to obtain a primary mixed solution;

[0031] S2, adding 8% by mass sodium hydroxide solution to the primary mixed solution obtained in step S1, and adjusting the pH value to 2.0;

[0032] S3, adding a prescribed amount of meglumine to the solution obtained in step S2, stirring and dissolving with a glass container and a glass stirring paddle, and filtering with a 0.22 μm polyethersulfone filter membrane after standing for 10 minutes to obtain a secondary mixed solution;

[0033] S4. Make up the volume of the secondary mixed solution with water for injection to a filling volume of 1.05 ml / vial, and fill it into 2 ml brown medium borosilicate glass ampoule. Use a sealing machine to seal the ampoule and sterilize it at 121°C for 12 min to obtain vitamin B6 injection.

[0034] Example 2

[0035] A vitamin B6 injection, each mL of injection contains the following raw materials and excipients: 120 mg of vitamin B6, 20 mg of arginine, 6 mg of meglumine, and 0.5 mg of glutathione.

[0036] A method for preparing vitamin B6 injection comprises the following steps:

[0037] S1. Weigh the prescribed amount of vitamin B6, arginine and glutathione, add them to water for injection, and stir and dissolve them in a glass container and a glass stirring paddle to obtain a primary mixed solution;

[0038] S2, adding a 15% by mass sodium hydroxide solution to the primary mixed solution obtained in step S1, and adjusting the pH value to 3.0;

[0039] S3, adding a prescribed amount of meglumine to the solution obtained in step S2, stirring and dissolving in a glass container with a glass stirring paddle, and filtering with a 0.22 μm polyethersulfone filter membrane after standing for 20 minutes to obtain a secondary mixed solution;

[0040] S4. Make up the volume of the secondary mixed solution with water for injection to a filling volume of 1.05 ml / vial, and fill it into 2 ml brown medium borosilicate glass ampoules. Use a sealing machine to seal the ampoule and sterilize it at 121°C for 15 min to obtain vitamin B6 injection.

[0041] Example 3

[0042] A vitamin B6 injection, each mL of injection contains the following raw materials and excipients: 100 mg of vitamin B6, 15 mg of arginine, 5 mg of meglumine, and 0.3 mg of glutathione.

[0043] A method for preparing vitamin B6 injection comprises the following steps:

[0044] S1. Weigh the prescribed amount of vitamin B6, arginine and glutathione, add them to water for injection, and stir and dissolve them in a glass container and a glass stirring paddle to obtain a primary mixed solution;

[0045] S2, adding a 10% sodium hydroxide solution to the initial mixed solution obtained in step S1, and adjusting the pH value to 2.5;

[0046] S3, adding a prescribed amount of meglumine to the solution obtained in step S2, stirring and dissolving in a glass container with a glass stirring paddle, and filtering with a 0.22 μm polyethersulfone filter membrane after standing for 15 minutes to obtain a secondary mixed solution;

[0047] S4. Make up the volume of the secondary mixed solution with water for injection to a filling volume of 1.05 ml / vial, and fill it into 2 ml brown medium borosilicate glass ampoule. Use a sealing machine to seal the ampoule and sterilize it at 121°C for 12 min to obtain vitamin B6 injection.

[0048] Comparative Example 1

[0049] The difference from Example 3 is that arginine is replaced by lysine, and the other components and steps remain unchanged.

[0050] A vitamin B6 injection, each mL of injection contains the following raw materials and auxiliary materials: 100 mg of vitamin B6, 15 mg of lysine, 5 mg of meglumine, and 0.3 mg of glutathione.

[0051] A method for preparing vitamin B6 injection comprises the following steps:

[0052] S1. Weigh the prescribed amount of vitamin B6, lysine and glutathione, add them to water for injection, and stir and dissolve them in a glass container and a glass stirring paddle to obtain a primary mixed solution;

[0053] S2, adding a 10% sodium hydroxide solution to the initial mixed solution obtained in step S1, and adjusting the pH value to 2.5;

[0054] S3, adding a prescribed amount of meglumine to the solution obtained in step S2, stirring and dissolving in a glass container with a glass stirring paddle, and filtering with a 0.22 μm polyethersulfone filter membrane after standing for 15 minutes to obtain a secondary mixed solution;

[0055] S4. Make up the volume of the secondary mixed solution with water for injection to a filling volume of 1.05 ml / vial, and fill it into 2 ml brown medium borosilicate glass ampoule. Use a sealing machine to seal the ampoule and sterilize it at 121°C for 12 min to obtain vitamin B6 injection.

[0056] Comparative Example 2

[0057] The difference from Example 3 is that there is no meglumine in the raw and auxiliary materials, and the other ingredients and steps remain unchanged.

[0058] A vitamin B6 injection, each mL of injection contains the following raw materials and auxiliary materials: 100 mg of vitamin B6, 15 mg of arginine, and 0.3 mg of glutathione.

[0059] A method for preparing vitamin B6 injection comprises the following steps:

[0060] S1. Weigh the prescribed amount of vitamin B6, arginine and glutathione, add them to water for injection, and stir and dissolve them in a glass container and a glass stirring paddle to obtain a primary mixed solution;

[0061] S2, adding a 10% sodium hydroxide solution to the primary mixed solution obtained in step S1, adjusting the pH value to 2.5, letting it stand for 15 minutes, and filtering it with a 0.22 μm polyethersulfone filter membrane to obtain a secondary mixed solution;

[0062] S4. Make up the volume of the secondary mixed solution with water for injection to a filling volume of 1.05 ml / vial, and fill it into 2 ml brown medium borosilicate glass ampoule. Use a sealing machine to seal the ampoule and sterilize it at 121°C for 12 min to obtain vitamin B6 injection.

[0063] Comparative Example 3

[0064] The difference from Example 3 is that there is no glutathione in the raw materials and the other ingredients and steps remain unchanged.

[0065] A vitamin B6 injection, each mL of injection contains the following raw materials and excipients: 100 mg of vitamin B6, 15 mg of arginine, and 5 mg of meglumine.

[0066] A method for preparing vitamin B6 injection comprises the following steps:

[0067] S1. Weigh the prescribed amount of vitamin B6 and arginine and add them to water for injection. Stir and dissolve them in a glass container and a glass stirring paddle to obtain a primary mixed solution.

[0068] S2, adding a 10% sodium hydroxide solution to the initial mixed solution obtained in step S1, and adjusting the pH value to 2.5;

[0069] S3, adding a prescribed amount of meglumine to the solution obtained in step S2, stirring and dissolving in a glass container with a glass stirring paddle, and filtering with a 0.22 μm polyethersulfone filter membrane after standing for 15 minutes to obtain a secondary mixed solution;

[0070] S4. Make up the volume of the secondary mixed solution with water for injection to a filling volume of 1.05 ml / vial, and fill it into 2 ml brown medium borosilicate glass ampoule. Use a sealing machine to seal the ampoule and sterilize it at 121°C for 12 min to obtain vitamin B6 injection.

[0071] Comparative Example 4

[0072] The difference from Example 3 is that the preparation method is one-time mixing, and the other ingredients and steps remain unchanged.

[0073] A vitamin B6 injection, each mL of injection contains the following raw materials and excipients: 100 mg of vitamin B6, 15 mg of arginine, 5 mg of meglumine, and 0.3 mg of glutathione.

[0074] A method for preparing vitamin B6 injection comprises the following steps:

[0075] S1. Weigh the prescribed amount of vitamin B6, arginine, glutathione and meglumine, add them to water for injection, stir and dissolve them in a glass container and a glass stirring paddle to obtain a primary mixed solution;

[0076] S2, adding a 10% sodium hydroxide solution to the initial mixed solution obtained in step S1, and adjusting the pH value to 2.5;

[0077] S3, the solution obtained in step S2 was allowed to stand for 15 minutes and then filtered through a 0.22 μm polyethersulfone filter membrane to obtain a secondary mixed solution;

[0078] S4. Make up the volume of the secondary mixed solution with water for injection to a filling volume of 1.05 ml / vial, and fill it into 2 ml brown medium borosilicate glass ampoule. Use a sealing machine to seal the ampoule and sterilize it at 121°C for 12 min to obtain vitamin B6 injection.

[0079] Comparative Example 5

[0080] According to patent application number 202311367390.1, the patent name is a vitamin B6 injection and a vitamin B6 injection prepared by the preparation method described in Example 1 in the preparation method thereof.

[0081] Comparative Example 6

[0082] Vitamin B6 injection prepared by the preparation method described in Example 1 of patent application number 202311595505.2, patent name is a method for preparing a highly stable vitamin B6 injection.

[0083] Comparative Example 7

[0084] According to patent application number 202010330436.2, the patent name is "Vitamin B6 injection filled in a plastic ampoule and its preparation method," which is a vitamin B6 injection prepared by the preparation method described in Example 1.

[0085] Test Example 1

[0086] 1.1 Take the vitamin B6 injection prepared in Examples 1 to 3 and the reference preparation as the control group to test the basic properties, content of related substances and stability of the vitamin B6 injection.

[0087] 1.2 Test results

[0088] The results are shown in Table 1 and Table 2:

[0089] Table 1 Sample testing

[0090]

[0091]

[0092] Table 2 10-day results of influencing factors

[0093]

[0094] Conclusion: From Table 1 and Table 2, it can be seen that the properties, color, pH value, related substances, content, visible foreign matter, insoluble particles, etc. of the samples are in compliance with the regulations. The results of the influencing factors for 10 days show that this product is unstable under high temperature conditions, but the vitamin B6 prepared by the present invention is more stable than the reference preparation.

[0095] Test Example 2 Investigation of Chlorobutanol and pH Range

[0096] 2.1 The Technical Guidance for the Development of Injectable Drugs (Draft for Comments) points out that the use of antibacterial agents in injections should be strictly controlled, and in principle, it is not recommended to use antibacterial agents. The chlorobutanol in the reference preparation of this product is an antibacterial agent. This product uses a terminal sterilization process, which can effectively reduce the risk of contamination. Therefore, after removing the chlorobutanol in the prescription composition, the samples were prepared using the sterilization filtration process and the terminal sterilization process, and the results of the related substances, pH value, etc. of this product were compared.

[0097] 2.2 Test method: In addition to different pH parameters, 7 batches of samples with different pH values ​​(sample 1, sample 2, sample 3, sample 4, sample 5, sample 6 and sample 7) were prepared according to the method of Example 3, and the pH optimum values ​​were investigated. The batch size was 100 ml per batch, and the samples were placed under the influencing factors (high temperature 40°C, high temperature 60°C, light 5000lx) for 10 days to investigate the changes in solution stability under different pH conditions. At the same time, after selecting the optimum pH value, chlorobutanol was added to the sample to prepare a sample (sample 8) to investigate the changes in the content of related substances.

[0098] 2.3 The test results are shown in Table 3:

[0099] Table 3 Tests in different pH ranges and investigation of chlorobutanol

[0100]

[0101]

[0102] Conclusion: Comparing samples with different pH values, when the pH value of the solution is between 2.0 and 3.0, under the conditions of 0-day and 10-day influencing factors, the properties, color, content (0 day) and related substances all meet the quality requirements. When the pH value is higher than 3.0 or lower than 2.0, the properties turn yellow on 0 day, the related substances exceed the limit, and the related substances increase significantly under the conditions of 10-day influencing factors. Therefore, the pH control process of the pH solution of this product is tentatively set to be 2.0-3.0, and the preferred pH is 2.5.

[0103] As can be seen from Table 3, excluding chlorobutanol from the formulation has no effect on the key quality attributes of the product within a certain pH range. At the same time, by comparing the samples with chlorobutanol added, i.e., sample 3 and sample 8, it can be seen that the addition of chlorobutanol will increase the content of related substances, while the arginine, meglumine and glutathione contained in sample 3 will not increase the content of related substances. Therefore, chlorobutanol can be omitted from the formulation.

[0104] Test Example 3: Investigation of the dosage of added edetate disodium

[0105] 3.1 During the investigation of the material of the liquid preparation container, it was found that the color of the liquid turned yellow under high temperature conditions when a stainless steel container was used for liquid preparation, indicating that metal ions had a certain influence on the stability of vitamin B6 injection. Disodium edetate, as a metal ion complexing agent commonly used in the preparation process of vitamin B6 injection, can complex the metal ions generated in the liquid preparation container and stainless steel pipeline during the production process to protect the liquid from being affected. It was designed to use a stainless steel beaker and a stirring paddle for preparation. Example 3 was used as the test group (a 306 stainless steel beaker + a stainless steel paddle was used as the stirring container). On the basis of the raw and auxiliary materials of Example 3, disodium edetate (0%, 0.3%, 0.5%, and 0.8%) of different masses of raw and auxiliary materials were added as samples 9, 10, 11, and 12, respectively, to investigate the changes in elemental impurities, color, related substances, and pH of the liquid before and after the addition.

[0106] 3.3 The test results are shown in Table 4:

[0107] Table 4 Edetate disodium dosage investigation

[0108]

[0109]

[0110] Conclusion: From Table 4, it can be seen that the samples with different dosages of edetate disodium added to the prescription will increase the related substances of the samples after testing, and exceed the limit, especially the single impurity exceeds the limit; the related substances increase significantly after 10 days of exposure to influencing factors under different conditions. Edetate disodium will have an impact on this product, while the samples without edetate disodium added are all within the limit range. Combined with the results of the preparation temperature and preparation material investigation, it is tentatively decided that edetate disodium will not be added to the prescription composition of this product.

[0111] Test Example 4 Investigation of Solution Stability under Different Storage Environments

[0112] 4.1 Detection method: The concentration of this product is 100 mg / ml, and the amount of raw materials used is large. The storage temperature may affect the quality of the liquid medicine, which needs to be investigated. The study was carried out according to 200 ml per batch. The vitamin B6 injection prepared in Example 3 was taken separately, and three groups (sample 13, sample 14 and sample 15) of samples were set up at room temperature (25-30°C), 40-50°C and 60-80°C in a light-proof environment for 8 hours. The pH value, content, and changes in related substances.

[0113] 4.2 The test results are shown in Table 5:

[0114] Table 5 Solution stability

[0115]

[0116] Conclusion: From Table 5, it can be seen that the content of the drug solution did not change significantly after being placed at room temperature, 40-50℃, and 60-80℃ for 0, 4, and 8 hours. The total impurities increased at room temperature, but the increase was small. The longer the storage time at 60-80℃, the faster the related substances increased. Therefore, subsequent investigations should minimize storage under high temperature conditions to avoid the growth of related substances.

[0117] Test Example 5 Investigation of the material of the liquid mixing container

[0118] 5.1 During the production process, the liquid will directly contact materials such as stainless steel during the preparation, filtration, and filling processes, which may introduce metal ions and affect the quality of the liquid. Therefore, the impact of the use of stainless steel materials in the preparation process on this product is investigated.

[0119] 5.2 Samples 16 and 17 were prepared using the raw material and auxiliary material ratios of Example 3, wherein Sample 16 used a glass beaker + glass stirring paddle, and Sample 17 used 306 material + stainless steel paddle (the paddle was worn), and the test was carried out at 40-50°C.

[0120] 5.3 The test results are shown in Table 6:

[0121] Table 6 Test of different liquid preparation container materials

[0122]

[0123] Conclusion: From Table 6, we can see that different liquid preparation materials have no effect on the related substances of the liquid, but have an effect on the color of the liquid. The liquid preparation using a container made of 306 stainless steel and a damaged stirring paddle will change color. Therefore, in the production process, a glass container beaker + glass stirring paddle must be used for the liquid preparation container.

[0124] Test Example 6: Nitrogen Protection Investigation

[0125] 6.1 This experiment mainly examines the effect of nitrogen filling on the preparation during the filling process, and places the samples under influencing factors (high temperature 40℃, high temperature 60℃, light 5000lux) for 10 days and 30 days to examine the changes in solution stability.

[0126] 6.2 Example 3 was used as the test group. Based on the process of Example 3, nitrogen was filled for 5 seconds as sample 18 and the reference preparation was used as the control group.

[0127] 6.3 The test results are shown in Table 7:

[0128] Table 7 Nitrogen protection investigation

[0129]

[0130]

[0131] Conclusion: It can be seen from Table 7 that the properties, color, pH value, related substances and content of nitrogen-filled and non-nitrogen-filled samples on day 0 and influencing factors on day 10 all meet the requirements. Therefore, the non-nitrogen-filled process is selected for the preparation of this product.

[0132] Test Example 7 Animal Irritation Test

[0133] 7.1 Test materials

[0134] The vitamin B6 injection prepared in Example 3 and Comparative Examples 1 to 7 was subjected to an irritation test with reference to the technical guidelines for the study of drug irritation, allergy and hemolysis in China. The experimental animals were rabbits, and a test group (represented by the injection of Example 3), a control group (Comparative Examples 1 to 7) and a blank group (normal saline) were set. The test group, the control group and the blank group of this test were all administered subcutaneously at a dosing volume of 1.2 mg / kg on the back (rabbit hair removed), with a dose of 1.2 mg / kg, and 3 rabbits in each group.

[0135] 7.2 Observation of subcutaneous irritation symptoms

[0136] Observe the injection site with the naked eye before administration and 24h and 48h after administration, score the reaction of the subcutaneous injection site according to the skin irritation reaction evaluation standard, and evaluate the irritation intensity of subcutaneous injection according to the skin irritation intensity grading standard. The skin irritation reaction scoring standard is shown in Table 8, and the subcutaneous injection irritation intensity grading standard is shown in Table 9;

[0137] Table 8 Skin irritation reaction scoring standard

[0138]

[0139] Table 9 Classification standard of irritation intensity of subcutaneous injection

[0140] Integral mean Strength score 0～0.49 Non-irritating 0.5～1.99 Mild irritant 2.0～5.99 Moderate irritation 6.0～8.0 Strong irritation

[0141] 7.3 Irritation test results

[0142] As shown in Table 10:

[0143] Table 10 Irritation test

[0144]

[0145] As shown in Table 10, the vitamin B6 injection of the present invention is non-irritating when used for subcutaneous injection and is safe to use. Comparison between Example 3 and Comparative Examples 1 to 4 shows that the selection of raw materials and the preparation method are very important for the technical solution. Even if arginine is replaced with lysine, the same technical effect cannot be achieved. Vitamin B6 can interact with arginine, meglumine and glutathione to avoid irritation caused by injection of vitamin B6 injection. Comparison between Example 3 and Comparative Examples 5 to 7 shows that the vitamin B6 injection prepared by the prior art has a certain irritation to the injection site.

[0146] Test Example 8 Active ingredient content

[0147] 8.1 Test materials

[0148] The vitamin B6 injection prepared in Example 3 and Comparative Examples 1 to 7 was tested for the content of active ingredients according to the relevant content of the determination of vitamin B6 content in the 2005 edition of the Chinese Pharmacopoeia, that is, the determination was carried out according to the high performance liquid chromatography method (Appendix ⅤD). Chromatographic conditions and system suitability test, using octadecyl oxane bonded silica gel as filler; 0.04% sodium pentane sulfonate solution (adjusting the pH value to 3.0 with glacial acetic acid)-methanol (85:15) as mobile phase, and the detection wavelength was 291nm. The number of theoretical plates calculated based on the vitamin B6 peak is not less than 4000. Determination method Take an appropriate amount of this product, accurately weigh it, add the mobile phase to dissolve it and quantitatively dilute it to make a solution containing about 0.1mg per 1ml. Accurately measure 10μl. Inject it into the liquid chromatograph and record the chromatogram; take an appropriate amount of vitamin B6 reference substance, accurately weigh it, and determine it in the same way. Calculate it by peak area according to the external standard method to obtain.

[0149] 8.2 Test Results

[0150] The active ingredient content is shown in Table 11:

[0151] Table 11 Vitamin B6 content

[0152]

[0153] As can be seen from Table 11, the vitamin B6 content in Example 3 is the highest, indicating that the drug takes effect quickly after being injected into the body.

[0154] Test Example 9 Yield Calculation

[0155] The product yields of the vitamin B6 injections prepared in Example 3 and Comparative Examples 1 to 7 were calculated. The results are shown in Table 12:

[0156] Table 12 Product yield

[0157]

[0158] It can be seen from the results in Table 12 that the vitamin B6 injection prepared in Comparative Examples 5 to 6 is prone to have the drug solution adhered to the ampoule mouth during the filling process, resulting in the carbonization of the drug solution adhered to the bottle mouth when the ampoule bottle is sealed at high temperature, making the injection solution unqualified due to visible foreign matter, thereby reducing the product yield; while in Example 3, since the drug solution does not bubble and there is no adhesion to the ampoule mouth, its yield is greatly improved. Comparative Examples 1 to 4 lack arginine, meglumine, glutathione and the preparation method is changed, resulting in an unsatisfactory drug solution state, with a small amount of adhesion at the bottle mouth, indicating that the addition of complete raw and auxiliary materials and different preparation methods have an impact on the product yield.

[0159] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A vitamin B6 injection, characterized in that: Each mL of injection solution is composed of the following raw materials and excipients: 90-120 mg of vitamin B6, 12-20 mg of arginine, 1-6 mg of meglumine, 0.1-0.5 mg of glutathione, an appropriate amount of 8-15% sodium hydroxide solution, and the balance is water for injection. The preparation method of the vitamin B6 injection comprises the following steps: S1. Weigh the prescribed amount of vitamin B6, arginine and glutathione, add them to water for injection, stir and dissolve to obtain a primary mixed solution; S2, adding sodium hydroxide solution to the initial mixed solution obtained in step S1 to adjust the pH value to 2.0-3.0; S3, adding a prescribed amount of meglumine to the solution obtained in step S2, stirring to dissolve, letting stand for 10 to 20 minutes and then filtering to obtain a secondary mixed solution; S4. The secondary mixed solution is made up to volume with water for injection, and the solution is filled, sealed and terminally sterilized according to the specifications to obtain the vitamin B6 injection solution; The materials used for stirring in steps S1 and S3 are glass containers and glass stirring paddles.

2. A vitamin B6 injection according to claim 1, characterized in that: Each mL of injection solution is composed of the following raw materials and auxiliary materials: 100 mg of vitamin B6, 15 mg of arginine, 5 mg of meglumine, 0.3 mg of glutathione, an appropriate amount of 10% sodium hydroxide solution by mass, and the balance is water for injection.

3. The method for preparing a vitamin B6 injection according to claim 1, characterized in that: In step S2, the pH value is adjusted to 2.

5.

4. The method for preparing a vitamin B6 injection according to claim 1, characterized in that: The filling container material of the vitamin B6 injection in step S4 is a brown borosilicate glass ampoule.

5. The method for preparing a vitamin B6 injection according to claim 1, characterized in that: The terminal sterilization process parameters of step S4 are sterilization temperature 121° C. and sterilization time 12 to 15 minutes.

6. The method for preparing a vitamin B6 injection according to claim 1, characterized in that: The storage conditions of the vitamin B6 injection in step S4 are a temperature of 40 to 50° C. and a light-proof environment.

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