A water-soluble vitamin preparation for injection and its preparation method

Abstract

This invention relates to a water-soluble vitamin preparation for injection and its preparation method, belonging to the field of pharmaceutical preparations. The preparation method of the water-soluble vitamin preparation for injection includes weighing raw materials, dissolving, sterile filtration, filling, freeze-drying, stoppering, and capping. In existing formulation systems for water-soluble vitamin preparations for injection, this invention mainly achieves room temperature operation throughout the dissolving process by constructing a graded feeding system based on the relative differences in vitamin water solubility and utilizing the synergistic effect of a pulsed magnetic field-ultrasound composite field at an appropriate frequency. This eliminates the need for additional solubilizers and heating operations, resulting in minimal temperature fluctuations during the dissolving process. This improves the stability of the obtained vitamin preparation and the efficiency of the preparation process, providing a new technical means for the preparation of water-soluble vitamin preparations for injection.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparations, and more particularly to a water-soluble vitamin preparation for injection and its preparation method. Background Technology

[0002] In the field of pharmaceutical preparations, injectable water-soluble vitamin preparations are a crucial class of drugs, playing a key role in meeting the body's urgent need for various water-soluble vitamins. Water-soluble vitamins, as trace organic substances essential for maintaining normal physiological functions, play an indispensable role in numerous physiological processes such as metabolism, growth and development, and immune regulation. However, the human body often cannot synthesize sufficient amounts of water-soluble vitamins, or the need for them increases significantly under certain special physiological and disease conditions. In such cases, rapid and accurate supplementation of water-soluble vitamins via injection becomes particularly necessary.

[0003] Currently, various methods for preparing water-soluble vitamin preparations for injection have been reported in existing technical literature, such as the technical solutions disclosed in patent documents CN103110656A, CN101904862A, and CN1824309A. However, these existing methods generally require heating during the dissolution of vitamins in water for injection, resulting in significant temperature fluctuations throughout the solution preparation process, which affects the stability of the resulting water-soluble vitamin preparation for injection. Summary of the Invention

[0004] To address the above problems, this invention provides a water-soluble vitamin preparation for injection and its preparation method.

[0005] In a first aspect, the present invention provides a method for preparing a water-soluble vitamin preparation for injection, the method comprising weighing raw materials, preparing solution, sterilizing filtration, filling, freeze drying, stoppering and capping.

[0006] The solution preparation includes the following process:

[0007] Folic acid, biotin, thiamine nitrate and vitamin B12 are mixed to obtain the first vitamin mixture;

[0008] Vitamin B6, nicotinamide, sodium vitamin C, sodium riboflavin phosphate, and sodium pantothenate are mixed to obtain a second vitamin mixture;

[0009] Under a pulsed magnetic field-ultrasound combined field and an inert gas atmosphere, freeze-drying protectant, antioxidant, metal ion chelating agent, first vitamin mixture and second vitamin mixture were added to water for injection in batches and stirred at room temperature. Then, the pH of the system was adjusted to 5.3~5.8 with a pH adjuster and water for injection was added to the total volume to obtain the drug solution.

[0010] The ratio Y of the ultrasonic frequency F2 and the pulse magnetic field frequency F1 ranges from 2 × 10⁻⁶. 3 -6×10 3 .

[0011] Furthermore, the operating conditions parameters of the pulsed magnetic field-ultrasound composite field include: the pulsed magnetic field frequency is 10Hz~20Hz, the pulsed magnetic field voltage is 70V~100V, the ultrasonic frequency is 40kHz~60kHz, and the ultrasonic power is 100W~200W.

[0012] Furthermore, Y is 4×10 3 .

[0013] Furthermore, the operating parameters of the pulsed magnetic field-ultrasound composite field include: the pulsed magnetic field frequency is 15Hz, the pulsed magnetic field voltage is 80V, the ultrasonic frequency is 60kHz, and the ultrasonic power is 165W.

[0014] Further, under a pulsed magnetic field-ultrasound combined field and an inert gas atmosphere, a freeze-drying protectant, an antioxidant, a metal ion chelating agent, the first vitamin mixture, and the second vitamin mixture are added to water for injection in batches and stirred at room temperature. The pH of the system is then adjusted to 5.3-5.8 with a pH adjuster, and water for injection is added to the total volume to obtain the drug solution. The steps include the following:

[0015] In an inert gas atmosphere, 75-85 vol% of the total volume of water for injection is added to a container and an ultrasonic vibrating rod is inserted at the center of the container. Then, a pulsed magnetic field is applied to the outside of the container.

[0016] Simultaneously turn on the ultrasonic generator and the pulsed magnetic field generator, then add the freeze-drying protectant, antioxidant and metal ion chelating agent in batches, and stir at room temperature for 2-5 minutes for the first time, stir at room temperature for 2-5 minutes for the first vitamin mixture, and stir at room temperature for 2-5 minutes for the second vitamin mixture. Finally, adjust the pH of the system to 5.3-5.8 with a pH adjuster, add water for injection to the full volume, and stir at room temperature for 2-5 minutes to obtain the drug solution.

[0017] Furthermore, based on 3 ml of water for injection, the dosage of folic acid added is 0.38 mg to 0.42 mg;

[0018] Based on 3 ml of water for injection, the dosage of vitamin B6 added is 4.8 mg to 5.0 mg;

[0019] Based on 3 ml of water for injection, the dosage of biotin added is 58 μg to 62 μg;

[0020] Based on 3 ml of water for injection, the dosage of the added riboflavin sodium phosphate is 4.8 mg to 5.0 mg.

[0021] Based on 3 ml of water for injection, the dosage of vitamin B12 added is 4.8 μg to 5.2 μg;

[0022] Based on 3 ml of water for injection, the dosage of thiamine nitrate added is 2.8 mg to 3.2 mg;

[0023] Based on 3 ml of water for injection, the dosage of sodium pantothenate added is 16.0 mg to 17.0 mg;

[0024] Based on 3 ml of water for injection, the dosage of nicotinamide added is 39.0 mg to 41.0 mg;

[0025] Based on 3 ml of water for injection, the dosage of added sodium vitamin C is 111 mg to 115 mg;

[0026] Based on 3 ml of water for injection, the dosage of the freeze-drying protectant added is 295 mg to 305 mg;

[0027] Based on 3 ml of water for injection, the dosage of the metal ion chelating agent added is 490 μg to 505 μg;

[0028] The dosage of the antioxidant added is 3.5 mg to 4.0 mg, based on 3 ml of water for injection.

[0029] Furthermore, based on 3 ml of water for injection, the dosage of folic acid added is 0.4 mg;

[0030] Based on 3 ml of water for injection, the added dose of vitamin B6 is 4.9 mg;

[0031] Based on 3 ml of water for injection, the added dose of biotin is 60 μg;

[0032] Based on 3 ml of water for injection, the dosage of the added riboflavin sodium phosphate is 4.9 mg;

[0033] Based on 3 ml of water for injection, the added dose of vitamin B12 is 5.0 μg;

[0034] Based on 3 ml of water for injection, the dosage of thiamine nitrate added is 3.1 mg;

[0035] Based on 3 ml of water for injection, the added dose of sodium pantothenate is 16.5 mg;

[0036] The dosage of nicotinamide added is 40.0 mg, calculated based on 3 ml of water for injection.

[0037] Based on 3 ml of water for injection, the added dose of sodium vitamin C is 113.0 mg;

[0038] The dosage of the freeze-drying protectant added is 300.0 mg, calculated based on 3 ml of water for injection.

[0039] The dosage of the metal ion chelating agent added is 500.0 μg, based on 3 ml of water for injection.

[0040] Based on 3 ml of water for injection, the dosage of the antioxidant added is 3.8 mg.

[0041] Furthermore, the freeze-drying protectant includes glycine, the metal ion chelating agent includes disodium edetate, the antioxidant includes sodium bisulfite, and the pH adjuster includes a sodium hydroxide solution with a mass fraction of 0.5-0.8%.

[0042] Furthermore, the freeze-drying step includes the following processes:

[0043] When the temperature of the freeze-drying apparatus drops to -8℃ to -5℃, place the liquid medicine to be dried into the apparatus and maintain it for 30 min to 60 min. Then, cool the apparatus at a rate of 20℃ / min to 25℃ / min to -20℃ to -10℃ and maintain it for 1.5 h to 2.5 h. Next, cool the apparatus at a rate of 10℃ / min to 15℃ / min to -45℃ to -40℃ and maintain it for 2.5 h to 3.5 h. Finally, evacuate the apparatus to a vacuum degree of <0.1 Mbar and raise the temperature at a rate of 1 to 5℃ / min to 20℃ to 22℃ and maintain it for 4 h to 5 h.

[0044] Secondly, based on the same inventive concept, the present invention provides a water-soluble vitamin preparation for injection, wherein the water-soluble vitamin preparation for injection is prepared by the method for preparing water-soluble vitamin preparations for injection described in the first aspect.

[0045] The technical solutions provided in the embodiments of the present invention have at least the following advantages compared with the prior art:

[0046] This invention provides a water-soluble vitamin preparation for injection and its preparation method. In the existing formulation system of water-soluble vitamin preparations for injection, this invention mainly achieves room temperature operation throughout the entire solution preparation process by constructing a graded feeding system based on the relative differences in vitamin water solubility and utilizing the synergistic effect of a pulsed magnetic field-ultrasound composite field at an appropriate frequency. This eliminates the need for additional solubilizers and heating operations, resulting in no significant temperature fluctuations during the solution preparation process. This improves the stability of the obtained vitamin preparation and the efficiency of the preparation process, providing a new technical means for the preparation of water-soluble vitamin preparations for injection. Detailed Implementation

[0047] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. 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.

[0048] Unless otherwise specified, all raw materials, reagents, instruments, and equipment used in this invention can be purchased commercially or prepared using existing methods. Furthermore, unless otherwise specified or detailed, the steps and parameters involved in this invention, such as sterile filtration (e.g., using a 0.22μm filter membrane), filling, stoppering, and capping, can be performed according to the preparation processes of water-soluble vitamin preparations for injection disclosed in prior art patent documents CN103110656A, CN101904862A, and CN1824309A, or directly using existing equipment. These will not be elaborated upon further in this invention document.

[0049] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed according to national standards. If no corresponding national standard exists, then generally accepted international standards, conventional conditions, or conditions recommended by the manufacturer are followed. Example 1

[0050] This example provides a water-soluble vitamin preparation for injection. Based on 3 ml of water for injection, the formulation system of the water-soluble vitamin preparation for injection is as follows:

[0051] The dosage of folic acid added is 0.4 mg;

[0052] The dosage of added vitamin B6 is 4.9 mg;

[0053] The dosage of biotin added was 60 μg;

[0054] The dosage of riboflavin sodium added was 4.9 mg;

[0055] The dosage of vitamin B12 added was 5.0 μg;

[0056] The dosage of thiamine nitrate added was 3.1 mg;

[0057] The dosage of sodium pantothenate added was 16.5 mg;

[0058] The dosage of nicotinamide added was 40.0 mg;

[0059] The dosage of added sodium vitamin C is 113.0 mg;

[0060] The dosage of the freeze-drying protectant (specifically glycine) added is 300.0 mg;

[0061] The dosage of the metal ion chelating agent (specifically disodium edetate) added was 500.0 μg;

[0062] The dosage of the antioxidant (specifically sodium bisulfite) added was 3.8 mg.

[0063] The preparation method of the above-mentioned water-soluble vitamin preparation for injection includes weighing raw materials, preparing solutions, sterilizing filtration, filling, freeze drying, stoppering, and capping.

[0064] The solution preparation includes the following steps: mixing folic acid, biotin, thiamine nitrate, and vitamin B12 to obtain a first vitamin mixture; mixing vitamin B6, nicotinamide, sodium vitamin C, sodium riboflavin phosphate, and sodium pantothenate to obtain a second vitamin mixture; adding 80 vol% of the total volume of water for injection into a container under a nitrogen atmosphere and inserting an ultrasonic vibrator at the center of the container, then applying a pulsed magnetic field to the outside of the container; simultaneously turning on the ultrasonic generator and the pulsed magnetic field generator, and then sequentially adding a freeze-drying protectant, an antioxidant, and a metal... The ion chelating agent was stirred at 150 rpm for 3 minutes at room temperature. The first vitamin mixture was stirred at 150 rpm for 3 minutes at room temperature. The second vitamin mixture was stirred at 150 rpm for 3 minutes at room temperature. Finally, the pH of the system was adjusted to 5.5 with a pH adjuster (specifically, a 0.6% sodium hydroxide solution). After adding water for injection to the full volume, the mixture was stirred at 150 rpm for 3 minutes at room temperature to obtain the drug solution. The ratio Y of the ultrasonic frequency F2 to the pulse magnetic field frequency F1 was 4 × 10⁻⁶. 3Specifically: the pulse magnetic field frequency is 15Hz, the pulse magnetic field voltage is 80V, the ultrasonic frequency is 60kHz, and the ultrasonic power is 165W.

[0065] The freeze-drying process includes the following steps: when the temperature of the freeze-drying apparatus drops to -6°C, the liquid medicine to be dried is placed in and kept for 45 min; the temperature is lowered to -15°C at a rate of 22°C / min and kept for 2.0 h; then the temperature is lowered to -43°C at a rate of 12°C / min and kept for 3.0 h; then a vacuum is drawn to a vacuum degree of <0.1 Mbar and the temperature is raised to 21°C at a rate of 3.5°C / min and kept for 4.5 h. Example 2

[0066] This example provides a water-soluble vitamin preparation for injection. Based on 3 ml of water for injection, the formulation system of the water-soluble vitamin preparation for injection is as follows:

[0067] The dosage of folic acid added is 0.38 mg;

[0068] The dosage of added vitamin B6 is 4.8 mg;

[0069] The dosage of biotin added was 58 μg;

[0070] The dosage of riboflavin sodium phosphate added was 4.8 mg;

[0071] The dosage of vitamin B12 added was 4.8 μg;

[0072] The dosage of thiamine nitrate added was 2.8 mg;

[0073] The dosage of sodium pantothenate added was 16.0 mg;

[0074] The dosage of nicotinamide added was 39.0 mg;

[0075] The dosage of added sodium vitamin C is 111 mg;

[0076] The dosage of the freeze-drying protectant (specifically glycine) added was 295 mg;

[0077] The dosage of the metal ion chelating agent (specifically disodium edetate) added was 490 μg;

[0078] The dosage of the antioxidant (specifically sodium bisulfite) added is 3.5 mg.

[0079] The preparation method of the above-mentioned water-soluble vitamin preparation for injection includes weighing raw materials, preparing solutions, sterilizing filtration, filling, freeze drying, stoppering, and capping.

[0080] The solution preparation includes the following steps: mixing folic acid, biotin, thiamine nitrate, and vitamin B12 to obtain a first vitamin mixture; mixing vitamin B6, nicotinamide, sodium vitamin C, sodium riboflavin phosphate, and sodium pantothenate to obtain a second vitamin mixture; adding 75 vol% of the total volume of water for injection into a container under a nitrogen atmosphere and inserting an ultrasonic vibrator at the center of the container, then applying a pulsed magnetic field to the outside of the container; simultaneously turning on the ultrasonic generator and the pulsed magnetic field generator, and then sequentially adding a freeze-drying protectant, an antioxidant, and a metal... The ion chelating agent was stirred at 150 rpm for 5 minutes at room temperature. The first vitamin mixture was stirred at 150 rpm for 5 minutes at room temperature, and the second vitamin mixture was stirred at 150 rpm for 5 minutes at room temperature. Finally, the pH of the system was adjusted to 5.3 with a pH adjuster (specifically, a 0.5% sodium hydroxide solution). After adding water for injection to the full volume, the mixture was stirred at 150 rpm for 5 minutes at room temperature to obtain the drug solution. The ratio Y of the ultrasonic frequency F2 to the pulse magnetic field frequency F1 was 2 × 10⁻⁶. 3 Specifically: the pulse magnetic field frequency is 20Hz, the pulse magnetic field voltage is 100V, the ultrasonic frequency is 40kHz, and the ultrasonic power is 200W;

[0081] The freeze-drying process includes the following steps: when the temperature of the freeze-drying apparatus drops to -8°C, the liquid medicine to be dried is placed in and kept for 30 minutes; the temperature is lowered to -10°C at a rate of 20°C / min and kept for 2.5 hours; then the temperature is lowered to -40°C at a rate of 10°C / min and kept for 3.5 hours; then a vacuum is drawn to a vacuum degree of <0.1 Mbar and the temperature is increased to 20°C at a rate of 1°C / min and kept for 4 hours. Example 3

[0082] This example provides a water-soluble vitamin preparation for injection. Based on 3 ml of water for injection, the formulation system of the water-soluble vitamin preparation for injection is as follows:

[0083] The dosage of folic acid added is 0.42 mg;

[0084] The dosage of added vitamin B6 is 5.0 mg;

[0085] The dosage of biotin added was 62 μg;

[0086] The dosage of riboflavin sodium phosphate added is 5.0 mg;

[0087] The dosage of vitamin B12 added was 5.2 μg;

[0088] The dosage of thiamine nitrate added was 3.2 mg;

[0089] The dosage of sodium pantothenate added was 17.0 mg;

[0090] The dosage of nicotinamide added was 41.0 mg;

[0091] The dosage of added sodium vitamin C is 115 mg;

[0092] The dosage of the freeze-drying protectant (specifically glycine) added was 305 mg;

[0093] The dosage of the metal ion chelating agent (specifically disodium edetate) added was 505 μg;

[0094] The dosage of the antioxidant (specifically sodium bisulfite) added was 4.0 mg.

[0095] The preparation method of the above-mentioned water-soluble vitamin preparation for injection includes weighing raw materials, preparing solutions, sterilizing filtration, filling, freeze drying, stoppering, and capping.

[0096] The solution preparation includes the following steps: mixing folic acid, biotin, thiamine nitrate, and vitamin B12 to obtain a first vitamin mixture; mixing vitamin B6, nicotinamide, sodium vitamin C, sodium riboflavin phosphate, and sodium pantothenate to obtain a second vitamin mixture; adding 85 vol% of the total volume of water for injection into a container under a nitrogen atmosphere and inserting an ultrasonic vibrator at the center of the container, then applying a pulsed magnetic field to the outside of the container; simultaneously turning on the ultrasonic generator and the pulsed magnetic field generator, and then sequentially adding a freeze-drying protectant, an antioxidant, and a metal... The ion chelating agent was stirred at 150 rpm for 2 minutes at room temperature. The first vitamin mixture was stirred at 150 rpm for 2 minutes at room temperature. The second vitamin mixture was stirred at 150 rpm for 2 minutes at room temperature. Finally, the pH of the system was adjusted to 5.8 with a pH adjuster (specifically, a 0.8% sodium hydroxide solution). After adding water for injection to the full volume, the mixture was stirred at 150 rpm for 2 minutes at room temperature to obtain the drug solution. The ratio Y of the ultrasonic frequency F2 to the pulse magnetic field frequency F1 was 6 × 10⁻⁶. 3 Specifically: the pulse magnetic field frequency is 10Hz, the pulse magnetic field voltage is 70V, the ultrasonic frequency is 60kHz, and the ultrasonic power is 100W;

[0097] The freeze-drying process includes the following steps: when the temperature of the freeze-drying apparatus drops to -5°C, the liquid medicine to be dried is placed in and kept for 60 min; the temperature is lowered to -20°C at a rate of 25°C / min and kept for 1.5 h; then the temperature is lowered to -45°C at a rate of 15°C / min and kept for 2.5 h; then a vacuum is drawn to a vacuum degree of <0.1 Mbar and the temperature is raised to 22°C at a rate of 5°C / min and kept for 5 h.

[0098] Comparative Example 1

[0099] This example provides a water-soluble vitamin preparation for injection and its preparation method, which differs from Example 1 only in that:

[0100] (1) During the preparation of the solution, all vitamin raw materials are added to the water for injection. The specific process is as follows: Under a nitrogen atmosphere, 80 vol% of the total volume of water for injection is added to the container and an ultrasonic vibrator is inserted at the center of the container. Then, a pulsed magnetic field is applied to the outside of the container. At the same time, the ultrasonic generator and the pulsed magnetic field generator are turned on. Then, the freeze-drying protectant, antioxidant and metal ion chelating agent are added in batches. The mixture is stirred at 150 rpm for 3 minutes at room temperature. The pre-mixed mixture of folic acid, vitamin B6, biotin, riboflavin sodium phosphate, vitamin B12, thiamine nitrate, sodium pantothenate, nicotinamide and sodium vitamin C is stirred at 150 rpm for 3 minutes at room temperature. Finally, the pH of the system is adjusted to 5.5 with a pH adjuster (specifically, a 0.6% sodium hydroxide solution). The water for injection is added to the full volume and stirred at 150 rpm for 3 minutes at room temperature to obtain the drug solution. The ratio Y of the ultrasonic frequency F2 and the pulsed magnetic field frequency F1 is 4 × 10. 3 Specifically: the pulse magnetic field frequency is 15Hz, the pulse magnetic field voltage is 80V, the ultrasonic frequency is 60kHz, and the ultrasonic power is 165W.

[0101] Comparative Example 2

[0102] This example provides a water-soluble vitamin preparation for injection and its preparation method, which differs from Example 1 only in that:

[0103] (1) In the solution preparation process, the pulsed magnetic field-ultrasound coupling treatment is replaced with ultrasound treatment only. The specific process is as follows: folic acid, biotin, thiamine nitrate and vitamin B12 are mixed to obtain the first vitamin mixture; vitamin B6, nicotinamide, sodium vitamin C, sodium riboflavin phosphate and sodium pantothenate are mixed to obtain the second vitamin mixture; under a nitrogen atmosphere, 80 vol% of the total volume of water for injection is added to the container and an ultrasonic vibrator is inserted at the center of the container; the ultrasonic generator is turned on, and then the freeze-drying protectant, antioxidant and metal are added in batches. The ion chelating agent was stirred at 150 rpm for 3 minutes at room temperature. The first vitamin mixture was stirred at 150 rpm for 3 minutes at room temperature. The second vitamin mixture was stirred at 150 rpm for 3 minutes at room temperature. Finally, the pH of the system was adjusted to 5.5 with a pH adjuster (specifically, a 0.6% sodium hydroxide solution). After adding water for injection to the full volume, the mixture was stirred at 150 rpm for 3 minutes at room temperature to obtain the drug solution. The ultrasonic frequency was 60 kHz and the ultrasonic power was 165 W.

[0104] Comparative Example 3

[0105] This example provides a water-soluble vitamin preparation for injection and its preparation method, which differs from Example 1 only in that:

[0106] (1) The ratio Y of the ultrasonic frequency F2 and the pulse magnetic field frequency F1 during the solution preparation process is 4 × 10⁻⁶. 4 Specifically, the operating conditions of the pulsed magnetic field-ultrasound composite field include: the pulsed magnetic field frequency is 1.5Hz, the pulsed magnetic field voltage is 80V, the ultrasonic frequency is 60kHz, and the ultrasonic power is 165W.

[0107] Test Example 1

[0108] This test example examines the water-soluble vitamin preparations for injection obtained in Examples 1-3 and Comparative Examples 1-3 above under conditions of 25℃±2℃ and RH60%±5% for 12 months. The test results are shown in Table 1.

[0109] Table 1. Changes in the content of each vitamin in water-soluble vitamin preparations for injection after 12 months of long-term stability testing.

[0110]

[0111] As shown in Table 1, this invention mainly achieves room temperature operation throughout the entire solution preparation process by constructing a graded feeding system based on the relative differences in vitamin water solubility and utilizing the synergistic effect of a pulsed magnetic field-ultrasound composite field at an appropriate frequency. This eliminates the need for additional solubilizers and heating, resulting in minimal temperature fluctuations during the solution preparation process. This improves the stability of the obtained vitamin preparation and the efficiency of the preparation process, providing a new technical means for the preparation of water-soluble vitamin preparations for injection. Furthermore, the appearance morphology and accelerated testing results of the obtained water-soluble vitamin preparations for injection meet the requirements.

[0112] Various embodiments of the present invention may exist in the form of a range; it should be understood that the description in the form of a range is merely for convenience and brevity and should not be construed as a hard limitation on the scope of the invention; therefore, it should be considered that the range description has specifically disclosed all possible subranges and single numerical values ​​within that range. For example, it should be considered that the range description from 1 to 6 has specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and single numbers within the range, such as 1, 2, 3, 4, 5, and 6, regardless of the range. Furthermore, whenever a numerical range is referred to herein, it means including any referenced number (fraction or integer) within the range referred to.

[0113] The above description is merely a specific embodiment of the present invention, enabling those skilled in the art to understand or implement the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the present invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features claimed herein.

Claims

1. A method for preparing a water-soluble vitamin preparation for injection, characterized by, The preparation method of the water-soluble vitamin preparation for injection comprises the following steps: weighing raw materials, preparing a solution, sterilizing and filtering, filling, freeze-drying, pressing a plug and capping. The solution preparation comprises the following steps: mixing folic acid, biotin, thiamine nitrate and vitamin B12 to obtain a first vitamin mixture; mixing vitamin B6, nicotinamide, vitamin C sodium, riboflavin sodium phosphate and pantothenic acid sodium to obtain a second vitamin mixture; under the action of a pulsed magnetic field-ultrasonic wave compound field and an inert gas atmosphere, the freeze-drying protective agent, the antioxidant, the metal ion chelating agent, the first vitamin mixture and the second vitamin mixture are added into water for injection in batches and stirred at room temperature, then a pH regulator is used to adjust the pH of the system to 5.3-5.8 and supplement water for injection to the full amount to obtain a medicinal solution; wherein the ratio Y of the ultrasonic frequency F2 and the pulsed magnetic field frequency F1 ranges from 2 x 10 3 -6 x 10 3 ; the working condition parameters of the pulsed magnetic field-ultrasonic wave compound field include that the frequency of the pulsed magnetic field is 10-20 Hz, the voltage of the pulsed magnetic field is 70-100 V, the frequency of the ultrasonic wave is 40-60 kHz and the power of the ultrasonic wave is 100-200 W; the dosage of the folic acid added is 0.38-0.42 mg in 3 ml of water for injection; the dosage of the vitamin B6 added is 4.8-5.0 mg in 3 ml of water for injection; the dosage of the biotin added is 58-62 μg in 3 ml of water for injection; the dosage of the riboflavin sodium phosphate added is 4.8-5.0 mg in 3 ml of water for injection; the dosage of the vitamin B12 added is 4.8-5.2 μg in 3 ml of water for injection; the dosage of the thiamine nitrate added is 2.8-3.2 mg in 3 ml of water for injection; the dosage of the pantothenic acid sodium added is 16.0-17.0 mg in 3 ml of water for injection; the dosage of the nicotinamide added is 39.0-41.0 mg in 3 ml of water for injection; the dosage of the vitamin C sodium added is 111-115 mg in 3 ml of water for injection; the dosage of the freeze-drying protective agent added is 295-305 mg in 3 ml of water for injection; the dosage of the metal ion chelating agent added is 490-505 μg in 3 ml of water for injection; the dosage of the antioxidant added is 3.5-4.0 mg in 3 ml of water for injection.

2. The method for preparing a water-soluble vitamin preparation for injection according to claim 1, characterized by, The Y is 4 x 10 3 .

3. The method for preparing a water-soluble vitamin preparation for injection according to claim 1, characterized by, The working condition parameters of the pulsed magnetic field-ultrasonic wave compound field include that the frequency of the pulsed magnetic field is 15 Hz, the voltage of the pulsed magnetic field is 80 V, the frequency of the ultrasonic wave is 60 kHz and the power of the ultrasonic wave is 165 W.

4. The method for preparing a water-soluble vitamin preparation for injection according to any one of claims 1 to 3, characterized by, under the action of a pulsed magnetic field-ultrasonic wave compound field and an inert gas atmosphere, the freeze-drying protective agent, the antioxidant, the metal ion chelating agent, the first vitamin mixture and the second vitamin mixture are added into water for injection in batches and stirred at room temperature, then a pH regulator is used to adjust the pH of the system to 5.3-5.8 and supplement water for injection to the full amount to obtain a medicinal solution adding 75~85 vol% of injection water to a container under inert gas atmosphere and inserting an ultrasonic vibration rod at the center of the container, then applying a pulsed magnetic field outside the container; simultaneously starting the ultrasonic wave generator and the pulsed magnetic field generator, then adding the freeze-drying protective agent, the antioxidant and the metal ion chelating agent in batches, respectively, stirring for 2~5 min at room temperature, stirring the first vitamin mixture for 2~5 min at room temperature, stirring the second vitamin mixture for 2~5 min at room temperature, and finally adjusting the pH of the system to 5.3~5.8 with a pH adjuster and adding injection water to the full amount, then stirring for 2~5 min at room temperature to obtain the injection solution.

5. The method for preparing a water-soluble vitamin preparation for injection according to claim 1, characterized by, The dosage of folic acid is 0.4 mg based on 3 ml of injection water; The dosage of vitamin B6 is 4.9 mg based on 3 ml of injection water; The dosage of biotin is 60 μg based on 3 ml of injection water; The dosage of riboflavin sodium phosphate is 4.9 mg based on 3 ml of injection water; The dosage of vitamin B12 is 5.0 μg based on 3 ml of injection water; The dosage of thiamine mononitrate is 3.1 mg based on 3 ml of injection water; The dosage of sodium pantothenate is 16.5 mg based on 3 ml of injection water; The dosage of nicotinamide is 40.0 mg based on 3 ml of injection water; The dosage of vitamin C sodium is 113.0 mg based on 3 ml of injection water; The dosage of the freeze-drying protective agent is 300.0 mg based on 3 ml of injection water; The dosage of the metal ion chelating agent is 500.0 μg based on 3 ml of injection water; The dosage of the antioxidant is 3.8 mg based on 3 ml of injection water.

6. The method for preparing a water-soluble vitamin preparation for injection according to any one of claims 1 to 3, characterized by, The freeze-drying protective agent includes glycine, the metal ion chelating agent includes edetate disodium, the antioxidant includes sodium bisulfite, and the pH adjuster includes a sodium hydroxide solution with a mass fraction of 0.5~0.8%.

7. The method for preparing a water-soluble vitamin preparation for injection according to any one of claims 1 to 3, characterized by, The step of freeze-drying includes the following processes: When the temperature of the freeze-drying device is reduced to -8℃~-5℃, the injection solution is placed in the device and kept for 30 min~60 min, the temperature is reduced to -20℃~-10℃ at a rate of 20℃ / min~25℃ / min and kept for 1.5 h~2.5 h, then the temperature is reduced to -45℃~-40℃ at a rate of 10℃ / min~15℃ / min and kept for 2.5 h~3.5 h, the vacuum degree is reduced to below 0.1 Mbar, and the temperature is increased to 20℃~22℃ at a rate of 1~5℃ / min and kept for 4 h~5 h.

8. A water-soluble vitamin preparation for injection, characterized by, The injection water-soluble vitamin preparation is prepared by the method of any one of claims 1~7.

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