Vitamin C injection and preparation method thereof

Abstract

The invention discloses a vitamin C injection and a preparation method thereof. The preparation method of the vitamin C injection comprises the following steps: taking water for injection, which accounts for 65-80% of the total volume of the prepared solution, and introducing carbon dioxide until the water is saturated, so as to obtain a saturated solution of carbon dioxide; the preparation method comprises the following steps: adding sodium pyrosulfite, edetate disodium and cysteine hydrochloride into a saturated solution of carbon dioxide, and stirring to fully dissolve the sodium pyrosulfite, the edetate disodium and the cysteine hydrochloride to obtain a first liquid medicine; uniformly mixing vitamin C and sodium bicarbonate to obtain mixed powder, and adding the mixed powder into the first liquid medicine in batches to obtain second liquid medicine; adding activated carbon into the second liquid medicine, stirring and then filtering, replenishing the residual 20-35% of water for injection, and then finely filtering; and packaging and warehousing the finely filtered liquid medicine after encapsulation, sterilization, leak detection and light inspection. The vitamin C injection prepared by the invention is colorless and clear, the content of effective components is as high as 99.6%, and the impurity content is extremely low.

Description

Technical Field

[0001] The invention belongs to the pharmaceutical field, and in particular relates to a vitamin C injection and a preparation method thereof. Background Art

[0002] Vitamin C (ascorbic acid) participates in a variety of biochemical processes in the body, including amino acid metabolism, neurotransmitter synthesis, collagen and tissue cell matrix formation, helps maintain vascular integrity, promotes the absorption of non-heme iron, and maintains the normal function of the immune system and increases resistance to infection. In addition, vitamin C is also involved in the detoxification process, has an antihistamine effect, and can prevent the formation of carcinogens such as nitrosamines.

[0003] At present, vitamin C injection is mainly used to treat various diseases caused by vitamin C deficiency, such as scurvy or chronic iron poisoning. It is also often used as an adjuvant treatment for acute and chronic infectious diseases. Vitamin C supplementation is necessary for patients who have strict dietary control or receive parenteral nutrition. In addition, pregnant and lactating women can also use vitamin C injection to supplement the required nutrition.

[0004] There are many advantages to making vitamin C into an injection: 1. Rapid efficacy: Directly injected into human tissues, blood vessels or organs in liquid form, it is quickly absorbed, has high bioavailability, accurate dosage and reliable effect. 2. Suitable for special patients: Suitable for patients who cannot take oral medication, such as patients in a coma, convulsion or spasm, or patients with digestive system disorders. 3. Stability and preservation: Since the injection is sealed in a special container, isolated from the outside air, and sterilized or aseptically operated during the manufacturing process, it is more durable than other liquid preparations and can effectively prevent the oxidation and deterioration of vitamin C.

[0005] However, the existing production process of vitamin C injection still has the following problems: 1. pH instability: Despite the adoption of various measures, the pH value of the product may still fluctuate in some cases, affecting the stability of the drug. 2. Oxidation reaction during storage: Even if the product is sealed and sterilized, vitamin C may still react with trace oxygen or container materials during storage, resulting in color changes (such as yellowing) and reduced activity. Summary of the invention

[0006] In view of the shortcomings of the prior art, the object of the present invention is to provide a vitamin C injection and a preparation method thereof.

[0007] The purpose of the present invention is achieved through the following technical solutions: A method for preparing vitamin C injection comprises the following steps: (1) Take 65-80% of the total volume of the injection water and introduce carbon dioxide into it until it is saturated to obtain a saturated solution of carbon dioxide; (2) adding sodium pyrosulfite, disodium edetate and cysteine ​​hydrochloride to the saturated solution of carbon dioxide in step (1), stirring to fully dissolve them, and obtaining a first liquid medicine; mixing vitamin C and sodium bicarbonate uniformly to obtain a mixed powder, and adding the mixed powder to the first liquid medicine in batches to obtain a second liquid medicine after the addition is complete; (3) Adding activated carbon to the second liquid medicine in step (2), stirring, filtering, adding the remaining 20-35% of water for injection, and then fine filtering; the finely filtered liquid medicine is packaged and put into storage after filling, sterilization, leak detection, and light inspection.

[0008] Preferably, the dosage ratio of vitamin C, sodium bicarbonate, sodium metabisulfite, disodium edetate, cysteine ​​hydrochloride and water for injection is 100g:80-90g:3-4g:1-2g:0.2-0.8g:2000mL.

[0009] Preferably, in step (2), sodium metabisulfite, disodium edetate and cysteine ​​hydrochloride are added to a saturated solution of carbon dioxide and stirred at a rate of 100-500 rpm for 15-30 min.

[0010] Preferably, in step (2), the mixed powder is added to the first liquid medicine in 3 to 5 batches.

[0011] Preferably, in step (3), the activated carbon is injection activated carbon.

[0012] Preferably, in step (3), the volume ratio of the activated carbon to the water for injection is 0.1-0.05% (w / v, g / mL).

[0013] Preferably, in step (3), the stirring time is 5 to 10 minutes.

[0014] Preferably, in step (3), the filtering operation process is as follows: first filter with a microporous membrane with a pore size of 0.45 μm, and then filter the obtained filtrate through a microporous membrane with a pore size of 0.22 μm.

[0015] Preferably, in step (3), the fine filtration operation process is as follows: a microporous membrane with a pore size of 0.22 μm is used for three-stage filtration.

[0016] Preferably, in step (3), the remaining 20-35% of the water for injection is water for injection that has been saturated with carbon dioxide.

[0017] The vitamin C injection prepared by the above-mentioned method for preparing the vitamin C injection.

[0018] Compared with the prior art, the beneficial effects of the present invention include: In the present invention, vitamin C and sodium bicarbonate are mixed uniformly before adding the remaining raw material components. In some cases (for example, vitamin C has reached the saturation point or is close to the saturation point in water, then adding sodium bicarbonate can further promote the dissolution of undissolved vitamin C by changing the local pH value), sodium bicarbonate helps to improve the solubility of vitamin C and ensure that the drug can be fully dissolved in the solvent to form a uniform solution, which is very important for ensuring the accuracy of the drug dosage. In addition, pre-mixing can avoid the crystallization or precipitation of vitamin C caused by local oversaturation, thereby ensuring the physical stability of the final product. DETAILED DESCRIPTION

[0019] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0020] Example 1 A method for preparing vitamin C injection, the specific steps are as follows: (1) Take 80% of the total volume of the injection water, i.e. 1600 mL of injection water, and pass carbon dioxide into it until saturated to obtain a saturated solution of carbon dioxide; (2) Adding 4 g of sodium pyrosulfite, 2 g of disodium edetate and 0.5 g of cysteine ​​hydrochloride to the saturated solution of carbon dioxide in step (1), stirring at a rate of 500 rpm for 15 min to fully dissolve them, to obtain a first liquid; mixing 100 g of vitamin C and 80 g of sodium bicarbonate evenly to obtain a mixed powder, adding the mixed powder to the first liquid in three batches, and obtaining a second liquid after the addition is complete; (3) Add 5 g of activated carbon to the second liquid medicine in step (2), stir for 5 min and then filter. The specific operation is as follows: The filtering operation process is as follows: first filter with a microporous membrane with a pore size of 0.45 μm. Then filter the obtained filtrate through a microporous membrane with a pore size of 0.22 μm; after filtration, add the remaining 20% ​​of injection water (i.e. 400 mL injection water) and then perform fine filtration. The fine filtration operation process is as follows: use a microporous membrane with a pore size of 0.22 μm for three-stage filtration; the finely filtered liquid medicine is packaged and stored after potting, sterilization, leak detection, and light inspection.

[0021] Example 2 A method for preparing vitamin C injection, the specific steps are as follows: (1) Take 70% of the total volume of the injection water, i.e. 1400 mL of injection water, and pass carbon dioxide into it until saturated to obtain a saturated solution of carbon dioxide; (2) adding 3 g of sodium pyrosulfite, 1 g of disodium edetate and 0.4 g of cysteine ​​hydrochloride to the saturated solution of carbon dioxide in step (1), stirring at a rate of 500 rpm for 15 min to fully dissolve them, to obtain a first liquid; mixing 100 g of vitamin C and 85 g of sodium bicarbonate evenly to obtain a mixed powder, adding the mixed powder to the first liquid in three batches, and obtaining a second liquid after the addition is complete; (3) Add 3 g of activated carbon to the second liquid medicine in step (2), stir for 5 min and then filter. The specific operation is as follows: The filtering operation process is as follows: first filter with a microporous membrane with a pore size of 0.45 μm. Then filter the obtained filtrate through a microporous membrane with a pore size of 0.22 μm; after filtration, add the remaining 30% of injection water (i.e., 600 mL injection water) and then perform fine filtration. The fine filtration operation process is as follows: use a microporous membrane with a pore size of 0.22 μm for three-stage filtration; the finely filtered liquid medicine is packaged and stored after potting, sterilization, leak detection, and light inspection.

[0022] Example 3 A method for preparing vitamin C injection, the specific steps are as follows: (1) Take 65% of the total volume of the injection water, i.e. 1300 mL of injection water, and pass carbon dioxide into it until saturated to obtain a saturated solution of carbon dioxide; (2) Adding 4 g of sodium pyrosulfite, 2 g of disodium edetate and 0.8 g of cysteine ​​hydrochloride to the saturated solution of carbon dioxide in step (1), stirring at a rate of 500 rpm for 15 min to fully dissolve them, to obtain a first liquid; mixing 100 g of vitamin C and 90 g of sodium bicarbonate evenly to obtain a mixed powder, adding the mixed powder to the first liquid in three batches, and obtaining a second liquid after the addition is complete; (3) Add 5 g of activated carbon to the second liquid medicine in step (2), stir for 5 min and then filter. The specific operation is as follows: The filtering operation process is as follows: first filter with a microporous membrane with a pore size of 0.45 μm. Then filter the obtained filtrate through a microporous membrane with a pore size of 0.22 μm; after filtration, add the remaining 20% ​​of injection water (i.e. 700 mL injection water) and then perform fine filtration. The fine filtration operation process is as follows: use a microporous membrane with a pore size of 0.22 μm for three-stage filtration; the finely filtered liquid medicine is packaged and stored after potting, sterilization, leak detection, and light inspection.

[0023] Example 4 A method for preparing vitamin C injection, the specific steps are as follows: (1) Take 80% of the total volume of the injection water, i.e. 1600 mL of injection water, and pass carbon dioxide into it until saturated to obtain a saturated solution of carbon dioxide; (2) Adding 4 g of sodium pyrosulfite, 2 g of disodium edetate and 0.5 g of cysteine ​​hydrochloride to the saturated solution of carbon dioxide in step (1), stirring at a rate of 500 rpm for 15 min to fully dissolve them, to obtain a first liquid; mixing 100 g of vitamin C and 80 g of sodium bicarbonate evenly to obtain a mixed powder, adding the mixed powder to the first liquid in three batches, and obtaining a second liquid after the addition is complete; (3) Add 5 g of activated carbon to the second liquid medicine in step (2), stir for 5 min and then filter. The specific operation is as follows: The filtering operation process is as follows: first filter with a microporous membrane with a pore size of 0.45 μm. Then filter the obtained filtrate through a microporous membrane with a pore size of 0.22 μm; after filtration, add the remaining 20% ​​of injection water (i.e. 400 mL injection water) and then perform fine filtration. The fine filtration operation process is as follows: use a microporous membrane with a pore size of 0.22 μm for three-stage filtration; the finely filtered liquid medicine is packaged and stored after potting, sterilization, leak detection, and light inspection.

[0024] Comparative Example 1 A method for preparing vitamin C injection, the specific steps are as follows: (1) Take 80% of the total volume of the injection water, i.e. 1600 mL of injection water, and pass carbon dioxide into it until saturated to obtain a saturated solution of carbon dioxide; (2) Add 100 g of vitamin C to the saturated solution of carbon dioxide in step (1), then add 80 g of sodium bicarbonate in three batches, and stir continuously until completely dissolved. Then, add 4 g of sodium pyrosulfite, 2 g of disodium edetate and 0.5 g of cysteine ​​hydrochloride, and stir at a rate of 500 rpm for 15 min to fully dissolve them, to obtain a drug solution; (3) Add 5g of activated carbon to the liquid medicine in step (2), stir for 5min and then filter. The specific operation is as follows: The filtering operation process is as follows: first filter with a microporous membrane with a pore size of 0.45μm. Then filter the obtained filtrate through a microporous membrane with a pore size of 0.22μm; after filtration, add the remaining 20% ​​of injection water (i.e. 400mL injection water) and then perform fine filtration. The fine filtration operation process is as follows: use a microporous membrane with a pore size of 0.22μm for three-stage filtration; the liquid medicine after fine filtration is packaged and stored after filling, sterilization, leak detection, and light inspection.

[0025] The vitamin C injections prepared in Examples 1 to 3 and Comparative Example 1 were tested for various indicators. Ten samples were taken from each Example or Comparative Example. The test results are shown in Table 1.

[0026] Table 1 Test results of various indicators

[0027] Note: VC content and pH value of 10 samples were tested respectively, and the average value of these samples was taken as the final test result.

[0028] According to the data in Table 1, it can be seen that the vitamin C injection obtained by the preparation method of the present invention is colorless and clear, with an effective ingredient content of up to 99.6% and extremely low impurity content. In contrast, the vitamin C injection prepared in Comparative Example 1 has a slightly yellowish appearance and a VC content slightly lower than that of the present invention.

[0029] The specific implementation of the present invention does not constitute a limitation on the protection scope of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A method for preparing vitamin C injection, characterized in that: The steps include: (1) Take 65-80% of the total volume of the injection water and introduce carbon dioxide into it until it is saturated to obtain a saturated solution of carbon dioxide; (2) adding sodium pyrosulfite, disodium edetate and cysteine ​​hydrochloride to the saturated solution of carbon dioxide in step (1), stirring to fully dissolve them, and obtaining a first liquid medicine; mixing vitamin C and sodium bicarbonate evenly to obtain a mixed powder, and adding the mixed powder to the first liquid medicine in batches to obtain a second liquid medicine; (3) Adding activated carbon to the second drug solution in step (2), stirring, filtering, adding the remaining 20-35% of water for injection, and then fine filtering; the finely filtered drug solution is packaged and stored after filling, sterilization, leak detection, and light inspection.

2. The method for preparing the vitamin C injection according to claim 1, characterized in that: The dosage ratio of the vitamin C, sodium bicarbonate, sodium pyrosulfite, disodium edetate, cysteine ​​hydrochloride and water for injection is 100g: 80-90g: 3-4g: 1-2g: 0.2-0.8g: 2000mL.

3. The method for preparing the vitamin C injection according to claim 2, characterized in that: The sodium pyrosulfite, disodium edetate and cysteine ​​hydrochloride in step (2) are added to a saturated solution of carbon dioxide and stirred at a rate of 100-500 rpm for 15-30 min.

4. The method for preparing the vitamin C injection according to claim 1, characterized in that: Step (2) adding the mixed powder into the first liquid medicine in 3 to 5 batches; The activated carbon in step (3) is activated carbon for injection.

5. The method for preparing the vitamin C injection according to claim 4, characterized in that: The volume ratio of the activated carbon to the water for injection in step (3) is 0.1-0.05%.

6. The method for preparing the vitamin C injection according to claim 1, characterized in that: The stirring time in step (3) is 5 to 10 minutes.

7. The method for preparing the vitamin C injection according to claim 1, characterized in that: The filtering operation process of step (3) is as follows: first filter with a microporous membrane with a pore size of 0.45 μm, and then filter the obtained filtrate through a microporous membrane with a pore size of 0.22 μm.

8. The method for preparing the vitamin C injection according to claim 7, characterized in that: The operation process of the fine filtration in step (3) is as follows: a microporous membrane with a pore size of 0.22 μm is used for three-stage filtration.

9. The method for preparing the vitamin C injection according to claim 1, characterized in that: The remaining 20-35% of the water for injection in step (3) is water for injection that has been saturated with carbon dioxide.

10. The vitamin C injection prepared by the method for preparing the vitamin C injection according to any one of claims 1 to 9.

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