Iomeprol injection and a preparation method thereof

Abstract

The present application relates to the technical field of pharmaceutical preparation, in particular to a iomeprol injection and a preparation method thereof.The iomeprol injection provided by the present application comprises iomeprol, sodium citrate, a pH regulator and water for injection.The iomeprol injection prepared by the present application has high safety, good stability and low viscosity.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, and in particular to an iodine-methyl injection and its preparation method. Background Technology

[0002] Iomeprazole is a non-ionic iodine contrast agent used in intravenous urography, computed tomography, routine angiography, digital subtraction angiography, cardiovascular angiography, routine selective coronary angiography, interventional coronary angiography, fistula angiography, ductography, dacryocystorhinostomy, and sialocystography. Its structural formula is as follows:

[0003] .

[0004] Iomeprazole, synthesized by Bracco in Italy, was first approved as an injectable form in the UK in 1992, and subsequently approved in Italy, Japan, France, Germany, Spain, and other countries. According to the 2020 expert consensus, iodazole (iodine concentration 400 mg / ml) is recommended for use in liver CT (computed tomography) scans, demonstrating its clear clinical value. Iomeprazole is available in various raw material concentrations on the market, but the most commonly used clinical concentration is as high as 81.65% (w / w), equivalent to an iodine concentration of 400 mg / ml. The excipients include 1 mg / mL tromethorphan, hydrochloric acid for pH adjustment, and water for injection.

[0005] However, from the perspective of the clinical application of iodine-methyl, the following problems still exist: (1) As an iodine contrast agent, iodine-methyl can provide a larger iodine flow rate for the same volume of drug solution compared with the same type of iodine contrast agent, but the viscosity is greater and the irritation is slightly greater; (2) The prescription contains other pharmacologically active substances: tromethorphan, which has pharmacological activity, is used as a pH buffer, and its side effects cannot be ignored. It can cause hypoglycemia, hypotension, nausea, vomiting, and in severe cases, it can also inhibit respiration or even cause respiratory arrest; (3) Narrow pH range: The standard pH range of the finished injection solution is 6.5 to 7.2, and the pH value decreases during the long-term stability process, resulting in a smaller adjustable range during production, which is not conducive to large-scale industrial production. Therefore, there is an urgent need for an iodine-methyl injection solution with high stability, high safety, and conducive to large-scale industrial production. Summary of the Invention

[0006] To address the side effects of tromethorphan in iodide injection, the inventors attempted to replace tromethorphan with various pH buffers, including sodium acetate, potassium dihydrogen phosphate, and sodium tartrate. However, the results were unsatisfactory, with unstable pH and excessively high iodide content. See Comparative Examples 1 to 3 for details.

[0007] During the research, the inventors discovered that the commercially available iodine-1 injection (hereinafter referred to as the original formulation) also has problems such as being relatively sensitive to metal ions, which leads to an increase in impurities in the iodine-1 injection (see Comparative Examples 4 to 6). After adding the chelating agent calcium edetate, the stability of the iodine-1 injection is improved, but there is a risk that sodium edetate can combine with calcium ions to form a soluble complex, causing a decrease in blood calcium concentration.

[0008] However, the inventors accidentally discovered that using sodium citrate not only solved the problems of stability and safety, but also produced an iodine sorbitol injection with low viscosity, which could improve patient compliance during clinical use.

[0009] Therefore, in order to solve the above-mentioned problems, the present invention proposes to adopt the following technical solution:

[0010] An iodomeprazole injection solution includes iodomeprazole, sodium citrate, a pH adjuster, and water for injection.

[0011] Furthermore, the mass ratio of iodomeprazole to sodium citrate is 60~90:0.1~3, preferably 60~85:0.1~2.0.

[0012] Furthermore, the volume of the water for injection is 40% to 95% of that of iodine-methyl injection, preferably 50% to 90%.

[0013] In some specific embodiments of the present invention, each 100 mL injection solution comprises: 81.65 g iodine-methyl and 0.2 g sodium citrate.

[0014] In this invention, the pH adjustment is achieved using pH adjusters conventionally used in the art, which can be either acids or bases. Those skilled in the art can select the specific amount of pH adjuster based on the type of pH adjuster chosen, as long as the pH value of the iodine-methyl injection is between 5.0 and 7.0.

[0015] Furthermore, the pH adjuster is selected from citric acid, phosphoric acid, hydrochloric acid, acetic acid, tartaric acid, and preferably citric acid.

[0016] In this invention, the viscosity of the iodine-methyl injection is less than 28 mPa·s; at a temperature of 20°C, the viscosity of the iodine-methyl injection is 20~28 mPa·s, further, the viscosity is 27.3 mPa·s; at a temperature of 37°C, the viscosity of the iodine-methyl injection is 10~15 mPa·s, further, the viscosity is 14.8 mPa·s; at a temperature of 50°C, the viscosity of the iodine-methyl injection is 5~9 mPa·s, further, the viscosity is 8.4 mPa·s.

[0017] Currently, the viscosity of iodine-methyl injection on the market is 10~30 mPa·s; at a temperature of 20℃, the viscosity of iodine-methyl injection is 28.5 mPa·s; at a temperature of 37℃, the viscosity of iodine-methyl injection is 16.9 mPa·s; and at a temperature of 50℃, the viscosity of iodine-methyl injection is 10.2 mPa·s.

[0018] The iodine-methyl injection prepared by this invention has low viscosity, which improves patient compliance in clinical use.

[0019] This invention also provides a method for preparing iodine sorbitol injection, comprising the following steps:

[0020] (1) Dissolve sodium citrate and adjust the pH;

[0021] (2) Add iodine sorbitol, stir to dissolve, and adjust the pH;

[0022] (3) Filtration and filling;

[0023] (4) Sterilization and packaging.

[0024] Further, in step (1), the pH is adjusted to 7.0 to 8.5, preferably 7.5 to 8.0.

[0025] Further, in step (2), the pH is adjusted to 4.5 to 7.5, preferably 5.0 to 7.0.

[0026] Furthermore, the temperature in step (1) is 50~100℃, preferably 60~90℃.

[0027] In this invention, the sterilization method can be selected from, but is not limited to, dry heat sterilization, filtration sterilization, boiling sterilization, flowing steam sterilization, autoclaving sterilization, low-temperature intermittent sterilization, gamma-ray radiation sterilization, ultraviolet sterilization, microwave sterilization, gas sterilization, chemical agent sterilization, etc.

[0028] The beneficial effects of this invention are as follows:

[0029] (1) High safety: The present invention uses sodium citrate as a pH buffer to avoid the toxic side effects of tromethorphan. For some patients, such as those with chronic respiratory acidosis and renal acidosis, injections containing tromethorphan are contraindicated. The iodomeprazole injection of the present invention broadens the user population. At the same time, it avoids the use of conventional chelating agents such as disodium edetate or calcium edetate, thus avoiding the side effect of decreased blood calcium.

[0030] (2) Strong stability: The combination of sodium citrate and citric acid used in this invention has a strong pH buffering capacity, which can ensure the long-term stability of the product quality; the buffering system broadens the adjustable pH range when the drug solution is stable, making it easier to control during production, reducing the risk of the entire batch being scrapped due to solution failure, saving costs, and being more conducive to large-scale industrial production.

[0031] (3) Low viscosity: The iodine-methyl injection prepared by this invention has low viscosity, which improves the compliance of clinical patients. Detailed Implementation

[0032] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to comparative examples and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. Furthermore, unless otherwise specified, all reagents used in the following embodiments are commercially available or can be synthesized according to methods described herein or known to the public. Reaction conditions not listed are also readily available to those skilled in the art.

[0033] 1. This invention research involved commercially available iodide-1 injection (Dianmailun). ® (hereinafter referred to as the original formulation), its formula is shown in Table 1:

[0034]

[0035] 2. The present invention relates to analytical detection methods as follows:

[0036] (1) Properties: According to the pharmacopoeia, the color of the drug solution is compared with the specified standard colorimetric solution.

[0037] (2) Absorbance: Take this product and measure it at a wavelength of 450 nm using the ultraviolet-visible spectrophotometric method (Chinese Pharmacopoeia 2020 edition) with a 4 cm cuvette. The absorbance shall not exceed 0.060.

[0038] (3) Inorganic iodides: Accurately measure 20 mL of this product, add 20–30 mL of acetate-sodium acetate buffer (pH 4.6), and mix well. Titrate with silver nitrate titrant (0.001 mol / L) according to the potentiometric titration method (Chinese Pharmacopoeia 2020 edition). Each 1 mL of silver nitrate titrant (0.001 mol / L) is equivalent to 0.1269 mg of I. The inorganic iodides contained in this product per 100 mL, calculated as iodine (I), shall not exceed 4.0 mg.

[0039] (4) Content determination: determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 edition, Part IV, General Chapter 0512).

[0040] Solvent: Acetonitrile-2-butanol-water (85:10:60).

[0041] Test solution: Accurately measure an appropriate amount of this product and dilute it with water to prepare a solution containing approximately 0.5 mg of iodine methimazole per 1 ml.

[0042] Reference solution: Weigh an appropriate amount of iodine methylprednisolone reference standard accurately, dissolve and dilute it with water to prepare a solution containing approximately 0.5 mg per ml.

[0043] Chromatographic conditions: Octadecylsilane-bonded silica gel was used as the stationary phase (ChromCore AQ-C18, 4.6 mm × 100 mm, 5 μm or equivalent column); 0.0125 mol / L potassium dihydrogen phosphate-solvent (97:3) was used as mobile phase A, and acetonitrile was used as mobile phase B, with gradient elution according to Table 2; flow rate was 1.0 mL per minute; column temperature was 60 °C; detection wavelength was 245 nm; injection volume was 10 μL.

[0044]

[0045] Determination method: Accurately measure the test solution and the reference solution, inject them separately into the liquid chromatograph, record the chromatograms, and calculate the result by peak area according to the external standard method.

[0046] Example 1

[0047] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of sodium citrate and stir until completely dissolved, then add citric acid to adjust the pH to 6.5; then add 81.65 g of iodine sorbitol in portions, stirring to dissolve, and keep warm for 10 min, then adjust the pH of the solution to 6.0 with citric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill the container; finally, sterilize at 121°C for 15 min. Example

[0048] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of sodium citrate and stir until completely dissolved, then add citric acid to adjust the pH to 7.5–8.0; then add 81.65 g of iodine sorbitol in portions, stirring to dissolve and keeping warm for 10 min, then adjust the pH of the solution to 5.0–7.0 with citric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill into the container; finally, sterilize. Example

[0049] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of sodium citrate and stir until completely dissolved, then add citric acid to adjust the pH to 7.5–8.0; then add 81.65 g of iodine methylphenidate in portions, stirring to dissolve and keeping warm for 10 min, then add approximately 60 ng / mL of copper sulfate aqueous solution, and then adjust the pH of the solution to 5.0–7.0 with citric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill into the container; finally, sterilize. Example

[0050] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of sodium citrate and stir until completely dissolved, then add citric acid to adjust the pH to 7.5–8.0; then add 81.65 g of iodine sorbitol in portions, stirring to dissolve and keeping warm for 10 min, then adjust the pH of the solution to 7.5 with citric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill into the container; finally, sterilize. Example

[0051] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of sodium citrate and stir until completely dissolved, then add citric acid to adjust the pH to 7.5–8.0; then add 81.65 g of iodine sorbitol in portions, stirring to dissolve and keeping warm for 10 min, then adjust the pH of the solution to 7.0 with citric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill into the container; finally, sterilize. Example

[0052] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of sodium citrate and stir until completely dissolved, then add citric acid to adjust the pH to 7.5–8.0; then add 81.65 g of iodine sorbitol in portions, stirring to dissolve, and keep warm for 10 min. Then adjust the pH of the solution to 6.5 with citric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, and then filter through a 0.22 μm sterile filter cartridge before filling; finally, sterilize. Example

[0053] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of sodium citrate and stir until completely dissolved, then add citric acid to adjust the pH to 7.5–8.0; then add 81.65 g of iodine sorbitol in portions, stirring to dissolve and keeping warm for 10 min, then adjust the pH of the solution to 6.0 with citric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill into the container; finally, sterilize. Example

[0054] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of sodium citrate and stir until completely dissolved, then add citric acid to adjust the pH to 7.5–8.0; then add 81.65 g of iodine sorbitol in portions, stirring to dissolve and keeping warm for 10 min, then adjust the pH of the solution to 5.5 with citric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill into the container; finally, sterilize. Example

[0055] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of sodium citrate and stir until completely dissolved, then add citric acid to adjust the pH to 7.5–8.0; then add 81.65 g of iodine-methyl in portions, stirring to dissolve and keeping warm for 10 min, then adjust the pH of the solution to 5.0 with citric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill into the container; finally, sterilize.

[0056] The sterilized samples from Examples 4 to 9 were sent for testing of the following indicators, and the comparative results are shown in Table 3.

[0057]

[0058] As shown in Table 3, according to the formulation and process of this invention, accelerated sampling and comparative analysis within different pH ranges revealed that the sample with a pH of 7.5 exhibited a relatively low pH buffering capacity, a significant decrease in pH, a slight decrease in drug content, a significant increase in absorbance, and a high iodide level. Within the pH range of 5.0 to 7.0, the drug solution demonstrated a strong pH buffering capacity, relatively stable pH, minimal change in drug content, and a slight increase in absorbance, but this increase remained far below the standard limit (not exceeding 0.060). The iodine content of the solution was relatively low. The iodide level tends to decrease as the pH of the drug solution decreases, especially in the pH range of 5.0 to 6.5, where the iodide level is relatively low and far below the standard limit (not exceeding 40 μg / ml). Compared with the original formulation's pH range of 6.5 to 7.2 (ΔpH=0.7), this invention broadens the stable and adjustable pH range of the drug solution to 5.0 to 7.0 (ΔpH=2.0), making it easier to control during production, reducing the risk of batch scrap due to solution preparation failure, saving costs, and being more conducive to large-scale industrial production. Example

[0059] The injection solutions of Example 6 and Example 9 and the original formulation were heated to different temperatures, and their viscosity (viscosity unit mPa.s) was measured using a Brookfield DV3T rotational viscometer. The results are shown in Table 4.

[0060]

[0061] As can be seen from the rotational viscometer test results in Table 4, the viscosity of the buffer system of the present invention is lower than that of the original formulation, which can improve the compliance of clinical patients during use.

[0062] Comparative Example 1

[0063] Compared to Example 1, only the buffer solution and the acid used to adjust the pH are different; the rest of the steps are the same.

[0064] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of sodium acetate (the prescribed amount) and stir until completely dissolved, then add acetic acid to adjust the pH to 6.5; then add 81.65 g of iodine sorbitol in portions, stirring to dissolve, and keep warm for 10 min, then adjust the pH of the solution to 6.0 with acetic acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, and then filter through a 0.22 μm sterile filter cartridge before filling; finally, sterilize at 121°C for 15 min.

[0065] Compared to Example 1, only the buffer solution and the acid used to adjust the pH are different; the rest of the steps are the same.

[0066] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of potassium dihydrogen phosphate as prescribed and stir until completely dissolved, then add sodium hydroxide to adjust the pH to 6.5; then add 81.65 g of iodine methylphenidate in portions, stirring to dissolve, and keep warm for 10 min, then adjust the pH of the solution to 6.0 with sodium hydroxide, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill the container; finally, sterilize at 121°C for 15 min.

[0067] Compared to Example 1, only the buffer solution and the acid used to adjust the pH are different; the rest of the steps are the same.

[0068] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 200 mg of sodium tartrate (prescription amount) and stir until completely dissolved, then add tartaric acid to adjust the pH to 6.5; then add 81.65 g of iodine sorbitol in portions, stirring to dissolve, and keep warm for 10 min, then adjust the pH of the solution to 6.0 with tartaric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill the container; finally, sterilize at 121°C for 15 min.

[0069] Accelerated testing (40℃±2℃ / 75%RH±5%RH) was conducted on samples from Example 1 and Comparative Examples 1 to 3 for 6 months. The pH and iodide levels under initial and stability conditions were measured, and the data are shown in Table 5.

[0070]

[0071] The results in Table 5 show that, compared with Comparative Examples 1 to 3, the formulation of Example 1 of the present invention has a more stable pH value and a lower iodide level at 0 months, and its stability is even better after 6 months of accelerated processing.

[0072] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 100 mg of tromethorphan and stir until completely dissolved, then add hydrochloric acid to adjust the pH to 7.5–8.0; then add 81.65 g of iodine methylphenidate in portions, stirring to dissolve, and keep warm for 10 min, then adjust the pH of the solution to 6.5–7.2 with hydrochloric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill into the container; finally, sterilize.

[0073] Add 50%–90% of the total volume of water for injection to a plastic container, adjust the solution temperature to 60–90°C, add 100 mg of tromethorphan and stir until completely dissolved, then add hydrochloric acid to adjust the pH to 7.5–8.0; then add 81.65 g of iodine methylphenidate in portions, stirring to dissolve, and keep warm for 10 min, then adjust the pH of the solution to 6.5–7.2 with hydrochloric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, then filter through a 0.22 μm sterile filter cartridge, and fill the container; finally, sterilize.

[0074] Samples from Comparative Examples 4 and 5 were collected 0 days after sterilization and sent for testing of properties, absorbance, iodide, and other indicators. The test results are shown in Table 6.

[0075]

[0076] As shown in Table 6, according to the original formulation, compared to plastic containers, the solution prepared in stainless steel containers showed increased iodide levels and higher absorbance after sterilization for 0 days, indicating a deterioration in quality. The solution is more sensitive to metal ions.

[0077] Compared with Comparative Example 4, 60 ng / mL of copper sulfate aqueous solution was added, and the rest of the steps were the same.

[0078] Add 50%–90% of the total volume of water for injection to a stainless steel container, adjust the solution temperature to 60–90°C, add 100 mg of tromethorphan and stir until completely dissolved, then add hydrochloric acid to adjust the pH to 7.5–8.0; then add 81.65 g of iodine methylphenidate in portions, stirring to dissolve, and keep warm for 10 min; then add approximately 60 ng / ml of copper sulfate aqueous solution, and adjust the pH of the solution to 6.5–7.2 with hydrochloric acid, stir well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, and then filter through a 0.22 μm sterile filter cartridge before filling; finally, sterilize.

[0079] Compared with Comparative Example 4, 0.2 mg / mL of calcium sodium edetate and 60 ng / mL of copper sulfate aqueous solution containing divalent copper ions were added, and the remaining steps were the same.

[0080] Add 100 mL of water for injection to a stainless steel container, adjust the solution temperature to 60–90 °C, add 100 mg of tromethorphan and stir until completely dissolved, then add hydrochloric acid to adjust the pH to 7.5–8.0, add calcium sodium edetate and stir to dissolve; then add 81.65 g of iodine sorbitol in portions, stirring to dissolve, and keep warm for 10 min; then add approximately 60 ng / mL of copper sulfate aqueous solution, and adjust the pH of the solution to 6.5–7.2 with hydrochloric acid, stir to mix well, and bring the volume to 100 mL; filter the solution through a 0.45 μm filter cartridge, then ultrafilter, and then filter through a 0.22 μm sterile filter cartridge before filling; finally, sterilize.

[0081] Samples from Examples 2, 3, 6, and 7 were collected 0 days after sterilization, and samples were collected at 40℃ for 6 months. Their properties, absorbance, iodide content, and other indicators were tested. The results are shown in Table 7.

[0082]

[0083] In Examples 3, 6, and 7, a copper sulfate aqueous solution of 60 ng / mL was added. The copper sulfate aqueous solution was added because the product has a high concentration and osmotic pressure, and other non-ferrous ions, such as copper ions, may be introduced into the raw materials, packaging, and production equipment, affecting product quality. Adding the copper sulfate aqueous solution can simulate the copper ions introduced into the raw materials, packaging, and production equipment.

[0084] As shown in Table 7, compared to Comparative Examples 4 and 5 without the addition of a certain concentration of copper ions, Comparative Example 6, which used the original formulation with the addition of a certain concentration of copper ions, showed a significant increase in absorbance, an increase in iodide, and a decrease in content. This indicates that this product is sensitive to certain metal ions; copper, iron, and other metal ions can easily cause degradation, discoloration, and increased iodide levels in the solution. Therefore, appropriate metal ion chelating agents are needed to improve product stability.

[0085] Sodium edetate is a commonly used chelating agent in injections, but its clinical use carries risks. The use of sodium edetate in intravenous injections needs to be strictly controlled. Sodium edetate can bind with calcium ions to form soluble complexes, which can lead to a decrease in blood calcium levels. The potential clinical problems that may arise need to be fully considered.

[0086] The results of Comparative Example 7, Example 2, and Example 3 show that the combination of sodium citrate and citric acid used in this invention can maintain the long-term stability of the drug solution without using sodium edetate. After accelerated sample retention, the various detection indicators are significantly better than those of the original formulation.

[0087] Finally, it should be noted that the above descriptions are merely embodiments of this application, used only to illustrate the technical solutions of the present invention, and are not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principle of this application should be included within the scope of the claims of this application.

Claims

1. Iomethylperoxide injection, characterized in that, It consists of iodide, sodium citrate, citrate pH adjuster, and water for injection, with a pH of 5.0 to 7.

0.

2. The injectable solution according to claim 1, characterized in that, The mass ratio of iodomeprazole to sodium citrate is 60~90:0.1~3.

3. The injectable solution according to claim 2, characterized in that, The mass ratio of iodomeprazole to sodium citrate is 60~85:0.1~2.

0.

4. The injectable solution according to claim 1, wherein The volume of the water for injection is 40% to 95% of that of iodine-methyl injection.

5. The injection solution according to claim 4, characterized in that, The volume of the water for injection is 50% to 90% of that of iodine-methyl injection.

6. The injection solution according to claim 1, characterized in that, Each 100mL of injection solution contains: 81.65g iodine-methyl and 0.2g sodium citrate.

7. The injection solution according to claim 1, characterized in that, The viscosity of the injection solution is less than 28 mPa·s.

8. The method for preparing iodine-methyl injection according to any one of claims 1 to 7, characterized in that, Includes the following steps: (1) Dissolve sodium citrate and adjust the pH with citric acid to 7.0-8.5; (2) Add iodine methylphenidate, stir to dissolve, and adjust the pH to 5.0~7.0; (3) Filtration and filling; (4) Sterilization and packaging.

9. The preparation method according to claim 8, characterized in that, In step 1, adjust the pH to 7.5~8.

0.

10. The preparation method according to any one of claims 8 to 9, characterized in that, The temperature in step (1) is 50~100℃.

11. The preparation method according to claim 10, characterized in that, The temperature is 60~90℃.

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