Cilnidipine injection and preparation method thereof

Abstract

The invention discloses a cilnidipine injection and a preparation method thereof, and belongs to the technical field of medicines. The cilnidipine injection mainly comprises cilnidipine, a cosolvent, a solubilizer, a stabilizer, an osmotic pressure regulator and water for injection, wherein the cosolvent comprises one or more of polyethylene glycol 400, propylene glycol and ethanol; the solubilizer comprises Tween 80 and SDS (sodium dodecyl sulfate); the stabilizer comprises sodium pyrosulfite and sodium hydrogen sulfite. The cilnidipine injection prepared by the invention not only has the characteristics of high in-vivo bioavailability, good stability, small use amount of solubilizer, medication safety and the like, but also is simple in preparation process, convenient to operate, low in production cost and suitable for industrial large-scale production.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medicine, in particular to a cilnidipine injection and a preparation method thereof. BACKGROUND

[0002] Cilnidipine is a new dihydropyridine derivative, which was developed by Fuji Corporation of Japan and first marketed in Japan in 1995. It is the third generation of lipophilic dihydropyridine calcium antagonists, which can bind to the dihydropyridine site of L-type calcium channel on the membrane of vascular smooth muscle cells, inhibit the transmembrane influx of Ca 2+ through L-type calcium channels, thereby relaxing and dilating vascular smooth muscle, and playing a role in lowering blood pressure. It can also inhibit the release of norepinephrine and sympathetic nerve activity by inhibiting the transmembrane influx of Ca 2+ through N-type calcium channels on the membrane of sympathetic nerve cells, and has a high comprehensive therapeutic effect on lowering blood pressure and anti-atherosclerosis, and can also be used for preventing high-risk heart attack induced by sympathetic nerve activity.

[0003] Hypertension is a phenomenon in which the pressure value caused by blood flowing in blood vessels against the blood vessel wall is continuously higher than normal. Hypertension is often referred to as the "silent killer", and the main complications include coronary heart disease, myocardial infarction, stroke, etc. Severe hypertension can cause hypertensive crisis, and even endanger life. Hypertension has become one of the most common cardiovascular diseases and major fatal diseases worldwide. Therefore, how to effectively control hypertension is a major public health problem we are facing.

[0004] As a poorly soluble drug, cilnidipine is insoluble in water, which greatly restricts its clinical application. At present, only two dosage forms of tablets and capsules have been marketed, the in vivo bioavailability is relatively low, and the absorption difference between individuals is large, which also significantly affects the clinical therapeutic effect of cilnidipine. In addition, in order to improve the solubility and dissolution of poorly soluble drugs and thus improve the bioavailability, the commonly used and effective way is to prepare solid dispersions, which has a relatively complex production process and high production cost, and also requires a large amount of organic solvents in the preparation process, increasing the environmental pressure.

[0005] Injection is a sterile preparation directly injected into human tissues, which has the characteristics of fast onset and high bioavailability, is suitable for patients who cannot take oral drugs or cannot take oral drugs, has precise dosage and avoids first-pass effect. At present, there is no related report on cilnidipine injection.

[0006] Therefore, it is necessary to develop a blood pressure lowering injection which can improve the in vivo bioavailability, has stable quality, has a simple preparation process and low production cost, and is safe and has few side effects. SUMMARY

[0007] The purpose of this invention is to provide a cilnidipine injection solution to improve the bioavailability and speed of drug action of cilnidipine and avoid the first-pass effect.

[0008] The present invention also aims to provide a method for preparing cilnidipine injection, which can be used to prepare cilnidipine injection with high bioavailability, stable quality, low production cost and few side effects.

[0009] In a first aspect, the present invention provides a cilnidipine injection solution, which is composed of cilnidipine, a solubilizer, a solvent, a stabilizer, an osmotic pressure regulator and water for injection.

[0010] By employing the above technical solutions, poorly soluble cilnidipine can be prepared into an injectable form, directly avoiding the first-pass effect of oral administration. The drug can directly enter the bloodstream through injection, improving bioavailability. This solution utilizes the synergistic effect of solubilizers and cosolvents to improve the solubility of cilnidipine in water; stabilizers are used to inhibit possible oxidative degradation of cilnidipine injection during storage or use, ensuring the stability of the injection solution; and osmotic pressure regulators are used to adjust the osmotic pressure of cilnidipine injection to match that of human body fluids, avoiding vascular irritation caused by osmotic pressure imbalance.

[0011] Preferably, the co-solvent includes one or more of polyethylene glycol 400, propylene glycol and ethanol.

[0012] Preferably, the mass ratio of the cosolvent to cinidipine is (80-200):1.

[0013] More preferably, the mass ratio of the cosolvent to cinidipine is (80-150):1.

[0014] Preferably, the solubilizer includes Tween 80 and SDS.

[0015] Preferably, the mass ratio of solubilizer to cinidipine is (8-20):1.

[0016] More preferably, the mass ratio of the solubilizer to cinidipine is (8-15):1.

[0017] Preferably, the stabilizer includes sodium metabisulfite and sodium bisulfite.

[0018] Preferably, the mass ratio of stabilizer to cinidipine is (5-20):1.

[0019] More preferably, the mass ratio of stabilizer to cinidipine is (5-15):1.

[0020] Preferably, the osmotic pressure regulator includes sodium chloride and glucose.

[0021] Preferably, the mass ratio of the osmotic pressure regulator to silnidipine is (50-600):1.

[0022] On the other hand, the present invention also provides a method for preparing cinidipine injection, comprising the following steps: S1. Dissolve cinidipine in a co-solvent to obtain the first solution; S2. Dissolve the solubilizer in water for injection, slowly add the first solution, then add the stabilizer and osmotic pressure regulator, then adjust the pH value to 4.5-6.0 with the pH regulator, stir and add water for injection to obtain the second solution; S3. Filter, fill and sterilize the second liquid to obtain cinidipine injection.

[0023] Preferably, the mass ratio of cinidipine to water for injection is 1:(9300-9900).

[0024] Preferably, in step S2, the pH adjuster includes one or a combination of several of hydrochloric acid, phosphoric acid, acetic acid, methanesulfonic acid, sodium hydroxide, and sodium carbonate.

[0025] Preferably, in step S3, the filling is done in brown vials filled with protective gas; the concentration of the cinidipine injection after filling is 0.1 mg / mL.

[0026] More preferably, the protective gas includes nitrogen, argon, and helium.

[0027] Preferably, in step S3, the sterilization conditions are moist heat sterilization at 121°C for 15 minutes.

[0028] The beneficial effects of this invention are: 1. This invention solves the problem of cilnidipine's poor water solubility by adding small amounts of solubilizers and co-solvents, and ensures the stable function of the active ingredient in cilnidipine injection by adding stabilizers and osmotic pressure regulators. Using the cilnidipine injection of this invention not only improves the bioavailability of cilnidipine in vivo, but also ensures stable quality and good safety.

[0029] 2. The cinidipine injection obtained using the preparation method of the present invention has a simple preparation process, is easy to operate, does not require complex equipment, has low production cost, and is suitable for large-scale industrial production. Detailed Implementation

[0030] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below.

[0031] A cilnidipine injection solution is composed of cilnidipine, solubilizer, solvent, stabilizer, osmotic pressure regulator and water for injection.

[0032] The poor water solubility of cilnidipine greatly limits its clinical application. This solution utilizes the synergistic effect of solubilizers and co-solvents to improve the solubility of cilnidipine in water; stabilizers are used to inhibit the oxidative degradation that may occur during the storage or use of cilnidipine injection, ensuring the stability of the injection quality; and osmotic pressure is adjusted by osmotic pressure regulators to keep it consistent with human body fluids, avoiding vascular irritation caused by osmotic pressure imbalance.

[0033] In some embodiments, the co-solvent is one of polyethylene glycol 400, propylene glycol, and ethanol. Using the co-solvent can effectively disrupt the crystal structure of cilnidipine molecules, initially improving its dispersibility in different environments and laying the foundation for solubilization in aqueous solutions. The mass ratio of cilnidipine to co-solvent is 1:(80–200), more preferably 1:(80–150). Using this range of mass ratios ensures that cilnidipine is fully dissolved while avoiding potential safety risks associated with excessive co-solvent usage.

[0034] In some embodiments, the solubilizer is Tween 80 or SDS. By using the solubilizer, it can work synergistically with the cosolvent to encapsulate the cilnidipine molecules dispersed by the cosolvent through mechanisms such as micelle formation, thereby stably solubilizing them in the aqueous phase. The mass ratio of cilnidipine to solubilizer is 1:(8-20), and a more preferred mass ratio is 1:(8-15). Using a mass ratio within this range allows for control of the amount of solubilizer used while ensuring the formation of a sufficient number of micelles to completely solubilize the drug, thus ensuring the biocompatibility and safety of the formulation.

[0035] In some embodiments, the stabilizer is sodium metabisulfite or sodium bisulfite. Using the stabilizer further inhibits the oxidation of active groups such as the dihydropyridine structure in the cilnidipine molecule by oxygen during production and storage, preventing drug degradation and reduced efficacy. The mass ratio of cilnidipine to stabilizer is 1:(5-20), more preferably 1:(5-15). This range of mass ratios provides a sufficient reducing environment for effective oxidation resistance while avoiding the introduction of unnecessary impurities from excessive stabilizer.

[0036] In some embodiments, the osmotic pressure regulator is sodium chloride or glucose. By adding the osmotic pressure regulator, the osmotic pressure of the injection solution can be made similar to that of human plasma, thus becoming an isotonic solution and improving the safety of the injection. The mass ratio of cinidipine to the osmotic pressure regulator is 1:(50-600). Using this range of mass ratios can adjust the osmotic pressure of the injection solution to the physiological isotonic range.

[0037] In some embodiments, the water for injection is sterile, pyrogen-free purified water, which serves as the base solvent for the injection solution.

[0038] A method for preparing cinidipine injection includes the following steps: S1. Dissolve cinidipine in a co-solvent to obtain the first solution; Dissolving cilnidipine in a solubilizer and completely dissolving it in a non-aqueous environment to form a homogeneous solution is a key initial step in overcoming its poor water solubility.

[0039] S2. Dissolve the solubilizer in water for injection, slowly add the first solution, then add the stabilizer and osmotic pressure regulator, then adjust the pH value to 4.5-6.0 with the pH regulator, stir and add water for injection to obtain the second solution; By adding solubilizers, stabilizers, and osmotic pressure regulators and distributing them, a stable, isotonic aqueous medium system capable of accommodating cilnidipine molecules can be constructed. The pH is then adjusted to 4.5–6.0 using a pH adjuster; this pH range helps maintain the chemical stability of cilnidipine.

[0040] S3. Filter, fill and sterilize the second liquid to obtain cinidipine injection.

[0041] Filtering, filling, and sterilizing the second solution can remove any small particulate impurities and microorganisms that may be present in cilnidipine injection, ensuring the sterility, pyrogen-free nature, and clarity requirements of the injection, ultimately yielding a finished product that meets the quality standards for injectables.

[0042] In some embodiments, the mass ratio of cinidipine to water for injection is 1:(9300-9900), which ensures that the final injection solution has an appropriate volume and drug concentration.

[0043] In some embodiments, the pH adjuster includes one or more of hydrochloric acid, phosphoric acid, acetic acid, methanesulfonic acid, sodium hydroxide, and sodium carbonate, and the pH value is adjusted to 4.5 to 6.0 by the pH adjuster to optimize the stability of the drug and the compatibility of the solution.

[0044] In some embodiments, the filling is performed in brown vials filled with a protective gas to isolate light and oxygen; the concentration of the cilnidipine injection after filling is 0.1 mg / mL.

[0045] In some embodiments, the protective gas includes nitrogen, argon, and helium. By filling the vial with a protective gas, the air, especially oxygen, in the top space of the vial can be replaced, thereby maximizing the prevention of oxidation of the active pharmaceutical ingredient during the shelf life of the drug and further improving the long-term stability of the product.

[0046] In some embodiments, the sterilization conditions are moist heat sterilization at 121°C for 15 minutes, which can ensure the sterility level of the cilnidipine injection product and meet the pharmacopoeia requirements for sterilization of injections.

[0047] The specific embodiments of the present invention will be described in detail below, but it should be understood that the scope of protection of the present invention is not limited to the specific embodiments.

[0048] Example

[0049] Example 1: A cinidipine injection solution was prepared by the following method: S1. Dissolve 1g of cinidipine in 100g of polyethylene glycol 400 solvent to obtain the first solution; S2. Dissolve 8g of Tween 80 in 9500g of water for injection. Slowly add the first solution to the solution, then add 10g of sodium metabisulfite and 90g of sodium chloride. Adjust the pH to 5.5 using 1mol / L hydrochloric acid and 5% sodium hydroxide solution. Stir and add water for injection to 10000g to obtain the second solution. S3. Filter the second liquid, fill it with nitrogen gas, and sterilize it at 121°C for 15 minutes to obtain cinidipine injection.

[0050] Example 2, a cinidipine injection solution, obtained by the following preparation method: S1. Dissolve 1g of cinidipine in 80g of polyethylene glycol 400 solvent to obtain the first solution; S2. Dissolve 8g of Tween 80 in 9500g of water for injection. Slowly add the first solution to the solution, then add 10g of sodium metabisulfite and 90g of sodium chloride. Adjust the pH to 5.5 using 1mol / L hydrochloric acid and 5% sodium hydroxide solution. Stir and add water for injection to 10000g to obtain the second solution. S3. Filter the second liquid, fill it with nitrogen gas, and sterilize it at 121°C for 15 minutes to obtain cinidipine injection.

[0051] Example 3, a cinidipine injection solution, obtained by the following preparation method: S1. Dissolve 1g of cinidipine in 200g of polyethylene glycol 400 solvent to obtain the first solution; S2. Dissolve 8g of Tween 80 in 9500g of water for injection. Slowly add the first solution to the solution, then add 10g of sodium metabisulfite and 90g of sodium chloride. Adjust the pH to 5.5 using 1mol / L hydrochloric acid and 5% sodium hydroxide solution. Stir and add water for injection to 10000g to obtain the second solution. S3. Filter the second liquid, fill it with nitrogen gas, and sterilize it at 121°C for 15 minutes to obtain cinidipine injection.

[0052] Example 4: A cinidipine injection solution, prepared by the following method: S1. Dissolve 1g of cinidipine in 100g of propylene glycol solvent to obtain the first solution; S2. Dissolve 8g of Tween 80 in 9500g of water for injection. Slowly add the first solution to the solution, then add 10g of sodium metabisulfite and 90g of sodium chloride. Adjust the pH to 5.5 using 1mol / L hydrochloric acid and 5% sodium hydroxide solution. Stir and add water for injection to 10000g to obtain the second solution. S3. Filter the second liquid, fill it with nitrogen gas, and sterilize it at 121°C for 15 minutes to obtain cinidipine injection.

[0053] Example 5, a cinidipine injection solution, prepared by the following method: S1. Dissolve 1g of cinidipine in 100g of polyethylene glycol 400 solvent to obtain the first solution; S2. Dissolve 20g of Tween 80 in 9500g of water for injection. Slowly add the first solution to the solution, then add 10g of sodium metabisulfite and 90g of sodium chloride. Adjust the pH to 5.5 using 1mol / L hydrochloric acid and 5% sodium hydroxide solution. Stir and add water for injection to 10000g to obtain the second solution. S3. Filter the second liquid, fill it with nitrogen gas, and sterilize it at 121°C for 15 minutes to obtain cinidipine injection.

[0054] Example 6: A cinidipine injection solution was prepared by the following method: S1. Dissolve 1g of cinidipine in 100g of polyethylene glycol 400 solvent to obtain the first solution; S2. Dissolve 8g SDS in 9500g water for injection. Slowly add the first solution to the solution, then add 10g sodium metabisulfite and 90g sodium chloride. Adjust the pH to 5.5 using 1mol / L hydrochloric acid and 5% sodium hydroxide solution. Stir and add water for injection to 10000g to obtain the second solution. S3. Filter the second liquid, fill it with nitrogen gas, and sterilize it at 121°C for 15 minutes to obtain cinidipine injection.

[0055] Example 7, a cinidipine injection solution, prepared by the following method: S1. Dissolve 1g of cinidipine in 100g of polyethylene glycol 400 solvent to obtain the first solution; S2. Dissolve 8g of Tween 80 in 9500g of water for injection. Slowly add the first solution to the solution, then add 5g of sodium metabisulfite and 90g of sodium chloride. Adjust the pH to 5.5 using 1mol / L hydrochloric acid and 5% sodium hydroxide solution. Stir and add water for injection to 10000g to obtain the second solution. S3. Filter the second liquid, fill it with nitrogen gas, and sterilize it at 121°C for 15 minutes to obtain cinidipine injection.

[0056] Example 8, a cinidipine injection solution, obtained by the following preparation method: S1. Dissolve 1g of cinidipine in 100g of polyethylene glycol 400 solvent to obtain the first solution; S2. Dissolve 8g of Tween 80 in 9500g of water for injection. Slowly add the first solution to the solution, then add 20g of sodium metabisulfite and 90g of sodium chloride. Adjust the pH to 5.5 using 1mol / L hydrochloric acid and 5% sodium hydroxide solution. Stir and add water for injection to 10000g to obtain the second solution. S3. Filter the second liquid, fill it with nitrogen gas, and sterilize it at 121°C for 15 minutes to obtain cinidipine injection.

[0057] Example 9, a cinidipine injection solution, obtained by the following preparation method: S1. Dissolve 1g of cinidipine in 100g of polyethylene glycol 400 solvent to obtain the first solution; S2. Dissolve 8g of Tween 80 in 9500g of water for injection. Slowly add the first solution to the solution, then add 10g of sodium bisulfite and 90g of sodium chloride solution. Adjust the pH to 5.5 with 1mol / L hydrochloric acid and 5% sodium hydroxide solution. Stir and add water for injection to 10000g to obtain the second solution. S3. Filter the second liquid, fill it with nitrogen gas, and sterilize it at 121°C for 15 minutes to obtain cinidipine injection.

[0058] Example 10, a cinidipine injection solution, obtained by the following preparation method: S1. Dissolve 1g of cinidipine in 100g of polyethylene glycol 400 solvent to obtain the first solution; S2. Dissolve 8g of Tween 80 in 9000g of water for injection. Slowly add the first solution to the solution, then add 10g of sodium metabisulfite and 500g of glucose. Adjust the pH to 5.5 with 1mol / L hydrochloric acid and 5% sodium hydroxide solution. Stir and add water for injection to 10000g to obtain the second solution. S3. Filter the second liquid, fill it with nitrogen gas, and sterilize it at 121°C for 15 minutes to obtain cinidipine injection.

[0059] Example 11, a cinidipine injection, differs from Example 1 only in that nitrogen is not used for filling in step S3.

[0060] Comparative Example

[0061] Comparative Example 1, a cinidipine injection, differs from Example 1 only in that no solubilizer is added.

[0062] Comparative Example 2, a cinidipine injection, differs from Example 3 only in that no solubilizer is added.

[0063] Comparative Example 3, a cinidipine injection, differs from Example 3 only in that the amount of solubilizer added is 5g.

[0064] Comparative Example 4, a cinidipine injection, differs from Example 1 only in that no solubilizer is added.

[0065] Comparative Example 5, a cinidipine injection, differs from Example 5 only in that no cosolvent is added.

[0066] Comparative Example 6, a cinidipine injection, differs from Example 1 only in that it does not contain a stabilizer.

[0067] Comparative Example 7, a cinidipine injection, differs from Example 11 only in that it does not contain a stabilizer.

[0068] Performance testing: 1. Sample properties and dissolution test: Observe the properties of the cinidipine injection prepared in Examples 1 to 11 and Comparative Examples 1 to 6, whether cinidipine precipitates, and whether the solution is colorless and clear; observe the dissolution time, which is the time when all the cinidipine raw material is completely dissolved. The results are shown in Table 1. 2. Stability Testing: The cinidipine injection solutions prepared in Examples 1-11 and Comparative Examples 6-7 were placed in a stability test chamber for accelerated and long-term tests. The accelerated testing conditions were 40℃±2℃ and 75%RH±5%RH; the long-term testing conditions were 25℃±2℃ and 60%RH±10%RH. Samples were taken at 0, 1, 3, and 6 months for the accelerated testing, and at 0, 3, 6, and 12 months for the long-term testing to examine changes in properties, pH value, related substances, and content.

[0069] 2.1 Detection of related substances

[0070] The determination was performed according to the high-performance liquid chromatography (HPLC) method (Chinese Pharmacopoeia 2020 Edition, Part IV, General Chapter 0512). The procedure was carried out in the dark. Test solution: Take the sample directly. Reference solution: Accurately measure 3 mL of the test solution and place it in a 200 mL volumetric flask. Dilute to the mark with the mobile phase and mix well. Chromatographic conditions: Use perfluorohexylpropylsilanized silica gel (4.6 mm × 250 mm, 5 μm) as the stationary phase; use 0.01 mol / L sodium acetate trihydrate solution-methanol (v / v, pH 5.5, 40:60); detection wavelength: 240 nm; column temperature: 25℃; injection volume: 10 μL; adjust the flow rate to ensure the retention time of the cinidadipine peak is approximately 20 minutes. Accurately measure the test solution and reference solution and inject them separately into the HPLC system.

[0071] The known impurities and other unknown impurities in the test solution are calculated using the principal component self-comparison method. Known impurity A shall not exceed 0.5%, and known impurities B, C, D, E, and other unknown impurities shall not exceed 0.2%. Total impurities shall not exceed 1.5%. Impurity B is an oxidizing impurity.

[0072] 2.2 Determination of Cialis Content

[0073] Determine the cinidipine solution according to the high-performance liquid chromatography (HPLC) method (Chinese Pharmacopoeia 2020 Edition, Part IV, General Chapter 0512). Operate in the dark. Test solution: Accurately pipette 5 mL of this product into a 25 mL volumetric flask, add mobile phase to dilute to the mark, and mix well. Reference solution: Accurately weigh 10 mg of cinidipine standard, place it in a 20 mL volumetric flask, add mobile phase to dissolve and dilute to the mark; accurately pipette 5 mL of this solution into a 25 mL volumetric flask, add mobile phase to dissolve and dilute to the mark, and mix well. Chromatographic conditions: Use octadecyl bonded silica gel as the column packing material (6 mm × 300 mm, 5 μm); use 0.01 mol / L disodium hydrogen phosphate dodecahydrate solution-acetonitrile (v / v, pH 6.0, 40:60); adjust the flow rate to achieve a retention time of approximately 23 min for cinidipine; use a detection wavelength of 240 nm; maintain a column temperature of 40 °C; and inject a volume of 10 μL. Accurately measure the test solution and reference solution, and inject them separately into the liquid chromatograph. Calculate the content based on peak area using the external standard method. The content of cinidipine is between 95% and 105%.

[0074] The properties, pH values, related substances, and content determination results of Examples 1 to 9 and Comparative Examples 6 to 7 in accelerated and long-term stability tests are shown in Tables 2 and 3: Table 1: Results of Properties and Dissolution Time of Each Test Sample

[0075] Table 2: Results of accelerated testing at 40℃

[0076] Table 3: Long-term test results at 25℃

[0077] The above results indicate that, compared with the comparative example, the cilnidipine injection provided by this invention exhibits significantly improved cilnidipine solubility, and the solution is a colorless and clear liquid. After accelerated and long-term experiments, the quality indicators of the examples showed no significant changes, while the quality indicators of the comparative example showed significant changes, especially a substantial increase in oxidized impurity B and a decrease in cilnidipine content, exceeding the limit values.

[0078] In summary, the cilnidipine injection provided by this invention exhibits good quality stability, high bioavailability in vivo, and meets the quality requirements for long-term storage. Simultaneously, the amounts of solubilizer and co-solvent used are both low, ensuring good solubility of cilnidipine while reducing the risk of irritation and hemolysis during intravenous injection, thus improving medication safety. The production process is simple, low-cost, safe, and environmentally friendly.

[0079] The above-disclosed embodiments are merely a few specific examples of the present invention. However, the embodiments of the present invention are not limited thereto, and any variations that can be conceived by those skilled in the art should fall within the protection scope of the present invention.

Claims

1. A cinidipine injection solution, characterized in that, It consists of cinidipine, solubilizer, solvent, stabilizer, osmotic pressure regulator and water for injection.

2. The cinidipine injection solution according to claim 1, characterized in that, The co-solvent comprises one or more of polyethylene glycol 400, propylene glycol and ethanol; the mass ratio of the co-solvent to cinidipine is (80-200):

1.

3. The cinidipine injection solution according to claim 1, characterized in that, The solubilizer includes Tween 80 and SDS; the mass ratio of the solubilizer to sildenafil is (8-20):

1.

4. A cinidipine injection solution according to claim 1, characterized in that, The stabilizer includes sodium metabisulfite and sodium bisulfite; the mass ratio of the stabilizer to cinidipine is (5-20):

1.

5. A cinidipine injection solution according to claim 1, characterized in that, The osmotic pressure regulator includes sodium chloride and glucose; the mass ratio of the osmotic pressure regulator to silnidipine is (50-600):

1.

6. A method for preparing cilnidipine injection, used to prepare the cilnidipine according to any one of claims 1-5, characterized in that, Includes the following steps: S1. Dissolve cinidipine in a co-solvent to obtain the first solution; S2. Dissolve the solubilizer in water for injection, slowly add the first solution, then add the stabilizer and osmotic pressure regulator, then adjust the pH value to 4.5-6.0 with the pH regulator, stir and add water for injection to obtain the second solution; S3. Filter, fill and sterilize the second liquid to obtain cinidipine injection.

7. The method for preparing cinidipine injection according to claim 6, characterized in that, The mass ratio of cinidipine to water for injection is 1:(9300-9900).

8. The method for preparing cinidipine injection according to claim 6, characterized in that, In step S2, the pH adjuster includes one or a combination of several of hydrochloric acid, phosphoric acid, acetic acid, methanesulfonic acid, sodium hydroxide, and sodium carbonate.

9. The method for preparing cinidipine injection according to claim 6, characterized in that, In step S3, the filling is carried out in brown vials filled with protective gas; the concentration of the cilnidipine injection after filling is 0.1 mg / mL.

10. The method for preparing cinidipine injection according to claim 6, characterized in that, In step S3, the sterilization conditions are 121°C moist heat sterilization for 15 minutes.

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