Nimodipine injection and preparation method thereof

Abstract

The invention discloses nimodipine injection and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The nimodipine injection comprises nimodipine, sucrose stearate, propylene glycol, vitamin E TPGS, a histidine buffer solution, mannitol and water for injection. Stable micelles are formed by sucrose stearate and vitamin E TPGS, the histidine buffer solution inhibits oxidative degradation, and the mannitol regulates osmotic pressure, so that the solubility and stability of the medicine are synergistically improved. The preparation method comprises the steps of buffer solution preparation, main medicine solution mixing, filtering and sterilization and the like. The injection provided by the invention is clear and transparent in accelerated test and long-term storage, the total impurity content is less than or equal to 0.28%, and no crystal is separated out; safety tests show that hemolysis and anaphylaxis are avoided, and irritation to blood vessels and muscles is low.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to a nimodipine injection and a preparation method thereof. Background Art

[0002] Nimodipine is a dihydropyridine calcium channel blocker with the chemical name 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate. Its structural formula is as follows:

[0003]

[0004] Nimodipine improves ischemic nerve damage caused by cerebral vasospasm after subarachnoid hemorrhage (SAH) by selectively dilating cerebral blood vessels. It is widely used clinically to prevent and treat cerebrovascular diseases such as migraine, sudden deafness, and Alzheimer's disease.

[0005] However, nimodipine has extremely low water solubility, is practically insoluble in water, and exhibits significant propensity for photodegradation and oxidative degradation, making its formulation development a significant challenge. Currently available formulations include oral capsules and injections, but both have significant drawbacks and are in urgent need of improvement.

[0006] Oral nimodipine, such as Due to the severe first-pass effect in the liver, the bioavailability of the capsule is only 5%-15%. Frequent dosing is required to maintain effective blood concentrations, which can easily lead to peaks and valleys and toxic side effects. For patients who are unable to swallow, such as those in a coma after surgery, the capsule contents must be withdrawn via needle and administered through the nasogastric tube. This procedure is cumbersome and makes it difficult to ensure accurate dosing.

[0007] There are currently commercially available nimodipine injections, such as 23.7% (v / v) ethanol and 17% (v / v) polyethylene glycol 400 (PEG400) are used as solubilizers. Although ethanol and PEG400 can increase the solubility of nimodipine, their combined proportion is as high as 40.7%, leading to vascular irritation problems. High concentrations of ethanol cause pain at the injection site, phlebitis, and poor patient compliance. Clinical use is limited because it needs to be diluted and infused in a 1:4 ratio with 5% glucose or normal saline through a three-way valve. The operation is complicated and there is a risk of uncontrolled mixing ratios, which can easily lead to drug crystallization. In addition, the solvent ethanol in the injection is potentially harmful to patients with impaired alcohol metabolism, pregnant women, and lactating women.

[0008] While existing technologies have addressed issues with original injection solutions, the use of various surfactants and excipients presents significant drawbacks. For example, CN1183908C uses Tween 80 for solubilization, but this carries a high risk of hemolysis and can trigger allergic reactions. Patents such as CN115990262A use propylene glycol as a cosolvent, but clinical reports indicate it can easily cause metabolic acidosis and central nervous system depression. CN100386078C adds benzyl alcohol to its emulsion to improve solubility, but this ingredient is neurotoxic and has been restricted in several pharmacopoeias.

[0009] Cyclodextrin and its derivatives (such as hydroxypropyl-β-cyclodextrin and sulfobutyl ether-β-cyclodextrin) are widely used to solubilize nimodipine, but there are problems such as large amount of excipients, low inclusion efficiency, and safety disputes. For example, CN116889552A requires the mass ratio of sulfobutyl ether-β-cyclodextrin to nimodipine to be ≥500:1, resulting in an excessive proportion of excipients and high production costs. The side chain of the nimodipine molecule has large steric hindrance and is difficult to combine with β-cyclodextrin. It needs to rely on a high proportion of cyclodextrin or composite excipients, such as polyethylene glycol 400, which further increases the complexity of the process. Hydroxypropyl-β-cyclodextrin has the risk of nephrotoxicity and is prone to cause the appearance of the preparation to collapse during the freeze-drying process, such as the technical solution disclosed in CN1634050A.

[0010] While nanoformulation technologies such as fat emulsions, liposomes, and micelles can improve nimodipine solubility, they face technical bottlenecks such as complex processes, poor stability, and in vivo risks. For example, the lipid microspheres disclosed in CN101485632B require multiple steps, including homogenization and sonication, making scale-up difficult. The nanoparticles disclosed in CN107019682A are prone to aggregation, while the lipid nanoparticles disclosed in CN102552156B have a low drug loading of only 0.2 mg / mL and are prone to drug leakage during long-term storage.

[0011] The liposomes disclosed in CN105434355B are easily captured by the hepatosplenic reticuloendothelial system, which affects the efficacy and increases toxicity.

[0012] Based on existing patents and literature, the technical bottlenecks of nimodipine injection can be summarized as follows: strong dependence on organic solvents such as high-concentration ethanol or PEG400, which leads to safety issues; toxic surfactant excipients such as Tween 80 and propylene glycol, which can cause hemolysis, allergies, and metabolic risks. Processes such as cyclodextrin inclusion and nanoformulation are costly and prone to crystallization upon dilution. Existing solutions require excessive amounts of excipients to maintain solubility, resulting in bulky formulations and inconvenience in clinical use.

[0013] Based on this, the development of nimodipine injection, which achieves efficient solubilization, long-term stability and improved clinical safety of nimodipine through the synergistic effect of multiple components while avoiding traditional toxic excipients, has important clinical application value. Summary of the Invention

[0014] In order to solve the problems of nimodipine injection in the prior art caused by reliance on high-concentration organic solvents, toxic surfactants and complex preparation processes, such as vascular irritation, hemolysis risk, dilution crystallization and inconvenience in clinical use, the present invention provides an innovative formula and preparation method. The nimodipine injection comprises the following components (w / v):

[0015] Nimodipine: 0.02%

[0016] Sucrose stearate: 0.3-1.0%

[0017] Propylene glycol: 0.3-1.0%

[0018] Vitamin E TPGS: 0.05-0.2%

[0019] Histidine buffer: 0.1M (pH 6.5±0.1, adjusted with hydrochloric acid)

[0020] Mannitol: 3.0-5.0%

[0021] Water for injection: add to 100%

[0022] Preferably, the vitamin E TPGS is 0.1-0.2%

[0023] Using the technical solution of the present invention, the sucrose stearate hydrophobic chain (stearic acid) encapsulates the nimodipine molecule, and the hydrophilic chain (sucrose) combines with water to form micelle solubilization, with a critical micelle concentration as low as 0.1%, achieving efficient solubilization. The imidazole group of histidine has the strongest buffering capacity near pH 6.5, inhibiting the oxidation of nimodipine nitrophenyl. Compared with citrate, histidine reduces the risk of metal ion catalytic degradation. Mannitol provides an osmotic pressure that matches the physiological environment, reducing injection pain. The technical solution of the present invention can inhibit the aggregation of nimodipine molecules, and no crystallization is precipitated during long-term storage. The generation of oxidative dehydrogenation product impurity I can be avoided.

[0024]

[0025] The histidine buffer is composed of the following components in terms of volume percentage of the total weight of the final product:

[0026] L-histidine: 0.25% (w / v)

[0027] Hydrochloric acid (HCl, for adjusting pH): appropriate amount (pH 6.5±0.1)

[0028] Water for injection: as solvent.

[0029] The advantage of using histidine buffer is that the weakly acidic environment in the pH range of 6.5±0.1 can inhibit the oxidative degradation of nimodipine to the greatest extent, while avoiding excessive acidity that causes hydrolysis of excipients. Histidine has a pKa value of 6.0 and has optimal buffering capacity around pH 6.5, which can effectively offset the acidic byproducts produced by the degradation of nimodipine and reduce the production of related substances. Compared with citric acid or EDTA buffers, histidine has a lower chelating ability for metal ions, avoiding catalysis of nimodipine oxidation reactions. Histidine is a natural amino acid in the human body and has no risk of hemolysis or vascular irritation. It has good compatibility with sucrose stearate and vitamin E TPGS, and there is no risk of phase separation or precipitation. Histidine does not decompose under high-temperature sterilization conditions (121°C, 15 minutes), avoiding the formation of impurities.

[0030] Preferably, the nimodipine injection comprises the following components (w / v):

[0031] Nimodipine: 0.02%

[0032] Sucrose stearate: 0.5%

[0033] Propylene glycol: 0.5%

[0034] Vitamin E TPGS: 0.1%

[0035] Histidine buffer: 0.1M (pH 6.5±0.1, adjusted with hydrochloric acid)

[0036] Mannitol: 4.0%

[0037] Water for injection: add to 100%

[0038] On the other hand, the present invention provides a method for preparing the nimodipine injection, comprising the steps of:

[0039] (1) Preparation of histidine buffer: Weigh the prescribed amount of histidine and dissolve it in water for injection. Heat and stir until completely dissolved. Adjust the pH to 6.5 ± 0.1 with hydrochloric acid and cool to room temperature.

[0040] (2) Preparation of nimodipine injection: sucrose stearate was slowly added to propylene glycol while stirring, and the mixture was heated until completely dissolved. Nimodipine was added and stirred continuously until a homogeneous transparent solution was formed. Vitamin E-TPGS was added to prepare a main drug solution, which was then slowly added to the histidine buffer prepared in step (1). Mannitol was added to prepare a nimodipine solution with a pH of 6.5±0.1.

[0041] (3) Filtration and sterilization: The nimodipine liquid is sterilized and filtered, filled, sealed, and sterilized by moist heat to prepare the nimodipine injection.

[0042] The nimodipine injection provided by the present invention has significant advantages in terms of stability and safety. The accelerated stability test of Example 3 verified that the preferred formula of the present invention remained clear and transparent within 6 months, the pH value was stable in the range of 6.3-6.5, the oxidative degradation product impurity I was not detected, the total impurity content only increased from the initial 0.06% to 0.18%, and the drug content was always maintained at 99.7%-100.9%, meeting the stability requirements specified in the pharmacopoeia. Preferably, the long-term stability test of Example 4 further demonstrated that the injection remained clear and transparent within 24 months, no crystallization was precipitated, the total impurities slowly accumulated to 0.28%, and the content retention rate was ≥99.1%, indicating that it can be stably stored for at least 24 months, and the clinical use period is significantly better than that of existing commercially available products.

[0043] In terms of safety, as shown in Example 5, the nimodipine injection of the present invention did not induce allergic reactions in passive skin allergy tests and active systemic allergy tests, and there was no hemolysis or agglutination in the hemolysis test. The vascular irritation score of 0.2±0.1 and the muscle irritation score of 0.3±0.1 were significantly lower than those of the commercially available reference product. In addition, its formula avoids high concentrations of ethanol, PEG400 and toxic excipients such as Tween 80 and propylene glycol, fundamentally reducing the risks of vascular irritation, hemolysis and metabolism, and improving the safety of clinical use.

[0044] The present invention significantly improves the stability, safety and clinical applicability of nimodipine injection while ensuring efficient solubilization through the synergistic effect of multiple components, and has important clinical application value and market prospects. DETAILED DESCRIPTION

[0045] In order to better understand the technical solution of the present invention, the technical solution of the present invention is further described below in conjunction with specific embodiments. The embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0046] Example 1

[0047] 1. Nimodipine injection components (w / v)

[0048] Nimodipine: 0.2g

[0049] Sucrose stearate: 5g

[0050] Propylene glycol: 5g

[0051] Vitamin E TPGS: 1g

[0052] Histidine buffer: 0.1M (pH 6.5, adjusted with hydrochloric acid)

[0053] Mannitol: 40g

[0054] Water for injection: add to 1000ml

[0055] 2. Preparation process steps

[0056] (1) Preparation of histidine buffer

[0057] Weigh 2.5g of L-histidine and dissolve it in 80% of the prescribed volume of water for injection. Heat to 50±5°C and stir until completely dissolved. Adjust the pH to 6.5±0.1 with 0.1M hydrochloric acid and cool to room temperature.

[0058] (2) Preparation of nimodipine injection

[0059] In another container, add 5g of propylene glycol, slowly add 5g of sucrose stearate while stirring, and heat to 60±5°C until completely dissolved. Add 0.2g of nimodipine and continue stirring until a uniform transparent solution is formed. Add 1g of vitamin E TPGS to the transparent solution, stir and mix for 15 minutes to prepare the main drug solution, and then slowly add it to the histidine buffer, maintaining the stirring speed at 200rpm and the temperature at 40±5°C. Add 40g of mannitol and stir until completely dissolved. Add water for injection to the full amount, mix well, and then test to obtain a nimodipine solution with a pH of 6.3-6.7.

[0060] (3) Filtration and sterilization

[0061] The nimodipine solution was sterile filtered through a 0.22 μm polyethersulfone filter membrane, filled into brown ampoules or prefilled syringes according to 50 ml or required specifications, and sealed with nitrogen. Moist heat sterilization (121° C., 15 minutes) was performed, and the product 1 was packaged after cooling and labeling.

[0062] Example 2: Preparation of Nimodipine Injection with Different Excipients

[0063] Through preliminary experiments, five solubilizers were screened, and sucrose stearate showed the best overall performance in terms of critical micelle concentration and biocompatibility. Therefore, according to the method of Example 1, the amount and / or type of excipients were adjusted to prepare the injections shown in Table 1.

[0064] Table 1

[0065]

[0066]

[0067] Among them, products 8 and 9 became turbid during the liquid preparation process.

[0068] Example 3: Accelerated stability study

[0069] Products 1~7,10-13 and Accelerated stability study (40℃±2℃, RH 75%±5%) was conducted, and samples were taken at 0, 1, 2, 3, and 6 months. The test was carried out according to the method of nimodipine injection in the 2020 edition of the Chinese Pharmacopoeia. Among them, the commercially available nimodipine injection Purchased from Bayer, the ingredients are: nimodipine, ethanol, polyethylene glycol 400, sodium citrate, anhydrous citric acid, and water for injection. The inspection results are shown in Table 2.

[0070] Table 2

[0071]

[0072]

[0073]

[0074] Results Analysis and Discussion

[0075] During the six-month accelerated test, the pH of Product 1 remained consistently between 6.3 and 6.5, Impurity I was undetectable, and total impurities increased only from 0.06% to 0.18%. The drug content remained between 99.7% and 100.9%. This indicates that the histidine buffer effectively inhibited the oxidative degradation of nimodipine; sucrose stearate and vitamin E TPGS synergistically formed stable micelles, preventing drug aggregation; and mannitol regulated osmotic pressure, reducing injection pain. This excipient combination significantly enhanced the drug's physical and chemical stability.

[0076] The results of the accelerated tests of products 2 and 3 showed that the use of too low (0.3%) or too high (1.0%) sucrose stearate led to a faster increase in total impurities. For example, the total impurities of product 3 reached 0.76% after 6 months, indicating that its optimal concentration was 0.5%, but it was still better than the control group. Product 8, which replaced vitamin E TPGS with Tween 80, resulted in turbidity in the solution. Product 13, which replaced vitamin E TPGS with sodium bisulfite, failed to inhibit the formation of the oxidation product impurity I. However, Product 7 performed excellently, with the total impurity level being only 0.25% after 6 months, confirming that vitamin E TPGS itself has superior antioxidant and solubilizing effects than other antioxidants.

[0077] Product 9 uses citrate buffer instead of histidine buffer, resulting in turbidity in the solution. This indicates that histidine buffer has good compatibility with sucrose stearate and vitamin E TPGS, and there is no risk of phase separation or precipitation.

[0078] Products 10-12 replaced mannitol with glucose, lactose, and sorbitol in turn. Crystallization occurred within 2-3 months, and the total impurities increased significantly. Among them, the total impurities of product 10 reached 7.23% in 3 months, the total impurities of product 11 reached 6.17% in 2 months, and the total impurities of product 12 reached 6.25% in 2 months, indicating that mannitol is irreplaceable in maintaining drug solubility and inhibiting crystallization.

[0079] The initial total impurity was 0.13%, which rose to 0.88% after 6 months. Although the stability was better than most comparative products, it was still inferior to product 1 and product 7, and equivalent to product 2-6. In addition, no oxidation product impurity I was detected in product 2-6. The pH value dropped from 6.8 to 6.3, and the long-term degradation may be accelerated due to the oxidation of ethanol and PEG400, and high concentrations of organic solvents pose a risk of vascular irritation.

[0080] The preferred formulation of the present invention inhibits oxidative degradation and impurity formation through the synergistic action of multiple components, significantly outperforming existing commercially available products and other excipient combinations. The data from Example 3 demonstrates the critical role of optimizing the types and proportions of excipients in the stability of nimodipine injection, providing a reliable basis for the clinical application of the present invention.

[0081] Example 4: Long-term stability test

[0082] Products 1, 7 and According to the standards of the 2020 Pharmacopoeia, a 24-month long-term stability test was carried out under storage conditions of 25°C±2°C and 60%±5% relative humidity. Samples were taken and analyzed at days 0, 3, 6, 9, 12, 18, and 24. The test results are shown in Table 3.

[0083] Table 3

[0084]

[0085] Results Analysis and Discussion

[0086] Products 1 and 7 remained clear and transparent throughout the process, with no crystallization. The pH value gradually decreased from 6.5 to 6.3 and from 6.5 to 6.1, respectively, and remained in the weakly acidic range, meeting the formulation stability requirements. Impurity I was not detected, indicating that the antioxidant effect of vitamin E TPGS was effective and effectively inhibited the oxidative degradation of nimodipine. The total impurities slowly increased from 0.07% to 0.28% and from 0.08% to 0.73% within 24 months, respectively, which is far below the ≤2% impurity limit specified in the pharmacopoeia. The content decreased slightly from 99.7% to 99.1%, a decrease of only 0.6%, and from 101.9% to 100.8%, a decrease of 1.1%, indicating that the drug has excellent chemical stability.

[0087] It was clear and transparent throughout the process, but a small amount of crystallization appeared at 24 months. The pH value dropped from 6.8 to 5.8, and the acidity increased significantly, which may accelerate drug degradation. Impurity I increased from 0.02% to 1.35% within 24 months, indicating that ethanol and PEG400 could not effectively inhibit the oxidation reaction. Total impurities increased from 0.14% to 2.33%, far exceeding products 1 and 7. The content dropped from 100.3% to 98.1%, a decrease of 2.2%, indicating that drug degradation was more obvious. This shows that it relies on high concentrations of ethanol and PEG400 for solubilization, and the solvent oxidative catalytic degradation during long-term storage leads to a decrease in pH and accumulation of impurities.

[0088] The present formulation significantly inhibits the oxidative degradation and crystallization of nimodipine through the synergistic effects of histidine buffer, sucrose stearate, vitamin E TPGS, and mannitol. 24-month long-term stability data demonstrated total impurities ≤ 0.28% and a content retention rate ≥ 99.1%, confirming its reliability and safety for clinical application.

[0089] Example 5: Special safety test

[0090] To systematically evaluate the nimodipine injection (product 1, product 7) of the present invention and the commercially available reference product To determine the clinical safety differences of the drug (Bayer), special safety tests such as allergic reactions, hemolysis, and local irritation (blood vessels and muscles) were conducted in accordance with the requirements of the Good Laboratory Practice (GLP) for pharmaceutical nonclinical studies. The specific methods and results are as follows:

[0091] (1) Allergic reaction test

[0092] Rat passive skin sensitization test

[0093] Healthy SD rats were randomly divided into 6 groups (n=10). After intradermal injection of 0.1 mL of antiserum for 48 hours, the test substances were injected intravenously: product 1 (8 mg / kg, 4 mg / kg), product 7 (8 mg / kg, 4 mg / kg), (8 mg / kg, 4 mg / kg), negative control (0.9% NaCl injection), positive control (bovine serum albumin 100 mg / kg). 30 minutes after the challenge, the dorsal skin was dissected and observed for blue spot reaction as shown in Table 4.

[0094] Table 4 Allergic reaction and hemolysis test results

[0095]

[0096] Experimental results analysis and discussion

[0097] No blue spots appeared in the dosage groups of Product 1 and Product 7 and the negative control group. The diameters of the blue spots in the 8mg / kg and 4mg / kg groups were (18.5±3.2) mm and (12.1±2.9) mm, respectively, which were significantly higher than the threshold (P<0.01). The diameter of the blue spots in the positive control group was (21.8±4.1) mm. This indicates that products 1 and 7 had no passive allergic reaction. The positive reaction was dose-dependent.

[0098] Guinea pig systemic active allergy test

[0099] Healthy guinea pigs were divided into 4 groups (n=12) and injected intraperitoneally with the sensitizing dose of product 1 and product 7: 2 mg / kg; 2 mg / kg; positive control: bovine serum albumin 100 mg / kg, once every other day for 3 consecutive times. On the 13th day after the last sensitization, intravenous challenge was performed and allergic reactions within 30 minutes were observed as shown in Table 4.

[0100] Results Analysis and Discussion

[0101] In group 1, there were no allergic symptoms and the mortality rate was 0%. In group 7, two guinea pigs experienced transient tachypnea (intensity +) which recovered within 30 minutes and the mortality rate was 0%. In the positive control group, 100% of patients had severe allergic reactions with a severity of +++, including difficulty breathing and convulsions, and a mortality rate of 60%. In the positive control group, the mortality rate was 50%, and the reaction intensity was ++~++++. This shows that product 1 has the best safety, followed by product 7. High risk of allergies.

[0102] (2) Hemolysis test

[0103] Use the conventional test tube method to add 0.1-0.5mL of test product 1, product 7, The cells were incubated with 2% rabbit erythrocyte suspension at 37°C for 3 h, and hemolysis and agglutination were observed as shown in Table 4.

[0104] Results Analysis and Discussion

[0105] There was no hemolysis or agglutination in the tubes of Product 1 and Product 7 at each concentration, which was consistent with the negative control group (0.9% NaCl).

[0106] Complete hemolysis occurred within 3 hours, with a hemolysis rate of 100%, which was similar to the positive control group (distilled water). This indicates that the product of the present invention has no hemolysis risk. The hemolytic effect is significant.

[0107] (3) Rabbit vascular irritation test

[0108] The test substance was injected into the ear vein of rabbits at 1 mg / kg daily for 7 consecutive days. The rabbits were dissected 96 hours after drug withdrawal and the histopathological scores were calculated (see Table 5).

[0109] Table 5 Local irritation test scores

[0110]

[0111] Results Analysis and Discussion

[0112] Product 1 had slight edema of endothelial cells, with a score of 0.2±0.1, and no thrombosis or necrosis. The local interstitial edema was mild, with scores of 0.5±0.2 and 0.8±0.3, respectively, with occasional mononuclear cell infiltration. The negative control group scored 0.1±0.1. Low vascular irritation.

[0113] (4) Rabbit muscle irritation test

[0114] The test substance was injected into the quadriceps femoris of rabbits at a daily rate of 0.1 mg / kg for 7 consecutive days. The lesions at the injection site were evaluated 48 hours after drug withdrawal. The results are shown in Table 5.

[0115] Results and Discussion

[0116] For product 1, the local hyperemia lesion was ≤0.3×0.5cm in area, with no histological degeneration or necrosis, and a score of 0.3±0.1. For product 7, the local hyperemia lesion was ≤0.5×1.0cm in area, with mild interstitial hyperplasia, and a score of 0.7±0.2. The hyperemic lesions were ≤0.6×1.0 cm in area, with mild interstitial hyperplasia, and a score of 0.8±0.2. The negative control group had a score of 0.2±0.1. This indicates that Product 1 had minimal muscle irritation.

[0117] Test conclusion:

[0118] Product 1 and Product 7 had no passive skin allergic reaction; Product 1 had no reaction at all in the active allergy test, and Product 7 had only mild transient symptoms. Causes severe allergies and high mortality. Products 1 and 7 of the present invention have no hemolysis. The hemolysis rate was 100%. Product 1 had the lowest vascular and muscle irritation scores. This indicates that the synergistic effect of histidine buffer, sucrose stearate, vitamin E TPGS, and mannitol in the formula of the present invention can significantly improve clinical safety.

Claims

1. A nimodipine injection, characterized in that: The following components are included by weight volume percentage (w / v): Nimodipine: 0.02%; Sucrose stearate: 0.3-1.0%; Propylene glycol: 0.3-1.0%; Vitamin E TPGS: 0.05-0.2%; Histidine buffer: 0.1 M, pH 6.5 ± 0.1; Mannitol: 3.0-5.0%; Water for injection: balance.

2. The nimodipine injection according to claim 1, characterized in that The vitamin E TPGS is 0.1-0.2%.

3. The nimodipine injection according to claim 1, characterized in that The components include: Nimodipine: 0.02%; Sucrose stearate: 0.5%; Propylene glycol: 0.5%; Vitamin E TPGS: 0.1%; Histidine buffer: 0.1 M (pH 6.5 ± 0.1); Mannitol: 4.0%; Water for injection: balance.

4. The nimodipine injection according to any one of claims 1 to 3, characterized in that The histidine buffer consists of the following components (w / v): L-histidine: 0.25%; Hydrochloric acid: used to adjust pH to 6.5±0.1; Water for injection: as solvent.

5. The nimodipine injection according to any one of claims 1 to 3, characterized in that: Almost no impurity I.

6. The nimodipine injection according to any one of claims 1 to 3, characterized in that: The nimodipine injection can be stably stored for at least 2 years.

7. A method for preparing the nimodipine injection according to any one of claims 1 to 5, characterized in that: The following steps are involved: (1) Prepare histidine buffer: dissolve L-histidine in water for injection, heat and stir until dissolved, adjust the pH to 6.5 ± 0.1 with hydrochloric acid, and cool to room temperature; (2) Prepare the main drug solution: Mix propylene glycol and sucrose stearate and heat to dissolve, add nimodipine and stir until homogeneous and transparent, add vitamin E TPGS and mix; (3) Mix the main drug solution with histidine buffer, add mannitol to dissolve, and adjust the pH to 6.5 ± 0.1; (4) Sterilize by moist heat after sterilization, filtration, filling and sealing.

8. The preparation method according to claim 7, characterized in that The heating temperature in step (2) is 60±5°C, and the mixing temperature in step (3) is 40±5°C.

9. The preparation method according to claim 7, characterized in that The moist heat sterilization conditions are 121° C. and 15 minutes.

10. Use of the nimodipine injection according to any one of claims 1 to 5 in the preparation of medicaments for preventing and treating cerebrovascular diseases, migraine, sudden deafness, adjuvant treatment of Alzheimer's disease, etc.

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