Inhalation type statin preparation as well as preparation method and application thereof in treatment of lung cancer

Abstract

The invention relates to the field of biological medicine, and particularly provides an inhalation type statin preparation as well as a preparation method and application thereof in treatment of lung cancer, the inhalation type statin preparation comprises water for injection, a statin drug, a surfactant, a metal ion chelating agent, an osmotic pressure regulator, a pH buffer agent and an antioxidant; the method comprises the following steps: step 1, preparing a sterile solution A; 2, preparing a suspension B; step 3, preparing a suspension C; step 4, preparing the inhalation type statin preparation medicine preparation; the application comprises the application of the inhalation type statin preparation for treating lung cancer. According to the inhalation medicine preparation taking the statins as the unique effective component, non-invasive statin inhalation administration is realized, the local concentration of the statins in the lung is improved, the inhibition effect of the statins on lung tumors is enhanced, meanwhile, the pain of a patient in the treatment process is relieved, and the effective treatment effect of statins on the lung tumors is realized.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to an inhaled statin preparation, a preparation method thereof, and an application thereof in treating lung cancer. Background Art

[0002] Lung cancer is the most common cancer and the leading cause of cancer death worldwide.

[0003] At present, the treatment of lung cancer mainly includes multidisciplinary comprehensive treatment methods such as surgery, chemotherapy, radiotherapy and targeted therapy. Since most lung cancer patients have clinical or potential metastasis when diagnosed, which is beyond the scope of surgical resection, chemotherapy is crucial to eradicate tumor cells. The main chemotherapy drugs include: platinum drugs (cisplatin, carboplatin), antimetabolites (gemcitabine, pemetrexed), microtubule inhibitors (paclitaxel, vinblastine) and DNA topoisomerase inhibitors (irinotecan, etoposide). In addition, there are molecular targeted drugs for various lung cancer mutation targets: osimertinib and ametinib targeting EGFR sensitive gene mutations, lorlatinib and ensartinib targeting ALK fusion genes. Among them, platinum drugs are the most active anticancer agents in the clinical application of lung cancer monotherapy and combination therapy. However, during use, there are problems such as large individual differences in treatment effects, easy to develop drug resistance and systemic toxicity, which seriously limit the efficacy of the compounds and reduce the quality of life of patients.

[0004] Statins are a class of drugs that target 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and are suitable for the treatment of hyperlipidemia and hypercholesterolemia. They mainly act on the liver, have good efficacy and high safety. In addition, statins have shown certain potential in anti-tumor. However, since oral statins are affected by the first-pass elimination effect of the liver, they rarely reach the tumor site, making it difficult to implement an anti-tumor treatment regimen with statins as the only active ingredient.

[0005] In the prior art, the pharmaceutical composition of statins combined with other active ingredients shows the ability to inhibit solid tumors. In the Chinese patent with publication number CN109985242A, the application of mevalonate metabolic pathway inhibitors and alphaviruses in the preparation of anti-tumor drugs is disclosed, specifically involving a pharmaceutical composition comprising a mevalonate metabolic pathway inhibitor and alphavirus, a pharmaceutical set comprising a mevalonate metabolic pathway inhibitor and alphavirus, and the use of mevalonate metabolic pathway inhibitors and alphaviruses in the treatment of tumors, especially tumors insensitive to the alphavirus. In the Chinese patent with publication number CN118649169A, a pharmaceutical composition for the treatment of poor prognosis of endometrial cancer with fertility preservation is disclosed, specifically including a pharmaceutical composition for the treatment of poor prognosis of endometrial cancer with fertility preservation. The pharmaceutical composition provided by the present invention is composed of progestogens and statins. In the Chinese patent with publication number CN110327335A, the use of a cocrystal composed of a proton pump inhibitor and a hydroxymethylglutaryl coenzyme A reductase inhibitor in the preparation of an anti-tumor drug is disclosed. In a Chinese patent with publication number CN118924751A, the use of pitavastatin in the preparation of a drug for reducing the multidrug resistance of platinum-based chemotherapy drug-resistant tumors is disclosed; wherein, the multidrug resistance refers to the resistance of tumor patients to two or more tumor chemotherapy drugs.

[0006] The technical solution adopted by the above-mentioned patent is to combine statins with existing effective drug ingredients by designing a drug composition, and achieve combined treatment of tumors through oral or intravenous injection. The combination of multiple drugs increases the possibility of drug interactions and the risk of medication; and the administration method is affected by the liver's over-elimination effect, resulting in lower concentrations in the lesion site;

[0007] In addition, a Chinese patent with publication number CN111481670A discloses a new use of local bone injection of statins to treat tumors in mammals and human patients, using an invasive local intra-bone administration method. The invasive administration method has low patient compliance and increases patient pain. Summary of the invention

[0008] In view of the above-mentioned shortcomings of the prior art, the purpose of the present invention is to provide an inhaled statin preparation and a preparation method thereof and application in the treatment of lung cancer, so as to solve the problems of the prior art of the over-elimination effect of oral administration and the increased pain of patients by invasive administration.

[0009] To achieve the above object and other related objects, the present invention provides the following solutions:

[0010] The inhaled statin preparation comprises water for injection, a statin drug, a surfactant, a metal ion chelator, an osmotic pressure regulator, a pH buffer, and an antioxidant. The mass of the statin drug is 0.2-50.0 mg / mL, the mass of the surfactant is 0.2-10 mg / mL, the mass of the metal chelator is 0.1-10 mg / mL, the mass of the osmotic pressure regulator is 7.0-9.0 mg / mL, the pH of the pH buffer is 4-7, and the mass fraction of the antioxidant is 0.05wt%.

[0011] In one embodiment of the present invention, the statin compound includes an HMG-CoA reductase inhibitor in lactone form or carboxylic acid form, or a statin in a pharmaceutically acceptable salt form; the HMG-CoA reductase inhibitor in lactone form or carboxylic acid form includes any one of simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, pitavastatin, mevastatin, cerivastatin, dalvastatin, glenvastatin, and bervastatin; the statin in a pharmaceutically acceptable salt form includes any one of the hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate or acetate, sodium salt, potassium salt, calcium salt or magnesium salt of the statin drug.

[0012] In one embodiment of the present invention, the surfactant is selected from one or more of Tween 20, Tween 80, Span 20, Span 60, Span 80, polyoxystearate, lecithin, polyethylene glycol, polyoxyethylene castor oil, poloxamer, and sodium deoxycholate.

[0013] In one embodiment of the present invention, the metal ion chelating agent includes ethylenediaminetetraacetic acid and various salts thereof.

[0014] In one embodiment of the present invention, the osmotic pressure regulator includes one or more of sodium chloride, magnesium chloride, glycerol, mannitol, and glucose.

[0015] In one embodiment of the present invention, the pH buffer includes one or more of hydrochloric acid, sulfuric acid, sodium hydroxide, citric acid-sodium citrate buffer pair, disodium hydrogen phosphate-sodium dihydrogen phosphate buffer pair, acetic acid-sodium acetate buffer pair, citric acid-sodium citrate buffer pair, and phosphoric acid-sodium phosphate buffer pair.

[0016] In one embodiment of the present invention, the antioxidant includes any one of sodium ascorbate, sodium sulfite, and monothioglycerol.

[0017] The method for preparing an inhaled statin preparation is used to prepare the inhaled statin preparation, comprising the following steps:

[0018] Step 1: placing a metal ion chelating agent, an osmotic pressure regulator, and an antioxidant in water for injection, stirring until dissolved, and filtering the solution through a 0.22 μm membrane filter to obtain a sterile solution A;

[0019] Step 2: adding the surfactant and the micronized statin drug API to water for injection, stirring and ultrasonically dispersing, and then high-pressure homogenizing and sterilizing with high-pressure steam to obtain suspension B;

[0020] Step 3, mixing solution A and suspension B, adding water for injection to a specific value, and adding a pH adjuster to adjust the pH of the mixture to between 4 and 7 to obtain suspension C;

[0021] Step 4: Fill the suspension C into a single-dose packaging container through a sterile can to obtain an inhaled statin preparation pharmaceutical preparation.

[0022] The application of an inhaled statin preparation in treating lung cancer, wherein the inhaled statin preparation is administered to mammals by atomization inhalation through a specific atomizer device inhaler, and the dosage of the statin drug in a single inhaled statin preparation is 0.1 mg-100 mg.

[0023] In one embodiment of the present invention, the administration interval of the inhaled statin preparation is once every 1-7 days, preferably, once every two days.

[0024] As described above, the inhaled statin preparation of the present invention, its preparation method and application in treating lung cancer have the following beneficial effects:

[0025] The inhaled statin preparation provided by the present invention solves the problem of low blood concentration of statins due to the elimination effect of oral statins; inhaled administration is conducive to the enrichment of the active ingredient statin in the lungs, improving the anti-tumor effect; compared with statin injection administration, inhaled administration of statins is non-invasive, which is conducive to improving patient compliance and alleviating patient pain. In addition, the statin inhaled medical preparation shows extremely high safety during inhalation treatment; within the safe dosage range, statins have a certain inhibitory effect on lung tumors. DETAILED DESCRIPTION

[0026] The following is a description of the implementation of the present invention by means of specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification.

[0027] Inhalable statin preparations include main inhalable preparation types such as aerosols, inhalable solution preparations and inhalable dry powder preparations, preferably inhalable solution preparations and inhalable dry powder preparations.

[0028] Example 1, this example provides an inhaled statin solution preparation, including water for injection, statin, surfactant, metal ion chelator, osmotic pressure regulator, pH buffer, antioxidant, the mass of the statin is 0.2-50.0 mg / mL, the mass of the surfactant is 0.2-10 mg / mL, the mass of the metal chelator is 0.1-10 mg / mL, the mass of the osmotic pressure regulator is 7.0-9.0 mg / mL, the pH of the pH buffer is 4-7, and the mass fraction of the antioxidant is 0.05wt%. When necessary, for example, when each component has poor solubility, a cosolvent is added, and the cosolvent is dimethyl sulfoxide or ethanol, etc.

[0029] The statin compound includes a lactone form or a carboxylic acid form of an HMG-CoA reductase inhibitor, or a pharmaceutically acceptable salt form of a statin; the lactone form or the carboxylic acid form of an HMG-CoA reductase inhibitor includes any one of simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, pitavastatin, mevastatin, cerivastatin, dalvastatin, glenvastatin, and bervastatin; the pharmaceutically acceptable salt form of a statin includes any one of the hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate or acetate, sodium salt, potassium salt, calcium salt or magnesium salt of a statin drug. The surfactant is selected from one or more of Tween 20, Tween 80, Span 20, Span 60, Span 80, polyoxystearate, lecithin, polyethylene glycol, polyoxyethylene castor oil, poloxamer, and sodium deoxycholate.

[0030] The metal ion chelating agent includes ethylenediaminetetraacetic acid (EDTA) and its various salt forms, wherein the main salt forms of ethylenediaminetetraacetic acid include: ethylenediaminetetraacetic acid disodium salt (EDTA-Na2), ethylenediaminetetraacetic acid tetrasodium salt (EDTA-Na4), ethylenediaminetetraacetic acid trisodium salt, ethylenediaminetetraacetic acid dicalcium salt (EDTA-Ca2) and the like.

[0031] The osmotic pressure regulator includes one or more of sodium chloride, magnesium chloride, glycerol, mannitol, and glucose. The pH buffer includes one or more of hydrochloric acid, sulfuric acid, sodium hydroxide, citric acid-sodium citrate buffer pair, disodium hydrogen phosphate-sodium dihydrogen phosphate buffer pair, acetic acid-sodium acetate buffer pair, citric acid-sodium citrate buffer pair, and phosphoric acid-sodium phosphate buffer pair. The antioxidant includes any one of sodium ascorbate, sodium sulfite, and monothioglycerol.

[0032] Example 2: This example provides a method for preparing an inhaled statin preparation, which is used to prepare the inhaled statin preparation, comprising the following steps:

[0033] Step 1: placing a metal ion chelating agent, an osmotic pressure regulator, and an antioxidant in water for injection, stirring until dissolved, and filtering the solution through a 0.22 μm membrane filter to obtain a sterile solution A;

[0034] Step 2: Add the surfactant and the micronized statin drug API to water for injection, stir and perform ultrasonic dispersion, and then perform high-pressure homogenization and high-pressure steam sterilization to obtain suspension B; the homogenization pressure in this step is 1500 bar, the number of cycles is 3 times, the high-pressure steam sterilization temperature is 120 degrees, and the time is 15 minutes;

[0035] Step 3, mixing solution A and suspension B, adding water for injection to a specific value, where the specific value should be understood as the different types of main inhalation preparations such as aerosol, inhalation solution preparation and inhalation dry powder preparation, and the amount of water for injection is different; adding a pH adjuster to adjust the pH of the mixed solution to between 4 and 7 to obtain suspension C;

[0036] Step 4: Fill the suspension C into a single-dose packaging container through a sterile can to obtain an inhaled statin preparation pharmaceutical preparation; generally speaking, the single dose of the preparation is 0.5-10.0 mL.

[0037] Example 3: This example provides an application of an inhaled statin preparation for treating lung cancer. The composition ratio of each component of the inhaled statin preparation is as follows:

[0038] The statin drug used was pitavastatin, with a mass of 0.5 mg / mL;

[0039] The surfactant used was Tween-80, with a mass of 1.0 mg / mL;

[0040] The metal chelator used was ethylenediaminetetraacetic acid, with a mass of 0.2 mg / mL;

[0041] The osmotic pressure regulator is sodium chloride, with a mass of 9.0 mg / mL;

[0042] The pH buffer used was a citric acid-citric acid buffer pair, with a pH of 4.5;

[0043] The antioxidant is sodium ascorbate, and its mass fraction is 0.05%;

[0044] In this embodiment, the inhaled statin preparation is passed through a specific atomizer device, including Inhalers such as the above are used to administer nebulized inhalation to mammals, and the dosage of the statin drug in the inhaled statin preparation used for a single time is 0.1 mg-100 mg. The administration interval of the inhaled statin preparation is once every 1-7 days, preferably once every two days. In clinical practice, clinicians can adjust or modify the number and dosage of administration according to the needs of clinical treatment effects under the guidance of the present invention.

[0045] The inhaled statin medical preparation provided by the present invention solves the problem of too low statin blood concentration caused by the elimination effect of oral statins; inhalation administration is conducive to the enrichment of the active ingredient statin in the lungs, thereby improving the anti-tumor effect; compared with statin injection administration, inhalation administration of statins is non-invasive, which is conducive to improving patient compliance and alleviating patient pain.

[0046] Example 4, this example provides an inhaled statin dry powder preparation, the ingredients of which include: a statin drug and one or more pharmaceutically acceptable micronized carriers suitable for administration by inhalation, and additives may be added if necessary; the carrier is preferably selected from one or more of monosaccharides, disaccharides, oligosaccharides and polysaccharides, polyols, cyclodextrins, amino acids, fumaryl diketopiperazine (FDKP), dipalmitoyl phosphatidylcholine (DPPC), etc., more preferably selected from one or more of glucose, fructose, arabinose, lactose, sucrose, maltose, trehalose, dextran, dextrin, starch, cellulose, maltodextrin, sorbitol, mannitol and xylitol, and most preferably lactose. Generally, the carrier particle size distribution is: d10 = 10-160 μm, d50 = 50-250 μm, d90 = 100-350 μm. The additives include: magnesium stearate, one or more of silica gel powder and talc.

[0047] The components and their contents (by mass percentage) in the inhaled dry powder statin preparation are:

[0048] Statins: 0.01wt%-55wt%

[0049] Carrier: 45wt%-99.99wt%

[0050] Additives: 0.01wt%-1wt%

[0051] This embodiment provides a method for preparing an inhaled statin dry powder preparation, comprising the following steps:

[0052] Step 1: Micronize the statin drug. The micronization methods include: spray drying, high pressure homogenization, air flow milling and other common micronization methods. The particle size requirements of the drug after micronization are: d10 = 1.5-3.0μm, d90 ≤ 5μm;

[0053] Step 2, screening and premixing the carrier;

[0054] Step 3: Modulate the amorphous active ingredients produced from the micronized statin compound at a temperature of 25-50°C and a humidity of 50-85RH;

[0055] Step 4: Mixing the treated statin compound, carrier and additive using a high shear mixing device and / or a three-dimensional mixing device;

[0056] Step 5: Use filling equipment to load the dry powder can into the inhalation device.

[0057] The inhaled statin dry powder preparation can be administered via a specific inhalation device including The statin compound can be administered by inhalation to mammals or humans, and the dosage of the statin compound can be between 0.1 mg and 100 mg each time.

[0058] In an embodiment of the present invention, the inhalation dry powder preparation is administered to a mammal or a human by inhalation, and the administration interval of the inhalation statin dry powder preparation is once every 1-7 days, preferably, once every two days. In clinical practice, clinicians can adjust or modify the number and dosage of administration according to the needs of clinical treatment effects under the guidance of the present invention.

[0059] Example 5. This example provides Experimental Example 1: In vitro drug sensitivity test of high concentration statins on lung cancer.

[0060] An in vitro patient-derived tumor-like cell cluster (PTC) model of human lung cancer tissue was established to evaluate the effectiveness of the above-mentioned statin inhaled pharmaceutical preparations. The patient-derived lung cancer tissue was specially treated and cultured for one week to obtain a mature PTC microtumor model. The PTC microtumor was transplanted into a 96-well plate. A specific concentration of statin compounds was added to the PTC microtumor culture medium for incubation. After seven days of drug incubation, the cell survival rate of the PTC microtumor in each well was characterized by the celltiter kit. The lower the cell survival rate, the stronger the inhibitory effect of the drug on tumor growth in the well. Finally, the half-maximal inhibitory concentration (IC50) of each drug for each sample was calculated by statistically analyzing the cell survival rate of each drug at different concentrations. The lower the IC50, the stronger the inhibitory effect of the drug on this sample. Finally, the number and percentage of samples in each IC50 interval of each compound were counted. If the number of samples with IC50 in the low concentration interval is more, it means that the compound has a high efficacy against lung cancer.

[0061] The test drug groups were set up as follows: negative control group (NC), pitavastatin calcium group (Pita), atorvastatin calcium group (Ator), rosuvastatin calcium group (Rosu), simvastatin group (Sumv), and lovastatin group (Lova).

[0062] The concentrations of each dosing group were set as follows: 3.125 μM, 6.25 μM, 12.5 μM, 25.0 μM, and 50.0 μM. See Table 1 for details.

[0063]

[0064] Table 1

[0065] Experimental Example 1 shows that under high concentration conditions, the inhibition rate of statin compounds on lung cancer is relatively high, and the highest inhibition rate can reach 82.35%.

[0066] Example 6. This example provides Experimental Example 2: In vitro drug sensitivity test of low-concentration (lowest oral blood concentration) statins on lung cancer.

[0067] An in vitro patient-derived tumor-like cell cluster (PTC) model of human lung cancer tissue was established to evaluate the effectiveness of the above-mentioned statin inhaled pharmaceutical preparations.

[0068] The patient-derived lung cancer tissue was specially treated and cultured for one week to obtain a mature PTC micro-tumor model. The PTC micro-tumor was transplanted into a 96-well plate. A specific concentration of statin compounds was added to the PTC micro-tumor culture medium for incubation. After seven days of drug incubation, the cell survival rate of the PTC micro-tumor in each well was characterized by the celltiter kit. The lower the cell survival rate, the stronger the inhibitory effect of the drug on tumor growth in the well. Finally, the half inhibitory concentration (IC50) of each drug for each sample was calculated by statistically analyzing the cell survival rate of each drug at different concentrations. The lower the IC50, the stronger the inhibitory effect of the drug on this sample. Finally, the number and percentage of samples in each IC50 interval of each compound were counted. If the number of samples with IC50 in the low concentration interval is more, it means that the compound has a high efficacy against lung cancer.

[0069] The test drug groups were set up as follows: negative control group (NC), pitavastatin calcium group (Pita), atorvastatin calcium group (Ator), rosuvastatin calcium group (Rosu), simvastatin group (Sumv), and lovastatin group (Lova).

[0070] Concentration settings for each dosing group:

[0071] Pitavastatin calcium group: 48.8nM, 97.7nM, 195.3nM, 781.2nM, 3.125μM.

[0072] Atorvastatin calcium group: 195.3nM, 781.2nM, 3.125μM, 6.25μM, 12.5μM.

[0073] Rosuvastatin calcium group: 195.3nM, 781.2nM, 3.125μM, 6.25μM, 12.5μM.

[0074] Simvastatin group: 195.3nM, 781.2nM, 3.125μM, 6.25μM, 12.5μM.

[0075] Lovastatin group: 195.3 nM, 781.2 nM, 3.125 μM, 6.25 μM, 12.5 μM. See Table 2 for details.

[0076]

[0077] Table 2

[0078] Experimental Example 2 shows that the inhibition rate of statins on lung cancer is low at the blood drug concentration when taking statins orally, which reflects the necessity of increasing the local concentration around lung tumors for the inhibition effect on lung cancer by administering the drug by pulmonary inhalation.

[0079] Example 7. This example provides Experimental Example 3: Safety evaluation of pulmonary administration of statin inhaled pharmaceutical preparations to mice.

[0080] A total of 260 normal mice (half of which were male and half were female) were required for the experiment. They were divided into 13 groups according to Table 3, with 20 mice in each group (10 of which were female and 10 were male); according to the final drug concentration in Table 3, mice in each group were treated with the mouse lung atomizer. The final drug volume for each mouse was 50 μL, the drug frequency was once every 2 days, and the treatment cycle was 14 days.

[0081]

[0082] Table 3

[0083] The survival of mice was monitored every day, and the survival curve and body weight changes of mice were calculated.

[0084] After 14 days of continuous administration, tissues including lung, liver, heart, and kidney were fixed and sliced ​​for HE staining.

[0085] The results of Experimental Example 3 show that within the test concentration range, the pharmaceutical preparation of the statin compound has no obvious toxicity.

[0086] The experiments in the above-mentioned Test Examples 1, 2 and 3 have proved that the statin inhalation preparation provided by the present invention, rather than oral statin drugs, has a significant therapeutic effect of inhibiting the growth of lung tumors.

[0087] In summary, the inhalation pharmaceutical preparation of the present invention, which uses statin as the only active ingredient, realizes non-invasive inhalation administration of statin, increases the local concentration of statin in the lungs, enhances its inhibitory effect on lung tumors, and at the same time alleviates the pain of patients during treatment, and realizes the effective therapeutic effect of statins on lung tumors; and the statin inhalation medical preparation shows extremely high safety during inhalation treatment; within the safe dosage range, statin has a certain inhibitory effect on lung tumors. Therefore, the present invention effectively overcomes various shortcomings in the prior art and has a high industrial utilization value.

[0088] The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. Anyone familiar with the art may modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by a person of ordinary skill in the art without departing from the spirit and technical concept disclosed by the present invention shall still be covered by the claims of the present invention.

Claims

1. An inhaled statin preparation, characterized in that: The invention comprises water for injection, a statin, a surfactant, a metal ion chelating agent, an osmotic pressure regulator, a pH buffer and an antioxidant. The mass of the statin is 0.2-50.0 mg / mL, the mass of the surfactant is 0.2-10 mg / mL, the mass of the metal chelating agent is 0.1-10 mg / mL, the mass of the osmotic pressure regulator is 7.0-9.0 mg / mL, the pH value of the pH buffer is 4-7, and the mass fraction of the antioxidant is 0.05wt%.

2. The inhaled statin preparation according to claim 1, characterized in that: The statin compound includes an HMG-CoA reductase inhibitor in lactone form or carboxylic acid form, or a statin in a pharmaceutically acceptable salt form; the HMG-CoA reductase inhibitor in lactone form or carboxylic acid form includes any one of simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, pitavastatin, mevastatin, cerivastatin, dalvastatin, glenvastatin, and bervastatin; the statin in a pharmaceutically acceptable salt form includes any one of the hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate or acetate, sodium salt, potassium salt, calcium salt or magnesium salt of the statin drug.

3. The inhaled statin preparation according to claim 1, characterized in that: The surfactant is selected from one or more of Tween 20, Tween 80, Span 20, Span 60, Span 80, polyoxystearate, lecithin, polyethylene glycol, polyoxyethylene castor oil, poloxamer, and sodium deoxycholate.

4. The inhaled statin preparation according to claim 1, characterized in that: The metal ion chelating agent includes ethylenediaminetetraacetic acid and its various salt forms.

5. The inhaled statin preparation according to claim 1, characterized in that: The osmotic pressure regulator includes one or more of sodium chloride, magnesium chloride, glycerol, mannitol, and glucose.

6. The inhaled statin preparation according to claim 1, characterized in that: The pH buffer includes one or more of hydrochloric acid, sulfuric acid, sodium hydroxide, citric acid-sodium citrate buffer pair, disodium hydrogen phosphate-sodium dihydrogen phosphate buffer pair, acetic acid-sodium acetate buffer pair, citric acid-sodium citrate buffer pair, and phosphoric acid-sodium phosphate buffer pair.

7. The inhaled statin preparation according to claim 1, characterized in that: The antioxidant includes any one of sodium ascorbate, sodium sulfite and monothioglycerol.

8. A method for preparing an inhalable statin preparation, for preparing the inhalable statin preparation according to any one of claims 1 to 7, characterized in that: The steps include: Step 1: placing a metal ion chelating agent, an osmotic pressure regulator, and an antioxidant in water for injection, stirring until dissolved, and filtering the solution through a 0.22 μm membrane filter to obtain a sterile solution A; Step 2: adding the surfactant and the micronized statin drug API to water for injection, stirring and ultrasonically dispersing, and then high-pressure homogenizing and sterilizing with high-pressure steam to obtain suspension B; Step 3, mixing solution A and suspension B, adding water for injection to a specific value, and adding a pH adjuster to adjust the pH of the mixture to between 4 and 7 to obtain suspension C; Step 4: Fill the suspension C into a single-dose packaging container through a sterile can to obtain an inhaled statin preparation pharmaceutical preparation.

9. Use of an inhaled statin preparation for treating lung cancer, characterized in that: The inhaled statin preparation is administered to mammals by atomization inhalation through a specific atomizer device inhaler, and the dosage of the statin drug in a single inhaled statin preparation is 0.1 mg-100 mg.

10. The use of the inhaled statin preparation for treating lung cancer according to claim 9, characterized in that: The inhaled statin preparation is administered once every 1-7 days, preferably once every two days.

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