Buparvaquone nano preparation and preparation method thereof

Abstract

The invention discloses a buparvaquone nano preparation and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations, the active ingredient of the buparvaquone nano preparation is buparvaquone, and every 100g of the buparvaquone nano preparation contains 0.1-3.0 g of buparvaquone, 4.0-8.0 g of caraway oil, 1.0-3.0 g of ethyl oleate, 8.0-12.0 g of glyceryl tristearate, 3.0-5.0 g of lecithin, 1.0-6.0 g of oleyl alcohol, 0.1-1.0 g of anhydrous magnesium chloride and the balance of ethyl caprate. The preparation is a non-aqueous preparation and can play a quick-acting and long-acting role after being injected, drug particles exist in the form of nanospheres, the particle size is distributed between 5.0 nm and 100.0 nm, the bioavailability is high, clinical use is safe, drug resistance does not exist, production is easy to convert, the clinical treatment effect on babesiella bovis infection is remarkably superior to that of the prior art, and the market prospect is good.

Description

Technical Field

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

[0002] Bovine pyrocystis is a common protozoan parasitic disease in veterinary clinics. The parasites mainly parasitize in the blood of cattle and have a strong destructive effect on red blood cells. After a large number of red blood cells are damaged, the bilirubin released exceeds the normal metabolic level of the body, causing cattle to be infected and show symptoms of yellowing of the whole body, especially the visible mucous membranes, tears, urine, saliva, feces, etc., and liver function will also be abnormal. When the sick cattle are not treated for a long time, the body will develop anemia due to insufficient normal red blood cells, the systemic transport of oxygen will be impaired, and the cell metabolism level will decrease, and then show more serious systemic symptoms, including decreased feed intake, lack of energy, increased body temperature, slowed growth, etc. The disease is mainly spread through surface blood-sucking parasites (ticks, etc.) as a medium. It is mainly local epidemic, with a high incidence in summer and autumn, and often occurs in cattle farms with poor environmental sanitation, high breeding density and low management level. Once cattle are infected, the mortality rate can reach more than 60%. Even if they can survive in the end, it will affect the growth rate in the later stage, resulting in an increase in feed-to-meat ratio and a decrease in breeding rewards.

[0003] Clinically, drugs such as triazoguanidine, doxycycline, oxytetracycline, and imidazopyrim are generally used to treat bovine pyrophagoides. However, due to long-term use, these drugs have developed drug resistance in many areas. In order to achieve the desired effect, farms have to increase the dosage and extend the treatment time, but this will cause excessive drug residues in the body and change the metabolic law, further causing the withdrawal period to become inaccurate. There is a risk of excessive drug residues after cattle are slaughtered and put on the market, posing a threat to food safety. Therefore, the market urgently needs a new drug to fill the gap. Under the premise of meeting food safety requirements, it can achieve the effect of killing pyrophagoides through conventional dosage and treatment.

[0004] Bupavaquin is an aromatic organic compound with a six-carbon cyclic dione structure containing two double bonds. It has good thermal stability and chemical stability, has good inhibitory and killing effects on pyrosomes, and can be used to treat ruminant pyrosome infections. However, Bupavaquin has poor water solubility and is difficult to dissolve in local tissue fluid and plasma after intramuscular injection, resulting in long-term failure of blood drug concentration to reach the peak. At the same time, the effective blood drug concentration is also short-lived, which directly limits the application of the drug in veterinary clinics. In addition, since most cattle infected with pyrosomes are acute, it is necessary to fully exert the efficacy of the drug in a short period of time to control the disease in time, which places high requirements on the "fast-acting" nature of the dosage form. At the same time, in order to ensure that there will be no repeated infection within an epidemic cycle after the worms are killed, to minimize the number of treatments and to extend the effective period of treatment, requirements are also put forward for the "long-acting" nature of the dosage form.

[0005] In view of the above situation, a new dosage form of bupavaquine with both rapid and long-acting effect is needed in the market. Summary of the invention

[0006] The purpose of the present invention is to provide a bupavaquin nano-preparation, and providing a preparation method thereof is the second purpose of the present invention.

[0007] Based on the above invention objectives, the present invention adopts the following technical solutions:

[0008] The invention discloses a bupavaquin nano preparation. The weight composition of each 100g of the preparation is as follows: 0.1-3.0g of bupavaquin, 4.0-8.0g of caraway seed oil, 1.0-3.0g of ethyl oleate, 8.0-12.0g of glyceryl tristearate, 3.0-5.0g of lecithin, 1.0-6.0g of oleyl alcohol, 0.1-1.0g of anhydrous magnesium chloride, and the balance is ethyl caprate.

[0009] Preferably, the weight composition of each 100g of the preparation is: 0.5-2.5g of bupavaquinone, 5.0-7.0g of caraway oil, 1.5-2.5g of ethyl oleate, 9.0-11.0g of glyceryl tristearate, 3.5-4.5g of lecithin, 2.0-5.0g of oleyl alcohol, 0.3-0.7g of anhydrous magnesium chloride, and the balance is ethyl caprate.

[0010] More preferably, 1.5 g of bupavaquinone, 6.0 g of caraway oil, 2.0 g of ethyl oleate, 10.0 g of glyceryl tristearate, 4.0 g of lecithin, 3.5 g of oleyl alcohol, 0.5 g of anhydrous magnesium chloride, and 72.5 g of ethyl caprate are used.

[0011] The bupavaquinone nano preparation is a non-aqueous preparation.

[0012] The drug of the bupavaquin nano preparation exists in the form of nanospheres, and the particle size distribution is between 5.0 and 100.0 nm.

[0013] The method for preparing a bupavaquinone nano-preparation comprises the following steps:

[0014] a) mixing caraway oil and ethyl oleate and heating to 72-78° C., adding bupavaquinone and stirring to dissolve, to obtain system 1; taking anhydrous ethanol 3-5 times the weight of glyceryl tristearate, heating to 72-78° C., adding glyceryl tristearate and stirring to dissolve, and then mixing the dissolved solution with system 1 to obtain system 2;

[0015] b) adding lecithin to system 2 and mixing, while stirring and cooling, the appearance changes from clear and transparent to translucent, and then changes to opaque after cooling to room temperature, adding oleyl alcohol and mixing evenly to obtain system 3; adding ethyl caprate to system 3, the system changes from opaque to translucent, and obtains system 4;

[0016] c) adding anhydrous magnesium chloride into system 4 to dissolve, and then drying in vacuum, and waiting for ethanol to completely evaporate to a constant weight, to obtain the bupavaquinone nano-preparation of the present invention.

[0017] The present invention prepares bupavaquin into nanospheres through technical improvement, and the drug particle size distribution is between 5.0 and 100.0 nm, the specific surface area is large, and after intramuscular injection, it can be quickly distributed throughout the body through the blood flow, thereby killing the pyrozoa in the blood. At the same time, with the help of drug excipients, a temporary "drug depot" can be formed at the injection site, and a long-term effect can be achieved through slow release, thereby helping to reduce the number of drug administrations, reduce animal stress reactions, and save manpower, material resources and financial resources. In addition, compared with the prior art, the bupavaquin nano preparation of the present invention does not have drug resistance, has a better effect on the prevention and control of bovine pyrozoa, and has a better market application prospect.

[0018] In the prescription of the present invention, bupavaquin is the main component, and the others are auxiliary components. The functions of each auxiliary component are:

[0019] 1) Caraway oil and ethyl oleate are selected as the ingredients of the present invention. Through laboratory testing and evaluation, this combination has a greater solubility for bupavaquinone, which can significantly increase the drug loading to meet clinical needs, while also maintaining the stability of the final system at different storage temperatures. In addition, these two excipients are easy to purchase and have standardized drug excipient quality standards. They can be quality controlled before production conversion to ensure smooth production;

[0020] 2) Glyceryl tristearate is selected as the component of the present invention because it has good compatibility with caraway oil and ethyl oleate, and is easily soluble in hot ethanol but difficult to dissolve in cold ethanol, so that the purpose of coating the main component can be achieved by adjusting the system temperature.

[0021] 3) Lecithin is selected as the component of the present invention because it can help the drug particles to be closer to spherical during the cooling process of the system in step b), and the specific surface area can be maximized, so that the overall bioavailability of the drug is higher.

[0022] 4) Oleyl alcohol is selected as the component of the present invention because it can maintain the stability of the system. If it is removed, the coated drug particles will rupture and lose the sustained release effect (Comparative Example 1).

[0023] 5) Anhydrous magnesium chloride is selected as the component of the present invention because it can prevent the precipitation of bupavaquinone under low-temperature storage conditions. Once the drug is precipitated, it cannot be dissolved again even if the room temperature is restored or the system is heated again, thus affecting clinical use (Comparative Example 2).

[0024] Compared with the prior art, the technical effects of the present invention are:

[0025] 1. The drug particle size distribution of the present invention is at the nanometer level, the drug particles have a large specific surface area, and have high bioavailability. After injection, they can quickly enter the plasma and diffuse throughout the body through the bloodstream, which can quickly kill the infected pyrodiids in the blood. It has the characteristics of rapid effect and high insecticidal efficiency. For cattle pyrodiid disease characterized by "rapid onset" and "high mortality rate", it can quickly improve symptoms and reduce mortality rate;

[0026] 2. After use, the present invention can form a temporary "drug depot" at the injection site, and the drug is slowly released into the peripheral tissue, thereby achieving a long-term effect. Clinically, it can reduce the number of drug administrations, reduce animal stress reactions, and save manpower, material resources, and financial resources. Generally, repeated infection can be avoided without secondary administration within an epidemic cycle, while the prior art often requires repeated administration within an epidemic cycle to achieve the effect of avoiding recurrence;

[0027] 3. The bupavaquin nanoformulation of the present invention has no drug resistance, and the conventional dose and normal course of treatment can achieve the desired effect. Even if the recommended dosage is halved, the clinical efficacy requirements can be met (Experimental Example 3). This shows that the technology of the present invention improves the drug bioavailability of bupavaquin, and there is no need to increase the dose and extend the course of treatment during clinical use, which is conducive to controlling drug residues and ensuring the food safety of beef after cattle are slaughtered and put on the market;

[0028] 4. The final system of the present invention is a non-aqueous preparation system. The drug has good stability in an organic environment. After intramuscular injection into the tissue, although it mixes with aqueous body fluids, the drug particles can still maintain their original shape and nanoscale size characteristics, which is conducive to fully exerting the drug effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is the appearance of the bupavaquin nanoformulation of the present invention (Example 1);

[0030] Figure 2 is a transmission electron microscope field of view of the present invention (Example 1);

[0031] Figure 3 It is a transmission electron microscope image of the sample of the present invention (Example 1) after adding water. DETAILED DESCRIPTION

[0032] The present invention will be specifically described below by way of examples, but these specific embodiments do not limit the protection scope of the present invention in any way.

[0033] Examples 1-10

[0034] To make the specification concise, the weight compositions of the bupavaquinone nanoformulations of Examples 1-10 are given in table form below, as shown in Table 1.

[0035] Table 1 Composition of each component of Examples 1-10 (total 100 g)

[0036]

[0037] Example 1 A method for preparing a bupavaquinone nanoformulation comprises the following steps:

[0038] a) 6.0 g of caraway oil and 2.0 g of ethyl oleate were mixed evenly, the mixture was heated to 75° C., 1.5 g of bupavaquin raw material was added and stirred to dissolve, and the temperature was maintained unchanged to obtain system 1. 40.0 g of anhydrous ethanol was taken and heated to 75° C., 10.0 g of glyceryl tristearate was added and stirred to dissolve to obtain an ethanol solution thereof, and the solution was mixed with system 1 to obtain system 2;

[0039] b) 4.0 g of lecithin was added to system 2, and the system was cooled while stirring, and the system changed from clear and transparent to translucent, and finally became opaque when cooled to room temperature, and 3.5 g of oleyl alcohol was added and mixed evenly to obtain system 3. Then 72.5 g of ethyl caprate was slowly added to system 3, and the system changed from opaque to translucent, and system 4 was obtained;

[0040] c) 0.5 g of anhydrous magnesium chloride is added to system 4 to dissolve, and the system is placed in a vacuum drying oven for vacuum decompression treatment (the anhydrous ethanol therein will evaporate quickly), and after the system has constant weight, the bupavaquinone nano-preparation of the present invention is obtained.

[0041] In other embodiments, the preparation of the present invention can be achieved by heating the mixture of caraway oil and ethyl oleate that meets step a) to 72-78° C., and heating anhydrous ethanol to 72-78° C.

[0042] In other embodiments, the preparation of the present invention can be achieved when the amount of anhydrous ethanol in step a) is 3 to 5 times the weight of glyceryl tristearate.

[0043] The bupavaquin nanoformulations and preparation methods thereof of Examples 2 to 10 are the same as those of Example 1, except that the compositions of the preparations are different, as shown in Table 1.

[0044] Comparative Example 1 Effect of oleyl alcohol on the stability of the present invention

[0045] Oleyl alcohol plays an important role in the stability of the system of the present invention. Removal of oleyl alcohol will cause the drug particles to break and affect the efficacy. With reference to the formulation and preparation process of Example 1, oleyl alcohol is not added to the system, and the balance is supplemented with ethyl caprate. The prepared sample and the sample with oleyl alcohol added in Example 1 are placed in a drug accelerated stability box at a temperature of 40°C and a relative humidity of 70% at the same time for stability investigation. Observations were made at 1d, 15d, 30d, 60d, 90d and 180d after the start of the test to determine the effect of oleyl alcohol on the stability of the present invention. The results are shown in Table 2.

[0046] Table 2 Observation of the effect of oleyl alcohol on the stability of the system of the present invention

[0047] Inspection time Samples with oleyl alcohol removed Sample with added oleyl alcohol (Example 1) 1d Yellow translucent, good fluidity Yellow translucent, good fluidity 15d Yellow translucent, good fluidity Yellow translucent, good fluidity 30d Yellow translucent, poor fluidity Yellow translucent, good fluidity Chapter 60d Yellow opaque, poor fluidity Yellow translucent, good fluidity Chapter 90d Light brown opaque, poor fluidity Yellow translucent, good fluidity Chapter 180d Brown opaque, poor fluidity Yellow translucent, good fluidity

[0048] It can be seen from the table that after the removal of oleyl alcohol, under the accelerated environment of high temperature and high humidity, the fluidity began to deteriorate on the 30th day, and the appearance changed from translucent to opaque on the 60th day, and the fluidity deteriorated. Until the end of the test, the appearance changed from yellow to brown, the fluidity decreased, and the system was unstable. However, under the same conditions, the sample prepared in Example 1 always maintained a yellow translucent appearance and good fluidity.

[0049] The results show that oleyl alcohol is an essential component of the present invention and plays an important role in maintaining the stability of the system.

[0050] Comparative Example 2 Effect of anhydrous magnesium chloride on low temperature storage of the present invention

[0051] Anhydrous magnesium chloride is an essential component of the present invention, and can inhibit the precipitation of the main component parvaquinone under low temperature. The inventor still used the formula and preparation method of Example 1 as a reference to conduct experiments. In step c), anhydrous magnesium chloride was not added to system 4, but system 4 was directly subjected to vacuum decompression treatment. After constant weight, the obtained sample and the sample prepared in Example 1 were placed in 4°C and -20°C environments at the same time, and observed at the 1st, 15th, 30th, 60th, 90th and 180th day after the start of the experiment, so as to judge the influence of anhydrous magnesium chloride on the drug. The results are shown in Table 3.

[0052] Table 3 Effect of anhydrous magnesium chloride on low temperature storage of the drug of the present invention

[0053]

[0054]

[0055] It can be seen from Table 3 that after removing anhydrous magnesium chloride, the low temperature resistance of the system deteriorates. Drug precipitation begins at 60 days under 4°C refrigeration conditions and at 30 days under -20°C conditions. The lower the temperature, the greater the amount of drug precipitation.

[0056] The results show that anhydrous magnesium chloride can enhance the low-temperature storage stability of the system of the present invention and is an essential component.

[0057] Comparative Example 3 Effect of the Presence of Water on the System of the Invention

[0058] The present invention is a pure organic system, belonging to a non-aqueous preparation. After contacting water, the aqueous system and the organic system have poor mutual solubility, but the drug particles will not break and can maintain their original shape (spherical or quasi-spherical). The sample prepared in Example 1 of the present invention was added with deionized water in a ratio of 2:1 (Example 1: deionized water = 2:1), shaken and placed at room temperature for 30 minutes, and then observed by electron microscope. The results are as follows Figure 3 shown.

[0059] It can be seen from the figure that: 1. The water area and organic area in the system are unevenly distributed; 2. The drug particles can maintain their original shape (spherical or quasi-spherical).

[0060] The results show that: 1. The final system of the present invention is unstable when it comes into contact with water, so the present invention must be a non-aqueous preparation; 2. After intramuscular injection, the drug particles of the present invention are mixed with aqueous body fluids such as tissue fluid and plasma, and can still maintain their original shape without rupture, have good stability, and will not affect the pharmacokinetic characteristics.

[0061] Experimental Example 1 Stability Study of the Present Invention

[0062] The samples of the bupavaquin nanoformulation prepared in Examples 1-10 were evaluated at different temperatures according to the pharmaceutical stability requirements. The temperatures for investigation were -20°C, 4°C, 25°C and 40°C, and each group of samples was packaged in a transparent ampoule bottle. The number of samples investigated at different temperatures for each example was 10, thereby minimizing the experimental error. The day the test started was the first day, and samples were taken and investigated at the 15th day, 30th day, 60th day, 90th day and 180th day to see if there was any unstable situation such as precipitation, discoloration, stratification, coagulation, etc.

[0063] Test results: The properties of all samples remained stable during the test period, and the drugs showed no precipitation, discoloration, stratification or coagulation.

[0064] The results show that the bupavaquin nanoformulation of the present invention has good stability.

[0065] Experimental Example 2 Safety Test

[0066] The inventor selected 40 healthy Simmental beef cattle weighing about 200kg for safety assessment. These test cattle were randomly divided into 4 groups, 10 in each group, half male and half female. Wherein the first group was the control group, each neck muscle was injected with normal saline, and the second, third and fourth groups were respectively low, medium and high dose test groups of the present invention, and each cattle was injected with 1.25mg / kg, 2.5mg / kg and 5.0mg / kg doses of bupavaquin into the neck muscle of each cattle (taking Example 1 as an example), and the bupavaquin nano preparation of the present invention was injected ..., and the bupavaquin nano preparation of the present invention was injected into the neck muscle, and the bupavaquin nano preparation of the present invention was injected into the neck muscle, and the bupavaquin nano preparation of the present invention was injected into the neck muscle, and the bupavaquin

[0067] Test results: No deaths occurred in any group of cattle during the test period. The behavior of cattle in the test and control groups was the same, their eating and drinking were normal, and there was no redness, swelling, suppuration or nodules at the injection site.

[0068] The results show that the bupavaquin nanoformulation of the present invention has good safety.

[0069] Experimental Example 3: Drug Efficacy Test

[0070] To illustrate the effect of the present invention, the following efficacy test was conducted by taking the bupavaquin preparation sample prepared in Example 1 as an example.

[0071] The inventor selected 30 sick cows weighing about 300kg and with similar disease severity at a Simmental beef cattle fattening farm in Henan where pyrophagoides is prevalent, and randomly divided them into 6 groups, 5 in each group. Group 1 is a control group, which does not use any drugs and allows the disease to develop. Group 2 is a bupavaquin nano preparation group of the present invention, and each cow is measured by bupavaquin, and the bupavaquin nano preparation of the present invention (sample of Example 1) is injected intramuscularly at a dose of 2.5mg / kg body weight, and the first day of medication is 1 time. Group 3 is also a bupavaquin nano preparation group of the present invention, and each cow is measured by bupavaquin, and the bupavaquin nano preparation of the present invention (sample of Example 1) is injected intramuscularly at a dose of 1.25mg / kg body weight, and the first day of medication is 1 time. The fourth group is the common preparation group of bupavaquin. Bupavaquin is prepared into a 1.5% injection solution with organic solvent (containing 25% N-methylpyrrolidone, 10% 1,2-propylene glycol, 35% polyethylene glycol 200, 3% polyvinylpyrrolidone K30, 1% Tween 80, 1.5% bupavaquin, and the balance is glycerol formal). Each cow is calculated as bupavaquin, and a one-time intramuscular injection is given at a dose of 2.5 mg / kg. The medication can be used once on the first day. The fifth group is the same therapeutic drug triazoline group. Each cow is given a dose of 5 mg / kg body weight. Triazoline is prepared into a 7% solution with injection water and then injected intramuscularly. The medication is used once a day according to the standard for 3 consecutive days. The sixth group is the same therapeutic drug oxytetracycline group. Each cow is given an intramuscular injection of oxytetracycline injection at a dose of 10 mg / kg body weight. The medication is used once a day according to the standard usage for 3 consecutive days. During the treatment period, the cattle in each group were kept in the same environment and managed by the same breeder. The inventor observed the clinical manifestations of the cattle in each group every day, and recorded the feed intake, water intake, body temperature and death. The results are shown in Table 4.

[0072] Table 4 Results of the drug efficacy test of bupavaquinone of the present invention

[0073]

[0074]

[0075] Comparative analysis of results:

[0076] 1) Two pigs died in the control group of group 1 without any drug treatment. No deaths occurred in the experimental groups 2, 3, 4, 5 and 6 after treatment, and the average daily feed intake and water intake of each experimental group increased significantly compared with the control group during the treatment period, indicating that bupavaquin, triazoline and oxytetracycline have a therapeutic effect on this disease;

[0077] 2) Compared with Group 3 and Group 4, all three groups were treated with bupavaquin. When the dosage and number of medications were the same for Group 2 and Group 4, the body temperature of Group 2 returned to normal on the second day after medication, and did not rise again until the end of the experiment, and the food intake and water intake also returned to normal. Although the body temperature, food intake and water intake of Group 4 also returned to normal on the second day of medication, the body temperature rose again to above 40°C on the third day, and the food intake and water intake decreased again compared with the second day. It shows that the bupavaquin preparation of the present invention has a sustained-release long-acting effect, and the drug effect lasts longer; compared with Group 2 and Group 3, when the dosage of Group 3 was halved, the final drug effect of Group 3 was basically the same, indicating that after the present invention prepares bupavaquin into a nano preparation, the bioavailability is improved, the dosage is smaller, the drug residue will become lower, and the food safety requirements are better met.

[0078] 3) Compared with Group 2 and Group 5, although both groups had returned to normal eating and drinking on the second day of medication, and their body temperature did not rise again after the end of the experiment, Group 5 needed to take the medication three times in a row to achieve the effect, while the present invention only needed to take the medication once to achieve the treatment requirements. In comparison, the clinical use of the present invention is more convenient and labor-saving, and the restraint stress response to cattle during the medication process is also smaller (Note: when injecting the medication, the cattle need to be caught and restrained before the medication is given to avoid the needle running away during the resistance and struggle of the cattle, and the restraint injection process will produce a greater stress response to the cattle);

[0079] 4) Compared with Group 2 and Group 6, the body temperature of Group 6 was always higher (>39.5°C), and the cattle were in a continuous fever state, indicating that the infected parasites had developed resistance to conventional doses of oxytetracycline, while Group 2 achieved the ideal therapeutic effect after only one use of the drug, indicating that the present invention has no drug resistance and a better therapeutic effect.

[0080] The results show that the bupavaquinone nano-preparation of the present invention has an ideal therapeutic effect on bovine pyrophagoides, has a sustained-release and long-acting effect, requires fewer medication times, has a higher drug bioavailability, and has no drug resistance.

Claims

1. A bupavaquin nanoformulation, characterized in that: Every 100g of the invention contains 0.1-3.0g of bupavaquinone, 4.0-8.0g of caraway oil, 1.0-3.0g of ethyl oleate, 8.0-12.0g of glyceryl tristearate, 3.0-5.0g of lecithin, 1.0-6.0g of oleyl alcohol, 0.1-1.0g of anhydrous magnesium chloride, and the balance is ethyl caprate.

2. The bupavaquinone nanoformulation according to claim 1, characterized in that: Every 100g of the invention contains 0.5-2.5g of buparvaquinone, 5.0-7.0g of caraway oil, 1.5-2.5g of ethyl oleate, 9.0-11.0g of glyceryl tristearate, 3.5-4.5g of lecithin, 2.0-5.0g of oleyl alcohol, 0.3-0.7g of anhydrous magnesium chloride, and the balance is ethyl caprate.

3. The bupavaquinone nanoformulation according to claim 2, characterized in that: Bupavaquin 1.5 g, caraway oil 6.0 g, ethyl oleate 2.0 g, glyceryl tristearate 10.0 g, lecithin 4.0 g, oleyl alcohol 3.5 g, anhydrous magnesium chloride 0.5 g, ethyl caprate 72.5 g.

4. The bupavaquinone nanoformulation according to any one of claims 1 to 4, characterized in that: The magnesium chloride is anhydrous magnesium chloride.

5. The bupavaquinone nanoformulation according to any one of claims 1 to 4, characterized in that: This preparation is a non-aqueous preparation.

6. The bupavaquinone nanoformulation according to any one of claims 1 to 4, characterized in that: The drug particles exist in the form of nanospheres, and the particle size distribution is between 5.0 and 100.0 nm.

7. The method for preparing the bupavaquin nanoformulation according to any one of claims 1 to 4, characterized in that: The following steps are involved: a) mixing caraway oil and ethyl oleate and heating to 72-78° C., adding bupavaquinone and stirring to dissolve, to obtain system 1; taking anhydrous ethanol 3-5 times the weight of glyceryl tristearate, heating to 72-78° C., adding glyceryl tristearate and stirring to dissolve, and then mixing the dissolved solution with system 1 to obtain system 2; b) adding lecithin to system 2 and mixing, while stirring and cooling, the appearance changes from clear and transparent to translucent, and then changes to opaque after cooling to room temperature, adding oleyl alcohol and mixing evenly to obtain system 3; adding ethyl caprate to system 3, the system changes from opaque to translucent, and obtains system 4; c) adding anhydrous magnesium chloride into system 4 to dissolve, and then drying in vacuum, and waiting for ethanol to completely evaporate to a constant weight, to obtain the bupavaquinone nano-preparation of the present invention.

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