Slow-release type chlorsulfuron nano preparation and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations and preparation thereof, and discloses a sustained-release type chlorsulfuron nano preparation, and every 100 g of the preparation comprises the following components by weight: 0.1 to 5.0 g of chlorsulfuron, 0.5 to 3.5 g of myristyl alcohol, 3.0 to 9.0 g of fir oil, 1.0 to 5.0 g of ethyl acetate, 3.0 to 6.0 g of polyoxyethylene (2) oleyl alcohol ether, 8.0 to 20.0 g of tween-20, 1.0 to 2.0 g of xylitol, 0.01 to 0.1 g of triethanolamine, and the balance of water for injection. After intramuscular injection, the medicine is slowly released in a tissue local part, a long-acting effect can be achieved, the administration frequency is reduced, and the animal stress reaction is reduced. And meanwhile, the particle size of the medicine is distributed at a nanometer level, so that the bioavailability is greatly improved. The invention further discloses a preparation method, and the preparation method does not need special equipment, can be converted in a common workshop, and has a wide market prospect.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations and preparation thereof, and particularly relates to a sustained-release clorsulon nano preparation and a preparation method thereof. Background Art

[0002] Trematodes are a common name for animals of the class Trematodes, belonging to the phylum Platyhelminthes. They primarily parasitize the digestive tract, blood, liver, mesenteric veins, kidneys, and subcutaneous tissue. After infecting an animal, trematodes require nutrients for their own reproduction and growth, which come directly from the animal's body and ultimately from feed. This reduces the animal's feed conversion rate, increases the feed-to-meat ratio, and prolongs the time it takes to reach market. Furthermore, as worm-like organisms, trematodes can physically damage infected tissues during their activity, leading to local inflammatory reactions. The excretions of some trematodes are irritating and toxic, further exacerbating the inflammatory response. Infected organs can become red, swollen, hot, painful, and dysfunctional, ultimately impacting production performance. Furthermore, trematode-infected animals can harbor trematodes in their organs and tissues, seriously impacting food safety after slaughter and marketing. Some species are even zoonotic, impacting consumer health.

[0003] Currently, there are numerous commercially available anti-trematode drugs, including albendazole, praziquantel, and closantel. These drugs were highly effective in their early stages, but after decades of continuous use, resistance has emerged in many areas. Even with rotational, combined, and increased dosage regimens, some farms still cannot achieve complete decontamination. The market needs new anti-trematode drugs to meet this clinical need. Furthermore, due to their unique structures, albendazole and praziquantel are currently only available in oral formulations, such as tablets, powders, and suspensions. Oral formulations require intestinal absorption, and some of the drug is ultimately excreted in the feces, resulting in less than 100% bioavailability compared to injectable formulations. While an injectable formulation of closantel is available, its tissue concentration is low after administration, with the majority bound to plasma proteins in the blood, making it less effective against parasites present in tissues. In view of the current problems faced by this type of drug, the market urgently needs a drug category that is non-resistant, can be injected, and can remain in the tissue for a long time after use, achieving a long-term and efficient trematode killing effect to make up for the shortcomings of existing technology.

[0004] In response to the defects of the existing technology and the clinical needs of the market, the present invention uses the new broad-spectrum veterinary anti-trematode drug clorsulon as the main ingredient, and prepares it into a sustained-release injectable nanoformulation, which solves the problem of high drug resistance faced by the drug market of this category. It can also use the sustained-release characteristics of the dosage form to make the drug exert its efficacy in the body for a longer time, retain it in the tissues for a longer time, achieve optimal bioavailability, and ensure that the parasites in the animal body are expelled and killed more thoroughly. Summary of the Invention

[0005] The purpose of the present invention is to provide a sustained-release clorsulon nanoformulation, and providing a preparation method thereof is the second purpose of the present invention.

[0006] Based on the above purpose, the present invention adopts the following technical scheme: a sustained-release clorsulon nanoformulation, wherein per 100g of the preparation, the weight composition is: clorsulon 0.1-5.0g, myristyl alcohol 0.5-3.5g, fir oil 3.0-9.0g, ethyl acetate 1.0-5.0g, polyoxyethylene (2) oleyl ether 3.0-6.0g, Tween-20 8.0-20.0g, xylitol 1.0-2.0g, triethanolamine 0.01-0.1g, and the balance is water for injection.

[0007] Preferably, the weight composition of each 100g of the nano preparation is: clorsulon 1.0-4.0g, myristyl alcohol 0.8-3.2g, fir oil 4.0-8.0g, ethyl acetate 1.5-4.5g, polyoxyethylene (2) oleyl ether 3.5-5.5g, Tween-20 10.0-18.0g, xylitol 1.2-1.8g, triethanolamine 0.02-0.08g, and the balance is water for injection.

[0008] Further preferably, the weight composition of each 100g of the nanoformulation is: 2.5g of clorsulon, 2.0g of myristyl alcohol, 6.0g of fir oil, 3.0g of ethyl acetate, 4.5g of polyoxyethylene (2) oleyl ether, 14.0g of Tween-20, 1.5g of xylitol, 0.05g of triethanolamine, and 66.45g of water for injection.

[0009] Preferably, the preparation has a sustained-release and long-acting characteristic.

[0010] Preferably, the drug particle size distribution of the preparation is between 5.0 and 900.0 nm.

[0011] The preparation method of the sustained-release clorsulon nanoformulation comprises the following steps:

[0012] (a) First, mix fir oil and ethyl acetate, then add myristyl alcohol and clorsulon respectively and stir to dissolve, add polyoxyethylene (2) oleyl ether and stir to mix after the system is uniform, then slowly add water for injection while ultrasonic emulsification, and stop adding water after the system turns into a milky white or light yellow opaque viscous liquid to obtain system 1;

[0013] (b) Tween-20 and the remaining amount of water for injection were mixed and gradually added to System 1 while homogenizing and emulsifying. The system gradually changed from milky white or light yellow opaque to light yellow transparent, and then changed again to milky white or light yellow opaque. The system also changed from a viscous state to a thin state with good fluidity, thereby obtaining System 2;

[0014] (c) Xylitol and triethanolamine are added to system 2 and mixed, and the mixture is aseptically packaged to obtain the sustained-release clorsulon nanoparticle preparation product of the present invention.

[0015] The invention has a reasonable formulation, and the final preparation is a milky white or light yellow opaque liquid (such as Figure 1 , Example 1), can be diluted with water according to market specifications and content needs, the diluted system remains uniform, and there will be no unstable conditions such as drug precipitation, stratification and phase transition (such as Figure 4 ). Observed under an electron microscope, the drug is spherical or quasi-spherical, and is adhered or wrapped by a sustained-release colloid (such as Figure 2 , Example 1). The specific particle size range was analyzed using a laser particle size analyzer, and the drug particle size distribution was between 5.0 and 900.0 nm (such as Figure 3 , Example 1).

[0016] The sustained-release clorsulon nanoformulation of the present invention slowly releases the drug after intramuscular injection, achieving a long-lasting effect. It also prevents redness, swelling, pustules, or nodules at the injection site, demonstrating excellent safety. The drug particles are nanometer-sized, have a large specific surface area, and offer strong permeability, resulting in higher clinical bioavailability and significantly superior efficacy to conventional formulations.

[0017] In the prescription of the present invention, the effects of each component are as follows:

[0018] 1) The selected clorsulon is a new anti-trematode drug that can solve the problem of parasite insensitivity caused by the emergence of drug resistance in existing commercial anti-trematode drugs, and its control effect is significantly better than traditional anti-trematode drugs;

[0019] 2) A mixture of fir oil and ethyl acetate was selected as the solvent for clorsulon. This combination maximizes the solubility of clorsulon, thereby increasing the drug loading of the final formulation. Furthermore, the resulting mixture exhibits excellent long-term storage stability at temperatures between -20°C and 40°C, making it suitable for the natural environments of most regions in China and facilitating clinical application.

[0020] 3) Myristyl alcohol is selected as an ingredient in the present invention because it can delay the release of clorsulon in tissues, thereby achieving a sustained-release, long-lasting effect, helping to reduce the number of dosing times and extend the drug's shelf life. Furthermore, compared with other conventional sustained-release materials, myristyl alcohol can effectively help enhance the needle-penetrating properties of the drug solution (Comparative Example 1), thereby facilitating clinical injection administration procedures.

[0021] 4) Polyoxyethylene (2) oleyl alcohol ether is selected as the component of the present invention because the surfactant has good compatibility with the mixed phase formed by fir oil and ethyl acetate. Whether it is ultrasonic emulsification or homogeneous emulsification, it can better emulsify the drug into spheres and maintain good stability;

[0022] 5) Tween-20 is selected as the component of the present invention because it can help enhance the sustained release effect of the system and also maintain the final system more stable.

[0023] 6) The combination of xylitol and triethanolamine is selected as the components of the system of the present invention. Firstly, it helps form a buffer system, thereby maintaining the stability of the final formulation. If it is removed, the system is prone to instability problems such as discoloration, stratification, and drug precipitation (Comparative Example 2). Secondly, it is less likely to form pustules, nodules, hemolysis, and inflammatory reactions at the injection site after clinical use.

[0024] The present invention needs to be injected clinically. If the dosage of a single site is too small and exceeds the minimum range of the syringe and cannot be operated, it can also be further diluted with water for injection before injection. The diluted liquid will not show unstable phenomena such as stratification, demulsification, precipitation, discoloration, etc. The sample of Example 1 was used as a test sample. After it was diluted with water for injection by 2 times, 5 times, 10 times and 100 times respectively, it was placed at room temperature for 8 hours for observation. The results are as follows: Figure 4 As shown, it shows that the system has good stability after dilution and can ensure uniform clinical drug delivery.

[0025] Compared with the prior art, the present invention achieves the following technical effects through improvements in formulation and process:

[0026] (1) The present invention prepares a novel clorsulon preparation, which provides a new anti-trematode drug category for veterinary clinics. Compared with other categories, it has a stronger killing effect on trematodes and has no drug resistance. It is suitable for animal groups that have developed drug resistance due to long-term use of traditional drugs, resulting in drug insensitivity, filling a gap in the domestic market;

[0027] (2) The clorsulon preparation of the present invention is a sustained-release, long-acting type, which can reduce the number of administrations in clinical use. At the same time, after injection, the drug has sufficient time to diffuse throughout the body through the bloodstream, making it more effective against parasitic insects in tissues and killing insects more thoroughly.

[0028] (3) The particle size of the clorsulon drug of the present invention is distributed at the nanometer level, with a large specific surface area, making it easier to enter tissues and having higher bioavailability;

[0029] (4) The preparation of the present invention can be further diluted with water before use, and the diluted system still maintains good stability;

[0030] (5) The preparation process of the present invention is highly operable and does not require special production equipment, which is conducive to large-scale production transformation and market promotion of drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is a photograph of the appearance of the sustained-release clorsulon nanoformulation prepared in Example 1 of the present invention;

[0032] Figure 2 This is a transmission electron microscope photograph of the sustained-release clorsulon nanoformulation prepared in Example 1 of the present invention;

[0033] Figure 3 This is the laser particle size scanning distribution of the sustained-release clorsulon nanoformulation prepared in Example 1 of the present invention;

[0034] Figure 4 These are photos of the appearance of the sustained-release clorsulon nanoformulation prepared in Example 1 of the present invention after being diluted with 2-fold, 5-fold, 10-fold and 100-fold water, respectively. DETAILED DESCRIPTION

[0035] The present invention will be further described below by way of specific examples, but these specific embodiments do not limit the scope of protection of the present invention in any way.

[0036] Examples 1-10

[0037] To simplify the description, the weight composition of the sustained-release clorsulon nanoformulations of the present invention described in Examples 1-10 is given below in the form of a table, as shown in Table 1.

[0038] Table 1 Weight composition per 100g of the present invention in Examples 1-10

[0039]

[0040] The sustained-release clorsulon nanoformulation described in Example 1 is prepared by the following steps:

[0041] (a) Mix 6.0 g of fir oil and 3.0 g of ethyl acetate, then add 2.0 g of myristyl alcohol and 2.5 g of clorsulon and stir to dissolve. After the system is homogeneous, add 4.5 g of polyoxyethylene (2) oleyl alcohol and stir. Then gradually add some water for injection while ultrasonic emulsification. At this time, the system will change from clear and transparent to milky white and opaque, and the properties will become viscous. When the viscosity reaches the optimal state, stop adding water. At this time, the amount of water added is 21.5 g, and System 1 is obtained.

[0042] (b) 14.0 g of Tween-20 and the balance 44.95 g of water for injection were mixed and gradually added to System 1 while homogenizing and emulsifying the system. During the entire process, the system gradually changed from milky white opaque to light yellow transparent, and then changed again to milky white opaque. The system also gradually changed from a viscous state to a thin state with good fluidity, thereby obtaining System 2;

[0043] (c) 1.5 g of xylitol and 0.05 g of triethanolamine were added to system 2, mixed evenly, and aseptically packaged to obtain the sustained-release clorsulon nanoformulation of Example 1 of the present invention.

[0044] The preparation methods of Examples 2 to 10 are the same as those of Example 1, except that the compositions of the clorsulon nanoformulations are different.

[0045] Comparative Example 1: Selection test of myristyl alcohol as the sustained-release material of the present invention

[0046] For verifying that myristyl alcohol is the best choice of sustained-release material of the present invention, the inventor sets 5 groups of tests with reference to the prescription and preparation technology of embodiment 1, and compares and evaluates by the needle-passing property test commonly used by injection.The 1st group is embodiment 1 of the present invention, and strictly prepares sample according to prescription and process.The 2nd group is after myristyl alcohol component is removed (spare amount is supplemented with water for injection), and the sample prepared is as blank control.The 3rd, 4th, 5th groups are respectively cellulose acetate, sodium carboxymethyl cellulose and polyvidone groups, and with reference to embodiment 1 prescription, replace equal amount of myristyl alcohol with cellulose acetate, sodium carboxymethyl cellulose and polyvidone respectively, and preparation technology is identical with embodiment 1 (wherein sodium carboxymethyl cellulose and polyvidone are dissolved in water for injection and prepare, thereby obtain sustained-release system).The sample prepared by each group is carried out needle-passing property test respectively, and specific grammar is as follows.

[0047] Needle-through test: Vacuum-draw the solution using a commercially available 1.0ml syringe. The time required to draw out 1.0ml was calculated. Each sample group underwent three draws, and the average was taken for comparison. The results are shown in the table below.

[0048] Table 2 Comparative results of needle-passing test of sustained-release clorsulon nanoparticle preparation of the present invention

[0049]

[0050] As shown in Table 2, the time required to draw out 1.0 ml of the sample prepared in Example 1 in Group 1 was significantly shorter than that in the other groups, indicating that the use of myristyl alcohol as a sustained-release material can enhance the permeability of the drug solution, and the effect is significantly better than that of other sustained-release materials, and is also better than that of the group without myristyl alcohol.

[0051] The results show that myristyl alcohol is the best sustained-release material for the sustained-release clorsulon nanoformulation of the present invention. Comparative Example 2: Effect of xylitol and triethanolamine system on the stability of the present invention

[0052] The buffer system composed of xylitol and triethanolamine plays a significant role in maintaining the stability of the present invention and is an essential component of the present invention. The inventors used the formulation and preparation method of Example 1 as a reference and prepared the sample from Example 1, designated Sample 1. Subsequently, the xylitol and triethanolamine were removed, and the remainder was supplemented with water for injection, resulting in a system designated Sample 2. Simultaneously, the xylitol and triethanolamine were replaced with a conventional phosphate buffer system (1.9734 g disodium hydrogen phosphate and 0.2245 g potassium dihydrogen phosphate, dissolved in sterile water for injection to a 1000 mL solution, and the pH adjusted to 7.35), producing Sample 3. Finally, the three samples were placed in a constant temperature and humidity environment at 40°C and 70% relative humidity for accelerated stability testing. Samples were taken and observed on the 7th, 15th, 30th, 60th, 90th, and 180th day of testing to observe any instability, such as discoloration, stratification, or precipitation. The results are shown in the table below.

[0053] Table 3 Effect of xylitol and triethanolamine system on the stability of the present invention

[0054]

[0055] Table 3 shows that, in the absence of xylitol and triethanolamine, sample 2 began to show system instability on day 60, with stratification and drug precipitation. This stratification became more pronounced by day 180, with significant drug precipitation. Sample 3, after replacing the phosphate buffer with saline, began to show color change and instability on day 30. Finally, after day 180, the sample turned brown, with significant stratification and significant drug precipitation.

[0056] The results show that xylitol and triethanolamine are essential ingredients of the present invention and can significantly enhance the stability of the drug.

[0057] Test Example 1: Characteristics of the sustained-release clorsulon nanoformulation of the present invention

[0058] In order to observe the microscopic state of the sustained-release nanosystem of the present invention, the clorsulon sample prepared in Example 1 was dripped onto the surface of the detection copper mesh, negatively stained with phosphotungstic acid, and dried naturally under light-proof conditions. The transmission electron microscope was used for observation. The results are shown in FIG. Figure 2 Then it was diluted 50 times with deionized water and scanned by laser particle size analyzer. The particle size distribution is shown as follows. Figure 3 shown.

[0059] Depend on Figure 2It can be seen that the clorsulon drug particles are spherical or quasi-spherical, with particle sizes distributed at the nanometer level, and are wrapped or adhered by sustained-release materials.

[0060] Depend on Figure 3 It can be seen that the particle size distribution of the clorsulon drug of the present invention is between 5.0 and 900.0 nm.

[0061] The results show that the present invention meets the characteristics of sustained release and nano preparation.

[0062] Test Example 2 Stability test of the drug of the present invention

[0063] Samples of Examples 1-10 of the present invention were sampled and subjected to high temperature, room temperature, refrigerated, and frozen stability tests according to the methods specified in veterinary drug standards. Each sample was placed in a constant temperature environment of 40°C, room temperature of 25°C, constant temperature of 4°C, and constant temperature of -20°C. Samples were taken and observed 7 days, 15 days, 1 month, 3 months, 6 months, and 12 months after the start of the test, and the results were recorded.

[0064] Test results: No discoloration, stratification, drug precipitation, phase transition or other unstable phenomena occurred in the samples kept at constant temperature of 40℃, room temperature of 25℃, constant temperature of 4℃ and constant temperature of -20℃.

[0065] The results show that the sustained-release clorsulon nanoformulation of the present invention has good stability.

[0066] Test Example 3 Safety Test

[0067] In same sheep farm, select 80 of same batch Boer goats of 4 months age, be randomly divided into 4 groups, often organize 20, male and female half and half.Wherein, the 1st group is control group, and every sheep is according to 0.1ml / kg body weight intramuscular injection normal saline, the 2nd, 3rd, 4th groups are low, medium and high dose groups (taking the sample prepared by embodiment 1 as example) of the present invention, and every sheep is according to the sustained release clorsulon nano injection prepared by 0.05ml / kg, 0.1ml / kg and 0.2ml / kg intramuscular injection of the present invention.Each group of sheep is managed by same breeder, and is cultured in same environment, during every day medication 1 time, continuous use 7 days, observes the behavior performance of each group of sheep, record picking food, drinking water and death situation, injection site is observed simultaneously, see whether the situations such as redness and swelling, suppuration, tubercle occur, thus judge safety of the present invention.If there is sheep to occur death in process of the test, then dissect on the spot, observe the pathological condition of each internal organ, and record.

[0068] Results: All test groups exhibited healthy behavior, including normal feeding and drinking habits. Other behavioral changes were similar to those in the control group, and no sheep died. Observation of the injection site revealed no redness, swelling, suppuration, or nodules, demonstrating good drug-tissue compatibility.

[0069] The results show that the sustained-release clorsulon nanoformulation of the present invention has good safety.

[0070] Test Example 4 Clinical efficacy test

[0071] The study was conducted at a small-tailed Han sheep farm in northern Henan Province, where schistosomiasis was a serious problem. The disease was widespread and rapidly spreading. The affected sheep showed lethargy, pale or yellow conjunctivae, anemia, swelling of the jaw or neck, stunted growth, dull coats, poor feeding and water intake, and often lay alone in a corner. Fifty sick sheep with similar disease severity were selected from a flock and randomly divided into five groups of 10 each. Group 1 was a control group that did not receive any drug treatment and was allowed to develop the disease. Group 2 was a clorsulon conventional preparation group (clorsulon was dissolved in a system consisting of fir oil, ethyl acetate, DMSO, and 1,2-propylene glycol to prepare a 2.5% solution). Each sheep was treated with a 0.1 ml / kg intramuscular injection of the neck. Group 3 was a sustained-release clorsulon nanoformulation group (treated with the sample prepared in Example 1). Each sheep was treated with a 0.1 ml / kg intramuscular injection of the neck. Group 4 was an albendazole treatment group. Each sheep was orally administered albendazole tablets at 15 mg / kg body weight. Group 5 was a praziquantel group. Each sheep was orally administered praziquantel tablets at 20 mg / kg body weight. Each group of sheep was treated once on the day of the experiment and then observed for two consecutive weeks. The improvement of clinical symptoms, feed intake, and water intake were recorded. If any sheep died during the experiment, they were dissected on site to observe the lesions of various organs and the infection of trematodes, and detailed records were made according to the scoring criteria. The results are shown in Table 4.

[0072] Judging criteria:

[0073] Death: If the disease of sick sheep worsens due to trematode infection during the test and eventually dies, -1 point will be recorded;

[0074] Ineffective: Although the sick sheep survived the test, the clinical manifestations did not improve significantly, and the score was 0;

[0075] Outcome: During the trial, the symptoms of the sick sheep were significantly alleviated and improved compared to before the medication, but there was still a gap compared to the healthy sheep, and they were not fully recovered, so 1 point was recorded;

[0076] Recovery: During the test period, the symptoms of fluke infection in sick sheep completely disappear, and their behavior is no different from that of healthy sheep of the same age. The disease is completely recovered and scored 2 points;

[0077] Cure rate: refers to the ratio of the number of cured test sheep to the total number of test sheep in the group × 100%;

[0078] Total effective rate: refers to the ratio of the number of test sheep that have recovered and recovered to the total number of test sheep in this group × 100%.

[0079] Table 4 Clinical efficacy test of the sustained-release clorsulon nanoformulation of the present invention

[0080]

[0081] The test results are analyzed as follows:

[0082] 1. In Group 1, without drug treatment, the mortality rate of sick sheep reached 40%, resulting in a score of -4. However, in Groups 2, 3, 4, and 5, which underwent drug treatment, the cure rates were 40%, 90%, 30%, and 40%, respectively, with overall efficacy rates reaching 70%, 100%, 50%, and 60%, respectively. This indicates that the selected drugs have a therapeutic effect on schistosomiasis.

[0083] 2. Although both groups received the same dose of clorsulon, Group 3 had a 50% and 30% higher cure rate and overall efficacy rate, respectively, and a score 9 points higher. This suggests that the combined use of sustained-release and nanoformulation technology in Group 3 significantly enhanced the overall bioavailability of the drug and its efficacy.

[0084] 3. Compared with Group 3, Groups 4 and 5 had cure rates 60% and 50% lower, respectively, and overall efficacy rates 50% and 40% lower, respectively, resulting in scores 13 and 12 points lower. This suggests that the parasites in the field have developed a degree of resistance to traditional drugs (albendazole and praziquantel). Treatment with the new drug clorsulon has improved efficacy.

[0085] The results show that the sustained-release clorsulon nanoformulation of the present invention has an ideal effect in treating schistosoma japonicum infection, and the drug efficacy is maintained for a longer time, the therapeutic effect is better, and there is no drug resistance.

Claims

1. A sustained-release clorsulon nanoparticle preparation, characterized in that: The weight composition of each 100g of the preparation is: 0.1-5.0g of clorsulon, 0.5-3.5g of myristyl alcohol, 3.0-9.0g of fir oil, 1.0-5.0g of ethyl acetate, 3.0-6.0g of polyoxyethylene (2) oleyl alcohol ether, 8.0-20.0g of Tween-20, 1.0-2.0g of xylitol, 0.01-0.1g of triethanolamine, and the balance is water for injection.

2. The sustained-release clorsulon nanoparticle preparation according to claim 1, characterized in that: The weight composition of each 100g of the preparation is: 1.0-4.0g of clorsulon, 0.8-3.2g of myristyl alcohol, 4.0-8.0g of fir oil, 1.5-4.5g of ethyl acetate, 3.5-5.5g of polyoxyethylene (2) oleyl alcohol ether, 10.0-18.0g of Tween-20, 1.2-1.8g of xylitol, 0.02-0.08g of triethanolamine, and the balance is water for injection.

3. The sustained-release clorsulon nanoparticle preparation according to claim 2, characterized in that: The weight composition of each 100g of the preparation is: 2.5g of clorsulon, 2.0g of myristyl alcohol, 6.0g of fir oil, 3.0g of ethyl acetate, 4.5g of polyoxyethylene (2) oleyl alcohol ether, 14.0g of Tween-20, 1.5g of xylitol, 0.05g of triethanolamine, and 66.45g of water for injection.

4. The sustained-release clorsulon nanoparticle preparation according to claim 3, characterized in that: The preparation has the characteristics of sustained release and long-acting effect.

5. The sustained-release clorsulon nanoparticle preparation according to claim 4, characterized in that: The drug particle size distribution of the preparation is between 5.0 and 900.0 nm.

6. The method for preparing the sustained-release clorsulon nanoformulation according to any one of claims 1 to 4, characterized in that: The following steps are involved: (a) First, mix fir oil and ethyl acetate, then add myristyl alcohol and clorsulon respectively, stir and dissolve, add polyoxyethylene (2) oleyl alcohol ether after the system is uniform, stir and mix, then add water for injection, add while ultrasonic emulsification, stop adding water after the system turns into milky white or light yellow opaque viscous liquid, and obtain system 1; (b) Tween-20 and the remaining amount of water for injection are mixed and gradually added to system 1, and homogenization and emulsification are performed while adding. The system gradually changes from milky white or light yellow opaque to light yellow transparent, and then changes again to milky white or light yellow opaque. The system also changes from a viscous state to a thin state with good fluidity, thereby obtaining system 2; (c) xylitol and triethanolamine are added into system 2 and mixed, and aseptically packaged to obtain the sustained-release clorsulon nanoparticle preparation product of the present invention.

Images