A kind of fluorouracil nanostructure lipid carrier and preparation method thereof

Abstract

The present application discloses a flurana nanostructured lipid carrier and a preparation method thereof, which belongs to the technical field of insecticide preparation. The flurana nanostructured lipid carrier semisolid cream can be administered orally or externally, and is used for preventing and treating ectoparasitic diseases of pets such as dogs and cats. The present application improves the performance of the nanostructured lipid carrier by adding a quantitative polyol to the aqueous phase and compounding with lipids, which not only makes the nanostructured lipid carrier system more stable and has a high encapsulation rate, but also improves the release and absorption of the main drug in the nanostructured lipid carrier, solves the solubility of flurana, and improves the bioavailability, promotes the drug to better exert its therapeutic effect in the body, enables pets to improve the therapeutic effect while reducing the dosage of the drug, improves the safety of the drug, reduces the damage to the pet, and has significant clinical application value.

Description

Technical Field

[0001] The present application belongs to the technical field of insecticide preparation, and in particular relates to a flurella nanostructured lipid carrier and a preparation method thereof. Background Art

[0002] Fluoranab is a broad-spectrum, long-acting external anthelmintic of the isoxazoline class, which shows a good killing effect on parasites such as ticks, siphonaptera, pedicels, hemiptera and diptera. It is widely used in the prevention and treatment of external parasitic diseases of pets such as dogs and cats, and has a good market prospect. The veterinary dosage forms of fluoranab currently circulating on the market mainly include chewable tablets, drops and solution for poultry. However, on the one hand, the solubility of fluoranab in water is low, which limits its application. On the other hand, the oral and dermal administration of fluoranab chewable tablets and drops for dogs and cats has low bioavailability and low utilization efficiency. Major research and development institutions are all trying to solve the corresponding problems. For example, patent CN118477183A uses cyclodextrin inclusion to solve the solubility problem and prepares soluble powder for poultry; patent CN118121716A also uses cyclodextrin inclusion to prepare highly water-soluble powder; patent CN118059039A and patent CN118477040A prepare a flurella solution. Although the above patents have solved the problem of low solubility of flurella to varying degrees, they have not solved the problem of low bioavailability of flurella.

[0003] As drug carriers, liposomes have complex production methods and require the use of organic solvents, have low drug encapsulation efficiency, low bioavailability, and are difficult to scale up. Nanostructured lipid carriers (NLCs) have a structure similar to liposomes, but different components and functions. In the structure of nanostructured lipid carriers, not all lipid nanoparticles have a continuous bilayer. Some lipid nanoparticles are micellar structures that encapsulate drug molecules in a non-aqueous core, making them exhibit better physical stability than liposomes. In addition, due to the lower solid-state molecular fluidity of NLC, the effective release of loaded drugs can be more accurately controlled. In summary, compared with traditional liposomes, NLCs are simple to prepare, do not require the use of organic solvents, have higher loading capacity and higher bioavailability, and are easy to mass produce. Summary of the invention

[0004] The purpose of the embodiments of the present application is to provide a flurella nanostructured lipid carrier and a preparation method thereof, so as to solve the technical problems of low solubility and low bioavailability of flurella in the prior art.

[0005] To achieve the above-mentioned purpose, the technical solution adopted in the present application is: to provide a method for preparing a flurella nanostructured lipid carrier, which specifically comprises the following steps:

[0006] (i) Preparation of oil phase: melt the main emulsifier, lipid and flurellanine in a water bath to prepare the oil phase standby solution;

[0007] (ii) Preparation of aqueous phase: swell and mix the attractant, emulsifier, polyol and water in a water bath to obtain an aqueous phase standby solution;

[0008] (III) Preparation of colostrum: adding the oil phase reserve solution to the water phase reserve solution, shearing to form a primary mixed solution, homogenizing and circulating the primary mixed solution to obtain colostrum; cooling the colostrum to obtain a flurella nanostructured lipid carrier in the form of a semisolid cream;

[0009] The lipids in step (i) include liquid lipids and solid lipids, and the mass ratio of the liquid lipids to the solid lipids is 5-7:3-5. Preferably, the mass ratio of the liquid lipids to the solid lipids is 6:4.

[0010] In one embodiment,

[0011] The temperature of the water bath in step (i) and step (ii) is 50-80°C, preferably, the temperature of the water bath is 60°C.

[0012] In one embodiment,

[0013] In step (i), the main emulsifier is Tween 20 or Tween 80, preferably, the main emulsifier is Tween 80; in step (ii), the auxiliary emulsifier is poloxamer 188 or poloxamer 407, preferably, the auxiliary emulsifier is poloxamer 188.

[0014] In one embodiment,

[0015] The mass ratio of the primary emulsifier to the auxiliary emulsifier is 1-1.5: 1-1.5, preferably, the mass ratio of the primary emulsifier to the auxiliary emulsifier is 1.5: 1.

[0016] In one embodiment,

[0017] The liquid lipid is one of oleic acid, ethyl acetate, epoxidized soybean oil, isopropyl myristate, triolein or castor oil, and preferably, the liquid lipid is ethyl acetate; the solid lipid is one of distearic acid glyceryl, palmitic acid, stearic acid, lauric acid, behenic acid glyceryl or monostearic acid glyceryl, and preferably, the solid lipid is monostearic acid glyceryl.

[0018] In one embodiment,

[0019] In step (ii), the polyol is one of propylene glycol, glycerol, polyethylene glycol 200 or polyethylene glycol 400. Preferably, the polyol is propylene glycol.

[0020] In one embodiment,

[0021] The mass ratio of the polyol to the lipid is 0.75-2: 1-3, preferably, the mass ratio of the polyol to the lipid is 1: 1.

[0022] In one embodiment,

[0023] The appetite attractant in step (ii) is one of barbecue flavor, chicken liver flavor or beef flavor, and the colostrum in step (iii) is cooled to room temperature after being prepared.

[0024] The present application also provides a flurana nanostructured lipid carrier, which is a flurana nanostructured lipid carrier prepared according to the preparation method of a flurana nanostructured lipid carrier described in any of the above embodiments, and the composition of the flurana nanostructured lipid carrier is as follows: every 100 g of the flurana nanostructured lipid carrier contains 0.1-10 g of flurana, 20 g of lipid, 8 g of emulsifier, 0.1 g of attractant, 20 g of polyol, and the balance is water.

[0025] The present application provides a method for preparing a flurana nanostructured lipid carrier, and provides a flurana nanostructured lipid carrier semisolid cream, which can be administered orally or externally, and is used to prevent and treat ectoparasitic diseases of pets such as dogs and cats; the present application not only improves the performance of the nanostructured lipid carrier by adding a quantitative polyol to the aqueous phase and compounding with lipids, so that the main drug in the nanostructured lipid carrier is more evenly distributed, the system is more stable, and the encapsulation rate is high, but also improves the release and absorption of the main drug in the nanostructured lipid carrier, solves the solubility of flurana, and improves the oral bioavailability, promotes the drug to better exert its therapeutic effect in the body, enables pets to improve the therapeutic effect while reducing the dosage of the drug, improves the safety of the drug, reduces damage to the pet, and has significant clinical application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0027] Figure 1 is the in vitro release curve;

[0028] Figure 2 It is a drug-time curve diagram. DETAILED DESCRIPTION

[0029] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present application more clear, the present application is further described in detail. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0030] Example 1

[0031] A method for preparing a flurellane nanostructured lipid carrier comprises the following steps:

[0032] (I) Preparation of oil phase: Tween 20, oleic acid, distearic acid glyceryl and flurellanine were heated and melted in a water bath at 60°C to prepare an oil phase standby solution; the lipids were oleic acid and distearic acid glyceryl mixed in a ratio of 6:4;

[0033] (II) Preparation of aqueous phase: swell and mix the barbecue flavor, poloxamer 188, polyethylene glycol 200 and water in a 60°C water bath to prepare an aqueous phase standby solution; the mass ratio of Tween 20 to poloxamer 188 is 1.5:1; the mass ratio of polyethylene glycol 200 to lipid is 1:1;

[0034] (III) Preparation of colostrum: Add the oil phase reserve solution into the water phase reserve solution, and use a high shear instrument to high-speed shear for 5 min at 11000 rpm to form a primary mixed solution, and homogenize the primary mixed solution with a high-pressure homogenizer at a pressure of 500 bar for 3 times to obtain colostrum; cool the colostrum to room temperature to obtain the flurella nanostructured lipid carrier, which is in the form of a semi-solid cream.

[0035] Example 2

[0036] The difference between this example and Example 1 is that the temperature of the water bath in step (i) and step (ii) is 50° C. The other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0037] Example 3

[0038] The difference between this example and Example 1 is that the temperature of the water bath in step (i) and step (ii) is 80° C. The other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0039] Example 4

[0040] The difference between this embodiment and embodiment 1 is that oleic acid and distearic acid glyceryl are mixed in a ratio of 5:5, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0041] Example 5

[0042] The difference between this example and Example 1 is that oleic acid and distearic acid glyceryl are mixed in a ratio of 7:3, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0043] Example 6

[0044] The difference between this example and Example 1 is that the lipids are ethyl acetate and stearic acid, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0045] Example 7

[0046] The difference between this example and Example 1 is that the lipids are epoxidized soybean oil and stearic acid, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0047] Example 8

[0048] The difference between this embodiment and embodiment 1 is that the lipids are isopropyl myristate and lauric acid, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0049] Example 9

[0050] The difference between this embodiment and embodiment 1 is that the lipids are triolein and behenic acid glyceryl, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0051] Example 10

[0052] The difference between this example and Example 1 is that the lipids are castor oil and glyceryl monostearate, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0053] Embodiment 11

[0054] The difference between this example and Example 1 is that the mass ratio of Tween 20 to Poloxamer 188 is 1:1, and the other operations are the same to prepare the flurella nanostructured lipid carrier.

[0055] Example 12

[0056] The difference between this example and Example 1 is that the mass ratio of Tween 20 to Poloxamer 188 is 1:1.5, and the other operations are the same to prepare the flurella nanostructured lipid carrier.

[0057] Example 13

[0058] The difference between this embodiment and embodiment 1 is that the main emulsifier is Tween 80, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0059] Embodiment 14

[0060] The difference between this embodiment and embodiment 1 is that the co-emulsifier is poloxamer 407, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0061] Embodiment 15

[0062] The difference between this example and Example 1 is that the mass ratio of polyethylene glycol 200 to lipid is 0.75:1, and the other operations are the same to prepare the flurella nanostructured lipid carrier.

[0063] Example 16

[0064] The difference between this example and Example 1 is that the mass ratio of polyethylene glycol 200 to lipid is 2:3, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0065] Embodiment 17

[0066] The difference between this embodiment and embodiment 1 is that the polyol is propylene glycol, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0067] Embodiment 18

[0068] The difference between this embodiment and embodiment 1 is that the polyol is propylene glycol, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0069] Embodiment 19

[0070] The difference between this embodiment and embodiment 1 is that the polyol is polyethylene glycol 400, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0071] Embodiment 20

[0072] The difference between this embodiment and embodiment 1 is that the attractant is chicken liver flavor essence, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0073] Embodiment 21

[0074] The difference between this embodiment and embodiment 1 is that the appetite attractant is beef flavor essence, and the other operations are the same to prepare the flurellane nanostructured lipid carrier.

[0075] A flurella nanostructured lipid carrier, comprising the following ingredients: per 100 g of the flurella nanostructured lipid carrier, 0.1-10 g of flurella, 20 g of lipid, 8 g of emulsifier, 0.1 g of attractant, 20 g of polyol, and the balance of water.

[0076] Embodiment 22

[0077] The composition of each 100 g of nanostructured lipid carrier is as follows:

[0078] Flurellana 10 g;

[0079] Oleic acid 12 g;

[0080] Glyceryl monostearate 8 g;

[0081] Tween 20 4.8 g;

[0082] Poloxamer 407 3.2 g;

[0083] Barbecue flavor 0.1 g;

[0084] Propylene glycol 20 g;

[0085] The balance is water for injection.

[0086] Embodiment 23

[0087] The composition of each 100 g of nanostructured lipid carrier is as follows:

[0088] Flurellana 1 g

[0089] Oleic acid 12 g

[0090] Stearic acid 8 g

[0091] Tween 80 4.8 g

[0092] Poloxamer 407 3.2 g

[0093] Chicken liver flavor 0.1 g

[0094] Polyethylene glycol 400 15 g

[0095] The balance is water for injection.

[0096] Embodiment 24

[0097] The composition of each 100 g of nanostructured lipid carrier is as follows:

[0098] Flurellana 8 g

[0099] Ethyl acetate 12 g

[0100] Glyceryl monostearate 8 g

[0101] Tween 20 4.8 g

[0102] Poloxamer 188 3.2 g

[0103] Barbecue flavor 0.1 g

[0104] Macrogol 200 20 g

[0105] The balance is water for injection.

[0106] Comparative Example 1

[0107] Flurellan chewable tablets (Bravetor)

[0108] Comparative Example 2

[0109] The composition of each 100 g of nanostructured lipid carrier is as follows:

[0110] Flurellana 10 g

[0111] Oleic acid 12 g

[0112] Glyceryl monostearate 8 g

[0113] Tween 20 4.8 g

[0114] Poloxamer 407 3.2 g

[0115] Beef flavor 0.1 g

[0116] The balance is water for injection.

[0117] Investigation Example 1

[0118] Quality inspection: appearance observation, fluidity after standing for 48 hours, particle size and Zeta potential, encapsulation efficiency. Comparative Example 2 has large particle size, low encapsulation efficiency, small absolute value of potential, and poor system stability.

[0119] The particle size, polymer dispersibility index (PDI) and Zeta potential of the FLM-NLCs samples prepared in Examples 22-24 and Comparative Example 2 were measured using a Malvern laser particle size analyzer (Zetasizer Nano ZS90, Malvern). The samples were diluted to the specified detection concentration range in advance, and about 1 mL of the dilution was taken into the sample pool and placed in the instrument for measurement; each sample was measured 3 times, and the detection angle was 90 ° , temperature 25 ℃, equilibration time before sampling is 120 s. After the sample test is completed, the sample pool needs to be cleaned before it can be used again.

[0120] The content and encapsulation efficiency of the FLM-NLCs sample were determined by centrifugation combined with UV-visible absorption spectroscopy. FLM-NLCs were accurately weighed, and purified water was added to make the volume to 100 mL. The volume was mixed to obtain the FLM-NLCs sample test solution. 0.1 mL of the FLM-NLCs sample test solution was taken and made up to 10 mL with acetonitrile. The solution was shaken upside down to mix, and ultrasonic demulsification was performed for 10 min to obtain the FLM-NLCs demulsified solution.

[0121] Encapsulation efficiency determination: 10 mL of FLM-NLCs sample solution was placed in a 10 mL centrifuge tube and centrifuged at 5000 rpm for 20 min. 0.1 mL of the supernatant was taken and made up to 10 mL with acetonitrile. After inversion and shaking to mix, the free drug amount (W) was calculated based on the obtained peak area.游离 ), and the FLM-NLCs demulsified solution was taken for UV-Vis analysis. The total amount of drug (W 总 );

[0122] The encapsulation efficiency was calculated as follows:

[0123]

[0124] Where W 总 is the total amount of flurella in FLM-NLCs, W 游离 is the amount of free flurellana in FLM-NLCs, and the test results are shown in Table 1;

[0125] Table 1

[0126]

[0127] Note: The particle size, PDI and Zeta potential in the table are all average values; the more “+”, the better the fluidity.

[0128] It can be seen from Table 1 that the FLM-NLCs prepared by the preparation method provided in the present application have a smaller particle size, a more uniform molecular weight distribution, a stable system, and a high encapsulation efficiency.

[0129] Investigation Example 2

[0130] Stability investigation: The FLM-NLCs samples were placed under freezing (-20±2℃), room temperature (25±2℃), and high temperature (60±2℃) conditions for 10 days and 30 days, respectively. After sampling, FLM-NLCs demulsifiers were prepared according to the sample processing method to detect the content of flurellana by UV spectrophotometry. The results are shown in Table 2;

[0131] Table 2

[0132]

[0133] It can be seen from Table 2 that the FLM-NLCs prepared by the preparation method provided in this application have good stability and stable product quality.

[0134] Investigation Example 3

[0135] In vitro release test: Dynamic membrane dialysis was used to determine the in vitro release of the flurana nanostructured lipid carrier samples; about 250 mg of the flurana sample (samples of Example 22 and Comparative Example 1-2, n=5) was added to a pre-treated dialysis bag and placed in a dissolution apparatus. Samples were taken at predetermined time points (0.25h, 0.5h, 1h, 1.5h, 2h, 4h), and after filtering with a 0.22 μm microporous membrane, the content was determined by UV-spectrophotometry. After each sampling, an equal amount of fresh buffer was added. The results are shown in Table 1. Figure 1 As shown, the FLM-NLCs prepared by the preparation method provided in the present application have a higher release rate.

[0136] Investigation Example 4

[0137] Pharmacokinetic study: 15 beagles weighing about 10 kg were randomly divided into 3 groups, each with 5 animals, namely the Example 22 administration group (250 mg), the Comparative Example 1 administration group (250 mg) and the Comparative Example 2 administration group (250 mg). The drugs were orally administered. The plasma of all animal blood samples was collected before and after administration at different times, and the content of flurellana in the plasma was detected. The results are as follows: Figure 2 As shown, in Example 22, Comparative Example 2 and Comparative Example 1, flurana was prepared into a nanostructured lipid carrier. At the same time, the drug concentration in plasma of the nanostructured lipid carrier dosage form was higher than that of the chewable tablet dosage form; in Example 22 and Comparative Example 2, polyols were introduced into the components, and the drug concentration in plasma was significantly increased, indicating that the addition of polyols can significantly improve the bioavailability of flurana.

[0138] Investigation Example 5

[0139] Clinical efficacy trial: 60 dogs infected with mites, fleas and ticks were collected and randomly divided into 3 groups, 20 in each group, the low-dose administration group of Example 22 (about 12.5 mg / kg), the high-dose administration group of Example 22 (about 25 mg / kg), and the administration group of Comparative Example 1 (about 25 mg / kg). The study period was 12 weeks after administration, and the efficacy was determined by observing the clinical symptoms and parasite separation of the sick dogs before and after medication.

[0140] According to the clinical symptoms, the scores can be 0, 1, 2, 3, or 4. The scores of each animal are recorded to obtain the specific symptom score (SCS), which ranges from 0 to 4. The skin lesion scoring table is shown in Table 3;

[0141] Table 3 Skin lesion scoring table

[0142]

[0143] Note: "Local" means that the parasite occurs in 1-2 parts of the dog, such as the auricle, shoulder blade, waist and back, lower abdomen, buttocks, legs and tail root. If the parasite occurs in three or more parts, it is recorded as "multiple". If the distribution parts are not specific or the boundaries are unclear, it is also recorded as multiple.

[0144] Experimental results:

[0145] (1) Effectiveness: In SD84, the average reduction rate of the number of parasites in the experimental dogs was ≥90%, and there was no itching, rash, dandruff or self-biting injury in the affected area; the clinical specific symptom score (SCS) of 1-2 was ≤1, and the SCS of 3-4 was 0, which was considered effective. The effective rate was calculated based on this, and the effective rate = the number of effective animals / the total number of animals in the group. The results are shown in Table 4;

[0146] (2) Cure rate: In SD84, the number of parasites in the experimental dogs was 0, there was no itching, no rash, no dandruff in the affected area, or no self-biting lesions in the experimental dogs, and the clinical specific symptom score (SCS) was 0, which was considered cured. The cure rate was calculated based on the number of cured animals, cure rate = number of cured animals / total number of animals in the group. The results are shown in Table 4.

[0147] (3) Parasite isolation rate: Parasite isolation and counting were performed at SD28, SD56, and SD84 after administration. If parasites were isolated at any time, the animal was judged to have isolated parasites. Parasite isolation rate = number of animals with isolated parasites / total number of animals in the group. The results are shown in Table 4.

[0148] Table 4

[0149]

[0150] It can be seen from Table 4 that the flurellana nanostructured lipid carrier prepared by the preparation method provided in the present application is highly effective against parasites at a low dose and has a high cure rate, and has significant clinical application value.

[0151] The present application provides a method for preparing a flurellan nanostructured lipid carrier, which specifically comprises the following steps: oil phase preparation: heating and melting a main emulsifier, lipids and flurellan in a water bath to obtain an oil phase reserve liquid; water phase preparation: swelling and mixing an attractant, an auxiliary emulsifier, a polyol and water in a water bath to obtain an water phase reserve liquid; colostrum preparation: adding the oil phase reserve liquid to the water phase reserve liquid, shearing it with a high shear instrument to form a primary mixed liquid, and homogenizing and circulating the primary mixed liquid to obtain colostrum; cooling the colostrum to obtain a flurellan nanostructured lipid carrier; and providing a flurellan nanostructured lipid carrier semisolid cream. The cream can be administered orally or externally for the prevention and treatment of external parasitic diseases of pets such as dogs and cats; the application not only improves the performance of the nanostructured lipid carrier by adding a quantitative polyol and lipid compound in the aqueous phase, making the main drug in the nanostructured lipid carrier more evenly distributed, the system more stable, and the encapsulation rate high, but also improves the release and absorption of the main drug in the nanostructured lipid carrier, solves the solubility of flurellana, and improves the oral bioavailability, promotes the drug to better exert its therapeutic effect in the body, enables pets to improve the therapeutic effect while reducing the dosage of medication, improves the safety of the drug, reduces damage to pets, and has significant clinical application value.

[0152] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of this application, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0153] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application should be included in the protection scope of the present application.

Claims

1. A method for preparing a fluorouracil nanostructured lipid carrier, characterized in that: The specific steps include: (i) Preparation of oil phase: melt the main emulsifier, lipid and flurellanine in a water bath to prepare the oil phase standby solution; (ii) Preparation of aqueous phase: swell and mix the attractant, emulsifier, polyol and water in a water bath to obtain an aqueous phase standby solution; (III) Preparation of colostrum: adding the oil phase reserve solution to the water phase reserve solution, shearing to form a primary mixed solution, homogenizing and circulating the primary mixed solution to obtain colostrum; cooling the colostrum to obtain a flurella nanostructured lipid carrier; The lipids in step (i) include liquid lipids and solid lipids, and the mass ratio of the liquid lipids to the solid lipids is 5-7:3-5; The liquid lipid is one of oleic acid, ethyl acetate, epoxidized soybean oil, isopropyl myristate, triolein or castor oil; the solid lipid is one of distearin, palmitic acid, stearic acid, lauric acid, behenic acid or monostearin; The primary emulsifier in step (i) is Tween 20 or Tween 80; the auxiliary emulsifier in step (ii) is poloxamer 188 or poloxamer 407; the mass ratio of the primary emulsifier to the auxiliary emulsifier is 1-1.5: 1-1.5; The components of the flurella nanostructured lipid carrier are as follows: every 100 g of the flurella nanostructured lipid carrier contains 0.1-10 g of flurella, 20 g of lipid, 8 g of emulsifier, 0.1 g of attractant, 20 g of polyol, and the balance is water.

2. The method for preparing a fluorouracil nanostructured lipid carrier according to claim 1, characterized in that: The temperature of the water bath in step (i) and step (ii) is 50-80°C.

3. The method for preparing a fluorouracil nanostructured lipid carrier according to claim 1, characterized in that: The polyol in step (ii) is one of propylene glycol, glycerol, polyethylene glycol 200 or polyethylene glycol 400.

4. The method for preparing a fluororana nanostructured lipid carrier according to claim 1, characterized in that: The appetite attractant in step (ii) is one of barbecue flavor, chicken liver flavor or beef flavor, and the colostrum in step (iii) is cooled to room temperature.

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