Nano preparation for treating migraine and preparation method and application thereof

Abstract

The invention provides a nano preparation for treating migraine as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The nano preparation provided by the invention takes beta-cyclodextrin as a capsule material, and takes an active component and vegetable oil as core materials; the active ingredients comprise the following components: a rice bran extract, vitamin C, a radix angelicae extract and gamma-aminobutyric acid; wherein the rice bran extract can resist inflammation and block calcitonin gene related peptides or receptors thereof; the radix angelicae dahuricae extract can improve the content of an inflammatory medium serotonin; the vitamin C can relieve brain blood vessels; the gamma-aminobutyric acid can regulate brain nerves and promote brain metabolism. The nano preparation disclosed by the invention can improve migraine from multiple angles. The beta-cyclodextrin inclusion compound is prepared by taking beta-cyclodextrin as a capsule material and taking the active component and the vegetable oil as core materials, so that the active component can be slowly released, the effects of sustained release and continuous effect of the active component within a period of time can be achieved, and long-acting treatment of migraine can be realized.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and in particular relates to a nano preparation for treating migraine, and a preparation method and application thereof. Background Art

[0002] Approximately 15% of the world's population is affected by migraine. Migraine is characterized by recurrent attacks of moderate to severe headaches. Typically, the headaches involve one half of the head, are throbbing in nature, and last for 2 to 72 hours. Symptoms of migraine include nausea, vomiting, and sensitivity to light, sound, or smells. The pain is often worsened by physical exercise. Conventional treatments for migraine include simple analgesics for the headache, such as ibuprofen or paracetamol (acetaminophen), and other medications for nausea and avoidance of triggers. However, frequent use of medications may lead to medication overuse headaches, in which headaches become more severe and more frequent, and for this reason, there is a continued need to develop new drugs to treat migraine. Summary of the invention

[0003] The purpose of the present invention is to provide a nano preparation for treating migraine and a preparation method and application thereof. The nano preparation of the present invention can effectively treat migraine and provides a new solution for the treatment of migraine.

[0004] The invention provides a nano preparation for treating migraine, which uses beta-cyclodextrin as a capsule material and uses active ingredients and vegetable oil as core materials; the active ingredients include the following components in parts by weight: 2 to 6 parts of rice bran extract, 0.3 to 0.5 parts of vitamin C, 0.2 to 0.4 parts of angelica dahurica extract and 0.1 to 0.4 parts of gamma-aminobutyric acid; the ratio of the mass of the rice bran extract to the volume of the vegetable oil is 0.1 to 1 g / 1 mL.

[0005] Preferably, the mass ratio of the β-cyclodextrin to the active ingredient is (1-30):1.

[0006] Preferably, the particle size of the nano preparation is ≤500 nm.

[0007] Preferably, the vegetable oil comprises corn oil.

[0008] The present invention also provides a method for preparing the nano preparation described in the above scheme, comprising the following steps: first mixing the rice bran extract and the vegetable oil to obtain a mixed liquid; second mixing the vitamin C, the angelica extract and the γ-aminobutyric acid to obtain a mixed material; third mixing the mixed liquid, the mixed material and a saturated aqueous solution of β-cyclodextrin, and performing high-pressure homogenization to obtain an inclusion compound; and sequentially filtering, washing and drying the inclusion compound to obtain the nano preparation.

[0009] Preferably, the pressure of the high-pressure homogenization is 25 to 35 MPa; the temperature of the high-pressure homogenization is 20 to 30° C.; the number of high-pressure homogenization is 4 to 6 times, and the time of each high-pressure homogenization is 10 to 15 minutes.

[0010] Preferably, after the high-pressure homogenization, the material after the high-pressure homogenization is subjected to ultrasound; the temperature of the ultrasound is 20 to 30° C.; the time of the ultrasound is 60 to 120 minutes; the power of the ultrasound is 400 to 800 W; and the frequency of the ultrasound is 1 to 10 KHz.

[0011] The present invention also provides the use of the nano preparation described in the above scheme or the nano preparation prepared by the preparation method in preparing a drug for treating migraine.

[0012] The present invention also provides a drug for treating migraine, the drug comprising an active ingredient and a pharmaceutically acceptable excipient; the active ingredient comprises the nano preparation described in the above scheme or the nano preparation prepared by the preparation method.

[0013] Preferably, the dosage form of the drug includes an oral preparation.

[0014] The present invention provides a nano preparation for treating migraine, which uses β-cyclodextrin as a capsule material, and uses active ingredients and vegetable oil as core materials; the active ingredients include the following components: rice bran extract, vitamin C, angelica dahurica extract and γ-aminobutyric acid. In the present invention, the main active ingredient of the rice bran extract is ferulic acid, and the rice bran extract has the function of anti-inflammation and blocking calcitonin gene-related peptide (CGRP) or its receptor; the main active ingredient of the angelica dahurica extract is komaric acid, and the angelica dahurica extract has the function of increasing the content of inflammatory mediator 5-hydroxytryptamine (5-HT); the vitamin C has the function of relaxing brain blood vessels; the γ-aminobutyric acid has the function of regulating brain nerves and promoting brain metabolism. The present invention combines rice bran extract, vitamin C, angelica dahurica extract and γ-aminobutyric acid, which can improve migraine from multiple angles. In addition, the present invention uses β-cyclodextrin as a capsule material, and uses active ingredients and vegetable oil as core materials to prepare a β-cyclodextrin inclusion compound, which can slowly release the active ingredient, achieve the effect of continuous release and continuous action of the active ingredient over a period of time, and can achieve long-term treatment of migraine. DETAILED DESCRIPTION

[0015] The invention provides a nano preparation for treating migraine, which uses beta-cyclodextrin as a capsule material and uses active ingredients and vegetable oil as core materials; the active ingredients include the following components in parts by weight: 2 to 6 parts of rice bran extract, 0.3 to 0.5 parts of vitamin C, 0.2 to 0.4 parts of angelica dahurica extract and 0.1 to 0.4 parts of gamma-aminobutyric acid; the ratio of the mass of the rice bran extract to the volume of the vegetable oil is 0.1 to 1 g / 1 mL.

[0016] In the present invention, the active ingredient is preferably composed of the following components in parts by mass: 2 to 6 parts of rice bran extract, 0.3 to 0.5 parts of vitamin C, 0.2 to 0.4 parts of angelica dahurica extract and 0.1 to 0.4 parts of γ-aminobutyric acid.

[0017] In the present invention, the active ingredient comprises 2 to 6 parts of rice bran extract, preferably 3 to 5 parts, and more preferably 4 parts by mass. In the present invention, the rice bran extract has the effects of anti-inflammation and blocking CGRP or its receptor. In the present invention, the main active ingredient of the rice bran extract is ferulic acid, and the mass content of ferulic acid in the rice bran extract is preferably ≥98%; in the present invention, the rice bran extract is preferably derived from conventional commercial products or prepared by the following method: defatted rice bran and natural deep eutectic solvent (NADES) are mixed, ultrasonic extraction is performed to obtain an ultrasonic extract, and the ultrasonic extract is sequentially concentrated and freeze-dried to obtain a rice bran extract; the NADES consists of β-cyclodextrin, choline chloride and D-glucose; the volume concentration of β-cyclodextrin in the NADES is 50%; the mass ratio of choline chloride to D-glucose is 1:1; the ratio of the mass of the defatted rice bran to the volume of NADES is 1g:20mL; the power of the ultrasonic extraction is 50W; the temperature of the ultrasonic extraction is 50°C; the duty cycle of the ultrasonic extraction is 50%; and the time of the ultrasonic extraction is 16min.

[0018] In the present invention, the active ingredient includes 0.3 to 0.5 parts of vitamin C, preferably 0.4 parts, by mass; the vitamin C has the function of relaxing cerebral blood vessels. In the present invention, the vitamin C is from conventional commercial sources.

[0019] In the present invention, the active ingredient includes 0.2-0.4 parts of Angelica dahurica extract, preferably 0.3 parts, by mass; the main active ingredient of the Angelica dahurica extract is komaric acid, and the Angelica dahurica extract functions to increase the content of the inflammatory mediator 5-hydroxytryptamine (5-HT). In the present invention, the preparation method of the Angelica dahurica extract preferably includes the following steps: mixing Angelica dahurica powder and methanol, extracting to obtain an extract, and successively performing reduced pressure concentration and freeze drying on the extract to obtain the Angelica dahurica extract; the extraction temperature is 60°C; the extraction time is 36h; the ratio of the mass of the Angelica dahurica powder to the volume of methanol is preferably 1g: (6-10)mL, more preferably 1g: 8mL.

[0020] In the present invention, the active ingredient includes 0.1 to 0.4 parts by mass, preferably 0.2 to 0.3 parts of γ-aminobutyric acid; the γ-aminobutyric acid regulates brain nerves and promotes brain metabolism. In the present invention, the γ-aminobutyric acid is derived from conventional commercial sources.

[0021] In the present invention, the active ingredient is preferably pulverized by a nano-scale ultrafine pulverizer before use; the particle size of the active ingredient is preferably ≤50nm, more preferably 2-25nm.

[0022] In the present invention, the mass ratio of the β-cyclodextrin to the active ingredient is preferably (1-30):1, more preferably (1-10):1, and most preferably (2-5):1.

[0023] In the present invention, the particle size of the nano preparation is preferably ≤500 nm, more preferably ≤200 nm, and most preferably ≤100 nm.

[0024] In the present invention, the vegetable oil preferably includes corn oil.

[0025] The present invention also provides a method for preparing the nanoformulation described in the above scheme, comprising the following steps:

[0026] The rice bran extract and the vegetable oil are first mixed to obtain a mixed solution;

[0027] The vitamin C, the angelica dahurica extract and the gamma-aminobutyric acid are mixed for the second time to obtain a mixture;

[0028] The mixed solution, the mixed material and the saturated aqueous solution of β-cyclodextrin are mixed for the third time, and high pressure homogenized to obtain an inclusion compound;

[0029] The inclusion compound is filtered, washed and dried in sequence to obtain a nano preparation.

[0030] The present invention first mixes the rice bran extract and the vegetable oil to obtain a mixed solution.

[0031] In the present invention, the first mixing is preferably stirring mixing; the present invention has no special restrictions on the temperature and time of the first mixing, as long as the mixing is uniform.

[0032] The present invention secondly mixes the vitamin C, the angelica root extract and the gamma-aminobutyric acid to obtain a mixture.

[0033] The present invention has no special limitation on the second mixing, as long as the mixing is uniform.

[0034] After obtaining the mixed liquid and the mixed material, the present invention thirdly mixes the mixed liquid, the mixed material and a saturated aqueous solution of beta-cyclodextrin, and performs high-pressure homogenization to obtain an inclusion compound.

[0035] In the present invention, the third mixing is preferably stirring mixing. In the present invention, the saturated aqueous solution of β-cyclodextrin is preferably prepared by the following method: at 60° C., a saturated solution of β-cyclodextrin with a mass fraction of 15% is prepared by using distilled water.

[0036] In the present invention, the pressure of the high-pressure homogenization is preferably 25-35 MPa, more preferably 30 MPa; the temperature of the high-pressure homogenization is preferably 20-30°C, more preferably 25°C; the number of high-pressure homogenization is preferably 4-6 times, and the time of each high-pressure homogenization is preferably 10-15 minutes. In the present invention, the inclusion can be promoted, the inclusion rate can be increased, and the particle size of the inclusion compound can be reduced by homogenization treatment of high-pressure homogenization.

[0037] After the high-pressure homogenization, the present invention preferably further comprises ultrasonicating the material after the high-pressure homogenization; the temperature of the ultrasonication is preferably 20-30°C, more preferably 25°C; the time of the ultrasonication is preferably 60-120min, more preferably 80-100min; the power of the ultrasonication is preferably 400-800W, more preferably 500-600W; the frequency of the ultrasonication is preferably 1-10KHz.

[0038] After obtaining the inclusion compound, the present invention sequentially performs suction filtration, washing and drying on the inclusion compound to obtain the nano preparation.

[0039] In the present invention, the reagent used for washing includes water. In the present invention, the drying includes freeze drying.

[0040] The present invention also provides the use of the nano preparation described in the above scheme or the nano preparation prepared by the preparation method in preparing a drug for treating migraine.

[0041] The present invention also provides a drug for treating migraine, the drug comprising an active ingredient and a pharmaceutically acceptable excipient; the active ingredient comprises the nano preparation described in the above scheme or the nano preparation prepared by the preparation method.

[0042] In the present invention, the migraine preferably includes vestibular migraine, retinal migraine, chronic migraine or paroxysmal migraine, preferably chronic migraine.

[0043] In the present invention, the dosage form of the drug preferably includes an oral preparation.

[0044] In the present invention, the pharmaceutically acceptable excipient is any known compound or combination of known compounds known to those skilled in the art that can be used to prepare a pharmaceutical composition. In the specific implementation of the present invention, the pharmaceutically acceptable excipient preferably includes citric acid.

[0045] The present invention also provides a method for treating migraine, comprising the following steps: administering a therapeutically effective amount of the nanoformulation or drug described in the above scheme to the subject; the therapeutically effective amount is any amount of the drug dose required to produce the desired effect when administered to the subject.

[0046] In order to further illustrate the present invention, a nano preparation for treating migraine provided by the present invention, a preparation method thereof and an application thereof are described in detail below in conjunction with examples, but they should not be construed as limiting the scope of protection of the present invention.

[0047] The mass content of ferulic acid in the rice bran extract in the embodiment of the present invention is 98%, which is food grade and purchased from Shaanxi Snot Biotechnology Co., Ltd. The Angelica dahurica extract in the embodiment of the present invention is prepared by the following preparation method: 20g of Angelica dahurica powder and 16mL of methanol are mixed, extracted at 60°C for 36h to obtain an extract, and the extract is pressurized and concentrated in turn with a concentration ratio of 5:1, and freeze-dried at -50°C for 6h to obtain the Angelica dahurica extract. Vitamin C in the embodiment of the present invention is food grade and purchased from Xi'an Musen Bioengineering Co., Ltd. γ-aminobutyric acid in the embodiment of the present invention is food grade and purchased from Jiangsu Caiwei Biotechnology Co., Ltd.

[0048] The above components are pulverized by a nano-scale ultra-fine pulverizer before use, and the particle size is 5 to 25 nm.

[0049] The subjects of the clinical examples of the present invention met the diagnostic criteria of "Classification and Diagnosis of Headache Disorders" (Guidelines), and the subjects were informed and voluntarily signed the informed consent.

[0050] Example 1

[0051] 1. Formula: active ingredient, β-cyclodextrin and corn oil; wherein, β-cyclodextrin 500g, corn oil 200mL; the active ingredient is composed of the following components: rice bran extract 200g, vitamin C 30g, angelica dahurica extract 20g and γ-aminobutyric acid 10g.

[0052] 2. Preparation method:

[0053] 1) stirring and mixing the rice bran extract and the vegetable oil to obtain a mixed solution;

[0054] 2) mixing the vitamin C, the angelica dahurica extract and γ-aminobutyric acid to obtain a mixture;

[0055] 3) At 60° C., a saturated solution of β-cyclodextrin with a mass fraction of 15% was prepared using distilled water;

[0056] 4) After the mixed solution, the mixed material and the saturated aqueous solution of β-cyclodextrin are stirred and mixed uniformly, high pressure homogenization is performed under the conditions of a homogenization pressure of 30 MPa, 5 homogenization times, each time for 10 min, and a temperature of 25° C. to obtain an inclusion compound;

[0057] 5) The inclusion compound is filtered, washed with water and freeze-dried in sequence to obtain a nano preparation.

[0058] The nanoparticles were tested by Malvern particle size analyzer, and the diameter distribution of the nanoparticles was 116.89-453.63 nm, and the inclusion rate was 72.84%.

[0059] Example 2

[0060] After high pressure homogenization in step 4) of Example 1, the high pressure homogenized material was subjected to ultrasound, and the ultrasound conditions were: ultrasound temperature 25° C., time 90 min and power 800 W. The rest was the same as Example 1.

[0061] The diameter of the nanoparticles was measured by Malvern particle size analyzer and the distribution was 51.63-262.78 nm. The inclusion rate was 83.39%.

[0062] Example 3

[0063] 1. Formula: active ingredient, β-cyclodextrin and corn oil; wherein, β-cyclodextrin 200g, corn oil 60mL; the active ingredient is composed of the following components: rice bran extract 30g, vitamin C 5g, angelica dahurica extract 4g and γ-aminobutyric acid 4g.

[0064] 2. The preparation method is the same as that in Example 1.

[0065] The particle size of the nanoparticles was measured by a particle size analyzer, and the results showed that the particle size of the nanoparticles ranged from 183.24 to 477.51 nm, and the inclusion rate was 75.76%.

[0066] Test Example 1

[0067] In order to evaluate the effect of the nanoformulation prepared in Example 1 on treating migraine, a chronic migraine mouse model was constructed, and the experimental process was as follows:

[0068] 1) Modeling of 36 SPF SD male rats, 10-12 weeks old, with a body weight of 200-250g. After 7 days of adaptive feeding, the rats were randomly divided into a blank group, a model group, a low-dose nanoformulation group, a medium-dose nanoformulation group, a high-dose nanoformulation group, and a positive control group, with 6 rats in each group. On the morning of the 1st, 3rd, 5th, 7th, and 9th days, rats in the model group, the low-dose nanoformulation group, the medium-dose nanoformulation group, the high-dose nanoformulation group, and the positive control group were subcutaneously injected with 10 mg / kg of nitroglycerin. Rats in the blank group were injected with the same volume of physiological salt β-cyclodextrin. After 9 days, the rats were anesthetized with 40 mg / kg sodium pentobarbital solution, decapitated, the fur was cut to expose the skull, and the skull was pried open with hemostatic forceps to fully expose the brain tissue. Curved forceps were used to carefully slide along the outer edge of the brain and the bottom of the brain to remove excess tissue and nerves. The brain was bluntly dissected and the trigeminal ganglion (the anterior trigeminal nerve pressure mark at the tip of the petrous part of the middle cranial fossa) was obtained. The whole process of sampling was carried out on an ice box, and the samples were placed in 2 mL cryovials for temporary liquid nitrogen low-temperature storage, and then placed in a -80°C refrigerator.

[0069] For 7 consecutive days starting from the beginning of modeling, the oral dose of the low-dose group of the nanoformulation was 3 mg / kg, the medium-dose group of the nanoformulation was 6 mg / kg per day, the medium-dose group of the nanoformulation was 12 mg / kg per day, the positive control group was gavaged with 0.9 mg / kg of sibelium, and the blank group and the model group were gavaged with an equal volume of ultrapure β-cyclodextrin every day.

[0070] 2) Rats Pain Surface Capacity Scale Scoring

[0071] All rats were placed in a plexiglass box (30 cm × 30 cm × 25 cm) 40 minutes after the injection of nitroglycerin on the 9th day. The plastic dome was covered with a mesh metal floor, allowing the animals to walk freely but not jump. After 20 minutes of adaptation, their facial expressions were recorded using photography and video equipment and scored according to the Rat Pain Scale (RGS). The scoring criteria were based on changes in facial expression, which mainly included: ① tightening of the eye sockets; ② changes in the position of the ears; ③ swelling of the face; and ④ swelling of the root of the nose. The scores ranged from 0 to 2 from mild to severe, with 0 being absent, 1 being moderate, and 2 being the most obvious.

[0072] Before modeling, the exploratory behavior and movement of the rats were not significantly different from normal. After modeling, the body temperature and weight did not change significantly, but there were phenomena of reduced food intake, increased head scratching, reduced exploratory behavior, and painful facial expressions (including tight eye sockets, changes in ear position, and swelling of the face and nose root), indicating that the migraine model was successfully established.

[0073] The pain facial scores of rats in each group are shown in Table 1. The results showed that compared with the blank group, the pain facial score of the model group was significantly increased (P < 0.05); compared with the model group, the pain facial scores of rats in the nanopreparation medium dose group, nanopreparation high dose group, and positive control group were significantly decreased (P < 0.05), see Table 1.

[0074] Table 1 Painful facial expression score table of rats in each group

[0075]

[0076] 3) Determination of biochemical indicators (NO, DA, CGRP, 5-HT) in rats

[0077] After the rat pain surface capacity scale score measurement was completed, blood was collected from the orbital vein of the rats in each group, and the serum was separated. The NO content in the serum was measured by the nitrate reductase method, and the DA (dopamine), CGRP, and 5-HT contents in the serum were measured by the ELISA method. The measurement results are shown in Table 2.

[0078] Table 2 Results of biochemical index determination in rats

[0079]

[0080]

[0081] As can be seen from Table 2, after modeling, the average β-cyclodextrin levels of NO, CGPR, DA and 5-HT in the serum of rats were significantly increased. After administration of the nanoformulation of Example 1 and Sibelium, the above four biochemical indicators were significantly decreased. It can be seen that Sibelium of the present invention regulates the β-cyclodextrin levels of vasoactive substances and their neurotransmitters related to pain, thereby reducing neuroinflammation and achieving the effect of effectively treating migraine.

[0082] Clinical Case 1

[0083] The nanoformulation prepared in Example 1 is applied to migraine without aura

[0084] Patient's condition: Male, 39 years old, employee;

[0085] Symptoms: migraine attacks without aura, accompanied by dizziness or nausea when changing body position, each attack lasting several minutes or half an hour, with a frequency of at least 4 to 5 times a week, sometimes almost every day, poor sleep quality, difficulty falling asleep after waking up, irritability, and attacks for at least one year;

[0086] Treatment: Orally take the nanoformulation prepared in Example 1 with warm water, 30 g per day, 10 g in the morning, 10 g at noon, and 10 g in the evening, for one week.

[0087] Improvement after treatment: After treatment, the frequency of migraine attacks decreased from at least 4 to 5 times per week to 4 to 6 times per month, the symptoms of dizziness were alleviated, nausea basically disappeared, sleep quality improved, and the condition was significantly relieved.

[0088] Clinical Case 2

[0089] Example 2: Nanoformulation prepared for chronic migraine

[0090] Patient's condition: Female, 58 years old, retired.

[0091] Symptoms: Each migraine attack lasts 1 to 2 hours. The current frequency is about 15 times a month. It has occurred for several years and the frequency has gradually increased. There is poor appetite and weight loss.

[0092] Treatment: Oral administration of the nanoformulation prepared in Example 2, the dosage is warm water, 25g per day, 10g in the morning, 10g at noon, 5g at night, for 2 weeks; after 2 weeks, the dosage of the nanoformulation is adjusted to 30g per day, 10g in the morning, 10g at noon, 10g at night, and taken for another 2 weeks.

[0093] Improvement after treatment: There was no migraine attack within 1 week after stopping the medication, but it recurred 1 week later. The patient had 1 to 3 attacks per month, which were relieved by taking painkillers. Consider continuing treatment.

[0094] Clinical Case 3

[0095] Example 3: Nanoformulation prepared for paroxysmal migraine

[0096] Patient's condition: male, 21 years old, student.

[0097] Symptoms: Each migraine attack lasts for a few seconds or minutes, the attacks are irregular, and there is vomiting during the attack, which can be relieved after rest.

[0098] Treatment: Orally take the nanoformulation prepared in Example 3 with warm water, 30 g per day, 10 g in the morning, 10 g at noon, and 10 g in the evening, for 5 days.

[0099] Improvement after treatment: No migraine attacks occurred during the medication period and the quality of life was significantly improved.

[0100] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A nano preparation for treating migraine, characterized in that: β-cyclodextrin is used as the capsule material, and active ingredients and vegetable oil are used as the core material; The active ingredients include the following components in parts by weight: 2 to 6 parts of rice bran extract, 0.3 to 0.5 parts of vitamin C, 0.2 to 0.4 parts of angelica dahurica extract and 0.1 to 0.4 parts of gamma-aminobutyric acid; The ratio of the mass of the rice bran extract to the volume of the vegetable oil is 0.1-1 g / 1 mL.

2. The nanoformulation according to claim 1, characterized in that The mass ratio of the β-cyclodextrin to the active ingredient is (1-30):

1.

3. The nanoformulation according to claim 1, characterized in that The particle size of the nano preparation is ≤500nm.

4. The nanoformulation according to claim 1 or 3, characterized in that: The vegetable oil includes corn oil.

5. The method for preparing the nanoformulation according to any one of claims 1 to 4, characterized in that: The following steps are involved: The rice bran extract and the vegetable oil are first mixed to obtain a mixed solution; The vitamin C, the angelica dahurica extract and the gamma-aminobutyric acid are mixed for the second time to obtain a mixture; The mixed solution, the mixed material and the saturated aqueous solution of β-cyclodextrin are mixed for the third time, and high pressure homogenized to obtain an inclusion compound; The inclusion compound is filtered, washed and dried in sequence to obtain a nano preparation.

6. The preparation method according to claim 5, characterized in that: The pressure of the high-pressure homogenization is 25-35 MPa; the temperature of the high-pressure homogenization is 20-30° C.; the number of high-pressure homogenization is 4-6 times, and the time of each high-pressure homogenization is 10-15 minutes.

7. The preparation method according to claim 5 or 6, characterized in that: After the high-pressure homogenization, the material after the high-pressure homogenization is ultrasonically processed; the temperature of the ultrasonic process is 20 to 30° C.; the time of the ultrasonic process is 60 to 120 minutes; the power of the ultrasonic process is 400 to 800 W; and the frequency of the ultrasonic process is 1 to 10 KHz.

8. Use of the nanoformulation according to any one of claims 1 to 4 or the nanoformulation prepared by the preparation method according to any one of claims 5 to 7 in the preparation of a drug for treating migraine.

9. A drug for treating migraine, characterized in that: The drug comprises an active ingredient and a pharmaceutically acceptable excipient; the active ingredient comprises the nanoformulation described in any one of claims 1 to 4 or the nanoformulation prepared by the preparation method described in any one of claims 5 to 7.

10. The drug according to claim 9, characterized in that The dosage form of the drug includes oral preparations.

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