WO2023077715A1 - Nanoemulsion preparation for treating migraines, and preparation method therefor and use thereof - Google Patents

Abstract

A method for preparing a nanoemulsion preparation for treating migraines comprises the following steps: selecting Angelicae sinensis radix and Chuanxiong rhizoma as raw materials, and extracting volatile oil by means of a supercritical extraction method, wherein the weight ratio of Angelicae sinensis radix to Chuanxiong rhizoma is 1:0.5-2; and selecting chitosan and alginate, loading the volatile oil on same by means of a single-emulsion solvent evaporation method to complete the preparation of a nanoemulsion, wherein the particle size of the nanoemulsion preparation is 200-300 nm. Further disclosed are a nanoemulsion preparation prepared by the above method and used for treating migraines, and the use of the nanoemulsion preparation prepared by the above method and used for treating migraines in the preparation of a food rproduct or a drug for treating migraines.

Description

A nanoemulsion preparation for treating migraine and its preparation method and application

Cross References to Related Applications

This disclosure claims the priority of the Chinese patent application with the application number "CN 202111285758.0" and the title "A nanoemulsion preparation for treating migraine and its preparation method and application" submitted to the China Patent Office on November 02, 2021. The entire contents are incorporated by reference in this disclosure.

technical field

The disclosure relates to the technical field of traditional Chinese medicine extracts and preparation, in particular, to a nanoemulsion preparation for treating migraine and its preparation method and application.

Background technique

Migraine (Migraine) is a common episodic neurovascular dysfunction, its symptoms are usually pulsating severe headache in unilateral or bilateral sites, accompanied by a variety of accompanying neurological symptoms, including nausea, vomiting, Photophobia and fear. Epidemiological studies have shown that the global incidence of migraine is about 43% for women and 18% for men. Moreover, this chronic disease with high morbidity and low recovery rate severely reduces the quality of life of patients, further causing significant economic losses.

The bergamot formula is famous and widely used as a traditional Chinese medicine for migraine and dysmenorrhea. It was first recorded in the famous formula book "Pu Ji Ben Shi Fang" in the Song Dynasty. According to the theory of traditional Chinese herbal medicine, it is believed that the onset of headaches is usually caused by wind-cold, blood stasis and nutritional deficiencies. This classic prescription is composed of two traditional Chinese medicines, Angelica sinensis (Oliv.) Diels) and Chuanxiong (Ligusticum chuanxiong Hort.), in a mass ratio of 2:1. Pharmacological studies have shown that Chuanxiong has warm and spicy properties, which can improve Qi and blood circulation, dispel wind and relieve pain, especially for headaches and rheumatoid arthritis. Another herb, Angelica, is widely used as a main treatment for blood tonification and dysmenorrhea.

At present, the cause of migraine is still unclear. Although there are some traditional Chinese and Western medicine treatments that can relieve the symptoms, long-term medication is usually required, but the curative effect is not ideal, and migraine cannot be cured well. Once the medicine is stopped, the headache symptoms tend to recur, and There are different degrees of side effects, such as the impact on liver and kidney functions, which bring greater pain to patients and cost more.

Many Chinese herbal compounds have been shown to have good analgesic, anti-inflammatory and vasomodulatory activities, thus having an important and direct impact on migraine. Studies have shown that the effect of bergamot powder on migraine is related to the regulation of inflammatory cytokines, intestinal flora and neurovascular system, as well as the transmission of pain signals. In addition, since the active part of bergamot powder is a fat-soluble component, a drug delivery system based on polysaccharides was developed to ensure its pharmacological effects. As a drug carrier, polysaccharide has good biocompatibility and controlled release effect. Bergamot volatile oil has many advantages in the treatment of migraine, such as safety, definite effect and less adverse reactions. Bergamot volatile oil can relieve migraine by regulating the level of vasoactive substances, interfering with pain signal transduction pathways, regulating the secretion of inflammatory cytokines and the abundance of intestinal flora, and maintaining normal blood flow in the brain, and can also be combined with other drugs Comprehensive treatment. Angelica and Chuanxiong are commonly used herbal medicines, which have significant curative effects in the treatment of pain diseases. At the same time, Angelica and Chuanxiong belong to Umbelliferae plants and are rich in phthalide compounds, but their physical and chemical properties, biological activities, especially their role in migraine are lack of in-depth research.

Contents of the invention

The present disclosure provides a nanoemulsion preparation for treating migraine, which uses the volatile oil of Angelica sinensis and Rhizoma Chuanxiong as active pharmaceutical ingredients, and is composed of acceptable auxiliary ingredients in the medicine. The effective pharmaceutical ingredients come from Angelica sinensis and Rhizoma Chuanxiong in a weight ratio of 1: 0.5-2 obtained by supercritical extraction.

In some embodiments, the volatile oil of Angelica sinensis and the volatile oil of Chuanxiong Rhizoma are used as active pharmaceutical ingredients, polysaccharide biomacromolecules are used as encapsulating materials, and the mixed oil of Angelica sinensis volatile oil and Ligusticum chuanxiong volatile oil is encapsulated in the presence of surfactants to produce Nanoemulsions.

In some embodiments, the active pharmaceutical ingredients are obtained by extracting and separating the volatile oil of Angelica Sinensis and Rhizoma Chuanxiong by means of supercritical carbon dioxide circulation and countercurrent.

In some embodiments, during the countercurrent extraction of volatile oil with supercritical carbon dioxide circulation, the two crude drug raw materials of Angelica sinensis and Rhizoma Chuanxiong are mixed and extracted simultaneously.

In some embodiments, the polysaccharide biomacromolecule is selected from alginate and chitosan.

In some embodiments, the surfactant is selected from Tween-80 (Tween-80), polyethylene glycol octyl phenyl ether-100 (TritonX-100) and sucrose fatty acid ester fatty amide (Ninol ) at least one of.

In some embodiments, the nanoemulsion formulation has a particle size of 150-300 nm.

In some embodiments, the particle size of the nanoemulsion formulation is 200-300 nm, such as 180-220 nm.

In some embodiments, the potential of the nanoemulsion formulation is 30-60 mV.

In some embodiments, the polymer dispersion index of the nanoemulsion formulation is 0.1-0.2.

The present disclosure also provides a method for preparing the above-mentioned nanoemulsion preparation for treating migraine, which includes: using angelica volatile oil and chuanxiong volatile oil as effective pharmaceutical ingredients, and preparing the nanoemulsion preparation by single emulsification solvent evaporation method.

In some embodiments, the mixed oil of angelica volatile oil and chuanxiong volatile oil is mixed with ethanol as the oil phase, and alginate is mixed with water and surfactant as the water phase, and the above oil phase is added to the water phase under stirring conditions and then ultrasonic to prepare colostrum; continue to add chitosan solution to colostrum and stir, after stirring, remove the solvent to obtain the nanoemulsion preparation.

In some embodiments, the mixed oil of angelica volatile oil and chuanxiong volatile oil is extracted by supercritical extraction method.

In some embodiments, the mass ratio of the crude drug raw materials of the Angelica sinensis and the Rhizoma Chuanxiong is 1:0.5-2. -200 mesh sieve, spare.

In some embodiments, during the supercritical extraction process, the system pressure is maintained at 25-45MPa, the system temperature is maintained at 35-55°C, the system carbon dioxide flow rate is maintained at 25-35mL/min, and the extraction is performed 1-3 times, each extraction The time is 1-3h.

In some embodiments, after the supercritical extraction is completed, the extracted liquid is left to stand for 0.5-2 hours.

In some embodiments, chitosan and alginate are used as encapsulating materials. Under stirring conditions, the ethanol solution of mixed oil is first added to the alginate solution of alginate, water and surfactant to prepare the initial milk, and then continue to add chitosan solution to the colostrum and stir, and then evaporate to remove the solvent to prepare a nanoemulsion preparation.

In some embodiments, the chitosan has a molecular weight of 50-150 kDa, the chitosan solution is a solution obtained by adding chitosan to water, and the concentration of the chitosan solution is 0.1-1 mg/mL.

In some embodiments, the alginate is sodium alginate of brown seaweed, the alginate solution is a solution obtained by adding alginate to water and a surfactant, and the concentration of the alginate solution is 0.3-1mg/mL.

In some embodiments, the ethanol solution of the mixed oil is a solution obtained by mixing the mixed oil of the volatile oil of Angelica sinensis and the volatile oil of Ligusticum chuanxiong with ethanol, and the concentration of the ethanol solution of the mixed oil is 10-20 mg/mL.

In some embodiments, the ultrasound for preparing colostrum is probe ultrasound, and the ultrasound time is 10-30 minutes.

In some embodiments, the solvent is removed by evaporation using a rotary evaporator at a temperature of 40-60° C. for 10-30 minutes.

The present disclosure also provides the above nanoemulsion preparation for treating migraine or the nanoemulsion preparation for treating migraine prepared by the above preparation method for preparing functional food or medicine for treating migraine.

In some embodiments, the nanoemulsion formulation is used to prepare a medicament for preventing migraine.

The present disclosure also provides a product for treating migraine, the raw materials of which include the above-mentioned nanoemulsion for treating migraine or the nanoemulsion for treating migraine prepared by the above preparation method, and the product includes any of the

The present disclosure also provides a medicament for treating migraine, which includes the nanoemulsion for treating migraine as described in any one of the above or the nanoemulsion for treating migraine prepared by any of the preparation methods described above preparation.

The present disclosure also provides a method for treating migraine-related diseases, comprising: administering a therapeutically effective amount of the antibacterial drug to a subject in need thereof.

The present disclosure also provides the nanoemulsion preparation for treating migraine described in any one of the above or the nanoemulsion preparation for treating migraine prepared by the preparation method described in any one of the above or the product or the drug in Use for treating diseases associated with migraine.

The present disclosure also provides the nanoemulsion preparation for treating migraine described in any one of the above or the nanoemulsion preparation for treating migraine prepared by any of the preparation methods described above or the product or the drug, Use for treating diseases associated with migraine.

In some embodiments, the migraine-related diseases include: migraine without aura, migraine with aura, childhood recurrent syndrome with prodromal migraine, retinal migraine, chronic migraine, status migraine, At least one of persistent aura of infarction, migraineous infarction, and migraine-induced seizures.

Description of drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the following will briefly introduce the accompanying drawings used in the embodiments. It should be understood that the following drawings only show some embodiments of the present disclosure, and therefore are not It should be regarded as a limitation on the scope, and those skilled in the art can also obtain other related drawings based on these drawings without creative work.

Fig. 1 is the particle size distribution figure of Chinese medicine nanoemulsion preparation in Experimental Example 1;

Fig. 2 is the morphology figure of Chinese medicine nanoemulsion preparation in Experimental Example 1;

Fig. 3 is a schematic diagram of mouse modeling and administration time in Experimental Example 2;

Figure 4 is a graph showing the effect of different concentrations of traditional Chinese medicine nanoemulsion preparations on the latent pain response of migraine mice on the hot plate in Experimental Example 2, ^# p<0.05, ^## p<0.01, ^* p<0.05, ^** p<0.01 ;

Figure 5 is the effect of different concentrations of traditional Chinese medicine nanoemulsion preparations on the formalin-guided paw licking response of migraine mice in Experimental Example 2, ^# p<0.05, ^## p<0.01, ^* p<0.05, ^** p <0.01;

Figure 6 is a graph showing the effect of different concentrations of traditional Chinese medicine nanoemulsion preparations on the acetic acid-induced writhing response of migraine mice in Experimental Example 2, ^# p<0.05, ^## p<0.01, ^* p<0.05, ^** p<0.01;

Figure 7 is a graph showing the effect of different concentrations of traditional Chinese medicine nanoemulsion preparations on the blood CGRP content of migraine mice in Experimental Example 2, ^# p<0.05, ^## p<0.01, ^* p<0.05, ^** p<0.01;

Figure 8 is a graph showing the effect of different concentrations of traditional Chinese medicine nanoemulsion preparations on the blood 5-HT content of migraine mice in Experimental Example 2, ^# p<0.05, ^## p<0.01, ^* p<0.05, ^** p<0.01;

Figure 9 is a graph showing the effect of different concentrations of traditional Chinese medicine nanoemulsion preparations on blood NO levels in migraine mice in Experimental Example 2, ^# p<0.05, ^## p<0.01, ^* p<0.05, ^** p<0.01.

Detailed ways

In order to make the objectives, technical solutions and advantages of the embodiments and examples of the present disclosure clearer, the technical solutions in the embodiments and examples of the present disclosure will be clearly and completely described below. Where specific conditions are not indicated in the implementation modes and examples, proceed according to conventional conditions or conditions suggested by the manufacturer. The reagents or instruments used were not indicated by the manufacturer, and they were all conventional products that could be purchased from the market.

The disclosure provides a method for preparing a traditional Chinese medicine nanoemulsion preparation for treating migraine. The method is simple, easy to operate and low in cost, and can effectively prepare the traditional Chinese medicine nanoemulsion preparation from angelica and chuanxiong.

One embodiment of the present disclosure provides a traditional Chinese medicine nanoemulsion preparation for treating migraine. The volatile oil of Angelica sinensis and the volatile oil of Chuanxiong Rhizoma Rhizoma Chuanxiong are used as effective medicinal ingredients together with acceptable auxiliary ingredients in the medicine. The effective medicinal ingredients are obtained from supercritical extraction of Angelica sinensis and Rhizoma Chuanxiong with a weight ratio of 1:0.5-2.

In an optional embodiment, the volatile oil of Angelica Sinensis and the volatile oil of Rhizoma Chuanxiong are used as effective pharmaceutical ingredients, and polysaccharide biomacromolecules are used as encapsulation materials to encapsulate the volatile oil of Angelica Sinensis and the volatile oil of Rhizoma Chuanxiong in the presence of surfactants and co-surfactants. , made into nanoemulsions.

In an optional embodiment, the active pharmaceutical ingredients are obtained by extracting and separating the volatile oil of Angelica Sinensis and the volatile oil of Rhizoma Chuanxiong by means of supercritical carbon dioxide circulation countercurrent;

In some embodiments, when supercritical carbon dioxide circulates and countercurrently extracts the volatile oil, the two crude drug raw materials of Angelica sinensis and Rhizoma Chuanxiong are mixed and then extracted simultaneously;

In some embodiments, the polysaccharide biomacromolecule is selected from including but not limited to alginate and chitosan;

In some embodiments, the surfactant is selected from including but not limited to Tween-80 (Tween-80), polyethylene glycol octylphenyl ether-100 (TritonX-100), sucrose fatty acid ester fatty acyl At least one of Ninol.

In an optional embodiment, the average particle size of the traditional Chinese medicine nanoemulsion preparation is 150-300 nm. In an optional embodiment, the particle size of the traditional Chinese medicine nanoemulsion preparation is 200-300Nm.

In an optional embodiment, the average particle size of the traditional Chinese medicine nanoemulsion preparation is 180-220 nm. In some embodiments, the average particle size of the traditional Chinese medicine nanoemulsion preparation can be, for example, 200-260nm, 210-290nm, 220-280nm, such as 200nm, 210nm, 220nm, 230nm, 240nm, 250nm, 260nm, 270nm, 280nm, 290nm, 300nm.

In an optional embodiment, the potential of the traditional Chinese medicine nanoemulsion preparation is 30-60mV. In some embodiments, the potential of the traditional Chinese medicine nanoemulsion preparation is such as 30mV, 35mV, 40mV, 45mV, 50mV, 55mV, 60mV.

In an optional embodiment, the polymer dispersion index of the traditional Chinese medicine nanoemulsion preparation is 0.1-0.2. In some embodiments, the polymer dispersion index of the traditional Chinese medicine nanoemulsion preparation is such as 0.1, 0.12, 0.13, 0..14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2.

One embodiment of the present disclosure also provides a method for preparing a traditional Chinese medicine nanoemulsion preparation for treating migraine, which includes the following steps: extract the mixed powder of Angelica root and Chuanxiong root by supercritical extraction, collect the mixed volatile oil of the two, and then use Chitosan and alginate were used as loading materials, and nanoemulsion preparations were prepared by single-emulsion solvent evaporation method.

In an optional embodiment, the single emulsification solvent evaporation method comprises the following steps: mixing the mixed oil of the volatile oil of Angelica sinensis and the volatile oil of Ligusticum chuanxiong with ethanol as the oil phase, and mixing the alginate with water and surfactant as the water phase, and stirring Next, the above-mentioned oil phase is added to the water phase, and then ultrasound is performed to obtain colostrum; chitosan solution is continuously added to the colostrum and stirred, and after the stirring is completed, the solvent is evaporated to obtain the nanoemulsion preparation .

In an optional embodiment, the single-emulsion solvent evaporation method includes the following steps: using chitosan and alginate as encapsulating materials, under stirring conditions, firstly add the ethanol solution of the mixed oil to the alginate, water and surface The colostrum is prepared in the alginate solution of the active agent, then the chitosan solution is continuously added to the colostrum and stirred, and the solvent is evaporated to remove the solvent to prepare the nanoemulsion preparation.

In an optional embodiment, the essential oils in Angelica Sinensis and Rhizoma Chuanxiong are extracted by supercritical extraction.

In an optional embodiment, 100-200 g of Angelica sinensis and 100-200 g of Rhizoma Chuanxiong are selected.

In an optional embodiment, in the process of selecting Angelica sinensis and Rhizoma Chuanxiong, the mass ratio of Angelica sinensis and Rhizoma Chuanxiong is 1:0.5-2.

In an optional embodiment, before selecting Angelica sinensis and Chuanxiong, it also includes grinding the Angelica and Chuanxiong.

In an optional embodiment, the pulverizing treatment is to pulverize the Angelica sinensis and Ligusticum chuanxiong with a pulverizer, and then obtain their pulverized products.

In an optional embodiment, the crushed products of Angelica sinensis and Rhizoma Chuanxiong need to pass through a 50-200 mesh sieve.

In an optional embodiment, during the supercritical extraction process, the system pressure is maintained at 25-45 MPa.

In an alternative embodiment, during the supercritical extraction, the system temperature is maintained at 35-55°C.

In an optional embodiment, during the supercritical extraction process, the flow rate of carbon dioxide in the system is maintained at 25-35 mL/min.

In an optional embodiment, the supercritical extraction is extracted 1-3 times under the condition of 1-3 hours.

In an optional embodiment, after the extraction is completed, it also includes standing the extracted liquid for 0.5-2 hours.

In an alternative embodiment, chitosan and alginate are used as materials for loading the nanoemulsion with volatile oil.

In an alternative embodiment, chitosan and alginate materials are used for loading.

In an alternative embodiment, the chitosan is selected to be 50-150 kDa.

In an alternative embodiment, the alginate is sodium alginate selected from brown seaweed.

In an alternative embodiment, the nanoemulsion is prepared using a single emulsion solvent evaporation method.

In an optional embodiment, during the preparation process, the chitosan solution is a solution obtained by adding chitosan to water, and the chitosan solution is 0.1-1 mg/mL.

In an optional embodiment, during the preparation process, the alginate solution is a solution obtained by adding alginate to water and a surfactant, and the alginate solution is 0.3-1 mg/mL.

In an optional embodiment, during the preparation process, the ethanol solution of the mixed oil is a solution obtained by mixing the mixed oil of Angelica volatile oil and Chuanxiong volatile oil with ethanol, and the concentration of the mixed oil ethanol solution is 10-20 mg/mL.

In an optional embodiment, the ultrasound for preparing the colostrum is probe ultrasound, and the ultrasound time is 10-30 minutes.

In an optional embodiment, solvent evaporation is performed by using a rotary evaporator at a temperature of 40-60° C. for 10-30 minutes.

One embodiment of the present disclosure also provides the application of the traditional Chinese medicine nanoemulsion preparation as in the foregoing embodiment, and the traditional Chinese medicine nanoemulsion preparation is used for preparing food or medicine for treating migraine.

In an optional embodiment, the traditional Chinese medicine nanoemulsion preparation is used to prepare a medicine for treating migraine.

The present disclosure also provides a food, the raw material of which includes the traditional Chinese medicine nanoemulsion preparation of the aforementioned embodiment.

The present disclosure provides a medicine for treating migraine, the raw material of which includes the traditional Chinese medicine nanoemulsion preparation of the aforementioned embodiment.

The traditional Chinese medicine nanoemulsion preparation provided by the present disclosure and its preparation method and application will be described below.

The disclosure proposes a method for preparing a traditional Chinese medicine nano-emulsion preparation for treating migraine, which includes the following steps: extract the mixed powder of angelica root and chuanxiong root by supercritical extraction method, collect volatile oil, and then use chitosan and alginate as Materials, nanoemulsion preparations were prepared by single emulsification solvent evaporation method.

Among them, choose Angelica 100-200g, Chuanxiong 100-200g. In some embodiments, the selected angelica mass can be 100g, 125g, 150g, 175g or 200g, or any other value within the range of 100-200g. The selected mass of Ligusticum chuanxiong can be 100g, 125g, 150g, 175g or 200g, or any other value within the range of 100-200g.

In the above-mentioned process of selecting angelica and chuanxiong, the mass ratio of angelica and chuanxiong can be 1:0.5-2, such as 1:0.5, 1:0.7, 1:0.75, 1:1, 1:1.2, 1:1.4, 1:1.5 , 1:1.6, 1:1.8, or 1:2, etc., or any other value within the range of 1:0.5-2.

In an optional embodiment, 200 g of Angelica sinensis and 100 g of Rhizoma Chuanxiong are selected, and the mass ratio of Angelica sinensis and Rhizoma Chuanxiong is 1:0.5.

In an optional embodiment, before selecting the Angelica sinensis and the Rhizoma Chuanxiong, it also includes grinding the Angelica sinensis and the Rhizoma Chuanxiong. For reference, the milling treatment is to pulverize the Angelica sinensis and Chuanxiong Rhizoma Rhizoma Chuanxiong through a mill, and then obtain pulverized products. Among them, the pulverized products of angelica and chuanxiong need to pass through a 50-200 mesh sieve, such as 50 mesh, 100 mesh, 150 mesh or 200 mesh, etc., or any other value within the range of 50-200 mesh. In some embodiments, the pulverized products of Angelica sinensis and Rhizoma Chuanxiong can pass through a 100-mesh sieve, and the angelica sinensis and Rhizoma Chuanxiong can be fully processed before extraction within the above optional condition range.

In a typical implementation, Guigen and Ligusticum Rhizoma Chuanxiong roots are first dried and pulverized before supercritical extraction treatment. Pulverization can increase the contact area between the raw material and the extractant, thereby increasing the dissolution rate of the functional ingredients.

Alternatively, the essential oils are extracted using supercritical extraction.

In an optional embodiment, the system pressure is maintained at 25-45MPa (such as 25MPa, 30MPa, 35MPa, 40MPa or 45MPa, such as 35MPa), and the system temperature is maintained at 35-55°C (such as 35°C, 40°C, 45°C, 50°C or 55°C, such as 45°C), and the system carbon dioxide flow rate is maintained at 25-35mL/min (such as 25mL/min, 30mL/min or 35mL/min, such as 30mL/min), the supercritical extraction time is 1 -3h (such as 1h, 1.5h, 2h, 2.5h or 3h, such as 3h) conditions to extract 1-3 times (such as 1 time, 2 times or 3 times, such as 3 times).

Subsequently, the extracted liquid is left standing for 0.5-2h, such as 0.5h, 1h, 1.5h or 2h, and in some embodiments, the standing time is 2h.

Alternatively, chitosan and alginate were used as materials for volatile oil-loaded nanoemulsions.

In an alternative embodiment, chitosan and alginate materials are used for loading. Chitosan is selected to be 50-150 kDa (eg, 50 kDa, 100 kDa or 150 kDa, in some embodiments, chitosan is 50 kDa). In addition, the alginate is sodium alginate derived from brown seaweed.

Alternatively, the nanoemulsion is prepared using the single emulsion solvent evaporation method. In the process of nanoemulsion preparation, chitosan and alginate are used as coating materials. On the one hand, these two materials are naturally non-toxic, low in price, and have good biocompatibility. The reason for adding chitosan and alginate in stages is that the alginate in the inner layer of the oil is negatively charged, and the chitosan in the outer layer is positively charged. The whole material is tightly combined by electrostatic force, so that the mixed volatile oil It can be well coated to form nanoemulsion preparations.

In an optional embodiment, the single emulsification solvent evaporation method can use a chitosan solution of 0.1-1mg/mL (such as 0.1mg/mL, 0.25mg/mL, 0.5mg/mL, 0.75mg/mL or 1mg/mL In some embodiments, chitosan solution is 0.5mg/mL), and alginate solution is 0.3-1mg/mL (such as 0.3mg/mL, 0.6mg/mL, 0.9mg/mL or 1mg/mL. In In some embodiments, the alginate solution is 0.6 mg/mL), and the ethanol solution containing the volatile oil of traditional Chinese medicine is 10-20 mg/mL (such as 10 mg/mL, 15 mg/mL or 20 mg/mL. In some embodiments, the Chinese medicine containing The ethanol solution of volatile oil is 20mg/mL).

Subsequently, the ultrasound for preparing colostrum is probe ultrasound, and the ultrasound time is 10-30 minutes (such as 10 minutes, 15 minutes, 20 minutes, 25 minutes or 30 minutes. In some embodiments, the ultrasound time is 15 minutes).

Optionally, the colostrum can be purified by a solvent evaporation method, and a rotary evaporator is used to obtain a purified traditional Chinese medicine nanoemulsion preparation.

In an optional embodiment, the set temperature of the rotary evaporator instrument is 40-60°C (such as 40°C, 45°C, 50°C, 55°C or 60°C. In some embodiments, the set temperature of the rotary evaporator instrument is 60°C °C), and the duration is 10-30 min (eg, 10 min, 15 min, 20 min, 25 min or 30 min, in some embodiments, the duration is 20 min).

The above preparation process can refer to: Angelica sinensis 100-200g and Chuanxiong 100-200g. Carry out powder treatment, and transfer to supercritical extractor to extract volatile oil through 100 mesh sieve, under the condition that the system pressure is maintained at 25-45MPa, the temperature is maintained at 35-55°C, and the flow rate of carbon dioxide is maintained at 25-35mL/min. The critical extraction time is to extract 3 times under the condition of 3 hours. After the extraction is completed, it also includes standing the extracted liquid for 0.5-2h. Then the loading was carried out using chitosan and alginate materials. 50kDa chitosan and sodium alginate derived from brown seaweed were selected. Nanoemulsions were prepared using the single emulsion solvent evaporation method. In some embodiments, the chitosan solution is 0.1-1mg/mL, the alginate solution is 0.3-1mg/mL, the ultrasound for preparing colostrum is probe ultrasound, and the ultrasound time is 10-30min. Steam instrument, the temperature is 40-60°C, and the duration is 10-30min.

It is worth noting that the above-mentioned extraction and preparation steps in the present disclosure do not exclude other existing conventional extraction and preparation methods, which will not be repeated here.

Correspondingly, the present disclosure also provides a traditional Chinese medicine nanoemulsion preparation prepared by the above extraction and preparation method.

The particle size of the obtained traditional Chinese medicine nanoemulsion preparation is about 200-300nm, the potential is about 30-60mV, and the polymer dispersion index is about 0.1-0.2 through analysis by the dynamic light scattering method of the Malvern particle size analyzer.

In addition, the present disclosure also provides the application of the above-mentioned traditional Chinese medicine nanoemulsion preparation, such as for preparing food or medicine for treating migraine.

In an optional embodiment, the traditional Chinese medicine nanoemulsion preparation is used to prepare a medicine for treating migraine.

Optionally, the present disclosure also provides a food whose raw material includes the above-mentioned traditional Chinese medicine nanoemulsion preparation. For reference, the above-mentioned foods may include milk and dairy products, fat products, frozen drinks, grain products, baked foods, meat products, egg products, nutritious foods, functional foods or beverages, etc. In addition, other types of food.

The present disclosure also provides a medicine for treating migraine, the raw material of which includes the above-mentioned traditional Chinese medicine nanoemulsion preparation. Using the above-mentioned traditional Chinese medicine nanoemulsion preparation as a drug raw material can make the drug have the advantages of safety, definite effect and less adverse reactions.

The present disclosure also provides a medicine for treating migraine, which comprises a nanoemulsion preparation for treating migraine or a nanoemulsion preparation for treating migraine prepared by the above preparation method.

The present disclosure also provides a method for treating migraine-related diseases, comprising: administering a therapeutically effective amount of the antibacterial drug to a subject in need thereof.

The present disclosure also provides the use of the nanoemulsion preparation for treating migraine or the nanoemulsion preparation or product or medicine for treating migraine prepared by the above preparation method in treating diseases related to migraine.

The present disclosure also provides the nanoemulsion preparation for treating migraine or the nanoemulsion preparation or product or medicine for treating migraine prepared by the above-mentioned preparation method for treating diseases related to migraine.

In some embodiments, migraine-related disorders include: migraine without aura, migraine with aura, childhood recurrent syndrome with prodromal migraine, retinal migraine, chronic migraine, status migraine, non-infarcted At least one of persistent aura, migraine infarction, and migraine-induced seizures.

The traditional Chinese medicine nanoemulsion preparation has good analgesic effect and neurovascular activity, can alleviate and treat migraine, can reduce the attack intensity and frequency of migraine mice, and reduce disease-related biochemical indexes. The effects of the above-mentioned traditional Chinese medicine nanoemulsion preparations on migraine may be related to the regulation of pain signal transmission, intestinal flora and neurovascular system. In addition, the drug delivery materials chitosan and alginate have good controlled release effect and high bioaffinity as drug carriers.

The traditional Chinese medicine nanoemulsion preparation provided by the disclosure can relieve migraine by regulating the levels of migraine-related biochemical indicators, interfering with pain signal transduction pathways, and regulating the abundance of intestinal flora, and can also be combined with other drugs for comprehensive treatment.

The disclosure provides a traditional Chinese medicine nanoemulsion preparation with a better effect on treating migraine and its preparation method and application. The Chinese medicine nanoemulsion preparation provided by the disclosure uses angelica volatile oil and Chuanxiong volatile oil as effective pharmaceutical ingredients, and is compatible with pharmaceutically acceptable Auxiliary additive ingredients are jointly composed, and the effective pharmaceutical ingredients are obtained from the supercritical extraction of angelica and chuanxiong with a weight ratio of 1:0.5-2. Among them, the active pharmaceutical ingredients are extracted and separated by means of supercritical carbon dioxide circulation and countercurrent. And the above-mentioned volatile oil is encapsulated in the polysaccharide biomacromolecule to obtain the nanoemulsion preparation. The experimental effect is ideal. The prepared Chinese medicine nanoemulsion preparation at least has the effect of relieving migraine, and can reduce the intensity and frequency of attacks in migraine mice. , reducing disease-related biochemical indices, providing a scientific basis for its application in the preparation of food or medicine for treating migraine.

The features and properties of the present disclosure will be described in detail below in conjunction with the embodiments.

In the following examples of the present disclosure, the sources of raw materials, components, preparation and experimental methods are the same as those of the comparative examples.

Example

Example 1

The present embodiment provides a kind of preparation method of the Chinese medicine nanoemulsion preparation for the treatment of migraine:

(1) Select 200g of Angelica sinensis and 100g of Rhizoma Chuanxiong, grind them into 100-mesh fine powder, mix them evenly at a mass ratio of 1:0.5, and set aside.

(2) Then by supercritical extraction method, extract under the conditions of pressure 35MPa and temperature 45°C, the extraction time is 2 hours, the number of extractions is 1 time, and the flow rate of carbon dioxide is 30mL/min to obtain the volatile oil of traditional Chinese medicine, which is ready for use.

(3) Select the materials of chitosan and alginate, the alginate is to choose sodium alginate derived from brown seaweed, the alginate solution is to add 6mg of alginate to 20mL of distilled water, then add 0.2g Put Tween-80 in the solution to obtain the water phase, that is, a 0.3mg/mL alginate solution; the oil phase is to add 12mg of Chinese medicine volatile oil to 0.6mL ethanol solution, to obtain the oil phase, that is, a 20mg/mL oily ethanol solution; chitosan To select the relative molecular mass of 50kDa, the chitosan solution is to add 0.4mg of chitosan to 4mL of distilled water to obtain a chitosan solution of 0.1mg/mL. The steps of the single emulsification solvent evaporation method are as follows: first, the prepared oily ethanol solution is added drop by drop to the aqueous alginate solution, and at the same time, it needs to be stirred, and then the probe is ultrasonicated. The ultrasonic time is 10 minutes and stirred for 30 minutes to obtain colostrum. Then add chitosan solution, stir for 30 minutes, and evaporate the solvent by using a rotary evaporator at a temperature of 40° C. for 10 minutes, and equilibrate overnight to obtain a nanoemulsion preparation loaded with volatile oil of traditional Chinese medicine, and complete the preparation.

Example 2

The present embodiment provides a kind of preparation method of the Chinese medicine nanoemulsion preparation for the treatment of migraine:

(1) Select 150g of Angelica sinensis and 150g of Rhizoma Chuanxiong, grind them into 50-mesh fine powder, mix them evenly at a mass ratio of 1:1, and set aside.

(2) Then by the supercritical extraction method, extract under the conditions of pressure 40MPa and temperature 40°C, the extraction time is 3 hours, the number of extractions is 1 time, and the flow rate of carbon dioxide is 25mL/min to obtain the volatile oil of traditional Chinese medicine for future use.

(3) Select the materials of chitosan and alginate, the alginate is to choose sodium alginate derived from brown seaweed, the alginate solution is to add 12mg of alginate to 20mL of distilled water, then add 0.2g Put Tween-80 in the solution to obtain the water phase, that is, a 0.6mg/mL alginate solution; the oil phase is to add 12mg of Chinese medicine volatile oil to 0.6mL ethanol solution, to obtain the oil phase, that is, a 20mg/mL oily ethanol solution; chitosan To select the relative molecular mass of 100kDa, the chitosan solution is to add 2mg of chitosan to 4mL of distilled water to obtain a chitosan solution of 0.5mg/mL. The steps of the single emulsification solvent evaporation method are as follows: first, add the prepared oil-containing ethanol solution drop by drop into the aqueous alginate solution, and at the same time, it needs to be stirred, and then the probe is ultrasonicated. Then add chitosan solution, stir for 30 minutes, and evaporate the solvent by using a rotary evaporator at a temperature of 50° C. for 20 minutes, and equilibrate overnight to obtain a nanoemulsion preparation loaded with volatile oil of traditional Chinese medicine, and complete the preparation.

Example 3

The present embodiment provides a kind of preparation method of the Chinese medicine nanoemulsion preparation for the treatment of migraine:

(1) Select 100g of Angelica sinensis and 200g of Rhizoma Chuanxiong, grind them into 200 mesh fine powder, mix them evenly at a mass ratio of 1:2, and set aside.

(2) Then by supercritical extraction, extract under the conditions of a pressure of 30 MPa and a temperature of 50°C, the extraction time is 2 hours, the number of extractions is 2 times, and the flow rate of carbon dioxide is 35mL/min to obtain the Chinese medicine volatile oil for future use.

(3) Select the materials of chitosan and alginate, the alginate is to choose sodium alginate derived from brown seaweed, the alginate solution is to add 18mg of alginate to 20mL of distilled water, then add 0.2g Put Tween-80 in the solution to obtain the water phase, which is a 0.9mg/mL alginate solution; the oil phase is to add 12mg of Chinese medicine volatile oil to 0.6mL ethanol solution to obtain the oil phase, which is a 20mg/mL oil-containing ethanol solution; chitosan To select a relative molecular mass of 150kDa, the chitosan solution is to add 4mg of chitosan to 4mL of distilled water to obtain a chitosan solution of 1mg/mL. The steps of the single emulsification solvent evaporation method are as follows: first, add the prepared oil-containing ethanol solution drop by drop into the aqueous alginate solution, and at the same time, it needs to be stirred. Then add chitosan solution, stir for 30 minutes, and evaporate the solvent by using a rotary evaporator at a temperature of 60° C. for 30 minutes, and equilibrate overnight to obtain a nanoemulsion preparation loaded with volatile oil of traditional Chinese medicine, and complete the preparation.

Experimental example 1

Particle size distribution and transmission electron microscope morphology analysis of traditional Chinese medicine nanoemulsion preparations

The particle size distribution and morphology analysis of the traditional Chinese medicine nanoemulsion prepared in Example 1 were measured by the dynamic light scattering method of the Malvern particle size analyzer. About 50 μ L of the sample was taken and put into a potentiometer for measurement. The scattering angle was 90 degrees and the temperature was controlled. is 25°C.

The results are shown in Figure 1: the particle size of the obtained Chinese medicine nanoemulsion preparation is about 200-300nm, the potential is about 30-60mV, and the polymer dispersion index is about 0.1-0.2.

The result is shown in Figure 2: the morphology of the obtained Chinese medicine nanoemulsion preparation is spherical.

Experimental example 2

The therapeutic effect of traditional Chinese medicine nanoemulsion preparation on migraine

(1) animals

Twenty-five female SPF-grade C57BL/6J mice, weighing 17-24 g, were provided by Guangdong Medical Experimental Animal Center.

(2) Grouping and modeling

The animals were randomly divided into 5 groups, the control group, the model group, the positive control group, the low-dose Chinese medicine nanoemulsion group, and the high-dose Chinese medicine nanoemulsion group, with 5 animals in each group. All the mice were fed adaptively for one week and then the test was started. From the 0th day, each dose group of the traditional Chinese medicine nanoemulsion was orally administered with doses of 52 and 104 mg/kg, respectively, and the control group, model group, and positive control group were given corresponding volumes of Gastrointestinal administration of distilled water, the end of the seventh day, pre-administration for 1 week. In the positive control group, the positive drug sumatriptan (sumatriptan) was injected intraperitoneally at a dose of 0.6 mg/kg at the last administration. Using nitroglycerin to induce a migraine mouse model, by subcutaneously injecting nitroglycerin at a dose of 10 mg/kg, the migraine animal model was successfully established 30 minutes later. The above-mentioned traditional Chinese medicine nanoemulsion preparation is the traditional Chinese medicine nanoemulsion preparation prepared in Example 1.

(3) Behavioral tests of mice

Experiments included hot plate latency pain response test, formalin induced foot licking test and acetic acid induced twisting test.

During the hot-plate latent pain response experiment, firstly, female mice were placed on a hot plate at 55±0.5°C, and their pain responses (paw licking or jumping) were observed. Each mouse was habituated to the hot plate twice prior to the experiment. The latency time before the onset of pain response was recorded as an analgesic parameter. Untreated mice with background potential response times shorter than 10 s or longer than 30 s were excluded from this study. For hot plates, animals must be retrieved immediately after a response is observed. For all tests, a cutoff time of 60 s was defined to avoid or limit the risk of burns. One measurement was taken as a baseline before administration, and the hot plate latency of each animal was recorded at 30, 60, 90, and 120 minutes after administration. The analgesic effect was evaluated by recording the hot plate latency reaction time.

During the formalin-induced paw licking experiment, female C-57 mice were used to subcutaneously inject 5% formalin solution into the dorsal skin of the right hind paw. After the injection was completed, the mice were placed on a 27°C hot plate. In , record the total licking time within 5 minutes. The analgesic effect was assessed by recording the formalin-stimulated paw licking time.

During the acetic acid-induced twisting experiment, a writhing model was established by intraperitoneally injecting 0.6% acetic acid aqueous solution (0.1 mL/10 g) using female C-57 mice. When the writhing index is the characteristic reaction of concave abdomen, twisting of the trunk, stretching of the hind legs, and raising of the buttocks, it is considered a complete writhing when all the above actions are completed. Each mouse was placed in a transparent observation box, and the number of writhing movements was counted within 15 min after the injection of acetic acid. The analgesic effect was assessed by recording the number of writhing times stimulated by acetic acid.

See Figure 3 for a schematic diagram of mouse modeling and administration time in Experimental Example 2.

From the results of hot plate latency in Figure 4, within 30-120min, the hot plate latency of the model group was significantly lower than that of the control group ( ^# p<0.05, ^## p<0.01). And within 60-120min, compared with the model group, the high-dose TCM nanoemulsion group significantly increased ( ^* p<0.05, ^** p<0.01), and it was dose-dependent.

From the results of formalin-induced foot-licking time in Figure 5, the formalin-induced foot-licking time in the model group was significantly higher than that in the control group ( ^# p<0.05, ^## p<0.01). Compared with the model group, the high-dose Chinese medicine nanoemulsion group improved significantly ( ^* p<0.05, ^** p<0.01), and it was dose-dependent.

From the results of the number of twists caused by acetic acid in Figure 6, the number of twists caused by acetic acid in the model group was significantly higher than that in the control group ( ^# p<0.05, ^## p<0.01). Compared with the model group, the high-dose Chinese medicine nanoemulsion group improved significantly ( ^* p<0.05, ^** p<0.01), and it was dose-dependent.

(4) Changes in biochemical indicators related to migraine

In this experiment, the contents of calcitonin gene-related peptide (CGRP), serotonin (5-HT) and nitric oxide (NO) in blood of mice were determined. First anesthetize the mouse, inject 3.5mL/kg of 10% chloral hydrate solution into the intraperitoneal cavity, and then collect the blood by picking the eyeball, then centrifuge and take the supernatant, and perform CGRP, 5-HT, NO content determination.

The results are shown in Figure 7 to Figure 9: Compared with the blank group, the CGRP and NO content of the model group increased significantly, and the 5-HT content of the model group decreased significantly ( ^# p<0.05, ^## p<0.01) , and compared with the model group, the high-dose Chinese medicine nanoemulsion group could significantly reduce the levels of CGRP and NO in the blood, and increase the levels of 5-HT ( ^* p<0.05, ^** p<0.01).

Comparative example 1

The procedure is similar to that of Example 1, except that the chitosan solution is replaced by 0.67 mg/mL calcium chloride solution (CaCl ₂ ). The particle diameter of the nanoemulsion preparation obtained by it is 254.8 ± 13.6nm, obviously higher than the nanoemulsion preparation particle diameter 194.3 ± 3.9nm obtained in Example 1, so the chitosan in Example 1 of the present disclosure is used as the encapsulating material better.

Comparative example 2

Similar to the steps of Example 2, the only difference is that a 200 kDa chitosan solution is used. The particle diameter of the nanoemulsion preparation that it obtains is 242.8 ± 4.4nm, obviously higher than the nanoemulsion preparation particle diameter 191.8 ± 5.8nm obtained in Example 2, so it is better to use the chitosan of 100kDa in the embodiment 2 of the present disclosure .

Comparative example 3

Similar to the steps in Example 3, the only difference is that the ultrasound time of the probe is 5 minutes. The particle size of the obtained nanoemulsion is 228.3 ± 2.4nm, which is significantly higher than the particle size of the nanoemulsion obtained in Example 3, which is 190.1 ± 5.4nm. Therefore, the ultrasonic time of the probe in Example 3 of the present disclosure is 30min. .

Comparative example 4

Similar to the steps of Example 1, the only difference is that a 0.6 mg/mL alginate solution is used. The particle size of the obtained nanoemulsion is 215.8±4.4nm, which is significantly higher than the particle size of the nanoemulsion obtained in Example 1, which is 194.3±3.9nm, so the alginate solution in Example 1 of the present disclosure is used as the encapsulation The material is better.

Comparative example 5

Similar to the steps of Example 2, the only difference is that a 1 mg/mL chitosan solution is used. The particle diameter of the nanoemulsion preparation obtained by it is 212.0 ± 4.7nm, obviously higher than the nanoemulsion preparation particle diameter 191.8 ± 5.8nm obtained in Example 2, so the chitosan solution in the embodiment 2 of the present disclosure is used as the encapsulation The material is better.

To sum up, the embodiment of the present disclosure provides a traditional Chinese medicine nanoemulsion preparation for treating migraine and its preparation method and application. The embodiment of the present disclosure provides a traditional Chinese medicine nanoemulsion preparation for treating migraine. The preparation method includes the following steps: Angelica and Chuanxiong were selected; the volatile oil of traditional Chinese medicine was extracted by supercritical extraction method; chitosan and alginate were selected, and the volatile oil of traditional Chinese medicine was loaded by single emulsification solvent evaporation method to complete the preparation of nanoemulsion. The traditional Chinese medicine nanoemulsion preparation prepared by the above method has ideal application effect, can effectively treat the headache symptoms of migraine mice, reduce disease-related biochemical indicators, have the effect of relieving migraine symptoms, and can be prepared into food or migraine medicine for treatment.

The preparation method of the traditional Chinese medicine nanoemulsion preparation provided by the embodiment of the present disclosure is simple, easy to operate, and low in cost, and can effectively extract volatile oil from angelica and chuanxiong. The prepared traditional Chinese medicine nanoemulsion has at least the effect of relieving migraine, can reduce the intensity and frequency of attacks in mice with migraine, and reduce the biochemical index related to the disease, which provides a good foundation for its application in the preparation of food or drugs for the treatment of migraine. scientific basis.

The above are only optional embodiments of the present disclosure, and are not intended to limit the present disclosure. For those skilled in the art, the present disclosure may have various modifications and changes. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present disclosure shall be included within the protection scope of the present disclosure.

Industrial Applicability

The disclosure provides a traditional Chinese medicine nanoemulsion preparation with a better effect on treating migraine and its preparation method and application. The prepared Chinese medicine nanoemulsion preparation at least has the effect of relieving migraine, and can reduce the attack intensity and frequency of migraine mice , reducing disease-related biochemical indexes, providing a scientific basis for its application in preparing food or treating migraine, and has excellent application value.

Claims (16)

A nanoemulsion preparation for treating migraine, characterized in that the volatile oil of Angelica sinensis and the volatile oil of Chuanxiong Rhizoma are used as effective pharmaceutical ingredients, and are composed of acceptable auxiliary ingredients in medicine, wherein the effective pharmaceutical ingredients are derived from Angelica sinensis and Rhizoma Chuanxiong. The weight ratio is 1:0.5-2 for supercritical extraction. The nanoemulsion preparation for the treatment of migraine according to claim 1, characterized in that, taking the volatile oil of Angelica sinensis and the volatile oil of Rhizoma Chuanxiong as active pharmaceutical ingredients, utilizing polysaccharide biomacromolecules as encapsulating materials, and treating Angelica sinensis in the presence of surfactants The mixed oil of volatile oil and chuanxiong volatile oil is encapsulated to make nanoemulsion preparation. The nanoemulsion preparation for the treatment of migraine according to claim 2, wherein the active pharmaceutical ingredient is obtained by extracting and separating Angelica volatile oil and Chuanxiong volatile oil with supercritical carbon dioxide circulation countercurrent; Preferably, when supercritical carbon dioxide circulates and countercurrently extracts the volatile oil, the two crude drug raw materials of angelica and chuanxiong are mixed and extracted simultaneously; Preferably, the polysaccharide biomacromolecule is selected from alginate and chitosan; Preferably, the surfactant is selected from the group consisting of Tween-80 (Tween-80), polyethylene glycol octylphenyl ether-100 (TritonX-100) and sucrose fatty acid ester fatty amide (Ninol) at least one. The nanoemulsion preparation for treating migraine according to any one of claims 1-3, characterized in that, the particle diameter of the nanoemulsion preparation is 150-300nm. The nanoemulsion preparation for treating migraine according to any one of claims 1-3, wherein the particle diameter of the nanoemulsion preparation is 200-300nm, such as 180-220nm; Preferably, the potential of the nanoemulsion preparation is 30-60mV; Preferably, the polymer dispersion index of the nanoemulsion formulation is 0.1-0.2. A preparation method for the nanoemulsion preparation for the treatment of migraine according to any one of claims 1-5, characterized in that it comprises: taking Angelica volatile oil and Ligusticum chuanxiong volatile oil as active pharmaceutical ingredients, by single emulsification solvent evaporation method , preparing the nanoemulsion. The preparation method according to claim 6, characterized in that, comprising the following steps: mixing the mixed oil of Angelica volatile oil and Rhizoma Chuanxiong volatile oil with ethanol as the oil phase, and mixing alginate with water and surfactant as the water phase, stirring Under certain conditions, the above-mentioned oil phase is added to the water phase, and then ultrasound is used to obtain colostrum; chitosan solution is continuously added to the colostrum and stirred, and after the stirring is completed, the solvent is removed to obtain the nanoemulsion preparation. preparation method according to claim 7, is characterized in that, uses supercritical extraction method to extract the mixed oil of angelica volatile oil and chuanxiong volatile oil; Preferably, the raw material mass ratio of the angelica and the Rhizoma Chuanxiong is 1:0.5-2, the Angelica and the Rhizoma Chuanxiong are crushed to obtain a pulverized product, and the pulverized product is passed through a 50-200 mesh sieve, spare; Preferably, during the supercritical extraction process, the system pressure is maintained at 25-45MPa, the system temperature is maintained at 35-55°C, the system carbon dioxide flow rate is maintained at 25-35mL/min, and extraction is performed 1-3 times, each extraction time is 1 -3h; Preferably, after the supercritical extraction is completed, the extracted liquid is left to stand for 0.5-2 hours. preparation method according to claim 7, is characterized in that, uses chitosan and alginate as encapsulating material, under stirring condition, at first the ethanol solution of mixed oil is added into alginate, water and tensio-active agent In the alginate solution, prepare colostrum, then continue to add chitosan solution to the colostrum and stir, then evaporate to remove the solvent, and prepare nanoemulsion preparation; Preferably, the chitosan has a molecular weight of 50-150kDa, the chitosan solution is a solution obtained by adding chitosan to water, and the chitosan solution has a concentration of 0.1-1 mg/mL; Preferably, the alginate is sodium alginate of brown seaweed, the alginate solution is a solution obtained by adding alginate to water and a surfactant, and the concentration of the alginate solution is 0.3-1mg /mL; Preferably, the ethanol solution of the mixed oil is a solution obtained by mixing the mixed oil of Angelica volatile oil and Chuanxiong volatile oil with ethanol, and the concentration of the ethanol solution of the mixed oil is 10-20 mg/mL; Preferably, the ultrasound for preparing colostrum is probe ultrasound, and the ultrasound time is 10-30 minutes; Preferably, the solvent is removed by evaporation using a rotary evaporator, the evaporation temperature is 40-60° C., and the duration is 10-30 minutes. According to the application of the nanoemulsion preparation for treating migraine described in any one of claims 1-5 or the nanoemulsion preparation for treating migraine prepared by the preparation method described in any one of claims 6-9, it It is characterized in that the nanoemulsion preparation is used for preparing functional food or medicine for treating migraine; Preferably, the nanoemulsion preparation is used to prepare a medicine for preventing migraine. A preparation for the treatment of migraine, characterized in that the raw material of the preparation comprises the nanoemulsion preparation for the treatment of migraine according to any one of claims 1-5 or any one of claims 6-9 The nanoemulsion preparation for treating migraine prepared by the preparation method, the product includes any one of medicine and food. A medicine for treating migraine, characterized in that the medicine comprises the nanoemulsion for treating migraine according to any one of claims 1-5 or any one of claims 6-9. The nanoemulsion preparation for the treatment of migraine prepared by the preparation method. A method for treating migraine-related diseases, comprising: administering a therapeutically effective amount of the antibacterial drug of claim 12 to a subject in need thereof. The nanoemulsion preparation for treating migraine as described in any one of claims 1-5 or the nanoemulsion preparation for treating migraine prepared by the preparation method described in any one of claims 6-9 or as claimed Use of the product described in 11 or the medicament as claimed in claim 12 in the treatment of migraine-related diseases. The nanoemulsion preparation for treating migraine as described in any one of claims 1-5 or the nanoemulsion preparation for treating migraine prepared by the preparation method described in any one of claims 6-9 or as claimed The preparation as described in 11 or the medicine as claimed in claim 12 are used for treating diseases related to migraine. The method according to claim 13 or the use according to claim 14 or 15, wherein the migraine-related diseases include: migraine without aura, migraine with aura, and children's periodic migraine with prodromal migraine Syndrome, retinal migraine, chronic migraine, status migraine, persistent aura without infarction, migrainous infarction, migraine-induced epilepsy.

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