CN110075239A - Nanoemulsions and its preparation method and application - Google Patents

Abstract

The invention discloses a nanoemulsion, its preparation method and application. The nanoemulsion was prepared with sandalwood oil, galangal oil, asarum oil, longan oil and borneol as active ingredients, and polyethylene glycol modified with fatty acid as emulsifier. The nanoemulsion obtained by the method of the invention has a small average particle size and uniform distribution. In the present invention, the nanoemulsion is made into a nasal spray or an in-situ gel is added into a nasal gel, which is administered through the nasal cavity to treat ischemic stroke.

Description

Nanoemulsion and its preparation method and use

technical field

The invention relates to a nanoemulsion and its preparation method and application.

Background technique

Kuanxiong aerosol has been included in China's national drug standards (standard number WS ₃ -B-2417-97), and its prescription is composed of asarum oil 23ml, sandalwood oil 70ml, galangal oil 32ml, longan oil 15ml and borneol 22.5ml g. Mix the four kinds of volatile oils, heat to 40°C, add finely ground borneol, dissolve with slight heat, adjust the total amount to 625ml with absolute ethanol, after mixing, fill each bottle with 2ml of volatile oil and seal it into a pressure-resistant aerosol bottle , press into the propellant (difluorodichloromethane) 12g, that is. Kuanxiong aerosol is developed according to the theory of "aroma, warming and dredging" that "takes dredging as the supplement and focuses on dredging". It is an effective prescription for quick-acting pain relief for coronary heart disease and angina pectoris.

CN1732908A discloses a spray containing borneol, which contains 0.48-8% borneol, 0.5-8.3% asarum oil, 1.5-25% sandalwood oil, and 0.7-11.5% galangal oil by weight percentage , 0.32-5.3% permium oil, 0-5% additive, 10-30% ethanol, and fatty acid glyceride prepared from medium-chain C ₈ -C ₁₂ saturated fatty acid in the balance. The aforementioned sprays do not form nano-sized dispersions.

SUMMARY OF THE INVENTION

One object of the present invention is to provide a method for preparing nanoemulsions, which can obtain nanoemulsions with small average particle size and uniform distribution. Further, the obtained nanoemulsion has good stability.

Another object of the present invention is to provide a nanoemulsion with small average particle size and uniform distribution.

Another object of the present invention is to provide the use of the above-mentioned nanoemulsion.

On the one hand, the present invention provides a kind of preparation method of nanoemulsion, comprises the following steps: take sandalwood oil, galangal oil, asarum oil, Piper longum oil and borneol as active ingredient, take the compound shown in formula (I) as emulsification agent to prepare a nanoemulsion,

In formula (I), R is a C6-C30 alkyl group containing at least one hydroxyl group, and PEG represents a polyethylene glycol segment.

According to the preparation method of the present invention, preferably, in formula (I), R is a C10-C25 alkyl group containing at least one hydroxyl group.

According to the preparation method of the present invention, preferably, the emulsifier is polyethylene glycol-12-hydroxystearate, the structure of which is shown in formula (II),

Wherein, PEG represents a polyethylene glycol segment.

According to the preparation method of the present invention, preferably, the ratio α between the mass volume percent concentration of the emulsifier in % (w/v) and the volume concentration of the primary mixture in % (v/v) is 0.3 to 1.0:1 ; Wherein, the primary mixture is composed of sandalwood oil, galangal oil, asarum oil and longicorn oil.

According to the preparation method of the present invention, preferably, comprises the following steps:

(1) Sandalwood oil, galangal oil, Asarum oil, Piper longum oil and Borneolum as active ingredient are formed into an oil phase mixture;

(2) uniformly mixing the emulsifier and the oil phase mixture to obtain the first mixture;

(3) dispersing the auxiliary material in water to obtain an aqueous phase mixture; wherein, the auxiliary material includes an osmotic pressure regulator and/or a preservative;

(4) mixing the aqueous phase mixture with the first mixture to obtain a second mixture;

(5) raising the temperature of the second mixture to 40-60°C, and then cooling down to 15-25°C to obtain a primary nanoemulsion;

(6) After the pH of the primary nanoemulsion is adjusted to 5.5-6.5 with a pH regulator, water is added to constant volume to obtain the nanoemulsion.

According to the preparation method of the present invention, preferably, in step (2), the ratio α between the mass volume percent concentration of the emulsifier in % (w/v) and the volume concentration of the primary mixture in % (v/v) 0.3～1.0:1; Wherein, the primary mixture is composed of sandalwood oil, galangal oil, asarum oil and longicorn oil.

According to the preparation method of the present invention, preferably, in the nanoemulsion, the mass volume percent concentration of the emulsifier is 1.2 to 15% (w/v), and the volume concentration of the primary mixture is 2 to 15% (v/v ).

According to the preparation method of the present invention, preferably, the volume ratio of sandalwood oil, galangal oil, asarum oil and longan oil is 40～65:15～30:10～25:3～20; The total volume of the oil, the asarum oil and the longan oil is 1 ml, and the amount of the borneol is 0.1-0.25 g.

On the other hand, the present invention provides a nanoemulsion obtained by the above preparation method, the average particle diameter of the nanoemulsion is less than 100nm, and the polydispersity index PDI is less than 0.3.

In another aspect, the present invention also provides the use of the nanoemulsion in the preparation of a drug for treating ischemic stroke.

In the method for preparing the nanoemulsion of the present invention, the polyethylene glycol modified by fatty acid is used as the emulsifier, so that the nanoemulsion with small average particle size and uniform distribution can be prepared. Further, the obtained nanoemulsion has good stability.

Description of drawings

Figure 1 shows different concentrations of Average particle size and polydispersity index plots of nanoemulsions formed at HS15.

Figure 2 shows different concentrations of Stability test graph of nanoemulsions formed under HS15.

Detailed ways

The present invention will be further described below in conjunction with specific examples, but the protection scope of the present invention is not limited thereto.

In the present invention, the phase transition temperature means the temperature at which the hydrophilic and lipophilic properties of the surfactant reach an appropriate balance. The average particle size represents the average size of the nanoparticles in the emulsion, usually expressed as a number average particle size.

In the present invention, the sandalwood oil is the volatile oil extracted by steam distillation from the dry heartwood of the sandalwood tree trunk of the plant of the family Zingiberaceae; The oil is the volatile oil extracted by steam distillation from the dry roots and rhizomes of Asarum chinensis, Hancheng Xiyang or Huaxixin; Volatile oil extracted by steam distillation.

＜Preparation method of nanoemulsion＞

The invention adopts the phase transition temperature method to prepare the nanoemulsion. The process has low energy consumption and low cost. The preparation method of the nanoemulsion of the present invention comprises the steps of: taking sandalwood oil, galangal oil, asarum oil, longan oil and borneol as active ingredients, and using the compound shown in formula (I) as an emulsifier to prepare the nanoemulsion .

In formula (I), R is a C6-C30 alkyl group containing at least one hydroxyl group; PEG represents a polyethylene glycol segment. The alkyl group may be straight-chain or branched. The present invention unexpectedly finds that the nanoemulsion with small average particle size and uniform distribution can be obtained by combining the emulsifier with the above-mentioned structure with the components of the broad chest aerosol.

In formula (I), the substituent R may be a C6-C30 alkyl group containing at least one hydroxyl group, preferably a C10-C25 alkyl group containing at least one hydroxyl group, and preferably a C13-C20 alkyl group containing at least one hydroxyl group, More preferably, it is a C16-C19 alkyl group containing at least one hydroxyl group. The number of hydroxyl groups in R is at least one, preferably 1-2. In certain embodiments, R contains two hydroxyl groups. The two hydroxyl groups can be located on different carbon atoms or on the same carbon atom. In other embodiments, R contains only one hydroxyl group. Specific examples of substituent R include, but are not limited to, 12-hydroxyoctadecyl or 15-hydroxyoctadecyl. The degree of polymerization of PEG is not particularly limited, and is, for example, 5-200, preferably 10-100. According to a preferred embodiment of the present invention, the emulsifier is polyethylene glycol-12-hydroxystearate as shown in formula (II), which has the following structural formula:

In formula (II), PEG represents a polyethylene glycol segment. Using the emulsifier mentioned above can enhance the stability of the nanoemulsion.

According to one embodiment of the present invention, the ratio α between the mass volume percent concentration of the emulsifier in % (w/v) and the volume concentration of the primary mixture in % (v/v) is 0.3 to 1.0:1; wherein , the primary mixture is composed of sandalwood oil, galangal oil, asarum oil and longan oil. α is preferably 0.35 to 0.8:1, further preferably 0.4 to 0.7, more preferably 0.5 to 0.6:1. This helps to further obtain a stable nanoemulsion.

According to the preparation method of the present invention, preferably, it comprises the following steps:

(1) Sandalwood oil, galangal oil, Asarum oil, Piper longum oil and Borneolum as active ingredient are formed into an oil phase mixture;

(2) uniformly mixing the emulsifier and the oil phase mixture to obtain the first mixture;

(3) dispersing the auxiliary material in water to obtain an aqueous phase mixture; wherein the auxiliary material includes an osmotic pressure regulator and/or a preservative;

(4) mixing the aqueous phase mixture with the first mixture to obtain a second mixture;

(5) raising the temperature of the second mixture to 40-60°C, and then cooling to 15-25°C to obtain a primary nanoemulsion;

(6) After the pH of the primary nanoemulsion is adjusted to 5.5-6.5 with a pH regulator, water is added to constant volume to obtain a nanoemulsion.

In step (1), sandalwood oil, galangal oil, asarum oil, and longan oil are firstly mixed evenly to obtain a primary mixture, and then borneol is dissolved in the primary mixture. The dissolution of borneol can be promoted by means of ultrasonic dissolution, stirring or heating. According to one embodiment of the present invention, sandalwood oil, galangal oil, asarum oil, and longan oil are uniformly mixed to obtain a primary mixture; under stirring conditions, borneol is dissolved in the primary mixture to obtain an oil phase mixture. In the nanoemulsion, the volume concentration of the primary mixture (sandalwood oil, galangal oil, asarum oil, longillinium oil) is 2-15% (v/v), more preferably 5-10% (v/v). Based on 1 ml of the total volume of sandalwood oil, galangal oil, asarum oil and longan oil, the amount of borneol used is 0.1-0.25 g, preferably 0.15-0.20 g.

In step (2), the emulsifier is uniformly mixed with the oil phase mixture to obtain a first mixture. The volume ratio of the aqueous phase mixture to the first mixture is 3-15:1, preferably 5-12:1, more preferably 7-9:1. The order of addition is not particularly limited. For example, add an emulsifier to the oil phase mixture and mix well. In the nanoemulsion, the weight volume percent concentration of the emulsifier is 1.2 to 15% (w/v), preferably 1.2 to 9% (w/v), also preferably 2 to 7% (w/v), more preferably 3 to 5% (w/v). According to a preferred embodiment of the present invention, the ratio α between the mass volume concentration of the emulsifier in % (w/v) and the volume concentration of the primary mixture in % (v/v) is 0.3 to 0.8:1, Preferably it is 0.35-0.7:1, more preferably 0.35-0.65, more preferably 0.5-0.6:1. This helps to further obtain the nanoemulsion with good stability, and improves the production stability of the nanoemulsion.

In step (3), the auxiliary material is dispersed in water to obtain a water phase mixture. The auxiliary material can be selected from one or more of osmotic pressure regulators and preservatives. The osmotic pressure regulator is selected from one or more of sodium chloride, glycerin, mannitol and glucose. The osmotic pressure regulator can adjust the osmotic pressure ratio of the nanoemulsion to 0.8-1.3, preferably 0.9-1.2, more preferably 1.0-1.1. The preservative is selected from one or more of benzalkonium chloride, benzalkonium bromide or potassium sorbate, more preferably potassium sorbate. Preservatives can inhibit the growth of bacteria in nanoemulsions. The water may be distilled water, deionized water, pure water or ultrapure water, preferably distilled water.

In step (4), the aqueous phase mixture is mixed with the first mixture to obtain a second mixture. The mixing method is not particularly limited. For example, when the aqueous phase mixture is dropped into the first mixture, the dropping rate is not particularly limited.

In step (5), the temperature of the second mixture is raised to 40-60° C., preferably 45-55° C., more preferably 48-53° C.; then the temperature is lowered. An ice bath can be used for rapid cooling. The temperature of the second mixture is lowered to 15-25°C, preferably 17-23°C, more preferably 19-21°C. The phase transition temperature method is used to balance the hydrophilic and lipophilic properties of the emulsifier to ensure the stability of the nanoemulsion.

In step (6), the pH regulator can be an aqueous solution of alkali metal hydroxide, which can be selected from aqueous solutions of NaOH or KOH. The water required for configuring the pH regulator can be distilled water. The concentration of the pH regulator is 0.1-2.5 mol/L, preferably 0.5-2 mol/L, more preferably 0.8-1.2 mol/L. The pH regulator adjusts the pH of the primary nanoemulsion to 5.5-6.5, preferably 5.7-6.3, more preferably 5.9-6.1.

In the present invention, the volume ratio of sandalwood oil, galangal oil, asarum oil and longan oil is 40～65:15～30:10～25:3～20, preferably 45～60:20～28:13～ 20:5-15, more preferably 48-55:21-25:15-18:8-12. According to a preferred embodiment of the present invention, the volume ratio of sandalwood oil, galangal oil, asarum oil and longan oil is 50:23:16:11. According to a specific embodiment of the present invention, the nanoemulsion of the present invention includes 2.5mL sandalwood oil, 1.15mL galangal oil, 0.8mL asarum oil and 0.55mL longimer oil.

According to one embodiment of the present invention, the preparation method of nanoemulsion comprises the steps:

(1) mixing sandalwood oil, galangal oil, asarum oil and longan oil evenly to obtain a primary mixture, and under stirring conditions, dissolving borneol in the primary mixture to obtain an oil phase mixture;

(2) uniformly dispersing the emulsifier in the oil phase mixture to obtain the first mixture;

(3) Uniformly dispersing the auxiliary material in water to obtain an aqueous phase mixture; the auxiliary material is selected from at least one of osmotic pressure regulators or preservatives;

(4) drop the aqueous phase mixture into the first mixture to obtain the second mixture;

(5) raising the temperature of the second mixture to 45-55° C., and cooling to 17-23° C. to obtain a primary nanoemulsion;

(6) After adjusting the pH of the primary nano-emulsion to 5.5-6.5 with 0.5-2 mol/L NaOH, adding water to constant volume to obtain the nano-emulsion.

According to a specific embodiment of the present invention, the preparation method of nanoemulsion comprises the steps:

(1) mixing sandalwood oil, galangal oil, asarum oil and longan oil evenly to obtain a primary mixture, and under stirring conditions, dissolving borneol in the primary mixture to obtain an oil phase mixture;

(2) Will HS15 is uniformly dispersed in the oil phase mixture to obtain the first mixture;

(3) Glycerin and potassium sorbate are evenly dispersed in distilled water to obtain an aqueous phase mixture;

(4) drop the aqueous phase mixture into the first mixture to obtain the second mixture;

(5) raising the temperature of the second mixture to 50°C and cooling to 20°C to obtain the primary nanoemulsion;

(6) After adjusting the pH of the primary nanoemulsion to 5.7-6.3 with 1 mol/L NaOH, add water to constant volume to obtain a nanoemulsion.

＜Nanoemulsion＞

The average particle size of the nanoemulsion of the present invention is less than 100 nm, for example, 50-85 nm. The polydispersity index PDI of the average particle diameter is less than 0.3, for example 0.05-0.2, preferably 0.05-0.15. The nanoemulsion of the present invention has excellent stability performance, and the average particle size variation range is less than 35%, preferably less than 10%, more preferably less than 5% when stored at room temperature for 45 days.

＜Preparation and use＞

The present invention also provides a pharmaceutical preparation for treating ischemic stroke, which contains the nanoemulsion of the present invention and may also contain pharmaceutically acceptable auxiliary materials. The dosage form of the pharmaceutical preparation of the present invention is not particularly limited, preferably nasal spray or nasal gel. Nanoemulsions are made into nasal sprays or in-situ gels are added to make nasal gels, which can be administered through the nasal cavity, so that the drugs can bypass the blood-brain barrier and directly reach the central nervous system, reducing the risk of non-targeted organs. Absorption, which contributes to the targeted absorption of drugs.

<test method>

The average particle size and polydispersity index (PDI) test of the nanoemulsion: the average particle size and PDI of the nanoemulsion are tested by a laser particle size analyzer.

HS15: Non-ionic surfactant produced by BASF.

In the following examples and comparative examples, the concentrations of glycerin and potassium sorbate in the nanoemulsion are 2.1 wt% and 0.1 wt% respectively; the volume ratio of the aqueous phase mixture to the first mixture is 7:1.

Example 1

(1) Mix 1.5mL sandalwood oil, 0.69mL galangal oil, 0.48mL asarum oil and 0.33mL longicorn oil to obtain a primary mixture. Under stirring conditions, dissolve 0.48g borneol in the primary mixture to obtain an oil phase mixture;

(2) Add 1.8g HS15 is uniformly dispersed in the oil phase mixture to obtain the first mixture;

(3) Glycerin and potassium sorbate are evenly dispersed in distilled water to obtain an aqueous phase mixture;

(4) drop the aqueous phase mixture into the first mixture to obtain the second mixture;

(5) raising the temperature of the second mixture to 50°C, and then cooling to 20°C to obtain a primary nanoemulsion;

(6) The pH of the primary nanoemulsion was adjusted to 6.0 with 1 mol/L NaOH, and distilled water was added to adjust the volume to 100 mL to obtain a nanoemulsion. The properties of the obtained nanoemulsion are shown in Table 1.

Example 2

(1) Mix 2.5mL sandalwood oil, 1.15mL galangal oil, 0.8mL asarum oil and 0.55mL longuminium oil evenly to obtain a primary mixture. Under stirring conditions, dissolve 0.8g borneol in the primary mixture to obtain an oil phase mixture;

(2) Add 3g HS15 is uniformly dispersed in the oil phase mixture to obtain the first mixture;

(3) Glycerin and potassium sorbate are evenly dispersed in distilled water to obtain an aqueous phase mixture;

(4) drop the aqueous phase mixture into the first mixture to obtain the second mixture;

(5) raising the temperature of the second mixture to 50°C, and then cooling to 20°C to obtain a primary nanoemulsion;

(6) The pH of the primary nanoemulsion was adjusted to 6.0 with 1 mol/L NaOH, and distilled water was added to adjust the volume to 100 mL to obtain a nanoemulsion. The performance of gained nanoemulsion is referring to Fig. 1, Fig. 2, table 1.

Example 3

(1) Mix 5mL sandalwood oil, 2.3mL galangal oil, 1.6mL asarum oil and 1.1mL longan oil evenly to obtain a primary mixture. Under stirring conditions, dissolve 1.6g borneol in the primary mixture to obtain an oil phase mixture ;

(2) Add 6g HS15 is uniformly dispersed in the oil phase mixture to obtain the first mixture;

(3) Glycerin and potassium sorbate are evenly dispersed in distilled water to obtain an aqueous phase mixture;

(4) drop the aqueous phase mixture into the first mixture to obtain the second mixture;

(5) raising the temperature of the second mixture to 50°C, and then cooling to 20°C to obtain a primary nanoemulsion;

(6) The pH of the primary nanoemulsion was adjusted to 6.0 with 1 mol/L NaOH, and distilled water was added to adjust the volume to 100 mL to obtain a nanoemulsion. The properties of the obtained nanoemulsion are shown in Table 1.

Example 4

(1) Mix 7.5mL sandalwood oil, 3.45mL galangal oil, 2.4mL asarum oil and 1.65mL longuminium oil to obtain a primary mixture. Under stirring conditions, dissolve 2.4g borneol in the primary mixture to obtain an oil phase mixture;

(2) Add 9g HS15 is uniformly dispersed in the oil phase mixture to obtain the first mixture;

(3) Glycerin and potassium sorbate are evenly dispersed in distilled water to obtain an aqueous phase mixture;

(4) drop the aqueous phase mixture into the first mixture to obtain the second mixture;

(5) raising the temperature of the second mixture to 50°C and cooling to 20°C to obtain the primary nanoemulsion;

(6) The pH of the primary nanoemulsion was adjusted to 6.0 with 1 mol/L NaOH, and distilled water was added to adjust the volume to 100 mL to obtain a nanoemulsion. The properties of the obtained nanoemulsion are shown in Table 1.

Table 1

Note: α1 means in % (w/v) The ratio between the mass volume percent concentration of HS15 and the primary mixture volume concentration in % (v/v).

As can be seen from Table 1, when expressed in % (w/v) When the ratio α1 between the HS15 mass volume percent concentration and the volume concentration of the primary mixture in % (v/v) is 0.6, changing the concentration of the primary mixture and emulsifier has no effect on the average particle diameter and polydispersity index of the nanoemulsion big.

Example 5

Will in embodiment 2 The amount of HS15 was changed to 3.5g, and all the other conditions were the same as in Example 1. The properties of the resulting nanoemulsion are shown in Figure 1.

Example 6

Will in embodiment 2 The amount of HS15 was changed to 4g, and all the other conditions were the same as in Example 1. The properties of the obtained nanoemulsion are shown in Fig. 1 and Fig. 2 .

Example 7

Will in embodiment 2 The amount of HS15 was changed to 4.5g, and all the other conditions were the same as in Example 1. The properties of the resulting nanoemulsion are shown in Figure 1.

Example 8

Will in embodiment 2 The amount of HS15 was changed to 5g, and all the other conditions were the same as in Example 1. The performance of gained nanoemulsion is referring to Fig. 1, Fig. 2, table 2.

Comparative Example 1

Except the 5g in embodiment 5 Except that HS15 was replaced with 5 g of polyethylene glycol 1000 vitamin E succinate (TPGS), the rest of the conditions were the same as in Example 5. The performance of the obtained nanoemulsion is shown in Table 2.

Comparative Example 2

Except the 5g in embodiment 5 Except that HS15 was replaced with 5 g of block polyether F-68 (Pluronic F68), the rest of the conditions were the same as in Example 5. The performance of the obtained nanoemulsion is shown in Table 2.

Table 2

As can be seen from Table 2, compared with TPGS and Pluronic F68, using The average particle size of the nanoemulsion formed by HS15 is small and the distribution is uniform.

As can be seen from Fig. 1, in embodiment 1 and embodiment 5～8, along with in the nanoemulsion The average particle size and polydispersity index of the nanoemulsion decreased gradually with the increasing of HS15 concentration.

It can be seen from Figure 2 that in the nanoemulsion The HS15 concentration of 3% (w/v) has the best stability of the formed nanoemulsion compared to the concentrations of 4% (w/v) and 5% (w/v).

The present invention is not limited to the above-mentioned embodiments. Without departing from the essence of the present invention, any deformation, improvement, and replacement conceivable by those skilled in the art fall within the scope of the present invention.

Claims (10)

1. a preparation method of nanoemulsion, is characterized in that, comprises the steps: take sandalwood oil, galangal oil, Asarum oil, Piper longum oil and Borneolum as active ingredient, take the compound shown in formula (I) as emulsification agent to prepare a nanoemulsion, In formula (I), R is a C6-C30 alkyl group containing at least one hydroxyl group, and PEG represents a polyethylene glycol segment. 2. The preparation method according to claim 1, characterized in that, in formula (I), R is a C10-C25 alkyl group containing at least one hydroxyl group. 3. preparation method according to claim 2, is characterized in that, described emulsifying agent is polyethylene glycol-12-hydroxystearate, and its structure is as shown in formula (II), Wherein, PEG represents a polyethylene glycol segment. 4. according to the preparation method described in any one of claim 1～3, it is characterized in that, the emulsifier mass volume percentage concentration in % (w/v) and the primary mixture volume concentration in % (v/v) The ratio α between them is 0.3～1.0:1; Wherein, the primary mixture is composed of sandalwood oil, galangal oil, asarum oil and longillinium oil. 5. The preparation method according to any one of claims 1 to 3, characterized in that it comprises the steps of: (1) Sandalwood oil, galangal oil, Asarum oil, Piper longum oil and Borneolum as active ingredient are formed into an oil phase mixture; (2) uniformly mixing the emulsifier and the oil phase mixture to obtain the first mixture; (3) dispersing the auxiliary material in water to obtain an aqueous phase mixture; wherein, the auxiliary material includes an osmotic pressure regulator and/or a preservative; (4) mixing the aqueous phase mixture with the first mixture to obtain a second mixture; (5) raising the temperature of the second mixture to 40-60°C, and then cooling down to 15-25°C to obtain a primary nanoemulsion; (6) After the pH of the primary nanoemulsion is adjusted to 5.5-6.5 with a pH regulator, water is added to constant volume to obtain the nanoemulsion. 6. preparation method according to claim 5 is characterized in that, in step (2), the emulsifier mass volume percentage concentration in % (w/v) and the primary mixture volume in % (v/v) The ratio α between the concentrations is 0.3-1.0:1; wherein, the primary mixture is composed of sandalwood oil, galangal oil, asarum oil and longillinium oil. 7. The preparation method according to claim 6, characterized in that, in the nanoemulsion, the mass volume percent concentration of the emulsifier is 1.2 to 15% (w/v), and the volume concentration of the primary mixture is 2 to 15%. %(v/v). 8. the preparation method according to claim 6 is characterized in that, the volume ratio of sandalwood oil, galangal oil, Asarum oil and Piper longum oil is 40～65:15～30:10～25:3～20; Based on 1 ml of the total volume of sandalwood oil, galangal oil, asarum oil and longan oil, the dosage of the borneol is 0.1-0.25 g. 9. A nanoemulsion, characterized in that it is obtained by the preparation method according to any one of claims 1 to 8, the average particle diameter of the nanoemulsion is less than 100 nm, and the polydispersity index PDI is less than 0.3. 10. use of the nanoemulsion according to claim 9 in the preparation of a medicament for the treatment of ischemic stroke.