阅读说明：本技术 罗布麻黄酮自微乳方法及其应用 (Apocynum venetum flavone self-microemulsion method and application thereof ) 是由 高钢 朱爱国 陈继康 喻春明 陈平 陈坤梅 王晓飞 于 2021-09-16 设计创作，主要内容包括：本发明涉及药物制剂技术领域,尤其涉及罗布麻黄酮自微乳及其应用。本发明是将罗布麻黄酮与乳化助剂和溶剂共同制成自微乳制剂,其中溶剂为乙醇和/或罗布麻全谱系精油。纳米微乳滴粒径约8～24nm。罗布麻黄酮在水中的溶解度可以提高到20～35mg/mL,罗布麻全谱系精制油提高到1％～10％。相较于已有的水溶性罗布麻黄酮粉末制剂,本发明使罗布麻黄酮的溶解度进一步提高,生物利用度提高2～10倍。本发明制备的自微乳工艺简单,便于操作,且本发明热力学稳定性好,贮存稳定性良好,久置不分层,离心加速试验中,12000rpm离心20min不分层。(The invention relates to the technical field of pharmaceutical preparations, in particular to apocynum venetum flavone self-microemulsion and application thereof. The invention relates to a self-microemulsion preparation prepared by apocynum flavone, an emulsification aid and a solvent, wherein the solvent is ethanol and/or apocynum full spectrum essential oil. The particle size of the nano microemulsion drops is about 8-24 nm. The solubility of the apocynum venetum flavone in water can be improved to 20-35 mg/mL, and the solubility of the apocynum venetum total spectrum refined oil is improved to 1% -10%. Compared with the existing water-soluble apocynum venetum flavone powder preparation, the preparation method disclosed by the invention has the advantages that the solubility of apocynum venetum flavone is further improved, and the bioavailability is improved by 2-10 times. The self-microemulsion prepared by the invention has simple process and convenient operation, and the invention has good thermodynamic stability and storage stability, can not be layered after being placed for a long time, and can not be layered after being centrifuged at 12000rpm for 20min in a centrifugation acceleration test.)

1. The apocynum venetum flavone self-microemulsion is characterized by being prepared from apocynum venetum flavone, a solvent, water and an emulsification aid; wherein, the mass fraction of the apocynum venetum flavone is 0.5 to 5 percent;

the solvent is at least one of ethanol or apocynum venetum full spectrum essential oil;

the emulsifying aid is at least one of glycerol, polypropylene glycol-13-decyl tetradecanol polyether-24 or polyethylene glycol/polypropylene glycol/polytetramethylene glycol-8/5/3.

2. The apocynum venetum flavone self-microemulsion according to claim 1, characterized in that,

is prepared from herba Apocyni Veneti flavone, glycerol, ethanol, water, polypropylene glycol-13-decyl tetradecanol polyether-24 and polyethylene glycol/polypropylene glycol/polybutylene glycol-8/5/3;

or herba Apocyni Veneti flavone, herba Apocyni Veneti full spectrum essential oil, ethanol, water, polypropylene glycol-13-decyltetradecanol polyether-24 and polyethylene glycol/polypropylene glycol/polybutylene glycol-8/5/3.

3. A method for preparing apocynum venetum flavone self-microemulsion according to claim 1 or 2, characterized by comprising:

step 1: dissolving the apocynum venetum ketone in a solvent to prepare a flavone solution with the mass fraction of 12.5-50%;

step 2: mixing the flavone solution with an emulsifying aid and then stirring;

and step 3: adding water and continuously stirring to obtain the apocynum venetum self-microemulsion.

4. The preparation method according to claim 3, wherein the mass-volume ratio of the emulsification aid to the flavone solution is (8.5 g-10.64 g): (1 mL-3.75 mL).

5. The method according to claim 3, wherein the stirring in step 2 is carried out at a temperature of 60 to 65 ℃ and at a speed of 700 to 900rpm for 2 min.

6. The preparation method according to claim 3, wherein the stirring in step 3 comprises stirring at a temperature of 60-65 ℃ and at a speed of 700-900 rpm for 2 min; then naturally cooling and continuously stirring for 2min at 400-500 rpm.

7. The method according to claim 3, wherein the water is added in step 3 in a volume such that the volume fraction of water is less than 10%.

8. Apocynum venetum flavone self-microemulsion prepared by the preparation method of any one of claims 3 to 7.

9. Use of apocynum venetum flavone self-microemulsion according to claim 1 or 2 or apocynum venetum flavone self-microemulsion prepared by the preparation method according to any one of claims 3 to 7 in preparation of foods, medicines and/or cosmetics.

10. Food, medicine and/or cosmetic containing the apocynum venetum flavone self-microemulsion according to claim 1 or 2 or the apocynum venetum flavone self-microemulsion prepared by the preparation method according to any one of claims 3 to 7.

Technical Field

The invention relates to the technical field of pharmaceutical preparations, in particular to apocynum venetum flavone self-microemulsion and application thereof.

Background

Flavonoid compounds (flavanones) are valuable active ingredients of apocynum venetum extract species, have a ketone carbonyl group in the molecule, have basicity of the first oxygen atom, can form a salt with strong acid, and have yellow hydroxyl derivatives, so the flavonoid compounds are also called as flavonones or flavones. Pharmacological experiments show that the apocynum venetum has better curative effects on preventing and treating hypertension and hyperlipidemia and has good effects on treating multiple sclerosis. Meanwhile, the tea has a series of physiological activity functions of resisting bacteria, resisting insomnia and the like. The flavone also has antioxidant effect, and has effect superior to ascorbate or vitamin E, and is a potential antioxidant. Therefore, the flavone has extremely wide biomedical application prospect.

Due to the complex metabolic network of organisms, it is often difficult for elemental chemicals to achieve a comprehensive physiological function regulating effect, and thus complex formulation regulation is often required. Apocynum venetum is a perennial herb bast fiber plant and a medicinal resource plant which are worth paying attention to in China. In recent years, health care fabrics of apocynum venetum are favored, and the chemical components and pharmacological research thereof are also extremely active. The apocynum venetum plant contains apocynum venetum flavone (> 70%) and other volatile substances. The volatile substances can also achieve the effects of similar antibiosis, anti-inflammation and the like at certain concentration. Compared with pure apocynum venetum flavone, the apocynum venetum essential oil which is low in price and rich in volatile substances is more popular in the fields of daily use and cosmetics. However, neither pure apocynum flavone nor apocynum extract oil are easily soluble in water, and in order to improve their bioavailability, formulation or process improvements are often required to increase their water solubility to achieve maximum availability.

In recent years, the research on apocynum venetum flavone at home and abroad mainly focuses on the extraction process, content measurement and pharmacological activity of the apocynum venetum flavone, but the research on the preparation of the apocynum venetum flavone or apocynum venetum full spectrum refined oil is less, only water-soluble apocynum venetum flavone powder exists, and the research and application of the emulsion related to the apocynum venetum flavone or apocynum venetum full spectrum refined oil does not appear.

Disclosure of Invention

In view of the above, the technical problem to be solved by the present invention is to provide apocynum venetum flavone self-microemulsion and applications thereof, wherein the self-microemulsion has a small average particle size, a high drug loading amount, a high solubility, and good long-term stability.

The invention provides apocynum venetum flavone self-microemulsion which is prepared from apocynum venetum flavone, a solvent, water and an emulsification aid; wherein, the mass fraction of the apocynum venetum flavone is 0.5 to 5 percent;

the solvent is at least one of ethanol or apocynum venetum full spectrum essential oil;

the emulsifying aid is at least one of glycerol, polypropylene glycol-13-decyl tetradecanol polyether-24 or polyethylene glycol/polypropylene glycol/polytetramethylene glycol-8/5/3.

In the invention, the apocynum venetum flavone self-microemulsion is prepared from apocynum venetum flavone, glycerol, ethanol, water, polypropylene glycol-13-decyl tetradecyl alcohol polyether-24 and polyethylene glycol/polypropylene glycol/polybutylene glycol-8/5/3;

or herba Apocyni Veneti flavone, herba Apocyni Veneti full spectrum essential oil, ethanol, water, polypropylene glycol-13-decyltetradecanol polyether-24 and polyethylene glycol/polypropylene glycol/polybutylene glycol-8/5/3.

In some embodiments, the apocynum flavone self-microemulsion is prepared from 0.5 parts by mass of apocynum flavone, 0.64 parts by mass of glycerin, ethanol, water, 5 parts by mass of polypropylene glycol-13-decyltetradecanol polyether-24, and 5 parts by mass of polyethylene glycol/polypropylene glycol/polybutylene glycol-8/5/3; wherein the mass-volume ratio of the apocynum venetum flavone to the ethanol is 0.5 g: 1mL, the volume of water does not exceed 1/10 parts of ethanol.

In some embodiments, the apocynum flavone self-microemulsion is prepared from 0.4 parts by mass of apocynum flavone, 0.8 parts by mass of glycerol, ethanol, water, 4.5 parts by mass of polypropylene glycol-13-decyltetradecanol polyether-24 and 4.5 parts by mass of polyethylene glycol/polypropylene glycol/polybutylene glycol-8/5/3; wherein the mass-volume ratio of the apocynum venetum flavone to the ethanol is 0.4 g: 1mL, the volume of water does not exceed 1/10 parts of ethanol.

In some embodiments, the apocynum flavone self-microemulsion is prepared from 0.4 parts by mass of apocynum flavone, 0.5 parts by mass of glycerol, ethanol, water, 4.5 parts by mass of polypropylene glycol-13-decyltetradecanol polyether-24 and 4.5 parts by mass of polyethylene glycol/polypropylene glycol/polybutylene glycol-8/5/3; wherein the mass-volume ratio of the apocynum venetum flavone to the ethanol is 0.4 g: 1mL, the volume of water does not exceed 1/10 parts of ethanol.

In some embodiments, the apocynum venetum flavone self-microemulsion is prepared from 1.25 parts by mass of apocynum venetum flavone, 1.25 parts by mass of apocynum venetum full spectrum essential oil, ethanol, water, 4 parts by mass of polypropylene glycol-13-decyltetradecanol polyether-24 and 5 parts by mass of polyethylene glycol/polypropylene glycol/polybutylene glycol-8/5/3; wherein the mass-volume ratio of the apocynum venetum flavone to the ethanol is 1.25 g: 2.5mL, the volume of water does not exceed 1/25 parts of ethanol.

In some embodiments, the apocynum venetum flavone self-microemulsion is prepared from 1.65 parts by mass of apocynum venetum flavone, 1.65 parts by mass of apocynum venetum full spectrum essential oil, ethanol, water, 5 parts by mass of polypropylene glycol-13-decyltetradecanol polyether-24 and 5 parts by mass of polyethylene glycol/polypropylene glycol/polybutylene glycol-8/5/3; wherein the mass-volume ratio of the apocynum venetum flavone to the ethanol is 1.65 g: 1.7mL, the volume of water does not exceed 1/17 for ethanol.

In some embodiments, the apocynum venetum flavone self-microemulsion is prepared from 2.3 parts by mass of apocynum venetum flavone, 2.3 parts by mass of apocynum venetum full spectrum essential oil, ethanol, water, 5 parts by mass of polypropylene glycol-13-decyltetradecanol polyether-24 and 5 parts by mass of polyethylene glycol/polypropylene glycol/polybutylene glycol-8/5/3; wherein the mass-volume ratio of the apocynum venetum flavone to the ethanol is 2.3 g: 0.4mL, the volume of water does not exceed 1/4 for ethanol.

The invention also provides a preparation method of the apocynum venetum flavone self-microemulsion, which comprises the following steps:

step 1: dissolving the apocynum venetum ketone in a solvent to prepare a flavone solution with the mass fraction of 12.5-50%;

step 2: mixing the flavone solution with an emulsifying aid and then stirring;

and step 3: adding water and continuously stirring to obtain the apocynum venetum self-microemulsion.

In the invention, the mass-volume ratio of the emulsification aid to the flavone solution is (8.5 g-10.64 g): (1 mL-3.75 mL).

And 2, stirring for 2min under the conditions of 60-65 ℃ and 700-900 rpm.

Stirring for 2min at the temperature of 60-65 ℃ and at the rpm of 700-900 in the step 3; then naturally cooling and continuously stirring for 2min at 400-500 rpm.

And (3) adding water in the step until the volume fraction of the water is less than 10%.

The apocynum venetum flavone self-microemulsion prepared by the preparation method is provided.

The self-microemulsion provided by the invention can be diluted into apocynum flavone or apocynum full-spectrum refined oil nano-microemulsion with different concentrations for external use according to requirements in practical application. The system is very thick when the dilution is started, and transparent gel liquid can appear after the ultrapure water is continuously dripped and continuously stirred. After being placed for a few minutes at low temperature, the system becomes uniform and transparent, namely the oil-in-water nano microemulsion. The nano microemulsion of apocynum venetum flavone or full spectrum refined oil is clear, transparent and light yellow.

The apocynum venetum flavone self-microemulsion or the apocynum venetum flavone self-microemulsion prepared by the preparation method disclosed by the invention is applied to preparation of foods, medicines and/or cosmetics.

The apocynum venetum flavone self-microemulsion or the apocynum venetum flavone self-microemulsion prepared by the preparation method is used for preparing foods, medicines and/or cosmetics.

The invention relates to a self-microemulsion preparation prepared by apocynum flavone, an emulsification aid and a solvent, wherein the solvent is ethanol and/or apocynum full spectrum essential oil. The particle size of the nano microemulsion drops is about 8-24 nm. The solubility of the apocynum venetum flavone in water can be improved to 20-35 mg/mL, and the solubility of the apocynum venetum total spectrum refined oil is improved to 1-10%. Compared with the existing water-soluble apocynum venetum flavone powder preparation, the preparation method disclosed by the invention has the advantages that the solubility of apocynum venetum flavone is further improved, and the bioavailability is improved by 2-10 times. The self-microemulsion prepared by the invention has simple process and convenient operation, and the invention has good thermodynamic stability and storage stability, can not be layered after being placed for a long time, and can not be layered after being centrifuged at 12000rpm for 20min in a centrifugation acceleration test.

Drawings

FIG. 1 is the particle size distribution diagram of the microemulsion of apocynin prepared in example 3;

FIG. 2 is a micrograph of microemulsion of apocynin prepared in example 3;

FIG. 3 is the particle size distribution diagram of the microemulsion of apocynin obtained in example 6;

fig. 4 is a micrograph of microemulsion of apocynum venetum flavone prepared in example 3.

Detailed Description

The invention provides apocynum venetum flavone self-microemulsion and application thereof, and a person skilled in the art can realize the self-microemulsion by properly improving process parameters by referring to the content. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.

The test materials adopted by the invention are all common commercial products and can be purchased in the market.

The preparation method of the apocynum venetum full spectrum essential oil comprises the following steps:

1. in the blooming period of apocynum venetum, inflorescences are stroked first, and then the whole plant is harvested. The fresh flower infruction directly enters the essential oil extraction stage. And (3) drying the harvested other materials in the sun, beating or rolling until the leaves fall off when more than 50% of the leaves are dry-rolled, so as to realize the separation of the leaves and the stalks. The leaf is collected and enters the essential oil extraction stage.

2. The extraction method comprises the following steps: fresh flowers or dry leaves are respectively stirred and soaked in deionized water for 1-1.5 hours to prepare raw material samples, and the solid-liquid mass ratio is 1: 6-8. Adding the raw material sample into a distillation device, and heating and distilling at 95-100 ℃ for 3.5-4 hours to obtain a distillate. When the distillate is clear and transparent and does not contain organic substances like oil beads, the distillation is stopped, and the essential oil is collected.

3. Extracting essential oil from flowers and leaves respectively, and mixing according to the proportion of 1: 5-7 to obtain the full spectrum essential oil.

The preparation method of the apocynum venetum flavone comprises the following steps:

crushing a proper amount of dry leaves of apocynum venetum, sieving the crushed dry leaves, performing ultrasonic extraction on the crushed dry leaves with 80 percent ethanol for three times, combining extracting solutions, filtering, concentrating the filtrate under reduced pressure to be dry, performing ultrasonic dissolution with absolute ethanol, filtering, concentrating the filtrate under reduced pressure to be the minimum volume, preparing a liquid phase (Waters2555) after filtering with a microporous membrane, preparing a chromatographic column with GLP-ID100mm multiplied by 450mm, and preparing conditions: and the acetonitrile gradient is 10-90% of acetonitrile, the fraction with flavone characteristics with a spectral band I of 270nm and a spectral band II of 350nm is collected for 0-60 min, the total flavone is collected, and the apocynum venetum total flavone powder is obtained through reduced pressure concentration. Analytical liquid phase (Waters acidity) column was nano-micro, 3 μm, 4.6 × 150 mm; analysis conditions were as follows: scanning at full wavelength; gradient of acetonitrile: acetonitrile: 0.2 percent of acetic acid water, 0 to 60min and 10 to 90 percent of acetonitrile.

The invention is further illustrated by the following examples:

example 1:

a method for preparing apocynum venetum flavone self-microemulsion comprises the following steps:

(1) weighing 0.5g of apocynum venetum flavone, 5g of PPG-13-decyltetradecanol polyether-24 and 5g of PEG/PPG/polytetramethylene glycol-8/5/3 as medicinal components for later use;

(2) dissolving the apocynum venetum flavone solid powder in the step (1) in 1mL of ethanol to prepare 50% apocynum venetum ketone ethanol solution;

(3) adding 0.64g of glycerol, 5g of PPG-13-decyltetradecanol polyether-24 and 5g of PEG/PPG/polytetramethylene glycol-8/5/3 into the mixture obtained in the step (2), and uniformly stirring the mixture at 65 ℃ and 700-900 rpm until a small amount of bubbles appear in the solution, thus obtaining a clear and transparent apocynum venetum flavone oily self-microemulsion;

(4) slowly dripping ultrapure water with a micro volume (less than 100 mu L) into the mixture obtained in the step (3), and uniformly stirring at 65 ℃ and 700-900 rpm;

(5) and (4) stirring the mixture in the step (4) at 400-500 rpm under a natural cooling condition until the mixture is clear and bright, so as to obtain a microemulsion concentrated solution of pure apocynum venetum flavone, wherein the appearance of the microemulsion concentrated solution is clear and bright colorless oily liquid.

Example 2:

a method for preparing apocynum venetum flavone self-microemulsion comprises the following steps:

(1) weighing 0.4g of apocynum venetum flavone, 4.5g of PPG-13-decyltetradecanol polyether-24 and 4.5g of PEG/PPG/polytetramethylene glycol-8/5/3 for later use;

(2) dissolving the apocynum venetum flavone solid powder in the step (1) in 1mL of ethanol to prepare 40% apocynum venetum ketone ethanol solution;

(3) adding 0.8g of glycerol, 4.5g of PPG-13-decyltetradecanol polyether-24 and 4.5g of PEG/PPG/polytetramethylene glycol-8/5/3 into the mixture obtained in the step (2), and uniformly stirring the mixture at the temperature of 65 ℃ and the rpm of 700-900 until a small amount of bubbles appear in the solution, thereby obtaining the clear and transparent apocynum venetum flavone oily self-microemulsion;

(4) slowly dripping ultrapure water with a micro volume (less than 100 mu L) into the mixture obtained in the step (3), and uniformly stirring at 65 ℃ and 700-900 rpm;

(5) and (4) stirring the mixture in the step (4) at 400-500 rpm under a natural cooling condition until the mixture is clear and bright, so as to obtain a microemulsion concentrated solution of pure apocynum venetum flavone, wherein the appearance of the microemulsion concentrated solution is clear and bright colorless oily liquid.

Example 3:

a method for preparing apocynum venetum flavone self-microemulsion comprises the following steps:

(1) weighing 0.4g of apocynum venetum flavone, 4.0g of PPG-13-decyltetradecanol polyether-24 and 4.0g of PEG/PPG/polytetramethylene glycol-8/5/3 for later use;

(2) dissolving the apocynum venetum flavone solid powder in the step (1) in 1mL of ethanol to prepare 40% apocynum venetum ketone ethanol solution;

(3) adding 0.5g of glycerol, 4.0g of PPG-13-decyltetradecanol polyether-24 and 4.0g of PEG/PPG/polytetramethylene glycol-8/5/3 into the mixture obtained in the step (2), and uniformly stirring the mixture at the temperature of 65 ℃ and the rpm of 700-900 until a small amount of bubbles appear in the solution, thereby obtaining the clear and transparent apocynum venetum flavone oily self-microemulsion;

(4) slowly dripping ultrapure water with a micro volume (less than 100 mu L) into the mixture obtained in the step (3), and uniformly stirring at 65 ℃ and 700-900 rpm;

(5) and (4) stirring the mixture in the step (4) at 400-500 rpm under a natural cooling condition until the mixture is clear and bright, so as to obtain a microemulsion concentrated solution of pure apocynum venetum flavone, wherein the appearance of the microemulsion concentrated solution is clear and bright colorless oily liquid.

Example 4:

a method for preparing apocynum venetum full-spectrum refined oil self-microemulsion comprises the following steps:

(1) weighing 2.5g of apocynum venetum full spectrum refined oil (1.25 parts by mass of apocynum venetum flavone and 1.25 parts by mass of apocynum venetum full spectrum essential oil), 5g of PPG-13-decyltetradecanol polyether-24 and 5g of PEG/PPG/polytetramethylene glycol-8/5/3 for later use;

(2) dissolving (1) with ethanol to obtain 25% refined oil (12.5% flavone) of herba Apocyni Veneti whole spectrum;

(3) adding 5g of PPG-13-decyltetradecanol polyether-24 and 5g of PEG/PPG/polytetramethylene glycol-8/5/3 into the mixture obtained in the step (2), and uniformly stirring at 60 ℃ and 700-900 rpm until the solvent emits a trace of bubbles;

(4) slowly dripping ultrapure water with a micro volume (less than 100 mu L) into the mixture obtained in the step (3), and stirring the mixture at the temperature of 60 ℃ and the rpm of 700-900 to be uniform;

(5) and (4) stirring the mixture in the step (4) at 400-500 rpm under a natural cooling condition until the mixture is clear and bright, so as to obtain a microemulsion concentrated solution of the apocynum venetum full spectrum refined oil, wherein the appearance of the microemulsion concentrated solution is a clear and bright light yellow oily liquid.

Example 5:

a method for preparing apocynum venetum full-spectrum refined oil self-microemulsion comprises the following steps:

(1) weighing 3.3g of apocynum venetum full spectrum refined oil (1.65 parts by mass of apocynum venetum flavone and 1.65 parts by mass of apocynum venetum full spectrum essential oil), 5g of PPG-13-decyltetradecanol polyether-24 and 5g of PEG/PPG/polytetramethylene glycol-8/5/3 for later use;

(2) dissolving (1) with ethanol to obtain 66% refined oil (33% flavone) of Apocynum venetum;

(3) adding 5g of PPG-13-decyltetradecanol polyether-24 and 5g of PEG/PPG/polytetramethylene glycol-8/5/3 into the mixture obtained in the step (2), and uniformly stirring at 60 ℃ and 700-900 rpm until the solvent emits a trace of bubbles;

(4) slowly dripping ultrapure water with a micro volume (less than 100 mu L) into the mixture obtained in the step (3), and stirring the mixture at the temperature of 60 ℃ and the rpm of 700-900 to be uniform;

(5) and (4) stirring the mixture in the step (4) at 400-500 rpm under a natural cooling condition until the mixture is clear and bright, so as to obtain a microemulsion concentrated solution of the apocynum venetum full spectrum refined oil, wherein the appearance of the microemulsion concentrated solution is a clear and bright light yellow oily liquid.

Example 6:

a method for preparing apocynum venetum full-spectrum refined oil self-microemulsion comprises the following steps:

(1) weighing 4.6g of apocynum venetum full spectrum refined oil (2.3 parts by mass of apocynum venetum flavone and 2.3 parts by mass of apocynum venetum full spectrum essential oil, 4g of PPG-13-decyltetradecanol polyether-24 and 5g of PEG/PPG/polytetramethylene glycol-8/5/3 for later use;

(2) dissolving (1) with ethanol to obtain 92% refined oil (46% flavone) of Apocynum venetum;

(3) adding 4g of PPG-13-decyltetradecanol polyether-24 and 5g of PEG/PPG/polytetramethylene glycol-8/5/3 into the mixture obtained in the step (2), and uniformly stirring at 60 ℃ and 700-900 rpm until the solvent emits a trace of bubbles;

(4) slowly dripping ultrapure water with a micro volume (less than 100 mu L) into the mixture obtained in the step (3), and stirring the mixture at the temperature of 60 ℃ and the rpm of 700-900 to be uniform;

(5) and (4) stirring the mixture in the step (4) at 400-500 rpm under a natural cooling condition until the mixture is clear and bright, so as to obtain a microemulsion concentrated solution of the apocynum venetum full spectrum refined oil, wherein the appearance of the microemulsion concentrated solution is a clear and bright light yellow oily liquid.

Effect detection

1. Appearance, particle size, and solubility (drug loading) measurements:

in examples 1-3, example 3 is the best process, the drug loading (total solubility in solvent) of pure apocynum venetum flavone is the highest and reaches 35.6mg/ml, and the drug loading is remarkably superior to that of example 1 or example 2. The microemulsion is colorless and transparent in appearance and stable after long-term storage no matter high-power or low-power dilution. And the particle size of the nano-emulsion obtained after dilution is relatively small, as shown in figures 1 and 2, the average particle size of the nano-microemulsion is about 24nm and is higher than that of the nano-microemulsion in example 1 (the average particle size of the microemulsion is 15nm) and that of the nano-microemulsion in example 2 (the average particle size of the microemulsion is 18 nm). The self-microemulsion prepared in the three examples has no obvious change in appearance and is stable after being stored for a long time.

In examples 4 to 6, example 6 is the best process, and the drug loading (total solubility in solvent) of the apocynum venetum full spectrum refined oil is the highest and reaches 10%, which is significantly better than that of example 1 or example 2. The microemulsion is light yellow transparent no matter high-power or low-power dilution, and is stable after long-time storage. And the particle size of the nano-emulsion obtained after dilution is relatively small, as shown in fig. 3 and 4, the average particle size of the nano-microemulsion is about 8 nm. The self-microemulsion prepared in the three examples has no obvious change in appearance and is stable after being stored for a long time.

2. Stability of

The self-microemulsion prepared in the embodiments 1 to 6 has simple process, convenient operation, good thermodynamic stability and good storage stability, and the self-microemulsion of the embodiments 1 to 6 is placed in an incubator at 28 ℃ for 1 to 2 months, so that the self-microemulsion is not layered after being placed for a long time and has no particle aggregation phenomenon;

centrifugal acceleration test detection shows that under the condition of centrifugation at 12000rpm for 20min, the self-microemulsions in examples 1-6 have no layering phenomenon, and are good in stability.

3. Solubility or bioavailability. The self-microemulsion of the embodiments 1 to 3 can improve the solubility of the apocynin powder in water (total solvent) to 20 to 35 mg/mL; the self-microemulsion of the embodiments 4 to 6 can improve the solubility of the apocynum venetum full spectrum refined oil in water (total solvent) to 1 to 10 percent. Compared with the existing water-soluble apocynum venetum flavone powder preparation, the self-microemulsion of the embodiments 1 to 6 further improves the solubility of apocynum venetum flavone and improves the bioavailability by 2 to 10 times. The self-microemulsion of the embodiment 3 has the highest bioavailability which is 10 times of that of the apocynum venetum powder preparation in the prior art.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that it is obvious to those skilled in the art that various modifications and improvements can be made without departing from the principle of the present invention, and these modifications and improvements should also be considered as the protection scope of the present invention.