CN112007013A

CN112007013A - Artemisia argyi flavone microcapsule and preparation method and application thereof

Info

Publication number: CN112007013A
Application number: CN202010766820.7A
Authority: CN
Inventors: 李�杰; 孟祥龙; 王春艳; 马艳莉; 杜朝军; 李翠翠; 李斌; 周永康
Original assignee: Nanyang Institute of Technology
Current assignee: Nanyang Institute of Technology
Priority date: 2020-08-03
Filing date: 2020-08-03
Publication date: 2020-12-01

Abstract

The invention is suitable for the technical field of microcapsules, and provides a wormwood flavone microcapsule and a preparation method and application thereof, wherein the wormwood flavone microcapsule comprises: core material, which is wormwood flavone; and the wall material comprises maltodextrin and auxiliary materials, and the mass ratio of the wall material to the core material is (6-12) to 1; the mass ratio of the maltodextrin to the auxiliary materials is (0.8-1.6): 1; the auxiliary material is at least one of soybean protein isolate, whey protein, carboxymethyl cellulose, Arabic gum, xanthan gum, carrageenan and gelatin. According to the invention, the ratio of the core material to the wall material, the ratio of the maltodextrin to the auxiliary material and the like are optimized, so that the embedding rate of the wormwood flavone microcapsules can be obviously improved, and the quality and the medicinal value of the wormwood flavone microcapsules can be improved.

Description

Artemisia argyi flavone microcapsule and preparation method and application thereof

Technical Field

The invention belongs to the technical field of microcapsules, and particularly relates to a wormwood flavone microcapsule as well as a preparation method and application thereof.

Background

Folium Artemisiae Argyi has effects of warming channels, eliminating dampness, dispelling cold, stopping bleeding, diminishing inflammation, relieving asthma, relieving cough, preventing miscarriage, and resisting allergy. Wherein, the flavonoids compounds such as rutin in the wormwood have the functions of resisting free radicals, resisting oxidation, inhibiting bacteria, improving immunity and the like, and have higher medicinal value. However, the prior art reports that flavonoids in wormwood are used for medicine.

In addition, a microcapsule refers to a micro-container or package with a polymer or inorganic wall, which is commonly used as a carrier for drugs. However, the existing flavone microcapsules have the problems of low embedding rate and the like. Therefore, at present, there is a need to research a wormwood flavone microcapsule with a high embedding rate so as to reasonably utilize flavonoids in wormwood.

Disclosure of Invention

The embodiment of the invention aims to provide a wormwood flavone microcapsule, aiming at solving the problems in the background art.

The embodiment of the invention is realized by that the wormwood flavone microcapsule comprises:

core material, which is wormwood flavone; and

the wall material comprises maltodextrin and auxiliary materials, and the mass ratio of the wall material to the core material is (6-12): 1; the mass ratio of the maltodextrin to the auxiliary materials is 1 (0.8-1.6); the auxiliary material is at least one of soybean protein isolate, whey protein, carboxymethyl cellulose, Arabic gum, xanthan gum, carrageenan and gelatin.

As a preferable scheme of the embodiment of the invention, the mass ratio of the maltodextrin to the auxiliary material is 1 (0.9-1.1).

As another preferable scheme of the embodiment of the invention, the auxiliary material is whey protein.

As another preferable scheme of the embodiment of the invention, the preparation method of the wormwood flavone comprises the following steps:

taking wormwood powder, and carrying out petroleum ether degreasing treatment on the wormwood powder;

mixing the wormwood powder subjected to degreasing treatment by petroleum ether with an ethanol aqueous solution, then performing oscillation extraction, and filtering to obtain an extracting solution;

after the extracting solution is subjected to deproteinization treatment, evaporating and concentrating to obtain a concentrated solution;

adsorbing and purifying the concentrated solution by using macroporous resin, and then eluting by using an ethanol water solution to obtain an eluent;

and (3) evaporating and concentrating the eluent, and then freeze-drying to obtain the wormwood flavone.

Another object of the embodiments of the present invention is to provide a method for preparing the above wormwood flavone microcapsule, which comprises the following steps:

mixing maltodextrin and auxiliary materials according to the mass ratio of 1 (0.8-1.6) to obtain a wall material for later use;

weighing wormwood flavone as a core material according to the mass ratio of (6-12) to 1 of the wall material to the core material, and dissolving the core material in ethanol to obtain an ethanol solution of the core material for later use;

adding an emulsifier and water into the wall material, uniformly mixing, and then mixing with an ethanol solution of the core material to obtain an emulsion;

and homogenizing the emulsion, and then carrying out spray drying treatment to obtain the wormwood flavone microcapsule.

In another preferred embodiment of the present invention, the emulsifier is soybean lecithin, and the addition amount thereof is 0.2% to 0.5% of the mass of the wall material.

In another preferable embodiment of the present invention, in the step, the solid content in the emulsion is controlled to be 15% to 25%, and the homogenization pressure for the homogenization treatment is 20 to 50 MPa.

As another preferable scheme of the embodiment of the present invention, in the step, the process conditions of the spray drying treatment are as follows: the feeding amount is 15-25 mL/min, the air inlet temperature is 170-200 ℃, and the air outlet temperature is 85-95 ℃.

The embodiment of the invention also aims to provide the wormwood flavone microcapsule prepared by the preparation method.

Another object of the embodiment of the present invention is to provide an application of the above wormwood flavone microcapsule in preparing a medicament.

According to the wormwood flavone microcapsule provided by the embodiment of the invention, wormwood flavone is taken as a core material, maltodextrin, soybean protein isolate, whey protein, carboxymethyl cellulose, Arabic gum, xanthan gum, carrageenan or gelatin and other auxiliary materials are taken as composite wall materials, the proportion of the core material to the wall materials is optimized, the proportion of the maltodextrin to the auxiliary materials is optimized, the embedding rate of the wormwood flavone microcapsule can be obviously improved, and the quality and the medicinal value of the wormwood flavone microcapsule can be improved.

Drawings

FIG. 1 is a graph of rutin standard curve.

FIG. 2 is a graph showing the effect of different homogenization pressures on the encapsulation efficiency of wormwood flavone microcapsules.

FIG. 3 is a graph showing the effect of different wall material ratios on the rate of encapsulation of flavonoids in wormwood microcapsules.

FIG. 4 is a graph showing the effect of different ratios of core material to wall material on the embedding rate of flavonoids in wormwood microcapsules.

FIG. 5 is a graph showing the effect of different soybean lecithin addition amounts on the encapsulation efficiency of wormwood flavone microcapsules.

FIG. 6 is a graph showing the effect of different solid contents on the embedding rate of wormwood flavone microcapsules.

FIG. 7 is a graph of the training results of BP neural networks.

FIG. 8 is a fitness variation curve for genetic algorithm optimization.

FIG. 9 is a graph showing the effect of different spray-dried feed rates on the encapsulation efficiency of wormwood flavone microcapsules.

FIG. 10 is a graph showing the effect of different spray-drying inlet air temperatures on the encapsulation efficiency of wormwood flavone microcapsules.

FIG. 11 is a graph showing the effect of different spray drying air-out temperatures on the encapsulation rate of wormwood flavone microcapsules.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

The reagents adopted in the following examples and experimental examples comprise:

rutin standard, China institute for drug and biological products; petroleum ether, absolute ethyl alcohol, chloroform, n-butyl alcohol, hydrochloric acid, sodium hydroxide, aluminum nitrate and sodium nitrite, wherein the reagents are analytically pure; maltodextrin (DE value 20), soy protein isolate, whey protein, carboxymethyl cellulose, gum arabic, xanthan gum, carrageenan, gelatin, and soybean lecithin, all of which are food grade.

The main instruments and equipment used include:

FW-100 high-speed universal pulverizer: beijing Zhongxing Weiwei instruments Inc.; FA1004 precision electronic analytical balance: shanghai balance instrumentation works; r-205 rotary evaporator: wuxi Shenke instruments, Inc.; PHS-3C precision pH meter: shanghai precision scientific instruments, Inc.; 101-2A electric heating air blast drying oven: beijing Zhongxing Weiwei instruments Inc.; SHA-C constant temperature water bath oscillator: shanghai yujin instruments, Inc.; TDL-40B desk-top high speed centrifuge: shanghai' an pavilion scientific instrument factory; SHZ-D circulating water type vacuum pump: consumer City Yaohua instruments, Inc.; BCD-219GSKZ refrigerator: new aircraft, inc, of south of the river; 752N uv-vis spectrophotometer: shanghai precision scientific instruments, Inc.; HWS-24 electric heating constant temperature water bath: Shanghai-Hengchang scientific instruments, Inc.; AB-8 macroporous resin: shanghai Mole speed scientific instruments, Inc.; 300mm × 16mm chromatography column: shanghai Mole speed scientific instruments, Inc.; TF-FD-1 vacuum freeze dryer: shanghai Denghui industry Co., Ltd; FRQ ultrasonic cleaner: hangzhou Frant ultrasonic science and technology, Inc.; GYB60-6S homogenizer: shanghai Donghua high pressure homogenizer factory; 2000P mini spray dryer: wuxi Waxin Instrument manufacturing Ltd.

Example 1

The embodiment provides a wormwood flavone microcapsule, and a preparation method of the wormwood flavone microcapsule comprises the following steps:

s1, mixing 1kg of maltodextrin with 0.98kg of auxiliary materials to obtain a wall material for later use; wherein the auxiliary material is whey protein.

S2, preparing wormwood flavone:

(1) pulverizing folium Artemisiae Argyi with high-speed universal pulverizer to obtain folium Artemisiae Argyi powder, sealing and storing.

(2) Defatting the folium Artemisiae Argyi powder with petroleum ether.

(3) Mixing 1kg of degreased folium Artemisiae Argyi powder with 27000L of 61 vol% ethanol water solution, and placing in a constant temperature water bath oscillator with temperature of 73 deg.C and oscillation speed of 120r/min for oscillation extraction for 90 min; then, the mixture was cooled to room temperature and filtered using a sand core funnel, and the filtrate was taken to obtain an extract.

(4) Deproteinizing the extractive solution by sevage method in the prior art, and refrigerating in a refrigerator at 4 deg.C for standing overnight; then, the filtrate was again filtered through a sand core funnel, and the filtrate was concentrated by a rotary evaporator until no alcohol smell was observed, and then concentrated until the mugwort flavonoids concentration was 1.0mg/mL, and the pH thereof was adjusted to 5.0, to obtain a concentrated solution.

(5) And (3) adsorbing and purifying the concentrated solution by using AB-8 macroporous resin (wherein the flow rate of the solution on the column is 1.0mL/min), eluting by using ethanol aqueous solution with pH of 8.42 and volume concentration of 68% at the flow rate of 1.5mL/min after the AB-8 macroporous resin is saturated by adsorption, and collecting the eluate.

(6) And (3) evaporating and concentrating the eluent by using a rotary evaporator, and then freeze-drying to obtain the wormwood flavone.

S3, weighing 100g of wormwood flavone as a core material, and ultrasonically dissolving the core material in a proper amount of ethanol to obtain an ethanol solution of the core material for later use.

S4, adding 2.364g of soybean lecithin and a proper amount of water into 1182g of the wall material, uniformly mixing, and uniformly mixing with the ethanol solution of the core material to obtain an emulsion, wherein the solid content of the emulsion is controlled to be 17.40%.

S5, homogenizing the emulsion in a homogenizer under the homogenizing pressure of 30MPa, and then performing spray drying in a spray dryer to obtain the wormwood flavone microcapsules. Wherein the process conditions of the spray drying treatment are as follows: the feeding amount is 20mL/min, the air inlet temperature is 180 ℃, and the air outlet temperature is 90 ℃.

Example 2

s1, mixing 1kg of maltodextrin with 0.8kg of auxiliary materials to obtain a wall material for later use; wherein the auxiliary materials are the mixture of whey protein, carboxymethyl cellulose and gelatin in equal mass ratio.

S2, preparing wormwood flavone:

(2) Defatting the folium Artemisiae Argyi powder with petroleum ether.

(3) Mixing 1kg of degreased folium Artemisiae Argyi powder with 25000L of 58% ethanol water solution, and placing in a constant temperature water bath oscillator at 70 deg.C and 100r/min oscillation speed for oscillation extraction for 80 min; then, the mixture was cooled to room temperature and filtered using a sand core funnel, and the filtrate was taken to obtain an extract.

(4) Deproteinizing the extractive solution by sevage method in the prior art, and refrigerating in a refrigerator at 4 deg.C for standing overnight; then, the filtrate was again filtered through a sand core funnel, and the filtrate was concentrated by a rotary evaporator until no alcohol smell was observed, and then concentrated continuously until the mugwort flavonoids concentration was 0.8mg/mL, and the pH thereof was adjusted to 5.0, to obtain a concentrated solution.

S4, adding 1.2g of soybean lecithin and a proper amount of water into 600g of the wall material, uniformly mixing, and uniformly mixing with the ethanol solution of the core material to obtain an emulsion, wherein the solid content of the emulsion is controlled to be 15%.

S5, homogenizing the emulsion in a homogenizer at a homogenizing pressure of 20MPa, and then spray-drying in a spray dryer to obtain the wormwood flavone microcapsules. Wherein the process conditions of the spray drying treatment are as follows: the feeding amount is 15mL/min, the air inlet temperature is 170 ℃, and the air outlet temperature is 85 ℃.

Example 3

s1, mixing 1kg of maltodextrin and 1.6kg of auxiliary materials to obtain a wall material for later use; wherein the auxiliary materials are the mixture of soybean protein isolate and Arabic gum in equal mass ratio.

S2, preparing wormwood flavone:

(2) Defatting the folium Artemisiae Argyi powder with petroleum ether.

(3) Mixing 1kg of degreased folium Artemisiae Argyi powder with 30000L of 65% ethanol water solution, and placing in a constant temperature water bath oscillator at 75 deg.C and oscillation speed of 140r/min for oscillation extraction for 100 min; then, the mixture was cooled to room temperature and filtered using a sand core funnel, and the filtrate was taken to obtain an extract.

(4) Deproteinizing the extractive solution by sevage method in the prior art, and refrigerating in a refrigerator at 4 deg.C for standing overnight; then, the filtrate was again filtered through a sand core funnel, and the filtrate was concentrated by a rotary evaporator until no alcohol smell was observed, and then concentrated continuously until the mugwort flavonoids concentration was 1.2mg/mL, and the pH thereof was adjusted to 5.0, to obtain a concentrated solution.

S4, adding 6g of soybean lecithin and a proper amount of water into 1200g of the wall material, uniformly mixing, and uniformly mixing with the ethanol solution of the core material to obtain an emulsion, wherein the solid content of the emulsion is controlled to be 25%.

S5, homogenizing the emulsion in a homogenizer under a homogenizing pressure of 50MPa, and then spray-drying in a spray dryer to obtain the wormwood flavone microcapsules. Wherein the process conditions of the spray drying treatment are as follows: the feeding amount is 25mL/min, the air inlet temperature is 200 ℃, and the air outlet temperature is 95 ℃.

Example 4

s1, mixing 1kg of maltodextrin with 0.9kg of auxiliary materials to obtain a wall material for later use; wherein the auxiliary materials are a mixture of xanthan gum and carrageenan in equal mass ratio.

S2, preparing wormwood flavone according to the method provided in the example 1.

S4, adding 2.4g of soybean lecithin and a proper amount of water into 800g of the wall material, uniformly mixing, and uniformly mixing with the ethanol solution of the core material to obtain an emulsion, wherein the solid content of the emulsion is controlled to be 18%.

S5, homogenizing the emulsion in a homogenizer at a homogenizing pressure of 40MPa, and then performing spray drying in a spray dryer to obtain the wormwood flavone microcapsules. Wherein the process conditions of the spray drying treatment are as follows: the feeding amount is 18mL/min, the air inlet temperature is 180 ℃, and the air outlet temperature is 88 ℃.

Example 5

s1, mixing 1kg of maltodextrin and 1.1kg of auxiliary materials to obtain a wall material for later use; wherein the auxiliary material is soybean protein isolate.

S4, adding 4g of soybean lecithin and a proper amount of water into 1000g of the wall material, uniformly mixing, and uniformly mixing with the ethanol solution of the core material to obtain an emulsion, wherein the solid content of the emulsion is controlled to be 22%.

S5, homogenizing the emulsion in a homogenizer at a homogenizing pressure of 35MPa, and then spray-drying in a spray dryer to obtain the wormwood flavone microcapsules. Wherein the process conditions of the spray drying treatment are as follows: the feeding amount is 22mL/min, the air inlet temperature is 190 ℃, and the air outlet temperature is 92 ℃.

Test example:

the first test method comprises the following steps:

1. influence of different composite wall materials on the embedding rate of the wormwood flavone microcapsules:

according to the preparation method provided by the embodiment 1, the maltodextrin is used as a main wall material, and the soybean protein isolate, the whey protein, the carboxymethyl cellulose, the arabic gum, the xanthan gum, the carrageenan, the gelatin and the like are respectively selected and compounded with the maltodextrin in a ratio of 1: 1; according to the mass ratio of the core material to the wall material of 1:9, the addition amount of the soybean lecithin of 0.3 percent and the total solid content of 20 percent, homogenizing, spray drying is carried out after homogenization, and 7 wall material combinations are investigated by taking the embedding rate of the wormwood flavone microcapsules as an index.

2. Influence of homogenization pressure on the encapsulation rate of wormwood flavone microcapsules:

according to the preparation method provided by the above example 1, the composite wall material is prepared by whey protein and maltodextrin in a ratio of 1: 1; according to the mass ratio of the core material to the wall material of 1:9, the addition amount of the soybean lecithin of 0.3 percent and the total solid content of 20 percent, homogenizing treatment is respectively carried out under the homogenizing pressure of 10 MPa, 20MPa, 30MPa, 40MPa and 50MPa, spray drying is carried out after homogenization, and the homogenizing pressure is examined by taking the wormwood flavone microcapsule embedding rate as an index.

3. Study on spray-dried raw material formula

3.1 Single factor test design

(1) Influence of wall material ratio on microcapsule embedding rate:

according to the preparation method provided in the above example 1, the whey protein and maltodextrin are respectively prepared into composite wall materials in the ratio of 0.6:1, 0.8:1, 1:1, 1.2:1, 1.4:1 and 1.6: 1; according to the mass ratio of the core material to the wall material of 1:9, the addition amount of soybean lecithin of 0.3 percent and the total solid content of 20 percent, homogenizing, wherein the homogenizing pressure is 30MPa, spray drying is carried out after homogenization, and the proportion of the wall material is investigated by taking the embedding rate of the wormwood flavone microcapsules as an index.

(2) Influence of core material to wall material ratio on microcapsule embedding rate:

according to the preparation method provided by the above example 1, the composite wall material is prepared by whey protein and maltodextrin in a ratio of 1: 1; according to the mass ratio of the core material to the wall material of 1:3, 1:6, 1:9, 1:12, 1:15 and 1:18, the addition amount of soybean lecithin is 0.3 percent, the total solid content is 20 percent, the homogenization treatment is carried out, the homogenization pressure is 30MPa, the spray drying is carried out after the homogenization, and the proportion of the core material to the wall material is investigated by taking the embedding rate of the wormwood flavone microcapsules as an index.

(3) Influence of soybean lecithin addition amount on microcapsule embedding rate:

according to the preparation method provided by the above example 1, the composite wall material is prepared by whey protein and maltodextrin in a ratio of 1: 1; according to the mass ratio of the core material to the wall material of 1:9, the addition amounts of the soybean lecithin are respectively 0.1%, 0.2%, 0.3%, 0.4% and 0.5%, and the total solid content is 20%, homogenizing treatment is carried out, the homogenizing pressure is 30MPa, spray drying is carried out after homogenizing, and the addition amount of the soybean lecithin is considered by taking the wormwood flavone microcapsule embedding rate as an index.

(4) Influence of solid content on the embedding rate of the microcapsules:

according to the preparation method provided by the above example 1, the composite wall material is prepared by whey protein and maltodextrin in a ratio of 1: 1; according to the mass ratio of the core material to the wall material of 1:9, the addition amount of the soybean lecithin of 0.3 percent and the total solid content of 10 percent, 15 percent, 20 percent, 25 percent and 30 percent respectively, homogenizing treatment is carried out, the homogenizing pressure is 30MPa, spray drying is carried out after homogenization, and the addition amount of the soybean lecithin is considered by taking the encapsulation rate of the wormwood flavone microcapsule as an index.

3.2 orthogonal design of experiments

According to the single-factor test result of the spray drying raw material formula, 3 optimal levels are selected for each factor, and 4-factor 3 level L9 (3) is carried out by taking the wormwood flavone microcapsule embedding rate as an index⁴) Orthogonal testThe factor level table is shown in table 1.

TABLE 1

3.3 BP neural network modeling and genetic algorithm optimization spray drying raw material formula

(1) BP neural network modeling:

taking all data of the orthogonal test result as learning samples of the BP neural network, wherein 4 main factors are used for influencing the formula of the spray drying raw material, namely the proportion of wall materials, the proportion of core materials to the wall materials, the addition amount of soybean lecithin and the content of solid matters, so that the number of neurons in an input layer is set to be 4; the number of indexes to be optimized is 1, namely the wormwood flavone microcapsule embedding rate, so that the number of neurons in an output layer is set to be 1; the number of the middle layer neurons between the input layer and the output layer is set to be 8 according to the experience; therefore, the topological structure of the whole BP neural network is 4-8-1. The transfer functions of the neurons of the input layer and the middle layer adopt radbas, and the transfer functions of the neurons of the middle layer and the output layer adopt satlin.

(2) Optimizing a spray drying raw material formula by a genetic algorithm:

and (3) taking the output value of the BP neural network which is completed with learning and training as a solving objective function of the genetic algorithm, and encoding by adopting actual horizontal data of each factor in the orthogonal test. All initial weights of the BP neural network are used as a population, a new genotype and a new population are generated between individuals of each generation through two-point crossing (crossing probability 0.3) and single-point variation (variation probability 0.1), selection, crossing and variation operations are performed in a circulating mode, excellent genes with the largest fitness value (namely wormwood flavone microcapsule embedding rate) are selected through a random sampling function, and a spray drying raw material formula optimized by a genetic algorithm is obtained.

4. Study of spray drying Process parameters

4.1, influence of the feeding amount of spray drying on the embedding rate of the wormwood flavone microcapsules:

according to the preparation method provided by the above example 1, the composite wall material is prepared by whey protein and maltodextrin in a ratio of 0.98: 1; according to the method, the soybean lecithin addition amount is 0.20%, the mass ratio of a core material to a wall material is 1:11.82, the total solid content is 17.40%, homogenization treatment is carried out, the homogenization pressure is 30MPa, spray drying is carried out after homogenization, the air inlet temperature is 180 ℃, the air outlet temperature is 90 ℃, the embedding rate is taken as an index, and the influence of the feed flow rate of 15, 20, 25, 30 and 35mL/min on the microcapsule embedding rate is respectively examined.

4.2, influence of spray drying air inlet temperature on the embedding rate of the microcapsules:

according to the preparation method provided by the above example 1, the composite wall material is prepared by whey protein and maltodextrin in a ratio of 0.98: 1; according to the addition of 0.20 percent of soybean lecithin, the mass ratio of a core material to a wall material of 1:11.82 and the total solid content of 17.40 percent, carrying out homogenization treatment under the homogenization pressure of 30MPa, carrying out spray drying after homogenization, wherein the feeding flow rate is 20mL/min, the air outlet temperature is 90 ℃, and the influence of the air inlet temperature of 170 ℃, 180 ℃, 190 ℃, 200 and 210 ℃ on the microcapsule embedding rate is respectively examined by taking the embedding rate as an index.

4.3, influence of spray drying air-out temperature on the embedding rate of the microcapsules:

according to the preparation method provided by the above example 1, the composite wall material is prepared by whey protein and maltodextrin in a ratio of 0.98: 1; according to the addition of 0.20 percent of soybean lecithin, the mass ratio of a core material to a wall material of 1:11.82 and the total solid content of 17.40 percent, carrying out homogenization treatment under the homogenization pressure of 30MPa, carrying out spray drying after homogenization, wherein the feeding flow rate is 20mL/min, the air inlet temperature is 180 ℃, and the influence of the air outlet temperature of 80, 85, 90, 95, 100 and 105 ℃ on the microcapsule embedding rate is respectively examined by taking the embedding rate as an index.

5. Determination of wormwood flavone microcapsule embedding rate (in terms of rutin)

5.1, drawing a rutin standard curve:

accurately weighing 15mg of rutin standard product dried to constant weight at 105 ℃, dissolving with 80% ethanol to 100mL of constant volume to obtain 0.15mg/mL of rutin standard solution, precisely sucking 0.0mL, 1.0mL, 2.0mL, 3.0mL, 4.0mL, 5.0mL and 6.0mL of rutin standard solution in 7 clean 20mL scale test tubes, and respectively adding 6.0mL of rutin standard solution into the 7 scale test tubes containing the rutin standard solutionmL, 5.0mL, 4.0mL, 3.0mL, 2.0mL, 1.0mL, 0.0mL of 80% ethanol solution, then 5% NaNO was added to each graduated tube₂After 1.0mL of the solution was sufficiently shaken and allowed to stand for 6min, 10% Al (NO) was added to each graduated tube₃)₃And (3) 1.0mL of solution, fully oscillating, standing for 6min, adding 10.0mL of 10% NaOH solution into each graduated tube, metering the volume to the graduated position of 20mL graduated tubes by using 80% ethanol, fully oscillating, standing for 15min, and measuring the absorbance at the wavelength of 507 nm.

5.2, determining the content of wormwood flavone on the surface of wormwood flavone microcapsules:

accurately weighing 0.01g of wormwood flavone microcapsule sample, adding 15mL of absolute ethyl alcohol, shaking to fully dissolve the wormwood flavone microcapsule sample, filtering by using a sand core funnel, collecting filtrate, washing filter residues twice by using 10mL of absolute ethyl alcohol, combining the filtrates, taking a proper amount of filtrate, measuring absorbance according to a standard curve preparation method, and calculating wormwood flavone content (in terms of rutin) on the microcapsule surface.

5.3, determining the content of wormwood flavone in the wormwood flavone microcapsules:

accurately weighing 0.01g of wormwood flavone microcapsule sample, adding 15mL of 80% ethanol, carrying out ultrasonic dissolution, filtering by using a sand core funnel, collecting filtrate, washing filter residues twice by using 10mL of 80% ethanol, combining the filtrates, taking a proper amount of filtrate, measuring absorbance according to a standard curve preparation method, and calculating wormwood flavone content (in terms of rutin) in the microcapsule.

5.4 the formula for the calculation of the embedding rate is as follows:

the embedding rate (%) × (1-content of flavonoids in the surface of the microcapsule/total amount of flavonoids in the microcapsule) x 100%.

Second, test results and analysis

1. The rutin standard curve is plotted as shown in figure 1. The unary linear regression equation between the absorbance and the rutin content obtained from the test results is:

Y＝0.3395x+0.0078；

wherein, Y: absorbance value under 507 nm; x: content of flavone (mg/mL); calculated, the correlation coefficient is: r²Regression was extremely significant at 0.9975. Therefore, the concentration of the surfactant is in the range of 0 to 0.9mg/mLThe regression equation can be used for calculating the flavone content of the microcapsule sample.

2. The influence of different composite wall materials on the embedding rate of the wormwood flavone microcapsules is shown in table 2.

TABLE 2

As can be seen from table 2, compared with other groups of composite wall materials, the wall material combination of whey protein and maltodextrin has higher embedding rate of microcapsules after spray drying, and the microcapsule sample particles are uniform, fine and smooth without agglomeration, so that the subsequent experiments adopt the composite wall material of whey protein and maltodextrin to perform microencapsulation research.

3. The effect of homogenization pressure on the encapsulation efficiency of the wormwood flavone microcapsules is shown in the attached figure 2.

As can be seen from FIG. 2, with the increase of the homogenizing pressure, the materials are mixed more uniformly, the material system is more stable, and the embedding rate of the microcapsules is gradually increased. When the homogenizing pressure is more than 30MPa, the materials are possibly mixed sufficiently, the material system tends to be stable, the homogenizing pressure is increased, and the embedding rate of the microcapsules is not obviously increased.

4. The results of the study of the spray-dried raw material formulation are as follows:

4.1 Single factor test results

(1) The influence of the wall material ratio on the wormwood flavone microcapsule embedding rate is shown in figure 3.

As can be seen from fig. 3, with the increase of the proportion of whey protein in the composite wall material, the embedding rate of the microcapsule is significantly increased, probably because whey protein has better emulsifying property and film-forming property, a smooth film layer can be formed on the surface of the micro-droplet core material during spray drying, and maltodextrin is coated outside the film layer through spray drying, so as to prevent the micro-droplet core material from diffusing to the outer layer. When the ratio of the whey protein in the composite wall material is more than 1:1, the viscosity of a material system is too high, evaporation of water during spray drying is not facilitated, the generation rate of the microcapsule wall is reduced, and the embedding rate of the microcapsule is reduced.

(2) The influence of the ratio of core material to wall material on the embedding rate of folium Artemisiae Argyi flavone microcapsule is shown in figure 4.

As can be seen from fig. 4, as the proportion of the wall material increases, the amount of the wall material increases, so that the emulsion film on the surface of the core material of the micro-droplet can be rapidly solidified outside the film during spray drying, and the embedding rate of the micro-capsule gradually increases. When the ratio of the core material to the wall material of the micro-droplets is less than 1:9 and the use amount of the wall material is large, the viscosity of the material system is gradually increased probably because the use amount of the wall material is continuously increased, so that the micro-droplets are not atomized, and the embedding rate of the micro-capsules is reduced.

(3) The effect of the addition of soybean lecithin on the encapsulation efficiency of the wormwood flavone microcapsules is shown in the attached figure 5.

As can be seen from FIG. 5, with the increase of the addition amount of the emulsifier, it is probably because the emulsion formed by homogenizing the material system is more uniform under the action of the emulsifier, and the embedding rate of the microcapsule is gradually increased with the increase of the emulsifier dosage. When the addition amount of the emulsifier is 0.3%, the whole material emulsion system is in a uniform and stable state after homogenization possibly, the addition amount of the emulsifier is continuously increased, and the embedding rate of the microcapsule after homogenization and spray drying is not obviously improved.

(4) The effect of solid content on the encapsulation rate of the wormwood flavone microcapsules is shown in figure 6.

As can be seen from fig. 6, the embedding rate of the microcapsules gradually increases with the increase of the solid content in the system, and the increase of the solid content may increase the viscosity of the material system, which is beneficial to the formation of the capsule wall and the coating of the micro-droplets during the spray drying. When the solid content in the system is more than 20%, the viscosity of the material system is high, so that the material system is easy to stick to the wall during spray drying, atomization of micro-droplets is not facilitated, and the embedding rate of the micro-capsules is obviously reduced.

4.2, the results of the orthogonality test are shown in Table 3 below.

TABLE 3

Analyzing the results of the orthogonal test in the table 3, and determining that the main and secondary sequence of the influence of different factors in the spray drying raw material formula on the wormwood flavone microcapsule embedding rate is as follows according to the magnitude of the range R value: the proportion of wall materials (lactalbumin: maltodextrin) > the addition amount of soybean lecithin > the proportion of core materials to wall materials > the content of solid matters.

4.3, the curve of the training result of the BP neural network is shown in figure 7.

The data of the orthogonal test results are used as learning and training samples of the BP neural network, and the error curve of the predicted value of the embedding rate of the wormwood flavone microcapsules in the learning and training processes of the BP neural network is shown in figure 7. As shown in the attached figure 7, with the increase of the learning and training times of the BP neural network, the error of the predicted value of the embedding rate of the wormwood flavone microcapsules is continuously reduced, and after 9988 times of learning and training, the error of the predicted value of the embedding rate of the wormwood flavone microcapsules by the BP neural network reaches the expected target 10^-3And after the training is finished, the trained BP neural network can be combined with a genetic algorithm to carry out theoretical prediction on the formula of the wormwood flavone microcapsule spray drying.

4.4, the optimization result of the genetic algorithm is shown in figure 8.

As can be seen from fig. 8, after 200 generations of genetic iterative evolution, the fitness value (wormwood flavone microcapsule embedding rate) reaches the maximum value of 90.9139%, and the maximum fitness value (wormwood flavone microcapsule embedding rate) corresponds to the spray drying raw material formula, wherein the ratio of whey protein to maltodextrin is 0.9848:1, the addition amount of soybean lecithin is 0.2001%, the ratio of core material to wall material is 1:11.8202, and the solid content is 17.4019%.

4.5, verifying test results: in order to facilitate engineering operation, the result obtained by optimizing the genetic algorithm is properly corrected to determine the optimal formula of the spray drying raw material as follows: the ratio of whey protein to maltodextrin is 0.98:1, the addition amount of soybean lecithin is 0.20%, the ratio of core material to wall material is 1:11.82, and the solid content is 17.40%, and the average value of the embedding rate of the wormwood flavone microcapsules is 90.15% which is close to the theoretical predicted value of 90.9139% by carrying out three spray drying experiments according to the formula, so that the optimized formula can be applied to engineering practice.

5. The research results of the spray drying process parameters are as follows:

5.1, the effect of the amount of spray-dried feed on the rate of encapsulation of flavonoids in mugwort is shown in FIG. 9.

As can be seen from fig. 9, the microcapsule embedding rate is higher under the condition of a smaller feeding amount, probably because the feeding amount is smaller, the micro-droplet core material in the material system is rapidly atomized and coated by the wall material and dried in time during spray drying, and the loss of the micro-droplet core material is effectively reduced. Along with the gradual increase of the feeding amount, the atomization rate of the micro-droplet core material in the material system is increased, but the drying rate is relatively reduced, and the embedding rate of the microcapsule is reduced. Considering that the embedding rate is relatively high when the feeding amount is small, the production efficiency of the product is relatively low, and in order to ensure high production efficiency and enable microcapsules to have high embedding rate, the feeding amount is set to be 20mL/min during spray drying.

5.2, the influence of the air inlet temperature of the spray drying on the embedding rate of the wormwood flavone microcapsules is shown in the attached figure 10.

As can be seen from fig. 10, when the inlet air temperature is lower than 180 ℃, the embedding rate of the microcapsules is gradually increased along with the increase of the inlet air temperature, which may be unfavorable for the film formation on the surfaces of the micro-droplets when the inlet air temperature is lower, the water content of the microcapsules is relatively higher, and the embedding rate of the flavonoids in wormwood is actually lower. When the temperature of the inlet air is higher than 180 ℃, the evaporation rate of water is too fast possibly along with the rise of the temperature of the inlet air, so that the film forming property of the wall material is rapidly reduced, and the embedding rate of the microcapsule is obviously reduced. Therefore, the air inlet temperature is set to be 180 ℃ during spray drying.

5.3, the influence of the air outlet temperature of spray drying on the embedding rate of the wormwood flavone microcapsules is shown in the attached figure 11.

As can be seen from fig. 11, when the outlet air temperature is less than 90 ℃, the microcapsule embedding rate gradually increases with the outlet air temperature, and it is likely that under the condition of lower outlet air temperature, the heat load of the microcapsule is higher, the inner micro-droplet core material tends to expand outward, so that the partially formed microcapsule is broken, and the microcapsule embedding rate is lower; the conditions are gradually improved along with the increase of the temperature, and the embedding rate of the microcapsule is gradually increased. When the air outlet temperature is higher than 90 ℃, the formed microcapsule cracks due to excessive heating, and the microcapsule embedding rate is obviously reduced along with the temperature increase. Therefore, the air outlet temperature is set to be 90 ℃ during spray drying.

Third, conclusion

The method comprises the following steps of preparing a wormwood flavone crude extract by using wormwood as a raw material and adopting an ethanol solution oscillation extraction method, purifying the wormwood flavone crude extract by using AB-8 macroporous resin, freeze-drying the purified solution to prepare a wormwood flavone sample, and exploring a microencapsulation method of the wormwood flavone sample on the basis of comprehensively applying various methods and technologies, wherein the main conclusion is as follows:

(1) the composite wall material is formed by compounding soybean protein isolate, whey protein, carboxymethyl cellulose, Arabic gum, xanthan gum, carrageenan, gelatin and the like which are respectively selected as main wall materials with maltodextrin.

(2) The material system consisting of whey protein, maltodextrin, soybean lecithin, wormwood flavone and the like is homogenized under the pressure of 30MPa, and then the wormwood flavone microcapsule is prepared by spray drying, so that the method is economic.

(3) The single factor test and the orthogonal test are combined, the factors influencing the wormwood flavone microcapsule spray drying raw material formula are investigated, and the main and secondary sequence of the influence of the components in the spray drying raw material formula on the wormwood flavone microcapsule embedding rate is determined as follows: the proportion of wall materials (lactalbumin: maltodextrin) > the addition amount of soybean lecithin > the proportion of core materials to wall materials > the content of solid matters.

(4) Taking the data of the orthogonal test result as a learning and training sample of the BP neural network, and after 9988 times of learning and training, the error of the BP neural network on the predicted value of the wormwood flavone microcapsule embedding rate reaches the expected target 10^-3Will train the BP nerveThe network is combined with a genetic algorithm, and the theoretical prediction is carried out on the formula of the wormwood flavone microcapsule spray drying: when the proportion of whey protein to maltodextrin in the spray drying material system is 0.9848:1, the addition amount of soybean lecithin is 0.2001%, the proportion of core material to wall material is 1:11.8202, and the solid content is 17.4019%, homogenizing under 30MPa, and carrying out spray drying, wherein the theoretical maximum value of the embedding rate of the wormwood flavone microcapsules is 90.9139%.

(5) In order to facilitate engineering operation, the results obtained by optimizing the genetic algorithm are properly corrected, and the optimal formula of the spray drying raw materials is finally determined as follows: the ratio of whey protein to maltodextrin is 0.98:1, the addition amount of soybean lecithin is 0.20%, the ratio of core material to wall material is 1:11.82, and the solid content is 17.40%.

(6) On the basis of determining the optimal formula of the wormwood flavone microencapsulation spray drying raw material, the wormwood flavone microencapsulation spray drying process parameters are researched by adopting a step-by-step optimization method, and the optimal process parameters of the wormwood flavone microencapsulation spray drying are determined as follows: the feeding amount is 20mL/min, the air inlet temperature is 180 ℃, and the air outlet temperature is 90 ℃.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims

1. A wormwood flavone microcapsule is characterized by comprising:

core material, which is wormwood flavone; and

2. The wormwood flavone microcapsule as claimed in claim 1, wherein the mass ratio of the maltodextrin to the auxiliary material is 1 (0.9-1.1).

3. The wormwood flavone microcapsule according to claim 1 or 2, wherein the excipient is whey protein.

4. The wormwood flavone microcapsule according to claim 1, wherein the wormwood flavone preparation method comprises the following steps:

5. A method for preparing the wormwood flavone microcapsule according to any one of claims 1 to 4, comprising the following steps:

6. The preparation method of the wormwood flavone microcapsule as claimed in claim 5, wherein the emulsifier is soybean lecithin, and the addition amount of the emulsifier is 0.2-0.5% of the mass of the wall material.

7. The preparation method of the wormwood flavone microcapsule as claimed in claim 5, wherein in the step, the solid content in the emulsion is controlled to be 15% to 25%, and the homogenization pressure for homogenization is 20MPa to 50 MPa.

8. The preparation method of wormwood flavone micro-capsule according to claim 5, wherein in the step, the spray drying process conditions are as follows: the feeding amount is 15-25 mL/min, the air inlet temperature is 170-200 ℃, and the air outlet temperature is 85-95 ℃.

9. An wormwood flavone microcapsule prepared by the preparation method of any one of claims 5-8.

10. Use of the wormwood flavone micro capsules as defined in any one of claims 1 to 4 and 9 for the manufacture of a medicament.