CN113842375A

CN113842375A - Microcapsule with gradient capsule wall structure and preparation method thereof

Info

Publication number: CN113842375A
Application number: CN202111190826.5A
Authority: CN
Inventors: 倪卓
Original assignee: Shenzhen Huabao Biomaterial Technology Co ltd
Current assignee: Tuoteng Huabao (Suzhou) Biotechnology Co.,Ltd.
Priority date: 2021-10-13
Filing date: 2021-10-13
Publication date: 2021-12-28
Anticipated expiration: 2041-10-13
Also published as: CN113842375B

Abstract

The invention provides a microcapsule with a gradient capsule wall structure and a preparation method thereof. The outermost layer reacts with glutaraldehyde firstly, the crosslinking degree is highest, a harder crosslinked shell structure is formed, the closer to the interior of the core material, the crosslinking degree is reduced, and the strength of the capsule shell is reduced, so that a microcapsule shell structure with gradient hardness is formed; the microcapsule has high shell strength, low internal strength, high strength, toughness and elasticity, is favorable for keeping good appearance and stability in the application process of the microcapsule, avoids the leakage of capsule core substances, effectively protects the capsule core, slowly releases the capsule core and prolongs the activity and efficacy of the capsule core.

Description

Microcapsule with gradient capsule wall structure and preparation method thereof

Technical Field

The invention relates to the technical field of microcapsule preparation, in particular to an oil-encapsulated microcapsule and a preparation method thereof.

Background

Sodium alginate is a by-product obtained after extracting iodine and mannitol from brown algae such as kelp or gulfweed, is a natural linear anionic polymer polysaccharide, mainly comprises sodium salt of alginic acid, and is a main commercial product of alginic acid. In the prior art, sodium alginate hydrogel and SIS are compounded to be used as a support material, and cartilage cells are inoculated to construct the tissue engineering cartilage to repair the rabbit full-thickness articular cartilage defect. Randomly dividing rabbits with proper age into an experimental group and a control group, placing the composite material at the defect of the experimental group, and sewing and covering a layer of SIS film on the surface of the composite material to completely fill the defect; the control group was sutured with a simple sodium alginate hydrogel filled, covered with an SIS film. The experiment result shows that the sodium alginate and SIS composite material has the function of promoting the regeneration of cartilage tissues.

Chitosan hydrogel is often used in wound dressings because of its antimicrobial properties. Chitosan/polyglycolic acid sponge containing nano silver/polyethylene glycol is prepared by taking silver nitrate, polyethylene glycol and chitosan as raw materials through acetalization reaction by Chitosan Kangkang and the like, and the performance and the structure of the material are detected. The result and conclusion are that the nano silver particles released by the prepared sponge have good antibacterial performance, so that the sponge has good antibacterial performance. The dressing has good physical properties, biocompatibility and sterilization effect.

The properties of the wall material adopted for preparing the microcapsule in the prior art determine the specific application mode of the microcapsule, and how to prepare the wall material with excellent mechanical properties becomes a technical problem to be solved urgently by the technical personnel in the field.

Disclosure of Invention

The invention aims to solve the defects of the prior art and provides a microcapsule with a gradient wall structure and a preparation method thereof.

In order to achieve the purpose, the invention provides a microcapsule with a gradient capsule wall structure, which comprises a wall material and an oily capsule core substance, and is characterized in that the wall material is a polymer formed by crosslinking chitosan/sodium alginate with glutaraldehyde, and the chemical structural formula of the polymer is shown as a formula (I):

the invention also provides a preparation method of the microcapsule with the gradient capsule wall structure, which comprises the following steps:

a. dissolving sodium alginate in an acetic acid solution to obtain a sodium alginate solution;

b. dissolving chitosan in an acetic acid solution to obtain a chitosan solution;

c. dissolving sucrose fatty acid ester in oily capsule core substance to obtain oily mixed solution;

d. adding the oily mixed solution in the step c into the chitosan mixed solution in the step b, and fully emulsifying to obtain a mixed emulsion;

e. adding an acetic acid solution into the mixed emulsion obtained in the step d for dilution;

f. dropwise adding the sodium alginate solution obtained in the step a into the emulsion obtained in the step e, and stirring and dropwise adding at the temperature of 25-30 ℃;

g. adding a calcium chloride solution into the reaction system in the step f, stopping dripping when insoluble substances appear in the solution, and completely reacting;

h. and g, adding excessive glutaraldehyde aqueous solution into the reaction system in the step g, and reacting completely to obtain the microcapsule with the gradient capsule wall structure.

Preferably, the oily capsule core material is one or more of corn oil, olive oil, soybean oil, fish oil, oily essence and oily probiotics.

Preferably, the step c specifically includes: stirring the sucrose fatty acid ester and the oily cystic substance at the temperature of 25-30 ℃ and the rpm of 800 for 5-10 min.

Preferably, the step d specifically includes: the emulsification temperature is 25-30 ℃, the emulsification time is 30min, and the stirring speed is 600-800 rpm.

Preferably, the step f specifically includes: and (b) dropwise adding the sodium alginate aqueous solution obtained in the step (a) into the mixed emulsion obtained in the step (e) under stirring at the temperature of 25-30 ℃, controlling the dropwise adding speed to be 1mL/min, controlling the stirring speed to be 800rpm, adjusting the pH value to be 5.5, and reacting for 60 min.

Preferably, the concentration of the calcium chloride solution in the step g is 0.3-0.4mol/L, the dropping speed of the calcium chloride solution is controlled to be 1mL/min, when insoluble substances appear in the solution, the dropping is stopped, and the curing reaction is carried out for 30min at 50 ℃.

Preferably, the mass fraction of the glutaraldehyde solution in the step h is 25%.

Preferably, the step h is followed by adding deionized water into the reaction system for suction filtration and washing to remove unreacted glutaraldehyde, so as to obtain the microcapsule with the gradient capsule wall structure.

Preferably, the ratio of each component is calculated by mass fraction: 60-70 parts of sodium alginate, 60-70 parts of chitosan, 8-15 parts of oily capsule core substances, 0.3-0.6 part of sucrose fatty acid ester, 15-30 parts of calcium chloride and 7-10 parts of glutaraldehyde.

Compared with the prior art, the preparation method has the beneficial effects that the microcapsule with the gradient capsule wall structure is prepared by using excessive cross-linking agent and controlling the process, and the hardness of the gradient capsule wall structure is increased from inside to outside because of different cross-linking degrees from outside to inside. The outermost layer reacts with glutaraldehyde firstly, the degree of crosslinking is highest, a hard crosslinked shell structure is formed, the closer to the interior of the core material, the degree of crosslinking is reduced, and the strength of the capsule shell is reduced, so that a microcapsule shell structure with gradient hardness is formed; the microcapsule has high shell strength, low internal strength, high strength, toughness and elasticity, is favorable for keeping good appearance and stability in the application process of the microcapsule, avoids the leakage of capsule core substances, effectively protects the capsule core, slowly releases the capsule core and prolongs the activity and efficacy of the capsule core.

Drawings

FIG. 1 is a graph of pH and corresponding conductivity for solutions of chitosan and sodium alginate in example 2.

Fig. 2 is a graph of the effect of calcium chloride concentration on the conductivity peak for example 2.

FIG. 3 is a graph showing the effect of calcium chloride concentration on the change in conductivity in example 2.

Fig. 4 is a schematic structural view of the microcapsule prepared in example 1.

FIG. 5 is a thermogravimetric plot of chitosan, sodium alginate and the microcapsules prepared in example 1.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention.

Example 1 preparation of microcapsules with gradient wall Structure

This example illustrates the detailed preparation of microcapsules with a gradient wall structure as follows:

a. weighing a certain mass of sodium alginate, adding 100mL of deionized water and 1mL of acetic acid solution, stirring for dissolving, and swelling for 8 hours to obtain a sodium alginate solution;

b. weighing chitosan with a certain mass, adding 100mL of deionized water and 1mL of acetic acid solution, and stirring to dissolve completely to obtain a chitosan mixed solution;

c. adding a certain mass of oily substances and emulsifier sucrose fatty acid ester into a three-mouth beaker, and stirring for 5min at room temperature and the stirring speed of 800 rpm; obtaining an oily mixed solution;

d. adding the oily mixed solution in the step c into the chitosan mixed solution in the step b, and stirring at 800rpm for 30min at room temperature to obtain a mixed emulsion;

e. adding 30mL of water into the three-neck baked cake, dropwise adding 0.3mL of acetic acid, respectively dropwise adding the sodium alginate solution, the chitosan mixed solution and the mixed emulsion into a three-neck flask at room temperature, dropwise adding 1mL of the mixed solution at the dropwise adding speed of 1min, stirring at 800rpm, adjusting the pH value to 5.5, and carrying out complex coacervation reaction for 60 min; protonating free amino groups on chitosan to form-NH in an acidic medium at pH 5.5₃ ⁺The molecular chain is provided with a large amount of positive charges, and the sodium alginate molecules are provided with a large amount of carboxyl groups with negative charges, so that a polyelectrolyte film is formed under certain pH value of the chitosan and the sodium alginate due to the electrostatic interaction between the positive charges and the negative charges, so that the complex coacervation is carried out, and the stability of the microcapsule is improved;

in the step, the electrostatic interaction reaction formula of the chitosan and the sodium alginate is as follows:

f. is turned to the reverse directionAdding 0.3604mol/L calcium chloride solution into the system, wherein the dripping speed is 1mL/min, stopping dripping when insoluble substances appear in the solution, and controlling the temperature to be 50-60 ℃ for curing reaction for 30 min; na on sodium alginate G segment⁺With Ca²⁺Ion exchange is carried out to form hydrogel with an egg box structure, and calcium chloride generates coordination with hydroxyl, amino and glycosidic bond on sodium alginate to form the egg box structure;

in the step, the reaction formula of the reaction process of the sodium alginate and the calcium chloride is as follows:

g. and f, adding excessive 25% glutaraldehyde solution into the reaction system in the step f, reacting glutaraldehyde with free amino and hydroxyl on the chitosan, and curing at room temperature for 20min to obtain the chitosan/sodium alginate microcapsule, wherein the shell structure of the microcapsule is characterized in that the hardness is increased from inside to outside because of different crosslinking degrees from outside to inside. The outermost layer reacts with glutaraldehyde firstly, the crosslinking degree is highest, a harder crosslinked shell structure is formed, the closer to the interior of the core material, the crosslinking degree is reduced, and the shell strength is reduced, so that a microcapsule shell structure with gradient hardness is formed;

in the step, the structural formula obtained by cross-linking reaction of glutaraldehyde and chitosan is as follows:

h. and g, adding deionized water into the reaction system for suction filtration and washing to remove unreacted glutaraldehyde and obtain the microcapsule with the gradient capsule wall structure.

EXAMPLE 2 isoelectric Point and conductivity measurements

In the experiment, 1.0% NaOH solution and HCl solution are adopted to adjust the pH value of the solution to be measured, an acidity tester is used to measure the pH value of the solution, and a conductivity tester is used to measure the conductivity change of the solution, so that the relationship between the pH value and the conductivity of the solution to be measured is obtained.

Weighing 1.00g of sodium alginate, adding the sodium alginate into a beaker, adding 100mL of deionized water, placing the beaker into a heat collection type constant temperature heating magnetic stirrer, controlling the water bath temperature to be 60 ℃, stirring the mixture at a magnetic stirring speed of 150rpm until the mixture is fully dissolved, naturally cooling the mixture until bubbles disappear, marking the mixture as a 1% sodium alginate solution, preparing 5 parts of the mixture for later use under the same conditions, and swelling the mixture for 8 hours for later use under natural conditions. Adding 100.0mL of 1% acetic acid solution into a 200mL beaker, heating in a water bath at a constant temperature of 50 ℃, stirring at the speed of 200rpm, weighing 1.00g of chitosan, adding into the beaker, dropwise adding 1.00mL of chitosan, stirring until the chitosan is dissolved to obtain 1.0% chitosan solution, and preparing 5 parts for later use under the same conditions.

A50.0 mL, 1.0% chitosan solution was taken to a 100mL beaker and the pH was gradually adjusted to 3.0 using 1.0% HCl solution, with the relationship between pH and conductivity being recorded every 5 drops. Another 50.0mL of 1.0% chitosan solution was added to a 100mL beaker, the pH was gradually adjusted to 11.0 using 1.0% NaOH solution, and the relationship between pH and conductivity was recorded every 5 drops. The relationship between the pH value and the conductivity of 1.0% sodium alginate was measured under the same conditions.

Taking 45.0mL of 1.0% chitosan solution and 5.0mL of 3.0% CaCl₂The solution was brought to a 100mL beaker and the pH was gradually adjusted to 3.0 using 1.0% HCl solution, and the relationship between pH and conductivity was recorded every 5 drops. Another 50.0mL of 1.0% chitosan solution was added to a 100mL beaker, the pH was gradually adjusted to 11.0 using 1% NaOH solution, and the relationship between pH and conductivity was recorded every 5 drops. 40.0mL of 1.0% chitosan solution and 10.0mL, 1.0% CaCl were measured under the same conditions₂Mixed solution, 25.0mL, 1.0% chitosan solution and 25.0mL, 1.0% CaCl₂Mixed solution, 20.0mL, 1.0% chitosan solution and 30.0mL, 1.0% CaCl₂The relationship between the pH value and the conductivity of the mixed solution.

The pH values and the corresponding conductivities of the chitosan and sodium alginate solutions measured by the experiment are plotted as shown in the attached figure 1. As can be seen from FIG. 1, when the conductivity of the sodium alginate solution is higher than pH 4.7, the conductivity of the sodium alginate solution increases with the increase of pH, and the conductivity of the solution changes greatly, which indicates that the-COOH groups in the sodium alginate in the solution are continuously dissociated and the-COO groups in the sodium alginate solution are continuously dissociated^-Increase in quantityAdding; when the pH value is 3-4.1, the electric conductivity of the sodium alginate solution is reduced by a range less than the pH value more than 4.7-7, because H is in the process of adjusting the pH value⁺And Cl^-The increase in the amount results in an increase in the conductivity of the solution, -COO^-The ability to convert to-COOH is reduced, so that the isoelectric point of sodium alginate can be determined to be in the pH range of 4.1-4.7, at which time the sodium alginate solution is-COO^-Near the minimum, there is only a very small further decrease in pH-COO^-When the sodium alginate is converted into-COOH, the sodium alginate molecules are kept neutral, and when the pH value is more than the interval, a large number of-COOH groups are continuously dissociated into-COO^-And therefore the sodium alginate molecule is negatively charged.

The chitosan molecule contains-NH₂The group will be protonated to form-NH in an acidic environment₃ ⁺Ions, which are dissolved under acidic conditions, increase the conductivity of the solution, and as can be seen from FIG. 1, when the pH value is less than 6, the conductivity of the chitosan solution increases along with the decrease of the pH value, the conductivity of the solution changes greatly, which shows that the quantity of chitosan in the solution increases and protonation forms-NH₃ ⁺The ions increase. When the pH value is in the range of 6-6.7, the conductivity of the solution is slightly changed, which shows that the chitosan amount in the chitosan solution is not obviously changed at the moment and reaches a saturated state. At a pH above 6.7, the conductivity increases more slowly with increasing pH, which is-OH during pH adjustment^-And Na⁺The increase in the amount causes the increase in the conductivity of the solution, but the increase is negligible compared to the decrease in conductivity below pH 6, so that it can be determined that the isoelectric point of chitosan is in the pH range of 6-6.7, below which the chitosan molecule is present in large amounts due to the presence of-NH₃ ⁺The chitosan molecules are precipitated due to the decrease in solubility and remain neutral in the range of positive charge.

By adding CaCl with different concentrations into chitosan solution₂Testing the conductivity of the sample to obtain CaCl₂The effect of concentration on the conductivity peak is shown in FIG. 2, CaCl₂The effect of concentration on the change in conductivity is shown in FIG. 3. from FIGS. 2 and 3, it can be seen that CaCl is not added₂The isoelectric point of the chitosan solutionpH 5.5, CaCl addition without volume change₂The content of (A) does not change the isoelectric point of the solution, but the conductivity peak value of the solution is increased and follows CaCl₂The trend of the ratio increase in the solution is shown in FIG. 2, which demonstrates that Cl in the mixed solution is present at a constant volume of the solution^-And Ca²⁺The increase in ion solubility may increase the conductivity peak.

As can be seen from FIG. 3, Cl was contained in the mixed solution^-And Ca²⁺The difference between the conductivity peak value and the conductivity minimum value also exists when the ion concentration is increased, and the difference is along with the Cl in the mixed solution^-And Ca²⁺The ion concentration is increased, the conductivity change value is increased firstly and then decreased, the highest value is reached when the mass ratio of the chitosan to the calcium chloride is 1:0.5, and CaCl is added under the condition of the ratio₂The chitosan ionization is promoted to a certain extent, and the reaction can be promoted in the process of preparing the gel by the complex coacervation method. When the ratio of chitosan to calcium chloride is more than 1, in the pH range of 4-10, the conductivity change of the solution is more gentle than that of a single-component chitosan solution, and the difference value of the conductivity is smaller because the ratio of chitosan in the mixed solution is reduced and Cl is reduced^-And Ca²⁺The ionic conductivity is strong, so the conductivity change is relatively small, and the high concentration of calcium chloride is not beneficial to the complex coacervation method.

The experimental determination of isoelectric point and conductivity in this example 2 is to control the reaction conditions in step e of example 1, and the pH of the reaction system in which the aqueous sodium alginate solution of step a and the mixed emulsion of step d are respectively added dropwise into the heating container is controlled to 5.5.

Example 3 selection experiment of calcium chloride

In step f of example 1 of the present invention, CaCl was added to the reaction system₂The solution is intended to increase the mechanical properties of the final microcapsules and the experimental procedure chosen is as follows.

1、CaCl₂Effect on sodium alginate gel

The gel is prepared by respectively reacting 4% sodium alginate solution with deionized water and 0.3604mol/L calcium chloride, zinc chloride and magnesium chloride solution for 30min at the pH of 7.0 and the temperature of 50 ℃, and the experimental results of the maximum stretching length, the dehydration rate and the elastic recovery time are shown in Table 1.

TABLE 1 influence of coagulant species on gels

Coagulant type (%)	Deionized water	Calcium chloride	Zinc chloride	Magnesium chloride
					Maximum tensile Length (cm)	0.2	1.5	0.5	0.3
Dehydration Rate (%)	97.8	95.8	89.2	95.2
					Elastic recovery time(s)	5.0s	4.5s	4.8s	5.2s

It is seen from table 1 that the calcium chloride solution at the same concentration has a better performance advantage than the gel prepared by reacting the zinc chloride and magnesium chloride solutions with the 4% sodium alginate solution for 30 min. The tensile strength and the dehydration performance of the calcium alginate gel are higher than those of the zinc alginate gel and the magnesium alginate gel, and the elasticity of the four gels is close to that of the zinc alginate gel, probably because the elasticity of the gel is mainly related to the concentration of the sodium alginate.

2. Effect of calcium chloride dosage on sodium alginate gel

The experimental results of the maximum stretching length, dehydration rate and elastic recovery time of the gel prepared by respectively reacting the sodium alginate solution with deionized water and calcium chloride solutions of 0.1802mol/L, 0.3604mol/L and 0.5405mol/L for 30min at the pH of 7.0 and the temperature of 50 ℃ are shown in Table 2.

Table 2 effect of calcium chloride dosage on gelation process

Calcium chloride concentration (%)	0	0.1802mol/L	0.3604mol/L	0.5405mol/L
					Maximum tensile Length (cm)	0.2cm	0.5cm	1.5cm	1.2cm
DewateringPercentage (%)	97.8％	94.8％	89.2％	90.6％
					Elastic recovery time(s)	5.0s	4.8s	4.5s	4.5s

As seen from Table 2, the gel prepared by reacting 0.3604mol/L calcium chloride solution with 4% sodium alginate solution for 30min has better tensile strength and dehydration property. The tensile strength and the dehydration property of the calcium alginate gel increase gradually and gradually with the increase of the concentration of the reaction calcium chloride, and the reason is that the Ca content is 0.3604mol/L²⁺Replace Na in sodium alginate⁺Saturation is reached, calcium chloride concentration continues to increase, and no Na is left in the calcium alginate gel⁺Is substituted. Therefore, the concentration of calcium chloride is preferably controlled to be 0.3 to 0.4 mol/L.

4. Effect of reaction temperature on sodium alginate gel

The results of the maximum stretching length, dehydration rate and elastic recovery time of the gel prepared by reacting a 2.0% sodium alginate solution and 0.3604mol/L calcium chloride solution at pH 7.0 for 30min at different temperatures are shown in Table 3.

TABLE 3 temperature influence on the gelling Process

As can be seen from Table 4, as the gel reaction temperature increases, the tensile properties, water absorption and elasticity of the prepared calcium alginate increase and then decrease, and the properties are best at 50 ℃. The reason is that the winding degree of the sodium alginate molecular chain is reduced along with the increase of the reaction temperature, and the sodium alginate molecular chain is in an unfolding state, Ca²⁺Easy to replace Na⁺Forming a network structure, thereby improving the gel performance in the range of 20-50 ℃. The temperature is continuously increased, the G section and the M section of the sodium alginate are more active, the formed chain segment becomes loose, the elasticity is reduced, and Ca²⁺Substituted Na⁺The resulting film is difficult to form a network structure and to retain water, and therefore, the tensile properties and the water-removing properties are deteriorated.

The influence of the temperature on the synthesis of the sodium alginate/chitosan gel is most obvious, the condensation degree is low when the temperature is lower than 40 ℃, the synthesized gel is less, and the stability is poor. The coagulation degree is increased when the temperature is higher than 40 ℃, the synthesized gel is increased, the stability is good, the gel synthesized at 50 ℃ is most saturated, wrinkles can be clearly seen, and the gel begins to be resolved when the temperature is higher than 50 ℃, because the coagulation reaction of chitosan and sodium alginate is damaged by high temperature, and in addition, if the temperature is continuously increased, the molecular chains of sodium alginate and chitosan are easy to break. Therefore, the bath temperature is preferably 50 ℃.

Example 3 gradient structure diagram

Fig. 4 is a schematic structural diagram of a microcapsule prepared according to embodiment 1 of the present invention, in which the capsule wall of the microcapsule is of a strength gradient structure, that is, the shell has a high strength, the internal strength is reduced, and the microcapsule has high strength, toughness and elasticity, so that the microcapsule is beneficial to maintaining good appearance and stability, preventing the leakage of the capsule core substance, effectively protecting the capsule core, slowly releasing the capsule core, and prolonging the efficacy of the capsule core.

Example 3 thermogravimetric analysis (TG)

Each of chitosan, sodium alginate, and the microcapsule prepared in example 1 weighed 6mg of a sample, analyzed with a TG thermal analyzer, and the temperature was raised from room temperature to 600 ℃ at a rate of 10 ℃/min, with the atmosphere being nitrogen. The obtained thermal decomposition temperatures of chitosan, sodium alginate and the microcapsule of example 1 are shown in table 1, and the thermal decomposition temperatures of chitosan, sodium alginate and the microcapsule TG prepared in example 1 are shown in FIG. 4.

TABLE 1 thermal decomposition temperatures of gelatin, sodium alginate and the microcapsules of example 1

As can be seen from Table 1, the thermal decomposition stability temperature of the chitosan/sodium alginate microcapsule prepared by using glutaraldehyde and calcium chloride as cross-linking agents is 267 ℃ which is higher than that of chitosan and sodium alginate, which indicates that the thermal stability of chitosan and sodium alginate is improved by the cross-linking of glutaraldehyde and calcium chloride.

From table 1 it can be seen that the thermal stability of the microcapsules of example 1 passed through is lower than that of chitosan but higher than that of sodium alginate, because calcium chloride reacts with sodium alginate to form calcium alginate, which decomposes at lower temperatures to form CaCO3, and CaCO3 is further oxidized to form CaO and ca (oh)2, thus starting to decompose at lower temperatures than chitosan.

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be able to cover the technical scope of the present invention, the technical solutions and the inventive concepts of the present invention with equivalent or modified alternatives and modifications within the technical scope of the present invention.

Claims

1. A microcapsule with a gradient capsule wall structure comprises a wall material and an oily capsule core substance, and is characterized in that the wall material is a polymer formed by crosslinking chitosan/sodium alginate with glutaraldehyde, and the chemical structural formula of the polymer is shown as a formula (I):

2. a preparation method of microcapsules with a gradient wall structure specifically comprises the following steps:

h. and g, adding excessive glutaraldehyde aqueous solution into the reaction system in the step g, and completely reacting to obtain the microcapsule with the gradient capsule wall structure.

3. The method for preparing microcapsules with a gradient wall structure according to claim 3, wherein the oily core material is one or more of corn oil, olive oil, soybean oil, fish oil, oily essence and oily probiotics.

4. The process for the preparation of microcapsules with a gradient wall structure according to claim 3, wherein said step c comprises in particular: stirring the sucrose fatty acid ester and the oily cystic substance at the temperature of 25-30 ℃ and the rpm of 800 for 5-10 min.

5. The process for preparing microcapsules having a gradient wall structure according to claim 3, wherein said step d comprises: the emulsification temperature is 25-30 ℃, the emulsification time is 30min, and the stirring speed is 600-800 rpm.

6. A process for the preparation of microcapsules with a gradient wall structure according to claim 2, characterized in that: the step f specifically comprises the following steps: and (b) dropwise adding the sodium alginate aqueous solution obtained in the step (a) into the mixed emulsion obtained in the step (e) under stirring at the temperature of 25-30 ℃, controlling the dropwise adding speed to be 1mL/min, controlling the stirring speed to be 800rpm, adjusting the pH value to be 5.5, and reacting for 60 min.

7. A process for the preparation of microcapsules with a gradient wall structure according to claim 2, characterized in that: and g, controlling the concentration of the calcium chloride solution in the step g to be 0.3-0.4mol/L, controlling the dropping speed of the calcium chloride solution to be 1mL/min, stopping dropping when insoluble substances appear in the solution, and carrying out curing reaction at 50 ℃ for 30 min.

8. The method for preparing microcapsules with a gradient wall structure according to claim 2, wherein the mass fraction of the glutaraldehyde solution in step h is 25%.

9. The method for preparing microcapsules with a gradient wall structure according to claim 2, wherein the step h is followed by adding deionized water to the reaction system, performing suction filtration, and washing to remove unreacted glutaraldehyde, thereby obtaining microcapsules with a gradient wall structure.

10. The method for preparing microcapsules with a gradient wall structure according to claim 2, wherein the ratio of the components is, calculated by mass fraction: 60-70 parts of sodium alginate, 60-70 parts of chitosan, 8-15 parts of oily capsule core substances, 0.3-0.6 part of sucrose fatty acid ester, 15-30 parts of calcium chloride and 7-10 parts of glutaraldehyde.