Preparation method of chlorogenic acid microcapsule

Abstract

The invention relates to the technical field of biological medicine, in particular to a preparation method of a chlorogenic acid microcapsule. The invention provides a chlorogenic acid microcapsule. The chlorogenic acid microcapsule comprises the following components: a composite wall material, porous starch and chlorogenic acid, the composite wall material is prepared from sodium alginate and chitosan. According to the invention, the chlorogenic acid is wrapped by utilizing the synergistic effect of the porous starch, the chitosan and the sodium alginate, so that the affinity and the wrapping capacity of the chlorogenic acid are enhanced, the embedding rate and the drug loading capacity are improved, no chemical cross-linking agent or organic solvent residue exists, and the safety and the biocompatibility are high.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine, and particularly relates to a preparation method of chlorogenic acid microcapsules. BACKGROUND

[0002] Chlorogenic acid (CGA) is a phenolic acid active ingredient widely existing in natural plants such as honeysuckle, coffee and chrysanthemum, and has various biological activities such as antioxidant, anti-inflammatory, antibacterial and regulation of sugar and lipid metabolism, and has important application value in the fields of medicine, health food and cosmetics. However, the molecular structure of chlorogenic acid contains multiple phenolic hydroxyl groups and ester groups, and has poor chemical stability, is easily affected by temperature, light, pH value and oxidation conditions, is easily degraded under high temperature (above 80 DEG C), strong light or alkaline environment (pH>7.0), and causes loss of activity. At the same time, chlorogenic acid has strong water solubility but poor lipid solubility, has poor dispersibility in oil-based products (such as functional cream and soft capsules), and is easily hydrolyzed by gastrointestinal enzymes after oral administration, and has a bioavailability of only 30% to 40%. In order to solve the above problems, microencapsulation technology is a key means to improve the stability of chlorogenic acid and optimize its application performance. Microencapsulation can realize physical protection, controlled release and solubility adjustment of chlorogenic acid by wrapping chlorogenic acid in a high molecular wall material (such as polysaccharide, protein and lipid) to form a micron-sized particle. At present, there are many mature methods for preparing chlorogenic acid microcapsules, but there are still significant technical bottlenecks.

[0003] The main preparation methods of chlorogenic acid microcapsules include spray drying method, emulsification-crosslinking method, complex coacervation method and solvent evaporation method, and the specific limitations are as follows:

[0004] 1. Spray drying method: this method forms microcapsules by rapidly drying the mixed emulsion of chlorogenic acid and wall material in hot gas after high-pressure atomization, and has the advantages of high efficiency and easy industrialization. However, chlorogenic acid is sensitive to heat (degrades significantly above 80 DEG C), and the inlet air temperature of spray drying is usually as high as 150 to 200 DEG C, resulting in a loss rate of chlorogenic acid activity of more than 30%. At the same time, the wall material (such as gum arabic) is easily hardened on the surface under high temperature, and the microcapsules formed have high porosity, weak barrier protection effect on chlorogenic acid, and are easily broken and the active ingredients are lost at a rate of 20% to 40% during storage (especially when the humidity is greater than 60%).

[0005] 2. Emulsification-Crosslinking Method: This method involves dispersing chlorogenic acid in an emulsion of a wall material (such as gelatin or chitosan), and then adding a chemical crosslinking agent (such as glutaraldehyde or sodium tripolyphosphate) to solidify the wall material into microcapsules. However, chemical crosslinking agents are cytotoxic (e.g., the residual amount of glutaraldehyde must be strictly controlled below 0.1 mg / kg), limiting their application in the food and pharmaceutical industries. Furthermore, the crosslinking reaction must be carried out under acidic or alkaline conditions (pH 3.0–5.0 or 8.0–9.0), and the stability of chlorogenic acid drops sharply in such off-neutral environments, resulting in an encapsulation rate of only 50%–70%.

[0006] 3. Complex Coagulation Method: This method uses gelatin-gum arabic as a typical wall material. By adjusting the pH of the system to the isoelectric point (approximately 4.0), the two polymers undergo charge coagulation, encapsulating chlorogenic acid to form microcapsules. However, this process is extremely sensitive to pH: on the one hand, chlorogenic acid is prone to ester bond hydrolysis at around pH 4.0, leading to premature degradation of chlorogenic acid; on the other hand, the thermal gelation properties of gelatin require insulation conditions of 40–50°C, which still causes some loss of chlorogenic acid activity. The final product's drug loading is usually less than 20%, making it difficult to meet the needs of high-activity applications.

[0007] 4. Solvent Evaporation Method: This method involves dissolving chlorogenic acid and wall materials (such as polylactic acid and ethyl cellulose) in an organic solvent (such as dichloromethane and ethyl acetate), emulsifying the mixture, and then evaporating the solvent to form microcapsules. However, residual organic solvents (even if they meet national standards, they may still exist at 0.01% to 0.1%) can affect product safety, and the solvent recovery process is complex, increasing production costs by more than 30%. Furthermore, hydrophobic wall materials have poor compatibility with water-soluble chlorogenic acid, making chlorogenic acid leakage likely and resulting in insufficient encapsulation stability.

[0008] This invention addresses the problems of severe chlorogenic acid activity loss, low encapsulation rate and stability, insufficient safety, and complex processes in existing methods. Summary of the Invention

[0009] The purpose of this invention is to provide chlorogenic acid microcapsules with high encapsulation efficiency, high safety and biocompatibility, and a method for preparing the same.

[0010] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0011] This invention provides a chlorogenic acid microcapsule, comprising the following components: a composite wall material, porous starch, and chlorogenic acid;

[0012] The mass ratio of the composite wall material to chlorogenic acid is 5 to 10:1;

[0013] The mass ratio of the porous starch to chlorogenic acid is 1:4 to 10.

[0014] Preferably, the composite wall material is sodium alginate and chitosan; the mass ratio of sodium alginate to chitosan is 3 to 5:1.

[0015] The present invention also provides a method for preparing the chlorogenic acid microcapsules, comprising the following steps:

[0016] (1) Mix the chitosan solution and calcium chloride solution, adjust the pH to 4-6 and stir to obtain mixed solution 1;

[0017] (2) Mix porous starch and chlorogenic acid solution to obtain mixed solution 2;

[0018] (3) Mix the mixed solution 2 and the sodium alginate solution to obtain the mixed solution 3;

[0019] (4) Add mixed solution 3 dropwise to mixed solution 1, let stand for 15-25 minutes, and then filter to obtain capsules;

[0020] (5) After washing the capsule particles with water, dry and pulverize them to obtain chlorogenic acid microcapsules.

[0021] Preferably, in step (1), the volume ratio of the chitosan solution to the calcium chloride solution is 0.5–1.5:0.5–1.5; the chitosan solution is prepared by dissolving chitosan in dilute acetic acid; and the calcium chloride solution is prepared by dissolving calcium chloride in water.

[0022] The concentration of the calcium chloride solution is 0.03–0.07 g / mL.

[0023] Preferably, in step (1), the stirring is magnetic stirring, the stirring speed is 300-500 rpm, the stirring time is 5-15 min, and the stirring temperature is 40-60℃.

[0024] Preferably, in step (2), the chlorogenic acid solution is prepared by dissolving chlorogenic acid in anhydrous ethanol-water.

[0025] Preferably, in step (2), the mixing is oscillatory mixing; the mixing time is 8 to 12 minutes.

[0026] Preferably, in step (3), the sodium alginate solution is prepared by dissolving sodium alginate in water.

[0027] Preferably, in step (5), the drying is freeze drying; the drying temperature is -40 to -60°C; the drying pressure is 0.4 to 0.6 mbar; and the drying time is 40 to 56 h.

[0028] Preferably, in step (5), the particle size of the pulverized material is 5 to 200 μM.

[0029] The beneficial effects of this invention are:

[0030] This invention utilizes the synergistic effect of porous starch, chitosan, and sodium alginate (hydrophobic interaction + electrostatic adsorption + hydrogen bonding) to encapsulate chlorogenic acid, thereby enhancing the affinity and encapsulation ability for chlorogenic acid, increasing the encapsulation rate from 50-70% in existing methods to over 80%, and increasing the drug loading from below 20% to 20-30%.

[0031] This invention is prepared by encapsulating chlorogenic acid with food-grade materials (porous starch, chitosan) and natural materials (sodium alginate). It has no chemical cross-linking agents (such as glutaraldehyde) or organic solvent residues, and has high safety and biocompatibility.

[0032] Moreover, the present invention adopts a low-temperature physical curing process (such as self-assembly of composite wall materials based on the synergistic effect of hydrogen bonds and ionic bonds), which avoids the destruction of chlorogenic acid by high temperature (spray drying) or chemical crosslinking agents (emulsion-crosslinking method), thereby increasing the chlorogenic acid activity retention rate to more than 80%. Attached Figure Description

[0033] Figure 1 The standard curve for chlorogenic acid;

[0034] Figure 2 The results show the encapsulation efficiency of chlorogenic acid microcapsules.

[0035] Figure 3 The interaction between the composite wall material ratio and the wall-core ratio;

[0036] Figure 4 The interaction between the composite wall material ratio and the porous starch:chlorogenic acid ratio;

[0037] Figure 5 The interaction between the composite wall material ratio and pH value;

[0038] Figure 6 The interaction between the wall-to-core ratio and porous starch: chlorogenic acid;

[0039] Figure 7 The interaction between the wall-to-core ratio and pH value;

[0040] Figure 8 For porous starch: the interaction between chlorogenic acid and pH value. Detailed Implementation

[0041] This invention provides a chlorogenic acid microcapsule, comprising the following components: a composite wall material, porous starch, and chlorogenic acid;

[0042] The mass ratio of the composite wall material to chlorogenic acid is 5-10:1, preferably 7-8:1, and more preferably 7.5:1;

[0043] The mass ratio of porous starch to chlorogenic acid is 1:4 to 10, preferably 1:5 to 9, and more preferably 1:7.

[0044] In this invention, the composite wall material is sodium alginate and chitosan; the mass ratio of sodium alginate to chitosan is 3-5:1, preferably 3.5-4.5:1, and more preferably 4:1.

[0045] The present invention also provides a method for preparing the chlorogenic acid microcapsules, comprising the following steps:

[0046] (1) Mix the chitosan solution and calcium chloride solution, adjust the pH to 4-6 and stir to obtain mixed solution 1;

[0047] (2) Mix porous starch and chlorogenic acid solution to obtain mixed solution 2;

[0048] (3) Mix the mixed solution 2 and the sodium alginate solution to obtain the mixed solution 3;

[0049] (4) Add mixed solution 3 dropwise to mixed solution 1, let stand for 15-25 minutes, and then filter to obtain capsules;

[0050] (5) After washing the capsule particles with water, dry and pulverize them to obtain chlorogenic acid microcapsules.

[0051] In this invention, in step (1), the volume ratio of the chitosan solution and the calcium chloride solution is 0.5-1.5:0.5-1.5, preferably 1:1; the chitosan solution is prepared by dissolving chitosan in dilute acetic acid; the calcium chloride solution is prepared by dissolving calcium chloride in water.

[0052] The concentration of the calcium chloride solution is 0.03–0.07 g / mL, preferably 0.04–0.06 g / mL, and more preferably 0.05 g / mL.

[0053] The stirring is magnetic stirring, the stirring speed is 300-500 rpm, preferably 250-450 rpm, and more preferably 400 rpm; the stirring time is 5-15 min, preferably 8-12 min, and more preferably 10 min; the stirring temperature is 40-60℃, preferably 45-55℃, and more preferably 50℃.

[0054] The pH is preferably 4.5 to 5.5, and more preferably 5.

[0055] In this invention, in step (2), the chlorogenic acid solution is prepared by dissolving chlorogenic acid in anhydrous ethanol;

[0056] The mixing is an oscillating mixing; the mixing time is 8 to 12 minutes, preferably 9 to 11 minutes, and more preferably 10 minutes.

[0057] In this invention, in step (3), the sodium alginate solution is prepared by dissolving sodium alginate in water; the mixing is a stirring mixture.

[0058] In this invention, the specific method of dripping in step (4) is as follows: using a needle to drip the mixed solution 3 into the mixed solution 1 at a uniform speed and stirring slowly; the standing time is preferably 18 to 22 minutes, and more preferably 20 minutes.

[0059] In this invention, in step (5), the drying is freeze drying; the drying temperature is -40 to -60°C, preferably -45 to -55°C, and more preferably -50°C; the drying pressure is 0.4 to 0.6 mbar, preferably 0.5 mbar; and the drying time is 40 to 56 h, preferably 44 to 52 h, and more preferably 48 h.

[0060] In this invention, in step (5), the particle size of the pulverized material is 5 to 200 μM, preferably 55 to 150 μM, and more preferably 102.5 μM.

[0061] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0062] Example 1: A method for preparing chlorogenic acid microcapsules

[0063] Chitosan solution: Dissolve chitosan in 50 mL of dilute acetic acid;

[0064] Calcium chloride solution: Dissolve calcium chloride in water to prepare a calcium chloride solution with a concentration of 0.05 g / mL;

[0065] Chlorogenic acid solution: Dissolve chlorogenic acid in 10 mL of anhydrous ethanol;

[0066] Sodium alginate solution: Dissolve sodium alginate in 30 mL of water;

[0067] (1) Mix chitosan solution and calcium chloride solution at a volume ratio of 1:1, adjust the pH, and then magnetically stir at 50℃ and 400rpm for 10min to obtain mixed solution 1.

[0068] (2) Porous starch was added to chlorogenic acid solution and shaken to mix and adsorb at room temperature for 10 min to obtain mixed solution 2;

[0069] (3) Add sodium alginate solution to mixed solution 2 and stir to mix evenly to obtain mixed solution 3;

[0070] (4) Use a needle to drip mixed solution 3 into mixed solution 1 at a uniform rate, stir slowly, let stand for 20 minutes and then filter to obtain capsules;

[0071] (5) The capsule particles were washed with water and then freeze-dried at -50℃ and 0.5mbar for 48h. After the freeze-drying was completed, the particles were pulverized to a particle size of 100μM to obtain chlorogenic acid microcapsules.

[0072] Example 2: A method for preparing chlorogenic acid microcapsules

[0073] Referring to Example 1, the mass ratio of composite wall material to chlorogenic acid was set to 7.5:1; the mass ratio of porous starch to chlorogenic acid was 1:4; the pH was 6; and the mass ratios of sodium alginate to chitosan were 1:1, 2:1, 3:1, 4:1, and 5:1, respectively.

[0074] Example 3: A method for preparing chlorogenic acid microcapsules

[0075] Referring to Example 1, the mass ratio of sodium alginate to chitosan was set to 3:1; the mass ratio of porous starch to chlorogenic acid was 1:4; the pH was 6; and the mass ratios of composite wall material to chlorogenic acid were 2.5:1, 5:1, 7.5:1, 10:1, 12.5:1, and 15:1, respectively.

[0076] Example 4: A method for preparing chlorogenic acid microcapsules

[0077] Referring to Example 1, the mass ratio of sodium alginate to chitosan was set to 3:1; the mass ratio of composite wall material to chlorogenic acid was 7.5:1; the pH was 6; and the mass ratios of porous starch to chlorogenic acid were 1:3, 1:4, 1:5, 1:10, and 1:20, respectively.

[0078] Example 5: A method for preparing chlorogenic acid microcapsules

[0079] Referring to Example 1, the mass ratio of sodium alginate to chitosan was set to 3:1; the mass ratio of composite wall material to chlorogenic acid was 7.5:1; the mass ratio of porous starch to chlorogenic acid was 1:4; and the pH values ​​were 2, 3, 4, 5, and 6, respectively.

[0080] Experiment Example 1: Construction of the standard curve of chlorogenic acid under ELISA reader detection

[0081] Accurately weigh 10 mg of chlorogenic acid standard and dilute to 100 mL in a volumetric flask with anhydrous ethanol to prepare a 100 μg / mL chlorogenic acid stock solution. Pipette 33.3, 20.0, 16.7, 10.0, 8.3, and 6.7 mL of the stock solution and dilute to 100 mL to prepare chlorogenic acid standard solutions of the following concentrations: 3, 5, 6, 10, 12, and 15 μg / mL. Anhydrous ethanol was used as the blank. The chlorogenic acid concentration and corresponding absorbance were measured at 327 nm using a UV spectrophotometer. Linear regression analysis was performed with absorbance (A) as the ordinate and chlorogenic acid concentration (μg / mL) as the abscissa, yielding the regression equation y = 0.04597x - 0.02222 (R²). 2 =0.9984), the standard curve is as follows Figure 1 As shown.

[0082] The results showed that CGA exhibited a good linear relationship in the range of 3–15 μg / mL at a wavelength of 372 nm.

[0083] Experiment Example 2: Determination of Embedding Rate

[0084] Total chlorogenic acid content of microcapsules: Weigh 0.01g of chlorogenic acid microcapsules, crush them, add 1mL of distilled water and grind for 5min, then sonicate for 10min to dissolve the chlorogenic acid microcapsule wall material. Centrifuge at 12000rpm, 4℃ for 20min and discard the supernatant. Add 1mL of anhydrous ethanol to the precipitate, sonicate for 10min, centrifuge at 12000rpm, 4℃ for 20min and collect the supernatant. Filter the supernatant through a 0.45μm filter membrane, dilute it to a certain proportion, and detect the absorbance of chlorogenic acid at 425nm using an enzyme-linked immunosorbent assay (ELISA) reader. Then determine its content using the standard curve of chlorogenic acid.

[0085] Content of chlorogenic acid on the surface of microcapsules: Weigh 0.01g of chlorogenic acid microcapsules, crush them, add 1mL of anhydrous ethanol, grind for 5min, then sonicate for 10min to fully dissolve the chlorogenic acid on the surface. Centrifuge at 12000rpm, 4℃ for 20min, collect the supernatant, and measure the absorbance at 425nm using an enzyme-linked immunosorbent assay (ELISA) reader. Calculate the encapsulation efficiency according to the following formula:

[0086] Encapsulation efficiency (%) = [(A1-A2) / A1] × 100%, where: A1 is the total chlorogenic acid content in the microcapsules; A2 is the chlorogenic acid content on the surface of the microcapsules;

[0087] The encapsulation efficiency of the chlorogenic acid microcapsules prepared by the methods described in Examples 2-5 was determined according to the above method, and the results are as follows: Figure 2 As shown, where Figure 2 a represents the encapsulation efficiency of the chlorogenic acid microcapsules prepared by the method described in Example 2. Figure 2 b represents the encapsulation efficiency of the chlorogenic acid microcapsules prepared by the method described in Example 3. Figure 2c represents the encapsulation efficiency of the chlorogenic acid microcapsules prepared by the method described in Example 4. Figure 2 d represents the encapsulation efficiency of the chlorogenic acid microcapsules prepared by the method described in Example 5;

[0088] The mass ratio of sodium alginate to chitosan ( Figure 2 a) It can be seen that the encapsulation efficiency first increases and then tends to level off as the proportion of sodium alginate increases; when the mass ratio of composite wall material (sodium alginate: chitosan) is 3:1, the encapsulation efficiency reaches 91.8%; when the composite wall material ratio is lower than 3:1, it may be due to the low concentration of sodium alginate, the low viscosity of the solution, the soft texture of the formed microcapsules, the high fluidity, and the easy breakage; therefore, the subsequent response surface methodology selected composite wall material mass ratios of 3:1, 4:1, and 5:1 as experimental levels.

[0089] The mass ratio of composite wall material to chlorogenic acid ( Figure 2 (b) It can be seen that the encapsulation efficiency first increases and then decreases with the increase of the mass ratio of composite wall material and chlorogenic acid. When the mass ratio of composite wall material to chlorogenic acid is 7.5:1, the maximum encapsulation efficiency is 87.6%. When the chlorogenic acid ratio is lower than 7.5:1, the increased proportion of chlorogenic acid will cause some chlorogenic acid to be embedded in the wall material. When the mass ratio of composite wall material to chlorogenic acid exceeds 7.5:1, the chlorogenic acid content is low, which will cause some composite wall material and blank microcapsules to be generated, resulting in a decrease in the encapsulation efficiency. Considering the above, the mass ratios of composite wall material to chlorogenic acid of 5:1, 7.5:1, and 10:1 are selected as subsequent response levels.

[0090] The mass ratio of porous starch to chlorogenic acid ( Figure 2 c) It can be seen that the encapsulation efficiency first increases and then decreases with the decrease of porous starch content, and can reach a maximum of 86%. If the porous starch content is too high, the solid content will increase, making it difficult for chlorogenic acid to be uniformly mixed with the wall material. When the porous starch content is too low, the solid content will decrease, which will lead to an increase in microcapsule pores and insufficient encapsulation of chlorogenic acid, resulting in a decrease in encapsulation efficiency. Therefore, the mass ratios of 1:4, 1:5, and 1:10 were selected for subsequent response surface level analysis.

[0091] From pH value ( Figure 3-8 d) It can be seen that the encapsulation rate initially increases and then plateauses, with encapsulation rates of 81.5%, 80.8%, and 82.2% at pH values ​​of 4, 5, and 6, respectively. The release of chlorogenic acid from microcapsules made of alginate is pH-dependent. Sodium alginate is a poorly soluble weak acid, with precipitation at pH values ​​below 3.6 and dissolution at pH values ​​of 5.8. When the pH value is low, sodium alginate precipitates, leading to a decrease in the encapsulation rate. Therefore, pH values ​​of 4, 5, and 6 were selected as response surface levels for subsequent experiments.

[0092] Experiment Example 3: Response Surface Experiment

[0093] Based on Experiment 2, four factors affecting microcapsule preparation were selected: the mass ratio of composite wall material to chlorogenic acid (wall-to-core ratio), the mass ratio of sodium alginate to chitosan (composite wall material ratio), the mass ratio of porous starch to chlorogenic acid (porous starch:chlorogenic acid), and pH value. The encapsulation efficiency and drug loading of the prepared chlorogenic acid microcapsules were calculated. Then, Designexpert 13 was used to design a four-factor, three-level response surface methodology with the chlorogenic acid microcapsule encapsulation efficiency as the response value index to optimize the chlorogenic acid microcapsules. The experimental design and the calculation results of the chlorogenic acid microcapsule encapsulation efficiency and drug loading are shown in Table 1. Then, the interaction between the four factors (such as...) were analyzed. Figure 3-8 As shown in Table 2, the regression equation for the response surface model is established as: R = 98.2 + 0.3767*A + 0.4363*B + 0.03*C + 1.24*D + 0.4177*AB. The results of the analysis of variance for the response surface regression model are shown in Table 2.

[0094] The encapsulation efficiency of chlorogenic acid microcapsules was calculated with reference to Experimental Example 2, and the formula for calculating drug loading was as follows:

[0095] The formula for calculating the drug loading of chlorogenic acid microcapsules is: m(%) = (m1 / m2) × 100%, where: m is the drug loading of chlorogenic acid microcapsules; m1 is the total chlorogenic acid content in the microcapsules; and m2 is the mass of the chlorogenic acid microcapsule sample.

[0096] Table 1 Response Surface Design

[0097]

[0098]

[0099] Table 2. Analysis of variance of the regression equations

[0100]

[0101] Note: *p<0.05, **p<0.01; R 2 =0.9658; R 2 Adj = 0.9316

[0102] As shown in Table 2, the response surface model has a p < 0.0001, indicating that the regression model is highly significant and statistically significant, with a correlation coefficient R0. 2 =0.9658, indicating that 96.58% of the values ​​in the response surface central model originate from the four selected influencing factors. The model has a good fit, and the data obtained from the quadratic regression optimization model used shows a high degree of agreement with the actual data; the corrected coefficient of determination R0 2Adj = 0.9316, and this model can be used to predict the theoretical value of the encapsulation rate of chlorogenic acid microcapsules. As can be seen from Table 1, the interaction between the two factors has a significant impact on the encapsulation rate of chlorogenic acid microcapsules, and the encapsulation rate first increases and then decreases with the increase of process parameters. Among them, the F values ​​of composite wall material mass ratio (A), wall-core ratio (B), porous starch:chlorogenic acid (C) and pH value (D) are 1.13, 1.63, 0.81 and 13.11, respectively. From the F values, it can be seen that the influence of each factor on the encapsulation rate of chlorogenic acid microcapsules prepared in this application is D>B>A>C.

[0103] from ​ It can be seen that the encapsulation efficiency of chlorogenic acid microcapsules has a significant interaction relationship with all four factors.

[0104] Therefore, the optimal process conditions predicted by Design-Expert 13 software were A = 4.02, B = 7.62, C = 0.1748, and D = 5.13. These were converted to the optimal embedding conditions of a wall material ratio of 4.02:1, a wall-to-core mass ratio of 7.62:1, a porous starch:chlorogenic acid ratio of 0.1748:1, and a pH of 5.13, resulting in a maximum embedding rate of 98.2924%. Based on actual experimental conditions, the optimal embedding conditions were adjusted as follows: a wall material mass ratio of 4:1, a wall-to-core mass ratio of 7.5:1, a porous starch:chlorogenic acid ratio of 0.175:1, and a pH of 5. Under these conditions, three repeated experiments were conducted to verify an embedding rate of 98.4%. The experimental values ​​and predicted values ​​showed a good fit, indicating that the response surface model is stable and reliable.

[0105] As can be seen from the above embodiments, the present invention provides a method for preparing chlorogenic acid microcapsules. The present invention utilizes the synergistic effect of porous starch, chitosan, and sodium alginate to encapsulate chlorogenic acid, enhancing the affinity and encapsulation ability for chlorogenic acid, improving the encapsulation efficiency and drug loading, and leaving no chemical cross-linking agents or organic solvent residues, resulting in high safety and biocompatibility.

[0106] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A microcapsule of chlorogenic acid, characterized by, The capsule comprises the following components: a composite wall material, porous starch and chlorogenic acid; The mass ratio of the composite wall material and the chlorogenic acid is 5-10:1; The mass ratio of the porous starch and the chlorogenic acid is 1:4-10.

2. The microcapsule of green acid according to claim 1, characterized by, The composite wall material is sodium alginate and chitosan; the mass ratio of the sodium alginate and the chitosan is 3-5:

1.

3. The method for preparing the microcapsule of chlorogenic acid according to claim 1 or 2, characterized in that, The method comprises the following steps: (1) mixing a chitosan solution and a calcium chloride solution, adjusting the pH to 4-6, and stirring to obtain a mixed solution 1; (2) mixing porous starch and a chlorogenic acid solution to obtain a mixed solution 2; (3) mixing the mixed solution 2 and a sodium alginate solution to obtain a mixed solution 3; (4) dropping the mixed solution 3 into the mixed solution 1, standing for 15-25 min, and filtering to obtain capsule particles; (5) washing the capsule particles, drying, and crushing to obtain chlorogenic acid microcapsules.

4. The production method according to claim 3, characterized by, In step (1), the volume ratio of the chitosan solution and the calcium chloride solution is 0.5-1.5:0.5-1.5; the chitosan solution is prepared by dissolving chitosan in dilute acetic acid; and the calcium chloride solution is prepared by dissolving calcium chloride in water. The concentration of the calcium chloride solution is 0.03-0.07 g / mL.

5. The preparation method according to claim 4, characterized in that, In step (1), the stirring is magnetic stirring, the stirring speed is 300-500 rpm, the stirring time is 5-15 min, and the stirring temperature is 40-60℃.

6. The preparation method according to claim 5, characterized in that, In step (2), the chlorogenic acid solution is prepared by dissolving chlorogenic acid in anhydrous ethanol.

7. The production method according to claim 6, wherein In step (2), the mixing is oscillation mixing, and the mixing time is 8-12 min.

8. The production method according to claim 7, characterized by, In step (3), the sodium alginate solution is prepared by dissolving sodium alginate in water.

9. The production method according to claim 8, characterized by, In step (5), the drying is freeze-drying, the drying temperature is -40--60℃, the drying pressure is 0.4-0.6 mbar, and the drying time is 40-56 h.

10. The method of claim 9, wherein, In step (5), the particle size of the crushed product is 5-200 μM.

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