A resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle and a preparation method thereof

Abstract

The application discloses a resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle which is prepared from the following components and their mass fractions: resveratrol 0.1-1.0 parts, soybean lecithin 5-15 parts, chitosan hydrochloride 0.4-1.2 parts and sodium alginate 0.4-1.2 parts. The application also discloses a preparation method of the resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle. The resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle has obvious slow-release behavior, is beneficial to the absorption of resveratrol in the small intestine of a human body and improves the bioavailability. The preparation method of the resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle is simple and easy to implement, does not need to use organic solvents, has superior light and heat stability and prolongs the storage period of the resveratrol gel microparticle.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical and health care technology, and relates to a resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle and its preparation method. Background Technology

[0002] Resveratrol is a polyphenolic compound, primarily derived from the rhizome extract of the plant Polygonum cuspidatum. It is also abundant in peanut rhizomes and fresh grape skins. Resveratrol possesses numerous physiological functions, including cardiovascular protection and lipid-lowering effects; liver protection and inhibition of lipid peroxide accumulation in the liver; inhibition of cancer cell growth; antibacterial, anti-allergic, anti-inflammatory, and antioxidant effects. It is a rare compound that combines medicinal and nutritional benefits. Therefore, resveratrol has great application potential in multiple fields such as medicine, cosmetics, and food. In recent years, resveratrol has received increasing attention as a nutritional supplement, and a large number of resveratrol-related products have appeared on the market, including chewable tablets, powder capsules, and oil-based soft gels. However, it still suffers from problems such as unsatisfactory light and heat stability, low solubility in digestive juices, and insufficient absorption by the human body.

[0003] Liposomes are spherical vesicles formed by the self-assembly of amphiphilic molecules (usually phospholipid molecules) in an aqueous phase. A liposome consists of one or more bilayers and an inner aqueous phase encapsulated by the bilayer. Liposomes effectively improve the water dispersibility and bioavailability of hydrophobic active ingredients, preventing them from being affected by light, heat, and oxygen. Due to their biocompatibility, low toxicity, and biodegradability, liposomes have been extensively studied in the food industry, primarily for encapsulating unstable compounds such as antioxidants, vitamins, flavorings, and antibacterial agents. While liposomes offer many advantages, they also have disadvantages such as low encapsulation efficiency, poor storage stability, easy oxidation of phospholipids, and short release time.

[0004] There are various methods for preparing liposomes, and the preparation method has a significant impact on the properties of liposomes (such as size, number of membrane layers, and encapsulation efficiency). Currently, commonly used traditional preparation methods mainly include thin-film dispersion, ethanol injection, microfluidics, high-pressure homogenization, and heating. Traditional liposome preparation techniques usually require the use of organic reagents or heating and ultrasound, which are not conducive to application in the food industry. Summary of the Invention

[0005] Purpose of the invention: The purpose of this invention is to overcome the shortcomings of resveratrol liposomes, such as low encapsulation efficiency, poor storage stability, easy oxidation of phospholipids, and short release time, and to provide a resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle and its preparation method.

[0006] Technical solution: The resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticles of the present invention are prepared from the following components and their mass parts as raw materials: 0.1~1.0 parts of resveratrol, 5~15 parts of soybean lecithin, 0.4~1.2 parts of chitosan hydrochloride, and 0.4~1.2 parts of sodium alginate.

[0007] Furthermore, the mass ratio of resveratrol to soybean lecithin is 1:10 to 1:50; the mass ratio of soybean lecithin to chitosan hydrochloride is 1:0.04 to 1:0.08; and the mass ratio of chitosan hydrochloride to sodium alginate is 1:0.5 to 1:1.5.

[0008] Furthermore, a method for preparing resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticles is provided, comprising the following steps:

[0009] (1) Preparation of resveratrol liposomes;

[0010] (2) Prepare a resveratrol liposome-chitosan-alginate emulsion by combining resveratrol liposomes with chitosan hydrochloride and sodium alginate;

[0011] (3) Crosslinking was performed using two ions under high-speed shearing conditions to prepare resveratrol-chitosan-algin polyelectrolyte gel microparticles.

[0012] Further, step (1) includes:

[0013] a. Add soybean lecithin to deionized water and stir at 40-60 ℃ until completely dissolved to obtain mixture A;

[0014] b. Dissolve resveratrol in an alkaline solution and stir to obtain mixture B;

[0015] c. Add mixture A to mixture B, stir, and immediately adjust the pH value with an acidic solution to obtain resveratrol liposomes.

[0016] Furthermore, the pH value is 5.0 to 6.0.

[0017] Further, step (2) includes:

[0018] a. Add chitosan hydrochloride to resveratrol liposomes, stir and dissolve evenly to obtain resveratrol liposome-chitosan emulsion;

[0019] b. Dissolve sodium alginate in deionized water to obtain a sodium alginate solution;

[0020] c. Add the resveratrol liposome-chitosan emulsion to the sodium alginate solution, stir thoroughly, and adjust the pH to 5.0~6.0 to obtain the resveratrol liposome-chitosan-algin emulsion.

[0021] Further, step (3) includes:

[0022] a. Under high-speed shearing conditions, a mixed solution of calcium chloride and barium chloride was gradually added to the resveratrol liposome-chitosan-algin emulsion, and stirring was continued to obtain the sample;

[0023] b. Filter and dry the sample to obtain resveratrol-chitosan-algin polyelectrolyte gel microparticles.

[0024] Furthermore, the molar concentration ratio of the calcium chloride and barium chloride mixed solution is 1:0.5 to 1:2.

[0025] Furthermore, the filtration and drying method in step b is as follows: filter with a 0.22 µm filter membrane, collect solid particles, wash off surface ions with deionized water, and then freeze-dry at -80°C for 24 hours in a freeze dryer.

[0026] Principle: This invention dissolves resveratrol in an alkaline solution, then adds acid to make the pH acidic. This causes resveratrol to change from hydrophilic to hydrophobic. Driven by hydrophobic forces, resveratrol enters the middle of the phospholipid bilayer of the liposome, thus achieving active loading and improving the solubility of resveratrol in aqueous systems. Compared to traditional liposome preparation methods, this method is simple, rapid, leaves no organic solvent residue, and requires no special equipment. Chitosan carries a positive charge in solution and is the only alkaline polysaccharide among natural polysaccharides. Sodium alginate is a natural anionic polysaccharide extracted from brown algae. Under acidic conditions, it exists as a carboxylic acid in a molecular state, while under neutral or alkaline conditions, it exists as a carboxylate in a dissolved state, exhibiting significant pH-responsive behavior, making it an excellent choice for intestinal targeting carrier materials. Utilizing the principle of electrostatic self-assembly, chitosan and sodium alginate are coated onto the surface of the liposomes, improving their stability and achieving enteric release, which is beneficial for the absorption of resveratrol in the human small intestine. When sodium alginate comes into contact with divalent or trivalent cations, it can form a thermally stable hydrogel under mild conditions. Under high shear conditions, it can crosslink to form a network of polyelectrolyte gel microparticles. Liposomes are bound between the gel pores, which can further isolate light and heat and improve the stability of liposomes. At the same time, it can also regulate the release of resveratrol to achieve a sustained-release effect and further improve bioavailability.

[0027] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:

[0028] 1. The resveratrol gel microparticles provided by the present invention have excellent light and heat stability, which extends the storage period of the resveratrol gel microparticles.

[0029] 2. The resveratrol gel microparticles provided by this invention have intestinal targeting behavior and can slow down the digestion and absorption rate of resveratrol, which is beneficial to the absorption of resveratrol in the human small intestine and improves bioavailability.

[0030] 3. The resveratrol gel microparticles provided by the present invention are cross-linked using two ions in a certain ratio. This cross-linking method has higher cross-linking strength and mechanical strength than microparticles obtained by a single ion cross-linking agent. Cross-linking under high shear conditions results in gel microparticles with higher uniformity than other methods.

[0031] 4. The method for preparing liposomes provided by this invention is simple and easy to implement. No organic solvents are required during the preparation process, there is no solvent residue, and no special equipment is needed.

[0032] 5. The resveratrol gel microparticles provided by this invention have high safety and are suitable for use in the pharmaceutical, food and other fields. Attached Figure Description

[0033] Figure 1 The in vitro release curve of the resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticles of the present invention is shown. Detailed Implementation

[0034] The technical solution of the present invention will be further described below with reference to the accompanying drawings.

[0035] The present invention will be further described below through specific embodiments, but this is not a limitation of the present invention. Those skilled in the art can make various modifications or improvements based on the basic idea of ​​the present invention, but as long as they do not depart from the basic idea of ​​the present invention, they are all within the scope of the present invention.

[0036] Example 1: A resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle

[0037] The resveratrol polyelectrolyte gel microparticles comprise the following components and their mass fractions:

[0038] Resveratrol 0.1 parts, soybean lecithin 5 parts, chitosan hydrochloride 0.4 parts, sodium alginate 0.4 parts.

[0039] The preparation method of the resveratrol polyelectrolyte gel microparticles includes the following steps:

[0040] S1 Add 5 parts of soybean lecithin to 100 parts of deionized water and stir at 50 °C until completely dissolved to obtain mixture A;

[0041] S2 dissolves 0.1 parts of resveratrol in 10 parts of 0.1 mol / L NaOH solution and stirs at 1000 rpm for 2 min to obtain mixture B;

[0042] S3 Add mixture A to mixture B, stir at 1000 rpm for 2 min, and immediately adjust the pH to 5.0 with 1 mol / L HCl solution to obtain resveratrol liposomes;

[0043] S4. Add 0.4 parts of chitosan hydrochloride to resveratrol liposomes, stir and dissolve evenly to obtain resveratrol liposome-chitosan emulsion;

[0044] S5 Dissolve 0.4 parts of sodium alginate in 50 parts of deionized water to obtain a sodium alginate solution;

[0045] S6. Add resveratrol liposome-chitosan emulsion to sodium alginate solution, stir at 1000 rpm for 20 min, and adjust the pH to 5.0 with 1 mol / L NaOH or 1 mol / L HCl solution to obtain resveratrol liposome-chitosan-algin emulsion.

[0046] S7 Under high-speed shearing conditions of 8000 rpm, 25 parts of a mixed solution of 0.67 mol / L calcium chloride and 0.33 mol / L barium chloride were added dropwise to the resveratrol liposome-chitosan-alginic acid emulsion. After the addition was completed, the mixture was stirred at 1000 rpm for 20 min.

[0047] S8. Filter the sample from the previous step using a 0.22 µm filter membrane, collect the solid particles, wash off the surface ions with deionized water, and then freeze-dry at -80℃ for 24 hours to obtain resveratrol-chitosan-alginic acid polyelectrolyte gel microparticles.

[0048] Example 2: A resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle

[0049] The resveratrol polyelectrolyte gel microparticles comprise the following components and their mass fractions:

[0050] 1 part resveratrol, 15 parts soybean lecithin, 1.2 parts chitosan hydrochloride, and 1.2 parts sodium alginate.

[0051] The preparation method of the resveratrol polyelectrolyte gel microparticles includes the following steps:

[0052] S1 Add 15 parts of soybean lecithin to 300 parts of deionized water and stir at 50 °C until completely dissolved to obtain mixture A;

[0053] S2 dissolves 1 part resveratrol in 100 parts 0.1 mol / L NaOH solution and stirs at 1000 rpm for 2 min to obtain mixture B;

[0054] S3 Add mixture A to mixture B, stir at 1000 rpm for 2 min, and immediately adjust the pH to 5.0 with 1 mol / L HCl solution to obtain resveratrol liposomes;

[0055] S4. Add 1.2 parts of chitosan hydrochloride to resveratrol liposomes, stir and dissolve evenly to obtain resveratrol liposome-chitosan emulsion;

[0056] S5 Dissolve 1.2 parts of sodium alginate in 150 parts of deionized water to obtain a sodium alginate solution;

[0057] S6. Add resveratrol liposome-chitosan emulsion to sodium alginate solution, stir at 1000 rpm for 20 min, and adjust the pH to 5.0 with 1 mol / L NaOH or 1 mol / L HCl solution to obtain resveratrol liposome-chitosan-algin emulsion.

[0058] S7 Under high-speed shearing conditions of 8000 rpm, 75 parts of a mixed solution of 0.33 mol / L calcium chloride and 0.67 mol / L barium chloride were added dropwise to the resveratrol liposome-chitosan-alginic acid emulsion. After the addition was completed, the mixture was stirred at 1000 rpm for 20 min.

[0059] S8. Filter the sample from the previous step using a 0.22 µm filter membrane, collect the solid particles, wash off the surface ions with deionized water, and then freeze-dry at -80℃ for 24 hours to obtain resveratrol-chitosan-alginic acid polyelectrolyte gel microparticles.

[0060] Example 3: A resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle

[0061] The resveratrol polyelectrolyte gel microparticles comprise the following components and their mass fractions:

[0062] 0.5 parts resveratrol, 10 parts soybean lecithin, 0.8 parts chitosan hydrochloride, and 0.8 parts sodium alginate.

[0063] The preparation method of the resveratrol polyelectrolyte gel microparticles includes the following steps:

[0064] S1 Add 10 parts of soybean lecithin to 200 parts of deionized water and stir at 50 °C until completely dissolved to obtain mixture A;

[0065] S2 dissolves 0.5 parts of resveratrol in 50 parts of 0.1 mol / L NaOH solution and stirs at 1000 rpm for 2 min to obtain mixture B;

[0066] S3 Add mixture A to mixture B, stir at 1000 rpm for 2 min, and immediately adjust the pH to 5.0 with 1 mol / L HCl solution to obtain resveratrol liposomes;

[0067] S4. Add 0.8 parts of chitosan hydrochloride to resveratrol liposomes, stir and dissolve evenly to obtain resveratrol liposome-chitosan emulsion;

[0068] S5 Dissolve 0.8 parts of sodium alginate in 100 parts of deionized water to obtain a sodium alginate solution;

[0069] S6. Add resveratrol liposome-chitosan emulsion to sodium alginate solution, stir at 1000 rpm for 20 min, and adjust the pH to 5.0 with 1 mol / L NaOH or 1 mol / L HCl solution to obtain resveratrol liposome-chitosan-algin emulsion.

[0070] S7 Under high-speed shearing conditions of 8000 rpm, 50 parts of a mixed solution of 0.5 mol / L calcium chloride and 0.5 mol / L barium chloride were added dropwise to the resveratrol liposome-chitosan-alginic acid emulsion. After the addition was completed, the mixture was stirred at 1000 rpm for 20 min.

[0071] S8. Filter the sample from the previous step using a 0.22 µm filter membrane, collect the solid particles, wash off the surface ions with deionized water, and then freeze-dry at -80℃ for 24 hours to obtain resveratrol-chitosan-alginic acid polyelectrolyte gel microparticles.

[0072] Comparative Example 1: A resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle

[0073] The resveratrol polyelectrolyte gel microparticles comprise the following components and their mass fractions:

[0074] 0.5 parts resveratrol, 10 parts soybean lecithin, 0.8 parts chitosan hydrochloride, and 0.8 parts sodium alginate.

[0075] The preparation method of the resveratrol polyelectrolyte gel microparticles includes the following steps:

[0076] S1 Add 10 parts of soybean lecithin to 100 parts of deionized water and stir at 50 °C until completely dissolved to obtain mixture A;

[0077] S2 dissolves 0.5 parts of resveratrol in 50 parts of 0.1 mol / L NaOH solution and stirs at 1000 rpm for 2 min to obtain mixture B;

[0078] S3 Add mixture A to mixture B, stir at 1000 rpm for 2 min, and immediately adjust the pH to 5.0 with 1 mol / L HCl solution to obtain resveratrol liposomes;

[0079] S4. Add 0.8 parts of chitosan hydrochloride to resveratrol liposomes, stir and dissolve evenly to obtain resveratrol liposome-chitosan emulsion;

[0080] S5 Dissolve 0.8 parts of sodium alginate in 100 parts of deionized water to obtain a sodium alginate solution;

[0081] S6. Add resveratrol liposome-chitosan emulsion to sodium alginate solution, stir at 1000 rpm for 20 min, and adjust the pH to 5.0 with 1 mol / L NaOH or 1 mol / L HCl solution to obtain resveratrol liposome-chitosan-algin emulsion.

[0082] S7 Under high-speed shearing conditions of 8000 rpm, 50 parts of 1 mol / L calcium chloride solution were added dropwise to the resveratrol liposome-chitosan-alginic acid emulsion, and stirring was continued at 1000 rpm for 20 min after the addition was completed.

[0083] S8. Filter the sample from the previous step using a 0.22 µm filter membrane, collect the solid particles, wash off the surface ions with deionized water, and then freeze-dry at -80℃ for 24 hours to obtain resveratrol-chitosan-alginic acid polyelectrolyte gel microparticles.

[0084] Comparative Example 2: A resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticle

[0085] The resveratrol polyelectrolyte gel microparticles comprise the following components and their mass fractions:

[0086] 0.5 parts resveratrol, 10 parts soybean lecithin, 0.8 parts chitosan hydrochloride, and 0.8 parts sodium alginate.

[0087] The preparation method of the resveratrol polyelectrolyte gel microparticles includes the following steps:

[0088] S1 Add 10 parts of soybean lecithin to 200 parts of deionized water and stir at 50 °C until completely dissolved to obtain mixture A;

[0089] S2 dissolves 0.5 parts of resveratrol in 50 parts of 0.1 mol / L NaOH solution and stirs at 1000 rpm for 2 min to obtain mixture B;

[0090] S3 Add mixture A to mixture B, stir at 1000 rpm for 2 min, and immediately adjust the pH to 5.0 with 1 mol / L HCl solution to obtain resveratrol liposomes;

[0091] S4. Add 0.8 parts of chitosan hydrochloride to resveratrol liposomes, stir and dissolve evenly to obtain resveratrol liposome-chitosan emulsion;

[0092] S5 Dissolve 0.8 parts of sodium alginate in 100 parts of deionized water to obtain a sodium alginate solution;

[0093] S6. Add resveratrol liposome-chitosan emulsion to sodium alginate solution, stir at 1000 rpm for 20 min, and adjust the pH to 5.0 with 1 mol / L NaOH or 1 mol / L HCl solution to obtain resveratrol liposome-chitosan-algin emulsion.

[0094] S7 Under high-speed shearing conditions of 8000 rpm, 50 parts of 1 mol / L barium chloride solution were added dropwise to resveratrol liposome-chitosan-alginic acid emulsion, and stirring was continued at 1000 rpm for 20 min after the addition was completed.

[0095] S8. Filter the sample from the previous step using a 0.22 µm filter membrane, collect the solid particles, wash off the surface ions with deionized water, and then freeze-dry at -80℃ for 24 hours to obtain resveratrol-chitosan-alginic acid polyelectrolyte gel microparticles.

[0096] Comparative Example 3: A resveratrol liposome-chitosan-alginic acid polyelectrolyte gel particle

[0097] The resveratrol polyelectrolyte gel particles comprise the following components and their mass fractions:

[0098] 0.5 parts resveratrol, 10 parts soybean lecithin, 0.8 parts chitosan hydrochloride, and 0.8 parts sodium alginate.

[0099] The preparation method of the resveratrol polyelectrolyte gel particles includes the following steps:

[0100] S1 Add 10 parts of soybean lecithin to 200 parts of deionized water and stir at 50 °C until completely dissolved to obtain mixture A;

[0101] S2 dissolves 0.5 parts of resveratrol in 50 parts of 0.1 mol / L NaOH solution and stirs at 1000 rpm for 2 min to obtain mixture B;

[0102] S3 Add mixture A to mixture B, stir at 1000 rpm for 2 min, and immediately adjust the pH to 5.0 with 1 mol / L HCl solution to obtain resveratrol liposomes;

[0103] S4. Add 0.8 parts of chitosan hydrochloride to resveratrol liposomes, stir and dissolve evenly to obtain resveratrol liposome-chitosan emulsion;

[0104] S5 Dissolve 0.8 parts of sodium alginate in 100 parts of deionized water to obtain a sodium alginate solution;

[0105] S6. Add resveratrol liposome-chitosan emulsion to sodium alginate solution, stir at 1000 rpm for 20 min, and adjust the pH to 5.0 with 1 mol / L NaOH or 1 mol / L HCl solution to obtain resveratrol liposome-chitosan-algin emulsion.

[0106] S7. Slowly add 50 parts of a mixed solution of 0.5 mol / L calcium chloride and 0.5 mol / L barium chloride to the resveratrol liposome-chitosan-algin emulsion while stirring at 1000 rpm. After the addition is complete, allow it to stand for cross-linking for 20 min.

[0107] S8. Filter the sample from the previous step using a filter cloth, collect the solid particles, wash off the surface ions with deionized water, and then freeze-dry at -80℃ for 24 hours in a freeze dryer to obtain resveratrol-chitosan-alginic acid polyelectrolyte gel particles.

[0108] Experimental Example 1: Photostability of Resveratrol Liposomes-Chitosan-Alginate Polyelectrolyte Gel Microparticles

[0109] Experimental materials: resveratrol gel microparticles prepared in Examples 1, 2, 3, Comparative Examples 1, 2, and 3.

[0110] Experimental method: The sample was placed under natural light at room temperature for four weeks. An appropriate amount of sample was taken every week and the content of resveratrol was detected. The retention rate of resveratrol was calculated.

[0111] Experimental results: The experimental results are shown in Table 1.

[0112] Table 1. Results of photostability test of resveratrol gel particles

[0113]

[0114] As shown in Table 1, the resveratrol gel microparticles prepared in Examples 1, 2, and 3 of this invention exhibit high retention rates under light irradiation. Among them, Example 3 shows the highest retention rate and is the optimal embodiment of this invention. The difference between Comparative Examples 1, 2, and 3 lies in the fact that Comparative Examples 1 and 2 both use a single ionic crosslinking agent. The resveratrol retention rates of Comparative Examples 1 and 2 are lower than those of Example 3, indicating that the gel particle structures formed by the dual ionic crosslinking agents are complementary, resulting in a denser gel particle structure, higher mechanical stability, and stronger protection for resveratrol. Comparative Example 3 uses a crosslinking method different from that of Example 3, where sodium alginate emulsion is slowly added to a large amount of dual ionic solution under low-speed stirring for static crosslinking. The resveratrol retention rate of Comparative Example 3 is lower than that of Example 3, indicating that the gel particles formed by the crosslinking method of this invention have a high degree of crosslinking, high mechanical strength, and strong protection for resveratrol.

[0115] Experimental Example 2: In vitro release of resveratrol liposomes-chitosan-alginic acid polyelectrolyte gel microparticles

[0116] Experimental materials: resveratrol gel microparticles prepared in Examples 1, 2, 3, Comparative Examples 1, 2, and 3.

[0117] Experimental Method: The release characteristics of resveratrol liposomes-chitosan-alginic acid polyelectrolyte gel microparticles were investigated using the dialysis bag method. A certain amount of sample was weighed into a dialysis bag, which was sealed with two dialysis bag clamps to ensure no air bubbles appeared in the bag and no leakage at the seal. The dialysis bag was then placed in 200 mL of release medium. For the first 2 hours of the experiment, a mixture of hydrochloric acid solution (pH = 1.2) and anhydrous ethanol (7:3, v / v) was used as the release medium. After 2 hours, a mixture of phosphate buffer solution (pH = 6.8) and anhydrous ethanol (7:3, v / v) was used. The release medium temperature was maintained at 37℃, and the magnetic stirring speed was 150 rpm. After the experiment began, samples were taken at pre-set time points using a pipette, with each sample being 3 mL. After each sampling, 3 mL of fresh release medium was added to maintain a constant total release medium volume. The resveratrol content in the sample was then detected using a UV spectrophotometer.

[0118] Test results: The test results are as follows Figure 1 As shown.

[0119] Depend on Figure 1It can be seen that the resveratrol gel microparticles prepared in Examples 1, 2, and 3 of this invention hardly release any resveratrol at pH 1.2, but release it at pH 6.8, a simulated intestinal pH condition, exhibiting obvious intestinal targeting behavior. Compared with Comparative Examples 1 and 2, the gel microparticles prepared by the dual ionic crosslinking agent in Example 3 have a more compact structure, higher crosslinking strength, and slower release. Compared with Comparative Example 3, different crosslinking methods also affect the release performance. Static crosslinking is achieved by slowly adding sodium alginate emulsion to the ionic solution under low-speed stirring. The gel particles formed by this crosslinking method have a lower degree of crosslinking and a faster release rate. The in vitro release results show that the resveratrol gel microparticles provided by this invention have obvious intestinal targeting behavior and sustained-release effect, which can further control the release of resveratrol and improve bioavailability.

Claims

1. A method for preparing resveratrol liposomes-chitosan-alginic acid polyelectrolyte gel microparticles, characterized in that, The resveratrol liposome-chitosan-alginic acid polyelectrolyte gel microparticles are prepared from the following components and their mass proportions: 0.1-1.0 parts resveratrol, 5-15 parts soybean lecithin, 0.4-1.2 parts chitosan hydrochloride, and 0.4-1.2 parts sodium alginate; the mass ratio of resveratrol to soybean lecithin is 1:10-1:50; the mass ratio of soybean lecithin to chitosan hydrochloride is 1:0.04-1:0.08; and the mass ratio of chitosan hydrochloride to sodium alginate is 1:0.5-1:1.

5. The preparation method of the resveratrol liposome-chitosan-algin polyelectrolyte gel microparticles includes the following steps: (1) Preparation of resveratrol liposomes; (2) Prepare a resveratrol liposome-chitosan-alginate emulsion by combining resveratrol liposomes with chitosan hydrochloride and sodium alginate; (3) Crosslinking is performed using two ions under high-speed shearing conditions to form a network of polyelectrolyte gel, and resveratrol-chitosan-algin polyelectrolyte gel microparticles are prepared. Step (1) includes: a. Add soybean lecithin to deionized water and stir at 40-60 ℃ until completely dissolved to obtain mixture A; b. Dissolve resveratrol in an alkaline solution and stir to obtain mixture B; c. Add mixture A to mixture B, stir, and immediately adjust the pH value with an acidic solution to a value of 5.0-6.0 to obtain resveratrol liposomes; Step (2) includes: a. Add chitosan hydrochloride to resveratrol liposomes, stir and dissolve evenly to obtain resveratrol liposome-chitosan emulsion; b. Dissolve sodium alginate in deionized water to obtain a sodium alginate solution; c. Add resveratrol liposome-chitosan emulsion to sodium alginate solution, stir thoroughly, and adjust the pH value to 5.0~6.0 to obtain resveratrol liposome-chitosan-algin emulsion; Step (3) includes: a. Under high-speed shearing conditions, a mixed solution of calcium chloride and barium chloride was gradually added to the resveratrol liposome-chitosan-alginic acid emulsion, and stirring was continued to obtain the sample; the molar ratio of the mixed solution of calcium chloride and barium chloride was 1:0.5~1:

2. b. Filter and dry the sample to obtain resveratrol-chitosan-algin polyelectrolyte gel microparticles.

2. The method for preparing resveratrol liposomes-chitosan-alginic acid polyelectrolyte gel microparticles according to claim 1, characterized in that, The filtration and drying method in step b of step (3) is as follows: filter with a 0.22 µm filter membrane, collect solid particles, wash off the surface ions with deionized water, and then freeze dry at -80℃ for 24 hours in a freeze dryer.

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