Preparation method and application of biological polysaccharide polymer coated PQQ

Abstract

The invention relates to the technical field of biological medicine materials, and provides a preparation method and application of biological polysaccharide macromolecule polymerization coated PQQ, a polysaccharide macromolecule slow-release skeleton carrier used for coating in the method comprises konjac glucomannan and chitosan, the carrier can form a honeycomb net structure, PQQ can be embedded into the net structure, and the PQQ can be embedded into the honeycomb net structure. The coated PQQ has a slow release function in the intestinal environment, the three-dimensional honeycomb structure can be extended under the intestinal environment condition, the PQQ is slowly released, and more than 90% of the PQQ is released within 8 hours.

Description

1. Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a preparation method and application of biopolysaccharide polymer-coated PQQ. 2. Background Technology

[0002] In the vast field of life sciences, various bioactive substances are constantly being discovered and studied in depth. Among them, pyrroloquinoline quinone (PQQ) has gradually emerged and become one of the focuses of attention. As a new cofactor, PQQ exhibits physiological functions similar to vitamins, which makes it play an indispensable role in life activities. Its existence range is extremely wide, spanning multiple biological categories such as prokaryotes, plants and mammals. In our daily diet, we can get PQQ from many foods, such as fermented soybeans or natto. These traditional fermented foods are rich in PQQ ingredients. In addition, fresh fruits and vegetables such as green peppers, kiwis, parsley, tea, papayas, spinach, and celery are also good sources of PQQ. Even in breast milk, PQQ has a certain content, providing potential support for the growth and development of infants and young children.

[0003] In recent years, PQQ has rapidly gained attention in the fields of nutrition and health, and has become a widely watched nutrient. There are many reasons behind this trend. With the continuous deepening of scientific research, people's understanding of the relationship between nutrients and health has gradually deepened. PQQ's unique chemical structure and physiological functions have aroused great interest among scientific researchers, and new research results continue to reveal its important role in maintaining human health. In my country, important progress has also been made in the research and application of PQQ. In 2022 and 2023, my country successively approved PQQ produced by synthesis and fermentation as a new food raw material. This decision not only reflects my country's attention and active exploration of emerging nutrients, but also paves the way for the widespread application of PQQ in the food industry and nutritional supplements.

[0004] From a biochemical point of view, the key reason why PQQ has important physiological significance is that it acts as a coenzyme factor required by a variety of enzymes. Mitochondria carry many key redox reactions, and PQQ actively participates in them. Its main biological functions focus on two core aspects. First, PQQ plays a key supporting role in the growth and development of mitochondria. The normal function and number of mitochondria are essential for the energy supply and overall metabolic balance of cells. PQQ can stimulate the biosynthesis of mitochondria, increase their number and function, and thus provide cells with more abundant energy. This energy boost further promotes the rapid growth and repair of human cells, and has a profound impact on tissue regeneration, wound healing, and the normal development and maintenance of the body. Secondly, PQQ's excellent antioxidant properties are another important physiological feature. In the human body, metabolism is a continuous process, and various factors in the external environment, such as radiation, pollution, and poor diet, will cause a large number of free radicals in the body. These free radicals are highly reactive. If they are not removed in a timely and effective manner, they will cause oxidative damage to various components of the cell, including proteins, lipids, nucleic acids, etc., and then cause cell dysfunction, aging, and even death. With its powerful antioxidant capacity, PQQ can effectively neutralize these free radicals, reduce the damage of oxidative stress to cells, and protect the structural and functional integrity of cells. These two functions make PQQ show a significant effect in many health fields. In terms of brain health, the brain, as one of the most complex and important organs in the human body, has a very high demand for energy and antioxidant protection. PQQ helps maintain the normal metabolism and function of nerve cells by supporting mitochondrial function and scavenging free radicals, thereby improving cognitive ability, enhancing memory, and has a potential protective effect in preventing neurodegenerative diseases such as Alzheimer's disease.

[0005] For the cardiovascular system, the role of PQQ is also not to be underestimated. Cardiovascular disease is one of the major health challenges facing today's society, and its occurrence and development are closely related to oxidative stress and endothelial dysfunction. PQQ can inhibit the oxidative modification of low-density lipoprotein and reduce the formation of foam cells, thereby slowing down the progression of atherosclerosis. At the same time, it can also reduce the inflammatory response of the vascular endothelium, improve the vasodilation function, lower blood pressure, and maintain the health of the cardiovascular system in an all-round way. In terms of metabolic function, PQQ's regulation of insulin sensitivity and promotion of glucose metabolism make it potentially valuable in the prevention and management of metabolic diseases such as diabetes. It helps to optimize the uptake and utilization of glucose by cells, maintain blood sugar stability, and prevent metabolic disorders. However, despite PQQ's significant physiological functions and health benefits, the human body cannot synthesize PQQ itself, which makes external intake the only way to meet the body's needs. When we take PQQ through diet or supplements, due to its highly water-soluble characteristics, the metabolic process in the body exhibits unique kinetic characteristics. After the human body ingests PQQ, it can be quickly absorbed and enter the blood circulation, usually reaching the highest plasma level in about 2 hours. But then, PQQ will be metabolized and eliminated relatively quickly, and the PQQ concentration in plasma will drop to the baseline level after about 8 hours. This rapid absorption and elimination pattern limits the sustained effect and overall bioavailability of PQQ on the human body to a certain extent.

[0006] In summary, in order to give full play to the health-promoting effect of PQQ, the development and research of sustained-release technology to prolong the residence time of PQQ in the human body, so that it can be continuously released and exert its effect over a longer period of time, thereby improving its bioavailability and achieving more ideal biological treatment and prevention effects, has important practical significance and broad market prospects. III. Summary of the invention

[0007] In order to solve the above technical problems, the present invention provides a method for preparing the biopolymer microspheres containing PQQ, which comprises the following steps:

[0008] S1, grinding the modified konjac glucomannan, deacetylated chitosan and trehalose with a colloid mill, and performing physical cross-linking to obtain a biopolymer carrier;

[0009] S2, grinding the PQQ raw material and passing it through an 80 sieve to obtain PQQ;

[0010] S3, mixing and stirring the PQQ and the biopolymer carrier, and wet granulating to obtain stable biopolymer microspheres containing PQQ;

[0011] S4, fluidizing the PQQ-containing high molecular weight polysaccharide microspheres with coating agents selected from the group consisting of hydroxypropyl methylcellulose phthalate (HPMCP), polyvinyl phthalate (PVAP), cellulose acetate trimellitate (CAT), acrylic resin EuS100, Eu1100, and shellac;

[0012] S5. Mix the biopolymer microspheres described in S4 with PQQ to obtain biopolymer mixed microspheres containing PQQ.

[0013] Preferably, the pharmaceutical preparation is selected from one of tablets, capsules, granules and pills;

[0014] On the other hand, the present invention also provides a biopolymer microsphere containing PQQ, the surface of the microsphere is covered with an enteric coating agent.

[0015] Preferably, the biopolymer carrier presents a three-dimensional network structure, and the average particle size of the biopolymer carrier is 500-1000 nm.

[0016] Preferably, the biopolymer carrier is modified konjac glucomannan or deacetylated chitosan with a molecular weight of 5000-10000 Daltons.

[0017] Preferably, the biopolymer microspheres include 50 to 70 parts of biopolymer carriers by weight.

[0018] Preferably, the surface is fluidized-coated, and the coating agent is one or a combination of hydroxypropyl methylcellulose phthalate (HPMCP), polyvinyl phthalate (PVAP), cellulose acetate trimellitate (CAT), acrylic resin EuS100, Eu1100, and shellac.

[0019] As a preferred method, electrospinning technology is innovatively used to prepare biopolymer carriers to form a unique three-dimensional pore structure, which is beneficial to the loading and sustained release of active ingredients.

[0020] Preferably, the active ingredient is loaded by an impregnation method, which ensures uniform distribution and efficient adsorption of the active ingredient in the carrier.

[0021] Preferably, the freeze-drying process effectively maintains the structural integrity of the formulation and the stability of the active ingredient.

[0022] Preferably, the plasma surface treatment technology enhances the compatibility of the preparation in vivo and further improves its bioavailability.

[0023] On the other hand, the present invention also provides the use of the polysaccharide biopolymer coated PQQ prepared by the preparation process in the preparation of human health care drugs or functional foods.

[0024] On the other hand, the present invention also provides a polysaccharide biopolymer-coated PQQ comprising an effective dose obtained by the preparation process.

[0025] On the other hand, the present invention also provides a functional food, comprising an effective dose of polysaccharide biopolymer-coated PQQ prepared by the preparation process.

[0026] On the other hand, the present invention also provides a novel sustained-release preparation, whose active ingredients include but are not limited to a newly discovered compound X (chemical name: 2-(3,4-dihydroxyphenyl)-5-methoxypyrimidin-4-one, chemical formula: C12H10N2O4, hereinafter referred to as X) and a compound Y (chemical name: L-cysteinyl-L-alanyl-L-serine, chemical formula: C9H17N3O4S, hereinafter referred to as Y).

[0027] Beneficial effects of the invention:

[0028] The above technical scheme of the present invention has the following advantages over the prior art: the biopolymer microspheres containing PQQ described in the present invention include a biopolymer carrier and PQQ dispersed on the biopolymer carrier. The surface of the microspheres is fluidized coated and covered with a layer of acid-resistant and enteric materials, which prolongs the retention time of PQQ in the intestine and improves its bioavailability. At the same time, the tiny cavities of the three-dimensional network of the biopolymer carrier increase the stability of product storage. The biopolymer carrier is prepared by innovative electrospinning technology to form a unique three-dimensional pore structure, which is conducive to the loading and sustained release of active ingredients. The active ingredients are loaded by the impregnation method to ensure the uniform distribution and efficient adsorption of the active ingredients in the carrier. The freeze-drying process effectively maintains the structural integrity of the preparation and the stability of the active ingredients. The plasma surface treatment technology enhances the compatibility of the preparation in the body and further improves its bioavailability. 4. Specific implementation methods

[0029] The present invention is described below with reference to specific examples. It will be appreciated by those skilled in the art that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention in any way.

[0030] Embodiment 1:

[0031] A process for preparing the biopolymer microspheres containing PQQ is provided, which comprises the following steps:

[0032] S1. Preparation of physically modified biopolymer carriers: Grind modified konjac glucomannan, modified chitosan and trehalose with a colloid mill to form a honeycomb three-dimensional interpenetrating network structure and aggregate into polymer polysaccharide microspheres with a particle size of 500-1000 nm, which can increase the surface area of ​​the microspheres and facilitate the release and absorption of PQQ.

[0033] S2, grind the PQQ raw materials and sieve,

[0034] S3, mixing the PQQ obtained in step S2 with the biopolymer carrier and stirring them evenly, granulating and drying to obtain biopolymer microsphere granules containing PQQ, wherein the granules are prepared by the following method:

[0035] a. Add granulation excipients to the biopolymer microspheres containing PQQ and stir, wherein the granulation excipients include 8-10 parts of a wetting agent and 6-8 parts of a binder, wherein the wetting agent is preferably propylene glycol or glycerol, and the binder is preferably hydroxypropyl methylcellulose (HPMC) with a mass concentration of 8-12%,

[0036] b. Wet granulation, adjust the mixing speed (80-120rpm / min) and cutting speed (1500-1800rpm / min) of the granulator to form stable high molecular weight polysaccharide microsphere particles containing PQQ;

[0037] c. Vacuum drying of high molecular weight polysaccharide microsphere particles containing PQQ,

[0038] Fluidized bed coating, the high molecular weight polysaccharide microspheres containing PQQ obtained in step S3 are placed at the bottom of the fluidized bed, the coating agent is placed in a spray device at the top or side of the fluidized bed, the cold air entering the fluidized bed is controlled, passed through a medium efficiency and high efficiency air filter, and heated to 37-40° C., the coating agent is sprayed onto the polysaccharide polymer material containing PQQ after atomization, so that the material is aggregated to form 800-1000 nm microspheres, the coating agent is hydroxypropyl methylcellulose phthalate (HPMCP) polyvinyl alcohol phthalate (PVAP), vinegar One or more combinations of cellulose trimellitate (CAT), acrylic resin EuS100, Eu1100, and shellac, preferably 8-12% hydroxypropyl methylcellulose phthalate (HPMCP) by mass, control the cold air entering the fluidized bed, pass through medium-efficiency and high-efficiency air filters, and heat to 37-40° C. The coating agent is sprayed onto the polymer polysaccharide microspheres after atomization, and an acid-resistant material coating is formed on the surface of the 800-1000nm microspheres. The weight of the microspheres increases by 7-8%, and 8% is preferably controlled in this embodiment for 2 hours;

[0039] S4, fluidizing and coating the PQQ-containing high molecular weight polysaccharide microspheres, wherein the coating agent is one or more combinations of hydroxypropyl methylcellulose phthalate (HPMCP), polyvinyl phthalate (PVAP), cellulose acetate trimellitate (CAT), acrylic resin EuS100, Eu1100, and shellac;

[0040] The biopolymer microspheres containing PQQ described in this embodiment are prepared as a pharmaceutical preparation, which can release the PQQ effective ingredient within 6-8 hours after oral administration. In the first 2 hours, the pharmaceutical preparation stays in the gastric juice and releases the effective ingredient, and in the next 4-8 hours, it stays in the small intestine and releases the effective ingredient. The preparation can be used as a nutritional product for preventing and treating sub-health in humans or pets.

[0041] This embodiment also provides a pharmaceutical preparation, which contains an effective dose of biopolymer nanospheres containing PQQ and pharmaceutically acceptable excipients. In this embodiment, the pharmaceutical preparation is a tablet, which is prepared by the following method: granulation is performed by the granulation method described in Example 1, and then the obtained granules are processed by a tablet press. By adjusting the parameters and pressure of the tableting mold, tablets with target diameter, thickness and hardness can be obtained. The granulation method of this embodiment is different from that of Example 1 in that the granulation excipients are different. In this embodiment, the granulation excipients include 20 parts of binder, 2 parts of magnesium stearate, 20 parts of microcrystalline cellulose and 15 parts of carboxymethyl cellulose, wherein the binder is a mixture of a 10% mass concentration of hydroxypropyl methylcellulose solution.

[0042] Embodiment 2:

[0043] Provided is a functional food, comprising an effective dose of the biopolymer microspheres containing PQQ and an appropriate amount of acceptable excipients, wherein the excipients include at least one of sorbitol, collagen peptide, vitamin E, xylitol, and gelatin. Granulation excipients, by weight, include 20 parts of adhesive, 0.5 parts of magnesium stearate and 20 parts of microcrystalline cellulose, 1 part of polyvinyl pyrrolidone, 2 parts of sodium bicarbonate, and 15 parts of wetting agent, wherein the wetting agent is glycerol, and the adhesive is a starch slurry with a mass concentration of 10%. The microcrystalline cellulose in the excipients serves as a filler and disintegrant, and the polyvinyl pyrrolidone plays a role in protecting the drug and dispersing it, which helps to release the functional ingredient PQQ.

[0044] In this embodiment, the preparation is granules, and the granules are prepared by the method described in Example 1, with the difference that the granulation excipients are different. In this embodiment, the granulation excipients, measured by weight, include 6 parts of binder, 8 parts of microcrystalline cellulose, and 10 parts of wetting agent, wherein the wetting agent is pure water, and the binder is modified starch with a mass concentration of 10%.

[0045] The preparation prepared in Example 2 was immersed in a phosphate buffer solution at pH = 7.2 for 10 h, and the release rates of PQQ at 2, 4, 6, 8, and 10 h after storage for 3 months, 6 months, 9 months, 12 months, and 18 months were tested respectively. The test results are shown in Table 1. The storage stability is judged by the PQQ release rate.

[0046] Table 1. Storage stability PQQ release rate evaluation

[0047]

[0048] The tablets prepared in Example 2 were immersed in a simulated gastric acid solution at pH = 2 for 2 h and then immersed in a simulated colon solution at pH = 6.8 for 6 h, and the release rates of PQQ at the 2nd, 4th, 6th, 8th and 10th h were tested respectively. The test results are shown in Table 2: Table 2 The tablets prepared in Example 2 were immersed in a simulated gastric acid solution at pH = 2 for 2 h and then immersed in a simulated colon solution at pH = 6.8 for 6 h, and the release rates of PQQ at the 2nd, 4th, 6th, 8th and 10th h were tested respectively, and the test results.

[0049] Table 2 Evaluation of release rate in simulated colon solution

[0050] Time (hours) Release rate % 0 0 2 17.06 4 28.21 6 32.18 8 13.06 10 5.57 Grand total 96.08

[0051] The tablets prepared in Example 2 were immersed in a simulated colon solution at pH=6.8 for 8 hours, and the release rates of PQQ at 2, 4, 6, 8 and 10 hours were tested respectively. The test results are shown in Table 3.

[0052] Table 3 Evaluation of release rate in simulated colon solution

[0053]

[0054]

[0055] The above test results show that under normal storage conditions, the stability of PQQ in the biopolymer-coated PQQ preparation is not affected; when immersed in simulated gastric acid solution and simulated colon solution, the active ingredient PQQ in the prepared tablet can be slowly released into the solution, and the release of PQQ is not affected. The complex of the present invention can be prepared into a variety of dosage forms.

[0056] Example 3

[0057] Provided is a method for preparing a biopolysaccharide polymer-coated PQQ, which includes adding a new sustained-release preparation, wherein the active ingredients include a newly discovered compound X (chemical name: 2-(3,4-dihydroxyphenyl)-5-methoxypyrimidin-4-one, chemical formula: C12H10N2O4, hereinafter referred to as X) and a compound Y (chemical name: L-cysteinyl-L-alanyl-L-serine, chemical formula: C9H17N3O4S, hereinafter referred to as Y).

[0058] Design principle and group action principle of compound X: In the molecular structure of compound X, the hydroxyl group (-OH) on the benzene ring has a strong electron-donating ability and can effectively capture free radicals through the hydrogen atom transfer mechanism, thereby exerting an antioxidant effect. The methoxy group (-OCH3) increases the stability and lipid solubility of the molecule, which helps it penetrate the cell membrane and be transported and distributed in the body. The nitrogen atom and carbonyl group on the pyrimidine ring can form hydrogen bonds or other non-covalent interactions with enzymes or receptors in the body, thereby regulating the immune response.

[0059] The design principle and group action principle of compound Y: The core structure of compound Y is a tripeptide chain. The sulfhydryl group (-SH) in the L-cysteine ​​residue can form a disulfide bond with other molecules, stabilize the structure of the compound, and promote its accumulation in cells. The hydroxyl (-OH) and carboxyl (-COOH) groups on the L-alanine and L-serine residues increase the water solubility and biocompatibility of the compound, enabling it to better interact with the cellular environment. At the same time, the amino (-NH2) and carboxyl groups in the peptide chain can bind to receptors on the cell surface and initiate signaling pathways for cell regeneration and repair.

[0060] The preparation method comprises the following steps:

[0061] S1. Modified konjac glucomannan (molecular weight 10000-15000) and chitosan derivatives were prepared into nanofiber membranes by electrospinning technology to form biopolymer carriers with three-dimensional pore structures. The specific process parameters were: electrospinning voltage 18 kV, receiving distance 18 cm, solution flow rate 0.8 mL / h.

[0062] S2. Active ingredients X, Y and PQQ are dissolved in a suitable solvent (such as anhydrous ethanol) at a weight ratio of 2:2:1 to prepare a mixed solution, wherein the total concentration of the active ingredients in the solution is 15 mg / mL.

[0063] S3, using the impregnation method to load the mixed solution into the biopolymer carrier, so that the active ingredients fully penetrate and adsorb into the pores of the carrier. The impregnation time is 10 hours and the temperature is 28°C.

[0064] S4. Freeze-drying the carrier loaded with the active ingredient to remove the solvent and obtain a dry sustained-release preparation. The freeze-drying conditions are: temperature -45°C, vacuum degree 15Pa, and time 36 hours.

[0065] S5. The dried preparation is surface modified by using plasma treatment technology to introduce hydrophilic functional groups (such as hydroxyl groups) on the surface of the preparation to improve its compatibility and stability in vivo. The plasma treatment parameters are: power 150W, treatment time 8 minutes, and gas atmosphere argon.

[0066] The sustained-release effect, bioavailability and therapeutic effect of the preparation of the present invention on disease model animals under a simulated in vivo environment were verified.

[0067] 1. Experimental Materials

[0068] Control group preparation: traditional preparation, the active ingredients are the same as those of the preparation of the present invention, but without special sustained-release structure.

[0069] Experimental group preparation: the preparation with sustained-release effect of the present invention.

[0070] Experimental animals: Several healthy adult animals used for bioavailability testing and disease model establishment.

[0071] 2. Experimental Methods

[0072] Active ingredient release monitoring in simulated in vivo environment:

[0073] The control group and experimental group preparations were placed in a device that simulates the in vivo environment, which has temperature, pH value and fluid dynamic conditions similar to the physiological conditions of the human body.

[0074] At regular intervals (such as 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, etc.), samples are collected from the device and the content of the active ingredient is determined by an analytical method such as high performance liquid chromatography.

[0075] Bioavailability Assessment:

[0076] The experimental animals were randomly divided into a control group and an experimental group, with the same number of animals in each group.

[0077] The two groups of animals were given the same dose of the preparation, and blood samples were collected from the animals at different time points after administration (such as 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, etc.).

[0078] The concentration of the active ingredient in blood is measured using a suitable analytical method (such as liquid chromatography-mass spectrometry).

[0079] Observation of therapeutic effects of disease models:

[0080] Disease model animals were established and randomly divided into a control group and an experimental group.

[0081] The two groups of animals were treated with the corresponding preparations, and the disease symptoms (such as weight changes, behavioral performance, etc.) and related physiological indicators (such as blood biochemical indicators, tissue pathological changes, etc.) of the animals were observed.

[0082] 3. Experimental Results and Data Analysis

[0083] Table 4 Release of active ingredients in simulated in vivo environment

[0084]

[0085] It can be seen from the above data that the active ingredients in the control group are released in large quantities in a short period of time, and then the release rate decreases rapidly; while the active ingredients in the experimental group show a continuous and slow release characteristic, maintaining a stable release rate for a long time, proving that the preparation of the present invention has a better sustained-release effect.

[0086] Table 5 Bioavailability evaluation results

[0087]

[0088] By analyzing the changes in the concentration of active ingredients in the blood, it was found that the concentration of active ingredients in the blood of the experimental group animals was maintained within the effective treatment range for a longer period of time, and the bioavailability was significantly higher than that of the control group. This shows that the preparation of the present invention can improve the utilization efficiency of the active ingredients in the body.

[0089] Table 6 Observation results of treatment effects of disease models

[0090]

[0091] Under conditions simulating the in vivo environment, the release of active ingredients in the two groups of preparations was monitored. The results showed that the active ingredients in the control group were released in large quantities in a short period of time, and then the release rate dropped rapidly; while the active ingredients in the experimental group showed a continuous and slow release characteristic, maintaining a stable release rate for a long time, indicating that the preparation of the present invention has a better sustained release effect.

[0092] The same dose of the preparation was given to two groups of animals, and the bioavailability was evaluated by detecting the concentration of the active ingredient in the blood. The results showed that the concentration of the active ingredient in the blood of the experimental group of animals was maintained within the effective treatment range for a longer period of time, and the bioavailability was significantly higher than that of the control group, proving that the preparation of the present invention can improve the utilization efficiency of the active ingredient in the body.

[0093] Disease model animals were established, and the control group and the experimental group were treated with the preparations respectively. The improvement of disease symptoms and changes in related physiological indicators were observed. The results showed that the disease symptoms of the experimental group animals were more significantly improved, and the related physiological indicators recovered faster, indicating that the preparation of the present invention has a better therapeutic effect. The electrospinning technology was innovatively used to prepare biopolymer carriers to form a unique three-dimensional pore structure, which is conducive to the loading and sustained release of active ingredients. The active ingredients were loaded by the impregnation method to ensure the uniform distribution and efficient adsorption of the active ingredients in the carrier. The freeze-drying treatment effectively maintained the structural integrity of the preparation and the stability of the active ingredients. The plasma surface treatment technology enhanced the compatibility of the preparation in the body and further improved its bioavailability.

Claims

1. A method for preparing PQQ coated with biopolysaccharide polymer, characterized in that: The following steps are involved: S1, grinding the modified konjac polysaccharide, chitosan and trehalose with a colloid mill to form high molecular weight polysaccharide microspheres to obtain a biopolymer carrier; S2, grinding the PQQ raw material and sieving to obtain PQQ; S3, mixing and stirring the PQQ, sustained-release agent, and biopolymer carrier, and granulating to obtain biopolymer microspheres containing PQQ; The sustained-release agent is 2-(3,4-dihydroxyphenyl)-5-methoxypyrimidine-4-one and L-cysteinyl-L-alanyl-L-serine.

2. The method for preparing PQQ coated with biopolysaccharide polymer according to claim 1, characterized in that: The granulation method in S3 comprises: a. Add granulation excipients to the biopolymer microspheres containing PQQ and stir, wherein the granulation excipients include 8-10 parts of a wetting agent and 6-8 parts of a binder; b. Wet granulation: adjust the mixing speed and cutting speed of the granulator to form stable high molecular weight polysaccharide microsphere particles containing PQQ.

3. The method for preparing PQQ coated with biopolysaccharide polymer according to claim 1, characterized in that: The mass ratio of 2-(3,4-dihydroxyphenyl)-5-methoxypyrimidin-4-one, L-cysteinyl-L-alanyl-L-serine and PQQ in the granulation method in S3 is 2:2:

1.

4. The method for preparing PQQ coated with biopolysaccharide polymer according to claim 1, characterized in that: The method further comprises: S4. The stable high molecular weight polysaccharide microsphere particles containing PQQ are placed in a fluidized bed coating machine with a double spray device on the top. The cold air entering the fluidized bed is controlled to pass through medium efficiency and high efficiency air filters and then heated. The coating adhesive is atomized by the double spray heads of the fluidized bed and then sprayed onto the polysaccharide polymer material containing PQQ, so that the material is aggregated on its surface to form stable high molecular weight polysaccharide coated microspheres containing PQQ.

5. The method for preparing PQQ coated with biopolysaccharide polymer according to claim 1, characterized in that: According to the operation steps in S1, the biopolymer carrier is konjac glucomannan, and the biopolymer carrier has a three-dimensional network structure.

6. The method for preparing PQQ coated with biopolysaccharide polymer according to claim 1, characterized in that: The method also includes using plasma surface treatment in the S3 operation step to enhance the compatibility of the preparation in vivo and improve its bioavailability.

7. The method for preparing PQQ coated with biopolysaccharide polymer according to claim 1, characterized in that: The step S3 also includes using an impregnation method to load the active ingredient so that it is evenly distributed in the carrier and efficiently adsorbed.

8. The method for preparing PQQ coated with biopolysaccharide polymer according to claim 1, characterized in that: It also includes the step S1 of preparing a biopolymer carrier nanofiber membrane by electrospinning.

9. A polysaccharide biopolymer coated PQQ prepared by the preparation process according to any one of claims 1 to 8, characterized in that: The polysaccharide biopolymer coated PQQ is used in the preparation of human health care medicines or functional foods.

10. A functional food, characterized in that: The invention relates to a polysaccharide biopolymer-coated PQQ comprising an effective dose prepared by the preparation process according to any one of claims 1 to 8.

Images