A Cordyceps militaris and Ganoderma lucidum spore powder composite preparation and application thereof

Abstract

The present invention belongs to the technical field of composite preparations, and is specifically related to a Cordyceps militaris Ganoderma lucidum spore powder composite preparation and its application, and its technical points are as follows: the composite preparation is a microcapsule embedded particle, the outer layer is a polylactic-co-glycolic acid copolymer film, and the inner layer is a composite particle of microcapsule coated Cordyceps militaris extract and microcapsule coated Ganoderma lucidum spore powder; calculated by weight, the composite particle is composed of the following components: 20 to 30 parts of microcapsule coated Cordyceps militaris extract, 30 to 50 parts of microcapsule coated Ganoderma lucidum spore powder and 10 to 15 parts of adjuvant; wherein, the microcapsule coated Cordyceps militaris extract, from outside to inside is: enteric layer and Cordyceps militaris extract; microcapsule coated Ganoderma lucidum spore powder, from outside to inside is: polymer sustained-release coating and Ganoderma lucidum spore powder. The composite preparation provided by the present invention can not only protect the Cordyceps militaris extract from being eroded by gastric juice, but also enable Ganoderma lucidum spore powder to be pre-treated by gastric juice, so that both can reach the small intestine at the same time and be fully absorbed.

Description

Technical Field

[0001] This invention belongs to the field of compound preparation technology, specifically relating to a compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder and its application. Background Technology

[0002] Most health supplements on the market today contain only one ingredient, while compound preparations can provide richer nutrition and health benefits through the synergistic effect of multiple ingredients. Cordyceps militaris and Ganoderma lucidum spore powder are both precious Chinese medicinal materials with effects such as enhancing immunity and anti-oxidation.

[0003] However, because the absorption mechanisms and methods of each component in a compound preparation are different, it is difficult to achieve the goal of fully absorbing all components and enabling them to exert their effects. Summary of the Invention

[0004] The purpose of this invention is to provide a compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder and its application. Based on the absorption characteristics of various components by the human body, the sustained-release time and sustained-release site of the components are adjusted so that each component can be fully absorbed and the synergistic effect between the components is improved.

[0005] The above-mentioned technical objective of the present invention is achieved through the following technical solution:

[0006] The present invention provides a composite preparation of Cordyceps militaris and Ganoderma lucidum spore powder, wherein the composite preparation is microcapsule-encapsulated particles, the outer layer is a polylactic acid-glycolic acid copolymer film, and the inner layer is a composite particle of Cordyceps militaris extract and Ganoderma lucidum spore powder encapsulated in microcapsules.

[0007] According to the weight parts, the composite particles are composed of the following components: 20-30 parts of Cordyceps militaris extract encapsulated in microcapsules, 30-50 parts of Ganoderma lucidum spore powder encapsulated in microcapsules, and 10-15 parts of excipients.

[0008] Among them, the microcapsule-encapsulated Cordyceps militaris extract consists of, from the outside to the inside: an enteric coating layer and Cordyceps militaris extract;

[0009] The microcapsule-encapsulated Ganoderma lucidum spore powder consists of, from the outside to the inside: polymer slow-release coating and Ganoderma lucidum spore powder.

[0010] Furthermore, both the polymer sustained-release coating and the enteric coating are made of polyacrylic acid resin.

[0011] Furthermore, the enteric coating is made of polyacrylic acid resin with high carboxylic acid group density and polyacrylic acid resin with low carboxylic acid group density.

[0012] Furthermore, the mass ratio of low-carboxylic acid group density polyacrylic acid resin to high-carboxylic acid group density polyacrylic acid resin is calculated according to the following formula:

[0013] ;

[0014] in, β The mass ratio of low carboxylic acid group density polyacrylic resin to high carboxylic acid group density polyacrylic resin is expressed in 1;

[0015] α The ratio of the crosslinking density of the polymer sustained-release coating to the crosslinking density of the enteric layer, in units of 1, is calculated based on the ratio of the amount of crosslinking agent added to the amount of crosslinking agent added to the amount added to the enteric layer.

[0016] H L It represents the thickness of the polymer sustained-release coating, measured in nm.

[0017] H C It represents the thickness of the enteric coating, measured in nm.

[0018] Furthermore, the particle size of the composite particles is 20~80μm.

[0019] Furthermore, the particle size of the composite particles is 1~5μm.

[0020] Furthermore, the particle size of the microcapsule-encapsulated Cordyceps militaris extract is 0.1~0.8μm; the particle size of the microcapsule-encapsulated Ganoderma lucidum spore powder is 0.1~0.5μm.

[0021] Furthermore, the preparation method of microcapsule-encapsulated Cordyceps militaris extract is as follows:

[0022] Dissolve the polyacrylic acid resin in a solvent and stir until homogeneous to form a polyacrylic acid resin solution;

[0023] Add Cordyceps militaris extract to polyacrylic acid resin solution and stir until homogeneous;

[0024] Add an appropriate amount of emulsifier to form an emulsion;

[0025] The emulsion is emulsified under high-speed stirring to form stable emulsion particles;

[0026] A cross-linking agent is added dropwise to the emulsion to form cross-links between polyacrylic acid resin molecules, thereby forming the enteric coating layer of the microcapsules;

[0027] Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0028] Centrifugation and filtration were used to separate the microcapsules from the reaction mixture;

[0029] The microcapsules were washed to remove unreacted polyacrylic acid resin and other impurities, and then dried to obtain the microcapsules-encapsulated Cordyceps militaris extract.

[0030] Furthermore, the preparation method of the compound formulation provided by the present invention is as follows:

[0031] Microencapsulated Cordyceps militaris extract and microencapsulated Ganoderma lucidum spore powder were mixed in a certain proportion;

[0032] Add the excipients and mix well;

[0033] The uniformly mixed materials are granulated using a granulator to form composite particles;

[0034] Polylactic acid-glycolic acid copolymer is dissolved in a solvent to form a polylactic acid-glycolic acid copolymer solution;

[0035] The composite particles are immersed in a polylactic acid-glycolic acid copolymer solution to uniformly coat the surface of the composite particles with a polylactic acid-glycolic acid copolymer film.

[0036] The product is dried to form the composite formulation.

[0037] The present invention provides an application of a compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder, comprising: dissolving the compound preparation in water to prepare a powder for drinking.

[0038] Furthermore, the compound preparation can be made into tablets or capsules.

[0039] In summary, the present invention has the following beneficial effects:

[0040] This invention provides a compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder and its application. By adjusting the proportion of carboxylic acid groups in the microcapsule wall material, it can protect Cordyceps militaris extract from gastric juice erosion and allow Ganoderma lucidum spore powder to be pretreated by gastric juice, so that both can reach the small intestine at the same time and be fully absorbed, thus having an anti-aging effect. Attached Figure Description

[0041] Figure 1 This is a schematic diagram of the structure of the compound formulation in this invention;

[0042] Figure 2 This is a schematic diagram of the structure of the microcapsule-encapsulated Cordyceps militaris extract of the present invention;

[0043] Figure 3 This is a schematic diagram of the structure of microcapsule-encapsulated Ganoderma lucidum spore powder of the present invention.

[0044] Figure reference numerals: 1. Polylactic acid-glycolic acid copolymer film; 2. Composite particles; 3. Microcapsule-coated Cordyceps militaris extract; 4. Microcapsule-coated Ganoderma lucidum spore powder; 31. Enteric coating layer; 32. Cordyceps militaris extract; 41. Polymer sustained-release coating; 42. Ganoderma lucidum spore powder. Detailed Implementation

[0045] To further illustrate the technical means and effects adopted by the present invention to achieve the intended purpose, the specific implementation methods, features and effects of a Cordyceps militaris and Ganoderma lucidum spore powder compound preparation and its application according to the present invention are described in detail below.

[0046] Cordyceps militaris extract is an herb used in traditional Chinese medicine for hundreds of years. It is extracted from a fungus that parasitizes insect pupae and is commonly used to support the immune system, boost energy, and improve overall health. Cordyceps militaris extract contains various bioactive components, including polysaccharides, steroidal compounds, and adenosine, which have antioxidant, anti-inflammatory, and endurance-enhancing effects. Adenosine, a key component of Cordyceps militaris, helps improve energy metabolism, supports cardiovascular health, and has certain anti-fatigue and antioxidant properties.

[0047] However, some components in Cordyceps militaris extract, especially the more sensitive active ingredients such as adenosine and some polysaccharides, can be partially destroyed by gastric acid. The acidic environment of gastric acid and the action of digestive enzymes may lead to the degradation of these components, thereby affecting their biological activity.

[0048] In addition, Ganoderma lucidum spore powder is a powder extracted from the mature spores of Ganoderma lucidum. Ganoderma lucidum is a medicinal fungus widely used in traditional Chinese medicine and complementary medicine. Ganoderma lucidum spore powder is considered to be the essence of Ganoderma lucidum, rich in a variety of bioactive components, including triterpenoids, polysaccharides, adenosine, etc. Among them, triterpenoids help to enhance the immune system and improve the body's immune response.

[0049] However, due to the hardness of the spore shell in Ganoderma lucidum spore powder, the actual absorption effect is affected. Therefore, Ganoderma lucidum spore powder needs to stay in gastric juice for a period of time. After being processed by gastric acid, the active ingredients in Ganoderma lucidum spore powder can be fully absorbed when they reach the small intestine. If Ganoderma lucidum spore powder stays in gastric juice for too long, gastric acid will also destroy the biological activity of adenosine and triterpenoids in Ganoderma lucidum spore powder, affecting the absorption effect.

[0050] Therefore, how to simultaneously protect the adenosine in Cordyceps militaris extract and Ganoderma lucidum spore powder from being eroded by gastric acid, and also ensure that Ganoderma lucidum spore powder is properly treated by gastric juice, is a challenge in the preparation of compound preparations of Ganoderma lucidum spore powder and Cordyceps militaris extract.

[0051] To address the aforementioned issues, this specific embodiment provides a Cordyceps militaris and Ganoderma lucidum spore powder compound preparation that not only protects the Cordyceps militaris extract from gastric acid erosion but also allows the Ganoderma lucidum spore powder to be pre-treated by gastric acid, enabling both to reach the small intestine simultaneously and be fully absorbed.

[0052] The composite formulation provided in this specific embodiment is a microcapsule-encapsulated particle, with an outer layer of polylactic acid-glycolic acid copolymer film and an inner layer of composite particles containing microcapsules of Cordyceps militaris extract and microcapsules of Ganoderma lucidum spore powder.

[0053] According to the weight parts, the composite granules are composed of the following components: 20-30 parts of Cordyceps militaris extract encapsulated in microcapsules, 30-50 parts of Ganoderma lucidum spore powder encapsulated in microcapsules, and 10-15 parts of excipients.

[0054] Among them, the microcapsule-encapsulated Cordyceps militaris extract consists of, from the outside to the inside: an enteric coating layer and Cordyceps militaris extract;

[0055] The microcapsule-encapsulated Ganoderma lucidum spore powder consists of, from the outside to the inside: polymer slow-release coating and Ganoderma lucidum spore powder.

[0056] As can be seen from the above, different microcapsule encapsulation methods are used for different components. For the pH value of gastric acid, the wall material of the microcapsule encapsulating Cordyceps militaris extract is made of a more acid-resistant material so that it can reach the small intestine smoothly. On the other hand, the wall material of the microcapsule encapsulating Ganoderma lucidum spore powder is made of a material that can be slowly released in gastric acid so that it can be gradually released and reach the small intestine together with Cordyceps militaris after being treated by gastric acid, and be absorbed at the same time.

[0057] In one example, both the polymer sustained-release coating and the enteric coating are made of polyacrylic acid resin.

[0058] Understandably, the degree of crosslinking affects the dissolution rate and acid resistance of polymers. Low to moderate crosslinking allows the encapsulation material to dissolve moderately in acidic environments, thereby controlling the release rate. Too high a degree of crosslinking may lead to slow dissolution, while too low a degree may result in insufficient protection. In polymer science, the degree of crosslinking typically represents the density of crosslinks between polymer chains, that is, the degree to which polymer molecules are connected by chemical bonds. The value of the degree of crosslinking is usually expressed as crosslinking density or the proportion of crosslinking agent. The specific range depends on the materials used and the application. In pharmaceutical formulations, especially in microencapsulation technology, the degree of crosslinking usually needs to be controlled within a moderate range to achieve optimal drug release characteristics.

[0059] In this specific embodiment, crosslinking density is used to represent the degree of crosslinking of the polymer, and the slow release rate of Ganoderma lucidum spore powder and Cordyceps militaris extract in gastric acid is determined according to the ratio of the degree of crosslinking, so as to ensure that Cordyceps militaris extract is not eroded by gastric acid, while Ganoderma lucidum spore powder is treated by gastric acid through slow release.

[0060] In one example, the enteric coating material is a polyacrylic acid resin with high carboxylic acid group density and a polyacrylic acid resin with low carboxylic acid group density.

[0061] It should be noted that the solubility and application characteristics of polyacrylic acid resins largely depend on the density of their carboxylic acid groups (-COOH). The density of carboxylic acid groups directly affects the resin's solubility behavior in different pH environments. Therefore, different types of polyacrylic acid resins can be distinguished by the difference in the density of carboxylic acid groups.

[0062] It is understandable that carboxylic acid group density refers to the number of carboxylic acid groups per unit mass or volume in a polymer. Resins with high density are more likely to dissociate and dissolve in a low pH environment, while resins with low density require a higher pH value to dissociate.

[0063] Among them, high carboxylic acid group density polyacrylic acid resin: This resin contains more methacrylic acid (MAA) or acrylic acid (AA) monomers in its structure. These monomers contain carboxylic acid groups, which makes the resin soluble at lower pH values ​​(such as below pH=5).

[0064] Medium carboxylic acid group density polyacrylic acid resins: These resins contain an appropriate amount of carboxylic acid groups and are usually soluble between pH 5 and 7.

[0065] Low carboxylic acid group density polyacrylic acid resins: These resins contain a lower density of carboxylic acid groups, and therefore can only dissolve at higher pH values ​​(e.g., above pH 7). A low carboxylic acid group density is typically achieved by introducing more neutral or hydrophobic monomers (such as methyl methacrylate, MMA).

[0066] Specifically, in this embodiment, the high carboxylic acid group density polyacrylic acid resin has a molar mass percentage of 30% for carboxylic acid groups and a molar mass percentage of 10% for low carboxylic acid group density polyacrylic acid resin.

[0067] In one example, the mass ratio of low carboxylic acid group density polyacrylic resin to high carboxylic acid group density polyacrylic resin is calculated according to the following formula:

[0068] ;

[0069] in, β The mass ratio of low carboxylic acid group density polyacrylic resin to high carboxylic acid group density polyacrylic resin is expressed in 1;

[0070] α The ratio of the crosslinking density of the polymer sustained-release coating to the crosslinking density of the enteric layer, in units of 1, is calculated based on the ratio of the amount of crosslinking agent added to the amount of crosslinking agent added to the amount added to the enteric layer.

[0071] H L It represents the thickness of the polymer sustained-release coating, measured in nm.

[0072] H C It represents the thickness of the enteric coating, measured in nm.

[0073] It is understandable that in the above formula, β The meaning of represents the mass ratio of polyacrylic acid resin with low carboxylic acid group density to resin with high carboxylic acid group density. This is used to measure the proportion of different resins in a mixture, which affects the solubility and release characteristics of the final material. α The term "crosslinking density" indicates the relative magnitude of the crosslinking density between the two layers (sustained-release coating and enteric coating). Crosslinking density affects the mechanical properties and solubility behavior of the material. H L / H C The term "total thickness" represents the ratio of the sustained-release coating to the enteric coating, a ratio that can affect the drug release rate and solubility characteristics. Considering these factors, the formula provided in this specific embodiment describes the proportional relationship between different components and structural layers in a composite material; specifically, it relates to the proportion of different types of polyacrylic acid resins (…). β The crosslinking density ratio and thickness ratio of these resins in their respective functional layers (sustained-release layer and enteric layer) in multilayer drug coatings help to design and optimize the release characteristics of drug formulations, such as release rate, to meet specific therapeutic needs.

[0074] Specifically, in this embodiment, the higher the ratio of the crosslinking density of the polymer sustained-release coating to the crosslinking density of the enteric coating, the slower the sustained-release rate of the microcapsule-encapsulated Cordyceps militaris extract compared to the microcapsule-encapsulated Ganoderma lucidum spore powder. Therefore, reducing the content of low carboxylic acid group density polyacrylic acid resin in the enteric coating material can increase the sustained-release rate of the enteric coating in the small intestine, thereby ensuring that Ganoderma lucidum spore powder and Cordyceps militaris extract can be absorbed simultaneously.

[0075] In one example, the particle size of the composite particles is 20~80μm.

[0076] In one example, the particle size of the composite particles is 1~5μm.

[0077] In one example, the particle size of the microcapsules encapsulating Cordyceps militaris extract is 0.1~0.8μm; the particle size of the microcapsules encapsulating Ganoderma lucidum spore powder is 0.1~0.5μm.

[0078] Understandably, microencapsulation can prevent active ingredients from being directly exposed to adverse environments, increase stability, and control the size of microcapsules can precisely regulate the drug release rate. In this specific embodiment, the use of composite particles and microcapsules of different particle sizes is to optimize drug release characteristics, improve bioavailability and stability, and meet different dosing needs and therapeutic effects. These settings help to achieve personalized drug treatment, maximize its therapeutic effect and minimize side effects.

[0079] In one example, the method for preparing microcapsule-encapsulated Cordyceps militaris extract is as follows:

[0080] Dissolve high carboxylic acid group density polyacrylic acid resin and low carboxylic acid group density polyacrylic acid resin in a solvent and stir until homogeneous to form a homogeneous polyacrylic acid resin solution.

[0081] Add Cordyceps militaris extract to polyacrylic acid resin solution and stir until homogeneous;

[0082] Add an appropriate amount of emulsifier to form an emulsion;

[0083] The emulsion is emulsified under high-speed stirring to form stable emulsion particles;

[0084] A cross-linking agent is added dropwise to the emulsion to form cross-links between polyacrylic acid resin molecules, thereby forming the enteric coating layer of the microcapsules;

[0085] Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0086] Centrifugation and filtration were used to separate the microcapsules from the reaction mixture;

[0087] The microcapsules were washed to remove unreacted polyacrylic acid resin and other impurities, and then dried to obtain the microcapsules-encapsulated Cordyceps militaris extract.

[0088] In some preferred examples, Tween 80 is selected as the emulsifier, glutaraldehyde is selected as the crosslinking agent, and the concentration of the crosslinking agent is determined according to the degree of crosslinking. Preferably, the concentration of the crosslinking agent is 1% to 5% wt of the polyacrylic acid resin.

[0089] In one example, the preparation method of microcapsule-encapsulated Ganoderma lucidum spore powder is as follows:

[0090] Dissolve high carboxylic acid group density polyacrylic acid resin in a solvent and stir until homogeneous to form a homogeneous polyacrylic acid resin solution.

[0091] Add Ganoderma lucidum spore powder to polyacrylic acid resin solution and stir well;

[0092] Add an appropriate amount of emulsifier to form an emulsion;

[0093] The emulsion is emulsified under high-speed stirring to form stable emulsion particles;

[0094] A cross-linking agent is added dropwise to the emulsion to form cross-links between polyacrylic acid resin molecules, thereby forming a polymer sustained-release coating for microcapsules.

[0095] Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0096] Centrifugation and filtration were used to separate the microcapsules from the reaction mixture;

[0097] The microcapsules are washed to remove unreacted polyacrylic acid resin and other impurities, and then dried to obtain the microcapsule-encapsulated Ganoderma lucidum spore powder.

[0098] In this specific embodiment, using polyacrylic acid resin with a high carboxylic acid group density as the wall material of Ganoderma lucidum spore powder allows the Ganoderma lucidum spore powder to be acid-treated in gastric juice, making the spore shell more easily soluble in intestinal juice, while at the same time preventing the Ganoderma lucidum spore powder from being overly exposed to gastric acid, which would cause the active ingredients to be destroyed by gastric acid.

[0099] In some preferred examples, Tween 80 is selected as the emulsifier, glutaraldehyde is selected as the crosslinking agent, and the concentration of the crosslinking agent is determined according to the degree of crosslinking. Preferably, the concentration of the crosslinking agent is 0.2% to 1% wt of the polyacrylic acid resin.

[0100] In one example, the preparation method of Cordyceps militaris extract uses alcohol extraction to obtain more adenosine; the cell wall breakage rate of Ganoderma lucidum spore powder is selected to be above 90% to improve the absorption rate of Ganoderma lucidum spore powder.

[0101] In one example, the preparation method of the compound formulation is as follows:

[0102] Microencapsulated Cordyceps militaris extract and microencapsulated Ganoderma lucidum spore powder were mixed in a certain proportion;

[0103] Add the excipients and mix well;

[0104] The uniformly mixed materials are granulated using a granulator to form composite particles;

[0105] Polylactic acid-glycolic acid copolymer is dissolved in a solvent to form a polylactic acid-glycolic acid copolymer solution;

[0106] The composite particles are immersed in a polylactic acid-glycolic acid copolymer solution to uniformly coat the surface of the composite particles with a polylactic acid-glycolic acid copolymer film.

[0107] The product is dried to form the composite formulation.

[0108] In some preferred embodiments, the excipient is typically selected β-Cyclodextrin.

[0109] This specific embodiment also provides an application of a compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder, including: dissolving the compound preparation in water to make a powder for drinking.

[0110] It should be noted that the high carboxylic acid group density polyacrylic acid resin used in the following examples is Eudragit L; the low carboxylic acid group density polyacrylic acid resin is Eudragit S; and the excipients are... β -Cyclodextrin.

[0111] In some preferred embodiments, the compound formulation is prepared into tablets or capsules.

[0112] Example 1: A compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder and its application

[0113] This embodiment provides a Cordyceps militaris and Ganoderma lucidum spore powder composite preparation with a particle size of 60μm. The outer layer is a polylactic acid-glycolic acid copolymer film, and the inner layer is a composite particle of Cordyceps militaris extract and Ganoderma lucidum spore powder encapsulated in microcapsules.

[0114] The composite particles have a particle size of 4μm and are composed of the following components by weight: 20 parts of Cordyceps militaris extract encapsulated in microcapsules, 30 parts of Ganoderma lucidum spore powder encapsulated in microcapsules, and 10 parts of excipients.

[0115] Among them, the microcapsule-encapsulated Cordyceps militaris extract consists of, from the outside to the inside: an enteric coating layer and Cordyceps militaris extract;

[0116] The microcapsule-encapsulated Ganoderma lucidum spore powder consists of, from the outside to the inside: polymer slow-release coating and Ganoderma lucidum spore powder.

[0117] The microcapsule-encapsulated Cordyceps militaris extract has a particle size of 0.6 μm and an enteric coating thickness of 20 nm. The preparation method, calculated by weight, is as follows:

[0118] S1. Dissolve 10 parts by weight of high carboxylic acid group density polyacrylic acid resin and low carboxylic acid group density polyacrylic acid resin in ethyl acetate, stir until homogeneous, and form a homogeneous polyacrylic acid resin solution.

[0119] S2. Add 30 parts of Cordyceps militaris extract to the polyacrylic acid resin solution and stir until homogeneous;

[0120] S3. Add 5 parts of emulsifier Tween 80 to form an emulsion;

[0121] S4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0122] S5. Add 1.5 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming the enteric coating layer of the microcapsules;

[0123] S6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0124] S7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0125] S8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain the microcapsule-encapsulated Cordyceps militaris extract.

[0126] The microcapsule-encapsulated Ganoderma lucidum spore powder has a particle size of 0.4 μm and a polymer sustained-release coating thickness of 15 nm. The preparation method, calculated by weight parts, is as follows:

[0127] A1. Dissolve 10 parts of high carboxylic acid group density polyacrylic acid resin in ethyl acetate and stir until homogeneous to form a homogeneous polyacrylic acid resin solution.

[0128] A2. Add 20 portions of Ganoderma lucidum spore powder to the polyacrylic acid resin solution and stir until well mixed;

[0129] A3. Add an appropriate amount of 5 parts of emulsifier Tween 80 to form an emulsion;

[0130] A4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0131] A5. Add 0.75 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming a polymer sustained-release coating for microcapsules;

[0132] A6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0133] A7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0134] A8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain microcapsule-encapsulated Ganoderma lucidum spore powder.

[0135] The mass ratio of low carboxylic acid group density polyacrylic acid resin to high carboxylic acid group density polyacrylic acid resin is calculated according to the following formula:

[0136] ;

[0137] in, β The mass ratio of low carboxylic acid group density polyacrylic resin to high carboxylic acid group density polyacrylic resin is expressed in 1;

[0138] αThe ratio of the crosslinking density of the polymer sustained-release coating to the crosslinking density of the enteric layer, in units of 1, is calculated based on the ratio of the amount of crosslinking agent added to the amount of crosslinking agent added to the enteric layer, and the value is 0.5.

[0139] H L It represents the thickness of the polymer sustained-release coating, measured in nm.

[0140] H C It is the thickness of the enteric coating, measured in nm;

[0141] In this embodiment, β =0.4.

[0142] Among them, the preparation method of Cordyceps militaris extract adopts alcohol extraction; the cell wall breakage rate of Ganoderma lucidum spore powder is over 90%.

[0143] The preparation method of the compound formulation provided in this embodiment is as follows:

[0144] Step 1: Mix 20 parts of microcapsule-encapsulated Cordyceps militaris extract with 30 parts of microcapsule-encapsulated Ganoderma lucidum spore powder in a certain proportion;

[0145] Step 2: Add 10 parts cyclodextrin and water, and mix well;

[0146] Step 3: Granulate the uniformly mixed materials using a pelletizer to form composite granules;

[0147] Step 4: Dissolve the polylactic acid-glycolic acid copolymer in a solvent to form a polylactic acid-glycolic acid copolymer solution;

[0148] Step 5: Immerse the composite particles in a polylactic acid-glycolic acid copolymer solution to uniformly coat the surface of the composite particles with a polylactic acid-glycolic acid copolymer film;

[0149] Step 6: Drying to form the composite formulation.

[0150] This embodiment also provides an application of a compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder, including: dissolving 30g of the compound preparation in 100g of water to make a powder for drinking.

[0151] Example 2: A compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder and its application

[0152] This embodiment provides a Cordyceps militaris and Ganoderma lucidum spore powder composite preparation with a particle size of 50μm. The outer layer is a polylactic acid-glycolic acid copolymer film, and the inner layer is a composite particle of Cordyceps militaris extract and Ganoderma lucidum spore powder microcapsules.

[0153] The composite particles have a particle size of 3μm and are composed of the following components by weight: 20 parts of Cordyceps militaris extract encapsulated in microcapsules, 35 parts of Ganoderma lucidum spore powder encapsulated in microcapsules, and 10 parts of excipients.

[0154] Among them, the microcapsule-encapsulated Cordyceps militaris extract consists of, from the outside to the inside: an enteric coating layer and Cordyceps militaris extract;

[0155] The microcapsule-encapsulated Ganoderma lucidum spore powder consists of, from the outside to the inside: polymer slow-release coating and Ganoderma lucidum spore powder.

[0156] The microcapsule-encapsulated Cordyceps militaris extract has a particle size of 0.6 μm and an enteric coating thickness of 20 nm. The preparation method, calculated by weight, is as follows:

[0157] S1. Dissolve 10 parts by weight of high carboxylic acid group density polyacrylic acid resin and low carboxylic acid group density polyacrylic acid resin in ethyl acetate, stir until homogeneous, and form a homogeneous polyacrylic acid resin solution.

[0158] S2. Add 30 parts of Cordyceps militaris extract to the polyacrylic acid resin solution and stir until homogeneous;

[0159] S3. Add 5 parts of emulsifier Tween 80 to form an emulsion;

[0160] S4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0161] S5. Add 1.8 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming the enteric coating layer of the microcapsules;

[0162] S6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0163] S7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0164] S8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain the microcapsule-encapsulated Cordyceps militaris extract.

[0165] The microcapsule-encapsulated Ganoderma lucidum spore powder has a particle size of 0.4 μm and a polymer sustained-release coating thickness of 15 nm. The preparation method, calculated by weight parts, is as follows:

[0166] A1. Dissolve 10 parts of high carboxylic acid group density polyacrylic acid resin in ethyl acetate and stir until homogeneous to form a homogeneous polyacrylic acid resin solution.

[0167] A2. Add 20 portions of Ganoderma lucidum spore powder to the polyacrylic acid resin solution and stir until well mixed;

[0168] A3. Add an appropriate amount of 5 parts of emulsifier Tween 80 to form an emulsion;

[0169] A4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0170] A5. Add 0.8 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming a polymer sustained-release coating for microcapsules;

[0171] A6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0172] A7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0173] A8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain microcapsule-encapsulated Ganoderma lucidum spore powder.

[0174] The mass ratio of low carboxylic acid group density polyacrylic acid resin to high carboxylic acid group density polyacrylic acid resin is calculated according to the following formula:

[0175] ;

[0176] in, β The mass ratio of low carboxylic acid group density polyacrylic resin to high carboxylic acid group density polyacrylic resin is expressed in 1;

[0177] α The ratio of the crosslinking density of the polymer sustained-release coating to the crosslinking density of the enteric coating, in units of 1, is calculated based on the ratio of the amount of crosslinking agent added to the amount of crosslinking agent added to the enteric coating, and the value is 0.44.

[0178] H L It represents the thickness of the polymer sustained-release coating, measured in nm.

[0179] H C It is the thickness of the enteric coating, measured in nm;

[0180] In this embodiment, β =0.33.

[0181] Among them, the preparation method of Cordyceps militaris extract adopts alcohol extraction; the cell wall breakage rate of Ganoderma lucidum spore powder is over 90%.

[0182] The preparation method of the compound formulation provided in this embodiment is as follows:

[0183] Step 1: Mix 20 parts of microcapsule-encapsulated Cordyceps militaris extract with 30 parts of microcapsule-encapsulated Ganoderma lucidum spore powder in a certain proportion;

[0184] Step 2: Add 10 parts cyclodextrin and water, and mix well;

[0185] Step 3: Granulate the uniformly mixed materials using a pelletizer to form composite granules;

[0186] Step 4: Dissolve the polylactic acid-glycolic acid copolymer in a solvent to form a polylactic acid-glycolic acid copolymer solution;

[0187] Step 5: Immerse the composite particles in a polylactic acid-glycolic acid copolymer solution to uniformly coat the surface of the composite particles with a polylactic acid-glycolic acid copolymer film;

[0188] Step 6: Drying to form a compound preparation.

[0189] This embodiment also provides an application of a compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder, including: dissolving 30g of the compound preparation in 100g of water to make a powder for drinking.

[0190] Example 3: A compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder and its application

[0191] This embodiment provides a Cordyceps militaris and Ganoderma lucidum spore powder composite preparation with a particle size of 45μm. The outer layer is a polylactic acid-glycolic acid copolymer film, and the inner layer is a composite particle of Cordyceps militaris extract and Ganoderma lucidum spore powder microcapsules.

[0192] The composite particles have a particle size of 6μm and are composed of the following components by weight: 20 parts of Cordyceps militaris extract encapsulated in microcapsules, 35 parts of Ganoderma lucidum spore powder encapsulated in microcapsules, and 10 parts of excipients.

[0193] Among them, the microcapsule-encapsulated Cordyceps militaris extract consists of, from the outside to the inside: an enteric coating layer and Cordyceps militaris extract;

[0194] The microcapsule-encapsulated Ganoderma lucidum spore powder consists of, from the outside to the inside: polymer slow-release coating and Ganoderma lucidum spore powder.

[0195] The microcapsule-encapsulated Cordyceps militaris extract has a particle size of 0.7 μm and an enteric coating thickness of 20 nm. The preparation method, calculated by weight, is as follows:

[0196] S1. Dissolve 10 parts by weight of high carboxylic acid group density polyacrylic acid resin and low carboxylic acid group density polyacrylic acid resin in ethyl acetate, stir until homogeneous, and form a homogeneous polyacrylic acid resin solution.

[0197] S2. Add 30 parts of Cordyceps militaris extract to the polyacrylic acid resin solution and stir until homogeneous;

[0198] S3. Add 5 parts of emulsifier Tween 80 to form an emulsion;

[0199] S4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0200] S5. Add 1.2 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming the enteric coating layer of the microcapsules;

[0201] S6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0202] S7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0203] S8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain the microcapsule-encapsulated Cordyceps militaris extract.

[0204] The microcapsule-encapsulated Ganoderma lucidum spore powder has a particle size of 0.5 μm and a polymer sustained-release coating thickness of 15 nm. The preparation method, calculated by weight parts, is as follows:

[0205] A1. Dissolve 10 parts of high carboxylic acid group density polyacrylic acid resin in ethyl acetate and stir until homogeneous to form a homogeneous polyacrylic acid resin solution.

[0206] A2. Add 20 portions of Ganoderma lucidum spore powder to the polyacrylic acid resin solution and stir until well mixed;

[0207] A3. Add an appropriate amount of 5 parts of emulsifier Tween 80 to form an emulsion;

[0208] A4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0209] A5. Add 0.8 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming a polymer sustained-release coating for microcapsules;

[0210] A6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0211] A7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0212] A8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain microcapsule-encapsulated Ganoderma lucidum spore powder.

[0213] The mass ratio of low carboxylic acid group density polyacrylic acid resin to high carboxylic acid group density polyacrylic acid resin is calculated according to the following formula:

[0214] ;

[0215] in, β The mass ratio of low carboxylic acid group density polyacrylic resin to high carboxylic acid group density polyacrylic resin is expressed in 1;

[0216] α The ratio of the crosslinking density of the polymer sustained-release coating to the crosslinking density of the enteric layer, in units of 1, is calculated based on the ratio of the amount of crosslinking agent added to the amount of crosslinking agent added to the enteric layer, and the value is 0.66.

[0217] H L It represents the thickness of the polymer sustained-release coating, measured in nm.

[0218] H C It is the thickness of the enteric coating, measured in nm;

[0219] In this embodiment, β =0.5.

[0220] Among them, the preparation method of Cordyceps militaris extract adopts alcohol extraction; the cell wall breakage rate of Ganoderma lucidum spore powder is over 90%.

[0221] The preparation method of the compound formulation provided in this embodiment is as follows:

[0222] Step 1: Mix 20 parts of microcapsule-encapsulated Cordyceps militaris extract with 30 parts of microcapsule-encapsulated Ganoderma lucidum spore powder in a certain proportion;

[0223] Step 2: Add 10 parts cyclodextrin and water, and mix well;

[0224] Step 3: Granulate the uniformly mixed materials using a pelletizer to form composite granules;

[0225] Step 4: Dissolve the polylactic acid-glycolic acid copolymer in a solvent to form a polylactic acid-glycolic acid copolymer solution;

[0226] Step 5: Immerse the composite particles in a polylactic acid-glycolic acid copolymer solution to uniformly coat the surface of the composite particles with a polylactic acid-glycolic acid copolymer film;

[0227] Step 6: Drying to form a compound preparation.

[0228] This embodiment also provides an application of a compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder, including: dissolving 30g of the compound preparation in 100g of water to make a powder for drinking.

[0229] Comparative Example 1: A compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder and its application

[0230] This embodiment provides a Cordyceps militaris and Ganoderma lucidum spore powder composite preparation with a particle size of 60μm. The outer layer is a polylactic acid-glycolic acid copolymer film, and the inner layer is a composite particle of Cordyceps militaris extract and Ganoderma lucidum spore powder encapsulated in microcapsules.

[0231] The composite particles have a particle size of 4μm and are composed of the following components by weight: 20 parts of Cordyceps militaris extract encapsulated in microcapsules, 30 parts of Ganoderma lucidum spore powder encapsulated in microcapsules, and 10 parts of excipients.

[0232] Among them, the microcapsule-encapsulated Cordyceps militaris extract consists of, from the outside to the inside: an enteric coating layer and Cordyceps militaris extract;

[0233] The microcapsule-encapsulated Ganoderma lucidum spore powder consists of, from the outside to the inside: polymer slow-release coating and Ganoderma lucidum spore powder.

[0234] The microcapsule-encapsulated Cordyceps militaris extract has a particle size of 0.6 μm and an enteric coating thickness of 20 nm. The preparation method, calculated by weight, is as follows:

[0235] S1. Dissolve 10 parts of high carboxylic acid group density polyacrylic acid resin in ethyl acetate and stir until homogeneous to form a homogeneous polyacrylic acid resin solution.

[0236] S2. Add 30 parts of Cordyceps militaris extract to the polyacrylic acid resin solution and stir until homogeneous;

[0237] S3. Add 5 parts of emulsifier Tween 80 to form an emulsion;

[0238] S4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0239] S5. Add 1.5 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming the enteric coating layer of the microcapsules;

[0240] S6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0241] S7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0242] S8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain the microcapsule-encapsulated Cordyceps militaris extract.

[0243] The microcapsule-encapsulated Ganoderma lucidum spore powder has a particle size of 0.4 μm and a polymer sustained-release coating thickness of 15 nm. The preparation method, calculated by weight parts, is as follows:

[0244] A1. Dissolve 10 parts of high carboxylic acid group density polyacrylic acid resin in ethyl acetate and stir until homogeneous to form a homogeneous polyacrylic acid resin solution.

[0245] A2. Add 20 portions of Ganoderma lucidum spore powder to the polyacrylic acid resin solution and stir until well mixed;

[0246] A3. Add an appropriate amount of 5 parts of emulsifier Tween 80 to form an emulsion;

[0247] A4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0248] A5. Add 0.75 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming a polymer sustained-release coating for microcapsules;

[0249] A6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0250] A7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0251] A8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain microcapsule-encapsulated Ganoderma lucidum spore powder.

[0252] Among them, the preparation method of Cordyceps militaris extract adopts alcohol extraction; the cell wall breakage rate of Ganoderma lucidum spore powder is over 90%.

[0253] The preparation method of the compound formulation provided in this embodiment is as follows:

[0254] Step 1: Mix 20 parts of microcapsule-encapsulated Cordyceps militaris extract with 30 parts of microcapsule-encapsulated Ganoderma lucidum spore powder in a certain proportion;

[0255] Step 2: Add 10 parts cyclodextrin and water, and mix well;

[0256] Step 3: Granulate the uniformly mixed materials using a pelletizer to form composite granules;

[0257] Step 4: Dissolve the polylactic acid-glycolic acid copolymer in a solvent to form a polylactic acid-glycolic acid copolymer solution;

[0258] Step 5: Immerse the composite particles in a polylactic acid-glycolic acid copolymer solution to uniformly coat the surface of the composite particles with a polylactic acid-glycolic acid copolymer film;

[0259] Step 6: Drying to form the composite formulation.

[0260] This embodiment also provides an application of a compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder, including: dissolving 30g of the compound preparation in 100g of water to make a powder for drinking.

[0261] Comparative Example 2: A compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder and its application

[0262] This embodiment provides a Cordyceps militaris and Ganoderma lucidum spore powder composite preparation with a particle size of 60μm. The outer layer is a polylactic acid-glycolic acid copolymer film, and the inner layer is a composite particle of Cordyceps militaris extract and Ganoderma lucidum spore powder encapsulated in microcapsules.

[0263] The composite particles have a particle size of 4μm and are composed of the following components by weight: 20 parts of Cordyceps militaris extract encapsulated in microcapsules, 30 parts of Ganoderma lucidum spore powder encapsulated in microcapsules, and 10 parts of excipients.

[0264] Among them, the microcapsule-encapsulated Cordyceps militaris extract consists of, from the outside to the inside: an enteric coating layer and Cordyceps militaris extract;

[0265] The microcapsule-encapsulated Ganoderma lucidum spore powder consists of, from the outside to the inside: polymer slow-release coating and Ganoderma lucidum spore powder.

[0266] The microcapsule-encapsulated Cordyceps militaris extract has a particle size of 0.6 μm and an enteric coating thickness of 20 nm. The preparation method, calculated by weight, is as follows:

[0267] S1. Dissolve 10 parts of low carboxylic acid group density polyacrylic acid resin in ethyl acetate and stir until homogeneous to form a homogeneous polyacrylic acid resin solution.

[0268] S2. Add 30 parts of Cordyceps militaris extract to the polyacrylic acid resin solution and stir until homogeneous;

[0269] S3. Add 5 parts of emulsifier Tween 80 to form an emulsion;

[0270] S4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0271] S5. Add 1.5 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming the wall material of the microcapsules;

[0272] S6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0273] S7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0274] S8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain the microcapsule-encapsulated Cordyceps militaris extract.

[0275] The microcapsule-encapsulated Ganoderma lucidum spore powder has a particle size of 0.4 μm and a polymer sustained-release coating thickness of 15 nm. The preparation method, calculated by weight parts, is as follows:

[0276] A1. Dissolve 10 parts of high carboxylic acid group density polyacrylic acid resin in ethyl acetate and stir until homogeneous to form a homogeneous polyacrylic acid resin solution.

[0277] A2. Add 20 portions of Ganoderma lucidum spore powder to the polyacrylic acid resin solution and stir until well mixed;

[0278] A3. Add an appropriate amount of 5 parts of emulsifier Tween 80 to form an emulsion;

[0279] A4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0280] A5. Add 0.75 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming the wall material of the microcapsules;

[0281] A6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0282] A7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0283] A8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain microcapsule-encapsulated Ganoderma lucidum spore powder.

[0284] Among them, the preparation method of Cordyceps militaris extract adopts alcohol extraction; the cell wall breakage rate of Ganoderma lucidum spore powder is over 90%.

[0285] The preparation method of the compound formulation provided in this embodiment is as follows:

[0286] Step 1: Mix 20 parts of microcapsule-encapsulated Cordyceps militaris extract with 30 parts of microcapsule-encapsulated Ganoderma lucidum spore powder in a certain proportion;

[0287] Step 2: Add 10 parts cyclodextrin and water, and mix well;

[0288] Step 3: Granulate the uniformly mixed materials using a pelletizer to form composite granules;

[0289] Step 4: Dissolve the polylactic acid-glycolic acid copolymer in a solvent to form a polylactic acid-glycolic acid copolymer solution;

[0290] Step 5: Immerse the composite particles in a polylactic acid-glycolic acid copolymer solution to uniformly coat the surface of the composite particles with a polylactic acid-glycolic acid copolymer film;

[0291] Step 6: Drying to form the composite formulation.

[0292] This embodiment also provides an application of a compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder, including: dissolving 30g of the compound preparation in 100g of water to make a powder for drinking.

[0293] Comparative Example 3: A compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder and its application

[0294] This embodiment provides a Cordyceps militaris and Ganoderma lucidum spore powder composite preparation with a particle size of 60μm. The outer layer is a polylactic acid-glycolic acid copolymer film, and the inner layer is a composite particle of Cordyceps militaris extract and Ganoderma lucidum spore powder encapsulated in microcapsules.

[0295] The composite particles have a particle size of 4μm and are composed of the following components by weight: 20 parts of Cordyceps militaris extract encapsulated in microcapsules, 30 parts of Ganoderma lucidum spore powder encapsulated in microcapsules, and 10 parts of excipients.

[0296] Among them, the microcapsule-encapsulated Cordyceps militaris extract consists of, from the outside to the inside: an enteric coating layer and Cordyceps militaris extract;

[0297] The microcapsule-encapsulated Ganoderma lucidum spore powder consists of, from the outside to the inside: polymer slow-release coating and Ganoderma lucidum spore powder.

[0298] The microcapsule-encapsulated Cordyceps militaris extract has a particle size of 0.6 μm and an enteric coating thickness of 20 nm. The preparation method, calculated by weight, is as follows:

[0299] S1. Dissolve 5 parts of high carboxylic acid group density polyacrylic acid resin and 5 parts of low carboxylic acid group density polyacrylic acid resin in ethyl acetate, with a total weight of 10 parts, stir evenly to form a homogeneous polyacrylic acid resin solution.

[0300] S2. Add 30 parts of Cordyceps militaris extract to the polyacrylic acid resin solution and stir until homogeneous;

[0301] S3. Add 5 parts of emulsifier Tween 80 to form an emulsion;

[0302] S4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0303] S5. Add 1.5 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming the enteric coating layer of the microcapsules;

[0304] S6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0305] S7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0306] S8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain the microcapsule-encapsulated Cordyceps militaris extract.

[0307] The microcapsule-encapsulated Ganoderma lucidum spore powder has a particle size of 0.4 μm and a polymer sustained-release coating thickness of 15 nm. The preparation method, calculated by weight parts, is as follows:

[0308] A1. Dissolve 10 parts of high carboxylic acid group density polyacrylic acid resin in ethyl acetate and stir until homogeneous to form a homogeneous polyacrylic acid resin solution.

[0309] A2. Add 20 portions of Ganoderma lucidum spore powder to the polyacrylic acid resin solution and stir until well mixed;

[0310] A3. Add an appropriate amount of 5 parts of emulsifier Tween 80 to form an emulsion;

[0311] A4. Emulsify the emulsion under high-speed stirring to form stable emulsion particles;

[0312] A5. Add 0.75 parts of glutaraldehyde crosslinking agent dropwise to the emulsion to form crosslinks between polyacrylic acid resin molecules, thereby forming a polymer sustained-release coating for microcapsules;

[0313] A6. Continue stirring the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed;

[0314] A7. Centrifuge and filter to separate the microcapsules from the reaction mixture;

[0315] A8. Wash the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and dry them to obtain microcapsule-encapsulated Ganoderma lucidum spore powder.

[0316] Among them, the preparation method of Cordyceps militaris extract adopts alcohol extraction; the cell wall breakage rate of Ganoderma lucidum spore powder is over 90%.

[0317] The preparation method of the compound formulation provided in this embodiment is as follows:

[0318] Step 1: Mix 20 parts of microcapsule-encapsulated Cordyceps militaris extract with 30 parts of microcapsule-encapsulated Ganoderma lucidum spore powder in a certain proportion;

[0319] Step 2: Add 10 parts cyclodextrin and water, and mix well;

[0320] Step 3: Granulate the uniformly mixed materials using a pelletizer to form composite granules;

[0321] Step 4: Dissolve the polylactic acid-glycolic acid copolymer in a solvent to form a polylactic acid-glycolic acid copolymer solution;

[0322] Step 5: Immerse the composite particles in a polylactic acid-glycolic acid copolymer solution to uniformly coat the surface of the composite particles with a polylactic acid-glycolic acid copolymer film;

[0323] Step 6: Drying to form the composite formulation.

[0324] This embodiment also provides an application of a compound preparation of Cordyceps militaris and Ganoderma lucidum spore powder, including: dissolving 30g of the compound preparation in 100g of water to make a powder for drinking.

[0325] In vitro enteric coating experiments were conducted on the composite powders obtained in Examples 1-3 and Comparative Examples 1-3. The specific methods are as follows:

[0326] 1. Experimental equipment and materials

[0327] Dissolution tester: Use a USP dissolution tester.

[0328] Dissolution media: simulated gastric juice (pH=1.2), simulated intestinal juice (pH=6.8) and simulated colonic juice (pH=7.4).

[0329] Formulation samples: compound formulations of Examples 1-3 and Comparative Examples 1-3.

[0330] 2. Experimental Procedure

[0331] (1) Simulation of the gastric environment to evaluate the ability of the drug to remain stable in the acidic gastric environment. The compound preparations obtained in Examples 1-3 and Comparative Examples 1-3 were placed in simulated gastric fluid with pH=1.2 and kept for 1 hour. During this period, samples were taken periodically to determine the amount of drug released.

[0332] (2) Transfer to the intestinal environment to simulate the dissolution and release of the drug in the intestine. The preparation is taken out of the gastric juice and transferred to the simulated intestinal juice with pH=6.8. This process is carried out at 37°C to simulate the human body temperature and is continuously dissolved for 2 hours. The amount of drug released is measured periodically.

[0333] Table 1. Preparation parameters and test results

[0334]

[0335] Comparing Comparative Example 1 with Example 1, it can be seen that when high carboxylic acid group density polyacrylate is used as the wall material, Cordyceps militaris extract is partially released in gastric juice. This indicates that Cordyceps militaris extract has been eroded by gastric juice. Furthermore, the release rate of Cordyceps militaris extract in intestinal juice is relatively fast, almost the same as that of Ganoderma lucidum spore powder. However, the absorption time of Ganoderma lucidum spore powder is longer than that of Cordyceps militaris extract. This results in some Ganoderma lucidum spore powder not being absorbed when Cordyceps militaris extract has been completely absorbed, thus affecting the synergistic effect of the two components.

[0336] Comparing Comparative Example 2 with Example 1, it can be seen that when low carboxylic acid group density polyacrylate is used as the wall material, Cordyceps militaris extract does not dissolve in gastric juice, and its release rate in intestinal juice is also slow. In contrast, Ganoderma lucidum spore powder is released faster. Although the absorption of Ganoderma lucidum spore powder takes longer, since it has already been processed by gastric juice, its absorption rate in the small intestine is faster than that of the slowly released Cordyceps militaris extract, which also affects the synergistic effect of the two components.

[0337] According to the comparison between Comparative Example 3 and Example 1, when the wall material of the microcapsule-encapsulated Cordyceps militaris extract is made of polyacrylic acid resin with low carboxylic acid group density and polyacrylic acid group density in a mass ratio of 1:1, the proportion of low carboxylic acid group density polyacrylic acid resin is too large, which leads to a decrease in the dissolution rate of the wall material in the intestinal fluid, and also affects the absorption of Cordyceps militaris extract.

[0338] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been shown above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A Cordyceps militaris and Ganoderma lucidum spore powder composite preparation, characterized in that: The composite preparation is microcapsule-embedded particles, the outer layer of which is a polylactic acid-glycolic acid copolymer film, and the inner layer is composite particles of microcapsule-coated Cordyceps militaris extract and microcapsule-coated Ganoderma lucidum spore powder; Calculated by weight, the composite particles are composed of the following components: 20 parts of microcapsule-coated Cordyceps militaris extract, 30 parts or 35 parts of microcapsule-coated Ganoderma lucidum spore powder and 10 parts of adjuvant; The microcapsules are coated with Cordyceps militaris extract, which are, from outside to inside: an enteric layer and Cordyceps militaris extract; The microcapsules encapsulate the Ganoderma lucidum spore powder, which are, from the outside to the inside: a polymer sustained-release coating and the Ganoderma lucidum spore powder; The materials of the enteric layer are high carboxylic acid group density polyacrylic acid resin and low carboxylic acid group density polyacrylic acid resin; The material of the polymer sustained-release coating is a high carboxylic acid group density polyacrylic acid resin; The high carboxylic acid group density polyacrylic acid resin is Eudragit L; The low carboxylic acid group density polyacrylic acid resin is Eudragit S; The auxiliary agent is β - cyclodextrins; The preparation method of microcapsule coated Cordyceps militaris extract is as follows: S1, dissolving a polyacrylic acid resin with a high carboxylic acid group density and a polyacrylic acid resin with a low carboxylic acid group density in ethyl acetate, and stirring evenly to form a homogeneous polyacrylic acid resin solution; S2, adding the Cordyceps militaris extract to the polyacrylic acid resin solution and stirring evenly; S3, adding emulsifier Tween 80 to form an emulsion; S4, emulsifying the emulsion under high-speed stirring to form stable emulsion particles; S5, adding glutaraldehyde cross-linking agent dropwise into the emulsion to form cross-links between polyacrylic acid resin molecules, thereby forming an enteric layer of the microcapsule; S6, continue to stir the emulsion to allow the cross-linking reaction to proceed fully until stable microcapsules are formed; S7, centrifuging and filtering to separate the microcapsules from the reaction mixture; S8, washing the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and drying to obtain the microcapsule-encapsulated Cordyceps militaris extract; The preparation method of microcapsule coated Ganoderma lucidum spore powder is as follows: A1. dissolving a polyacrylic acid resin having a high carboxylic acid group density in ethyl acetate and stirring the mixture to form a homogeneous polyacrylic acid resin solution; A2, adding the ganoderma lucidum spore powder into the polyacrylic acid resin solution and stirring evenly; A3, adding emulsifier Tween 80 to form an emulsion; A4, emulsifying the emulsion under high-speed stirring to form stable emulsion particles; A5, adding glutaraldehyde cross-linking agent dropwise into the emulsion to form cross-links between polyacrylic acid resin molecules, thereby forming a polymer sustained-release coating of the microcapsules; A6. Continue stirring the emulsion to allow the crosslinking reaction to proceed fully until stable microcapsules are formed; A7, centrifuging and filtering to separate the microcapsules from the reaction mixture; A8, washing the microcapsules to remove unreacted polyacrylic acid resin and other impurities, and drying to obtain microcapsule-encapsulated Ganoderma lucidum spore powder; The preparation method of the composite preparation is as follows: Step 1: mixing the microcapsule-encapsulated Cordyceps militaris extract and the microcapsule-encapsulated Ganoderma lucidum spore powder in proportion; Step 2: Add auxiliary agents and mix well; Step 3: granulate the uniformly mixed materials through a granulator to form composite particles; Step 4: dissolving the polylactic acid-co-glycolic acid in a solvent to form a polylactic acid-co-glycolic acid solution; Step 5: soaking the composite particles in a polylactic acid-co-glycolic acid copolymer solution so that the surface of the composite particles is evenly coated with a layer of polylactic acid-co-glycolic acid copolymer film; Step 6: drying to form the composite preparation; Wherein, in the enteric layer, the mass ratio of the low carboxylic acid group density polyacrylic acid resin to the high carboxylic acid group density polyacrylic acid resin is calculated according to the following formula: ； in, β is the mass ratio of the low carboxylic acid group density polyacrylic acid resin to the high carboxylic acid group density polyacrylic acid resin, and the unit is 1; α Characterizes the ratio of the crosslinking density of the polymer sustained-release coating to the crosslinking density of the enteric layer, the unit is 1, and is calculated based on the ratio of the added amount of the crosslinking agent of the polymer sustained-release coating to the crosslinking agent of the enteric layer; H L is the thickness of the polymer sustained-release coating, in nm; H C is the thickness of the enteric layer in nm; Calculated by weight, the amounts of the crosslinking agent of the polymer sustained-release coating and the crosslinking agent of the enteric layer are: 0.75 parts of glutaraldehyde crosslinking agent and 1.5 parts of glutaraldehyde crosslinking agent, respectively; or the amounts of the cross-linking agent of the polymer sustained-release coating and the cross-linking agent of the enteric layer added are: 0.8 parts of glutaraldehyde cross-linking agent and 1.8 parts of glutaraldehyde cross-linking agent, respectively; or the amounts of the cross-linking agent of the polymer sustained-release coating and the cross-linking agent of the enteric layer added are: 0.8 parts of glutaraldehyde cross-linking agent and 1.2 parts of glutaraldehyde cross-linking agent; The thickness of the polymer coating was 15 nm, and the thickness of the enteric layer was 20 nm; After calculation, the value of β is 0.4, 0.33 or 0.

5.

2. The Cordyceps militaris and Ganoderma lucidum spore powder composite preparation according to claim 1, characterized in that: The particle size of the composite preparation is 45, 50 or 60 μm.

3. The Cordyceps militaris and Ganoderma lucidum spore powder composite preparation according to claim 1, characterized in that: The particle size of the composite particles is 3, 4 or 6 μm.

4. The Cordyceps militaris and Ganoderma lucidum spore powder composite preparation according to claim 1, characterized in that: The particle size of the microcapsule-coated Cordyceps militaris extract is 0.6 or 0.7 μm; the particle size of the microcapsule-coated Ganoderma lucidum spore powder is 0.4 or 0.5 μm.

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