Preparation method of astaxanthin cordyceps sinensis fine powder

Abstract

The application provides a preparation method of astaxanthin cordyceps militaris fine tablets, comprising the following steps: subjecting cordyceps militaris fruiting bodies to supercritical CO2 extraction treatment to separate a cordyceps militaris terpene component; mixing Haematococcus pluvialis powder and edible vegetable oil, adding the cordyceps militaris terpene component and rosemary extract, and cooling and forming to obtain an astaxanthin-cordyceps militaris terpene blend; crushing the residue after extraction, adding purified water and a composite enzyme preparation to perform enzymolysis to obtain an enzymolysis liquid; adding a chitosan quaternary ammonium salt solution, centrifuging after flocculation, vacuum drying, and crushing to obtain cordyceps militaris active powder; mixing and granulating raw materials to obtain granulation particles; uniformly mixing the granulation particles with xylitol and microcrystalline cellulose, and pressing into tablets; and placing the tablets in a coating machine for coating. The application realizes efficient retention of active ingredients, improvement of safety and stability of product quality through the cooperation of multiple technologies such as supercritical CO2 extraction, enzymolysis flocculation, low-temperature fluidized bed granulation and hot melt coating.

Description

Technical Field

[0001] This invention belongs to the field of health food processing technology, specifically relating to a method for preparing astaxanthin cordyceps extract tablets. Background Technology

[0002] The astaxanthin cordyceps extract tablets produced by a certain biotechnology company in Yunnan Province have three technical defects, as detailed below.

[0003] The first issue is the excessive loss of active ingredients during processing. The company's test report shows an actual fat content of only 0.1 grams per 100 grams and an energy value of 1601 kJ per 100 grams, but the product label states a fat content of 9.3 grams per 100 grams and an energy value of 1842 kJ per 100 grams. This discrepancy stems from a technical defect in the current production process, specifically a technical change order requiring the use of an 85% ethanol solution for coating, leading to the dissolution and loss of fat-soluble astaxanthin during the coating stage. Data from the company's laboratory shows that the actual astaxanthin retention rate under this process is only 78% to 82%, far below the internal control standard of 90%.

[0004] Secondly, there's the issue of consumer restriction due to residual allergens from Cordyceps militaris. It's unsuitable for infants, pregnant women, and those with fungal allergies because the Cordyceps militaris powder in the ingredient list on the change order only underwent coarse grinding, failing to effectively remove cordycepin-binding protein, a key allergen. A third-party ELISA test report confirmed that the allergen residue was as high as 12.5 ppm, exceeding the infant food safety threshold of 0.5 ppm by 25 times.

[0005] Thirdly, there is the issue of inaccurate nutritional labeling caused by a failure in the microencapsulation process. The test report shows a protein content of 0.46 grams per 100 grams and a fat content of 0.1 grams per 100 grams, but the theoretical values ​​calculated by the company based on the formula should be no less than 0.6 grams of protein per 100 grams and no less than 0.8 grams of fat per 100 grams. The root cause is that the astaxanthin microcapsule powder in the change order encountered moisture penetration during the fluidized bed granulation stage. When 20% to 30% hydroxypropyl methylcellulose binder was added, the microcapsule wall material swelled, causing astaxanthin leakage and encapsulation, forming a buried structure that cannot be extracted by conventional fat detection solvents.

[0006] The company attempted three improvement plans, all of which failed. The first plan increased the microcapsule wall material concentration from 3.5% to 5.0%, which reduced leakage but resulted in tablet hardness exceeding 120 Newtons and a disintegration time exceeding 30 minutes, violating the company's internal control standard of 15 minutes for disintegration. The second plan replaced the ethanol coating solution with a pure water dispersion system, resulting in cracking of the coating film and a 40% astaxanthin fading rate after 7 days under 3000 lux light. The third plan involved hot air drying of the Cordyceps militaris raw material at 60℃, but HPLC analysis revealed a cordycepin degradation rate exceeding 25%. These technical bottlenecks severely restricted product market expansion. Therefore, a method for preparing astaxanthin Cordyceps militaris tablets needs to be designed. Summary of the Invention

[0007] To overcome the shortcomings of the existing technology, a method for preparing astaxanthin cordyceps extract tablets is provided.

[0008] To achieve the above objectives, the present invention provides the following technical solution:

[0009] A method for preparing astaxanthin cordyceps extract tablets, the method comprising the following steps:

[0010] (1) The fruiting bodies of Cordyceps militaris are subjected to supercritical CO2 extraction to separate Cordyceps militaris terpenoid components. In step (1), the specific parameters of the supercritical CO2 extraction are: extraction pressure of 38-40 MPa, extraction temperature of 48-50℃, CO2 flow rate of 25-30 L / min, and an entrainer is continuously injected at 4.0% to 5.0% of the CO2 flow rate for continuous extraction for 2 to 2.5 hours. The entrainer includes ethyl acetate and edible ethanol, and the ethyl acetate accounts for 5-10% of the volume of the entrainer.

[0011] In the production of astaxanthin and Cordyceps militaris extract tablets, the industry has long faced the challenge of excessive loss of active ingredients during processing. Specifically, this manifests as a significant discrepancy between the actual fat content of the product and the claimed value on the label. The root cause lies in the traditional ethanol coating process, where the ethanol solvent dissolves the fat-soluble astaxanthin, leading to the loss of the active ingredient. Existing technologies typically attempt to alleviate this problem by increasing the microcapsule wall thickness, but this results in new defects such as excessive tablet hardness and prolonged disintegration time. This invention introduces supercritical carbon dioxide extraction technology to process Cordyceps militaris fruiting bodies, selectively separating the Cordyceps militaris terpene component rich in sesquiterpenes. This component acts as a natural stabilizer in subsequent processes, forming a hydrophobic complex structure with astaxanthin molecules to construct a physical barrier on the surface of the active ingredient. This protective mechanism effectively replaces the ethanol solvent system, blocking oxygen penetration at the source and avoiding astaxanthin dissolution loss caused by the coating process.

[0012] (2) Mix Haematococcus pluvialis powder with edible vegetable oil, stir and dissolve at 60-65 °C, add Cordyceps militaris terpene component and rosemary extract obtained in step (1), homogenize and cool and solidify under nitrogen protection to obtain astaxanthin-Cordyceps militaris terpene blend; in step (2), the Haematococcus pluvialis powder and edible vegetable oil are mixed at a mass ratio of 1:2.8-3.2, the amount of Cordyceps militaris terpene component added is 22-25% of the mass of Haematococcus pluvialis powder; the amount of rosemary extract added is 10-15% of the mass of Haematococcus pluvialis powder, and the edible vegetable oil is soybean oil with an acid value ≤0.5mg KOH / g.

[0013] (3) The raffinate after extraction in step (1) is pulverized to 60-80 mesh, and purified water is added at 4-6 times its dry weight. The pH is adjusted to 6.8-7.0, and a compound enzyme preparation is added for enzymatic hydrolysis to obtain the hydrolysate. In step (3), the enzymatic hydrolysis is carried out at 48-50℃ for 1.5-2 hours. The compound enzyme preparation is composed of cellulase and neutral protease in a mass ratio of 1:1-1.2. The amount of the compound enzyme preparation added is 4-6% of the dry weight of the raffinate.

[0014] (4) Add chitosan quaternary ammonium salt solution to the enzymatic hydrolysate obtained in step (3), flocculate and centrifuge to separate the precipitate, and pulverize the precipitate to 400-500 mesh after vacuum drying to obtain Cordyceps militaris active powder; in step (4), the amount of chitosan quaternary ammonium salt added is 0.8-1.0% of the mass of the enzymatic hydrolysate.

[0015] Despite resolving the astaxanthin stability issue, the presence of residual allergens in the Cordyceps militaris raw material still limits the target population for the product. Conventional coarse grinding cannot effectively destroy the tertiary structure of the allergenic proteins in Cordyceps militaris, resulting in excessive levels of cordycepin-binding proteins in the final product. This invention employs a synergistic enzymatic hydrolysis and flocculation treatment on the residue after supercritical extraction: First, through the synergistic catalytic action of cellulase and neutral protease in a near-neutral environment, cellulase specifically degrades the β-glucan network structure of the cell wall, while the neutral protease precisely cleaves the peptide chains of the allergenic proteins; subsequently, the added chitosan quaternary ammonium salt, due to its cationic properties, electrostatically adsorbs the negatively charged protein fragments, forming insoluble flocculated precipitates. This process is carried out under mild conditions, thoroughly removing allergenic components while completely preserving heat-sensitive active substances such as cordycepin and polysaccharides.

[0016] (5) The astaxanthin-cordyceps militaris terpene blend obtained in step (2), the cordyceps militaris active powder obtained in step (4), and the Ganoderma lucidum spore cell wall breaking powder are mixed, and the resulting mixture is granulated by fluidized bed granulation to obtain granulated particles; in step (5), the astaxanthin-cordyceps militaris terpene blend, cordyceps militaris active powder, and Ganoderma lucidum spore cell wall breaking powder are mixed at a mass ratio of 1:(3.9-4.1):(3.8-4.2).

[0017] In step (5), in fluidized bed granulation, the inlet air temperature is 45-50°C, and the added binder is an aqueous solution of hydroxypropyl methylcellulose with a mass fraction of 6-8%, wherein the amount of binder added is 20-25% of the mass of the mixture.

[0018] Once the stability and safety of the active ingredients are guaranteed, new technical challenges arise during production. In existing wet granulation processes, water penetration from the hydroxypropyl methylcellulose binder solution can cause the microcapsule structure to swell and rupture, leading to astaxanthin leakage which is then encapsulated and buried by excipients, resulting in distorted nutrient content detection. This invention addresses this problem through triple regulation: In the material compounding stage, the astaxanthin terpene blend is combined with desensitized Cordyceps militaris active powder and Ganoderma lucidum spore cell-wall-broken powder in a specific ratio, ensuring that the fat-soluble active ingredients and water-soluble components form a complementary system; in the granulation stage, low-temperature fluidized bed granulation is used, with precisely controlled concentrations of hydroxypropyl methylcellulose aqueous solution added as a binder, significantly reducing water osmotic pressure in the low-temperature environment; the β-glucan contained in the Ganoderma lucidum spore cell-wall-broken powder plays a natural binding role in this process, further enhancing the density of the particle structure. These three factors synergistically prevent abnormal encapsulation of the active ingredients.

[0019] (6) The granulated particles obtained in step (5) are mixed evenly with xylitol and microcrystalline cellulose and then pressed into tablets; in step (6), the granulated particles are mixed with xylitol and microcrystalline cellulose at a mass ratio of 100:(32-35):(25-28); the tablets have a hardness of 100-110N and a weight of 0.647-0.653g.

[0020] (7) Place the uncoated tablets obtained in step (6) in a coating machine and coat them with a hot-melt coating agent at a tablet bed temperature of 65-68°C. The coating weight gain is 4.5-5.0% of the uncoated tablet mass. In step (7), the hot-melt coating agent is composed of hydrogenated palm oil, beeswax, and polyethylene glycol 6000 in a mass ratio of 50:(18-20):(20-22).

[0021] As the final protective step in tablet coating, traditional ethanol-based coating not only carries the risk of solvent residue but also results in a coating film prone to cracking under varying humidity levels. This solution employs a hot-melt coating agent system composed of hydrogenated palm oil, beeswax, and polyethylene glycol 6000, applying the coating at a tablet bed temperature of 65-68 degrees Celsius. Within this temperature window, the long-chain molecules of polyethylene glycol 6000 extend and interweave within the gaps in the lipid crystal network, forming a temperature-responsive composite film. This film structure maintains its integrity in the acidic environment of gastric juice, effectively protecting the active ingredient as it passes through the upper digestive tract. Upon entering the alkaline intestinal environment, it rapidly disintegrates under the action of bile salts, achieving precise delivery of the active substance. The entire process completely avoids the use of organic solvents, overcoming the solvent residue and film instability defects of traditional coating processes.

[0022] The core innovation of this application, which runs through the entire production process, lies in the closed-loop utilization strategy of raw materials. By using the Cordyceps militaris terpenoid fraction separated from the same batch of Cordyceps militaris fruiting bodies through supercritical extraction for astaxanthin stabilization treatment, and at the same time converting the extraction residue into desensitizing active powder, the gradient utilization of raw material components is achieved. This design ensures the integrity of the original bioactive spectrum of Cordyceps militaris while avoiding the risk of component incompatibility introduced by exogenous additives.

[0023] In the final product, the terpene soybean oil complex provides physical isolation, the enzymatic hydrolysis and flocculation process ensures biocompatibility, and the hot-melt coating film constructs a delivery control system. Together, these three elements form a multi-layered protection network. This multi-level protection mechanism achieves a balance between shelf-life stability and food safety while maintaining bioavailability, providing a new technological paradigm for the functional food manufacturing field.

[0024] Compared with the prior art, the advantages and beneficial effects of the present invention are as follows:

[0025] 1. This invention utilizes supercritical CO2 extraction technology to process Cordyceps militaris fruiting bodies and then separates the Cordyceps militaris terpene component. This Cordyceps militaris terpene component plays a crucial role in the subsequent preparation of astaxanthin-Cordyceps militaris terpene blends. Its sesquiterpenoid compounds form a complex structure with astaxanthin molecules through hydrophobic interactions, effectively blocking oxygen permeation. This protective mechanism replaces the traditional ethanol coating process, solving the problem of astaxanthin loss due to solvent dissolution.

[0026] 2. In the formation stage of the astaxanthin-cordyceps militaris blend, Haematococcus pluvialis powder and soybean oil are mixed at ratio 1. After adding the cordyceps militaris terpenoid component, molecular-level dispersion is achieved through homogenization. The triglycerides in soybean oil provide a continuous phase matrix, while the cordyceps militaris terpenoid component embeds itself in the intermolecules of astaxanthin, forming steric hindrance. The added rosemary extract contains various phenolic antioxidants that preferentially capture free radicals, forming a dual-stabilizing system with the aforementioned physical barriers. The cooling and molding process under nitrogen protection completely eliminates oxygen interference, ensuring the initial stability of the active ingredients.

[0027] 3. To address the allergen residues from Cordyceps militaris, this invention employs a combined enzymatic hydrolysis-flocculation technology to treat the raffinate after supercritical fluid extraction. Cellulase disrupts the β-glucan structure of the cell wall, and neutral protease cleaves the peptide chains of the allergenic proteins. Subsequently, chitosan quaternary ammonium salt is added, which binds to the carboxyl anions of the proteins through amino cations, forming insoluble flocculants. This process reduces the risk of allergy while fully preserving active ingredients such as cordycepin and polysaccharides.

[0028] 4. In the material compounding stage of this invention, the component ratio is strictly followed: astaxanthin-Cordyceps militaris terpene blend, Cordyceps militaris active powder, and Ganoderma lucidum spore cell-wall broken powder are mixed at a ratio of 1:3.9-4.1:3.8-4.2. This ratio ensures that the water-soluble components of Cordyceps militaris and the fat-soluble active substances form a complementary system, while the β-glucan in the Ganoderma lucidum spore cell-wall broken powder enhances the particle binding force. The fluidized bed granulation process uses a 6-8% hydroxypropyl methylcellulose aqueous solution as a binder, and granulation is completed at a low temperature of 45-50 ℃ to avoid structural damage caused by high temperature and moisture.

[0029] 5. During the coating process, the long-chain molecules of polyethylene glycol 6000 interweave with the gaps between oil crystals, forming a dense but disintegratable membrane structure. This membrane maintains its integrity in the gastric juice environment, but rapidly disintegrates upon entering the intestine due to the action of bile salts, achieving targeted release of the active substance.

[0030] 6. The Cordyceps militaris terpenoids produced in the supercritical extraction process are used to protect astaxanthin, and the remaining material is converted into desensitizing active powder. This design maximizes the preservation of the original active spectrum of Cordyceps militaris and avoids the problem of component incompatibility caused by exogenous addition.

[0031] 7. In the astaxanthin-Cordyceps militaris extract tablets of the present invention, astaxanthin molecules are encapsulated by a terpene-soybean oil complex system, the active ingredients of Cordyceps militaris are desensitized through enzymatic hydrolysis and flocculation, and the hot-melt coating film provides a physicochemical barrier. The three work synergistically to form a multi-layered protective network, achieving a balance between shelf-life stability and food safety while ensuring bioavailability. Detailed Implementation

[0032] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0033] In the specific embodiments of this application, the sources of various main raw materials are briefly described as follows:

[0034] Cordyceps militaris fruiting bodies: purchased from Jiangsu Shenhua Pharmaceutical Co., Ltd., product number YMCC-01.

[0035] Haematococcus pluvialis powder: purchased from Xi'an Tianguangyuan Biotechnology Co., Ltd., with an astaxanthin content of 5%.

[0036] Rosemary extract: purchased from Xi'an Tianyi Biotechnology Co., Ltd., model number TY-MDX, ​​with an active ingredient content of 20%.

[0037] Edible vegetable oil: Grade 1 soybean oil conforming to national standard GB / T 1535, with an acid value ≤0.5mg KOH / g, purchased from COFCO Food Marketing Co., Ltd.

[0038] Ethyl acetate: purchased from Sinopharm Chemical Reagent Co., Ltd., CAS No. 141-78-6, specification: analytical grade.

[0039] Edible ethanol: Purchased from COFCO Biochemical Energy (Zhaodong) Co., Ltd., conforming to GB 31640 standard, food grade.

[0040] Compound enzyme preparation: including cellulase and neutral protease. The cellulase was purchased from Ningxia Heshibi Biotechnology Co., Ltd., with an enzyme activity of 100,000 U / g; the neutral protease was also purchased from Ningxia Heshibi Biotechnology Co., Ltd., with an enzyme activity ≥80,000 U / g.

[0041] Chitosan quaternary ammonium salt: purchased from Jinan Shengquan Group Co., Ltd., model SQ-80, degree of deacetylation ≥80%.

[0042] Ganoderma lucidum spore cell wall broken powder: purchased from Anhui Zhishentang Pharmaceutical Co., Ltd., cell wall broken rate ≥98%.

[0043] Hydroxypropyl methylcellulose: purchased from Huzhou Zhanwang Pharmaceutical Co., Ltd., model E6, viscosity 6 mPa·s.

[0044] Xylitol: Purchased from Shandong Futian Pharmaceutical Co., Ltd., conforming to GB 13509 standard, food grade.

[0045] Microcrystalline cellulose: purchased from Anhui Shanhe Pharmaceutical Excipients Co., Ltd., model number PH-101.

[0046] Hydrogenated palm oil: purchased from Shanghai Kerry Foods Co., Ltd., melting point 60-65℃.

[0047] Beeswax: Purchased from Beijing Fengzhen Technology Development Co., Ltd., conforming to GB 1886.87 standard, food grade.

[0048] Polyethylene glycol 6000: Purchased from Jiangsu Haian Petrochemical Plant, CAS No. 25322-68-3, pharmaceutical grade.

[0049] The technical solution of this application is as follows:

[0050] A method for preparing astaxanthin cordyceps extract tablets, the method comprising the following steps:

[0051] (1) The fruiting bodies of Cordyceps militaris were subjected to supercritical CO2 extraction to separate Cordyceps militaris terpenoid components.

[0052] (2) Mix Haematococcus pluvialis powder with edible vegetable oil, stir and dissolve at 60-65 ℃, add Cordyceps militaris terpene component and rosemary extract obtained in step (1), and after homogenization, cool and solidify under nitrogen protection to obtain astaxanthin-Cordyceps militaris terpene blend.

[0053] (3) Pulverize the raffinate after extraction in step (1) to 60-80 mesh, add 4-6 times its dry weight of purified water, adjust the pH to 6.8-7.0, add compound enzyme preparation for enzymatic hydrolysis to obtain enzymatic hydrolysate;

[0054] (4) Add chitosan quaternary ammonium salt solution to the enzymatic hydrolysate obtained in step (3), flocculate and centrifuge to separate the precipitate, and then pulverize the precipitate to 400-500 mesh after vacuum drying to obtain Cordyceps militaris active powder.

[0055] (5) Mix the astaxanthin-cordyceps militaris terpene blend obtained in step (2), the cordyceps militaris active powder obtained in step (4), and the Ganoderma lucidum spore cell wall breaking powder, and granulate the resulting mixture by fluidized bed granulation to obtain granulated particles.

[0056] (6) The granulated particles obtained in step (5) are mixed evenly with xylitol and microcrystalline cellulose and then pressed into tablets;

[0057] (7) Place the uncoated tablets obtained in step (6) into a coating machine and coat them with a hot melt coating agent at a tablet bed temperature of 65-68°C. The coating weight gain is 4.5-5.0% of the uncoated tablet mass.

[0058] In step (1), the specific parameters of the supercritical CO2 extraction process are: extraction pressure of 38-40 MPa, extraction temperature of 48-50 ℃, CO2 flow rate of 25-30 L / min, and continuous injection of entrainer at 4.0% to 5.0% of the CO2 flow rate, with extraction lasting 2 to 2.5 hours. The entrainer includes ethyl acetate and edible ethanol, with ethyl acetate accounting for 5-10% of the entrainer volume. This scheme achieves selective separation of terpenes and other active ingredients by precisely controlling the physicochemical parameters of supercritical CO2 (pressure 38-40 MPa / temperature 48-50 ℃) and utilizing the polarity difference. Due to the extraction conditions and molecular characteristics, the Cordyceps militaris terpene components obtained in the supercritical CO2 extraction process mainly contain: terpinene, eucalyptol, and gingerene. The active ingredients in the raffinate mainly include cordycepin and polysaccharides.

[0059] In step (2), the Haematococcus pluvialis powder and edible vegetable oil are mixed at a mass ratio of 1:2.8-3.2, the amount of Cordyceps militaris terpene component added is 22-25% of the mass of Haematococcus pluvialis powder, the amount of rosemary extract added is 10-15% of the mass of Haematococcus pluvialis powder, and the edible vegetable oil is soybean oil with an acid value ≤0.5mg KOH / g.

[0060] In step (3), the enzymatic hydrolysis is carried out at 48-50 °C for 1.5-2 hours. The compound enzyme preparation is composed of cellulase and neutral protease in a mass ratio of 1:1-1.2. The amount of the compound enzyme preparation added is 4-6% of the dry weight of the raffinate.

[0061] In step (4), the amount of chitosan quaternary ammonium salt added is 0.8-1.0% of the mass of the enzymatic hydrolysate.

[0062] In step (5), the astaxanthin-cordyceps militaris terpene blend, cordyceps militaris active powder, and Ganoderma lucidum spore cell wall broken powder are mixed at a mass ratio of 1:(3.9-4.1):(3.8-4.2).

[0063] In step (5), in fluidized bed granulation, the inlet air temperature is 45-50°C, and the added binder is an aqueous solution of hydroxypropyl methylcellulose with a mass fraction of 6-8%, wherein the amount of binder added is 20-25% of the mass of the mixture.

[0064] In step (6), the granulated particles are mixed with xylitol and microcrystalline cellulose at a mass ratio of 100:(32-35):(25-28); the hardness of the unprocessed tablets is 100-110N and the tablet weight is 0.647-0.653g.

[0065] In step (7), the hot melt coating agent is composed of hydrogenated palm oil, beeswax, and polyethylene glycol 6000 in a mass ratio of 50:(18-20):(20-22).

[0066] This invention solves three major industry problems simultaneously by combining multiple technologies, including supercritical CO2 extraction, enzymatic hydrolysis and flocculation, low-temperature fluidized bed granulation, and hot melt coating, to address astaxanthin processing loss, Cordyceps militaris allergen residue, and distorted nutrient detection. It achieves a balance between efficient retention of active ingredients, enhanced safety, and effective product quality control.

[0067] The technical solutions of the present invention are further illustrated below through examples and comparative examples, but the scope of protection of the present invention is not limited thereto. Example 1

[0068] The fruiting bodies of Cordyceps militaris were subjected to supercritical CO2 extraction at an extraction pressure of 40 MPa, an extraction temperature of 50 °C, and a CO2 flow rate of 30 L / min. An entrainer was continuously injected at 5.0% of the CO2 flow rate, and extraction was continued for 2.5 hours. The entrainer consisted of 10% by volume ethyl acetate and edible ethanol. The Cordyceps militaris terpenoid fraction was then separated and prepared for use.

[0069] Haematococcus pluvialis powder and soybean oil meeting the acid value requirements were mixed at a mass ratio of 1:3 and stirred at 65 °C to dissolve. The added cordyceps militaris terpenoid component accounted for 25% of the mass of the Haematococcus pluvialis powder, and the added rosemary extract accounted for 15% of the mass of the Haematococcus pluvialis powder. After high-pressure homogenization, the mixture was cooled and shaped under nitrogen protection to obtain an astaxanthin-cordyceps militaris terpenoid blend.

[0070] The raffinate after supercritical extraction was pulverized to 80 mesh, and purified water with 6 times its dry weight was added to adjust the pH to 7.0. A compound enzyme preparation consisting of cellulase and neutral protease in a mass ratio of 1:1.2 was added at 6% of the dry weight of the raffinate. The mixture was enzymatically hydrolyzed at 50 °C for 2 hours to obtain the enzymatic hydrolysate.

[0071] Chitosan quaternary ammonium salt solution was added to the enzymatic hydrolysate at a concentration of 1.0% of the hydrolysate mass. After flocculation, the precipitate was separated by centrifugation. The precipitate was then vacuum dried and pulverized to 500 mesh to obtain Cordyceps militaris active powder.

[0072] Astaxanthin-Cordyceps militaris terpene blend, Cordyceps militaris active powder, and Ganoderma lucidum spore cell wall-breaking powder were mixed at a mass ratio of 1:4.1:4 and granulated using a fluidized bed. The inlet air temperature was set to 50 ℃. Hydroxypropyl methylcellulose aqueous solution with a mass fraction of 8% was added as a binder at a mass ratio of 25% of the mixture to obtain granulated particles.

[0073] Granulated granules were mixed evenly with xylitol and microcrystalline cellulose at a mass ratio of 100:35:28 and then compressed into uncoated tablets. The tablet hardness was controlled at 110 N and the tablet weight at 0.653 g. The uncoated tablets were placed in a coating machine and coated with a hot-melt coating agent composed of hydrogenated palm oil, beeswax, and polyethylene glycol 6000 at a mass ratio of 50:20:22 at a tablet bed temperature of 68 ℃. The coating weight gain was controlled at 5.0% of the uncoated tablet weight, finally obtaining astaxanthin cordyceps extract tablets. Example 2

[0074] In this embodiment, the similarities to those in Embodiment 1 will not be repeated, and the differences are as follows:

[0075] The fruiting bodies of Cordyceps militaris were subjected to supercritical CO2 extraction at an extraction pressure of 38 MPa, an extraction temperature of 48℃, and a CO2 flow rate of 25 L / min. An entrainer was continuously injected at 4.0% of the CO2 flow rate, and extraction was continued for 2 hours. The entrainer consisted of 5% by volume ethyl acetate and edible ethanol. The Cordyceps militaris terpenoid fraction was then separated and prepared for use.

[0076] Haematococcus pluvialis powder and soybean oil meeting the acid value requirements were mixed at a mass ratio of 1:2.8 and stirred and dissolved at 60 °C. The added cordyceps militaris terpenoid component accounted for 22% of the mass of the Haematococcus pluvialis powder, and the added rosemary extract accounted for 10% of the mass of the Haematococcus pluvialis powder. After high-pressure homogenization, the mixture was cooled and shaped under nitrogen protection to obtain an astaxanthin-cordyceps militaris terpenoid blend.

[0077] The raffinate after supercritical extraction was pulverized to 60 mesh, and purified water with 4 times its dry weight was added to adjust the pH to 6.8. A compound enzyme preparation consisting of cellulase and neutral protease in a 1:1 mass ratio was added at 4% of the dry weight of the raffinate. The mixture was enzymatically hydrolyzed at 48 °C for 1.5 hours to obtain the enzymatic hydrolysate.

[0078] Chitosan quaternary ammonium salt solution was added to the enzymatic hydrolysate at a concentration of 0.8% of the hydrolysate mass. After flocculation, the precipitate was separated by centrifugation. The precipitate was then vacuum dried and pulverized to 400 mesh to obtain Cordyceps militaris active powder.

[0079] Astaxanthin-Cordyceps militaris terpene blend, Cordyceps militaris active powder, and Ganoderma lucidum spore cell wall-breaking powder were mixed at a mass ratio of 1:3.9:3.8 and granulated using a fluidized bed. The inlet air temperature was set to 45 ℃. A 6% (w / w) aqueous solution of hydroxypropyl methylcellulose was added as a binder at a mass ratio of 20% of the mixture to obtain granulated particles.

[0080] Granulated granules were mixed evenly with xylitol and microcrystalline cellulose at a mass ratio of 100:32:25 and then compressed into uncoated tablets. The tablet hardness was controlled at 100 N and the tablet weight at 0.647 g. The uncoated tablets were placed in a coating machine and coated with a hot-melt coating agent composed of hydrogenated palm oil, beeswax, and polyethylene glycol 6000 at a mass ratio of 50:18:20 at a tablet bed temperature of 65 ℃. The coating weight gain was controlled at 4.5% of the uncoated tablet weight, finally obtaining astaxanthin cordyceps extract tablets. Example 3

[0081] In this embodiment, the similarities to those in Embodiment 1 will not be repeated, and the differences are as follows:

[0082] The fruiting bodies of Cordyceps militaris were subjected to supercritical CO2 extraction at an extraction pressure of 39 MPa, an extraction temperature of 49 °C, and a CO2 flow rate of 27 L / min. An entrainer was continuously injected at 4.5% of the CO2 flow rate, and extraction was continued for 2.2 hours. The entrainer consisted of 7% by volume ethyl acetate and edible ethanol. The Cordyceps militaris terpenoid fraction was then separated and prepared for use.

[0083] Haematococcus pluvialis powder and soybean oil meeting the acid value requirements were mixed at a mass ratio of 1:3 and stirred at 63 °C to dissolve. The added cordyceps militaris terpenoid component accounted for 23% of the mass of the Haematococcus pluvialis powder, and the added rosemary extract accounted for 12% of the mass of the Haematococcus pluvialis powder. After high-pressure homogenization, the mixture was cooled and shaped under nitrogen protection to obtain an astaxanthin-cordyceps militaris terpenoid blend.

[0084] The raffinate after supercritical extraction was pulverized to 70 mesh, and purified water with 5 times its dry weight was added to adjust the pH to 6.9. A compound enzyme preparation consisting of cellulase and neutral protease in a mass ratio of 1:1.1 was added at a rate of 5% of the dry weight of the raffinate. The mixture was enzymatically hydrolyzed at 49 °C for 1.8 hours to obtain the enzymatic hydrolysate.

[0085] Chitosan quaternary ammonium salt solution was added to the enzymatic hydrolysate at a concentration of 0.9% of the hydrolysate mass. After flocculation, the precipitate was separated by centrifugation. The precipitate was then vacuum dried and pulverized to 450 mesh to obtain Cordyceps militaris active powder.

[0086] Astaxanthin-Cordyceps militaris terpene blend, Cordyceps militaris active powder, and Ganoderma lucidum spore cell wall-breaking powder were mixed at a mass ratio of 1:4:4 and granulated using a fluidized bed. The inlet air temperature was set to 47 ℃. A 7% (w / w) aqueous solution of hydroxypropyl methylcellulose was added as a binder at a mass ratio of 22% of the mixture to obtain granulated particles.

[0087] Granulated granules were mixed evenly with xylitol and microcrystalline cellulose at a mass ratio of 100:33:26 and then compressed into uncoated tablets. The tablet hardness was controlled at 105 N and the tablet weight at 0.650 g. The uncoated tablets were placed in a coating machine and coated with a hot-melt coating agent composed of hydrogenated palm oil, beeswax, and polyethylene glycol 6000 at a mass ratio of 50:19:21 at a tablet bed temperature of 67 ℃. The coating weight gain was controlled at 4.8% of the uncoated tablet weight, finally obtaining astaxanthin cordyceps extract tablets. Comparative Example 1

[0088] Comparative Example 1 is basically the same as Example 1, except that the supercritical CO2 extraction step was omitted, the Cordyceps militaris terpene component was not used, and the astaxanthin blend only contained Haematococcus pluvialis powder, soybean oil and rosemary extract. Comparative Example 2

[0089] Comparative Example 2 is basically the same as Example 2, except that chitosan quaternary ammonium salt was not used for flocculation treatment in step four, and the enzymatic hydrolysate was directly centrifuged and dried. Comparative Example 3

[0090] Comparative Example 3 is basically the same as Example 3, except that in step seven, an 85% ethanol solution is used as the coating solvent, and the coating weight gain is controlled within the same range as in Example 3. Comparative Example 4

[0091] Comparative Example 4 is basically the same as Example 1, except that in the fluidized bed granulation process in step five, the inlet air temperature is increased to 65 °C and the amount of the binder hydroxypropyl methylcellulose aqueous solution added is increased to 30% of the mass of the mixture. Comparative Example 5

[0092] This comparative example was prepared using a traditional process, with other parameters basically the same as in Example 1, except as follows: Cordyceps militaris fruiting bodies were directly pulverized to 80 mesh to obtain Cordyceps militaris powder. Haematococcus pluvialis powder and soybean oil were mixed at a mass ratio of 1:3 and homogenized. No Cordyceps militaris terpenes or rosemary extract were added. The Cordyceps militaris powder, the Haematococcus pluvialis mixture, and Ganoderma lucidum spore powder were mixed in the same proportion and then granulated using high-temperature boiling with an inlet air temperature of 70°C. An 8% (w / w) aqueous solution of hydroxypropyl methylcellulose was used as a binder, with an addition amount of 30%. After tableting, the tablets were coated with an 85% ethanol solution, resulting in a 5% weight gain.

[0093] Performance Test Results and Analysis

[0094] Astaxanthin Cordyceps militaris extract tablets were prepared according to the parameters of the examples and comparative examples, respectively. The performance of the obtained products was tested, and the test results are shown in Table 1.

[0095] Analysis of the test results shows that the astaxanthin Cordyceps militaris extract tablets prepared in the three embodiments of this invention exhibit significant advantages in key performance indicators. Regarding the retention of active ingredients, the astaxanthin retention rate of the products in these embodiments is all above 93%, a result far superior to the approximately 80% level of Comparative Examples 1, 3, 4, and 5. This difference mainly stems from the antioxidant protection system synergistically constructed by the Cordyceps militaris terpene component obtained through supercritical CO2 extraction and the rosemary extract. The sesquiterpenoids in the Cordyceps militaris terpene component form a hydrophobic complex with astaxanthin molecules, creating a physical barrier on the surface of the active ingredient and effectively blocking oxygen penetration. Comparative Example 1, lacking the Cordyceps militaris terpene component, has an incomplete antioxidant protection system, leading to more easily degraded astaxanthin during processing and storage, a lower retention rate, and a light fading rate as high as 25.6%. Comparative Example 3 and Comparative Example 5, which used a traditional process, both employed an ethanol coating process. The dissolving effect of ethanol solvent on fat-soluble astaxanthin led to a significant loss of active ingredients during the coating process, with retention rates dropping to 79.8% and 81.2%, respectively. In addition, the ethanol-coated films exhibited poor stability under light, with fading rates as high as 41.2% and 39.5%, respectively.

[0096] Table 1 Analysis of Test Results

[0097]

[0098] Regarding allergen control, the residual allergen levels in the products of the examples were all below the safety threshold of 0.5 ppm, confirming the effectiveness of the enzymatic hydrolysis-flocculation combined technology. In this invention, cellulase specifically degrades the β-glucan network structure of the cell wall, and neutral protease precisely cleaves the peptide chains of allergenic proteins. Subsequently, the added chitosan quaternary ammonium salt, through its cationic properties, electrostatically adsorbs the negatively charged protein fragments, forming insoluble flocculated precipitates. Comparative Example 2, due to the omission of the chitosan quaternary ammonium salt flocculation step, failed to effectively remove the enzymatically hydrolyzed protein fragments, resulting in allergen residues as high as 11.8 ppm. Comparative Example 5, employing a traditional pulverization process, completely lacks targeted allergen removal methods, resulting in allergen residues as high as 12.3 ppm, fully demonstrating the advanced nature of the process in this invention.

[0099] Regarding the accuracy of nutritional component testing, the fat and protein values ​​of the products in the examples highly matched the theoretical formula values, with fat values ​​around 9.2 g / 100 g and protein values ​​around 0.6 g / 100 g. This indicates that the fluidized bed low-temperature granulation process and specific binder control system used in this invention successfully prevented abnormal encapsulation and burial of active ingredients. In Comparative Example 4, due to increased granulation temperature and binder dosage, the microcapsule structure was damaged, and the leaked active ingredients were encapsulated by excipients, resulting in severely distorted fat and protein values, which were only 0.7 g / 100 g and 0.48 g / 100 g, respectively. Comparative Examples 3 and 5 also exhibited similar distorted value problems due to their respective process defects, with fat values ​​of only 0.3 g / 100 g and 0.2 g / 100 g, respectively.

[0100] Regarding product disintegration performance, the disintegration time of all products in the examples was within 13 minutes, meeting internal control standards. However, Comparative Example 4, due to improper granulation process resulting in excessively hard particles, had a disintegration time extended to 28.5 minutes. Comparative Example 5, using high-temperature boiling granulation, achieved a disintegration time of 31.8 minutes, failing to meet the requirements for rapid release. The interpenetration of polyethylene glycol 6000 long-chain molecules in the hot-melt coating agent within the oil crystal network forms a smart membrane structure that is stable in gastric juice and rapidly disintegrates in intestinal juice. This characteristic ensures the precise delivery of the active ingredient.

[0101] In summary, this invention successfully addresses all three technical deficiencies mentioned in the background art through the synergistic effect of four key technological innovations: supercritical extraction to separate Cordyceps militaris terpenoid components and construct a protective system; enzymatic hydrolysis and flocculation to remove allergens; low-temperature fluidized bed granulation to maintain component integrity; and hot-melt coating as a substitute for ethanol coating. The test data perfectly match the claimed beneficial effects, demonstrating the advanced nature, reliability, and practicality of the process in this invention.

[0102] The above description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing astaxanthin cordyceps extract tablets, characterized in that, The preparation method includes the following steps: (1) The fruiting bodies of Cordyceps militaris were subjected to supercritical CO2 extraction to separate Cordyceps militaris terpenoid components. (2) Mix Haematococcus pluvialis powder and edible vegetable oil at a mass ratio of 1:2.8-3.2, stir and dissolve at 60-65 ℃, add the Cordyceps militaris terpene component and rosemary extract obtained in step (1), wherein the amount of Cordyceps militaris terpene component added is 23-25% of the mass of Haematococcus pluvialis powder; the amount of rosemary extract added is 10-15% of the mass of Haematococcus pluvialis powder, after homogenization treatment, cool and solidify under nitrogen protection to obtain astaxanthin-Cordyceps militaris terpene blend; (3) The raffinate after extraction in step (1) is pulverized to 60-80 mesh, and purified water is added at 4-6 times its dry weight. The pH is adjusted to 6.8-7.0, and a compound enzyme preparation is added for enzymatic hydrolysis to obtain the hydrolysate. The compound enzyme preparation is composed of cellulase and neutral protease in a mass ratio of 1:1-1.

2. The amount of the compound enzyme preparation added is 4-6% of the dry weight of the raffinate. (4) Add chitosan quaternary ammonium salt solution to the enzymatic hydrolysate obtained in step (3), wherein the amount of chitosan quaternary ammonium salt added is 0.8-1.0% of the mass of the enzymatic hydrolysate. After flocculation, centrifuge to separate the precipitate. After vacuum drying, the precipitate is pulverized to 400-500 mesh to obtain Cordyceps militaris active powder. (5) The astaxanthin-cordyceps militaris terpene blend obtained in step (2), the cordyceps militaris active powder obtained in step (4), and the Ganoderma lucidum spore cell wall breaking powder are mixed. The resulting mixture is granulated by fluidized bed granulation to obtain granules. The air inlet temperature is 45-50℃. The added binder is a 6-8% hydroxypropyl methylcellulose aqueous solution. The amount of the binder added is 20-25% of the mass of the mixture. The astaxanthin-cordyceps militaris terpene blend, cordyceps militaris active powder, and Ganoderma lucidum spore cell wall breaking powder are mixed at a mass ratio of 1:(3.9-4.1):(3.8-4.2). (6) The granulated particles obtained in step (5) are mixed evenly with xylitol and microcrystalline cellulose and then pressed into tablets; (7) Place the uncoated tablets obtained in step (6) in a coating machine and coat them with a hot melt coating agent at a tablet bed temperature of 65-68°C. The coating weight gain is 4.5-5.0% of the uncoated tablet weight. The hot melt coating agent is composed of hydrogenated palm oil, beeswax, and polyethylene glycol 6000 in a mass ratio of 50:(19-20):(20-21).

2. The method for preparing astaxanthin cordyceps extract tablets according to claim 1, characterized in that, In step (1), the specific parameters of the supercritical CO2 extraction process are: extraction pressure of 38-40 MPa, extraction temperature of 48-50 ℃, CO2 flow rate of 25-30 L / min, and entrainer continuously injected at 4.0% to 5.0% of CO2 flow rate, and extraction continued for 2 to 2.5 hours.

3. The method for preparing astaxanthin cordyceps extract tablets according to claim 2, characterized in that, The entrainer includes ethyl acetate and edible ethanol, wherein the ethyl acetate accounts for 5-10% of the volume of the entrainer.

4. The method for preparing astaxanthin cordyceps extract tablets according to claim 1, characterized in that, In step (2), the edible vegetable oil is soybean oil with an acid value ≤ 0.5 mg KOH / g.

5. The method for preparing astaxanthin cordyceps extract tablets according to claim 1, characterized in that, In step (3), the enzymatic hydrolysis is carried out at 48-50 °C for 1.5-2 hours.

6. The method for preparing astaxanthin cordyceps extract tablets according to claim 1, characterized in that, In step (6), the granulated particles are mixed with xylitol and microcrystalline cellulose at a mass ratio of 100:(32-35):(25-28); the hardness of the unprocessed tablets is 100-110N and the tablet weight is 0.647-0.653g.

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