High-activity cordyceps sinensis and aconite and rhubarb compound health-care preparation and preparation method thereof

Abstract

This invention discloses a highly active compound health supplement made from Cordyceps sinensis, Artemisia argyi, and rhubarb, and its preparation method, belonging to the field of health food and pharmaceutical preparation processing technology. The method includes: adding artificial Cordyceps sinensis ultrafine powder, prepared Rhubarb tanguticum fine powder, Artemisia argyi leaf extract, microcrystalline cellulose PH102, and maltodextrin into a mixer and premixing at 25-35 rpm to allow the powder to adhere to the surface of the excipients; after tableting, the tablets are subjected to ultra-high pressure treatment at 350-380 MPa. This invention achieves uniform distribution and performance optimization of the formulation components without damaging the activity of heat-sensitive components through precise coupling of premixing strength and ultra-high pressure modification parameters. Experiments show that the obtained formulation has an adenosine retention rate ≥96%, a dissolution rate ≥85% after 5 minutes, and excellent moisture resistance and mechanical strength, solving the technical problems of large activity loss, easy moisture absorption, and slow dissolution in traditional formulations.

Description

Technical Field

[0001] This invention belongs to the field of health food and pharmaceutical preparation processing technology, specifically, it relates to a highly active Cordyceps sinensis, Artemisia argyi, and Rhubarb compound health preparation and its preparation method. Background Technology

[0002] Artificially produced Cordyceps sinensis, Tangut rhubarb, and Tibetan Artemisia argyi, as natural products with extremely high nutritional value and medicinal potential, have been widely used in the health food and pharmaceutical fields. In existing compound preparation processing techniques, the medicinal materials are typically pulverized into fine powder or processed into extracts, then mixed with conventional excipients such as microcrystalline cellulose and maltodextrin, and subsequently compressed into tablets using a tablet press. To meet microbial limit requirements, the finished product often requires final sterilization, such as using a moist heat sterilization process at 121°C.

[0003] However, traditional processing techniques have significant technical limitations when handling such compound ingredients. First, the core active ingredients in artificially cultivated Cordyceps sinensis (such as adenosine) are extremely heat-sensitive, readily undergoing thermal degradation and oxidative decomposition under traditional high-temperature sterilization conditions. This results in a significant decrease in the retention rate of active ingredients in the finished product, severely weakening the health benefits of the formulation. This heat damage not only reduces the product's bioactivity but may also generate complex degradation products, increasing the risk of product quality fluctuations.

[0004] Secondly, with the development of preparation technology, medicinal materials are often processed into ultrafine powders to improve bioavailability. However, ultrafine powders have extremely high specific surface area and surface energy, making them prone to self-aggregation during conventional mixing processes, forming tiny powder clusters. Traditional mixing equipment, at normal speeds, often struggles to provide sufficient shear force to break up these physical agglomerations, resulting in uneven distribution of powders of different densities in the compound system. This not only affects the uniformity of the formulation content but may also cause localized stress concentration during tableting, leading to physical defects such as tablet cracking, uneven hardness, or excessive brittleness.

[0005] Furthermore, extracts such as Artemisia argyi have strong hygroscopic properties, easily absorbing moisture from the environment during storage, leading to tablet softening, discoloration, and even mold growth. While increasing compression pressure or the proportion of hydrophobic excipients can enhance moisture resistance to some extent, this often results in an overly dense tablet skeleton, making it difficult for the dissolution medium to penetrate into the formulation, thus significantly reducing the dissolution rate of the active ingredient. This contradiction between dissolution performance and moisture resistance stability makes it difficult for traditional processes to achieve rapid release of the active ingredient while ensuring the physical stability of the product.

[0006] Therefore, developing a preparation process that can protect the activity of heat-sensitive components, achieve highly uniform powder distribution, and simultaneously optimize dissolution and moisture-proof properties has become a technical bottleneck that urgently needs to be overcome in this field. Summary of the Invention

[0007] To address the problems of significant loss of heat-sensitive components, uneven powder distribution, slow dissolution, and hygroscopicity in existing technologies, this invention provides a highly active compound health supplement made from Cordyceps militaris, Artemisia argyi, and rhubarb, along with its preparation method. By coupling a premixing process of specific intensity with ultra-high pressure physical modification technology, a comprehensive improvement in the quality of the preparation is achieved.

[0008] To achieve the above-mentioned objectives, the present invention adopts the following technical solution:

[0009] A method for preparing a highly active compound health supplement containing Cordyceps militaris, Artemisia argyi, and Rhubarb includes the following steps:

[0010] (1) Premixing: Artificial Cordyceps sinensis ultrafine powder, prepared Tangut rhubarb fine powder, Tibetan Artemisia argyi extract, microcrystalline cellulose PH102, maltodextrin, and low-substituted hydroxypropyl cellulose are put into a three-dimensional motion mixer and mixed at a speed that allows the ultrafine powder to be fully dispersed and adsorbed on the surface of the excipients.

[0011] (2) Formulation: Add magnesium stearate and silicon dioxide to the mixture obtained in step (1), mix evenly, and then compress into tablets;

[0012] (3) Ultra-high pressure treatment: After sealing the tablets, place them in an ultra-high pressure treatment chamber and treat them under pressure that can physically modify the tablet structure and improve its overall performance.

[0013] Further, in step (1), the rotation speed is 25-35 rpm and the mixing time is 25-35 minutes.

[0014] Furthermore, in step (3), the pressure is 350-380 MPa, the temperature of the ultra-high pressure treatment is 20-25℃, and the constant pressure holding time is 50-70 minutes.

[0015] Furthermore, in step (3), the pressurization rate in the ultra-high pressure treatment chamber is 60 MPa / min, and the depressurization rate is 40 MPa / min.

[0016] Further, the weight parts of each component in the preparation are as follows: 12-18 parts of artificial Cordyceps sinensis ultrafine powder, 2-4 parts of prepared Tangut rhubarb fine powder, 6-10 parts of Tibetan Artemisia argyi extract, 22-28 parts of microcrystalline cellulose PH102, 18-22 parts of maltodextrin, 6-10 parts of low-substituted hydroxypropyl cellulose, 1-2 parts of magnesium stearate, and 0.5-1.5 parts of silicon dioxide.

[0017] Furthermore, the weight ratio of microcrystalline cellulose PH102 to maltodextrin in the excipients is 1.2-1.3:1.

[0018] Furthermore, the particle size of the artificial Cordyceps sinensis ultrafine powder in step (1) is 500-800 mesh, and it is prepared by the following method: after drying the artificial Cordyceps sinensis to a moisture content of ≤7%, it is subjected to deep cold airflow pulverization. During the pulverization process, the temperature of the pulverization chamber is maintained below -100℃, the pulverization pressure is set to 0.7-0.8 MPa, and the feeding speed is 5-10 kg / h.

[0019] Furthermore, the Tangut rhubarb powder prepared in step (1) is a 100-mesh fine powder prepared by wine stewing.

[0020] Further, the Tibetan Artemisia leaf extract in step (1) is an extract powder obtained by reflux extraction with 75% ethanol and spray drying.

[0021] The present invention also provides a highly active compound health care preparation of Cordyceps sinensis, Artemisia argyi, and rhubarb, which is prepared by the above method.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] (1) This invention uses ultra-high pressure physical modification technology to replace the traditional high-temperature sterilization process. Utilizing the uniformity and instantaneous nature of pressure transmission in a liquid medium, sterilization can be achieved at room temperature or near room temperature. This treatment method effectively avoids the risk of thermal degradation of heat-sensitive components such as adenosine in artificially produced Cordyceps sinensis at high temperatures. Experimental results show that the adenosine retention rate in the preparation obtained by this process is significantly better than that of traditional heat treatment processes, ensuring the bioactivity and efficacy stability of the health care preparation.

[0024] (2) By precisely limiting the premixing speed (25-35 rpm), this invention effectively overcomes the self-aggregation phenomenon of ultrafine powders due to their high surface energy by utilizing the moderate shear force generated by the three-dimensional composite motion. This speed range enables the ultrafine powders to form a uniform physical adsorption state on the surface of the excipient particles, avoiding uneven mixing caused by excessively low speed or centrifugal segregation caused by excessively high speed. The highly uniform powder distribution not only improves the content uniformity of the formulation but also lays the foundation for the synchronous evolution of the structure during subsequent pressure modification.

[0025] (3) This invention utilizes a specific pressure range of 350-380 MPa to generate extremely strong physical bonding between the uniformly distributed ultrafine powder and the excipient components. This bonding state achieves dual functional optimization: on the one hand, the specific proportion of excipient components effectively shields the active ingredient under pressure, significantly reducing the moisture absorption and weight gain rate of the formulation in the storage environment; on the other hand, this process ensures that the formulation maintains high permeability when in contact with the dissolution medium, enabling the active ingredient to be released rapidly. Experiments show that the formulation of this invention, while possessing excellent moisture resistance, can still maintain a high cumulative dissolution rate within 5 minutes, solving the technical problem of slow dissolution of high-density formulations.

[0026] (4) Through ultra-high pressure treatment, the binding tightness between the components of the preparation prepared by this invention is significantly enhanced, thereby improving the overall integrity of the preparation. The resulting tablets maintain low brittleness while significantly increasing hardness. This improvement in mechanical properties not only enhances the impact resistance of the preparation during packaging and transportation, reducing breakage and pulverization, but also significantly improves the process adaptability of the preparation on automated packaging production lines, effectively reducing material loss and production costs. Detailed Implementation

[0027] To enable those skilled in the art to better understand the technical solutions of this invention, the following will provide a more detailed description of this application in conjunction with embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Unless otherwise specified, the raw materials used in this invention are all commercially available conventional products; the technical means used, unless otherwise specified, are all conventional means well known to those skilled in the art.

[0028] Example 1: Preparation of artificially produced Cordyceps sinensis ultrafine powder

[0029] Artificial Cordyceps sinensis was placed in a low-temperature vacuum drying oven at a temperature of 30-40℃ and a vacuum level of -0.08-0.09 MPa until the moisture content was ≤7%. The dried Cordyceps sinensis was then placed in a cryogenic airflow mill, and liquid nitrogen was introduced to maintain the milling chamber temperature at -150℃. This utilizes the low-temperature brittleness to achieve efficient milling and protect the bioactive components. The airflow milling pressure was set to 0.7-0.8 MPa, and the feed rate was controlled at 5-10 kg / h. Through high-frequency collision and shearing, 500-800 mesh artificial Cordyceps sinensis ultrafine powder was obtained and sealed for later use.

[0030] Example 2: Preparation of Tangut Rhubarb Fine Powder (Wine Stewing Method)

[0031] Take Tangut rhubarb, remove impurities, wash and thoroughly moisten it, and cut it into thin slices 2-4 mm thick. Mix it with 12 kg of rice wine per 100 kg of rhubarb, place it in a sealed stewing pot, and simmer over low heat for 4-6 hours until the rhubarb turns dark brown inside and out. After removing it, dry it in a 50℃ constant temperature oven, then pulverize it using a universal grinder and pass it through a 100-mesh sieve to obtain fine Tangut rhubarb powder for later use.

[0032] Example 3: Preparation of Artemisia argyi leaf extract

[0033] Take Artemisia argyi leaves, add 8 times the amount of 75% ethanol, and reflux extract twice at 55℃, 1.5 hours each time. Combine the two extracts and filter through a 200-mesh filter. Concentrate the filtrate under reduced pressure at 65℃ and a vacuum of -0.07 MPa until the relative density of the clear extract reaches 1.15-1.20 (measured at 60℃). Spray dry the clear extract, setting the inlet air temperature to 155℃ and the outlet air temperature to 80℃. Collect the dried powder and seal for later use.

[0034] Example 4

[0035] 1. Weighing materials

[0036] Weigh out 12 kg of artificial Cordyceps sinensis ultrafine powder, 2 kg of prepared Tangut rhubarb fine powder, 6 kg of Tibetan Artemisia argyi extract, 22 kg of microcrystalline cellulose PH102, 18 kg of maltodextrin, 6 kg of low-substituted hydroxypropyl cellulose, 1 kg of magnesium stearate, and 0.5 kg of silicon dioxide.

[0037] 5. Operating Procedures

[0038] (1) Premixing

[0039] The weighed Cordyceps ultrafine powder, rhubarb fine powder, Artemisia argyi extract, microcrystalline cellulose PH102, maltodextrin, and low-substituted hydroxypropyl cellulose were sequentially added to a three-dimensional motion mixer (SYH series). The machine speed was set to 25 rpm, and the mixing time was 25 minutes. During this process, the shear force generated by the three-dimensional composite motion acts on the ultrafine powder, causing it to form a preliminary physical adsorption layer on the surface of the microcrystalline cellulose PH102 particles and the edges of the fiber micropores.

[0040] (2) Formulation:

[0041] Add magnesium stearate and silicon dioxide to the mixer, set the speed to 15 rpm, and continue mixing for 5 minutes. Transfer the well-mixed material to a fully automatic rotary tablet press, set the pressure to 60 kN, and press it into round tablets with a diameter of 9 mm.

[0042] (3) Pressure-induced modification and sterilization

[0043] The compressed tablets were sealed in aluminum-plastic packaging and then placed in an ultra-high pressure processing chamber. Deionized water was used as the pressure transmission medium, and the pressure was increased to 350 MPa at a rate of 60 MPa / min. The pressure was then maintained at a constant pressure of 20°C for 50 minutes. After processing, the pressure was released slowly to atmospheric pressure at a rate of 40 MPa / min, and the finished product was removed.

[0044] Example 5

[0045] 1. Material weighing: 18kg of artificial Cordyceps sinensis ultrafine powder, 4kg of prepared Tangut rhubarb fine powder, 10kg of Tibetan Artemisia argyi extract, 28kg of microcrystalline cellulose PH102, 22kg of maltodextrin, 10kg of low-substituted hydroxypropyl cellulose, 2kg of magnesium stearate, and 1.5kg of silicon dioxide.

[0046] 2. Operation steps: Same as in Example 4, except that: in step (1), the mixing speed is set to 35 rpm and the mixing time is 35 minutes; in step (3), the ultra-high pressure is set to 380 MPa, the processing temperature is 25℃, and the constant pressure is maintained for 70 minutes.

[0047] Example 6

[0048] 1. Material weighing: 15kg of artificial Cordyceps sinensis ultrafine powder, 3kg of prepared Tangut rhubarb fine powder, 8kg of Tibetan Artemisia argyi extract, 25kg of microcrystalline cellulose PH102, 20kg of maltodextrin, 8kg of low-substituted hydroxypropyl cellulose, 1.5kg of magnesium stearate, and 1.0kg of silicon dioxide.

[0049] 2. Operation steps: Same as in Example 4, except that: in step (1), the mixing speed is set to 30 rpm and the mixing time is 30 minutes; in step (3), the ultra-high pressure is set to 365 MPa, the processing temperature is 22℃, and the constant pressure is maintained for 60 minutes.

[0050] Comparative Example 1

[0051] 1. Material weighing: Same as in Example 6.

[0052] 2. Operation steps: Same as in Example 6, except that step (3) does not use ultra-high pressure treatment, but instead places the packaged tablets in a moist heat sterilizer and sterilizes them at 121°C for 20 minutes.

[0053] Comparative Example 2

[0054] 1. Material weighing: 15 kg of microcrystalline cellulose PH102 and 30 kg of maltodextrin (i.e., the weight ratio of microcrystalline cellulose to maltodextrin is 0.5:1). The other components and dosages are the same as in Example 6.

[0055] 2. Operation steps: Same as in Example 6.

[0056] Comparative Example 3

[0057] 1. Material weighing: Same as in Example 6.

[0058] 2. Operation steps: Same as in Example 6, except that step 3 does not involve ultra-high pressure treatment and is directly used as the finished product.

[0059] Comparative Example 4

[0060] 1. Material weighing: Replace microcrystalline cellulose PH102 with ordinary grade microcrystalline cellulose PH101, and the remaining components and dosages are the same as in Example 6.

[0061] 2. Operating steps:

[0062] Comparative Example 5

[0063] 1. Material weighing: Same as in Example 6.

[0064] 2. Operation steps: Same as in Example 6, except that the mixing speed is set to 10 rpm in step (1).

[0065] Comparative Example 6

[0066] 1. Material weighing: Same as in Example 6.

[0067] 2. Operation steps: Same as in Example 6, except that the mixing speed is set to 60 rpm in step (1).

[0068] Data Analysis and Comparison

[0069] To objectively evaluate the technical effects of the present invention, a full-sample comparative test was conducted on the samples prepared in Examples 4-6 and Comparative Examples 1-6. The specific test methods are as follows.

[0070] 1. Adenosine retention rate: Determined by high-performance liquid chromatography (HPLC). Chromatographic conditions: octadecylsilane-bonded silica column (4.6 mm × 250 mm, 5 μm), methanol-water (15:85) as mobile phase, detection wavelength 260 nm. Appropriate amounts of the broken tablets before and after treatment were accurately weighed, extracted ultrasonically, filtered through a membrane, and then injected for analysis. The percentage of adenosine content after treatment relative to the initial content was calculated to evaluate the degree of protection of the heat-sensitive component activity by the process.

[0071] 2. Adenosine dissolution rate: Take appropriate amounts of each group of tablets and use 900 mL of distilled water as the dissolution medium. Set the rotation speed to 100 rpm and maintain the medium temperature at 37 ± 0.5℃. At 5 minutes, extract 5 mL of the dissolution solution and immediately replenish the isothermal medium. Filter the sample solution through a 0.45 μm microporous membrane. Take the filtrate and determine the adenosine content under the above chromatographic conditions. Calculate the cumulative dissolution percentage to evaluate the instantaneous release performance of the formulation.

[0072] 3. Moisture Absorption Weight Gain: The constant temperature and humidity weighing method was used. Appropriate amounts of tablets from each group were taken and accurately weighed to determine their initial mass (m1). These tablets were placed in a constant temperature and humidity chamber at a set temperature of 25℃ and a relative humidity (RH) of 75%. After 24 hours, the tablets were removed and accurately weighed again (m2). The percentage of moisture absorption weight gain was calculated using the formula (m2-m1) / m1×100% to evaluate the physical stability of the formulation under humid conditions.

[0073] 4. Powder Distribution Uniformity (RSD): After the premixing process in step (1), 10 samples (approximately 10 mg per sample) were randomly taken from different locations (top, middle, bottom, and edge) within the mixer. The content of the main component adenosine at each sampling point was determined using HPLC, and the relative standard deviation (RSD) of the 10 sets of data was calculated. The smaller this index, the more uniform the initial distribution of the ultrafine powder on the auxiliary material skeleton.

[0074] 5. Disintegration time: Refer to the disintegration time test method in General Chapter 0921 of the 2020 edition of the Chinese Pharmacopoeia. Take 6 tablets from each group and place them in a basket disintegrator. Use distilled water at 37±1℃ as the medium and record the time it takes for the tablets to completely disintegrate and pass through the sieve.

[0075] 6. Specific Surface Area (BET): Measured using a fully automated specific surface area and porosity analyzer. Appropriate amounts of each component tablet were taken and degassed (40℃, vacuum degassed for 6 hours) without damaging the overall structure. Nitrogen was used as the adsorbate, and the specific surface area was calculated according to the multi-point BET equation. This indicator is used to quantify the tightness of the bonding between the powder and the micropores of the excipients under pressure.

[0076] 7. Tablet Hardness and Friability: Hardness was tested using an automatic tablet hardness tester to measure radial breaking force. Ten tablets were tested in each group, and the average value was taken. Friability was measured according to General Chapter 0923 of the 2020 edition of the Chinese Pharmacopoeia. Approximately 6.5g of tablets were placed in a cylinder and run at 25 rpm for 100 cycles, and the percentage of mass loss was calculated.

[0077] 8. Microbial Limit Test: The test was conducted according to General Chapters 1105 and 1106 of the 2020 edition of the Chinese Pharmacopoeia, "Microbial Limit Test Method for Non-Sterile Products". Take 10g of each sample and add sterile sodium chloride-peptone buffer (pH 7.0) to 100mL. After homogenization, prepare a 1:10 test solution. Use the plate method to determine the total aerobic bacteria count, mold count, and yeast count, respectively. Results are expressed as colony forming units (CFU / g) to evaluate the sterilization effect of different processes and the microbial control level of the finished product.

[0078] The test results are shown in Table 1.

[0079] Table 1

[0080]

[0081] From the powder uniformity data in Table 1, the RSD value of Example 6 is 1.2%, while the RSD values ​​of Comparative Example 5 (mixing speed 10 rpm) and Comparative Example 6 (mixing speed 60 rpm) are 8.5% and 6.2%, respectively. This difference reflects the significant impact of premixing speed on the powder distribution. Within the speed range of 25-35 rpm, the composite motion field generated by the three-dimensional motion mixer can apply a moderate shear force to the material, allowing the fine-sized, high-surface-energy Cordyceps ultrafine powder to form a relatively stable physical adsorption state on the surface of microcrystalline cellulose PH102 particles and the edges of fiber micropores. When the speed is lower than the above range, the shear strength provided by the mixer is insufficient to effectively overcome the van der Waals forces and electrostatic forces between ultrafine powders, leading to local powder aggregation, which is reflected in an increased RSD value. When the speed is higher than the above range, the mechanical energy input is too high, which may cause the desorption of adsorbed powder or material segregation due to centrifugation, which is also not conducive to maintaining a uniform distribution.

[0082] The uniformity of the initial powder distribution is correlated with the effectiveness of subsequent ultra-high pressure treatment. Example 6 exhibited higher hardness (9.2 kg) and lower brittleness (0.21%) after high-pressure treatment, while Comparative Examples 5 and 6, whose rotational speed deviated from the optimal range, showed relatively weaker performance in the corresponding indicators. This phenomenon is because uniformly distributed powder can form a denser and more balanced physical bonding network under pressure, avoiding stress concentration caused by local aggregation or delamination, thus contributing to improved overall structural stability.

[0083] Ultra-high pressure (UHPP) treatment reshapes the microstructure of the formulation, which is a core factor in improving dissolution performance and disintegration characteristics. Comparing Example 6 with Comparative Example 3 (without UHPP treatment), a significant logical correlation can be observed between specific surface area, disintegration time, and dissolution rate. The specific surface area of ​​Example 6 (1.15...) () is far lower than comparative example 3 (3.52) The disintegration time (145s) was significantly shorter than that of Comparative Example 3 (285s), while the dissolution rate at 5 minutes (91.5%) was significantly improved. The data trends show a certain correlation between the decrease in specific surface area and the increase in dissolution rate.

[0084] Under ultra-high pressure conditions of 350-380 MPa, the ultrafine powders originally distributed on the particle surface may be displaced under pressure and enter the micropores of microcrystalline cellulose PH102. This process is accompanied by a reduction in the interparticle porosity and specific surface area. Simultaneously, due to the increased bonding tightness between the ultrafine powders and the excipient skeleton, in the initial stage of disintegration, the microcrystalline cellulose skeleton may promote the penetration rate of the dissolution medium through capillary effect. Combined with the micro-expansion effect of low-substituted hydroxypropyl cellulose, this leads to disintegration and release of the active ingredient in a shorter time. This explanation is consistent with the phenomenon in Example 6, which simultaneously exhibits a low specific surface area and a high dissolution rate.

[0085] The selection and proportioning of excipients exhibit a significant synergistic effect in improving the moisture-proof stability of formulations. In Comparative Example 4, after replacing microcrystalline cellulose PH102 with ordinary grade PH101, the moisture absorption weight gain increased from 1.8% in Example 6 to 4.9%, indicating that PH102-type microcrystalline cellulose has unique advantages in controlling the moisture absorption of formulations. PH102-type microcrystalline cellulose has specific particle size distribution and pore structure characteristics. Its larger particle size and specific porosity provide a more suitable physical carrying space for ultrafine powders, which is more conducive to the ultrafine powders being pressed into and fixed inside the pores during ultra-high pressure processing, thereby reducing the probability of contact between active ingredients and water molecules during storage. In Comparative Example 2, after adjusting the weight ratio of microcrystalline cellulose to maltodextrin to 0.5:1, the moisture absorption weight gain increased to 5.2%, and the dissolution rate decreased to 68.4%, indicating that the change in the excipient proportion has a significant impact on the overall performance of the formulation. This difference indicates that under ultra-high pressure, there is a suitable synergistic effect between microcrystalline cellulose PH102 and maltodextrin. When the PH102 ratio is relatively high (1.2-1.3:1), its fibrous skeleton structure can provide sufficient physical support space for the active ingredients. At the same time, maltodextrin fills the gaps between the fibers, forming a uniform physical shielding layer under pressure, effectively hindering the penetration path of water molecules into the formulation. However, when the maltodextrin ratio is too high, its own hygroscopic properties become the main factor increasing the hygroscopicity of the formulation. Furthermore, insufficient PH102 cannot form enough skeletal support, leading to changes in the medium permeation channel structure and a decrease in dissolution efficiency.

[0086] The protective effect of the process on heat-sensitive active ingredients was fully demonstrated in the comparative data. Comparative Example 1, using a traditional moist heat sterilization process, had an adenosine retention rate of only 62.4%, and due to the altered properties of the excipients caused by high temperature, the disintegration time was extended to 420 seconds, and the hardness decreased to 5.1 kg. In contrast, the ultra-high pressure treatment process (20-25℃) used in Examples 4-6 maintained a stable adenosine retention rate of over 96%. This indicates that ultra-high pressure treatment effectively avoids the risk of thermal degradation of heat-sensitive ingredients while achieving sterilization, and optimizes the microstructure of the formulation through the energy input of physical pressure, rather than destroying it.

[0087] Furthermore, the microbial limit test results further verified that the process of the present invention achieves sterilization function while optimizing physical properties. As shown in Table 1, the total microbial count of the Comparative Example 3 sample without any sterilization treatment was as high as 650 CFU / g, which does not meet the relevant hygiene standards. In contrast, the total microbial count of Comparative Example 1, which was sterilized by conventional 121℃ moist heat, and Examples 4-6, which were treated by the ultra-high pressure of the present invention at 350-380 MPa, was effectively controlled at a low level, achieving the same microbial control effect as high-temperature sterilization. This result confirms that the ultra-high pressure treatment process of the present invention can effectively sterilize microorganisms by destroying their cell structure through high hydrostatic pressure at room temperature (20-25℃), thereby completely avoiding the serious damage to heat-sensitive active ingredients (such as adenosine) in artificial Cordyceps sinensis caused by traditional moist heat sterilization processes (the adenosine retention rate of Comparative Example 1 was only 62.4%).

[0088] In summary, this invention, through the precise coupling of the specifications of artificial Cordyceps sinensis ultrafine powder, the specific ratio of excipients, and the "premix-ultra-high pressure" process parameters, achieves systematic optimization of various macroscopic performance indicators of the formulation while ensuring sterilization. Experimental data demonstrate that, under the combined effects of a premixing intensity of 25-35 rpm and pressure induction of 350-380 MPa, the formulation not only maintains an extremely high retention rate of active ingredients (≥96%) at room temperature, but also significantly improves mechanical strength (hardness ≥7.2 kg, friability ≤0.45%) while overcoming the common technical contradictions of high-density formulations, such as high hygroscopicity (hygroscopic weight gain ≤2.4%) and slow dissolution (dissolution rate ≥85.5% in 5 minutes). This comprehensive performance improvement is attributed to the physicochemical balance achieved between process parameters and material characteristics, providing a systematic solution for the industrial production of ultrafine powder formulations of precious traditional Chinese medicines that balances stability, activity, and efficient release.

Claims

1. A method for preparing a highly active compound health supplement containing Cordyceps militaris, Artemisia argyi, and Rhubarb, characterized in that, Includes the following steps: (1) Premixing: Artificial Cordyceps sinensis ultrafine powder, prepared Tangut rhubarb fine powder, Tibetan Artemisia argyi extract, microcrystalline cellulose PH102, maltodextrin, and low-substituted hydroxypropyl cellulose are put into a three-dimensional motion mixer and mixed at a speed that allows the ultrafine powder to be fully dispersed and adsorbed on the surface of the excipients. (2) Formulation: Add magnesium stearate and silicon dioxide to the mixture obtained in step (1), mix evenly, and then compress into tablets; (3) Ultra-high pressure treatment: After sealing the tablets, place them in an ultra-high pressure treatment chamber and treat them under pressure that can physically modify the tablet structure and improve its overall performance.

2. The preparation method according to claim 1, characterized in that, In step (1), the rotation speed is 25-35 rpm and the mixing time is 25-35 minutes.

3. The preparation method according to claim 1, characterized in that, In step (3), the pressure is 350-380 MPa, the temperature of the ultra-high pressure treatment is 20-25℃, and the constant pressure holding time is 50-70 minutes.

4. The preparation method according to claim 1, characterized in that, In step (3), the pressurization rate in the ultra-high pressure treatment chamber is 60 MPa / min, and the depressurization rate is 40 MPa / min.

5. The preparation method according to claim 1, characterized in that, The weight parts of each component in the preparation are as follows: 12-18 parts of artificial Cordyceps sinensis ultrafine powder, 2-4 parts of prepared Tangut rhubarb fine powder, 6-10 parts of Tibetan Artemisia argyi extract, 22-28 parts of microcrystalline cellulose PH102, 18-22 parts of maltodextrin, 6-10 parts of low-substituted hydroxypropyl cellulose, 1-2 parts of magnesium stearate, and 0.5-1.5 parts of silicon dioxide.

6. The preparation method according to claim 5, characterized in that, The weight ratio of microcrystalline cellulose PH102 to maltodextrin in the excipients is 1.2-1.3:

1.

7. The preparation method according to claim 1, characterized in that, The particle size of the artificial Cordyceps sinensis ultrafine powder in step (1) is 500-800 mesh, and it is prepared by the following method: after drying the artificial Cordyceps sinensis to a moisture content of ≤7%, it is subjected to deep cold air jet pulverization. During the pulverization process, the temperature of the pulverization chamber is maintained below -100℃, the pulverization pressure is set to 0.7-0.8 MPa, and the feeding speed is 5-10 kg / h.

8. The preparation method according to claim 1, characterized in that, The fine powder of Tangut rhubarb mentioned in step (1) is a 100-mesh fine powder prepared by wine stewing.

9. The preparation method according to claim 1, characterized in that, The Tibetan Artemisia leaf extract mentioned in step (1) is an extract powder obtained by reflux extraction with 75% ethanol and spray drying.

10. A highly active compound health care preparation of Cordyceps, Artemisia argyi, and Rhubarb, characterized in that, The formulation is prepared by the method described in any one of claims 1-9.

Images