Processing method of ganoderma lucidum spore powder used as pharmaceutic adjuvant

Abstract

The invention relates to the technical field of ganoderma lucidum spore powder processing, in particular to a ganoderma lucidum spore powder processing method for pharmaceutical excipients, which comprises the following steps: obtaining an original ganoderma lucidum spore powder raw material, and placing the original ganoderma lucidum spore powder raw material into a spiral conveying sterilization cabin; the method comprises the following steps: acquiring biological characteristic data of a raw material based on a preset spore activation target, and selecting a first biological enzyme preparation from a pre-established enzyme preparation library based on the data; the rotating speed of a screw rod of the spiral conveying sterilization cabin is controlled within the range of 5-25 rpm, and the temperature of a jacket is controlled within the range of 45-65 DEG C, so that the materials in the cabin reach and maintain a first preset process environment; in a first preset process environment, passing through a sectional type injection system integrated in a spiral conveying sterilization cabin; according to the method, the spore wall is mildly deconstructed by using the first bio-enzyme preparation, and the natural germination process of the spore wall is simulated, so that the damage of high temperature, high pressure and strong shearing force to active components is avoided, and the natural nutritional conformation and physiological activity of the ganoderma lucidum spores are furthest reserved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of ganoderma lucidum spore powder processing, and particularly relates to a ganoderma lucidum spore powder processing method for medicinal excipients. BACKGROUND

[0002] Ganoderma lucidum spores are reproductive cells of ganoderma lucidum, rich in polysaccharides, triterpenes, proteins and other bioactive substances, and are regarded as precious medicinal raw materials. However, the ganoderma lucidum spores have a very hard double-wall structure composed of chitin and glucan, which seriously hinders the digestion and absorption of the effective components in the human body. Therefore, the core of spore powder processing is how to effectively destroy or penetrate the spore wall.

[0003] At present, the existing processing technologies mainly include physical wall breaking method and solvent extraction method. The physical wall breaking method, such as high-speed airflow crushing or mechanical grinding, has high wall breaking rate, but the huge mechanical shearing force and instantaneous high temperature can easily damage the heat-sensitive active ingredients and cause spore oil oxidation and deterioration. In addition, the spore powder after wall breaking is more prone to moisture absorption and caking, which is not conducive to storage. The solvent extraction method can effectively dissolve part of the active substances, but usually has long process cycle, large solvent consumption, and may have residues. In addition, the spore powder after extraction often loses its physical form and part of the natural nutritional components as a functional food excipient.

[0004] Moreover, the existing technologies mainly focus on violent extraction or mechanical release of the contents of the spores, and completely ignore the physiological activity contained in the ganoderma lucidum spores as a life microcapsule. These methods cannot distinguish the live and dead states of the spores, and the processing process is static and passive, lacking the perception and response to the biological state of the material itself. SUMMARY

[0005] The present application provides a ganoderma lucidum spore powder processing method for medicinal excipients to solve the technical problems in the prior art.

[0006] The technical scheme for solving the above technical problems is as follows: a ganoderma lucidum spore powder processing method for medicinal excipients, comprising the following steps: S1, obtaining raw ganoderma lucidum spore powder raw materials, and placing them into a screw conveying sterilization cabin through a feeding device with metering function; S2, obtaining biological characteristic data of the raw materials based on a preset spore activation target, and selecting a first biological enzyme preparation from a pre-established enzyme preparation library based on the data; S3, controlling the screw rotation speed of the screw conveying sterilization cabin in the range of 5-25 rpm, and the jacket temperature in the range of 45℃-65℃, so that the materials in the cabin reach and maintain a first preset process environment; S4. In the first preset process environment, a segmented spraying system integrated in the screw conveying sterilization cabin is used to perform the first-stage precise spraying at a spraying pressure of 0.2-0.6 MPa, to introduce the atomized first biological enzyme preparation into the spore powder being conveyed, and the enzyme preparation is added in an amount of 0.5%-3.0% of the dry weight of the spore powder; S5. Based on the pressure data sequence output in real time by the plurality of pressure sensors arranged on the shell of the screw conveying sterilization cabin, a pressure distribution model in the cabin is constructed, and whether the spore population has entered the activation start state is determined based on the model; S6. After confirming that the spores have entered the activation start state, the second-stage spraying control instruction is generated based on the output of the pressure distribution model to adjust the second-stage spraying parameters of the segmented spraying system, and the second-stage spraying is performed at a spraying pressure of 0.3-0.8 MPa to introduce the second medium, drive and complete the deep activation process of the spore powder. S7. The multi-stage condensate water recovery device connected to the exhaust port of the screw conveying sterilization cabin is used to comprehensively recover and process the gas phase condensate generated in the activation process.

[0007] Preferably, the species of the original Ganoderma lucidum spore powder, the type of the cultivation substrate, and the storage time and humidity after harvesting are obtained, based on the species, the basic structure type of the spore shell chitin is determined, and based on the type of the cultivation substrate and the storage history data, the physiological aging degree of the spore shell is evaluated, the basic structure type of the spore shell chitin and the physiological aging degree are taken as input parameters, and the pre-established enzyme preparation library is matched, the pre-established enzyme preparation library contains a plurality of enzyme complexes for degradation of different chitin structures and high molecular polymers, based on the matching result, the optimal enzyme complex formula is output as the first biological enzyme preparation.

[0008] Preferably, based on the optimal action temperature range 50-60℃ of the selected first biological enzyme preparation, the target temperature interval 52-58℃ is determined as the core temperature parameter of the first preset process environment, the jacket heat conduction oil circulation system of the screw conveying sterilization cabin is started, the internal space of the cabin body is preheated at a temperature rising rate of 1-3℃ / min, based on the reaction time of the first biological enzyme preparation and the spores, and the material filling coefficient, the first rotation speed range of the screw of the screw conveying sterilization cabin is determined as 8-15 rpm, and the spore powder is run at the first rotation speed for 15-30 min in the preheated cabin body before the first-stage spraying is performed.

[0009] Preferably, the first biological enzyme preparation at least includes endochitinase, exochitinase and beta-glucanase with synergistic effect.

[0010] Preferably, several high-precision pressure sensors are installed at the feed end, middle section and discharge end of the screw conveyor sterilization chamber to acquire pressure data sequences, read the data of all pressure sensors in real time, and filter out instantaneous noise interference caused by mechanical vibration to obtain effective pressure trend data. Based on effective pressure trend data, the pressure levels of each area in the spiral conveyor sterilization chamber are identified and their changes over time are tracked. When the pressure level inside the chamber exceeds 0.05-0.15 MPa and this state is maintained for 3-8 minutes, it is determined that the spore population has synchronously entered the activation and start-up state.

[0011] Preferably, the second-stage injection parameters include the composition of the injection medium, the injection rate, the injection duration, and the activated injection area, switching the medium of the second-stage injection from an inert gas in standby state to a composite aqueous solution containing an energy substrate, mineral cofactors, and a cell membrane permeability enhancer. Based on the pressure distribution model, the number of regions with pressure exceeding the 0.05-0.15 MPa threshold is counted. Combined with the range of the pressure exceeding the threshold in these regions, the corresponding level is selected from the pre-set spray intensity levels. Based on the high-pressure core region identified by the pressure distribution model, a command is sent to the segmented spray system to start the nozzle and control the spray volume.

[0012] Preferably, the injection rate is in the range of 2-10 L / min and the injection duration is in the range of 5-15 min.

[0013] Preferably, the energy substrate is a complex composed of 2% to 5% trehalose and 1% to 3% low molecular weight active peptides in a ratio of 2:1 to 4:1. The mineral cofactor is a hydrated ion composed of 0.01%–0.05% zinc sulfate and 0.005%–0.02% manganese sulfate, and the cell membrane permeability enhancer is a mild surfactant of 0.05%–0.2%.

[0014] Preferably, the multi-stage condensate recovery device includes a primary cyclone separator with a processing air volume of 200-500 m3 / h, a secondary cryogenic coil condenser with a condensation temperature of 4-10℃, and a tertiary electrostatic precipitator with a voltage of 15-30 kV. The primary cyclone separator performs preliminary purification on the high-temperature and high-humidity gas discharged from the spiral conveyor sterilization chamber, allowing the pre-purified gas to enter the secondary cryogenic coil condenser. By precisely controlling the refrigerant temperature, efficient condensation of vapor phase moisture is achieved, and residual trace aerosols pass through the tertiary electrostatic precipitator. The collected primary condensate undergoes further processing, including: The primary condensate is pumped into an ultrafiltration membrane separation system to separate the concentrated components and the clear liquid; The concentrated components were introduced into a low-temperature vacuum concentration unit for further enrichment at a temperature of 35-4℃ and a vacuum degree of -0.08 to -0.095 MPa. The purified liquid is introduced into an integrated water treatment unit consisting of microporous filtration with a pore size of 0.1-0.5 μm and ultraviolet photocatalytic oxidation. The ultraviolet light has a wavelength of 254 nm and an intensity of 30-60 mW / cm².

[0015] Preferably, the process also includes post-maturation and stabilization treatment. The activated spore powder is discharged from the spiral conveyor sterilization chamber and immediately transported to a fluidized bed maturation chamber with ammonia filling and humidity control function. Based on the real-time online near-infrared spectral detection data of the spore powder, information on its moisture content and functional group changes is obtained. Based on the information on moisture content and functional group changes, the ammonia gas introduced into the maturation chamber is dynamically adjusted, and the temperature is controlled at 30-40℃, the relative humidity is controlled at 40%-60%, and the flow rate is controlled at 10-30 m / h. Under this environment, the spore powder undergoes a slow biochemical reaction and physical structure relaxation for 2-6 hours.

[0016] The beneficial effects of this invention are as follows: This invention uses a first biological enzyme preparation to gently deconstruct the spore wall, simulating its natural germination process. This method avoids the damage to active ingredients caused by high temperature, high pressure, and strong shear force, and preserves the natural nutritional conformation and physiological activity of Ganoderma lucidum spores to the greatest extent. This invention introduces a real-time feedback control system based on a pressure sensor. By monitoring the pressure changes caused by the trace amounts of endogenous gas released during the spore activation process, it can accurately determine whether the spore population has entered the activation start-up state, and dynamically trigger and adjust the spraying of the second stage nutrient medium accordingly. This greatly overcomes the quality fluctuations caused by batch differences in raw materials, and ensures that the final product has batch-to-batch consistency and process reproducibility. Attached Figure Description

[0017] Figure 1 This is a flowchart of the present invention. Detailed Implementation

[0018] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0019] In the description of this application, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the stated features. In the description of this application, "multiple" means two or more, unless otherwise explicitly specified.

[0020] In the description of this application, the term "for example" is used to mean "used as an example, illustration, or description." Any embodiment described as "for example" in this application is not necessarily to be construed as being more preferred or advantageous than other embodiments. The following description is provided to enable any person skilled in the art to make and use the invention. Details are set forth in the following description for purposes of explanation. It should be understood that those skilled in the art will recognize that the invention can be made without using these specific details. In other instances, well-known structures and processes will not be described in detail to avoid obscuring the description of the invention with unnecessary detail. Therefore, the invention is not intended to be limited to the embodiments shown, but is consistent with the broadest scope of the principles and features disclosed in this application.

[0021] like Figure 1 This embodiment provides a method for processing Ganoderma lucidum spore powder for pharmaceutical excipients, comprising the following steps: S1. Obtain the raw material of Ganoderma lucidum spore powder and place it into the spiral conveyor sterilization chamber through a feeding device with metering function; S2. Based on the preset spore activation target, obtain the biological characteristic data of the raw material, and select the first biological enzyme preparation from the pre-established enzyme preparation library based on the data; S3. Control the screw speed of the screw conveyor sterilization chamber within the range of 5-25 rpm and the jacket temperature within the range of 45℃-65℃ to ensure that the material inside the chamber reaches and maintains the first preset process environment. S4. Under the first preset process environment, the first stage of precise spraying is performed by the segmented spraying system integrated in the spiral conveyor sterilization chamber at a spraying pressure of 0.2-0.6MPa, introducing the atomized first biological enzyme preparation into the spore powder being transported. The amount of enzyme preparation added is 0.5% to 3.0% of the dry weight of the spore powder. It should be noted that the atomized first biological enzyme preparation achieves its penetration into the surface and gaps of the spore powder particles through the systemic interaction of atomization characteristics and material flow. The atomized enzyme preparation has the characteristics of large specific surface area and slow settling velocity. When it comes into contact with the spore powder in the screw conveyor, it can be mixed in two ways: one is gravity settling + airflow diffusion, where the droplets diffuse to the surface of the material layer with the slight airflow in the chamber during the slow settling process, covering the surface spore powder; the other is material agitation contact, where the relative motion between the material particles occurs when the screw rotates and propels the material forward. After the surface material comes into contact with the droplets, the agitation action carries the enzyme preparation into the interior of the material.

[0022] S5. Based on the real-time pressure data sequence output by multiple pressure sensors installed on the shell of the spiral conveyor sterilization chamber, construct a pressure distribution model inside the chamber, and determine whether the spore population has entered the activation and start-up state based on the model. S6. Once it is confirmed that the spores have entered the activation and start-up state, a second-stage spray control command is immediately generated based on the output of the pressure distribution model to adjust the second-stage spray parameters of the segmented spray system and execute the second-stage spray at a spray pressure of 0.3-0.8MPa to introduce the second medium, drive and complete the deep activation process of the spore powder. S7. A multi-stage condensate recovery device connected to the exhaust port of the spiral conveyor sterilization chamber is used to fully recover and treat the gaseous condensates generated during the activation process.

[0023] Furthermore, the species, cultivation substrate type, post-harvest storage time, and storage environment humidity of the original Ganoderma lucidum spore powder were obtained. Based on the species, the basic structure type of chitin in the spore shell was determined. Based on the cultivation substrate type and storage history data, the physiological aging degree of the spore shell was assessed. The basic structure type and physiological aging degree of the spore shell chitin were used as input parameters and matched with a pre-established enzyme preparation library. The pre-established enzyme preparation library contains a variety of enzyme complexes that target the degradation of different chitin structures and polymers. Based on the matching results, the optimal enzyme complex formulation was output as the first biological enzyme preparation.

[0024] Furthermore, based on the optimal operating temperature range of the selected first biological enzyme preparation (50℃-60℃), the target temperature range of 52℃-58℃ was determined as the core temperature parameter of the first preset process environment. The jacketed heat transfer oil circulation system of the screw conveyor sterilization chamber was started to preheat the internal space of the chamber at a heating rate of 1℃-3℃ / min. Based on the reaction time between the first biological enzyme preparation and the spores, as well as the material filling coefficient, the first rotational speed range of the screw of the screw conveyor sterilization chamber was determined to be 8-15 rpm. Before the first stage of spraying, the spore powder was allowed to run in the preheated chamber at the first rotational speed for 15-30 minutes.

[0025] Furthermore, the first biological enzyme preparation includes at least endochitinase, exochitinase and β-glucanase with synergistic effects, and the proportions of each component are finely adjusted according to the physiological aging degree of the spore shell.

[0026] It should be noted that 40% to 60% of the endochondrinase breaks the β-(1→4) glycosidic bonds inside chitin, decomposing long-chain chitin into short-chain oligosaccharides and forming a large number of enzymatic sites on the spore shell. This component accounts for the highest proportion because its function is a prerequisite for the subsequent exonuclease to function. Especially for chitin with high degree of polymerization, a higher proportion of endonuclease is needed to break the shell structure. 20%–35% of exochitinase: hydrolyzes from the non-reducing end of the chitin chain, further breaking down short-chain oligosaccharides into N-acetylglucosamine monosaccharides, expanding the fissures and pores of the spore shell. The proportion of this component is lower than that of endonuclease because it depends on the short-chain substrate produced by endonuclease, while avoiding substrate competition caused by excessive exonuclease. 15%–30% β-glucanase: Degrades β-glucan components in the spore shell. β-glucan is the encapsulating matrix of chitin. After degradation, more chitin targets can be exposed, improving the efficiency of endo- and exo-chitinases.

[0027] It should be noted that the proportions of each component are finely adjusted according to the physiological aging degree of the sporocapsid to adapt to the structural differences in the sporocapsid caused by aging. When the sporocapsid structure is intact and the chitin chains are long when the aging is mild, it is necessary to enhance the shell-breaking ability of the endonuclease, increase the proportion of endonuclease by 2% to 5%, such as from 50% to 55%, decrease the proportion of exonuclease by 1% to 3%, such as from 25% to 22%, and keep the proportion of β-glucanase unchanged to ensure that the endonuclease preferentially breaks long-chain chitin. When the sporopod is moderately aged, there are certain microcracks and partial degradation of chitin chains. It is necessary to balance the effects of endonuclease and exonuclease. The ratio of endonuclease is slightly adjusted by ±1%, and the ratio of exonuclease is increased by 2% to 4%. Exonuclease is used to efficiently decompose short-chain chitin. At the same time, the ratio of β-glucanase is increased by 1% to 2% to further expose chitin targets. When spores are severely aged, the spore shell has many pores and the chitin chains are short. It is necessary to enhance the complete degradation ability of exonucleases, increase the proportion of exonuclease by 3% to 5%, decrease the proportion of endonuclease by 2% to 4%, and keep the proportion of β-glucanase unchanged to avoid enzyme waste caused by excessive endonuclease.

[0028] Furthermore, several high-precision pressure sensors are installed at the feed end, middle section and discharge end of the screw conveyor sterilization chamber to acquire pressure data sequences, read the data of all pressure sensors in real time, and filter out instantaneous noise interference caused by mechanical vibration to obtain effective pressure trend data. Based on effective pressure trend data, the pressure levels of each area in the spiral conveyor sterilization chamber are identified and their changes over time are tracked. When the pressure level inside the chamber exceeds 0.05-0.15 MPa and this state is maintained for 3-8 minutes, it is determined that the spore population has synchronously entered the activation and start-up state.

[0029] Furthermore, the second-stage injection parameters include the composition of the injection medium, the injection rate, the injection duration, and the activated injection area, switching the medium of the second-stage injection from the inert gas in the standby state to a composite aqueous solution containing energy substrate, mineral cofactors, and cell membrane permeability enhancers. Based on the pressure distribution model, the number of regions with pressure exceeding the 0.05-0.15 MPa threshold is counted. Combined with the range of the pressure exceeding the threshold in these regions, the corresponding level is selected from the pre-set spray intensity levels. Based on the high-pressure core region identified by the pressure distribution model, a command is sent to the segmented spray system to start the nozzle and control the spray volume.

[0030] It should be noted that the pressure distribution model provides three types of information for parameter adjustment, including the location of the high-pressure core area, the distribution of the pressure change rate, and the overall pressure level. The high-pressure core area is the cluster of grid cells with the highest pressure identified by the model. This area is the hot spot area where spore activation is most active and the second medium should be sprayed first. The pressure change rate distribution is the pressure change rate of each grid cell output by the model. Areas with low change rate indicate that the activation process is slow and the injection volume needs to be increased to enhance the reaction. Areas with high change rate indicate that the activation is sufficient and the basic injection volume can be maintained. Overall pressure level: If the average pressure inside the chamber is close to the upper limit of the first dynamic pressure threshold, it indicates that the activation has entered the middle stage and the injection intensity of the second medium needs to be controlled to avoid excessive gas production and abnormal pressure rise. Spraying medium switching: The process switches from the first biological enzyme preparation in the first stage to the second stage. The spraying medium in the second stage contains a complex aqueous solution of energy substrate, mineral cofactors, and cell membrane permeability enhancers. This switching is based on the needs of the activation stage. When the enzyme preparation in the first stage has started shell degradation, the second stage needs to provide reaction energy, activate enzyme activity, and promote the release of contents through the second medium to complete deep activation. Injection pressure setting: This pressure is higher than the first stage because the second stage requires a stronger atomization effect to penetrate into the spore shell, while ensuring that the medium can cover the deep material in the high-pressure core area. Injection rate and area adjustment: For the high-pressure core area, the nozzles at the corresponding positions are instructed to start first. For areas with low pressure change rate, the nozzles are instructed to increase the injection volume to accelerate activation through local enrichment of the second medium. The components of the second medium drive deep activation through synergistic effects: The energy substrate provides the raw materials for ATP synthesis in the enzymatic hydrolysis reaction, enhances the catalytic activity of chitinase, and accelerates the degradation of the spore shell; Mineral cofactors, as enzyme activators, can stabilize the spatial structure of enzymes and prevent enzyme activity from decreasing due to prolonged reaction time. Cell membrane permeability enhancers can disrupt the phospholipid bilayer structure of spore cell membranes, increase membrane permeability, promote the release of enzymatic hydrolysis products, and accelerate the entry of the second medium into the spore, forming a degradation-release-re-degradation cycle, and driving activation to a deeper level.

[0031] Furthermore, the injection rate is in the range of 2-10 L / min and the injection duration is in the range of 5-15 min.

[0032] Furthermore, the energy substrate is a complex composed of 2%–5% trehalose and 1%–3% low molecular weight active peptides in a ratio of 2:1–4:1. The mineral cofactor is a hydrated ion composed of 0.01%–0.05% zinc sulfate and 0.005%–0.02% manganese sulfate, and the cell membrane permeability enhancer is a mild surfactant of 0.05%–0.2%.

[0033] Furthermore, the multi-stage condensate recovery device includes a first-stage cyclone separator with a processing air volume of 200-500 m3 / h, a second-stage cryogenic coil condenser with a condensation temperature of 4-10℃, and a third-stage electrostatic precipitator with a voltage of 15-30 kV. The first-stage cyclone separator performs preliminary purification on the high-temperature and high-humidity gas discharged from the spiral conveyor sterilization chamber, allowing the pre-purified gas to enter the second-stage cryogenic coil condenser. By precisely controlling the refrigerant temperature, efficient condensation of vapor phase moisture is achieved, and residual trace aerosols pass through the third-stage electrostatic precipitator. The collected primary condensate undergoes further processing, including: The primary condensate is pumped into an ultrafiltration membrane separation system to separate the concentrated components and the clear liquid; The concentrated components were introduced into a low-temperature vacuum concentration unit for further enrichment at a temperature of 35-4℃ and a vacuum degree of -0.08 to -0.095 MPa. The purified liquid is introduced into an integrated water treatment unit consisting of microporous filtration with a pore size of 0.1-0.5 μm and ultraviolet photocatalytic oxidation. The ultraviolet light has a wavelength of 254 nm and an intensity of 30-60 mW / cm².

[0034] Furthermore, the process includes post-maturation and stabilization treatments. The activated spore powder is discharged from the spiral conveyor sterilization chamber and immediately transported to a fluidized bed maturation chamber with ammonia filling and humidity control. Based on real-time online near-infrared spectral data of the spore powder, information on its moisture content and functional group changes is obtained. Based on the information on moisture content and functional group changes, the ammonia gas introduced into the maturation chamber is dynamically adjusted, and the temperature is controlled at 30-40℃, the relative humidity is controlled at 40%-60%, and the flow rate is controlled at 10-30 m³ / h. Under this environment, the spore powder undergoes a slow biochemical reaction and physical structure relaxation for 2-6 hours.

[0035] It should be noted that the optimal temperature range for the slow biochemical reaction of spore powder post-maturation is 30-40℃. When the temperature is below 30℃, the catalytic activity of residual enzymes is insufficient, and the biochemical reaction cycle needs to be extended to more than 8 hours, reducing production efficiency. When the temperature is above 40℃, the triterpenoid components of Ganoderma lucidum will undergo thermal degradation, and the polysaccharide molecular chains are easily broken, affecting product quality. If the real-time detection shows that the moisture content is >18%, it indicates that the moisture evaporation rate is insufficient. The ammonia temperature needs to be increased by 1-2℃ to accelerate the evaporation of moisture on the material surface by increasing the ambient temperature, so that the moisture content drops back to the range of 12% to 18%. If the strength of C=O bonds in the functional groups is increased, it indicates that the local temperature may be too high. The ammonia temperature needs to be reduced by 2-3℃. At the same time, check whether the fluidized bed air distribution plate is blocked to ensure temperature uniformity. If the moisture content and functional groups are normal, maintain the temperature at the median value of 35℃.

[0036] A nitrogen relative humidity of 40%–60% can maintain the environmental equilibrium threshold for the moisture content of spore powder. When the nitrogen relative humidity is <40%, it will accelerate the loss of moisture from the material, leading to a decrease in moisture content. When the relative humidity is >60%, the material will absorb moisture from ammonia, leading to an increase in moisture content. If the moisture content of the material is detected to be <12%, the relative humidity of ammonia needs to be increased by 5%–10% by using a humidifier to increase the water vapor content in ammonia, allowing the material to absorb moisture through fluidized contact. If the moisture content is >18%, the relative humidity needs to be decreased by 5%–10% by using a dehumidifier to reduce the water vapor content in ammonia, accelerating the evaporation of moisture from the material. If the moisture content is between 14% and 16%, the relative humidity should be maintained at 50%.

[0037] The biochemical reactions in the post-ripening stage mainly involve subsequent degradation catalyzed by residual enzymes and moderate conversion of active ingredients, specifically including: Subsequent degradation of residual chitinase: After deep activation, microcracks have appeared in the spore shell. The temperature of 30-40℃ and the moisture content of the material in the chamber can maintain the catalytic ability of the residual chitinase, continue to degrade the remaining chitin in the spore shell, and reduce hard shell impurities in subsequent products. Moderate polymerization of polysaccharides: Small molecule polysaccharides in spore powder undergo moderate polymerization under mild temperature and moisture conditions, which can enhance the bioactivity of polysaccharides. Oxidation inhibition reaction: The low-oxygen environment inside the chamber can inhibit the oxidation reaction of active ingredients. At the same time, the trace inert components in ammonia can further stabilize the spatial structure of enzymes, prevent enzymes from being inactivated by oxidation, and ensure that biochemical reactions proceed continuously and gently.

[0038] Example 1 Embodiment 1 of the present invention provides a method for processing Ganoderma lucidum spore powder for pharmaceutical excipients, comprising the following steps: S1. Based on the chitin structure and moderate aging degree of the spore powder, the enzyme complex formulation is selected as 50% endochitinase, 28% exochitinase and 22% β-glucanase. S2. Set the screw speed to 12 rpm and the jacket temperature to 55℃; S3. Set the spray pressure to 0.4 MPa and the enzyme addition amount to 1.8% of the dry weight of the spore powder; S4. When the pressure continues to exceed the threshold of 0.10MPa for 5 minutes, the second stage of injection is triggered. The injection intensity level is 2, the injection rate is 5L / min, and the duration is 10min. S5. The spore powder underwent a slow biochemical reaction and physical structural relaxation for 4 hours.

[0039] Example 2 Embodiment 2 of the present invention provides a method for processing Ganoderma lucidum spore powder for pharmaceutical excipients, comprising the following steps: S1. For denser spore walls and higher aging levels, an enhanced enzyme formulation is used, consisting of 55% endochitinase, 30% exochitinase, and 15% β-glucanase. S2. Reduce the screw speed to 10 rpm to prolong the reaction time, and set the jacket temperature to 58℃; S3. Set the spray pressure to 0.5 MPa and the enzyme addition amount to 2.5% of the dry weight of the spore powder; S4. When the pressure continues to exceed the threshold of 0.12 MPa for 6 minutes, the second stage of injection is triggered, with an injection intensity level of 4, an injection rate of 8 L / min, and a duration of 12 min. S5. The spore powder was subjected to a slow biochemical reaction and physical structural relaxation for 5 hours.

[0040] Example 3 Example 3 of the present invention provides a method for processing Ganoderma lucidum spore powder for pharmaceutical excipients, comprising the following steps: S1. For higher aging levels, the enzyme formula uses 58% endogenous chitinase, 25% exogenous chitinase and 17% β-glucanase. S2. Adjust the screw speed to 8 rpm to ensure full reaction, and set the jacket temperature to 56℃; S3. Set the spray pressure to 0.45 MPa and the enzyme addition amount to 3.0% of the dry weight of the spore powder; S4. When the pressure continues to exceed the threshold of 0.08 for 7 minutes, the second stage of injection is triggered, with an injection intensity level of 1, an injection rate of 3L / min, and a duration of 8 minutes. S5. The spore powder underwent a slow biochemical reaction and physical structural relaxation for 6 hours.

[0041] Example 4 Example 4 of this invention provides a method for processing Ganoderma lucidum spore powder for pharmaceutical excipients, comprising the following steps: S1. For fresh, structurally intact spore walls, a mild enzyme formula is selected, consisting of 45% endochitinase, 22% exochitinase, and 33% β-glucanase. S2. Adjust the screw speed to 15 rpm and set the jacket temperature to 52℃; S3. Set the spray pressure to 0.3 MPa and the enzyme addition amount to 0.8% of the dry weight of the spore powder; S4. When the pressure continues to exceed the threshold of 0.09 for 3.5 minutes, the second stage of injection is triggered, with an injection intensity level of 3, an injection rate of 6L / min, and a duration of 9 minutes. S5. The spore powder was subjected to a slow biochemical reaction and physical structural relaxation for 2 hours.

[0042] Based on Examples 1-4, the following table can be derived: Table 1 Properties Example 1 Example 2 Example 3 Example 4 Enzyme formulation (endo / exo / beta-glucanase) 50 / 28 / 22 55 / 30 / 15 58 / 25 / 17 45 / 22 / 33 Enzyme addition 1.8% 2.5% 3.0% 0.8 Core temperature 55℃ 58℃ 56℃ 52℃ Screw speed 12 rpm 10 rpm 8 rpm 15 rpm Pressure trigger time 5 6 7 3.5 Second stage injection level 2 4 1 3 Curing time 4h 5h 6h 2h As shown in Table 1: This invention can precisely adapt to raw materials of different species and storage conditions by adjusting enzyme formulation, dosage, temperature and rotation speed, and achieve different product goals. The differentiated combination of parameters in each embodiment proves that the processing method has the ability to adapt to different raw material conditions.

[0043] It should be noted that the descriptions of each embodiment in the above embodiments have different focuses. For parts that are not described in detail in a certain embodiment, please refer to the relevant descriptions in other embodiments.

[0044] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0045] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A method for processing Ganoderma lucidum spore powder for use as a pharmaceutical excipient, characterized in that, Includes the following steps: S1. Obtain the raw material of Ganoderma lucidum spore powder and place it into the spiral conveyor sterilization chamber through a feeding device with metering function; S2. Based on the preset spore activation target, obtain the biological characteristic data of the raw material, and select the first biological enzyme preparation from the pre-established enzyme preparation library based on the data; S3. Control the screw speed of the screw conveyor sterilization chamber within the range of 5-25 rpm and the jacket temperature within the range of 45℃-65℃ to ensure that the material inside the chamber reaches and maintains the first preset process environment. S4. Under the first preset process environment, the first stage of precise spraying is performed by the segmented spraying system integrated in the spiral conveyor sterilization chamber at a spraying pressure of 0.2-0.6MPa, introducing the atomized first biological enzyme preparation into the spore powder being transported. The amount of enzyme preparation added is 0.5% to 3.0% of the dry weight of the spore powder. S5. Based on the real-time pressure data sequence output by multiple pressure sensors installed on the shell of the spiral conveyor sterilization chamber, construct a pressure distribution model inside the chamber, and determine whether the spore population has entered the activation and start-up state based on the model. S6. Once it is confirmed that the spores have entered the activation and start-up state, a second-stage spray control command is immediately generated based on the output of the pressure distribution model to adjust the second-stage spray parameters of the segmented spray system and execute the second-stage spray at a spray pressure of 0.3-0.8MPa to introduce the second medium, drive and complete the deep activation process of the spore powder. S7. A multi-stage condensate recovery device connected to the exhaust port of the spiral conveyor sterilization chamber is used to fully recover and treat the gaseous condensates generated during the activation process.

2. The method for processing Ganoderma lucidum spore powder for pharmaceutical excipients according to claim 1, characterized in that, In step S2, the species, cultivation substrate type, post-harvest storage time, and storage environment humidity of the original Ganoderma lucidum spore powder are obtained. Based on the species, the basic structure type of chitin in the spore shell is determined. Based on the cultivation substrate type and storage history data, the physiological aging degree of the spore shell is assessed. The basic structure type of chitin in the spore shell and the physiological aging degree are used as input parameters and matched with a pre-established enzyme preparation library. The pre-established enzyme preparation library contains a variety of enzyme complexes that target the degradation of different chitin structures and polymers. Based on the matching results, the optimal enzyme complex formulation is output as the first biological enzyme preparation.

3. The method for processing Ganoderma lucidum spore powder for pharmaceutical excipients according to claim 1, characterized in that, In step S3, based on the optimal operating temperature range of the selected first biological enzyme preparation (50℃-60℃), the target temperature range (52℃-58℃) is determined as the core temperature parameter of the first preset process environment. The jacketed heat transfer oil circulation system of the screw conveyor sterilization chamber is started to preheat the internal space of the chamber at a heating rate of 1℃-3℃ / min. Based on the reaction time between the first biological enzyme preparation and the spores, and the material filling coefficient, the first rotation speed range of the screw of the screw conveyor sterilization chamber is determined to be 8-15 rpm. Before the first stage of spraying is executed, the spore powder runs in the preheated chamber at the first rotation speed for 15-30 minutes.

4. The method for processing Ganoderma lucidum spore powder for pharmaceutical excipients according to claim 1, characterized in that, In S4, the first biological enzyme preparation includes at least an endogenous chitinase, an exogenous chitinase, and a β-glucanase that have synergistic effects.

5. A method for processing Ganoderma lucidum spore powder for pharmaceutical excipients according to claim 1, characterized in that, In step S5, several high-precision pressure sensors are installed at the feed end, middle section and discharge end of the spiral conveyor sterilization chamber to acquire pressure data sequences, read the data of all pressure sensors in real time, and filter out instantaneous noise interference caused by mechanical vibration to obtain effective pressure trend data. Based on effective pressure trend data, the pressure levels of each area in the spiral conveyor sterilization chamber are identified and their changes over time are tracked. When the pressure level inside the chamber exceeds 0.05-0.15 MPa and this state is maintained for 3-8 minutes, it is determined that the spore population has synchronously entered the activation and start-up state.

6. A method for processing Ganoderma lucidum spore powder for pharmaceutical excipients according to claim 1, characterized in that, In S6, the second-stage injection parameters include the composition of the injection medium, the injection rate, the injection duration, and the activated injection area. The medium of the second-stage injection is switched from the inert gas in the standby state to a composite aqueous solution containing energy substrate, mineral cofactors, and cell membrane permeability enhancers. Based on the pressure distribution model, the number of regions with pressure exceeding the 0.05-0.15 MPa threshold is counted. Combined with the range of the pressure exceeding the threshold in these regions, the corresponding level is selected from the pre-set spray intensity levels. Based on the high-pressure core region identified by the pressure distribution model, a command is sent to the segmented spray system to start the nozzle and control the spray volume.

7. A method for processing Ganoderma lucidum spore powder for pharmaceutical excipients according to claim 6, characterized in that, The injection rate is in the range of 2-10 L / min and the injection duration is in the range of 5-15 min.

8. A method for processing Ganoderma lucidum spore powder for pharmaceutical excipients according to claim 6, characterized in that, The energy substrate is a complex composed of 2%–5% trehalose and 1%–3% low molecular weight active peptides in a ratio of 2:1–4:

1. The mineral cofactor is a hydrated ion composed of 0.01%–0.05% zinc sulfate and 0.005%–0.02% manganese sulfate, and the cell membrane permeability enhancer is a mild surfactant of 0.05%–0.2%.

9. A method for processing Ganoderma lucidum spore powder for pharmaceutical excipients according to claim 1, characterized in that, In S7, the multi-stage condensate recovery device includes a first-stage cyclone separator with a processing air volume of 200-500 m3 / h, a second-stage cryogenic coil condenser with a condensation temperature of 4-10℃, and a third-stage electrostatic precipitator with a voltage of 15-30 kV. The first-stage cyclone separator performs preliminary purification on the high-temperature and high-humidity gas discharged from the spiral conveyor sterilization chamber, allowing the pre-purified gas to enter the second-stage cryogenic coil condenser. By precisely controlling the refrigerant temperature, efficient condensation of vapor phase moisture is achieved, and residual trace aerosols pass through the third-stage electrostatic precipitator. The collected primary condensate undergoes further processing, including: The primary condensate is pumped into an ultrafiltration membrane separation system to separate the concentrated components and the clear liquid; The concentrated components were introduced into a low-temperature vacuum concentration unit for further enrichment at a temperature of 35-4℃ and a vacuum degree of -0.08 to -0.095 MPa. The purified liquid is introduced into an integrated water treatment unit consisting of microporous filtration with a pore size of 0.1-0.5 μm and ultraviolet photocatalytic oxidation. The ultraviolet light has a wavelength of 254 nm and an intensity of 30-60 mW / cm².

10. A method for processing Ganoderma lucidum spore powder for pharmaceutical excipients according to claim 1, characterized in that, It also includes post-maturation and stabilization treatment. The activated spore powder is discharged from the spiral conveyor sterilization chamber and immediately transported to the fluidized bed maturation chamber with ammonia filling and humidity control function. Based on the real-time online near-infrared spectral detection data of the spore powder, the information on its water content and functional group changes is obtained. Based on the information on water content and functional group changes, the ammonia gas introduced into the maturation chamber is dynamically adjusted, and the temperature is controlled at 30-40℃, the relative humidity is controlled at 40% to 60%, and the flow rate is controlled at 10-30 m / h. Under this environment, the spore powder undergoes a slow biochemical reaction and physical structure relaxation for 2 to 6 hours.

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