Micro-ecological regulation medicine preparation and split charging integrated system for diabetics

Abstract

The invention relates to the technical field of pharmaceutical preparations, in particular to a micro-ecological regulation drug preparation and split charging integrated system for diabetics. The system comprises an adjusting medicine raw material preparation unit, an adjusting medicine fermentation unit, an adjusting medicine processing and preparing unit and an automatic medicine subpackaging unit, and experimental ingredient analysis can be carried out by selecting probiotic strains, prebiotic components prepared in advance and short-chain fatty acid so as to generate the ingredient proportion of the micro-ecological adjusting medicine; the preparation method comprises the following steps: mixing the components according to the proportion of the micro-ecological regulation drug, feeding the mixture into a fermentation tank for microbial growth fermentation, dynamically controlling fermentation conditions, and simultaneously performing low-temperature freeze-drying treatment and drug concentration and microencapsulation preparation to obtain micro-ecological regulation microencapsulated drug components; and obtaining micro-ecological regulation drug requirements and carrying out automatic control sub-packaging treatment and modified atmosphere packaging treatment to generate the micro-ecological regulation modified atmosphere packaging drug. According to the invention, the activity of the medicine can be kept in the preparation and subpackage processes.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and particularly to an integrated system for the preparation and packaging of a microecological regulating drug for diabetic patients. Background Art

[0002] The occurrence of diabetes is closely related to insufficient insulin secretion or insulin resistance. The long-term hyperglycemic state can cause damage to multiple systems such as blood vessels, nerves, and kidneys. In recent years, more and more studies have shown that the occurrence and development of diabetes are closely related to the imbalance of the intestinal microecology. The disorder of the intestinal microecology affects pancreatic islet function, metabolic status, and immune response through various channels, thereby exacerbating the pathological process of diabetes. At present, the microecological regulating products for diabetic patients on the market mainly include probiotics, prebiotics, and their combined preparations. These products regulate the structure and function of the intestinal flora and improve the intestinal microecological environment, thus helping to control blood sugar levels. However, there are certain deficiencies in the production, preparation, and packaging processes of existing microecological regulating products. For example, the control of environmental factors such as temperature, pH, and dissolved oxygen is insufficient, and it is difficult to achieve automated and integrated packaging. It is often difficult to effectively maintain their activity, resulting in a significant reduction in drug efficacy, thereby affecting production efficiency and product quality. Summary of the Invention

[0003] Based on this, it is necessary for the present invention to provide an integrated system for the preparation and packaging of a microecological regulating drug for diabetic patients to solve at least one of the above technical problems.

[0004] To achieve the above object, an integrated system for the preparation and packaging of a microecological regulating drug for diabetic patients includes the following units:

[0005] A regulating drug raw material preparation unit for selecting clinically verified probiotic strains, including lactic acid bacteria and bifidobacteria, and conducting experimental ingredient analysis on the probiotic strains, pre-prepared prebiotic components, and short-chain fatty acids to generate the ingredient ratio of the microecological regulating drug; after mixing the probiotic strains, prebiotic components, and short-chain fatty acids according to the ingredient ratio of the microecological regulating drug by using an automated batching system, generating a to-be-fermented regulating drug mixture and feeding it into a fermentation tank;

[0006] A regulating drug fermentation unit for performing microbial growth fermentation on the to-be-fermented regulating drug mixture by using the fermentation tank, and dynamically controlling the corresponding fermentation conditions of temperature, pH, and dissolved oxygen during the fermentation process in a segmented manner through a programmable logic controller to obtain the fermented active ingredient of the microecological regulating drug;

[0007] A regulating drug preparation unit is used to perform low-temperature freeze-drying treatment on the fermentation active ingredients of the microecological regulating drug to obtain the freeze-dried drug ingredients of the microecological regulation; perform drug concentration and microencapsulation preparation on the freeze-dried drug ingredients of the microecological regulation to obtain the microencapsulated drug ingredients of the microecological regulation.

[0008] A drug automatic packaging unit is used to obtain the microecological regulating drug requirements corresponding to different specifications, and based on the microecological regulating drug requirements corresponding to different specifications, use cold chain technology to perform automatic control packaging treatment on the microencapsulated drug ingredients of the microecological regulation to obtain the dispensed dose drugs of the microecological regulation; perform modified atmosphere packaging treatment on the dispensed dose drugs of the microecological regulation to generate the modified atmosphere packaged drugs of the microecological regulation.

[0009] Furthermore, the regulating drug raw material preparation unit includes the following functions:

[0010] By selecting clinically verified probiotic strains, including lactic acid bacteria and bifidobacteria, and performing selection screening and dissolution on the probiotic strains to obtain the probiotic strain seed liquid;

[0011] Based on the pre-prepared prebiotic components and short-chain fatty acids, perform strain interaction effect analysis on the corresponding probiotic strains, where the prebiotic components include dietary fiber and oligosaccharides, and the short-chain fatty acids include acetic acid, propionic acid, and butyric acid, to generate a different prebiotic and short-chain fatty acid combination - strain interaction effect map;

[0012] Based on the different prebiotic and short-chain fatty acid combination - strain interaction effect map, perform experimental ingredient analysis on the probiotic strain seed liquid, prebiotic components, and short-chain fatty acids to generate an experimental table of the active ingredients of the microbial regulating drug;

[0013] According to the experimental table of the active ingredients of the microbial regulating drug, screen out the ingredient ratio combination corresponding to the best microecological regulating effect to generate the ingredient ratio of the microecological regulating drug;

[0014] According to the ingredient ratio of the microecological regulating drug, use an automatic ingredient system to mix the probiotic strain seed liquid, prebiotic components, and short-chain fatty acids to generate a mixed liquid of the drug to be fermented and regulated, and send it to the fermentation tank.

[0015] Furthermore, the specific ingredient ratio of the microecological regulating drug is that both lactic acid bacteria and bifidobacteria are 1×106CFU / mL, dietary fiber is 0.4%, oligosaccharides is 0.3%, acetic acid is 0.1%, and butyric acid is 0.05%.

[0016] Furthermore, the regulating drug fermentation unit includes the following functions:

[0017] Obtain the chemical components corresponding to each active component and the microbial metabolic pathway from the drug mixture to be fermented and adjusted, and determine the proportion of nutrient components such as carbon source, nitrogen source, and trace elements corresponding to the drug mixture to be fermented and adjusted during the fermentation process based on the chemical components and microbial metabolic pathway corresponding to each active component, so as to generate the proportion of nutrient components for microbial metabolic fermentation;

[0018] Use a fermenter to perform microbial growth fermentation treatment on the drug mixture to be fermented and adjusted according to the proportion of nutrient components for microbial metabolic fermentation, so as to record and generate the metabolic fermentation process of the microecological regulating drug;

[0019] Obtain the microbial biomass growth rate and metabolite concentration corresponding to the fermentation process from the metabolic fermentation process of the microecological regulating drug, and perform microbial metabolic growth analysis on the metabolic fermentation process of the microecological regulating drug based on the microbial biomass growth rate and metabolite concentration, so as to generate the metabolic growth curve of the microecological regulating drug;

[0020] Divide different fermentation culture stages through the metabolic growth curve of the microecological regulating drug, and perform cumulative analysis of the active ingredient of the drug on the metabolic fermentation process of the microecological regulating drug based on different fermentation culture stages, so as to generate the cumulative amount of metabolite of the active ingredient of the microecological regulating drug corresponding to different fermentation stages;

[0021] Based on the cumulative amount of metabolite of the active ingredient of the microecological regulating drug corresponding to different fermentation stages, segmentally and dynamically control the fermentation conditions such as temperature, pH, and dissolved oxygen corresponding to each fermentation stage during the fermentation process through a programmable logic controller, so as to obtain the active ingredient of the fermented microecological regulating drug.

[0022] Further, the proportion of nutrient components for microbial metabolic fermentation corresponding to the culture component ratio in the fermenter is specifically that the carbon source accounts for 2%-5% of the total fermenter, the nitrogen source accounts for 0.5%-1% of the total fermenter, and the trace element is 5-100 μg / L.

[0023] Further, the regulating drug processing and preparation unit includes the following functions:

[0024] Use a directional cooling device to control the cooling rate not exceeding 2°C per minute to perform preliminary heat temperature cooling treatment on the active ingredient of the fermented microecological regulating drug to obtain a pre-microecological regulating drug mixture with temperature;

[0025] Use a segmented low-temperature pre-freezing technology to control the freezing temperature between -30°C and -50°C to perform step-by-step low-temperature freezing treatment on the pre-microecological regulating drug mixture with temperature to obtain a microecological regulating low-temperature frozen drug component;

[0026] Perform vacuum drying optimization treatment on the microecological regulating low-temperature frozen drug component to obtain a microecological regulating freeze-dried drug component;

[0027] The microecological regulation freeze-dried drug components are subjected to drug concentration treatment to obtain highly concentrated microecological regulation drug components;

[0028] The highly concentrated microecological regulation drug components are subjected to microencapsulation preparation to obtain microencapsulated microecological regulation drug components.

[0029] Furthermore, the vacuum drying optimization treatment for the cryogenically frozen microecological regulation drug components includes:

[0030] Obtain the solubility corresponding to each drug active ingredient in the cryogenically frozen microecological regulation drug components;

[0031] By introducing a trace amount of inert gas during the vacuum drying process corresponding to the cryogenically frozen microecological regulation drug components to guide the direction of the molecular flow of the drug components, and using the dry solubility loss calculation formula based on the solubility corresponding to each drug active ingredient to quantitatively calculate the loss of the vacuum drying process corresponding to the cryogenically frozen microecological regulation drug components, so as to obtain the dry solubility loss of the drug active ingredients;

[0032] Based on the dry solubility loss of the drug active ingredients, the vacuum drying process corresponding to the cryogenically frozen microecological regulation drug components is optimized by vacuum drying, and the contact ratio between the flow rate of the inert gas and the cryogenically frozen microecological regulation drug components is precisely controlled to obtain the freeze-dried microecological regulation drug components.

[0033] Furthermore, the dry solubility loss calculation formula is specifically:

[0034]

[0035] In the formula, ΔL(t) is the dry solubility loss of the drug active ingredient at time t, T is the total duration of the drying process, n is the total number of drug active ingredients, i is the item index of the drug active ingredient, S i (t) is the solubility corresponding to the i-th drug active ingredient at time t, is the initial solubility of the i-th drug active ingredient before drying, C i (t) is the drug component concentration corresponding to the i-th drug active ingredient at time t, α i is the concentration solubility loss influence coefficient corresponding to the i-th drug active ingredient, P(t) is the vacuum pressure of the drying environment at time t, W(t) is the temperature of the drying environment at time t, H(t) is the humidity of the drying environment at time t, and η is the correction coefficient of the dry solubility loss of the drug active ingredient.

[0036] Furthermore, the microencapsulation preparation of the highly concentrated microecological regulation drug components includes:

[0037] Obtain plant encapsulating excipients, and perform microencapsulation compatibility pretreatment on the highly concentrated drug components for microecological regulation based on the plant encapsulating excipients to obtain a stable matrix mixed component for the microecological regulation drug;

[0038] Use poly(lactic-co-glycolic acid) to perform microencapsulation on the stable matrix mixed component for the microecological regulation drug to generate a preliminary particle component of the microencapsulated drug for microecological regulation;

[0039] Perform supercritical fluid drying on the preliminary particle component of the microencapsulated drug for microecological regulation to obtain the microencapsulated drug component for microecological regulation.

[0040] Furthermore, the drug automatic packaging unit includes the following functions:

[0041] Obtain the microecological regulation drug requirements corresponding to different specifications;

[0042] Determine the drug specification dispensing dose for the microencapsulated drug component for microecological regulation based on the microecological regulation drug requirements corresponding to different specifications to generate the microecological regulation drug dispensing doses corresponding to different specifications;

[0043] Perform automatic control dispensing on the microencapsulated drug component for microecological regulation using cold chain technology based on the microecological regulation drug dispensing doses corresponding to different specifications to obtain the microecological regulation dispensed dose drug;

[0044] Perform modified atmosphere packaging on the microecological regulation dispensed dose drug by using temperature-controlled packaging materials and adjusting the inert gas components in the package to generate the microecological regulation modified atmosphere packaged drug.

[0045] The beneficial effects of the present invention:

[0046] The integrated system for the preparation and packaging of microecological regulatory drugs for diabetic patients proposed by the present invention is generally composed of a raw material preparation unit for regulatory drugs, a fermentation unit for regulatory drugs, a processing and preparation unit for regulatory drugs, and an automatic drug packaging unit. Compared with the prior art, the beneficial effects of this application are as follows: By selecting probiotic strains verified through clinical trials, the effectiveness and safety of the selected strains in terms of health are ensured. Lactobacilli and Bifidobacteria are common types of probiotics that have been widely studied and proven to be able to effectively regulate the intestinal microbial community and promote intestinal health. By strictly screening and dissolving these strains, a reliable source of bacterial strains for the subsequent preparation process is provided. Additionally, through experimental ingredient analysis of probiotic strains, pre-prepared prebiotic components, and short-chain fatty acids, the proportion combination of ingredients with the most significant microecological regulatory effect is screened out. This step is crucial in the optimization process of the entire probiotic formula and relies on a large amount of experimental data support in the early stage. By precisely adjusting the proportions of probiotics, prebiotics, and short-chain fatty acids, the functions of probiotics can be maximally activated, and the balance of the intestinal microecology can be promoted. For example, certain probiotics exhibit stronger proliferation ability and metabolic activity in the presence of specific prebiotics and short-chain fatty acids, thus more effectively improving intestinal health. This proportion combination of ingredients will provide a solid theoretical basis and technical guarantee for the commercial production of the product. At the same time, by using an automatic batching system, according to the finally determined proportion of ingredients for the microecological regulatory drug, probiotic strains, prebiotics, and short-chain fatty acids are precisely mixed to generate a mixed solution of the regulatory drug to be fermented. The use of the automatic system can ensure the efficiency and accuracy of the batching process, avoid errors in manual operations, and improve the stability of production, and can maximally ensure the ingredient consistency of each batch of products, ensuring that probiotics can exert their best efficacy during the fermentation process, thereby generating a fermentation product with a microecological regulatory effect. Secondly, by using a fermentation tank to perform microbial growth fermentation treatment on the drug mixed solution according to the proportion of nutritional components metabolized by microorganisms, and using a programmable logic controller to segmentally and dynamically control the corresponding fermentation conditions such as temperature, pH, and dissolved oxygen during the fermentation process, an ideal growth environment can be provided for microorganisms, thus ensuring that microorganisms can metabolize under the best conditions and generate the ideal drug product. During this process, key fermentation parameters such as temperature, pH value, and dissolved oxygen can be finely controlled, enabling microorganisms to continuously grow in the fermentation tank and ensuring that the synthesis of their metabolites reaches the expected level. Regularly record and monitor the metabolism of the microecological regulatory drug during the fermentation process, thereby improving the controllability and stability of the production process. This control mechanism helps to improve the production efficiency, stability, and quality of the microecological regulatory drug and can be flexibly adjusted according to actual production requirements, thereby improving resource utilization rate.Then, by subjecting the fermented active ingredients of the microecological regulatory drug to low-temperature freeze-drying treatment, the damage caused by water freezing during the freezing process of the drug ingredients can be effectively reduced. The key to this step lies in slowly reducing the temperature to ensure the stability of the cell structure and active ingredients in the drug, avoiding the formation of ice crystals caused by rapid freezing, so that the drug can maintain a longer shelf life during subsequent processing. By concentrating the microecological regulatory freeze-dried drug ingredients to remove excess solvents or moisture, the concentration of the drug ingredients can be effectively increased, thereby enhancing the efficacy of the drug. This can significantly increase the concentration of the active ingredients of the drug. Also, through microencapsulation preparation, the active ingredients in the microecological regulatory drug are encapsulated in microcapsules, which can effectively protect the microorganisms or active ingredients in the drug from the influence of the external environment, such as oxidation, light, or temperature changes, etc., thereby extending the shelf life of the drug and improving its usage effect, avoiding the rapid decomposition of the drug ingredients in the body, reducing the side effects of the drug, and making the action of the drug in the body more precise and lasting, thus enhancing the overall effect of the microecological regulatory drug. Finally, by obtaining the microecological regulatory drug requirements corresponding to different specifications, the physiological states and disease type requirements of different patient groups vary greatly, so the dosage form, specification, dosage, etc. of the drug need to be precisely planned. Through this process, the demand for drugs of different specifications can be accurately identified, providing basic data support for subsequent production, sub-packaging, distribution, etc. Also, by using cold chain technology to perform automated control sub-packaging on the microecological regulatory microencapsulated drug ingredients based on the microecological regulatory drug requirements corresponding to different specifications, the quality and stability of the microencapsulated drug during production and transportation can be ensured. It is prone to decomposition or failure in environments with high temperature, excessive or too little humidity, which helps to ensure the quality of the drug throughout the production, packaging, transportation, and storage links, and can maintain the ideal storage temperature of the microencapsulated drug, thus ensuring the stable release of the drug efficacy. In addition, by using temperature-controlled packaging materials and adjusting the inert gas components in the package to perform modified atmosphere packaging on the microecological regulatory sub-packaged dosage drugs, the stability and shelf life of the microecological regulatory drugs can be further improved. The modified atmosphere packaging technology can significantly reduce the occurrence of oxidation reactions and delay the degradation process of the drug by adjusting the gas components in the package, especially the ratio of oxygen, carbon dioxide, and nitrogen. It can further reduce the impact of temperature changes on the drug, thus ensuring the quality and production efficiency of the drug during transportation and storage. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Other features, objects, and advantages of the present invention will become more apparent by reading the detailed description of the non-limiting embodiments with reference to the following drawings:

[0048] Figure 1 It is a unit schematic diagram of the integrated system for the preparation and sub-packaging of the microecological regulatory drug for diabetic patients according to the present invention;

[0049] Figure 2 is Figure 1 a schematic diagram of the functional process of the preparation unit for the regulatory drug raw materials in

[0050] Figure 3 is Figure 1 a schematic diagram of the functional process of the fermentation unit for the regulatory drug in

[0051] Figure 4 a schematic diagram of the experimental table of the microbial regulatory drug active ingredients of the present invention;

[0052] Figure 5 a schematic diagram of the microecological regulatory drug metabolic growth curve of the present invention. Specific embodiments

[0053] The following clearly and completely describes the technical system of the present invention with reference to the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative efforts belong to the scope of protection of the present invention.

[0054] To achieve the above object, please refer to Figures 1 to 5 , the present invention provides an integrated system for the preparation and packaging of a microecological regulatory drug for diabetic patients, and the system includes the following units:

[0055] A preparation unit for the regulatory drug raw materials, which is used to select clinically verified probiotic strains, including lactic acid bacteria and bifidobacteria, and conduct experimental ingredient analysis on the probiotic strains, pre-prepared prebiotic components, and short-chain fatty acids to generate the ingredient ratio of the microecological regulatory drug; after mixing the probiotic strains, prebiotic components, and short-chain fatty acids according to the ingredient ratio of the microecological regulatory drug by using an automated batching system, a mixed solution of the regulatory drug to be fermented is generated and sent to a fermentation tank;

[0056] A fermentation unit for the regulatory drug, which is used to carry out microbial growth fermentation on the mixed solution of the regulatory drug to be fermented by using a fermentation tank, and dynamically control the corresponding temperature, pH, and dissolved oxygen fermentation conditions during the fermentation process in a segmented manner by using a programmable logic controller to obtain the active ingredients of the microecological regulatory drug fermentation;

[0057] A processing and preparation unit for the regulatory drug, which is used to carry out low-temperature freeze-drying treatment on the active ingredients of the microecological regulatory drug fermentation to obtain the freeze-dried drug components of the microecological regulation; carry out drug concentration and microencapsulation preparation on the freeze-dried drug components of the microecological regulation to obtain the microencapsulated drug components of the microecological regulation;

[0058] The automated drug filling unit is used to obtain the demand for microecological regulating drugs corresponding to different specifications, and based on the demand for microecological regulating drugs corresponding to different specifications, use cold chain technology to automatically control the filling and processing of microecological regulating microencapsulated drug ingredients to obtain microecological regulating filled dose drugs; and perform modified atmosphere packaging processing on the microecological regulating filled dose drugs to generate microecological regulating modified atmosphere packaging drugs.

[0059] In the embodiment of the present invention, please refer to Figure 1 As shown, it is a schematic diagram of the units of the integrated system for preparing and packaging microecological regulation drugs for diabetic patients of the present invention. In this example, the integrated system for preparing and packaging microecological regulation drugs for diabetic patients includes the following units:

[0060] S1: The drug regulating raw material preparation unit is used to select clinically verified probiotic strains, including lactic acid bacteria and bifidobacteria, and conduct experimental batching analysis on the probiotic strains and the pre-prepared prebiotic components and short-chain fatty acids to generate the proportion of microecological regulating drug ingredients; the probiotic strains, prebiotic components and short-chain fatty acids are mixed according to the proportion of microecological regulating drug ingredients using an automated batching system to generate a fermented regulating drug mixture, which is then sent to the fermentation tank;

[0061] In the embodiments of the present invention, by selecting probiotic strains that have been clinically verified and have good health benefits, these strains mainly include lactic acid bacteria (such as Lactobacillus acidophilus, Lactobacillus bulgaricus) and bifidobacteria (such as Bifidobacterium bifidum, Bifidobacterium breve). These strains need to pass strict clinical verification, and the interaction effects of the strains are analyzed by combining pre-prepared prebiotic components and short-chain fatty acids, aiming to study the effects of these components on the growth and activity of the strains. The prebiotic components include dietary fibers (such as dextran, fructooligosaccharide) and oligosaccharides (such as galactooligosaccharide, xylooligosaccharide). These components can promote the proliferation of probiotics and regulate the balance of intestinal microbiota. The short-chain fatty acids include acetic acid, propionic acid, and butyric acid, which have the effects of regulating the intestinal pH value and inhibiting the growth of pathogenic microorganisms. In the experiment, in vitro culture is used to mix the above-mentioned prebiotics and short-chain fatty acids with probiotic strains, set different concentration gradients and observe the growth of the strains, and use gas chromatography (GC) to detect the production amount of short-chain fatty acids. The activity of the strains is evaluated by the agar plate method, and its growth curve, colony number, and metabolites are analyzed. Systematic analysis is also carried out by experimental design methods (such as orthogonal experimental design method) to evaluate the effects of different ingredient combinations. By mixing various prebiotics (such as oligosaccharides and dietary fibers) and short-chain fatty acids (acetic acid, propionic acid, butyric acid) with probiotic strains in different proportions, a series of experiments are carried out to determine the growth status of the strains, the production amount of short-chain fatty acids, and their potential for regulating the intestinal microecology of diabetic patients. An automated liquid handling system is used to accurately proportion each component to ensure the accuracy of the formula for each experimental group, so as to select the ratio with the best microecological regulation effect and obtain the best combination. Further, the specific ratio combination is that both lactic acid bacteria and bifidobacteria are 1×106 CFU / mL, dietary fiber is 0.4%, oligosaccharide is 0.3%, acetic acid is 0.1%, and butyric acid is 0.05%, so as to generate the corresponding proportion of the microecological regulation drug ingredients. Then, according to the best proportion of the microecological regulation drug ingredients, an automated batching system is used to prepare the drug. The batching system consists of multiple high-precision automated liquid handling units and can achieve precise mixing of probiotic strains, prebiotic components, and short-chain fatty acids. During the operation, first, according to the determined ratio, the automated system extracts the corresponding components from the pre-prepared prebiotic raw material and short-chain fatty acid storage tanks and pumps them to the mixing tank. The probiotic strains are transported to the mixing system through a vacuum extraction system. In the mixing tank, various components will be mixed by high-speed stirring to ensure their uniform distribution. During this process, the temperature, pH value, and other environmental conditions will be strictly controlled to maintain the activity of the probiotics. After mixing, a mixed liquid of the drug to be fermented and regulated is generated and sent into the fermentation tank for corresponding fermentation.

[0062] S2: Adjust the drug fermentation unit, which is used to carry out microbial growth fermentation on the fermentation-adjusting drug mixture to be fermented in a fermentation tank, and segmentally and dynamically control the corresponding temperature, pH, and dissolved oxygen fermentation conditions during the fermentation process through a programmable logic controller to obtain the active ingredients of the microecological regulatory drug fermentation;

[0063] In the embodiments of the present invention, the regulatory drug mixture to be fermented is analyzed by high performance liquid chromatography (HPLC) or gas chromatography-mass spectrometry (GC-MS) to qualitatively and quantitatively determine the chemical components of each active component in the mixture, and these components include polysaccharides, amino acids, lipids, etc. By analyzing the molecular structure and chemical properties of each active component, the corresponding microbial metabolic pathways are further deduced, and the proportions of carbon sources (such as glucose, sucrose), nitrogen sources (such as ammonium salts, urea) and trace elements (such as zinc, copper, iron, etc.) required during the fermentation process are calculated to optimize the nutrient components of the mixture. Through mathematical models and calculation formulas, the proportion of fermentation nutrient components suitable for microbial metabolism is generated, specifically, the carbon source accounts for 2%-5% of the total fermenter, the nitrogen source accounts for 0.5%-1% of the total fermenter, and the trace elements are 5-100 μg / L.After preparing the fermentation-adjusted drug mixture and its corresponding nutrients according to the previously calculated proportion of fermentation nutrients using a fermenter, fermentation treatment is carried out. The fermenter should be a device with monitoring functions such as temperature, pH, and dissolved oxygen, and be adjusted according to the designed fermentation conditions (such as the temperature set at 37°C and the pH set at 6.5). During the fermentation process, parameters such as the temperature, pH value, and dissolved oxygen concentration in the fermenter are monitored in real time and dynamically adjusted according to the preset conditions. Fermentation broth samples are collected regularly through an automatic sampling device to analyze the growth status of microorganisms and the changes in metabolites. During the fermentation process, the microbial biomass at each time point is recorded (for example, through turbidity measurement or cell counting method), as well as the production amount of drug regulatory components (such as polysaccharides and bioactive peptides). Based on these data, a mathematical model is used to fit the growth curve of microorganisms. Usually, common microbial growth models (such as the Monod model, Logistic model, etc.) are used for analysis. According to the growth rate of microbial biomass and the changes in metabolite concentration, the metabolic growth curve of the microecological regulatory drug is plotted, and the fermentation process is divided into multiple different stages, such as the growth lag phase, logarithmic growth phase, stationary phase, etc. Within each stage, the growth rate of microorganisms, metabolic activities, and the accumulation amount of active ingredients are different. In the growth lag phase, microorganisms mainly absorb exogenous carbon and nitrogen sources for cell proliferation, and the active ingredients of the drug are less at this time. When entering the logarithmic growth phase, the growth rate of microorganisms is the fastest, and the production amount of metabolites increases significantly. The stationary phase is when the accumulation of metabolites reaches a peak and begins to stabilize gradually. On this basis, by analyzing the changes in metabolite concentration in each stage, the accumulation amount of drug active ingredients in each stage is evaluated, and a programmable logic controller (PLC) is used to perform dynamic segmented control on the key fermentation conditions (such as temperature, pH, dissolved oxygen) of the fermenter. In the lag phase, the temperature is reduced, the pH value is controlled, and the dissolved oxygen level is reduced to promote the adaptive growth of microorganisms. In the logarithmic growth phase, the temperature is appropriately increased, the pH and dissolved oxygen concentration are adjusted to accelerate the proliferation of microorganisms and the accumulation of metabolites. When entering the stationary phase, a constant temperature and pH value are maintained, and the supply of dissolved oxygen is optimized to ensure the maximum accumulation of active ingredients. The PLC system will achieve precise dynamic adjustment according to the preset fermentation process control parameters to ensure that the best growth and metabolic conditions are reached in each fermentation stage, and finally obtain the fermentation active ingredients of the microecological regulatory drug.

[0064] S3: The regulatory drug processing and preparation unit is used to perform low-temperature freeze-drying treatment on the fermentation active ingredients of the microecological regulatory drug to obtain freeze-dried microecological regulatory drug ingredients; perform drug concentration and microencapsulation preparation on the freeze-dried microecological regulatory drug ingredients to obtain microencapsulated microecological regulatory drug ingredients.

[0065] In the embodiments of the present invention, by using a directional cooling device to control the cooling rate of the microecological regulatory drug fermentation active ingredient, it is ensured that the cooling process does not exceed 2°C per minute. Specifically, a cooling device with an adjustable cooling rate is adopted during implementation, such as a laminar flow cooling tower or a cooling water tank with a precise temperature control system. A temperature sensor is provided in the cooling device to monitor the temperature change of the drug mixture components in real time to ensure the stability of the cooling process. After the drug fermentation liquid or solution enters the cooling area, the control system automatically adjusts the flow rate of the cooling medium (such as cooling water or coolant), and the drug mixture components are gradually cryogenically frozen by adopting a segmented low-temperature pre-freezing technology. The temperature of the drug mixture components is segmented by a cryogenic freezing device to ensure that the freezing temperature remains between -30°C and -50°C. The freezing device used is a freezing tunnel or a freezer, which is provided with multiple temperature control areas and can accurately adjust the freezing temperature of each stage. In the initial pre-cooling stage, the temperature of the drug mixture components gradually decreases to about -30°C, enters a transition stage with a slower freezing rate, and the drug mixture components are frozen to -50°C. During this process, a temperature monitoring system is used to monitor the freezing environment in real time to ensure that the temperature control error does not exceed ±1°C. At the same time, drying treatment is carried out in a vacuum environment to remove the moisture in the drug and maintain the microecological active ingredients of the drug, thereby obtaining the microecological regulatory freeze-dried drug components. The microecological regulatory freeze-dried drug components that have been dried previously are also concentrated by using a membrane separation technology or an evaporation concentration device. During specific operation, the microecological regulatory freeze-dried drug components are dissolved and then sent into a multi-stage membrane filtration device (such as an ultrafiltration membrane or a reverse osmosis membrane). This device can remove the moisture and soluble small-molecule substances in the solution through step-by-step filtration, thereby concentrating the drug components. The drug components will be concentrated to the required concentration under certain temperature and pressure conditions. Then, the concentrated drug components are encapsulated in a suitable carrier material (such as polymers, liposomes, etc.) by using a solvent evaporation method or a spray drying method. During specific implementation, the concentrated drug components and the carrier material are mixed in a certain proportion to form a uniform solution or emulsion, and the solution is sprayed into the drying air stream through a high-pressure sprayer. The solvent evaporates quickly, and the drug components are encapsulated in tiny particles to form microencapsulated drugs. During the microencapsulation process, the operating temperature needs to be strictly controlled between 30 - 50°C to avoid loss of drug components caused by excessive temperature. This microencapsulation process ensures that the drug components can be slowly released or targeted released through the protection of the carrier material. The microencapsulated drug components can be subjected to subsequent packaging and sub-packaging processes to finally obtain the microecological regulatory microencapsulated drug components.

[0066] S4: The automated drug dispensing unit is used to obtain the requirements of microecological regulatory drugs corresponding to different specifications, and based on the requirements of microecological regulatory drugs corresponding to different specifications, use cold chain technology to perform automated control and dispensing on the microecological regulatory microencapsulated drug components to obtain microecological regulatory dispensed dose drugs; perform modified atmosphere packaging on the microecological regulatory dispensed dose drugs to generate microecological regulatory modified atmosphere packaged drugs.

[0067] In the embodiments of the present invention, by analyzing in detail the demand for microecological regulation drugs in diabetic patients, the determination of the demand is based on the patient's physique, disease stage, drug concentration requirements, etc., and in combination with the drug prescription requirements of clinical medicine, the demand for drugs of different specifications is determined. Combining the pharmacological effects and dosing regimens of the drugs, the required drug specifications (such as the dose taken each time, the dosing frequency per week, etc.) are further determined. At this time, the determined specifications include low doses (such as 500 mg), medium doses (such as 1000 mg), and high doses (such as 2000 mg), so as to obtain the demand for microecological regulation drugs corresponding to different specifications. By determining the specification dispensing dose of the previously prepared microencapsulated drug components for microecological regulation according to the previously obtained drug demand, a precise weighing device is used to measure each microencapsulated drug component, and an automated dispensing device is used to achieve the dispensing of drugs of different specifications. For example, for patients who need a 1000 mg dose, the drug will be dispensed into each drug package containing 1000 mg of microencapsulated components according to the quality standard of the microencapsulated components. Through the linkage of multiple automated devices, the precise dispensing of drugs of different specifications (500 mg, 1000 mg, 2000 mg, etc.) is achieved. After the dispensing is completed, a cold chain technology is adopted for the processed drugs after dispensing. The cold chain technology is to ensure the stability of the microecological regulation drugs after dispensing and prevent the drug components, especially the microencapsulated probiotics, from becoming ineffective or degrading due to temperature rise. In specific operations, through the cold chain logistics method, and using a temperature-controlled dispensing room or automated dispensing equipment for drug dispensing, the temperature in the cold chain dispensing equipment is strictly controlled between 2°C and 8°C to ensure that the activity of the microencapsulated drug components is not affected by the external environment, thus obtaining the microecological regulation dispensed dose drugs. Then, the microecological regulation drugs that have been dispensed are subjected to modified atmosphere packaging treatment. The modified atmosphere packaging technology can effectively prevent the drug components from being affected by moisture, oxidation, or deterioration during storage and transportation. During specific implementation, first, a temperature-controlled packaging material suitable for the microecological regulation drugs is selected. Usually, a high-performance film material with good air permeability and isolation is selected. These materials can prevent the influence of the external environment on the drugs while controlling the temperature. The packaging machine dispenses the drugs into pre-set packaging bags, and then a specific proportion of inert gases such as nitrogen and carbon dioxide is filled into the interior of the packaging bags through an inert gas mixing system, and the active ingredients of the microecological regulation drugs are maintained. During the packaging process, by strictly controlling the time of gas filling and the proportion of gas components, it is ensured that each bag of drugs can be stored in the best environment, and finally, the microecological regulation modified atmosphere packaging drugs are generated.

[0068] Furthermore, the regulatory drug raw material preparation unit includes the following functions:

[0069] By selecting clinically verified probiotic strains, including lactic acid bacteria and bifidobacteria, and screening and dissolving the probiotic strains to obtain a probiotic strain seed solution;

[0070] Based on the pre-prepared prebiotic components and short-chain fatty acids, the strain interaction effect analysis of the corresponding probiotic strains is performed, wherein the prebiotic components include dietary fiber and oligosaccharides, and the short-chain fatty acids include acetic acid, propionic acid and butyric acid, so as to generate different prebiotic and short-chain fatty acid combination-strain interaction effect maps;

[0071] Based on the different prebiotic and short-chain fatty acid combination-strain interaction effect maps, the experimental ingredients of probiotic strain seed liquid, prebiotic components and short-chain fatty acids were analyzed to generate an experimental table of active ingredients of microbial regulation drugs;

[0072] Preferably, the combination of ingredient ratios corresponding to the most microecological regulation effect is screened out according to the experimental table of active ingredients of microbial regulation drugs to generate the ingredient ratios of microecological regulation drugs;

[0073] According to the proportion of microecological regulating drug ingredients, the probiotic strain seed liquid, prebiotic components and short-chain fatty acids are mixed using an automated batching system to generate a fermented regulating drug mixture, which is then sent to a fermentation tank.

[0074] As an embodiment of the present invention, refer to Figure 2 As shown, Figure 1 The functional flow chart of the drug raw material preparation unit is shown in FIG. 1 . In this embodiment, the drug raw material preparation unit includes the following functions:

[0075] S11: by selecting clinically verified probiotic strains, including lactic acid bacteria and bifidobacteria, and selecting, screening and dissolving the probiotic strains to obtain a probiotic strain seed liquid;

[0076] In an embodiment of the present invention, by selecting probiotic strains that have been clinically verified and have good health benefits, these strains mainly include lactic acid bacteria (such as Lactobacillus acidophilus, Lactobacillus bulgaricus) and bifidobacteria (such as Bifidobacterium bifidum, Bifidobacterium breve), these strains need to pass strict clinical verification to ensure that they have high viability and health benefits. In actual operation, the strains are cultured separately in the culture medium and their growth curves are detected to select suitable strains. At the same time, the morphological characteristics of the strains are observed under a microscope, and the metabolic characteristics of the strains are confirmed by biochemical tests. After the strains are screened, they are dissolved, and the dissolution step uses physiological saline or an appropriate buffer. The temperature and pH value are controlled according to the characteristics of the strains to ensure that the activity of the strains is fully retained, and the strain seed liquid is prepared. The seed liquid needs to be sterile to avoid contamination by exogenous microorganisms, and the colony forming unit (CFU) of the seed liquid is measured using a spectrophotometer to ensure that the number of bacteria is within the specified range, and finally the probiotic strain seed liquid is obtained.

[0077] S12: Analyze the strain interaction effects on the corresponding probiotic strains based on the pre-prepared prebiotic components and short-chain fatty acids, where the prebiotic components include dietary fiber and oligosaccharides, and the short-chain fatty acids include acetic acid, propionic acid, and butyric acid, to generate a map of the interaction effects of different prebiotics and short-chain fatty acid combinations - strains;

[0078] In the embodiments of the present invention, by combining the pre-prepared prebiotic components and short-chain fatty acids to analyze the strain interaction effects, the purpose is to study the effects of these components on the growth and activity of the strains. The prebiotic components include dietary fiber (such as dextran, fructooligosaccharide) and oligosaccharides (such as galactooligosaccharide, xylooligosaccharide), and these components can promote the proliferation of probiotics and regulate the balance of intestinal microorganisms. The short-chain fatty acids include acetic acid, propionic acid, and butyric acid, which have the effects of regulating the intestinal pH value and inhibiting the growth of pathogenic microorganisms. In the experiment, in vitro culture is used to mix the above-mentioned prebiotics and short-chain fatty acids with the probiotic seed solution, set different concentration gradients, observe the growth of the strains, and use gas chromatography (GC) to detect the production amount of short-chain fatty acids, and evaluate the activity of the strains by the agar plate method, analyze their growth curves, colony numbers, and metabolites, to generate the corresponding interaction effect map. The map shows the effects of different combinations on each probiotic strain, including the promoting or inhibiting effects, and finally generates a map of the interaction effects of different prebiotics and short-chain fatty acid combinations - strains.

[0079] S13: Analyze the experimental ingredients of the probiotic strain seed solution, prebiotic components, and short-chain fatty acids based on the map of the interaction effects of different prebiotics and short-chain fatty acid combinations - strains to generate an experimental table of the active ingredients of the microbial regulatory drug;

[0080] In the embodiments of the present invention, further ingredient analysis of the probiotic seed solution, prebiotic components, and short-chain fatty acids is carried out by combining the aforementioned interaction effect map. At this time, systematic analysis is carried out by the experimental design method (such as the orthogonal experimental design method) to evaluate the effects of different ingredient combinations. By mixing various prebiotics (such as oligosaccharides and dietary fiber) and short-chain fatty acids (acetic acid, propionic acid, butyric acid) with the probiotic seed solution in different proportions, a series of experiments are carried out to measure the growth status of the strains, the production amount of short-chain fatty acids, and their potential for regulating the intestinal microecology of diabetic patients. During the specific operation, an automated liquid handling system is used to accurately proportion each component to ensure the accuracy of the formula for each experimental group. During the experiment, high-performance liquid chromatography (HPLC) is used to analyze the content of prebiotics, and the production amount of short-chain fatty acids during the fermentation process is monitored, and finally an experimental table of the active ingredients of the microbial regulatory drug (as Figure 4 shown) is generated.

[0081] S14: Screen out the ingredient ratio combination corresponding to the best microecological regulation effect according to the experimental table of microbial regulation of drug active ingredients, so as to generate the ingredient ratio of the microecological regulation drug.

[0082] In the embodiment of the present invention, according to the effects of different ingredient combinations in the experimental table of microbial regulation of drug active ingredients determined previously, the best ratio scheme corresponding to the probiotic strain seed liquid, prebiotic components and short-chain fatty acids is screened out. By comprehensively analyzing the data, the ratio with the best microecological regulation effect is selected to obtain the best combination. Further, the specific ratio combination is that both lactic acid bacteria and bifidobacteria are 1×106 CFU / mL, dietary fiber is 0.4%, oligosaccharide is 0.3%, acetic acid is 0.1%, and butyric acid is 0.05%. Finally, the corresponding ingredient ratio of the microecological regulation drug is generated.

[0083] S15: According to the ingredient ratio of the microecological regulation drug, use an automated batching system to mix the probiotic strain seed liquid, prebiotic components and short-chain fatty acids to generate a mixed liquid of the drug to be fermented and regulated, and send it to a fermentation tank.

[0084] In the embodiment of the present invention, according to the best ingredient ratio of the microecological regulation drug, an automated batching system is used to prepare the drug. The batching system consists of multiple high-precision automated liquid handling units, which can achieve precise mixing of the probiotic seed liquid, prebiotic components and short-chain fatty acids. During the operation, first, according to the determined ratio, the automated system extracts the corresponding components from the pre-prepared prebiotic raw material and short-chain fatty acid storage tanks, pumps them to the mixing tank, and the probiotic seed liquid is transported to the mixing system through a vacuum extraction system. In the mixing tank, various components will be mixed by high-speed stirring to ensure their uniform distribution. During this process, the temperature, pH value and other environmental conditions will be strictly controlled to maintain the activity of the probiotics. After mixing, the mixed liquid of the drug will be transported to the fermentation tank for fermentation treatment. The parameters such as temperature, humidity and ventilation volume in the fermentation tank are adjusted by an intelligent control system to ensure the best strain growth and short-chain fatty acid production during the fermentation process. Finally, the mixed liquid of the drug to be fermented and regulated is generated and sent into the fermentation tank for corresponding fermentation.

[0085] Further, the fermentation unit of the regulating drug includes the following functions:

[0086] Obtain the chemical components and microbial metabolic pathways corresponding to each active component from the mixed liquid of the drug to be fermented, and determine the proportion of nutrient components such as carbon source, nitrogen source and trace elements corresponding to the mixed liquid of the drug to be fermented during the fermentation process based on the chemical components and microbial metabolic pathways corresponding to each active component, so as to generate the proportion of nutrient components for microbial metabolic fermentation.

[0087] Using a fermenter, the microbial growth fermentation treatment is carried out on the fermentation-adjusting drug mixture to be fermented according to the proportion of microbial metabolic fermentation nutrients, so as to record the microbial metabolic fermentation process of generating the microecological regulating drug;

[0088] Through the microbial metabolic fermentation process of the microecological regulating drug, the corresponding microbial biomass growth rate and metabolite concentration in the fermentation process are obtained, and based on the microbial biomass growth rate and metabolite concentration, the microbial metabolic growth analysis of the microbial metabolic fermentation process of the microecological regulating drug is carried out to generate the microbial metabolic growth curve of the microecological regulating drug;

[0089] Different fermentation culture stages are divided through the microbial metabolic growth curve of the microecological regulating drug, and based on different fermentation culture stages, the drug active ingredient accumulation analysis of the microbial metabolic fermentation process of the microecological regulating drug is carried out to generate the microecological regulating drug active ingredient metabolic accumulation amount corresponding to different fermentation stages;

[0090] Based on the microecological regulating drug active ingredient metabolic accumulation amount corresponding to different fermentation stages, the programmable logic controller is used to segmentally and dynamically control the fermentation conditions such as temperature, pH and dissolved oxygen corresponding to each fermentation stage in the fermentation process to obtain the microecological regulating drug fermentation active ingredient.

[0091] As an embodiment of the present invention, refer to Figure 3 As shown, it is Figure 1 the functional flow schematic diagram of the regulating drug fermentation unit in

[0092] S21: Obtain the chemical components and microbial metabolic pathways corresponding to each active component through the fermentation-adjusting drug mixture to be fermented, and based on the chemical components and microbial metabolic pathways corresponding to each active component, determine the nutrient component ratio of the carbon source, nitrogen source and trace elements corresponding to the fermentation-adjusting drug mixture to be fermented in the fermentation process to generate the microbial metabolic fermentation nutrient component ratio;

[0093] In an embodiment of the present invention, the regulatory drug mixture to be fermented is analyzed by high performance liquid chromatography (HPLC) or gas chromatography - mass spectrometry (GC - MS) to qualitatively and quantitatively determine the chemical components of each active component in the mixture, including polysaccharides, amino acids, lipids, etc. By analyzing the molecular structure and chemical properties of each active component, the corresponding microbial metabolic pathways are further deduced. For example, carbohydrates and amino acid compounds can be converted into metabolites by specific microorganisms through glycolysis or amino acid metabolic pathways. According to the information of the metabolic pathways, metabolic engineering tools such as Metabolic Pathway Databases (e.g., KEGG, MetaCyc) are used to model the metabolic network. According to this model, the proportions of carbon sources (such as glucose, sucrose), nitrogen sources (such as ammonium salts, urea), and trace elements (such as zinc, copper, iron, etc.) required during fermentation are calculated to optimize the nutrient components of the mixture, and the proportion of fermentation nutrient components suitable for microbial metabolism is generated through mathematical models and calculation formulas, specifically, the carbon source accounts for 2% - 5% of the total fermenter, the nitrogen source accounts for 0.5% - 1% of the total fermenter, and the trace elements are 5 - 100 μg / L, and finally the proportion of fermentation nutrient components for microbial metabolism is determined.

[0094] S22: Use a fermenter to perform microbial growth fermentation treatment on the regulatory drug mixture to be fermented according to the proportion of fermentation nutrient components for microbial metabolism, and record the generation of the microecological regulatory drug metabolic fermentation process;

[0095] In an embodiment of the present invention, after configuring the regulatory drug mixture to be fermented and its corresponding nutrient components according to the previously calculated proportion of fermentation nutrient components for microbial metabolism using a fermenter, the fermenter should be a device with monitoring functions such as temperature, pH, dissolved oxygen, etc., and be adjusted according to the designed fermentation conditions (such as the temperature is set at 37°C and the pH is set at 6.5). During the fermentation process, parameters such as the temperature, pH value, and dissolved oxygen concentration in the fermenter are monitored in real time and dynamically adjusted according to the preset conditions. The fermentation broth samples are collected regularly by an automatic sampling device to analyze the growth status of microorganisms and the changes in metabolites therein. During the fermentation process, the microbial biomass at each time point (for example, by turbidity measurement or cell counting method) and the production amount of drug regulatory components (such as polysaccharides, active peptides) are recorded, and the microecological regulatory drug metabolic fermentation process is generated through real - time monitoring and recording.

[0096] S23: Obtain the corresponding microbial biomass growth rate and metabolite concentration during the fermentation process through the microecological regulatory drug metabolic fermentation process, and perform microbial metabolic growth analysis on the microecological regulatory drug metabolic fermentation process based on the microbial biomass growth rate and metabolite concentration to generate a microecological regulatory drug metabolic growth curve;

[0097] In the embodiments of the present invention, the biomass growth rate of microorganisms during the fermentation process is monitored in real time by experimental equipment. The specific operation is to use an optical density meter (OD600) to monitor the growth of microorganisms in the fermentation broth, sample regularly (such as every 2 hours), measure the optical density value in the sample, and convert it into the biomass concentration of microorganisms using a calibration curve. In addition, it is also necessary to measure the metabolite concentrations in the fermentation broth, such as lactic acid, acetic acid, glucose, etc., by analytical means such as HPLC and GC-MS. Based on these data, a mathematical model is used to fit the growth curve of microorganisms. Commonly used microbial growth models (such as the Monod model, Logistic model, etc.) are usually used for analysis, and according to the changes in the biomass growth rate of microorganisms and the metabolite concentrations, a metabolic growth curve of the microecological regulatory drug is plotted. This curve helps to evaluate the growth conditions, metabolic characteristics, and generation trends of active ingredients of microorganisms in different fermentation stages, and finally generates a metabolic growth curve of the microecological regulatory drug (such as Figure 5 shown).

[0098] S24: Different fermentation culture stages are divided through the metabolic growth curve of the microecological regulatory drug, and based on different fermentation culture stages, an analysis of the accumulation of active ingredients of the microecological regulatory drug during the metabolic fermentation process is carried out to generate the metabolic accumulation amount of the active ingredients of the microecological regulatory drug corresponding to different fermentation stages;

[0099] In the embodiments of the present invention, according to the generated metabolic growth curve of the microecological regulatory drug, the fermentation process is divided into multiple different stages, such as the growth lag phase, logarithmic growth phase, stationary phase, etc. Within each stage, the growth rate, metabolic activity, and accumulation amount of active ingredients of microorganisms are all different. In the growth lag phase, microorganisms mainly absorb exogenous carbon and nitrogen sources for cell proliferation, and at this time, the active ingredients of the drug are less. When entering the logarithmic growth phase, the growth rate of microorganisms is the fastest, and the production amount of metabolites increases significantly. The stationary phase is when the accumulation of metabolites reaches a peak and begins to gradually stabilize. On this basis, by analyzing the changes in metabolite concentrations in each stage, the accumulation amount of active ingredients of the drug in each stage is evaluated. The specific methods include regular sampling and detecting the concentration of active ingredients in the fermentation broth by techniques such as HPLC and LC-MS, and combining the growth curve and metabolite data to finally generate the metabolic accumulation amount of the active ingredients of the microecological regulatory drug corresponding to different fermentation stages.

[0100] S25: Based on the metabolic accumulation amount of the active ingredients of the microecological regulatory drug corresponding to different fermentation stages, the temperature, pH, and dissolved oxygen fermentation conditions corresponding to each fermentation stage during the fermentation process are controlled in a segmented and dynamic manner by a programmable logic controller to obtain the active ingredients of the microecological regulatory drug fermentation.

[0101] In the embodiments of the present invention, by combining the metabolic accumulation amounts of the drug active ingredients in each fermentation stage obtained previously, a programmable logic controller (PLC) is used to dynamically control the key fermentation conditions (such as temperature, pH, dissolved oxygen) of the fermenter in a segmented manner. In the lag phase, the temperature is reduced, the pH value is controlled, and the dissolved oxygen level is reduced to promote the adaptive growth of microorganisms. In the logarithmic growth phase, the temperature is appropriately increased, and the pH and dissolved oxygen concentration are adjusted to accelerate the proliferation of microorganisms and the accumulation of metabolites. When entering the stationary phase, a constant temperature and pH value are maintained, and the supply of dissolved oxygen is optimized to ensure the maximum accumulation of active ingredients. The PLC system will achieve precise dynamic regulation according to the preset fermentation process control parameters to ensure that the best growth and metabolic conditions are reached in each fermentation stage, and finally obtain the fermentation active ingredients of the microecological regulation drug.

[0102] Further, the regulating drug processing and preparation unit includes the following functions:

[0103] A directional cooling device is used to control the cooling rate not exceeding 2°C per minute to perform a preliminary thermal temperature cooling treatment on the fermentation active ingredients of the microecological regulation drug, obtaining a temperature-pretreated microecological regulation drug mixture.

[0104] In the embodiments of the present invention, by using a directional cooling device to control the cooling rate of the fermentation active ingredients of the microecological regulation drug, it is ensured that the cooling process does not exceed 2°C per minute. Specifically, a cooling device with an adjustable cooling rate is used during implementation, such as a laminar cooling tower or a cooling water tank with a precise temperature control system. A temperature sensor is provided in the cooling device to monitor the temperature change of the drug mixture in real time to ensure the stability of the cooling process. After the drug fermentation liquid or solution enters the cooling area, the control system automatically adjusts the flow rate of the cooling medium (such as cooling water or coolant) to reduce its temperature, but not exceeding the set maximum cooling rate of 2°C / min, thereby avoiding the damage to the active ingredients caused by excessive cooling. During this process, the precise control of the cooling rate helps to maintain the stability of the microecological components and avoid crystallization or inactivation of the active ingredients during the cooling process, and finally obtain a temperature-pretreated microecological regulation drug mixture.

[0105] Preferably, a step-by-step low-temperature freezing treatment is performed on the temperature-pretreated microecological regulation drug mixture by controlling the freezing temperature between -30°C and -50°C through a segmented low-temperature pre-freezing technique, obtaining the microecological regulation low-temperature frozen drug components.

[0106] In the embodiments of the present invention, the temperature pre-microecological regulation drug mixture components are gradually cryogenically treated by adopting a segmented low-temperature pre-freezing technique, so as to perform temperature segmentation treatment on the drug mixture components through a cryogenic freezing device, ensuring that the freezing temperature is maintained between -30°C and -50°C. The freezing device used is a freezing tunnel or a freezer, which is provided with multiple temperature control regions and can accurately adjust the freezing temperature at each stage. In the initial pre-cooling stage, the temperature of the drug mixture components gradually decreases to about -30°C, and then enters a transition stage with a slower freezing rate, and the drug mixture components are frozen to -50°C. During this process, a temperature monitoring system is used to monitor the freezing environment in real time to ensure that the temperature control error does not exceed ±1°C. This segmented freezing process can effectively prevent large ice crystals from forming in the drug components under rapid freezing, thereby avoiding damage to the microecological active components of the drug and ensuring its stability and biological activity. Finally, the microecological regulation cryogenically frozen drug components are obtained.

[0107] Preferably, the microecological regulation cryogenically frozen drug components are subjected to vacuum drying optimization treatment to obtain the microecological regulation freeze-dried drug components;

[0108] In the embodiments of the present invention, the microecological regulation cryogenically frozen drug components that have been cryogenically frozen previously are dried in a vacuum environment, aiming to remove the moisture in the drug while maintaining the microecological active components of the drug. Specifically, when operating, the microecological regulation cryogenically frozen drug components are placed in a vacuum drying oven, and the vacuum degree in the oven is adjusted to between 0.01 - 0.05 Pa. In order to improve the drying efficiency, a heating plate or a circulating hot air system can be used to moderately heat the drug, but the heating temperature must be strictly controlled between 30 - 40°C to avoid thermal degradation of the drug components due to too high a temperature. The temperature and pressure during the drying process are monitored in real time, and the heating and vacuum degree are automatically adjusted through a PLC control system to ensure that the drug slowly loses water in a vacuum environment, avoiding contamination of the drug quality by external gases, and at the same time ensuring that the drug finally presents a relatively stable dried form. Finally, the microecological regulation freeze-dried drug components are obtained.

[0109] Preferably, the microecological regulation freeze-dried drug components are subjected to drug concentration treatment to obtain the microecological regulation highly concentrated drug components;

[0110] In the embodiments of the present invention, the microecological regulation freeze-dried drug components after prior drying are concentrated by using membrane separation technology or an evaporation concentration device. During specific operation, after the microecological regulation freeze-dried drug components are dissolved, they are fed into a multi-stage membrane filtration device (such as an ultrafiltration membrane or a reverse osmosis membrane). This device can remove moisture and soluble small-molecule substances in the solution through step-by-step filtration, thereby concentrating the drug components. During this process, a precise control system is used to adjust the fluid flow rate and filtration pressure to ensure the efficiency and stability of the concentration process. To further improve the concentration efficiency, a temperature control heating system can be used to control the solution temperature between 40°C and 50°C while maintaining the cleanliness and stability of the membrane. During the concentration process, the drug components will be concentrated to the required concentration under certain temperature and pressure conditions, and finally, the highly concentrated microecological regulation drug components are obtained.

[0111] Preferably, the highly concentrated microecological regulation drug components are microencapsulated to obtain microecological regulation microencapsulated drug components.

[0112] In the embodiments of the present invention, the highly concentrated microecological regulation drug components are embedded in a suitable carrier material (such as polymers, liposomes, etc.) by using the solvent evaporation method or the spray drying method. During specific implementation, the concentrated drug components and the carrier material are mixed in a certain proportion to form a uniform solution or emulsion, and the solution is sprayed into the drying air stream through a high-pressure sprayer. The solvent evaporates rapidly, and the drug components are embedded in tiny particles to form microencapsulated drugs. During the microencapsulation process, the operating temperature needs to be strictly controlled between 30°C and 50°C to avoid loss of drug components caused by too high a temperature. This microencapsulation process ensures that the drug components can be slowly released or targeted released through the protection of the carrier material. The microencapsulated drug components can be subjected to subsequent packaging and sub-packaging processes, and finally, the microecological regulation microencapsulated drug components are obtained.

[0113] Furthermore, the vacuum drying optimization treatment for the microecological regulation cryogenic freeze-dried drug components includes:

[0114] Obtaining the solubility corresponding to each drug active ingredient in the microecological regulation cryogenic freeze-dried drug components;

[0115] In the embodiments of the present invention, in order to achieve the goal of obtaining the solubility of each drug active ingredient, a sample of the drug active ingredient is selected for solubility determination. Specifically, the solvent system of the target drug is first selected, and a standard solubility determination procedure is established. Commonly used methods include the static method, the dynamic method, the photometric method, or using the solubility curve to calculate the solubility of the drug under different temperature and pressure conditions. The solubility is quantitatively analyzed by high performance liquid chromatography (HPLC) or ultraviolet-visible spectrophotometry (UV-VIS) to obtain the solubility value of the drug under specific temperature and solvent conditions. The solubility of the drug directly affects the retention and inactivation of the drug components during the subsequent vacuum drying process, and finally the solubility corresponding to each drug active ingredient is obtained.

[0116] Preferably, during the vacuum drying process of the microecological regulation cryogenic frozen drug components, a trace amount of inert gas is introduced to guide the direction of the molecular flow of the drug components, and based on the solubility corresponding to each drug active ingredient, a drying solubility loss calculation formula is used to quantitatively calculate the loss during the vacuum drying process of the microecological regulation cryogenic frozen drug components, so as to obtain the drying solubility loss of the drug active ingredient;

[0117] In the embodiments of the present invention, during the vacuum drying process of the microecological regulation cryogenic frozen drug components, a trace amount of inert gas is introduced to guide the direction of the molecular flow of the drug components, ensuring that the drug active ingredient maximally retains its activity during the vacuum drying process. In the vacuum drying equipment, first, the microecological regulation cryogenic frozen drug components are placed in the vacuum drying chamber, the initial vacuum degree is set, and the cooling system is started for cryogenic freezing treatment. At this time, a trace amount of inert gas (such as nitrogen or helium) is introduced into the equipment, and the flow characteristics of the inert gas are used to control the direction of the molecular flow of the drug components. The flow rate of the inert gas is adjusted by a precision flow meter and maintained within the set range. At the same time, by combining the total duration of the drying process, the solubility corresponding to the drug active ingredient, the initial solubility before drying, the drug component concentration, the concentration solubility loss influence coefficient, the vacuum pressure of the drying environment, the drying environment temperature, the drying environment humidity, and related parameters, a suitable drying solubility loss calculation formula is formed to quantitatively calculate the solubility loss, so as to estimate the solubility loss of the drug molecules during the drying process through the dynamic changes of the solubility of the known drug and the gas flow, and finally obtain the drying solubility loss of the drug active ingredient.

[0118] Preferably, based on the drying solubility loss of the drug active ingredient, the vacuum drying process of the microecological regulation cryogenic frozen drug components is optimized, and the contact ratio between the flow rate of the inert gas and the microecological regulation cryogenic frozen drug components is precisely controlled to obtain the microecological regulation freeze-dried drug components.

[0119] In the embodiments of the present invention, after obtaining the solubility loss of the drug active ingredient, the vacuum drying process of the microecological regulation cryogenic freezing drug is optimized. First, according to the calculated solubility loss, the working parameters of the vacuum drying equipment are adjusted. Specifically, based on the solubility and the existing loss amount of the drug active ingredient, appropriate vacuum degree, temperature, and inert gas flow rate are set, so that the drug active ingredient can maintain its activity to the greatest extent during the drying process. The core of the optimization process is to precisely control the contact ratio of the inert gas flow rate and the drug component, ensuring that the direction of the gas flow guidance is consistent with the movement direction of the drug molecules, thereby reducing the loss of the drug during the drying process. At this time, a high-precision flow control system is used to monitor and adjust the gas flow rate in real time, ensuring that the contact time between the gas flow rate and the drug molecules and the temperature curve remain in an ideal state. Through repeated adjustment and monitoring, the drying effect is optimized, ensuring that the quality and activity of each dose of drug component meet the standard requirements, and finally obtaining the microecological regulation freeze-dried drug component.

[0120] Further, the specific formula for calculating the drying solubility loss is as follows:

[0121]

[0122] In the formula, ΔL(t) is the drying solubility loss of the drug active ingredient at time t, T is the total duration of the drying process, n is the total number of drug active ingredients, i is the item index of the drug active ingredient, S i (t) is the solubility corresponding to the i-th drug active ingredient at time t, is the initial solubility of the i-th drug active ingredient before drying, C i (t) is the drug component concentration corresponding to the i-th drug active ingredient at time t, α i is the concentration solubility loss influence coefficient corresponding to the i-th drug active ingredient, P(t) is the vacuum pressure of the drying environment at time t, W(t) is the temperature of the drying environment at time t, H(t) is the humidity of the drying environment at time t, and η is the correction coefficient of the drying solubility loss of the drug active ingredient.

[0123] The present invention obtains a drying solubility loss calculation formula through the use of a specific mathematical model and verification, which is used to quantitatively calculate the loss in the vacuum drying process corresponding to the microecological regulation cryogenic freezing drug components. By precisely considering multiple factors such as solubility, concentration, pressure, temperature, humidity, etc. of the drying environment, this drying solubility loss calculation formula can quantify the solubility loss of the drug active ingredients during the drying process. This is crucial for ensuring that the drug does not lose its active ingredients during the drying process and maintaining its activity. Especially for cryogenic freezing drugs, the accurate calculation of solubility loss can effectively prevent the reduction of drug efficacy caused by improper drying processes. The formula not only considers the solubility and concentration of each drug active ingredient but also introduces the influence coefficient between the components. Therefore, it can accurately reflect the synergistic effect or interaction of multi-component drugs during the drying process. This refined consideration makes the formula more applicable to complex drug formulation systems, especially microecological regulation drugs. The environmental factors (such as vacuum pressure, temperature, humidity) during the drying process are fully reflected in the formula, which enables the dynamic adjustment of drying parameters and real-time calculation of solubility loss under different drying environments. This is very important for real-time monitoring of the drying process and ensuring that the drug components are dried under optimal conditions. By calculating the drying solubility loss and cooperating with the design of guiding molecular flow through inert gas, the flow rate of the inert gas can be precisely controlled, optimizing the drying process of microecological regulation drugs. The optimization of this process can reduce solubility loss, avoid the quality decline of drug components caused by over-drying, and ensure the quality stability of the drug. By quantitatively calculating and optimizing the solubility loss of each drug active ingredient, the component loss caused by the non-uniformity during the drying process can be effectively reduced, which helps to improve the uniformity and stability of drug formulations between batches and ensure the reliability of the final product quality. In addition, the introduction of a correction coefficient makes the formula more flexible, enabling adjustment according to the actual situations of different drugs, drying equipment, gas flow rates, etc., compensating for the factors that may not be fully covered in theoretical calculations. It provides a space for dynamic adjustment, making the calculation of solubility loss during the drying process closer to the actual application environment, enabling the optimization and adjustment of the vacuum drying process, reducing unnecessary drug component losses, and improving the drying efficiency. In summary, the formula fully considers the drying solubility loss ΔL(t) of the drug active ingredients at time t, the total duration T of the drying process, the total number n of drug active ingredients, the item index i of the drug active ingredients, the solubility S i (t) of the i-th drug active ingredient at time t, the initial solubility S 0i of the i-th drug active ingredient before drying, the drug component concentration C i (t) of the i-th drug active ingredient at time t, and the concentration solubility loss influence coefficient α i, the corresponding vacuum pressure P(t) of the drying environment at time t, the corresponding drying environment temperature W(t) at time t, the corresponding drying environment humidity H(t) at time t, the correction coefficient η of the drying solubility loss of the drug active ingredient, and a functional relationship is formed according to the mutual correlation relationship between the drying solubility loss ΔL(t) of the drug active ingredient at time t and the above parameters. This formula can realize the loss quantification calculation process of the vacuum drying process corresponding to the microecological regulation cryogenic freezing drug components. At the same time, by introducing the correction coefficient η of the drying solubility loss of the drug active ingredient, it can be adjusted according to the error situation in the calculation process, thereby improving the accuracy and applicability of the drying solubility loss calculation formula.

[0124] Furthermore, the microencapsulation preparation of the highly concentrated drug components for microecological regulation includes:

[0125] Obtain plant capsule excipients, and perform pre-treatment for microencapsulation compatibility on the highly concentrated drug components for microecological regulation based on the plant capsule excipients to obtain a stable matrix mixed component of the microecological regulation drug.

[0126] In the embodiments of the present invention, by selecting suitable plant capsule excipients, such as natural polysaccharide substances of plant origin such as gelatin, gum arabic or xanthan gum, the selected excipients need to have excellent biocompatibility and biodegradability to ensure that they are non-toxic to the human body. The plant capsule excipients are made compatible with the microecological regulation drug components required by diabetic patients according to their different properties. The specific operation is to first weigh a certain mass of plant capsule excipients, dissolve them in an appropriate amount of deionized water, heat to 60 °C using a magnetic stirrer or a high-speed shear mixer, and continuously stir to ensure that the excipients are completely dissolved or dispersed. Then add the treated microecological regulation drug components into the solution, adjust the pH value to between 5.5 and 6.5, and use an oscillator or an ultrasonic processor to homogenize the mixed solution to ensure that the drug components are evenly distributed in the excipients to form a uniform pre-treatment mixed solution. During this process, the stirring speed and time should be controlled to avoid degradation of the drug components caused by high temperature or high shear rate, and finally obtain a stable matrix mixed component of the microecological regulation drug.

[0127] Preferably, use poly(lactic-co-glycolic acid) to perform microencapsulation on the stable matrix mixed component of the microecological regulation drug to generate a preliminary particle component of the microencapsulated drug for microecological regulation.

[0128] In an embodiment of the present invention, by selecting a suitable poly(lactic-co-glycolic acid) (PLGA), due to its good biodegradability and biocompatibility, it is suitable for encapsulating microencapsulated drugs. The molecular weight of PLGA should be selected to ensure that its degradation rate in vivo can match the drug release requirements. The specific operation is to take an appropriate amount of PLGA and dissolve it in solvents such as chloroform and ethyl acetate to obtain a solution with a certain concentration. Then, the previously obtained microecological regulatory drug stable matrix mixture is added to the PLGA solution, and emulsification treatment is carried out through a high-speed shear emulsification device or an ultrasonic emulsification device to form a microencapsulated emulsion. During the emulsification process, by adjusting the emulsification time, temperature, and shear force, the particle size distribution and drug loading of the microcapsules can be controlled. During the emulsification process, if necessary, auxiliaries such as surfactants (such as cetyltrimethylammonium bromide) can be used to stabilize the emulsion and prevent droplet aggregation or uneven particle size. After emulsification is completed, the emulsion is dropped into a previously prepared hardening solution (such as calcium chloride solution or solvent evaporation method solution) to solidify the PLGA polymer to form microencapsulated particles. Through centrifugal separation, excess solvents and impurities are removed, and finally, the preliminary particle components of the microecological regulatory microencapsulated drug are generated.

[0129] Preferably, the preliminary particle components of the microecological regulatory microencapsulated drug are subjected to supercritical fluid drying treatment to obtain the microecological regulatory microencapsulated drug components.

[0130] In an embodiment of the present invention, by selecting an appropriate supercritical fluid drying technique (such as supercritical CO2 drying), it can remove the solvent in the microencapsulated particles without damaging the drug activity, effectively reduce the volume of the particles, and improve the stability of the drug. The specific operation is to put the previously obtained preliminary microencapsulated drug particles into a supercritical drying device, set appropriate operating temperatures (such as 40 - 60 °C) and pressures (about 10 - 30 MPa). In a supercritical CO2 environment, by adjusting parameters such as fluid flow rate, temperature, and pressure, CO2 exchanges with the internal solvent of the particles in the supercritical state, thereby removing the organic solvent in the microcapsules and avoiding drug degradation or particle size changes caused by traditional drying methods. The drying process continues until the residual solvent content in the particles reaches the required extremely low level (usually not exceeding 0.1%). After this process ends, by reducing the pressure, CO2 returns to its normal state, and the dried microecological regulatory microencapsulated drug components are collected. This step can effectively maintain the morphology and activity of the microencapsulated drug, ensure good stability of the drug during subsequent packaging and storage, and finally obtain the microecological regulatory microencapsulated drug components.

[0131] Furthermore, the drug automatic packaging unit includes the following functions:

[0132] Obtain the microecological regulatory drug requirements corresponding to different specifications;

[0133] In the embodiments of the present invention, by analyzing in detail the demand for microecological regulation drugs of diabetic patients, the determination of the demand is based on the patient's constitution, disease stage, drug concentration requirements, etc., and in combination with the drug prescription requirements of clinical medicine, the demand for drugs of different specifications is determined. For example, diabetic patients need different doses of microecological regulation drugs at different treatment stages, such as microencapsulated probiotic preparations. Through the medical data acquisition system, big data analysis is carried out on the patient's medical record data, and in combination with the pharmacological effects and dosing regimens of the drugs, the required drug specifications (such as the dose taken each time, the dosing frequency per week, etc.) are further determined. At this time, the determined specifications include small doses (such as 500 mg), medium doses (such as 1000 mg), and large doses (such as 2000 mg), and the microecological regulation drug specifications suitable for the needs of different diabetic patients are finally obtained, and the microecological regulation drug demands corresponding to different specifications are obtained.

[0134] Preferably, based on the microecological regulation drug demands corresponding to different specifications, the dispensing doses of the microecological regulation microencapsulated drug components are determined to generate the microecological regulation drug dispensing doses corresponding to different specifications;

[0135] In the embodiments of the present invention, by determining the dispensing doses of the previously prepared microecological regulation microencapsulated drug components according to the previously obtained drug demands, the microecological regulation drug components usually exist in the form of microcapsules and can release probiotics or other beneficial components in the intestine. Therefore, when dispensing the drugs, it is necessary to consider the stability, release characteristics of the microencapsulated drugs and the specific needs of the patients, and use precise weighing equipment to measure each microencapsulated drug component, and use an automated dispensing device to achieve the dispensing of drugs of different specifications. For example, for patients who need a dose of 1000 mg, the drug will be dispensed into each drug package containing 1000 mg of microencapsulated components according to the quality standard of the microencapsulated components. Through the linkage of multiple automated devices, the precise dispensing of drugs of different specifications (such as 500 mg, 1000 mg, 2000 mg, etc.) is achieved, and finally the microecological regulation drug dispensing doses corresponding to different specifications are generated.

[0136] Preferably, based on the microecological regulation drug dispensing doses corresponding to different specifications, the microecological regulation microencapsulated drug components are subjected to automated controlled dispensing treatment using cold chain technology to obtain the microecological regulation dispensed dose drugs;

[0137] In the embodiments of the present invention, after the dispensing of the microecological regulatory drugs corresponding to different specifications obtained through the combination of previous analyses is completed, the cold chain technology is adopted for the treatment of the dispensed drugs. The cold chain technology is to ensure the stability of the microecological regulatory drugs after dispensing and prevent the drug components, especially the microencapsulated probiotics, from being inactivated or degraded due to the increase in temperature. In specific operations, through the cold chain logistics method, and using a temperature-controlled dispensing room or automated dispensing equipment for drug dispensing, the temperature in the cold chain dispensing equipment is strictly controlled between 2°C and 8°C to ensure that the activity of the microencapsulated drug components is not affected by the external environment. The dispensed drugs will be packaged through a temperature control system to facilitate maintaining the appropriate temperature of the drugs during subsequent storage and transportation. With the support of the automated control system, the dispensing process will be accurate to each unit drug dose to ensure the consistency and accuracy of the final drug specifications, and finally, the microecological regulatory dispensed dose drugs will be obtained.

[0138] Preferably, the microecological regulatory dispensed dose drugs are subjected to modified atmosphere packaging treatment by using temperature-controlled packaging materials and adjusting the inert gas components in the package to generate microecological regulatory modified atmosphere packaging drugs.

[0139] In the embodiments of the present invention, through the modified atmosphere packaging treatment of the already dispensed microecological regulatory drugs, the modified atmosphere packaging technology can effectively prevent the drug components from being affected by moisture, oxidation or deterioration during storage and transportation. In specific implementation, first, select the temperature-controlled packaging materials suitable for the microecological regulatory drugs, usually high-performance film materials with good air permeability and barrier properties. These materials can prevent the influence of the external environment on the drugs while controlling the temperature. The packaging machine dispenses the drugs into the pre-set packaging bags, and then through the inert gas mixing system, specific proportions of inert gases such as nitrogen and carbon dioxide are filled into the interior of the packaging bags. This process can ensure that the oxygen content inside the packaging bags is reduced to a relatively low level, thereby inhibiting the growth of microorganisms and maintaining the active ingredients of the microecological regulatory drugs. During the packaging process, by strictly controlling the time of gas filling and the proportion of gas components, it is ensured that each bag of drugs can be stored in the best environment, and finally, the microecological regulatory modified atmosphere packaging drugs are generated.

[0140] The above are only the specific implementation manners of the present invention, enabling those skilled in the art to understand or implement the present invention. Various modifications to these embodiments will be obvious to those skilled in the art. The general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but will conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. An integrated system for preparing and packaging microecological regulation drugs for diabetic patients, characterized in that: The following units are included: The drug raw material preparation unit is used to select clinically verified probiotic strains, including lactic acid bacteria and bifidobacteria, and conduct experimental ingredient analysis on the probiotic strains and pre-prepared prebiotic components and short-chain fatty acids to generate the proportion of microecological drug ingredients; According to the proportion of microecological regulating drug ingredients, the probiotic strains, prebiotic components and short-chain fatty acids are mixed using an automated batching system to generate a fermented regulating drug mixture, which is then sent to a fermentation tank; The regulating drug fermentation unit is used to use a fermentation tank to carry out microbial growth fermentation on the fermented regulating drug mixture, and to dynamically control the corresponding temperature, pH and dissolved oxygen fermentation conditions during the fermentation process in a segmented manner through a programmable logic controller to obtain the active fermentation ingredients of the microecological regulating drug; The regulating drug processing and preparation unit is used to perform low-temperature freeze-drying treatment on the fermented active ingredients of the microecological regulating drug to obtain the microecological regulating freeze-dried drug ingredients; perform drug concentration and microencapsulation preparation on the microecological regulating freeze-dried drug ingredients to obtain the microecological regulating microencapsulated drug ingredients; The drug automated packaging unit is used to obtain the demand for microecological regulation drugs corresponding to different specifications, and based on the demand for microecological regulation drugs corresponding to different specifications, the cold chain technology is used to perform automated controlled packaging of microecological regulation microencapsulated drug components to obtain microecological regulation packaged dosage drugs; The microecologically regulated divided-dose drugs are subjected to modified atmosphere packaging treatment to produce microecologically regulated modified atmosphere packaging drugs.

2. The integrated system for preparing and packaging microecological regulation drugs for diabetic patients according to claim 1, characterized in that: The drug raw material preparation unit includes the following functions: By selecting clinically verified probiotic strains, including lactic acid bacteria and bifidobacteria, and selecting, screening and dissolving the probiotic strains to obtain a probiotic strain seed liquid; Based on the pre-prepared prebiotic components and short-chain fatty acids, the strain interaction effect analysis of the corresponding probiotic strains is performed, wherein the prebiotic components include dietary fiber and oligosaccharides, and the short-chain fatty acids include acetic acid, propionic acid and butyric acid, so as to generate different prebiotic and short-chain fatty acid combination-strain interaction effect maps; Based on the different prebiotic and short-chain fatty acid combination-strain interaction effect maps, the experimental ingredients of probiotic strain seed liquid, prebiotic components and short-chain fatty acids were analyzed to generate an experimental table of active ingredients of microbial regulation drugs; According to the experimental table of active ingredients of microbial regulation drugs, select the combination of ingredient ratios that best corresponds to the microecological regulation effect to generate the ingredient ratios of microecological regulation drugs; According to the proportion of microecological regulating drug ingredients, the probiotic strain seed liquid, prebiotic components and short-chain fatty acids are mixed using an automated batching system to generate a fermented regulating drug mixture, which is then sent to a fermentation tank.

3. The integrated system for preparing and packaging microecological regulation drugs for diabetic patients according to claim 2, characterized in that: The specific proportion of ingredients of the microecological regulation drug is 1×10 6 CFU / mL of lactic acid bacteria and bifidobacteria, 0.4% of dietary fiber, 0.3% of oligosaccharides, 0.1% of acetic acid and 0.05% of butyric acid.

4. The integrated system for preparing and packaging microecological regulation drugs for diabetic patients according to claim 1, characterized in that: The drug fermentation regulating unit includes the following functions: Obtaining chemical components and microbial metabolic pathways corresponding to each active component from the fermented drug mixture, and determining the nutrient ratio of carbon source, nitrogen source and trace elements corresponding to the fermented drug mixture during the fermentation process based on the chemical components and microbial metabolic pathways corresponding to each active component, so as to generate a microbial metabolic fermentation nutrient ratio; Using a fermentation tank to carry out microbial growth fermentation treatment on the mixed solution of the fermented regulating drugs according to the proportion of microbial metabolic fermentation nutrients, so as to record the metabolic fermentation process of the generated microecological regulating drugs; The corresponding microbial biomass growth rate and metabolite concentration in the fermentation process are obtained through the microecological regulation of drug metabolism fermentation process, and the microbial metabolic growth analysis of the microecological regulation of drug metabolism fermentation process is performed based on the microbial biomass growth rate and metabolite concentration to generate a microecological regulation of drug metabolism growth curve; Different fermentation culture stages are divided by the growth curve of microecological drug metabolism, and the accumulation analysis of drug active ingredients in the fermentation process of microecological drug metabolism is performed based on different fermentation culture stages to generate the metabolic accumulation of active ingredients of microecological drug regulation corresponding to different fermentation stages; Based on the metabolic accumulation of the active ingredients of the microecological regulating drugs corresponding to different fermentation stages, the programmable logic controller is used to dynamically control the temperature, pH and dissolved oxygen fermentation conditions corresponding to each fermentation stage in the fermentation process in a segmented manner to obtain the active ingredients of the microecological regulating drugs fermentation.

5. The integrated system for preparing and packaging microecological regulation drugs for diabetic patients according to claim 4, characterized in that: The microbial metabolic fermentation nutrient ratios in the fermenter correspond to the culture component ratios as follows: carbon source accounts for 2%-5% of the total fermenter, nitrogen source accounts for 0.5%-1% of the total fermenter, and trace elements are 5-100 μg / L.

6. The integrated system for preparing and packaging microecological regulation drugs for diabetic patients according to claim 1, characterized in that: The drug processing and preparation unit includes the following functions: A directional cooling device is used to control the cooling rate to not exceed 2°C per minute to perform preliminary thermal temperature cooling treatment on the active ingredients of the microecological regulation drug fermentation to obtain a temperature-prepared microecological regulation drug mixed component; The temperature pre-microecological regulation drug mixture components are gradually cryogenically frozen by controlling the freezing temperature between -30°C and -50°C through a segmented cryogenic pre-freezing technology to obtain a microecological regulation cryogenically frozen drug component; Performing vacuum drying optimization treatment on the microecological regulation low-temperature frozen drug components to obtain the microecological regulation freeze-dried drug components; Perform drug concentration treatment on the microecological regulation freeze-dried drug components to obtain microecological regulation high-efficiency concentrated drug components; The microecological regulation high-efficiency concentrated drug component is microencapsulated to obtain the microecological regulation microencapsulated drug component.

7. The integrated system for preparing and packaging microecological regulation drugs for diabetic patients according to claim 6, characterized in that: The vacuum drying optimization process for the microecological regulation low-temperature frozen drug components comprises: Obtain the solubility of each active ingredient in the cryogenically frozen drug component regulated by microecology; A trace amount of inert gas is introduced into the vacuum drying process corresponding to the low-temperature frozen drug components regulated by the microecology to guide the direction of the molecular flow of the drug components, and the loss of the vacuum drying process corresponding to the low-temperature frozen drug components regulated by the microecology is quantitatively calculated using the drying solubility loss calculation formula based on the solubility corresponding to each active drug component, so as to obtain the drying solubility loss of the active drug component; Based on the drying solubility loss of the active pharmaceutical ingredients, the vacuum drying process corresponding to the microecologically regulated low-temperature frozen pharmaceutical ingredients is optimized, and the contact ratio between the inert gas flow rate and the microecologically regulated low-temperature frozen pharmaceutical ingredients is precisely controlled to obtain the microecologically regulated freeze-dried pharmaceutical ingredients.

8. The integrated system for preparing and packaging microecological regulation drugs for diabetic patients according to claim 7, characterized in that: The drying solubility loss calculation formula is specifically: Where ΔL(t) is the drying solubility loss of the active pharmaceutical ingredient at time t, T is the total duration of the drying process, n is the total number of active pharmaceutical ingredients, i is the item index of the active pharmaceutical ingredient, and S i (t) is the solubility of the i-th active pharmaceutical ingredient at time t, is the initial solubility of the i-th active pharmaceutical ingredient before drying, C i (t) is the drug ingredient concentration corresponding to the i-th drug active ingredient at time t, α i is the concentration solubility loss influence coefficient corresponding to the i-th active pharmaceutical ingredient, P(t) is the vacuum pressure of the drying environment corresponding to time t, W(t) is the temperature of the drying environment corresponding to time t, H(t) is the humidity of the drying environment corresponding to time t, and η is the correction coefficient of the drying solubility loss of the active pharmaceutical ingredient.

9. The integrated system for preparing and packaging microecological regulation drugs for diabetic patients according to claim 6, characterized in that: The microencapsulation preparation of the highly efficient concentrated drug component for microecological regulation comprises: Obtaining plant encapsulation excipients, and performing microencapsulation compatibility pre-treatment on the microecological regulation high-efficiency concentrated drug components based on the plant encapsulation excipients to obtain a stable matrix mixed component of the microecological regulation drug; The microecological regulation drug stable matrix mixed components are microencapsulated by using polylactic acid-glycolic acid copolymer to generate the preliminary particle components of the microecological regulation drug microencapsulation; The preliminary particle components of the microecological regulation microencapsulated drug are subjected to supercritical fluid drying treatment to obtain the microecological regulation microencapsulated drug components.

10. The integrated system for preparing and packaging microecological regulation drugs for diabetic patients according to claim 1, characterized in that: The automated drug dispensing unit includes the following functions: Obtain the demand for microecological regulation drugs corresponding to different specifications; Based on the demand for microecological regulation drugs corresponding to different specifications, the drug specification packaging dosage of the microecological regulation microencapsulated drug components is determined to generate the microecological regulation drug packaging dosage corresponding to different specifications; Based on the microecological regulation drug sub-packaging dosages corresponding to different specifications, the microecological regulation microencapsulated drug components are automatically controlled and sub-packed using cold chain technology to obtain microecological regulation sub-packaging dosage drugs; Microecologically regulated modified atmosphere packaging drugs are produced by using temperature-controlled packaging materials and adjusting the inert gas composition in the packaging to carry out modified atmosphere packaging of microecologically regulated divided-dose drugs.

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