Method and system for enhancing dissolution of active ingredients of traditional Chinese medicine based on nanobubble diaphragm water

Abstract

The invention provides a traditional Chinese medicine active ingredient dissolution enhancing method and system based on nanometer bubble diaphragm water. The method is applied to the technical field of traditional Chinese medicine extraction and preparations, and comprises the following steps: preparing high-concentration nanobubble water, performing physicochemical property perception, and constructing to obtain a standardized nanobubble water sample; dynamically simulating the contact process with the traditional Chinese medicinal materials, and constructing to obtain multi-dimensional dissolution characteristic parameters; constructing a dissolution enhancement regulator, performing parameter coupling processing on the multi-dimensional dissolution characteristic parameters, and outputting to obtain a dissolution enhancement weight matrix; constructing to obtain a multi-mechanism weighted dissolution target function, respectively calculating to obtain multi-path fusion dissolution results under different preparation processes, and predicting the dissolution efficiency of the active components; and performing optimization and feedback control on the traditional Chinese medicine extraction process according to the prediction result of the dissolution efficiency of the active ingredients. In this way, the dissolution efficiency of the active ingredients of the traditional Chinese medicine and the process controllability can be remarkably improved.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine extraction and preparation technology, and in particular to a method and system for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble-based Ganlan water. Background Technology

[0002] With the continuous advancement of the modernization of traditional Chinese medicine, improving the dissolution efficiency of active ingredients in medicinal herbs has become a key technological bottleneck in enhancing efficacy, ensuring preparation quality, and achieving green pharmaceutical manufacturing. Traditional Chinese medicine often uses "Ganlan water"—water treated through repeated pouring and stirring—in the decoction process to enhance drug extraction.

[0003] Currently, some studies have attempted to introduce micro- and nano-bubble technology into the field of traditional Chinese medicine or natural product extraction. However, there are still some problems in the field of traditional Chinese medicine extraction: First, there is a lack of standardized preparation methods for highly stable nano-bubble water that are quantifiable and controllable based on the traditional concept of Ganlan water; second, there is insufficient systematic optimization and comparative research on the physicochemical properties of bubbles under different generation processes (such as cascading method, pressurized release method, and rotary evaporation method); and third, the mechanism of action between the physicochemical properties of nano-bubbles and their effect on the dissolution kinetics of active ingredients in traditional Chinese medicine has not yet been established.

[0004] Therefore, there is an urgent need for a scientific, controllable, and green method to enhance the dissolution of active ingredients in traditional Chinese medicine, which can both inherit the wisdom of traditional Chinese medicine in water use and integrate modern nanotechnology to achieve technological progress from experience to standards and from qualitative to quantitative analysis. Summary of the Invention

[0005] This invention provides a method and system for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble-infused water. By constructing highly stable, high-concentration nanobubble water as a green extraction medium and combining it with a multi-mechanism synergistic dissolution regulation strategy, it solves the technical problems of low dissolution efficiency of active ingredients, uncontrollable process, and lack of systematic integration of the physicochemical mechanism of nanobubbles in existing traditional Chinese medicine extraction technologies.

[0006] According to a first aspect of the present invention, a method for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble-based Ganlan water is provided, comprising the following steps:

[0007] High-concentration nanobubble water was prepared and its physicochemical properties were sensed to construct a standardized nanobubble water sample.

[0008] A multi-scale interface mass transfer modeling method was used to dynamically simulate the contact process between the nanobubble water sample and the Chinese medicinal materials, and multi-dimensional dissolution characteristic parameters were constructed.

[0009] A dissolution enhancement regulator is constructed, and the multi-objective collaborative optimization network in the regulator is used to perform parameter coupling processing on the multi-dimensional dissolution feature parameters, and the dissolution enhancement weight matrix is ​​output.

[0010] Based on the dissolution enhancement weight matrix, a multi-mechanism weighted dissolution objective function is constructed. The multi-path fusion dissolution results under different preparation processes are calculated, and the dissolution efficiency of active ingredients is predicted based on the dissolution results.

[0011] The extraction process of traditional Chinese medicine is optimized and controlled based on the predicted dissolution efficiency of the active ingredients.

[0012] Preferably, the process of preparing high-concentration nanobubble water and sensing its physicochemical properties to construct a standardized nanobubble water sample is as follows:

[0013] Nanobubble water is prepared using any one of the following methods: pressurized dissolution and depressurized release method, cascade method, or rotary evaporation method.

[0014] The particle size distribution, bubble concentration, zeta potential and dissolved oxygen content of the nanobubble water are collected simultaneously. Based on the data, a standardized nanobubble water sample is constructed, wherein the standardized nanobubble water sample includes bubble physical parameters and chemical activity indicators.

[0015] Preferably, the process of dynamically simulating the contact process between the nanobubble water sample and the traditional Chinese medicine using a multi-scale interface mass transfer modeling method to construct multi-dimensional dissolution characteristic parameters is as follows:

[0016] Micro-area flow field and concentration gradient modeling were performed on the interface between the nanobubble water sample and the medicinal material. Key features were extracted and dimensionless processing was performed to obtain a normalized interface mass transfer feature vector. The key features include surface tension change rate, local free radical generation rate and cell wall stress-strain response characteristics.

[0017] A multi-scale mass transfer coupling model based on stochastic differential equations is constructed. The model is used to perform dynamic evolution analysis on the normalized interface mass transfer characteristic vector and output multi-dimensional dissolution characteristic parameters.

[0018] Preferably, the process of constructing a multi-scale mass transfer coupling model based on stochastic differential equations, using the model to perform dynamic evolution analysis on the normalized interface mass transfer characteristic vector, and outputting multi-dimensional dissolution characteristic parameters is as follows:

[0019] Obtain the normalized interface mass transfer characteristics, input them into the multi-scale mass transfer coupling model, and obtain the model's hidden state variable output matrix;

[0020] Define the objective functional of the multi-scale mass transfer coupling model, and use the output matrix of the hidden state variables as the input of the objective functional to solve for the optimal mass transfer path weights.

[0021] By combining the hidden state variable output matrix and the optimal mass transfer path weights, multidimensional dissolution characteristic parameters are constructed.

[0022] Preferably, the process of constructing the dissolution enhancement regulator, and using a multi-objective collaborative optimization network in the regulator to perform parameter coupling processing on the multi-dimensional dissolution feature parameters, to output the dissolution enhancement weight matrix, is as follows:

[0023] Initialize the dissolution enhancement weight matrix based on the aforementioned multidimensional dissolution feature parameters;

[0024] A dissolution enhancement regulator is constructed using a multi-objective collaborative optimization network. The regulator and an adaptive particle swarm optimization algorithm are used to iteratively update the initial dissolution enhancement weight matrix, and the output is a function that maximizes the multi-objective comprehensive benefit.

[0025] The dissolution enhancement weight matrix corresponding to the maximization of the multi-objective comprehensive benefit function is used as the output result.

[0026] Preferably, the function for maximizing the multi-objective comprehensive benefit is specifically:

[0027]

[0028] Where Φ represents the multi-objective comprehensive benefit function, R i E represents the relative dissolution rate of the i-th active ingredient. i To correspond to energy consumption or time cost, α i With β i These represent the dissolution gain weight and the cost penalty coefficient, respectively, ω i The importance weight of the components.

[0029] Preferably, the process of constructing a multi-mechanism weighted dissolution objective function based on the dissolution enhancement weight matrix, calculating the multi-path fusion dissolution results under different preparation processes, and predicting the dissolution efficiency of the active ingredient based on the dissolution results is as follows:

[0030] A weighted dissolution response matrix is ​​constructed based on the dissolution enhancement weight matrix and the latent state variable output matrix.

[0031] Based on the weighted dissolution response matrix and the multi-objective comprehensive benefit function, a dissolution objective function based on multi-mechanism weighting is constructed, and the fusion dissolution response vector is calculated based on this function.

[0032] Based on the weighted dissolution response matrix and the fused dissolution response vector, the dissolution efficiency score for each process path is calculated.

[0033] The leaching efficiency score was fused and analyzed using the entropy weight-fuzzy comprehensive evaluation method to obtain the optimal leaching process recommendation result.

[0034] Preferably, the dissolution objective function based on multi-mechanism weighting is specifically:

[0035]

[0036] Where K is the total number of process paths, λ k The contribution coefficient to the mechanism of the k-th process; γ is the regularization parameter, and B is the fusion dissolution response vector. For the multi-mechanism weighted dissolution objective function value, W k H is the dissolution enhancement weight matrix corresponding to the k-th process. k For the output matrix corresponding to the hidden state variables, Y k This is the measured dissolution response vector, where ⊙ represents element-wise multiplication. This represents the Frobenius norm.

[0037] Preferably, the process of using the entropy weight-fuzzy comprehensive evaluation method to perform fusion analysis on the dissolution efficiency score to obtain the optimal dissolution process recommendation result is as follows:

[0038] The dissolution efficiency membership degrees of berberine, geniposide, and hesperidin under each process route were calculated, and a fuzzy evaluation matrix was constructed.

[0039] The objective weights of each component index are calculated based on the information entropy theory, and a comprehensive weight vector is formed by combining expert weighting.

[0040] The fuzzy evaluation matrix and the comprehensive weight vector are combined to obtain the comprehensive evaluation value of each process path;

[0041] The process route with the highest comprehensive evaluation value was selected as the optimal leaching process recommendation.

[0042] According to a second aspect of the present invention, a dissolution enhancement system for active ingredients of traditional Chinese medicine based on nanobubble Ganlan water is provided, comprising: a nanobubble water preparation and sensing module, a multi-scale mass transfer modeling module, a dissolution enhancement regulation module, a multi-pathway fusion dissolution analysis module, and a process optimization feedback control module;

[0043] The nanobubble water preparation and sensing module is used to prepare high-concentration nanobubble Ganlan water and to sense its physicochemical properties, thereby constructing a standardized nanobubble water sample.

[0044] The multi-scale mass transfer modeling module is used to dynamically simulate the contact process between nanobubble water samples and Chinese medicinal materials using a multi-scale interface mass transfer modeling method, and to construct multi-dimensional dissolution characteristic parameters.

[0045] The dissolution enhancement regulation module is used to construct a dissolution enhancement regulator. The regulator uses a multi-objective collaborative optimization network to perform parameter coupling processing on multi-dimensional dissolution feature parameters and outputs a dissolution enhancement weight matrix.

[0046] The multi-path fusion dissolution analysis module is used to construct a multi-mechanism weighted dissolution objective function based on the dissolution enhancement weight matrix, calculate the multi-path fusion dissolution results under different preparation processes, and predict the dissolution efficiency of active ingredients.

[0047] The process optimization feedback control module is used to dynamically adjust and optimize the extraction process parameters of traditional Chinese medicine based on the prediction results of the multi-path fusion dissolution analysis module.

[0048] Compared with the prior art, the present invention has the following technical effects:

[0049] This invention addresses the technical problems of low dissolution efficiency of active ingredients, uncontrollable processes, and lack of systematic integration of the physicochemical mechanisms of nanobubbles in existing traditional Chinese medicine extraction technologies by constructing highly stable, high-concentration nanobubble water as a green extraction medium and combining it with a multi-mechanism synergistic dissolution control strategy. The method and system ensure the repeatability, controllability, and high efficiency of nanobubble water in traditional Chinese medicine extraction, and are suitable for the extraction of medicinal slices containing typical active ingredients such as berberine, geniposide, and hesperidin, such as Coptis chinensis, Gardenia jasminoides, and Citrus reticulata peel, providing effective technical support for intelligent manufacturing of traditional Chinese medicine.

[0050] It should be understood that the description in the Summary of the Invention is not intended to limit the key or essential features of the embodiments of the present invention, nor is it intended to restrict the scope of the invention. Other features of the invention will become readily apparent from the following description. Attached Figure Description

[0051] The above and other features, advantages, and aspects of the various embodiments of the present invention will become more apparent from the accompanying drawings and the following detailed description. The drawings are provided for a better understanding of the invention and are not intended to limit the invention. In the drawings, the same or similar reference numerals denote the same or similar elements, wherein:

[0052] Figure 1 A schematic flowchart of a method for enhancing the dissolution of active ingredients of traditional Chinese medicine based on nanobubble Ganlan water according to an embodiment of the present invention is shown.

[0053] Figure 2 A schematic diagram of a system for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble Ganlan water, according to an embodiment of the present invention, is shown.

[0054] Figure 3This paper illustrates a linear diagram showing the change in nanobubble concentration with circulation in a gas pressure dissolution and depressurization release method according to an embodiment of a method for enhancing the dissolution of active ingredients of traditional Chinese medicine based on nanobubble-infused water according to an embodiment of the present invention.

[0055] Figure 4 This paper illustrates a schematic diagram showing the linear variation of nanobubble concentration with circulation in a water-drop method for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble-infused water, according to an embodiment of the present invention.

[0056] Figure 5 This illustration shows a schematic diagram illustrating the linear relationship between the concentration of nanobubbles and temperature in a rotary evaporation method for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble-based Ganlan water, according to an embodiment of the present invention. Detailed Implementation

[0057] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0058] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0059] like Figure 1 As shown, this embodiment provides a method for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble-infused water, including the following steps:

[0060] S101. Prepare high-concentration nanobubble water and perform physicochemical property sensing to construct a standardized nanobubble water sample.

[0061] First, this embodiment focuses on the preparation of high-concentration nanobubble water and the simultaneous sensing of its physicochemical properties to construct standardized nanobubble water samples. In this step, the pressurized dissolution-decompression release method is used as the main preparation method, specifically including: placing deionized water in a sealed pressure vessel, introducing high-purity oxygen or air under constant temperature conditions, allowing the gas to fully dissolve in the water at a pressure of 0.3 to 0.8 MPa for 15 to 45 minutes;

[0062] The pressure relief valve was then quickly opened, causing the system pressure to drop sharply to atmospheric pressure, thereby inducing the precipitation of supersaturated gas and the formation of nanoscale bubbles.

[0063] Alternative solutions include the drop system, which uses a multi-stage drop tower to repeatedly impact the water surface under gravity, generating nanobubbles through cavitation; or the rotary evaporation method, which uses a high-speed rotating liquid film to form microbubble nuclei in a low-pressure environment and stabilize them into nanobubbles.

[0064] During the preparation process, a physicochemical parameter sensing unit is simultaneously activated. This unit consists of a laser particle size analyzer, a nanoparticle tracking and analysis system (NTA), a zeta potential meter, and a dissolved oxygen sensor. The laser particle size analyzer is used to monitor the bubble size distribution in real time, ensuring that more than 90% of the bubble diameters are within the 50 to 200 nanometer range. The NTA system is used to accurately count the number of bubbles per unit volume, with a target concentration of not less than 1 × 10⁻⁶. 8 Bubble / mL; Zeta potential meter measures the surface potential of bubbles, requiring an absolute value greater than 30 mV to ensure colloidal stability; Dissolved oxygen sensor records dissolved oxygen content, with a typical range of 8 to 12 mg / L.

[0065] The above four types of data are aggregated by the data acquisition card and then normalized according to preset thresholds: the bubble particle size distribution is dimensionless with 100 nanometers as the reference, and the bubble concentration is normalized to 1×10⁻⁶. 8 The calibration was performed at 1 / mL, with a zeta potential referenced at -35 mV and dissolved oxygen at 10 mg / L. The calibrated dataset constituted a standardized nanobubble water sample, serving as the sole input medium for subsequent modeling and regulation.

[0066] S102. The contact process between the nanobubble water sample and the Chinese medicinal materials is dynamically simulated using a multi-scale interface mass transfer modeling method to construct multi-dimensional dissolution characteristic parameters.

[0067] Furthermore, this embodiment employs a multi-scale interface mass transfer modeling method to dynamically simulate the contact process between the standardized nanobubble water sample and the traditional Chinese medicine, in order to extract and process interface mass transfer-related features and output multi-dimensional dissolution characteristic parameters.

[0068] The modeling process begins with the construction of the micro-flow field at the solid-liquid interface. Typical Chinese medicinal materials, such as Coptis chinensis slices, are selected, with surface roughness Ra ranging from 5 to 15 micrometers and internal pore diameters distributed between 1 and 50 micrometers. The medicinal material slices are fixed within the reaction chamber of a microfluidic chip, and standardized nanobubbles of Ganlan water are injected. Simultaneously, a high-speed microscopic imaging system (frame rate no less than 10,000 fps) and a confocal Raman spectrometer are activated for in-situ monitoring. High-speed imaging captures the entire process of bubble adhesion, slippage, and collapse on the medicinal material surface, while Raman spectroscopy detects the characteristic peak of hydroxyl radicals (·OH) in the interfacial region in real time (wavenumber approximately 3600 cm⁻¹). -1 The intensity change of ).

[0069] Based on this, three key features were extracted: the surface tension change rate γ', defined as the derivative of the gas-liquid interfacial tension per unit time, obtained by inversion using the Young-Laplace equation; the local hydroxyl radical generation rate r·OH, derived from the Raman signal intensity through calibration curve conversion; and the stress-strain response feature ε(t) of the cell wall under bubble collapse impact, calculated from high-speed image sequences using digital image correlation (DIC) technology.

[0070] The above characteristics were dimensionless: γ' divided by the intrinsic surface tension coefficient of water, 72 mN / m, and r·OH divided by the baseline formation rate, 1×10⁻⁶. -9 The normalized interfacial mass transfer characteristic vector is formed by dividing mol / (L·s) and ε(t) by the strain threshold corresponding to the cell wall elastic modulus of 0.05. .

[0071] Based on this, a multi-scale mass transfer coupling model based on stochastic differential equations is constructed. This model uses time t, spatial coordinate x, and bubble dynamics parameters (such as radius R and oscillation frequency f) as independent variables, and the transmembrane diffusion flux of the active ingredient J and the cell wall rupture probability P as independent variables. b and interfacial adsorption equilibrium constant K a These are state variables. The core equations of the model are as follows:

[0072] (1)

[0073] (2)

[0074] (3)

[0075] Among them, D eff Where C is the effective diffusion coefficient, k1 to k5 are empirical rate constants, σ(t) is the instantaneous stress, and σt is the concentration field. c H is the critical fracture stress, H(·) is the Heaviside step function, and ξ1(t), ξ2(t), and ξ3(t) are Gaussian white noise terms that satisfy the Itô integral condition, used to characterize microscopic random disturbances.

[0076] The normalized interface mass transfer feature vector v is used as the initial excitation input to the model, and the hidden state variable output matrix is ​​generated through the hidden state variable update mechanism. , where T is the number of time steps and N is the dimension of the state variable.

[0077] Define the objective functional J of the model as the objective:

[0078] (4)

[0079] Among them, S trans(t) represents the interfacial mass transfer entropy yield, M cum (t) represents the cumulative dissolution mass, and η1 and η2 are weighting coefficients.

[0080] The optimal mass transfer path weights that minimize J are solved using the variational method. Finally, the hidden state variable output matrix H is combined with the optimal mass transfer path weights. Tensor product operations are performed to construct a structured multidimensional set of dissolution feature parameters Θ = {θ1, θ2, ..., θ}. L}, where each θ l These correspond to physical quantities such as mass transfer resistance coefficient, effective diffusion coefficient, and interfacial reaction rate constant.

[0081] S103. Construct a dissolution enhancement regulator, and use the multi-objective collaborative optimization network in the regulator to perform parameter coupling processing on the multi-dimensional dissolution feature parameters, and output the dissolution enhancement weight matrix.

[0082] Furthermore, in this embodiment, a dissolution enhancement regulator is constructed to perform parameter coupling processing on the multidimensional dissolution feature parameters in order to output a dissolution enhancement weight matrix.

[0083] The regulator initializes a weight matrix W0 of dimension M×Q, where M is the number of active ingredient types (e.g., berberine, geniposide, and hesperidin, a total of 3 types), and Q is the number of mass transfer mechanisms (e.g., diffusion-dominated, fragmentation-dominated, oxidation-assisted, etc., a total of 5 types). The core of the regulator is a Pareto front-based multi-objective collaborative optimization network, which consists of M parallel subnetworks. Each subnetwork corresponds to the dissolution optimization objective of one active ingredient, and the subnetworks achieve cross-component information exchange through shared hidden layers. The network input is a multi-dimensional dissolution feature parameter set Θ, and the output is the updated weight matrix W.

[0084] The adaptive particle swarm optimization (APSO) algorithm is used for iterative optimization of the network: each particle represents a candidate weight matrix, its position vector is the expansion of W, and its velocity vector is updated according to the standard PSO formula. However, the inertia weight ω and the learning factors c1 and c2 are dynamically adjusted according to the convergence degree of the current generation. The optimization objective is to maximize the multi-objective comprehensive benefit function Φ, which is expressed as:

[0085] (5)

[0086] Among them, R i The relative dissolution rate of the i-th active ingredient is defined as the ratio of the dissolution amount in the experimental group to the dissolution amount in the control group (ordinary water extraction); E i To correspond to energy consumption or time cost, expressed in kilowatt-hours or minutes; α i With β iThese are the dissolution gain weight and the cost penalty coefficient, respectively, pre-set by process economic analysis; ω i The importance weight of the ingredients is assigned according to the pharmacopoeia or clinical value.

[0087] The algorithm iterates until Φ changes less than 10 for 10 consecutive generations. -4 The corresponding weight matrix at this point is the final output dissolution enhancement weight matrix. .

[0088] S104. Based on the dissolution enhancement weight matrix, a multi-mechanism weighted dissolution objective function is constructed. The multi-path fusion dissolution results under different preparation processes are calculated respectively, and the dissolution efficiency of active ingredients is predicted based on the dissolution results.

[0089] Subsequently, this embodiment constructs a multi-mechanism weighted dissolution objective function based on the weight matrix and predicts the dissolution efficiency of each active ingredient.

[0090] Specifically, The weighted dissolution response matrix S is generated by performing an element-wise Hadamard product with the hidden state variable output matrix H from the multi-scale mass transfer model. ⊙ H. Combining this matrix with the measured dissolution response vector Y (obtained by high performance liquid chromatography-HPLC), a multi-mechanism weighted dissolution objective function L is constructed. fusion :

[0091] (6)

[0092] Where K represents the total number of process paths (e.g., three paths: pressure method, cascade method, and rotary evaporation method), λ k The mechanism contribution coefficient for the k-th process is determined by regression analysis of historical data; γ is the regularization parameter with a value of 0.01; B is the fusion dissolution response vector, determined by minimizing L... fusion The solution is obtained.

[0093] Based on S and B, the dissolution efficiency scores of the three active ingredients under each process route were calculated. The scoring method adopted was the entropy weight-fuzzy comprehensive evaluation method: First, the dissolution efficiency of each ingredient under each process was transformed by membership degree conversion, and a trapezoidal membership function was used to map the dissolution rate to the [0,1] interval, specifically:

[0094] (7)

[0095] Among them, [a i ,d i [μ] represents the effective interval for dissolution rate, from which a 3×3 fuzzy evaluation matrix U=[μ] is constructed. i,k ].

[0096] Secondly, calculate the information entropy of each component. To obtain objective weights Combined with expert weighting, a comprehensive weight vector is formed. Finally, through composition operation (Taking the maximum and minimum values ​​together), we obtain the comprehensive evaluation value s for each path. k1 s k2 s k3 The process path with the highest evaluation value is selected as the optimal leaching process recommendation.

[0097] S105. Optimize and implement feedback control of the traditional Chinese medicine extraction process based on the predicted dissolution efficiency of the active ingredients.

[0098] Finally, this embodiment implements dynamic adjustment and closed-loop feedback control of the extraction process parameters of traditional Chinese medicine based on the dissolution efficiency prediction results.

[0099] The optimal process recommendation is translated into specific process parameter instructions, including: if the gas pressure method is recommended, then the pressure is set to 0.6 MPa, the dissolution time to 30 minutes, and the bubble concentration to 1.2 × 10⁻⁶. 8 Extraction rate: 100 cells / mL; extraction temperature: 60℃; extraction time: 90 minutes; stirring speed: 200 rpm.

[0100] The aforementioned instructions are sent to the PLC controller via industrial Ethernet to drive the execution unit. During the extraction process, three key process variables are collected in real time: the residual amount of active ingredients in the medicinal residue (indirectly measured by an online near-infrared spectrometer), the turbidity of the extract (using a turbidimeter, unit NTU), and the pH value (using a glass electrode pH meter). The collected data are compared with preset target values ​​to calculate the deviation: the residual amount target is less than 10% of the initial content, the turbidity target is 50 to 150 NTU, and the pH target is 5.5 to 6.5. If any deviation exceeds the allowable threshold (e.g., residual amount deviation > 5%), a feedback adjustment mechanism is triggered: the current process data is sent back to the multi-scale mass transfer modeling module, the interface mass transfer feature vector is reinitialized, and a new round of modeling-control-analysis process is started to generate corrected process parameters, achieving closed-loop optimization control of the extraction process.

[0101] like Figure 2 As shown, this embodiment also provides a dissolution enhancement system for active ingredients of traditional Chinese medicine based on nanobubble Ganlan water, including: nanobubble water preparation and sensing module 1, multi-scale mass transfer modeling module 2, dissolution enhancement regulation module 3, multi-path fusion dissolution analysis module 4, and process optimization feedback control module 5.

[0102] The nanobubble water preparation and sensing module 1 is used to prepare high-concentration nanobubble water and sense its physicochemical properties, thereby constructing a standardized nanobubble water sample.

[0103] The multi-scale mass transfer modeling module 2 is used to dynamically simulate the contact process between nanobubble water samples and traditional Chinese medicine using a multi-scale interface mass transfer modeling method, and to construct multi-dimensional dissolution characteristic parameters.

[0104] The dissolution enhancement regulation module 3 is used to construct the dissolution enhancement regulator. The multi-objective collaborative optimization network in the regulator is used to perform parameter coupling processing on the multi-dimensional dissolution feature parameters, and the output is the dissolution enhancement weight matrix.

[0105] The multi-path fusion dissolution analysis module 4 is used to construct a multi-mechanism weighted dissolution objective function based on the dissolution enhancement weight matrix, calculate the multi-path fusion dissolution results under different preparation processes, and predict the dissolution efficiency of active ingredients;

[0106] The process optimization feedback control module 5 is used to dynamically adjust and optimize the extraction process parameters of traditional Chinese medicine based on the prediction results of the multi-path fusion dissolution analysis module 4.

[0107] Example

[0108] To verify the technical effects of the present invention, the following embodiments and comparative experiments were conducted.

[0109] In one specific embodiment, Coptis chinensis slices (batch number: HL20230501, containing ≥5.0% berberine) were selected as raw material and extracted using the method described in this invention. The specific steps are as follows: Nanobubble ganlan water was prepared using a pressurized dissolution-decompression release method at a pressure of 0.6 MPa for 30 min, resulting in bubbles with an average particle size of 120 nm and a concentration of 1.15 × 10⁻⁶. 8 The water was used to extract Coptis chinensis at 60℃ for 90 min with stirring at 200 rpm. The concentration of berberine was 92.3%, with a zeta potential of -38 mV and dissolved oxygen of 10.2 mg / L.

[0110] In this embodiment, during the preparation of nanobubble kanlan water using the pressurized dissolution-depressurized release method, the effects of pressure (0.15, 0.35, 0.55 MPa) and flow rate (10, 25, 40 mL / min) on the nanobubble concentration with the number of cycles (1, 5, 9, 13, 17, 21, 25, 29) were systematically investigated. Experimental data showed that the nanobubble concentration increased significantly with the number of cycles. For example, at a release pressure of 0.15 MPa and an air intake rate of 40 mL / min, the initial nanobubble concentration increased from 0 particles / mL to 6.3 × 10⁻⁶ particles / mL in one cycle. 6 After 29 cycles, the concentration range increased to 1.8 × 10⁻⁶ particles / mL. 7The experimental results show that the synergistic effect of release pressure and gas flow rate is key to regulating the concentration of nanobubbles. Data shows that a release pressure of 0.15 MPa and an inlet flow rate of 40 mL / min under 29 cycles resulted in a concentration of 1.8 × 10⁻⁶ particles / mL. 7 For particles / mL greater than 25 mL / min and further exceeding 10 mL / min under the same conditions, a higher gas flow rate is necessary to maintain a certain bubble concentration; however, at 0.55 MPa, the system's dependence on high gas flow rates decreases significantly. For example, at a release pressure of 0.55 MPa, increasing the inlet flow rate from 10 mL / min to 40 mL / min reduces the nanobubble concentration after 29 cycles from approximately 1.8 × 10⁻⁶. 7 The number of particles / mL decreased to 1.3 × 10⁻⁶. 7 Particles / mL. In summary, a pressure of 0.15 MPa combined with a flow rate of 40 mL / min and a pressure of 0.55 MPa combined with a flow rate of 10 mL / min, after 29 cycles, were confirmed as the optimal preparation process for this system, as detailed below. Figure 3 As shown.

[0111] In the comparative example, ordinary deionized water was used to extract the same batch of Coptis chinensis slices under the same temperature, time, and stirring conditions, and the berberine dissolution rate was 76.8%. In another comparative example, unstandardized nano-bubble water (with large fluctuations in bubble concentration and a zeta potential of only -20 mV) was used for extraction under the same process, and the berberine dissolution rate was 81.5%, with a batch-to-batch relative standard deviation (RSD) of 8.7%, while the RSD of the embodiment of this invention was only 2.1%. The specific results are shown in Table 1.

[0112]

[0113] Comparative Example 3 used the standardized nanobubble water of the present invention, but did not enable the dissolution enhancement regulator and multi-path fusion analysis, and only extracted according to fixed parameters, indicating that the regulation module made a significant contribution to the improvement of dissolution efficiency.

[0114] Furthermore, the method of this invention was applied to the extraction of gardenia and dried tangerine peel. For gardenia (containing ≥2.5% geniposide), nanobubble water (particle size 150 nm, concentration 1.05 × 10⁻⁶) was prepared using a cascading method. 8After process optimization according to this invention, the dissolution rate of geniposide reached 89.7%, which is 23.9% higher than that of ordinary water extraction (72.4%). Specifically, in this embodiment, the experimental results show that the number of cycles and the drop height are the two dominant factors affecting the concentration of nanobubbles. During 29 cycles, the concentration of nanobubbles showed a significant upward trend with the increase of the number of cycles and the drop height. This is mainly attributed to the conversion of greater drop potential energy into stronger liquid surface impact and shearing action, thereby effectively promoting air incorporation. Further analysis revealed a significant synergistic relationship between the drop height and the optimal flow rate: at a relatively low height of 30 cm, a flow rate of approximately 9.0 × 10⁻⁶ can be achieved. 6 The peak concentration of particles / mL was superior to other flow rates; however, at higher heights of 50 cm and 70 cm, the low flow rate (1 mL / s) showed better performance, with peak concentrations reaching approximately 2.1 × 10⁻⁶. 7 The particles / mL was significantly higher than 1.3 × 10⁻⁶ under high flow conditions at the same height. 7 Particles / mL. Furthermore, the enhancement effect brought about by increased height is also significant; under the same medium flow rate conditions, a concentration of 1.7 × 10⁻⁶ particles / mL was obtained at a height of 50 cm. 7 The particles / mL is much higher than 1.0 × 10 at a height of 30 cm. 6 The particles / mL. These phenomena indicate that under high impact kinetic energy conditions, excessive flow velocity, by shortening the effective shear time of the water or exacerbating bubble coalescence and escape, actually limits the stable enrichment of nanobubbles. In summary, the optimal process parameters for this experimental system were determined after 29 cycles at a drop height of 50 cm and a low flow rate of 1 mL / s, as detailed below. Figure 4 As shown.

[0115] For dried tangerine peel (containing ≥3.0% hesperidin), nano-bubble water (particle size 90 nm, concentration 1.3 × 10⁻⁶) was prepared using rotary evaporation. 8 The optimized hesperidin dissolution rate was 91.2%, a 21.4% increase compared to the control group (75.1%). Specifically, experiments demonstrated that the synergistic effect of negative pressure and heating significantly influenced the nanobubble generation efficiency. When the system temperature exceeded the saturated vapor pressure of water corresponding to the negative pressure, the nanobubble generation rate increased significantly, and its concentration showed an exponential growth trend with increasing temperature. Under a negative pressure of -0.08 MPa, the nanobubble concentration increased from 2.0 × 10⁻⁸ MPa at 30℃ to 91.2%. 6 The particles / mL increased to 3.5 × 10⁻⁶ at 80 °C. 7The concentration of particles / mL increased by nearly 17.5 times, highlighting the crucial role of temperature in the formation of nanobubbles. In contrast, the concentration in the atmospheric pressure control group remained below 5.0 × 10⁻⁶ particles / mL within the same temperature range. 6 The concentration of particles / mL and the absence of a significant temperature-sensitive effect further confirm the dominant role of the negative pressure environment in suppressing bubble collapse and promoting gas dissolution. In summary, treatment at -0.08 MPa and 80℃ for 30 minutes was identified as the optimal process for preparing high-concentration nanobubble water in this rotary evaporation system, as detailed below. Figure 5 As shown.

[0116] The comprehensive process evaluation values ​​of the three types of medicinal materials were all higher than 0.85 (out of 1.0), proving that the method has good universality.

[0117] It should be noted that, for the sake of simplicity, the foregoing method embodiments are all described as a series of actions. However, those skilled in the art should understand that the present invention is not limited to the described order of actions, because according to the present invention, some steps can be performed in other orders or simultaneously. Furthermore, those skilled in the art should also understand that the embodiments described in the specification are all optional embodiments, and the actions and modules involved are not necessarily essential to the present invention.

[0118] It should be understood that the various forms of processes shown above can be used to reorder, add, or delete steps. For example, the steps described in this invention can be executed in parallel, sequentially, or in different orders, as long as the desired result of the technical solution disclosed in this invention can be achieved, and this is not limited herein.

[0119] The specific embodiments described above do not constitute a limitation on the scope of protection of this invention. Those skilled in the art should understand that various modifications, combinations, sub-combinations, and substitutions can be made according to design requirements and other factors. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this invention should be included within the scope of protection of this invention.

Claims

1. A method for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble-infused water, characterized in that, Includes the following steps: High-concentration nanobubble water was prepared and its physicochemical properties were sensed to construct a standardized nanobubble water sample. A multi-scale interface mass transfer modeling method was used to dynamically simulate the contact process between the nanobubble water sample and the Chinese medicinal materials, and multi-dimensional dissolution characteristic parameters were constructed. A dissolution enhancement regulator is constructed, and the multi-objective collaborative optimization network in the regulator is used to perform parameter coupling processing on the multi-dimensional dissolution feature parameters, and the dissolution enhancement weight matrix is ​​output. Based on the dissolution enhancement weight matrix, a multi-mechanism weighted dissolution objective function is constructed. The multi-path fusion dissolution results under different preparation processes are calculated, and the dissolution efficiency of active ingredients is predicted based on the dissolution results. The extraction process of traditional Chinese medicine is optimized and controlled based on the predicted dissolution efficiency of the active ingredients.

2. The method for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble-infused water according to claim 1, characterized in that, The process of preparing high-concentration nanobubble water and sensing its physicochemical properties to construct a standardized nanobubble water sample is as follows: Nanobubble water is prepared using any one of the following methods: pressurized dissolution and depressurized release method, cascade method, or rotary evaporation method. The particle size distribution, bubble concentration, zeta potential and dissolved oxygen content of the nanobubble water are collected simultaneously. Based on the data, a standardized nanobubble water sample is constructed, wherein the standardized nanobubble water sample includes bubble physical parameters and chemical activity indicators.

3. The method for enhancing the dissolution of active ingredients of traditional Chinese medicine based on nanobubble-infused water according to claim 1, characterized in that, The process of dynamically simulating the contact process between the nanobubble water sample and the traditional Chinese medicine using a multi-scale interface mass transfer modeling method, and constructing multi-dimensional dissolution characteristic parameters, is as follows: Micro-area flow field and concentration gradient modeling were performed on the interface between the nanobubble water sample and the medicinal material. Key features were extracted and dimensionless processing was performed to obtain a normalized interface mass transfer feature vector. The key features include surface tension change rate, local free radical generation rate and cell wall stress-strain response characteristics. A multi-scale mass transfer coupling model based on stochastic differential equations is constructed. The model is used to perform dynamic evolution analysis on the normalized interface mass transfer characteristic vector and output multi-dimensional dissolution characteristic parameters.

4. The method for enhancing the dissolution of active ingredients of traditional Chinese medicine based on nanobubble-infused water according to claim 3, characterized in that, The process of constructing a multi-scale mass transfer coupling model based on stochastic differential equations, using the model to perform dynamic evolution analysis on the normalized interface mass transfer characteristic vector, and outputting multi-dimensional dissolution characteristic parameters is as follows: Obtain the normalized interface mass transfer characteristics, input them into the multi-scale mass transfer coupling model, and obtain the model's hidden state variable output matrix; Define the objective functional of the multi-scale mass transfer coupling model, and use the output matrix of the hidden state variables as the input of the objective functional to solve for the optimal mass transfer path weights. By combining the hidden state variable output matrix and the optimal mass transfer path weights, multidimensional dissolution characteristic parameters are constructed.

5. The method for enhancing the dissolution of active ingredients of traditional Chinese medicine based on nanobubble-infused water according to claim 1, characterized in that, The process of constructing a dissolution enhancement regulator, and using a multi-objective collaborative optimization network in the regulator to perform parameter coupling processing on the multi-dimensional dissolution feature parameters, to output the dissolution enhancement weight matrix, is as follows: Initialize the dissolution enhancement weight matrix based on the aforementioned multidimensional dissolution feature parameters; A dissolution enhancement regulator is constructed using a multi-objective collaborative optimization network. The regulator and an adaptive particle swarm optimization algorithm are used to iteratively update the initial dissolution enhancement weight matrix, and the output is a function that maximizes the multi-objective comprehensive benefit. The dissolution enhancement weight matrix corresponding to the maximization of the multi-objective comprehensive benefit function is used as the output result.

6. The method for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble-infused water according to claim 5, characterized in that, The function for maximizing the multi-objective comprehensive benefit is specifically as follows: ； Where Φ represents the multi-objective comprehensive benefit function, R i E represents the relative dissolution rate of the i-th active ingredient. i To correspond to energy consumption or time cost, α i With β i These represent the dissolution gain weight and the cost penalty coefficient, respectively, ω i The importance weight of the components.

7. The method for enhancing the dissolution of active ingredients of traditional Chinese medicine based on nanobubble-infused water according to claim 1, characterized in that, The process of constructing a multi-mechanism weighted dissolution objective function based on the dissolution enhancement weight matrix, calculating the multi-path fusion dissolution results under different preparation processes, and predicting the dissolution efficiency of active ingredients based on the dissolution results is as follows: A weighted dissolution response matrix is ​​constructed based on the dissolution enhancement weight matrix and the latent state variable output matrix. Based on the weighted dissolution response matrix and the multi-objective comprehensive benefit function, a dissolution objective function based on multi-mechanism weighting is constructed, and the fusion dissolution response vector is calculated based on this function. Based on the weighted dissolution response matrix and the fused dissolution response vector, the dissolution efficiency score for each process path is calculated. The leaching efficiency score was fused and analyzed using the entropy weight-fuzzy comprehensive evaluation method to obtain the optimal leaching process recommendation result.

8. The method for enhancing the dissolution of active ingredients of traditional Chinese medicine based on nanobubble-infused water according to claim 7, characterized in that, The dissolution objective function based on multi-mechanism weighting is specifically as follows: ； Where K is the total number of process paths, λ k The contribution coefficient to the mechanism of the k-th process; γ is the regularization parameter, and B is the fusion dissolution response vector. For the multi-mechanism weighted dissolution objective function value, W k H is the dissolution enhancement weight matrix corresponding to the k-th process. k For the output matrix corresponding to the hidden state variables, Y k This is the measured dissolution response vector, where ⊙ represents element-wise multiplication. This represents the Frobenius norm.

9. The method for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble-infused water according to claim 7, characterized in that, The process of using the entropy weight-fuzzy comprehensive evaluation method to perform fusion analysis on the dissolution efficiency score and obtain the optimal dissolution process recommendation result is as follows: The dissolution efficiency membership degrees of berberine, geniposide, and hesperidin under each process route were calculated, and a fuzzy evaluation matrix was constructed. The objective weights of each component index are calculated based on the information entropy theory, and a comprehensive weight vector is formed by combining expert weighting. The fuzzy evaluation matrix and the comprehensive weight vector are combined to obtain the comprehensive evaluation value of each process path; The process route with the highest comprehensive evaluation value was selected as the optimal leaching process recommendation.

10. A system for enhancing the dissolution of active ingredients in traditional Chinese medicine based on nanobubble-infused water, used to implement the method as described in any one of claims 1-9, characterized in that, include: The module includes a nanobubble water preparation and sensing module (1), a multi-scale mass transfer modeling module (2), a dissolution enhancement and regulation module (3), a multi-path fusion dissolution analysis module (4), and a process optimization feedback control module (5). The nanobubble water preparation and sensing module (1) is used to prepare high-concentration nanobubble Ganlan water and to sense its physicochemical properties, thereby constructing a standardized nanobubble water sample. The multi-scale mass transfer modeling module (2) is used to dynamically simulate the contact process between nanobubble water samples and Chinese medicinal materials using the multi-scale interface mass transfer modeling method, and to construct multi-dimensional dissolution characteristic parameters. The dissolution enhancement regulation module (3) is used to construct a dissolution enhancement regulator. The multi-objective collaborative optimization network in the regulator is used to perform parameter coupling processing on the multi-dimensional dissolution feature parameters, and the output is the dissolution enhancement weight matrix. The multi-path fusion dissolution analysis module (4) is used to construct a multi-mechanism weighted dissolution objective function based on the dissolution enhancement weight matrix, calculate the multi-path fusion dissolution results under different preparation processes, and predict the dissolution efficiency of active ingredients. The process optimization feedback control module (5) is used to dynamically adjust and optimize the extraction process parameters of traditional Chinese medicine based on the prediction results of the multi-path fusion dissolution analysis module (4).

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