Preparation method of aloe medicinal preparation for treating phlebitis

Abstract

This invention relates to the field of physicochemical improvement of traditional Chinese medicine preparations, and discloses a method for preparing an aloe vera traditional Chinese medicine preparation for treating phlebitis. The method includes: linearly heating an aloe vera concentrate to expose the polysaccharide components in a bindable state; uniformly adding a saturated stock solution of Glauber's salt to induce the polysaccharide components to curl in a specific direction using dissociated ions, thereby constructing a hybrid microdomain with three-dimensional micro-grid channels in situ to obtain a drug-loaded matrix; adding a liquid eutectic phase and ultrafine powder of traditional Chinese medicine, and using the rebound stress generated by linear cooling to achieve physical anchoring. This invention induces macromolecular conformational recombination through ionic templates, transforming electrolytes into crosslinking points that maintain the strength of the backbone, effectively avoiding the risk of crystallization in high-salt systems. Combined with the osmotic pressure pumping force generated by the hybrid microdomains, it drives the active components to penetrate deep into the tissue, achieving a synergistic improvement in preparation stability and transdermal throughput.

Description

Technical Field

[0001] This invention belongs to the field of physical and chemical improvement technology of traditional Chinese medicine preparations, and particularly relates to a method for preparing an aloe vera traditional Chinese medicine preparation for treating phlebitis. Background Technology

[0002] Currently, in clinical nursing procedures, phlebitis induced by chemical irritation and mechanical friction is a common complication affecting infusion safety and patient prognosis. Topical preparations alleviate local inflammation by constructing a physical intervention layer on the skin surface of the affected area. Aloe polysaccharides, as a natural polymer material, are commonly used as drug-carrying matrices in such preparations. To generate an osmotic pressure gradient sufficient to drive the absorption of local edema fluid, these preparations often contain a high proportion of strong electrolyte components. Existing technologies mostly focus on the physicochemical screening and ratio optimization of matrix components. Even with changes in matrix types, the lack of intervention in the microscopic preparation logic of the system makes it difficult to resolve the contradiction between drug release and stability. For example, the authorization announcement number CN1086... Chinese invention patent 71120B discloses a compound aloe vera emulsion and its preparation method. It constructs a drug delivery system through multi-component emulsification technology and uses oil components to improve skin permeability. Such preparations belong to the macroscopic physical blending of components and lack the directional guidance of a polymer matrix at the molecular chain segment level. When facing a high osmotic pressure electrolyte environment, due to the lack of structural locking of ion movement and controlled adjustment of polysaccharide chain conformation, it is easy to induce the peeling and disordered collapse of the hydration layer of polysaccharide chain segments, resulting in salting out, crystallization and viscosity fluctuations in the system, reducing the physical stability of the preparation. In addition, the lack of microscopic mass transfer channels limits the penetration efficiency of active components into the deep tissue, making it difficult to achieve both high osmotic pressure driving force and transdermal flux.

[0003] However, in systems involving natural polysaccharides and strong electrolytes, high ionic strength generates a charge shielding effect, stripping the hydration layer of the polysaccharide molecular chains and triggering salting out. This process induces conformational collapse of the gel matrix, leading to a decrease in system viscosity, component stratification, and solute crystallization. Conventional methods maintain physical equilibrium by increasing the amount of synthetic thickener or reducing the concentration of the active ingredient. However, excessive physical thickening creates a diffusion barrier within the matrix, hindering the migration of active ingredients such as peony bark and safflower to deeper subcutaneous tissues. Simultaneously, inorganic salt ions generate disordered crystal nucleation during solvent evaporation, resulting in hard microcrystals that reduce drug bioavailability and cause mechanical damage to the inflamed skin.

[0004] Therefore, the technical problem to be solved by this invention is how to construct a formulation system with physical stability and directional mass transfer characteristics while maintaining the osmotic pressure driving force. Summary of the Invention

[0005] The present invention aims to solve the problem that it is difficult to balance the stability and osmotic pressure driving force of topical Chinese medicine preparations under high ionic strength due to matrix collapse and solute crystallization.

[0006] In this technical solution, a method for preparing an aloe vera traditional Chinese medicine preparation for treating phlebitis includes the following steps: Step S101: Aloe vera concentrate is put into a reaction vessel with a variable temperature jacket. Under stirring at a speed of 100 r / min to 200 r / min, it is heated to 42°C to 46°C at a linear heating rate of 1.5°C / min to 2.5°C / min. The heat energy is used to weaken the hydrogen bonds between polysaccharide molecular chains in aloe vera concentrate, so that the polysaccharide components are in a binding state with fully exposed polar sites on the side chains, thus obtaining a matrix pre-activated system. Step S102: Prepare a saturated stock solution of Glauber's salt with a mass fraction of 25% to 32%. Add the saturated stock solution dropwise to the matrix pre-activation system at a rate of 1 g / min to 3 g / min using a metering pump. Use the sodium ions and sulfate ions dissociated from the saturated stock solution as structure-inducing templates to cause the polysaccharide components to undergo conformational evolution from disordered expansion to directional coiling around the ion axis. In situ, an ion-polysaccharide hybrid microdomain with a three-dimensional micro-grid pore structure is formed inside the matrix pre-activation system to obtain a drug-loaded matrix with predetermined rheological properties. In step S103, the cooling rate of the drug-loaded matrix is ​​adjusted to 0.5℃ / min to 1.5℃ / min. When the temperature drops to the range of 30℃ to 35℃, a liquid eutectic phase formed by physically mixing borneol and peppermint in a mass ratio of 1:3 to 1:1, and a composite ultrafine powder of peony bark, safflower, Panax notoginseng, and Salvia miltiorrhiza are added sequentially to the drug-loaded matrix. The homogenization speed is controlled at 3000 r / min to 5000 r / min for 30 min to 50 min. Finally, the system is cooled back to room temperature at a cooling rate of 0.8℃ / min to 1.2℃ / min. The one-dimensional inward rebound stress generated by the three-dimensional micro-grid pores during the cooling process is used to physically anchor the liquid eutectic phase and the ultrafine powder inside the three-dimensional micro-grid pores, thus obtaining an aloe vera traditional Chinese medicine preparation for treating phlebitis.

[0007] Preferably, in step S102, by controlling the injection rate of the saturated stock solution, the charge density distribution of the ion-polysaccharide hybrid microdomains in the matrix pre-activation system decreases from the center to the surrounding area. The physical barrier formed by the three-dimensional microgrid channels locks in the electrolyte ions, so that the formulation does not precipitate crystals in an environment of 4°C to 45°C.

[0008] Preferably, in step S103, the liquid eutectic phase is wrapped around the outer surface of the three-dimensional microgrid channels. When the preparation comes into contact with the human skin surface, the osmotic pressure difference between the high concentration of ions inside the three-dimensional microgrid channels and the external skin tissue generates a pumping force, which actively drives the active ingredients of the composite Chinese medicine ultrafine powder to penetrate across the stratum corneum.

[0009] Preferably, in step S103, the average particle size of the composite Chinese medicine ultrafine powder is 10μm to 30μm. The ultrafine powder is anchored in the grid gaps between the three-dimensional micro-grid channels by utilizing the physical cavities generated by the mutual stacking of ion-polysaccharide hybrid micro-domains. The adhesion strength of the preparation on the skin surface of the affected area is maintained by the frictional force of the multiphase interface.

[0010] Preferably, step S101 further includes the step of: adjusting the circumferential speed of the impeller blades in the reactor, and applying shear mechanical force to the polysaccharide component in conjunction with the linear heating rate, to help break the hydrogen bonds within the polysaccharide molecules, increase the flexibility of the polysaccharide chain segments, and provide the kinetic premise for the steric hindrance transformation of the subsequent ion-induced coiling process.

[0011] Preferably, step S102 further includes the step of: maintaining the real-time equilibrium temperature of the system inside the reactor at a constant 42°C, and completing the injection process of the saturated reserve liquid under this thermal equilibrium state, so as to ensure that when the polysaccharide components are oriented to curl around the ion axis, the thermal motion energy level of the molecular chain is maintained in the preset steady-state energy range.

[0012] Preferably, step S103 further includes the step of: when the drug-loaded matrix is ​​cooled to 35°C and the dynamic viscosity of the system reaches the range of 2000 mPa·s to 3000 mPa·s, adding ultrafine powder, and using the physical suspension buoyancy generated by the increase in the viscosity of the drug-loaded matrix to counteract the aggregation or sedimentation of the ultrafine powder caused by gravity.

[0013] Preferably, after step S103 is completed, the prepared material is filled into a sealed container and placed in a constant temperature environment of 4°C for 24 hours to age. The low temperature treatment further stabilizes the microscopic three-dimensional mesh morphology of the ion-polysaccharide hybrid microdomain and releases the internal residual stress generated in the stirring and integration stage of the formulation, thereby improving the physical stability of the finished product.

[0014] Preferably, throughout the entire process from step S101 to step S103, the pH value of the entire system is controlled to be stable between 5.5 and 6.5 by adding a pH adjuster. The charge compensation effect generated by acid-base balance is used to prevent the dissociation or collapse of the three-dimensional micro-lattice channels caused by the repulsion of like charges between polysaccharide components and ions.

[0015] Compared with existing technologies, the method for preparing aloe vera traditional Chinese medicine preparations for treating phlebitis in this invention has the following advantages: 1. In the preparation of aloe vera traditional Chinese medicine preparations, by using the electrolyte ions generated by the dissociation of Glauber's salt as a structural template, the acetylated polysaccharide chains of aloe vera are induced to curl in a directional manner around the ion axis, and an ion-polysaccharide hybrid microdomain with three-dimensional spatial confinement is constructed in situ within the system. This mechanism converts chemical energy into physical confinement energy of a stable matrix, which restricts the disordered migration and nucleation growth of inorganic salt ions from a physical perspective, effectively avoiding the risk of salting out and crystallization of high-concentration electrolytes in complex systems, maintaining the physical stability of the preparation during wide temperature variation cycling, and eliminating the mechanical damage to the affected skin caused by hard particles generated by disordered crystallization in traditional ointments.

[0016] 2. The liquid eutectic phase formed by borneol and peppermint in a specific ratio serves as the continuous phase of the system, reducing the degree of orderly accumulation of lipids in the stratum corneum of the skin. Combined with the reconstructed charged polysaccharide micropores, when the formulation comes into contact with the affected skin, the internal pressure caused by the ion gradient generates a pumping effect, actively driving active components such as paeonol and safflower yellow pigment to penetrate into the deep tissues of the skin. This kinetic support based on the microscopic topological network enables the formulation to have a strong transmembrane flux, improving the deep penetration ability of the drug without the use of chemical penetration enhancers and shortening the onset time of local edema reduction.

[0017] 3. The composite Chinese herbal medicine ultrafine powder is anchored in the gaps of the grid constructed by the eutectic matrix and aloe polysaccharides through the steric hindrance effect, forming a stable multiphase distribution system. This structure effectively locks in volatile components, prevents the escape of active ingredients, and causes the polysaccharide molecular chains to be oriented and arranged on the skin surface during the coating process, forming a flexible drug film. Its specific rheological properties give the formulation excellent spreadability and adhesion. While ensuring the permeability of skin tissue, it enhances the absorption efficiency of the formulation for local inflammatory exudate, and achieves a synergistic effect between the physical stability and permeability of the formulation. Attached Figure Description

[0018] Figure 1 This is a schematic diagram illustrating the entire process of preparing aloe vera traditional Chinese medicine preparations and the principle of in-situ construction of microstructures. Figure 2 This is a diagram of the multi-dimensional control logic and skin interface mass transfer architecture of the entire preparation process of this invention. Detailed Implementation

[0019] The technical solutions of the embodiments of this application will be clearly described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of this application are within the scope of protection of this application.

[0020] It should be noted that all directional and positional terms used in this invention, such as: up, down, left, right, front, back, vertical, horizontal, inner, outer, top, bottom, transverse, longitudinal, center, etc., are only used to explain the relative positional relationship and connection between components in a specific state (as shown in the accompanying drawings). They are only for the convenience of describing this invention and do not require that this invention be constructed and operated in a specific orientation. Therefore, they should not be construed as limiting this invention. In addition, the descriptions of "first," "second," etc., in this invention are for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated.

[0021] In the description of this invention, unless otherwise explicitly specified and limited, the terms installation, connection, and linking should be interpreted broadly. For example, they can refer to fixed connections, detachable connections, or integral connections; they can refer to mechanical connections; they can refer to direct connections or indirect connections through an intermediate medium; they can refer to the internal connection of two components. For those skilled in the art, the specific meaning of the above terms in this invention can be understood according to the specific circumstances.

[0022] In the description of this specification, references to the terms "an embodiment," "some embodiments," "illustrative embodiments," "examples," "specific examples," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example, and the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0023] A method for preparing an aloe vera-based traditional Chinese medicine preparation for treating phlebitis includes the following steps: Step S101: Aloe vera concentrate is put into a reaction vessel with a variable temperature jacket. Under stirring at a speed of 100 r / min to 200 r / min, it is heated to 42°C to 46°C at a linear heating rate of 1.5°C / min to 2.5°C / min. The heat energy is used to weaken the hydrogen bonds between polysaccharide molecular chains in aloe vera concentrate, so that the polysaccharide components are in a binding state with fully exposed polar sites on the side chains, thus obtaining a matrix pre-activated system. Step S102: Prepare a saturated stock solution of Glauber's salt with a mass fraction of 25% to 32%. Add the saturated stock solution dropwise to the matrix pre-activation system at a rate of 1 g / min to 3 g / min using a metering pump. Use the sodium ions and sulfate ions dissociated from the saturated stock solution as structure-inducing templates to cause the polysaccharide components to undergo conformational evolution from disordered expansion to directional coiling around the ion axis. In situ, an ion-polysaccharide hybrid microdomain with a three-dimensional micro-grid pore structure is formed inside the matrix pre-activation system to obtain a drug-loaded matrix with predetermined rheological properties. In step S103, the cooling rate of the drug-loaded matrix is ​​adjusted to 0.5℃ / min to 1.5℃ / min. When the temperature drops to the range of 30℃ to 35℃, a liquid eutectic phase formed by physically mixing borneol and peppermint in a mass ratio of 1:3 to 1:1, and a composite ultrafine powder of peony bark, safflower, Panax notoginseng, and Salvia miltiorrhiza are added sequentially to the drug-loaded matrix. The homogenization speed is controlled at 3000 r / min to 5000 r / min for 30 min to 50 min. Finally, the system is cooled back to room temperature at a cooling rate of 0.8℃ / min to 1.2℃ / min. The one-dimensional inward rebound stress generated by the three-dimensional micro-grid pores during the cooling process is used to physically anchor the liquid eutectic phase and the ultrafine powder inside the three-dimensional micro-grid pores, thus obtaining an aloe vera traditional Chinese medicine preparation for treating phlebitis.

[0024] Preferably, in step S102, by controlling the injection rate of the saturated stock solution, the charge density distribution of the ion-polysaccharide hybrid microdomains in the matrix pre-activation system decreases from the center to the surrounding area. The physical barrier formed by the three-dimensional microgrid channels locks in the electrolyte ions, so that the formulation does not precipitate crystals in an environment of 4°C to 45°C.

[0025] Preferably, in step S103, the liquid eutectic phase is wrapped around the outer surface of the three-dimensional microgrid channels. When the preparation comes into contact with the human skin surface, the osmotic pressure difference between the high concentration of ions inside the three-dimensional microgrid channels and the external skin tissue generates a pumping force, which actively drives the active ingredients of the composite Chinese medicine ultrafine powder to penetrate across the stratum corneum.

[0026] Preferably, in step S103, the average particle size of the composite Chinese medicine ultrafine powder is 10μm to 30μm. The ultrafine powder is anchored in the grid gaps between the three-dimensional micro-grid channels by utilizing the physical cavities generated by the mutual stacking of ion-polysaccharide hybrid micro-domains. The adhesion strength of the preparation on the skin surface of the affected area is maintained by the frictional force of the multiphase interface.

[0027] Preferably, step S101 further includes the step of: adjusting the circumferential speed of the impeller blades in the reactor, and applying shear mechanical force to the polysaccharide component in conjunction with the linear heating rate, to help break the hydrogen bonds within the polysaccharide molecules, increase the flexibility of the polysaccharide chain segments, and provide the kinetic premise for the steric hindrance transformation of the subsequent ion-induced coiling process.

[0028] Preferably, step S102 further includes the step of: maintaining the real-time equilibrium temperature of the system inside the reactor at a constant 42°C, and completing the injection process of the saturated reserve liquid under this thermal equilibrium state, so as to ensure that when the polysaccharide components are oriented to curl around the ion axis, the thermal motion energy level of the molecular chain is maintained in the preset steady-state energy range.

[0029] Preferably, step S103 further includes the step of: when the drug-loaded matrix is ​​cooled to 35°C and the dynamic viscosity of the system reaches the range of 2000 mPa·s to 3000 mPa·s, adding ultrafine powder, and using the physical suspension buoyancy generated by the increase in the viscosity of the drug-loaded matrix to counteract the aggregation or sedimentation of the ultrafine powder caused by gravity.

[0030] Preferably, after step S103 is completed, the prepared material is filled into a sealed container and placed in a constant temperature environment of 4°C for 24 hours to age. The low temperature treatment further stabilizes the microscopic three-dimensional mesh morphology of the ion-polysaccharide hybrid microdomain and releases the internal residual stress generated in the stirring and integration stage of the formulation, thereby improving the physical stability of the finished product.

[0031] Preferably, throughout the entire process from step S101 to step S103, the pH value of the entire system is controlled to be stable between 5.5 and 6.5 by adding a pH adjuster. The charge compensation effect generated by acid-base balance is used to prevent the dissociation or collapse of the three-dimensional micro-lattice channels caused by the repulsion of like charges between polysaccharide components and ions.

[0032] Example 1: In the application scenario of mechanical phlebitis and local skin barrier damage caused by high-dose infusion of hypertonic drugs in the intensive care unit, when hospitalized patients are continuously infused with 20% mannitol solution or high-concentration potassium chloride solution, the blood vessel wall is chemically stimulated and infiltrates, resulting in increased local tissue pressure and subcutaneous drug leakage damage. Conventional topical preparations, due to the high ionic strength of Glauber's salt component, undergo hard recrystallization on the damaged skin surface as the solvent evaporates, not only puncture the skin barrier, but also cause conformational collapse of the traditional gel matrix under the salting-out effect, trapping the active ingredient within the disordered physical barrier, making it difficult to generate sufficient permeation flux.

[0033] Aloe vera concentrate was placed in a reaction vessel equipped with a temperature-controlled jacket. Under stirring at 100-200 rpm, the temperature was increased to 42-46°C at a linear heating rate of 1.5-2.5°C / min. This thermal energy weakened the hydrogen bonds between the polysaccharide molecular chains, exposing the polar sites of the side chains. A 25-32% (w / w) saturated sodium sulfate stock solution was then added dropwise to the matrix pre-activation system at a rate of 1-3 g / min using a metering pump. The dissociated sodium and sulfate ions served as structural induction templates. The induced polysaccharide components evolve from disordered expansion to directional coiling around the ion axis, forming in situ ion-polysaccharide hybrid microdomains with a three-dimensional micro-lattice structure within the matrix pre-activated system. Under the thermodynamic principle of the colloidal interface, the charge gradient and ion-induced process rely on specific flow field shear constraints to avoid bulk salting out. A saturated electrolyte solution is added dropwise under mechanical stirring at 150 r / min, forcibly dispersing into discrete droplets with an average diameter of 50 μm to 80 μm. Under this forced dispersion state, due to the matrix pre-activated system having an apparent viscosity exceeding 1500 mPa·s, the viscous resistance is slow. The diffusion rate of strong electrolyte ions from the discrete droplets to the surrounding polysaccharide continuous phase was impeded. This localized mass transfer restriction effect caused each isolated microdroplet phase to form a transient concentration field within its 50μm to 80μm microscopic spatial scale. This field exhibited a rapid, parabolic decay towards the solid-liquid interface, with the droplet core as the concentration extreme point. This allowed for the successful construction of a charge density gradient distribution decreasing from the center outwards within the microscopic domain, without violating the macroscopic strong stirring and homogenization trend of the reactor. This provided an energy bias basis for subsequent in-situ crosslinking, with polysaccharide molecular segments only affected at the solid-liquid interface of the discrete droplets. Local high-concentration ion double-layer compression effect drives in-situ crosslinking, monomer crosslinking generates micro-lattice channels with nanoscale pore size. During the cooling integration stage, a large number of independent micro-region crosslinking nodes collide, stack, and fuse to construct a three-dimensional continuous grid skeleton containing physical holes ranging from 15μm to 40μm. Ultrafine powders with an average particle size of 10μm to 30μm are trapped in the cavity network formed by the spatial steric hindrance effect generated by phase mixing, and do not directly penetrate into the nanoscale micro-lattice channels. By converting chemical energy into physical constraint energy of a stable matrix, the contradiction between high ion strength and physical stability is resolved at the structural level.

[0034] The cooling rate of the drug-loaded matrix was adjusted from 0.5℃ / min to 1.5℃ / min. When the temperature dropped to the range of 30℃ to 35℃, a liquid eutectic phase formed by physically mixing borneol and peppermint at a mass ratio of 1:3 to 1:1, and composite traditional Chinese medicine ultrafine powder with an average particle size of 10μm to 30μm were added sequentially to the drug-loaded matrix. The homogenization speed was controlled at 3000r / min to 5000r / min for 30min to 50min, and finally the homogenization speed was adjusted from 0.8℃ / min to 1.2℃ / min. The cooling rate at in allows the system to return to room temperature. Utilizing the one-dimensional inward rebound stress generated by the three-dimensional micro-grid pores during cooling, the liquid eutectic phase and ultrafine powder are physically anchored within the three-dimensional micro-grid pores. The liquid eutectic phase alters the ordered structure of the skin's lipid layer, and this, combined with the osmotic pressure pumping force generated by the high concentration of ions within the three-dimensional micro-grid pores, drives the active ingredients of the composite traditional Chinese medicine ultrafine powder to penetrate deep into the tissue. The reason why the inward rebound stress exhibits one-dimensional geometric characteristics is that the polysaccharide molecular chains are arranged around... The uniaxially oriented rod-shaped electrolyte ion clusters are directionally coiled. When the system temperature decreases linearly across the glass transition boundary of the polysaccharide chain segment, the main chain backbone arranged along the ion axis remains absolutely dimensionally locked due to rigid steric hindrance. Only the vertically extended flexible side chains undergo radial contraction driven by water loss and cooling. This asymmetric annealing process of the microstructure based on molecular orientation anisotropy manifests as a one-dimensional normal contraction force pointing absolutely towards the normal direction of the pore center on the three-dimensional pore wall, thus creating a directional compression and physical embedding of the powder inside the pores like a mechanical gripper. Because the formulation induces the construction of an ordered topological network through ion templates, no particle damage caused by disordered crystallization is observed at the contact site, and the ratio of the storage modulus to the loss modulus of the formulation is maintained at 1.2 to 1.5, forming a flexible drug film with repair capabilities on the damaged skin surface. By adding a pH adjuster to stabilize the pH value of the system at 5.5 to 6.5, the charge compensation effect generated by acid-base balance is used to maintain the stability of the three-dimensional micro-grid pores, shortening the local swelling subsidence cycle and increasing the penetration efficiency index. It is within the preset high-throughput range. The calculation formula is as follows: ;in, The penetration efficiency index. The surface tension coefficient of the formulation is taken as 48 mN / m in this embodiment. The dynamic viscosity of the eutectic is 0.15 Pa·s in this embodiment.

[0035] Example 2: The current verification method dynamically regulates the permeation flux and physical stability under different inflammatory infiltration intensities. The experimental platform uses a Franz diffusion cell system to simulate the permeation environment of human skin. The receiving cell has constant temperature circulation control capability with a temperature control accuracy of 0.2℃ and is equipped with an automatic liquid level compensation sensor with a sampling frequency of 10Hz. The data source is isolated porcine back skin as the permeation barrier. The experimental design includes four sample groups. The sample group of this invention uses the preparation prepared in Example 1; the control sample group 1 is a preparation prepared by conventional physical blending and has the same component types as the sample group of this invention; the control sample group 2 is a partially missing control group, in which no Glauber's salt component is added during the preparation process; the control sample group 3 is an out-of-range control group, in which the injection rate of the Glauber's salt saturated stock solution is set to 5g / min, which exceeds the limited range of 1g / min to 3g / min.

[0036] In the drug-loaded matrix preparation stage, the injection rate The setting depends on the matching degree between the relaxation time constant of the polysaccharide chain segments and the shear rate of the system. The engineering contradiction it balances lies in the constraint between the risk of instantaneous salting out induced by high ionic strength and the degree of orderliness in the construction of micropores. If the injection rate... The value tends towards the lower limit of the range, allowing sufficient time for chain segment rearrangement, which helps improve the regularity of the three-dimensional micro-lattice channels, thereby maintaining osmotic pressure balance when faced with high concentrations of inflammatory exudate. For simulating severe phlebitis conditions, the injection rate is selected... Using 1.5 g / min as an engineering example, the experimental procedure set an initial baseline by adding a 20% mannitol solution to the skin surface to simulate the hypertonic state of tissue fluid caused by inflammation. The formulations of each group were then applied to the skin surface, and the storage modulus within the drug-loaded matrix was monitored using a rheometer. The storage modulus of the sample group of the present invention after the addition of saturated sodium sulfate stock solution varies. The energy modulus of control group 3 increased from an initial 125 Pa to 458 Pa and remained stable. After experiencing sharp fluctuations, the pressure dropped to 85 Pa, indicating that the high injection rate triggered irreversible matrix salting-out collapse, making it impossible to form effective three-dimensional microgrid channels.

[0037] In the value closed-loop verification phase, the permeability index is calculated by measuring the concentration of the effective component in the receiving cell. Experimental data show that, in a simulated inflammatory environment, the permeability index of the sample group of this invention is [missing information]. The permeability index of control group 1 reached 3.25 mm / s. The osmotic pressure pump suction force of control group 2, which lacks Glauber's salt, is 1.12 mm / s, and its osmotic efficiency index is... The permeability of the sample group in this invention is 0.45 mm / s. It is not a simple summation of the functions of each component, but rather an enhancement of mass transfer efficiency through the physical constraint energy generated by the ion-polysaccharide hybrid microdomain. To verify the gradient of the technical effect, three levels of inflammation severity variables—low, medium, and high—were set, corresponding to simulated exudate concentrations of 5%, 10%, and 20%, respectively. The experimental results show that as the severity of inflammation increases, the permeability index of the sample group in this invention increases. The controlled linear growth trends were observed, reaching 1.25 mm / s, 2.18 mm / s, and 3.25 mm / s, respectively. When the inflammatory markers exceeded the preset threshold, the pH value inside the formulation was adjusted from 5.8 to 6.2. The stability of the three-dimensional microgrid channels was maintained through the charge compensation effect, thereby improving the permeability index. In the high-throughput range, The calculation formula is as follows: ,in, The penetration efficiency index. The surface tension coefficient of the formulation is 48.5 mN / m, which was measured in this experiment. The dynamic viscosity of the eutectic is 0.148 Pa, which was measured in this experiment. After completing the algebraic extraction of the pure physical rheological and surface tension parameters, to eliminate the dimensional difference between the original macroscopic physical dimensions of the parameter product and the microscopic transmembrane flux rate, the system calculation model incorporates a tissue structure relaxation transition constant based on in vitro tissue mass transfer calibration for divisor correction calibration. This constant has dimensions of kilograms squared per cubic meter second cubed. By algebraically dividing the result of the product with the variables, the dimensional distortion caused by the interaction of fluid resistance and interfacial tension in porous media is eliminated, ensuring that the final output evaluation index Ep meets the requirements. The dimensional standard form of Westerly osmosis law, expressed in mm / s, accurately expresses the actual permeation rate potential of active ingredients within a unified mathematical and physical context. The results of this experiment confirm that the preparation method of this invention, through asymmetric interference of the microscopic morphology of materials by the process sequence, forms a flexible drug film with repair capabilities on the surface of damaged skin. The ratio of storage modulus to loss modulus of the formulation remains at a stable level of 1.35. The ordered topological network constructed by ion template avoids the crystallization risk of high-salt systems, achieving a synergistic improvement in formulation stability and transdermal flux.

[0038] Example 3: This example combines Figures 1 to 2 The preparation method of an aloe vera traditional Chinese medicine preparation for treating phlebitis is described, such as... Figure 1As shown, aloe vera concentrate is added to step S101, and the hydrogen bonds between polysaccharide molecular chains are weakened by linear heating and mechanical stirring to fully expose the polar sites of the side chains. The resulting pre-activated matrix system is then introduced into step S102 and subjected to induced conformational evolution and uniform dropwise addition with the input Glauber's salt saturated stock solution. This causes the polysaccharide components to be oriented and curled around the ion axis and form a three-dimensional micro-lattice pore structure in situ to obtain a drug-loaded matrix with predetermined rheological properties. Finally, in step S103, a liquid eutectic phase and composite traditional Chinese medicine ultrafine powder are added sequentially, and the resulting one-dimensional inward rebound stress is used to achieve physical anchoring through cooling and homogenization treatment, ultimately obtaining an aloe vera traditional Chinese medicine preparation for treating phlebitis.

[0039] like Figure 2 As shown, this logical architecture encompasses five core nodes: control of hydrogen bond weakening in polysaccharide molecular chains, induction of directional coiling of polysaccharide components, in-situ construction of three-dimensional micro-lattice channels, inward rebound anchoring of active components, and regulation of acid-base balance and charge compensation. Among them, the in-situ construction of three-dimensional micro-lattice channels and the inward rebound anchoring of active components correspond to the aging and stabilization stage of micro-mesh morphology through logical pointing relationships. At the same time, the osmotic pressure pumping effect generated by the inward rebound anchoring of active components ensures that the active ingredients can effectively act on the skin tissue interface, realizing a logical closed loop from microstructure to macro-function of the formulation.

[0040] Example 4: In the production scenario of preparing aloe vera traditional Chinese medicine preparations with high permeability flux, when aloe vera concentrate undergoes matrix activation treatment in a reactor, if the linear heating rate exceeds the set range, the polysaccharide molecular chains will undergo disordered breakage, resulting in the matrix skeleton strength being lower than the predetermined standard. Conversely, if the heating rate is lower than the set range, it will trigger polysaccharide chain rearrangement, preventing subsequent ionic templates from inducing the formation of three-dimensional micro-lattice channels at effective polar sites. The aloe vera concentrate is added to a reactor equipped with a temperature-controlled jacket. This reactor has a mechanical stirring device with a rotation speed of 100 r / min to 200 r / min. The initial ambient temperature is set to 25°C, and the mixture is stirred at 150 r / min. The temperature was increased to 44℃ at a linear heating rate of 2.0℃ / min. During this temperature change, the hydrogen bonds between the aloe polysaccharide molecular chains were broken by thermal energy. A 28% sodium sulfate saturated stock solution was added dropwise to the matrix pre-activation system at a rate of 2 g / min using a metering pump. The electrostatic induction force generated by the solvation layer formed around the potential center of the polysaccharide side chain by the dissociated sodium and sulfate ions drove the polysaccharide components to directionally curl around the ion axis. An ion-polysaccharide hybrid microdomain with a three-dimensional micro-lattice pore structure was formed in situ inside the matrix pre-activation system, converting chemical potential energy into physical constraint energy to maintain the topological structure of the system, and suppressing matrix salting out caused by high ionic strength at the molecular level.

[0041] By controlling the linear heating rate to expose the ordered sites of polysaccharide segments, the topological network generated inside the system maintains the integrity of its spatial structure under homogeneous shear stress of 3000 r / min to 5000 r / min. When the temperature is lowered to 32℃, a liquid eutectic phase and composite traditional Chinese medicine ultrafine powder are added, with 5% citric acid solution added as a... Regulator, to the system The value was adjusted to 6.0, at which point the system's... The absolute value of the potential is 28.5 mV, which falls within the stable range of 25 mV to 35 mV. The charge compensation effect maintains the stability of the three-dimensional micro-lattice channels, preventing channel merging or collapse, and improving the adhesion of the formulation to the damaged skin surface and the penetration efficiency of the active ingredients. The precise locking of this stable potential range is based on the unique isoelectric point response mechanism of the aloe polysaccharide skeleton. According to rheological electrochemical testing, the isoelectric point of the polysaccharide polymer in this formulation system is between pH 3.2 and 3.5. When citric acid solution acts as a proton donor to precisely clamp the pH of the continuous phase at a weakly acidic baseline of 6.0, it induces the carboxyl functional groups of the polysaccharide side chains to maintain a specific proportion of partial dissociation. The released appropriate amount of free negative charge and the sodium ions fixed on the pore wall form a controlled-thickness electric double layer. Under thermodynamic equilibrium, the effective shear surface potential of the particle surface is limited within this specific energy threshold. The resulting formulation was tested under simulated mechanical phlebitis conditions, and the penetration efficiency index was measured. It is 2.95 mm / s. The calculation formula is as follows: ,in, The penetration efficiency index. The surface tension coefficient of the formulation is 49.2 mN / m, as measured in this example. The dynamic viscosity of the eutectic is 0.155 Pa, which was measured in this embodiment. Based on Darcy's law, which states that the fluid flux in porous media is inversely proportional to the fluid dynamic viscosity, the exponential... This is used solely for quantifying the initial physical state of the electrostatic binding energy within the system. When the formulation is applied to the skin surface of the affected area, free salts from external sweat and exudate penetrate into the matrix, breaking the existing charge shielding balance of the ion-polysaccharide hybrid microdomains. This triggers anisotropic swelling of the three-dimensional continuous mesh, opening local channels and activating transmembrane flux. The evaluation model calculates the following relationship: ,in, The concentration gradient generates an osmotic pressure difference, which constitutes a positive driving force for mass migration. The real-time dynamic viscosity of the liquid eutectic phase at the skin physiological interface temperature of 37°C constitutes the fluid resistance term. To predetermine the dimensionless coefficient of the cuticle mass transfer impedance, the calculation path establishes a quantitative mapping of the physical interface hydrodynamic boundary of the micro-network drug release behavior. The formulation prepared based on thermodynamic control and potential energy balance exhibits a stable three-dimensional topological network structure in a high-salt environment, providing a physical channel with high mass transfer efficiency for the effective components of the composite traditional Chinese medicine ultrafine powder.

[0042] Example 5: In the process of adapting the preparation process for aloe vera concentrate raw materials from different origins and harvesting seasons, due to the physical differences in the initial degree of polymerization of aloe polysaccharides from different batches, the apparent viscosity of the aloe vera concentrate was measured using a rotational viscometer at a constant temperature of 25°C before the preparation process started. According to the measurements Numerical determination of the temperature rise equilibrium time during the substrate preheating stage This ensures that the degree of weakening of hydrogen bonds between polysaccharide molecular chains reaches a uniform standard; when the apparent viscosity of the obtained aloe vera concentrate is measured... 1500mPa Set the temperature rise equilibrium time at time s. For 15 minutes, if the apparent viscosity Increased to 2000 mPa s, then the temperature rise equilibrium time. Extending the time to 22 minutes, the matrix pre-activation system was in a standardized conformational distribution state before entering the ion implantation stage.

[0043] In the process of adding saturated sodium sulfate stock solution to the reactor using a precision delivery pump, to counteract the resistance to instantaneous flow rate caused by the increase in system viscosity, the back pressure of the pipeline, collected in real time by a pressure sensor, is used. Adjust the drive frequency of the delivery pump To increase the injection rate The driving frequency was stabilized within the preset range of 1 g / min to 3 g / min. With pipeline back pressure The linear compensation relationship between them is calculated using the following formula: ;in, For the drive frequency of the delivery pump, This is the flow compensation coefficient. This is the measured value of the pipeline back pressure. As the initial reference frequency, based on the Bernoulli equation's mapping relationship between fluid pressure drop and resistance, the flow compensation coefficient... Numerical extraction relies on a pre-system online calibration procedure. The calibration process involves measuring and recording the actual driving frequency required for the saturated Glauber's salt stock solution to reach a target throughput of 2 g / min at back pressure nodes of 15 kPa, 25 kPa, and 35 kPa before the matrix pre-activation system is introduced into the reactor. The least squares method is used to perform linear fitting on the collected pressure and frequency discrete data points, and the slope of the fitted line is directly assigned as the batch material flow compensation coefficient. The closed-loop calibration step transforms the batch-fluctuating hardware resistance constant into a definite computational input. The dissociated sodium and sulfate ions enter the reaction field at a constant flux, inducing the polysaccharide components to generate three-dimensional micro-grid channels with uniform pore size distribution. During continuous 24-hour stability monitoring, the spatial occupancy deviation rate of the three-dimensional topological network of the prepared formulation is below 0.5%, and the system is in a stable equilibrium state without crystallization.

[0044] Example 6: During the engineering calibration and structural verification of the microscopic topological network of the drug-loaded matrix, the local shear force distribution was affected by the volume amplification effect of the industrial reactor. During the preparation process, an online laser particle size analyzer was used to monitor the average effective diameter of the ion-polysaccharide hybrid microdomains. And use this as a feedback value for the stirring speed, setting the initial stirring speed to be... If obtained through real-time monitoring For sizes larger than 8 μm, the stirring speed is increased in increments of 10 r / min to increase the mechanical shear energy density, causing the three-dimensional micro-lattice channels to evolve towards the predetermined size until... Entering the 2μm to 5μm range, the osmotic pressure pumping force generated by Glauber's salt is matched with the diffusion flux of the active ingredients in the ultrafine powder of the compound Chinese medicine.

[0045] In the environmental temperature fluctuation compensation process of anchoring composite traditional Chinese medicine ultrafine powders through linear cooling, the linear shrinkage coefficient of the drug-loaded matrix is ​​used as a basis. Temperature difference with cooling Calculate structural locking strain The calculation formula is as follows: ;in, To lock the strain in the structure, The linear shrinkage coefficient of the drug-loaded matrix is ​​given. To reduce the temperature difference, when the calculated When the value reaches 0.012, the inward rebound stress experienced by the liquid eutectic phase and the composite Chinese medicine ultrafine powder inside the three-dimensional micro-grid channels causes the active components to be physically interlocked. The adhesion index of the prepared formulation on the surface of damaged skin remains above 0.85, and the release curve of the active ingredients of the composite Chinese medicine ultrafine powder conforms to the preset penetration flux model.

[0046] In the boundary verification of the physical loading stability and component compatibility of the formulation, since the average particle size of the composite traditional Chinese medicine ultrafine powder is between 10 μm and 30 μm, in order to ensure that the spatial distribution of solid particles in the ion-polysaccharide hybrid microdomain does not disrupt the topological continuity of the three-dimensional micro-lattice channels, the dispersion uniformity index of the powder in the matrix is ​​calibrated by centrifugal sedimentation. The homogenization speed is set to 4000 r / min. If the processing time... If the time is less than 30 minutes, the dispersion uniformity index is observed. The concentration is less than 0.75 and accompanied by powder agglomeration, which increases with processing time. Extend to 45 min, dispersion uniformity index The concentration was increased and stabilized at around 0.92. At this point, the solid ultrafine powder particles were completely coated at the cross-linking nodes of the three-dimensional micro-lattice channels, achieving a stable dispersion of the active component within the matrix. In the engineering procedure aimed at determining the optimal working window for the mixing ratio of the liquid eutectic phase and the drug-loaded matrix, based on the variation trend of the mass ratio of the liquid eutectic phase between 1:3 and 1:1, the storage modulus recovery rate of the system during the cooling rebound process was measured using a dynamic thermomechanical analyzer. If the amount of liquid eutectic phase added exceeds 8% of the drug-loaded matrix mass, the one-dimensional inward rebound stress generated by the three-dimensional micro-lattice channels will be attenuated due to excessive plasticization, leading to... To reduce the concentration to below 65%, the energy storage modulus recovery rate is achieved by controlling the addition amount within the range of 4% to 6% and coordinating with a final cooling rate of 0.8℃ / min to 1.2℃ / min. Maintaining a high level of over 88%, the physical anchoring force experienced by the compound Chinese medicine ultrafine powder during the cooling process reaches 12mN to 18mN, thereby achieving orderly release control of active ingredients while ensuring the physical strength of the formulation.

[0047] Example 7: Clinically Applicable Upgraded Formulation and End Product Validation. This invention demonstrates the compatibility of the preparation method with the upgraded clinical high-throughput formulation, resulting in a patch product directly applicable to clinical use. This invention simulates and deeply upgrades traditional Chinese medicine plastering therapy, utilizing a three-dimensional micro-grid channel constructed from fresh aloe vera concentrate as a drug carrier, achieving a technological leap from macroscopic infiltration to microscopic targeted penetration in traditional plastering. In the specific preparation process, steps S101 to S102 involve preparing the drug-loaded matrix according to the aforementioned standardized process. In step S103, the drug-loaded matrix is ​​prepared from peony bark, safflower, and... Based on the basic blood-activating components of Glauber's salt, borneol, and peppermint, Panax notoginseng and Salvia miltiorrhiza, which have stronger blood-activating and pain-relieving effects, are specially compounded to form a compound Chinese medicine dynamic system. Specifically, the ultrafine powder of Chinese medicine is adjusted to be a compound powder made by fully mixing Paeonia suffruticosa, Carthamus tinctorius, Panax notoginseng, and Salvia miltiorrhiza in a weight ratio of 2:2:1:1. Among them, Panax notoginseng is processed by ultrafine and ultra-low temperature pulverization process, and the average particle size is controlled at 15μm. When the drug-loaded matrix is ​​cooled to 32℃, the compound powder and the liquid eutectic phase are put into the reaction vessel and homogenized at a speed of 4500r / min for 45min.

[0048] The final material was filled into a medical hydrogel substrate to form a clinical topical hydrogel patch. In a simulated application scenario for severe phlebitis with significant local edema and induration, this upgraded patch showed significantly better clinical compliance than the traditional smear method. From a microscopic pharmacological mechanism analysis, the total saponins of Panax notoginseng and tanshinone components can form hydrogen bond-induced molecular-level adsorption with the micropore walls of aloe polysaccharides. Thus, without adding chemical penetration enhancers, the active ingredients are driven to penetrate the stratum corneum and directly act on the deep inflamed vascular walls by utilizing the osmotic pump effect of ions. Due to the introduction of Panax notoginseng and tanshinone... The potent blood-activating components of ginseng, combined with the sustained-release protection of aloe polysaccharides through three-dimensional pores, extend the effective action time of the drug components on the skin surface from the traditional 4 hours to more than 12 hours. Observation results show that the time for the skin temperature of the affected area to return to normal is shortened by 40%, significantly improving the clinical onset speed. Moreover, no mechanical damage or allergic reaction caused by Glauber's salt crystallization occurs on the skin surface. Experiments have shown that the addition of Panax notoginseng and Salvia miltiorrhiza not only does not destroy the physical stability of the original matrix, but also enhances the film-forming adhesion of the preparation through interaction with polysaccharide segments, achieving a high degree of synergy between clinical efficacy and preparation stability.

[0049] The embodiments of this application have been described above with reference to the accompanying drawings. Unless otherwise specified, the embodiments and features in the embodiments of this application can be combined with each other. This application is not limited to the specific implementation methods described above. The specific implementation methods described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of this application without departing from the scope of protection of this application, and all of them are within the protection scope of this application.

Claims

1. A method for preparing an aloe traditional Chinese medicine preparation for treating phlebitis, characterized in that, Includes the following steps: Step S101: Aloe vera concentrate is put into a reaction vessel with a variable temperature jacket. Under stirring at a speed of 100 r / min to 200 r / min, it is heated to 42°C to 46°C at a linear heating rate of 1.5°C / min to 2.5°C / min. The heat energy is used to weaken the hydrogen bonds between polysaccharide molecular chains in aloe vera concentrate, so that the polysaccharide components are in a binding state with fully exposed polar sites on the side chains, thus obtaining a matrix pre-activated system. Step S102: Prepare a saturated stock solution of Glauber's salt with a mass fraction of 25% to 32%. Add the saturated stock solution dropwise to the matrix pre-activation system at a rate of 1 g / min to 3 g / min using a metering pump. Use the sodium ions and sulfate ions dissociated from the saturated stock solution as structure-inducing templates to cause the polysaccharide components to undergo conformational evolution from disordered expansion to directional coiling around the ion axis. In situ, an ion-polysaccharide hybrid microdomain with a three-dimensional micro-grid pore structure is formed inside the matrix pre-activation system to obtain a drug-loaded matrix with predetermined rheological properties. In step S103, the cooling rate of the drug-loaded matrix is ​​adjusted to 0.5℃ / min to 1.5℃ / min. When the temperature drops to the range of 30℃ to 35℃, a liquid eutectic phase formed by physically mixing borneol and peppermint in a mass ratio of 1:3 to 1:1, and a composite ultrafine powder of peony bark, safflower, Panax notoginseng, and Salvia miltiorrhiza are added sequentially to the drug-loaded matrix. The homogenization speed is controlled at 3000 r / min to 5000 r / min for 30 min to 50 min. Finally, the system is cooled back to room temperature at a cooling rate of 0.8℃ / min to 1.2℃ / min. The one-dimensional inward rebound stress generated by the three-dimensional micro-grid pores during the cooling process is used to physically anchor the liquid eutectic phase and the ultrafine powder inside the three-dimensional micro-grid pores, thus obtaining an aloe vera traditional Chinese medicine preparation for treating phlebitis.

2. The method for preparing the aloe medicinal preparation for treating phlebitis according to claim 1, characterized in that, In step S102, by adjusting the injection rate of the saturated stock solution, the charge density distribution of the ion-polysaccharide hybrid microdomains in the matrix pre-activation system decreases from the center to the surrounding area. The physical barrier formed by the three-dimensional microgrid channels locks in the electrolyte ions, so that the formulation does not precipitate crystals in an environment of 4°C to 45°C.

3. The method for preparing an aloe vera traditional Chinese medicine preparation for treating phlebitis according to claim 1, characterized in that, In step S103, the liquid eutectic phase is wrapped around the outer surface of the three-dimensional micro-grid channels. When the preparation comes into contact with the human skin surface, the osmotic pressure difference between the high concentration of ions inside the three-dimensional micro-grid channels and the external skin tissue generates a pumping force, which actively drives the active ingredients of the composite Chinese medicine ultrafine powder to penetrate across the stratum corneum.

4. The method for preparing an aloe vera traditional Chinese medicine preparation for treating phlebitis according to claim 1, characterized in that, In step S103, the average particle size of the composite Chinese medicine ultrafine powder is 10μm to 30μm. The ultrafine powder is anchored in the grid gaps between the three-dimensional micro-grid channels by utilizing the physical cavities generated by the mutual stacking of ion-polysaccharide hybrid micro-domains. The adhesion strength of the preparation on the skin surface of the affected area is maintained by the frictional force of the multiphase interface.

5. The method for preparing an aloe vera traditional Chinese medicine preparation for treating phlebitis according to claim 1, characterized in that, Step S101 also includes the following steps: adjusting the circumferential speed of the impeller blades in the reactor, and applying shear mechanical force to the polysaccharide component in conjunction with the linear heating rate, to help break the hydrogen bonds within the polysaccharide molecules, increase the flexibility of the polysaccharide chain segments, and provide the kinetic premise for the steric hindrance transformation of the subsequent ion-induced coiling process.

6. The method for preparing an aloe vera traditional Chinese medicine preparation for treating phlebitis according to claim 1, characterized in that, Step S102 also includes the following steps: maintaining the real-time equilibrium temperature of the system inside the reactor at a constant 42°C, and completing the injection process of the saturated reserve liquid under this thermal equilibrium state to ensure that when the polysaccharide components are oriented and coiled around the ion axis, the thermal motion energy level of the molecular chain is maintained in the preset steady-state energy range.

7. The method for preparing an aloe vera traditional Chinese medicine preparation for treating phlebitis according to claim 1, characterized in that, Step S103 further includes the following steps: when the drug-loaded matrix is ​​cooled to 35°C and the dynamic viscosity of the system reaches the range of 2000 mPa·s to 3000 mPa·s, ultrafine powder is added, and the physical suspension buoyancy generated by the increase in the viscosity of the drug-loaded matrix is ​​used to counteract the aggregation or sedimentation of the ultrafine powder caused by gravity.

8. The method for preparing an aloe vera traditional Chinese medicine preparation for treating phlebitis according to claim 1, characterized in that, After step S103 is completed, the prepared material is filled into a sealed container and placed in a constant temperature environment of 4℃ for static aging for 24 hours. The low temperature treatment further stabilizes the microscopic three-dimensional mesh morphology of the ion-polysaccharide hybrid microdomain and releases the internal residual stress generated in the stirring and integration stage of the formulation, thereby improving the physical stability of the finished product.

9. A method for preparing an aloe vera traditional Chinese medicine preparation for treating phlebitis according to claim 1, characterized in that, Throughout the entire process from step S101 to step S103, the pH value of the entire system is stabilized between 5.5 and 6.5 by adding a pH adjuster. The charge compensation effect generated by acid-base balance is used to prevent the dissociation or collapse of the three-dimensional micro-lattice channels caused by the repulsion of like charges between polysaccharide components and ions.

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