Oral liquid clarification, settling stabilization and layering prevention preparation process

Abstract

The invention is applicable to the field of oral liquid preparation, and provides an oral liquid clarification, sedimentation stabilization and layering prevention preparation process which comprises the following steps: raw material pretreatment, gradient membrane separation, sedimentation stabilization system construction, mixing and homogenizing, online monitoring and regulation and finished product filling. According to the invention, through the design of the three-stage series gradient filtering membrane assembly, accurate layered interception of impurities with different particle sizes is realized, and the defect that a single-aperture filtering membrane is either incomplete in interception or easy to block is avoided; meanwhile, the pressure regulation and control module is used for dynamically adapting the filtering pressure of each stage of filtering membrane, and the smaller the membrane aperture is, the larger the corresponding filtering pressure is, so that each stage of membrane works in the optimal pressure interval, the low filtering efficiency caused by insufficient pressure is avoided, and the membrane damage or effective component interception caused by overhigh pressure is prevented; the stability of the clarification effect is remarkably improved, the cleanliness of the finally obtained clarified extracting solution is high, and the risk of impurity aggregation and precipitation in the subsequent storage process is greatly reduced.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of oral liquid preparation, and particularly relates to a preparation process for oral liquid that is clear, stable, precipitated and anti-layered. BACKGROUND

[0002] As a common dosage form, oral liquid has the advantages of convenient taking and rapid absorption, and is widely used in the fields of medicines, health products, etc. However, during the preparation and storage of oral liquid, the problems of clarity, stable precipitation and anti-layering have existed for a long time, and the existing technology has many deficiencies, which are embodied in the following aspects:

[0003] The effect of clarification filtration is poor, and the impurity interception is not complete: the existing oral liquid preparation mostly uses a single pore size filter membrane for clarification treatment, which cannot achieve accurate interception of impurities of different particle sizes; on the one hand, if the pore size of the filter membrane is too large, the fine impurities cannot be intercepted, and the residual impurities are easy to aggregate and form a precipitate during storage; on the other hand, if the pore size of the filter membrane is too small, it is easy to cause membrane clogging, reduce the filtration efficiency, and may also intercept the effective components in the oral liquid, affecting the curative effect of the product; in addition, the filtration pressure in the existing filtration process is mostly a fixed value, which cannot be dynamically adapted according to the membrane pore size and the characteristics of the raw materials, further leading to unstable clarification effect;

[0004] Poor adaptability of stable precipitation system and insufficient stability: in the existing technology, the selection and addition amount of the stable precipitation agent are mostly determined based on experience, and no precise adaptation relationship with the characteristics of the raw material components of the oral liquid is established; due to the differences in the raw material composition, density, viscosity, etc. of different oral liquids, the fixed stable precipitation system cannot meet the stable precipitation needs of various oral liquids; in some processes, a single stable precipitation agent is used, which is difficult to comprehensively improve the stability of the system, leading to the phenomenon of stratification, precipitation, etc. of the oral liquid during storage, which seriously affects the appearance and quality stability of the product and shortens the shelf life of the product;

[0005] Lack of real-time monitoring and control mechanism, poor product uniformity: the existing oral liquid preparation process is mostly open-loop operation, and after the key steps such as filtration, homogenization and stable precipitation agent addition, there is no real-time monitoring of the key indicators of the product (such as turbidity, particle size distribution, zeta potential); when the process parameters fluctuate, it cannot be adjusted in time, leading to differences in the quality of the oral liquid products of different batches or even the same batch; at the same time, there is no effective transmission linkage structure between the preparation equipment, which cannot realize continuous operation, and there are more human intervention links, further increasing the risk of product quality fluctuation;

[0006] Low process continuity limits production efficiency: In the existing process, each step is operated independently, and the transfer of raw materials between equipment relies on manual transfer or simple conveying devices, without forming a complete transmission and linkage closed loop. This not only leads to low production efficiency, but may also affect product quality due to pollution or environmental impact during the transfer of raw materials. In addition, the processing efficiency of each step is mismatched, which easily leads to problems with the smooth connection of processes, thus restricting the realization of large-scale production.

[0007] Therefore, a clarification, sedimentation stabilization, and anti-stratification preparation process for oral liquids is needed to solve the above problems. Summary of the Invention

[0008] The purpose of this invention is to provide a preparation process for clarifying, stabilizing, and preventing stratification of oral liquids to solve the problems mentioned in the background art.

[0009] To achieve the above objectives, the present invention provides the following technical solution:

[0010] The preparation process for clarifying, stabilizing, and preventing stratification of oral liquids includes the following steps:

[0011] S1. Raw material pretreatment: After crushing and extracting the raw materials for oral liquid, large particulate impurities are removed by primary filtration to obtain primary extract.

[0012] S2. Gradient membrane separation: The primary extract is filtered step by step through gradient filtration membrane modules with different pore sizes to obtain a clarified extract;

[0013] S3. Construction of the stabilizing system: Based on the component characteristics of the clarified extract, a suitable stabilizing agent component is added to it, and the mixture is stirred to obtain a mixture containing the stabilizing system.

[0014] S4. Mixing and homogenization: The mixture containing the stable sedimentation system is sent to a homogenizing device for high-pressure homogenization to improve the uniformity of the system.

[0015] S5. Online monitoring and control: The online monitoring module detects the turbidity, particle size distribution and zeta potential of the mixture in real time. Based on the detection results, the control module performs closed-loop control of the homogenization pressure and the amount of stabilizing agent added.

[0016] S6. Finished product filling: The mixed liquid that meets the requirements after adjustment is sterilized and then filled to obtain the oral liquid finished product.

[0017] In a further technical solution, in step S2, the gradient filtration membrane assembly adopts a three-stage series structure, and the pore size of each stage of the filtration membrane meets the requirements. ,in The pore size of the first-stage filter membrane. The pore size of the second-stage filter membrane. The pore size is for the third-stage filtration membrane;

[0018] To achieve precise stratification and retention of impurities of different particle sizes, pore size control follows the formula: Where n=1,2 (corresponding to the aperture change from the first level to the second level, and from the second level to the third level). Let n be the pore size of the nth stage filter membrane. denoted as pore size of the (n+1)th stage filter membrane, and k is the pore size reduction coefficient, ranging from 0.3 to 0.6. Its value can be flexibly adjusted according to the particle size distribution of impurities in the raw material. When the impurity distribution is wide, a smaller value (0.3 to 0.4) is used to ensure sufficient interception, and when the distribution is concentrated, a larger value (0.5 to 0.6) is used to improve filtration efficiency.

[0019] In a further technical solution, in step S2, the filtration pressure of the gradient filtration membrane module is dynamically adjusted by a pressure control module, and the adaptation relationship between the filtration pressure and the membrane pore size follows the formula: Where n=1,2,3 (corresponding to three-stage filtration membranes). The filtration pressure of the nth stage filtration membrane. As the reference pressure, The pore size of the first-stage filter membrane. Let be the pore size of the nth stage filter membrane.

[0020] In a further technical solution, in step S3, the adaptable settling agent component is a composite settling system, including a suspending agent, a thickener, and a surfactant, and the addition amount of each component follows the formula: ;in, Let i be the amount of the i-th type of stabilizing agent added. To clarify the quality of the extract, the overall scale of the addition amount is determined as a basic parameter; The baseline addition ratio for the i-th type of stabilizing agent is a basic ratio determined by a large number of experiments, which ensures the stabilizing effect. The formula for calculating the extract density correction factor is as follows: , where ρ is the density of the clarified extract.

[0021] In a further technical solution, the suspending agent is at least one of xanthan gum and sodium carboxymethyl cellulose, and its standard addition ratio is... The concentration is 0.05%~0.2%. The core function of suspending agents is to improve the suspension stability of the dispersed phase and prevent particle sedimentation.

[0022] The thickener is at least one of dextrin and polyethylene glycol, and its standard addition ratio is as follows. The concentration is 0.1%~0.3%, which reduces the particle settling velocity and prolongs the stabilization period by increasing the viscosity of the system.

[0023] The surfactant is at least one of Tween 80 and Span 60, at a reference addition ratio. With a concentration of 0.02% to 0.1%, it can reduce the interfacial tension between oil and water and prevent particle aggregation;

[0024] The baseline addition ratio of each component All three were determined through orthogonal experiments to ensure that the synergistic effect of the three was maximized.

[0025] A further technical solution is to adjust the pressure of the high-pressure homogenization in step S4. With the viscosity of the mixture Satisfying the formula: ;in, It is a high-pressure homogeneous pressure. denoted as ρ, the viscosity of the mixture; α is the viscosity influence coefficient, ranging from 5 to 8 MPa·s / mPa, which is determined experimentally and reflects the pressure increment corresponding to a unit viscosity change; β is the base pressure, ranging from 20 to 30 MPa, ensuring that even at low viscosity, the homogenization pressure can meet the basic particle refinement requirements.

[0026] In a further technical solution, the online monitoring module in step S5 includes a turbidity sensor, a laser particle size analyzer, and a zeta potential meter, with a monitoring frequency of 15 times / minute. This frequency setting can capture changes in the characteristics of the mixture in real time and avoid the accumulation of parameter fluctuations.

[0027] The criteria for closed-loop control are: turbidity ≤ 5 NTU (ensuring clarity), particle size distribution span ≤ 2.0 (ensuring uniform particle dispersion), and absolute value of zeta potential ≥ 25 mV (ensuring colloidal stability).

[0028] Further technical solutions, zeta potential regulation follows the formula: Target ;in, This is the amount of stabilizer to be added. The potential adjustment coefficient has a value range of 0.001~0.003 g / (mV·kg). This coefficient is determined experimentally and reflects the amount of stabilizer required to be added per unit potential deviation and per unit mass of mixed solution. The current zeta potential, target The target zeta potential is set at ±25±30mV, consistent with the judgment criteria. This refers to the mass of the mixture.

[0029] In a further technical solution, in step S1, the primary filter uses a stainless steel filter screen with a pore size of 20~50μm;

[0030] In step S6, the sterilization process uses moist heat sterilization at a temperature of 105~121℃ for 15~30 minutes.

[0031] Further technical solutions also include a transmission linkage structure, which links the gradient membrane separation component, homogenizing equipment and online monitoring module through a PLC control unit to achieve continuous operation of raw material conveying, filtration, homogenization and monitoring;

[0032] The transmission speed is matched with the processing efficiency of each step, following the formula: ;in, Q is the transmission and conveying speed, Q is the processing flow rate, which is determined according to the production scale; S is the cross-sectional area of ​​the conveying pipe, which is determined by the pipe diameter.

[0033] Compared with the prior art, the beneficial effects of the present invention are:

[0034] This invention addresses the problem of "poor clarification and filtration effect and incomplete impurity removal" in existing technologies. It achieves precise stratified removal of impurities of different particle sizes through a three-stage series gradient filtration membrane module design. The pore size of each filtration membrane decreases progressively. The first-stage membrane specifically removes larger particles, while the third-stage membrane precisely captures tiny suspended impurities and colloidal particles, avoiding the shortcomings of single-pore-size filtration membranes that either "incompletely remove impurities or are prone to clogging." Simultaneously, a pressure control module dynamically adapts the filtration pressure of each membrane stage; the smaller the pore size, the higher the corresponding filtration pressure. This ensures that each membrane operates within its optimal pressure range, avoiding both low filtration efficiency due to insufficient pressure and membrane damage or retention of effective components due to excessive pressure. This significantly improves the stability of the clarification effect, resulting in a highly clean clarified extract with a greatly reduced risk of impurity aggregation and precipitation during subsequent storage. Furthermore, this gradient filtration design reduces the probability of membrane module clogging, extends membrane lifespan, and lowers production and maintenance costs.

[0035] This invention addresses the problem of poor adaptability and insufficient stability of existing sedimentation systems by constructing a composite sedimentation system composed of a suspending agent, a thickener, and a surfactant. These three components work synergistically to provide comprehensive sedimentation protection: the suspending agent enhances the suspension stability of the dispersed phase, the thickener reduces particle settling velocity by increasing system viscosity, and the surfactant effectively reduces oil-water interfacial tension and inhibits particle aggregation, resulting in a more comprehensive sedimentation effect than a single sedimentation agent. Furthermore, the amount of sedimentation agent added is not determined empirically but dynamically adjusted based on the quality of the clarified extract, a preset baseline addition ratio, and the density characteristics of the extract. This allows for flexible adjustment of the addition amount for extracts of different densities, avoiding the problems of insufficient or excessive sedimentation caused by traditional empirical addition methods. Through this design, stratification and sedimentation of oral liquids during storage are effectively suppressed, significantly improving product appearance consistency and quality stability, and extending shelf life considerably compared to traditional processes.

[0036] This invention addresses the problem of "lack of real-time monitoring and control mechanisms, resulting in poor product uniformity" in existing technologies. It establishes an online monitoring module comprising a turbidity sensor, a laser particle size analyzer, and a zeta potential meter. This module synchronously detects key indicators such as the clarity of the mixture, particle dispersion uniformity, and colloidal stability at high frequencies, enabling real-time capture of product characteristic changes caused by fluctuations in process parameters and preventing the accumulation of parameter deviations. Simultaneously, it establishes clear quality judgment standards. When monitored indicators exceed the standard range, the control module automatically initiates a closed-loop control process: adjusting homogenization pressure to refine particles for excessive turbidity, optimizing homogenization parameters for uneven particle size distribution, and precisely adding stabilizing agents for substandard zeta potential, forming a complete closed loop of "monitoring-judgment-control-re-monitoring." Furthermore, the PLC control unit links various preparation devices, reducing human intervention and operational errors, significantly minimizing quality differences between different batches and within the same batch, greatly improving the consistency of effective ingredient content, and achieving a higher level of product uniformity.

[0037] This invention addresses the problem of "low process continuity and limited production efficiency" in existing technologies by designing a transmission linkage structure. Through a PLC control unit, it seamlessly connects equipment in each stage, including raw material pretreatment, gradient membrane separation, sedimentation system construction, high-pressure homogenization, online monitoring, and finished product filling. This achieves continuous operation throughout the entire process, eliminating the need for manual raw material handling and significantly shortening the production cycle. Simultaneously, the transmission speed is precisely matched to the processing efficiency of each device, ensuring that raw material delivery matches the processing capacity of each process, avoiding raw material accumulation or insufficient supply caused by poor process connections. Continuous operation not only improves production efficiency but also reduces the risk of contamination from raw materials coming into contact with the external environment during transport, ensuring product cleanliness. Furthermore, the process flow rate can be flexibly adjusted according to production scale, meeting the needs of industrial-scale production and solving the bottleneck of traditional processes that restricts large-scale development.

[0038] To more clearly illustrate the structural features and effects of the present invention, the present invention will be described in detail below with reference to the accompanying drawings and specific embodiments. Attached Figure Description

[0039] Figure 1 This is a schematic diagram of the overall process of the present invention. Detailed Implementation

[0040] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0041] The specific implementation of the present invention will be described in detail below with reference to specific embodiments.

[0042] like Figure 1 As shown in the figure, this invention provides a preparation process for clarifying, stabilizing, and preventing stratification of oral liquids, including the following steps:

[0043] S1. Raw material pretreatment: After crushing and extracting the raw materials for oral liquid, large particulate impurities are removed by primary filtration to obtain primary extract.

[0044] S2. Gradient membrane separation: The primary extract is filtered step by step through gradient filtration membrane modules with different pore sizes to obtain a clarified extract;

[0045] S3. Construction of the stabilizing system: Based on the component characteristics of the clarified extract, a suitable stabilizing agent component is added to it, and the mixture is stirred to obtain a mixture containing the stabilizing system.

[0046] S4. Mixing and homogenization: The mixture containing the stable sedimentation system is sent to a homogenizing device for high-pressure homogenization to improve the uniformity of the system.

[0047] S5. Online monitoring and control: The online monitoring module detects the turbidity, particle size distribution and zeta potential of the mixture in real time. Based on the detection results, the control module performs closed-loop control of the homogenization pressure and the amount of stabilizing agent added.

[0048] S6. Finished product filling: The mixed liquid that meets the requirements after adjustment is sterilized and then filled to obtain the oral liquid finished product.

[0049] In this embodiment, steps S1 to S6 form a complete preparation process, with each step closely linked and coordinated through a transmission linkage structure and control module. Step S1, the raw material pretreatment, lays the foundation for subsequent clarification and sedimentation. Primary filtration removes large particulate impurities, preventing damage to the subsequent gradient membrane separation components and improving the stability of subsequent processes. The selection of a stainless steel filter (pore size 20~50μm) effectively traps larger fibers and particulate impurities without excessively trapping active ingredients, ensuring product efficacy.

[0050] Step S2, gradient membrane separation, is the first core technology, which achieves precise filtration through gradient filtration membrane modules with progressively decreasing pore sizes.

[0051] Step S3, the construction of the stable system, is the second core technology point. As a progression of the first technology, it enhances the stability of the system on the basis of clarification.

[0052] Step S5, online monitoring and control, is the third core technology point. As a further advancement of the first two technologies, it ensures product uniformity and stability through real-time monitoring and closed-loop control.

[0053] The moist heat sterilization process in step S6 can effectively kill microorganisms, ensure product safety, and extend shelf life.

[0054] Specifically, in step S2, the gradient filtration membrane assembly adopts a three-stage series structure, and the pore size of each stage of the filtration membrane meets the requirements. ,in The pore size of the first-stage filter membrane. The pore size of the second-stage filter membrane. The pore size is for the third-stage filtration membrane;

[0055] To achieve precise stratification and retention of impurities of different particle sizes, pore size control follows the formula: Where n=1,2 (corresponding to the aperture change from the first level to the second level, and from the second level to the third level). The pore size of the nth stage filtration membrane (unit: μm) is the pore size of the (n+1)th stage filter membrane (unit: μm), and k is the pore size reduction coefficient (dimensionless), with a value range of 0.3~0.6. Its value can be flexibly adjusted according to the particle size distribution of impurities in the raw material. When the impurity distribution is wide, a smaller value (0.3~0.4) is used to ensure sufficient retention, and a larger value (0.5~0.6) is used when the distribution is concentrated to improve filtration efficiency.

[0056] In this embodiment, the core logic of the formula is to ensure that each stage of the filter membrane only selectively traps impurities within a specific particle size range by decreasing the pore size by a fixed ratio, thereby avoiding clogging or incomplete impurity trapping caused by a single-stage membrane bearing too much filtration load.

[0057] in, The value range is 5~10μm, and it is mainly used to retain larger particulate impurities (such as incompletely crushed raw material particles, fiber bundles, etc.) remaining in the primary extract. The value range is 0.5~1μm, which is used to intercept tiny suspended impurities and colloidal particles to ensure the cleanliness of the final clarified extract.

[0058] Specifically, in step S2, the filtration pressure of the gradient filtration membrane module is dynamically adjusted by the pressure control module, and the adaptation relationship between the filtration pressure and the membrane pore size follows the formula: Where n=1,2,3 (corresponding to three-stage filtration membranes). The filtration pressure of the nth stage filtration membrane (unit: MPa). Reference pressure (unit: MPa). The pore size of the first-stage filtration membrane (unit: μm). The pore size of the nth stage filtration membrane (unit: μm).

[0059] In this embodiment, the design logic of the formula is based on the fluid dynamics principle that "the smaller the membrane pore size, the greater the required filtration pressure". By comparing the ratio with the pore size of the first-stage membrane, it ensures that each stage of the membrane works in the optimal pressure range, which avoids both insufficient pressure leading to low filtration efficiency and excessive pressure causing membrane damage or retention of effective components.

[0060] in, Let n be the filtration pressure of the nth stage filtration membrane. The reference pressure is 0.2~0.5MPa. This reference pressure is determined based on the normal operating pressure of the first-stage membrane to ensure the stability of the initial filtration.

[0061] In actual operation, the pressure control module collects inlet and outlet pressure data of each stage of the membrane in real time. Combined with the current membrane pore size parameters, it automatically calculates and adjusts the filtration pressure of the corresponding stage using a formula. For example, when the pore size of the third-stage membrane... 0.5μm 10μm At 0.2 MPa, the third-stage filtration pressure It can effectively promote the passage of tiny impurities through the membrane pores.

[0062] Specifically, in step S3, the adaptable settling agent component is a composite settling system, including a suspending agent, a thickener, and a surfactant, and the addition amount of each component follows the formula: ;in, The amount of the i-th type of stabilizing agent added (unit: g). The mass of the clarified extract (unit: g) serves as a basic parameter to determine the overall scale of the addition amount; The baseline addition ratio (dimensionless) for the i-th type of stabilizing agent is based on a large number of experiments, which is the foundation for ensuring the stabilizing effect. The formula for calculating the extract density correction factor is as follows: , where ρ is the density of the clarified extract (unit: g / cm³).

[0063] In this embodiment, the core logic of the formula is to achieve a precise match between the amount of stabilizing agent added and the characteristics of the clarifying extract, avoiding the problems of insufficient or excessive stabilization caused by traditional empirical addition. This is achieved by introducing a density correction coefficient. The amount added can be dynamically adjusted for extracts of different densities, improving process adaptability;

[0064] When the density of the extract is greater than 1.02 g / cm³, If the value is greater than 1, increase the amount of stabilizing agent to address the sedimentation risk of high-density systems; otherwise, reduce the amount appropriately.

[0065] In the operation procedure, the density sensor is first used to detect the concentration of the clarified extract. Value, calculated , and then combine and preset The precise amount of each stabilizer is calculated using a formula, and the quantitative addition is completed by an automatic addition device.

[0066] Specifically, the suspending agent is at least one of xanthan gum and sodium carboxymethyl cellulose, and its standard addition ratio is... The concentration is 0.05%~0.2%. The core function of suspending agents is to improve the suspension stability of the dispersed phase and prevent particle sedimentation.

[0067] The thickener is at least one of dextrin and polyethylene glycol, and its standard addition ratio is as follows. The concentration is 0.1%~0.3%, which reduces the particle settling velocity and prolongs the stabilization period by increasing the viscosity of the system.

[0068] The surfactant is at least one of Tween 80 and Span 60, at a reference addition ratio. With a concentration of 0.02% to 0.1%, it can reduce the interfacial tension between oil and water and prevent particle aggregation;

[0069] The baseline addition ratio of each component All three were determined through orthogonal experiments to ensure that the synergistic effect of the three was maximized.

[0070] In this embodiment, during the operation steps, according to the formula , After calculating the amount of each component to be added, add them in the following order: first add the suspending agent, then the thickener, and finally the surfactant. Stir for 5 to 10 minutes after each component is added to ensure that each component is fully dissolved and evenly dispersed to form a stable composite sedimentation system.

[0071] Specifically, the pressure of high-pressure homogenization in step S4 With the viscosity of the mixture Satisfying the formula: ;in, High pressure homogeneous pressure (unit: MPa). Here, denoted as ρ, is the viscosity of the mixture (unit: mPa·s). 'a' is the viscosity influence coefficient, ranging from 5 to 8 MPa·s / mPa. This coefficient is determined experimentally and reflects the pressure increment corresponding to a unit change in viscosity. 'b' is the base pressure, ranging from 20 to 30 MPa, ensuring that even at low viscosity, the homogenization pressure can meet the basic particle refinement requirements.

[0072] In this embodiment, the design logic of the formula is based on the principle that "the greater the viscosity of the mixture, the greater the required homogenization pressure". The influence of viscosity on homogenization pressure is quantified through a linear relationship to ensure the stability of the homogenization effect and avoid problems such as insufficient particle refinement or system damage caused by viscosity fluctuations.

[0073] In the operation process, the homogenizer first detects the viscosity of the mixture using a built-in viscosity sensor. The value is transmitted to the control module, which then automatically calculates the corresponding value using a formula. The value is then adjusted, and the working pressure of the homogenizer is adjusted. Under this pressure, the mixture passes through the gap of the homogenizer valve and is subjected to shearing, impact, and cavitation, which further refines the particles and disperses them evenly, improving the homogeneity of the system. For example, when the viscosity of the mixture is... When a = 6 MPa·s / mPa and b = 25 MPa, the pressure It can effectively refine particles to the target particle size range.

[0074] Specifically, the oral liquid clarification, sedimentation stabilization and anti-stratification preparation process according to claim 1 is characterized in that the online monitoring module in step S5 includes a turbidity sensor, a laser particle size analyzer and a zeta potential meter, and the monitoring frequency is 15 times / minute. This frequency setting can capture changes in the characteristics of the mixture in real time and avoid the accumulation of parameter fluctuations.

[0075] The criteria for closed-loop control are: turbidity ≤ 5 NTU (ensuring clarity), particle size distribution span ≤ 2.0 (ensuring uniform particle dispersion), and absolute value of zeta potential ≥ 25 mV (ensuring colloidal stability).

[0076] In this embodiment, the judgment criterion is determined based on the oral liquid quality standard and is a core indicator to ensure the stability of the finished product. When the monitored value exceeds the judgment criterion, the control module automatically starts the closed-loop control process: if the turbidity exceeds the standard, the homogenization pressure is adjusted first to further refine the particles; if the particle size distribution Span exceeds the standard, the number of homogenization times is increased or the homogenization pressure is adjusted; if the zeta potential does not meet the standard, the corresponding stabilizing agent is added.

[0077] In the operation process, the online monitoring module completes the synchronous detection of three indicators every 15 minutes and transmits the data to the control module. The control module compares the data with the judgment standard. If all indicators meet the standard, the process proceeds to the next step. If any indicator exceeds the standard, the corresponding control measures are immediately activated. After the control is completed, the monitoring is repeated until all indicators meet the requirements, forming a closed-loop process of "monitoring-judgment-control-re-monitoring".

[0078] Specifically, zeta potential regulation follows the formula: target ;in, This refers to the amount of stabilizing agent to be added (unit: g). The potential adjustment coefficient has a value range of 0.001~0.003 g / (mV·kg). This coefficient is determined experimentally and reflects the amount of stabilizer required to be added per unit potential deviation and per unit mass of mixed solution. The current zeta potential (unit: mV), target The target zeta potential (unit: mV) is set at ±25±30mV, consistent with the judgment criteria. Mass of the mixture (unit: kg).

[0079] In this embodiment, the core logic of the formula is to quantify the relationship between the zeta potential deviation and the amount of stabilizing agent added, so as to achieve precise control of the zeta potential. The principle is that the change of zeta potential is positively correlated with the amount of stabilizing agent added. The absolute value deviation ensures the accuracy of the control direction (regardless of whether the current potential is positive or negative, targeted addition is made).

[0080] In the closed-loop control process, when monitoring When the absolute value is less than 25mV, the control module calculates using a formula. For example, when , ,Target , hour, Then, the stabilizer addition device is controlled to precisely add 1g of stabilizer, and after stirring and mixing, the zeta potential is detected again until the target value is reached.

[0081] Specifically, in step S1, the primary filtration uses a stainless steel filter screen with a pore size of 20~50μm. The core function of this pore size setting is to remove impurities with larger particle sizes (such as fibers, blocky raw material residues, etc.) in the extract, and to prevent such large particles from entering the subsequent gradient membrane separation components, causing membrane pore blockage or membrane surface scratches, thus laying the foundation for subsequent precise filtration.

[0082] In step S6, the sterilization process adopts moist heat sterilization, with a sterilization temperature of 105~121℃ and a sterilization time of 15~30 minutes. This parameter setting is based on the principle of microbial killing. The matching of temperature and time can effectively kill bacteria, mold and other microorganisms in the mixture, while avoiding the loss of effective ingredients in the oral liquid due to excessively high temperature or excessive time.

[0083] In this embodiment, during the operation steps, the primary extract is pumped into a stainless steel filter screen filtration device. The filter screen has a detachable structure for easy cleaning and replacement. After filtration, the filter screen is inspected regularly to ensure the filtration effect.

[0084] In the operation process, the sterilization equipment first heats the mixture to the set temperature, holds it for a corresponding time, and then quickly cools it down to room temperature through the cooling system to prevent secondary contamination.

[0085] Specifically, it also includes a transmission linkage structure, which links the gradient membrane separation component, homogenizing equipment and online monitoring module through a PLC control unit to realize continuous operation of raw material conveying, filtration, homogenization and monitoring;

[0086] The transmission speed is matched with the processing efficiency of each step, following the formula: ;in, Q is the transmission speed (unit: m / s), Q is the processing flow rate (unit: m³ / s), which is determined according to the production scale (e.g., Q = 0.0001~0.0005 m³ / s for large-scale production); S is the cross-sectional area of ​​the conveying pipe (unit: m²), which is determined by the pipe diameter.

[0087] In this embodiment, the design logic of the formula is based on the principle of fluid transport continuity, ensuring that the raw material transport speed matches the processing capacity of each device, avoiding problems such as raw material accumulation or insufficient supply, and ensuring the smoothness of continuous production.

[0088] During operation, the PLC control unit collects the processing flow rate Q data of each device in real time, and automatically calculates the corresponding flow rate Q using a formula, combined with the S parameters of the conveying pipeline. The value is then used to adjust the speed of the transmission and conveying device, for example, when Q = 0.0002 m³ / s and S = 0.0001 m². This ensures that raw materials are transferred between devices at a stable speed, enabling continuous operation throughout the entire process of "raw material pretreatment - gradient filtration - sedimentation addition - homogenization - monitoring - filling", reducing human intervention errors and improving production efficiency.

[0089] Working principle and usage process of this invention:

[0090] Based on the core logic of "precise separation - stable construction - real-time control - continuous linkage", this system systematically solves the problems of clarification, sedimentation stabilization, and anti-stratification in the preparation and storage of oral liquids through multi-step collaboration and multi-parameter quantitative adaptation. The working principles of each key link are as follows:

[0091] Raw material pretreatment and primary filtration: Remove large particulate impurities, laying the foundation for subsequent precision processing;

[0092] Working Logic: After the oral liquid raw materials are crushed and extracted, residual large-particle impurities (usually greater than 20μm), such as incompletely crushed particles and fiber bundles, can easily cause membrane module clogging or scratches if directly entering the subsequent fine filtration stage. Therefore, a detachable stainless steel filter with a pore size of 20~50μm is used for primary filtration. Utilizing the principle of physical interception, this method specifically removes these large-particle impurities while avoiding excessive retention of active ingredients due to excessively small filter pore size. The detachable design of the filter facilitates cleaning and replacement, ensuring stable filtration efficiency.

[0093] Gradient membrane separation system: enables precise stratification and retention of impurities of different particle sizes, resulting in a highly purified and clear extract;

[0094] Staged filtration principle: It adopts a three-stage series filtration membrane module, following the formula of decreasing pore size. ( With a fixed ratio of 0.3 to 0.6, each stage of the membrane is designed to retain impurities within a specific particle size range through a gradual change in pore size. The first-stage membrane (5-10 μm) retains larger suspended particles, while the second-stage membrane, based on the pore size of the first stage, retains larger suspended particles. The values ​​show that the third-stage membrane (0.5~1μm) traps medium-sized impurities, while the third-stage membrane traps tiny suspended impurities and colloidal particles, forming a "coarse to fine" step-like filtration, thus avoiding clogging or incomplete trapping caused by overloading the single-stage membrane.

[0095] Pressure adaptation principle: Based on the principle in fluid mechanics that "the smaller the membrane pore size, the greater the fluid permeation resistance," a filtration pressure formula is designed. ( (The reference pressure is 0.2~0.5MPa). By adjusting the ratio of the pressure to the pore size of the first-stage membrane, the filtration pressure of each stage of the membrane is dynamically adjusted to ensure that the membrane with the smaller pore size receives the greater driving force. This avoids both insufficient pressure leading to low filtration efficiency and excessive pressure causing membrane damage or retention of effective components, thus enabling each stage of the membrane to operate stably within the optimal pressure range.

[0096] Construction of a composite settling system: By using a precisely matched combination of settling agents, particle sedimentation and aggregation are inhibited, and the thermodynamic stability of the system is improved.

[0097] Component synergistic principle: A composite system of "suspending agent + thickener + surfactant" is adopted, and the three form a synergistic effect: the suspending agent (xanthan gum, sodium carboxymethyl cellulose) forms a three-dimensional network structure through molecular chain entanglement, which improves the suspension stability of the dispersed phase; the thickener (dextrin, polyethylene glycol) increases the viscosity of the system and reduces the particle settling velocity according to Stokes' law; the surfactant (Tween 80, Span 60) reduces the oil-water interfacial tension, reduces the van der Waals attraction between particles, and prevents particle aggregation.

[0098] Precise addition principle: based on the quality of the clarified extract. The standard addition ratio of each stabilizer (Determined by orthogonal experiments), a density correction coefficient is introduced. Through formula Calculate the precise dosage; when the extract density is greater than 1.02 g / cm³, the risk of sedimentation in the system increases. If the value is greater than 1, the amount of stabilizing agent added will be automatically increased; otherwise, it will be reduced, avoiding the problems of insufficient or excessive stabilization caused by traditional experience-based addition, and achieving precise matching between the stabilization system and the characteristics of the extract.

[0099] High-pressure homogenization: refines particle size and improves system uniformity, providing support for the stable settling system to function;

[0100] Pressure adaptation principle: The viscosity of the mixture directly affects the homogenization effect; the higher the viscosity, the stronger the shear and impact forces required for particle refinement. Therefore, a homogenization pressure formula is designed. ( It is 5~8 MPa·s / mPa. (20~30MPa), the effect of viscosity on pressure is quantified through a linear relationship; the homogenizer has a built-in viscosity sensor for real-time detection. The control module automatically calculates the appropriate pressure, so that the mixture passes through the gap of the homogenizing valve under this pressure and is subjected to the triple action of shearing, impact and cavitation, which refines the particles to a uniform particle size range and reduces the risk of sedimentation and stratification caused by particle size differences.

[0101] Online monitoring and closed-loop control: Real-time capture of changes in product characteristics, and dynamic control to ensure quality stability;

[0102] Monitoring principle: An online monitoring module consisting of a turbidity sensor, a laser particle size analyzer, and a zeta potential meter is used to synchronously detect key indicators at a frequency of 15 times / minute: turbidity reflects clarity, particle size distribution span reflects particle dispersion uniformity, and zeta potential reflects colloidal stability (the larger the absolute value, the stronger the colloidal stability).

[0103] Control principle: Set judgment criteria (turbidity ≤ 5 NTU, Span ≤ 2.0, zeta potential ≥ 25 mV) to form a closed-loop process of "monitoring-judgment-control-re-monitoring".

[0104] a. When turbidity exceeds the standard, the particles are further refined by increasing the homogenization pressure to reduce the turbidity of the system;

[0105] b. When the particle size distribution span exceeds the standard, increase the number of homogenization cycles or adjust the homogenization pressure to optimize the particle dispersion effect;

[0106] c. When the zeta potential is not met, the target is determined according to the formula. ( Precise addition of stabilizer (0.001~0.003 g / (mV·kg)) improves colloidal stability by adjusting the interfacial charge of the system.

[0107] Transmission linkage and continuous operation: achieve seamless connection between various processes, reduce human intervention errors, and improve production efficiency;

[0108] Linkage Principle: A continuous production chain is constructed by connecting the gradient membrane separation component, homogenizing equipment, and online monitoring module in series via a PLC control unit. Based on the principle of continuous fluid transport, a transmission speed formula is designed. ( To handle traffic, (The cross-sectional area of ​​the conveying pipeline) is used to match the raw material conveying speed with the processing capacity of each piece of equipment in real time, so as to avoid raw material accumulation or insufficient supply and ensure the smooth operation of the entire process of "raw material pretreatment - gradient filtration - stabilizing addition - homogenization - monitoring - filling".

[0109] Sterilization principle: Moist heat sterilization at 105~121℃ for 15~30 minutes is used to destroy the protein and nucleic acid structure of microorganisms by using high temperature and high pressure, effectively killing harmful microorganisms such as bacteria and mold. At the same time, it is rapidly cooled to room temperature to avoid loss of effective ingredients due to prolonged high temperature treatment, thus ensuring product safety and efficacy.

[0110] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A preparation process for clarifying, stabilizing, and preventing stratification of oral liquids, characterized in that, Includes the following steps: S1. Raw material pretreatment: After crushing and extracting the raw materials for oral liquid, large particulate impurities are removed by primary filtration to obtain primary extract. S2. Gradient membrane separation: The primary extract is filtered step by step through gradient filtration membrane modules with different pore sizes to obtain a clarified extract; S3. Construction of the stabilizing system: Based on the component characteristics of the clarified extract, a suitable stabilizing agent component is added to it, and the mixture is stirred to obtain a mixture containing the stabilizing system. S4. Mixing and homogenization: The mixture containing the stable sedimentation system is sent to a homogenizing device for high-pressure homogenization to improve the uniformity of the system. S5. Online monitoring and control: The online monitoring module detects the turbidity, particle size distribution and zeta potential of the mixture in real time. Based on the detection results, the control module performs closed-loop control of the homogenization pressure and the amount of stabilizing agent added. S6. Finished product filling: The mixed liquid that meets the requirements after adjustment is sterilized and then filled to obtain the oral liquid finished product.

2. The oral liquid clarification, sedimentation stabilization, and anti-stratification preparation process according to claim 1, characterized in that, In step S2, the gradient filtration membrane assembly adopts a three-stage series structure, and the pore size of each stage of the filtration membrane meets the requirements. ,in The pore size of the first-stage filter membrane. The pore size of the second-stage filter membrane. The pore size is for the third-stage filtration membrane; To achieve precise stratification and retention of impurities of different particle sizes, pore size control follows the formula: Where n=1,2 (corresponding to the aperture change from the first level to the second level, and from the second level to the third level). Let n be the pore size of the nth stage filter membrane. denoted as pore size of the (n+1)th stage filter membrane, and k is the pore size reduction coefficient, ranging from 0.3 to 0.

6. Its value can be flexibly adjusted according to the particle size distribution of impurities in the raw material. When the impurity distribution is wide, a smaller value (0.3 to 0.4) is used to ensure sufficient interception, and a larger value (0.5 to 0.6) is used when the distribution is concentrated to improve filtration efficiency.

3. The oral liquid clarification, sedimentation stabilization, and anti-stratification preparation process according to claim 2, characterized in that, In step S2, the filtration pressure of the gradient filtration membrane module is dynamically adjusted by the pressure control module, and the adaptation relationship between the filtration pressure and the membrane pore size follows the formula: Where n=1,2,3 (corresponding to three-stage filtration membranes). The filtration pressure of the nth stage filtration membrane. As the reference pressure, The pore size of the first-stage filter membrane. Let be the pore size of the nth stage filter membrane.

4. The oral liquid clarification, sedimentation stabilization, and anti-stratification preparation process according to claim 1, characterized in that, In step S3, the adaptable settling agent component is a composite settling system, including a suspending agent, a thickener, and a surfactant. The addition amount of each component follows the formula: ;in, Let i be the amount of the i-th type of stabilizing agent added. To clarify the quality of the extract, the overall scale of the addition amount is determined as a basic parameter; The baseline addition ratio for the i-th type of stabilizing agent is a basic ratio determined by a large number of experiments, which ensures the stabilizing effect. The formula for calculating the extract density correction factor is as follows: , where ρ is the density of the clarified extract.

5. The oral liquid clarification, sedimentation stabilization, and anti-stratification preparation process according to claim 4, characterized in that, The suspending agent is at least one of xanthan gum and sodium carboxymethyl cellulose, and its standard addition ratio is as follows. The concentration is 0.05%~0.2%. The core function of suspending agents is to improve the suspension stability of the dispersed phase and prevent particle sedimentation. The thickener is at least one of dextrin and polyethylene glycol, and its standard addition ratio is as follows. The concentration is 0.1%~0.3%, which reduces the particle settling velocity and prolongs the stabilization period by increasing the viscosity of the system. The surfactant is at least one of Tween 80 and Span 60, at a reference addition ratio. With a concentration of 0.02% to 0.1%, it can reduce the interfacial tension between oil and water and prevent particle aggregation; The baseline addition ratio of each component All three were determined through orthogonal experiments to ensure that the synergistic effect of the three was maximized.

6. The oral liquid clarification, sedimentation stabilization, and anti-stratification preparation process according to claim 1, characterized in that, Pressure during high-pressure homogenization in step S4 With the viscosity of the mixture Satisfying the formula: ;in, It is a high-pressure homogeneous pressure. denoted as ρ, the viscosity of the mixture; α is the viscosity influence coefficient, ranging from 5 to 8 MPa·s / mPa, which is determined experimentally and reflects the pressure increment corresponding to a unit viscosity change; β is the base pressure, ranging from 20 to 30 MPa, ensuring that even at low viscosity, the homogenization pressure can meet the basic particle refinement requirements.

7. The oral liquid clarification, sedimentation stabilization, and anti-stratification preparation process according to claim 1, characterized in that, The online monitoring module in step S5 includes a turbidity sensor, a laser particle size analyzer, and a zeta potential meter. The monitoring frequency is 15 times / minute. This frequency setting can capture changes in the characteristics of the mixture in real time and avoid the accumulation of parameter fluctuations. The criteria for closed-loop control are: turbidity ≤ 5 NTU (ensuring clarity), particle size distribution span ≤ 2.0 (ensuring uniform particle dispersion), and absolute value of zeta potential ≥ 25 mV (ensuring colloidal stability).

8. The oral liquid clarification, sedimentation stabilization, and anti-stratification preparation process according to claim 1, characterized in that, Zeta potential regulation follows the formula: target ;in, This is the amount of stabilizer to be added. The potential adjustment coefficient has a value range of 0.001~0.003 g / (mV·kg). This coefficient is determined experimentally and reflects the amount of stabilizer required to be added per unit potential deviation and per unit mass of mixed solution. The current zeta potential, target The target zeta potential is set at ±25±30mV, consistent with the judgment criteria. This refers to the mass of the mixture.

9. The oral liquid clarification, sedimentation stabilization, and anti-stratification preparation process according to claim 1, characterized in that, In step S1, the primary filtration uses a stainless steel filter screen with a pore size of 20~50μm; In step S6, the sterilization process uses moist heat sterilization at a temperature of 105~121℃ for 15~30 minutes.

10. The oral liquid clarification, sedimentation stabilization, and anti-stratification preparation process according to claim 1, characterized in that, It also includes a transmission linkage structure, which links the gradient membrane separation component, homogenizing equipment and online monitoring module through a PLC control unit to realize continuous operation of raw material conveying, filtration, homogenization and monitoring; The transmission speed is matched with the processing efficiency of each step, following the formula: ;in, Q is the transmission and conveying speed, Q is the processing flow rate, which is determined according to the production scale; S is the cross-sectional area of ​​the conveying pipe, which is determined by the pipe diameter.

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