Preparation process of embryo extract capsule containing tea polyphenol

Abstract

The invention relates to the technical field of embryo extract capsule preparation, in particular to a tea polyphenol-containing embryo extract capsule preparation process, which comprises: weighing tea polyphenol, beta-cyclodextrin and an embryo extract according to a preset ratio; determining the embedding molar ratio of beta-cyclodextrin based on the EGCG purity value, embedding tea polyphenol, beta-cyclodextrin and the embryo extract to obtain an embedding reaction solution, and adjusting the embedding molar ratio according to the turbidity change rate and the pH deviation degree; determining the concentration of a wet granulation adhesive based on the activity sensitivity coefficient so as to carry out wet granulation, and determining and adjusting the addition rate of the adhesive according to the torque endpoint value and the particle size distribution dispersion; a capsule shell is filled with the dry particles to obtain a target capsule, the state of the capsule is judged based on the dissolution rate deviation value and the capsule shell integrity index, and an optimization mode is determined according to the embryo activity abnormity degree to adjust and optimize the embedding temperature or the drying duration; the adjusted and optimized embryo extract capsule is obtained. The preparation stability of the embryo extract capsule is improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of embryonic factor capsule preparation, and particularly relates to a preparation process of an embryonic factor capsule containing tea polyphenols. BACKGROUND

[0002] The embryonic factor capsule containing tea polyphenols is widely applied in the fields of functional food and health products due to the combination of the antioxidant function of tea polyphenols and the biological activity of embryonic factor. However, tea polyphenols are easily oxidized or degraded by environmental factors, and there is a complex correlation among the embedding efficiency of tea polyphenols and β-cyclodextrin, the activity retention rate of embryonic factor extract, and the capsule forming property. It is difficult to accurately control the multi-dimensional quality indicators by using the traditional preparation method.

[0003] Chinese patent application publication No. CN1476830A discloses a tea polyphenol soft capsule, which comprises a capsule core and a capsule shell. The capsule core contains, by weight percentage, 5-60% of tea polyphenols, 0-20% of soybean phospholipid, 0-2% of vitamin E, 0-15% of a capsule stabilizer, and the balance of a diluent. The capsule shell contains, by weight percentage of raw materials, 35-45% of gelatin, 0-3% of polyethylene glycol 400, 18-22% of a plasticizer, 0.08-0.11% of a preservative, 0-1% of a screening agent, 0-0.35% of a pigment, 0-0.1% of a flavoring agent, and the balance of water. The preparation process of the above tea polyphenol soft capsule comprises capsule shell preparation, capsule core preparation, and soft capsule compression.

[0004] However, the prior art has the following problems: the capsule preparation process is not monitored and regulated in real time, resulting in low embedding efficiency, poor capsule shell stability, and activity attenuation of embryonic factor, thereby causing the problem of low stability of embryonic factor capsule preparation. SUMMARY

[0005] Therefore, the present application provides a preparation process of an embryonic factor capsule containing tea polyphenols to overcome the problem in the prior art that the capsule preparation process is not monitored and regulated in real time, resulting in low embedding efficiency, poor capsule shell stability, and activity attenuation of embryonic factor, thereby causing the problem of low stability of embryonic factor capsule preparation.

[0006] To achieve the above-mentioned purpose, the present application provides a preparation process of an embryonic factor capsule containing tea polyphenols, comprising the following steps:

[0007] Tea polyphenols, β-cyclodextrin, and embryonic factor extract are weighed according to a preset ratio;

[0008] The embedding molar ratio of β-cyclodextrin is determined based on the EGCG purity value of the tea polyphenols, the tea polyphenols, the β-cyclodextrin, and the embryonic factor extract are embedded to obtain an embedding reaction solution, and the embedding molar ratio is adjusted according to the turbidity change rate and the pH offset degree of the embedding reaction solution;

[0009] determining a wet granulation binder concentration based on the activity sensitivity coefficient of the embryo extract to perform wet granulation, and determining an adjustment of the binder addition rate based on a torque end point value and a particle size distribution dispersion of the granulation soft material obtained by wet granulation;

[0010] filling the dry granules obtained by drying and sieving the granulation soft material into capsule shells to obtain target capsules, determining a capsule state based on a dissolution deviation value and a capsule shell integrity index of the target capsules, and determining an optimization mode for adjusting and optimizing the drying duration or the embedding temperature based on an activity abnormality degree of the embryo extract corresponding to the capsule state;

[0011] obtaining the embryo extract capsules after the adjustment and optimization.

[0012] Further, determining a beta-cyclodextrin embedding molar ratio based on an EGCG purity value of the tea polyphenol;

[0013] The beta-cyclodextrin embedding molar ratio and the EGCG purity value are in a positive correlation.

[0014] Further, adjusting the beta-cyclodextrin embedding molar ratio for an abnormal reaction process node based on a turbidity change rate and a pH offset degree of an embedding reaction solution, wherein the adjustment of the beta-cyclodextrin embedding molar ratio for a single abnormal reaction process node comprises:

[0015] If the comparison result that the turbidity change rate is greater than or equal to a preset turbidity change rate or the pH offset degree is greater than or equal to a preset pH offset degree determines to decrease the beta-cyclodextrin embedding molar ratio;

[0016] If the comparison result that the turbidity change rate is less than a preset turbidity change rate and the pH offset degree is less than a preset pH offset degree determines to increase the beta-cyclodextrin embedding molar ratio;

[0017] The abnormal reaction process node is a reaction process node with an evaluation deviation value greater than a preset evaluation deviation value.

[0018] Further, determining a wet granulation binder concentration based on the activity sensitivity coefficient of the embryo extract;

[0019] The binder concentration and the activity sensitivity coefficient of the embryo extract are in a positive correlation.

[0020] Further, determining to increase the binder addition rate based on a comparison result that the torque end point value of the granulation soft material is less than a preset torque end point value or the particle size distribution dispersion is greater than or equal to a preset particle size distribution dispersion.

[0021] Further, the reducing of the binder adding rate is determined based on the comparison result that the torque end point value of the granulation soft material is greater than or equal to a preset torque end point value and the particle size distribution dispersion is less than a preset particle size distribution dispersion.

[0022] Further, the embryo capsule is determined as the first capsule state based on the comparison result that the dissolution deviation value of the filled capsule is greater than or equal to a preset dissolution deviation value and the capsule shell integrity index is greater than or equal to a preset capsule shell integrity index.

[0023] Further, the embryo capsule is determined as the second capsule state based on the comparison result that the dissolution deviation value of the filled capsule is less than a preset dissolution deviation value but the capsule shell integrity index is less than a preset capsule shell integrity index.

[0024] Further, the drying time length is adjusted based on the comparison result that the embryo active abnormality degree of the corresponding capsule state is less than or equal to a preset embryo active abnormality degree.

[0025] Further, the embedding temperature is adjusted based on the comparison result that the embryo active abnormality degree of the corresponding capsule state is greater than a preset embryo active abnormality degree.

[0026] Compared with the prior art, the present application has the beneficial effects that the present application determines the optimal embedding molar ratio through the tea polyphenol EGCG purity value, improves the stability and bioavailability of the active ingredients, ensures that the active ingredients of the embryo remain in the optimal active state during storage and use, adjusts the binder concentration of the wet granulation according to the activity sensitivity coefficient of the embryo extract, and optimizes the binder adding rate, which helps to obtain granulation soft material with uniform particle size and good flowability, thereby improving the uniformity and filling efficiency of the capsule content, monitoring the turbidity change rate and pH deviation of the embedding reaction liquid, the torque end point value and the particle size distribution dispersion of the granulation soft material, real-time regulation of the preparation process, improving the stability and consistency of the embryo capsule, and state determination according to the dissolution deviation value and the capsule shell integrity index of the target capsule, and targeted adjustment of the drying time length or the embedding temperature, which improves the stability of the embryo capsule preparation process.

[0027] Further, the present application optimizes the stability of the tea polyphenol-embryo complex by dynamically adjusting the β-cyclodextrin embedding molar ratio, real-time monitors the embedding reaction process by using the turbidity change rate and the pH deviation, dynamically adjusts the embedding ratio for abnormal nodes to improve the embedding efficiency, improves the active ingredient loading rate and the anti-degradation ability, improves the embedding abnormality capture precision, reduces the batch-to-batch quality fluctuation, enhances the sustained-release characteristics of the embryo, and reduces the risk of active loss.

[0028] Furthermore, by monitoring the torque endpoint value and particle size distribution dispersion of the granulated soft material in real time, the present invention dynamically adjusts the addition rate of the binder during the wet granulation process, thereby improving the adaptability of the granulation process, reducing the failure rate of subsequent filling processes due to particle quality fluctuations, improving batch consistency, and thus improving the stability of the embryonic capsule preparation process.

[0029] Furthermore, this invention determines the product quality status by monitoring the dissolution deviation value and shell integrity index of the filled capsules. For the first state where the dissolution performance is abnormal but the shell is well sealed, the drying time is adjusted. For the second state where the dissolution is qualified but the shell is damaged, the embedding temperature is adjusted. This avoids the one-sidedness of evaluation by a single index, improves production efficiency, enhances the adaptability of the production system to raw material fluctuations through dynamic adjustment of the preparation process, and reduces the risk of microbial invasion through real-time monitoring, thereby improving the stability of the embryonic capsule preparation process.

[0030] Furthermore, by determining the capsule state and then selectively optimizing the drying time or encapsulation temperature based on the degree of abnormality in embryonic activity, this invention achieves precise process intervention, improves the bioactivity of embryonic cells, reduces the damage to the embryonic cell structure caused by high temperatures, shortens the response cycle to quality anomalies, and thus improves the stability of the embryonic cell capsule preparation process. Attached Figure Description

[0031] Figure 1 This is a flowchart illustrating the preparation process of embryonic capsules containing tea polyphenols according to an embodiment of the present invention;

[0032] Figure 2 This is a flowchart illustrating the adjustment of the β-cyclodextrin encapsulation molar ratio at abnormal reaction process nodes according to an embodiment of the present invention;

[0033] Figure 3 A flowchart for determining the rate of adhesive addition in an embodiment of the present invention;

[0034] Figure 4 A flowchart for determining the optimization method in an embodiment of the present invention. Detailed Implementation

[0035] To make the objectives and advantages of the present invention clearer, the present invention will be further described below with reference to embodiments; it should be understood that the specific embodiments described herein are merely for explaining the present invention and are not intended to limit the present invention.

[0036] Preferred embodiments of the present invention will now be described with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are merely illustrative of the technical principles of the present invention and are not intended to limit the scope of protection of the present invention.

[0037] It should be noted that the data in this embodiment are all derived from a comprehensive analysis and evaluation of historical test data and corresponding historical test results from the three months prior to this test. Those skilled in the art will understand that the determination of the above-mentioned parameters for any single item in this invention can be achieved by selecting the value with the highest percentage based on the data distribution as the preset standard parameter, using weighted summation to obtain the value as the preset standard parameter, substituting each historical data point into a specific formula and using the value obtained from that formula as the preset standard parameter, or other selection methods, as long as the invention can clearly define different specific situations in the single-item judgment process through the obtained values.

[0038] Please see Figure 1 The diagram shows a flowchart of the preparation process of embryonic capsules containing tea polyphenols according to an embodiment of the present invention.

[0039] The preparation process of embryonic capsules containing tea polyphenols according to embodiments of the present invention includes:

[0040] Step S1: Weigh out tea polyphenols, β-cyclodextrin and embryonic extract in a preset ratio;

[0041] Step S2: Determine the β-cyclodextrin encapsulation molar ratio based on the EGCG purity value of the tea polyphenols, encapsulate the tea polyphenols, the β-cyclodextrin and the embryonic extract to obtain an encapsulation reaction solution, and adjust the encapsulation molar ratio according to the turbidity change rate and pH shift of the encapsulation reaction solution.

[0042] Step S3: Determine the wet granulation binder concentration based on the activity sensitivity coefficient of the embryo extract for wet granulation, and determine the binder addition rate based on the torque endpoint value and particle size distribution dispersion of the granulated soft material obtained by wet granulation.

[0043] Step S4: The dry granules obtained after drying and sieving the granulated soft material are filled into the capsule shell to obtain the target capsule. The capsule state is determined based on the dissolution deviation value and capsule shell integrity index of the target capsule. The optimization method is determined based on the abnormality of embryonic activity of the corresponding capsule state, which is to adjust and optimize the drying time or encapsulation temperature.

[0044] Step S5 yields the adjusted and optimized embryonic capsules.

[0045] This invention determines the optimal encapsulation molar ratio by using the purity value of tea polyphenol EGCG, thereby improving the stability and bioavailability of the active ingredients and ensuring that the effective components of embryonic extract maintain their optimal activity state during storage and use. Adjusting the wet granulation binder concentration based on the activity sensitivity coefficient of the embryonic extract and optimizing the binder addition rate helps obtain granulated soft materials with uniform particle size and good flowability, thus improving the uniformity and filling efficiency of the capsule contents. Monitoring the turbidity change rate and pH shift of the encapsulation reaction solution, as well as the torque endpoint value and particle size distribution dispersion of the granulated soft material, enables real-time control of the preparation process, improving the stability and consistency of embryonic extract capsules. State determination is based on the dissolution deviation value and shell integrity index of the target capsules, and the drying time or encapsulation temperature is adjusted accordingly, further improving the stability of the embryonic extract capsule preparation process.

[0046] The application scenario of this invention is the preparation of embryonic capsules containing tea polyphenols. This invention has several historical records, each of which records at least one historical process of preparing embryonic capsules containing tea polyphenols, including EGCG purity, β-CD encapsulation molar ratio, turbidity change rate, activity sensitivity coefficient, binder concentration, dissolution deviation value, capsule shell integrity index, and embryonic activity abnormality. Each historical record has a corresponding qualified mark, which records whether the preparation process of embryonic capsules containing tea polyphenols meets the user's requirements. The qualified mark can be recorded manually. It is understood that the user can determine whether the preparation process of embryonic capsules containing tea polyphenols meets the requirements based on self-defined indicators. Self-defined indicators can be, but are not limited to, dissolution test values, which will not be elaborated here. The dissolution test value is the amount of dissolution measured by the paddle method, with a rotation speed of 50 rpm, a medium of 900 mL, pH 6.8 phosphate buffer, a temperature of 37±0.5℃, and a sampling time of 15 min.

[0047] The preparation process of the target capsule is as follows: tea polyphenols, β-cyclodextrin (β-CD), and embryonic extract are prepared in a preset ratio; the β-cyclodextrin encapsulation molar ratio (β-CD encapsulation molar ratio) is determined based on the EGCG purity value of tea polyphenols, and the encapsulation molar ratio is adjusted based on the turbidity change rate and pH shift of the encapsulation reaction solution; the wet granulation binder concentration is determined based on the activity sensitivity coefficient of embryonic extract; the binder addition rate is adjusted based on the torque endpoint value and particle size distribution dispersion of the granulation soft material; the granulation sieve mesh size is determined based on the moisture gradient difference of dry particles; the capsule filling machine parameters are determined based on the angle of repose and bulk density of the total mixed particles; the capsule state is determined based on the dissolution deviation value and shell integrity index of the filled capsules; and the optimization process is initiated based on the capsule state.

[0048] This invention sets target coefficients and relevant thresholds. The correspondence between the target coefficients and relevant thresholds is expressed by a weighting formula: Target coefficient = Weighting coefficient × Relevant threshold. Specifically, this invention uses the following as target coefficients: β-CD encapsulation molar ratio, increase in β-CD encapsulation molar ratio at a single reaction process node, decrease in β-CD encapsulation molar ratio at a single reaction process node, binder concentration, increase in binder addition rate, increase in granulation sieve mesh size, decrease in angle of repose, increase in bulk density, adjustment value of disintegrant ratio, humidity adjustment range, and lubricant dosage adjustment value. EGCG purity, turbidity change rate, pH shift, activity sensitivity coefficient, torque endpoint value, particle size distribution dispersion, dissolution deviation, and capsule integrity index. The abnormality of embryonic activity is recorded as the relevant threshold. It can be understood that all target coefficients have corresponding relevant thresholds. For example, the β-CD encapsulation molar ratio is positively correlated with the EGCG purity value. Furthermore, the positive correlation between the β-CD encapsulation molar ratio and the EGCG purity value is expressed through a weighting formula. The value of the weighting coefficient can be determined based on the user's historical experience and the degree of influence of the EGCG purity value on the encapsulation effect. In addition, the value of the weighting coefficient can be optimized by combining the historical records of multiple embryonic capsule preparation processes containing tea polyphenols with multilayer perceptron. The optimization of the weighting coefficient using multilayer perceptron is something that is easy for those skilled in the art to understand, and will not be elaborated here. The principle of determining the weighting coefficients corresponding to other target coefficients and relevant thresholds is the same, and will not be elaborated here.

[0049] Specifically, it also includes:

[0050] Based on the state of the second capsule, the optimized analysis method was determined to be preparation modification optimization.

[0051] The method of change is determined based on the abnormality of embryonic activity, which involves adjusting the embedding temperature or drying time.

[0052] Specifically, in this embodiment of the invention, the β-CD encapsulation molar ratio is determined based on the EGCG purity value;

[0053] The β-CD encapsulation molar ratio is positively correlated with the EGCG purity value.

[0054] Among them, the EGCG purity value is the mass percentage of epigallocatechin gallate (EGCG) in tea polyphenols. The EGCG purity value is determined by high performance liquid chromatography. High-purity EGCG can improve encapsulation efficiency and capsule stability. The β-CD encapsulation molar ratio is the molar ratio of β-cyclodextrin to tea polyphenols. It is initially calculated by a preset ratio and then adjusted based on the turbidity change rate and pH shift of the encapsulation reaction solution to optimize the encapsulation effect.

[0055] Please see Figure 2As shown, it is a flowchart of adjusting the β-cyclodextrin encapsulation molar ratio at abnormal reaction process nodes according to an embodiment of the present invention.

[0056] Specifically, embodiments of the present invention adjust the β-cyclodextrin encapsulation molar ratio at abnormal reaction process nodes based on turbidity change rate and pH shift, including:

[0057] For a single abnormal response process node:

[0058] If the turbidity change rate is greater than or equal to the preset turbidity change rate or the pH shift is greater than or equal to the preset pH shift, then the β-cyclodextrin encapsulation molar ratio will be reduced.

[0059] If the turbidity change rate is less than the preset turbidity change rate and the pH shift is less than the preset pH shift, then the β-cyclodextrin encapsulation molar ratio will be increased.

[0060] The abnormal reaction process node is the reaction process node whose evaluation deviation value is greater than the preset evaluation deviation value.

[0061] Specifically, this invention optimizes the stability of the tea polyphenol-embryoside complex by dynamically adjusting the β-cyclodextrin encapsulation molar ratio, monitors the encapsulation reaction process in real time using turbidity change rate and pH shift, dynamically adjusts the encapsulation ratio for abnormal nodes to improve encapsulation efficiency, increases the loading rate of active ingredients and anti-degradation ability, improves the accuracy of encapsulation anomaly detection, reduces batch-to-batch quality fluctuations, enhances the sustained-release characteristics of embryoside, and reduces the risk of activity loss.

[0062] In this invention, the reaction process nodes are set by the user. A method for setting reaction process nodes is provided: taking the moment when tea polyphenols and β-cyclodextrin begin to mix as the starting point, a reaction process node is set every certain degree of reaction according to the reaction process sequence, for example, when the conversion rate increases by 5%.

[0063] For a single reaction process node, the reaction process node is designated as the target reaction process node. The reaction process node that is adjacent to the target reaction process node and located before the target reaction process node is designated as the neighboring reaction process node. If there are no other reaction process nodes before the target reaction process node, the starting point is designated as the neighboring reaction process node.

[0064] The turbidity change rate corresponding to the target reaction process node is the ratio of the difference between the turbidity of the reaction liquid corresponding to the neighboring reaction process node and the turbidity of the reaction liquid corresponding to the target reaction process node to the turbidity of the reaction liquid corresponding to the neighboring reaction process node. The turbidity change rate reflects the rate of change of the turbidity of the system during the encapsulation process. Too high a rate may mean incomplete encapsulation or particle agglomeration, while too low a rate indicates that the encapsulation reaction is slow.

[0065] The pH offset corresponding to the target reaction process node is the difference between the pH value of the reaction solution at the target reaction process node and the initial pH value of the reaction solution. The pH offset reflects the change in the acidity and alkalinity of the system during the encapsulation reaction. Deviation from the preset range may affect the encapsulation effect of β-CD and tea polyphenols.

[0066] The evaluation threshold corresponding to the target reaction process node is the ratio of the turbidity change rate corresponding to the target reaction process node to the preset turbidity change rate, plus the ratio of the pH offset corresponding to the target reaction process node to the preset pH offset.

[0067] The evaluation deviation value is the absolute value of the difference between the evaluation threshold corresponding to the current preparation process and the average value of the evaluation thresholds corresponding to historical records that can meet user needs.

[0068] The increase or decrease in the β-CD encapsulation molar ratio corresponding to a single reaction process node is positively correlated with the evaluation deviation value corresponding to that reaction process node.

[0069] Users can determine the preset turbidity change rate and preset pH offset values ​​according to the actual application scenario. The smaller the preset turbidity change rate and preset pH offset values, the greater the user's need to reduce the β-CD encapsulation molar ratio. A method for determining the preset turbidity change rate and preset pH offset values ​​is provided, which detects the historical records of the user's reduction of the β-CD encapsulation molar ratio, and records the average turbidity change rate corresponding to the historical records that meet the user's needs as the preset turbidity change rate, and records the average pH offset corresponding to the historical records that meet the user's needs as the preset pH offset.

[0070] The preset evaluation deviation value can be determined by the user based on the actual application scenario. The greater the user's need to improve embedding efficiency, the smaller the preset evaluation deviation value should be. A method for determining the preset evaluation deviation value is provided, which is the average of the evaluation deviation values ​​corresponding to each abnormal response process node in the historical record that can meet the user's needs.

[0071] Specifically, in this embodiment of the invention, the concentration of wet granulation binder is determined based on the activity sensitivity coefficient of embryonic factor;

[0072] The concentration of the adhesive is positively correlated with the activity sensitivity coefficient of the embryonic factor.

[0073] The activity sensitivity coefficient of embryonic extract is the ratio of the viscosity change rate of embryonic extract at a set temperature to the viscosity change rate at a standard temperature, reflecting the activity retention characteristics of embryonic extract. The higher the activity sensitivity coefficient, the more appropriate the binder concentration needs to be to enhance the granule formability. The binder concentration is the percentage of the mass of binder added during wet granulation to the dry granules. It is adjusted by combining the initial preset value with the activity sensitivity coefficient to ensure that the granules have good plasticity and flowability. The binder is hydroxypropyl methylcellulose.

[0074] Specifically, in this embodiment of the invention, granulated soft material is prepared under wet granulation conditions.

[0075] Please see Figure 3 As shown, it is a flowchart for determining the adjustment of the adhesive addition rate in an embodiment of the present invention.

[0076] Specifically, in this embodiment of the invention, the adhesive addition rate is adjusted according to the torque endpoint value and particle size distribution dispersion of the granulated soft material;

[0077] If the torque endpoint value is less than the preset torque endpoint value or the particle size distribution dispersion is greater than or equal to the preset particle size distribution dispersion, then increase the adhesive addition rate.

[0078] If the torque endpoint value is greater than or equal to the preset torque endpoint value and the particle size distribution dispersion is less than the preset particle size distribution dispersion, then reduce the adhesive addition rate.

[0079] The preset torque endpoint value and preset particle size distribution dispersion values ​​are determined based on historical qualified records to ensure stable particle quality.

[0080] Specifically, this invention improves the adaptability of the granulation process by dynamically adjusting the addition rate of the binder during wet granulation by real-time monitoring of the torque endpoint value and particle size distribution dispersion of the granulated soft material, reducing the failure rate of subsequent filling processes due to particle quality fluctuations, and improving batch consistency, thereby enhancing the stability of the embryonic capsule preparation process.

[0081] The torque endpoint value of the granulated soft material is the value when the torque reaches a stable state during the mixing process of the granulator, reflecting the uniformity of material mixing and the hardness of the soft material; the particle size distribution dispersion is determined by laser diffraction, which characterizes the uniformity of particle size.

[0082] Specifically, in this embodiment of the invention, the dry granules are obtained by drying and sieving the granulated soft material.

[0083] Specifically, the mesh size of the granulation screen is determined based on the moisture gradient difference of the granulation material;

[0084] The moisture gradient difference is the difference in moisture content between different locations of the granulated material, such as the center and the surface, which is measured by a near-infrared moisture meter. The larger the moisture gradient difference, the greater the internal stress of the granulated material, requiring the selection of a finer sieve, i.e., a larger mesh size, to further granulate and reduce the non-uniformity of the granulated material. The mesh size of the granulation sieve is positively correlated with the moisture gradient difference, and the specific value is verified through experiments to ensure uniform moisture content of the dry granules.

[0085] Specifically, in this embodiment of the invention, the parameters of the capsule filling machine are determined based on the angle of repose and bulk density of the dry particles;

[0086] The angle of repose is the cone angle formed by dry particles falling freely from a certain height and accumulating. It reflects the flowability of the particles. The smaller the angle of repose, the better the flowability, and the rotation speed of the filling machine can be appropriately increased. The bulk density is the packing density of dry particles in a loose state. It reflects the porosity between particles. The larger the bulk density, the higher the filling capacity per unit volume, and the filling depth of the filling machine can be appropriately increased. The filling machine parameters (such as rotation speed and filling depth) are correlated with the angle of repose and bulk density through empirical formulas or experimental calibration to achieve accurate filling.

[0087] Specifically, in this embodiment of the invention, the capsule state is determined based on the dissolution deviation value and the capsule shell integrity index after filling;

[0088] The first capsule state is characterized by a dissolution deviation value greater than or equal to a preset dissolution deviation value and a capsule shell integrity index greater than or equal to a preset capsule shell integrity index.

[0089] The second capsule state is characterized by a dissolution deviation value that is less than the preset dissolution deviation value but a capsule shell integrity index that is less than the preset capsule shell integrity index.

[0090] The third capsule state is defined as follows: the dissolution deviation value is less than the preset dissolution deviation value and the capsule shell integrity index is greater than or equal to the preset capsule shell integrity index.

[0091] Dissolution deviation is the difference between the measured dissolution amount and the target dissolution amount, reflecting the release performance of the active ingredients in the capsule; the capsule shell integrity index is the ratio of the number of intact capsules to the total number of capsules, reflecting the sealing performance of the capsule shell.

[0092] Specifically, if the capsule is in the first capsule state, the optimization analysis method is stability optimization; if the capsule is in the second capsule state, the optimization analysis method is preparation change optimization; if the capsule is in the third capsule state, the overall performance of the target capsule meets the standard and no adjustment is required.

[0093] Specifically, this invention determines the product quality status by monitoring the dissolution deviation value and shell integrity index of the filled capsules. For the first state where the dissolution performance is abnormal but the shell is well sealed, the drying time is adjusted. For the second state where the dissolution is qualified but the shell is damaged, the embedding temperature is adjusted. This avoids the one-sidedness of evaluation by a single indicator, improves production efficiency, enhances the adaptability of the production system to raw material fluctuations through dynamic adjustment of the preparation process, and reduces the risk of microbial invasion through real-time monitoring, thereby improving the stability of the embryonic capsule preparation process.

[0094] Dissolution testing was performed on the filled capsules using a dissolution tester. A paddle method was used with a 900 mL medium of pH 6.8 phosphate buffer, a temperature of 37±0.5℃, a rotation speed of 50 rpm, and a sampling time of 15 min. The dissolution reference value was the amount of dissolution at the first sampling time point, and the performance change value was the difference between the amount of dissolution at the first and last sampling time points. The preset dissolution deviation value and preset capsule shell integrity index were determined by the user according to their own indicators. The smaller the value, the higher the performance requirements of the capsules.

[0095] Please see Figure 4 As shown, it is a flowchart of determining the optimization method in an embodiment of the present invention.

[0096] Specifically, in this embodiment of the invention, under the condition of determining the capsule state, the optimization method is determined based on the comparison result of the abnormality of embryonic activity of the corresponding capsule state and the preset abnormality of embryonic activity.

[0097] If the abnormality of embryonic activity is less than or equal to the preset abnormality of embryonic activity, then the drying time is adjusted.

[0098] If the abnormality of embryonic activity is greater than the preset abnormality of embryonic activity, then the embedding temperature is adjusted.

[0099] Specifically, this invention, after determining the capsule state, selects and optimizes the drying time or embedding temperature based on the abnormality of embryonic protein activity, thereby achieving precise process intervention, improving the bioactivity of embryonic protein, reducing the damage of high temperature to the embryonic protein structure, shortening the response cycle of quality abnormalities, and thus improving the stability of the embryonic protein capsule preparation process.

[0100] In this embodiment of the invention, the abnormality of embryonic activity is the percentage deviation between the measured embryonic activity and the target activity. The calculation formula is the absolute value of the ratio of the difference between the measured embryonic activity and the target activity to the target activity. The measured activity is determined by bioactivity testing, such as enzyme-linked immunosorbent assay (ELISA), to measure the activity value of embryonic activity in the filled capsule. The test is conducted at a standard temperature (25°C) to eliminate external interference. The target activity is the expected activity value set based on user requirements or historical qualified records. The target activity is predefined by the user according to self-defined indicators.

[0101] The preset embryonic activity anomaly level is determined by the user based on historical records. The average value of the embryonic activity anomaly level is extracted from the historical records marked as "meets user requirements" as the preset embryonic activity anomaly level. For example, if the average preset embryonic activity anomaly level of qualified samples in the historical records is 5%, then the preset embryonic activity anomaly level is set to 5%. Users can adjust this threshold according to their own set indicators. The smaller the threshold, the higher the requirement for activity stability.

[0102] The embryonic protein activity retention rate was close to the target value, indicating low anomaly. However, the capsules exhibited dissolution deviations or insufficient shell integrity. Extending the drying time further reduced the moisture content of the dry granules, improving the shell sealing. Simultaneously, optimizing the granule compaction improved dissolution performance, shortened the drying time, and prevented over-drying that could lead to excessively hard granules, thus improving the flowability and filling uniformity of the dry granules. The embryonic protein activity retention rate was significantly lower than the target value, indicating high anomaly. Lowering the encapsulation temperature reduced the thermal damage to the embryonic protein caused by high temperatures. At the same time, the inclusion efficiency of β-cyclodextrin and tea polyphenols was optimized.

[0103] The capsule prepared by optimizing the relevant parameters of the target capsule preparation process through optimization analysis is denoted as embryonic capsule.

[0104] The technical solution of the present invention has been described above with reference to the preferred embodiments shown in the accompanying drawings. However, it will be readily understood by those skilled in the art that the scope of protection of the present invention is obviously not limited to these specific embodiments. Without departing from the principles of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will all fall within the scope of protection of the present invention.

[0105] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A process for preparing embryonic capsules containing tea polyphenols, characterized in that, include: Weigh out tea polyphenols, β-cyclodextrin and embryonic extract according to a preset ratio; The β-cyclodextrin encapsulation molar ratio was determined based on the EGCG purity value of the tea polyphenols. The tea polyphenols, the β-cyclodextrin and the embryonic extract were encapsulated to obtain an encapsulation reaction solution. The encapsulation molar ratio was adjusted according to the turbidity change rate and pH shift of the encapsulation reaction solution. The concentration of wet granulation binder is determined based on the activity sensitivity coefficient of the embryonic extract for wet granulation, and the binder addition rate is adjusted based on the torque endpoint value and particle size distribution dispersion of the granulated soft material obtained by wet granulation. The dry granules obtained after drying and sieving the granulated soft material are filled into the capsule shell to obtain the target capsule. The capsule state is determined based on the dissolution deviation value and capsule shell integrity index of the target capsule. The optimization method is determined based on the abnormality of embryonic activity of the corresponding capsule state, which is to adjust and optimize the drying time or encapsulation temperature. The embryonic capsules were obtained after adjustment and optimization.

2. The preparation process of embryonic capsules containing tea polyphenols according to claim 1, characterized in that, The β-cyclodextrin encapsulation molar ratio was determined based on the EGCG purity value of the tea polyphenols. The β-cyclodextrin encapsulation molar ratio is positively correlated with the EGCG purity value.

3. The preparation process of embryonic capsules containing tea polyphenols according to claim 2, characterized in that, The β-cyclodextrin encapsulation molar ratio at abnormal reaction process nodes is adjusted based on the turbidity change rate and pH shift of the encapsulation reaction solution. The adjustment of the β-cyclodextrin encapsulation molar ratio at a single abnormal reaction process node includes: If the comparison results show that the turbidity change rate is greater than or equal to the preset turbidity change rate or the pH shift is greater than or equal to the preset pH shift, the β-cyclodextrin encapsulation molar ratio is reduced. If the comparison results show that the turbidity change rate is less than the preset turbidity change rate and the pH shift is less than the preset pH shift, the β-cyclodextrin encapsulation molar ratio should be increased. The abnormal reaction process node is the reaction process node whose evaluation deviation value is greater than the preset evaluation deviation value.

4. The preparation process of embryonic capsules containing tea polyphenols according to claim 3, characterized in that, The concentration of wet granulation binder is determined based on the activity sensitivity coefficient of the embryonic factor; The concentration of the adhesive is positively correlated with the activity sensitivity coefficient of the embryonic factor.

5. The preparation process of embryonic capsules containing tea polyphenols according to claim 4, characterized in that, The adhesive addition rate is increased based on the comparison results of the torque endpoint value of the granulated soft material being less than the preset torque endpoint value or the particle size distribution dispersion being greater than or equal to the preset particle size distribution dispersion.

6. The preparation process of embryonic capsules containing tea polyphenols according to claim 5, characterized in that, The adhesive addition rate is reduced based on the comparison results where the torque endpoint value of the granulated soft material is greater than or equal to the preset torque endpoint value and the particle size distribution dispersion is less than the preset particle size distribution dispersion.

7. The preparation process of embryonic capsules containing tea polyphenols according to claim 6, characterized in that, Based on the comparison results that the dissolution deviation value of the filled capsule is greater than or equal to the preset dissolution deviation value and the capsule shell integrity index is greater than or equal to the preset capsule shell integrity index, the embryonic capsule is determined to be in the first capsule state.

8. The preparation process of embryonic capsules containing tea polyphenols according to claim 7, characterized in that, Based on the comparison results that the dissolution deviation value of the filled capsule is less than the preset dissolution deviation value, but the capsule shell integrity index is less than the preset capsule shell integrity index, the embryonic capsule is determined to be in the second capsule state.

9. The preparation process of embryonic capsules containing tea polyphenols according to claim 8, characterized in that, The drying time is adjusted based on the comparison results of the embryonic activity abnormality degree of the corresponding capsule state being less than or equal to the preset embryonic activity abnormality degree.

10. The preparation process of embryonic capsules containing tea polyphenols according to claim 9, characterized in that, The embedding temperature is adjusted based on the comparison results of the embryonic activity abnormality degree of the corresponding capsule state being greater than the preset embryonic activity abnormality degree.

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