Nano-encapsulated targeted active ingredients from medicinal plants

Abstract

The application relates to the technical field of plant functional component extraction, in particular to a medicinal plant functional component nano-coating targeted essence extraction process, which comprises the following steps: medicinal material pretreatment; solvent selection and extraction system construction; nano-coating material screening and nano-coating system construction; specifically, extracting the extract of a plurality of insoluble components in filtrate, so as to use the mass and HLB value of the extract as the satisfaction condition for constructing different assistant ratios of the nano-coating material; using a response surface method to obtain optimal temperature, PH value and rotating speed parameters for constructing the nano-coating system under different assistant ratios, and based on the optimal parameters, an automatic control system is used to realize real-time control of temperature and rotating speed in the nano-coating system construction process; separation, purification and impurity removal; concentration and stability regulation. The application aims to improve the efficiency and stability of the nano-coating targeted extraction process for extracting medicinal plant functional components.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of plant functional ingredient extraction, in particular to a nano-encapsulated targeted essence extraction process of medicinal plant functional ingredients. BACKGROUND

[0002] The medicinal plant functional ingredients refer to a mixture of one or several chemical components in medicinal plants with certain pharmacological functions, such as flavonoids, polysaccharides and total saponins; they have the characteristics of multi-component synergy, natural combination retention and stable quality control indicators; and they are widely used in the fields of modernization of traditional Chinese medicine preparations and functional foods or health products. The medicinal plant ingredients are mainly divided into primary metabolites and secondary metabolites, wherein the primary metabolites include sugars, proteins, fats, vitamins and cellulose; the secondary metabolites include flavones and their glycosides, terpenes and their glycosides, steroids and their glycosides, alkaloids, quinone compounds and others; the traditional methods usually extract the functional ingredients by decoction, immersion, percolation, distillation and reflux extraction, but have the disadvantages of low efficiency, insufficient purity, high energy consumption, serious component destruction and incomplete functional ingredients; and the modern extraction processes, such as supercritical extraction, ultrasonic-assisted extraction, microwave-assisted extraction and membrane separation technology, have the problems of insufficient technical adaptability, limited economy and scale, difficult quality control and low environmental protection and safety.

[0003] Based on the above-mentioned problems of low extraction efficiency and stability of plant functional ingredients, the nano-encapsulation technology can use surfactants and amphiphilic polymers to encapsulate specific substances inside or on the surface of nanoscale carriers under certain conditions; and the nano-encapsulation can change the physicochemical properties, stability, solubility and bioavailability of the encapsulated substances, realize the targeted delivery and controlled release of the encapsulated substances; therefore, the application of nano-encapsulation technology to the extraction of plant functional ingredients can effectively improve the extraction efficiency and stability of the ingredients, but the selection of solvents and amphiphilic substances, the quality ratio and the construction of nano-encapsulation system have a great influence on the accuracy of the capture of functional ingredients; if the solvents and amphiphilic substances selected for the extraction of different ingredients have large deviations, and the stability is low during the system construction process, the accuracy of the nano-encapsulation technology-based extraction of medicinal plant functional ingredients may be reduced. SUMMARY

[0004] In order to solve the above technical problems, the present application provides a nano-encapsulated targeted essence extraction process of medicinal plant functional ingredients to solve the existing problems.

[0005] The nano-encapsulated targeted essence extraction process of medicinal plant functional ingredients of the present application adopts the following technical scheme:

[0006] An embodiment of the present application provides a nano-encapsulated targeted refined extraction process of medicinal plant functional components, which comprises the following steps:

[0007] S1: pretreatment of medicinal materials: screening, cleaning and crushing of raw materials of medicinal plants to obtain plant raw material particles;

[0008] S2: selection of solvent and construction of extraction system: selecting a solvent to extract a filtrate containing functional components from the plant raw material particles;

[0009] S3: selection of nano-encapsulated material and construction of nano-encapsulation system; specifically:

[0010] (1) extracting the extract of several insoluble components in the filtrate to use the mass and HLB value of the extract as a satisfaction condition for constructing different assistant ratios of nano-encapsulated material;

[0011] (2) using the response surface method to obtain the optimal temperature, PH value and rotation speed parameters for constructing the nano-encapsulation system under different assistant ratios, and based on the optimal parameters, the temperature and rotation speed are controlled in real time during the construction of the nano-encapsulation system by using an automatic control system;

[0012] S4: separation, purification and impurity removal: centrifuging and filtering the mixed solution after the filtrate is encapsulated by the nano-encapsulated material constructed in step S3 to obtain a clear filtrate containing nano-encapsulated complexes;

[0013] S5: concentration and stability regulation: concentrating the clear filtrate in a rotary evaporator to determine whether to adjust the ratio.

[0014] Preferably, the solvent is 70-75% ethanol; the mass-volume ratio of the mixed plant raw material particles to the solvent is 1:8-1:12.

[0015] Preferably, the specific process in (1) is:

[0016] The total mass is obtained by drying and weighing a preset volume of filtrate;

[0017] The weight of the petroleum ether extract is obtained by adding the dried extract to petroleum ether for extraction and drying;

[0018] The mass of the ethanol-soluble substance is obtained by drying the residue after extraction of the petroleum ether extract and adding a preset concentration of ethanol for extraction;

[0019] The average HLB value of the mass and HLB value of the petroleum ether extract and the ethanol-soluble substance is calculated as the theoretical HLB value of all insoluble components;

[0020] The amount of the amphiphilic substance added is calculated by the total mass, the petroleum ether extract, and the ethanol soluble substance;

[0021] The mass and the average HLB value of the screened amphiphilic substance for constructing the nano-encapsulated material meet two conditions of the added amount and the theoretical HLB value.

[0022] Preferably, the amphiphilic substance for constructing the nano-encapsulated material includes, but is not limited to, single and double glycerol fatty acid esters, Tween 80, phospholipids, polyethylene glycol, and 2-3 kinds of auxiliary agents in glycerol.

[0023] Preferably, the calculation method of the added amount of the amphiphilic substance is:

[0024]

[0025] wherein, m 总 represents the added amount of the amphiphilic substance; M 总 represents the total mass of the extract after drying the filtrate; M1 and M2 respectively represent the mass of the petroleum ether extract and the ethanol extract, i.e., the mass of all insoluble substances in the obtained extract.

[0026] Preferably, the real-time control of the temperature and the rotating speed in the nano-encapsulated system construction process based on the optimal parameters combined with the automatic control system includes:

[0027] The time length of the nano-encapsulated system construction process is set with monitoring points at equal time intervals;

[0028] The two kinds of monitoring data collected up to the current monitoring point are respectively arranged in time sequence to calculate the difference between each element in the time sequence and the preset value of the corresponding monitoring parameter, and the ratio of the difference to the preset value is taken as the fluctuation deviation of the current monitoring point; the DTW distance is calculated as the characteristic difference value of the fluctuation deviation of the current monitoring point after the corresponding fluctuation deviations between the two kinds of monitoring data are sorted in time sequence;

[0029] The trend statistic of all fluctuation deviations of each kind of monitoring data collected at the current monitoring point is calculated by using the MK trend checking algorithm, and the mean value of the trend statistics corresponding to the two kinds of monitoring data is taken as the characteristic value of the fluctuation trend change of the current monitoring point;

[0030] The characteristic coefficient of the nano-encapsulated system construction control response at the current monitoring point in the control process is calculated by using the characteristic difference value and the characteristic value of the fluctuation trend change of the current monitoring point;

[0031] The mean value of the difference between all monitoring data collected up to the current monitoring point and the preset value of the corresponding monitoring parameter is taken as the characteristic value of the cumulative control deviation at the current monitoring point in the control process.

[0032] calculating an adjustment coefficient of the feedback correction deviation at the current monitoring point in the control process based on the characteristic coefficient of the nano-encapsulated system construction control response at the current monitoring point in the control process and the characteristic value of the cumulative control deviation at the current monitoring point;

[0033] adjusting the value of the feedback deviation calculated at the current monitoring point in the control process by using the normalized value of the adjustment coefficient, so as to optimize and adjust the feedback error of the real-time control at the current monitoring point.

[0034] Preferably, the calculation method of the characteristic coefficient of the nano-encapsulated system construction control response at the current monitoring point in the control process is as follows: x = a x × b x ; wherein h x represents the characteristic coefficient of the nano-encapsulated system construction control response at the xth monitoring point in the control process; a x represents the characteristic difference value of the fluctuation deviation at the xth monitoring point in the control process; and b x represents the characteristic value of the fluctuation trend change at the xth monitoring point in the control process.

[0035] Preferably, the calculation method of the adjustment coefficient of the feedback correction deviation at the current monitoring point in the control process is as follows:

[0036]

[0037] wherein k x represents the adjustment coefficient of the feedback correction deviation at the xth monitoring point in the control process; n represents the number of monitoring points passed until the time point at which the current monitoring point is located; μ x,i represents the absolute value of the difference between the characteristic values of the cumulative control deviations at the xth and ith monitoring points in the control process; h x,i represents the absolute value of the difference between the characteristic coefficients of the nano-encapsulated system construction control responses at the xth and ith monitoring points in the control process.

[0038] Preferably, the adjustment of the value of the feedback deviation calculated at the current monitoring point in the control process by using the normalized value of the adjustment coefficient comprises:

[0039]

[0040] wherein σ is the value of the adjusted feedback deviation at the xth monitoring point in the control process; σ0 is the value of the feedback deviation calculated at the xth monitoring point in the control process, which is determined by the difference between each kind of monitoring data collected at the xth monitoring point and the preset value of the corresponding monitoring parameter; and τ is the preset threshold value of the feedback correction adjustment.

[0041] Preferably, the concentration conditions are 45-50℃, 0.08-0.09 MPa in a rotary evaporator until the solid content in the clear filtrate reaches 20-30%.

[0042] In the above scheme, the beneficial effects are that, considering the problems of low extraction efficiency and low stability of ingredients in traditional plant efficacy ingredient extraction methods, the application proposes a medicinal plant efficacy ingredient nano-coated targeted extraction process. The efficacy ingredients in medicinal plants are extracted by using nano-coating technology. First, the medicinal plant raw materials of different prescriptions are pretreated, and the selection of amphiphilic substances is based on the ingredients of the medicinal plant raw materials. The optimal mass ratio of the selected amphiphilic substances is dynamically determined based on the calculation results of the theoretical HLB value and the amount of amphiphilic substances in the filtrate after extraction of the medicinal plant raw materials. Further, to improve the extraction efficiency of nano-coating, the optimal parameters for constructing the nano-coating system under the mass ratio are determined by the response surface method, and the control optimization of the system construction is combined with the monitoring data in the real-time construction process. The beneficial effects are that the extraction of different medicinal plant efficacy ingredients is faced, the dynamic determination of amphiphilic substances and mass ratio is realized for efficient nano-coating targeted extraction, and on this basis, the accurate parameter setting and stability control of the nano-coating system construction are realized, which effectively improves the efficiency and stability of the nano-coating targeted extraction process for the extraction of medicinal plant efficacy ingredients. BRIEF DESCRIPTION OF DRAWINGS

[0043] In order to more clearly illustrate the technical solutions and advantages in the embodiments of the application or prior art, the drawings needed to be used in the embodiments or prior art description will be briefly introduced. Obviously, the drawings in the following description are only some embodiments of the application, and those skilled in the art can also obtain other drawings according to these drawings without creating any creative labor.

[0044] Figure 1 The step flow chart of the medicinal plant efficacy ingredient nano-coated targeted extraction process provided by an embodiment of the application. DETAILED DESCRIPTION

[0045] In order to further illustrate the technical means and effects adopted by the application to achieve the predetermined invention purpose, the medicinal plant efficacy ingredient nano-coated targeted extraction process according to the application is described in detail below in combination with the drawings and preferred embodiments. The specific implementation, structure, features and effects of the medicinal plant efficacy ingredient nano-coated targeted extraction process are described in detail as follows. In the following description, different "one embodiment" or "another embodiment" do not necessarily refer to the same embodiment. In addition, the specific features, structures or characteristics in one or more embodiments can be combined in any suitable form.

[0046] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

[0047] The specific scheme of the medicinal plant efficacy component nano-encapsulated targeted extraction process provided by the present application is described below in detail with reference to the accompanying drawings.

[0048] The medicinal plant efficacy component nano-encapsulated targeted extraction process provided by one embodiment of the present application has a preparation flowchart as shown in Figure 1 , and the specific preparation process is as follows:

[0049] S1: Pretreatment of medicinal materials: screening, cleaning and crushing of raw materials of medicinal plants to obtain plant raw material particles.

[0050] In the present application, different medicinal plant raw materials are treated; specifically, different medicinal parts of plants contain different efficacy components, and before extracting the efficacy components of plants, the raw materials of medicinal plants need to be screened and cleaned first to remove mud, impurities and non-medicinal parts; after cleaning, the medicinal plants are crushed, and after crushing, the vibration screen with 20-40 meshes is used for screening to obtain uniform plant raw material particles, which increases the contact area between the plant raw material and the solvent and improves the extraction efficiency.

[0051] For example, for hard medicinal materials such as lotus leaves and hawthorn, the solvent can penetrate the plant cells after crushing; and for seeds or fungi such as Chinese date kernel and ganoderma, the hard seed coat or cell wall can be broken after crushing, which is beneficial to the release of efficacy components.

[0052] S2: Selection of solvent and construction of extraction system: selection of solvent to extract filtrate containing efficacy components from plant raw material particles.

[0053] Ethanol has high polarity and can efficiently dissolve most of the lipid-soluble and moderately polar efficacy components of flavonoids, saponins and alkaloids, and has strong penetration of plant cell membranes, which can promote the release of intracellular components; therefore, 70-75% ethanol is used as the medium for extraction of plant efficacy components in this embodiment, which can avoid the dissolution of protein, starch and fat molecules and other impurities in plant cells, thereby reducing the dissolution of ineffective components.

[0054] Further, the crushed plant raw material particles are mixed with the solvent in a mass-volume ratio of 1:8 to 1:12, mixed and soaked at room temperature for 30 min, and after soaking, stirred in a constant temperature water bath at 50 to 60°C for 12 h, and in the process of extraction, the solvent and the medicinal material are fully mixed and contacted by stirring at a speed of 100 to 150 r / min. After extraction, the filtrate containing the effective components of the medicinal plant is collected through a Buchner funnel, and the dregs are preserved for subsequent use as raw materials for feed.

[0055] S3, nano-encapsulated material screening and nano-encapsulated system construction;

[0056] In the process of targeted extraction of plant effective components by nano-encapsulation technology, appropriate lipophilic substances are selected for the construction of nano-microspheres according to the properties of the effective components in the filtrate of the extracted plant raw material.

[0057] Since different medicinal parts (roots, stems, leaves, flowers, fruits, seeds) of plants contain different effective components (flavonoids, polysaccharides, triterpenes, saponins, etc.), according to the physicochemical properties of medicinal plants and the target substances to be extracted, nano-encapsulated material (for example, amphiphilic substances) is selected for different target extracts, and different combinations and ratios of additives are used to construct nano-encapsulated material, for example, amphiphilic substances include: single and double glycerol fatty acid esters, Tween 80, phospholipids, polyethylene glycol, glycerol, etc.

[0058] Among them, the constructed nano-microspheres need to have both hydrophilic groups and hydrophobic groups, and can self-assemble to form nano-microspheres with "hydrophilic outer layer and hydrophobic inner core", that is, the hydrophobic inner core of the nano-microspheres encapsulates the fat-soluble effective components through hydrophobic interaction, and the hydrophilic outer layer keeps the nano-microspheres stable in ethanol solution; The specific process of nano-encapsulated material screening and nano-encapsulated system construction is as follows:

[0059] (1) The extract of several insoluble components in the filtrate is extracted, and the mass and HLB value of the extract are used as the satisfaction condition for different additive ratios for constructing nano-encapsulated material.

[0060] First, the components in the filtrate are determined, and the ratio of the selected amphiphilic substances is calculated based on the determination results. The specific selection and ratio determination process is as follows:

[0061] Specifically, in an embodiment of the present application, 50 ml of filtrate is dried, weighed after drying, and the total mass M of the extract after drying of the filtrate is obtained 总; the extract after drying is added to petroleum ether for extraction, and after filtration, the extract of the extract is obtained by using the extract of the extract, and the mass of the petroleum ether extract is obtained by drying the extract of the extract, and the mass of the petroleum ether extract is obtained by calculating the mass difference of the extract of the extract by evaporating the solvent; the filter residue after the extraction of the petroleum ether extract is dried, and 95% ethanol is added for extraction, and after filtration, the mass M2 of the ethanol extract is obtained by using the extract of the extract; further, according to the literature, the HLB values of different insoluble components are calculated, and the theoretical HLB values of all insoluble components are calculated, and the calculation relationship is as follows:

[0062]

[0063] Among them, HLB represents the theoretical HLB value of all insoluble components, M1 and HLB1 represent the mass and theoretical HLB value of the petroleum ether extract respectively; M2 and HLB2 represent the mass and theoretical HLB value of the ethanol extract respectively; it should be noted that the extraction calculation in the present application is directed to known medicinal formulations, so the components in the petroleum ether extract and the 95% ethanol extract are known.

[0064] Further, based on the mass of the insoluble components in the filtrate and the total mass of the extract, the addition amount of the amphiphilic substance for nano-encapsulation extraction is calculated, and the calculation relationship is as follows:

[0065]

[0066] Among them, m 总 represents the addition amount of the amphiphilic substance; M 总 represents the total mass of the extract after drying the filtrate; M1 and M2 represent the mass of the petroleum ether extract and the ethanol extract respectively, i.e. the mass of all insoluble components in the obtained extract.

[0067] Based on the above calculation, the theoretical HLB value of all insoluble components in the extract and the addition amount of the amphiphilic substance can be obtained, and the ratio of the amphiphilic substance is further calculated based on the obtained mass.

[0068] Specifically, in the present embodiment, the prescriptions used in the specific implementation process include but are not limited to the following: the prescription of the meal shape, the prescription of the mind, the prescription of the lipid and the wing dream an, and the amphiphilic substances used include but are not limited to the following: water-soluble mono-diglyceride fatty acid ester, soybean lecithin and glycerol.

[0069] Based on the theoretical HLB values of the above three amphiphilic substances, HLB3, HLB4 and HLB5 are respectively obtained, and the corresponding masses are m3, m4 and m5 respectively; in order to basically meet the balance of the amphiphilic characteristics of the effective components in the extract, the mass of the amphiphilic substance should satisfy the following formula:

[0070] m 总= m3 + m4 + m5

[0071]

[0072] In the above formula, m 总 represents the amount of the added amphiphilic substance; HLB represents the theoretical HLB value of all insoluble components; the mass of the amphiphilic substance can be determined by the above formula to meet the basic encapsulation requirements.

[0073] It should be noted that the theoretical HLB value needs to be further adjusted through experiments on the basis of meeting the basic encapsulation requirements, and then the appropriate ratio of the amphiphilic substance is selected to improve the encapsulation effect.

[0074] Specifically, the ratio of different HLB values can be obtained by adjusting the mass by the above formula, and the state of the extraction liquid is observed after adding the amphiphilic substance to determine the final mass ratio.

[0075] For example, the theoretical HLB value of Zhanxing Decoction calculated based on the above formula is 9.99, and on the basis of meeting the requirement of 9.99, experiments are conducted by adjusting the mass ratio, and it is found that when HLB is 14, the extraction liquid is uniform and transparent, and there is no precipitation of insoluble substances.

[0076] (2) The optimal temperature, pH value and rotation speed parameters for constructing the nano-encapsulation system under different ratios of the auxiliary agent are obtained by using the response surface method, and the temperature and rotation speed are controlled in real time during the construction of the nano-encapsulation system based on the optimal parameters and the automatic control system.

[0077] First, to construct the nano-encapsulation particles for precise extraction of the efficacy components under the ratio of the selected amphiphilic substance meeting the above conditions, the response surface method is used to determine the optimal parameter settings for stable construction of the nano-particles.

[0078] Specifically, temperature, pH value and rotation speed are input as independent variables, wherein the temperature range is 40-60℃, the pH value range is 5-7, and the rotation speed is 100-300 r / min; the encapsulation efficiency is taken as the response value, wherein the encapsulation efficiency is determined by high-speed centrifugation; based on the historical data of nano-encapsulation extraction of the same plant material, the Design Expert software is used for multiple regression analysis to obtain the optimal parameters of the current plant material under the above ratio. The process of obtaining the optimal temperature, pH value and rotation speed by the response surface method is well known to those skilled in the art, and will not be described here.

[0079] Further, the selected amphiphilic substances are added to the obtained filtrate of the plant raw material according to the corresponding determined mass ratio, stirring is carried out at the optimal temperature and PH and the optimal rotating speed, and the temperature and rotating speed are monitored and controlled in real time through the PID controller, so that the amphiphilic substances form stable nanometer microspheres, and the effective components in the plant raw material are targetedly wrapped, i.e. the fat-soluble components are captured by the hydrophobic inner core, and the water-soluble components are combined on the surface of the microspheres through electrostatic action and hydrogen bond.

[0080] In order to accurately reflect the effect of different plant raw materials on the selection of amphiphilic substances and the ratio of nano-wrapping targeted extraction, the PID controller is used to control the temperature and rotating speed in real time, so as to avoid the instability of temperature and rotating speed, which may lead to insufficient assembly or microsphere aggregation, and further affect the extraction effect of plant effective components.

[0081] Specifically, based on the change characteristics of the monitored and collected temperature and rotating speed in the process of constructing the nano-wrapping system, the actual control process is optimized and adjusted, and the specific adjustment and analysis process is as follows:

[0082] Firstly, during the construction process of the nano-wrapping system, the temperature change affects the distribution of amphiphilic substances, which may lead to changes in the resistance of the mixed solution, causing fluctuations in the rotating speed, deviating from the preset parameter value, and affecting the structure and stability of the nano-wrapping particles. Therefore, for the construction of the nano-wrapping system, the temperature change and the fluctuation of the rotating speed have a lagging and cumulative influence on the assembly and aggregation of the amphiphilic substances.

[0083] In the actual control process, monitoring points for control optimization are set. The monitoring points can be uniformly set at equal intervals according to the actual construction. For example, if the stirring time is 30 min, the monitoring points are set at an interval of 1 min, and the number of monitoring points is 30.

[0084] Further, for each monitoring point set above, the two kinds of monitoring data collected up to the current monitoring point are respectively composed into time sequence according to time sequence, the difference between each element in the time sequence and the corresponding monitoring parameter preset value is calculated, and the ratio of the difference to the preset value is taken as the fluctuation deviation of the current monitoring point. The DTW distance is calculated as the characteristic difference value of the fluctuation deviation of the current monitoring point after the corresponding fluctuation deviations of the two kinds of monitoring data are sorted in time sequence.

[0085] The trend statistic of each kind of monitoring data collected at the current monitoring point is calculated by using the MK trend checking algorithm, and the mean value of the trend statistics corresponding to the two kinds of monitoring data is taken as the characteristic value of the fluctuation trend change of the current monitoring point.

[0086] The characteristic coefficient of the nano-encapsulation system construction control response is calculated based on the fluctuation deviation change difference and the trend change difference at each monitoring point in the monitoring process, and the calculation relationship is as follows: h x = a x × b x , wherein h x represents the characteristic coefficient of the nano-encapsulation system construction control response at the xth monitoring point in the control process; a x represents the characteristic difference value of the fluctuation deviation at the xth monitoring point in the control process; and b x represents the characteristic value of the fluctuation trend change at the xth monitoring point in the control process. The greater the corresponding calculated characteristic coefficient is, the more significant the stage control change characteristic of the fluctuation deviation is, and the more significant the influence of the change of the amphiphilic substance distribution in the nano-encapsulation system construction process is.

[0087] Further, based on the influence analysis of the stage change of the amphiphilic substance distribution of the monitoring data between different monitoring points, the deviation feedback characteristics of each monitoring data in the actual control process are comprehensively analyzed, the actual control deviation is adjusted based on the analysis result, and the influence of the change of the amphiphilic substance distribution characteristics on the actual nano-encapsulation system construction is responded in a timely manner.

[0088] Therefore, for each monitoring point, the mean value of the difference between all the monitoring data collected up to the current monitoring point and the preset value of the corresponding monitoring parameter is taken as the characteristic value of the cumulative control deviation at the current monitoring point in the control process, and the adjustment coefficient of the feedback correction deviation of each monitoring point is calculated based on the cumulative deviation influence in the actual control process and the characteristics of the data control response, and the calculation relationship is as follows:

[0089]

[0090] , wherein k x represents the adjustment coefficient of the feedback correction deviation at the xth monitoring point in the control process; h x represents the characteristic coefficient of the nano-encapsulation system construction control response at the xth monitoring point in the control process; n represents the number of monitoring points passed by the time when the current monitoring point is reached; μ x,i represents the absolute value of the difference between the characteristic values of the cumulative control deviation at the xth and ith monitoring points in the control process; and h x,i represents the absolute value of the difference between the characteristic coefficients of the nano-encapsulation system construction control response at the xth and ith monitoring points in the control process. The greater the absolute value of the calculated adjustment coefficient of the feedback correction deviation is, the greater the possibility that there is a large error in the deviation calculation caused by the temperature fluctuation and the speed fluctuation change under the current control.

[0091] Therefore, based on the influence of the stage-by-stage distribution change of the amphiphilic substance on the real-time control in the construction process of the nano-encapsulation system, a monitoring point is set to perform real-time deviation analysis to optimize and adjust the feedback error of the real-time control of the current monitoring point.

[0092] Specifically, at the moment corresponding to the monitoring point, the feedback deviation at the current moment is corrected and analyzed, the normalization processing result w of the adjustment coefficient of the feedback correction deviation of each monitoring point is obtained by using the normalization processing method, and the value of the current feedback deviation is adjusted based on the processing result, and the adjustment relationship is: Wherein σ is the value of the feedback deviation after adjustment at the xth monitoring point in the control process; σ0 is the value of the feedback deviation calculated at the xth monitoring point in the control process, which is determined by calculating the difference between each monitoring data collected at the xth monitoring point in the control process and the preset value of the corresponding monitoring parameter; τ is a preset feedback correction adjustment threshold value, which is determined by the average value of the adjustment coefficient obtained in the historical production monitoring process. That is, if the adjustment threshold value is exceeded, it means that the error of the feedback deviation value in the adjustment process at the moment corresponding to the monitoring point is larger than the actual deviation value, so the corresponding feedback deviation value is increased, and the influence of the change of the distribution characteristics of the amphiphilic substance on the actual nano-encapsulation system construction is responded in time, and more accurate control is realized.

[0093] Through the above process, the construction of the nano-encapsulation system of the functional ingredients in the filtrate extracted from the plant raw material is completed, and the mixed solution after nano-encapsulation is obtained.

[0094] S4 separation and purification and impurity removal: the mixed solution after the filtrate is encapsulated by the nano-encapsulation material obtained by step S3 is subjected to centrifugal and filtration treatment to obtain a clear filtrate containing nano-encapsulation complexes.

[0095] The mixed solution after the filtrate is encapsulated by the nano-encapsulation material obtained by step S3 is subjected to centrifugal treatment, wherein the centrifugal treatment is performed at a speed of 3000 r / min for 10 minutes to further remove the undissolved small drug residue particles in the mixed solution; after the centrifugal treatment, the solution is filtered through a 0.45 μm microporous filter to further intercept macromolecular impurities (such as residual starch particles and protein fragments), and a clear filtrate containing nano-encapsulation complexes is obtained.

[0096] S5 concentration and stability regulation: the clear filtrate is placed in a rotary evaporator for concentration to determine whether the ratio is adjusted.

[0097] The clear filtrate is placed in a rotary evaporator and concentrated at a temperature of 45-50°C and a vacuum of 0.08-0.09 MPa until the solid content of the clear filtrate reaches 20-30%; the system state is continuously observed during the concentration process: if turbidity or precipitation appears, it indicates that the mass ratio of the amphiphilic substances or the HLB value is not appropriate, and the mass ratio of the amphiphilic substances needs to be adjusted.

[0098] After the completion of the concentration, further processing is performed according to the target product form (such as a beverage, a pastry, or a wine additive): if used for a water-soluble product (for example, a beverage), it can be directly diluted with water; if used for a fat-soluble product (for example, a soft capsule), a suitable amount of vegetable oil can be added for dispersion, and the amphiphilicity of the nanoscale microspheres ensures their stable dispersion in different matrices.

[0099] Each of the embodiments in the present application is described in a progressive manner, and the same or similar parts between the embodiments can be referred to each other, and each embodiment mainly explains the difference from other embodiments.

[0100] It should be noted that unless otherwise specified and limited, terms such as "comprise", "include" or any other variants thereof are intended to cover non-exclusive inclusion, so that the circuit structure, article or device including a series of elements not only includes those elements, but also includes other elements not explicitly listed or inherent to such article or device. Without more limitation, the element limited by the phrase "including a" does not exclude the presence of another identical element in the article or device including the element. In addition, the term "and / or" used herein includes any and all combinations of one or more related listed items.

[0101] Other embodiments of the present application will be apparent to those skilled in the art upon consideration of the specification and practice of the application disclosed herein. The present application is intended to cover any variations, uses, or adaptations of the application following, in general, the principles of the application and including such departures from the present disclosure as come within known or customary practice in the art to which the application pertains.

[0102] It should be understood that the present application is not limited to the precise structures described above and illustrated in the drawings and that various modifications and changes can be made without departing from the scope thereof.

Claims

1. A nano-encapsulated targeted essence extraction process of medicinal plant active ingredients, characterized in that, The process comprises the following steps: S1 medicine pretreatment: screening, cleaning and crushing the raw materials of medicinal plants to obtain plant raw material particles; S2 solvent selection and extraction system construction: selecting a solvent to extract a filtrate containing active ingredients from the plant raw material particles; S3 nano-encapsulated material screening and nano-encapsulation system construction; specifically: (1) extracting the extract of several insoluble components in the filtrate to use the mass and HLB value of the extract as the satisfaction conditions for different assistant ratios for constructing nano-encapsulated material; (2) using the response surface method to obtain the optimal temperature, PH value and rotation speed parameters for constructing the nano-encapsulation system under different assistant ratios, and using the optimal parameters to control the temperature and rotation speed in real time during the nano-encapsulation system construction process based on an automatic control system; S4 separation, purification and impurity removal: centrifuging and filtering the mixed solution obtained by wrapping the filtrate with the nano-encapsulated material constructed in step S3 to obtain a clear filtrate containing nano-encapsulated complexes; S5 concentration and stability regulation: concentrating the clear filtrate in a rotary evaporator to determine whether to adjust the ratio; The specific process in (1) is as follows: Drying and weighing the filtrate of a predetermined volume to obtain the total mass; Adding the dried extract to petroleum ether for extraction and drying to obtain the weight of the petroleum ether extract; Drying the residue after extraction of the petroleum ether extract, adding a pre-determined concentration of ethanol for extraction to obtain the mass of the ethanol-soluble substance; Calculating the average HLB value of the mass and HLB value of the petroleum ether extract and the ethanol-soluble substance as the theoretical HLB value of all insoluble components; Calculating the amount of amphiphilic substance to be added using the total mass, the weight of the petroleum ether extract and the ethanol-soluble substance; The mass and average HLB value of the selected amphiphilic substance ratio for constructing the nano-encapsulated material meet the two conditions of the amount of the amphiphilic substance to be added and the theoretical HLB value; The calculation method of the amount of the amphiphilic substance to be added is as follows: wherein, represents the amount of the amphiphilic substance to be added; represents the total mass of the extract after drying the filtrate; , respectively represent the mass of the petroleum ether extract, the mass of the ethanol extract, i.e. the mass of all insoluble substances in the obtained extract; The real-time control of temperature and rotation speed during the nano-encapsulation system construction process based on the optimal parameters combined with an automatic control system includes: Setting monitoring points at equal time intervals according to the length of the nano-encapsulation system construction process; Grouping the two kinds of monitoring data collected up to the current monitoring point in time sequence to calculate the difference between each element in the time sequence and the corresponding monitoring parameter preset value, and taking the ratio of the difference to the preset value as the fluctuation deviation of the current monitoring point; calculating the DTW distance as the characteristic difference value of the fluctuation deviation of the current monitoring point after sorting all the fluctuation deviations between the two kinds of monitoring data in time sequence; Using the MK trend check algorithm to calculate the trend statistic of all fluctuation deviations of each kind of monitoring data collected at the current monitoring point, and taking the mean of the trend statistics corresponding to the two kinds of monitoring data as the characteristic value of the fluctuation trend change of the current monitoring point; Using the characteristic difference value and the fluctuation trend change characteristic value of the current monitoring point, calculate the characteristic coefficient of the nano-encapsulation system construction control response at the current monitoring point in the control process; The mean value of the difference between all monitoring data collected up to the current monitoring point and the preset value of the corresponding monitoring parameter is taken as the characteristic value of the cumulative control deviation at the current monitoring point in the control process; Based on the characteristic coefficient of the nano-encapsulated system construction control response at the current monitoring point in the control process and the characteristic value of the cumulative control deviation at the current monitoring point, the adjustment coefficient of the feedback correction deviation at the current monitoring point in the control process is calculated; The value of the feedback deviation calculated at the current monitoring point in the control process is adjusted by using the normalized value of the adjustment coefficient, so as to optimize and adjust the feedback error of the real-time control at the current monitoring point.

2. The medicinal plant active ingredient nano-encapsulated targeting refined extraction process as claimed in claim 1, wherein, The solvent is 70-75% ethanol; the mass-volume ratio of the mixed plant raw material particles and the solvent is 1:8-1:

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3. The medicinal plant active ingredient nano-encapsulated targeting refined extraction process as claimed in claim 1, wherein, The amphiphilic substances used for constructing the nano-encapsulated material include 2-3 kinds of auxiliary agents in monoglyceride fatty acid ester, Tween 80, phospholipid, polyethylene glycol and glycerol.

4. The medicinal plant active ingredient nano-encapsulated targeting refined extraction process as claimed in claim 1, wherein, The method for calculating the characteristic coefficients of the control response constructed by the nano-encapsulated system at the current monitoring point during the control process is as follows: ;in Indicates the control process in the first stage The characteristic coefficients of the control response were constructed using a nano-encapsulation system at each monitoring point. Indicates the control process in the first stage Characteristic differences in fluctuation deviations at each monitoring point; Indicates the control process in the first stage Characteristic values ​​of the fluctuation trend changes at each monitoring point.

5. The medicinal plant active ingredient nano-encapsulated targeted refined extraction process as claimed in claim 4, wherein, The calculation method of the adjustment coefficient of the feedback correction deviation at the current monitoring point in the control process is: wherein, represents the adjustment coefficient of the feedback correction deviation at the monitoring point in the control process; represents the number of monitoring points passed by the running to the time point at which the current monitoring point is located; represents the absolute value of the difference between the characteristic values of the cumulative control deviation at the monitoring point and the monitoring point in the control process; represents the absolute value of the difference between the characteristic coefficients of the nanoscale encapsulation system construction control response at the monitoring point and the monitoring point in the control process.

6. The medicinal plant active ingredient nano-encapsulated targeted refined extraction process as claimed in claim 5, wherein, The adjustment of the value of the feedback deviation calculated at the current monitoring point in the control process by using the normalized value of the adjustment coefficient includes: wherein is a value of the feedback deviation adjusted at the first monitoring point in the control process; is a value of the feedback deviation adjusted at the first monitoring point in the control process; is a value of the feedback deviation calculated at the first monitoring point in the control process; is a value of the feedback deviation calculated at the first monitoring point in the control process; is a value of the feedback deviation calculated at the first monitoring point in the control process; is a preset threshold value of the feedback correction adjustment.

7. The nano-encapsulation targeted extraction process for medicinal plant active ingredients as described in claim 1, characterized in that, The concentration conditions are that the temperature in the rotary evaporator is 45-50 DEG C, the vacuum degree is 0.08-0.09 MPa, and the solid content in the clear filtrate reaches 20%-30%.

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