Blueberry and grape seed xanthophyll preparation for relieving asthenopia and preparation method thereof

Abstract

The invention provides a blueberry and grape seed xanthophyll preparation for relieving asthenopia and a preparation method thereof. The preparation method comprises the following steps: converting xanthophyll into an oil phase; mixing a base catalyst, a phase transfer catalyst and pure water to obtain a water phase; flowing the oil phase through a tube pass of the hollow fiber membrane reactor with a first control parameter, and flowing the water phase through a shell pass of the hollow fiber membrane with a second control parameter; the oil phase and the water phase catalytically hydrolyze the xanthophyll at an oil phase-water phase interface, free xanthophyll is generated and retained in the oil phase, the dehydrated oil phase, the blueberry extract, the grape seed extract and carotene are mixed and homogenized to form uniform slurry, and free xanthophyll is obtained through hollow fiber membrane interface catalytic hydrolysis. The lutein isomerization loss caused by a strong alkali saponification process is avoided, the bioavailability and stability of active ingredients are improved, and the human body absorption rate is improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of health product production, and in particular to a blueberry grape seed lutein preparation for relieving visual fatigue and a preparation method thereof. BACKGROUND

[0002] Lutein is a natural fat-soluble carotenoid, is the core material of the human eye macula, can effectively filter blue light radiation, quench active oxygen free radicals, and has irreplaceable physiological effects on relieving visual fatigue and preventing macular lesions; blueberry anthocyanins and grape seed proanthocyanidins can enhance ocular microcirculation, inhibit the release of inflammatory factors, and synergistically improve visual function with lutein.

[0003] In the prior art, esterified lutein and plant extracts are directly mixed with a fixed formula, and the obtained preparation cannot simultaneously consider the bioavailability and stability of active ingredients, the human body absorption rate is insufficient, the traditional strong alkali saponification process leads to lutein isomerization loss, and physical mixing causes water and fat-soluble ingredients to separate, thereby reducing the bioavailability of the preparation. SUMMARY

[0004] The embodiment of the present application provides a blueberry grape seed lutein preparation for relieving visual fatigue and a preparation method thereof, and aims to solve the problems that the existing lutein preparation cannot simultaneously consider the bioavailability and stability of active ingredients, the human body absorption rate is insufficient, the traditional strong alkali saponification process leads to lutein isomerization loss, and physical mixing causes water and fat-soluble ingredients to separate, thereby reducing the bioavailability of the preparation. The free lutein is obtained by hollow fiber membrane interface catalytic hydrolysis, the bioavailability and stability of active ingredients are improved, and the human body absorption rate is improved.

[0005] In a first aspect, the embodiment of the present application provides a blueberry grape seed lutein preparation for relieving visual fatigue, which is prepared from the following raw materials in a ratio by weight: Blueberry extract: 90-150 parts; Grape seed extract: 50-100 parts; Carotene: 12-25 parts; Lutein: 4-8 parts; Vitamin E: 1-3 parts; Fish oil: 200-300 parts.

[0006] Further, the dosage form of the blueberry grape seed lutein preparation for relieving visual fatigue includes tablets or capsules.

[0007] The present application also provides a preparation method of a blueberry grape seed lutein preparation for relieving visual fatigue, which is used for preparing the blueberry grape seed lutein preparation for relieving visual fatigue as described in the present application, and the preparation method comprises: Preparing raw materials according to the ratio; converting the lutein into an oil phase; Specifically, the lutein can be mixed with a carrier oil to obtain the oil phase; Specifically, the carrier oil can be vitamin E and fish oil; mixing the base catalyst and the phase transfer catalyst with pure water to obtain an aqueous phase; flowing the oil phase through the tube side of the hollow fiber membrane reactor at a first control parameter, and flowing the aqueous phase through the shell side of the hollow fiber membrane at a second control parameter, the tube side being located within the shell side, and the hollow fiber membrane being between the tube side and the shell side; the oil phase and the aqueous phase have the hollow fiber membrane as an oil phase-aqueous phase interface, and the lutein is catalytically hydrolyzed at the oil phase-aqueous phase interface to generate free lutein, which is retained in the oil phase; collecting the oil phase product containing free lutein for dehydration, mixing the dehydrated oil phase with blueberry extract, grape seed extract, and carotene, and homogenizing to form a uniform slurry; processing the slurry according to the dosage form to obtain a blueberry grape seed lutein preparation for relieving visual fatigue.

[0008] Further, the method further comprises: during the process of catalytically hydrolyzing the lutein at the oil phase-aqueous phase interface, detecting the content distribution of the free lutein in the tube side in the oil phase; adjusting the first control parameter and the second control parameter according to the content distribution.

[0009] Further, the specific steps of detecting the content distribution of the free lutein in the tube side in the oil phase during the process of catalytically hydrolyzing the lutein at the oil phase-aqueous phase interface comprise: real-time acquisition of spectral data by optical fiber probes or optical imaging probes arranged at multiple online detection points to obtain the radial content of each online detection point, thereby obtaining the radial content distribution of the free lutein in the tube side, and the multiple online detection points being distributed axially; determining the axial content distribution of the free lutein in the tube side according to the radial content distribution of each online detection point.

[0010] Further, the step of adjusting the first control parameter and the second control parameter according to the content distribution specifically comprises: constructing a dynamic model of the concentration distribution of the free lutein; inputting the radial content distribution and the axial content distribution into the dynamic model to solve the first control parameter adjustment amount and the second control parameter adjustment amount; adjusting the first control parameter by the first control parameter adjustment amount, and adjusting the second control parameter by the second control parameter adjustment amount.

[0011] Further, the step of constructing the dynamic model of the free lutein concentration distribution specifically comprises: According to the columnar diffusion characteristics of the hollow fiber tube process, the nonlinear influence of the second control parameter on the reaction rate is associated, and the convection-diffusion-reaction equation of the free lutein in the tube process is established; The boundary conditions at the tube wall and the boundary conditions at the tube center are defined; According to the convection-diffusion-reaction equation, the boundary condition at the tube wall and the boundary condition at the tube center, a dynamic model of the free lutein concentration distribution is constructed.

[0012] Further, after the step of constructing the dynamic model of the free lutein concentration distribution, the method further comprises: Adjust the first control parameter and the second control parameter through orthogonal experiment, and collect the response data of the radial content distribution and the axial content distribution; Through the first control parameter, the second control parameter and the response data in the orthogonal experiment, the model parameters of the dynamic model are solved by parameter decoupling of the dynamic model; Based on the model parameters, a parameter mapping library is established; Based on the parameter mapping library, the dynamic model is calibrated.

[0013] Further, the step of mixing the dehydrated oil phase with the blueberry extract, grape seed extract and carotene to form a uniform slurry specifically comprises: Carotene is added to the dehydrated oil phase and stirred to form a premixed oil phase; The blueberry extract and grape seed extract are pre-mixed to obtain a solid extract compound; The premixed oil phase is transferred to a high-pressure homogenizer, and the solid extract compound is added multiple times under the protection of inert gas. After each addition of the solid extract compound, the slurry is homogenized by pressurization to form a uniform slurry.

[0014] Further, the step of homogenizing by pressurization to form a uniform slurry specifically comprises: The particle size distribution of the slurry is detected by an online laser particle size analyzer after each homogenization; If the particle size distribution of the slurry does not meet the homogenization conditions corresponding to the current homogenization, the pressure parameter of the next homogenization is adjusted, and each homogenization corresponds to different homogenization conditions; After the last homogenization, a uniform slurry is formed.

[0015] The blueberry grape seed lutein preparation for relieving visual fatigue in the embodiment of the present application is prepared from the following raw materials in the proportion of parts by weight: blueberry extract: 90-150 parts; grape seed extract: 50-100 parts; carotene: 12-25 parts; lutein: 4-8 parts; vitamin E: 1-3 parts; and fish oil: 200-300 parts. The present application converts lutein into an oil phase; mixes an alkali catalyst, a phase transfer catalyst and pure water to obtain an aqueous phase; flows the oil phase through the tube side of a hollow fiber membrane reactor at a first control parameter, and flows the aqueous phase through the shell side of the hollow fiber membrane at a second control parameter; catalytically hydrolyzes lutein at the oil phase-aqueous phase interface to generate free lutein which is retained in the oil phase, mixes the dehydrated oil phase with the blueberry extract, grape seed extract and carotene, homogenizes to form a uniform slurry, and obtains free lutein through the interface catalytic hydrolysis of the hollow fiber membrane, thereby avoiding the isomerization loss of lutein caused by the strong alkali saponification process, improving the bioavailability and stability of the active ingredients, and improving the human absorption rate. BRIEF DESCRIPTION OF DRAWINGS

[0016] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or the prior art description. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without any creative effort on the basis of these drawings.

[0017] Figure 1 is a flow chart of a preparation method of a blueberry grape seed lutein preparation for relieving visual fatigue provided by the embodiment of the present application; Figure 2 is a flow chart of another preparation method of a blueberry grape seed lutein preparation for relieving visual fatigue provided by the embodiment of the present application; Figure 3 is a specific flow chart of step S8 in the embodiment of the present application; Figure 4 is another specific flow chart of step S9 in the embodiment of the present application; Figure 5 is a specific flow chart of step S91 in the embodiment of the present application; Figure 6 is another specific flow chart of step S91 in the embodiment of the present application; Figure 7 is a specific flow chart of step S6 in the embodiment of the present application; Figure 8 is a specific flow chart of step S63 in the embodiment of the present application. DETAILED DESCRIPTION

[0018] With reference to the accompanying drawings, the technical solutions in the embodiments of the present application will be clearly and completely described in the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments of the present application, all other embodiments obtained by those skilled in the art without creative work fall within the scope of the present application.

[0019] The blueberry grape seed lutein preparation for relieving asthenopia is prepared from the following raw materials in the proportion of parts by weight: Blueberry extract: 90-150 parts; Grape seed extract: 50-100 parts; Carotene: 12-25 parts; Lutein: 4-8 parts; Vitamin E: 1-3 parts; Fish oil: 200-300 parts.

[0020] In the embodiments of the present application, the blueberry extract is prepared from blueberries as raw materials, extracted by water or ethanol, concentrated, and dried to obtain a content of anthocyanins ≥25%. The core active ingredient is anthocyanins, which has the effects of scavenging free radicals and improving microcirculation.

[0021] The grape seed extract is derived from grape seeds, and the proanthocyanidin content in the standardized extract is ≥95%. It protects the retinal vascular endothelium by inhibiting collagenase.

[0022] Lutein is a natural lutein crystal with a purity ≥80%. It is selectively enriched in the macular area of the retina, filters blue light, and inhibits lipid peroxidation.

[0023] Carotene can include β-carotene or mixed carotenoids (such as α-carotene, lutein ester), and the total carotene content is ≥90%. As a precursor of vitamin A, it participates in the regeneration of rhodopsin.

[0024] Vitamin E can be natural tocopherol or its ester, with a content ≥96%. It is a fat-soluble antioxidant that protects cell membranes from oxidative damage.

[0025] Fish oil can be refined fish oil from deep-sea fish, with an EPA+DHA content ≥30%. It provides ω-3 polyunsaturated fatty acids and inhibits the expression of inflammatory factors in the retina.

[0026] The blueberry extract, grape seed extract, lutein, and carotene can be respectively passed through an 80-mesh sieve, and the vitamin E is dispersed into a liquid state by a colloid mill for standby; the fish oil is filtered by a 0.45 μm filter to remove impurities, and is kept at 40°C for standby.

[0027] Each raw material is weighed by parts by weight: 90-150 parts of blueberry extract, 50-100 parts of grape seed extract, 12-25 parts of carotene, and 4-8 parts of lutein; 200-300 parts of fish oil is added, and stirred at 500 rpm for 10 minutes in a nitrogen environment; 1-3 parts of vitamin E is added, and the temperature is raised to 50±2℃, and homogenized at high speed (10,000 rpm) for 15 minutes to form a uniform oil phase suspension.

[0028] The suspension is filled into soft capsules, each containing 500 mg of active substance; the capsules are dried (humidity ≤5%), aluminum-plastic packaged in the dark, and stored in a cool and dry place (≤25℃). The suspension can also be increased in viscosity and pressed into tablets.

[0029] In this embodiment, the anthocyanins in the blueberry extract can activate the regeneration of rhodopsin, enhance the ability of dark adaptation, and inhibit the VEGF pathway to reduce vascular leakage. Further, it can improve the clarity of night vision and relieve eye swelling and pain.

[0030] The proanthocyanidins in the grape seed extract can scavenge ROS and inhibit MMP-9 enzyme to protect the retinal basement membrane. Further, it can reduce the oxidative damage of the retina caused by screen blue light.

[0031] Lutein + carotene can form a "blue light filter" in the macular area, quench singlet oxygen, and promote the synthesis of photoreceptor cells. Further, it can reduce glare sensitivity and delay the time of visual blurring.

[0032] Vitamin E + EPA / DHA in fish oil can inhibit the TNF-α inflammatory pathway; vitamin E prevents lipid peroxidation chain reaction. It can synergistically protect the stability of the tear film and relieve dry eye symptoms.

[0033] The blueberry grape seed lutein preparation for relieving visual fatigue in the present application has the effects of making the eyes comfortable, moist, bright, and clear, reducing blood vessels, and smoothing eye lines, etc. through the above effective ingredients.

[0034] Further, the dosage form of the blueberry grape seed lutein preparation for relieving visual fatigue includes tablets or capsules.

[0035] In this embodiment, the tablet can be a solid dosage form prepared by compressing the active ingredients and pharmaceutical excipients through a tabletting process. The coating layer accounts for 3-5% of the tablet weight and includes a separation layer, a light shielding layer, and an enteric layer. The separation layer can be made of hydroxypropyl methylcellulose (HPMC) solution to prevent fish oil from migrating to the surface; the light shielding layer can be made of titanium dioxide (TiO2) suspension to block ultraviolet rays; and the enteric layer can be made of acrylic resin (Eudragit L30D-55) to ensure that the active ingredients are in the intestine.

[0036] The tablet preparation process is as follows: Mix blueberry extract, grape seed extract, carotene and microcrystalline cellulose (filler, 50 parts); Spray in a dehydrated oil phase of fish oil, vitamin E, and lutein (200 parts fish oil + 3 parts vitamin E + 8 parts lutein), and granulate in a fluidized bed (inlet air temperature 40℃); add croscarmellose sodium (disintegrant, 8 parts), and granulate to obtain granules.

[0037] The granules are mixed with magnesium stearate (lubricant, 1 part) and compressed into tablets (1000 mg / tablet).

[0038] Spray the following layers in sequence: 5% hydroxypropyl methylcellulose solution as an isolation layer; Opadry suspension containing 15% TiO2 as a light-shielding layer; and Eudragit L30D-55 as an enteric coating layer.

[0039] After homogenizing the above formulation, the mixture is refined to a particle size ≤50μm using a colloid mill. The active ingredients are adsorbed onto silica and then filled into DRcaps® capsules. The capsules are then formed using a rotary molding process at 25°C and 40% humidity. Aluminum-aluminum blister packaging is used.

[0040] like Figure 1 As shown, Figure 1 This is a flowchart illustrating a method for preparing a blueberry and grape seed lutein preparation for relieving eye strain, as provided in an embodiment of the present invention. The method comprises the following steps: S1. Prepare the raw materials according to the formula.

[0041] S2 converts lutein into an oil phase, which can be obtained by mixing lutein with a carrier oil. The specific carrier oil can be vitamin E and fish oil.

[0042] S3, the alkaline catalyst, phase transfer catalyst and pure water are mixed to obtain an aqueous phase.

[0043] The alkaline catalyst can be food-grade potassium hydroxide or sodium hydroxide at a concentration of 5-8 wt%, requiring ICP testing to detect metal ion residues of ≤10 ppm. The phase transfer catalyst can be benzyltriethylammonium chloride, tetrabutylammonium bromide, or tea saponin, etc.

[0044] S4, the oil phase flows through the tube side of the hollow fiber membrane reactor with a first control parameter, and the aqueous phase flows through the shell side of the hollow fiber membrane with a second control parameter.

[0045] The tube passage is located in the shell passage, and the hollow fiber membrane is between the tube passage and the shell passage.

[0046] S5, the oil phase and the water phase are separated by the hollow fiber membrane, and the catalytic hydrolysis of the xanthophyll is carried out at the oil phase-water phase interface, so that the free xanthophyll is generated and retained in the oil phase.

[0047] The free xanthophyll refers to the non-esterified xanthophyll generated by hydrolysis of xanthophyll ester, and the human body absorption rate of xanthophyll can be further improved.

[0048] S6, the oil phase product containing the free xanthophyll is collected for dehydration, and the dehydrated oil phase is mixed with blueberry extract, grape seed extract and carotene to form a uniform slurry.

[0049] S7, the slurry is processed according to the dosage form to obtain a blueberry grape seed xanthophyll preparation for relieving visual fatigue.

[0050] In the embodiment of the present application, the raw materials are prepared according to the following ratio by weight: blueberry extract: 90-150 parts; grape seed extract: 50-100 parts; carotene: 12-25 parts; xanthophyll: 4-8 parts; vitamin E: 1-3 parts; and fish oil: 200-300 parts. Different ratios can be selected according to different product models.

[0051] In an oxygen-controlled environment, the xanthophyll ester, vitamin E and fish oil are mixed in proportion, nitrogen gas is used to replace oxygen, the dissolved oxygen is ≤0.5 ppm, heating is carried out to 50±2℃ to completely dissolve, and a 5μm titanium filter is used to filter, so as to prepare the oil phase.

[0052] KOH (6wt%) and TEBAC (1wt%) are dissolved in pure water, and the temperature is controlled at 45±1℃ to avoid KOH crystallization, so as to prepare the water phase.

[0053] In the hollow fiber membrane reactor, the oil phase flows into the tube passage, and the water phase flows into the shell passage. The first control parameters include the tube passage flow rate, the tube passage temperature and the tube passage pressure, and the second control parameters include the shell passage flow rate, the shell passage temperature, the shell passage pressure and the catalyst concentration. The tube passage flow rate is set to 0.8-1.2 mL / min·fiber, and the shell passage flow rate is set to 3-5 mL / min·fiber, so as to maintain laminar flow and avoid emulsification. The tube passage temperature is set to 50±1℃, and the shell passage temperature is set to 45±1℃, so as to balance the reaction rate and the membrane stability. The shell passage pressure is greater than the tube passage pressure, and the pressure difference is kept within 0.05-0.1 MPa to prevent the oil phase from penetrating into the water phase.

[0054] Lutein in the oil phase and OH in the water phase - and TEBAC diffuses through the membrane pores to the oil-water interface, catalyzes the hydrolysis of lutein at the oil-water interface, and obtains free lutein. Due to the lipophilicity of free lutein, free lutein returns and remains in the oil phase. As the oil phase is collected from the tube side outlet, the potassium salt of fatty acid remains in the water phase, and the water phase enters the water circulation system from the shell side outlet.

[0055] The collected oil phase product can be dehydrated by molecular sieve adsorption, so that the water content is ≤0.1%. The dehydrated oil phase is mixed with blueberry extract, grape seed extract, and carotene in a high-speed shear emulsifier (15,000 rpm, 10 min) to form a uniform slurry. The slurry is processed according to the above dosage form to obtain a blueberry grape seed lutein preparation for relieving visual fatigue.

[0056] Compared with the traditional process, the hydrolysis efficiency is improved compared with the traditional saponification method of two-phase emulsification. The reaction is emulsified at the oil-water interface, which improves the conversion efficiency of free lutein. In terms of separation difficulty, compared with the traditional saponification method which needs to be centrifuged to break the emulsion, the recovery rate is low. In this embodiment, the oil phase and the water phase are physically separated by a hollow fiber membrane, which is easy to separate.

[0057] In the embodiment of the present application, the blueberry grape seed lutein preparation for relieving visual fatigue is prepared from the following raw materials in the following weight ratio: blueberry extract: 90-150 parts; grape seed extract: 50-100 parts; carotene: 12-25 parts; lutein: 4-8 parts; vitamin E: 1-3 parts; fish oil: 200-300 parts. The present application converts lutein into an oil phase; mixes an alkali catalyst, a phase transfer catalyst, and pure water to obtain a water phase; flows the oil phase through the tube side of the hollow fiber membrane reactor at a first control parameter, and flows the water phase through the shell side of the hollow fiber membrane at a second control parameter; catalyzes the hydrolysis of lutein at the oil-water interface to generate free lutein, which is retained in the oil phase; mixes the dehydrated oil phase with blueberry extract, grape seed extract, and carotene to form a uniform slurry; and catalyzes the hydrolysis of lutein at the interface of the hollow fiber membrane to obtain free lutein, thereby avoiding the isomerization loss of lutein caused by the strong alkali saponification process, improving the stability of active ingredients, and improving the bioavailability of active ingredients by using the human body to absorb free lutein.

[0058] Further, as shown in Figure 2 the method further comprises: S8, detecting the content distribution of free lutein in the tube side during the process of catalyzing the hydrolysis of lutein at the oil-water interface.

[0059] S9, adjusting the first control parameter and the second control parameter according to the content distribution.

[0060] In the embodiment of the present application, the content distribution of free lutein in the oil phase in the tube pass can be detected by a content distribution detection system, which can be composed of an array of fiber near-infrared probes (NIR) distributed equidistantly along the axial direction of the membrane tube pass (with a spacing of 10 cm). The detection wavelength of the fiber near-infrared probe is set to 1200-2400 nm, and the characteristic peak of free lutein is 1660 nm. The resolution is set to ±0.5 wt%, and the sampling frequency is 1 Hz.

[0061] The first control parameter refers to the flow rate, temperature, and pressure of the tube pass (oil phase), and the control accuracy can be set to flow rate ±0.05 mL / min·fiber, temperature ±0.5℃, and pressure ±0.01 MPa. The second control parameter refers to the KOH concentration, TEBAC concentration, and flow rate of the shell pass (water phase), and the control method is to dynamically supplement the concentrated liquid by a metering pump. The supplemented concentrated liquid can be 20% KOH or 5% TEBAC.

[0062] Specifically, NIR probes are arranged at multiple axial points of the tube pass of the membrane reactor, such as the inlet, outlet, L / 4, L / 2, and 3L / 4, to obtain the free lutein concentration values at each point in real time. .

[0063] The free lutein concentration values at the points arranged in the order from the inlet to the outlet are taken as an example, and the concentration gradient deviation value can be calculated by the following formula: ; Wherein, N 1 represents the first point among the points, N 1 and N 2 represent the last two points among the points, N 1 and N 2, and the boundary between N 1 and N 2 is the point whose concentration difference with the first point is less than the pre-set concentration difference threshold value, N 1 is the point before the first point, 2 is the point after the first point, i is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point; N is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point; i is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point; N is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point; i is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point; is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point; i is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point; is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point; i is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point; is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point; is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point; j is the time for the oil phase to flow from the first point to the second point, which can be calculated according to the flow rate of the oil phase and the distance between the first point and the second point;​​ The time of each point can be calculated according to the oil phase flow rate and the distance between the first point and the second point. j The time of each point can be calculated according to the oil phase flow rate and the distance between the first point and the second point. The time of each point can be calculated according to the oil phase flow rate and the distance between the first point and the second point.

[0064] Specifically, if the concentration of the point is lower than the pre-set point concentration range, the oil phase flow rate can be reduced or the water phase KOH concentration can be increased, the reaction time can be prolonged or the hydrolysis strength can be enhanced; if the concentration gradient deviation is greater than the concentration gradient deviation threshold value, it indicates that the concentration gradient deviation is large, generally, the reaction at the first point is the head, and the reaction at the second point is the tail, the concentration gradient deviation is large, which indicates that the reaction degree of the head and the tail is large, the mass transfer uniformity is poor, at this time, the oil phase temperature can be increased, the TEBAC concentration can be increased, and the mass transfer uniformity can be improved. The concentration gradient deviation is greater than the concentration gradient deviation threshold value. The concentration gradient deviation is greater than the concentration gradient deviation threshold value. N The concentration gradient deviation is greater than the concentration gradient deviation threshold value. N The concentration gradient deviation is greater than the concentration gradient deviation threshold value. The concentration gradient deviation is greater than the concentration gradient deviation threshold value.

[0065] Through the adaptive dynamic feedback control, the consistency of the free lutein content in the phase temperature can be improved.

[0066] Further, as shown in the oil phase-water phase interface, the specific steps for detecting the content distribution of free lutein in the pipe in the process of catalyzing and hydrolyzing lutein include: Figure 3 S81, the optical fiber probe or the optical imaging probe arranged at the multiple online detection points is used to collect spectrum data in real time, the radial content of each online detection point is collected, and the radial content distribution of free lutein in the pipe is obtained. The multiple online detection points are axially distributed.

[0067] S82, according to the radial content distribution of each online detection point, the axial content distribution of free lutein in the pipe is determined.

[0068] In the embodiment of the present application, the optical fiber probe is a NIR probe, and the optical imaging probe can be a confocal Raman spectrum probe, which uses 785nm laser for detection, the spatial resolution is radial ±10μm and axial ±50μm, the scanning frequency is 5 frames / second, and the full cross-section scanning mode is used.

[0069] The radial content distribution refers to the concentration gradient of free lutein from the center of the pipe to the pipe wall in the cross-section of a single detection point. The axial content distribution is constructed by integrating the radial distribution of multiple detection points, and is specifically shown in the following formula:

[0070] The axial content distribution is the axial content distribution, The radial coordinate is the radial coordinate, The axial content distribution is the axial content distribution, ​​For the tube radius, represents the free lutein concentration in the tube with coordinates

[0071] In the probe arrangement, an axial spacing is arranged between the two probes, and the axial spacing is adapted to the fluid characteristics of the flow pattern development zone of the hollow fiber membrane reactor. The radial scanning points are equiangularly distributed.

[0072] The radial scanning calibration can be performed using the Raman spectrum of a standard glycerol-lutein solution, and the Raman peak intensity corresponding to free lutein is 1660. Mapping calibration is performed by the following formula: ; wherein, is the Raman peak intensity corresponding to free lutein, C is the concentration corresponding to free lutein. According to the concentration data in the calibration process, the concentration deviation and the standard deviation are calculated, and if the concentration deviation of a certain radial point is > 3σ, σ is the standard deviation of adjacent online detection points, the self-cleaning program is started, and the abnormal points are filtered.

[0073] In this embodiment, radial + axial double-dimensional monitoring is adopted, which can automatically and quickly identify tube wall deposition, prewarn membrane pollution, and feedback to the first control parameter and the second control parameter for adjustment, thereby improving the hydrolysis precision and ensuring the hydrolysis uniformity.

[0074] Further, as shown in Figure 4 , the step of adjusting the first control parameter and the second control parameter according to the content distribution specifically includes: S91, a dynamic model of the free lutein concentration distribution is constructed.

[0075] S92, the radial content distribution and the axial content distribution are input into the dynamic model, and the first control parameter adjustment amount and the second control parameter adjustment amount are solved.

[0076] S93, the first control parameter is adjusted by the first control parameter adjustment amount, and the second control parameter is adjusted by the second control parameter adjustment amount.

[0077] In the embodiments of the present application, the above dynamic model can be a digital twin model or a differential control model. The digital twin model is modeled according to the real-time acquisition data of the hollow fiber membrane reactor, so as to analyze the real-time dynamic concentration of the hollow fiber membrane reactor in real time, and to calculate the optimal first control parameter and second control parameter adjustment scheme according to the simulation control.

[0078] The differential control model has interpretability, so that the adjustment process of the control parameter is more intuitive and has a basis.

[0079] After the dynamic model is constructed, if the dynamic model is a digital twin model, the radial content distribution and the axial content distribution are input into the dynamic model, and the first control parameter adjustment amount and the second control parameter adjustment amount are solved through simulation control. The first control parameter is adjusted through the first control parameter adjustment amount. If the first control parameter adjustment amount is positive, the first control parameter adjustment amount is added to the first control parameter. If the first control parameter adjustment amount is negative, the first control parameter adjustment amount is subtracted from the first control parameter. The second control parameter is adjusted through the second control parameter adjustment amount. If the second control parameter adjustment amount is positive, the second control parameter adjustment amount is added to the second control parameter. If the second control parameter adjustment amount is negative, the second control parameter adjustment amount is subtracted from the second control parameter.

[0080] Through the dynamic model, the real-time adjustment amount of the first control parameter and the second control parameter can be calculated in real time, so as to adjust the hydrolysis process in real time, further improve the hydrolysis precision, and ensure the hydrolysis uniformity.

[0081] Further, as shown in Figure 5 The step of constructing the dynamic model of the free state lutein concentration distribution specifically includes: S911, according to the columnar diffusion characteristics of the hollow fiber pipe, the nonlinear influence of the second control parameter on the reaction rate is associated, and the convection-diffusion-reaction equation of the free state lutein in the pipe is established.

[0082] S912, the boundary conditions at the pipe wall and the pipe center are defined.

[0083] S913, according to the convection-diffusion-reaction equation, the boundary condition at the pipe wall and the boundary condition at the pipe center, a dynamic model of the free state lutein concentration distribution is constructed.

[0084] In the embodiment of the application, the above dynamic model is a differential control model, and the convection-diffusion-reaction equation of the free state lutein in the pipe is as follows: ; Among them, C represents the free state lutein concentration, v represents the oil phase flow rate, z represents the axial coordinate of the pipe, r represents the radial coordinate of the pipe, D represents the effective diffusion coefficient of lutein in the oil phase, represents the interfacial hydrolysis reaction rate constant, represents the initial concentration of lutein, represents the hydrolysis reaction activation energy, R represents the radius of the pipe, T represents the temperature of the water phase. is the radial term, which is used to describe the cylindrical diffusion of the hollow fiber membrane tube, is the exponential term, which is related to the nonlinear effect of the water phase temperature on the reaction rate, and explains the abnormality of the axial distribution. The effective diffusion coefficient D is calculated from the oil phase viscosity: , represents the oil phase viscosity, which can be obtained by reading the data of the viscosity sensor arranged in the oil phase in real time. The interfacial hydrolysis reaction rate constant can be fed back by the water phase pH sensor, specifically by measuring the pH value of the water phase, and mapping it through the linear model of pH and . The second control parameter (catalyst concentration) can be obtained by looking up the table through the interfacial hydrolysis reaction rate constant and the water phase temperature T . Through experimental data, statistical analysis of the T under different catalyst concentrations can be obtained , so that after obtaining and T , the corresponding catalyst concentration is found.

[0085] The boundary condition at the tube wall is as follows: ; wherein, represents the tube wall, κ represents the membrane mass transfer coefficient, which is positively correlated with the phase transfer catalyst concentration, represents the free lutein concentration at the tube wall. The membrane mass transfer coefficient κ is obtained by looking up the phase transfer catalyst concentration, and the concentration-mass transfer coefficient mapping table is pre-stored through experiments.

[0086] The boundary condition at the tube center is as follows: ; wherein, r = 0 represents the tube center.

[0087] The dynamic model of the free lutein concentration distribution can be as follows: ; ; ; The dynamic model of the free lutein concentration distribution described above improves the accuracy of the parameter control process by introducing the tube column coordinate exclusive equation to describe the cylindrical diffusion of the hollow fiber membrane tube, further improves the hydrolysis accuracy, and guarantees the uniformity of hydrolysis.

[0088] Further, as Figure 6As shown, after the step of constructing a dynamic model of the concentration distribution of free lutein, the method further comprises: S914, adjusting the first control parameter and the second control parameter through orthogonal experiment, collecting response data of the radial content distribution and the axial content distribution.

[0089] S915, parameter decoupling of the dynamic model through the first control parameter, the second control parameter and the response data in the orthogonal experiment, and solving model parameters of the dynamic model.

[0090] S916, establishing a parameter mapping library based on the model parameters.

[0091] S917, calibrating the dynamic model based on the parameter mapping library.

[0092] In the embodiment of the application, in the orthogonal experiment, a certain second control parameter is fixed, and the first control parameter (oil phase flow rate) is adjusted multiple times to obtain multiple groups of response data of the hollow fiber membrane reactor, each group of response data corresponding to one adjustment, and the above-mentioned response data including response data of the radial content distribution and the axial content distribution. Similarly, a certain first control parameter is fixed, and the second control parameter (catalyst concentration and water phase temperature) is adjusted multiple times to obtain multiple groups of response data of the hollow fiber membrane reactor, each group of response data corresponding to one adjustment, and the above-mentioned response data including response data of the radial content distribution and the axial content distribution.

[0093] The diffusion equation is fitted through the radial distribution data , and the effective diffusion coefficient D is solved as shown in the following formula: ; The membrane mass transfer coefficient κ is solved from the pipe wall boundary condition, and is specifically shown in the following formula: ; wherein, delta represents the membrane thickness (pipe thickness) of the hollow fiber membrane, which is a preset value.

[0094] The reaction term is substituted by the axial distribution data , and the interface hydrolysis reaction rate constant , the hydrolysis reaction activation energy are solved by least square fitting.

[0095] The quantization relationship mapping table of the effective diffusion coefficient , the membrane mass transfer coefficient , is generated respectively, and each quantization relationship mapping table is stored in the parameter mapping library. The dynamic model is calibrated based on the parameter mapping library.

[0096] The calibration of the radial / axial parameter coupling of the hollow fiber reactor makes the dynamic model more accurately adapt to the hollow fiber reactor, and further improves the accuracy of parameter control.

[0097] Further, as shown in Figure 7 The step of mixing the dehydrated oil phase with the blueberry extract, grape seed extract, and carotene, and homogenizing to form a uniform slurry specifically includes: S61, adding carotene to the dehydrated oil phase and stirring to form a premixed oil phase.

[0098] S62, pre-mixing the blueberry extract and grape seed extract to obtain a solid extract compound.

[0099] S63, transferring the premixed oil phase to a high-pressure homogenizer, adding the solid extract compound multiple times under inert gas protection, and after each addition of the solid extract compound, homogenizing by pressurization to form a uniform slurry.

[0100] In the embodiment of the present application, the dehydrated oil phase is heated to 35-40°C, carotene is added and stirred at 2000-3000 rpm for 10-15 minutes to form a premixed oil phase; the blueberry extract and grape seed extract are pre-mixed at a mass ratio of 1:1-1.5 to obtain a solid extract compound.

[0101] The premixed oil phase is transferred to a high-pressure homogenizer, and the solid extract compound is added multiple times under inert gas protection (nitrogen or argon); after each addition, it is homogenized at a pressure of 50-100 MPa for 30-60 seconds, and the temperature is controlled at ≤45°C; after homogenization, the slurry viscosity is detected, if the viscosity >5000 cP, then supplement the premixed oil phase. If the viscosity <3000 cP, then supplement the solid extract compound. Through inert gas protection, the oxidation path of blueberry anthocyanins and grape seed polyphenols can be effectively blocked.

[0102] In this embodiment, the oil phase and carotene are mixed first, which can make the carotene fully dissolve in the oil phase, prevent subsequent agglomeration, and avoid the appearance of particles in the slurry. Pre-mixing blueberries and grape seeds can balance the pH of anthocyanins and proanthocyanidins, and prevent local pH mutations from causing ingredient degradation.

[0103] In this embodiment, multiple homogenization combined with gradient mixing can avoid sedimentation caused by density differences. No emulsifiers, preservatives or synthetic aids are added during the preparation of the slurry, and only physical processes are used to achieve stability.

[0104] Further, as shown in Figure 8 The step of homogenizing by pressurization to form a uniform slurry specifically includes: S631, detecting the particle size distribution of the slurry by an online laser particle size analyzer after each homogenization.

[0105] S632, if the slurry particle size distribution does not meet the homogenization condition corresponding to the current homogenization treatment, adjusting the pressure parameter of the next homogenization treatment, and each homogenization treatment corresponds to different homogenization conditions.

[0106] S633, after the last homogenization treatment, forming a uniform slurry.

[0107] In the embodiment of the present application, the online laser particle size analyzer adopts dynamic light scattering (DLS) principle to carry out particle size sampling, the measurement range is set to 0.1-1000 μm, the accuracy is set to ±1%, and the sampling is 1 time / 10 seconds. The homogenization condition is related to the order of homogenization treatment, and the adjustment of the pressure parameter of homogenization treatment is also related to the order of homogenization treatment, which is shown in the following table: ; By controlling the pressure parameter of each order homogenization treatment through gradient, the effect of homogenization treatment can be better, and the homogeneity of the slurry can be improved.

[0108] The above only discloses the preferred embodiments of the present application, and of course cannot limit the scope of the rights of the present application, so the equivalent changes made according to the claims of the present application still belong to the scope covered by the present application.

Claims

1. A blueberry and grape seed lutein preparation for relieving eye strain, characterized in that, It is prepared from the following raw materials in the following proportions by weight: Blueberry extract: 90-150 parts; Grape seed extract: 50-100 parts; Carotene: 12-25 servings; Lutein: 4-8 parts; Vitamin E: 1-3 servings; Fish oil: 200-300 servings.

2. The blueberry and grape seed lutein preparation for relieving eye strain as described in claim 1, characterized in that, The dosage forms of the blueberry and grape seed lutein preparation for relieving eye strain include tablets or capsules.

3. A method for preparing a blueberry and grape seed lutein preparation to relieve eye strain, characterized in that, The method for preparing the blueberry grape seed lutein preparation for relieving eye strain as described in claim 1 or 2 includes: Prepare the raw materials according to the specified ratio; Convert lutein into the oil phase; The oil phase can be obtained by mixing lutein with a carrier oil; The carrier oil can be vitamin E and fish oil; An aqueous phase is obtained by mixing an alkaline catalyst, a phase transfer catalyst, and pure water. The oil phase flows through the tube side of the hollow fiber membrane reactor with a first control parameter, and the aqueous phase flows through the shell side of the hollow fiber membrane with a second control parameter. The tube side is located inside the shell side, and the hollow fiber membrane is between the tube side and the shell side. The oil phase and the water phase are separated by a hollow fiber membrane as the oil-water phase interface. Lutein is catalytically hydrolyzed at the oil-water phase interface to generate free lutein which is retained in the oil phase. The oil phase product containing free lutein was collected and dehydrated. The dehydrated oil phase was mixed with blueberry extract, grape seed extract and carotene, and homogenized to form a homogeneous slurry. The slurry was processed into dosage forms to obtain a blueberry and grape seed lutein preparation that relieves eye strain.

4. The method for preparing the blueberry and grape seed lutein preparation for relieving eye fatigue as described in claim 3, characterized in that, The method further includes: During the catalytic hydrolysis of lutein at the oil-water interface, the content distribution of free lutein in the oil phase in the tube side was detected. Based on the content distribution, the first control parameter and the second control parameter are adjusted.

5. The method for preparing a blueberry and grape seed lutein preparation for relieving eye strain as described in claim 4, characterized in that, In the process of catalytic hydrolysis of lutein at the oil-water interface, the specific steps for detecting the content distribution of free lutein in the oil phase in the tube pass include: Spectral data is collected in real time by fiber optic probes or optical imaging probes set up at multiple online detection points. The radial content of each online detection point is collected, and the radial content distribution of free lutein in the tube is obtained, as well as the axial distribution of multiple online detection points. Based on the radial content distribution at each online detection point, the axial content distribution of free lutein in the tube was determined.

6. The method for preparing the blueberry and grape seed lutein preparation for relieving eye fatigue as described in claim 5, characterized in that, The steps for adjusting the first control parameter and the second control parameter based on the content distribution specifically include: Construct a dynamic model of the concentration distribution of free lutein; The radial content distribution and the axial content distribution are input into the dynamic model to solve for the adjustment amount of the first control parameter and the adjustment amount of the second control parameter. The first control parameter is adjusted by the first control parameter adjustment amount, and the second control parameter is adjusted by the second control parameter adjustment amount.

7. The method for preparing the blueberry and grape seed lutein preparation for relieving eye fatigue as described in claim 6, characterized in that, The specific steps for constructing a dynamic model of the concentration distribution of free lutein include: Based on the columnar diffusion characteristics of the hollow fiber tube, and by associating the nonlinear effect of the second control parameter on the reaction rate, a convection-diffusion-reaction equation for free lutein in the tube is established. Define the boundary conditions at the pipe wall and the pipe center; Based on the convection-diffusion-reaction equation, the boundary conditions at the tube wall, and the boundary conditions at the tube center, a dynamic model of the free lutein concentration distribution is constructed.

8. The method for preparing the blueberry and grape seed lutein preparation for relieving eye fatigue as described in claim 7, characterized in that, After the step of constructing a dynamic model of the concentration distribution of free lutein, the method further includes: By adjusting the first and second control parameters through orthogonal experiments, response data of radial and axial content distributions were collected. By using the first control parameter, the second control parameter, and the response data in the orthogonal experiment, the dynamic model is decoupled from its parameters, and the model parameters of the dynamic model are solved. Based on the model parameters, a parameter mapping library is established; The dynamic model is calibrated based on the parameter mapping library.

9. The method for preparing a blueberry and grape seed lutein preparation for relieving eye strain as described in any one of claims 3 to 8, characterized in that, The specific steps of mixing the dehydrated oil phase with blueberry extract, grape seed extract, and carotene, and homogenizing the mixture to form a homogeneous slurry include: Carotene was added to the dehydrated oil phase and stirred to form a premixed oil phase; Blueberry extract and grape seed extract were premixed to obtain a solid extract complex; The premixed oil phase is transferred to a high-pressure homogenizer, and under inert gas protection, a solid extract complex is added multiple times. After each addition of the solid extract complex, homogenization is performed by applying pressure to form a homogeneous slurry.

10. The method for preparing the blueberry and grape seed lutein preparation for relieving eye fatigue as described in claim 9, characterized in that, The specific steps for homogenizing the material under pressure to form a homogeneous slurry include: After each homogenization process, the particle size distribution of the slurry was detected using an online laser particle size analyzer. If the particle size distribution of the slurry does not meet the homogenization conditions corresponding to the current homogenization treatment, the pressure parameters for the next homogenization treatment will be adjusted. Each homogenization treatment has different homogenization conditions. After the final homogenization process, a homogeneous slurry is formed.

Images