Igy gel beads and methods of making the same

Abstract

The present application relates to the technical field of medical gel beads, and specifically discloses an IgY gel bead and a preparation method thereof, which comprises the following components: 1-3.5 parts of sodium alginate, 0.5-10 parts of modified shellac, 0.5-1.5 parts of lecithin, 0.25-1.75 parts of IgY, 0.5-3 parts of a crosslinking agent, and an appropriate amount of water. The preparation method comprises the following steps: dissolving an appropriate amount of shellac powder in a Na2CO3 solution, and obtaining a modified shellac solution after water bath and stirring; mixing an appropriate amount of sodium alginate, lecithin and IgY with the modified shellac solution, and dissolving after water bath and stirring; standing for standby use; adding the mixed solution into a CaCl2 solution drop by drop while stirring, and continuously stirring until solidification after the addition is completed; and rinsing and drying the solidified substance to obtain the finished IgY gel bead. The present application has the characteristics of less active loss and better intestinal release effect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical gel beads, in particular to an Igy gel bead and a preparation method thereof. BACKGROUND

[0002] Immunoglobulin is a protein in egg yolk, which has multiple biological properties and is closely related to human health. However, protein drugs have the characteristics of large molecular weight and complex spatial structure, and are easily destroyed by the action of complex physiological environment, especially in a large number of enzymes. Therefore, when orally administered, the antigen-binding activity of IgY will be reduced or even completely lost due to the hydrolysis of gastric acid and pepsin, greatly reducing its biological effectiveness. In order to improve the bioavailability of orally administered IgY and resist the degradation of gastric acid and pepsin, further research is needed on how to properly protect the activity of IgY to enable it to function stably in the small intestine, and to provide a scientific theoretical basis for the development and utilization of IgY.

[0003] Chicken egg yolk immunoglobulin (Egg Yolk immunoglobulins, IgY) is a highly active oral antibody that can be used to protect and treat intestinal diseases caused by pathogens in the intestinal tract to achieve the effects of preventing and treating diseases and improving human immunity. It has the characteristics of simple preparation, low cost, high yield, safety, no toxicity, strong specificity, and no drug resistance, and is closely related to human health. Oral IgY can only be truly functional and active when it is absorbed and utilized by the human body. However, as a protein substance, oral IgY is very sensitive to pepsin and the low-pH environment of the stomach, and is easily lost in biological activity. Therefore, using microcapsule technology to embed it is one of the effective measures to maximize the retention of IgY biological activity and improve its stability.

[0004] The patent document with the publication number CN113975387A discloses a preparation method of anti-Helicobacter pylori yolk antibody embedding gel particles, the steps are as follows: first, the yolk antibody IgY is mixed with a preservative and the like to carry out emulsification reaction to obtain yolk antibody emulsion; taking gelatin and arabic gum as wall material, yolk antibody emulsion as core material, adding arabic gum solution and gelatin, adjusting pH value by hydrochloric acid, stirring to make the materials coagulate into microcapsules, then mixing the microcapsules with sodium alginate solution to form a mixed solution, slowly dropping the mixed solution into calcium chloride solution, then washing, drying to obtain; the gel bead particles in the patent document have high embedding rate, can improve the titer of antibodies, can reduce the loss rate of specific immunoglobulin activity in the stomach, and make the yolk antibody Igy gel bead particles in the gastrointestinal tract contain high activity, have sustained slow release effect, eradicate Helicobacter pylori in the gastrointestinal tract, thereby play a therapeutic role, do not produce side effects, and do not destroy intestinal flora. However, the stability of the IgY gel bead activity and the in vitro release effect in the gastrointestinal tract are still not ideal.

[0005] Meanwhile, specific preparation devices need to be used in the preparation process of the IgY gel bead. However, in the prior art, the existing preparation devices are too single in functionality, and can only simply stir and mix the raw materials required for preparing the IgY gel bead in the preparation process, the mixing efficiency is poor, and various needs in the preparation process of the IgY gel bead cannot be met, so that the quality of the prepared IgY gel bead is not uniform, and the standard requirements cannot be met. SUMMARY

[0006] In order to solve the above technical problems of the existing oral IgY, the present application provides an Igy gel bead with less activity loss and good intestinal release effect and a preparation method thereof.

[0007] The first technical scheme of the present application is an IgY gel bead, which comprises the following components by weight:

[0008] Sodium alginate 1-3.5 parts, modified shellac 0.5-10 parts, lecithin 0.5-1.5 parts, IgY 0.25-1.75 parts, crosslinking agent 0.5-3 parts, and appropriate amount of water. The present application selects appropriate parts of sodium alginate, modified shellac, lecithin, IgY and crosslinking agent as raw materials, wherein sodium alginate is used as the main wall material, shellac and lecithin are used as the composite wall material, and the crosslinking agent is used to prepare the IgY gel beads by the sharp hole-coagulation bath method, so that the IgY gel beads in the present application are finally obtained, so as to better reduce the activity loss of IgY in the stomach and make it reach the intestine to play a better effect; the present application adopts the shellac and sodium alginate to prepare the gel beads with the best performance after the IgY is embedded by the composite wall material, and the embedding rate and the drug loading capacity are used as indexes; the embedding by the composite wall material makes the embedding rate reach 85.49%, the drug loading capacity reaches 29.62%, the activity of IgY in the gel beads is 92%, the activity retention rate of IgY after gastric digestion is increased by 40%, and the activity loss rate is reduced; the various substances in the present application play a synergistic effect, can better embed IgY, so that IgY is not released in the stomach and is released only in the small intestine, and the activity loss before playing a role is less, and the release effect in the intestine is better.

[0009] As preferred, the following components are included by weight parts, sodium alginate 1.5-3 parts, modified shellac 2-8 parts, lecithin 0.7-1.2 parts, IgY 0.5-1.5 parts, crosslinking agent 1-2.5 parts, and appropriate amount of water.

[0010] As preferred, the following components are included by weight parts, sodium alginate 2-2.5 parts, modified shellac 4-6 parts, lecithin 0.9-1.1 parts, IgY 0.7-1.3 parts, crosslinking agent 1.5-2 parts, and appropriate amount of water.

[0011] As preferred, the following components are included by weight parts, sodium alginate 2.2 parts, modified shellac 5 parts, lecithin 1 part, IgY 1 part, crosslinking agent 1.8 parts, and appropriate amount of water.

[0012] As preferred, the crosslinking agent is anhydrous calcium chloride solution.

[0013] The second technical scheme of the present application is a preparation method of IgY gel beads, which comprises the following steps,

[0014] (S01) A proper amount of shellac powder is dissolved in a Na2CO3 solution through a feeding mechanism, then heated by a heating mechanism, and then mixed and stirred by a stirring mechanism and a mixing mechanism to obtain a modified shellac solution;

[0015] (S02) take the appropriate amount of sodium alginate, lecithin and IgY through the feeding mechanism and the modified shellac solution in step (S01) is mixed, and then heated by water bath heating mechanism, and then mixed and stirred by stirring mechanism and mixing mechanism, and then placed after dissolution, standby;

[0016] (S03) the mixed solution in step (S02) is added to the CaCl2 solution by the liquid adding mechanism and stirred by the stirring mechanism, and then continuously stirred and mixed by the stirring mechanism and the mixing mechanism after the addition is completed;

[0017] (S04) the solidified material after step (S03) is washed and dried by the cleaning mechanism, and the IgY gel bead finished product is prepared. The present application uses sodium alginate as the main wall material, shellac and lecithin as the composite wall material, and prepares the IgY gel bead by the sharp hole-coagulation bath method, which reduces the loss of activity of IgY in the stomach and makes it reach the intestine to play the effect; The performance of the IgY gel bead prepared by the composite wall material embedding IgY after the shellac and sodium alginate are compounded is the best. Taking the embedding rate and the drug loading as the index, the embedding rate reaches 85.49% and the drug loading reaches 29.62% after the composite wall material embedding, and the activity of IgY in the gel bead is 92%, which increases the retention rate of IgY activity after gastric digestion by 40% and reduces the activity loss rate. Through the microstructure observation, it is found that the overall structure of the gel bead particles is compact, and the swelling release experiment shows that IgY is not released in the stomach; through the SDS-PAGE gel electrophoresis analysis, it is found that the IgY gel bead prepared by the present application can detect IgY in the intestinal juice, but no IgY is detected in the gastric juice, which shows that the IgY gel bead is not digested in the stomach, but reaches the small intestine to release in vitro.

[0018] As preferred, in the step (S01), the water bath temperature is 55℃-65℃; the stirring time is 20min-40min.

[0019] As preferred, in the step (S02), the water bath temperature is 35℃-45℃; the stirring time is 20min-40min; the standing temperature is 22℃-28℃; the standing time is 8h-24h; the stirring speed is 200r / min-300r / min.

[0020] As preferred, the concentration of the Na2CO3 solution is 0.1mol / l; the mass concentration of the CaCl2 solution is 1.27%; the drop height is 10cm; the drop rate is 1ml / min-1.5ml / min.

[0021] Preferably, the drying is vacuum drying; the vacuum pressure of the vacuum drying is 500-700 MPa; the drying temperature of the vacuum drying is 35-45 DEG C; and the drying time of the vacuum drying is 20-28 hours.

[0022] The third technical scheme of the present application is a preparation device for IgY gel beads, comprising a base, a support plate fixedly installed on one side of the top of the base, a fixed plate arranged above the support plate, a preparation box arranged below the fixed plate and on one side of the support plate, a heating mechanism arranged in the preparation box, a stirring mechanism arranged in the heating mechanism, a cleaning mechanism arranged in the heating mechanism and on one side of the stirring mechanism, a feeding mechanism arranged above the heating mechanism and on one side of the stirring mechanism, a liquid adding mechanism fixedly arranged on the side of the preparation box away from the support plate, a mixing mechanism arranged on the side of the preparation box close to the support plate, and a driving mechanism arranged below the mixing mechanism. The water is heated to the required temperature by the heating mechanism, and the water is precisely heated, so that better preparation effect is achieved. The Na2CO3 solution and the shellac powder are mixed by the stirring mechanism, so that sufficient mixing effect is ensured. The impurities are cleaned by the cleaning mechanism, so that the quality of the final IgY gel bead product is ensured. The required shellac powder, sodium alginate, lecithin and IgY are quickly and smoothly added by the feeding mechanism. The degassed wall material and core material mixture to be added are smoothly and quickly added by the liquid adding mechanism. The mixing effect of the Na2CO3 solution and the shellac powder is improved by the mixing mechanism, and the mixing effect of the sodium alginate, lecithin and IgY and the modified shellac solution is also improved. The driving mechanism provides stable power for the operation of the whole device, so that stable operation of the whole preparation process is ensured.

[0023] As a preferred, the stirring mechanism comprises a motor, the motor is fixedly installed on the top of the fixed plate, the output end of the motor extends to the inside of the preparation box through the fixed plate, the output end of the motor is fixedly connected with a rotating plate, the bottom of the rotating plate is fixedly connected with a rotating rod, the outer side of the rotating rod is slidably connected with a sliding rod, the outer wall of the rotating rod is fixedly connected with a first sliding block on both sides, the inner wall of the sliding rod is symmetrically provided with a first sliding groove matched with the first sliding block, and the first sliding block and the first sliding groove are slidably connected. The inside of the sliding rod is fixedly connected with an inclined plate, a spring is arranged between the inclined plate and the rotating plate and on the outer side of the rotating rod, the inclined plate is slidably connected with the outer side of the rotating rod, the outer wall of the sliding rod is fixedly connected with a first stirring rod on both sides, two first stirring rods on the same side are fixedly connected with a second stirring rod, and two second stirring rods are fixedly connected. The top of the motor and on one side of the rotating plate is fixedly connected with a first push rod. Through the stirring mechanism, the output end of the motor drives the rotating plate to rotate, so that the rotating plate drives the rotating rod to rotate, the sliding rod drives the inclined plate to rotate, and then the stirring rod rotates to mix the Na2CO3 solution and the insect wax powder in the mixing box. When the high end of the inclined plate rotates away from the bottom of the first push rod, the inclined plate drives the sliding rod to move upward, so that the first sliding block slides upward in the first sliding groove, thereby driving the two stirring rods to move upward, and the mixing effect in the mixing box is improved.

[0024] As a preferred, the inside of the two second stirring rods is equally provided with a mounting groove, and the inside of the two mounting grooves is fixedly installed with a fan blade. The stirring rod rotates and drives the fan blade to move, and the fan blade rotates due to the pushing of the mixed fluid of the Na2CO3 solution and the insect wax powder, thereby further improving the mixing effect.

[0025] As a preferred, the mixing mechanism comprises a first gear, a first rotating shaft is rotatably connected to the bottom of the fixed plate and away from the motor, a second gear is fixedly connected to the outer side of the first rotating shaft, the first gear is fixedly connected to the outer side of the output end of the motor, the first gear is meshingly connected with the second gear, a third gear is fixedly connected to the outer side of the first rotating shaft and below the second gear, a gear ring is fixedly installed on the outer wall of the preparation box, the third gear is meshingly connected with the gear ring, a reinforcing seat is fixedly connected to the side of the support plate close to the preparation box, and the first rotating shaft is rotatably connected with the reinforcing seat. Through the mixing mechanism, the first gear drives the second gear to rotate, then the second gear drives the first rotating shaft to rotate, thereby the third gear rotates, the gear ring drives the preparation box to rotate, thereby facilitating further mixing of the Na2CO3 solution and the insect wax powder in the preparation box, and improving the mixing effect.

[0026] Preferably, the cleaning mechanism comprises a main water pipe, which is rotationally connected to the bottom of the preparation box, and two branch water pipes are symmetrically and fixedly connected to the inside of the main water pipe, and one end of each of the two branch water pipes is fixedly connected with a connecting pipe, and two spray heads are fixedly connected to the inside of the two connecting pipes at equal intervals, and the bottom end of the main water pipe extends into the inside of the base, and a rotary joint is connected to the bottom end of the main water pipe, and the end of the rotary joint away from the support plate is connected with a water inlet pipe, and a scraping assembly is arranged on the outside of the main water pipe and below the branch water pipes. By adding the cleaning mechanism, water flows from the inside of the water inlet pipe, and then flows into the inside of the branch water pipes and the connecting pipes in sequence through the main water pipe, and is sprayed out through the spray heads to clean the impurities inside the mixed box after preparation, thereby reducing the labor intensity of the workers and improving the cleaning effect.

[0027] Preferably, the scraping assembly comprises a horizontal plate, which is fixedly connected to the outside of the main water pipe and below the branch water pipes, and two scrapers are fixedly connected to the top of the horizontal plate. The horizontal plate rotates with the main water pipe, and then the two scrapers move to scrape the mixture remaining on the inner wall of the bottom of the preparation box, thereby reducing the waste caused by incomplete fishing.

[0028] Preferably, the driving mechanism comprises a first connecting seat, which is fixedly connected to the bottom end of the first rotating shaft, and the bottom of the first connecting seat is rotationally connected to the top of the base, and a connecting ring is rotationally connected to the outside of the first connecting seat, and a connecting rod is fixedly connected to the side of the connecting ring away from the support plate, and a second connecting seat is rotationally connected to one end of the connecting rod, and a first rack is fixedly connected to one end of the second connecting seat, and a fourth gear is fixedly connected to the outside of the main water pipe and between the base and the preparation box, and the fourth gear is in meshing connection with the first rack, and a limiting assembly is arranged at the bottom of the first rack. By adding the driving mechanism, the first connecting seat rotates with the first rotating shaft, and the connecting ring moves at the same time, and then the connecting rod pulls the first rack to move, so that the fourth gear rotates, which is conducive to driving the main water pipe to rotate through the fourth gear, thereby improving the cleaning efficiency of the inside of the mixed box.

[0029] Preferably, the limiting assembly comprises a second sliding block, which is fixedly connected to the bottom of the first rack, and a second sliding groove matched with the second sliding block is formed in the inside of the base and on one side of the rotary joint, and the second sliding block is in sliding connection with the inside of the second sliding groove. The first rack drives the second sliding block to slide in the second sliding groove during movement, which is conducive to limiting the movement track of the first rack, thereby improving the stability of the movement of the first rack.

[0030] As a preferred, the feeding mechanism comprises a feeding hopper, a feeding pipe is fixedly connected to the inside of the preparation box and located away from one side of the rotating plate, the feeding hopper is fixedly connected to the top of the feeding pipe, the inside of the feeding hopper is rotatably connected with a rotating box through a second rotating shaft, one end of one of the second rotating shafts extends to the outside of the feeding hopper, one end of one of the second rotating shafts is fixedly connected with a second rack, a first air cylinder is fixedly installed on the top of the preparation box and located at one side of the feeding hopper, the output end of the first air cylinder is fixedly connected with a second rack, the second rack is meshedly connected with a fifth gear, and the inside of the rotating box is provided with a weighing assembly. Through the feeding mechanism, the needed shellac powder is put into the inside of the rotating box, then the first air cylinder is started, the output end of the first air cylinder pushes the second rack to rotate, then the second rack drives the fifth gear to rotate, and the rotating box is turned over in the inside of the feeding hopper, which is favorable for the rapid discharging of the shellac powder in the inside of the rotating box.

[0031] As a preferred, the weighing assembly comprises a weighing plate, a pressure sensor is fixedly installed on the bottom of the inside of the feeding hopper, and the weighing plate is fixedly installed on the top of the pressure sensor and is in sliding connection with the inside of the feeding hopper. The shellac powder in the inside of the rotating box can extrude the weighing plate downwards, and the weight of the shellac powder in the inside of the rotating box can be rapidly detected through the pressure sensor, so that the weight of each time of adding raw materials is controlled, and the preparation precision is improved.

[0032] Preferably, the liquid adding mechanism comprises a liquid adding cylinder fixedly connected to the preparation box away from the support plate, a piston slidably connected inside the liquid adding cylinder, a second push rod fixedly connected to the top center of the piston, one end of the second push rod extending to the outside of the liquid adding cylinder, an installation plate fixedly connected to one end of the second push rod, an adjusting assembly provided on the top of the installation plate, a connecting strip fixedly connected to one end of the fixed plate close to the motor, a third push rod fixedly connected to the bottom of the connecting strip, a second spring sleeved between the piston and the liquid adding cylinder and outside the second push rod, a liquid inlet pipe fixedly connected to the side of the second spring away from the preparation box, a first electromagnetic valve fixedly connected inside the liquid inlet pipe, a liquid storage cylinder fixedly connected to the top end of the liquid inlet pipe, a reinforcing rod fixedly connected to the outside of the liquid inlet pipe, one end of the reinforcing rod fixedly connected to the outside of the liquid adding cylinder, air holes symmetrically provided on the top of the liquid adding cylinder, and a liquid delivery pipe fixedly connected to the bottom of the liquid adding cylinder. The liquid adding mechanism is used to put the degassed wall material and core material mixture to be added into the liquid storage cylinder, then open the first electromagnetic valve to make the degassed wall material and core material mixture in the liquid storage cylinder flow from the liquid inlet pipe to the inside of the liquid adding cylinder, then the liquid adding cylinder rotates below the connecting strip after the preparation box rotates, the third push rod pushes the adjusting plate to move downward to make the installation plate push the second push rod to move downward, then the piston moves downward to press the degassed wall material and core material mixture from the liquid delivery pipe to the inside of the mixing box, which is beneficial to automatically adding the degassed wall material and core material mixture into the mixing box.

[0033] Preferably, the adjusting assembly comprises a second air cylinder, the top edge of the installation plate is rotatably connected to an adjusting plate on one side, the second air cylinder is rotatably connected to the other side of the top edge of the installation plate, and the output end of the second air cylinder is rotatably connected to the bottom of the adjusting plate. The second air cylinder is started to push the adjusting plate to rotate around the installation plate, which is beneficial to adjusting the inclination angle of the adjusting plate and changing the amount of degassed wall material and core material mixture added each time.

[0034] Preferably, the heating mechanism comprises a mixing box fixedly connected to the inside of the preparation box, a water tank is formed in the inside of the mixing box, an electric heating wire is fixedly installed in the inside of the water tank, one end of the sliding rod and the rotating rod extends to the inside of the mixing box, the outside of the sliding rod is rotationally connected to the inside of the mixing box, the outside of the main water pipe is rotationally connected to the inside of the mixing box, one end of the main water pipe is rotationally connected to one end of the feeding pipe, a temperature sensor is fixedly installed on the top of the mixing box and on the side close to the supporting plate, a gas permeation pipe is fixedly connected to the inside of the mixing box and on the side of the temperature sensor, one end of the infusion pipe extends to the inside of the mixing box through the preparation box, one end of the infusion pipe is fixedly connected to the inside of the mixing box, one end of the feeding pipe extends to the inside of the mixing box, one end of the feeding pipe is fixedly connected to the inside of the mixing box, and a first discharging mechanism is arranged on the bottom of the mixing box. The water in the water tank can be heated by turning on the electric heating wire, and the temperature of the water in the water tank can be monitored in real time by the temperature sensor, so that the accuracy of heating the water is improved, and the preparation effect is not affected by different water temperatures.

[0035] Preferably, the first discharging mechanism comprises two first discharging pipes, and the two first discharging pipes are fixedly connected to the two sides of the bottom of the mixing box, and the inside of each of the two first discharging pipes is fixedly connected with a second electromagnetic valve.

[0036] Preferably, the bottom of the preparation box is provided with a second discharging mechanism, the second discharging mechanism comprises a second discharging pipe, the second discharging pipe is fixedly connected to the bottom of the preparation box, and the inside of the second discharging pipe is fixedly connected with a third electromagnetic valve.

[0037] Preferably, a material taking door is rotationally connected to the side of the gear ring on the outer wall of the preparation box, a control panel is fixedly installed on the upper side of the material taking door on the outer wall of the preparation box, and the third electromagnetic valve, the second electromagnetic valve, the electric heating wire, the second air cylinder, the first electromagnetic valve, the pressure sensor, the first air cylinder, the temperature sensor and the motor are electrically connected with the control panel. The control panel can be used for centralized control of various electrical devices, so that the operation time of the workers is reduced, and the operation efficiency of the workers is improved.

[0038] The present application has the following advantages:

[0039] (1) The present application uses appropriate amounts of sodium alginate, modified shellac, lecithin, IgY and a crosslinking agent as raw materials, wherein the sodium alginate is used as a main wall material, the shellac and the lecithin are used as a composite wall material, the crosslinking agent is used to prepare gel beads embedding IgY through a sharp hole-coagulation bath method, and finally the IgY gel beads in the present application are obtained, so as to better reduce the loss of activity of IgY in the stomach and make the IgY reach the intestine to play a better effect.

[0040] (2) The performance of the gel beads prepared by embedding IgY with the compound wall material of shellac and sodium alginate is the best. Taking embedding rate and drug loading as indexes, the embedding rate reaches 85.49% and the drug loading reaches 29.62% after embedding with the compound wall material, the activity of IgY in the gel beads is 92%, the activity retention rate of IgY after gastric digestion is increased by 40%, and the activity loss rate is reduced;

[0041] (3) It is found through microstructure observation that the overall structure of the gel bead particles is compact, and it is found through swelling release experiment that IgY is not released in the stomach. It is found through SDS-PAGE gel electrophoresis analysis that the gel beads prepared in the application can detect IgY in intestinal juice, but no IgY is detected in gastric juice, which shows that the IgY gel beads are not digested in the stomach, but reach the small intestine to release in vitro;

[0042] (4) Various substances play a synergistic role to better embed IgY, so that IgY is not released in the stomach and is released only in the small intestine, and the activity loss before playing a role is less, and the release effect in the intestinal tract is better;

[0043] (5) The heating mechanism is arranged to heat water to the required temperature, so that the water can be accurately heated, thereby achieving better preparation effect; the stirring mechanism is arranged to mix Na2CO3 solution and shellac powder, so as to ensure sufficient mixing effect; the cleaning mechanism is arranged to clean impurities, so as to ensure the quality of the final IgY gel bead product; the feeding mechanism is arranged to quickly and smoothly add the required shellac powder, sodium alginate, lecithin and IgY; the liquid adding mechanism is arranged to smoothly and quickly add the degassed wall material and core material mixture; the mixing mechanism is arranged to improve the mixing effect of Na2CO3 solution and shellac powder, and also improve the mixing effect of sodium alginate, lecithin and IgY and the modified shellac solution; the driving mechanism is arranged to provide stable power for the operation of the whole equipment, so as to ensure the stable operation of the whole preparation process. BRIEF DESCRIPTION OF DRAWINGS

[0044] Figure 1 It is a structure schematic diagram of the equipment in the application;

[0045] Figure 2 It is a cross-sectional structure schematic diagram of the equipment in the application;

[0046] Figure 3 It is a structure schematic diagram of the stirring mechanism in the application;

[0047] Figure 4 It is a structure schematic diagram of the driving mechanism in the application;

[0048] Figure 5Structure diagram of the second stirring rod in the application;

[0049] Figure 6 Structure diagram of the scraping assembly in the application;

[0050] Figure 7 Structure diagram of the adjusting assembly in the application;

[0051] Figure 8 Structure diagram of the A part in the application Figure 2 Structure diagram of the B part in the application

[0052] Figure 9 Structure diagram of the C part in the application Figure 2 Structure diagram of the D part in the application

[0053] Figure 10 Structure diagram of the E part in the application Figure 2

[0054] Figure 11 Figure 2

[0055] Figure 12 Figure 2

[0056] Figure 13 Effect of the sodium alginate concentration in the single wall material embedding IgY on the embedding effect of the gel beads in the application;

[0057] Figure 14 Effect of CaCl2 in the single wall material embedding IgY on the embedding effect of the gel beads in the application;

[0058] Figure 15 Effect of the core-wall ratio in the single wall material embedding IgY on the embedding effect of the gel beads in the application;

[0059] Figure 16 Swelling curve of the gel bead particles with different sodium alginate concentrations in the single wall material embedding IgY in the application;

[0060] Figure 17 Swelling curve of the gel bead particles with different CaCl2 concentrations in the single wall material embedding IgY in the application;

[0061] Figure 18 Swelling curve of the gel bead particles with different core-wall ratios in the single wall material embedding IgY in the application;

[0062] Figure 19 In vitro release diagram of the gel bead particles with different sodium alginate concentrations in the single wall material embedding IgY in the application;

[0063] Figure 20 ​​​​​In vitro release profile of gel beads with different calcium chloride concentrations embedded in a single wall material for the present invention;

[0064] Figure 21 In vitro release profile of gel beads with different core-to-wall ratios embedded in a single wall material for the present invention;

[0065] Figure 22 Effect of different shellac concentrations on the embedding effect of gel beads embedded in a composite wall material for the present invention;

[0066] Figure 23 SEM images of IgY-calcium alginate gel beads (a 80, b 1500) and IgY-calcium alginate-shellac- lecithin gel beads (c 80, d 1500) for the present invention;

[0067] Figure 24 Effect of different shellac concentrations on the swelling degree of gel beads embedded in a composite wall material for the present invention;

[0068] Figure 25 In vitro release profile of gel beads with different shellac concentrations embedded in a composite wall material for the present invention.

[0069] Marked in the drawings: 100-base; 200-supporting plate; 300-fixing plate; 400-preparation box; 500-stirring mechanism; 501-motor; 502-rotating rod; 503-rotating plate; 504-first spring; 505-inclined plate; 506-first push rod; 507-sliding rod; 508-first sliding groove; 509-first sliding block; 510-first stirring rod; 511-second stirring rod; 512-mounting groove; 513-fan blade; 600-mixing mechanism; 601-first gear; 602-second gear; 603-first rotating shaft; 604-third gear; 605-toothed ring; 700-driving mechanism; 701-first connecting seat; 702-connecting ring; 703-connecting rod; 704-second connecting seat; 705-first rack; 706-fourth gear; 800-cleaning mechanism; 801-main water pipe; 802-branch water pipe; 803-connecting pipe; 804-sprayer; 805-rotary joint; 806-water inlet pipe; 900-feeding mechanism; 901-feeding hopper; 902-feeding pipe; 903-first air cylinder; 904-second rack; 905-fifth gear; 906-rotating box; 907-second rotating shaft; 1000-weighing assembly; 1001-weighing plate; 1002-pressure sensor; 1100-liquid adding mechanism; 1101-liquid adding cylinder; 1102-piston; 1103-second push rod; 1104-mounting plate; 1105-connecting strip; 1106-third push rod; 1107-liquid storage cylinder; 1108-liquid inlet pipe; 1109-first electromagnetic valve; 1110-second spring; 1111-air permeation hole; 1112-strengthening rod; 1200-adjusting assembly; 1201-second air cylinder; 1202-adjusting plate; 1300-scraping assembly; 1301-cross plate; 1302-scraping plate; 1400-first discharging mechanism; 1401-first discharging pipe; 1402-second electromagnetic valve; 1500-heating mechanism; 1501-mixing box; 1502-water tank; 1503-electric heating wire; 1600-second discharging mechanism; 1601-second discharging pipe; 1602-third electromagnetic valve; 1700-limiting assembly; 1701-second sliding block; 1702-second sliding groove; 1800-temperature sensor; 1900-air permeation pipe; 2000-strengthening seat; 2100-control panel; 2200-material taking door. DETAILED DESCRIPTION

[0070] The application will be further described in conjunction with the embodiments and drawings, but it is not as the basis for limiting the application.

[0071] An IgY gel bead comprises the following components by weight parts,

[0072] Sodium alginate 1-3.5 parts, modified shellac 0.5-10 parts, lecithin 0.5-1.5 parts, IgY 0.25-1.75 parts, crosslinking agent 0.5-3 parts, and appropriate amount of water.

[0073] An IgY gel bead comprises the following components by weight parts,

[0074] Sodium alginate 1.5-3 parts, modified shellac 2-8 parts, lecithin 0.7-1.2 parts, IgY 0.5-1.5 parts, crosslinking agent 1-2.5 parts, and appropriate amount of water.

[0075] An IgY gel bead comprises the following components by weight parts,

[0076] Sodium alginate 2-2.5 parts, modified shellac 4-6 parts, lecithin 0.9-1.1 parts, IgY 0.7-1.3 parts, crosslinking agent 1.5-2 parts, and appropriate amount of water.

[0077] An IgY gel bead comprises the following components by weight parts, sodium alginate 2.2 parts, modified shellac 5 parts, lecithin 1 part, IgY 1 part, crosslinking agent 1.8 parts, and appropriate amount of water.

[0078] The crosslinking agent is anhydrous calcium chloride solution.

[0079] A preparation method of an IgY gel bead comprises the following steps,

[0080] (S01) A proper amount of shellac powder is dissolved in a Na2CO3 solution through a feeding mechanism 900, and then heated through a heating mechanism 1500 water bath, and then stirred through a stirring mechanism 500 and a mixing mechanism 600 to obtain a modified shellac solution; the water bath temperature is 55-65°C; the stirring time is 20-40 min; the concentration of the Na2CO3 solution is 0.1 mol / l;

[0081] (S02) Then, the proper amount of sodium alginate, lecithin and IgY are mixed with the modified shellac solution in step (S01), and then heated through a heating mechanism 1500 water bath, and then stirred through a stirring mechanism 500 and a mixing mechanism 600 until dissolved, and then placed for standby; the water bath temperature is 35-45°C; the stirring time is 20-40 min; the standing temperature is 22-28°C; the standing time is 8-24 h; the stirring speed is 200-300 r / min;

[0082] (S03) the mixed solution in step (S02) is added dropwise through the liquid adding mechanism 1100 and stirred through the stirring mechanism 500 into the CaCl2 solution, after the dropwise addition is completed, the stirring and mixing are continuously carried out through the stirring mechanism 500 and the mixing mechanism 600 until solidification; the mass concentration of the CaCl2 solution is 1.27%; the dropwise addition height is 10 cm; the dropwise addition rate is 1 ml / min~1.5 ml / min;

[0083] (S04) the solidified substance after step (S03) is washed through the cleaning mechanism 800 and dried to obtain the IgY gel bead finished product; the drying is vacuum drying; the vacuum pressure of the vacuum drying is 500 MPa~700 MPa; the drying temperature of the vacuum drying is 35℃~45℃; the drying time of the vacuum drying is 20 h~28 h.

[0084] As shown in Figure 1 and Figure 2 , a preparation equipment for IgY gel beads comprises a base 100, a supporting plate 200 and a fixed plate 300, the top side of the base 100 is fixedly installed with the supporting plate 200, the upper side of the supporting plate 200 is provided with the fixed plate 300, the lower side of the fixed plate 300 and the side of the supporting plate 200 are provided with a preparation box 400, the inside of the preparation box 400 is provided with a heating mechanism 1500, the inside of the preparation box 400 and the lower side of the heating mechanism 1500 are provided with a scraping assembly 1300, the inside of the heating mechanism 1500 is provided with a stirring mechanism 500, the inside of the heating mechanism 1500 and the side of the stirring mechanism 500 are provided with a cleaning mechanism 800, the upper side of the heating mechanism 1500 and the side of the stirring mechanism 500 are provided with a feeding mechanism 900, the side, away from the supporting plate 200, of the preparation box 400 is fixedly provided with a liquid adding mechanism 1100, the side, close to the supporting plate 200, of the preparation box 400 is provided with a mixing mechanism 600, and the lower side of the mixing mechanism 600 is provided with a driving mechanism 700.

[0085] The stirring mechanism 500 comprises a motor 501, the top of the fixed plate 300 is fixedly installed with the motor 501, the output end of the motor 501 penetrates through the fixed plate 300 and is fixedly connected with a rotating plate 503 extending to the inside of the preparation box 400, the bottom of the rotating plate 503 is fixedly connected with a rotating rod 502, the outer side of the rotating rod 502 is slidably connected with a sliding rod 507 as shown in Figure 3 , the outer wall of the rotating rod 502 is symmetrically fixedly connected with a first sliding block 509 as shown in Figure 10 , the inner wall of the sliding rod 507 is symmetrically provided with a first sliding groove 508 matched with the first sliding block 509, and the first sliding block 509 and the first sliding groove 508 are slidably connected, the top of the sliding rod 507 is fixedly connected with an inclined plate 505, the inclined plate 505 and the rotating plate 503 are sleeved with a second sliding block 506 as shown in Figure 8The shown No. 1 spring 504, the inclined plate 505 and the outer side of the rotating rod 502 are slidingly connected, and the outer wall of the sliding rod 507 is symmetrically fixedly connected with two No. 1 stirring rods 510 Figure 5 The shown No. 1 stirring rod 510, the two No. 1 stirring rods 510 on the same side are fixedly connected with two No. 2 stirring rods 511, and the two No. 2 stirring rods 511 are fixedly connected. The top of the motor 501 and one side of the rotating plate 503 are fixedly connected with a No. 1 push rod 506;

[0086] The two No. 2 stirring rods 511 are equally spaced to form installation grooves 512 in the interiors thereof, and two installation grooves 512 are fixedly installed with Figure 9 The shown fan blade 513;

[0087] Through the stirring mechanism 500, the output end of the motor 501 drives the rotating plate 503 to rotate, so that the rotating plate 503 drives the rotating rod 502 to rotate, so that the sliding rod 507 drives the inclined plate 505 to rotate, and then the two No. 2 stirring rods 511 rotate to mix the Na2CO3 solution and the insect wax powder in the mixing box 1501. When the high end of the inclined plate 505 rotates away from the bottom of the No. 1 push rod 506, the inclined plate 505 drives the sliding rod 507 to move upward, so that the No. 1 sliding block 509 slides upward in the No. 1 sliding groove 508, thereby driving the two No. 2 stirring rods 511 to move upward, increasing the mixing effect in the mixing box 1501. At the same time, the No. 2 stirring rod 511 rotates to drive the fan blade 513 to move. The fan blade 513 rotates due to the pushing of the mixed fluid of the Na2CO3 solution and the insect wax powder, further improving the mixing effect.

[0088] The mixing mechanism 600 includes a No. 1 gear 601, a No. 1 rotating shaft 603 rotatably connected to the bottom of the fixed plate 300 and away from the motor 501, a No. 2 gear 602 fixedly connected to the outer side of the No. 1 rotating shaft 603, a No. 1 gear 601 fixedly connected to the outer side of the output end of the motor 501, the No. 1 gear 601 and the No. 2 gear 602 are meshingly connected, a No. 3 gear 604 fixedly connected to the outer side of the No. 1 rotating shaft 603 and below the No. 2 gear 602, a gear ring 605 fixedly installed on the outer wall of the preparation box 400, the No. 3 gear 604 and the gear ring 605 are meshingly connected, a reinforcing seat 2000 fixedly connected to the side of the support plate 200 close to the preparation box 400, and the No. 1 rotating shaft 603 is rotatably connected to the interior of the reinforcing seat 2000.

[0089] Through the mixing mechanism 600, the No. 1 gear 601 drives the No. 2 gear 602 to rotate, and then the No. 2 gear 602 drives the No. 1 rotating shaft 603 to rotate, so that the No. 3 gear 604 rotates, and the gear ring 605 drives the preparation box 400 to rotate, thereby facilitating further mixing of the Na2CO3 solution and the insect wax powder in the preparation box 400, and improving the mixing effect.

[0090] The cleaning mechanism 800 includes a main water pipe 801 and a scraping assembly 1300. The main water pipe 801 is rotatably connected to the bottom of the preparation box 400. The main water pipe 801 is symmetrically fixed to both sides of the inside of the main water pipe 801. One end of each of the two branch water pipes 802 is fixedly connected to a connecting pipe 803. The inside of each of the two connecting pipes 803 is fixedly connected to a nozzle 804 at equal intervals. The bottom end of the main water pipe 801 extends into the inside of the base 100 and is connected to a rotary joint 805. The end of the rotary joint 805 away from the support plate 200 is connected to a water inlet pipe 806. The scraping assembly 1300 is arranged on the outside of the main water pipe 801 and below the branch water pipes 802.

[0091] Scraping component 1300 includes, for example Figure 6 The horizontal plate 1301 shown is fixedly connected to the outside of the main water pipe 801 and below the branch water pipe 802. Scrapers 1302 are symmetrically fixedly connected to the top two sides of the horizontal plate 1301.

[0092] By adding a cleaning mechanism 800, water flows in from the inside of the inlet pipe 806, and then flows from the main water pipe 801 to the inside of the branch pipe 802 and the connecting pipe 803. The water is then sprayed out by the nozzle 804 to clean the impurities inside the prepared mixing tank 1501, thereby reducing the labor intensity of the workers and improving the cleaning effect. At the same time, the horizontal plate 1301 will rotate with the main water pipe 801, and then the two scrapers 1302 will follow the movement to scrape off the residual mixture on the inner wall of the bottom of the preparation tank 400, reducing the waste caused by incomplete retrieval.

[0093] The drive mechanism 700 includes a first connecting seat 701 and a limiting assembly 1700. The bottom end of the first rotating shaft 603 is fixedly connected to the first connecting seat 701. The bottom of the first connecting seat 701 is rotatably connected to the top of the base 100. A connecting ring 702 is rotatably connected to the outer side of the first connecting seat 701. A connecting rod 703 is fixedly connected to the side of the connecting ring 702 away from the support plate 200. A second connecting seat 704 is rotatably connected to one end of the connecting rod 703. One end of the second connecting seat 704 is fixedly connected to... Figure 4 The rack 705 shown is fixedly connected to the fourth gear 706 on the outside of the main water pipe 801 and between the base 100 and the preparation box 400. The fourth gear 706 meshes with the rack 705. A limit component 1700 is provided at the bottom of the rack 705.

[0094] The limiting assembly 1700 comprises a second sliding block 1701, the bottom of the first rack 705 is fixedly connected with the second sliding block 1701, the inside of the base 100 and located at one side of the rotary joint 805 is provided with a second sliding groove 1702 matched with the second sliding block 1701, and the second sliding block 1701 and the inside of the second sliding groove 1702 are in sliding connection;

[0095] By adding the driving mechanism 700, the first connecting seat 701 rotates with the first rotating shaft 603, and the connecting ring 702 is pulled to follow the movement, and then the connecting rod 703 pulls the first rack 705 to follow the movement, so that the fourth gear 706 rotates, which is beneficial to make the fourth gear 706 drive the main water pipe 801 to rotate, thereby improving the cleaning efficiency of the inside of the mixing box 1501, and the first rack 705 will drive the second sliding block 1701 to slide in the inside of the second sliding groove 1702 in the movement process, which is beneficial to limit the movement track of the first rack 705, thereby improving the stability of the movement of the first rack 705;

[0096] The feeding mechanism 900 comprises a feeding hopper 901 and a weighing assembly 1000, the inside of the preparation box 400 and located away from one side of the rotating plate 503 is fixedly connected with a feeding pipe 902, the top of the feeding pipe 902 is fixedly connected with the feeding hopper 901, the inside of the feeding hopper 901 is rotatably connected with a rotating box 906 as shown in Figure 12 , one end of the second rotating shaft 907 extending to the outside of the feeding hopper 901 is fixedly connected with the second rack 904, the top of the preparation box 400 and located at one side of the feeding hopper 901 is fixedly installed with a first air cylinder 903, the output end of the first air cylinder 903 is fixedly connected with the second rack 904, the second rack 904 is in meshing connection with the fifth gear 905 as shown in Figure 12 , and the inside of the rotating box 906 is provided with the weighing assembly 1000;

[0097] The weighing assembly 1000 comprises a weighing plate 1001, the bottom of the inside of the feeding hopper 901 is fixedly installed with a pressure sensor 1002, the top of the pressure sensor 1002 is fixedly installed with the weighing plate 1001, and the weighing plate 1001 is in sliding connection with the inside of the feeding hopper 901;

[0098] The shellac powder is put into the inside of the rotating box 906 through the feeding mechanism 900, and then the first air cylinder 903 is started, the output end of the first air cylinder 903 drives the second rack 904 to rotate, and then the second rack 904 drives the fifth gear 905 to rotate, so that the rotating box 906 is turned over in the inside of the feeding hopper 901, which is beneficial to the rapid discharging of the shellac powder in the inside of the rotating box 906, and the shellac powder in the inside of the rotating box 906 can be extruded to the weighing plate 1001, and then the weight of the raw material in the inside of the rotating box 906 can be quickly detected through the pressure sensor 1002, so that the weight of the shellac powder added each time is controlled, and the preparation accuracy is improved.

[0099] The liquid adding mechanism 1100 comprises a liquid adding cylinder 1101 and an adjusting assembly 1200, and the liquid adding cylinder 1101 is fixedly connected to the side, away from the supporting plate 200, of the preparation box 400. The inside of the liquid adding cylinder 1101 is slidably connected with a piston 1102, the top center of the piston 1102 is fixedly connected with a second push rod 1103, one end of the second push rod 1103 extends to the outside of the liquid adding cylinder 1101 and is fixedly connected with a mounting plate 1104, and the mounting plate 1104 is provided with the adjusting assembly 1200 at the top. The end, close to the motor 501, of the fixed plate 300 is fixedly connected with a connecting strip 1105, and the bottom of the connecting strip 1105 is fixedly connected with a third push rod 1106. A second spring 1110 as shown in the figure is arranged between the piston 1102 and the liquid adding cylinder 1101 and outside the second push rod 1103. Figure 11 The side, away from the preparation box 400, of the second spring 1110 is fixedly connected with a liquid inlet pipe 1108, the inside of the liquid inlet pipe 1108 is fixedly connected with a first electromagnetic valve 1109, the top end of the liquid inlet pipe 1108 is fixedly connected with a liquid storage cylinder 1107, the outside of the liquid inlet pipe 1108 is fixedly connected with a reinforcing rod 1112, one end of the reinforcing rod 1112 is fixedly connected with the outside of the liquid adding cylinder 1101, and the top of the liquid adding cylinder 1101 is symmetrically provided with air holes 1111 at both sides, and the bottom of the liquid adding cylinder 1101 is fixedly connected with a liquid outlet pipe.

[0100] The adjusting assembly 1200 comprises a second air cylinder 1201, the top edge of the mounting plate 1104 is rotatably connected with an adjusting plate 1202 at one side, and the top edge of the mounting plate 1104 is rotatably connected with the second air cylinder 1201 at the other side as shown in the figure. Figure 7 The output end of the second air cylinder 1201 is rotatably connected with the bottom of the adjusting plate 1202.

[0101] The degassed wall material and core material mixture to be added is placed into the storage cylinder 1107 through the liquid addition mechanism 1100. Then, the first solenoid valve 1109 is opened, allowing the degassed wall material and core material mixture inside the storage cylinder 1107 to flow from the inlet pipe 1108 into the liquid addition cylinder 1101. After the liquid addition cylinder 1101 rotates with the preparation box 400 to below the connecting bar 1105, the third push rod 1106 will push the adjusting plate 1202 downward, causing the mounting plate 1104 to push the second push rod 1103 and... As the piston 1102 moves downward, it presses the degassed wall material and core material mixture from the infusion tube into the mixing tank 1501. This facilitates the automatic addition of the degassed wall material and core material mixture into the mixing tank 1501. At the same time, by activating the second cylinder 1201, the output end of the second cylinder 1201 pushes the adjusting plate 1202 to rotate around the mounting plate 1104. This facilitates the adjustment of the tilt angle of the adjusting plate 1202, thereby changing the amount of wall material and core material mixture added each time.

[0102] The heating mechanism 1500 includes a mixing tank 1501 and a first discharge mechanism 1400. The mixing tank 1501 is fixedly connected inside the preparation tank 400. A water tank 1502 is provided inside the mixing tank 1501. A certain type of heating device is fixedly installed inside the water tank 1502. Figure 8 The heating wire 1503 shown, one end of the sliding rod 507 and the rotating rod 502 all extend into the interior of the mixing box 1501, and the outer side of the sliding rod 507 is rotatably connected to the interior of the mixing box 1501. The outer side of the main water pipe 801 is rotatably connected to the interior of the mixing box 1501, and one end of the main water pipe 801 is rotatably connected to one end of the feed pipe 902. A temperature sensor 1800 is fixedly installed on the top of the mixing box 1501 and on the side near the support plate 200. A vent pipe 1900 is fixedly connected inside the mixing box 1501 and on the side of the temperature sensor 1800. One end of the infusion pipe passes through the preparation box 400 and extends into the interior of the mixing box 1501 and is fixedly connected to the interior of the mixing box 1501. One end of the feed pipe 902 extends into the interior of the mixing box 1501 and is fixedly connected to the interior of the mixing box 1501. A discharge mechanism 1400 is provided at the bottom of the mixing box 1501.

[0103] The first discharge mechanism 1400 includes a first discharge pipe 1401. The bottom sides of the mixing box 1501 are symmetrically and fixedly connected to the first discharge pipe 1401. The two first discharge pipes 1401 are fixedly connected to the inside of the two first discharge pipes 1401. The second solenoid valve 1402 can be opened to discharge the waste liquid after cleaning inside the mixing box 1501.

[0104] The water inside the water tank 1502 can be heated by opening the electric heating wire 1503, so that the water inside the water tank 1502 is heated to the required temperature, and the temperature of the water inside the water tank 1502 can be monitored in real time through the temperature sensor 1800, which is beneficial to improve the accuracy of water heating and prevent the water temperature from affecting the preparation effect;

[0105] The bottom of the preparation box 400 is provided with a second discharging mechanism 1600.

[0106] The second discharging mechanism 1600 comprises a second discharging pipe 1601, the bottom of the preparation box 400 is fixedly connected with the second discharging pipe 1601, the inside of the second discharging pipe 1601 is fixedly connected with a third electromagnetic valve 1602, and the waste liquid cleaned in the preparation box 400 can be discharged by opening the third electromagnetic valve 1602.

[0107] The outer wall of the preparation box 400 and located on one side of the gear ring 605 is rotatably connected with a material taking door 2200 as shown in the drawing. Figure 1 The material taking door 2200 can be opened to take out the mixture of the wall material and the core material after degassing after preparation for standby, the outer wall of the preparation box 400 and located above the material taking door 2200 is fixedly installed with a control panel 2100, the third electromagnetic valve 1602, the second electromagnetic valve 1402, the electric heating wire 1503, the second air cylinder 1201, the first electromagnetic valve 1109, the pressure sensor 1002, the first air cylinder 903, the temperature sensor 1800 and the motor 501 are all electrically connected with the control panel 2100.

[0108] The working principle of the present application is as follows:

[0109] Put the device to the desired preparation site and connect the power supply. First, start the No. 1 air cylinder 903 through the control panel 2100, and then the output end of the No. 1 air cylinder 903 pushes the No. 2 rack 904 to rotate, and then the No. 2 rack 904 drives the No. 5 gear 905 to rotate, so that the rotating box 906 is turned over inside the feeding hopper 901. Then inject the Na2CO3 solution into the inside of the mixing box 1501 from the feeding pipe 902, and then start the No. 1 air cylinder 903 to reset the rotating box 906 inside the feeding hopper 901. Then put the shellac powder into the inside of the rotating box 906, and then start the No. 1 air cylinder 903 through the control panel 2100, and then the output end of the No. 1 air cylinder 903 pushes the No. 2 rack 904 to rotate, and then the No. 2 rack 904 drives the No. 5 gear 905 to rotate, so that the rotating box 906 is turned over inside the feeding hopper 901. It is beneficial to quickly discharge the shellac powder in the rotating box 906, and at the same time the shellac powder in the rotating box 906 can extrude the weighing plate 1001 downward, and then the weight of the shellac powder in the rotating box 906 can be quickly detected through the pressure sensor 1002, thereby controlling the weight of the shellac powder added each time, improving the accuracy of preparation. The weighed shellac powder enters the inside of the mixing box 1501 through the feeding pipe 902 and fuses with the Na2CO3 solution. Before mixing, the water in the water tank 1502 can be heated to 60℃ by turning on the heating wire 1503, and the temperature of the water in the water tank 1502 can be monitored in real time through the temperature sensor 1800, which is beneficial to improve the accuracy of water heating and prevent different water temperatures from affecting the preparation effect. Then start the motor 501 through the control panel 2100, and the output end of the motor 501 drives the rotating plate 503 to rotate, thereby driving the rotating rod 502 to rotate, and the sliding rod 507 drives the inclined plate 505 to rotate, and then the two No. 2 stirring rods 511 rotate to mix the Na2CO3 solution and the shellac powder in the mixing box 1501. At the same time, when the high end of the inclined plate 505 rotates away from the bottom of the No. 1 push rod 506, the inclined plate 505 drives the sliding rod 507 to move upward, so that the No. 1 sliding block 509 slides upward in the No. 1 sliding groove 508, thereby driving the two No. 2 stirring rods 511 to move upward, increasing the mixing effect in the mixing box 1501. At the same time, the No. 2 stirring rod 511 rotates and drives the fan blade 513 to move. The fan blade 513 rotates due to the pushing of the mixed fluid of the Na2CO3 solution and the shellac powder, further improving the mixing effect. At the same time, the No. 1 gear 601 drives the No. 2 gear 602 to rotate, and then the No. 2 gear 602 drives the No. 1 rotating shaft 603 to rotate, thereby driving the No. 3 gear 604 to rotate, and the gear ring 605 drives the preparation box 400 to rotate, thereby facilitating further mixing of the mixed liquid in the preparation box 400. When the mixing time reaches 30 min, the modified shellac solution can be obtained. Then wait until the water in the water tank 1502 cools down to 40℃,The core material IgY and the wall material sodium alginate and the wall material lecithin are weighed and added to the modified shellac solution, stirred for 30 min, until the sodium alginate, lecithin and IgY are completely dissolved, then stop stirring and let the wall material and core material mixture stand overnight, degas through the breather pipe 1900, then open the second electromagnetic valve 1402, and the degassed wall material and core material mixture flows out from the inside of the first discharge pipe 1401, then open the material door 2200 to take out the degassed wall material and core material mixture for standby, connect the water inlet pipe 806 to the external water source pipe, water flows into the inside of the water inlet pipe 806, then flows into the inside of the main water pipe 801, the branch pipe 802 and the connecting pipe 803 in turn, and is sprayed out by the spray head 804 to clean the impurities in the prepared mixing box 1501, at the same time, start the motor 501 through the control panel 2100, the first gear 601 drives the second gear 602 to rotate, then the second gear 602 drives the first rotating shaft 603 to rotate, the first rotating shaft 603 rotates to drive the first connecting seat 701 to rotate with the first rotating shaft 603, and the connecting ring 702 follows the movement, then the connecting rod 703 pulls the first rack 705 to follow the movement, so that the fourth gear 706 rotates, when the first connecting seat 701 rotates half a turn, the connecting rod 703 pushes the first rack 705 to drive the fourth gear 706 to rotate in the opposite direction, which is conducive to making the fourth gear 706 drive the main water pipe 801 to reciprocate, thereby improving the cleaning efficiency of the inside of the mixing box 1501, at the same time, the first rack 705 drives the second sliding block 1701 to slide in the second sliding groove 1702 during movement, which is conducive to limiting the movement track of the first rack 705, thereby improving the stability of the movement of the first rack 705, the waste water flows out through the first discharge pipe 1401 and the second discharge pipe 1601, then the CaCl2 solution is injected into the inside of the mixing box 1501 by adding Na2CO3 solution, then the degassed wall material and core material mixture is placed in the liquid storage cylinder 1107, then the first electromagnetic valve 1109 is opened to make the degassed wall material and core material mixture in the liquid storage cylinder 1107 flow into the liquid adding cylinder 1101 through the liquid inlet pipe 1108, then the liquid adding cylinder 1101 rotates to the lower side of the connecting strip 1105 with the preparation box 400, the third push rod 1106 pushes the adjusting plate 1202 to move downward to make the mounting plate 1104 push the second push rod 1103 to move downward, then the piston 1102 moves downward to press the additive from the infusion tube into the inside of the mixing box 1501, which is conducive to automatically adding the degassed wall material and core material mixture to the inside of the mixing box 1501, at the same time, the second air cylinder 1201 is started to make the output end of the second air cylinder 1201 push the adjusting plate 1202 to rotate around the mounting plate 1104, which is conducive to adjusting the inclination angle of the adjusting plate 1202, thereby changing the amount of degassed wall material and core material mixture added each time, then the motor 501 is started through the control panel 2100,The mixture of the degassed wall material and core material and the CaCl2 solution are stirred for 30 minutes, then the stirring is stopped, the second electromagnetic valve 1402 is opened, the mixture obtained after stirring flows from the inside of the first discharge pipe 1401 to the bottom of the inside of the preparation box 400, solidifies, after preparation, the material door 2200 is opened, the solidified gel beads are fished out, rinsed with distilled water, dried, and the IgY gel bead finished product is obtained, then the motor 501 is started to clean the preparation box 400 again, and the cross plate 1301 rotates with the main water pipe 801, then the two scrapers 1302 follow the movement, and the mixture remaining on the inner wall of the bottom of the preparation box 400 is scraped off, reducing waste caused by incomplete fishing.

[0110] Example 1:

[0111] An IgY gel bead, comprising the following components by weight parts,

[0112] 1 part of sodium alginate, 0.5 parts of modified shellac, 0.5 parts of lecithin, 0.25 parts of IgY, 0.5 parts of crosslinking agent, and appropriate amount of water.

[0113] A preparation method of an IgY gel bead, comprising the following steps,

[0114] (S01) A suitable amount of shellac powder is dissolved in a 0.1 mol / l Na2CO3 solution through the feeding mechanism 90, then heated in a 60℃ water bath through the heating mechanism 1500, and then mixed and stirred through the stirring mechanism 500 and the mixing mechanism 600 to obtain a modified shellac solution; the stirring time is 30 minutes; the stirring speed is 250r / min;

[0115] (S02) A suitable amount of sodium alginate, lecithin and IgY are mixed with the modified shellac solution in step (S01) through the feeding mechanism 900, then heated in a 40℃ water bath through the heating mechanism 1500, and then mixed and stirred until dissolved through the stirring mechanism 500 and the mixing mechanism 600, and then placed at 25℃ for 12 hours for standby; the stirring time is 30 minutes; the stirring speed is 250r / min;

[0116] (S03) The mixed solution in step (S02) is added dropwise into the CaCl2 solution with a mass fraction of 1.27% through the liquid adding mechanism 1100 while stirring through the stirring mechanism 500, and then continuously stirred and mixed through the stirring mechanism 500 and the mixing mechanism 600 until solidification; the dropwise adding height is 10cm; the dropwise adding rate is 1.2ml / min; the stirring speed is 250r / min;

[0117] (S04) The material after curing in step (S03) is washed and dried by cleaning mechanism 800, and the IgY gel bead product is obtained. The drying method is vacuum drying, the vacuum pressure of vacuum drying is 600 MPa; the drying temperature of vacuum drying is 40℃; the drying time of vacuum drying is 24h.

[0118] Comparative Example 1:

[0119] An IgY gel bead includes the following components by weight parts,

[0120] Sodium alginate 1 part, IgY 0.25 parts, crosslinking agent 0.5 parts, and appropriate amount of water.

[0121] A preparation method of an IgY gel bead includes the following steps,

[0122] An appropriate amount of sodium alginate and IgY are added to a container containing distilled water through feeding mechanism 900, then heated by heating mechanism 1500 50℃ water bath, and then mixed and stirred by stirring mechanism 500 and mixing mechanism 600 until dissolved, and then placed at 25℃ for 12h for standby; the stirring time is 30min; the stirring speed is 250r / min;

[0123] The mixed solution is added to the CaCl2 solution with a mass fraction of 1.27% by adding liquid mechanism 1100 while stirring by stirring mechanism 500, and then continuously stirred and mixed by stirring mechanism 500 and mixing mechanism 600 until solidification; the drop height is 10cm; the drop rate is 1.2ml / min; the stirring speed is 250r / min;

[0124] The solidified material is washed and dried by cleaning mechanism 800, and the dried IgY-calcium alginate gel bead product is obtained. The drying method is vacuum drying, the vacuum pressure of vacuum drying is 600 MPa; the drying temperature of vacuum drying is 40℃; the drying time of vacuum drying is 24h.

[0125] Example 2:

[0126] Example 2 is basically the same as Example 1, except that: an IgY gel bead includes the following components by weight parts,

[0127] Sodium alginate 3.5 parts, modified shellac 10 parts, lecithin 1.5 parts, IgY 1.75 parts, crosslinking agent 3 parts, and appropriate amount of water.

[0128] Comparative Example 2:

[0129] Comparative Example 2 is basically the same as Comparative Example 1, except that: an IgY gel bead includes the following components by weight parts,

[0130] Sodium alginate 3.5 parts, IgY 1.75 parts, crosslinking agent 3 parts, and appropriate amount of water.

[0131] Example 3:

[0132] Example 3 is basically the same as Example 1, except that the IgY gel beads comprise, by weight parts, the following components:

[0133] Sodium alginate 1.5 parts, modified shellac 2 parts, lecithin 0.7 parts, IgY 0.5 parts, crosslinking agent 1 part, and appropriate amount of water.

[0134] Comparative Example 3:

[0135] Comparative Example 3 is basically the same as Comparative Example 1, except that the IgY gel beads comprise, by weight parts, the following components:

[0136] Sodium alginate 1.5 parts, IgY 0.5 parts, crosslinking agent 1 part, and appropriate amount of water.

[0137] Example 4:

[0138] Example 4 is basically the same as Example 1, except that the IgY gel beads comprise, by weight parts, the following components:

[0139] Sodium alginate 3 parts, modified shellac 8 parts, lecithin 1.2 parts, IgY 1.5 parts, crosslinking agent 2.5 parts, and appropriate amount of water.

[0140] Comparative Example 4:

[0141] Comparative Example 4 is basically the same as Comparative Example 1, except that the IgY gel beads comprise, by weight parts, the following components:

[0142] Sodium alginate 3 parts, IgY 1.5 parts, crosslinking agent 2.5 parts, and appropriate amount of water.

[0143] Example 5:

[0144] Example 5 is basically the same as Example 1, except that the IgY gel beads comprise, by weight parts, the following components:

[0145] Sodium alginate 2 parts, modified shellac 4 parts, lecithin 0.9 parts, IgY 0.7 parts, crosslinking agent 1.5 parts, and appropriate amount of water.

[0146] Comparative Example 5:

[0147] Comparative Example 5 is basically the same as Comparative Example 1, except that the IgY gel beads comprise, by weight parts, the following components:

[0148] Sodium alginate 2 parts, IgY 0.7 parts, crosslinking agent 1.5 parts, and appropriate amount of water.

[0149] Example 6:

[0150] Example 6 is substantially the same as Example 1, except that the IgY gel beads comprise, by weight parts, the following components:

[0151] 2.5 parts of sodium alginate, 6 parts of modified shellac, 1.1 parts of lecithin, 1.3 parts of IgY, 2 parts of crosslinking agent, and an appropriate amount of water.

[0152] Comparative Example 6:

[0153] Comparative Example 6 is substantially the same as Comparative Example 1, except that the IgY gel beads comprise, by weight parts, the following components:

[0154] 2.5 parts of sodium alginate, 1.3 parts of IgY, 2 parts of crosslinking agent, and an appropriate amount of water.

[0155] Example 7:

[0156] Example 7 is substantially the same as Example 1, except that the IgY gel beads comprise, by weight parts, the following components:

[0157] 2.2 parts of sodium alginate, 5 parts of modified shellac, 1 part of lecithin, 1 part of IgY, 1.8 parts of crosslinking agent, and an appropriate amount of water.

[0158] Comparative Example 7:

[0159] Comparative Example 7 is substantially the same as Comparative Example 1, except that the IgY gel beads comprise, by weight parts, the following components:

[0160] 2.2 parts of sodium alginate, 1 part of IgY, 1.8 parts of crosslinking agent, and an appropriate amount of water.

[0161] Experimental Example:

[0162] 1.1 Preparation of IgY-calcium alginate gel beads

[0163] An appropriate amount of sodium alginate was placed in a beaker containing distilled water and stirred to dissolve at a temperature of 50°C. After cooling, an appropriate amount of IgY was added and stirred at room temperature until completely dissolved and left to stand overnight to degas to obtain a capsule liquid. The capsule liquid containing IgY was dropped into a CaCl2 solution at 200-300 r / min using a sterile syringe, the dropping rate was maintained at 1 mL / min, the dropping height was about 5-10 cm from the liquid surface, and after dropping, the capsule liquid was left to stand for 30 min for solidification reaction with the CaCl2 solution. After crosslinking was completed, the gel beads were filtered and vacuum dried for 12 h to obtain dry IgY-calcium alginate gel beads.

[0164] 1.2 Determination of embedding rate and drug loading of gel beads

[0165] The CaCl2 cross-linking solution of different gel beads was collected respectively, and the content of free IgY in the cross-linking solution was determined by Coomassie brilliant blue method (Bradford). The specific steps were as follows: Coomassie brilliant blue reagent (5 mL) was added to 1 mL of IgY protein solution (1 mg / mL IgY) of different concentrations respectively, and the mixture was shaken uniformly and left to react for 5 min, then the absorbance value was measured at 595 nm. Taking the absorbance value as the vertical coordinate and the IgY protein concentration as the horizontal coordinate, the following linear regression equation was obtained: y = 4.522x + 0.0338, and the correlation coefficient R2 was 0.9902. An appropriate volume of sample to be tested (according to the protein content, the volume of the sample to be tested can be adjusted appropriately, so that the absorbance value is within the linear range of the standard curve) was added to 5 mL of Coomassie brilliant blue reagent, and the embedding rate and drug loading of the gel beads were calculated by formulas (1) and (2).

[0166] (1)

[0167] (2)

[0168] 1.3 Selection of different concentrations of sodium alginate

[0169] To study the effect of sodium alginate concentration on the performance of gel beads, the volume of each solution was kept constant, the concentration of CaCl2 was 1.5% (w / v), and the core-to-wall ratio was 3 / 6. Transparent and viscous sodium alginate solutions containing IgY were prepared at different concentrations of 1%, 1.5%, 2%, 2.5%, 3%, and 3.5% (w / v). The capsule solution was added dropwise into a 1.5% (w / v) CaCl2 solution at a rotation speed of 200-300 r / min, the distance between the liquid surface and the droplet was maintained at 5-10 cm, the drop rate was maintained at 1 mL / min, and then the gel beads were solidified for 30 min. After vacuum drying, IgY-calcium alginate gel beads with different concentrations of sodium alginate were obtained.

[0170] 1.4 Selection of different calcium chloride concentrations

[0171] To study the effect of CaCl2 concentration on the performance of microcapsules, the optimal conditions were kept unchanged on the basis of single factor, that is, the concentration of sodium alginate was 2.5% (w / v), the core-wall ratio was 3 / 6, and the capsule liquid was prepared. The capsule liquid was dropped into the CaCl2 solution with a speed of 200-300 r / min, and the concentration of CaCl2 solution was 0.5%, 1.0%, 1.5%, 2.5%, and 3% (w / v). The distance between the liquid surface and the dropping point was maintained at 5-10 cm, and the dropping speed was maintained at 1 mL / min. Then, the gel beads were solidified for 30 min, and IgY-calcium alginate gel beads with different CaCl2 concentrations were obtained after vacuum drying.

[0172] 1.5 Selection of different core-wall ratios

[0173] To study the effect of core-wall ratio on the performance of microcapsules, the optimal conditions were kept unchanged on the basis of single factor, that is, the concentration of sodium alginate was 2.5% (w / v), the concentration of CaCl2 was 1.5% (w / v), and the capsule liquid was prepared with different core-wall ratios (changing the proportion of core material while keeping the wall material unchanged): 1 / 6, 2 / 6, 3 / 6, 4 / 6, 5 / 6, and 6 / 6. The capsule liquid was dropped into the 1.5% (w / v) CaCl2 solution with a speed of 200-300 r / min. The distance between the liquid surface and the dropping point was maintained at 5-10 cm, and the dropping speed was maintained at 1 mL / min. Then, the gel beads were solidified for 30 min, and IgY-calcium alginate gel beads with different core-wall ratios were obtained after vacuum drying.

[0174] 2.1 Preparation of IgY-laccaic acid-egg phospholipid-calcium alginate gel beads

[0175] On the basis of using single wall material sodium alginate to prepare gel beads, a certain amount of modified laccaic acid, egg phospholipid, and sodium alginate were mixed to prepare IgY-laccaic acid-egg phospholipid-calcium alginate gel beads. The specific steps are as follows: an appropriate amount of laccaic acid was added to 0.1 mol / L Na2CO3 solution, stirred at 60°C until completely dissolved to obtain modified laccaic acid solution, and then an appropriate amount of sodium alginate was added, stirred and dissolved at 50°C. After cooling, an appropriate amount of egg phospholipid and IgY was added, stirred until completely dissolved at room temperature, and then deaerated overnight to obtain the capsule liquid. The capsule liquid containing IgY was dropped into the CaCl2 solution with a speed of 200-300 r / min, and the dropping speed was maintained at 1 mL / min. The dropping height was about 5-10 cm from the liquid surface. After dropping, the capsule liquid and CaCl2 solution were allowed to solidify for 30 min. After crosslinking, the gel beads were filtered and vacuum dried for 12 h. IgY-laccaic acid-egg phospholipid-calcium alginate gel beads were obtained after drying.

[0176] 3 Microstructure observation of the gel beads

[0177] The microstructure of the gel bead surface was observed by using a field emission scanning electron microscope (SEM). After vacuum drying, the sample was fixed on a sample stage, gold was sprayed, and the voltage was set to 15 kv. The observation was carried out at a magnification of 80 times and 1500 times.

[0178] 4 Determination of the swelling degree and in vitro release performance of the gel beads

[0179] According to the average digestion time of different foods in the human stomach, which is 1-2 h, and the residence time in the small intestine, which is 2-6 h, the release time of the gel beads in the simulated gastric juice is set to 2 h, and the release time in the intestinal juice is set to 2 h-4 h. Accurately weigh 10 mg of drug-loaded gel beads in a 25 mL conical flask, add 10 mL of simulated gastric juice (SGF), and shake in a constant temperature water bath shaker at 37°C and 100 r / min for 2 h. Every 1 h, filter the gel beads, absorb the water on the surface of the gel beads with filter paper, and then transfer them to 10 mL of simulated intestinal juice (SIF) for 2-4 h. Filter the gel beads at regular intervals, record the weight of the gel beads every 1 h in the simulated gastric and intestinal digestion juice, calculate the swelling degree, and draw the curve. At the same time, every 1 h, take the supernatant of the gastric and intestinal release liquid (supplemented with the same amount of liquid at the same temperature), filter it through a 0.22 μm filter membrane, and determine the content of IgY in the release liquid by the Coomassie brilliant blue method. Calculate the in vitro release rate of IgY and draw the curve. The calculation formulas of the swelling degree and the cumulative release rate of the gel beads are shown in (3) and (4):

[0180] (3)

[0181] In the formula: SR represents the swelling degree of the gel beads; Wa represents the mass of water in the gel beads, g (the mass of the swollen gel beads-the mass of the dry gel beads); Wb represents the mass of the dry gel beads before swelling, g.

[0182] ×100 (4)

[0183] In the formula: CR represents the in vitro cumulative release rate of the gel beads, %; Cn represents the IgY concentration measured at the nth sampling, mg / mL; V represents the total volume of the release liquid, mL; Cn-1 represents the IgY concentration measured at the (n-1)th sampling, mg / mL; Vn-1 represents the volume of the (n-1)th sampling, mL; Wb represents the mass of the dry gel beads before swelling, g; LE is the drug loading capacity of the gel beads, %.

[0184] Preparation of simulated gastric juice: accurately weigh NaCl 0.1755 g, pepsin 1 g, and concentrated hydrochloric acid 7 mL, adjust the pH value to 1.2 with concentrated hydrochloric acid, and make up to 100 mL with distilled water.

[0185] Preparation of simulated intestinal fluid: accurately weigh KH2PO40.68 g, trypsin 1 g, adjust the pH value to 6.8 with 1 mol / L NaOH solution, and dilute with distilled water to 100 mL.

[0186] 4.1 Preparation of E. coli antigen

[0187] Take the E. coli bacterial solution from the 4°C refrigerator, and inoculate 100 μL of the bacterial solution into sterilized LB broth liquid medium (2.5 g of LB broth powder dissolved in 100 mL of distilled water) in an anaerobic state at 37°C for 24 h. Pour the bacterial solution into a sterilized 10 mL centrifuge tube and centrifuge at 4000 r / min for 15 min. Pour off the supernatant and inoculate the remaining bacterial solution into a newly prepared 100 mL LB broth liquid medium in an anaerobic state for another 24 h of expansion culture. Dilute 100 μL of the bacterial solution from the expanded culture at concentrations of 10-1, 10-2, 10-3, 10-4, 10-5, 10-6, and 10-7 with 0.03 mol / L PBS solution. Then, take 100 μL of the bacterial solution from different dilution concentrations and place it in a sterile blank petri dish. Pour 1.5% agar powder into the petri dish, cover it with a lid, and shake it clockwise. Then, place it in an incubator (37°C, anaerobic) for 48 h of culture. Count the number of E. coli at different dilution concentrations using the plate count method to find the most suitable dilution concentration, which maintains the bacterial concentration at 1.7 x 109 CFU / mL (consistent order of magnitude).

[0188] Break the obtained bacterial solution as follows: divide the bacterial solution diluted at the most suitable dilution concentration into 5 different sterile sampling bags, and add 0.3 mL of phenol to each 100 mL of the bacterial solution. Break the bacterial solution using an ultrasonic cell crusher under ice bath conditions for 3 s, stop for 3 s, continue breaking for 10 min, and stop for 5 min. Repeat the breaking process once more under the same conditions to obtain an antigen solution with a breaking rate of 50-60%. Divide the solution into 10 mL centrifuge tubes and store them at -20°C.

[0189] 4.2 Activity determination of immunoglobulin (IgY)

[0190] The activity of IgY was determined by indirect ELISA method, and the specific steps were as follows: according to the number of samples to be determined, sample groups and blank groups were designed in 96-well enzyme-labeled plates, 120 μL of broken antigen solution was added to each well, and after overnight incubation at 4°C, it was taken out and placed on a sterile operation table, the liquid in each well was discarded and 300 μL of 1% standard bovine serum protein solution was added for blocking, and it was placed in an incubator for incubation at 37°C for 2 h; the bovine serum protein solution in each well was discarded, 100 mL of IgY sample solution diluted according to the gradient (IgY concentration was 1 mg / mL, 0.5 mg / mL, 0.25 mg / mL, 0.125 mg / mL, 0.0625 mg / mL) was added, and it was incubated at 37°C for 2 h; the sample solution in each well was discarded, 120 μL of rabbit anti-chicken IgG-HRP (dilution of conjugate 1:5000) was added to each well, and it was incubated at 37°C for 1 h, then the liquid in the well was discarded, 250 μL of PBST solution (PBS-0.05% Tween, adjusted to pH 7.4 with 0.5 mol / L NaOH) was used for washing, and the washing was repeated 5 times with an interval of 60 s; then 100 μL of TMB single-component color developing solution was added to each well for color development, and it was incubated in a 37°C incubator for 15 min; after the reaction was completed, 50 μL of 10% sulfuric acid was added to each well to terminate the reaction, and the absorbance value was determined at an absorbance of 450 nm by using an enzyme-labeled instrument.

[0191] 4.3 Determination of activity retention rate of immunoglobulin (IgY)

[0192] The dried gel beads were placed in the mixed disintegration solution (0.2 mol / L NaHCO3 solution and 0.06 mol / L Na3C6H5O7·2H2O solution with pH of 8.0), stirred for 3 h until the gel beads were completely dissolved, centrifuged at 4000 r / min for 15 min, and the supernatant was taken, the activity of IgY in different wall material gel beads was determined, the total content of IgY in the supernatant after centrifugation was determined by using Coomassie brilliant blue method (Bradford), and the activity of untreated IgY at the same concentration was obtained by converting the four-parameter Logistic standard curve obtained by fitting the IgY activity values at different dilution concentrations, and the four-parameter Logistic curve fitting equation was as shown in formula (5):

[0193] (5)

[0194] In the formula, x represents the concentration of IgY, mg / mL; y represents OD 450nm ; A1=2.81427, A2=-0.30957, X0=4.78922, P=0.921, R 2 =0.99687.

[0195] The activity retention rate of IgY was calculated according to formula (6):

[0196] x 100 (6)

[0197] 4.4 Structural analysis of immunoglobulin (IgY)

[0198] The structure of IgY in the in vitro release solution of microcapsules was analyzed by SDS-PAGE gel electrophoresis. The separation gel concentration was 10%, and the concentrated gel concentration was 4%. The preparation method of SDS-polyacrylamide gel is shown in Table 1.

[0199] Table 1: Composition of SDS-polyacrylamide gel

[0200] Reagents Required 10% Resolving Gel 4% Concentration Gel A Solution 3.33 mL 0.67 mL B Solution 2.5 mL --- Distilled Water 4.16 mL 2.4 mL 10% SDS --- 50 μL 1 M Tris-Hcl --- 1.875 mL 10% Ammonium Persulfate 50 μL 25 μL TEMED 5 μL 5 μL Total Volume 10 mL 5 mL

[0201] Wherein, preparation of A liquid: accurately take acrylamide 29.2 g, bisacrylamide 0.8 g, add distilled water to 100 mL, stir with glass rod until completely dissolved, prepare 100 mL acrylamide storage solution; preparation of B liquid: mix 4x separation gel buffer 100 mL, 2M Tris-Hcl (pH 8.8) 75 mL, 10% SDS 4 mL and distilled water 21 mL to prepare 200 mL of B liquid; preparation of 1L electrode buffer: accurately weigh Tris 3 g, glycine 14.4 g, SDS 1 g, add water, stir and dissolve, and dilute to 1L, adjust pH to 8.3; preparation of sample loading buffer: mix 1M Tris-Hcl (pH 6.8) 0.6 mL, 50% glycerol 5 mL, 10% SDS (electrophoresis grade) 2 mL, 0.1% (w:v) bromophenol blue and distilled water 0.9 mL.

[0202] 5 Results and analysis

[0203] 5.1 Effect of sodium alginate concentration on gel bead preparation process

[0204] In the process of preparing microcapsules, embedding rate and drug loading are usually used as two important indicators to evaluate the embedding efficiency of the embedding system. Embedding rate represents the proportion of drugs embedded in gel bead particles. Increasing the embedding rate can improve the utilization rate of drugs and reduce the waste of drugs in the embedding process. Drug loading represents the amount of drugs loaded per unit mass of gel bead particles, which is related to the content of embedded drugs and the mass of drug particles. Drug loading is the drug content per unit mass of gel bead particles, which is related to the content of embedded drugs and the mass of drug particles. Taking embedding rate and drug loading as the main indicators, IgY gel beads were prepared by using different concentrations of sodium alginate, and the effect of sodium alginate concentration on gel bead preparation process was as follows Figure 13As shown, with the continuous increase of sodium alginate concentration, the encapsulation efficiency showed a trend of gradually increasing and then decreasing, and the trend of drug loading was the same as that of encapsulation efficiency. When the sodium alginate concentration was 1% (w / v), the encapsulation efficiency was 3.67%. Due to the low sodium alginate concentration, less sodium alginate and Ca2+ were used. 2+ The reaction occurs, and the outer membrane of the formed gel beads is too thin and difficult to shape, leading to enhanced permeability of the gel beads and easy loss of IgY, resulting in a low encapsulation efficiency. As the sodium alginate concentration gradually increases, the encapsulation efficiency and drug loading also gradually increase. This is because more sodium alginate reacts with Ca... 2+ The reaction occurs, forming a more tightly connected network-like outer membrane of the gel beads, reducing the surface pore size and preventing IgY diffusion and loss from the inside to the outside of the gel beads. When the sodium alginate concentration is 3% (w / v), the encapsulation efficiency of the gel beads reaches its maximum of 53.54%, and the drug loading reaches 17.85%. When the sodium alginate concentration exceeds 3% (w / v), the encapsulation efficiency and drug loading decrease rapidly to 28.25% and 9.42%, respectively. Although the encapsulation efficiency is best at a sodium alginate concentration of 3% (w / v), excessively high concentrations can cause the extruded gel beads to easily clump together, resulting in incomplete and uneven particles. Therefore, the optimal sodium alginate concentration for preparing the gel beads is chosen to be 2.5% (w / v), at which point the encapsulation efficiency is 50.9% and the drug loading is 16.97%.

[0205] 5.2 Effect of CaCl2 concentration on the preparation process of gel beads

[0206] The effect of CaCl2 concentration on the gel bead preparation process, such as Figure 14 As shown, with the continuous increase of CaCl2 concentration, the encapsulation efficiency and drug loading of the gel beads exhibit the same trend: a slow increase followed by a rapid peak and then a rapid decrease. When the CaCl2 concentration is 0.5% (w / v), the encapsulation efficiency and drug loading are 25.93% and 8.64%, respectively. With the gradual increase of CaCl2 concentration, the encapsulation efficiency and drug loading show a slight increase. When the CaCl2 concentration is 1.5% (w / v), the encapsulation efficiency and drug loading reach their maximum values ​​of 40.64% and 13.55%, respectively. When the CaCl2 concentration exceeds 1.5% (w / v), both the encapsulation efficiency and drug loading decrease rapidly. At a CaCl2 concentration of 2% (w / v), the encapsulation efficiency and drug loading are 22.39% and 7.46%, respectively; at a CaCl2 concentration of 2.5% (w / v), the encapsulation efficiency and drug loading are 22.63% and 7.54%, respectively. This phenomenon may be due to the presence of Ca in the low-concentration CaCl2 solution. 2+ It reacts with sodium alginate to form a relatively sparse network structure, through which Ca... 2+will further extend inward and cross-link with sodium alginate to form a thicker and sparse film, which is easy to cause the core material to diffuse and lose in the water phase, resulting in low embedding rate and drug loading; when the concentration of CaCl2 continuously increases, more Ca 2+ will cross-link with sodium alginate, at which time the embedding rate and drug loading can reach the maximum value; but when the concentration of CaCl2 is too high, more Ca 2+ will quickly form a layer of tight and thick film with sodium alginate, and due to the decrease of the permeation effect caused by the decrease of the pore size on the surface of the gel beads, the diffusion of Ca 2+ in the CaCl2 solution into the interior of the gel beads is reduced, resulting in the decrease of the embedding rate and drug loading of the gel beads.

[0207] 5.3 Effect of core-wall ratio on the preparation process of gel beads

[0208] As shown in Figure 15 , under the condition that the core material increases and the wall material remains unchanged, the embedding rate shows a trend of first increasing and then decreasing, while the drug loading shows a continuous increase. When the core-wall ratio increases from 1 / 6 to 2 / 6, the embedding rate of the gel beads increases from 19.58% to 21.26%, and the drug loading increases from 2.8% to 5.32%. When the core-wall ratio is 3 / 6, the embedding rate and drug loading of the gel beads are the highest, which are 31.44% and 10.48%, respectively. With the further increase of the ratio of core material to wall material, the embedding rate of the gel beads decreases to 28.17%, 27.92%, and 26.65%, while the drug loading increases with the increase of the core-wall ratio, and when the core-wall ratio is 6 / 6, the drug loading reaches the maximum value of 13.32%. This may be because as the mass ratio of IgY to sodium alginate increases, the proportion of IgY in the capsule-forming solution increases, and therefore the drug loading also increases. However, due to the increase of the content of IgY in the core material, too much IgY cannot be integrated with sodium alginate, which leads to the loss of the core material and unnecessary waste. Therefore, it is appropriate to choose the core-wall ratio of 3 / 6.

[0209] 5.4 Swelling degree diagram of IgY-calcium alginate gel beads

[0210] After the calcium alginate gel beads are incubated in gastric juice (SGF) for 2 h, the swelling degree is about 0.89. When the gel beads are transferred to intestinal juice (SIF) for 1 h, the swelling degree reaches 2.26, which is increased by 2.4 times. The gel bead particles rapidly absorb water and swell, and after 2 h in the simulated intestinal juice, the swelling degree is more than 5.8 times. With the extension of time, the gel bead particles continue to absorb water, which continuously increases the swelling degree, but when the swelling degree increases to a certain extent, the gel bead particles will be dissolved in the intestinal juice.

[0211] As shown in Figure 16The swelling graph of the gel beads with different sodium alginate concentrations is shown. The swelling degree of the gel beads with 1.0% (w / v) and 1.5% (w / v) sodium alginate concentrations in SIF for 1h-2h is higher than that of the other four groups. It may be due to the low concentration of sodium alginate, the mechanical strength of the prepared gel beads is too low to increase the swelling rate in SIF, while with the increase of sodium alginate concentration, more sodium alginate molecules react with Ca2+ to make the particles more dense and the mechanical strength improved, thus leading to the decrease of solvent permeation rate, and the swelling degree is lower than that of the group with 1.0% (w / v) and 1.5% (w / v) sodium alginate concentrations.

[0212] As shown in Figure 17 The swelling graph of the gel beads with different CaCl2 concentrations is shown. CaCl2 concentration can affect the gel morphology of the gel bead surface. After the gel beads with different CaCl2 concentrations swell in SIF for 2h, the swelling degree changes in the order of 3.0% (w / v) > 1.5% (w / v) > 2.5% (w / v) > 1.0% (w / v) > 0.5% (w / v). The swelling degree of the gel beads with low CaCl2 concentration is higher than that of the gel beads with high CaCl2 concentration, which may be because the Ca 2+ The thick film formed immediately after reaction with sodium alginate makes the initial swelling rate low in swelling; but when the gel beads swell, the surface pore size becomes larger, and the solvent quickly penetrates through the thin gel layer, making the swelling degree increase rapidly.

[0213] As shown in Figure 18 The swelling degree graph of the gel beads with different core-to-wall ratios is shown. When the gel beads are transferred to SIF for 1h, the higher the IgY addition amount, the higher the swelling degree; and when the swelling continues in SIF for 2h, the swelling degree changes in the order of 6 / 6 > 4 / 6 > 3 / 6 > 2 / 6 > 1 / 6 > 5 / 6. This may be because the excessive IgY on the surface of the gel beads has been dissolved, and the IgY content and distribution in the gel beads with different IgY addition amounts are different, resulting in different dissolution rates, which affect the swelling rate and final swelling degree of the gel beads.

[0214] 5.5 In vitro release rate of IgY-calcium alginate gel beads

[0215] The swelling degree of the gel beads in the gastrointestinal model affects the release degree of the core material. After the gel beads swell, the pore size on the surface also increases, so the core material of the gel beads is also released. As shown in Figure 19As shown, after gel beads with different sodium alginate concentrations swelled in SGF for 2 hours, the IgY release rate ranged from 10% to 20%. This may be because some IgY was present on the surface of the gel beads during preparation, so it dissolved upon entering the SGF. Furthermore, the gel beads made from sodium alginate as a single wall material have relatively large pore sizes, making the core material easier to dissolve. However, after transferring the gel beads to SIF for 1 hour, the gel beads rapidly absorbed water and swelled, increasing their swelling rate and surface pore size, resulting in rapid IgY release. The cumulative release rate reached over 80%, and IgY continued to be released, with almost all of it released after 2 hours in SIF. This indicates that the release rate of gel beads with different sodium alginate concentrations in the stomach did not change significantly. However, after transferring the gel beads to SIF, the release rate slowed down with increasing sodium alginate concentration. This may be because high concentrations of sodium alginate made the gel beads more compact, resulting in lower swelling and a slower release rate.

[0216] like Figure 20 As shown, the concentration of CaCl2 solution affects the release rate of gel beads. When the gel beads are in SGF, the release rate of gel beads with a CaCl2 concentration of 2% (w / v) in gastric fluid is higher than that of other groups. However, after being transferred to SIF, the release rate slows down. As the concentration of CaCl2 increases, the final release rate of gel beads also decreases. This may be because the outer membrane of gel beads prepared with high concentration CaCl2 solution is thinner, which slows down the release rate. Conversely, the release rate of gel beads prepared with low concentration CaCl2 solution is faster in intestinal fluid.

[0217] like Figure 21 The core-to-wall ratio shown affects the content and distribution of IgY in the gel beads, further influencing release characteristics. The release rate of gel beads with different core-to-wall ratios in SGF showed no regular variation. However, after transfer to SIF, gel beads with a core-to-wall ratio of 6 / 6 exhibited the fastest release rate, possibly due to their increased IgY content leading to higher drug loading. Furthermore, compared to other groups, they had higher IgY content both on their surface and inside, resulting in a faster release rate. The release rates of gel beads with core-to-wall ratios of 4 / 6 and 3 / 6 also increased with increasing IgY addition, presumably because the IgY content on their surface increased with increasing IgY addition, leading to higher dissolution rates.

[0218] 5.6 Effect of Shellac Concentration on IgY Gel Bead Encapsulation Efficiency

[0219] IgY-shellac-lecithin-calcium alginate gel beads were prepared by adding modified shellac and lecithin at different concentrations to the optimal preparation process conditions using sodium alginate as the main wall material. Figure 22It can be seen that as the shellac concentration increases, the encapsulation efficiency gradually decreases after increasing, and the trend of drug loading is the same as that of encapsulation efficiency. When the shellac concentration is 0.5% (w / v), the encapsulation efficiency is 74.9%, and the drug loading is 25.95%. As the shellac concentration increases, both the encapsulation efficiency and drug loading also increase. This may be because the addition of shellac fills the gaps between sodium alginate and calcium. 2+ The voids formed during the reaction make the outer membrane of the network-structured gel beads more tightly connected, reducing the surface pore size and preventing the diffusion and loss of IgY from the inside to the outside of the gel beads. When the shellac concentration is 1.5% (w / v), the encapsulation rate of the gel beads reaches its maximum of 85.49%, and the drug loading reaches 29.62%. This is likely because the increased shellac concentration makes the gel beads more dense, reducing IgY exudation, which is beneficial for core material encapsulation. When the shellac concentration is 2.5% (w / v), the encapsulation rate and drug loading show a decreasing trend, with the encapsulation rate decreasing to 83.83% and 29.04%, respectively. When the shellac concentration is 10%, the encapsulation rate and drug loading of the gel beads decrease to 78.54% and 27.21%, respectively. At this point, the mechanical strength of the gel beads is weak, and they break easily. Furthermore, the increased shellac concentration makes the gel beads more dense, reducing IgY exudation, which is beneficial for core material encapsulation. Therefore, the optimal shellac concentration for preparing gel beads is 1.5% (w / v).

[0220] 5.7 Comparison of the ultrastructure of single-wall material gel beads and composite wall material gel beads

[0221] Depend on Figure 23 It can be seen that gel beads prepared using sodium alginate show up under low magnification (...). Figure 23 Under -a) the gel beads are round and smooth, but under high magnification (... Figure 23 Under -b) it can be seen that the surface of the gel beads has many cracks and the gaps are relatively large; the gel beads prepared using sodium alginate and shellac-lecithin as composite wall materials are examined under low magnification ( Figure 23 Under -c) the gel beads are round, but the surface is not smooth. Under high magnification ( Figure 23 -d) The surface of the gel beads has small wavy grooves and a compact structure. Based on the above results, it can be seen that the IgY gel beads prepared by combining sodium alginate and shellac-lecithin have a more compact structure under high magnification than gel beads prepared by a single wall material, thus better preserving the activity of IgY and reducing loss.

[0222] 5.8 Effect of composite wall materials on the activity of IgY gel beads

[0223] When the concentration of sodium alginate was 2.5% (w / v), the activity retention rate of IgY gel beads was only 52%; when the concentration of sodium alginate was 2.5% (w / v), the concentration of modified shellac was 1.5% (w / v), and the concentration of lecithin was 1% (w / v), the activity retention rate of IgY gel beads was 92%, which was 40% higher than that of IgY gel beads prepared by using single wall material sodium alginate. This shows that the use of modified shellac-lecithin wall material can effectively improve the embedding rate and drug loading of IgY gel beads, which can avoid the loss of excessive activity.

[0224] 5.9 Swelling degree of IgY-shellac-lecithin calcium alginate gel beads

[0225] As Figure 24 The swelling degree of gel beads with different shellac concentrations is shown in the figure. The swelling degree of gel bead particles increased when they were transferred from SGF to SIF for 1 h, but the swelling degree of gel bead particles with a shellac concentration of 10% (w / v) increased instead after 1 h to 2 h in SIF. This may be because the high concentration of shellac led to strong toughness and thick outer membrane of the gel bead particles, which caused the swelling degree to continue to rise. The other four groups showed a downward trend compared with this group, indicating that after 2 h of digestion in intestinal juice, the gel bead particles with lower shellac concentration gradually melted and released the core material, causing the swelling degree to decrease and the release rate to increase.

[0226] 5.10 In vitro release rate of IgY-shellac-lecithin calcium alginate gel beads

[0227] As Figure 25 shown, after 2 h of swelling in SGF, the release rate of IgY was between 9% and 16% for gel beads with different shellac concentrations. After 1 h of transfer to SIF, gel beads with a shellac concentration of 0.5% to 5% (w / v) rapidly absorbed water and swelled, increasing their swelling rate and surface pore size, which caused IgY to be rapidly released, with a cumulative release rate of more than 80% and continuous release. After 2 h in SIF, the release rate of IgY was more than 90%. However, the release rate of gel beads with a shellac concentration of 10% (w / v) was about 83% after 2 h in SIF, which was relatively slow compared with the other groups. This shows that the shellac concentration has a significant impact on the release rate of gel beads. The surface structure of gel beads prepared by shellac-lecithin and sodium alginate is relatively tight, which reduces the swelling degree and slows down the release rate. Therefore, the release rate of gel beads prepared by single wall material sodium alginate is significantly lower in the stomach, and the release is basically complete after 2 h of incubation in the intestine.

[0228] 6 Conclusion

[0229] IgY is an immunoglobulin with high activity, which is closely related to human health. In order to reduce the loss of IgY activity in the process of use, the microcapsule technology is used to prepare the IgY as the core material into millimeter level hydrogel beads. Because the core material is isolated from the outside world, it can be released only under appropriate pH conditions, so that the microcapsule technology can protect the active substances, reduce the reaction of external adverse factors (such as light, heat, oxygen, etc.) with the core material and control the release of the core material; at the same time, it can also prolong the shelf life of the product and reduce the loss of IgY activity. In the application, sodium alginate is used as the main wall material, and shellac and lecithin are used as the composite wall material. The IgY is prepared into gel beads by sharp hole-coagulation bath method, so as to reduce the loss of activity in the stomach and make it reach the intestine to play the effect.

[0230] 6.1 Preparation process and physical properties of single-wall IgY gel beads

[0231] (1) The optimal preparation process conditions of sodium alginate-embedded IgY gel beads are as follows: the concentration of sodium alginate is 2.5% (w / v), the concentration of CaCl2 is 1.5% (w / v), and the core-wall ratio is 0.53:1. Under the optimal conditions, the embedding rate of the prepared gel beads is 43.3%, and the drug loading capacity is 14.98%. The order of the influence of each factor on the preparation process of the gel beads is as follows: the concentration of sodium alginate > the core-wall ratio > the concentration of CaCl2, and the preparation conditions have no effect on the activity of IgY.

[0232] (2) The freshly prepared IgY-calcium alginate gel bead particles have good roundness and uniformity. The wet gel bead particle size is concentrated in the range of 2-2.4 mm, the average hardness before drying is 150.8 g, the average hardness of the gel beads after drying by different drying methods is greater than 2000 g, the swelling degree of the gel beads in the simulated gastric juice after 2 h is about 0.89, and the cumulative release rate of IgY is about 20%-30%. However, when the gel beads are transferred to the simulated intestinal juice for 1 h, the swelling degree reaches 2.26, which is increased by 2.4 times, and the cumulative release rate of IgY is about 60%. After 2 h in the simulated intestinal juice, the swelling degree is more than 5.8 times, and IgY is basically released.

[0233] 6.2 Preparation process and physical properties of composite-wall IgY gel beads

[0234] (1) When the modified shellac with a concentration of 1.5% (w / v), 1% (w / v) lecithin and sodium alginate are compounded to prepare IgY-calcium alginate-shellac- lecithin gel beads, the embedding effect is the best, the embedding rate is 85.49%, the drug loading is 29.62%. The wet gel bead size is concentrated between 2-2.4 mm, the average hardness of the gel bead after vacuum drying is greater than 2000 g, the swelling degree of the gel bead is 0.5 after 2 h in the simulated gastric juice, the cumulative release rate of IgY is about 20%-30%, but when the gel bead is transferred to the simulated intestinal juice for 1 h, the swelling degree reaches 4.01, which is 8 times higher, the cumulative release rate of IgY is about 60%, after 2 h in the simulated intestinal juice, the swelling degree decreases to about 3.11, which indicates that the cumulative release rate of IgY is more than about 80%. In the electrophoresis result, no protein band is detected after the unembedded IgY is incubated in the gastric juice for 2 h, but the protein band is detected after 1 h and 6 h in the intestinal juice, and the IgY embedded by different wall materials can be detected after 2 h in the gastric juice and 6 h in the intestinal juice, which indicates that the embedding of IgY can resist the digestion of pepsin and acidic gastric juice, so as to realize the targeted release in the intestinal juice.

[0235] (2) The activity of IgY embedded by different wall materials is in the order of IgY-calcium alginate-shellac-lecithin gel bead > IgY-calcium alginate gel bead, and the activity is 92%, 52% respectively.

[0236] Finally, it should be pointed out that: the above embodiments are only used to illustrate the technical solutions of the present application, but not to limit them; although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that: it can still modify the technical solutions recorded in the foregoing embodiments, or make equivalent replacement for part or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A method for the preparation of IgY gel beads, characterized by: Comprising the following steps, (S01) Take the appropriate amount of shellac powder by feeding mechanism (900) into the Na2CO3 solution, then heated by heating mechanism (1500) water bath, and then mixed and stirred by stirring mechanism (500) and mixing mechanism (600) to obtain modified shellac solution; (S02) Take the appropriate amount of sodium alginate, lecithin and IgY by feeding mechanism (900) and mix with the modified shellac solution in step (S01), then heated by heating mechanism (1500) water bath, and then mixed and stirred by stirring mechanism (500) and mixing mechanism (600) until dissolved, and then stand by; (S03) The mixed solution in step (S02) is added by liquid adding mechanism (1100) and stirred by stirring mechanism (500) until the CaCl2 solution is added, and then continuously stirred and mixed by stirring mechanism (500) and mixing mechanism (600) until solidification; (S04) The solidified material in step (S03) is washed and dried by cleaning mechanism (800) to obtain IgY gel bead finished product; The preparation equipment of IgY gel bead comprises a base (100), a supporting plate (200) is fixedly installed on one side of the top of the base (100), a fixed plate (300) is arranged above the supporting plate (200), a preparation box (400) is arranged below the fixed plate (300) and on one side of the supporting plate (200), a heating mechanism (1500) is arranged in the preparation box (400), a stirring mechanism (500) is arranged in the heating mechanism (1500), a cleaning mechanism (800) is arranged in the heating mechanism (1500) and on one side of the stirring mechanism (500), a feeding mechanism (900) is arranged above the heating mechanism (1500) and on one side of the stirring mechanism (500), a liquid adding mechanism (1100) is fixedly arranged on the side, away from the supporting plate (200), of the preparation box (400), a mixing mechanism (600) is arranged on the side, close to the supporting plate (200), of the preparation box (400), and a driving mechanism (700) is arranged below the mixing mechanism (600). ​ The liquid adding mechanism (1100) comprises a liquid adding cylinder (1101) and an adjusting assembly (1200), the preparation box (400) is fixedly connected with the liquid adding cylinder (1101) away from one side of the support plate (200), the inside of the liquid adding cylinder (1101) is slidably connected with a piston (1102), the top of the piston (1102) is fixedly connected with a second push rod (1103), one end of the second push rod (1103) extends to the outside of the liquid adding cylinder (1101), one end of the second push rod is fixedly connected with a mounting plate (1104), the top of the mounting plate (1104) is provided with the adjusting assembly (1200), one end of the fixed plate (300) close to the motor (501) is fixedly connected with a connecting strip (1105), the bottom of the connecting strip (1105) is fixedly connected with a third push rod (1106), the outside of the second push rod (1103) between the piston (1102) and the liquid adding cylinder (1101) is sleeved with a second spring (1110), one side of the second spring (1110) away from the preparation box (400) is fixedly connected with a liquid inlet pipe (1108), the inside of the liquid inlet pipe (1108) is fixedly connected with a first electromagnetic valve (1109), the top of the liquid inlet pipe (1108) is fixedly connected with a liquid storage cylinder (1107), the outside of the liquid inlet pipe (1108) is fixedly connected with a reinforcing rod (1112), one end of the reinforcing rod (1112) is fixedly connected with the outside of the liquid adding cylinder (1101), the top of the liquid adding cylinder (1101) is symmetrically provided with air holes (1111) on both sides, and the bottom of the liquid adding cylinder (1101) is fixedly connected with a liquid delivery pipe. The IgY gel beads comprise the following components by weight parts, Sodium alginate 1-3.5 parts, modified shellac 0.5-10 parts, lecithin 0.5-1.5 parts, IgY 0.25-1.75 parts, crosslinking agent 0.5-3 parts, and appropriate amount of water.

2. The method of claim 1, wherein the IgY gel beads are prepared by the following steps: The IgY gel beads comprise the following components by weight parts, Sodium alginate 1.5-3 parts, modified shellac 2-8 parts, lecithin 0.7-1.2 parts, IgY 0.5-1.5 parts, crosslinking agent 1-2.5 parts, and appropriate amount of water.

3. The method for preparing IgY gel beads according to claim 1, characterized in that: In step (S01), the water bath temperature is 55-65 DEG C, and the stirring time is 20-40 min; in step (S02), the water bath temperature is 35-45 DEG C, the stirring time is 20-40 min, the standing temperature is 22-28 DEG C, the standing time is 8-24 h, the stirring speed is 200-300 r / min, and the crosslinking agent is anhydrous calcium chloride solution.

4. The method of claim 1, wherein the Na 2CO3 solution concentration is 0.1 mol / l; CaCl2 solution mass concentration is 1.27%; drop height is 10 cm; drop rate is 1ml / min~1.5ml / min; drying is vacuum drying; vacuum drying vacuum pressure is 500MPa~700MPa; vacuum drying drying temperature is 35℃~45℃; vacuum drying drying time is 20h~28h.

5. The method for preparing IgY gel beads according to claim 1, characterized in that: The stirring mechanism (500) includes a motor (501) fixedly installed on the top of the fixed plate (300), the output end of the motor (501) extends to the inside of the preparation box (400) through the fixed plate (300), the output end of the motor (501) is fixedly connected with a rotating plate (503), the bottom of the rotating plate (503) is fixedly connected with a rotating rod (502), the outer side of the rotating rod (502) is slidably connected with a sliding rod (507), the outer wall of the rotating rod (502) is fixedly connected with a first sliding block (509) on both sides in a symmetrical manner, the inner wall of the sliding rod (507) is provided with a first sliding groove (508) matched with the first sliding block (509) on both sides in a symmetrical manner, and the first sliding block (509) and the first sliding groove (508) are slidably connected, the top of the sliding rod (507) is fixedly connected with an inclined plate (505), a first spring (504) is sleeved on the outer side of the rotating rod (502) between the inclined plate (505) and the rotating plate (503), the inclined plate (505) is slidably connected with the outer side of the rotating rod (502), the outer wall of the sliding rod (507) is fixedly connected with a first stirring rod (510) on both sides in a symmetrical manner, the same side two first stirring rods (510) are fixedly connected with a second stirring rod (511), and the top of the motor (501) and one side of the rotating plate (503) are fixedly connected with a first push rod (506).

6. The method of claim 5, wherein the IgY gel beads are prepared by the following steps: The mixing mechanism (600) includes a first gear (601), a first rotating shaft (603) is rotatably connected to the bottom of the fixed plate (300) and one side away from the motor (501), a second gear (602) is fixedly connected to the outer side of the first rotating shaft (603), the first gear (601) is fixedly connected to the outer side of the output end of the motor (501), the first gear (601) is in meshing connection with the second gear (602), a third gear (604) is fixedly connected to the outer side of the first rotating shaft (603) and below the second gear (602), a gear ring (605) is fixedly installed on the outer wall of the preparation box (400), the third gear (604) is in meshing connection with the gear ring (605), a reinforcing seat (2000) is fixedly connected to one side of the support plate (200) close to the preparation box (400), and the first rotating shaft (603) is rotatably connected with the inside of the reinforcing seat (2000).

7. The method for preparing IgY gel beads according to claim 6, characterized in that: The cleaning mechanism (800) comprises a main water pipe (801), the bottom of which is rotationally connected in the preparation box (400), both sides of the inside of the main water pipe (801) are fixedly connected with branch water pipes (802), one end of each of the two branch water pipes (802) is fixedly connected with a connecting pipe (803), the inside of each of the two connecting pipes (803) is fixedly connected with a spray head (804) at equal intervals, the bottom end of the main water pipe (801) extends to the inside of the base (100), the bottom end of the main water pipe (801) is connected with a rotary joint (805), the rotary joint (805) is connected with a water inlet pipe (806) away from the supporting plate (200), and the outside of the main water pipe (801) and below the branch water pipes (802) are provided with a scraping assembly (1300).

8. The method for preparing IgY gel beads according to claim 7, characterized in that: The driving mechanism (700) comprises a first connecting seat (701), the bottom end of the first connecting seat (701) is fixedly connected with a first rotating shaft (603), the bottom of the first connecting seat (701) is rotationally connected with the top of the base (100), the outside of the first connecting seat (701) is rotationally connected with a connecting ring (702), one side of the connecting ring (702) away from the supporting plate (200) is fixedly connected with a connecting rod (703), one end of the connecting rod (703) is rotationally connected with a second connecting seat (704), one end of the second connecting seat (704) is fixedly connected with a first gear rack (705), the outside of the main water pipe (801) and between the base (100) and the preparation box (400) is fixedly connected with a fourth gear (706), the fourth gear (706) is in meshing connection with the first gear rack (705), and the bottom of the first gear rack (705) is provided with a limiting assembly (1700).

Images