Traditional Chinese medicine active component polymer nano-carrier synthesis reaction kettle

Abstract

The invention belongs to the technical field of reaction kettles, and discloses a traditional Chinese medicine active component polymer nano-carrier synthesis reaction kettle which comprises a tank body provided with a gas conveying assembly and a material conveying assembly, and an intelligent constant-temperature heating assembly is arranged on the side wall of the tank body; the hollow backflow type stirring assembly is arranged in the tank body, the stirring assembly comprises a stirring rod and a plurality of hollow backflow type stirring paddles fixed on the outer wall surface of the stirring rod, a plurality of spraying holes are formed in the side walls of the hollow backflow type stirring paddles, the spraying holes are communicated with the outside of the tank body through the stirring rod, and the spraying holes are used for spraying water or air; the blocking piece is movably arranged in the hollow backflow type stirring paddle, when the interior of the stirring rod is not ventilated or water is introduced, the blocking piece is used for blocking the plurality of spraying holes, and when the interior of the stirring rod is ventilated or water is introduced, the stirring rod is communicated with the plurality of spraying holes; the driving part is fixed at the top end of the tank body and is in transmission connection with the stirring rod. The method has important application value for designing and realizing an automatic system for the production process of the traditional Chinese medicine active component polymer imprinted nanoparticles.

Description

Technical Field

[0001] The invention relates to the technical field of reactors, in particular to a synthesis reactor for self-assembly of high molecular nano-carriers of traditional Chinese medicine active molecules. Background Art

[0002] The polymerizer reactor for self-assembly of active molecules of traditional Chinese medicine for sustained-release agents plays an important role in biopharmaceuticals. However, similar to natural medicines, the active components of traditional Chinese medicine are susceptible to various environmental factors such as pH value, solvent, light, temperature, humidity and metal ions during production, storage and use, which may cause physical or chemical reactions and change the overall quality of the medicine. Therefore, accurate control of the reaction parameters of the reactor is the key to ensuring the activity and yield of traditional Chinese medicine monomers.

[0003] In recent years, with the frequent occurrence of many livestock product safety issues such as veterinary drug residues, antibiotic abuse and drug resistance, the search for low-toxic, efficient and environmentally friendly natural drugs and sustained-release carriers for humans, livestock and poultry and the ecological environment has become a new research field and direction for scientific and technological workers, but there are still few Chinese medicine sustained-release carriers for clinical use. Therefore, the design of synthetic drug sustained-release system devices has become a hot topic in current research. The study of Chinese medicine component macromolecular imprinted polymers (MIPs) as drug delivery systems has become the focus of current modern pharmaceutical research. Drug release from MIPs is often regulated from the perspective of factors such as thermosensitivity, acidity and alkalinity, and endogenous substances. In particular, when acidity and alkalinity are used as regulatory factors, MIPs can directly release loaded active drug molecules by binding to endogenous substances through specific affinity, and can also indirectly achieve the targeting of active drug molecules by competitively replacing drug structural analogs. Ciardelli et al. prepared molecularly imprinted nanospheres through theophylline template free radical polymerization, which showed good theophylline recognition performance (up to 1 mg / g). The rebinding ability of theophylline was 5.1 times higher than that of caffeine, a compound with similar structure, and the drug release reached 95% of the drug loading within 7 days. Molecularly imprinted nanoparticles of traditional Chinese medicine salidroside, rhododendron, quercetin, etc. were synthesized successively, which had good sustained release effect, greatly improving the efficacy of traditional Chinese medicine on the basis of saving traditional Chinese medicine and maintaining the structural stability of active ingredients.

[0004] However, due to the particularity of the steps of mixing, evacuation, nitrogen filling, stirring, heating, pressurization, constant temperature, cooling, and cleaning required in the process of synthesizing the sustained-release active molecular agent of traditional Chinese medicine, it is difficult to conduct experiments on process control at the production site. Some studies have shown that after the raw materials of active components of traditional Chinese medicine are added, the heating is stopped when the predetermined reaction temperature is reached. However, there is a strong exothermic effect in the polymerization process, and the relationship between the heat release rate and the reaction temperature is positive feedback self-excitation. In other words, if there are some disturbances that increase the reaction temperature, the polymerization reaction rate will decrease, the heat release rate will increase, the reaction temperature will further increase, and even lead to the "implosion" phenomenon, which will reduce the swelling rate of the molecular imprinted nanoparticles in the entire kettle and turn them into waste, thereby affecting the drug effect. A polymerization reactor disclosed in the Chinese patent with patent number CN202111129144.3 includes a kettle body, a stirring structure and a nitrogen-filled structure; wherein the stirring structure and the nitrogen-filled structure are both arranged in the kettle body; the stirring structure is rotatably connected to the kettle body; the nitrogen-filled structure includes an air-filling unit for introducing nitrogen into the kettle body, and a lifting unit for driving the air-filling unit to lift; the air-filling unit is arranged around the outside of the stirring structure; one end of the lifting unit is connected to the kettle body, and the other end is connected to the air-filling unit. The polymerization reactor provided by the present invention, by setting the nitrogen-filled structure as a lifting structure, on the one hand, enables the nitrogen-filled structure to be filled with nitrogen and deoxygenated at different heights in the polymerization reactor, thereby improving the effect of nitrogen-filled and deoxygenated; on the other hand, nitrogen sealing is performed by the nitrogen-filled structure, which can achieve dual-purpose, maintain the stability of the reaction, and simplify the structure of the polymerization reactor. However, in the process of using the existing polymerization reactor, the stirring structure is prone to stirring dead angles during the stirring process of the materials, resulting in uneven mixing of the materials, affecting the stirring efficiency, and when different materials are stirred and mixed, the spacing between the stirring paddles is too small or too large, which will affect the mixing efficiency of the materials, resulting in insufficient work efficiency. At present, the polymerization reaction is usually mixed by the suspension method, through water and marine polysaccharide (chitooligosaccharide, laminarin, fucoidan, etc.) functional monomers, and then edible oil is added to destroy the original stable system, and then ethanol is added dropwise to make the unstable system stable. Because the density of the vegetable oil is small when adding the vegetable oil, the oil will be attached to the upper end of the solution. During the stirring process, the vegetable oil is first mixed with the upper part of the solution, and the waiting time for the solution at the bottom to contact and fuse with the oil is long, resulting in poor mixing uniformity and greatly increased polymerization reaction time.

[0005] Therefore, in order to solve the above technical problems, the present application designs a synthesis reactor for self-assembly of polymer nanocarriers of active components of traditional Chinese medicine. Summary of the invention

[0006] The purpose of the present invention is to provide a synthesis reactor for a macromolecular sustained-release agent of active components of traditional Chinese medicine, so as to solve the problems existing in the above-mentioned prior art, and realize the efficient utilization of active components of traditional Chinese medicine on the basis of energy saving and consumption reduction and reduction of raw material usage.

[0007] To achieve the above object, the present invention provides the following scheme: The present invention provides a synthesis reactor of a macromolecular sustained-release agent of active ingredients of traditional Chinese medicine, comprising:

[0008] A tank body, wherein a gas delivery component and a material delivery component are arranged on the end surface of the tank body, an intelligent constant temperature heating component is arranged on the side wall of the tank body, and a temperature control component is arranged inside the tank body;

[0009] A hollow reflux stirring assembly is arranged in the tank body, the stirring assembly includes a stirring rod and a plurality of hollow reflux stirring paddles fixed to the outer wall of the stirring rod, a plurality of spray holes are opened on the side wall of the hollow reflux stirring paddle, the spray holes are connected to the outside of the tank body through the stirring rod, and the spray holes are used to spray water or air;

[0010] A plugging member is movably disposed in the hollow reflux stirring paddle, and when the stirring rod is not ventilated or water is passed through, the plugging member is used to plug the plurality of the spray holes, and when the stirring rod is ventilated or water is passed through, the stirring rod is connected to the plurality of the spray holes;

[0011] A driving member is fixed on the top of the tank body, and the driving member is drivingly connected to the stirring rod.

[0012] Preferably, the tank body comprises a tank body with a sealed bottom end, a tank cover is detachably connected to the top of the tank body, the gas delivery assembly is arranged on the tank cover, and the driving member is fixed to the top of the tank cover.

[0013] Preferably, the hollow reflux agitator paddle is a plate body with an active cavity opened inside, the sealing member is located in the active cavity, a plurality of active grooves are opened on the inner wall of the side wall of the hollow reflux agitator paddle close to the sealing member, the spray hole is located in the active groove, the spray hole is connected to the active groove, and the end of the sealing member for sealing the spray hole is located in the active groove.

[0014] Preferably, the sealing member includes a sealing plate arranged in the active cavity, a plurality of sealing columns are fixedly connected to one side of the sealing plate close to the active groove, the sealing columns are located in the active groove, and the sealing columns are arranged corresponding to the spray holes and seal the spray holes, a compression spring is fixedly connected to one end of the sealing plate away from the stirring rod, and the other end of the compression spring is fixedly connected to the inner wall of the hollow reflux stirring paddle.

[0015] Preferably, the end surface of the hollow reflux stirring paddle close to the stirring rod extends into the stirring rod, the end surface of the hollow reflux stirring paddle close to the stirring rod is a limiting end surface, a limiting groove is provided on the limiting end surface, the cross-sectional area of ​​the limiting groove is smaller than the cross-sectional area of ​​the active cavity, and one end of the blocking plate close to the stirring rod matches the limiting groove;

[0016] When the stirring rod is not ventilated or water is flowing, the end of the blocking plate close to the stirring rod is located in the limiting groove. When the stirring rod is ventilated or water is flowing, the end of the blocking plate close to the stirring rod is separated from the limiting groove.

[0017] Preferably, one end of the stirring rod passes through the tank cover and extends out of the tank body, and the end surface of the stirring rod is connected to an input pipe through a rotary sealing joint, and the input pipe allows ventilation or water to flow into the stirring rod.

[0018] Preferably, the driving member includes a driving motor fixedly connected to the top end of the tank cover, the output end of the driving motor is transmission-connected to the outer wall surface of the stirring rod through a gear box, and the stirring rod is rotationally connected to the tank body through the driving motor.

[0019] Preferably, the gas delivery assembly includes a nitrogen pipe and a vacuum pipe fixedly connected to the top of the tank cover, the nitrogen pipe and the vacuum pipe are located on one side of the stirring rod, and the nitrogen pipe and the vacuum pipe are connected to the tank body.

[0020] Preferably, the feeding assembly includes a feed pipe and a discharge pipe, wherein the feed pipe is fixedly connected to the top end of the tank cover, the discharge pipe is fixedly connected to the bottom end of the tank body, and both the feed pipe and the discharge pipe are connected to the tank body.

[0021] Preferably, the heating assembly comprises a water inlet pipe and a water outlet pipe fixedly connected to the side wall of the tank body, a heating chamber is formed on the side wall of the tank body, and a water outlet end of the water inlet pipe and a water inlet end of the water outlet pipe are in communication with the heating chamber.

[0022] Compared with the prior art, the present invention has the following advantages and technical effects: the present invention discloses a reaction kettle for synthesizing polymer nanocarriers of active components of traditional Chinese medicine, which adopts a tank side wall heating component to heat the side wall in a cycle. After heating to a predetermined reaction temperature, a temperature control component is used to control the tank temperature to save energy, ensure accurate control of the polymerization reaction, meet the needs of sustained-release agent synthesis, and realize the synthesis of sustained-release agents of active molecules of traditional Chinese medicine; during the reaction, a driving member is used to drive a stirring rod to rotate, and the rotation of the stirring rod drives a hollow reflux stirring paddle to rotate, so as to stir the mixed liquid in the tank, so as to meet the stirring requirements in the synthesis process; at the same time, A plurality of spray holes are arranged on the side wall of the hollow reflux stirring paddle. When the sustained-release agent is synthesized, the spray holes are blocked by the plugging member, so that the hollow reflux stirring paddle can be used for stirring as well as for passing reaction solvent and cleaning agent into the hollow reflux stirring paddle. On the basis of driving the hollow reflux stirring paddle to rotate, the inner wall of the reactor is evacuated, nitrogen-filled and cleaned. On the basis of ensuring rapid and stable initiation of polymerization reaction, a continuous and stable synthesis, discharging and cleaning integrated system is realized, thereby achieving the purpose of stable synthesis of molecular imprinting carrier of traditional Chinese medicine and improving economic benefits. After the reaction is completed, a coolant is passed through the side wall jacket during the reaction process to quickly dissipate heat.

[0023] The present invention, based on optimizing the design of a kettle reactor, further utilizes an experimental model to evaluate the product synthesized by the reactor, and obtains molecularly imprinted nanoparticles with high purity and good swelling property. At the same time, the temperature control component and the reflux hollow reflux stirring paddle of the reactor itself are utilized to pass the reaction solvent and the cleaning agent into the hollow reflux stirring paddle, and intermittent feeding of the inner wall of the reactor and cleaning of the inner wall of the tank are performed on the basis of driving the hollow reflux stirring paddle to rotate. This invention has important application value for designing and realizing an automated system for the production process of polymer imprinted nanoparticles of active components of traditional Chinese medicine. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0025] Figure 1 is a three-dimensional diagram of a reactor;

[0026] Figure 2 It is a three-dimensional diagram of the tank cover and the tank body in a disassembled state;

[0027] Figure 3 is a three-dimensional diagram of a heating assembly;

[0028] Figure 4 A three-dimensional diagram of the connection between the stirring rod and the tank cover;

[0029] Figure 5 A three-dimensional diagram of the connection between the stirring rod and the hollow reflux stirring paddle;

[0030] Figure 6 A three-dimensional diagram of the blocking plate blocking the spray hole;

[0031] Figure 7 It is a three-dimensional picture of the state where the blocking plate does not block the spray hole;

[0032] Figure 8 An exploded view of the connection between the plugging plate and the hollow reflux stirring paddle;

[0033] Fig. 9 Schematic diagram of the positional relationship between the movable slot and the spray hole;

[0034] Fig.10 A schematic diagram of molecularly imprinted nanoparticles of active components of traditional Chinese medicine synthesized by a reactor simulation experiment of the present invention;

[0035] Fig.11 Schematic diagram of molecularly imprinted nanoparticles of traditional Chinese medicine active ingredients designed and synthesized using a common reactor;

[0036] Fig.12 Schematic diagram of the adsorption of different concentrations of salidroside by SCMIP1 and SCNIP2;

[0037] Fig.13 Schematic diagram of the adsorption kinetic curves of salidroside by SCMIP1 and SCMIP2 at different times;

[0038] Fig.14 Schematic diagram of the Scatchard model analysis for SCMIP1 and SCMIP2;

[0039] Fig.15 Schematic diagram of the cumulative release of salidroside from SCMIP1 and SCMIP2 in simulated gastric / intestinal fluid (37°C);

[0040] Fig.16 Schematic diagram of the fitting of salidroside in SCMIP1 and SCMIP2 in simulated gastric / intestinal fluid (37°C);

[0041] Among them, 1. stirring rod; 2. hollow reflux stirring paddle; 3. spray hole; 4. tank body; 5. tank cover; 6. movable cavity; 7. movable groove; 8. sealing plate; 9. sealing column; 10. compression spring; 11. limit end face; 12. limit groove; 13. rotary sealing joint; 14. input pipe; 15. drive motor; 16. gear box; 17. nitrogen pipe; 18. vacuum pipe; 19. feed pipe; 20. discharge pipe; 21. water inlet pipe; 22. water outlet pipe; 23. heating chamber; 24. support; 25. connecting plate; 26. inclined surface. DETAILED DESCRIPTION

[0042] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0043] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0044] Reference Figure 1-9 The present invention provides a synthesis reactor of a macromolecular nanocarrier of a traditional Chinese medicine active component, comprising:

[0045] The tank body has a gas delivery component and a material delivery component on its end surface, an intelligent constant temperature heating component on its side wall, and a temperature control component inside the tank body;

[0046] The hollow reflux stirring assembly is arranged in the tank body, and the stirring assembly includes a stirring rod 1 and a plurality of hollow reflux stirring paddles 2 fixed to the outer wall of the stirring rod 1. A plurality of spray holes 3 are opened on the side wall of the hollow reflux stirring paddle 2. The spray holes 3 are connected to the outside of the tank body through the stirring rod 1, and the spray holes 3 are used for spraying water or air.

[0047] The plugging member is movably arranged in the hollow reflux stirring paddle 2. When the stirring rod 1 is not ventilated or water is passed through, the plugging member is used to block the plurality of spray holes 3. When the stirring rod 1 is ventilated or water is passed through, the stirring rod 1 is connected with the plurality of spray holes 3.

[0048] The driving member is fixed on the top of the tank body, and is drivingly connected to the stirring rod 1.

[0049] During the synthesis of the sustained-release agent, the material is fed into the tank through the material feeding component, and gas is fed or extracted into the tank through the gas feeding component, so that the tank meets the synthesis requirements. The tank is heated by the heating component to meet the synthesis temperature requirements, and the driving member drives the stirring rod 1 to rotate, and the stirring rod 1 drives multiple hollow reflux stirring paddles 2 to rotate to stir the synthetic material in the tank. When the synthesis is completed and the synthetic material is led out, the reaction solvent and the cleaning agent are introduced into the end of the stirring rod 1 located outside the tank, and the reaction solvent and the cleaning agent enter The plugging piece is squeezed into the stirring rod 1, and the plugging piece moves and releases the blockage of the spray hole 3. At the same time, the plugging piece moves, so that the reaction solvent and the cleaning agent enter the hollow reflux stirring paddle 2, and are sprayed onto the inner wall of the tank body through a plurality of spray holes 3 to flush the inner wall of the tank body. After the flushing is completed, the waste water is discharged, and high-temperature air is introduced into the stirring rod 1. The high-temperature air is discharged from the spray hole 3 through the stirring rod 1 and the hollow reflux stirring paddle 2 to dry the inner wall of the tank body. The above process does not require the installation of an additional cleaning device in the tank body, and its cleaning efficiency is high.

[0050] Specifically, for example, in the preparation process of aminated Fe3O4 / SiO2 paramagnetic nanoparticles, Fe3O4@SiO2 microspheres were prepared by sol-gel method, in which the mixed solution needs to be stirred and reacted continuously at room temperature for 24 hours, and needs to be incubated under nitrogen protection for 5 hours. In this process, the mixed solution needs to be placed in a tank and reacted under predetermined temperature and gas conditions, so a gas transmission component and a heating component are set. Further, based on the analysis of the temperature dynamic characteristics during the reaction process, the basic model of the object transfer function is determined, and then the data obtained by the simulation experiment is used for identification, and the open-loop control model is established to meet the actual needs of synthesizing Chinese medicine molecular imprinting nanoparticles, as shown in Table 1 for details.

[0051] Table 1. Comparison of simulation experiments on molecularly imprinted nanoparticles of active components of synthetic traditional Chinese medicine

[0052]

[0053] Reference Fig.10 The salidroside molecularly imprinted nanoparticles (SCMIP1) synthesized by the reactor designed by the present invention using gel permeation chromatography, high performance liquid chromatography, transmission electron microscopy and other technologies have the characteristics of uniform morphology and reasonable size. The product yield is 74±2.23%, the drug loading is 371 mg / g, and the saturated swelling rate is 67±2.12%.

[0054] Reference Fig.11 The salidroside molecularly imprinted nanoparticles (SCMIP2) synthesized without using the reactor of this design were not uniform in size and had poor dispersibility in the solvent. The product yield was 14±2.14% with a drug loading of 130 mg / g and a swelling rate of 44±6.25%.

[0055] Furthermore, in order to study the reactor designed by the present invention, we measured the binding amount of SMCMIP and SMCNIP after the adsorption reached equilibrium at room temperature, and explained the equilibrium concentration C e .like Fig.12 As shown in Figure 2, when the concentration exceeds 5 mg / mL, the adsorption of salidroside by SCMIP1 is significantly higher than that by SCMIP2. Fig.13 As shown in the figure, the adsorption of SCMIP2 is more non-specific, the adsorption of SCMIP1 to salidroside increases with time and reaches equilibrium after 20 minutes, while SCMIP2 reaches equilibrium after 5 minutes. Further Scatchard analysis was performed, and SCMIP1 showed a special adsorption process. The adsorption capacity can be mainly attributed to two specific binding sites. The maximum adsorption capacity Q max The value is 371 mg / g, while the adsorption of SCMIP2 is nonspecific and irregular.

[0056] For the binding amount Q of the target molecule and its analogs, the Scatchard equation was used to study the binding characteristics of the imprinted polymer and the template molecule. e Mapped to the Q of salidroside, the Q of the polymer sample was obtained max , where Q is the adsorption amount; C0 and C e are the sample concentrations in the solution before and after adsorption, respectively; K d is the dissociation constant.

[0057] Reference Fig.14 In the figure, the two straight lines with obvious nonlinear relationship indicate that the binding sites of the imprinted polymer are not completely equivalent to the imprinted molecules, and there are two different binding sites. The two linear parts in the figure are fitted to obtain the fitting of the linear equation, that is, the high affinity and low affinity site equations.

[0058] The diffusion characteristics and release kinetics of SCMIP1 and SCMIP2 were studied using mathematical models such as Higuchi (1) and Korsmeyer-Peppas (2), which are expressed in the following formulas.

[0059]

[0060] Where A is the Higuchi constant that reflects the characteristics of the formula. This model is mainly applicable to the kinetic study of drug diffusion into the medium in a planar substrate or porous polymer, and the matrix is ​​reasonably assumed to be insoluble.

[0061]

[0062] Where K is the release kinetic constant and n is the characteristic exponent related to the drug diffusion mechanism. This model is applicable to the release stage with cumulative release rate <60%, that is, Mt / M∞<0.6.

[0063] Through in vitro release studies of SCMIP1 and SCMIP2, Fig.15 and Fig.16 As shown, for SCMIP1, the release in simulated gastric fluid (reaching 50% at 6 h) was faster than that in intestinal fluid (close to or below 50% at 18 h). However, the salidroside release performance of SCMIP2 was not sensitive to changes in pH. The rapid release rate of the drug under acidic pH conditions may be due to the high solubility of the drug at this pH. The affinity of salidroside for the lumen of SCMIP1 was weakened because the hydrogen ions in the release medium had to compete with the acrylic acid groups (pKa = 4.5). These factors promoted the rapid release of the drug under acidic conditions. In simulated gastric fluid (pH = 1.5), the polymer hydroxyl groups from salidroside and CC were ionized. The high ionic strength overcame the electrostatic interaction between salidroside and the polymer to promote the release. However, the limited affinity of the drug to CC may produce some ionic effects, and the control of the matrix release process in the simulated fluid at pH = 7.4 was weak. In this group, the salidroside release rate of CC in the network polymer met the requirements of sustained release. After analyzing and measuring the carriers SCMIP1 and SCMIP2 at 25°C and 37°C, the salidroside content in the extract of each sample was measured to be approximately 77% and 86%, respectively. Compared with SCMIP2, 37°C is more conducive to the release of salidroside, with the release rates reaching 86% and 77%, respectively. This may be because the SCMIP1 synthesized by the reactor designed by the invention is more conducive to the release of salidroside. Therefore, the SCMIP1 synthesized by the reactor designed by the invention can be used to control the release time of salidroside in traditional Chinese medicine, thereby improving the application effect of the drug.

[0064] Furthermore, two groups of hollow reflux stirring paddles 2 can be provided, each group is composed of multiple hollow reflux stirring paddles 2 located on the same vertical plane, and the positions of the spray holes 3 on the multiple hollow reflux stirring paddles 2 located on the same vertical plane can be adjusted, so that the spray holes 3 on the multiple hollow reflux stirring paddles 2 on the same vertical plane can simultaneously clean a vertical surface of the inner wall of the tank. This arrangement can reduce cleaning dead angles and improve the cleaning effect.

[0065] According to a further optimized solution, the tank body includes a tank body 4 with a sealed bottom end, a tank cover 5 is detachably connected to the top of the tank body 4, a gas delivery component is arranged on the tank cover 5, and a driving member is fixed to the top of the tank cover 5.

[0066] Furthermore, a support 24 is fixedly connected to the side wall of the tank body 4. The support 24 is used to support the tank body 4 to facilitate its placement.

[0067] Further, the outer wall of the tank cover 5 and the outer wall at the top of the tank body 4 are both fixedly connected with a connecting plate 25, the two connecting plates 25 match, and the two connecting plates 25 are detachably connected by a number of connecting bolts. Under the action of the connecting bolts and the connecting plate 25, the tank cover 5 and the tank body 4 are detachably connected, and the purpose is to facilitate the separation of the stirring assembly from the tank body 4. After being used for a long time, the stirring rod 1 and the hollow reflux stirring paddle 2 need to be maintained or replaced, so the tank cover 5 is disassembled to complete the disassembly of the stirring rod 1 and the hollow reflux stirring paddle 2. In addition, the inner wall of the tank body 4 can be effectively cleaned by using the hollow reflux stirring paddle 2, but due to the position setting of the hollow reflux stirring paddle 2, there may be dead corners on the hollow reflux stirring paddle 2 that cannot be cleaned, so the tank cover 5 is set to be separable from the tank body 4. After cleaning and drying, the stirring rod 1 and the hollow reflux stirring paddle 2 can be taken out and manually cleaned.

[0068] Further optimization scheme, the hollow reflux stirring paddle 2 is a plate body with an active cavity 6 opened inside, the plugging piece is located in the active cavity 6, a plurality of active grooves 7 are opened on the inner wall of the side wall of the hollow reflux stirring paddle 2 close to the plugging piece, the spray hole 3 is located in the active groove 7, the spray hole 3 is connected with the active groove 7, and the end of the plugging piece used to plug the spray hole 3 is located in the active groove 7. Under the pressure of external water or wind, the plugging piece moves in the active cavity 6, so as to controllably block or unblock the spray hole 3. When water or ventilation is not passed, the blocking part of the blocking piece is located in the spray hole 3, so that the composition in the tank body 4 is not easy to enter the active cavity 6. When water or ventilation is passed, the blocking part of the blocking piece moves in the active groove 7, and the spray hole 3 is exposed at this time.

[0069] Furthermore, the side wall of the hollow reflux stirring paddle 2 close to the plugging member is an inclined surface 26, and the top width of the hollow reflux stirring paddle 2 is smaller than the bottom width of the hollow reflux stirring paddle 2. The purpose of setting the inclined surface 26 is, on the one hand, to facilitate the setting of the spray hole 3, so that the spray hole 3 sprays water or air in an oblique upward direction, and on the other hand, the existence of the inclined surface 26 allows heavy particles or materials to be transported upward through the inclined surface 26 during the synthesis of the sustained-release agent, so as to facilitate the mixing of the particles or materials.

[0070] A further optimized solution is that the sealing part includes a sealing plate 8 arranged in the movable cavity 6, and a plurality of sealing columns 9 are fixedly connected to one side of the sealing plate 8 close to the movable groove 7. The sealing columns 9 are located in the movable groove 7, and the sealing columns 9 are arranged corresponding to the spray hole 3 and seal the spray hole 3. A compression spring 10 is fixedly connected to one end of the sealing plate 8 away from the stirring rod 1, and the other end of the compression spring 10 is fixedly connected to the inner wall of the hollow reflux stirring paddle 2. The blocking column 9 is used to block the spray hole 3. When ventilation or water is not passed to the stirring rod 1, under the action of the compression spring 10, a force is applied to the blocking plate 8 in the direction of the stirring rod 1. The blocking column 9 is located on one side of the movable groove 7. At the same time, the blocking column 9 blocks the spray hole 3 at this position. When ventilation or water is passed to the stirring rod 1, the compression spring 10 is compressed under the action of external pressure, so that the blocking column 9 leaves the spray hole 3 and moves in the movable groove 7. When the blocking column 9 approaches and contacts the other side of the movable groove 7, it stops moving. At this time, the stirring rod 1 is connected to the spray hole 3 through the active cavity 6, and the reaction solvent and cleaning agent or high-temperature air can be sprayed into the tank body 4 through the spray hole 3.

[0071] A further optimized solution is that the end face of the hollow reflux stirring paddle 2 close to the stirring rod 1 extends into the stirring rod 1, and the end face of the hollow reflux stirring paddle 2 close to the stirring rod 1 is a limiting end face 11, and a limiting groove 12 is provided on the limiting end face 11, and the cross-sectional area of ​​the limiting groove 12 is smaller than the cross-sectional area of ​​the active cavity 6, and the end of the sealing plate 8 close to the stirring rod 1 matches the limiting groove 12; when there is no ventilation or water flowing in the stirring rod 1, the end of the sealing plate 8 close to the stirring rod 1 is located in the limiting groove 12, and when ventilation or water is flowing in the stirring rod 1, the end of the sealing plate 8 close to the stirring rod 1 is separated from the limiting groove 12. The existence of the limiting end face 11 supports the sealing plate 8 and at the same time seals the connection between the hollow reflux stirring paddle 2 and the stirring rod 1. In addition, the existence of the limiting groove 12 limits the sealing plate 8. When supporting stirring, the existence of the limiting groove 12 prevents the sealing plate 8 from shifting. Therefore, the sealing plate 8 can prevent the sealing column 9 from leaving the spray hole 3. This setting can better prevent the synthetic material from entering the hollow reflux stirring paddle 2, avoiding waste of the synthetic material and blocking of the hollow reflux stirring paddle 2.

[0072] When ventilation or water is allowed to flow outside, the pressure inside the stirring rod 1 increases, and the high-temperature gas or high-pressure liquid squeezes the end of the sealing plate 8. The end of the sealing plate 8 moves and exposes the connection between the hollow reflux stirring paddle 2 and the stirring rod 1, thereby allowing the high-temperature gas or high-pressure liquid to flow normally.

[0073] Furthermore, during stirring, air can be evacuated from the stirring rod 1 to form a negative pressure inside the stirring rod 1 . In this arrangement, the blocking plate 8 cannot move away from the stirring rod 1 , thereby preventing the blocking column 9 from detaching from the spray hole 3 .

[0074] In an optional embodiment of the present invention, according to the strength of the compression spring 10, when the blocking plate 8 is out of the limiting groove 12, the strength of the compression spring 10 is sufficient to support the blocking plate 8, so that the blocking plate 8 does not deviate and can re-enter the limiting groove 12 after the compression spring 10 is reset, and there is no need to make too many settings on the structure of the blocking plate 8.

[0075] In another optional embodiment of the present invention, according to the strength of the compression spring 10, when the sealing plate 8 is separated from the limiting groove 12, the strength of the compression spring 10 is not sufficient to support the sealing plate 8. In this case, a number of support rods (not shown in the figure) can be fixed to the outer wall of the sealing plate 8, and a slide groove is opened on the inner wall of the hollow reflux agitator 2. The end of the support rod is slidably connected to the inner wall of the hollow reflux agitator 2 through the slide groove, which is used to support the sealing plate 8 to prevent the sealing plate 8 from deviating after being separated from the limiting groove 12 and becoming unable to be reset.

[0076] In a further optimized solution, one end of the stirring rod 1 passes through the tank cover 5 and extends out of the tank body 4, and the end face of the stirring rod 1 is connected to the input pipe 14 through a rotary sealing joint 13, and the input pipe 14 allows ventilation or water to flow into the stirring rod 1. Under the action of the rotary sealing joint 13, the stirring rod 1 can rotate relative to the input pipe 14, and at the same time, the input pipe 14 can pass high-pressure liquid or high-temperature gas into the stirring rod 1, and the feed end of the input pipe 14 is manually controlled to feed liquid or gas.

[0077] Further optimizing the scheme, the driving member includes a driving motor 15 fixed to the top of the tank cover 5, the output end of the driving motor 15 is connected to the outer wall of the stirring rod 1 through the gear box 16, and the stirring rod 1 is connected to the tank body 4 through the driving motor 15. The driving motor 15 is fixed to the top of the tank cover 5, and it forms an integral structure with the tank cover 5, and can move with the tank cover 5. The gear box 16 is a gearbox, and the output end of the driving motor 15 drives the stirring rod 1 to rotate under the action of the gear box 16.

[0078] Further optimizing the scheme, the gas delivery assembly includes a nitrogen pipe 17 and a vacuum pipe 18 fixedly connected to the top of the tank cover 5, the nitrogen pipe 17 and the vacuum pipe 18 are located on one side of the stirring rod 1, and the nitrogen pipe 17 and the vacuum pipe 18 are connected to the tank body 4. The nitrogen pipe 17 is used to input nitrogen into the tank body 4, and the vacuum pipe 18 is used to vacuum the tank body 4.

[0079] Furthermore, a pressure sensor (not shown in the figure) is fixedly connected to the inner wall of the tank body 4, and the pressure sensor is used to monitor the internal pressure of the tank body 4 to meet the synthesis requirements.

[0080] Further optimized solution, the feeding assembly includes a feed pipe 19 and a discharge pipe 20, wherein the feed pipe 19 is fixedly connected to the top of the tank cover 5, and the discharge pipe 20 is fixedly connected to the bottom of the tank body 4, and both the feed pipe 19 and the discharge pipe 20 are connected to the tank body 4. The feed pipe 19 is used for feeding, and it is installed at the top of the tank cover 5, and the discharge pipe 20 is used for discharging, and it is installed at the bottom of the tank body 4.

[0081] Further optimization scheme, the heating assembly includes a water inlet pipe 21 and a water outlet pipe 22 fixedly connected to the side wall of the tank body 4, and a heating chamber 23 is opened on the side wall of the tank body 4. The water outlet end of the water inlet pipe 21 and the water inlet end of the water outlet pipe 22 are connected to the heating chamber 23. When heating, a water bath heating method is adopted. A heating box is arranged outside the tank body 4 to provide liquid with a certain temperature. The water inlet pipe 21 is located below the water outlet pipe 22, so that the liquid flows from bottom to top.

[0082] Furthermore, a temperature sensor (not shown in the figure) is fixedly connected to the inner wall of the tank body 4, and the temperature sensor is used to monitor the internal temperature of the tank body 4 to meet the synthesis requirements. An intelligent control terminal can be set outside, and the outputs of the nitrogen pipe 17, the vacuum pipe 18, and the water bath are all controlled by the intelligent control terminal, so that the reactor can be operated intelligently.

[0083] Specifically, during the synthesis of the sustained-release agent, the material is fed into the tank body 4 through the feed pipe 19, and gas is fed or exhausted into the tank body 4 through the nitrogen pipe 17 and the vacuum pipe 18, so that the tank body 4 meets the synthesis requirements. A liquid at a certain temperature is introduced into the heating chamber 23 to heat the tank body so that it meets the synthesis temperature requirements. The driving motor 15 drives the stirring rod 1 to rotate, and the stirring rod 1 drives the plurality of hollow reflux stirring paddles 2 to rotate to stir the synthetic material in the tank body 4. When the synthesis is completed and the synthetic material is led out, the reaction solvent and the cleaning agent are introduced into the input pipe 14 located in the tank body 4, and the reaction solvent and cleaning agent enter the stirring rod 1 and squeeze the blocking plate 8. The blocking plate 8 moves and allows the blocking column 9 to release the blocking of the spray hole 3. At the same time, the blocking plate 8 moves, allowing the reaction solvent and the cleaning agent to enter the hollow reflux stirring paddle 2, and are sprayed onto the inner wall of the tank body 4 through a plurality of spray holes 3 to rinse the inner wall of the tank body 4. After the flushing is completed, the waste water is discharged through the discharge pipe 20, and high-temperature air is introduced into the stirring rod 1. The high-temperature air is discharged from the spray hole 3 through the stirring rod 1 and the hollow reflux stirring paddle 2 to dry the inner wall of the tank body 4. The above process does not require the installation of an additional cleaning device in the tank body 4, and its cleaning efficiency is high.

[0084] In the description of the present invention, it should be understood that the terms "longitudinal", "lateral", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside" and "outside" etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present invention.

[0085] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A synthesis reactor of polymer nanocarriers of active ingredients of traditional Chinese medicine, Features: It comprises a tank body, a gas delivery component and a material delivery component are arranged on the end surface of the tank body, an intelligent constant temperature heating component is arranged on the side wall of the tank body, and a temperature control component is arranged inside the tank body; A hollow reflux stirring assembly is arranged in the tank body, the stirring assembly comprises a stirring rod (1) and a plurality of hollow reflux stirring paddles (2) fixed on the outer wall of the stirring rod (1), a plurality of spray holes (3) are opened on the side wall of the hollow reflux stirring paddle (2), the spray holes (3) are connected with the outside of the tank body through the stirring rod (1), and the spray holes (3) are used to spray water or air; a blocking member is movably arranged in the hollow reflux stirring paddle (2), when the stirring rod (1) is not ventilated or water is not flowing, the blocking member is used to block the plurality of spray holes (3), when the stirring rod (1) is ventilated or water is flowing, the stirring rod (1) is connected with the plurality of spray holes (3); a driving member is fixed on the top of the tank body, and the driving member is connected to the stirring rod (1) in a transmission manner.

2. The synthesis reactor of the macromolecular nanocarrier of the active ingredient of traditional Chinese medicine according to claim 1, Features: The tank body comprises a tank body (4) with a sealed bottom end, the top of the tank body (4) is detachably connected to a tank cover (5), the gas delivery assembly is arranged on the tank cover (5), and the driving member is fixed to the top of the tank cover (5).

3. The synthesis reactor of the macromolecular nanocarrier of the active ingredient of traditional Chinese medicine according to claim 1, Features: The hollow reflux stirring paddle (2) is a plate body with an active cavity (6) formed therein, the blocking member is located in the active cavity (6), a plurality of active grooves (7) are formed on the inner wall of the side wall of the hollow reflux stirring paddle (2) close to the blocking member, the spray hole (3) is located in the active groove (7), the spray hole (3) is connected to the active groove (7), and the end of the blocking member used for blocking the spray hole (3) is located in the active groove (7).

4. The synthesis reactor of the macromolecular nanocarrier of the active ingredient of traditional Chinese medicine according to claim 3, Features: The blocking member comprises a blocking plate (8) arranged in the movable cavity (6), and a plurality of blocking columns (9) are fixedly connected to one side of the blocking plate (8) close to the movable groove (7), and the blocking columns (9) are located in the movable groove (7), and the blocking columns (9) are arranged corresponding to the spray hole (3) and block the spray hole (3), and a compression spring (10) is fixedly connected to one end of the blocking plate (8) away from the stirring rod (1), and the other end of the compression spring (10) is fixedly connected to the inner wall of the hollow reflux stirring paddle (2).

5. The synthesis reactor of the macromolecular nanocarrier of the active ingredient of traditional Chinese medicine according to claim 4, Features: The end surface of the hollow reflux stirring paddle (2) close to the stirring rod (1) extends into the stirring rod (1); the end surface of the hollow reflux stirring paddle (2) close to the stirring rod (1) is a limiting end surface (11); a limiting groove (12) is provided on the limiting end surface (11); the cross-sectional area of ​​the limiting groove (12) is smaller than the cross-sectional area of ​​the active cavity (6); and one end of the sealing plate (8) close to the stirring rod (1) matches the limiting groove (12); When ventilation or water is not passed through the stirring rod (1), the end of the blocking plate (8) close to the stirring rod (1) is located in the limiting groove (12); when ventilation or water is passed through the stirring rod (1), the end of the blocking plate (8) close to the stirring rod (1) is separated from the limiting groove (12).

6. The synthesis reactor of the macromolecular nanocarrier of the active ingredient of traditional Chinese medicine according to claim 2, Features: One end of the stirring rod (1) passes through the tank cover (5) and extends out of the tank body (4), and the end surface of the stirring rod (1) is connected to an input pipe (14) via a rotary sealing joint (13), and the input pipe (14) allows ventilation or water to flow into the stirring rod (1).

7. The synthesis reactor of the macromolecular nanocarrier of the active ingredient of traditional Chinese medicine according to claim 2, Features: The driving member comprises a driving motor (15) fixedly connected to the top end of the tank cover (5); an output end of the driving motor (15) is transmission-connected to the outer wall surface of the stirring rod (1) via a gear box (16); and the stirring rod (1) is rotationally connected to the tank body (4) via the driving motor (15).

8. The synthesis reactor of the macromolecular nanocarrier of the active ingredient of traditional Chinese medicine according to claim 2, Features: The gas delivery assembly comprises a nitrogen pipe (17) and a vacuum pipe (18) fixedly connected to the top of the tank cover (5); the nitrogen pipe (17) and the vacuum pipe (18) are located on one side of the stirring rod (1), and the nitrogen pipe (17) and the vacuum pipe (18) are connected to the inside of the tank body (4).

9. The synthesis reactor of the macromolecular nanocarrier of the active ingredient of traditional Chinese medicine according to claim 2, Features: The feeding assembly comprises a feed pipe (19) and a discharge pipe (20), wherein the feed pipe (19) is fixedly connected to the top end of the tank cover (5), and the discharge pipe (20) is fixedly connected to the bottom end of the tank body (4), and both the feed pipe (19) and the discharge pipe (20) are connected to the inside of the tank body (4).

10. The synthesis reactor of the macromolecular nanocarrier of the active ingredient of traditional Chinese medicine according to claim 2, Features: The heating assembly comprises a water inlet pipe (21) and a water outlet pipe (22) fixedly connected to the side wall of the tank body (4); a heating chamber (23) is provided on the side wall of the tank body (4); a water outlet end of the water inlet pipe (21) and a water inlet end of the water outlet pipe (22) are in communication with the heating chamber (23).

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