Drug delivery bionic device, structural design and preparation method

Abstract

The invention provides a drug delivery bionic device, structural design and a preparation method, and belongs to the technical field of biomedical treatment instruments.The drug delivery bionic device comprises a driving module and a drug delivery module, the drug delivery module is fixedly connected with the driving module, the driving module comprises a plurality of monomers which are sequentially connected, the monomers are made of elastic materials, and the elastic materials are arranged in the driving module. Each single body comprises a top plate, a bottom plate, first inclined plates and second inclined plates, the outer side face of the top plate is fixedly connected with the first inclined plates, the outer side face of the bottom plate is fixedly connected with the second inclined plates, and the ends, away from the top plate, of the first inclined plates are fixedly connected with the ends, away from the bottom plate, of the second inclined plates. According to the bionic drug delivery device, intestinal tract movement is used as driving force, the bionic drug delivery device moves forwards by means of the intestinal tract movement, safe drug delivery of the intestinal tract is achieved according to the movement condition of the bionic drug delivery device in the intestinal tract, the overall structure is simple, and medical accidents are reduced.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical therapeutic instruments, and in particular to a drug delivery bionic device, a structural design and a preparation method. Background Art

[0002] With the development of biotechnology, there are more and more biological preparations based on oligonucleotides, proteins, peptides and other macromolecules. The route of administration is a common problem encountered by biological preparations in clinical applications. In the history of human pharmacological treatment, oral administration has always been the preferred route of administration. Oral administration of biological preparations is very easy to degrade in the biochemical environment of the gastrointestinal tract, and due to the conservative absorption selectivity of the gastrointestinal tract, biological preparations cannot be transported through the mucus or cell layer. The utilization of biological preparations through oral administration is limited, about 1%; it is difficult to maintain a stable blood drug concentration in the body when injecting biological preparations, and frequent injections will also cause great inconvenience and pain to the recipients, and often lead to poor patient compliance; transdermal administration is also restricted by the large molecular weight of biological preparations, and it is difficult to penetrate through the stratum corneum of the skin into the human circulatory system.

[0003] With the development of biomedical engineering, oral delivery technologies for biologics have been developed, such as mucosal adhesive patches, resident hydrogels, microdevices, and particle-based platforms. These methods can increase the local concentration of biologics and prolong the drug release period, but physiological barriers still exist and clinical efficacy remains to be verified. Therefore, how to overcome the difficulties of oral administration of biologics and improve patient compliance remains a huge challenge.

[0004] In recent years, new drug delivery systems have become a research hotspot. Their goal is to deliver biological drugs to the target accurately and efficiently, improve efficacy and reduce toxic side effects. Among them, the development of digestive tract drug delivery systems, especially intestinal drug delivery systems, is of great significance for the treatment of diseases such as inflammatory bowel disease and colorectal cancer. In the research of new drug delivery systems, people are obsessed with designing some integrated diagnosis and treatment drug delivery capsules. How to drive the capsule to move in the body and how to release drugs are particularly critical. At present, the driving methods for drug delivery capsules include electromagnetic field drive, hydraulic drive and computer remote drive. These driving methods will use a variety of electrical components, such as sensors, stepper motors, wireless transceivers and batteries. The driving device has a complex structure and many medical accidents, such as improper pneumatic pressure control, external high-frequency generator radio frequency causing harm to the human body, and unstable electric power source causing jamming or accidental release of drugs. Therefore, we propose a drug delivery bionic device, structural design and preparation method. Summary of the invention

[0005] The object of the present invention is to provide a drug delivery bionic device, a structural design and a preparation method to solve the problems raised in the above-mentioned background technology.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] The present invention provides a drug delivery bionic device, including a driving module and a drug delivery module. The drug delivery module is fixedly connected to the driving module. The driving module includes a number of monomers connected in sequence. The monomers are made of elastic materials. Each monomer includes a top plate, a bottom plate, a first inclined plate and a second inclined plate. The outer side surface of the top plate is fixedly connected to a number of first inclined plates. The outer side surface of the bottom plate is fixedly connected to a number of second inclined plates. One end of the first inclined plate away from the top plate is fixedly connected to one end of the second inclined plate away from the bottom plate.

[0008] Further, the drug delivery module includes a drug delivery capsule. A number of micropores for releasing drugs are provided at one end of the drug delivery capsule away from the driving module.

[0009] Further, the diameter of the micropores is 0.5 - 1 mm.

[0010] Further, the structural design parameters of the driving module include: the number of monomers, the size of the top plate, the angle β between the first inclined plate and the normal line perpendicular to the axis of the monomer, and the angle ɑ between the second inclined plate and the normal line perpendicular to the axis of the monomer.

[0011] Further, the top surface and the bottom surface of the top plate are both square in shape. The size of the top plate is the side length H of the square. The range of the side length H is 1 - 10 mm. The range of the number of monomers is 3 - 5. The range of the angle ɑ is 25 - 50°. The range of the angle β is 0 - 25°.

[0012] The present invention also provides a structural design of a drug delivery bionic device. The structural design is used to design the above-mentioned drug delivery bionic device, including: determining the structural design parameters of the drug delivery bionic device, obtaining the optimal numerical range of each parameter through the method of controlling variables and finite element analysis, and then obtaining the optimal solution of each parameter through an orthogonal test with four factors and three levels.

[0013] Further, it includes the following steps:

[0014] S1: Select the number of monomers, the size of the top plate, the angle β between the first inclined plate and the normal line perpendicular to the axis of the monomer, and the angle ɑ between the second inclined plate and the normal line perpendicular to the axis of the monomer as the structural design parameters of the drug delivery bionic device, and then determine the numerical range of each parameter;

[0015] S2: Conduct single-factor analysis through the method of controlling variables, and then combine with finite element analysis to obtain the single-factor analysis results, that is, the optimal numerical range of each structural design parameter;

[0016] S3: Design a four-factor and three-level orthogonal experiment, set up nine groups of experiments, and obtain the optimal solution of each structural design parameter by comparing the displacement of the drug delivery bionic device.

[0017] The present invention also provides a preparation method of a drug delivery bionic device, which is used to prepare the above-mentioned drug delivery bionic device, and includes the following steps:

[0018] Including the following steps:

[0019] S1: Prepare the driving module: Use 3D printing technology to prepare the driving module;

[0020] S2: Prepare the drug delivery module

[0021] S21: Process the drug delivery capsule, then process micropores on the drug delivery capsule, and perform plasma treatment on the inner wall of the micropores after processing;

[0022] S22: Configure a pH-sensitive hydrogel solution;

[0023] S23: Inject the hydrogel solution into the cavity of the drug delivery capsule, then place the drug delivery capsule in a vacuum chamber to remove air bubbles, and then perform ultraviolet curing treatment. After the treatment, remove the excess gel and residues;

[0024] S24: Inject the drug into the cavity of the drug delivery capsule, and then seal the drug delivery capsule. After sealing, perform an airtightness test;

[0025] S25: After completion, perform sterilization treatment on the drug delivery capsule, and perform packaging in a sterile environment after the treatment;

[0026] S3: Assemble the driving module and the drug delivery module.

[0027] Further, the step S1 specifically includes:

[0028] S11: Use modeling software to design the driving module model;

[0029] S12: Import the driving module model into the slicing software, set the printing parameters in the slicing software. After the parameter setting is completed, use the slicing software to slice the model, generate a file recognized by the printing platform, and send the file to the printing platform;

[0030] S13: The printing platform prints the driving module;

[0031] S14: After printing is completed, turn off the printing platform. Wait for the part to cool to room temperature and then remove it. Process the surface of the part according to the design requirements.

[0032] Further, the step S22 specifically includes: using polyacrylic acid with a concentration of 6% as a matrix, adding polyethylene glycol diacrylate with a concentration of 2% as a crosslinking agent, and incorporating a photoinitiator with a concentration of 0.1% to form a mixed solution, and stirring the mixed solution until it is uniform to obtain a pH-sensitive hydrogel solution.

[0033] Compared with the prior art, the present invention has the following technical effects:

[0034] In the present invention, intestinal peristalsis is coordinated involuntary intestinal contraction and relaxation. Human intestinal peristalsis has about 10 radial contractions per minute, and the compression force is about 0.18 - 0.5 N / cm. This drug delivery bionic device uses intestinal peristalsis as a driving force, advances by deforming with intestinal peristalsis, and realizes safe drug delivery to the intestine by observing its movement in the intestine. The overall structure is simple, reducing the occurrence of medical accidents. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 It is a schematic structural diagram of the drug delivery bionic device according to an embodiment of the present invention;

[0036] Figure 2 It is a schematic structural diagram of the drug delivery bionic device according to an embodiment of the present invention from another angle;

[0037] Figure 3 It is a schematic structural diagram of the monomer according to an embodiment of the present invention;

[0038] Figure 4 It is a schematic structural diagram of the drive module according to an embodiment of the present invention;

[0039] Figure 5 It is a scatter plot of factor ɑ in the single-factor analysis according to an embodiment of the present invention;

[0040] Figure 6 It is a scatter plot of factor β in the single-factor analysis according to an embodiment of the present invention;

[0041] Figure 7 It is a scatter plot of factor H in the single-factor analysis according to an embodiment of the present invention;

[0042] Figure 8 It is a scatter plot of the number of monomers in the single-factor analysis according to an embodiment of the present invention;

[0043] Figure 9 It is a cloud diagram of the displacement of nine experimental groups under the orthogonal test of the drug delivery bionic device according to an embodiment of the present invention;

[0044] Figure 10 It is a cloud diagram of the displacement of the optimal solution under the orthogonal test of the drug delivery bionic device according to an embodiment of the present invention.

[0045] In the figure: 1. Driving module; 11. Monomer; 111. Top plate; 112. First inclined plate; 113. Bottom plate; 114. Second inclined plate; 2. Medicine delivery module; 21. Medicine delivery capsule; 22. Micropore; 3. Connecting piece. Detailed implementation mode

[0046] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0047] In this article, terms such as "left, right, up, down, front, back" are established based on the positional relationship shown in the accompanying drawings. Depending on the different accompanying drawings, the corresponding positional relationship may also change accordingly. Therefore, it cannot be understood as an absolute limitation of the protection scope.

[0048] Please refer to Figures 1 to 10 , this embodiment provides a bionic device for drug delivery, including two parts: a driving module 1 and a medicine delivery module 2. The driving module 1 and the medicine delivery module 2 are fixedly connected through a connecting piece 3. The connecting piece 3 is in the shape of a cylinder, with a diameter of 3 mm and a length of 5 mm. One end of the connecting piece 3 is fixedly connected to the bottom plate 113 of the monomer 11, and the other end of the connecting piece 3 is fixedly connected to one end of the medicine delivery capsule 21.

[0049] Specifically, the driving module 1 includes a number of monomers 11 connected in sequence. The top plate 111 of the previous monomer 11 is fixedly connected to the bottom plate 113 of the next monomer 11. A number of monomers 11 are connected in sequence to form the overall structure of the driving module 1. The axes of each monomer 11 are on the same straight line, and the monomer 11 is made of an elastic material. Each monomer 11 includes a top plate 111, a bottom plate 113, four first inclined plates 112 and four second inclined plates 114. In this embodiment, the structures and sizes of the top plate 111 and the bottom plate 113 are the same. The top plate 111 and the bottom plate 113 are both in the shape of a cuboid, and the top and bottom surfaces of the top plate 111 and the bottom plate 113 are both in the shape of a square. The outer sides of the top plate 111 are respectively fixedly connected to the first inclined plates 112, and the outer sides of the bottom plate 113 are respectively fixedly connected to the second inclined plates 114. One end of the first inclined plate 112 far from the top plate 111 is fixedly connected to one end of the second inclined plate 114 far from the bottom plate 113.

[0050] Specifically, as Figure 4As shown in the figure, when designing the driving module 1, there are many structural design parameters of the driving module 1, such as: the number of monomers 11 (i.e., the number of monomers 11), the size of the top plate 111, the size of the bottom plate 113, the projection H2 of the first inclined plate 112 along the normal direction perpendicular to the axis of the monomer 11, the width H3 of the driving module 1, the angle β between the first inclined plate 112 and the normal perpendicular to the axis of the monomer 11, the angle ɑ between the second inclined plate 114 and the normal perpendicular to the axis of the monomer 11, and the inner distance L between the top plate 111 and the bottom plate 113. In this embodiment, since the shapes of the top and bottom surfaces of the top plate 111 are both squares, the size of the top plate 111 is the side length of the square, denoted as H, and half of the size of the top plate 111 is denoted as H1. The application field of this drug delivery bionic device is the intestine. The size of the drug delivery bionic device cannot be too large, and the drug delivery bionic device has to come into contact with the intestinal wall frequently. In this embodiment, the width H3 of the driving module 1 is determined to be 20 mm. Considering the mutual influence between parameters and to avoid overdefinition of parameters, after comprehensive consideration, the following four parameters are selected as the structural design parameters when designing the driving module 1, including: the number of monomers 11, the size H of the top plate 111, the angle β between the first inclined plate 112 and the normal perpendicular to the axis of the monomer 11, and the angle ɑ between the second inclined plate 114 and the normal perpendicular to the axis of the monomer 11. And the numerical ranges of each parameter are initially determined. The range of the number of monomers 11 is 3 - 5, the range of the angle ɑ is 25 - 50°, the range of the angle β is 0 - 25°, and the range of H is 1 - 10 mm.

[0051] Specifically, the drug delivery module 2 includes a drug delivery capsule 21. The shape of the drug delivery capsule 21 is a cylinder, with a diameter of 8 - 10 mm and a length of 8 - 10 mm. One end of the drug delivery capsule 21 away from the connecting member 3 is provided with 6 - 8 uniformly distributed micropores 22. The micropores 22 are used for drug release, and the uniform distribution of the micropores 22 can avoid uneven drug release on one side. The diameter of the micropores 22 is designed to be 0.5 - 1 mm, and can be adjusted according to the viscosity of the liquid medicine and the intestinal environment during actual use. The micropores 22 are sealed with a pH-sensitive hydrogel. The hydrogel material is selected as polyacrylic acid (PAA)-based gel. The polyacrylic acid-based gel dissolves at pH ≥ 6.0, has a high swelling ratio, and a fast response speed. During use, the drug delivery capsule 21 sealed with the polyacrylic acid-based gel reaches the intestinal environment. The intestinal environment is an alkaline environment. The polyacrylic acid-based gel dissolves in the intestinal environment, and the liquid medicine in the drug delivery capsule 21 flows out from the micropores 22, thus realizing the drug release process.

[0052] Specifically, intestinal peristalsis is coordinated involuntary intestinal contraction and relaxation. The human intestinal peristalsis has about 10 radial contractions per minute, and the compression force is about 0.18 - 0.5 N / cm. This drug delivery bionic device will be affected by the intestinal peristaltic force in the intestine. The overall structure of the driving module 1 of the drug delivery bionic device is deformed. The first inclined plate 112 and the second inclined plate 114 are compressed towards the center, driving the bottom plate 113 to move forward. Since the monomer 11 is made of an elastic material, it immediately drives the top plate 111 to move forward, thus completing the entire driving process. This drug delivery bionic device uses intestinal peristalsis as the driving force, advances by deforming with the intestinal peristalsis, and realizes safe drug delivery to the intestine through its movement in the intestine. The overall structure is simple, reducing the occurrence of medical accidents.

[0053] This embodiment also provides a structural design of a drug delivery bionic device. The structural design is used to design the above drug delivery bionic device, including: determining the structural design parameters of the drug delivery bionic device. In this embodiment, there are four kinds of structural design parameters determined for the drug delivery bionic device. There will be various results for the four parameter combinations. The optimal numerical range of each parameter is obtained through the control variable method and finite element analysis, and then the optimal solution of each parameter is obtained through the orthogonal test of four factors and three levels.

[0054] Specifically, the structural design of the drug delivery bionic device includes the following steps:

[0055] S1: Select the number of monomers 11, the size H of the top plate 111, the angle β between the first inclined plate 112 and the normal line perpendicular to the axis of the monomer 11, and the angle ɑ between the second inclined plate 114 and the normal line perpendicular to the axis of the monomer 11 as the structural design parameters of the drug delivery bionic device, and then preliminarily determine the numerical range of each parameter. The range of the angle ɑ is 25 - 50°, the range of the angle β is 0 - 25°, the range of H is 1 - 10 mm, and the number of monomers 11 is 3 - 5.

[0056] S2: Conduct single-factor analysis through the control variable method, and then combine finite element analysis to obtain the single-factor analysis results, that is, the optimal numerical range of each structural design parameter. In this embodiment, the optimal numerical range of the angle ɑ takes 11°, 12°, 13°, the optimal numerical range of the angle β takes 34°, 35°, 36°, the optimal numerical range of H takes 2 mm, 3 mm, 4 mm, and the optimal numerical range of the number of monomers 11 takes 3, 4, 5.

[0057] Specifically, taking the angle ɑ as an example, the analysis process is described in detail. The specific steps are as follows:

[0058] Step 1: Fix other factors and set benchmark conditions

[0059] When studying the factor of the included angle ɑ, the values of the other three parameters are fixed. According to experience, initially select H = 3mm, β = 33°, and the number of monomers 11 is 4.

[0060] Step 2: Conduct a large-scale preliminary screening of the target factor

[0061] Analyze that the range of the factor ɑ is 0 - 25°, and set a group of tests every 5°, which are: 0°, 5°, 10°, 15°, 20°, 25°, a total of six groups of tests, covering the possible minimum and maximum values. Then conduct simulations through finite element analysis, record the test results, and draw a scatter plot of this factor and the results, as Figure 5 shown.

[0062] The specific process of conducting simulations through finite element analysis is as follows: Use solidworks software to design the intestinal model and the drug delivery bionic device model with different parameters, assemble the drug delivery bionic device model with the intestinal model, save the assembly as an X_T file, and then import it into the transient module of Ansys software. Set the material of the drug delivery bionic device as thermoplastic polyurethane (TPU) material, and add the intestinal material manually. After meshing, establish the contact settings between the intestine and the drug delivery bionic device. The two circular surfaces of the intestinal model are fixed supports, and a moving load on the outer wall of the intestine is added through the APDL command stream to simulate the peristaltic behavior of the intestine. Solve the displacement of the drug delivery bionic device in the intestine.

[0063] Step 3: Determine the key response area

[0064] Identify the extreme points in the curve. It can be seen that the parameter has the largest displacement when it is between 10 - 15°, so narrow the focus to this range.

[0065] Step 4: Precisely scan the key interval

[0066] Encrypt the test points within the key interval and repeat the tests.

[0067] Step 5: Select the level values

[0068] In principle, cover the key interval, include the optimal value, and additionally take two levels near the optimal value. That is, the included angle ɑ takes 11°, 12°, 13°.

[0069] Specifically, similarly, the included angle β takes 34°, 35°, 36°, H takes 2mm, 3mm, 4mm, and the number of monomers 11 takes 3, 4, 5. The specific analysis process of the included angle β, H, and the number of monomers 11 will not be elaborated in detail here.

[0070] S3: Design a four-factor and three-level orthogonal experiment, set up nine groups of experiments, and obtain the optimal solutions of each structural design parameter by comparing the displacement of the drug delivery bionic device. In this embodiment, the optimal solution of the included angle ɑ is 11°, the optimal solution of the included angle β is 35°, the optimal solution of H is 4 mm, and the optimal solution of the number of monomers 11 is 5.

[0071] Specifically, the specific process is as follows:

[0072] Step 1: Define the experiment purpose and determine the experiment index

[0073] For this experiment, the experiment purpose is to determine the optimal structural design parameters of the drug delivery bionic device. Therefore, the displacement of the drug delivery bionic device can be used as the experiment index to evaluate the structural design parameters of the drug delivery bionic device. The larger the displacement of the drug delivery bionic device, the better the structural design parameters of the drug delivery bionic device.

[0074] Step 2: Select factors, determine levels, and list the factor-level table

[0075] For this experiment analysis, take the size H of the top plate 111 determined in step S1, the included angle ɑ between the second inclined plate 114 and the normal line perpendicular to the axis of the monomer 11, the included angle β between the first inclined plate 112 and the normal line perpendicular to the axis of the monomer 11, and the number of monomers 11 as the experiment factors, denoted as A, B, C, D respectively, and conduct a four-factor orthogonal experiment. Each factor takes three levels, and the factor-level table is shown in Table 1.

[0076] Table 1 Factor-level table

[0077]

[0078] Step 3: Select a suitable orthogonal table

[0079] This experiment is a four-factor and three-level experiment. Since this experiment only examines the influence of four factors on the displacement, and does not consider the interaction between factors, it is advisable to select the L9(3 4 ) orthogonal table.

[0080] Step 4: Header design

[0081] Fill each factor into each column of the header in turn, and then check whether the distribution of different levels in each column is uniform. If necessary, the factor order can be randomized to reduce the experimental error.

[0082] Step 5: Compile the experiment plan, conduct the experiment according to the plan, and record the experiment results

[0083] The experiment plan is shown in Table 2.

[0084] Table 2 Experiment plan and experiment results

[0085]

[0086]

[0087] Step 6: Analysis of Test Results

[0088] (1) Determine the optimal levels and the combination of optimal levels of the test factors

[0089] Analyze the influence of each level of factor A on the test index. It can be seen from Table 3 that the influence of A1 is reflected in Tests No. 1, 2, and 3, the influence of A2 is reflected in Tests No. 4, 5, and 6, and the influence of A3 is reflected in Tests No. 7, 8, and 9.

[0090] The sum of the test indexes corresponding to level 1 of factor A is

[0091] K A1 = y1 + y2 + y3 = 1.25 + 2.29 + 2.64 = 6.18, k A1 = K A1 / 3 = 2.06;

[0092] The sum of the test indexes corresponding to level 2 of factor A is

[0093] K A2 = y4 + y5 + y6 = 6.37 + 1.66 + 2.26 = 10.29 k A1 = K A1 / 3 = 3.43;

[0094] The sum of the test indexes corresponding to level 3 of factor A is

[0095] K A3 = y7 + y8 + y9 = 4.94 + 4.37 + 2.65 = 11.96, k A1 = K A1 / 3 = 3.986667;

[0096] According to the characteristics of orthogonal design, for A1, A2, and A3, the test conditions of the three groups of tests are exactly the same (comprehensive comparability) and can be directly compared. If factor A has no influence on the test index, then k A1 , k A2 , k A3 should be equal. However, as can be seen from the above calculations, k A1 , k A2 , k A3 are actually not equal. This shows that the change in the level of factor A has an impact on the test results. Therefore, based on k A1 , k A2 , k A3The magnitudes can determine the influence degrees of A1, A2, and A3 on the test index. Since the test index is the displacement of the drug delivery bionic device, and k A3 > k A2 > k A1 , it can be determined that A3 is the optimal level of factor A.

[0097] Similarly, it can be calculated and determined that B1, C2, and D3 are the optimal levels of factors B, C, and D respectively. The optimal level combination A3B1C2D3 of the four factors is the optimal level combination of this test, that is, the optimal design parameters of the drug delivery bionic device are H = 4mm, α = 11°, β = 35°, and the number of monomers 11 is 5.

[0098] (2) Determine the primary and secondary order of factors

[0099] According to the magnitude of the range R, judge the primary and secondary influence order of factors. The larger the R, the greater the influence of the level change of this factor on the test index, and the more important the factor. The calculation results of the range R of this test are shown in Table 3, and the primary and secondary order of factor influence is DABC. That is, the number of monomers 11 has the greatest influence, followed by the size H and the included angle α of the top plate 111, while the influence of the included angle β is relatively small.

[0100] (3) Draw the trend chart of factors and indicators

[0101] Make a trend chart of factors and indicators to visually analyze the relationship between the test index and the fluctuations of each factor level. In this embodiment, the trend chart of factors and indicators is not given and will not be elaborated in detail here.

[0102] Table 3 Analysis of test results

[0103]

[0104] This embodiment also provides a preparation method of a drug delivery bionic device. The preparation method is used to prepare the above-mentioned drug delivery bionic device, including the following steps:

[0105] S1: Prepare the driving module 1: Use the fused deposition modeling (FDM) technology to prepare the driving module 1. The fused deposition modeling technology is a kind of 3D printing technology. Use TPU material. Use a direct drive extruder to reduce the extrusion problem of TPU material due to flexibility during printing. Use a printing bed with a heating function and apply glue to improve adhesion. Set the nozzle temperature to 220°, and set the printing bed temperature to 50° to improve the adhesion of the first layer. The printing speed is 15 - 30mm / s, and the retraction is turned off to avoid insufficient extrusion or blockage.

[0106] Specifically, step S1 specifically includes:

[0107] S11: Use modeling software to design the model of the driving module 1.

[0108] S12: Import the model of the drive module 1 into the slicing software, set the printing parameters in the slicing software, set the nozzle temperature to 220 °C, the printing bed temperature to 50 °C, the printing speed to 15 - 30 mm / s, the layer height to 0.2 mm, and the filling rate to 50%. After completing the parameter setting, use the slicing software to slice the model, generate a file recognizable by the printing platform, and send the file to the printing platform.

[0109] S13: Load the TPU material into the wire feeding mechanism of the printing platform, start the heating system to make the nozzle and the printing platform reach the set temperature. When the nozzle and the platform reach the set temperature, the printing platform starts to print the drive module 1.

[0110] S14: After printing is completed, turn off the printing platform. Wait for the part to cool to room temperature and then remove it. Further process the surface of the part according to the design requirements, such as polishing and grinding, to improve the surface quality and appearance effect of the part.

[0111] S2: Prepare the drug delivery module 2

[0112] S21: First, select medical-grade polycarbonate or PEEK material and process the drug delivery capsule 21 through precision injection molding. The drug delivery capsule 21 is processed in two halves, namely the upper drug delivery capsule and the lower drug delivery capsule. The inner diameter of the shell of the drug delivery capsule 21 is set to 7 mm, and the wall thickness is controlled at 0.5 mm. Then, use a laser drilling machine to evenly process six micropores 22 on the shell of the lower drug delivery capsule. The diameter of the micropores 22 is 0.5 - 1 mm. After drilling, perform plasma treatment on the inner wall of the micropores 22. The treatment parameters are oxygen atmosphere, 50 W power, and a duration of 1 minute to enhance the adhesion performance of the subsequent hydrogel.

[0113] S22: Configure a pH-sensitive hydrogel solution. Specifically: use 6% concentration of polyacrylic acid (PAA) as the matrix, add 2% concentration of polyethylene glycol diacrylate (PEGDA) as the cross-linking agent, and incorporate 0.1% concentration of photoinitiator I2959 to form a mixed solution. Magnetically stir the mixed solution for two hours until it is completely homogeneous to obtain a pH-sensitive hydrogel solution. Then store the prepared pH-sensitive hydrogel solution in the dark for later use. This formula can ensure that the gel dissolves rapidly in an environment with pH ≥ 6.5 while maintaining sufficient mechanical strength.

[0114] S23: Use the vacuum-assisted filling process to inject the liquid gel into the cavities of the upper drug delivery capsule and the lower drug delivery capsule, and ensure complete coverage of all micropores 22. Then place the upper drug delivery capsule and the lower drug delivery capsule in a vacuum chamber and maintain at -0.1 MPa negative pressure for 5 minutes to remove air bubbles. Immediately perform ultraviolet curing treatment after taking them out. Use a 365 nm wavelength ultraviolet light source with an intensity of 10 mW / cm2 , irradiate for 10 minutes to completely crosslink the gel. After curing, remove the excess gel on the surface with a precision spatula and wash the residue with ethanol.

[0115] S24: In a clean environment, use a micro syringe to inject the drug into the lower drug delivery capsule cavity. After precisely aligning the upper drug delivery capsule with the lower drug delivery capsule, perform laser welding for sealing. The welding parameters are set as a power of 20 W and a pulse frequency of 1 kHz, and the sealing is completed under argon protection. After encapsulation, conduct an airtightness test by immersing the device in a dyed PBS solution under a pressure of 50 kPa to detect leakage.

[0116] S25: After completion, perform ethylene oxide sterilization on the drug delivery capsule 21. The sterilization conditions are a temperature of 55 °C, a humidity of 60%, and a sterilization time of 4 hours. After sterilization, perform primary packaging in a sterile environment, seal it with an aluminum-plastic composite film, and label the key parameters including the gel response pH value, sterilization date, and expiration date. The finished product needs to be stored in a cool and dry place, avoiding direct sunlight.

[0117] S3: Assemble the drive module 1 and the drug delivery module 2.

[0118] The above embodiments only illustrate the basic principles and characteristics of the present invention, but are not limited by the above embodiments. It should be understood that for those of ordinary skill in the art, various changes and modifications can be made to the present invention without departing from the spirit and scope of the present invention, and these changes and modifications all fall within the scope of the present invention claimed. The scope of the present invention claimed is defined by the appended claims and their equivalents.

Claims

1. A drug delivery bionic device, characterized in that, It includes a driving module (1) and a drug delivery module (2). The drug delivery module (2) is fixedly connected to the driving module (1). The driving module (1) includes a number of monomers (11) connected in sequence. The monomers (11) are made of elastic materials. The monomer (11) includes a top plate (111), a bottom plate (113), a first inclined plate (112) and a second inclined plate (114). The outer side of the top plate (111) is fixedly connected to a number of first inclined plates (112). The outer side of the bottom plate (113) is fixedly connected to a number of second inclined plates (114). One end of the first inclined plate (112) far from the top plate (111) is fixedly connected to one end of the second inclined plate (114) far from the bottom plate (113).

2. The drug delivery bionic device according to claim 1, characterized in that, The drug delivery module (2) includes a drug delivery capsule (21). A number of micropores (22) for releasing drugs are provided at one end of the drug delivery capsule (21) far from the driving module (1).

3. The bionic drug delivery device according to claim 2, wherein The diameter of the micropores (22) is 0.5 - 1 mm.

4. The drug delivery bionic device according to claim 1, wherein, The structural design parameters of the driving module (1) include: the number of monomers (11), the size of the top plate (111), the angle β between the first inclined plate (112) and the normal line perpendicular to the axis of the monomer (11), and the angle ɑ between the second inclined plate (114) and the normal line perpendicular to the axis of the monomer (11).

5. The bionic drug delivery device according to claim 4, characterized in that, The shapes of the top surface and the bottom surface of the top plate (111) are both square. The size of the top plate (111) is the side length H of the square. The range of the side length H is 1 - 10 mm. The range of the number of monomers (11) is 3 - 5. The range of the angle ɑ is 25 - 50°. The range of the angle β is 0 - 25°.

6. The structural design of a drug delivery bionic device as described in any one of claims 1-5, characterized in that, Determine the structural design parameters of the drug delivery bionic device. Obtain the optimal numerical range of each parameter through the control variable method and finite element analysis, and then obtain the optimal solution of each parameter through the orthogonal test of four factors and three levels.

7. The structural design of the drug delivery bionic device according to claim 6, characterized in that, It includes the following steps: S1: Select the number of monomers (11), the size of the top plate (111), the angle β between the first inclined plate (112) and the normal line perpendicular to the axis of the monomer (11), and the angle ɑ between the second inclined plate (114) and the normal line perpendicular to the axis of the monomer (11) as the structural design parameters of the drug delivery bionic device, and then determine the numerical range of each parameter; S2: Conduct single - factor analysis through the control variable method, and then combine finite element analysis to obtain the single - factor analysis results, that is, the optimal numerical range of each structural design parameter; S3: Design an orthogonal test of four factors and three levels, set nine groups of experiments, and obtain the optimal solution of each structural design parameter by comparing the displacement of the drug delivery bionic device.

8. A method for preparing a drug delivery bionic device according to any one of claims 1-5, characterized in that, It includes the following steps: S1: Prepare the driving module (1): Use 3D printing technology to prepare the driving module (1); S2: Prepare the drug delivery module (2) S21: Process the drug delivery capsule (21), then process the micropores (22) on the drug delivery capsule (21), and perform plasma treatment on the inner wall of the micropores (22) after processing; S22: Configure a pH - sensitive hydrogel solution; S23: Inject the hydrogel solution into the cavity of the drug delivery capsule (21), then place the drug delivery capsule (21) in a vacuum chamber to remove air bubbles, and then perform ultraviolet curing treatment. After the treatment, remove the excess gel and residues; S24: Inject the drug into the cavity of the drug delivery capsule (21), then seal the drug delivery capsule (21). After sealing, perform an airtightness test; S25: After completion, perform sterilization treatment on the drug delivery capsule (21). After the treatment, perform packaging in a sterile environment; S3: Assemble the drive module (1) and the drug delivery module (2).

9. The preparation method of the drug delivery bionic device according to claim 8, characterized in that, The specific steps of step S1 include: S11: Use modeling software to design the model of the drive module (1); S12: Import the model of the drive module (1) into the slicing software, set the printing parameters in the slicing software. After completing the parameter setting, use the slicing software to slice the model to generate a file recognized by the printing platform, and send the file to the printing platform; S13: The printing platform prints the drive module (1); S14: After printing, turn off the printing platform. Wait for the part to cool to room temperature and then remove it. Treat the surface of the part according to the design requirements.

10. The preparation method of the drug delivery bionic device according to claim 8, wherein, The specific steps of step S22 include: Use polyacrylic acid with a concentration of 6% as the matrix, add polyethylene glycol diacrylate with a concentration of 2% as the crosslinking agent, and incorporate a photoinitiator with a concentration of 0.1% to form a mixed solution. Stir the mixed solution until it is uniform to obtain a pH-sensitive hydrogel solution.

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