Absorbable coronary stent based on 3D printing and preparation method thereof

Abstract

The invention discloses an absorbable coronary stent based on 3D printing and a preparation method of the absorbable coronary stent. The absorbable coronary stent comprises a plurality of annular units and connecting units, wherein the annular units are sequentially arranged in the axial direction, and the connecting units are used for connecting the adjacent annular units; the annular unit is a closed-loop annular base body, functional partition is conducted on the annular unit in the axial direction, and the annular unit specifically comprises a first unit used for providing radial supporting force and arranged in a calcification area; the second unit is used for realizing a drug release function and is arranged in the long lesion area; and the third unit is used for providing rigid-flexible transition and stress buffering and is arranged in the large bending area. Through collaborative partitioning of the structure, materials and functions, the contradiction between radial supporting force and flexibility of a traditional stent is solved, local stress concentration after the stent is implanted is effectively reduced, long-term compatibility of the stent to blood vessels is improved, and precise sequential release of drugs is achieved.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of medical instrument equipment, and relates to an absorbable coronary stent based on 3D printing and a preparation method thereof. BACKGROUND

[0002] Vascular stenosis caused by coronary atherosclerosis is one of the most common cardiovascular diseases in clinical, and percutaneous coronary intervention has become the main treatment method, which expands the stenotic blood vessels by a balloon and implants a coronary stent to maintain the long-term patency of the blood vessel lumen. The existing coronary stents mainly include a metal bare stent, a drug-eluting stent and a degradable stent. The metal bare stent can provide a relatively high radial support force, but permanent implantation in the body can cause delayed thrombosis and a decrease in vascular compliance; the drug-eluting stent can reduce the risk of restenosis by coating a drug polymer layer on the surface of the stent, but the coating is prone to cracking or peeling during expansion and delivery; the degradable stent gradually degrades over time, which can reduce the long-term foreign body reaction and is the focus of research in recent years.

[0003] The patent document with the publication number CN120501567A discloses a coronary stent with a long gradual change structure, which is prepared by traditional processing methods such as laser cutting. However, such processes can only process two-dimensional unfolded structures with a single wall thickness and a single material, and it is difficult to build small drug cavities inside the stent or achieve integrated forming of multiple materials and multiple levels, thereby limiting the optimization of drug dosage, drug release mode and structure function partition. In addition, the stent system needs to pass through the peripheral blood vessels to reach the target lesion site during delivery, and the smaller the compressed outer diameter, the more conducive to the passability in the tortuous and stenotic blood vessels and the reduction of the risk of blood vessel damage; but the reduction of the compressed outer diameter often leads to a decrease in stent adhesion and insufficient fixation, and if the support force is increased by thickening the rod or increasing the structural coverage, stress concentration, decreased flexibility and insufficient fatigue safety will be introduced. The support force distribution of the stent obtained by traditional processing is often fixed, and it is difficult to flexibly adjust the structure between high stress areas and non-bearing areas to balance the support strength and flexibility.

[0004] The patent document with the publication number CN120105607A discloses a degradable coronary stent with a negative Poisson's ratio structure, which is a tubular object composed of a representative structural unit of an inner concave hexagon. Each of the inner concave hexagons includes two parallel and equal-length straight sides, and two groups of oblique sides extending inward from the same side endpoints of the straight sides by the same angle and length. However, these existing coronary stents generally have the technical problems of the contradiction between the compressed outer diameter and the radial support force after expansion, the inability to achieve stress uniformization of the stent after expansion, and the difficulty in constructing a multi-material, multi-level structure and an internal drug cavity. SUMMARY

[0005] In order to overcome the above-mentioned defects of the prior art coronary stents, the inventors conceive and make a 3D printing-based absorbable coronary stent and a preparation method thereof, which solve the technical problems of the contradictory between the compressed outer diameter and the radial support force after expansion of the traditional stent, the inability to realize stress homogenization of the stent after expansion, and the difficulty in constructing a multi-material, multi-level structure and an internal drug cavity. Specifically, the present application comprises the following technical solutions.

[0006] In one aspect, the present application provides a 3D printing-based absorbable coronary stent, which comprises a plurality of ring units arranged in sequence along the axial direction and a connecting unit connecting adjacent ring units; the ring unit is a closed ring-shaped base, and the ring unit is functionally partitioned along the axial direction, specifically comprising: a first unit for providing radial support force, arranged in the calcification area; a second unit for realizing drug release function, arranged in the long lesion area; a third unit for providing rigid-flexible transition and stress buffering, arranged in the large bending area.

[0007] Further, the ring-shaped base of the ring unit is configured in a wave structure, such as a honeycomb structure, a continuous Z shape or a wave shape, which comprises a plurality of connecting parts and corner parts connecting adjacent two connecting parts, and the connecting parts are sequentially connected head to tail to form a closed ring-shaped base, and the connecting parts are connected with the connecting unit.

[0008] In an optional embodiment, the connecting unit is formed by assembly with the ring-shaped base, a groove is formed on the connecting part, the end of the connecting unit is provided with a protrusion matched with the groove, and the groove and the protrusion form a mortise and tenon joint.

[0009] Further, the extension direction of the groove and the extension direction of the protrusion are arranged at an angle, such as perpendicular.

[0010] Preferably, the second unit is divided into a bearing area and a drug-loaded area; the bearing area is located at the corner part, the drug-loaded area is located at the connecting part, and the stress of the drug-loaded area is lower than that of the bearing area.

[0011] Preferably, the drug-loaded area of the second unit is provided with a drug cavity extending along the axial direction, the drug cavity is filled with a drug, and the opening of the drug cavity is sealed and covered with a first degradation protection layer.

[0012] Further, the drug cavity is a micron-level channel or an array-type cavity extending along the axial direction of the drug-loaded area of the second unit, and 2-6 of which can be uniformly arranged around the circumference of the second unit.

[0013] Further, the first degradation protection layer is provided with a release channel on the side facing the blood vessel wall, and the release channel is a release micropore or a release microslit to realize directional release of the drug.

[0014] Preferably, the third unit is internally integrated with a fluid cavity, the fluid cavity is a permanently sealed structure, and the fluid cavity is filled with a bioabsorbable shear thickening composite fluid.

[0015] It should be noted that the cross section of the microfluidic cavity is a flat non-circular structure, such as an elliptical or rectangular structure, which ensures the fluid volume.

[0016] Preferably, the outer side of the third unit is integrated with a degradable barb or microspine.

[0017] Preferably, the outer surface of the first unit, the second unit and the third unit is coated with a second degradation protection layer as a whole, and the degradation time of the second degradation protection layer is shorter than that of the first degradation protection layer.

[0018] Another aspect of the present application also provides a preparation method of the absorbable coronary stent described above, comprising the following steps:

[0019] S1: obtaining the target vessel diameter and lesion length, and establishing a three-dimensional model of the first unit, the second unit, the third unit and the connecting unit;

[0020] S2: arranging degradable raw materials in the 3D printing device, and printing the first unit, the second unit, the third unit and the connecting unit, and switching to the required preparation material when starting to the position corresponding to the drug loading area of the first unit and the third unit;

[0021] S3: coating the surface of the first unit, the second unit and the third unit with a second degradation protection layer as a whole;

[0022] S4: warm control and pressure holding loading to the balloon under the condition of 20℃-40℃.

[0023] The 3D printing based absorbable coronary stent and the preparation method thereof have the following beneficial effects:

[0024] 1. The present application divides the ring unit into functional zones along the axial direction, including the first unit for providing radial support force (arranged in the calcified area), the second unit for realizing drug release function (arranged in the long lesion area), and the third unit for providing rigid-flexible transition and stress buffering (arranged in the large bending area). The problem that the mechanical properties and biological functions cannot be considered together caused by the "one-size-fits-all" of traditional stents is solved. In addition, each unit is made by multi-material 3D printing technology, realizing the customization of materials and structure, and being able to arrange according to the actual lesion condition (such as calcified area, large bending area, long lesion area), providing more accurate treatment scheme.

[0025] 2、The first unit improves the structural stability and wall adhesion of the stent after expansion, provides strong support similar to a metal stent, and prevents retraction. At the same time, the third unit is internally integrated with a fluid cavity filled with a biocompatible shear thickening composite fluid, which has non-Newtonian fluid properties and can instantaneously increase viscosity under external pulsatile pressure, achieving passive adaptive adjustment of stent stiffness and stress buffering function, effectively reducing local stress concentration, avoiding "stent straightening effect" caused by blood vessel injury or "dog bone effect", and improving the long-term compatibility of the stent with the blood vessel.

[0026] 3、The stent realizes drug arrangement and time release while bearing through the second unit. The drug loading area of the second unit is provided with a drug cavity extending in the axial direction, the drug cavity is filled with a drug, and is sealed and covered by a first degradation protection layer. This design completely avoids the cracking and peeling problem of traditional drug coating during expansion or transportation, making the drug release curve more stable and controllable.

[0027] 4、The first degradation protection layer can be provided with a release channel (such as a micropore or a microslit) towards the blood vessel wall side, realizing directional release of the drug and improving the local drug concentration. At the same time, the outer surface of the stent is coated with a second degradation protection layer, which has a shorter degradation time than the first degradation protection layer, to provide early postoperative anti-thrombus and anti-inflammatory protection, making the overall release curve smooth. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 is a structural schematic diagram of an absorbable coronary stent embodiment based on 3D printing.

[0029] Figure 2 is a structural schematic diagram of a single ring-shaped unit in an absorbable coronary stent based on 3D printing.

[0030] Figure 3 is a sectional plane structural schematic diagram of a drug cavity in an absorbable coronary stent based on 3D printing.

[0031] Figure 4 is a sectional plane structural schematic diagram of a fluid cavity in an absorbable coronary stent based on 3D printing.

[0032] Figure 5 is a flowchart of a preparation method of an absorbable coronary stent based on 3D printing. DETAILED DESCRIPTION

[0033] Embodiment One

[0034] The absorbable coronary stent based on 3D printing provided in this embodiment, as shown in Figure 1 , has a main body in a net tube structure, including a plurality of groups of ring-shaped units arranged in sequence along the axial direction and a connecting unit 2 connecting adjacent two ring-shaped units.

[0035] Specifically, as shown in Figure 2 The annular base body is in a wave structure, which can be but is not limited to a honeycomb structure, a continuous Z shape or a wave shape. The annular base body is provided with a plurality of connecting portions 101 for connecting with the connecting units 2, two adjacent connecting portions 101 are connected through a corner portion 102, and a plurality of connecting portions 101 are sequentially connected with a plurality of connecting portions 101 at the head and tail to form a closed annular base body.

[0036] The annular base body can be made of but is not limited to a degradable polymer material or a degradable metal.

[0037] Preferably, the degradable polymer material is at least one selected from lactic acid, polyglycolide, polyanhydride, polylactic acid copolymer, polyglycolic acid, polyhydroxybutyrate valerate, polycyanoacrylate, natural degradable polymer material collagen, gelatin, chitin, rapamycin, paclitaxel, emodin and curcumin.

[0038] Preferably, the degradable metal is magnesium, iron or zinc.

[0039] Specifically, the connecting units 2 and the annular base body are integrally formed or assembled by multi-material 3D printing technology.

[0040] When the connecting units 2 and the annular base body are assembled, the annular base body and the connecting units 2 are separately printed and fixedly connected as a whole by subsequent installation and cooperation. The preparation can be performed in the following manner:

[0041] In an alternative embodiment, a recess is formed on the connecting portion 101 of the annular base body, which can be but is not limited to a rectangular, dovetail or semicircular structure. The end of the connecting unit 2 is provided with a protrusion matched with the recess in a mortise and tenon manner. The extension direction of the recess and the extension direction of the protrusion are at a certain angle. In this embodiment, the extension direction of the recess and the extension direction of the protrusion are perpendicular. The integrally formed or high-precision assembled by 3D printing can prevent the connecting unit 2 from being separated by using the mechanical interlocking principle when it is subjected to axial stretching or compression, thereby solving the problem of weak interfacial bonding force of multi-materials.

[0042] In another alternative embodiment, the connecting portion 101 of the annular base body is provided with an insertion port, and the connecting unit 2 is an elongated strip-shaped bridging piece which is arranged in an array along the radial direction of the annular base body, and the two ends thereof are respectively inserted and fixedly connected with the insertion ports on the connecting portion 101.

[0043] In order to balance the radial support force, drug release function and the compliance to the blood vessel of the stent, the annular unit is designed by functional partitioning, which solves the problem that the mechanical properties and biological functions cannot be balanced due to the "one-size-fits-all" of the traditional stent. As shown in Figure 1As shown, specifically includes a first unit 11, a second unit 12 and a third unit 13, the first unit 11, the second unit 12 and the third unit 13 coaxial arrangement.

[0044] It should be noted that the first unit 11 is used to realize the main bearing function of the stent, improve the structural stability and wall adhesion of the stent after expansion; the second unit 12 is used to realize the arrangement of the drug and the time sequence release of the drug while bearing, the third unit 13 is used to realize the passive self-adaptive adjustment of the stent stiffness and the stress buffer function while bearing, effectively reducing the local stress concentration and improving the long-term compatibility of the stent to the blood vessel; the connecting unit 2 is used to realize the connection of the first unit 11, the second unit 12 and the third unit 13.

[0045] Among them, the first unit 11 is printed by the material with the maximum stress and the slowest degradation speed, providing the main radial support force after expansion, arranging the first unit 11 in the calcified area to provide strong support similar to the metal stent to prevent retraction; arranging the second unit 12 in the long lesion area to release the anti-proliferative drug and accurately inhibit the intimal hyperplasia, the second unit 12 is provided with a bearing area and a drug loading area, the bearing area guarantees the stress support, and the drug loading area provides the stage release of the drug to realize the time sequence drug release; arranging the third unit 13 in the large bending area, using the flexibility of the non-Newtonian fluid to avoid the blood vessel injury caused by the "stent straightening effect", the third unit is provided with a fluid cavity 131, and the fluid cavity 131 is provided with a biodegradable shear thickening composite fluid (similar to a non-Newtonian fluid) inside, having a stress buffer function to realize stress self-adaptation.

[0046] Preferably, the preparation material of the first unit 11 and the connecting unit 2 can be but is not limited to polylactic acid PLLA, the preparation material of the second unit 12 can be but is not limited to polylactic acid PLLA and polylactic acid-glycolic acid copolymer PLGA, and the preparation material of the third unit 13 can be but is not limited to polylactic acid-glycolic acid copolymer PLGA.

[0047] As shown in Figure 3 The connecting part 101 and the corner part 102 in the second unit 12 are respectively the drug loading area and the bearing area, and the stress of the drug loading area is lower than that of the bearing area, the drug loading area of the second unit 12 is provided with a drug cavity 121, and the drug cavity 121 is provided with a drug, which can be a common coating drug on the stent, such as selected from P(LA-TMC)+sirolimus, PLGA+paclitaxel and PLLA+sirolimus, etc., and the outside opening of the drug cavity 121 is sealed and covered with a first degradation protection layer 122, and the first degradation protection layer 122 can adjust the degradation speed of the drug.

[0048] Further, the drug cavity 121 is a micron-sized channel or an arrayed cavity extending along the drug-loading area of the second unit 12, and 2-6 of which can be uniformly arranged around the circumference of the second unit 12.

[0049] In an optional embodiment, as shown in Figure 3 The first degradation protection layer 122 is provided with a micron-sized or nanometer-sized release channel 123 on the side facing the blood vessel wall, and the release channel 123 is a release micropore or a release microslit to realize directional release of the drug and improve the local drug concentration.

[0050] The design of the drug cavity 121 completely avoids the problem of coating cracking and peeling, and the arrangement of the drug cavity 121 makes the drug release curve more stable and controllable and safer.

[0051] It should be noted that the first degradation protection layer 122 is formed by 3D printing equipment using polylactic acid-glycolic acid copolymer PLGA or polycaprolactone PCL material. The first degradation protection layer 122, the bearing area and the drug-loading area are integrally formed by using a multi-material multi-nozzle 3D printing equipment during 3D printing.

[0052] The third unit 13 is used as a rigid-flexible transition area to improve the compliance of the stent to the blood vessel bending. As shown in Figure 4 The third unit 13 is internally provided with a fluid cavity 131, and the fluid cavity 131 is a permanently sealed structure. The fluid cavity 131 is provided with a bioabsorbable shear thickening composite fluid, and the shear thickening composite fluid has the characteristics of a non-Newtonian fluid. Under the action of external pulsatile pressure, the viscosity of the shear thickening composite fluid instantaneously increases, providing passive adaptive stiffness compensation, and effectively reducing the risk of dog bone effect.

[0053] The third unit 13 utilizes the non-Newtonian fluid characteristics of the shear thickening composite fluid to achieve "rigid-flexible combination": in a normal state, the fluid is soft, which gives the stent end excellent compliance and avoids the cutting of the stent edge to the blood vessel wall (i.e., "dog bone effect"); when subjected to external pulsatile pressure impact or blood vessel spasm (high shear rate), the shear thickening composite fluid instantaneously becomes viscous and hard, providing stiffness compensation and stress buffering.

[0054] Preferably, as shown in Figure 4 The cross section of the microfluid cavity 131 is a flat non-circular structure, such as an elliptical or rectangular structure, to minimize the impact on the stent pressure diameter under the premise of ensuring the fluid volume.

[0055] Further, the outer side of the third unit 13 is integrated with micron-sized barbs or microspikes (not shown in the figure) to provide longitudinal fixation in the early stage and prevent displacement of the stent after implantation.

[0056] The outer surfaces of the first unit 11, the second unit 12 and the third unit 13 are coated with a second degradation protection layer (not shown in the figure) as a whole, and the thickness is set to 1-4 microns. The degradation time of the second degradation protection layer is shorter than that of the first degradation protection layer 122, thereby providing early postoperative anti-thrombus and anti-inflammatory protection and smoothing the overall release curve.

[0057] Regardless of laser cutting or conventional 3D printing, once the stent is formed, the overall mechanical properties (such as radial support force, flexibility) and drug release capacity of the stent are uniformly distributed throughout the length. Doctors can only choose compromises, such as choosing a stent that is too hard overall in order to support the calcified area, resulting in damage to the blood vessel in the tortuous area. In the present embodiment, the arrangement can be adjusted according to the actual situation, such as arranging more first units 11 in the calcified area to provide strong support similar to a metal stent to prevent retraction, arranging more third units 13 in the large curved area to avoid blood vessel injury caused by the "stent straightening effect" by using the flexibility of non-Newtonian fluid, and arranging second units 12 in the long lesion area to release anti-proliferative drugs and precisely inhibit intimal hyperplasia.

[0058] The present application solves the contradictory relationship between the radial support force and flexibility of the conventional stent through the synergistic division of structure, material and function, effectively reduces the local stress concentration after stent implantation, improves the long-term compatibility of the stent with the blood vessel, and realizes the precise time release of the drug.

[0059] Embodiment Two

[0060] The present embodiment provides a preparation method of the absorbable coronary stent as described in Embodiment One, as shown in the figure, the preparation process comprises the following steps: Figures 1 to 4

[0061] S1: Obtain the target blood vessel diameter and lesion length, establish a three-dimensional model of the size-adapted first unit 11, second unit 12, third unit 13 and connecting unit, determine the specific position, number and size of the drug cavity 121 in the second unit 12, determine the position, number and size of the fluid cavity 131 in the third unit 13, and determine the preparation material of the first unit 11, the second unit 12 and the third unit 13;

[0062] S2: Arrange degradable polymer materials or degradable metals in the 3D printing equipment, and print the first unit 11, the second unit 12 and the third unit 13. The printing equipment reciprocates from one end to the other end. A multi-material 3D printing equipment can be used. An FDM series printing equipment can be used. When starting to the position corresponding to the drug loading area of the first unit 11 and the third unit 13, switch to the required preparation material;

[0063] ​First, the first unit 11 annular base and the connecting part groove at the corner thereof are printed layer by layer on the 3D printing device, and then the multi-nozzle mode is switched to print the bearing area with PLLA, the drug loading area with PLGA or polycaprolactone PCL, and the drug cavity part, the step / tooth-shaped locking structure and the insertion port are integrally formed, so as to complete the material and structure cooperative partitioning on the same construction platform. The first degradation protection layer is directly printed at the drug cavity opening with PLGA or polycaprolactone PCL, the layer thickness is controlled to be 5-30 μm, and the micropore / microslit array can be formed according to the requirement, the connecting unit 2 is printed with PLLA, the tongue protrusion and the stop tooth are formed,

[0064] The third unit 13 is printed with polycaprolactone PCL, the perfusion port is reserved outside the fluid cavity 131 of the third unit 13, the shear thickening composite fluid is filled into the fluid cavity 131 by micro-injection, and the perfusion port is sealed by directional light curing / micro-laser welding. The tongue of the connecting unit 2 is radially inserted through the insertion port of each annular base. In some embodiments, directional light curing or laser melting can be used to integrally form the connecting unit 2 and the connecting part 10;

[0065] S3: The outer surface of the first unit 11, the second unit 12 and the third unit 13 is coated with a second degradation protection layer as a whole, which can be completed by spraying, dipping or spin coating, but is not limited to these methods. The second degradation protection layer has a thickness of 1 μm-4 μm, so as to provide early postoperative anti-thrombus and anti-inflammatory protection, and to make the overall release curve smooth;

[0066] S4: The stent is loaded into the balloon under temperature control and pressure at 20℃-40℃.

[0067] The above describes the 3D printing based absorbable coronary stent and the preparation method thereof in detail. The above embodiments are only used to help understand the inventive concept of the present application. Those skilled in the art should understand that the present application is not limited to the above embodiments, and the above embodiments and the description in the specification are only the principles of the present application. Without departing from the spirit and scope of the present application, various changes and improvements can be made to the present application, and these changes and improvements all fall within the scope of the claimed present application. The protection scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A 3D printing based absorbable coronary stent, characterized in that: The device comprises a plurality of ring units arranged in sequence along the axial direction and connecting units (2) connecting adjacent ring units; the ring unit is a closed ring base, and the ring unit is functionally divided along the axial direction, comprising: a first unit (11) for providing radial support force, arranged in the calcification area; a second unit (12) for realizing drug release function, arranged in the long lesion area; a third unit (13) for providing rigid-flexible transition and stress buffering, arranged in the large bending area.

2. The 3D printing-based absorbable coronary stent according to claim 1, characterized in that: the ring base of the ring unit is configured as a wave structure, comprising a plurality of connecting portions (101) and corner portions (102) connecting adjacent two connecting portions (101), and the connecting portion (101) is connected with the connecting unit (2).

3. The 3D printing-based absorbable coronary stent according to claim 2, characterized in that: a groove is formed on the connecting portion (101), and the end of the connecting unit (2) is provided with a protrusion matched with the groove, and the groove and the protrusion form a mortise and tenon joint; the extension direction of the groove and the extension direction of the protrusion are arranged at an angle.

4. The 3D printing-based absorbable coronary stent according to claim 2, characterized in that: the second unit (12) is divided into a bearing area and a drug loading area; the bearing area is located at the corner portion (102), the drug loading area is located at the connecting portion (101), and the stress of the drug loading area is lower than that of the bearing area.

5. The 3D printing-based absorbable coronary stent according to claim 4, characterized in that: the drug loading area of the second unit (12) is provided with a drug cavity (121) extending along the axial direction, the drug cavity (121) is filled with a drug, and the opening of the drug cavity (121) is sealed and covered with a first degradation protection layer (122).

6. The 3D printing-based absorbable coronary stent according to claim 5, characterized in that: the first degradation protection layer (122) is provided with a release channel (123) on the side facing the blood vessel wall, and the release channel (123) is a release micropore or a release microslit to realize directional release of the drug.

7. The 3D printing-based absorbable coronary stent according to claim 1, characterized in that: the third unit (13) is integrated with a fluid cavity (131) inside, the fluid cavity (131) is a permanent sealing structure, and the fluid cavity (131) is filled with a biocompatible shear thickening composite fluid.

8. The 3D printing-based absorbable coronary stent according to claim 7, characterized in that: the outer side of the third unit (13) is integrated with a degradable barb or microspike.

9. The 3D printing based absorbable coronary stent according to claim 5, wherein: The outer surfaces of the first unit (11), the second unit (12) and the third unit (13) are coated with a second degradation protection layer, and the degradation time of the second degradation protection layer is shorter than that of the first degradation protection layer (122).

10. A method for preparing an absorbable coronary stent according to claim 9, characterized in that: The method comprises the following steps: S1: Obtain the target blood vessel diameter and lesion length, and establish a three-dimensional model of the first unit (11), the second unit (12), the third unit (13), and the connecting unit (2); S2: In the 3D printing device, the device can degrade the raw material, and print the first unit (11), the second unit (12), the third unit (13), and the connecting unit (2). When starting to the position corresponding to the drug loading area of the first unit (11) and the third unit (13), switch to the required preparation material; S3: The surface of the first unit (11), the second unit (12), and the third unit (13) is coated with a second degradation protection layer; S4: Perform temperature control and pressure holding loading to the balloon under the condition of 20℃-40℃.

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