CN112870435A

CN112870435A - rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material and preparation method thereof

Info

Publication number: CN112870435A
Application number: CN202011640044.2A
Authority: CN
Inventors: 杜昶; 戴欣; 郑志雯; 李雪杨
Original assignee: South China University of Technology SCUT
Current assignee: South China University of Technology SCUT
Priority date: 2020-12-31
Filing date: 2020-12-31
Publication date: 2021-06-01

Abstract

The invention discloses a small-caliber intravascular stent material modified by rH-PLGA/PEI microspheres and dopamine and a preparation method thereof. The method comprises the following steps: the PCL nano-fiber scaffold prepared by the electrostatic spinning technology is used as a substrate, a layer of dopamine is deposited on the surface of the PCL nano-fiber scaffold, and PLGA/PEI microspheres wrapping hirudin are loaded on the PCL nano-fiber by utilizing the adhesion of the dopamine to obtain the small-caliber intravascular scaffold material. The method combines hirudin, PLGA/PEI microspheres and dopamine to obtain the stent which can prevent thrombus for a long time and promote rapid endothelialization and angiogenesis, and has simple and feasible process and good repeatability. The small-caliber blood vessel stent has good biocompatibility, and the speed and the quality of vascular tissue repair are accelerated by utilizing the promotion effect and the anticoagulation property of hirudin on endothelial cell adhesion and proliferation.

Description

rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material and preparation method thereof

Technical Field

The invention belongs to the field of degradable vascular stents, and particularly relates to a small-caliber vascular stent material modified by rH-PLGA/PEI microspheres and dopamine and a preparation method thereof.

Background

With the improvement of living standard, the aging of social population becomes a trend, and the main cause of death of aging population is cardiovascular disease. In addition to drug therapy, stent intervention surgery and vascular grafting have become the main means of arteriosclerosis treatment.

At present, large blood vessel replacement has achieved better curative effect in clinic, but transplantation of small-caliber blood vessels still has the problems of low long-term patency rate, secondary operation and the like. Therefore, the preparation of the synthetic material with good biocompatibility, the requirement on the properties of blood vessels, the prevention of thrombosis and the improvement of long-term patency rate is an effective method for solving the problem of small-caliber blood vessel transplantation. The ideal blood vessel transplant has the characteristics of meeting the requirement of blood vessel mechanics, good biocompatibility, good antithrombotic and patency rate after transplantation, safety, no toxicity, no immunological rejection, simple and easy preparation method, low cost and the like.

Hirudin and thrombin are irreversibly bound in a 1:1 molar ratio to form a non-covalent complex, thereby preventing a thrombin-mediated coagulation reaction.

Wanjianan et al provide a method for preparing an anticoagulant material, comprising the steps of: s1) mixing the silk fibroin solution, polyethylene glycol diamine and a cross-linking agent, and reacting to obtain a polyethylene glycol diamine cationized silk fibroin material; soaking the polyethylene glycol cationized silk fibroin material in water to obtain a soaked cationized silk fibroin material, and soaking the soaked cationized silk fibroin material in a hirudin solution to obtain the anticoagulant material. Although the preparation method protects the functional group of the thrombin binding region from being reacted to influence the thrombin binding domain, and enables hirudin to be bound to the polyethylene glycol diamine cationized silk fibroin through strong binding force ionic bonds, the obtained anticoagulant material has the function of obviously inhibiting the thrombin activity, but can not provide continuous anticoagulation.

Disclosure of Invention

In order to overcome the defects in the prior art, the invention aims to provide an rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material and a preparation method thereof.

The invention aims to provide a hirudin and dopamine loaded tissue engineering nanofiber scaffold, and aims to realize the aims of sustainable anticoagulation and rapid endothelialization promotion on the basis of meeting the requirements of a common tissue engineering nanofiber scaffold and promote the repair of vascular tissues.

The purpose of the invention is realized by at least one of the following technical solutions.

In order to protect the active sites at the C end and the N end of hirudin, the preparation method provided by the invention firstly prepares rH-PLGA-PEI microspheres, then uses dopamine as an intermediate layer to load the rH-PLGA-PEI microspheres on PCL nano-fibers, and finally constructs a PCL nano-fiber scaffold which can continuously target the anticoagulation of thrombin, resist stain and rapidly promote endothelialization. The PLGA/PEI coated hirudin can realize the sustained release of the hirudin and the long-term anticoagulation of the PCL nanofiber scaffold.

The invention provides an rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material which is composed of polycaprolactone, PLGA/PEI microsphere wrapping hirudin and dopamine. The PCL nanofiber scaffold is prepared by an electrostatic spinning technology, and PLGA/PEI microspheres wrapping hirudin are further loaded by depositing dopamine. The dopamine can greatly improve the hydrophilicity of the PCL and can also provide adhesion for the loading of PLGA/PEI microspheres wrapping hirudin. The PLGA/PEI microsphere coated with hirudin can realize long-time slow release of hirudin, long-time anticoagulation and prevention of thrombosis.

The invention provides a preparation method of a small-caliber intravascular stent material modified by rH-PLGA/PEI microspheres and dopamine, which comprises the following steps:

(1) adding Polycaprolactone (PCL) into hexafluoroisopropanol, uniformly stirring (the stirring time is preferably 24h) to obtain a spinning solution, and preparing the PCL nanofiber scaffold by using an electrostatic spinning technology; soaking the PCL nano fiber scaffold in a dopamine solution for standing and light-shielding treatment, taking out, washing for 3 times with distilled water, and drying to obtain a PDA-PCL nano fiber scaffold;

(2) mixing hirudin solution with PLGA solution, and homogenizing with a homogenizer to obtain colostrum (W)₁O); then pouring the primary emulsion into PVA solution, adding polyetherimide, and performing secondary homogenization treatment by a homogenizer to obtain multiple emulsion (W)₁/O/W₂)；

(3) Dripping the multiple emulsion obtained in the step (2) into a PVA solution, adding polyethyleneimine, stirring, centrifugally washing with distilled water, and freeze-drying to obtain rH-PLGA-PEI microspheres; adding the rH-PLGA-PEI microspheres into water, and uniformly mixing to obtain a suspension;

(4) loading rH-PLGA-PEI microspheres on the PDA-PCL nano fiber scaffold: and (3) soaking the PDA-PCL nanofiber scaffold in the step (1) in the suspension in the step (3), stirring, taking out the scaffold, washing with distilled water, and drying to obtain the rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material.

Further, the mass-volume ratio of the polycaprolactone (solid) to the hexafluoroisopropanol in the step (1) is 0.1-0.2: 1 g/ml.

Further, the concentration of the dopamine solution in the step (1) is 1-3mg/ml, and the pH value of the dopamine solution is 8.0-9.0; the standing and light-shielding treatment time is 12-36 h; the drying mode is vacuum drying, and the drying time is 18-30 h.

Preferably, the mass-to-volume ratio of the polycaprolactone to the hexafluoroisopropanol in the step (1) is 0.15 g/mL; the stirring time is 24 h.

Preferably, the pH value of the dopamine solution in the step (1) is 8.5. The dopamine solution may be pH adjusted using tris buffer.

Preferably, the concentration of the dopamine solution in the step (1) is 2 mg/mL.

Preferably, the drying manner in the step (1) is vacuum drying, and the drying time is 24 h.

The PCL nanofiber scaffold is made of polycaprolactone materials by adopting an electrostatic spinning technology, and nanofibers are randomly distributed on the scaffold and are anisotropic.

Further, the concentration of the hirudin solution in the step (2) is 5-15 mg/ml. The hirudin has CAS number of 113274-56-9 and molecular formula of C₆₆H₉₃N₁₃O₂₅And the molecular weight is 1468.53.

Further, the solvent of the PLGA solution in the step (2) is dichloromethane; the concentration of the PLGA solution is 25-75 mg/ml; the volume ratio of the hirudin solution to the PLGA solution is 1:15-1: 5; the rotation speed of the first homogenization treatment is 800-.

Further, the PVA solution in the step (2) has a mass percentage concentration of 0.5% -2%, and the volume ratio of the PVA solution to the colostrum is 0.32-0.36: 1; the mass ratio of the Polyetherimide (PEI) to the solute of the PLGA solution is 1:10-1: 2; the rotation speed of the second homogenization treatment is 12000-14000rpm, and the time of the second homogenization treatment is 1-2 min.

Further, the PVA solution in the step (3) has a mass percent concentration of 0.5% -2%; the volume ratio of the multiple emulsion to the PVA solution is 1: 4-1: 6; the stirring speed of the stirring treatment is 400-800r/min, and the stirring treatment time is 4-6 h.

Further, the mass-volume ratio of the rH-PLGA-PEI microspheres to the water in the step (3) is 40-60: 1 mg/ml.

In the step (2) and the step (3), the rH-PLGA-PEI microsphere is prepared by adopting a water-in-oil-in-water (W1/O/W2) emulsion solvent volatilization method. Wherein W1 is recombinant hirudin solution, O is PLGA dichloromethane solution, and W2 is PVA water solution.

Preferably, the rotation speed of the centrifugal washing in the step (3) is 12000rpm, the number of the centrifugal washing is 3 times, and the time of each centrifugal washing is 5 minutes.

Further, the stirring treatment in the step (4) is carried out on a shaking table, the rotating speed of the shaking table is 60-100r/min, and the stirring treatment time is 1-2 h.

Preferably, the stirring treatment time of the step (4) is 2 h.

Preferably, the drying in the step (4) is vacuum drying, and the drying time is 24h

The invention provides an rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material prepared by the preparation method.

The rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material provided by the invention is composed of a polycaprolactone nanofiber stent, a dopamine coating and rH-PLGA/PEI microspheres, wherein a layer of dopamine is deposited on the surface of PCL, and the PLGA/PEI microsphere coated with hirudin is loaded on the PCL nanofiber by utilizing the adhesion of the dopamine, so that the aims of continuous anticoagulation and rapid endothelialization promotion are fulfilled, and the repair of vascular tissues is promoted.

Compared with the prior art, the invention has the following advantages and beneficial effects:

(1) the rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material provided by the invention is obtained by loading rH-PLGA/PEI microspheres on a PCL (polycaprolactone) nano-fiber stent prepared by an electrostatic spinning technology; compared with the existing tissue engineering scaffold material, the rH-PLGA/PEI microsphere and dopamine modified small-caliber blood vessel scaffold material can promote the adhesion and proliferation of vascular endothelial cells, has the function of continuous anticoagulation, and can prevent the formation of thrombus for a long time;

(2) the rH-PLGA/PEI microsphere and the dopamine modified PCL tissue engineering scaffold provided by the invention have good biocompatibility, and the speed and the quality of vascular tissue repair are accelerated by utilizing the promotion effect and the anticoagulation of hirudin on endothelial cell adhesion and proliferation.

Drawings

FIG. 1 is a transmission electron microscope image of rH-PLGA-PEI microspheres provided in example 1 of the present invention;

FIG. 2 is an infrared spectrum of rH-PLGA-PEI microspheres provided in example 2 of the present invention;

FIGS. 3a, 3b and 3c are SEM images of rH-PLGA/PEI microspheres and dopamine modified PCL tissue engineering scaffold provided in example 2 of the present invention;

FIG. 4 is a graph showing the result of anticoagulation characterization of rH-PLGA/PEI microspheres and dopamine modified PCL tissue engineering scaffolds in example 3 of the present invention;

FIG. 5 is a graph showing the proliferation results of co-culture of rH-PLGA/PEI microspheres and dopamine-modified PCL tissue engineering scaffolds with endothelial cells in example 4 of the present invention.

Detailed Description

The following examples are presented to further illustrate the practice of the invention, but the practice and protection of the invention is not limited thereto. It is noted that the processes described below, if not specifically described in detail, are all realizable or understandable by those skilled in the art with reference to the prior art. The reagents or apparatus used are not indicated to the manufacturer, and are considered to be conventional products available by commercial purchase.

Example 1

The method comprises the following steps: preparation of PCL nanofiber scaffold

Adding polycaprolactone into hexafluoroisopropanol, stirring for 12h to prepare a spinning solution, and preparing a PCL nanofiber scaffold by using an electrostatic spinning technology, wherein the PCL/hexafluoroisopropanol is 1.5g/15 ml; wherein, the distance between the spinning needle and the receiving iron plate is adjusted to be 18 cm; the flow rate of the spinning solution in the injection pump is 2ml/h, and the liquid amount is adjusted to 8 ml; the rotating speed of the rotating motor is adjusted to be 100 revolutions per minute, and after the power supply is switched on, the voltage of the high-voltage direct-current generator is adjusted to be 11 kv; turning on a power supply of a rotating motor, turning on a switch of an injection pump, spraying the nanofiber bundle from a spinning needle, continuously spraying for 240 minutes after the spinning is stable, and turning off the switch of the injection pump and the power supply of the motor in sequence after the spinning is finished to obtain a PCL nanofiber support;

step two: preparation of rH-PLGA-PEI microsphere

Using water-in-oil-in-water (W)₁/O/W₂) Preparing rH-PLGA-PEI microspheres by an emulsifying solvent volatilization method; wherein, W₁Is 600 μ l hirudin solution (10mg/ml), O is PLGA dichloromethane solution, specifically 200mg PLGA is dissolved in 3ml dichloromethane solvent, and W is₂10ml of PVA water solution with the mass percent concentration of 0.5 percent; firstly, W is₁Pouring into O, stirring with a homogenizer at 10000rpmStirring for 10s to form colostrum W₁O; then the colostrum W is mixed₁O pouring into W₂Then 20mg of PEI (polyethyleneimine) was added and stirred with a homogenizer at 12000rpm for 30s to form W₁/O/W₂Re-emulsifying, and stirring for 4 hours at the speed of 600 r/min; pouring into a centrifugal tube, centrifugally washing for 3 times at 12000rpm for 5 minutes each time, and freeze-drying in a freeze dryer to obtain rH-PLGA-PEI microspheres; the transmission electron microscope image of the prepared rH-PLGA-PEI microsphere is shown in fig. 1, and compared with the blank PLGA microsphere, the PLGA wraps the solid part of the hirudin, and PEI forms a layer of halo on the negative PLGA microsphere because of the positive charge. The rH-PLGA microspheres can be prepared according to the rH-PLGA-PEI microspheres, the only difference is that PEI (polyethyleneimine) is not added in the preparation process, and the rest steps are the same.

Step three: preparation of PDA-PCL (Poly (p-phenylene Ether-polycaprolactone) nanofiber scaffold)

Preparing a DOPA solution (dopamine solution) with the concentration of 2mg/ml, wherein a solvent is a Tris-HCL buffer solution, and the pH value of the DOPA solution is 9.0; immersing the PCL nanofiber in the prepared DOPA solution for 18h, then clamping, washing for 3 times by using deionized water, and drying in a vacuum oven at the drying temperature of 40 ℃ for 24h to obtain the PDA-PCL nanofiber scaffold;

step four: rH-PLGA-PEI microsphere loaded on PDA-PCL nano fiber scaffold

Adding the prepared rH-PLGA-PEI microsphere into distilled water to form a microsphere suspension of 50mg/ml, adding the prepared and dried PDA-PCL nanofiber scaffold, rotating the shaking table at a low speed for 1h, wherein the rotating speed of the shaking table is 100r/min, washing the shaking table with distilled water for 3 times, and drying the shaking table in vacuum for 12h to obtain the rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material.

Example 2

The method comprises the following steps: preparation of PCL nanofiber scaffold

Adding polycaprolactone into hexafluoroisopropanol, stirring for 24 hours to prepare a spinning solution, and preparing a PCL nanofiber scaffold by using an electrostatic spinning technology, wherein the PCL/hexafluoroisopropanol is 2g/15 ml; wherein, the distance between the spinning needle and the receiving iron plate is adjusted to be 18 cm; the flow rate of the spinning solution in the injection pump is 2ml/h, and the liquid amount is adjusted to 8 ml; the rotational speed of the rotary electric machine was adjusted to 100 revolutions per minute. After the power supply is switched on, the voltage of the high-voltage direct-current generator is adjusted to 11 kv; turning on a power supply of a rotating motor, turning on a switch of an injection pump, spraying the nanofiber bundle from a spinning needle, continuously spraying for 240 minutes after the spinning is stable, and turning off the switch of the injection pump and the power supply of the motor in sequence after the spinning is finished to obtain a PCL nanofiber support;

step two: preparation of rH-PLGA-PEI microsphere

Using water-in-oil-in-water (W)₁/O/W₂) Preparing rH-PLGA-PEI microspheres by an emulsifying solvent volatilization method; wherein, W₁Is 600 μ l hirudin solution (10mg/ml), O is PLGA dichloromethane solution, specifically 200mg PLGA is dissolved in 3ml dichloromethane solvent, and W is₂10ml of PVA water solution with the mass percent concentration of 0.5 percent; firstly, W is₁Pouring into O, and stirring at 10000rpm of homogenizer for 10s to obtain colostrum W₁O; then the colostrum W is mixed₁O pouring into W₂Then 50mg of PEI (polyethyleneimine) was added and stirred with a homogenizer at 15000rpm for 30s to form W₁/O/W₂Re-emulsifying, and stirring for 4 hours at the speed of 600 r/min; pouring into a centrifugal tube, centrifugally washing for 3 times at 12000rpm for 5 minutes each time, and freeze-drying in a freeze dryer to obtain rH-PLGA-PEI microspheres; the infrared image of the prepared rH-PLGA-PEI microsphere is shown in figure 2, and it can be seen that the addition of PEI makes the characteristic peak of hirudin appear more obvious, which indicates that the positively charged PEI successfully adsorbs more hirudin on the surface, and compared with the rH-PLGA microsphere, the rH-PLGA-PEI microsphere can load more hirudin.

Preparing a DOPA solution (dopamine solution) with the concentration of 2mg/ml, wherein a solvent is a Tris-HCL buffer solution, and the pH value of the DOPA solution is 8.5; immersing the PCL nanofiber in the prepared DOPA solution for 24 hours, then clamping, washing with deionized water for 3 times, and drying in a vacuum oven at the drying temperature of 40 ℃ for 24 hours to obtain the PDA-PCL nanofiber scaffold;

step four: rH-PLGA-PEI microsphere loaded on PDA-PCL nano fiber scaffold

Adding the prepared rH-PLGA-PEI microsphere into distilled water to form a microsphere suspension of 50mg/ml, adding the prepared and dried PDA-PCL nanofiber scaffold, rotating the shaking table at a low speed for 2h, wherein the rotating speed of the shaking table is 60r/min, washing the shaking table with distilled water for 3 times, and drying the shaking table in vacuum for 12h to obtain the rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material.

The prepared composite scaffold material has the appearance shown in fig. 3a, 3b and 3 c. The prepared rH-PLGA-PEI microsphere is uniformly loaded on the PDA-PCL nano fiber bracket, and the two are tightly combined.

Example 3

And testing the anticoagulant performance of the rH-PLGA/PEI microsphere and the dopamine modified small-caliber intravascular stent material. Film samples (1.0X 1.0 cm)²) The cells were placed in a reaction cup and incubated at 37 ℃ with 0.1mL of plasma (PPP) for 30 min. Plasma clotting times (i.e., APTT values) were then recorded by a fully automated coagulation analyzer and the average was taken in triplicate. The blank control group was not added with the sample membrane, and the other operating conditions and operating modes were completely the same as those of the experimental group. The APTT result is shown in figure 4, and the result shows that the rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material are prolonged by 8.8s compared with the APTT of the blank PCL, which indicates that the load of the rH-PLGA/PEI microsphere obviously improves the anticoagulation property of the PCL. PPP in the abscissa of FIG. 4 represents a blank control group, PCL represents a PCL nano-fiber scaffold, PDA-PCL represents a PDA-PCL nano-fiber scaffold, rHNPs-PDA-PCL represents rH-PLGA/PEI microspheres and dopamine modified small-caliber intravascular scaffold material.

Example 4

Testing cytotoxicity of rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material, HUVECs (human vascular endothelial cells) are tested at the rate of 1.5 multiplied by 104/cm²The density of the HUVECs is inoculated in a 24-well plate, and after the HUVECs and the stent to be detected are cultured for 1, 3 and 5 days respectively, the proliferation condition of the HUVECs on the stent to be detected is detected by adopting a CCK-8 kit. The specific operation is as follows: taking out the well plate, sucking out the culture medium, adding PBS buffer solution, rinsing the well plate for 2-3 times, adding 300uL of CCK-8 working solution (CCK-8 stock solution and complete culture medium are mixed at a volume ratio of 1: 9) into each well under the condition of keeping out of the light, placing the well plate at 37 deg.C, and adding 5% CO₂And incubating for 1h in an incubator in the dark. 100uL of the incubated solution was taken from each well by the double-well method and added to a new 96-well plate, and the absorbance at 450nm of each scaffold was measured using a microplate reader. Each set was set up with 4 replicates. The results are shown in FIG. 5, from day 1 to day 7, HUVECs cultured on the rH-PLGA/PEI microsphere and the dopamine modified PCL composite scaffold proliferated significantly compared with PCL control group, which indicates that both the rH-PLGA/PEI microsphere and the dopamine modified PCL composite scaffold (rH-PLGA/PEI microsphere and dopamine modified small-bore intravascular scaffold material) can promote the growth and proliferation of cells. PCL in figure 5 represents PCL nano-fiber scaffold, rHNPs-PDA-PCL represents rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular scaffold material.

The above examples are only preferred embodiments of the present invention, which are intended to be illustrative and not limiting, and those skilled in the art should understand that they can make various changes, substitutions and alterations without departing from the spirit and scope of the invention.

Claims

1. A preparation method of a small-caliber intravascular stent material modified by rH-PLGA/PEI microspheres and dopamine is characterized by comprising the following steps:

(1) adding polycaprolactone into hexafluoroisopropanol, uniformly stirring to obtain a spinning solution, and preparing the PCL nanofiber scaffold by using an electrostatic spinning technology; soaking the PCL nano fiber scaffold in a dopamine solution for standing and light-shielding treatment, taking out, washing and drying to obtain a PDA-PCL nano fiber scaffold;

(2) mixing the hirudin solution with the PLGA solution, and performing primary homogenization treatment to obtain primary emulsion; then pouring the primary emulsion into a PVA solution, adding polyetherimide, and carrying out secondary homogenization treatment to obtain a multiple emulsion;

(3) dripping the multiple emulsion obtained in the step (2) into a PVA solution, stirring, centrifugally washing, and freeze-drying to obtain rH-PLGA-PEI microspheres; adding the rH-PLGA-PEI microspheres into water, and uniformly mixing to obtain a suspension;

(4) and (3) soaking the PDA-PCL nanofiber scaffold in the step (1) in the suspension in the step (3), stirring, taking out the scaffold, washing and drying to obtain the rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material.

2. The method for preparing rH-PLGA/PEI microspheres and dopamine modified small-caliber intravascular stent material according to claim 1, wherein the mass-to-volume ratio of polycaprolactone to hexafluoroisopropanol in step (1) is 0.1-0.2: 1 g/ml.

3. The method for preparing rH-PLGA/PEI microspheres and dopamine-modified small-caliber intravascular stent material according to claim 1, wherein the concentration of the dopamine solution in the step (1) is 1-3mg/ml, and the pH value of the dopamine solution is 8.0-9.0; the standing and light-shielding treatment time is 12-36 h; the drying mode is vacuum drying, and the drying time is 18-30 h.

4. The method for preparing rH-PLGA/PEI microspheres and dopamine modified small-caliber intravascular stent material according to claim 1, wherein the concentration of the hirudin solution in the step (2) is 5-15 mg/ml.

5. The method for preparing rH-PLGA/PEI microspheres and dopamine modified small-caliber intravascular stent material according to claim 1, wherein the solvent of the PLGA solution in the step (2) is dichloromethane; the concentration of the PLGA solution is 25-75 mg/ml; the volume ratio of the hirudin solution to the PLGA solution is 1:15-1: 5; the rotation speed of the first homogenization treatment is 800-.

6. The method for preparing rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material according to claim 1, wherein the PVA solution in the step (2) has a mass percentage concentration of 0.5-2%, and the volume ratio of the PVA solution to colostrum is 0.32-0.36: 1; the mass ratio of the polyetherimide to the solute of the PLGA solution is 1:10-1: 2; the rotation speed of the second homogenization treatment is 12000-14000rpm, and the time of the second homogenization treatment is 1-2 min.

7. The method for preparing rH-PLGA/PEI microspheres and dopamine-modified small-caliber intravascular stent material according to claim 1, wherein the PVA solution of the step (3) has a mass percent concentration of 0.5-2%; the volume ratio of the multiple emulsion to the PVA solution is 1: 4-1: 6; the stirring speed of the stirring treatment is 400-800r/min, and the stirring treatment time is 4-6 h.

8. The method for preparing rH-PLGA/PEI microspheres and dopamine modified small-caliber intravascular stent material according to claim 1, wherein the mass-to-volume ratio of the rH-PLGA-PEI microspheres to water in the step (3) is 40-60: 1 mg/ml.

9. The method for preparing rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material according to claim 1, wherein the stirring treatment in step (4) is performed on a shaking table, the rotation speed of the shaking table is 60-100r/min, and the stirring treatment time is 1-2 h.

10. An rH-PLGA/PEI microsphere and dopamine modified small-caliber intravascular stent material prepared by the preparation method of any one of claims 1 to 9.