CN105232182A - Paclitaxel-loaded ethylene-vinyl acetate esophageal stent and preparation method thereof - Google Patents

Abstract

The invention belongs to the field of medical devices, and discloses an ethylene-vinyl acetate esophageal stent loaded with paclitaxel and a preparation method thereof; the stent is composed of a bare metal stent and a coating covering the bare metal stent, and the coating includes Ethylene-vinyl acetate backing layer and paclitaxel drug film layer; the inner side of the ethylene-vinyl acetate backing layer is closely attached to the bare metal stent, and the outer side of the ethylene-vinyl acetate backing layer is in contact with the paclitaxel drug film layer. Film bonding. The theoretical drug-loading capacity of the stent is 50%, and the measured drug-loading capacity is 48.26-50.81%. Within 80 days, the cumulative release of paclitaxel was 615.274-1101.368 μg/cm ² , and the penetration from the backing layer was 57.93-108.59 μg/cm ² . The preparation method of the invention is simple and easy, the mechanical properties are good, and it can play a long-term slow-release effect. The bracket has good mechanical support and the effect of preventing tumor growth.

Description

A paclitaxel-loaded ethylene-vinyl acetate esophageal stent and its preparation method

technical field

The invention relates to a drug-loaded polymer film-covered stent in the field of medical devices, in particular to an ethylene-vinyl acetate esophageal stent loaded with paclitaxel and a preparation method thereof, which are applied to the treatment of esophageal lumen strictures.

Background technique

Stents are an ideal drug delivery system. Traditional stents do not have a positive therapeutic effect, but only play a palliative role in mechanical support and short-term maintenance of cavity opening. Compared with ordinary bare metal stents, drug-loaded stents add two parts, one is drugs, which can inhibit intimal hyperplasia and prevent restenosis; the other is drug carriers, which are often synthetic polymers with good biocompatibility . Drug release from the drug-loaded layer must be controlled and predictable. To achieve this goal, it is necessary to select a suitable drug-loading material. In the non-vascular field, there is no drug-loaded stent product on the market with significant anti-tumor efficacy, so it is meaningful to analyze and study the drug-loaded stent delivery system.

After searching the literature of the prior art, it was found that the Chinese patent publication number is CN2638761Y, the publication date is September 8, 2004, and the patent name is esophageal drug stent, which is a kind of stent implanted into the narrow segment of esophagus tumor by a conveyor. The traditional esophageal drug stent has the disadvantages of insufficient drug loading, and the second is that the release of 5-fluorouracil in the silicone rubber film is slow. Guo Shengrong's research group at Shanghai Jiaotong University created a stent/drug combination for esophageal cancer, and published a series of articles including LeiL, LiuX, GuoS, TangM, ChengL, TianL. (1):45–53.doi:10.1016/j.jconrel.2010.05.017.GuoQH,GuoSR,WangZM.Estimation of 5-fluorouracil-loadedethylenevinylacetate test coating based on percolation thresholds.IntJPharm2007;333:95e102. Tumor drug film stents have been studied and achieved good results. The shortcomings of the current research are that the type of EVA used is single, the choice of the backing layer is lack of basis, and the release of paclitaxel in the membrane material is slow, which cannot effectively regulate and control the release of the drug.

Contents of the invention

Aiming at the defects in the prior art, the object of the present invention is to provide an ethylene-vinyl acetate esophageal stent loaded with paclitaxel and a preparation method thereof, improve the drug film layer and the backing layer of the stent, and enable the stent to achieve better mechanical support performance and adjustable drug release properties.

The purpose of the present invention is achieved through the following technical solutions:

In a first aspect, the present invention provides an ethylene-vinyl acetate esophageal stent loaded with paclitaxel, the stent is composed of a bare metal stent and a coating covering the bare metal stent, and the coating includes an ethylene-vinyl acetate backing Lining layer and paclitaxel drug film layer, wherein the inner side of the ethylene-vinyl acetate backing layer is closely attached to the bare metal stent, and the outer side of the ethylene-vinyl acetate backing layer is bonded to the paclitaxel drug film layer .

Preferably, the bare metal stent is selected from self-fabricated stents or commercially available stents, the material of the stent includes Ni-Ti alloy, and the model of the stent is selected from a length of 3.5 cm and a diameter of 0.9 cm.

Preferably, in the ethylene-vinyl acetate backing layer, the model of the ethylene-vinyl acetate includes one or more of EVA42/60, EVA32/43, and EVA30/10. The amount of paclitaxel saturated solution passing through three types of membranes with the same thickness and the same type with different thicknesses was investigated. Among them, the EVA30/10 film has better maximum tensile strength and poor drug permeability.

More preferably, in the ethylene-vinyl acetate backing layer, the type of the ethylene-vinyl acetate is EVA30/10, and the thickness is 50-150 μm.

Preferably, the components of the paclitaxel drug film layer include ethylene-vinyl acetate and paclitaxel. Further, the dose range of paclitaxel in the ethylene-vinyl acetate esophageal stent is 48.26-50.81%. During the implementation of the present invention, if the dose of paclitaxel is too low, the drug loading capacity will be reduced, and if the dose is too high, the drug transport and the mechanical properties of the stent will be affected.

Preferably, the model of the ethylene-vinyl acetate includes EVA42/60, EVA32/43 or EVA30/10.

More preferably, the thickness of the paclitaxel film layer is 170-180 μm.

The stent provided by the invention is an esophageal stent with one-way drug release performance. Within 80 days, the cumulative release of paclitaxel was 615.274-1101.368 μg/cm ² , and the penetration from the backing layer was 57.93-108.59 μg/cm ² . The stent of the present invention improves the series of esophageal stents prepared by my research group. The preparation method is simple and easy. The mechanical properties of the stent drug film of the present invention are better, and can play a long-term sustained release effect. The stent has good mechanical support and prevents tumors The effect of internal growth.

In a second aspect, the present invention provides a method for preparing the paclitaxel-loaded ethylene-vinyl acetate esophageal stent, comprising the step of covering the outer surface of the bare metal stent with an ethylene-vinyl acetate backing layer to prepare a metal stent covered with a backing layer, and a step of adhering a paclitaxel drug film layer on the surface of the metal stent covered with a backing layer.

Preferably, in the step of preparing a metal stent covered with a backing layer by covering the outer surface of the bare metal stent with an ethylene-vinyl acetate backing layer, the covering mainly adopts a dipping method, that is, immersing the bare metal stent in the The scaffolds were dipped in a solution of ethylene-vinyl acetate in dichloromethane.

Further, the preparation of the dichloromethane solution dissolved with ethylene-vinyl acetate includes: dissolving 4.0g EVA in every 30ml of dichloromethane, 37°C (the experiment was carried out at this temperature, simulating the temperature of the human esophagus) water bath Place in a shaker overnight, vortex, and obtain; the soaking time is 2-10s.

Preferably, in the step of adhering the paclitaxel drug film layer on the surface of the metal stent covered with the backing layer, the preparation method of the paclitaxel drug film layer mainly adopts thermal mixing followed by orientation or hot pressing.

Further, the bonding method mainly adopts heating and pressure.

In the third aspect, the present invention provides a method for quantitative analysis of paclitaxel in the paclitaxel drug film layer, comprising: fully dissolving the drug film layer in dichloromethane, adding methanol to precipitate polymers, and finally analyzing and determining by HPLC.

In the present invention, a new method for measuring the dosage of paclitaxel in the EVA drug film is established, that is, after the drug film is completely dissolved, the macromolecule is precipitated, and then the content of paclitaxel in the solvent is determined by an HPLC analysis method. Results The drug loading was about 50%, the RSD values of the dose and content uniformity of the drug film were all within 5%, and the orientation and compression of the drug film after hot mixing were relatively uniform.

The invention studies the mechanical properties of different prescription medicine films. The mechanical properties of different prescription drug films were different. The lower the VA content, the maximum tensile strength and elastic modulus of the stent drug film showed an upward trend, while the maximum elongation decreased. The maximum tensile strength of the oriented film is larger than that of the direct compression film, and it has better mechanical properties.

The invention investigates the release performance of paclitaxel in different prescription drug films. As can be seen from the drug release curves, all drug release curves present two characteristic phases, a fast drug release phase at the initial stage (1-10 days) and a slow drug release phase at the later stage (10-80 days). The cumulative release of paclitaxel from the oriented EVA42/60 drug film was 1101.368μg/cm ² , the cumulative release from the oriented EVA32/43 drug film was 721.799μg/cm ² , and that from the oriented EVA30/10 drug film The accumulative release of 615.274μg/cm ² , the cumulative release from direct heat-pressed EVA32/43 film is 783.441μg/cm ² . It can be seen that the difference in EVA film material and the orientation of the drug film make the release amount of the drug different.

The invention records the surface macroscopic morphology of the drug-loaded stent coating before and after release. The prepared stent membrane was smooth and even, but after 80 days of slow release in pH6.5 phosphate buffer containing 1% Tween 80, the surface morphology of the membrane also changed. The membrane obviously swelled, some membranes had many small bubbles on the surface, and some membranes had cracks on the surface.

The present invention observes before and after drug release with a scanning electron microscope, and it can be clearly seen from the photos that many particles are distributed on the membrane surface before the release test. After more than ten days of release, the particles distributed on the membrane can still be seen, but small holes appear in some places. After 80 days of release, it is found that the particles that originally existed on the surface of the membrane have disappeared, and more and larger holes have formed on the surface, and even the surface can be seen Shedding of flakes.

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

(1) By using hot pressing and orientation methods, the thickness of the drug film on the ethylene-vinyl acetate stent can be very thin, reaching 170 μm to 180 μm.

(2) By dipping method and controlling the soaking time, backing layers with different thicknesses can be prepared, reaching 50 μm to 150 μm.

(3) By improving the determination method of paclitaxel in the drug film, the measured value of the paclitaxel dosage in the drug film is more accurate.

(4) By comparing the permeability of paclitaxel saturated solution through different matrix EVA, the same thickness (100 μm) membrane material and through EVA30/10, different thickness membrane materials, it is determined that EVA30/10 is the membrane material, and the thickness is 100 μm. Excellent backing layer condition.

(5) Through the release experiments of paclitaxel from the drug film layer of different EVA film materials and the oriented and non-oriented EVA32/43 drug film layers, it was found that changing the polymer material or the orientation of the drug film can adjust the release of the drug to varying degrees .

Description of drawings

Other characteristics, objects and advantages of the present invention will become more apparent by reading the detailed description of non-limiting embodiments made with reference to the following drawings:

Fig. 1 paclitaxel saturated solution sees through different matrix EVA, the time-dosage curve of same thickness (100 μ m) membrane material;

Figure 2 The time-dosage curves of paclitaxel saturated solution permeating EVA30/10, membrane materials with different thicknesses;

Fig. 3 medicine releases from the medicine film layer of different EVA membrane materials and sees through the time-dose curve (n=3) of backing layer;

Fig. 4 medicine releases from the EVA32/43 drug film layer of orientation and non-orientation and sees through the time-dose curve (n=3) of backing layer;

Fig. 5 Macroscopic pictures of stent coating: Film4 in PBS release medium before experiment and after release for 80 days (a and f);

Fig. 6 Scanning electron micrographs of drug-loaded film on the film surface of drug release 0d, 10d, 30d, 80d: Film2 drug release 0d, 10d, 30d and 80d (a, b, c and d).

detailed description

The present invention will be described in detail below in conjunction with specific embodiments. The following examples will help those skilled in the art to further understand the present invention, but do not limit the present invention in any form. It should be noted that those skilled in the art can make several modifications and improvements without departing from the concept of the present invention. These all belong to the protection scope of the present invention.

Example 1

This embodiment relates to the preparation of the backing layer, and the specific operations are as follows:

Weigh about 4.0g of EVA and dissolve it in 30ml of dichloromethane solution, place it in a water-bath shaker at 37°C overnight, then take it out, and vortex for about 10min until the EVA is completely dissolved to obtain a backing layer solution.

Put a braided 3.5cm long, 0.9cm in diameter Ni-Ti alloy bare metal stent with a diameter of 1.1cm in expansion ports at both ends on a glass rod with a diameter of 0.9cm, and slowly immerse in the prepared backing layer polymer solution for 2s~ 10s, take it out and volatilize in the fume hood for 24 hours, take it off the glass rod for use, and get the metal bracket covered with the backing layer.

Example 2

The present embodiment relates to the preparation of drug film, concrete operation is as follows:

According to the formula that the ratio of polymer material to paclitaxel is 1:1, feed and mix with the hacker machine. The specific operation steps are: raise the temperature of the feeding chamber of the hacker KAAKEMiniLabII to 85°C, add EVA, start the hacker machine, and rotate to clean Feeding chamber. The above steps can be repeated many times to ensure that the feeding chamber is clean. After fully cleaning the Hack machine, add the prescription ingredients corresponding to the prescription numbers in the table, and mix for 30 minutes. After mixing, put a polyester film of a certain size under the feeding chamber, then open the feeding chamber, and scrape the mixture while it is hot. .

Example 3

This embodiment relates to the pressing and orientation of the drug film, and the specific operations are as follows:

(1) The carrier material is EVA42/60, and the drug film with a drug loading capacity of 50% is pressed under a film press at 100°C to about 340 μm and 320 μm, with an initial length of 2.5 cm, and at a constant temperature of 80°C, at a speed of 2.5min/r Stretch on the orientation machine, stretch orientation 2.4 times and 2.35 times, about 6.0cm and 5.8cm long. When it reaches about 180 μm, cool at room temperature for 30 minutes, remove it from the orientation machine, and cut it for later use.

(2) The carrier material is EVA32/43, and the drug film with a drug loading capacity of 50% is pressed under a film press at 100°C for about 1.5 hours to about 350 μm, with an initial length of 2.5 cm. Cut into two parts, one part was pressed at 100°C for about 2 hours to reach a thickness of about 180 μm, cooled at room temperature for 30 minutes, and cut for later use.

(3) The measured initial length of another EVA32/43 film is 2.1 cm, and it is stretched and oriented at a speed of 2.5 min/r at 80°C. When the orientation is doubled, cracks appear, and the cracks are cut off, oriented at 90°C, and the length is about 4.7cm. When it reaches about 180 μm, cool at room temperature for 30 minutes, remove it from the orientation machine, and cut it for later use.

(4) The carrier material is EVA30/10, and the drug film with a drug loading capacity of 50% is pressed under a film press at 120°C for about 4 hours to about 350 μm, with an initial length of 2.5 cm. Under the condition of 80 ℃, 2.5min/r speed stretching orientation 2.5 times, about 5.5cm in length, reaching about 180μm, cooling at room temperature for 30min, taking it off from the orientation machine, cutting it for later use.

Example 4

This embodiment relates to the preparation of drug-loaded stents, and the specific operations are as follows:

The cut drug film (prepared in Example 3) was heated by a fan and pressed with tweezers, and the drug film was bonded to the metal support covered with a backing layer (prepared in Example 1). Place it under a UV lamp for 10 minutes, seal it well, and set it aside.

Example 5

The present embodiment relates to the mensuration of drug film thickness, concrete operation is as follows:

Prepare all kinds of medicine films (prepared in embodiment 3), Film1, Film2, Film3 are the EVA42/60 that orientation obtains respectively, EVA32/43, EVA30/10 medicine film, Film4 is the EVA32/43 medicine film that obtains after hot pressing . Take 5 points at random in the middle and around the film, measure the thickness at each point with a thickness gauge, record the thickness number, and calculate the average thickness and thickness uniformity of the film. See attached table 1 for the results. It can be seen from Table 1 that the average thickness of the drug film after orientation and hot pressing is 170 μm to 180 μm, and the drug film prepared by the modified method is relatively uniform.

Table 1 The thickness of the drug film covered by the stent

Polymer model in the drug film Preparation Drug loading(%) Thickness (μm±SD%) EVA42/60 orientation 50 178 ± 3.87 EVA32/43 orientation 50 172 ± 2.86 EVA30/10 orientation 50 176 ± 3.13 EVA30/10 hot pressing 50 180 ± 1.19

Example 6

This embodiment relates to the determination of the drug dosage and content uniformity of the loaded PTX drug film, and the specific operations are as follows:

The prepared paclitaxel-loaded drug film (prepared in Example 3) was randomly cut out small circular film samples, 4 in each group (n=4), and precisely weighed with an electronic balance. After weighing, it was fully dissolved in 5ml of dichloromethane, and slowly dropped into 20ml of methanol. Vortex for 1min, centrifuge at 10000r for 10min. Dilute it 5 times with dichloromethane:methanol at 1:4 and then use HPLC for sample injection. The drug loading (%) in the small circular membrane sample is represented by the ratio of the value measured by HPLC to the mass of the small circular membrane sample. The results are shown in attached table 2. It can be seen from table 2 that the measured value of the content is relatively close to the theoretical value, the uniformity of the content is good, and the drug is evenly distributed in the film. The method for preparing the drug film is convenient and feasible.

Table 2 The drug content of paclitaxel drug-loaded film (n=3)

Example 7

The present invention relates to the mechanical property research of covered stent (prepared in embodiment 4), concrete operation is as follows:

The mechanical test of the sample was carried out on a universal tensile testing machine (Instron4465, Instron Corp., USA) according to ^GB1039-1992 (corresponding to ISO527-1995). Sample fracture. Measure tensile strength, elastic modulus, elongation respectively. Tensile strength is the maximum load (kg/cm ² ) borne by the original cross-sectional unit area of the effective part of the sample during the test; elongation at break During the test, when the sample breaks due to stretching, the percentage of the increase in the distance between the effective part of the sample and the initial gauge length; the material is in the elastic deformation stage, and its stress and strain become proportional Relationship (i.e. conform to Hooke's law), its proportional coefficient is the modulus of elasticity. Each sample is repeated 3 times. The results are shown in attached table 3, as can be seen from table 3, the drug film with high VA content in the three kinds of EVA materials is compared with VA The drug film with low content has better elasticity, but the resistance to external force is poor. The drug film prepared by EVA30/10 has stronger tensile strength and better mechanical properties, and can reduce the damage of the drug film in related experiments. Orientation Compared with the direct compression of the drug film, the drug film is less elastic, but stronger against external forces.

Table 3 Mechanical property parameters of stent drug film

Film composition Maximum tensile strength (Mpa) Maximum elongation (%) Elastic modulus (Mpa) EVA42/60 (orientation) 1.56 ± 2.64 546.87 ± 2.45 72.82 ± 1.87 EVA32/43 (orientation) 2.96 ± 1.76 210.02 ± 1.36 196.24 ± 2.89 EVA30/10 (orientation) 6.52 ± 1.57 200.80 ± 2.57 358.63 ± 3.42 EVA32/43 (hot press) 1.87 ± 2.89 404.54 ± 3.09 255.97 ± 2.21

Example 8

This embodiment relates to the determination of the permeability of paclitaxel in different prescription EVA blank membranes, and the specific operations are as follows:

(1) The flux of the paclitaxel saturated solution through the backing layer and the drug film matrix material was measured with a VC horizontal diffusion cell. The effective diffusion area of the horizontal diffusion cell is 0.64cm ² . Prepare a 100 μm EVA blank film by casting method, cut the blank film of EVA42/60, EVA32/43, EVA30/10 into a disc with a diameter of 1.0 cm, clamp it with a sealing ring and fix it in the supply pool of the VC horizontal diffusion instrument between the receiving pool. Add 3ml of a water-ethanol (40:60) saturated solution of paclitaxel to each supply pool, and add 3ml of a water-ethanol (40:60) solution to each receiver pool. The openings of the supply pool and the receiving pool are sealed, and the whole device is connected with constant temperature circulating water to maintain its temperature at 37°C. Both the supply pool and the receiving pool are placed in magnetons for magnetic stirring. At regular intervals, all the solutions in the receiving pool were taken out, and the concentration of paclitaxel was determined by HPLC. At the same time, add 3ml of fresh water-ethanol (40:60) solution to the receiving tank. Three parallel experiments were performed for each sample film. The results are shown in Figure 1. From Figure 1, it can be seen that in the EVA film with higher VA content, the permeability of paclitaxel is better, and the amount of drug permeated is more.

(2) EVA30/10 blank films with different thicknesses were prepared by casting method, and blank films with thicknesses of 50, 100, and 150 μm were obtained respectively. Clamp it with a sealing ring and fix it between the supply pool and the receiving pool of the V-C horizontal diffuser. The concentration of paclitaxel in the receiving pool was determined according to the above method, and three parallel experiments were carried out for each sample membrane. The results are shown in Figure 2. From Figure 2, it can be seen that the amount of medicine permeated by membrane materials with different thicknesses is different, and the thinner the membrane material, the easier it is for the medicine to permeate.

Example 9

According to the relevant experimental results of Example 8, this embodiment determines the preparation of the backing layer for the release experiment, and the specific operations are:

Weigh 1 g of EVA30/10, dissolve it in 30 ml of dichloromethane, place on a water-bath shaker at 37° C. overnight, and prepare a blank film by pouring. As a backing layer for release experiments, the thickness is about 100 μm.

Example 10

This embodiment relates to the investigation of the release behavior of the drug film, and the specific operations are as follows:

According to the prescription in Attached Table 4, four kinds of drug films (three copies in each group) were attached to a blank backing layer (prepared in Example 9), put into a V-C horizontal diffusion cell with circulating water at 37°C, and 3ml of release Medium (phosphate buffered saline at pH 6.5 containing 1% Tween 80, simulated pH of the physiological environment of the esophagus). Samples were taken at the following time points: 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 2d, 4d, 6d, 8d, 10d, 15d, 21d, 27d, 32d, 45d, 60d, 80d. And replenish fresh medium in time. The concentration of paclitaxel in the samples was determined by the HPLC method described above. After the measurement, the cumulative release rate and release rate of each group of drug films were calculated. The results are shown in accompanying drawings 3 and 4. It can be seen from the above figures that the cumulative release of paclitaxel from the drug film with high VA content is larger. The orientation of the drug film made the release of the drug different, and the cumulative release of paclitaxel from the compressed drug film was slightly larger than that of the oriented film. By changing the polymer material or the orientation of the drug film, the drug release can be adjusted to varying degrees.

The composition of the membrane material in the release experiment of table 4

Example 11

This embodiment relates to the macro photography before and after the release of the stent coating, specifically as follows:

A digital camera (Canon) was used to take pictures of each stent before and after the weight loss of the coated film. The time points of the shooting were 0 days and 80 days, and the changes in the macroscopic morphology of the film surface were observed. The results are shown in accompanying drawing 5, from which it can be seen that the dissolution of paclitaxel in the drug film in the release medium changes the surface morphology of the film.

Example 12

This embodiment relates to the SEM research after the release of the drug film, and the specific operations are as follows:

The surface morphology of the drug-loaded film before, during and after the release was observed by scanning electron microscope (SEM). The sample preparation method was as follows: cut a small piece of copper sheet with conductive function, and stick it on the sample stage with double-sided adhesive tape. Then take a small piece of stent coating sample and paste it on the double-sided adhesive tape (the drug-loaded stent coating drug-loading layer faces up and is pasted on the double-sided adhesive tape by the lining layer), and spray gold-palladium reagent powder for 30s with a current of 15mA , Blow off the unfixed reagent powder, and observe the surface morphology of the film sample released 0d, 10d, 30d, 80d by SEM. The results are shown in Figure 6. It can be seen from Figure 6 that with the prolongation of the release time, the amount of paclitaxel released gradually increased, and the particles that originally existed on the surface of the membrane gradually disappeared, and more and larger holes were formed on the surface.

Specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art may make various changes or modifications within the scope of the claims, which do not affect the essence of the present invention.

Claims (10)

1. an ethylene-vinyl acetate esophageal stent loaded with paclitaxel, characterized in that, the stent is composed of a bare metal stent and a coating covering the bare metal stent, and the coating includes an ethylene-vinyl acetate backing layer and paclitaxel drug film layer; wherein, the inner side of the ethylene-vinyl acetate backing layer is closely attached to the bare metal stent, and the outer side of the ethylene-vinyl acetate backing layer is bonded to the paclitaxel drug film layer . 2. The paclitaxel-loaded ethylene-vinyl acetate esophageal stent according to claim 1, wherein, in the ethylene-vinyl acetate backing layer, the models of the ethylene-vinyl acetate include EVA42/60, EVA32/43, EVA30 One or more of /10. 3. The paclitaxel-loaded ethylene-vinyl acetate esophageal stent according to claim 1, wherein the components of the paclitaxel drug film layer include ethylene-vinyl acetate and paclitaxel. 4. The paclitaxel-loaded ethylene-vinyl acetate esophageal stent according to claim 3, wherein the model of the ethylene-vinyl acetate includes EVA42/60, EVA32/43 or EVA30/10. 5. A method for preparing the paclitaxel-loaded ethylene-vinyl acetate esophageal stent according to any one of claims 1 to 4, characterized in that it comprises covering the outer surface of the bare metal stent with an ethylene-vinyl acetate backing layer to prepare a backing layer covered with a backing layer. The step of lining the metal stent, and the step of adhering the paclitaxel drug film layer on the surface of the metal stent covered with the backing layer. 6. according to the preparation method of the ethylene-vinyl acetate esophageal stent loaded with paclitaxel of claim 5, it is characterized in that, in the step of preparing the metal stent covered with backing layer on the bare metal stent outer covering ethylene-vinyl acetate backing layer , the covering mainly adopts a dipping method, that is, dipping the bare metal stent into a dichloromethane solution dissolved in ethylene-vinyl acetate. 7. according to the preparation method of the ethylene-vinyl acetate esophageal stent loaded with paclitaxel of claim 6, it is characterized in that, the preparation of the dichloromethane solution that is dissolved in ethylene-vinyl acetate is: every 30ml of dichloromethane dissolves 4.0 gEVA, obtained by vortexing overnight in a water-bath shaker at 37°C; the soaking time is 2-10s. 8. according to the preparation method of the described paclitaxel-loaded ethylene-vinyl acetate esophageal stent of claim 5, it is characterized in that, in the step of bonding the paclitaxel drug film layer on the surface of the metal stent covered with the backing layer, the paclitaxel The preparation method of the drug film layer mainly adopts orientation after hot mixing or hot pressing. 9. The preparation method of the paclitaxel-loaded ethylene-vinyl acetate esophageal stent according to claim 5 or 8, characterized in that the bonding method mainly adopts heating and pressure. 10. A method for quantitative analysis of paclitaxel in the paclitaxel drug film layer, characterized in that it comprises: fully dissolving the drug film layer in methylene chloride, then adding methanol to precipitate macromolecules, and finally analyzing and determining by HPLC.