阅读说明：本技术 一种药物球囊导管及其制备方法 (Medicinal balloon catheter and preparation method thereof ) 是由 何俊淅 徐兰馨 于 2021-08-12 设计创作，主要内容包括：本发明提供了一种药物球囊导管的制备方法,包括以下步骤：S1.活化球囊：利用冷活性等离子体对球囊表面进行活化预处理；S2.第一次涂覆药物：将药物溶液破碎成细小微粒,并将部分药物溶液均匀的喷涂于球囊表面；S3.预冷冻；S4.干燥结晶：将球囊表面的药物溶液干燥使药物外表面结晶；S5.反复涂覆药物：将剩余部分药物溶液继续重复S2～S4,直至喷涂药物达到所需药量,即得到所述药物球囊导管；其既能够提供简便、快捷、药量可控的涂层载药工艺,使得药物牢固的粘附在球囊表面上,减少药物在输送过程中的损失,又能提高药物到达靶向部位后的生物可利用度,增大药物的长期药效作用。(The invention provides a preparation method of a medicine balloon catheter, which comprises the following steps: s1, activating a balloon: carrying out activation pretreatment on the surface of the balloon by using cold active plasma; s2, coating a medicine for the first time: crushing the medicine solution into fine particles, and uniformly spraying part of the medicine solution on the surface of the balloon; s3, pre-freezing; s4, drying and crystallizing: drying the drug solution on the surface of the balloon to crystallize the outer surface of the drug; s5, repeatedly coating the medicine: continuously repeating S2-S4 on the rest part of the medicine solution until the sprayed medicine reaches the required dosage, and obtaining the medicine balloon catheter; the coating drug loading process which is simple, convenient and rapid and has controllable drug amount can be provided, so that the drug is firmly adhered to the surface of the balloon, the loss of the drug in the conveying process is reduced, the bioavailability of the drug after reaching a target part can be improved, and the long-term drug effect of the drug is increased.)

1. A preparation method of a drug balloon catheter is characterized by comprising the following steps: the method comprises the following steps:

s1, activating a balloon: carrying out activation pretreatment on the surface of the balloon by using cold active plasma;

s2, coating a medicine: crushing the medicine solution into fine particles, and uniformly spraying part of the medicine solution on the surface of the balloon;

s3, pre-freezing: freezing the balloon sprayed with the medicine at-40 to-20 ℃, and preserving heat for 10-20 min; then slowly heating to-10-0 ℃, and preserving heat for 10 min;

s4, drying and crystallizing: drying the drug solution on the surface of the balloon to crystallize the outer surface of the drug;

s5, repeatedly coating the medicine: and continuously repeating the steps S2-S4 on the rest part of the medicine solution until the sprayed medicine reaches the required dosage, thus obtaining the medicine balloon catheter.

2. The method for preparing a drug balloon catheter according to claim 1, wherein in S1, the activation pretreatment is: and (3) generating cold active plasma by using a plasma cleaning instrument to treat the surface material of the saccule.

3. The preparation method of the drug balloon catheter according to claim 2, wherein the power of the plasma cleaning instrument is 10-30w, the activation distance is 5-40mm, and the activation time is 30-60 s.

4. The method for preparing a drug balloon catheter according to claim 1, wherein a balloon surface treatment is further performed between S1 and S2, so that a plurality of storage cavities which are concave downwards are formed on the outer surface of the balloon.

5. The method for preparing a drug balloon catheter according to claim 4, wherein in S1, the size of the opening of the storage cavity at the side away from the catheter is smaller than the diameter of the hole inside the storage cavity.

6. The method for preparing a drug balloon catheter according to claim 1, wherein in S2, the drug is dissolved in an organic solvent in advance, and a drug solution is obtained by stirring, dissolving and filtering.

7. The method for preparing a drug balloon catheter according to claim 1, wherein in S2, the drug solution is broken into very small particles by using a spraying technique and/or an ultrasonic atomization technique, and then the particles are uniformly attached to the surface of the activation balloon.

8. The preparation method of the drug balloon catheter according to claim 7, wherein an ultrasonic sprayer is used in the spraying technology and/or the ultrasonic atomization technology, and the parameters of the ultrasonic sprayer are as follows: spraying for 16-30 times, ultrasonic power of 0.5-2.0w, and spraying height of 30-100 mm.

9. The method for preparing a drug balloon catheter according to claim 1, wherein in S3, compressed air is used to blow dry and crystallize the drug solution on the surface of the balloon.

10. A drug balloon catheter, characterized by being prepared by the preparation method of any one of claims 1 to 9.

Technical Field

The invention relates to the technical field of medical instruments, in particular to a medicine balloon catheter and a preparation method thereof.

Background

The invention provides a better solution for solving atherosclerosis and intravascular stenosis, which greatly improves the treatment efficiency, but has the defects of intravascular and intravascular restenosis, unsatisfactory treatment effect on small blood vessels, branched blood vessels, in-situ lesions and the like. Current approaches to restenosis include: the existing naked saccule and the medicine bracket have certain limitations, the restenosis rate of the naked saccule is high, the medicine bracket has poor treatment effect on small blood vessels and bifurcated blood vessels, and the naked saccule and the medicine bracket cannot show ideal effectiveness or safety.

The advent of Drug Eluting Balloons (DEBs) has brought new promise for addressing restenosis. Drug eluting balloons, similar to DES, essentially derive from catheter-based local drug delivery device concepts, where intimal hyperplasia is inhibited by drug carried by the balloon, but in a different manner and for different local drug durations. The existing drug dilatation balloon catheter on the market utilizes the contrast agent iopromide as a carrier and paclitaxel as a drug coating together to be coated on the balloon catheter for treating coronary vessel restenosis, so that the drug transfer rate can be improved, but the contrast agent has a certain complication occurrence rate in the diagnosis process, and cannot effectively carry lipophilic paclitaxel to enter cells through a membrane lipid bilayer because the iopromide is a large hydrophilic molecule.

The key technical point of the drug balloon is how to achieve the bonding balance between the drug coating and the balloon surface. If the adhesion between the drug coating and the balloon surface is low, the drug tends to fall off during balloon folding, or is lost during delivery into the lesion, or breaks off during inflation prior to contact with the target tissue and is washed away by the high velocity blood flow. If the adhesive force between the drug coating and the balloon surface is large, the drug is not easily transferred to the target blood vessel during the contact of the balloon and the target lesion tissue.

Therefore, how to firmly attach the drug on the surface of the balloon catheter until reaching the target site, and then quickly release and be absorbed by the target blood vessel is a problem to be solved by those skilled in the art.

Disclosure of Invention

The invention aims to provide a preparation method of a medicine balloon catheter, which can provide a simple, convenient and quick coating medicine carrying process with controllable medicine amount, so that medicines are firmly adhered to the surface of a balloon, the loss of the medicines in the conveying process is reduced, the bioavailability of the medicines after reaching a target part is improved, and the long-term efficacy of the medicines is improved.

The embodiment of the invention is realized by the following technical scheme:

a preparation method of a drug balloon catheter comprises the following steps:

s1, activating a balloon: carrying out activation pretreatment on the surface of the balloon by using cold active plasma;

s2, coating a medicine for the first time: crushing the medicine solution into fine particles, and uniformly spraying part of the medicine solution on the surface of the balloon;

s3, pre-freezing: freezing the balloon sprayed with the medicine at the temperature of-40 to-20 ℃, and preserving heat for 10-20 min; then slowly heating to-10-0 ℃, and preserving heat for 10-20 min;

s4, drying and crystallizing: drying the drug solution on the surface of the balloon to crystallize the outer surface of the drug;

s5, repeatedly coating the medicine: and continuously repeating the steps S2-S4 on the residual part of the medicine solution to obtain the medicine balloon catheter.

A medicinal balloon catheter is prepared by the above preparation method.

The technical scheme of the embodiment of the invention at least has the following advantages and beneficial effects:

1. according to the invention, the surface material of the balloon is activated by cold active plasma, so that a plurality of uniform attachment sites can be formed on the surface of the balloon, and the attachment uniformity of the medicinal solution on the surface of the balloon is improved; the drug solution is broken into tiny particles which are evenly attached to the surface of the saccule, and the drug is dried to form crystals, so that the drug is firmly attached to the surface of the saccule, the loss of the drug in the conveying process is reduced, the bioavailability of the drug after reaching a target part can be improved, and the long-term efficacy of the drug is increased.

2. The invention adopts a physical modification mode to spray the medicine, avoids the use of a medicine carrier, avoids the danger that a great amount of particles possibly block capillary vessels when the saccule is expanded, and simultaneously avoids the possible side effect of the medicine carrier on a human body.

3. The medicine balloon catheter prepared by the invention has firm and uniform coating and accurate and controllable dosage, is beneficial to reducing the loss rate of the medicine caused by flushing by blood in the conveying process, and can ensure that the medicine can quickly and sufficiently enter a target blood vessel to be absorbed and utilized by the blood vessel when the balloon is expanded.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.

Fig. 1 is a scanning electron microscope (2000 times) of a crystal on the surface of a drug coating layer in a drug balloon catheter prepared in example 3 of the present invention;

FIG. 2 is a scanning electron microscope (5000 times) of crystals on the surface of a drug coating layer in the drug balloon catheter prepared in example 3 of the present invention;

fig. 3 is a scanning electron microscope (6000 times) of the balloon surface in the drug balloon catheter prepared in embodiment 3 of the present invention;

fig. 4 is a schematic structural view of the balloon of the present invention.

Icon: 1-catheter, 2-balloon, 3-storage lumen, 4-attachment site.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.

The following describes a drug balloon catheter and a method for manufacturing the same according to an embodiment of the present invention.

A preparation method of a drug balloon catheter comprises the following steps:

s1, activating a balloon: carrying out activation pretreatment on the surface of the balloon 2 by using cold active plasma to form uniform attachment sites 4 on the surface of the balloon 2;

s2, balloon surface treatment: the outer surface of the saccule 2 is provided with a plurality of storage cavities 3 which are sunken downwards, preferably, the storage cavities 3 are positioned between two adjacent attachment sites 4, specifically, a semi-compliant saccule 2 is selected, the surface of the saccule 2 is uniformly carved with laser, a plurality of openings are uniformly carved on the surface of the saccule 2, each opening is obliquely and rotatably carved towards the inner layer of the saccule 2 by taking the opening as a circle center, so that the inwards sunken storage cavity 3 is formed on the saccule 2, and the opening of one side of the storage cavity 3, which is far away from the catheter 1, is smaller than the aperture inside the storage cavity 3; the drug is coated on the attachment site 4 on the outer surface of the balloon 2 and in the storage cavity 3. Therefore, after entering the blood vessel, the balloon can firstly release the medicine in the blood vessel by utilizing the medicine rate on the attachment site of the outer layer, and simultaneously, the long-term efficacy effect of the medicine is increased by utilizing the microcrystalline structure formed after the outer surface of the medicine coating is dried; the medicine in the storage cavity between the two attachment sites is released later due to the protection of the outer sides of the attachment sites, and after the medicine on the surface layers of the attachment sites is released, the storage cavity can be exposed outside, so that the medicine in the storage cavity is released, the medicine and the storage cavity have synergistic effect, a better slow release effect is achieved, the treatment time of the balloon is prolonged, and the formation of thrombus is reduced.

S3, coating a medicine for the first time: crushing the medicine solution into fine particles, and uniformly spraying part of the medicine solution on the surface of the balloon 2 so as to enable the attachment sites 4 on the outer surface of the balloon 2 and the storage cavity 3 to be coated with medicines; because the activation energy of the surface of the activated balloon 2 after activation treatment is higher, the medicinal solution can be uniformly soaked on the surface of the balloon 2 by a smaller contact angle;

s4, pre-freezing: freezing the balloon sprayed with the medicine at the temperature of-40 to-20 ℃, and preserving heat for 10-20 min; then slowly heating to-10-0 ℃, and preserving heat for 10-20 min;

s5, drying and crystallizing: drying the medicine on the surface of the balloon 2 at the temperature of 20-45 ℃ and the RH of 70-95% to ensure that the outer surface of the medicine is stably crystallized;

s6, repeatedly coating the medicine: and continuously repeating the steps S2-S4 on the rest part of the medicine solution until the sprayed medicine reaches the required dosage, thus obtaining the medicine balloon catheter.

The method firstly activates the surface material of the saccule, and efficiently activates the surface material of the saccule by utilizing cold active low-temperature plasma generated by a piezoelectric direct discharge technology, so that a plurality of uniform attachment sites can be formed on the surface of the saccule, and the attachment uniformity of a medicinal solution on the surface of the saccule is improved; then, the medicine solution is damaged into tiny particles which are evenly attached to the surface of the balloon by utilizing an ultrasonic spraying process, then the medicine solution is dried by pre-freezing operation and compressed air, the interfacial tension of the medicine surface is reduced, the aggregation and growth of the particles are prevented, so that the medicine forms a stable microcrystalline structure on the outer surface of the balloon, and then the medicine solution is sprayed and then pre-frozen, dried and crystallized continuously until the medicine on the surface of the activated balloon reaches the required content; the inner surface of the drug coating is firmly adhered to the surface of the balloon, and the outer surface of the drug coating can form a stable microcrystalline structure after pre-freezing and drying, so that the drug loss during drug delivery is solved, and the drug content entering a target blood vessel after the balloon is expanded can be ensured, thereby greatly improving the bioavailability of the drug after reaching a target part and increasing the long-term drug effect of the drug; importantly, the invention adopts a physical modification mode to spray the medicine, avoids the use of a medicine carrier in the prior art, avoids the danger that a great amount of particles possibly block capillary vessels when the saccule is expanded, and simultaneously avoids the possible side effect of the medicine carrier on a human body.

Further, in S1, the activation pretreatment is: the cold active plasma generated by the piezoelectric direct discharge technology is used for efficiently activating the surface material of the saccule. Preferably, in S1, the activation pretreatment is: generating cold active plasma by using a plasma cleaning instrument to treat the surface material of the saccule; wherein the plasma gas is air, N₂Ar or O₂The flow rate of the plasma gas is 0.005-0.8L/min/cm2, the discharge pressure is 10-30Pa, and the temperature is 35-55 ℃.

Further, the power of the plasma cleaning instrument is 10-30w, the activation distance is 5-40mm, and the activation time is 30-60 s.

Further, the medicine is a mixture composed of one or more of rapamycin, paclitaxel, probucol, sirolimus, pimecrolimus and everolimus in any proportion.

Further, in S2, the drug is dissolved in an organic solvent in advance, stirred, dissolved, and filtered to obtain a drug solution.

Further, the organic solvent is any one of methanol, ethanol, ethyl acetate, diethyl ether, acetonitrile, acetone, hexane, isopropanol, dichloromethane, tetrahydrofuran, ethyl formate and methyl acetate or a combination of at least two of the above.

Further, in S2, the drug solution is broken into very small particles and then uniformly attached to the surface of the activation balloon using a spray coating technique and/or an ultrasonic atomization technique.

Further, spraying is carried out by using a spraying machine, and the parameters of the spraying machine are as follows: spraying for 16-30 times, ultrasonic power of 0.5-2.0w, and spraying height of 30-100 mm.

Further, in S3, the drug solution on the surface of the balloon is blow-dried for crystallization by using compressed air.

Further, in S4, each time a layer of the drug is sprayed, the balloon is blow-dried until the desired amount of the drug on the surface of the activated balloon is reached.

A medicinal balloon catheter is prepared by the above preparation method.

Example 1

A preparation method of a drug balloon catheter comprises the following steps:

s1, mounting a component of a balloon catheter needing to be prepared with a medicine on an ultrasonic spraying machine, and expanding and rotating a balloon;

s2, using a plasma cleaning instrument to generate cold active plasma to carry out activation pretreatment on the surface of the balloon, wherein the power is 10w, the activation distance is 5mm, and the activation time is 60 s;

s3, balloon surface treatment: selecting a semi-compliant balloon, uniformly engraving the surface of the balloon by laser, uniformly engraving a plurality of openings on the surface of the balloon, and obliquely and rotatably engraving the openings to the inner layer of the balloon by taking the openings as the circle center at each opening to form an inwards-concave storage cavity on the balloon, wherein the size of the opening of one side of the storage cavity, which is far away from a catheter, is smaller than the aperture inside the storage cavity;

s4, dissolving the active drug rapamycin in an organic solvent methanol in advance, stirring and dissolving the rapamycin, and then filtering to obtain a rapamycin drug solution; setting parameters of an ultrasonic spraying machine: ultrasonic power is 2.0w, spraying height is 30mm, and spraying amount is 0.17ug/mm²Adding the treated rapamycin medicinal solution into a spraying machine, crushing into fine particles, and uniformly spraying the fine particles on the surface of the balloon so as to coat the medicine on the attachment sites on the outer surface of the balloon and in the storage cavity; in ultrasonic spraying, the longitudinal travel speed of the balloon catheter was 3mm/s and the axial rotation speed was 15 revolutions/s.

S5, pre-freezing: freezing the treated saccule at-40 deg.C, and keeping the temperature for 10 min; then slowly heating to-10 ℃, and preserving heat for 10 min;

s6, blowing the medicine solution on the surface of the balloon by using compressed air for crystallization, spraying and drying the residual medicine solution 16 times, wherein each spraying of a layer of medicine is pre-frozen and dried once, and the medicine balloon catheter is obtained.

Example 2

A preparation method of a drug balloon catheter comprises the following steps:

s1, mounting a component of a balloon catheter needing to be prepared with a medicine on an ultrasonic spraying machine, and expanding and rotating a balloon;

s2, using a plasma cleaning instrument to generate cold active plasma to carry out activation pretreatment on the surface of the balloon, wherein the power is 30w, the activation distance is 40mm, and the activation time is 30 s;

s3, balloon surface treatment: selecting a semi-compliant balloon, uniformly engraving the surface of the balloon by laser, uniformly engraving a plurality of openings on the surface of the balloon, and obliquely and rotatably engraving the openings to the inner layer of the balloon by taking the openings as the circle center at each opening to form an inwards-concave storage cavity on the balloon, wherein the size of the opening of one side of the storage cavity, which is far away from a catheter, is smaller than the aperture inside the storage cavity;

s4, pre-dissolving the probucol active drug in an organic solvent methanol, stirring and dissolving the probucol drug, and then filtering to obtain a probucol drug solution; setting parameters of an ultrasonic spraying machine: ultrasonic power is 0.5w, spraying height is 100mm, and spraying amount is 0.17ug/mm²Adding the treated probucol medicine solution into a spraying machine, crushing into fine particles, and uniformly spraying the fine particles on the surface of the balloon so that the attachment sites on the outer surface of the balloon and the storage cavity are coated with medicines; in ultrasonic spraying, the longitudinal travel speed of the balloon catheter is 1mm/s, and the axial rotation speed is 20 revolutions/s.

S5, pre-freezing: freezing the balloon coated with the medicine at-20 deg.C, and keeping the temperature for 20 min; then slowly heating to 0 ℃, and preserving heat for 20 min;

s6, blowing the medicine solution on the surface of the balloon by using compressed air for crystallization, spraying and drying the residual medicine solution 22 times, wherein each time one layer of medicine is sprayed, the medicine solution is pre-frozen and dried once, and the medicine balloon catheter is obtained.

Example 3

A preparation method of a drug balloon catheter comprises the following steps:

s1, mounting a component of a balloon catheter needing to be prepared with a medicine on an ultrasonic spraying machine, and expanding and rotating a balloon;

s2, using a plasma cleaning instrument to generate cold active plasma to carry out activation pretreatment on the surface of the balloon, wherein the power is 20w, the activation distance is 20mm, and the activation time is 40 s;

s3, balloon surface treatment: selecting a semi-compliant balloon, uniformly engraving the surface of the balloon by laser, uniformly engraving a plurality of openings on the surface of the balloon, and obliquely and rotatably engraving the openings to the inner layer of the balloon by taking the openings as the circle center at each opening to form an inwards-concave storage cavity on the balloon, wherein the size of the opening of one side of the storage cavity, which is far away from a catheter, is smaller than the aperture inside the storage cavity;

s4, dissolving the taxol active drug in the organic solvent methanol in advance, stirring and dissolving the taxol drug, and then filtering to obtain a taxol drug solution; setting parameters of an ultrasonic spraying machine: the ultrasonic power is 1.0w, the spraying height is 60mm, and each timeSpraying amount of 0.22ug/mm²Adding the treated paclitaxel drug solution into a spraying machine, crushing into fine particles, and uniformly spraying on the surface of the balloon so as to coat the drug on the attachment sites on the outer surface of the balloon and in the storage cavity; in ultrasonic spraying, the longitudinal travel speed of the balloon catheter is 5mm/s, and the axial rotation speed is 10 revolutions/s.

S5, pre-freezing: freezing the balloon coated with the medicine at-30 deg.C, and keeping the temperature for 15 min; then slowly heating to-5 ℃, and keeping the temperature for 15 min;

s6, blowing the medicine solution on the surface of the balloon by using compressed air for crystallization, spraying and drying the residual medicine solution 20 times, and pre-freezing and drying once every time when a layer of medicine is sprayed to obtain the medicine balloon catheter.

Comparative example 1

This comparative test example differs from example 3 in that: no activation pretreatment was performed on the balloon surface.

Comparative example 2

This comparative test example differs from example 3 in that: directly spraying all the medicines on the surface of the balloon at one time.

Comparative example 3

This comparative test example differs from example 3 in that: after each spraying, no pre-freezing operation is carried out.

Comparative example 4

This comparative test example differs from example 3 in that: the balloon surface was not subjected to storage chamber engraving treatment.

Experimental example 1

A scanning electron microscope image of the crystals on the surface of the drug coating in the balloon catheter prepared by the preparation method of example 3 is shown in fig. 1-2; scanning electron micrographs of the balloon surface are shown in fig. 3.

As can be seen from fig. 1-3: the medicine coating has good firmness, is complete and uniform, and has no chapping and falling off phenomena; the length range of the crystal in the drug coating is 3.6-4.75 μm, which is very uniform. The clinical safety and the effectiveness of the medicine can be fully ensured from the two points.

Experimental example 2: test of in vitro pulsation simulation test for drug coating firmness

In vitro simulation evaluation of coating firmness of the drug balloon catheters prepared in examples 1 to 3 and comparative examples 1 to 3 was performed by: 10 drug balloon catheters prepared in examples 1 to 3 and comparative examples 1 to 3 were used.

Adopting a pulsating flow simulation device to simulate the action of the drug balloon on the pulsating flow of the blood vessel in vitro (the device controls the systolic pressure of 130mmHg and the diastolic pressure of 80mmHg at the frequency of 75 times/minute), and then testing the content of the residual drug on the surface of the drug balloon by using a High Performance Liquid Chromatography (HPLC); and collecting the solution in the equipment, carrying out a particle test experiment, and detecting the firmness of the drug delamination on the surface of the balloon after the simulated pulsating flow effect. The results are shown in table 1:

TABLE 1 in vitro pulsating flow simulation test results

As can be seen from the data in Table 1: the medicines of the medicine balloon catheter in the embodiments 1 to 3 can be firmly attached to the surface of the balloon catheter, so that the loss of the medicines in the conveying process is reduced, the bioavailability of the medicines after reaching the target part can be improved, and the long-term efficacy effect of the medicines is increased. While comparative example 1 did not subject the balloon surface to an activation pretreatment; comparative example 2 all the drugs were directly sprayed onto the balloon surface at one time without a process of drying once for each layer of drug sprayed; comparative example 3 no pre-freezing operation was performed; comparative example 4 no storage cavity carving treatment was performed on the balloon surface, i.e. no storage cavity existed on the surface, none of the above could firmly attach the drug to the balloon catheter surface, and it was difficult to form a stable microcrystalline structure, so that the drug was seriously lost during the delivery process, and the bioavailability of the drug was reduced.

Experimental example 3: testing the Release Effect of drugs

After the drug balloon catheters of the above examples 1 to 3 and comparative test examples 1 to 3 were respectively expanded in a healthy pig model, the drug contents in the target blood vessel, the visceral organs and the plasma were detected by LC/MS, and the pharmacokinetic parameters of the target blood vessel tissue and the main organ were calculated.

The experimental method comprises the following steps: the density of the medicine carried by the medicine is 2 mu g/mm²After the iliac/femoral artery of the healthy pig is expanded, respectively taking blood vessels of a treatment section, a near end of the treatment section and a far end of the treatment section of the drug balloon to detect the drug content 30min, 2h, 7d, 28d and 90d after operation; detecting the concentration of the medicine in vital organs (heart, lung, liver, spleen and kidney); blood was also collected at 2h, 1d, 7d, 28d, and 90d after the treatment, and the drug concentration in the plasma was measured, and the results are shown in table 2:

TABLE 2 drug concentration in plasma (μ g/g)

	2h	1D	7D	28D	90D
						Example 1	141	80	10.21	5.23	1.08
Example 2	150	96	18.66	9.86	2.28
						Example 3	178	108	26.87	14.62	3.26
Comparative example 1	112	60	5.2	1.9	0.038
						Comparative example 2	126	78	8.7	3.4	0.042
Comparative example 3	120	96	30	5	0.122
						Comparative example 4	138	76	98.4	3.2	0.041

As can be seen from the data in Table 2: when the target blood vessel part of the drug balloon catheter in the embodiments 1-3 of the invention is in T2 h, the drug content reaches the peak value and then rapidly decreases, the drug obtains a more comprehensive drug release process on the balloon surface, and the whole release and absorption process, both short-term and long-term drug content, is far higher than the lowest effective dose of 0.047 mug/g in the prior art. And experiments show that the drug content of other tissues and organs is very low, and no adverse event caused by drug coating is found.

In the comparative example 1, the surface of the balloon is not subjected to activation pretreatment, and the release rate of the drug in the whole process from the early stage to the later stage is low, so that a good release effect cannot be achieved, and the therapeutic effect cannot be exerted basically at the later stage. Comparative example 2 all the drugs were directly sprayed onto the balloon surface at one time; the process of drying once every layer of medicine is sprayed is not carried out; the comparative example 3 does not carry out pre-freezing operation, and the comparative example 4 does not carry out storage cavity carving treatment on the surface of the balloon, namely the surface does not have a storage cavity, so that the better slow-release effect and the long-term drug effect cannot be achieved.

The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and various modifications and changes will occur to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.