CN112516439A

CN112516439A - Preparation method of drug balloon, prepared drug balloon and application thereof

Info

Publication number: CN112516439A
Application number: CN202011505979.XA
Authority: CN
Inventors: 盛卫文
Original assignee: Shanghai Xinzhi Medical Technology Co ltd
Current assignee: Shanghai Xinzhi Medical Technology Co ltd
Priority date: 2020-12-18
Filing date: 2020-12-18
Publication date: 2021-03-19

Abstract

The invention discloses a preparation method of a medicine balloon, the prepared medicine balloon and application thereof, relating to the field of medical instruments and comprising the following steps: (1) curing the elastic substance or the elastic device to the surface of the balloon to obtain the balloon with the surface modified with the elastic substance or the elastic device; (2) spraying a medicine solution, a medicine and auxiliary material mixed solution, a medicine particle suspension, a medicine and auxiliary material forming particle or randomly combined mixed particle on the balloon with the surface modified with the elastic substance or the elastic device obtained in the step (1) to obtain the balloon with the medicine coating on the surface; (3) and (3) carrying out surface solvation treatment on the balloon with the drug coating on the surface obtained in the step (2), and obtaining the drug balloon after the balloon is split and folded. The implementation of the invention solves the problem of the washout of the drug coating in the in vivo delivery process, the drug is uniformly distributed and has good firmness, and the drug particles completely or mostly enter the vascular wall tissue and are easy to play the long-acting treatment effect.

Description

Preparation method of drug balloon, prepared drug balloon and application thereof

Technical Field

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

Background

The blood vessel stenosis is easy to cause unsmooth blood flow of the blood vessel and even block the blood vessel to cause life danger, and the current main treatment methods for the blood vessel stenosis comprise the placement of a blood vessel stent and the delivery of medicine treatment through a medicine balloon. The invention of the stent provides a better solution for solving atherosclerosis and intravascular stenosis, so that the treatment efficiency is greatly improved, but the defects of intravascular and stent restenosis, unsatisfactory treatment effect on small blood vessels, bifurcated blood vessels, in-situ lesions and the like exist simultaneously. The appearance of drug eluting balloons brings new hopes for solving restenosis, essentially originates from a local drug delivery device idea based on a catheter, inhibits intimal hyperplasia through drugs carried by the balloons, and when the balloons are delivered to a diseased vessel wall and are propped open, expanded and contacted with the vessel wall intimal, the drugs are quickly released and transferred into the local vessel wall by tearing the vessel wall intimal and pressurizing. The medicine has local effect of resisting vascular intimal hyperplasia, so as to prevent vascular restenosis after vascular intervention.

In the published patent literature, CN 106237485 a discloses a method for preparing a drug-coated balloon dilatation catheter, in which a drug with a carrier is first sprayed onto the balloon surface and then a water-soluble protective layer is coated thereon. Such drug balloons reduce balloon losses to some extent during delivery, but also hinder drug release after reaching the lesion, with the result that the drug is likely not able to enter the tissue vasculature effectively. CN 106267377a discloses a drug-coated balloon catheter, the drug coating comprises an active drug and a carrier; the active drug is paclitaxel, rapamycin, a paclitaxel derivative or a rapamycin derivative; the carrier includes an organic acid salt and a polyol. The organic acid salt and the polyhydric alcohol in the drug coating act together, the particle size of the drug particles is small, and the drug is prevented from being released prematurely before the balloon catheter is placed into a target site, however, the drug coating is only attached to the surface of the balloon through simple coating, and the problem that the drug coating is washed away in the in-vivo delivery process cannot be avoided. CN106798951A discloses a preparation method of a drug eluting balloon, comprising the following steps: soaking the balloon in an inorganic saline solution for 1-1.5 hours, taking out and drying, adding water into the drug solution, stirring uniformly and standing for 1-2 minutes, then immersing the dried balloon in the drug solution for 1-2 hours, taking out and drying to obtain the drug eluting balloon. Wherein the inorganic salt aqueous solution is a sodium chloride-magnesium chloride mixed aqueous solution or a calcium chloride-magnesium chloride mixed aqueous solution, and the medicinal solution consists of a medicament, an additive and a solvent. The invention uses mixed inorganic salt water solution to promote the obtaining of smaller drug crystal particles and increase the bonding force of the drug and the balloon. There is a problem in that the drug coating obtained by dip-coating the drug is not uniformly distributed and not excellent in the fastness.

The core of the drug balloon and serving the therapeutic function is the drug coating. Since the active antiproliferative drug is a lipophilic drug, is poorly soluble in water, and easily agglomerates to form large particles, these large drug particles are easily washed off by the blood during delivery. If the number of the exfoliated microparticles is large, the amount of drug reaching the target blood vessel is reduced, and on the other hand, the exfoliated microparticles easily cause complications such as distal vascular occlusion and thrombus, and serious amputation may result. Therefore, the influence of blood vessels and blood flow on the drug balloon needs to be considered in the production process of the drug balloon. The main influencing factors include: the scouring of blood flow to the drug balloon coating, the dissolving effect of blood to the drug coating, and the friction effect of the drug balloon in the blood vessel. These several main factors correspond to the fact that the primary property of the balloon is the firmness of the coating. In addition, factors affecting the therapeutic effect of the drug balloon are the ability of the drug to be released from the drug coating to the vessel wall, the ability of the drug to enter endothelial tissue after reaching the vessel wall, and the ability to resist blood wash when not being absorbed by the tissue. This relates to the drug release rate and the penetration capacity of the drug balloon coating and the retention capacity on the vessel wall, respectively. In the prior art, the drug coating is only attached to the surface of the balloon through simple coating, the problem that the drug coating is washed off in the in-vivo conveying process cannot be avoided, and the drug coating obtained by the drug coated in a dip-coating mode is uneven in drug distribution and poor in firmness; and the drugs are difficult to enter the vascular wall tissue, or even contacting the vascular wall tissue, most drugs still cannot play a long-acting role; the retention capacity of the medicine on the vascular wall is not enough, the medicine adsorbed on the vascular wall is dangerous to be washed away by blood flow, and the medicine particles can not completely or mostly enter the vascular wall tissues, so that the long-acting treatment effect can not be exerted.

Therefore, those skilled in the art are dedicated to develop a preparation method of a drug balloon, the prepared drug balloon and application thereof, and solve the technical problem that a drug coating cannot be firmly bonded on the surface of the balloon.

Disclosure of Invention

In view of the above-mentioned drawbacks of the prior art, the technical problems to be solved by the present invention are: how to solve the coating medicine of medicine sacculus uneven distribution and firmness not good, the medicine is in the internal transportation process or is absorbed the problem that is washed off by the blood flow easily when the vascular wall.

In order to achieve the purpose, the invention provides a preparation method of a medicine balloon, which comprises the following steps:

(1) curing the elastic substance or the elastic device to the surface of the balloon to obtain the balloon with the surface modified with the elastic substance or the elastic device;

(2) spraying a medicine solution, a medicine and auxiliary material mixed solution, a medicine particle suspension, a medicine and auxiliary material forming particle or randomly combined mixed particle on the balloon with the surface modified with the elastic substance or the elastic device obtained in the step (1) to obtain the balloon with the medicine coating on the surface;

(3) and (3) carrying out surface solvation treatment on the balloon with the drug coating on the surface obtained in the step (2), and obtaining the drug balloon after the balloon is split and folded.

Further, the elastic substance or the elastic device is collagen, latex, epoxy resin, rubber, a microcoil or a metal micro-spring.

Further, in the step (1), the elastic substance or the elastic device is cured on the surface of the balloon by a photocuring method.

Further, in the step (2), the drug solution is a solution containing an active drug and a carrier.

Further, the active drug is selected from any one or a combination of at least two of rapamycin, rapamycin derivatives or paclitaxel drugs.

Further, the carrier contains amino groups and/or hydroxyl groups.

Further, the surface solvation treatment of the step (3) is carried out in a volatile organic solvent steam atmosphere.

Further, the split folding process of the step (3) comprises: the saccule with medicine coating on the surface is pressed by a machine, is pressed and held by a chuck, is divided into 3 or 6 petals by pumping negative pressure, and is rolled and held by a scroll in a negative pressure state.

Further, the invention also provides the medicine balloon prepared by the preparation method.

Further, the invention also provides the application of the medicine balloon as the device for treating in-situ stenosis or restenosis in blood vessels.

Compared with the prior art, the invention at least has the following beneficial technical effects:

according to the invention, the elastic substance or the elastic device is solidified on the surface of the balloon, then the drug coating is coated, and further the prepared drug coating of the drug balloon can be firmly combined on the surface of the balloon through solvation treatment and split folding, so that the drug coating is not easy to fall off, the problem that the drug coating is washed off in the in-vivo conveying process is solved, the drug distribution of the coating is uniform and the firmness is good, the risk that the drug adsorbed on the vessel wall is washed away by blood flow is overcome, the drug particles completely or mostly enter the vessel wall tissue, and the long-acting treatment effect is easily exerted.

The conception, the specific structure and the technical effects of the present invention will be further described with reference to the accompanying drawings to fully understand the objects, the features and the effects of the present invention.

Drawings

FIG. 1 is a schematic structural view of a drug balloon of the present invention;

wherein: 1-a fat-soluble drug; 2-an amino hydroxy-containing compound; 3-balloon body; 4-chitosan.

Detailed Description

The preferred embodiments of the present invention will be described below with reference to the accompanying drawings for clarity and understanding of technical contents. The present invention may be embodied in many different forms of embodiments and the scope of the invention is not limited to the embodiments set forth herein.

In the drawings, structurally identical elements are represented by like reference numerals, and structurally or functionally similar elements are represented by like reference numerals throughout the several views. The size and thickness of each component shown in the drawings are arbitrarily illustrated, and the present invention is not limited to the size and thickness of each component. The thickness of the components may be exaggerated where appropriate in the figures to improve clarity.

The structure of the drug balloon of the present invention is shown in fig. 1, wherein the round area is an enlarged structure of the drug coating on the balloon. In order to prepare the drug balloon, the invention provides a preparation method of the drug balloon, which comprises the following steps:

(2) spraying a medicine solution, a medicine and auxiliary material mixed solution, a medicine particle suspension, a medicine and auxiliary material forming particle or randomly combined mixed particle on the balloon with the surface modified with the elastic substance or the elastic device obtained in the step (1) to obtain the balloon with the medicine coating on the surface; the drug or drug particles can be crystalline particles formed by pure drug, amorphous particles or particles formed by mixing the two, particles formed by drug and auxiliary materials, particles formed by auxiliary materials with sustained and controlled release function, or mixed particles of any of the above particles, and the like. The drug particle size can be micro-particles, nano-particles or micro-and nano-mixed particles thereof; the shape can be sheet, spherical, square, thorn, needle or other irregular shapes; the elastic substance or the elastic emitting device is collagen, latex, epoxy resin, rubber, a microcoil, a metal micro-spring plate and the like.

The invention installs or coats elastic material or elastic emission device on the surface of saccule, then sequentially installs or coats medicine and relative findings, the outmost layer is protective layer. Meanwhile, the elastic substance or the elastic transmitting device has balloon expansion pressure induction triggering, so that the medicine or the medicine particles are transmitted and embedded into the vessel wall, and the loss of the medicine is reduced. In the invention, the elastic substance or the elastic device is solidified on the surface of the balloon, then the drug coating is coated, and then the drug coating of the prepared drug balloon can be firmly combined on the surface of the balloon through solvation treatment and split folding, so that the drug coating is not easy to fall off, and the drug is prevented from being washed off in the in-vivo delivery process.

The method for curing the elastic substance or the elastic device to the surface of the balloon in the step (1) is a photocuring method, and photocuring is performed by using ultraviolet rays. The method of photo-curing in the present invention can cure the elastic substance or elastic device to the surface of the balloon, so as to enhance the bonding firmness of the elastic substance or elastic device and the balloon. Meanwhile, the medicine or medicine particles can be ejected or emitted to quickly enter the vascular wall tissue, so that the loss of the medicine eluted and washed away by blood flow on the surface of the vascular wall tissue is avoided.

The elastic substance or the elastic device in the step (1) is collagen, latex, epoxy resin, rubber, a microcoil, a metal micro-spring plate and the like; the adhesive agent fixed or mounted on the surface of the balloon is photo-crosslinked chitosan, acrylic resin or the like so as to firmly bond with the balloon. The chitosan is unmodified chitosan or modified chitosan. The modified chitosan is modified by any one or at least two modification methods of hydroxyethylation, carboxymethylation or sulfoesterification. The molecular weight of chitosan is 2 × 10⁵-5×10⁵E.g. 2 x 10⁵、2.3×10⁵、2.5×10⁵、2.8×10⁵、3×10⁵、3.5×10⁵、3.8×10⁵、4×10⁵、4.5×10⁵、4.8×10⁵Or 5X 10⁵。

The drug solution in the step (2) is a solution containing an active drug solution, an active drug and a carrier. The medicine is an anti-intimal hyperplasia medicine for treating vascular restenosis. The active drug is selected from any one or the combination of at least two of rapamycin, rapamycin derivatives or paclitaxel drugs. The carrier contains amino and/or hydroxyl groups. The amino and/or hydroxyl can mainly promote the crystallization of the paclitaxel to form crystals, prevent the paclitaxel from being largely washed away before entering blood vessels to reach lesion sites, and on the other hand, can increase the hydrophilicity of the crystalline paclitaxel and is beneficial to the release of drugs when reaching the lesion sites and expanding. The number of amino and/or hydroxyl groups contained in a single molecule of the carrier is 2 or more, such as 2, 3, 4, 5, 6, 8, 10, 13, 15, 18, 20, 25, 30, or even more. The carrier is selected from one or combination of at least two of potassium iodide, sodium chloride, urea, nicotinamide, urethane, Tween 80, mannitol, sorbitol, lactose, galactose, meglumine, polyvinyl alcohol, polyethyleneimine or polyether polyol.

The carrier used in the invention can promote nucleation of the active drug to form crystals on one hand, can promote good dispersion of the drug on the other hand, and can form the package carrier for the active drug, so that the drug is more firmly combined on the surface of the balloon, the loss of the drug in the in-vivo delivery process is reduced, the bioavailability of the drug is favorably enhanced, and the absorption and utilization of the drug by tissues are promoted.

The drug concentration in the drug solution of step (2) is 30-50mg/mL, such as 30mg/mL, 32mg/mL, 35mg/mL, 38mg/mL, 40mg/mL, 43mg/mL, 45mg/mL, 48mg/mL, or 50 mg/mL. In preparation for controlling the amount of drug solution sprayed onto the balloon, spraying was performed using a precision injector and sprayer to obtain a uniform drug coating. And (5) controlling the process parameters to reach the expected dosage, and finishing spraying.

The solvation treatment in the step (3) is carried out in the steam atmosphere of a volatile organic solvent. The volatile organic solvent is any one or combination of at least two of methanol, ethanol, acetone, tetrahydrofuran, n-butanol, isobutanol, sec-butanol or n-hexane. The medicinal solution is prepared by using a mixture of organic solvent and water, wherein the volume ratio of the organic solvent to the water is (99-70): 1-30, such as 99:1, 95:1, 90:1, 85:1, 80:1, 70:14, 70:25, 75:25, 90:5, 90:10, 85:15, 99:15, 80:20, 80:30, 70:30 and the like. The solvation treatment is carried out at ambient temperature. The solvation treatment time is 1-120min, such as 1min, 3min, 5min, 8min, 10min, 13min, 15min, 18min, 20min, 30min, 40min, 50min, 60min, 70min, 80min, 90min, 100min, 110min or 120 min.

And (3) when the split is folded and packaged, the split number is 3 or 6. The temperature for folding and packing in the step (3) is 60-70 ℃, such as 60 ℃, 63 ℃, 6 ℃, 68 ℃ or 70 ℃. In the invention, the split folding means that the saccule is pressed by a machine and then is pressed and held by a chuck, the saccule with 3 or 6 petals is separated by negative pressure, and the folding process is finished by rolling and holding the saccule by a reel in the state of negative pressure suction of the saccule. The diameter of the medicine balloon can be reduced by utilizing the split folding, and the medicine loss can be reduced by the split folding, so that the medicine coating is not easy to wash off and is firmer. The preparation method is accurate, stable and efficient, and the prepared drug balloon has high delivery efficiency, firm combination of drug coatings and high drug utilization rate.

The invention provides the drug balloon prepared by the preparation method.

In another aspect, the present invention provides the use of a drug balloon as described above as a device for treating in situ stenosis or restenosis within a blood vessel.

To compare balloon coating firmness, the invention also provides the following examples and comparative examples.

Example 1

In this example, a drug balloon was prepared by the following method:

(1) carrying out photocuring by using ultraviolet rays to solidify chitosan (the molecular weight is about 5 multiplied by 105) with the N-deacetylation degree of 85% to the surface of the balloon to obtain the balloon with the surface modified by chitosan; the chitosan is modified by hydroxyethylation;

(2) spraying a drug solution on the balloon with the surface modified with chitosan obtained in the step (1), wherein the drug solution is a solution containing active drug paclitaxel and carrier mannitol, the drug concentration in the drug solution is 30mg/mL, in order to accurately control the amount of the drug solution sprayed on the balloon, a precise sample injector and a spraying machine are used for spraying to obtain a uniform drug coating, the expected drug amount is reached by controlling process parameters, and the balloon with the drug coating on the surface is obtained after spraying;

(3) and (3) carrying out surface solvation treatment on the balloon with the drug coating on the surface obtained in the step (2) in the steam atmosphere of volatile organic solvent propanol for 100min, and then carrying out split folding at 70 ℃ with the split number of 3 to obtain the drug balloon.

Example 2

In this example, a drug balloon was prepared by the following method:

(1) carrying out photocuring by using ultraviolet rays to solidify chitosan (the molecular weight is about 3 multiplied by 105) with the N-deacetylation degree of 70% to the surface of the balloon to obtain the balloon with the surface modified by chitosan; the chitosan is modified by carboxymethylation;

(2) spraying a drug solution on the balloon with the surface modified with chitosan obtained in the step (1), wherein the drug solution is a solution containing an active drug paclitaxel and a carrier nicotinamide, the drug concentration in the drug solution is 30mg/mL, in order to accurately control the amount of the drug solution sprayed on the balloon, a precise sample injector and a spraying machine are used for spraying to obtain a uniform drug coating, the expected drug amount is reached by controlling process parameters, and the balloon with the drug coating on the surface is obtained after spraying;

(3) and (3) carrying out surface solvation treatment on the balloon with the drug coating on the surface obtained in the step (2) in the steam atmosphere of a volatile organic solvent propanol for 30min, and then carrying out split folding at 70 ℃ with the split number of 3 to obtain the drug balloon.

Example 3

In this example, a drug balloon was prepared by the following method:

(1) carrying out photocuring by using ultraviolet rays to solidify chitosan (the molecular weight is 3 multiplied by 105) with the N-deacetylation degree of 70% to the surface of the balloon to obtain the balloon with the surface modified by chitosan; the chitosan is modified by sulfonic acid esterification;

(2) spraying a drug solution on the balloon with the surface modified with chitosan obtained in the step (1), wherein the drug solution is a solution containing active drug paclitaxel and carrier lactose, the drug concentration in the drug solution is 50mg/mL, and in order to accurately control the amount of the drug solution sprayed on the balloon, a precise sample injector and a spraying machine are used for spraying so as to obtain a uniform drug coating. The expected dosage is reached by controlling the process parameters, and the balloon with the drug coating on the surface is obtained after the spraying is finished;

(3) and (3) carrying out surface solvation treatment on the balloon with the drug coating on the surface obtained in the step (2) in the steam atmosphere of volatile organic solvent acetone for 30min, and then carrying out split folding at 70 ℃ with the split number of 3 to obtain the drug balloon.

Example 4

In this example, a drug balloon was prepared by the following method:

(1) carrying out photocuring by using ultraviolet rays to solidify chitosan (the molecular weight is 3 multiplied by 105) with the N-deacetylation degree of 70% to the surface of the balloon to obtain the balloon with the surface modified by chitosan; the chitosan is modified by carboxymethylation;

(2) spraying a drug solution on the balloon with the surface modified with chitosan obtained in the step (1), wherein the drug solution is a solution containing an active drug paclitaxel and a carrier potassium iodide, the drug concentration in the drug solution is 50mg/mL, and in order to accurately control the amount of the drug solution sprayed on the balloon, a precise sample injector and a spraying machine are used for spraying so as to obtain a uniform drug coating. The expected dosage is reached by controlling the process parameters, and the balloon with the drug coating on the surface is obtained after the spraying is finished;

(3) and (3) carrying out surface solvation treatment on the balloon with the drug coating on the surface obtained in the step (2) in the steam atmosphere of a volatile organic solvent propanol for 20min, and then carrying out split folding at 70 ℃ with the split number of 6 to obtain the drug balloon.

Example 5

In this example, a drug balloon was prepared by the following method:

(2) spraying a drug solution on the balloon with the surface modified with chitosan obtained in the step (1), wherein the drug solution is a solution containing active drug paclitaxel and carrier polyvinyl alcohol, the drug concentration in the drug solution is 45mg/mL, and in order to prepare for controlling the amount of the drug solution sprayed on the balloon, a precise sample injector and a spraying machine are used for spraying so as to obtain a uniform drug coating. The expected dosage is reached by controlling the process parameters, and the balloon with the drug coating on the surface is obtained after the spraying is finished;

(3) and (3) carrying out surface solvation treatment on the balloon with the drug coating on the surface obtained in the step (2) in the steam atmosphere of volatile organic solvent propanol for 120min, and then carrying out split folding at 70 ℃ with the split number of 3 to obtain the drug balloon.

Example 6

The only difference from example 1 is that the chitosan used was unmodified chitosan.

Example 7

The difference from example 1 was only that the chitosan used had an N-deacetylation degree of 57%.

The structure of the drug balloon prepared by the invention is shown in fig. 1, wherein an enlarged structure of a drug coating on the balloon is arranged in a circular area. The drug coating can be uniformly and firmly combined on the surface of the balloon, is not easy to fall off, avoids the drug from being washed off in the in-vivo delivery process, reduces the drug loss and improves the drug utilization rate.

Comparative example 1

This comparative example is different from example 1 only in that the degree of N-deacetylation of chitosan is 50%, and the remaining preparation method and conditions are the same as those of example 1.

Comparative example 2

This comparative example is different from example 1 only in that the drug solution described in step (2) does not contain a carrier, and the remaining preparation method and conditions are the same as those of example 1.

Comparative example 3

This comparative example is different from example 1 only in that step (1) does not cure chitosan onto the balloon using a photo-curing method, but a solution of chitosan is coated on the surface of the balloon, and the rest of the preparation method and conditions are the same as example 1.

Comparative example 4

This comparative example is different from example 1 only in that no solvation treatment was performed in step (3), and the remaining preparation methods and conditions were the same as in example 1.

Comparative example 5

This comparative example is different from example 1 only in that step (3) is not split and folded, and the drug balloon is obtained after surface solvation treatment, and the remaining preparation method and conditions are the same as those of example 1.

The coating firmness of the drug balloons prepared in examples 1 to 7 and comparative examples 1 to 5 was evaluated, method 1 being: the drug balloon prepared in the embodiment and the comparative example is placed in an in vitro simulation flushing device, PBS is adopted to simulate blood, the flow rate is 35ml/min, water bath is carried out at 37 ℃, the flushing time is 3 minutes, finally, the drugs remained on the balloon are respectively eluted and tested by HPLC, the drug residue ratio is calculated, the higher the residue ratio value is, the better the firmness is represented, and the smaller the value is, the worse the firmness is represented. Coating firmness data for drug-coated balloon catheters are listed in table 1.

TABLE 1

Example 1

Example 2

Example 3

Example 4

Example 5

Example 6

Ratio of residue to residue

80.2％

74.8％

76.7％

75.1％

79.3％

70.5％

Example 7

Comparative example 1

Comparative example 2

Comparative example 3

Comparative example 4

Comparative example 5

Ratio of residue to residue

60.6％

43.3％

54.1％

73.2％

78.9％

20.4％

As can be seen from the data in table 1, the drug coating of the drug balloon prepared according to the present invention has good firmness and is not easy to fall off, while the drug coating of the drug balloon prepared according to comparative examples 1, 2, and 5 has poor firmness.

The method 2 comprises the following steps: the drug balloon prepared in the embodiment and the comparative example is placed into the coronary vessel mouth of a common white pig by PTCA forming, the balloon is placed for 5min under the state of not being pressed, then the balloon is withdrawn and recovered, the recovered balloon is placed in a sample bottle with a bottle cap, the sample is stored at low temperature until the sample is prepared by HPLC, the sample is taken out, the paclitaxel remained on the balloon is extracted by methanol and diluted according to a certain proportion, and the paclitaxel remained on the balloon is tested by HPLC. The higher the residual ratio, the higher the firmness of the surface drug-coated balloon. Table 2 lists all relevant experimental data.

TABLE 2

Example 1

Example 2

Example 3

Example 4

Example 5

Example 6

Ratio of residue to residue

60.4％

54.5％

56.9％

55.2％

57.4％

49.1％

Example 7

Comparative example 1

Comparative example 2

Comparative example 3

Comparative example 4

Comparative example 5

Ratio of residue to residue

38.6％

30.5％

14.6％

28.2％

36.7％

11.3％

As can be seen from the data in table 2, the balloons of examples 1, 2, 3, 4, 5, and 6 deliver drugs with high efficiency, while the balloons of example 7 and comparative examples 1, 2, 3, 4, and 5 deliver drugs with low efficiency, which is not ideal.

Compared with the prior art, the balloon surface is provided or coated with an elastic substance or an elastic emitting device (a layer directly contacting with the balloon), then is sequentially provided or coated with medicines and related auxiliary materials, and the outermost layer is a protective layer. The elastic substance or the elastic launching device is triggered by balloon expansion pressure induction, so that the medicine or the medicine particles are launched and embedded into the wall of the blood vessel, and the loss of the medicine is reduced. The preparation method is accurate, stable and efficient, and the prepared drug balloon has high delivery efficiency, firm combination of drug coatings and high drug utilization rate.

The foregoing detailed description of the preferred embodiments of the invention has been presented. It should be understood that numerous modifications and variations could be devised by those skilled in the art in light of the present teachings without departing from the inventive concepts. Therefore, the technical solutions available to those skilled in the art through logic analysis, reasoning and limited experiments based on the prior art according to the concept of the present invention should be within the scope of protection defined by the claims.

Claims

1. The preparation method of the medicine balloon is characterized by comprising the following steps:

2. The method of claim 1, wherein the elastic substance or device is collagen, latex, epoxy, rubber, microcoil, or metal microslip.

3. The method of claim 2, wherein in step (1), the elastomeric substance or device is cured to the surface of the balloon by light curing.

4. The method for preparing a drug balloon according to claim 1, wherein in the step (2), the drug solution is a solution containing an active drug and a carrier.

5. The method for preparing a drug balloon according to claim 4, wherein the active drug is selected from any one or a combination of at least two of rapamycin, a rapamycin derivative, or a paclitaxel drug.

6. The method of manufacturing a drug balloon according to claim 4, wherein the carrier contains amino groups and/or hydroxyl groups.

7. The method for preparing a drug balloon according to claim 1, wherein the surface solvation treatment of the step (3) is performed in an atmosphere of volatile organic solvent vapor.

8. The method for preparing a drug balloon according to claim 1, wherein the split folding process of the step (3) comprises: the saccule with medicine coating on the surface is pressed by a machine, is pressed and held by a chuck, is divided into 3 or 6 petals by pumping negative pressure, and is rolled and held by a scroll in a negative pressure state.

9. A drug balloon produced by the method of any one of claims 1-8.

10. Use of a drug balloon according to claim 9 as a device for treating in situ stenosis or restenosis within a blood vessel.