Preparation method of drug balloon and drug coating

Abstract

The invention discloses a preparation method of a drug balloon and a drug coating. A pressure dilation device of the drug balloon is connected with a balloon catheter, and the pressure dilation device is used for dilating the balloon catheter under the action of pressure, so that the balloon catheter is in contact with a blood vessel wall, and the contact pressure between the balloon catheter and the blood vessel wall is within a preset range; the drug coating is arranged on the balloon catheter, when the contact pressure is within a preset range and the drug coating is in a first pH environment, the drug coating is released from the surface of the balloon catheter, and the drug of the drug coating is conveyed to a preset part in the blood vessel wall. By means of the mode, the drug balloon can enable the drug coating to be rapidly released from the surface of the balloon catheter under the joint triggering action of the contact pressure within the preset range and the first pH environment, the delivery efficiency of drugs is effectively improved, and the concentration of the drugs in a preset part to be treated is improved.

Description

Technical Field

[0001] The present application relates to the field of medical device technology, and in particular to a method for preparing a drug balloon and a drug coating. Background Art

[0002] Cardiovascular disease is a common clinical disease. Drug-eluting balloons are commonly used medical devices for percutaneous coronary intervention (PCI). With the increasing use of drug-eluting balloons in recent years, drug-eluting balloons have made progress. When the expanded balloon catheter contacts the blood vessel wall, the drug on the surface of the balloon catheter is delivered to the lesion site to reduce the degree of vascular stenosis and reduce the formation of thrombosis in the stent.

[0003] Existing drug balloons have low drug delivery efficiency, and efficient drug delivery within the short surgical window remains a challenge. Summary of the invention

[0004] In order to solve the above technical problems, the present application provides a method for preparing a drug balloon and a drug coating.

[0005] To solve the above problems, the present application provides a first technical solution: a drug balloon is provided, comprising a balloon catheter, a pressure expansion device and a drug coating; the pressure expansion device is connected to the balloon catheter, and the pressure expansion device is used to expand the balloon catheter under pressure so that the balloon catheter contacts the blood vessel wall and the contact pressure between the balloon catheter and the blood vessel wall is within a preset range; the drug coating is arranged on the balloon catheter, and when the contact pressure is within the preset range and the drug coating is in a first pH environment, the drug coating is released from the surface of the balloon catheter, and the drug in the drug coating is delivered to a preset position in the blood vessel wall.

[0006] Optionally, the drug coating includes a first coating, the first coating includes a drug carrier and an inhibitory drug, the drug carrier is used to carry the inhibitory drug, and the drug carrier is also used to release the inhibitory drug so that the inhibitory drug combines with the vascular endothelium and inhibits restenosis of the blood vessel.

[0007] Optionally, the drug carrier is human serum albumin nanoparticles, the inhibitory drug is paclitaxel, and the drug carrier and the inhibitory drug are assembled under a second pH environment to form the first coating.

[0008] Optionally, the pH value of the second pH environment is lower than the pH value of the first pH environment, or the pH range of the first pH environment is 7.0-8.0, and the pH range of the second pH environment is 3.5-4.5.

[0009] Optionally, the first coating layer further includes heparin, and the heparin is coated on the drug carrier carrying the inhibitory drug under the second pH environment.

[0010] Optionally, the drug coating further comprises a second coating, the second coating is disposed on the balloon catheter, the first coating is stacked on the second coating, the second coating is located between the balloon catheter and the first coating, and the second coating is used to adhere the first coating to the balloon catheter.

[0011] Optionally, the second coating includes heparin and dopamine, the dopamine is coated on the surface of the balloon catheter, and the heparin is coated on the surface of the dopamine to form the second coating.

[0012] Optionally, the drug coating further includes a third coating, the first coating is located between the second coating and the third coating, the third coating is coated on the first coating, and the third coating is used to protect the first coating.

[0013] To solve the above problems, the present application provides a second technical solution: a method for preparing a drug coating, which is applied to the drug balloon as described above, the method comprising: obtaining a balloon catheter; immersing the balloon catheter in a dopamine solution and reacting for a first preset time to obtain the balloon catheter coated with dopamine; immersing the balloon catheter coated with dopamine in a heparin solution to obtain the balloon catheter with a first coating; mixing and emulsifying human serum albumin and a paclitaxel solution to obtain a human serum albumin nanoparticle solution loaded with paclitaxel; immersing the balloon catheter with the first coating in the human serum albumin nanoparticle solution loaded with paclitaxel and the heparin solution in turn to perform multi-layer coating and obtain the balloon catheter with a second coating; coating the balloon catheter with the second coating with a shellac solution to obtain the balloon catheter with a third coating.

[0014] Optionally, the immersing the balloon catheter in a dopamine solution and reacting for a first preset time to obtain the balloon catheter coated with dopamine comprises: immersing the balloon catheter in a buffer solution with a pH value of 8.5, adding the dopamine solution to the buffer solution with a pH value of 8.5, and reacting for a first preset time to obtain the balloon catheter coated with dopamine; and / or, the mixing and emulsifying human serum albumin with a paclitaxel solution to obtain a human serum albumin nanoparticle solution loaded with paclitaxel comprises: respectively adding the human serum albumin and the paclitaxel solution to a buffer solution with a pH value of 4.0; mixing the human serum albumin with the paclitaxel solution, and emulsifying to obtain a human serum albumin nanoparticle solution loaded with paclitaxel.

[0015] The present application provides a preparation method of a drug balloon and a drug coating, wherein a pressure expansion device of the drug balloon is connected to a balloon catheter, and the pressure expansion device is used to expand the balloon catheter under pressure, so that the balloon catheter contacts the blood vessel wall and the contact pressure between the balloon catheter and the blood vessel wall is within a preset range; the drug coating is disposed on the balloon catheter, and when the contact pressure is within a preset range and the drug coating is in a first pH environment, the drug coating is released from the surface of the balloon catheter, and the drug in the drug coating is delivered to a preset position in the blood vessel wall. In the above manner, the drug balloon can be triggered by the contact pressure within the preset range and the first pH environment, so that the drug coating can be quickly released from the surface of the balloon catheter, effectively improving the delivery efficiency of the drug and increasing the concentration of the drug in the preset position to be treated. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work. Among them:

[0017] Figure 1 is a schematic structural diagram of the first embodiment of the drug balloon provided by the present application;

[0018] Figure 2 is a schematic structural diagram of a second embodiment of a drug balloon provided by the present application;

[0019] Figure 3 It is a schematic flow chart of a first embodiment of a method for preparing a drug coating provided by the present application;

[0020] Figure 4 It is a schematic flow chart of a second embodiment of the method for preparing a drug coating provided by the present application;

[0021] Figure 5 is a schematic diagram of the total fluorescence of human serum albumin particles at different pH values ​​provided by the present application;

[0022] Figure 6 is a schematic diagram of the release amount of paclitaxel at different pH values ​​provided in the present application;

[0023] Figure 7 It is a schematic diagram of the release efficiency of the balloon catheter provided in the present application at different pressure values.

[0024] In the figure, 10, drug balloon; 11, balloon catheter; 12, pressure expansion device; 13, drug coating; 131, first coating; 132, second coating; 133, third coating; 20, blood vessel wall. DETAILED DESCRIPTION

[0025] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0026] It should be noted that if the embodiments of the present application involve directional indications (such as up, down, left, right, front, back...), the directional indications are only used to explain the relative position relationship, movement status, etc. between the components under a certain specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indication will also change accordingly.

[0027] In addition, if there are descriptions involving "first", "second", etc. in the embodiments of the present application, the descriptions of "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or suggesting their relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In addition, the technical solutions between the various embodiments can be combined with each other, but they must be based on the ability of ordinary technicians in the field to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such combination of technical solutions does not exist and is not within the scope of protection required by this application.

[0028] In order to solve the above technical problems, the embodiment of the present application first provides a drug balloon, which can be an instrument for interventional treatment, especially percutaneous coronary intervention (PCI). The balloon catheter of the drug balloon is used to mechanically dilate the stenotic part of the blood vessel, and the drug coating of the drug balloon can be used to reduce the possibility of restenosis of the blood vessel. The drug balloon of the embodiment of the present application can significantly improve the efficiency of the drug coating released from the surface of the balloon catheter, improve the practicality and reliability of the drug balloon in the field of medical devices for interventional treatment, and is conducive to the further development of the drug balloon.

[0029] See also Figure 1 , Figure 1 Schematic diagram of the structure of the first embodiment of the drug balloon provided by the present application. Figure 1 As shown, the drug balloon 10 of this embodiment includes a balloon catheter 11 , a pressure expansion device 12 and a drug coating 13 .

[0030] Specifically, the pressure expansion device 12 is connected to the balloon catheter 11, and the pressure expansion device 12 is used to expand the balloon catheter 11 under pressure so that the balloon catheter 11 contacts the blood vessel wall 20 and the contact pressure between the balloon catheter 11 and the blood vessel wall 20 is within a preset range; the drug coating 13 is arranged on the balloon catheter 11, and when the contact pressure is within the preset range and the drug coating 13 is in a first pH environment, the drug coating 13 is released from the surface of the balloon catheter 11, and the drug in the drug coating 13 is delivered to a preset position in the blood vessel wall 20.

[0031] Specifically, the balloon catheter 11 may include a catheter body and an expansion part, and the pressure expansion device 12 is connected to the catheter body or the expansion part of the balloon catheter 11 so that the expansion part expands or contracts relative to the catheter body. The drug coating 13 is arranged on the surface of the expansion part of the balloon catheter 11. When the drug balloon 10 is placed at the treatment site or the lesion site, the pressure expansion device 12 expands the balloon catheter 11, and the surface of the expansion part moves outward until the balloon catheter 11 contacts the blood vessel wall 20 and the contact pressure between the balloon catheter 11 and the blood vessel wall 20 is within a preset range, the drug coating 13 contacts the surface of the blood vessel wall 20, or the drug coating 13 contacts the blood on the blood vessel wall 20, so that the drug coating 13 is in a first pH environment. At this time, the drug coating 13 is released from the surface of the balloon catheter 11, and the drug in the drug coating 13 is delivered to the preset position in the blood vessel wall 20.

[0032] In a possible embodiment, the drug coating 13 may also be released from the surface of the balloon catheter 11 in other pH environments and / or under contact pressures outside the preset range. Wherein, when the contact pressure is within the preset range and the drug coating 13 is in a first pH environment, the rate at which the drug coating 13 is released from the surface of the balloon catheter 11 may be defined as a first rate; the rate at which the drug coating 13 is released from the surface of the balloon catheter 11 in other pH environments and / or under contact pressures outside the preset range is defined as a second rate, and the first rate is greater than the second rate. Alternatively, when the contact pressure is within the preset range and the drug coating 13 is in the first pH environment, the amount of the drug coating 13 released from the surface of the balloon catheter 11 is defined as a first value; the amount of the drug coating 13 released from the surface of the balloon catheter 11 in other pH environments and / or under contact pressures outside the preset range is a second value, and the first value is greater than the second value.

[0033] Among them, the preset range of contact pressure can be the contact pressure range that can be achieved while minimizing the risk of vascular damage caused by excessive expansion of the blood vessel under the premise of ensuring the effective fit between the balloon catheter 11 and the blood vessel wall 20. The preset range of contact pressure can also be adjusted based on the treatment site, means, etc., and is not specifically limited here. The first pH environment is usually the physiological pH when the patient maintains normal metabolism and physiological functions in the body; or, the first pH environment can float up and down within the physiological pH range, for example, the range of the first pH environment is slightly larger than the physiological pH range; or, the first pH environment is the pH range when the release amount or release rate of the drug coating 13 from the surface of the balloon catheter 11 is greater than a preset threshold. The first pH environment can also be adjusted based on the different patients, treatment sites or means, and is not specifically limited here.

[0034] In the embodiment of the present application, the pressure expansion device 12 of the drug balloon 10 is connected to the balloon catheter 11, and the pressure expansion device 12 is used to expand the balloon catheter 11 under pressure, so that the balloon catheter 11 contacts the blood vessel wall 20 and the contact pressure between the balloon catheter 11 and the blood vessel wall 20 is within a preset range; the drug coating 13 is provided on the balloon catheter 11, and when the contact pressure is within the preset range and the drug coating 13 is in a first pH environment, the drug coating 13 is released from the surface of the balloon catheter 11, and the drug in the drug coating 13 is delivered to the preset position in the blood vessel wall 20. In the above manner, the drug balloon 10 can be triggered by the contact pressure within the preset range and the first pH environment, so that the drug coating 13 can be quickly released from the surface of the balloon catheter 11, effectively improving the delivery efficiency of the drug and increasing the concentration of the drug in the preset position to be treated.

[0035] In one embodiment, see Figure 2 , Figure 2 Schematic diagram of the structure of the second embodiment of the drug balloon 10 provided by the present application. Figure 2 As shown, the drug coating 13 includes a first coating 131, and the first coating 131 includes a drug carrier and an inhibitory drug. The drug carrier is used to carry the inhibitory drug, and the drug carrier is also used to release the inhibitory drug so that the inhibitory drug is combined with the vascular endothelium and inhibits vascular restenosis.

[0036] Specifically, the first coating 131 includes a drug carrier and an inhibitory drug, wherein the drug carrier is used to carry the inhibitory drug, and the inhibitory drug is used to combine with the vascular endothelium and inhibit vascular restenosis, and the inhibitory drug includes but is not limited to paclitaxel, sirolimus, dexamethasone, nitroglycerin, metalloproteinase inhibitors, immunomodulators, and other drugs used to inhibit or reduce vascular restenosis. The drug carrier includes but is not limited to polymer-based carriers, liposomes, nanoparticles, oil-water mixtures, hydrogels, chitosan, and the like.

[0037] It can be understood that the first coating 131 of this embodiment is a composite drug coating 13, and the drug carrier in the first coating 131 is used to stably deposit on the surface of the balloon catheter 11 at a pH value other than the first pH environment, and detach from the surface of the balloon catheter 11 under the first pH environment, so that the inhibitory drug carried by the drug carrier can be delivered to a preset site. In this way, the drug balloon 10 of this embodiment can achieve efficient and rapid delivery of inhibitory drugs, and enable the inhibitory drugs to be accurately delivered to the preset lesion site, thereby increasing the concentration of the inhibitory drugs at the lesion site and reducing the loss of the inhibitory drugs during the delivery process.

[0038] Optionally, the drug carrier is human serum albumin nanoparticles, the inhibitory drug is paclitaxel, and the drug carrier and the inhibitory drug are assembled under a second pH environment to form the first coating 131 .

[0039] Specifically, the second pH environment is a pH range outside the first pH environment. When the drug carrier is human serum albumin nanoparticles, since human serum albumin nanoparticles have the characteristic of charge reversal, in the second pH environment, the human serum albumin nanoparticles are located near the isoelectric point, and the albumin charge of the human serum albumin nanoparticles is reversed to present a positive charge, so that the drug carrier carrying the inhibitory drug can be stably deposited on the surface of the balloon catheter 11 and form the first coating 131. In the first pH environment, the human serum albumin nanoparticles present a negative charge, so that the drug carrier carrying the inhibitory drug can be detached from the surface of the balloon catheter 11.

[0040] Therefore, in the drug coating 13 of this embodiment, under the first pH environment, the first coating 131 can be quickly released from the surface of the balloon catheter 11, and the human serum albumin nanoparticles can quickly deliver paclitaxel to the preset lesion site, thereby increasing the concentration of the inhibitory drug at the lesion site and reducing the loss of the inhibitory drug during the delivery process.

[0041] Further, the pH value of the second pH environment is lower than the pH value of the first pH environment, or the pH range of the first pH environment is 7.0-8.0, and the pH range of the second pH environment is 3.5-4.5.

[0042] Specifically, in one embodiment, the pH value of the second pH environment is lower than the pH value of the first pH environment, and the second pH environment or the first pH environment is located near the isoelectric point of the human serum albumin nanoparticles, so that the charge properties of the human serum albumin nanoparticles in the second pH environment and the first pH environment are different, thereby allowing the human serum albumin nanoparticles loaded with paclitaxel to be stably deposited on the surface of the balloon catheter 11 due to the charge effect in one pH environment, and to detach from the surface of the balloon catheter 11 due to charge reversal in the other pH environment.

[0043] In another embodiment, the pH range of the first pH environment is 7.0-8.0, and the pH value of the first pH environment can be 7.0, 7.2, 7.4, 7.6, 7.8 or 8.0. The pH range of the second pH environment is 3.5-4.5, and the pH range of the second pH environment is 3.5-4.5, and the pH value of the second pH environment can be 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4 or 4.5.

[0044] Through the above method, the first coating 131 of the present embodiment can be accurately positioned to release the drug when in the first pH environment, thereby increasing the concentration of the inhibitory drug at the lesion site and reducing the loss of the inhibitory drug during the delivery process.

[0045] Furthermore, the first coating layer 131 further includes heparin, and the heparin is coated on the drug carrier carrying the inhibitory drug under the second pH environment.

[0046] Specifically, heparin has a high negative charge density and can interact with positively charged substances. Under the second pH environment, after the inhibitory drug is assembled with the drug carrier, the drug carrier carrying the inhibitory drug can form a positive charge layer and attract each other with the negative charge of heparin, so that heparin interacts and fixes with the drug carrier carrying the inhibitory drug to stabilize the inhibitory drug. When the first coating 131 is in the first pH environment, due to the charge reversal of the human serum albumin nanoparticles, the drug carrier carrying the inhibitory drug forms a negative charge layer, so that heparin and the drug carrier carrying the inhibitory drug repel each other, and the drug carrier carrying the inhibitory drug is quickly released from the balloon surface, effectively improving the delivery efficiency of the inhibitory drug.

[0047] Optionally, the drug coating 13 further includes a second coating 132 , which is disposed on the balloon catheter 11 , and the first coating 131 is stacked on the second coating 132 , and the second coating 132 is located between the balloon catheter 11 and the first coating 131 , and the second coating 132 is used to adhere the first coating 131 to the balloon catheter 11 .

[0048] Specifically, the second coating 132 can be applied to the substrate of the balloon catheter 11. The second coating 132 can form structures such as cross-linked polymers, network polymers, branched polymers, polymer nanomaterials, and layered polymers, so that the second coating 132 can stably adhere to the surface of the balloon catheter 11, thereby improving the mechanical stability of the second coating 132 when connected to the balloon catheter 11, so that the first coating 131 can be subsequently adhered to the second coating 132 and chemically connected to the second coating 132, thereby reducing or avoiding the loss of inhibitory drugs in the first coating 131 due to the direct mechanical connection of the first coating 131 to the balloon catheter 11, and improving the safety and stability of the first coating 131 before the expected release.

[0049] Furthermore, the second coating 132 includes heparin and dopamine. Dopamine is coated on the surface of the balloon catheter 11 , and heparin is coated on the surface of dopamine to form the second coating 132 .

[0050] Specifically, the dopamine of the second coating 132 is directly coated on the surface of the balloon catheter 11 to form a dopamine layer. Heparin is coated on the surface of the dopamine. Since heparin usually contains amines and is negatively charged, heparin can be stably deposited on the dopamine layer and form a cross-linked polymer network. At the same time, since heparin is negatively charged, when the drug carrier is human serum albumin nanoparticles and the inhibitory drug is paclitaxel, the drug carrier with a positive charge can attract heparin through electrostatic action, so that the first coating 131 can adhere to the second coating 132. In the above manner, the drug coating 13 of this embodiment realizes the connection between the first coating 131 and the balloon catheter 11 through the second coating 132, which can reduce or avoid the loss of the inhibitory drug of the first coating 131 caused by the direct mechanical connection of the first coating 131 with the balloon catheter 11, and improve the safety and stability of the first coating 131 before the expected release.

[0051] Furthermore, the drug coating 13 also includes a third coating 133 . The first coating 131 is located between the second coating 132 and the third coating 133 . The third coating 133 is coated on the first coating 131 . The third coating 133 is used to protect the first coating 131 .

[0052] Specifically, the third coating 133 includes but is not limited to a shellac layer. The third coating 133 is applied on the first coating 131 to protect the first coating 131 as a barrier to reduce or avoid drug diffusion caused by blood flow before the drug balloon 10 reaches the operating position, which can effectively reduce and inhibit drug loss.

[0053] The present application also provides a method for preparing a drug coating 13, which is applied to the drug balloon 10 of any of the above embodiments, and is specifically used to prepare the drug coating 13 of any of the above embodiments. Figure 3 , Figure 3 FIG. 1 is a schematic flow chart of a first embodiment of a method for preparing a drug coating provided by the present application. Figure 3 As shown, in this embodiment, the preparation method includes the following steps:

[0054] Step S11: Obtain a balloon catheter 11.

[0055] Specifically, the balloon catheter 11 can be used for dilation of coronary arteries, and can also be used in other fields such as tumors, gastrointestinal and urinary systems. The cleanliness and strength of the obtained balloon catheter 11 meet the requirements of actual application scenarios.

[0056] Step S12: immersing the balloon catheter 11 in the dopamine solution and reacting for a first preset time to obtain the balloon catheter 11 coated with dopamine.

[0057] After obtaining the balloon catheter 11, the balloon catheter 11 is immersed in a dopamine solution and reacted for a first preset time. After the reaction, the balloon catheter 11 is taken out of the dopamine solution and washed multiple times with a physiological buffer solution to reduce or avoid deposition or aggregation of dopamine particles loosely attached to the surface, and a balloon catheter 11 coated with dopamine is obtained.

[0058] Step S13 : immersing the balloon catheter 11 coated with dopamine in a heparin solution to obtain the balloon catheter 11 with the first coating 131 formed thereon.

[0059] After obtaining the dopamine-coated balloon catheter 11, the dopamine-coated balloon catheter 11 can be immersed in a heparin solution for reaction. After the reaction, the balloon catheter 11 is taken out of the heparin solution and washed multiple times with a physiological buffer solution to reduce or avoid the deposition or aggregation of heparin particles loosely attached to the surface, and the balloon catheter 11 with the first coating 131 is obtained.

[0060] Step S14: mixing and emulsifying human serum albumin and paclitaxel solution to obtain a paclitaxel-loaded human serum albumin nanoparticle solution.

[0061] Specifically, after human serum albumin and paclitaxel solution are mixed, a homogenizer can be used to emulsify the mixed human serum albumin and paclitaxel solution. After the emulsification operation, the emulsified human serum albumin and paclitaxel solution are stabilized at 50° C. for a second preset time, and purified by dialysis to obtain a human serum albumin nanoparticle solution loaded with paclitaxel.

[0062] Step S15 : sequentially immersing the balloon catheter 11 having the first coating 131 formed thereon into a human serum albumin nanoparticle solution loaded with paclitaxel and a heparin solution to perform multi-layer coating and obtain the balloon catheter 11 having the second coating 132 formed thereon.

[0063] Specifically, after obtaining the human serum albumin nanoparticle solution loaded with paclitaxel, the balloon catheter 11 with the first coating 131 is immersed in the human serum albumin nanoparticle solution loaded with paclitaxel and the heparin solution in sequence. Specifically, the balloon catheter 11 with the first coating 131 is immersed in the human serum albumin nanoparticle solution loaded with paclitaxel and reacted for a third preset time, and then washed multiple times with a physiological buffer solution; then the balloon catheter 11 is taken out, immersed in the heparin solution, reacted for a fifth preset time, and then washed multiple times with a physiological buffer solution.

[0064] The multi-layer coating can be understood as repeating the above operation, and washing multiple times with a physiological buffer solution after each coating operation, so that the first coating 131 includes multiple layers of functional coatings composed of human serum albumin nanoparticles loaded with paclitaxel and heparin, and the balloon catheter 11 forming the second coating 132 is obtained. The multi-layer coating can include two or more layers of functional coatings composed of human serum albumin nanoparticles loaded with paclitaxel and heparin, which is not specifically limited here.

[0065] Step S16 : coating the balloon catheter 11 with the second coating layer 132 using a shellac solution to obtain the balloon catheter 11 with the third coating layer 133 .

[0066] After the balloon catheter 11 with the second coating layer 132 is obtained, the balloon catheter 11 with the second coating layer 132 is coated with a shellac solution and dried to form a protective outer layer, so as to obtain the balloon catheter 11 with the third coating layer 133 .

[0067] Furthermore, the physiological buffer solution used above can be a relevant buffer solution that simulates the blood environment, and the physiological buffer solution includes but is not limited to a phosphate buffered saline (PBS) having a pH value of about 7.4. When the physiological buffer solution is used for multiple flushing, the flushing times of the physiological buffer solution can be ensured by limiting the flushing time of the physiological buffer solution, which is not specifically limited here.

[0068] In the above manner, the preparation method of this embodiment can prepare a balloon catheter 11 including a second coating 132, a first coating 131 and a third coating 133 from the inside to the outside. The third coating 133 protects the first coating 131 to reduce or avoid drug diffusion caused by blood flow before the drug balloon 10 reaches the operating position; the second coating 132 is used to connect the first coating 131 and the balloon catheter 11, reducing or avoiding the loss of inhibited drugs in the first coating 131 caused by directly mechanically connecting the first coating 131 to the balloon catheter 11; through the third coating 133 and the second coating 132, the safety and stability of the first coating 131 before the expected release can be effectively improved, and the accurate release of the first coating 131 can be ensured, so as to improve the release efficiency and release amount of the drug coating 13 from the surface of the balloon catheter 11.

[0069] In one embodiment, step S12 includes: immersing the balloon catheter 11 in a buffer solution with a pH value of 8.5, and adding a dopamine solution to the buffer solution with a pH value of 8.5, and reacting for a first preset time to obtain a balloon catheter 11 coated with dopamine.

[0070] The buffer with a pH value of 8.5 may be, but is not limited to, a PBS buffer with a pH value of 8.5. When preparing the balloon catheter 11 coated with dopamine, setting the pH value to 8.5 can provide a stable oxidation environment for dopamine, so as to facilitate the oxidation cross-linking between dopamine and heparin.

[0071] In one embodiment, step S14 comprises: adding human serum albumin and paclitaxel solution to a buffer solution with a pH value of 4.0 respectively; mixing the human serum albumin and the paclitaxel solution, and emulsifying them to obtain a human serum albumin nanoparticle solution loaded with paclitaxel.

[0072] Specifically, in this embodiment, the pH value corresponding to the second pH environment is 4.0, and the buffer solution with a pH value of 4.0 may be, but is not limited to, a PBS buffer solution with a pH value of 4.0. When preparing a paclitaxel-loaded human serum albumin nanoparticle solution, the pH value is set to 4.0, so that the stability of the paclitaxel-loaded human serum albumin nanoparticle solution prepared under the pH environment is better, and the paclitaxel-loaded human serum albumin nanoparticles are positively charged under a pH value of 4.0, and can be fixed to each other by electrostatic action when reacting with heparin molecules later to form a stable deposition layer.

[0073] In one embodiment, the first preset time is 4 hours, and the second preset time is 5 hours.

[0074] See also Figure 4 , Figure 4 FIG. 2 is a flow chart of a second embodiment of the method for preparing a drug coating provided by the present application. Figure 4 As shown, in this embodiment, the preparation method includes the following steps:

[0075] Step S21: human serum albumin and paclitaxel solution are respectively added to a buffer solution with a pH value of 4.0, the human serum albumin and paclitaxel solution are mixed, and the mixed human serum albumin and paclitaxel solution are emulsified using a homogenizer, and the emulsified human serum albumin and paclitaxel solution is stabilized at 50° C. for 5 hours and purified by dialysis to obtain a human serum albumin nanoparticle solution loaded with paclitaxel.

[0076] Step S22: immersing the balloon catheter 11 in a buffer solution with a pH value of 8.5, and adding the dopamine solution into the buffer solution with a pH value of 8.5, reacting for 4 hours, and then washing the solution multiple times with a physiological buffer solution to obtain a balloon catheter 11 coated with dopamine.

[0077] Step S23 : immersing the balloon catheter 11 coated with dopamine in a heparin solution, and washing it multiple times with a physiological buffer solution to obtain the balloon catheter 11 with the first coating 131 formed thereon.

[0078] Step S24 : sequentially immersing the balloon catheter 11 having the first coating 131 formed thereon into a human serum albumin nanoparticle solution loaded with paclitaxel and a heparin solution to perform multi-layer coating and obtain the balloon catheter 11 having the second coating 132 formed thereon.

[0079] Step S25 : sequentially immersing the balloon catheter 11 with the second coating 132 formed thereon into a shellac solution with a concentration of 1%-9% to obtain the balloon catheter 11 with the third coating 133 formed thereon.

[0080] In one embodiment, after the balloon catheter 11 coated with the drug coating 13 is obtained by the preparation method of the first embodiment or the second embodiment described above, an in vitro drug release test can be performed on the balloon catheter 11 including the drug coating 13 to determine the stability and release characteristics of the drug coating 13.

[0081] Specifically, see Figure 5 and Figure 6 , Figure 5 is a schematic diagram of the total fluorescence of human serum albumin particles at different pH values ​​provided in this application, Figure 6 The present application provides a schematic diagram of the release amount of paclitaxel at different pH values. The balloon catheter 11 including the drug coating 13 is placed in a phosphate buffer with different pH values ​​to observe the drug release. The human serum albumin particles can be labeled with a fluorescent substance, and the total amount of fluorescence remaining in the balloon catheter 11 at different time points can be measured using a related fluorescence imaging device to obtain Figure 5At the same time point as the fluorescence measurement, high performance liquid chromatography (HPLC) was used to quantitatively analyze the release amount of paclitaxel at different pH values ​​to obtain Figure 6 .

[0082] like Figure 5 As shown, the drug coating 13 of the balloon catheter 11 is in phosphate buffers with pH values ​​of 4.0, 5.0, 6.0, 7.0 and 7.4, respectively. When the balloon catheter 11 is left at rest for 180 seconds under the conditions of pH values ​​of 4.0, 5.0 and 6.0, the total fluorescence of the balloon catheter 11 changes slightly; when the balloon catheter 11 is left at rest for 180 seconds under the conditions of pH values ​​of 7.0 and 7.4, the total fluorescence of the balloon catheter 11 changes greatly, and the total fluorescence at pH value of 7.4 can drop rapidly within 30 seconds and gradually return to 0 at 120 seconds. Therefore, the human serum albumin particles on the balloon catheter 11 can be quickly released from the surface of the balloon catheter 11 under the action of pressure under the first pH environment.

[0083] like Figure 6 As shown, in Figure 5 Under the corresponding pH environment and experimental conditions, at pH 4.0 and 5.0, the content of paclitaxel released in the solution barely reached 0.1 μg / mm after 250 s. 2 At pH 6.0, the content of paclitaxel released in the solution can reach 0.25 μg / mm after 250 s. 2 Under the conditions of pH values ​​of 7.0 and 7.4, the release amount of paclitaxel varies greatly, and the release amount of paclitaxel at pH value of 7.4 can be rapidly increased within 100 seconds and reach about 0.45 at 250 seconds. Therefore, the paclitaxel on the balloon catheter 11 can be released and dissolved from the surface of the balloon catheter 11 under the first pH environment, and the release efficiency of paclitaxel is as high as 96.3%.

[0084] For further information, see Figure 7 , Figure 7 Schematic diagram of the release efficiency of the balloon catheter provided by the present application at different pressure values. Figure 7 As shown, the balloon catheter 11 including the drug coating 13 can also be placed in an environment with different pressures, for example, human serum albumin particles can be marked with a fluorescent substance to obtain the total fluorescence of the fluorescent substance. Figure 7 .like Figure 7 As shown, under different pressure values, the efficiency of drug release from the surface of the balloon catheter 11 increases with the increase of pressure value. When the pressure value reaches 4 atm, the efficiency of drug release can reach 100%.

[0085] Therefore, different from the prior art, the drug balloon 10 of the embodiment of the present application can significantly increase the amount of drug delivered to the target tissue, and achieves accurate controlled release of high-dose paclitaxel, which can make the paclitaxel release amount reach 400 micrograms per gram of tissue. Therefore, the drug balloon 10 of this embodiment has excellent drug release efficiency, which is expected to improve the treatment effect of PCI and reduce the risk of restenosis and stent thrombosis.

[0086] The above description is only an implementation method of the present application, and does not limit the patent scope of the present application. Any equivalent structure or equivalent process transformation made using the contents of the present application specification and drawings, or directly or indirectly used in other related technical fields, are also included in the patent protection scope of the present application.

Claims

1. A drug balloon, characterized in that: include: Balloon catheters; a pressure expansion device connected to the balloon catheter, the pressure expansion device being used to expand the balloon catheter under pressure so that the balloon catheter contacts the blood vessel wall and the contact pressure between the balloon catheter and the blood vessel wall is within a preset range; The drug coating is arranged on the balloon catheter. When the contact pressure is within a preset range and the drug coating is in a first pH environment, the drug coating is released from the surface of the balloon catheter, and the drug in the drug coating is delivered to a preset position in the blood vessel wall.

2. The drug balloon according to claim 1, characterized in that: The drug coating comprises a first coating, wherein the first coating comprises a drug carrier and an inhibitory drug, wherein the drug carrier is used to carry the inhibitory drug and release the inhibitory drug so that the inhibitory drug is combined with the vascular endothelium and inhibits restenosis of the blood vessel.

3. The drug balloon according to claim 2, characterized in that: The drug carrier is human serum albumin nanoparticles, the inhibitory drug is paclitaxel, and the drug carrier and the inhibitory drug are used to assemble in a second pH environment to form the first coating.

4. The drug balloon according to claim 3, characterized in that: The pH value of the second pH environment is lower than the pH value of the first pH environment, or the pH range of the first pH environment is 7.0-8.0, and the pH range of the second pH environment is 3.5-4.

5.

5. The drug balloon according to claim 3, characterized in that: The first coating layer further includes heparin, and the heparin is coated on the drug carrier carrying the inhibitory drug under the second pH environment.

6. The drug balloon according to claim 2, characterized in that: The drug coating also includes a second coating, which is disposed on the balloon catheter, the first coating is stacked on the second coating, the second coating is located between the balloon catheter and the first coating, and the second coating is used to adhere the first coating to the balloon catheter.

7. The drug balloon according to claim 6, characterized in that: The second coating layer includes heparin and dopamine. The dopamine is coated on the surface of the balloon catheter, and the heparin is coated on the surface of the dopamine to form the second coating layer.

8. The drug balloon according to claim 6, characterized in that: The drug coating also includes a third coating, the first coating is located between the second coating and the third coating, the third coating is coated on the first coating, and the third coating is used to protect the first coating.

9. A method for preparing a drug coating, characterized in that: Applicable to the drug balloon according to any one of claims 1 to 8, the preparation method comprising: Obtain a balloon catheter; Immersing the balloon catheter in a dopamine solution and reacting for a first preset time to obtain the balloon catheter coated with dopamine; immersing the dopamine-coated balloon catheter in a heparin solution to obtain the balloon catheter with a first coating formed thereon; mixing and emulsifying human serum albumin and paclitaxel solution to obtain a paclitaxel-loaded human serum albumin nanoparticle solution; Sequentially immersing the balloon catheter formed with the first coating into the human serum albumin nanoparticle solution loaded with paclitaxel and the heparin solution to perform multi-layer coating and obtain the balloon catheter formed with the second coating; The balloon catheter having the second coating layer formed thereon is coated with a shellac solution to obtain the balloon catheter having the third coating layer formed thereon.

10. The preparation method according to claim 9, characterized in that: The step of immersing the balloon catheter in a dopamine solution and reacting for a first preset time to obtain the balloon catheter coated with dopamine comprises: Immersing the balloon catheter in a buffer solution with a pH value of 8.5, and adding the dopamine solution to the buffer solution with a pH value of 8.5, and reacting for the first preset time to obtain the balloon catheter coated with dopamine; and / or, The method of mixing and emulsifying human serum albumin and paclitaxel solution to obtain a paclitaxel-loaded human serum albumin nanoparticle solution comprises: Adding the human serum albumin and the paclitaxel solution to a buffer solution with a pH value of 4.0 respectively; The human serum albumin is mixed with the paclitaxel solution and emulsified to obtain the paclitaxel-loaded human serum albumin nanoparticle solution.

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