CN117159889A - drug balloon catheter - Google Patents

Abstract

The invention discloses a drug balloon catheter, which includes a catheter, a balloon, a cutting element, a pressurizing device, a first electrode and a voltage control device. The balloon is arranged at the distal end of the catheter, and the balloon is connected to the pressurizing device through a channel. The channel is arranged in the catheter; the cutting element is arranged on the surface of the balloon; the surface of the balloon and/or the surface of the cutting element is provided with a drug coating; the first electrode is arranged on the outside of the distal end of the catheter and inside the balloon, and the voltage The control device is located at the proximal end of the catheter; the first electrode is electrically connected to the first conductive end of the voltage control device through the first wire, and the cutting element serves as the second electrode and is electrically connected to the second conductive end of the voltage control device through the second wire; The first conductive end and the second conductive end have opposite polarities; the first conductor and the second conductor are arranged in the conduit. The drug balloon catheter of the present invention can increase the drug release rate of the balloon, improve the drug absorption rate of the tissue, and improve the therapeutic effect.

Description

drug balloon catheter

Technical field

The present invention relates to a drug balloon catheter, and in particular to a drug balloon catheter that can increase the drug release rate of the balloon and increase the drug absorption rate of the tissue.

Background technique

Drug-coated balloon catheter (balloon catheter for short) refers to a balloon catheter in which a drug coating is loaded on the surface of an ordinary bare balloon. After the drug-laden balloon is delivered to the lesion, the balloon expands to cause the lesion to The blood vessel wall is restored to smoothness, and at the same time, the drug coating is eluted from the balloon surface and released to the blood vessel wall, which can further inhibit the proliferation of smooth muscle cells and prevent blood vessel restenosis. Therefore, drug-coated balloon catheters can not only establish channels for blood vessels through balloon dilation, but also avoid defects such as stent restenosis and thrombosis after stent implantation.

However, prior art drug-coated balloon catheters have the following problems: Since the contact time between the surface of the drug-coated balloon catheter and the vessel wall is very short, for coronary arteries, the balloon may only be inflated for less than one minute, and usually The expansion time is only thirty seconds, for peripheral vasculature, the allowable expansion time may be greater than one minute, but is still measured in minutes. Therefore, due to the short expansion time required, the time for drug or coating transfer is also short. Therefore, a large amount of drug will remain in the balloon, affecting the drug transfer rate, resulting in a low drug absorption rate, thereby affecting the therapeutic effect.

Especially for severe calcified lesions, the immediate lumen acquisition is low, the rebound is severe, and the drug absorption rate is low, which affects the prognosis of drug-coated balloons. There are no disclosed solutions for prior art drug-coated balloon catheters.

Contents of the invention

The object of the present invention is to provide a drug balloon catheter that can increase the drug release rate of the balloon and improve the drug absorption rate of the tissue.

In order to achieve the above object, the drug balloon catheter provided by the present invention includes a catheter, a balloon, a cutting element, a pressurizing device, a first electrode and a voltage control device. The balloon is arranged at the distal end of the catheter, and the balloon The balloon is connected to the pressurizing device through a channel, and the channel is arranged in the catheter; the cutting element is arranged on the surface of the balloon; the surface of the balloon and/or the surface of the cutting element is arranged on There is a drug coating; the first electrode is arranged outside the distal end of the catheter and inside the balloon, and the voltage control device is located at the proximal end of the catheter; the first electrode passes through a first wire Electrically connected to the first conductive end of the voltage control device, the cutting element serves as a second electrode and is electrically connected to the second conductive end of the voltage control device through a second wire; the first conductive end is connected to the second conductive end of the voltage control device. The polarity of the conductive end is opposite. When the voltage control device applies a high voltage pulse to the cutting element and the first electrode, radio frequency energy can be generated between the cutting element and the first electrode; the first conductor and a second wire is disposed in the conduit.

Compared with the prior art, the present invention sets a balloon at the distal end of the catheter so that the balloon communicates with the inflation device through a channel. Therefore, the inflation device can be used to control the contraction and expansion of the balloon. This allows the balloon to dilate blood vessels and release drugs coated on the surface near the lesion. By arranging a cutting element on the surface of the balloon, the contraction and expansion of the balloon can drive the cutting element to score or cut the diseased tissue, so that the medicine can penetrate deeper into the diseased tissue more quickly. It can not only increase the drug release rate of the balloon, but also increase the drug absorption rate of the tissue, thereby improving the therapeutic effect. In addition, by electrically connecting the first electrode and the cutting element to the voltage control device, the voltage control device is used to adjust the voltage to a certain value, so that the first electrode can emit light to the cutting element. Radiofrequency energy can promote the release of drugs, and the radiofrequency energy transmitted to the lesion of the blood vessel can cause vasodilation and change the permeability of cells; and, by regulating the radiofrequency signal, the drug can be delivered deeper into the blood vessel wall, allowing The drug remains within the vessel wall longer and improves drug durability within the vasculature, thereby enhancing drug delivery and increasing tissue absorption.

Preferably, the pulse width of the high voltage pulse is between about 0.08 microseconds and about 600 microseconds.

Preferably, the radio frequency energy voltage is between 400V and 4000V.

Preferably, the drug balloon catheter further includes an ultrasonic generator and an ultrasonic control device. The ultrasonic generator is arranged inside the balloon; the ultrasonic generator is electrically connected to the ultrasonic control device through a third wire. ; The third wire is arranged in the conduit. The ultrasonic energy is generated by the ultrasonic generator. After the ultrasonic energy is transmitted to the cutting element, the cutting element has stronger cutting ability and improves the cutting ability of the cutting element to score the diseased component. At the same time, the ultrasonic wave is transmitted to the blood vessel wall through the cutting element, which can effectively treat the diseased tissue. Impact can effectively treat moderately and severely calcified diseased tissue; due to the improvement of the scoring ability of the cutting element, combined with the vibration effect of ultrasonic waves, the incidence of adverse events resulting in dissection is reduced. In addition, when the cutting element penetrates the diseased tissue, the drug coating applied on the balloon and the cutting element will be instantly transported to the vascular endothelial tissue in the broken layer of the diseased tissue with the help of ultrasonic energy, thereby avoiding It eliminates the second interventional process of the drug balloon catheter, effectively reduces the cost, shortens the processing time, is safe and effective, and is more conducive to improving the treatment effect. In addition, the ultrasonic vibration energy is adjusted by the ultrasonic control device, so that the drug balloon catheter of the present invention has the ability to adapt to the treatment of blood vessels with complex lesions (containing calcification, fibrosis, and lipid pools).

Preferably, the cutting element extends along the central axis of the balloon. In this way, the cutting element can be easily installed on the surface of the balloon and can be scored along the extending direction of the blood vessel, making the structural arrangement of the drug balloon catheter more reasonable.

Preferably, a plurality of the cutting elements are distributed circumferentially around the central axis of the balloon. In this way, the cutting elements can be distributed on the surrounding surface of the balloon, so that the surrounding inner wall of the blood vessel can be treated at the same time and the processing time can be shortened.

Preferably, the cutting element includes a plurality of sawtooth blades and a connecting section connected between two adjacent sawtooth blades. By arranging a connecting section between two adjacent sawtooth blades, the flexibility of the drug balloon catheter area of the present invention ^can be improved, which is beneficial to passing through curved lesions.

Preferably, the proximal end of the catheter is provided with a needle seat, and the needle seat has at least three interfaces that communicate with the inside of the catheter to allow filling medium to pass and to accommodate wires.

Preferably, the surface of the balloon is provided with a groove, and the groove is filled with liposomes containing the drug. When the balloon is expanded, the opening of the groove becomes larger, so that the groove The liposomes inside are exposed and released outward.

Preferably, the drug balloon catheter further includes a sleeve, and the sleeve is removably placed outside the balloon. By providing a cannula, damage to normal blood vessels by the cutting element during balloon intervention can be prevented; and after the balloon reaches the target area, the cannula can be removed to expose the balloon and the cutting element. Therefore, The present invention can be easily inserted into blood vessels and improve the safety of use.

Description of drawings

Figure 1 is a structural diagram of the drug balloon catheter of the present invention.

Figure 2 is a cross-sectional view of the balloon of the drug balloon catheter of the present invention along the A-A direction.

Figure 3 is a cross-sectional view of the catheter of the drug balloon catheter of the present invention along the B-B direction.

Figure 4 is a structural diagram of the cutting element of the drug balloon catheter of the present invention.

Figure 5 is a diagram of a state in which the drug balloon catheter of the present invention is located in a blood vessel and is treating diseased tissue.

Detailed ways

In order to describe in detail the technical content, structural features, and achieved effects of the present invention, the following is a detailed description in combination with the embodiments and the accompanying drawings.

As shown in Figures 1 to 3, the drug balloon catheter 100 of the present invention includes a catheter 1, a balloon 2, a cutting element 3, a pressurizing device 4, a first electrode 5, a voltage control device 6, an ultrasonic generator 7 and an ultrasound Control device 8, the balloon 2 is arranged at the distal end of the catheter 1, the catheter 1 is provided with an inner tube 21, the inner tube 21 penetrates the entire catheter 1 and the interior of the balloon 2, and the inner tube 21 is used for For the guide wire to pass through, the front end of the balloon 2 is also provided with a tip 11. The channel 9 between the catheter 1 and the inner tube 21 is connected to the inflation device 4 for expanding or expanding the balloon 2. shrink. The cutting element 3 is arranged on the surface of the balloon 2 . The surface of the balloon 2 and the surface of the cutting element 3 are provided with drug coating. The first electrode 5 is disposed outside the distal end of the catheter 1 or outside the inner tube 21 and is located inside the balloon 2. The first electrode 5 is in non-contact with the inner wall of the balloon 2. relation. The voltage control device 6 is located at the proximal end of the catheter 1; the first electrode 5 is electrically connected to the first conductive end of the voltage control device 6 through the first wire 101, and the cutting element 3 serves as the second electrode And is electrically connected to the second conductive end of the voltage control device 6 through the second conductor 102. The first conductive end and the second conductive end have opposite polarities. More specifically, the first conductive end is the positive electrode. , the second conductive terminal is the negative electrode. The first wire 101 is welded to the side surface of the first electrode 5 , and the second wire 102 is welded to the side surface of the cutting element 3 . The first wire 101 and the second wire 102 are arranged in the catheter 1 . The voltage control device 6 includes a high-voltage pulse power supply, which is electrically connected to the cutting element 3 and the first electrode 5. When the high-voltage pulse power supply applies high-voltage pulses to the positive electrode and the negative electrode, Radio frequency energy can be generated between the cutting element 3 and the first electrode 5 . Providing radiofrequency energy in the form of modulated pulses from a radiofrequency energy source to the diseased tissue 201 from at least one of the cutting element 3 and the first electrode 5 can facilitate drug delivery to the vicinity of the diseased tissue 201 . In this embodiment, the pulse width of the modulated pulse is between about 0.08 microseconds and about 600 microseconds; the radio frequency energy voltage is between 400V and 4000V. By electrically connecting the first electrode 5 and the cutting element 3 to the voltage control device 6, the voltage control device 6 is used to adjust the voltage to a certain value, so that the first electrode 5 can move toward the The cutting element 3 emits radio frequency energy, which can promote the release of drugs, and the radio frequency energy transmitted to the lesion of the blood vessel 200 can cause the blood vessel 200 to relax and change the permeability of the cells. In addition, by modulating the radiofrequency signal, the drug can be delivered deeper into the inner wall of the blood vessel 200 , thereby allowing the drug to remain within the inner wall of the blood vessel 200 for a longer time and improving the durability of the drug within the blood vessel 200 , thus enhancing drug delivery and improve tissue drug absorption.

Please refer to Figures 1 to 3 again. The ultrasonic generator 7 is disposed around the outside of the inner tube 21 of the balloon 2 and inside the balloon 2. It can also be disposed outside the distal end of the catheter 1. , the ultrasonic control device 8 is located at the proximal end of the catheter 1; the ultrasonic generator 7 is electrically connected to the ultrasonic control device 8 through a third wire 103; the third wire 103 is provided in the catheter 1 . Ultrasonic energy is generated by the ultrasonic generator 7. After the ultrasonic energy is transmitted to the cutting element 3, the cutting element 3 has stronger cutting ability and improves the cutting ability of the cutting element 3 on the diseased components; at the same time, the ultrasonic wave is transmitted to the blood vessels through the cutting element 3 The inner wall of the blood vessel 200 impacts the diseased tissue 201, and the thrombus on the inner wall of the blood vessel 200 turns into small pieces and falls into the blood vessel 200 due to the cavitation effect of the ultrasonic waves. This can effectively treat the moderately and severely calcified diseased tissue 201. In addition, due to the improvement of the scoring ability of the cutting element 3, combined with the vibration effect of ultrasonic waves, the incidence of adverse events resulting in interlayers is reduced. In addition, when the cutting element 3 penetrates the diseased tissue 201, the drug coating applied on the balloon 2 and/or the cutting element 3 will be instantly transported to the fracture layer of the diseased tissue 201 with the help of ultrasonic energy. within the endothelial tissue of the blood vessel 200, thereby avoiding the second intervention process of the drug balloon catheter 100, effectively reducing the cost, shortening the processing time, being safe and effective, and more conducive to improving the treatment effect. In addition, the ultrasonic vibration energy is adjusted by the ultrasonic control device 8 so that the drug balloon catheter 100 of the present invention has the ability to adapt to the treatment of blood vessels 200 with complex lesions (including calcification, fibrosis, and lipid pools).

As shown in FIG. 4 , specifically, the cutting element 3 extends along the central axis direction of the balloon 2 . In this way, the cutting element 3 can be easily installed on the surface of the balloon 2 and can be scored along the extension direction of the blood vessel 200, making the structural arrangement of the drug balloon catheter 100 more reasonable. The cutting elements 3 are circumferentially distributed around the central axis of the balloon 2 . In this way, the cutting elements 3 can be distributed on the surrounding surface of the balloon 2, so that the surroundings of the inner wall of the blood vessel 200 can be processed simultaneously, and the processing time can be shortened. The cutting element 3 includes a plurality of sawtooth blades 31 and a connecting section 32 connected between two adjacent sawtooth blades 31 . The saw blades of the saw blade 31 are away from the central axis of the catheter 1 , and the cross section of the saw blade 31 is triangular. The length of the connecting section 32 is 1mm-3mm. By arranging the connecting section 32 between two adjacent sawtooth blades 31, the flexibility of the drug balloon catheter 100 area of the present invention can be improved, so that the passability of the drug balloon catheter 100 can be effectively improved, and the drug balloon catheter 100 can effectively The ability of the drug balloon catheter 100 provided in this embodiment to pass through tortuous blood vessels is improved.

In a preferred embodiment, the material of the saw blade 31 in this embodiment is an alloy. Of course, in other embodiments, the material of the saw blade 31 can also be pure metal, plastic, ceramic and other materials with higher hardness. .

In a preferred embodiment, the height of the sawtooth blade 31 in this embodiment ranges from 0.05 to 5mm, and the length of the sawtooth blade 31 ranges from 1 to 50mm.

In a preferred embodiment, the number of sawtooth blades 31 in this embodiment is determined according to the length of the balloon 2 .

In a preferred embodiment, the length of the connecting section 32 in this embodiment ranges from 0.5 to 10 mm, and the material of the connecting section 32 is silica gel. Of course, in other embodiments, the connecting section 32 in this embodiment The material can also be thermoplastic polyurethane elastomer, polyether block polyamide, nylon and other polymer materials with good flexibility.

As shown in Figure 1, the drug balloon catheter 100 also includes a developing member 104. The developing member 104 is disposed at the distal end of the catheter 1 and located inside the balloon 2. The developing member 104 has an outer surface. The edge is aligned with the edge of the balloon 2 . The development 104 is visible under X-rays and can mark the position of the balloon 2 during surgery.

Please refer to Figure 1 again. The proximal end of the catheter 1 is provided with a needle seat 105. The needle seat 105 has at least three interfaces connected to the inside of the catheter 1, of which the first interface 105a is connected to the inside of the inner tube 21. The cavities are connected to allow guidewires to pass through. The second interface 105b is connected to the channel 9 for filling with medium. The other interface 105c allows the first wire 101, the second wire 102 and the third wire 103 to pass through.

The surface of the balloon 2 is provided with grooves (not shown in the figure), and the grooves are filled with drug-containing liposomes, and the liposomes contain drug nanoparticles. When the balloon 2 expands, the opening of the groove becomes larger, causing the liposomes in the groove to be exposed and released; when the balloon 2 contracts, the liposomes Being wrapped by the balloon 2 prevents the drug from being released.

Specifically, the liposomes have targeting properties, sustained release properties, and cell affinity, and the liposomes have a certain sensitivity to ultrasound. Under the action of ultrasound, the liposome-encapsulated drug nanoparticles can Rapidly released, liposomes can greatly improve the efficiency of drug transport across membranes, effectively organize the absorption rate of active drugs, and improve the effectiveness of surgery. The size of liposomes can be between 0.1um-10um, such as 0.5um, 0.7um, 1um, 1.5um, 2um, 2.5um, 3um, 3.5um, 4.5um and 5um, etc. Smaller particles are beneficial to organization. Absorption can also further prevent the accumulation of liposomes from clogging blood vessels.

This application uses liposomes to improve the stability of the drug coating to reduce the impact of blood erosion on the drug coating during the delivery process, effectively prevent the drug coating from falling off, and reduce waste.

The liposome is selected from dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylethanolamine (DPPE), distearoylphosphatidylcholine (DSPC) ), dilauroyl lecithin (DLPC) or a combination of at least two, preferably distearoylphosphatidylcholine (DSPC) and/or dipalmitoylphosphatidylcholine (DPPC).

The drug balloon catheter 100 also includes a sleeve (not shown in the figure), which is removably placed outside the balloon 2 . By providing a cannula, damage to the normal blood vessels 200 by the cutting element 3 during the intervention of the balloon 2 can be prevented; and after the balloon 2 reaches the target area, the cannula can be removed to expose the balloon 2 and The cutting element 3 therefore allows the present invention to be easily inserted into the blood vessel 200 and improves the safety of use.

Based on the above and in conjunction with Figure 5, the operation process of the drug balloon catheter 100 of the present invention is described in detail below, which includes the following steps:

Step S1: Establish a channel; specifically, after the percutaneous puncture is successful, push the guide wire to the target area of the blood vessel 200, and send the distal end of the drug balloon catheter 100, that is, the inner tube 21, to the target area along the guide wire, and pass through the channel 9 The balloon 2 is inflated to expand, and the cutting element 3 is in close contact with the inner wall of the blood vessel 200 .

Step S2: Cut the diseased tissue 201; specifically, repeatedly shrink and expand the balloon 2 so that the cutting element 3 cuts the calcification and forms a crack so that the medicine can enter the deep layer of the diseased tissue 201.

Step S3: Release the drug; specifically, keep the cutting element 3 embedded in the diseased tissue 201, start the ultrasonic control device 8, the ultrasonic generator 7 works, ultrasonic cracks and shatters the calcified material, and at the same time promotes the release of the drug to the blood vessel 200; at the same time or At the same time or later, the voltage control device 6 is started to generate radio frequency energy between the cutting element 3 and the first electrode 5 to promote drug delivery to the blood vessel 200; this is maintained for a certain period of time until the drug is fully released to the inner wall of the blood vessel 200.

Step S4: Exit; specifically, close the ultrasonic control device 8 and the voltage control device 6, release the pressure through the channel 9, shrink the balloon 2, and return the drug balloon catheter 100 to the outside of the body along the guide wire, and apply local pressure to stop bleeding or suture. The device is sutured to stop the bleeding and the interventional treatment process is completed.

The above-mentioned steps S2 and S3 can also be performed simultaneously. On the premise of keeping the balloon 2 in contact with the blood vessel 200 , multiple times of inflating and releasing pressure cause the cutting element 3 to move radially, so that the cutting element 3 further enters the diseased tissue 201 of depth.

Compared with the prior art, the present invention sets a balloon 2 at the distal end of the catheter 1 so that the balloon 2 communicates with the inflation device 4 through the channel 9. Therefore, the inflation device 4 can be used to control the inflation device 4. The balloon 2 contracts and expands, so that the balloon 2 can expand the blood vessel 200; and can release the drug coated on the surface at the lesion. By arranging a cutting element 3 on the surface of the balloon 2, the contraction and expansion of the balloon 2 can drive the cutting element 3 to score or cut the diseased tissue 201, so that the medicine can penetrate deeper into the diseased tissue 201 more quickly. Deep in the diseased tissue 201; furthermore, by arranging the first electrode 5 and the ultrasonic generator 7, and by energizing the first electrode 5 and the cutting element 3, radio frequency energy is generated between the first electrode 5 and the cutting element 3, so that the The drug is delivered deeper into the inner wall of the blood vessel 200 , and at the same time, the ability of the cutting element 3 to score the diseased component is improved through the action of ultrasound, thereby effectively treating the calcified diseased tissue 201 . Therefore, the drug balloon catheter 100 of the present invention can not only increase the drug release rate of the balloon 2, but also increase the drug absorption rate of the tissue, thereby improving the therapeutic effect.

In addition, the drug delivery loss rate, absorption rate and residual amount of the drug balloon catheter 100 of the present invention can be determined through multiple embodiment tests and comparisons, so that the effect of the drug balloon catheter 100 of the present invention can be further determined. The following is a comparative explanation through examples.

The drug loss during the delivery process of the drug balloon catheter refers to the time when the expandable balloon of the drug balloon catheter is inserted into the guide catheter, and the expandable balloon is gradually pushed to the target blood vessel at the lesion site until the expandable balloon is filled. The amount of drug lost during the previous period. The ratio of the drug dose loss during the delivery process to the initial drug dose on the surface of the expandable balloon is the drug dose loss rate during the delivery process.

The drug loss test during the delivery process was conducted in an in vitro simulated blood vessel model. The specific method is: sleeve the drug balloon catheters prepared in Examples 1-6 and Comparative Example 1 respectively, and then put the drug balloons into The catheter is inserted into the in vitro simulated blood vessel model, transported along the simulated blood vessel path to the target blood vessel, and stays there. The timing starts when the drug balloon catheter is inserted into the in vitro simulated blood vessel model, and the drug balloon catheter is removed after 60 seconds. Use HPLC to analyze the residual drug amount on the surface of the expandable balloon, and calculate the drug loss rate during the delivery process as follows:

Drug loss rate during delivery = (initial drug amount on the surface of the expandable balloon - residual drug amount on the surface of the expandable balloon)/initial drug amount on the surface of the expandable balloon × 100%.

HPLC detection conditions are as follows: Japan's Shimadzu LC-20A high-performance liquid chromatograph is used. Chromatographic column: American Agilent ZOBAXSB-C18 column (4.6×250 mm, 5 μm). Column temperature: 30℃. Mobile phase: methanol: acetonitrile: water = 230:360:410. Flow rate: 1.0mL/min. UV detector. Detection wavelength: 227nm.

Examples 1-6 use the same drug balloon catheter 100 of the present invention (drug loading 1.3 μg/mm ² , 40 mg in total). Comparative Example 2 is Example 1 without the sleeve, and Comparative Example 1 is the drug balloon used. The difference between the balloon and the drug balloon catheter of Embodiment 1 is that there is no cutting element, ultrasonic element, or first electrode, and the others are the same.

1. Example 1

In vitro transfer rate test:

The drug balloon catheter provided in Example 1 was subjected to an in vitro simulation transfer rate test. In the in vitro simulation test model, the isolated pig coronary blood vessel was used as the target blood vessel for balloon expansion. The drug balloon catheter provided in Example 1 was separately Insert it into the in vitro simulated blood vessel model, transport it along the simulated blood vessel path to the target blood vessel and stay there. The timer starts when the drug-eluting balloon catheter is inserted into the in vitro simulated blood vessel model. After 60 seconds, the drug-eluting balloon catheter is expanded and the balloon fluid is filled to About 12 atm, the over-expansion rate (the ratio of balloon diameter to blood vessel diameter) is

1.10~1.20; The drug is delivered to the vascular tissue within 1 minute of liquid filling time, and then the filling liquid is withdrawn to deflate the balloon and taken out from the in vitro simulation test system to collect the target vascular tissue.

Through tissue extraction and HPLC (Shimadzu LC-20A high performance liquid chromatography, Japan, chromatographic column: AglilentZOBAXSB-C18 4.6×250mm, 5um, mobile phase: methanol: acetonitrile: water = 230:360:410, column temperature: 30°C , detection wavelength: 227nm (UV detector), flow rate: 1.0ml/min), detect the drug content in the vascular tissue, and evaluate the drug transfer rate of the drug balloon to the vascular tissue.

Drug residue rate test:

For the drug residual rate on the balloon surface, take out the used balloon catheter, cut and grind it, and adjust the volume to 2 mL. Then use a liquid chromatograph to measure the drug content in the solution, and calculate the drug residual rate.

2. Example 2

In vitro transfer rate test:

The drug balloon catheter provided in Example 1 was subjected to an in vitro simulation transfer rate test. In the in vitro simulation test model, the isolated pig coronary blood vessels were used as the target blood vessels for balloon expansion, and the drug balloon catheter provided in Example 2 was separately Insert it into the in vitro simulated blood vessel model, transport it along the simulated blood vessel path to the target blood vessel and stay there. The timer starts when the drug-eluting balloon catheter is inserted into the in vitro simulated blood vessel model. After 60 seconds, the drug-eluting balloon catheter is expanded and the balloon fluid is filled to About 12 atm, the over-expansion rate (the ratio of balloon diameter to blood vessel diameter) is 1.10 to 1.20; the drug is transported to the vascular tissue within the liquid filling time of 1 minute (repeated inflation for 10 seconds, 6 times), and then withdrawn The balloon is deflated by filling with liquid and taken out from the in vitro simulation test system to collect target vascular tissue.

Through tissue extraction and HPLC (Shimadzu LC-20A high performance liquid chromatography, Japan, chromatographic column: AglilentZOBAXSB-C18 4.6×250mm, 5um, mobile phase: methanol: acetonitrile: water = 230:360:410, column temperature: 30°C , detection wavelength: 227nm (UV detector), flow rate: 1.0ml/min), detect the drug content in the vascular tissue, and evaluate the drug transfer rate of the drug balloon to the vascular tissue.

Drug residue rate test:

For the drug residual rate on the balloon surface, take out the used balloon catheter, cut and grind it, and adjust the volume to 2 mL. Then use a liquid chromatograph to measure the drug content in the solution, and calculate the drug residual rate.

3. Example 3

In vitro transfer rate test:

The drug balloon catheter provided in Example 1 was subjected to an in vitro simulation transfer rate test. In the in vitro simulation test model, the isolated pig coronary blood vessel was used as the target blood vessel for balloon expansion, and the drug balloon catheter provided in Example 3 was used. Insert it into the in vitro simulated blood vessel model, transport it along the simulated blood vessel path to the target blood vessel and stay there. The timer starts when the drug-eluting balloon catheter is inserted into the in vitro simulated blood vessel model. After 60 seconds, the drug-eluting balloon catheter is expanded and the balloon fluid is filled to About 12 atm, the over-expansion rate (the ratio of balloon diameter to blood vessel diameter) is 1.10 to 1.20; the liquid filling of the drug in 1 minute (repeated filling for 10 seconds, 6 times, during which the ultrasound is turned on, the frequency is 5MHz, the ultrasound action time is 60s) It is delivered to the vascular tissue within a certain period of time, and then the filled liquid is withdrawn to deflate the balloon, and is taken out from the in vitro simulation test system to collect the target vascular tissue.

Through tissue extraction and HPLC (Shimadzu LC-20A high performance liquid chromatography, Japan, chromatographic column: AglilentZOBAXSB-C18 4.6×250mm, 5um, mobile phase: methanol: acetonitrile: water = 230:360:410, column temperature: 30°C , detection wavelength: 227nm (UV detector), flow rate: 1.0ml/min), detect the drug content in the vascular tissue, and evaluate the drug transfer rate of the drug balloon to the vascular tissue.

Drug residue rate test:

For the drug residual rate on the balloon surface, take out the used balloon catheter, cut and grind it, and adjust the volume to 2 mL. Then use a liquid chromatograph to measure the drug content in the solution, and calculate the drug residual rate.

4. Example 4

In vitro transfer rate test:

The drug balloon catheter provided in Example 1 was subjected to an in vitro simulation transfer rate test. In the in vitro simulation test model, the isolated pig coronary blood vessel was used as the target blood vessel for balloon expansion, and the drug balloon catheter provided in Example 6 was used. Insert it into the in vitro simulated blood vessel model, transport it along the simulated blood vessel path to the target blood vessel and stay there. The timer starts when the drug-eluting balloon catheter is inserted into the in vitro simulated blood vessel model. After 60 seconds, the drug-eluting balloon catheter is expanded and the balloon fluid is filled to About 12 atm, the over-expansion rate (the ratio of balloon diameter to blood vessel diameter) is 1.10 to 1.20; the drug is inflated for 1 minute (repeatedly inflated for 10 seconds, 3 times, keeping the balloon in contact with the blood vessel, and then turning on ultrasound, frequency 5MHz, ultrasonic action The balloon is delivered to the vascular tissue during the liquid filling period of 30 seconds, and then the filled liquid is withdrawn to deflate the balloon, and is taken out from the in vitro simulation test system to collect the target vascular tissue.

Through tissue extraction and HPLC (Shimadzu LC-20A high performance liquid chromatography, Japan, chromatographic column: AglilentZOBAXSB-C18 4.6×250mm, 5um, mobile phase: methanol: acetonitrile: water = 230:360:410, column temperature: 30°C , detection wavelength: 227nm (UV detector), flow rate: 1.0ml/min), detect the drug content in the vascular tissue, and evaluate the drug transfer rate of the drug balloon to the vascular tissue.

Drug residue rate test:

For the drug residual rate on the balloon surface, take out the used balloon catheter, cut and grind it, and adjust the volume to 2 mL. Then use a liquid chromatograph to measure the drug content in the solution, and calculate the drug residual rate.

5.Example 5

In vitro transfer rate test:

The drug balloon catheter provided in Example 1 was subjected to an in vitro simulation transfer rate test. In the in vitro simulation test model, the isolated pig coronary blood vessels were used as the target blood vessels for balloon expansion, and the drug balloon catheter provided in Example 5 was separately Insert it into the in vitro simulated blood vessel model, transport it along the simulated blood vessel path to the target blood vessel and stay there. The timer starts when the drug-eluting balloon catheter is inserted into the in vitro simulated blood vessel model. After 60 seconds, the drug-eluting balloon catheter is expanded and the balloon fluid is filled to About 12 atm, the over-expansion rate (the ratio of balloon diameter to blood vessel diameter) is 1.10 to 1.20; the drug is inflated for 1 minute (repeatedly inflated for 5 seconds, 3 times, keeping the balloon in contact with the blood vessel, and then turning on the voltage control system. The voltage pulse width 100 microseconds, voltage 1000V, voltage action time 15s, then turn on the ultrasound (ultrasonic frequency 5MHz, ultrasound action time 30s) to be transported to the vascular tissue within the liquid filling time, and then withdraw the filled liquid to deflate the balloon and remove it from the Take it out from the in vitro simulation test system and collect the target vascular tissue.

Through tissue extraction and HPLC (Shimadzu LC-20A high performance liquid chromatography, Japan, chromatographic column: AglilentZOBAXSB-C18 4.6×250mm, 5um, mobile phase: methanol: acetonitrile: water = 230:360:410, column temperature: 30°C , detection wavelength: 227nm (UV detector), flow rate: 1.0ml/min), detect the drug content in the vascular tissue, and evaluate the drug transfer rate of the drug balloon to the vascular tissue.

Drug residue rate test:

For the drug residual rate on the balloon surface, take out the used balloon catheter, cut and grind it, and adjust the volume to 2 mL. Then use a liquid chromatograph to measure the drug content in the solution, and calculate the drug residual rate.

6.Example 6

In vitro transfer rate test:

The drug balloon catheter provided in Example 1 was subjected to an in vitro simulation transfer rate test. In the in vitro simulation test model, the isolated pig coronary blood vessel was used as the target blood vessel for balloon expansion. The drug balloon catheter provided in Example 1 was separately Insert it into the in vitro simulated blood vessel model, transport it along the simulated blood vessel path to the target blood vessel and stay there. The timer starts when the drug-eluting balloon catheter is inserted into the in vitro simulated blood vessel model. After 60 seconds, the drug-eluting balloon catheter is expanded and the balloon fluid is filled to About 12 atm, the over-expansion rate (the ratio of balloon diameter to blood vessel diameter) is 1.10 to 1.20; the drug is inflated for 1 minute (repeatedly inflated for 5 seconds, 3 times, keeping the balloon in contact with the blood vessel, and then turning on the ultrasonic and voltage control system, the ultrasonic The frequency is 5MHz, the voltage pulse width is 100 microseconds, the voltage is 1000V, and the ultrasound and voltage action time is 45s). It is delivered to the vascular tissue during the liquid filling period, and then the filled liquid is withdrawn to deflate the balloon and remove it from the in vitro simulation test system. Take it out and collect the target blood vessel tissue.

Through tissue extraction and HPLC (Shimadzu LC-20A high performance liquid chromatography, Japan, chromatographic column: AglilentZOBAXSB-C18 4.6×250mm, 5um, mobile phase: methanol: acetonitrile: water = 230:360:410, column temperature: 30°C , detection wavelength: 227nm (UV detector), flow rate: 1.0ml/min), detect the drug content in the vascular tissue, and evaluate the drug transfer rate of the drug balloon to the vascular tissue.

Drug residue rate test:

For the drug residual rate on the balloon surface, take out the used balloon catheter, cut and grind it, and adjust the volume to 2 mL. Then use a liquid chromatograph to measure the drug content in the solution, and calculate the drug residual rate.

7. Comparative Example 1

The difference between the drug balloon used and the drug balloon catheter in Embodiment 1 is that there is no cutting element, ultrasonic element, or first electrode, and the others are the same.

The drug balloon catheter provided was subjected to an in vitro simulation transfer rate test. In the in vitro simulation test model, the isolated pig coronary vessels were used as the target blood vessels for balloon expansion, and the drug balloon catheters provided in Example 1 were inserted into the in vitro simulation test model. In the vascular model, the drug is transported along the simulated vascular path to the target blood vessel and stays there. The drug-eluting balloon catheter is inserted into the in vitro simulated vascular model and starts timing. After 60 seconds, the drug-eluting balloon catheter is expanded and the balloon fluid is filled to about 12 atm. The expansion rate (the ratio of balloon diameter to blood vessel diameter) is 1.10 to 1.20; the drug is delivered to the vascular tissue within 1 minute of liquid filling time, and then the filling liquid is withdrawn to deflate the balloon and removed from the in vitro simulation test system Take it out and collect the target blood vessel tissue.

Through tissue extraction and HPLC (Shimadzu LC-20A high performance liquid chromatography, Japan, chromatographic column: AglilentZOBAXSB-C18 4.6×250mm, 5um, mobile phase: methanol: acetonitrile: water = 230:360:410, column temperature: 30°C , detection wavelength: 227nm (UV detector), flow rate: 1.0ml/min), detect the drug content in the vascular tissue, and evaluate the drug transfer rate of the drug balloon to the vascular tissue.

Drug residue rate test:

For the drug residual rate on the balloon surface, take out the used balloon catheter, cut and grind it, and adjust the volume to 2 mL. Then use a liquid chromatograph to measure the drug content in the solution, and calculate the drug residual rate.

8. Comparative Example 2

In vitro transfer rate test:

The drug balloon catheter provided in Comparative Example 2 was subjected to an in vitro simulation transfer rate test. In the in vitro simulation test model, isolated pig coronary vessels were used as the target blood vessels for balloon expansion. The drug balloon catheter provided in Comparative Example 2 ( Remove the cannula) and insert them into the in vitro simulated blood vessel model respectively, transport them along the simulated blood vessel path to the target blood vessel and stay there, start timing when the drug-eluting balloon catheter is inserted into the in vitro simulated blood vessel model, and expand the drug balloon catheter after 60 seconds. The balloon is filled with liquid to about 12 atm, and the over-expansion rate (the ratio of balloon diameter to blood vessel diameter) is 1.10 to 1.20; the drug is delivered to the vascular tissue within 1 minute of liquid filling time, and then the filled liquid is withdrawn to deflate the balloon. Deflate and remove from the in vitro simulation test system to collect target vascular tissue.

Through tissue extraction and HPLC (Shimadzu LC-20A high performance liquid chromatography, Japan, chromatographic column: AglilentZOBAXSB-C18 4.6×250mm, 5um, mobile phase: methanol: acetonitrile: water = 230:360:410, column temperature: 30°C , detection wavelength: 227nm (UV detector), flow rate: 1.0ml/min), detect the drug content in the vascular tissue, and evaluate the drug transfer rate of the drug balloon to the vascular tissue.

Drug residue rate test:

For the drug residual rate on the balloon surface, take out the used balloon catheter, cut and grind it, and adjust the volume to 2 mL. Then use a liquid chromatograph to measure the drug content in the solution, and calculate the drug residual rate.

The experimental results are shown in the table below:

The following table shows the control experiment results of Examples 1-6 and Comparative Examples 1-2 of the drug balloon catheter 100:

As can be seen from Table 1, using the drug balloon catheter 100 provided by the embodiment of the present invention, by adding the cutting element 3, the first electrode 5 and the ultrasonic generator 7, the radio frequency between the first electrode 5 and the cutting element 3 is used. The energy and ultrasonic waves generated by the ultrasonic generator can significantly increase the tissue drug concentration and tissue drug absorption rate, and significantly reduce the drug residual rate on the balloon 2.

Comparing Example 1 with Comparative Example 1, the cutting function of the cutting element 3 works, improves the absorption rate of the drug, and reduces the residual rate of the drug;

Comparing Example 2 with Example 1, the repeated charging function works to increase the absorption rate of the drug and reduce the residual rate of the drug;

Comparing Example 1 with Comparative Example 2, the cannula works and reduces the drug delivery loss rate;

Comparing Example 3 with Example 2, the function of ultrasonic waves works to increase the absorption rate of the drug and reduce the residual rate of the drug;

Comparing Example 4 with Example 2, the function of ultrasonic waves works to increase the absorption rate of the drug and reduce the residual rate of the drug;

Comparing Example 5 with Example 4, the radio frequency energy between the first electrode 5 and the cutting element 3 works to increase the absorption rate of the drug and reduce the residual rate of the drug;

Comparing Example 6 with Example 4, the radio frequency energy between the first electrode 5 and the cutting element 3 acts to increase the absorption rate of the drug and reduce the residual rate of the drug;

Comparing Example 6 with Example 5, radiofrequency energy is first used to increase tissue permeability, and then ultrasound is used to promote the release of the drug, which has a better effect.

The structures and principles of the voltage control device 6 and the ultrasonic control device 8 involved in the drug balloon catheter 100 of the present invention are well known to those of ordinary skill in the art, and will not be described in detail here.

What is disclosed above is only the preferred embodiment of the present invention. Of course, it cannot be used to limit the scope of rights of the present invention. Therefore, equivalent changes made according to the patent scope of the present invention still fall within the scope of the present invention.

Claims (10)

1. A drug balloon catheter, characterized by: the device comprises a catheter, a balloon, a cutting element, a pressurizing device, a first electrode and a voltage control device, wherein the balloon is arranged at the distal end of the catheter, the balloon is communicated with the pressurizing device through a channel, and the channel is arranged in the catheter; the cutting element is arranged on the surface of the balloon; the surface of the balloon and/or the surface of the cutting element is provided with a drug coating; the first electrode is arranged outside the distal end of the catheter and inside the balloon, and the voltage control device is positioned at the proximal end of the catheter; the first electrode is electrically connected with a first conductive end of the voltage control device through a first wire, and the cutting element is used as a second electrode and is electrically connected with a second conductive end of the voltage control device through a second wire; the first and second conductive ends being of opposite polarity, the voltage control means being capable of generating radio frequency energy between the cutting element and the first electrode when a high voltage pulse is applied to the cutting element and the first electrode; the first lead and the second lead are arranged in the catheter.

2. The drug balloon catheter of claim 1, wherein: the high voltage pulse has a pulse width of between about 0.08 microseconds and about 600 microseconds.

3. The drug balloon catheter of claim 1, wherein: the radio frequency energy voltage is between 400V and 4000V.

4. The drug balloon catheter of claim 1, wherein: the drug balloon catheter further comprises an ultrasonic generator and an ultrasonic control device, wherein the ultrasonic generator is arranged in the balloon; the ultrasonic generator is electrically connected with the ultrasonic control device through a third wire; the third wire is disposed within the catheter.

5. The drug balloon catheter of claim 1, wherein: the cutting element extends in a direction of a central axis of the balloon.

6. The drug balloon catheter of claim 1, wherein: a plurality of the cutting elements are circumferentially distributed about a central axis of the balloon.

7. The drug balloon catheter of claim 1, wherein: the cutting element comprises a plurality of saw tooth sheets and a connecting section connected between two adjacent saw tooth sheets.

8. The drug balloon catheter of claim 1, wherein: the proximal end of the catheter is provided with a needle seat, and the needle seat is provided with at least three interfaces communicated with the interior of the catheter for the pipeline to pass through.

9. The drug balloon catheter of claim 1, wherein: the surface of the sacculus is provided with a groove, the groove is filled with liposome containing medicine, and the opening of the groove is enlarged, so that the liposome in the groove is exposed and released outwards.

10. The drug balloon catheter of any one of claims 1-9, wherein: the drug balloon catheter also comprises a sleeve which is detachably sleeved outside the balloon.