Coronary drug balloon with fast drug effect penetration

Abstract

The invention discloses a coronary drug balloon with fast drug effect penetration, and relates to the technical field of interventional instruments, and the coronary drug balloon is characterized by comprising a balloon body, an inner tube is arranged in the balloon body in a penetrating manner, and a developing ring located on the inner side of the balloon body is arranged on the periphery of the inner tube in an attached manner; the two ends of the balloon body are both conical, the main body portion of the balloon body is cylindrical, the periphery of the main body portion of the balloon body is coated with a medicine coating, the front end of the inner tube extends to the outer side of the balloon body, a tip is constructed at the front end of the inner tube, a protective sleeve is connected to the tip in an inserted mode, and the protective sleeve is sleeved with the inner tube. The beneficial effects are that the hydrophilic coating is arranged behind the blood flowing direction of the active medicine, the absorption effect of the active medicine can be improved in an auxiliary manner, and the problem that a large amount of medicine is washed by blood flowing at a high speed before being absorbed by vascular tissue and is lost is solved; and the treatment effect of the medicine balloon is effectively improved.

Description

Technical Field

[0001] The present invention relates to the technical field of interventional instruments, and more particularly to a coronary drug balloon with fast drug penetration. Background Art

[0002] With the increase in stent implantation, the number of patients with in-stent restenosis also increases. In addition, with the increase in angiography, the number of patients with small vessel lesions who cannot undergo stent implantation also increases. Some patients cannot use dual antiplatelet drugs for a long time due to problems such as gastrointestinal ulcers. In the face of these situations, drug-eluting balloons provide a new treatment method for patients who cannot undergo stent implantation.

[0003] The drug-coated balloon is an interventional device. Its principle is to load active drugs on the surface of an ordinary balloon, deliver them to the target lesion site of the blood vessel, and then inflate the balloon to allow the drug to fully contact the blood vessel wall, thereby eliminating the long-term stenosis of the target lesion site.

[0004] Except for capillaries and lymphatic capillaries, the vascular wall is generally divided into the intima, media and adventitia from the lumen to the outside. The intima is the innermost layer of the vascular wall, composed of the endothelium and the subendothelial layer. The endothelial cells and the substrate constitute a permeable dense barrier, through which liquids, gases and macromolecules can selectively pass into the media. The thickness and composition of the media vary depending on the type of blood vessel. The large arteries are mainly composed of elastic membranes with a small amount of smooth muscle in between; the middle arteries are mainly composed of smooth muscle. Therefore, in drug-coated balloon intervention, the drug coating on the balloon surface is eluted from the balloon surface and released into the blood vessels at the lesion site after reaching the target lesion site, but it cannot actually fully exert its efficacy. Among them, only drugs that are absorbed by the vascular intima and enter the smooth muscle cell layer of the vascular media can exert their therapeutic effects, inhibit the malignant proliferation of smooth muscle cells and reduce the restenosis rate.

[0005] Since restenosis is a chronic process, the more drugs are absorbed by the intima and enter the vascular media, the longer the drugs stay in the target lesion site, and the better the effect of inhibiting restenosis. However, during the short period of several minutes when the balloon is in contact with the target lesion, when the drug coating is released from the balloon surface to the inner wall of the blood vessel, the drug is absorbed by the vascular endothelium at a very slow rate, and a large amount of the drug is washed away by the high-speed blood flow before being absorbed. It is impossible to ensure that a sufficient amount of drugs can pass through the intima and enter the vascular media to inhibit the malignant proliferation of smooth muscle cells, and it is even more impossible to ensure long-term inhibition of restenosis.

[0006] Therefore, in order to solve the above technical problems, the present application proposes a coronary drug-eluting balloon with fast drug penetration. Summary of the invention

[0007] In view of the shortcomings of the prior art, the object of the present invention is to provide a coronary drug-eluting balloon with fast drug penetration.

[0008] To achieve the above object, the present invention provides the following technical solution: a coronary drug-eluting balloon with fast drug penetration, comprising

[0009] A balloon body, wherein an inner tube is inserted into the balloon body, and a developing ring is provided on the outer circumference of the inner tube and is located inside the balloon body. The developing ring is a disposable medical material and is used as a marking ring for X-ray developing marking of a remote working area in interventional treatment;

[0010] Both ends of the balloon body are constructed in a conical shape, and the main part of the balloon body is cylindrical. The outer periphery of the main part of the balloon body is coated with a drug coating. When gas is transported to the inner tube through a pipeline, air enters the balloon body, causing the balloon body to be in an expanded state. At this time, the drug coating is tightly attached to the inner periphery of the blood vessel under the action of the expanded balloon body.

[0011] Preferably, the front end of the inner tube extends to the outside of the balloon body, and the front end of the inner tube is configured with a tip, on which a protective sleeve is inserted, the protective sleeve is used to blunt the tip to prevent the tip from puncturing the blood vessel when the tip advances in the blood vessel, and to provide lubrication protection between the tip and the blood vessel, and the interior of the protective sleeve is provided with a protective wire extending to the inside of the inner tube, the protective wire has a certain toughness, to prevent the protective sleeve from bending at a large angle when the front side of the tip advances and causing folding of the front end of the inner tube.

[0012] Preferably, the end of the inner tube away from the protective sleeve is connected to a distal outer tube, and the outer periphery of the distal outer tube is coated with a hydrophilic coating. The hydrophilic coating is located on the rear side of the forward direction of the balloon body. When the drug coating dissolves, the part of the drug that is not absorbed by the vascular endothelium flows backward with the blood. At this time, the hydrophilic coating just dissolves, and the unabsorbed drug is mixed with the dissolved hydrophilic coating. With the help of the hydrophilic effect of the hydrophilic coating, the absorption of the unabsorbed drug can be assisted and optimized, thereby improving the therapeutic effect.

[0013] Preferably, a side port is provided on the distal outer tube, and the side port is connected to the proximal outer tube at one end away from the distal outer tube. The end of the proximal outer tube is connected to a transition joint, and the distal outer tube and the proximal outer tube are conveniently connected for use through the transition joint and the proximal outer tube.

[0014] Preferably, a hypotube is connected to the transition joint, and a symmetrically arranged visual mark is fitted on the outer circumference of the hypotube. The visual mark has the same function as a developing ring and is used as an X-ray developing mark of the remote working area.

[0015] Preferably, the end of the hypotube is connected to a catheter seat, and the hypotube can be easily pushed to move through the catheter seat.

[0016] Preferably, the drug coating is composed of a drug-carrying matrix and an active drug, and the drug-carrying matrix is ​​ioversol. After ioversol dissolves in the blood vessels, it causes a high iodine content in the blood vessels, causing X-ray attenuation, and enabling clear imaging of the blood vessels passing through until they are diluted.

[0017] Preferably, the active drug is disposed on the surface of the drug-carrying matrix and the content ranges from 2.5 to 3.0 μg / mm 2 , the active drug is an anti-intimal hyperplasia drug used to treat coronary artery stenosis.

[0018] Preferably, the active drug is paclitaxel, which can regulate the activity of anti-apoptotic mediators.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] 1. In the present invention, through the balloon body, the drug coating coated on the periphery of the balloon body and the hydrophilic coating coated on the periphery of the distal outer tube at the rear side of the forward direction of the balloon body, when the active drug in the drug coating adheres to the blood vessel wall and dissolves, a part of it is quickly absorbed by the vascular tissue, and the unabsorbed active drug flows backward with the blood and mixes with the dissolved hydrophilic coating. Under the action of the hydrophilic coating, the absorption effect of the active drug can be assisted and improved, which solves the problem that a large amount of drugs are washed away by the high-speed blood flow before being absorbed by the vascular tissue, and improves the therapeutic effect of the drug balloon;

[0021] 2. In the present invention, through the structural design of the balloon body, after the balloon body is expanded by inflating air into the balloon body through the pipeline, the blood vessels can be propped up from the inside, and a blood circulation channel of a certain area can be reserved to ensure normal blood circulation and avoid excessive reduction of the blood circulation area inside the blood vessels at the treatment site, resulting in a faster blood flow, which is beneficial to improving the absorption effect of the drug at the treatment site. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The drawings described herein are used to provide a further understanding of the present invention and constitute a part of this application. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0023] Figure 1 It is a structural schematic diagram of the present invention;

[0024] Figure 2 It is an end view of the balloon body in the present invention.

[0025] In the figure: 1. catheter seat; 2. hypotube; 3. visual marker; 4. transition joint; 5. proximal outer tube; 6. side port; 7. distal outer tube; 8. hydrophilic coating; 9. inner tube; 10. developing ring; 11. balloon body; 12. drug coating; 13. protective wire; 14. protective sleeve. DETAILED DESCRIPTION

[0026] like Figure 1-2 As shown, the present invention provides a coronary drug balloon with fast drug penetration, including a balloon body 11, an inner tube 9 is penetrated inside the balloon body 11, a developing ring 10 is fitted on the outer periphery of the inner tube 9 and is located on the inner side of the balloon body 11, both ends of the balloon body 11 are constructed in a conical shape, and the main part of the balloon body 11 is cylindrical, and the outer periphery of the main part of the balloon body 11 is coated with a drug coating 12, the drug coating 12 is composed of a drug-carrying matrix and an active drug, and the drug-carrying matrix is ​​ioversol, and a hydrophilic spacer is added to ioversol. The drug ball with a simple paclitaxel coating has a problem of low bioavailability, and on the basis of paclitaxel, adding some hydrophilic spacers to ioversol can improve the bioavailability of paclitaxel, increase the contact area between the drug and the blood vessel wall, and weaken the attraction between drug molecules, and the active drug is arranged on the surface of the drug-carrying matrix, and the content ranges from 2.5 to 3.0 μg / mm 2 The active drug selected is paclitaxel, which can regulate the activity of anti-apoptotic mediators, ensure the activity of vascular lining cells in the treatment area, and avoid shrinkage of vascular walls after cell inactivation.

[0027] The front end of the inner tube 9 extends to the outside of the balloon body 11. The front end of the inner tube 9 is structured with a tip, and a protective sleeve 14 is inserted on the tip. The protective sleeve 14 is made of latex material, has a smooth surface, and has a better guiding effect in the blood vessel. The inside of the protective sleeve 14 is provided with a protective wire 13 extending to the inside of the inner tank. The protective wire 13 can improve the toughness of the protective sleeve 14 and prevent the protective sleeve 14 from bending and deforming at will. The end of the inner tube 9 away from the protective sleeve 14 is connected to the distal outer tube 7, and the outer periphery of the distal outer tube 7 is coated with a hydrophilic coating. Layer 8, a side port 6 is provided on the distal outer tube 7, and the side port 6 is connected to the proximal outer tube 5 at one end away from the distal outer tube 7, the end of the proximal outer tube 5 is connected to a transition joint 4, a hypotube 2 is connected to the transition joint 4, the outer periphery of the hypotube 2 is fitted with symmetrically arranged visual marks 3, the end of the hypotube 2 is connected to a catheter seat 1, the distal outer tube 7, the side port 6, the proximal outer tube 5, the transition joint 4 and the hypotube 2 are all sealed and connected, and are used to introduce gas into the inner tube 9 to expand the balloon body 11 to an expanded state.

[0028] Drug clinical trials

[0029] A total of 223 subjects (110 in the experimental group and 113 in the control group) were screened and included in the full analysis set (FAS), 210 subjects (102 in the experimental group and 108 in the control group) were included in the per-protocol set (PPS), and 223 subjects (110 in the experimental group and 113 in the control group) were included in the safety analysis set (SS).

[0030] The baseline age, gender, ethnicity, history of drug or other allergies, smoking history, drinking history, electrocardiogram and echocardiogram examination, diagnosis of coronary heart disease, and medical history of the two groups were compared between the two groups. There was no statistically significant difference in the above indicators (P>0.05). At the same time, there was no statistically significant difference in the vital signs of the two groups, such as height, weight, BMI, heart rate, temperature, blood pressure, and respiration (P>0.05). The previous and preoperative medication and combined medication, the distribution of preoperative target lesion sites, the preoperative reference target vessel diameter, the preoperative target lesion degree, the preoperative diameter stenosis degree, the preoperative TIMI blood flow, the puncture route, the use of angiographic catheter models, the pre-dilation, the immediate postoperative diameter stenosis degree, the post-intervention TIMI blood flow, whether there was a dissection after the intervention, whether there was post-dilation after the intervention, the post-intervention rescue treatment, and the occurrence of complications during the interventional treatment were basically similar between the two groups, meeting the comparability requirements.

[0031] Table 1. Statistical analysis results of the main endpoint indicators:

[0032]

[0033] The primary endpoint of the study was the degree of target lesion diameter stenosis (%) 9 months after surgery.

[0034] As shown in Table 1, based on 223 subjects in the full analysis set (FAS), the covariance analysis model was used, and the corrected means of the diameter stenosis degree (%) of the two groups were 27.326% in the experimental group and 29.654% in the control group, the corrected mean difference was -2.328%, and the 95% confidence interval of the difference was -5.003% to 0.346%; based on 210 subjects in the per-protocol set (PPS), the covariance analysis model was used, and the corrected means of the diameter stenosis degree (%) of the two groups were 27.369% in the experimental group and 29.449% in the control group, the corrected mean difference was -2.081%, and the 95% confidence interval of the difference was -4.798% to 0.637%, and the upper limit of the confidence interval was lower than the non-inferiority margin (5%) of this study, so the non-inferiority was established, indicating that the experimental group was not inferior to the control group.

[0035] Table 2. Statistical analysis results of secondary endpoint indicators:

[0036]

[0037] Combined with what is shown in Table 2, it was concluded that among the secondary efficacy indicators, the results based on the full analysis set showed that there were no significant differences in the device success rate, surgical success rate, and clinical success rate between the two groups (p>0.05), and the incidence rates in the experimental group were slightly higher than those in the control group.

[0038] There were no significant differences in the minimum lumen diameter of the target lesion, late lumen loss of the target lesion, and restenosis rate of the target lesion 9 months after surgery between the two groups (p>0.05). During the entire postoperative follow-up period, the full analysis focused trial group had a device-related composite endpoint (DoCE), namely, 1 case of target lesion failure event, with an incidence of 0.9% (1 / 110), and the type was target vessel-related myocardial infarction. During the entire postoperative follow-up period, the control group had a target lesion failure event, with an incidence of 0.9% (1 / 113), and the type was cardiac death. During the entire postoperative follow-up period, the trial group had 13 cases of subject-related composite endpoint (PoCE) events, with an incidence of 11.8% (13 / 110), and the event types were any revascularization accounting for 10.0% (11 / 110), all-cause death accounting for 0.9% (1 / 110), and all myocardial infarction accounting for 0.9% (1 / 110). During the entire postoperative follow-up period, 16 PoCE events occurred in the control group, with an incidence of 14.2% (16 / 113). The event types were any revascularization accounting for 13.3% (15 / 113) and all-cause death accounting for 0.9% (1 / 113). No definite or possible thrombotic events occurred in the experimental group and the control group during the 12-month observation period after surgery. The results of the secondary endpoints based on the PPS set were similar to those of the FAS set, and the results of the PPS set supported the research results of the FAS set.

[0039] This shows that after the hydrophilic coating is mixed with the unabsorbed drug, the absorption effect of the drug can be enhanced, thereby improving the therapeutic effect of the vascular drug capsule.

[0040] It should be noted that the present invention relates to a coronary drug balloon with fast drug penetration. During operation, the catheter seat 1 is controlled, and the protective sleeve 14 end first enters the blood vessel from the puncture port, and slowly moves along the inner wall of the blood vessel to the treatment site. Then the inner tube 9, the balloon body 11, the distal outer tube 7, the proximal outer tube 5 and the hypotube 2 slowly enter the blood vessel. The drug coating 12 on the outer side of the balloon body 11 in the contracted state dissolves at a lower rate. When the balloon body 11 moves to the treatment site of the inner wall of the blood vessel, gas is filled into the pipes connected in sequence through the catheter seat 1, and the gas enters the balloon body 111 from the inner tube 9. The balloon body 11 expands to push the drug coating 12 open and fit it to the inner wall of the blood vessel. At this time, paclitaxel and the drug-loaded matrix are rapidly dissolved and absorbed by the vascular tissue. The unabsorbed paclitaxel flows backward under the action of the blood, and the hydrophilic coating 8 at the rear is dissolved and mixed with paclitaxel. The paclitaxel continues to be absorbed by the vascular tissue under the action of the hydrophilic coating, thereby improving the treatment effect of the vascular drug balloon.

[0041] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Any ordinary technician in the industry can smoothly implement the present invention as shown in the drawings and described above. However, any equivalent changes, modifications and evolutions made by technicians familiar with the profession without departing from the scope of the technical solution of the present invention using the technical content disclosed above are all equivalent embodiments of the present invention. At the same time, any equivalent changes, modifications and evolutions made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the technical solution of the present invention.

Claims

1. A coronary drug-eluting balloon with rapid drug penetration, characterized by: include A balloon body (11), wherein an inner tube (9) is provided inside the balloon body (11), and a developing ring (10) is provided on the outer periphery of the inner tube (9) and is located inside the balloon body (11); Both ends of the balloon body (11) are constructed in a conical shape, and the main part of the balloon body (11) is cylindrical. The outer periphery of the main part of the balloon body (11) is coated with a drug coating (12).

2. The coronary drug-eluting balloon with rapid drug penetration according to claim 1, characterized in that: The front end of the inner tube (9) extends to the outside of the balloon body (11), and the front end of the inner tube (9) is configured with a tip, on which a protective sleeve (14) is plugged, and the interior of the protective sleeve (14) is provided with a protective wire (13) extending to the inside of the inner tube (9).

3. The coronary drug-eluting balloon with rapid drug penetration according to claim 2, characterized in that: One end of the inner tube (9) away from the protective sleeve (14) is connected to a distal outer tube (7), and the outer periphery of the distal outer tube (7) is coated with a hydrophilic coating (8).

4. The coronary drug-eluting balloon with rapid drug penetration according to claim 3, characterized in that: The distal outer tube (7) is provided with a side port (6), and the end of the side port (6) away from the distal outer tube (7) is connected to the proximal outer tube (5), and the end of the proximal outer tube (5) is connected to a transition joint (4).

5. The coronary drug-eluting balloon with rapid drug penetration according to claim 4, characterized in that: The transition joint (4) is connected to a hypotube (2), and the outer circumference of the hypotube (2) is fitted with symmetrically arranged visual marks (3).

6. The coronary drug-eluting balloon with rapid drug penetration according to claim 5, characterized in that: The end of the hypotube (2) is connected to a catheter seat (1).

7. The coronary drug-eluting balloon with rapid drug penetration according to claim 1, characterized in that: The drug coating (12) is composed of a drug-carrying matrix and an active drug, and the drug-carrying matrix is ​​ioversol.

8. The coronary drug-eluting balloon with rapid drug penetration according to claim 7, characterized in that: The active drug is arranged on the surface of the drug-loaded matrix, and the content range is 2.5-3.0 μg / mm 2 .

9. The coronary drug-eluting balloon with rapid drug penetration according to claim 8, characterized in that: The active drug is selected as paclitaxel.

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