Recyclable drug delivery system and application thereofTechnical Field
The invention relates to a recyclable drug delivery system and application thereof, belonging to the field of medical appliances.
Background
Coronary atherosclerotic heart disease is a common cardiovascular disease, severely affecting people's health, unstable angina or myocardial infarction is a critical cause of death in ischemic heart disease. Percutaneous coronary intervention stent implantation therapy and recent drug balloon therapy are effective treatment modes of coronary heart disease. However, in-stent restenosis and re-implantation of the stent are currently a bottleneck in clinical treatment.
The drug balloon is an effective strategy for interventional therapy, and after the vascular stenosis is fully pre-expanded, the drug coated balloon can rapidly and uniformly deliver the antiproliferation drug to the vascular wall without leaving permanent implants. The current drug coatings are rapamycin derivatives and paclitaxel. Drug balloons, while avoiding permanent stent implantation, have many problems. For example, due to the inter-coronary wall lining and hematoma that may occur during the procedure, only remedial stent treatment can be used, the drug balloon uses a different drug coating, the paclitaxel coating absorbs rapidly, but requires approximately 60 seconds to keep the balloon inflated, alleviating the lining or hematoma, and longer balloon inflation times will obstruct normal blood flow. Rapamycin balloons are a potential drug balloon, potentially better improving therapeutic effects. Due to the poor tissue affinity of rapamycin, longer balloon expansion times are required, limiting the use of such drug balloons. The drug balloon can rapidly and uniformly deliver antiproliferative drugs to the vessel wall without leaving permanent inserts behind. Is currently applied to restenosis in stents and coronary artery primary lesions and peripheral vascular lesions. However, there are a number of disadvantages, such as vascular dissection, hematoma, elastic recoil, etc., leading to acute complications or affecting long-term prognosis, requiring more adequate pretreatment of lesions. Paclitaxel is currently a commonly used drug balloon coating due to its high tissue affinity and high release rate. Rapamycin derivative drug balloons have theoretically better therapeutic effects, but poor tissue affinity, and require longer vessel wall abutment time to promote drug release and absorption. The existing balloon drug delivery modes limit the use of such drugs.
The medicine coating stent is prepared by coating medicine on the surface of a conventional metal bare stent by a proper method, and the medicine is released under the condition of blood scouring to locally play a role. Current research focuses on stent materials, structural designs, and coating drugs and coating processes. Coating drugs are classified into five main classes according to pharmacological actions, namely antithrombotic drugs, anti-inflammatory drugs, anti-vascular smooth muscle proliferation drugs, anti-vascular smooth muscle migration drugs and endothelial cell healing promoting drugs. The clinical application is mainly based on anti-vascular smooth muscle proliferation drugs, such as rapamycin derivatives and paclitaxel. Cocktail-type drug cocktail may also occur in the future.
The design of the drug coating adaptive stent is different from the current classical DES in that when the drug coating of the polymer film is degraded in 6 months, the ring buckles among steel beams of the stent are also opened, so that the compliance of the stent in a blood vessel is enhanced after 6 months, the systolic and diastolic effects of arteries due to blood flow are not influenced, and the stent has potential clinical effectiveness.
The permanently implanted stent system is mainly a balloon expandable stent system, and comprises a stent and a delivery system. The stent is compressed and loaded on a balloon of a delivery system, and is released by the balloon after being delivered to a lesion site, and the stent is permanently left in the human body. The stent has a plurality of permanent implantation complications, such as late stent thrombosis, late stent adherence failure, late catch-up phenomenon, restenosis, stent fatigue fracture, poor long-term endothelial coverage and the like, and the stent coverage of the ultra-long vessel segment also has an influence on the vascular endothelial function.
The bioabsorbable stent is a stent system which adopts polymers such as polylactic acid and the like as a matrix, and achieves the aim of no implantation in intervention through three stages of blood transport reconstruction, stent degradation and absorption and vascular repair. At present, a domestic NeoVas degradable bracket is used in China. The metal degradable bracket is a metal bracket or an iron-based bracket which mainly comprises magnesium alloy and is provided with a rapamycin derivative coating, and the radial supporting durability is considered while the degradation time is kept for 12 months. The degradable stent still has the defects of late stent thrombosis, calcification of vessel wall, insufficient local supporting force, strict stent preservation and transportation requirements and the like.
The self-expansion bracket is a super-elastic bracket which is made of a nickel-titanium super-elastic alloy thin-wall pipe through laser precision engraving. The catheter reaches the lesion through the pressing holding type conveying catheter, and the catheter self-expands after the fixation is released to enable blood to be smooth and plays a supporting role on the lesion. The new generation of drug-coated self-expanding stents have completed clinical trials and show certain advantages, but fail to show that the operation is not simple due to the advantages of the traditional balloon-expandable stents.
The thrombus taking rack is mainly used in intracranial blood vessel and is one kind of self-expanding rack capable of being conveyed via micro catheter to the acutely occluded intracranial great blood vessel. The device is intended to engage the thrombus causing the large vessel occlusion and remove it from the circulation, thereby restoring intracranial blood flow. But the radial supporting force is poor, no guide wire is used for guiding, and the method is not suitable for coronary artery treatment.
From the above, it is clear that the interventional medical device for clinical coronary heart disease administration therapy needs to solve the technical problems that (1) the administration system is ensured to enter the guide catheter and the blood vessel along the guide wire, the guide wire can be continuously kept in the central cavity of the administration system, (2) the self-expanding bracket structure and the material design ensure safe release and recovery, (3) the self-expanding bracket structure and the material design ensure proper radial supporting force, (4) the bracket tectorial membrane is safe and reliable and cannot fall off and break in operation, (5) the tectorial membrane drug coating is reliably attached, does not fall off powder and is not adhered to the outer tube, (6) the tectorial membrane drug has proper tissue affinity, thereby being beneficial to release absorption and avoiding loss, (7) after the tectorial membrane bracket is released, the central cavity can enter the image catheter in the cavity along the guide wire, and (8) under special conditions, the inner cavity of the tectorial membrane bracket can enter other types of balloon or bracket for remote lesion therapy after the release.
CN113599032a discloses a retractable drug-coated stent, which comprises an inner tube, a middle tube and an outer tube, wherein the proximal ends of the inner tube, the middle tube and the outer tube are connected with a pushing device, the distal end of the inner tube is provided with a tip, the surface of the self-expanding stent is provided with a spike, the surface of the self-expanding stent is provided with a drug coating, the self-expanding stent is connected with the distal end of the middle tube, the self-expanding stent is in a furled state, and the self-expanding stent is also in an expanded state. The self-expanding stent provided by the invention has the advantages that the surface of the self-expanding stent is provided with the spines, so that calcification lesions and blood vessel intima can be penetrated, and the self-expanding stent enters the blood vessel media and adventitia for deep administration, and the drug utilization rate is improved; the drug coating stent can not remain in the body, and meanwhile, the mode can not block blood flow, can also control the administration time, and has simple and convenient whole operation process and easy operation. However, when the self-expanding stent spines penetrate calcified lesions, the spines are easy to scratch blood vessels when the stent is released and withdrawn if the hardness is too high, and when the spines are not enough in hardness, the self-expanding stent spines are difficult to penetrate calcified lesions and blood vessel intima, enter the blood vessel media and intima and are subjected to deep administration. The spike direction on the surface of the stent is vertical to the length direction of the stent, if calcification of a target blood vessel is serious in the release process of the stent along the length direction, the spike is difficult to penetrate calcification lesions, even the spike has the risk of falling off, and the spike structure is not suitable for coronary artery stenosis treatment due to the risk of scratching the blood vessel, and the structure limits the application of the stent.
In summary, the existing products have the problem of narrow application scenes, especially for coronary artery stenosis treatment, and no suitable and safe recoverable drug carrying system exists at present.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention aims at solving the problems of drug delivery and recovery of the existing product and providing a recoverable drug carrying system for solving the risk problems of hurting a blood vessel and the like during recovery, wherein the recoverable drug carrying system is based on a covered stent, and the drug carrying system is combined with a polymer composite drug carrying coating film through the covered stent, so that the drug can be released locally and slowly in the blood vessel after entering the blood vessel to position and release the stent. The covered stent is recovered after the drug is released, and no instrument is placed in the vessel cavity.
In view of the above, the present invention provides a recyclable drug delivery system that can be used in coronary vessels as well as peripheral vessels; the drug carrying system comprises a drug covered stent, a balloon, a tearable sheath and an outer tube; the stent 1 is connected with the balloon 2, the balloon part is preloaded in the stent, the drug-coated stent comprises a self-expanding stent and a drug-coated membrane, the self-expanding stent is of a porous structure, the porous surface is a carrier of the drug-coated membrane, the two ends of the self-expanding stent are open, the openings are gradually decreased along the axial length of the inclined openings, the main body part of the self-expanding stent is respectively arranged with the proximal end part of the self-expanding stent and the distal end part of the stent in an eccentric inclined opening manner, in other words, the cross section of the self-expanding stent is of a trapezoid shape, so that when the self-expanding stent is unfolded, the whole stent is of a polygon shape; the outer contour of each mesh unit of the self-expanding bracket is in a fish scale shape, each mesh unit is surrounded by connecting rods, connecting rods of adjacent mesh units are tightly attached, at the moment, the connecting rods of the adjacent mesh units are connected, in other words, the parts, which are equivalent to scales, of connecting fish bodies form the mesh units through independent connecting rods, are equivalent to the connection between scales, the mesh units are connected through the connecting rods, at the moment, the connecting rods provide axial pulling force in the radial compression process of the self-expanding bracket 101, so that the axial pulling force can smoothly enter the inner cavity of an outer tube like the fish scale, the reduction rate of the bracket, which is generated by the friction force with the outer tube, of the mesh units is compensated in the bracket release expansion process, the mesh units are sequentially arranged in the length direction and the circumferential direction through the connecting rods to form a net-shaped supporting body similar to fish scales, the intersection points of the adjacent mesh units of the fish scale-shaped porous structure are in a T shape, the adjacent two rows of mesh units are sequentially arranged in the radial length direction, in two adjacent lines, the mesh units of one line are arranged in a staggered way opposite to the other two adjacent mesh units, the staggered distance is 50-80% of the width of the mesh unit rods, each line of mesh units is formed by arranging a plurality of mesh units in sequence to be parallel to the axial direction of the self-expanding stent, the arrangement mode is that the mesh units of the first line and the mesh units of the second line are alternately arranged in the axial direction of the self-expanding stent, the mesh units are arranged in a staggered way perpendicular to the axial direction of the self-expanding stent, the mesh units of the two adjacent lines are aligned with the gaps of the adjacent mesh units of the two adjacent lines, and the mesh units of one line are opposite to the gaps of the two adjacent mesh units of the other line, so that the recyclable drug-coated stent is easier to compress and is more suitable for tiny blood vessels and is easier to be received in an outer tube.
Preferably, three angles A, B and C formed by the intersections of the T-shape, angle A ranges from 40 to 60, angle B ranges from 120 to 140, and angle C ranges from 170 to 180.
Preferably, the balloon is a post-expansion balloon, the post-expansion balloon is positioned in the inner cavity of the drug-coated stent, the distal end part of the drug-coated stent does not exceed the distal end part of the post-expansion balloon, and the proximal end part of the balloon does not exceed the proximal end part of the drug-coated stent.
Preferably, the drug-coated stent is compressed and then embedded in the tearable sheath, in other words, the drug-coated stent, the balloon and the tearable sheath are all embedded in the outer tube.
Preferably, one side X of the mesh unit is 2-6 mm in length.
Preferably, in order to further ensure the stability of the self-expanding stent 101 of the drug delivery system during expansion and contraction, the main body of the self-expanding stent is arranged concentrically with the proximal end of the stent and the distal end of the stent, so as to increase the contact area between the distal stent and the circumferential direction of the blood vessel, and facilitate better adherence of the stent.
More preferably, the main body part of the self-expanding stent and the proximal end part of the stent are in eccentric bevel design, which is beneficial to the recovery of the stent.
More preferably, in order to further secure recovery smoothness, the mesh unit areas of different regions of the self-expanding stent are different in size, the first mesh unit area < the second mesh unit 1 area < the third mesh unit 10114 area.
Preferably, the proximal end of the self-expanding stent is provided with a keel, the length direction of the keel is consistent with the length direction of the stent, and the length of the keel is the same as or similar to the length direction of the proximal end of the stent.
More preferably, the keel has a stem width of 0.2mm to 0.6mm and a length of 4 to 12mm.
As a preferred embodiment, the proximal end of the self-expanding stent is connected with a pushing rod, the proximal end of the self-expanding stent is welded with the pushing rod into a whole through a platinum iridium ring, the drug covered stent is pushed in the outer tube through the proximal end of the pushing rod, the pushing performance of the drug covered stent can be enhanced by the keels at the proximal end, deformation of the proximal end of the self-expanding stent due to overlarge pushing resistance is reduced, and meanwhile, the flexibility of the recyclable covered stent is guaranteed because only the keels are arranged at the proximal end part.
As a preferred embodiment, the three mesh units are arranged in the proximal keel portion of the self-expanding stent, the keels 103 and the first, second and third mesh units of the stent are arranged in sequence from the proximal end to the distal end, the first mesh unit 1 has an area 0.6-5.5mm2 greater than the second mesh unit, and the second mesh unit has an area 1.5-6.0mm2 greater than the third mesh unit.
More preferably, the outer surface of the push rod may be coated with a polymer material having a low coefficient of friction. The friction force of the pushing rod is reduced, and higher pushing performance is provided. The high molecular material with low friction coefficient comprises Polytetrafluoroethylene (PTFE) or polyethylene terephthalate (PET) plastic. As a preferred embodiment, the pushing rod adopts a design of gradually decreasing and gradually changing diameter, the diameter of the distal end of the pushing rod is small, and the diameter of the distal end is large. The small diameter push rod 5 ensures that it is soft enough, has a smaller radius of curvature, so that it better adapts to tortuous vessels, while the thicker diameter push rod provides a degree of stiffness to the distal end of the push, providing support strength for pushing within the catheter. The material of the alloy can be 304V stainless steel wire or nickel-titanium alloy.
Preferably, the self-expanding stent 101 is made of a metal material, mainly medical grade stainless steel such as 316L, 304, 306 and the like, NITI memory alloy material, mg-based alloy, titanium-based alloy, coCr-based alloy material such as L605, MP35N, phynox and the like, the self-expanding stent is made of nickel titanium NITI material, and the fish scale structure is made by a laser cutting process.
More preferably, the pusher bar may further comprise a support spring wound around a portion of the length of the pusher bar distal end of small diameter. The supporting spring plays a role in reinforcing the supporting strength of the small-diameter push rod to improve the conveyability of the push rod 5. The material of the alloy can be 304V stainless steel wire or alloy containing platinum.
More preferably, the push rod is provided with a twister at the proximal end, the twister is provided with a knob, the size of the inner cavity of the twister can be increased or reduced through the adjusting knob, the push rod is fixed in the inner cavity of the twister, and the twister can be operated at the proximal end to control the recyclable tectorial membrane bracket in the operation process, so that the use of instruments in the operation process is facilitated.
More preferably, the length of the keel is the same as or similar to the whole length of the self-expanding bracket, namely, the keel design can be carried out along the whole length direction of the bracket, the pushing performance of the self-expanding bracket can be further enhanced,
Preferably, the self-expanding stent of the drug-coated stent is provided with an upper drug-coated film, and the drug-coated film has a three-layer structure, namely an inner coating film, an outer coating film and a drug coating layer.
More preferably, an inner coating film and an outer coating film are arranged on the inner side and the outer side of the self-expanding stent, and the inner coating film and the outer coating film seal the films on the inner side and the outer side of the self-expanding stent together by a hot melting method to form the coating film stent with the self-expanding stent. As a preferred implementation mode, the inner coating film and the outer coating film are made of high polymer materials, the number of layers of the inner coating film is 1-10, and the number of layers of the outer coating film is 2-12.
Correspondingly, the polymer material is selected from ePTFE material, PU material, nylon material, etc., and the inner coating film and the outer coating film can be the same material or different materials. The coating material can also be TPU, PU, PTFE, pebax or nylon.
And the drug coating is added on the outer coating film to prepare a drug-coated film bracket, the drug coating carries out drug loading in modes of dip coating, spray coating and the like, wherein one or more layers can be formed by taking the first layer as a carrier, after the first layer is dried, the second layer and more than the second layer are combined with the carrier to carry out repeated drug loading, and the first layer and the second layer and more than the second layer can be respectively drug and carrier or crystal drug, and the drug is loaded layer by layer through dip coating or spray coating. In other words, the drug-coated stent comprises an inner coating, a self-expanding stent, an outer coating and a drug coating from inside to outside.
Further, the carrier may be liposome, dibutyl hydroxy toluene, polylactic acid-glycolic acid copolymer, polylactic acid, mineralized calcium phosphate, mixture of polylactic acid, mixture of the above polymers, polyfluoro derivatives, uygur display 370, and the main components are iopromide, acetyl tributyl citrate, magnesium stearate, medium chain triglyceride, polysorbate 20, sorbitol, iohexol, and ammonium salt of shellac.
The organic polymer material is mainly selected from polyethylene and its derivatives, polypropylene and its derivatives, polyfluoro derivatives, polylactic acid and its derivatives, mixture of polyethylene, polypropylene and polylactic acid and its derivatives, and also includes biostable material, biodegradable material and bioabsorbable material.
The drug material is mainly selected from rapamycin and derivatives thereof, taxol, and the drug loading density is preferably 1-7 mg/mm2;
The drug coating comprises a drug carrier and a drug for inhibiting endothelial proliferation. The drug coating is a system which combines a carrier with a drug by using a physical and chemical method, continuously and stably releases the drug in proper concentration in vivo under the actions of diffusion, permeation and the like, and finally enables the drug to exert the maximum efficacy.
Preferably, the tearable sheath comprises a distal flexible member and a proximal rigid member, wherein the distal flexible member can be torn for stent preassembly, the proximal rigid member cannot be torn for providing an instrument supporting effect, the flexible member and the rigid member are connected into a unified whole through welding or hot melting technology for integral transportation and retraction, and the tearable sheath can be torn for releasing the stent through the expansion effect of balloon back expansion.
More preferably, the distal flexible member is a single-layer plastic tube and is cylindrical, the two sides of the tube body of the flexible member are respectively preset with symmetrically distributed tearable indentation lines, the indentation lines are in radial length direction, and the two sides of the tube body of the flexible member are respectively preset with symmetrically distributed tearable indentation lines, and the indentation lines are in radial length direction.
In the preferred embodiment, the tube body of the tearable sheath is provided with a plurality of porous structures which are arranged in a staggered manner and are uniform to form the indentation line, at this time, the porous structure of the indentation line is divided into a middle part, a distal part and a proximal part, and the size of the hole of the middle part in the length direction is greater than the size of the holes of the proximal end and the distal end, so that the design is favorable for tearing in vivo.
As a preferred embodiment, the rigid part is a single-layer plastic pipe, the rigid part is free of holes and indentation lines, and is connected with the flexible part into a whole through welding or hot melting technology, and the unified integral structure is convenient for the use of the instrument.
More preferably, the recyclable drug carrying system is further provided with a Y valve, and the Y valve fixedly connects the outer tube, the tearable sheath, the drug covered stent and the rear expanding balloon, so that the relative sliding among instruments can be reduced, and the accurate positioning is realized. In other words, the tearable sheath is sleeved on the drug covered stent, the drug covered stent is sleeved on the back expanding balloon, the balloon guide wire cavity can be used for guiding wires, the Y valve can adjust the size of an inner hole of the Y valve through an adjusting nut, the recyclable covered drug stent and the back expanding balloon penetrate through the inner hole of the Y valve to fix the push rod part of the Y valve, the Y valve can adjust the size of the inner hole of the Y valve through the adjusting nut, the recyclable covered drug stent and the back expanding balloon penetrate through the inner hole of the valve to fix the push rod part of the back expanding balloon, the far-end development of the stent does not exceed the far-end development of the back expanding balloon, and the far-end development of the outer tube does not exceed the far-end development of the back expanding balloon.
It is a further object of the present invention to provide the use of any of the above-described recyclable drug delivery systems as drug delivery systems for the treatment of coronary heart disease.
Terminology:
percutaneous transluminal coronary angioplasty, which is to send a balloon catheter to a coronary artery stenosis by femoral artery puncture, expand the balloon catheter under pressure to increase the inner diameter of a blood vessel and improve myocardial blood supply.
Interventional operation, namely, interventional therapy is a minimally invasive therapy by utilizing modern high-tech means, namely, under the guidance of medical imaging equipment, special precise instruments such as a catheter, a guide wire and the like are introduced into a human body to diagnose and locally treat in vivo pathological conditions.
The self-expanding support is a super-elastic support which is made of a nickel-titanium super-elastic alloy thin-wall tube through laser precise engraving. The catheter reaches the lesion through the pressing holding type conveying catheter, and the catheter self-expands after the fixation is released to enable blood to be smooth and plays a supporting role on the lesion.
The coated stent refers to a stent coated with special membranous materials (polytetrafluoroethylene, terylene, polyurethane and the like) on a metal stent. Not only maintains the function of the metal bracket, but also has the characteristic of membranous material.
The thrombus taking rack belongs to a recyclable rack, and thrombus can be embedded into the mesh structure of the rack after the rack is placed in a blocked blood vessel, and the thrombus and the rack can be taken out of the body together.
The stent shortening rate is that the axial length of the stent which is unfolded in the lumen of a human body is denoted as L1, the axial length of the stent in the compressed state of the outer tube is denoted as L2, and generally L1 is smaller than L2, so that the ratio of the difference between the two lengths to L2 is called the stent shortening rate.
Compared with the prior art, the invention realizes the relative technical breakthrough of rapid, safe and efficient drug administration in interventional operation for the first time without damaging adjacent tissues, especially the technical breakthrough for coronary heart disease treatment. Compared with the existing various drug delivery treatment systems, the recyclable drug delivery system has the following advantages:
1. Aiming at the contrast agent, through the breach with the diameter of more than or equal to 1mm, the contrast agent leaks into Coronary Artery Perforation (CAP) of pericardium (IIIA type), heart chamber or coronary vein (IIIB type) in a jet mode, and the breach is larger, so that the success rate of plugging is improved, the recyclable drug delivery system provided by the invention can be used as a first-choice implantation tectorial membrane bracket;
2. CAP treatment may be performed;
3. The operation is safe and stable, simple and convenient;
Drawings
FIG. 1 is a schematic diagram of a recyclable drug delivery system provided by the present invention;
FIG. 2 is a schematic illustration of a drug-coated stent of the recyclable drug delivery system provided by the present invention after expansion;
FIG. 3 is a cross-sectional view of a drug-coated stent of the recyclable drug delivery system provided by the present invention after expansion;
FIG. 4 is a view showing the state of the drug-coated stent of the recyclable drug delivery system
FIG. 5 is a view showing the expanded state of the drug-coated stent of the recyclable drug delivery system provided by the present invention;
FIG. 6 is an enlarged view of a portion of a mesh unit of a drug-coated stent of a recyclable drug delivery system provided by the present invention;
FIG. 7 is a schematic view of a keel of a drug-coated stent of the recyclable drug delivery system provided by the present invention;
FIG. 8 is a graph of the drug-coated stent of the recyclable drug delivery system provided by the present invention at rest;
FIG. 9 is a diagram of the motion profile of a drug-coated stent of the recyclable drug delivery system provided by the present invention;
FIG. 10 is a schematic view of a full keel of a drug-coated stent of the recyclable drug delivery system provided by the present invention;
FIG. 11 is an enlarged view of a unit section of a drug-coated stent of the recyclable drug delivery system provided by the present invention;
FIG. 12 is an enlarged view of a portion of a drug-coated stent of the recyclable drug delivery system provided by the present invention after deployment;
FIG. 13 is a schematic view of a recyclable drug delivery system provided by the present invention in a drug-coated stent deployed state;
FIG. 14 is a schematic illustration of a split sheath of a recyclable drug delivery system provided in accordance with the present invention;
FIG. 15 is a schematic view of the creasing lines of the tear-away sheath of the recyclable drug delivery system provided in the present invention;
FIG. 16 is a schematic view of a recyclable drug delivery system provided in accordance with the present invention in a blood vessel;
FIG. 17 is an image of a recyclable drug delivery system provided in the present invention within a blood vessel;
FIG. 18 is a graph showing the data of drug content under the action of the drug delivery system in animal experiments with the recyclable drug delivery system provided by the present invention;
In the figure, ff-dynamic friction force, F-static friction force, ft-supporting force, F1-radial expansion component force, F2-axial compression force and T-pulling force.
Detailed Description
The recyclable drug delivery system and system provided by the present invention are described in further detail and completeness below in connection with the examples. The following examples are illustrative only and are not to be construed as limiting the invention.
Because the placement position of the product can be changed at will, the terms such as upper, lower, left, right, front, back and the like in the application only represent relative positional relationship and are not used for limiting absolute positional relationship. In addition, the "front end" in the present application means an end far from the operator, and the "rear end" means an end near the operator.
All directional indications (such as up, down, left, right, front, rear) in the embodiments of the present application are merely used to explain the relative positional relationship, movement conditions, etc. between the components in a certain posture (as shown in the drawings), and if the certain posture is changed, the directional indication is changed accordingly.
The description of "first," "second," etc. in this disclosure is for descriptive purposes only and is not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In addition, the technical solutions of the embodiments may be combined with each other, but it is necessary to base that the technical solutions can be realized by those skilled in the art, and when the technical solutions are contradictory or cannot be realized, the technical solutions should be considered that the combination does not exist and is not within the scope of protection claimed by the present application.
A flowchart is used in the present application to describe the operations performed by a system according to embodiments of the present application. It should be understood that the operations before or after the flow chart are not necessarily performed in exact order. Rather, the steps may be processed in reverse order or simultaneously. Also, other operations may be added to or removed from these processes.
Example 1
FIG. 1 is a schematic diagram of a recyclable drug delivery system provided by the present invention, which can be used in coronary vessels as well as peripheral vessels. As shown in figure 1, the drug-carrying system is based on a self-expanding stent, and the corresponding drug-carrying system comprises a drug-coated stent 1, a balloon 2, a tearable sheath 3 and an outer tube 4, wherein the stent 1 is connected with the balloon 2, the balloon 2 is partially pre-installed in the stent 1, the embodiment adopts a post-expanding balloon, the post-expanding balloon provides radial supporting force to ensure sufficient adherence of the drug-coated stent, the post-expanding balloon is positioned in an inner cavity of the drug-coated stent, the distal end part of the drug-coated stent is not more than the distal end part of the post-expanding balloon, and the proximal end part of the balloon is not more than the proximal end part of the drug-coated stent. The drug-coated stent 1 is compressed and then is arranged in the tearable sheath 3, in other words, the drug-coated stent 1, the balloon 2 and the tearable sheath 3 are all arranged in the outer tube 4.
The prior various recoverable brackets or drug brackets adopting mesh structures have the same problem that radial shrinkage force is generated due to the reduction of the height of the mesh units in the compression process of the mesh units, the bracket is required to be recovered into the outer tube by a core wire at the proximal end in the recovery process of the bracket, and the friction force between the bracket and the outer tube is increased due to overlarge radial compression force at the moment, so that the operation risk is increased. In the expansion process of the stent, the outer tube is required to be withdrawn, at the moment, the height of the mesh unit is increased to generate radial expansion force, the stent can be gradually expanded to a target blood vessel due to the radial force of the stent, the stent is attached to the blood vessel, the outer tube withdrawal force can be excessively large if the radial expansion force is excessively large, the clinical use risk is increased, and the stent with the excessively small radial expansion force is easily shifted, so that the attachment performance of the stent is influenced. Therefore, the design structure of the support is required to ensure proper radial force of the support and better conveying performance.
Aiming at a plurality of defects of the existing product, the self-expandable stent 101 of the drug-coated stent 1 is manufactured into a porous structure with unique structural layout, the porous surface can be used as a carrier of the drug-coated film, the drug-coated stent is obtained by combining the self-expandable stent 101 and the drug-coated film 102, fig. 2 is a schematic diagram of the drug-coated stent after expansion, as shown in fig. 2, the two ends of the drug-coated stent 1 are open and the openings are inclined, in other words, the length of the porous self-expandable stent 101 along the axial direction is reduced, the main body part 1012 of the self-expandable stent 101 is respectively arranged with the proximal part 1013 and the distal part 1014 of the self-expandable stent 101 in an eccentric inclined way, as shown in fig. 3, the section of the self-expandable stent 101 is trapezoid. Fig. 4 and 5 are expanded state diagrams of the stent, as shown in fig. 4 and 5, the stent is polygonal as a whole, wherein the outer contour of each mesh unit 1011 of the self-expandable stent 101 is shaped like a fish scale as a whole, each mesh unit 1011 is formed by surrounding the connecting rod 10111, the connecting rods 10111 of adjacent mesh units 1011 are tightly attached, at this time, the connecting rods 10111 of adjacent mesh units 1011 are connected, the parts corresponding to scales connecting the fish bodies form the mesh units 1011 through the independent connecting rods 10111, the connection corresponding to scales connects the mesh units 1011 through the connecting rods 10111, axial pulling force can be provided in the radial compression process of the self-expandable stent 101, the axial pulling force can smoothly enter the inner cavity of the outer tube 4 like a fish scale, the stent shrinkage rate generated by the mesh units 1011 is compensated in the stent release expansion process of the outer tube 4 is reduced, and the mesh units 1011 are sequentially arranged in the length direction and the circumferential direction through the connecting rods 10111, so that the net-shaped supporting body like a fish scale is formed. Unlike available cross or Y-shaped cross points, the fish scale structure has adjacent cells in T-shape, i.e. two adjacent rows of cells are arranged successively, and one cell is staggered in two adjacent rows along the length direction to the other two adjacent cells, with the staggered distance being 50-80% of the width of the cell. Fig. 6 is a partial enlarged view of a part of the adjacent mesh unit 1011, as shown in fig. 6, the angle a ranges from 40 ° to 60 °, the angle B ranges from 120 ° to 140 °, and the angle C ranges from 170 ° to 180 °. In addition, the length X of the mesh units is 2-6 mm, and in two adjacent rows of the mesh units 1011, the mesh unit 1011 of one row faces the gap of the two adjacent mesh units 1011 of the other row, so that the recyclable tectorial membrane bracket is easier to compress, more suitable for tiny blood vessels and easier to be taken in the outer tube 4. Each row of mesh units 1011 are sequentially arranged in parallel with the axial direction of the self-expanding stent 101 by a plurality of mesh units 1011 in such a manner that the first row of mesh units 1011 and the second row of mesh units 1011 are alternately arranged in the axial direction of the self-expanding stent, are arranged in a staggered manner in the direction perpendicular to the axial direction of the self-expanding stent, and the mesh units 1011 are aligned with the gaps of the adjacent mesh units 1011 in the direction perpendicular to the axial direction of the self-expanding stent, such an arrangement is advantageous in that the mesh wires on one circumference of each section of the self-expanding stent and the cross section thereof are uniformly distributed, thereby being capable of providing uniform supporting force and having a better expanding effect. Compared with a common quadrilateral structure, the fish scale structure can enable the support mesh unit 1011 to form a coaxial structure in the length direction and the circumferential direction, so that the mesh arrangement of the main body 1012 of the support is smoother, meanwhile, the macromolecule membrane on the surface of the support is smoother, the defect of macromolecule membrane invagination is reduced, meanwhile, due to the limitation of the process, the structural design of the common quadrilateral mesh unit, the stability of the support is poorer, the width and the wall thickness of the support rod are required to be larger, the area of the mesh unit is required to be increased due to the increase of the rod width of the support, the radial expansion force difference of the area of the too large mesh unit is required to be increased for a small support suitable for coronary artery, the design of the fish scale structure can realize the wall thickness of the support with small rod width and small support, even smaller mesh structure is beneficial to improving the flexibility and the pushing property of the support, meanwhile, the contact area of the support and the macromolecule membrane is increased, the thickness difference of the rod width and the macromolecule membrane is reduced, and the macromolecule membrane is also called as extremely bad, and the macromolecule membrane is more close to the outer surface of the support, so that the macromolecule membrane is better in contact with a vascular coating and the drug absorption rate is better. In addition, mesh units 1011 are arranged in sequence like a fish scale shape, which can effectively reduce friction force between instruments and is helpful for improving conductivity of the stent in blood vessels and flexibility when passing through curved blood vessels.
In order to further realize the stability of the self-expanding stent 101 of the drug delivery system of the present application during expansion and contraction, the main body 1012 of the self-expanding stent 101 may be disposed concentric with the proximal stent part 1013 and the distal stent part 1014, respectively, so as to increase the contact area between the distal stent and the blood vessel in the circumferential direction, thereby facilitating better adhesion of the stent, and the main body 1012 of the stent and the proximal stent part 1013 are designed with eccentric bevel, thereby facilitating recovery of the stent.
In addition, the self-expanding bracket 101 is provided with a keel 103 at the proximal end, as shown in FIG. 7, the width of the keel is 0.2 mm-0.6 mm, the length direction of the keel is consistent with the length direction of the bracket, the length is preferably the same as or similar to the length direction of the proximal end 1013 of the bracket, and the length is 4-12 mm. As a preferred embodiment, the proximal end of the self-expandable stent 101 is welded with the pushing rod 104 through a platinum iridium ring, the drug-coated stent 1 is pushed in the outer tube 4 through the proximal end of the pushing rod 104, the pushing performance of the drug-coated stent 1 can be enhanced by the keel 103 at the proximal end, the deformation of the proximal end of the self-expandable stent 101 due to overlarge pushing resistance is reduced, and meanwhile, the flexibility of the recyclable coated stent is ensured because only the keel 103 is arranged at the proximal end.
It should be noted that, in order to further ensure the recovery smoothness, the mesh units in different areas of the self-expandable stent 101 have different sizes, and fig. 12 is a partially enlarged view of the stent after deployment, as shown in fig. 12, specifically, the area of the first mesh unit 10112 < the area of the second mesh unit 10113 < the area of the third mesh unit 10114, and since the mesh units 1011 of these three parts are at the portion of the proximal keel 103 of the self-expandable stent 101, the area of the first mesh unit 10112 is 0.6-5.5mm2 mm larger than the area of the second mesh unit 10113, and the area of the second mesh unit 10113 is (1.5-6.0) mm2 larger than the area of the third mesh unit 10114. The keels 103 are sequentially arranged with the first mesh unit 10112, the second mesh unit 10113 and the third partial mesh unit 10114 of the stent from the proximal end to the distal end, so that the bearing capacity of the stent in the radial direction is improved, the maximum strain in the compression process is effectively reduced, and the compressibility of the stent is improved, meanwhile, the length of the keels 103 is designed to be consistent with the length of the proximal end of the stent, so that the stent still has better flexibility in a blood vessel, the support property of the proximal end of the stent and the rigidity against deformation are enhanced, and the conveying performance of the outer tube 4 can be enhanced. In addition, the proximal end of the self-expanding bracket 101 is connected with a pushing rod 5, because the proximal end of the bracket is designed to be an eccentric bevel, force is excessively dispersed in the pushing process of the pushing rod 5 to enable the proximal mesh rod to be deformed widely, and the pushing force of the core wires can be mostly concentrated to the position of the keels through the design of connecting different mesh areas, so that the deformation of the bracket is reduced, and meanwhile, the pushing force of the bracket is reduced. Before use, the recyclable covered stent is required to be loaded in the outer tube 4, the keel 103, the first part of mesh, the second part of mesh and the third part of mesh of the stent are sequentially compressed under the action of the pulling force of the pushing rod 5, the outer tube 4 and the recyclable covered stent are conveyed to a lesion position during operation, the outer tube 4 is withdrawn, the stent can be self-expanded to the original diameter, and finally the recyclable covered stent is recycled by the outer tube 4. The attachment of the keels 103 improves the stability of the stent and at the same time improves the anchoring of the stent in the vessel, reducing the risk of its displacement.
When the stent design of the present application is adopted to recover to DE, when the push rod 5 applies an axial pulling force T to the self-expanding stent 101, due to the double designs of the unique fish scale mesh units and the meshes with different sizes, part of the mesh units can be compressed into the outer tube 4, the other part of the mesh units expands outside the outer tube 4, a horizontal dynamic friction force Ff can be generated, the mesh units 1011 contact with the outer tube 4, a pressure Ft perpendicular to the mesh units 1011 can be generated, the supporting force Ft is decomposed into a radial expansion component force f1= Ftsin & lt a and an axial compression force f2= Ftcos & lt a, when T > ff+f2, the stent can generate a relative motion in the inner cavity of the outer tube 4, and when the self-expanding stent 101 is stationary, a friction force f=f2 can be generated.
The proximal end of the drug-coated stent 1 is connected with the distal end of the push rod 5, and a developing element is arranged at the connecting part, and the developing element in the embodiment adopts a noble metal developing point, so that the developing property is strong, and the position of the stent can be determined by an operator in an operation. The pushing rod 4 is made of nickel-titanium alloy, stainless steel wire and the like, so that the pushing rod has good flexibility and rebound resilience, and is convenient for pushing the drug covered stent system in a bent blood vessel. Further, the outer surface of the pushing rod 5 may be coated with a polymer material with a low friction coefficient. The friction force of the pushing rod 5 is reduced, and higher pushing performance is provided. The high molecular material with low friction coefficient comprises Polytetrafluoroethylene (PTFE) or polyethylene terephthalate (PET) plastic, and Polytetrafluoroethylene (PTFE) is adopted in the embodiment. The push rod 5 adopts the design of gradually decreasing and gradually changing diameter, and the diameter of the distal end of the push rod 5 is small, and the diameter of the distal end far away from the push rod is large. The small diameter push rod 5 ensures that it is soft enough, has a smaller radius of curvature, so that it better adapts to tortuous vessels, while the thicker diameter push rod 5 provides a degree of rigidity to the distal end of the push, providing support strength for pushing within the catheter. The material of the alloy can be 304V stainless steel wire or nickel-titanium alloy. The push rod 5 may also include a support spring wound around a portion of the length of the push rod distal end of small diameter. The supporting spring plays a role in reinforcing the supporting strength of the small-diameter push rod to improve the conveyability of the push rod 5. The material of the alloy can be 304V stainless steel wire or alloy containing platinum. In addition, as shown in fig. 2, the proximal end of the pushing rod 5 is provided with a twister 6, the twister 6 is provided with a knob, the size of the inner cavity of the twister can be increased or reduced through the adjusting knob, the pushing rod 5 is fixed in the inner cavity of the twister, in the operation process, the twister 6 can be operated at the proximal end to control the recyclable film covered stent, and the use of instruments in the operation process is facilitated.
In addition, the keel 103 may be disposed along the entire length of the self-expanding stent 101, i.e., the keel 103' may be designed along the entire stent length, so as to further enhance the pushing performance of the self-expanding stent 101, as shown in fig. 10. The length of the keel 103 can also be the total length of the proximal portion 1012, the main body portion 1013 and the distal portion 1014 of the self-expanding stent, the length of which varies with the length of the stent, and this structure adds the reinforcing ribs to the entire length of the self-expanding stent, reduces the pushing resistance of the recyclable stent graft in the outer tube 4, and increases the radial support force of the stent.
In this embodiment, the self-expanding stent is made of nickel titanium NITI, and the above-mentioned fish scale structure is made by laser cutting process.
The self-expandable stent 101 of the drug-coated stent 1 is provided with an upper drug-coated film 102, and the drug-coated film 102 has a three-layer structure, namely an inner coating film 1021, an outer coating film 1022 and a drug coating 1023. The inner and outer side of the self-expandable stent 101 are provided with an inner coating film 1021 and an outer coating film 1022, and the inner coating film 1021 and the outer coating film 1022 seal the films on the inner and outer sides of the self-expandable stent 101 together by a hot-melting method of a high-temperature resistant metal core rod to form a coating film stent with the self-expandable stent 101. In this embodiment, the inner and outer coating films 1021 and 1022 are made of ePTFE, the number of layers of the inner coating film 1021 is 1-10, and the number of layers of the outer coating film 1022 is 2-12. Still further, a drug coating 1023 is added to the outer coating 1022 to obtain the drug-coated stent 1, wherein the drug in this embodiment is rapamycin and the carrier is urea. The carrier can protect rapamycin, reduce drug delivery loss, and simultaneously can control the release speed of drugs through different carriers, thereby achieving the therapeutic effect. The medicine coating can be used for carrying medicine in a dip-coating mode, a spray-coating mode and the like, wherein one or more layers can be formed by taking a first layer as a carrier, after the first layer is dried, the second layer and more than the second layer are combined with the carrier for carrying medicine repeatedly, or the first layer and the second layer and more than the first layer are both medicines and the carrier or crystal medicines, and the medicine is carried layer by layer through dip-coating or spray-coating. The present embodiment is not limited thereto. Fig. 11 is an enlarged sectional view of the unit of the drug-coated stent of the present embodiment, and as shown in fig. 11, the drug-coated stent 1 is composed of an inner coating 1021, a self-expanding stent 101, an outer coating 1022 and a drug coating 1023 in this order from the inside to the outside.
The drug coating is quick release, and the drug quickly permeates into the lesion blood vessel in the stent expanding process, so that the purpose of quick treatment is realized. The medical urea not only prevents thrombosis and restenosis in the stent, but also has the function of a drug carrier, can smoothly carry the drug to a lesion part, and reduces the drug loss in the drug delivery process. Simultaneously, the medicine is dissolved in blood in the stent expanding process, so that the medicine is directly contacted with and absorbed by the diseased vessel, and the aim of rapid treatment is fulfilled. In this example, rapamycin and urea are mixed in a ratio of 1:7, 10ml of methanol solution is added, and the mixture is subjected to ultrasonic vibration for 1 hour. After the mixed solution is filtered by using a 0.35um filter head, the support is fixed under the nozzle, the support can rotate at a constant speed in the spraying process, the mixed solution is continuously sprayed out through the nozzle of the spraying machine, and the mixed solution is repeatedly sprayed on the surface of the coating film outside the support layer by layer.
As shown in FIG. 1, the distal end of the drug-coated stent 1 is further provided with a distal end development 104, in this embodiment, the distal end development 104 is a development filament, the development filament is wound at the head end of the matrix stent and is in a spring-like arrangement, a soft spring form is adopted, damage to a blood vessel caused by direct ejection of the stent on the blood vessel wall due to misoperation when an instrument is discharged out of the catheter can be avoided, the trafficability of the drug-coated stent is increased, the development filament is opaque to X-rays, a clinician can monitor the X-ray opaque filament through a angiography device such as DSA (digital subtraction angiography), the position of the filament can be checked, the state of complete opening and compression of the drug-coated stent can be known, and the development filament can be made of platinum-tungsten alloy. The proximal end of the drug-coated stent is provided with a proximal end development 105, the proximal end development 105 and the distal end development 104 of the drug-coated stent are used for the position of the stent in a blood vessel during operation, in this embodiment, the proximal end development 105 adopts a platinum iridium ring, the platinum iridium ring is in a cylindrical annular structure, and the self-expanding stent, the push rod and the platinum iridium ring are welded and fixed through a brazing process.
The traditional recoverable stent is preloaded in the loader before operation, the stent is conveyed to the target vascular position through the microcatheter during operation, the operation process is complex, relative displacement is easy to occur between instruments in the operation process, and the position of the instruments needs to be confirmed by repeated radiography. As described above, when the stent graft of the present application is pre-assembled in the outer tube 4 in vitro, the stent graft 1 may be fixed in the outer tube, and the outer diameter of the self-expandable stent 101 is larger than the size of the inner lumen of the outer tube, so that the stent graft may be fixed in the outer tube by pre-assembling the stent graft in the inner lumen of the outer tube. The device has the advantages that no relative displacement of the device can be generated under the action of external force pulling, the far-end development 104 of the film covered medicament stent is flush with the far-end development 401 of the outer tube, the position of the recyclable film covered stent can be determined in vitro to assemble, the positioning function can be realized in the operation process, the position of the stent can be determined according to the position of the far end of the extension catheter, the precise positioning and releasing of the stent can be realized, and on the other hand, the recyclable film covered stent is preloaded on the outer tube, the steps of mechanical operation are reduced, and the operation is convenient.
It should be noted that the conventional tearable sheath is torn in vitro, and the handle is required to be pulled to the outer side by two hands, so that the plastic pipe with the indentation line is torn, and only a single tearable circular pipe part is arranged in the length direction. The invention provides a tearable sheath 3 which can be torn in a body, wherein fig. 14 is a schematic diagram of the tearable sheath, fig. 15 is a schematic diagram of an indentation line, the tearable sheath 3 comprises a distal flexible part and a proximal rigid part, the distal flexible part can be torn for preassembling a bracket, the proximal rigid part can not be torn for providing an instrument supporting effect, the flexible part and the rigid part are connected into a unified whole through welding or hot melting technology, the whole can be conveyed and retracted, and the tearable sheath can be torn for releasing the bracket through the expansion effect of the balloon after the balloon is expanded. The flexible distal part is a single-layer plastic pipe and is cylindrical, two sides of the pipe body of the flexible part are respectively preset with symmetrical tearable indentation lines 301, the indentation lines are in a radial length direction, two sides of the pipe body of the flexible part are respectively preset with symmetrical tearable indentation lines 30111 and 30112, the indentation lines are in a radial length direction, the pipe body 302 of the tearable sheath 3 is provided with a plurality of staggered uniform porous structures, namely the indentation lines 301, at the moment, the porous structure of the indentation lines is divided into a middle part 3011, a distal part 3012 and a proximal part 3013, the size of the holes of the middle part in the length direction is greater than the size of the proximal end and the distal end holes, the design is favorable for tearing in vivo, the rigid part is a single-layer plastic pipe, the rigid part is free of holes and the indentation lines, and is connected with the flexible part into a whole through welding or hot melting technology, and the uniform integral structure is convenient for the use of the instrument. Before operation, the outer diameter of the stent is compressed to be smaller than the inner cavity of the flexible piece of the tearable sheath 3, the inner diameter of the cavity is required to be determined according to the specification and model of the stent, the minimum inner diameter of the cavity is 1.32mm, and the maximum inner diameter of the cavity is 2.64mm. The method comprises the steps of pre-installing a film-covered medicine support in a tearable sheath 3 sheath, in the operation process, withdrawing an internal outer tube 4 to release the tearable sheath 3 to a target vessel position, expanding a back-expanded balloon pre-installed in the inner cavity of the support, starting tearing off an indentation line 301 of a flexible part of the tearable sheath 3 from a middle part under the expansion action of the back-expanded balloon by the expansion action of the balloon and the radial expansion force of the support, then gradually diffusing the tearing off area to a proximal end part and a distal end part until the indentation line 301 is fully opened, and realizing the tearing off of a sleeve at a perforation position, wherein when the support is expanded to a normal or fully expanded diameter, the sleeve is continuously torn off at the perforation position in a zipper mode until the support is fully released, and the structure does not cause foreign matters to fall off.
After the device comprising the outer tube 4 and the stent graft and the post-expansion balloon is positioned, the stent may be retracted or advanced if the self-expanding stent 101 is released by retracting the outer tube 4. The stent is pre-installed in the tearable sheath 3, the recyclable drug carrying system is pressurized by the post-expansion balloon after reaching the target vessel position, the stent tears the flexible part of the tearable sheath 3 wrapping the stent under the expansion force of the post-expansion balloon and the radial expansion force of the stent, and the whole tearable sheath 3 is withdrawn from the body after the post-expansion balloon is withdrawn and pressed, so that the precise positioning of the stent can be facilitated. The tearable sheath 3 can reduce the transmission loss of the drug covered stent in the body, and after the system is transmitted to the target lesion position, the tearable sheath 3 in the body is torn by the back-withdrawn outer tube 4 and the balloon is expanded, so that the stent is positioned more accurately.
In the conventional implanted stent, since the stent is rapidly expanded to the vessel wall after being released from the outer tube 4, if the stent is provided with the internal tearable sheath in a matched manner, when the stent rapidly expands, particularly the conventional internal tearable sheath, the tearable sheath 3 is often trapped between the stent and the vessel wall due to untimely withdrawal, and can be withdrawn by needing great force, the endothelium is easily damaged by overlarge friction force, even an interlayer is caused, and in addition, the torn tube is easily broken by foreign matters after being torn, so that the operation risk is caused. The recoverable tectorial membrane stent has small radial force, and the radial supporting force is required to be provided for ensuring enough adherence by the back expansion of the back expansion balloon, so that the radial force between the stent and a blood vessel can be reduced by releasing the pressure of the balloon after the tearable sheath 3 is torn by the expansion action of the back expansion balloon, and the tearable sheath 3 is withdrawn, so that the friction force is small in the operation process and the endothelium is not damaged.
The drug-coated stent is loaded in the inner cavity of the tearable sheath 3, can better protect the drug coating on the stent in the process of external assembly, reduce the scratch between the stent and the instrument and the transmission loss, and can reduce the scouring action of the drug coating of the stent in blood and improve the absorption efficiency of the vascular drug due to the wrapping of the tearable sheath 3 in the process of internal system transmission.
Fig. 13 is a schematic view of the drug delivery system in a stent deployment state, as shown in fig. 13, in this case, the drug delivery system is sequentially sleeved with the rear expanding balloon 2, the drug covered stent 1, the outer tube 4 and the guide wire 8 from inside to outside. The stent 1 is sleeved on the rear expanding balloon 2, a guide wire 8 can be led through a guide wire cavity of the balloon 2, the guide wire 8 is pre-installed in a guide tube of the rear expanding balloon 2, the stent 1 is in a furled state and an expanded state, the stent 1 is compressed in the outer tube 4 in the furled state, at the moment, the distal end development 401 of the outer tube is flush with the distal end development spring 104 of the stent, the distal end development spring 104 of the stent is flush with the distal end development 301 of the rear expanding balloon, the distal end development 401 of the outer tube, the distal end development 104 of the stent and the distal end development 201 of the rear expanding balloon are kept at a relative position, the self-expanding stent 101 used at present can be recycled into the guide tube before being completely released, the guide tube can not be recycled after being completely released, but the two stents can be repeatedly released and recycled, the guide wire does not enter the instrument at any time, and the guide wire in the central cavity is very unsafe for the intracoronary operation, the rapid exchange along the guide wire which is formed in a manner of a rapid-expanding balloon or a short micro-catheter which is pre-arranged in the film stent as a loader is used as a loader, and the center wire system is always ensured in the central system. In the expanded state, the outer tube 4 is retracted, and the stent 1 can expand by the radial force of the stent itself to adhere to the blood vessel. The stent surface is provided with an outer coating 1022, the outer coating 1022 is provided with a drug coating 1023, the stent is in a furled state before reaching a lesion position, the distal end development 401 of the outer tube is contacted with the tip of a distal development spring 104 of the stent, after the drug coating stent reaches the lesion position along a guide wire 8, the outer tube 4 is retracted to enable the stent 1 and the outer tube 4 to slide relatively, the stent 1 is gradually released from the outer tube 4 in the process of sliding the outer tube 4 and the stent 1 relatively, the stent 1 is switched from the furled state to an expanded state, at the moment, the stent 1 is separated from the limit of the outer tube 4, self-expands until a target lesion is abutted against a vascular wall and the drug is absorbed by the vascular wall, then the post-expansion balloon 2 is inflated to ensure the adhesion of the stent, the post-expansion balloon is alternately expanded for 5 times, the interval is 30-60s, and the aim of enhancing the adhesion of the stent and the absorption of the drug coating by the vascular endothelial is promoted. Along with the increase of the attaching time of the stent 1 and the vascular wall, the medicine is continuously absorbed by the blood vessel and is diffused to the inner membrane, the middle membrane and the outer membrane of the blood vessel for deep administration, so that the medicine utilization rate is improved. After the medicine is released, the outer tube is continuously pushed to the proximal end of the support 1, the support 1 is retracted to be folded into the outer tube 4 for recycling, and the outer tube 4 is driven to move out the support 1 together. The medicine covered stent can not remain in blood vessels, and meanwhile, the mode can not block blood flow, can prolong the administration time, and has simple and convenient whole operation process and easy operation.
In addition, in order to further facilitate the operation, fig. 16 is a schematic view of the drug carrying system in a blood vessel, and the recoverable drug carrying system is further provided with a Y valve 7, as shown in fig. 16, the Y valve fixedly connects the outer tube, the tearable sheath, the drug covered stent and the rear expanding balloon, so that the relative sliding among the instruments can be reduced, and the accurate positioning can be realized. The tearable sheath 4 is sleeved on the drug covered stent 1, the drug covered stent 1 is sleeved on the rear expanding balloon 2, a balloon guide wire cavity can be communicated with a guide wire 8, the Y valve 7 can adjust the size of an inner hole of the Y valve through an adjusting nut, and the recyclable covered drug covered stent and the rear expanding balloon penetrate through the inner hole of the Y valve 7 to fix the push rod 5 part of the drug covered stent. The Y valve 7 can adjust the size of an inner hole of the Y valve through an adjusting nut, the recyclable tectorial membrane drug stent 1 and the post-expansion balloon 2 penetrate through the inner hole of the Y valve, the push rod part of the recyclable tectorial membrane drug stent is fixed, the far-end development 104 of the stent does not exceed the far-end development 201 of the post-expansion balloon, and the far-end development 401 of the outer tube does not exceed the far-end development 201 of the post-expansion balloon.
At this time, the guide wire 8, the rear expanding balloon 6, the drug covered stent 1, the tearable sheath 3, the outer tube 4 and the Y valve 7 are sleeved in sequence from inside to outside. The stent 1 is pre-assembled in the tearable sheath 3 after being compressed, the stent 1 is sleeved on the rear expanding balloon 2, the tearable sheath 9, the stent 1 and the rear expanding balloon 6 are sleeved in the outer tube 4, the tearable sheath is sleeved on the recyclable film coated drug stent, the recyclable film coated drug stent is sleeved on the rear expanding balloon, the balloon guide wire cavity can be communicated with the guide wire 8, the Y valve 10 can adjust the size of the inner hole of the Y valve through an adjusting nut, and the recyclable film coated drug stent and the rear expanding balloon penetrate through the inner hole of the Y valve to fix the push rod part of the recyclable film coated drug stent. Before operation, the rear expanding saccule far-end developing ring 201 is flush with the position of the support far-end developing spring 104, the rear expanding saccule 2 is preloaded in the inner cavity of the support 1, the support 1 is compressed in the tearable sheath 3 in a folded state, the support far-end developing ring 104 is flush with the far end of the tearable sheath, the support far-end developing ring and the rear expanding saccule far-end developing ring are positioned in the same position and preloaded in the tearable sheath, the outer tube is sheathed on the tearable sheath, and the Y valve penetrates through the inner hole of the Y valve 7 to fix the push rod 5 part of the recyclable tectorial medicine support and the rear expanding saccule. During operation, the guide wire 8 is released to the target blood vessel position, the rear expanding balloon can be used for passing through the guide wire, the recyclable drug carrying system is conveyed to the target blood vessel position along the guide wire position, the Y valve 7 is loosened, the outer tube 4 is withdrawn later, the tearable sheath 3 is placed in the blood vessel, the indentation line of the flexible part of the tearable sheath 3 is torn from the middle part under the expansion action of the rear expanding balloon through the expansion force of the balloon 2 and the radial expanding force of the bracket, and then the tearing area is gradually spread to the proximal end part and the distal end part until the indentation line is fully opened. The stent is in an expanded state and is adhered to a blood vessel, the tearable sheath is retracted after the stent is released, and the subsequent operation is consistent with the operation.
In this embodiment, the guidewire 8 remains in the central lumen of the system to ensure operational safety. The invention adopts an expanding saccule or a short micro-catheter which is preset in the covered stent as a loader to form a rapid exchange system along the guide wire. The system ensures normal forward blood flow during operation, prolongs the attaching time of the coated stent coated with the medicine at the lesion position, and improves the medicine absorption rate. The balloon, the stent or the intra-cavity image catheter can be accessed at any time after the covered stent is released. The method is convenient for carrying out intracavity image examination on the adherence degree of the covered stent or simultaneously treating the lesions at the far end of the covered stent. The balloon-assisted stent graft drug delivery system can better adhere to the vessel wall. Fig. 17 is an intravascular image of the drug delivery system. As shown in fig. 17, long-term vessel wall abutment promotes drug release and absorption, reducing elastic recoil of lesion parts. Because the diameter of the stent is limited, the formation of blood vessel interlayers and hematomas caused by the excessive expansion of the saccule can be avoided, the formed interlayers and hematomas can be improved, and the complications can be reduced. The drug loading rate is obviously increased after the surface of the stent is coated, so that the intimal hyperplasia is effectively inhibited, the restenosis rate is effectively reduced, and the treatment effect is improved. The stent coating strengthens the integral structure of the self-expanding stent and is beneficial to positioning, releasing and recycling of the stent. More importantly, the device is placed in the blood vessel in a non-mechanical way.
Animal experiment:
The drug delivery system prepared in example 1 was subjected to pharmacokinetic studies using a common animal model of common Bama pig iliac arteries. And establishing correlation between animal experiments and clinical application of the drug-coated stent application by over-expanding animal healthy blood vessels (the expansion ratio is 1.1-1.3:1). The recoverable drug carrying system is sprayed with drug carrying quantity to 3 mug/mm 2, and animal experiments are carried out after packaging and sterilization. The drug-coated stent is respectively expanded for 1min, 5min, 10min and 15min at the left rear leg iliac branch and the right rear leg iliac branch of the Bama pig and then retracted, and angiography is shown in the figure. Each time point was sacrificed and dissected from the bar Ma Zhu immediately after the end of the procedure and the dilated vessels were removed for examination. The data obtained for the drug content in the tissue is shown in fig. 18.
The recoverable drug carrying system has the intravascular tissue drug contents of 0mg/g, 6.74mg/g, 12.58mg/g and 13.04mg/g after the left iliac artery is respectively expanded for 1min, 5min, 10min and 15min, the intravascular tissue drug contents of 0mg/g, 5.81mg/g, 6.30mg/g and 36.43mg/g after the left iliac artery is respectively expanded for 1min, 5min, 10min and 15min, and the average value of 0mg/g, 6.28mg/g, 9.44mg/g and 24.74mg/g after the same common iliac artery is respectively expanded for Ma Zhu min, 5min, 10min and 15 min.
The experimental results show that the content of the obtained tissue has a remarkable rising trend along with the increase of the time for placing the drug-coated stent of the recoverable drug-carrying system in the blood vessel.
It is finally necessary that the above embodiments are only for further detailed description of the technical solutions of the present application and should not be construed as limiting the scope of the present application, and any person skilled in the art should make some changes, modifications, substitutions, combinations and simplifications by using the technical contents disclosed above without departing from the scope of the technical solutions of the present application, all of which are included in the scope of the present application.