WO2011100869A1

WO2011100869A1 - Biocompatible stent with sliding clips

Info

Publication number: WO2011100869A1
Application number: PCT/CN2010/070701
Authority: WO
Inventors: 孙锟; 孙康; 冯其茂; 姜闻博; 窦红静; 李伟
Original assignee: 上海交通大学医学院附属新华医院
Priority date: 2010-02-22
Filing date: 2010-02-22
Publication date: 2011-08-25

Abstract

A biocompatible stent with sliding clips includes: a stent body with mesh structure; the stent head, which is located at one end of the stent body and is integrated with said stent body, and which provides a sliding-clip effect when the stent is being curled; stent clips, which are integrated with the stent body and fix the tubular structure of the stent when it is being curled.

Description

Biological scaffold with slider

Field of the Invention This invention relates generally to the field of medical devices, and more particularly to a novel slider bioresorbable stent for use in dilating blood vessels, as well as in stenotic sites of organs such as the trachea, esophagus, urethra, and biliary tract. Background technique

Congenital heart disease is the most common cardiovascular disease in childhood, with an incidence rate of 0.678% of live births. Congenital heart disease in infants with congenital pulmonary and pulmonary venous stenosis, venous and aortic and branch stenosis 7% to 15% of all congenital heart disease, and the right ventricle-pulmonary artery artificial conduit (RV-PA tubing) stenosis, restenosis after pulmonary artery and pulmonary vein surgery, and the re-stenosis of the body vein and aorta and their branches The number of patients with stenosis and stenosis of the Fontan channel will continue to increase as the ability to treat congenital heart disease increases. However, in clinical practice, the treatments commonly used in infants and young children, such as percutaneous balloon dilatation or thoracotomy, are extremely difficult. Surgical treatment of congenital heart disease often associated with right ventricular outflow tract and pulmonary artery stenosis in infants and young children is difficult to reconstruct small pulmonary arteries, prone to postoperative residual obstruction and lead to recent reoperation, and 5 years of The rate of restenosis can be as high as 50-60%. Percutaneous transluminal balloon dilatation can have a certain effect, but the rate of restenosis can still be as high as 40%, and the effect of stenosis and restenosis due to vascular torsion or compression due to external forces is often unsatisfactory. Recent studies have shown that stenting is an ideal treatment for this type of lesion.

Currently used vascular stents are all woven from metal. After the stent is implanted, it supports the vascular wall at an early stage to prevent retraction. With the endothelialization of the stent and the reconstruction of the vessel wall in the later stage, the stent only needs temporary support. However, the size of the metal stent after implantation is not changed with the growth of the blood vessel, and it is likely to cause artificial stenosis due to mismatch with the size of the blood vessel. Metal stents also have the following defects: (1) long-term antiplatelet therapy is easy to form thrombus; (2) lifelong retention in the human body, affecting subsequent possible surgical treatment; (3) appearing in nuclear magnetic resonance and CT examination Artifacts. Therefore, bioresorbable stents are bound to be the most promising.

For the materials used in bioabsorbable stents, the current research is mainly poly-L-lactic acid, but also polyoxycyclohexanone and polycaprolactone. These materials gradually degrade in the body, participate in metabolism in the body and are excreted; It has been approved for FDA approval and can be implanted in the body. The Igaki-Tamai stent is designed for bioabsorbable stents: Zig-Zag shape design; REVA stent: The entire stent has a slide & lock design; Four-leaf structural bracket: It is based on four leaves made of fiber The structure, the coil continues to surround the entire body of the stent, and when the stent is fully expanded, it has a spiral coil plus three longitudinal fibers. The common feature of these brackets is that they are all complete cylindrical types before expansion, but all have problems, that is, the support force of all the brackets is insufficient, and the elastic contraction of the brackets is easy to occur. Summary of the invention

The object of the present invention is to solve the bottleneck of the interventional treatment method for vascular stenosis in infants and young children, and the problem of insufficient support force of the bioabsorbable stent; and to provide a novel bioabsorbable stent, which not only has the support of improving the support of the stent but also has completely different new types. The shape of the slider design.

The invention provides a novel slider bioresorbable stent, which is a sheet shape before implantation, comprises a stent body with a mesh structure, a stent head which acts as a sliding buckle at one end of the stent body and during the curling process of the stent The bracket body is fixed into a tubular bracket buckle. According to the position of the bracket buckle, it is divided into three types: buckle type, edge slide type and intermediate slide type.

As shown in Figure 1, a bioabsorbable slider bracket in accordance with one embodiment of the present invention is shown. The bracket includes: a flat bracket body, a bracket head at one end of the body, and a bracket buckle. A row of mesh holes is arranged on the body portion of the bracket, and the sizes of the mesh holes may be the same or different. In one embodiment of the invention, each mesh size is evenly distributed, e.g., the mesh size is 0.5-3 mm. The mesh can be of any shape, including circles, ovals, squares, rectangles, triangles, polygons, and the like. In one embodiment of the invention, the mesh is circular. The bracket buckle is located near the head of the bracket, as shown in Fig. 1, and includes 2-4 protruding buckles, which together with the outer frame constitute the slider device of the present invention. There may also be a plurality of raised buckles depending primarily on the size of the desired stent and the desired application. The length of the raised buckle is 0.5-lmm, at an angle relative to the plane of the stent, typically 20-40 degrees. However, those skilled in the art will understand that it can be any other angle. The size of the outer frame is adapted to the size of the body of the bracket, so that during the crimping process of the bracket, the inner protruding buckle can be strictly slid along the length of the sheet to avoid misalignment. The tabs of the protrusions can be arbitrarily inserted into any of the rows of meshes during sliding, so that the sheets can be fixed into a tubular shape.

As shown in Fig. 2, a bioabsorbable slider bracket according to another embodiment of the present invention is shown. The bracket The utility model comprises a flat bracket body, a bracket head at one end of the body and a bracket buckle. The bracket includes a longitudinal axis Z extending parallel to the head of the bracket and a transverse axis X extending perpendicular to the head of the bracket, as shown. A row of mesh holes is arranged on the body portion of the bracket, and the sizes of the mesh holes may be the same or different. In one embodiment of the invention, each mesh size is evenly distributed, for example, the mesh size is 0.5-3 mm. The mesh can be of any shape, including circles, ovals, squares, rectangles, triangles, polygons, and the like. In one embodiment of the invention, the mesh is circular. The bracket head includes an outer frame that is sized to fit the body of the bracket. In the embodiment shown in the figures, the bracket buckle is embodied as teeth on both sides of the bracket body, the bracket body can pass through the outer frame during the curling of the bracket, and the tooth structures on both sides can follow the outer frame Both edges slide. During the sliding process, the teeth engage the outer frame to enable the sheet to be fixed into a tubular shape. In one embodiment, the teeth have a size of 0.1 mm. All of the teeth extend away from the head of the stent at an angle relative to the transverse axis of the stent, for example 30-60 degrees. In one embodiment of the invention, the teeth are at an angle of 30 degrees with respect to the transverse axis of the stent.

As shown in Fig. 3, a bioabsorbable slider bracket according to still another embodiment of the present invention is shown. The bracket includes a flat bracket body, a bracket head at one end of the body, and a bracket buckle. As shown, the bracket includes a longitudinal axis Z that extends parallel to the head of the bracket and a transverse axis X that extends perpendicular to the head of the bracket. A row of mesh holes is arranged on the body portion of the bracket, and the sizes of the mesh holes may be the same or different. In one embodiment of the invention, each mesh size is evenly distributed, for example, the mesh size is 0.5-3 mm. The mesh can be of any shape, including circles, ovals, squares, rectangles, triangles, polygons, and the like. In one embodiment of the invention, the mesh is circular. The bracket head includes a buckle structure between the outer frame and the outer frame, and both ends of the buckle are connected with the outer frame. In one embodiment, the buckle structure has a length of 0.5-lmm. The body of the stent includes teeth corresponding to the buckle structure, the teeth extending away from the head of the stent. In one embodiment, the teeth have a size of 0.1 mm. The teeth are at an angle relative to the transverse axis of the stent, for example at an angle of 30-60 degrees. In one embodiment of the invention, the teeth are at an angle of 30 degrees with respect to the transverse axis of the stent. During the curling process of the bracket, the tooth structure slides along both sides of the buckle structure in the outer frame of the bracket head, and during the sliding process, the tooth buckles the buckle structure of the outer frame, so that the sheet can be fixed Tubular. In the embodiment shown in Figures 2 and 3, since all the teeth are oriented in the same direction, the bracket cannot be retracted after being fastened. During delivery to the body, the stent is tightly rolled up and attached to the balloon of the delivery device. After reaching the designated site, the balloon expands to expand the diameter of the stent and suck back the balloon. As the pressure bracket of the blood vessel wall is immediately buckled, it supports the blood vessel wall.

Materials for bioabsorbable stents include polylactic acid (PLA;), polydioxanone (PDO), polycaprolactone (PCL;), polyglycolic acid (; PGA;), polyhydroxybutyric acid ( ; PHB) and other high-molecular polymers and new polymers produced by copolymerization, blending, modification, etc. of different polymers. After being implanted into the human body and completing mechanical support, the degradable material can be degraded into small molecules that are safe and harmless to the human body and excreted. The fabrication of the stent includes molding, machine printing, laser engraving, and the like.

Unlike the currently bioabsorbable vascular stents, the unique slider design is unique. Before the expansion, other bioabsorbable stents are cylindrical, and the sliding-button bioabsorbable blood vessels are a sheet-like structure; after the stent is expanded, there is almost no elastic retraction, which significantly increases the radial support force of the stent.

Unlike conventional metal vascular stents, the bioabsorbable vascular stents of the present invention have a completely new concept. Firstly, before the expansion, the metal stents are all cylindrical, and the sliding-button bioabsorbable blood vessels are in a piece-like structure; the metal stents have different degrees of elastic retraction after expansion, and the stent has strong radial support force and almost no elasticity. Retracted. At present, the clinical metal stent is not a solution material, and the defects are:

(1) It is easy to reach thrombosis and requires long-term antiplatelet therapy; (2) Stay in the human body for life, affecting the possible subsequent surgical treatment; (3) Artifacts appear during MRI and CT examination. Since the bioabsorbable stent is an absorbable material, the above problems are not present, and can be applied not only to stenotic lesions such as coronary artery, renal artery, abdominal aorta, thoracic aorta, and carotid artery in adults, but also to solve vascular stenosis in infants and young children. Interventional therapy for a particular type of disease. It can also be used for the treatment of stenosis in organs such as the trachea, esophagus, urethra, and biliary tract in adults and children. DRAWINGS

1 is a schematic view of a slider bracket according to an embodiment of the present invention.

2 is a schematic view of a slider bracket according to an embodiment of the present invention.

3 is a schematic view of a slider bracket according to an embodiment of the present invention.

4 is a photographic view of the slider holder of the present invention before implantation.

Figure 5 is a photographic view of the slider holder of the present invention after implantation. Specific example

Example 1: The in vitro simulated release of a polycaprolactone (PCL) snap-type stent was observed. First, materials and methods:

Materials: Polycaprolactone (PCL) snap-on brackets 20*8mm each, 6cm diameter rubber hose, bracket delivery system and pressure pump.

Method:

1. First use a pressure pump to suck the balloon of the delivery system into a negative pressure, then withdraw the outer sheath tube, crimp the buckle bracket onto the delivery system balloon, and push the outer sheath tube forward to the cone to wrap. support.

2. Insert the stent delivery system along the guide wire into the target site of the artificial blood vessel, and expand the stent at 12atm*30 seconds.

3, suck back the balloon into a negative pressure, and then withdraw the balloon.

Second, the observation indicators:

1. Vessel lumen diameter: After the balloon is removed, the diameter of the vessel lumen at the stent is measured.

2. Acute elastic retraction rate:

Acute elastic retraction rate of the stent = (diameter when the stent is fully expanded - stent diameter after balloon removal y diameter when the stent is fully expanded).

3. Successful deduction rate:

Evaluation criteria: Success: After the balloon is removed, the stent buckle is stuck; Failure: After the balloon is removed, the stent is not buckled and slides into the lumen.

Third, the results:

PCL-type stents can be released under normal release pressure (10-14 atm), the stent can be successfully buckled, no stent curls into the lumen; the stent basically maintains a preset lumen diameter, with extremely low Acute elastic retraction rate (0.4%). Prove that this bracket design operation is feasible.

Table 1: Results of PCL Snap-on Brackets

Example 2: Observation of in vitro simulated release of polycaprolactone (PCL) edge slide-type stent I. Materials and methods:

Materials: Polycaprolactone (PCL) edge slide-type brackets 20*8mm each, 10 cm diameter rubber hoses, bracket delivery system and pressure pump. method:

1. First use a pressure pump to draw the balloon of the delivery system into a negative pressure, then withdraw the outer sheath tube, crimp the stent onto the delivery system balloon, and push the outer sheath tube forward to the cone to wrap the stent.

Second, the observation indicators:

2. Acute elastic retraction rate:

3. Successful deduction rate:

Third, the results:

PCL edge slide-type brackets can be released under normal release pressure (l l-15atm), the stent can be successfully buckled, no stent curls into the lumen; the stent basically maintains a preset lumen diameter, which is extremely low The acute elastic retraction rate (0.35 %). Prove that this bracket design operation is feasible.

Table 2: Results of the PCL edge slider type bracket

Example 3: Observation of in vitro simulated release of polycaprolactone (PCL) intermediate slide-type stent I. Materials and methods:

Materials: Polycaprolactone (PCL) intermediate slide-type brackets 20*8mm each, 10cm diameter rubber hoses, bracket delivery system and pressure pump.

Method:

1. First use a pressure pump to suck the balloon of the delivery system into a negative pressure, then withdraw the outer sheath tube, and slide the buckle bracket The crimp is wound around the delivery system balloon and the outer sheath is pushed forward to the cone to wrap the stent.

Second, the observation indicators:

2. Acute elastic retraction rate:

3. Successful deduction rate:

Third, the results:

PCL intermediate slide-type brackets can be released under normal release pressure (1 1-15 atm), the stent can be successfully buckled, no stent curls into the lumen; the stent basically maintains a preset lumen diameter, with a pole Low acute elastic retraction rate (0.34%). Prove that this bracket design operation is feasible.

Table 3: Results of the PCL intermediate slide-type bracket

Example 4: Observation of in vitro simulated release of poly(p-dioxanone) (PDO) buckle-type scaffolds I. Materials and methods:

Materials: Polydioxanone (PDO) with snap-on brackets 20*8mm each, 10cm diameter rubber hose, bracket delivery system and pressure pump.

Method:

2. Insert the stent delivery system along the guide wire into the target site of the artificial blood vessel, 12atm*30 seconds expansion Release the stand.

Second, the observation indicators:

2. Acute elastic retraction rate:

3. Successful deduction rate:

Third, the results:

PDO buckle-type stents can be released under normal release pressure (10-14atm), the stent can be successfully buckled, no stent curls into the lumen; the stent basically maintains a preset lumen diameter, with very low acute Elastic retraction rate (0.5%). Prove that this bracket design operation is feasible.

Example 5: Observation of in vitro simulated release of poly(p-dioxanone) (PDO) edge slider-type stent

First, materials and methods:

Materials: Polydioxanone (PDO) edge slide-type bracket 20*8mm each, 6cm diameter rubber hose, bracket delivery system and pressure pump.

Method:

2. Insert the stent delivery system along the guide wire into the target site of the artificial blood vessel, and expand the stent at 12atm*30 seconds. 3, suck back the balloon into a negative pressure, and then withdraw the balloon.

Second, the observation indicators:

2. Acute elastic retraction rate:

3. Successful deduction rate:

Third, the results:

The PDO edge slider type bracket can be released under normal release pressure (10-14atm), the bracket can be successfully buckled, no bracket curls into the lumen; the stent basically maintains the preset lumen diameter, which has extremely low Acute elastic retraction rate (0.3%). Prove that this bracket design operation is feasible.

Example 6: Observation of in vitro simulated release of poly(p-dioxanone) (PDO) intermediate slide-type stent

First, materials and methods:

Materials: Polydioxanone (PDO) intermediate slide type bracket 20*8mm each, 10cm diameter rubber hose, bracket delivery system and pressure pump.

Method:

3, suck back the balloon into a negative pressure, and then withdraw the balloon. Second, the observation indicators:

2. Acute elastic retraction rate: Acute elastic retraction rate of the stent = (; diameter when the stent is fully expanded - stent diameter after balloon removal y diameter when the stent is fully expanded.

3. Successful deduction rate:

Third, the results:

PDO intermediate slide-type brackets can be released under normal release pressure (10-16atm), the brackets can be successfully buckled, no brackets curl into the lumen; the stent basically maintains a preset lumen diameter, with extremely low Acute elastic retraction rate (0.43 %). Prove that this bracket design operation is feasible.

Table 6: Results of the PDO intermediate slide-type bracket

Example 7

The porcine iliac artery was stented with a polydioxanone (PDO) edge slide-type stent to observe its efficacy.

I. Materials and methods

Materials: 25Kg pigs 15 heads, sputum needles, guidewires, 9F sheaths, panex, chloramphenicol, heparin, stent delivery systems, pressure pumps and GE-2005 angiographs.

Sample content: 15 pigs, PDO slider bracket 20*6mm20.

Specific steps:

1. Chloramphenicol 10mg/Kg The pig is anesthetized, tracheal intubation, ECG monitoring, routine disinfection without bacteria towel, through the left carotid artery, and placed into the 9F sheath.

2. Perform left and right radial angiography and select implanted blood vessels. The diameter of the stent is required to be 25% larger than the diameter of the blood vessel. 3. Using a pressure pump to suck the balloon of the delivery system into a negative pressure, withdraw the outer sheath tube, crimp the buckle bracket onto the delivery system balloon, and push the outer sheath tube forward to the cone to wrap the bracket. . The stent delivery system was inserted along the guidewire into the target site, and the 12-15 atm*30 second expanded release stent. Intraoperative heparin 100U/Kg.

4, suck back the balloon into a negative pressure, withdraw the balloon, and perform angiography again.

Second, the observation indicators:

1. Acute elastic retraction rate: (The diameter of the stent when the balloon is fully expanded - the diameter of the postoperative angiographic stent y. The diameter of the stent when the balloon is fully expanded.

2. Successful delivery rate of the delivery system: success: the stent is delivered to the target site, the stent is not detached, the stent is accurately positioned, and the stent is fully expanded.

3, the incidence of complications: including vascular tears, major bleeding, stent displacement, death.

4. The diameter of the blood vessel after implantation. After angiography, it was measured by computer.

Third, the results:

1. Stent implantation: See Table 7

Table 7: PDO slider bracket implant material characteristics

Acute elastic retraction rate 0.37±0.12

Complication rate 1 (5)

Delivery system success rate 20 (100)

Vessel diameter (mm) 5.92±0.06 It can be seen from the table that the PDO stent has almost no elastic retraction and shows strong support force; the new delivery system can successfully deliver the stent; there is a case of vascular rupture, contrast agent leakage, but The overall complication is low and the stent and delivery system are designed to work.

3. Contrast images before and after stent implantation:

Figure 4 is a contrast image of the porcine artery before stent implantation to determine the site of stent implantation. Figure 5 is a contrast image after stent implantation. As shown in the figure, the vessel wall is expanded by the stent and the stent vessel is unobstructed. The patents, patent applications, publications and documents referred to herein are not an admission that any of the above-mentioned documents are prior art or the contents or dates of those publications or documents.

Improvements may be made to the above without departing from the fundamental aspects of the invention. Although the present invention has been described with reference to one or more specific embodiments, it will be apparent to those skilled in the art that Conception. The invention illustratively described herein can be implemented in the absence of one or more elements specifically disclosed herein. Thus, for example, in the examples of the present invention, any of the terms "comprising", "consisting essentially of" and "consisting of" may be in two other terms. Any of the alternatives. Therefore, the terms and expressions used are for the purpose of description and not of limitation, and the claims

Claims

Rights request

An implantable lamella-shaped integrated slider biological scaffold comprising:

a flat stent body, the stent body having a mesh structure;

a bracket head located at one end of the bracket body, the bracket head being integrally formed with the bracket body, the size of which is adapted to the bracket body, and the bracket head functions as a sliding buckle during the curling process of the bracket; with

A bracket buckle is also integrally formed with the bracket body for fixing the bracket into a tubular bracket buckle during the curling of the bracket.

2. The slider bio-bracket according to claim 1, wherein the bracket head is in the form of an outer frame, the size of which is adapted to the body, and the bracket buckle is a protrusion near the head of the bracket. In the form, the outer frame allows the bracket body to pass therethrough during the curling of the bracket, thereby sliding the protrusion along the bracket body and inserting into the mesh to fix the sheet into a tubular shape.

3. The slider bio-bracket according to claim 2, wherein the bracket buckle in the form of a protrusion near the head of the bracket is angled with respect to a plane of the bracket body.

4. The slider bio-bracket according to claim 2, wherein the mesh is evenly distributed.

The slider bio-bracket according to claim 1, wherein the bracket head is in the form of an outer frame, and the size thereof is adapted to the bracket body, and the bracket buckle is a tooth located on two sides of the bracket body. The outer frame allows the bracket body to pass therethrough during the curling of the bracket, and the teeth on both sides of the body slide along both edges of the outer frame, and during the sliding process, the buckle body is locked The outer frame is described, and the sheet is fixed into a tubular shape.

6. The slider bio-bracket of claim 5, wherein the teeth extend away from the head of the bracket and are angled relative to a transverse axis of the bracket body.

The buckle bio-bracket according to claim 1 , wherein the bracket head comprises an outer frame and a buckle connected to the outer frame of the outer frame, wherein the bracket buckle is represented by two sides of the bracket body a tooth corresponding to the buckle of the outer frame and the outer frame, the tooth structure sliding along the buckle structure of the outer frame and the outer frame of the bracket head during the curling process of the bracket, sliding In the process, the teeth are fastened to the buckle structure of the outer frame, so that the sheet can be fixed into a tubular shape.

8. The slider biorack of claim 7, wherein the teeth extend away from the head of the bracket and are angled relative to a transverse axis of the bracket body.

9. The slider bio-bracket according to claim 1, wherein the material of the stent comprises: polylactic acid (PLA;), polydioxanone (PDO), polycaprolactone (PCL) ;), high molecular weight polymers such as polyglycolic acid (PGA), polyhydroxybutyric acid (PHB), and new polymers produced by copolymerization, blending, modification, etc. of different polymers.