WO2018036434A1 - Implant-type, completely bioabsorbable, vascular polymer stent - Google Patents

Abstract

Disclosed is an implant-type, completely bioabsorbable, vascular polymer stent comprising five or more annular corrugated support struts (1), and connecting struts (2) spaced apart and connected between the support struts (1). The support struts (1) are formed by corrugations resembling an "Ω" shape (3) and corrugations resembling an "m" shape (4) being alternately connected with each other, wherein the corrugations resembling an "Ω" shape (3) and the corrugations resembling an "m" shape (4) are respectively composed of two sets of upright "s" parts and inverted "s" parts connected together, and the connection between two adjacent support struts (1) is formed by means of the connecting struts (2) connecting the top of the corrugations resembling an "Ω" shape (3) and the bottom of the corrugations resembling an "m" shape (4). The stent balances radial supporting force, wall thickness and flexibility, has good passing-through performance, can also provide sufficient mechanical support at a lesion segment for a specified period of time for wound healing, and is be gradually absorbed by the body after the wound heals, with good endothelialisation, thereby effectively reducing the stent restenosis rate and the risk of late stent thrombosis.

Description

Implantable fully bioabsorbable vascular polymer scaffold Technical field

The invention belongs to the field of medical instruments, and in particular relates to an implantable fully bioabsorbable vascular polymer stent.

Background technique

Since the first metal stent, Palmaz-Schatz, has been implanted into the human body in 1985, stent intervention has successfully solved the problem of high restenosis rate in the simple balloon expansion era, and has become the main means of clinical treatment, with more and more After the metal stent was implanted into the human body, it was found that the rate of restenosis in the stent was still as high as about 20% due to inflammatory reaction, neointimal hyperplasia, negative vessel remodeling, and delayed stent endothelialization.

In order to solve this problem, the first generation of polymer-coated drug-eluting stents came into being. The emergence of drug-eluting stents will reduce restenosis after interventional therapy from 30-40% in the PTCA era, 15-25% in the BMS era, to less than 10% now, and even the emergence of drug-eluting stents It is one of the milestones of coronary interventional therapy and has epoch-making significance.

However, analysis and research published at the ESC/WCC meeting in Barcelona in September 2006 showed that the non-degradable polymer drug-eluting stent has permanent stimulation and local inflammation on the vessel wall due to long-term residual drug-loaded polymer coating on the stent surface. Reaction, etc., resulting in increased risk of thrombosis in the late stent, hyperplasia of the intima, and the like.

Studies have shown that the occurrence of late stent thrombosis is closely related to the delay of endothelialization after stenting. Endothelialization means that after the stent is implanted into the blood vessel, the stent rod is embedded in the vessel wall to form a groove, and some endothelial cells remain in the unembedded portion. These endothelial cells gradually multi-center growth, fuse with each other, and finally cover the entire inner wall of the branch. Completed in a few weeks. The degree of endothelialization is an important indicator of histological prediction of the probability of late stent thrombosis.

The long-term residual of the permanent drug stent in the blood vessels causes chronic damage of the blood vessels, which will cause atrophy of the middle layer of the blood vessels, formation of aneurysms, and reactive intimal hyperplasia, which eventually leads to the occurrence of vascular restenosis. In clinical practice, only the stent plays a role in mechanical support of the vessel during the specific time of injury healing. Therefore, the best vascular polymer stent should be adequately supported by the lesion segment and gradually absorbed by the body after healing.

At present, there are a lot of biodegradable polymer vascular stents, in order to temporarily support the blood vessel wall, keep the blood vessels unblocked, and gradually be absorbed by the body in the later stage.

However, the commonly used high molecular polymer materials generally exist: insufficient mechanical strength results in poor radial compressive strength of the stent, the bristle is easily broken, and the material has mechanical relaxation behavior, resulting in unstable stent performance and radial support force decreasing with time. Shelf life Short life and other issues. In order to improve the mechanical properties of polylactic acid, many domestic and foreign counterparts have studied polylactic acid vascular polymer stents. Venkatraman et al. improved the process to make the support strength of PLLA stents reach 0.21~0.25MPa, while ordinary stainless steel stents The support strength is 0.20~0.22MPa. In terms of mechanical strength, PLLA can reach the level of metal bracket. The applicant's previous research results apply for patent CN102499999B, and the polylactic acid pipe used for preparing the polymer support is modified, and the support strength is further satisfied when used for the support.

In addition, the stents that are marketed or under development have a variety of tread pattern structures, wherein the m (or w) shape and the n (or Ω) shape are considered to be better embodiments in the study, the main purpose of which is to enable the stent to be radially compressed and Radial expansion and still maintain adequate support to reduce acute rebound and reduce the incidence of stent restenosis. For example, US Pat. No. 5,514,154 A first proposed an m- or w-shaped and n (or Ω)-shaped structural pattern holder.

However, there are obvious deficiencies in the radial support force and flexibility. In the follow-up study, in order to solve the existing problems, the researcher carries out transformation and optimization. For example, the applicant's previous research program CN201431532Y provides a crown. a pulse bracket, the bracket includes five or more annular wave-shaped support rods, and a connecting rod spacedly connected between the support rods, wherein the support rods at both ends of the bracket are "Ω"-shaped waves, both ends A connecting rod between the supporting rod and its adjacent supporting rod is connected between two adjacent "Ω" shaped wave tops; the supporting rod of the middle portion of the bracket is alternately connected by "m" and "Ω" shaped waves The connecting rod between the distal second row of support rods and the third row of support rods is connected between two adjacent "m" shaped wave bottoms, and the connecting rods between the remaining part of the supporting rods are connected adjacent to each other" Between the m" wave bottom and the "Ω" wave top. This solution is more suitable for the application of metal brackets, and its support force and flexibility are more constrained when used in the polymer stent scheme.

In addition, CN1923154A provides an expanded vascular stent for percutaneous angioplasty for the treatment of vascular occlusion. In addition to being used for cardiovascular, the structural stent is also suitable for peripheral blood vessels. The thin-walled microtubes are laser-engraved into a mesh structure, and the structure is formed by connecting a plurality of sets of wave support rings through connecting rods, and each group of wave support rings is composed of 2 - 5 sets of multiple unit wave combinations, connecting 2 to 10 connecting rods between adjacent wave support rings. The above structural design ensures that the tissue prolapse after the stent is implanted is small, the interference of the stent rod during the crimping and expansion is avoided, and the flexibility is increased. However, this solution also has a large disadvantage in terms of setting a smaller grip diameter, and particularly for a polymer stent, in terms of support and stability of its segments.

In addition, the existing wall thickness of the degradable stent is thicker than that of the metal stent by the material and processing means, which is twice or more than that of the metal stent, thus increasing the difficulty for the endothelial cells to climb the stent rod and completely wrap. It makes the surface of the stent difficult to re-endothelial, which affects the risk of thrombosis in the stent.

At present, various fully bioabsorbable stents on the market are not able to achieve perfect integration of various technical indicators, especially the radial support force, wall thickness and flexibility of the stent.

Summary of the invention

In view of the problems in the prior art, the present invention provides an implantable fully bioabsorbable vascular polymer stent that reconciles the contradiction between the radial support force of the fully bioabsorbable stent and the wall thickness and flexibility. Take care of both, to meet clinical needs.

The technical solution to solve the problem of the present invention is as follows:

An implantable fully bioabsorbable vascular polymer stent characterized by comprising more than five annular wave-shaped support rods and a connecting rod spacedly connected to the support rod bracket, the support rod of the bracket being of the class "Ω The shape wave and the "m" wave are alternately connected. The "Ω" wave and the class "m" are respectively composed of two sets of positive "s" and inverted "s", respectively. The connection between the rods is connected by a connecting rod at the "Ω"-shaped wave top and the "m"-shaped wave bottom, and the connecting rod is shaped like a straight rod.

Among them, the "Ω"-shaped wave and the "m"-like shape are respectively composed of two sets of positive "s" and inverted "s" connections, and if they are connected by a straight rod or a straight structure with a straight transition, whether it is a crest or The stress concentration of the connected straight rod is very obvious, and the bracket is easily fatigued and fractured. However, the core design of the present invention adopts two sets of positive "s" and inverted "s" connections, which can greatly reduce the stress concentration of the peak and the connecting rod position. It not only increases the support performance of the bracket, but also maintains the stability of the bracket performance.

One of the further preferred embodiments is that the angle between the positive "s" and the inverted "s" connecting segments is 5 to 45 degrees, preferably 10 to 30 degrees, and the support performance is enhanced as much as possible to improve stability. On the one hand, the specific design is based on the size of the outer diameter after the crimping. Through a large number of experiments, it is found that exceeding this range not only affects the outer diameter after the crimping, but also causes the support rod and the connecting rod to be squeezed. Pressing, so as to damage the film, affecting the release of the drug.

A further preferred embodiment is that the angle α1 of the aforementioned "Ω" shaped wave top ranges from 130 to 180 degrees; the angle α2 of the "Ω" shaped wave bottom ranges from 130 to 180 degrees.

The "Omega"-shaped wave top and the bottom of the wave adopt the above-mentioned range of angles, and the angle range of the arc-shaped transition section connected with the positive "s" or the inverted "s" is sufficiently large, so that the amplitude of the "Ω"-like wave is open or contracted. It is not very large. The amount of expansion required to provide support does not need to be large, and the extent of shrinkage is not large. It not only provides good support performance, but also maintains performance stability.

A further preferred embodiment is that the angle β1 of the aforementioned "m" shaped left (or right) wave top ranges from 90 to 130 degrees; the angle "β2" of the "m" shaped left (or right) wave bottom ranges from 130 to 180. degree.

The "m" shaped left (or right) wave top adopts the above range of angles, and the angular range of the curved transition section connected with the positive "s" or inverted "s" is sufficiently large that the "m" shaped wave is open or contracted. The amplitude is not very large, the amplitude that needs to be opened when providing support does not need to be large, and the degree of shrinkage is not large, which not only provides good support performance, but also maintains performance stability. The use of the above range of angles for the "m" shaped left (or right) wave bottom facilitates the control and connection of the angular extent of the straight rod to limit the force and width of the portion.

A further preferred solution is that the angle γ1 of the tangent of the "s" connection point and the tangent line of the "Ω"-shaped wave top is in the range of 5 to 30 degrees; the tangent of the "s" connection point and the "Ω"-shaped wave bottom The angle γ2 of the arc tangent is in the range of 5 to 30 degrees; the angle δ1 between the tangent of the "s" connecting point and the tangent of the "m" shaped wave top is 5 to 30 degrees; the "s" connecting point is tangent The angle δ2 with the tangent to the arc of the "m"-shaped wave bottom is in the range of 5 to 30 degrees.

The angle between the tangent of the "s" joint and the tangential line of the "Omega" or "m" shaped wave top (bottom) is the above range. The smoother the joint, the more uniform the force transmission and dispersion, and the formation of severe stress. Concentration affects stent performance and stability.

A further preferred embodiment is that the angle η1 of the "m" shaped wave bottom and the connecting rod ranges from 0 to 30 degrees; the angle η2 of the "Ω" shaped wave top and the connecting rod ranges from 0 to 30 degrees. .

The angle range of the "m" shaped wave bottom (or "Ω" shaped wave top) and the connecting rod is in the above range, which is advantageous for controlling the width of the connecting rod and controlling the outer diameter after the crimping; Increasing the angle of the "m" shaped wave bottom (like the "Ω" shaped wave top), which is based on the same angular range as the "m" shaped wave top. In this case, the smaller the stress concentration, the more effectively Reduce the severe stress concentration of the "m" shaped waves.

Furthermore, based on the preferred configuration of the foregoing structural design, it is further preferred that the ratio of the line connecting the "Ω"-shaped wave top and the wave bottom to the length of the connecting rod is in the range of 0.5 to 2, preferably 0.8 to 1.5; and the class "m" The ratio of the line connecting the wave top and the bottom of the wave to the length of the connecting rod ranges from 0.5 to 2, preferably from 0.8 to 1.5.

The connection between the "Ω"-like or "m"-shaped wave top and the bottom of the wave is too short with respect to the connecting rod, which is not only easy to cause the connecting rod and the "Ω"-shaped wave top and the "m"-shaped wave bottom. The stress concentration at the joint is obvious, and the stress concentration of the connecting rod is increased, and the flexibility is increased while the fatigue is excessively increased; the connection of the "Ω"-shaped wave wave top and the wave bottom is too long with respect to the connecting rod. When the grip is pressed, the support waveform is easily embedded in the support waveform of the adjacent ring, causing the support rod to be squeezed, thereby damaging the drug film and affecting the release of the drug.

It can be seen from the foregoing structural design that a synergistic effect is obtained in performance by adding a preferred ratio range of the length of the "Ω" shape and the "m" shape to the length of the connecting rod. Through the cooperation of the foregoing various solutions, the contradiction between the radial supporting force and the wall thickness and the flexibility is solved, and the three are considered. The relatively thin wall thickness of the bracket, under the good design of the bracket structure, still maintains sufficient radial support performance and excellent performance stability; at the same time, thanks to the relatively thin bracket wall thickness and good bracket The pattern structure, the outer diameter of the holder of the holder is small, the flexibility is good, the lesion can be smoothly reached, and the trauma of the implantation process and the damage of the stent are reduced.

Based on the foregoing aspects, it is further preferred that the widths of the support rods and the connecting rods are the same or different; and/or the widths of the support rods at both ends of the bracket are the same as or different from the widths of the support rods in the middle portion of the bracket; and/or The width of the connecting rod is the same as or different from the width of the connecting rod in the middle portion of the bracket.

By the same or different widths, the same solution is technically easier to implement and process, but to The need for foot support or strength, preferably in a different manner, in particular, preferably the thickness of one or both of the undulating support rods near the ends of the stent is greater than the width of the support rods near the intermediate portion. The width of the support rod and the connecting rod preferably ranges from 0.10 to 0.30 mm.

The focus of the present invention is on the design of the tread structure, the structure of which can be prepared by prior art or a suitably adjusted scheme. Usually, the mesh pattern of the bracket is laser engraved from the thin-walled pipe.

Through the foregoing scheme design, the present invention has found through extensive research that the prepared polymer stent has a radial strength of 240 kPa to 280 kPa in the case of controlling the inner diameter of 1.50 to 5.00 mm and the wall thickness of 0.05 to 0.2 mm. The support strength of the bracket.

Further preferably, the inner diameter is 2.50 to 4.00 mm, the wall thickness is 0.08 to 0.18 mm, and the radial strength is 250 kPa to 270 kPa. When the radial strength is satisfied, the maximum control wall thickness is sufficiently thin.

Further, the polymer stent has a load per unit axial length of 0.5-2.0 N/mm, preferably 1.0-2.0 N/mm, which satisfies the performance of various vascular lesion implants.

Unit axial length load refers to the load (pressure or pressure) of each unit axial length, that is, the total load/bracket length received by the bracket, expressed in N/mm.

It has been found by animal experimental research that the polymer stent provided by the invention can not only give sufficient mechanical support to the lesion segment within a certain time period of wound healing, but is gradually absorbed by the body after the wound is healed, and the endothelialization is good, and the stent is effectively reduced. Stenosis rate and risk of late stent thrombosis.

In the present invention, the material composition of the polymer scaffold is preferably one or two of the following polymers, or a mixture thereof, including: polylactic acid, L-polylactic acid, DL-polylactic acid, polyglycolic acid, polyhexyl Lactone and so on.

In order to meet the clinical use requirements of the stent, the stent surface (including the medial or lateral side) is coated with a coating that inhibits the vascular stenosis or inhibits implant rejection, and the coated carrier can be a variety of carriers with good biocompatibility.

The coated carrier material preferably comprises L-polylactic acid (PLLA), polylactic acid-glycolic acid copolymer (PLGA), racemic polylactic acid (PDLLA), polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate Alcohol ester, PVP, polyxylitol, polyglycerol ester, sodium alginate, chitosan, chitin, dextran, polyhard acid ester, polycitrate, etc.; the above coating carries a therapeutic dose of the drug Preferably, it comprises one or more of an antioxidant drug, an anticoagulant drug, an anticancer drug, a vascular smooth muscle cell hyperplasia drug, an anti-inflammatory drug or an immunosuppressive drug.

The above antioxidant drugs include superoxide dismutase, catalase, coenzyme Q10, glutathione peroxidase; anticoagulant drugs including aspirin, heparin, clopidogrel, etc.; anticancer drugs including colchicum Alkali, paclitaxel; inhibition of vascular smooth muscle cell proliferation drugs including vascular peptides, corticosteroids, calcium antagonists; anti-inflammatory drugs including dactinomycin, Depsidomycin, Kanglemycin C, Spergualin, Mytiocin, Gllooxin; immunosuppressive drugs including rapamycin , cyclosporine A, cyclosporine C, brefeldin A. The mass ratio of the above drug to the coated carrier is from 1:10 to 2:1, preferably from 1:3 to 1:1.

Advantageous effects of the present invention over the prior art include:

(1) The present invention provides an implantable fully bioabsorbable vascular polymer scaffold having an excellent tread design that maintains sufficient radial support performance over a relatively thin stent wall thickness, and The stability is excellent.

(2) The present invention provides an implantable fully bioabsorbable vascular polymer stent having a relatively thin stent wall thickness and a good stent pattern structure, the stent has a small outer diameter and a good flexibility. It has strong passing ability and operability, can successfully reach the lesion, reduce the trauma of the implantation process and the damage of the stent.

(3) The present invention provides an implantable fully bioabsorbable vascular polymer scaffold, which reconciles the contradiction between the radial support force of the fully bioabsorbable stent and the wall thickness and flexibility, and achieves a balance between the three and the clinical need.

(4) The present invention provides an implantable fully bioabsorbable vascular polymer scaffold coated with a coating for inhibiting blood vessel stenosis or inhibiting implant rejection by a stent surface (including an inner side or an outer side), a coating carrier It has good biocompatibility and meets the clinical needs of the stent.

(5) The preparation method of the stent of the invention is simple, easy to reproduce, and suitable for industrial production.

DRAWINGS

1 is a plan view showing a planar development of an implantable fully bioabsorbable vascular polymer stent, wherein the support rod 1, the connecting rod 2, an "Ω" shaped wave 3, and an "m" shaped wave 4.

2 is a schematic diagram in which a waveform is connected by a positive "s" and an inverted "s", in which a positioning arc reference line of an "Ω"-like wave or an "m"-like wave is used as a tangent L1 (or L1'), a circle The tangent L2 (or L2') of the arc of the arc and the "s" junction, L3 (or L3') is the tangent of the middle pole of "s", the angle of the positive "s" and the inverted "s" connection segment refers to The angle between L1 (or L1') and L2 (or L2'), the angle between L3 (or L3') and L2 (or L2') and the clamp of L1 (or L1') and L2 (or L2') The angles are basically the same, that is, the angles of the tangent arc entrance and the exit are substantially the same, which ensures the symmetry of the transition arc, thereby ensuring the uniformity of the force. Wherein, L1, L2 and L3, L1', L2' and L3' are each a group, and the angles correspond.

In Fig. 3, Figs. 3A-3G are schematic diagrams of an "m" shaped wave and an "Ω" shaped wave and a connecting rod, wherein the angle "α" of the "Ω" shaped wave top, the angle of the "Ω" shaped wave bottom 22; the angle "β" of the left (or right) wave top of the class "m"; the angle β2 of the left (or right) wave bottom of the "m" shape; the tangent of the "s" connecting point and the arc of the class "Ω" The angle γ1 of the tangent line, the angle γ2 between the tangent of the "s" joint and the tangent to the arc of the "Ω"-shaped wave; the angle δ1 between the tangent of the "s" joint and the tangent of the "m"-shaped wave top arc The angle δ2 between the tangent of the "s" connection point and the tangent of the "m"-shaped wave bottom; the angle between the "m"-shaped wave bottom and the connecting rod η1, the angle between the "Ω"-shaped wave top and the connecting rod Η2.

In Fig. 4, Fig. 4B is a partial enlarged view of the "Ω"-like wave of Fig. 4A, in which L4 is a line connecting the top of the "Ω"-shaped wave wave and the wave bottom.

In Fig. 5, Fig. 5B is a partial enlarged view of the "m"-shaped wave of Fig. 5A, wherein L5 is a line connecting the wave-like top and the wave bottom of the "m" shape.

6, FIG. 6A is a plan view showing the planar development of another implantable fully bioabsorbable vascular polymer stent according to the present invention. The end rod width of the stent is larger than the central rod width, and FIGS. 6B and 6D are enlarged views of the connecting rod of FIG. 6A. L6 is the length of the connecting rod, FIG. 6C is a partial enlarged view of the "Ω"-shaped wave of FIG. 6A, and FIG. 6E is a partial enlarged view of the "m"-shaped wave of FIG. 6A, and the "Ω"-shaped wave top and The length ratio of the connection between the wave bottom and the connecting rod is L4: L6, and the length ratio of the line connecting the "m" shaped wave top and the wave bottom to the connecting rod is L5: L6.

Figure 7 is a plan view showing the planar development of a further implantable fully bioabsorbable vascular polymer stent of the present invention.

Figure 8 is a SEM result of 30 days after implantation of the stent of the present invention.

Figure 9 is an OCT result immediately and 90 days after implantation of the stent of the present invention.

detailed description

The present invention will be further described in detail below with reference to the preferred embodiments and drawings, but the embodiments of the invention are not limited thereto.

Example 1 An implantable fully bioabsorbable vascular polymer scaffold

Referring to Figures 1, 2 and 3A-3G, an implantable fully bioabsorbable vascular polymer stent, comprising polylactic acid, comprising more than five annular wave-shaped support rods 1, and spaced apart from the support rod 1 a connecting rod 2 of the bracket, the support rod 1 of the bracket is alternately connected by an "Ω"-shaped wave 3 and an "m"-shaped wave 4, and the connection between two adjacent support rods is connected by the connecting rod 2 The "Ω" shaped wave top is connected to the "m" shaped wave bottom.

The "m" shaped wave 4, as shown in FIG. 3A, and the "Ω" shaped wave 3, as shown in FIG. 3B, are respectively composed of two sets of positive "s" and inverted "s" connections, respectively 2 is shown.

The shape of the connecting rod between the two adjacent support rods is a straight rod.

The implantable fully bioabsorbable vascular polymer scaffold is laser engraved from thin-walled tubing.

Example 2 An implantable fully bioabsorbable vascular polymer scaffold

Referring to Figures 1, 2 and 3A-3G, an implantable fully bioabsorbable vascular polymer stent comprises five or more annular waved support rods 1 and a connection spaced apart from the support rod 1 support. The rod 2 is different from the embodiment 1 in that the width of the support rod and the connecting rod are different in the specific embodiment, the width of the support rod at the two ends of the bracket is the thickest, and the connection between the two ends of the bracket is The width of the rod is second, and then the width of the remaining support rods, and the width of the remaining connecting rods is the thinnest. Among them, the angle of the positive "s" and inverted "s" connecting segments is 5-10 degrees.

Example 3 An implantable fully bioabsorbable vascular polymer scaffold

Referring to Figures 1, 2 and 3A-3G, an implantable fully bioabsorbable vascular polymer stent comprises five or more annular waved support rods 1 and a connection spaced apart from the support rod 1 support. The rod 2 is different from the embodiment 1 in that the width of the support rod and the connecting rod are different in the specific embodiment, the width of the support rod at the two ends of the bracket is the thickest, and the connection between the two ends of the bracket is The width of the rod is second, and then the width of the remaining support rods, and the width of the remaining connecting rods is the thinnest. Among them, the angle of the positive "s" and inverted "s" connecting segments is 40-45 degrees.

Example 4 An implantable fully bioabsorbable vascular polymer scaffold

Referring to Figures 1, 2 and 3A-3G, an implantable fully bioabsorbable vascular polymer stent comprises five or more annular waved support rods 1 and a connection spaced apart from the support rod 1 support. The rod 2 differs from the embodiment 1 in that the angle of the positive "s" and inverted "s" connecting segments is 10 degrees in the present embodiment; the angles of α1 and α2 in the class "Ω" are 130. Degree; the "m" shape has a β1 angle of 130 degrees and a β2 angle of 180 degrees; the angles γ1 and γ2 are both 5 degrees, the angles δ1 and δ2 are both 5 degrees; the "m"-shaped wave bottom and The angle η1 of the connecting rod ranges from 30 degrees, and the angle η2 of the "Ω"-shaped wave top and the connecting rod ranges from 30 degrees.

Example 5 An implantable fully bioabsorbable vascular polymer stent

Referring to Figures 1, 2 and 3A-3G, an implantable fully bioabsorbable vascular polymer stent comprises five or more annular waved support rods 1 and a connection spaced apart from the support rod 1 support. The rod 2 differs from the embodiment 1 in that the angle of the positive "s" and inverted "s" connecting segments is 30 degrees in the present embodiment; the angles of α1 and α2 in the class "Ω" are 180. Degree, the "m" shape of the β1 angle is 90 degrees, the β2 angle is 130 degrees; the angles γ1 and γ2 are both 30 degrees, the angles δ1 and δ2 are both 30 degrees; the class "m" wave bottom and The angle η1 of the connecting rod ranges from 0 degrees, and the angle η2 of the "Ω"-shaped wave top and the connecting rod ranges from 0 degrees.

Example 6 An implantable fully bioabsorbable vascular polymer scaffold

Referring to Figures 1, 2 and 3A-3G, an implantable fully bioabsorbable vascular polymer stent comprises five or more annular waved support rods 1 and a connection spaced apart from the support rod 1 support. The rod 2 differs from the embodiment 1 in that the angle of the positive "s" and inverted "s" connecting segments is 20 degrees in the present embodiment; the angles of α1 and α2 in the class "Ω" are 160. Degree, the "m" shape of the β1 angle is 100 degrees, the β2 angle is 150 degrees; the angles γ1 and γ2 angles are For 15 degrees, the angles δ1 and δ2 are both 15 degrees; the angle η1 of the "m" shaped wave bottom and the connecting rod ranges from 10 degrees, and the angle η2 of the "Ω" shaped wave top and the connecting rod ranges from 10 degrees. .

Example 7 An implantable fully bioabsorbable vascular polymer scaffold

Referring to Figures 1, 2, 3A-3G, 4A-4B, 5A-5B and 6A-6E, an implantable fully bioabsorbable vascular polymer stent comprising five or more annular waved support rods 1 And the connecting rod 2 which is connected to the support rod 1 bracket, which is different from the embodiment 4 in that, in the specific embodiment, the line connecting the "Ω"-shaped wave wave top and the wave bottom and the connecting rod The ratio of the length is 1, and the ratio of the line of the "m"-shaped wave wave top and the wave bottom to the length of the connecting rod is 1.

Example 8 An implantable fully bioabsorbable vascular polymer scaffold

Referring to Figures 1, 2, 3A-3G, 4A-4B, 5A-5B and 6A-6E, an implantable fully bioabsorbable vascular polymer stent comprising five or more annular waved support rods 1 And the connecting rod 2 which is connected to the support rod 1 bracket, and is different from the embodiment 5 in that, in the specific embodiment, the line connecting the "Ω"-shaped wave wave top and the wave bottom and the connecting rod The ratio of the length is 1.5, and the ratio of the line of the "m"-shaped wave wave top and the wave bottom to the length of the connecting rod is 1.5.

Example 9 An implantable fully bioabsorbable vascular polymer stent

Referring to Figures 1, 2, 3A-3G, 4A-4B, 5A-5B, 6A-6E and 7, an implantable fully bioabsorbable vascular polymer scaffold comprising five or more annular wave supports The rod 1 and the connecting rod 2 which are connected to the support rod 1 bracket are different from the embodiment 6 in that the connection and connection of the "Ω"-shaped wave top and the wave bottom are in the specific embodiment. The ratio of the length of the rod is 1.2, and the ratio of the line of the "m" shaped wave top and the wave bottom to the length of the connecting rod is 1.2. And the end rod width of the bracket is larger than the center rod width, and the end rod width of the bracket: the center rod width is about 1.1-1.2.

Wherein, the polymer stent of the foregoing Embodiments 1-9 has a radial strength of 240 kPa to 280 kPa when the inner diameter is 1.50 to 5.00 mm and the wall thickness is 0.05 to 0.2 mm, which fully satisfies the support strength of the stent. . Further preferably, the inner diameter is 2.50 to 4.00 mm, the wall thickness is 0.08 to 0.18 mm, and the radial strength is 250 kPa to 270 kPa, and the maximum control wall thickness is sufficiently thin.

In order to meet the requirements for implantation, the implantable fully bioabsorbable vascular polymer scaffold surface (including the medial or lateral side) is coated with a coating that inhibits the vascular stenosis or inhibits implant rejection, and the coated carrier has good Biocompatibility, effective treatment of vascular stenosis.

Example 10 Performance Test Protocol

Support strength test:

The polymer stents of Examples 1-9 were subjected to a uniform compression ratio extrusion, and when the force was significantly reduced or the diameter was reduced by at least 50%, the load and the associated diameter were recorded, and the corresponding axial unit axial length load was in accordance with Table 1. Requirements.

Table 1 bracket radial support strength

The results show that the radial support strength of the tested stents is in the range of 0.5 to 2.0 N/mm, which shows that the polymer stent has good supporting performance; among them, the embodiment 4-9 has better supporting performance. The unit axial length load is 1.0 to 2.0 N/mm; particularly, the embodiments 6 and 9 are superior, and are 1.5 N/mm and 1.8 N/mm, respectively.

Stability test

An implantable fully bioabsorbable vascular polymer scaffold of the present invention is stored at 40 ° C ± 2 ° C, 75% RH ± 5% RH and 25 ° C ± 2 ° C, 60% RH ± 5% RH Accelerate and real-time stability tests are performed. Current studies have shown that ideal degradable stents only need to support the vascular mechanical support during the specific time of injury healing, and are gradually absorbed by the body after giving sufficient mechanical support to the lesion segment and healing the lesion. For the specific time period of coronary stents, it is generally recognized that it is about half a year. Evaluation of the stability of support performance of an implantable fully bioabsorbable vascular polymer scaffold of the present invention during this time period, accelerated experiments and real-time stable results are shown in Tables 2 and 3, respectively.

Table 2 Accelerated Stability Test Results

Time (days)	Unit axial length load (N/mm)
11 (equivalent to 1 month in real time)	0.5～2.0
22 (equivalent to 2 months in real time)	0.5～2.0
32 (equivalent to 3 months in real time)	0.5～2.0
43 (equivalent to 4 months in real time)	0.5～2.0
54 (equivalent to 5 months in real time)	0.5～2.0
64 (equivalent to 6 months in real time)	0.5～2.0
75 (equivalent to 7 months in real time)	0.5～2.0
85 (equivalent to 8 months in real time)	0.5～2.0

96 (equivalent to 9 months in real time)

0.5～2.0

Table 3 real-time stability test results

Time (month)	Unit axial length load (N/mm)
1	0.5～2.0
2	0.5～2.0
3	0.5～2.0
4	0.5～2.0
5	0.5～2.0
6	0.5～2.0
7	0.5～2.0
8	0.5～2.0
9	0.5～2.0

The results show that the radial support strength of the tested stents is maintained at 0.5 to 2.0 N/mm for 9 months, which shows that the polymer stent has good support performance stability; Examples 4-9 different times The measured support force deviation is smaller, has better support stability, and the unit axial length load is still maintained at 1.0-2.0 N/mm, and the performance degradation begins to occur after the sixth month, especially in Example 6. Better than 9 and maintained at 1.5 to 1.8 N/mm and 1.8 to 2.0 N/mm, respectively, and performance degradation began to occur after the 7th month.

Example 10 Animal Experimental Protocol

Experimental method: healthy white pigs and healthy miniature pigs weighing 30-40 Kg and 6-8 months were implanted into the left anterior descending coronary artery, the circumflex artery and/or the right coronary artery, respectively. A polymer scaffold is implanted with 2 to 3 polymer scaffolds. Mainly concerned with the degree of endothelialization, thrombosis, etc. during a certain period of time.

As shown in Fig. 8, the results of the 30-day SEM showed that the polymer scaffold was substantially completely endothelialized; as shown in Fig. 9, the 0-day and 90-day OCT results showed that no thrombus was attached to the surface of the polymer scaffold, and the scaffold rod remained intact, and the endothelium remained intact. The coverage is good, no breakage occurs, and it is still clearly visible, which shows that the polymer support has good support performance and excellent stability. At the same time, the stents of Examples 4-9 have substantially uniform effects after implantation, especially in Examples 6 and 9.

Conclusion: It is found by animal experimental research that the polymer stent provided by the invention can not only provide sufficient mechanical support for the lesion segment within a certain time of injury healing, but is gradually absorbed by the body after the injury is healed, and the endothelialization is good and effectively reduced. The rate of stent restenosis and the risk of late stent thrombosis.

The above is a further detailed description of the present invention in conjunction with the specific preferred embodiments, but is not intended to limit the invention. It will be apparent to those skilled in the art that the present invention may be practiced without departing from the spirit and scope of the invention.

Claims (13)

1. An implantable fully bioabsorbable vascular polymer stent, comprising: more than five annular wave-shaped support rods, and a connecting rod spacedly connected between the support rods, the support rods of the brackets being of the class " The Ω"-shaped wave and the "m"-shaped wave are alternately connected, wherein the "Ω"-shaped wave and the "m"-shaped wave are respectively composed of two sets of positive "s" and inverted "s", respectively. The connection between the support rods is connected by a connecting rod at the "Ω"-shaped wave top and the "m"-shaped wave bottom, and the connecting rod is a straight rod.
2. An implantable fully bioabsorbable vascular polymer stent according to claim 1 wherein the angle of the positive "s" and inverted "s" connecting segments is between 5 and 45 degrees, preferably between 10 and 30 degrees.
3. An implantable fully bioabsorbable vascular polymer stent according to claim 1, wherein the angle "α1" of the "Ω" shaped wave crest ranges from 130 to 180 degrees, and the angle of the "Ω" shaped wave bottom is The range of α2 is 130 to 180 degrees; the angle β1 of the left or right wave top of the class "m" is in the range of 90 to 130 degrees; the angle β2 of the left or right wave of the "m" shape ranges from 130 to 180 degrees.
4. An implantable fully bioabsorbable vascular polymer stent according to claim 2, wherein the angle "α1" of the "Ω" shaped wave crest ranges from 130 to 180 degrees, and the angle of the "Ω" shaped wave bottom is The range of α2 is 130 to 180 degrees; the angle β1 of the left or right wave top of the class "m" is in the range of 90 to 130 degrees; the angle β2 of the left or right wave of the "m" shape ranges from 130 to 180 degrees.
5. An implantable fully bioabsorbable vascular polymer stent according to any one of claims 1 to 4, wherein the angle between the tangent of the "s" connecting point and the tangential line of the "Ω" shaped wave top arc The range of γ1 is 5 to 30 degrees, and the angle γ2 between the tangent of the "s" connection point and the tangential line of the "Ω"-shaped wave bottom is 5 to 30 degrees; the tangent of the "s" connection point and the class "m" The angle δ1 of the apex of the wave-arc arc is 5 to 30 degrees, and the angle δ2 between the tangent of the "s" connection point and the tangent of the "m"-shaped wave bottom is 5 to 30 degrees.
6. An implantable fully bioabsorbable vascular polymer stent according to any one of claims 1 to 4, wherein the angle η1 of the "m" shaped wave bottom and the connecting rod ranges from 0 to 30 degrees. The angle η2 of the "Ω"-shaped wave top and the connecting rod is in the range of 0 to 30 degrees.
7. The implantable fully bioabsorbable vascular polymer stent according to claim 5, wherein the angle η1 of the "m" shaped wave bottom and the connecting rod ranges from 0 to 30 degrees; The angle η2 between the wave top and the connecting rod ranges from 0 to 30 degrees.
8. An implantable fully bioabsorbable vascular polymer stent according to any one of claims 1-7, characterized in that the line connecting the "Ω"-shaped wave wave top and the wave bottom and the length of the connecting rod The ratio ranges from 0.5 to 2, preferably from 0.8 to 1.5; the ratio of the line connecting the "m" shaped wave top to the bottom of the wave to the length of the connecting rod ranges from 0.5 to 2, preferably from 0.8 to 1.5.
9. An implantable fully bioabsorbable vascular polymer stent according to any one of claims 1-8, wherein the width of the support rod and the connecting rod are the same or different; the width of the support rod at both ends of the bracket and the bracket Middle part of the support rod The widths are the same or different; the width of the connecting rods at the ends of the bracket is the same as or different from the width of the connecting rods in the middle portion of the bracket.
10. The implantable fully bioabsorbable vascular polymer stent according to any one of claims 1-9, wherein the thin-walled tube has an inner diameter of 1.50 to 5.00 mm and a wall thickness of 0.05 to 0.2 mm. The radial strength is 240 kPa to 280 kPa; the inner diameter is preferably 2.50 to 4.00 mm, the wall thickness is 0.08 to 0.18 mm, and the radial strength is 250 kPa to 270 kPa.
11. An implantable fully bioabsorbable vascular polymer stent according to claim 10, wherein said polymer stent has a load per unit axial length of from 0.5 to 2.0 N/mm, preferably from 1.0 to 2.0 N/mm. .
12. An implantable fully bioabsorbable vascular polymer scaffold according to any one of claims 1-11, wherein the material composition of the polymer scaffold preferably comprises the following polymers: polylactic acid, L-poly One or both of lactic acid, DL-polylactic acid, polyglycolic acid, polycaprolactone, or a mixture thereof.
13. An implantable fully bioabsorbable vascular polymer scaffold according to claim 12, wherein said polymer scaffold surface is coated with a drug-loaded coating, said coated carrier comprising: left-handed poly Lactic acid, polylactic acid-glycolic acid copolymer, racemic polylactic acid, polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, PVP, polyxylitol, polyglycerol ester, sodium alginate , chitosan, chitin, dextran, poly-hard acid ester, poly-citrate, etc.; the drug includes anti-oxidation drugs, anti-coagulant drugs, anti-cancer drugs, inhibiting vascular smooth muscle cell proliferation drugs One or more of an anti-inflammatory drug or an immunosuppressive drug.

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