WO2023178938A1

WO2023178938A1 - 3d-printed degradable intravascular stent loaded with salvianolic acid b

Info

Publication number: WO2023178938A1
Application number: PCT/CN2022/117983
Authority: WO
Inventors: 王武
Original assignee: 苏州卓欣雅科技有限公司
Priority date: 2022-03-23
Filing date: 2022-09-09
Publication date: 2023-09-28
Also published as: CN114470344A

Abstract

A 3D-printed degradable intravascular stent loaded with salvianolic acid B, comprising a first supporting ring (1), a second supporting ring (2), and a supporting rod (3). The second supporting ring (2) is arranged on the side of the first supporting ring (1), and one end of the first supporting ring (1) and one end of the second supporting ring (2) are connected with the other first supporting ring (1) and the other second supporting ring (2) by means of the supporting rod (3). The first support ring (1) comprises a movable chamber (110) provided inside the first support ring (1), and a plurality of first latches (120) are fixed at the other end of the first support ring (1). By means of a first drug storage chamber (410), a second drug storage chamber (420), and a central core drug storage chamber (430), the outermost layer of a support mesh frame (4) is damaged during the degradation process, such that a salvianolic acid B drug in the first drug storage chamber (110) flows out, thereby treating the vascular wound site. In the subsequent degradation process, the salvianolic acid B drugs in the second drug storage chamber (420) and the central core drug storage chamber (430) sequentially flow out to treat the wound blood vessel, so that the effect of staged blood vessel treatment is achieved.

Description

[Invention title established by ISA under Rule 37.2] 3D printed degradable intravascular stent loaded with salvianolic acid B

Technical field

The invention relates to a medical device, in particular to a 3D printed degradable intravascular stent loaded with salvianolic acid B.

Background technique

Vascular stent implantation is a mechanical interventional treatment. For example, coronary stent implantation is the most effective method to deal with acute vascular occlusion, that is, a balloon catheter is inserted into a narrowed blood vessel through blood vessel puncture, and the stent is released at the coronary artery lesion through balloon expansion, opening the narrowed blood vessel wall and providing Continuous support to maintain the openness and smoothness of the coronary lumen and reduce the mortality rate of acute myocardial infarction.

Clinical requirements for the mechanical properties of coronary stents are very high. They must have sufficient strength and fatigue performance to maintain the support of the stent on the blood vessel wall, and also need good flexibility to ensure operability during surgery. However, existing vascular stents have problems such as low resistance to uncertain stress and poor support stability. At the same time, when releasing loaded drugs, existing stents have problems such that drug release is not convenient and smooth enough, and cannot be released in stages.

Contents of the invention

The present invention overcomes the shortcomings of the existing technology and provides a 3D printed degradable intravascular stent loaded with salvianolic acid B.

In order to achieve the above purpose, the technical solution adopted by the present invention is: a 3D printed degradable intravascular stent loaded with salvianolic acid B, including: a first support ring, a second support ring and a support rod. The second support ring Disposed on the side of the first support ring, one end of the first support ring and the second support ring is connected to another first support ring and another second support ring through a support rod;

The first support ring includes a movable cavity opened inside the first support ring, and a plurality of first teeth are fixed at the other end of the first support ring;

The second support ring includes a plurality of second teeth fixed on one end of the second support ring, and a cavity that is the same as the movable cavity is provided inside the second support ring;

Both ends of the support rod are respectively inserted into the interior of the movable cavity. The first support ring and the second support ring are meshed with each other through the first teeth and the second teeth, and are arranged in an annular shape. The cloth forms a closed loop.

In a preferred embodiment of the present invention, support grids are fixed on the sides of the first support ring and the second support ring. The materials of the first support ring, the second support ring, the support rods and the support grid are All are degradable materials.

In a preferred embodiment of the present invention, the support grid includes a first medicine storage chamber, a second medicine storage chamber and a central medicine storage chamber.

In a preferred embodiment of the present invention, the first medicine storage chamber, the second medicine storage chamber and the central medicine storage chamber all store salvianolic acid B medicine inside.

In a preferred embodiment of the present invention, the number and position of the first latching teeth and the second latching teeth match.

In a preferred embodiment of the present invention, a through hole is provided on the surface of the movable cavity, and the diameter of the through hole matches the diameter of the support rod.

In a preferred embodiment of the present invention, a chute is provided on the inner wall of the movable cavity, a slider is fixed on the surface of the support rod, and the slider is slidably connected in the chute. Both the slider and the chute have two , and set symmetrically.

In a preferred embodiment of the present invention, the first support ring, the second support ring, the support rod and the support grid are made of degradable polycaprolactone, polyurethane or polylactic acid.

In a preferred embodiment of the present invention, the surfaces of the first support ring, the second support ring and the support grid are all coated with anticoagulant drugs, which are enoxaparin sodium, nadroparin calcium, dalteparin sodium, Any antithrombotic drug among aspirin, clopidogrel, ticlopidine, dipyridamole, urokinase, and streptokinase.

In a preferred embodiment of the present invention, the first support ring, the second support ring and the support grid are all prepared by 3D printing, and the printing method is rotational layer-by-layer forming.

The present invention solves the defects existing in the background technology and has the following beneficial effects:

(1) The present invention provides support to diseased blood vessels immediately after implantation and effectively inhibits restenosis; at the same time, during the degradation process, the medicine in the medicine storage cavity can treat blood vessels in stages, improving the therapeutic effect, and when the blood vessel repair is completed Afterwards, the stent is directly degraded completely and the normal physiological functions of blood vessels are restored.

(2) The present invention uses the first support ring, the second support ring and the support rod to enable the stent to provide support to the diseased blood vessel immediately after being expanded by the balloon, effectively inhibiting restenosis. At the same time, between the first latch and the With the cooperation of the second latching teeth, the stent can be fixed twice to avoid direct retraction under the pressure of the blood vessel wall, thereby preventing the stent from deforming and affecting the treatment effect.

(3) In the present invention, through the first medicine storage cavity, the second medicine storage cavity and the central medicine storage cavity, the outermost layer of the support grid is damaged during the degradation process, so that the salvianolic acid B drug in the first medicine storage cavity is flow out, thereby treating the injured part of the blood vessel. During the subsequent degradation process, the salvianolic acid B drug in the second drug storage chamber and the central core drug storage chamber flows out sequentially to treat the injured blood vessel, thereby achieving staged treatment. The effect of treating injured blood vessels. Salvianolic acid B is a condensation of three molecules of salvianoside and one molecule of caffeic acid. It has a delayed protective effect on cardiac microvascular endothelial cells and a preventive and therapeutic effect on atherosclerosis.

(4) In the present invention, the salvianolic acid B drug in the drug storage cavity is wrapped into a ball through existing technology, and dissolves and ruptures after being released from the blood. After the drug ball ruptures, the surrounding blood quickly occupies the position of the drug ball and collides with each other. Forming an impact to micro-clear the thrombus on the diseased vessel wall, thereby achieving a certain therapeutic effect and further improving the therapeutic ability of the device

(5) The present invention obtains the morphological structure of the diseased blood vessel, designs the shape of the vascular stent in a personalized manner, and refines the shape of the vascular stent, establishes a three-dimensional model for preparing the vascular stent, and prepares the vascular stent through 3D printing equipment; so that the vascular stent can be compared It is well adapted to the patient's blood vessels; at the same time, the stent body is made of degradable material, which can be degraded in the patient's body and reduce sequelae.

Description of the drawings

In order to explain the embodiments of the present invention or the technical solutions in the prior art more clearly, the drawings needed to be used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings in the following description are only These are some embodiments recorded in the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without exerting creative efforts;

Figure 1 is a three-dimensional structural view of a preferred embodiment of the present invention;

Figure 2 is a front cross-sectional structural view of a preferred embodiment of the present invention;

Figure 3 is a top cross-sectional structural view of a preferred embodiment of the present invention;

Figure 4 is an enlarged structural view of position A in Figure 2 of the preferred embodiment of the present invention;

Figure 5 is an enlarged structural view of B in Figure 3 of the preferred embodiment of the present invention;

Figure 6 is a partial cross-sectional structural view of the support grid according to the preferred embodiment of the present invention;

In the figure: 1. First support ring; 110. Movable cavity; 120. First latching teeth; 130. Slide groove; 140. Through hole; 2. Second support ring; 210. Second latching teeth; 3. Support rod ; 310. Slider; 4. Support grid; 410. First medicine storage chamber; 420. Second medicine storage chamber; 430. Central core medicine storage chamber.

Detailed ways

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. In the description of the present invention, the words "embodiment", "one embodiment" or "other embodiments" Reference means that a particular feature, structure or characteristic described in connection with the embodiments is included in at least some, but not necessarily all, embodiments. If the specification describes a component, feature, structure, or characteristic that "may," "might," or "could" be included, that particular component, feature, structure, or characteristic does not necessarily need to be included. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the scope of protection of the present invention.

In the description of the present invention, it should be understood that the terms "center", "longitudinal", "lateral", "upper", "lower", "front", "rear", "left", "right", " The orientations or positional relationships indicated by "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. are based on the orientations or positional relationships shown in the drawings, and are only for the convenience of describing the present invention and The simplified description does not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operate in a specific orientation, and therefore cannot be construed as limiting the scope of the present invention.

As shown in Figures 1, 2 and 3, a salvianolic acid B-loaded 3D printed degradable intravascular stent includes: a first support ring 1, a second support ring 2 and a support rod 3. The second support ring 2 is arranged on the side of the first support ring 1. One end of the first support ring 1 and the second support ring 2 is connected to another first support ring 1 and another second support ring 2 through a support rod 3; the present invention is implanted It immediately provides support to the diseased blood vessels and effectively inhibits restenosis; at the same time, during the degradation process, the drugs in the drug storage cavity can treat the blood vessels in stages to improve the therapeutic effect. When the blood vessel repair is completed, the stent will directly degrade completely and restore the normal physiological function of blood vessels.

As shown in Figures 3 and 5, the first support ring 1 includes a movable cavity 110 opened inside the first support ring 1. A plurality of first teeth 120 are fixed at the other end of the first support ring 1. The second support ring 2 , including a number of second latching teeth 210 fixed at one end of the second support ring 2. The number and position of the first latching teeth 120 and the second latching teeth 210 match. The second support ring 2 is provided with the same movable cavity 110 inside. The two ends of the support rod 3 are respectively inserted into the movable cavity 110. The first support ring 1 and the second support ring 2 are engaged with the first latching teeth 120 and the second latching teeth 210, and are arranged in an annular shape to form Closed loop; the present invention uses the first support ring 1, the second support ring 2 and the support rod 3, so that the stent can immediately provide support to the diseased blood vessel after being expanded by the balloon, effectively inhibiting restenosis. At the same time, after the first stuck With the cooperation of the teeth 120 and the second latch teeth 210, the stent can be fixed twice to avoid direct retraction under the pressure of the blood vessel wall, thereby preventing the stent from deforming and affecting the treatment effect.

As shown in Figure 6, a support grid 4 is fixed on the sides of the first support ring 1 and the second support ring 2. The support grid 4 includes a first medicine storage chamber 410, a second medicine storage chamber 420 and a central medicine storage chamber. Chamber 430, the first medicine storage chamber 410, the second medicine storage chamber 420 and the central medicine storage chamber 430 all store salvianolic acid B medicine inside; the present invention uses the first medicine storage chamber 410, the second medicine storage chamber 420 and the In the central medicine storage cavity 430, the outermost layer of the support grid 4 is damaged during the degradation process, causing the salvianolic acid B drug in the first medicine storage cavity 410 to flow out, thereby treating the injured part of the blood vessel, and in the subsequent degradation process , the salvianolic acid B medicine in the second medicine storage chamber 420 and the central medicine storage chamber 430 flows out sequentially to treat the injured blood vessels, thereby achieving the effect of treating the injured blood vessels in stages, wherein the salvianolic acid B is It is formed by the condensation of three molecules of Danshensu and one molecule of caffeic acid, which has a delayed protective effect on cardiac microvascular endothelial cells and a preventive and therapeutic effect on atherosclerosis.

As shown in Figure 4, a through hole 140 is provided on the surface of the movable chamber 110. The diameter of the through hole 140 matches the diameter of the support rod 3. A slide groove 130 is provided on the inner wall of the movable chamber 110. A slider 310 is fixed on the surface of the support rod 3. The slider 310 is slidingly connected in the chute 130. There are two sliders 310 and two chute 130, and they are arranged symmetrically. This avoids the problem of the support rod 3 detaching from the movable cavity 110 when the bracket is rapidly expanded, thereby improving the overall support effect. , at the same time, the slider 310 and the chute 130 can also provide support and guidance for the first support ring 1 and the second support ring 2 during expansion.

The surfaces of the first support ring 1, the second support ring 2 and the support grid 4 are all coated with anticoagulant drugs, which are enoxaparin sodium, nadroparin calcium, dalteparin sodium, aspirin, clopidogrel, tetrachloride Any anti-thrombotic drug such as dipyridamole, urokinase or streptokinase; the surface of the stent is coated with anti-coagulant drugs, which can prevent the body from treating the stent as a foreign body and prevent the aggregation of red blood cells and the occurrence of thrombosis. .

The first support ring 1, the second support ring 2, the support rod 3 and the support grid 4 are all made of degradable materials. The first support ring 1, the second support ring 2 and the support grid 4 are all prepared by 3D printing. The printing method is rotational layer-by-layer molding; by obtaining the morphological structure of the diseased blood vessel, the shape of the vascular stent is personalized, and the shape of the vascular stent is customized, a three-dimensional model for preparing the vascular stent is established, and the vascular stent is prepared through 3D printing equipment; so that The vascular stent can better adapt to the patient's blood vessels; the first support ring 1, the second support ring 2, the support rod 3 and the support grid 4 are made of degradable polycaprolactone, polyurethane or polylactic acid, and the stent body is made of biodegradable polycaprolactone, polyurethane or polylactic acid. Degradable materials can be degraded in the patient's body, reducing sequelae

When the present invention is used, the morphological data of the diseased blood vessel is first obtained, the length of the vascular stent is determined through three-dimensional reconstruction, a three-dimensional model of the blood vessel stent is established in the computer, and the three-dimensional model is decomposed into a two-dimensional thin slice model of 10-30um. Import the model data into the 3D printing equipment, add degradable materials to the 3D printing equipment, then start the 3D printing equipment, perform 3D printing, and prepare vascular stents

Then, the device is compressed on the surface of the inflatable balloon, and then the medical staff will place the inflatable balloon carrying the device at the narrowed part of the blood vessel, and then expand the stent through the balloon as needed. Under the thrust of the balloon downward, the first support ring 1, the second support ring 2 and the support rod 3 expand, thereby stretching the blood vessel wall. At the same time, the first support ring 1 and the second support ring 2 drive the first latch 120 during the expansion process. With the relative movement of the second latch 210, at the same time, with the cooperation of the support rod 3, the slider 310 and the chute 130, the first support ring 1 and the second support ring 2 can be fixed to avoid the pressure of the stent on the blood vessel wall. Lower retraction.

The surface of the stent is coated with anticoagulant drugs, which can prevent the human body from treating the stent as a foreign body, and at the same time avoid the aggregation of red blood cells and the occurrence of thrombus. During use, the stent gradually degrades, and the outermost layer of the support grid 4 appears during the degradation process. Damage causes the salvianolic acid B drug 5 in the first drug storage chamber 410 to flow out, thereby treating the injured part of the blood vessel. Similarly, during the subsequent degradation process, the second drug storage chamber 420 and the central core drug storage chamber 430 The salvianolic acid B drug in the drug flows out in sequence to treat the injured blood vessels, thereby achieving the effect of treating the injured blood vessels in stages. Salvianolic acid B is the condensation of three molecules of salvianoside and one molecule of caffeic acid. It has the effect of treating injured blood vessels. Delayed protective effect of cardiac microvascular endothelial cells and prevention and treatment of atherosclerosis.

In the description of the present invention, it should be noted that, unless otherwise clearly stated and limited, the terms "installation", "connection" and "connection" should be understood in a broad sense. For example, it can be a fixed connection or a detachable connection. Connection, or integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium; it can be an internal connection between two components. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood through specific situations.

The above is based on the ideal embodiment of the present invention. Through the above description, relevant personnel can make various changes and modifications without departing from the scope of the technical idea of the present invention. The technical scope of the present invention is not limited to the content in the description, and must be determined based on the scope of the claims.

Claims

A 3D printed degradable intravascular stent loaded with salvianolic acid B, including: a first support ring, a second support ring and a support rod, characterized in that: the second support ring is provided on the side of the first support ring, so One end of the first support ring and the second support ring is connected to another first support ring and another second support ring through a support rod;

The first support ring includes a movable cavity opened inside the first support ring, and a plurality of first teeth are fixed at the other end of the first support ring;

The second support ring includes a plurality of second teeth fixed on one end of the second support ring, and a cavity that is the same as the movable cavity is provided inside the second support ring;

Both ends of the support rod are respectively inserted into the interior of the movable cavity. The first support ring and the second support ring are meshed with each other through the first teeth and the second teeth, and are arranged in an annular shape. The cloth forms a closed loop.
A 3D printed degradable intravascular stent loaded with salvianolic acid B according to claim 1, characterized in that: both the first support ring and the second support ring have support grids fixed on their sides, and the The first support ring, the second support ring, the support rod and the support grid are all made of degradable materials.
A 3D printed degradable intravascular stent loaded with salvianolic acid B according to claim 2, characterized in that: the support grid includes a first medicine storage chamber, a second medicine storage chamber and a central core medicine storage chamber. cavity.
A 3D printed degradable intravascular stent loaded with salvianolic acid B according to claim 3, characterized in that: the first drug storage chamber, the second drug storage chamber and the central core drug storage chamber all store Salvianolic acid B drug.
A 3D printed degradable intravascular stent loaded with salvianolic acid B according to claim 1, characterized in that the number and position of the first latching teeth and the second latching teeth match.
A 3D printed degradable intravascular stent loaded with salvianolic acid B according to claim 1, characterized in that: a through hole is provided on the surface of the movable chamber, and the diameter of the through hole matches the diameter of the support rod. .
A 3D printed degradable intravascular stent loaded with salvianolic acid B according to claim 1, characterized in that: a chute is provided on the inner wall of the movable chamber, a slider is fixed on the surface of the support rod, and the slider slides Connected in the chute, there are two slide blocks and two chute, and they are arranged symmetrically.
A 3D printed degradable intravascular stent loaded with salvianolic acid B according to claim 1, characterized in that: the first support ring, the second support ring, the support rod and the support grid are made of degradable polyethylene. Preparation from caprolactone, polyurethane or polylactic acid.
A 3D printed degradable intravascular stent loaded with salvianolic acid B according to claim 1, characterized in that: the surfaces of the first support ring, the second support ring and the support grid are all coated with anticoagulant drugs , and it is any antithrombotic drug among enoxaparin sodium, nadroparin calcium, dalteparin sodium, aspirin, clopidogrel, ticlopidine, dipyridamole, urokinase, and streptokinase.
A 3D printed degradable intravascular stent loaded with salvianolic acid B according to claim 1, characterized in that: the first support ring, the second support ring and the support grid are all prepared by 3D printing, and the printing The method is to rotate and form layer by layer.