An artificial blood vessel for reducing stenosis of vascular anastomosis and a preparation method thereof

Abstract

The present invention discloses an artificial blood vessel for reducing the stenosis of the vascular anastomosis and a preparation method thereof, and relates to the technical field of artificial blood vessel manufacturing. The artificial blood vessel provided by the present invention comprises an artificial blood vessel body, a suture ring, a covering film and a support ring; the covering film is a cylindrical structure, one end of the covering film is connected to the end of the artificial blood vessel body, and the other end is provided with the support ring; the suture ring is located at the end of the artificial blood vessel body, and the covering film is located inside the suture ring; the outer diameter of the support ring is at least 1 times the inner diameter of the artificial blood vessel body; the covering film is made of a flexible elastic material. The present invention provides an artificial blood vessel with a special structure, which utilizes the synergistic effect of the suture ring, the covering film and the support ring to not only improve the support effect on the anastomosis, but also effectively reduce the problem of anastomotic stenosis.

Description

Technical Field

[0001] The invention relates to the technical field of artificial blood vessel manufacturing, in particular to an artificial blood vessel for reducing stenosis of blood vessel anastomosis. Background Art

[0002] Artificial blood vessels (artificial blood vessels) are a commonly used substitute for biological blood vessels with severe stenosis or occlusion. Artificial blood vessels are mostly made of polymer materials such as polyurethane, nylon, polyester (Dacron), polytetrafluoroethylene (PTFE), etc., and are suitable for vascular bypass surgery throughout the body. Large, medium and micro-caliber artificial blood vessels have been used in clinical practice and have achieved satisfactory results.

[0003] When suturing an artificial blood vessel, first use a scalpel to make an incision on the side wall of the original blood vessel of the human body / animal body, and then sew the artificial blood vessel to the incision; or, sew the end of the original blood vessel of the human body / animal body directly to the end of the artificial blood vessel. The sutured site is the anastomosis. After suturing in this way, it is easy to have stenosis problems at the anastomosis at the proximal end, which is a common adverse condition in clinical practice. Anastomotic stenosis is caused by the suture of vascular tissue and artificial blood vessels (anastomosis). Since artificial blood vessels are made of materials different from biological bodies, the organism will produce a self-protection mechanism to try to weaken the impact of foreign bodies, and produce tissue hyperplasia similar to biological scars near the anastomosis, resulting in anastomotic stenosis. Anastomotic stenosis will affect the normal flow of blood into the artificial blood vessel and in the artificial blood vessel, and form thrombi in the anastomosis and artificial blood vessels.

[0004] In order to reduce or avoid the problem of anastomotic stenosis, the traditional method is to use a high-pressure balloon to expand the blocked anastomosis after the problem of anastomotic stenosis occurs, or to place a vascular stent again. The disadvantage of doing so is that a secondary operation will be performed, which increases the cost and causes secondary physiological, psychological and economic burdens on the patient. At present, there is also a method of setting a reinforcing ring or a supporting ring at the proximal end of the artificial blood vessel (the end sutured with the animal blood vessel) to play the purpose of expanding support. Although this structure supports the anastomosis, it is still impossible to avoid the proliferation of vascular wall cells at the anastomosis to the inside of the anastomosis, that is, the problem of anastomotic stenosis cannot be solved. Summary of the invention

[0005] In view of the deficiencies of the above prior art, the present invention provides an artificial blood vessel that reduces the stenosis of the vascular anastomosis. By setting a special suture ring, a covering film and a supporting ring structure at the proximal end of the artificial blood vessel, the artificial blood vessel is sutured through surgery. The covering film isolates the blood at the suture site from the contact between the suture thread stitches and the suture site, thereby reducing the tendency of the cells of the vascular wall to proliferate inside the anastomosis, and effectively reducing the probability of anastomotic stenosis after surgical suture of the artificial blood vessel. Only one artificial blood vessel suture operation is required, and there is no need to worry about subsequent secondary operations. It is specifically achieved through the following technologies.

[0006] An artificial blood vessel for reducing stenosis of vascular anastomosis comprises an artificial blood vessel body, a suture ring, a covering film and a support ring; the covering film is a cylindrical structure, one end of the covering film is connected to the end of the artificial blood vessel body, and the other end is provided with the support ring; the suture ring is located at the end of the artificial blood vessel body, and the covering film is located inside the suture ring; the outer diameter of the support ring is not less than the inner diameter of the artificial blood vessel body; the covering film is made of flexible elastic material.

[0007] The above-mentioned artificial blood vessel provided by the present invention is a support ring connected to the proximal end of the artificial blood vessel body through a covering film, and the suture ring is also located at the proximal end of the artificial blood vessel body. The method of using the above-mentioned artificial blood vessel is as follows: (1) an incision is made at the surgical site of a human or animal blood vessel (hereinafter referred to as "biological blood vessel") to obtain an anastomosis; (2) the covering film and the support ring are inserted into the anastomosis to enter the interior of the biological blood vessel; (3) the biological blood vessel is sutured around the suture ring using a non-degradable suture thread, at which time the suture ring is attached to the anastomosis, and the proximal end of the artificial blood vessel has been tightly sutured with the biological blood vessel; (4) the support ring together with the covering film is folded toward the interior of the artificial blood vessel, so that the support ring and the covering film enter the interior of the artificial blood vessel, the covering film is unfolded and attached to the inner wall of the artificial blood vessel, and the support ring plays a supporting role inside the artificial blood vessel, thus completing the suturing process of the artificial blood vessel.

[0008] By using the artificial blood vessel and the corresponding suturing method of the present application, the suturing ring and the supporting ring can both improve the suturing strength and provide good support to the anastomotic site at the outside and inside of the anastomotic site, respectively. The covering film can separate the area near the anastomotic site from the blood, making the blood flow channel of the anastomotic site smooth and unobstructed. The covering film also has a certain mechanical support force, which also serves the purpose of expanding the anastomotic site.

[0009] In the above-mentioned artificial blood vessel structure provided by the present invention, the artificial blood vessel body can be selected from the common artificial blood vessel products currently on the market or manufactured using commonly used technologies, and uses materials with good biocompatibility, which will not have adverse effects on the blood vessels and organisms of the organism. In order to enable the support ring to eventually enter the interior of the artificial blood vessel to play a supporting function, the outer diameter of the support ring cannot be too small, otherwise it will affect the blood flow rate in the artificial blood vessel and cause thrombosis; the outer diameter of the support ring is slightly larger than the inner diameter of the artificial blood vessel body, which will not only not affect the support performance of the support ring, but also expand the inner wall of the artificial blood vessel body to play a better supporting role. In order to facilitate the artificial blood vessel to complete suturing and play their respective functions using the above-mentioned surgical process, the suturing ring and the support ring are composed of materials with a certain elastic deformation ability, and can quickly restore the original shape and provide corresponding support; the covering film must also be made of a flexible elastic material.

[0010] At present, there are also some patents that provide structures for reducing anastomotic stenosis (e.g., CN116869591A). However, most of these structures are too large, the surgical suture wound surface after implantation in the organism is too large, the structure is too complicated, and the surgical suturing process is very complicated; the bigger problem is that the suture line and the incision of the biological blood vessel are in contact with the blood, and there is still a risk of secondary stenosis of the anastomosis. The artificial blood vessel structure of the present invention is simpler, requires less suturing operations, and greatly reduces the risk of postoperative anastomotic stenosis.

[0011] Furthermore, the length of the covering film is 2-4 times the thickness of the suture ring. Generally speaking, the covering film is mainly used to separate the anastomosis from the blood, so the length of the covering film is longer than the thickness of the suture ring, and the length of the covering film ultimately determines the position of the support ring in the artificial blood vessel body, and then determines the distance between the support ring and the anastomosis. If the distance is too large, the support ring cannot support the anastomosis, and the meaning of its setting is lost. If the distance is too small, the covering film may not completely cover the suture. Generally speaking, the inner diameter of the artificial blood vessel body is different, and the length of the covering film will be adjusted accordingly.

[0012] It should be noted that when the anastomosis is located on the side wall of the biological blood vessel, the artificial blood vessel provided by the present invention can be sutured at a certain tilt angle θ (such as 45°, 60°, etc.) commonly used in the industry, or at an angle approximately perpendicular to the artificial blood vessel and the biological blood vessel. When sutured in an inclined manner, the anastomosis is in an elliptical shape, and the suture ring fits the anastomosis in order to ensure the suture effect, so it is also in an elliptical shape; the plane where the support ring is located must still maintain an approximately perpendicular relationship with the axial direction of the artificial blood vessel. In order to achieve this vertical relationship between the support ring and the support ring, the port where the covering film is connected to the main part of the artificial blood vessel must be elliptical, and one side of the covering film is longer (i.e., the long side) and one side is shorter (i.e., the short side). If the length of the long side is L and the length of the long side is l, i.e., L>l, the requirement for the length of the covering film in the present invention generally refers to the shorter length of l, and it must satisfy Δl=(Ll)=D / tanθ, where D is the inner diameter (diameter) of the artificial blood vessel.

[0013] Furthermore, the width of the sewing ring is 1-3 times the total wall thickness of the artificial blood vessel body. The width of the sewing ring (i.e., the thickness of the sewing ring) will affect the suturing effect. If the sewing ring is too thick, it will be difficult for the organism to tolerate it; if the sewing ring is too thin, it will lead to insufficient support force and fail to play a supporting role, and the difficulty of surgical suturing will increase. Generally speaking, the size and wall thickness of the artificial blood vessel body are different, and the width of the sewing ring will be adjusted accordingly.

[0014] Furthermore, the ring width of the support ring is no more than 0.8 times the total wall thickness of the artificial blood vessel body. Since the support ring is located inside the artificial blood vessel body to play a supporting role, the ring width of the support ring will affect the supporting performance and blood flow rate.

[0015] Furthermore, the suture ring and the support ring are made of at least one material selected from polyurethane, memory metal, polytetrafluoroethylene, silicone rubber and polyolefin, all of which have certain mechanical properties and are easy to suture the suture ring.

[0016] Furthermore, a suture layer is provided on the outside of the suture ring, and the suture layer is composed of at least one material selected from the group consisting of polyurethane, expanded polytetrafluoroethylene, silicone rubber, and polyolefin.

[0017] When the suture ring is made of memory metal, a suture layer for medical suture needs to be coated on the outside, which is conducive to suturing and providing support. When the suture ring is made of polyurethane or silicone rubber, it is generally not necessary to add a suture layer. Of course, adding a suture layer is more conducive to suturing and providing support.

[0018] Furthermore, the covering film is composed of at least one of polyurethane, silicone rubber, expanded polytetrafluoroethylene, and polyolefin, all of which have good flexibility, elasticity, and certain support.

[0019] Furthermore, the outside of the sewing ring and / or the supporting ring is also coated with a silicone layer and / or an anticoagulant layer. The coating is provided mainly to take into account the requirements of anticoagulation of the artificial blood vessel and improving biocompatibility. When the sewing ring and / or the supporting ring are made of certain materials that are prone to aging (such as polyurethane, etc.), in order to reduce the risk of aging, a silicone layer can be coated on the surface of the sewing ring and / or the supporting ring, which can effectively avoid degradation problems and ensure stable support performance.

[0020] Furthermore, the surface of the covering film is loaded with a functional coating, and the functional coating is composed of at least one of polyethyleneimine, phosphorylcholine, dextran sulfate, and heparin sodium. These materials can improve the biocompatibility of the covering film and can also be coated with sustained-release drugs, etc. By providing a functional coating, the probability of stenosis at the anastomotic site can be further reduced. Generally, the functional coating can be applied using the currently available method.

[0021] Furthermore, the end of the artificial blood vessel is protruded relative to the suture ring, and the protruding length is 0.5-1.5 times the total wall thickness of the artificial blood vessel. In order to achieve a better suturing effect between the artificial blood vessel and the biological blood vessel, the protruding part of the end of the artificial blood vessel is deeply inserted into the anastomosis. The protruding length of the protruding part varies with the total wall thickness of the artificial blood vessel. It cannot be too long to affect blood flow, nor too short to have no effect.

[0022] The present invention also provides a method for preparing the artificial blood vessel, which is implemented by any one of the following two methods; the first method comprises the following steps:

[0023] P1. preparing the inner layer of the artificial blood vessel;

[0024] P2. Sleeve the inner layer on the mold, sleeve the sewing ring at a predetermined position of the inner layer, and sleeve the support ring at a predetermined position of the mold; the support ring is arranged away from the inner layer;

[0025] P3. A layer of elastic dense layer is disposed on the outer surface of the inner layer, on the sewing ring and the support ring, and on the entire surface of the mold between the sewing ring and the support ring; the elastic dense layer formed between the support ring and the sewing ring is the covering film;

[0026] P4, disposing an outer layer outside the elastic dense layer corresponding to the inner layer and the suture ring, demoulding, and obtaining the artificial blood vessel;

[0027] Furthermore, the first method for preparing the artificial blood vessel is:

[0028] (1) taking a spinning solution and forming the inner layer of the artificial blood vessel by electrospinning;

[0029] (2) The inner layer, the sewing ring and the support ring are placed on the rod column mold, the sewing ring is placed at the port on the outer surface of the inner layer, and the support ring is placed at a predetermined distance from the sewing ring;

[0030] (3) electrospray coating a dense silicone layer (i.e., an elastic dense layer) on the outer surface of the inner layer, the sewing ring and the support ring, and the portion between the sewing ring and the support ring;

[0031] The silicone layer completely wraps the sewing ring and the support ring, and forms a thin film (i.e., a covering film) to connect the sewing ring and the support ring together;

[0032] (4) The outer layer of the blood vessel is prepared by electrospinning on the outer surface of the dense layer, and the outer layer of the blood vessel covers the inner layer of the blood vessel and the suture ring.

[0033] Alternatively, the second method includes the following steps:

[0034] Q1. The sewing ring, the covering film and the supporting ring are prepared as a whole, wherein the covering film is located between the sewing ring and the supporting ring;

[0035] Q2. Suture the suture ring to one end of the artificial blood vessel body, and set the covering film and the support ring away from the artificial blood vessel body to obtain the artificial blood vessel.

[0036] Furthermore, the second method for preparing the artificial blood vessel is:

[0037] Ⅰ. Taking the spinning solution and preparing the artificial blood vessel inner layer, elastic dense layer and outer layer (i.e. the artificial blood vessel body) by electrospinning;

[0038] II. Prepare a silica gel solution, fix the sewing ring and the support ring at the predetermined position on the appropriate rod column mold to form the mold as a whole;

[0039] III. Immerse the entire mold in a silica gel solution, take it out and dry it to remove the n-hexane, and repeat the operation 1-5 times; demould after curing to obtain the overall structure of the sewing ring, the covering film and the support ring;

[0040] IV. Suture the suture ring to one end of the artificial blood vessel body in step I to prepare a complete blood vessel.

[0041] Compared with the prior art, the present invention is beneficial in that: the present invention provides an artificial blood vessel with a special structure, which utilizes the synergistic effect of the suture ring, the covering film and the support ring, not only improving the support effect on the anastomosis, but also solving the problem of anastomotic stenosis caused by scar hyperplasia at the suture mouth due to the existing suture method by isolating the contact between the suture mouth and the needle eye. The entire artificial blood vessel only needs one suture operation, and there is no need to worry about the problem of obvious anastomotic stenosis, avoiding subsequent secondary operations, and reducing the physiological, psychological and economic burdens of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 A cross-sectional view of an artificial blood vessel provided in a specific embodiment;

[0043] Figure 2 A cross-sectional view of an artificial blood vessel and a biological blood vessel provided in a specific embodiment after surgical suturing is completed;

[0044] Figure 3 A cross-sectional view of an artificial blood vessel and a biological blood vessel provided in a specific embodiment after surgical suturing is completed; in this figure, the end of the artificial blood vessel is protruding relative to the suturing ring;

[0045] Figure 4 It is a schematic diagram of an artificial blood vessel being sutured with a biological blood vessel at an inclined angle θ (eg, 45°);

[0046] Figure 5 This is a test photo of the test product 1 and the test product 2 connected in series through a hose in the test example.

[0047] In the figure: 1. artificial blood vessel body; 2. suture ring; 3. covering membrane; 4. support ring; 5. inner layer; 6. elastic dense layer; 7. outer layer; 8. suture layer. DETAILED DESCRIPTION

[0048] The technical solution of the present invention will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0049] The artificial blood vessels used in the following specific embodiments are as follows: Figure 1 , 2As shown, its structure includes an artificial blood vessel body 1, a suture ring 2, a covering film 3 and a supporting ring 4; the covering film 3 is a cylindrical structure, one end of the covering film 3 is connected to the end of the artificial blood vessel body 1, and the other end is provided with the supporting ring 4; the suture ring 2 is located at the end of the artificial blood vessel body 1, and the covering film 3 is located inside the suture ring 2; the outer diameter of the supporting ring 4 is at least 1.05 times (i.e. slightly larger than) the inner diameter of the artificial blood vessel body; the covering film is made of a flexible elastic material.

[0050] The artificial blood vessel bodies used in the following specific embodiments can be prepared by conventional preparation methods. Unless drugs that reduce vascular anastomotic stenosis are used, selecting common artificial blood vessel products on the market as the artificial blood vessel bodies will not have a significant impact on anastomotic stenosis.

[0051] For the sake of comparison, the artificial blood vessel body used in the following specific implementation manner is composed of an inner layer 5 , an elastic dense layer 6 and an outer layer 7 .

[0052] In some implementation cases, a suture layer is further provided on the outside of the suture ring, and the suture layer is composed of at least one material selected from the group consisting of polyurethane, expanded polytetrafluoroethylene, silicone rubber, and polyolefin.

[0053] In the following specific embodiments, the suture layers are all made of polyurethane.

[0054] In some other implementation cases, the surface of the suture ring and / or the support ring is also coated with a silicone layer and / or an anti-coagulation layer.

[0055] Generally, the silicone layer and the anticoagulant layer can be coated by conventional methods in the field of artificial blood vessels.

[0056] Furthermore, taking the coating of the silicone layer as an example, the coating method is as follows: (1) dispersing and dissolving medical-grade liquid silicone in one or more mixed solvents of acetic acid and saturated alkanes to prepare a 30-60% wt solution; (2) repeatedly immersing the suture ring and / or the support ring in the medical silicone solution in step (1) for 1-3 times, and drying to remove the solvent to form a dense and uniform silicone layer.

[0057] Specifically, in the following specific embodiments, the method for coating the silicone layer is: (1) dispersing and dissolving medical-grade liquid silicone in acetic acid (analytical grade) solvent to prepare a 50% wt solution; (2) repeatedly immersing the suture ring and / or support ring in the medical silicone solution in step (1) for 3 times, drying and removing the solvent to form a dense and uniform silicone layer.

[0058] In some embodiments, the surface of the covering film is also loaded with a functional coating, and the functional coating is composed of at least one of polyethyleneimine, phosphorylcholine, dextran sulfate, and heparin sodium.

[0059] In some implementation cases, taking sodium heparin as an example, the coating method is as follows: (1) dissolving polyethyleneimine in anhydrous ethanol to prepare a solution; (2) immersing the coating surface to be coated in the polyethyleneimine-ethanol solution for a period of time (e.g., 10-30 minutes); (3) immersing the coating surface in step (2) in a sodium heparin aqueous solution and bathing it in a 37° C. water bath for a period of time (e.g., 10-30 minutes); replacing the sodium heparin aqueous solution, repeating the water bath 1-3 times, and completing the coating after drying.

[0060] Furthermore, in the following specific embodiments, the method for coating the functional coating is: (1) dissolving polyethyleneimine (molecular weight 10,000) in anhydrous ethanol to prepare a 5 wt% solution; (2) immersing the coating surface to be coated in the polyethyleneimine-ethanol solution for 25 minutes; (3) immersing the coating surface in step (2) in a 3 wt% sodium heparin aqueous solution (pH = 1.0) in a 37°C water bath for 20 minutes; replacing the sodium heparin aqueous solution, repeating the water bath 3 times, and completing the coating after drying.

[0061] In some implementation cases, the length of the covering film is 2-4 times the thickness of the sewing ring.

[0062] In some implementation cases, the width of the sewing ring is 1-3 times the total wall thickness of the artificial blood vessel body.

[0063] In some implementation cases, the ring width of the support ring does not exceed 0.8 times the total wall thickness of the artificial blood vessel body, and is generally 0.5-0.8 times.

[0064] In the following specific implementation manner, the inner diameter of the artificial blood vessel body is 6 mm, the outer diameter is 8 mm, and the wall thickness is 1 mm.

[0065] Optionally, the suture ring and the support ring are made of at least one material selected from the group consisting of polyurethane, memory metal, polytetrafluoroethylene, silicone rubber, and polyolefin.

[0066] In the following specific embodiments, the suture ring and the support ring are both made of medical polyurethane.

[0067] Optionally, the covering film is composed of at least one of polyurethane, silicone rubber, expanded polytetrafluoroethylene, and polyolefin.

[0068] In the following specific implementation manner, the covering film is made of medical silicone.

[0069] In some implementation cases, the first method for preparing the artificial blood vessel is:

[0070] P1. preparing the inner layer of the artificial blood vessel;

[0071] P2. Sleeve the inner layer on the mold, sleeve the sewing ring at a predetermined position of the inner layer, and sleeve the support ring at a predetermined position of the mold; the support ring is arranged away from the inner layer;

[0072] P3. A layer of elastic dense layer is disposed on the outer surface of the inner layer, on the sewing ring and the support ring, and on the entire surface of the mold between the sewing ring and the support ring; the elastic dense layer formed between the support ring and the sewing ring is the covering film;

[0073] P4. An outer layer is arranged outside the elastic dense layer corresponding to the inner layer and the suture ring, and the mold is removed to obtain the artificial blood vessel.

[0074] Furthermore, in the following specific implementation manner, the first method for preparing the artificial blood vessel is:

[0075] (1) taking a spinning solution and forming the inner layer of the artificial blood vessel by electrospinning;

[0076] (2) The inner layer, the sewing ring and the support ring are placed on the rod column mold, the sewing ring is placed at the port on the outer surface of the inner layer, and the support ring is placed at a predetermined distance from the sewing ring;

[0077] (3) electrospray coating a silicone layer (i.e., an elastic dense layer) on the outer surface of the inner layer, the sewing ring and the support ring, and the portion between the sewing ring and the support ring;

[0078] The silicone layer completely wraps the sewing ring and the support ring, and forms a thin film (i.e., a covering film) to connect the sewing ring and the support ring together;

[0079] (4) The outer layer of the blood vessel is prepared by electrospinning on the outer surface of the dense layer, and the outer layer of the blood vessel covers the inner layer of the blood vessel and the suture ring.

[0080] Optionally, in the above steps (1) and (4), electrospinning may be performed using a method commonly used in the field of artificial blood vessels.

[0081] Specifically, in the following specific implementation manner, the electrospinning method of the above step (1) is as follows: first, PU (weight average molecular weight 200,000) is dissolved in a mixed solvent of N,N-dimethylformamide (DMF) and acetone (volume ratio of 1:1), heated in a 40°C water bath and stirred for 12 hours to obtain an electrospinning solution with a concentration of 18% (w / v); then, the above electrospinning solution is injected into a 20mL syringe, and connected to a stainless steel electrospinning spinneret through a polytetrafluoroethylene hose; then, the distance between the spinneret and the receiving rod is adjusted to 15cm, the ambient temperature of the spinning is 27°C, the ambient humidity is 25%RH, the voltage is adjusted to 30kV, the receiving rod speed is 100rad / min, the solution feeding rate is 1mL / h, and electrospinning is performed for 2 hours to obtain the inner layer structure of the artificial blood vessel.

[0082] Optionally, in the above step (3), the electrosprayed thickness of the elastic dense layer and the covering film is 0.2-0.5 times the total wall thickness of the artificial blood vessel body.

[0083] Specifically, in the following specific embodiments, the electrosprayed thickness of the elastic dense layer and the covering membrane is 0.5 times the total wall thickness of the artificial blood vessel body.

[0084] Optionally, in the above step (3), electrospraying may be performed using a method commonly used in the field of artificial blood vessels.

[0085] Specifically, in the following specific implementation, the electrospraying method of the above step (3) is as follows: the selected silicone elastomer is a single-component vulcanized liquid silicone with a molecular weight of 110,000-300,000; the solvent of the electrospray spinning solution is n-hexane, and the concentration of the silicone elastomer in the electrospray spinning solution is 35wt%. A 20ml syringe is connected to four stainless steel spinning nozzles respectively with a polytetrafluoroethylene hose, the spinning solution consumption rate of a single nozzle is 4ml / h, the voltage is 15kV, the receiving distance is 10cm, the spinning environment temperature is 30°C, the environmental humidity is 22%RH, the spinning time is 2h, and a dense silicone layer is formed.

[0086] Specifically, in the following specific implementation manner, the electrospinning method of the above step (4) is as follows: first, PU (weight average molecular weight 200,000) is dissolved in a mixed solvent of N,N-dimethylformamide (DMF) and acetone (volume ratio of 3:1), heated in a 40°C water bath and stirred for 12 hours to obtain an electrospinning solution with a concentration of 22% (w / v); then, the above electrospinning solution is injected into a 20 mL syringe and connected to a stainless steel electrospinning spinneret through a polytetrafluoroethylene hose; then, the distance between the spinneret and the receiving rod is adjusted to 20 cm; the spinning environment temperature is 30°C, the ambient humidity is 25% RH, the voltage is adjusted to 30 kV, the receiving rod speed is 100 rad / min, the solution feeding rate is 1 mL / h, and electrospinning is performed for 1 hour to obtain the electrospinning outer layer structure of the composite blood vessel.

[0087] In some other implementation cases, the second method for preparing the artificial blood vessel is:

[0088] Q1. The sewing ring, the covering film and the supporting ring are prepared as a whole, wherein the covering film is located between the sewing ring and the supporting ring;

[0089] Q2. Suture the suture ring to one end of the artificial blood vessel body, and set the covering film and the support ring away from the artificial blood vessel body to obtain the artificial blood vessel.

[0090] Furthermore, in the following specific implementation manner, the second method for preparing the artificial blood vessel is:

[0091] Ⅰ. Taking the spinning solution and preparing the artificial blood vessel inner layer, elastic dense layer and outer layer (i.e. the artificial blood vessel body) by electrospinning;

[0092] II. Prepare a silica gel solution, fix the sewing ring and the support ring at the predetermined position on the appropriate rod column mold to form the mold as a whole;

[0093] III. Immerse the entire mold in a silica gel solution, take it out and dry it to remove the n-hexane, and repeat the operation 1-5 times; demould after curing to obtain the overall structure of the sewing ring, the covering film and the support ring;

[0094] IV. Suture the suture ring to one end of the artificial blood vessel body in step I to prepare a complete blood vessel.

[0095] Optionally, in the above step I, the artificial blood vessel body can be prepared by electrospinning using a method commonly used in the field of artificial blood vessels.

[0096] Specifically, in the following specific implementation, the method for preparing the inner layer of the artificial blood vessel in the above step I is: the selected silicone elastomer is a single-component vulcanized liquid silicone with a molecular weight of 200,000; the solvent of the electrospinning solution is n-hexane, and the concentration of the silicone elastomer in the electrospinning solution is 35wt%. The receiving distance (the straight-line distance between the nozzle and the receiving rod) is 15cm, the solution consumption rate of a single spinning nozzle is 2ml / h, the number of spinning nozzles is 4, the voltage is 20kV, the spinning environment temperature is 30°C, and the ambient humidity is 40%. Electrospinning is performed for 2h to form a uniform white inner layer of the blood vessel.

[0097] The method for preparing the elastic dense layer in the above step I is: 4 spinning nozzles, a single nozzle spinning solution consumption rate of 4ml / h, a voltage of 15kV, a receiving distance of 10cm, a spinning time of 0.2h, forming a pre-treated silica gel dense layer structure; a large amount of silica gel solution is accumulated on the white inner layer of the electrospun silica gel, and the solvent has no time to evaporate to form a dense structure. The above sample is leached twice in a 30%wt silica gel-n-hexane solution, each leaching time is 10s, and a complete artificial blood vessel silica gel dense layer is obtained.

[0098] The method for preparing the outer layer of the artificial blood vessel in the above step I is as follows: the selected silicone elastomer is a single-component vulcanized liquid silicone with a molecular weight of 200,000; the solvent of the electrospinning solution is n-hexane, and the concentration of the silicone elastomer is 35%wt. The receiving distance (the straight-line distance between the nozzle and the receiving rod) is 15cm, the solution consumption rate of a single spinning nozzle is 2ml / h, the number of spinning nozzles is 4, the voltage is 20kV, the spinning environment temperature is 30°C, and the ambient humidity is 40%. Electrospinning is performed for 1h to form a uniform white outer layer of the blood vessel.

[0099] Optionally, in the above step III, the electrosprayed thickness of the elastic dense layer and the covering film is 0.2-0.5 times the total wall thickness of the artificial blood vessel body.

[0100] Specifically, in the following specific embodiments, the electrosprayed thickness of the elastic dense layer and the covering membrane is 0.5 times the total wall thickness of the artificial blood vessel body.

[0101] Optionally, the above step III is: immerse the entire mold in a silica gel / n-hexane solution (silica gel mass fraction 30-60%) for 10 seconds, take it out and dry it vertically for 30 minutes to remove the n-hexane, repeat the above operation 1-5 times, and demold after curing to obtain the overall structure of the sewing ring, covering film and support ring.

[0102] Specifically, in the following specific implementation manner, in the above step III, the silica gel mass fraction of the silica gel / n-hexane solution is 50%; the above operation is repeated 3 times.

[0103] Optionally, in the above step IV, the suture ring and the artificial blood vessel body are sutured together using a suturing method commonly used in surgery.

[0104] Specifically, in the following specific implementation manner, the suturing method in the above step IV is specifically: using 7-0 prolene suture thread, adopting the continuous suturing method to perform port anastomosis between the artificial blood vessel body and the suture ring.

[0105] Optionally, the end of the artificial blood vessel is arranged to protrude relative to the sewing ring (eg Figure 3 The protruding length is 0.5-1.5 times of the total wall thickness of the artificial blood vessel. In order to achieve a better suturing effect between the artificial blood vessel and the blood vessel of the organism, the protruding part of the end of the artificial blood vessel is inserted deep into the anastomosis. The protruding length of the protruding part varies with the total wall thickness of the artificial blood vessel. It should not be too long to affect blood flow, nor too short to have no effect.

[0106] Optionally, the artificial blood vessel provided by the present invention can also be sutured with the blood vessel of the organism at a certain tilt angle θ (such as 45°, 60°, etc.), as is commonly used in the industry. Figure 4 As shown, when sutured in an inclined manner, the anastomosis is shaped like an ellipse. In order to ensure the suture effect, the suture ring fits the anastomosis, so it is also shaped like an ellipse. The plane where the support ring is located must also maintain an approximately perpendicular relationship with the axial direction of the artificial blood vessel. In order to achieve this perpendicular relationship between the support rings, the port where the covering film is connected to the main part of the artificial blood vessel must be elliptical, and one side of the covering film is longer and the other side is shorter. If the length of the longer side is L and the length of the shorter side is l, the requirement for the length of the covering film in the present invention generally refers to the shorter length l, and it must satisfy Δl=(Ll)=D / tanθ, where D is the inner diameter (diameter) of the artificial blood vessel.

[0107] Example 1

[0108] In the artificial blood vessel provided in this embodiment, the main body of the artificial blood vessel is prepared by the first preparation method. The inner diameter (diameter) of the main body of the artificial blood vessel is 6 mm, the outer diameter (diameter) is 8 mm, and the total wall thickness is 1 mm. The width and thickness of the suture ring are both 1 mm, the length of the covering film is 4 mm, and the width of the support ring is 0.8 mm. That is: the length of the covering film is 4 times the thickness of the suture ring; the width of the suture ring is 1 times the total wall thickness of the artificial blood vessel, and the width of the support ring is 0.8 times the total wall thickness of the artificial blood vessel.

[0109] Example 2

[0110] The artificial blood vessel provided in this embodiment is prepared by the first preparation method. Similar to Example 1, the inner diameter of the artificial blood vessel body of this embodiment is 6 mm, the outer diameter is 8 mm, the total wall thickness is 1 mm, and the width of the suture ring is 3 mm and the thickness is 1 mm.

[0111] The length of the covering film is 2 mm, and the width of the supporting ring is 1 mm, that is, the length of the covering film is twice the thickness of the suture ring; the width of the supporting ring is 1 times the total wall thickness of the artificial blood vessel.

[0112] Example 3

[0113] The artificial blood vessel provided in this embodiment is prepared by the second preparation method; the sizes of the artificial blood vessel body, suture ring, covering film and support ring of this embodiment are the same as those of Example 1.

[0114] Example 4

[0115] The artificial blood vessel provided in this embodiment is prepared by the second preparation method; the sizes of the artificial blood vessel body, suture ring, covering film and support ring of this embodiment are the same as those of Example 2.

[0116] Test Example: Verification test of the problem of anastomotic stenosis of the segmental blood vessels prepared by using the artificial blood vessels of Examples 1-4

[0117] This test example selected the artificial blood vessels of Example 1 and Example 3 as test objects, and selected conventional artificial blood vessels with an inner diameter of 6 mm and an outer diameter of 8 mm to simulate biological blood vessels; and used two suturing methods to conduct the test.

[0118] Suturing method 1: Use 7-0 prolene suture and continuous suture method to anastomose two conventional artificial blood vessels to obtain test product 1.

[0119] Suturing method 2: Align the end of the artificial blood vessel with the anastomosis, and the support ring and the covering film enter the biological blood vessel from the anastomosis. Use 7-0 prolene sutures and a continuous suture method to first anastomose the ports of the artificial blood vessel prepared in Example 1 / Example 3 with the conventional artificial blood vessel, and place the support ring and the covering film inside the artificial blood vessel; then pull the support ring inside the artificial blood vessel to guide the support ring and the covering film into the artificial blood vessel, so that the support ring fits and supports the inner wall of the artificial blood vessel, and the covering film fits on the inner wall of the artificial blood vessel, and the covering film completely covers the suture needle hole and the suture thread, to obtain Test Product 2. The suture method of Test Product 2 is as follows: Figure 2 Or as shown in 3.

[0120] In the above-mentioned second suturing method, the support ring can be set in a commonly used surgical operation. For example, an endoscope can be used to extend forceps into the artificial blood vessel to clamp the support ring and pull it back; or, a guide wire can be set on the support ring in advance, and the guide wire can be set by pre-embedding the support ring; then pull the guide wire from the artificial blood vessel to pull the support ring and the covering film back into the artificial blood vessel. Regardless of the surgical method used, as long as the support ring and the covering film can be reintroduced into the artificial blood vessel, the plane of the support ring is perpendicular to the axis of the artificial blood vessel and can fit and support the inner wall of the artificial blood vessel, and the covering film fits the inner wall of the artificial blood vessel, it will be fine. From Figure 2 Or 3 can be seen that by suturing in this way, the sutures, stitches and vascular incisions in the artificial blood vessels are isolated by the covering film and will not come into direct contact with the blood, thereby reducing the risk of anastomotic stenosis after surgery.

[0121] Connect test product 1 and test product 2 in series through a hose and connect a peristaltic pump to form a test device. The connection method is as follows: Figure 4 shown.

[0122] The peristaltic pump flow rate was set at 820 ml / min, and the aqueous solution leaking from the sutures of test samples 1 and 2 was collected. The leakage amounts of the two test samples were compared using the gravimetric method.

[0123] The results showed that when the peristaltic pump was running for 1 minute, the leakage of Test 1 was 7 g, and the leakage of the artificial blood vessels prepared in Example 1 and Example 3 in Test 2 was 0 g. This indicates that the presence of the covering film significantly isolates the contact between the fluid and the suture, thereby greatly reducing the scar hyperplasia at the suture site and the occurrence of anastomotic stenosis.

[0124] The above specific embodiments describe the implementation of the present invention in detail, but the present invention is not limited to the specific details in the above embodiments. Within the scope of the claims and technical concept of the present invention, the technical solution of the present invention can be modified and changed in many simple ways, and these simple modifications all belong to the protection scope of the present invention.

Claims

1. An artificial blood vessel for reducing stenosis of vascular anastomosis, characterized in that: It includes an artificial blood vessel body, a suture ring, a covering film and a support ring; the covering film is a cylindrical structure, one end of the covering film is connected to the end of the artificial blood vessel body, and the other end is provided with the support ring; the suture ring is located at the end of the artificial blood vessel body, and the covering film is located inside the suture ring; the outer diameter of the support ring is not less than the inner diameter of the artificial blood vessel body; the covering film is made of flexible elastic material; the ring width of the support ring does not exceed 0.8 times the total wall thickness of the artificial blood vessel body.

2. The artificial blood vessel for reducing stenosis of vascular anastomosis according to claim 1, characterized in that: The length of the covering film is 2-4 times the thickness of the sewing ring.

3. The artificial blood vessel for reducing stenosis of vascular anastomosis according to claim 2, characterized in that: When the artificial blood vessel is sutured to the anastomosis at an inclined angle θ, the difference between the long side L and the short side l of the covering film is Δl, and Δl=D / tanθ, where D is the inner diameter of the artificial blood vessel.

4. The artificial blood vessel for reducing stenosis of vascular anastomosis according to claim 1, characterized in that: The ring width of the sewing ring is 1-3 times the total wall thickness of the artificial blood vessel body.

5. The artificial blood vessel for reducing stenosis of vascular anastomosis according to claim 1, characterized in that: A suture layer is also provided on the outside of the suture ring, and the suture layer is made of at least one material selected from the group consisting of polyurethane, expanded polytetrafluoroethylene, silicone rubber, and polyolefin.

6. The artificial blood vessel for reducing stenosis of vascular anastomosis according to claim 1, characterized in that: The surface of the sewing ring and / or the supporting ring is also provided with a silica gel layer and / or an anti-coagulation layer.

7. The artificial blood vessel for reducing stenosis of vascular anastomosis according to claim 1, characterized in that: The exterior of the covering film is loaded with a functional coating, which is composed of at least one of polyethyleneimine, phosphorylcholine, dextran sulfate, and heparin sodium.

8. The artificial blood vessel for reducing stenosis of vascular anastomosis according to claim 1, characterized in that: The end of the artificial blood vessel is arranged to protrude relative to the sewing ring, and the protruding length is 0.5-1.5 times the total wall thickness of the artificial blood vessel.

9. The method for preparing an artificial blood vessel for reducing stenosis of vascular anastomosis according to any one of claims 1 to 4, characterized in that: It is implemented by any of the following two methods; the first method includes the following steps: P1. preparing the inner layer of the artificial blood vessel; P2. Sleeve the inner layer, the sewing ring and the support ring on the mold, sleeve the sewing ring at a predetermined position of the inner layer, and sleeve the support ring at a predetermined position of the mold; the support ring is arranged away from the inner layer; P3. A layer of elastic dense layer is disposed on the outer surface of the inner layer, on the sewing ring and the support ring, and on the entire surface of the mold between the sewing ring and the support ring; the elastic dense layer formed between the support ring and the sewing ring is the covering film; P4, disposing an outer layer outside the elastic dense layer corresponding to the inner layer and the suture ring, demoulding, and obtaining the artificial blood vessel; Alternatively, the second method includes the following steps: Q1. The sewing ring, the covering film and the supporting ring are prepared as a whole, wherein the covering film is located between the sewing ring and the supporting ring; Q2. Suture the suture ring to one end of the artificial blood vessel body, and set the covering film and the support ring away from the artificial blood vessel body to obtain the artificial blood vessel.

Images