Degradation-speed-controllable closing device for closing opening of blood vessel wall

Abstract

The invention discloses a closing device with a controllable degradation speed for closing an opening of a blood vessel wall, which comprises an anchoring part, a degradable magnesium alloy, a degradable magnesium alloy, a degradable magnesium alloy, a degradable magnesium alloy and a degradable magnesium alloy, and is characterized in that the anchoring part is positioned in a blood vessel cavity when in use; the fixing piece is located outside the blood vessel wall when used, and the fixing piece is made of degradable collagen; the connecting piece penetrates through the blood vessel wall opening during use, and the connecting piece pulls the anchoring piece and the fixing piece to be close to each other so as to seal the blood vessel wall opening; the magnesium alloy is composed of magnesium, aluminum and copper, the magnesium alloy comprises the copper with the mass fraction being 0.01%-0.05% and the aluminum with the mass fraction being 1.0%-8.0%, and the degradation speed of the magnesium alloy in the blood environment is 0.7 mg / cm < 2 >. H to 1.3 mg / cm < 2 >. H. According to the closing device made of the magnesium alloy and used for closing the opening of the blood vessel wall, the components in the magnesium alloy are adjusted, and the expected degradation speed is obtained.

Description

Technical Field

[0001] The present application relates to the technical field of medical materials, and in particular to a closure device with controllable degradation rate for closing an opening in a blood vessel wall. Background Art

[0002] In the prior art, magnesium alloys are used in the field of medical material technology and can be degraded in a biological environment (such as in the blood). The degradation rate of magnesium alloys is related to the types and contents of the components other than magnesium in the magnesium alloys. When magnesium alloys are used as in vivo degradable materials, the types and contents of the components in the magnesium alloys need to be adjusted to achieve an optimal degradation rate, which is neither faster than the healing rate nor too slow, causing other adverse effects such as endothelialization. Summary of the invention

[0003] Based on this, a closure device made of magnesium alloy for sealing the opening of the blood vessel wall is provided, and the components in the magnesium alloy are adjusted to obtain the expected degradation rate.

[0004] A closure device for closing an opening in a blood vessel wall, comprising:

[0005] An anchoring piece, which is located in the blood vessel cavity when in use, and is made of a degradable magnesium alloy;

[0006] A fixing piece, which is located outside the blood vessel wall when in use, and the fixing piece is made of degradable collagen;

[0007] A connecting piece, which penetrates the blood vessel wall opening when in use, and pulls the anchoring piece and the fixing piece closer to each other to close the blood vessel wall opening;

[0008] The magnesium alloy is composed of magnesium, aluminum and copper. The magnesium alloy contains 0.01% to 0.05% copper by mass and 1.0% to 8.0% aluminum by mass. The degradation rate of the magnesium alloy in the blood environment is 0.7 to 1.3 mg / cm 2 ·h.

[0009] Optionally, the magnesium alloy is composed of magnesium, aluminum, copper and iron, wherein the magnesium alloy contains 0.01% to 0.05% copper by mass, 1.0% to 8.0% aluminum by mass, and 0.05% to 0.23% iron by mass, and the degradation rate of the magnesium alloy in the blood environment is 0.8 to 1.4 mg / cm 2 ·h.

[0010] Several optional methods are also provided below, but they are not intended to be additional limitations on the above-mentioned overall solution, but are merely further supplements or preferences. Under the premise that there are no technical or logical contradictions, each optional method can be combined with the above-mentioned overall solution separately, and multiple optional methods can also be combined.

[0011] Optionally, the magnesium alloy contains aluminum in an amount of 1.5%, 3.0%, 4.5%, 6.0% or 7.5% by mass.

[0012] Optionally, the magnesium alloy contains copper in an amount of 0.01%, 0.02%, 0.03%, 0.04% or 0.05% by mass.

[0013] Optionally, the magnesium alloy contains 1.5% by mass of aluminum and 0.01% by mass of copper.

[0014] Optionally, the magnesium alloy contains 3.0% by mass of aluminum and 0.02% by mass of copper.

[0015] Optionally, the magnesium alloy contains 4.5% by mass of aluminum and 0.03% by mass of copper.

[0016] Optionally, the magnesium alloy contains 6.0% by mass of aluminum and 0.04% by mass of copper.

[0017] Optionally, the magnesium alloy contains 7.5% by mass of aluminum and 0.05% by mass of copper.

[0018] Optionally, the magnesium alloy contains iron in an amount of 0.05%, 0.08%, 0.12%, 0.16%, 0.20% or 0.23% by mass.

[0019] Optionally, the magnesium alloy contains 1.5% by mass of aluminum, 0.01% by mass of copper, and 0.05% by mass of iron.

[0020] Optionally, the magnesium alloy contains 3.0% by mass of aluminum, 0.02% by mass of copper, and 0.08% by mass of iron.

[0021] Optionally, the magnesium alloy contains 4.5% by mass of aluminum, 0.03% by mass of copper, and 0.12% by mass of iron.

[0022] Optionally, the magnesium alloy contains 6.0% by mass of aluminum, 0.04% by mass of copper, and 0.16% by mass of iron.

[0023] Optionally, the magnesium alloy contains 7.5% by mass of aluminum, 0.05% by mass of copper, and 0.20% by mass of iron.

[0024] Optionally, the surface of the anchor is surface treated with a treatment liquid, wherein the treatment liquid comprises 5% to 10% by mass of acid and 0.4% to 0.8% by mass of ferrous sulfate.

[0025] Optionally, the treatment time of the treatment liquid does not exceed 5 minutes.

[0026] The present application provides a closure device made of magnesium alloy for sealing a blood vessel wall opening, wherein the components in the magnesium alloy are adjusted to obtain an expected degradation rate. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 A schematic diagram of a closure device for closing a blood vessel wall opening according to the present invention;

[0028] Figure 2 Schematic diagram of the effect of aluminum content and copper content of magnesium alloy on degradation rate in this application (in vitro simulated degradation experiment);

[0029] Figure 3 This is a photo of Example 1 before implantation into the femoral artery of a domestic pig;

[0030] Figure 4 This is a photo of Example 1 7 days after implantation into the femoral artery of a domestic pig. DETAILED DESCRIPTION

[0031] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0032] In order to better describe and illustrate the embodiments of the present application, reference may be made to one or more drawings, but the additional details or examples used to describe the drawings should not be considered as limiting the scope of the invention of the present application, any of the currently described embodiments or preferred methods.

[0033] It should be noted that when a component is referred to as being "connected" to another component, it may be directly connected to the other component or there may be a central component. When a component is referred to as being "disposed on" another component, it may be directly disposed on the other component or there may be a central component at the same time.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0035] See also Figure 1 As shown, a closure device for closing an opening in a blood vessel wall comprises:

[0036] The anchor 300 is located in the blood vessel cavity when in use, and the anchor 300 is made of a degradable magnesium alloy;

[0037] The fixing member 200 is located outside the blood vessel wall when in use, and the fixing member 200 is made of degradable collagen;

[0038] The connecting member 100, when in use, penetrates the opening of the blood vessel wall, and the connecting member 100 pulls the anchor member 300 and the fixing member 200 closer to each other to close the opening of the blood vessel wall 400;

[0039] Magnesium alloy is composed of magnesium, aluminum and copper. The magnesium alloy contains 0.01% to 0.05% copper and 1.0% to 8.0% aluminum by mass. The degradation rate of magnesium alloy in the blood environment is 0.7 to 1.3 mg / cm 2 ·h.

[0040] The anchor 300 and the fixing member 200 are respectively located on the inner and outer sides of the blood vessel wall 400. The anchor 300 and the fixing member 200 are connected and fixed by the connecting member 100. The anchor 300 and the fixing member 200 are clamped and fixed on the blood vessel wall, and block the opening on the blood vessel wall to prevent blood from flowing out of the blood vessel wall. Figure 1 The middle arrow indicates the direction of blood flow.

[0041] The anchor 300 and the fixing member 200 are both made of degradable materials, and the degradation periods of the three are different. The degradation time T1 of the anchor 300 is 7 to 14 days, and the degradation time T2 of the fixing member 200 is 60 to 90 days, and T2-T1≥45 days.

[0042] The anchoring member and the fixing member are automatically and completely degraded in the body, and no surgery is required. The connecting member can be a degradable or non-degradable suture.

[0043] The anchor is made of magnesium alloy, which is exposed in the blood vessel lumen and immersed in blood. The magnesium alloy material needs to have biocompatibility and an expected degradation rate to reduce damage to the organism and degrade within the expected time after the blood vessel stops bleeding.

[0044] The biocompatibility of magnesium is known to be safe, and the other added components and their dosages in magnesium alloys are also safe. The problem is that it is necessary to screen out the magnesium alloy material with the optimal degradation rate, which can cause the least rejection reaction and can be degraded in the shortest time after the blood vessel wall's own wound stops bleeding.

[0045] It is very costly to conduct direct in vivo testing on magnesium alloys. Instead, simulated degradation tests can be conducted in vitro to screen out the best solution, and then in vivo testing can be conducted.

[0046] In the present application, the in vitro degradation time of the magnesium alloy can be obtained by the following method.

[0047] In a 37±1℃ water bath, the weighed magnesium alloy sample was immersed in simulated body fluid (PBS) without stirring or shaking during the immersion process. After static immersion for several days, the magnesium alloy sample was taken out from the simulated body fluid, rinsed with purified water and then cleaned with ethanol, dried at room temperature and then weighed. The weight and test time were recorded, the degradation curve was drawn and the degradation time was calculated.

[0048] The effects of different component contents on the degradation rate of magnesium alloy samples are shown in Tables 1 and Figure 2 As shown, different addition amounts of aluminum and copper will improve the degradation rate of magnesium alloys.

[0049] Table 1

[0050]

[0051] The blood conditions, physiological structure and endothelial tissue of the femoral artery of a domestic pig are similar to those of a human femoral artery. The pathological tissue response of the implant is also similar to that of the human body, making it an ideal mimic of the human femoral artery. The magnesium alloy sample of Example 1 is implanted in the femoral artery of a domestic pig.

[0052] Before the in vivo test, the surface of the magnesium alloy is treated by soaking, spraying or directly applying the treatment solution to the magnesium alloy, then cleaning it in water and drying it. The treatment solution can usually be an acid solution, such as hydrochloric acid, sulfuric acid, nitric acid, acetic acid, oxalic acid, tartaric acid, etc. The acid concentration should not be too high, usually 1mg / L to 10000mg / L.

[0053] The treatment solution may also be added with an accelerator, which may be a soluble transition metal salt, such as a salt of iron, manganese, or cobalt. The concentration of the accelerator is generally 0.01 mg / mL to 1000 mg / mL.

[0054] The contact time between the treatment liquid and the magnesium alloy does not exceed 5 minutes, and the contact time can also control the degradation rate.

[0055] For example, the sample is chemically treated in an acidic solution of ferrous sulfate (sulfuric acid or acetic acid), 1g of 98% sulfuric acid H2S04 and 0.04g FeSO4 are added to 10mL of water to obtain a mixed solution, and the sample is immersed in the mixed solution for 2 minutes to enrich the surface of the sample with iron and transition metal impurities, thereby accelerating the degradation rate of the magnesium alloy. As shown in Table 2, after the sample is chemically treated in this way, the degradation rate increases.

[0056] See also Figure 3 As shown, the magnesium alloy of Example 1 was photographed before being implanted into the femoral artery of a domestic pig, see Figure 4 As shown, the magnesium alloy of Example 1 was implanted in the femoral artery of a domestic pig for 7 days. Figure 4 At the position indicated by the middle arrow, the magnesium alloy is completely degraded.

[0057] See also Figure 4 As shown in the figure, after 7 days, most of the magnesium alloy was degraded, and the degradation process was basically uniform, and there was no obvious endothelialization phenomenon on the surface of the magnesium alloy.

[0058] Table 2

[0059]

[0060] From the scanning electron micrograph image of the polished cross-section of the surface-treated magnesium alloy, it can be seen that the location where the impurity elements and transition metals are concentrated is the starting location of the degradation of the magnesium alloy. The starting location of the dispersed degradation of the magnesium alloy is very important for the degradation rate of the overall component. The image of the scanning electron micrograph shows that the active degradation sites of the magnesium alloy are well dispersed, which ultimately leads to a uniform degradation rate throughout the magnesium alloy.

[0061] When the magnesium alloy sample contains iron, the effect of different component contents on the degradation rate is shown in Table 3. Iron mainly occupies the position in the metal lattice, causing microscopic defects in the metal, which will accelerate the corrosion process. Different addition amounts of each component will improve the degradation rate of the magnesium alloy.

[0062] Table 3

[0063]

[0064]

[0065] After the samples were chemically treated with the treatment solution, the degradation rates were shown in Table 4.

[0066] Table 4

[0067]

[0068] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0069] The above-mentioned embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the attached claims.

Claims

1. A closure device with controllable degradation rate for closing an opening in a blood vessel wall, characterized in that: include: An anchoring piece, which is located in the blood vessel cavity when in use, and is made of a degradable magnesium alloy; A fixing piece, which is located outside the blood vessel wall when in use, and the fixing piece is made of degradable collagen; A connecting piece, which penetrates the blood vessel wall opening when in use, and pulls the anchoring piece and the fixing piece closer to each other to close the blood vessel wall opening; The magnesium alloy is composed of magnesium, aluminum and copper. The magnesium alloy contains 0.01% to 0.05% copper by mass and 1.0% to 8.0% aluminum by mass. The degradation rate of the magnesium alloy in the blood environment is 0.7 to 1.3 mg / cm 2 ·h.

2. The closure device with controllable degradation rate for sealing a blood vessel wall opening according to claim 1, characterized in that: The magnesium alloy contains aluminum in an amount of 1.5%, 3.0%, 4.5%, 6.0% or 7.5% by mass.

3. The closure device with controllable degradation rate for sealing a blood vessel wall opening according to claim 1, characterized in that: The magnesium alloy contains copper in an amount of 0.01%, 0.02%, 0.03%, 0.04% or 0.05% by mass.

4. The closure device with controllable degradation rate for sealing a blood vessel wall opening according to claim 1, characterized in that: The magnesium alloy contains 1.5% by mass of aluminum and 0.01% by mass of copper.

5. The closure device with controllable degradation rate for sealing a blood vessel wall opening according to claim 1, characterized in that: The magnesium alloy contains 3.0% by mass of aluminum and 0.02% by mass of copper.

6. The closure device with controllable degradation rate for sealing a blood vessel wall opening according to claim 1, characterized in that: The magnesium alloy contains 4.5% by mass of aluminum and 0.03% by mass of copper.

7. The closure device with controllable degradation rate for sealing a blood vessel wall opening according to claim 1, characterized in that: The magnesium alloy contains 6.0% by mass of aluminum and 0.04% by mass of copper.

8. The closure device with controllable degradation rate for sealing a blood vessel wall opening according to claim 1, characterized in that: The magnesium alloy contains 7.5% by mass of aluminum and 0.05% by mass of copper.

9. The closure device with controllable degradation rate for sealing a blood vessel wall opening according to any one of claims 1 to 8, characterized in that: The surface of the anchor is treated with a treatment liquid, wherein the treatment liquid comprises 5% to 10% by mass of acid and 0.4% to 0.8% by mass of ferrous sulfate.

10. The closure device with controllable degradation rate for sealing a blood vessel wall opening according to claim 9, characterized in that: The treatment time of the treatment solution does not exceed 5 minutes.

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