Self-adaptive valve skirt and preparation method thereof

Abstract

The invention discloses a self-adaptive valve skirt and a preparation method thereof, and particularly relates to the technical field of valves. The self-adaptive valve skirt comprises an upper-layer semi-permeable membrane, a lower-layer semi-permeable membrane, a water-soluble adhesive and inorganic salt, the upper-layer semi-permeable membrane and the lower-layer semi-permeable membrane are sealed to form a membrane bag for embedding a water-soluble adhesive and inorganic salt; the outer sides of the upper-layer semi-permeable membrane and the lower-layer semi-permeable membrane are coated with degradable coatings for sealing pores. The self-adaptive valve skirt has the self-adaptability of liquid, a gap between the valve and autologous tissue is well filled, and free flowing of the liquid does not generate pressure on a contact part, so that conduction block is not influenced.

Description

Technical Field

[0001] The present application relates to the field of valve technology, and in particular to an adaptive valve skirt and a preparation method thereof. Background Art

[0002] Post-TAVR regurgitation is one of the important complications that affect the effect of surgery, and its incidence and causes are related to multiple factors. Post-operative regurgitation mainly includes two types: paravalvular leakage and central regurgitation, of which paravalvular leakage is more common. According to clinical research data, the incidence of mild regurgitation after TAVR is about 40%, while the proportion of moderate to severe regurgitation is about 2%-10%. With the application of a new generation of valves and improvements in surgical techniques, the incidence of moderate to severe regurgitation has dropped significantly to below 5%. It is worth noting that there are differences in the incidence of regurgitation among different valve types. The incidence of early paravalvular leakage of self-expandable valves is relatively high, while the risk of central regurgitation of balloon-expandable valves is more prominent.

[0003] Surgical factors play a decisive role in the development of regurgitation. Improper valve size selection is the most common cause. Choosing a valve that is too small can lead to poor fit, while a valve that is too large can cause conduction block or annular damage. Implantation depth is also a significant factor. Too deep an implant can affect leaflet function, while too shallow an implant can lead to valve instability.

[0004] In transcatheter valve systems, paravalvular leakage is prevented by a skirt that physically coats the inner and outer sides of the stent. Common commercially available skirts include animal-derived pericardial tissue, fabrics (woven and knitted), and films. However, postoperative regurgitation rates are currently high, reaching approximately 40%, with moderate to severe regurgitation rates as high as 2%-10%.

[0005] Therefore, improvements in skirt materials and structures are a hot research topic for major device and pharmaceutical manufacturers. For example, Chinese invention patent application No. 2020106514860 discloses a composite skirt for a prosthetic heart valve. This skirt design utilizes materials of varying thickness, permeability, or functionality in different regions to adapt to native tissue, thereby reducing reflux and preventing thrombosis. However, this skirt is complex to manufacture, requiring additional suturing or bonding to effectively connect the materials in different regions, which undoubtedly increases manufacturing difficulty and the risk of leakage. Another example is Chinese invention patent application No. 2023116262766, which discloses a suture-free polymer heart valve skirt and its preparation method. This suture-free heart valve skirt is created by placing a heart valve stent into a polymer solution (polyurethane). While this heart valve skirt eliminates the need for additional fixing to the stent, saving manufacturing time, the gap between the skirt and the native tissue during use still presents a risk of reflux.

[0006] Therefore, designing a skirt that can fill the gap between the valve and the autologous tissue and is easy to connect to the stent is a difficult problem that needs to be solved urgently. Summary of the Invention

[0007] The present invention provides an adaptive valve skirt and a preparation method thereof. The adaptive valve skirt has liquid adaptability and can well fill the gap between the valve and autologous tissue. The free flow of liquid will not generate pressure on the contact parts, thereby affecting conduction block.

[0008] The object of the present invention is achieved through the following technical solutions: An adaptive valve skirt comprises an upper semipermeable membrane, a lower semipermeable membrane, a water-soluble adhesive and an inorganic salt; the upper and lower semipermeable membranes are sealed to form a membrane bag for embedding the water-soluble adhesive and the inorganic salt; the outer sides of the upper and lower semipermeable membranes are coated with a degradable coating with closed pores.

[0009] The two layers of semipermeable membrane are bonded together using a water-soluble adhesive, which reduces the free space in the membrane bag during the release and recovery process, thus reducing the recycling problems caused by the free space. Furthermore, the water-soluble adhesive dissolves after the membrane bag absorbs water, ensuring the normal function of the membrane bag.

[0010] The surface of the semipermeable membrane bag is coated with a degradable coating, which seals the pores of the semipermeable membrane. Before the coating degrades, there is no water in the semipermeable membrane bag, which presents a flat membrane state, which can effectively reduce the loading size and will not affect the release and recovery. After release, the coating is effectively degraded and the function of the membrane bag is restored. Under the action of the osmotic pressure of inorganic salts, the membrane bag absorbs water and expands. The expanded membrane bag has the same adaptability as liquid, which can fill the gap well and reduce paravalvular leakage.

[0011] Preferably, the water-soluble adhesive is selected from at least one of polyvinyl alcohol, polyacrylate emulsion, polyvinyl pyrrolidone, carboxymethyl cellulose, casein glue, and starch hydrolyzed glue.

[0012] Preferably, the inorganic salt is potassium salt, sodium salt or a combination of multiple inorganic salts. The inorganic salt is selected from at least one of sodium chloride, sodium sulfate, sodium carbonate and potassium chloride, potassium carbonate and potassium sulfate.

[0013] Preferably, the inorganic salt is sodium chloride, and the amount used is 0.05 mmol-2.40 mmol.

[0014] Preferably, the mass percentage of the inorganic salt in the water-soluble adhesive is 0.10%-0.30%.

[0015] Preferably, the degradable coating is selected from at least one of polyhydroxyalkanoates, polylactic acid and its copolymers, chitosan-nanocellulose, and polyacrylic acid (PAA) derivatives. The coating is degradable in blood, with a degradation time of 0.5-3 hours. The coating seals the pores of the semipermeable membrane prior to release, maintaining a flat membrane-like state and reducing loading size.

[0016] Preferably, both the upper and lower semipermeable membranes are RO membranes. The thickness of a single layer of RO membrane is 40-120 microns. The permeability of the RO membrane is limited by the size of the membrane bag and the amount of inorganic salts used. To reflect the controllability of the inorganic salts, the membrane bag volume is usually in a surplus state of 0.2-10 cubic centimeters. Preferably, the thickness of the film bag is 80-300 microns.

[0017] Preferably, one side of the semipermeable membrane bag is connected to the stent, and the connection method is selected from any one of gluing and suture.

[0018] Preferably, the expanded volume of the membrane bag is 0.2-10 cubic centimeters.

[0019] The present invention also provides a method for preparing an adaptive valve skirt, which comprises the following steps: S01. Preparation of skirt material: Use RO membrane and cut it into rectangular membrane sheets; S02. Preparation of coating solution: dissolving polylactic acid with a molecular weight of 4000-8000 in a mixed solution of ethylene dichloride and ethyl acetate, and stirring until completely dissolved to obtain a coating solution; S03, preparation of coating: taking the coating solution and evenly coating it on the surface of the RO membrane, and drying it naturally to obtain a skirt material coated with the coating solution; S04. Preparation of water-soluble glue: Weigh a preset amount of polyvinyl alcohol, starch hydrolyzed gelatin, and NaCl, dissolve them in water, raise the temperature to 50° C., and stir until fully dissolved to obtain water-soluble glue; S05. Evenly apply water-soluble glue on the rough surface of the skirt material, and place another rectangular film sheet with the smooth side facing up and the rough side facing the glue on the rectangular film sheet coated with water-soluble glue. Align the edges, and place the film bag in a 35-40°C oven for 2.5-3.5 hours to obtain an adaptive valve skirt.

[0020] Preferably, in step S01 , the rectangular diaphragm has a length of 91 mm and a width of 10 mm, and there are two rectangular diaphragms.

[0021] Preferably, in step S02, the mass ratio of dichloroethane to ethyl acetate is 4:1.

[0022] Preferably, in step S03, the coating times are 6 times.

[0023] Preferably, in step S05, the oven temperature is 37° C. and the baking time is 3 hours.

[0024] Preferably, in step S05 , a blank area of ​​1 mm not coated with water-soluble glue is left at the edge of the rectangular film.

[0025] Compared with the prior art, the advantages or beneficial effects of the technical solution of this application include: 1. One side of the semipermeable membrane bag is connected to the stent, with methods including gluing and sutures. The other side is a free end located on the outer surface of the stent. This connection to the stent limits water from expanding inwards, preventing it from affecting the opening and closing of the valve or the opening area. Furthermore, the edge of the semipermeable membrane is a free end with a width of 0.1-2 mm. The free end and free surface provide space for the skirt to expand, filling the gap between the valve and the native structure, thereby reducing the risk of paravalvular leakage.

[0026] 2. The change of environment causes the change of skirt function. For example, when the air environment becomes a blood environment, the selective permeability function of the semipermeable membrane bag can be turned on to avoid the qualitative change of the inside of the membrane bag in the air environment. The specificity of the use environment selection is high.

[0027] 3. By adding a water-soluble adhesive to the membrane bag, the free movement of the membrane bag can be restricted before release, eliminating the difficulty of recovery caused by free movement of the membrane bag. After release, the membrane bag expands in volume and has the adaptive properties of liquid, effectively filling the gap between the valve and the autologous tissue. The free flow of liquid does not exert pressure on the contact area and affect conduction block.

[0028] 4. Medical staff can adjust the salt content according to the patient's own condition. Without increasing the loading volume, they can effectively adjust the adaptive volume and further reduce the possibility of conduction block. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is a structural diagram of the valve skirt; Figure 2 This is the surface morphology of the coating in the initial state in the embodiment; Figure 3 This is a surface morphology of the coating after the membrane bag is placed in the buffer solution for 60 minutes; Figure 4 This is a surface morphology of the coating after the membrane bag was placed in the buffer solution for 80 minutes in the embodiment. DETAILED DESCRIPTION

[0030] The following will describe the implementation methods of this application in detail with reference to the accompanying drawings and examples, so that the application can fully understand how technical means are used to solve technical problems and achieve corresponding technical effects, and implement them accordingly. The embodiments of this application and the various features therein can be combined with each other without conflict, and the resulting technical solutions are all within the scope of protection of this application.

[0031] It should be clear that the embodiments described below are only some of the embodiments of this application, rather than all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without making any creative work are within the scope of protection of this application.

[0032] Example 1: This example describes the adaptive valve skirt solution in detail: 1. Preparation of skirt material: Cutting of membrane: Use commercially available Dow RO membrane and cut it into 91mm*10mm rectangular membrane*2.

[0033] 2. Preparation of coating solution: Dissolve 1g of polylactic acid with a molecular weight of 4000-8000 in 10ml of a mixed solution of dichloroethane and ethyl acetate (20% dichloroethane).

[0034] 3. Preparation of coating: Take 1 ml of coating solution and apply it evenly on the surface of RO membrane, wait for it to dry naturally, and apply it back and forth 4 times.

[0035] 4. Coating water permeability test: Place the membrane on the reverse osmosis test device, apply a pressure of 0.5MPa, and collect the water passing through within 10 minutes. If water passes through, it is unqualified.

[0036] 5. Preparation of water-soluble glue: Dissolve 1g polyvinyl alcohol, 6g starch hydrolyzed glue, and 0.021g NaCl in 6ml water, raise the temperature to 50℃, and stir until fully dissolved.

[0037] 6. Film bag preparation: Apply the water-soluble glue prepared in step 2 evenly to the rough surface, leaving a 1mm margin around the edges. Place another rectangular film sheet, smooth side up and rough side facing the glue, over the glued sheet, aligning the edges. Place the film bag in a 37°C oven for 3 hours. Seal the edges of the film bag with a 1mm sealer. Verify the film bag's performance.

[0038] 7. Film bag performance test: Thickness, the test results using a thickness gauge showed 128-136 microns, with an average of 130 microns.

[0039] 8. Coating Degradation Rate Test: Prepare phosphate buffered saline (PBS, pH 7.4) and add bovine serum albumin (45g / L). Place the membrane bag in the buffer solution and remove it every 20 minutes to inspect the surface morphology, water permeability, and weight gain. The results are shown in Table 1. The results show that the initial thickness of the membrane bag is approximately 130 microns, which is much thinner than the currently used pericardial membrane (200-300 microns). This allows for the use of smaller interventional devices during the loading process. From the microscopic image of the membrane bag surface ( Figure 2-Figure 4 ), polylactic acid is not completely degraded in the blood, but polylactic acid produces microcracks during the degradation process. These microcracks are sufficient to form water channels and support the recovery of RO membrane function.

[0040] Table 1 Statistical table of coating degradation rate results

[0041] Example 2: This example provides a solution for adaptive valve skirt that is different from Example 1. 1. Preparation of skirt material: Cutting of membrane: Use commercially available Dow RO membrane and cut it into 91mm*10mm rectangular membrane*2.

[0042] 2. Preparation of coating solution: Dissolve 1g chitosan powder in 100ml acetic acid solution and stir magnetically at 50°C until completely dissolved (approximately 2-4 hours). Adjust the pH to 4-6 (using a dilute NaOH solution). Disperse the nanocellulose in water (1% w / v) and sonicate for 20-30 minutes at 300W to prevent agglomeration. Slowly add the nanocellulose and dispersion to the chitosan solution (1:5 mass ratio) and sonicate for 20-30 minutes at 300W while stirring.

[0043] 3. Preparation of coating: Rotate the membrane at 1000-3000 rpm, apply 1 ml of coating solution evenly on the surface of RO membrane, wait for natural drying, and apply back and forth 12 times.

[0044] 4. Coating water permeability test: Place the membrane on the reverse osmosis test device, apply a pressure of 0.5MPa, and collect the water passing through within 10 minutes. If water passes through, it is unqualified.

[0045] 5. Preparation of water-soluble glue: Dissolve 1g polyvinyl alcohol, 6g starch, and 0.021g NaCl hydrolyzed glue in 6ml water, raise the temperature to 50℃, and stir until fully dissolved.

[0046] 6. Film bag preparation: Apply the water-soluble glue prepared in step 2 evenly to the rough surface, leaving a 1mm margin around the edges. Place another rectangular film sheet, smooth side up and rough side facing the glue, over the glued sheet, aligning the edges. Place the film bag in a 37°C oven for 3 hours. Seal the edges of the film bag with a 1mm sealer. Verify the film bag's performance.

[0047] 7. Film bag performance test: Thickness, the test results using a thickness gauge showed 135-142 microns, with an average of 138 microns.

[0048] 8. Test of coating degradation rate: Prepare phosphate buffer solution (PBS, pH 7.4) and add bovine serum albumin (45g / L). Place the membrane bag in the buffer solution and take it out every 20 minutes to check the water permeability and weight gain. The results are as follows: Figure 2 shown.

[0049] The difference between this example and Example 1 is that a different degradable coating is used. This degradable coating has a relatively faster hydrolysis rate, which can restore the use of the semipermeable membrane in a shorter time. The statistical results of the coating degradation rate of this example are shown in Table 2.

[0050] Table 2 Statistical results of coating degradation rate

[0051] Example 3: This example further explores the relationship between the content of inorganic salts and the water absorption of the film bag 1. Preparation of skirt material: Cutting of membrane: Use commercially available Dow RO membrane and cut it into 91mm*10mm rectangular membrane*2.

[0052] 2. Preparation of coating solution: Dissolve 1g of polylactic acid with a molecular weight of 4000-8000 in 10ml of a mixed solution of dichloroethane and ethyl acetate (20% dichloroethane).

[0053] 3. Preparation of coating: Take 1 ml of coating solution and apply it evenly on the surface of RO membrane, wait for it to dry naturally, and apply it back and forth 4 times.

[0054] 4. Coating water permeability test: Place the membrane on the reverse osmosis test device, apply a pressure of 0.5MPa, and collect the water passing through within 10 minutes. If water passes through, it is unqualified.

[0055] 5. Preparation of water-soluble glue: Dissolve 1g polyvinyl alcohol, 6g starch hydrolyzed glue, and 0.035g NaCl in 6ml water, raise the temperature to 50℃, and stir until fully dissolved.

[0056] 6. Film bag preparation: Apply the water-soluble glue prepared in step 2 evenly to the rough surface, leaving a 1mm margin around the edges. Place another rectangular film sheet, smooth side up and rough side facing the glue, over the glued sheet, aligning the edges. Place the film bag in a 37°C oven for 3 hours. Seal the edges of the film bag with a 1mm sealer. Verify the film bag's performance.

[0057] 7. Film bag performance test: Thickness, the test results using a thickness gauge showed 131-142 microns, with an average of 134 microns.

[0058] 8. Test of coating degradation rate: Prepare phosphate buffer solution (PBS, pH 7.4) and add bovine serum albumin (45g / L). Place the membrane bag in the buffer solution and take it out every 20 minutes to check the water permeability and weight gain. The results are as follows: Figure 3 shown.

[0059] By comparing Example 1 with this example, it can be found that by adjusting the content of inorganic salts, the water absorption of the membrane bag can be significantly increased, thereby adjusting the adaptive ability of the membrane bag. The statistical results of the coating degradation rate of this example are shown in Table 3.

[0060] Table 3 Statistical results of coating degradation rate

[0061] Example 4: Effect of coating thickness on usage 1. Preparation of skirt material: Cutting of membrane: Use commercially available Dow RO membrane and cut it into 91mm*10mm rectangular membrane*2.

[0062] 2. Preparation of coating solution: Dissolve 1g of polylactic acid with a molecular weight of 4000-8000 in 10ml of a mixed solution of dichloroethane and ethyl acetate (20% dichloroethane).

[0063] 3. Preparation of coating: Take 1 ml of coating solution and apply it evenly on the surface of RO membrane, wait for it to dry naturally, and apply it back and forth 6 times.

[0064] 4. Coating water permeability test: Place the membrane on the reverse osmosis test device, apply a pressure of 0.5MPa, and collect the water passing through within 10 minutes. If water passes through, it is unqualified.

[0065] 5. Preparation of water-soluble glue: Dissolve 1g polyvinyl alcohol, 6g starch hydrolyzed glue, and 0.021g NaCl in 6ml water, raise the temperature to 50℃, and stir until fully dissolved.

[0066] 6. Film bag preparation: Apply the water-soluble glue prepared in step 2 evenly to the rough surface, leaving a 1mm margin around the edges. Place another rectangular film sheet, smooth side up and rough side facing the glue, over the glued sheet, aligning the edges. Place the film bag in a 37°C oven for 3 hours. Seal the edges of the film bag with a 1mm sealer. Verify the film bag's performance.

[0067] 7. Film bag performance test: Thickness, the test results using a thickness gauge showed 140-153 microns, with an average of 146 microns.

[0068] 8. Test of coating degradation rate: Prepare phosphate buffer solution (PBS, pH 7.4) and add bovine serum albumin (45g / L). Place the membrane bag in the buffer solution and take it out every 20 minutes to check the water permeability and weight gain. The results are as follows: Figure 4 shown.

[0069] This example differs from Example 1 in that the degradable coating was applied more frequently to the RO membrane surface, increasing its thickness. This increase in overall thickness was also evident, increasing from 130 microns in Example 1 to 146 microns. The degradation time was also significantly increased, providing ample time for surgery. The final water absorption of the membrane bag was similar to that of Example 1, indicating that the thickness of the degradable coating had a limited effect on the final water absorption of the membrane bag. The statistical results of the coating degradation rate in this example are shown in Table 4.

[0070] Table 4 Statistical results of coating degradation rate

Claims

1. An adaptive valve skirt, characterized in that: It includes an upper semipermeable membrane, a lower semipermeable membrane, a water-soluble adhesive and an inorganic salt; The upper semipermeable membrane and the lower semipermeable membrane are sealed to form a membrane bag for embedding water-soluble adhesive and inorganic salt; The outer sides of the upper semipermeable membrane and the lower semipermeable membrane are both coated with a degradable coating with closed pores.

2. The adaptive valve skirt according to claim 1, characterized in that: The water-soluble adhesive is selected from at least one of polyvinyl alcohol, polyacrylate emulsion, polyvinyl pyrrolidone, carboxymethyl cellulose, casein glue, and starch hydrolyzed glue.

3. The adaptive valve skirt according to claim 1, characterized in that: The inorganic salt is selected from at least one of sodium chloride, sodium sulfate, sodium carbonate and potassium chloride, potassium carbonate and potassium sulfate.

4. The adaptive valve skirt according to claim 3, characterized in that: The inorganic salt is sodium chloride, and the amount used is 0.05mmol-2.40mmol.

5. The adaptive valve skirt according to claim 1, characterized in that: The inorganic salt content in the water-soluble adhesive is 0.10%-0.30%.

6. The adaptive valve skirt according to claim 1, characterized in that: The degradable coating is selected from at least one of polyhydroxyalkanoate, polylactic acid and its copolymer, chitosan-nanocellulose, and polyacrylic acid derivatives.

7. The adaptive valve skirt according to claim 1, characterized in that: The upper semipermeable membrane and the lower semipermeable membrane are both RO membranes.

8. The adaptive valve skirt according to claim 1, characterized in that: The thickness of the film bag is 80-300 microns.

9. The adaptive valve skirt according to claim 1, characterized in that: One side of the semipermeable membrane bag is connected to the stent, and the connection method is selected from any one of gluing and suture.

10. A method for preparing an adaptive valve skirt, characterized in that: The steps include: S01. Preparation of skirt material: Use RO membrane and cut it into rectangular membrane sheets; S02. Preparation of coating solution: dissolving polylactic acid with a molecular weight of 4000-8000 in a mixed solution of ethylene dichloride and ethyl acetate, and stirring until completely dissolved to obtain a coating solution; S03, preparation of coating: taking the coating solution and evenly coating it on the surface of the RO membrane, and drying it naturally to obtain a skirt material coated with the coating solution; S04. Preparation of water-soluble glue: Weigh a preset amount of polyvinyl alcohol, starch hydrolyzed gelatin, and NaCl, dissolve them in water, raise the temperature to 50° C., and stir until fully dissolved to obtain a water-soluble glue; S05. Evenly apply water-soluble glue on the rough surface of the skirt material, and place another rectangular film sheet with the smooth side facing up and the rough side facing the glue on the rectangular film sheet coated with water-soluble glue. Align the edges, and place the film bag in a 35-40°C oven for 2.5-3.5 hours to obtain an adaptive valve skirt.

Images