An adaptive valve skirt and method of making the same

Abstract

The application discloses a self-adapting valve skirt and a preparation method thereof, and particularly relates to the technical field of valves. The self-adapting valve skirt comprises an upper semi-permeable membrane, a lower semi-permeable membrane, a water-soluble adhesive and inorganic salt; the upper semi-permeable membrane and the lower semi-permeable membrane are sealed to form a membrane bag for embedding the water-soluble adhesive and the inorganic salt; and the outer sides of the upper semi-permeable membrane and the lower semi-permeable membrane are coated with a degradable coating layer for sealing pores. The self-adapting valve skirt has the self-adapting property of liquid, can well fill the gap between the valve and autologous tissue, and the free flow of liquid will not generate pressure on the contacted part, thereby affecting the conduction block.

Description

TECHNICAL FIELD

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

[0002] Post-TAVR regurgitation is one of the important complications affecting the effectiveness of the operation, and its incidence and causes are related to multiple factors. Postoperative regurgitation mainly includes 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 new generation of valves and the improvement of surgical techniques, the incidence of moderate to severe regurgitation has decreased significantly to below 5%. It is worth noting that different valve types differ in the incidence of regurgitation, and the early paravalvular leakage rate of self-expanding valves is relatively high, while the central regurgitation risk of balloon-expandable valves is more prominent.

[0003] Surgical operating factors play a decisive role in the occurrence of regurgitation. Improper valve size selection is the most common cause, and selecting a too small valve will lead to poor fit, while a too large valve may cause conduction block or valve ring damage. Improper implantation depth is also an important factor, and too deep implantation may affect valve leaflet function, while too shallow implantation may lead to unstable valve.

[0004] In the transcatheter valve system, the skirt physically covered on both sides of the stent plays a role in preventing paravalvular leakage. Common commercial skirts include animal-derived pericardial tissue, fabric (woven fabric, knitted fabric), and membrane materials. However, the current postoperative regurgitation rate is relatively high, with a regurgitation rate of about 40%, and a moderate to severe regurgitation rate of up to 2%-10%.

[0005] Therefore, the improvement of skirt materials and structures is a hot research direction for major medical device manufacturers. For example, Chinese invention patent application No. 2020106514860 discloses a composite skirt for artificial heart valve, in the design of which different regions select different thickness, permeability or functional materials to achieve adaptation to the native tissue, thereby reducing regurgitation, anti-thrombosis and other functions. However, the above-mentioned skirt is too complex to make, and the materials in different regions need to be additionally stitched or bonded to achieve effective connection, which undoubtedly increases the difficulty of making and the risk of leakage. For another example, Chinese invention patent application No. 2023116262766 discloses a suture-free high-molecular heart valve skirt and a preparation method thereof, which obtains a suture-free heart valve skirt by placing a heart valve stent in a high-molecular solution (polyurethane). Although the above-mentioned heart valve skirt does not need to be fixed with the stent, saving the production time, there is still a gap between the skirt and the autologous tissue when in use, which is still prone to regurgitation risk.

[0006] Therefore, designing a skirt which can fill the gap between the valve and the autologous tissue and is simple to connect with the stent is an urgent problem to be solved. SUMMARY

[0007] The application provides a self-adapting valve skirt and a preparation method thereof.

[0008] The application aims to achieve the above-mentioned technical problems by the following technical scheme.

[0009] The self-adapting valve skirt comprises an upper semi-permeable membrane, a lower semi-permeable membrane, a water-soluble adhesive and inorganic salt.

[0010] The two semi-permeable membranes are bonded into one layer by the water-soluble adhesive, so that the free space of the membrane bag in the releasing and recycling operation is reduced, and the recycling problem caused by the free space is reduced.

[0011] The semi-permeable membrane bag is coated with a degradable coating, the coating closes the pores of the semi-permeable membrane, and before the coating is degraded, the semi-permeable membrane bag is in a flat membrane state without water, so that the loading size can be effectively reduced and the releasing and recycling are not affected.

[0012] Preferably, the water-soluble adhesive is at least one of polyvinyl alcohol, polyacrylate emulsion, polyvinylpyrrolidone, carboxymethyl cellulose, casein glue and starch hydrolysis glue.

[0013] Preferably, the inorganic salt is potassium salt, sodium salt or a plurality of inorganic salts.

[0014] Preferably, the inorganic salt is sodium chloride, and the amount is 0.05mmol-2.40mmol.

[0015] Preferably, the mass percentage of the inorganic salt in the water-soluble adhesive is 0.10%-0.30%.

[0016] 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.

[0017] 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.

[0018] Preferably, the thickness of the film bag is 80-300 microns.

[0019] 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.

[0020] Preferably, the expanded volume of the membrane bag is 0.2-10 cubic centimeters.

[0021] The present invention also provides a method for preparing an adaptive valve skirt, which comprises the following steps:

[0022] S01. Preparation of skirt material: Use RO membrane and cut it into rectangular membrane sheets;

[0023] 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;

[0024] 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;

[0025] 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;

[0026] 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.

[0027] 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.

[0028] As preferred, in step S02, the mass ratio of dichloroethane and ethyl acetate is 4:1.

[0029] As preferred, in step S03, the coating times are 6 times.

[0030] As preferred, in step S05, the oven temperature is 37℃, and the baking time is 3h.

[0031] As preferred, in step S05, the rectangular film piece leaves a blank area of 1mm without water-soluble glue.

[0032] Compared with the prior art, the technical scheme of the present application has the advantages or beneficial effects including:

[0033] 1. One side of the semi-permeable membrane bag is connected with the support, and the connection mode is not limited to gluing, suturing, etc., and the other side is a free end and is located on the outer surface of the support. Through the connection with the support, the expansion of water to the inside of the support is limited, which does not affect the opening and closing of the valve and also does not affect the opening area. At the same time, the edge of the semi-permeable membrane is a free end, and the width of the free end edge is 0.1-2mm. The free end and the free surface provide a skirt volume expansion space for filling the gap between the valve and the autologous structure, thereby reducing the risk of paravalvular leakage.

[0034] 2. The skirt function changes through changes in the environment, such as the air environment changing into a blood environment. The selective permeation function of the semi-permeable membrane bag can only be opened in this way, avoiding the qualitative change of the membrane bag inside the air environment, and the use environment has high specificity.

[0035] 3. By supplementing the water-soluble adhesive in the membrane bag, the free movement of the membrane bag can be limited before release, and the difficulty of recovery caused by the free movement of the membrane bag can be avoided. After release, the volume of the membrane bag is expanded, and at the same time has the self-adaptability of the liquid, which well fills the gap between the valve and the autologous structure. The free flow of the liquid also does not produce pressure on the contacted part, which affects the conduction block.

[0036] 4. Medical staff can adjust the salt content according to the patient's own condition, and can effectively adjust the self-adaptive volume without increasing the loading volume, thereby further reducing the possibility of conduction block. BRIEF DESCRIPTION OF DRAWINGS

[0037] Figure 1 It is a structure diagram of the valve skirt;

[0038] Figure 2 It is a surface morphology diagram of the initial state of the coating in the embodiment;

[0039] Figure 3 It is a surface morphology diagram of the coating in the embodiment after the membrane bag is placed in the buffer solution for 60 minutes;

[0040] Figure 4 Coating surface topography of the film pouch immersed in the buffer solution for 80 minutes in the example. DETAILED DESCRIPTION

[0041] The embodiments of the present application will be described in detail below with reference to the drawings and examples, so that the technical means applied by the present application to solve the technical problems and achieve the corresponding technical effects can be fully understood and implemented. The embodiments of the present application and various features in the examples can be combined with each other without conflict, and the technical solutions formed thereby are all within the protection scope of the present application.

[0042] It should be clear that the examples described below are only some of the embodiments of the present application, not all. All other embodiments obtained by those skilled in the art based on the embodiments in the present application without creative labor are within the scope of protection of the present application.

[0043] Example 1: This embodiment describes the scheme of the adaptive valve skirt in detail:

[0044] 1. Preparation of skirt material: cutting of the membrane: commercially available Dow RO membrane is cut to form two rectangular membrane pieces of 91 mm * 10 mm.

[0045] 2. Preparation of coating solution: 1 g of polylactic acid with a molecular weight of 4000-8000 is dissolved in 10 ml of a mixed solution of dichloroethane and ethyl acetate (20% dichloroethane).

[0046] 3. Preparation of coating: 1 ml of coating solution is evenly applied to the surface of the RO membrane. After natural drying, the coating is applied back and forth 4 times.

[0047] 4. Water permeability test of the coating: place the membrane on a reverse osmosis test device and apply a pressure of 0.5 MPa. Collect the water passing through in 10 minutes. If water passes through, it is unqualified.

[0048] 5. Preparation of water-soluble glue: dissolve 1 g of polyvinyl alcohol, 6 g of starch hydrolysis glue, and 0.021 g of NaCl in 6 ml of water. Increase the temperature to 50°C and stir until fully dissolved.

[0049] 6. Preparation of the film pouch: evenly apply the water-soluble glue prepared in step 2 to the rough surface, leaving a 1 mm blank at the edge. Place the other rectangular membrane piece with the smooth surface facing up and the rough surface facing the glue on the membrane piece with the glue, aligning the edges. Then place the film pouch in a 37°C oven for 3 hours. Seal the edges of the film pouch with a sealing machine. Verify the performance of the film pouch.

[0050] 7. Test of the film bag performance: thickness, the test result shows 128-136 microns, the average is 130 microns.

[0051] 8. Test of the coating degradation rate: configure phosphate buffer solution (PBS, pH 7.4), and add bovine serum albumin (45 g / L) therein. Put the film bag into the buffer solution, take it out every 20 min to check the surface morphology, water permeability and mass gain, and the result is shown in Table 1. From the result, the initial thickness of the film bag is about 130 microns, which is much thinner than the current commonly used heart cell membrane (200-300 microns), and smaller size interventional instruments can be used in the loading process. From the micrograph of the film bag surface (Fig. 1), Figures 2-4 ), the polylactic acid is not completely degraded in the blood, but the polylactic acid generates microcracks in the degradation process, which is sufficient to form a water channel and support the recovery of the RO membrane function.

[0052] Table 1. Statistics table of coating degradation rate result

[0053]

[0054] Example 2: This example provides a scheme of self-adaptive valve skirt different from example 1

[0055] 1. Preparation of skirt material: cutting of film sheet: commercially available Dow RO membrane is cut to form a 91 mm*10 mm rectangular film sheet*2.

[0056] 2. Configuration of coating solution: 1 g of chitosan powder is dissolved in 100 ml of acetic acid solution, and magnetic stirring is carried out at 50°C until complete dissolution (about 2-4 hours), and the pH is adjusted to 4-6 (a dilute NaOH solution can be used), and then the nanocellulose is dispersed in water (1% w / v), and ultrasonic treatment is carried out for 20-30 minutes, and the power is 300 W to avoid agglomeration. The nanocellulose and the dispersion are slowly added to the chitosan solution (mass ratio is 1:5), and stirring is carried out while ultrasonic treatment is carried out for 20-30 minutes, and the power is 300 W.

[0057] 3. Preparation of coating, 1000-3000 rpm rotation of film sheet, 1 ml of coating solution is evenly coated on the surface of the RO membrane, and natural drying is carried out, and the coating is carried out back and forth for 12 times.

[0058] 4. Test of water permeability of coating: the film sheet is placed on a reverse osmosis test device, and a pressure of 0.5 MPa is applied, and the water passing through in 10 min is collected, and if water passes through, it is unqualified.

[0059] 5. Configuration of water-soluble glue: 1 g of polyvinyl alcohol, 6 g of starch and 0.021 g of NaCl hydrolysis glue are dissolved in 6 ml of water, the temperature is increased to 50°C, and stirring is carried out until complete dissolution.

[0060] 6. Preparation of the film bag: evenly spread the water-soluble glue prepared in step 2 on the rough surface, leaving a 1mm gap at the edge, and then place another rectangular film piece on the film piece with the smooth surface facing up and the rough surface facing the glue, aligning the edges. Then place the film bag in a 37°C oven for 3h. Seal the edges of the film bag with a 1mm gap using a sealing machine. Verify the performance of the film bag.

[0061] 7. Test the performance of the film bag: the thickness is tested using a thickness gauge, and the results show that the thickness is 135-142 microns, with an average of 138 microns.

[0062] 8. Test the degradation rate of the coating: prepare a phosphate buffer solution (PBS, pH 7.4) and add bovine serum albumin (45g / L) to it. Place the film bag in the buffer solution and check the water permeability and mass gain every 20min, and the results are shown in Table 1. Figure 2

[0063] The difference between this example and Example 1 is the use of a different degradation coating. This relatively faster hydrolysis rate of the degradation coating allows the semi-permeable membrane to be restored for use in a shorter period of time. The statistical results of the coating degradation rate of this example are shown in Table 2.

[0064] Table 2 Statistical results of the coating degradation rate

[0065]

[0066] Example 3: This example further explores the relationship between the content of inorganic salts and the water absorption of the film bag

[0067] 1. Preparation of the skirt material: cut the film piece: use commercially available Dow RO membranes to cut into rectangular film pieces of 91mm*10mm*2.

[0068] 2. Preparation of the coating solution: dissolve 1g of polylactic acid with a molecular weight of 4000-8000 in 10ml of a mixture of dichloroethane and ethyl acetate (20% dichloroethane).

[0069] 3. Preparation of the coating: evenly apply 1ml of the coating solution to the surface of the RO membrane, and allow it to dry naturally. Repeat this process 4 times.

[0070] 4. Test the water permeability of the coating: place the film piece on a reverse osmosis testing device and apply a pressure of 0.5MPa. Collect the water that passes through within 10min. If water passes through, it is unqualified.

[0071] ​5. Preparation of water-soluble glue: 1 g of polyvinyl alcohol, 6 g of starch hydrolysis glue, and 0.035 g of NaCl were dissolved in 6 ml of water, and the temperature was raised to 50°C, and stirred until fully dissolved.

[0072] 6. Preparation of the film bag: the water-soluble glue prepared in step 2 was evenly applied to the rough surface, leaving a 1 mm blank at the edge, and another piece of rectangular film was placed on top of the film with the smooth surface facing up and the rough surface facing the glue, and the edges were aligned. Then the film bag was placed in a 37°C oven for 3 h. The edges of the film bag were sealed with a sealing machine. The performance of the film bag was verified.

[0073] 7. Test of the performance of the film bag: the thickness was tested with a thickness gauge, and the results showed that the thickness was 131-142 microns, with an average of 134 microns.

[0074] 8. Test of the degradation rate of the coating: phosphate buffer solution (PBS, pH 7.4) was prepared and bovine serum albumin (45 g / L) was added. The film bag was placed in the buffer solution, and the water permeability and mass gain were checked every 20 min, and the results are shown in Figure 3

[0075] By comparing Example 1 and this example, it can be found that by adjusting the content of inorganic salt, the water absorption of the film bag can be significantly increased, and thus the self-adaptability of the film bag can be adjusted. The statistical results of the coating degradation rate of this example are shown in Table 3.

[0076] Table 3 Statistical results of the coating degradation rate

[0077]

[0078] Example 4: Effect of coating thickness on use

[0079] 1. Preparation of the skirt material: cutting of the film: commercially available Dow RO membrane was cut to form two rectangular film pieces with dimensions of 91 mm * 10 mm.

[0080] 2. Preparation of the coating solution: 1 g of polylactic acid with a molecular weight of 4000-8000 was dissolved in 10 ml of a mixture of dichloroethane and ethyl acetate (20% dichloroethane).

[0081] 3. Preparation of the coating: 1 ml of the coating solution was evenly applied to the surface of the RO membrane, and then naturally dried, and the process was repeated 6 times.

[0082] 4. Test of the water permeability of the coating: the film was placed on a reverse osmosis test device, and a pressure of 0.5 MPa was applied, and the water passing through in 10 min was collected. If water passed through, it was unqualified.

[0083] ​5. Preparation of water-soluble glue: 1 g of polyvinyl alcohol, 6 g of starch hydrolysis glue, and 0.021 g of NaCl were dissolved in 6 ml of water, and the temperature was raised to 50°C, and stirred until fully dissolved.

[0084] 6. Preparation of the film bag: The water-soluble glue prepared in step 2 was evenly applied to the rough surface, leaving a 1 mm blank at the edge, and the other piece of rectangular film was placed on top of the film with the smooth surface facing up and the rough surface facing the glue, with the edges aligned. Then the film bag was placed in a 37°C oven for 3 h. The edges of the film bag were sealed with a sealing machine. The performance of the film bag was verified.

[0085] 7. Test of the performance of the film bag: The thickness was tested with a thickness gauge, and the results showed that the thickness was 140-153 microns, with an average of 146 microns.

[0086] 8. Test of the degradation rate of the coating: Phosphate buffer solution (PBS, pH 7.4) was prepared and bovine serum albumin (45 g / L) was added. The film bag was placed in the buffer solution, and the water permeability and mass gain were checked every 20 min, and the results are shown in Table 3. Figure 4

[0087] The difference between this example and Example 1 is that the number of times the RO membrane surface is coated with the degradable coating is increased, and the degradable coating is thickened. This thickening of the coating is also reflected in the overall thickness, which increases from 130 microns in Example 1 to 146 microns. At the same time, the degradation time is also significantly increased, which can provide sufficient time for the operation. The water absorption of the final film bag is not much different from that of Example 1, indicating that the thickness of the degradable coating has limited effect on the final water absorption of the film bag. The statistical results of the coating degradation rate of this example are shown in Table 4.

[0088] Table 4 Statistical results of the coating degradation rate

[0089] ​

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 coated with a degradable coating with closed pores; The water-soluble adhesive is starch hydrolyzed gelatin and polyvinyl alcohol; the upper semipermeable membrane and the lower semipermeable membrane are both RO membranes.

2. 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.

3. The adaptive valve skirt according to claim 2, characterized in that: The inorganic salt is sodium chloride, and the amount used is 0.05mmol-2.40mmol.

4. 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%.

5. 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, and chitosan-nanocellulose.

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

7. 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.

8. 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.

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