Dry valve leaflet and preparation method thereof, valve

Abstract

The present application provides a dry leaflet, a preparation method thereof, and a valve, belonging to the field of medical material technology. The preparation method of the dry leaflet comprises: cross-linking, modifying, dehydrating, and drying an animal pericardium sheet with glutaraldehyde. The modification comprises: treating the cross-linked animal pericardium with Tween-80 and glycine. This method can reduce the content of aldehyde groups and phospholipid substances in the final leaflet to a certain extent, thereby improving the anti-calcification effect of the leaflet; at the same time, the treatment with Tween-80 and glycine will basically not affect the structure of the pericardium sheet, so that the mechanical properties of the leaflet can be maintained to a certain extent.

Description

Technical Field

[0001] The present application relates to the field of medical material technology, and in particular to a dry valve leaflet, a preparation method thereof, and a valve. Background Art

[0002] Traditional heart valve replacement surgery is an open, highly invasive procedure that involves significant surgical trauma and requires extracorporeal circulation. The surgical risk is high, and adverse reactions such as massive bleeding, infection, and arrhythmia are common during surgery, requiring patients to take months to recover. While transapical aortic valve replacement incurs minimal incision, it still causes trauma to the patient's heart, leading to prolonged pain during recovery. In recent years, researchers have been working to minimize trauma by performing artificial heart valve replacements without opening the chest or placing the patient on extracorporeal circulation. This bioprosthetic valve can be placed through the patient's own valve, thus avoiding the need to remove the patient's diseased valve.

[0003] An artificial heart valve includes a valve stent, leaflets and a skirt. The leaflets and the skirt are installed on the valve stent, and the leaflets are located in the space formed by the valve stent. The leaflets open to open the blood channel of the artificial heart valve, and the leaflets close to close the blood channel of the artificial heart valve, thereby replacing the diseased valve.

[0004] Because the valve leaflets are crucial components for replacing diseased heart valves, their performance is crucial. Existing valve leaflets are made by treating bovine or porcine pericardium with glutaraldehyde. Over time, these leaflets can calcify, affecting the opening and closing of the valve and hindering the use of artificial heart valves. Summary of the Invention

[0005] Research has found that the reason why the leaflets cannot close and the leaflets calcify is that the leaflets are obtained by cross-linking the pericardium with glutaraldehyde. During the cross-linking process using glutaraldehyde, the glutaraldehyde reaction may be incomplete, resulting in residual aldehyde groups on the pericardium. Since the residual aldehyde groups are negatively charged, they are easily electrostatically adsorbed by calcium ions contained in the human environment. During the use of the valve, the calcium ions combine with the aldehyde groups in the leaflets and accumulate in the leaflets, leading to calcification.

[0006] The present application provides a dry valve leaflet, a preparation method thereof, and a valve. The dry valve leaflet prepared by the preparation method has a better anti-calcification effect and can maintain mechanical properties to a certain extent.

[0007] In a first aspect, the present application provides a method for preparing a dry valve leaflet, comprising: cross-linking an animal pericardium sheet with glutaraldehyde, modifying, dehydrating, and drying the sheet, wherein the modification comprises treating the cross-linked pericardium sheet with Tween-80 and glycine.

[0008] Research has also found that, in addition to the use of glutaraldehyde causing leaflet calcification, phospholipids contained in the leaflets are a major cause of leaflet calcification during use. Therefore, the modification of the cross-linked pericardium sheet using Tween-80 and glycine in this application can remove some of the phospholipids in the sheet while neutralizing some of the aldehyde groups, thereby improving the leaflet's anti-calcification effect. Furthermore, Tween-80 and glycine have little effect on the structure of the sheet, allowing the mechanical properties of the leaflets to be maintained to a certain extent.

[0009] In some embodiments, the modification includes anti-calcification and neutralization, wherein the anti-calcification comprises: immersing the cross-linked pericardium sheet in a buffer solution containing ethanol and Tween-80. The neutralization comprises: immersing the anti-calcified pericardium sheet in a glycine aqueous solution.

[0010] In this application, the use of a buffer solution containing Tween-80 and ethanol to impregnate the pericardium sheet after glutaraldehyde cross-linking can effectively elute the phospholipid substances in the pericardium sheet, so that the valve leaflet has a certain anti-calcification effect; at the same time, after the pericardium sheet is impregnated with a buffer solution containing Tween-80 and ethanol, the aldehyde groups in the treated pericardium sheet can be more easily reacted with glycine in the glycine aqueous solution, thereby significantly reducing the content of aldehyde groups and phospholipid substances in the final valve leaflet, thereby improving the anti-calcification effect of the valve leaflet. At the same time, the Tween-80 and ethanol added during the anti-calcification treatment can also have a certain antibacterial and antibacterial effect, so that the anti-calcification treatment can be carried out under sterile conditions, so that while eluting the phospholipid substances, it will basically not affect the structure of the pericardium sheet, and the mechanical properties of the valve leaflet are better.

[0011] In some embodiments, the volume percentage of ethanol in the buffer solution is 20% to 60%, and the volume percentage of Tween-80 is 0.6% to 2%. The small amount of Tween-80, when combined with ethanol and the buffer solution, can effectively elute phospholipids and promote the reaction of aldehyde groups with glycine.

[0012] In some embodiments, the anti-calcification conditions include: immersing the pericardium sheet at a temperature of 40°C to 50°C for 3 to 12 hours. Immersing the pericardium sheet at the aforementioned temperature and for the aforementioned time can improve the treatment effect of the pericardium sheet, further enhancing the elution of phospholipids and promoting the reaction between aldehyde groups and glycine.

[0013] In some embodiments, the mass concentration of the glycine aqueous solution is 4% to 20%. Because the pericardium sheet has been impregnated with a buffer solution containing Tween-80 and ethanol, most of the aldehyde groups in the pericardium sheet can be neutralized even with a low glycine content, thereby effectively treating the pericardium sheet and improving the anti-calcification effect of the valve leaflets.

[0014] In some embodiments, the neutralization conditions include: immersion at a temperature of 2°C to 8°C for 3h to 2d. Generally speaking, when performing a chemical reaction, the higher the reaction temperature, the faster the reaction. In the present application, since the pericardium sheet has been immersed in a buffer solution containing Tween-80 and ethanol, it can be immersed in a glycine aqueous solution at a lower temperature during the neutralization step. This can not only achieve the neutralization of the aldehyde group, but also react at a lower temperature to control the amount of bioburden on the leaflet to a certain extent, and also avoid the effect of excessively high reaction temperature on the mechanical properties of the leaflet.

[0015] In some embodiments, dehydration includes immersing the leaflets in a low-concentration ethanol solution and a high-concentration ethanol solution at room temperature for 5 to 20 minutes, respectively; the low-concentration ethanol solution must contain 30% or more ethanol by volume. Drying includes immersing the leaflets in a mixture of glycerol and ethanol at room temperature for 1 to 2 days. Combining dehydration and drying significantly shortens the dehydration time. Drying can also help maintain the leaflets' dehydrated state and, to a certain extent, mitigate the effects of prolonged immersion in a high-concentration ethanol solution on their mechanical properties.

[0016] In some embodiments, the volume percentage of ethanol in the low-concentration ethanol-water solution is 30% to 60%; the volume percentage of ethanol in the high-concentration ethanol-water solution is 70% to 90%; and the volume percentage of glycerol in the glycerol-ethanol mixture is 70% to 90%. These concentrations of ethanol solution are used for gradient dehydration, and the higher the glycerol concentration during drying, the easier it is to obtain a dry leaflet, while also preserving the leaflet's mechanical properties.

[0017] In a second aspect, the present application provides a dry leaflet, prepared by the method for preparing a dry leaflet provided in any one of the first aspects. The dry leaflet obtained by this preparation method can be transported and stored under dry conditions, and has good anti-calcification effects and maintained mechanical properties.

[0018] In a third aspect, the present application provides a valve comprising a valve support and leaflets, wherein the leaflets are fixed to the valve support, and the leaflets are the infiltrated dry leaflets provided in the second aspect. During use, the valve has a better anti-calcification effect and can extend its service life.

[0019] In some embodiments, the valve is a balloon-expandable valve. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art.

[0021] Figure 1A process flow chart of a method for preparing a dry leaflet provided in an embodiment of the present application;

[0022] Figure 2 A schematic diagram of detecting the calcium content of a dry leaflet provided in an embodiment of the present application;

[0023] Figure 3 A leaflet width test diagram showing the tensile performance of a dry leaflet provided in an embodiment of the present application;

[0024] Figure 4 Schematic diagram of leaflet clamping showing the tensile performance of the dry leaflet provided in an embodiment of the present application. DETAILED DESCRIPTION

[0025] Currently, most studies believe that the anti-calcification properties of the valve leaflets are affected by residual aldehyde groups and unreacted glutaraldehyde (which contains aldehyde groups) in the leaflets. Therefore, existing methods often treat these aldehyde groups to improve the anti-calcification effect of the leaflets by reducing their content. However, further research by the inventors has found that simply treating the aldehyde groups does not effectively improve the anti-calcification properties of the leaflets. Phospholipids contained in the leaflets also affect the anti-calcification properties of the leaflets.

[0026] Therefore, the present application provides a method for preparing a dry valve leaflet, comprising: cross-linking an animal pericardium sheet with glutaraldehyde, modifying, dehydrating, and drying the sheet, wherein the modification comprises treating the cross-linked pericardium sheet with Tween-80 and glycine.

[0027] The modified treatment of the cross-linked pericardium sheet with Tween-80 and glycine in this application can remove some phospholipids from the sheet while neutralizing some aldehyde groups, thereby improving the anti-calcification effect of the valve leaflets. Furthermore, Tween-80 and glycine have little effect on the structure of the sheet, maintaining the mechanical properties of the valve leaflets to a certain extent.

[0028] The preparation method provided in this application is described in detail below. Figure 1 For a process flow chart of the method for preparing the dry leaflet provided in the embodiment of the present application, please refer to Figure 1 , the preparation method comprises:

[0029] S110 Pretreatment of animal pericardium: rinse the animal pericardium with physiological saline, cut the rinsed animal pericardium, spread it out on a backlight board, and select to cut out blocks of preset size to obtain animal pericardium slices.

[0030] Optionally, the animal pericardium can be bovine pericardium, porcine pericardium, sheep pericardium, etc., preferably bovine pericardium. During the rinsing process, the physiological saline needs to be replaced until the physiological saline is clear.

[0031] Optionally, when selecting a block of a preset size, a block with a relatively uniform thickness and without blood streaks or blood spots may be selected.

[0032] S120 Glutaraldehyde cross-linking of animal pericardial slices: immersing the cut pericardial slices in a glutaraldehyde buffer solution at room temperature for 2 days to 7 days; wherein the volume proportion of glutaraldehyde is 0.3% to 0.625%.

[0033] Optionally, both ends of the pericardial piece can be fixed vertically, and then multiple pericardial pieces can be spaced about 1 cm apart and then immersed together in a glutaraldehyde buffer solution to perform cross-linking treatment on the multiple pericardial pieces.

[0034] In the present application, the buffer solution is a PBS buffer solution or a HEPES buffer solution. The volume proportion of glutaraldehyde in the glutaraldehyde buffer solution is 0.3%, 0.4%, 0.5%, 0.6% or 0.625%. The pericardium slice is immersed in the glutaraldehyde buffer solution at room temperature for 2 days, 3 days, 4 days, 5 days, 6 days or 7 days.

[0035] S130 anti-calcification: The cross-linked pericardium slices were immersed in a buffer solution containing ethanol and Tween-80.

[0036] Using a buffer solution containing Tween-80 and ethanol to impregnate the glutaraldehyde-crosslinked pericardium sheet effectively elutes phospholipids within the sheet, thereby imparting a certain degree of anti-calcification effect to the leaflets. Furthermore, impregnation of the pericardium sheet with a buffer solution containing Tween-80 and ethanol makes the aldehyde groups in the treated sheet more susceptible to reaction with glycine in the glycine aqueous solution, significantly reducing the content of aldehyde groups and phospholipids in the final leaflets, thereby enhancing the leaflet's anti-calcification effect. Furthermore, the Tween-80 and ethanol added during the anti-calcification treatment also have certain antibacterial and antimicrobial effects, allowing the anti-calcification treatment to be performed under sterile conditions. This allows for the elution of phospholipids without affecting the performance of the pericardium sheet, thereby enhancing the mechanical properties of the leaflets.

[0037] Optionally, the volume proportion of ethanol in the buffer solution is 20% to 60%; the volume proportion of Tween-80 is 0.6% to 2%. The small amount of Tween-80, when combined with ethanol and the buffer solution, can effectively elute phospholipids and promote the reaction between aldehyde groups and glycine.

[0038] Illustratively, the buffer solution is PBS buffer solution or HEPES buffer solution; the volume proportion of ethanol is 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55% or 60%; and the volume proportion of Tween-80 is 0.6%, 1%, 1.5% or 2%.

[0039] Optionally, the anti-calcification conditions include: immersing the pericardium sheet at a temperature of 40°C to 50°C for 3 to 12 hours. Immersing the pericardium sheet at the above temperature and for the above time can improve the treatment effect of the pericardium sheet, further enhance the elution of phospholipid substances and promote the reaction between aldehyde groups and glycine.

[0040] Illustratively, the temperature of the anti-calcification immersion is 40°C, 42°C, 44°C, 46°C, 48°C or 50°C; the time of the anti-calcification immersion is 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 11h or 12h.

[0041] S140 Neutralization: The anti-calcified pericardium pieces are immersed in a glycine aqueous solution. Because the pericardium pieces have been immersed in a buffer solution containing Tween-80 and ethanol, the addition of a glycine aqueous solution for neutralization can better neutralize the aldehyde groups, thereby improving the anti-calcification properties of the valve leaflets.

[0042] Optionally, the mass concentration of the glycine aqueous solution is 4% to 20%. Since the pericardium sheet has been impregnated with a buffer solution containing Tween-80 and ethanol, most of the aldehyde groups in the pericardium sheet can be neutralized even with a low glycine content, thereby effectively treating the pericardium sheet and improving the anti-calcification effect of the valve leaflet.

[0043] Illustratively, the mass concentration of the glycine aqueous solution is 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18% or 20%.

[0044] Optionally, the neutralization conditions include: immersion at a temperature of 2°C to 8°C for 3h to 2d. Generally speaking, when performing a chemical reaction, the higher the reaction temperature, the faster the reaction. In the present application, since the pericardium sheet has been immersed in a buffer solution containing Tween-80 and ethanol, it can be immersed in a glycine aqueous solution at a lower temperature during the neutralization step, which can not only achieve the neutralization of the aldehyde group, but also react at a lower temperature, thereby avoiding, to a certain extent, the impact of excessively high reaction temperature on the performance of the valve leaflet.

[0045] As an example, the neutralization immersion temperature is 2°C, 3°C, 4°C, 5°C, 6°C, 7°C or 8°C; the neutralization immersion time is 3h, 5h, 10h, 25h, 1d, 1.5d or 2d.

[0046] S150 dehydration: soaking in low-concentration ethanol aqueous solution and high-concentration ethanol aqueous solution at room temperature for 5 minutes to 20 minutes respectively; and the volume proportion of ethanol in the low-concentration ethanol aqueous solution is ≥30%.

[0047] Alternatively, the neutralized pericardium sheet can be immersed in a low-concentration ethanol-water solution at room temperature for 5 to 20 minutes, followed by immersion in a high-concentration ethanol-water solution at room temperature for 5 to 20 minutes. The low-concentration ethanol-water solution (the solvent is water) contains 30% to 60% ethanol by volume, while the high-concentration ethanol-water solution (the solvent is water) contains 70% to 90% ethanol by volume. This treatment removes a significant amount of water from the pericardium sheet without affecting the mechanical properties of the resulting valve leaflet. Combined with subsequent drying, a dry valve can be obtained.

[0048] Illustratively, the volume proportion of ethanol in the low-concentration ethanol aqueous solution is 30%, 35%, 40%, 450%, 50%, 55% or 60%; the immersion time of the low-concentration ethanol aqueous solution at room temperature is 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, 15 min or 20 min; the volume proportion of ethanol in the high-concentration ethanol aqueous solution is 70%, 72%, 74%, 76%, 78%, 80%, 85% or 90%; the immersion time of the high-concentration ethanol aqueous solution at room temperature is 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, 15 min or 20 min.

[0049] S160 drying: immersing in a mixture of glycerol and ethanol at room temperature for 1 to 2 days. Optionally, the volume proportion of glycerol in the mixture of glycerol and ethanol is 70% to 90%.

[0050] The combination of dehydration and drying can significantly shorten the dehydration time. At the same time, drying can achieve better dehydration effect and avoid the influence of long-term immersion in high-concentration ethanol solution on the mechanical properties of the leaflet to a certain extent.

[0051] Illustratively, in the mixture of glycerol and ethanol, the volume proportion of glycerol is 70%, 75%, 80%, 82%, 84%, 86%, 88% or 90%; the immersion time at room temperature is 1d, 1.2d, 1.4d, 1.6d, 1.8d or 2d.

[0052] S180 sterilization: The sterilization method is EO sterilization.

[0053] The dry leaflet prepared by the above method can be transported and stored under dry conditions. In addition, the leaflet has a good anti-calcification effect and is easy to store under sterile conditions.

[0054] After infiltration, the dry leaflet can be fixed on a valve stent to prepare a valve. The valve can replace the diseased valve, has good anti-calcification effect, and has a long service life. At the same time, the valve can be a balloon-expandable valve, which is convenient for delivery to the diseased area.

[0055] Example

[0056] A method for preparing a dry valve, comprising:

[0057] (1) Rinse the animal pericardium with physiological saline, and replace the physiological saline every 10 minutes until the physiological saline is clear. Cut the rinsed animal pericardium open, spread it out and place it on a backlight board. Select an area with relatively uniform thickness and no blood spots, and cut out a 10 cm × 10 cm block.

[0058] (2) The two ends of the pericardium piece were fixed vertically and immersed in a PBS buffer solution with a volume concentration of 0.5% glutaraldehyde at room temperature for 4 days.

[0059] (3) Anti-calcification: The cross-linked pericardium slices were immersed in a buffer solution containing ethanol and Tween-80; the specific conditions are shown in Table 1.

[0060] (4) Neutralization: The anti-calcified pericardium slices were immersed in a glycine aqueous solution; the specific conditions are shown in Table 1.

[0061] (5) Dehydration: Soak in low-concentration ethanol aqueous solution and high-concentration ethanol aqueous solution at room temperature for 5 min to 20 min respectively; the volume proportion of ethanol in the low-concentration ethanol aqueous solution shall be ≥30%; the specific conditions are shown in Table 1.

[0062] (6) Drying: Soak in a mixture of glycerol and ethanol at room temperature for 1 to 2 days; the specific conditions are shown in Table 1.

[0063] (7) Sterilization: The sterilization method is EO sterilization.

[0064] Table 1 Preparation conditions of dry leaflets

[0065]

[0066]

[0067]

[0068] The dry leaflet is obtained by the above-mentioned treatment, and the performance of the dry leaflet is tested as follows:

[0069] (1) Calcium content

[0070] 1.1 Sample preparation: Rinse the dry leaflets provided in the example and comparative example with 500 mL of sterile physiological saline for three times, each time for 1 minute.

[0071] 1.2 Animal anesthesia: Rats were anesthetized with intraperitoneal injection of sodium pentobarbital at a dose of 40 mg / kg.

[0072] 1.3 Implantation steps: Remove the dorsal hair of the experimental rats, disinfect with iodine, and press the Figure 2 Subcutaneous implantation was performed as shown. One sample was implanted on the left side and one on the right side. After implantation, routine suturing and disinfection were performed.

[0073] 1.4 Test period: 8 weeks.

[0074] 1.5 Gross sampling: After 8 weeks of implantation, the experimental rats were sacrificed, the skin was opened to fully expose the sample implantation site, and the sample was taken out from the subcutaneous tissue. The host tissue on the implant surface was carefully removed, and the implant was rinsed with saline and smoothed.

[0075] 1.6 Sample Preparation and Calcium Content Testing: Dry the sample to constant weight at 80°C. Accurately weigh one sample (accurate to 0.00001g) and place it in the digestion tank. Add 5mL of nitric acid. Cover the safety valve, install the protective cover, and place the digestion tank on a hot plate for heating and digestion. After the sample digestion is complete, remove the tank and transfer the digestion solution to a 25mL volumetric flask. Rinse the inner tank wall several times with small amounts of water and transfer the solution to the volumetric flask. Dose to the mark with purified water and mix thoroughly to prepare the sample solution. Prepare a blank solution without the sample in the same manner. If the calcium content of the sample solution is too high, dilute the sample solution as needed before testing.

[0076] 1.7 Turn on the inductively coupled plasma spectrometer (ICP), establish the analytical method and sample information for calcium determination, and establish the corresponding working curve range. Prepare a series of calcium standard solutions at concentrations of 0 mg / L, 2 mg / L, 4 mg / L, 6 mg / L, 8 mg / L, and 10 mg / L. Measure the standard solutions in ascending concentrations, allowing the computer to automatically plot a standard working curve. Calibrate with a blank solution before measuring the sample solution. Calculate the calcium content of the sample based on the sample mass and solution volume using the measured calcium concentrations.

[0077] (2) Tensile properties

[0078] 2.1 Measure the width X of the sample test section provided in the examples and comparative examples (according to Figure 3 The positions shown were measured three times and the average value was taken).

[0079] 2.2 Use medical packaging performance tester to test according to Figure 4 Place the wide end of the specimen into the upper fixture as shown, then rotate the upper fixture to clamp it, allowing the specimen to hang freely into the lower fixture, and then rotate the lower fixture to clamp the other end of the specimen.

[0080] 2.3 Select the corresponding test mode in the parameter settings of the main interface, set the stretching rate to 10 mm / min, submit the width X, and click "Start Test" in the experimental control of the main interface to start the test.

[0081] 2.4 After the specimen breaks, the upper grip automatically returns to its original position, and the test ends. View the test image and read the maximum tensile force in the image.

[0082] (3) Water content

[0083] 3.1 Cut the dry leaflets provided in the embodiment and comparative example, put them into an aluminum box of known weight, and weigh them (Wf).

[0084] 3.2 Place the dry leaflets together with the aluminum box in an oven heated to 70°C, dry them to constant weight, and weigh the dry weight (Wd).

[0085] 3.3 The formula for calculating moisture content is (Wf-Wd) / Wf×100%.

[0086] The performance test results of the dry valve leaflet are shown in Table 2:

[0087] Table 2 Performance of dry leaflets

[0088]

[0089]

[0090] From Table 1 and Table 2, it can be seen that after the dry valve leaflets provided in the embodiment of the present application were implanted in rats for 8 weeks, the calcium content in the digestion liquid after the dry valve leaflets were taken out and digested can be significantly reduced, indicating that the dry valve leaflets provided in the embodiment of the present application have a better anti-calcification effect.

[0091] From the comparison of Examples 1 to 4, it can be seen that the concentration of Tween-80 will affect the anti-calcification effect of the dry valve leaflet. When the volume proportion of Tween-80 is 1% to 2%, the anti-calcification effect of the dry valve leaflet is better; when the volume proportion of Tween-80 is 2.5%, the anti-calcification effect of the dry valve leaflet is basically no longer improved, but the processing cost will increase.

[0092] From the comparison of Example 1 and Examples 5 to 8, it can be seen that if the concentration of ethanol is too high, the mechanical properties of the dry valve leaflet will be affected to a certain extent; if the concentration of ethanol is too low, the anti-calcification effect of the dry valve leaflet will be affected to a certain extent. Therefore, when the volume proportion of ethanol is 20% to 60%, the anti-calcification effect of the dry valve leaflet can be better.

[0093] Comparison of Example 1 and Examples 9 to 10 shows that a mass concentration of glycine of 4% to 20% can achieve a better anti-calcification effect of the dry valve leaflet.

[0094] Comparison between Example 1 and Example 11 shows that, in the dehydration process, if the dehydration time is too long, the mechanical properties of the dry leaflet will be affected, and the water content will basically not decrease.

[0095] From the comparison between Example 1 and Example 12, it can be seen that in the drying process, if the drying time is short, the water content of the dry leaflet may increase to a certain extent.

[0096] Comparison of Example 1 with Example 13 shows that if Tween-80, ethanol and glycine are mixed and subjected to anti-calcification and neutralization treatment in one step, the dry leaflet can still have a good anti-calcification effect; however, its mechanical properties will be affected to a certain extent.

[0097] The above description is merely a preferred embodiment of the present application and is not intended to limit the present application. Various modifications and variations are possible for those skilled in the art. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present application shall be included within the scope of protection of the present application.

Claims

1. A method for preparing a dry leaflet, characterized in that: include: Animal pericardial slices were cross-linked with glutaraldehyde, modified, dehydrated, and dried; Wherein, the modification comprises: treating the cross-linked pericardium sheet with Tween-80 and glycine; The modifications include anti-calcification and neutralization; The anti-calcification method comprises: immersing the cross-linked pericardium sheet in a buffer solution containing ethanol and Tween-80; in the buffer solution, the volume proportion of the ethanol is 20% to 60%; the volume proportion of the Tween-80 is 0.6% to 2%; The neutralization comprises: immersing the anti-calcified pericardium sheet in a glycine aqueous solution; the mass concentration of the glycine aqueous solution is 4% to 20%; The dehydration comprises: immersing in low concentration ethanol aqueous solution and high concentration ethanol aqueous solution at room temperature for 5 minutes to 20 minutes respectively; The drying process comprises: immersing the mixture of glycerol and ethanol at room temperature for 1 to 2 days; The volume proportion of ethanol in the low-concentration ethanol aqueous solution is 30% to 60%; the volume proportion of ethanol in the high-concentration ethanol aqueous solution is 70% to 90%; in the mixed solution of glycerol and ethanol, the volume proportion of glycerol is 70% to 90%; The anti-calcification conditions include: immersing at a temperature of 40°C to 50°C for 3h to 12h; The neutralization conditions include: immersing at a temperature of 2° C. to 8° C. for 3 h to 2 d.

2. A dry leaflet, characterized in that: The method according to claim 1 is used to prepare the present invention.

3. A valve, characterized in that: The valve comprises a valve support and a valve leaflet, wherein the valve leaflet is fixed to the valve support, and the valve leaflet is the dry valve leaflet according to claim 2 after being infiltrated; The valve is a balloon-expandable valve.

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