Biological tissue sealing material and preparation method thereof

Abstract

The invention provides a tissue sealing material which is good in biocompatibility and capable of effectively and quickly sealing a wound part, and is characterized in that the tissue sealing material is spongy and is prepared from aldehyde natural polysaccharide through segmented freeze-drying. The invention also discloses a preparation method of the tissue sealing material, which comprises the following steps: S1, dissolving the aldehyde natural polysaccharide in water to prepare an aldehyde natural polysaccharide solution with the concentration of 0.5-20%, and adjusting the pH value to 7-9; s2, putting the formylated natural polysaccharide solution into a freeze dryer which is pre-cooled to-80 DEG C to-40 DEG C, and keeping for 3-12 hours; s3, setting the vacuum degree of the freeze dryer to be 0.01 to 0.5 mbar, and carrying out freeze drying for 24 to 96 hours; s4, maintaining the vacuum degree, raising the temperature to 0 DEG C at the speed of 5-15 DEG C / h, and then freeze-drying for 12-48 hours; and S5, recovering the vacuum degree to normal pressure, raising the temperature to 30-50 DEG C at the speed of 10-20 DEG C / h, and keeping the temperature for 12-24 hours, thereby obtaining the product.

Description

Technical Field

[0001] The invention belongs to the field of medical materials, and in particular relates to a biological tissue sealing material and a preparation method thereof. Background Art

[0002] Medical gauze and sponges are commonly used hemostatic and filling materials. Their mechanism of action is to absorb water from the blood through their own water absorption capacity, enrich coagulation factors to promote coagulation, or produce compression hemostasis through their own expansion and interaction with surrounding soft tissues.

[0003] However, these materials are usually suitable for minor bleeding such as oozing, and cannot effectively stop heavy bleeding. They rely on the patient's own blood coagulation and are ineffective for patients with coagulation disorders. At the same time, these materials cannot effectively seal the wound site. After application, the wound will still continue to ooze blood and the tissue fluid will flow out. Summary of the invention

[0004] Based on the above problems, the present invention provides a biological tissue sealing material with good biocompatibility and the ability to quickly and effectively seal wound sites. The biological tissue sealing material is sponge-like and is prepared from aldehyde-modified natural polysaccharides by segmented freeze-drying.

[0005] The biological tissue sealing material provided by the present invention may also have such a technical feature, wherein the pores in the biological tissue sealing material are 1 to 20 μm, preferably 10 to 20 μm.

[0006] The biological tissue sealing material provided by the present invention may also have such technical features, wherein the water absorption of the biological tissue sealing material is less than 5g / g. The biological tissue sealing material is not easy to absorb water and swell, and when used, it reacts and cross-links with the amino / thiol groups on cells or proteins in body fluids or tissue surfaces to form a physical sealing layer, thereby sealing the wound site.

[0007] The present invention also provides a method for preparing the biological tissue sealing material as described above, characterized in that the material is prepared by a segmented freeze-drying method, comprising the following steps:

[0008] Step S1, dissolving the aldehyde-modified natural polysaccharide in water to prepare a aldehyde-modified natural polysaccharide solution with a concentration of 0.5% to 20%, and adjusting the pH to 7 to 9;

[0009] Step S2, placing the aldehyde-modified natural polysaccharide solution in a freeze dryer precooled to -80°C to -40°C for 3 to 12 hours;

[0010] Step S3, setting the vacuum degree of the freeze dryer to 0.01-0.5 mbar, and freeze drying for 24-96 hours;

[0011] Step S4, maintaining the vacuum degree, heating to 0°C at a rate of 5-15°C / hour, and then freeze-drying for 12-48 hours;

[0012] Step S5, restore the vacuum degree to normal pressure, increase the temperature to 30-50°C at a rate of 10-20°C / hour, and maintain for 12-24 hours to obtain a biological tissue sealing material.

[0013] In the method for preparing the biological tissue sealing material provided by the present invention, the precooling temperature in step S2 is preferably -55°C to -45°C.

[0014] The preparation method of the biological tissue sealing material provided by the present invention may also have such a technical feature that the aldehyde-modified natural polysaccharide is a combination of one or more of aldehyde-modified hyaluronic acid, aldehyde-modified dextran, aldehyde-modified pullulan, aldehyde-modified chitosan and aldehyde-modified carboxymethyl cellulose.

[0015] Function and Effect of the Invention

[0016] The biological tissue sealing material provided by the present invention is prepared by freeze-drying the aldehyde-modified polysaccharide in sections, so it has a dense structure and small pores. Such biological tissue sealing material is not easy to absorb water and swell. When used, once it contacts body fluids or tissue surfaces, it can react and cross-link with the amino / thiol groups on cells or proteins in the body fluids or tissue surfaces to form a physical sealing layer, thereby effectively sealing the wound site. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 is a physical photograph of the biological tissue sealing material of Example 1 of the present invention;

[0018] Figure 2 is an electron microscope photograph of the biological tissue sealing material of Example 1 of the present invention;

[0019] Figure 3 This is a physical photograph of the biological tissue sealing material of Comparative Example 1 of the present invention;

[0020] Figure 4 is an electron microscope photograph of the biological tissue sealing material of Comparative Example 1 of the present invention;

[0021] Figure 5 This is a photo of the biological tissue sealing material of Example 1 of the present invention after being immersed in pure water and polylysine solution for 30 minutes;

[0022] Figure 6 This is a photo of the hemostatic performance test of the biological tissue sealing material of Example 1 of the present invention;

[0023] Figure 7 This is a photo of the hemostatic performance test of the biological tissue sealing material of Example 1 of the present invention;

[0024] Figure 8 This is a photo of the hemostatic performance test of the biological tissue sealing material of Example 1 of the present invention;

[0025] Fig. 9 is a photograph of the adhesion strength test of the biological tissue sealing material of Example 1 of the present invention in different organs;

[0026] Fig.10 is a photograph of the adhesion strength test process of the biological tissue sealing material of Example 1 of the present invention on the muscle surface;

[0027] Fig.11 This is a photograph of the adhesion strength test result of the biological tissue sealing material of Example 1 of the present invention on the muscle surface. DETAILED DESCRIPTION

[0028] The biological tissue sealing material and the preparation method thereof of the present invention are described below with reference to the examples. In the following examples, the reagents and materials whose sources are not specified are all commercially available, and the operation methods without specific processes are referred to the conventional operation methods in the prior art.

[0029] In the following examples, aldehyde-modified natural polysaccharides are used, specifically aldehyde-modified dextran, aldehyde-modified hyaluronic acid and aldehyde-modified pullulan; sodium periodate is used in the aldehyde-modification reaction of the three. In addition, the molecular weights of dextran, hyaluronic acid and Prussian blue in the present invention are 10,000 to 150,000, and the molecular weights used in the examples are all about 100,000.

[0030] The specific aldehyde formation method is as follows:

[0031] Aldehyde dextran: Dissolve 5 g of dextran in 100 mL of pure water and stir until the dextran is completely dissolved. Weigh 10 g of sodium periodate and add it to a spherical bottle, stir and react overnight. Then, place the solution in a 3 L beaker and dialyze it with pure water for 3 days to remove small molecular byproducts, and freeze-dry the dialyzed solution to obtain aldehyde dextran.

[0032] Aldehydation of hyaluronic acid: Dissolve 5 g of hyaluronic acid in 100 mL of pure water and stir until the hyaluronic acid is completely dissolved. Weigh 10 g of sodium periodate and add it to a spherical bottle, stir and react overnight. Then, place the solution in a 3 L beaker and dialyze it with pure water for 3 days to remove small molecule byproducts, and freeze-dry the dialyzed solution to obtain aldehydation of hyaluronic acid.

[0033] Aldehyde pullulan: Dissolve 2g hyaluronic acid in 100mL pure water and stir until the hyaluronic acid is completely dissolved. Weigh 5g sodium periodate and add it to a spherical bottle, stir and react overnight. Then, place the solution in a 3L beaker and dialyze it with pure water for 3 days to remove small molecule byproducts, and freeze-dry the dialyzed solution to obtain aldehyde pullulan.

[0034] <Example 1>

[0035] The preparation method of the biological tissue sealing material of this embodiment comprises the following steps:

[0036] Step S1, re-dissolving the prepared aldehyde dextran in water to prepare an aldehyde dextran solution with a concentration of 10%, and adjusting the pH to 8.5 with NaOH;

[0037] Step S2, directly placing the solution prepared in step S1 into a freeze dryer precooled to -40°C for 8 hours;

[0038] Step S3, setting the vacuum degree of the freeze dryer to 0.5 mbar, and freeze drying for 48 hours;

[0039] Step S4, maintaining a vacuum degree of 0.5 mbar, heating to 0°C at a rate of 10°C / hour, and freeze-drying for 12 hours;

[0040] Step S5, returning the vacuum degree to normal pressure, raising the temperature to 50°C at a rate of 10°C / hour, and maintaining the temperature for 12 hours to obtain a biological tissue sealing material of aldehyde-dextran.

[0041] Figure 1 is a physical photograph of the biological tissue sealing material of Example 1 of the present invention, Figure 2 This is an electron microscope photograph of the biological tissue sealing material of Example 1 of the present invention.

[0042] like Figure 1 As shown, the biological tissue sealing material of Example 1 is sponge-like, with a dense surface, and a very dense structure at the cross section when torn open, without obvious pores visible to the naked eye.

[0043] like Figure 2 As shown, in the microstructure of the biological tissue sealing material of Example 1, the pore structure is mostly closed pores, which are closely arranged with each other, and the pores are all smaller than 10 μm, indicating that the internal structure of the biological tissue sealing material is also very dense.

[0044] <Example 2>

[0045] The preparation method of the biological tissue sealing material of this embodiment comprises the following steps:

[0046] Step S1, re-dissolving the prepared aldehyde-modified hyaluronic acid in water to prepare a aldehyde-modified hyaluronic acid solution with a concentration of 3%, and adjusting the pH to 7 with NaOH;

[0047] Step S2, directly placing the solution prepared in step S1 into a freeze dryer precooled to -80°C for 3 hours;

[0048] Step S3, setting the vacuum degree of the freeze dryer to 0.01 mbar, and freeze drying for 72 hours;

[0049] Step S4, maintaining a vacuum degree of 0.01 mbar, heating to 0°C at a rate of 15°C / hour, and freeze-drying for 12 hours;

[0050] Step S5, returning the vacuum degree to normal pressure, raising the temperature to 40°C at a rate of 20°C / hour, and maintaining the temperature for 24 hours to obtain a biological tissue sealing material of aldehyde-modified hyaluronic acid.

[0051] Similar to Example 1, the biological tissue sealing material of this example is also sponge-like, with a dense surface, and a very dense structure at the cross section that can be seen when torn open, without obvious pores visible to the naked eye.

[0052] <Example 3>

[0053] The preparation method of the biological tissue sealing material of this embodiment comprises the following steps:

[0054] Step S1, re-dissolving the prepared aldehyded pullulan in water to prepare an aldehyded pullulan solution with a concentration of 0.5%, and adjusting the pH to 9 with NaOH;

[0055] Step S2, directly placing the solution prepared in step S1 into a freeze dryer precooled to -50°C for 12 hours;

[0056] Step S3, setting the vacuum degree of the freeze dryer to 0.1 mbar, and freeze drying for 96 hours;

[0057] Step S4, maintaining a vacuum degree of 0.1 mbar, heating to 0°C at a rate of 5°C / hour, and then freeze-drying for 24 hours;

[0058] Step S5, returning the vacuum degree to normal pressure, raising the temperature to 30°C at a rate of 15°C / hour, and maintaining the temperature for 18 hours to obtain an aldehyded pullulan biological tissue sealing material.

[0059] Similar to Example 1 and Example 2, the biological tissue sealing material of this example is also sponge-like, with a dense surface, and a very dense structure at the cross section when torn open, without obvious pores visible to the naked eye.

[0060] <Comparative Example 1>

[0061] This comparative example provides another material prepared from aldehyde-modified dextran, and its preparation method is as follows:

[0062] The prepared aldehyde dextran was redissolved in water to prepare an aldehyde dextran solution with a concentration of 10%; the prepared solution was directly placed in a freeze dryer precooled to -40°C for 8 hours; then, the vacuum degree was set to 0.5 mbar and freeze-dried for 48 hours to obtain the product.

[0063] Figure 3 is a physical photograph of the aldehyde-deoxyglucan material of Comparative Example 1 of the present invention, Figure 4 It is an electron microscope photograph of the aldehyde-deoxyglucan material of Comparative Example 1 of the present invention.

[0064] like Figure 3 As shown, the aldehyde-deoxyglucan material obtained in Comparative Example 1 has obvious pores visible to the naked eye and obvious cracks on its surface.

[0065] like Figure 4 As shown, in the aldehyde-deoxyglucan material of Comparative Example 1, the pore structure is mostly open pores, which are arranged loosely and irregularly, and the pores are all larger than 50 μm.

[0066] <Comparative Example 2>

[0067] This comparative example provides another material prepared from aldehyde-modified hyaluronic acid, and its preparation method is as follows:

[0068] The prepared aldehyde-modified hyaluronic acid was redissolved in water to prepare a aldehyde-modified hyaluronic acid solution with a concentration of 3%; the prepared solution was directly placed in a freeze dryer precooled to -60°C for 3 hours; then, the vacuum degree was set to 0.01 mbar and freeze-dried for 72 hours to obtain the solution.

[0069] The aldehyde-modified hyaluronic acid material obtained in this comparative example is similar to that in comparative example 1, and has obvious pores visible to the naked eye and obvious cracks on the surface.

[0070] <Comparative Example 3>

[0071] This comparative example provides another material prepared from aldehyde-formyl pullulan, and its preparation method is as follows:

[0072] The prepared aldehyded pullulan was redissolved in water to prepare an aldehyded pullulan solution with a concentration of 0.5%; the prepared solution was directly placed in a freeze dryer precooled to -50°C and kept for 12 hours; then, the vacuum degree was set to 0.1 mbar and freeze-dried for 92 hours to obtain the product.

[0073] The aldehyde-formyl pullulan material obtained in this comparative example is similar to that of comparative examples 1 and 2, and both have obvious pores visible to the naked eye and obvious cracks on the surface.

[0074] <Test Example 1>

[0075] This test example is a cross-linking test of the materials obtained in Example 1 and Comparative Example 1.

[0076] The specific test method is: take 0.05g of the materials of Example 1 and Control Example 1, and soak them in 1.5ml of pure water and 10% polylysine solution respectively for 30 minutes.

[0077] Figure 5 This is a photo of the biological tissue sealing material of Example 1 of the present invention after being immersed in pure water and polylysine solution for 30 minutes, wherein the left side is pure water and the right side is polylysine solution.

[0078] It was observed that the biological tissue sealing material in Example 1 could be completely dissolved in water within 20 minutes, but would not be dissolved in a 10% polylysine solution. Figure 5 As shown, after immersion for 30 minutes, the material in the pure water has dissolved and is uniform overall, while a gel-like object (within the dotted box in the figure) remains in the polylysine solution.

[0079] The reason why the biological tissue sealing material is insoluble in the polylysine solution is that the aldehyde groups in the material chemically react with the amino groups and / or thiol groups on the polylysine, thereby causing the biological tissue sealing material to be cross-linked.

[0080] In addition, it was observed that the aldehyde-deoxyglucan material of Control Example 1 could be completely dissolved in water within 5 minutes, but would also cross-link into a gel in a 10% polylysine solution and would not dissolve.

[0081] The sample soaked in the polylysine solution for 30 minutes was taken out for weighing test, and the water absorption per gram of the material was calculated by comparing the total weight difference before and after soaking. The water absorption of the material in Example 1 was 1.1 g / g, and the water absorption of the material in Control Example 1 was 26 g / g.

[0082] <Test Example 2>

[0083] This test example is a cross-linking water absorption test of the materials obtained in each embodiment and comparative example.

[0084] The specific test method is: take 0.05g of biological tissue sealing material, soak it in an excess of 10% polylysine solution, take it out and weigh it after 24 hours, and calculate the water absorption per gram of material based on the total weight difference before and after soaking. The results are as follows:

[0085] Table 1 Water absorption of biological tissue sealing materials of Examples and Comparative Examples

[0086] Group Water absorption (g / g) Example 1 1.2 Example 2 3.1 Example 3 1.8 Comparative Example 1 54 Comparative Example 2 77 Comparative Example 3 36

[0087] It can be seen that the water absorption of the biological tissue sealing materials of Examples 1 to 3 is relatively low, with the water absorption per gram of material being 1.2 to 3.1 g, that is, the water absorption of the biological tissue sealing materials of the examples is about 1 to 3 times of their own weight.

[0088] In comparison, the water absorption of the three aldehyde-modified polysaccharide materials in Comparative Examples 1 to 3 is very high, ranging from 36 to 77 g per gram of material; that is, the water absorption of the materials in the comparative examples is more than 30 times of their own weight, which is also the water absorption range of common hemostatic biomaterials such as gelatin sponges.

[0089] <Test Example 3>

[0090] This test example is a test of the hemostatic performance of the materials obtained in Example 1 and Comparative Example 1.

[0091] The specific test method is: to conduct a hemostatic performance test in a femoral artery transection massive bleeding model of a New Zealand white rabbit weighing 2.5kg. After the rabbit is anesthetized, a 1 cm incision is made at the rabbit's femoral artery with a scalpel to cut the femoral artery; then, 0.2g of the prepared material is quickly pressed on the bleeding wound, the pressure is maintained for a certain period of time, and then released.

[0092] Figure 6 The photographs are of the hemostatic performance test of the biological tissue sealing material of Example 1 of the present invention. The left side shows the state of the femoral artery just cut open, and the right side shows the state of the biological tissue sealing material being released after being pressed for 30 seconds.

[0093] like Figure 6 As shown, after the femoral artery was cut, a large amount of blood was seen gushing out rapidly; the biological tissue sealing material was quickly pressed on the bleeding wound and pressed, and after releasing it, it was seen that no more blood flowed out of the femoral artery incision, and the surface of the biological tissue sealing material was not stained red by the blood, proving that the sponge-like aldehyde-deoxyglucan biological tissue sealing material obtained in Example 1 has excellent tissue adhesion and sealing properties.

[0094] Figure 7 This is a photo of the hemostatic performance test of the aldehyde-dextran material of comparative example 1 of the present invention. The left side shows the state of the femoral artery just cut open, and the right side shows the state of the artery being released after being pressed for 3 minutes.

[0095] like Figure 7 As shown, after the femoral artery was cut, a large amount of blood was seen gushing out rapidly; the aldehyde-dextran material was quickly pressed on the bleeding wound for 3 minutes, and after it was released, it was seen that the material was completely dyed red by the blood and swelled by the blood, and the blood quickly gushed out from under the material and on the surface of the material after the pressure was released, indicating that the material obtained in Control Example 1 could not block the massive bleeding of the femoral artery of the main rabbit and could not achieve rapid hemostasis.

[0096] <Test Example 4>

[0097] This test example is a lymphatic leakage blocking test of the materials obtained in Example 2 and Comparative Example 2.

[0098] The specific test method is: after the rabbit is anesthetized, find the rabbit's lymphatic vessel and make a 2mm diameter incision, with white milky liquid flowing out; press 0.2g of biological tissue sealing material on the incision, keep pressing for a certain period of time, then release it and observe the wound condition. Then, suture the wound and place a drainage tube, and observe the liquid drainage within 3 days.

[0099] After testing and observation, 0.2g of the biological tissue sealing material of Example 2 was pressed on the notch and kept pressed for 15 minutes before being released. After continued observation, no liquid flowed out within 15 minutes. After suturing and placing a drainage tube, basically no liquid was drained out within 3 days, indicating that the biological tissue sealing material obtained in Example 2 has excellent tissue adhesion and sealing performance.

[0100] In addition, 0.2 g of the aldehyde-modified hyaluronic acid material of Comparative Example 2 was pressed on the notch and kept pressed for 15 minutes before being released. After continued observation, it was seen that the material obviously absorbed water and swelled, and white chyle-like liquid slowly flowed out. After suturing and placing a drainage tube, obvious white chyle-like liquid was drained out in the first two days, indicating that the tissue adhesion and sealing performance of the material obtained in Comparative Example 2 was limited.

[0101] <Test Example 5>

[0102] This test example is a test of the hemostatic performance of the material obtained in Example 1.

[0103] The specific test method is: to conduct a massive bleeding hemostasis performance test in a femoral artery injury bleeding model of a Bama miniature pig weighing 40 kg. After the pig is anesthetized, a 0.5 cm incision is made at the femoral artery with a scalpel; then, the prepared material with an area of ​​2 cm*2 cm is quickly pressed on the bleeding wound, the pressure is maintained for a certain period of time, and then released.

[0104] Figure 8 This is a photo of the hemostatic performance test of the biological tissue sealing material of Example 1 of the present invention. The upper side shows the state just after the incision, and the lower side shows the state of the biological tissue sealing material being released after being pressed for 30 seconds.

[0105] like Figure 8 As shown, after cutting, a clear wound end surface can be seen (the part indicated by the arrow in the photo), and a large amount of blood is ejected; the biological tissue sealing material is quickly pressed on the wound and pressed continuously. After releasing it, it can be seen that no blood flows out of the femoral artery incision, and the surface of the biological tissue sealing material is not stained red by blood, which proves that the sponge-like aldehyde dextran biological tissue sealing material obtained in Example 1 has excellent tissue adhesion and sealing properties.

[0106] <Test Example 6>

[0107] This test example is an adhesion strength test of the material obtained in Example 1.

[0108] The test method is: select fresh rat organs (including heart, liver, spleen, lung, kidney, stomach, small intestine and tail) that have not been wiped of blood or tissue fluid, and immediately press a biological tissue sealing material of about 1cm×1cm size quickly on the surface of the organ and continue pressing for 30s. After releasing it, use tweezers to clamp the biological tissue sealing material and lift it up.

[0109] Fig. 9 These are test photos of the adhesion strength of the biological tissue sealing material of Example 1 of the present invention in different organs.

[0110] like Fig. 9 As shown, the biological tissue sealing material of the present invention can adhere to the fresh tissue surfaces of various organs such as the heart, liver, spleen, lung, kidney, stomach, small intestine and tail, and even if the material is clamped to lift the entire organ, there is no material falling off or tearing. On the one hand, it shows that the biological tissue sealing material has good tissue adhesion performance and high mechanical strength. On the other hand, it also shows that the biological tissue sealing material is suitable for the surfaces of various organs.

[0111] <Test Example 7>

[0112] This test example is an adhesion strength test of the material obtained in Example 1.

[0113] The test method is: after removing the skin on the back of the rat to expose the muscle surface, immediately press the biological tissue sealing material of about 1.5cm×4cm on the muscle surface quickly and continuously for 30s, then use tweezers to clamp the biological tissue sealing material and lift the rat as a whole. Then, use tweezers to tear the sealing material open with force, and take photos to record the whole tearing process.

[0114] Fig.10 This is a photograph of a rat being lifted in a test of the adhesion strength of the biological tissue sealing material of Example 1 of the present invention on the muscle surface, wherein the upper side is a state when not lifted, and the lower side is a state when lifted; Fig.10 These are photos of the material tearing process of the adhesion strength test of the biological tissue sealing material of Example 1 of the present invention on the muscle surface, wherein the photos are arranged from left to right in chronological order.

[0115] like Fig.10As shown, after the biological tissue sealing material of the present invention is applied to the surface of fresh muscle tissue, it adheres to the muscle tissue. Even when a rat weighing 486 g is lifted, there is no phenomenon of material falling off or tearing, which indicates that the biological tissue sealing material has good tissue adhesion performance and high mechanical strength.

[0116] like Fig.11 As shown, after the biological tissue sealing material of the present invention is applied to the surface of fresh muscle tissue, it can quickly combine with the amino groups on the tissue surface to form strong adhesion. After tearing the sealing material open with tweezers, it can be seen that there is still a layer of material bonded to the tissue surface, indicating that the biological tissue sealing material has good tissue adhesion performance and high mechanical strength.

[0117] Functions and Effects of the Embodiments

[0118] As described above, in Examples 1 to 3, since the aldehyde-modified polysaccharide is freeze-dried by a segmented method, that is, after being placed in a pre-freeze dryer, it is first kept at a low temperature for a period of time and then vacuumed for the first freeze-drying process, and then the vacuum is maintained and the temperature is slowly raised for the second freeze-drying process, and finally the normal pressure is restored and the temperature is raised and maintained, the biological tissue sealing material finally obtained can present a dense structure and small pores; such a biological tissue sealing material itself is easily soluble in water, but it is not easy to absorb water and swell. When used, once it contacts the body fluid or tissue surface, it can react and cross-link with the amino / thiol group on the cell or protein in the body fluid or tissue surface to form a physical sealing layer, thereby effectively sealing the wound site. In addition, the biological tissue sealing material also has good tissue adhesion properties and high mechanical strength, and can be applied to the surfaces of various organs.

[0119] In comparison, the aldehyde-modified polysaccharide materials of Examples 1 to 3 prepared by traditional freeze-drying methods have relatively loose structures and large pores, and their water absorption capacity is very high, which causes them to swell easily after contacting body fluids or tissues. This swelling will cause the material to deform, and the pores will further increase, making it difficult to effectively seal the wound site.

Claims

1. A biological tissue sealing material, It is characterized in that The biological tissue sealing material is in a sponge shape and is prepared from an aldehyde-modified natural polysaccharide solution by segmented freeze-drying. The water absorption of the biological tissue sealing material is less than 5g / g.

2. The biological tissue sealing material according to claim 1, characterized in that: in, The aldehyde-modified natural polysaccharide is a combination of one or more of aldehyde-modified hyaluronic acid, aldehyde-modified dextran, aldehyde-modified pullulan, aldehyde-modified chitosan and aldehyde-modified carboxymethyl cellulose.

3. The biological tissue sealing material according to claim 1, characterized in that: in, The biological tissue sealing material is not easy to absorb water and swell, and when used, it reacts and cross-links with the amino / thiol groups on cells or proteins in body fluids or tissue surfaces to form a physical sealing layer, thereby sealing the wound site.

4. The biological tissue sealing material according to claim 1, characterized in that: in, The pores in the biological tissue sealing material are 1 to 40 μm.

5. The biological tissue sealing material according to claim 4, characterized in that: in, The pores in the biological tissue sealing material are 10 to 20 μm.

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