A polyvinyl alcohol sponge, its preparation method and application

Abstract

This invention discloses a polyvinyl alcohol (PVA) sponge, its preparation method, and its applications. The PVA sponge comprises a PVA sponge matrix and a layer of polyphenolic compounds on its surface, wherein a polymer with hemostatic properties is grafted onto the surface of the PVA sponge matrix via polyphenolic compounds. This invention utilizes PVA sponge and the biomimetic principle of mussels to construct a secondary reaction platform on the sponge through the strong adhesive effect of polyphenolic compounds. Then, through Schiff base reaction and free radical polymerization, natural polymers with hemostatic properties are grafted onto the sponge, resulting in a PVA hemostatic sponge with excellent hemostatic and mechanical properties for battlefield wound first aid.

Description

Technical Field

[0001] This invention relates to the field of polymer materials, specifically to a polyvinyl alcohol (PVA) sponge, its preparation method, and its application in hemostatic materials. The PVA sponge is prepared by using PVA medical sponge to build a secondary reaction platform through the strong bonding effect of polyphenolic compounds, followed by loading natural hemostatic polymers through Schiff base reaction and free radical polymerization. Background Technology

[0002] Whether in combat or peacetime trauma, uncontrollable bleeding from large blood vessels and widespread oozing from wounded tissues are major causes of death among wounded soldiers. Statistics show that massive bleeding leads to 43% of deaths after trauma in everyday life, while the mortality rate on the battlefield reaches as high as 90%. Timely and effective first aid and hemostasis can buy valuable time for the evacuation of wounded soldiers, reducing mortality and disability rates.

[0003] Polyvinyl alcohol (PVA) is widely used in the field of biomedical materials due to its good hydrophilicity and biocompatibility. PVA compression sponges have excellent liquid absorption and swelling properties, making them a commonly used hemostatic material in clinical practice. However, PVA sponges themselves do not possess clotting ability; even if they can rapidly absorb blood flowing from a wound, they cannot quickly promote thrombus formation, thus failing to achieve effective hemostasis for massive bleeding wounds.

[0004] Natural polymers are widely used in military and civilian hemostatic products due to their wide availability, good biocompatibility, and hemostatic properties. For example, chitosan, due to its positive charge, can directly adsorb red blood cells, causing them to adhere. Simultaneously, chitosan can promote fibrinogen adhesion, accelerating the formation of large blood clots. The negatively charged carboxyl groups on the cellulose molecular chain can combine with ferrous ions in hemoglobin to form brown gel-like masses, sealing the capillary ends and thus achieving hemostasis. Collagen can activate the activity of some blood clotting factors, guiding platelet adhesion.

[0005] Patent CN115300665 A invented an antibacterial absorbable nasal hemostatic sponge, which is prepared by mixing an aqueous solution of antibacterial agent, quaternized gelatin, chitosan, polyvinyl alcohol, and sodium alginate, adding genipin crosslinking agent, adding polylactic acid microspheres, and freeze-drying. Patent CN 113134112 A disclosed a rapid liquid absorption and expansion type composite compression hemostatic sponge and its preparation method, which is prepared by dissolving, crosslinking, pore forming and freeze-drying polyvinyl alcohol and chitosan. The sponge prepared by this method has chitosan evenly distributed on the surface and inside of the hemostatic sponge particles, thereby enhancing the hemostatic performance. Patent CN 101342381 A fixes chitosan gel microspheres on the inner wall of the sponge by crosslinking polyvinyl alcohol to obtain a PVA / chitosan hemostatic sponge.

[0006] The above methods all involve adding hemostatic functional components during the preparation of polyvinyl alcohol sponge, which may affect the structure of the polyvinyl alcohol sponge itself and reduce its structural integrity and mechanical properties. Summary of the Invention

[0007] To address the problems existing in the prior art, this invention provides a polyvinyl alcohol sponge, its preparation method, and its application. This invention uses commercially available medical-grade polyvinyl alcohol sponge and, utilizing the biomimetic principle of mussels, constructs a secondary reaction platform on the sponge through the strong adhesive effect of polyphenolic compounds. Then, through Schiff base reaction and free radical polymerization, natural polymers with hemostatic properties are grafted onto the sponge, resulting in a polyvinyl alcohol hemostatic sponge for battlefield wound first aid with excellent hemostatic and mechanical properties.

[0008] One objective of this invention is to provide a polyvinyl alcohol sponge, comprising a polyvinyl alcohol sponge matrix and a polyphenolic compound layer on its surface, wherein a polymer with coagulation function is grafted onto the surface of the polyvinyl alcohol sponge matrix through the polyphenolic compound.

[0009] In this invention, polyphenolic compounds such as polydopamine, polytannic acid, or polygallic acid are deposited and adhered to the inner and outer surfaces of polyvinyl alcohol sponge to form a coating.

[0010] The coagulation-functional polymers include natural polymers with amino groups and natural polymers with double bond functionalization.

[0011] The amino-containing natural polymer is selected from at least one of chitosan or its derivatives and gelatin; the double-bond functionalized natural polymer is selected from at least one of the following double-bond functionalized natural polymers: chitosan or its derivatives, cellulose or its derivatives, gelatin, and alginate.

[0012] The double bond is functionalized into methacrylamide.

[0013] The polyphenolic compounds are selected from at least one of dopamine, tannic acid, or gallic acid.

[0014] Polyvinyl alcohol sponge can be made from medical-grade PVA sponge.

[0015] The polyvinyl alcohol hemostatic sponge uses commercial medical-grade polyvinyl alcohol sponge as a base, is connected by polyphenolic compounds, and is loaded with natural polymers with hemostatic function on the surface and inside.

[0016] The shape of a sponge varies depending on the application, including but not limited to sheet-like, cylindrical, cube-shaped, cubic, and other suitable shapes of different sizes.

[0017] The second objective of this invention is to provide a method for preparing the polyvinyl alcohol sponge described above, comprising forming a polyphenolic compound layer on a polyvinyl alcohol sponge matrix, then loading polymer A through a Schiff base reaction, and finally adding double-bond functionalized polymer B for free radical polymerization.

[0018] According to a preferred embodiment of the present invention, the preparation method includes:

[0019] (1) Polyphenolic compounds are used to modify the polyvinyl alcohol sponge matrix to form a polyphenolic compound layer on the surface of the polyvinyl alcohol sponge matrix;

[0020] (2) Immerse the modified polyvinyl alcohol sponge in a solution of polymer A;

[0021] (3) The polyvinyl alcohol sponge obtained in step (2) is then immersed in a solution of double bond functionalized polymer B, and a free radical initiator is added to carry out the reaction to obtain the polyvinyl alcohol sponge.

[0022] Based on the above technical solution, the polymer A is selected from at least one of chitosan or its derivatives, gelatin, double-bond functionalized chitosan or its derivatives, and double-bond functionalized gelatin. The polymer A contains amino groups, which can undergo a Schiff base reaction. For example, it can use chitosan, alkylated chitosan, carboxymethyl chitosan, gelatin, double-bond functionalized chitosan or its derivatives, or double-bond functionalized gelatin such as methacryloxychitosan or methacryloxygelatin. Preferably, it is a mixture of at least one of chitosan or its derivatives, gelatin, and at least one of double-bond functionalized chitosan or its derivatives, and double-bond functionalized gelatin.

[0023] Based on the above technical solution, the polymer B is selected from at least one of the following double-bond functionalized natural polymers: chitosan or its derivatives, cellulose or its derivatives, gelatin, alginate, including but not limited to methacrylated chitosan, methacrylated carboxymethyl cellulose, methacrylated gelatin, methacrylated sodium alginate, etc.

[0024] Based on the above technical solutions, double-bond functionalized natural polymers can be prepared using methods commonly used in the field.

[0025] Based on the above technical solution, the preferred method for double bond functionalization is methacrylylation.

[0026] Based on the above technical solution, step (1) includes: immersing the polyvinyl alcohol sponge matrix in a polyphenol compound solution, sonicating for 10 to 30 minutes, and then stirring at 10 to 30°C for 8 to 48 hours.

[0027] Based on the above technical solution, in step (1), the polyphenolic compound can be selected from at least one of dopamine, dopamine hydrochloride, tannic acid or gallic acid.

[0028] Based on the above technical solution, in step (1), the mass concentration of the polyphenol compound solution is 0.2% to 5%, preferably 0.5% to 3%.

[0029] Based on the above technical solution, in step (1), the pH of the polyphenol compound solution is 8 to 10.

[0030] Based on the above technical solution, according to a preferred embodiment, dopamine hydrochloride is dissolved in tris(hydroxymethyl)aminomethane buffer solution, the pH of the dopamine hydrochloride solution is adjusted to 8-10, and the solution is sonicated until the solid is completely dissolved.

[0031] Based on the above technical solution, in step (1), after the reaction is completed, the modified polyvinyl alcohol sponge is taken out and repeatedly rinsed with distilled water, and then dried for later use.

[0032] Based on the above technical solution, in step (2), the pH of the solution of polymer A is 8 to 10.

[0033] Based on the above technical solution, in step (2), the mass concentration of the polymer A solution is 1% to 20%, preferably 4% to 10%.

[0034] Based on the above technical solution, in step (2), the solution of polymer A is an aqueous solution of natural polymer A.

[0035] Based on the above technical solution, in step (2), the soaking time is 10-16 hours and the soaking temperature is 10-30°C.

[0036] Based on the above technical solution, in step (3), the mass concentration of the solution of double bond functionalized polymer B is 1% to 20%, preferably 4% to 10%.

[0037] Based on the above technical solution, in step (3), the solution of double-bond functionalized polymer B is an aqueous solution of double-bond functionalized natural polymer B.

[0038] Based on the above technical solution, in step (3), the free radical initiator is a water-soluble azo initiator and / or a redox initiator. Preferably, the azo initiator is selected from at least one of 2,2-azobisisobutyrate, 2,2'-azo[2-(2-imidazolinyl)propane] dihydrochloride, and azobisisobutyramidine hydrochloride. The redox initiator includes an oxidant and a reducing agent. The oxidant is selected from at least one of potassium persulfate, sodium persulfate, and hydrogen peroxide. The reducing agent is selected from at least one of sodium thiosulfate, ferrous chloride, and ascorbic acid.

[0039] Based on the above technical solution, in step (3), the amount of the free radical initiator is 0.2% to 1.5% of the total mass of the double bond functionalized polymer B.

[0040] Based on the above technical solution, in step (3), the reaction time is 4 to 8 hours and the reaction temperature is 20 to 80 degrees Celsius.

[0041] Based on the above technical solution, step (3) may further include cleaning the obtained polyvinyl alcohol sponge, such as soaking it in distilled water and anhydrous ethanol, and drying it. The polyvinyl alcohol sponge can be compressed using specific equipment and then sterilized with ethylene oxide and sealed for storage.

[0042] The third objective of this invention is to provide the application of the polyvinyl alcohol sponge described above or the polyvinyl alcohol sponge prepared by the above method in hemostatic materials.

[0043] The beneficial effects of this invention are:

[0044] (1) Polyphenolic compounds can adhere firmly to the sponge substrate through oxidative self-polymerization, forming a polyphenolic compound coating. Polyphenolic compounds such as polydopamine contain a large number of active functional groups such as amino, imino, and catechol in their molecular structure, which build a secondary reaction platform while maintaining the structural integrity of the polyvinyl alcohol sponge.

[0045] (2) Polyphenolic compounds, such as polydopamine, have a large number of catechol groups in their molecular structure. Under alkaline conditions, these groups are converted into quinone groups, which can undergo a Schiff base reaction with the amino-NH2 groups on natural polymers. This allows the natural polymers to be covalently grafted onto the surface and interior of polyvinyl alcohol sponges. When treating massive bleeding from combat wounds, the coagulation-functional natural polymers loaded on the sponge will not be washed away by the blood flow and will not lose their coagulation function.

[0046] (3) Because the amino groups on the molecular structure of natural polymers react with polyphenols, some functional groups with coagulation function will be consumed. Therefore, by loading natural polymers with double bonds and then attaching more natural polymers through free radical polymerization, the coagulation function of the material can be further enhanced.

[0047] (4) Since it is based on commercial polyvinyl alcohol sponge, the final hemostatic material can be made into different forms of use according to the needs of different application scenarios without being affected by the modification process. Detailed Implementation

[0048] The present invention will now be described in detail with reference to specific embodiments. It should be noted that the following embodiments are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the content of the present invention are still within the scope of protection of the present invention.

[0049] Furthermore, various embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention. The resulting technical solutions are part of the original disclosure of this specification and also fall within the protection scope of the present invention.

[0050] Unless otherwise specified, the raw materials used in the examples and comparative examples are all disclosed in the prior art, such as those that can be directly purchased or prepared according to the preparation methods disclosed in the prior art.

[0051] According to a preferred embodiment of the present invention, the preparation method includes:

[0052] Step 1: Cut the purchased medical-grade polyvinyl alcohol sponge into appropriate sizes, ultrasonically clean it three times with anhydrous ethanol or acetone, and dry it for later use.

[0053] Step 2: Weigh a certain amount of dopamine hydrochloride and dissolve it in a certain amount of tris(hydroxymethyl)aminomethane buffer solution, adjust the pH to 8-10, and sonicate until the solid is completely dissolved.

[0054] Step 3: Immerse the polyvinyl alcohol sponge treated in Step 1 completely in the hydrochloric acid dopamine solution prepared in Step 2, sonicate for 10 to 30 minutes, and stir at room temperature (e.g., 25°C) for 8 to 48 hours.

[0055] Step 4: After the reaction is complete, remove the sponge and rinse it repeatedly with distilled water, then dry it for later use.

[0056] Step 5: Prepare an aqueous solution of natural polymer A with a certain concentration of hemostatic function, adjust the pH of the solution to 8-10 with an alkaline substance, immerse the dopamine-modified polyvinyl alcohol sponge, and stir at room temperature (e.g., 25°C) for 10-16 hours.

[0057] Step 6: Soak and rinse the modified sponge repeatedly with distilled water, then immerse the sponge in an aqueous solution of a certain concentration of double-bond functionalized natural polymer B with coagulation function. Add a free radical initiator under a nitrogen atmosphere and react at 20-80℃ for 4-8 hours.

[0058] Step 7: After the reaction is complete, remove the sponge and repeatedly soak and wash it with distilled water and anhydrous ethanol. After drying, you will obtain a polyvinyl alcohol hemostatic sponge for combat wound first aid. This hemostatic sponge can be compressed using specific equipment and then sterilized with ethylene oxide and sealed for storage.

[0059] Double-bond functionalized natural polymers can be prepared using methods commonly used in the field, taking methacrylamide gelatin as an example:

[0060] A certain amount of gelatin and deionized water were placed in a flask and heated and stirred until dissolved. The pH of the gelatin solution was adjusted to about 8 using 1M NaOH solution. Then, under nitrogen protection, excess methacrylic anhydride was added, and the mixture was reacted at 50°C with stirring for 2–3 hours. The resulting mixture was cooled to room temperature and dialyzed against deionized water for 3 days, changing the water twice a day. Finally, it was freeze-dried to obtain double-bonded gelatin, i.e., methacrylamide gelatin.

[0061] Based on the above technical solution, in step 3, the ratio of polyvinyl alcohol sponge to dopamine hydrochloride solution is such that the sponge can be completely immersed in the solution.

[0062] Based on the above technical solution, the alkaline substance in step 5 is sodium hydroxide, potassium hydroxide, or tris(hydroxymethyl)aminomethane buffer solution.

[0063] Example 1

[0064] Operating steps:

[0065] Step 1: Cut the purchased medical-grade polyvinyl alcohol sponge into 1cm pieces. 3 The small cubes were ultrasonically cleaned three times with anhydrous ethanol and then dried for later use.

[0066] Step 2: Weigh 0.16g of dopamine hydrochloride and dissolve it in 30ml of tris(hydroxymethyl)aminomethane buffer solution with a pH of 8.5, and sonicate until the solid is completely dissolved;

[0067] Step 3: Immerse the polyvinyl alcohol sponge treated in Step 1 completely in the hydrochloric acid dopamine solution prepared in Step 2, sonicate for 10-30 minutes, and stir at room temperature (25°C) for 40 hours.

[0068] Step 4: After the reaction is complete, remove the sponge and rinse it repeatedly with distilled water, then dry it for later use.

[0069] Step 5: Add carboxymethyl chitosan and methacrylamide gelatin to distilled water and stir until completely dissolved, so that the mass concentrations of carboxymethyl chitosan and methacrylamide gelatin are 4% and 3% respectively. Adjust the pH of the solution to 8.5 with sodium hydroxide, immerse the dopamine-modified polyvinyl alcohol sponge, and stir at room temperature (25°C) for 16 hours.

[0070] Step 6: Rinse the modified sponge repeatedly with distilled water, then immerse the sponge in 30 ml of 8% aqueous solution of methacryloyl carboxymethyl chitosan. Under a nitrogen atmosphere, add 0.02 g of potassium persulfate / ascorbic acid (mass ratio 2:1) and react at 40 °C for 8 h.

[0071] Step 7: After the reaction is complete, remove the sponge and repeatedly soak and wash it with distilled water and anhydrous ethanol. After drying, you will obtain a polyvinyl alcohol hemostatic sponge for combat wound first aid. This hemostatic sponge can be compressed using specific equipment and then sterilized with ethylene oxide and sealed for storage.

[0072] Example 2

[0073] Operating steps:

[0074] Step 1: Cut the purchased medical-grade polyvinyl alcohol sponge into 5×5cm pieces. 2 The thin slices, 2mm thick, were ultrasonically cleaned three times with acetone and then dried for later use.

[0075] Step 2: Weigh 0.2g of dopamine hydrochloride and dissolve it in 20ml of tris(hydroxymethyl)aminomethane buffer solution with a pH of 9.0, and sonicate until the solid is completely dissolved;

[0076] Step 3: Immerse the polyvinyl alcohol sponge treated in Step 1 completely in the hydrochloric acid dopamine solution prepared in Step 2, sonicate for 10-30 minutes, and stir at room temperature (25°C) for 30 hours.

[0077] Step 4: After the reaction is complete, remove the sponge and rinse it repeatedly with distilled water, then dry it for later use.

[0078] Step 5: Add gelatin and methacrylamide chitosan to distilled water and stir until completely dissolved, so that the mass concentrations of gelatin and methacrylamide chitosan are 2% and 4% respectively. Adjust the pH of the solution to 9.0 with potassium hydroxide, immerse the dopamine-modified polyvinyl alcohol sponge, and stir at room temperature (25°C) for 12 hours.

[0079] Step 6: Rinse the modified sponge repeatedly with distilled water, then immerse the sponge in 40 ml of 6% aqueous solution of methacryloyl carboxymethyl cellulose. Under a nitrogen atmosphere, add 0.024 g of dimethyl 2,2-azobisisobutyrate and react at 45 °C for 6 h.

[0080] Step 7: After the reaction is complete, remove the sponge and repeatedly soak and wash it with distilled water and anhydrous ethanol. After drying, you will obtain a polyvinyl alcohol hemostatic sponge for combat wound first aid. This hemostatic sponge can be compressed using specific equipment and then sterilized with ethylene oxide and sealed for storage.

[0081] Example 3

[0082] Operating steps:

[0083] Step 1: Cut the purchased medical-grade polyvinyl alcohol sponge into 1×1×8cm pieces. 3 The long strips were ultrasonically cleaned three times with anhydrous ethanol and then dried for later use.

[0084] Step 2: Weigh 1g of dopamine hydrochloride and dissolve it in 50ml of tris(hydroxymethyl)aminomethane buffer solution with a pH of 9.5, and sonicate until the solid is completely dissolved.

[0085] Step 3: Immerse the polyvinyl alcohol sponge treated in Step 1 completely in the hydrochloric acid dopamine solution prepared in Step 2, sonicate for 10-30 minutes, and stir at room temperature (25°C) for 24 hours.

[0086] Step 4: After the reaction is complete, remove the sponge and rinse it repeatedly with distilled water, then dry it for later use.

[0087] Step 5: Add carboxymethyl chitosan, gelatin and methacrylamide gelatin to distilled water and stir until completely dissolved, so that the mass concentrations of carboxymethyl chitosan, gelatin and methacrylamide gelatin are 3%, 3% and 3% respectively. Adjust the pH of the solution to 9.2 with tris(hydroxymethyl)aminomethane buffer, immerse the dopamine-modified polyvinyl alcohol sponge, and stir at room temperature (25°C) for 10 hours.

[0088] Step 6: Rinse the modified sponge repeatedly with distilled water, then immerse the sponge in 60 ml of 4% sodium methacrylamide aqueous solution, add 0.012 g of sodium persulfate / sodium thiosulfate (mass ratio 3:1) under a nitrogen atmosphere, and react at 35°C for 8 h.

[0089] Step 7: After the reaction is complete, remove the sponge and repeatedly soak and wash it with distilled water and anhydrous ethanol. After drying, you will obtain a polyvinyl alcohol hemostatic sponge for combat wound first aid. This hemostatic sponge can be compressed using specific equipment and then sterilized with ethylene oxide and sealed for storage.

[0090] Example 4:

[0091] Step 1: Cut the purchased medical-grade polyvinyl alcohol sponge into 1×1×8cm pieces. 3 The long strips were ultrasonically cleaned three times with anhydrous ethanol and then dried for later use.

[0092] Step 2: Weigh 0.5g of tannic acid and dissolve it in 60ml of tris(hydroxymethyl)aminomethane buffer solution with a pH of 9.2, and sonicate until the solid is completely dissolved;

[0093] Step 3: Immerse the polyvinyl alcohol sponge treated in Step 1 completely in the tannic acid solution prepared in Step 2, sonicate for 10-30 minutes, and stir at room temperature (25°C) for 30 hours.

[0094] Step 4: After the reaction is complete, remove the sponge and rinse it repeatedly with distilled water, then dry it for later use.

[0095] Step 5: Add alkylated chitosan to distilled water and stir until completely dissolved to a mass concentration of 5%. Adjust the pH of the solution to 8.8 with sodium hydroxide. Immerse the tannic acid-modified polyvinyl alcohol sponge in the solution and stir at room temperature (25°C) for 13 hours.

[0096] Step 6: Rinse the modified sponge repeatedly with distilled water, then immerse the sponge in 50 ml of 3% aqueous solution of methacrylamide gelatin. Under a nitrogen atmosphere, add 0.009 g of 2,2'-azo[2-(2-imidazolinyl)propane] dihydrochloride and react at 42 °C for 7 h.

[0097] Step 7: After the reaction is complete, remove the sponge and repeatedly soak and wash it with distilled water and anhydrous ethanol. After drying, you will obtain a polyvinyl alcohol hemostatic sponge for combat wound first aid. This hemostatic sponge can be compressed using specific equipment and then sterilized with ethylene oxide and sealed for storage.

[0098] Comparative Example 1

[0099] Operating steps:

[0100] Step 1: Cut the purchased medical-grade polyvinyl alcohol sponge into 1cm pieces. 3 The small cubes were ultrasonically cleaned three times with anhydrous ethanol and then dried for later use.

[0101] Step 2: Weigh 0.16g of dopamine hydrochloride and dissolve it in 30ml of tris(hydroxymethyl)aminomethane buffer solution with a pH of 8.5, and sonicate until the solid is completely dissolved;

[0102] Step 3: Immerse the polyvinyl alcohol sponge treated in Step 1 completely in the hydrochloric acid dopamine solution prepared in Step 2, sonicate for 10-30 minutes, and stir at room temperature (25°C) for 40 hours.

[0103] Step 4: After the reaction is complete, the sponge is removed and repeatedly rinsed with distilled water and dried to obtain dopamine-modified polyvinyl alcohol sponge.

[0104] Comparative Example 2

[0105] Operating steps:

[0106] Step 1: Cut the purchased medical-grade polyvinyl alcohol sponge into 1cm pieces. 3 The small cubes were ultrasonically cleaned three times with anhydrous ethanol and then dried for later use.

[0107] Step 2: Weigh 0.16g of dopamine hydrochloride and dissolve it in 30ml of tris(hydroxymethyl)aminomethane buffer solution with a pH of 8.5, and sonicate until the solid is completely dissolved;

[0108] Step 3: Immerse the polyvinyl alcohol sponge treated in Step 1 completely in the hydrochloric acid dopamine solution prepared in Step 2, sonicate for 10-30 minutes, and stir at room temperature (25°C) for 40 hours.

[0109] Step 4: After the reaction is complete, remove the sponge and rinse it repeatedly with distilled water, then dry it for later use.

[0110] Step 5: Add carboxymethyl chitosan and methacrylamide gelatin to distilled water and stir until completely dissolved, so that the mass concentrations of carboxymethyl chitosan and methacrylamide gelatin are 4% and 3% respectively. Adjust the pH of the solution to 8.5 with sodium hydroxide, immerse the dopamine-modified polyvinyl alcohol sponge, and stir at room temperature (25°C) for 16 hours.

[0111] Step 6: Soak and rinse the modified sponge repeatedly with distilled water, and dry it to obtain a single-layer modified polyvinyl alcohol hemostatic sponge.

[0112] Method for determining in vitro coagulation time of polyvinyl alcohol sponge:

[0113] Take 0.05g of each of Examples 1-3, Comparative Examples 1-2, and polyvinyl alcohol medical sponge, and 0.1mL of each of 0.01mol / L PBS solution (pH 7.4) to prepare suspensions of the above raw materials. Place each group of solutions in a glass test tube and incubate at 37℃ for 2 minutes. Add 1mL of fresh whole blood drawn from the marginal ear vein of a New Zealand rabbit to each of the above mixtures and record the time immediately. After mixing thoroughly, continue incubation at 37℃. Tilt the glass test tube 90° every 10 seconds to observe whether the blood coagulates until the blood completely loses its fluidity, and record the coagulation time. Repeat each sample 6 times.

[0114] The test results are shown in Table 1.

[0115] Table 1 shows the in vitro coagulation time test results of Examples 1-4, Comparative Examples 1-2, and polyvinyl alcohol medical sponge.

[0116]

Claims

1. A polyvinyl alcohol sponge, comprising a polyvinyl alcohol sponge matrix and a polyphenolic compound layer on its surface, wherein a polymer with coagulation function is grafted to the surface of the polyvinyl alcohol sponge matrix via the polyphenolic compound.

2. The polyvinyl alcohol sponge according to claim 1, characterized in that: The coagulation-functional polymers include natural polymers with amino groups and natural polymers with double bond functionalization. Wherein, the amino-containing natural polymer is selected from at least one of chitosan or its derivatives, and gelatin; the double-bond functionalized natural polymer is selected from at least one of the following double-bond functionalized natural polymers: chitosan or its derivatives, cellulose or its derivatives, gelatin, and alginate; and / or, Double bond functionalization to methacrylation; and / or, The polyphenolic compounds are selected from at least one of dopamine, tannic acid, or gallic acid.

3. The method for preparing polyvinyl alcohol sponge according to claim 1 or 2, comprising forming a polyphenolic compound layer on a polyvinyl alcohol sponge matrix, then loading polymer A through a Schiff base reaction, and finally adding double-bond functionalized polymer B for free radical polymerization.

4. The preparation method according to claim 3, characterized in that... Includes the following steps: (1) Polyphenolic compounds are used to modify the polyvinyl alcohol sponge matrix to form a polyphenolic compound layer on the surface of the polyvinyl alcohol sponge matrix; (2) Immerse the modified polyvinyl alcohol sponge in a solution of polymer A; (3) The polyvinyl alcohol sponge obtained in step (2) is then immersed in a solution of double bond functionalized polymer B, and a free radical initiator is added to carry out the reaction.

5. The preparation method according to claim 4, characterized in that... Step (1) includes: The polyvinyl alcohol sponge matrix is ​​immersed in a polyphenol compound solution, sonicated for 10–30 minutes, and then stirred at 10–30°C for 8–48 hours. Preferably, the mass concentration of the polyphenol compound solution is 0.2% to 5%, more preferably 0.5% to 3%; and / or, the pH of the polyphenol compound solution is 8 to 10.

6. The preparation method according to claim 4, characterized in that... In step (2): The polymer A is selected from at least one of chitosan or its derivatives, gelatin, double-bond functionalized chitosan or its derivatives, and double-bond functionalized gelatin; and / or, The pH of the solution of polymer A is 8–10; and / or, The mass concentration of the polymer A solution is 1% to 20%, preferably 4% to 10%.

7. The preparation method according to claim 4, characterized in that... In step (2): Soaking time is 10–16 hours; and / or, The soaking temperature is 10-30℃.

8. The preparation method according to claim 4, characterized in that... In step (3): The polymer B is selected from at least one of the following double-bond functionalized natural polymers: chitosan or its derivatives, cellulose or its derivatives, gelatin, alginate; and / or, The mass concentration of the solution of double-bond functionalized polymer B is 1%–20%, preferably 4%–10%; and / or, The free radical initiator is a water-soluble azo initiator and / or a redox initiator. Preferably, the azo initiator is selected from at least one of 2,2-azobisisobutyrate, 2,2'-azo[2-(2-imidazolinyl)propane]dihydrochloride, and azobisisobutyramidine hydrochloride. The redox initiator includes an oxidant and a reductant. The oxidant is selected from at least one of potassium persulfate, sodium persulfate, and hydrogen peroxide. The reductant is selected from at least one of sodium thiosulfate, ferrous chloride, and ascorbic acid. And / or, The amount of the free radical initiator is 0.2% to 1.5% of the total mass of the double-bond functionalized polymer B.

9. The preparation method according to claim 4, characterized in that... In step (3): The reaction time is 4–8 hours; and / or, The reaction temperature is 20–80℃.

10. The application of the polyvinyl alcohol sponge according to any one of claims 1 to 2 or the preparation method according to any one of claims 3 to 9 in hemostatic materials.

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