Polyvinyl alcohol sponge material and preparation method and application thereof

Abstract

This invention discloses a polyvinyl alcohol (PVA) sponge material, its preparation method, and its applications. The PVA sponge material is obtained from PVA through ice crystal pore formation and oxidative modification. The PVA sponge material obtained by this invention has a continuous porous structure, and the oxidatively modified PVA sponge possesses aldehyde and carboxyl groups, exhibiting active coagulation function and improving coagulation efficiency. Compared with traditional PVA sponge molding methods, this invention significantly reduces the amount of crosslinking agent aldehyde used, thereby reducing the risk of subsequent biotoxicity. It also avoids biotoxicity caused by incomplete surfactant rinsing and the large amount of wastewater generated during rinsing, which is beneficial for industrial applications.

Description

Technical Field

[0001] This invention relates to the field of polymer materials, and more specifically, to a polyvinyl alcohol sponge material, its preparation method, and its application. Background Technology

[0002] Polyvinyl alcohol (PVA) sponge is a three-dimensional porous material with high absorbency and elasticity. After absorbing liquid, it becomes soft, making patients feel comfortable and painless. It is easy to place and remove and can be cut to size as needed. It does not shed fibers and will not cause reinfection, so it is widely used in clinical surgery to replace absorbent cotton and gauze.

[0003] Currently, commercially available PVA sponges are produced by forming a three-dimensional network through an acetalization reaction, followed by foaming with surfactants to create porous PVA sponges with a through-pore structure. When used as a hemostatic material, PVA sponges primarily rely on their high water absorption to concentrate and aggregate platelets, thus achieving the hemostatic function.

[0004] Patent CN111116973A proposes a method for preparing a porous polyvinyl alcohol material with active hemostasis function. The method involves adding double bonds to the polyvinyl alcohol molecular chain and then copolymerizing it with a crosslinking agent, a photoinitiator, and a polymer with active hemostasis function under ultraviolet light irradiation to obtain a porous material. Although this method does not use a strong acid catalyst, it involves multiple reaction steps and uses organic solvents and foaming agents.

[0005] Patent CN201911334261.6 describes the preparation of hemostatic sponges by adding porous starch to cross-linked polyvinyl alcohol.

[0006] Patent CN201510122184.3 describes the preparation of a medical hemostatic sponge using sodium carboxymethyl cellulose, polyvinyl alcohol, and paloxam.

[0007] Patent CN202210945926.2 describes the preparation of a hemostatic sponge by blending chitosan, polyvinyl alcohol, sodium alginate, and quaternized gelatin, followed by crosslinking with genipin. All of these patents rely on the addition of natural polymers with hemostatic properties to achieve the active hemostatic function of PVA sponges, and most use surfactants for foaming, resulting in a very cumbersome post-washing process and the generation of large amounts of wastewater. Summary of the Invention

[0008] To address the problems existing in the prior art, this invention proposes a polyvinyl alcohol (PVA) sponge material, its preparation method, and its applications. This invention uses an ice crystal pore-forming method to prepare a porous PVA material, and then functionalizes the functional groups of the PVA through oxidative modification, thereby giving it active coagulation function and improving coagulation efficiency.

[0009] One objective of this invention is to provide a polyvinyl alcohol sponge material, which is obtained by polyvinyl alcohol through ice crystal pore formation and oxidative modification.

[0010] The polyvinyl alcohol sponge material of the present invention has a through-hole structure.

[0011] The polyvinyl alcohol sponge material described in this invention is a semi-crosslinked polyvinyl alcohol porous material with ice crystal pores, and the material has multiple functional groups such as hydroxyl, aldehyde and carboxyl groups.

[0012] The shape of the polyvinyl alcohol sponge material described in this invention varies depending on the application scenario, including but not limited to sheet-like, cylindrical, cubic, and other suitable shapes of different sizes.

[0013] The second objective of this invention is to provide a method for preparing the polyvinyl alcohol sponge material described in the first objective of this invention, comprising the steps of ice crystal formation and oxidative modification of polyvinyl alcohol.

[0014] Specifically, the preparation method includes the following steps:

[0015] (1) Add crystallization regulator, catalyst and crosslinking agent to polyvinyl alcohol solution to obtain a mixed system, pour it into mold and carry out freezing reaction;

[0016] (2) The mold was freeze-dried to remove moisture, and polyvinyl alcohol porous material was obtained;

[0017] (3) Immerse the polyvinyl alcohol porous material in an oxidation modification solution for oxidation modification.

[0018] In step (1),

[0019] The degree of polymerization of the polyvinyl alcohol is preferably 1500 to 2600. Specifically, the polyvinyl alcohol type may include, but is not limited to, 1788, 1792, 1799, 2488, 2492, and 2499.

[0020] The concentration of the polyvinyl alcohol solution is 1-20 wt%, preferably 2-5 wt%, for example, it can be 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 8 wt%, 10 wt%, 12 wt%, 15 wt%, 18 wt%, 20 wt%, etc.;

[0021] The crystallization regulator is a water-soluble inorganic salt, preferably at least one of sodium chloride, potassium chloride, calcium chloride, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium sulfate, potassium sulfate, and sodium phosphate.

[0022] The concentration of the crystallization regulator in the mixed system is 0.1-20 wt%, preferably 0.5-5 wt%, for example, it can be 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 8 wt%, 10 wt%, 12 wt%, 15 wt%, 18 wt%, 20 wt%, etc.;

[0023] The catalyst is a strong acid aqueous solution, which, upon addition, makes the pH of the mixed system 2-5; or the catalyst is a strong alkali aqueous solution, which, upon addition, makes the pH of the mixed system 8-11.

[0024] Strong acids can be sulfuric acid, hydrochloric acid, nitric acid, etc.; strong bases can be sodium hydroxide, potassium hydroxide, Tris buffer, etc.

[0025] The crosslinking agent is at least one of aldehyde crosslinking agents and epoxy crosslinking agents.

[0026] Aldehyde crosslinking agents are preferably selected from at least one of formaldehyde, glutaraldehyde, glyoxal, citral, and cinnamaldehyde; epoxy crosslinking agents are preferably selected from at least one of epichlorohydrin, butanediol diglycidyl ether, ethylene glycol diglycidyl ether, and polyethylene glycol diglycidyl ether.

[0027] The concentration of the crosslinking agent in the mixture is 0.001 to 10 wt%, preferably 0.01 to 1 wt%, for example, it can be 0.001 wt%, 0.005 wt%, 0.01 wt%, 0.05 wt%, 0.1 wt%, 0.5 wt%, 0.8 wt%, 1 wt%, 3 wt%, 5 wt%, 8 wt%, 10 wt%, etc.

[0028] The freezing reaction time is 24–72 h, preferably 30–70 h.

[0029] In step (2), the freeze-drying step to remove moisture can be performed using methods commonly found in the prior art, or can be appropriately adjusted according to the requirements of the actual situation.

[0030] In step (3),

[0031] The oxidizing agent is an aqueous solution of an oxidizing agent. Preferably, the oxidizing agent is selected from at least one of potassium permanganate, hydrogen peroxide, potassium dichromate, sodium periodate, Tempo reagent, and Jones reagent.

[0032] The concentration of the oxidative modification solution is 0.1-50 wt%, preferably 1-20 wt%, for example, it can be 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 8 wt%, 10 wt%, 12 wt%, 15 wt%, 18 wt%, 20 wt%, 30 wt%, 40 wt%, 50 wt%, etc.;

[0033] The oxidation modification time is 1 to 72 hours, preferably 4 to 24 hours.

[0034] A third objective of this invention is to provide the application of the polyvinyl alcohol sponge material or the preparation method thereof in hemostatic materials.

[0035] The beneficial effects of this invention are:

[0036] (1) Using ice crystals instead of surfactants as pore-forming agents for polyvinyl alcohol sponges can be removed by freeze drying, avoiding the biotoxicity caused by incomplete surfactant cleaning and the large amount of wastewater generated during cleaning, which is beneficial for industrial application.

[0037] (2) The use of cryogenic preparation of sponge can utilize the entanglement between molecular chains and hydrogen bonding of polyvinyl alcohol at low temperature to form a relatively stable physical crosslink. Compared with the traditional polyvinyl alcohol sponge molding method, the amount of crosslinking agent aldehyde used is greatly reduced. On the one hand, it can reduce the risk of subsequent biological toxicity, and on the other hand, it retains a large number of hydroxyl groups to facilitate subsequent functionalization modification.

[0038] (3) The oxidized polyvinyl alcohol sponge has aldehyde and carboxyl groups. The aldehyde group can chemically bond with amino groups in human tissues, and strongly adheres to the wound surface during hemostasis; the carboxyl group bonds with heme and Fe in hemoglobin. 2+ They combine to form a brown, sticky gel. Its own network structure can expand and compress the wound, thereby sealing capillaries to achieve hemostasis. In addition, the brown, sticky gel also has an adhesion and aggregation effect on platelets, which can accelerate blood clotting.

[0039] (4) Polyethylene glycol sponge has a perforated porous structure, which can quickly absorb liquid and expand. Combined with its active coagulation function, it can achieve rapid hemostasis of wounds. Furthermore, the sponge's flexible nature allows it to be made into different shapes to meet the needs of different application scenarios. Attached Figure Description

[0040] Figure 1 This is the SEM image of Example 1.

[0041] Figure 2 This is the SEM image of Comparative Example 1.

[0042] from Figure 1 and 2 It can be seen that the PVA sponge prepared by the ice crystal pore-forming method has a through-pore structure. The oxidation reaction does not destroy the structure of the sponge. The oxidized PVA sponge still maintains a porous structure, and the pores are interconnected. Detailed Implementation

[0043] The present invention will now be described in detail with reference to the accompanying drawings and 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.

[0044] 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.

[0045] 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.

[0046] According to a preferred embodiment of the present invention, the method for preparing polyvinyl alcohol sponge material may include the following steps:

[0047] Step 1: Take a certain amount of polyvinyl alcohol and add it to water, then heat and stir until completely dissolved;

[0048] Step 2: After cooling to room temperature, add crystallization regulator, catalyst and crosslinking agent, mix well and pour into mold, then place in refrigerator for freezing reaction;

[0049] Step 3: After reacting for a period of time, the mold is directly placed into a freeze dryer to remove moisture and obtain PVA porous material;

[0050] Step 4: After washing the porous material with distilled water, immerse it in the oxidation modification solution for reaction;

[0051] Step 5: After reacting for a period of time, remove the sponge and wash it repeatedly with distilled water and anhydrous ethanol. Dry it in an oven at 40°C to obtain a PVA hemostatic sponge with active coagulation function.

[0052] Step 6: The hemostatic sponge can be compressed using specific equipment and then sterilized with ethylene oxide and sealed for storage.

[0053] Based on the above technical solution, the polyvinyl alcohol model mentioned in step 1 includes, but is not limited to, 1788, 1792, 1799, 2488, 2492, 2499, etc.

[0054] Based on the above technical solution, the concentration of the polyvinyl alcohol aqueous solution in step 1 is 1-20 wt%, preferably 2-5 wt%.

[0055] Based on the above technical solution, the heating temperature in step 1 is 80-100℃.

[0056] Based on the above technical solution, the crystallization regulator in step 2 includes, but is not limited to, one or more of water-soluble inorganic salts such as sodium chloride, potassium chloride, calcium chloride, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium sulfate, potassium sulfate, and sodium phosphate. The concentration of the crystallization regulator is 0.1 to 20 wt%, preferably 0.5 to 5 wt%, when added to the polyvinyl alcohol solution.

[0057] Based on the above technical solution, the catalyst in step 2 is a strong acid aqueous solution such as sulfuric acid, hydrochloric acid, or nitric acid, added to make the pH value of the mixed system 2-5; or a strong alkaline aqueous solution such as sodium hydroxide, potassium hydroxide, or Tris buffer solution, added to make the pH value of the mixed system 8-11.

[0058] Based on the above technical solution, the crosslinking agent in step 2 includes, but is not limited to, aldehyde crosslinking agents such as formaldehyde, glutaraldehyde, glyoxal, citral, and cinnamaldehyde; or epoxy crosslinking agents such as epichlorohydrin, butanediol diglycidyl ether, ethylene glycol diglycidyl ether, and polyethylene glycol diglycidyl ether. The concentration of the crosslinking agent is 0.001–10 wt%, preferably 0.01–1 wt%.

[0059] Based on the above technical solution, the reaction time in step 3 is 24 to 72 hours.

[0060] Based on the above technical solution, the oxidative modification solution in step 4 includes, but is not limited to, aqueous solutions of oxidizing agents such as potassium permanganate, hydrogen peroxide, potassium dichromate, sodium periodate, Tempo reagent, and Jones reagent. The concentration of the oxidative modification solution is 0.1 to 50 wt%, preferably 1 to 20 wt%.

[0061] Based on the above technical solution, the oxidation reaction time in step 5 is 1 to 72 hours, preferably 4 to 24 hours.

[0062] Example 1

[0063] Operating steps:

[0064] Step 1: Add 1g of polyvinyl alcohol (1788) to 50g of water, heat to 95℃ and stir until completely dissolved;

[0065] Step 2: After cooling to room temperature, add 0.5g sodium chloride and 0.1g formaldehyde, adjust the pH of the solution to about 3 with concentrated sulfuric acid, stir and mix well, pour into a mold, and freeze in a refrigerator for reaction.

[0066] Step 3: After reacting for 30 hours, the mold is directly placed into a freeze dryer to remove moisture, thus obtaining PVA porous material;

[0067] Step 4: After washing the porous material with distilled water, immerse it in a 5% potassium permanganate aqueous solution for reaction.

[0068] Step 5: After reacting for 6 hours, remove the sponge and wash it repeatedly with distilled water and anhydrous ethanol. Dry it in an oven at 40°C to obtain a PVA hemostatic sponge with active coagulation function.

[0069] Step 6: The hemostatic sponge can be compressed using specific equipment and then sterilized with ethylene oxide and sealed for storage.

[0070] Example 2

[0071] Operating steps:

[0072] Step 1: Add 2g of polyvinyl alcohol (1799) to 70g of water, heat to 100℃ and stir until completely dissolved;

[0073] Step 2: After cooling to room temperature, add 1.4g potassium chloride and 0.03g glutaraldehyde, adjust the pH of the solution to about 2 with hydrochloric acid, stir and mix well, pour into a mold, and freeze in a refrigerator for reaction.

[0074] Step 3: After reacting for 48 hours, the mold is directly placed into a freeze dryer to remove moisture, thus obtaining PVA porous material;

[0075] Step 4: After washing the porous material with distilled water, immerse it in a 10% sodium periodate aqueous solution for reaction.

[0076] Step 5: After reacting for 16 hours, the sponge is removed and repeatedly washed with distilled water and anhydrous ethanol, and then dried in an oven at 40°C to obtain a PVA hemostatic sponge with active coagulation function.

[0077] Step 6: The hemostatic sponge can be compressed using specific equipment and then sterilized with ethylene oxide and sealed for storage.

[0078] Example 3

[0079] Operating steps:

[0080] Step 1: Add 3.2g of polyvinyl alcohol (2488) to 100g of water, heat to 85℃ and stir until completely dissolved;

[0081] Step 2: After cooling to room temperature, add 3.5g sodium sulfate and 0.5g butanediol diglycidyl ether. Adjust the pH of the solution to about 10 with sodium hydroxide solution. Stir and mix well, then pour into a mold and freeze in a refrigerator for reaction.

[0082] Step 3: After reacting for 48 hours, the mold is directly placed into a freeze dryer to remove moisture, thus obtaining PVA porous material;

[0083] Step 4: After washing the porous material with distilled water, immerse it in a 20% hydrogen peroxide solution for reaction.

[0084] Step 5: After reacting for 12 hours, the sponge is removed and repeatedly washed with distilled water and anhydrous ethanol, and then dried in an oven at 40°C to obtain a PVA hemostatic sponge with active coagulation function.

[0085] Step 6: The hemostatic sponge can be compressed using specific equipment and then sterilized with ethylene oxide and sealed for storage.

[0086] Example 4

[0087] Operating steps:

[0088] Step 1: Add 6.15g of polyvinyl alcohol (1792) to 150g of water, heat to 90℃ and stir until completely dissolved;

[0089] Step 2: After cooling to room temperature, add 7g of potassium carbonate and 0.12g of ethylene glycol diglycidyl ether. Adjust the pH of the solution to about 11 with Tris buffer solution. Stir and mix well, pour into a mold, and freeze in a refrigerator for reaction.

[0090] Step 3: After reacting for 70 hours, the mold is directly placed into a freeze dryer to remove moisture, thus obtaining PVA porous material;

[0091] Step 4: After washing the porous material with distilled water, immerse it in an 8% Tempo reagent aqueous solution for reaction;

[0092] Step 5: After reacting for 12 hours, the sponge is removed and repeatedly washed with distilled water and anhydrous ethanol, and then dried in an oven at 40°C to obtain a PVA hemostatic sponge with active coagulation function.

[0093] Step 6: The hemostatic sponge can be compressed using specific equipment and then sterilized with ethylene oxide and sealed for storage.

[0094] Comparative Example 1

[0095] Operating steps:

[0096] Step 1: Add 1g of polyvinyl alcohol (1788) to 50g of water, heat to 95℃ and stir until completely dissolved;

[0097] Step 2: After cooling to room temperature, add 0.5g sodium chloride and 0.1g formaldehyde, adjust the pH of the solution to about 3 with concentrated sulfuric acid, stir and mix well, pour into a mold, and freeze in a refrigerator for reaction.

[0098] Step 3: After reacting for 30 hours, the mold is directly placed into a freeze dryer to remove moisture, thus obtaining PVA porous material;

[0099] Step 4: Wash the porous material with distilled water and dry it in an oven at 40°C to obtain ice crystal porous PVA sponge.

[0100] Comparative Example 2

[0101] Medical PVA hemostatic sponge product.

[0102] Comparative Example 3

[0103] The medical PVA hemostatic sponge product is oxidized according to steps 4-6 of Example 1.

[0104] Methods for measuring in vitro coagulation time (APTT and PT) of polyvinyl alcohol sponge:

[0105] Activated partial thrombopslastin time (APTT) and prothrombin time (PT) are two important clinical indicators used to assess coagulation function. APTT is used to test intrinsic coagulation function, while PT is used to test the function of the extrinsic coagulation pathway.

[0106] Specific experimental methods: Fresh rabbit blood was obtained and centrifuged at 2500 rpm for 10 min, and the plasma was collected for later use. 0.05 g of Examples 1-4 and Comparative Examples 1-3 were thoroughly contacted with 50 μL of plasma and incubated at 37°C for 30 min. Three replicates were prepared for each sample. The incubated samples were transferred to cuvettes, and the corresponding APPT and PT detection reagents were added to the designated positions on the coagulation analyzer. The cuvettes were then placed sequentially in the detection row for measurement.

[0107] The test results are shown in Table 1.

[0108] Table 1 shows the results of in vitro coagulation time (APTT and PT) tests in Examples 1-4 and Comparative Examples 1-3.

[0109]

[0110] As shown in Table 1, the PVA sponge prepared using ice crystal pore formation has performance comparable to commercially available PVA hemostatic sponges, exhibiting a certain hemostatic function. However, after oxidation treatment, the in vitro clotting time is significantly shortened, with both APTT and PT less than 3 seconds, indicating that oxidation modification significantly improves the hemostatic performance of PVA.

[0111] Commercial PVA hemostatic sponges have improved hemostatic performance after oxidation treatment, but due to the limited number of reactive sites, their hemostatic performance is far lower than that of the embodiments of the present invention.

[0112] The present invention has been described in detail above with reference to specific embodiments and exemplary examples; however, these descriptions should not be construed as limiting the present invention. Those skilled in the art will understand that various equivalent substitutions, modifications, or improvements can be made to the technical solutions and embodiments of the present invention without departing from the spirit and scope of the invention, and all such modifications and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the appended claims.

[0113] All publications, patent applications, patents, and other references mentioned in this specification are incorporated herein by reference. Unless otherwise defined, all technical and scientific terms used in this specification have the meanings commonly understood by those skilled in the art. In case of conflict, the definitions in this specification shall prevail.

[0114] When this specification uses the prefixes “known to those skilled in the art,” “prior art,” or similar terms to derive materials, substances, methods, steps, apparatus, or components, the objects derived from such prefixes cover those commonly used in the art at the time of this application, but also include those that are not currently commonly used but will become generally recognized in the art as suitable for similar purposes.

[0115] In the context of this specification, except where expressly stated otherwise, any matters or issues not mentioned shall apply directly to those known in the art without any modification.

Claims

1. A polyvinyl alcohol sponge material, obtained by polyvinyl alcohol through ice crystal pore formation and oxidative modification.

2. A method for preparing a polyvinyl alcohol (PVA) sponge material, preferably used for preparing the PVA sponge material of claim 1, comprising the following steps: (1) Add crystallization regulator, catalyst and crosslinking agent to polyvinyl alcohol solution to obtain a mixed system, pour it into mold and carry out freezing reaction; (2) The mold was freeze-dried to remove moisture, and polyvinyl alcohol porous material was obtained; (3) Immerse the polyvinyl alcohol porous material in an oxidation modification solution for oxidation modification.

3. The method of claim 2, wherein In step (1): The degree of polymerization of the polyvinyl alcohol is 1500–2600; and / or, The concentration of the polyvinyl alcohol solution is 1–20 wt%, preferably 2–5 wt%.

4. The method of claim 2, wherein In step (1): The crystallization regulator is a water-soluble inorganic salt, preferably at least one selected from sodium chloride, potassium chloride, calcium chloride, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium sulfate, potassium sulfate, and sodium phosphate; and / or, The concentration of the crystallization regulator in the mixture is 0.1–20 wt%, preferably 0.5–5 wt%.

5. The method of claim 2, wherein In step (1): The catalyst is a strong acid aqueous solution, which, upon addition, adjusts the pH of the mixed system to 2–5; or the catalyst is a strong alkali aqueous solution, which, upon addition, adjusts the pH of the mixed system to 8–11.

6. The method of claim 2, wherein In step (1): The crosslinking agent is at least one of aldehyde crosslinking agents and epoxy crosslinking agents, preferably. The aldehyde crosslinking agent is selected from at least one of formaldehyde, glutaraldehyde, glyoxal, citral, and cinnamaldehyde; and / or, the epoxy crosslinking agent is selected from at least one of epichlorohydrin, butanediol diglycidyl ether, ethylene glycol diglycidyl ether, and polyethylene glycol diglycidyl ether; and / or, The concentration of the crosslinking agent in the mixture is 0.001–10 wt%, preferably 0.01–1 wt%.

7. The method of claim 2, wherein In step (1): The freezing reaction time is 24–72 hours.

8. The method of claim 2, wherein In step (3): The oxidizing agent is an aqueous solution of an oxidizing agent; preferably, the oxidizing agent is selected from at least one of potassium permanganate, hydrogen peroxide, potassium dichromate, sodium periodate, Tempo reagent, and Jones reagent.

9. The method of claim 2, wherein In step (3): The concentration of the oxidative modification solution is 0.1–50 wt%, preferably 1–20 wt%; and / or, The oxidation modification time is 1 to 72 hours, preferably 4 to 24 hours.

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

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