Silicon-containing polymer doped hemostatic sponge material and preparation method thereof

Abstract

The invention provides a silicon-containing polymer doped hemostatic sponge material and a preparation method thereof, and the preparation method mainly comprises the following steps: mixing chitosan, a cross-linking agent, polyvinyl alcohol and a silicon-containing polymer for reaction to obtain the silicon-containing polymer doped hemostatic sponge material. The hemostatic sponge material prepared by the preparation method disclosed by the invention has excellent water absorption, rebound resilience and biocompatibility.

Description

Technical Field

[0001] The present invention belongs to the technical field of biochemistry, and particularly relates to a hemostatic sponge material doped with a silicon-containing polymer and a preparation method thereof. Background Art

[0002] In the surgical operations and nursing during the clinical medical treatment of the injured patients, effective hemostasis of the wound surface can not only avoid shock caused by excessive blood loss, but also effectively reduce the risk of wound infection caused by bleeding. Traditional hemostatic materials mainly include cotton gauze and tourniquets. The advantages are low cost, but they are prone to adhesion between the gauze and the wound, and sometimes cause secondary cracking of the wound during dressing change. In the actual production and life scenarios, if encountering injuries with massive bleeding, cotton gauze hemostatic materials are difficult to meet the requirements. Therefore, the academic and industrial communities have been in search of hemostatic materials made of new materials.

[0003] Hydrogel materials and inorganic hemostatic powders used for hemostasis are important components of hemostatic materials. The former can effectively reduce the temperature of the affected area during application to relieve the pain of the injured by using its water component; the latter is applied to the wound through its inorganic component, and blocks blood vessels and plays a role in sterilization and anti-inflammatory by generating local high temperature. However, hydrogel materials are difficult to cope with massive wound bleeding, and inorganic hemostatic powders cannot provide comprehensive coverage and protection for the wound. Combining the clinical rescue requirements of convenient operation and easy storage, hemostatic sponge materials have gradually emerged in recent years. On the one hand, hemostatic sponge materials have the advantages of convenient processing and easy storage, and are suitable for large-scale industrial production; on the other hand, medical sponge materials not only have a wide range of sources but also excellent hemostatic performance, and can effectively block massive bleeding conditions in addition to daily care and treatment. Compared with artificially prepared polymer hemostatic sponge materials, natural polymer materials are increasingly used as raw materials for preparing hemostatic sponge materials because of their wide sources and good biocompatibility. Among many natural polymer materials, chitosan materials have become the first choice for clinical medical materials because of their wide sources and antibacterial properties. As early as 1934, the first chitosan-related patent was published in the United States. In 1941, artificial skin and surgical sutures made of chitosan materials were successfully developed. After the 1990s, the annual global output of chitosan reached tens of thousands of tons. Since chitosan has low solubility, chemical modification of chitosan materials can significantly improve their solubility, mainly including quaternary ammonium salt chitosan after N-alkylation, carboxymethyl chitosan after carboxymethylation, and cross-linked chitosan obtained by cross-linking reaction. Quaternary ammonium salt chitosan materials are mainly used for scar repair after various traumas, mainly in the forms of gels, capsules and liquids; carboxymethyl chitosan materials with increased water solubility due to the introduction of carboxymethyl groups are widely used in the field of medical beauty, especially as a moisturizing functional component in products such as facial masks, essences and moisturizers.

[0004] Although natural polymer hemostatic sponge materials, especially chitosan-modified sponge hemostatic materials, have received the attention of many scientific researchers and surgeons, in the process of medical rescue, more complex rescue scenarios need to be dealt with. It is required to have excellent blood absorption ability, outstanding mechanical strength, and still maintain its shape without deformation after absorbing blood during the application process, so as to perform complex operations such as hemostasis and pressing during surgical rescue operations. However, to improve the mechanical properties of traditional chitosan sponge hemostatic materials, it is often necessary to increase the amount of cross-linking agent added to the chitosan reaction solution. Although the mechanical properties of the chitosan material can be improved when it is prepared into a hemostatic sponge material, other properties of the material will be weakened. Therefore, it is of great significance to develop a solid filler to improve the mechanical strength of chitosan sponge hemostatic materials without affecting their hemostatic performance. Summary of the Invention

[0005] The purpose of the present invention is to provide a hemostatic sponge material doped with a silicon-containing polymer, which has excellent mechanical properties, water absorption properties and biocompatibility.

[0006] In the first aspect of the present invention, a preparation method of a hemostatic sponge material doped with a silicon-containing polymer is provided, which is characterized in that it mainly includes the following steps: mixing and reacting chitosan, a cross-linking agent, polyvinyl alcohol with the silicon-containing polymer to obtain a hemostatic sponge material doped with a silicon-containing polymer.

[0007] Further preferably, the silicon-containing polymer refers to a silicon-containing material modified by a silane coupling agent and coupled with a polymer.

[0008] Further preferably, the silicon-containing inorganic material is treated with a silane coupling agent and reacts with a monomer under the action of an initiator to obtain the silicon-containing polymer.

[0009] Further preferably, the silicon-containing inorganic material contains silicon dioxide.

[0010] Further preferably, the silicon-containing inorganic material is selected from silicon dioxide, zeolite, kaolin, diatomite, montmorillonite, quartz, ceramics or glass; more preferably silicon dioxide.

[0011] Further preferably, the morphology of the silicon-containing inorganic material is powder or microsphere.

[0012] Further preferably, the particle size of the powder or microspheres is selected from any one of the following particle size scales or the range between any two particle size scales: 0.1μm, 0.15μm, 0.2μm, 0.25μm, 0.3μm, 0.35μm, 0.4μm, 0.45μm, 0.5μm, 0.55μm, 0.6μm, 0.65μm, 0.7μm, 0.75μm, 0.8μm, 0.85μm, 0.9μm, 0.95μm, 1μm, 1.5μm, 2μm, 2.5μm, 3μm, 3.5μm, 4μm, 4.5μm, 5μm, 5.5μm, 6μm, 6.5μm, 7μm, 7.5μm, 8μm, 8.5μm, 9μm, 9.5μm, 10μm, 15μm, 20μm, 25μm, 30μm, 35μm, 40μm, 45μm, 50μm, 55μm, 60μm, 65μm, 70μm, 75μm, 80μm, 85μm, 90μm, 95μm, 100μm, 150μm, 200μm, 250μm, 300μm, 350μm, 400μm, 450μm, 500μm, 550μm, 600μm, 650μm, 700μm, 750μm, 800μm, 850μm, 900μm, 950μm, 1000μm; the particle size is the average value;

[0013] One of the preferred modes, the particle size is selected from 0.1 - 10μm;

[0014] One of the preferred modes, the particle size is selected from 0.2 - 6μm;

[0015] One of the preferred modes, the particle size is selected from 0.4 - 5μm;

[0016] One of the preferred modes, the particle size is selected from 0.5 - 3μm;

[0017] One of the preferred modes, the particle size is selected from 0.2 - 1μm;

[0018] One of the preferred modes, the particle size is selected from 0.5 - 1μm;

[0019] One of the preferred modes, the particle size is selected from 1μm - 100μm.

[0020] Further preferably, the structure of the silane coupling agent contains an unsaturated bond.

[0021] Further preferably, the silane coupling agent is selected from one or more of γ-methacryloxypropyltrimethoxysilane, vinyltriethoxysilane, vinyltrimethoxysilane, vinyltris(β-methoxyethoxy)silane, dimethylethenyethoxysilane, methylethenyldiethoxysilane or vinyltrimethoxysilane oligomer.

[0022] Further preferably, the initiator is selected from azo initiators, peroxide initiators or redox initiators.

[0023] Further preferably, the initiator is selected from one or more of 4,4'-azobis(4-cyanovaleric acid), azobisisobutyronitrile, azobisisoheptonitrile, dimethyl 2,2'-azobis(2-methylpropionate), 2,2'-azobis(2-methylpropionamidine) dihydrochloride, 2,2'-azobis(2-methyl-N-(2-hydroxyethyl)propionamide) dihydrochloride, and azoisobutyronitrile cyanamide.

[0024] Further preferably, the monomer is an acrylic monomer.

[0025] Further preferably, the monomer is selected from one or more of substituted or unsubstituted acrylic acid, acrylate, and acrylate ester.

[0026] Further preferably, the substituent is selected from alkyl, cycloalkyl, aryl, alkoxy, cycloalkoxy, aryloxy, etc.

[0027] Further preferably, the monomer is selected from one or more of alkyl acrylic acid, alkyl acrylate, or alkyl acrylate ester.

[0028] Further preferably, the acrylic monomer is selected from one or a combination of acrylic acid, methacrylic acid, methacrylate, methacrylate ester, methyl methacrylate, butyl acrylate, isooctyl acrylate.

[0029] Further preferably, the crosslinking agent is selected from glycidyl ether compounds.

[0030] Further preferably, the crosslinking agent is selected from one or more of n-butyl glycidyl ether, allyl glycidyl ether, 2-ethylhexyl glycidyl ether, phenyl glycidyl ether, cresyl glycidyl ether, glycidyl methacrylate, glycidyl tricarboxylate, diglycidyl ester, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, butanediol diglycidyl ether, trimethylolpropane triglycidyl ether, and glycerol triglycidyl ether; more preferably glycerol triglycidyl ether (GTE).

[0031] Further preferably, the feeding ratio (ml:ml) of the silicon-containing inorganic material to the silane coupling agent is (1-20):1, more preferably (5-10):1.

[0032] Further preferably, the feeding ratio (L:g) of the monomer to the initiator is (10-70):(10-50); more preferably 0.5-5:1; further preferably 0.5-2:1, and even more preferably any value or the interval range between any two values of 0.5:1, 0.6:1, 1:1, 1.5:1, or 2:1.

[0033] Further preferably, before the silicon-containing inorganic material is treated with a silane coupling agent, it further includes a pretreatment process, that is, before the silicon-containing inorganic material comes into contact with the silane coupling agent, the silicon-containing inorganic material is first ultrasonically washed, then reacted with an alkaline solution, and then washed again.

[0034] Further preferably, the alkaline solution is selected from one or more of hydroxide solutions, carbonate solutions, bicarbonate solutions, etc.

[0035] Further preferably, the pretreatment process further includes: (a) putting the silicon-containing inorganic material into deionized water and stirring for 10 - 60 minutes, and then ultrasonically cleaning for 10 - 60 minutes.

[0036] Further preferably, this step is repeated 2 - 3 times.

[0037] Further preferably, the pretreatment process further includes: (b) adding 5 - 50 g of sodium hydroxide to the system in batches, and stirring for 0.1 - 8 h under the condition that the reaction temperature is 15 - 80 °C.

[0038] Further preferably, the pretreatment process further includes: (c) washing the reacted microspheres with water or an alcohol solvent until the pH of the solution is 6 - 9.5.

[0039] Further preferably, the alcohol solvent is selected from ethanol.

[0040] Further preferably, the reaction temperature of the silicon-containing inorganic material and the silane coupling agent is 0 - 150 °C, more preferably 10 - 100 °C, and even more preferably 50 - 100 °C; the reaction time is 1 - 48 h, preferably 5 - 24 h.

[0041] Further preferably, after adding the monomer and the initiator and mixing them, the reaction system is sealed, bubbled, and then heated for reaction.

[0042] Further preferably, the bubbling time is 0.5 - 5 h, more preferably 1 - 2 h.

[0043] Further preferably, the heating temperature of this step is 50 - 150 °C, more preferably 60 - 100 °C.

[0044] Further preferably, the heating reaction time is 1 - 12 h, preferably 5 - 8 h.

[0045] Further preferably, the mixed reaction further includes: (d) dissolving chitosan in an acid solution and stirring for dissolution; (e) adding a crosslinking agent, polyvinyl alcohol, and a silicon-containing polymer to (d) and stirring for reaction; (f) introducing the reaction solution into a mold and freeze-drying to obtain a hemostatic sponge material doped with a silicon-containing polymer.

[0046] Further preferably, the acid solution is an acetic acid solution.

[0047] Further preferably, the feeding ratio (g: ml: g) of the chitosan, the crosslinking agent and the polyvinyl alcohol is (1 - 10): (0.1 - 1): (0.1 - 5); more preferably, the feeding ratio (g: ml: g) of the chitosan, the crosslinking agent and the polyvinyl alcohol is 1: (0.1 - 0.5): (0.5 - 5).

[0048] Further preferably, the reaction temperature in step (d) is 0 - 40°C, preferably at room temperature.

[0049] Further preferably, the reaction temperature in step (e) is 0 - 40°C, preferably at room temperature.

[0050] Further preferably, the reaction time in step (e) is 12 - 56 h, preferably 24 - 48 h.

[0051] Further preferably, in step (f), the freeze-drying time is 12 - 72 h, preferably 24 - 36 h.

[0052] The second aspect of the present invention provides a hemostatic sponge material containing a silicon polymer composite doping prepared by the method described in the first aspect of the present invention.

[0053] The third aspect of the present invention provides the use of a hemostatic sponge material containing a silicon polymer composite doping prepared by the method described in the first aspect of the present invention or the hemostatic sponge material containing a silicon polymer composite doping described in the second aspect of the present invention in the preparation of materials for hemostasis, wound healing or wound anti-inflammation. Description of the Drawings

[0054] Figure 1 It is the infrared spectrum of the chitosan hemostatic sponge material prepared in Example 1.

[0055] Figure 2 It is the infrared spectrum of the chitosan hemostatic sponge material prepared in Example 2.

[0056] Figure 3 It is the infrared spectrum of the chitosan hemostatic sponge material prepared in Example 3.

[0057] Figure 4 It is the infrared spectrum of the chitosan hemostatic sponge material prepared in Example 4.

[0058] Figures 5 to 7 They are respectively the resilience experiments of the chitosan hemostatic sponge materials prepared in Examples 2 - 4, where Figure 5 .1, 6.1, 7.1 all represent the initial state, Figure 5.2, 6.2, and 7.2 all represent the states when pressed by heavy objects. Figure 5 .3, 6.3, and 7.3 all represent the states after rebounding from the pressure.

[0059] Figure 8 It is the water absorption experiment of the chitosan hemostatic sponge materials prepared from Example 1 to Example 4. Detailed implementation manners

[0060] The following further elaborates the present invention in combination with the detailed implementation manners and examples. Please refer to the accompanying drawings together. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention. For the experimental methods without specific conditions in the following examples, first follow the conditions guided by the detailed implementation manners described above, and then follow the conventional conditions, such as those described in "Sambrook et al., Molecular Cloning: A Laboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989)", "Cell-Free Protein Synthesis Experimental Manual" "Edited by Alexander S. Spirin and James R. Swartz. Cell-free protein synthesis: methods and protocols [M]. 2008" and other documents, or the conditions recommended by the manufacturer.

[0061] Unless otherwise stated, the percentages and parts mentioned in the present invention are weight percentages and weight parts.

[0062] Unless otherwise specified, the materials and reagents used in the embodiments of the present invention are all commercially available products.

[0063] Unless otherwise specified, the temperature unit in this application is Celsius (°C).

[0064] Nouns and terms

[0065] The following are the explanations or descriptions of the meanings of some relevant "nouns" and "terms" adopted in the present invention, so as to better understand the present invention. The corresponding explanations or descriptions apply to the whole text of the present invention, both to the following text and to the above text. When the present invention involves citing documents, the definitions of relevant terms, nouns, and phrases in the cited documents are also cited. However, when there is a conflict with the definitions in the present invention, the definitions in the present invention shall prevail. When there is a conflict between the definitions in the cited documents and the definitions in the present invention, it does not affect the components, substances, compositions, materials, systems, formulations, types, methods, equipment, etc. determined in the cited documents to be used as they are.

[0066] The polymer, which broadly includes oligomers and polymers in the present invention, has at least three structural units or a molecular weight of at least 500 Da (the molecular weight can be characterized by suitable methods, such as number-average molecular weight, weight-average molecular weight, viscosity-average molecular weight, etc.).

[0067] Acrylic monomer molecules: Monomer molecules that can be used to synthesize acrylic polymers, having a basic structure of C(COO-)=C. For example, CH(COOH)=CH2, CH(COONa)=CH2, CH3C(COOH)=CH2, CH3C(COONa)=CH2, CH(COOCH3)=CH2, CH(COOCH2CH2OH)=CH2, CH3C(COOCH3)=CH2, CH3C(COOCH2CH2OH)=CH2, etc.

[0068] The "fixing" methods such as fixing, fixed to, fixed with, fixed on, etc. refer to covalent binding methods.

[0069] The "connecting" / "binding" methods such as carrying, connected with, connected to, connected at, binding, capturing, captured to, etc. are not particularly limited, including but not limited to covalent methods, non-covalent methods, etc.

[0070] The purified substrate, also called the target substance, is the substance to be separated from the mixed system. The purified substrate in the present invention is not particularly limited. For example, it is a protein substance (also called the target protein at this time).

[0071] The "modified" products include but are not limited to derivatives, modified products, genetically modified products, fusion products, etc. of the present invention, which can maintain the original functions or properties, or can optimize or change their functions or properties.

[0072] Binding force: The binding ability, such as the binding ability of a biomicrosphere to a certain protein.

[0073] Affinity force: The substrate concentration when the biomicrosphere binds only 50% of the substrate using substrate solutions with different concentration gradients.

[0074] "Optionally" means that it can be present or absent, and the selection criterion is to be able to implement the technical solution of the present invention.

[0075] In the present invention, the "optional method" means that as long as it is applicable to the technical solution of the present invention, it can be used to implement the present invention.

[0076] In the present invention, the preferred embodiments such as "preferred", "more preferred", "most preferred", etc. do not constitute any limitation on the scope of coverage and protection scope of the invention, and are not used to limit the scope and implementation manner of the present invention, but are only used to provide some embodiments as examples.

[0077] In the description of the present invention, for the preferred manners such as "one of the preferences", "one of the preferred manners", "one of the preferred embodiments", "one of the preferred examples", "preferred examples", "in a preferred embodiment", "in some preferred examples", "in some preferred manners", "preferably", "preferred", "preferably", "more preferably", "more preferably", "further preferably", "most preferably", etc., and the illustrative listing manners such as "one of the embodiments", "one of the manners", "examples", "specific examples", "for example", "as an example", "for example", "such as", "like", etc., they do not constitute any limitation on the scope of coverage and the scope of protection of the invention in any sense, and the specific features described by each manner are included in at least one specific embodiment of the present invention. In the present invention, each manner

[0078] The specific features described by each manner can be combined in a suitable manner in any one or more specific embodiments. In the present invention, the technical features or technical solutions corresponding to each preferred manner can also be combined by any suitable means.

[0079] In the present invention, "any combination thereof" means "greater than 1" in terms of quantity and means the group formed by the following situations: "optionally selecting any one, or the group formed by optionally selecting at least two of them".

[0080] In the present invention, the descriptions of "one or more", "one or more kinds", etc. with "one or more" have the same meaning as "at least one", "at least one kind", "its combination", "or its combination", "and its combination", "or any combination thereof", "and any combination thereof", etc., and can be used interchangeably, indicating that the quantity is equal to "1" or "greater than 1".

[0081] In the present invention, the use of "or / and", "and / or" means "optionally selecting one or optionally selecting its combination", and also means at least one.

[0082] The prior art means described in the present invention in manners such as "usually", "conventionally", "generally", "often", "tend to", etc. are also cited as references for the content of the present invention. Without special instructions, they can be regarded as one of the preferred manners of some technical features of the present invention, and it should be noted that they do not constitute any limitation on the scope of coverage and the scope of protection of the invention in any sense.

[0083] All the documents mentioned in the present invention and the documents directly or indirectly cited by these documents are cited as references in this application, just as if each document is cited separately as a reference.

[0084] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described hereinafter (including but not limited to the embodiments) can be combined with each other to form new or preferred technical solutions, as long as they can be used to implement the present invention. Due to space limitations, they will not be elaborated one by one. Specific Embodiment

[0086] Embodiment 1

[0087] (1) Add 5 g of chitosan solid to an acetic acid aqueous solution (1 mL of 99.8% acetic acid solution and 200 mL of distilled water solution), and mechanically stir at room temperature until the chitosan solid is completely dissolved and the solution has a certain viscosity;

[0088] (2) Add 1 mL of GTE as a crosslinking agent to the above reaction solution, and then continue mechanical stirring for 24 h;

[0089] (3) Pour the reaction solution into a mold and place it in a freeze dryer. After low-temperature freeze-drying for 24 h, a chitosan hemostatic sponge material is obtained (for the measured infrared spectrum data, see Figure 1 ).

[0090] Embodiment 2

[0091] (1) Add 5 g of chitosan solid to an acetic acid aqueous solution (1 mL of 99.8% acetic acid solution and 200 mL of distilled water solution), and mechanically stir at room temperature until the chitosan solid is completely dissolved and the solution has a certain viscosity;

[0092] (2) Add 0.5 mL of GTE to the above reaction solution, and then continue mechanical stirring for 24 h;

[0093] (3) Pour the reaction solution into a mold and place it in a freeze dryer. After low-temperature freeze-drying for 24 h, a chitosan hemostatic sponge material is obtained (for the measured infrared spectrum data, see Figure 2 ).

[0094] Embodiment 3

[0095] (1) Add 5 g of chitosan solid to an acetic acid aqueous solution (1 mL of 99.8% acetic acid solution and 200 mL of distilled water solution), and mechanically stir at room temperature until the chitosan solid is completely dissolved and the solution has a certain viscosity;

[0096] (2) Add 0.5 mL of GTE and 2.5 g of polyvinyl alcohol to the above reaction solution, and then continue mechanical stirring for 24 h;

[0097] (4) Pour the reaction solution into a mold and place it in a freeze dryer. After low-temperature freeze-drying for 50 h, a polyvinyl alcohol-doped chitosan hemostatic sponge material is obtained (for the measured infrared spectrum data, seeFigure 3 )。

[0098] Example 4:

[0099] 4.1 Pretreatment

[0100] Take 500 mL of silica microspheres (average particle size 100 μm), put them into a 10 L beaker, add deionized water and stir for 10 - 60 minutes, then ultrasonically clean for 10 - 60 minutes, repeat 3 times to obtain silica microspheres for standby;

[0101] Transfer the above silica microspheres to a reaction vessel, add 5 - 50 g of sodium hydroxide in batches, and stir for 0 - 8 h under the condition that the reaction temperature is 15 - 80 °C;

[0102] Use deionized water to repeatedly rinse the silica microspheres in (2) until the pH value of the cleaning solution is about 6 - 9.5.

[0103] 4.2 Preparation of silicon-containing polymer

[0104] (1) Take 50 mL of the silica microspheres treated in 4.1, wash them 2 times with absolute ethanol (100 mL in total), and then transfer them to a reaction vessel;

[0105] (2) Gradually add 100 mL of absolute ethanol under mechanical stirring conditions. While keeping the rotation speed not exceeding 240 revolutions per minute, add dropwise 10 mL of silane coupling agent γ-methacryloxypropyltrimethoxysilane, then raise the temperature to 50 °C and react for 24 hours, and then raise the temperature to 70 °C and continue to react for 2 hours;

[0106] (3) Wash with absolute ethanol three times, with a dosage of 100 mL each time; wash with deionized water 3 times, with a dosage of 200 mL each time;

[0107] (4) After washing, store the silica microspheres in deionized water, place them in a sealed container and store at 4 °C.

[0108] (5) Take 20 mL of the silica microspheres prepared in (4), add 80 mL of deionized water and then transfer them to a reaction vessel;

[0109] (6) Add acrylic acid monomer (15 mL) and initiator 4,4'-azobis(4-cyanovaleric acid) (30 mg) to the reaction system. After sealing the reaction system, keep stirring and pass nitrogen to bubble for 1 hour;

[0110] (7) Stir at 60 °C under heating conditions for 8 hours. After the reaction ends, open the sealed reaction system. After the reaction solution cools to room temperature, add 200 mL of sodium hydroxide solution (0.75 M) and stir for 3 hours;

[0111] (8) Transfer the reaction solution in (7) to 2 L of deionized water and let it stand for 24 hours. Then precipitate with sodium chloride, remove the supernatant, and wash with deionized water. Repeat this step three times, and store the silica microspheres in deionized water. Place them in a sealed container and store at 4 °C.

[0112] 4.3 Preparation of silica-polymer-doped chitosan hemostatic sponge material

[0113] (1) Add 5 g of chitosan solid to an acetic acid aqueous solution (1 mL of 99.8% acetic acid solution and 200 mL of distilled water solution), and mechanically stir at room temperature until the chitosan solid is completely dissolved and the solution has a certain viscosity.

[0114] (2) Add 0.5 mL of GTE, 2.5 g of polyvinyl alcohol, and 0.5 mL of silica microspheres to the above reaction solution, and then continue mechanical stirring for 24 h.

[0115] (4) Pour the reaction solution into a mold and place it in a freeze dryer. After low-temperature freeze drying for 50 h, obtain the silica-polymer-doped chitosan hemostatic sponge material (for the measured infrared spectrum data, see Figure 4 ).

[0116] Example Five Resilience Test

[0117] (1) Take out the freeze-fixed hemostatic sponge.

[0118] (2) First, measure and record the initial thickness.

[0119] (3) Add 300 mL of water to a 500 mL beaker.

[0120] (4) Place the beaker filled with water on top of the hemostatic sponge to apply pressure.

[0121] (5) Measure and record the thickness of the hemostatic sponge when pressure is applied.

[0122] (6) Remove the beaker applying pressure on the hemostatic sponge.

[0123] (7) Let the hemostatic sponge stand for 5 - 10 minutes.

[0124] (8) Record the thickness of the hemostatic sponge again to determine whether the hemostatic sponge has resilience (see Figures 5 - 7 ).

[0125] Since the material obtained in Example One has poor fluidity and cannot be poured out of the conical flask and cannot be freeze-dried, the resilience cannot be verified. Figure 5 In [reference], the initial thickness of the hemostatic sponge obtained in Example Two is 0.6 cm, the thickness when pressure is applied is 0.4 cm, and the thickness measured after removing the beaker and letting it stand for 5 - 10 minutes is 0.6 cm. Figure 6In Example 3, the initial thickness of the hemostatic sponge was 0.8 cm, the thickness under pressure was 0.6 cm, and the thickness measured after removing the beaker and allowing it to stand for 5 - 10 minutes was 0.8 cm. Figure 7 In Example 4, the initial thickness of the hemostatic sponge was 0.6 cm, the thickness under pressure was 0.5 cm, and the thickness measured after removing the beaker and allowing it to stand for 5 - 10 minutes was 0.6 cm.

[0126] It can be seen from this that the hemostatic sponge doped with a silicon polymer prepared by the method of the present invention can maintain excellent resilience; and compared with Example 2 and Example 3, the hemostatic sponge doped with a silicon polymer prepared by the method of the present invention has stronger mechanical strength.

[0127] Water absorption performance test of Example 6

[0128] Under normal temperature and pressure, take a small piece of the sponge to be tested. Four groups of the same weight are taken from the same sponge on average, and then they are respectively put into four centrifuge tubes, and an equal volume of distilled water is added and left for 24 hours. After 24 hours, pour out the excess water, then weigh the sponge, and finally calculate the data and take the average value (see Figure 8 ).

[0129] As Figure 8 can be seen, the hemostatic sponge material prepared by the method of the present invention has higher water absorption (the data of Example 1 is very unstable, and only one highest value is taken this time).

[0130] Biocompatibility test of Example 7

[0131] The biocompatibility of the chitosan hemostatic sponge material (prepared in Example 4) after adding silica - polymer was tested by the CCK - 8 method, and the results are shown in Table 1 below. This material has good biocompatibility.

[0132] Table 1

[0133]

[0134]

[0135] Note: The test item is: cytotoxicity experiment (CCK - 8 method)

[0136] Taking the above - mentioned ideal embodiment based on this application as an inspiration, through the above - mentioned description, relevant staff can completely make various changes and modifications without departing from the technical idea of this application. The technical scope of this application is not limited to the content in the specification, and its technical scope must be determined according to the scope of the claims.

Claims

1. A preparation method of a hemostatic sponge material doped with a silicon-containing polymer, characterized in that, It mainly includes: Mix chitosan, a crosslinking agent, polyvinyl alcohol with the silicon-containing polymer and react to obtain a hemostatic sponge material doped with the silicon-containing polymer, wherein the silicon-containing polymer refers to a silicon-containing material modified by a silane coupling agent and coupled with a polymer.

2. The preparation method according to claim 1, wherein Treat the silicon-containing inorganic material with a silane coupling agent and react with a monomer under the action of an initiator to obtain the silicon-containing polymer.

3. The preparation method of a hemostatic sponge material doped with a silicon-containing polymer according to claim 2, wherein, The silicon-containing inorganic material contains silicon dioxide.

4. The preparation method of a hemostatic sponge material doped with a silicon-containing polymer according to claim 2 or 3, characterized in that, The silicon-containing inorganic material is selected from silicon dioxide, zeolite, kaolin, diatomite, montmorillonite, quartz, ceramics or glass; more preferably silicon dioxide.

5. The preparation method of a hemostatic sponge material doped with a silicon-containing polymer according to any one of claims 2-4, characterized in that, The morphology of the silicon-containing inorganic material is powder or microspheres; preferably, the particle size of the powder or microspheres is selected from any one of the following particle size scales or the range between any two particle size scales: 0.1μm, 0.15μm, 0.2μm, 0.25μm, 0.3μm, 0.35μm, 0.4μm, 0.45μm, 0.5μm, 0.55μm, 0.6μm, 0.65μm, 0.7μm, 0.75μm, 0.8μm, 0.85μm, 0.9μm, 0.95μm, 1μm, 1.5μm, 2μm, 2.5μm, 3μm, 3.5μm, 4μm, 4.5μm, 5μm, 5.5μm, 6μm, 6.5μm, 7μm, 7.5μm, 8μm, 8.5μm, 9μm, 9.5μm, 10μm, 15μm, 20μm, 25μm, 30μm, 35μm, 40μm, 45μm, 50μm, 55μm, 60μm, 65μm, 70μm, 75μm, 80μm, 85μm, 90μm, 95μm, 100μm, 150μm, 200μm, 250μm, 300μm, 350μm, 400μm, 450μm, 500μm, 550μm, 600μm, 650μm, 700μm, 750μm, 800μm, 850μm, 900μm, 950μm, 1000μm; the particle size is the average value.

6. The preparation method of a hemostatic sponge material doped with a silicon-containing polymer according to any one of claims 1-5, characterized in that, The structure of the silane coupling agent contains an unsaturated bond; preferably, the silane coupling agent is selected from one or more of γ-methacryloxypropyltrimethoxysilane, vinyltriethoxysilane, vinyltrimethoxysilane, vinyltris(β-methoxyethoxy)silane, dimethylethenyethoxysilane, methylethenyldiethoxysilane or vinyltrimethoxysilane oligomer.

7. A method for preparing a hemostatic sponge material doped with a silicon-containing polymer according to any one of claims 1-6, characterized in that, The initiator is selected from azo initiators, peroxide initiators or redox initiators; preferably, the initiator is selected from one or more of 4,4'-azobis(4-cyanovaleric acid), azobisisobutyronitrile, azobisisoheptonitrile, dimethyl azobisisobutyrate, azobis(isobutyramidine)dihydrochloride, azobis(2-methylpropionamidine)dihydrochloride, azoisobutyronitrile carboxamide.

8. The preparation method of a hemostatic sponge material doped with a silicon-containing polymer according to any one of claims 1-7, characterized in that, The monomer is an acrylic monomer; preferably, the acrylic monomer is selected from one or more of substituted or unsubstituted acrylic acid, acrylate, and acrylate ester; further preferably, the monomer is selected from acrylic acid, sodium acrylate, methacrylic acid, methacrylate, methacrylate ester, methyl methacrylate, butyl acrylate, isooctyl acrylate, or a combination thereof.

9. The preparation method of a hemostatic sponge material doped with a silicon-containing polymer according to any one of claims 1-8, characterized in that, The crosslinking agent is selected from glycidyl ether compounds; preferably, the crosslinking agent is selected from one or more of n-butyl glycidyl ether, allyl glycidyl ether, 2-ethylhexyl glycidyl ether, phenyl glycidyl ether, cresyl glycidyl ether, glycidyl methacrylate, tertiary carboxylic acid glycidyl ester, diglycidyl ester, polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, butanediol diglycidyl ether, trimethylolpropane triglycidyl ether, and glycerol triglycidyl ether; more preferably glycerol triglycidyl ether (GTE).

10. The preparation method of a hemostatic sponge material doped with a silicon-containing polymer according to any one of claims 2-9, characterized in that, The feeding ratio (L:g) of the monomer to the initiator is (10-70):(10-50); preferably 0.5-5:1; more preferably 0.5-2:1, and further preferably any value or the interval range between any two values among 0.5:1, 0.6:1, 1:1, 1.5:1, or 2:

1.

11. A method for preparing a hemostatic sponge material doped with a silicon-containing polymer according to any one of claims 1-10, characterized in that, Before the silicon-containing inorganic material contacts the silane coupling agent, the silicon-containing inorganic material is first ultrasonically washed, then reacted with an alkaline solution, and then washed.

12. A method for preparing a hemostatic sponge material doped with a silicon-containing polymer according to any one of claims 1-11, characterized in that, The mixed reaction specifically includes: (d) dissolving chitosan in an acid solution and stirring to dissolve; (e) adding the crosslinking agent, polyvinyl alcohol, and the silicon-containing polymer to (d) and stirring to react; (f) introducing the reaction solution into a mold and freeze-drying to obtain the silicon-containing polymer-doped hemostatic sponge material.

13. According to the preparation method of a hemostatic sponge material doped with a silicon-containing polymer according to any one of claims 1-12, characterized in that, The feeding ratio (g:ml:g) of chitosan, the crosslinking agent, and polyvinyl alcohol is (1-10):(0.1-1):(0.1-5); a more preferred ratio is 1:(0.1-0.5):(0.5-5).

14. A silicon polymer-doped hemostatic sponge material prepared by the preparation method according to any one of claims 1-13.

15. Use of the silicon-containing polymer-doped hemostatic sponge material prepared by the preparation method according to any one of claims 1-14 or the silicon-containing polymer-doped hemostatic sponge material according to claim 13 in the preparation of a material for hemostasis, wound healing, or wound anti-inflammation.

Images