Hydrogel with hemostasis and oxidation resistance and preparation method thereof

Abstract

The invention relates to the field of medical cosmetology, in particular to hydrogel with hemostasis and oxidation resistance and a preparation method of the hydrogel. The hydrogel is prepared from an oyster shell and radix angelicae polysaccharide compound, a first network body and a second network body; the first network body and the second network body form a composite dual-network body; the oyster shell and radix angelicae polysaccharide compound is dispersed in the composite dual-network body; the first network body comprises agarose; the second colloid comprises a bisacrylamide copolymer; wherein the oyster shell and radix angelicae polysaccharide compound comprises a precipitate obtained by reacting an oyster shell substance with urea; and angelica dahurica polysaccharide; the surface of the precipitate is coated with the radix angelicae polysaccharide. The oyster shell and radix angelicae polysaccharide compound can be embedded into the composite dual-network body to regulate and control the pore diameter of the composite hydrogel, so that the pore diameter of the hydrogel is smaller, and the porosity is higher; hemostasis is facilitated; due to the composite double-network body structure, the toughness of the hydrogel is better, so that the application range of the hydrogel can be greatly expanded.

Description

Technical Field

[0001] The present application relates to the field of medical cosmetology, and in particular, to a hydrogel having hemostatic and antioxidant properties and a preparation method thereof. Background Art

[0002] Hemostatic gel has the function of coagulating wounds. The viscous colloid has a certain sealing effect on bleeding wounds and is more effective than ordinary bandages.

[0003] However, current hemostatic gels have limited application range. Summary of the invention

[0004] The purpose of the embodiments of the present application is to provide a hydrogel with hemostatic and antioxidant properties and a preparation method thereof.

[0005] In a first aspect, the present application provides a hydrogel having hemostatic and antioxidant properties, the hydrogel comprising:

[0006] Oyster shell angelica polysaccharide complex, a first network body, a second network body; the first network body and the second network body form a composite double network body structure; the oyster shell angelica polysaccharide complex is dispersed in the composite double network body structure; the first network body includes: agarose; the second network body includes: bisacrylamide copolymer;

[0007] The oyster shell and angelica polysaccharide complex comprises: a precipitate formed by the reaction of oyster shell substances and urea; and angelica polysaccharide; and the angelica polysaccharide is coated on the surface of the precipitate.

[0008] In the above technical scheme, the hydrogel includes an oyster shell angelica polysaccharide complex, a first network body, and a second network body; the first network body and the second network body form a composite double network body structure; the oyster shell angelica polysaccharide complex is dispersed in the composite double network body; the oyster shell angelica polysaccharide complex can be embedded in the composite double network body to regulate the pore size of the composite hydrogel, so that the pore size of the hydrogel is smaller and the porosity is higher; it is more conducive to hemostasis; further, the first network body includes: agarose; the second network body includes: bisacrylamide copolymer; the first network body and the second network body form a composite double network body; the first network body and the second network body form a composite double network body structure; the mechanical properties of the hydrogel are greatly improved compared with a single network, especially the hydrogel has better toughness, which is more conducive to its composite with the oyster shell angelica polysaccharide complex; the hydrogel has better toughness, thereby greatly expanding the application range of the hydrogel; it can be suitable for various parts (such as hemostasis in non-flat areas such as joints); and because this composite hydrogel has a more excellent pore structure; it can stop bleeding faster (especially suitable for scenes with large bleeding).

[0009] Further studies have found that some wound damage is usually accompanied by wound inflammation; currently there is no medical cosmetic material that can achieve hemostasis and anti-inflammation at the same time; further, in the above technical scheme, the oyster shell angelica polysaccharide complex contains a large amount of active calcium and antioxidant active ingredients, which is beneficial to hemostasis while scavenging free radicals, improving antioxidant efficacy, and is beneficial to wound recovery; the oyster shell angelica polysaccharide complex is combined with the aforementioned composite double network structure, which can greatly improve the hemostatic effect of the hydrogel while making the hydrogel have antioxidant properties, thereby improving the hemostatic effect while expanding the application field; for example, it can be expanded from the medical field to the beauty and skin care field.

[0010] In other embodiments of the present application, the loading amount of the above-mentioned Angelica dahurica polysaccharide on the surface of the precipitate is 5% to 20%.

[0011] In other embodiments of the present application, the second network body includes: a copolymer of lysine acrylamide, methacryloylethyl sulfobetaine, and methylene bisacrylamide.

[0012] In other embodiments of the present application, in the hydrogel, the percentage of the oyster shell angelica polysaccharide complex relative to the total mass of agarose, lysine acrylamide and methacryloylethyl sulfobetaine is 1% to 10%.

[0013] In a second aspect, the present application provides a method for preparing a hydrogel having hemostatic and antioxidant properties, comprising:

[0014] The oyster shell angelica polysaccharide complex is dispersed in the composite double network;

[0015] Wherein, the composite dual network body is formed by the first network body and the second network body;

[0016] The first network body includes: agarose; the second network body includes: bisacrylamide copolymer;

[0017] The preparation of the oyster shell and angelica polysaccharide complex comprises: reacting oyster shell materials with urea to obtain a precipitate; and coating the angelica polysaccharide on the surface of the precipitate.

[0018] In other embodiments of the present application, oyster shell material is reacted with urea to obtain a precipitate, comprising:

[0019] The oyster shell material is mixed with citrate and urea to undergo a hydration reaction to obtain a precipitate.

[0020] In other embodiments of the present application, preparing oyster shell material includes:

[0021] The oyster shells are calcined to obtain a sintered product.

[0022] In other embodiments of the present application, the oyster shell angelica polysaccharide complex is dispersed in a composite double network, including:

[0023] The agarose solution is mixed with the oyster shell angelica polysaccharide complex to obtain a mixture; then lysine acrylamide, methacryloylethyl sulfobetaine, methylenebisacrylamide and ammonium persulfate are added to the mixture for reaction.

[0024] In other embodiments of the present application, a second colloid mixture is prepared by mixing 5% to 15% agarose relative to the total mass percentage of lysine acrylamide, methacryloylethyl sulfobetaine and oyster shell angelica polysaccharide complex; 1% to 10% oyster shell angelica polysaccharide complex relative to the total mass percentage of agarose, lysine acrylamide and methacryloylethyl sulfobetaine; and 10% to 50% methacryloylethyl sulfobetaine relative to the total mass percentage of lysine acrylamide and methacryloylethyl sulfobetaine. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present application and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without paying creative work.

[0026] Figure 1 The pore structure diagram of the hydrogel prepared in each embodiment and comparative example is detected by scanning electron microscopy. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be clearly and completely described below. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments.

[0028] Therefore, the following detailed description of the embodiments of the present application is not intended to limit the scope of the present application for protection, but merely represents selected embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present application.

[0029] The present application provides a hydrogel having hemostatic and antioxidant properties, the hydrogel comprising:

[0030] Oyster shell angelica polysaccharide microspheres, a first network body, a second network body; the first network body and the second network body form a composite double network body; the oyster shell angelica polysaccharide microspheres are dispersed in the composite double network body; the first network body includes: agarose; the second network body includes: bisacrylamide copolymer;

[0031] The oyster shell and angelica polysaccharide complex comprises: a precipitate formed by the reaction of oyster shell substances and urea; and angelica polysaccharide; and the angelica polysaccharide is coated on the surface of the precipitate.

[0032] In the above technical scheme, the hydrogel includes an oyster shell angelica polysaccharide complex, a first network body, and a second network body; the first network body and the second network body form a composite double network body; the oyster shell angelica polysaccharide complex is dispersed in the composite double network body; the oyster shell angelica polysaccharide complex can be embedded in the composite double network body to regulate the pore size of the composite hydrogel, so that the pore size of the hydrogel is smaller and the porosity is higher; it is more conducive to hemostasis; further, the first network body includes: agarose; the second network body includes: bisacrylamide copolymer; the first network body and the second network body form a composite double network body; the first network body and the second network body form a composite double network structure; the mechanical properties of the hydrogel are greatly improved compared with a single network, especially the hydrogel has better toughness, which is more conducive to its composite with the oyster shell angelica polysaccharide complex; the hydrogel has better toughness, thereby greatly expanding the application range of the hydrogel; it can be suitable for various parts (such as hemostasis in non-flat areas such as joints); and because this composite hydrogel has a more excellent pore structure; it can stop bleeding faster (especially suitable for scenes with large bleeding).

[0033] Furthermore, in the above technical scheme, the oyster shell angelica polysaccharide complex contains a large amount of active calcium and antioxidant active ingredients, which is beneficial to hemostasis and can remove free radicals, improve antioxidant efficacy, and is beneficial to wound recovery; the oyster shell angelica polysaccharide complex is combined with the aforementioned composite double network body, which can greatly improve the hemostatic effect of the hydrogel while making the hydrogel have antioxidant properties, thereby improving the hemostatic effect while expanding the application field; for example, it can be expanded from the medical field to the beauty and skin care field.

[0034] Furthermore, in some embodiments of the present application, the loading amount of Angelica dahurica polysaccharide on the surface of the precipitate is 5% to 20%.

[0035] In the above technical scheme, the loading amount of Angelica dahurica polysaccharide on the surface of the sediment is 5% to 20%, which can effectively improve the dispersion effect of the oyster shell Angelica dahurica polysaccharide complex in the composite double network and avoid agglomeration, thereby effectively improving the pore size and porosity of the composite double network.

[0036] Illustratively, in some embodiments of the present application, the loading rate of Angelica dahurica polysaccharide on the surface of the precipitate is: 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% and 20% or a range between any two of the foregoing values.

[0037] In the above technical solution, "loading amount" has a well-known meaning in the art, which indicates the percentage of the substance loaded on the surface of the precipitate to the mass of the entire composite.

[0038] In the above technical scheme, the dispersion effect of the oyster shell angelica polysaccharide complex in the composite double network can be effectively improved to avoid agglomeration, thereby effectively improving the pore size and porosity of the composite double network.

[0039] Furthermore, in some embodiments of the present application, the second network body includes: a copolymer of lysine acrylamide, methacryloylethyl sulfobetaine, and methylenebisacrylamide.

[0040] In the above technical scheme, the copolymer of lysine acrylamide, methacryloylethyl sulfobetaine and methylene bisacrylamide can form a three-dimensional network structure with agarose as a double network structure; the mechanical properties are greatly improved compared with a single hydrogel, especially the hydrogel has better toughness, which is more conducive to its composite with oyster shell angelica polysaccharide microspheres; the hydrogel has better toughness, thereby greatly expanding the application range of the hydrogel; it can be suitable for various parts (such as hemostasis in non-flat areas such as joints); and because this composite hydrogel has a more excellent pore structure; it can stop bleeding faster (especially suitable for scenes with large bleeding).

[0041] Furthermore, in some embodiments of the present application, the percentage of the oyster shell angelica polysaccharide complex to the total mass of agarose, lysine acrylamide and methacryloylethyl sulfobetaine is 1% to 10%.

[0042] In the above technical solution, in the hydrogel, the percentage of the oyster shell angelica polysaccharide complex to the total mass of agarose, lysine acrylamide and methacryloylethyl sulfobetaine is 1% to 10%.

[0043] In the above technical scheme, in the hydrogel, the percentage of the oyster shell angelica polysaccharide complex relative to the total mass of agarose, lysine acrylamide and methacryloylethyl sulfobetaine is 1% to 10%; it can be well dispersed and evenly embedded in the composite double network, and is beneficial to the mechanical properties of the composite double network hydrogel, and can achieve the regulation of the pore size of the composite hydrogel, so that the pore size of the hydrogel is smaller and the porosity is higher; it is more conducive to hemostasis; thereby effectively improving the pore size and porosity of the composite double network.

[0044] Exemplarily, in some embodiments of the present application, in the hydrogel, the oyster shell angelica polysaccharide complex is 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10% or a range between any two of the foregoing values, measured as a percentage of the total mass of agarose, lysine acrylamide and methacryloylethyl sulfobetaine.

[0045] Some embodiments of the present application provide a method for preparing a hydrogel having hemostatic and antioxidant properties, comprising:

[0046] The oyster shell angelica polysaccharide complex is dispersed in the composite double network;

[0047] Wherein, the composite dual network body is formed by the first network body and the second network body;

[0048] The first network body includes: agarose; the second network body includes: bisacrylamide copolymer;

[0049] The preparation of the oyster shell and angelica polysaccharide complex comprises: reacting oyster shell materials with urea to obtain a precipitate; and coating the angelica polysaccharide on the surface of the precipitate.

[0050] In the above technical scheme, by dispersing the oyster shell angelica polysaccharide complex in the composite double network, a composite hydrogel of the oyster shell angelica polysaccharide complex and the composite double network can be obtained; the oyster shell angelica polysaccharide complex is dispersed in the composite double network structure, which effectively improves the pore structure of the composite hydrogel, reduces the pore size, and increases the porosity, which is beneficial to improving the hemostatic effect; at the same time, the mechanical properties of the composite hydrogel are enhanced, especially the toughness is improved, which is beneficial to expand the scope of use; at the same time, the oyster shell angelica polysaccharide complex is rich in active ingredients, so that the composite hydrogel also has antioxidant properties, further expanding the application field.

[0051] Further, in some embodiments of the present application, the oyster shell material is reacted with urea to obtain a precipitate, comprising:

[0052] The oyster shell material is mixed with phosphoric acid, citrate and urea to carry out a hydration reaction to obtain a precipitate.

[0053] In the above technical solution, the oyster shell material is reacted with urea to obtain a precipitate, comprising:

[0054] Oyster shell materials are mixed with phosphoric acid, citrate and urea to undergo hydration reaction to obtain a precipitate, which is conducive to the subsequent acquisition of an oyster shell and angelica polysaccharide complex uniformly coated with angelica polysaccharide, thereby facilitating the acquisition of a hydrogel structure with an excellent pore structure and more conducive to hemostasis.

[0055] Further, in some embodiments of the present application, the oyster shell material is reacted with urea to obtain a precipitate, comprising:

[0056] A weak acid solution of oyster shell material is mixed with 0.01mol / L-0.10mol / L phosphoric acid solution, 0.01mol / L-0.10mol / L citrate solution and 0.1mol / L-0.5mol / L urea solution to carry out a hydration reaction to obtain a precipitate, wherein the mass percentage of oyster shell material: phosphoric acid: citrate: urea is 5%-25%: 2%-15%: 2%-10%: 50%-90%.

[0057] For example, in some embodiments of the present application, oyster shell material is reacted with urea to obtain a precipitate, comprising:

[0058] According to the percentage by mass, 5%, 10%, 15%, 20%, 25% or the range between any two of the above values ​​of oyster shell material and the concentration of 0.01mol / L, 0.02mol / L, 0.03mol / L, 0.04mol / L, 0.04mol / L, 0.06mol / L, 0.07mol / L, 0.08mol / L, 0.09mol / L, 0.1mol / L or the range between any two of the above values ​​of phosphoric acid solution, concentration of 0.01mol / L, 0.02mol / L, 0.03mol / L, 0.04mol / L, 0.04mol / L, 0.06mol / L, 0.07mol / L, 0.08mol / L, 0.09mol / L, 0.1mol / L or the range between any two of the above values ​​of phosphoric acid solution. A citrate solution with a concentration of 0.01mol / L, 0.02mol / L, 0.03mol / L, 0.04mol / L, 0.04mol / L, 0.06mol / L, 0.07mol / L, 0.08mol / L, 0.09mol / L, 0.1mol / L or a range between any two of the aforementioned values, and a urea solution with a concentration of 0.01mol / L, 0.02mol / L, 0.03mol / L, 0.04mol / L, 0.04mol / L, 0.06mol / L, 0.07mol / L, 0.08mol / L, 0.09mol / L, 0.1mol / L or a range between any two of the aforementioned values, wherein the mass percentages of oyster shell material, phosphoric acid, citrate and urea are 5% to 25%, 2% to 15%, 2% to 10% and 50% to 90%, are mixed for hydration reaction to obtain a precipitate.

[0059] For example, in some embodiments of the present application, oyster shell material is reacted with urea to obtain a precipitate, comprising:

[0060] Calculated by mass percentage, oyster shell material is mixed with 0.08 mol / L phosphoric acid solution, 0.08 mol / L citrate solution and 0.08 mol / L urea solution, wherein the mass percentages of oyster shell material, phosphoric acid, citrate and urea are 7%:4%:3%:86%, and a hydration reaction is carried out to obtain a precipitate.

[0061] Further, in some embodiments of the present application, preparing oyster shell material includes:

[0062] The oyster shells are calcined to obtain a sintered product.

[0063] In the above technical solution, oyster shells are calcined to obtain a sintered material, which is beneficial to the subsequent preparation of oyster shell materials.

[0064] Further optionally, in some embodiments of the present application, the washed oyster shells are dried and crushed through a 50-150 mesh sieve to obtain oyster shell powder; the oyster shell powder is then calcined at 300°C to 400°C for 5 to 10 hours; a certain amount of the calcined oyster shell powder is weighed and dissolved in a 5% to 15% acetic acid solution, and the filtrate is filtered and collected.

[0065] For example, in some embodiments of the present application, the washed oyster shells are dried and crushed through a 50 mesh, 55 mesh, 58 mesh, 60 mesh, 65 mesh, 70 mesh, 75 mesh, 80 mesh, 85 mesh, 90 mesh, 95 mesh, 100 mesh, 105 mesh, 110 mesh, 120 mesh, 130 mesh, 140 mesh, 150 mesh sieve or a range between any two of the foregoing values ​​to obtain oyster shell powder; and then the oyster shell powder is sieved at 300°C, 310°C, 320°C, 330°C, 340°C, 350°C, 360°C, 370°C, 380°C, 390°C, 400°C, 410°C, 420°C, 430°C, 440°C, 450°C, 460°C, 470°C, 480°C, 490°C, 500°C 0°C, 350°C, 360°C, 370°C, 380°C, 390°C, 400°C or the range between any two of the aforementioned values, calcined for 5, 6, 7, 8, 9, 10 hours or the range between any two of the aforementioned values; weigh a certain amount of calcined oyster shell powder and dissolve it in an acetic acid solution with a concentration of 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15% or the range between any two of the aforementioned values, and filter and collect the filtrate.

[0066] Further, in some embodiments of the present application, the oyster shell angelica polysaccharide complex is dispersed in a composite double network, comprising:

[0067] The agarose solution is mixed with the oyster shell angelica polysaccharide complex to obtain a mixture; then lysine acrylamide, methacryloylethyl sulfobetaine, methylenebisacrylamide and ammonium persulfate are added to the mixture for reaction.

[0068] For example, in some embodiments of the present application, the oyster shell angelica polysaccharide complex is dispersed in a composite double network, comprising:

[0069] The agarose solution is mixed with the oyster shell angelica polysaccharide complex to obtain a mixture; then lysine acrylamide, methacryloylethyl sulfobetaine, methylenebisacrylamide and ammonium persulfate are added to the mixture for reaction.

[0070] For example, in some embodiments of the present application, the oyster shell angelica polysaccharide complex is dispersed in a composite double network, comprising:

[0071] A certain amount of agarose is weighed and added to deionized water so that the concentration of the agarose solution is 10 mg / mL to 50 mg / mL; the mixture is stirred at 90°C to 100°C for 20 min to 30 min until it is completely dissolved; the mixture is then cooled to 50°C to 60°C, and a polysaccharide complex of oyster shell angelica dahurica (relative to the total mass percentage of agarose, lysine acrylamide and methacryloylethyl sulfobetaine: 1% to 10%) is added, and the mixture is stirred thoroughly; 2.0 g of lysine acrylamide and methacryloylethyl sulfobetaine are added; Betaine (the percentage of methacryloylethyl sulfonyl betaine relative to the total mass of lysine acrylamide and methacryloylethyl sulfonyl betaine: 10% to 50%) is stirred until it is completely dissolved; 1 mg to 5 mg of methylenebisacrylamine is added and stirred evenly, and then 0.5 mL to 2 mL of ammonium persulfate solution (10 mg / mL to 30 mg / mL) is added, and after rapid stirring, the solution is poured into a mold, and reacted at 60° C. to 80° C. for 5 to 15 hours to obtain an agarose / oyster shell angelica polysaccharide composite hydrogel.

[0072] For example, in some embodiments of the present application, the oyster shell angelica polysaccharide complex is dispersed in a composite double network, comprising:

[0073] Weigh a certain amount of agarose and add it to deionized water to make the concentration of the agarose solution be 20 mg / mL, 21 mg / mL, 22 mg / mL, 23 mg / mL, 24 mg / mL, 25 mg / mL, 26 mg / mL, 27 mg / mL, 28 mg / mL, 29 mg / mL, 30 mg / mL, or a range between any two of the foregoing values; stir at 90°C, 91°C, 92°C, 92°C, 94°C, 95°C, 95°C, 95°C, 95°C, 95°C, and 100°C for 20 min, 21 min, 22 min, 23 min, 24 min, 25 min n, 26min, 27min, 28min, 29min, 30min or the range between any two of the above values; until completely dissolved; then cool to 50℃, 51℃, 52℃, 53℃, 54℃, 55℃, 56℃, 57℃, 58℃, 59℃, 60℃ or the range between any two of the above values; add a certain amount of oyster shell angelica polysaccharide complex and stir thoroughly; add a certain proportion of lysine acrylamide and methacryloylethyl sulfobetaine and stir until completely dissolved; add 1mg, 1.2mg, 1.5mg, 1.8mg, 2mg, 2.2mg, 2.5mg, 2 .8mg, 3mg, 3.2mg, 3.5mg, 3.8mg, 4mg, 4.2mg, 4.5mg, 4.8mg, 4.9mg, 5mg or the range between any two of the above values; after stirring methylenebispropyleneamine evenly, add 0.5mL, 0.6mL, 0.7mL, 0.9mL, 1mL, 1.2mL, 1.3mL, 1.5mL, 1.8mL, 1.9mL, 2mL or the range between any two of the above values; ammonium persulfate solution (10mg / mL, 12mg / mL, 15mg / mL, 18mg / mL, 20mg / mL, 22 ), quickly stirring the solution evenly and then pouring it into a mold, and reacting it at 60°C, 61°C, 62°C, 65°C, 68°C, 70°C, 72°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C or the range between any two of the aforementioned values; reacting it for 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 hours or the range between any two of the aforementioned values; thus obtaining agarose / oyster shell angelica polysaccharide composite hydrogel.

[0074] Furthermore, in some embodiments of the present application, a second colloid consisting of 5% to 15% agarose relative to the total mass percentage of lysine acrylamide, methacryloylethyl sulfobetaine and oyster shell angelica polysaccharide complex, 1% to 10% oyster shell angelica polysaccharide complex relative to the total mass percentage of agarose, lysine acrylamide and methacryloylethyl sulfobetaine, and 10% to 50% methacryloylethyl sulfobetaine relative to the total mass percentage of lysine acrylamide and methacryloylethyl sulfobetaine is mixed.

[0075] Illustratively, in some embodiments of the present application, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15% or agarose in the range between any two of the foregoing values, relative to the total mass percentage of lysine acrylamide, methacryloylethyl sulfobetaine and oyster shell angelica polysaccharide complex; 1%, 2%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10% or oyster shell angelica polysaccharide complex in the range between any two of the foregoing values, relative to the total mass percentage of agarose, lysine acrylamide and methacryloylethyl sulfobetaine; and a second colloid containing 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% or methacryloylethyl sulfobetaine in the range between any two of the foregoing values, relative to the total mass percentage of lysine acrylamide and methacryloylethyl sulfobetaine.

[0076] The features and performance of the present application are further described in detail below in conjunction with the embodiments:

[0077] Example 1

[0078] A hydrogel having hemostatic and antioxidant properties is provided, which is prepared according to the following steps:

[0079] 1. Preparation of Oyster Shell Angelica Polysaccharide Complex

[0080] First, the washed oyster shells were dried and crushed through a 100-mesh sieve, and then the oyster shell powder was calcined at 350°C for 8 hours; a certain amount of calcined oyster shell powder was weighed and dissolved in a 10% acetic acid solution, and the filtrate was collected by filtration; then, the collected filtrate was slowly added to a 0.06 mol / L phosphoric acid solution, and 0.08 mol / L sodium citrate solution and urea were added in sequence, and after stirring evenly, the mixture was transferred to a hydration reactor and reacted at 90°C for 40 hours. Finally, the mixture was centrifuged to collect a white precipitate, the precipitate was washed with deionized water and anhydrous ethanol, and dried in a vacuum oven at 60°C; 2 g of the dried white precipitate was weighed and added to 50 mL of a 10 mg / mL angelica polysaccharide solution, magnetically stirred at room temperature for 12 hours, the white precipitate was centrifuged and collected, and freeze-dried to obtain an oyster shell angelica polysaccharide complex.

[0081] 2. Preparation of agarose / oyster shell angelica polysaccharide composite hydrogel

[0082] A certain amount of agarose was weighed and added to 8 mL of deionized water, and stirred at 95 ° C for 30 min until completely dissolved; then the temperature was lowered to 55 ° C, a certain amount of oyster shell angelica polysaccharide complex was added, and it was fully stirred; a certain proportion of lysine acrylamide and methacryloylethyl sulfobetaine were added and stirred until completely dissolved; 3 mg of methylene bisacrylamide was added and stirred evenly, and then 1 mL of ammonium persulfate solution (20 mg / mL) was added, and the solution was quickly stirred and poured into a mold, and reacted at 70 ° C for 10 hours to obtain agarose / oyster shell angelica polysaccharide complex hydrogel;

[0083] Wherein: in the hydrogel sample, the percentage of agarose relative to the total mass of lysine acrylamide, methacryloylethyl sulfobetaine and oyster shell angelica polysaccharide complex: 5-15%

[0084] The percentage of methacryloylethyl sulfonyl betaine relative to the total mass of lysine acrylamide and methacryloylethyl sulfonyl betaine (the total mass of lysine acrylamide and methacryloylethyl sulfonyl betaine is 2.0 g): 10% to 50%;

[0085] The percentage of the oyster shell angelica polysaccharide complex relative to the total mass of agarose, lysine acrylamide and methacryloylethyl sulfobetaine is 1% to 10%; see Table 1 for details.

[0086] Examples 2-10, Comparative Examples 1-3

[0087] The difference from Example 1 is:

[0088] a The content ratio of agarose to lysine acrylamide, methacryloylethyl sulfobetaine and oyster shell angelica polysaccharide complex; b The percentage of methacryloylethyl sulfobetaine to the total mass of lysine acrylamide and methacryloylethyl sulfobetaine (the total mass of lysine acrylamide and methacryloylethyl sulfobetaine is 2.0 g); or c The percentage of oyster shell angelica polysaccharide complex to the total mass of agarose, lysine acrylamide and methacryloylethyl sulfobetaine; Not the same; See Table 1 for details.

[0089]

Performance test

[0090] 1. The pore structure of the hydrogels prepared in each embodiment and comparative example was detected using a scanning electron microscope.

[0091] Test results such as Figure 1 shown.

[0092] from Figure 1It can be seen that: compared with the comparative example sample, the pore structure of the example sample is more regular, and has mutually penetrating pore channels, and the pore wall thereof is embedded with spherical oyster shell angelica polysaccharide complex.

[0093] The pore structure of the hydrogel prepared in each embodiment is better than the pore structure of the hydrogel prepared in each comparative example; it can be seen that the hydrogel in the embodiment of the present application is more conducive to hemostasis.

[0094] Among them: the pore size of the example sample is significantly increased and has mutually penetrating pore channels, and the pore size of the hydrogel is about 50 μm to 200 μm, which is conducive to expanding the application field of the hydrogel.

[0095] 2. Test the mechanical properties of the above embodiments and comparative examples:

[0096] The mechanical properties of agarose / oyster shell angelica polysaccharide composite hydrogel were evaluated by tensile performance test as follows: the prepared hydrogel samples were cut into rectangular strips (20×6×3mm 3 ), and then use a universal testing machine to stretch the sample to break at a stretching rate of 100 mm / min, record the maximum force and maximum strain, and calculate the tensile strength and elongation at break of the hydrogel.

[0097] The test results are shown in Table 2.

[0098] 3. Evaluate the hemostatic performance of the above embodiments and comparative examples:

[0099] a. Prothrombin time (PT)

[0100] PT determination is an ideal and commonly used screening test for the exogenous coagulation system, and can also be used as a quantitative test for coagulation factors in the exogenous pathway and common pathway. First, citrate anticoagulated rabbit whole blood was centrifuged at 3000rpm for 5min at 4°C, and plasma was collected for later use. Weigh 1mg of sample and place it in a 2mL centrifuge tube, and weigh 3 parallels for each sample. Put the anticoagulated plasma, aerogel sample, and PT reagent in a 37°C water bath and incubate for 3min, then add 100μL plasma and 200μL PT reagent, start timing immediately, observe the coagulation of plasma, stop timing when the plasma appears lumpy and has no fluidity, and the recorded time is the prothrombin time. The centrifuge tube without aerogel sample was used as the blank control group.

[0101] The test results are shown in Table 3.

[0102] b. Activated partial thromboplastin time (APTT)

[0103] APTT assay is a relatively sensitive and commonly used screening test for the intrinsic coagulation system, and can also be used as a quantitative test for coagulation factors of the intrinsic pathway. First, citrate anticoagulated rabbit whole blood is centrifuged at 3000rpm for 5 minutes at 4°C, and plasma is collected for later use. Weigh 2mg of sample and place it in a 2mL centrifuge tube and preheat it at 37°C. Add 100μL of preheated plasma and 100μL APTT reagent and shake evenly; incubate in a 37°C water bath for 5 minutes, add 100μL of 0.025mol / L CaCl2 solution, and immediately start timing to observe the coagulation of plasma. Stop timing when the plasma appears lumpy and has no fluidity. The recorded time is the activated partial thromboplastin time.

[0104] The test results are shown in Table 3.

[0105] c. Whole blood coagulation test

[0106] Blood coagulation index (BCI) is an indicator used to evaluate the in vitro coagulation effect of materials. 3 The aerogel was placed in the middle of a culture dish with a diameter of 90 mm. 100 μL of citrate anticoagulated rabbit whole blood and 20 μL of 0.2 mol / L calcium chloride solution were dripped on the sample and allowed to stand for 5 minutes. Then 100 mL of deionized water was added and gently shaken to dissolve the incompletely coagulated blood. 100 μL was drawn into a 96-well plate and the absorbance was measured at a wavelength of 540 nm using an ELISA reader. The coagulation index (BCI, %) was calculated by the following formula: BCI (%) = As / Ac × 100%, where As represents the absorbance of the sample and Ac represents the absorbance of the control group. The sample without hydrogel was used as the control group.

[0107] The BCI test results are shown in Table 4.

[0108] d. Hemostatic performance test

[0109] The anesthetized mice were fixed on the surgical board. After removing the hair, the abdominal cavity of the mouse was gently cut open with a scalpel to fully expose the liver. The tissue fluid around the liver was completely absorbed by the gauze to reduce experimental interference. The weighed filter paper was placed under the liver, and then a wound of about 5 mm was cut on the liver with a scalpel to induce bleeding. The wound was hemostatically treated with agarose / oyster shell angelica polysaccharide complex hydrogel, and untreated mice were used as the control group. After hemostasis, the hemostasis time was recorded, and the filter paper weight was weighed to calculate the blood loss.

[0110] The test results are shown in Table 4.

[0111] 4. Evaluate the antioxidant properties of the above embodiments and comparative examples:

[0112] Antioxidant performance test steps:

[0113] The antioxidant behavior of the hydrogel was evaluated by DPPH free radical scavenging rate. 3 ) was soaked in 10 mL of distilled water for 24 hours; then, 3 mL of the soaking solution and 1 mL of DPPH / anhydrous ethanol solution (10 -3 mol / L) and reacted in the dark for 30 min; finally, the absorbance of the solution was measured at 517 nm using a UV-visible spectrophotometer. The DPPH free radical scavenging rate (DPPH, %) was calculated by the following formula:

[0114]

[0115] Among them, A DPPH is the absorbance of DPPH / anhydrous ethanol solution, A S It is the absorbance of the mixed solution of sample immersion solution and DPPH / anhydrous ethanol solution.

[0116] The test results are shown in Table 5.

[0117] Table 1 Feeding ratios of various examples and comparative examples during preparation;

[0118]

[0119] Notes: a The percentage of agarose to the total mass of lysine acrylamide, methacryloylethyl sulfobetaine and oyster shell angelica polysaccharide complex; b The percentage of methacryloylethyl sulfobetaine to the total mass of lysine acrylamide and methacryloylethyl sulfobetaine (the total mass of lysine acrylamide and methacryloylethyl sulfobetaine is 2.0 g); c The percentage of oyster shell angelica polysaccharide complex to the total mass of agarose, lysine acrylamide and methacryloylethyl sulfobetaine.

[0120] Table 2 Mechanical properties of hydrogels prepared in various embodiments and comparative examples

[0121] Hydrogel samples Tensile strength(KPa) Elongation at break (%) Comparative Example 1 13.7±2.0 115±12 Comparative Example 2 7.0±1.3 109±9 Comparative Example 3 50.2±2.7 161±12 Example 1 14.9±2.2 97±10 Example 2 16.6±2.6 97±16 Example 3 17.2±6.6 99±17 Example 4 21.6±2.9 68±4 Example 5 10.4±2.2 124±3 Example 6 62.2±1.9 124±7 Example 7 61.5±3 174±7 Example 8 70.5±6.2 160±24 Example 9 67±11.2 172±17 Example 10 86.5±6.3 146±16

[0122] From Table 2 we can see that:

[0123] For Comparative Example 1 without oyster shell angelica polysaccharide complex, its tensile strength and elongation at break were 13.7±2.0KPa and 115±12% respectively; as the content of oyster shell angelica polysaccharide complex increased, the tensile strength of Example 1, Example 2, Example 3 and Example 4 increased, and their elongation at break decreased. For Comparative Example 2 without agarose, its tensile strength and elongation at break were 7.0±1.3KPa and 109±9% respectively; as the content of agarose increased, the tensile strength and elongation at break of Examples 5 and 6 both increased. For Comparative Example 3 without methacryloylethyl sulfobetaine, its tensile strength and elongation at break were 50.2±2.7KPa and 161±12% respectively; as the content of methacryloylethyl sulfobetaine increased, the tensile strength of Examples 7 and 8 increased, and the elongation at break did not change significantly.

[0124] The mechanical properties of the hydrogels prepared in each embodiment are better than those of the hydrogels prepared in each comparative example;

[0125] The tensile strength of the embodiment is 10.4±2.2KPa to 86.5±6.3KPa, and the elongation at break is 68±4% to 174±7%. The tensile strength and elongation at break of the embodiment can be changed by adjusting the composition of the embodiment.

[0126] Table 3 PT and APPT test results of hydrogels prepared in various embodiments and comparative examples

[0127] Hydrogel samples PT(s) APPT(s) Control group 14.8±0.5 37.3±1.0 Comparative Example 1 12.3±0.5 36.9±0.5 Comparative Example 2 11.9±0.6 23.2±1.3 Comparative Example 3 12.2±2.2 25.0±1.7 Example 1 12.4±1.2 28.6±2.8 Example 2 12.9±1.9 25.2±1.6 Example 3 12.9±1.3 23.5±1.2 Example 4 14.5±2.1 21.7±0.7 Example 5 12.2±0.6 22.6±0.8 Example 6 12.7±2.2 21.2±2.4 Example 7 12.2±0.6 26.7±2.2 Example 8 10.9±0.3 21.4±2.0 Example 9 11.7±2.1 22.6±1.8 Example 10 11.0±1.6 21.2±1.6

[0128] From Table 3 we can see that:

[0129] The PT value of the control group was 14.8±0.5s; the PT values ​​of all comparative samples were 11.9±0.6s to 12.3±0.5s; and the PT values ​​of all example samples were 11.0±1.6 to 14.5±2.1s.

[0130] Among them, the PT values ​​of all comparative samples and example samples were slightly lower than those of the blank control group, and there was no significant difference between them and the blank control group, indicating that the agarose / oyster shell angelica polysaccharide complex hydrogel would not affect the prothrombin pathway.

[0131] Further, it can be seen from Table 3 that the APPT value of the control group is 37.3±1.0s; the APPT values ​​of all comparative samples are 23.2±1.3s to 36.9±0.5s; and the APPT values ​​of all example samples are 21.2±1.6s to 28.6±2.8s.

[0132] Among them, the APTT value of the sample was significantly lower than that of the blank control group, indicating that agarose / oyster shell angelica polysaccharide complex hydrogel has a significant procoagulant effect.

[0133] Table 4 BCI test results and hemostatic performance test results of the hydrogels prepared in various embodiments and comparative examples

[0134] Hydrogel samples BCI (%) Blood loss (g) Hemostasis time (s) Control group 100％ 0.342±0.037 106.8±10.0 Comparative Example 1 85.1±4.1 0.248±0.076 96.4±4.7 Comparative Example 2 79.9±3.7 0.268±0.031 97.0±8.2 Comparative Example 3 86.7±1.9 0.247±0.030 78.9±0.9 Example 3 82.6±7.2 0.236±0.058 76.3±6.1 Example 6 83.8±4.6 0.221±0.044 76.8±4.6 Example 9 81.4±6.8 0.229±0.067 77.2±7.4 Example 10 79.6±8.2 0.210±0.083 75.3±8.5

[0135] From Table 4 we can see that:

[0136] The BCI value of the control group is 100%; the BCI value of the comparative samples is 79.9±3.7% to 86.7±1.9%; and the BCI of the example samples is 79.2±8.2% to 83.8±4.6%.

[0137] The coagulation properties of the hydrogels prepared in each embodiment are better than those of the hydrogels prepared in each comparative example;

[0138] Among them, the BCI values ​​of all comparative examples and examples are significantly lower than that of the control group, and the BCI values ​​of the example samples are lower than those of the comparative examples. The BCI value of the example 10 sample is the smallest, which is 79.6±8.2%.

[0139] Furthermore, it can be seen from Table 4 that, relative to the comparative example samples, the blood loss and hemostasis time of all example samples are significantly smaller.

[0140] The coagulation performance of the hydrogels prepared in each embodiment is better than the hemostatic performance of the hydrogels prepared in each comparative example;

[0141] Among them, the hemostatic properties of the samples prepared in Comparative Example 1, Comparative Example 2, Comparative Example 3, Example 3, Example 6, Example 9 and Example 10 were evaluated using the liver hemostasis model, as shown in Table 4. The hemostatic amount and hemostatic time of mice treated with agarose / oyster shell angelica polysaccharide complex hydrogel were significantly less than those of the blank control group. The above results show that agarose / oyster shell angelica polysaccharide complex hydrogel has excellent hemostatic properties.

[0142] Table 5 Experimental results of antioxidant properties of agarose / oyster shell-Angelica polysaccharide composite hydrogel

[0143]

[0144]

[0145] From Table 5 we can see that:

[0146] The DPPH free radical scavenging rate of the control group (Angelica polysaccharide) was 12.2±2.8%. The DPPH free radical scavenging rates of the samples of Comparative Example 1, Comparative Example 2 and Comparative Example 3 were 9.2±1.2%, 17.8±2.5% and 12.6±1.4% respectively. The DPPH free radical scavenging rates of all the samples of the examples were 12.3±2.5% to 17.8±2.5%.

[0147] Among them, except for comparative example 1, the DPPH free radical scavenging rates of the other comparative examples and example samples were higher than those of the control group. Overall, the agarose / oyster shell angelica polysaccharide complex hydrogel has a good scavenging ability for DPPH free radicals. As the composition of the agarose / oyster shell angelica polysaccharide complex hydrogel changes, the antioxidant capacity changes.

[0148] The above description is only the preferred embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A hydrogel with hemostatic and antioxidant properties, characterized in that: The hydrogel comprises: Oyster shell angelica polysaccharide complex, a first network, a second network; the first network and the second network form a composite double network; the oyster shell angelica polysaccharide complex is dispersed in the composite double network; the first network includes: agarose; the second network includes: bisacrylamide copolymer; The oyster shell and angelica polysaccharide complex comprises: a precipitate formed by the reaction of oyster shell substances and urea; and angelica polysaccharide; and the angelica polysaccharide is coated on the surface of the precipitate.

2. The hydrogel having hemostatic and antioxidant properties according to claim 1, characterized in that: The loading amount of the Angelica dahurica polysaccharide on the surface of the precipitate is 5% to 20%.

3. The hydrogel having hemostatic and antioxidant properties according to claim 1, characterized in that: The second network body includes: a copolymer of lysine acrylamide, methacryloylethyl sulfobetaine and methylene bisacrylamide.

4. The hydrogel having hemostatic and antioxidant properties according to any one of claims 1 to 3, characterized in that: In terms of mass percentage, in the hydrogel, the percentage of the oyster shell angelica polysaccharide complex relative to the total mass of agarose, lysine acrylamide and methacryloylethyl sulfobetaine is 1% to 10%.

5. The hydrogel having hemostatic and antioxidant properties according to any one of claims 1 to 3, characterized in that: The average pore size of the hydrogel is 50 μm to 200 μm.

6. The method for preparing the hydrogel having hemostatic and antioxidant properties according to any one of claims 1 to 5, characterized in that: include: The oyster shell angelica polysaccharide complex is dispersed in the composite double network; Wherein, the composite dual network body is formed by a first network body and a second network body; The first network body comprises: agarose; the second network body comprises: bisacrylamide copolymer; The preparation of the oyster shell and angelica polysaccharide complex comprises: reacting oyster shell materials with urea to obtain a precipitate; and coating the angelica polysaccharide on the surface of the precipitate.

7. The method for preparing the hydrogel having hemostatic and antioxidant properties according to claim 6, characterized in that: include: The step of reacting oyster shell material with urea to obtain a precipitate comprises: The oyster shell material is mixed with phosphoric acid, citrate and urea to carry out a hydration reaction to obtain a precipitate.

8. The method for preparing the hydrogel having hemostatic and antioxidant properties according to claim 6, characterized in that: include: The preparation of the oyster shell material comprises: The oyster shells are calcined to obtain a sintered product.

9. The method for preparing the hydrogel having hemostatic and antioxidant properties according to claim 6, characterized in that: include: The method of dispersing the oyster shell angelica polysaccharide complex in the composite double network comprises: The agarose solution is mixed with the oyster shell angelica polysaccharide complex to obtain a mixture; then lysine acrylamide, methacryloylethyl sulfobetaine, methylenebisacrylamide and ammonium persulfate are added to the mixture for reaction.

10. The method for preparing the hydrogel having hemostatic and antioxidant properties according to claim 9, characterized in that: include: A second colloid is mixed which consists of 5% to 15% agarose relative to the total mass percentage of lysine acrylamide, methacryloylethyl sulfobetaine and oyster shell angelica polysaccharide complex, 1% to 10% oyster shell angelica polysaccharide complex relative to the total mass percentage of agarose, lysine acrylamide and methacryloylethyl sulfobetaine, and 10% to 50% methacryloylethyl sulfobetaine relative to the total mass percentage of lysine acrylamide and methacryloylethyl sulfobetaine.

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