A polyglutamic acid composite porous hydrogel, a preparation method and application thereof

Abstract

This invention provides a polyglutamic acid composite porous hydrogel, its preparation method, and its applications. Polyglutamic acid and polyvinyl alcohol aqueous solutions are mixed and crosslinked with glycidyl ether under alkaline and acidic conditions to form an interpenetrating network hydrogel. Calcium ions are then introduced to prepare a multifunctional composite hydrogel. The carboxyl groups on the polyglutamic acid molecular chain and the hydroxyl groups in the polyvinyl alcohol molecular structure can generate strong hydrogen bonds, further improving the mechanical strength of the hydrogel. Furthermore, the introduction of calcium ions (Ca) into the hydrogel network... 2+ This gives the hydrogel superior hemostatic properties.

Description

Technical Field

[0001] This invention belongs to the field of hydrogel materials, specifically relating to a polyglutamic acid composite porous hydrogel, its preparation method, and its application. Background Technology

[0002] Polyglutamic acid (γ-PGA) is a water-soluble anionic polymer formed by the polymerization of D-glutamic acid and L-glutamic acid through γ-glutamine bonds. Its side chains contain numerous free carboxyl groups, making it easily modifiable. As a biomedical polymer material, polyglutamic acid hydrogels possess advantages such as good biocompatibility, promotion of tissue repair and cell growth, non-toxic degradation products, good moisturizing effects, and strong adhesion. Therefore, they have wide applications in the medical field, including drug carriers, wound dressings, and surgical sutures.

[0003] Polyglutamic acid also has a certain hemostatic effect because its carboxyl group can react with ferrous ions (Fe2+) in the blood. 2+ It reacts to form a blood clot, sealing the wound and effectively stopping bleeding. Additionally, polyglutamic acid can chelate calcium ions (Ca). 2+ ), which makes it easy to achieve loading (Ca) during material preparation. 2+ Calcium ions, as hemostatic factors, can participate in intrinsic and extrinsic coagulation, accelerate fibrin formation, and thus promote blood clotting. Additionally, polyglutamic acid has strong adhesive properties, allowing it to bind tightly to tissues and seal wounds, achieving hemostasis. Summary of the Invention

[0004] To address the problems of existing technologies, this invention provides a polyglutamic acid hydrogel and its preparation method. Medical-grade polyglutamic acid and polyvinyl alcohol aqueous solutions are mixed, and then crosslinked with glycidyl ether under alkaline and acidic conditions to form an interpenetrating network hydrogel. Calcium ions (Ca) are then introduced. 2+ To prepare composite hydrogels with multiple functions.

[0005] One objective of this invention is to provide a polyglutamic acid composite porous hydrogel, comprising a cross-linked network structure of polyvinyl alcohol / polyglutamic acid and loaded calcium ions. Preferably, the cross-linked network structure of polyvinyl alcohol and polyglutamic acid comprises an interpenetrating network structure of polyvinyl alcohol and polyglutamic acid; the calcium ions (Ca... 2+ Carboxyl groups are loaded onto the framework structure of hydrogels through complexation.

[0006] In the above hydrogel, the mass ratio of polyvinyl alcohol to polyglutamic acid is 1:(0.5-50), preferably 1:(2-15). The calcium ion content in the hydrogel material is not particularly limited and can be adjusted according to actual needs.

[0007] In a preferred embodiment of the present invention, the hydrogel is obtained by crosslinking polyvinyl alcohol and polyglutamic acid sequentially under alkaline and acidic conditions, followed by loading calcium ions. The polyglutamic acid and polyvinyl alcohol form an interpenetrating network hydrogel by sequentially crosslinking under alkaline and acidic conditions using a chemical crosslinking agent, with calcium ions (Ca...) loaded onto the hydrogel. 2+ Carboxyl groups are loaded into the framework structure of hydrogels through complexation.

[0008] The second objective of this invention is to provide a method for preparing the above-mentioned polyglutamic acid composite porous hydrogel, comprising: mixing a polyvinyl alcohol solution and a polyglutamic acid solution, and then subjecting them to crosslinking reactions under alkaline and acidic conditions, followed by loading calcium ions to obtain the polyglutamic acid composite porous hydrogel.

[0009] In a preferred embodiment of the present invention, the preparation method specifically includes the following steps:

[0010] Step 1: Mix the polyvinyl alcohol solution and the polyglutamic acid solution, heat and stir until homogeneous to obtain a mixed solution;

[0011] Step 2: Add an alkaline regulator to adjust the solution to alkalinity, add a crosslinking agent, and heat to react;

[0012] Step 3: Add an acid regulator to adjust the solution to acidity, add a crosslinking agent, and heat to react and obtain polyglutamic acid hydrogel;

[0013] Step 4: Immerse the polyglutamic acid hydrogel obtained in step 3 in a soluble calcium salt solution, remove and dry it to obtain the polyglutamic acid composite porous hydrogel.

[0014] Specifically, in the above preparation method,

[0015] The polyvinyl alcohol is not particularly limited. Preferably, the number average molecular weight of the polyvinyl alcohol is 5 to 15W. The polyvinyl alcohol in this invention can be a commonly used commercial product, such as PVA17-88, PVA17-92, PVA17-99, etc.

[0016] The polyglutamic acid is not particularly limited, but preferably, the number average molecular weight of the polyglutamic acid is 5-200W, more preferably 70-100W.

[0017] The alkalinity adjuster is selected from at least one of sodium hydroxide solution, potassium hydroxide solution, ammonia water, and tris(hydroxymethyl)aminomethane hydrochloride buffer solution; the concentration of the alkaline solution used in the above alkalinity adjuster is not particularly limited, as long as it can adjust the solution to alkaline conditions. Preferably, the pH of the solution adjusted to alkaline is 8 to 10.

[0018] The crosslinking agents in step 2 or step 3 may be the same or different, and are independently selected from at least one of glycidyl ether compounds. The glycidyl ether is not particularly limited, but is preferably selected from at least one of ethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether, and butylene glycol diglycidyl ether.

[0019] The acidity regulator is selected from at least one of hydrochloric acid solution, dilute sulfuric acid solution, and citric acid solution; the concentration of the acid solution used in the above acidity regulator is not particularly limited, as long as it can adjust the solution to acidic conditions. Preferably, the pH of the solution is adjusted to acidic conditions to 3-6.

[0020] The soluble calcium salt is selected from at least one of calcium chloride, calcium gluconate, calcium acetate, and calcium lactate.

[0021] In a more preferred embodiment of the present invention, in step 1:

[0022] The concentration of the polyvinyl alcohol solution is 1-15 wt%, preferably 4-12 wt%.

[0023] The concentration of the polyglutamic acid solution is 5-60 wt%, preferably 20-50 wt%.

[0024] In the obtained mixed solution, the concentration of polyvinyl alcohol is 0.5-7.5 wt%, preferably 2-5 wt%; and the concentration of polyglutamic acid is 2.5-30 wt%, preferably 10-25 wt%.

[0025] In a more preferred embodiment of the present invention, in step 2:

[0026] In step 2, the heating temperature is 40–80°C and the heating time is 6–48 h; preferably, the heating temperature in step 2 is 45–65°C and the heating time is 10–24 h.

[0027] In terms of molar percentage, the molar amount of crosslinking agent in step 2 is 5-30% of the molar number of polyvinyl alcohol hydroxyl groups, preferably 10-20%.

[0028] In a more preferred embodiment of the present invention, in step 3:

[0029] In terms of molar percentage, the molar amount of crosslinking agent in step 3 is 2-30% of the molar number of polyglutamic acid carboxyl groups, preferably 5-10%;

[0030] In step 3, the heating temperature is 40–80°C and the heating time is 20–60 h; preferably, the heating temperature in step 3 is 45–65°C and the heating time is 40–48 h.

[0031] The polyglutamic acid hydrogel obtained in step 3 needs to be soaked in water. Preferably, the soaking treatment is to soak for 2 to 24 hours and soak 3 to 5 times.

[0032] In a more preferred embodiment of the present invention, in step 4:

[0033] The soluble calcium salt solution is preferably an aqueous solution of soluble calcium salt, with a concentration of 1–10 wt%, preferably 3–8 wt%.

[0034] The soaking time is 2 to 24 hours, preferably 3 to 10 hours;

[0035] The drying process is freeze drying. There are no specific limitations on the freeze drying equipment and drying conditions; any freeze drying method commonly used in this field can be used.

[0036] The third objective of this invention is to provide the above-mentioned polyglutamic acid composite porous hydrogel or the polyglutamic acid composite porous hydrogel obtained by the above preparation method for use in medical hemostatic materials.

[0037] This invention uses medical-grade polyglutamic acid and polyvinyl alcohol as raw materials, and diglycidyl ether as a crosslinking agent. Polyglutamic acid and polyvinyl alcohol are crosslinked under acidic and alkaline conditions to form an interpenetrating network hydrogel. In the preparation method of this invention, firstly, under alkaline conditions, the hydroxyl groups on the polyvinyl alcohol molecular chain react with the diglycidyl ether crosslinking agent to form a crosslinked structure. Because the concentration of polyvinyl alcohol in the mixed solution is low, the viscosity of the crosslinked system increases at this time, but a gel is not formed; it remains an unevenly dispersed mixed solution. Subsequently, the mixed solution is adjusted to acidic conditions, and the carboxyl groups on the polyglutamic acid molecular chain are crosslinked under acidic conditions by the diglycidyl ether crosslinking agent to form a three-dimensional network structure, making the mixed system of polyvinyl alcohol crosslinking product and polyglutamic acid crosslinking product an interpenetrating network hydrogel. Simultaneously, the carboxyl groups on the polyglutamic acid molecular chain and the hydroxyl groups in the polyvinyl alcohol molecular structure can generate strong hydrogen bonding, further improving the mechanical strength of the hydrogel. In addition, calcium ions (Ca) are introduced into the hydrogel network. 2+ This process gives the resulting gel multiple functions, resulting in superior hemostatic properties.

[0038] The beneficial effects of this invention are:

[0039] This invention provides a hydrogel loaded with calcium ions on an interpenetrating network structure of polyvinyl alcohol and polyglutamic acid. The interpenetrating network structure enhances the strength of the hydrogel material. Furthermore, the carboxyl groups on the polyglutamic acid molecular chain and the hydroxyl groups in the polyvinyl alcohol molecular structure can generate strong hydrogen bonds, further improving the mechanical strength of the hydrogel. The preparation method of the hydrogel material provided by this invention is simple and easy to implement, and the prepared hydrogel material exhibits excellent hemostatic properties and has broad application prospects. Attached Figure Description

[0040] Figure 1 This is a scanning electron microscope image of the hydrogel material obtained in Example 2.

[0041] Figure 2 The image shows a scanning electron microscope (SEM) image of the hydrogel material obtained in Comparative Example 1.

[0042] Figure 3 The image shows a scanning electron microscope (SEM) image of the hydrogel material obtained in Comparative Example 2.

[0043] from Figures 1-3 It can be seen from this that Figure 1 It is a composite hydrogel of polyvinyl alcohol and polyglutamic acid with a porous interconnected internal structure. Figure 2 It is a chemically cross-linked polyvinyl alcohol hydrogel with a porous internal structure, but the pores are basically not interconnected. Figure 3 It is a polyglutamic acid chemically cross-linked hydrogel with a porous internal structure and poor connectivity between pores.

[0044] Figure 4 The diagram shows the compression modulus of Examples 1-4, Comparative Examples 1 and 2. Figure 4 As can be seen, the compressive modulus of Examples 1-4 is much greater than that of Comparative Examples 1 and 2, indicating that the dual-network structure greatly improves the strength of the hydrogel. Detailed Implementation

[0045] The present invention will now be described in detail with reference to specific embodiments. It should be noted that the following embodiments are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the content of the present invention are still within the scope of protection of the present invention.

[0046] The raw materials used in the examples and comparative examples are readily available or prepared according to existing methods.

[0047] Methods for testing compressive modulus:

[0048] Take a cylindrical hydrogel wet sample (7 mm in diameter and 10 mm in height) prepared in the mold and apply pressure to the sample at a speed of 10 mm / min using an electronic universal testing machine at room temperature. Set the strain to 80% and record the compression modulus. Each sample should be tested at least five times.

[0049] Hydrogel in vitro coagulation time determination method:

[0050] Take 0.05g of the dry gels from Examples 1-4 and Comparative Examples 1-2, and 0.1mL of 0.01mol / L PBS solution (pH 7.4) to prepare suspensions of the above raw materials. Place each group of solutions in a glass test tube and incubate at 37°C for 2 minutes. Add 1mL of fresh whole blood drawn from the marginal ear vein of a New Zealand rabbit to each of the above mixtures and record the time immediately. After mixing thoroughly, continue incubation at 37°C. Tilt the glass test tube 90° every 10 seconds to observe whether the blood has coagulated until the blood has completely lost its fluidity, and record the coagulation time. Repeat each sample 6 times.

[0051] Example 1

[0052] Step 1: Add 10g of medical-grade polyvinyl alcohol (1788-L, molecular weight 85000) solid to 90g of deionized water, heat to 95℃, and stir thoroughly until completely dissolved. This solution is denoted as Solution A.

[0053] Step 2: Add 40g of medical-grade polyglutamic acid (molecular weight 1 million) solid to 60g of deionized water and stir thoroughly until completely dissolved. This solution is called solution B.

[0054] Step 3: At 50°C, mix solution A and solution B, stir until homogeneous, and adjust the pH of the mixed solution to 9 using a 20% sodium hydroxide aqueous solution.

[0055] Step 4: Add 4.4g of butanediol diglycidyl ether at 50℃, mix well, and react for 24h.

[0056] Step 5: After the reaction in Step 4 is completed, adjust the pH of the mixture to 5 with 5% acetic acid aqueous solution at 45℃, add 4.96g of ethylene glycol diglycidyl ether, and react for 40h.

[0057] Step 6: Soak the prepared hydrogel repeatedly in distilled water 3 times, immerse it in 5% CaCl2 aqueous solution for 5 hours, take it out and freeze dry to obtain polyglutamic acid composite porous hydrogel.

[0058] Example 2

[0059] Step 1: Add 6g of medical-grade polyvinyl alcohol (1792, molecular weight 60000) solid to 94g of deionized water, heat to 95℃, and stir thoroughly until completely dissolved. This solution is denoted as Solution A.

[0060] Step 2: Add 36g of medical-grade polyglutamic acid (molecular weight 900,000) solid to 64g of deionized water and stir thoroughly until completely dissolved. This solution is called solution B.

[0061] Step 3: Mix solution A and solution B at 55°C, stir until homogeneous, and adjust the pH of the mixed solution to 8.5 using Tris buffer.

[0062] Step 4: Add 3.2g of ethylene glycol diglycidyl ether at 55℃, mix well, and react for 20h.

[0063] Step 5: After the reaction in step 4 is completed, adjust the pH of the mixture to 4.6 with 20% dilute hydrochloric acid solution at 50°C, add 5g of butanediol diglycidyl ether, and react for 48h.

[0064] Step 6: Soak the prepared hydrogel repeatedly in distilled water 5 times, immerse it in 3% CaCl2 aqueous solution for 10 hours, take it out and freeze dry to obtain polyglutamic acid composite porous hydrogel.

[0065] Example 3

[0066] Step 1: Add 2g of medical-grade polyvinyl alcohol (1799, molecular weight 150000) solid to 48g of deionized water, heat to 95℃, and stir thoroughly until completely dissolved. This solution is denoted as Solution A.

[0067] Step 2: Add 25g of medical-grade polyglutamic acid (molecular weight 700,000) solid to 25g of deionized water and stir thoroughly until completely dissolved. This solution is called solution B.

[0068] Step 3: Mix solution A and solution B at 65°C, stir until homogeneous, and adjust the pH of the mixed solution to 9.5 with ammonia.

[0069] Step 4: Add 4.3g of polyethylene glycol diglycidyl ether (molecular weight 500) at 65℃, mix well, and react for 12h.

[0070] Step 5: After the reaction in Step 4 is completed, adjust the pH of the mixture to 3.5 with 10% citric acid aqueous solution at 65℃, add 6.5g of polyethylene glycol diglycidyl ether (molecular weight 500), and react for 42h.

[0071] Step 6: Soak the prepared hydrogel repeatedly in distilled water 5 times, immerse it in an 8% CaCl2 aqueous solution for 3 hours, and then freeze-dry it to obtain a polyglutamic acid composite porous hydrogel.

[0072] Example 4

[0073] Step 1: Add 5g of medical-grade polyvinyl alcohol (1788-L, molecular weight 80000) solid to 45g of deionized water, heat to 95℃, and stir thoroughly until completely dissolved. This solution is denoted as Solution A.

[0074] Step 2: Add 10g of medical-grade polyglutamic acid (molecular weight 800,000) solid to 40g of deionized water and stir thoroughly until completely dissolved. This solution is called solution B.

[0075] Step 3: Mix solution A and solution B at 60°C, stir until homogeneous, and adjust the pH of the mixed solution to 9.8 with a 20% potassium hydroxide aqueous solution.

[0076] Step 4: Add 4.3g of butanediol diglycidyl ether at 60℃, mix well, and react for 10h.

[0077] Step 5: After the reaction in step 4 is completed, adjust the pH of the mixture to 3.2 with 20% hydrochloric acid aqueous solution at 45℃, add 3.25g of polyethylene glycol diglycidyl ether (molecular weight 500), and react for 48h.

[0078] Step 6: Soak the prepared hydrogel repeatedly in distilled water 3 times, immerse it in 6% CaCl2 aqueous solution for 4.5 hours, take it out and freeze dry to obtain polyglutamic acid composite porous hydrogel.

[0079] Comparative Example 1

[0080] Step 1: Add 10g of medical-grade polyvinyl alcohol (1788-L, molecular weight 85000) solid to 90g of deionized water, heat to 95℃, and stir thoroughly until completely dissolved. This solution is denoted as Solution A.

[0081] Step 2: Add 40g of medical-grade polyglutamic acid (molecular weight 1 million) solid to 60g of deionized water and stir thoroughly until completely dissolved. This solution is called solution B.

[0082] Step 3: At 50°C, mix solution A and solution B, stir until homogeneous, and adjust the pH of the mixed solution to 9 using a 20% sodium hydroxide aqueous solution.

[0083] Step 4: At 50°C, add 4.4g of butylene glycol diglycidyl ether and 4.96g of ethylene glycol diglycidyl ether, mix well, and react for 48 hours.

[0084] Step 5: Soak the prepared hydrogel repeatedly in distilled water 3 times, immerse it in 5% CaCl2 aqueous solution for 5 hours, take it out and freeze dry to obtain the hydrogel of Comparative Example 1.

[0085] Comparative Example 2

[0086] Step 1: Add 10g of medical-grade polyvinyl alcohol (1788-L, molecular weight 85000) solid to 90g of deionized water, heat to 95℃, and stir thoroughly until completely dissolved. This solution is denoted as Solution A.

[0087] Step 2: Add 40g of medical-grade polyglutamic acid (molecular weight 1 million) solid to 60g of deionized water and stir thoroughly until completely dissolved. This solution is called solution B.

[0088] Step 3: At 50°C, mix solution A and solution B, stir well, and adjust the pH value to 3.5 with 20% hydrochloric acid solution.

[0089] Step 4: Add 9g of butanediol diglycidyl ether at 50℃, mix well, and react for 48h.

[0090] Step 5: Soak the prepared hydrogel repeatedly in distilled water 3 times, immerse it in 5% CaCl2 aqueous solution for 5 hours, take it out and freeze dry to obtain the hydrogel of Comparative Example 2.

[0091] The hydrogel materials obtained in Examples 1-4 and Comparative Examples 1-2 were subjected to in vitro coagulation time tests, and the test results are shown in Table 1.

[0092] Table 1 shows the results of in vitro coagulation time tests for Examples 1-4 and Comparative Examples 1-2.

[0093] Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Mean clotting time / s 32 35 30 58 Non-clotting blood 128

Claims

1. A polyglutamic acid composite porous hydrogel, comprising a cross-linked network structure of polyvinyl alcohol and polyglutamic acid, and loaded calcium ions, wherein the hydrogel is obtained by cross-linking polyvinyl alcohol and polyglutamic acid under alkaline and acidic conditions respectively and then loading calcium ions, wherein diglycidyl ether is used as a cross-linking agent.

2. The hydrogel according to claim 1, characterized in that: The cross-linked network structure of polyvinyl alcohol and polyglutamic acid includes an interpenetrating network structure of polyvinyl alcohol and polyglutamic acid; and / or, The calcium ions are loaded onto the framework structure of the hydrogel through the complexation of carboxyl groups.

3. The hydrogel according to claim 1, characterized in that, The mass ratio of polyvinyl alcohol to polyglutamic acid is 1:(0.5~50).

4. The hydrogel according to claim 3, characterized in that, The mass ratio of polyvinyl alcohol to polyglutamic acid is 1:(2~15).

5. A method for preparing the polyglutamic acid composite porous hydrogel according to any one of claims 1 to 4, comprising: After mixing polyvinyl alcohol solution and polyglutamic acid solution, crosslinking reaction was carried out sequentially under alkaline and acidic conditions, followed by loading calcium ions to obtain the polyglutamic acid composite porous hydrogel.

6. The preparation method according to claim 5, characterized in that, The preparation method specifically includes the following steps: Step 1: Mix the polyvinyl alcohol solution and the polyglutamic acid solution and stir until homogeneous to obtain a mixed solution; Step 2: Add an alkaline regulator to adjust the solution to alkalinity, add a crosslinking agent, and heat to react; Step 3: Add an acid regulator to adjust the solution to acidity, add a crosslinking agent, and heat to react and obtain polyglutamic acid hydrogel; Step 4: Immerse the polyglutamic acid hydrogel obtained in step 3 in a soluble calcium salt solution, remove and dry it to obtain the polyglutamic acid composite porous hydrogel.

7. The preparation method according to claim 6, characterized in that, The number-average molecular weight of the polyvinyl alcohol is 5-15W; and / or, The polyglutamic acid has a number-average molecular weight of 5-200 W; and / or, The alkalinity regulator is selected from at least one of sodium hydroxide solution, potassium hydroxide solution, ammonia, and tris(hydroxymethyl)aminomethane hydrochloride buffer; and / or, The crosslinking agents in step 2 or step 3 may be the same or different, and are independently selected from diglycidyl ether; and / or, The acid regulator is selected from at least one of hydrochloric acid solution, dilute sulfuric acid solution, and citric acid solution; and / or, The soluble calcium salt is selected from at least one of calcium chloride, calcium gluconate, calcium acetate, and calcium lactate.

8. The preparation method according to claim 7, characterized in that, The polyglutamic acid has a number-average molecular weight of 70-100 W; and / or, The crosslinking agents in step 2 or step 3 may be the same or different, and are independently selected from at least one of ethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether, and butylene glycol diglycidyl ether.

9. The preparation method according to claim 6, characterized in that, In step 1: The concentration of the polyvinyl alcohol solution is 1~15wt%; and / or, The concentration of the polyglutamic acid solution is 5-60 wt%; and / or, In the obtained mixed solution, the concentration of polyvinyl alcohol is 0.5~7.5wt% and the concentration of polyglutamic acid is 2.5~30wt%.

10. The preparation method according to claim 9, characterized in that, In step 1: The concentration of the polyvinyl alcohol solution is 4~12wt%; and / or, The concentration of the polyglutamic acid solution is 20-50 wt%; and / or, In the obtained mixed solution, the concentration of polyvinyl alcohol is 2-5 wt%, and the concentration of polyglutamic acid is 10-25 wt%.

11. The preparation method according to claim 6, characterized in that, In step 2: Adjust the solution to an alkaline pH of 8-10; and / or, The heating reaction is carried out at a temperature of 40-80°C for a duration of 6-48 hours; and / or, The molar amount of the crosslinking agent is 5 to 30% of the molar number of hydroxyl groups in polyvinyl alcohol, expressed as a molar percentage.

12. The preparation method according to claim 11, characterized in that, In step 2: The heating reaction is carried out at a temperature of 45-65°C for 10-24 hours; and / or, The molar amount of the crosslinking agent is 10 to 20% of the molar number of hydroxyl groups in polyvinyl alcohol, expressed as a molar percentage.

13. The preparation method according to claim 6, characterized in that, In step 3: Adjust the solution to an acidic pH of 3-6; and / or, The molar amount of the crosslinking agent, in molar percentage, is 2-30% of the molar number of polyglutamic acid carboxyl groups; and / or, The heating reaction is carried out at a temperature of 40-80°C for a duration of 20-60 hours; and / or, The polyglutamic acid hydrogel also needs to be soaked in water.

14. The preparation method according to claim 13, characterized in that, In step 3: The molar amount of the crosslinking agent, in molar percentage, is 5-10% of the molar number of polyglutamic acid carboxyl groups; and / or, The heating reaction is carried out at a temperature of 45~65℃ for a duration of 40~48 hours; and / or, The soaking treatment involves soaking for 2-24 hours, and repeating the soaking process 3-5 times.

15. The preparation method according to claim 6, characterized in that, In step 4: The concentration of the soluble calcium salt solution is 1~10 wt%; and / or, The soaking time is 2-24 hours; and / or, The drying process described is freeze-drying.

16. The preparation method according to claim 15, characterized in that, In step 4: The concentration of the soluble calcium salt solution is 3-8 wt%; and / or, The soaking time is 3 to 10 hours.

17. A polyglutamic acid composite porous hydrogel according to any one of claims 1 to 4, or a polyglutamic acid composite porous hydrogel obtained by the preparation method according to any one of claims 5 to 16, is applied to medical hemostatic materials.

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