A composite gel material for gingival hemostasis and its preparation method

Abstract

This invention discloses a composite gel material for gingival hemostasis and its preparation method, comprising the following components by weight: 0.8-1.2 parts ZnO@polylysine-modified curcumin, 1.0-1.5 parts sodium alginate, 0.6-1.0 parts gelatin, 0.3-0.5 parts ammonium bicarbonate, and 0.15-0.3 parts β-cyclodextrin. This invention utilizes the hydrophilic chains of polyamino acids and the hydrophobic chains of curcumin, combined with ZnO nanoparticles, to form a stable composite structure. This, along with the carrier structure formed by sodium alginate and gelatin, creates a porous hydrophilic network and rigid support. Hemostatic, coagulation, and swelling properties mutually promote each other, meeting the need for rapid fluid absorption from large-area bleeding wounds while also exhibiting strong adhesion and durability, making it suitable for the dynamic environment of oral chewing and saliva flushing.

Description

Technical Field

[0001] This invention belongs to the field of gel material technology, specifically referring to a composite gel material for gingival hemostasis and its preparation method. Background Technology

[0002] Gingival bleeding is one of the most common symptoms in clinical and daily oral care. Its causes include periodontal inflammation (gingivitis, periodontitis), mechanical injury (excessive brushing force, gingival tearing), and post-periodontal treatment (scaling, root planing, implant surgery). If bleeding is not stopped promptly or thoroughly, it can easily lead to complications such as wound infection, periodontal tissue recession, and hemorrhagic anemia, and in severe cases, it can even affect the progress of subsequent oral treatments. With increasing attention to oral health, the functional requirements for gingival hemostatic materials have evolved from simple rapid hemostasis to an integrated approach encompassing hemostasis, antibacterial properties, and repair. Traditional hemostatic materials have gradually revealed shortcomings such as limited functionality and poor environmental adaptability. Composite gel materials, due to their synergistic advantages across multiple components, have become a research hotspot in this field.

[0003] Currently, gingival hemostasis materials used in clinical and daily oral care are mainly divided into four categories, each with its own application limitations:

[0004] The first category consists of traditional natural polymer materials, represented by gelatin sponges, cellulose derivatives (such as sodium carboxymethyl cellulose), and alginate. These materials, with their good biocompatibility and absorbency, achieve hemostasis by physically adsorbing blood and activating platelet aggregation, making them widely used in cases of mild bleeding. However, these materials have significant drawbacks: weak resistance to saliva erosion, readily dissolving rapidly in the moist oral environment, resulting in hemostasis lasting less than 4 hours, making them unsuitable for persistent bleeding; poor adhesion, failing to adhere to the wound surface during dynamic oral activities (chewing, speaking), easily shifting and falling off; and a lack of antibacterial and tissue repair functions, providing only temporary hemostasis for inflammatory bleeding, failing to inhibit the growth of periodontal pathogens, and potentially causing foreign body inflammation due to material residue, thus prolonging wound healing. Furthermore, gelatin-based materials are mostly derived from animal tissues, posing a risk of immune allergies, and degradation products can easily affect the effectiveness of subsequent treatments such as resin bonding.

[0005] The second category consists of single bioactive materials, mainly including chitosan and its derivatives, thrombin, and zeolite. Chitosan, as a natural cationic polysaccharide, possesses both hemostatic and broad-spectrum antibacterial properties. The amino groups on its molecular chain can bind to anions on the surface of red blood cells, accelerating clot formation and simultaneously disrupting bacterial cell membrane structure to inhibit microbial growth. However, pure chitosan materials suffer from poor mechanical properties and rapid degradation in the acidic oral environment. Furthermore, its broad antibacterial spectrum can easily disrupt the balance of normal oral flora, and long-term use may induce bacterial resistance. Thrombin, as a highly efficient coagulation factor, can directly activate the coagulation cascade reaction, resulting in rapid hemostasis. However, it is expensive, has poor stability, is easily degraded by enzymes in saliva, and animal-derived thrombin poses a risk of cross-infection, limiting its clinical application. While inorganic hemostatic materials such as zeolite provide rapid hemostasis, they have poor biocompatibility, easily causing mucosal irritation, and are non-degradable, potentially leading to foreign body reactions in periodontal tissues if residues remain.

[0006] The third category consists of synthetic polymeric hemostatic materials, such as polyethylene glycol (PEG), polyurethane (PU), and polylactic-co-glycolic acid copolymer (PLGA). These materials possess good mechanical stability and biodegradability. By controlling the molecular structure, the swelling rate and degradation cycle of the material can be precisely matched to the needs of gingival restoration. However, synthetic polymeric materials themselves lack biological activity, and relying solely on physical sealing to achieve hemostasis results in a coagulation efficiency far lower than that of natural biological materials. Furthermore, some synthetic materials are excessively hydrophilic, easily swelling and disintegrating excessively in saliva, resulting in insufficient adhesion and difficulty in forming a stable hemostatic barrier on irregular wound surfaces. In addition, the biocompatibility of synthetic materials depends on molecular modification processes; materials that have not undergone surface modification may cause mucosal irritation or foreign body rejection reactions.

[0007] The fourth category consists of early composite hemostatic materials, which are mostly prepared by simply mixing natural polymers with antibacterial agents (such as silver ions and chlorhexidine) or coagulation active ingredients. Examples include chitosan-alginate composite sponges and gelatin-thrombin composite membranes, which to some extent compensate for the functional deficiencies of single materials. However, these composite materials still have significant shortcomings: First, poor compatibility between components leads to phase separation, resulting in unstable material structure and fluctuating hemostatic effects; second, insufficient functional synergy, with antibacterial agents often added directly without controlled release, leading to rapid loss and inability to achieve long-lasting antibacterial effects, and high concentrations of antibacterial agents may damage oral mucosal cells; third, poor adhesion and adaptability to the dynamic oral environment, lacking mechanical optimization for the high elasticity and susceptibility to mechanical stimulation of gingival tissue, still posing a risk of detachment; and fourth, insufficient ease of operation, as they are mostly sponge-like or membrane-like, making precise delivery to small gaps such as periodontal pockets difficult, and postoperative cleaning is inconvenient, with residues potentially affecting subsequent treatment. Summary of the Invention

[0008] To address the above issues and overcome the shortcomings of existing technologies, this invention provides a composite gel material for gingival hemostasis and its preparation method. This invention combines the hydrophilic chains of polyamino acids and the hydrophobic chains of curcumin with ZnO nanoparticles to form a stable composite structure. Combined with a carrier structure formed by sodium alginate and gelatin, it creates a porous, hydrophilic, interpenetrating network and rigid support. The hemostatic, coagulation, and swelling properties mutually promote each other, meeting the rapid absorption needs of large-area bleeding wounds while also exhibiting strong adhesion and durability, making it suitable for the dynamic environment of oral chewing and saliva flushing.

[0009] To achieve the above objectives, the technical solution adopted by the present invention is as follows: The present invention proposes a composite gel material for gingival hemostasis, the composite gel material comprising the following components in parts by weight: 0.8-1.2 parts ZnO@polylysine modified curcumin, 1.0-1.5 parts sodium alginate, 0.6-1.0 parts gelatin, 0.3-0.5 parts ammonium bicarbonate, and 0.15-0.3 parts β-cyclodextrin;

[0010] Preferably, the preparation method of the ZnO@polylysine modified curcumin specifically includes the following steps:

[0011] S1. Dissolve 4-bromo-3-methoxybenzaldehyde in anhydrous ethanol, add acetylacetone, mix well, add tributyl borate and piperidine to the reaction system, raise the reaction temperature to carry out reflux reaction, after the reaction is completed, cool, remove excess organic solvent by rotary evaporation, purify and dry to obtain bromosubstituted curcumin.

[0012] Preferably, in step S1, the mass-to-volume ratio of 4-bromo-3-methoxybenzaldehyde to acetylacetone is 2.2-2.7 g: 0.5-0.7 mL;

[0013] Preferably, in step S1, the volume ratio between tributyl borate and acetylacetone is 0.13-0.18:1;

[0014] Preferably, in step S1, the volume ratio between piperidine and acetylacetone is 1-1.2:1;

[0015] Preferably, in step S1, the reflux reaction temperature is 75-85°C, and the reflux reaction time is 6-8 hours.

[0016] S2. Dissolve anhydrous potassium carbonate in anhydrous DMF, add Boc-L-lysine, and stir until the reactants are completely dissolved. Then, dissolve the bromo-substituted curcumin prepared in step S1 in anhydrous DMF and add it dropwise to the reaction system through a constant pressure dropping funnel. After mixing evenly, raise the reaction temperature to carry out the substitution reaction. After the reaction is completed, cool and add ice water to quench the reaction. Add ethyl acetate for multiple extractions, collect the organic phase, wash with saturated sodium chloride solution, dry the washed organic phase with anhydrous sodium sulfate, concentrate under reduced pressure to remove organic solvent, purify and dry to obtain Boc-lysine-modified curcumin.

[0017] Preferably, in step S2, the mass ratio of Boc-L-lysine to anhydrous potassium carbonate is 2.0-2.5:0.3-0.4;

[0018] Preferably, in step S2, the mass ratio of the brominated curcumin to Boc-L-lysine is 1.9-2.5:2.0-2.5;

[0019] Preferably, in step S2, the reaction temperature of the substitution reaction is 70-80°C, and the reaction time of the substitution reaction is 12-16 h;

[0020] S3. Dissolve the Boc-lysine-modified curcumin prepared in step S2 in anhydrous DCM, transfer it to an ice-water bath for thorough cooling, slowly add trifluoroacetic acid dropwise to the reaction system, after the addition is complete, carry out the deprotection reaction at room temperature, add triethylamine to neutralize the reaction system, remove excess solvent and reactants by vacuum distillation, add anhydrous diethyl ether to precipitate the precipitate, filter, collect the filtrate, concentrate under vacuum to obtain lysine-modified curcumin;

[0021] Preferably, in step S3, the mass-to-volume ratio of Boc-L-lysine to trifluoroacetic acid in step S2 is 2.0-2.5g:6-7.5mL;

[0022] Preferably, in step S3, the stirring speed of the deprotection reaction is 200-400 rpm, and the deprotection reaction time is 1.5-2.5 h;

[0023] S4. Dissolve EDC·HCl (1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride) and HOBt (1-hydroxybenzotriazole) in anhydrous DCM. Purge with flowing nitrogen gas. Dissolve the lysine-modified curcumin prepared in step S3 in anhydrous DCM and add it dropwise to the reaction system. After mixing evenly, slowly add DIPEA (N,N-diisopropylethylamine) to the reaction system. Perform the polymerization reaction at room temperature. After the reaction is completed, slowly add anhydrous diethyl ether at 4°C to the reaction system. After the precipitate precipitates, filter and collect the precipitate. Wash with anhydrous diethyl ether, dissolve in deionized water for dialysis purification, and freeze-dry to obtain polylysine-modified curcumin.

[0024] Preferably, in step S4, the mass ratio of lysine-modified curcumin, EDC·HCl and HOBt is 1.6-1.9:1.8-2.2:1.55-1.65;

[0025] Preferably, in step S4, the mass-to-volume ratio between the lysine-modified curcumin and DIPEA is 0.47-0.53 g / mL;

[0026] Preferably, in step S4, the stirring speed of the polymerization reaction is 300-400 rpm, and the reaction time of the polymerization reaction is 36-48 h;

[0027] S5. Dissolve the polylysine-modified curcumin prepared in step S4 in an ethanol aqueous solution. Dissolve zinc acetate dihydrate and zinc nitrate hexahydrate in an ethanol aqueous solution and slowly add them dropwise to the reaction system. Carry out the complexation reaction at room temperature. After the reaction is completed, add ammonia aqueous solution dropwise to the reaction system to adjust the pH of the reaction to 7.5-8.0. After mixing evenly, raise the temperature to carry out the mineralization reaction. After the reaction is completed, cool the system and place it in deionized water for dialysis. After freeze-drying, ZnO@polylysine-modified curcumin is obtained.

[0028] Preferably, in step S5, the mass ratio of zinc acetate dihydrate to zinc nitrate hexahydrate is 0.055-0.08:0.075-0.12;

[0029] Preferably, in step S5, the mass ratio between the total amount of polylysine-modified curcumin and zinc acetate dihydrate and zinc nitrate hexahydrate is 1.4-1.7:0.13-0.185;

[0030] Preferably, in step S5, the stirring speed of the complexation reaction is 300-500 rpm, and the complexation reaction time is 2-4 h;

[0031] Preferably, in step S5, the reaction temperature of the mineralization reaction is 50-60℃, and the reaction time of the mineralization reaction is 6-8h;

[0032] This invention also provides a method for preparing a composite gel material for gingival hemostasis, specifically including the following steps:

[0033] ① Take ZnO@polylysine modified curcumin and β-cyclodextrin and place them in deionized water. Sonicate them at 250-400W power for 15-30 minutes to obtain the first dispersion.

[0034] ② Place sodium alginate and gelatin in deionized water, raise the temperature to fully dissolve the reactants, and then add the first dispersion prepared in step ① dropwise to the reaction system. Stir at a speed of 500-600 rpm until fully dispersed to obtain a suspension.

[0035] ③ Take the suspension prepared in step ②, add ammonium bicarbonate to it, stir at 400-500 rpm for 10-15 min, transfer it to a mold, place it under constant temperature conditions to carry out the pore-forming reaction, after the reaction is completed, add calcium chloride solution to carry out the cross-linking reaction, wash, freeze dry, demold, cut, sterilize, and obtain the composite gel material.

[0036] The beneficial effects achieved by this invention are as follows:

[0037] This invention provides a composite gel material for gingival hemostasis and its preparation method. The invention combines the hydrophilic chains of polyamino acids and the hydrophobic chains of curcumin with ZnO nanoparticles to form a stable composite structure. Combined with the carrier structure formed by sodium alginate and gelatin, a porous hydrophilic intertransmission network and rigid support are formed. The hemostatic, coagulation and swelling properties are mutually promoted. It not only meets the need for rapid fluid absorption of large-area bleeding wounds, but also has the characteristics of strong adhesion and durability, and is suitable for the dynamic environment of oral chewing and saliva flushing. In this invention, 4-bromo-3-methoxybenzaldehyde and acetylacetone are used as raw materials. Under the synergistic effect of tributyl borate and piperidine, a directional bimolecular aldol condensation reaction occurs to form bromosubstituted curcumin containing a β-diketone structure. The β-diketone structure of curcumin is a key site for subsequent activation of coagulation factors VII / IX, laying the molecular foundation for coagulation function. The aromatic ring hydrophobic chain enhances the stability of blood clots through intermolecular forces. The hydrophobic aromatic ring provides structural support for subsequent hydrophilic-hydrophobic synergy, avoiding gel collapse caused by excessive water absorption during subsequent swelling. The anti-inflammatory activity of curcumin itself can alleviate wound inflammation, indirectly reducing bleeding and assisting in hemostasis. The introduced lysine unit contains an amino group, which can electrostatically adsorb with the anion membranes of erythrocytes and platelets, promoting platelet adhesion and aggregation. The hydrophilic amino group of the lysine unit provides a basis for subsequent polymerization into chains. Providing hydrophilic sites lays the foundation for the sponge's high absorbency. The ε-amino group of lysine can bind to coagulation factors, accelerating prothrombin activation and shortening clotting time. The hydrophilic polylysine chains (containing a large number of -NH2 / -COOH groups) form a hydrophilic network, rapidly adsorbing water through hydrogen bonds and electrostatic interactions, increasing the gel's absorbency. Simultaneously, the flexibility of the polymer chains provides support for the elasticity of the structure after swelling. Multiple composite cationic amino sites form an electrostatic adsorption network, efficiently capturing platelets and red blood cells, accelerating blood clot formation. The entanglement of polymer chains enhances the mechanical stability of the blood clot, preventing detachment. Lysine units on the polymer chains can bind to coagulation factors at multiple sites, forming a concentrated microenvironment for coagulation factors, shortening prothrombin time and activated partial thromboplastin time. The curcumin β-diketone group of polylysine-modified curcumin reacts with Zn... 2+ (From zinc acetate dihydrate / zinc nitrate hexahydrate) forming a chelate complex, ammonia water is added dropwise to adjust the pH to 7.5, Zn at 50℃ 2+ Slow mineralization generates ZnO nanonuclei, forming a ZnO core-polylysine-curcumin shell structure. The high specific surface area of ​​the ZnO nanonuclei physically adsorbs coagulation factors, concentrates coagulation components, and accelerates blood clot formation; Zn 2+Slow release can activate clotting factors and further shorten clotting time. The rigid structure of the ZnO core provides physical support for the sponge, preventing pore collapse during swelling. The hydrophobic core-hydrophilic shell design of the core-shell structure balances the liquid absorption rate and structural stability, preventing excessive swelling. The ROS effect of ZnO can slightly disrupt bacterial cell membranes, reducing secondary bleeding caused by infection. The slow release characteristic of the core-shell structure prolongs the action time of hemostatic components. In this invention, β-cyclodextrin stabilizes curcumin, ensuring its coagulation factor activation function is not lost; uniform particle distribution allows hemostatic / coagulation components to exert their effects throughout the sponge, avoiding uneven local effects; sodium alginate and gelatin form a three-dimensional network through hydrogen bonding and electrostatic interactions; the polylysine hydrophilic segment of ZnO@core-shell particles forms a synergistic hydrophilic network with the carrier, while the hydrophobic segment of curcumin structure is embedded in the network to provide rigid support; the carboxyl groups of sodium alginate form strong hydrogen bonds with water molecules, which is beneficial for improving liquid absorption performance; the flexible segments of gelatin enhance the elasticity of the sponge after swelling, preventing brittle fracture; the cation binding sites of sodium alginate can assist in the adsorption of platelets, synergizing with the hemostatic function of the core-shell particles; the carrier network rapidly absorbs liquid, concentrates coagulation components in the blood, and accelerates... For hemostasis, gelatin itself is a natural coagulation promoter that can activate prothrombin, which, combined with the coagulation function of core-shell particles, further shortens PT (prothrombin time) and APTT (activated partial thromboplastin time). The thermal decomposition of ammonium bicarbonate produces CO2 / NH3, forming interconnected pores that provide channels for rapid water penetration. The pore size matches the size of blood cells, ensuring rapid liquid absorption while retaining coagulation components. The cross-linked structure prevents gel collapse after swelling, balancing liquid absorption and structural stability. The porous structure increases the contact area with the wound, preventing saliva from washing it off. Its high absorbency rapidly absorbs large amounts of blood, reducing wound bleeding. The porous structure concentrates coagulation factors, creating a localized high-concentration coagulation microenvironment and accelerating clot formation. Attached Figure Description

[0038] Figure 1 The swelling ratio results are shown in the figures for the composite gel materials prepared in Examples 1-3 and Comparative Examples 1-3 of this invention.

[0039] Figure 2 The graph shows the coagulation performance results of the composite gel materials prepared in Examples 1-3 and Comparative Examples 1-3 of this invention.

[0040] Figure 3 The images show the clotting time results of the composite gel materials prepared in Examples 1-3 and Comparative Examples 1-3 of this invention.

[0041] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof. Detailed Implementation

[0042] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0043] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application.

[0044] Unless otherwise specified, the experimental methods used in the following examples are conventional methods; unless otherwise specified, the experimental materials and test strains used in the following examples were purchased from commercial channels.

[0045] Example 1

[0046] This embodiment provides a composite gel material for gingival hemostasis, the composite gel material comprising the following components in parts by weight: 0.8 parts ZnO@polylysine modified curcumin, 1.0 part sodium alginate, 0.6 parts gelatin, 0.3 parts ammonium bicarbonate, and 0.15 parts β-cyclodextrin;

[0047] The preparation method of ZnO@polylysine modified curcumin specifically includes the following steps:

[0048] S1. Accurately weigh 2.2 g of 4-bromo-3-methoxybenzaldehyde and place it in a flask. Add 50 mL of anhydrous ethanol and completely dissolve the 4-bromo-3-methoxybenzaldehyde. Then, dissolve 0.5 mL of acetylacetone in 5 mL of anhydrous ethanol and add it to the reaction system. After mixing evenly, add 0.090 mL of tributyl borate and 0.060 mL of piperidine to the reaction system. Stir at 200 rpm to form a homogeneous reaction system. Raise the reaction temperature to 75 °C and react for 8 h. After the reaction is complete, remove excess reaction solvent by rotary evaporation. After recrystallization purification, dry under vacuum at 40 °C for 6 h to obtain bromosubstituted curcumin.

[0049] S2. Place 0.3g of anhydrous potassium carbonate in a flask, add 50mL of anhydrous DMF to dissolve the potassium carbonate, add 2.0g of Boc-L-lysine to the flask, stir at 300rpm, raise the reaction temperature to 30℃, and stir the reactants until completely dissolved. Take 1.9g of the bromosubstituted curcumin prepared in step S1 and dissolve it in 10mL of anhydrous DMF. Add it to the reaction system through a constant pressure dropping funnel at a rate of 1 drop / s. Continue stirring and mixing until uniform. Raise the reaction temperature to 70℃ to carry out the substitution reaction. After the reaction is completed, after the reaction system is cooled to room temperature, add ice water to quench the reaction. Add ethyl acetate for multiple extractions, collect the organic phase, wash with saturated sodium chloride solution, remove water and dry the washed organic phase with anhydrous sodium sulfate, concentrate under reduced pressure to remove organic solvent, purify and dry to obtain Boc-lysine modified curcumin.

[0050] S3. Take the Boc-lysine modified curcumin prepared in step S2 and place it in a flask. Add 80 mL of anhydrous DCM to completely dissolve it. Transfer the reaction system to an ice-water bath for sufficient cooling. Dissolve 6 mL of trifluoroacetic acid in 20 mL of anhydrous DCM and slowly add it dropwise to the reaction system at a rate of 1 mL / min. At the same time, stir the reaction at a rate of 300 rpm. After the addition is complete, remove the ice-water bath and carry out the deprotection reaction at room temperature. After 2 hours, add triethylamine dropwise to adjust the pH of the reaction to 7.5. Add anhydrous diethyl ether and stir the reaction. Remove excess solvent and reactants by vacuum distillation. After adding anhydrous diethyl ether to precipitate the precipitate, filter it, collect the filtrate, concentrate it under vacuum, and obtain lysine modified curcumin.

[0051] S4. Accurately weigh 1.8g of EDC·HCl and 1.65g of HOBt and dissolve them in 50mL of anhydrous DCM. After completely replacing the air in the reaction system with flowing nitrogen, dissolve 1.6g of the lysine-modified curcumin prepared in step S3 in 50mL of anhydrous DCM and add it to the reaction system at a rate of 1mL / min while stirring at 300rpm. After mixing evenly, add 3mL of DIPEA to the reaction system at a rate of 1 drop / s and continue stirring. The polymerization reaction is carried out at room temperature for 36h. After the reaction is completed, anhydrous diethyl ether at 4℃ is slowly added to the reaction system. After the precipitate precipitates, filter it, collect the precipitate, wash it with anhydrous diethyl ether, dissolve it in deionized water, transfer it to a pretreated dialysis bag (3000Da), dialyze it in 500mL of deionized water for 24h, and freeze-dry it to obtain polylysine-modified curcumin.

[0052] S5. Place 1.4 g of the polylysine-modified curcumin prepared in step S4 into a three-necked flask, and add 30 mL of ethanol aqueous solution (V). 乙醇:V 水 =3:2), after fully dispersing by stirring at 200 rpm, dissolve 55 mg of zinc acetate dihydrate and 75 mg of zinc nitrate hexahydrate in 20 mL of ethanol aqueous solution (V 乙醇 :V 水 In a 3:2 ratio, ZnO was added dropwise to the reaction system at a rate of 1 mL / min, and stirred at 300 rpm. The complexation reaction was carried out at room temperature for 4 h. After the reaction was completed, 1 mol / L ammonia solution was added dropwise to the reaction system to adjust the pH to 7.5. After mixing evenly, the temperature of the reactants was raised to 50 °C to carry out the mineralization reaction for 8 h. After the reaction was completed, the reaction system was cooled to room temperature, and the reaction solution was transferred to a dialysis bag (5000 Da). Dialysis was performed with deionized water for 24 h. After dialysis, the solution was transferred to a centrifuge tube, centrifuged at 8000 rpm for 10 min, and the precipitate was collected. The precipitate was washed three times with anhydrous ethanol and freeze-dried to obtain ZnO@polylysine modified curcumin.

[0053] This embodiment also provides a method for preparing a composite gel material for gingival hemostasis, specifically including the following steps:

[0054] ① Take 0.8g of ZnO@polylysine modified curcumin and 0.15g of β-cyclodextrin and place them in 20mL of deionized water. Sonicate at 250W for 30min to obtain the first dispersion.

[0055] ② Take 1.0g of sodium alginate and 0.6g of gelatin and place them in 20mL of deionized water. After the reactants are fully dissolved by raising the temperature to 40℃, add the first dispersion prepared in step ① dropwise to the reaction system and stir at 500rpm. After being fully dispersed, a suspension is obtained.

[0056] ③ Take the suspension prepared in step ②, add 0.3g of ammonium bicarbonate to it, stir at 400rpm for 15min, transfer to a mold, and place it at a constant temperature of 37℃ for pore formation reaction for 30min. After the reaction, add 20mL of calcium chloride solution for cross-linking reaction. After 15min, take out the gel, wash it 3 times with deionized water, then wash it 2 times with anhydrous ethanol, squeeze the sponge to remove excess liquid, and pre-freeze it in a -50℃ ultra-low temperature freezer for 4h. Transfer it to a freeze dryer, set the vacuum degree to ≤10Pa, and freeze-dry for 24h. After freeze-drying, take it out, demold it, and cut it according to the wound size. Place it in a sterile packaging bag and sterilize it with γ-rays to obtain the composite gel material. After sterilization, seal and store it.

[0057] Example 2

[0058] This embodiment provides a composite gel material for gingival hemostasis, the composite gel material comprising the following components in parts by weight: 1.0 part ZnO@polylysine modified curcumin, 1.2 parts sodium alginate, 0.8 parts gelatin, 0.4 parts ammonium bicarbonate, and 0.23 parts β-cyclodextrin;

[0059] The preparation method of ZnO@polylysine modified curcumin specifically includes the following steps:

[0060] S1. Accurately weigh 2.5 g of 4-bromo-3-methoxybenzaldehyde and place it in a flask. Add 50 mL of anhydrous ethanol and completely dissolve the 4-bromo-3-methoxybenzaldehyde. Then, dissolve 0.6 mL of acetylacetone in 5 mL of anhydrous ethanol and add it to the reaction system. After mixing evenly, add 0.095 mL of tributyl borate and 0.065 mL of piperidine to the reaction system. Stir at 200 rpm to form a homogeneous reaction system. Raise the reaction temperature to 80 °C and react for 7 h. After the reaction is complete, remove excess reaction solvent by rotary evaporation. After recrystallization purification, dry under vacuum at 40 °C for 6 h to obtain bromosubstituted curcumin.

[0061] S2. Place 0.35g of anhydrous potassium carbonate in a flask, add 50mL of anhydrous DMF to dissolve the potassium carbonate, add 2.3g of Boc-L-lysine to the flask, stir at 300rpm, raise the reaction temperature to 30℃, and stir the reactants until completely dissolved. Take 2.2g of the bromosubstituted curcumin prepared in step S1 and dissolve it in 10mL of anhydrous DMF. Add it to the reaction system through a constant pressure dropping funnel at a rate of 1 drop / s. Continue stirring and mixing until uniform. Raise the reaction temperature to 75℃ to carry out the substitution reaction. After the reaction is completed, after the reaction system is cooled to room temperature, add ice water to quench the reaction. Add ethyl acetate for multiple extractions, collect the organic phase, wash with saturated sodium chloride solution, remove water and dry the washed organic phase with anhydrous sodium sulfate, concentrate under reduced pressure to remove organic solvent, purify and dry to obtain Boc-lysine modified curcumin.

[0062] S3. Place the Boc-lysine-modified curcumin prepared in step S2 into a flask, add 80 mL of anhydrous DCM to completely dissolve it, transfer the reaction system to an ice-water bath for sufficient cooling, dissolve 7 mL of trifluoroacetic acid in 20 mL of anhydrous DCM, and slowly add it dropwise to the reaction system at a rate of 1 mL / min while stirring at 200 rpm. After the addition is complete, remove the ice-water bath and carry out the deprotection reaction at room temperature. After 2.5 h, add triethylamine dropwise to adjust the pH of the reaction to 7.5, add anhydrous diethyl ether and stir the reaction, remove excess solvent and reactants by vacuum distillation, add anhydrous diethyl ether to precipitate the precipitate, filter, collect the filtrate, concentrate under vacuum to obtain lysine-modified curcumin;

[0063] S4. Accurately weigh 2.0 g of EDC·HCl and 1.6 g of HOBt and dissolve them in 50 mL of anhydrous DCM. After completely replacing the air in the reaction system with flowing nitrogen, dissolve 1.8 g of the lysine-modified curcumin prepared in step S3 in 50 mL of anhydrous DCM and add it to the reaction system at a rate of 1 mL / min while stirring at a rate of 200 rpm. After mixing evenly, add 3.5 mL of DIPEA to the reaction system at a rate of 1 drop / s and continue stirring. The polymerization reaction is carried out at room temperature for 48 h. After the reaction is completed, anhydrous diethyl ether at 4 °C is slowly added to the reaction system. After the precipitate precipitates, filter it, collect the precipitate, wash it with anhydrous diethyl ether, dissolve it in deionized water, transfer it to a pretreated dialysis bag (3000 Da), dialyze it in 500 mL of deionized water for 24 h, and freeze dry it to obtain polylysine-modified curcumin.

[0064] S5. Place 1.6 g of the polylysine-modified curcumin prepared in step S4 into a three-necked flask, and add 30 mL of ethanol aqueous solution (V 乙醇 :V 水 =3:2), after fully dispersing by stirring at 200 rpm, dissolve 80 mg of zinc acetate dihydrate and 90 mg of zinc nitrate hexahydrate in 20 mL of ethanol aqueous solution (V 乙醇 :V 水In a 3:2 ratio, ZnO was added dropwise to the reaction system at a rate of 1 mL / min, and stirred at 400 rpm. The complexation reaction was carried out at room temperature for 3 h. After the reaction was completed, 1 mol / L ammonia solution was added dropwise to the reaction system to adjust the pH to 7.8. After mixing evenly, the temperature of the reactants was raised to 55℃ to carry out the mineralization reaction for 7 h. After the reaction was completed, the reaction system was cooled to room temperature, and the reaction solution was transferred to a dialysis bag (5000 Da). Dialysis was performed with deionized water for 24 h. After dialysis, the solution was transferred to a centrifuge tube, centrifuged at 8000 rpm for 10 min, and the precipitate was collected. The precipitate was washed three times with anhydrous ethanol and freeze-dried to obtain ZnO@polylysine modified curcumin.

[0065] This embodiment also provides a method for preparing a composite gel material for gingival hemostasis, specifically including the following steps:

[0066] ① Take 1.0 g of ZnO@polylysine modified curcumin and 0.23 g of β-cyclodextrin and place them in 20 mL of deionized water. Sonicate at 300 W for 20 min to obtain the first dispersion.

[0067] ② Take 1.2g of sodium alginate and 0.8g of gelatin and place them in 20mL of deionized water. After the reactants are fully dissolved by raising the temperature to 40℃, add the first dispersion prepared in step ① dropwise to the reaction system and stir at 600rpm. After being fully dispersed, a suspension is obtained.

[0068] ③ Take the suspension prepared in step ②, add 0.4g of ammonium bicarbonate to it, stir at 450rpm for 10min, transfer to a mold, and place at a constant temperature of 37℃ for pore formation reaction for 30min. After the reaction, add 20mL of calcium chloride solution for cross-linking reaction. After 15min, take out the gel, wash it 3 times with deionized water, then wash it 2 times with anhydrous ethanol, squeeze the sponge to remove excess liquid, and pre-freeze it in a -50℃ ultra-low temperature freezer for 4h. Transfer it to a freeze dryer, set the vacuum degree ≤10Pa, and freeze-dry for 24h. After freeze-drying, take it out, demold it, and cut it according to the wound size. Place it in a sterile packaging bag and sterilize it with γ-rays to obtain the composite gel material. After sterilization, seal and store it.

[0069] Example 3

[0070] This embodiment provides a composite gel material for gingival hemostasis, the composite gel material comprising the following components in parts by weight: 1.2 parts ZnO@polylysine modified curcumin, 1.5 parts sodium alginate, 1.0 part gelatin, 0.5 parts ammonium bicarbonate, and 0.3 parts β-cyclodextrin;

[0071] The preparation method of ZnO@polylysine modified curcumin specifically includes the following steps:

[0072] S1. Accurately weigh 2.7 g of 4-bromo-3-methoxybenzaldehyde and place it in a flask. Add 50 mL of anhydrous ethanol and completely dissolve the 4-bromo-3-methoxybenzaldehyde. Then, dissolve 0.7 mL of acetylacetone in 5 mL of anhydrous ethanol and add it to the reaction system. After mixing evenly, add 0.092 mL of tributyl borate and 0.070 mL of piperidine to the reaction system. Stir at 200 rpm to form a homogeneous reaction system. Raise the reaction temperature to 85 °C and react for 6 h. After the reaction is complete, remove excess reaction solvent by rotary evaporation. After recrystallization purification, dry under vacuum at 40 °C for 6 h to obtain bromosubstituted curcumin.

[0073] S2. Place 0.4g of anhydrous potassium carbonate in a flask, add 50mL of anhydrous DMF to dissolve the potassium carbonate, add 2.5g of Boc-L-lysine to the flask, stir at 300rpm, raise the reaction temperature to 30℃, and stir the reactants until completely dissolved. Take 2.5g of the bromosubstituted curcumin prepared in step S1 and dissolve it in 10mL of anhydrous DMF. Add it to the reaction system through a constant pressure dropping funnel at a rate of 1 drop / s. Continue stirring and mixing until uniform. Raise the reaction temperature to 80℃ to carry out the substitution reaction. After the reaction is completed, after the reaction system is cooled to room temperature, add ice water to quench the reaction. Add ethyl acetate for multiple extractions, collect the organic phase, wash with saturated sodium chloride solution, remove water and dry the washed organic phase with anhydrous sodium sulfate, concentrate under reduced pressure to remove organic solvent, purify and dry to obtain Boc-lysine modified curcumin.

[0074] S3. Take the Boc-lysine modified curcumin prepared in step S2 and place it in a flask. Add 80 mL of anhydrous DCM to completely dissolve it. Transfer the reaction system to an ice-water bath for sufficient cooling. Dissolve 7.5 mL of trifluoroacetic acid in 20 mL of anhydrous DCM and slowly add it dropwise to the reaction system at a rate of 1 mL / min. At the same time, stir the reaction at a rate of 400 rpm. After the dropwise addition is complete, remove the ice-water bath and carry out the deprotection reaction at room temperature. After 1.5 h, add triethylamine dropwise to adjust the pH of the reaction to 7.5. Add anhydrous diethyl ether and stir the reaction. Remove excess solvent and reactants by vacuum distillation. After adding anhydrous diethyl ether to precipitate the precipitate, filter it, collect the filtrate, concentrate it under vacuum, and obtain lysine modified curcumin.

[0075] S4. Accurately weigh 2.2g of EDC·HCl and 1.55g of HOBt and dissolve them in 50mL of anhydrous DCM. After completely replacing the air in the reaction system with flowing nitrogen, dissolve 1.9g of the lysine-modified curcumin prepared in step S3 in 50mL of anhydrous DCM and add it to the reaction system at a rate of 1mL / min while stirring at 250rpm. After mixing evenly, add 4mL of DIPEA to the reaction system at a rate of 1 drop / s and continue stirring. The polymerization reaction is carried out at room temperature for 42h. After the reaction is completed, anhydrous diethyl ether at 4℃ is slowly added to the reaction system. After the precipitate precipitates, filter it, collect the precipitate, wash it with anhydrous diethyl ether, dissolve it in deionized water, transfer it to a pretreated dialysis bag (3000Da), dialyze it in 500mL of deionized water for 24h, and freeze-dry it to obtain polylysine-modified curcumin.

[0076] S5. Place 1.7 g of the polylysine-modified curcumin prepared in step S4 into a three-necked flask, and add 30 mL of ethanol aqueous solution (V 乙醇 :V 水 =3:2), after fully dispersing by stirring at 200 rpm, dissolve 65 mg of zinc acetate dihydrate and 120 mg of zinc nitrate hexahydrate in 20 mL of ethanol aqueous solution (V 乙醇 :V 水 In a 3:2 ratio, ZnO was added dropwise to the reaction system at a rate of 1 mL / min, and stirred at 500 rpm. The complexation reaction was carried out at room temperature for 2 h. After the reaction was completed, 1 mol / L ammonia solution was added dropwise to the reaction system to adjust the pH of the reaction system to 8.0. After mixing evenly, the temperature of the reactants was raised to 60℃ to carry out the mineralization reaction for 6 h. After the reaction was completed, the reaction system was cooled to room temperature, and the reaction solution was transferred to a dialysis bag (5000 Da). Dialysis was performed with deionized water for 24 h. After dialysis, the solution was transferred to a centrifuge tube, centrifuged at 8000 rpm for 10 min, and the precipitate was collected. The precipitate was washed three times with anhydrous ethanol and freeze-dried to obtain ZnO@polylysine modified curcumin.

[0077] This embodiment also provides a method for preparing a composite gel material for gingival hemostasis, specifically including the following steps:

[0078] ① Take 1.2g of ZnO@polylysine modified curcumin and 0.3g of β-cyclodextrin and place them in 20mL of deionized water. Sonicate at 400W for 15min to obtain the first dispersion.

[0079] ② Take 1.5g of sodium alginate and 1.0g of gelatin and place them in 20mL of deionized water. After the reactants are fully dissolved by raising the temperature to 40℃, add the first dispersion prepared in step ① dropwise to the reaction system and stir at 550rpm. After being fully dispersed, a suspension is obtained.

[0080] ③ Take the suspension prepared in step ②, add 0.5g of ammonium bicarbonate to it, stir at 500rpm for 10min, transfer to a mold, and place at a constant temperature of 37℃ for pore formation reaction for 30min. After the reaction, add 20mL of 1wt% calcium chloride solution for cross-linking reaction. After 15min, take out the gel, wash it 3 times with deionized water, then wash it 2 times with anhydrous ethanol, squeeze the sponge to remove excess liquid, and pre-freeze it in a -50℃ ultra-low temperature freezer for 4h. Transfer it to a freeze dryer, set the vacuum degree to ≤10Pa, and freeze-dry for 24h. After freeze-drying, take it out, demold it, and cut it according to the wound size. Place it in a sterile packaging bag and sterilize it with γ-rays to obtain the composite gel material. After sterilization, seal and store it.

[0081] Comparative Example 1

[0082] This comparative example provides a composite gel material and its preparation method. The only difference between this example and Example 1 is that ZnO@polylysine-modified curcumin is replaced with the same weight parts of polylysine. The other components and their contents are the same as in Example 1.

[0083] Comparative Example 2

[0084] This comparative example provides a composite gel material and its preparation method. The only difference between this material and Example 1 is that ZnO@polylysine-modified curcumin is replaced with the same weight parts of polylysine-modified curcumin. The preparation method of polylysine-modified curcumin is the same as that of ZnO@polylysine-modified curcumin except that step S5 is not included. The remaining components and component contents are the same as those in Example 1.

[0085] Comparative Example 3

[0086] This comparative example provides a composite gel material and its preparation method. The only difference between this material and Example 1 is that ZnO@polylysine is used instead of ZnO@polylysine-modified curcumin in the same weight proportions. The preparation method of ZnO@polylysine is the same as that of ZnO@polylysine-modified curcumin except that steps S1, S2 and S3 are not included. The remaining components and component contents are the same as in Example 1.

[0087] Experimental Example 1

[0088] This experiment tested the swelling properties of the composite gel materials prepared in Examples 1-3 and Comparative Examples 1-3. The swelling rate was calculated by measuring the amount of liquid absorbed by the sponge in simulated saliva (pH=7.2, composition: NaCl 0.9g / L, KCl 0.14g / L, NaHCO3 0.2g / L) at different times, reflecting its ability to rapidly absorb blood and concentrate coagulation components. Three parallel samples were taken for each sample, vacuum dried at 40℃ to constant weight, and the dry weight (W0, unit: g) was accurately measured. The samples were then immersed in simulated saliva preheated at 37℃, and removed at 1 min, 3 min, 5 min, 10 min, and 30 min respectively. The surface free liquid was gently blotted dry with filter paper, and the wet weight (W0, unit: g) was accurately measured. t (Unit: g) When the change in swelling rate between two consecutive time points is ≤5%, it is considered to have reached equilibrium. Record the equilibrium swelling time and calculate the swelling rate (SR, %) according to the following formula:

[0089] ;

[0090] Figure 1 The figure shows the swelling rate results of the composite gel materials prepared in Examples 1-3 and Comparative Examples 1-3 of this invention. As shown in the figure, the swelling rate of Examples 1-3 reached more than 2000% in 3-5 minutes, which means that the liquid absorption ratio reached more than 20 times. In the examples, polylysine provides a hydrophilic segment, which enables the composite gel material to absorb liquid quickly, while curcumin segments provide a hydrophobic segment. Combined with the coordination effect of ZnO, the excessive swelling of the composite gel material is limited, so that the pores remain connected after swelling. This satisfies the need for rapid liquid absorption in large-area bleeding and maintains structural stability. In Comparative Example 1, only the hydrophilic segment of polylysine was present, lacking hydrophobic rigid support. After swelling, the pores collapsed, and the swelling rate reached more than 1800% in 3 minutes, with no significant increase in the later stage. In Comparative Example 2, there was a hydrophobic chain of curcumin but no ZnO coordination to enhance rigidity. After swelling, some pores collapsed, and the swelling rate reached more than 1500% in 3 minutes. In Comparative Example 3, only polylysine and ZnO were present, lacking the hydrophobic network of curcumin. The structure was loose, and the swelling rate reached more than 1600% in 3 minutes.

[0091] Experiment Example 2

[0092] This experiment demonstrates in vitro coagulation experiments on the composite gel materials prepared in Examples 1-3 and Comparative Examples 1-3. Three parallel samples of each type were cut to 1cm × 1cm × 0.5cm and placed in a 24-well plate. The plate was preheated at 37℃ for 30 min. 0.2 mL of fresh rabbit blood (anticoagulant: sodium citrate, volume ratio 1:9) was added to each well, along with 0.02 mL of 0.025 mol / L CaCl2 (to activate the coagulation pathway). At 1 min, 3 min, and 5 min, 5 mL of deionized water was added to each well, and the plate was gently shaken for 10 s. The absorbance (A) was measured at 540 nm using a microplate reader. The absorbance of the blank control group (no sample) was (A0). The clot formation rate (%) was calculated using the following formula:

[0093] ;

[0094] Another set of samples was taken and PT (prothrombin time) and APTT (activated partial thromboplastin time) were measured using a coagulation analyzer.

[0095] Figure 2 The graphs show the coagulation performance results of the composite gel materials prepared in Examples 1-3 and Comparative Examples 1-3 of this invention. Figure 3 The figures show the coagulation time results of the composite gel materials prepared in Examples 1-3 and Comparative Examples 1-3 of this invention. In the examples, coagulation can be rapidly initiated within 1 minute, and a blood clot formation rate of over 90% can be achieved within 3 minutes. In Comparative Example 1, the formation rate within 1 minute is only 20.21%, and the PT / APTT is far higher than that of normal rabbit blood. Rapid coagulation cannot be achieved solely through the cationic adsorption of polylysine. The lack of curcumin activation of coagulation factors results in poor blood clot stability. The lack of ZnO concentration of coagulation factors results in slow coagulation initiation. In Comparative Example 2, the formation rate within 1 minute is 50.51%, and the coagulation initiation speed is slow due to the lack of ZnO concentration. However, curcumin can still enhance blood clot stability. In Comparative Example 3, the formation rate within 1 minute is 55.57%, because the physical adsorption of ZnO can accelerate the coagulation initiation, but the lack of curcumin activation of coagulation factors results in weak blood clot stability.

[0096] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention.

[0097] The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention. The actual application is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar methods and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.

Claims

1. A composite gel material for gingival hemostasis, characterized by: The composite gel material comprises the following components by weight: ZnO@ polylysine modified curcumin 0.8-1.2 parts, sodium alginate 1.0-1.5 parts, gelatin 0.6-1.0 parts, ammonium bicarbonate 0.3-0.5 parts, and beta-cyclodextrin 0.15-0.3 parts. The preparation method of the ZnO@ polylysine modified curcumin specifically comprises the following steps: S1, 4-bromo-3-methoxybenzaldehyde is dissolved in anhydrous ethanol, acetylacetone is added, the reaction system is mixed uniformly, then tributyl borate and piperidine are added, the reaction temperature is increased for reflux reaction, after the reaction is completed, the reaction system is cooled, the excess organic solvent is removed by rotary evaporation, and then the product is purified and dried to obtain bromine-substituted curcumin; S2, anhydrous potassium carbonate is dissolved in anhydrous DMF, Boc-L-lysine is added, and the reaction system is stirred until the reactants are completely dissolved, then the bromine-substituted curcumin prepared in step S1 is dissolved in anhydrous DMF, and the reaction system is added dropwise through a constant-pressure dropping funnel, mixed uniformly, and then the reaction temperature is increased for substitution reaction, after the reaction is completed, the reaction system is cooled, ice water is added for quenching reaction, ethyl acetate is added for multiple extractions, the organic phase is collected, washed with saturated sodium chloride solution, and then the washed organic phase is dried over anhydrous sodium sulfate, the organic solvent is removed by reduced pressure concentration, and then the product is purified and dried to obtain Boc-lysine modified curcumin; S3, the Boc-lysine modified curcumin prepared in step S2 is dissolved in anhydrous dichloromethane, transferred to an ice water bath for cooling, trifluoroacetic acid is slowly added dropwise to the reaction system, after the addition is completed, the reaction system is neutralized by adding triethylamine, the excess solvent and reactants are removed by reduced pressure distillation, anhydrous diethyl ether is added to precipitate a precipitate, the precipitate is filtered, the filtrate is collected, and then the product is obtained by reduced pressure concentration to obtain lysine modified curcumin; S4, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and 1-hydroxybenzotriazole are dissolved in anhydrous dichloromethane, nitrogen gas is introduced, the lysine modified curcumin prepared in step S3 is dissolved in anhydrous dichloromethane, and then the reaction system is added dropwise, mixed uniformly, slowly added with N,N-diisopropyl ethylamine to the reaction system, and then the reaction is carried out at room temperature, after the reaction is completed, 4℃ anhydrous diethyl ether is slowly added to the reaction system, a precipitate is precipitated, the precipitate is filtered, washed with anhydrous diethyl ether, dissolved in deionized water, purified by dialysis, and then freeze-dried to obtain polylysine modified curcumin; S5, the polylysine modified curcumin prepared in step S4 is dissolved in an ethanol aqueous solution, zinc acetate dihydrate and zinc nitrate hexahydrate are dissolved in the ethanol aqueous solution, slowly added dropwise to the reaction system, and then the reaction is carried out at room temperature, after the reaction is completed, ammonia water solution is added dropwise to the reaction system, the pH of the reaction is adjusted to 7.5-8.0, mixed uniformly, and then the reaction is carried out at an increased temperature, after the reaction is completed, the reaction system is cooled, dialyzed in deionized water, and then freeze-dried to obtain ZnO@ polylysine modified curcumin.

2. The composite gel material for hemostasis of gingiva according to claim 1, wherein: In step S1, the mass-volume ratio between the 4-bromo-3-methoxybenzaldehyde and acetylacetone is 2.2-2.7 g:0.5-0.7 mL; the volume ratio between the tributyl borate and acetylacetone is 0.13-0.18:1; the volume ratio between the piperidine and acetylacetone is 1-1.2:

1.

3. The composite gel material for hemostasis of gingiva according to claim 2, wherein: In step S1, the reaction temperature of the reflux reaction is 75-85℃, and the reaction time of the reflux reaction is 6-8h.

4. The composite gel material for hemostasis of gingiva according to claim 3, wherein: In step S2, the mass ratio between the Boc-L-lysine and anhydrous potassium carbonate is 2.0-2.5:0.3-0.4; the mass ratio between the bromine-substituted curcumin and Boc-L-lysine is 1.9-2.5:2.0-2.5; the reaction temperature of the substitution reaction is 70-80℃, and the reaction time of the substitution reaction is 12-16h.

5. The composite gel material for hemostasis of gingiva according to claim 4, wherein: In step S3, the mass-volume ratio between the Boc-L-lysine and trifluoroacetic acid in step S2 is 2.0-2.5 g:6-7.5 mL; the stirring speed of the deprotection reaction is 200-400 rpm, and the time of the deprotection reaction is 1.5-2.5h.

6. The composite gel material for hemostasis of gingiva according to claim 5, wherein: In step S4, the mass ratio between the lysine-modified curcumin, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and 1-hydroxybenzotriazole is 1.6-1.9:1.8-2.2:1.55-1.65; the mass-volume ratio between the lysine-modified curcumin and N,N-diisopropylethylamine is 0.47-0.53 g / mL; the stirring speed of the polymerization reaction is 300-400 rpm, and the reaction time of the polymerization reaction is 36-48h.

7. The composite gel material for hemostasis of gingiva according to claim 6, wherein: In step S5, the mass ratio between the zinc acetate dihydrate and zinc nitrate hexahydrate is 0.055-0.08:0.075-0.12; the mass ratio between the polylysine-modified curcumin and the total amount of zinc acetate dihydrate and zinc nitrate hexahydrate is 1.4-1.7:0.13-0.

185.

8. The composite gel material for hemostasis of gingiva according to claim 7, wherein: In step S5, the stirring speed of the complexation reaction is 300-500 rpm, and the time of the complexation reaction is 2-4h; the reaction temperature of the mineralization reaction is 50-60℃, and the reaction time of the mineralization reaction is 6-8h.

9. A process for the preparation of a composite gel material for hemostasis of gingiva according to any one of claims 1 to 8, characterized by: Specifically comprising the following steps: ①, take ZnO@polylysine-modified curcumin and β-cyclodextrin in deionized water, and perform ultrasonic treatment under 250-400 W power, and after 15-30 min, a first dispersion liquid is obtained; ②, take sodium alginate and gelatin in deionized water, and after the reactants are fully dissolved by increasing the temperature, the first dispersion liquid prepared in step ① is added dropwise into the reaction system, and stirring is performed at a speed of 500-600 rpm, and after being fully dispersed, a suspension liquid is obtained; ③, take the suspension liquid prepared in step ②, and add ammonium bicarbonate thereto, and after stirring at 400-500 rpm for 10-15 min, it is transferred into a mold, and is subjected to a pore-forming reaction under constant temperature conditions, and after the reaction is completed, a calcium chloride solution is added, and a crosslinking reaction is performed, and after washing, freeze-drying, demolding and cutting, sterilization is performed, and a composite gel material is obtained.

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