Composition of hydrogel adhesive as well as preparation method and application of composition

Abstract

The invention provides a hydrogel adhesive composition as well as a preparation method and application thereof, and belongs to the field of biomedical engineering. The hydrogel adhesive composition is prepared from the following raw materials: natural polysaccharide macromolecules, monomer micromolecules, an initiator, a cross-linking agent and an ionic salt solution. The preparation method comprises the following steps: (1) dissolving natural polysaccharide macromolecules and monomer micromolecules in water, adding an initiator and a cross-linking agent, and stirring and dissolving to obtain a hydrogel precursor solution A; (2) initiating free radical polymerization of the hydrogel precursor solution A to form a hydrogel intermediate B; and (3) soaking the hydrogel intermediate B in the ionic salt solution again to obtain the composition of the hydrogel adhesive. The method is simple in process and mild in reaction condition, and the obtained hydrogel has good adhesion performance and biocompatibility.

Description

Technical Field

[0001] The present invention relates to the fields of biomedicine technology and wound hemostasis, and in particular to a hydrogel adhesive composition, a preparation method and an application thereof. Background Art

[0002] Open wound bleeding is a very common type of injury caused by traffic accidents, natural disasters, extreme sports and surgical operations. Excessive blood loss in a short period of time can lead to shock, infection and even loss of life. Therefore, the development of multifunctional biohemostatic materials for wound bleeding is urgent and has great significance for damage control at the emergency scene.

[0003] High adhesion is the key to the performance of hemostatic materials. Currently, the widely used cyanoacrylate adhesive resin has strong adhesion, but it will quickly harden to form a hard plastic layer at the wet tissue interface, lose its adhesion performance, and its biocompatibility is poor. Hydrogel-based hemostatic materials have tissue similarity and biocompatibility and are advantageous hemostatic materials. However, the presence of a large amount of water in the hydrogel makes it very difficult to achieve strong adhesion with most matrices, especially wet tissues. Traditional hydrogel adhesion enhancement strategies, such as surface modification based on catechol, topological entanglement and dynamic covalent crosslinking (such as Schiff base formation), can improve the adhesion performance of hydrogels to a certain extent. However, these strategies mainly focus on interfacial bonding, and ignore the adjustment of hydrogel cohesion, which has limited effect on the improvement of hydrogel adhesion. In addition, these methods are usually faced with the problems of complex synthesis process, long time consumption and poor scalability. Summary of the Invention

[0004] In view of the problems existing in the prior art, the present invention aims to provide a hydrogel adhesive composition, a preparation method, and an application thereof, so that the hydrogel adhesive has good tissue adhesion. Furthermore, another object of the present invention is to provide a method for preparing the hydrogel adhesive composition, so that the preparation method of the hydrogel adhesive is simple and efficient.

[0005] In order to achieve the purpose of this invention, the present invention adopts the following technical solutions:

[0006] The invention provides a hydrogel adhesive composition. The raw materials for preparing the hydrogel adhesive composition include natural polysaccharide macromolecules, monomer small molecules, an initiator, a crosslinking agent and an ion salt solution.

[0007] Preferably, the natural polysaccharide polymer in the composition is any one of carboxymethyl chitosan, sodium alginate, chitosan, cellulose, starch or agar.

[0008] Preferably, the monomer small molecule in the composition is any one of acrylic acid or acrylamide.

[0009] Preferably, the initiator and the cross-linking agent in the composition are any one or a combination of two of ammonium persulfate, sodium persulfate, potassium persulfate, and N,N-methylenebisacrylamide.

[0010] Preferably, the ionic salt solution in the composition is any one of NaCl, KCl, MgCl2 and CaCl2.

[0011] Preferably, the ionic salt solution is a saturated solution.

[0012] The preparation method of the hydrogel adhesive composition of the present invention is to achieve the aggregation of hydrogel polymers induced by ion salting-out effect by a simple salt solution soaking method after heat-induced self-polymerization.

[0013] The present invention also provides a method for preparing a hydrogel adhesive composition, comprising the following steps:

[0014] (1) dissolving natural polysaccharide polymers and monomeric small molecules in water, adding an initiator and a cross-linking agent, and stirring to dissolve to obtain a hydrogel precursor solution A;

[0015] (2) initiating free radical polymerization of the hydrogel precursor solution A to form a hydrogel intermediate B;

[0016] (3) Soaking the hydrogel intermediate B again in an ionic salt solution to obtain the hydrogel adhesive composition.

[0017] In step (1), the amount of the natural polysaccharide polymer relative to 100 mL of water is 0.5 to 4 g, for example, 0.5 g, 0.8 g, 1 g, 1.5 g, 2 g, 2.5 g, 3 g, 3.5 g or 4 g.

[0018] Preferably, in step (1), the amount of the monomer small molecule relative to 100 mL of water is 1 to 40 g, for example, 1 g, 3 g, 5 g, 8 g, 10 g, 15 g, 18 g, 20 g, 23 g, 25 g, 28 g, 30 g, 35 g, 38 g or 40 g.

[0019] Preferably, in step (1), the amount of the initiator and the cross-linking agent used is independently 0.1 to 1 g, such as 0.1 g, 0.3 g, 0.5 g, 0.7 g, 0.9 g or 1 g, relative to 100 mL of water.

[0020] Preferably, the temperature of the free radical polymerization in step (2) is 40°C-100°C, for example 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C or 100°C.

[0021] Preferably, the time of the free radical polymerization in step (2) is 10-120 min, for example, 10 min, 20 min, 30 min, 40 min, 50 min, 60 min, 70 min, 80 min, 90 min, 100 min, 110 min or 120 min.

[0022] Preferably, the amount of the ionic salt in step (3) is 28-75 g relative to 100 mL of water in step (1);

[0023] In the present invention, step (3) involves immersing the intermediate in a salt solution to induce polymer aggregation by utilizing the ion salting-out effect, thereby ultimately preparing a hydrogel adhesive composition.

[0024] Preferably, the soaking time is 1 min-24 h, for example 1 min, 30 min, 1 h, 3 h, 5 h, 8 h, 10 h, 12 h, h, 15 h, 18 h, 20 h, 22 h or 24 h.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The hydrogel adhesive of the present invention has excellent adhesion properties and can easily achieve effective adhesion to iron, ceramics, PP plastics, skin and internal organs. The adhesion properties of the hydrogel adhesive of the present invention can be simply adjusted by immersion, and the preparation method is more suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Schematic diagram of the preparation process of the hydrogel adhesive composition in Example 1.

[0028] Figure 2 Schematic diagram of the scanning electron microscope of the hydrogel adhesive composition in Example 1.

[0029] Figure 3 This is a diagram showing the effect of the tail-chopping hemostasis model using the hydrogel adhesive composition in Example 1.

[0030] Figure 4 This is a diagram showing the effect of the cardiac hemostasis model of the hydrogel adhesive composition in Example 1. DETAILED DESCRIPTION

[0031] The technical solution of the present invention will be further described below with reference to the accompanying drawings and through specific embodiments. However, the following examples are merely simplified examples of the present invention and do not represent or limit the scope of protection of the present invention. The scope of protection of the present invention shall be subject to the claims.

[0032] Example 1

[0033] In the present invention, the hydrogel adhesive composition is prepared by the following method, and the preparation process is shown in the schematic diagram. Figure 1 As shown, the specific steps include:

[0034] (1) 0.4 g of carboxymethyl chitosan and 4 g of acrylamide were weighed and dissolved in 10 mL of deionized water. 0.04 g of ammonium persulfate and 0.01 g of N,N-methylenebisacrylamide were then added and stirred to dissolve to obtain a hydrogel precursor solution A.

[0035] (2) The hydrogel precursor solution A is placed in a certain mold, the temperature is adjusted to 65°C, and heated for 60 minutes to obtain a hydrogel intermediate B.

[0036] (3) The hydrogel intermediate B obtained in step (2) was added to a saturated solution of sodium chloride and soaked for 5 minutes to obtain a hydrogel adhesive C. Finally, the gel was freeze-dried and the microstructure was observed using a scanning electron microscope.

[0037] Example 2

[0038] In the present invention, the hydrogel adhesive composition is prepared by the following method, which specifically includes the following steps:

[0039] (1) Weigh 0.2 g of agar and 1 g of acrylic acid, respectively, and dissolve them in 10 mL of deionized water. Then, add 0.08 g of ammonium persulfate and 0.01 g of N,N-methylenebisacrylamide, and stir to dissolve to obtain a hydrogel precursor solution A.

[0040] (2) The hydrogel precursor solution A is placed in a certain mold, the temperature is adjusted to 85°C, and heated for 30 minutes to obtain a hydrogel intermediate B.

[0041] (3) The hydrogel intermediate B obtained in step (2) was added to a saturated solution of sodium chloride and soaked for 24 hours to finally obtain a hydrogel adhesive C.

[0042] Example 3

[0043] In the present invention, the hydrogel adhesive composition is prepared by the following method, which specifically includes the following steps:

[0044] (1) Weigh 0.1 g of sodium alginate and 2 g of acrylic acid, respectively, and dissolve them in 10 mL of deionized water. Then, add 0.1 g of ammonium persulfate and 0.04 g of N,N-methylenebisacrylamide, and stir to dissolve to obtain a hydrogel precursor solution A.

[0045] (2) The hydrogel precursor solution A is placed in a certain mold, the temperature is adjusted to 40°C, and heated for 120 minutes to obtain a hydrogel intermediate B.

[0046] (3) The hydrogel intermediate B obtained in step (2) was added to a saturated solution of sodium chloride and soaked for 24 hours to finally obtain a hydrogel adhesive C.

[0047] The hydrogel adhesive composition prepared in Example 1 was characterized by scanning electron microscopy (Hitachi High-Technologies Corporation, Japan, Hitachis-450). The results are as follows: Figure 1 As shown by Figure 1 It can be seen that the gel after being soaked in salt solution exhibits a finer porous structure.

[0048] The effects of the hydrogel adhesive composition in Example 1 on the tail hemostasis and cardiac hemostasis models were evaluated using the following methods:

[0049] To evaluate the efficacy of hemostatic materials in a tail-cut hemostasis model: Healthy adult mice (20-30 g) were anesthetized with isoflurane and immobilized, and the tails were disinfected. The tails were cut transversely (1-1.5 mm in diameter) 3-5 mm from the tip, and the initial bleeding time (T=0) was immediately recorded. Natural hemostasis was used in the control group, while the experimental group was treated with hemostatic materials and gently pressed for 10 seconds. The amount of bleeding (mg) was measured using the filter paper blood aspiration method, and observation was continued until complete hemostasis was achieved.

[0050] The efficacy of the hemostatic material in a mouse cardiac hemostasis model was evaluated: 25-30g C57BL / 6 mice were anesthetized with isoflurane and underwent thoracotomy to expose the left ventricle. A standard 0.3mm diameter wound was created using a 30G needle. The performance of the hemostatic material was systematically evaluated by recording hemostasis time and measuring bleeding volume (mg) using filter paper weighing.

[0051] The evaluation results of tail-cutting hemostasis effect are as follows Figure 3 As shown, compared with the natural hemostasis control group, the amount of blood adsorbed by the filter paper in the tail amputation model of mice in the gel treatment group was significantly reduced, indicating that the gel material can effectively control tail wound bleeding.

[0052] Further evaluation results of the cardiac hemostasis model were as follows Figure 4 As shown by Figure 4 It can be seen that the amount of blood absorbed by the gauze in the gel group was significantly less than that in the control group, confirming that the material also has a significant hemostatic effect on cardiac puncture wounds.

[0053] The present invention uses the above-described embodiments to illustrate the hydrogel adhesive composition, preparation method, and application thereof. However, the present invention is not limited to these embodiments, and implementation of the present invention is not necessarily dependent on these embodiments. Those skilled in the art will appreciate that any improvements to the present invention, equivalent replacements for selected components, additions of auxiliary components, and selection of specific methods are all within the scope of protection and disclosure of the present invention.

Claims

1. A hydrogel adhesive composition, characterized in that: The raw materials for preparing the hydrogel adhesive composition include natural polysaccharide macromolecules, monomer small molecules, initiators, crosslinking agents and ion salt solutions.

2. The hydrogel adhesive composition according to claim 1, characterized in that The natural polysaccharide polymer in the composition is any one of carboxymethyl chitosan, sodium alginate, chitosan, cellulose, starch or agar.

3. The hydrogel adhesive composition according to claim 1 or 2, characterized in that: The monomer small molecule in the composition is any one of acrylic acid or acrylamide; Preferably, the initiator and the cross-linking agent in the composition are any one or a combination of two of ammonium persulfate, sodium persulfate, potassium persulfate, and N,N-methylenebisacrylamide.

4. The hydrogel adhesive composition according to any one of claims 1 to 3, characterized in that: The ionic salt solution in the composition is any one of NaCl, KCl, MgCl2 or CaCl2; Preferably, the ionic salt solution is a saturated solution.

5. The method for preparing the hydrogel adhesive composition according to any one of claims 1 to 4, characterized in that: The preparation method comprises the following steps: (1) dissolving natural polysaccharide polymers and monomeric small molecules in water, adding an initiator and a cross-linking agent, and stirring to dissolve to obtain a hydrogel precursor solution A; (2) initiating free radical polymerization of the hydrogel precursor solution A to form a hydrogel intermediate B; (3) Soaking the hydrogel intermediate B again in an ionic salt solution to obtain the hydrogel adhesive composition.

6. The preparation method according to claim 5, characterized in that In step (1), the amount of the natural polysaccharide polymer is 0.5 to 4 g relative to 100 mL of water; Preferably, in step (1), the amount of the monomer small molecule is 1 to 40 g relative to 100 mL of water; Preferably, in step (1), the amount of the initiator and the cross-linking agent used is independently 0.1 to 1 g relative to 100 mL of water.

7. The preparation method according to claim 5, characterized in that The temperature of the free radical polymerization in step (2) is 40°C-100°C.

8. The preparation method according to claim 5, characterized in that The time of the free radical polymerization in step (2) is 10-120 minutes.

9. The preparation method according to claim 5, characterized in that The amount of ionic salt used in step (3) is 28-75 g relative to 100 mL of water in step (1); Preferably, the soaking time in step (3) is 1 min-24 h.

10. Use of the hydrogel adhesive composition according to any one of claims 1 to 4 in the preparation of hemostatic materials.

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