High-adhesion hemostatic peach gum hydrogel, preparation method and application thereof in wound hemostatic material

Abstract

This invention belongs to the field of biomedical materials and biomedical engineering technology, and discloses a highly adhesive hemostatic gum hydrogel, its preparation method, and its application in wound hemostasis materials. The preparation method involves mixing natural gum with citric acid and heating the mixture until it forms a gel, thus preparing a natural, safe, biocompatible, and highly adhesive gum hydrogel. This highly adhesive hemostatic gum hydrogel exhibits excellent biocompatibility, tissue adhesion, and rapid hemostasis, and can be applied to wound hemostasis in tissues such as the uterus and skin.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials and biomedical engineering technology, and relates to a highly adhesive hemostatic gum hydrogel, its preparation method, and its application in wound hemostatic materials. Background Technology

[0002] Whether it's myomectomy, adenomyosis lesion removal, cervical conization, or endometrial resection, the procedure often results in a large area of ​​diffuse bleeding wounds or deep sutures that are difficult to completely close. These wounds are irregular in shape, rich in blood supply, and are in a moist environment constantly flushed by uterine secretions.

[0003] Currently, common hemostasis methods in gynecological surgery include electrocoagulation, suturing and ligation, and packing with traditional hemostatic materials. However, existing methods have significant limitations: electrocoagulation has limited effectiveness in deep or diffuse wounds and is prone to thermal damage, affecting surrounding normal tissues; traditional materials such as gelatin sponges and oxidized cellulose can be placed into the wound cavity, but they have poor adhesion to gynecological wounds rich in tissue fluid and blood, easily shifting or falling off, and their degradation rate is difficult to match with the tissue repair cycle; some synthetic materials, although possessing certain hemostatic activity, have poor biocompatibility and may induce inflammatory reactions, tissue adhesions, or affect post-healing tissue elasticity in the special physiological environment of reproductive organs such as the uterus and ovaries, posing a potential risk to the fertility reserves of patients of childbearing age.

[0004] Hydrogel hemostatic materials, with their three-dimensional hydrophilic network, tunable mechanical properties, and excellent tissue adhesion, offer a new solution for hemostasis in gynecological wounds. An ideal hydrogel material should not only rapidly absorb concentrated clotting factors from the wound but also possess excellent wet adhesion properties. Its viscoelasticity allows it to tightly adhere to irregular cavities, resisting blood flushing and achieving physical sealing of deep or diffuse bleeding. Simultaneously, by introducing active groups or loading hemostatic factors, it can actively participate in the coagulation cascade reaction, achieving rapid and stable hemostasis. However, hydrogel research for gynecological surgical scenarios still faces many challenges: how to achieve synergistic optimization of multiple properties—rapid hemostasis (to cope with abundant blood supply), strong wet adhesion (to resist uterine secretion flushing), controllable degradation (to match the wound healing cycle), and anti-adhesion (to protect fertility)—while ensuring the biosafety of reproductive organs, is the core bottleneck restricting its clinical translation.

[0005] Therefore, developing a hydrogel material that combines high hemostatic properties, excellent biocompatibility, gynecological tissue compatibility, and ease of clinical operation is of great clinical significance and scientific value for reducing the risk of bleeding during gynecological surgery and reducing postoperative complications. Summary of the Invention

[0006] The purpose of this invention is to provide a highly adhesive hemostatic gum hydrogel. This hydrogel is a pure natural hydrogel with wet adhesion and hemostatic properties. It can be applied to the treatment of bleeding from uterine wounds, and its preparation process is simple.

[0007] In a first aspect, the present invention provides a method for preparing a highly adhesive hemostatic gum hydrogel, characterized in that the preparation method comprises the following steps:

[0008] S1. Mix natural peach gum, citric acid and water evenly to obtain a citric acid / peach gum mixed solution;

[0009] S2. Heating the citric acid / gum mixture solution to induce a cross-linking reaction until gelation occurs, yielding a highly adhesive hemostatic gum hydrogel.

[0010] Furthermore, in step S1, the mass ratio of peach gum to citric acid is (1-2):0.45.

[0011] Furthermore, in step S1, the mass ratio of peach gum to water is (1-2):0.67.

[0012] Furthermore, in step S2, the heating specifically refers to heating to 90℃-93℃.

[0013] Furthermore, in step S2, the crosslinking reaction takes 3 hours.

[0014] In a second aspect, the present invention provides a highly adhesive hemostatic gum hydrogel prepared according to the above-described preparation method.

[0015] In a fourth aspect, the present invention provides the application of the above-mentioned highly adhesive hemostatic gum hydrogel in wound hemostatic materials.

[0016] In a fifth aspect, the present invention provides the application of the above-mentioned highly adhesive hemostatic gum hydrogel in hemostatic materials for gynecological surgical wounds.

[0017] Compared with the prior art, the present invention has the following technical effects:

[0018] (1) The present invention uses all-natural raw materials, with peach gum as the natural polysaccharide matrix and food-grade citric acid as the crosslinking agent. It can be prepared by a one-pot process of simple mixing and high-temperature heating without complicated operation or introduction of toxic reagents. The citric acid crosslinked peach gum hydrogel has extremely high biosafety and biocompatibility, which can avoid inflammatory stimulation and toxic side effects, and provides a safe and reliable material choice for clinical hemostasis.

[0019] (2) The citric acid crosslinked gum hydrogel prepared by the present invention exhibits excellent adhesion and hemostatic efficacy under the premise of extremely simple preparation process and natural and safe raw materials: the three-dimensional polysaccharide network constructed by thermal crosslinking of citric acid can adhere tightly to the moist wound surface, quickly seal the damaged area and promote coagulation, while maintaining good water and air permeability. It not only solves the problems of insufficient adhesion and complicated preparation of traditional hemostatic materials, but also breaks through the bottleneck of low biosafety of chemically synthesized hemostatic materials, and has significant clinical application potential in the field of wound hemostasis. Attached Figure Description

[0020] To more clearly illustrate the technical solutions of the present invention, the accompanying drawings used in the description of the embodiments or prior art will be briefly introduced below. Obviously, the drawings described below are merely some embodiments of the present invention, and those skilled in the art can obtain other drawings based on these drawings without any creative effort.

[0021] Figure 1 These are adhesion strength test diagrams for samples from Examples 1, 2, and 3, providing a direct comparison of the differences in tissue adhesion properties of hydrogels obtained from different concentrations of peach gum.

[0022] Figure 2 This is a test chart of the adhesion strength between the sample of Example 3 and 502 glue, which visually compares the differences in the tissue adhesion properties of the two materials;

[0023] Figure 3 The images show the hemostatic effect of the liver in Example 3, with the blank group showing liver wounds without the hydrogel and the Example 3 sample group showing liver wounds using the hydrogel, demonstrating that the Example 3 sample has excellent hemostatic properties. Detailed Implementation

[0024] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0025] Example 1

[0026] Mix 0.55g of natural peach gum, 0.45g of citric acid and 0.67g of water until homogeneous, heat in a water bath at 90°C for 3 hours to obtain peach gum hydrogel based on citric acid crosslinking (sample of Example 1).

[0027] Example 2

[0028] 1.00g of natural peach gum, 0.45g of citric acid and 0.67g of water were mixed and stirred evenly. The mixture was heated in a water bath at 90°C for 3 hours to obtain peach gum hydrogel based on citric acid crosslinking (sample of Example 2).

[0029] Example 3

[0030] 1) Mix 2.00g of natural peach gum, 0.45g of citric acid and 0.67g of water evenly, heat in a water bath at 93°C for 3 hours to obtain peach gum hydrogel based on citric acid crosslinking (sample of Example 3).

[0031] Comparative Example 1

[0032] 0.55g of natural peach gum, 0.45g of citric acid and 0.67g of water were mixed and stirred evenly. The mixture was heated in a water bath at 80℃ for 3 hours, but no peach gum hydrogel based on citric acid crosslinking was obtained.

[0033] 0.55g of natural peach gum, 0.45g of citric acid and 0.67g of water were mixed and stirred evenly. The mixture was heated in a water bath at 100℃ for 3 hours, but no peach gum hydrogel based on citric acid crosslinking was obtained.

[0034] Comparative Example 2

[0035] 0.1g of natural peach gum, 0.45g of citric acid and 0.67g of water were mixed and stirred evenly. The mixture was heated in a water bath at 90℃ for 3 hours, but no peach gum hydrogel based on citric acid crosslinking was obtained.

[0036] 3g of natural peach gum, 0.45g of citric acid and 0.67g of water were mixed and stirred evenly. The mixture was heated in a water bath at 90℃ for 3 hours, but no peach gum hydrogel based on citric acid crosslinking was obtained.

[0037] The adhesion of samples from Examples 1, 2, and 3 was tested using the pigskin shear-overlap method: Pigskin was cut into 1 cm × 2 cm specimens, and the hydrogel was adhered between two pieces of pigskin. A universal testing machine was used to perform a shear-tensile test at a constant rate. The maximum load at material fracture was recorded, and the adhesion strength was calculated. The results are as follows: Figure 1 As shown, the left figure is the shear force-time S-curve for different samples, and the right figure is a bar chart of the adhesion force of the three groups of samples. Figure 1 It can be seen that the adhesion of the sample in Example 3 is significantly higher than that of the samples in Examples 1 and 2.

[0038] We then selected the sample from Example 3, which exhibited the best adhesion, and compared its adhesion performance with that of 502 glue. The results are as follows: Figure 2 As shown. According to Figure 2As can be seen, compared with 502 glue, the hydrogel in Example 3, while ensuring considerable adhesion strength, has better biocompatibility and clinical applicability, and can meet the needs of wound hemostasis and wound closure.

[0039] To verify the actual efficacy of the sample in Example 3 for in vivo wound hemostasis, 8-week-old female SD rats were selected as experimental animals. After anesthesia, the abdominal cavity was opened to expose the liver, and pre-weighed quantitative filter paper was placed under the liver. A liver puncture model was established using a 5 mL syringe needle with an insertion depth of 2–3 mm. In the control group, hemostasis was achieved naturally after applying light pressure with cotton for 3 seconds. In the experimental group, citric acid-crosslinked gum arabic hydrogel was applied to the wound after applying light pressure for 3 seconds. After the bleeding completely stopped, the weight of the filter paper was weighed again to calculate the blood loss, and the bleeding time of each group was recorded simultaneously. The results are as follows: Figure 3 As shown, the top figure is a time series comparison of the bleeding process of the liver wound in two groups of rats; the bottom left figure is a bar chart of the bleeding volume in the two groups of rats; and the bottom right figure is a bar chart of the bleeding time in the two groups of rats. According to... Figure 3 It can be seen that the amount of bleeding and the bleeding time in the sample group of Example 3 were significantly lower than those in the blank control group, demonstrating excellent rapid hemostasis effect.

[0040] The foregoing description has fully disclosed the specific embodiments of the present invention. It should be noted that any modifications made to the specific embodiments of the present invention by those skilled in the art do not depart from the scope of the claims. Accordingly, the scope of the claims is not limited to the foregoing specific embodiments.

Claims

1. A method for preparing a highly adhesive hemostatic gum hydrogel, characterized in that, The preparation method includes the following steps: S1. Mix natural peach gum, citric acid and water evenly to obtain a citric acid / peach gum mixed solution; S2. Heating the citric acid / gum mixture solution to induce a cross-linking reaction until gelation occurs, yielding a highly adhesive hemostatic gum hydrogel.

2. The preparation method according to claim 1, characterized in that, In step S1, the mass ratio of peach gum to citric acid is (1-2):0.

45.

3. The preparation method according to claim 1, characterized in that, In step S1, the mass ratio of peach gum to water is (1-2):0.

67.

4. The preparation method according to claim 1, characterized in that, In step S2, the heating specifically refers to heating to 90℃-93℃.

5. The preparation method according to claim 1, characterized in that, In step S2, the crosslinking reaction takes 3 hours.

6. A highly adhesive hemostatic gum hydrogel prepared by the preparation method according to any one of claims 1-5.

7. The application of the highly adhesive hemostatic gum hydrogel as described in claim 6 in wound hemostatic materials.

8. The application of the highly adhesive hemostatic gum hydrogel as described in claim 6 in hemostatic materials for gynecological surgical wounds.

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