Peach gum-based self-repairing moisturizing hydrogel, preparation method and application of peach gum-based self-repairing moisturizing hydrogel in hemostasis and moisturizing materials
By borate-modifying peach gum and cross-linking it with sodium pyrrolidone carboxylate, a self-repairing moisturizing hydrogel was constructed, which solved the problems of insufficient efficiency and lack of self-repairing ability of existing hemostatic materials in large-area bleeding, and achieved the multifunctional effects of efficient hemostasis and self-repair.
Patent Information
- Application Number
- CN202511142361.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-15
- Publication Date
- 2025-09-19
AI Technical Summary
Existing hemostatic materials are not efficient enough in stopping bleeding when facing large-area bleeding, and lack self-repair capabilities. They are easily broken or fallen off under organ pulsation, increasing the complexity of surgery and postoperative effects.
By borate-modifying peach gum and then adding sodium pyrrolidone carboxylate to form borate ester cross-linking, a self-repairing moisturizing hydrogel is constructed. The hygroscopic function of sodium pyrrolidone carboxylate and the nucleophilic substitution reaction of the boric acid group are utilized to achieve self-repair and hemostasis multifunctionality.
It achieves efficient hemostasis and self-repair performance, enhances tissue adhesion, avoids the debonding problem of traditional adhesives, and improves hemostasis efficiency and self-repair ability.
Smart Images
Figure CN120661725A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of biomedical materials and biomedical engineering, and relates to a peach gum-based self-repairing moisturizing hydrogel, a preparation method and application of the hydrogel in hemostatic and moisturizing materials. Background Art
[0002] During clinical surgery, organs rich in blood vessels, such as the liver, present a significant risk of massive bleeding. This is especially true during surgical procedures, where cutting and moving organs can cause vascular ruptures, leading to emergency situations such as extensive bleeding. Traditional hemostatic methods, such as gauze compression, suturing, and clamping, often carry risks of incomplete hemostasis and postoperative loosening. These risks not only increase surgical complexity but can also adversely affect the patient's recovery and even necessitate a second surgery. To address these issues, a variety of hemostatic materials are now commercially available. While these materials can reduce bleeding to a certain extent, they also present numerous drawbacks. These include slow hemostasis, which increases surgical time, and a lack of self-repair capabilities, making them susceptible to fragmentation and detachment under continued bleeding or organ pulsation, leading to secondary bleeding.
[0003] In recent years, researchers have actively explored new hemostatic materials to address the shortcomings of traditional hemostatic materials. Among them, hydrogels based on polysaccharide polymer networks have attracted widespread attention due to their unique advantages. Hydrogels based on polysaccharide polymer networks are considered to be a research hotspot for the new generation of hemostatic materials due to their advantages such as in situ gelation, good interfacial adhesion, and the ability to load hemostatic and healing factors. However, these hydrogels are still relatively simple in function, with poor mechanical properties such as self-repair, and are not yet comparable to chemically synthesized glues. In addition, their hemostatic efficiency is still insufficient when faced with large amounts of blood loss. These shortcomings limit their application in the field of tissue engineering. Summary of the Invention
[0004] The present invention aims to provide a peach gum-based self-repairing moisturizing hydrogel, a preparation method and its application in hemostatic moisturizing materials. The hydrogel prepared by this preparation method has excellent hemostatic and self-repairing properties, and has good biocompatibility, and can be used for large-area hemostasis of biological tissues such as the liver.
[0005] The first aspect of the present invention provides a method for preparing a peach gum-based self-repairing moisturizing hydrogel, comprising the following steps:
[0006] S1. The purified peach gum was dissolved in PBS buffer, the pH value was adjusted to 5-6 using a pH adjuster, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide were added for activation, and then 3-aminophenylborate hydrochloride was added for reaction. After completion of the reaction, the mixture was dialyzed and freeze-dried to obtain borated peach gum.
[0007] S2. Dissolve borated peach gum in distilled water, then slowly add sodium pyrrolidone carboxylate and mix well to obtain a peach gum-based self-repairing moisturizing hydrogel.
[0008] In some embodiments of the present invention, the preparation method of the purified peach gum is as follows: natural peach gum is soaked, sodium hydroxide is added, the mixture is stirred in a water bath at 60-70°C for 2-4 hours, the mixture is filtered under reduced pressure, the filtrate is taken, concentrated hydrochloric acid is added, the mixture is dialyzed for 3-5 days, and the mixture is freeze-dried to obtain purified peach gum.
[0009] In some embodiments of the present invention, the mass ratio of the natural peach gum to sodium hydroxide is 1g: (8-10)g.
[0010] In some embodiments of the present invention, in step S1, the mass ratio of the purified peach gum, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide is 500 mg: (430-860) mg: (215-430) mg.
[0011] In some embodiments of the present invention, in step S1, the molar ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC•HCl) to N-hydroxysuccinimide (NHS) is (1-2):1.
[0012] In some embodiments of the present invention, in step S1, the mass ratio of the purified peach gum to the 3-aminophenylborate hydrochloride is 500 mg: (175-350) mg.
[0013] In some embodiments of the present invention, in step S1, the pH adjuster is dilute hydrochloric acid.
[0014] In some embodiments of the present invention, in step S1, the activation time is 15 to 30 minutes, and the reaction time is 10 to 12 hours.
[0015] In some embodiments of the present invention, in step S2, the ratio of the borated peach gum, sodium pyrrolidonecarboxylate, and water is 75 mg: 20-30 μL: 800-1200 μL.
[0016] The second aspect of the present invention provides a peach gum-based self-repairing moisturizing hydrogel prepared by the above-mentioned preparation method.
[0017] The third aspect of the present invention provides a peach gum-based hemostatic and moisturizing material, which is obtained by freeze-drying the above-mentioned peach gum-based self-repairing and moisturizing hydrogel.
[0018] A fourth aspect of the present invention provides a use of the peach gum-based self-repairing moisturizing hydrogel or the peach gum-based hemostatic and moisturizing material in preparing a material for hemostasis or moisturizing of biological tissues.
[0019] In some embodiments of the present invention, the application of the peach gum-based hemostatic and moisturizing material in the preparation of a material for hemostasis or moisturizing of biological tissues is specifically as follows: distilled water is added to the peach gum-based hemostatic and moisturizing material until the peach gum-based hemostatic and moisturizing material completely absorbs water to obtain a material for hemostasis or moisturizing of biological tissues, which material is a hydrogel.
[0020] Compared with the prior art, the present invention has the following technical effects:
[0021] (1) The present invention cleverly utilizes the structural and functional properties of natural sodium pyrrolidone carboxylate. By adding sodium pyrrolidone carboxylate to the borated peach gum, the sodium carboxylate groups in the sodium pyrrolidone carboxylate form hydrogen bonds with the hydroxyl groups in the peach gum. On the other hand, the boric acid groups form borate ions in water. The borate ions undergo a nucleophilic substitution reaction with the sodium carboxylate groups, and the boron atoms combine with the oxygen atoms in the carboxylate groups to form borate ester bonds, which are then cross-linked into a gel. Therefore, the construction of a natural peach gum-based hydrogel and its multifunctionality of self-repair, hemostasis, and moisturizing can be achieved by simply mixing the raw materials without the need for a freeze-drying process, thus solving the bottleneck problem of natural materials having a single function and poor mechanical properties.
[0022] (2) The sodium pyrrolidone carboxylate in the present invention has a hygroscopic function. When used as a hemostatic moisturizing glue for hemostasis, it can better absorb wound exudate. Working together with borated peach gum, it can further promote local blood coagulation in the wound and improve the hemostatic efficiency.
[0023] (3) The boric acid group and boric ester group contained in the present invention can form a covalent bond with the polysaccharide-protein complex on the tissue surface. At the same time, sodium pyrrolidonecarboxylate forms an extremely thin hydration layer after absorbing moisture, avoiding the debonding problem caused by the water film of traditional adhesives and enhancing the tissue adhesion effect. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] To more clearly illustrate the technical solution of the present invention, the following briefly introduces the drawings required for use in the embodiments or descriptions of the prior art. Obviously, the drawings described below are only some embodiments of the present invention, and those skilled in the art can derive other drawings based on these drawings without inventive effort.
[0025] Figure 1Schematic diagram of the self-repairing of the peach gum-based self-repairing hemostatic and moisturizing glue prepared in Example 1; Figure A is a schematic diagram of cutting the moisturizing glue; Figure B is a schematic diagram of the moisturizing glue healing after 30 seconds; and Figure C is a schematic diagram of lifting the self-healing glue with tweezers to verify its self-repairing effect.
[0026] Figure 2 Schematic diagram of the hemostatic effect of the self-repairing hemostatic and moisturizing glue on the liver prepared in Example 2; Figure A is a schematic diagram of a liver wound without the use of the bioglue; Figure B is a schematic diagram of a liver wound with the use of the bioglue. DETAILED DESCRIPTION
[0027] The following will be combined with the accompanying drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments of this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.
[0028] An embodiment of the first aspect of the present invention provides a method for preparing a peach gum-based self-repairing moisturizing hydrogel, the preparation method comprising the following steps:
[0029] S1. Dissolve the purified peach gum in PBS buffer, adjust the pH to 5-6, add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide for activation, then add 3-aminophenylborate hydrochloride for reaction. After the reaction is complete, dialyze and freeze-dry to obtain borated peach gum.
[0030] S2. Dissolve borated peach gum in distilled water, slowly add sodium pyrrolidone carboxylate, and mix well to obtain a peach gum-based self-repairing moisturizing hydrogel.
[0031] In step S1, the purified peach gum is dissolved in PBS buffer, the pH value is adjusted to 5-6 using a pH regulator, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide are added to activate the carboxyl groups on the peach gum, and then 3-aminophenylborate hydrochloride is added to react so that the carboxyl groups are combined with the amino groups to form an amide bond, wherein the amounts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide and 3-aminophenylborate hydrochloride are determined according to the number of carboxyl groups in the peach gum. After the reaction is completed, dialysis is performed to remove impurities, and the product is freeze-dried to obtain borated peach gum.
[0032] Exemplarily, purified peach gum refers to peach gum obtained through impurity removal. Exemplarily, peach gum can be purified using sodium hydroxide. The specific method is as follows: natural peach gum is soaked in water, then sodium hydroxide is added, stirred in a water bath at 60-70°C for 2-4 hours, filtered under reduced pressure, the filtrate is collected, concentrated hydrochloric acid is added, dialyzed for 3-5 days, and freeze-dried to obtain purified peach gum. The concentrated hydrochloric acid is used to neutralize the residual sodium hydroxide in the solution.
[0033] Exemplarily, the pH adjuster is dilute hydrochloric acid, preferably having a concentration of 0.010 to 0.012 mol / L.
[0034] Exemplarily, the mass ratio of purified peach gum, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, and N-hydroxysuccinimide is 500:(430-860):(215-430). The molar ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC•HCl) to N-hydroxysuccinimide (NHS) is preferably (1-2):1.
[0035] Exemplarily, the mass ratio of the purified peach gum to the 3-aminophenylborate hydrochloride is 500:(175-350).
[0036] Exemplarily, in step S1, freeze drying is specifically: freezing at -80°C overnight, and then placing in a freeze dryer (-50°C) for freeze drying for 3 days.
[0037] In step S2, the borated peach gum is dissolved in distilled water, and sodium pyrrolidone carboxylate is slowly added and mixed evenly. On the one hand, the sodium carboxylate group in sodium pyrrolidone carboxylate forms a hydrogen bond with the hydroxyl group in the peach gum. On the other hand, the boric acid group modified on the peach gum forms a borate ion in water. The borate ion undergoes a nucleophilic substitution reaction with the sodium carboxylate group, and the boron atom combines with the oxygen atom in the carboxylate to form a borate ester bond, which is cross-linked into a gel to obtain a peach gum-based self-repairing moisturizing hydrogel.
[0038] For example, the mass ratio of borated peach gum to sodium pyrrolidonecarboxylate and water is 75 mg: (20-30) μL: (800-1200) μL.
[0039] The embodiment of the second aspect of the present invention further provides a peach gum-based self-repairing moisturizing hydrogel, which has excellent hemostatic and self-repairing properties.
[0040] The embodiment of the third aspect of the present invention further provides a peach gum-based hemostatic and moisturizing material, which is obtained by mixing borated peach gum, sodium pyrrolidone carboxylate and water.
[0041] An embodiment of the third aspect of the present invention further provides a peach gum-based hemostatic and moisturizing material, which is obtained by freeze-drying a peach gum-based self-repairing and moisturizing hydrogel.
[0042] Exemplarily, the peach gum-based self-repairing moisturizing hydrogel was frozen at -80°C overnight and then placed in a freeze dryer (-50°C) for freeze drying for 3 days to obtain a peach gum-based hemostatic moisturizing material.
[0043] An embodiment of the fourth aspect of the present invention further provides a use of the above-mentioned peach gum-based self-repairing moisturizing hydrogel or the above-mentioned peach gum-based hemostatic and moisturizing material in the preparation of a material for hemostasis or moisturizing of biological tissues.
[0044] Exemplarily, water is added dropwise to the peach gum-based hemostatic and moisturizing material, and the freeze-dried peach gum-based hemostatic and moisturizing material is allowed to completely absorb water to obtain a material for hemostasis or moisturizing of biological tissues.
[0045] Exemplarily, the usage ratio of peach gum-based hemostatic and moisturizing material to water is (49-55) mg:1 mL.
[0046] In order to further illustrate the embodiments of the present application, the following is a detailed description of the embodiments and the appended drawings. Figure 1 、 Figure 2 The hydrogel for tissue repair and the preparation method thereof in the embodiments of the present application are described in detail.
[0047] Preparation of the purified peach gum used in the embodiment:
[0048] 1035 mg of natural peach gum was placed in 100 ml of distilled water and soaked for 24 h. 8046 mg of sodium hydroxide was added and stirred in a 60°C water bath for 2 h. Impurities were removed by filtration under reduced pressure. 16 mL of 0.012 mol / mL hydrochloric acid was added and dialyzed for 3 days. The purified peach gum was freeze-dried to obtain the purified peach gum.
[0049] Example 1
[0050] 1) Weigh 500 mg of purified peach gum and dissolve it in 100 mL of calcium- and magnesium-free PBS buffer. Adjust the pH to 5 with 0.010 mol / mL hydrochloric acid. Add 430 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC•HCl) and 215 mg of N-hydroxysuccinimide (NHS) to activate the peach gum solution for 15 minutes. Add 175 mg of 3-aminophenylborate hydrochloride and react for 12 hours. Dialyze for 3 days and freeze-dry to obtain borated peach gum (PR-3APBA).
[0051] 2) Weigh 75 mg of PR-3APBA and dissolve it in 1000 μL of distilled water. Add 20 μL of sodium pyrrolidonecarboxylate and mix well to obtain a peach gum-based self-healing hemostatic and moisturizing gel.
[0052] Verify the self-repairing ability of peach gum-based self-repairing hemostatic moisturizing glue, the results are as follows Figure 1 shown.
[0053] The peach gum-based self-repairing hemostatic and moisturizing glue obtained in Example 1 was cut into two parts using a scalpel. Figure 1 As shown in A; then put the separated peach gum-based self-repairing hemostatic moisturizing glue together and wait for about 30 seconds. Figure 1 As shown in B, the separated glue undergoes self-repair and healing; then the peach gum-based self-repair hemostatic and moisturizing glue is lifted up with tweezers, as shown in FIG. Figure 1 As shown in C, the healed peach gum-based self-repairing hemostatic and moisturizing glue remained intact after being lifted and did not separate, indicating that self-repair occurred.
[0054] 3) The peach gum-based self-repairing hemostatic and moisturizing gel obtained in step 2) was frozen at -80°C overnight, and then freeze-dried in a freeze dryer (-50°C) for 3 days to obtain a freeze-dried block.
[0055] 4) Weigh 55 mg of the freeze-dried cake and add 1 mL of distilled water. Wait until the freeze-dried cake completely absorbs the water to obtain the hydrogel.
[0056] Example 2
[0057] 1) Weigh 500 mg of purified peach gum and dissolve it in 100 mL of calcium- and magnesium-free PBS buffer. Adjust the pH to 5 with 0.011 mol / mL hydrochloric acid. Add 645 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC•HCl) and 322 mg of N-hydroxysuccinimide (NHS) to activate the peach gum solution for 15 minutes. Add 262 mg of 3-aminophenylborate hydrochloride and react for 12 hours. Dialyze for 3 days and freeze-dry to obtain borated peach gum (PR-3APBA).
[0058] 2) Weigh 75 mg of PR-3APBA and dissolve it in 1000 μL of distilled water. Add 25 μL of sodium pyrrolidonecarboxylate and mix well to obtain a peach gum-based self-healing hemostatic and moisturizing gel.
[0059] Verify the hemostatic ability of peach gum-based self-repairing hemostatic moisturizing glue, the results are as follows Figure 2 shown.
[0060] 8-week-old SD rats weighing 218 g were anesthetized with 20% urethane. The abdominal cavity was opened and the left lobe of the liver was pulled out. A piece of filter paper was placed under it. A 1 cm long and 2 mm deep incision was made on the left lobe with a scalpel. The blank group was treated as follows. Figure 2 As shown in A, bleeding continued within 1 minute, and the blood continued to spread on the filter paper; the hemostatic effect of peach gum-based self-repairing hemostatic moisturizing glue is as follows Figure 2 As shown in B, after the wound was sealed with glue, bleeding stopped within 1 minute, and there was no blood stain on the filter paper, indicating that the amount of bleeding was low and the bleeding was successfully stopped.
[0061] 3) The peach gum-based self-repairing hemostatic and moisturizing gel obtained in step 2) was frozen at -80°C overnight, and then freeze-dried in a freeze dryer (-50°C) for 3 days to obtain a freeze-dried block.
[0062] 4) Weigh 49 mg of the freeze-dried cake and add 1 mL of distilled water. Wait until the freeze-dried cake completely absorbs the water to obtain the hydrogel.
[0063] Example 3
[0064] 1) Weigh 500 mg of purified peach gum and dissolve it in 100 mL of calcium- and magnesium-free PBS buffer. Adjust the pH to 5 with 0.012 mol / mL hydrochloric acid. Add 860 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC•HCl) and 430 mg of N-hydroxysuccinimide (NHS) to activate the peach gum solution for 15 minutes. Add 350 mg of 3-aminophenylborate hydrochloride and react for 12 hours. Dialyze for 3 days and freeze-dry to obtain borated peach gum (PR-3APBA).
[0065] 2) Weigh 75 mg of PR-3APBA and dissolve it in 1000 μL of distilled water. Add 30 μL of sodium pyrrolidonecarboxylate and mix thoroughly to obtain a peach gum-based self-healing hemostatic and moisturizing gel.
[0066] 3) The peach gum-based self-repairing hemostatic and moisturizing gel obtained in step 2) was frozen at -80°C overnight, and then freeze-dried in a freeze dryer (-50°C) for 3 days to obtain a freeze-dried block.
[0067] 4) Weigh 52 mg of freeze-dried cake and add 1 mL of distilled water. Wait until the freeze-dried cake completely absorbs the water to obtain the hydrogel.
[0068] Comparative Example 1
[0069] The amount of sodium pyrrolidonecarboxylate in step 2) of Example 1 was changed to 18 μL and stirred evenly, but no hydrogel was formed.
[0070] Comparative Example 1
[0071] The amount of sodium pyrrolidonecarboxylate in step 2) of Example 1 was changed to 33 μL and stirred evenly, but no hydrogel could be formed.
[0072] Comparative Example 3
[0073] 1) Dissolve 100 mg of gelatin in 1 mL of distilled water in a 70°C water bath. Add 52 μL of sodium pyrrolidonecarboxylate and mix thoroughly to obtain a mixed solution. Allow the mixed solution to stand for a period of time. The solution should remain in solution.
[0074] 2) The mixed solution was freeze-dried to obtain a freeze-dried cake, into which 1 mL of distilled water was added dropwise to obtain a gelatin-pyrrolidone carboxylic acid nanohydrogel.
[0075] Comparative Examples 1-2 show that when the amount of sodium pyrrolidonecarboxylate used is too much or too little, no hydrogel can be formed.
[0076] The above description fully discloses the specific embodiments of the present invention. It should be noted that any modifications made by those skilled in the art to the specific embodiments of the present invention do not depart from the scope of the claims. Accordingly, the scope of the claims of the present invention is not limited solely to the foregoing specific embodiments.
Claims
1. A method for preparing a peach gum-based self-repairing moisturizing hydrogel, characterized in that: The preparation method comprises the following steps: S1. The purified peach gum was dissolved in PBS buffer, the pH value was adjusted to 5-6 using a pH adjuster, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide were added for activation, and then 3-aminophenylborate hydrochloride was added for reaction. After completion of the reaction, the mixture was dialyzed and freeze-dried to obtain borated peach gum. S2. Dissolve borated peach gum in distilled water, slowly add sodium pyrrolidone carboxylate, and mix well to obtain a peach gum-based self-repairing moisturizing hydrogel.
2. The preparation method according to claim 1, characterized in that The preparation method of the purified peach gum comprises the following steps: soaking natural peach gum in water, adding sodium hydroxide, stirring in a water bath at 60-70° C. for 2-4 hours, filtering under reduced pressure, taking the filtrate, adding concentrated hydrochloric acid, dialyzing for 3-5 days, and freeze-drying to obtain the purified peach gum.
3. The preparation method according to claim 1, characterized in that In step S1, the pH adjuster is dilute hydrochloric acid.
4. The preparation method according to claim 1, characterized in that In step S1, the mass ratio of the purified peach gum, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide is 500 mg: (430-860) mg: (215-460) mg.
5. The preparation method according to claim 1, characterized in that In step S1, the mass ratio of the purified peach gum to the 3-aminophenylborate hydrochloride is 500 mg: (175-350) mg.
6. The preparation method according to claim 1, characterized in that In step S1, the activation time is 15 to 30 minutes, and the reaction time is 10 to 12 hours.
7. The preparation method according to claim 1, characterized in that In step S2, the ratio of the borated peach gum, sodium pyrrolidonecarboxylate and water is: 75 mg: (20-30) μL: 1000 μL.
8. A peach gum-based self-repairing moisturizing hydrogel prepared according to the preparation method according to any one of claims 1 to 7.
9. A peach gum-based hemostatic and moisturizing material, characterized in that: The peach gum-based hemostatic and moisturizing material is obtained by freeze-drying the peach gum-based self-repairing and moisturizing hydrogel according to claim 8.
10. Use of the peach gum-based self-repairing moisturizing hydrogel according to claim 8 or the peach gum-based hemostatic moisturizing material according to claim 9 in preparing a material for hemostasis or moisturizing of biological tissues.