PH intelligent response Se quantum dot polysaccharide hydrogel as well as preparation method and medical application thereof
By preparing pH-responsive Se quantum dot polysaccharide hydrogels, the problems of traditional dressings being unable to maintain a moist environment and lacking pH monitoring in the treatment of diabetic wounds have been solved. This has enabled close adhesion to the wound and real-time pH monitoring, thereby improving the healing effect of diabetic wounds.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- NANTONG UNIV
- Filing Date
- 2026-03-18
- Publication Date
- 2026-05-05
AI Technical Summary
Existing traditional dressings cannot effectively maintain a moist environment for diabetic wounds, are prone to adhering to newly formed granulation tissue, increasing the risk of infection, and lack real-time monitoring of wound healing pH, which limits their application in the treatment of diabetic wounds.
A pH-responsive Se quantum dot polysaccharide hydrogel was prepared. By forming a hydrophobic inclusion complex through the structural characteristics of gelatin and gum arabic, and utilizing the fluorescence responsiveness of selenium quantum dots, dynamic monitoring of wound pH and self-healing performance were achieved.
This hydrogel can closely adhere to the wound, providing self-healing properties, and monitors the wound pH value through fluorescence response, reducing the risk of infection and optimizing the healing environment.
Smart Images
Figure CN121971691A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomedical materials technology, and relates to a pH-responsive Se quantum dot polysaccharide hydrogel, its preparation method, and its pharmaceutical applications. Background Technology
[0002] Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia, microvascular complications leading to tissue hypoxia, oxidative stress, and persistent inflammation, often resulting in metabolic disorders. Diabetic wounds (such as diabetic foot ulcers) are a common complication. For a healthy body, wound healing is an orderly process involving four stages: hemostasis, inflammation, proliferation, and remodeling. However, various pathological factors in diabetic patients disrupt this process. Clinically, traditional dressings can provide physical isolation for routine acute wounds. However, for chronic, difficult-to-heal wounds caused by diabetes, traditional dressings not only fail to maintain a moist environment conducive to healing but also easily adhere to newly formed granulation tissue during dressing changes, leading to "secondary damage" and increasing the risk of infection. Furthermore, the management of chronic wound healing faces many challenges, such as increased bacterial resistance and the difficulty in real-time monitoring of the wound microenvironment (pH value).
[0003] In recent years, researchers have actively explored and developed novel medical bio-adhesives and functional hydrogel dressings to address the shortcomings of traditional dressings. Replacing traditional dry dressings with bioactive materials is a new approach to achieving moist wound healing. In clinical treatment, their excellent adhesion and self-healing properties are being utilized to fill irregular wounds, optimizing the regenerative microenvironment and reducing wound infection rates. Furthermore, single treatment modalities cannot provide real-time feedback on wound healing status. For example, dynamic changes in pH are directly related to bacterial infection and angiogenesis; the lack of real-time monitoring of such key indicators often delays optimal treatment. However, most commercially available products are currently made of chemically synthesized materials, and their poor biocompatibility and gaps leading to bacterial growth due to incomplete adhesion to complex wounds remain significant issues. Moreover, the lack of feedback capability regarding pH changes during wound healing limits their further application in precision medicine.
[0004] Therefore, developing a composite hydrogel that integrates good biocompatibility, tight adhesion to complex wounds, and visualized pH monitoring is of great clinical significance for overcoming the bottleneck in the treatment of diabetic wounds. Summary of the Invention
[0005] In view of this, the present invention aims to provide a pH-responsive Se quantum dot polysaccharide hydrogel, its preparation method and its medical applications. The hydrogel has excellent self-healing properties, good biocompatibility and pH monitoring function, and can be applied to the monitoring and treatment of pH in skin lesions such as diabetic wounds.
[0006] In a first aspect, the present invention provides a method for preparing a pH-responsive Se quantum dot polysaccharide hydrogel, characterized in that the preparation method includes the following steps:
[0007] S1. Sodium carboxymethyl-β-cyclodextrin was activated using 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide; subsequently, the activated product was mixed with a gelatin solution and reacted. After the reaction was completed, the product was dialyzed and freeze-dried to obtain cyclodextrin gelatin.
[0008] S2. After dissolving peach gum in water, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide were added for activation treatment. Then, adamantane was added to the reaction system for reaction. After the reaction was completed, the resulting reaction solution was dialyzed and freeze-dried to obtain adamantane peach gum.
[0009] S3. Add cyclodextrin gelatin and adamantane gum to water containing selenium quantum dots, stir and let stand to obtain pH-responsive Se quantum dot polysaccharide hydrogel.
[0010] In some embodiments of the present invention, in step S1, the mass ratio of gelatin, sodium carboxymethyl-β-cyclodextrin, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, and N-hydroxysuccinimide is 1000:(2200-2500):(1800-1900):(1000-1200).
[0011] In some embodiments of the present invention, in step S1, the activation time is 15 to 30 minutes and the reaction time is 8 to 12 hours.
[0012] In some embodiments of the present invention, in step S2, the mass ratio of peach gum, adamantane, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, and N-hydroxysuccinimide is 1000:(500-600):(900-950):(500-600).
[0013] In some embodiments of the present invention, in step S2, the activation time is 15 to 30 minutes and the reaction time is 8 to 12 hours.
[0014] In some embodiments of the present invention, the dialysis time is 3-5 days.
[0015] In some embodiments of the present invention, the freeze-drying specifically involves: after being kept at -80°C overnight, the product is directly placed in a freeze dryer and freeze-dried for approximately 3 days.
[0016] In some embodiments of the present invention, in step S3, the ratio of cyclodextrin gelatin, adamantane gum, selenium quantum dots and water is (120-140) mg: (40-50) mg: (6-12) mg: 1000 mL.
[0017] A second aspect of the present invention provides a pH-responsive Se quantum dot polysaccharide hydrogel prepared according to the above-described preparation method.
[0018] A third aspect of the present invention provides the application of the above-described pH-responsive Se quantum dot polysaccharide hydrogel in the preparation of materials for pH monitoring or repair of skin damage.
[0019] In a fourth aspect, the present invention provides a pH-responsive material obtained by dehydrating and drying the aforementioned pH-responsive Se quantum dot polysaccharide hydrogel. This material exhibits reversible hydration properties, and can re-swell to form a hydrogel by immersion in water.
[0020] Compared with the prior art, the present invention has the following technical effects:
[0021] (1) This invention cleverly utilizes the structural and functional properties of gelatin and peach gum. Cyclodextrin grafted onto the gelatin chain and adamantane grafted onto the peach gum chain form a specific hydrophobic inclusion complex. The β-cyclodextrin cavity on the gelatin chain will quickly recognize and capture the adamantane group on the peach gum chain. Based on hydrophobic interaction and van der Waals force, the material is endowed with excellent bioactivity and self-healing properties.
[0022] (2) The fluorescence intensity of the selenium quantum dots of the present invention is pH responsive. The surface ligands undergo protonation or deprotonation under different acid and alkaline conditions, thereby exciting fluorescence responses of different intensities, which can realize dynamic monitoring of pH value at the site of skin injury.
[0023] (3) The hydrogel in this invention has excellent self-healing properties before application, making it easy to fill irregular wounds. When applied to the gaps in skin damage, it can adhere firmly to the skin damage site, ensuring that the dressing fits tightly to the wound. Attached Figure Description
[0024] 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.
[0025] Figure 1The self-healing properties of the pH-responsive Se quantum dot polysaccharide hydrogel prepared in Example 1 are shown; Figure A is a schematic diagram of the hydrogel being cut open; Figure B is a schematic diagram of the hydrogel healing into a whole after 30 seconds.
[0026] Figure 2 The changes in fluorescence intensity of the pH-responsive Se quantum dot polysaccharide hydrogel prepared in Example 2 at different pH values are shown. Detailed Implementation
[0027] 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.
[0028] Example 1
[0029] 1) Weigh 2200 mg of sodium carboxymethyl-β-cyclodextrin and dissolve it in 5 mL of distilled water. Add 1800 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1000 mg of N-hydroxysuccinimide. After activating for 15 minutes, add it to a 1000 mg gelatin solution dissolved in 100 mL of distilled water. React for 10 hours, dialyze for 3 days, and freeze dry to obtain cyclodextrin gelatin.
[0030] 2) Weigh 1000mg of peach gum and dissolve it in 100mL of distilled water. Add 900mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 500mg of N-hydroxysuccinimide. Activate for 15 minutes, add 500mg of adamantane, react for 8 hours, dialyze for 3 days, and freeze at -80°C overnight. Then freeze dry for about 3 days to obtain adamantane-containing peach gum.
[0031] 3) Weigh 120 mg of cyclodextrin gelatin and 6 mg of selenium quantum dots and dissolve them in 500 μL of distilled water; weigh 40 mg of adamantane gum and dissolve it in 500 μL of distilled water. Mix them evenly, stir, and let them stand to obtain pH-responsive Se quantum dot polysaccharide hydrogel.
[0032] To verify the self-healing ability of the pH-responsive Se quantum dot polysaccharide hydrogel, the pH-responsive Se quantum dot polysaccharide hydrogel obtained in Example 1 was cut into two equal parts using a scalpel and then reassembled. The healing process was observed, and the results are as follows: Figure 1 As shown. Figure 1In the image, Figure A shows a photograph of the hydrogel being cut into two equal parts using a scalpel; Figure B shows a photograph taken after 30 seconds of observation. It can be seen that the cut hydrogel pieces were put back together and self-healed after 30 seconds, indicating excellent self-healing performance.
[0033] Example 2
[0034] 1) Weigh 2500 mg of sodium carboxymethyl-β-cyclodextrin and dissolve it in 5 mL of distilled water. Add 1800 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1000 mg of N-hydroxysuccinimide and activate for 15 minutes. Then add it to a 1000 mg gelatin solution dissolved in 100 mL of distilled water. React for 12 hours, dialyze for 3 days, and freeze dry to obtain cyclodextrin gelatin.
[0035] 2) Weigh 1000mg of peach gum and dissolve it in 100mL of distilled water. Add 950mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 600mg of N-hydroxysuccinimide and activate for 15 minutes. Add 600mg of adamantane and react for 8 hours. Dialyze for 3 days and freeze at -80°C overnight. Then freeze dry for about 3 days to obtain adamantane-containing peach gum.
[0036] 3) Weigh 120 mg of cyclodextrin gelatin and 12 mg of selenium quantum dots and dissolve them in 500 μL of distilled water; weigh 40 mg of adamantane gum and dissolve it in 500 μL of distilled water. Mix them evenly, stir, and let them stand to obtain pH-responsive Se quantum dot polysaccharide hydrogel.
[0037] To verify the pH monitoring capability of the pH-responsive Se quantum dot polysaccharide hydrogel, the hydrogel was added to PBS solutions with different pH values (pH=4, 5, 6, 7, 8, 9). The changes in fluorescence intensity of the hydrogel at different pH values were recorded using a fluorescence spectrophotometer. Figure 2 As shown, the fluorescence intensity of the hydrogel varies significantly at different pH values.
[0038] Example 3
[0039] 1) Weigh 2200 mg of sodium carboxymethyl-β-cyclodextrin and dissolve it in 5 mL of distilled water. Add 1800 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 1000 mg of N-hydroxysuccinimide and activate for 15 minutes. Then add it to a 1000 mg gelatin solution dissolved in 100 mL of distilled water. React for 10 hours, dialyze for 3 days, and freeze dry to obtain cyclodextrin gelatin.
[0040] 2) Weigh 1000mg of peach gum and dissolve it in 100mL of distilled water. Add 900mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 500mg of N-hydroxysuccinimide and activate for 15 minutes. Add 500mg of adamantane and react for 8 hours. Dialyze for 3 days and then freeze at -80℃ overnight. Then freeze dry for about 3 days to obtain adamantane-containing peach gum.
[0041] 3) Weigh 120 mg of cyclodextrin gelatin and 6 mg of selenium quantum dots and dissolve them in 500 μL of distilled water; weigh 40 mg of adamantane gum and dissolve it in 500 μL of distilled water. Mix them evenly, stir, and let them stand to obtain pH-responsive Se quantum dot polysaccharide hydrogel.
[0042] To verify the flowability of the pH-responsive Se quantum dot polysaccharide hydrogel, the pH-responsive Se quantum dot polysaccharide hydrogel obtained in Example 3 was loaded into a 1 mL syringe. The hydrogel was able to be smoothly extruded through the syringe, forming a continuous and complete letter structure without any breakage or collapse, indicating that the hydrogel has excellent flowability.
[0043] Example 4
[0044] When the amounts of sodium carboxymethyl-β-cyclodextrin and adamantane in steps 1 and 2) of Example 1 were replaced with 2500 mg and 600 mg respectively, the hydrogel exhibited good self-healing properties. This indicates that the amounts of sodium carboxymethyl-β-cyclodextrin and adamantane do not affect the excellent self-healing properties of the hydrogel.
[0045] Example 5
[0046] When the amount of Se quantum dots in step 3) of Example 1 was changed to 12 mg, the hydrogel still had the pH detection effect, indicating that the amount of Se quantum dots does not affect the pH monitoring effect of the hydrogel.
[0047] 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 pH-responsive Se quantum dot polysaccharide hydrogel, characterized in that, The preparation method includes the following steps: S1. Sodium carboxymethyl-β-cyclodextrin was activated using 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide; subsequently, the activated product was mixed with a gelatin solution and reacted. After the reaction was completed, the product was dialyzed and freeze-dried to obtain cyclodextrin gelatin. S2. After dissolving peach gum in water, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide were added for activation treatment. Then, adamantane was added to the reaction system for reaction. After the reaction was completed, the resulting reaction solution was dialyzed and freeze-dried to obtain adamantane peach gum. S3. Add cyclodextrin gelatin and adamantane gum to water containing selenium quantum dots, stir and let stand to obtain pH-responsive Se quantum dot polysaccharide hydrogel.
2. The preparation method according to claim 1, characterized in that, In step S1, the mass ratio of gelatin, sodium carboxymethyl-β-cyclodextrin, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, and N-hydroxysuccinimide is 1000:(2200-2500):(1800-1900):(1000-1200).
3. The preparation method according to claim 2, characterized in that, In step S1, the activation time is 15–30 minutes, and the reaction time is 8–12 hours.
4. The preparation method according to claim 1, characterized in that, In step S2, the mass ratio of peach gum, adamantane, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, and N-hydroxysuccinimide is 1000:(500-600):(900-950):(500-600).
5. The preparation method according to claim 4, characterized in that, In step S2, the activation treatment time is 15 to 30 minutes, and the reaction time is 8 to 12 hours.
6. The preparation method according to claim 1, characterized in that, The dialysis period is 3-5 days.
7. The preparation method according to claim 1, characterized in that, In step S3, the ratio of cyclodextrin gelatin, adamantane gum, selenium quantum dots and water is (120-140) mg: (40-50) mg: (6-12) mg: 1000 mL.
8. A pH-responsive Se quantum dot polysaccharide hydrogel prepared by the preparation method according to any one of claims 1-7.
9. The application of the pH-responsive Se quantum dot polysaccharide hydrogel as described in claim 8 in the preparation of materials for pH monitoring or repair of skin damage.
10. A pH-smart responsive material, characterized in that, The pH-responsive material is obtained by dehydration and drying of the pH-responsive Se quantum dot polysaccharide hydrogel as described in claim 8.