Preparation method of dendrophenol-glycyrrhizic acid self-assembled gel spray as well as product and application of dendrophenol-glycyrrhizic acid self-assembled gel spray

Abstract

The invention discloses a preparation method of dendrophenol-glycyrrhizic acid self-assembled gel spray as well as a product and application thereof, and belongs to the field of new medical application of active ingredients of traditional Chinese medicinal materials. The preparation method comprises the following steps: preparing dendrophenol-glycyrrhizic acid self-assembled nanoparticles by taking dendrophenol and glycyrrhizic acid as raw materials, mixing the nanoparticles with chitosan, adding a cross-linking agent, and further preparing into a gel spray dosage form. Experimental results show that the gel spray has good biocompatibility and remarkable antibacterial performance, inflammatory response and epidermis thickening of a mouse allergic skin disease model induced by 2, 4-dinitrochlorobenzene can be effectively inhibited, scratching behaviors are reduced, skin tissue inflammation and oxidative stress injury are relieved, and the gel spray has a good application prospect. The infiltration of eosinophilic granulocytes and mast cells at the affected part is reduced, and the immune balance is regulated. The product obtained by the invention has various effects of resisting allergic reaction, diminishing swelling, relieving itching and the like, and has a good application prospect in the aspect of treatment of allergic skin diseases.

Description

Technical Field

[0001] This invention relates to the field of new pharmaceutical applications of dendrobium, an active ingredient in traditional Chinese medicine, specifically to the preparation of dendrobium-glycyrrhizic acid self-assembled gel spray and its application in treating allergic skin diseases, including urticaria, eczema, contact dermatitis, atopic dermatitis, allergic purpura, and drug eruption. Background Technology

[0002] Allergic skin diseases are common clinical conditions, primarily manifesting as dermatitis, eczema, and urticaria mediated by type I hypersensitivity reactions. The core pathological mechanism involves allergens inducing telangiectasia, inflammatory cell infiltration, and nerve ending stimulation, leading to symptoms such as erythema, ulceration, and intense itching, severely impacting patients' quality of life. Currently, first-line clinical treatment mainly involves topical corticosteroids and calcineurin inhibitors (such as tacrolimus). However, long-term use has significant limitations. For example, corticosteroids can easily induce skin atrophy and telangiectasia, while calcineurin inhibitors carry a potential risk of lymphoma. Both can also inhibit the synthesis and secretion of antimicrobial peptides in the skin, increasing the risk of secondary infections. Because allergic skin diseases require long-term intervention, the aforementioned safety concerns and the high cost of some medications result in generally low patient adherence.

[0003] Natural active ingredients such as dendrobine and glycyrrhizic acid possess multi-target regulatory potential, exhibiting good activity in anti-inflammatory, antibacterial, and immunomodulatory effects. However, their low water solubility, poor chemical stability, and weak skin penetration limit their effective delivery and application in traditional dosage forms. Existing hydrogel carriers generally suffer from low encapsulation efficiency and insufficient mechanical strength when encapsulating hydrophobic drugs, leading to drug burst release, which is insufficient to meet the needs of multi-pathway synergistic therapy such as immunomodulation, antibacterial, and antioxidant effects. Therefore, developing a novel formulation that can improve drug stability, achieve responsive release in the lesion microenvironment, avoid the side effects of hormonal drugs, and is cost-effective has become a core issue that urgently needs to be addressed in the treatment of allergic skin diseases. Summary of the Invention

[0004] Purpose of the invention: This invention provides a gel for allergic skin diseases that combines efficient drug delivery, pH-responsive release, and synergistic functions of antibacterial, antioxidant, and immunomodulatory effects, thereby solving the problems of low delivery efficiency of natural drugs and significant side effects in the treatment of allergic skin diseases.

[0005] Another technical problem to be solved by the present invention is to provide a method for preparing dendrobium phenol-glycyrrhizic acid self-assembled gel.

[0006] The final technical problem to be solved by this invention is to provide the application of the above-mentioned dendrobium phenol-glycyrrhizic acid self-assembled gel in the preparation of a treatment for allergic skin diseases.

[0007] Technical Solution: To solve the above-mentioned technical problems, the present invention provides the following technical solution: A method for preparing dendrobium phenol-glycyrrhizic acid self-assembled gel involves preparing dendrobium phenol-glycyrrhizic acid self-assembled nanoparticles using dendrobium phenol and licorice, mixing the dendrobium phenol-glycyrrhizic acid self-assembled nanoparticles with chitosan, and then adding a crosslinking agent to obtain a dendrobium phenol-glycyrrhizic acid nanoparticle / chitosan / dextran hydrogel.

[0008] The preparation method of the dendrobium phenol-glycyrrhizic acid self-assembled nanoparticles is as follows: Dendrobium phenol and glycyrrhizic acid were dissolved in dimethyl sulfoxide, and then the mixture was added dropwise to water, stirred, dialyzed, and freeze-dried to obtain dendrobium phenol-glycyrrhizic acid self-assembled nanoparticle powder.

[0009] Furthermore, dendrobine and glycyrrhizic acid are mixed in a molar ratio of 1:2 to 2:1, with 1:1 being the most preferred.

[0010] Furthermore, the hydrogel solid content is from 5 wt% to 20 wt%.

[0011] Furthermore, the mass ratio of dendrobium phenol-glycyrrhizic acid self-assembled nanoparticles to chitosan is 1:1 to 20:1, with the most preferred ratio being 11.27:10.

[0012] Furthermore, the chitosan described is a chitosan modified with catechin.

[0013] Furthermore, the method for preparing the catechin-modified chitosan is as follows: chitosan is reacted with grafted 3,4-dihydroxyphenylpropionic acid to obtain catechin-modified chitosan; The ratio of chitosan to grafted 3,4-dihydroxyphenylpropionic acid is 10:5 to 1:3 by mass, with the most preferred ratio being 5:3.21.

[0014] Furthermore, the crosslinking agent is a polyaldehyde dextran, and the degree of oxidation of the polyaldehyde dextran is 40%~60%. Oxidized dextran is prepared using conventional methods, such as oxidizing dextran with sodium periodate in an ethanol / water solvent. An oxidation degree of 40%-60% for the aldehyde groups is preferred. Too low an oxidation degree results in insufficient crosslinking, while too high an oxidation degree leads to excessively high toxicity of the component, affecting its further application in vivo.

[0015] The dendrobium-glycyrrhizic acid self-assembled gel prepared by the above-described method is within the scope of protection of this invention.

[0016] The above-mentioned dendrobium phenol-glycyrrhizic acid self-assembled gel is used in the preparation of drugs for treating allergic skin diseases, including urticaria, eczema, contact dermatitis, atopic dermatitis, allergic purpura, and drug eruption.

[0017] Beneficial Effects: Compared with existing topical preparations for atopic dermatitis, the dendrobium phenol-glycyrrhizic acid self-assembled gel spray provided by this invention achieves significant improvements in efficacy, safety, and industrialization feasibility. This invention has the following significant advancements and advantages: (1) By utilizing the intermolecular hydrogen bonds and hydrophobic interactions between dendrobium and glycyrrhizic acid, uniform nanoparticles of 80-150 nm are self-assembled in the aqueous phase, with a drug encapsulation rate of ≥85% and the particle size and PDI remain constant within one week; compared with free drugs, the water solubility of dendrobium and glycyrrhizic acid is greatly improved.

[0018] (2) Through rheological properties, adhesion and healing ability tests, the material performance tests show that the gel, through the reversible reconstruction of the dynamic bond network, endows the gel spray with excellent rheological adaptability, strong interfacial adhesion and efficient self-healing ability.

[0019] (3) In a mouse AD model, experimental results showed that the gel spray exhibited good wound healing and anti-inflammatory effects during the treatment period, significantly reduced dermatitis scores, improved symptoms such as erythema and edema, and inhibited splenomegaly. In histological analysis, H&E staining of skin tissue sections showed that the gel spray could reduce the number of inflammatory cells and decrease epidermal thickening. TB staining results showed that the gel spray could significantly reduce mast cell infiltration. 8-OHdG staining revealed that the gel spray could effectively scavenge intracellular reactive oxygen species and alleviate oxidative damage to nuclear DNA.

[0020] (4) The dendrobium phenol-glycyrrhizic acid self-assembled gel spray of the present invention significantly improves the symptoms and histopathological features of atopic dermatitis in mice through multiple mechanisms such as promoting wound healing, inhibiting inflammatory response, regulating immune abnormalities and reducing oxidative damage, showing good therapeutic potential. Attached Figure Description

[0021] Figure 1 (A) GD one-cycle particle size data and PDI diagram; (B) GD transmission electron microscope image and built-in inset Tyndall effect diagram.

[0022] Figure 2 (A) Molecular dynamics simulation of GD structural changes (initial and final states); (B) Molecular interaction diagram of the GD system.

[0023] Figure 3 (A) Infrared spectra of Gly, Den, and GD; (B) Infrared spectra of GD Gel.

[0024] Figure 4 (A) Image showing the transformation of GD Gel from sol to gel state; (B) Image showing the adhesion effect of GD Gel on a pigskin substrate; (C) Image showing the healing process of GD Gel on fingers and joints.

[0025] Figure 5 (A) MTT toxicity graph of L929 cells; (B) MTT toxicity graph of RAW264.7 cells; (C) Biosafety graph of GD Gel on L929 cells as determined by Live / Dead dual fluorescence assay (scale bar: 50 μm); (D) Biosafety graph of GD Gel on RAW264.7 cells as determined by Live / Dead dual fluorescence assay (scale bar: 50 μm); Figure 6 . Intracellular reactive oxygen species laser confocal image determined by fluorescent probe method (scale bar: 50 μm).

[0026] Figure 7 The antibacterial properties were evaluated using the plate coating method.

[0027] Figure 8 Before and after photos of AD skin treatment.

[0028] Figure 9 Mouse dermatitis scoring chart.

[0029] Figure 10 (A) H&E staining of skin tissue; (B) Statistical chart of epidermal thickness.

[0030] Figure 11 (A) TB staining image of skin tissue; (B) Statistical diagram of mast cell count.

[0031] Figure 12 (A) 8-OHdG staining image of skin tissue; (B) Statistical graph of 8-OHdG fluorescence intensity.

[0032] Note: Data are expressed as Mean ± SD, n = 5, ns: no significance, * P <0.05,** P <0.01, *** P <0.001, **** P <0.0001. Detailed Implementation

[0033] The following embodiments are further illustrations of the present invention and serve as explanations of the technical content of the present invention. However, the essence of the present invention is not limited to the embodiments described below. Those skilled in the art can and should know that any simple changes or substitutions based on the spirit of the present invention should fall within the protection scope claimed by the present invention.

[0034] Example 1: The preparation method of dendrobium phenol-glycyrrhizic acid self-assembled nanoparticles (GD) is as follows.

[0035] Dendrobium phenol (Den) and glycyrrhizic acid (GA) were weighed and dissolved separately in dimethyl sulfoxide (DMSO). The solutions were vortexed (1500 rpm, 2 min) to prepare a 10 mg / mL stock solution, which was then stored in the dark for later use. 30.4 μL of Den solution was mixed with 82.3 μL of GA solution, and after vortexing for 30 s, the mixture was added dropwise to 2 mL of ultrapure water with magnetic stirring (500 rpm, 25 °C) at a rate of 0.5 mL / min using a peristaltic pump. The mixture was stirred for another 10 min. The mixture was then transferred to a pretreated dialysis bag (MWCO 3000 Da). After dialysis, the solution was freeze-dried to obtain dendrobium phenol-glycyrrhizic acid self-assembled nanoparticles (GD).

[0036] Example 2: Preparation of chitosan grafted with 3,4-dihydroxyphenylpropionic acid (CS-DA).

[0037] (1) Weigh 0.5 g of chitosan and dissolve it in 75 mL of ultrapure water. Stir magnetically to disperse it evenly, add concentrated hydrochloric acid dropwise until completely dissolved, and adjust the pH to 4~6 with 1 M NaOH and 1 M HCl solution.

[0038] (2) Weigh 0.321 g of 3,4-dihydroxyphenylpropionic acid and dissolve it in 3 mL of ultrapure water. Vortex the solution. Add the solution dropwise to the chitosan solution at a rate of 0.5 mL / min using a peristaltic pump and stir continuously with magnetic force while maintaining the pH at 4-6.

[0039] (3) Weigh 0.2725 g of EDC (carbodiimide) and dissolve it in a 1:1 mixture of 6.25 mL of ultrapure water and anhydrous ethanol. Dissolve 0.273 g of EDC in a 1:1 mixture of 6.25 mL of water and ethanol. Vortex at 1500 rpm for 2 min to dissolve the EDC. Then, pump the EDC into the reaction system at a rate of 0.5 mL / min. Immediately maintain the pH at 5 with dilute alkali / acid. React at 600 rpm at room temperature for 8 h. After the reaction is complete, transfer the reaction solution to a dialysis bag (MWCO 3000 Da) for dialyzing (pH=5). After freeze-drying, store the solution in a dry and light-protected environment.

[0040] Preparation of oxidized dextran (ODex): 1 g of dextran (Dex) was accurately weighed and dissolved in 50 mL of ultrapure water. Then, 0.64 g of sodium periodate was accurately added, and the mixture was stirred at room temperature in the dark for 4 h. Subsequently, 1.5 mL of ethylene glycol was added, and stirring was continued for 1 h to terminate the oxidation reaction. The reaction solution was dialyzed through a dialysis bag (molecular weight cutoff of 7 KD) for 72 h, with the dialyzing water changed every 6 h. After dialyzing, the product was freeze-dried under vacuum to obtain oxidized dextran with a yield of 80% and an oxidation degree of 56%.

[0041] Preparation of Dendrobium-Glycyrrhizic Acid Self-Assembled Gel by Spray: Dendrobium-glycyrrhizic acid self-assembled nanoparticles (GD) and modified chitosan (CS-DA) were weighed and prepared into a CS-DA / GD mixed solution with a concentration of 10 mg / mL and a GD content of 10 mM; a 25 mg / mL ODex solution was prepared separately, and the ODex solution was quickly added to the above mixed solution at a volume ratio of 1:1. The mixture was immediately shaken and vortexed to ensure full fusion, thereby obtaining Dendrobium-glycyrrhizic acid self-assembled nanogel (GD Gel).

[0042] Example 3:

[0043] 1. In vitro cell experiments (1) The MTT assay was used to evaluate the cytotoxicity of the gel spray components.

[0044] L929 and RAW264.7 cells in the logarithmic growth phase were divided into two groups of 2.5 × 10⁶ cells per well. 4 4×10 4 Cells were evenly seeded into 96-well plates. After 12 h of culture, a series of different concentrations (1.25, 2.5, 5, 10, 20 μM) of dendrobine (Den), glycyrrhizic acid (Gly), and dendrobine-glycyrrhizic acid self-assembled particles (GD) were added and co-cultured for 24 h. 10 μL of MTT was added to each well, and after incubation in the dark for 4 h, 100 μL of DMSO was added and shaken for 30 min to dissolve the formazan, which was then measured at 490 nm.

[0045] (2) Determination of the biocompatibility of hydrogels by Live / Dead fluorescence method.

[0046] L929 and RAW264.7 cells in the logarithmic growth phase were divided into two groups of 20 × 10⁶ cells per well. 4 50×10 4 Cells were evenly seeded into 24-well plates. After 12 h of culture, 5 μM GD and dendrobium phenol-glycyrrhizic acid self-assembled gel spray (GDGel) were added and co-cultured for 24 h. The culture medium was discarded, and the plates were washed three times with PBS. 250 μL of staining solution was added to each well, and the plates were incubated in the dark for 30 min. The waste solution was discarded, the dye was washed off, and the plates were observed and photographed using a laser confocal microscope at 490 nm and 535 nm.

[0047] (3) Detection of intracellular reactive oxygen species using the reactive oxygen species fluorescent probe method.

[0048] L929 cells were evenly seeded into 24-well plates and co-cultured with different concentrations (2.5, 5, 10, 20 μM) of GD for 4 h. Then, 800 μM H2O2 was added to each well and the cells were cultured for another 2 h. The cells were washed three times with PBS, stained with the fluorescent probe DCFH-DA for 30 min, and imaged and analyzed at 488 nm using a laser confocal microscope.

[0049] Example 4: Evaluation of gel spray's effect on Escherichia coli using plate coating and counting method E. coli ) and Staphylococcus aureus ( S.aureus (It has an antibacterial effect.)

[0050] 100 μL of 15 mM Den, Gly, GD, Blank Gel and GD Gel were added to 100 μL of bacterial culture and incubated at 37℃ for 2 h. Then, 10 μL of the mixed bacterial culture was plated and incubated at 37℃ for 24 h. The antibacterial results were then photographed and recorded.

[0051] Example 5: Effects of dendrobine on a mouse model of allergic skin disease.

[0052] 1. Experimental animals: 6-week-old BALB / c mice (SPF grade) were acclimatized in an SPF-grade environment for one week.

[0053] 2. Experimental Methods (1) Modeling: After animals adapted to the environment for one week, an allergic skin disease model was replicated using the 1-chloro-2,4-dinitrobenzene (DNCB) induction method. Hair was removed from one side of the mouse's back (2×2 cm). On days 1 and 3, 200 μL of 1% DNCB solution (prepared with a 3:1 acetone-olive oil base) was applied topically to the shaved area to sensitize the mice. On days 7, 9, 11, and 13, 100 μL of 0.4% DNCB was used for challenge. Skin and behavioral changes were observed and recorded daily. Successful modeling was indicated by the presence of excessive proliferation, hyperkeratosis, erythema, scaling, edema, and scratch marks on the skin pathology. The control group only underwent hair removal treatment.

[0054] Grouping and Treatment: Mice with successful modeling were randomly divided into 5 groups (n=6-8 per group): Model group, Blank Gel group, GD Gel group, and Positive Drug Control Group (Paeonol, commercially available paeonol ointment). An additional 6-8 normally fed mice that had not undergone modeling were used as the control group. Starting from day 7 of modeling, 100 μL of the corresponding treatment drug was applied topically to the AD wounds of mice in the treatment groups daily. The Paeonol group received commercially available paeonol ointment. The Control and Model groups received only routine feeding and management. The treatment period was 9 days.

[0055] (2) Skin lesion symptom scoring: During the treatment cycle, the dermatitis symptoms on the backs of mice were scored periodically, mainly observing four indicators: erythema / hemoptysis, scratch marks / erosion, scaling / lichenification, and the degree of skin edema. The scores for the first three indicators were determined based on the proportion of skin lesion area: 0 points (no manifestation), 1 point (<10%), 2 points (10%-40%), 3 points (40%-75%), and 4 points (>75%). The scoring criteria for skin edema were: 0 points (no edema), 1 point (mild edema, close to normal), 2 points (moderate edema, darker skin color), 3 points (significant swelling, light red color), and 4 points (severe edema, significantly raised and deep red skin). The final score was the sum of the four indicators.

[0056] (3) Efficacy evaluation: After treatment, blood was collected from each mouse using the ocular blood sampling method, and the serum was separated and stored at -80℃. Mice were euthanized by cervical dislocation, and the major organs and skin tissue from the wounds were collected by dissection. The sampled tissues were fixed in 4% paraformaldehyde for 48 h, and then prepared into paraffin sections. Subsequently, hematoxylin-eosin (H&E), toluidine blue (TB), and 8-OHdG staining were performed according to the instructions of each dye and reagent, and examined under a microscope.

[0057] (4) Statistical Analysis: Statistical analysis was performed using GraphPad Prism 9.0 software. Experimental data are expressed as mean ± standard deviation (mean ± SD). A two-tailed t-test was used for comparisons between two groups. One-way ANOVA was used for multiple group analyses to assess statistical significance. P < 0.05 was considered statistically significant (compared to the control group, * P <0.05,** P <0.01, *** P <0.001, **** P <0.0001).

[0058] 4. Experimental Results: (1) Particle size analysis of GD showed that GD exhibited good stability within one week. Figure 1 A); Through microscopic morphological analysis of GD and observation of the Tyndall effect ( Figure 1 B), clearly showing that GD is a uniform and stable dispersion system; molecular dynamics simulation analysis shows that GA and Den form stable nanoclusters at 40 ns ( Figure 2 A) and indicates that the formation of GD is driven by electrostatic and hydrophobic interactions, and that GA and Den are connected through electrostatic and hydrophobic interactions as well as hydrogen bonds. Figure 2 B), ultimately self-assembled into nanoparticles; the spectral characteristics of GD, Den, and Gly were analyzed to determine ( Figure 3A), GD contains the main characteristic peaks of Den and Gly, indicating that GD is composed of Den and Gly. Spectral analysis of GD Gel reveals that this composite hydrogel is formed by the cross-linking of CS-DA and ODex via dynamic imine bonds. Figure 3 B). Material performance testing through rheological properties, adhesion, and healing ability tests ( Figure 4 (AC) indicates that the hydrogel endows GD Gel with excellent rheological adaptability, strong interfacial adhesion and efficient self-healing ability through the reversible reconstruction of the dynamic bond network.

[0059] (2) In the MTT assay for cytotoxicity, the results showed that GD and its precursors maintained high cell viability and activity after co-incubation with cells. Figure 5 (A, B) The most obvious finding is that the number of cells is not significantly reduced compared to the control group. The live / dead cell fluorescence double staining experiment uses visual laser confocal imaging to quantitatively analyze the number, ratio, and morphology of live and dead cells. Figure 5 C, D), to evaluate the biocompatibility of GD Gel. Furthermore, the ability of GD to scavenge intracellular oxidative free radicals was determined by detecting ROS using laser confocal imaging. The final experimental results ( Figure 6 This indicates that GD can effectively scavenge intracellular free radicals and alleviate oxidative stress in cells and tissues. It also exhibits low cytotoxicity and good biocompatibility.

[0060] (3) The antibacterial performance was evaluated using the plate coating counting method. Figure 7 The results showed that Gly and Den had significant antibacterial effects against E. coli and S. aureus, with GD and GD Gel showing the strongest antibacterial effects, almost completely inhibiting bacterial growth, which was superior to single components and Blank Gel.

[0061] (4) GD Gel has a significant therapeutic effect on AD. Experimental results show that the GD Gel group exhibits good wound healing and anti-inflammatory effects during the treatment period. Figure 8 It significantly reduces dermatitis scores and can improve symptoms such as erythema and edema. Figure 9 In histological analysis, H&E staining of skin tissue sections showed that GD Gel could reduce the number of inflammatory cells and decrease epidermal thickening, restoring epidermal thickness to normal levels under the action of GD Gel. Figure 10 A, B). Simultaneously, TB staining was performed on skin tissue sections, and the results showed that GD Gel significantly reduced mast cell infiltration (…). Figure 11 A, B). 8-OHdG staining revealed that GD Gel can effectively scavenge intracellular reactive oxygen species and alleviate oxidative damage to nuclear DNA. Figure 12 A、B)。

Claims

1. A method for preparing dendrobium phenol-glycyrrhizic acid self-assembled gel, characterized in that, Dendrobium-glycyrrhizic acid self-assembled nanoparticles were prepared using dendrobium phenol and licorice. The dendrobium-glycyrrhizic acid self-assembled nanoparticles were then mixed with chitosan and a crosslinking agent was added to obtain dendrobium-glycyrrhizic acid self-assembled gel.

2. The method for preparing dendrobium phenol-glycyrrhizic acid self-assembled gel according to claim 1, characterized in that, The preparation method of the dendrobium phenol-glycyrrhizic acid self-assembled nanoparticles is as follows: Dendrobium phenol and glycyrrhizic acid were dissolved in dimethyl sulfoxide, and then the mixture was added dropwise to water, stirred, dialyzed, and freeze-dried to obtain dendrobium phenol-glycyrrhizic acid self-assembled nanoparticle powder.

3. The method for preparing dendrobium phenol-glycyrrhizic acid self-assembled gel according to claim 2, characterized in that, The molar ratio of dendrobine to glycyrrhizic acid in the feed is 1:2 to 2:

1.

4. The method for preparing dendrobium phenol-glycyrrhizic acid self-assembled gel according to claim 2, characterized in that, The solid content of the dendrobium phenol-glycyrrhizic acid self-assembled gel is 5 wt% to 20 wt%.

5. The method for preparing dendrobium phenol-glycyrrhizic acid self-assembled gel according to claim 1, characterized in that, The mass ratio of the dendrobium phenol-glycyrrhizic acid self-assembled nanoparticles to the chitosan is 1:1 to 20:

1.

6. The method for preparing dendrobium phenol-glycyrrhizic acid self-assembled gel according to claim 1, characterized in that, The chitosan mentioned is a chitosan modified with catechin.

7. The method for preparing dendrobium phenol-glycyrrhizic acid self-assembled gel according to claim 6, characterized in that, The method for preparing the catechin-modified chitosan is as follows: chitosan is grafted with 3,4-dihydroxyphenylpropionic acid in the presence of a condensing agent to obtain the chitosan. The mass ratio of chitosan to grafted 3,4-dihydroxyphenylpropionic acid is 10:5 to 1:

3.

8. The method for preparing dendrobium phenol-glycyrrhizic acid self-assembled gel according to claim 1, characterized in that, The crosslinking agent is a polyaldehyde dextran, and the degree of oxidation of the polyaldehyde dextran is 40%~60%.

9. The dendrobium-glycyrrhizic acid self-assembled gel prepared by the method described in any one of claims 1 to 8.

10. A pharmaceutical composition, characterized in that, It comprises the dendrobium phenol-glycyrrhizic acid self-assembled gel as described in claim 9, and a pharmaceutically acceptable carrier or excipient.

11. The pharmaceutical composition according to claim 10, characterized in that, The pharmaceutical composition is formulated as a spray or a gel.

12. The use of the dendrobium phenol-glycyrrhizic acid self-assembled gel of claim 9 or the pharmaceutical composition of claim 10 in the preparation of a medicament for the prevention and / or treatment of allergic skin diseases.

13. The application according to claim 11, characterized in that, The allergic skin disease is selected from at least one of urticaria, eczema, contact dermatitis, atopic dermatitis, allergic purpura, and drug eruption.

Images