A berberine-glycyrrhizic acid supramolecular hydrogel prepared by molecular self-assembly and its application

Abstract

This invention discloses an oxidized berberine-glycyrrhizic acid supramolecular hydrogel prepared through molecular self-assembly and its applications, belonging to the field of pharmaceutical formulation technology. This invention induces molecular self-assembly between oxidized berberine and glycyrrhizic acid by mixing them in a specific molar ratio and heating, forming a stable oxidized berberine-glycyrrhizic acid supramolecular hydrogel. Experimental results show that the oxidized berberine-glycyrrhizic acid supramolecular hydrogel provided by this invention has excellent local delivery and sustained-release properties, as well as excellent biocompatibility and skin affinity. The oxidized berberine and glycyrrhizic acid exhibit synergistic pharmacological effects, significantly reducing dermatitis scores, improving atopic dermatitis symptoms, and downregulating inflammatory factor levels. This invention, through a simple and green preparation process, transforms the difficult-to-deliver oxidized berberine into a supramolecular hydrogel with high retention efficiency, long-lasting sustained release, excellent safety, and synergistic pharmacological activity, providing a promising new strategy for the treatment of atopic dermatitis.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, and in particular to an oxidized berberine-glycyrrhizic acid supramolecular hydrogel prepared by molecular self-assembly and its applications. Background Technology

[0002] Atopic dermatitis (AD) is a common, chronic, relapsing, inflammatory skin disease clinically characterized by intense itching, dry skin, erythema, and eczematous lesions, severely impacting patients' quality of life. Its pathogenesis is complex, involving multiple factors such as skin barrier dysfunction, immune dysregulation (especially Th2 immune hyperresponsiveness), and environmental factors.

[0003] Currently, the clinical treatment of Alzheimer's disease (AD) is mainly based on topical medications, including: (1) Topical corticosteroids: as first-line drugs, they have strong anti-inflammatory effects, but long-term use can easily lead to local side effects such as skin atrophy, telangiectasia, and hirsutism, and there is a risk of rebound after discontinuation. (2) Topical calcineurin inhibitors (such as tacrolimus and pimecrolimus): as second-line drugs, they are suitable for sensitive areas such as the face, but may cause burning and stinging sensations at the initial use, and long-term safety still needs to be monitored. (3) Others: moisturizers are the basic treatment, but their use alone is insufficient for controlling moderate to severe inflammation; systemic immunosuppressants or biological agents are used for severely ill patients, but they are expensive and have the risk of potential systemic side effects. Therefore, developing a safe, efficient, suitable for long-term topical application and capable of multi-target intervention in the pathological process of AD is an urgent clinical need.

[0004] Oxidized berberine (OBB) is an oxidized form of proberberine alkaloid, found in trace amounts in plants such as Coptis chinensis, Phellodendron chinense, Smilax china, Poppy citrinum, Mahonia fortunei, and Stephania tetrandra. Studies have shown that OBB possesses significant anti-inflammatory and immunomodulatory activities, with potential inhibitory effects on Th2-type inflammation, thus aligning with the therapeutic targets of Alzheimer's disease (AD). However, similar to proberberine drugs, OBB suffers from poor water solubility, low skin permeability, and poor oral bioavailability, severely limiting its development and application as a topical medication. Currently, there are few research reports on how to efficiently deliver OBB to skin lesions and achieve long-lasting sustained-release effects. To address the delivery problem of poorly soluble drugs, synthetic polymers or liposomes are generally used as carriers. However, these carrier systems may face challenges such as complex preparation processes, limited drug loading, or potential biocompatibility issues with the carrier materials themselves. Especially for chronic diseases like Alzheimer's disease that require long-term medication, the safety, gentleness (to avoid further irritating damaged skin), and ease of production of the formulation are crucial.

[0005] In summary, existing AD treatments have limitations in terms of safety and long-term use, while OBBs, which have clear anti-inflammatory potential, face challenges in local delivery. How to apply OBBs to the local treatment of AD in a safe, effective, and highly patient-compliant dosage form has become a pressing technical problem to be solved in this field. Summary of the Invention

[0006] The purpose of this invention is to provide an oxidized berberine-glycyrrhizic acid supramolecular hydrogel prepared by molecular self-assembly and its application, in order to solve the problems existing in the prior art. This invention, through a simple and green preparation process, prepares oxidized berberine, which is difficult to deliver, into a supramolecular hydrogel with high efficiency retention, long-lasting sustained release, excellent safety and synergistic pharmacological activity, providing a promising new strategy for the treatment of atopic dermatitis.

[0007] To achieve the above objectives, the present invention provides the following solution: This invention provides a method for preparing oxidized berberine-glycyrrhizic acid supramolecular hydrogel, comprising the following steps: Glycyrrhizic acid was prepared into a glycyrrhizic acid solution, mixed with berberine oxide, heated in a water bath, and allowed to cool to obtain the berberine oxide-glycyrrhizic acid supramolecular hydrogel. The molar ratio of berberine oxide to glycyrrhizic acid is 1:(1-2).

[0008] Furthermore, the molar ratio of berberine oxide to glycyrrhizic acid is 1:1.

[0009] Furthermore, the concentration of the glycyrrhizic acid solution is 8 mg / mL.

[0010] Furthermore, the water bath heating temperature is 60°C, and the time is 2-4 minutes.

[0011] Furthermore, the water bath heating time is 2 minutes.

[0012] The present invention also provides an oxidized berberine-glycyrrhizic acid supramolecular hydrogel obtained according to the above preparation method.

[0013] The present invention also provides the application of the above-mentioned oxidized berberine-glycyrrhizic acid supramolecular hydrogel in the preparation of medicaments for the prevention and / or treatment of atopic dermatitis.

[0014] The present invention also provides a medicament for the prevention and / or treatment of atopic dermatitis, with the above-mentioned oxidized berberine-glycyrrhizic acid supramolecular hydrogel as the active ingredient.

[0015] Furthermore, it also includes pharmaceutically acceptable excipients.

[0016] Furthermore, the dosage form of the drug is an emulsion.

[0017] The present invention discloses the following technical effects: This invention utilizes the core technique of molecular self-assembly between oxidized berberine (OBB) and glycyrrhizic acid (GA). By blending and heating OBB and GA in a specific molar ratio under mild conditions, the two are induced to spontaneously and rapidly construct a three-dimensional supramolecular network through non-covalent bonds such as hydrogen bonds and hydrophobic interactions. This achieves a synergistic technical effect of "one construction, three endowments, and one realization," thereby systematically solving the current technical problems of OBB's difficulty in local and effective delivery and the narrow safety window of existing AD therapies.

[0018] Specifically: (1) A novel, carrier-free drug delivery system with clearly defined components was successfully constructed. This invention eliminates the need for exogenous synthetic materials, utilizing OBB and GA themselves as structural units to spontaneously form a stable OBB-GA supramolecular hydrogel within minutes at 60°C. Characterization by Fourier transform infrared spectroscopy and other methods confirmed the existence of intermolecular interactions, thus creating a novel form of drug delivery that is extremely simple to prepare and inherently safe.

[0019] (2) It endows OBB with excellent local delivery and sustained-release properties. The resulting supramolecular hydrogel possesses a three-dimensional porous network structure (confirmed by SEM), capable of physically encapsulating and immobilizing hydrophobic OBB within the network. Rheological testing revealed that the gel exhibits significant shear-thinning and self-healing properties, making it easy to inject or apply, and allowing it to revert to a gel state on the skin surface for local retention. In vitro release studies further confirmed that the gel can significantly delay the release of OBB, transforming the rapid release of OBB from the active pharmaceutical ingredient into a stable sustained release lasting over 48 hours, offering the possibility of long-acting therapy.

[0020] (3) It endows the formulation with excellent biocompatibility and skin affinity. Using glycyrrhizic acid, a natural product, as the main gel matrix fundamentally ensures the good biocompatibility of the formulation. The local administration method maximizes drug concentration at the lesion site, greatly reducing the risk of systemic drug exposure and laying the foundation for long-term safe use.

[0021] (4) The anti-inflammatory pharmacological synergistic effect of OBB and GA was achieved. In a DNCB-induced mouse atopic dermatitis model, topical application of OBB-GA hydrogel showed significantly better therapeutic effects than blank gel and single-component gel. It effectively reduced dermatitis scores, alleviated epidermal hyperplasia and inflammatory cell infiltration, and downregulated serum levels of inflammatory factors such as total IgE, TNF-α, IL-1β, and IL-6. This demonstrates that this supramolecular system is not only a delivery carrier but also achieves an integrated pharmacological effect of "1+1>2" by promoting the coexistence and synergy of the two active ingredients at the site of action.

[0022] In summary, the technical advantage of this invention lies in its ability to transform an active molecule (OBB) with delivery challenges into an innovative topical drug formulation that combines efficient local retention, long-lasting sustained release, excellent safety, and synergistic pharmacological activity through a simple and green preparation process, providing a promising new strategy for the clinical treatment of atopic dermatitis. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 The figure shows the optimization results of key parameters in the preparation process of oxidized berberine-glycyrrhizic acid (OBB-GA) hydrogel; where A represents the determination of the critical gel concentration (CGC) of glycyrrhizic acid; B represents the promoting effect of oxidized berberine on the gelation of glycyrrhizic acid; C represents the screening of the self-assembly molar ratio of glycyrrhizic acid and oxidized berberine; D represents the optimization of gelation temperature and time; and E represents the refinement of the optimal heating time. Figure 2 Figure 1 shows the systematic physicochemical characterization results of oxidized berberine-glycyrrhizic acid (OBB-GA) hydrogel; where A is the UV-Vis absorption spectrum; B is the Fourier transform infrared spectrum; C is the circular dichroism spectrum; D is the amplitude scan; E is the frequency scan; F is the steady-state shear; G is the time scan; H is the self-healing test; I is the Zeta potential detection result; J is the statistical result of the Zeta potential; K is the X-ray diffraction pattern; and L is the steady-state fluorescence spectrum. Figure 3 The image shows the therapeutic effect of oxidized berberine-glycyrrhizic acid (OBB-GA) hydrogel on a mouse model of DNCB-induced atopic dermatitis (AD). In the image, A represents the dynamic evolution of macroscopic skin lesions; B represents weight change; C represents the dermatitis severity score; D represents the pruritus behavior score; E represents the serum total IgE level; F represents the TNF-α level; G represents the IL-1β level; H represents the IL-6 level; and I represents the IL-10 level. Detailed Implementation

[0025] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0026] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0027] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0028] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0029] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0030] The following detailed description, through specific embodiments and experimental data, illustrates the preparation, characterization, and anti-atopic dermatitis (AD) efficacy of the oxidized berberine-glycyrrhizic acid (OBB-GA) supramolecular hydrogel of the present invention.

[0031] Example 1: Preparation and Process Optimization of OBB-GA Supramolecular Hydrogel 1. Experimental Materials Berberine oxide (OBB, CAS No.: 549-21-3, purity ≥98%, HPLC detection); glycyrrhizic acid (GA, standard, purity ≥95%, Yuanye Biotechnology); phosphate buffer (PBS, pH 7.4, Solarbio); dimethyl sulfoxide (DMSO, chromatographic grade, Sinopharm Group).

[0032] 2. Experimental Methods 2.1 Determination of Critical Gel Concentration (CGC) of GA Accurately weigh GA powder and prepare a 10 mg / mL stock solution with PBS preheated to 60°C. Measure an appropriate amount of the stock solution and serially dilute it with preheated PBS to obtain a series of solutions with final concentrations of 3, 4, 5, 6, 7, and 8 mg / mL (total volume 2 mL). Heat and stir each solution in a 60°C water bath for 2 min, then remove and allow to cool to room temperature for 3 min. Determine gel formation using the inverted bottle method (invert the container and observe sample flow within 1 minute). Figure 1 As shown in Figure A, the results indicate that concentrations of 4 mg / mL and below result in a flowable sol; 5 mg / mL exhibits a semi-flowable state; and ≥6 mg / mL forms a stable gel that does not flow when inverted. Therefore, the CGC of GA was determined to be 5-6 mg / mL. To ensure the stability of the subsequent drug loading system, 8 mg / mL was selected as the standard working concentration.

[0033] 2.2 OBB / GA molar ratio screening like Figure 1 As shown in Figure B, oxidized berberine (OBB) promotes the gelation of GA. In a GA solution with a subgel concentration (5 mg / mL), the experimental group with added OBB successfully formed a gel, while the control group with only an equal amount of solvent (DMSO) remained a solution. This directly demonstrates that OBB molecules can effectively promote and participate in the formation of the supramolecular self-assembly network of GA.

[0034] The final GA concentration was fixed at 8 mg / mL, and the molar ratios of GA to OBB were set at 2:1, 1.5:1, 1:1, 1:1.5, and 1:2. The OBB (pre-dissolved with a small amount of DMSO) was precisely calculated and weighed, and mixed with the GA stock solution. The volume was then adjusted to 2 mL with PBS and vortexed to mix. All samples were heated in a 60°C water bath for 2 minutes, cooled, and observed. Results ( Figure 1 (C) indicates that different molar ratios have a significant impact on the formation rate, uniformity, and final macroscopic properties of the gel. When the molar ratios are 2:1, 1.5:1, and 1:1, a uniform, stable gel with good macroscopic properties can be formed relatively quickly.

[0035] 2.3 Optimization of preparation process parameters Based on the above results, a gel with a ratio of (GA: 8 mg / mL, GA:OBB = 2:1, mol / mol) was selected for optimization of heating temperature and time. Temperature gradients (60℃ and 80℃) and time gradients (1, 2, 4, and 8 minutes) were set. The gelation time, gel strength, and transparency were comprehensively evaluated. Figure 1As shown in Figures D and E, temperature and time jointly determine the efficiency and quality of gel formation (such as transparency and uniformity), and are crucial for controlling process reproducibility. Sufficient heating time is necessary to ensure complete assembly, but excessive heating may not further improve gel properties or even have negative effects. Therefore, the optimal heating time, balancing efficiency and efficacy, was determined. Based on the above results, the optimal process was determined to be heating at 60℃ for 2 minutes. The gel prepared under these conditions was labeled GA-OBB Gel and used for all subsequent characterization and efficacy experiments.

[0036] Meanwhile, GA gel (8 mg / mL) without OBB and a simple physical mixture of OBB and GA (OBB+GAMix, without heating) were prepared as key controls.

[0037] Example 2 System characterization of OBB-GA supramolecular hydrogel 1. Chemical structure characterization (FTIR) Using the KBr compression method, at 4000-500 cm -1 Scan within the range. For example... Figure 2 As shown in Figure A, the UV absorption curves of OBB, GA raw materials, and OBB-GA hydrogel are compared. The characteristic absorption peak positions or shapes of the hydrogel show significant changes, indicating that after the OBB and GA molecules form a supramolecular structure, their electronic conjugation system or intermolecular stacking mode changes, providing preliminary evidence for intermolecular interactions. Figure 2 As shown in Figure B, compared with the raw materials and physical mixtures, the infrared characteristic absorption peaks of the OBB-GA hydrogel (such as the C=O group of GA and the aromatic ring of OBB) showed significant shifts, broadening, or intensity changes, confirming that OBB and GA successfully achieved supramolecular self-assembly through non-covalent bonds such as hydrogen bonds, which is the chemical basis for the formation of the hydrogel. Figure 2 As shown in Figure C, by detecting changes in chiral signals, we can reflect the chiral amplification or conformational transitions that may occur during supramolecular assembly, providing important information for understanding the ordered stacking of molecules and the formation of higher-order structures.

[0038] In summary, compared with the spectra of OBB, GA raw materials, and the physical mixture (OBB+GA Mix), the FTIR spectrum of OBB-GA Gel exhibits characteristic changes: the C=O stretching vibration peak of the GA carboxyl group is significantly broadened and slightly shifted to a lower wavenumber, while the characteristic peak shape of the OBB aromatic ring skeleton changes. This indicates that in OBB-GA Gel, non-covalent interactions such as hydrogen bonds are formed between OBB and GA molecules, rather than a simple physical mixture, thus chemically confirming the occurrence of supramolecular self-assembly.

[0039] 2. Rheological property characterization The test was performed using a rotational rheometer. For example... Figure 2 As shown in the DH diagram, dynamic frequency scanning revealed that the elastic modulus (G') of OBB-GA Gel was significantly higher than its viscous modulus (G") across the entire test frequency range (0.1-100 rad / s), indicating typical elastic solid behavior. Furthermore, the higher G' value compared to GA Gel demonstrates that the addition of OBB enhanced the network structure. Three-step step strain testing further showed that at 1% strain, G' > G" (gel state); when the strain instantaneously increased to 500%, G' decreased sharply and fell below G" (solution state, shear thinning); when the strain recovered to 1%, both G' and G" rapidly returned to their initial values ​​within tens of seconds. This fully demonstrates that OBB-GA Gel possesses excellent shear thinning properties (i.e., injectability) and rapid self-healing ability, meeting the application requirements of topical drug delivery formulations.

[0040] 3. Characterization of colloid properties and physical structure like Figure 2 As shown in Figure IJ, the Zeta potential is used to measure the surface charge of a hydrogel dispersion. A higher negative (or positive) value indicates a strong electrostatic repulsion between particles, which is a key factor in maintaining the long-term stability of the colloidal system and preventing aggregation or sedimentation.

[0041] like Figure 2 As shown in Figure K, compared with the crystallization diffraction peaks of the raw material, the XRD pattern of the OBB-GA hydrogel exhibits a broad "bun peak," indicating that its internal structure is a long-range disordered amorphous structure. This physically confirms that it is a supramolecular network formed by dynamic non-covalent cross-linking, rather than a crystalline stack.

[0042] like Figure 2 As shown in Figure L, by comparing the fluorescence emission spectra of the raw materials and the gel, the changes in the microenvironment polarity of OBB molecules before and after gel formation, or the possible fluorescence resonance energy transfer phenomenon, can be detected, providing indirect evidence for the close packing and spatial proximity of molecules in the assembly.

[0043] Example 3: Pharmacodynamic evaluation of OBB-GA supramolecular hydrogel in treating atopic dermatitis In this embodiment, atopic dermatitis model was created using dinitrochlorobenzene (DNCB).

[0044] 1. Animal model establishment and experimental grouping SPF-grade ICR male mice (6-8 weeks old) were randomly divided into 5 groups (n=10): Normal control group (Control or Con): The back was coated with a solvent (acetone: olive oil = 4:1).

[0045] Model control group (AD): DNCB modeling + application of PBS solvent.

[0046] Positive control group (DEX): DNCB modeling + application of 0.075% dexamethasone acetate cream.

[0047] Low-dose hydrogel group (Gel-L): DNCB modeling + application of GA-OBB hydrogel (molar ratio of OBB:GA=1:2, with an OBB concentration of 1.45 mg / mL).

[0048] High-dose hydrogel group (Gel-H): DNCB modeling + application of GA-OBB hydrogel (molar ratio of OBB:GA=1:1, with an OBB concentration of 2.82 mg / mL).

[0049] Methods for inducing atopic dermatitis using DNCB: On days 1 and 2, 100 μL of 5% DNCB was applied to the shaved back skin to sensitize the mice; starting from day 7, 100 μL of 0.5% DNCB was applied every 3 days for challenge, for a total of 5 times. From day 1 after sensitization, 100 μL of the corresponding preparation was applied to the skin lesions of mice in each treatment group daily for 21 consecutive days.

[0050] 2. Pharmacodynamic evaluation results 2.1 Hydrogels significantly improved the clinical symptoms of dermatitis in AD model mice. like Figure 3 As shown in Figure A, the dorsal skin of the DNCB-induced model control mice (AD) exhibited progressively worsening typical skin lesions after modeling, including erythema, edema, crusting, scaling, and epidermal peeling. Compared with the normal control group, the skin lesions in the model control mice appeared from day 4 and gradually worsened, reaching a peak between days 10 and 13, subsequently entering a chronic inflammatory stage, manifested as skin thickening and lichenification. Treatment with the positive control drug dexamethasone (DEX) and different doses of GA-OBB hydrogel (Gel-L, Gel-H) significantly improved the aforementioned skin lesions and dermatitis. Among them, the high-dose hydrogel group (Gel-H) showed the most significant improvement, with the skin lesion recovery speed and appearance similar to the DEX group; although the improvement effect of the low-dose hydrogel group (Gel-L) was weaker than that of the Gel-H group, it was still significantly better than that of the model control group, indicating that GA-OBB hydrogel can reduce skin damage in a dose-dependent manner.

[0051] 2.2 Hydrogels effectively reduce dermatitis scores and alleviate itching. like Figure 3 As shown in Figure C, the dynamic dermatitis scoring results showed that the model control group (AD) score increased significantly over time, reaching its peak on day 13. In contrast, the Gel-H group had a significantly lower score than the model group from day 4, and the score dropped to about 1 point by day 19, with an effect similar to the positive control group (DEX); the Gel-L group showed the second largest decrease in score.

[0052] like Figure 3 As shown in Figure D, regarding scratching behavior, the scratching time in the model control group remained high from day 8 onwards. The Gel-H group experienced significant relief from itching, with scratching time significantly lower than the model control group from day 8, and the effect was comparable to the DEX group by day 20. The Gel-L group showed the second-best antipruritic effect, exhibiting a dose-dependent effect. This indicates that the hydrogel provided by this invention can effectively relieve the clinical symptoms and itching of Alzheimer's disease (AD).

[0053] 2.3 The hydrogel did not significantly inhibit the body weight of the model mice, and its safety profile was good. like Figure 3 As shown in Figure B, throughout the experiment, except for the positive control group (DEX), the body weight of mice in all other groups showed a steady increase. The body weight of mice in the positive control group decreased significantly from day 6 after administration, indicating that long-term topical application of DEX has a significant inhibitory effect on growth, which is a systemic side effect of glucocorticoids. In contrast, the body weight of mice in the low- and high-dose hydrogel groups (Gel-L and Gel-H) increased steadily, with a trend basically consistent with the AD model group, and no significant difference from the model group at the experimental endpoint. This indicates that the GA-OBB hydrogel provided by this invention, while exerting its therapeutic effect, did not exhibit the same weight-inhibiting side effect as DEX, suggesting good local application safety.

[0054] 2.4 Hydrogel systems regulate serum immune and inflammatory factor levels like Figure 3 As shown in the EI results, serum immunological tests revealed that, compared with the normal control group, the serum levels of total IgE and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the model control group (AD) mice were significantly increased, while the level of the anti-inflammatory cytokine IL-10 was significantly decreased. This imbalance was significantly improved after hydrogel treatment. Compared with the model control group, the Gel-H group most effectively reduced serum IgE, TNF-α, IL-1β, and IL-6 levels, with effects comparable to the DEX group, and significantly increased IL-10 levels; the improvement in each indicator in the Gel-L group was weaker than that in the Gel-H group, showing a dose-dependent effect.

[0055] The results showed that GA-OBB hydrogel could systematically inhibit systemic allergic and inflammatory responses in AD model mice by downregulating pro-inflammatory mediators and upregulating anti-inflammatory factors.

[0056] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for preparing an oxidized berberine-glycyrrhizic acid supramolecular hydrogel, characterized in that, Includes the following steps: Glycyrrhizic acid was prepared into a glycyrrhizic acid solution, mixed with berberine oxide, heated in a water bath, and allowed to cool to obtain the berberine oxide-glycyrrhizic acid supramolecular hydrogel. The molar ratio of berberine oxide to glycyrrhizic acid is 1:(1-2).

2. The preparation method according to claim 1, characterized in that, The molar ratio of berberine oxide to glycyrrhizic acid is 1:

1.

3. The preparation method according to claim 1, characterized in that, The concentration of the glycyrrhizic acid solution was 8 mg / mL.

4. The preparation method according to claim 1, characterized in that, The water bath heating temperature is 60℃, and the time is 2-4 minutes.

5. The preparation method according to claim 4, characterized in that, The water bath heating time is 2 minutes.

6. An oxidized berberine-glycyrrhizic acid supramolecular hydrogel obtained by the preparation method according to any one of claims 1-5.

7. The use of the oxidized berberine-glycyrrhizic acid supramolecular hydrogel of claim 6 in the preparation of a medicament for the prevention and / or treatment of atopic dermatitis.

8. A drug for the prevention and / or treatment of atopic dermatitis, characterized in that, The active ingredient is the oxidized berberine-glycyrrhizic acid supramolecular hydrogel as described in claim 6.

9. The medicament as described in claim 8, characterized in that, It also includes pharmaceutically acceptable excipients.

10. The medicament as claimed in claim 8, characterized in that, The drug is in the form of an emulsion or a gel.

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