Preparation method of traditional Chinese medicine hydrogel for treating psoriasis

Abstract

The invention provides a preparation method of traditional Chinese medicine hydrogel for treating psoriasis, the hydrogel preparation is prepared from the following raw material medicines in parts by weight: 20-40 parts of PVA, 60-80 parts of borax, 20-40 parts of glycyrrhizic acid, 8-12 parts of paeoniflorin and 2-3 parts of glycerin, the hydrogel has the advantages of injectability, self-healing, stretchability and the like, can meet the requirements of skin dressing, can be tightly attached to the skin, and has a good application prospect. The separation is easy. Animal experiments prove that after being loaded with paeoniflorin, the gel has the curative effect of treating mild and moderate psoriasis, the treatment effect is remarkable, and the gel has a wide market application prospect.

Description

Technical Field

[0001] This invention relates to a method for preparing a traditional Chinese medicine hydrogel for treating psoriasis, belonging to the field of biomedical materials. Background Technology

[0002] Hydrogels, with their hydrophilic three-dimensional network structure, have become a promising drug carrier material due to their high porosity, excellent water retention capacity, and good biocompatibility. Gel-based drug therapy is an emerging local drug delivery strategy. This technology utilizes the three-dimensional polymer network of hydrogels as a "reservoir" to load and control the release of drugs. Based on these characteristics, gel formulations can achieve intelligent drug delivery: not only can they effectively enhance drug permeability in the thickened stratum corneum and retention time at the lesion site, achieving long-acting sustained release and thus reducing the frequency of medication; they can also respond to the skin lesion microenvironment (such as pH, enzyme activity) or external stimuli (such as light, heat), achieving precise on-demand drug delivery. This can significantly reduce the side effects such as skin irritation and atrophy commonly found in traditional topical medications while improving efficacy. In addition, gel formulations have the advantage of good moisturizing properties and overcome the disadvantage of traditional topical preparations that easily stain clothing. Although existing hydrogel systems have made significant progress, they still have significant shortcomings in terms of mechanical properties and environmental stability. To overcome these limitations, researchers have developed dual-network hydrogels. The unique properties of dual-network hydrogels stem from their ingenious structural design. This system typically consists of two polymer networks with different properties: the first network is a rigid, brittle sacrificial network, often formed from polyelectrolytes or rigid-chain polymers, whose main function is to disperse and dissipate external forces through fracture; the second network is composed of flexible polymers, responsible for maintaining the overall softness and elasticity of the material. Under external force, the first network fractures first, effectively dissipating energy and protecting the second network from damage, thus giving the hydrogel excellent strength and toughness on a macroscopic scale. This "sacrificial bond" mechanism is the core principle behind the enhancement achieved by dual-network hydrogels. Furthermore, by introducing dynamic physical interactions such as nanocomposites, topological entanglement, hydrogen bonding, or ion coordination to construct physically cross-linked networks, their properties can be further optimized. Dual-network hydrogels not only significantly improve mechanical strength and toughness but also expand the diversity of functional designs, successfully overcoming the limitations of traditional hydrogels in terms of mechanical properties. Due to their excellent structural tunability and performance advantages, this type of hydrogel has become a promising new drug carrier formulation for topical treatment of psoriasis.

[0003] A search revealed that similar technical literature to the hydrogel system of this invention includes: Patent CN120242132A discloses a chlorogenic acid-based dual-network hydrogel, its preparation method, and its applications. The first network of this hydrogel consists of CA and Zn. 2+The second network, formed by heparin-grafted gelatin and covalently cross-linked with genipin, enhances mechanical strength, prolongs drug release time at the wound site, accelerates chronic wound healing, and prevents scar formation. Patent CN120983707A reports the preparation and application of a dual-network hydrogel. The first layer of the spinal cord decellularized matrix (dSECM) self-assembles to form the first layer of the spinal cord decellularized matrix network (DSM), while the second layer, a metal-polyphenol network (MPN), is formed by the coordination of metal ions and polyphenols. This hydrogel can regulate the immune response in the spinal cord microenvironment after spinal cord injury (SCI), inhibit inflammation and the accumulation of reactive oxygen species (ROS), and provide favorable conditions for nerve regeneration and tissue repair. Patent CN120860325A discloses a sustained-release exosome hydrogel scaffold for repairing diabetic bone defects and its preparation method. It utilizes DSPE-PEG- Biotin (Amphiphilic phospholipid molecules) are inserted into the exosome lipid bilayer to achieve efficient biotinylation. The hydrogel of this invention has a dual-network structure: oxidative... Puju sugar The aldehyde group forms a first-layer network with the amino group of QCS-MA through dynamic Schiff base bonds, and the methacrylate of QCS-MA forms a second-layer network through photopolymerization. This hydrogel exhibits long-lasting sustained release and mechanical compatibility. In addition, Liu Xinyue et al. reported the preparation and drug sustained-release application of saponin-based hydrogels (Preparation and Drug Sustained-Release Application of Saponin-Based Hydrogels. Biomass Chemical Engineering, 2025). The study showed that the saponin-based hydrogel prepared after oxidation treatment exhibited increased elongation at break and tensile strength, while maintaining the integrity of the internal cross-linked network structure. Release kinetics experiments showed that the cumulative release rate of the saponin-based hydrogel was as high as 50%.

[0004] Xiong Fangjiao et al. reported the preparation and properties of recombinant collagen hydrogels with wound-healing function (Preparation and Properties of Recombinant Collagen Wound-Healing Hydrogels. Materials Engineering, 2025, https: / / link.cnki.net / urlid / 11.1800.TB.20251121.1252.002). This paper describes the preparation of multi-network structured multifunctional hydrogels using recombinant collagen, tannic acid, methacrylamide, and acrylic acid as raw materials via in-situ polymerization. This gelling agent effectively improves the mechanical properties of the hydrogel, exhibits good antibacterial effects, and low cytotoxicity.

[0005] Based on the above review of relevant patents and literature, it is evident that dual-network or multi-network hydrogel systems can effectively enhance the mechanical strength of materials and achieve long-term sustained drug release, providing strong support for biomedical applications. However, many natural drug components with good bioactivity (such as paeoniflorin), despite possessing anti-inflammatory, antioxidant, and immunomodulatory functions, suffer from drawbacks such as weak mechanical properties, poor water solubility, and rapid in vivo metabolism, making it difficult to maintain effective therapeutic concentrations and necessary physical support at the lesion site. Therefore, loading these components into suitable hydrogel carriers, and achieving mechanical enhancement, stable encapsulation, and controlled release through carrier structure, is a key strategy to overcome the bottleneck in their clinical translation. Summary of the Invention

[0006] This invention provides a method for preparing a traditional Chinese medicine hydrogel for treating psoriasis. The hydrogel preparation exhibits excellent mechanical properties, including high tensile strength, good fracture toughness, and rapid self-healing ability.

[0007] More importantly, the active ingredients selected in this invention are paeoniflorin and glycyrrhizic acid, which can synergistically interact with the gel network. Furthermore, through intermolecular hydrogen bonds, the cross-linking density and dynamic interactions within the system can be further enhanced, thereby significantly improving the flexibility, viscoelasticity, and structural stability of the hydrogel.

[0008] This enhanced network structure provides an ideal and stable carrier environment for drug encapsulation and sustained, controlled release. This herbal hydrogel formulation also possesses advantages such as injectability, self-healing, and stretchability, meeting the requirements for skin dressings. It adheres tightly to the skin and is easily detached. Animal experiments have verified that the gel loaded with paeoniflorin has therapeutic efficacy in treating mild to moderate psoriasis, with therapeutic effects comparable to positive control drugs. Furthermore, the preparation cost of this invention's gel is more than 50% lower than that of commercially available drugs.

[0009] This invention designs a stretchable, self-healing dual-network herbal hydrogel. The first network is formed by crosslinking PVA and borax. PVA, as a water-soluble polymer, is rich in hydroxyl groups in its molecular chain, which can form dynamically reversible borate ester bonds with borax, endowing the gel with excellent self-healing properties and effectively dissipating external forces. The second network is constructed through multiple hydrogen bond interactions between glycyrrhizic acid-glycyrrhizic acid, glycyrrhizic acid-PVA, and PVA-PVA, significantly enhancing the gel's flexibility and viscoelasticity. This dynamic dual-network structure significantly improves the hydrogel's mechanical properties, giving it high tensile strength, excellent fracture toughness, and rapid self-healing ability, while also meeting the requirements for injectability, stretchability, and good adhesion as a skin dressing.

[0010] The technical solution of this invention patent application is as follows:

[0011] A hydrogel preparation of traditional Chinese medicine, characterized in that the hydrogel preparation is made from the following raw materials in the following weight ratio: 20-40 parts of PVA (polyvinyl alcohol), 60-80 parts of borax, 20-40 parts of glycyrrhizic acid, 8-12 parts of paeoniflorin, and 2-3 parts of glycerin.

[0012] Preferably, the herbal hydrogel preparation is made from the following raw materials in the indicated weight ratios: 30 parts PVA (polyvinyl alcohol), 70 parts borax, 30 parts glycyrrhizic acid, 10 parts paeoniflorin, and 2.5 parts glycerin.

[0013] Preferably, the method for preparing the traditional Chinese medicine hydrogel includes the following steps:

[0014] (1) Weigh glycyrrhizic acid, add glycerol aqueous solution, heat at 50~70℃, stir for 7~12 minutes to mix thoroughly, then remove and let stand at room temperature to cool, to obtain glycyrrhizic acid hydrogel;

[0015] (2) Mix polyvinyl alcohol, glycyrrhizic acid, paeoniflorin and glycerol aqueous solution thoroughly, and heat and stir at 75~85℃ for 8~12 minutes to obtain a mixed solution;

[0016] (3) Alternatively, borax is dissolved in an aqueous glycerol solution, heated at 50-70°C and stirred until completely dissolved to obtain a borax solution;

[0017] (4) Take the borax solution from step (3) while it is still hot and quickly add it dropwise to the mixed solution from step (2) while it is being stirred. After about 15 seconds, gel formation can be observed.

[0018] Preferably, in step (1) of the preparation method, the heating temperature is 60°C and the stirring time is 10 minutes.

[0019] Preferably, in step (2) of the preparation method, the heating temperature is 80°C and the stirring time is 10 minutes.

[0020] Preferably, the heating temperature in step (3) of the preparation method is 60°C.

[0021] The application of the aforementioned traditional Chinese medicine hydrogel preparation in the preparation of drugs for treating psoriasis.

[0022] To obtain a scientific and reasonable process route for preparing the hydrogel drug of this invention, extensive preliminary research was conducted. The following is a summary of some experimentally explored and optimized process steps:

[0023] 1.1 Gel composition: PVA, borax, glycyrrhizic acid, distilled water. Glycerin.

[0024] Table 1. Drug composition of the herbal hydrogel

[0025] Components Concentration ratio PVA 30 mg / mL Borax 70 mg / mL glycyrrhizic acid 30 mg / mL glycerin 2% v / v

[0026] 1.2 Method for preparing traditional Chinese medicine hydrogels in this invention:

[0027] The specific steps for gel preparation are as follows:

[0028] Weigh 60 mg of glycyrrhizic acid and transfer it to a glass vial. Then add 2 mL of glycerol aqueous solution, heat and stir at 60 °C for 10 minutes to mix thoroughly, then remove and let stand at room temperature to cool to obtain glycyrrhizic acid hydrogel.

[0029] Mix 60 mg of polyvinyl alcohol, 60 mg of glycyrrhizic acid, and 1 mL of glycerol aqueous solution in a small glass bottle. Heat and stir at 80 °C for 10 minutes to obtain a mixed solution. Separately, dissolve 140 mg of borax in 1 mL of glycerol aqueous solution. Heat and stir at 60 °C until completely dissolved to obtain a borax solution. Then, rapidly add the hot borax solution dropwise to the stirred mixed solution. Gel formation can be observed after about 15 seconds.

[0030] Gel preparation process parameter screening and optimization process:

[0031] Glycyrrhizic acid is one of the important active ingredients in licorice. Under certain conditions, it spontaneously forms a gel, making it one of the few small-molecule gelling agents among natural products. To determine its gel-forming concentration, we first evaluated the gel-forming concentration of glycyrrhizic acid (GA) using the inverted plate method.

[0032] Experimental results showed that a gel could be formed when the glycyrrhizic acid concentration reached 10 mg / mL. Subsequently, its rheological behavior was further investigated using frequency sweep spectroscopy. At concentrations of 10 mg / mL and 20 mg / mL, the storage modulus (G′) and loss modulus (G″) alternately led with increasing frequency, indicating an unstable gel structure and poor mechanical properties. However, when the glycyrrhizic acid concentration increased to 30 mg / mL and above, G′ and G″ remained relatively stable within the tested frequency range, with G′ consistently higher than G″, indicating the formation of a stable, continuous three-dimensional network structure. Experimental results can be found in the appendix to the instruction manual. Figure 1 While increasing the concentration helps enhance the mechanical strength of the gel, excessively high GA concentrations can lead to an overly hard gel and may pose a risk of skin irritation, such as stinging sensations in sensitive skin or dehydration of the stratum corneum. Therefore, considering both gel performance and biosafety, the GA concentration was determined to be 30 mg / mL in subsequent experiments.

[0033] A stable borate ester-bonded gel was formed at a PVA concentration of 30 mg / mL and a borax concentration of 50 mg / mL. Based on this, the PVA concentration was kept constant at 30 mg / mL, and the borax concentration was increased to investigate its effect on gel properties. Rheological tests were performed on the resulting gels, and the results are shown in the figure. When the borax concentration was increased to 70 mg / mL, the gel exhibited optimal mechanical properties. The experimental results can be found in the appendix to the instruction manual. Figure 2 .

[0034] However, further increasing the borax concentration led to a decrease in performance. This is presumably because excessively high crosslinking density resulted in an overly dense and brittle gel network structure, or caused localized over-crosslinking, forming an uneven structure and thus weakening its overall mechanical properties. Therefore, considering the above results, subsequent experiments selected a PVA concentration of 30 mg / mL and a borax concentration of 70 mg / mL as the optimized formulation conditions. To further enhance the application potential of this gel system in drug delivery, we introduced 2% glycerol into the aqueous phase to enhance the transdermal absorption performance of the drug. Based on the above gel formulation screening, we prepared a PVA-borax-glycyrrhizic acid hydrogel, which was yellow in color.

[0035] 1.3 Study on the mechanical properties of the herbal hydrogel of this invention

[0036] Hydrogels, as drug delivery materials, must undergo mechanical property evaluation before use. Rheology, the science that studies the flow and deformation of matter, is one of the most crucial and effective characterization methods for viscoelastic materials like gels, which possess both solid and liquid properties. We first used oscillation amplitude scanning to test the linear viscoelastic region of the gels, and several gels remained stable at strain amplitudes below 10%. Through frequency scanning tests in rheology, we confirmed the successful formation of each gel system.

[0037] The results showed that the 30 mg / mL glycyrrhizic acid hydrogel exhibited typical solid-like behavior across the entire frequency range, with its storage modulus (G′) consistently higher than its loss modulus (G″), indicating the formation of a stable three-dimensional network structure. In contrast, the gel containing borate ester bonds exhibited a significant frequency-dependent transition: in the low-frequency region, G′ < G″, exhibiting liquid-like behavior; while when the frequency increased to approximately 1 Hz or higher, G′ > G″, and the material transitioned to a solid-like response. This behavior stems from the dynamic reversible nature of borate ester bonds. Under low-frequency conditions, the deformation timescale is relatively long, allowing sufficient time for the borate ester bonds to break and recombine. The broken bonds may not necessarily recover in situ but may form new bonds with adjacent chain segments. This continuous “break-recombination” process causes the polymer network to undergo macroscopic recombination and flow, with energy mainly dissipated as heat through chain slip (G″ being dominant), thus the material exhibits viscous liquid characteristics. However, under high-frequency conditions, the deformation timescale is extremely short, and external oscillations change rapidly, preventing the borate ester bonds from completing a full “break-recombination” cycle. When the cross-linked network is not relaxed in time, it is "frozen," exhibiting a temporarily stable elastic structure. At this point, the polymer chains are anchored by the cross-linking points, primarily undergoing elastic deformation, and energy is effectively stored (G′ dominates), thus the material exhibits solid-like mechanical behavior. Furthermore, we observed that G″ of the borate ester bond gel exhibits a non-monotonic change with increasing frequency, first decreasing and then increasing, reflecting the dynamic transformation of its internal dissipation mechanism. In the initial decreasing phase, as the frequency approaches the characteristic relaxation time of the borate ester bond, the dissociation and recombination of dynamic bonds cannot keep up with the external deformation rate; some bonds "cannot respond in time" within the deformation cycle, exhibiting elastic cross-linking point-like behavior, thereby reducing viscous dissipation. Subsequently, when the frequency exceeds a certain critical value, G″ increases again. Experimental results can be found in the appendix of the instruction manual. Figure 3 This is attributed to the fact that under extremely high frequency driving, the rapid motion of polymer chain segments and solvent molecules becomes dominant, and their inherent internal friction and inertial resistance increase significantly, leading to a sharp increase in viscous dissipation based on physical friction.

[0038] To verify the formation of hydrogen bonds and reversible borate ester bonds, we performed infrared spectroscopy analysis on each gel sample. The results showed that the absorption peak at 1340 cm⁻¹ was attributed to the B–O stretching vibration, a characteristic peak of borate ester bonds. The B–C (aromatic ring) stretching vibration near 1100 cm⁻¹ and the B–O–C bending vibration at 660 cm⁻¹ further confirmed the successful formation of reversible borate ester bonds in all three gels. Furthermore, compared to the PVA-borax gel, the O–H stretching vibration peak in the 3400–3200 cm⁻¹ range of the PVA-borax-glycyrrhizic acid hydrogel was significantly broadened. Experimental results can be found in the appendix to the instruction manual. Figure 4 This indicates that the introduction of glycyrrhizic acid and paeoniflorin enhances the hydrogen bond interactions within the system.

[0039] The crystal structure of the sample was further analyzed by X-ray diffraction (XRD). (See attached instruction manual.) Figure 5 As shown, pure PVA exhibits a sharp diffraction peak near 19.5°, a typical characteristic of its semi-crystalline structure; while glycyrrhizic acid and paeoniflorin show broadened diffuse peaks in this region, indicating that both are amorphous. After the formation of PVA-borax-glycyrrhizic acid hydrogel, the intensity of the characteristic peak at 19.5° significantly decreases, indicating that the crystallinity of PVA is significantly reduced due to the formation of the gel network.

[0040] 11 The B NMR spectrum results are shown in the attached instruction manual. Figure 6 As shown, the different chemical forms of boron in the gel system were clearly identified. The signal at 1 ppm belongs to the borate anion [B(OH)4]⁻, which is the most significant characteristic peak of borax. The signals appearing at 9.78 and 9.82 ppm correspond to the less stable open-chain borate ester structures. The resonance peaks at 13.03 and 13.66 ppm originate from the three-coordinate borate ester bond (B–O–C), which is the main cross-linking structure constituting the three-dimensional network of the gel.

[0041] To verify whether the dual-network hydrogel prepared after introducing additional components still possesses the injectability and self-healing ability conferred by reversible borate ester bonds, we conducted rheological tests and syringe injection experiments. First, the injectability of the material was evaluated through steady-state shear tests. (See attached instructions.) Figure 7 As shown, all gels exhibited typical shear-thinning behavior, with viscosity decreasing as the shear rate increased, indicating the formation of a dynamic network structure. Injection experiments further confirmed that the herbal hydrogels prepared in this invention possess excellent injectability. The gels could be smoothly extruded using a syringe, and recovered to a complete block shape after 30 seconds of injection; furthermore, the gels could even be extruded through a fine-aperture needle, continuously writing a complete “TUTCM” letter pattern.

[0042] The thixotropic recovery behavior and self-healing properties of the gel were further investigated using step strain tests under oscillation time-scanning. Results are shown in the appendix to the instruction manual. Figure 8 As shown, under low strain (linear viscoelastic region), all gels exhibit solid-like behavior (G′ > G″); when switching to high strain, G′ drops sharply and falls below G″, and the material changes from solid-like behavior to liquid-like behavior. After the strain recovers to a lower level, the G′ of the GA gel can only recover to about 30% of its initial value, while the G′ of the other gels containing borate ester bonds can basically recover to the initial level, indicating that their internal dynamic bonds can quickly recombine, achieving network structure reconstruction. This recovery behavior can be maintained after multiple cycles, proving that this type of gel has excellent and stable self-healing ability.

[0043] We cut the entire gel in half lengthwise with a scalpel blade, then brought the cut surfaces into close contact. The experimental results can be found in the instruction manual. Figure 9-10 The results showed that the gel containing borate ester bonds could reheal into a complete block within 10 seconds after being cut, further demonstrating its excellent self-healing properties.

[0044] To further characterize the practical properties of the hydrogel, we evaluated its adhesive and tensile properties. Adhesion tests showed that the gel adheres firmly to various material surfaces, including glass, plastic, and metal, and does not detach even when inverted, demonstrating excellent universal adhesive ability. Simultaneously, when applied to human finger skin, the gel can withstand finger bending without falling off and can be easily peeled off without residue. Experimental results can be found in the instruction manual. Figure 11 The mechanical tensile test further revealed the performance differences between the different components, as shown in the attached instruction manual. Figure 12 As shown, the elongation at break of PB gel is about 400%, while the elongation at break of PBG gel and PBG@PF gel formed by introducing GA and PF are significantly increased to about 1000%, indicating that the dual network structure effectively enhances the ductility and flexibility of the material.

[0045] The experimental results above demonstrate that this study successfully constructed and systematically characterized a composite gel system based on glycyrrhizic acid (GA) and polyvinyl alcohol (PVA)-borax. Stable and reversible boronic acid ester bonds and strong hydrogen bond interactions were formed in this system. This research lays an important theoretical and experimental foundation for developing structurally controllable and high-performance natural small molecule gel carriers.

[0046] Beneficial effects of the herbal hydrogel formulation of this invention

[0047] (1) This invention proposes a novel hydrogel system comprising glycyrrhizic acid, polyvinyl alcohol (PVA), and borax as a composite gel carrier for traditional Chinese medicine, and loaded with paeoniflorin. PVA, as a water-soluble polymer, has abundant hydroxyl groups that can form dynamically reversible borate ester bonds with borax, constructing a cross-linked network with self-healing properties. Glycyrrhizic acid not only possesses anti-inflammatory and immunomodulatory activities, but its amphiphilic structure can self-assemble into a gel network, further interacting with PVA through hydrogen bonds and hydrophobic interactions to enhance network stability and drug loading capacity. This carrier system can effectively encapsulate paeoniflorin, improving its solubility and stability while achieving sustained drug release and mechanical property adaptation through a tunable dynamic cross-linked network, providing a new approach for the development of hydrogel formulations that combine mechanical support and long-lasting efficacy.

[0048] After extensive experimental optimization, the optimal hydrogel formulation ratio of this invention is: 30 parts PVA (polyvinyl alcohol), 70 parts borax, 30 parts glycyrrhizic acid, 10 parts paeoniflorin, and 2.5 parts glycerol. Glycyrrhizic acid was chosen as the pharmaceutical raw material because it spontaneously forms a gel under certain conditions. The concentration of glycyrrhizic acid was determined to be 30 mg / mL using the inverted plate method, resulting in a stable, continuous three-dimensional network structure. This invention introduces 2% glycerol into the aqueous phase to enhance the transdermal absorption performance of the drug. Furthermore, the addition of paeoniflorin enhances the stability of the herbal hydrogel formulation by increasing the hydrogen bond interaction between glycyrrhizic acid and paeoniflorin within the system.

[0049] (2) Through rheological testing and syringe injection experiments, the herbal hydrogels of this invention all exhibited typical shear-thinning behavior; the viscosity of the gel decreased with increasing shear rate, indicating the formation of a dynamic network structure. Injection experiments confirmed that the hydrogels of this invention all possess good injectability. The gel could be smoothly extruded using a syringe, and after 30 seconds of injection, the gel could recover to a complete block shape. When the complete gel was cut in half with a scalpel blade, and the cut surfaces were then brought into close contact, the gel containing borate ester bonds could heal back to a complete block within 10 seconds after being cut, demonstrating the good self-healing properties of the gels of this invention.

[0050] Hydrogel adhesion tests showed that the gel could firmly adhere to the surfaces of various materials such as glass, plastic, and metal, and would not detach even when inverted, demonstrating excellent universal adhesion ability. In particular, its elongation at break was significantly increased to approximately 1000%, indicating that the dual-network structure effectively enhanced the material's ductility and flexibility. The paeoniflorin-glycyrrhizic acid composite herbal hydrogel prepared in this invention has advantages such as injectability, self-healing, and stretchability, meeting the requirements for skin dressings, adhering closely to the skin, and easily detaching.

[0051] (3) Animal experiments verified that all gel treatment groups and positive drug groups showed inhibition of skin lesion progression. Among them, the glycyrrhizic acid-paeoniflorin compound hydrogel of the present invention (PF10@PBG group) showed the most significant improvement effect, while the other groups also showed varying degrees of relief, as evidenced by a slower increase in PASI scores. At the end of treatment, the average PASI score of the PF10@PBG group was significantly lower than that of the model group; the scores of the other treatment groups were also lower than those of the model group. The above results fully demonstrate that the topical application of the glycyrrhizic acid-paeoniflorin compound traditional Chinese medicine gel of the present invention can effectively reduce the severity of IMQ-induced psoriasis in mice.

[0052] The glycyrrhizic acid-paeoniflorin drug compound preparation hydrogel group of the present invention showed an increasing trend in body weight on the third day, while the body weight increase time of mice in other groups was delayed, suggesting that the gel preparation may have a positive regulatory effect on metabolic state while alleviating systemic inflammation.

[0053] In contrast, both the positive control group and the treatment group treated with the glycyrrhizic acid-paeoniflorin compound hydrogel of the present invention (PF10@PBG group) showed significant pathological improvements, including reduced epidermal thickness, alleviated keratinization abnormalities, and decreased inflammatory cell infiltration. Among all treatment groups, the glycyrrhizic acid-paeoniflorin compound hydrogel group of the present invention showed the most significant improvement, with the best restoration of epidermal structure and granular layer continuity, and its tissue morphology being closest to normal skin.

[0054] In summary, the herbal hydrogel of this invention, loaded with paeoniflorin, is effective in treating mild to moderate psoriasis, and its therapeutic effect is comparable to that of positive control drugs. Furthermore, the preparation cost of the gel of this invention is more than 50% lower than that of commercially available drugs.

[0055] Instruction manual illustrations

[0056] The accompanying drawings are provided to further explain the herbal hydrogel formulation of the present invention and constitute a part of the present invention. The illustrative embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention.

[0057] Appendix Figure 1 The effects of different frequencies and glycyrrhizic acid concentrations on storage modulus (G′) and loss modulus (G″);

[0058] Appendix Figure 2 The effects of different frequencies and PVA (polyvinyl alcohol) and borax concentrations on storage modulus (G′) and loss modulus (G″);

[0059] Appendix Figure 3 Storage modulus (G′) and loss modulus (G″) of glycyrrhizic acid gel, PVA-borax gel, PVA-borax-glycyrrhizic acid gel and PVA-borax-glycyrrhizic acid gel loaded with paeoniflorin.

[0060] Appendix Figure 4 Infrared spectra of PVA, glycyrrhizic acid, paeoniflorin, PVA-borax-glycyrrhizic acid gel, and PVA-borax-glycyrrhizic acid gel loaded with paeoniflorin;

[0061] Appendix Figure 5 XRD patterns of PVA, glycyrrhizic acid, paeoniflorin, PVA-borax-glycyrrhizic acid gel, and PVA-borax-glycyrrhizic acid gel loaded with paeoniflorin;

[0062] Appendix Figure 6 11B-NMR spectra of borax, PVA-borax-glycyrrhizic acid gel and PVA-borax-glycyrrhizic acid gel loaded with paeoniflorin;

[0063] Appendix Figure 7Viscosity-shear rate test and injectability test of PVA-borax gel, PVA-borax-glycyrrhizic acid gel and PVA-borax-glycyrrhizic acid gel loaded with paeoniflorin.

[0064] Appendix Figure 8 Continuous step strain test of glycyrrhizic acid gel, PVA-borax gel, PVA-borax-glycyrrhizic acid gel and PVA-borax-glycyrrhizic acid gel loaded with paeoniflorin;

[0065] Appendix Figure 9 Injection healing test of PVA-borax-glycyrrhizic acid gel loaded with paeoniflorin;

[0066] Appendix Figure 10 Self-healing test of PVA-borax-glycyrrhizic acid gel loaded with paeoniflorin;

[0067] Appendix Figure 11 Adhesion test of PVA-borax-glycyrrhizic acid gel loaded with paeoniflorin on different material surfaces;

[0068] Appendix Figure 12 Tensile tests of PVA-borax gel, PVA-borax-glycyrrhizic acid gel and PVA-borax-glycyrrhizic acid gel loaded with paeoniflorin;

[0069] Appendix Figure 13 Different drugs affect the psoriasis area and severity index scores during the psoriasis modeling experiment;

[0070] Figure 14 Changes in body weight of mice in different groups during the psoriasis modeling experiment;

[0071] Figure 15 Skin surface changes and section staining experiments of mice in different groups during the psoriasis modeling experiment;

[0072] Figure 16 The number of CD3+ cells, CD4+ cells, CD8+ cells and TH17 cells in different groups of mice after the psoriasis modeling experiment. Detailed Implementation

[0073] To better understand the implementation of this invention, one or more experimental examples are listed below. The invention will be further illustrated by typical embodiments. In this invention, PVA represents polyvinyl alcohol, IMQ is imiquimod cream, which is a mouse psoriasis modeling drug; PF10@PBG gel is a hydrogel of the glycyrrhizic acid-paeoniflorin drug composite preparation of this invention, obtained by reacting PVA-borax with glycyrrhizic acid and loading paeoniflorin.

[0074] Example 1

[0075] (1) Weigh 30mg of glycyrrhizic acid, add it to a glycerol aqueous solution, heat at 60℃ and stir for 10 minutes to mix thoroughly, then remove it and let it cool at room temperature to obtain glycyrrhizic acid hydrogel;

[0076] (2) Place 60 mg of polyvinyl alcohol, 30 mg of glycyrrhizic acid and 1 mL of glycerol aqueous solution in a small glass bottle and mix thoroughly. Heat and stir at 80 °C for 10 minutes to obtain a mixed solution.

[0077] (3) Separately weigh 140 mg of borax and dissolve it in 1 mL of glycerol aqueous solution. Heat the solution at 60 °C and stir until completely dissolved to obtain a borax solution.

[0078] (4) Take the borax solution from step (3) while it is still hot and quickly add it dropwise to the mixed solution from step (2) while it is being stirred. After about 15 seconds, gel formation can be observed.

[0079] Example 2

[0080] (1) Weigh 30mg of glycyrrhizic acid, add it to a glycerol aqueous solution, heat at 50℃ and stir for 12 minutes to mix thoroughly, then remove and let it cool at room temperature to obtain glycyrrhizic acid hydrogel.

[0081] (2) Place 60 mg of polyvinyl alcohol, 30 mg of glycyrrhizic acid and 1 mL of glycerol aqueous solution in a small glass bottle and mix thoroughly. Heat and stir at 75°C for 12 minutes to obtain a mixed solution.

[0082] (3) Dissolve 140 mg of borax in 1 mL of glycerol aqueous solution, heat at 50 °C and stir until completely dissolved to obtain a borax solution.

[0083] (4) Take the borax solution from step (3) while it is still hot and quickly add it dropwise to the mixed solution from step (2) while it is being stirred. After about 15 seconds, gel formation can be observed.

[0084] Example 3

[0085] (1) Weigh 30mg of glycyrrhizic acid, add it to a glycerol aqueous solution, heat at 70℃ and stir for 7 minutes to mix thoroughly, then remove it and let it cool at room temperature to obtain glycyrrhizic acid hydrogel;

[0086] (2) Mix 60 mg of polyvinyl alcohol, 30 mg of glycyrrhizic acid and 1 mL of glycerol aqueous solution in a small glass bottle, heat and stir at 85 °C for 8 minutes to obtain a mixed solution;

[0087] (3) Dissolve 140 mg of borax in 1 mL of glycerol aqueous solution, heat at 70 °C and stir until completely dissolved to obtain a borax solution.

[0088] (4) Take the borax solution from step (3) while it is still hot and quickly add it dropwise to the mixed solution from step (2) while it is being stirred. After about 15 seconds, gel formation can be observed.

[0089] Example 4

[0090] (1) Weigh 25mg of glycyrrhizic acid, add it to a glycerol aqueous solution, heat at 60℃ and stir for 10 minutes to mix thoroughly, then remove it and let it cool at room temperature to obtain glycyrrhizic acid hydrogel.

[0091] (2) Place 40 mg of polyvinyl alcohol, 25 mg of glycyrrhizic acid and 0.9 mL of glycerol aqueous solution in a small glass bottle and mix thoroughly. Heat and stir at 80 °C for 10 minutes to obtain a mixed solution.

[0092] (3) Separately weigh 120 mg of borax and dissolve it in 1 mL of glycerol aqueous solution. Heat the solution at 60 °C and stir until completely dissolved to obtain a borax solution.

[0093] (4) Take the borax solution from step (3) while it is still hot and quickly add it dropwise to the mixed solution from step (2) while it is being stirred. After about 15 seconds, gel formation can be observed.

[0094] Example 5

[0095] (1) Weigh 35mg of glycyrrhizic acid, add it to a glycerol aqueous solution, heat at 60℃ and stir for 10 minutes to mix thoroughly, then remove it and let it cool at room temperature to obtain glycyrrhizic acid hydrogel.

[0096] (2) Place 80 mg of polyvinyl alcohol, 35 mg of glycyrrhizic acid and 1.5 mL of glycerol aqueous solution in a small glass bottle and mix thoroughly. Heat and stir at 80 °C for 10 minutes to obtain a mixed solution.

[0097] (3) Separately weigh 160 mg of borax and dissolve it in 1.5 mL of glycerol aqueous solution. Heat the solution at 60 °C and stir until completely dissolved to obtain a borax solution.

[0098] (4) Take the borax solution from step (3) while it is still hot and quickly add it dropwise to the mixed solution from step (2) while it is being stirred. After about 15 seconds, gel formation can be observed.

[0099] Example 6

[0100] (1) Weigh 30mg of glycyrrhizic acid, add it to a glycerol aqueous solution, heat at 65℃ and stir for 10 minutes to mix thoroughly, then remove it and let it cool at room temperature to obtain glycyrrhizic acid hydrogel.

[0101] (2) Mix 60 mg of polyvinyl alcohol, 30 mg of glycyrrhizic acid and 1 mL of glycerol aqueous solution in a small glass bottle, heat and stir at 75 °C for 9 minutes to obtain a mixed solution;

[0102] (3) Separately weigh 130 mg of borax and dissolve it in 1.5 mL of glycerol aqueous solution. Heat the solution at 60 °C and stir until completely dissolved to obtain a borax solution.

[0103] (4) Take the borax solution from step (3) while it is still hot and quickly add it dropwise to the mixed solution from step (2) while it is being stirred. After about 15 seconds, gel formation can be observed.

[0104] 2. Animal experiments on the pharmacodynamics of the herbal hydrogel of this invention.

[0105] To verify the efficacy of the herbal hydrogel formulation of this invention, we conducted relevant animal experiments, the contents of which are as follows:

[0106] 2.1 Animal Experiment Section:

[0107] In inducing a mouse psoriasis model using IMQ (imiquimod cream), we systematically recorded changes in erythema, scaling, and epidermal thickening in the modeling area and evaluated them using the PASI score. Results are shown in the attached instructions. Figure 13 As shown, compared with the normal control group, the PASI score of mice in the IMQ model group increased sharply in a time-dependent manner, indicating that the mouse psoriasis model was successfully established. In contrast, all gel treatment groups and the positive drug group showed inhibition of skin lesion progression, with the PF10@PBG group showing the most significant improvement. The other groups also showed varying degrees of remission, as evidenced by a slower increase in PASI score. At the end of treatment, the average PASI score of the PF10@PBG group was significantly lower than that of the model group; the scores of the other treatment groups were also lower than those of the model group. These results fully demonstrate that topical application of PF10@PBG gel can effectively reduce the severity of IMQ-induced psoriasis in mice.

[0108] In addition, we monitored the changes in body weight of mice in each group during model establishment and drug administration. (See attached instructions.) Figure 14 As shown, compared with the blank control group (who showed a slight increase in weight without significant fluctuation) that did not receive IMQ treatment, the IMQ model group mice showed a significant decrease in weight after continuous application, especially in the early stage of modeling, indicating a strong systemic inflammatory and stress response. The positive control group (dexamethasone treatment) mice also showed a significant decrease in weight, which is speculated to be related to the synergistic effect of dexamethasone-induced enhanced catabolic metabolism (promoting muscle and fat degradation) and hypothalamic-pituitary-adrenal axis suppression (HPA axis suppression). In the gel treatment groups, there was a trend of initial decrease followed by increase, but the PF10@PBG group showed an increase on the third day. The weight gain time was delayed in the other groups, suggesting that this gel preparation may have a positive regulatory effect on metabolic status while alleviating systemic inflammation.

[0109] To evaluate the treatment efficacy from a histopathological perspective, we collected skin samples from the backs of mice in each group for H&E staining analysis. (See attached instructions.) Figure 15 As shown, the blank control group had intact skin structure, clear epidermal layers, a thin and dense normal keratinized layer, a continuously visible granular layer, neatly arranged collagen in the dermis, scattered skin appendages, minimal inflammatory cell infiltration, and no obvious pathological changes. The IMQ model group, however, exhibited typical psoriasis-like histological features, including significant acanthosis, hyperkeratosis with parakeratosis, and abundant inflammatory cell infiltration and tortuous capillary dilation in the dermis, indicating a successful establishment of the psoriasis-like dermatitis model. In contrast, both the positive control group and the PF10@PBG gel treatment group showed significant pathological improvement, including reduced epidermal thickness, alleviated keratinization abnormalities, and reduced inflammatory cell infiltration. Among all treatment groups, the PF10@PBG group showed the most significant improvement, with the best restoration of epidermal structure and granular layer continuity, and its tissue morphology most closely resembling normal skin.

[0110] In an IMQ-induced mouse psoriasis model, we analyzed T cell subsets in mouse spleen tissue using flow cytometry. Flow cytometry data showed a significantly increased frequency of Th17 cells in the model group compared to the control group, suggesting that Th17 cells may play a key role in the immunopathology of psoriasis. In the positive control group and all drug-treated groups, the proportion of Th17 cells was downregulated to varying degrees, with the most significant decreases observed in the positive control group and the PF10@PBG group. The experimental results can be found in the appendix to the product manual. Figure 16 The results suggest that this treatment may effectively inhibit Th17 cell activation, thereby alleviating psoriasis-like inflammation. This study reveals the dynamic changes in T cell subsets in spleen tissue under the IMQ model and provides experimental evidence for the immunomodulatory effects of gel drug delivery strategies.

Claims

1. A traditional Chinese medicine hydrogel for treating psoriasis, characterized in that, The hydrogel formulation is made from the following raw materials in the indicated weight ratios: 20-40 parts PVA, 60-80 parts borax, 20-40 parts glycyrrhizic acid, 8-12 parts paeoniflorin, and 2-3 parts glycerin.

2. The traditional Chinese medicine hydrogel preparation as described in claim 1, characterized in that, The hydrogel formulation is made from the following raw materials in the indicated weight ratios: 30 parts PVA, 70 parts borax, 30 parts glycyrrhizic acid, 10 parts paeoniflorin, and 2.5 parts glycerin.

3. The method for preparing the traditional Chinese medicine hydrogel formulation as described in claim 1 or 2, characterized in that, The preparation method includes the following steps: (1) Weigh glycyrrhizic acid, add glycerol aqueous solution, heat at 50~70℃, stir for 7~12 minutes to mix thoroughly, then remove and let stand at room temperature to cool, to obtain glycyrrhizic acid hydrogel; (2) Mix polyvinyl alcohol, glycyrrhizic acid, paeoniflorin and glycerol aqueous solution thoroughly, and heat and stir at 75~85℃ for 8~12 minutes to obtain a mixed solution; (3) Alternatively, borax is dissolved in an aqueous glycerol solution, heated at 50-70°C and stirred until completely dissolved to obtain a borax solution; (4) Take the borax solution from step (3) while it is still hot and quickly add it dropwise to the mixed solution from step (2) while it is being stirred. After about 15 seconds, gel formation can be observed.

4. The method for preparing the traditional Chinese medicine hydrogel formulation as described in claim 3, characterized in that, The preparation method includes step (1) heating at 60°C and stirring for 10 minutes.

5. The method for preparing the traditional Chinese medicine hydrogel formulation as described in claim 3, characterized in that, In step (2) of the preparation method, the heating temperature is 80℃ and the stirring time is 10 minutes.

6. The method for preparing the traditional Chinese medicine hydrogel formulation as described in claim 3, characterized in that, The preparation method step (3) involves heating at 60°C.

7. The use of the traditional Chinese medicine hydrogel preparation as described in any one of claims 1 to 6 in the preparation of a drug for treating psoriasis.

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