PVA-ligusticum wallichii polysaccharide hydrogel as well as preparation method and application thereof

Abstract

The invention relates to the technical field of gels, in particular to PVA-ligusticum wallichii polysaccharide hydrogel and a preparation method and application thereof.The hydrogel comprises PVA, ligusticum wallichii polysaccharide and citric acid, the content of the PVA is 4 wt%-10 wt%, the content of the ligusticum wallichii polysaccharide is 7 wt%-20 wt%, the content of the citric acid is 0.5 wt%-3 wt%, the PVA-ligusticum wallichii polysaccharide hydrogel is of a porous structure, the hydrogel is prepared through a freeze-thaw method, and the hydrogel is prepared through a freeze-thaw method. The gel fraction of the hydrogel is greater than or equal to 60%, and the water absorption expansion rate of the hydrogel is 100-500%; the PVA-ligusticum wallichii polysaccharide hydrogel can release the ligusticum wallichii polysaccharide within 2-10 hours. The PVA-ligusticum wallichii polysaccharide hydrogel provided by the invention has excellent film-forming property, adhesiveness, air permeability and biocompatibility, and provides an ideal carrier for loading and transferring of herbal extracts. By optimizing a gel formula and a preparation process, a gel preparation with stable performance and excellent texture is obtained.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of gels, in particular to a PVA-chuanxiong polysaccharide hydrogel, a preparation method and application thereof. BACKGROUND

[0002] Hydrogels can be used in the biomedical industry for controlled drug delivery systems, wound treatment, dental care, and burn care. Hydrogels also have applications in the field of ophthalmology, particularly in contact lenses. Due to their biocompatibility, providing a sterile wet covering, relatively high water content, and being very similar to real tissue, hydrogels made from hydrophilic polymers can be used for wound treatment. (See DOI: 10.1002 / jbm.a.30308). In addition, soft hydrogels are perfect, structurally strong, but flexible enough to conform to body curves. Due to these same properties, hydrogels can also be used as structuring agents, moisturizers, and / or anti-scarring agents in cosmetic applications. While sterility is not a requirement for hydrogels in cosmetic applications, the absence of polymeric byproducts would be a significant benefit. Hydrogels have the ability to regulate moisture and prevent scarring, among other properties. Due to these properties, hydrogels are the preferred choice for restoring skin vitality, especially facial skin.

[0003] Typically, hydrophilic polymers are crosslinked to form hydrogels. In most cases, hydroxyl radicals generated by ionizing radiation, chemical crosslinking agents, and initiators, or both, cause the polymer chains to crosslink. Chemical crosslinking agents and initiators are added to the polymer solution to generate hydroxyl radicals during the chemical crosslinking process. To be effective for most applications, hydrogels made by chemical crosslinking typically have very low mechanical strength. In addition, chemical crosslinking leaves behind contaminants such as unreacted initiators, crosslinking agents, and chemical reaction byproducts, and the contaminants can be harmful, undesirable, or both. These contaminants require further, expensive, and time-consuming purification procedures. In addition, these hydrogels are often difficult to sterilize. Radiation crosslinking also affects drugs or biologically active compounds present in wound dressings. Citric acid is a chemical crosslinking agent for producing PVA hydrogels. Since citric acid reacts with the hydroxyl groups of PVA mainly through ionic crosslinking, it is considered a biocompatible and safe crosslinking agent.

[0004] Freeze-thaw method is a method that can be used for crosslinking PVA hydrogel. This method does not use any chemical reagents or radiation. It only uses temperature cycling from zero below to room temperature above to induce crosslinking. Therefore, freeze-thaw method is the first choice because it has the least damage to the matrix structure and the drug or therapeutic compound present in the wound dressing. Studies have shown that the freeze-thaw gelation process forms crystalline regions in the PVA microstructure, which act as network junctions. With the increase of freeze-thaw cycle number and temperature domain of freeze-thaw process, the crystallinity and crystal size increase (Macromolecules 2004, 37, 1921-1927, Biomed. Mater. 2012, 7, 015006).

[0005] Natural herbal extracts have the effects of anti-aging and repairing damaged skin. For example, Chuanxiong polysaccharide has the effects of anti-inflammatory, antioxidant, anti-aging, and promoting wound healing, and has a broad application prospect in the skin care field. However, after Chuanxiong polysaccharide is directly added to the emulsion or gel matrix, and stored for a certain period of time, crystallization, precipitation, and delamination may occur, which seriously affects the quality and use experience. At the same time, in vitro skin penetration test shows that free Chuanxiong polysaccharide is easily blocked by the skin barrier and has a low penetration rate, which is not conducive to the exertion of its efficacy. Therefore, developing a new drug delivery system to improve the stability and bioavailability of Chuanxiong polysaccharide in skin care products is one of the main contents of current research. SUMMARY

[0006] The purpose of the present application is to overcome the shortcomings of the prior art, provide a PVA-Chuanxiong polysaccharide hydrogel, a preparation method and application thereof, and creatively combine Chuanxiong polysaccharide with PVA to prepare a hydrogel, and combine the freeze-thaw preparation method, so that the Chuanxiong polysaccharide in the prepared hydrogel has good stability and release performance, and the hydrogel has good film-forming property, adhesion, air permeability and mechanical strength.

[0007] To achieve the above technical effects, the present application adopts the following technical solutions: A PVA-Chuanxiong polysaccharide hydrogel, comprising PVA, Chuanxiong polysaccharide and citric acid, wherein the content of PVA is 4wt%-10wt%, the content of Chuanxiong polysaccharide is 7wt%-20wt%, and the content of citric acid is 0.5wt%-3wt%, preferably, the molecular weight of PVA is 89-98 kDa, and the degree of hydrolysis is >90%; The PVA-Chuanxiong polysaccharide hydrogel has a porous structure, the hydrogel is prepared by freeze-thaw method, the gel fraction of the hydrogel is ≥60%, and the water absorption expansion rate of the hydrogel is 100%-500%; The PVA-Chuanxiong polysaccharide hydrogel can release Chuanxiong polysaccharide within 2h-10h.

[0008] Preferably, the compression strength of the PVA-chuanxiong polysaccharide hydrogel is 0.005-0.050 MPa, and more preferably, the compression strength is 0.010-0.050 MPa.

[0009] Preferably, the compression strain range of the PVA-chuanxiong polysaccharide hydrogel is 260%-620%.

[0010] The application also provides a preparation method of the PVA-chuanxiong polysaccharide hydrogel. S1. Prepare a PVA solution and a citric acid solution respectively, and mix the PVA solution and the citric acid solution to obtain a mixed solution; S2. Disperse chuanxiong polysaccharide in the mixed solution prepared in step S1 to obtain an intermediate solution; S3. Freeze-thaw cycle the intermediate solution to obtain the PVA-chuanxiong polysaccharide hydrogel; In step S3, the freezing temperature of the freeze-thaw cycle is -80℃-10℃, and the thawing temperature is 10℃-35℃.

[0011] Preferably, in step S1, the concentration of PVA in the PVA solution is 5wt%-10wt%, the concentration of citric acid in the citric acid solution is 8wt%-12wt%, and the volume ratio of the PVA solution to the citric acid solution in the mixed solution is (2-11):1, preferably 9:4, 9:3, 9:2, 9:1, 7:1, 11:1, and more preferably 9:1, 7:1.

[0012] Preferably, in step S2, the preparation method of chuanxiong polysaccharide is as follows: 1) Grind dried chuanxiong into powder; 2) Soak 80-120 g of the powder prepared in step 1) in 800-1300 mL of 75% ethanol for 12-36 h, and then perform 2-4 times of reflux extraction, each time for 1-2 h, to obtain a mixture; 3) Filter the mixture prepared in step 2) to remove impurities, and then perform vacuum distillation until the total volume of the mixture is 80-150 mL, to obtain chuanxiong polysaccharide.

[0013] Preferably, in step S2, the volume ratio of chuanxiong polysaccharide to the mixed solution is (2-20):100.

[0014] Preferably, in step S3, in the freeze-thaw cycle, the single freezing time is 6-24 h, and the single thawing time is 6-24 h; and the freeze-thaw cycle is performed for 1-10 cycles in total.

[0015] The application also provides the use of the PVA-chuanxiong polysaccharide hydrogel or the PVA-chuanxiong polysaccharide hydrogel prepared by the above preparation method.

[0016] Preferably, the application is used in the field of oral administration, transdermal administration, drug controlled release, improving cell proliferation activity, promoting cell adhesion and proliferation.

[0017] Preferably, in the above application, the PVA-chuanxiong polysaccharide hydrogel further comprises an additive of a preservative, a drug and an active agent, an antibiotic, an analgesic, an antifungal agent, a humectant, a gelling agent, an antioxidant, a water absorption enhancer and a mixture thereof; The preservative is selected from at least one of sorbate, p-hydroxybenzoate and benzoate; The humectant is selected from at least one of ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, glycerol and hexylene glycol.

[0018] The application also provides a hydrogel product comprising a backing material and a PVA-chuanxiong polysaccharide hydrogel adhered to the backing material, and the backing material is selected from at least one of cloth, fabric, adhesive tape, foam, plastic or paper.

[0019] Compared with the prior art, the application has the following beneficial effects: The application provides a PVA-chuanxiong polysaccharide hydrogel, which has excellent film-forming property, adhesion and air permeability and biocompatibility, and provides an ideal carrier for the loading and delivery of herbal extracts. By optimizing the gel formula and preparation process, a gel preparation with stable performance and excellent texture is obtained.

[0020] A variety of skin care active ingredients, such as flavonoids, polyphenols and saponins, are extracted from natural herbs, and are loaded into the gel matrix through a reasonable process, so that the gel product has good skin care functions such as moisturizing and antioxidant.

[0021] The prepared gel product is subjected to systematic and comprehensive physicochemical property characterization and biological activity evaluation. Scanning electron microscopy reveals the porous three-dimensional network structure of the gel, which is beneficial to the slow release and absorption of active ingredients; rheological test confirms the excellent flowability and thixotropy of the gel, which is convenient for use; according to the comprehensive physicochemical property and biological activity evaluation results, the gel product has a broad application prospect. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 is the SEM image of the PVA-chuanxiong polysaccharide hydrogel provided in Example 2; Figure 2 is the cytotoxicity result provided in Experimental Example 3; Figure 3 is the hydrogel swelling curve provided in Experimental Example 1; Figure 4 is the hydrogel curve of different PVA proportions provided in Experimental Example 1; Figure 5 is the hydrogel curve of different citric acid ratios provided by experimental example 1; Figure 6 is the release curve of polysaccharide of Chuanxiong Rhizoma of the hydrogel provided by experimental example 3; Figure 7 is the UV absorption fitting curve of the polysaccharide of Chuanxiong Rhizoma released by the hydrogel provided by experimental example 3; Figure 8 is the compression mechanical strength curve of the hydrogel provided by experimental example 1. DETAILED DESCRIPTION

[0023] The application will be further described below in conjunction with the drawings and examples.

[0024] The raw materials and experimental equipment used in the examples, comparative examples and experimental examples are all commonly used commercially available raw materials and equipment in the art, and the specific sources are not described here. Among them, the molecular weight of PVA is 89-98 kDa, and the degree of hydrolysis is >90%.

[0025] Example 1 8 grams of polyvinyl alcohol (PVA) was mixed with 92 milliliters of pure water, heated to 95°C, and stirred for 4 hours to obtain solution 1; 10 grams of citric acid (CA) was mixed with 90 milliliters of water, and stirred until completely dissolved to obtain solution 2: First group (P9C4): solution 1 and solution 2 were mixed in a ratio of 9:4 to obtain solution 3, and the volume of solution 3 was 13 mL; Second group (P9C3): solution 1 and solution 2 were mixed in a ratio of 9:3 to obtain solution 3, and the volume of solution 3 was 12 mL; Third group (P9C2): solution 1 and solution 2 were mixed in a ratio of 9:2 to obtain solution 3, and the volume of solution 3 was 11 mL; Fourth group (P9C1): solution 1 and solution 2 were mixed in a ratio of 9:1 to obtain solution 3, and the volume of solution 3 was 10 mL; Fifth group (P7C1): solution 1 and solution 2 were mixed in a ratio of 7:1 to obtain solution 3, and the volume of solution 3 was 8 mL; Sixth group (P11C1): solution 1 and solution 2 were mixed in a ratio of 11:1 to obtain solution 3, and the volume of solution 3 was 12 mL.

[0026] The above 6 groups of solution 3 were subjected to freeze-thaw cycles, and each cycle was under the condition of freezing at -18°C for 12h and thawing at 20°C for 12h, and the freeze-thaw cycles were performed for a total of 2 cycles to form stable hydrogels with good mechanical strength.

[0027] Example 2 This embodiment discloses a PVA-Ligusticum chuanxiong polysaccharide hydrogel, wherein the PVA content is 6 wt%, the Ligusticum chuanxiong polysaccharide content is 5.5 wt%, the citric acid content is 0.83 wt%, and the gel fraction is 61%. Its preparation method includes the following steps: S1. Prepare PVA solution and citric acid solution separately, and mix them well to obtain a mixed solution. Mix 8 g of PVA with 92 mL of pure water, heat to 95 °C, and stir for 4 hours (solution 1); mix 10 g of citric acid with 90 mL of water and stir until completely dissolved (solution 2); mix solution 1 and solution 2 at a volume ratio of 9 mL: 1 mL to obtain solution 3, with a volume of 10 mL. S2. Take 1 mL of Ligusticum chuanxiong polysaccharide and disperse it in the mixed solution (solution 3) prepared in step S1 to obtain an intermediate solution (solution 4). The total volume of the intermediate solution is 11 mL. The preparation method of Ligusticum chuanxiong polysaccharide is as follows: 1) Grind dried Sichuan lovage root into powder; 2) Take 80g of the powder obtained in step 1) and soak it in 900mL of 75% ethanol for 24h. Then, perform reflux extraction 3 times, 2h each time, to obtain a mixture. 3) After filtering the mixture obtained in step 2) to remove impurities, distill under reduced pressure until the total volume of the mixture is 120 mL, thus obtaining Ligusticum chuanxiong polysaccharide. S3. The intermediate solution (solution 4) is subjected to freeze-thaw cycles. The conditions for each cycle are freezing at -20℃ for 18 hours and thawing at 25℃ for 6 hours. The freeze-thaw cycles are performed twice in total to obtain PVA-Ligusticum chuanxiong polysaccharide hydrogel.

[0028] like Figure 1 As shown, the PVA-Ligusticum chuanxiong polysaccharide hydrogel prepared in this embodiment exhibits a clearly visible porous structure. The pores are relatively uniformly distributed, displaying a typical interconnected network. A pore size distribution curve can be obtained by measuring the diameter of multiple pores. The pore size is mainly concentrated between 50-200 nm and has a narrow distribution, indicating that the gel has good pore size consistency. A suitable pore size is beneficial for drug molecule loading and sustained release. Figure 1 The microstructure of the gel surface is shown, with some wrinkles and undulations, exhibiting a moderate roughness.

[0029] Example 3 This embodiment discloses a method for preparing PVA-Ligusticum chuanxiong polysaccharide hydrogel: S1. Prepare PVA solution and citric acid solution separately, and mix them well to obtain a mixed solution. 8 g PVA was mixed with 92 mL pure water, heated to 95 °C, and stirred for 4 hours (solution 1); 10 g citric acid was mixed with 90 mL water and stirred until completely dissolved (solution 2), solution 1 and solution 2 were mixed in a volume ratio of 9 mL: 1 mL to obtain solution 3, the volume of solution 3 was 10 mL; S2. 1 mL of Chuanxiong polysaccharide was dispersed in the mixed solution (solution 3) prepared in step S1 to obtain an intermediate solution (solution 4), the total volume of the intermediate solution was 11 mL, The preparation method of Chuanxiong polysaccharide is as follows: 1) The dried Chuanxiong was ground into powder; 2) 80 g of the powder prepared in step 1) was soaked in 900 mL of 75% ethanol for 24 h, then extracted by reflux for 3 times, each time for 2 h, to obtain a mixture; 3) The mixture prepared in step 2) was filtered to remove impurities, then distilled under reduced pressure until the total volume of the mixture was 120 mL, thereby obtaining Chuanxiong polysaccharide, S3. The intermediate solution (solution 4) was subjected to freeze-thaw cycles, each cycle being frozen at -20 °C for 18 h and thawed at 25 °C for 6 h, and the freeze-thaw cycles were performed for a total of 2 cycles, thereby obtaining a PVA-Chuanxiong polysaccharide hydrogel.

[0030] Experimental Example 1 Cytotoxicity test The experimental protocol for the cytotoxicity test was the MTT test. The test included the following experimental groups: PVA (not crosslinked), PVA / Chuanxiong (not crosslinked), PVA / Chuanxiong / FT (crosslinked only by freeze-thawing), PVA / Chuanxiong / FT / citric acid (PVA-Chuanxiong polysaccharide hydrogel prepared according to the method of Example 3), and PVA / GA crosslinked by glutaraldehyde. Human dermal fibroblasts (HDF) were prepared and cultured in 96-well plates. 0.1 g of HDF was soaked in culture medium for each experimental group, and after 24 hours, the culture medium in the plate was replaced with the culture medium in contact with the experimental group. The control wells used fresh culture medium. After 24 hours of plate culture, the culture medium was replaced with MTT solution and incubated for 4 hours, then the MTT solution was replaced with dimethyl sulfoxide and incubated for 15 minutes, and finally the absorbance of the wells was read by Elisa Reader. The absorbance of the control wells was considered to be 100% cell survival rate, and the absorbance of the other experimental groups was divided by the absorbance of the control wells to be considered the cell survival rate of the experimental group.

[0031] The cytotoxicity results are as follows: Figure 2As shown, pure PVA exhibits no cytotoxicity towards human fibroblasts. The addition of Ligusticum chuanxiong did not significantly alter the cytotoxicity. The PVA-Ligusticum chuanxiong / FT sample, cross-linked using a freeze-thaw method, demonstrates that freeze-thaw cross-linking has no cytotoxicity towards fibroblasts. The addition of citric acid also did not produce any cytotoxicity. The PVA / GA sample shows cytotoxicity data for PVA hydrogels cross-linked with the chemical cross-linking agent glutaraldehyde. It can be seen that the cell viability of the PVA / GA sample is below 60%, which is unacceptable for skincare products or other biomedical applications. All other samples showed cell viability above 90%, comparable to the control group, indicating their safety for use in skincare products.

[0032] Experiment Example 2 The release experiment of Ligusticum chuanxiong polysaccharide was conducted using the PVA-Ligusticum chuanxiong polysaccharide hydrogel prepared in Example 3: First, prepare a solution of chuanxiong (Ligusticum striatum) at a known concentration in water, measure the absorbance, and then... Figure 7 Then, the PVA / CA / Ligusticum striatum hydrogel was placed in water, and small amounts of water were collected at different time points to determine the concentration of released Ligusticum striatum. The absorbance was measured, and the results were analyzed according to... Figure 7 The concentration was determined using a linear regression formula. Concentrations measured at different time points were plotted. Figure 6 , Figure 6 It shows the release status at different points in time.

[0033] like Figure 6 and Figure 7 As shown, the dissolution test confirms that it can be continuously released, with a cumulative penetration of 20.76% after 9 hours. PVA is a natural polymer material with excellent moisturizing properties. The PVA-Ligusticum chuanxiong gum hydrogel prepared in this invention can fully utilize the moisturizing effect of PVA and effectively improve the skin's moisture status.

[0034] Experimental Example 3 The swelling rate was tested using six groups of hydrogels prepared in Example 1: In the expansion test, the weight of the dried sample (W0) was first measured, and then it was immersed in water. The weight of the expanded sample (W1) was measured at different time points. The expansion rate at each time point was calculated according to the following formula: Expansion rate = (W1 - W0) / W0 × 100%, and the results are as follows. Figures 3-5 As shown.

[0035] like Figure 3 As shown, the swelling ratio of the composite hydrogel increases with increasing citric acid content. Sample P9C4 exhibits the highest swelling ratio, reaching 500%. Reducing the proportion of citric acid decreases the swelling ratio. The results indicate that the lower the degree of cross-linking of the cross-linked polymer, the higher the swelling degree. With increasing solution volume, the polymer chains have more space to move during water absorption, leading to a greater degree of expansion.

[0036] Experiment Example 4 The mechanical strength of the hydrogels was tested using the six groups of hydrogels prepared in Example 1. In compression mode, the hydrogel is placed in a universal testing machine. A force is then applied at a constant strain rate. Stress-strain curves are derived using force-displacement data. The maximum stress in the graph is considered the compressive strength of the hydrogel.

[0037] like Figure 8 As shown, the material exhibits a nonlinear stress-strain relationship, indicating that the gel is a nonlinear elastic material. The stress increases with increasing strain, indicating that the material possesses certain strength and stiffness. The strain reaches its maximum value of 620% when the stress reaches 0.022 MPa. The data points are not arranged exactly in the order of increasing strain, which may be due to experimental errors during the testing process or the non-homogeneity of the material.

Claims

1. A PVA-Chuanxiong polysaccharide hydrogel, characterized in that, The PVA-chuanxiong polysaccharide hydrogel comprises PVA, chuanxiong polysaccharide and citric acid, wherein the content of PVA is 4wt%-10wt%, the content of chuanxiong polysaccharide is 7wt%-20wt%, and the content of citric acid is 0.5wt%-3wt%. The PVA-chuanxiong polysaccharide hydrogel has a porous structure, is prepared by a freeze-thaw method, has a gel fraction of ≥60%, and has a water absorption expansion rate of 100%-500%. The PVA-chuanxiong polysaccharide hydrogel can release chuanxiong polysaccharide within 2h-10h.

2. The PVA- chuanxiong polysaccharide hydrogel of claim 1, wherein, The compression strength of the PVA-chuanxiong polysaccharide hydrogel is 0.005MPa-0.050MPa, and the compression strain range of the PVA-chuanxiong polysaccharide hydrogel is 260%-620%.

3. The PVA- chuanxiong polysaccharide hydrogel of claim 1, wherein, The compression strength is 0.010MPa-0.050MPa.

4. The preparation method of the PVA-chuanxiong polysaccharide hydrogel according to any one of claims 1-3, comprising the following steps: S1. Prepare PVA solution and citric acid solution respectively, and mix the PVA solution and the citric acid solution to obtain a mixed solution; S2. Disperse chuanxiong polysaccharide in the mixed solution prepared in step S1 to obtain an intermediate solution; S3. Freeze-thaw cycle the intermediate solution to obtain the PVA-chuanxiong polysaccharide hydrogel; In step S3, the freezing temperature of the freeze-thaw cycle is -80℃~-10℃, and the thawing temperature is 10℃~35℃.

5. The production method according to claim 4, wherein In step S1, the concentration of PVA in the PVA solution is 5wt%-10wt%, the concentration of citric acid in the citric acid solution is 8wt%-12wt%, and the volume ratio of the PVA solution to the citric acid solution in the mixed solution is (2-11):

1.

6. The production method according to claim 4, wherein In step S2, the preparation method of chuanxiong polysaccharide is as follows: 1) Grind dried chuanxiong into powder; 2) Soak 80g-120g of the powder prepared in step 1) in 800mL-1300mL of 75% ethanol for 12-36h, then perform 2-4 times of reflux extraction, each time for 1h-2h, to obtain a mixture; 3) Filter the mixture prepared in step 2) to remove impurities, and distill under reduced pressure until the total volume of the mixture is 80mL-150mL, to obtain chuanxiong polysaccharide.

7. The production method according to claim 4, wherein In step S2, the volume ratio of chuanxiong polysaccharide to the mixed solution is (2-20):100; In step S3, in the freeze-thaw cycle, the single freezing time is 6h-24h, and the single thawing time is 6h-24h; the freeze-thaw cycle is performed for 1-10 cycles in total.

8. The production method according to claim 4, wherein The volume ratio of the PVA solution to the citric acid solution is 9:

1.

9. The PVA-chuanxiong polysaccharide hydrogel according to any one of claims 1-3 or the PVA-chuanxiong polysaccharide hydrogel prepared by the preparation method according to any one of claims 4-8.

10. The use according to claim 9, wherein the compound is ###0002### It is used in the fields of oral administration, transdermal administration, drug controlled release, improvement of cell proliferation activity, and promotion of cell adhesion and proliferation.

Images