Preparation method and application of drug label based on structural color hydrogel

Abstract

The present invention provides a preparation method and application of a drug label based on structural color hydrogel, which relates to the field of biomedical technology. The drug label based on structural color hydrogel is prepared by the following formula: HPC, 5% gelatin solution, HMPP, liquid paraffin and Span 80 with a mass ratio of 55-63:27-45:1:100:2, and the drug label of the structural color hydrogel also includes 0.01 parts of CeO2 or 10 parts of chitosan solution by mass ratio, and the chitosan solution is a chitosan solution with a concentration of 0.5%. In this application, 6W female BALB / c mice were selected and divided into a healthy control group, an IMQ administration group, an IMQ+CeO2 administration group, an IMQ+CS administration group, and an IMQ+CeO2+CS administration group. The disease degree of psoriasis mice was observed after 6 days of treatment. In the present invention, it is proved through specific verification experiments that the hydrogel based on structural color prepared in the present application can effectively improve the condition of psoriasis mice.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to a preparation method of a drug label based on structural color hydrogel and application thereof. Background Art

[0002] Psoriasis, commonly known as "psoriasis", is a skin disease stimulated by environmental factors, controlled by polygenic inheritance, and mediated by immunity. It is typically manifested as scaly erythema or plaques, which are confined to one place or widely distributed throughout the body. Most patients experience aggravation or relapse in winter and relief in summer.

[0003] Although the incidence of psoriasis in the Chinese population is lower than that in Europe and the United States, psoriasis still plagues millions of people due to the large population base in my country. Many factors are believed to be related to the occurrence of psoriasis, including environment, genetics, and immune system disorders. But so far, there is no cure for psoriasis. The treatment goals of psoriasis include controlling the disease, slowing the progression of development, reducing skin damage, and avoiding recurrence as much as possible. Current clinical treatments aim to use biological agents (such as monoclonal antibodies against interleukin-17 (IL-17)) or topical corticosteroids, which are effective ways to treat psoriasis by reducing psoriasis cytokines or direct immunosuppression. However, long-term immunosuppression increases the risk of infection and even the occurrence of tumors. Therefore, we urgently need to explore more treatment options. Summary of the invention

[0004] The purpose of the present invention is to solve the lack of solutions for the treatment of psoriasis in the prior art, and to provide a method for preparing a drug label based on structural color hydrogel. The hydrogel mentioned in this application has good adhesion and skin retention, and can have adjustable functions by incorporating various nanoparticles, so it has broad application prospects in the treatment of skin diseases.

[0005] And because of its natural structural color, HPC hydrogel can be used as a drug label to achieve clearer drug delivery. Cerium dioxide nanozymes have multiple enzyme activities such as SOD-like enzyme activity, ·OH scavenging ability, and CAT-like enzyme activity, so they can remove excess ROS and reduce inflammatory responses. Therefore, they have broad application scenarios in various inflammatory diseases. Chitosan is a naturally positively charged substance that can remove free DNA and combine with bacterial cell membranes to achieve a bactericidal effect. Due to its natural low toxicity, it is widely used as a drug delivery material in various diseases.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] A method for preparing a drug label based on structural color hydrogel. The drug label based on structural color hydrogel is prepared by the following formula: HPC, 5% gelatin solution, HMPP, liquid paraffin and Span 80 in a mass ratio of 55-63:27-45:1:100:2. The drug label of the structural color hydrogel also includes 0.01 parts of CeO2 or 10 parts of chitosan solution in a mass ratio, and the chitosan solution is a chitosan solution with a concentration of 0.5%.

[0008] Preferably, the method comprises the following steps:

[0009] S1: Material preparation

[0010] Prepare the materials mentioned above;

[0011] S2: Preparation of hydrogel solution

[0012] Weigh HPC, CeO2 / chitosan solution and 5% gelatin solution and mix them evenly to obtain a hydrogel solution;

[0013] S3: Decentralized

[0014] The hydrogel solution obtained in S2 was added to liquid paraffin and Span 80 and dispersed using a disperser;

[0015] S4: Use liquid paraffin to wash away the residual foam in the S3 solution to obtain a drug label based on structural color hydrogel.

[0016] Preferably, in S2, HPC, CeO2 / CS and 5% gelatin solution are mixed, stirred evenly at 50°C, and then centrifuged at 16000 rpm for 60 minutes to obtain a hydrogel solution.

[0017] Preferably, the dispersion condition in S3 is 5000 rpm for two minutes.

[0018] The present application also provides a drug label based on structural color hydrogel, characterized in that it is prepared using the above-mentioned preparation method.

[0019] The present application also provides an application of a drug label based on structural color hydrogel in the preparation of a drug for treating psoriasis. The drug label based on structural color hydrogel is prepared using the preparation method described above.

[0020] In summary, the present application experimentally verified that imiquimod (IMQ)-induced mice are a recognized disease model of psoriasis mice. The hydrogel treatment of the drug-administered group significantly reduced the disease activity of imiquimod (IMQ)-induced psoriasis mice. Skin HE showed that the thickness of the epidermis was significantly reduced, and the spleen index showed that the spleen index of the mice in the treatment group was reduced. Immunohistochemistry showed that the expression of Ki-67 and IL-17A in the treatment group mice was significantly reduced. Plasma ELISA showed that the levels of IL-1β and TGF-β in the treatment group mice decreased. Therefore, the present invention explores the feasibility of using a structural color hydrogel to treat psoriasis by using an imiquimod (IMQ)-induced mouse psoriasis model. Through the experiments in the embodiments of the present invention, it can be concluded that the structural color hydrogel prepared in the present application is a new treatment for psoriasis. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is the structural color HPC hydrogel in the embodiment of the present invention. Figure 1 a. Different concentrations of HPC form different structural colors. Figure 1 b, Spectra of the structural colors of HPC hydrogels with different concentrations. Figure 1 c. Structural color microspheres formed after HPC hydrogels of different concentrations were dispersed in liquid paraffin (scale bar: 500 μm).

[0022] Figure 2 This is a mouse model of psoriasis treated with structural color hydrogel in an embodiment of the present invention. Figure 2 a. Flowchart of drug administration. Figure 2 b, Representative images of the back skin of mice in each group during drug administration. Figure 2 c. Body weight of mice in each group during drug administration. Figure 2 d. Skin activity scores of mice in each group 6 days after administration. Figure 2 e. Representative HE images of the skin of mice in each group (scale bar: 100 μm, scale bar: 200 μm). Figure 2 f. Statistics of epidermal thickness of the skin of mice in each group.

[0023] Figure 3 This is a mouse after administration of the structural color hydrogel in the example of the present invention. Figure 3 a, Representative HE images of spleen of mice in each group (scale bar: 200 μm). Figure 3 b, Representative images of spleens from mice in each group. Figure 3 c. Statistical graph of spleen index of mice in each group. Figure 3 d, Representative immunohistochemical images of Ki-67 and IL-17A in each group of mice (scale bar: 100 μm). Figure 3 e. Statistical graph of Ki-67 immunohistochemistry in mice. Figure 3f. Statistical graph of IL-17A immunohistochemistry in mice. Figure 3 g. Plasma IL-1β levels of mice in each group. Figure 3 h. Plasma TGF-β levels of mice in each group. DETAILED DESCRIPTION

[0024] The present invention is further described in detail below in conjunction with specific embodiments.

[0025] English Explanation of Some of the Articles

[0026] English Interpretation HPC Hydroxypropyl Cellulose <![CDATA[CeO2]]> Cerium Oxide HMPP 2-Hydroxy-2-methyl-1-phenyl-1-propanone CS Chitosan IMQ Imiquimod

[0027] The present application provides a method for preparing a drug label based on structural color hydrogel, comprising the following steps:

[0028] S1: Material preparation

[0029] In one embodiment, the structural color hydrogel-based drug label is prepared by the following formula: HPC, 5% gelatin solution, HMPP, liquid paraffin and Span 80 in a mass ratio of 55-63:27-45:1:100:2, and the structural color hydrogel drug label also includes 0.01 parts of CeO2 or 10 parts of a 0.5% concentration chitosan solution in a mass ratio.

[0030] S2: Mixing to prepare hydrogel solution

[0031] HPC, CeO2 and 5% gelatin solution were weighed and mixed, stirred evenly at 50°C, and centrifuged at 16000 rpm for 60 min to obtain a hydrogel solution.

[0032] S3: Decentralized

[0033] The hydrogel solution obtained in S2 was added to liquid paraffin and Span 80, and dispersed using a disperser at 5000 rpm for two minutes.

[0034] S4: Wash off the foam

[0035] Liquid paraffin was used to wash away the residual foam in the solution in S3 to obtain a drug label based on structural color hydrogel.

[0036] The present application also provides a drug label based on structural color hydrogel, which is prepared using the above preparation method.

[0037] Secondly, the present application also provides the use of the above-mentioned drug label in the preparation of drugs for treating psoriasis.

[0038] The above contents of this application are verified by combining specific verification experiments as follows:

[0039] Example 1: Different concentrations of HPC form different structural color hydrogels

[0040] 1.1 Experimental methods:

[0041] Weigh different masses of HPC, 6.3g, 5.9g, and 5.5g, add 5% gelatin solution to make up to 10g, and add 0.1g HMPP, stir evenly at 50℃, and centrifuge at 16000rpm for 60min. Weigh 1g of the above HPC hydrogels of different concentrations, add 10g liquid paraffin and 0.1g Span 80. Use a disperser to disperse at 5000rpm for two minutes. Wash off the remaining foam with liquid paraffin.

[0042] 1.2 Experimental results:

[0043] HPC hydrogels with different concentrations generate blue, green, and red structural colors, respectively. Figure 1 As shown in a. With the increase of concentration, the reflection peak of the color red-shifts, indicating flexible structural color coding, such as Figure 1 b. In addition, optical microscopy images showed the uniform morphology and size of these colored hydrogel droplets, as shown in Figure 1 As shown in c.

[0044] Example 2: Structural color hydrogel improves disease activity in psoriasis mice

[0045] 2.1 Experimental methods:

[0046] 6-week female BALB / c mice were selected and divided into a healthy control group, an IMQ administration group, an IMQ+CeO2 administration group, an IMQ+CS administration group, and an IMQ+CeO2+CS administration group.

[0047] Weigh 6.3 g of HPC, mix evenly with 1 g of 0.5% chitosan solution, 2.7 g of 5% gelatin solution and 0.1 g of HMPP, and then disperse in liquid paraffin and Span 80 to prepare hydrogel droplets containing CS;

[0048] 5.5 g of HPC and 1 mg of cerium dioxide were weighed, mixed evenly with 4.5 g of 5% gelatin solution and 0.1 g of HMPP, and then dispersed in liquid paraffin and Span 80 to prepare hydrogel droplets containing CeO2 structural color markers.

[0049] The day before administration, the mice were depilated on their backs to form a 2*3.5cm 2 Hairless areas. Figure 2 As shown in a, the treatment group was given hydrogel treatment simultaneously with daily IMQ.

[0050] Specifically, the IMQ+CeO2 administration group was given treatment with CeO2 structural color-labeled hydrogel microdroplets while receiving daily IMQ;

[0051] The IMQ+CS group was given CS-containing hydrogel treatment at the same time as daily IMQ;

[0052] The IMQ+CeO2+CS group was co-treated with CeO2 structural color-labeled hydrogel microdroplets and CS-containing hydrogel while receiving daily IMQ;

[0053] The mice were killed after 6 consecutive days of drug administration. The mice were weighed and photographed daily during the drug administration period. The skin of the drug administration area was collected after the mice were killed, and HE staining was performed to calculate the average epidermal thickness of mice in each group.

[0054] 2.2 Experimental results:

[0055] like Figure 2 As shown in b, the body weight of mice in the IMQ-treated group decreased significantly compared with the mice in the healthy control group;

[0056] like Figure 2 As shown in c, IMQ administration successfully induced skin inflammation, with symptoms of erythema and desquamation, indicating the onset of psoriasis, and the skin inflammation, erythema, and desquamation symptoms of mice in the IMQ+CeO2 administration group, IMQ+CS administration group, and IMQ+CeO2+CS administration group were significantly milder than those in the IMQ administration group;

[0057] like Figure 2 As shown in d, the PASI scores indicated that the disease activity of mice in the IMQ+CeO2 administration group, IMQ+CS administration group, and IMQ+CeO2+CS administration group was lower than that in the IMQ administration group;

[0058] like Figure 2 As shown in e, hematoxylin-eosin (HE) staining showed that the epidermal thickness of mice in the IMQ+CeO2+CS administration group, IMQ+CeO2 administration group, and IMQ+CS administration group was significantly decreased compared with that of mice in the IMQ administration group;

[0059] like Figure 2 As shown in f, the statistics of epidermal thickness showed that the epidermal thickness of mice in the IMQ+CeO2+CS administration group, IMQ+CeO2 administration group and IMQ+CS administration group was significantly decreased compared with that in the IMQ administration group.

[0060] Example 3: Structural color hydrogel droplets significantly inhibited inflammation in psoriasis mice.

[0061] 3.1 Experimental methods:

[0062] The spleen of each group of mice was weighed and photographed, and then embedded in paraffin and sliced ​​for HE staining. Immunohistochemistry was used to observe the expression of factors such as Ki-67 and IL-17A in the mouse skin. Elisa was used to measure the expression of inflammatory factors such as IL-1β and TGF-β in mouse plasma.

[0063] 3.2 Experimental results:

[0064] HE analysis of mouse spleen showed that the spleen cells of mice in the IMQ+CeO2+CS, IMQ+CeO2 and IMQ+CS groups were densely arranged, especially in the IMQ+CeO2+CS group, indicating that no lesions occurred in the spleen after intervention. Figure 3 As shown in a;

[0065] Mice in the IMQ-administered group developed splenomegaly, but the condition was slightly alleviated by the treatment with CeO2+CS administration, as shown in 3b;

[0066] The spleen index showed that the situation of IMQ+CeO2+CS administration group was similar to that of the healthy control group, such as Figure 3 As shown in c;

[0067] Immunohistochemistry showed that the skin lesions of mice in the IMQ administration group expressed Ki-67 and IL-17A more strongly than those in the healthy control group. The expression of Ki-67 and IL-17a in the IMQ+CeO2+CS administration group was significantly decreased. Figure 3 As shown in d;

[0068] The immunohistochemical statistical results showed that the positive rates of Ki-67 and IL-17a in the IMQ+CeO2+CS group were significantly lower than those in the IMQ group. Figure 3 ef shown;

[0069] Elisa results showed that the levels of pro-inflammatory factors such as IL-1β and TGF-β in the plasma of mice in the IMQ+CeO2+CS group were significantly lower than those in the IMQ group. Figure 3 As shown in g and h.

[0070] In summary, the present application experimentally verified that imiquimod (IMQ)-induced mice are a recognized disease model of psoriasis mice. The hydrogel treatment of the drug-administered group significantly reduced the disease activity of imiquimod (IMQ)-induced psoriasis mice. Skin HE showed that the thickness of the epidermis was significantly reduced, and the spleen index showed that the spleen index of the mice in the treatment group was reduced. Immunohistochemistry showed that the expression of Ki-67 and IL-17A in the treatment group mice was significantly reduced. Plasma ELISA showed that the levels of IL-1β and TGF-β in the treatment group mice decreased. Therefore, the present invention explores the feasibility of using a structural color hydrogel to treat psoriasis by using an imiquimod (IMQ)-induced mouse psoriasis model. Through the experiments in the embodiments of the present invention, it can be concluded that the structural color hydrogel prepared in the present application is a new treatment for psoriasis.

Claims

1. A method for preparing a drug label based on structural color hydrogel, characterized in that: The drug label based on the structural color hydrogel is prepared by the following formula: HPC, 5% gelatin solution, HMPP, liquid paraffin and Span 80 in a mass ratio of 55-63:27-45:1:100:2, and the drug label of the structural color hydrogel also includes 0.01 parts of CeO2 or 10 parts of chitosan solution in a mass ratio, and the chitosan solution is a chitosan solution with a concentration of 0.5%; specifically comprising the following steps: S1: Material preparation Prepare the ingredients as described in the recipe; S2: Preparation of hydrogel solution Weigh HPC, CeO2 / chitosan solution, 5% gelatin solution and HMPP and mix them evenly to obtain a hydrogel solution; S3: Decentralized The hydrogel solution obtained in S2 was added to liquid paraffin and Span 80 and dispersed using a disperser; S4: Use liquid paraffin to wash away the residual foam in the S3 solution to obtain a drug label based on structural color hydrogel.

2. The method for preparing a drug label based on structural color hydrogel according to claim 1, characterized in that: In the S2, HPC, CeO2 / chitosan solution and 5% gelatin solution are mixed, stirred evenly at 50°C, and then centrifuged at 16000 rpm for 60 min to obtain a hydrogel solution.

3. The method for preparing a drug label based on structural color hydrogel according to claim 2, characterized in that: The dispersion condition in S3 is 5000 rpm for two minutes.

4. A drug label based on structural color hydrogel, characterized in that: The method is used to prepare the product according to any one of claims 1 to 3.

5. Application of a drug label based on structural color hydrogel in the preparation of a drug for treating psoriasis, characterized in that: The drug label based on structural color hydrogel is prepared using the preparation method described in any one of claims 1 to 3.

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