Application of stable silicic acid aqueous solution in preparation of product for treating psoriasis

Abstract

The invention relates to an application of a stable silicic acid aqueous solution in preparation of a product for treating psoriasis, and the mass concentration of the stable silicic acid aqueous solution is 0.5-2%. The stable silicic acid aqueous solution serves as an active component, and psoriasis can be treated at the mass concentration of 0.5%-2%. Meanwhile, the stable silicic acid aqueous solution is low in raw material cost, environment-friendly and safe, and can be used as a safe alternative medicament for treating psoriasis with a good curative effect.

Description

TECHNICAL FIELD

[0001] The application relates to the field of biological medicine, in particular to application of a stable silicic acid aqueous solution in preparation of a product for treating psoriasis. BACKGROUND

[0002] Psoriasis is a chronic autoimmune skin disease that is difficult to completely cure and recurs, and affects about 2-3% of the population in the world, and is characterized by the appearance of raised, scaly, red or pink patches on the skin, the size and shape of the patches are different, and the patches are covered with white scales and can occur on any part of the body, commonly on the elbows, knees, scalp, lower back and nail parts of patients. The most prominent pathological feature of psoriasis is the abnormal growth and differentiation of keratinocytes. In addition, this abnormal growth and differentiation of keratinocytes is accompanied by skin inflammation, which is characterized by an increase in immune cell infiltration in the skin, including T cells, neutrophils and dendritic cells. These immune cells release cytokines and other inflammatory mediators, further exacerbating skin inflammation, leading to various symptoms of psoriasis. The exact cause of psoriasis is not yet known, and it is currently believed to be caused by a combination of genetic, environmental and immune system factors.

[0003] At present, psoriasis is mainly divided into five types in clinical practice, namely, psoriasis vulgaris, pustular psoriasis, erythrodermic psoriasis, arthropathic psoriasis and psoriasis comorbidity. There is no cure for the disease at present. The treatment mainly focuses on controlling the disease, slowing down the development of the disease and improving the quality of life of patients, while trying to reduce the adverse reactions of patients. Systemic treatment mainly includes acitretin, methotrexate, cyclosporine, apremilast, etc., but these drugs have potential toxicity to the liver, kidney and bone marrow, or have teratogenic effects; external drugs such as corticosteroids, vitamin D analogues, calcineurin inhibitors, etc.; and can also be combined with photochemical therapy such as long-wave ultraviolet light combined with psoralen (PUVA) or UVB irradiation. SUMMARY

[0004] The purpose of the present application is to solve the problem of potential toxicity to the liver, kidney and bone marrow of the drugs used in systemic treatment at present, and to propose an alternative drug, which is a product for treating psoriasis prepared from a stable silicic acid aqueous solution, so as to obtain better efficacy.

[0005] To achieve the above-mentioned purpose, the application provides application of a stable silicic acid aqueous solution in preparation of a product for treating psoriasis, wherein the mass concentration of the stable silicic acid aqueous solution is 0.5%-2%.

[0006] Further, when used externally, the stable silicic acid aqueous solution is dispersed in an ointment base as an active ingredient.

[0007] Further, the application provides a product for treating psoriasis, an active ingredient of the product being a stable silicic acid aqueous solution with a mass concentration of 0.5% to 2%, and the product being a medical device or a drug.

[0008] Based on the above technical solution, the application has the following advantages:

[0009] The stable silicic acid aqueous solution as the active ingredient can treat psoriasis at a mass concentration of 0.5% to 2%. Meanwhile, the stable silicic acid aqueous solution has low raw material cost and is environmentally friendly and safe, and can be used as a safe and effective alternative drug for treating psoriasis. BRIEF DESCRIPTION OF DRAWINGS

[0010] The accompanying drawings, which are included to provide a further understanding of the application and are incorporated in and constitute a part of this application, illustrate embodiments of the application and serve to explain the principles of the application, and do not limit the application. In the drawings:

[0011] Figure 1 Photos of changes in the back skin of a psoriasis mouse model at 0, 3, 5 and 7 days;

[0012] Figure 2 A PASI score result graph of a psoriasis mouse;

[0013] Figure 3 A spleen index graph of a psoriasis mouse;

[0014] Figure 4 A photo of the spleen of a psoriasis mouse model;

[0015] Figure 5 An HE staining pathological graph of the back skin of a psoriasis mouse. DETAILED DESCRIPTION

[0016] The technical solution of the application will be further described below with reference to the accompanying drawings and embodiments.

[0017] The application provides application of a stable silicic acid aqueous solution in preparation of a product for treating psoriasis, wherein the mass concentration of the stable silicic acid aqueous solution is 0.5% to 2%.

[0018] It should be noted that the stable silicic acid aqueous solution in the application is a stable stable silicic acid aqueous solution, wherein the stable silicic acid aqueous solution refers to a stable solution without polymerization, and the main components include monosilicic acid (H4SiO4), metasilicic acid (H2SiO3) and hydrogen silicate (HSiO3 -), the mass concentration in the present application is 0.5% to 2%, which refers to the total concentration of the main components being 0.5% to 2%. In the present application, in order to concisely represent the stable silicic acid aqueous solution, H2SiO3 is used to represent the stable silicic acid aqueous solution in the following examples and the charts in the accompanying drawings, which does not mean to refer to metasilicic acid as a single component.

[0019] To illustrate the application effect of the stable silicic acid aqueous solution in the preparation of the product for treating psoriasis, the present example takes BALB / c mice as the experimental objects to simulate the human psoriasis model as an example for illustration: to explore the effects of different concentrations of the tested drugs on the psoriasis of BALB / c mice, and to provide the basis for the effects of different drugs on the psoriasis of BALB / c mice.

[0020] Imiquimod (IMQ) is a Toll-like receptor (TLR 7 / 8) agonist, and the mouse psoriasis model induced by IMQ produces similar changes to human psoriasis in terms of epidermal thickening, abnormal differentiation of keratinocytes, inflammatory cell infiltration and related inflammatory cytokines. It is generally believed that the lesions of the model are mainly mediated by the IL-23 / IL-17 axis. The IMQ-induced mouse psoriasis-like skin lesions are the most severe on the 6th to 8th day of administration (1 time / 24 h), and then gradually subside, which may be related to the fact that the initiation of skin inflammation is mediated by dendritic cells.

[0021] (I) Experimental materials

[0022] Tested drug: stable silicic acid aqueous solution with concentrations of 0.5%, 1% and 2%; experimental animals: 30 SPF level, male, 6-7 weeks old, weighing 16-20 grams BALB / c mice, provided by Beijing Vantolliva Experimental Animal Technology Co., Ltd. Placed in a SPF level animal room with constant temperature of 22±2℃, day and night each for 12 hours, and caged for feeding.

[0023] (II) Experimental method

[0024] Experimental grouping: 30 BALB / c mice were randomly divided into a control group (Control), a model group (Model), a stable silicic acid aqueous solution low-dose group (0.5%), a stable silicic acid aqueous solution medium-dose group (1%), a stable silicic acid aqueous solution high-dose group (2%), and a positive control group (Calcipotrio), 5 in each group. Adaptively fed for two days.

[0025] Animal skin preparation: the central area of the back of the mouse was shaved, about 2x3cm 2 area. Then, an appropriate amount of depilatory cream was applied, and after 1-2 min, the depilatory cream was scraped off with a scraping tool attached to the depilatory cream, and then wiped twice with a wet cotton ball.

[0026] Mouse modeling: At 10:00 am every day, the normal control group of mice was evenly applied with the cream base to the depilated area. The model group, stable silicic acid aqueous solution low-dose group (0.5%), stable silicic acid aqueous solution medium-dose group (1%), stable silicic acid aqueous solution high-dose group (2%), and positive control group (Calcipotrio) of mice were each applied with 62.5 mg of 5% imiquimod cream, and the other end of the cotton swab was evenly applied. After each mouse completely absorbed the drug, it was transferred back to the mouse cage.

[0027] Test drug treatment: At 16:00 every day, the model group was applied with medical oil-in-water cream base. The stable silicic acid aqueous solution low-dose group (0.5%), stable silicic acid aqueous solution medium-dose group (1%), and stable silicic acid aqueous solution high-dose group (2%) were applied with 80 mg of the corresponding concentration of the test drug, respectively. The positive control group was applied with a small amount of 0.005% calcipotriol ointment. After each mouse completely absorbed the drug, it was transferred back to the mouse cage.

[0028] PASI score: The body weight change of the mice was recorded daily, and the inflammation degree of the skin of the mice was scored by PASI. From the first day of modeling, according to the PASI score standard, the back skin lesions of the mice in each group were scored (erythema score + scale score + hypertrophy score), and the erythema, scale and hypertrophy were scored as 0, 1, 2, 3 and 4 according to the severity of psoriasis, corresponding to no symptoms, mild, moderate, severe and extremely severe. The heavier the skin lesions of the mice, the higher the PASI score. Finally, the three integral values were added to obtain the total PASI score. Specifically, the results of the skin PASI score of the mice are shown in the following table:

[0029] Score 0 1 2 3 4 Thickening Normal Slightly higher than normal skin surface Moderate elevation, round or sloping red edges of plaque Thickening of the skin lesions, obvious elevation Highly thickened skin lesions, very obvious elevation Erythema No erythema Pale red Red Deep red Purple red Scale No scale Part of the lesion surface covered with scales, mainly fine scales Most of the lesion surface is completely or incompletely covered with scales, and the scales are in sheets Almost all the lesion surface scales, the scales are thick and layered All the lesion surface scales, the scales are very thick and layered

[0030] Calculate the spleen index: After the mice were sacrificed on the 7th day, the body weight of the mice was recorded, the spleen was stripped, the surrounding tissue was removed, the excess water was wiped off with filter paper, and the weight of the spleen was recorded. The calculation formula is: spleen index = spleen weight (mg) / mouse weight (g).

[0031] Pathological examination: HE staining was used to observe the pathological changes of the psoriasis-like mice. The skin of the same part of the mouse back was placed in 4% paraformaldehyde for fixation. After 24 hours, dehydration, paraffin embedding, paraffin sectioning and HE staining were performed, and the epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration were observed. The operation steps of HE staining are as follows:

[0032] (1) Dehydration: Place the fixed skin tissue in the dehydration box and sequentially place it in ethanol with decreasing concentration (75% ethanol, 90% ethanol, 90% ethanol, 100% ethanol I, 100% ethanol II, 100% ethanol III) for 1 hour each.

[0033] (2) Transparency: Xylene I, Xylene II, Xylene III each for 45 minutes.

[0034] (3) Wax immersion: Paraffin I, Paraffin II, Paraffin III each for 1 hour.

[0035] (4) Embedding: After the skin tissue is immersed in wax, it is vertically placed in an embedding frame and liquid paraffin is continuously slowly poured into the frame. After the paraffin solidifies, the embedded wax block is taken out and corrected and marked.

[0036] (5) Sectioning: The surface of the wax block is repaired first, and when the tissue is about to be exposed, it is placed into a sectioning machine. After 5 μm sectioning, the specimen is gently placed into warm water at 42°C to flatten, and is taken up with a glass slide and baked at 60°C.

[0037] (6) De-waxing and hydration: The section is placed into an oven at 60°C and baked for 1 hour. The section is immersed into Xylene I and Xylene II each for 15 min, 100% alcohol, 95% alcohol, 90% alcohol, 80% alcohol, 70% alcohol each for 5 min, and then into distilled water for 3 min.

[0038] (7) Staining: Hematoxylin staining solution for 5 min.

[0039] (8) Water washing: The section is washed with running tap water for about 15 min. The color of the section is changed to blue (or it can be placed into alkaline water), but attention should be paid to the fact that the running water should not be too large so as to prevent the section from falling off.

[0040] (9) Differentiation: The section is placed into 1% hydrochloric acid ethanol solution to fade, about 2 seconds. The section is red and the color is light.

[0041] (10) Rinsing: The section is placed into running tap water to restore the blue color.

[0042] (11) Dehydration I: The section is placed into 50% ethanol→70% ethanol→80% ethanol each for 3-5 min.

[0043] (12) Counterstaining: 0.5% eosin ethanol solution for 1 min.

[0044] (13) Dehydration II: The section is placed into 95% ethanol to wash away the excess red color, and then into anhydrous ethanol for 3-5 min. Finally, the excess ethanol is absorbed with a water absorption paper.

[0045] (14) Transparency: The section is placed into Xylene I, II each for 3-5 min.

[0046] (15) Mounting: Neutral balsam is used for mounting.

[0047] (Three) Experimental results

[0048] The experiment used BALB / c mice to explore the effects of different concentrations of test drugs on psoriasis and obtained the following results.

[0049] 1. Effects of different concentrations of test drugs on psoriasis mouse skin lesions

[0050] During modeling, the general condition of mice in each group was acceptable, but after applying calcipotriol ointment in the positive control group, although the degree of scale coverage was reduced compared to the model group, symptoms of skin redness, weight loss, and poor spirits appeared, and recovered after drug treatment was suspended on the fourth day. In addition, the skin of the control group mice was in normal condition; the skin of the model group mice began to show dryness and peeling on the third day, gradually aggravated with thickening of scales, accompanied by skin lesion elevation and redness, and some scales showed signs of shedding on the seventh day. The skin of the drug treatment groups was dry and wrinkled, accompanied by mild local scale-like lesions. Among them, the 0.5% stable silicic acid aqueous solution group and the 1% stable silicic acid aqueous solution group had deep red lesions and rarely had skin scales; the 2% stable silicic acid aqueous solution and calcipotriol treatment groups had obvious skin dryness and wrinkles, accompanied by partial skin lesion scales, as shown in the photographs of Figure 1 .

[0051] The results of the PASI score table are shown in Figure 2 . According to the PASI score, except for the negative control group, the experimental and positive control groups had obvious damage starting on the third day, the degree of skin lesions peaked on the sixth day, and the skin lesions gradually decreased after the sixth day, with a decrease in the PASI score of each group on the seventh day, among which the 0.5% stable silicic acid aqueous solution group and the 1% stable silicic acid aqueous solution group had significantly reduced skin lesions.

[0052] 2. Effects of different concentrations of test drugs on the spleen index of psoriasis mice

[0053] As shown in Figure 3 and Figure 4 , compared with the control group, the spleen index of the model group was significantly increased, with a statistically significant difference (p<0.01), and the spleen index of the 0.5% stable silicic acid aqueous solution group, the 1% stable silicic acid aqueous solution group, the 2% stable silicic acid aqueous solution group, and the positive control group was lower than that of the model group, with a statistically significant difference (p<0.05), indicating that the stable silicic acid aqueous solution drug treatment group was sufficient to reduce the spleen index.

[0054] 3. Effects of different concentrations of test drugs on the histopathology of psoriasis mouse skin lesions

[0055] As shown in Figure 5As shown, compared with the control group, the epidermis of the skin tissue of the model group mice was significantly thickened, hyperkeratosis with parakeratosis, and inflammatory cell infiltration basically consistent with psoriasis-like changes. Compared with the model group, the epidermal thickness of the stable silicic acid aqueous solution solution treatment group was significantly reduced, and local vascular dilation and inflammatory cell infiltration were also reduced, among which the hyperkeratosis and acanthosis of the 1% stable silicic acid aqueous solution solution treatment group were significantly improved; the inflammatory cell infiltration of the positive drug treatment group was reduced, and the specific see Figure 4 .

[0056] The present application verifies the effect of different concentrations of the test drug on the psoriasis mouse model through the above mouse animal experiment. The experimental results show that different concentrations of stable silicic acid aqueous solution can relieve the psoriasis mouse back lesions induced by imiquimod, reduce the erythema, scales and thickness of the mouse back lesions, reduce the spleen index, and improve the pathological structure characteristics, thereby verifying the efficacy and safety of stable silicic acid aqueous solution in treating psoriasis.

[0057] Further, when used externally, the stable silicic acid aqueous solution is dispersed as an active ingredient in an ointment base to obtain a more suitable use mode.

[0058] Further, the present application provides a product for treating psoriasis, the active ingredient of which is stable silicic acid aqueous solution with a mass concentration of 0.5% to 2%, and the product is a medical device or a drug.

[0059] The stable silicic acid aqueous solution of the present application can treat psoriasis as an active ingredient at a mass concentration of 0.5% to 2%. At the same time, the raw material cost of stable silicic acid aqueous solution is low, and it is environmentally friendly and safe, which can be used as a good efficacy and safe alternative choice for treating psoriasis.

[0060] Finally, it should be noted that: the above examples are only used to illustrate the technical solutions of the present application and not to limit them; although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the specific embodiments of the present application can be modified or some technical features can be replaced by equivalent ones; without departing from the spirit of the technical solutions of the present application, they should be covered in the technical solution range of the present application.

Claims

1. The application of a stable silica aqueous solution in the preparation of products for treating psoriasis, wherein, The mass concentration of the stabilized silicic acid aqueous solution is between 0.5% and 2%.

2. The application according to claim 1, characterized in that: When used topically, the stabilized silica aqueous solution is dispersed as an active ingredient in the ointment base.

3. A product characterized in that, The product is used to treat psoriasis. The active ingredient of the product is a stable silicic acid aqueous solution with a mass concentration of 0.5% to 2%. The product is a medical device or a drug.

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