Application of succinyl glycan riclin in preparation of medicine for treating atopic dermatitis

Abstract

The invention discloses an application of succinyl glycan riclin in preparation of a medicine for treating atopic dermatitis. Succinyl glycan riclin can significantly improve the skin condition of a DNCB-induced atopic dermatitis mouse model, including reducing the skin inflammatory factor level, improving the skin barrier function and reducing the lymph node quality and the number of lymphocytes, has no abnormal influence on blood routine examination, and has no toxic or side effect. The composition has the advantages of small drug application dosage, low pharmaceutical cost, safety, no side effect, strong drug effect and the like, and has a wide application prospect.

Description

Technical Field

[0001] The present invention belongs to the field of drugs for treating atopic dermatitis, and relates to the application of succinoglycan riclin in the preparation of drugs for treating atopic dermatitis. Background Art

[0002] Atopic dermatitis (AD) is a common chronic, recurrent, inflammatory skin disease, usually related to genetics, abnormal immune function and environmental factors. The main symptoms include skin itching, dryness, redness, desquamation, and even exudation and crusting. In the chronic stage, skin thickening (lichenification) and pigmentation may occur.

[0003] Currently, the methods for treating atopic dermatitis are mainly based on three theories: reducing allergen exposure, using drugs, and ultraviolet therapy. Drug therapies currently include steroids and antihistamine drugs. Among them, steroids such as prednisone are used in the acute attack stage, but long-term use may have side effects. Antihistamine drugs are generally used to relieve itching. However, the above methods have large individual differences in treatment and poor patient compliance, and their safety and effectiveness limit their clinical application. Some anti-inflammatory drugs have also been applied to the treatment of atopic dermatitis, but not all drugs with anti-inflammatory effects are suitable for the treatment of atopic dermatitis. Atopic dermatitis is a complex immune system disease, not only caused by inflammation, but also involves many links such as damage to the skin barrier function and allergic reactions. Therefore, developing new drugs for treating atopic dermatitis and providing more choices for individualized treatment of future atopic dermatitis patients has important practical significance.

[0004] The prior research of the inventors reported succinoglycan riclin and its preparation method, and pointed out that the succinoglycan has anti-tumor activity and anti-inflammatory activity ([1] Y. Yang, X. Sun, Y. Zhao, et al., Anti-tumor activity and immunogenicity of a succinoglycan riclin, Carbohydr. Polym. 2021 Mar 1; 255: 117370. [2] R. Cheng, L. Wang, J. Li., et al., In vitro and in vivo anti-inflammatory activity of a succinoglycan Riclin from Agrobacterium sp. ZCC3656, J. Appl. Microbiol. 2019 Dec; 127(6): 1716 - 1726.). Patent application CN 111286466 A also disclosed the preparation method and anti-inflammatory activity of the succinoglycan riclin. Patent application CN 116327794 A disclosed the application of succinoglycan riclin in the preparation of drugs for the treatment and / or prevention of type 2 diabetes. However, whether succinoglycan riclin has a therapeutic effect on atopic dermatitis has not been reported yet. Summary of the Invention

[0005] The present invention provides an application of succinoglycan riclin in the preparation of drugs for the treatment of atopic dermatitis.

[0006] The structural formula of the succinoglycan riclin described in the present invention is:

[0007]

[0008] R = OCCH 2 CH 2 COOH or H, where n = 1 - 2000.

[0009] The dosage forms of the drugs for the treatment of atopic dermatitis described in the present invention include but are not limited to topical application solutions or creams.

[0010] The administration method of the drugs for the treatment of atopic dermatitis described in the present invention is administration by surface application.

[0011] The drugs for the treatment of atopic dermatitis described in the present invention can be administered to any animal that may develop or has developed atopic dermatitis. These animals include humans and non-human animals, such as pets or livestock, etc.

[0012] The dosage of the drug for treating atopic dermatitis according to the present invention depends on the age, health and weight of the recipient, treatment frequency, etc.

[0013] In the drug for treating atopic dermatitis according to the present invention, the concentration of succinoglycan riclin is 0.01 g / L to 1 g / L, preferably 0.05 g / L.

[0014] Compared with the prior art, the present invention has the following remarkable advantages:

[0015] The present invention discovers for the first time that succinoglycan riclin has the effect of improving the skin of mice with artificial drug-induced atopic dermatitis, can improve the skin condition, can be used as a drug for treating atopic dermatitis, and treats the disease by reducing inflammatory factors at the diseased site. In addition, succinoglycan riclin has the advantages of small drug administration dosage, low pharmaceutical cost, safety without side effects, strong drug effect, etc., and has a wide application prospect. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is a macroscopic picture of the skin of mice with DNCB-induced atopic dermatitis improved by succinoglycan riclin.

[0017] Figure 2 It is the QRT data of the skin of mice in the treatment group and the control group, where IL-5, IL-6, IL-8, IL-13, TNF-α are pro-inflammatory factors; Loricrin is an index for evaluating skin barrier function.

[0018] Figure 3 It is a graph of the lymphocyte count and lymph node mass data of mice in the treatment group and the control group.

[0019] Figure 4 It is a section graph of the epidermal thickness and dermal thickness of the skin of mice in the treatment group and the control group.

[0020] Figure 5 It is a blood routine analysis graph of mice in the treatment group and the control group. DETAILED DESCRIPTION OF THE INVENTION

[0021] Unless otherwise specified, the methods used in the following examples are all methods commonly used in the art. All raw materials used in the following examples are commercially available products unless otherwise specified. Unless otherwise defined, all technical and scientific terms used in the present invention have the meanings commonly understood by those of ordinary skill in the art to which the present invention belongs.

[0022] The succinoglycan riclin in the present invention is prepared by conventional methods known in the art. Specifically, it can be prepared according to the methods taught in R. Cheng, L. Wang, J. Li., et al., J. Appl. Microbiol., 127(6): 1716-1726. (2019) and patent application CN 111286466 A.

[0023] The present invention will be further described in detail below in conjunction with examples and drawings.

[0024] Example 1

[0025] Study on the improvement of atopic dermatitis in mice by succinoglycan riclin

[0026] (1) Establishment of animal model

[0027] Male C57BL / 6 mice (8-10 weeks old) from the Model Animal Research Center of Nanjing University were used in the experiment. All mice were housed under standard conditions with a 12-hour light - 12-hour dark cycle and had free access to food and water. To establish an atopic dermatitis mouse model, after removing the hair on the back of the experimental group mice, 20 g / L of 2,4-dinitrochlorobenzene (DNCB) solution was applied to the ears and back respectively to induce atopic dermatitis. The DNCB solution was prepared by dissolving DNCB in PBS solution.

[0028] (2) Experimental grouping

[0029] Five days after the establishment of the atopic dermatitis model, the mice were randomly divided into 4 groups (5 mice in each group): the CK group, which were normal mice and were smeared with physiological saline every day; the Model group, which were mice with DNCB-induced atopic dermatitis and were smeared with 5 g / L of DNCB solution and physiological saline every day; the LRO group, which were mice treated with low-concentration riclin emulsion and were smeared with 0.01 g / L of riclin emulsion and physiological saline every day; the HRO group, which were mice treated with high-concentration riclin emulsion and were smeared with 0.05 g / L of riclin emulsion and physiological saline every day. The skin of the mice was recorded every day. The riclin emulsion was prepared by using the PBS solution of succinoglycan riclin and olive oil as emulsion components and stearic acid as an emulsifier, and the emulsion was obtained after emulsification treatment.

[0030] (3) Skin condition recording

[0031] The skin of the mice was photographed at the same time every day to record the skin condition.

[0032] (4) Determination of skin inflammatory factors

[0033] On the seventh day, the mice were sacrificed, and tissues and blood were taken for analysis. The levels of IL-5, IL-6, IL-8, IL-13, TNF-α, and Loricrin in the skin of mice in different groups were measured.

[0034] (5) Determination of lymphocyte count and lymph node mass

[0035] After sacrificing the mice, the lymphoid tissues were obtained, the mass of the lymph nodes was weighed, and the lymphocyte count was determined.

[0036] (6) Histopathological analysis of mouse skin tissue

[0037] The collected skin was stained with H&E.

[0038] (7) Routine blood analysis of mice

[0039] Routine blood tests were performed on the collected blood.

[0040] (8) Data analysis

[0041] One-way / Two-way ANOVA statistical methods were used for statistical analysis of comparisons between multiple groups. P < 0.05 was considered to have a significant effect.

[0042] (9) Result analysis

[0043] As Figure 1 shown, the experimental results showed that compared with the Model group, after treatment with riclin, the skin of the mice was significantly improved.

[0044] As Figure 2 shown, the experimental results showed that compared with the Model group, after treatment with riclin, the inflammatory factors in the skin of the mice were significantly decreased and the skin barrier was more complete.

[0045] As Figure 3 shown, the experimental results showed that compared with the Model group, after treatment with riclin, the mass of the lymph nodes and the lymphocyte count of the mice were significantly lower than those of the model group.

[0046] As Figure 4 shown, the experimental results showed that compared with the Model group, after treatment with riclin, the increase in the thickness of the epidermis and dermis of the mice decreased. The black line in the figure is the epidermis and the gray line is the dermis. These results indicate that riclin treatment improved the related pathological characteristics of atopic dermatitis mice.

[0047] As Figure 5As shown, the experimental results indicate that compared with the Model group, after treatment with riclin, there were no abnormalities in the blood routine of the mice. These results suggest that riclin treatment improved the relevant pathological characteristics of atopic dermatitis mice and was non-toxic and harmless. Riclin protected the skin of the mice.

Claims

1. The use of succinoglycan riclin in the preparation of a drug for treating atopic dermatitis, characterized in that: The structural formula of the succinoglycan riclin is: ， R = OCCH2CH2COOH or H, where n = 1~2000.

2. The use according to claim 1, characterized in that: Drugs for treating atopic dermatitis are available in the form of topical solutions or creams.

3. The use according to claim 1, characterized in that: The drug for treating atopic dermatitis is administered by topical application.

4. The use according to claim 1, characterized in that: The subject of administration of the drug for treating atopic dermatitis is a human or non-human animal who may develop or has developed atopic dermatitis.

5. The use according to claim 1, characterized in that: In drugs for the treatment of atopic dermatitis, the concentration of succinoglycan riclin is 0.01 g / L ~1 g / L.

6. The use according to claim 1, characterized in that: In drugs for the treatment of atopic dermatitis, the concentration of succinoglycan riclin is 0.05 g / L.

Images