CN113509457B

CN113509457B - Application of sanshool in preparation of medicine for treating eczema

Info

Publication number: CN113509457B
Application number: CN202111040509.5A
Authority: CN
Inventors: 蒋献; 齐锦心
Original assignee: Sichuan Shengjia Technology Co ltd
Current assignee: Sichuan Shengjia Technology Co ltd
Priority date: 2020-09-07
Filing date: 2021-09-06
Publication date: 2023-03-21
Anticipated expiration: 2041-09-06
Also published as: CN113509457A

Abstract

The invention provides application of sanshool in preparing a medicament for treating eczema. The sanshool can effectively improve the infiltrative hypertrophy caused by the skin damage of the eczema so as to further cause the thickening of the cortex, and reduce the contents of mast cells and IgE. The medicine prepared by taking sanshool as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients can treat eczema, has small toxic and side effects, and provides a new choice for clinic.

Description

Application of sanshool in preparation of medicine for treating eczema

Technical Field

The invention belongs to the field of biological medicines, and particularly relates to application of sanshool in preparation of a medicine for treating eczema.

Background

Eczema is a common clinical allergic inflammatory dermatosis, has complex etiology, is generally considered to be related to allergy, clinically has main skin damage such as pimple, blister, exudation, erosion and pruritus, and has the characteristics of severe pruritus, polymorphic lesion, repeated attack, lingering, difficult healing and the like; the skin lesion of the patient shows symptoms of infiltrative hypertrophy, and the number of mast cells in the body is greatly increased. At present, H1 receptor antagonists, glucocorticoids, immunomodulators, antibacterial drugs and the like are mainly used for treatment in clinic, for example, some clinical studies test a strategy related to blocking allergen-specific immunoglobulin E (IgE) which is generated by the immune system when the immune system is used for dealing with allergens, allergic patients can generate IgE under the stimulation of environmental allergens such as pollen, dust mites and the like, then the IgE can be combined with high-affinity receptors on mast cells of skin resident cells, the degranulation of the mast cells is rapidly induced, itch mediators such as histamine and the like are released, and then sensory neurons are activated, and neuroinflammation and itch are caused. It is now even thought that Mast cells are the leading culprit in the development of eczema (Tomoaki Ando, toshiaki Kawakami. Et al. Clinical Role for Mass Cell Stat5Activity in Skin infection [ J ]. Cell Reports,2014,6 (2): in). However, although the existing clinical drugs have obvious short-term curative effect, adverse reactions such as acne-like rash, skin atrophy, telangiectasia, pigmentation, hormone-dependent dermatitis, lethargy, dry mouth, hypodynamia, dizziness, nausea and the like can occur, and the drugs are easy to relapse after stopping taking the drugs, and even further worsen. Therefore, it is of great significance to explore effective methods for treating eczema.

The pericarpium Zanthoxyli is pericarp of plant of Zanthoxylum of Rutaceae (Rutaceae), and has effects of warming spleen and stomach for dispelling cold, eliminating dampness, relieving pain, killing parasite, treating food stagnation, abdominal psychroalgia, toothache, pruritus vulvae, sore, and scabies. The amide substances are the most characteristic alkaloid in the pepper, are the numb taste sources of the pepper, are separated and identified for more than 50 at present, and are represented by sanshool. In recent years, the sanshool has been found to have a wide range of biological effects, including promoting gastric motility, anesthesia and analgesia, expelling parasites, resisting tumors, resisting platelet aggregation and the like. However, the treatment effect of sanshool on eczema is not reported at present.

Disclosure of Invention

The invention aims to provide a new application of sanshool.

The invention provides application of sanshool in preparing a medicine for treating eczema.

Further, the sanshool is one or more of hydroxy-alpha-sanshool, hydroxy-beta-sanshool, hydroxy-gamma-sanshool, hydroxy-delta-sanshool, hydroxy-epsilon-sanshool, alpha-sanshool, beta-sanshool, gamma-sanshool, delta-sanshool, and epsilon-sanshool.

Further, the sanshool is hydroxy- α -sanshool, and preferably, the purity of the hydroxy- α -sanshool is not less than 96%.

Furthermore, the medicine is used for treating skin pleomorphic skin lesions.

Further, the above-mentioned drug is a drug for improving the thickening of the cortex.

Further, the above-mentioned drug is a drug for improving the skin-infiltrating hypertrophy.

Further, the above-mentioned drug is a drug for reducing the number of mast cells.

Further, the above-mentioned drug is a drug for reducing allergen-specific immunoglobulin E.

The invention also provides a medicine for treating eczema, which is a preparation prepared by taking sanshool as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.

Further, the content of sanshool in the preparation is 1-5%; preferably, the sanshool is one or more of hydroxyl-alpha-sanshool, hydroxyl-beta-sanshool, hydroxyl-gamma-sanshool, hydroxyl-delta-sanshool, hydroxyl-epsilon-sanshool, alpha-sanshool, beta-sanshool, gamma-sanshool, delta-sanshool and epsilon-sanshool; more preferably, the sanshool is hydroxy-alpha-sanshool with purity not less than 96%.

The invention provides a new application of sanshool in preparing a medicine for treating eczema, which proves that sanshool can effectively improve the increase of the cortex caused by the infiltration hypertrophy caused by the skin damage of eczema and reduce the contents of mast cells and IgE. The medicine prepared by taking sanshool as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients can treat eczema, has small toxic and side effects, and provides a new choice for clinic.

It will be apparent that various other modifications, substitutions and alterations can be made in the present invention without departing from the basic technical concept of the invention as described above, according to the common technical knowledge and common practice in the field.

The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.

Drawings

FIG. 1 is a schematic representation of the mouse modeling and dosing procedure of the present invention.

FIG. 2 shows the results of serum IgE levels in mice of each group.

FIG. 3 shows the results of the thickness test of the epidermis of each group of mice.

Fig. 4 is the result of mast cell count in each group of mice.

Detailed Description

The sanshool of the invention is hydroxy-alpha-sanshool, purchased from Kyoto Maidesh science and technology Co., ltd., with a purity of 96%.

The starting materials used in the present invention are, unless otherwise stated, known products, obtained by purchasing commercially available products.

EXAMPLE 1 preparation of drug for treating eczema

The sanshool is used as an active ingredient, vaseline serving as an auxiliary material is added, the mixture is uniformly mixed to prepare a medicine with the mass fraction of 1%, the prepared medicine is stored in a 1ml needle tube for administration, and the medicine is stored in a dark place at 4 ℃.

EXAMPLE 2 preparation of drug for treating eczema

The sanshool is used as an active ingredient, vaseline serving as an auxiliary material is added, the mixture is uniformly mixed to prepare a medicine with the mass fraction of 5%, the prepared medicine is stored in a 1ml needle tube to facilitate administration, and the medicine is stored at 4 ℃ in a dark place.

Experimental example 1 verification of Effect of Zanthoxylin on treatment of eczema

1. The experimental method comprises the following steps:

1.1, animal molding process:

molding was carried out using 2,4-Dinitrochlorobenzene (DNCB) for a total of 28 days. Depilating the skin of the back of the mouse with depilatory cream one day before molding, stimulating the back of the mouse with high concentration 2% DNCB on

days

1 and 4, stimulating the back of the mouse with low concentration 0.5% DNCB three times a week on days 7-27, and administering corresponding treatment in different groups for 14 consecutive days from day 14 in a manner of 0.1 ml/mouse/day, wherein each mouse is massaged for 1 minute for facilitating the uniform distribution of the drug in the skin lesion and promoting absorption. Mice were sacrificed on day 28 (the molding and dosing protocol is shown in figure 1).

The grouping is as follows: (1) Sanshool high concentration treatment group (SH-H, model mouse administered with 5% sanshool-containing drug prepared in example 2); (2) A sanshool low-concentration treatment group (SH-L, a molded mouse is administrated by adopting a medicament containing 1% sanshool prepared in example 1) (3) a glucocorticoid group (Dex, a molded mouse is administrated by adopting vaseline as an auxiliary material to prepare a dexamethasone medicament with the content of 0.1%; (4) Model group (Model, model mouse smearing equivalent vaseline); (5) Normal mouse group (Normal, normal mouse smearing equal amount of vaseline)

1.2, ELISA: collecting whole blood from heart of 28 th rhizoma Gastrodiae drunk mouse, standing for more than 30 min for blood coagulation, centrifuging for 15min at 1000g, packaging serum, and storing at-80 deg.C. Detection was performed using a Sammer fly IgE Mouse Uncoated ELISAKit (Catalog # 88-50460-88).

1.3, pathological section: after the mice are killed on the 28 th day, skin tissues at skin lesions on the backs of the mice are taken and fixed in 10 percent formaldehyde solution overnight, and are washed, dehydrated by gradient ethanol, transparent by dimethylbenzene and embedded by dipping wax; slices of 4 μm thickness were cut using a microtome, and the slices were mounted on glass slides and preheated in an oven at 60 ℃ before staining, and were deparaffinized with xylene before staining.

HE staining: staining hematoxylin for 5 minutes, washing for 2-3 times, differentiating with hydrochloric acid alcohol for 5-7 seconds, washing for 2-3 times, returning ammonia water to blue for 1 minute, washing for 2-3 times, soaking with 75% ethanol for a short time, staining with eosin for 45 seconds, and washing for 2-3 times. And (4) checking the dyeing condition under a mirror, dehydrating for 1 minute by using absolute ethyl alcohol, and sealing after natural drying.

Toluidine blue staining: dyeing with toluidine blue for 10 minutes, washing with water for 2-3 times, inspecting the dyeing condition under a mirror, dehydrating with absolute ethyl alcohol for 1 minute, naturally drying, and sealing.

Drawing and statistics: the HE stained section randomly selects three visual fields for measuring the thickness of the epidermis, and the result is expressed by an average value; toluidine blue stained sections 3 fields of 400X each were randomly selected and mast cells were counted separately and the results are expressed as mean values.

2. The experimental results are as follows:

the results of ELISA for IgE detection after 100-fold dilution of mouse serum (FIG. 2) show that the IgE levels of the mouse serum in the experiment group treated by sanshool are all reduced compared with the model group, and the reduction degree is in direct proportion to the concentration of the sanshool.

Statistical results (fig. 3) of the mice epidermis thickness measured in HE stained pathological section show that the skin thickness of sanshool group is decreased compared with the model group, and the decrease degree is in direct proportion to the concentration of sanshool.

Statistics of mast cell counts (fig. 4) show that the number of mast cells in the epidermis of sanshool group decreased in proportion to sanshool concentration compared to the model group.

The above results indicate that sanshool has excellent effects of improving the increase in mast cell number and IgE level caused by eczema, and can improve the thickening of the skin layer caused by the invasive hypertrophy of the skin damage of eczema.

In the whole administration process, the mice of the sanshool group have no obvious adverse reaction, which indicates that the sanshool does not cause obvious toxic or side effect.

In conclusion, the invention provides an application of sanshool in preparing a medicine for treating eczema. The sanshool can effectively improve the thickening of the cortex caused by the infiltrative hypertrophy caused by the skin damage of the eczema, and reduce the contents of mast cells and IgE. The medicine prepared by taking the sanshool as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients can treat eczema, has small toxic and side effects, and provides a new choice for clinic.

Claims

1. Use of hydroxy-alpha-sanshool as the sole active ingredient in the manufacture of a medicament for the treatment of eczema.

2. The use according to claim 1, wherein the hydroxy- α -sanshool has a purity of not less than 96%.

3. The use of claim 1, wherein the medicament is for treating skin pleomorphic lesions.

4. The use of claim 3, wherein the medicament is for improving cortical thickening.

5. The use of claim 4, wherein the medicament is for improving skin-invasive hypertrophy.

6. Use according to any one of claims 1 to 5, wherein the medicament is for reducing mast cell number.

7. Use according to any one of claims 1 to 5, wherein the medicament is for reducing allergen-specific immunoglobulin E.