阅读说明：本技术 一种异牡荆素的应用 (Application of isovitexin ) 是由 李艳平 汪伟光 何红平 李婷 邹秋萍 于 2020-05-13 设计创作，主要内容包括：本发明公开了一种异牡荆素的应用,所述的异牡荆素的应用为所述的异牡荆素在制备抗溃疡性结肠炎药物中的应用。本发明实验显示异牡荆素能有效改善溃疡性结肠炎小鼠的一般状态、显著抑制DSS诱导的小鼠结肠变短、改善结肠组织病理学、降低髓过氧化物酶、显著减轻炎症反应、降低血清中促炎因子的表达,促进抑炎因子的生成,进而发挥抗炎作用。(The invention discloses an application of isovitexin, which is an application of the isovitexin in preparing an anti-ulcerative colitis medicament. Experiments show that the isovitexin can effectively improve the general state of an ulcerative colitis mouse, obviously inhibit the shortening of the colon of the mouse induced by DSS, improve the histopathology of the colon, reduce myeloperoxidase, obviously relieve inflammatory reaction, reduce the expression of proinflammatory factors in serum, promote the generation of the inflammation-inhibiting factors and further play an anti-inflammatory role.)

1. The application of isovitexin is characterized in that the isovitexin is applied to the preparation of anti-ulcerative colitis medicaments.

2. The use of isovitexin of claim 1, wherein said effective amount of isovitexin is 100 mg/kg.

3. The use of isovitexin of claim 1, wherein said isovitexin is combined with other active ingredients as a main active ingredient into a pharmaceutical composition for treating ulcerative colitis.

4. The use of isovitexin of claim 3, wherein the pharmaceutical composition for treating ulcerative colitis can be formulated into tablets, pills, dripping pills, capsules, soft capsules, granules, powders, oral liquids, injections or emulsions with pharmaceutically acceptable carriers.

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to application of isovitexin.

Background

Ulcerative Colitis (UC) is a chronic nonspecific inflammatory disease of the rectum and colon whose etiology is not well understood. Lesions are mainly confined to the large intestinal mucosa and submucosa. The clinical manifestations are diarrhea, mucopurulent bloody stool and abdominal pain. The disease condition is mild or severe, and usually presents a chronic course of repeated attack. This disease can occur at any age, most commonly between 20 and 40 years of age, and is also seen in children or the elderly. The incidence rates of male and female have no obvious difference. The disease is rare in our country compared with Europe and America, and the disease condition is generally mild, but in recent years, the disease rate is obviously increased, and severe cases are frequently reported. The ulcerative colitis has complex etiology, multiple pathogenic links, high curing difficulty, repeated attack and close relation with the attack of colon cancer. The disease was first described by Willks and Moxon in 1875 and was formally named by the World Health Organization (WHO) International organization Committee of the medical science organization in 1973, which was listed as one of the modern refractory diseases by the world health organization. Thus, effective prevention, discovery and early treatment of inflammatory bowel disease are of great social significance.

The pathogenic factors and pathogenesis of UC are not well defined. The pathogenesis of the disease is considered to be complex at present, and the disease is related to a plurality of factors, such as genetic factors, mental factors, immune factors (cytokines, leptin, adiponectin, immune cells and the like), infection factors (bacteria), environmental factors (dietary habits, living habits and the like) and inflammation mediators and the like. The conventional medicines currently used for treating UC are mainly 5-aminosalicylic acid, corticosteroids, immunosuppressants, antibiotics, biological agents (anti-TNF-alpha antibodies) and the like. The treatment mainly aims at relieving symptoms, and has the problems of easy relapse after medicine withdrawal, increased drug resistance, more adverse reactions and the like. For example, the sulfasalazine carrier has certain toxicity on partial sulfanilamide, and obvious adverse reaction can occur after 15 to 45 percent of patients take the sulfasalazine carrier; glucocorticoid has strong anti-inflammatory effect, but can cause the body to have sugar, lipid and protein metabolism disorder and have complications such as osteoporosis and even femoral head necrosis after long-term application; research indicates that long-time taking of the immunosuppressant may be accompanied by adverse reactions such as infection, pancreatitis, headache, fever, liver injury and the like, and even cause tumor formation. Certain antibiotics, such as the quinolone ciprofloxacin, penicillins, non-aminoglycoside rifaximin are also used in the treatment of UC. However, the use of antibiotics does not prevent the recurrence of UC and can lead to the development of severe bacterial resistance. The chronic inflammation state of UC is likely to be converted into colorectal cancer, so that the search of a medicament with definite curative effect, small toxic and side effect and low price is a hot spot explored in recent years.

Isovitexin (IV), also known as isovitexin, or 6-C-glucoapigenin, is a yellow powder; the molecular formula is as follows: c₂₁H₂₂O₁₀(ii) a Molecular weight: 432; belongs to the flavonoid active substance of the carbon glycoside, and is widely existed in roots, stems, leaves, barks, fruits and seeds of dozens of plants in the nature. Such as Vitex agnus-castus (Vitex agnus-castus) of VerbenaceaeVitex littoralisA. cunn.) leaves, Gleditsia sinensis (Lam.) Ohwi of LeguminosaeGleditsia sinensisLam.) and Lespedeza cuneataLespedeza cuneataDon's leaves, and mung beans: (Vigna radiateL.) and the like. A large number of studies have shown that isovitexin has a variety of pharmacological activities, including lowering blood glucose, inhibiting bacteria, regulating memory, inhibiting growth of microorganisms, and reducing blood glucoseαGlucosidase, blood pressure lowering and antioxidant effects. However, the application of the isovitexin in ulcerative colitis is not reported.

Disclosure of Invention

The invention aims to provide application of isovitexin.

The purpose of the invention is realized by the application of the isovitexin in preparing the anti-ulcerative colitis medicine.

Experiments show that the isovitexin can effectively improve the general state of an ulcerative colitis mouse, obviously inhibit the shortening of the colon of the mouse induced by DSS, improve the histopathology of the colon, reduce myeloperoxidase, obviously relieve inflammatory reaction, reduce the expression of proinflammatory factors in serum, promote the generation of the inflammation-inhibiting factors and further play an anti-inflammatory role. Experiments prove that the isovitexin has a protective effect on DSS-induced ulcerative colitis. On an animal model, the result shows that the isovitexin has obvious curative effect on mice with DSS-induced ulcerative colitis. The preparation method comprises the steps of effectively improving the general state of an ulcerative colitis mouse, obviously inhibiting DSS-induced shortening of the mouse colon, improving colon histopathology, reducing myeloperoxidase, obviously relieving inflammatory reaction, reducing the expression of proinflammatory factors in serum, promoting the generation of the inflammation-inhibiting factors and further playing an anti-inflammatory role. The isovitexin can be used for preparing medicines for preventing and treating ulcerative colitis.

The isovitexin has the advantages of quick action, exact curative effect and good drug effect in treating ulcerative colitis.

In another aspect, the present invention provides a pharmaceutical composition comprising isovitexin or a solvate thereof, and a pharmaceutically acceptable carrier for use in the treatment of ulcerative colitis.

The pharmaceutical composition is preferably in the form of tablet, pill, dripping pill, capsule, granule, powder, injection, oral liquid or emulsion.

The above pharmaceutical composition, more preferably, is a tablet, a dripping pill, a soft capsule, a hard capsule or an emulsion.

In still another aspect, the present invention provides a method for preparing a pharmaceutical composition comprising isovitexin, characterized in that isovitexin or a pharmaceutically acceptable solvate thereof is prepared in admixture with a pharmaceutically acceptable carrier, said pharmaceutical composition being for the treatment of ulcerative colitis.

The invention discloses an anti-ulcerative colitis effect of isovitexin, namely the isovitexin can be used for preparing anti-ulcerative colitis medicines and has good drug effect.

The term "pharmaceutical composition" denotes a mixture comprising a therapeutically effective amount of one or more of the active ingredients and pharmaceutically acceptable solvates thereof, together with other pharmaceutically acceptable carriers. The compounds are formulated into pharmaceutical compositions for more convenient administration to a subject in need thereof.

The pharmaceutical composition can be tablets, pills, capsules, granules, powder, suppositories, powder, paste, patches, injection, solution, suspension, spray, lotion, drops and liniment.

The pharmaceutically acceptable carrier of the present invention is a pharmaceutically acceptable component or medium, including but not limited to solvents, excipients, diluents, adjuvants, fillers, etc. Common pharmaceutically acceptable carriers include physiological saline, buffers, sugars, gelatin, starch, ringer's solution, cellulose, and the like.

All methods described herein can be performed in any suitable order, as understood by those skilled in the art, unless otherwise indicated herein or otherwise clearly contradicted by context.

Drawings

FIG. 1 is a graph of the body weight change trend of mice with casticin versus DSS-induced ulcerative colitis;

FIG. 2 is a graph of the DAI score of mice with isovitexin versus DSS-induced ulcerative colitis;

FIG. 3 is a representative colon-derived image of a mouse with ulcerative colitis induced by DSS using isovitexin;

FIG. 4 is a bar graph of colon length differences of isovitexin versus DSS-induced ulcerative colitis mice;

FIG. 5 is a graph of H & E colon staining of mice with DSS-induced ulcerative colitis by isovitexin;

FIG. 6 is a graph of the effect of isovitexin on Myeloperoxidase (MPO) in colon tissue of DSS-induced ulcerative colitis mice;

FIG. 7 shows the combination of isovitexin with TNF-beta, a serum inflammatory factor in DSS-induced ulcerative colitis miceαA schematic of the effect of the levels;

FIG. 8 shows the serum inflammatory factor IL-1 of mice with DSS-induced ulcerative colitis induced by isovitexinβA schematic of the effect of the levels;

FIG. 9 is a graph showing the effect of isovitexin on the levels of serum inflammatory factor IL-6 in mice with DSS-induced ulcerative colitis;

control is a Control group; DSS is a model group; DSS +5-ASA was the 5-aminosalicylic acid positive drug group (500 mg/kg); IV is isovitexin drug group (100 mg/kg); n = 10; note: # P < 0.05 vs control group; p < 0.05 vs model group.

Detailed Description

The present invention is further illustrated by the following examples and the accompanying drawings, but the present invention is not limited thereto in any way, and any modifications or alterations based on the teaching of the present invention are within the scope of the present invention.

The application of the isovitexin is the application of the isovitexin in preparing the anti-ulcerative colitis medicine.

The effective amount of the isovitexin is 100 mg/kg.

The pharmaceutical composition is a pharmaceutical composition for treating ulcerative colitis, which is prepared by combining the isovitexin as a main active ingredient and other active ingredients.

The pharmaceutical composition for treating ulcerative colitis can be added with pharmaceutically acceptable carriers to prepare tablets, pills, dripping pills, capsules, soft capsules, granules, powder, oral liquid, injection or emulsion.

The invention is further illustrated by the following specific examples: