阅读说明：本技术 黄酮c-苷类化合物的用途 (Application of flavone C-glycoside compounds ) 是由 陈永轩 翁庆丰 傅耀贤 吴秀娜 杨榕 罗联忠 于 2020-05-18 设计创作，主要内容包括：本发明公开了黄酮C-苷类化合物的用途,具体为黄酮C-苷类化合物apigenin 6-C-[arabinopyranosyl-(1”’→2”)-glucopyranoside]-7-O-Glucopyranoside以及包括该黄酮C-苷类化合物apigenin 6-C-[arabinopyranosyl-(1”’→2”)-glucopyranoside]-7-O-Glucopyranoside的组合物在制备降血糖的药物、制备辅助降血糖的保健食品中的用途。本发明的黄酮C-苷类化合物apigenin 6-C-[arabinopyranosyl-(1”’→2”)-glucopyranoside]-7-O-Glucopyranoside由皱瘤海鞘经正丁醇提取纯化而得,其降血糖功效近似于胰岛素及二甲双胍,可用于降血糖及糖尿病的控制,且可口服施用,避免了注射用的胰岛素会因诸多因素影响疗效及因同一区域内注射次数过于频繁而引起注射部位皮下组织的伤害。(The invention discloses an application of a flavone C-glycoside compound, in particular to an application of a flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1 '→ 2 ") -Glucopyranoside ] -7-O-Glucopyranoside and a composition containing the flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2") -Glucopyranoside ] -7-O-Glucopyranoside in the preparation of a hypoglycemic medicament and a hypoglycemic health food. The flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -Glucopyranoside ] -7-O-Glucopyranoside is obtained by extracting and purifying ascidian plicata nodules by n-butyl alcohol, has the blood sugar reducing effect similar to that of insulin and metformin, can be used for controlling blood sugar reduction and diabetes, can be orally administered, and avoids the damage of subcutaneous tissues of injection parts caused by the influence of a plurality of factors on the curative effect and the over-frequent injection times in the same region by the insulin for injection.)

1. Use of flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside in preparing medicament for lowering blood sugar.

2. Use of a composition comprising flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside in the preparation of a medicament for lowering blood glucose.

3. Use of flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside in preparing health food for assisting blood sugar reduction.

4. An application of a composition containing flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1 '→ 2') -glucopyranoside ] -7-O-glucopyranoside in preparing health food for assisting blood sugar reduction.

5. Use according to claim 2 or 4, characterized in that: the composition is an n-butanol extract of ascidian rupestris.

6. Use according to any one of claims 1 to 4, characterized in that: the flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside is obtained by leaching and purifying ascidian rupestris frena with n-butanol.

7. Use according to any one of claims 1 to 4, characterized in that: the effective amount of the flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside for reducing blood sugar is 9-90 mg/day.

8. Use according to any one of claims 1 to 4, characterized in that: the medicine is an oral preparation.

9. Use according to claim 8, characterized in that: the oral preparation is in the form of pill, capsule, tablet, lozenge, granule, powder, mixture, syrup, drop or emulsion.

10. Use according to any one of claims 1 to 4, characterized in that: the medicine also comprises at least one pharmaceutically acceptable auxiliary material or carrier.

Technical Field

The invention belongs to the technical field of natural extracts, and particularly relates to a flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside and application of a composition thereof in preparation of a hypoglycemic medicament and a hypoglycemic health food.

Background

The current treatment for diabetes can be divided into three parts: regular exercise, diet control and medication. The medicinal treatment of diabetes is classified into oral hypoglycemic agent or insulin injection. If the blood sugar is still poorly controlled after oral hypoglycemic agent treatment, insulin injection therapy may be required instead. However, due to the difference of the action mechanism of the medicines, the taking time is also different: firstly, the medicine is taken 30min before meal, taken immediately before meal or taken with meal, and the medicine has the function of stimulating insulin secretion; secondly, the drugs taken after meals are used for improving insulin resistance and reducing glucose output of the liver, but the effect is mostly in the gastrointestinal tract, so that the side effect of gastrointestinal discomfort can be avoided when patients take the drugs after meals. Among the side effects of hypoglycemic drugs, hypoglycemia is generally the most common, and is particularly more likely to occur when patients take drugs without matching with eating time or engage in activities that consume blood sugar without eating; secondly, gastrointestinal discomfort; in addition, hepatotoxicity may be caused.

The insulin for injection is the same as or almost the same as the insulin generated in a human body, is widely used at present, can achieve the most effective treatment on diabetes, and reduces the problems possibly caused by poor blood sugar control, such as the pathological changes of eyes, kidneys and peripheral nerves. However, the injection position, injection depth, movement and dosage all affect the absorption of insulin. In order to obtain stable insulin absorption and action, attention must be paid to the fact that the injection frequency in the same injection region is not too frequent, so that the injection is not suitable to be injected into the same point every time, the injection point and the last injection point are kept at the distance of three fingers, so that the stable absorption of the insulin can be ensured, the delayed absorption is avoided, and the injury of subcutaneous tissues of the injection region caused by the too frequent injection frequency in the same region is avoided.

Halocynthia reniformis (Styela plicata), also known as Sea Squirts, is a urospora species of the Ascidiacea, phylum urosum. Many mature organisms of ascidians belong to benthic filter feeders, and part of species can be economically eaten, and the organisms are rich in colloid, taurine, polyunsaturated fatty acid, folic acid, pantothenic acid and cholesterol and have certain nutritional value. The medical care efficacy of the ecthyma animals is gradually concerned in recent years, but the application of the ecthyma animals in blood sugar reduction is not reported by scientific research results, and no corresponding products are available in the market.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides application of a flavone C-glycoside compound, in particular application of the flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside in preparing a hypoglycemic medicament or preparing a hypoglycemic health food.

One of the technical schemes adopted by the invention for solving the technical problems is as follows:

use of flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside in preparing medicament for lowering blood sugar.

The second technical scheme adopted by the invention for solving the technical problems is as follows:

use of a composition comprising flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside in the preparation of a medicament for lowering blood glucose.

The third technical scheme adopted by the invention for solving the technical problems is as follows:

use of flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside in preparing health food for assisting blood sugar reduction.

The fourth technical scheme adopted by the invention for solving the technical problems is as follows:

an application of a composition containing flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1 '→ 2') -glucopyranoside ] -7-O-glucopyranoside in preparing health food for assisting blood sugar reduction.

The flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside in the invention is derived from the extract of ascidian abomasum, but not limited thereto. The present invention relates to a mixture obtained by crushing all or part of the body tissue of Echinacea purpurea and extracting the crushed material with a solvent. The extract comprises crude extract (raw extract) and refined extract (refined extract) or pure compound (pure compound) after treatment and purification. More specifically, the crude extract is the product of a simple extraction in which the selected ascidians are at least partially contacted with at least one extraction solvent, optionally followed by one or more separation and/or purification treatments to obtain a refined extract or a pure compound.

The flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside is used as an active ingredient, and is in a gas, liquid, powder or solid state. In the invention, the flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside is obtained by leaching and purifying all or part of tissues of the body of the ascidian rupestris rugosa by a solvent, wherein the solvent is preferably n-butyl alcohol, and the purification method is high-speed counter-current chromatography and high performance liquid chromatography.

The flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside of the present invention may be in a liquid form (such as a solution, a concentrate or a distillate) or a solid matter (such as a paste, a granule or a dried powder) from which a solvent is removed, and the solid matter may be further dissolved in a solvent such as water, an alcohol (such as ethanol), or an oil, and an oil such as, but not limited to, soybean oil or other edible oil may be used.

The composition of the present invention refers to a mixture or compound consisting of two or more substances, and contains the flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside of the present invention as an active ingredient, whether it is a gas, a liquid, a powder or a solid. In one embodiment, the composition comprising flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1 '→ 2') -glucopyranoside ] -7-O-glucopyranoside of the present invention is an n-butanol extract of ascidian rufii, for example, a crude n-butanol extract of ascidian rufii or a purified n-butanol extract of the crude n-butanol extract after one or more separation and/or purification treatments, in which case the n-butanol extract of ascidian rufii can be directly used for preparing an oral medicament.

Preferably, in the composition of the present invention, in addition to the flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside, insulin, metformin, etc. may be included to obtain a synergistic hypoglycemic effect.

In the invention, the effective amount of the flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1 '→ 2') -glucopyranoside ] -7-O-glucopyranoside for reducing blood sugar is 1-10 mg/kg of B.W./day ICR mice, and the adult equivalent dose is 9-90 mg/day.

An effective amount (effective amount) as used herein refers to an amount of a pharmaceutical composition sufficient to produce the desired therapeutic result, wherein the exact nature of the result will vary depending on the particular disease being treated. The specific effective amount will depend upon a variety of factors such as the particular condition being treated, the physiological condition of the patient (e.g., the patient's weight, age or sex), the type of animal being treated, the duration of treatment, the mode of administration, the nature of the current therapy (if any), and the specific formulation and structure of the compound or derivative thereof being used. An effective amount also refers to a compound or composition whose therapeutic benefit exceeds its toxic or deleterious effects. For example, an effective amount may be expressed as the total weight of the drug (e.g., in grams, milligrams, or micrograms) or as the ratio of the weight of the drug to the body weight in milligrams per kilogram (mg/kg).

The flavone C-glycoside compound apigenin6-C- [ arabidopsis- (1 '→ 2 ") -glucopyranoside ] -7-O-glucopyranoside of the present invention or the composition comprising the flavone C-glycoside compound apigenin6-C- [ arabidopsis- (1' → 2") -glucopyranoside ] -7-O-glucopyranoside can be prepared into oral pharmaceutical formulations, and the specific dosage form of the orally administered drug can be capsules, pills (such as sugar-coated pills and the like), tablets, lozenges (buccal troches), powders, granules, mixtures (oral liquids), or in the form of solutions or suspensions in aqueous or non-aqueous liquids, such as drops, or in the form of oil-in-water or liquid emulsions, such as emulsions, or water-in-oil liquid forms.

In solid dosage forms (capsules, pills, tablets, troches, powders, granules and other oral dosage forms) of drugs for oral administration, the drugs of the present invention can be used for applications such as the production of health foods, pharmaceuticals, industrial materials, and the like.

The health food of the invention is suitable for specific people to eat, has the function of regulating the organism, does not aim at treating diseases, and does not produce any acute, subacute or chronic harm to human bodies. The health food of the present invention includes, for example, nutritional supplementary food, health food, functional food, food for the elderly, and the like.

In the present invention, the medicament may further comprise at least one pharmaceutically acceptable adjuvant or carrier. The auxiliary materials include but are not limited to diluents, solvents, excipients, absorbents, wetting agents, adhesives, disintegrants, lubricants, solubilizers, emulsifiers, suspending agents, surfactants, film forming agents, propellants, antioxidants, flavoring agents, fragrances, bactericides, preservatives and the like; the carrier is a system which can carry a compound, has the functions of changing the mode of the compound entering a human body and the distribution of the compound in the body, controlling the release speed to achieve controlled release or sustained release, targeting delivery to target organs and the like, and comprises but is not limited to liposome, microsphere, microcapsule, solid dispersion, micelle, microemulsion, gel, sustained release carrier, controlled release carrier, targeting carrier, nanoparticle material and the like.

The equipment, reagents, processes, parameters and the like related to the invention are conventional equipment, reagents, processes, parameters and the like except for special description, and no embodiment is needed.

All ranges recited herein include all point values within the range.

Compared with the background technology, the technical scheme has the following advantages:

1. the invention provides application of flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1 '→ 2 ") -glucopyranoside ] -7-O-glucopyranoside and a composition thereof in preparing medicines and health-care foods for reducing blood sugar and controlling diabetes, wherein the effect of reducing blood sugar is similar to that of most effective hypoglycemic medicines such as insulin and metformin which are widely used in the prior art, and the flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2") -glucopyranoside ] -7-O-glucopyranoside has the liver protection function.

2. The flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside can be orally administered, so that the damage of subcutaneous tissues of an injection part caused by the influence of a plurality of factors on the curative effect and the over-frequent injection frequency in the same area caused by the insulin for injection is avoided.

3. The extract of the invention is derived from the ascidian yezoensis, the raw materials are easy to obtain, and the development of the medicine can fully recycle a large amount of culture by-products ascidian yezoensis at present, thereby avoiding resource waste.

Drawings

The invention is further illustrated by the following figures and examples.

FIG. 1 is a structural formula of flavonoid C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1 '→ 2') -glucopyranoside ] -7-O-glucopyranoside compound of the present invention.

FIG. 2 shows the flavone C-glycoside compound apigenin6-C- [ arabidopyronyl- (1 '→ 2') -glucop of the present inventionyranoside]Process for producing (E) -7-O-glucopyranoside compound¹And (4) an H spectrum.

FIG. 3 shows apigenin6-C- [ arabinopyranosyl- (1 '→ 2') -glucopyranoside, a flavone C-glycoside compound of the present invention]Process for producing (E) -7-O-glucopyranoside compound¹³And C spectrum.

FIG. 4 shows the result of glucose absorption promotion detection of apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside, which is a flavonoid C-glycoside compound detected in example 2 of the present invention, on liver cell line FL83B cells cultured ex vivo.

FIG. 5 is a graph showing the response of detecting flavone C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside in example 2 of the present invention to the change in blood glucose in diabetic ICR mice when they are subjected to an oral glucose tolerance test.

FIG. 6 is a bar graph comparing the area under the curve (AUC) of FIG. 1 in example 2 of the present invention with the change in blood glucose in diabetic ICR mice in the flavonoid C-glycoside compound apigenin6-C- [ arabinopyranosyl- (1' → 2 ") -glucopyranoside ] -7-O-glucopyranoside assay.

Detailed Description

The present invention will be described in detail with reference to the following examples: