阅读说明：本技术 烷基间苯二酚在制备用于预防或治疗肥胖症相关疾病产品中的应用 (Use of alkylresorcinols in the preparation of a product for preventing or treating obesity-related diseases ) 是由 王静 刘洁 郝一铭 杨子慧 孙宝国 于 2019-10-16 设计创作，主要内容包括：本发明属于减肥产品技术领域,具体涉及烷基间苯二酚在制备用于预防或治疗肥胖症相关疾病产品中的应用。烷基间苯二酚在制备用于预防和/或治疗肥胖相关疾病以及提高能量代谢、机体产热的产品中的应用,其特征在于,所述产品包含活性成分烷基间苯二酚,所述烷基间苯二酚由如下重量百分比的各单体组成：十七烷基间苯二酚1-10％；十九烷基间苯二酚20-25％；二十一烷基间苯二酚50-55％；二十三烷基间苯二酚5-10％；二十五烷基间苯二酚5-12％。本发明明确了烷基间苯二酚通过提高机体能量代谢或提高机体产热以起到预防或治疗肥胖时对应的各组成单体之间的合适配比。(The invention belongs to the technical field of weight-losing products, and particularly relates to application of alkylresorcinol in preparation of products for preventing or treating obesity-related diseases. Use of alkylresorcinol in the manufacture of a product for the prevention and/or treatment of obesity related diseases and for increasing energy metabolism and body heat production, characterized in that the product comprises as active ingredient alkylresorcinol consisting of the following monomers in weight percent: 1-10% of heptadecyl resorcinol; nonadecyl resorcinol 20-25%; 50-55% of heneicosyl resorcinol; 5-10% of eicosatriylresorcinol; 5-12% of pentacosyl resorcinol. The invention defines the proper proportion of the corresponding monomers when the alkylresorcinol plays a role in preventing or treating obesity by improving the energy metabolism or the heat production of an organism.)

1. Use of alkylresorcinol in the manufacture of a product for the prevention and/or treatment of obesity related diseases and for increasing energy metabolism and body heat production, characterized in that the product comprises as active ingredient alkylresorcinol consisting of the following monomers in weight percent:

1-10% of heptadecyl resorcinol; nonadecyl resorcinol 20-25%; 50-55% of heneicosyl resorcinol; 5-10% of eicosatriylresorcinol; 5-12% of pentacosyl resorcinol.

2. Use according to claim 1, wherein the product contains from 0.4 to 1% by weight of alkylresorcinol.

3. The use according to claim 1, wherein said obesity is high fat diet-induced obesity.

4. Use according to claim 1, wherein the alkylresorcinol has the general formula:

in the formula, R₁Is substituted or unsubstituted C₁₅-C₂₇Straight or branched chain alkyl;

when R1 is a branched alkyl, the branches are 2 to 5 carbon atoms in length;

wherein the substituent is hydroxyl.

5. The use according to claim 1, wherein the alkylresorcinol is used in a concentration range of each monomer: heptadecyl resorcinol 18mg/kg/d-45mg/kg/d, nonadecyl resorcinol 146mg/kg/d-366mg/kg/d, heneicosyl resorcinol 310mg/kg/d-774 mg/kg/d; 56mg/kg/d-141mg/kg/d of tricosyl resorcinol; the pentacosyl resorcinol is 68mg/kg/d-171 mg/kg/d.

6. Use according to any one of claims 1 to 5, wherein the product is a pharmaceutical, food or nutraceutical product.

7. The use of claim 6, wherein the product is a medicament, said medicament further comprising a pharmaceutically acceptable carrier or excipient.

8. The preparation method of the alkyl resorcinol is characterized by comprising the following steps:

s1, soaking wheat bran in absolute ethyl alcohol, stirring, and then performing rotary evaporation to remove the solvent to obtain an extract, wherein the mass volume ratio of the wheat bran to the ethyl alcohol solution is 1:1-1:6 Kg/L;

s2, purifying the extract by a silica gel column to obtain a target product; wherein the mobile phase is dichloromethane, and the flow rate is 5-10L/h;

the specification of the silica gel is 100 meshes to 400 meshes.

9. The method for producing alkylresorcinol according to claim 8,

the density of the extract is 0.90-0.93kg/m³；

In step S2, the volume ratio of the extract to the silica gel is 1: 15.

10. A product for preventing and/or treating obesity-related diseases and increasing energy metabolism and body thermogenesis, which is produced by the method of claim 8 or 9.

Technical Field

The invention belongs to the technical field of weight-losing products, and particularly relates to application of alkylresorcinol in preparation of products for preventing or treating obesity-related diseases.

Background

Alkylresorcinols (ARs) are specific phenolic lipids first found in wheat, rye and the like by Wenkert and the like, and have amphipathy. ARs are a generic term for derivatives of 1, 3-resorcinols substituted in the 5-position by alkyl groups with an odd number of carbon atoms, in an amount of 300-1500. mu.g/g of cereal. Alkylresorcinols are absorbed by the body and are therefore often used as important biomarkers in whole grain diets.

The alkyl chains of ARs are different in length, and some ARs have one to three double bonds or substituents such as ketone groups, hydroxyl groups and the like on the alkyl chains (fatty chains). The biological activity of alkylresorcinols in vivo has been reported in large numbers. It has been found that ARs not only are antibacterial, antimutagenic, anticancer, antiparasitic, antioxidant, but also have activity in inhibiting a variety of enzymes associated with glycolipid metabolism. For example, Tu Jie et al in the literature (Inhibition of white bran and matter active compositions on alpha-glucosidase vitro [ J ]. Pharmacognsky Magazine,2013,9(36):309 and 314.) reported that wheat bran ARs are potential alpha-glucosidase inhibitors for the important target enzyme alpha-glucosidase in type 2 diabetes.

Wheat bran ARs have been reported in Oishi et al (Wheat alkylcarbohydrates supplied high-fat, high-glucose di-induced organism and glucose interaction by creating insulin sensitivity and cholesterol interaction in large mice J. Journal of Nutrition,2015,145(2):199 and 206.) to lower fasting blood glucose levels, improve oral glucose and insulin tolerance, increase fecal cholesterol excretion and lower blood cholesterol levels in obese mice induced by a high-fat high-glucose diet.

Although the biological activity of ARs has been found in all of the above reports, the mechanism of action of ARs in organisms, particularly humans, is unknown and even controversial due to the complexity of their components. The results of studies on the resistance of alkylresorcinols to high fat diet-induced weight gain and adipose tissue content by Katsutaka Oishi and Rania Agil, for example, are not identical. KatsutaOishi et al (Wheat alkylresorcinols supplied High-Fat, High-sugar di-induced sensitivity and glucose interaction by creating in the muscle of choice [ J ] Journal of Nutrition,2015,145 (2)) consider alkylresorcinols to have a better effect against obesity, while Rania Agil et al (Tritical nAlkylresorcinols enhanced Resistance to oxygen Stress in Rice field a High-Fat di [ J ] Foods,2016,5 (4)) consider alkylresorcinols to have a poorer effect against obesity. Although both attempt to explain this difference: the content of a certain monomer in the alkylresorcinol is different; however, no explanation is given on how the structural and ratio of the monomers in the ARs can be changed to produce better resistance effect. Particularly, the prior art does not report on the aspect of improving the heat production of the body by improving the breathing rate of the body.

Furthermore, up to now, there has been no report on the use of alkylresorcinols in products for the prevention and/or treatment of obesity.

Disclosure of Invention

The invention aims to provide a product taking alkylresorcinol as an active ingredient, which is applied to products for preventing and/or treating obesity-related diseases and improving energy metabolism and body heat production.

Another object of the present invention is to provide a method for preparing the alkylresorcinol.

It is still another object of the present invention to provide alkylresorcinols prepared by the preparation method.

In order to achieve the above object, one of the technical solutions of the present invention is:

use of alkylresorcinol in the manufacture of a product for the prevention and/or treatment of obesity related diseases and for increasing energy metabolism and body heat production, characterized in that the product comprises as active ingredient alkylresorcinol consisting of the following monomers in weight percent:

1-10% of heptadecyl resorcinol; nonadecyl resorcinol 20-25%; 50-55% of heneicosyl resorcinol; 5-10% of eicosatriylresorcinol; 5-12% of pentacosyl resorcinol.

Preferably, the product has an alkylresorcinol content of 0.4 to 1 wt.%.

Preferably, the obesity is high fat diet-induced obesity.

Preferably, the alkylresorcinol has the formula:

in the formula, R₁Is substituted or unsubstituted C₁₅-C₂₇Straight or branched chain alkyl;

when R1 is a branched alkyl, the branches are 2 to 5 carbon atoms in length;

wherein the substituent is hydroxyl.

Preferably, the concentration ranges of each monomer in the alkylresorcinol are respectively as follows: heptadecyl resorcinol 18mg/kg/d-45mg/kg/d, nonadecyl resorcinol 146mg/kg/d-366mg/kg/d, heneicosyl resorcinol 310mg/kg/d-774 mg/kg/d; 56mg/kg/d-141mg/kg/d of tricosyl resorcinol; the pentacosyl resorcinol is 68mg/kg/d-171 mg/kg/d.

Preferably, the product is a medicament, food or health product.

Preferably, the product is a medicament, which further comprises a pharmaceutically acceptable carrier or adjuvant.

In another embodiment of the present invention, there is provided a method for preparing alkylresorcinol as described above, which comprises the steps of:

s1, soaking wheat bran in absolute ethyl alcohol, stirring, and then performing rotary evaporation to remove the solvent to obtain an extract, wherein the mass volume ratio of the wheat bran to the ethyl alcohol solution is 1:1-1:6 Kg/L;

s2, purifying the extract by a silica gel column to obtain a target product; wherein the mobile phase is dichloromethane, and the flow rate is 5-10L/h;

the specification of the silica gel is 100 meshes to 400 meshes.

Preferably, the density of the extract is 0.90-0.93kg/m³；

In the step S2, the mass ratio of the extract to the silica gel is 1:15 (v/v).

Preferably, the source of the wheat bran may be selected from wheat of jimai 22 in the regions of south river, north river, east Shandong and Anhui.

In still another embodiment of the present invention, there is provided a product for preventing and/or treating obesity-related diseases and increasing energy metabolism and body heat generation, which is prepared by the method as described above.

Preferably, the alkylresorcinol is used in a concentration of 600mg/kg/d to 1500mg/kg/d in mice.

When the product is a medicament, the product can be introduced into the body such as muscle, intradermal, subcutaneous, intravenous, mucosal tissue by physical or chemical mediated methods such as injection, oral administration, injection, and permeation; or mixed or coated with other materials and introduced into body.

When the composition is applied to the aspects of medicines, beverages, foods or health products and the like, one or more pharmaceutically or food acceptable carriers or auxiliary materials can be added when needed. The carrier or adjuvant comprises conventional diluent, filler, adhesive, wetting agent, disintegrating agent, absorption enhancer, surfactant, adsorption carrier, lubricant, excipient, etc. in pharmaceutical and food fields.

Compared with the prior art, the invention has the following beneficial effects:

(1) the invention provides a product for preventing or treating obesity, which takes alkyl resorcinol as an active ingredient, and the product defines the proper proportion of corresponding components when the alkyl resorcinol is used for preventing or treating obesity by improving the energy metabolism or the heat production of an organism.

The product can be used for preventing or treating obesity induced by high fat diet by improving energy metabolism or heat production.

(2) Animal experiments prove that the alkylresorcinol provided by the invention can improve the problems of high fat diet-induced mouse weight gain, glucose tolerance reduction, insulin resistance increase, respiratory capacity metabolism reduction and the like.

Drawings

FIG. 1 is a graph of the effect of ARs on high fat diet induced body weight in C57BL/6 mice;

FIG. 2 is a graph of the effect of ARs on high fat diet induced liver weight in C57BL/6 mice;

FIG. 3 is a graph of the effect of ARs on the weight of subcutaneous fat induced by high fat diet in C57BL/6 mice;

FIG. 4 is a graph showing the effect of ARs on the induction of epididymal fat weight in C57BL/6 mice on high fat diet;

FIG. 5 is a graph of the effect of ARs on the area of the glucose tolerance curve in high fat diet-induced C57BL/6 mice;

FIG. 6 shows the basal blood glucose values of ARs induced by C57BL/6 mice on high-fat diet;

FIG. 7 is a graph of the effect of ARs on high fat diet induced insulin tolerance in C57BL/6 mice;

FIG. 8 is the blood glucose values of ARs induced by C57BL/6 mice on high fat diet;

FIG. 9 is a graph of the effect of ARs on the rate of respiratory oxygen consumption induced by high fat diet in C57BL/6 mice;

FIG. 10 is a graph of the effect of different ARs on the respiratory rate of mature adipocytes.

Detailed Description

The invention is further illustrated by the following examples. These examples are for illustrative purposes only and do not limit the scope and spirit of the present invention.