CN115053963A

CN115053963A - Composition for improving body temperature and promoting body surface microcirculation

Info

Publication number: CN115053963A
Application number: CN202210747147.1A
Authority: CN
Inventors: 邓昌勇; 徐旻珺; 黄晓敏
Original assignee: Sirio Pharma Co Ltd
Current assignee: Sirio Pharma Co Ltd
Priority date: 2022-06-28
Filing date: 2022-06-28
Publication date: 2022-09-16

Abstract

A composition for improving body temperature and promoting microcirculation of body surface is provided. The present invention relates to a composition comprising 5-450 parts by weight of a citrus extract, 75-625 parts by weight of a green coffee bean extract and 1.25-175 parts by weight of a ginger extract. The composition has definite components and effects, safely realizes the decoupling of substance oxidation and ATP generation by stimulating fat to generate heat, releases energy in the form of heat, has no toxic or side effect, and can be applied to products for warming bodies, improving blood circulation or promoting metabolism and reducing fat.

Description

Composition for improving body temperature and promoting body surface microcirculation

Technical Field

The invention belongs to the technical field of food, and particularly relates to a composition for increasing body temperature and promoting body surface microcirculation by fat browning.

Background

With the economic development and improvement of living standard of people, the change of the dietary structure and the reduction of the exercise amount of modern people cause the sub-health problems of low basal metabolic rate, obesity and the like, excessive fat affects the operation of a blood circulation system, the blood viscosity of an obese patient is high, the blood flow rate is slow, and the incidence rate of abnormal microcirculation is higher than that of normal people. When the circulatory system is not smooth, the poor metabolism of the human body is aggravated, the basal metabolic rate is reduced, a vicious circle is formed, the occurrence of obesity and cardiovascular diseases is aggravated, and the human health is harmed.

Body fat is mainly divided into two forms, White Adipose Tissue (WAT) and Brown Adipose Tissue (BAT). Most of the fat in the human body is white fat, which is stored in the subcutaneous space (subcutaneous fat) and around the viscera (visceral fat), and is the main site for storing energy in the body. When the human body takes too much energy without being consumed, white fat is formed and stored as a spare fuel. The proportion of brown fat is high in human infants, and only a small amount of brown fat cells are in adults and are mainly located on neck, clavicle, paravertebral parts, mediastinum and other parts. Brown fats do not store energy and their main function is to burn fat and promote energy expenditure. Brown adipocytes contain a large number of mitochondria, and brown fat induces proton leakage in the respiratory chain to generate heat and consume energy through uncoupling protein 1 on the inner membrane of mitochondria. Thus, activation of brown fat to produce heat may promote energy expenditure and increase body temperature.

Recent studies have found that a "beige adipocyte" can be transformed between white fat and brown adipocyte. Under basal conditions, beige adipocytes have a similar function and morphology to white adipocytes, which differentiate into brown adipocytes and begin to produce heat under cold or some hormonal stimuli, and this induced conversion to a brown adipose phenotype is called white lipobrowning. The amount of brown fat is increased through browning of white fat, and the brown fat is activated to generate heat, so that the oxidation of nutrient substances and the uncoupling of ATP generation are realized, and the conversion of energy to heat is increased.

In the early twentieth century, dinitrophenol was used abroad as an oxidative phosphorylation decoupling agent, and a large amount of energy for synthesizing ATP was used for generating heat. Because of its ability to raise body temperature and increase metabolic rate, it is widely used in weight-loss drugs, but it has obvious toxic and side effects, and 20-50mg/kg dose can cause death, so it is forbidden. Although dinitrophenol cannot be used in the human body, the mechanism of action of dinitrophenol to improve body temperature and metabolic capability remains to be studied and referred. The liquorice and dried ginger decoction is used for warming the body in a traditional Chinese medicine formula for warming interior and nourishing commonly used in China, such as the liquorice and dried ginger decoction used for dispelling cold and treating cold limbs in the 'golden kui-Yao L ü e'. However, the traditional Chinese medicine decoction needs to be decocted, is inconvenient to take, has bitter taste, long treatment course and slow response time and the like. In addition, traditional Chinese medicine formula for promoting blood circulation and removing blood stasis is commonly used for dredging microcirculation, such as compound salvia miltiorrhiza dripping pills for promoting blood circulation and removing blood stasis. In 2021, a patent (CN 114225006 a) uses brown fat cell secretory peptide to activate adipose tissue energy metabolism to achieve body temperature elevation, and can be applied to drugs, health products or food additives by oral administration or injection. Although the brown fat cell secretory peptide plays a role in generating heat by stimulating the browning of white fat, the body temperature is raised, but the peptide has poor physical and chemical stability, the bioavailability of an oral peptide preparation is low, and the biological activity of the peptide is influenced.

Based on the above, the development of an oral preparation which is safe, effective, convenient to use, high in stability, mild and capable of increasing the local body temperature and promoting the body surface microcirculation is of great significance to the human health. Many researches have found that a plurality of compounds capable of promoting white fat cells to generate mitochondria or promoting the expression of uncoupling proteins exist in natural products, so that finding and developing a composition capable of inducing white fat cells to brown and simultaneously stimulating brown fat cells to generate heat is one of effective strategies for increasing body temperature and improving circulation.

Disclosure of Invention

In view of the problems of the prior art, the inventors have found a novel plant extract composition which achieves the conversion of energy in a human body into heat, gently raises the local body temperature of the human body, and promotes the microcirculation of the body surface by inducing the browning of white adipocytes and activating the heat generation of brown adipocytes.

In one aspect, the present invention provides a composition comprising 5-450 parts by weight of a citrus extract, 75-625 parts by weight of a green coffee bean extract, and 1.25-175 parts by weight of a ginger extract.

In one embodiment, the citrus extract comprises from 1 wt% to 30 wt% hesperetin-7-O-glucoside and from 10 wt% to 30 wt% naringenin-7-O-glucoside.

In one embodiment, the citrus extract comprises 5 wt% hesperetin-7-O-glucoside or 15 wt% naringenin-7-O-glucoside.

In one embodiment, the green coffee bean extract comprises 10 wt% to 60 wt% chlorogenic acid.

In one embodiment, the ginger extract comprises 1 wt% to 20 wt% gingerol.

In one embodiment, the composition further comprises one or more of a sweetener, an acid modulator, a filler, a flavoring agent, a coloring agent, an antioxidant, a thickening agent, a stabilizer, an emulsifier, an anticaking agent, a glidant, or a lubricant.

In one embodiment, the composition is a powder, granule, hard capsule, soft capsule, tablet, soft candy, oral solution, or emulsion.

In one embodiment, the citrus extract is a citrus extract enzymatically hydrolyzed by rhamnosidase.

In one aspect, the invention provides a method for the non-therapeutic purpose of elevating body temperature or promoting superficial microcirculation in a subject.

In one aspect, the invention provides a method of non-therapeutic interest for increasing basal metabolism in a subject.

In one aspect, the invention provides methods of inducing white adipocytes to become brown adipocytes and stimulating the brown adipocytes to produce heat.

In various embodiments, the methods of the invention can comprise administering to a subject a composition described herein.

In various embodiments, the subject is a human.

In one aspect, the invention provides the use of a composition of the invention for elevating body temperature or promoting superficial microcirculation, for increasing basal metabolism in a subject, or for inducing white adipocytes to become brown adipocytes and stimulating brown adipocytes to produce heat in a subject.

Compared with the prior art, the invention has the advantages that:

1. compared with the extracts, the composition has synergistic effects in the aspects of increasing body temperature, promoting body surface microcirculation or inducing white fat cells to become brown fat cells and stimulating the brown fat cells to generate heat;

2. the existing technology for utilizing brown fat to exert the heat-generating function and improve the body temperature is brown fat cell secretory peptide and derivatives thereof. According to the invention, the citrus extract containing hesperetin-7-O-glucoside and naringenin-7-O-glucoside, the green coffee bean extract containing chlorogenic acid and the ginger extract containing gingerol are scientifically proportioned, so that white fat is browned, the number of fat cell mitochondria is increased, and energy consumption and body temperature can be statically improved. Compared with peptide preparations, the plant extract of the composition has more stable physical and chemical properties, simpler and more convenient preparation process and use method, lower cost and higher bioavailability of the prepared oral preparation.

3. The existing means for promoting the body surface microcirculation mainly comprises the traditional Chinese medicine formula for promoting blood circulation and removing blood stasis, such as compound salvia miltiorrhiza dripping pills and the like. The invention raises body temperature by using the heat generated by fat browning, properly raises body temperature to expand capillary vessels, is beneficial to blood passing and promotes body surface microcirculation. The improvement of circulation can also improve the basal metabolism of human body, further improve obesity and cardiovascular diseases. Compared with the traditional Chinese medicine formula for promoting blood circulation and removing blood stasis, the composition has the advantages of good taste, convenient taking and quick response.

4. The composition for increasing the body temperature and promoting the microcirculation of the body surface by utilizing the fat browning, which is prepared by the invention, has the advantages of clear components and effects, wide application range, no toxic or side effect, simple preparation operation, low cost, wide applicable dosage form and convenient production and application.

Drawings

FIG. 1 shows a fluorescence micrograph of 3T3-L1 cells.

FIG. 2 shows a statistical plot of the fluorescence intensity of mitochondrial staining within adipocytes after treatment of different groups.

FIG. 3 is a graph showing the results of lipid droplet staining in mature adipocytes after different groups of treatments.

Figure 4 shows a line graph of the real-time change in local body temperature after the subjects took the respective groups of samples.

FIG. 5 shows the mechanism of the present composition to elevate body temperature and promote body surface by inducing browning of white adipocytes.

Detailed Description

These and other aspects, features and advantages of the present invention will be apparent to those skilled in the art from a reading of the following detailed description and the appended claims. Any feature of one aspect of the invention may be used in any other aspect of the invention. The term "comprising" is intended to be open-ended and may be replaced with "consisting of … …" where appropriate. Herein, percentages refer to weight/weight percentages unless otherwise indicated. Except in the examples, or where otherwise explicitly indicated, all numbers in the specification and claims indicating amounts of material mass, physical properties and so forth, are to be understood as modified by the word "about", and may indicate a value of ± 10% or 5%.

The present invention relates to a composition for elevating body temperature or promoting microcirculation of body surface by using fat browning. The composition may comprise a citrus extract, a green coffee bean extract, and a ginger extract.

The "orange extract" refers to an orange extract containing hesperetin-7-O-glucoside and/or naringenin-7-O-glucoside, which is obtained by cleaning orange fruit, separating, performing enzymolysis, sterilizing/inactivating enzyme, and drying. The citrus extract is subjected to enzymolysis treatment by rhamnosidase in the extraction process, so that the citrus extract is rich in hesperetin-7-O-glucoside and naringenin-7-O-glucoside. The compositions of the present invention comprise from 5 to 450 parts by weight of a citrus extract, for example 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430 or 440 parts by weight of a citrus extract. The hesperetin-7-O-glucoside in the citrus extract used in the invention accounts for 1 wt% -30 wt% and/or the naringenin-7-O-glucoside accounts for 10 wt% -30 wt%. For example, hesperetin-7-O-glucoside can be 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt%, 20 wt%, 21 wt%, 22 wt%, 23 wt%, 24 wt%, 25 wt%, 26 wt%, 27 wt%, 28 wt%, or 29 wt%. naringenin-7-O-glucoside may be 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt%, 20 wt%, 21 wt%, 22 wt%, 23 wt%, 24 wt%, 25 wt%, 26 wt%, 27 wt%, 28 wt%, or 29 wt%. The citrus extract of the invention can meet the national or industrial standards for food or health care products.

The green coffee bean extract is prepared by pulverizing green coffee bean, extracting with water, filtering, concentrating, and drying to obtain chlorogenic acid-containing green coffee bean extract. The composition of the present invention may comprise 75 to 625 parts by weight of green coffee bean extract. For example, the green coffee bean extract is present in an amount of 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, or 620 parts by weight. Chlorogenic acid of the green coffee bean extract may be 10 wt% to 60 wt%, e.g., 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt%, 20 wt%, 21 wt%, 22 wt%, 23 wt%, 24 wt%, 25 wt%, 26 wt%, 27 wt%, 28 wt%, 29 wt%, 30 wt%, 31 wt%, 32 wt%, 33 wt%, 34 wt%, 35 wt%, 36 wt%, 37 wt%, 38 wt%, 39 wt%, 40 wt%, 41 wt%, 42 wt%, 43 wt%, 44 wt%, 45 wt%, 46 wt%, 47 wt%, 48 wt%, 49 wt%, 50 wt%, 51 wt%, 52 wt%, 53 wt%, 54 wt%, 55 wt%, 56 wt%, 57 wt%, 58 wt%, or 59 wt%. The green coffee bean extract of the invention can meet the national or industrial standards for food or health care products.

The ginger extract is prepared by cleaning ginger, pulverizing, extracting with water or ethanol, concentrating, mixing, granulating, sieving, coating, and sieving to obtain ginger extract containing gingerol. The composition of the present invention may comprise 1.25 to 175 parts by weight of ginger extract. For example, the ginger extract is present in an amount of 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, or 170 parts by weight. The ginger extract in the composition of the invention may have a gingerol content of 1 wt% to 20 wt% gingerol, for example 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt% or 19 wt%. The ginger extract can meet the national or industrial standards of food or health care products.

The composition of the present invention may further comprise adjuvants or additives in pharmaceuticals or foods. For example, the compositions of the present invention may further comprise one or more of a sweetener, an acid modulator, a filler, a flavoring agent, a coloring agent, an antioxidant, a thickening agent, a stabilizer, an emulsifier, an anticaking agent, a glidant, or a lubricant. Those skilled in the art can select these adjuvants or additives conventionally to prepare a suitable dosage form. For example, the composition of the present invention may be a powder, granule, hard capsule, soft capsule, tablet, soft candy, oral solution or emulsion.

The compositions of the invention may be used in a variety of non-therapeutic methods, for example, to elevate body temperature or promote surface microcirculation in a subject; for increasing basal metabolism in a subject; or for inducing white adipocytes to become brown adipocytes and stimulating brown adipocytes to generate heat. These methods may comprise administering to a subject a composition according to the invention. The compositions of the invention may be used alone or may be administered with other products that increase basal metabolism or browning of white adipose tissue in a subject, for example, with various brown adipocyte secretory peptides known in the art. Herein, the composition of the invention may be applied to a subject in need thereof, e.g. the subject is a human.

Various embodiments of the present invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.

The present application will be explained in further detail below with reference to examples. However, it will be understood by those skilled in the art that these examples are provided for illustrative purposes only and are not intended to limit the present application.

Examples

Embodiments of the present application will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present application and should not be construed as limiting the scope of the present application. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available. All amounts listed are described in weight percent based on total weight, unless otherwise indicated. This application is not to be construed as limited to the particular embodiments set forth herein.

Examples 1 to 10: preparation of the composition

The green coffee bean extract (20 wt% chlorogenic acid), ginger extract (2 wt% gingerol) and citrus extract (5 wt% hesperetin-7-O-glucoside; 15 wt% naringenin-7-O-glucoside) used in the examples were all commercially available. Alternatively, these extracts may be prepared according to conventional techniques. The citrus extract used in the examples can be prepared according to conventional techniques, in which the citrus juice is subjected to an enzymatic treatment with rhamnosidase. In brief, the citrus extract can be obtained by washing citrus fruit, separating, subjecting to enzymolysis, sterilizing/inactivating enzyme, and drying to obtain citrus extract containing hesperetin-7-O-glucoside and naringenin-7-O-glucoside. The green coffee bean extract is prepared by pulverizing green coffee beans, extracting with water, filtering, concentrating, and drying to obtain green coffee bean extract containing chlorogenic acid. The rhizoma Zingiberis recens extract is prepared by cleaning rhizoma Zingiberis recens, pulverizing, extracting with water or ethanol, concentrating, mixing, granulating, sieving, coating, and sieving to obtain rhizoma Zingiberis recens extract containing gingerol. The compositions of examples 1 to 10 were prepared for experiments by uniformly mixing the respective substances according to the compounding ratios shown in table 1. In addition, comparative examples 1-9 were also prepared for comparison with the compositions of examples 1-10.

TABLE 1 composition of the compositions of examples 1-10

Example 11: composition for promoting production of fat cell mitochondria

Mitochondrial staining experiments of 3T3-L1 adipocytes were performed to demonstrate the ability of the compositions of the present invention to promote mitochondrial generation of adipocytes. The specific process is as follows:

1)3T3-L1 cell induced differentiation

Inoculating 3T3-L1 preadipocytes to a culture plate, culturing with high glucose DMEM containing 10% fetal calf serum at 37 deg.C and 5% CO ₂ Culturing under the condition, preparing the cells into cell suspension by trypsinization when the cells grow to 80% -90% (day 0). After the cells are contacted and inhibited for two days, the prepared inducer is added. The formula of the inducer comprises: 0.5 mmol/L3-isobutyl-1-methylxanthine, 1. mu. mol/L dexamethasone and 10. mu.g/mL insulin. The medium containing the inducer was then replaced with a complete medium containing 5. mu.g/mL of insulin and incubated for 48 hours. Finally, the complete culture medium containing insulin is replaced by a fresh complete culture medium for 10 days, and the fresh culture medium is replaced every 48 hours.

2) Dividing 3T3-L1 cells induced to differentiate for 10 days into a blank group (culture medium), an example 1 group, an example 3 group, an example 4 group, an example 7 group, a comparative example 1 group, a comparative example 2 group, a comparative example 3 group, a comparative example 4 group, a comparative example 5 group, a comparative example 6 group, a comparative example 7 group, a comparative example 8 group and a comparative example 9 group;

3) preparing 1mM of mother liquor from Mito-Tracker Green by using anhydrous DMSO, adding the mother liquor into a fresh cell culture medium according to the proportion of 1:10000 to prepare a Mito-Tracker Green staining working solution, and preheating at 37 ℃ for later use;

4) after each sample group processes (500 mu g/mL) cells for 48 hours, removing the cell culture medium, adding a prepared 37 ℃ preheated Mito-Tracker Green staining working solution, and incubating for 30 minutes with the cells at 37 ℃;

5) the Mito-Tracker Green staining working solution is discarded, a fresh culture medium is used for replacing, then, the observation is carried out by using a fluorescence microscope, the photographing record is carried out, and the fluorescence intensity of each processing group is analyzed by using Image J Image processing software. Mito-Tracker Green is a mitochondrial-specific fluorescent probe, so higher fluorescence intensity in the same size field and laser intensity indicates more mitochondria production.

The fluorescence intensity of each treatment group was analyzed by Image J Image processing software by observing and photographing with a fluorescence microscope. Mito-Tracker Green is a mitochondrial-specific fluorescent probe, so higher fluorescence intensity in the same size field and laser intensity indicates more mitochondria production. The results of the experiment are shown in FIGS. 1 and 2. Compared with the blank control group, the numbers of mitochondria in 3T3-L1 cells after treatment of example 1, example 3, example 4 and example 7 are obviously increased (P < 0.0001), while the numbers of mitochondria in comparative example 2, comparative example 4, comparative example 5 and comparative example 7 are increased to a certain extent (P < 0.05), but the promoting effect of example 1, example 3, example 4 and example 7 on the generation numbers of mitochondria in 3T3-L1 cells is obviously better. The composition can increase the number of mitochondria in fat cells after being compounded in a specific proportion.

TABLE 2 fluorescence intensity statistics table for mitochondrial staining results in adipocytes treated with different groups

Group of	Fluorescence intensity value
		Blank control	2693.4±555.7
Example 1	7053.8±541.1
		Example 3	6278.6±637
Example 4	8822.4±1080.7
		Example 7	6481.0±1506.8
Comparative example 1	3258.6±432.176
		Comparative example 2	3516.8±471.092
Comparative example 3	3040.6±439.1
		Comparative example 4	4060.4±1193.1
Comparative example 5	3592.2±668.5
		Comparative example 6	3412.4±1218.8
Comparative example 7	3282.4±225.8
		Comparative example 8	2639.2±628.8
Comparative example 9	3198.0±375.3

According to FIG. 1, the cells treated with the compositions of examples 1, 3, 4 and 7 have stronger fluorescence intensity than the cells treated with the substances of comparative example. FIG. 2 shows a quantitative comparison of fluorescence intensity (using Student's t-test;. p <0.0001 for each example or comparative example compared to the control; p <0.05 for each example or comparative example compared to the control; n.s, p >0.05 for each example or comparative example compared to the control). As can be seen from fig. 2, the increase in fluorescence intensity of the compositions of examples 1, 3, 4, and 7 relative to the blank is greater than the sum of the increases in fluorescence intensity of each individual component relative to the blank, indicating that the combination of the present invention synergistically increases the mitochondrial number of cells.

Example 12: 3T3-L1 assay lipid droplet deposition experiment:

1)3T3-L1 cell induced differentiation

The preadipocytes 3T3-L1 were inoculated on a culture plate, cultured in a DMEM culture medium containing 10% fetal bovine serum at 37 ℃ under 5% CO2, and after the cells reached 80% -90% growth, the cells were trypsinized to prepare a cell suspension (day 0).

2) Adding inducer and culturing for 2 days. After the cells are contacted and inhibited for two days, the prepared inducer is added. The formula of the inducer comprises: 0.5 mmol/L3-isobutyl-1-methylxanthine, 1. mu. mol/L dexamethasone, 10. mu.g/mL insulin.

3) An insulin-containing medium was added thereto and cultured for 2 days, and the above inducer-containing medium was replaced with a complete medium containing 5. mu.g/mL of insulin and cultured for 48 hours.

4) On day 5 of differentiation, the cells were divided into a blank control group (medium), an example 1 group, an example 3 group, an example 4 group, an example 7 group, a comparative example 4 group, a comparative example 5 group, a comparative example 6 group, a comparative example 7 group, and a comparative example 8 group. Culturing in high-glucose DMEM for 48h, then changing 10% fetal calf serum high-glucose DMEM culture solution containing insulin with the final mass concentration of 5 mug/mL, and continuing to culture for 48h, changing the solution 1 time every 2d, and ending the experiment after 10 days.

5) Oil red dyeing

Removing the culture medium from the treated cells, and washing the cells twice with cold PBS; fixing the cells with 4% paraformaldehyde solution for 60 min; dyeing the fixed cells by using an oil red O dye solution kit; the cells were washed 3 times with 60% isopropanol to remove uncolored oil red O stain, washed once with water, and photographed under a microscope. The results of the experiment are shown in FIG. 3. In fig. 3, the fat droplets of the blank control group were large and round, exhibited a typical white adipose cell morphology, the size of the fat droplets in the 3T3-L1 cells treated in the groups of examples 1, 3, 4, and 7 was significantly smaller and denser than that of the control group, exhibited a brown adipose cell-like morphological feature, and the volume of the fat droplets was also significantly smaller than that of the groups of comparative example 4, 5, 6, 7, and 8. It can be seen that the composition of the present invention can reduce the volume of fat cells after being compounded in a specific proportion, and make fat droplets become small and dense, and present brown fat cell-like characteristics.

Example 13: body temperature detection method for healthy people

1) Experimental samples:

composition set (b): the composition in example 1 and filling auxiliary materials such as skimmed milk powder, xanthan gum, guar gum, sucralose and the like;

comparative example group: the components of comparative examples 1, 2, 3, 4, 5, 6, 7 and 8 and filling auxiliary materials such as skimmed milk powder, xanthan gum, guar gum and sucralose;

blank group: skimmed milk powder, xanthan gum, guar gum, sucralose and other filling auxiliary materials.

2) Test object

Guangdong company 6 healthy adults. All subjects were healthy, had no symptoms such as cold, fever, and the like, had no bad habits such as tonifying, smoking, alcoholism, and the like during the test period, and were voluntarily attended.

3) Experimental methods

The experiment was conducted in a crossover design, with each subject ingesting each of the samples of example 1 and comparative example, with each sample being measured in duplicate, with 2 days between each measurement, and with the ingestion sequence being assigned by a computer generated random number method, with each measurement being controlled at room temperature at 25 ℃.

4) Detecting the index

The temperature above the back of the subject (fugui bag) was measured using an infrared thermometer, and the back temperature of the subject was recorded at 0, 5, 10, 20, 30, 40, 50, 60, 70min before the sample was taken as the initial body temperature (0 min) (table 3). The temperature change curve is prepared by taking time as an abscissa and the body temperature at each time point as an ordinate. The results of the experiment are shown in FIG. 4.

TABLE 3 statistical table of the real-time changes in local body temperature of subjects after taking each group of samples

Table 4: comparison of the composition of example 1 with the compositions of comparative examples 1-3

The body temperature change curves of the blank control group and the groups of example 1, comparative example 2, comparative example 3, comparative example 4, comparative example 5, comparative example 6, comparative example 7 and comparative example 8 are shown in fig. 4, and the body temperature of the patient in the peri-varietal sac was gradually raised immediately after the administration of the composition of the present invention, and the body temperature was raised to the maximum after 20 minutes, and then slowly recovered until the initial body temperature was nearly recovered in 70 minutes. Although each comparative example also exhibited a certain body temperature elevating effect, the body temperature elevating effect and the maintenance time of the example 1 group were superior to those of each comparative example group. The maximum increase in body temperature from the initial body temperature after taking the composition of example 1 of the present invention was 0.52 ℃ and the maximum increases of comparative example 1 (citrus extract alone group), comparative example 2 (green coffee bean extract alone group) and comparative example 3 (ginger extract alone) were 0.14 ℃, 0.16 ℃ and 0.2 ℃ respectively, and the maximum increase in body temperature from the initial body temperature at each measurement time point of the composition of the present invention was greater than the sum of the maximum increases of the citrus extract alone group, the green coffee bean extract group and the ginger extract alone, indicating that the combination of the present invention can synergistically increase body temperature. The composition can promote local body temperature of human body, promote body surface microcirculation, and improve blood circulation by inducing brown white fat cells and stimulating brown fat cells to generate heat (see figure 5).

The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims

1. A composition comprising 5-450 parts by weight of a citrus extract, 75-625 parts by weight of a green coffee bean extract, and 1.25-175 parts by weight of a ginger extract.

2. The composition according to claim 1, wherein the citrus extract comprises from 1 wt% to 30 wt% hesperetin-7-O-glucoside and/or from 10 wt% to 30 wt% naringenin-7-O-glucoside.

3. The composition according to claim 2, wherein the citrus extract comprises 5 wt% hesperetin-7-O-glucoside and/or 15 wt% naringenin-7-O-glucoside.

4. A composition according to any one of claims 1 to 3, wherein the green coffee bean extract comprises 10 wt% to 60 wt% chlorogenic acid.

5. The composition of any one of claims 1-4, wherein the ginger extract comprises 1 wt% to 20 wt% gingerol.

6. The composition of any one of claims 1-5, further comprising one or more of a sweetener, an acid modulator, a filler, a flavoring agent, a coloring agent, an antioxidant, a thickening agent, a stabilizer, an emulsifier, an anticaking agent, a glidant, or a lubricant.

7. The composition according to any one of claims 1-6, which is a powder, granule, hard capsule, soft capsule, tablet, gummy, oral solution or emulsion.

8. The composition according to any one of claims 1-7, wherein the citrus extract is a citrus extract enzymatically hydrolyzed by rhamnosidase.

9. A non-therapeutic method for elevating body temperature or promoting superficial microcirculation in a subject; for increasing basal metabolism in a subject; or for inducing white adipocytes to become brown adipocytes and stimulating brown adipocytes to produce heat, comprising administering to a subject a composition according to any one of claims 1-8, preferably wherein the subject is a human.

10. Use of the composition of any one of claims 1-8 for elevating body temperature or promoting superficial microcirculation, for increasing basal metabolism in a subject, or for inducing white adipocytes to become brown adipocytes and stimulating brown adipocytes to produce heat in a subject.