WO2023282624A1

WO2023282624A1 - Composition for preventing or ameliorating obesity comprising anchovy extract or neochlorogenic acid as active ingredient

Info

Publication number: WO2023282624A1
Application number: PCT/KR2022/009765
Authority: WO
Inventors: 이선희; 신유경; 김현재; 안혜신; 나창선
Original assignee: 코스맥스바이오 주식회사
Priority date: 2021-07-08
Filing date: 2022-07-06
Publication date: 2023-01-12
Also published as: KR20230010116A

Abstract

The present invention relates to a composition for preventing or ameliorating obesity comprising an Adenocaulon himalaicum extract or neochlorogenic acid as an active ingredient. The composition comprising an Adenocaulon himalaicum extract or neochlorogenic acid as an active ingredient, according to one aspect, has an effect of inhibiting fat accumulation and reducing body fat, and can be effectively used for obesity and metabolic diseases.

Description

Composition for preventing or improving obesity containing anchovy extract or neochlorogenic acid as an active ingredient

It relates to a composition for preventing or improving obesity comprising anchovy extract or neochlorogenic acid as an active ingredient.

Obesity is a very serious disease that is rapidly increasing in many countries around the world but has no medically effective treatment. The World Health Organization (WHO) defines a body mass index (BMI) of 30 or more as obesity, and the average obesity rate in OECD member countries is 19.5%, and the rate is gradually increasing.

Obesity refers to the state of excessive accumulation of fat in the body due to genetic or lifestyle causes, and causes diseases such as adult diseases and chronic degenerative diseases. are doing Secondary complications such as hyperlipidemia, hypertension, arteriosclerosis, diabetes, and fatty liver caused by excessive fat accumulation and social disorders that can be caused by obesity are problems.

The world's obese population is rapidly increasing despite the fact that the World Health Organization (WHO) declared obesity as the new epidemic of the 21st century in 2013 and the whole world declared war on obesity. A new problem is emerging in the field of anti-obesity and obesity treatment in that inducing individual behavioral change to prevent obesity is not a perfect alternative for individuals leading busy lives in complex industrial informatization. And, despite the development of basic medical and biological research on obesity, the realistic increase in obesity shows a gap between these two factors. Therefore, there is a need for development and research on food and cosmetics that are more accessible and can achieve a long-term anti-obesity effect.

3T3-L1 Adipocyte (preadipocyte) activates many transcription factors during the differentiation process to accumulate fat. Representative differentiation factors include C/EBPa (CCAAT/enhancer binding protein alpha) and PPARγ (Peroxisome proliferator) induced by it activated receptor gamma). The expression of these high-level factors results in the synthesis of several lower-order proteins. These proteins promote the synthesis and storage of triglycerides, which are harmful to our body, and lead to obesity by accumulating a lot of fat in cells.

Anchovy ( Adenocaulon himalaicum Edgew.) It is a perennial herb of Compositae, and the leaf part is specified as an edible part in the food raw materials notified by the Ministry of Food and Drug Safety. It is about 50 to 100 cm tall, grows in shaded and humid areas, and has been used for trauma treatment, stopping coughing, and folk remedies such as hemostatic agents and anti-inflammatory agents.

Mechanism studies on the inhibition of fat accumulation in a composition for inhibiting fat formation and reducing body fat using an anchovy extract ( Adenocaulon himalaicum Edgew.) or neochlorogenic acid as an active ingredient have not been conducted. Therefore, the present inventors conducted a direct efficacy study on fat accumulation inhibition with the above material.

Accordingly, the inventors of the present invention, as a result of research efforts to overcome the problems of the prior art, found that anchovy ( Adenocaulon himalaicum Edgew.) extract or neochlorogenic acid has an effect of inhibiting fat formation and reducing body fat, and the present invention has been completed

One aspect is anchovy ( Adenocaulon himalaicum Edgew.) Extract; Or to provide a health functional food composition for preventing or improving obesity comprising neochlorogenic acid represented by the following formula (1) or a food chemically acceptable salt thereof as an active ingredient:

[Formula 1]

.

Another aspect is anchovy ( Adenocaulon himalaicum Edgew.) extract; Alternatively, to provide a health functional food composition for preventing or improving metabolic diseases comprising neochlorogenic acid represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

Another aspect is anchovy ( Adenocaulon himalaicum Edgew.) extract; Or to provide a pharmaceutical composition for preventing or treating obesity containing neochlorogenic acid represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

Another aspect is anchovy ( Adenocaulon himalaicum Edgew.) extract; Or to provide a pharmaceutical composition for preventing or treating metabolic diseases comprising neochlorogenic acid represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

Another aspect is anchovy ( Adenocaulon himalaicum Edgew.) extract; Or to provide a cosmetic composition for preventing or improving cellulite containing neochlorogenic acid represented by Formula 1 or a cosmetically acceptable salt thereof as an active ingredient.

Another aspect is an effective amount of an anchovy ( Adenocaulon himalaicum Edgew.) extract; Or to provide a method for preventing, improving or treating obesity or metabolic diseases comprising administering neochlorogenic acid or a pharmaceutically acceptable salt thereof represented by Formula 1 to a subject in need thereof. .

Another aspect is anchovy ( Adenocaulon himalaicum Edgew.) extract; Or, neochlorogenic acid represented by the following formula (1) or a pharmaceutically acceptable salt thereof is used to prepare a composition for preventing, improving or treating obesity or metabolic diseases.

One aspect is anchovy ( Adenocaulon himalaicum Edgew.) Extract; Or, to provide a health functional food composition for preventing or improving obesity comprising neochlorogenic acid represented by Formula 1 or a food chemically acceptable salt thereof as an active ingredient:

[Formula 1]

.

The anchovy extract may be an extract extracted by a solvent from the whole aerial part of the tree, a part thereof, or a material derived therefrom. The part may be a tree stem, root, leaf, flower, petal, seed (seed), fruit flesh, fruit skin, or fruit, and preferably may be a leaf. Whole trees, parts thereof, or materials derived therefrom used for extraction may be ground or minced or suitably dried.

The anchovy extract can be extracted by any extraction method, such as hot water extraction, solvent extraction, distillation extraction, and supercritical extraction, which have been conventionally used to extract natural plants, and preferably water, organic solvents, or mixed solvents thereof Characterized in that it is extracted as. The organic solvent may be at least one selected from the group consisting of alcohols having 1 to 4 carbon atoms, such as ethanol, methanol, isopropanol, and butanol. In addition, the alcohol may contain alcohol. The alcohol concentration of the aqueous alcohol solution is 1 to 99.5 (v / v)%, for example, 10 to 99.5 (v / v)%, 1 to 70 (v / v)%, 1 to 40 (v / v)% , 5 to 50 (v/v)%, 5 to 40 (v/v)%, 10 to 50 (v/v)%, or 10 to 40 (v/v)%.

The extraction is 3 to 50 (w / w) times, for example, 3 to 40 (w / w) times, 3 to 30 (w / w) times, 5 to 50 (w / w) times the extraction solvent with respect to the anchovy value /w) times, 5 to 40 (w/w) times, 5 to 30 (w/w) times, or 4 to 40 (w/w) times. For example, it may include adding 3 to 50 kg of the extraction solvent based on 1 kg of the material derived from the anchovy.

The extraction may be performed by hot water extraction, immersion extraction, supercritical extraction, subcritical extraction, reflux cooling extraction, steam distillation, high pressure enzymatic digestion, ultrasonic extraction, elution, compression, and the like.

The extraction is performed at 4°C to 90°C, such as 4°C to 80°C, 4°C to 70°C, 5°C to 80°C, 10°C to 70°C, 15°C to 70°C or 20°C to 70°C. it may be The extraction time may vary depending on the selected temperature and may be 1 hour to 2 months, for example, 1 hour to 1 month, 1 hour to 10 days, 1 hour to 5 days, 1 hour to 3 days, 1 hour to 2 days. , 1 hour to 1 day, 1 hour to 10 hours, 2 hours to 1 month, 2 hours to 15 days, 2 hours to 10 days, 2 hours to 5 days, 2 hours to 3 days, 2 hours to 2 days, 2 hours to 1 day or 2 hours to 10 hours. The extraction may include mixing the whole anchovy, a part thereof, or a material derived therefrom in the solvent and leaving it for a certain period of time. The standing may include suitable agitation. The extraction may be repeated one or more times, for example 1 to 5 times.

In the extraction, plant residues and extracts may be separated by a known method such as filtration. The extraction may also include removing the solvent from the obtained extract by a known method such as concentration under reduced pressure. The extraction may also include preparing a dried extract by drying the obtained extract, such as lyophilization.

The neochlorogenic acid may be isolated from the anchovy extract, and specifically, may be a fraction of the anchovy extract. The fraction refers to a material containing a specific component separated from the extract. The neochlorogenic acid may be separated and purified using column chromatography. The chromatography is silica gel column chromatography, HP-20 column chromatography, RP-18 column chromatography, LH-20 column chromatography ( LH-20 column chromatography), high-performance liquid chromatography, or a combination thereof can be selected and used.

In one embodiment, the anchovy extract or the neochlorogenic acid is 0.0001% to 90.0% by weight, for example, 0.01% to 60% by weight, 0.01% to 40% by weight, 0.01% by weight based on the total weight of the composition to 30% by weight, 0.01% to 20% by weight, 0.01% to 10% by weight, 0.01% to 5% by weight, 0.05% to 60% by weight, 0.05% to 40% by weight, 0.05% to 30% by weight % by weight, 0.05% to 20% by weight, 0.05% to 10% by weight, 0.05% to 5% by weight, 0.1% to 60% by weight, 0.1% to 40% by weight, 0.1% to 30% by weight , 0.1% to 20%, 0.1% to 10%, 0.1% to 5%, 5 to 20%, 5 to 18%, 6 to 15%, 8 to 15% or 7 to 10% by weight. However, in the case of long-term intake for the purpose of health and hygiene or health control, it may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

The anchovy extract or the neochlorogenic acid may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method.

In one embodiment, the anchovy extract and/or the neochlorogenic acid may inhibit lipogenesis or reduce body fat. The present inventors confirmed the effect of the anchovy extract and/or the neochlorogenic acid to inhibit lipogenesis and reduce body fat, thereby effectively preventing or improving obesity, and metabolic diseases caused by obesity can also be effectively prevented or treated. confirmed.

In addition, the anchovy extract and/or the neochlorogenic acid may promote energy metabolism. It was confirmed that the anchovy extract and / or neochlorogenic acid according to one embodiment promotes phosphorylation of AMPK (AMP-activated protein kinase) and reduces the expression of PPARγ, C / EBPα and SREBP-1, promoting energy metabolism By doing so, it was confirmed that obesity and metabolic diseases can be prevented, improved or treated. In addition, it was confirmed that the anchovy extract and/or neochlorogenic acid according to one embodiment also reduced obesity-related hormones such as leptin and insulin, thereby effectively preventing, improving, or treating obesity.

The term "obesity" refers to a condition in which body fat is excessive, and generally refers to a case in which body weight is higher than normal, but even if the body weight is not overweight, obesity is diagnosed when the proportion of body fat among body components is high. Adults and children It refers to a disease that affects everyone.

Another aspect is anchovy ( Adenocaulon himalaicum Edgew.) extract; Or, to provide a health functional food composition for preventing or improving metabolic diseases comprising neochlorogenic acid represented by Formula 1 or a food chemically acceptable salt thereof as an active ingredient:

[Formula 1]

.

The term "metabolic disease" may refer to a disease caused by excessive synthesis or accumulation of fat due to abnormal energy metabolism in the body due to various causes such as excessive energy intake or hormonal imbalance. Thus, metabolic diseases can be caused by obesity. The type of the metabolic disease is not particularly limited, but may be at least one selected from the group consisting of fatty liver, diabetes, hypertension, hyperlipidemia, hypercholesterolemia, dyslipidemia, and arteriosclerosis.

The term "acceptable" means exhibiting properties that are not toxic to cells or humans exposed to the composition.

The term "acceptable salt" refers to a salt prepared using a specific compound according to one aspect with a relatively non-toxic acid or base. When the compounds contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of base in neat solution or in a suitable inert solvent. Pharmaceutically acceptable base addition salts include salts of sodium, potassium, calcium, ammonium, organic amines, or magnesium or similar salts. When the compounds contain relatively basic functional groups, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of an acid in neat solution or in a suitable inert solvent. Pharmaceutically acceptable acid addition salts include salts of inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, hydrogen carbonate ion, phosphoric acid, hydrogen phosphate ion, dihydrogen phosphate ion, sulfuric acid, hydrogen sulfate ion, hydroiodic acid or phosphorous acid; and salts of organic acids such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, and methanesulfonic acid. and salts of amino acids (eg, arginine) and salts of organic acids such as glucuronic acid.

The acceptable salts can be synthesized by conventional chemical methods from parent compounds containing acidic or basic moieties. Generally, these salts are prepared by reacting the free acid or base form of these compounds with an appropriate stoichiometric amount of the base or acid, either in water or in an organic solvent or in a mixture of the two. In general, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol or acetonitrile are preferred.

The "health functional food" refers to a food manufactured and processed by extracting, concentrating, refining, mixing, etc., a specific ingredient as a raw material or a specific ingredient contained in a food raw material for the purpose of supplementing health. It refers to food designed and processed to sufficiently exert biological control functions such as defense, regulation of circadian rhythm, prevention and recovery of disease, etc. The health functional food composition may perform functions related to prevention and improvement of obesity and prevention and improvement of metabolic diseases.

There is no particular limitation on the type of food. Examples of foods to which the above substances may be added include powders, granules, tablets, capsules, pills, gels, jellies, suspensions, emulsions, syrups, tea bags, leached teas, and formulations selected from the group consisting of health drinks, etc. It includes all health foods in the usual sense.

The health beverage composition of the present invention may include various flavoring agents or natural carbohydrates as additional components, like conventional beverages. The aforementioned natural carbohydrates may include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, natural sweeteners such as dextrin and cyclodextrin, and synthetic sweeteners such as saccharin and aspartame. The proportion of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

The health functional food may include food additives acceptable in food science, and may include appropriate carriers commonly used in the manufacture of health functional food.

In addition to the above, the composition of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages; and the like. In addition, the composition of the present invention may include fruit flesh for preparing natural fruit juice, fruit juice beverages, and vegetable beverages. These components may be used independently or in combination. The ratio of these additives is not critical, but is generally selected in the range of 0.01 to 0.1 part by weight per 100 parts by weight of the composition of the present invention.

Another aspect is anchovy ( Adenocaulon himalaicum Edgew.) extract; Or providing a pharmaceutical composition for preventing or treating obesity comprising neochlorogenic acid or a pharmaceutically acceptable salt thereof represented by Formula 1 below as an active ingredient:

[Formula 1]

.

Another aspect is anchovy ( Adenocaulon himalaicum Edgew.) extract; Or providing a pharmaceutical composition for preventing or treating metabolic diseases comprising neochlorogenic acid represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient:

[Formula 1]

.

Another aspect is an effective amount of an anchovy ( Adenocaulon himalaicum Edgew.) extract; Or, it provides a method for preventing, improving or treating obesity or metabolic disease, comprising administering neochlorogenic acid represented by Formula 1 or a food chemically acceptable salt thereof to a subject in need thereof.

Another aspect is anchovy ( Adenocaulon himalaicum Edgew.) extract; Alternatively, neochlorogenic acid represented by Formula 1 or a pharmaceutically acceptable salt thereof is used for preparing a composition for preventing, improving or treating obesity or metabolic diseases.

The metabolic disease may be one or more selected from the group consisting of fatty liver, diabetes, hypertension, hyperlipidemia, hypercholesterolemia, dyslipidemia, and arteriosclerosis.

The term "pharmaceutical composition" can refer to a molecule or compound that imparts some beneficial effect upon administration to a subject. Beneficial effects may include enabling diagnostic determination; amelioration of a disease, symptom, disorder or condition; reducing or preventing the occurrence of a disease, condition, disorder or condition; and responding to a disease, symptom, disorder or condition in general. In the present invention, the pharmaceutical composition may give a beneficial effect on obesity and metabolic diseases.

The term "prevention" refers to partially or completely delaying or preventing the onset or recurrence of a disease, disorder, or its attendant symptoms, preventing the acquisition or re-acquisition of a disease or disorder, or the risk of acquiring a disease or disorder. tells how to reduce For example, the prevention refers to any action that inhibits or delays the occurrence of obesity and metabolic disease symptoms by administration of the composition according to the present invention.

The term “treatment” includes inhibition, alleviation or elimination of the development of diseases such as obesity and metabolic diseases.

The term "improvement" may refer to any action that at least reduces the severity of parameters associated with alleviation or treatment of conditions, such as obesity and metabolic disease symptoms.

The pharmaceutical composition can be administered parenterally during clinical administration and can be used in the form of a general pharmaceutical preparation. Parenteral administration may refer to administration through an administration route other than oral, such as rectal, intravenous, peritoneal, intramuscular, arterial, transdermal, nasal, inhalation, ocular and subcutaneous administration. When the pharmaceutical composition of the present invention is used as a medicine, it may additionally contain one or more active ingredients exhibiting the same or similar functions.

Types of pharmaceutically active ingredients capable of delivering the active ingredient into the subject include anticancer agents, contrast agents (dye), hormones, anti-hormonal agents, vitamins, calcium agents, mineral preparations, saccharide preparations, organic acid preparations, protein amino acid preparations, detoxifying agents, and enzymes. Preparations, metabolic preparations, diabetes concomitant medicines, tissue regeneration medicines, chlorophyll preparations, pigment preparations, tumor medicines, tumor treatment agents, radiopharmaceuticals, tissue cell diagnostic agents, tissue cell therapy agents, antibiotics preparations, antiviral agents, complex antibiotics preparations, chemicals Therapeutic agents, vaccines, toxins, toxoids, antitoxins, leptospira serum, blood products, biological agents, analgesics, immunogenic molecules, antihistamines, allergy medications, non-specific immunogenic agents, anesthetics, stimulants, psychoactive agents, small molecule compounds, nucleic acids, It may include aptamers, antisense nucleic acids, oligonucleotides, peptides, siRNAs, and micro RNAs.

The pharmaceutical composition may be prepared by further including one or more pharmaceutically acceptable carriers. A pharmaceutically acceptable carrier may be a mixture of saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these components, and, if necessary, antioxidants and buffers. , bacteriostatic agents and other conventional additives may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare formulations for injections such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, or tablets. Furthermore, it can be preferably formulated according to each disease or component by an appropriate method in the art.

When formulating the pharmaceutical composition, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, Witepsol, Macrogol, Tween 61, cacao butter, liurine fat, glycerogeratin and the like may be used.

The pharmaceutical composition may include carbohydrates such as glucose, sucrose or dextran, antioxidants such as ascorbic acid or glutathione, chelating agents, and small molecules in order to increase stability or absorption. Proteins or other Stabilizers can be used as pharmaceuticals.

Another aspect provides a method of treating obesity and metabolic disease comprising administering the pharmaceutical composition to a subject.

The term “administering” means providing a pharmaceutical composition to a subject by any suitable method.

A pharmaceutically effective amount and an effective dosage of the pharmaceutical composition may vary depending on the formulation method, administration method, administration time and/or route of administration of the pharmaceutical composition. In addition, the type and degree of response to be achieved by administration of the pharmaceutical composition, the type of subject to be administered, age, weight, general health condition, symptom or degree of disease, gender, diet, excretion, simultaneous or It may vary according to various factors including drugs and other components of the composition used together in this case, and similar factors well known in the medical field. A person of ordinary skill in the art can readily determine and prescribe an effective dosage for the desired treatment. Administration of the pharmaceutical composition according to the present invention can be administered once a day, divided into several administrations. Therefore, the dosage is not intended to limit the scope of the present invention in any way. The dosage of the pharmaceutical composition may be 1 ug/kg/day to 1,000 mg/kg/day.

The subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat. The subject may be an individual who needs a cure for obesity and metabolic disease or has a desire to lose weight.

Another aspect is anchovy ( Adenocaulon himalaicum Edgew.) extract; Alternatively, a cosmetic composition for preventing or improving cellulite comprising neochlorogenic acid represented by Formula 1 or a cosmetically acceptable salt thereof as an active ingredient is provided:

[Formula 1]

.

The term “cellulite” refers to a condition in which fat protrudes in places, especially in the thigh or buttocks, due to circulatory disorders due to the accumulation of excessive fat and waste products. The cause of cellulite is basically the increase or hypertrophy of fat cells.

The term "prevention or improvement of cellulite" may mean reducing the volume of cellulite, reducing the height of cellulite, removing cellulite, flattening cellulite and its surroundings, and the like. there is.

The composition has an effect of inhibiting body fat accumulation and thus has an effect of preventing or improving cellulite. In addition, due to this effect, the composition has a body slimming effect. The term "body slimming" refers to promoting even redistribution of fat, reducing the volume of a body or a part of the body, eliminating puffiness as a result, in body lines that appear bumpy due to uneven distribution of fat under the skin. It may mean reducing the volume of the body or a part of the body, improving the state of local obesity, dissolving and excreting fat in fat cells, reducing triglyceride and body fluid accumulation in fat cells, and the like.

The cosmetic composition includes lotion (skin lotion), toner, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrient lotion, massage cream, nutrient cream, moisture cream, hand cream, hand sanitizer, foundation, essence, Nutritional essence, packs, soaps, cleansing foams, cleansing lotions, cleansing creams, body lotions, body cleansers, suspensions, gels, powders, pastes, mask packs, and can be prepared into formulations including sheets. Compositions of such formulations may be prepared according to conventional methods in the art. The blending amount of the additional ingredients such as the moisturizing agent can be easily selected by those skilled in the art within a range that does not impair the objects and effects of the present invention.

The cosmetic composition may further include functional additives and ingredients included in general cosmetic compositions in addition to the active ingredients disclosed herein, and commonly used purified water, thickeners, preservatives, stabilizers, solubilizers, surfactants, carriers, A flavoring agent or a combination thereof may be further included. The functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high-molecular peptides, high-molecular polysaccharides, sphingolipids, and seaweed extracts. Alcohols, oils, surfactants, fatty acids, silicone oils, wetting agents, humectants, viscosity modifiers, emulsions, stabilizers, UV scattering agents, UV absorbers, coloring agents, perfumes, and the like may be exemplified as the carrier. Compounds/compositions that can be used as the alcohol, oil, surfactant, fatty acid, silicone oil, wetting agent, humectant, viscosity modifier, emulsion, stabilizer, UV scattering agent, UV absorber, coloring agent, fragrance, etc. are already known in the art. Since there is, those skilled in the art can select and use an appropriate corresponding material / composition. In addition, the cosmetic composition, if necessary, sunscreen, antioxidants (butylhydroxyanisole, gallic acid propyl, ellisorbic acid, tocopheryl acetate, butylated hydroxytoluene, etc.), preservatives (methylparaben, butylparaben , propylparaben, phenoxyethanol, imidazolidinylurea, chlorphenesin, etc.), colorant, pH adjuster (triethanolamine, citric acid, citric acid, sodium citrate, malic acid, sodium malate, fumaric acid, sodium fumarate, succinic acid , sodium succinate, sodium hydroxide, sodium hydrogen phosphate, etc.), humectants (glycerin, sorbitol, propylene glycol, butylene glycol, hexylene glycol, diglycerin, betaine, glycereth-26, methylglue Seth-20, etc.) and lubricants may be further added.

In addition, in the cosmetic composition of each formulation, appropriate components may be selected and blended according to the cosmetic formulation or purpose of use. Since the formulation components and methods may follow conventional techniques, detailed descriptions thereof are omitted herein.

The terms and methods described for the above invention are equally applied between each invention.

According to the composition containing anchovy ( Adenocaulon himalaicum Edgew.) extract or neochlorogenic acid according to one aspect as an active ingredient, it has the effect of inhibiting fat accumulation and reducing body fat, making it useful for obesity and metabolic diseases. can be used

1 is a separation diagram of neochlorogenic acid derived from anchovy extract.

2 shows the ¹ H-NMR spectrum of neochlorogenic acid.

3 shows a ¹³ C-NMR spectrum of neochlorogenic acid.

4 is an HPLC spectrum of anchovy extract and neochlorogenic acid.

Figure 5a is a graph showing the cytotoxicity of the anchovy extract; And Figure 5b is a graph showing the fat accumulation inhibitory effect of anchovy extract.

Figure 6a is a graph showing the cytotoxicity of neochlorogenic acid; And Figure 6b is a graph showing the fat accumulation inhibitory effect of neochlorogenic acid.

Figure 7 is a photograph showing the fat reduction effect of anchovy extract in zebrafish induced obesity.

Figure 8 is a graph showing that there is no change in the body length of the zebrafish when anchovy extract is administered to the zebrafish in which obesity is induced.

Figure 9 is a graph showing the effect of reducing the body weight of zebrafish when anchovy extract is administered to zebrafish in which obesity is induced.

10 is a graph showing the effect of reducing the abdominal circumference of zebrafish when anchovy extract is administered to zebrafish whose obesity is induced.

11 is a graph showing the effect of reducing fat accumulated in the liver of zebrafish when anchovy extract is administered to zebrafish whose obesity is induced.

Figure 12 is a graph showing the change in body weight when the anchovy extract was administered simultaneously with the induction of obesity in mice.

13 is a fat distribution image using dual-energy X-ray absorptiometry in mice when the anchovy extract was administered simultaneously with induction of obesity in order to see the body fat reduction effect of the anchovy extract. And it is a photograph measuring body fat content.

Figure 14a is a graph showing the weight of body fat when the anchovy extract was administered simultaneously with the induction of obesity in mice; And Figure 14b is a graph showing the fat content in the body when the anchovy extract was administered simultaneously with the induction of obesity in mice.

Figure 15a is a graph showing the weight of subcutaneous fat when anchovy extract was administered simultaneously with induction of obesity in mice; 15B is a graph showing liver weight; 15C is a graph showing mesenteric fat weight; 15D is a graph showing brown fat weight; 15E is a graph showing epididymal fat weight; and Figure 15f is a graph showing the renal fat weight.

Figure 16a is a photograph of adipocytes observed under a microscope to see the effect of anchovy extract on reducing the size of fat globules; and FIG. 16B is a graph showing the size of adipocytes.

Figure 17a is the result of confirming the expression of p-AMPK protein in mouse adipose tissue when the anchovy extract was administered; and FIG. 17b shows the results of confirming the expression of PPAR-γ, C/EBPa, and SREBP-1 proteins.

Figure 18a is a graph analyzing leptin content in mouse plasma when anchovy extract was administered; And Figure 18b is a graph analyzing the insulin content.

Figure 19a is a graph analyzing the total cholesterol content in mouse plasma when anchovy extract was administered; And Figure 19b is a graph analyzing the content of low-density cholesterol.

It will be described in more detail through the following examples. However, these examples are intended to illustrate one or more specific examples, and the scope of the present invention is not limited to these examples.

실시예 1: 멸가치(Example 1: Anchovy value ( Adenocaulon himalaicumAdenocaulon himalaicum Edgew.) 추출물의 제조 Edgew.) Preparation of extract

Anchovy extract contained in the composition of the present invention is prepared by the following process. First, after purchasing an anchovy that grows wild in Korea, washing it with distilled water, it was completely dried in a cool place without sunlight until there was no change in weight. After that, after preparing 600 kg of 30% fermented alcohol (30 times, w/w) in the completely dried dried product, 20 kg of the dried product was added. At this time, the mixing ratio of the dry matter and 30% fermented alcohol was 30 times the weight ratio. Next, 30% fermented alcohol mixed with the dried product was put in a constant temperature water bath and stirred and extracted at 60 ° C. for 5 hours. The extracted sample was filtered through a housing filter (10 um) and then concentrated under reduced pressure to obtain a yellow-brown water-soluble powder.

실시예 2: 네오클로로겐산(Neochlorogenic acid)의 제조Example 2: Preparation of Neochlorogenic acid

200 g of the extracted powder obtained in Example 1 was subjected to gel filteration using DIAION HP-20 resin. The developing solvent was subjected to solvent fractionation using a [acetone : distilled water = 0 : 10 ~ 10 : 0 ] mixed solution and divided into 12 small fractions (Fr.1-1-12). Of these, small fraction 4 was purified by RP-MPLC using a [acetonitrile: distilled water = 5:95-100:0] mixed solution to obtain a pure compound 1 single substance.

Next, in order to confirm the structure of Compound 1, liquid chromatography mass spectrometry spectrum, ¹ H-NMR spectrum, and ¹³ C-NMR spectrum were measured.

As a result of measuring the molecular weight using a liquid chromatography mass spectrometer, C ₁₆ H ₁₈ O ₉ was found to be 354.3, and as shown in FIG. 2, in the case of the ¹ H-NMR spectrum, three corresponding to the caffeoyl moiety [δH 7.05 (d, 1H, J = 2.0Hz, H-2' ), 6.94 (dd, 1H, J = 2.0, 8.2 Hz, H-6'), 6.77 (d, 1H,J = 8.2 Hz, H-5')], and the two hydrogens shown as trans double bonds are respectively [δH 7.59 (d, 1H,J = 15.8 Hz, H-3), 6.31 ( d,1H, J = 15.8Hz, H-2)]. [δH 5.35 (m, 1H, Q-3), 4.15 (m, 1H, Q-5), 3.64 (m, 1H, Q-4), 2.21 (m, 1H, Q-2a), 2.14 (m, 2H, Q-6), 1.96 (m, 1H, Q-2b)], six hydrogens corresponding to quinic acid appeared. In the ¹³ C-NMR spectrum, a total of 16 carbons were identified, including 2 methylene carbons, 8 methine carbons, and 6 quaternary carbons, among which 2 carbonyl groups [δ 178.47 , δ 169.19] appeared.

In view of the above points, it was confirmed that the compound 1 was neochlorogenic acid by referring to known literature. The degree of separation of the compound is shown in FIG. 1 . KURITA, SERIKA; KASHIWAGI, TAKEHIRO; EBISU, TOMOYO; SHIMAMURA, TOMOKO; UKEDA, HIROYUKI. Identification of neochlorogenic acid as the predominant antioxidant in Polygonum cuspidatum leaves. Italian Journal of Food Science.2016, 28, 25-31.

실험예 1: 멸가치 추출물 내 네오클로로겐산 함량분석Experimental Example 1: Neochlorogenic acid content analysis in anchovy extract

The extracted powder and neochlorogenic acid obtained in Example 1 of the present invention were analyzed by high performance liquid chromatography (HPLC) and ultraviolet absorbance detector (UV/Vis detector). Waters e2695 Series system, Waters 24489 UV/Vis detector (Worcester, MA, USA), and X select C18 (5 μm, 250 Х 4.6 mm, waters, Milford, Massachusetts, USA) column were used for the HPLC instrument. All solvents were prepared by J.T. HPLC grade solvents purchased from Baker (Phillipsburg, NJ, USA) were used. At the time of analysis, the temperature of the column was set to 35°C, the injection volume was 20 µl, and the measurement wavelength was set to 325 nm. As the mobile phase, acetonitrile (ACN), tertiary distilled water (D.W) and formic acid were used, and 0.1% formicacid ACN -0.1% formicacid D.W (1:9 - 10:0, v /v) The mixed solution was analyzed for 60 minutes. For the analysis sample, 1 g of the extracted powder obtained in Example 1 was precisely weighed, 100 ml of 30% methanol was added, dissolved in an ultrasonic shaker for 30 minutes, cooled at room temperature, and the supernatant was taken and filtered through a 0.22 μm membrane filter. Neochlorogenic acid 10 mg of silver was precisely weighed, added with 20 ml of 50% methanol, dissolved in an ultrasonic shaker for 30 minutes, allowed to cool at room temperature, and then filtered with a 0.22 μm membrane filter after adding methanol. Chromatograms were extracted at 325 nm for each analysis sample, and the anchovy extract peak and neochlorogenic acid peak were compared and analyzed and shown in FIG. 4.

실험예 2: 세포 독성 확인Experimental Example 2: Confirmation of cytotoxicity

The cytotoxicity of the anchovy extract of Example 1 and neochlorogenic acid of Example 2 on epidermal cells was measured. In order to confirm cytotoxicity according to material treatment, 3T3-L1 was attached to a 96-well plate at a concentration of 1.0 X 10 4 cells/well for 24 hours and stabilized. Thereafter, each concentration sample was replaced with the treated medium and cultured for 24 hours. Then, the degree of cell viability was measured by MTT assay.

As a result, as shown in Figure 5, it was confirmed that the anchovy extract and neochlorogenic acid were not cytotoxic.

실험예 3: Oil Red O 염색을 통한 지방축적 억제 평가 Experimental Example 3: Assessment of inhibition of fat accumulation through Oil Red O staining

In this experiment, in order to induce adipocyte differentiation, 3T3-L1 cells were seeded on a plate and cultured in 10% BS medium until the cell density reached 100%. At the stage of cell differentiation, 10% FBS differentiation medium (Insulin 5μg/ml, Dexametasone 1μM, 3-Isobutyl-1-methylxanthine 0.5mM) was treated with anchovy extract at concentrations of 1 ppm, 10 ppm, 25 ppm, and 50 ppm, respectively. , Neochlorogenic acid was treated with 6.25 um, 25 um, 50 um and 100 um, respectively. After 8 days, how much fat accumulation can be inhibited was measured through Oil Red-O staining and quantitative analysis. For visual evaluation, images were taken after staining. Then, the stained cells were completely dried, dissolved in DMSO (Dimethyl Sulfoxide), transferred to a 96-well plate, and absorbance was measured at 450 nm.

As a result, as shown in Figure 6, it was confirmed that the anchovy extract and neochlorogenic acid inhibited fat accumulation. These results indicate that anchovy and neochlorogenic acid can effectively prevent or improve obesity, and also effectively prevent or treat metabolic diseases caused by obesity.

실험예 4: 멸가치 (Experimental Example 4: Anchovy value ( Adenocaulon himalaicum Adenocaulon himalaicum Edgew.) 추출물의 생체 내 (Edgew.) extracts in vivo ( in vivoin vivo ) 효과 분석) effect analysis

4-1. 제브라 피쉬 및 실험 디자인4-1. Zebrafish and experimental design

In order to analyze the in vivo anti-obesity efficacy of the anchovy extract obtained in Example 1, zebrafish fry were prepared by inviotec. First, females and males were placed in a 1:1 ratio in a tank equipped with a net to separate eggs and adult fish, and zebrafish embryos were collected after 12 hours. After collection, it was washed three times using 0.03% sea salt solution to remove foreign substances and reared in an incubator with a 28.5 ° C photoperiod (14 light / 10 dark). Zebrafish fry (3 dpf) after 3 days of fertilization were placed in a petri dish, and then treated for 2 days of rotifer, 6 days of artemia, and 4 days of feed, for a total of 12 days, to prepare an overfeed-induced obese zebrafish model. The overfeed-induced obese zebrafish model was treated with rotifer, artemia, and feed 4 times a day, and the normal control group was treated with rotifer, artemia, and feed twice a day. From the 11th day, the overfeed-induced obese zebrafish model was treated with 100 μg/ml of anchovy extract and 50 μg/ml of Cissus extract as a positive control, and exposed for 24 hours.

4-2. 멸가치 추출물에 의한 체중 및 지방의 감소 효과 분석4-2. Analysis of weight and fat reduction effect by anchovy extract

In order to confirm whether the weight and fat of zebrafish decreased when the anchovy extract obtained in Example 1 was administered, an experiment was performed as follows. After the experiment was completed, the zebrafish fry were anesthetized with 0.02% tricaine, and the body length and belly length of the zebrafish were observed using an optical microscope (Olympus 1Х70, Olympus, Japan). Afterwards, body length and belly length were measured using Focus Lite software, and the weight was checked with a precise electronic scale for analysis and graphed. Statistical analysis was performed using Sigma Plot software (Systat software Inc., USA) and paired t-teat and repeated ANOVA to confirm whether there was a difference between groups in each experimental condition.

As a result, as shown in FIG. 7, the zebrafish (CON) whose obesity was induced compared to the normal control group (NOR) showed a large amount of fat in the abdomen, but the positive control group (PC) and anchovy extract (AH) were administered A decrease in fat was confirmed in one group.

In addition, as shown in Figures 8 to 10 and Tables 1 to 3, compared to the zebrafish (CON) in which obesity was induced, the positive control (PC) and anchovy extract (AH) administered body While there was little change in length, it was confirmed that body weight and abdominal circumference were reduced.

These results indicate that the anchovy extract can effectively prevent or improve obesity by inhibiting fat accumulation, and also effectively prevent or treat metabolic diseases caused by obesity.

	NORNOR	CONCON	AHAH	PCPC
BodyLength(mm)BodyLength(mm)	7.39± 0.227.39 ± 0.22	7.53± 0.307.53 ± 0.30	7.60± 0.227.60 ± 0.22	7.55± 0.297.55 ± 0.29

	NORNOR	CONCON	AHAH	PCPC
BodyWeight(mg)BodyWeight(mg)	0.0467± 0.00760.0467 ± 0.0076	0.1067± 0.00760.1067 ± 0.0076	0.0867± 0.00760.0867 ± 0.0076	0.0600± 0.00500.0600 ± 0.0050

	NORNOR	CONCON	AHAH	PCPC
BellyLength(μm)BellyLength (µm)	1587± 671587 ± 67	1887± 1621887 ± 162	1810± 1291810 ± 129	1668± 01201668 ± 0120

4-3. 멸가치 추출물에 의한 지방간 억제 확인4-3. Confirmation of fatty liver inhibition by anchogachi extract

When the anchovy extract of Example 1 was administered, the following experiment was performed to confirm the reduction of fatty liver in the liver of zebrafish in which obesity was induced. First, the sacrificial zebrafish fry at the end of the experiment were fixed in 4° C. paraformaldehyde (PFA) overnight, and then washed twice with 1X PBS. Thereafter, 80% and 100% propylene glycol were sequentially treated for 20 minutes at room temperature, and zebrafish fry were dyed by exposing overnight to 0.5% Oil Red O in 100% propylene glycol at room temperature to block light. The dyed fry was washed with 1 X PBS, treated with 100% and 80% propylene glycol at room temperature for 30 minutes, respectively, to wash the dye, stored in 80% propylene glycol at 4℃, and examined under an optical microscope (Olympus 1Х70, Olympus , Japan) was used to observe liver fat, and fat size was measured using Focus Lite software.

As a result, as shown in FIG. 11 and Table 4, compared to the zebrafish (CON) in which obesity was induced, the fat accumulated in the liver was reduced in the group administered with the positive control (PC) and anchovy extract (AH). confirmed that it was These results indicate that the anchovy extract can effectively prevent or improve obesity by inhibiting fat accumulation, and also effectively prevent or treat metabolic diseases caused by obesity.

	NORNOR	CONCON	AHAH	PCPC
Lipidaccumulation(mm2)Lipidaccumulation(mm2)	0.024± 0.00280.024 ± 0.0028	0.072± 0.00620.072 ± 0.0062	0.062± 0.00710.062 ± 0.0071	0.048± 0.00690.048 ± 0.0069

실험예 5: 멸가치 추출물(EEAH)의 생체 내 (in vivo) 효과 분석Experimental Example 5: In vivo effect analysis of anchovy extract (EEAH)

5-1. 마우스 및 실험 디자인5-1. Mice and Experimental Design

In order to analyze the in vivo anti-obesity efficacy of anchovy extract, an obese animal model was first prepared. 8-week-old male C57BL/6N mice (specific-pathogen-free (SPF) grade, 20 ± 2 g, Orient Bio) were set into 5 groups as follows, and 8 mice per group were tested: As a normal control, high-fat diet Orlistat, an anti-obesity treatment, was placed in a normal mouse (con), which was not administered with anything, and an obese mouse (HFD), which was induced with a 30% high-fat diet and not administered anything, respectively. was orally administered. As an experimental group, 100 mg/kg and 300 mg/kg of anchovy extract were orally administered to obese mice, respectively. The anchovy extract was orally administered 5 days per week during the administration period. The dark: light cycle was maintained at 12-hour: 12-hour intervals, and water was freely consumed.

5-2. 멸가치 추출물에 의한 체중 및 지방의 감소 효과 분석5-2. Analysis of weight and fat reduction effect by anchovy extract

An experiment was performed to analyze whether the body weight and fat of mice were reduced when the anchovy extract was administered. As a result, when looking at the weight change of mice according to each experimental group and time, the positive control group and the group administered with the anchovy extract could see the weight loss effect (FIG. 12). In particular, it was confirmed that the anchovy 300 mg/kg administered group inhibited weight gain to a similar extent to that of the positive control group.

In addition, in the last week of the animal experiment, fat distribution images and body fat content were measured using dual-energy X-ray absorptiometry for mice in each experimental group, and the animals were sacrificed to separate adipose tissue including epididymal fat. fat weight was measured. The experimental results showed significant differences between groups using Dunnett's post hoc test in the GraphPad Prism statistical program (p ^# <0.05 vs normal control group, p ^* <0.05, p ^** <0.01, P ^*** <0.001 vs obese group) . As a result, it was confirmed that the body fat mass and body fat percentage were reduced in the positive control group and the group administered with the anchovy extract (Figs. 13 and 14). The weights of various adipose tissue and liver tissue analyzed after animal sacrifice were all increased when the high-fat diet was administered, but it was confirmed that the weight of the anchovy extract was significantly decreased in the group administered with the anchovy extract (FIG. 15). In particular, the group administered with 300 mg/kg of anchovy extract showed a degree of reduction similar to that of the positive control group, indicating that the anchovy extract can effectively prevent or improve obesity by suppressing fat accumulation.

5-3. 멸가치 추출물에 의한 지방세포 크기 감소 효과 분석5-3. Analysis of fat cell size reduction effect by anchovy extract

For histological analysis, mouse epididymal adipose tissue was fixed in 4% paraformalin. After dehydration through continuous alcohol concentration gradient (Graded alcohol series) and washing several times, the tissues were embedded in paraffin. Tissue sections were cut to a thickness of 4 μm, and stained with hematoxylin and eosin. In order to confirm the size of white adipocytes, the area of each adipocyte was measured in each section using CellSence software (Olympus Co., USA). As a result, it was confirmed that the size of adipocytes in the group administered with the anchovy extract along with induction of obesity was reduced to a degree similar to that of the normal control group (FIG. 16).

5-4. 멸가치 추출물에 의한 에너지 대사와 관련한 단백질 발현 분석5-4. Analysis of protein expression related to energy metabolism by anchovy extract

AMPK (AMP-activated protein kinase) is activated to maintain energy homeostasis, inhibits fat and cholesterol synthesis, and promotes fatty acid oxidation. In addition, during adipocyte differentiation, initial differentiation is initiated by C/EBPs, which are proteins involved in adipogenesis including C/EBPα, peroxisome proliferator-activated receptor (PPAR)γ, and sterol controlled element-binding protein (SREBP)-1. It promotes terminal differentiation by increasing the expression of transcription factors that regulate genes. Therefore, in order to confirm that the administration of the anchovy extract regulates the expression of AMPK, C/EBPα, PPARγ, and SREBP-1, the protein expression level of the group administered with the anchovy extract along with induction of obesity was analyzed.

Specifically, after mixing the adipose tissue with the protein extraction solution and crushing it using a tissue grinder, the supernatant was obtained by centrifugation at 4 ° C. and 15,000 rpm for 30 minutes, and then a standard curve was prepared using the Bradford method to quantify the protein. After adding 6-fold sample buffer to 30 μg of protein, incubating in a water bath for 5 minutes, electrophoresis was performed using a 10% SDS-PAGE gel, followed by immunoblotting on a PVDF membrane for 1 hour and 20 minutes. After blocking for 1 hour with TBST buffer solution (Tris-buffered saline-Tween 20) containing 5% (w/v) skim milk, anti-p-AMPK, PPARγ, C/EBPα, and SREBP-1 antibodies were added at 1:1000. and reacted at 4°C for 18 hours. After washing three times for 10 minutes with TBST buffer, the cells were reacted with peroxidase-conjugated secondary antibodies at room temperature for 2 hours. After washing three times for 10 minutes with TBST buffer solution, color development and development with a hyper film using an enhanced chemiluminescence kit (Amersham Life Sciences, Amersham, U.K.) The protein changes in each control and experimental group were confirmed by western blot. As a result, When the anchovy extract was administered, it was confirmed that the amount of phosphorylated AMPK protein was increased (FIG. 17a). In addition, it was confirmed that the expression levels of PPARγ, C/EBPα, and SREBP-1, which increased with the induction of obesity, decreased (FIG. 17b).

These results show that anchovy extract effectively prevents or improves obesity through the induction of AMPK phosphorylation, which is important for the anti-obesity effect, and the mechanism of reducing PPARγ, C/EBPα, and SREBP-1, and also effectively prevents metabolic diseases caused by obesity. that it can be prevented or cured.

5-5. 멸가치 추출물에 의한 혈중 렙틴 및 인슐린 변화 분석5-5. Analysis of blood leptin and insulin changes by anchogachi extract

Leptin, a hormone produced primarily by fat cells, plays a role in suppressing food intake, thereby regulating energy balance under normal conditions. However, if you are obese, your sensitivity to leptin is reduced, so you do not feel full even if your leptin level is high. Insulin is secreted by the pancreas and is an important hormone for the synthesis and storage of energy substances. In the case of obesity, due to insulin resistance, the cells do not recognize insulin well and become less sensitive and secrete more insulin.

In order to analyze the effect of the anchovy extract on blood leptin and insulin, the plasma of the group administered with the anchovy extract along with obesity induction was analyzed using an ELISA kit. As a result, as shown in Figure 18, it was confirmed that the contents of leptin and insulin were reduced in the group administered with the anchovy extract with obesity induction. These results suggest that leptin and insulin resistance, which were increased through a high-fat diet, were mitigated by the anchovy extract, which means that obesity can be prevented and treated through these effects.

5-6. 멸가치 추출물에 의한 혈중 콜레스테롤 변화 분석5-6. Blood Cholesterol Change Analysis by Anchogachi Extract

In order to analyze the effect of the anchovy extract on blood total cholesterol and low-density cholesterol, the blood biochemistry test of the group administered with the anchovy extract along with obesity induction was performed using a biochemistry analyzer (AU480 Chemistry Analyzer, Beckman coulter, CA, USA). performed. As a result, as shown in FIG. 19, it was confirmed that the contents of total cholesterol (TC) and low-density cholesterol (LDL) were reduced in the group administered with the anchovy extract along with induction of obesity. These results indicate that the anchovy extract has an effect of preventing obesity by reducing blood cholesterol.

제형예 1: 정제의 제조Formulation Example 1: Preparation of tablets

For the anchovy extract of Example 1 and neochlorogenic acid of Example 2, the ingredients in Table 5 below were mixed and tableted according to a conventional tablet manufacturing method to prepare tablets.

원료명raw material name	단위 중량 (mg)unit weight (mg)	원료명raw material name	단위 중량 (mg)unit weight (mg)
실시예 1Example 1	300.0006300.0006	실시예 2Example 2	10.000010.0000
이산화규소silicon dioxide	15.300015.3000	이산화규소silicon dioxide	15.300015.3000
스테아린산마그네슘Magnesium Stearate	10.800010.8000	스테아린산마그네슘Magnesium Stearate	10.800010.8000
결정셀룰로오스crystalline cellulose	509.4945509.4945	결정셀룰로오스crystalline cellulose	799.4951799.4951
히드록시프로필메틸셀룰로오스Hydroxypropyl Methyl Cellulose	29.070029.0700	히드록시프로필메틸셀룰로오스Hydroxypropyl Methyl Cellulose	29.070029.0700
카르복시메틸셀룰로오스칼슘Carboxymethyl Cellulose Calcium	27.000027.0000	카르복시메틸셀룰로오스칼슘Carboxymethyl Cellulose Calcium	27.000027.0000
글리세린지방산에스테르Glycerin fatty acid ester	0.69300.6930	글리세린지방산에스테르Glycerin fatty acid ester	0.69300.6930
이산화티타늄titanium dioxide	1.46971.4697	이산화티타늄titanium dioxide	1.46971.4697
홍국적색소red national pigment	4.4082 4.4082	홍국적색소red national pigment	4.40824.4082
분말카라멜색소powdered caramel color	1.7640 1.7640	분말카라멜색소powdered caramel color	1.76401.7640

제형예 2: 캡슐제의 제조Formulation Example 2: Preparation of capsules

For the anchovy extract of Example 1 and neochlorogenic acid of Example 2, the ingredients in Table 6 below were mixed according to a conventional capsule preparation method and filled into gelatin capsules to prepare soft capsules.

원료명raw material name	단위 중량 (mg)unit weight (mg)	원료명raw material name	단위 중량 (mg)unit weight (mg)
실시예 1Example 1	5050	실시예 2Example 2	10 10
비타민 Evitamin E	2.252.25	비타민 Evitamin E	2.25 2.25
비타민 Cvitamin C	2.252.25	비타민 Cvitamin C	2.25 2.25
팜유palm oil	0.50.5	팜유palm oil	0.50.5
식물성 경화유hydrogenated vegetable oil	22	식물성 경화유hydrogenated vegetable oil	22
황납Yellow lead	1One	황납Yellow lead	1One
레시틴lecithin	2.252.25	레시틴lecithin	2.252.25
연질캡슐 충진액Soft capsule filling solution	387.75387.75	연질캡슐 충진액Soft capsule filling solution	427.75427.75

제형예 3: 액제의 제조Formulation Example 3: Preparation of liquid formulation

With respect to the anchovy extract of Example 1 and neochlorogenic acid of Example 2, the ingredients in Table 7 below were mixed according to a beverage manufacturing method suitable for taste and filled into a bottle or pouch to prepare a liquid formulation.

원료명raw material name	단위중량 (g)unit weight (g)	원료명raw material name	단위중량 (g)unit weight (g)
실시예 1Example 1	2.50502.5050	실시예 2Example 2	0.50500.5050
산탄검xanthan gum	0.00750.0075	산탄검xanthan gum	0.00750.0075
프락토올리고당액fructooligosaccharide solution	0.75000.7500	프락토올리고당액fructooligosaccharide solution	0.75000.7500
코코넛꽃진액분말Coconut Flower Extract Powder	1.05001.0500	코코넛꽃진액분말Coconut Flower Extract Powder	1.05001.0500
쌍화농축액Ssanghwa Concentrate	1.50001.5000	쌍화농축액Ssanghwa Concentrate	1.50001.5000
홍삼향Red Ginseng Fragrance	0.04500.0450	홍삼향Red Ginseng Fragrance	0.04500.0450
정제수Purified water	9.14259.1425	정제수Purified water	11.142511.1425
원료명raw material name	단위중량 (g)unit weight (g)	원료명raw material name	단위중량 (g)unit weight (g)
실시예 1Example 1	2.50502.5050	실시예 2Example 2	0.50500.5050
산탄검xanthan gum	0.00750.0075	산탄검xanthan gum	0.00750.0075
프락토올리고당액fructooligosaccharide solution	0.75000.7500	프락토올리고당액fructooligosaccharide solution	0.75000.7500
코코넛꽃진액분말Coconut Flower Extract Powder	1.05001.0500	코코넛꽃진액분말Coconut Flower Extract Powder	1.05001.0500
쌍화농축액Ssanghwa Concentrate	1.50001.5000	쌍화농축액Ssanghwa Concentrate	1.50001.5000
홍삼향Red Ginseng Fragrance	0.04500.0450	홍삼향Red Ginseng Fragrance	0.04500.0450
정제수Purified water	9.14259.1425	정제수Purified water	11.142511.1425

제형예 4: 젤리의 제조Formulation Example 4: Preparation of Jelly

For the anchovy extract of Example 1 and neochlorogenic acid of Example 2, the ingredients in Table 8 were mixed according to the jelly manufacturing method suitable for the taste and filled in three cotton cloths to prepare jelly.

원료명raw material name	단위중량 (g)unit weight (g)	원료명raw material name	단위중량 (g)unit weight (g)
실시예 1Example 1	2.00002.0000	실시예 2Example 2	0.50000.5000
푸드겔food gel	0.36000.3600	푸드겔food gel	0.36000.3600
카라기난carrageenan	0.06000.0600	카라기난carrageenan	0.06000.0600
젖산칼슘calcium lactate	0.10000.1000	젖산칼슘calcium lactate	0.10000.1000
구연산나트륨sodium citrate	0.06000.0600	구연산나트륨sodium citrate	0.06000.0600
복합황금추출물complex gold extract	0.02000.0200	복합황금추출물complex gold extract	0.02000.0200
효소처리스테비아Enzymatically Treated Stevia	0.04400.0440	효소처리스테비아Enzymatically Treated Stevia	0.04400.0440
프락토올리고당액fructooligosaccharide solution	5.00005.0000	프락토올리고당액fructooligosaccharide solution	5.00005.0000
적포도농축액Red Grape Concentrate	2.40002.4000	적포도농축액Red Grape Concentrate	2.40002.4000
정제수Purified water	13.956013.9560	정제수Purified water	15.456015.4560

제형예 5: 영양크림의 제조Formulation Example 5: Preparation of nutrient cream

For the anchovy extract of Example 1 and neochlorogenic acid of Example 2, a nourishing cream was prepared according to the conventional method with the composition shown in Table 9 below.

원료명raw material name	함 량 (%)content (%)	원료명raw material name	함 량 (%)content (%)
실시예 1Example 1	1.01.0	실시예 2Example 2	0.20.2
시토 스테롤sitosterol	4.04.0	시토 스테롤sitosterol	4.04.0
폴리글리세릴 2-올레이트 3.0Polyglyceryl 2-oleate 3.0	3.03.0	폴리글리세릴 2-올레이트 3.0Polyglyceryl 2-oleate 3.0	3.03.0
세테아레스-4Ceteares-4	2.02.0	세테아레스-4Ceteares-4	2.02.0
콜레스테롤cholesterol	3.03.0	콜레스테롤cholesterol	3.03.0
디세틸포스페이트dicetyl phosphate	0.40.4	디세틸포스페이트dicetyl phosphate	0.40.4
농글리세린concentrated glycerin	5.05.0	농글리세린concentrated glycerin	5.05.0
선플라우어오일sunflower oil	22.022.0	선플라우어오일sunflower oil	22.822.8
카르복시비닐폴리머carboxyvinyl polymer	0.50.5	카르복시비닐폴리머carboxyvinyl polymer	0.50.5
트리에탄올아민triethanolamine	0.50.5	트리에탄올아민triethanolamine	0.50.5
방부제antiseptic	미량a very small amount	방부제antiseptic	미량a very small amount
향료Spices	미량a very small amount	향료Spices	미량a very small amount
정제수Purified water	잔량balance	정제수Purified water	잔량balance

Although the above composition ratio is generally prepared as a formulation example by mixing suitable ingredients, the mixing ratio and raw materials may be arbitrarily changed as necessary.

Since the extract of the present invention and components derived therefrom are stable in all formulation test conditions, there was no problem with the stability of the formulation.

Claims

Anchovy ( Adenocaulon himalaicum Edgew.) extract; Or a health functional food composition for preventing or improving obesity comprising neochlorogenic acid represented by Formula 1 or a food chemically acceptable salt thereof as an active ingredient:

[Formula 1]

.
The method according to claim 1, wherein the anchovy ( Adenocaulon himalaicum Edgew.) extract is extracted with water, C1 to C4 alcohol, or a mixed solvent thereof, the health functional food composition for preventing or improving obesity.
The method according to claim 1, wherein the neochlorogenic acid is a functional food composition for preventing or improving obesity that is separated from anchovy extract.
The health functional food composition for preventing or improving obesity according to claim 1, wherein the anchovy extract or the neochlorogenic acid is contained in an amount of 0.00 01 to 90% by weight based on the total weight of the composition.
The health functional food composition for preventing or improving obesity according to claim 1, wherein the anchovy extract or the neochlorogenic acid inhibits lipogenesis or reduces body fat.
The health functional food composition for preventing or improving obesity according to claim 1, wherein the anchovy extract or the neochlorogenic acid promotes energy metabolism and inhibits leptin and insulin secretion.
The method according to claim 1, wherein the health functional food has a formulation selected from the group consisting of powders, granules, tablets, capsules, pills, gels, jellies, suspensions, emulsions, syrups, tea bags, leaching teas and health drinks, Health functional food composition for preventing or improving obesity.
Anchovy ( Adenocaulon himalaicum Edgew.) extract; Or a health functional food composition for preventing or improving metabolic diseases comprising neochlorogenic acid represented by the following formula (1) or a food chemically acceptable salt thereof as an active ingredient:

[Formula 1]

.
The method according to claim 8, wherein the metabolic disease is one or more selected from the group consisting of fatty liver, diabetes, hypertension, hyperlipidemia, hypercholesterolemia, dyslipidemia, and arteriosclerosis, the functional food composition for preventing or improving metabolic disease .
Anchovy ( Adenocaulon himalaicum Edgew.) extract; Or a pharmaceutical composition for preventing or treating obesity comprising neochlorogenic acid represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient:

[Formula 1]

.
Anchovy ( Adenocaulon himalaicum Edgew.) extract; Or a pharmaceutical composition for preventing or treating metabolic diseases comprising neochlorogenic acid represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient:

[Formula 1]

.
The method according to claim 11, wherein the metabolic disease is at least one selected from the group consisting of fatty liver, diabetes, hypertension, hyperlipidemia, hypercholesterolemia, dyslipidemia, and arteriosclerosis, a pharmaceutical composition for preventing or treating metabolic diseases.
Anchovy ( Adenocaulon himalaicum Edgew.) extract; Or a cosmetic composition for preventing or improving cellulite comprising neochlorogenic acid or a cosmetically acceptable salt thereof represented by Formula 1 below as an active ingredient:

[Formula 1]

.
An effective amount of anchovy ( Adenocaulon himalaicum Edgew.) extract; Or a method for preventing, improving or treating obesity or metabolic disease comprising the step of administering neochlorogenic acid represented by Formula 1 or a food acceptable salt thereof to a subject in need thereof:

[Formula 1]

.
Anchovy ( Adenocaulon himalaicum Edgew.) extract; Or use of neochlorogenic acid represented by the following formula (1) or a pharmaceutically acceptable salt thereof for the preparation of a composition for preventing, improving or treating obesity or metabolic diseases:

[Formula 1]

.