KR102411895B1 - Composition for preventing or treating obesity and/or metabolic syndrome comprising Narcissus spp extracts - Google Patents

Abstract

The present invention relates to a composition for the prevention, improvement, and treatment of obesity and metabolic diseases, comprising a plant extract of the genus Narcissus, wherein the extract of the genus Narcissus has excellent human safety due to no skin irritation and cytotoxicity and inhibits the differentiation of adipocytes. and reduces the number of adipocytes, and can effectively inhibit the accumulation and excessive secretion of lipids, making it useful as a pharmaceutical composition, food composition, external preparation for skin and cosmetic composition for the prevention, improvement, and treatment of obesity and/or metabolic disease Available.

Description

Composition for preventing or treating obesity and/or metabolic syndrome comprising Narcissus spp extracts, comprising a plant extract of the genus Narcissus

The present invention relates to a composition for preventing, improving, and treating obesity and/or metabolic diseases, comprising a plant extract of the genus Narcissus, and the active ingredient of the present invention, a plant extract of the genus Narcissus, inhibits the differentiation of adipocytes to increase the number of adipocytes. Pharmaceutical, food, cosmetic, and external skin composition for the prevention, improvement, and treatment of obesity and metabolic diseases as a safe substance because it suppresses the increase and accumulation of lipids, suppresses excessive secretion of lipids from adipocytes, and does not cause skin irritation or cytotoxicity. useful as

Obesity is rapidly increasing worldwide, which is known to be a major cause of chronic diseases such as hypertension, hyperlipidemia, and diabetes. The World Health Organization has identified obesity as a new epidemic of the 21st century, and the global prevalence of obesity more than doubled between 1980 and 2014. Although the mortality rate due to obesity is increasing for most of the world's population, obesity is preventable (WHO, 2014). In Korea, 32.5% of adults are obese, and 2 out of 5 adult males and 1 in 4 adult females are obese, which is emerging as a serious problem threatening public health (Health and Nutrition Survey, 2014).

Obesity refers to a phenomenon in which excess calories are accumulated in the body in the form of fat by consuming excess calories compared to the calories consumed. According to the World Health Organization (WHO), about 400 million people in the world over the age of 15 are classified as obese and 1.6 billion people are overweight (published in September 2006). It is emerging as a serious social problem rather than a simple disease of Obesity is known to be caused by genetic influences, environmental influences due to westernized diets, and psychological influences due to stress, but the exact cause or mechanism has not been clearly elucidated.

There are two main goals of obesity treatment. The first is to reduce weight by burning excess fat, and the second is to improve metabolic imbalance. Abdominal obesity is closely related to symptoms such as insulin resistance, type 2 diabetes, hypertension and abnormal lipid metabolism, and acts as a strong risk factor for premature arteriosclerosis, ischemic heart disease and cerebrovascular disease (Kopleman P.G., Nature, 404, 2000; Manson et al., New England J. Med., 333, 1995; Must et al., JAMA, 282, 1999). Therefore, the current treatment for obesity aims not only to lose weight, but also to improve metabolic abnormalities by removing factors that induce cardiovascular disease at an early stage. Studies on the control of obesity through dietary intake control and energy consumption control are also being actively conducted. As an organ that controls the behavior of eating, the hypothalamus, motor, autonomic, and peripheral nervous systems are all involved. In the etiology of obesity, the central nervous system, especially the hypothalamus, plays an important role, and neuropeptide Y, POMC/CART, melanocytic Cortinic receptors, norepinephrine, and serotonin are representative factors secreted by the hypothalamus. Current strategies for developing anti-obesity drugs include reducing food intake, inhibiting calorie absorption, promoting exothermic response, regulating energy metabolism, and regulating signal transduction through the nervous system (Mijeong Park, Korean J Pediatr 48(2), 2005).

Among the obesity treatment drugs known so far, the most representative drugs include Xenical (Xenical ^TM , Roche Pharmaceuticals, Switzerland), Reductil ^TM , Abbott, USA), Exolise ^TM (Atopharma, France), etc., but heart disease , respiratory diseases, nervous system diseases, etc., along with side effects, and its efficacy is low, so the search for safer and more effective anti-obesity substances is in progress.

Fat stored in adipocytes is used as an important energy source in the body, but as obesity progresses, the number of adipocytes increases and adipocytes are differentiated. As adipocytes differentiate, the synthesis of triglycerides increases. It is known that triglycerides accumulated and stored in adipocytes increase the size of adipocytes, and their diameter can increase by about 20 times depending on the storage of fat, and as a result, the cell volume is known to increase up to several thousand times. Although the size of adipocytes can be controlled through diet control, the process of differentiation of new precursor adipocytes into adipocytes is ineffective. Therefore, in order to control the fundamental treatment or suppression of obesity, the differentiation process of adipocytes is It is important to control

On the other hand, Narcissus spp. plants are perennial grasses belonging to the family Narcissus, collectively called narcissus. Daffodils hibernate as bulbs in winter and flower mainly in spring. The bulbs of daffodils are poisonous, so they are used as an antiseptic for boils and sores, the flowers make perfume, and the scaly stems are used as a remedy for expectorant and whooping cough. Report that microniosomes including daffodil bulbs have wound healing effects by promoting proliferation and migration of fibroblasts (Ramaesh M et al., Daru 2018 Sep 12. doi:10.1007/s40199-018-0211-7 ) and anticancer (Rezadoost MH et al., Mol Biol Rep. 2019 46(5):5131-5142) effects are known. In addition, Korean Patent Laid-Open No. 10-2016-0114794 discloses that narcissus bulb extract has skin elasticity, wrinkle improvement, and skin irritation reduction effects, and Korean Patent Registration No. 10-1807978 discloses Narcissus that activates Sirt6. ), a peptide composition derived from the genus is disclosed. However, the efficacy of regulating adipocyte differentiation presented in the present invention has not yet been reported.

Accordingly, the present inventors were searching for substances with excellent anti-obesity and anti-fat effects and no side effects from natural products, and the narcissus plant extract inhibits the differentiation of adipocytes to control the number of adipocytes produced, and thus the accumulated excess By discharging energy, it was discovered that the anti-obesity effect was excellent, and the present invention was completed.

It is an object of the present invention to provide a pharmaceutical composition for preventing or treating obesity and/or metabolic disease, comprising a plant extract of the genus Narcissus.

Another object of the present invention is to provide a composition for external application for skin for preventing or treating obesity, comprising an extract of a plant of the genus Narcissus.

Another object of the present invention is to provide a food composition for the prevention or improvement of obesity and / or metabolic disease comprising a plant extract of the genus Narcissus.

Another object of the present invention is to provide a cosmetic composition for preventing or improving obesity comprising a plant extract of the genus Narcissus.

Another object of the present invention is to provide a method for preventing, improving, or treating obesity and/or metabolic disease using a composition comprising a plant extract of the genus Narcissus.

The present invention relates to a composition for preventing, improving, and treating obesity and/or metabolic disease, comprising an extract of a plant of the genus Narcissus as an active ingredient. More specifically, it relates to a pharmaceutical composition, a composition for external application for skin, a cosmetic composition, and a food composition comprising a plant extract of the genus Daffodil as an active ingredient, wherein the composition has excellent human safety due to no skin irritation and cytotoxicity, and It can inhibit differentiation, reduce the number of adipocytes, and effectively inhibit accumulation and excessive secretion of lipids.

In one aspect, the present invention provides a pharmaceutical composition for the prevention or treatment of obesity or metabolic disease comprising a plant extract of the genus Narcissus as an active ingredient.

In the present invention, the term "plant of the genus Narcissus (Narcissus spp.)" is a perennial plant of the Liliaceae family. The narcissus plants include Narcissus tazetta L. , Yellow daffodil ( Narcissus jonquilla L. ), narcissus ( Narcissus Pseudo-Narcissus L. ), and the like.

In the present invention, the term "extract" refers to a liquid component obtained by immersing a material including a target plant in various solvents, and then extracting and fractionating it for a certain period of time at room temperature or a warm state, and a solvent from the liquid component. It means a result such as solid content obtained by removing it. In addition, in addition to the result, it can be comprehensively interpreted as including all of the dilutions of the results, their concentrates, their preparations, and their purified products.

In the present invention, "Daffodil plant extract" is extracted from leaves, flowers, stems, roots, etc. of plants of the genus Narcissus, preferably flowers, leaves, and stems of plants of the genus Narcissus, more preferably, plants of the genus Narcissus. It is extracted from the above-ground part of the plant.

In the present invention, the plant extract of the genus Narcissus can be obtained by extraction with water or various organic solvents. In this case, the organic solvent used is not particularly limited thereto, as long as it can obtain an extract having an effect of inhibiting adipocyte differentiation and lipid accumulation in adipocytes or suppressing adipocyte-derived excessive secretion of lipids, but preferably water or a polar solvent. Or it may be a non-polar solvent. More preferably, water, a lower alcohol having 1 to 4 carbon atoms (ethanol, methanol, propanol or butanol, etc.), a mixed solvent thereof, etc. may be used, and most preferably water and ethanol may be used.

In addition, the method for obtaining the extract is also not particularly limited as long as it can obtain an extract having an effect of inhibiting adipocyte differentiation and lipid accumulation in adipocytes or suppressing adipocyte-derived excess secretion of lipids. The extraction method includes hot water extraction, cold extraction, ultrasonic extraction, or reflux cooling extraction method, and it is preferable to carry out the ultrasonic extraction method.

The ultrasonic extraction is a method of extracting useful components from various natural materials at room temperature by physical force rather than chemical force using a vibration element with a frequency of 20,000 or more per second, solvent extraction, vegetable oil extraction, or steam distillation extraction Unlike this, it has the advantage of being able to extract at a high concentration without destroying the active ingredients contained in natural materials at room temperature.

As a specific example, the ultrasonic extraction may be performed for 24 hours to 72 hours at room temperature using a 60% to 80% ethanol solution of the dried above-ground part of the plant of the genus Narcissus. Preferably, it is carried out for 36 hours to 60 hours at room temperature using a 65% to 75% ethanol solution, and more preferably, it is carried out for 48 hours at room temperature using a 70% ethanol solution. If it is outside the lower limit of the above numerical value, the active ingredient of the present invention contained in the above-ground part of the Daffodil plant is not sufficiently extracted. will decrease

As another specific example, the hot water extraction is performed by adding purified water to the above-ground powder of the dried daffodil plant at a high temperature, preferably 100 to 150 ° C, more preferably 100 to 130 ° C, even more preferably 110 to 130 ° C, Even more preferably, the reaction is carried out at 121° C. for 20 minutes to 1 hour, preferably 20 minutes to 50 minutes, more preferably 20 minutes to 40 minutes, and still more preferably 30 minutes.

The obtained narcissus plant extract is not limited thereto, but may be concentrated under reduced pressure using a vacuum concentrator or a vacuum rotary evaporator. In addition, after concentration under reduced pressure, but not limited thereto, it may be dried through freeze drying, reduced pressure drying, vacuum drying, boiling drying, or spray drying.

The narcissus plant extract, which is an active ingredient of the composition of the present invention, has the effect of inhibiting the differentiation of adipocytes, reducing the number of adipocytes, and inhibiting the accumulation and excessive secretion of lipids.

In a specific embodiment, the ethanol extract of the above-ground part of the narcissus plant inhibits the differentiation ability of adipocytes to suppress the increase in the number of adipocytes, and suppresses the degree of lipid production in adipocytes to suppress the accumulation of lipids and the secretion of lipids. The effect was confirmed (FIGS. 1 and 2).

Accordingly, the composition comprising the plant extract of the genus Daffodil of the present invention is used for prevention, improvement, and treatment of obesity and metabolic diseases due to effects such as inhibition of adipocyte differentiation, lipid accumulation in adipocytes, and suppression of excessive lipid secretion in adipocytes. useful as

As used herein, the term “obesity” refers to a state in which the number of adipocytes is above average and lipids are excessively accumulated in adipocytes.

As used herein, the term “metabolic disease” refers to a disease induced by or highly correlated with obesity. Examples thereof are not necessarily limited thereto, but may be any one selected from fatty liver, type 2 diabetes, hyperlipidemia, cardiovascular disease, arteriosclerosis, and lipid-related metabolic syndrome. In addition, the lipid-related metabolic syndrome refers to a disease in which several metabolic diseases such as diabetes and obesity appear simultaneously in one person.

The content of the narcissus plant extract contained in the composition is not particularly limited thereto, but is 0.00001 to 100% by weight, preferably 0.0001 to 15% by weight, more preferably 0.001 to 15% by weight, even more preferably based on the total weight of the composition. It may be included in an amount of 0.001 to 10% by weight.

As used herein, the term "pharmaceutical composition" refers to one prepared for the purpose of preventing or treating a disease, and each may be formulated in various forms according to a conventional method and used. For example, it can be formulated in oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, and diluents or excipients such as lubricants, wetting agents, flavoring agents, emulsifying agents, suspending agents, preservatives, surfactants, etc. It can be formulated and used as a parenteral formulation using In addition, it can be formulated and used in the form of external preparations, suppositories, external preparations for skin, and sterile injection solutions. As a specific example, the composition of the present invention may be used as an oral dosage form for oral administration. As another specific example, the composition of the present invention may be used by a method such as directly applying or dispersing to a region such as thigh, buttocks, or abdomen where a lot of fat cells are generally distributed. The application and dispersion are not limited to the above-mentioned area and may be applied to any area where adipocytes have developed.

In addition, according to each formulation, it can be prepared by further including a carrier known in the art, such as a pharmaceutically acceptable carrier, such as a buffer, an analgesic agent, a solubilizer, an isotonic agent, a stabilizer, a base, and the like.

As used herein, the term "pharmaceutically acceptable carrier" may refer to a carrier or diluent that does not inhibit the biological activity and properties of the injected active ingredient without stimulating the organism. The type of carrier usable in the present invention is not particularly limited, and any carrier commonly used in the art and pharmaceutically acceptable may be used. Non-limiting examples of the carrier include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and the like. These may be used alone or in mixture of two or more. The carrier may be a non-naturally occurring carrier.

The composition of the present invention can be administered in a pharmaceutically effective amount. The pharmaceutically effective amount means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment and not to cause side effects, and the effective dose level is determined by the patient's health condition, disease type, severity, The activity of the drug, the sensitivity to the drug, the administration method, administration time, administration route and excretion rate, treatment period, factors including drugs used in combination or concurrently, and other factors well known in the medical field may be determined according to factors. Specifically, it is generally 0.01 mg to 5000 mg per 1 kg of body weight of the administered subject, and may be administered in divided doses once or several times a day at regular time intervals according to the judgment of a doctor or pharmacist, but is not limited thereto.

In addition, the pharmaceutical composition of the present invention may be used alone or in combination with other pharmaceutically active compounds exhibiting an effect of preventing or treating obesity and/or metabolic diseases or in an appropriate group.

The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or may be administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. and may be administered single or multiple. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect with a minimum amount without causing side effects, and can be easily determined by those skilled in the art.

In one example, but not limited thereto, in addition to the pharmaceutical composition comprising the plant extract of the genus Daffodil of the present invention as an active ingredient, locasein, which acts on the central nervous system and reduces appetite through the activation of the appetite suppression center, is a non-central nervous system obesity treatment agent It can be used in combination with commonly used anti-obesity drugs such as orlistat, a fat absorption inhibitor, and liraglutide, an anti-obesity drug analog of GLP-1 (Glucagon-Like Peptide 1), an appetite regulator.

In the present invention, the term "administration" means introducing the pharmaceutical composition of the present invention to an individual by any suitable method, and the administration route of the composition of the present invention is oral or parenteral as long as it can reach the target tissue. It can be administered through

The method of administration of the pharmaceutical composition according to the present invention is not particularly limited, and may follow a method commonly used in the art. As a non-limiting example of the administration method, the composition may be administered by oral administration or parenteral administration. Specifically, the composition of the present invention can be used by a method such as directly applying or dispersing the composition to the thighs, buttocks, or abdomen where a lot of fat cells are generally distributed.

The pharmaceutical composition according to the present invention may be prepared in various dosage forms depending on the desired administration method.

The administration frequency of the composition of the present invention is not particularly limited thereto, but may be administered once a day or administered several times by dividing the dose.

As another aspect, the present invention provides a method for preventing or treating a lipid-related disease comprising administering a pharmaceutical composition comprising a plant extract of the genus Narcissus.

The narcissus plant extract and its preventive and therapeutic effects on obesity and metabolic diseases are the same as described above.

As used herein, the term “individual” may refer to any animal, including humans, that has or is likely to develop obesity and/or metabolic disease. The animal may be a mammal, such as a cow, a horse, a sheep, a pig, a goat, a camel, an antelope, a dog, or a cat, in need of treatment for symptoms similar to those of a human as well as humans, but is not limited thereto.

The prophylactic or therapeutic method of the present invention may include, specifically, administering the composition in a pharmaceutically effective amount to an individual who has or is at risk of developing obesity and/or metabolic disease. The method of administration is the same as described above.

The prevention may refer to any action of inhibiting or delaying the onset of obesity and/or metabolic disease by administering the composition for the prevention or treatment of obesity and/or metabolic disease according to the present invention to an individual.

In addition, the treatment may refer to any action of administering the composition of the present invention to a subject suspected of developing obesity and/or metabolic disease to improve or benefit from symptoms of obesity and/or metabolic disease.

The pharmaceutical composition comprising the plant extract of the genus Narcissus is as described above.

For administration, the composition of the present invention may include a pharmaceutically acceptable carrier, excipient or diluent in addition to the active ingredients described above. The carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

A suitable dosage of the composition of the present invention may vary depending on the patient's condition and weight, the degree of disease, drug form, and time, but may be appropriately selected by those skilled in the art. Specifically, the dosage of the above-ground part extract of the plant of the genus Narcissus may be 50 to 500 mg/Kg.

As another aspect, the present invention provides a composition for topical application for skin for preventing or treating obesity, comprising an extract of a plant of the genus Narcissus as an active ingredient.

The anti-obesity or therapeutic effect of the plant extract of the genus Narcissus is the same as described above.

The composition for external application for skin of the present invention can be used for the purpose of preventing and improving obesity, and the composition for external application for skin is generally used in areas such as thighs and buttocks where cellulite produced by hyperdifferentiation of fat and accumulation of lipids in fat cells is excessively distributed It can be applied to, and is not limited to the above region, and can be applied to any region where adipocytes have developed.

The composition for external application for skin according to the present invention may be formulated containing a cosmetically or dermatologically acceptable medium or base. These are all formulations suitable for topical application, for example, solutions, gels, solids, kneaded dry products, emulsions obtained by dispersing the oily phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules or, ionic (liposomes) and It may be provided in the form of a non-ionic vesicular dispersant, or in the form of a cream, skin, lotion, powder, ointment, spray, pack or concealer stick. It can also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant. These compositions can be prepared according to conventional methods in the art.

In addition, the composition for external application for skin according to the present invention is a fatty substance, an organic solvent, a solubilizer, a thickener, a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, water, an ionic type or nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or any other commonly used in cosmetics. It may contain adjuvants commonly used in the field of cosmetology or dermatology, such as ingredients. The adjuvant is introduced in an amount generally used in the field of cosmetology or dermatology.

The content of the narcissus plant extract contained in the composition is not particularly limited thereto, but is 0.00001 to 100% by weight, preferably 0.0001 to 15% by weight, more preferably 0.001 to 15% by weight, even more preferably based on the total weight of the composition. It may be included in an amount of 0.001 to 10% by weight.

As another aspect, the present invention provides a food composition for preventing or improving obesity and/or metabolic disease, comprising an above-ground part extract of a plant of the genus Narcissus as an active ingredient.

The narcissus plant extract and its effects for preventing and improving obesity and metabolic diseases are the same as described above.

In the present invention, “improving obesity” means suppressing, alleviating, or removing an increase in the number of adipocytes and excessive accumulation of lipids in adipocytes due to hyperdifferentiation of adipocytes in an individual.

In the present invention, "improvement of metabolic disease" means inhibiting, alleviating, or eliminating metabolic diseases caused by an increase in the number of adipocytes and excessive accumulation of lipids in adipocytes due to hyperdifferentiation of adipocytes in an individual.

When the composition of the present invention is used as a food additive, the plant extract of the genus Daffodil may be added as it is or may be used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment), and may further include a food pharmaceutically acceptable food supplement additive. Since the composition of the present invention uses an extract derived from a natural product as an active ingredient, there is no problem in terms of stability, so there is no big limitation on the amount of mixing.

The food composition of the present invention may include all foods in a conventional sense, and may be used interchangeably with terms known in the art, such as functional food and health functional food.

As used herein, the term "functional food" refers to food manufactured and processed using raw materials or ingredients useful for the human body according to Health Functional Food Act No. 6727, and "functionality" refers to the structure of the human body. And it means ingestion for the purpose of obtaining useful effects for health purposes such as regulating nutrients for function or physiological action.

In addition, the term "health functional food" as used in the present invention refers to a food manufactured and processed using a specific ingredient as a raw material or by extracting, concentrating, refining, or mixing a specific ingredient contained in the food raw material for the purpose of health supplementation, It refers to a food designed and processed to sufficiently exert biological control functions such as biological defense, regulation of biological rhythm, prevention and recovery of disease, etc., by the above ingredients, and the composition for health food is used for prevention of diseases and prevention of diseases. It can perform functions related to recovery, etc.

There is no limitation on the type of food in which the composition of the present invention can be used for the prevention or improvement of obesity and/or metabolic disease. In addition, the composition comprising the plant extract of the genus Daffodil of the present invention as an active ingredient can be prepared by mixing other suitable auxiliary ingredients that may be contained in food and known additives according to the selection of those skilled in the art. Examples of foods that can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and There are vitamin complexes and the like, and it can be prepared by adding the extract according to the present invention and a fraction thereof as a main component to juice, tea, jelly, juice, and the like.

In addition, foods that can be applied to the present invention include, for example, special nutritional foods (eg, formula milk, infant food, etc.), processed meat products, fish meat products, tofu, jelly, noodles (eg, ramen, noodles, etc.), health supplements , Seasoned foods (eg soy sauce, soybean paste, red pepper paste, mixed soy sauce, etc.), sauces, sweets (eg snacks), dairy products (eg fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchi, pickles, etc.) ), beverages (eg, fruit, vegetable beverages, soy milk, fermented beverages, etc.), and natural seasonings (eg, ramen soup, etc.).

The content of the narcissus plant extract contained in the composition is not particularly limited thereto, but is 0.00001 to 100% by weight, preferably 0.0001 to 15% by weight, more preferably 0.001 to 15% by weight, even more preferably based on the total weight of the composition. It may be included in an amount of 0.001 to 10% by weight.

When the health functional food composition of the present invention is used in the form of a beverage, it may contain various sweetening agents, flavoring agents, or natural carbohydrates as additional ingredients, as in a conventional beverage. In addition to the above, the health functional food composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin , alcohol, a carbonation agent used in carbonated beverages, and the like. In addition, it may contain the pulp for the production of natural fruit juice, fruit juice beverage and vegetable beverage.

As another aspect, the present invention provides a cosmetic composition for preventing and improving obesity, comprising a plant extract of the genus Narcissus.

The narcissus plant extract and its anti-obesity prevention and improvement effects are the same as described above.

The cosmetic composition of the present invention can be used for the purpose of preventing and improving obesity, and the cosmetic composition is generally applied to areas such as thighs and buttocks where cellulite produced by hyperdifferentiation of fat and accumulation of lipids in adipocytes is excessively distributed. It may be applied to any region where adipocytes have developed without being limited only to the above region.

In the present invention, the ingredients included in the "cosmetic composition" may include ingredients commonly used in cosmetic compositions in addition to the active ingredient as an active ingredient, for example, antioxidants, stabilizers, solubilizers, vitamins, pigments and customary adjuvants such as perfumes, and carriers. The cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing , oil, powder foundation, emulsion foundation, wax foundation, pack, massage cream, spray, etc., but is not limited thereto. More specifically, it may be prepared in the form of a flexible lotion, a nourishing lotion, a nourishing cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray, or a powder.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. can

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylglycol oil, glycerol fatty ester, polyethylene glycol or fatty acid ester of sorbitan.

When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, and microcrystals Adult cellulose, aluminum metahydroxide, bentonite, agar or tracanth may be used.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In particular, in the case of a spray, additional chlorofluorohydrocarbon, propane /may contain propellants such as butane or dimethyl ether.

When the formulation of the present invention is a surfactant-containing cleansing agent, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide ether as carrier components Sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative or ethoxylated glycerol fatty acid ester may be used.

When the cosmetic composition of the present invention is a soap, a surfactant-containing cleansing formulation, or a surfactant-free cleansing formulation, it may be applied to the skin and then wiped off, removed, or washed off with water. As a specific example, the soap is liquid soap, powder soap, solid soap, and oil soap, the surfactant-containing cleansing formulation is a cleansing foam, cleansing water, cleansing towel, and cleansing pack, and the surfactant-free cleansing formulation is a cleansing cream , cleansing lotion, cleansing water, and cleansing gel, but not limited thereto.

The content of the narcissus plant extract contained in the composition is not particularly limited thereto, but is 0.00001 to 100% by weight, preferably 0.0001 to 15% by weight, more preferably 0.001 to 15% by weight, even more preferably based on the total weight of the composition. It may be included in an amount of 0.001 to 10% by weight.

The above-mentioned composition containing the plant extract of the genus Daffodil of the present invention is made from natural medicinal plants, so even when used as a pharmaceutical composition, a food composition, a composition for external application for the skin, or a cosmetic composition, side effects may be less than that of a general synthetic compound, so it is safely contained It can be useful.

Daffodil plant extract, which is the active ingredient of the present invention, has excellent human safety due to no skin irritation and cytotoxicity, while inhibiting the differentiation of adipocytes, reducing the number of adipocytes, and effectively inhibiting the accumulation and excessive secretion of lipids. It can be usefully used as a pharmaceutical composition, a food composition, a composition for external application to the skin, and a cosmetic composition for the prevention, improvement, and treatment of obesity and/or metabolic diseases. In particular, it can be effectively applied for the purpose of suppressing the accumulation and excessive secretion of lipids in areas where fat cells are developed, including areas such as thighs and buttocks where cellulite generated by hyperdifferentiation of fat is excessively distributed.

1 is a result of observation of the effect of inhibiting adipocyte differentiation of 3T3L1 preadipocytes by the extracts of narcissus, yellow daffodil, and morning daffodils according to an embodiment of the present invention by using Oil-red O staining method.
2 is a numerical result of the inhibitory effect on adipocyte differentiation of 3T3L1 preadipocytes by extracts of daffodils, yellow daffodils and trumpet daffodils according to an embodiment of the present invention.
3 is a numerical result of the lipolysis promoting effect of 3T3L1 cells differentiated into adipocytes by extracts of daffodils, yellow daffodils, and morning daffodils according to an embodiment of the present invention.
4 is a result of measuring the inhibitory effect of tri-glyceride accumulation in 3T3L1 preadipocytes by extracts of daffodils, yellow daffodils, and morning daffodils according to an embodiment of the present invention.

Hereinafter, examples and the like will be described in detail to help the understanding of the present invention. However, the embodiments according to the present invention may be modified in various other forms, and the scope of the present invention should not be construed as being limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those of ordinary skill in the art.

Example 1: Preparation of extracts from plants of the genus Narcissus

Narcissus tazetta L. ), yellow daffodil ( Narcissus jonquilla L. ), and morning daffodil ( Narcissus Pseudo-Narcissus L. ) After cleaning the above-ground parts of plants, dry them in the shade at 20°C to 35°C, and then the particle size is 1 It pulverized so that it might become mm or less. After that, 100 g of the ground powder of the above-ground part of the daffodil plant was immersed in a 70% ethanol solvent, followed by ultrasonic extraction for 48 hours, and the resulting extract was filtered using filter paper (Advantec, No. 2). The filtrate was concentrated under reduced pressure to prepare an ethanol extract of an above-ground part of daffodils.

Example 2. Inhibitory effect on adipocyte differentiation of Narcissus plant extract

In order to investigate the effect of the plant extract of Narcissus on the inhibition of adipocyte differentiation, the following experiment was conducted.

Specifically, adipocytes (3T3-L1) were purchased from ATCC (American Tissue Culture Collection, USA) and cultured in DMEM medium supplemented with 10% BCS (Bovine Calf Serum). In order to differentiate into adipocytes, 1×10 ⁵ cells per well were inoculated in a 6-well plate with DMEM medium containing 10% BCS, and then the cells were confluent in the wells at 5% CO ₂ and 37°C. Incubated until fully grown. After that, it was further cultured for 2 days, and MDI (isobutylmethylxanthin 0.5 mM, dexamethason 1 μM , insulin 1 μg/mL) cocktail was treated. After 3 days, it was replaced with a medium containing insulin (insulin 1 μg/mL), and again after 3 days, it was replaced with a DMEM medium containing 10% FBS. Samples were treated together from the point of inducing differentiation by treatment with MDI cocktail, and then re-treated at the same concentration each time the culture medium was replaced. The amount of fat accumulated in the differentiated cells was stained by Oil Red O staining, dissolved with isopropyl alcohol, and absorbance (Optical Density) was measured at 540 nm.

As a result, as can be seen in FIGS. 1 and 2, when the immature adipocytes 3T3-L1 were treated with MDI, differentiation into adipocytes was induced and it was confirmed that intracellular lipids were accumulated. By inhibiting the differentiation into adipocytes, it was confirmed that intracellular lipids did not accumulate.

Example 3. Effect of lipolysis promoting effect of plant extracts of the genus Narcissus

As in Example 2, immature adipocytes 3T3-L1 were treated with MDI to induce differentiation into adipocytes. Samples were treated for each concentration in DMEM medium containing 10% FBS after differentiation induction for 9 days. The amount of fat accumulated in the differentiated cells was stained by Oil Red O staining, dissolved with isopropyl alcohol, and optical density was measured at 540 nm and then quantified.

As a result, as can be seen in FIG. 3 , it was confirmed that the concentration-dependently concentration-dependent decomposition of the fat accumulated in adipocytes of the plant extract of the genus Daffodil was promoted.

Example 4. Inhibitory effect of triglyceride triglyceride of plant extract of the genus Narcissus

As in Example 2, immature adipocytes 3T3-L1 were treated with MDI to induce differentiation into adipocytes, and then the produced triglyceride was measured using a triglyceride determination kit (Sigma, USA).

As a result, as can be seen in FIG. 4 , it was confirmed that the amount of neutral lipids decreased in a concentration-dependent manner in the group treated with the plant extract of the genus Narcissus.

Example 5: Safety confirmation experiment on human skin of Narcissus plant extract

5-1. Preparation of external preparations for skin including extracts from plants of the genus Daffodil

As described above, in order to confirm that the plant extract of the genus Narcissus, which was found to be excellent in inhibiting adipocyte lipid production, is safe for human skin, an external preparation for skin containing the plant extract of the genus Narcissus was prepared and a skin safety verification experiment was performed.

An external preparation for skin containing a plant extract of the genus Narcissus was prepared with the content of ingredients shown in Table 1 below.

For the preparation of external preparations for skin, purified water, glycerin, and butylene glycol were mixed and dissolved at 70 ° C. (aqueous part), and the remaining components except for the three components and trimethanolamine were dissolved at 70 ° C (oil phase part). The oil part was added to the water part, and the mixture was first emulsified by stirring with a homomixer (Tokushu Kika, Japan), and trimethanolamine was finally added thereto. After removing the bubbles generated in the mixed solution, the mixture was cooled to room temperature to prepare an external preparation for skin.

ingredient content (%) control test group Purified water 72 71 glycerin 8.0 8.0 butylene glycol 4.0 4.0 Narcissus Plant Extract 0 1.0 Caprylic Capri Triglyceride 8.0 8.0 squalane 5.0 5.0 Cetearyl Glucuside 1.5 1.5 Sorbitan Stearate 0.4 0.4 cetearyl alcohol 1.0 1.0 trimethanolamine 0.1 0.1 gross weight 100 100

5-2. skin irritation test

Whether the narcissus plant extract stimulates the skin by performing a total of 9 24-hour cumulative patches every other day on the upper forearm on 30 healthy adults using each external preparation for skin prepared in Example 5-1 was measured.

The patching method used a pin chamber (Finn chamber, Epitest Ltd, Finland). After 15ul of each of the external preparations for skin were dropped into the chamber, patching was performed. The degree of reaction shown on the skin each time was scored using the following formula, and the results are shown in Table 2 below.

[Empirical Formula 1]

Average reactivity = [[response index × reactivity / total number of subjects × highest score (4 points)] × 100 ] ÷ number of tests (9 times)

At this time, in the reactivity, ± is given a score of 1 point, + is 2 points, and ++ is 4 points, and when the average reactivity is less than 3, it was judged as a safe composition.

test substance Number of subjects who responded average reactivity 1 week 2 weeks 3 weeks Primary Secondary tertiary 4th 5th 6th 7th 8th 9th ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ control - - - - - - - - - - - - - - - - - - - - - - - - - - - 0.00 test group One - - One - - - - - - - - - - - - - - - - - - - - - - - 0.13 number of people tested 30 30 30 30 30 30 30 30 30

In the case of the test group in Table 2, the number of persons corresponding to ± , +, and ++ was 1, 0, and 0, respectively, and the rest did not respond. When calculated according to the above-described formula, [(1×2)/(20×4)]×100/9=0.13, with an average reactivity of 0.13, so it was 3 or less, and it was judged to be a safe composition.

As shown in Table 2, the external skin preparations containing the plant extract of the genus Daffodil (test group) did not show a clear cumulative irritation pattern and were judged to be safe substances for human skin.

Preparation Example 1: Cosmetic formulation

Preparation Example 1-1: Softening lotion

As shown in Table 3 below, a softening lotion containing a plant extract of the genus Narcissus as an active ingredient was prepared according to a conventional method.

ingredient weight% Narcissus Plant Extract 0.01 glycerin 3.0 butylene glycol 2.0 propylene glycol 2.0 carboxyvinyl polymer 0.1 ethanol 10.0 triethanolamine 0.1 Preservatives, trace colors, trace fragrances and trace purified water 82.79 sum 100.0

Preparation Example 1-2: Nutrient lotion

Nutrient lotion containing Narcissus extract as an active ingredient was prepared according to a conventional method as shown in Table 4 below.

ingredient weight% Narcissus Plant Extract 0.01 beeswax 4.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.5 liquid paraffin 5.0 squalane 5.0 Caprylic/Capric Triglycerides 5.0 glycerin 3.0 butylene glycol 3.0 propylene glycol 3.0 carboxyvinyl polymer 0.1 triethanolamine 0.2 Preservatives, micro pigments, micro fragrances and micro-purified water 69.69 sum 100.0

Preparation Example 1-3: Nourishing Cream

As shown in Table 5 below, a nourishing cream containing an extract of the genus Narcissus as an active ingredient was prepared according to a conventional method.

ingredient weight% Narcissus Plant Extract 0.01 beeswax 10.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.5 liquid paraffin 10.0 squalane 5.0 Caprylic/Capric Triglycerides 5.0 glycerin 5.0 butylene glycol 3.0 propylene glycol 3.0 triethanolamine 0.2 Preservatives, micro pigments, micro fragrances and micro-purified water 56.79 sum 100.0

Preparation Example 1-4: Massage Cream

As shown in Table 6 below, a nourishing cream containing an extract of the genus Narcissus as an active ingredient was prepared according to a conventional method.

ingredient weight% Narcissus Plant Extract 0.01 beeswax 10.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.8 liquid paraffin 40.0 squalane 5.0 Caprylic/Capric Triglycerides 4.0 glycerin 5.0 butylene glycol 3.0 propylene glycol 3.0 triethanolamine 0.2 Preservatives, micro pigments, micro fragrances and micro-purified water 27.49 sum 100.0

Preparation Example 1-5: Pack

As shown in Table 7 below, a pack containing an extract of the genus Narcissus as an active ingredient was prepared according to a conventional method.

ingredient weight% Narcissus Plant Extract 0.01 polyvinyl alcohol 13.0 Sodium Carboxymethylcellulose 0.2 allantoin 0.1 ethanol 5.0 nonylphenyl ether 0.3 Preservatives, micro pigments, micro fragrances and micro-purified water 81.39 sum 100.0

Preparation Example 2: Pharmaceutical formulation

Preparation Example 2-1: Preparation of powder

ingredient content (g) Narcissus Plant Extract 2 lactose One

The above ingredients were mixed and filled in an airtight cloth to prepare a powder.

Preparation Example 2-2: Preparation of tablets

ingredient Content (mg) Narcissus Plant Extract 100 corn starch 100 lactose 100 Magnesium Stearate 2

After mixing the above ingredients, tablets were prepared by tableting according to a conventional manufacturing method of tablets.

Preparation 2-3: Preparation of capsules

ingredient Content (mg) Narcissus Plant Extract 100 corn starch 100 lactose 100 Magnesium Stearate 2

After mixing the above ingredients, the capsules were prepared by filling in gelatin capsules according to a conventional manufacturing method of capsules.

Preparation Example 2-4: Preparation of gel

ingredient weight% Narcissus Plant Extract 1.00 Butylene Glycol 2.00 glycerin 1.00 Disodium EDIT 0.02 PEG-60 Hydrogenated Castor Oil 1.00 Cocamidopropyl Betaine 4.00 Lauryl Glucoside 6.00 Polysorbate 20 1.00 Sodium Benzoate 0.40 caprylic glycol 0.20 sodium lactate 0.50 Hydroxyethyl Cellulose 0.7 Purified water 82.18 sum 100.0

After mixing the above ingredients, a gel containing Narcissus extract as an active ingredient was prepared according to a conventional method.

Preparation Example 2-5: Preparation of ointment

ingredient weight% Narcissus Plant Extract 1.0 diethanolamine 1.5 polyvinylptolidone 5.0 propylene glycol 30.0 Purified water 62.5 sum 100.0

Preparation Example 3: Preparation of food

Preparation Example 3-1: Preparation of wheat flour food

0.5 to 5.0 parts by weight of the plant extract of the genus Daffodil of the present invention was added to wheat flour, and breads, cakes, cookies, crackers and noodles were prepared using this mixture.

Preparation Example 3-2: Preparation of soups and gravies

By adding 0.1 to 5.0 parts by weight of the plant extract of the genus Daffodil of the present invention to soup and broth, processed meat products for health promotion, soup and broth of noodles were prepared.

Preparation 3-3: Preparation of ground beef

Ground beef for health promotion was prepared by adding 10 parts by weight of the plant extract of the genus Narcissus of the present invention to ground beef.

Preparation 3-4: Preparation of dairy products

5-10 parts by weight of the plant extract of the genus Narcissus of the present invention was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.

Preparation 3-5: Preparation of Sausage

A sausage food composition comprising the plant extract of the genus Narcissus of the present invention was prepared as follows. 65.18% by weight of pork, 25% by weight of chicken meat, 3.5% by weight of starch, 1.7% by weight of soybean protein, 1.62% by weight of salt, 1.4% by weight of glucose and 1.5% by weight of glycerin, and 0.1% by weight of narcissus plant extract were mixed in a conventional manner Sausage was prepared.

Preparation Example 3-6: Preparation of health drinks

Instant sterilization by homogeneously mixing 5 g of the plant extract of the genus Daffodil of the present invention with subsidiary materials such as high fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%), and water (75%) After this, it was prepared by packaging it in a small packaging container such as a glass bottle or a plastic bottle.

Preparation Example 3-7: Preparation of vegetable juice

Vegetable juice was prepared by adding 5 g of the plant extract of the genus Narcissus of the present invention to 1,000 ml of tomato or carrot juice.

Preparation 3-8: Preparation of fruit juice

Fruit juice was prepared by adding 1 g of the plant extract of the genus Narcissus of the present invention to 1,000 ml of apple or grape juice.

Claims (8)

Narcissus tazetta L. ), yellow daffodil ( Narcissus jonquilla L. ) and morning daffodil ( Narcissus Pseudo-Narcissus L. ) comprising an above-ground extract of plants of the genus Narcissus selected from the group consisting of an active ingredient A pharmaceutical composition for preventing or treating obesity or hyperlipidemia.
delete Daffodil ( Narcissus tazetta L. ), yellow daffodil ( Narcissus jonquilla L. ) and morning daffodil ( Narcissus Pseudo-Narcissus L. ) Obesity or hyperlipidemia comprising an above-ground extract of a plant of the genus Narcissus as an active ingredient Food composition for prevention or improvement.
delete Narcissus tazetta L. ), yellow daffodil ( Narcissus jonquilla L. ), and morning daffodil ( Narcissus Pseudo-Narcissus L. ) Prevention of obesity comprising an above-ground extract of a plant of the genus Narcissus as an active ingredient Or a composition for external application for skin improvement.
[Claim 6] The composition for external application for skin according to claim 5, wherein the composition is applied to an internal part of an individual where cellulite is formed due to hyperdifferentiation of adipocytes and accumulation of lipids in adipocytes.
Narcissus tazetta L. ), yellow daffodil ( Narcissus jonquilla L. ), and morning daffodil ( Narcissus Pseudo-Narcissus L. ) Prevention of obesity comprising an above-ground extract of a plant of the genus Narcissus as an active ingredient Or cosmetic composition for improvement.
8. The cosmetic composition according to claim 7, wherein the composition is applied to an area inside an individual where cellulite is formed due to hyperdifferentiation of adipocytes and accumulation of lipids in adipocytes.

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