JP7217550B2 - Composition containing black ginger - Google Patents

Description

The present invention relates to a composition containing black ginger and specific components and having a UCP1 expression promoting effect and/or a brown adipocyte differentiation promoting effect.

Uncoupling proteins (UCPs) have the function of uncoupling oxidative phosphorylation reactions in the inner mitochondrial membrane and dissipating energy as heat (see Non-Patent Document 1). In particular, UCP1 is specifically expressed in brown adipocytes, which is the site of heat production, and plays a role in directly consuming energy by converting neutral lipids into heat without ATP synthesis in the electron transport system. bear. In addition, if differentiation from progenitor cells to brown adipocytes can be promoted, the expression level of UCP1 can be increased, and neutral lipids can be converted into heat. Therefore, if UCP1 expression level or brown adipocyte differentiation can be promoted, obesity may be eliminated through consumption of neutral lipids. Regarding such brown adipocyte differentiation promoters and UCP1 expression promoters, Patent Document 1 describes those containing catechins as active ingredients.

JP 2014-65672 A

Proceedings of the 124th Japan Medical Association Symposium, p. 62-70

The drug capable of promoting the expression level and activation of UCP1 described in Patent Document 1 contains, as an active ingredient, a specific substance isolated and purified from a natural product. However, since such a specific substance has a strong pharmacological action, it is necessary to be careful when ingesting it, and there is a risk of side effects caused by excessive ingestion.

The present invention has been made in view of such circumstances, has no side effects, can be ingested for a long period of time, and exhibits a UCP1 expression promoting effect and/or brown adipocyte differentiation promoting effect. The problem to be solved by the invention is to provide a product.

The present inventors have made intensive studies to solve the above problems, and surprisingly, by combining black ginger and specific ingredients, synergistic rather than additive effects of promoting UCP1 expression and / Or it was found that an effect of promoting brown adipocyte differentiation can be obtained. Then, creation of a composition containing black ginger and specific components as a composition for promoting UCP1 expression, a composition for promoting metabolism, an anti-obesity composition, a composition for reducing body fat, and a composition for promoting heat production. succeeded in. The present invention is an invention completed based on such knowledge and successful examples.

Therefore, according to the present invention, it contains black ginger (Kaempferia parviflora) and at least one component selected from the group consisting of hops, ketsumeishi, melilot, ginger, elastin, gallic acid, caffeine, oligosaccharides and amino acids. Provided is a cosmetic composition for

Provided is a composition for promoting UCP1 expression containing black ginger and at least one component selected from the group consisting of hops, ketsumeishi, melilot, ginger, elastin, gallic acid, caffeine, oligosaccharides and amino acids.

According to another aspect of the present invention, a brown ginger containing black ginger and at least one component selected from the group consisting of hops, ketsumeishi, melilot, ginger, elastin, gallic acid, caffeine, oligosaccharides and amino acids A composition for activating adipocytes is provided.

According to another aspect of the present invention, a metabolism containing black ginger and at least one component selected from the group consisting of hops, ketsumeishi, melilot, ginger, elastin, gallic acid, caffeine, oligosaccharides and amino acids A promotional composition is provided.

According to another aspect of the present invention, an antioxidant containing black ginger and at least one component selected from the group consisting of hops, ketsumeishi, melilot, ginger, elastin, gallic acid, caffeine, oligosaccharides and amino acids A composition for obesity is provided.

According to another aspect of the present invention, a body containing black ginger and at least one component selected from the group consisting of hops, ketsumeishi, melilot, ginger, elastin, gallic acid, caffeine, oligosaccharides and amino acids Compositions for fat reduction are provided.

According to another aspect of the present invention, heat containing black ginger and at least one component selected from the group consisting of hops, ketsumeishi, melilot, ginger, elastin, gallic acid, caffeine, oligosaccharides and amino acids A composition for promoting production is provided.

According to another aspect of the present invention, a composition containing black ginger and at least one component selected from the group consisting of hops, ketsumeishi, melilot, ginger, elastin, gallic acid, caffeine, oligosaccharides and amino acids. goods are provided.

Preferably, the composition of the present invention has brown adipocyte activation action, metabolism promotion action, anti-obesity action, body fat reduction action, heat production promotion action, UCP1 expression promotion action, energy production promotion action, neutral lipid lowering action , sebum-suppressing action and fat-metabolism-promoting action.

Preferably, in the composition of the present invention, the oligosaccharide is at least one oligosaccharide selected from the group consisting of isomaltooligosaccharide, fructo-oligosaccharide and milk-fruit oligosaccharide.

Preferably, in the composition of the present invention, the amino acid is at least one amino acid selected from the group consisting of alanine, arginine and serine.

The composition of the present invention has UCP1 expression promoting action and / or brown adipocyte differentiation promoting action, and further related to these actions, brown adipocyte activation action, metabolism promotion action, anti-obesity action, body fat It can be expected to show reduction action, heat production promotion action, UCP1 expression promotion action, energy production promotion action, neutral lipid lowering action, sebum suppression action, fat metabolism promotion action, and the like.

Since the black ginger and specific ingredients used in the composition of the present invention have been used in pharmaceuticals and cosmetics, the composition of the present invention is highly safe. Therefore, the composition of the present invention is useful as a composition for promoting UCP1 expression, a composition for promoting metabolism, an anti-obesity composition, a composition for reducing body fat, and a composition for promoting heat production, by having the above effects. and can be expected to be provided in parenteral or oral form.

FIG. 1 is a diagram showing the sensory evaluation results of a test substance (isomalto-oligosaccharide) and a combination of a black ginger extract and a test substance, based on black ginger extract, as described in Examples. . FIG. 2 is a diagram showing the sensory evaluation results of the test substance (fructo-oligosaccharide) and the combination of the black ginger extract and the test substance, based on the black ginger extract, as described in the Examples. FIG. 3 is a diagram showing the sensory evaluation results of the test substance (milk oligosaccharide) and the combination of the black ginger extract and the test substance, based on the black ginger extract, as described in the Examples. be. FIG. 4 is a diagram showing the sensory evaluation results of the test substance (alanine) and the combination of the black ginger extract and the test substance, based on the black ginger extract, as described in the Examples. FIG. 5 is a diagram showing the sensory evaluation results of the test substance (serine) and the combination of the black ginger extract and the test substance, based on the black ginger extract, as described in Examples.

The present invention will be described in detail below.
The composition of the present invention has a UCP1 expression promoting action and / or brown adipocyte differentiation promoting action, and includes black ginger (Kaempferia parviflora), hops, ketsumeishi, melilot, ginger, elastin, gallic acid, caffeine, It contains at least one component of oligosaccharide and amino acid (hereinafter referred to as specific component).

The composition of the present invention may have any one of the UCP1 expression promoting action and brown adipocyte differentiation promoting action, or may have both of these two actions. good. Moreover, the specific component to be combined with black ginger may be one of the specific components, or may be two or more components. For example, combinations such as caffeine, alanine and isomalto-oligosaccharides among the specified ingredients are possible.

In addition to UCP1 expression promoting action and brown adipocyte differentiation promoting action, the composition of the present invention has brown adipocyte activation action, metabolism promotion action, anti-obesity action, body fat reduction action, heat production promotion action, energy production promotion action, neutral lipid lowering action, sebum suppressing action and fat metabolism promoting action.

Since the composition of the present invention has the above-described action, it can be used as a composition for promoting UCP1 expression, a composition for promoting metabolism, an anti-obesity composition, a composition for reducing body fat, and a composition for promoting heat production. can be harvested

Black ginger (Kaempferia parviflora) is a plant belonging to the genus Zingiberaceae, which is known to grow naturally in Southeast Asia and the like. Black ginger is known to have effects such as increasing energy, tonic, lowering blood sugar level, recovering physical strength, improving the digestive system, improving vaginal discharge, hemorrhoids, hemorrhoids, nausea, stomatitis, arthralgia, and stomachache. It is Black ginger is a natural plant that has been ingested by humans for a long time and is highly safe. It can be applied to various uses in oral or oral form.

The part of black ginger to be used is not particularly limited as long as it contains a component that contributes to the desired pharmacological action. It is a rhizome rich in polymethoxyflavonoids (PMF) such as flavone (57DMF).

In addition to unprocessed black ginger, for example, processed products (dried product, cut product, etc.), black ginger or processed black ginger powder, squeezed juice, extract, etc. contain things. Here, the extract is not particularly limited as long as the components of black ginger are extracted, but for example, an extract obtained by extracting black ginger or its processed product with a solvent, its diluted solution or concentrated solution , or their dried products and their powders. The black ginger used in the present invention is an extract such as an extract or juice of black ginger, or the A dried extract is preferred.

Black ginger powder is obtained, for example, by drying sliced black ginger after washing in the sun or using a drier, as it is, or by cutting it into an appropriate shape and size, and grinding it with a pulverizer. It can be obtained by grinding. Commonly used pulverizers can be widely used, and for example, a pulverizer composed of a raw material hopper, a pulverizer, a classifier, a product holder and the like can be used.

A black ginger extract is obtained by extracting black ginger or a processed product thereof with a solvent. Solvents used for extraction include, for example, lower alcohols such as ethanol, methanol, isopropanol and butanol; lower esters such as ethyl acetate and methyl acetate; acetone; and mixed solvents of these with water. Water is also included as an extraction solvent, and may be hot water, hot water, or the like. Since the composition of the present invention can be orally ingested by humans, the extract of black ginger, which is a raw material, can be either water alone, ethanol alone, or a mixed solvent of water and ethanol (so-called water-containing It is preferably extracted with ethanol). In particular, it is preferable to use water-containing ethanol with a concentration of 20 to 80 vol % as the solvent, and it is more preferable to use water-containing ethanol with a concentration of 40 to 70 vol % as the solvent.

When a mixed solvent is used as the solvent, for example, acetone/water (2/8 to 8/2, volume ratio) mixture, ethanol/water (2/8 to 8/2, volume ratio) mixture, etc. can be used. can. In the case of ethanol/water, it is preferable to add a solvent of 2 to 20 times the mass of the rhizome of black ginger and extract the mixture at room temperature or under heating for about 10 minutes to 48 hours.

The extraction method is not particularly limited, but, for example, from the viewpoint of safety, convenience and industrialization, it is preferable to perform the extraction operation under as mild conditions as possible. For example, the part of black ginger or its dried product is pulverized, crushed, shredded, etc., added with a solvent of 2 to 20 times the mass, and heated at a temperature in the range of 0 ° C. to the reflux temperature of the solvent for 10 minutes to 48 hours. Extraction is performed under arbitrary conditions such as standing, shaking, stirring, and reflux. After extraction, a solid-liquid separation operation such as filtration or centrifugation is performed to remove insoluble solids. An extract is obtained by performing operations such as dilution and concentration as necessary. Furthermore, the same operation may be repeated for extraction of insoluble matter, and the resulting extract may be used in combination with the previous extract. These extracts may be used after further purification by a purification method commonly used by those skilled in the art.

The obtained extract can be used as it is or after concentration, for example, in the form of a liquid, a concentrate, or a dried product obtained by drying these. Drying is not particularly limited, and can be carried out by methods commonly used by those skilled in the art, such as spray drying, freeze drying, vacuum drying, and fluidized drying. Furthermore, the dried product obtained by the above method can be used after pulverizing using a method known to those skilled in the art.

The black ginger extract used in the composition of the present invention is not particularly limited. %, more preferably 0.5 to 20 wt%. In addition, the ratio of the amount of PMF (total amount of 57DMF, 3,5,7,4'-tetramethoxyflavone and 3,5,7,3',4'-pentamethoxyflavone) to the total amount of extract (total PMF content) is It is preferably 0.01 to 50 wt%, more preferably 0.1 to 30 wt%, even more preferably 0.5 to 20 wt%.

In addition to the above black ginger, the composition of the present invention contains one or more specific components selected from hops, ketsumeishi, melilot, ginger, elastin, gallic acid, caffeine, oligosaccharides and amino acids. . Among the above oligosaccharides, isomalto-oligosaccharides, fructo-oligosaccharides and milk-fruit oligosaccharides are preferable. The amino acids are preferably amino acids other than glutamic acid and methionine, more preferably amino acids other than acidic amino acids and sulfur-containing amino acids, and even more preferably alanine, arginine and serine.

Specific components are not particularly limited as long as they are generally known. For example, among oligosaccharides, isomalto-oligosaccharides, fructo-oligosaccharides and milk oligosaccharides are commonly known saccharides, and these can be combined with black ginger in the form of solids, liquids, etc. . In addition, among the amino acids, alanine, arginine and serine are commonly known amino acids, and may be either D- or L-form, and the shape is not particularly limited, but the solid L-form is preferred. .

Similarly, hops, ketsumeishi, melilot, ginger, elastin, gallic acid, and caffeine are not particularly limited as long as they are commonly known. Moreover, among these, with regard to the specific component which is a natural product, the part used may be a part or the whole of them.

Among the specific ingredients, natural products such as hops, ketsumeishi, melilot and ginger are not particularly limited as long as they are generally known. For example, hops are known as Humulus lupulus (scientific name: Humulus lupulus), and for example, parts such as its flowers (cones), seeds, fruits, stems and leaves, roots, etc. can be used, but cones can be used. preferable. Ketsumeishi is the seed of Senna obtusifolia (scientific name: Senna obtusifolia). Melilot is known as Melilotus officinalis (Scientific name: Melilotus officinalis). For example, parts such as flowers, seeds, fruits, stems and leaves, and roots thereof can be used, but the flowers or stems and leaves are preferably used. Ginger is known as ginger (scientific name: Zingiber officinale), and its parts such as flowers, seeds, fruits, stems and leaves, and roots (rhizome) can be used, but rhizomes are preferably used.

The specific component can be used in various forms like black ginger. It can be a processed product such as powder, squeezed juice, or extract. The processed product of specific ingredients can be produced with reference to the description of the processed product of black ginger in this specification.

The specific component may be produced by a method commonly known by those skilled in the art, or may be commercially available.

Each of the specific components alone hardly exhibits a UCP1 expression-promoting effect or brown adipocyte differentiation-promoting effect. Surprisingly, however, it exhibits at least one of these effects when combined with black ginger. Therefore, it can be said that the UCP1 expression promoting action and brown adipocyte differentiation promoting action by the combination of black ginger and the specific component are synergistic rather than additive actions.

The term "expression promoting action" as used herein means, for example, in the case of UCP1 expression promoting action, promoting the expression level of the UCP1 gene in a subject, increasing the translation amount of the UCP1 protein, and activating UCP1. At least any one action among In addition, brown adipocyte activation action refers to at least one action of activating brown adipocytes and increasing the number of brown adipocytes.

Regarding the UCP1 expression promoting action, as described in Non-Patent Document 1, the function of UCP1 is reduced in obese animals, UCP1 is increased in animals that do not become obese even if they eat a lot, and UCP1 is artificially increased. It has been known that mice with reduced expression of the protein are obese and those with high expression are lean. Therefore, an anti-obesity effect can be expected due to the action of promoting UCP1 expression, and a substance that actually has an action of promoting UPC1 expression promotes lipolysis in white adipocytes and at the same time activates UCP1 to convert free fatty acids into heat. , can eventually reduce body fat.

The heat production promoting action refers to, for example, the action of promoting heat production from neutral lipids by brown adipocytes. A neutral lipid-lowering action refers to, for example, an action of degrading neutral lipids to lower the total amount of neutral lipids in the body. The sebum-suppressing action refers to, for example, the action of suppressing the generation of sebum. The action of promoting fat metabolism refers to, for example, the action of qualitatively converting adipocytes and adipose tissue that form an obese state into small normal adipocytes. The body fat reducing action refers to, for example, the action of reducing body fat by converting free fatty acids into heat. Metabolism-promoting action and anti-obesity action refer to, for example, the action of promoting metabolism to reduce body fat and the action of suppressing obesity due to such action. The energy production promoting action refers to, for example, the action of producing energy through heat production from neutral lipids by brown adipocytes. Each action in this paragraph includes the action of the meaning described, but also includes actions realized by other mechanisms of action.

The anti-disease effect exhibited by the anti-disease composition such as the anti-obesity composition of the present invention is, for example, in the case of the anti-obesity effect exhibited by the anti-obesity composition, current or future obesity or obesity in the subject. It refers to suppressing or delaying becoming a condition or improving the condition. In addition, insulin resistance refers to a state in which the main action of insulin, namely the action of promoting absorption of sugar, is weakened in the liver, fat cells, skeletal muscle, and the like. The anti-insulin resistance effect refers to suppressing or delaying worsening of the current or future insulin resistance index value in a subject by the SSPG (Steady-state plasma glucose) method or the like, or improving the value. Say.

Obesity is known to cause various diseases, such as type 2 diabetes, hypertension, and hyperlipidemia. Furthermore, these diseases may lead to stroke, ischemic heart disease, and the like. In the obese state, hypertrophy of adipocytes is observed, and TNF-α and free fatty acids (FFA) are secreted, which inhibit sugar uptake in insulin target cells such as muscle cells and liver cells, and insulin The secretion of adiponectin, which promotes the action of , is suppressed, causing a decrease in insulin sensitivity at the cellular level, resulting in insulin resistance. The obesity-induced diseases described above are viewed as a series of dysmetabolic conditions based on insulin resistance. Therefore, by using the composition of the present invention, it is possible to prevent or improve obesity and diseases associated with obesity such as type 2 diabetes, hypertension and hyperlipidemia.

Here, the prevention and improvement of type 2 diabetes refers to suppressing or delaying the development of a diabetic state or borderline state, or bringing these states closer to a state called normal range. Prevention and amelioration of hypertension refers to suppressing or delaying hypertension or borderline hypertension, or bringing the state closer to the normal range. The prevention and amelioration of hyperlipidemia refers to suppressing or delaying hyperlipidemia or a borderline state, or bringing the state closer to a normal state.

The method for producing the composition of the present invention is not particularly limited, and for example, a solid composition can be obtained by mixing black ginger and specific components at room temperature or under heating. Alternatively, the solid composition can be dissolved in a solvent such as water to form a liquid composition. Furthermore, a liquid composition can be obtained by adding and mixing other solid components to black ginger or a liquid of specific components. The obtained liquid composition may be pulverized through a drying treatment. Examples of the drying treatment method in this case include, but are not limited to, spray drying, freeze drying, and the like.

In the present invention, the contents of the black ginger extract and the specific component are not particularly limited, for example, their mass ratio ([black ginger]:[total amount of specific component]) is 1: 0.001 to 20, It is preferably 1:0.01-10, more preferably 1:0.05-5.

The composition of the present invention can be used as it is or mixed with other ingredients depending on the application. Thus, the composition of the present invention can contain various ingredients in addition to black ginger and specific ingredients as long as the objects of the present invention can be achieved.

For example, the compositions of the present invention may further contain additives used in normal processing such as excipients, fillers, binders, thickeners, emulsifiers, colorants, fragrances, perfume oils and the like. . The amount of the additive used is not particularly limited as long as it does not interfere with the solution of the problems of the present invention, and is adjusted as appropriate.

The composition of the present invention is not particularly limited as long as it is in a commonly used form, and examples thereof include liquid, lotion, mousse, gel, emulsion, suspension, cream, ointment, sheet, and aerosol. , spray, stick, powder, granules, tablets, rods, plates, blocks, solids, pastes, capsules, caplets, and the like.

The composition of the invention can be used as a parenteral composition, eg in a form suitable for cosmetics. That is, one aspect of the composition of the present invention is a cosmetic composition. For example, the composition of the present invention can be processed into various forms such as lotions, emulsions, gels, creams, ointments, etc. as it is or mixed with additives that are commonly used in the processing of cosmetics. . Specifically, it can be used as lotion, cosmetic cream, milky lotion, cream, pack, hair tonic, hair cream, shampoo, hair rinse, treatment, facial cleanser, foundation, hair restorer, water-based ointment, spray, and the like.

The content of black ginger contained in the composition of the present invention is not particularly limited as long as the UCP1 expression promoting action and / or brown adipocyte differentiation promoting action is observed, but as an oral composition, for example, It is 0.0001 wt% or more, preferably 0.001 wt% or more, and for parenteral compositions such as cosmetics, it is, for example, 0.00001 wt% or more, preferably 0.0001 wt% or more.

When the composition of the present invention is an oral composition, it includes a composition having a taste-improving effect by containing black ginger and a specific component.

A specific embodiment of the composition of the present invention includes, for example, a composition containing 40 to 90% by weight of black ginger and 10 to 60% by weight of any one of the specific ingredients. Among them, a composition containing 50 to 80 wt % of black ginger and 20 to 50 wt % of any one of the specific ingredients is more preferable.

Another specific embodiment of the composition of the present invention includes a composition containing 40 to 90 wt% of black ginger and any two of the specific ingredients in a total ratio of 10 to 60 wt%. Among them, a composition containing 50 to 80 wt% of black ginger, 10 to 30 wt% of one of the two components, and 10 to 20 wt% of the other component can be mentioned.

Another specific embodiment of the composition of the present invention includes a composition containing 40 to 90 wt% of black ginger and any three of the specific ingredients in a total ratio of 10 to 60 wt%. Among these, 50 to 80 wt% of black ginger, 7.5 to 20 wt% of the first component among the three components, 7.5 to 20 wt% of the second component, and 5 to 10 wt% of the third component. %.

A specific aspect of the composition of the present invention described above indicates the ratio of black ginger and specific components to the total mass. That is, the ratio of the black ginger and the specific component above indicates the ratio of each of the black ginger and the specific component to the total mass of the black ginger and the specific component, excluding additives.

Hereinafter, formulation examples according to specific aspects of the composition of the present invention will be shown, but the present invention is not limited to these formulation examples, and various aspects of the present invention can be used as long as the problems of the present invention can be solved. can take

(Formulation example 1: Lotion)
The total is 100 parts by mass, black ginger extract 0.01 parts by mass, ginger extract 0.01 parts by mass, Ketsumeishi 0.01 parts by mass, glycerin 10 parts by mass, diglycerin 3 parts by mass, 1,3-butylene glycol 12 parts by weight, pentylene glycol 3 parts by weight, sodium hyaluronate 0.1 parts by weight, citric acid 0.01 parts by weight, sodium citrate 0.02 parts by weight, xanthan gum 0.1 parts by weight, methylparaben 0.15 parts by weight , 0.2 parts by mass of carbomer, 0.03 parts by mass of sodium hydroxide and the remainder of water were mixed to prepare the composition of the present invention in the form of a lotion.

(Formulation Example 2: Shampoo)
The total is 100 parts by weight, black ginger extract 0.01 parts by weight, hop extract 0.02 parts by weight, caffeine 0.01 parts by weight, sodium laureth sulfate 7.5 parts by weight, cocamidopropyl betaine 4.2 parts by weight parts by mass, cocamide DEA 3 parts by mass, 1,3-butylene glycol 0.1 parts by mass, polyquaternium-10 0.225 parts by mass, citric acid 0.15 parts by mass, sodium citrate 0.05 parts by mass, phenoxyethanol 0. A composition of the invention was prepared in the form of a shampoo by mixing 9 parts by weight and the remainder of the water.

(Formulation Example 3: Soap)
The total is 100 parts by weight, 0.5 parts by weight of black ginger pulverized, 0.2 parts by weight of melilot extract, 0.1 parts by weight of elastin, 2 parts by weight of glycerin, 1 part by weight of olive oil, 0.1 parts by weight of sodium EDTA-4 A composition of the invention was prepared in the form of a soap by mixing and solidifying parts by weight tetrasodium etidronate 0.2 parts by weight and the balance soap base.

(Formulation Example 4: Emulsion)
The total is 100 parts by mass, black ginger extract 0.1 parts by mass, alanine 0.1 parts by mass, arginine 0.1 parts by mass, sucrose fatty acid ester 3 parts by mass, glycerin 12 parts by mass, squalane 6 parts by mass, dimethyl 24 parts by mass of silicone oil, 1 part by mass of polypropylene glycol, 0.06 parts by mass of thickener, 0.2 parts by mass of phenoxyethanol, 5 parts by mass of ethanol, 0.01 parts by mass of sodium hydroxide and the rest of purified water, A composition of the invention was prepared in the form of an emulsion.

(Composition example 5: cosmetic cream)
Taking the total as 100 parts by mass, 0.1 parts by mass of black ginger extract, 0.1 parts by mass of isomaltooligosaccharide, 0.1 part by mass of fructo-oligosaccharide, 15.0 parts by mass of squalane, and 4.0 parts by mass of octyldodecyl myristate , Hydrogenated soybean phospholipid 0.2 parts by mass, butyl alcohol 2.4 parts by mass, hydrogenated oil 1.5 parts by mass, stearic acid 1.5 parts by mass, lipophilic monostearate glycerol 1.5 parts by mass, mono Polyglyceryl stearate 0.5 parts by weight, behenyl alcohol 0.8 parts by weight, polyglyceryl monomyristate 0.7 parts by weight, white beeswax 0.3 parts by weight, d-δ-tocopherol 0.1 parts by weight, methylparaben 0.3 parts by weight parts, C10-30 alkyl-modified carboxyvinyl polymer 0.2 parts by mass, carboxyvinyl polymer 0.1 parts by mass, 1,3-butanediol 18.0 parts by mass, sodium hydroxide 0.1 parts by mass and the rest of purified water By mixing, the composition of the invention was prepared in the form of a cosmetic cream.

(Formulation Example 6: pack agent)
The total is 100 parts by mass, 0.1 part by mass of black ginger extract, 0.01 part by mass of gallic acid, 20.0 parts by mass of polyvinyl alcohol, 5.0 parts by mass of glycerin, 20.0 parts by mass of ethanol, and kaolin. 0 parts by mass, 0.2 parts by mass of preservative, 0.1 part by mass of perfume and the rest of purified water were mixed to prepare the composition of the present invention in the form of a pack agent.

(Formulation Example 7: Tablet)
The total is 100 parts by weight, black ginger powder 10 parts by weight, ginger extract 8 parts by weight, caffeine 5 parts by weight, melilot 5 parts by weight, crystalline cellulose 20 parts by weight, lactose 50 parts by weight, magnesium stearate 4 parts by weight and cornstarch The composition of the invention was prepared in tablet form by mixing and compressing the remainder.

(Formulation Example 8: Tablet)
The total is 100 parts by mass, 10 parts by mass of black ginger powder, 8 parts by mass of ketsumeishi powder, 5 parts by mass of melilot, 0.5 parts by mass of isomaltooligosaccharide, 0.5 parts by mass of fructo-oligosaccharide, 20 parts by mass of crystalline cellulose, lactose A composition of the invention was prepared in tablet form by mixing and tableting 50 parts by weight magnesium stearate 4 parts by weight and the rest cornstarch.

(Formulation Example 9: Granules)
The total is 100 parts by mass, 10 parts by mass of black ginger powder, 15 parts by mass of hop powder, 5 parts by mass of Ketsumeishi extract, 10 parts by mass of lactose, 1 part by mass of calcium stearate and the rest of crystalline cellulose by mixing and granulating , the composition of the present invention was prepared in the form of granules.

(Formulation Example 10: Capsules)
The total amount is 100 parts by mass, and 10 parts by mass of black ginger extract, 20 parts by mass of ginger extract, 5 parts by mass of elastin, 8 parts by mass of lecithin and the rest of olive oil are mixed to prepare the content liquid, which is used as the capsule shell. The compositions of the present invention were prepared in the form of capsules by encapsulating in

(Formulation Example 11: Liquid)
The total is 100 parts by mass, black ginger extract powder 0.84 parts by mass, arginine 1 part by mass, alanine 1 part by mass, fructose glucose liquid sugar 10 parts by mass, citric acid 1 part by mass, sodium benzoate 0.02 parts by mass, 2 parts by mass of a fragrance formulation, 0.05 parts by mass of sucralose, 0.03 parts by mass of acesulfame potassium, and the rest of purified water were mixed to prepare the composition of the present invention in the form of a liquid formulation.

[1. Influence evaluation of UCP1 expression level by combination of black ginger extract and auxiliary material]
(1) Production of pulverized black ginger After washing the black ginger rhizome, it was sliced into pieces of about 1 to 10 mm and dried in the sun for one day. After that, it was dried for 4 to 6 hours in an oven dryer set at 40 to 100° C., coarsely pulverized, and then sterilized at 130 to 200° C. for 5 to 20 seconds. The sterilized coarsely pulverized product was pulverized by a pulverizer to obtain pulverized black ginger rhizome. In the same manner, pulverized stems, pulverized leaves and pulverized flowers of black ginger were obtained. These were used as ground black ginger.

(2) Production of black ginger extract 300 g of ground black ginger obtained by the method described above was weighed and placed in an Erlenmeyer flask together with 3 L of 60 vol% ethanol. The first extraction was performed by standing at room temperature for 24 hours while stirring several times during the process. This was filtered under reduced pressure to obtain a first extract. The residue after filtration under reduced pressure was immersed in 3 L of 60 vol% ethanol and allowed to stand at room temperature for 24 hours for the second extraction. This was filtered under reduced pressure to obtain a second extract. An extraction mixture obtained by combining the first and second extracts was concentrated under reduced pressure to obtain a black ginger extract. The resulting black ginger extract had a 57DMF content of 9.27 wt%.

(3) Test Substances Hops, Ketsumeishi, Melilot extract, ginger, elastin, gallic acid, caffeine, arginine, alanine, isomalto-oligosaccharides, fructo-oligosaccharides, glutamic acid and methionine were used as test substances.

(4) Preparation of collagenase solution A DMEM medium prepared to contain 0.2% (W/V) collagenase and 1% (W/V) BSA was shaken at room temperature for 1 hour to prepare a collagenase solution. prepared.

(5) Preparation of Brown Adipocyte Fluid ICR mice (Kyudou) were euthanized with diethyl ether, and brown adipose tissue was excised from the back. From the obtained brown adipose tissue, tweezers were used to remove adipose tissue, blood vessels, muscle, etc. adhering to the periphery of the brown adipose tissue, and then the brown adipose tissue was washed three times in DMEM. The brown fat was then immersed in a collagenase solution and subjected to a mincing treatment in which the brown fat was finely minced with scissors in the solution. Cell suspensions were obtained by incubating the minced brown fat in collagenase solution for 1 hour at 37°C. The resulting cell suspension was filtered through a cell strainer with a pore size of 100 μm, and then centrifuged (800 rpm, 5 min, 20° C.). The precipitated cells were then suspended in DMEM to obtain a cell suspension. The resulting cell suspension was then filtered using an autoclaved sterilized 25 μm filter. After centrifuging the filtered supernatant (800 rpm, 5 min, 20° C.), the precipitated cells were suspended in DMEM containing 10 vol% FBS to obtain a brown adipocyte solution.

(6) Preparation of medium DMEM containing 10 vol% FBS was used as a growth medium.

A differentiation induction medium was prepared containing 2.5 μM dexamethasone, 10 μg/ml insulin and 0.5 mM IBMX in growth medium.

As a maintenance medium, a growth medium containing 10 μg/ml insulin was prepared using the above insulin solution.

A test substance-containing medium was prepared as follows. Specifically, each test substance was dissolved in DMSO, diluted with a maintenance medium to a DMSO final concentration of 0.5 vol%, and filtered. After sterilization, predetermined concentrations using a maintenance medium containing 0.5 vol% DMSO, namely, black ginger extract, hops (cones), ketsumeishi, melilot extract, ginger, elastin, gallic acid, caffeine, arginine, alanine, iso Maltooligosaccharides, fructo-oligosaccharides, glutamic acid and methionine were diluted to 20 μg/ml or 40 μg/ml, and troglitazone was diluted to 10 μM.

(7) Place 5 ml of the collagen coating solution in a cell culture 75 cm ² flask, allow to stand at room temperature for about 1 hour, remove the collagen coating solution by aspiration, and wash twice with 5 ml of PBS to obtain a collagen-coated flask. rice field.

The brown adipocyte solution was added to the collagen-coated flask, and the brown adipocytes were cultured for 24 hours in a 37° C., 5% CO ₂ incubator. Then, the cultured brown adipocytes were washed once with a growth medium, replaced with a new growth medium, and cultured until subconfluent.

The cultured brown adipocytes were subjected to trypsinization and allowed to float. The obtained floating cells were seeded in each well of a 24-well plate coated with collagen (350 μL/well of collagen coating solution, 350 μL/well of PBS washing×2 times).

Brown adipocytes were cultured until confluent with growth medium. After removing the medium from each well, 500 μl of a differentiation-inducing medium was added to each well and cultured for 48 hours.

After removing the differentiation-inducing medium, 500 μl of 20 μg/ml test substance-containing medium was added and cultured for 6 days. Medium was changed every other day. For the medium in which the black ginger extract and each test substance were combined, 250 µl of each 40 µg/ml test substance-containing medium was added so that the final concentration of each test substance was 20 µg/mL.

After 8 days of culture, the supernatant was recovered, RNA was recovered using RNeasy Mini Kit (Qiagen), and cDNA was synthesized using QuantiTect Reverse Transcription Kit (Qiagen).

Using the resulting cDNA as a template, quantitative real-time PCR was performed using primers for the UCP1 gene (Qiagen) and a Rotor-Gene SYBR Green PCR Kit (Qiagen) to measure the UCP1 mRNA expression level. As an endogenous control, GAPDH mRNA expression level was measured using GAPDH primers (Qiagen).

(8) For each of the test substances evaluated hops, ketsumeishi, melilot extract, ginger, elastin, gallic acid, caffeine, arginine, alanine, isomalto-oligosaccharides, fructo-oligosaccharides, glutamic acid and methionine, black ginger extract alone, test Table 1 shows the measurement results of the UCP1 mRNA expression level (relative expression level to the endogenous control) when the substance alone and the combination of the black ginger extract and the test substance were provided.

As shown in Table 1, when the test substances are hops, ketsumeishi, melilot extract, ginger, elastin, gallic acid, caffeine, arginine, alanine, isomalto-oligosaccharides and fructo-oligosaccharides, black ginger extract alone or test substance The UCP1 expression level was higher when the black ginger extract and the test substance were combined than when they were used alone.

On the other hand, surprisingly, when glutamic acid and methionine were used as test substances, the UCP1 expression level decreased when the black ginger extract was combined with the test substance, compared to the black ginger extract alone or the test substance alone. rice field.

More surprisingly, when hops, ketsumeishi, melilot extract, elastin, gallic acid, caffeine, arginine and isomalto-oligosaccharides were used as test substances, the total UCP1 expression level was higher than that of the black ginger extract alone and the test substance alone. , the UCP1 expression level of the combination of the black ginger extract and the test substance was large.

These results indicate that black ginger extract is synergistic rather than additive when combined with hops, ketsumeishi, melilot extract, ginger, elastin, gallic acid, caffeine, arginine, alanine, isomalto-oligosaccharides or fructo-oligosaccharides. It was found that the mRNA expression level of UCP1 was specifically promoted.

[2. Influence evaluation of sensory test by combination of black ginger extract and auxiliary material]
Isomalto-oligosaccharides, fructo-oligosaccharides, milk oligosaccharides, alanine, and serine were used as test substances, and black ginger extract alone, test substances alone, and compositions combining black ginger extracts and test substances were used as test substances. , Sweetness, bitterness, acridness, etc. were evaluated sensory. 2 g of the test material was suspended in 100 ml of water to obtain each test sample. Nine healthy adults were randomly selected as subjects.

Each of these 9 subjects was orally ingested each test sample, and sensory evaluation was performed by a scoring method. The evaluation items were 7 items of "aroma", "taste preference", "ease of drinking", "sweetness preference", "bitterness", "aftertaste" and "palatability".

Each item of the sensory evaluation was scored as follows. The rating for each item for the black ginger extract alone was set at 5.
Aroma: Bad 1 ← 5 → 9 Preference for good taste: Unfavorable taste 1 ← 5 → 9 Favorable taste Ease of drinking: Bad 1 ← 5 → 9 Preference for good sweetness: Not sweet 1 ← 5 → 9 Bitter sweet Sa: Bitter 1 ← 5 → 9 No bitter aftertaste: Bad 1 ← 5 → 9 Good palatability: Low palatability 1 ← 5 → 9 High palatability

The results of the sensory evaluation, in which the scores for each item were averaged, are shown in FIGS. 1 to 5 for each test substance.

As shown in FIGS. 1 to 5, the composition combining the black ginger extract and the test substance was generally superior to the black ginger extract alone or the test substance alone in the endpoints. Based on these results, when the test substances are isomalto-oligosaccharides, fructo-oligosaccharides, milk oligosaccharides, alanine, and serine, the composition containing the black ginger extract and the test substance has excellent palatability in eating and drinking. rice field.

The composition of the present invention contains black ginger and specific ingredients that can be applied parenterally or orally, and is particularly useful for subjects suffering from cellulite, obesity, and diseases associated therewith. and is conducive to the health and welfare of such subjects.

Claims (2)

An anti-obesity oral composition containing black ginger (Kaempferia parviflora) and caffeine. An oral composition for reducing body fat, containing black ginger (Kaempferia parviflora) and caffeine.

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