JP2011001311A5 - - Google Patents

Description

（１）
[式中、Ｒ ₁ 及びＲ ₂ は、それぞれ独立に、水素原子、炭素数１〜４のアルキル基を表し、Ｒ ₃ は、水素原子、炭素数１〜４の直鎖又は分岐のアルキル鎖を有するアルコキシ基、水素原子又は炭素原子が複素原子で置換されていてもよい直鎖又は分岐のアルキル又はアルケニル基を表し、Ｒ ₄ は、水素原子、水酸基、炭素数１〜４のアルキル鎖を有するアルコキシ基、エ−テル結合により結合した五炭糖又は六炭糖を表し、Ｒ ₅ は、水素原子、又は、水素原子又は炭素原子が複素原子に置換されていてもよい直鎖、分岐又は環状のアルキル基を表す。ただし、Ｒ ₃ 及びＲ ₅ は、互いに結合して環状構造をとってもよい。ｎは、０又は１の整数を表す。]

(1)
[Wherein, R ₁ and R ₂ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₃ represents a hydrogen atom or a linear or branched alkyl chain having 1 to 4 carbon atoms. Represents a linear or branched alkyl or alkenyl group in which an alkoxy group, a hydrogen atom or a carbon atom may be substituted with a hetero atom, and R ₄ has a hydrogen atom, a hydroxyl group, or an alkyl chain having 1 to 4 carbon atoms. Represents an pentose or hexose linked by an alkoxy group or an ether bond, and R ₅ represents a hydrogen atom or a straight, branched or cyclic group in which a hydrogen atom or a carbon atom may be substituted with a hetero atom. Represents an alkyl group. However, R ₃ and R ₅ may be bonded to each other to form a cyclic structure. n represents an integer of 0 or 1. ]

The Japanese diet is rapidly changing to a diet rich in Western-type animal proteins and fats, and further, due to lifestyle changes such as lack of exercise due to the automobile society, obesity is rapidly increasing. Obesity is known to be one of the risk factors for adult diseases such as hypertension, arteriosclerosis, and diabetes, and also has a great impact on diseases such as fatty liver, low back pain, and knee osteoarthritis. At present, managing risk factors for adult diseases such as obesity and promoting health are not only to maintain personal health, but also to reduce public burdens such as health insurance costs. Is recognized as a major social issue. In addition, obesity is often caught as a cosmetic problem regardless of gender, and therefore, attention is being paid to various diet methods such as diet restriction, exercise, and health food for the purpose of eliminating obesity.

U CP1 resides in the mitochondria of brown adipose cells, a special membrane proteins to maintain the body temperature 32 kilodaltons. The ATP synthesis of the electron transport system in mitochondria is closely coupled by a proton concentration gradient in the inner membrane. Since the uncoupled protein eliminates the proton concentration gradient in a short-circuited manner, when it is activated, the chemical energy of the oxidized substrate is not used for ATP synthesis but is converted to heat. The heat generated therefrom is used to maintain body temperature and dissipate surplus energy, and is thus related to energy consumption. Furthermore, in UCP1 knockout mice, it has been confirmed that obesity is not caused by intake of not only a normal diet but also a high fat diet (see, for example, Non-Patent Document 1). For this reason, with the expectation of reducing the risk of adult diseases, research on obesity improvement focusing on heat-producing proteins has been actively conducted. However, there are no known chemical structural properties or structure-activity relationships related to the promotion of activation of heat-producing proteins, activation, or structure-activity relationships. It can be said that it is an urgent issue to suppress obesity.

It is known that cyanidin derivatives known as pigments contained in black bean skin and the like and glycosides thereof have various biological activities. Examples of the biological activity of the cyanidin derivative and its glycoside include an antioxidant action (for example, see Non-Patent Document 2), a blood flow improving action (for example, see Patent Document 1), and a melanin production inhibitory action (for example, a patent). Reference 2), obesity prevention and improvement action (for example, see Patent Document 3), antiviral activity (for example, see Patent Document 4), matrix metalloproteinase inhibitory action (for example, see Patent Document 5) Insulin secretion promoting action (see, for example, Patent Document 6), late glycation end product formation inhibitory action (see, for example, Patent Document 7), and the like are known.

Also, the quinic acid, a series of compounds having a chemical structure such as caffeic acid is bound are called chlorogenic acids, it is typical to chlorogenic acid (5-caffeoylquinic acid). Chlorogenic acids classified as polyphenols are abundant in raw coffee beans and are known as one of the components that form a unique aroma. Chlorogenic acids have various biological activities, antioxidative action (see, for example, Non-Patent Document 2), pigment fading prevention action (see, for example, Patent Document 8), blood glucose level increase inhibiting action, and lipid metabolism improving method (See, for example, Patent Document 9), sensory stimulation enhancing action (for example, see Patent Document 10), angiogenesis inhibitory action (for example, see Patent Document 11), pungency enhancing action (for example, see Patent Document 12) Etc. have been reported.

The fat cells, two types of white adipocytes and brown fat cells are present. White adipocytes are cells that serve to accumulate energy as neutral fat in the cells, whereas brown adipocytes take in free fatty acids in the blood to produce and radiate heat to generate energy. It is a cell that plays a role in radiating water. The cyanidin derivatives and chlorogenic acids described above have an anti-obesity and ameliorating action, and a lipid metabolism-improving action. : PPAR) has been reported to control the expression of various genes having a PPAR gene responsive element and to participate in physiological and pathological phenomena. However, cyanidin derivatives and chlorogenic acids are present in the mitochondria of brown adipocytes, take up free fatty acids in the blood, take part in the release of energy by producing and radiating heat, in particular, It is not known at all to act on UCP1 . In obese people, it has been reported that heat production in brown adipocytes is not sufficient and it is difficult to consume energy. Therefore, a substance having an action of promoting the expression of heat production protein is suitable for dieting. Conceivable.

（１）
[式中、Ｒ ₁ 及びＲ ₂ は、それぞれ独立に、水素原子、炭素数１〜４のアルキル基を表し、Ｒ ₃ は、水素原子、炭素数１〜４の直鎖又は分岐のアルキル鎖を有するアルコキシ基、水素原子又は炭素原子が複素原子で置換されていてもよい直鎖又は分岐のアルキル又はアルケニル基を表し、Ｒ ₄ は、水素原子、水酸基、炭素数１〜４のアルキル鎖を有するアルコキシ基、エ−テル結合により結合した五炭糖又は六炭糖を表し、Ｒ ₅ は、水素原子、又は、水素原子又は炭素原子が複素原子に置換されていてもよい直鎖、分岐又は環状のアルキル基を表す。ただし、Ｒ ₃ 及びＲ ₅ は、互いに結合して環状構造をとってもよい。ｎは、０又は１の整数を表す。]

(1)
[Wherein, R ₁ and R ₂ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₃ represents a hydrogen atom or a linear or branched alkyl chain having 1 to 4 carbon atoms. Represents a linear or branched alkyl or alkenyl group in which an alkoxy group, a hydrogen atom or a carbon atom may be substituted with a hetero atom, and R ₄ has a hydrogen atom, a hydroxyl group, or an alkyl chain having 1 to 4 carbon atoms. Represents an pentose or hexose linked by an alkoxy group or an ether bond, and R ₅ represents a hydrogen atom or a straight, branched or cyclic group in which a hydrogen atom or a carbon atom may be substituted with a hetero atom. Represents an alkyl group. However, R ₃ and R ₅ may be bonded to each other to form a cyclic structure. n represents an integer of 0 or 1. ]

（２）
[式中、Ｒ ₆ 、Ｒ ₇ 、Ｒ ₉ 及びＲ ₁₀ は、それぞれ独立に、水素原子、炭素数１〜４のアルキル基を表し、Ｒ ₈ は、水酸基、炭素数１〜４のアルキル鎖を有するアルコキシ基、エ−テル結合により結合した五炭糖又は六炭糖を表し、X ^- は陰イオンを表す。]

(2)
[Wherein R ₆ , R ₇ , R ₉ and R ₁₀ each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₈ represents a hydroxyl group or an alkyl chain having 1 to 4 carbon atoms. Represents an alkoxy group having a pentose or hexose linked by an ether bond, and X ⁻ represents an anion. ]

<3> The compound represented by the general formula (2) is a compound represented by the following general formula (3), a free base thereof, an isomer thereof and / or a pharmacologically acceptable salt thereof. The heat-producing protein expression promoter according to < 2> , which is characterized in that it exists.

（３）
[式中、Ｒ ₁₁ 、Ｒ ₁₂ 、Ｒ ₁₃ 及びＲ ₁₄ は、それぞれ独立に、水素原子、炭素数１〜４のアルキル基を表し、Ｘ ^- は、陰イオンを表す。]

(3)
[Wherein, R ₁₁ , R ₁₂ , R ₁₃ and R ₁₄ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and X ⁻ represents an anion. ]

<4> The compound represented by the general formula (2) is a compound represented by the following general formula (4), a free base thereof, an isomer thereof and / or a pharmacologically acceptable salt thereof. The heat-producing protein expression promoter according to < 2> , which is characterized in that it exists.

（４）
[式中、Ｒ ₁₅ 、Ｒ ₁₆ 、Ｒ ₁₈ 及びＲ ₁₉ は、それぞれ独立に、水素原子、炭素数１〜４のアルキル基を表し、Ｒ ₁₇ は、エ−テル結合により結合した五炭糖又は六炭糖を表し、X ^- は陰イオンを表す。]

(4)
[Wherein, R ₁₅ , R ₁₆ , R ₁₈ and R ₁₉ each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₁₇ represents a pentose linked by an ether bond or Represents a hexose sugar, and X ⁻ represents an anion. ]

（５）
[式中、Ｒ ₂₀ 及びＲ ₂₁ は、それぞれ独立に水素原子、炭素数１〜４のアルキル基を表し、Ｒ ₂₂ は、水酸基、炭素数１〜４のアルキル鎖を有するアルコキシ基、エ−テル結合により結合したキナ酸を表す。]

(5)
[Wherein, R ₂₀ and R ₂₁ each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₂₂ represents a hydroxyl group, an alkoxy group having an alkyl chain having 1 to 4 carbon atoms, or ether. It represents quinic acid bound by a bond. ]

<7> The heat produced protein expression promoter, cyanidin (cyanidin), Ideain (Ideain), cyanidin 3- arabinoside (Cyanidin 3-arabinoside), delphinidin (Delphinidine), quercetin 3- galactoside (Quercetin 3-galactoside), chlorogenic The thermogenic protein expression promoter according to any one of <1> to <6> , which is a chlorogenic acid and / or a pharmacologically acceptable salt thereof.
<8> The heat-producing protein according to any one of <1> to <7>, wherein the heat-producing protein expression promoter is an uncoupling protein 1: abbreviated UCP1 expression promoter. Expression promoter.
<9><1> - is one or selected from the heat-producing protein expression promoter of any crab description of <8>, characterized in that it contains two or more kinds, composition for slimming.
<10> The composition for slimming according to <9>, wherein the heat-producing protein expression promoter is contained as an essence of a plant belonging to the genus Aroniaceae.
<11> The composition for slimming according to < 10>, wherein the plant belonging to the genus Aronia belonging to the family Rosaceae is an Aronia genus Aronia.
<12> The slimming product according to any one of <9> to <11>, wherein the thermogenic protein expression promoter is contained in an amount of 0.001% by mass to 20% by mass with respect to the total amount of the composition. Composition.
<13> The slimming composition according to any one of <9> to <12>, which is an orally administered composition.
<14> The slimming composition according to any one of <9> to <13>, which is a food, a pharmaceutical product, or a cosmetic.
<15> A method for producing a slimming composition containing a heat-producing protein expression promoter , wherein a plant belonging to the genus Aroniaceae is selected, a fruit part is collected, and extracted with a polar solvent, A production method, characterized in that a fraction containing a flavonoid and an aglycon thereof is obtained by purification, a heat-producing protein expression promoting action in the fraction is confirmed, and then blended into the composition.

Here, to describe the compound represented by the general formula (1), in the general formula (1), R ₁ and R ₂ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. , R ₃ is a hydrogen atom, an alkoxy group having a linear or branched alkyl chain having 1 to 4 carbon atoms, a linear or branched alkyl or alkenyl group in which the hydrogen atom or carbon atom may be substituted with a hetero atom R ₄ represents a hydrogen atom, a hydroxyl group, an alkoxy group having an alkyl chain having 1 to 4 carbon atoms, a pentose or hexose linked by an ether bond, and R ₅ represents a hydrogen atom, or Represents a linear, branched or cyclic alkyl group in which a hydrogen atom or a carbon atom may be substituted with a hetero atom. However, R ₃ and R ₅ may be bonded to each other to form a cyclic structure. n represents an integer of 0 or 1. R ₁ and R ₂ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Specific examples include a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, n -Butyl, isobutyl group, sec-butyl group and tert-butyl group can be preferably exemplified, and hydrogen atom and methyl group are particularly preferable. R ₃ represents a hydrogen atom, an alkoxy group having a linear or branched alkyl chain having 1 to 4 carbon atoms, a linear or branched alkyl or alkenyl group in which the hydrogen atom or carbon atom may be substituted with a hetero atom. Represents. However, R ₃ and R ₅ may be bonded to each other to form a cyclic structure. Specific examples of R ₃ are preferably a hydrogen atom, a methoxy group, an ethoxy group, a propyloxy group, a butyloxy group, and the like. Examples of the group in which R ₃ and R ₅ are bonded to each other to form a cyclic structure include 3-hydroxyflavylium group, 3,5-dihydroxyflavylium group, 3,7-dihydroxyflavylium group, 3,5,7-tri Preferred examples include hydroxyflavylium group, 3,5,7-trihydroxy-4H-chromen-4-one group and the like. Among these, a hydrogen atom, a 3,5,7-trihydroxyflavylium group, and a 3,5,7-trihydroxy-4H-chromen-4-one group can be preferably exemplified. R ₄ represents a hydrogen atom, a hydroxyl group, an alkoxy group having an alkyl chain having 1 to 4 carbon atoms, or a pentose or hexose linked by an ether bond. , Methoxy group, ethoxy group, propyloxy group, butyloxy group, and the like, and pentoses bonded by an ether bond include ribose, lyxose, xylos, arabinose, and apio. As the hexoses to which sesame and the like are bonded by an ether bond, allose, tarose, gloss, artrose, mannose, galactose, idose, etc. are preferable. Among them, a hydroxyl group, a group in which arabinose is bonded by an ether bond (arabinose residue), a group in which galactose is bonded by an ether bond (galactose residue), etc. It can illustrate suitably. The position at which the pentose or hexose is bonded to the ether is not particularly limited. In particular, in the case of pentose, the position at the 4-position of the sugar chain, and in the case of hexose. It is preferable that an ether bond is formed at the 5-position of the sugar chain. R ₅ represents a hydrogen atom or a linear, branched or cyclic alkyl group in which a hydrogen atom or a carbon atom may be substituted with a hetero atom. However, R ₃ and R ₅ may be bonded to each other to form a cyclic structure. Specific examples of R ₅ include hydrogen atom, acetyl group, propionyl group, butyryl group, isobutyryl group, valeryl group, hexanoyl group, methoxycarbonyl group, ethoxycarbonyl group, propyloxycarbonyl group, benzyl group, benzoyl group, Preferred examples include groups in which quinic acid is ester-bonded. The position where the quinic acid is ester-bonded is not particularly limited, but the 5-position is particularly preferable. Examples of the group in which R ₃ and R ₅ are bonded to form a cyclic structure include 3-hydroxybenzopyrylium group, 3,5-dihydroxybenzopyrylium group, 3,7-dihydroxybenzopyrylium group, 3,5, Preferred examples include a 7-trihydrobenzobenzopyrylium group and a 3,5,7-trihydroxy-4H-chromen-4-one group. Among these, a hydrogen atom, a hydroxyl group, a 3,5,7-trihydroxybenzopyrylium group, a 3,5,7-trihydroxy-4H-chromen-4-one group, and a group in which quinic acid is ester-bonded Etc. can be suitably exemplified. N represents an integer of 0 or 1. Preferred examples of the compound represented by the general formula (1) include a compound represented by the general formula (2) or a compound represented by the general formula (5). Furthermore, among the compounds represented by the general formula (2), more preferable examples include compounds represented by the general formula (3) or the general formula (4). The compound represented by the general formula (1), isomers thereof and / or pharmacologically acceptable salts thereof are excellent in heat-producing protein expression promoting action, in particular, uncoupling protein (UCP1) expression promoting action. Therefore, it promotes energy consumption and has an anti-obesity effect. Further, such compounds are known to exist in natural products and have high safety. Furthermore, such a component can improve the stability of the compound by being in the form of a salt or the like, and can be stably blended into the composition, thereby improving the bioavailability and heat production. Improvement of protein expression promoting action is expected.

Here, the compound represented by the general formula (2) will be described. In the general formula (2), R ₆ , R ₇ , R ₉ and R ₁₀ are each independently a hydrogen atom or a carbon number of 1 to 4. R ₈ represents a hydroxyl group, an alkoxy group having an alkyl chain having 1 to 4 carbon atoms, a pentose or hexose linked by an ether bond, and X ⁻ represents an anion. R ₆ , R ₇ , R ₉ and R ₁₀ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Specific examples include a hydrogen atom, a methyl group, an ethyl group, a propyl group, A butyl group can be preferably exemplified, and a hydrogen atom and a methyl group are particularly preferable. R ₈ represents a hydroxyl group, an alkyl group having 1 to 4 carbon atoms, and represents a pentose or hexose linked by an ether bond. Specific examples include hydroxyl, methoxy, ethoxy, propyl Examples of pentoses bonded by an oxy group, a butyloxy group, and an ether bond include ribose, lyxose, xylos, arabinose, and apios. As the hexoses bonded, allose, glucose, tarose, gloss, artrose, mannose, galactose, idose and the like can be preferably exemplified. Preferred examples include a hydroxyl group, a group in which arabinose is bonded by an ether bond (arabinose residue), a group in which galactose is bonded by an ether bond (galactose residue), and the like. There is no particular limitation on the position at which the pentose or hexose binds to the ether, but in particular, in the case of pentose, the 4-position of the sugar chain is in the case of hexose. The 5 positions of the sugar chain are preferred. In addition, the anion is not particularly limited as long as it is a monovalent anion, but a chlorine ion is particularly preferable. Of the compounds represented by the general formula (2), free base forms, isomers thereof and / or pharmacologically acceptable salts thereof, more preferred are the general formula (3) or the general formula ( The compound represented by 4) can be preferably exemplified.

Here, the compound represented by the general formula (3) will be described. In the general formula (3), R ₁₁ , R ₁₂ , R ₁₃ and R ₁₄ are each independently a hydrogen atom or a carbon number of 1-4. And X ⁻ represents an anion. R ₁₁ , R ₁₂ , R ₁₃ and R ₁₄ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Specific examples include a hydrogen atom, a methyl group, an ethyl group, a propyl group, A butyl group can be suitably exemplified, and a hydrogen atom is particularly preferable. In addition, the anion is not particularly limited as long as it is a monovalent anion, but a chlorine ion is particularly preferable. Specific examples of the compound represented by the general formula (3) include 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-1-benzopyrylium chloride (cyanidine chloride). ), 2- (3,4-dihydroxyphenyl) -3,5-dihydroxy-7-methoxy-1-benzopyrylium chloride, 2- (3,4-dihydroxyphenyl) -3,7-dihydroxy-5-methoxy -1-benzopyrylium chloride, 2- (3,4-dihydroxyphenyl) -3-hydroxy-5,7-dimethoxy-1-benzopyrylium chloride, 2- (4-hydroxy-3-methoxyphenyl) -3 , 5,7-Trihydroxy-1-benzopyrylium chloride, 2- (4-hydroxy-3-methoxyphenyl) -3,5-dihydroxy-7- Toxi-1-benzopyrylium chloride, 2- (4-hydroxy-3-methoxyphenyl) -3,7-dihydroxy-5-methoxy-1-benzopyrylium chloride, 2- (4-hydroxy-3-methoxyphenyl) ) -3-Hydroxy-5,7-dimethoxy-1-benzopyrylium chloride, 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-1-benzopyrylium bromide, 2- (3 , 4-Dihydroxyphenyl) -3,5-dihydroxy-7-methoxy-1-benzopyrylium bromide, 2- (3,4-dihydroxyphenyl) -3,7-dihydroxy-5-methoxy-1-benzopyrylium Bromide, 2- (3,4-dihydroxyphenyl) -3-hydroxy-5,7-dimethoxy-1-benzopyrylium bromide 2- (4-hydroxy-3-methoxyphenyl) -3,5,7-trihydroxy-1-benzopyrylium bromide, 2- (4-hydroxy-3-methoxyphenyl) -3,5-dihydroxy- 7-methoxy-1-benzopyrylium bromide, 2- (4-hydroxy-3-methoxyphenyl) -3,7-dihydroxy-5-methoxy-1-benzopyrylium bromide, 2- (4-hydroxy-3- Methoxyphenyl) -3-hydroxy-5,7-dimethoxy-1-benzopyrylium bromide, 2- (3,4,5-trihydroxyphenyl) -3,5,7-trihydroxy-1-benzopyrylium chloride (Delphinidin chloride), 2- (3,4,5-trihydroxyphenyl) -3-hydroxy-5,7-dimethoxy-1-benzopyri Lithium chloride, 2- (3,4,5-trihydroxyphenyl) -3,5-dihydroxy-7-methoxy-1-benzopyrylium chloride, 2- (3,4,5-trihydroxyphenyl) -3, 7-dihydroxy-5-methoxy-1-benzopyrylium chloride, 2- (3,4-dihydroxy-5-methoxyphenyl) -3,5,7-trihydroxy-1-benzopyrylium chloride, 2- (3 , 4-Dihydroxy-5-methoxyphenyl) -3-hydroxy-5,7-dimethoxy-1-benzopyrylium chloride, 2- (3,4-dihydroxy-5-methoxyphenyl) -3,5-dihydroxy-7 -Methoxy-1-benzopyrylium chloride, 2- (3,4-dihydroxy-5-methoxyphenyl) -3,7-dihydroxy-5-methoxy -1-benzopyrylium chloride, 2- (4,5-dihydroxy-3-methoxyphenyl) -3,5,7-trihydroxy-1-benzopyrylium chloride, 2- (4,5-dihydroxy-3- Methoxyphenyl) -3-hydroxy-5,7-dimethoxy-1-benzopyrylium chloride, 2- (4,5-dihydroxy-3-methoxyphenyl) -3,5-dihydroxy-7-methoxy-1-benzopyri Rium chloride, 2- (4,5-dihydroxy-3-methoxyphenyl) -3,7-dihydroxy-5-methoxy-1-benzopyrylium chloride, 2- (4-hydroxy-3,5-dimethoxyphenyl)- 3,5,7-trihydroxy-1-benzopyrylium chloride, 2- (4-hydroxy-3,5-dimethoxyphenyl) -3- Roxy-5,7-dimethoxy-1-benzopyrylium chloride, 2- (4-hydroxy-3,5-dimethoxyphenyl) -3,5-dihydroxy-7-methoxy-1-benzopyrylium chloride, 2- ( 4-hydroxy-3,5-dimethoxyphenyl) -3,7-dihydroxy-5-methoxy-1-benzopyrylium chloride, 2- (3,4,5-trihydroxyphenyl) -3,5,7-tri Hydroxy-1-benzopyrylium bromide, 2- (3,4,5-trihydroxyphenyl) -3-hydroxy-5,7-dimethoxy-1-benzopyrylium bromide, 2- (3,4,5-tri Hydroxyphenyl) -3,5-dihydroxy-7-methoxy-1-benzopyrylium bromide, 2- (3,4,5-trihydroxyphenyl) -3,7 -Dihydroxy-5-methoxy-1-benzopyrylium bromide, 2- (3,4-dihydroxy-5-methoxyphenyl) -3,5,7-trihydroxy-1-benzopyrylium bromide, 2- (3 4-Dihydroxy-5-methoxyphenyl) -3-hydroxy-5,7-dimethoxy-1-benzopyrylium bromide, 2- (3,4-dihydroxy-5-methoxyphenyl) -3,5-dihydroxy-7- Methoxy-1-benzopyrylium bromide, 2- (3,4-dihydroxy-5-methoxyphenyl) -3,7-dihydroxy-5-methoxy-1-benzopyrylium bromide, 2- (4,5-dihydroxy- 3-methoxyphenyl) -3,5,7-trihydroxy-1-benzopyrylium bromide, 2- (4,5-dihydroxy-3- Toxiphenyl) -3-hydroxy-5,7-dimethoxy-1-benzopyrylium bromide, 2- (4,5-dihydroxy-3-methoxyphenyl) -3,5-dihydroxy-7-methoxy-1-benzopyri Rium bromide, 2- (4,5-dihydroxy-3-methoxyphenyl) -3,7-dihydroxy-5-methoxy-1-benzopyrylium bromide, 2- (4-hydroxy-3,5-dimethoxyphenyl)- 3,5,7-trihydroxy-1-benzopyrylium cubromide, 2- (4-hydroxy-3,5-dimethoxyphenyl) -3-hydroxy-5,7-dimethoxy-1-benzopyrylium bromide, 2, -(4-Hydroxy-3,5-dimethoxyphenyl) -3,5-dihydroxy-7-methoxy-1-benzopyrylium bromi 2- (4-hydroxy-3,5-dimethoxyphenyl) -3,7-dihydroxy-5-methoxy-1-benzopyrylium bromide, its isomers and / or pharmacologically acceptable salts thereof, Of these, 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-1-benzopyrylium chloride (cyanidine chloride), 2- (3,4 , 5-trihydroxyphenyl) -3,5,7-trihydroxy-1-benzopyrylium chloride (delphinidin chloride), its isomers and / or their pharmacologically acceptable salts.

Here, the compound represented by the general formula (4) will be described. In the general formula (4), R ₁₅ , R ₁₆ , R ₁₈ and R ₁₉ are each independently a hydrogen atom or a carbon number of 1 to 4. Wherein R ₁₇ represents a pentose or hexose linked by an ether bond, and X ⁻ represents an anion. R ₁₅ , R ₁₆ , R ₁₈ and R ₁₉ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Specific examples include a hydrogen atom, a methyl group, an ethyl group, a propyl group, Represents a butyl group, and among these, a hydrogen atom and a methyl group are particularly preferred. R ₁₇ represents a pentose or hexose linked by an ether bond, and examples of the pentose linked by an ether bond include ribose, lyxose, xylos, and arabino. Examples of hexoses to which amino acids, apioses and the like are bonded by ether bonds include allose, tarose, glucose, gloss, artrose, mannose, galacto- And groups such as hydroxy group, arabinose group bonded by ether bond (arabinose residue), and galactose group bonded by ether bond (galacto). -Residues) and the like can be preferably exemplified. There is no particular limitation on the position at which the pentose or hexose binds to the ether, but in particular, in the case of pentose, the 4-position of the sugar chain is in the case of hexose. The 5 positions of the sugar chain are preferred. In addition, the anion is not particularly limited as long as it is a monovalent anion, but a chlorine ion is particularly preferable. Specific examples of the compound represented by the general formula (4) include 2- (3,4-dihydroxyphenyl) -3- (β-D-galactopyranosyloxy) -5,7-dihydroxy-1 Benzopyrylium chloride (idinin, cyanidin 3-galactoside), 2- (3,4-dihydroxyphenyl) -3- (β-D-galactopyranosyloxy) -5-hydroxy-7-methoxy-1-benzo Pyrylium chloride, 2- (3,4-dihydroxyphenyl) -3- (β-D-galactopyranosyloxy) -7-hydroxy-5-methoxy-1-benzopyrylium chloride, 2- (4-hydroxy -3-methoxyphenyl) -3- (β-D-galactopyranosyloxy) -5,7-dihydroxy-1-benzopyrylium chloride, 2- (4-hydroxy 3-methoxyphenyl) -3- (β-D-galactopyranosyloxy) -5-hydroxy-7-methoxy-1-benzopyrylium chloride, 2- (4-hydroxy-3-methoxyphenyl) -3- (Β-D-galactopyranosyloxy) -7-hydroxy-5-methoxy-1-benzopyrylium chloride, 2- (3,4-dihydroxyphenyl) -3- (β-D-galactopyranosyloxy) ) -5,7-dihydroxy-1-benzopyrylium bromide, 2- (3,4-dihydroxyphenyl) -3- (β-D-galactopyranosyloxy) -5-hydroxy-7-methoxy-1- Benzopyrylium bromide, 2- (3,4-dihydroxyphenyl) -3- (β-D-galactopyranosyloxy) -7-hydroxy-5-methoxy-1-benzopi Rium bromide, 2- (4-hydroxy-3-methoxyphenyl) -3- (β-D-galactopyranosyloxy) -5,7-dihydroxy-1-benzopyrylium bromide, 2- (4-hydroxy- 3-methoxyphenyl) -3- (β-D-galactopyranosyloxy) -5-hydroxy-7-methoxy-1-benzopyrylium bromide, 2- (4-hydroxy-3-methoxyphenyl) -3- (Β-D-galactopyranosyloxy) -7-hydroxy-5-methoxy-1-benzopyrylium bromide, 2- (3,4-dihydroxyphenyl) -3- (β-D-galactopyranosyloxy) ) -5,7-dihydroxy-4H-1-benzopyran-4-one (querserin 3-glucoside), 2- (3,4-dihydroxyphenyl) -3- (β-D-) Lactopyranosyloxy) -5-hydroxy-7-methoxy-4H-1-benzopyran-4-one, 2- (3,4-dihydroxyphenyl) -3- (β-D-galactopyranosyloxy)- 7-hydroxy-5-methoxy-4H-1-benzopyran-4-one, 2- (3,4-dihydroxyphenyl) -3- (β-D-galactopyranosyloxy) -5,7-methoxy-4H -1-benzopyran-4-one, 2- (4-hydroxy-3-methoxyphenyl) -3- (β-D-galactopyranosyloxy) -5,7-dihydroxy-4H-1-benzopyran-4- On, 2- (4-hydroxy-3-methoxyphenyl) -3- (β-D-galactopyranosyloxy) -5-hydroxy-7-methoxy-4H-1-benzopyran-4-one, 2- ( 4 -Hydroxy-3-methoxyphenyl) -3- (β-D-galactopyranosyloxy) -7-hydroxy-5-methoxy-4H-1-benzopyran-4-one, 2- (4-dihydroxy-3- Methoxyphenyl) -3- (β-D-galactopyranosyloxy) -5,7-methoxy-4H-1-benzopyran-4-one, its isomers and / or their pharmacological salts are preferred Among these, in particular, 2- (3,4-dihydroxyphenyl) -3- (β-D-galactopyranosyloxy) -5,7-dihydroxy-1-benzopyrylium chloride (ideain, Cyanidin 3-galactoside), 2- (3,4-dihydroxyphenyl) -3- (β-D-galactopyranosyloxy) -5,7-dihydroxy-4H-1-benzopyran-4- Preferable examples include ON (querserin 3-glucoside), its isomers and / or pharmacologically acceptable salts thereof.

Here, the compound represented by the general formula (5) will be described. In the general formula (5), R ₂₀ and R ₂₁ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. ₂₂ represents quinic acid bonded by a hydroxyl group, an alkoxy group having an alkyl chain having 1 to 4 carbon atoms, and an ether bond. R ₂₀ and R ₂₁ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Specific examples include a hydrogen atom, a methyl group, an ethyl group, a propyl group, and a butyl group. Of these, particularly preferred are a hydrogen atom and a methyl group. R ₂₂ represents a hydroxyl group, an alkoxy group having an alkyl chain having 1 to 4 carbon atoms, quinic acid bonded by an ether bond, and specific examples include a hydroxyl group, a methoxy group, an ethoxy group, a propyloxy group, 2-Quinic acid, 3-quinic acid, 4-quinic acid, 5-quinic acid having an ester structure in which an ether bond is formed with a butyloxy group, or a hydroxyl group at the 2, 3, 4 or 5-position of quinic acid Etc. can be suitably exemplified. Among these, a hydroxyl group or 5-quinic acid can be preferably exemplified. Specific examples of the compound represented by the general formula (5) include cinnamic acid, methyl cinnamate, ethyl cinnamate, propyl cinnamate, butyl cinnamate, and 2- (3,4-dihydroxycinnamoyl) quina. Acid, 2- (3-methoxy-4-hydroxycinnamoyl) quinic acid, 3- (3,4-dihydroxycinnamoyl) quinic acid, 3- (3-methoxy-4-hydroxycinnamoyl) quinic acid, 4- (3,4-dihydroxycinnamoyl) quinic acid, 4- (3-methoxy-4-hydroxycinnamoyl) quinic acid, 5- (3,4-dihydroxycinnamoyl) quinic acid (chlorogenic acid), 5- (3 -Methoxy-4-hydroxycinnamoyl) quinic acid, its isomers and / or pharmacologically acceptable salts thereof can be preferably exemplified, and among these, in particular, 5- (3,4-dihydroxy) Cinnamoyl) quinic acid (chlorogenic acid), its isomers and / or a pharmaceutically acceptable salt thereof pharmacologically is suitably be exemplified.

Cal component or a heat-producing proteins present in brown adipose cells in vivo, especially, excellent UCP1 expression enhancing action, I hereinafter, energy - to promote consumption, has anti-obesity effect. In the present invention, the effect of promoting the expression of the thermogenic protein means that the quantitative value of the band corresponding to the thermogenic protein is the quantitative value of the control in the thermogenic protein expression promoting test using rat brown adipocytes described later. In comparison with the above, it means a high case, and more preferably 1.5 times higher than the quantitative value of the control. UCP1 is a membrane protein that exists in the mitochondria of brown adipocytes and plays a role in maintaining body temperature. In order to eliminate the UCP1, proton concentration gradient in a short circuit, when it is activated, the chemical energy of the oxidized substrate is not used for ATP synthesis but is converted to heat. The heat generated therefrom is used to maintain body temperature and dissipate surplus energy and is consumed as energy. In addition, it has been confirmed that such components are present in natural plants, for example, plants such as Azalea genus Bruberry, Rosaceae aronia aronia, and used for cosmetics, foods, etc. Since it has a proven track record and high safety has been confirmed, it is preferably used for foods, pharmaceuticals, cosmetics and the like. In order to achieve such an effect, the content of the compound in the slimming composition of the present invention is such that the compound represented by the general formula (1), its isomer and / or pharmacologically acceptable thereof. 1 to 2 or more types selected from the salts to be prepared are preferably contained in a total amount of 0.001% by mass to 20% by mass, more preferably 0.005% by mass to 10% by mass, More preferably, it is 0.01 mass%-5 mass%, and more preferable. This is because if the amount is too small, the above-mentioned effect may not be achieved, and if the amount is too large, the effect may reach a limit and the degree of freedom of the system may be impaired.

Compound of the formula (1) such as this, its isomers and / or a pharmaceutically acceptable salt thereof pharmacologically, since also naturally exist, extracted from natural products, purified (For example, refer nonpatent literature 3). In addition, a partial structure of a compound isolated and purified from such a natural product can be chemically modified according to a conventional method to lead to a related compound. Preferred examples of the compound represented by the general formula (1), its free base, its isomer and / or pharmacologically acceptable salt thereof include compounds represented by compounds 1 to 6 described below. I can do it. These compounds are known to be contained in an extract of a plant belonging to the genus Rosaceae, and examples of the plant belonging to the genus Aronia belonging to the family Rosaceae include aronia. As a plant part used for preparing an aronia extract, a fruit can be preferably exemplified. The Aronia genus Aronia is a deciduous shrub that originates in North America, and its fruit contains a large amount of anthocyanins and is used in foods such as jam, fruit wine, and ice cream. In Japan, aronia is produced as edible or herbal medicine in Hokkaido, etc., and is marketed in the form of food, herbal medicine or extract. In the examples of the present invention, Japanese aronia was used. In the extraction, it is preferable to process the fruit or dried product in advance so as to improve the extraction efficiency by crushing or chopping. For the extract, 1 to 30 parts by mass of a solvent is added to 1 part by mass of the fruit or its dried product, and it is immersed for several hours to several days at room temperature and for several hours at a temperature near the boiling point. After the immersion, the solution can be cooled to room temperature, insoluble matter can be removed if desired, and then the solvent can be removed by concentration under reduced pressure. Thereafter, fractionation and purification can be performed by column chromatography packed with silica gel or an ion exchange resin to obtain a desired extract. In the present invention, the extract means a generic name of the extract itself, a fraction obtained by fractionating and purifying the extract, the extract or fraction, and the solvent-removed product of the purified product. In addition, in the present invention, the substance having the effect of promoting the expression of thermogenic protein means the quantitative value of the band corresponding to the thermogenic protein ( UCP1) in the experiment of promoting the expression of thermogenic protein in rat brown adipocytes described later. Is higher than the quantitative value of the control.

<The composition for slimming of this invention>
The slimming composition of the present invention contains a heat-producing protein expression promoter comprising a compound represented by the general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof. Features. In the present invention, the substance having the effect of promoting the expression of the heat-producing protein refers to the quantitative value of the band corresponding to the heat-producing protein ( UCP1) in the experiment of promoting the expression of the heat-producing protein in rat brown adipocytes described later. It means a case where it is higher than the quantitative value of the control, and more preferably, it is higher than 1.5 times as compared with the quantitative value of the control. In the slimming composition of the present invention, the compound represented by the general formula (1), its isomer and / or its pharmacologically acceptable salt are the compound represented by the general formula (1), its Of the isomers and / or pharmacologically acceptable salts thereof, one or a combination of two or more can be used. The compound represented by the general formula (1), isomers thereof and / or pharmacologically acceptable salts thereof may be directly blended into a slimming composition, or represented by the general formula (1). The compound, its isomer and / or pharmacologically acceptable salt thereof can also be formulated as an extract of the genus Aronia aronia. The extract of the present invention is a generic term for the extract itself, a fraction obtained by fractionating and purifying the extract, the extract or fraction, and a solvent-removed product of the purified product. Inclusion of such a compound represented by the general formula (1), a isomer thereof and / or a pharmacologically acceptable salt thereof in the slimming composition of the present invention It is more preferable in terms of increasing the degree of freedom.

Also, optional ingredients when the formulation of the compound represented Rosaceae aronia extract obtained from Aronia containing the general formula (1), used in the formulation of such ordinary foods, pharmaceuticals, cosmetics Can be contained. Examples of such optional components include oral excipients such as excipients such as lactose and white sugar, binders such as starch, cellulose, gum arabic, and hydroxypropyl cellulose, carboxymethyl cellulose, Disintegrants such as sodium and carboxymethylcellulose calcium, surfactants such as soy lecithin and sucrose fatty acid ester, sweeteners such as malt and sorbitol, sour agents such as citric acid, phosphates, etc. Buffering agents, film forming agents such as shellac and zein, lubricants such as talc and wax, glidants such as light anhydrous silicic acid and dry aluminum hydroxide gel, diluents such as physiological saline and aqueous glucose solution, Suitable examples include flavoring agents, coloring agents, bactericides, preservatives, and fragrances. If it is a composition for transdermal administration, hydrocarbons such as squalane, petrolatum and microcrystalline wax, esters such as jojoba oil, carnauba wax, octyldodecyl oleate, triglycerides such as olive oil, beef tallow and coconut oil , Fatty acids such as stearic acid, oleic acid, retinoic acid, higher alcohols such as oleyl alcohol, stearyl alcohol, octyl decanol, anionic interfaces such as sulfosuccinic acid ester and sodium polyoxyethylene alkyl sulfate Activators, amphoteric surfactants such as alkylbetaine salts, cationic surfactants such as dialkylammonium salts, sorbitan fatty acid esters, fatty acid monoglycerides, their polyoxyethylene adducts, polyoxyethylene alkyl ethers, poly Oxyethylene Nonionic surfactants such as fatty acid esters, polyhydric alcohols such as polyethylene glycol, glycerin, 1,3-butanediol, thickening / gelling agents, antioxidants, UV absorbers, colors Agents, preservatives, powders and the like. Manufacture can be done without difficulty by treating these components according to conventional methods.

As the slimming composition of the present invention, pharmaceuticals, cosmetics, foods, beverages and the like can be suitably exemplified, and since they can be taken on a daily basis, they are preferably applied to foods, cosmetics and the like. The administration route can be either oral administration or transdermal administration. For the purpose of detoxification (detox), oral administration with high efficiency in reaching the relevant organ is adopted, and forms of oral administration compositions such as foods Is preferably adopted.

（化合物２、イデアイン、Ideain（Cyanidin ３−galactoside））

(Compound 2, Idea Lee down, Ideain (Cyanidin 3-galactoside) )

<Expression promotion test of thermogenic protein in rat brown adipocytes>
The compound 1-6 purified by the above method, its isomers and / or their pharmacologically acceptable salts, were evaluated for the thermogenic protein expression promoting action. However, since the compounds 1 to 4 can be stored as salts that can be stably stored by treatment with hydrochloric acid, the hydrochlorides of the compounds 1 to 4 were used. Moreover, the heat-producing protein expression promotion effect of the extract (ethanol fraction) obtained from the Rosaceae Allonia genus Aronia obtained according to the said method was evaluated.
Culturing rat preadipocytes were differentiated brown adipocytes. The brown adipocytes are treated with a medium containing compounds 1 to 6 and an Aronia genus Aronia extract (ethanol fraction) obtained according to the method described in Test Example 1, and then the protein is extracted. UCP1 expression was detected by Western blotting. The detected UCP1 band was quantified. What was processed with the culture medium which does not contain the said compound and extract was made into the control, and when the quantitative value of a band was higher than control, it was set as the thing which has a heat production protein ( UCP1 ) expression promotion effect | action. The results are shown in FIGS.

Of compounds 1-6 and Rosaceae aronia extract obtained from Aronia (ethanol - Le fraction) is seen to have a heat production protein expression promoting effect. From this, it can be seen that the compounds 1 to 6 and the extract (ethanol fraction) obtained from the Rosaceae Aronia genus Aronia have an obesity suppressing effect due to the heat-producing protein expression promoting action.

According to the formulation shown in the following, to prepare a lotion. That is, the prescription ingredients were stirred and solubilized at room temperature to obtain a lotion. Using this skin lotion, three people from Panera-1 group suffering from obesity were asked to evaluate the effect of the slimming action on the abdomen twice a day for one month and morning and evening. The evaluation criteria are the change of the face line (decrease in bulging) as the observation point, and score 2: marked improvement, score 1: obvious improvement, score 0.5: slight improvement, score 0: no improvement It was. The average score was 0.95. A slimming effect was observed in the lotion containing Compound 1 having the effect of promoting the expression of the heat-producing protein of the present invention.

Chestnut according to the formulation shown in the following - to produce a beam. That is, a, b, and c are heated and dissolved at 80 ° C. respectively, and b is gradually added to emulsify and further emulsified with c, and then the emulsion particles are homogenized by a homomixer and cooled to obtain a cream. It was. Using this cream, the slimming effect was evaluated by the method described in Example 5. The average score was 0.89. This cream had an excellent slimming effect.

Claims (15)

A thermogenic protein expression promoter comprising a compound represented by the following general formula (1), an isomer thereof and / or a pharmacologically acceptable salt thereof.

(1)
[Wherein, R ₁ and R ₂ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₃ represents a hydrogen atom or a linear or branched alkyl chain having 1 to 4 carbon atoms. Represents a linear or branched alkyl or alkenyl group in which an alkoxy group, a hydrogen atom or a carbon atom may be substituted with a hetero atom, and R ₄ has a hydrogen atom, a hydroxyl group, or an alkyl chain having 1 to 4 carbon atoms. Represents an pentose or hexose linked by an alkoxy group or an ether bond, and R ₅ represents a hydrogen atom or a straight, branched or cyclic group in which a hydrogen atom or a carbon atom may be substituted with a hetero atom. Represents an alkyl group. However, R ₃ and R ₅ may be bonded to each other to form a cyclic structure. n represents an integer of 0 or 1. ] The compound represented by the general formula (1) is a compound represented by the following general formula (2), its free base, its isomer and / or a pharmacologically acceptable salt thereof. The heat-producing protein expression promoter according to claim 1, characterized in that

(2)
[Wherein R ₆ , R ₇ , R ₉ and R ₁₀ each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₈ represents a hydroxyl group or an alkyl chain having 1 to 4 carbon atoms. Represents an alkoxy group having a pentose or hexose linked by an ether bond, and X ⁻ represents an anion. ] The compound represented by the general formula (2) is a compound represented by the following general formula (3), its free base, its isomer and / or a pharmacologically acceptable salt thereof. The heat-producing protein expression promoter according to claim 2 , characterized in that

(3)
[Wherein, R ₁₁ , R ₁₂ , R ₁₃ and R ₁₄ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and X ⁻ represents an anion. ] The compound represented by the general formula (2) is a compound represented by the following general formula (4), its free base, its isomer and / or a pharmacologically acceptable salt thereof. The heat-producing protein expression promoter according to claim 2 , characterized in that

(4)
[Wherein, R ₁₅ , R ₁₆ , R ₁₈ and R ₁₉ each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₁₇ represents a pentose linked by an ether bond or Represents a hexose sugar, and X ⁻ represents an anion. ] 5. The pentose or hexose in the compounds represented by the general formulas (1) , (2) and (4) is arabinose or galactose. Or 4. The heat-producing protein expression promoter according to 4. The compound represented by the general formula (1) is a compound represented by the following general formula (5), an isomer thereof and / or a pharmacologically acceptable salt thereof, Item 2. The heat-producing protein expression promoter according to Item 1.

(5)
[Wherein, R ₂₀ and R ₂₁ each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and R ₂₂ represents a hydroxyl group, an alkoxy group having an alkyl chain having 1 to 4 carbon atoms, or ether. It represents quinic acid bound by a bond. ] The heat production protein expression promoter, cyanidin (cyanidin), Ideain (Ideain), cyanidin 3- arabinoside (Cyanidin 3-arabinoside), delphinidin (Delphinidine), quercetin 3- galactoside (Quercetin 3-galactoside), chlorogenic acid (C hlorogenic acid) and / or, characterized in that their pharmacologically acceptable salts, heat production protein expression promoting agent according to any one of claims 1 to 6. The heat production protein expression promoter, uncoupling protein 1 (uncoupling protein1: abbreviation UCP1), characterized in that the expression promoter, heat production protein expression promoting according to any one of claims 1 to 7 Agent. One selected from heat production protein expression promoting agent according to any one of claims 1 to 8 or characterized by containing two or more kinds, composition for slimming. The composition for slimming according to claim 9, wherein the heat-producing protein expression promoter is contained as an essence of a plant belonging to the genus Aroniaceae. The composition for slimming according to claim 10 , wherein the plant belonging to the genus Rosaceae is an Aronia belonging to the family Rosaceae. The composition for slimming according to any one of claims 9 to 11, wherein the heat-producing protein expression promoter is contained in an amount of 0.001% by mass to 20% by mass with respect to the total amount of the composition. The composition for slimming according to any one of claims 9 to 12, wherein the composition is an orally administered composition. The composition for slimming according to any one of claims 9 to 13, wherein the composition is food, medicine or cosmetic. A method for producing a slimming composition containing a heat-producing protein expression promoter , wherein a plant belonging to the genus Aroniaceae is selected, a fruit part is collected, extracted with a polar solvent, and fractionally purified. A production method comprising obtaining a fraction containing a flavonoid and an aglycon thereof, confirming the heat-producing protein expression promoting action in the fraction, and then blending it into the composition.