JP2010037245A - Composition suitable for metabolic activation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a means for elevating intracellular glutathione level for increasing substance metabolism rate. <P>SOLUTION: This composition contains (1) a compound represented by formula [1]: NHR((CH<SB>2</SB>)<SB>n</SB>-NR-(CH<SB>2</SB>)<SB>n</SB>)<SB>m</SB>NHR (wherein a plurality of Rs are monoamine constituting units and are each independently a hydrogen atom or a phenylpropenoyl(3-phenylprop-2-en-1-oyl) group wherein an aromatic hydrogen atom is optionally substituted with a hydroxy group or a 1-4C alkyloxy group) and (2) an extract of a blood-replenishing or blood-activating herbal medicine. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a composition such as food or cosmetics having a metabolic activation effect.

  In recent years, the idea that bioaccumulation of toxic substances present in the environment has caused various diseases has spread widely, and the concept of detoxification in biological systems is spreading to the private sector. (For example, see Patent Document 1, Patent Document 2, Patent Document 3, and Patent Document 4). In addition, although it is somewhat different from the concept of detox circulated in the private sector, it means the in vitro discharge of insecticides taken through food, toxic foreign substances generated in vivo such as amyloid protein, etc. Detox is an important concept in the field of medical science. (For example, see Non-Patent Document 1 and Non-Patent Document 2) The concept of extracorporeal release of such toxic substances or insoluble substances does not begin in modern medicine, but also exists in traditional Chinese medicine. In other words, there are already known herbal medicines that promote the action of the lysate that promotes the discharge of the generated insoluble matter and toxic substances, and the action of the active blood and the supplementary blood that detoxify the produced toxic substances. Furthermore, such herbal medicines are used to alleviate allergies and soothe inflammation (see, for example, Patent Document 5 and Patent Document 6). However, no study has been conducted so far to connect this kind of Kampo philosophy with the modern concept of poisoning, and this kind of connection can also provide a more effective defense against toxic substances. unknown.

  In recent years, the concept of detox in Western medicine has attracted attention for metabolic activation, in particular, conjugation of toxic substances by glutathione and promotion of its elimination. For this reason, the search of the component which accelerates | stimulates the synthesis | combination of glutathione in the living body, and the component which accelerates | stimulates the production | generation of a glutathione conjugate is performed actively. As a component having such an action, for example, a root extract such as chicory of the asteraceae family has been found. Such a component has an effect of increasing the activity of glutathione-S-transferase, thereby conjugating reduced glutathione with a toxic substance to promote its in vitro elimination (see, for example, Patent Document 7). In addition, a method for activating transglutaminase and increasing glutathione levels has been devised, and an extract of evening primrose has been found as such a material (see, for example, Patent Document 8). Furthermore, although the mechanism is unknown, a technique for improving the intracellular glutathione level by using a glycoside contained in Ketsumeishi is also known (see, for example, Patent Document 9). However, the rapid change of glutathione level is not realized even by such means, and the activation of transglutaminase is not very effective due to depletion of reduced glutathione because the level rise is small. In order to promote metabolic activation, it has been recognized that it is first important to increase glutathione levels in vivo. The significance of developing glutathione level enhancers lies here.

  On the other hand, polyamines such as spermidine and spermine themselves have acne and atopic dermatitis inhibitory action (see, for example, Patent Document 10) and skin pigmentation inhibitory action (see, for example, Patent Document 11). It is known. Also, polyamine aromatic amides (phenylpropenoyl polyamine derivatives) are known to exist in plants, but there are no reports on their pharmacological effects (see, for example, Non-Patent Document 3). ).

JP 2007-125270 A Japanese Patent Laid-Open No. 03-127736 JP 2001-172192 A JP 2002-125604 A Japanese Patent Application Laid-Open No. 08-40922 JP 2000-103718 A JP 2005-535314 A JP 2004-91376 A JP 2004-125604 A Japanese National Patent Publication No. 9-501925 Special table 2008-519022 gazette Poupardin R. et.al., Insect Biochem Mol Biol. 2008; 38 (5): 540-51. Sundaram R.K. et.al., Curr Alzheimer Res. 2008; 5 (1): 26-32. Stefan B. et.al., Nat. Prod. Rep., 2005, 22, 647-658.

  The present invention has been made under such circumstances, and it is an object of the present invention to provide a technique for enhancing metabolism in a living body, and thereby to improve the protective power against harmful substances in the living body.

In view of such a situation, the present inventors have sought for a technique for enhancing metabolism in the living body, and as a result of intensive research efforts, 1) phenylpropenoyl (propane) represented by the following general formula (1) Intracellular glutathione by orally or transdermally administering a composition containing 2-en-1-yl) polyamine derivative and / or a salt thereof and 2) an extract of a supplementary blood or active blood crude drug The inventors have found that the level of substance metabolism can be improved by improving the level, and the invention has been completed. That is, the present invention is as follows.
<1> 1) A composition comprising a phenylpropenoylpolyamine derivative represented by the following general formula (1) and / or a salt thereof, and 2) an extract of a supplementary blood or a live blood crude drug.

一般式（１）
（但し、式中、Ｒはモノアミン構成単位でそれぞれ独立した、水素原子又はヒドロキシ基若しくはＣ１〜４のアルキルオキシ基で芳香族水素原子が置換されていても良いフェニルプロペノイル（３−フェニルプロパン−２−エン−１−ノイル）基を表し、ポリアミン構成単位において少なくとも１つのＲはヒドロキシ基若しくはＣ１〜４のアルキルオキシ基で芳香族水素原子が置換されていても良いフェニルプロペノイル基であり、ｍは１〜５の整数を表し、ｎはモノアミン構成単位でそれぞれ独立した２〜５の整数を表す。）

General formula (1)
(However, in the formula, R is a monoamine structural unit, each of which is independently a hydrogen atom, a phenyl group or an aromatic hydrogen atom substituted with a hydroxy group or a C1-4 alkyloxy group (3-phenylpropane- 2-ene-1-noyl) group, and in the polyamine structural unit, at least one R is a phenylpropenoyl group in which an aromatic hydrogen atom may be substituted with a hydroxy group or a C1-4 alkyloxy group, m represents an integer of 1 to 5, and n represents an integer of 2 to 5 each independently in a monoamine structural unit.)

<2> The composition according to <1>, wherein the phenylpropenoyl (3-phenylpropan-2-en-1-noyl) polyamine derivative is tricoumaroyl spermidine or tetracoumaroyl spermine. .

トリクマロイルスペルミジン

Trikumaroyl spermidine

テトラクマロイルスペルミン

Tetracoumaroylspermine

<3> The above-mentioned supplemental blood or active blood crude drugs are Senkyu, Tanjin, Keiketto, Motousei, Engosaku, Turmeric, Kyodo, Yakumo Sou, Juwishi, Takuran, Ryoshouka, Gecka, Sakubai, Shikarak, Sekishak, Tonin, Kouka, Zanjuga, It is characterized by being selected from the following: Sangyo, Nyuko, Motsuyaku, Goshutsu, Ohurugyo, Rorotsu, Ryukid, Lactocuda, Keckets, Soboku, Kyusei, Goreishi, Garyoushi, Pangolin, Sweets, Shachu, Sanyotsu, Goyo and Utan <1> or the composition according to <2>.
<4> The above-mentioned extract of supplemented blood or active blood crude drug is an extract obtained by extracting a crude drug with water, alcohol or a mixture thereof, or a fraction purified product of the extract, <1> ~ <3> The composition according to any one of the above.
<5> The composition according to any one of <1> to <4>, which is a composition for metabolic activation.
<6> The composition according to any one of <1> to <5>, wherein the composition is a food or a cosmetic.

  According to the present invention, the intracellular glutathione level can be increased to increase the rate of substance metabolism.

<1> Polyamine derivative which is an essential component of the composition of the present invention The composition of the present invention contains the polyamine derivative represented by the general formula (1) and / or a salt thereof. In the general formula (1), R is a monoamine constituent unit, each independently a hydrogen atom or a phenylpropenoyl (propan-2-phenyl group) optionally substituted with a hydroxy group or a C1-4 alkyloxy group. En-1-yl) group, and at least one R in the polyamine structural unit is a phenylpropenoyl (propan-2-ene) in which an aromatic hydrogen atom may be substituted with a hydroxy group or a C1-4 alkyloxy group -1-yl) group, m represents an integer of 1 to 5, and n represents an integer of 2 to 5 each independently in a monoamine constituent unit. Examples of the phenylpropenoyl group in which the aromatic hydrogen atom may be substituted with a hydroxy group or a C1-4 alkyloxy group in the group represented by R include a 3- (2-hydroxyphenyl) propenoyl group, 3- ( 3-hydroxyphenyl) propenoyl group, coumaroyl group (3- (4-hydroxyphenyl) propenoyl group), 2-methoxycoumaroyl group, 3- (2-hydroxy-4-methoxyphenyl) propenoyl group, 3- (2, A 4-dihydroxyphenyl) propenoyl group, a 3- (2,4-dimethoxyphenyl) propenyl group and the like can be preferably exemplified, and a coumaroyl group is particularly preferable among them. The polyamine derivative which is an essential component of the composition of the present invention has at least one of these groups per molecule. Preferable examples of the polyamine serving as the substrate to be held include spermine and spermidine. Such polyamine derivatives can be produced by reacting commercially available polyamines such as spermidine and spermine with a carboxylic acid such as coumarin in the presence of a peptide synthesis reagent such as DCC. At this time, a polyamine derivative in which all amino groups are acylated can be obtained by using a large excess of carboxylic acid and equivalent amount of DCC for the amino group in the reaction. A polyamine derivative having a free amino group can also be obtained by adjusting the amount of carboxylic acid. A polyamine derivative having a free amino group can also be obtained by hydrolyzing a polyamine derivative in which all amino groups are acylated with an enzyme such as peptidase.

  Since such a polyamine derivative is also present in nature, it can be extracted from a natural product and purified. For example, polyamine derivatives based on spermidine as a polyamine base are present in flower buds of plants belonging to the family Rosaceae, and polyamine derivatives based on spermine are present, for example, in the florets of plants belonging to the genus Chrysanthemum. In order to obtain the polyamine derivative represented by the general formula (1) from these plants for the composition of the present invention, for example, water, alcohol such as ethanol or 1,3-butanediol or a mixture thereof. If necessary, the extraction solvent is removed by concentration under reduced pressure or the like, ion exchange resin such as Diaion (registered trademark), silica gel, octadodecyl silylated silica gel or the like as a carrier, and column chromatography, It can also be purified. If a specific technique is shown, a solvent of 1 to 20 times the amount of a plant is added at the time of extraction, and for a few days at room temperature or for several hours in a solvent at a temperature near the boiling point, the plant or its processing The product can be immersed, filtered or the like to remove insoluble matter, and then the solvent is removed by vacuum concentration or lyophilization, if desired, followed by fractionation, purification, etc., if desired. At this time, if the polyamine derivative is sufficiently contained in the purified extract or the solvent-removed product, it can be used in the form of an extract without isolating the polyamine derivative.

Of the polyamine derivatives represented by the general formula (1) thus obtained, preferred examples thereof include the following compounds. Of these, tetracoumaroyl spermine is particularly preferred.
Monocoumaroyl Spermidine Dicoumaroyl Speraldine Tricoumaroyl Spermidine Monocinnamoyl Spermidine Dicine Namoyl Spermidine Tricinnamoyl Spermidine Monocoumaroyl Spermine Dicoumaroyl Spermine Tricoumaroyl Spermine Tetracouloyl Spermine Monocinnamoyl Spermine Dicinnamoyl Spermine Tricinna Moyl spermine tetracinnamoyl spermine

  The polyamine derivative thus obtained can be used as it is, or can be treated with an acid to be converted into a salt form and used as a salt. Preferred examples of the salt include mineral acid salts such as hydrochloride, sulfate, nitrate, phosphate, and carbonate, and organic acid salts such as oxalate, citrate, lactate, and tartrate. .

  Such polyamine derivatives or salts thereof can improve the total amount of glutathione produced by peptide bonding of cysteine, glutamic acid and glycine in living cells. Such glutathione has an action of reacting with a toxic compound via glutathione-S-transferase to form a conjugate and promoting ex vivo elimination. That is, it has the effect of improving the level of glutathione, which is an essential component of the composition of the present invention, and promoting metabolic excretion.

  In order to achieve such an effect, the polyamine derivative represented by the general formula (1) and a salt thereof are 0.001 to 10% by mass, more preferably 0.01 to 5% by mass, based on the total amount of the composition. The composition is preferably administered at 10 to 10,000 mg per day, more preferably 20 to 5000 mg. The number of administration can be used without any particular limitation, and is preferably 1 to 4 times.

<2> Extract of a hemopoietic / active blood crude drug that is an essential component of the composition of the present invention The composition of the present invention is characterized by containing an extract of the hemopoietic / active blood crude drug as an essential component. Here, the extract is a processed product obtained by drying, chopping, and pulverizing a crude drug, an extract obtained by extracting a processed product or a plant of the crude drug with a solvent, an extracted solvent-removed product obtained by removing the solvent of the extract, This is a generic term for a fraction-purified product obtained by fractionating and purifying an extract or an extracted solvent-removed product by column chromatography or liquid-liquid extraction, a fraction-purified solvent-removed product obtained by removing the solvent from the fraction-purified product, and the like.

  As a supplementary blood and active blood crude drug, those according to the Kampo classification can be used, and specifically, Senkyu, Tanjin, Caquette, Motousei, Engosaku, Turmeric, Kyoou, Yakumoso, Juwishi, Taklang, Ryoshouka, Geckika, Sakubaika, Shikaraku , Sekisha, Tonin, Kou, Bankou, Gatsutsu, Sangyo, Nyukou, Motsuyaku, Goshitsu, Ouhurugyou, Lorotsu, Ryukdo, Lactocuda, Ketsutsu, Sokoku, Kyusei, Goreishi, Ganchoushi, Ganchou, Chutoku, Chutoku, Chutoku, Syuyu Preferred examples can be given. As these extracts, it is preferable to use a solvent-removed product of the extract extracted with ethanol having a water content of 10 to 70%. Production examples are shown below.

<Production Example 1>
Add 1 L of 50% water-containing ethanol to 100 g of rhizome (Ciraceae), reflux for 2 hours, filter after cooling to remove insolubles, concentrate under reduced pressure, and then freeze-dry to obtain a gypsum extract (Extract 1). 1.3g was obtained as amorphous.

<Production Example 2>
Add 1L of 50% aqueous ethanol to 100g root of Tanjin (Lamiaceae), reflux for 2 hours, cool and filter to remove insolubles, concentrate under reduced pressure, and then freeze-dry to obtain Tanjin extract (Extract 2). 1.7g was obtained as amorphous.

<Production Example 3>
Add 1 L of 50% water-containing ethanol to 100 g of above-ground part (vine) of keiket (leguminous), reflux for 2 hours, filter after cooling to remove insolubles, concentrate under reduced pressure, and then freeze-dry to keiquette extract 0.9 g of (Extract 3) was obtained as amorphous.

<Production Example 4>
1 L of 50% aqueous ethanol was added to 100 g of roots of Amaliaceae (Lepidaceae), refluxed for 2 hours, cooled, filtered to remove insoluble matters, concentrated under reduced pressure, and then freeze-dried to obtain an extract of Moutosei (Extract 4). ) Was obtained as amorphous.

<Production Example 5>
Add 1L of 50% water-containing ethanol to 100g tuber of Engosaku (Papaveraceae), reflux for 2 hours, cool and filter to remove insoluble matter, concentrate under reduced pressure, and then freeze-dry to make Engosaku extract amorphous (Extract 5) ) Was obtained as 1.2).

<Production Example 6>
Add 1 L of 50% aqueous ethanol to 100 g of turmeric (Gingeraceae) rhizome, reflux for 2 hours, cool and filter to remove insolubles, concentrate under reduced pressure, and then freeze-dry to obtain turmeric extract (Extract 6). 1.6g was obtained as amorphous.

<Production Example 7>
Add 1 L of 50% aqueous ethanol to 100 g of rhododendron (Leguminosae; Clara), reflux for 2 hours, cool and filter to remove insolubles, concentrate under reduced pressure, and then freeze-dry to extract Kyoou extract (Extract 7) ) Was obtained as amorphous.

<Production Example 8>
1L of 50% aqueous ethanol was added to 100 g of the above ground portion of Yakusou (Lamiaceae), refluxed for 2 hours, filtered after cooling to remove insoluble matters, concentrated under reduced pressure, and then freeze-dried to extract Yakusou extract (Extract 8). ) Was obtained as amorphous.

<Production Example 9>
Add 1 L of 50% aqueous ethanol to 100 g of Takeran (Lamiaceae), reflux for 2 hours, cool, filter to remove insolubles, concentrate under reduced pressure, and then freeze-dry to obtain Takelan extract (Extract 9 ) Was obtained as amorphous.

<Production Example 10>
Add 100 ml of 50% aqueous ethanol to 10 g of stigma and stigma of Bankouka (Iridaceae), reflux for 2 hours, cool, filter to remove insolubles, concentrate under reduced pressure, and then freeze-dry to extract Bankouka extract (Extract 10). ) Was obtained as amorphous.

  The thus-obtained extract of supplementary blood and active blood crude drug has the effect of increasing the rate at which toxic substances present in the body are converted into metabolites with low toxicity. Such an effect is considered to improve the glutathione level, increase the amount of reduced glutathione, and promote the conjugate formation. Such an action of improving the glutathione level is synergistically enhanced in the presence of the polyamine derivative of the general formula (1). In order to exert such an action, the composition of the present invention preferably contains 0.001 to 30% by mass of the above-mentioned supplementary / active blood crude drug extract with respect to the total amount of the composition. It is more preferable to contain 10 mass%. The amount is preferably 1 to 1000 times the total amount of the polyamine derivative and its salt.

<3> Composition of the Present Invention The composition of the present invention is characterized by containing the polyamine derivative and / or a salt thereof, and a blood-recovery / active blood crude drug extract. By adopting such a configuration, the composition of the present invention has an action of enhancing a metabolic function for excretion of an unfavorable component having toxicity in a living body. Therefore, it is useful for suppression of an unfavorable physiological reaction caused by accumulation of such harmful substances and prevention of organic of the physiological reaction. Such harmful substances include, for example, food additives such as residual agricultural chemicals and preservatives that have been ingested at the time of ingestion of foods, peroxidation substances produced by oxidation of ingested oils and fats, and inflammation produced by microorganisms. A substance etc. can be illustrated suitably. Unfavorable physiological reactions induced by these include inflammation that is difficult to extinguish, such as atopic dermatitis, complex reaction of inflammation, such as comedones, and skin morphological changes, and allergies associated with decreased organ function, such as asthma It has effects such as improvement of symptoms of heavy metal poisoning caused by excessive accumulation of reactions, heavy metals, prevention of onset, and prevention of deterioration of symptoms. Especially in heavy metal poisoning, for example, lead poisoning, chronic nausea, vomiting, persistent or intermittent malaise, intermittent and persistent abdominal pain, bloating etc. Symptom improvement, prevention of onset, prevention of symptom deterioration, and chromium can be exemplified by improvement of symptoms such as dermatitis that may induce cancer, prevention of onset, and prevention of symptom deterioration. In addition, for example, by administering the composition of the present invention against allergic reactions such as urticaria to anisakis that sometimes occur in continuous raw meals such as sharks and squids, the causative antigens are rapidly discharged from the body. The allergic reaction can be sedated at an early stage.

  The composition of the present invention is preferably a preparation suitable for the target symptom, and specific examples include oral administration compositions such as functional foods and transdermal administration compositions such as cosmetics.

  In addition to the above essential components, oral administration compositions, specifically foods, include stabilizers, thickeners, emulsifiers, dispersants, binders, disintegrants, excipients, colorants, flavoring / flavoring agents, coatings. Preparations, sugar coatings and the like, and compositions for transdermal administration such as macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil , Cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil, hydrogenated oil, molasses, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, privet wax, lanolin, reduced lanolin, hard lanolin, jojoba oil, etc. , Waxes; hydrocarbons such as liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum, microcrystalline wax Higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid; cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl Higher alcohols such as alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, diisostearyl malate, ethylene glycol di-2-ethylhexanoate , Neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glycerin tri-2-ethylhexanoate, tri-2-ethylhexanoic acid Synthetic ester oils such as limethylolpropane, trimethylolpropane triisostearate, pentane erythritol tetra-2-ethylhexanoate; chain polysiloxanes such as dimethylpolysiloxane, methylphenylpolysiloxane, diphenylpolysiloxane; octamethylcyclo Cyclic polysiloxanes such as tetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexanesiloxane; silicone oils such as amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, fluorine-modified polysiloxane, etc. Oil agents: Anio such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, alkyl sulfate triethanolamine ether, etc. Surfactants; cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide; imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyl) Roxy disodium salt, etc.), betaine surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), and amphoteric surfactants such as acylmethyl taurine; sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquioleate, etc.) ), Glycerin fatty acids (such as glyceryl monostearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hardened castor oil derivatives, glycerin alkyl ether, POE sorbitan fatty acid ester (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE-sorbitol monolaurate, etc.), POE glycerin fatty acid esters (POE-glycerin monoisostearate, etc.), POE fatty acid Esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.), POE alkyl phenyl ethers (POE nonylphenyl ether, etc.), Pluronic types, POE / POP alkyl ethers ( POE / POP2-decyltetradecyl ether), Tetronics, POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), sucrose fatty acid ester , Nonionic surfactants such as alkyl glucoside; polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2- Polyhydric alcohols such as pentanediol, 2,4-hexanediol, 1,2-hexanediol, 1,2-octanediol; moisturizing ingredients such as sodium pyrrolidonecarboxylate, lactic acid, sodium lactate; surface treated Mica, talc, kaolin, synthetic mica, powders such as calcium carbonate, magnesium carbonate, silicic anhydride (silica), aluminum oxide, barium sulfate; surface may be treated, bengara, yellow Iron oxide, black iron oxide, acid Cobalt, ultramarine, bitumen, titanium oxide, zinc oxide inorganic pigments; surface treated pearlescent agents such as titanium mica, fish phosphorous foil, bismuth oxychloride; red raked 202, Red 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow 204, Yellow 203 Organic dyes such as Blue No. 1, Green No. 201, Purple No. 201 and Red No. 204; Organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomers; Paraaminobenzoic acid UV absorption Agent; anthranilic acid UV absorber; salicylic acid UV absorber; cinnamic acid UV absorber; benzophenone UV absorber; sugar UV absorber Agents; UV absorbers such as 2- (2′-hydroxy-5′-t-octylphenyl) benzotriazole and 4-methoxy-4′-t-butyldibenzoylmethane; lower alcohols such as ethanol and isopropanol; Vitamin A such as vitamin A or a derivative thereof, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or a derivative thereof, vitamin B12, vitamin B15 or a derivative thereof; α-tocopherol, β-tocopherol, γ -Vitamin E, such as tocopherol and vitamin E acetate, vitamin D, vitamin H, pantothenic acid, pantethine, pyrroloquinoline quinone, and the like; and an antibacterial agent such as phenoxyethanol.

  By processing the essential ingredients and optional ingredients into tablets, granules and capsules according to a conventional method, the composition of the present invention can be processed into an oral administration composition, lotion, emulsion, By processing into an essence, cream, etc., it can be processed into a composition for transdermal administration.

  Hereinafter, the present invention will be described more specifically and in detail with reference to examples.

<Production example>
(1) Weigh 100 g of the dried florets of the Rosaceae Hermanus marketed by Uchida Wakayaku Co., Ltd. under the name of Mikaika, add 2 L of 50% aqueous ethanol solution, homogenize with a homogenizer, and then at room temperature for 24 hours After soaking and removing insolubles by filtration, the filtrate was concentrated under reduced pressure, ethanol was removed and freeze-dried to obtain 21.95 g of extract (Extract 1) as amorphous. .
(2) To 5 g of extract 1, 200 ml of water and 200 ml of n-hexane were added, liquid-liquid extraction was performed, the n-hexane phase and the aqueous phase were separated, and the n-hexane phase was concentrated under reduced pressure. 049 g of extract 2 was obtained as amorphous.
(3) 200 ml of ethyl acetate was added to the aqueous phase of (2), liquid-liquid extraction was performed, the ethyl acetate phase and the aqueous phase were separated, the ethyl acetate phase was concentrated under reduced pressure, and 2.288 g of extract 3 was converted to amorphous. Got as.
(4) 200 ml of n-butanol was added to the aqueous phase of (3), liquid-liquid extraction was performed, and the n-butanol phase and the aqueous phase were separated. The n-butanol phase was concentrated under reduced pressure to obtain 0.95 g of extract 4 as amorphous. The aqueous phase was concentrated under reduced pressure to obtain 2.7 g of extract 5 as amorphous. Extract 5 was confirmed to contain 1.2% by mass of tricoumaroyl spermidine by HPLC, and was designated as “tricumaroyl spermidine fraction”.

<Production Example 2>
(1) In the same manner as in Production Example 1, 200 g of commercially available chrysanthemum flowers (dried from Asteraceae flowers) were homogenized in 4 liters of 70% water-containing ethanol, filtered and concentrated to obtain an aqueous solution of about 1 liter. Liquid-liquid distribution was carried out three times with 1 liter each of normal hexane, ethyl acetate, and normal butanol, and each was concentrated and dried. 2.6 g of chrysanthemum hexane extract, 5.3 g of chrysanthemum ethyl acetate extract, 2.6 g of chrysanthemum butanol extract 17.3 g of Kikuhanasui extract was obtained.
(2) 1.11 g of Kikuhana ethyl acetate extract was purified by medium pressure column chromatography packed with MCI-GEL CHP-20P (Mitsubishi Chemical Corporation) and fractionated into fractions 1-9. 124 milligrams of fractions 7-9, which were found to increase glutathione production (metabolic activation), were further purified by preparative high performance liquid chromatography equipped with a C-30 column to obtain 30 milligrams of tetracoumaroylspermine. . Thereby, it became clear that the active body of the metabolic activation action in a flower of Asteraceae is tetracoumaroyl spermine. Fractions 7-9 were designated as “Tetracoumaroylspermine fraction”. The tetracoumaroyl spermine fraction contained 24.2% by mass of tetracoumaroyl spermine. The ethyl chrysanthemum acetate extract contained 2.7% by mass of tetracoumaroylspermine.

<Metabolic promotion effect>
Regarding the metabolic activation effect, the combined effect of the polyamine derivative and the prosthetic / active blood crude drug extract was examined using the total amount of glutathione as an index. A human liver cancer-derived cell line HepG2 (manufactured by ATCC) was used for the test. Cells are suspended in a cell culture medium (ATCC) containing 10% fetal calf serum (GIBCO), seeded on a culture plate, and placed in a CO2 incubator (95% air, 5% carbon dioxide), 37 The cells were cultured for 24 hours under the condition of ° C.
After culturing for 24 hours, the sample was replaced with a sample-added medium in which the dry solid content of each extract was contained in the medium at a concentration of 20 μg / mL. That is, the medium cultured as described above was removed from the culture plate, and the cell culture medium (manufactured by ATCC), which was added in advance so that each extract was contained at a concentration of 20 μg / mL, was replaced with the culture plate. The cells were cultured in an incubator (95 vol% air, 5 vol% carbon dioxide) at 37 ° C for 24 hours.
After culturing for 24 hours in this manner, the amount of glutathione (total amount of glutathione) was measured using the GSH / GSSG-412 kit (manufactured by OXIS Research) according to the same instructions. That is, after removing the HepG2 cell culture medium as described above, the supernatant was washed with PBS. The washing was repeated again. The cells were collected and then frozen and thawed at −30 ° C. to elute intracellular glutathione. That is, the culture plate was centrifuged at 1000 g for 15 minutes at 20 ° C., and the supernatant was used as a measurement sample. The precipitate was used for protein quantification.
The glutathione concentration was measured according to the kit instructions. 200 μL of glutathione standard, blank, and measurement sample were placed in each cuvette, 200 μL of chromogen and 200 μL of enzyme solution included in the kit were added to each cuvette, and incubated at room temperature for 5 minutes. Thereafter, 200 μL of NADPH solution included in the kit was added to each cuvette, and the change in absorbance at 412 nm was measured for 3 minutes. The glutathione concentration was calculated from a calibration curve prepared with a glutathione standard set at the same time. The amount of protein in the cell precipitate obtained as described above was determined using a protein assay (manufactured by Bio-Rad). The amount of glutathione was expressed as the amount of glutathione per protein amount. The results are shown in Table 1 and FIG.

<Formulation example>
According to the prescription shown below, the foodstuff which is a composition of this invention was manufactured. That is, prescription component 1 was charged into a pneumomerizer, granulated while spraying 10 parts by mass of a 20% aqueous ethanol solution, blown and dried at 40 ° C. for 4 hours, then compressed into 100 mg tablets, and the food of the present invention. 1-10 were obtained.

  A food composition was produced in the same manner as in Example 4.

  A cosmetic was produced according to the following formulation. That is, the components (a), (b) and (c) were each heated to 80 ° C., added to (b) and neutralized, gradually added with emulsification with stirring, emulsified, and cooled by stirring to obtain an essence.

  In the same manner as in Example 6, the cosmetic of the present invention was produced according to the following formulation.

  The present invention can be applied to foods and cosmetics.

It is a figure which shows glutathione production activity.

Claims (6)

1) A composition containing a phenylpropenoyl polyamine derivative represented by the following general formula (1) and / or a salt thereof, and 2) an extract of a supplementary blood or a live blood crude drug.

General formula (1) (wherein R is a monoamine constituent unit, each independently a hydrogen atom or a phenylpropenoyl group in which an aromatic hydrogen atom may be substituted with a hydroxy group or a C1-4 alkyloxy group ( A propan-2-en-1-yl) group, and at least one R in the polyamine structural unit is a phenylpropenoyl (3) in which an aromatic hydrogen atom may be substituted with a hydroxy group or a C1-4 alkyloxy group -Phenylpropan-2-en-1-noyl) group, m represents an integer of 1 to 5, and n represents an integer of 2 to 5 each independently in a monoamine constituent unit. The composition according to claim 1, wherein the phenylpropenoyl polyamine derivative is tricoumaroyl spermidine or tetracoumaroyl spermine.

Trikumaroyl spermidine

Tetracoumaroylspermine The above-mentioned supplementary blood or live-blooded herbal medicines are Senkyu, Tanjin, Caquette, Motousei, Engosaku, Turmeric, Kyodo, Yakumoso, Juwishi, Taklang, Ryoshouka, Geckika, Sakubai, Shikarak, Sekishaku, Tonin, Kou, Bunkosan, Gyutsu, The wormwood is selected from the group consisting of:, Motsuyaku, Goshitsu, Ohurugyo, Lorotsu, Ryukdo, Lactocuda, Keketsu, Soboku, Kyuseishi, Goreishi, Garyobushi, Pangolin, Sweets, Shachu, Sanyoketsu, Gou and Yutan. Or the composition of 2. The extract of the supplementary blood or active blood crude drug is an extract obtained by extracting a crude drug with water, alcohol or a mixture thereof, or a fraction purified product of the extract, according to any one of claims 1 to 3. The composition according to claim 1. The composition according to any one of claims 1 to 4, which is a composition for metabolic activation. The said composition is foodstuffs or cosmetics, The composition in any one of Claims 1-5 characterized by the above-mentioned.

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