WO2006061915A1 - Skin remedy composition - Google Patents

Skin remedy composition Download PDF

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Publication number
WO2006061915A1
WO2006061915A1 PCT/JP2004/018777 JP2004018777W WO2006061915A1 WO 2006061915 A1 WO2006061915 A1 WO 2006061915A1 JP 2004018777 W JP2004018777 W JP 2004018777W WO 2006061915 A1 WO2006061915 A1 WO 2006061915A1
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WO
WIPO (PCT)
Prior art keywords
skin
weight
proanthocyanidins
pine bark
component
Prior art date
Application number
PCT/JP2004/018777
Other languages
French (fr)
Japanese (ja)
Inventor
Kinya Takagaki
Takeshi Mitsui
Original Assignee
Toyo Shinyaku Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Toyo Shinyaku Co., Ltd. filed Critical Toyo Shinyaku Co., Ltd.
Priority to PCT/JP2004/018777 priority Critical patent/WO2006061915A1/en
Publication of WO2006061915A1 publication Critical patent/WO2006061915A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/3533,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • A61K31/375Ascorbic acid, i.e. vitamin C; Salts thereof

Definitions

  • the present invention relates to a skin improvement composition.
  • Collagen is the main component of skin or blood vessels, and is a flexible fibrous protein that occupies 25-30% of the human body. If the production of collagen is normal, it can maintain tension and smooth skin. Furthermore, in blood vessels, elastic blood vessels are formed, and arteriosclerosis is unlikely to occur. 'However, collagen production ability (synthesis ability) decreases due to aging, uneven nutrition due to unbalanced diets, etc., and this decrease in collagen production causes skin itchiness and sagging.
  • the objective of this invention is providing the skin improvement composition which has the outstanding skin quality improvement effect.
  • the present inventors surprisingly have a pine bark extract and a collagen production promoting effect. It was found that the combination with an amino acid exerted an excellent collagen production enhancing effect both in the oral administration and the transdermal administration, and as a result, the skin quality was improved, and the present invention was completed. It was.
  • the skin improvement and synthesis product of the present invention contains proanthocyanidins and amino acids having an effect of promoting collagen production.
  • ascorbic acid or a derivative thereof is further contained.
  • the proanthocyanin is derived from pine bark.
  • the skin improvement composition of the present invention contains proanthocyanidins (hereinafter sometimes referred to as “A component”) and amino acids having an effect of promoting collagen production (hereinafter sometimes referred to as “amino acid component” and “B component”). Preferably, it may further contain ascorbic acid or a derivative thereof (hereinafter sometimes referred to as “C component”).
  • a component proanthocyanidins
  • amino acid component amino acids having an effect of promoting collagen production
  • ascorbic acid or a derivative thereof hereinafter sometimes referred to as “C component”.
  • This skin improvement composition may contain other components as required.
  • each component will be described.
  • proanthocyanidins are those having a degree of polymerization of flavan 1-3-ol and Z or flavan 1 3,4-diol as a structural unit of 2 or more.
  • a condensation polymer having a low polymerization degree particularly a condensation polymer having a polymerization degree of 2 to 4 (2 to 4 mer) is preferably used.
  • a polycondensation polymer having a degree of polymerization of 2 to 4 is referred to as oligomeric proanthocyanidin (hereinafter OPC).
  • OPC oligomeric proanthocyanidin
  • Allo / intanidin is a kind of polyphenols, a powerful anti-acid substance produced by plants, concentrated in plant leaves, bark, fruit peel or seed parts.
  • Proanthocyanin especially OPC, specifically, the bark of plants such as pine, persimmon, and yam; grapes, blueberries, strawberries, apogado, green tea, berries or seeds of barley; wheat; soybeans; black soybeans Cocoa; beans; tochi nut shells; peanut skins; Also in West African cola nuts, Peruvian Latania roots, Japanese green tea,
  • OPC is included. OPC is a substance that cannot be produced in the human body.
  • proanthocyanidins with a high OPC content or proanthocyanidins with a high OPC content compared to the case of using proanthocyanidins with a high degree of polymerization (low OPC content).
  • OPC can contribute not only to a direct skin quality improvement effect but also to an indirect skin quality improvement effect.
  • proanthocyanidins used in the skin improving thread and adult product of the present invention food ingredients such as the above-mentioned bark, fruit or seed meal, or extracts thereof can be used.
  • an extract derived from pine bark is preferable to use.
  • pine bark is rich in OPC, and is therefore preferably used as a raw material for proanthocyanidins.
  • an example of using pine bark rich in OPC as a raw material plant will be described as a method for preparing an extract containing puffer anthocyanin as a main component.
  • Pine pine bark extracts include Pinus Martima, larch, black pine, waka pine, himekomatsu, pine pine, Korean pine, pine, Ryuyuki pine, luck pine, pine pine, white pine, and Quebec in Canada.
  • An extract of a bark of a plant belonging to the order of pine is preferably used. Above all, the bark extract of French coastal pine (Pinus Martima) is preferred.
  • French pine is a marine pine that grows on the Atlantic coast of southern France. This French coastal pine bark contains proanthocyanidin, organic acids, and other physiologically active ingredients, and removes the active oxygen from the main ingredients, the proanthocyanidins of the flavonoids. It is known to have a strong antioxidant effect.
  • the pine bark extract is obtained by extracting the pine bark with water or an organic solvent.
  • water it is preferable to use warm water or hot water.
  • a salt such as sodium chloride to these waters.
  • the organic solvent used for extraction an organic solvent that is acceptable for the production of foods or drugs is used.
  • aqueous organic solvents may be used alone or in combination.
  • hot water, hydrous ethanol, and hydrous propylene glycol are preferably used.
  • the method for extracting proanthocyanidins from pine bark is not particularly limited, For example, a warm extraction method or a supercritical fluid extraction method is used.
  • Supercritical fluid extraction is a method that uses a supercritical fluid, which is a fluid that exceeds the critical point (critical temperature, critical pressure) of a substance's gas-liquid.
  • a supercritical fluid which is a fluid that exceeds the critical point (critical temperature, critical pressure) of a substance's gas-liquid.
  • the supercritical fluid carbon dioxide, ethylene, propane, nitrous oxide (laughing gas) and the like are used, and carbon dioxide is preferably used.
  • the supercritical fluid extraction method performs an extraction process of extracting a target component with a supercritical fluid and a separation process of separating the target component and the supercritical fluid.
  • the separation step any of extraction separation by pressure change, extraction separation by temperature change, or extraction separation using an adsorbent / absorbent may be performed.
  • supercritical fluid extraction may be performed by an entrainer addition method.
  • ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, or ketones are added to a supercritical fluid.
  • the solubility of the target extract such as OPC and catechins (described later) in the extraction solvent is dramatically increased.
  • it is a method for enhancing the selectivity of separation, and a method for efficiently obtaining a pine bark extract.
  • the supercritical fluid extraction method can be operated at a relatively low temperature, so it can be applied to substances that are altered and decomposed at high temperatures; the advantage is that the extraction fluid does not remain; and the recycling of the solvent is possible. There is an advantage that the solvent process can be omitted and the process becomes simple.
  • Extraction from pine bark may be performed by a liquid carbon dioxide batch method, a liquid carbon dioxide reflux method, a supercritical carbon dioxide reflux method, or the like in addition to the above method.
  • a plurality of extraction methods may be combined. It is edible to obtain pine bark extracts with various compositions by combining multiple extraction methods.
  • the pine bark extract obtained by the above extraction may be purified for the purpose of increasing the proanthocyanidin content.
  • a solvent such as ethyl acetate is usually used.
  • a method that does not use a solvent is required to facilitate the application to skin cosmetics and quasi drugs as external preparations.
  • it is preferable to purify by ultrafiltration or a column method or a batch method using an adsorbent biocarrier such as Diaion HP — 20, Cefadex-LH 20 or chitin.
  • the pine bark extract containing proanthocyanidin as a main component is specifically prepared by the following method, but this is an example and is not limited to this method.
  • the precipitate is dissolved in 100 ml of ethyl acetate, and then added to 1 L of black mouth form again for precipitation, and then a washing step is repeated twice.
  • a washing step is repeated twice.
  • the extract derived from the raw material plant such as pine bark preferably contains 40% by weight or more of proanthocyanidins.
  • this source plant derived preferably contains 20% by weight or more of OPC, more preferably 30% by weight or more.
  • a pine bark extract is preferably used as a raw material containing proanthocyanidins in a high proportion.
  • plant extracts such as the above-mentioned pine bark extract further contain catechins together with proanthocyanidins, particularly ⁇ PC.
  • Strength Tekins is a general term for polyhydroxyflavan 1-3-ol.
  • (+)-catechin referred to as catechin in the narrow sense
  • (1) one-catecatechin, (+)-gallocatechin, (_)-epigalocatechin, epigalocatechin gallate, epicatechin gallate Affzerekin is known.
  • the catechins are preferably contained in the raw material plant extract in an amount of 5% by weight or more. More preferably, the extract contains 20% by weight or more of OPC and 5% by weight or more of catechins. For example, if the extract contains less than 5% by weight of strength techins, the strength may be adjusted so that the final content is 5% by weight or more. It is most preferable to use a pine bark extract containing 20% by weight or more of OPC and 5% by weight or more of catechins.
  • the content of proanthocyanidins contained in the skin improvement and composition of the present invention is not particularly limited. It is preferably contained in the skin improvement composition so that the daily intake of proanthocyanidins is preferably 5 mg to 100 mg, more preferably 10 mg to 50 O mg.
  • the skin improvement composition When used as an external preparation, it is locally administered.
  • the din is preferably contained in an amount of 0.001 to 10% by weight, more preferably 0.01 to 5% by weight. If the amount is less than 0. 5% by weight, the skin quality improving action is not sufficiently exerted, and if it exceeds 10% by weight, formulation may be difficult.
  • Proanthocyanidins used in the present invention have an effect of enhancing collagen production, and therefore can improve skin quality.
  • the amino acid having an effect of promoting collagen production contained in the skin improvement composition of the present invention is an important amino acid that is a constituent component of collagen, and preferably from proline, glycine, arginine, and alanine. And at least one amino acid selected from the group consisting of:
  • These amino acids are the components of collagen that contain an average of 2% proline, an average of 21% glycine, an average of 8.1% of alanine, and an average of 6.9% of arginine. Contained. These are amino acids that are normally synthesized in vivo but are difficult to ingest sufficient amounts from a normal diet.
  • the above amino acids have better absorption efficiency in both transdermal administration and oral administration than collagen, so they are more effectively absorbed and easily converted into collagen in the body than in the case of administering collagen itself. Is done. Therefore, the above-mentioned amino acid can have a higher skin quality improving effect when combined with proanthocyanidins than collagen.
  • Proline is particularly important for improving skin because the collagen that makes up the skin is an essential amino acid for the helix structure. That is, collagen is formed by three polypeptide chains having a helix structure.
  • proline in the collagen is reduced using vitamin C as a coenzyme. This is because it becomes hydroxyproline, and the three polypeptide chains form a hydrogen bond with the hydroxyl group of the hydroxyproline to form a helix.
  • the amino acid is preferably contained in the skin improvement composition of the present invention so that the daily intake is 50 mg to 20 g, preferably 100 mg to 10 g.
  • the amount of amino acid may be appropriately adjusted so that it can be administered topically.
  • 0.001 to 5% by weight in the skin improvement composition is more preferable.
  • Ascorbic acid (vitamin C) and its derivatives are important for collagen synthesis.
  • the collagen production enhancing effect can be further enhanced. This effect is particularly effective when the composition of the present invention is orally administered. If you transdermal administration, in order to facilitate the percutaneous absorption of Asukorubin acid, it is not preferable to use a Asukorubin acid lipophile 'I 1 production is enhanced in palmitic Sana Sukorubiru.
  • Ascorbic acid and its derivatives may be contained in the skin-improving composition preferably in an amount of 0.0001 to 30% by weight, more preferably 0.001 to 10% by weight.
  • the skin improvement composition of the present invention may contain various components in addition to the above components depending on the application.
  • ingredients that can be added as normal foods and pharmaceuticals antioxidants, excipients, fillers, binders, thickeners, emulsifiers, lubricants, wetting agents, suspending agents, coloring agents, flavoring agents, Nutritional ingredients, food additives, etc.
  • ingredients normally used as skin preparations for cosmetics, pharmaceuticals, etc. whitening agents, moisturizers, antioxidants, oily ingredients, surfactants, thickeners, alcohols
  • Powder components colorants, aqueous components, various skin nutrients, etc.
  • the antioxidant may be contained for the purpose of preventing rough skin due to oxidation and aging.
  • examples of such antioxidants include SOD, mannitol, carotenoids (eg, wastaxanthin), hydroquinone, ubiquinone, bilbiline, cholesterol, tryptophan, histidine, vitamin P-like substances (rutin, quercetin, hesperidin, etc.) Gallic acid, vitamins B, vitamin D or its derivatives, vitamin E, dartathione, BTH, B HA, plant extracts (eg, argon and rosemary).
  • Such an antioxidant is preferably from 0.01 to 40% by weight in the skin-improving composition. It can be contained in a ratio of / 0 .
  • the skin improvement composition When ingesting the skin improvement composition as a food, medicine, etc., preferably at a rate of 0.01% to 20% by weight, more preferably 0.01% to 10% by weight.
  • it may be contained preferably in a proportion of 0.01 to 40% by weight, more preferably 0.01 to 20% by weight.
  • Nutritional ingredients include, for example, royal jelly, vitamins, protein, strong rumum-containing materials (eg eggshell calcium), lecithin, chlorella powder, ashtaba powder, and moroheiya powder.
  • food additives include stevia powder, matcha powder, lemon powder, honey, reduced maltose, lactose, sugar solution, and seasonings.
  • the skin improvement composition of the present invention contains proanthocyanidins and amino acids having an effect of promoting collagen production, and the ratio thereof is arbitrary.
  • the amino acid is preferably contained in an amount of 50 to 500 parts by weight, more preferably 10 to 500 parts by weight with respect to 100 parts by weight of proanthocyanidins. Can do.
  • the skin improvement composition of the present invention may further contain ascorbic acid or a derivative thereof and other components in addition to the above essential components.
  • This skin improvement composition can be prepared in various forms as, for example, foods, pharmaceuticals, quasi-drugs, cosmetics, etc. for the purpose of obtaining a skin quality improvement effect.
  • the skin improvement composition of the present invention when orally ingested as food, pharmaceuticals, quasi drugs, etc., there is no particular limitation on the form.
  • capsules such as hard capsules and soft capsules, tablets, pills, powder (powder), granules, tea bags, bowl-like viscous liquids, liquids, etc. are used in a form commonly used by those skilled in the art .
  • these may be taken as they are, or may be taken by dissolving in water, hot water, milk, etc., or may be taken after leaching the ingredients.
  • the skin improvement composition of the present invention is applied to the skin as a quasi-drug, cosmetics, etc.
  • these forms are not particularly limited, and are for ointments, creams, emulsions, mouth lotions, packs, poultices, baths. Any form may be used as long as it is a form used in conventional skin external preparations such as a preparation.
  • mouthwash such as mouthwash, toothpaste, eye drops, etc. J3 may be in a form suitable for application to the mucous membrane in the air or eyes, and these can obtain mucosal strengthening and protective action by the same action .
  • the skin improvement composition of the present invention contains a proanthocyanin and an amino acid having an effect of promoting collagen production, and takes in foods, pharmaceuticals, etc. comprising the composition, or applies cosmetics or the like to the skin. Increases the amount and exhibits an excellent skin quality improvement effect. This effect can be obtained even when the ability to produce collagen is reduced.
  • the composition of the present invention can be used as a food, a pharmaceutical product, a quasi-drug, a cosmetic product, etc. excellent in improving skin firmness and preventing wrinkles.
  • the composition of the present invention is useful as a topical skin preparation or health food that has an effect of improving skin quality (beauty effect) indirectly because proanthocyanidins, especially OPC, have an excellent anti-stress effect. It is.
  • Purified water (7.2 L) was added to 900 g of pine bark, and the mixture was broken with a blender (Waring Blender) and heated at 100 ° C. for 10 minutes. Then, it was immediately filtered to obtain a filtrate. The residue after filtration was washed with 1.8 L of purified water, and the filtrate and the washing solution were combined to obtain 9 L of a crude pine bark extract.
  • the crude extract was allowed to cool to 25 ° C., sodium chloride was added to 100% saturated concentration and stirred well, and then allowed to stand at 4 ° C. for 24 hours. After standing, this solution was filtered to obtain a filtrate. 1 L of the above filtrate was further purified by the steps shown below. First, the filtrate was passed through a 30 x 300 mm force ram filled with 100 ml of an aromatic synthetic resin swollen with water (Diaion HP—20: manufactured by Mitsubishi Chemical Corporation). And further washed with 1 L of purified water. Subsequently, the column was eluted with 15% (V / V) ethanol mixed solvent in ethanol to obtain 200 mL of purified pine bark extract.
  • the purified pine bark extract obtained was freeze-dried and powdered. Repeat this procedure to dry the purified pine bark extract from 9 L pine bark hot water extract. A dry powder of 7.21 g was obtained. Dry powder of the purified pine bark extract, a Puroanto Shianijin 40 wt% (20 wt 0/0 as OPC) contained.
  • proanthocyanidins were administered dermally (application) or orally (orally ingested) to test guinea pigs whose skin collagen content had been reduced in advance. After the administration, hydroxyproline (hyp amount) specifically present in collagen constituting the skin was measured.
  • test guinea pigs Of the five groups of test guinea pigs, three groups of test guinea pigs (groups a to c) were used. First, the hair of the site of the three groups of guinea pigs to be administered transdermally was removed using a clipper. The aqueous solution to a dry powder of the obtained pine bark extract in Preparation containing 0.3 by weight%, a group of guinea pigs site hair was removed the (a group) 5 00 ⁇ L / 5 00 cm 2 And then dried with cold air. This coating and drying operation was performed once a day for 2 weeks. During the application period, mol Kis were given low vitamin C diet ad libitum.
  • the amount of skin hypops was measured as follows. The skin was removed from the guinea pig and dried overnight at 60 ° C. This dried product was pulverized, and 5 Omg of the powder frame was added to 5 mL of hydrochloric acid (6M), maintained at 110 ° C using a heating block, and hydrolyzed for 24 hours. Hy pi in this hydrolyzate was measured by the chloramine T method. The results are shown in Table 1. The higher the amount of hypo, the greater the amount of collagen in the skin, indicating that the skin is improved.
  • test guinea pigs (groups b and c) from which the remaining two groups of hair had been removed contained an aqueous solution containing 0.3% by weight of grape seed extract (Kikkoman Corporation) containing 38% by weight of proanthocyanidin. Purified water was applied to each skin, and the amount of hypo in the skin was measured in the same manner as described above. The results are shown in Table 1.
  • test guinea pigs Of the remaining two groups of test guinea pigs (groups d and e), one group of test guinea pigs (group d) was mixed with 0.3% by weight of the dry powder of the pine bark extract obtained in the above production example. The low-vitamin C diet contained was freely given for 2 weeks. After the intake period, the amount of Hyp was measured as described above. The remaining one group of test guinea pigs (e group) contains a low vitamin C diet containing 0.3% by weight of pudo seed extract (Kikko Isman Co., Ltd.) containing 38% by weight of proanthocyanidins. Ingested in the same manner and measured the amount of Hyp. These results are shown in Table 1.
  • the Hyp amount increased, and the Hyp amount recovered to almost the same level as the healthy subject (control). I understand. In particular, it can be seen that the pine bark extract has an excellent skin improvement effect compared to other plant extracts.
  • the dry powder (component A) and proline (component B) of the pine bark extract obtained in the above production example were mixed with the low vitamin C feed in the proportions shown in Table 2 to produce feed 1.
  • Examples 2 to 4 Preparation of feed 2 to 4
  • alanine, glycine, and arginine were used as other B components instead of proline (B component), and mixed in the proportions shown in Table 2, respectively. 2-4 were produced.
  • Example 2 In addition to the composition of Example 1, A feed 5 was produced in the same manner as in Example 1 except that ascorbic acid was mixed as a component at a ratio shown in Table 2.
  • Feeds were produced by mixing the ingredients listed in Table 2, and these were designated as feeds 6 and 7.
  • Ingredients are in weight percent. Ingredients are low vitamin c feed.
  • a lotion 2 was produced in the same manner as in Example 14 except that the dry powder of pine bark extract was not dissolved in the base at the ratio shown in Table 4.
  • the number is the number of people who answered yes
  • the group ingesting tablet 1 of Example 13 has an excellent skin improvement effect compared to the group ingesting tablet 2 of Comparative Example 5. It can be seen that the group to which the lotion 1 of Example 14 was applied had an excellent skin improvement effect as compared to the group to which the lotion 2 of Comparative Example 6 was applied. From the above, the skin improvement composition of the present invention has an excellent skin improvement effect in both oral administration and transdermal administration. It turns out that a fruit is obtained.
  • a beverage was prepared by mixing the dry powder of the pine bark extract obtained in Production Example and the following ingredients:
  • the dry powder of the pine bark extract obtained in the production example and the following components were uniformly stirred and mixed to obtain a gel-like product, which was then applied to a polyester film (50 / im thickness) with a gel thickness l After forming the film to a thickness of mm, it was bonded to a polyester nonwoven fabric (elongation 50%) and heated at 50 ° C. for 24 hours to obtain a sheet-like water-containing pack agent.
  • This pack is expected to be extremely effective because it can be transdermally administered in large amounts locally on proanthocyanidins and amino acids:
  • an excellent skin improvement effect can be obtained by ingesting or applying a skin improvement thread and composition containing p-Panthocyanidin and an amino acid having a collagen production promoting effect.
  • the skin improvement composition of the present invention can be effectively used for foods, pharmaceuticals, quasi drugs, cosmetics and the like.

Abstract

A skin remedy composition comprising proanthocyanidin and an amino acid capable of exerting a collagen production spurring effect. The skin remedy composition exerts an excellent collagen production enhancing effect to thereby improve the skin quality.

Description

明 細 書 皮膚改善組成物 技術分野  Description Skin Improvement Composition Technical Field
本発明は、 皮膚改善組成物に関する。 背景技術  The present invention relates to a skin improvement composition. Background art
コラーゲンは皮膚あるいは血管の主成分であり、 ヒトの体内の 25〜3 0%を占める弾力性のある繊維状のタンパク質である。 コラーゲンの産生が 正常であれば、 張りがあり、 かつ滑らかな肌を保つことができる。 さらに血 管においては、 弾力のある血管が形成され、 動脈硬化などが起こりにくい。' しかしながら、 コラーゲンの産生能力 (合成能力) は、 老化、 偏食による 栄養摂取の偏りなどによって低下し、 このコラーゲン産生量の減少が、 皮膚 のシヮやたるみを引き起こす。  Collagen is the main component of skin or blood vessels, and is a flexible fibrous protein that occupies 25-30% of the human body. If the production of collagen is normal, it can maintain tension and smooth skin. Furthermore, in blood vessels, elastic blood vessels are formed, and arteriosclerosis is unlikely to occur. 'However, collagen production ability (synthesis ability) decreases due to aging, uneven nutrition due to unbalanced diets, etc., and this decrease in collagen production causes skin itchiness and sagging.
このような背景の下、 コラーゲンの産生増強作用を有する食品おょぴィ匕粧 品が提案され、 肌質を改善する試みがなされている (例えば、 特表昭 60— 500955号公報、 特開平 7— 2699号公報、 特開平 7— 285846 号公報、 特開平 11一 315007号公報、 およぴ特開 2000— 1914 98号公報) 。 しかし、 現代人は、 栄養パランスの偏った食事を摂取してい ることが多いため、 これらの食品およぴ化粧品を経口投与または経皮投与 (塗布) により摂取しても、 その効果は十分ではない。 発明の開示  Under such circumstances, food opi cosmetics having an action of enhancing collagen production have been proposed, and attempts have been made to improve the skin quality (for example, JP 60-500955, JP 7-2699, JP-A-7-285846, JP-A-11-315007, and JP2000-191498). However, because modern people often eat meals with a biased nutritional balance, even if these foods and cosmetics are taken orally or transdermally (application), the effect is not sufficient. Absent. Disclosure of the invention
本発明の目的は、 優れた肌質改善効果を有する皮膚改善組成物を提供する ことにある。 本発明者らは、 肌の状態の改善、 特に肌のコラーゲン量を改善する組成物 について、 鋭意検討を行った結果、 驚くべきことに、 松樹皮抽出物と、 コラ 一ゲン産生促進効果を有するアミノ酸との組み合わせが、 経口投与およぴ経 皮投与のいずれにおいても、 優れたコラーゲンの産生増強作用を発揮し、 そ の結果、 肌質を改善することを見出して本発明を完成するに至った。 The objective of this invention is providing the skin improvement composition which has the outstanding skin quality improvement effect. As a result of intensive investigations on a composition that improves skin condition, particularly the amount of collagen in the skin, the present inventors surprisingly have a pine bark extract and a collagen production promoting effect. It was found that the combination with an amino acid exerted an excellent collagen production enhancing effect both in the oral administration and the transdermal administration, and as a result, the skin quality was improved, and the present invention was completed. It was.
本発明の皮膚改善,袓成物は、 プロアントシァニジンと、 コラーゲン産生促 進効果を有するアミノ酸とを含有する。  The skin improvement and synthesis product of the present invention contains proanthocyanidins and amino acids having an effect of promoting collagen production.
好ましい実施態様においては、 さらに、 ァスコルビン酸またはその誘導体 を含有する。  In a preferred embodiment, ascorbic acid or a derivative thereof is further contained.
好ましい実施態様においては、 上記プロアントシァ-ジンは、 松樹皮由来 である。 発明を実施するための最良の形態  In a preferred embodiment, the proanthocyanin is derived from pine bark. BEST MODE FOR CARRYING OUT THE INVENTION
以下、 本発明の皮膚改善組成物について説明する。 なお、 以下に説明する 構成は、 本発明を限定するものでなく、 本発明の趣旨の範囲内で種々改変す ることができる。  Hereinafter, the skin improvement composition of the present invention will be described. The configurations described below do not limit the present invention, and various modifications can be made within the scope of the gist of the present invention.
本発明の皮膚改善組成物は、 プロアントシァニジン (以下、 A成分という 場合がある) と、 コラーゲン産生促進効果を有するアミノ酸 (以下、 ァミノ 酸成分、 B成分などという場合がある) とを含有し、 好ましくは、 さらにァ スコルビン酸またはその誘導体 (以下、 C成分という場合がある) を含有し 得る。 この皮膚改善組成物は、 必要に応じて、 その他の成分を含有し得る。 以下、 各成分について説明する。  The skin improvement composition of the present invention contains proanthocyanidins (hereinafter sometimes referred to as “A component”) and amino acids having an effect of promoting collagen production (hereinafter sometimes referred to as “amino acid component” and “B component”). Preferably, it may further contain ascorbic acid or a derivative thereof (hereinafter sometimes referred to as “C component”). This skin improvement composition may contain other components as required. Hereinafter, each component will be described.
( 1 ) プロアントシァニジン (A成分) (1) Proanthocyanidins (component A)
本明細書において、 プロアントシァニジンとは、 フラバン一 3—オールお よび Zまたはフラバン一 3 , 4—ジオールを構成単位とする重合度が 2以上 の縮重合体からなる化合物群をいう。 In this specification, proanthocyanidins are those having a degree of polymerization of flavan 1-3-ol and Z or flavan 1 3,4-diol as a structural unit of 2 or more. The compound group which consists of a polycondensation polymer of said.
このプロアントシァニジンとしては、 重合度の低い縮重合体、 特に重合度 が 2〜4の縮重合体 (2〜4量体) が好ましく用いられる。 この重合度が 2 〜 4の縮重合体を、 本明細書ではオリゴメリック 'プロアントシァニジン (oligomeric proanthocyanidin:以下、 O P Cといつ) とレヽつ。 ァロ/ン トシァニジンは、 ポリフエノール類の一種で、 植物が作り出す強力な抗酸ィ匕 物質であり、 植物の葉、 樹皮、 果物の皮もしくは種の部分に集中的に含まれ ている。 プロアントシァ-ジン、 特に O P Cは、 具体的には、 松、 樫、 山祧 などの植物の樹皮;ブドウ、 ブルーベリー、 イチゴ、 アポガド、 ニセァカシ ァ、 コケモモの果実もしくは種子;大麦;小麦;大豆;黒大豆;カカオ;小 豆; トチの実の殻; ピーナッツの薄皮;ィチヨゥ葉などに含まれている。 ま た、 西アフリカのコーラナッツ、 ペルーのラタニアの根、 日本の緑茶にも、 As this proanthocyanidin, a condensation polymer having a low polymerization degree, particularly a condensation polymer having a polymerization degree of 2 to 4 (2 to 4 mer) is preferably used. In this specification, a polycondensation polymer having a degree of polymerization of 2 to 4 is referred to as oligomeric proanthocyanidin (hereinafter OPC). Allo / intanidin is a kind of polyphenols, a powerful anti-acid substance produced by plants, concentrated in plant leaves, bark, fruit peel or seed parts. Proanthocyanin, especially OPC, specifically, the bark of plants such as pine, persimmon, and yam; grapes, blueberries, strawberries, apogado, green tea, berries or seeds of barley; wheat; soybeans; black soybeans Cocoa; beans; tochi nut shells; peanut skins; Also in West African cola nuts, Peruvian Latania roots, Japanese green tea,
O P Cが含まれることが知られている。 O P Cは、 ヒトの体内では、 生成す ることのできない物質である。 It is known that OPC is included. OPC is a substance that cannot be produced in the human body.
特に、 O P C含有量が高いプロアントシァ-ジンまたは O P C含有量が高 いプロアントシァニジンを含む抽出物を用いると、 重合度の高いプロアント シァニジン (O P C含有量が少ないもの) を用いた場合と対比して、 優れた 抗酸化作用のみならず、 高い抗ストレス効果が得られる。 ストレスが溜まる と、 肌荒れなどが生じることが知られており、 ストレスを抑制することは、 肌荒れなどの防止に有益である。 O P Cは、 直接的な肌質改善効果のみなら ず、 このように間接的な肌質改善効果にも寄与し得る。  In particular, the use of proanthocyanidins with a high OPC content or proanthocyanidins with a high OPC content compared to the case of using proanthocyanidins with a high degree of polymerization (low OPC content). As a result, not only an excellent antioxidant effect but also a high antistress effect can be obtained. It is known that when stress accumulates, rough skin occurs, and suppressing stress is beneficial in preventing rough skin. OPC can contribute not only to a direct skin quality improvement effect but also to an indirect skin quality improvement effect.
本発明の皮膚改善糸且成物に用いられるプロアントシァニジンとしては、 上 記の樹皮、 果実もしくは種子の粉碎物、 またはこれらの抽出物のような食品 原料を使用することができる。 特に、 松樹皮由来の抽出物を用いることが好 ましい。 上記プロアントシァニジンを含む植物のうち、 松樹皮が O P Cを豊 富に含むため、 プロアントシァニジンの原料として好ましく用いられる。 以下、 O P Cを豊富に含む松樹皮を原料植物として用いた例に挙げて、 プ 口アントシァュジンを主成分とする抽出物の調製方法を説明する。 As the proanthocyanidins used in the skin improving thread and adult product of the present invention, food ingredients such as the above-mentioned bark, fruit or seed meal, or extracts thereof can be used. In particular, it is preferable to use an extract derived from pine bark. Among the plants containing proanthocyanidins, pine bark is rich in OPC, and is therefore preferably used as a raw material for proanthocyanidins. Hereinafter, an example of using pine bark rich in OPC as a raw material plant will be described as a method for preparing an extract containing puffer anthocyanin as a main component.
松榭皮抽出物としては、 フランス海岸松 (Pinus Martima) 、 カラマツ、 クロマツ、 ァカマツ、 ヒメコマツ、 ゴヨウマツ、 チョウセンマツ、 ハイマツ、 リユウキユウマツ、 ゥックシマツ、 ダイォゥマツ、 シロマツ、 カナダのケべ ック地方のァネダなどのマツ目に属する植物の樹皮の抽出物が好ましく用い られる。 中でも、 フランス海岸松 (Pinus Martima) の樹皮抽出物が好まし い。  Pine pine bark extracts include Pinus Martima, larch, black pine, waka pine, himekomatsu, pine pine, Korean pine, pine, Ryuyuki pine, luck pine, pine pine, white pine, and Quebec in Canada. An extract of a bark of a plant belonging to the order of pine is preferably used. Above all, the bark extract of French coastal pine (Pinus Martima) is preferred.
フランス?毎岸松は、 南仏の大西洋沿岸の一部に生育している海洋性松をい う。 このフランス海岸松の樹皮は、 プロアントシァ-ジン (proanthocyanid in) 、 有機酸、 ならびにその他の生理活性成分などを含有し、 その主要成分 であるフラポノィド類のプロアントシァニジンに、 活个生酸素を除去する強い 抗酸化作用があることが知られている。  French pine is a marine pine that grows on the Atlantic coast of southern France. This French coastal pine bark contains proanthocyanidin, organic acids, and other physiologically active ingredients, and removes the active oxygen from the main ingredients, the proanthocyanidins of the flavonoids. It is known to have a strong antioxidant effect.
松樹皮抽出物は、 上記の松樹皮を水または有機溶媒で抽出して得られる。 水を用いる場合には、 温水または熱水を用いることが好ましい。 これらの水 には、 抽出効率を向上させる点から、 塩ィ匕ナトリウムなどの塩を添加するこ とが好ましい。 抽出に用いる有機溶媒としては、 食品あるいは薬剤の製造に 許容される有機溶媒が用いられ、 例えば、 メタノール、 エタノール、 1ープ ロパノール、 2—プロパノール、 1—ブタノール、 2—プタノール、 ァセト ン、 へキサン、 シク口へキサン、 プロピレングリコール、 含水エタノール、 含水プロピレングリコール、 メチルェチルケトン、 グリセリン、 酢酸メチル、 酢酸ェチル、 ジェチルエーテル、 ジクロロメタン、 食用油脂、 および 1, 1 , 1 , 2—テトラフルォロェタンが挙げられる。 これらの水おょぴ有機溶媒は 単独で用いてもよいし、 組合わせて用いてもよい。 特に、 熱水、 含水エタノ ール、 およぴ含水プロピレングリコールが好ましく用いられる。  The pine bark extract is obtained by extracting the pine bark with water or an organic solvent. When water is used, it is preferable to use warm water or hot water. In order to improve the extraction efficiency, it is preferable to add a salt such as sodium chloride to these waters. As the organic solvent used for extraction, an organic solvent that is acceptable for the production of foods or drugs is used. For example, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, acetone, Hexane, cyclohexane, propylene glycol, water-containing ethanol, water-containing propylene glycol, methyl ethyl ketone, glycerin, methyl acetate, ethyl acetate, jetyl ether, dichloromethane, edible oil and fat, and 1, 1, 1, 2-tetrafur Oroetan. These aqueous organic solvents may be used alone or in combination. In particular, hot water, hydrous ethanol, and hydrous propylene glycol are preferably used.
松樹皮からプロアントシァニジンを抽出する方法は、 特に限定されないが、 例えば、 加温抽出法、 超臨界流体抽出法などが用いられる。 The method for extracting proanthocyanidins from pine bark is not particularly limited, For example, a warm extraction method or a supercritical fluid extraction method is used.
超臨界流体抽出法は、 物質の気液の臨界点 (臨界温度、 臨界圧力) を超え た状態の流体である超臨界流体を用いて抽出を行う方法である。 超臨界流体 としては、 二酸化炭素、 エチレン、 プロパン、 亜酸化窒素 (笑気ガス) など が用いられ、 二酸化炭素が好ましく用いられる。  Supercritical fluid extraction is a method that uses a supercritical fluid, which is a fluid that exceeds the critical point (critical temperature, critical pressure) of a substance's gas-liquid. As the supercritical fluid, carbon dioxide, ethylene, propane, nitrous oxide (laughing gas) and the like are used, and carbon dioxide is preferably used.
超臨界流体抽出法は、 目的成分を超臨界流体によって抽出する抽出工程と、 目的成分と超臨界流体とを分離する分離工程とを行う。 分離工程では、 圧力 変化による抽出分離、 温度変化による抽出分離、 または吸着剤 ·吸収剤を用 いた抽出分離のいずれを行ってもよい。  The supercritical fluid extraction method performs an extraction process of extracting a target component with a supercritical fluid and a separation process of separating the target component and the supercritical fluid. In the separation step, any of extraction separation by pressure change, extraction separation by temperature change, or extraction separation using an adsorbent / absorbent may be performed.
また、 ェントレーナー添加法による超臨界流体抽出を行ってもよい。 この 方法は、 超臨界流体に、 例えば、 エタノール、 プロパノール、 n—へキサン、 アセトン、 トルエン、 その他の脂肪族低級アルコール類、 脂肪族炭化水素類、 芳香族炭化水素類、 またはケトン類を 2〜2 0 WZV%程度添加し、 得られ た抽出流体で超臨界流体抽出を行うことによって、 O P C、 カテキン類 (後 述) などの目的とする抽出物の抽出溶媒に対する溶解度を飛躍的に上昇させ る、 あるいは分離の選択性を増強させる方法であり、 効率的に松樹皮抽出物 を得る方法である。  Alternatively, supercritical fluid extraction may be performed by an entrainer addition method. In this method, for example, ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, or ketones are added to a supercritical fluid. By adding about 20 WZV% and performing supercritical fluid extraction with the extracted fluid, the solubility of the target extract such as OPC and catechins (described later) in the extraction solvent is dramatically increased. Alternatively, it is a method for enhancing the selectivity of separation, and a method for efficiently obtaining a pine bark extract.
超臨界流体抽出法は、 比較的低い温度で操作できるため、 高温で変質 ·分 解する物質にも適用できるという利点;抽出流体が残留しないという利点; および溶媒の循環利用が可能であり、 脱溶媒工程などが省略でき、 工程がシ ンプルになるという利点がある。  The supercritical fluid extraction method can be operated at a relatively low temperature, so it can be applied to substances that are altered and decomposed at high temperatures; the advantage is that the extraction fluid does not remain; and the recycling of the solvent is possible. There is an advantage that the solvent process can be omitted and the process becomes simple.
また、 松樹皮からの抽出は、 上記の方法以外に、 液体二酸化炭素回分法、 液体二酸化炭素還流法、 超臨界二酸化炭素還流法などにより行ってもよい。 松樹皮からの抽出は、 複数の抽出方法を組み合わせてもよい。 複数の抽出 方法を組み合わせることにより、 種々の組成の松樹皮抽出物を得ることが可 食 となる。 上記抽出により得られた松樹皮抽出物は、 プロアントシァ-ジン含有量を 増加させる目的で精製してもよい。 精製には、 通常、 酢酸ェチルなどの溶媒 が用いられるが、 安全性などの面から、 さらに、 外用剤としての皮膚化粧品 および医薬部外品への応用を容易にするため、 溶媒を使用しない方法、 例え ば、 限外濾過、 あるいはダイヤイオン H P _ 2 0、 セフアデックス一L H 2 0、 キチンなどの吸着†生担体を用いたカラム法またはバッチ法により精製す ることが好ましい。 Extraction from pine bark may be performed by a liquid carbon dioxide batch method, a liquid carbon dioxide reflux method, a supercritical carbon dioxide reflux method, or the like in addition to the above method. For extraction from pine bark, a plurality of extraction methods may be combined. It is edible to obtain pine bark extracts with various compositions by combining multiple extraction methods. The pine bark extract obtained by the above extraction may be purified for the purpose of increasing the proanthocyanidin content. For purification, a solvent such as ethyl acetate is usually used. However, from the viewpoint of safety, a method that does not use a solvent is required to facilitate the application to skin cosmetics and quasi drugs as external preparations. For example, it is preferable to purify by ultrafiltration or a column method or a batch method using an adsorbent biocarrier such as Diaion HP — 20, Cefadex-LH 20 or chitin.
本発明において、 プロアントシァニジンを主成分として含む松樹皮抽出物 は、 具体的には、 以下のような方法によりに調製されるが、 これは例示であ り、 この方法に限定されない。  In the present invention, the pine bark extract containing proanthocyanidin as a main component is specifically prepared by the following method, but this is an example and is not limited to this method.
フランス海岸松の樹皮 1 k gを、 塩ィ匕ナトリゥムの飽和溶液 3 Lに入れ、 1 0 0 °Cにて 3 0分間抽出し、 抽出液を得る (抽出工程) 。 その後、 抽出液 を濾過し、 得られる不溶物を塩化ナトリゥムの飽和溶液 5 0 0 m lで洗浄し、 洗浄液を得る (洗浄工程) 。 この抽出液と洗浄液とを合わせて、 松樹皮の粗 抽出液を得る。  1 kg of French coastal pine bark is placed in 3 L of saturated sodium chloride solution and extracted at 100 ° C for 30 minutes to obtain an extract (extraction process). Thereafter, the extract is filtered, and the resulting insoluble material is washed with 500 ml of a saturated solution of sodium chloride to obtain a washing solution (washing step). The extract and washing solution are combined to obtain a crude extract of pine bark.
次いで、 この粗抽出液に酢酸ェチル 2 5 O m lを添加して分液し、 酢酸ェ チル層を回収する工程を 5回行う。 回収した酢酸ェチル溶液を合わせて、 無 水硫酸ナトリウム 2 0 0 gに直接添加して脱水する。 その後、 この酢酸ェチ ル溶液を濾過し、 濾液を元の 5分の 1量になるまで減圧濃縮する。 濃縮され た酢酸ェチル溶液を 2 Lのクロ口ホルムに注ぎ、 攪拌して得られる沈殿物を 濾過により回収する。 その後、 この沈殿物を酢酸ェチル 1 0 0 m lに溶解し た後、 再度 1 Lのクロ口ホルムに添カ卩して沈殿させる操作を 2回繰り返す洗 浄工程を行う。 この方法により、 例えば、 O P Cを 2 0重量%以上含み、 か つ力テキン類を 5重量%以上含有する、 約 5 gの松樹皮抽出物が得られる。 上記松樹皮のような原料植物に由来する抽出物は、 4 0重量%以上のプロ アントシァニジンを含有することが好ましい。 さらに、 この原料植物由来の 抽出物中に O P Cを 2 0重量%以上含有することが好ましく、 3 0重量%以 上含有することがより好ましい。 このようにプロアントシァニジンを高い割 合で含有する原料として、 上述のように松樹皮抽出物が好ましく用いられる。 上記松樹皮抽出物などの植物抽出物には、 さらにプロアントシァェジン、 特に〇P Cとともにカテキン (catechin) 類が含まれることが好ましい。 力 テキン類とは、 ポリヒドロキシフラバン一 3—オールの総称である。 力テキ ン類としては、 (+ ) —カテキン (狭義のカテキンといわれる) 、 (一) 一 ェピカテキン、 (+ ) —ガロカテキン、 (_) ーェピガロカテキン、 ェピガ ロカテキンガレート、 ェピカテキンガレート、 ァフゼレキンなどが知られて いる。 上記松樹皮のような原料植物由来の抽出物からは、 上記の (+ ) —力 テキンの他、 ガロカテキン、 ァフゼレキン、 (+ ) —力テキンの 3—ガロイ ル誘導体、 およぴガロカテキンの 3—ガロイル誘導体が単離されている。 力 テキン類は、 単独では水溶性が乏しく、 その生理活性が低いが、 O P Cの存 在下で水溶性が増すと同時に、 活性化する性質があり、 O P Cとともに摂取 することで効果的に作用する。 Then, 25 O ml of ethyl acetate is added to the crude extract to separate the solution, and the step of recovering the ethyl acetate layer is performed 5 times. Combine the recovered ethyl acetate solution and add directly to 200 g of anhydrous sodium sulfate for dehydration. Then, the ethyl acetate solution is filtered, and the filtrate is concentrated under reduced pressure until the original volume is reduced to one-fifth. The concentrated ethyl acetate solution is poured into 2 L of chloroform and the precipitate obtained by stirring is collected by filtration. Thereafter, the precipitate is dissolved in 100 ml of ethyl acetate, and then added to 1 L of black mouth form again for precipitation, and then a washing step is repeated twice. By this method, for example, about 5 g of pine bark extract containing 20% by weight or more of OPC and 5% by weight or more of strong techins is obtained. The extract derived from the raw material plant such as pine bark preferably contains 40% by weight or more of proanthocyanidins. In addition, this source plant derived The extract preferably contains 20% by weight or more of OPC, more preferably 30% by weight or more. As described above, a pine bark extract is preferably used as a raw material containing proanthocyanidins in a high proportion. It is preferable that plant extracts such as the above-mentioned pine bark extract further contain catechins together with proanthocyanidins, particularly ○ PC. Strength Tekins is a general term for polyhydroxyflavan 1-3-ol. For example, (+)-catechin (referred to as catechin in the narrow sense), (1) one-catecatechin, (+)-gallocatechin, (_)-epigalocatechin, epigalocatechin gallate, epicatechin gallate Affzerekin is known. From the above-mentioned extracts derived from raw materials such as pine bark, in addition to the above (+) — power techin, gallocatechin, afuzerekin, (+) — 3 galloyl derivative of power techin, and 3— Galloyl derivatives have been isolated. Force Tekins alone have poor water solubility and low physiological activity, but they have the property of being activated at the same time as water solubility increases in the presence of OPC, and they act effectively when taken together with OPC.
カテキン類は、 上記原料植物抽出物中に、 5重量%以上含有されているこ とが好ましい。 より好ましくは、 該抽出物中に O P Cが 2 0重量%以上、 そ してカテキン類が 5重量%以上含有される。 例えば、 抽出物の力テキン類含 量が 5重量%未満の場合、 力テキン類を添加し、 最終的な含量が 5重量%以 上となるように調整してもよい。 O P Cを 2 0重量%以上含有し、 かつカテ キン類を 5重量%以上含有する松樹皮抽出物を用いることが最も好ましい。 本発明の皮膚改善,組成物中に含まれるプロアントシァニジンの含有量は特 に限定されない。 プロアントシァニジンの一日の摂取量が好ましくは 5 m g 〜 1 0 0 0 m g、 より好ましくは 1 0 m g 〜 5 0 O m gとなるように皮膚改 善組成物中に含有されることが好ましい。 皮膚改善組成物を外用剤として用 いる場合は、 局所的な投与となるため、 皮膚改善組成物中にプロアントシァ 二ジンを好ましくは 0 . 0 0 0 1〜1 0重量%、 より好ましくは 0 . 0 0 1 〜 5重量%含有することが好ましい。 0 . 0 0 0 5重量%未満であると、 肌 質改善作用が十分に発揮されず、 1 0重量%を超えると製剤化が困難な場合 がある。 The catechins are preferably contained in the raw material plant extract in an amount of 5% by weight or more. More preferably, the extract contains 20% by weight or more of OPC and 5% by weight or more of catechins. For example, if the extract contains less than 5% by weight of strength techins, the strength may be adjusted so that the final content is 5% by weight or more. It is most preferable to use a pine bark extract containing 20% by weight or more of OPC and 5% by weight or more of catechins. The content of proanthocyanidins contained in the skin improvement and composition of the present invention is not particularly limited. It is preferably contained in the skin improvement composition so that the daily intake of proanthocyanidins is preferably 5 mg to 100 mg, more preferably 10 mg to 50 O mg. . When the skin improvement composition is used as an external preparation, it is locally administered. The din is preferably contained in an amount of 0.001 to 10% by weight, more preferably 0.01 to 5% by weight. If the amount is less than 0. 5% by weight, the skin quality improving action is not sufficiently exerted, and if it exceeds 10% by weight, formulation may be difficult.
本発明に用いられるプロアントシァ-ジン、 特に O P Cは、 コラーゲン産 生増強効果を有するため、 肌質を改善することができる。 特に、 プロアント シァニジンとして、 松樹皮由来の抽出物を用いることが、 他の植物抽出物に 比べて高!/、コラーゲン増強作用を有する点で好まし!/、。  Proanthocyanidins used in the present invention, in particular OPC, have an effect of enhancing collagen production, and therefore can improve skin quality. In particular, it is preferable to use an extract derived from pine bark as proanthocyanidin because it has a higher collagen activity than other plant extracts! /.
( 2 ) コラーゲン産生促進効果を有するアミノ酸 (B成分) (2) Amino acid (B component) that has an effect of promoting collagen production
本発明の皮膚改善組成物に含有されるコラ一ゲン産生促進効果を有するァ ミノ酸は、 コラーゲンの構成成分となる重要なアミノ酸であり、 好ましくは、 プロリン、 グリシン、 アルギニン、 およぴァラニンからなる群より選択され る少なくとも 1種のアミノ酸である。 上記アミノ酸は、 プロアントシァニジ ンと相俟って、 優れた肌質改善効果を発揮する。 これらのアミノ酸は、 例え ば、 コラーゲンの構成成分として該コラーゲン中にプロリンが平均丄 2 %、 グリシンが平均 2 1 %、 ァラニンが平均 8 . 1 %、 およびアルギニンが平均 6 . 9 %の割合で含有されている。 これらは、 通常、 生体内で合成されるが、 通常の食事から十分な量を摂取しにくいアミノ酸である。 したがって、 老化 により代謝が低下すると、 これに伴い生体内でのこれらのアミノ酸合成能力 も低下するため、 肌質を改善するためには、 特に積極的に摂取する必要があ る。 なお、 上記アミノ酸は、 コラーゲンに比べて、 経皮投与および経口投与 のいずれにおいても吸収効率がよいため、 コラーゲン自体を投与する場合に 比べて、 効果的に吸収され、 体内で容易にコラーゲンに変換される。 したが つて、 上記アミノ酸は、 コラーゲンに比べて、 プロアントシァニジンと組み 合わせる場合にも、 より高い肌質改善効果が得られ得る。 プロリンは、 肌を構成するコラーゲンがヘリックス構造をとるために必須 なアミノ酸であるため、 皮膚改善には特に重要である。 すなわち、 コラーゲ ンは、 3本のポリペプチド鎖がヘリックス構造をとつて形成されるが、 これ は繊維芽細胞がコラーゲンペプチドを合成するに際し、 コラーゲン中のプロ リンがビタミン Cを補酵素として還元され、 ハイドロキシプロリンとなり、 該ハイドロキシプロリンの水酸基により 3本のポリべプチド鎖が水素結合を 形成して、 ヘリックスが形成されるためである。 The amino acid having an effect of promoting collagen production contained in the skin improvement composition of the present invention is an important amino acid that is a constituent component of collagen, and preferably from proline, glycine, arginine, and alanine. And at least one amino acid selected from the group consisting of: The above amino acids, together with proanthocyanidins, exhibit an excellent skin quality improving effect. These amino acids, for example, are the components of collagen that contain an average of 2% proline, an average of 21% glycine, an average of 8.1% of alanine, and an average of 6.9% of arginine. Contained. These are amino acids that are normally synthesized in vivo but are difficult to ingest sufficient amounts from a normal diet. Therefore, when metabolism decreases due to aging, the ability to synthesize these amino acids in vivo is also reduced. Therefore, in order to improve skin quality, it is necessary to ingest it particularly actively. In addition, the above amino acids have better absorption efficiency in both transdermal administration and oral administration than collagen, so they are more effectively absorbed and easily converted into collagen in the body than in the case of administering collagen itself. Is done. Therefore, the above-mentioned amino acid can have a higher skin quality improving effect when combined with proanthocyanidins than collagen. Proline is particularly important for improving skin because the collagen that makes up the skin is an essential amino acid for the helix structure. That is, collagen is formed by three polypeptide chains having a helix structure. When fibroblasts synthesize collagen peptides, proline in the collagen is reduced using vitamin C as a coenzyme. This is because it becomes hydroxyproline, and the three polypeptide chains form a hydrogen bond with the hydroxyl group of the hydroxyproline to form a helix.
上記ァミノ酸は、 本発明の皮膚改善組成物中に一日の摂取量が 50 m g〜 20 g、 好ましくは 100mg〜10 gとなるように含有されることが好ま しい。 皮膚改善組成物を外用剤とする場合は、 局所的に投与できるようアミ ノ酸の量を適宜調整すればよく、 好ましくは、 皮膚改善組成物中に 0. 00 1〜5重量%、 より好ましくは 0. 005〜3重量%の割合で含有される。  The amino acid is preferably contained in the skin improvement composition of the present invention so that the daily intake is 50 mg to 20 g, preferably 100 mg to 10 g. When the skin improvement composition is used as an external preparation, the amount of amino acid may be appropriately adjusted so that it can be administered topically. Preferably, 0.001 to 5% by weight in the skin improvement composition is more preferable. Is contained in a proportion of 0.005 to 3% by weight.
(3) ァスコルビン酸およびそれらの誘導体 (C成分) (3) Ascorbic acid and their derivatives (component C)
ァスコルビン酸 (ビタミン C) およびその誘導体は、 コラーゲン合成に重 要である。 本発明の組成物中にァスコルビン酸およびその誘導体を含有する ことによって、 コラーゲン産生増強効果をより高めることができる。 この効 果は、 本発明の組成物を経口投与する場合に特に効果的である。 経皮投与す る場合は、 ァスコルビン酸の経皮吸収を容易にするために、 パルミチン酸ァ スコルビルなどの親油' I1生が高められたァスコルビン酸を用いることが好まし い。 さらに、 経皮投与の場合は、 皮膚中のコラーゲンの酸化を防止し、 合成 を促進するという観点からも、 該組成物中に含有され得る。 ァスコルビン酸 およぴその誘導体は、 皮膚改善組成物中に好ましくは 0. 0001〜 30重 量%、 より好ましくは 0. 001重量%〜 10重量%含有し得る。 Ascorbic acid (vitamin C) and its derivatives are important for collagen synthesis. By containing ascorbic acid and its derivatives in the composition of the present invention, the collagen production enhancing effect can be further enhanced. This effect is particularly effective when the composition of the present invention is orally administered. If you transdermal administration, in order to facilitate the percutaneous absorption of Asukorubin acid, it is not preferable to use a Asukorubin acid lipophile 'I 1 production is enhanced in palmitic Sana Sukorubiru. Furthermore, in the case of transdermal administration, it can be contained in the composition from the viewpoint of preventing the oxidation of collagen in the skin and promoting synthesis. Ascorbic acid and its derivatives may be contained in the skin-improving composition preferably in an amount of 0.0001 to 30% by weight, more preferably 0.001 to 10% by weight.
(4) その他の成分 本発明の皮膚改善組成物は、 上記の成分以外に、 用途に応じて、 種々の成 分を含有し得る。 例えば、 通常の食品や医薬品として添加し得る成分 (抗酸 化剤、 賦形剤、 増量剤、 結合剤、 増粘剤、 乳化剤、 滑沢剤、 湿潤剤、 懸濁剤、 着色料、 香料、 栄養成分、 食品添加物など) ;およびィ匕粧品、 医薬品等の皮 膚外用剤として通常用いられる成分 (美白剤、 保湿剤、 抗酸化剤、 油性成分、 界面活性剤、 増粘剤、 アルコール類、 粉末成分、 色剤、 水性成分、 各種皮膚 栄養剤など) が挙げられる。 (4) Other ingredients The skin improvement composition of the present invention may contain various components in addition to the above components depending on the application. For example, ingredients that can be added as normal foods and pharmaceuticals (antioxidants, excipients, fillers, binders, thickeners, emulsifiers, lubricants, wetting agents, suspending agents, coloring agents, flavoring agents, Nutritional ingredients, food additives, etc.); and ingredients normally used as skin preparations for cosmetics, pharmaceuticals, etc. (whitening agents, moisturizers, antioxidants, oily ingredients, surfactants, thickeners, alcohols) Powder components, colorants, aqueous components, various skin nutrients, etc.).
上記成分のうち、 抗酸化剤は、 酸化による肌荒れ、 老化を防止する目的で 含有され得る。 このような抗酸化剤としては、 S O D、 マン-トール、 カロ テノィド類 (例えば、 ァスタキサンチン) 、 ハイドロキノン、 ュビキノン、 ビルビリン、 コレステロール、 トリプトファン、 ヒスチジン、 ビタミン P様 物資 (ルチン、 ケルセチン、 ヘスペリジンなど) 、 没食子酸、 ビタミン B類、 ビタミン Dまたはその誘導体、 ビタミン E、 ダルタチオン、 B T H、 B HA、 植物抽出物 (例えば、 ォゥゴンおよびローズマリー) などが挙げられる。 こ のような抗酸化剤は、 皮膚改善組成物中に好ましくは 0 . 0 0 0 1重量%〜 4 0重量。 /0の割合で含有され得る。 皮膚改善組成物を食品、 医薬品などとし て摂取する場合は、 好ましくは 0 . 0 0 1重量%〜2 0重量%、 より好まし くは 0 . 0 1重量%〜 1 0重量%の割合で含有され得、 化粧品、 医薬品など として外用する場合は、 好ましくは 0 . 0 0 0 1重量%〜4 0重量%、 より 好ましくは 0 . 0 0 1〜 2 0重量%の割合で含有され得る。 Among the above components, the antioxidant may be contained for the purpose of preventing rough skin due to oxidation and aging. Examples of such antioxidants include SOD, mannitol, carotenoids (eg, wastaxanthin), hydroquinone, ubiquinone, bilbiline, cholesterol, tryptophan, histidine, vitamin P-like substances (rutin, quercetin, hesperidin, etc.) Gallic acid, vitamins B, vitamin D or its derivatives, vitamin E, dartathione, BTH, B HA, plant extracts (eg, argon and rosemary). Such an antioxidant is preferably from 0.01 to 40% by weight in the skin-improving composition. It can be contained in a ratio of / 0 . When ingesting the skin improvement composition as a food, medicine, etc., preferably at a rate of 0.01% to 20% by weight, more preferably 0.01% to 10% by weight. In the case of external use as cosmetics, pharmaceuticals, etc., it may be contained preferably in a proportion of 0.01 to 40% by weight, more preferably 0.01 to 20% by weight.
栄養成分としては、 例えば、 ローヤルゼリー、 ビタミン、 プロテイン、 力 ルシゥム含有材料 (卵殻カルシウムなど) 、 レシチン、 クロレラ末、 ァシタ バ末、 およびモロヘイヤ末が挙げられる。 食品添加物としては、 ステビア末、 抹茶パウダー、 レモンパウダー、 はちみつ、 還元麦芽糖、 乳糖、 糖液、 調味 料などが挙げられる。 ( 5 ) 皮膚改善組成物 Nutritional ingredients include, for example, royal jelly, vitamins, protein, strong rumum-containing materials (eg eggshell calcium), lecithin, chlorella powder, ashtaba powder, and moroheiya powder. Examples of food additives include stevia powder, matcha powder, lemon powder, honey, reduced maltose, lactose, sugar solution, and seasonings. (5) Skin improvement composition
本発明の皮膚改善組成物は、 プロアントシァニジンと、 コラーゲン産生促 進効果を有するアミノ酸とを含有し、 その割合は任意である。 好ましくは、 プロアントシァニジン 1 0 0重量部に対して、 上記アミノ酸を好ましくは、 5 0〜5 0 0 0重量部、 より好ましくは、 1 0 0〜5 0 0 0重量部の割合で 含有し得る。  The skin improvement composition of the present invention contains proanthocyanidins and amino acids having an effect of promoting collagen production, and the ratio thereof is arbitrary. Preferably, the amino acid is preferably contained in an amount of 50 to 500 parts by weight, more preferably 10 to 500 parts by weight with respect to 100 parts by weight of proanthocyanidins. Can do.
本発明の皮膚改善組成物は、 上記の必須成分以外に、 さらにァスコルビン 酸またはその誘導体およびその他の成分を含有し得る。 この皮膚改善組成物 は、 肌質改善効果を得ること目的として、 例えば、 食品、 医薬品、 医薬部外 品、 化粧品などとして、 各種の形態に調製することができる。  The skin improvement composition of the present invention may further contain ascorbic acid or a derivative thereof and other components in addition to the above essential components. This skin improvement composition can be prepared in various forms as, for example, foods, pharmaceuticals, quasi-drugs, cosmetics, etc. for the purpose of obtaining a skin quality improvement effect.
上述の用途のうち、 本発明の皮膚改善組成物を食品、 医薬品、 医薬部外品 などとして経口摂取する場合、 その形態に特に制限はない。 例えば、 ハード カプセル、 ソフトカプセルなどのカプセル剤、 錠剤、 丸剤、 粉末 (散剤) 、 顆粒、 ティーバッグ、 飴状の粘稠な液体、 液体などの当業者が食品に通常用 いる形態で利用される。 これらは、 形状または好みに応じて、 そのまま摂取 してもよく、 あるいは水、 湯、 牛乳などに溶いて飲んでもよく、 成分を浸出 させたものを摂取してもよい。  Among the above-mentioned uses, when the skin improvement composition of the present invention is orally ingested as food, pharmaceuticals, quasi drugs, etc., there is no particular limitation on the form. For example, capsules such as hard capsules and soft capsules, tablets, pills, powder (powder), granules, tea bags, bowl-like viscous liquids, liquids, etc. are used in a form commonly used by those skilled in the art . Depending on the shape or preference, these may be taken as they are, or may be taken by dissolving in water, hot water, milk, etc., or may be taken after leaching the ingredients.
本発明の皮膚改善組成物を医薬部外品、 化粧品などとして皮膚に塗布する 場合にも、 これらの形態に特に制限はなく、 軟膏剤、 クリーム剤、 乳液、 口 ーシヨン、 パック、 湿布剤、 浴用剤などの従来皮膚外用剤に用いられる形態 であればいずれでもよい。 また、 マウスゥォッシュ、 歯磨き粉、 目薬などの 口 J3空内あるいは目などの粘膜に適用するために適した形態であつてもよく、 これらは同様の作用によって、 粘膜の強化及び保護作用を得ることができる。 本発明の皮膚改善組成物は、 プロアントシァ-ジンおよびコラーゲン産生 促進効果を有するアミノ酸を含有し、 該組成物でなる食品、 医薬品などを摂 取することあるいは化粧品などを皮膚に塗布することによって、 コラーゲン 量を増加させ、 優れた肌質改善効果を発揮する。 そして、 この効果は、 コラ 一ゲン産生能力が低下している状態においても得られる。 このように、 本発 明の組成物は、 肌のハリ 'ツヤの改善およびシヮの防止に優れた食品、 医薬 品、 医薬部外品、 化粧品などとして利用され得る。 さらに、 本発明の組成物 は、 プロアントシァニジン、 特に O P Cが優れた抗ストレス効果を有するた め、 間接的にも肌質改善効果 (美容効果) を有する皮膚外用剤または健康食 品として有用である。 Even when the skin improvement composition of the present invention is applied to the skin as a quasi-drug, cosmetics, etc., these forms are not particularly limited, and are for ointments, creams, emulsions, mouth lotions, packs, poultices, baths. Any form may be used as long as it is a form used in conventional skin external preparations such as a preparation. In addition, mouthwash such as mouthwash, toothpaste, eye drops, etc. J3 may be in a form suitable for application to the mucous membrane in the air or eyes, and these can obtain mucosal strengthening and protective action by the same action . The skin improvement composition of the present invention contains a proanthocyanin and an amino acid having an effect of promoting collagen production, and takes in foods, pharmaceuticals, etc. comprising the composition, or applies cosmetics or the like to the skin. Increases the amount and exhibits an excellent skin quality improvement effect. This effect can be obtained even when the ability to produce collagen is reduced. As described above, the composition of the present invention can be used as a food, a pharmaceutical product, a quasi-drug, a cosmetic product, etc. excellent in improving skin firmness and preventing wrinkles. Furthermore, the composition of the present invention is useful as a topical skin preparation or health food that has an effect of improving skin quality (beauty effect) indirectly because proanthocyanidins, especially OPC, have an excellent anti-stress effect. It is.
実施例 Example
以下に実施例を挙げて本発明を説明するが、 本発明がこの実施例により制 限されるものではない。  The present invention will be described below with reference to examples, but the present invention is not limited to these examples.
(製造例:プロアントシァニジンの調製) (Production example: Preparation of proanthocyanidins)
松樹皮 9 0 0 gに精製水 7 . 2 Lを加え、 プレンダー (Waring Blender) で破碎した後、 1 0 0 °Cで 1 0分間加熱した。 次いで、 直ちに濾過して濾液 を得た。 濾過後の残渣を精製水 1 . 8 Lで洗浄し、 濾液と洗浄液とを合わせ て 9 Lの松樹皮粗抽出液を得た。  Purified water (7.2 L) was added to 900 g of pine bark, and the mixture was broken with a blender (Waring Blender) and heated at 100 ° C. for 10 minutes. Then, it was immediately filtered to obtain a filtrate. The residue after filtration was washed with 1.8 L of purified water, and the filtrate and the washing solution were combined to obtain 9 L of a crude pine bark extract.
この粗抽出液を 2 5 °Cまで放冷し、 塩ィ匕ナトリウムを 1 0 0 %飽和濃度と なるまで添カ卩してよく攪拌した後、 4 °Cで 2 4時間静置した。 静置後、 この 溶液を濾過して濾液を得た。 1 Lの上記濾液を以下に示す工程によりさらに 精製した。 まず、 水で膨潤させた芳香族系合成樹脂 (ダイアイオン H P— 2 0 :三菱化学株式会社製) を 1 0 0 m L充填した 3 0 X 3 0 0 mmの力ラム に上記濾液を通液し、 さらに 1 Lの精製水で洗浄した。 次いで、 カラムから 1 5 % (V/V) のェタノール一水混合溶媒で溶出し、 2 0 0 m Lの精製松 樹皮抽出物を得た。 得られた精製松樹皮抽出物を凍結乾燥して粉末化した。 本操作を繰り返して、 9 Lの松樹皮の熱水抽出液から精製松樹皮抽出物の乾 燥粉末 7. 2 1 gを得た。 この精製松樹皮抽出物の乾燥粉末は、 プロアント シァニジンを 40重量% (OPCとして 20重量0 /0) 含有していた。 The crude extract was allowed to cool to 25 ° C., sodium chloride was added to 100% saturated concentration and stirred well, and then allowed to stand at 4 ° C. for 24 hours. After standing, this solution was filtered to obtain a filtrate. 1 L of the above filtrate was further purified by the steps shown below. First, the filtrate was passed through a 30 x 300 mm force ram filled with 100 ml of an aromatic synthetic resin swollen with water (Diaion HP—20: manufactured by Mitsubishi Chemical Corporation). And further washed with 1 L of purified water. Subsequently, the column was eluted with 15% (V / V) ethanol mixed solvent in ethanol to obtain 200 mL of purified pine bark extract. The purified pine bark extract obtained was freeze-dried and powdered. Repeat this procedure to dry the purified pine bark extract from 9 L pine bark hot water extract. A dry powder of 7.21 g was obtained. Dry powder of the purified pine bark extract, a Puroanto Shianijin 40 wt% (20 wt 0/0 as OPC) contained.
(参考例:プロアントシァニジンの肌質改善効果の確認) (Reference example: confirmation of skin quality improvement effect of proanthocyanidins)
プロアントシァニジンの基本的な肌質改善効果を確認するために、 予め皮 膚のコラーゲン量を減少させた試験モルモットにプロアントシァニジンを経 皮投与 (塗布) あるいは経口投与 (経口摂取) し、 投与後に皮膚を構成する コラーゲンに特異的に存在するハイドロキシプロリン (Hy p量) を測定し た。  In order to confirm the basic skin quality-improving effect of proanthocyanidins, proanthocyanidins were administered dermally (application) or orally (orally ingested) to test guinea pigs whose skin collagen content had been reduced in advance. After the administration, hydroxyproline (hyp amount) specifically present in collagen constituting the skin was measured.
1. 試験モルモットの調製  1. Preparation of test guinea pig
平均体重 2 79 gの雄性モルモッ ト (日本エスエルシー (株) ) 30匹に 基本飼料 (CG— 7 : 日本クレア (株) 、 ビタミン C含有量 0. 1 7重 量%) を一週間与えて馴化させた。 このモルモッ トを総無作為化法により一 群 5匹ずつ割り振った。 6群のモルモット (a〜f 群) のうち、 1群のモル モッ ト (f群) は、 その後も基本飼料を摂取させ、 対照群とした。 5群のモ ルモッ ト (a〜e群) に低ビタミン C飼料 (CG— 7 : 日本クレア (株) 、 ビタミン C含有量 0. 0 1重量0 /0) を 2週間自由摂取させ、 低ビタミン C状 態にすることによって、 皮膚のコラーゲン量 (Hy p量) を減少させた。 こ れらを試験モルモットとした。 30 male guinea pigs with an average body weight of 279 g (Japan SLC Co., Ltd.) were given a basic diet (CG-7: Nippon Claire Co., Ltd., vitamin C content 0.17 wt%) for one week. Accustomed. The guinea pigs were allocated in groups of 5 by a randomized method. Of the 6 groups of guinea pigs (groups a to f), one group of guinea pigs (group f) continued to receive basic feed and served as a control group. Into 5 groups of Mo Rumo' bets (a to e group) low Vitamin C diet (CG-7: Japan CLEA Co., vitamin C content 0.0 1 wt 0/0) was 2 weeks ad libitum, low vitamin By changing to the C state, the amount of collagen (Hy p) in the skin was reduced. These were designated as test guinea pigs.
2. 経皮投与による肌質改善効果の確認  2. Confirmation of skin quality improvement effect by transdermal administration
上記の 5群の試験モルモットのうち、 3群の試験モルモット ( a〜 c群) を用いた。 まず、 3群のモルモッ トの経皮投与する部位の毛をバリカンを用 いて除去した。 上記製造例で得られた松樹皮抽出物の乾燥粉末を 0. 3重 量%含有する水溶液を、 1群のモルモット (a群) の毛を除去した部位に 5 00 μ L/5 00 cm 2の割合で塗布し、 その後、 冷風で乾燥させた。 この 塗布おょぴ乾燥の操作を一日一回の頻度で 2週間行った。 塗布期間中、 モル モットには、 低ビタミン C飼料を自由摂取させた。 Of the five groups of test guinea pigs, three groups of test guinea pigs (groups a to c) were used. First, the hair of the site of the three groups of guinea pigs to be administered transdermally was removed using a clipper. The aqueous solution to a dry powder of the obtained pine bark extract in Preparation containing 0.3 by weight%, a group of guinea pigs site hair was removed the (a group) 5 00 μ L / 5 00 cm 2 And then dried with cold air. This coating and drying operation was performed once a day for 2 weeks. During the application period, mol Mottos were given low vitamin C diet ad libitum.
塗布期間終了後、 皮膚の Hy p量を以下のようにして測定した。 モルモッ トから皮膚を摘出し、 60°Cにて一晩乾燥した。 この乾燥物を粉碎し、 粉枠 物 5 Omgを 5mLの塩酸 (6M) に添力 Pし、 ヒーティングプロックを用い て 110°Cに保持し、 24時間加水分解した。 この加水分解物中の Hy pi をクロラミン T法により測定した。 結果を表 1に示す。 なお、 Hy p量が多 いほど、 皮膚のコラーゲン量が多く、 皮膚が改善されていることを示す。 残りの 2群の毛を除去した試験モルモッ ト (b群および c群) には、 プロ アントシァェジンを 38重量%含有するブドウ種子抽出物 (キッコーマン株 式会社) を 0. 3重量%含有する水溶液および精製水をそれぞれ塗布し、 上 記と同様にして、 皮膚の Hy p量を測定した。 結果を表 1に示す。  After the application period, the amount of skin hypops was measured as follows. The skin was removed from the guinea pig and dried overnight at 60 ° C. This dried product was pulverized, and 5 Omg of the powder frame was added to 5 mL of hydrochloric acid (6M), maintained at 110 ° C using a heating block, and hydrolyzed for 24 hours. Hy pi in this hydrolyzate was measured by the chloramine T method. The results are shown in Table 1. The higher the amount of hypo, the greater the amount of collagen in the skin, indicating that the skin is improved. The test guinea pigs (groups b and c) from which the remaining two groups of hair had been removed contained an aqueous solution containing 0.3% by weight of grape seed extract (Kikkoman Corporation) containing 38% by weight of proanthocyanidin. Purified water was applied to each skin, and the amount of hypo in the skin was measured in the same manner as described above. The results are shown in Table 1.
3. 経口投与による肌質改善効果の確認  3. Confirmation of skin quality improvement effect by oral administration
残りの 2群の試験モルモッ ト (d群および e群) のうち、 1群の試験モル モット (d群) に、 上記製造例で得られた松樹皮抽出物の乾燥粉末を 0. 3 重量%含有する低ビタミン C飼料を 2週間自由摂取させた。 摂取期間終了後、 上記と同様に Hyp量を測定した。 残りの 1群の試験モルモット (e群) に は、 プロアントシァニジンを 38重量%含有するプドウ種子抽出物 (キッコ 一マン株式会社) を 0. 3重量%含有する低ビタミン C飼料を上記と同様に 摂取させ、 Hyp量を測定した。 これらの結果を表 1に示す。 Of the remaining two groups of test guinea pigs (groups d and e), one group of test guinea pigs (group d) was mixed with 0.3% by weight of the dry powder of the pine bark extract obtained in the above production example. The low-vitamin C diet contained was freely given for 2 weeks. After the intake period, the amount of Hyp was measured as described above. The remaining one group of test guinea pigs (e group) contains a low vitamin C diet containing 0.3% by weight of pudo seed extract (Kikko Isman Co., Ltd.) containing 38% by weight of proanthocyanidins. Ingested in the same manner and measured the amount of Hyp. These results are shown in Table 1.
表 1 table 1
Figure imgf000016_0001
Figure imgf000016_0001
平均値 ±標準誤差 Mean value ± standard error
* 1…プロアントシァニジン * 1… Proanthocyanidins
* 2…プロアントシァニジン 40重量%含有  * 2… Proanthocyanidin 40% by weight
* 3…プロアントシァニジン 38重量%含有  * 3 ... Contains 38% by weight of proanthocyanidins
* 4…投与前 2週間低ビタミン C飼料自由摂取  * 4… Free intake of low vitamin C diet for 2 weeks before administration
* 5…投与前 2週間基本飼料自由摂取  * 5… Basic diet free for 2 weeks before administration
表 1の結果から、 松樹皮抽出物おょぴブドウ種子抽出物を塗布あるいは経 口摂取した群 (プロアントシァニジン投与群) は、 精製水のみ塗布した群From the results shown in Table 1, the group that applied or orally ingested the pine bark extract or the opi grape seed extract (the group that received proanthocyanidins) was the group that applied only purified water.
(プロアントシァニジン非投与群) に比べて、 H y p量が増加し、 さらに健 常体 (対照) とほぼ同等の H y p量まで回復していることから、 皮膚改善効 果を有することが分かる。 特に、 松樹皮抽出物は、 他の植物抽出物に比べて 優れた皮膚改善効果を有することが分かる。 Compared to the group not treated with proanthocyanidins, the Hyp amount increased, and the Hyp amount recovered to almost the same level as the healthy subject (control). I understand. In particular, it can be seen that the pine bark extract has an excellent skin improvement effect compared to other plant extracts.
(実施例 1 :飼料 1の調製) (Example 1: Preparation of feed 1)
上記製造例で得られた松樹皮抽出物の乾燥粉末 (A成分) およびプロリン (B成分) を低ビタミン C飼料に表 2に記載の割合で混合して飼料 1を製造 した。  The dry powder (component A) and proline (component B) of the pine bark extract obtained in the above production example were mixed with the low vitamin C feed in the proportions shown in Table 2 to produce feed 1.
(実施例 2〜4 :飼料 2〜4の調製) プロリン ( B成分) の代わりに、 他の B成分として、 ァラニン、 グリシン、 およびアルギニンをそれぞれ用いたこと以外は、 実施例 1と同様にして、 表 2に記載の割合で混合して、 各々飼料 2〜4を製造した。 (Examples 2 to 4: Preparation of feed 2 to 4) In the same manner as in Example 1 except that alanine, glycine, and arginine were used as other B components instead of proline (B component), and mixed in the proportions shown in Table 2, respectively. 2-4 were produced.
(実施例 5 :飼料 5の調製) (Example 5: Preparation of feed 5)
実施例 1の組成に、 さらに。成分としてァスコルビン酸を表 2に記載の割 合で混合したこと以外は、 実施例 1と同様にして、 飼料 5を製造した。  In addition to the composition of Example 1. A feed 5 was produced in the same manner as in Example 1 except that ascorbic acid was mixed as a component at a ratio shown in Table 2.
(比較例 1および 2 :飼料 6および 7の調製) (Comparative Examples 1 and 2: Preparation of feed 6 and 7)
表 2に記載の成分を混合して飼料をそれぞれ製造し、 これらを飼料 6およ び 7とした。  Feeds were produced by mixing the ingredients listed in Table 2, and these were designated as feeds 6 and 7.
(実施例 6 :皮膚改善組成物の経口投与による検討) (Example 6: Examination by oral administration of skin improvement composition)
平均体重が 2 6 7 gの雄性モルモッ ト (日本エスエルシー (株) ) 3 5匹 に基本飼料を一週間与えて馴化させた。 このモルモットを総無作為化法によ り一群 5匹ずつ割り振った。 各群すベてのモルモットを上記参考例と同様に して、 低ビタミン C飼料を 2週間自由摂取させ、 試験モルモッ トとした。 松 樹皮抽出物の乾燥粉末を 0 . 3重量%含有する低ビタミン C飼料の代わりに、 上記飼料 1〜 7を用いたこと以外は、 参考例の 「経口投与による肌質改善効 果の確認」 と同様にして、 H y p量を測定し、 皮膚改善効果を評価した。 結 果を表 2に示す。 表 2 Three male guinea pigs (Japan SLC) with an average body weight of 2 67 g were fed with a basic diet for one week to acclimatize. The guinea pigs were allotted 5 by group using the total randomization method. All groups of guinea pigs were allowed to take a low vitamin C diet ad libitum for 2 weeks in the same manner as in the above Reference Example, and used as test guinea pigs. Except for using the above feeds 1 to 7 instead of the low vitamin C feed containing 0.3% by weight of dry powder of pine bark extract, “Checking the effect of improving skin quality by oral administration” in the Reference Example In the same manner as above, the amount of Hyp was measured to evaluate the skin improvement effect. The results are shown in Table 2. Table 2
Figure imgf000018_0001
Figure imgf000018_0001
成分の単位は重量% 成分の残部は低ビタミン c飼料 Ingredients are in weight percent. Ingredients are low vitamin c feed.
* 1…結果の数値は平均値 ±標準誤差を示す * 1… Results are average values ± standard error
* 2…松樹皮抽出物の乾燥粉末 (プロアントシァニシ 'ン 40重量 %含有)  * 2… Dry powder of pine bark extract (containing 40% by weight of proanthocyanin)
表 2の結果より、 実施例のプロアントシァニジン (A成分) およびァミノ 酸 (B成分) を含有する飼料 1 5 (実施例 1 5 ) を摂取した群は、 比較 例の A成分および B成分のいずれか一方を含有する飼料 6および 7 (比較例 1および 2 ) に比べて、 H y p量が増加していた。 このことは、 A成分およ ぴ B成分を含有する飼料を摂取することによって、 肌質が改善され、 優れた 皮膚改善効果が得られることを示す。 特に、 実施例 5の A成分および B成分 に加えて、 ァスコルビン酸 (C成分) を含有する飼料 5を摂取した群は、 H y p量がさらに増加した。 From the results in Table 2, the group that received the feed 15 containing the proanthocyanidins (A component) and the amino acid (B component) of the example (Example 15) was compared with the A component and B component of the comparative example. Compared with feeds 6 and 7 (Comparative Examples 1 and 2) containing either of these, the amount of Hyp was increased. This indicates that the intake of feed containing component A and component B improves skin quality and provides an excellent skin improvement effect. In particular, in the group that ingested feed 5 containing ascorbic acid (C component) in addition to the A component and B component of Example 5, the amount of Hyp further increased.
(実施例 7〜: L 1 ) (Example 7-: L 1)
表 3に記載の成分を表 3に記載の割合で基剤 (エタノール 5重量%および グリセリン 3重量%を含有する水溶液) に溶解させ、 試料液 1 - 5をそれぞ れ調製した。 (比較例 3および 4 ) The components listed in Table 3 were dissolved in the base (an aqueous solution containing 5% by weight of ethanol and 3% by weight of glycerin) in the proportions described in Table 3 to prepare sample solutions 1-5, respectively. (Comparative Examples 3 and 4)
表 3に記載の成分を表 3に記載の割合で基剤 (ェタノール 5重量%および グリセリン 3重量%を含有する水溶液) に溶解させ、 試料液 6および 7をそ れぞれ調製した。  The components shown in Table 3 were dissolved in the base (an aqueous solution containing 5% by weight of ethanol and 3% by weight of glycerin) in the proportions shown in Table 3 to prepare sample solutions 6 and 7, respectively.
(実施例 1 2 :皮膚改善組成物の経皮投与による検討) (Example 12: Examination by transdermal administration of skin improvement composition)
平均体重が 2 7 2 gの雄性モルモット (日本エスエルシー (株) ) 3 5匹 に基本飼料を一週間与えて馴化させた。 このモルモットを総無作為化法によ り一群 5匹ずつ 7群にわけた。 各群すベてのモルモットを上記参考例と同様 にして、 低ビタミン C飼料を 2週間自由摂取させ、 皮膚のコラーゲン量を減 少させた試験モルモットとした。 松樹皮抽出物の乾燥粉末を 0 . 3重量%含 有する水溶液の代わりに、 上記試料液 1〜 7を用いたこと以外は、 参考例の 「経皮投与による肌質改善効果の確認」 と同様に操作し、 H y p量を測定し、 皮膚改善効果を評価した。 結果を表 3に示す。 表 3  Three 5 male guinea pigs with an average body weight of 2 72 g (Japan SLC Co., Ltd.) were acclimated with a basic diet for one week. The guinea pigs were divided into 7 groups of 5 animals per group by the total randomization method. All the guinea pigs in each group were treated as in the above reference example, and the test guinea pigs were allowed to freely consume a low vitamin C diet for 2 weeks to reduce the amount of collagen in the skin. Similar to “Confirmation of skin quality improvement effect by transdermal administration” in Reference Example, except that the above sample solutions 1 to 7 were used instead of the aqueous solution containing 0.3% by weight of dry powder of pine bark extract. The amount of Hyp was measured and the skin improvement effect was evaluated. The results are shown in Table 3. Table 3
Figure imgf000019_0001
Figure imgf000019_0001
分の 位は重 % 成分の残部は基剤 Minutes are heavy% The rest of the ingredients are base
* 1…結果の数値は平均値土標準誤差を示す * 1… Results indicate average soil standard error
* 2 · "松樹皮抽出物の乾燥粉末 (プロアントシァニシ 'ン 40重量 %含有) 表 3の結果より、 実施例のプロアントシァニジン (A成分) およびァミノ 酸 (B成分) を含有する試料液 1〜 5 (実施例 7〜 1 1 ) を塗布した群は、 比較例の A成分および B成分のいずれか一方を含有する試料液 6および 7 (比較例 3および 4) を塗布した群に比べて、 Hy p量が増加していた。 こ のことは、 A成分および B成分を含有する試料液を塗布することによって、 肌質が改善され、 優れた皮膚改善効果が得られることを示す。 特に、 実施例 1 1の A成分および B成分に加えて、 ァスコルビン酸 (C成分) を含有する 試料液 5を塗布した群は、 H y p量がさらに増加した。 * 2 · “Dry bark extract powder (containing 40% by weight proanthocyanin) From the results in Table 3, the groups to which the sample solutions 1 to 5 (Examples 7 to 11) containing the proanthocyanidins (A component) and the amino acids (B component) of Examples were applied were The amount of Hyp increased compared to the group to which sample solutions 6 and 7 (Comparative Examples 3 and 4) containing one of the component and component B were applied. This indicates that application of a sample solution containing component A and component B improves the skin quality and provides an excellent skin improvement effect. In particular, in the group to which sample solution 5 containing ascorbic acid (component C) in addition to the components A and B of Example 11 was applied, the amount of Hyp further increased.
(実施例 13 :錠剤 1の製造) (Example 13: Production of tablet 1)
製造例で得られた松樹皮抽出物の乾燥粉末 (A成分) 、 プロリン、 ァラ- ン、 グリシン、 アルギニン (以上、 B成分) 、 アルコルビン酸 (C成分) 、 および賦形剤 (結晶セルロース、 ショ糖エステル、 還元麦芽糖、 二酸化ケィ 素、 および卵殻カルシウムを重量比で 1 : 0. 3 : 0. 1 : 0. 2 : 4の割 合で混合した混合物) を表 4に記載の割合にて混合して錠剤 (1錠当たり、 約 200mg) を製造し、 これを錠剤 1とした。  Pine bark extract dry powder (A component), proline, allan, glycine, arginine (above, B component), ascorbic acid (C component), and excipients (crystalline cellulose, Table 4 shows a mixture of sucrose ester, reduced maltose, carbon dioxide, and eggshell calcium in a weight ratio of 1: 0.3: 0.1: 0.2: 4). Tablets (about 200 mg per tablet) were produced by mixing, and this was designated as Tablet 1.
(比較例 5 :錠剤 2の製造) (Comparative Example 5: Production of tablet 2)
松樹皮抽出物の乾燥粉末を用いなかったこと以外は、 実施例 13と同様に して、 表 4に記載の割合にて混合して錠剤 (1錠当たり、 約 200mg) を 製造し、 これを錠剤 2とした。  Except that the dry powder of pine bark extract was not used, a tablet (about 200 mg per tablet) was produced by mixing at the ratio shown in Table 4 in the same manner as in Example 13. Tablet 2 was designated.
(実施例 14 :化粧水 1の製造) (Example 14: Production of lotion 1)
製造例で得られた松樹皮抽出物の乾燥粉末 (A成分) 、 プロリン、 ァラニ ン、 グリシン、 アルギニン (以上、 B成分) 、 およびアルコルビン酸 (C成 分) を表 4に記載の割合にて基剤 (グリセリン 3重量。/。、 プロピレングリコ ール 2重量%、 およびエタノール 5重量%含有する水溶液) に溶解させ、 ィ匕 粧水 1を製造した。 The dry powder (component A), proline, alanine, glycine, arginine (above component B), and alcorbic acid (component C) obtained in the production example in the proportions shown in Table 4 Base (glycerin 3 wt./., Propylene glycol Solution of 2% by weight of ethanol and 5% by weight of ethanol).
(比較例 6 :化粧水 2の製造) (Comparative Example 6: Production of lotion 2)
松樹皮抽出物の乾燥粉末を用いなかったこと以外は、 実施例 1 4と同様に して、 表 4に記載の割合にて基剤に溶解させ、 化粧水 2を製造した。  A lotion 2 was produced in the same manner as in Example 14 except that the dry powder of pine bark extract was not dissolved in the base at the ratio shown in Table 4.
(実施例 1 5 :皮膚改善組成物のヒトによる評価) (Example 15: Evaluation of human skin improvement composition)
3 0〜4 5歳の女性 (被験者) 2 0名を 4群に分けた。 1群の被験者に実 施例 1 3の錠剤 1を 1日あたり 1 8錠の割合で 1ヶ月間摂取させた。 他の 1 群の被験者には比較例 5の錠剤 2を上記と同様の条件で摂取させた。 摂取期 間終了後、 各群の被験者に対して、 摂取前に比べて、 肌の状態に関する表 5 に記載の項目をアンケート調査し、 皮膚改善効果を評価した。 アンケート調 查は、 「はい」 または 「いいえ」 で自己評価してもらい、 「はい」 と答えた 人数を集計した。 結果を表 5に示す。  3 0-4 5 year old female (subject) 20 were divided into 4 groups. One group of subjects ingested tablet 1 of Example 1 3 at a rate of 18 tablets per day for 1 month. The other group of subjects ingested Tablet 2 of Comparative Example 5 under the same conditions as described above. After the intake period, the subjects in each group were surveyed on the items listed in Table 5 regarding the skin condition compared to before the intake, and the skin improvement effect was evaluated. In the questionnaire survey, the number of people who answered “Yes” was calculated by “Yes” or “No”. The results are shown in Table 5.
残りの 2群の被験者のうち、 1群の被験者において、 実施例 1 4の化粧水 1を被験者の顔に 1日に 3回の頻度で 1ヶ月間塗布してもらった。 なお、 1 回あたりの塗布量の制限は設定しなかった。 別の 1群の被験者には、 比較例 6の化粧水 2を上記と同様の条件で塗布してもらつた。 塗布期間期間終了後、 各群の被験者に対して、 上記と同様に表 5に記載の項目をアンケート調查し、 皮膚改善効果を評価した。 結果を表 5に示す。 表 4 Of the remaining 2 groups of subjects, in 1 group of subjects, the skin lotion 1 of Example 14 was applied to the face of the subject 3 times a day for 1 month. There was no restriction on the amount of application per application. Another group of subjects was given lotion 2 of Comparative Example 6 under the same conditions as above. After completion of the application period, the items listed in Table 5 were surveyed in the same manner as above for the subjects in each group, and the skin improvement effect was evaluated. The results are shown in Table 5. Table 4
Figure imgf000022_0001
Figure imgf000022_0001
単位は重量% 錠剤の残部は賦形剤 化粧水の残部は基剤 Unit:% by weight The remainder of the tablet is an excipient The remainder of the skin lotion is the base
* 1…松樹皮抽出物の乾燥粉末 (プロアントシァニシ 'ン 40重量 %含有) * 1… Dry powder of pine bark extract (containing 40% by weight of proanthocyanin)
表 5 Table 5
Figure imgf000022_0002
Figure imgf000022_0002
数値は「はい」と答えた人数  The number is the number of people who answered yes
表 5の結果から、 実施例 1 3の錠剤 1を摂取した群は、 比較例 5の錠剤 2 を摂取した群に比べて優れた皮膚改善効果を有することがわかる。 実施例 1 4の化粧水 1を塗布した群は、 比較例 6の化粧水 2を塗布した群に比べて優 れた皮膚改善効果を有することがわかる。 以上のことから、 本発明の皮膚改 善組成物は、 経口投与および経皮投与のいずれにおいても優れた皮膚改善効 果が得られることが分かる。 From the results of Table 5, it can be seen that the group ingesting tablet 1 of Example 13 has an excellent skin improvement effect compared to the group ingesting tablet 2 of Comparative Example 5. It can be seen that the group to which the lotion 1 of Example 14 was applied had an excellent skin improvement effect as compared to the group to which the lotion 2 of Comparative Example 6 was applied. From the above, the skin improvement composition of the present invention has an excellent skin improvement effect in both oral administration and transdermal administration. It turns out that a fruit is obtained.
(実施例 1 6 ) (Example 16)
製造例で得られた松樹皮抽出物の乾燥粉末および以下の各成分を混合して 飲料を調製した:  A beverage was prepared by mixing the dry powder of the pine bark extract obtained in Production Example and the following ingredients:
く飲料の配合成分 > 配合重量 (1 Lあたり) 果糖プドウ糖液糖 1 0 g Ingredients for beverages> Blending weight (per liter) Fructose pudou sugar liquid sugar
レモン果汁 1 0 g  Lemon juice 1 0 g
クェン酸 2 g  Chenic acid 2 g
; L—ァスコルビン酸 2 g  L-ascorbic acid 2 g
松樹皮抽出物 7 0 m g 香料 1 5 0 m g グリシン 1 0 O m g プロリン 1 0 0 m g ァラニン 8 O m g アルギニン 4 0 m g 純水  Pine bark extract 7 0 mg Fragrance 1 5 0 mg Glycine 1 0 O mg Proline 1 0 0 mg Alanine 8 O mg Arginine 4 0 mg Pure water
(実施例 1 7 ) (Example 1 7)
製造例で得られた松樹皮抽出物の乾燥粉末および以下の各成分を均一に攪 拌混合して、 ゲル状物を得、 'これをポリエステルフィルム (5 0 /i m厚) 上 にゲル厚 l mmとなるように製膜した後、 ポリエステル不織布 (伸度 5 0 %) に貼り合わせて、 5 0 °Cで 2 4時間加温し、 シート状含水パック剤を 得た。 本パックは、 局所的に多量のプロアントシァニジンおよびアミノ酸を 経皮投与できるため、 その効果が極めて高いことが期待できる:  The dry powder of the pine bark extract obtained in the production example and the following components were uniformly stirred and mixed to obtain a gel-like product, which was then applied to a polyester film (50 / im thickness) with a gel thickness l After forming the film to a thickness of mm, it was bonded to a polyester nonwoven fabric (elongation 50%) and heated at 50 ° C. for 24 hours to obtain a sheet-like water-containing pack agent. This pack is expected to be extremely effective because it can be transdermally administered in large amounts locally on proanthocyanidins and amino acids:
<パックの配合成分 > (単位は重量%) 松樹皮抽出物 0. 01 ポリアクリル酸 (重量平均分子量: 500万) 6. 0 プロリン 0. 2 ァラニン 0. 1 グリシン 0. 2 ァノレギユン 0. 1 パルミチン酸ァスコルビル 0. 01 グリセリン 20. 0 エタノーノレ 0. 5 パラォキシ安息香酸エステル 0. 1 香料 (ミント) 0. 1 乾燥水酸ィ匕ァノレミニゥムゲル 0. 35 水 残量 産業上の利用可能性 <Pack ingredients> (Unit:% by weight) Pine bark extract 0. 01 Polyacrylic acid (weight average molecular weight: 5 million) 6.0 Proline 0. 2 Alanine 0. 1 Glycine 0. 2 Anolegiyun 0. 1 Ascorbyl palmitate 0. 01 Glycerin 20. 0 Ethanol No. 0. 5 Paraxybenzoate 0.1. Perfume (Mint) 0.1. Dry Hydroxylanoreminum Gel 0.35 Water Remaining Industrial Applicability
以上のように、 プ Pアントシァニジンと、 コラーゲン産生促進効果を有す るアミノ酸とを含有する皮膚改善糸且成物を摂取することあるいは塗布するこ とにより、 優れた皮膚改善効果が得られる。 本発明の皮膚改善組成物は、 食 品、 医薬品、 医薬部外品、 化粧品などに効果的に利用され得る。  As described above, an excellent skin improvement effect can be obtained by ingesting or applying a skin improvement thread and composition containing p-Panthocyanidin and an amino acid having a collagen production promoting effect. The skin improvement composition of the present invention can be effectively used for foods, pharmaceuticals, quasi drugs, cosmetics and the like.

Claims

請求の範囲 The scope of the claims
1 . プロアントシァニジンと、 コラーゲン産生促進効果を有するアミノ酸と を含有する、 皮膚改善組成物。 1. A skin improvement composition comprising proanthocyanidins and an amino acid having a collagen production promoting effect.
2 . さらに、 ァスコルビン酸またはその誘導体を含有する、 請求項 1に記載 の皮膚改善組成物。 2. The skin improvement composition according to claim 1, further comprising ascorbic acid or a derivative thereof.
3 . 前記プロアントシァニジンが、 松樹皮由来である、 請求項 1または 2に 記載の皮膚改善組成物。 3. The skin improvement composition according to claim 1 or 2, wherein the proanthocyanidins are derived from pine bark.
PCT/JP2004/018777 2004-12-09 2004-12-09 Skin remedy composition WO2006061915A1 (en)

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Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02134309A (en) * 1988-11-16 1990-05-23 Kikkoman Corp Beautifying and whitening cosmetic
JPH07194375A (en) * 1993-12-28 1995-08-01 Kanebo Ltd Promoter for synthesizing collagen and collagen metabolism activator
US5804594A (en) * 1997-01-22 1998-09-08 Murad; Howard Pharmaceutical compositions and methods for improving wrinkles and other skin conditions
JPH1149628A (en) * 1997-07-31 1999-02-23 Shiseido Co Ltd Cosmetic for improving wrinkle
WO2000051561A1 (en) * 1999-03-02 2000-09-08 Kyowa Hakko Kogyo Co., Ltd. Cosmetics
JP2002119210A (en) * 2000-10-13 2002-04-23 Riken Vitamin Co Ltd Method for producing coffee beverage
JP2003530410A (en) * 2000-04-14 2003-10-14 マーズ インコーポレイテッド Compositions and methods for improving vascular health
JP2004149441A (en) * 2002-10-30 2004-05-27 Toyo Shinyaku:Kk External preparation for skin
JP2004210675A (en) * 2002-12-27 2004-07-29 Toyo Shinyaku:Kk Bone quantity amelioration composition
JP2004307370A (en) * 2003-04-04 2004-11-04 Kyowa Hakko Kogyo Co Ltd Composition containing proanthocyanidin
JP3595816B2 (en) * 2002-04-24 2004-12-02 株式会社東洋新薬 Method for producing proanthocyanidin-containing material
JP2005029486A (en) * 2003-07-09 2005-02-03 Toyo Shinyaku:Kk Skin-improving composition

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02134309A (en) * 1988-11-16 1990-05-23 Kikkoman Corp Beautifying and whitening cosmetic
JPH07194375A (en) * 1993-12-28 1995-08-01 Kanebo Ltd Promoter for synthesizing collagen and collagen metabolism activator
US5804594A (en) * 1997-01-22 1998-09-08 Murad; Howard Pharmaceutical compositions and methods for improving wrinkles and other skin conditions
JPH1149628A (en) * 1997-07-31 1999-02-23 Shiseido Co Ltd Cosmetic for improving wrinkle
WO2000051561A1 (en) * 1999-03-02 2000-09-08 Kyowa Hakko Kogyo Co., Ltd. Cosmetics
JP2003530410A (en) * 2000-04-14 2003-10-14 マーズ インコーポレイテッド Compositions and methods for improving vascular health
JP2002119210A (en) * 2000-10-13 2002-04-23 Riken Vitamin Co Ltd Method for producing coffee beverage
JP3595816B2 (en) * 2002-04-24 2004-12-02 株式会社東洋新薬 Method for producing proanthocyanidin-containing material
JP2004149441A (en) * 2002-10-30 2004-05-27 Toyo Shinyaku:Kk External preparation for skin
JP2004210675A (en) * 2002-12-27 2004-07-29 Toyo Shinyaku:Kk Bone quantity amelioration composition
JP2004307370A (en) * 2003-04-04 2004-11-04 Kyowa Hakko Kogyo Co Ltd Composition containing proanthocyanidin
JP2005029486A (en) * 2003-07-09 2005-02-03 Toyo Shinyaku:Kk Skin-improving composition

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