JP2011105695A - Peroral hair-growth stimulant - Google Patents

Peroral hair-growth stimulant Download PDF

Info

Publication number
JP2011105695A
JP2011105695A JP2009276977A JP2009276977A JP2011105695A JP 2011105695 A JP2011105695 A JP 2011105695A JP 2009276977 A JP2009276977 A JP 2009276977A JP 2009276977 A JP2009276977 A JP 2009276977A JP 2011105695 A JP2011105695 A JP 2011105695A
Authority
JP
Japan
Prior art keywords
extract
hair growth
hair
sample
seed extract
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
JP2009276977A
Other languages
Japanese (ja)
Other versions
JP5617110B2 (en
Inventor
Tsutomu Nozaki
勉 野崎
Keiko Kono
恵子 河野
Takeo Ishihara
健夫 石原
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BHN Co Ltd
Original Assignee
BHN 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 BHN Co Ltd filed Critical BHN Co Ltd
Priority to JP2009276977A priority Critical patent/JP5617110B2/en
Publication of JP2011105695A publication Critical patent/JP2011105695A/en
Application granted granted Critical
Publication of JP5617110B2 publication Critical patent/JP5617110B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Inorganic Chemistry (AREA)

Abstract

<P>PROBLEM TO BE SOLVED: To develop a raw material which can be put simply in a dietary life and has the hair growth stimulative-, hair restorative-, and/or hair pilatory-effect, and to provide a composition having a mode of the industrially effective applicability. <P>SOLUTION: The peroral hair growth stimulant includes as effective components a Serenoa repens fruit extract, and a pumpkin seed extract, preferably a cyclodextrin inclusion compound of both the extracts, and a substance having blood flow improving action, preferably a camellia seed extract and/or a green tea-leaf extract; the stimulant can be effectively utilized as food and drink, medicine, quasi-drug, and animal food. The camellia seed extract includes such suitable one that contains a saponin-containing water-soluble component obtained by extraction of defatted matter of camellia seed with water or a lower alcohol. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

本発明は、特定の植物を原料とする発毛促進剤に係る。より詳しくは、ノコギリヤシ、カボチャ、ツバキ及び緑茶等を原料としてなる経口用発毛促進剤に関するものである。The present invention relates to a hair growth promoter made from a specific plant as a raw material. More specifically, the present invention relates to an oral hair growth promoter made from saw palmetto, pumpkin, camellia, green tea and the like.

日常診療で遭遇する脱毛症として、男性型脱毛症(禿頭症)、円形脱毛症、抜毛症があり、また、薬剤による脱毛、感染症による脱毛、腫瘍性脱毛、機械性脱毛症の他、栄養・代謝障害による脱毛、脂漏性脱毛、ホルモン等の内分泌異常による脱毛、分娩後脱毛、粃糠性脱毛症等がある。Alopecia encountered in daily practice includes androgenetic alopecia (baldness), alopecia areata, and alopecia. Also, hair loss due to drugs, hair loss due to infections, tumor hair loss, mechanical alopecia, nutrition -Hair loss due to metabolic disorders, seborrheic hair loss, hair loss due to endocrine abnormalities such as hormones, postpartum hair loss, and alopecia areata.

このうち男性型脱毛症は思春期以降に額の生え際や頭頂部の髪のどちらか一方又は双方から薄くなり、進行していく。この原因は一般的に遺伝や男性ホルモン等が関与すると考えられており、抜け毛が進行し、薄毛が目立つようになる。この男性型脱毛症状のある者の数は我国だけでも1,000万人を超えるともいわれ、その多くが薄毛に悩み、ストレスを感じている。近年、日常生活の精神的ストレスやホルモンバランス障害等から女性でも男性型脱毛症状を呈することが多くなっている。Of these, male pattern baldness progresses after puberty, thinning from one or both of the hairline on the forehead and the hair on the top of the head. This cause is generally considered to be related to heredity, male hormones, etc., and hair loss progresses and thin hair becomes conspicuous. It is said that there are over 10 million people with male pattern hair loss symptoms in our country alone, and many of them suffer from thinning hair and feel stress. In recent years, masculine hair loss symptoms are increasing even in women due to mental stress in daily life and hormonal balance disorder.

男性型脱毛症の主要な原因物質はジヒドロテストステロン(DHT)と呼ばれる物質であるとされ、男性型脱毛症では、脱毛部分の頭皮に多量のDHTが確認されている。DHTはテストステロン5α−還元酵素(以下、単に5α−リダクターゼという)によって男性ホルモンの一種であるテストステロンから作られる。このDHTが毛乳頭細胞に存在する男性ホルモン受容体と結合すると、脱毛シグナルが出され、毛髪の成長期が終了してしまい、毛髪が長く太い毛に成長する前に抜けてしまう。こうして、十分に育たない細く短い毛髪が多くなることで、全体として薄毛が目立つようになる。The main causative substance of male pattern baldness is said to be a substance called dihydrotestosterone (DHT). In male pattern baldness, a large amount of DHT has been confirmed in the scalp of the hair loss part. DHT is made from testosterone, a kind of male hormone, by testosterone 5α-reductase (hereinafter simply referred to as 5α-reductase). When this DHT binds to the androgen receptor present in the dermal papilla cell, a hair loss signal is issued, the hair growth phase ends, and the hair comes off before it grows into long and thick hair. In this way, thin hairs become conspicuous as a whole by increasing the number of thin and short hair that does not grow sufficiently.

このため、男性型脱毛症に対する発毛剤として、5α−リダクターゼ活性を阻害してDHTの産生を抑制する物質の利用が進められている。すなわち、5α−リダクターゼ活性を阻害し、体内でのDHTの産生を低下させて男性型脱毛症を改善する医薬用素材としてフィナステリドを有効成分として含むプロペシア(登録商標)錠が市販され、エストラジオール等の女性ホルモン作用を有する物質やオキセンドロン等の抗男性ホルモン作用を有する物質が頭皮頭髪用外用剤として利用されている。また、植物を原料とする5α−リダクターゼ阻害作用のあるものとしては多種多様の抽出物が提案されており、ノコギリヤシ抽出物(非特許文献1)、ハマナス、ユキノシタ、マンゴスチン等の抽出物(特許文献1)、ガラナ種子エキス(特許文献2)、セージ、ホップ、オトギリソウ、カミツレ、ローズマリー等のハーブ抽出物(特許文献3)、クロレラ、スピルリナ、ユーグレナ等の微細藻類の抽出物(特許文献4)、ツユクサ抽出物(特許文献5)等を例示することができる。For this reason, utilization of the substance which inhibits 5 alpha-reductase activity and suppresses the production | generation of DHT is advanced as a hair growth agent with respect to androgenetic alopecia. That is, Propecia (registered trademark) tablets containing finasteride as an active ingredient are commercially available as pharmaceutical ingredients that inhibit 5α-reductase activity and reduce DHT production in the body to improve male pattern baldness. Substances having a female hormonal action and substances having an anti-androgenic action such as oxendron are used as external preparations for scalp and hair. In addition, a wide variety of extracts have been proposed as plants having 5α-reductase inhibitory activity, such as saw palmetto extract (Non-patent Document 1), extracts such as Hermanus, Yukinoshita, Mangosteen (Patent Document) 1), guarana seed extract (patent document 2), herb extracts such as sage, hop, hypericum, chamomile, rosemary (patent document 3), extract of microalgae such as chlorella, spirulina, euglena (patent document 4) , Cypress extract (Patent Document 5) and the like.

しかしながら、医薬素材やホルモン作用物質は副作用や安全性、使用面で制限があり、従来のさまざまな植物抽出物も実験レベルでの効果は認められても、これを飲食品用途に利用する場合は、胃腸内で変質や分解を受けるリスクがあり、個人によって効果が必ずしも明確でない場合もあり、実用面で有効性を発現し得るものは数少ないのが実情であった。また、植物抽出物の場合、十分な効果を得るためには多量の摂取を必要とすることが多く、長期間の服用が困難であることが多かった。さらに、5α−リダクターゼ阻害物質を頭皮や頭髪に局所適用する化粧料等の外用剤への利用の提案は従来多く見られるが、衛生面から繰り返し使用しなければならず、効率性の点で満足できるものではなかった。また、5α−リダクターゼ阻害物質は発毛促進に寄与する要因であるが、これを単独で適用しても現実的な発毛効果は小さいことも当業者の認識であった。したがって、前記の発毛促進作用を増強し得る実効性のあるものが求められていた。However, pharmaceutical materials and hormonal agents are limited in terms of side effects, safety, and usage, and various conventional plant extracts are effective at the experimental level. However, there is a risk of alteration and degradation in the gastrointestinal tract, and the effect may not always be clear depending on the individual, and there are few things that can be effective in practical use. In the case of plant extracts, in order to obtain a sufficient effect, a large amount of ingestion is often required, and long-term administration is often difficult. Furthermore, there have been many proposals for the use of 5α-reductase inhibitors in topical applications such as cosmetics that are topically applied to the scalp and hair. It wasn't possible. Further, although the 5α-reductase inhibitor is a factor contributing to hair growth promotion, it was also recognized by those skilled in the art that even if this is applied alone, the realistic hair growth effect is small. Therefore, what has the effect which can reinforce the said hair growth promotion effect | action was calculated | required.

特開平5−17365号公報JP-A-5-17365 特開平7−33673号公報JP-A-7-33673 特開平9−221413号公報JP-A-9-212413 特開2002−68943号公報JP 2002-68943 A 特開2007−145739号公報JP 2007-145739 Palin MFら、Endocrine、第9巻、第1号、第65頁〜第69頁、1998年Palin MF et al., Endocrine, Vol. 9, No. 1, pp. 65-69, 1998

かかる現状に鑑み、本発明者らは、より安全で長期間の服用が可能であり、且つ食生活に簡便に組み込むことが可能な、実効性の高い発毛促進剤を開発するとともにこれを産業上有効活用できる態様の組成物を提供することを課題とした。In view of the present situation, the present inventors have developed a highly effective hair growth promoter that can be taken safely and for a long period of time and can be easily incorporated into a diet, and this is used in the industry. Another object of the present invention is to provide a composition that can be effectively utilized.

前記課題を解決するために、本発明者らは、毛髪の発育を効果的に促進する諸条件とそれを満たす素材について鋭意検討した結果、ノコギリヤシ果実の抽出物とカボチャ種子の抽出物とを組み合わせて経口服用すること、さらには、これらと血流改善作用を有する物質とりわけツバキ種子の抽出物及び/又は緑茶葉の抽出物とを併用することが極めて有用であることを見出し、本発明を完成するに至った。In order to solve the above-mentioned problems, the present inventors have intensively studied various conditions for effectively promoting hair growth and materials satisfying the conditions, and as a result, combined an extract of saw palm fruit and an extract of pumpkin seeds. It was found that it is extremely useful to use these in combination with substances that have an effect of improving blood flow, especially extracts from camellia seeds and / or green tea leaf extracts. It came to do.

すなわち、本発明の要旨は、ノコギリヤシ果実の抽出物及びカボチャ種子の抽出物を有効成分として含有してなる経口発毛促進剤である。この経口発毛促進剤においては、ノコギリヤシ果実抽出物及びカボチャ種子抽出物はシクロデキストリンで包接されたものであることが望ましく、さらには、これらと血流改善作用物質とを併用するものがより一層望ましい。そして、この血流改善作用物質はツバキ種子の抽出物及び/又は緑茶葉の抽出物であることが好適であり、とりわけツバキ種子抽出物を用いることがより好ましく、該ツバキ種子抽出物はツバキ種子の脱脂物を水及び/又は低級アルコールで抽出処理して得られる水溶性成分を含むものであり、サポニン類を含有するものであることが最も望ましい態様である。また、本発明では、前記の経口発毛促進剤は飲食品として用いることが望ましく、その好適な形態は粉末状、顆粒状、錠剤状、カプセル状又は液体状のものである。That is, the gist of the present invention is an oral hair growth promoter comprising an extract of saw palm fruit and an extract of pumpkin seed as active ingredients. In this oral hair growth-promoting agent, it is desirable that the saw palm fruit extract and the pumpkin seed extract are clathrated with cyclodextrin, and more preferably a combination of these and a blood flow improving agent. More desirable. The blood flow improving agent is preferably a camellia seed extract and / or a green tea leaf extract, more preferably a camellia seed extract, and the camellia seed extract is preferably a camellia seed extract. The water-soluble component obtained by subjecting the defatted product to extraction with water and / or a lower alcohol is the most desirable aspect. In the present invention, the oral hair growth promoter is preferably used as a food or drink, and its preferred form is powder, granule, tablet, capsule or liquid.

本発明に係るノコギリヤシ果実抽出物及びカボチャ種子抽出物は、これを経口摂取することにより発毛促進、育毛及び/又は養毛の効果を奏する。かかる効果は、ノコギリヤシ果実抽出物及びカボチャ種子抽出物のシクロデキストリン包接物の場合に顕著に発現し、該シクロデキストリン包接物と血流改善作用のあるツバキ種子抽出物及び/又は緑茶葉抽出物とを併用することによってさらに増強される。とりわけ、ツバキ種子抽出物がツバキ種子の脱脂物を水及び/又は低級アルコールで抽出処理して得られる水溶性成分を含むものであり、サポニン類を含有するものであるときに格別顕著な発毛促進効果を奏する。この経口発毛促進剤は飲食品のみならず医薬品、医薬部外品、動物用飼料等の用途において、髪や毛の成長が抑制されたり、薄毛、抜け毛、脱毛等の毛髪トラブルを予防及び/又は改善するために有効利用することができる。The saw palm fruit extract and the pumpkin seed extract according to the present invention have effects of promoting hair growth, hair growth and / or nourishing by ingesting them. Such an effect is remarkably expressed in the case of cyclodextrin inclusions of saw palm fruit extract and pumpkin seed extract, and camellia seed extract and / or green tea leaf extraction having an effect of improving blood flow with the cyclodextrin inclusion extract. It is further enhanced by using it together with the product. In particular, when the camellia seed extract contains a water-soluble component obtained by extracting a camellia seed defatted product with water and / or a lower alcohol and contains saponins, the hair growth is particularly remarkable. Has a promoting effect. This oral hair growth promoter is used not only for food and drink but also for pharmaceuticals, quasi-drugs, animal feeds, etc. to prevent hair and hair growth and to prevent hair troubles such as thinning, hair loss and hair loss. Or it can be used effectively for improvement.

以下に本発明を詳細に説明する。まず、本発明の経口発毛促進剤は、ノコギリヤシの果実の抽出物とカボチャの種子の抽出物とを有効成分として含有してなることを特徴とするものである。The present invention is described in detail below. First, the oral hair growth-promoting agent of the present invention is characterized by containing an extract of saw palm fruit and an extract of pumpkin seed as active ingredients.

ノコギリヤシ(Serenoa repens又はSerenoa serrula)は別名ソウ・パルメット(Saw palmetto)とも呼ばれ、ヤシ科に属する植物であり、北米南部地域に分布しており、その果実に含まれる油性物質が5α−リダクターゼ阻害、前立腺肥大抑制、排尿障害緩和、利尿促進、抗炎症等の作用を有することが知られている。Saw palmetto (Serenoa repens or Serenoa serrula), also known as Saw palmetto, is a plant belonging to the palm family, distributed in the southern region of North America, and the oily substance contained in the fruit is 5α-reductase inhibitor It is known to have actions such as suppressing prostate hypertrophy, alleviating dysuria, promoting diuresis, and anti-inflammatory.

本発明で用いるノコギリヤシ果実抽出物は前記油性物質をいい、未熟あるいは完熟の果実をそのまま又は乾燥物を適宜に細断してノルマルヘキサン、アセトン、エーテル、エタノール等の親油性有機溶媒を用いて抽出するか、二酸化炭素、プロパン、窒素等を用いて超臨界状態下で抽出することにより製造することができる。抽出物の安全性や品質面から超臨界炭酸ガス抽出法が好適である。なお、この抽出物は必要に応じて常法により脱色処理や脱臭処理を施してもよい。前記抽出物として得られる油性物質はカプロン酸、ラウリン酸、パルミチン酸、オレイン酸等の炭素数6〜18の飽和及び不飽和脂肪酸類を主成分として、オクタコサノール、トリアコンタノール等の脂肪族長鎖アルコール類、β−シトステロール、カンペステロール等の植物ステロール類を含み、アルコール類に僅かに溶解するが、水にはほとんど溶けない。The saw palmetto fruit extract used in the present invention refers to the oily substance, and is extracted using a lipophilic organic solvent such as normal hexane, acetone, ether, ethanol, and the like when the immature or ripe fruit is left as it is or the dried product is appropriately shredded. Alternatively, it can be produced by extraction under supercritical conditions using carbon dioxide, propane, nitrogen or the like. The supercritical carbon dioxide extraction method is suitable from the viewpoint of the safety and quality of the extract. This extract may be subjected to decolorization treatment and deodorization treatment by a conventional method as necessary. The oily substance obtained as the extract is mainly composed of saturated and unsaturated fatty acids having 6 to 18 carbon atoms such as caproic acid, lauric acid, palmitic acid and oleic acid, and aliphatic long chain alcohols such as octacosanol and triacontanol. , Β-sitosterol, plant sterols such as campesterol, etc., slightly soluble in alcohols, but hardly soluble in water.

カボチャはウリ科カボチャ属(Cucurbita)に属し、カロテンやビタミン類を多く含む緑黄色野菜として古来より利用されてきた。カボチャの種類は、ナタワレカボチャや栗カボチャのような西洋カボチャ(C.maxima)、鹿ケ谷南瓜や黒皮南瓜等の東洋カボチャ(C.moschata)、及び、金糸うりやズッキーニ等のペポカボチャ(C.pepo)に大別される。通常は果肉を食するが、乾燥種子も食用ナッツ類のカテゴリーで、また、種子から油分を抽出してパンプキンシードオイルとして市販されている。カボチャ種子は、従来、駆虫、利尿、強壮の伝承薬として利用されてきた経緯があり、また、近年では、種子から採取した油脂が前立腺繊維芽細胞における5α−リダクターゼ活性の阻害作用を有し、それに基づき前立腺肥大による泌尿器系症状(排尿の量、時間、頻度等の排尿障害)の治療に有効であるといわれている。Pumpkin belongs to the cucurbita genus (Cucurbita) and has been used since ancient times as a green-yellow vegetable rich in carotene and vitamins. The types of pumpkins are Western pumpkins (C. maxima) such as Nataware pumpkins and chestnut pumpkins, oriental pumpkins (C. moschata) such as Shikagaya Nanban and Kuroshiki Nanban, and peppo pumpkins such as gold thread and zucchini ( C. pepo). Normally, the flesh is eaten, but dried seeds are also in the category of edible nuts, and oil is extracted from the seeds and is marketed as pumpkin seed oil. Pumpkin seeds have a history of being used as a traditional medicine for anthelmintic, diuretic and tonic, and in recent years, oils collected from seeds have an inhibitory action on 5α-reductase activity in prostate fibroblasts, Based on this, it is said to be effective in treating urinary symptoms (urinary dysfunction such as urination volume, time, frequency, etc.) due to enlarged prostate.

本発明に係るカボチャは、前記カボチャ属に属するものであればいずれの種類でも差し支えないが、ペポカボチャに分類されるものが望ましい。この具体例として、Cucurbita aurantia Willd.、Cucurbita melopepo L.、Pepo vulgaris Moench.等を挙げることができる。本発明のカボチャ種子抽出物は、前記カボチャの未熟又は完熟種子を採取し、生のままあるいは適宜に乾燥し、粗砕乃至は細断して、ノルマルヘキサン、アセトン、エーテル等の親油性有機溶媒を用いて抽出するか、超臨界状態の二酸化炭素、プロパン等を用いて抽出することにより製造することができる。抽出物の安全性や品質面から超臨界炭酸ガス抽出法が好ましい。なお、この抽出物は必要に応じて常法により脱色処理や脱臭処理を施してもよい。前記抽出物として得られる油性物質は、オレイン酸、パルミチン酸、ステアリン酸等の炭素数16〜18の飽和及び不飽和脂肪酸類を主要構成脂肪酸とするグリセリドを主成分として、スクアレン、トコフェロール類(β−トコフェロール、γ−トコフェロール等)、ステロール類(スチグマステロール、β−シトステロール、カンペステロール、スピナステロール、アベナステロール等)、脂肪族アルコール類、カロテノイド類(β−カロテン)等を含み、水にほとんど溶解しない。The pumpkin according to the present invention may be of any type as long as it belongs to the pumpkin genus, but is preferably classified as a peppo pumpkin. As a specific example, Cucurbita aurantia Wild. , Cucurbita melopepo L .; Pepo vulgaris Moench. Etc. The pumpkin seed extract of the present invention is a lipophilic organic solvent such as normal hexane, acetone, ether, which is obtained by collecting immature or ripe seeds of the pumpkin, raw or appropriately dried, crushed or shredded Or by using supercritical carbon dioxide, propane, or the like. The supercritical carbon dioxide extraction method is preferable from the viewpoint of the safety and quality of the extract. This extract may be subjected to decolorization treatment and deodorization treatment by a conventional method as necessary. The oily substance obtained as the extract contains squalene and tocopherols (β as a main component, glycerides mainly composed of saturated and unsaturated fatty acids having 16 to 18 carbon atoms, such as oleic acid, palmitic acid, and stearic acid. -Tocopherol, γ-tocopherol, etc.), sterols (stigmasterol, β-sitosterol, campesterol, spinasterol, avenasterol, etc.), aliphatic alcohols, carotenoids (β-carotene), etc. Does not dissolve.

本発明の発毛促進剤は、前述のノコギリヤシ果実抽出物及びカボチャ種子抽出物を有効成分として含むものであり、両抽出物の比率は任意であるが、ノコギリヤシ果実抽出物/カボチャ種子抽出物(質量基準)が90/10〜10/90の場合に本発明の所望効果が増強され、さらには60/40〜40/60の場合に一層顕著な所望効果が発現される。また、本発明の発毛促進剤は以下に述べるように適宜に種々の添加物質を含有させることができるが、該剤における前記両抽出物の含有量は0.1〜90質量%、より望ましくは0.5〜70質量%、最も望ましくは1〜50質量%である。0.1質量%を下回ると本発明の所望効果が小さくなり、90質量%を超えると実用的な製剤や製品を製造することが困難になる場合があり、さらなる所望効果も期待できない。両抽出物はいずれも常温では液体状であり、その混合物も液状を呈するが、本発明の発毛促進剤を製造するにあたって、公知の賦形剤、結合剤、流動化剤、被覆剤等の添加物質を適宜に用いて粉末状、顆粒状、錠剤状又はカプセル状の形態に加工することも可能である。The hair growth promoter of the present invention contains the aforementioned saw palm fruit extract and pumpkin seed extract as active ingredients, and the ratio of both extracts is arbitrary, but the saw palm fruit extract / pumpkin seed extract ( When the mass basis is 90/10 to 10/90, the desired effect of the present invention is enhanced, and when it is 60/40 to 40/60, a more remarkable desired effect is exhibited. The hair growth promoter of the present invention can appropriately contain various additive substances as described below, but the content of both extracts in the agent is preferably 0.1 to 90% by mass. Is 0.5 to 70% by mass, and most desirably 1 to 50% by mass. If the amount is less than 0.1% by mass, the desired effect of the present invention is reduced. If the amount exceeds 90% by mass, it may be difficult to produce a practical preparation or product, and no further desired effect can be expected. Both extracts are liquid at room temperature, and the mixture is also liquid. However, in producing the hair growth promoter of the present invention, known excipients, binders, fluidizing agents, coating agents, etc. It is also possible to process into a powder, granule, tablet, or capsule form by appropriately using an additive substance.

前記添加物質は目的や用途に応じて常法に従って使用すればよく、賦形剤や結合剤の一例としてグルコース、デキストリン、マンニトール、乳糖、白糖、カゼイン、澱粉又はその加工物、結晶セルロース、セルロースの各種誘導体、ポリビニルアルコール、ポリビニルピロリドン、アラビアガム、アルギン酸等を挙げることができる。流動化剤としてシリカゲル、微粒二酸化ケイ素、アルミノケイ酸ナトリウム、炭酸カルシウム、リン酸カルシウム等、被覆剤としてゼラチン、アルギン酸ナトリウム、カルボキシメチルセルロース等がある。The additive substance may be used in accordance with conventional methods according to the purpose and application. Examples of excipients and binders include glucose, dextrin, mannitol, lactose, sucrose, casein, starch or processed products thereof, crystalline cellulose, and cellulose. Examples include various derivatives, polyvinyl alcohol, polyvinyl pyrrolidone, gum arabic, and alginic acid. Examples of the fluidizing agent include silica gel, fine silicon dioxide, sodium aluminosilicate, calcium carbonate, and calcium phosphate, and examples of the coating agent include gelatin, sodium alginate, carboxymethylcellulose, and the like.

本発明の発毛促進剤においては、ノコギリヤシ果実抽出物及びカボチャ種子抽出物をシクロデキストリンで包接させた形態のものとして用いることが望ましい態様である。両抽出物の各々をシクロデキストリンで包接したものを混合してもよい。この包接物を調製するには常法に準じて行えばよく、例えば、約40℃〜約80℃の加熱水にノコギリヤシ果実抽出物及びカボチャ種子抽出物を加えて懸濁させ、さらに両抽出物の総質量の約3〜約50倍、より好ましくは約4〜20倍、とりわけ約4〜10倍のシクロデキストリンを添加し、混合、冷却後に噴霧乾燥又は凍結乾燥することにより得ることができる。本発明では、ノコギリヤシ果実抽出物及びカボチャ種子抽出物のシクロデキストリン包接物を用いると、水に難溶の両抽出物の水溶化ないしは水分散化、呈味の改善等が可能となることに加えて、両抽出物をそのまま使用する場合に比べて発毛促進効果がより一層増強される点に大きなメリットがある。In the hair growth promoter of the present invention, it is desirable to use a saw palm fruit extract and a pumpkin seed extract in a form of inclusion with cyclodextrin. You may mix what extracted each of both extracts with the cyclodextrin. The clathrate may be prepared according to a conventional method. For example, a saw palm fruit extract and a pumpkin seed extract are added to and suspended in heated water at about 40 ° C. to about 80 ° C. It can be obtained by adding about 3 to about 50 times, more preferably about 4 to 20 times, especially about 4 to 10 times, cyclodextrin, and spray drying or freeze drying after mixing and cooling. . In the present invention, when a cyclodextrin inclusion product of a saw palm fruit extract and a pumpkin seed extract is used, water-soluble or water-dispersed both water-extracted extracts, improvement of taste, etc. can be achieved. In addition, there is a great merit in that the hair growth promoting effect is further enhanced as compared with the case where both extracts are used as they are.

ここで、シクロデキストリンは、α型(シクロヘキサアミロース)、β型(シクロヘプタアミロース)又はγ型(シクロオクタアミロース)のほか、これらの誘導体、すなわち、2,6−ジメチル−β−シクロデキストリン、カルボキシメチル−γ−シクロデキストリン等のメチル化シクロデキストリン、ヒドロキシエチル−β−シクロデキストリン、ヒドロキシプロピル−β−シクロデキストリン等のヒドロキシアルキル化シクロデキストリン、グルコシル化−あるいはマルトシル化−シクロデキストリン、ジアルキルアミノエチル化シクロデキストリン、分枝鎖シクロデキストリン等を用いることも可能である。このうち、コストや汎用性の面からα−又はβ−シクロデキストリンが好ましく、飲料類やドリンク剤等の液体状製品を意図する場合には、ヒドロキシプロピル−β−シクロデキストリン又はメチル−γ−シクロデキストリンが好適である。Here, cyclodextrin is α-type (cyclohexaamylose), β-type (cycloheptaamylose) or γ-type (cyclooctaamylose), and derivatives thereof, that is, 2,6-dimethyl-β-cyclodextrin, Methylated cyclodextrins such as carboxymethyl-γ-cyclodextrin, hydroxyalkyl-β-cyclodextrins, hydroxyalkylated cyclodextrins such as hydroxypropyl-β-cyclodextrin, glucosylated or maltosylated cyclodextrins, dialkylaminoethyl Cyclodextrins, branched cyclodextrins, and the like can also be used. Of these, α- or β-cyclodextrin is preferred from the viewpoints of cost and versatility. When liquid products such as beverages and drinks are intended, hydroxypropyl-β-cyclodextrin or methyl-γ-cyclodextrin is preferred. Dextrin is preferred.

次に、本発明の経口発毛促進剤のさらに望ましい態様は、前記のノコギリヤシ果実抽出物及びカボチャ種子抽出物と血流改善作用のある物質とを有効成分として含有してなることを特徴とするものである。Next, a further desirable embodiment of the oral hair growth-promoting agent of the present invention is characterized by comprising the above saw palm fruit extract and pumpkin seed extract and a substance having an effect of improving blood flow as active ingredients. Is.

ここで、血流改善作用のある物質とは、経口摂取あるいは投与が可能であり、それにより血流・血液循環の改善、血行の促進に有効なものをいう。このような血流改善作用物質としては、例えば、イチョウ葉エキス、紅花抽出物、プラセンタエキス、トウガラシ抽出物、カプサイシン、人参エキス、センブリエキス、フコイダン、ビタミンE及びその誘導体(酢酸トコフェロール等)、パントテン酸及びその塩(カルシウム塩、ナトリウム塩等)、グリチルリチン酸やグリチルレチン酸及びその塩(ナトリウム塩、カリウム塩等)、タヒボエキス、アルギニン及びその誘導体(アルギニングルタマート等)、ニコチン酸及びその誘導体(メチルエステル等)、ローズマリー抽出物、ショウガエキス、ショウガオール、ジンゲロール、ジンゲロン、イソフラボン、ビタミンB、ウコン抽出物、ブドウの種子・葉・茎等の抽出物、ルチン、米胚芽発酵エキス、トウキエキス、ニンニクエキス、サンショウエキス等が知られている。本発明の発毛促進剤では、これらの例示に限定されることなく血流改善作用物質の1種又は2種以上を用いることができる。Here, the substance having an effect of improving blood flow means a substance that can be taken orally or administered and is effective for improving blood flow and blood circulation and promoting blood circulation. Examples of such blood flow improving agents include ginkgo biloba extract, safflower extract, placenta extract, capsicum extract, capsaicin, carrot extract, assembly extract, fucoidan, vitamin E and its derivatives (such as tocopherol acetate), pantothene, and the like. Acids and salts thereof (calcium salts, sodium salts, etc.), glycyrrhizic acid and glycyrrhetinic acid and salts thereof (sodium salts, potassium salts, etc.), tahibo extract, arginine and derivatives thereof (arginine glutamate, etc.), nicotinic acid and derivatives thereof ( Methyl ester, etc.), rosemary extract, ginger extract, gingerol, gingerol, gingerone, isoflavone, vitamin B 3 , turmeric extract, grape seed, leaf, stem extract, rutin, rice germ ferment extract, toki Extract, garlic , Pepper extract, and the like are known. The hair growth promoter of the present invention is not limited to these examples, and one or more of blood flow improving agents can be used.

これに関連して、本発明者らは、本発明の経口発毛促進剤と併用することによって、より一層強力な発毛促進効果を発揮し得る血流改善作用物質をさらに詳細に検討した結果、ツバキの種子の抽出物と緑茶の葉の抽出物が極めて有効であることを見出した。すなわち、本発明の望ましい経口発毛促進剤は、前述のノコギリヤシ果実抽出物及びカボチャ種子抽出物と、血流改善作用のあるツバキ種子抽出物及び/又は緑茶葉抽出物とを有効成分として含有してなることを特徴とするものである。In this connection, the present inventors have examined in further detail a blood flow improving agent capable of exerting a stronger hair growth promoting effect by using in combination with the oral hair growth promoting agent of the present invention. We found that the camellia seed extract and the green tea leaf extract are extremely effective. That is, a desirable oral hair growth promoter of the present invention contains the above-mentioned saw palm fruit extract and pumpkin seed extract, and camellia seed extract and / or green tea leaf extract having an effect of improving blood flow as active ingredients. It is characterized by.

本発明に係るツバキ種子抽出物について以下に詳述する。ツバキはツバキ科(Theaceae)、ツバキ属(Camellia)のツバキ節に属するツバキ(Camelliajaponica)をいい、この例としてヤブツバキ(C.japonica var.japonica)、ユキツバキ(C.japonica subsp.rusticana)、リンゴツバキ(C.japonica var.macrocarpa)、ホウザンツバキ(C.japonica subsp.hozanensis)、ホンコンツバキ(C.hongkongenesis)、トウツバキ(C.reticulata)、サルウィンツバキ(C.saluenensis)、ピタールツバキのピタルディー種(C.pitardii var.pitardii)及びユンナン種(C.pitardii var.yunnanica)、金花茶(C.nitidissima)、ヤマツバキ(ヤブツバキと同種)、山茶花(ヤブツバキと同種)、ヤクシマツバキ(リンゴツバキと同種)等を挙げることができる。これらのツバキは日本列島、朝鮮半島、中国山東半島等で自生し又は栽培されているものを適宜に利用すればよい。The camellia seed extract according to the present invention is described in detail below. Camellia refers to Camellia japonica belonging to the Camellia family, and examples include C. japonica var. Japonica and C. japonic apple. (C. japonica var. Macrocarpa), C. japonica subsp. Hozanensis, C. hongkongenes, C. reticulata, C. isluen p. p. var. pi.) and Yunnan species (C. piard) ii var. yunnanica), gold flower tea (C. nitidisima), Japanese camellia (same kind of Japanese camellia), mountain tea flower (same kind as Japanese camellia), Japanese white camellia (same kind as apple camellia) and the like. What is necessary is just to utilize suitably these camellia which are growing naturally in the Japanese archipelago, the Korean peninsula, the Shandong peninsula of China, etc.

本発明に係るツバキ種子抽出物を製造するためには、前記のツバキの実及び/又は種子を圧搾処理、ヘキサンやヘプタン等の疎水性有機溶媒又は液化二酸化炭素、液化プロパン等の液化ガスを用いた超臨界抽出処理等に供して、常法により油分を抽出して分離した残渣である脱脂物を原料とすることが望ましい。ここで、ツバキの実及び/又は種子は早熟実及び成熟実のいずれでもよく、これらの種子を用いてもよいが、成熟実又はその種子を用いると脱脂物又は/及び有効成分の収量が多くなり望ましい。より好ましくは種子を用いる。好適な態様として、成熟実から得られる種子を1〜2週間程度、天日等で乾燥させたものを用いる。In order to produce the camellia seed extract according to the present invention, the aforementioned camellia fruits and / or seeds are squeezed, a hydrophobic organic solvent such as hexane or heptane, or a liquefied gas such as liquefied carbon dioxide or liquefied propane is used. It is desirable to use a defatted material, which is a residue obtained by extracting and separating oil by a conventional method, using a supercritical extraction treatment or the like. Here, the camellia fruits and / or seeds may be either early-ripening fruits or mature fruits, and these seeds may be used, but when mature fruits or seeds thereof are used, the yield of defatted products and / or active ingredients is high. It is desirable. More preferably seeds are used. As a preferred embodiment, seeds obtained from mature fruits are dried for about 1 to 2 weeks in the sun.

本発明に係るツバキ種子抽出物の活性成分は望ましくは水性成分である。この水性成分は前記脱脂粕を原料として任意の方法で製造することが可能であるが、水及び/又は低級アルコールを用いて抽出処理するのが好ましい。低級アルコールは、その炭素数が大きくなると脱脂粕中の油性物質が抽出される傾向が大きくなるため、炭素数が5程度までのものが望ましく、メタノール、エタノール、ノルマルプロパノール、イソプロパノール、ノルマルブタノール、イソブタノール等を例示できる。炭素数が大きい低級アルコールを使用する場合は、脱脂粕中の油性成分の抽出を抑制するために含水率を高めるのがよい。例えば、プロパノールの場合の含水率は約20質量%〜約50質量%とし、ブタノールの場合の含水率は約40質量%〜約70質量%とする。望ましい抽出溶媒は水、メタノール及びエタノール、及び、これらの含水アルコール(含水率:0〜100質量%)であり、より好適には水又は含水率が50質量%以上の含水メタノールあるいは含水エタノールであり、さらに望ましくは水である。The active component of the camellia seed extract according to the present invention is desirably an aqueous component. The aqueous component can be produced by any method using the defatted koji as a raw material, but is preferably extracted with water and / or a lower alcohol. The lower alcohol has a tendency to extract the oily substance in the defatted soot as the carbon number of the lower alcohol increases. Therefore, those having a carbon number of up to about 5 are desirable, such as methanol, ethanol, normal propanol, isopropanol, normal butanol, isopropanol. Examples include butanol. When using a lower alcohol having a large carbon number, it is preferable to increase the water content in order to suppress the extraction of oily components in the defatted soot. For example, the water content in the case of propanol is about 20% by mass to about 50% by mass, and the water content in the case of butanol is about 40% by mass to about 70% by mass. Desirable extraction solvents are water, methanol and ethanol, and water-containing alcohols thereof (water content: 0 to 100% by mass), more preferably water or water-containing methanol or water-containing ethanol having a water content of 50% by mass or more. More preferably, it is water.

脱脂粕を抽出するには、脱脂粕1質量部に対して前記抽出溶媒を約1〜約30質量倍加え、常圧下又は約1〜約5気圧の加圧下、常温〜約120℃で、約10分〜約3時間、必要に応じて撹拌して混合後、常温に冷却して濾過し、濾液を減圧乾燥、噴霧乾燥、凍結乾燥等の適当な手段により濃縮、乾燥する。この乾燥物は適宜に粉砕処理してもよい。このようにして本発明に係るツバキ種子に含まれる水溶性成分である淡黄色ないし黄赤色の固体を得ることができる。前記抽出方法は、一旦抽出処理した抽出残渣を同様に繰り返し抽出処理したり、約1〜約3気圧の加圧下、約100〜約130℃で行うことによって、本発明に係る水溶性成分の収量を増やすことも可能であり、また、前記抽出物をさらに溶剤分別、イオン交換樹脂、シリカゲル、活性アルミナ等の吸着剤を充填したカラムによる分画、液体クロマトグラフィーによる分取等の公知の手段に供して活性成分を濃縮、精製することもできる。この水溶性成分はサポニン、タンニン等を含む。In order to extract the defatted soot, the extraction solvent is added in an amount of about 1 to about 30 times by mass with respect to 1 part by weight of the defatted soot, at a normal pressure or under a pressure of about 1 to about 5 atm. After stirring and mixing for 10 minutes to about 3 hours as necessary, the mixture is cooled to room temperature and filtered, and the filtrate is concentrated and dried by an appropriate means such as drying under reduced pressure, spray drying or freeze drying. This dried product may be appropriately pulverized. In this way, a light yellow to yellow-red solid that is a water-soluble component contained in camellia seeds according to the present invention can be obtained. In the extraction method, the extraction residue once extracted is similarly repeatedly extracted, or is performed at about 100 to about 130 ° C. under a pressure of about 1 to about 3 atmospheres, whereby the yield of the water-soluble component according to the present invention is obtained. In addition, the extract can be further subjected to known means such as solvent fractionation, fractionation with a column packed with an adsorbent such as ion exchange resin, silica gel, activated alumina, and fractionation by liquid chromatography. It can also be used to concentrate and purify the active ingredient. This water-soluble component includes saponin, tannin and the like.

前記水溶性成分に含まれるサポニンとして、3β−[2−O−β−D−ガラクトピラノシル−3−O−(2−O−β−D−グルコピラノシル−α−L−アラビノピラノシル)−β−D−グルコピラヌロノシルオキシ]オレアナ−12−エン−16α,22α,28−トリオール22−[(Z)−2−メチル−2−ブテノアート]であるカメリアサポニン(Camelliasaponin)A1、3β−[2−O−β−D−ガラクトピラノシル−3−O−(2−O−β−D−グルコピラノシル−α−L−アラビノピラノシル)−β−D−グルコピラヌロノシルオキシ)オレアナ−12−エン−16α,22α,28−トリオール22−[(E)−2−メチル−2−ブテノアート]であるカメリアサポニン(Camelliasaponin)A2、3β−[2−O−β−D−ガラクトピラノシル−3−O−(2−O−β−D−グルコピラノシル−α−L−アラビノピラノシル)−β−D−グルコピラヌロノシルオキシ)−16α,28−ジヒドロキシ−22α−[[(Z)−2−メチル−2−ブテノイル]オキシ]オレアナ−12−エン−23−アールであるカメリアサポニン(Camelliasaponin)B1、3β−[[2−O−β−D−ガラクトピラノシル−3−O−(2−O−β−D−グルコピラノシル−α−L−アラビノピラノシル)−β−D−グルコピラヌロノシル)オキシ]−16α,28−ジヒドロキシ−22α−[[(E)−2−メチル−2−ブテノイル]オキシ]オレアナ−12−エン−23−アールであるカメリアサポニン(Camelliasaponin)B2、3β−[2−O−β−D−ガラクトピラノシル−3−O−(2−O−β−D−グルコピラノシル−α−L−アラビノピラノシル)−β−D−グルコピラヌロノシルオキシ]オレアナ−12−エン−16α,22α,23,28−テトラオール22−[(Z)−2−メチル−2−ブテノアート]であるカメリアサポニン(Camelliasaponin)C1、及び、3β−[2−O−β−D−ガラクトピラノシル−3−O−(2−O−β−D−グルコピラノシル−α−L−アラビノピラノシル)−β−D−グルコピラヌロノシルオキシ]オレアナ−12−エン−16α,22α,23,28−テトラオール22−[(E)−2−メチル−2−ブテノアート]であるカメリアサポニン(Camelliasaponin)C2等を例示することができる。これらのサポニン類はツバキに特異的に含まれている。As a saponin contained in the water-soluble component, 3β- [2-O-β-D-galactopyranosyl-3-O- (2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl) ) -Β-D-glucopyranuronosyloxy] oleana-12-ene-16α, 22α, 28-triol 22-[(Z) -2-methyl-2-butenoate] Camellia saponin A1, 3β- [2-O-β-D-galactopyranosyl-3-O- (2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl) -β-D-glucopyranurono Camellia saponin A2, 3β which is (siloxy) oleana-12-ene-16α, 22α, 28-triol 22-[(E) -2-methyl-2-butenoate] [2-O-β-D-galactopyranosyl-3-O- (2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl) -β-D-glucopyranuronosyloxy ) -16α, 28-dihydroxy-22α-[[(Z) -2-methyl-2-butenoyl] oxy] oleana-12-en-23-al, Camellia saponin B1, 3β-[[2- O-β-D-galactopyranosyl-3-O- (2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl) -β-D-glucopyranuronosyl) oxy]- Camellia saponin B2, 3β which is 16α, 28-dihydroxy-22α-[[((E) -2-methyl-2-butenoyl] oxy] oleana-12-en-23-al [2-O-β-D-galactopyranosyl-3-O- (2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl) -β-D-glucopyranuronosyloxy Oleana-12-ene-16α, 22α, 23,28-tetraol 22-[(Z) -2-methyl-2-butenoate], Camellia saponin C1, and 3β- [2-O-] [beta] -D-galactopyranosyl-3-O- (2-O- [beta] -D-glucopyranosyl- [alpha] -L-arabinopyranosyl)-[beta] -D-glucopyranuronosyloxy] oleana-12 Examples include Camellia saponin C2, which is ene-16α, 22α, 23,28-tetraol 22-[(E) -2-methyl-2-butenoate]. These saponins are specifically contained in camellia.

また、本発明に係る緑茶葉抽出物について以下に説明する。茶は茶の木(チャノキ)、茶樹ともよばれ、ツバキ科(Theaceae)、ツバキ属(Camellia)のチャ節に属する常緑樹である(学名:Camellia sinensis)。日本や中国で栽培されている低木の中国種(C.sinensis var.sinensis)とインドやスリランカで栽培されている高木のアッサム種(C.sinensis var.assamica)がある。通常は、これらから摘み取った茶葉に蒸煮・釜炒り等の加熱処理を施して葉に含まれる酵素を失活させたものを不発酵茶(これを一般に緑茶という)として、また、前記加熱処理後に微生物発酵させたものを後発酵茶(黒茶)として、それぞれ飲食に利用している。Moreover, the green tea leaf extract which concerns on this invention is demonstrated below. Tea is also called a tea tree or tea tree, and is an evergreen tree belonging to the tea section of the family Camellia (Scientific name: Camellia sinensis). There are Chinese species (C. sinensis var. Sinensis) cultivated in Japan and China and Assam species (C. sinensis var. Assamica) cultivated in India and Sri Lanka. Usually, the tea leaves picked from these are subjected to heat treatment such as steaming and cooking in a kettle to inactivate the enzyme contained in the leaves as non-fermented tea (this is generally called green tea), and after the heat treatment What was microbially fermented is used as a post-fermented tea (black tea) for food and drink.

本発明に係る緑茶葉抽出物を製造するには公知の溶剤抽出法、超臨界炭酸ガス溶媒抽出法等を利用することができ、例えば、前記茶葉の生葉若しくは乾燥葉を適宜に細断又は粉砕し、水及び/又は低級アルコールを抽出溶媒として、茶葉1質量部に対して抽出溶媒を約1〜約50質量部加えて、常温〜約90℃、常圧下又は約1〜約5気圧の加圧下で、約10分〜約10時間、必要に応じて攪拌して混合した後、常温まで冷却して濾過し、濾液を減圧乾燥、噴霧乾燥、凍結乾燥等の適当な処理に供して濃縮、乾燥する。このようにして本発明に係る、黄色〜褐色で固体(粉末)状の緑茶葉抽出物を得ることができる。In order to produce the green tea leaf extract according to the present invention, a known solvent extraction method, a supercritical carbon dioxide gas solvent extraction method, or the like can be used. For example, the green leaf or the dried leaf of the tea leaf is appropriately shredded or ground. Then, using water and / or lower alcohol as an extraction solvent, about 1 to about 50 parts by mass of the extraction solvent is added to 1 part by mass of tea leaves, and normal temperature to about 90 ° C. under normal pressure or about 1 to about 5 atmospheres Under pressure, the mixture is stirred for about 10 minutes to about 10 hours, if necessary, then cooled to room temperature and filtered, and the filtrate is subjected to an appropriate treatment such as vacuum drying, spray drying, freeze drying, and the like. dry. In this way, a yellow to brown and solid (powder) green tea leaf extract according to the present invention can be obtained.

ここで、低級アルコールはメタノール、エタノール、ノルマルプロパノール、イソプロパノール、ブタノール等の炭素数が5程度までの1価アルコールが望ましく、さらには水、含水メタノール又は含水エタノールがより望ましく、水又は含水率が約50質量%以下の含水エタノールが最も好適である。また、前記抽出工程において、一旦抽出処理した抽出残渣を同様に繰り返し抽出したり、約1〜約3気圧程度の加圧下、約100〜約130℃で抽出処理することにより、本発明に係る緑茶葉抽出物の活性成分の増収が可能となる。なお、前記抽出物をさらに溶剤分別したり、イオン交換樹脂、シリカゲル、活性アルミナ、官能基架橋ポリマー等の吸着剤による分画、高速液体クロマトグラフィーによる分取等の公知手段で処理することにより活性成分を濃縮、高純度精製してもよい。Here, the lower alcohol is preferably a monohydric alcohol having up to about 5 carbon atoms such as methanol, ethanol, normal propanol, isopropanol, butanol, and more preferably water, water-containing methanol or water-containing ethanol, and water or water content is about Most preferred is 50% by weight or less hydrous ethanol. Further, in the extraction step, the extraction residue once extracted is similarly repeatedly extracted, or extracted at about 100 to about 130 ° C. under a pressure of about 1 to about 3 atmospheres, whereby the green tea according to the present invention. Increased yield of active ingredients in leaf extract. The extract can be activated by further solvent fractionation, or by treatment by known means such as fractionation with an adsorbent such as ion exchange resin, silica gel, activated alumina, functional group cross-linked polymer, or fractionation by high performance liquid chromatography. The components may be concentrated and purified with high purity.

本発明に係る緑茶葉抽出物はカテキン類を主成分として、テアニン、γ−アミノ酪酸、サポニン類、ビタミン類(ビタミンB、C、E、β−カロテン等)、ミネラル類(例えば、カリウム、カルシウム、リン、マンガン)等を含む。カテキン類はカテキン、エピガロカテキンガレート、エピカテキン、エピカテキンガレート、カテキンガレート等である。The green tea leaf extract according to the present invention is mainly composed of catechins, theanine, γ-aminobutyric acid, saponins, vitamins (vitamin B 2 , C, E, β-carotene, etc.), minerals (for example, potassium, Calcium, phosphorus, manganese) and the like. The catechins are catechin, epigallocatechin gallate, epicatechin, epicatechin gallate, catechin gallate and the like.

本発明の経口発毛促進剤において、ノコギリヤシ果実抽出物及びカボチャ種子抽出物と併用する血流改善作用物質の含有量は該剤全体の0.01〜45質量%であり、望ましくは0.1〜40質量%であり、さらに望ましくは0.5〜30質量%である。0.01質量%を下回ると併用による効果が小さく、逆に45質量%を超える使用も更なる所望効果は期待できない。なお、本発明の経口発毛促進剤では、血流改善作用物質の含有量はノコギリヤシ果実抽出物及びカボチャ種子抽出物の合計量を超えないものが望ましい。また、血流改善作用物質は前述の公知の物質や抽出物を単独又は複数で任意に用いることができるが、望ましいものはツバキ種子抽出物及び/又は緑茶葉抽出物であり、さらに望ましいものはツバキ種子抽出物である。そして、このツバキ種子抽出物はツバキ種子の脱脂物から水及び又は低級アルコールで抽出される水溶性成分を含有するものであり、ツバキ特有のサポニン類を含むものであることが好適な態様である。ツバキ種子抽出物と緑茶葉抽出物とを併用する場合の比率(質量基準)は、ツバキ種子抽出物/緑茶葉抽出物が99/1〜40/60、より好ましくは90/10〜50/50である。In the oral hair growth-promoting agent of the present invention, the content of the blood flow improving agent used in combination with the saw palm fruit extract and the pumpkin seed extract is 0.01 to 45% by mass, preferably 0.1%. It is -40 mass%, More preferably, it is 0.5-30 mass%. If the amount is less than 0.01% by mass, the effect of the combined use is small, and conversely the use exceeding 45% by mass cannot be expected to have further desired effects. In addition, in the oral hair growth promoter of this invention, it is desirable that the content of the blood flow improving agent does not exceed the total amount of the saw palm fruit extract and the pumpkin seed extract. Further, as the blood flow improving agent, the above-mentioned known substances and extracts can be arbitrarily used alone or in combination, but desirable ones are camellia seed extract and / or green tea leaf extract, and more desirable ones are Camellia seed extract. And this camellia seed extract contains the water-soluble component extracted with the water and / or a lower alcohol from the defatted thing of a camellia seed, and it is a suitable aspect that it contains the saponins peculiar to a camellia. When the camellia seed extract and the green tea leaf extract are used in combination, the ratio (mass basis) of the camellia seed extract / green tea leaf extract is 99/1 to 40/60, more preferably 90/10 to 50/50. It is.

前述の経口発毛促進剤は、ノコギリヤシ果実抽出物及びカボチャ種子抽出物、より望ましくは、これら両抽出物と血流改善作用物質とりわけツバキ種子抽出物及び/又は緑茶葉抽出物との併用物を有効成分として、これをそのまま、すなわち、前記有効成分のみからなる粉末状、固形状、ペースト状又は液体状の形態となし、これを飲食品、医薬品、医薬部外品、飼料等の用途に利用することが可能である。本発明の経口発毛促進剤は、また、これが利用され得る前記用途における公知の添加物を適宜に併用して、常法により含有せしめて経口用組成物として利用することもできる。ここで、公知の添加物は経口摂取するために通常利用されるものでよく、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、湿潤剤、流動化剤、保存剤、界面活性剤、安定剤、希釈剤、溶解剤、等張化剤、殺菌剤、防腐剤、矯味剤、矯臭剤、着色剤、香料等の添加物質を使用できる。さらには、前記の先行技術文献に記載のものに限定されることなく、発毛・育毛・養毛等の作用を有する既知成分やその含有素材を併用してもよい。本発明の経口発毛促進剤は、さらに、飲食品、医薬品、医薬部外品、飼料、その他の産業分野の各種製品の配合原料の一部として使用することもできる。とりわけ、発毛促進、育毛、養毛、脱毛あるいは薄毛の予防や改善等のための製品となすことが好ましい。The aforementioned oral hair growth promoter comprises a combination of a saw palm fruit extract and a pumpkin seed extract, and more preferably a combination of both these extracts with a blood flow improving agent, particularly a camellia seed extract and / or a green tea leaf extract. As an active ingredient, it is used as it is, that is, in the form of powder, solid, paste or liquid consisting only of the active ingredient, and this is used for applications such as foods and drinks, pharmaceuticals, quasi drugs, and feeds. Is possible. The oral hair growth-promoting agent of the present invention can also be used as an oral composition by appropriately combining well-known additives for the above-mentioned uses for which it can be utilized and containing them by conventional methods. Here, known additives may be those usually used for ingestion, for example, excipients, binders, disintegrants, lubricants, wetting agents, fluidizing agents, preservatives, surfactants. Additives such as stabilizers, diluents, solubilizers, tonicity agents, bactericides, preservatives, flavoring agents, flavoring agents, coloring agents, and fragrances can be used. Furthermore, it is not limited to the thing described in the said prior art document, You may use together the known component which has effects, such as hair growth, hair growth, and hair restoration, and its containing material. The oral hair growth promoter of the present invention can also be used as a part of a blended raw material for foods and drinks, pharmaceuticals, quasi drugs, feeds, and other various industrial products. In particular, it is preferable to provide a product for promoting hair growth, hair growth, hair nourishing, hair loss or preventing or improving thinning hair.

本発明の経口発毛促進剤を公知の添加物と併用して経口用組成物とする場合の形態は、粉末剤、顆粒剤、錠剤、カプセル剤、液剤等のタイプの経口用製剤となすことが可能である。かかる経口用組成物における前記有効成分の含有量は、併用する原料の種類や含有量等により一律に規定し難いが、概ね0.01〜90質量%程度、より望ましくは約0.1〜約70質量%である。前記含有量が約0.01質量%を下回ると本発明の所望効果が認められなくなり、また、本発明の所望効果を発揮させるために多量摂取しなければならず、約90質量%を超えると実用的な製剤組成物を調製することが難しくなる。本発明の発毛促進剤は、これを経口的に摂取又は投与する方法で利用する。この場合の本発明の経口発毛促進剤の好適な摂取量又は投与量の目安は、該剤に含まれる前記有効成分ベースで、ヒト成人(体重50kg)1日あたり約10mg〜約1,000mg、望ましくは約30mg〜約500mg、更に望ましくは約50mg〜約300mgである。When the oral hair growth promoter of the present invention is used in combination with known additives to form an oral composition, it should be an oral preparation of the type such as powder, granule, tablet, capsule, liquid, etc. Is possible. The content of the active ingredient in such an oral composition is difficult to define uniformly depending on the type and content of the raw materials used together, but is generally about 0.01 to 90% by mass, more preferably about 0.1 to about 70% by mass. When the content is less than about 0.01% by mass, the desired effect of the present invention is not recognized, and in order to exert the desired effect of the present invention, a large amount must be ingested. It becomes difficult to prepare a practical pharmaceutical composition. The hair growth-promoting agent of the present invention is used in a method of taking or administering it orally. In this case, a suitable intake or dosage of the oral hair growth-promoting agent of the present invention is about 10 mg to about 1,000 mg per day for a human adult (body weight 50 kg) based on the active ingredient contained in the agent. Preferably about 30 mg to about 500 mg, more preferably about 50 mg to about 300 mg.

本発明の経口発毛促進剤は、これを飲食品、医薬品、医薬部外品、飼料等の公知の製品の配合原料の一部として利用することができる。実用的な製品の例を以下に述べるが、本発明はこの例示により何ら制限されるものではない。The oral hair growth promoter of the present invention can be used as a part of a blended raw material of known products such as foods and drinks, pharmaceuticals, quasi drugs, and feeds. Examples of practical products are described below, but the present invention is not limited to these exemplifications.

飲食品の具体例として、野菜ジュース、果汁飲料、清涼飲料、茶等の飲料類、即席麺、スープ、ゼリー、プリン、ヨーグルト、ケーキプレミックス製品、菓子類、ふりかけ、味噌、醤油、ソース、ドレッシング、マヨネーズ、植物性クリーム、焼肉用たれや麺つゆ等の調味料、麺類、うどん、蕎麦、スパゲッティ、ハムやソーセージ等の畜肉魚肉加工食品、ハンバーグ、コロッケ、ふりかけ、佃煮、ジャム、牛乳、クリーム、バター、スプレッドやチーズ等の粉末状、固形状又は液状の乳製品、マーガリン、パン、ケーキ、クッキー、チョコレート、キャンディー、グミ、ガム等の各種一般加工食品のほか、粉末状、顆粒状、丸剤状、錠剤状、ソフトカプセル状、ハードカプセル状、ペースト状又は液体状の栄養補助食品、特定保健用食品、機能性食品、健康食品、濃厚流動食や嚥下障害用食品の治療食等を挙げることができる。Specific examples of food and drink include beverages such as vegetable juice, fruit juice drinks, soft drinks, tea, instant noodles, soup, jelly, pudding, yogurt, cake premix products, confectionery, sprinkles, miso, soy sauce, sauce, dressing , Mayonnaise, vegetable cream, seasonings such as grilled meat sauce and noodle soup, noodles, udon, soba noodles, spaghetti, processed meat and fish products such as ham and sausage, hamburger, croquette, sprinkle, boiled, jam, milk, cream, Various processed foods such as butter, spread and cheese, powdered, solid or liquid dairy products, margarine, bread, cake, cookies, chocolate, candy, gummi, gum, etc., powder, granules, pills , Tablet, soft capsule, hard capsule, paste or liquid dietary supplement, food for specified health use, Potential food, mention may be made of health food products, the concentrated liquid diet and dysphagia for food diet and the like.

これらの飲食品を製造するには、本発明の発毛促進剤と公知の原材料を用い、あるいは公知の原材料の一部を本発明の発毛促進剤で置き換え、常法によって製造すればよい。例えば、本発明の発毛促進剤を、必要に応じてグルコース、ブドウ糖、デキストリン、乳糖、澱粉又はその加工物、セルロース粉末等の賦形剤、ビタミン類、ミネラル類、動植物や魚介類の油脂、たん白(動植物や酵母由来の蛋白質、その加水分解物等を含む)、糖質、色素、香料、酸化防止剤、界面活性剤、その他の食用添加物、各種栄養機能成分を含む粉末やエキス類等の食用素材とともに混合して粉末、顆粒、ペレット、錠剤等の形状に加工したり、常法により前記例の一般加工食品の形態に加工したり、混合した粉末や液状物をゼラチン、アルギン酸ナトリウム、カルボキシメチルセルロース等の被覆剤で被覆してカプセルに成形したり、飲料(ドリンク類)の形態に加工して、栄養補助食品や健康食品として利用することは好適である。とくに錠剤、カプセル剤やドリンク剤の形態が望ましい。なお、これらの飲食品に含まれる本発明の発毛促進剤の含量や摂取量は、前述の経口用組成物の場合とほぼ同様である。In order to produce these foods and drinks, the hair growth promoter of the present invention and known raw materials may be used, or a part of the known raw materials may be replaced with the hair growth promoter of the present invention and produced by conventional methods. For example, the hair growth-promoting agent of the present invention, if necessary, glucose, glucose, dextrin, lactose, starch or processed product thereof, excipients such as cellulose powder, vitamins, minerals, fats and oils of animals and plants and seafood, Proteins (including proteins from plants and animals, including hydrolysates thereof), carbohydrates, pigments, fragrances, antioxidants, surfactants, other edible additives, powders and extracts containing various nutritional functional ingredients And mixed with edible ingredients such as powders, granules, pellets, tablets, etc., processed into the general processed food form of the above example by conventional methods, and mixed powders and liquids into gelatin and sodium alginate It is suitable to use as a dietary supplement or health food by coating with a coating agent such as carboxymethylcellulose, forming into a capsule, or processing into a beverage (drink) form. That. In particular, tablets, capsules and drinks are desirable. In addition, the content and intake of the hair growth promoter of the present invention contained in these foods and drinks are almost the same as in the case of the aforementioned oral composition.

本発明の発毛促進剤を用いる医薬品は、前記の経口発毛促進剤に本発明の趣旨に反しない範囲で薬学的に許容される公知の賦形剤や添加物を適宜に加え、常法により加工して錠剤、カプセル剤、顆粒剤、散剤、液剤等の製剤となすことができる。これを経口投与して、薄毛、抜け毛、円形脱毛症、男性型脱毛症(AGA)、びまん性脱毛症、分娩後脱毛症等の予防又は治療のために適用する。なお、これらの医薬品に含まれる本発明の発毛促進剤の含量や摂取量は、前述の経口用組成物の場合に準ずる。The pharmaceutical agent using the hair growth promoter of the present invention is prepared by appropriately adding known excipients and additives that are pharmaceutically acceptable within the range not departing from the gist of the present invention to the above oral hair growth promoter. Can be processed into preparations such as tablets, capsules, granules, powders, and liquids. It is administered orally and applied for the prevention or treatment of hair loss, hair loss, alopecia areata, androgenetic alopecia (AGA), diffuse alopecia, postpartum alopecia and the like. In addition, the content and intake of the hair growth promoter of the present invention contained in these pharmaceutical products are the same as those in the aforementioned oral composition.

また、本発明の発毛促進剤をペットフードや家畜用飼料に適用するには、前記飲食品の場合と同様に、公知の各種飼料や飲用水に配合したり、公知の原材料、添加物とともに錠剤状、顆粒状、カプセル状等の製剤形態のものに加工することができる。これらの飼料における本発明の発毛促進剤の含量や摂取量は前述の経口用組成物の場合とほぼ同様である。In addition, in order to apply the hair growth promoter of the present invention to pet food and livestock feed, it is blended in various known feeds and drinking water, as well as known raw materials and additives, as in the case of the food and drink. It can be processed into a pharmaceutical form such as tablet, granule, capsule. The content and intake of the hair growth promoter of the present invention in these feeds are almost the same as in the case of the aforementioned oral composition.

以下の各例において、%、部及び比率はとくにことわらないかぎり質量基準である。In the following examples,%, part and ratio are based on mass unless otherwise specified.

製造例1(ノコギリヤシ果実抽出物)
ノコギリヤシの乾燥果実10kgを粗粉砕し、超臨界流体抽出法(二酸化炭素、40〜45℃、20±3MPa)により油状のノコギリヤシ果実抽出物(試料1とする)1.8kgを得た。この抽出物の組成(GLC分析)は脂肪酸類(ラウリン酸及びオレイン酸を主成分とする炭素数6〜18の飽和及び不飽和脂肪酸):94.8%、脂肪族アルコール類(ヘキサコサノール、オクタコサノール等):0.2%、ステロール類(β−シトステロール、カンペステロール、スチグマステロール):0.3%等であった。
Production Example 1 (Saw palm fruit extract)
10 kg of dried dried palm fruit was coarsely pulverized, and 1.8 kg of an oily saw palm fruit extract (sample 1) was obtained by a supercritical fluid extraction method (carbon dioxide, 40 to 45 ° C., 20 ± 3 MPa). The composition (GLC analysis) of this extract was fatty acids (saturated and unsaturated fatty acids having 6 to 18 carbon atoms mainly composed of lauric acid and oleic acid): 94.8%, aliphatic alcohols (hexacosanol, Octacosanol and the like): 0.2%, sterols (β-sitosterol, campesterol, stigmasterol): 0.3% and the like.

製造例2(カボチャ種子抽出物)
ペポカボチャ(Cucurbita melopepo L.)の乾燥種子10kgを粗粉砕し、製造例1と同様に超臨界流体抽出法により処理して油状のカボチャ種子抽出物(試料2とする)1.9kgを得た。この抽出物の脂質組成はグリセリド類(リノール酸及びオレイン酸を主成分とする炭素数14〜18の飽和及び不飽和脂肪酸のグリセリド):87.5%、スクアレン:0.6%、脂肪族アルコール類:0.1%(ヘキサコサノール、オクタコサノール等)、ステロール類(β−シトステロール、スチグマステロール、アベナステロール等):0.4%、トコフェロール類(β−及びγ−トコフェロール等):0.1%、微量のβ−カロテン等であった。
Production Example 2 (Pumpkin seed extract)
10 kg of dried seeds of pepo pumpkin (Cucurbita melopepo L.) were coarsely pulverized and treated by the supercritical fluid extraction method in the same manner as in Production Example 1 to obtain 1.9 kg of oily pumpkin seed extract (referred to as sample 2). The lipid composition of this extract is glycerides (glycerides of saturated and unsaturated fatty acids having 14 to 18 carbon atoms mainly composed of linoleic acid and oleic acid): 87.5%, squalene: 0.6%, aliphatic alcohol Class: 0.1% (hexacosanol, octacosanol, etc.), sterols (β-sitosterol, stigmasterol, avenasterol, etc.): 0.4%, tocopherols (β- and γ-tocopherol, etc.): 0. 1%, trace amount of β-carotene and the like.

製造例3(シクロデキストリン包接物)
製造例1に記載のノコギリヤシ果実抽出物、製造例2に記載のカボチャ種子抽出物及びβ−シクロデキストリンの割合(質量比)を1:1:8として、常法により前記抽出物のシクロデキストリン包接物(試料3とする)を調製した。
Production Example 3 (cyclodextrin inclusion product)
The ratio of the saw palm fruit extract described in Production Example 1 to the pumpkin seed extract described in Production Example 2 and β-cyclodextrin (mass ratio) was 1: 1: 8. An inclusion product (referred to as sample 3) was prepared.

製造例4(ツバキ種子抽出物(1))
長崎県五島産ヤブツバキの乾燥種子を粗粉砕して蒸煮後、圧搾して圧搾油を分離した圧搾粕を得た。次いで圧搾粕にノルマルヘキサンを加えて常法により抽出処理し、抽出液を分離して抽出粕を採取した。この抽出粕をノルマルヘキサンで洗浄して油分を取り除き脱脂物を採取した。この脱脂物1kgに水3Lを加え、常圧下、85℃に加熱して1時間適宜に撹拌した後、室温まで冷却し、濾過して濾液を分離した。この濾過残渣に再度水200mLを加えて同様に加熱、攪拌、冷却後、濾過して濾液を採取した。両濾液を合わせて減圧下に濃縮し、凍結乾燥及び粉砕して、水溶性成分からなる粉末状のツバキ種子抽出物(試料4とする)185gを得た。この抽出物は、これを常法により加水分解してHPLC分析したところ、サポニンのアグリコンであるサポゲニンを17.8%、フラボノールの一種であるケンフェロールを2.7%含むものであった。
Production Example 4 (Camellia seed extract (1))
The dried seeds of Yabu camellia from Goto, Nagasaki Prefecture were coarsely pulverized and steamed, and then pressed to obtain a pressed rice cake from which compressed oil was separated. Next, normal hexane was added to the press koji and extraction was performed by a conventional method. The extract was separated and the extract koji was collected. The extract was washed with normal hexane to remove the oil, and a defatted material was collected. 3 kg of water was added to 1 kg of the defatted material, heated to 85 ° C. under normal pressure and stirred appropriately for 1 hour, cooled to room temperature, and filtered to separate the filtrate. 200 mL of water was again added to the filtration residue, and the mixture was heated, stirred and cooled in the same manner, and then filtered to collect a filtrate. Both filtrates were combined, concentrated under reduced pressure, lyophilized and pulverized to obtain 185 g of powdered camellia seed extract (referred to as sample 4) consisting of water-soluble components. This extract was hydrolyzed by a conventional method and analyzed by HPLC. As a result, it contained 17.8% sapogenin which is an aglycone of saponin and 2.7% kaempferol which is a kind of flavonol.

製造例5(ツバキ種子抽出物(2))
製造例4に記載の方法で得た脱脂物1kgに含水エタノール(含水率35%)2Lを加え、80℃で1時間加熱還流した後、室温まで冷却し、濾過して濾液を分離した。この濾過残渣に再度含水エタノール(含水率35%)2Lを加えて同様に加熱し、冷却後、濾過して濾液を採取した。両濾液を合わせて減圧下に濃縮し、凍結乾燥及び粉砕して、水溶性成分を含む粉末(試料5とする)13.3gを得た。該粉末を製造例4と同様に加水分解してHPLC分析した結果、サポゲニン含量は13.1%であり、ケンフェロール含量は2.3%であった。
Production Example 5 (Camellia seed extract (2))
2 kg of water-containing ethanol (water content 35%) was added to 1 kg of the defatted product obtained by the method described in Production Example 4, and the mixture was heated to reflux at 80 ° C. for 1 hour, cooled to room temperature, and filtered to separate the filtrate. To this filtration residue, 2 L of water-containing ethanol (water content 35%) was added again and heated in the same manner. After cooling, the filtrate was collected by filtration. Both filtrates were combined, concentrated under reduced pressure, lyophilized and pulverized to obtain 13.3 g of a powder containing water-soluble components (sample 5). The powder was hydrolyzed in the same manner as in Production Example 4 and analyzed by HPLC. As a result, the sapogenin content was 13.1% and the kaempferol content was 2.3%.

製造例6(緑茶葉抽出物)
静岡県産の緑茶の乾燥葉1kgを粗細断し、水3Lを加えて、常圧下、85℃に加熱して20分間適宜に撹拌した後、室温まで冷却し、濾過して濾液を分離した。この濾過残渣に再度水2Lを加えて同様に加熱し、攪拌、冷却後、濾過して濾液を採取した。両濾液を合わせて減圧下に濃縮した。その濃縮溶液を、合成吸着剤のダイヤイオン(登録商標)HP−20(三菱化学(株)製)を充填したカラムクロマトグラフィーに供した。水5Lを通液して洗浄した後、含水エタノール(含水率30%)5Lを通液し、該含水エタノールに可溶の溶液を回収した。この溶液を減圧下に濃縮し、噴霧乾燥及び粉砕して、粉末状の緑茶葉抽出物(試料6とする)25gを得た。該粉末をHPLC分析した結果、カテキン類(エピガロカテキンガレートを主成分とし、ガロカテキンガレート、エピカテキンガレート、エピガロカテキン、カテキン、エピカテキン等)の含量は90.2%、カフェイン:0.1%等であった。
Production Example 6 (Green tea leaf extract)
1 kg of dried leaves of green tea produced in Shizuoka Prefecture was roughly chopped, added with 3 L of water, heated to 85 ° C. under normal pressure and stirred for 20 minutes as appropriate, then cooled to room temperature and filtered to separate the filtrate. 2 L of water was again added to the filtration residue and heated in the same manner. After stirring and cooling, the filtrate was collected by filtration. Both filtrates were combined and concentrated under reduced pressure. The concentrated solution was subjected to column chromatography packed with a synthetic adsorbent Diaion (registered trademark) HP-20 (manufactured by Mitsubishi Chemical Corporation). After washing by passing 5 L of water, 5 L of water-containing ethanol (water content 30%) was passed through to recover a solution soluble in the water-containing ethanol. This solution was concentrated under reduced pressure, spray-dried and pulverized to obtain 25 g of a powdery green tea leaf extract (referred to as sample 6). As a result of HPLC analysis of the powder, the content of catechins (including epigallocatechin gallate as a main component, gallocatechin gallate, epicatechin gallate, epigallocatechin, catechin, epicatechin, etc.) was 90.2%, caffeine: 0 1% etc.

試験例1(血流改善作用)
以下に述べる試験に参加することに同意が得られた被験者30名(24〜65歳、男性15名、女性15名)を1群5名に群分けして二重盲検法により血流測定試験を行った。まず、被験者を温度24±2℃、湿度50±10%に制御した恒温・恒湿の部屋に入室させ、10分間安静に待機させた。この後、試験試料を摂取する前の手の甲及び頭皮の血流量をレーザードップラー(Perimed社製、PeriScan PIM II)を用いて測定した。次に、対照群(プラセボ群)には、被験者が色で判別できないように着色したハードカプセル(ゼラチン製。以下同様)にデキストリンを充填したものを、その他の群には、前記同様に着色したハードカプセルに各試験試料を充填したものをそれぞれ水100mLとともに摂取してもらい、30分後、60分後に再び前記と同様に手の甲及び頭皮の血流量を測定した。なお、試験試料は、前記のツバキ種子抽出物(試料4、試料5)、緑茶葉抽出物(試料6)、市販のイチョウ葉抽出物(ビーエイチエヌ(株)製)、ドコサヘキサエン酸含有魚油(クローダジャパン(株)製、DHA含有油脂)とした。
Test example 1 (blood flow improving effect)
30 subjects (24-65 years old, 15 men, 15 women) who agreed to participate in the study described below were divided into 5 groups per group, and blood flow was measured by the double blind method. A test was conducted. First, the subject entered a room of constant temperature and humidity controlled at a temperature of 24 ± 2 ° C. and a humidity of 50 ± 10%, and was allowed to stand quietly for 10 minutes. Thereafter, blood flow in the back and scalp of the hand before taking the test sample was measured using a laser Doppler (Periscan PIM II, manufactured by Perimed). Next, in the control group (placebo group), hard capsules (made of gelatin; the same applies hereinafter) filled with dextrin so that the subject cannot distinguish by color, and in the other groups, hard capsules colored as described above. Each sample filled with each test sample was ingested together with 100 mL of water, and after 30 minutes and 60 minutes, blood flow in the back of the hand and scalp was measured again in the same manner as described above. The test samples were the above camellia seed extract (sample 4, sample 5), green tea leaf extract (sample 6), commercially available ginkgo biloba extract (manufactured by BN Co., Ltd.), docosahexaenoic acid-containing fish oil (Croda Japan) Co., Ltd., DHA-containing fat / oil).

この結果を表1に示す。同表において、数値はプラセボ及び被験物質を摂取する前の値を100としたときの相対値として、平均値±標準偏差で表わした(n=5、ANOVA解析)。表1のデータから、プラセボを摂取した被験者の手の甲及び頭皮の血流量には有意な変化は認められなかったが、試料4や試料5(ツバキ種子抽出物)を摂取した場合は、血流促進作用が公知のイチョウ葉抽出物やドコサヘキサエン酸含有油脂を摂取した場合と同程度に、摂取30分後及び60分後の両時間ともに、手の甲及び頭皮の血流量の値が有意に高かった。又、試料6(緑茶葉抽出物)を摂取した場合は、摂取30分後は血流量に有意な差は認められなかったが、摂取60分後においてはプラセボ群と比べて手の甲及び頭皮の血流量の値が有意に高かった。The results are shown in Table 1. In the same table, the numerical values are expressed as average values ± standard deviation (n = 5, ANOVA analysis) as relative values when the value before taking the placebo and the test substance is 100. From the data in Table 1, there was no significant change in blood flow in the back and scalp of the subjects who took placebo, but blood flow was promoted when samples 4 and 5 (camellia seed extract) were ingested. The values of blood flow in the back of the hand and scalp were significantly higher at both 30 minutes and 60 minutes after ingestion, as in the case of ingesting ginkgo biloba extract and docosahexaenoic acid-containing fats and oils with known effects. In addition, when sample 6 (green tea leaf extract) was ingested, no significant difference was observed in blood flow after 30 minutes of ingestion, but after 60 minutes of ingestion, blood on the back and scalp of the hand compared to the placebo group. The flow value was significantly higher.

Figure 2011105695
Figure 2011105695

試験例2(発毛作用)
以下の試験に参加することに同意が得られた40〜65歳の頭頂部の毛髪が薄い78名(男性:40名、女性:38名)を被験者として、1群6名に群分けして、二重盲検法により試験を行った。対照群には被験者が判別できないように着色したハードカプセルにデキストリンを充填したものを、その他の群には同様に着色したハードカプセルにそれぞれの試料を300mg充填したものを毎日1個、6ヵ月間経口摂取させ、毛髪本数、毛髪成長速度及び毛髪径に及ぼす影響を次の方法により評価した。すなわち、毛髪本数は、デジタルマイクロスコープ((株)ハイロックス製、KH−3000)を用いて頭頂部の所定部位の拡大写真を撮影した後、1cmあたりの毛髪数を測定した。毛髪成長速度は、まず、試験最終日より3日前に頭頂部の所定部位を毛刈りし、前記デジタルマイクロスコープにて拡大写真を撮影し、毛髪の長さを解析した。次に、毛刈りから72時間後の毛の長さを上記同様の方法で測定した。72時間で伸長した毛髪の長さを24時間あたりに換算し、これを毛髪成長速度(μm/24hr)とした。又、毛髪径は、所定部位の毛刈りを行った後、刈りとった毛髪を上記と同様に拡大写真を撮影し、毛髪の太さを解析した。尚、これらの測定はプラセボ及びそれぞれの試料を摂取させる前と、6ヵ月間摂取させた後に実施した。
Test Example 2 (hair growth action)
78 subjects with 40-65 year old parietal hair whose consent was obtained to participate in the following study (male: 40, female: 38) were divided into 6 groups per group. The test was conducted by the double blind method. In the control group, a hard capsule colored so that the subject could not be identified was filled with dextrin, and in the other groups, each of the same colored hard capsule filled with 300 mg of each sample was taken orally for 6 months. The effects on the number of hairs, hair growth rate and hair diameter were evaluated by the following methods. That is, the number of hairs was measured per 1 cm 2 after taking an enlarged photograph of a predetermined part of the crown using a digital microscope (manufactured by Hilox Co., Ltd., KH-3000). As for the hair growth rate, first, a predetermined part of the parietal region was shaved 3 days before the final test day, and an enlarged photograph was taken with the digital microscope, and the length of the hair was analyzed. Next, the length of hair 72 hours after hair cutting was measured by the same method as described above. The length of the hair extended in 72 hours was converted per 24 hours, and this was defined as the hair growth rate (μm / 24 hr). The hair diameter was cut at a predetermined site, and then the enlarged hair was taken in the same manner as above to analyze the thickness of the hair. These measurements were carried out before ingesting the placebo and each sample and after ingesting for 6 months.

この結果を表2に示す。同表において、摂取試料が併用の場合は等質量混合物を示し、各数値はそれぞれの被験物質を6ヵ月間摂取した後の数値から、摂取する前の数値を差し引き、その変化を平均値±標準偏差で表わした(n=6、ANOVA解析)。表2のデータから、プラセボを摂取した被験者の毛髪数、毛髪成長速度及び毛髪径に有意な変化はみられなかったが、試料1(ノコギリヤシ果実抽出物)や試料2(カボチャ種子抽出物)を摂取した場合にはいずれの測定項目でも有意な変化が認められ、これらの混合物を摂取する場合にはシクロデキストリン包接物の形態(試料3)のとき前記変化が相乗的に発現することが明らかになった。また、試料3と血流促進作用の認められたものとを併用すると、前記変化はより一層大きくなり、とりわけ、ツバキ種子抽出物との併用(試料3+試料4、試料3+試料5、試料3+試料4+試料6)の場合、試料3と緑茶葉抽出物との併用(試料3+試料6、試料3+試料4+試料6)の場合には、前記変化が意外にも極めて顕著なものとなることが確認された。したがって、これらの組み合わせは発毛、育毛、養毛において有用である。なお、血流促進作用が既知のイチョウ葉抽出物やDHA含有油脂と試料3とを併用した場合の前記変化は、試料3単独の場合よりも高値であるが、ツバキ種子抽出物や緑茶葉抽出物との併用の場合に比べて小さかった。The results are shown in Table 2. In the same table, when the ingested sample is used in combination, it indicates an equal mass mixture. Each value is the average value ± standard after subtracting the value before ingestion from the value after ingesting each test substance for 6 months. Expressed by deviation (n = 6, ANOVA analysis). From the data in Table 2, there was no significant change in the number of hairs, hair growth rate and hair diameter of subjects who took placebo, but sample 1 (saw palm fruit extract) and sample 2 (pumpkin seed extract) When ingested, significant changes were observed in any of the measurement items, and when these mixtures were ingested, it was clear that the changes were synergistically expressed in the form of cyclodextrin inclusion (sample 3). Became. In addition, when the sample 3 and the blood flow promoting action are used in combination, the change is further increased, especially in combination with the camellia seed extract (sample 3 + sample 4, sample 3 + sample 5, sample 3 + sample). In the case of 4 + sample 6), it is confirmed that the above change is unexpectedly extremely remarkable in the case of combined use of sample 3 and green tea leaf extract (sample 3 + sample 6, sample 3 + sample 4 + sample 6). It was done. Therefore, these combinations are useful in hair growth, hair growth and hair restoration. In addition, although the said change when using Ginkgo biloba extract or DHA containing fats and oils with known blood flow promoting action in combination with Sample 3 is higher than that of Sample 3 alone, Camellia seed extract or Green tea leaf extraction It was small compared with the case of combined use.

Figure 2011105695
Figure 2011105695

試作例1(ソフトカプセル)
前記の試料1及び試料2(混合比:1/1)、試料3及び試料4(混合比:2/1)、試料3及び試料5(混合比:1/1)、試料3及び試料6(混合比:2/1)、試料3及び試料4及び試料6(混合比:1/1/1)のいずれか1種:200部に、ミツロウ:40部及び月見草油(英国エファモール社製):50部を加え、加熱混合して均質化後、カプセル充填機に供して、常法により1粒あたり内容量が250mgのゼラチン被覆ソフトカプセル製剤を試作した。このカプセル製剤は経口摂取可能な栄養補助食品、医薬品又は動物用飼料として利用することができる。
Prototype example 1 (soft capsule)
Sample 1 and sample 2 (mixing ratio: 1/1), sample 3 and sample 4 (mixing ratio: 2/1), sample 3 and sample 5 (mixing ratio: 1/1), sample 3 and sample 6 ( Mixing ratio: 2/1), any one of Sample 3, Sample 4 and Sample 6 (mixing ratio: 1/1/1): 200 parts, beeswax: 40 parts and evening primrose oil (manufactured by Efamol) After adding 50 parts, mixing by heating and homogenizing, the mixture was used in a capsule filling machine, and a gelatin-coated soft capsule preparation with an internal volume of 250 mg per grain was prepared by a conventional method. This capsule preparation can be used as an orally ingestible dietary supplement, pharmaceutical product or animal feed.

試作例2(ハードカプセル)
前記の試料3、試料3及び試料4(混合比:1/1)、試料3及び試料5(混合比:3/1)、試料3及び試料6(混合比:1/1)、試料3及び試料4及び試料6(混合比:2/1/1)のいずれか1種をカプセル充填機に供して、常法により1粒あたり内容量が200mgのゼラチン被覆ハードカプセル製剤を試作した。このカプセル製剤は経口摂取可能な栄養補助食品、医薬品又は動物用飼料として利用することができる。
Prototype 2 (hard capsule)
Sample 3, Sample 3 and Sample 4 (mixing ratio: 1/1), Sample 3 and Sample 5 (mixing ratio: 3/1), Sample 3 and Sample 6 (mixing ratio: 1/1), Sample 3 and Any one of Sample 4 and Sample 6 (mixing ratio: 2/1/1) was subjected to a capsule filling machine, and a gelatin-coated hard capsule preparation having an internal volume of 200 mg per grain was prepared by a conventional method. This capsule preparation can be used as an orally ingestible dietary supplement, pharmaceutical product or animal feed.

試作例3(錠剤)
前記の試料3、試料3及び試料4(混合比:3/1)、試料3及び試料5(混合比:2/1)、試料3及び試料6(混合比:3/1)、試料3及び試料4及び試料6(混合比:3/2/1)のいずれか1種:30部、カルボキシメチルセルロース:70部、コーンスターチ:40部、マンニトール:20部、リン酸三カルシウム:30部、パントテン酸カルシウム:10部及びブドウ茎抽出物(BioseraeLab社製、Resveravine):10部を混合機に仕込み、10分間攪拌混合した。この混合物を直打式打錠機に供して直径7mm、高さ4mm、150mg/個の素錠を作成し、次いでコーティング機でシェラック被膜を形成させて錠剤を試作した。この錠剤は経口摂取可能な栄養補助食品、医薬品又はペット用飼料として利用することができる。
Prototype 3 (tablet)
Sample 3, Sample 3 and Sample 4 (mixing ratio: 3/1), Sample 3 and Sample 5 (mixing ratio: 2/1), Sample 3 and Sample 6 (mixing ratio: 3/1), Sample 3 and Any one of Sample 4 and Sample 6 (mixing ratio: 3/2/1): 30 parts, carboxymethylcellulose: 70 parts, corn starch: 40 parts, mannitol: 20 parts, tricalcium phosphate: 30 parts, pantothenic acid 10 parts of calcium and 10 parts of grape stem extract (manufactured by BioseraeLab, Resveravine): 10 parts were charged into a mixer and mixed with stirring for 10 minutes. This mixture was subjected to a direct compression tableting machine to prepare uncoated tablets having a diameter of 7 mm, a height of 4 mm, and 150 mg / piece, and then a shellac film was formed by the coating machine to produce a tablet. This tablet can be used as an orally ingestible dietary supplement, pharmaceutical or pet feed.

試作例4(飲料)
市販の栄養ドリンク100mLに試料3及び試料4(混合比:2/1)、試料3及び試料5(混合比:3/1)、試料3及び試料6(混合比:1/1)のいずれか1種:250mgを加えて十分に混合し飲料を試作した。これは冷蔵庫で6ヵ月間保存しても外観及び風味に異状及び違和感は認められなかった。本品は発毛、育毛、養毛等のための飲料やドリンク剤として利用することができる。
Prototype Example 4 (Beverage)
Sample 3 and sample 4 (mixing ratio: 2/1), sample 3 and sample 5 (mixing ratio: 3/1), sample 3 and sample 6 (mixing ratio: 1/1) in 100 mL of commercially available nutrition drink Type 1: 250 mg was added and mixed well to prepare a beverage. Even when this was stored in a refrigerator for 6 months, no abnormalities or discomfort was observed in the appearance and flavor. This product can be used as a beverage or drink for hair growth, hair growth, hair growth and the like.

本発明の、ノコギリヤシ果実抽出物及びカボチャ種子抽出物、該両抽出物とツバキ種子抽出物及び/又は緑茶葉抽出物との併用物を有効成分として含む発毛促進剤は、これを経口で摂取又は投与することにより発毛促進、育毛及び/又は養毛の作用を有するため、飲食品、医薬品、医薬部外品、飼料等の分野において有効利用できる。The hair growth promoter of the present invention comprising a saw palm fruit extract and a pumpkin seed extract, a combination of the two extracts and a camellia seed extract and / or a green tea leaf extract as an active ingredient, is taken orally. Or, since it has the action of promoting hair growth, hair growth and / or hair nourishment by administration, it can be effectively used in the fields of foods and drinks, pharmaceuticals, quasi drugs, feeds and the like.

Claims (8)

ノコギリヤシ果実抽出物及びカボチャ種子抽出物を有効成分として含有してなる経口発毛促進剤。An oral hair growth promoter comprising a saw palm fruit extract and a pumpkin seed extract as active ingredients. ノコギリヤシ果実抽出物及びカボチャ種子抽出物がシクロデキストリンで包接されたものである請求項1に記載の経口発毛促進剤。The oral hair growth-promoting agent according to claim 1, wherein the saw palm fruit extract and the pumpkin seed extract are clathrated with cyclodextrin. 血流改善作用物質を併用するものである請求項1又は2に記載の経口発毛促進剤。The oral hair growth promoter according to claim 1 or 2, which is used in combination with a blood flow improving agent. 血流改善作用物質がツバキ種子抽出物及び/又は緑茶葉抽出物である請求項3に記載の経口発毛促進剤。4. The oral hair growth promoter according to claim 3, wherein the blood flow improving agent is a camellia seed extract and / or a green tea leaf extract. ツバキ種子抽出物がツバキ種子の脱脂物を水及び/又は低級アルコールで抽出処理して得られる水溶性成分を含むものである請求項4に記載の経口発毛促進剤。5. The oral hair growth promoter according to claim 4, wherein the camellia seed extract contains a water-soluble component obtained by subjecting a camellia seed defatted product to extraction treatment with water and / or a lower alcohol. ツバキ種子抽出物がサポニン類を含有するものである請求項4又は請求項5に記載の経口発毛促進剤。The oral hair growth promoter according to claim 4 or 5, wherein the camellia seed extract contains saponins. 飲食品として使用する請求項1〜6のいずれか1項に記載の経口発毛促進剤。The oral hair growth promoter according to any one of claims 1 to 6, which is used as a food or drink. 形態が粉末、顆粒、錠剤、カプセル又は液体である請求項7に記載の経口発毛促進剤。The oral hair growth promoter according to claim 7, wherein the form is powder, granule, tablet, capsule or liquid.
JP2009276977A 2009-11-13 2009-11-13 Oral hair growth promoter Active JP5617110B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2009276977A JP5617110B2 (en) 2009-11-13 2009-11-13 Oral hair growth promoter

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2009276977A JP5617110B2 (en) 2009-11-13 2009-11-13 Oral hair growth promoter

Publications (2)

Publication Number Publication Date
JP2011105695A true JP2011105695A (en) 2011-06-02
JP5617110B2 JP5617110B2 (en) 2014-11-05

Family

ID=44229607

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2009276977A Active JP5617110B2 (en) 2009-11-13 2009-11-13 Oral hair growth promoter

Country Status (1)

Country Link
JP (1) JP5617110B2 (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013245213A (en) * 2012-05-29 2013-12-09 Jx Nippon Oil & Energy Corp Clathrate of eriobotrya japonica leaf culture extract and cyclodextrin
KR101452320B1 (en) * 2014-03-11 2014-10-22 주식회사 벤스랩 FERMENTED CAMELLIA JAPONICA SEED OIL INHIBITING 5-α REDUCTASE FOR IMPROVEMENT OF BENIGN PROSTATIC HYPERPLASIA AND ALOPECIA
JP2016030748A (en) * 2014-07-30 2016-03-07 株式会社イムダイン Hair restoration and scalp improving agent by oral administration
US9505841B2 (en) 2013-09-17 2016-11-29 Samsung Electronics Co., Ltd. Use of an anti-Ang2 antibody
US9828422B2 (en) 2013-07-29 2017-11-28 Samsung Electronics Co., Ltd. Anti-Ang2 antibody
JP2019213518A (en) * 2018-06-11 2019-12-19 株式会社神鋼環境ソリューション Testosterone secretion promoter

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20230052470A (en) 2021-10-13 2023-04-20 (주)아모레퍼시픽 Composition for promoting hair growth

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001078716A (en) * 1999-09-09 2001-03-27 Jiinasu:Kk Treatment of vegetable and animal crude drug and healthy food material and crude drug and healthy food
US6261607B1 (en) * 1999-10-19 2001-07-17 Thomas Newmark Composition for promoting prostate health containing selenium and herbal extracts
JP2002322050A (en) * 2001-04-25 2002-11-08 Kenji Uehara Hair growth agent
JP2004307443A (en) * 2003-04-10 2004-11-04 Shiseido Co Ltd Caspase-9 activity inhibitor-containing composition
US20060009430A1 (en) * 2004-07-01 2006-01-12 Kelly Gregory J Composition for the prevention and treatment of the detrimental effects of dihydrotestosterone
JP2008100977A (en) * 2006-10-20 2008-05-01 Shin Endo Pilatory and hair growing agent
JP2008163002A (en) * 2006-12-08 2008-07-17 Bhn Kk Obesity-preventing and improving agent

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001078716A (en) * 1999-09-09 2001-03-27 Jiinasu:Kk Treatment of vegetable and animal crude drug and healthy food material and crude drug and healthy food
US6261607B1 (en) * 1999-10-19 2001-07-17 Thomas Newmark Composition for promoting prostate health containing selenium and herbal extracts
JP2002322050A (en) * 2001-04-25 2002-11-08 Kenji Uehara Hair growth agent
JP2004307443A (en) * 2003-04-10 2004-11-04 Shiseido Co Ltd Caspase-9 activity inhibitor-containing composition
US20060009430A1 (en) * 2004-07-01 2006-01-12 Kelly Gregory J Composition for the prevention and treatment of the detrimental effects of dihydrotestosterone
JP2008100977A (en) * 2006-10-20 2008-05-01 Shin Endo Pilatory and hair growing agent
JP2008163002A (en) * 2006-12-08 2008-07-17 Bhn Kk Obesity-preventing and improving agent

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013245213A (en) * 2012-05-29 2013-12-09 Jx Nippon Oil & Energy Corp Clathrate of eriobotrya japonica leaf culture extract and cyclodextrin
US9828422B2 (en) 2013-07-29 2017-11-28 Samsung Electronics Co., Ltd. Anti-Ang2 antibody
US9902767B2 (en) 2013-07-29 2018-02-27 Samsung Electronics Co., Ltd. Method of blocking vascular leakage using an anti-ANG2 antibody
US11174309B2 (en) 2013-07-29 2021-11-16 Samsung Electronics Co., Ltd. Anti-ANG2 antibody
US9505841B2 (en) 2013-09-17 2016-11-29 Samsung Electronics Co., Ltd. Use of an anti-Ang2 antibody
KR101452320B1 (en) * 2014-03-11 2014-10-22 주식회사 벤스랩 FERMENTED CAMELLIA JAPONICA SEED OIL INHIBITING 5-α REDUCTASE FOR IMPROVEMENT OF BENIGN PROSTATIC HYPERPLASIA AND ALOPECIA
WO2015137652A1 (en) * 2014-03-11 2015-09-17 주식회사 벤스랩 5-alpha reductase inhibiting fermented camellia japonica seed oil for alleviating benign prostatic hypertrophy and baldness
JP2016030748A (en) * 2014-07-30 2016-03-07 株式会社イムダイン Hair restoration and scalp improving agent by oral administration
JP2019213518A (en) * 2018-06-11 2019-12-19 株式会社神鋼環境ソリューション Testosterone secretion promoter

Also Published As

Publication number Publication date
JP5617110B2 (en) 2014-11-05

Similar Documents

Publication Publication Date Title
JP5617110B2 (en) Oral hair growth promoter
JP6640392B2 (en) Obesity control composition
KR102262306B1 (en) Composition for relieving premenstrual syndrome and menstrual pain
JP5685752B2 (en) Blood flow promoting agent
KR20110004603A (en) Extracts from sophora japonica l. for treating or preventing menopausal complaints, skin-aging, or skin wrinkle
KR102153414B1 (en) Composition for improving hair loss and promoting hair growth containing a fermented soybean
WO2007133054A1 (en) A novel process for preparing black ginseng and the composition comprising the same
JP5066725B2 (en) Fat absorption inhibitor, fat accumulation inhibitor or fat burning accelerator
KR101726757B1 (en) Composition for prevention and treatment of climacteric disorder comprising extracts of Dendropanax morbifera as an active ingredient
JP5597828B2 (en) Hair restorer
JP2003055244A (en) Agent promoting hyaluronic acid production, cosmetics, food and beverage including the hyaluronic acid production-promoting agent
KR101749967B1 (en) A pharmaceutical composition comprising extract from germinated gemmule of bean for preventing or treating obesity
JP2013184974A (en) Maillard reaction inhibitor and use thereof
KR101821925B1 (en) A composition comprising the complex extract of Poncirus trifoliata and Cinnamommum cassia for treating or preventing allergy desmatitis
JP2008163003A (en) Fat absorption inhibitor
JP2008163004A (en) Fat accumulation inhibitor
JP7296611B2 (en) Nitric oxide production accelerator
JP2015110536A (en) Fatigue improvement composition
KR101525877B1 (en) A composition for preventing wrinkle of skin and anti aging of skin
KR101738206B1 (en) A composition comprising the complex extract of Poncirus trifoliata and Cinnamommum cassia for treating or preventing allergy desmatitis
KR20180098883A (en) Composition for anti-obesity or reducing body-fat having extract of peanut sprouts as active component
JP2008163005A (en) Fat combustion-promoting agent
KR20170072055A (en) An anti­oxidant composition comprising the pachyrhizus erosus root bark extract
KR20170025363A (en) Composition for improving skin
JP7312954B2 (en) Composition

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20121102

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20140218

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20140421

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20140812

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20140827

R150 Certificate of patent or registration of utility model

Ref document number: 5617110

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250