JP2004075640A - Agent for inhibiting differentiation of lipocyte - Google Patents
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Abstract
Description
【0001】
【発明の属する技術分野】
本発明は前駆脂肪細胞の分化抑制剤に関し、更に詳しくは成熟脂肪細胞数を抑制し全身及び/又は局所の過剰な脂肪の蓄積を防ぐことにより肥満を解消し防止する食品、医薬または化粧料に関する。
【0002】
【従来の技術】
従来、からだの脂肪組織及び種々の臓器における異常な脂肪沈着による肥満、あるいは高脂血症は、高血圧、動脈硬化、糖尿病などの各種生活習慣病の発症に密接に関与していると考えられている。
また肥満は体の均整を失わせ、外観を著しく損なうため、美容の分野においても大きな問題となっている。皮下脂肪組織では局所的な脂肪細胞の肥大化により皮下結合組織の膨潤がおこり、オレンジ果皮にたとえられる皮膚表面の凸凹、すなわち蜂巣炎を引き起こす。
【0003】
肥満は、体質的因子、食餌性因子、精神的因子、中枢性因子、代謝性因子、運動不足などが要因となり、結果的に摂取カロリーが消費カロリーを上回り、脂肪が蓄積して起こると言われている。肥満では、生体内における個々の脂肪細胞の蓄積している脂肪、すなわちトリグリセリド量が増加し細胞が肥大化している。また近年、成人期以降でも脂肪細胞数が増加することが明らかとなり、前駆脂肪細胞から成熟脂肪細胞への分化を抑制し、成熟脂肪細胞数を減少させることや、成熟脂肪細胞の脂肪蓄積を抑制することにより肥満の進行を抑え、肥満を改善させることが期待される。
【0004】
脂肪細胞数の増加を抑制し抗肥満効果を示す食品または医薬または化粧料としてはあまり多くはなく、例えば前駆脂肪細胞分化抑制ペプチドを有効成分とするもの(特許文献1)や、活性化乳清を有効成分とするもの(特許文献2)がある。またω−3系高度不飽和脂肪酸を有効成分として皮膚外用剤に適用させる(特許文献3)試みがある。しかしながら、未だ十分な効果がなく、新規な前駆脂肪細胞分化抑制剤が望まれていた。
【0005】
【特許文献1】
特開平6−293796号公報
【特許文献2】
特開2000−37738号公報
【特許文献3】
特開平11−130656号公報
【0006】
【発明が解決しようとする課題】
本発明の課題は、副作用の恐れがない、効果的で安全性の高い前駆脂肪細胞分化抑制剤、抗肥満剤、蜂巣炎改善剤、およびこれらを含有する食品、医薬および化粧料を提供することにある。
【0007】
【課題を解決するための手段】
本発明者は、ある特定のキノコ及び植物に強い前駆脂肪細胞分化抑制活性を見出し、本発明を完成させた。
すなわち、本発明は、
1.カワラタケ、カノコソウ、ウワマサマナ、パスチャカ、パイコ、アグラヤホ、ガジュツ、カミツレ、クマザサ、グアバ葉、カッファライム、ジュニパーベリー、ナツメグ、バジル、メース、レモングラス、ローズマリー、柿の葉、ギムネマシルベスタ、青銭柳、レモンバーベナから成るキノコ、植物又は植物の部位群より選ばれる少なくとも1種を含有する前駆脂肪細胞の分化抑制剤、
2.1記載のキノコ、植物又は植物の部位群より選ばれる少なくとも1種を含有する脂肪細胞の脂肪蓄積阻害剤、
3.1記載のキノコ、植物又は植物の部位群(クマザサ、グアバ葉、ギムネマシルベスタを除く)より選ばれる少なくとも1種を含有する抗肥満剤、
4.クマザサ、グアバ葉又はギムネマシルベスタを前駆脂肪細胞の分化抑制剤として含む、抗肥満用組成物、
5.1記載のキノコ、植物又は植物の部位群より選ばれる少なくとも1種を含有する蜂巣炎改善剤、
6.1〜5のいずれかの剤又は組成物を含有する食品、
7.1〜5のいずれかの剤又は組成物を含有する医薬、及び
8.1〜5のいずれかの剤又は組成物を含有する化粧料、
に関する。
【0008】
【発明の実施の形態】
本発明で使用されるキノコはカワラタケ(Coriolus versicolor(L.:Fr.)Quel)が使用可能であり、また植物はカノコソウ(Valeriana fauriei)、ウワマサマナ(Jacaranda copaia)、パスチャカ(Geranium dielsianum)、パイコ(Chenopodium ambrosioides)、アグラヤホ(Berberis vulgaris)、ガジュツ(Curcuma zeodaris)、カミツレ(Matricaria chamomilla)、クマザサ(Sasa veitchii)、グアバ葉(Psidium guajava L.)、カッファライム(Citrus hystrix)、ジュニパーベリー(Juniperus communis)、ナツメグ(Myristica fragrans)、バジル(Ocimum basilicum)、メース(Myristica fragrans)、レモングラス(Cymbopogon citratus)、ローズマリー(Rosmarinus officinalis)、柿の葉(Diospyros kaki)、ギムネマシルベスタ(Gymnema sylvestris)、青銭柳(Cyclocarya paliurus)、レモンバーベナ(Lippia citriodora)が使用可能であり、通常食用として供されているものでも、適当な溶媒を用いて抽出した抽出物でも構わない。
【0009】
カワラタケ(Coriolus versicolor(L.:Fr.)Quel)は担子菌類、サルノコシカケ科のキノコのことであり、亜熱帯から亜寒帯にかけて広く分布する。この菌の培養菌糸から分離した複合多糖類は抗腫瘍作用のあることがわかり、臨床的に応用されている。
カノコソウ(Valeriana fauriei)はオミナエシ科の双子葉植物の多年草のことであり、北海道から九州、サハリン、朝鮮、中国に分布する。根には約8%の精油が含まれ、特有の臭気があり、漢方で精神不安定やヒステリーの鎮静にして用いられる。
ウワマサマナ(Jacaranda copaia)はノウゼンカズラ科の双子葉植物の高木のことであり、中米、南米北部に分布する。薬効、薬理に関する詳細は不明であるが、葉、樹皮にはアルカロイド、カテキン、ステロイド、フェノール、サポニン、タンニンを含む。
【0010】
パスチャカ(Geranium dielsianum)はフウロソウ科の双子葉植物のことで、中南米に分布する。薬効、薬理に関する詳細は不明であるが、民間的に血糖降下作用、膵臓機能強化作用が知られ、糖尿病治療補助に用いられる。
パイコ(Chenopodium ambrosioides)はアカザ科の双子葉植物の一年草のことで、ケアリタソウとも呼ばれているものである。世界の温暖な地域に広く分布しており、日本でも見られる。強力な駆虫作用が知られており、消化促進、胃炎、抗鼓腸作用に対しても利用される。
アグラヤホ(Berberis vulgaris)はメギ科の双子葉植物の落葉の低木のことであり、セイヨウメギとも呼ばれているものである。ヨーロッパから中部アジアにかけて分布し、果実は食用になり、栽培もされた。ヨーロッパでは慢性消化不良、便秘、健胃、腎臓結石などに民間薬として利用される。
【0011】
ガジュツ(Curcuma zeodaris)はショウガ科の単子葉植物の多年草のことである。インドから東南アジアを中心として熱帯や亜熱帯で広く栽培されている。漢方では健胃、去痰薬として用いられる。
カミツレ(Matricaria chamomilla)はキク科の双子葉植物のことであり、ヨーロッパから西アジアに分布し、薬用に栽培もされている。ヨーロッパでは茶として、また民間薬として抗炎症、駆風、健胃、発汗、精神不安定等に用いられる。
クマザサ(Sasa veitchii)はイネ科の単子葉植物のことであり、日本の特産で、自生する他、観賞用としてもよく植えられている。薬効、薬理に関する詳細は不明であるが、葉は民間薬として健胃、糖尿病、高血圧に用いられる。
【0012】
グアバ葉(Psidium guajava L.)はフトモモ科の双子葉植物の常緑低木であり、バンジロウとも呼ばれるものである。熱帯アメリカが原産地熱帯から亜熱帯域に分布する。果実は生食する他、主としてジュースとして利用される。葉を茶として利用する習慣があり、近年高血圧に有効であることが明らかにされている。
カッファライム(Citrus hystrix)はミカン科の双子葉植物の低木であり、スワンギ、コブミカンとも呼ばれるものである。熱帯アジアに分布している。果実は黄熟し果汁が多く、酸味、苦みが強い。薬味として用いられる。
ジュニパーベリー(Juniperus communis)はヒノキ科の裸子植物の高木であり、セイヨウネズ、トショウシとも呼ばれるものである。北半球に広く分布し、その球果を入れた蒸留酒がジンである。消化促進、水分***促進作用が知られており、尿道の疾病に用いられる。
【0013】
ナツメグ、メース(Myristica fragrans)はニクズク科の双子葉植物の常緑高木の種子である。種子を包む仮種皮を除いたものがナツメグ、網目状の朱肉色の仮種皮がメースである。海洋性気候に適し、熱帯の島でよく育ち、現在ではインドネシア、東アフリカ、西インド諸島などが産地である。ミリスチシン、ピネン、オイゲノール、サフロールなどの精油成分を含み、香辛料として汎用されている。漢方では消化不良、腹痛、下痢などに用いられる。
バジル(Ocimum basilicum)はシソ科の双子葉植物であり、メボウキとも呼ばれるものである。熱帯アジアの原産と考えられているが、現在は世界各地で栽培されている。エストラゴール、オイゲノール、リネオール、リナロール、チモール、タンニン、バジルカンファーなどの精油成分を含み、香辛料、香草として汎用されている。薬用としても鎮咳、解熱、駆風、動悸、便秘、淋病に用いられる。
【0014】
レモングラス(Cymbopogon citratus)はイネ科の単子葉植物であり、レモンソウとも呼ばれるものである。インド亜大陸原産とされる多年草で、全草にレモンのような芳香を発する精油を含み、熱帯や亜熱帯地域で栽培される。シトラールなどの精油成分を香料用とする他、香辛料として、また薬用として風邪の頭痛、胃痛、関節疼痛、月経不順、食欲不振に用いられる。
ローズマリー(Rosmarinus officinalis)はシソ科の双子葉植物の常緑の小低木であり、マンネンロウとも呼ばれるものである。地中海沿岸地方原産でピネン、シネオール、竜脳、樟脳などの精油成分を含みローズマリー油と呼ばれる香油が香料として利用される。香辛料、香草として料理に用いられる。また精油成分、全草とも薬用として消化促進、駆風、利尿、抗うつ、強心、婦人病、鎮静、抗炎症など広く用いられる。
【0015】
柿の葉(Diospyros kaki)はカキノキ科の双子葉植物の落葉高木の葉である。東アジア温帯に分布、現在は耐寒性のあるカキノキ科の果樹として熱帯高地や欧米の温暖な地域でも栽培されている。果実には糖類、ペクチン、カロチノイド、ビタミンCが多く含まれ、食用にする。渋味はタンニンによるもので、様々な方法でタンニンを不溶化し渋抜きされる。葉はケンフェロール配糖体、ケルセチン配糖体等、ビタミンCを含み民間薬として高血圧症に用いられる。
ギムネマシルベスタ(Gymnema sylvestris)とは、ガガイモ科の双子葉植物のことであり、中国南部、台湾、ベトナム、インド、その他熱帯各地に分布し、低木林などに生える常緑つる性植物である。葉にはギムネマ酸と呼ばれるトリテルペン配糖体が含まれ、これが糖吸収抑制、血糖上昇抑制、抗う蝕性作用があることが知られている。ギムネマ葉のアルコールエキスは成長ホルモンもしくは副腎皮質ホルモンによる血糖上昇を抑制する。中国では乳腺炎、外傷、腫れ物などに用いられている。
【0016】
青銭柳(Cyclocarya paliurus)はクルミ科の双子葉植物の高木であり、中国の広東省、広西チワン族自治区、貴州省、湖南省、湖北省、四川省、福建省、江西省、浙江省、安徽省に生育する。薬効、薬理に関する詳細は不明であるが、近年民間薬として血糖値上昇抑制に用いられる。
レモンバーベナ(Lippia citriodora)はクマツヅラ科の双子葉植物であり、熱帯から亜熱帯に分布する常緑の低木であり、ボウシュウボクとも呼ばれるものである。南米のペルー、チリ、ブラジルの一部に分布し、茶の代用として、また食品に香気をつけるために栽培、利用される。リモネン、ジペンテン、シネオール、シトラール、メチルヘプテノン等の精油成分を含み、健胃作用があると言われ、消化薬として用いられる。また鎮痙、強壮作用があると言われている。
【0017】
植物としては、葉、茎、芽、花、木質部、木皮部(樹皮)などの地上部および根、塊茎などの地下部、種子、果実、樹脂など全ての部位が使用可能である。
キノコ、植物又はその部位は、それ自身を乾燥させた乾燥物、その粉砕物、それら自身を圧搾抽出することにより得られる搾汁、水あるいはアルコール、エーテル、アセトンなどの有機溶媒による粗抽出物、および粗抽出物を分配、カラムクロマトなどの各種クロマトグラフィーなどで段階的に精製して得られた抽出物画分など、全てを含む。これらは単独で用いても良く、また2種以上混合して用いても良い。
例えば、カノコソウ(Valeriana fauriei)の植物体乾燥物1Kgに99.5%エタノール抽出液3Lを加え、室温で一晩浸漬することにより得た抽出液を、そのまま使用しても良いし、各種クロマトグラフィーを組み合わせて、精製したものを使用しても良い。
【0018】
これらの本発明による特定のキノコ、植物、植物部位の乾燥物または抽出物に、前駆脂肪細胞の分化抑制活性を有することは、従来から全く知られておらず、本発明により得られた新知見である。
本発明のキノコ、植物、植物部位の乾燥物または抽出物は、卓越した前駆脂肪細胞の分化抑制活性を有しており、脂肪蓄積阻害剤、抗肥満剤、蜂巣炎改善剤、及びこれらを含有する食品、医薬及び化粧料として使用可能である。
キノコ、植物、植物部位の乾燥物または抽出物を、前駆脂肪細胞の分化抑制剤、脂肪蓄積阻害剤、抗肥満剤、蜂巣炎改善剤、及びこれらを含有する食品、医薬及び化粧料として製造することができる。
【0019】
医薬としての適用方法は、経口投与又は非経口投与のいずれも採用することができる。投与に際しては、有効成分を経口投与、直腸内投与、注射などの投与方法に適した固体又は液体の医薬用無毒性担体と混合して、慣用の医薬製剤の形態で投与することができる。このような製剤としては、例えば、錠剤、顆粒剤、散剤、カプセル剤などの固形剤、溶液剤、懸濁剤、乳剤などの液剤、凍結乾燥製剤などが挙げられ、これらの製剤は製剤上の常套手段により調製することができる。上記の医薬用無毒性担体としては、例えば、グルコース、乳糖、ショ糖、澱粉、マンニトール、デキストリン、脂肪酸グリセリド、ポリエチレングルコール、ヒドロキシエチルデンプン、エチレングリコール、ポリオキシエチレンソルビタン脂肪酸エステル、アミノ酸、ゼラチン、アルブミン、水、生理食塩水などが挙げられる。また、必要に応じて、安定化剤、湿潤剤、乳化剤、結合剤、等張化剤などの慣用の添加剤を適宜添加することもできる。
【0020】
食品としては、そのまま、又は種々の栄養成分を加えて、若しくは飲食品中に含有せしめて、蜂巣炎あるいは肥満の治療及び予防に有用な保健用食品又は食品素材として食される。例えば、上述した適当な助剤を添加した後、慣用の手段を用いて、食用に適した形態、例えば、顆粒状、粒状、錠剤、カプセル、ペーストなどに成形して食用に供してもよく、また種々の食品、例えば、ハム、ソーセージなどの食肉加工食品、かまぼこ、ちくわなどの水産加工食品、パン、菓子、バター、粉乳、発酵乳製品に添加して使用したり、水、果汁、牛乳、清涼飲料などの飲料に添加して使用してもよい。
【0021】
有効投与量は、患者の年齢、体重、症状、患者の程度、投与経路、投与スケジュール、製剤形態、素材の阻害活性の強さなどにより、適宜選択・決定されるが、例えば、経口投与の場合、一般に1日当たり0.001〜1000mg/kg体重程度、ウアマサマナ(Jacaranda copaia)の熱水抽出物の場合、1日当たり1〜300mg/kg体重程度とされ、1日に数回に分けて投与してもよい。
【0022】
また、化粧料または化粧料素材として使用する場合、例えば、カワラタケ(Coriolus versicolor(L.:Fr.)Quel)の乾燥物あるいは抽出物を小麦胚芽油あるいはオリーブ油に添加して前駆脂肪細胞分化抑制剤含有組成物とし、これを化粧料素材として使用することができる。添加量は、特に限定されるものではないが、一例としてあげると、小麦胚芽油あるいはオリーブ油の重量に対して0.1質量%以上60質量%以下、好ましくは、0.5質量%以上50質量%以下が適当である。
また、直接、化粧料成分として使用し、前駆脂肪細胞分化作用を有する化粧料を製造することができる。
【0023】
化粧料としては特に限定されるものではないが、機能面からは、例えばフェイス又はボディ用乳液、化粧液、クリーム、ローション、エッセンス、パック、シートなどが好ましい。
このような化粧料は、常法に従って製造することができる。化粧料における添加量は、特に限定されるものではないが、一例としてあげると、化粧料全重量の0.01質量%以上20質量%以下程度が適当である。
本発明の植物は、天然物であるためその毒性は低く、例えばローズマリー(Rosmarinus officinalis)の熱水抽出物を毎日1000mg/kg、100日間という長期間に亘ってラットに経口投与しても、死亡例は認められず、体重変化も観察されなかった。
【0024】
【実施例】
以下に実施例を挙げて、具体的に説明するが、これに限定されるものではない。
【0025】
[薬理試験]
試料の調製 1:カワラタケ
カワラタケ(Coriolus versicolor)約1200個(湿重量700g)をミキサーで粉砕後、80%エタノール−水5Lに3日間浸漬した。減圧ろ過によるろ液をエバポレータで濃縮して粗抽出物16.6gを褐色油状物として得た。この粗抽出物を水400mLと酢酸エチル400mLで分配した。得られた水層を更に2回酢酸エチル400mLで分配し、酢酸エチル層を全て集め、エバポレータで濃縮して酢酸エチル可溶物1.21gを褐色油状物として得た。これを脂肪蓄積率測定用試料とした。
【0026】
試料の調製 2:植物
カノコソウ(Valeriana fauriei)、ウワマサマナ(Jacaranda copaia)、パスチャカ(Geranium dielsianum)、パイコ(Chenopodium ambrosioides)、アグラヤホ(Berberis vulgaris)、ガジュツ(Curcuma zeodaris)、カミツレ(Matricaria chamomilla)、クマザサ(Sasa veitchii)、グアバ葉(Psidium guajava L.)、カッファライム(Citrus hystrix)、ジュニパーベリー(Juniperuscommunis)、ナツメグ(Myristica fragrans)、バジル(Ocimum basilicum)、メース(Myristica fragrans)、レモングラス(Cymbopogon citratus)、ローズマリー(Rosmarinus officinalis)、柿の葉(Diospyros kaki)、ギムネマシルベスタ(Gymnema sylvestris)、青銭柳(Cyclocarya paliurus)、レモンバーベナ(Lippia citriodora)の植物、各100gに80%エタノール−水300mlを加え、3日間浸漬した後、ろ液を凍結乾燥することにより、各エタノール抽出乾燥物520、780、10560、820、4040、1260、1160、520、1200、1620、7500、5000、1240、17600、2160、6440、2920、4840、900、1800mgを得た。これを脂肪蓄積率測定用試料とした。
【0027】
[前駆脂肪細胞脂肪蓄積率の測定]
24穴マイクロプレート2枚に、マウス由来前駆脂肪細胞(3T3−L1)を培養用培地(10%牛胎児血清含有DMEM(グルコース濃度4500mg/mL))1mL中、コンフルエントに達するまで5%CO2存在下、37℃で7日間培養した。2枚とも同様に、培地を吸引除去し分化誘導培地(10%牛胎児血清含有DMEM(グルコース濃度4500mg/mL)に1μM デキサメタゾン、10μg/mL インシュリン 及び0.5mM 3−イソブチル−1−メチルキサンチンを溶解した培地)1.5mLに交換し、続いて試料のメタノール溶液を7.5μL添加した。この時対照として分化誘導培地に交換しないウェルと試料溶液の代わりにメタノールのみを添加したウェルも準備した。5%CO2存在下、37℃で6日間培養し、1枚は脂肪量測定用、他の1枚は生存率測定用とした。
【0028】
脂肪量測定用の1枚について、各ウェルに2%トライトン−X100を100μL添加し、30分間静置後シーリングテープ(朝日テクノグラス製)を貼って超音波洗浄器上で1分間超音波をかけた。各ウェル内容液を20μLづつ96穴マイクロプレートに採取し、トリグリセリドG−テストワコー(和光純薬工業製)の発色試薬100μLを添加して37℃で30分間培養後、プレートリーダーで吸光度(550nm)を測定した。試料添加群の吸光度の試料無添加群の吸光度に対する割合を百分率で求め、脂肪蓄積率とした。得られた各試料の脂肪蓄積率を表1に示す。脂肪蓄積率の低いものほど、脂肪細胞の分化を抑制していると見ることができる。
【0029】
[安全性試験]
生存率測定用の1枚について、各ウェルにセルカウンティングキット(同仁化学研究所製)20μLを添加し、37℃で4時間培養後、プレートリーダーで吸光度(450nm)を測定した。試料添加群の吸光度の試料無添加群の吸光度に対する割合を百分率で求め、細胞生存率とした。得られた各試料の細胞生存率を表1に示す。いずれのキノコ、植物又は植物の部位も安全性に問題ないことがわかる。
【0030】
【表1】
【0031】
処方例1
[錠剤の製造]
薬理試験の試料調製で得られたレモンバーベナ(Lippia citriodora)のエタノール抽出物を用いて、常法に従って、下記の組成の錠剤を製造した。
【0032】
処方例2
[ジュースの製造]
薬理試験の試料調製で得られたカミツレ(Matricaria chamomilla)のエタノール抽出物を用いて、常法に従って、下記の組成のジュースを製造した。
【0033】
処方例3
[フェイスクリームの製造]
薬理試験の[試料調製]で得られたジュニパーベリー(Juniperus communis)のエタノール抽出物を用いて、常法に従って、下記の組成のフェイスクリームを製造した。
【0034】
【発明の効果】
本発明のキノコ及び植物、植物部位は、前駆脂肪細胞の分化を強力に抑制することから、脂肪の蓄積や肥満の抑制、改善に寄与し得ると共に、局所的な脂肪細胞の肥大に起因する蜂巣炎の予防、治療に有効である。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a preadipocyte differentiation inhibitor, and more particularly to a food, medicine or cosmetic which suppresses and prevents obesity by suppressing the number of mature adipocytes and preventing systemic and / or local accumulation of excessive fat. .
[0002]
[Prior art]
Conventionally, obesity due to abnormal fat deposition in body adipose tissue and various organs, or hyperlipidemia is considered to be closely involved in the development of various lifestyle-related diseases such as hypertension, arteriosclerosis, and diabetes. I have.
Obesity is also a major problem in the field of beauty because it causes the body to lose its shape and its appearance is significantly impaired. In the subcutaneous adipose tissue, local enlargement of fat cells causes swelling of the subcutaneous connective tissue, which causes unevenness of the skin surface, which is compared to orange peel, that is, cellulitis.
[0003]
Obesity is said to be caused by constitutional factors, dietary factors, mental factors, central factors, metabolic factors, lack of exercise, etc., resulting in calories ingested exceeding calories consumed and fat accumulation. ing. In obesity, the amount of fat, that is, triglyceride, accumulated in individual fat cells in a living body increases, and the cells are enlarged. In recent years, it has been clarified that the number of adipocytes increases even after adulthood, suppressing the differentiation of preadipocytes into mature adipocytes, reducing the number of mature adipocytes, and suppressing fat accumulation in mature adipocytes. By doing so, it is expected that the progress of obesity will be suppressed and obesity will be improved.
[0004]
There are not many foods, medicaments or cosmetics which suppress the increase in the number of fat cells and exhibit an anti-obesity effect. For example, those containing a preadipocyte differentiation-inhibiting peptide as an active ingredient (Patent Document 1) and activated whey (Patent Document 2). There is also an attempt to apply an ω-3 type highly unsaturated fatty acid as an active ingredient to an external preparation for skin (Patent Document 3). However, there is still no sufficient effect, and a novel inhibitor of preadipocyte differentiation has been desired.
[0005]
[Patent Document 1]
JP-A-6-293796 [Patent Document 2]
JP 2000-37738 A [Patent Document 3]
JP-A-11-130656
[Problems to be solved by the invention]
An object of the present invention is to provide an effective and highly safe preadipocyte differentiation inhibitor, an antiobesity agent, an agent for improving cellulitis, and a food, a medicine and a cosmetic containing the same, which have no fear of side effects. It is in.
[0007]
[Means for Solving the Problems]
The present inventors have found a strong activity of inhibiting preadipocyte differentiation in certain mushrooms and plants, and have completed the present invention.
That is, the present invention
1. Kawatake mushroom, Valeriana officinalis, Uwamasana, Paschaka, Paiko, Agrayaho, Gajutsu, Chamomile, Kumazasa, Guava leaf, Caffa lime, Juniper berry, Nutmeg, Basil, Mace, Lemongrass, Rosemary, Persimmon leaf, Gymnema sylvestre, Aoyama willow, Mushrooms consisting of lemon verbena, a preadipocyte differentiation inhibitor comprising at least one selected from the group of plant or plant parts,
2.1 mushrooms, plants or adipocyte fat accumulation inhibitor comprising at least one selected from plant parts,
3.1 an anti-obesity agent comprising at least one selected from the group consisting of mushrooms, plants or plant parts (excluding Kumazasa, guava leaves and Gymnema sylvestre);
4. Kumazasa, guava leaves or gymnema sylvester as a preadipocyte differentiation inhibitor, anti-obesity composition,
5.1 The cellulitis improving agent containing at least one selected from the group consisting of mushrooms, plants and plant parts according to 5.1.
6.1 Foods containing any of the agents or compositions of 1 to 5,
A medicament containing any of the agents or compositions of 7.1 to 5, and a cosmetic containing any of the agents or compositions of 8.1 to 5,
About.
[0008]
BEST MODE FOR CARRYING OUT THE INVENTION
The mushrooms used in the present invention may be Coriolus versicolor (L .: Fr.) Quel, and the plants may be Valeriana fauriei, Jawaranda copaia, Geranium geranium and Geranian geranium Chenopodium ambrosioides), Agurayaho (Berberis vulgaris), zedoary (Curcuma zeodaris), chamomile (matricaria chamomilla), Sasa (Sasa veitchii), guava leaves (Psidium guajava L.), Kaffa lime (Citrus hystrix), juniper berry (Juniperus commun is), nutmeg (Myristica fragrans), basil (Ocimum basilicum), mace (Myristica fragrans), lemongrass (Cymbopogon citrastus), rosemary (Rosmarinus officinalis), rosemary (Rosmarinus officinis) Cyclocarina paliurus and lemon verbena can be used, and may be those usually used as food or an extract extracted using a suitable solvent.
[0009]
Coriolus versicolor (L .: Fr.) Quel is a basidiomycete and a mushroom belonging to the family Sarcodonaceae, and is widely distributed from the subtropical to the subarctic. The complex polysaccharide isolated from the cultured mycelium of this fungus was found to have antitumor activity, and has been clinically applied.
Valeriana fauriei is a perennial dicotyledonous plant belonging to the family Oleoptera, distributed from Hokkaido to Kyushu, Sakhalin, Korea, and China. The root contains about 8% of essential oils, has a peculiar odor, and is used in Chinese medicine for mental instability and sedation of hysteria.
Uwasamana (Jacaranda copaia) is a tall tree of the dicotyledonous plant belonging to the family Pondaceae, and is distributed in Central America and northern South America. Details of its medicinal properties and pharmacology are unknown, but its leaves and bark contain alkaloids, catechins, steroids, phenols, saponins and tannins.
[0010]
Paschaka (Geranium dielsianum) is a dicotyledonous plant of the family Anthracaceae, and is distributed in Central and South America. Although the details of its medicinal properties and pharmacology are unknown, it is known privately to have a hypoglycemic effect and a pancreatic function-enhancing effect, and is used to assist in the treatment of diabetes.
Paiko (Chenopodium ambrosioides) is an annual plant of the dicotyledonous plant of the family Acagusaceae, and is also referred to as "Cariatasou". It is widely distributed in temperate regions of the world, and is also found in Japan. It is known for its powerful anthelmintic activity and is also used for digestive enhancement, gastritis and antiflatulence.
Agrayaho (Berberis vulgaris) is a deciduous shrub of dicotyledonous plants of the barberry family, and is also called as barberry. Distributed from Europe to Central Asia, the fruits were edible and cultivated. In Europe, it is used as a folk medicine for chronic indigestion, constipation, healthy stomach, kidney stones, etc.
[0011]
Gejutsu (Curcuma zeodaris) is a perennial monocotyledonous plant of the ginger family. It is widely cultivated in tropical and subtropical areas from India to Southeast Asia. It is used as a stomach and expectorant in Chinese medicine.
Chamomile (Matricaria chamomilla) is a dicotyledonous plant of the Asteraceae family, distributed from Europe to West Asia, and also cultivated for medicinal purposes. In Europe, it is used as tea and as a folk medicine for anti-inflammatory, carminative, stomach, sweating and mental instability.
Kumazasa is a monocotyledonous plant belonging to the Poaceae family and is a special product of Japan, which grows naturally and is often planted for ornamental use. The details of its medicinal properties and pharmacology are unknown, but the leaves are used as a folk medicine for stomachic, diabetes and hypertension.
[0012]
Guava leaves (Psidium guajava L.) are evergreen shrubs of dicotyledonous plants of the family Myrtaceae, and are also called bunjirou. Tropical America is distributed from the tropical zone of origin to the subtropical zone. The fruit is eaten raw and is mainly used as juice. There is a habit of using leaves as tea, and it has recently been shown to be effective for hypertension.
Kaffa lime (Citrus hystrix) is a shrub of dicotyledonous plants of the Rutaceae family, and is also called Swangi or Kaffir lime. Distributed in tropical Asia. The fruit is yellow-ripened, has a lot of juice, and has strong acidity and bitterness. Used as a condiment.
Juniper berry (Juniperus communis) is a tall tree of a gymnosperm of the cypress family, and is also referred to as a northern squirrel or scorpion. Gin is widely distributed in the Northern Hemisphere and contains its cones. It is known to promote digestion and excrete water, and is used for diseases of the urethra.
[0013]
Nutmeg and mace (Myristica fragrans) are the seeds of evergreen tree, a dicotyledonous plant of the family Diptaceae. Nutmeg is the one except for the temporary seed coat that surrounds the seeds, and mace is the net-like vermilion temporary seed coat. Suitable for a marine climate, it grows well on tropical islands and is currently producing in Indonesia, East Africa and the West Indies. Contains essential oil components such as myristicin, pinene, eugenol, and safrole, and is widely used as a spice. In Kampo, it is used for indigestion, abdominal pain, diarrhea, etc.
Basil (Ocimum basilicum) is a dicotyledonous plant of the Labiatae family, and is also called Mebuki. It is considered to be native to tropical Asia, but is currently grown worldwide. It contains essential oil components such as estradiol, eugenol, lineole, linalool, thymol, tannin, and basil camphor, and is widely used as spices and herbs. It is also used as a medicament for antitussive, antipyretic, carminative, palpitation, constipation and gonorrhea.
[0014]
Lemongrass (Cymbopogon citratus) is a monocotyledonous plant of the Poaceae family, and is also called lemon sow. It is a perennial plant native to the Indian subcontinent. It contains essential oils that emit a lemon-like aroma in the whole plant, and is grown in tropical and subtropical regions. In addition to using essential oil components such as citral as flavors, it is used as a spice and as a medicament for cold headache, stomach pain, joint pain, menstrual irregularities and anorexia.
Rosemary (Rosmarinus officinalis) is an evergreen small shrub of a dicotyledonous plant of the Labiatae family, and is also called mannenrow. Native to the Mediterranean region, rosemary oil is used as a fragrance and contains essential oils such as pinene, cineole, dragon brain, and camphor. Used in cooking as spices and herbs. Both essential oil components and whole herbs are widely used as medicinal products such as digestive aid, carminative, diuretic, antidepressant, intense, gynecological, sedative and anti-inflammatory.
[0015]
Persimmon leaf (Diospyros kaki) is a leaf of a deciduous tree of a dicotyledonous plant of the genus Oyster. It is distributed in the temperate zone of East Asia, and is currently grown as a cold-resistant persimmon fruit tree in tropical highlands and in temperate regions of Europe and the United States. Fruits are rich in sugars, pectins, carotenoids, and vitamin C and are made edible. The astringency is due to tannins, and the tannins are insolubilized by various methods and are astringently removed. The leaves contain vitamin C, such as kaempferol glycoside and quercetin glycoside, and are used as folk medicine for hypertension.
Gymnema sylvestris is a dicotyledonous plant belonging to the family Potato, and is an evergreen vine that grows in shrub forests and is distributed in southern China, Taiwan, Vietnam, India, and other tropical regions. The leaves contain a triterpene glycoside called gymnemic acid, which is known to have a sugar absorption inhibitory effect, a blood sugar increase inhibitory effect, and an anti-cariogenic effect. The alcohol extract of Gymnema leaves suppresses the increase in blood sugar caused by growth hormone or corticosteroids. In China, it is used for mastitis, trauma, and swelling.
[0016]
Qingcheng willow (Cyclocarya paliurus) is a tree of the dicotyledonous plant of the walnut family, Guangdong Province, Guangxi Zhuang Autonomous Region, Guizhou Province, Hunan Province, Hubei Province, Sichuan Province, Fujian Province, Jiangxi Province, Zhejiang Province, It grows in Anhui Province. Although the details of the pharmacology and pharmacology are unknown, it is used as a folk medicine in recent years for suppressing an increase in blood sugar level.
Lemon verbena (Lippia citriodora) is a dicotyledonous plant of the family Spruce and is an evergreen shrub distributed from the tropics to the subtropics. It is distributed in Peru, Chile and parts of Brazil in South America and is grown and used as a substitute for tea and to flavor foods. It contains essential oil components such as limonene, dipentene, cineol, citral, and methylheptenone, and is said to have a stomachic effect and is used as a digestive medicine. It is also said to have antispasmodic and tonic effects.
[0017]
As the plant, all parts such as above-ground parts such as leaves, stems, buds, flowers, woody parts, bark parts (bark) and underground parts such as roots and tubers, seeds, fruits and resins can be used.
Mushrooms, plants or their parts are dried products that have dried themselves, their crushed products, squeezed juice obtained by squeezing and extracting themselves, water or alcohol, ether, crude extracts with organic solvents such as acetone, And an extract fraction obtained by partitioning the crude extract and purifying it stepwise by various chromatographies such as column chromatography and the like. These may be used alone or in combination of two or more.
For example, an extract obtained by adding 3 L of a 99.5% ethanol extract to 1 kg of a dried plant of Valeriana fauliei and immersing at room temperature overnight may be used as it is, or may be subjected to various types of chromatography. And purified ones may be used.
[0018]
It has not been known at all that these specific mushrooms, plants, and dried or extracted plant parts have the activity of inhibiting the differentiation of preadipocytes, and new findings obtained by the present invention. It is.
The dried product or extract of the mushroom, plant, or plant part of the present invention has an excellent activity of suppressing preadipocyte differentiation, and contains a fat accumulation inhibitor, an antiobesity agent, a cellulitis improving agent, and the like. It can be used as food, medicine and cosmetics.
Manufacture mushrooms, plants, and dried or extracted plant parts as preadipocyte differentiation inhibitors, fat accumulation inhibitors, antiobesity agents, cellulitis improving agents, and foods, medicaments and cosmetics containing them be able to.
[0019]
The method of application as a medicament can be either oral administration or parenteral administration. Upon administration, the active ingredient can be mixed with a solid or liquid nontoxic pharmaceutical carrier suitable for administration methods such as oral administration, rectal administration and injection, and administered in the form of a conventional pharmaceutical preparation. Such preparations include, for example, solid preparations such as tablets, granules, powders and capsules, liquid preparations such as solutions, suspensions and emulsions, and lyophilized preparations. It can be prepared by conventional means. Examples of the above pharmaceutical non-toxic carrier include, for example, glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, gelatin, Examples include albumin, water, and physiological saline. Further, if necessary, conventional additives such as a stabilizer, a wetting agent, an emulsifier, a binder, and a tonicity agent can be appropriately added.
[0020]
As food, it is eaten as it is or as a health food or food material useful for treatment and prevention of cellulitis or obesity by adding various nutrients or by including it in food or drink. For example, after adding the above-mentioned appropriate auxiliaries, using conventional means, edible forms, such as granules, granules, tablets, capsules, pastes, etc., may be edible, Various foods, for example, ham, processed meat foods such as sausage, kamaboko, processed marine products such as chikuwa, bread, confectionery, butter, powdered milk, fermented dairy products, or used in addition to water, juice, milk, It may be used by adding to a beverage such as a soft drink.
[0021]
The effective dose is appropriately selected and determined depending on the patient's age, body weight, symptoms, degree of the patient, administration route, administration schedule, formulation, strength of the inhibitory activity of the material, and the like. In general, about 0.001 to 1000 mg / kg body weight per day, and in the case of a hot water extract of guamana (Jacaranda copaia), it is about 1 to 300 mg / kg body weight per day. Is also good.
[0022]
Further, when used as a cosmetic or a cosmetic material, for example, a dried product or extract of Coriolus versicolor (L .: Fr.) Quel is added to wheat germ oil or olive oil to inhibit preadipocyte differentiation. The composition can be used as a cosmetic material. The amount added is not particularly limited, but as an example, is 0.1% by mass or more and 60% by mass or less, preferably 0.5% by mass or more and 50% by mass with respect to the weight of wheat germ oil or olive oil. % Or less is appropriate.
In addition, a cosmetic having a preadipocyte differentiation action can be produced by directly using it as a cosmetic component.
[0023]
The cosmetic is not particularly limited, but from the functional aspect, for example, a face or body emulsion, a cosmetic solution, a cream, a lotion, an essence, a pack, a sheet, and the like are preferable.
Such a cosmetic can be manufactured according to a conventional method. The amount of addition in the cosmetic is not particularly limited, but as an example, about 0.01% by mass to 20% by mass of the total weight of the cosmetic is appropriate.
Since the plant of the present invention is a natural product, its toxicity is low. For example, even if a hot water extract of rosemary (Rosmarinus officinalis) is orally administered to rats over a long period of 100 mg / kg for 100 days every day, No deaths were observed and no change in body weight was observed.
[0024]
【Example】
Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited thereto.
[0025]
[Pharmacological test]
Preparation of Sample 1: Approximately 1200 (Coriolus versicolor) (Coriolus versicolor) were pulverized by a mixer and immersed in 5 L of 80% ethanol-water for 3 days. The filtrate obtained by filtration under reduced pressure was concentrated by an evaporator to obtain 16.6 g of a crude extract as a brown oil. This crude extract was partitioned between 400 mL of water and 400 mL of ethyl acetate. The obtained aqueous layer was further partitioned twice with 400 mL of ethyl acetate, and all the ethyl acetate layers were collected and concentrated by an evaporator to obtain 1.21 g of ethyl acetate-soluble matter as a brown oil. This was used as a sample for measuring fat accumulation.
[0026]
Preparation of Sample 2: Plants Valerian (Valeriana fauriei), Uwamasamana (Jacaranda copaia), Pasuchaka (Geranium dielsianum), Paiko (Chenopodium ambrosioides), Agurayaho (Berberis vulgaris), zedoary (Curcuma zeodaris), chamomile (Matricaria chamomilla), Sasa veitchii ( Sasa veitchii, guava leaves (Psidium guajava L.), kaffir lime (Citrus hystrix), juniper berries (Juniperus communis), nutmeg (Myristica fragrans), basil (Ocium umium) ristica fragrans, lemongrass (Cymbopogon citratus), rosemary (Rosmarinus officinalis), persimmon leaves (Diospyros kaki), gymne sylvestris (Gymnemar sylvestris, Gymnemar sylvestris) After adding 300 ml of 80% ethanol-water to each 100 g and immersing for 3 days, the filtrate was freeze-dried to obtain each of the ethanol-extracted and dried products 520, 780, 10560, 820, 4040, 1260, 1160, 520, 1200, 1620, 7500, 5000, 1240, 17600, 2160, 6440, 2920, 4840, 900, 180 It was obtained mg. This was used as a sample for measuring fat accumulation.
[0027]
[Measurement of preadipocyte fat accumulation rate]
In two 24-well microplates, mouse preadipocytes (3T3-L1) are present in 1 mL of culture medium (DMEM containing 10% fetal calf serum (glucose concentration 4500 mg / mL)) at 5% CO 2 until they reach confluence. The cells were cultured at 37 ° C for 7 days. In the same manner for both sheets, the medium was removed by suction, and 1 μM dexamethasone, 10 μg / mL insulin and 0.5 mM 3-isobutyl-1-methylxanthine were added to a differentiation-inducing medium (DMEM containing 10% fetal bovine serum (glucose concentration 4500 mg / mL)). (Dissolved medium) was replaced with 1.5 mL, and then 7.5 μL of a methanol solution of the sample was added. At this time, wells which were not replaced with the differentiation induction medium and wells to which only methanol was added instead of the sample solution were prepared as controls. The cells were cultured at 37 ° C. for 6 days in the presence of 5% CO 2 , one of which was used for measuring fat mass, and the other was used for measuring viability.
[0028]
For one piece of fat mass measurement, 100 μL of 2% Triton-X100 was added to each well, left standing for 30 minutes, then applied a sealing tape (manufactured by Asahi Techno Glass) and sonicated for 1 minute on an ultrasonic cleaner. Was. 20 μL of each well content was collected in a 96-well microplate, 100 μL of a triglyceride G-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) coloring reagent was added thereto, and the mixture was cultured at 37 ° C. for 30 minutes, followed by absorbance (550 nm) with a plate reader. Was measured. The ratio of the absorbance of the sample-added group to the absorbance of the sample-free group was determined as a percentage, and was defined as a fat accumulation rate. Table 1 shows the fat accumulation rates of the obtained samples. It can be seen that the lower the fat accumulation rate, the more the adipocyte differentiation is suppressed.
[0029]
[Safety test]
To one well for measuring the survival rate, 20 μL of a cell counting kit (manufactured by Dojindo Laboratories) was added to each well, and after culturing at 37 ° C. for 4 hours, the absorbance (450 nm) was measured with a plate reader. The ratio of the absorbance of the sample-added group to the absorbance of the sample-free group was determined as a percentage, and was defined as the cell viability. Table 1 shows the cell viability of each sample obtained. It can be seen that any mushroom, plant or plant part has no problem with safety.
[0030]
[Table 1]
[0031]
Formulation Example 1
[Manufacture of tablets]
Using the ethanol extract of lemon verbena (Lippia citridorora) obtained in the sample preparation for the pharmacological test, tablets having the following composition were produced according to a conventional method.
[0032]
Formulation Example 2
[Manufacture of juice]
Using the ethanol extract of chamomile (Matricaria chamomilla) obtained in the sample preparation for the pharmacological test, juice having the following composition was produced according to a conventional method.
[0033]
Formulation Example 3
[Manufacture of face cream]
Using an ethanol extract of Juniperus communis obtained in [Sample preparation] of the pharmacological test, a face cream having the following composition was produced according to a conventional method.
[0034]
【The invention's effect】
The mushrooms, plants, and plant parts of the present invention strongly contribute to the suppression and improvement of fat accumulation and obesity because they strongly suppress the differentiation of preadipocytes, and the honeycomb resulting from local fat cell hypertrophy. It is effective in preventing and treating inflammation.
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