JP6159918B2 - Hyaluronidase inhibitors and methods for inhibiting hyaluronidase activity - Google Patents
Hyaluronidase inhibitors and methods for inhibiting hyaluronidase activity Download PDFInfo
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Description
本発明は、ヒアルロニダーゼの活性阻害作用を有する新規のヒアルロニダーゼ活性阻害剤及びその応用品に関する。 The present invention relates to a novel hyaluronidase activity inhibitor having a hyaluronidase activity inhibitory action and applications thereof.
ヒアルロン酸は、関節および真皮表層などに多く存在する成分であり、関節の潤滑、皮膚の柔軟化、保水性などに関与している物質である。
ヒアルロニダーゼは、ヒアルロン酸を分解することにより、結合組織の再構築における細胞活動の一環を担う酵素である。ヒアルロニダーゼは、加齢や炎症時に活性化され、これが過剰に作用するとヒアルロン酸の分解量が増加する。ヒアルロニダーゼが活性化しすぎると、ヒアルロン酸の合成より、分解される速度が大きくなり、結果として、炎症反応の亢進や、皮膚のシワ、関節痛等の原因となる。また、ヒアルロニダーゼはヒスタミンの放出に関与しており、花粉症等のアレルギーの発生にも関わっている。
Hyaluronic acid is a component that is abundant in the joint and dermis surface and is a substance involved in joint lubrication, skin softening, water retention and the like.
Hyaluronidase is an enzyme that plays a part in cellular activities in the reconstruction of connective tissue by degrading hyaluronic acid. Hyaluronidase is activated during aging and inflammation, and when it acts excessively, the amount of hyaluronic acid decomposed increases. When hyaluronidase is activated too much, the rate of degradation is greater than the synthesis of hyaluronic acid, resulting in an increased inflammatory response, skin wrinkles, joint pain and the like. Hyaluronidase is also involved in the release of histamine, and is also involved in the occurrence of allergies such as hay fever.
そのため、ヒアルロニダーゼの酵素活性を阻害するヒアルロニダーゼ阻害剤は、炎症、皮膚の老化、関節痛等のヒアルロン酸の過剰分解に起因する疾患の予防や改善、アレルギー性疾患の予防や改善への利用が期待されている。
これまでにヒアルロニダーゼの活性阻害作用を有する成分として、様々な報告がなされている。例えば、特許文献１には、ブドウの抽出物を有効成分にすること、特許文献２には、低分子化サイリウムシードガム、特許文献３には、ワイルドタイム及びホップの抽出物がヒアルロニダーゼ阻害剤として報告されている。
Therefore, hyaluronidase inhibitors that inhibit the enzymatic activity of hyaluronidase are expected to be used for the prevention and improvement of diseases caused by excessive degradation of hyaluronic acid such as inflammation, skin aging and joint pain, and prevention and improvement of allergic diseases. Has been.
So far, various reports have been made as components having an inhibitory action on hyaluronidase activity. For example, Patent Document 1 includes grape extract as an active ingredient, Patent Document 2 includes low molecular weight psyllium seed gum, and Patent Document 3 includes wild time and hop extracts as hyaluronidase inhibitors. It has been reported.
また、ヒアルロニダーゼ阻害活性を有する麹菌発酵物として、特許文献４には大豆、小麦、柑橘類、果実及びこれらの加工品の麹菌発酵物、特許文献５には大豆胚芽の麹菌発酵物が開示されている。 Further, as a koji mold fermented product having hyaluronidase inhibitory activity, Patent Document 4 discloses a koji mold fermented product of soybeans, wheat, citrus fruits, fruits and processed products thereof, and Patent Document 5 discloses a koji mold fermented product of soybean germ. .
上述の特許文献４，５に開示されているように、麹菌発酵物の中にはヒアルロニダーゼ阻害活性があることが知られている。一方、麹菌発酵物は、発酵対象となる原料によって含有される成分が異なることが知られており、実際にどの成分が有効であるかよく分かっていないのが実状である。
かかる状況下、本発明の目的は、従来報告されていない麹菌発酵物由来のヒアルロニダーゼ活性阻害剤およびその応用品を提供することである。
As disclosed in Patent Documents 4 and 5 described above, it is known that some fermented koji molds have hyaluronidase inhibitory activity. On the other hand, fermented koji molds are known to contain different components depending on the raw material to be fermented, and it is actually not known which components are actually effective.
Under such circumstances, an object of the present invention is to provide a hyaluronidase activity inhibitor derived from a koji mold fermented product that has not been reported so far, and an application product thereof.
本発明者は、上記課題を解決すべく鋭意研究を重ねた結果、白麹菌(Aspergillus kawachii)、黒麹菌（Aspergillus awamori）及び黄麹菌（Aspergillus oryzae）から選択される少なくとも１種を繁殖させた米麹から得られた加工物が、ヒアルロニダーゼ活性阻害を有することを見出した。 As a result of intensive studies to solve the above problems, the present inventor has bred at least one species selected from Aspergillus kawachii, Aspergillus awamori, and Aspergillus oryzae. It was found that the processed product obtained from cocoon has hyaluronidase activity inhibition.
すなわち、本発明は、以下の発明に係るものである。
＜１＞ 白麹菌(Aspergillus kawachii)、黒麹菌（Aspergillus awamori）及び黄麹菌（Aspergillus oryzae）から選択される少なくとも１種を繁殖させた米麹加工物を含有するヒアルロニダーゼ阻害剤。
＜２＞ 前記米麹加工物が、前記米麹の乾燥物である前記＜１＞に記載のヒアルロニダーゼ阻害剤。
＜３＞ 前記米麹加工物が、前記米麹と、水、エタノール及び１，３−ブチレングリコールから選択される１種以上を主溶媒として含有する抽出溶媒とを接触させ、前記米麹に含有される成分を抽出して得られる抽出物である前記＜１＞に記載のヒアルロニダーゼ阻害剤。
＜４＞ 前記抽出溶媒が、水を主体とする溶媒である前記＜３＞に記載のヒアルロニダーゼ阻害剤。
＜５＞ 前記＜１＞から＜４＞のいずれかに記載のヒアルロニダーゼ阻害剤を配合してなる化粧料組成物。
＜６＞ 前記＜１＞から＜４＞のいずれかに記載のヒアルロニダーゼ阻害剤を配合してなる機能性食品。
That is, the present invention relates to the following inventions.
<1> A hyaluronidase inhibitor containing a processed rice bran product obtained by breeding at least one selected from Aspergillus kawachii, Aspergillus awamori, and Aspergillus oryzae.
<2> The hyaluronidase inhibitor according to <1>, wherein the processed rice bran is a dried product of the rice bran.
<3> The rice bran processed product is brought into contact with the rice bran and an extraction solvent containing, as a main solvent, one or more selected from water, ethanol and 1,3-butylene glycol, and contained in the rice bran. The hyaluronidase inhibitor according to <1>, wherein the hyaluronidase inhibitor is an extract obtained by extracting the components to be extracted.
<4> The hyaluronidase inhibitor according to <3>, wherein the extraction solvent is a solvent mainly composed of water.
<5> A cosmetic composition comprising the hyaluronidase inhibitor according to any one of <1> to <4>.
<6> A functional food comprising the hyaluronidase inhibitor according to any one of <1> to <4>.
本発明によれば、生体に対する安全性が高く、ヒアルロニダーゼ活性阻害に優れたヒアルロニダーゼ活性阻害剤及びその応用品が提供される。 ADVANTAGE OF THE INVENTION According to this invention, the safety | security with respect to a biological body is high, and the hyaluronidase activity inhibitor excellent in hyaluronidase activity inhibition and its application product are provided.
以下、本発明について例示物等を示して詳細に説明するが、本発明は以下の例示物等に限定されるものではなく、本発明の要旨を逸脱しない範囲において任意に変更して実施できる。なお、本明細書において、「〜」という表現を用いた場合、その前後の数値または物理値を含む意味で用いることとする。 Hereinafter, the present invention will be described in detail with reference to examples and the like, but the present invention is not limited to the following examples and the like, and can be arbitrarily modified and implemented without departing from the gist of the present invention. In addition, in this specification, when the expression “to” is used, it is used in a sense including numerical values or physical values before and after that.
＜ヒアルロニダーゼ活性阻害剤＞
本発明は、白麹菌(Aspergillus kawachii)、黒麹菌（Aspergillus awamori）及び黄麹菌（Aspergillus oryzae）から選択される少なくとも１種を繁殖させた米麹加工物を含有するヒアルロニダーゼ活性阻害剤（以下、「本発明のヒアルロニダーゼ阻害剤」、又は「本発明の阻害剤」と記載する場合がある。）に関する。
<Hyaluronidase activity inhibitor>
The present invention relates to an inhibitor of hyaluronidase activity containing a processed rice bran product obtained by breeding at least one selected from Aspergillus kawachii, Aspergillus awamori, and Aspergillus oryzae (hereinafter, “ It may be referred to as “the hyaluronidase inhibitor of the present invention” or “the inhibitor of the present invention”).
本発明の阻害剤は、米に麹菌を繁殖させた米麹のうち、麹菌として白麹菌(Aspergillus kawachii)、黒麹菌（Aspergillus awamori）及び黄麹菌（Aspergillus oryzae）から選択される少なくとも１種を繁殖させた下記で説明する米麹加工物を使用していることに特徴があり、優れたヒアルロニダーゼ阻害作用を発現する。
以下、本発明の阻害剤について詳細に説明する。
The inhibitor of the present invention propagates at least one selected from Aspergillus kawachii, Aspergillus awamori, and Aspergillus oryzae as rice koji out of rice koji that has been bred with rice. It is characterized by using the processed rice bran described below and exhibits an excellent hyaluronidase inhibitory action.
Hereinafter, the inhibitor of the present invention will be described in detail.
（米麹）
本発明の阻害剤に含有される米麹は、麹菌として白麹菌(Aspergillus kawachii)を繁殖させた米麹（以下、「米麹（白麹菌）」と記載する場合がある。）または、黒麹菌（Aspergillus awamori）を繁殖させた米麹（以下、「米麹（黒麹菌）」と記載する場合がある。）、及び黄麹菌（Aspergillus oryzae）を繁殖させた米麹（以下、「米麹（黄麹菌）」と記載する場合がある。）が挙げられる。なお、以下、米麹（白麹菌）、米麹（黒麹菌）及び米麹（黄麹菌）を総称して「本発明の米麹」と記載する場合がある。
(Malted rice)
The rice bran contained in the inhibitor of the present invention is a rice bran obtained by breeding aspergillus aspergillus (Aspergillus kawachii) (hereinafter may be referred to as “rice bran (bacilli))” or black koji mold. (Hereinafter sometimes referred to as “rice koji (black koji mold)”) and rice koji (Aspergillus oryzae) that has been bred (Aspergillus awamori) May be described as "Sanchobacteria japonica"). Hereinafter, rice bran (white koji mold), rice koji (black koji mold), and rice koji (yellow koji mold) may be collectively referred to as “rice koji of the present invention”.
黒麹菌（Aspergillus awamori）は、焼酎の製造に使用されている麹菌であり、白麹菌(Aspergillus kawachii)は、黒麹菌（Aspergillus awamori）の突然変異株であり、これも焼酎の製造に使用されている。また、黄麹菌（Aspergillus oryzae）は、清酒製造に使用される麹菌である。本発明の米麹加工物は、いずれもヒアルロニダーゼ阻害作用を有する。 Aspergillus awamori is a koji mold used for the production of shochu, and Aspergillus kawachii is a mutant strain of Aspergillus awamori, which is also used for the production of shochu. Yes. In addition, Aspergillus oryzae is a koji mold used for sake production. The rice bran processed product of the present invention has a hyaluronidase inhibitory action.
米麹の原料である米類としては、玄米、ウルチ米、精白米等が挙げられる。これらは必要に応じて、適当な大きさに粉砕して使用してもよい。米類は、固めに炊く、あるいは蒸したのちに、白麹菌、黒麹菌及び黄麹菌から選択される少なくとも１種を繁殖させて本発明に係る米麹とする。
好適な一例を挙げると、精白米を水で精米した後、冷水に浸漬する。その後、余計な水切りを行い、精白米を蒸しあげる。蒸しあがった精白米の水分を飛ばし、麹菌を混ぜ込んでいく。次に麹菌を混ぜた精白米を３５〜４０℃で１８時間保温し、その後、麹菌が付着した精白米を均一に広げ３４℃で６時間保温する。これを２回繰り返し、麹を製造する。
麹菌としては、白麹菌、黒麹菌及び黄麹菌から選択される少なくとも１種を使用できる。
Examples of rice that is a raw material for rice bran include brown rice, uruchi rice, and polished rice. These may be used after being pulverized to an appropriate size as required. After the rice is cooked or steamed, at least one selected from white koji mold, black koji mold and yellow koji mold is propagated to obtain rice koji according to the present invention.
As a preferred example, polished rice is polished with water and then immersed in cold water. After that, drain extra water and steam the polished rice. Drain the water from the steamed polished rice and mix the koji mold. Next, the polished rice mixed with koji mold is kept warm at 35 to 40 ° C. for 18 hours, and then the polished rice to which the koji mold is adhered is spread uniformly and kept at 34 ° C. for 6 hours. This is repeated twice to produce cocoons.
As the koji mold, at least one selected from white koji mold, black koji mold and yellow koji mold can be used.
（米麹加工物）
本発明に係る米麹加工物（以下、「本発明の米麹加工物」と記載する場合がある。）における「加工」の種類は、本発明の米麹加工物の効果を損なわないものであるならば、適宜のものが選択でき、例えば、抽出、粉砕、乾燥などが挙げられる。また、本発明の米麹加工物における「加工物」の形態としては、後述で説明する溶媒抽出物と、本発明の米麹を乾燥物にしたものが好適である。本発明の米麹加工物は、ヒアルロニダーゼ阻害作用を有すると共に、人体に対する毒性や刺激性が少ない。そのため、化粧料組成物、機能性食品などの用途に使用することができる。
(Processed rice bran)
The type of “processing” in the processed rice bran according to the present invention (hereinafter sometimes referred to as “the processed rice bran of the present invention”) does not impair the effect of the processed rice bran of the present invention. If there is, an appropriate one can be selected, and examples thereof include extraction, pulverization, and drying. Moreover, as a form of the “processed product” in the processed rice bran product of the present invention, a solvent extract described later and a dried product of the rice bran of the present invention are suitable. The processed rice bran of the present invention has a hyaluronidase inhibitory action and is less toxic and irritating to the human body. Therefore, it can be used for applications such as cosmetic compositions and functional foods.
なお、本発明の阻害剤によるヒアルロニダーゼ阻害作用は、当該阻害剤が含有する米麹加工物の形態や量に依存し、ヒアルロニダーゼ阻害率が３０％以上（好適には４０％以上）となる範囲で決定される。 The inhibitory action of hyaluronidase by the inhibitor of the present invention depends on the form and amount of processed rice bran contained in the inhibitor, and the hyaluronidase inhibition rate is 30% or more (preferably 40% or more). It is determined.
（乾燥物）
本発明に係る米麹の乾燥物（以下、単に「乾燥物」と記載する場合がある。）とは、本発明の米麹から水分を抜き取り乾燥させることにより得られるもののことである。この乾燥の方法や乾燥条件は、本発明の米麹加工物の効果を損なわないような一般的なものを適宜用いることができる。例えば、真空乾燥、天日乾燥、加熱乾燥、フリーズドライ、ドライヤーの温風を用いるなど公知の乾燥方法を使用すればよい。
(Dry product)
The dried rice bran according to the present invention (hereinafter sometimes simply referred to as “dried product”) is obtained by extracting moisture from the rice bran of the present invention and drying it. As the drying method and drying conditions, general methods that do not impair the effects of the processed rice bran product of the present invention can be used as appropriate. For example, a known drying method such as vacuum drying, sun drying, heat drying, freeze drying, or using warm air from a dryer may be used.
得られた乾燥物は、粉末にして用いてもよい。粉末にすることで汎用性が向上し、機能性食品、化粧料組成物の原料として手軽に使用することができる。乾燥物を粉砕して粉末にする場合の粉砕方法としては、特に限定はなく、公知の粉砕器を使用すればよい。粉末の粒径は、その用途によって適宜決定できる。 The obtained dried product may be used as a powder. By using powder, versatility is improved and it can be easily used as a raw material for functional foods and cosmetic compositions. There is no particular limitation on the pulverization method when the dried product is pulverized into powder, and a known pulverizer may be used. The particle size of the powder can be appropriately determined depending on its use.
（溶媒抽出物）
本発明の阻害剤において、本発明の米麹の溶媒抽出物（以下、単に「抽出物」と記載する場合がある。）とは、抽出対象となる本発明の米麹を溶媒に接触させることにより、当該米麹に含まれる有効成分を抽出した形態のものを総括した概念である。本発明の阻害剤における抽出物は、具体的には、本発明の米麹を溶媒抽出して得られる抽出液、該抽出液の希釈液若しくは濃縮液、又はこれらの粗精製物若しくは精製物のいずれもが含まれる。また、液状の抽出物を乾燥して得られる乾燥物も、本発明における抽出物に該当するものとする。
(Solvent extract)
In the inhibitor of the present invention, the solvent extract of rice bran of the present invention (hereinafter sometimes simply referred to as “extract”) refers to bringing the rice bran of the present invention to be extracted into contact with a solvent. Thus, it is a concept that summarizes the extracted forms of the active ingredients contained in the rice bran. The extract in the inhibitor of the present invention is specifically an extract obtained by solvent extraction of the rice bran of the present invention, a diluted solution or a concentrated solution of the extract, or a crudely purified product or a purified product thereof. Both are included. A dried product obtained by drying a liquid extract also corresponds to the extract in the present invention.
抽出物は、乾燥物を除くいずれの場合においても、必要に応じて、不溶分を除去するために、透析、限外ろ過、ろ過、カラムクロマトグラフィー等による前処理を行ってもよい。ろ過による除去の場合には、必要に応じて、不純物を除去するために活性炭、ベントナイト、セライト等の吸着剤やろ過助剤を添加してもよい。特に抽出液の状態で用いる場合には、メンブレンフィルター等による除菌ろ過を併せて行うことが好ましい。 In any case except the dried product, the extract may be pretreated by dialysis, ultrafiltration, filtration, column chromatography or the like, as necessary, in order to remove insoluble matter. In the case of removal by filtration, an adsorbent such as activated carbon, bentonite, or celite or a filter aid may be added as necessary to remove impurities. In particular, when used in the state of an extract, it is preferable to perform sterilization filtration using a membrane filter or the like.
抽出物は、必要に応じて任意の公知の方法で精製してもよく、必要に応じて、医薬および食品分野において許容される塩、誘導体または溶媒和物等に変換してもよい。 The extract may be purified by any known method as necessary, and may be converted into a salt, derivative, solvate or the like that is acceptable in the pharmaceutical and food fields, if necessary.
抽出物を溶媒抽出で得る場合、抽出溶媒としては、本発明の米麹に含有されるヒアルロニダーゼ阻害作用を発現する有効成分を抽出できるものであればよい。具体例としては、水、メタノール、エタノール、プロピルアルコール、イソプロピルアルコール等の炭素数１〜５の低級アルコール；アセトン、メチルエチルケトン等の低級脂肪族ケトン；１，３−ブチレングリコール、プロピレングリコール、グリセリン等の炭素数２〜５の多価アルコールなどが挙げられる。なお、抽出溶媒として使用し得る水には、精製水、イオン交換水、生理食塩水、リン酸緩衝液、リン酸緩衝生理食塩水等も含まれる。
これらの抽出溶媒は単独又はこれら２種以上の混合物として使用することができ、２種以上の溶媒の混合液を抽出溶媒として使用する場合、その混合比は適宜調整することができる。
When the extract is obtained by solvent extraction, the extraction solvent may be any one that can extract an active ingredient that expresses the hyaluronidase inhibitory action contained in the rice bran of the present invention. Specific examples include lower alcohols having 1 to 5 carbon atoms such as water, methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; 1,3-butylene glycol, propylene glycol, glycerin, and the like. Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms. The water that can be used as the extraction solvent includes purified water, ion exchange water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.
These extraction solvents can be used alone or as a mixture of two or more thereof. When a mixture of two or more solvents is used as the extraction solvent, the mixing ratio can be appropriately adjusted.
なお、抽出溶媒には、本発明の効果を損なわない範囲で添加剤を含んでいてもよい。例えば、ｐＨ調整剤、粘度調整剤などが挙げられる。 The extraction solvent may contain an additive as long as the effects of the present invention are not impaired. For example, a pH adjuster, a viscosity adjuster, etc. are mentioned.
本発明に係る抽出物において、本発明の米麹と、抽出溶媒とを接触させ、前記米麹に含有される成分を抽出して得られる抽出物であることが好ましい。
抽出溶媒としては、水、エタノール及び１，３−ブチレングリコールから選択される１種以上を主溶媒として含有する抽出溶媒であることが好ましい。ここで、「主溶媒」とは溶媒全量の５０体積％以上（１００体積％含む）を占める溶媒を意味する。
化粧料組成物や機能性食品として配合する観点では、水を主溶媒とすることが好ましい。水以外の溶媒としては、上記の溶媒を使用することができ、抽出効率や、目的とする化粧料組成物、機能性食品等の応用用途等を考慮して適宜選択される。
The extract according to the present invention is preferably an extract obtained by bringing the rice bran of the present invention into contact with an extraction solvent and extracting the components contained in the rice bran.
The extraction solvent is preferably an extraction solvent containing, as a main solvent, one or more selected from water, ethanol, and 1,3-butylene glycol. Here, the “main solvent” means a solvent occupying 50% by volume (including 100% by volume) of the total amount of the solvent.
From the viewpoint of blending as a cosmetic composition or functional food, water is preferably used as the main solvent. As the solvent other than water, the above-mentioned solvents can be used, and are appropriately selected in consideration of the extraction efficiency, the intended cosmetic composition, the application use of functional foods, and the like.
本発明に係る抽出物として、本発明の米麹と水の混合物をろ過したもの、本発明の米麹と水の混合物を加温後濾過したものが好適な一例として挙げられる。また、本明細書において、米麹（白麹菌）、米麹（黒麹菌）及び米麹（黄麹菌）の水抽出物を、それぞれ白麹水抽出物、黒麹水抽出物及び黄麹水抽出物と記載する。 Preferred examples of the extract according to the present invention include those obtained by filtering the rice bran and water mixture of the present invention and those obtained by heating and filtering the rice bran and water mixture of the present invention. Moreover, in this specification, the rice bran (white koji mold), the rice koji (black koji mold), and the rice koji (yellow koji mold) aqueous extract are respectively white birch water extract, black koji water extract and yellow koji water extract. It is described as a thing.
本発明の米麹に対する抽出溶媒の量は特に制限はないが、通常、米麹に対して重量比で３〜１００倍量程度である。抽出溶媒が水の場合には、米麹に対して重量比で５〜２０倍量であることが好ましい。 Although there is no restriction | limiting in particular in the quantity of the extraction solvent with respect to the rice bran of this invention, Usually, it is about 3-100 times amount by weight ratio with respect to a rice bran. When the extraction solvent is water, the amount is preferably 5 to 20 times the weight of rice bran.
本発明の米麹から溶媒抽出物を抽出する方法は特に限定されず、常法に従って行なれる。例えば、米麹と、抽出溶媒とを互いに充分に攪拌し混合後、米麹から溶媒中に、有効成分が十分に抽出されるまで一定期間静置する。抽出時間は、抽出溶媒の種類や、米麹と抽出溶媒との割合を考慮し適宜選択されるが、抽出溶媒が水の場合は１〜３時間である。
また、抽出物に含まれる残渣を取り除くため、濾過や遠心分離を行ってもよい。また、得られた抽出液はそのまま利用してもよいが、常法に従って希釈、濃縮、乾燥、精製等の処理を施してもよい。
加温により米麹のデンプンやタンパク質などが分解され豊富な栄養成分（アミノ酸・糖など）を抽出液中に含有させることができる。なお、抽出操作の温度としては、本発明の効果であるヒアルロニダーゼ阻害活性を損なわない限りは適宜のものを選択することができる。また、必要に応じて抽出物の割合を高めるため、減圧濃縮や凍結乾燥により溶媒除去してもよい。
The method for extracting the solvent extract from the rice bran of the present invention is not particularly limited, and can be performed according to a conventional method. For example, the rice bran and the extraction solvent are sufficiently stirred and mixed with each other, and then allowed to stand for a certain period until the active ingredient is sufficiently extracted from the rice bran into the solvent. The extraction time is appropriately selected in consideration of the type of extraction solvent and the ratio of rice bran and extraction solvent, but is 1 to 3 hours when the extraction solvent is water.
Moreover, in order to remove the residue contained in the extract, filtration or centrifugation may be performed. Moreover, although the obtained extract may be used as it is, it may be subjected to treatments such as dilution, concentration, drying and purification according to a conventional method.
By heating, starch, protein, etc. of rice bran are decomposed and abundant nutritional components (amino acids, sugars, etc.) can be contained in the extract. In addition, as temperature of extraction operation, unless the hyaluronidase inhibitory activity which is the effect of this invention is impaired, an appropriate thing can be selected. Moreover, in order to raise the ratio of an extract as needed, you may remove a solvent by vacuum concentration or freeze-drying.
また、本発明のヒアルロニダーゼ阻害剤は、米麹の溶媒抽出物、希釈用溶媒以外にも本発明の効果を損なわない範囲で、防腐剤、ｐＨ調整剤等の任意の成分を含有していてもよい。任意成分の配合割合は、その目的に応じて適宜選択して決定することができる。 Further, the hyaluronidase inhibitor of the present invention may contain any components such as preservatives, pH adjusters and the like within the range not impairing the effects of the present invention other than the rice bran solvent extract and the dilution solvent. Good. The blending ratio of the optional components can be determined by appropriately selecting according to the purpose.
本発明の阻害剤としては、上記の米麹加工物である溶媒抽出物を、原液をそのまま用いても、濃縮して濃縮液として用いてもよく、原液あるいは濃縮液を希釈溶媒に溶解して使用してもよい。この希釈溶媒としては、ヒアルロニダーゼ阻害作用を損なわないものが選択され、水、エチルアルコール、イソプロピルアルコール、グリセリン、プロピレングリコール、１，３−ブチレングリコール等を例示することができる。 As the inhibitor of the present invention, the above-described solvent extract, which is a processed rice bran product, may be used as a stock solution as it is, or may be concentrated and used as a concentrate, or the stock solution or concentrate is dissolved in a diluting solvent. May be used. As the diluting solvent, a solvent that does not impair the hyaluronidase inhibitory action is selected, and water, ethyl alcohol, isopropyl alcohol, glycerin, propylene glycol, 1,3-butylene glycol and the like can be exemplified.
＜ヒアルロニダーゼ阻害剤の応用用途＞
本発明のヒアルロニダーゼ阻害剤は、ヒアルロニダーゼの活性を阻害できるので、ヒアルロニダーゼの活性が関与する疾患の予防、治療、症状の改善に寄与することができる。
本発明のヒアルロニダーゼ阻害剤を配合した組成物は、各種化粧料組成物、機能性食品等の用途に使用することができる。
<Application of hyaluronidase inhibitor>
Since the hyaluronidase inhibitor of the present invention can inhibit the activity of hyaluronidase, it can contribute to the prevention, treatment and improvement of symptoms associated with the activity of hyaluronidase.
The composition containing the hyaluronidase inhibitor of the present invention can be used for various cosmetic compositions, functional foods and the like.
ヒアルロニダーゼの活性が関与する疾患として、ヒアルロン酸分解に起因する疾患として、炎症、皮膚の老化、関節痛、リウマチ、肝疾患等が挙げられる。なお、皮膚の老化とは、皮膚のしわ、たるみ、弾力低下、水分不足等を含む概念である。 Examples of the disease involving hyaluronidase activity include inflammation, skin aging, arthralgia, rheumatism, liver disease and the like as diseases caused by hyaluronic acid degradation. Skin aging is a concept that includes wrinkles, sagging, reduced elasticity, lack of moisture, and the like.
（化粧料組成物）
本発明の化粧料組成物は、上述したヒアルロニダーゼ阻害剤を配合してなることを特徴とする。なお、本発明の化粧料組成物は、一般的な美容用途等の化粧品に使用できるほか、入浴剤やシャンプー、石鹸など皮膚を保護し、洗浄するボディーケア製品用にも使用することができる。
(Cosmetic composition)
The cosmetic composition of the present invention is characterized by comprising the above-described hyaluronidase inhibitor. In addition, the cosmetic composition of the present invention can be used for cosmetics such as general cosmetics, and can also be used for body care products that protect and wash the skin such as bathing agents, shampoos, and soaps.
本発明のヒアルロニダーゼ阻害剤を化粧料組成物に配合して用いる場合、化粧料組成物への本発明の阻害剤の配合割合は、米麹の抽出物の含有量として、化粧料組成物がヒアルロニダーゼ阻害作用を十分に発揮する範囲で適宜選択される。化粧料組成物には、慣用の化粧料基材を適宜配合し、所望の剤型とすることができる。その形態は特に制限はないが、ジェル、乳液、クリーム等の形態が挙げられる。 When the hyaluronidase inhibitor of the present invention is used in a cosmetic composition, the proportion of the inhibitor of the present invention in the cosmetic composition is the content of the extract of rice bran, and the cosmetic composition is hyaluronidase. It is appropriately selected within the range where the inhibitory action is sufficiently exhibited. In the cosmetic composition, a conventional cosmetic base material can be appropriately blended to obtain a desired dosage form. The form is not particularly limited, and examples thereof include gels, emulsions, and creams.
本発明のヒアルロニダーゼ阻害剤を化粧料組成物に用いる際の化粧料基材としては、目的とする剤型に合わせて、水、水溶性有機溶媒、油脂、ロウ、高級脂肪酸、高級アルコール、エステル類等の従来公知の化粧料基材が適宜選択される。
また、本発明の化粧料組成物には、本発明の効果を損なわない範囲で通常化粧料や皮膚外用医薬で使用される任意の成分を添加することができる。かかる任意成分の具体例としては、増粘・ゲル化剤、酸化防止剤、紫外線吸収剤、色素剤、金属封鎖剤、防腐剤、ｐＨ調整剤、香料、ミツロウ等が挙げられる。これら任意成分の配合割合は、その目的に応じて適宜選択して決定することができる。また、本発明の効果を損なわない範囲で、他の薬効植物抽出物を添加してもよい。
As a cosmetic base material when the hyaluronidase inhibitor of the present invention is used in a cosmetic composition, water, a water-soluble organic solvent, an oil or fat, a wax, a higher fatty acid, a higher alcohol, an ester is selected according to the intended dosage form. A conventionally known cosmetic base material such as the above is appropriately selected.
Moreover, in the cosmetic composition of this invention, the arbitrary components normally used by cosmetics and a skin external medicine can be added in the range which does not impair the effect of this invention. Specific examples of such optional components include thickening / gelling agents, antioxidants, ultraviolet absorbers, pigments, metal sequestering agents, preservatives, pH adjusters, fragrances, beeswax and the like. The blending ratio of these optional components can be selected and determined as appropriate according to the purpose. Moreover, you may add another medicinal plant extract in the range which does not impair the effect of this invention.
本発明の化粧料組成物を、入浴剤、ボディーソープ、シャンプー等の製品として用いる場合、剤型としては、一般に用いられる、水溶液、Ｗ／Ｏ型又はＯ／Ｗ型エマルション、適当な賦形剤等を用いて顆粒剤その他の粉末、錠剤等としてもよい。これらの形態にする際、さらに薬草や天然の精油など、化粧料組成物に使用できる公知のものを加えることができる。皮膚の保湿や美容のためになる適宜の成分、例えばヒアルロン酸や、コエンザイムＱ１０などをさらに加えてもよい。また、本発明の化粧料組成物は、ムースや育毛などのヘアケア剤として使用することもできる。 When the cosmetic composition of the present invention is used as a product such as a bath preparation, body soap, shampoo, etc., as a dosage form, generally used aqueous solution, W / O type or O / W type emulsion, suitable excipient Etc. may be used as granules, other powders, tablets and the like. In making these forms, known ones that can be used in cosmetic compositions such as herbs and natural essential oils can be added. Appropriate ingredients for moisturizing the skin and beauty, such as hyaluronic acid and coenzyme Q10 may be further added. Moreover, the cosmetic composition of the present invention can also be used as a hair care agent such as mousse or hair growth.
（機能性食品）
本発明のヒアルロニダーゼ阻害剤は、日常的に経口摂取しやいように、各種の食品、飲料と混ぜて機能性食品とすることで、長期的に摂取することも容易である。
ここでいう「機能性食品」とは、一般食品に加えて、健康の維持の目的で摂取する食品および／又は飲料を意味し、保健機能食品である特定保健用食品や栄養機能食品や、健康食品、栄養補助食品、栄養保険食品等を含む概念である。この中でも保健機能食品である特定保健用食品や栄養機能食品が好ましい機能性食品の態様である。なお、機能性食品として製品化する場合には、食品に用いられる様々な添加剤、具体的には、着色料、保存料、増粘安定剤、酸化防止剤、漂白剤、防菌防黴剤、酸味料、調味料、乳化剤、強化剤、製造用剤、香料等を添加していてもよい。
(Functional food)
The hyaluronidase inhibitor of the present invention can be easily ingested for a long period of time by mixing it with various foods and beverages so as to be taken orally on a daily basis to make a functional food.
The term “functional food” as used herein means foods and / or beverages ingested for the purpose of maintaining health, in addition to general foods. It is a concept that includes food, nutritional supplements, nutrition insurance foods, and the like. Among these, the food for specific health and the nutritional functional food which are health functional foods are preferable functional foods. In addition, when commercializing as a functional food, various additives used in food, specifically, coloring agents, preservatives, thickening stabilizers, antioxidants, bleaching agents, antibacterial and antifungal agents , Acidulants, seasonings, emulsifiers, reinforcing agents, production agents, fragrances and the like may be added.
本発明の機能性食品の対象となる、食品、飲料は特に限定されるものではない。例えば、食品として、ソーセージ、ハム、魚介加工品、ゼリー、キャンディー、チューインガムなどの食品類が挙げられる。また、飲料としては、各種の茶類、清涼飲料水、酒類、栄養ドリンクなどが挙げられる。また、例えばゼリーや寒天などを固める前に本発明の米麹加工物を含有した汁を混ぜたものなどでもよい。
本発明のヒアルロニダーゼ阻害剤は、このような食品、飲料に添加することにより、簡易に経口摂取することができる。
The foods and beverages that are the targets of the functional food of the present invention are not particularly limited. Examples of food include foods such as sausage, ham, processed seafood, jelly, candy, and chewing gum. Examples of the beverage include various teas, soft drinks, alcoholic beverages, and energy drinks. Further, for example, a mixture of juice containing the processed rice bran of the present invention before hardening jelly or agar may be used.
The hyaluronidase inhibitor of the present invention can be easily taken orally by adding to such foods and beverages.
機能性食品への本発明の阻害剤の配合割合は任意であり、機能性食品の種類に応じて適宜選択できる。 The mixing ratio of the inhibitor of the present invention to the functional food is arbitrary, and can be appropriately selected according to the type of the functional food.
本発明のヒアルロニダーゼ阻害剤は、ヒト以外の動物に対して適用することもできる。そのため、ペットフード等の動物用機能性食品へ添加することもできる。 The hyaluronidase inhibitor of the present invention can also be applied to animals other than humans. Therefore, it can also be added to animal functional foods such as pet food.
以下に実施例を挙げて本発明をより具体的に説明する。なお、上述のように本発明の米麹加工物としては、粉末など適宜の形態を選択することができ、本発明に係る米麹加工物は、以下のような水溶媒抽出物の実施例に限定されない。 Hereinafter, the present invention will be described more specifically with reference to examples. As described above, as the rice bran processed product of the present invention, an appropriate form such as powder can be selected. It is not limited.
１．使用した米麹
＜米麹（白麹菌）＞
白麹菌(Aspergillus kawachii)を繁殖させた米麹は、株式会社ビオックから入手した白麹Ｋ型菌を用いて製造した。
＜米麹（黒麹菌）＞
黒麹菌（Aspergillus awamori）を繁殖させた米麹は、株式会社ビオックから入手した泡盛用黒麹種菌を用いて製造した。
＜米麹（黄麹菌）＞
黄麹菌（Aspergillus oryzae）を繁殖させた米麹は、株式会社ビオックから入手した清酒用黄麹種菌を用いて製造した。
1. Used rice bran <rice bran (white bacterium)>
A rice bran with which white birch (Aspergillus kawachii) was propagated was produced using white birch K-type fungus obtained from Bioc Co., Ltd.
<Rice bran (Koji mold)>
The rice bran with which Aspergillus awamori was propagated was produced using the black potato inoculum for awamori obtained from Bioc Co., Ltd.
<Rice bran (yellow gonococcus)>
A rice bran having been bred with Aspergillus oryzae was produced using a koji inoculum for sake obtained from Bioc Co., Ltd.
２．米麹の水抽出物の調製
抽出溶媒としての水（５０ｍＬ）に、米麹（白麹菌）（５ｇ）を浸漬し、室温で３時間静置した。遠心分離後、上澄みを濾過して白麹水抽出物を得、後述のヒアルロニダーゼ阻害活性の評価に供した。
米麹（白麹菌）に代えて、米麹（黒麹菌）を使用した以外は、上記白麹水抽出物の調製と同様にして黒麹水抽出物を得、後述のヒアルロニダーゼ阻害活性の評価に供した。
米麹（白麹菌）に代えて、米麹（黄麹菌）を使用した以外は、上記白麹水抽出物の調製と同様にして黄麹水抽出物を得、後述のヒアルロニダーゼ阻害活性の評価に供した。
2. Preparation of water extract of rice bran Rice bran (white mold) (5 g) was immersed in water (50 mL) as an extraction solvent and allowed to stand at room temperature for 3 hours. After centrifugation, the supernatant was filtered to obtain a birch water extract, which was subjected to evaluation of hyaluronidase inhibitory activity described later.
Except for using rice bran (black koji mold) instead of rice koji (white koji mold), a black koji water extract was obtained in the same manner as the above white koji water extract preparation, and the hyaluronidase inhibitory activity described below was evaluated. Provided.
Except for using rice bran (yellow koji) instead of rice koji (white koji), a yellow koji water extract was obtained in the same manner as the above white koji water extract, and the hyaluronidase inhibitory activity described below was evaluated. Provided.
３．ヒアルロニダーゼ活性阻害率の評価方法
０．１Ｍの酢酸緩衝液（ｐＨ４．０）で４ｍｇ／ｍＬの濃度になるように調製したウシ精巣由来ヒアルロニダーゼ（ＳＩＧＭＡ−ＡＬＤＲＩＣＨ社製）溶液５０μＬを、米麹の抽出物１００μＬに添加し、撹拌後、３７℃で２０分間インキュベートした。
次に、ヒアルロニダーゼ溶液に米麹の抽出物を添加したこの溶液に、同緩衝液で０.５ｍｇ／ｍＬの濃度になるように調製したＣｏｍｐｏｕｎｄ４８／８０溶液を１００μＬ添加し、３７℃で２０分間インキュベートし、ヒアルロニダーゼを活性化させた。
さらに、ヒアルロニダーゼを活性化させたこの溶液に、同緩衝液で０．８ｍｇ／ｍＬの濃度になるように調製した鶏冠由来ヒアルロン酸（和光純薬社製）溶液を２５０μＬ添加し、３７℃で４０分間反応させた。
この酵素反応をさせた反応液に、０．４ＮのＮａＯＨ溶液を１００μＬ添加し、反応を停止させた。次に、０．８Ｍのホウ酸溶液（ｐＨ９．１）を１００μＬ添加し、９５℃で３分間加温した後、水冷した。水冷したこの溶液に対して１％p-ジメチルアミノベンズアルデヒド試薬を３ｍＬ添加し、３７℃で２０分間反応後、５８５ｎｍにおける吸光度を測定した（Ａ）。さらに酵素を添加せずに緩衝液を加えて同様の操作と測定を行った（Ｂ）。（Ａ），（Ｂ）と同様の操作と測定を、試料を添加せずに水を加えてそれぞれ実施した（Ｃ、Ｄ）。上記方法で吸光度を求め、次式により、阻害率を算出した。
ヒアルロニダーゼ活性阻害率（％）＝[１−（Ａ−Ｂ）/（Ｃ−Ｄ）] × １００
3. Evaluation Method of Hyaluronidase Activity Inhibition Rate Extraction of rice bran with 50 μL of bovine testis-derived hyaluronidase (manufactured by SIGMA-ALDRICH) prepared to a concentration of 4 mg / mL with 0.1 M acetate buffer (pH 4.0) After stirring, the mixture was incubated at 37 ° C. for 20 minutes.
Next, 100 μL of Compound 48/80 solution prepared to the concentration of 0.5 mg / mL with the same buffer solution was added to this solution obtained by adding rice bran extract to hyaluronidase solution, and incubated at 37 ° C. for 20 minutes. Then, hyaluronidase was activated.
Furthermore, 250 μL of a chicken crown-derived hyaluronic acid solution (manufactured by Wako Pure Chemical Industries, Ltd.) prepared to the concentration of 0.8 mg / mL with the same buffer solution was added to this solution in which hyaluronidase had been activated, Reacted for 1 minute.
100 μL of 0.4N NaOH solution was added to the reaction solution subjected to the enzyme reaction to stop the reaction. Next, 100 μL of 0.8 M boric acid solution (pH 9.1) was added, and the mixture was heated at 95 ° C. for 3 minutes, and then cooled with water. To this water-cooled solution, 3 mL of 1% p-dimethylaminobenzaldehyde reagent was added, reacted at 37 ° C. for 20 minutes, and the absorbance at 585 nm was measured (A). Further, a buffer solution was added without adding the enzyme, and the same operation and measurement were performed (B). The same operations and measurements as in (A) and (B) were performed by adding water without adding a sample (C, D). Absorbance was calculated | required with the said method, and the inhibition rate was computed by following Formula.
Hyaluronidase activity inhibition rate (%) = [1− (A−B) / (C−D)] × 100
評価１：米麹の種類とヒアルロニダーゼ阻害作用の関係
白麹水抽出物、黒麹水抽出物及び黄麹水抽出物について、上述の方法でヒアルロニダーゼの阻害率を評価した。結果を図１に示す。
Evaluation 1: Relationship between Kind of Rice Bran and Hyaluronidase Inhibitory Action The inhibition rate of hyaluronidase was evaluated by the above-described method for the white birch water extract, the black birch water extract and the yellow jade water extract. The results are shown in FIG.
図１に示されるように、白麹水抽出物、黒麹水抽出物及び黄麹水抽出物のいずれもがヒアルロニダーゼ阻害活性を有していた。 As shown in FIG. 1, all of the white glaze water extract, black glaze water extract, and jaundice water extract had hyaluronidase inhibitory activity.
本発明のヒアルロニダーゼ阻害剤は、優れたヒアルロニダーゼ活性阻害作用を示すため、各種化粧料組成物、機能性食品等の用途に使用することができる。 Since the hyaluronidase inhibitor of the present invention exhibits an excellent hyaluronidase activity inhibitory action, it can be used for various cosmetic compositions, functional foods and the like.
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| JP2015140325A (en) * | 2014-01-30 | 2015-08-03 | 福岡県 | Collagenase inhibitor, and cosmetic composition and functional food which contain collagenase inhibitor |
| JP2017122122A (en) * | 2015-10-08 | 2017-07-13 | 福岡県 | Hyaluronidase inhibitor, and cosmetic composition and functional food comprising the same |
| EP3967370A4 (en) * | 2019-05-10 | 2022-07-20 | Kohsei Industrial Co., Ltd. | Gene expression promoter for beautiful skin |
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| JPS6168404A (en) * | 1984-09-13 | 1986-04-08 | Tokuyama Toshie | Production of cosmetic from rice |
| JPS6187615A (en) * | 1984-10-08 | 1986-05-06 | Tokuyama Toshie | Preparation of cosmetic from rice |
| JP3367709B2 (en) * | 1993-06-18 | 2003-01-20 | 株式会社創研 | Cosmetics from rice |
| JP3116160B2 (en) * | 1997-09-25 | 2000-12-11 | 千枝子 椛島 | Method for producing basic cosmetic for skin conditioning |
| JP4871438B2 (en) * | 1999-09-22 | 2012-02-08 | 帝國製薬株式会社 | Cosmetics |
| JP2001089355A (en) * | 1999-09-22 | 2001-04-03 | Tokushima Seiko Kk | Cosmetic component comprising rice koji, dried koji and dried powdery koji, and its preparation method |
| JP5414137B2 (en) * | 2001-03-30 | 2014-02-12 | 三省製薬株式会社 | Hyaluronidase activity inhibitor |
| JP4484014B2 (en) * | 2002-03-07 | 2010-06-16 | ヒガシマル醤油株式会社 | Hyaluronidase inhibition, antiallergic activity and immunostimulatory substances |
| JP2006062984A (en) * | 2004-08-25 | 2006-03-09 | Yukihiro Hirose | Antiaging composition, cosmetic containing the same, and food and drink containing the same |
| JP2006069948A (en) * | 2004-09-01 | 2006-03-16 | Yukihiro Hirose | Anti-aging composition and cosmetics, beverages and foods containing the same |
| JP5090014B2 (en) * | 2007-01-26 | 2012-12-05 | 洋佑 清水 | Fermented composition and food, beverage and pharmaceutical product using the composition |
| JP2012012367A (en) * | 2010-07-05 | 2012-01-19 | Toyo Shinyaku Co Ltd | Hyaluronidase activity inhibitor |
| JP6544503B2 (en) * | 2014-01-30 | 2019-07-17 | 福岡県 | Cosmetic composition and functional food containing collagenase inhibitor and collagenase inhibitor |
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| JP2015140325A (en) * | 2014-01-30 | 2015-08-03 | 福岡県 | Collagenase inhibitor, and cosmetic composition and functional food which contain collagenase inhibitor |
| JP2017122122A (en) * | 2015-10-08 | 2017-07-13 | 福岡県 | Hyaluronidase inhibitor, and cosmetic composition and functional food comprising the same |
| JP7292568B2 (en) | 2015-10-08 | 2023-06-19 | 福岡県 | Hyaluronidase inhibitor, and cosmetic composition and functional food containing same |
| EP3967370A4 (en) * | 2019-05-10 | 2022-07-20 | Kohsei Industrial Co., Ltd. | Gene expression promoter for beautiful skin |
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