JP3242997B2 - Hyaluronidase activity inhibitor - Google Patents
Hyaluronidase activity inhibitorInfo
- Publication number
- JP3242997B2 JP3242997B2 JP19020392A JP19020392A JP3242997B2 JP 3242997 B2 JP3242997 B2 JP 3242997B2 JP 19020392 A JP19020392 A JP 19020392A JP 19020392 A JP19020392 A JP 19020392A JP 3242997 B2 JP3242997 B2 JP 3242997B2
- Authority
- JP
- Japan
- Prior art keywords
- hyaluronidase activity
- activity inhibitor
- hyaluronidase
- present
- theaflavin
- 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.)
- Expired - Fee Related
Links
Landscapes
- Pyrane Compounds (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、ヒアルロニダーゼ活性
阻害剤に関し、詳しくはヒアルロニダーゼに特異的に作
用して、その活性化を阻害するテアフラビン類を有効成
分として含むヒアルロニダーゼ活性阻害剤に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hyaluronidase activity inhibitor, and more particularly to a hyaluronidase activity inhibitor containing , as an active ingredient, theaflavins which specifically act on hyaluronidase and inhibit its activation.
【０００２】[0002]
【従来の技術および発明が解決しようとする課題】ヒア
ルロニダーゼは動物の睾丸や蛇毒、細菌等に存在する酵
素であり、動物の結合組織に広く分布しているヒアルロ
ン酸の加水分解酵素である。ヒアルロニダーゼは起炎症
剤としての作用を持つことが知られている。一方、抗炎
症剤や抗アレルギー剤により活性が阻害されることか
ら、ヒアルロニダーゼ活性を阻害することにより、炎症
やアレルギーを軽減することが可能であると考えられて
いる。さらには、クリーム，乳液，口紅，ヘアー製品な
どの化粧品に混合されたヒアルロン酸の分解を防ぐこと
も期待される。そこで、本発明者らはヒアルロニダーゼ
の活性化を阻害し、かつ人体に対して有害な副作用を有
さない酵素阻害剤の開発を試みた。2. Description of the Related Art Hyaluronidase is an enzyme present in animal testes, snake venom, bacteria and the like, and is a hyaluronic acid hydrolase widely distributed in connective tissues of animals. Hyaluronidase is known to have an action as an anti-inflammatory agent. On the other hand, since the activity is inhibited by an anti-inflammatory agent or an anti-allergic agent, it is considered that inflammation and allergy can be reduced by inhibiting hyaluronidase activity. Furthermore, it is expected to prevent degradation of hyaluronic acid mixed in cosmetics such as creams, emulsions, lipsticks, and hair products. Thus, the present inventors have attempted to develop an enzyme inhibitor that inhibits the activation of hyaluronidase and has no harmful side effects on the human body.
【０００３】[0003]
【課題を解決するための手段】本発明者らは化学合成品
でなく、天然物の中から目的とする薬効を有する物質を
検索すべく鋭意研究を重ねた結果、テアフラビン類に該
物質が含まれていることを見出し、本発明に到達した。
すなわち、本発明はテアフラビンモノガレートＡ，テア
フラビンモノガレート Ｂ及びテアフラビンジガレートの
中から選ばれた少なくとも１種の物質を有効成分として
含むヒアルロニダーゼ活性阻害剤を提供するものであ
る。本発明のヒアルロニダーゼ活性阻害剤の主成分であ
るテアフラビン類は、下記の一般式Ｉで表される。Means for Solving the Problems The present inventors have conducted intensive studies to search for a substance having a desired medicinal effect from natural products, not from chemically synthesized products. As a result, the theaflavins contained the substance. The inventors have found that the present invention has been performed, and arrived at the present invention.
That is, the present invention relates to theaflavin monogallate A,
Flavin monogallate B and theaflavin digallate
It is intended to provide a hyaluronidase activity inhibitor comprising at least one substance selected from the group as an active ingredient. Theaflavins, which are the main components of the hyaluronidase activity inhibitor of the present invention , are represented by the following general formula I.
【０００４】[0004]
【化１】 Embedded image
【０００５】（式中、Ｒ3及びＲ4はＨまたは(Wherein R 3 and R 4 are H or
【０００６】[0006]
【化２】 Embedded image
【０００７】を示し、Ｒ3及びＲ4は同じであっても異な
っていてもよい。）Wherein R 3 and R 4 may be the same or different. )
【０００８】次に、上記の一般式Ｉで表されるテアフラ
ビン類を具体的に示すと、以下のものがある。テアフラ
ビンモノガレートＡ（一般式Ｉ中、Ｒ3＝Next, the theafla represented by the above general formula I
Specific examples of the bottles include the following. Theafra
Bin monogallate A (in the general formula I , R 3 =
【０００９】[0009]
【化３】 Embedded image
【００１０】，Ｒ4＝Ｈのもの） テアフラビンモノガレートＢ（一般式Ｉ中、Ｒ3＝Ｈ，
Ｒ4＝[0010] those of R 4 = H) theaflavin monogallate B (In the formula I, R 3 = H,
R 4 =
【００１１】[0011]
【化４】 Embedded image
【００１２】のもの） テアフラビンジガレート（一般式Ｉ中、Ｒ3，Ｒ4＝[0012] one) theaflavin digallate (in the general formula I, R 3, R 4 =
【００１３】[0013]
【化５】 Embedded image
【００１４】のもの） 上記テアフラビン類は茶葉を原料として製造することが
でき、その製法は特開昭５９−２１９３８４号公報，同
６０−１３７８０号公報，同６１−１３０２８５号公報
などに記載されている。The theaflavins can be produced using tea leaves as a raw material, and their production methods are described in JP-A-59-219384, JP-A-60-13780, JP-A-61-130285 and the like. I have.
【００１５】本発明のヒアルロニダーゼ活性阻害剤は、
単独で使用する他、適当な賦形剤、例えばゼラチン，ア
ルギン酸ナトリウムなどと混合したり、水，アルコール
類などの溶媒、カルボキシメチルセルロースなどの希釈
剤等と組合わせて用いられる。本発明のヒアルロニダー
ゼ活性阻害剤の使用量については、薬剤として人体に投
与する場合、通常は１日量が0.５〜１０ｇ、好ましくは
１〜３ｇ程度となるように経口的に服用すればよい。剤
形は任意で散剤，錠剤，カプセル剤などとして用いる。
また、化粧品などに配合する場合は、最終濃度が１〜１
００ppm となるように添加すればよい。The hyaluronidase activity inhibitor of the present invention comprises:
In addition to being used alone, it is used by mixing with an appropriate excipient, for example, gelatin, sodium alginate or the like, or in combination with a solvent such as water or alcohols, or a diluent such as carboxymethyl cellulose. Regarding the use amount of the hyaluronidase activity inhibitor of the present invention, when administered to the human body as a drug, it may be taken orally so that the daily dose is usually 0.5 to 10 g, preferably about 1 to 3 g. . The dosage form is optionally used as a powder, tablet, capsule or the like.
When blended in cosmetics, etc., the final concentration is 1-1.
What is necessary is just to add so that it may become 00 ppm.
【００１６】[0016]
【実施例】次に、本発明を実施例により詳しく説明す
る。なお、阻害能の測定は常法に基づき次の方法で行っ
た。ヒアルロニダーゼ活性阻害剤溶液（1 mM) ５０μl
に酵素（from Bovine testis, SIGMA 社製）溶液100 μ
l (2,000 unit/ml緩衝液）を加え、３７℃で２０分間放
置する。 次に、酵素活性化剤（商品名：compound 48/8
0、SIGMA 社製）溶液（0.1mg/ml緩衝液）１００μl を
加え、 ３７℃で２０分間放置した後、 基質であるヒアル
ロン酸（from rooster comb, WAKO 社製）溶液（0.8 mg
/ml 緩衝液）２５０μl を入れ３７℃で４０分間放置し
た。 0.4N NaOH １００μl を加えて反応を停止させた
後、 Morgan-Elson法の変法（Davidson,E. A.,Aronson,
N. N.: J.Biol. Chem. 242, 437(1967)) により生成物
の定量を行い、ヒアルロニダーゼ活性阻害能を求めた。
阻害活性は次の式から求められる阻害率で表した。 ま
た、緩衝液には0.1 M 酢酸緩衝液（pH 4.0）を用いた。Next, the present invention will be described in detail with reference to examples. In addition, the measurement of the inhibitory ability was performed by the following method based on a conventional method. Hyaluronidase activity inhibitor solution (1 mM) 50 μl
And an enzyme (from Bovine testis, SIGMA) solution 100 μl
l (2,000 unit / ml buffer) and leave at 37 ° C for 20 minutes. Next, an enzyme activator (trade name: compound 48/8)
0, SIGMA) solution (0.1 mg / ml buffer) (100 µl) and left at 37 ° C for 20 minutes.
/ ml buffer) and left at 37 ° C for 40 minutes. After stopping the reaction by adding 100 μl of 0.4N NaOH, a modification of the Morgan-Elson method (Davidson, EA, Aronson,
NN: J. Biol. Chem. 242, 437 (1967)), the product was quantified, and the ability to inhibit hyaluronidase activity was determined.
The inhibitory activity was represented by the inhibition rate determined from the following equation. The buffer used was 0.1 M acetate buffer (pH 4.0).
【００１７】[0017]
【数１】阻害率(%)=[(A-B)-(C-D)]/(A-B)×100## EQU1 ## Inhibition rate (%) = [(A-B)-(C-D)] / (A-B) × 100
【００１８】 A:対照溶液の５８５nmにおける吸光度 B:対照溶液blank の５８５nmにおける吸光度 C:阻害剤溶液の５８５nmにおける吸光度 D:阻害剤溶液blank の５８５nmにおける吸光度A: absorbance of control solution at 585 nm B: absorbance of control solution blank at 585 nm C: absorbance of inhibitor solution at 585 nm D: absorbance of inhibitor solution blank at 585 nm
【００１９】実施例１及び比較例１ ヒアルロニダーゼ活性阻害剤として第１表に示した各種
茶ポリフェノール類を使用し、上記した方法で各物質の
ヒアルロニダーゼ活性阻害能を求めた。結果を第１表に
示す。 Example 1 and Comparative Example 1 Using the various tea polyphenols shown in Table 1 as hyaluronidase activity inhibitors, the ability of each substance to inhibit the hyaluronidase activity was determined by the method described above. The results are shown in Table 1.
【００２０】[0020]
【表１】第 １ 表 [Table 1] Table 1
【００２１】表から明らかなように、テアフラビンモノ
ガレートＡ，テアフラビンモノガレートＢ，テアフラビ
ンジガレートが強いヒアルロニダーゼ活性阻害能を持つ
ことが確認された。As is clear from the table, theaflavin mono
It was confirmed that gallate A , theaflavin monogallate B, and theaflavin digallate have strong hyaluronidase activity inhibiting ability.
【００２２】[0022]
【発明の効果】本発明のヒアルロニダーゼ活性阻害剤
は、日常相当量飲用されている茶から抽出される天然物
を主成分とするため、薬剤としても人体に対する副作用
の心配がない。しかも、本発明のヒアルロニダーゼ活性
阻害剤は低濃度の添加でヒアルロニダーゼの活性化を著
しく阻害する。したがって、本発明のヒアルロニダーゼ
活性阻害剤は医薬として各種炎症やアレルギーを軽減す
るために用いる他、化粧品等に添加してヒアルロン酸の
分解を防ぐことができる。Industrial Applicability The hyaluronidase activity inhibitor of the present invention contains, as a main component, a natural product extracted from tea which is consumed in a considerable amount every day, so that there is no concern about side effects on the human body as a drug. Moreover, the hyaluronidase activity inhibitor of the present invention significantly inhibits the activation of hyaluronidase when added at a low concentration. Therefore, the hyaluronidase activity inhibitor of the present invention can be used as a medicine for reducing various inflammations and allergies, and can be added to cosmetics and the like to prevent the degradation of hyaluronic acid.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ Ａ６１Ｐ 37/08 Ａ６１Ｐ 37/08 43/00 １１１ 43/00 １１１ Ｃ０７Ｄ 311/62 Ｃ０７Ｄ 311/62 (58)調査した分野(Int.Cl.7，ＤＢ名) C07D 311/00 - 311/96 ＣＡ（ＳＴＮ) ＲＥＧＩＳＴＲＹ（ＳＴＮ)────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. 7 Identification code FI A61P 37/08 A61P 37/08 43/00 111 43/00 111 C07D 311/62 C07D 311/62 (58) Fields surveyed (Int. .Cl. 7 , DB name) C07D 311/00-311/96 CA (STN) REGISTRY (STN)
Claims (1)
ビンモノガレートＢ及びテアフラビンジガレートの中か
ら選ばれた少なくとも１種の物質を有効成分として含む
ヒアルロニダーゼ活性阻害剤。1. Theaflavin monogallate A, theaflavin
In bin monogallate B and theaflavin digallate
A hyaluronidase activity inhibitor comprising, as an active ingredient, at least one substance selected from the group consisting of:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19020392A JP3242997B2 (en) | 1992-06-25 | 1992-06-25 | Hyaluronidase activity inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19020392A JP3242997B2 (en) | 1992-06-25 | 1992-06-25 | Hyaluronidase activity inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH069391A JPH069391A (en) | 1994-01-18 |
| JP3242997B2 true JP3242997B2 (en) | 2001-12-25 |
Family
ID=16254179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP19020392A Expired - Fee Related JP3242997B2 (en) | 1992-06-25 | 1992-06-25 | Hyaluronidase activity inhibitor |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3242997B2 (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06172122A (en) * | 1992-08-31 | 1994-06-21 | Uenoya Honpo:Kk | Production of cosmetic |
| US5674477A (en) * | 1995-02-28 | 1997-10-07 | Ahluwalia; Gurpreet S. | Reduction of hair growth |
| JPH0987189A (en) * | 1995-09-19 | 1997-03-31 | Ichimaru Pharcos Co Ltd | Antiallergic agent containing isodon japonicus hara, paeonia suffruticosa andrews, perilla frutescens britton var. acuta kudo, and/or arunica montana linne |
| JP2000319159A (en) * | 1999-05-10 | 2000-11-21 | Nonogawa Shoji Kk | Skin preparation for external use |
| EP1157693A1 (en) * | 2000-05-12 | 2001-11-28 | National Agricultural Research Organisation (NARO) | Use of epigallocatechin 3-o-(3-o-methyl) gallate and/or epigallocatechin 3-o-(4-o-methyl) gallate for the treatment of allergy and/or inflammation |
| WO2002039956A2 (en) | 2000-11-15 | 2002-05-23 | Rutgers, The State University Of New Jersey | Black tea extract for prevention of disease |
| JP4781580B2 (en) * | 2001-09-26 | 2011-09-28 | 日本メナード化粧品株式会社 | Collagenase inhibitor |
| WO2006124033A2 (en) * | 2005-05-17 | 2006-11-23 | Mitsui Norin Co., Ltd | Compositions and methods for reduction of cutaneous photoageing |
| JP4456585B2 (en) | 2006-09-06 | 2010-04-28 | 株式会社ノエビア | Cell activator, collagen production promoter, whitening agent, antioxidant, anti-inflammatory agent, aromatase activity promoter, protease activity promoter, topical skin preparation and food |
| JP2012072084A (en) * | 2010-09-29 | 2012-04-12 | Kracie Home Products Ltd | Elastase inhibitor, and cosmetic composition and pharmaceutical composition comprising the same |
| CN108721193A (en) * | 2017-04-17 | 2018-11-02 | 哈尔滨工业大学（威海） | A kind of edible health care lipstick |
-
1992
- 1992-06-25 JP JP19020392A patent/JP3242997B2/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| 食品衛生学雑誌，Ｖｏｌ．３１，Ｎｏ．３，ｐｐ．２３３−２３７ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH069391A (en) | 1994-01-18 |
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