JP6386053B2 - Hair growth or hair growth promoting composition containing 21-O-angeloyl theasapogenol E3 - Google Patents
Hair growth or hair growth promoting composition containing 21-O-angeloyl theasapogenol E3 Download PDFInfo
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- JP6386053B2 JP6386053B2 JP2016538842A JP2016538842A JP6386053B2 JP 6386053 B2 JP6386053 B2 JP 6386053B2 JP 2016538842 A JP2016538842 A JP 2016538842A JP 2016538842 A JP2016538842 A JP 2016538842A JP 6386053 B2 JP6386053 B2 JP 6386053B2
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/63—Steroids; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
Landscapes
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- Organic Chemistry (AREA)
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- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は、一側面において、発毛または育毛促進用組成物に関し、他の一側面において、21‐O‐アンゲロイルテアサポゲノール(21‐O‐angeloyltheasapogenol)E3を含み、毛髪の周期のうち休止期から成長期へ移行する周期を短縮させて毛髪の成長を促進させる発毛または育毛促進用組成物に関する。 In one aspect, the present invention relates to a composition for promoting hair growth or hair growth, and in another aspect, includes 21-O-angeloylteaasapogenol E3, The present invention relates to a composition for promoting hair growth or hair growth, which accelerates hair growth by shortening the period of transition from the rest period to the growth period.
脱毛の原因としては、男性ホルモン作用過剰説、皮脂分泌過剰説、血液循環不良説、過酸化物、細菌等による頭皮機能低下説、遺伝的要因、老化、ストレス等が議論されている。これに加え、社会的ストレスの増加とともに、環境汚染およびインスタント食品等の西欧化された食習慣、頻繁なパーマや染色等により脱毛人口が次第に増加している。毛髪の周期は、毛髪を成長させる成長期(anagen)、成長を終了し、毛球部が縮小する時期である退行期(catagen)、毛乳頭が活動を停止し、毛髪を頭皮に留まらせる時期である休止期(talogen)、毛乳頭が活動を開始し、または新たな毛髪を発生させて、古い毛髪を脱毛させる時期である発生期に分けることができる。 The causes of hair loss have been discussed, such as male hormone overactivity theory, excessive sebum secretion theory, poor blood circulation theory, hypoxia, hypothesis of scalp function due to bacteria, genetic factors, aging, stress, and the like. In addition to this, along with the increase in social stress, the hair loss population is gradually increasing due to environmental pollution and westernized eating habits such as instant foods, frequent perms and dyeing. The period of the hair is the growth period (anagen) in which the hair grows, the regression period (catagen) in which the growth ends and the hair bulb shrinks, and the time in which the hair papilla stops its activity and the hair stays on the scalp Can be divided into the genus, which is the time when the dermal papilla begins to act, or when new hair is generated and the old hair is removed.
成長期(Anagen Stage;2〜7年)は、毛髪が成長する期間で、再び毛髪が毛球から毛包に出ようとする毛髪生成段階と、硬いケラチンが毛嚢の中で作られる段階とに分けられる。毛髪は、退行期まで自己成長を続ける。退行期(Catagen Stage;2〜3週間)は、成長期が終わり、毛髪の形態を維持しつつ代謝過程が遅くなる時期で、この段階では、ケラチンを作り出さない。退行期は、毛髪全体の1%を占める。このとき、毛球部が収縮して毛乳頭から分かれ、毛嚢に覆われて上方に上がっていき、細胞分裂は停止状態となる。休止期(Talogen Stage;3ヶ月)は、毛乳頭が萎縮し、毛嚢が徐々に萎びていき、毛根が上方に押し上げられて抜ける。毛髪がなくなる時期であり、次の成長期段階が始まるまでの寿命は、3〜4ヶ月である。 Growth stage (Anagen Stage; 2 to 7 years) is a period in which hair grows, in which hair is about to come out of the hair bulb into the hair follicle, and in which hard keratin is made in the hair follicle. It is divided into. The hair continues to grow until the regression phase. The regression phase (Catagen Stage; 2-3 weeks) is the period when the growth phase ends and the metabolic process slows down while maintaining the shape of the hair. At this stage, no keratin is produced. The regression phase accounts for 1% of the total hair. At this time, the hair bulb part contracts and separates from the hair papilla, is covered with the hair follicle and moves upward, and cell division is stopped. In the resting period (Talogen Stage; 3 months), the hair papilla shrinks, the hair follicle gradually shrinks, and the hair root is pushed upward and comes off. This is the time when the hair disappears, and the lifetime until the next growth phase begins is 3-4 months.
正常な人の場合、成長期状態の毛髪が多いのに比べ、脱毛症(Alopecia)の人は、休止期状態の毛髪が多く、目に見える脱毛現象が現れるようになる。脱毛が進行するほど成長期の期間が短くなり、これにより、毛髪はますます小型化する。したがって、脱毛の治療のためには、休止期状態の毛嚢を、成長期に速やかに進むことができようにし、短くなった成長期を増やしてやることが重要である。 A normal person has more hair in the growth phase, and a person with alopecia (Alopecia) has more hair in the resting state, and a visible hair loss phenomenon appears. As hair removal progresses, the period of the growth phase is shortened, which makes the hair increasingly smaller. Therefore, for the treatment of hair loss, it is important to allow the hair follicles in the resting state to proceed promptly to the growth phase and increase the shortened growth phase.
男性型脱毛症は、テストステロン(Testosterone)という男性ホルモンによって現れる現象で、このテストステロンが、5α‐リダクターゼ(α‐reductase)という酵素によって、より強力なホルモンであるジヒドロテストステロン(Dihydrotestosterone,DHT)に変わると、このホルモンが毛嚢に作用して毛嚢を成長期段階から退行期段階へと誘導して、脱毛を引き起こさせる。したがって、男性型脱毛症を治療するために、5α‐リダクターゼによるDHTの生成を抑制する方法が主に使用される。 Male pattern alopecia is a phenomenon manifested by a male hormone called Testosterone. When this testosterone is changed to dihydrotestosterone (DHT), which is a more powerful hormone, by an enzyme called 5α-reductase. This hormone acts on the hair follicle and induces the hair follicle from the growth phase to the regression phase, causing hair loss. Therefore, methods for inhibiting DHT production by 5α-reductase are mainly used to treat androgenetic alopecia.
女性型脱毛症は、主に閉経後のエストロゲン量の減少によって発生する。女性型脱毛症のための治療剤としては、主にミノキシジルやエストロゲンが使用されている。 Female pattern alopecia occurs mainly due to a decrease in postmenopausal estrogen levels. Minoxidil and estrogen are mainly used as therapeutic agents for female pattern alopecia.
円形脱毛症は、自己免疫疾患や精神的ストレス、遺伝的素因によって発生する。こうした円形脱毛症は、アンドロゲン性脱毛症とは根本的に原因が異なり、治療法もまた異なるため、副腎皮質ホルモン剤を処理する方法を使用したり、ミノキシジルを患部に塗ったり、人為的に患部に刺激を誘発したりする方法を使用する。 Alopecia areata is caused by autoimmune diseases, mental stress, and genetic predisposition. These alopecia areata are fundamentally different from androgenetic alopecia, and the treatment methods are also different, so it is possible to use a method of treating corticosteroids, apply minoxidil to the affected area, artificially affect the affected area Use methods to induce stimulation.
しかし、これまで、脱毛を防止し、発毛促進および毛髪の生長に効果を持っていると知られているミノキシジル(minoxidil)やトリコサッカライド(trichosaccharide)等の製剤の場合、はっきりとした効能の不在および人体安定性、皮膚刺激誘発等の副作用の問題が台頭していることから、安全性および効能が確保された組成物の開発が急がれている実情である。 However, in the case of preparations such as minoxidil and trichosaccharide, which have been known to be effective in preventing hair loss and promoting hair growth and hair growth, there is no clear lack of efficacy. In addition, since problems of side effects such as stability of human body and induction of skin irritation are emerging, development of a composition that ensures safety and efficacy is urgent.
前記のような問題点を解決するために、本発明は、一側面において、21‐O‐アンゲロイルテアサポゲノールE3が、これまで知られていなかった発毛または育毛促進効果があることを発見し、これを利用した化粧料組成物、薬学組成物および健康食品組成物を提供することをその目的とする。 In order to solve the above problems, the present invention is characterized in that, in one aspect, 21-O-angeloylteasapogenol E3 has a hair growth or hair growth promoting effect that has not been known so far. It is an object of the present invention to provide a cosmetic composition, a pharmaceutical composition and a health food composition that are discovered and utilized.
本発明は、一側面において、下記化学式1で表されるテアサポゲノール(theasapogenol)誘導体を有効成分として含有する、発毛または育毛促進用組成物を提供する。 In one aspect, the present invention provides a composition for promoting hair growth or hair growth, which contains a theasapogenol derivative represented by the following chemical formula 1 as an active ingredient.
前記式において、R1およびR2は、それぞれ独立して‐H、C1‐6アルキル、‐OH、‐R6OHまたは‐CHOであり、
R3は、‐H、C1‐6アルキル、‐OHまたは‐OOCR7であり、
R4は、‐Hまたは‐COR8であり、
R5は、‐HまたはC1‐6アルキルであり、
ここで、R6は、C1‐6アルキル、R7は、C2‐6アルケニル、およびR8は、C1‐6アルキルである。
In the above formula, R 1 and R 2 are each independently —H, C 1-6 alkyl, —OH, —R 6 OH or —CHO,
R 3 is —H, C 1-6 alkyl, —OH or —OOCR 7 ;
R 4 is —H or —COR 8 ;
R 5 is —H or C 1-6 alkyl;
Here, R 6 is C 1-6 alkyl, R 7 is C 2-6 alkenyl, and R 8 is C 1-6 alkyl.
本発明は、他の一側面において、21‐O‐アンゲロイルテアサポゲノール(21‐O‐angeloyltheasapogenol)E3を有効成分として含む、発毛または育毛促進用組成物を提供する。 In another aspect, the present invention provides a composition for promoting hair growth or hair growth comprising 21-O-angeloyltheasapogenol E3 as an active ingredient.
本発明は、また他の一側面において、緑茶サポニンから由来したテアサポゲノール誘導体を有効成分とし、かつ、一側面において、有効成分を組成物総重量を基準として0.001〜20重量%含有する、発毛または育毛促進用組成物を提供する。 According to another aspect of the present invention, a theasapogenol derivative derived from green tea saponin is used as an active ingredient, and in one aspect, the active ingredient is contained in an amount of 0.001 to 20% by weight based on the total weight of the composition. A composition for promoting hair or hair growth is provided.
本発明は、また他の一側面において、化粧料組成物、薬学組成物または食品組成物である、発毛または育毛促進用組成物を提供する。 In another aspect, the present invention provides a composition for promoting hair growth or hair growth, which is a cosmetic composition, pharmaceutical composition or food composition.
一側面において、本発明の組成物は、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3を含有することにより、従来の育毛剤よりも優れた発毛または育毛促進効果を発現することができる。 In one aspect, the composition of the present invention exhibits 21-O-angeloylteasapogenol E3 derived from green tea saponin, thereby exhibiting a hair growth or hair growth promoting effect superior to conventional hair restorers. be able to.
また、植物性天然物を使用するため、安全性に優れるので、発毛および育毛を促進するための皮膚外用剤として使用することができ、化粧料組成物、薬学組成物および健康食品組成物等に広く使用することができる。 In addition, because it uses plant natural products, it is excellent in safety, so it can be used as a skin external preparation for promoting hair growth and hair growth, and is a cosmetic composition, pharmaceutical composition, health food composition, etc. Can be widely used for.
他の一側面において、21‐O‐アンゲロイルテアサポゲノールE3を有効成分として含有した組成物は、毛嚢毛乳頭細胞を増殖させる効果を有し、PGE2、IL‐6およびIL‐8の生成を抑制する効果を発現することができる。 In another aspect, the composition containing 21-O-angeloylteasapogenol E3 as an active ingredient has an effect of proliferating hair follicle dermal papilla cells, and is a potentiator of PGE2, IL-6, and IL-8. An effect of suppressing generation can be expressed.
2013年8月30日に出願された韓国特許出願番号10‐2013‐0104230号は、すべての目的で全体が本明細書に参照として含まれる。また、本出願は、その全体が本明細書において参照として含まれる韓国特許出願番号10‐2013‐0104230号の利益を主張する。 Korean Patent Application No. 10-2013-0104230 filed on August 30, 2013 is hereby incorporated by reference in its entirety for all purposes. In addition, this application claims the benefit of Korean Patent Application No. 10-2013-0104230, which is incorporated herein by reference in its entirety.
以下においては、本発明を詳細に説明する。
一側面において、本発明の組成物は、下記化学式1で表されるテアサポゲノール(theasapogenol)誘導体を有効成分として含有する、発毛または育毛促進用組成物である。
In the following, the present invention will be described in detail.
In one aspect, the composition of the present invention is a composition for promoting hair growth or hair growth, which contains a theasapogenol derivative represented by the following chemical formula 1 as an active ingredient.
本発明は、一側面において、発毛または育毛促進が必要な個体に下記化学式1で表されるテアサポゲノール(theasapogenol)誘導体を投与することを含む、発毛または育毛促進方法に関する。前記投与は、本明細書に記載されている投与方法または投与量に従うものであってよい。 In one aspect, the present invention relates to a method for promoting hair growth or hair growth, comprising administering a theasapogenol derivative represented by the following chemical formula 1 to an individual in need of hair growth or hair growth promotion. The administration may be in accordance with the administration method or dosage described herein.
本発明は、一側面において、下記化学式1で表されるテアサポゲノール(theasapogenol)誘導体の発毛または育毛促進用途に関する。 In one aspect, the present invention relates to a hair growth or hair growth promoting application of a theasapogenol derivative represented by the following chemical formula 1.
本発明は、一側面において、発毛または育毛促進に使用するためのものであって、下記化学式1で表されるテアサポゲノール(theasapogenol)誘導体に関する。 In one aspect, the present invention relates to a theasapogenol derivative represented by the following chemical formula 1 for use in hair growth or hair growth promotion.
前記式において、R1およびR2は、それぞれ独立して‐H、C1‐6アルキル、‐OH、‐R6OHまたは‐CHOであり、
R3は、‐H、C1‐6アルキル、‐OHまたは‐OOCR7であり、
R4は、‐Hまたは‐COR8であり、
R5は、‐HまたはC1‐6アルキルであり、
ここで、R6は、C1‐6アルキル、R7は、C2‐6アルケニル、およびR8は、C1‐6アルキルである。
In the above formula, R 1 and R 2 are each independently —H, C 1-6 alkyl, —OH, —R 6 OH or —CHO,
R 3 is —H, C 1-6 alkyl, —OH or —OOCR 7 ;
R 4 is —H or —COR 8 ;
R 5 is —H or C 1-6 alkyl;
Here, R 6 is C 1-6 alkyl, R 7 is C 2-6 alkenyl, and R 8 is C 1-6 alkyl.
他の一側面において、本発明の組成物は、21‐O‐アンゲロイルテアサポゲノールE3を含む、発毛または育毛促進用組成物である。 In another aspect, the composition of the present invention is a composition for promoting hair growth or hair growth comprising 21-O-angeloyl theasapogenol E3.
本発明は、一側面において、発毛または育毛促進が必要な個体に21‐O‐アンゲロイルテアサポゲノールE3を投与することを含む、発毛または育毛促進方法に関するものであってよい。前記投与は、本明細書に記載されている投与方法または投与量に従うものであってよい。 In one aspect, the present invention may relate to a method for promoting hair growth or hair growth, comprising administering 21-O-angeloylteasapogenol E3 to an individual in need of hair growth or hair growth promotion. The administration may be in accordance with the administration method or dosage described herein.
本発明は、一側面において、21‐O‐アンゲロイルテアサポゲノールE3の発毛または育毛促進用途に関するものであってよい。 In one aspect, the present invention may relate to a hair growth or hair growth promoting application of 21-O-angeloylteasapogenol E3.
本発明は、一側面において、発毛または育毛促進に使用するための21‐O‐アンゲロイルテアサポゲノールE3に関するものであってよい。 In one aspect, the present invention may relate to 21-O-angeloylteasapogenol E3 for use in hair growth or hair growth promotion.
また他の一側面において、前記21‐O‐アンゲロイルテアサポゲノールE3は、下記化学式2で表されるものであってよい。すなわち、下記化学式2は、前記化学式1において、R1が‐CHO、R2が‐CH3、R3が‐OCOC(CH3)=CHCH3、R4が‐COCH3、およびR5が‐CH3であるテアサポゲノール誘導体に相当する。 In another aspect, the 21-O-angeloylteasapogenol E3 may be represented by the following chemical formula 2. That is, the following chemical formula 2 is the formula 1, wherein R 1 is —CHO, R 2 is —CH 3 , R 3 is —OCOC (CH 3 ) ═CHCH 3 , R 4 is —COCH 3 , and R 5 is — Corresponds to a theasapogenol derivative that is CH 3 .
また他の一側面において、前記化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3は、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3であってよい。緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3は、緑茶種子から水または有機溶媒を利用して、サポニンを含有する抽出物を収得するステップ;および、前記抽出物を酸、塩基、酵素または前記酵素を生産する微生物を利用して加水分解することにより、21‐O‐アンゲロイルテアサポゲノールE3を分離するステップを含む製造方法を通じて製造されてよい。 In another aspect, the theasapogenol derivative represented by Chemical Formula 1 or 21-O-angeloyl theasapogenol E3 may be 21-O-angeloyltheasapogenol E3 derived from green tea saponin. . 21-O-Angeloylteasapogenol E3 derived from green tea saponin is obtained from green tea seeds using water or an organic solvent to obtain an extract containing saponin; Alternatively, it may be produced through a production method including a step of separating 21-O-angeloylteasapogenol E3 by hydrolysis using an enzyme or a microorganism producing the enzyme.
前記有機溶媒は、エタノール、メタノール、ブタノール、エーテル、酢酸エチルおよびクロロホルムを含む群から選択された一つ以上の有機溶媒またはこれらと水の混合物、一側面において、50%エタノールを使用してよい。前記酸は、塩酸、硫酸および硝酸からなる群より選択された一つ以上の酸、または前記酸とエタノール、メタノールおよびブタノールからなる群より選択された一つ以上のアルコールとの混合溶媒を使用してよい。前記塩基は、水酸化ナトリウムおよび水酸化カリウムからなる群より選択された一つ以上の塩基、または前記塩基とエタノール、メタノール、ブタノールからなる群より選択された一つ以上のアルコールとの混合溶媒を使用してよい。前記酵素または前記酵素を生産する微生物は、抽出物に含有された緑茶サポニンの糖結合を分解する酵素または前記糖結合を分解する酵素を生産する微生物であって、緑茶サポニンの糖部分を除去して21‐O‐アンゲロイルテアサポゲノールE3を生成することができるものである。また、前記酵素は、グルコシダーゼ(glucosidase)、アラビノシダーゼ(arabinosidase)、ラムノシダーゼ(rhamnosidase)、キシロシダーゼ(xylosidase)、セルラーゼ(cellulase)、ヘスペリジナーゼ(hesperidinase)、ナリンギナーゼ(naringinase)、グルクロニダーゼ(glucuronidase)、ペクチナーゼ(pectinase)、ガラクトシダーゼ(galactosidase)およびアミログルコシダーゼ(amyloglucosidase)からなる群より選択された一つ以上であってよい。さらに、前記酵素を生産する微生物は、アスペルギルス(aspergillus)属、バチルス(bacillus)属、ペニシリウム(penicillium)属、リゾプス(rhizopus)属、リゾムコール(rhizomucor)属、タラロマイセス(talaromyces)属、ビフィドバクテリウム(bifidobacterium)属、モルチエレラ(mortierella)属、クリプトコッカス(cryptococcus)属、ミクロバクテリウム(microbacterium)属からなる群より選択された一つ以上であってよい。 The organic solvent may be one or more organic solvents selected from the group comprising ethanol, methanol, butanol, ether, ethyl acetate, and chloroform, or a mixture thereof and water. In one aspect, 50% ethanol may be used. The acid is one or more acids selected from the group consisting of hydrochloric acid, sulfuric acid and nitric acid, or a mixed solvent of the acid and one or more alcohols selected from the group consisting of ethanol, methanol and butanol. It's okay. The base is one or more bases selected from the group consisting of sodium hydroxide and potassium hydroxide, or a mixed solvent of the base and one or more alcohols selected from the group consisting of ethanol, methanol, and butanol. May be used. The enzyme or the microorganism that produces the enzyme is an microorganism that produces an enzyme that degrades the sugar bond of green tea saponin contained in the extract or an enzyme that degrades the sugar bond, and removes the sugar portion of the green tea saponin. 21-O-angeloyl theasapogenol E3 can be produced. The enzymes include glucosidase, arabinosidase, rhamnosidase, xylosidase, cellulase, hesperidinase, naringase, naringase, naringase, It may be one or more selected from the group consisting of pectinase, galactosidase, and amyloglucosidase. In addition, the microorganisms that produce the enzyme include the genera Aspergillus, Bacillus, Penicillium, Rhizopus, Rhizomucor, Talaromyces, and Talaromyces. It may be one or more selected from the group consisting of the genus (bifidobacterium), the genus Mortierella, the genus cryptococcus, and the genus microbacterium.
前記のように、酸、塩基、酵素、または前記酵素を生産する微生物を利用して加水分解した後、反応液を減圧濃縮して溶媒を除去し、残渣にアルコールを加えて1〜5回攪拌させた後、沈殿した塩等を、濾過を通じて除去し、濾過された濾液を減圧濃縮して粗生成物を収得し、習得された粗生成物をシリカゲルカラムクロマトグラフィー(クロロホルム:メタノール=8:1〜4:1)で分離して、21‐O‐アンゲロイルテアサポゲノールE3を収得してよい。 As described above, after hydrolysis using acid, base, enzyme, or microorganism producing the enzyme, the reaction solution is concentrated under reduced pressure to remove the solvent, and alcohol is added to the residue and stirred 1 to 5 times. Then, precipitated salts and the like are removed through filtration, and the filtrate is concentrated under reduced pressure to obtain a crude product. The obtained crude product is subjected to silica gel column chromatography (chloroform: methanol = 8: 1). ˜4: 1) to obtain 21-O-angeloylteasapogenol E3.
一側面において、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3の製造方法に関する韓国特許出願第10‐2008‐0088127号は、明細書全体が本発明の参照として含まれる。 In one aspect, Korean Patent Application No. 10-2008-0088127 relating to a method for producing 21-O-angeloylteasapogenol E3 derived from green tea saponin is incorporated herein by reference in its entirety.
本明細書に開示される組成物は、一側面において、組成物の総重量を基準として0.001〜20重量%の、化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3を含有してよく、他の一側面において、0.01〜15重量%、0.01〜10重量%、または0.1〜5重量%含有してよい。一側面において、本明細書に開示される組成物に含まれる化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3は、組成物の総重量を基準として0.001重量%以上、0.01重量%以上、0.1重量%以上、または1.0重量%以上であってよく、他の一側面において、20重量%以下、15重量%以下、10重量%以下、または5重量%以下であってよい。含有量が0.001重量%未満である場合には、組成物の発毛または育毛促進効果を期待することができず、20重量%を超過する場合には、安全性または剤形上製造に困難があるが、前記含有量に特に限定されるものではない。 In one aspect, the composition disclosed herein comprises 0.001 to 20% by weight of the theasapogenol derivative represented by Formula 1 or 21-O-angeloylteasapogen based on the total weight of the composition. Nord E3 may be contained, and in another aspect, 0.01 to 15 wt%, 0.01 to 10 wt%, or 0.1 to 5 wt% may be contained. In one aspect, the theasapogenol derivative represented by Formula 1 or 21-O-angeloylteasapogenol E3 contained in the composition disclosed herein is 0.001 weight based on the total weight of the composition % Or more, 0.01% or more, 0.1% or more, or 1.0% or more, and in another aspect, 20% or less, 15% or less, 10% or less, Or it may be 5 weight% or less. When the content is less than 0.001% by weight, the effect of promoting hair growth or hair growth of the composition cannot be expected, and when the content exceeds 20% by weight, it is necessary for safety or dosage form production. Although it is difficult, the content is not particularly limited.
本明細書に開示される組成物は、一側面において、化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3を含み、毛嚢毛乳頭細胞を増殖させる効果を有する組成物であってよい。他の一側面において、本明細書に開示される組成物は、化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3を含み、ケラチン形成細胞を活性化させる組成物であってよい。 The composition disclosed in the present specification, in one aspect, includes a theasapogenol derivative represented by Chemical Formula 1 or 21-O-angeloylteasapogenol E3, and has an effect of proliferating hair follicle papilla cells It can be a thing. In another aspect, the composition disclosed herein comprises a theasapogenol derivative represented by Formula 1 or 21-O-angeloylteasapogenol E3, and activates keratinocytes. It may be.
本明細書に開示される組成物は、他の一側面において、化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3を含み、PGE2、IL‐6またはIL‐8の生成を抑制する効果を有する組成物であってよい。 In another aspect, the composition disclosed herein includes a theasapogenol derivative represented by Formula 1 or 21-O-angeloylteasapogenol E3, wherein PGE2, IL-6, or IL-8 It may be a composition having an effect of suppressing generation.
本発明の発毛または育毛促進用組成物は、一側面において、薬学組成物、化粧料組成物または健康食品組成物であってよい。 In one aspect, the composition for promoting hair growth or hair growth of the present invention may be a pharmaceutical composition, a cosmetic composition, or a health food composition.
本発明の一実施形態に係る発毛または育毛促進用化粧料組成物には、化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3以外に、機能性添加物および一般的な化粧料組成物に含まれる成分がさらに含まれてよい。前記機能性添加物としては、水溶性ビタミン、油溶性ビタミン、高分子ペプチド、高分子多糖、スフィンゴ脂質および海藻エキスからなる群より選択された成分を含んでよい。 The cosmetic composition for promoting hair growth or hair growth according to one embodiment of the present invention includes functional additives and general additives other than the theasapogenol derivative represented by Chemical Formula 1 or 21-O-angeloylteasapogenol E3. Ingredients included in a typical cosmetic composition may be further included. The functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids, and seaweed extracts.
また、本発明の化粧料組成物には、前記機能性添加物とともに、必要に応じて、一般的な化粧料組成物に含まれる成分を配合してよい。その他に含まれる配合成分としては、油脂成分、保湿剤、エモリエント剤、界面活性剤、有機および無機顔料、有機粉体、紫外線吸収剤、防腐剤、殺菌剤、酸化防止剤、植物抽出物、pH調整剤、アルコール、色素、香料、血行促進剤、冷感剤、制汗剤、精製水等を挙げることができる。 Moreover, you may mix | blend the component contained in a general cosmetic composition with the said functional additive with the cosmetic composition of this invention as needed. Other ingredients included are oil and fat ingredients, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, UV absorbers, preservatives, fungicides, antioxidants, plant extracts, pH Examples include regulators, alcohols, pigments, fragrances, blood circulation promoters, cooling sensates, antiperspirants, and purified water.
本発明の一実施形態に係る発毛または育毛促進用化粧料組成物は、剤形が特に限定されず、目的とするところに応じて適切に選択してよい。たとえば、スキンローション、スキンソフナー、スキントナー、アストリンゼント、ローション、ミルクローション、モイスチャーローション、栄養ローション、マッサージクリーム、栄養クリーム、モイスチャークリーム、ハンドクリーム、ファンデーション、エッセンス、栄養エッセンス、パック、石鹸、クレンジングフォーム、クレンジングローション、クレンジングクリーム、ボディローションおよびボディソープからなる群より選択されたいずれか一つ以上の剤形で製造されてよいが、これらに限定されるものではない。 The cosmetic composition for promoting hair growth or hair growth according to one embodiment of the present invention is not particularly limited in dosage form, and may be appropriately selected according to the intended purpose. For example, skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, foundation, essence, nutrition essence, pack, soap, cleansing foam, It may be manufactured in any one or more dosage forms selected from the group consisting of cleansing lotion, cleansing cream, body lotion and body soap, but is not limited thereto.
本発明の剤形がペースト、クリームまたはゲルである場合には、担体成分として、動物繊維、植物繊維、ワックス、パラフィン、澱粉、トラガカント、セルロース誘導体、ポリエチレングリコール、シリコン、ベントナイト、シリカ、タルクまたは酸化亜鉛等が利用されてよい。 When the dosage form of the present invention is a paste, cream or gel, the carrier component is animal fiber, vegetable fiber, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicon, bentonite, silica, talc or oxidized Zinc or the like may be used.
本発明の剤形がパウダーまたはスプレーである場合には、担体成分として、ラクトース、タルク、シリカ、アルミニウムヒドロキシド、カルシウムシリケートまたはポリアミドパウダーが利用されてよく、特に、スプレーの場合には、さらにクロロフルオロヒドロカーボン、プロパン/ブタンまたはジメチルエーテルといった推進体を含んでよい。 When the dosage form of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, especially in the case of a spray. Propellants such as fluorohydrocarbons, propane / butane or dimethyl ether may be included.
本発明の剤形が溶液または乳濁液の場合には、担体成分として、溶媒、溶媒化剤または乳濁化剤が利用されてよく、たとえば、水、エタノール、イソプロパノール、エチルカーボネート、酢酸エチル、ベンジルアルコール、ベンジルベンゾエート、プロピレングリコール、1,3‐ブチルグリコールオイル、グリセロール脂肪族エステル、ポリエチレングリコールまたはソルビタンの脂肪酸エステルがある。 When the dosage form of the present invention is a solution or an emulsion, a solvent, a solvating agent or an emulsifying agent may be used as a carrier component. For example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, There are benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.
本発明の剤形が懸濁液である場合には、担体成分として、水、エタノールまたはプロピレングリコールといった液状希釈剤、エトキシル化イソステアリルアルコール、ポリオキシエチレンソルビトールエステルおよびポリオキシエチレンソルビタンエステルといった懸濁剤、微小結晶性セルロース、アルミニウムメタヒドロキシド、ベントナイト、アガーまたはトラガカント等が利用されてよい。 When the dosage form of the present invention is a suspension, the carrier component is a liquid diluent such as water, ethanol or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester. Agents, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth may be used.
本発明の剤形が界面活性剤含有クレンジングである場合には、担体成分として、脂肪族アルコールソルフェート、脂肪族アルコールエーテルソルフェート、スルホコハク酸モノエステル、イセチオネート、イミダゾリニウム誘導体、メチルタウレート、サルコシネート、脂肪酸アミドエーテルソルフェート、アルキルアミドベタイン、脂肪族アルコール、脂肪酸グリセリド、脂肪酸ジエタノールアミド、植物性油、リノリン誘導体またはエトキシル化グリセロール脂肪酸エステル等が利用されてよい。 When the dosage form of the present invention is a surfactant-containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, Sarcosinates, fatty acid amide ether sulfates, alkylamide betaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives or ethoxylated glycerol fatty acid esters may be used.
化粧料組成物に含まれる有効成分である化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3の含有量は、特に制限されないが、組成物の総重量を基準として0.001〜20重量%であってよく、他の一側面において、0.01〜15重量%、0.01〜10重量%、または0.1〜5重量%であってよい。前記有効成分が前記含量を満たす場合、副作用なしに優れた効能を発現することができる。 The content of the theasapogenol derivative represented by Chemical Formula 1 or 21-O-angeloylteasapogenol E3, which is an active ingredient contained in the cosmetic composition, is not particularly limited, but is 0 based on the total weight of the composition. 0.001 to 20 wt%, and in another aspect 0.01 to 15 wt%, 0.01 to 10 wt%, or 0.1 to 5 wt%. When the said active ingredient satisfy | fills the said content, the outstanding effect can be expressed without a side effect.
本発明の一実施形態に係る発毛または育毛促進用薬学組成物は、化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3以外に、防腐剤、安定化剤、水和剤または乳化促進剤、浸透圧調節のための塩および/または緩衝剤等の薬剤学的補助剤、ならびにその他治療的に有用な物質をさらに含有してよく、通常の方法に従って多様な経口投与剤または非経口投与剤の形態で剤形化してよい。 The pharmaceutical composition for promoting hair growth or hair growth according to one embodiment of the present invention comprises a preservative, a stabilizer, water, in addition to the theasapogenol derivative represented by Chemical Formula 1 or 21-O-angeloylteasapogenol E3. It may further contain hydrating agents, emulsifying agents, pharmacological adjuvants such as salts and / or buffers for regulating osmotic pressure, and other therapeutically useful substances, and various oral administrations according to conventional methods The dosage form may be in the form of an agent or a parenteral agent.
前記経口投与剤は、たとえば、錠剤、丸剤、硬質および軟質カプセル剤、液剤、懸濁剤、乳化剤、シロップ剤、粉剤、散剤、細粒剤、顆粒剤、ペレット剤等があり、これらの剤形は、有効成分以外に、界面活性剤、希釈剤(例:ラクトース、デキストロース、スクロース、マンニトール、ソルビトール、セルロースおよびグリシン)、滑沢剤(例:シリカ、タルク、ステアリン酸およびそのマグネシウムまたはカルシウム塩、ならびにポリエチレングリコール)を含有してよい。錠剤は、また、マグネシウムアルミニウムシリケート、澱粉ペースト、ゼラチン、トラガカンス、メチルセルロース、ナトリウムカルボキシメチルセルロースおよびポリビニルピロリジンといった結合剤を含有してよく、場合によって、澱粉、寒天、アルギン酸またはそのナトリウム塩といった崩解剤、吸収剤、着色剤、香味剤、および甘味料等の薬剤学的添加剤を含有してよい。前記錠剤は、通常の混合、顆粒化またはコーティング方法によって製造されてよい。 Examples of the oral administration agent include tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, powders, powders, fine granules, granules, pellets, and the like. In addition to the active ingredient, the form includes surfactants, diluents (eg lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine), lubricants (eg silica, talc, stearic acid and its magnesium or calcium salts) As well as polyethylene glycol). Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally disintegrating agents such as starch, agar, alginic acid or its sodium salt, Pharmaceutical additives such as absorbents, colorants, flavoring agents, and sweeteners may be included. The tablets may be manufactured by conventional mixing, granulating or coating methods.
また、前記非経口投与形態として、経皮投与型剤形であってよく、たとえば、注射剤、点滴剤、軟膏、ローション、ゲル、クリーム、スプレー、懸濁剤、乳剤、坐剤、パッチ等の剤形であってよいが、これらに限定されるものではない。 The parenteral dosage form may be a transdermal dosage form such as an injection, infusion, ointment, lotion, gel, cream, spray, suspension, emulsion, suppository, patch, etc. The dosage form may be, but is not limited to these.
本発明の一実施例に係る前記薬学組成物は、非経口、直腸、局所、経皮、皮下等に投与されてよい。本発明の一実施例に係る薬学組成物は、たとえば、頭皮に局所投与されてよい。 The pharmaceutical composition according to one embodiment of the present invention may be administered parenterally, rectally, topically, transdermally, subcutaneously, and the like. The pharmaceutical composition according to one embodiment of the present invention may be locally administered to the scalp, for example.
前記有効成分の投与量の決定は、当業者の水準内にあり、薬物の1日投与量は、投与しようとする対象の脱毛進行程度、発症時期、年齢、健康状態、合併症等の多様な要因に応じて異なるが、成人を基準とした場合、一側面において前記組成物1μg/kg〜200mg/kg、他の一側面において50μg/kg〜50mg/kgを、1日1〜3回に分割して投与してよく、前記投与量は、いかなる方法であれ、本発明の範囲を限定するものではない。 Determination of the dose of the active ingredient is within the level of those skilled in the art, and the daily dose of the drug varies depending on the degree of hair loss progression, onset time, age, health status, complications, etc. of the subject to be administered. Although it depends on factors, in the case of adults as a reference, the composition is divided into 1 μg / kg to 200 mg / kg in one aspect and 50 μg / kg to 50 mg / kg in one aspect divided into 1 to 3 times a day. The dosage is not intended to limit the scope of the invention in any way.
また、前記本発明の一実施例に係る発毛および育毛促進用組成物は、皮膚外用剤であってよく、前記皮膚外用剤は、皮膚外部において塗布されるいかなるものであっても含まれ得る総称であって、多様な剤形の化粧品、医薬品がここに含まれてよい。 Further, the composition for promoting hair growth and hair growth according to one embodiment of the present invention may be an external preparation for skin, and the external preparation for skin may be included in any form applied outside the skin. It is a generic term and may include cosmetics and pharmaceuticals in various dosage forms.
本発明の一実施例に係る健康食品組成物において、前記組成物は、液状または固体状態の剤形であってよく、錠剤、カプセル剤、軟質カプセル剤、丸剤、顆粒剤、飲料(ドリンク剤)、ダイエットバー、チョコレート、キャラメル剤形または菓子類の剤形であってよく、その剤形が特に限定されるものではない。本発明の健康食品組成物は、21‐O‐アンゲロイルテアサポゲノールE3である有効成分以外にも、必要に応じて、賦形剤、糖類、香料、色素、油脂類、タンパク質などを適宜含有してよい。 In the health food composition according to one embodiment of the present invention, the composition may be in a liquid or solid dosage form, and is a tablet, capsule, soft capsule, pill, granule, beverage (drink agent) ), Diet bar, chocolate, caramel dosage form or confectionery dosage form, and the dosage form is not particularly limited. In addition to the active ingredient 21-O-angeloylteasapogenol E3, the health food composition of the present invention appropriately contains excipients, saccharides, fragrances, pigments, oils and fats, proteins and the like as necessary. May be included.
健康食品組成物に含まれる有効成分である化学式(1)で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3の含量は、特に制限されないが、組成物の総重量を基準として0.001〜20重量%であってよく、他の一側面において、0.01〜15重量%、0.01〜10重量%、または0.1〜5重量%であってよい。前記有効成分が前記含量を満たす場合、副作用なしに優れた効能を発現することができる。 The content of theasapogenol derivative represented by chemical formula (1) or 21-O-angeloylteasapogenol E3, which is an active ingredient contained in the health food composition, is not particularly limited, but is based on the total weight of the composition It may be 0.001 to 20% by weight, and in another aspect may be 0.01 to 15% by weight, 0.01 to 10% by weight, or 0.1 to 5% by weight. When the said active ingredient satisfy | fills the said content, the outstanding effect can be expressed without a side effect.
以下の実施例を通じて本発明をより詳細に説明する。ただし、実施例は、本発明を例示するためのものであって、これらのみに本発明の範囲が限定されるものではない。 The present invention will be described in more detail through the following examples. However, the examples are for illustrating the present invention, and the scope of the present invention is not limited to these examples.
[製造例1]緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3の製造
緑茶種子2kgにヘキサン6リットルを入れ、常温で攪拌抽出して脱脂させた後、脱脂された緑茶種子1kgに50%エタノール4リットルを入れ、3回還流抽出した後、15℃で1日間浸漬させた。その後、濾過布濾過と遠心分離を通じて残渣と濾液を分離し、分離されたろ液を減圧濃縮して得たエキスを水に懸濁した後、エーテル1リットルで5回抽出して色素を除去し、水層を1‐ブタノール500mlで3回抽出した。これから得られた総1‐ブタノール層を減圧濃縮して1‐ブタノールエキスを得、これを少量のメタノールに溶かした後、大量のエチルアセテートに追加して、生成された沈殿物を乾燥することにより、緑茶種子抽出物300gを得た。
[Production Example 1] Manufacture of 21-O-angeloylteasapogenol E3 derived from green tea saponin 6 kg of hexane was added to 2 kg of green tea seeds, stirred and extracted at room temperature, and then defatted, 1 kg of defatted green tea seeds 4 liters of 50% ethanol was added to the solution, and the mixture was extracted by refluxing three times and then immersed at 15 ° C. for 1 day. Thereafter, the residue and the filtrate are separated through filtration with a cloth filter and centrifugal separation, and the extract obtained by concentrating the separated filtrate under reduced pressure is suspended in water, and then extracted 5 times with 1 liter of ether to remove the pigment. The aqueous layer was extracted 3 times with 500 ml of 1-butanol. The total 1-butanol layer obtained from this was concentrated under reduced pressure to obtain 1-butanol extract, which was dissolved in a small amount of methanol, added to a large amount of ethyl acetate, and the resulting precipitate was dried. 300 g of green tea seed extract was obtained.
前記得られた緑茶種子抽出物10gに、20倍(v/w)の1N HCl‐50%メタノール溶液(v/v)を加え、80℃水浴槽で8時間加熱還流させて、緑茶種子粗サポニンに結合された糖を加水分解させた。反応液を減圧濃縮して溶媒を除去し、残渣にエタノール(200ml)を加えて攪拌した後(3回)、濾過を通じて沈殿した塩等を除去した後、ろ過されたろ液を減圧濃縮して粗生成物を収得した後、収得された粗生成物をシリカゲルカラムクロマトグラフィー(クロロホルム:メタノール=7:1〜3:1)で分離して、21‐O‐アンゲロイルテアサポゲノールE3 0.55を収得した。Varian Gemini 2000 300MHz(Varian社)を利用して、前記収得物が21‐O‐アンゲロイルテアサポゲノールE3であるか確認したところ、本明細書において参照している韓国特許出願第10‐2008‐0088127号の発明の詳細な説明の実験例1と同一の結果が出た。 To 10 g of the obtained green tea seed extract, 20 times (v / w) 1N HCl-50% methanol solution (v / v) is added and heated to reflux in an 80 ° C. water bath for 8 hours to obtain green tea seed crude saponin. The sugar bound to was hydrolyzed. The reaction solution was concentrated under reduced pressure to remove the solvent. Ethanol (200 ml) was added to the residue and stirred (3 times), and then the precipitated salt and the like were removed through filtration. The filtered filtrate was concentrated under reduced pressure to obtain a crude product. After obtaining the product, the obtained crude product was separated by silica gel column chromatography (chloroform: methanol = 7: 1 to 3: 1) to give 21-O-angeloylteasapogenol E3 0.55. Was obtained. Using Varian Gemini 2000 300 MHz (Varian), it was confirmed that the obtained product was 21-O-angeloylteasapogenol E3. Korean Patent Application No. 10-2008 referred to in this specification is used. The same results as in Experimental Example 1 in the detailed description of the invention of -0088127 were obtained.
[試験例1]毛乳頭細胞における毛髪成長因子VEGFの発現評価
21‐O‐アンゲロイルテアサポゲノールE3が、血管形成に必要な成長因子であって毛髪の成長期に移動するのに必要な成長因子である血管内皮増殖因子(Vascular endothelial growth factor;VEGF)を発現させる程度を評価するために、生体外(in vitro)システムを適用して、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3適用後の活性を評価した。
[Test Example 1] Expression evaluation of hair growth factor VEGF in dermal papilla cells 21-O-angeloylteasapogenol E3 is a growth factor necessary for angiogenesis and is required to move to the hair growth phase In order to evaluate the degree of expression of the growth factor vascular endothelial growth factor (VEGF), an in vitro system was applied to apply 21-O-angeloyltea derived from green tea saponin. The activity after application of sapogenol E3 was evaluated.
前記実験のために、47歳の男性の毛乳頭真皮細胞(Dermal Papilla Cell;DPC)(P.11)4×105cellを、12ウェルプレート(well plate)にシーディング(seeding)し、10%FBS(fetal bovine serum)を含有するDMEM(Dulbecco´s modified Eagle´s medium)培地において一晩培養した。培養後、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3を20ppmで処理した。陰性対照群としては、DMSOを使用した。24時間後、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3が処理された混合液を収集(soup collect)し、VEGF ELISA(Vascular endothelial growth factor Enzyme‐Linked Immunosorbent Assay;R&D biosystems)を使用して、緑茶サポニンから由来された21‐O‐アンゲロイルテアサポゲノールE3の発現程度を確認した。そして、その結果を表1に示した。 For the experiment, 47-year-old male dermal papilla dermal cells (DPC) (P.11) 4 × 10 5 cells were seeded into a 12-well plate, 10 The cells were cultured overnight in DMEM (Dulbecco's modified Eagle's medium) medium containing% FBS (fetal bovine serum). After the cultivation, 21-O-angeloylteasapogenol E3 derived from green tea saponin was treated with 20 ppm. DMSO was used as a negative control group. 24 hours later, a mixed solution treated with 21-O-angeloylteasapogenol E3 derived from green tea saponin was collected (soap collect), and VEGF ELISA (Vascular endogenous growth factor & Linked ImmediateRimbsorbyImmunosbMimsorbentImmunsorbentImmunosminDimRimbMimBossImmunBossImmunBossImmunBossImmunBossImmunBossImmunBossImmunoBloodImmunoSimogen) Was used to confirm the expression level of 21-O-angeloylteasapogenol E3 derived from green tea saponin. The results are shown in Table 1.
表1から見られるように、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3は、対照群と比較して大きな効果の差が現れたことを確認することができ、毛乳頭細胞における毛髪成長因子VEGFの発現を約3倍以上増加させた。したがって、本発明に係る緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3は、優れた毛髪生成促進能を有することが分かる。 As can be seen from Table 1, it can be confirmed that 21-O-angeloylteasapogenol E3 derived from green tea saponin showed a large difference in effect compared with the control group, Increased the expression of hair growth factor VEGF in about 3 times or more. Therefore, it can be seen that 21-O-angeloylteasapogenol E3 derived from the green tea saponin according to the present invention has an excellent ability to promote hair generation.
[試験例2]毛嚢毛乳頭細胞増殖効果の評価
毛髪を構成するケラチンタンパク質は、毛根部ケラチン形成細胞(keratinocyte)で生成され、このケラチン形成細胞は、毛乳頭細胞から分化される。したがって、本発明に係る緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3が毛乳頭細胞の活性を促進するのであれば、それから分化されるケラチン形成細胞の活性を促進させることができ、ひいては毛髪生成を促進することができるであろう。
[Test Example 2] Evaluation of hair follicle dermal papilla cell proliferation effect Keratin protein constituting hair is produced by hair root keratinocytes, and these keratinocytes are differentiated from dermal papilla cells. Therefore, if 21-O-angeloylteasapogenol E3 derived from the green tea saponin according to the present invention promotes the activity of hair papilla cells, the activity of keratinocytes differentiated therefrom can be promoted. , And thus hair production could be promoted.
そこで、本実験では、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3の毛乳頭細胞活性促進効果を、下記のように評価した。 Therefore, in this experiment, the effect of 21-O-angeloylteasapogenol E3 derived from green tea saponin on promoting dermal papilla cell activity was evaluated as follows.
まず、本実験においては、ヒト毛乳頭細胞(Human dermal papilla cell、ソウル大学校・権五祥教授)細胞株を使用した。前記細胞株は、10%ウシ胎児血清(FBS)が含有されたDulbecco´s modified Eagle´s medium(DMEM;Gibco BRL,Gaithersburg,MD,USA)において、5%CO2、37℃で維持されるインキュベータで24時間培養した後、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3を1ppm、10ppmおよび20ppmそれぞれ処理した。陰性対照群としては、DMSOを使用した。試験物質を処理した後、24時間経過後に、WST‐1キット(Roche)を使用して、細胞増殖能(%)を測定した。その結果を表2に示した。 First, in this experiment, a human hair papilla cell (Human derma papilla cell, Seoul National University, Professor Gongosho) cell line was used. The cell lines, Dulbecco's were contained 10% fetal bovine serum (FBS) modified Eagle's medium (DMEM ; Gibco BRL, Gaithersburg, MD, USA) in is maintained at 5% CO 2, 37 ℃ After culturing in an incubator for 24 hours, 21-O-angeloylteasapogenol E3 derived from green tea saponin was treated with 1 ppm, 10 ppm and 20 ppm, respectively. DMSO was used as a negative control group. After the treatment of the test substance, 24 hours later, the cell proliferation ability (%) was measured using the WST-1 kit (Roche). The results are shown in Table 2.
表2から見られるように、本発明に係る緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3は、10ppmおよび20ppmともに、2つの細胞の増殖を有意に増加させた。特に、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3を20ppm処理した場合が、対照群と対比して約1.5倍以上高い毛乳頭細胞増殖増加率を示した。これは、本発明に係る緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3が、毛乳頭細胞の増殖を促進させることができ、ケラチン形成細胞の活性および毛髪の生成もより効果的に促進することができることを意味する。 As can be seen from Table 2, 21-O-angeloylteasapogenol E3 derived from the green tea saponin according to the present invention significantly increased the proliferation of the two cells at both 10 ppm and 20 ppm. In particular, when 20 ppm of 21-O-angeloylteasapogenol E3 derived from green tea saponin was treated with 20 ppm, the growth rate of hair papilla cell proliferation was about 1.5 times higher than that of the control group. This is because 21-O-angeloylteasapogenol E3 derived from the green tea saponin according to the present invention can promote the proliferation of hair papilla cells, and the activity of keratinocytes and the generation of hair are also more effective. Means that can be promoted.
[試験例3]人体毛嚢器官を利用した毛髪成長促進効果の評価
本発明の、実際の人体毛嚢器官における毛髪成長促進能を確認した実験を実施した。
[Test Example 3] Evaluation of hair growth promoting effect using human hair follicle organ An experiment was conducted in which the hair growth promoting ability of an actual human hair follicle organ according to the present invention was confirmed.
55歳の男性の後頭部頭皮組織から毛嚢器官を一つずつ分離して、William E培地(L‐グルタミン(2mM)、インスリン(10μg/ml)、ヒドロコルチゾン(40ng/ml)、抗生剤(1%)、抗真菌剤(1%)含有)に培養した。培養後3日目に成長が起こった毛嚢を選別して3mmに切り、選別した毛嚢組織に対して、薬物を処理していない場合を対照群とし、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3 1ppm、3ppmおよび5ppmをそれぞれ処理した。そして、処理してから8日後、それぞれの長さの測定および写真撮影を行った。その結果を表3に示した。 Hair follicle organs were isolated one by one from a 55-year-old male occipital scalp tissue, and William E medium (L-glutamine (2 mM), insulin (10 μg / ml), hydrocortisone (40 ng / ml), antibiotics (1% ) And an antifungal agent (containing 1%). The hair follicles that grew on the third day after the culture were selected and cut into 3 mm, and the selected hair follicle tissue was treated with 21-O- derived from green tea saponin as a control group. Angeloylteaasapogenol E3 1 ppm, 3 ppm and 5 ppm were treated, respectively. And 8 days after processing, each length was measured and photographed. The results are shown in Table 3.
その結果、表3から見られるように、毛嚢器官における毛髪の長さの増加において、緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3を5ppm処理した場合は、対照群よりも優れた毛髪成長促進効果が示された。したがって、前記表3の結果を見た場合、本発明に係る緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3は、毛嚢において毛髪の長さの成長を促進する効果に優れることが分かる。 As a result, as can be seen from Table 3, in the increase in hair length in the hair follicle organs, when 5 ppm of 21-O-angeloylteasapogenol E3 derived from green tea saponin was treated, compared to the control group Excellent hair growth promoting effect was shown. Accordingly, when looking at the results in Table 3, the 21-O-angeloylteasapogenol E3 derived from the green tea saponin according to the present invention is excellent in the effect of promoting hair length growth in the hair follicle. I understand.
[試験例4]PGE2、IL‐6およびIL‐8生成抑制実験
ヒト線維芽細胞を6ウェル培養プレートに1×105の細胞濃度で接種し、24時間の間、37℃、5%CO2インキュベータで培養した。H2O2 500μMをウェルに処理して24時間刺激を与えた後、カルシウムの木抽出物を濃度別に処理して48時間反応させた。反応完了後、培養液を回収してELISA分析を行った。このとき、抗炎および刺激緩和剤として多く使用される物質であるα‐ビサボロール(α‐bisaborol)を対照群として使用した。PGE2は、アッセイデザイン(Assay Design)社のキット、IL‐6、IL‐8は、エンドゲン(Endogen)社のキットを使用し、各会社のマニュアルに明記された方法に従って実験を行った。抑制効果は、下記数式1に基づいて計算し、測定結果は、下記表4に示した。
[Test Example 4] PGE2, IL-6, and IL-8 production inhibition experiment Human fibroblasts were inoculated into a 6-well culture plate at a cell concentration of 1 × 10 5 and maintained at 37 ° C. and 5% CO 2 for 24 hours. Cultured in an incubator. The wells were treated with 500 μM H 2 O 2 and stimulated for 24 hours, and then the calcium tree extract was treated according to concentration and reacted for 48 hours. After completion of the reaction, the culture solution was collected and subjected to ELISA analysis. At this time, α-bisabolol, which is a substance frequently used as an anti-inflammatory and stimulating agent, was used as a control group. PGE2 was assayed using Assay Design kit, IL-6 and IL-8 were using Endogen kit, and experiments were performed according to the methods specified in each company's manual. The suppression effect was calculated based on Equation 1 below, and the measurement results are shown in Table 4 below.
下記表4に示されたところのように、炎症媒介物質であるPGE2、IL‐6、IL‐8の生成量が、本発明の緑茶サポニンから由来した21‐O‐アンゲロイルテアサポゲノールE3添加によって著しく減少して、高い抑制効果を示すことを確認することができる。 As shown in Table 4 below, the amount of inflammation mediators PGE2, IL-6, and IL-8 produced was 21-O-angeloylteasapogenol E3 derived from the green tea saponin of the present invention. It can be confirmed that it is remarkably reduced by addition and shows a high inhibitory effect.
[数式1]
抑制効果={1−(試験試料−対照群)/(H2O2−対照群)}×100
[Formula 1]
Inhibitory effect = {1- (test sample-control group) / (H 2 O 2 -control group)} × 100
下記に、本発明に係る組成物の剤形例について説明するが、他の様々な剤形へも応用可能であり、これは、本発明を限定しようとするものではなく、ただ具体的に説明しようとするものである。 Examples of dosage forms of the composition according to the present invention will be described below. However, the present invention can be applied to various other dosage forms, and this is not intended to limit the present invention, but only specifically. It is something to try.
[剤形例1]シャンプー
下記表5に記載された組成に従って、通常の方法でシャンプーを製造した。
[Dosage Form Example 1] Shampoo According to the composition described in Table 5 below, a shampoo was produced by an ordinary method.
[剤形例2]リンス
下記表6に記載された組成に従って、通常の方法でリンスを製造した。
[Dosage Form Example 2] Rinse According to the composition described in Table 6 below, a rinse was produced by an ordinary method.
[剤形例3]軟膏
下記表7に記載された組成に従って、通常の方法で軟膏を製造した。
[Dosage Form Example 3] Ointment An ointment was produced by a conventional method according to the composition described in Table 7 below.
[剤形例4]ヘアトニック
下記表8に記載された組成に従って、通常の方法でヘアトニックを製造した。
[Dosage Form Example 4] Hair Tonic According to the composition described in Table 8 below, a hair tonic was produced by an ordinary method.
[剤形例5]ヘアローション
下記表9に記載された組成に従って、通常の方法でヘアローションを製造した。
[Dosage Form Example 5] Hair Lotion According to the composition described in Table 9 below, a hair lotion was produced by an ordinary method.
[剤形例6]ヘアソープ
下記表10に記載された組成に従って、通常の方法でヘアソープを製造した。
[Dosage Form Example 6] Hair Soap According to the composition described in Table 10 below, a hair soap was produced by an ordinary method.
[剤形例7]ローション
下記表11に記載された組成に従って、通常の方法でローションを製造した。
[Dosage Form Example 7] Lotion According to the composition described in Table 11 below, a lotion was produced by an ordinary method.
[剤形例8]クリーム
下記表12に記載された組成に従って、通常の方法でクリームを製造した。
[Dosage Form Example 8] Cream According to the composition described in Table 12 below, a cream was produced by an ordinary method.
[剤形例9]パック
下記表13に記載された組成に従って、通常の方法でパックを製造した。
[Dosage Form Example 9] Pack According to the composition described in Table 13 below, a pack was produced by an ordinary method.
[剤形例10]美容液型製剤
下記表14に記載された組成に従って、通常の方法で美容液型製剤を製造した。
[Dosage Form Example 10] Cosmetic liquid formulation A cosmetic liquid formulation was produced in the usual manner according to the composition described in Table 14 below.
[剤形例11]軟質カプセル剤
化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3 50mg、L‐カルニチン80〜140mg、大豆油180mg、パーム油2mg、植物性硬化油8mg、黄蝋4mgおよびレシチン6mgを混合し、通常の方法に従って、1カプセルあたり400mgずつ充填して軟質カプセルを製造した。
[Formulation Example 11] Soft Capsule Theasapogenol derivative represented by Chemical Formula 1 or 21-O-angeloylteasapogenol E3 50 mg, L-carnitine 80-140 mg, soybean oil 180 mg, palm oil 2 mg, vegetable hardened oil 8 mg, 4 mg of yellow wax and 6 mg of lecithin were mixed, and 400 mg per capsule was filled according to a normal method to produce soft capsules.
[剤形例12]精製
化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3 50mg、ガラクトオリゴ糖200mg、乳糖60mgおよび麦芽糖140mgを混合し、流動層乾燥機を利用して顆粒した後、糖エステル(sugar ester)6mgを添加して、打錠機で打錠して錠剤を製造した。
[Dosage Form Example 12] Purification A theasapogenol derivative represented by the chemical formula 1 or 21-O-angeloylteasapogenol E3 50 mg, galactooligosaccharide 200 mg, lactose 60 mg and maltose 140 mg are mixed, using a fluid bed dryer. After granulation, 6 mg of sugar ester was added and tableted by a tableting machine to produce tablets.
[剤形例13]顆粒剤
化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3 50mg、無水結晶ブドウ糖250mgおよび澱粉550mgを混合し、流動層造粒機を使用して顆粒に成形した後、包に充填して顆粒剤を製造した。
[Formulation Example 13] Granules Theasapogenol derivative represented by Chemical Formula 1 or 21-O-angeloylteasapogenol E3 50 mg, anhydrous crystalline glucose 250 mg and starch 550 mg were mixed, and using a fluid bed granulator. After forming into granules, the capsules were filled to produce granules.
[剤形例14]ドリンク剤
化学式1で表されるテアサポゲノール誘導体または21‐O‐アンゲロイルテアサポゲノールE3 50mg、ブドウ糖10g、クエン酸0.6gおよび液状オリゴ糖25gを混合した後、精製水300mlを加えて各瓶に200mlずつ充填した。瓶に充填した後、130℃で4〜5秒間殺菌して、ドリンク剤飲料を製造した。
[Formulation Example 14] Drink agent After mixing 50 mg of theasapogenol derivative or 21-O-angeloylteasapogenol E3 represented by chemical formula 1, glucose 10 g, citric acid 0.6 g and liquid oligosaccharide 25 g, purified water 300 ml was added and 200 ml was filled into each bottle. After filling the bottle, it was sterilized at 130 ° C. for 4 to 5 seconds to produce a drink beverage.
Claims (8)
前記組成物は、前記21‐O‐アンゲロイルテアサポゲノール(21‐O‐angeloyltheasapogenol)E3を、前記組成物の総重量を基準として、0.001〜20重量%含有する、発毛または育毛促進用組成物。 A composition containing 21-O-angeloyltheasapogenol E3 as an active ingredient ,
The composition contains the 21-O-angeloyltheasapogenol E3 in an amount of 0.001 to 20% by weight based on the total weight of the composition. Accelerating composition.
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KR10-2013-0104230 | 2013-08-30 | ||
PCT/KR2014/007768 WO2015030422A1 (en) | 2013-08-30 | 2014-08-21 | Composition for accelerating hair restoration or hair growth, comprising 21-o-angeloyltheasapogenol e3 |
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JP2016538842A Active JP6386053B2 (en) | 2013-08-30 | 2014-08-21 | Hair growth or hair growth promoting composition containing 21-O-angeloyl theasapogenol E3 |
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KR (1) | KR102061716B1 (en) |
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KR101957849B1 (en) * | 2015-03-31 | 2019-03-15 | (주)아모레퍼시픽 | Composition for promoting hair growth or restoration and anti-inflammatory composition |
KR102406000B1 (en) * | 2015-09-30 | 2022-06-08 | (주)아모레퍼시픽 | Composition for promoting hair growth and/or restoration containing soyasaponin |
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US5723149A (en) | 1990-11-21 | 1998-03-03 | Lvmh Recherche | Use of medicago saponins for the preparation of cosmetic or pharmaceutical compositions, especially dermatological compositions, promoting renewal of the epidermis, stimulating hair regrowth or delaying hair loss |
FR2695561B1 (en) | 1992-09-17 | 1994-12-02 | Lvmh Rech Gie | Cosmetic or dermatological composition containing at least one ginsenoside-type saponin, and its applications, in particular for hair care. |
CN1144082A (en) * | 1995-08-25 | 1997-03-05 | 蔡汉宏 | Tea seed hair-washing powder preparation technology |
US20020013294A1 (en) * | 2000-03-31 | 2002-01-31 | Delong Mitchell Anthony | Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives |
US20070129430A1 (en) * | 2003-10-07 | 2007-06-07 | Satomi Miyata | Agent for enhancing the production of collagen, their preparation and use |
CN101336970B (en) * | 2008-08-18 | 2012-02-15 | 盛立新 | Chinese herbal medicine for treating and preventing poliosis and alopecia |
KR101415995B1 (en) * | 2008-09-08 | 2014-07-08 | (주)아모레퍼시픽 | Method for preparing green tea saponin, 21-O-angeloyltheasapogenol E3 |
US20120277308A1 (en) * | 2010-07-16 | 2012-11-01 | Pacific Arrow Limited | compounds for treating cancer and other diseases |
KR101204034B1 (en) * | 2010-04-06 | 2012-11-27 | 박승덕 | Cosmetic composition for preventing hair loss and stimulating hair growth and Method for preparing the same |
KR101914157B1 (en) * | 2011-08-24 | 2018-12-31 | (주)아모레퍼시픽 | Cosmetic composition comprising camellia sinensis constituents |
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CN105636593B (en) | 2018-09-18 |
CN105636593A (en) | 2016-06-01 |
WO2015030422A9 (en) | 2016-03-24 |
WO2015030422A1 (en) | 2015-03-05 |
KR102061716B1 (en) | 2020-01-02 |
KR20150025984A (en) | 2015-03-11 |
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