KR101151555B1 - Composition comprising the extract of Acanthopanax koreanum Nakai or the novel compound derived therefrom for preventing baldness and improving hair growth - Google Patents

Composition comprising the extract of Acanthopanax koreanum Nakai or the novel compound derived therefrom for preventing baldness and improving hair growth Download PDF

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KR101151555B1
KR101151555B1 KR1020090037164A KR20090037164A KR101151555B1 KR 101151555 B1 KR101151555 B1 KR 101151555B1 KR 1020090037164 A KR1020090037164 A KR 1020090037164A KR 20090037164 A KR20090037164 A KR 20090037164A KR 101151555 B1 KR101151555 B1 KR 101151555B1
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김영호
강희경
김상철
강정일
유은숙
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충남대학교산학협력단
제주대학교 산학협력단
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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    • A61K36/25Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/254Acanthopanax or Eleutherococcus
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    • A23LFOODS, 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
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    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00Preparations for affecting hair growth

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Abstract

본 발명은 섬오갈피나무 추출물 또는 이로부터 분리한 신규화합물을 유효성분으로 함유하는 탈모 방지 및 모발 생장 촉진 효과를 갖는 조성물에 관한 것으로, 상세하게는 본 발명의 섬오갈피나무 추출물 또는 이로부터 분리한 신규화합물 acankoreoside J가 모발의 성장에 중요한 역할을 하는 모유두세포(Dermal papilla cell)의 성장 증식을 촉진하여 모낭의 성장기를 유도하는 효과를 나타내므로, 탈모 방지 및 발모 개선용 피부외용 약학 조성물 및 화장료 조성물로 이용될 수 있다.The present invention relates to a composition having a hair loss prevention and hair growth promoting effect containing an extract of the islands of Aeolian Islands or a novel compound isolated therefrom. As the compound acankoreoside J promotes the growth and proliferation of dermal papilla cells, which play an important role in hair growth, and induces the growth phase of hair follicles, it is used as an external skin pharmaceutical composition and cosmetic composition for preventing hair loss and improving hair growth. Can be used.

섬오갈피나무, acankoreoside J, 모낭, 탈모, 모유두세포 Isle of Oak Tree, acankoreoside J, hair follicle, hair loss, dermal papilla cells

Description

섬오갈피나무 추출물 또는 이로부터 분리한 신규화합물을 유효성분으로 함유하는 탈모 방지 및 발모 개선용 조성물{Composition comprising the extract of Acanthopanax koreanum Nakai or the novel compound derived therefrom for preventing baldness and improving hair growth}Composition comprising the extract of Acanthopanax koreanum Nakai or the novel compound derived therefrom for preventing baldness and improving hair growth}

본 발명은 섬오갈피나무 추출물 또는 이로부터 분리한 신규화합물을 유효성분으로 함유하는 탈모 방지 및 발모 개선용 조성물에 관한 것이다.The present invention relates to a composition for preventing hair loss and improving hair growth, which contains an extract of S. aureum or a novel compound isolated therefrom as an active ingredient.

[문헌 1] Elliott K, et al ., Differences in hair follicle dermal papilla volume are due to extracellular matrix volume and cell number: implications for the control of hair follicle size and androgen responses., J Invest Dermatol, 113, pp.873-877, 1999[Reference 1] Elliott K, et al . , Differences in hair follicle dermal papilla volume are due to extracellular matrix volume and cell number: implications for the control of hair follicle size and androgen responses., J Invest Dermatol , 113 , pp. 873-877, 1999

[문헌 2] Kaufman KD., Androgens and alopecia., Mol Cell Endocrinol, 198, pp.89-95, 2002[2] Kaufman KD., Androgens and alopecia., Mol Cell Endocrinol , 198 , pp.89-95, 2002

[문헌 3] Botchkarev VA., Molecular mechanisms of chemotherapy-induced hair loss., J Investig Dermatol Symp Proc, 8, pp.72-75, 2003Botchkarev VA., Molecular mechanisms of chemotherapy-induced hair loss., J Investig Dermatol Symp. Proc , 8 , pp. 72-75, 2003

[문헌 4] Botchkarev VA., Stress and the hair follicle: Exploring the connections., Am J Pathol, 162, pp.709-712, 2003[4] Botchkarev VA., Stress and the hair follicle: Exploring the connections., Am J Pathol , 162 , pp. 709-712, 2003

[문헌 5] Han JH, et al., Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle., J Dermatol Sci, 34, pp.91-98, 2004[Reference 5] Han JH, et al ., Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle., J Dermatol Sci , 34 , pp.91-98, 2004

[문헌 6] Kaufman KD, et al ., Finasteride, a Type 2 5alpha-reductase inhibitor, in the treatment of men with androgenetic alopecia., Expert Opin Investig Drugs, 8, pp.403-415, 1999[Reference 6] Kaufman KD, et al . , Finasteride, a Type 2 5alpha-reductase inhibitor, in the treatment of men with androgenetic alopecia., Expert Opin Investig Drugs , 8 , pp. 403-415, 1999

[문헌 7] Botchkarev VA, et al., Molecular control of epithelial- mesenchymal interactions during hair follicle cycling., J Investig Dermatol Symp Proc, 8, pp.46-55, 2003Document 7 Botchkarev VA, et al ., Molecular control of epithelial- mesenchymal interactions during hair follicle cycling., J Investig Dermatol Symp Proc , 8 , pp. 46-55, 2003

[문헌 8] Ozeki M, et al., In vivo promoted growth of mice hair follicles by the controlled release of growth factors., Biomaterials, 24, pp.2387-2394, 2003[Reference 8] Ozeki M, et al ., In vivo promoted growth of mice hair follicles by the controlled release of growth factors., Biomaterials , 24 , pp.2387-2394, 2003

[문헌 9] Jang JH, Stimulation of human hair growth by the recombinant human KGF-2. Biotechnol. Lett, 27, pp.749-752, 20059 Jg, Stimulation of human hair growth by the recombinant human KGF-2. Biotechnol. Lett , 27 , pp. 749-752, 2005

[문헌 10] Kamiya T, et al., Hair follicle elongation in organ culture of skin from newborn and adult mice., Dermatol Sci, 17, pp.54-60, 1998Document 10 Kamiya T, et al ., Hair follicle elongation in organ culture of skin from newborn and adult mice., Dermatol Sci , 17 , pp.54-60, 1998

[문헌 11] Hibino T, et al., Role of TGF-β2 in the human hair cycle., J. Dermatol . Sci, 35, pp.9-18, 2004[Reference 11] Hibino T, et al ., Role of TGF-β2 in the human hair cycle., J. Dermatol . Sci , 35 , pp.9-18, 2004

[문헌 12] Moore KA, et al., Stem cells and their niches. Science, 311, pp.1880-1885, 2006Document 12 Moore KA, et al ., Stem cells and their niches. Science , 311 , pp. 1880-1885, 2006

[문헌 13] Jahoda CA, et al ., Induction of hair growth by implantation of cultured dermal papilla cells., Nature, 311, pp.560-562, 1984Document 13 Jahoda CA, et al . , Induction of hair growth by implantation of cultured dermal papilla cells., Nature , 311 , pp.560-562, 1984

[문헌 14] Han DR, et al., Studies on morphological and chemotaxonomy and seco-triterpene glycoside component of korean Acanthopanax spp., Bull . D.. S. Pharm . Sci . Inst, 11, pp.1-66, 1994Document 14 Han DR, et al ., Studies on morphological and chemotaxonomy and seco-triterpene glycoside component of korean Acanthopanax spp., Bull . D .. S. Pharm . Sci . Inst , 11 , pp.1-66, 1994

[문헌 15] 박호기, 가시오갈피의 삽목 번식방법, 약용작물학회지, 2, pp.133-139, 1994[Ref. 15] Park Ho-ki, Cutting and Reproduction Method of Prickly Pear, Korean Journal of Medicinal Crop Science, 2 , pp.133-139, 1994

[문헌 16] Kim YH, et al., Studies on the constituents of Acanthopanax koreanum Nakai(1)., Kor. J. Pharmacogn, 16, pp.151-154, 1985[Reference 16] Kim YH, et al ., Studies on the constituents of Acanthopanax koreanum Nakai (1)., Kor. J. Pharmacogn , 16 , pp. 151-154, 1985

[문헌 17] Hahn DR, et al., A study on the chemical constituents of Acanthopanax koreanum and its pharmacobiological activities., Yakhak Hoeji, 29, pp.357-361, 1985Reference 17 Hahn DR, et al ., A study on the chemical constituents of Acanthopanax koreanum and its pharmacobiological activities., Yakhak Hoeji , 29 , pp.357-361, 1985

[문헌 18] Chung BS, et al., Studies on the constituents of Acanthopanax koreanum Nakai., Kor. J. Pharmacogn, 17, pp.62-66, 1986Reference 18 Chung BS, et al ., Studies on the constituents of Acanthopanax koreanum Nakai., Kor. J. Pharmacogn , 17 , pp. 62-66, 1986

[문헌 19] Kim YH, et al., Studies on the chemical constituents of Acanthopanax koreanum , Arch. Pharm . Res, 11, pp.159-162, 1988[Reference 19] Kim YH, et al ., Studies on the chemical constituents of Acanthopanax koreanum , Arch. Pharm . Res , 11 , pp. 159-162, 1988

[문헌 20] Kim YH, et al., Pimaradine diterpenes from Acanthopanax koreanum . J. Nat . Prod, 51, pp.1080-1082, 1988[Reference 20] Kim YH, et al ., Pimaradine diterpenes from A canthopanax koreanum . J. Nat . Prod , 51 , pp.1080-1082, 1988

[문헌 21] Kim YH, et al., Diterpene glycoside form Acanthopanax koreanum., Kor. J. Pharmacogn, 21, pp.49-51, 1990[Reference 21] Kim YH, et al ., Diterpene glycoside form Acanthopanax koreanum ., Kor. J. Pharmacogn , 21 , pp. 49-51, 1990

[문헌 22] Choi HS, et al., Lupane glycosides from the leaves of Acanthopanax koreanum., Chem. Pharm . Bull, 56, pp.1613-1616, 2008[Reference 22] Choi HS, et al ., Lupane glycosides from the leaves of Acanthopanax koreanum , Chem. Pharm . Bull , 56 , pp. 1613-1616, 2008

[문헌 23] Perry LM, et al., Medicinal Plants of East and Southeast Asia. MIT Press, Cambrige, p.41, 1980Reference 23 Perry LM, et al ., Medicinal Plants of East and Southeast Asia. MIT Press, Cambrige, p. 41, 1980

[문헌 24] Filsell W, et al., Transfection of rat dermal papilla cells with a gene encoding a temperature-sensitive polyomavirus large T antigen generates cell lines a differentiated phenotype., J. Cell Sci, 107, pp.1761-1772, 1994 [24] Filsell W, et al ., Transfection of rat dermal papilla cells with a gene encoding a temperature-sensitive polyomavirus large T antigen generates cell lines a differentiated phenotype., J. Cell Sci , 107 , pp.1761-1772, 1994

[문헌 25] Philpott MP, et al., Cyclical changes in rat vibrissa follicles maintained in vitro. J Invest Dermatol . 115, pp.1152-1155, 2000[25] Philpott MP, et al ., Cyclical changes in rat vibrissa follicles maintained in in vitro . J Invest Dermatol . 115 , pp. 1152-1155, 2000

최근 몇 십년동안 탈모 치료를 위한 많은 연구가 진행되고 있지만, 아직도 탈모의 원인이 무엇인지는 정확히 알려져 있지는 않다. 지금까지 밝혀진 탈모요인에 대한 내용을 살펴보면, 모발 주기 조절과 관련된 모유두(dermal papilla)의 증식 억제 또는 기능 저하(Elliott K, et al., Differences in hair follicle dermal papilla volume are due to extracellular matrix volume and cell number: implications for the control of hair follicle size and androgen responses., J Invest Dermatol, 113, pp.873-877, 1999), 남성호르몬 작용에 의한 모발주기의 비정상화, 두피로의 혈류량 저하로 인한 모발주기의 비정상적 변화(Kaufman KD., Androgens and alopecia., Mol Cell Endocrinol, 198, pp.89-95, 2002), 항암제(Botchkarev VA., Molecular mechanisms of chemotherapy-induced hair loss., J Investig Dermatol Symp Proc, 8, pp.72-75, 2003), 정신적 스트레스, 물리적 자극 및 환경오염 등(Botchkarev VA., Stress and the hair follicle: Exploring the connections., Am J Pathol, 162, pp.709-712, 2003)이 거론되고 있다.Many studies have been conducted to treat hair loss in recent decades, but the cause of hair loss is still unknown. In view of the known hair loss factors, the suppression or reduction of the function of dermal papilla related to hair cycle regulation (Elliott K, et al. , Differences in hair follicle dermal papilla volume are due to extracellular matrix volume and cell number: implications for the control of hair follicle size and androgen responses., J Invest Dermatol , 113 , pp.873-877, 1999), aberrant hair cycles due to male hormone action, hair cycles due to decreased blood flow to the scalp Abnormal changes in (Kaufman KD., Androgens and alopecia., Mol) Cell Endocrinol , 198 , pp.89-95, 2002), anticancer agents (Botchkarev VA., Molecular mechanisms of chemotherapy-induced hair loss., J Investig Dermatol Symp Proc , 8 , pp.72-75, 2003), mental stress, physical Botchkarev VA., Stress and the hair follicle: Exploring the connections., Am J Pathol , 162 , pp. 709-712, 2003.

현재 모발성장을 촉진하는 약물로 미국식품의약국(Food and Drug Administration, FDA)의 승인을 받은 것으로서 미녹시딜(minoxidil)과 피나스테라이드(finasteride)가 잘 알려져 있다. 미녹시딜은 처음에 고혈압 치료를 위한 혈관확장제로 개발되었으나, 부작용으로 다모증이 보고되면서 발모제로 개발되었다. 미녹시딜의 발모효과에 대한 작용기전은 현재까지 명확히 밝혀지지 않았지만, 혈관확 장을 통한 영양공급 증가, 포타슘 채널 오프닝(potassium channel opening)효과 및 모유두세포(dermal papilla cells)의 세포사멸(apoptosis) 억제 효능 등이 모발성장을 유도하는 것으로 생각되고 있다(Han JH, et al., Effect of minoxodil on proliferation and apoptosis in dermal papilla cells of human hair follicle., J Dermatol Sci, 34, pp.91-98, 2004). 또한 머크(Merck)에서 개발한 피나스테라이드는 남성호르몬 대사에 작용하는 효소인 5α-환원효소(5α-reductase)의 활성을 억제시키는 물질로서 전립선 비대증 치료제로 개발되었으나, 모발의 성장을 촉진시킴이 알려지면서 발모제로 개발되었다(Kaufman KD, et al ., Finasteride, a Type 2 5alpha-reductase inhibitor, in the treatment of men with androgenetic alopecia., Expert Opin Investig Drugs, 8, pp.403-415, 1999). 최근 다양한 연구기관에서 육모 및 탈모 기전에 관여하는 많은 조절 인자들에 대한 연구가 활발히 진행되고 있으며, 특히 성장기, 퇴행기 및 휴지기의 모발주기에 관련된 여러 인자들과 그들의 수용체에 의한 신호전달에 의해 육모효과가 조절됨이 계속적으로 보고되고 있다. 예를 들어 EGF 및 EGFR(Botchkarev VA, et al., Molecular control of epithelial- mesenchymal interactions during hair follicle cycling., J Investig Dermatol Symp Proc, 8, pp.46-55, 2003), VEGF 및 VEGFR(Ozeki M, et al., In vivo promoted growth of mice hair follicles by the controlled release of growth factors., Biomaterials, 24, pp.2387-2394, 2003), HGF/SF 및 c-MET(Botchkarev VA, et al., Molecular control of epithelial-mesenchymal interactions during hair follicle cycling. J Investig Dermatol Symp Proc, 8, pp.46-55, 2003), FGF family 및 FGFR(Jang JH, Stimulation of human hair growth by the recombinant human KGF-2. Biotechnol . Lett, 27, pp.749-752, 2005), IGF 및 IGF-IR(Kamiya T, et al., Hair follicle elongation in organ culture of skin from newborn and adult mice., Dermatol Sci, 17, pp.54-60, 1998), TGF-β 및 TGF-βR(Hibino T, et al., Role of TGF-β2 in the human hair cycle., J. Dermatol . Sci, 35, pp.9-18, 2004) 등의 성장인자들이 모유두(dermal papilla)의 활성을 조절하여 모발주기에 영향을 미치는 것으로 보고되고 있다. 또한 돌출 부위(bulge region)에 있는 모낭 줄기세포의 증식 또는 분화에 Wnt 경로(pathway) 및 Bmp 신호(signaling)가 결정적으로 작용함이 밝혀지고 있다(Moore KA, et al., Stem cells and their niches. Science, 311, pp.1880-1885, 2006).Minoxidil and finasteride are well known as currently approved by the Food and Drug Administration (FDA) for promoting hair growth. Minoxidil was initially developed as a vasodilator for the treatment of hypertension, but it was developed as a hair restorer as hirsutism was reported as a side effect. The mechanism of action of minoxidil on the hair growth effect has not been clarified so far, but the effect of increased nutrient supply through vasodilation, potassium channel opening effect and apoptosis inhibition of dermal papilla cells Etc. are thought to induce hair growth (Han JH, et. al ., Effect of minoxodil on proliferation and apoptosis in dermal papilla cells of human hair follicle., J Dermatol Sci , 34 , pp. 91-98, 2004). Finasteride, developed by Merck, is a substance that inhibits the activity of 5α-reductase, an enzyme that acts on male hormone metabolism, and was developed as a treatment for prostatic hyperplasia, but it is known that it promotes hair growth. Developed as a hair restorer (Kaufman KD, et al . , Finasteride, a Type 2 5alpha-reductase inhibitor, in the treatment of men with androgenetic alopecia., Expert Opin Investig Drugs , 8 , pp. 403-415, 1999). Recently, various research institutes are actively researching a number of regulatory factors involved in hair growth and hair loss mechanisms, and in particular, hair growth effects due to signaling by various factors and their receptors related to the hair cycle of growth, degenerative and resting phases. Is constantly being reported. For example EGF and EGFR (Botchkarev VA, et al ., Molecular control of epithelial- mesenchymal interactions during hair follicle cycling., J Investig Dermatol Symp Proc , 8 , pp. 46-55, 2003), VEGF and VEGFR (Ozeki M, et al ., In vivo promoted growth of mice hair follicles by the controlled release of growth factors., Biomaterials , 24 , pp.2387-2394, 2003), HGF / SF and c-MET (Botchkarev VA, et. al ., Molecular control of epithelial-mesenchymal interactions during hair follicle cycling. J Investig Dermatol Symp Proc , 8 , pp. 46-55, 2003), FGF family and FGFR (Jang JH, Stimulation of human hair growth by the recombinant human KGF-2. Biotechnol . Lett , 27 , pp. 749-752, 2005), IGF and IGF-IR (Kamiya T, et al ., Hair follicle elongation in organ culture of skin from newborn and adult mice., Dermatol Sci , 17 , pp.54-60, 1998), TGF-β and TGF-βR (Hibino T, et al ., Role of TGF-β2 in the human hair cycle., J. Dermatol . Sci , 35 , pp.9-18, 2004) and others have been reported to affect the hair cycle by regulating the activity of dermal papilla. In addition, the Wnt pathway and Bmp signaling have been found to be crucial for the proliferation or differentiation of hair follicle stem cells in the bulb region (Moore KA, et. al ., Stem cells and their niches. Science , 311 , pp. 1880-1885, 2006).

모발의 성장은 여러 유전자와 성장인자 및 그 수용체, 전신적 호르몬의 작용 등으로 인한 복잡한 기전에 의해 일어난다. 특히 상피세포로 이루어진 모낭의 모기질 세포와 간엽세포로 구성된 모유두 세포가 모발의 형성 및 성장에 중추적인 요소로 작용한다. Jahoda(Jahoda CA, et al ., Induction of hair growth by implantation of cultured dermal papilla cells., Nature, 311, pp.560-562, 1984) 등에 의하면 쥐의 콧수염 모낭(rat vibrissa follicle)에서 모유두세포를 제거하였을 때, 모발의 성장이 일시적으로 중지하였다가 진피 근초로부터 세포가 이동하여 다시 모유두세포를 형성하고 모발의 성장이 다시 계속되었으며, 모낭의 아랫부분 1/3 이하를 제거하면 진피 근초로부터 모유두세포가 형성되고 외피 근초로부터 모기질세포가 형성되어 모발의 성장이 계속되나 모낭의 아랫부분 1/3 이상을 제거하면 모발의 성장의 중지되었다. 그러나 모낭의 아랫부분 1/3 이상을 제거한 후, 분리된 모유두세포를 이식하면 모발의 성장이 계속되는 사실로 미루어 모유두세포가 모발의 성장에 매우 중요한 역할을 하는 것으로 생각되고 있다. Hair growth is caused by a complex mechanism due to the action of several genes, growth factors and their receptors, and systemic hormones. In particular, hair follicle cells composed of epithelial cells and hair papilla cells composed of mesenchymal cells act as pivotal factors for hair formation and growth. Jahoda (Jahoda CA, et al . , Induction of hair growth by implantation of cultured dermal papilla cells., Nature , 311 , pp.560-562, 1984), etc., suggests that hair growth may be transient when hair papilla cells are removed from rat vibrissa follicles. The cells moved from the dermis roots to form hair papilla cells and hair growth continued again. If the lower third of the hair follicles were removed, the dermal papilla cells were formed from the dermis roots and the matrix cells from the outer root roots. Was formed and hair growth continued, but when the lower third of the hair follicles were removed, hair growth stopped. However, after removing more than one-third of the lower part of the hair follicles and transplanting the isolated dermal papilla cells, the growth of the hair continues, and it is thought that the dermal papilla cells play an important role in the hair growth.

섬오갈피나무(Acanthopanax koreanum Nakai)는 두릅나무과(araliaceae)에 속하는 낙엽관목으로 한국 특산 식물이다. 우리나라에 자생하고 있는 오갈피속 식물로는 섬오갈피나무를 비롯하여 10종 3품종이 있다(Han DR, et al., Studies on morphological and chemotaxonomy and seco-triterpene glycoside component of korean Acanthopanax spp., Bull . D.. S. Pharm . Sci . Inst, 11, pp.1-66, 1994). 특히 섬오갈피나무는 해발 500 m 아래의 제주도 전역에 분포하고 있으며, 최근에는 천안 등 육지에서도 쉽게 재배되고 있고 실생 또는 삽목 번식이 쉬운 식물이다(박호기, 가시오갈피의 삽목 번식방법, 약용작물학회지, 2, pp.133-139, 1994). 현재까지 섬오갈피나무의 뿌리와 줄기의 성분으로는 리그난(lignan) 배당체인 시린가레시놀 디글리코사이드(syringaresinol diglycoside)(Kim YH, et al., Studies on the constituents of Acanthopanax koreanum Nakai(1)., Kor . J. Pharmacogn, 16, pp.151-154, 1985), 아칸토사이드 D(acanthoside D), 시린고사이드(syringoside)(Hahn DR, et al., A study on the chemical constituents of Acanthopanax koreanum and its pharmacobiological activities., Yakhak Hoeji, 29, pp.357-361, 1985), 엘레우테로사이드(eleutheroside) B 및 E(Chung BS, et al., Studies on the constituents of Acanthopanax koreanum Nakai., Kor . J. Pharmacogn, 17, pp.62-66, 1986), 팔카린돌(falcarindol), 메틸 n-헥사코사노에이 트(methyl n-hexacosanoate), 코니페린(coniferin)(Kim YH, et al., Studies on the chemical constituents of Acanthopanax koreanum , Arch . Pharm . Res, 11, pp.159-162, 1988), 피마라딘 디터펜(pimaradine diterpene)(Kim YH, et al., Pimaradine diterpenes from Acanthopanax koreanum . J. Nat . Prod, 51, pp.1080-1082, 1988) 및 수모가사이드(sumogaside)(Kim YH, et al., Diterpene glycoside form Acanthopanax koreanum., Kor . J. Pharmacogn, 21, pp.49-51, 1990), 루펜 글리코사이드(lupane glycosides)(Choi HS, et al., Lupane glycosides from the leaves of Acanthopanax koreanum., Chem . Pharm . Bull, 56, pp.1613-1616, 2008) 등이 함유되어 있는 것으로 알려져 있다. 섬오갈피나무는 강장, 류마티스, 당뇨, 간질환에 효능이 있는 것으로 알려져 있으나(Perry LM, et al., Medicinal Plants of East and Southeast Asia. MIT Press, Cambrige, p.41, 1980), 섬오갈피나무 추출물의 발모 및 육모 효능에 대한 연구 및 보고는 거의 없는 실정이다. Acanthopanax koreanum Nakai) is a deciduous shrub belonging to the araliaceae family and is a Korean specialty plant. There are three varieties of 10 kinds of plants in Korea, including the island of Ogalpi trees (Han DR, et. al ., Studies on morphological and chemotaxonomy and seco-triterpene glycoside component of korean Acanthopanax spp., Bull . D .. S. Pharm . Sci . Inst , 11 , pp. 1-66, 1994). In particular, island oakpi trees are distributed all over Jeju Island below 500 m above sea level. Recently, they are easily cultivated on land such as Cheonan and are easy to reproduce in real life or in cuttings (Park Ho-ki, cutting method of prickly ginseng, Journal of Medicinal Crop Science, 2 , pp. 133-139, 1994). To date, the roots and stems of the island oak tree are lignan glycosides, siringaresinol diglycoside (Kim YH, et. al ., Studies on the constituents of Acanthopanax koreanum Nakai (1)., Kor . J. Pharmacogn , 16 , pp. 151-154, 1985), acanthoside D, syringoside (Hahn DR, et. al ., A study on the chemical constituents of Acanthopanax koreanum and its pharmacobiological activities., Yakhak Hoeji , 29 , pp.357-361, 1985), eleutheroside B and E (Chung BS, et al ., Studies on the constituents of Acanthopanax koreanum Nakai., Kor . J. Pharmacogn , 17 , pp. 62-66, 1986), falcarindol, methyl n-hexacosanoate, coniferin (Kim YH, et. al ., Studies on the chemical constituents of Acanthopanax koreanum , Arch . Pharm . Res , 11 , pp. 159-162, 1988), pimaradine diterpene (Kim YH, et. al ., Pimaradine diterpenes from A canthopanax koreanum . J. Nat . Prod , 51 , pp. 1080-1082, 1988) and sumogaside (Kim YH, et. al ., Diterpene glycoside form Acanthopanax koreanum ., Kor . J. Pharmacogn , 21 , pp. 49-51, 1990), lupane glycosides (Choi HS, et. al ., Lupane glycosides from the leaves of Acanthopanax koreanum , Chem . Pharm . Bull , 56 , pp. 1613-1616, 2008). Island oak bark is known to be effective in tonic, rheumatism, diabetes and liver disease (Perry LM, et. al ., Medicinal Plants of East and Southeast Asia. MIT Press, Cambrige, p.41, 1980), there are few studies and reports on the hair growth and hair growth efficacy of S. aureus extract.

이에 본 발명자들은 섬오갈피나무 추출물 또는 이로부터 분리한 신규화합물 acankoreoside J에 의한 탈모 방지 및 발모 개선 효과에 대해 지속적으로 연구한 결과, 랫트의 콧수염 모낭(vibrissa follicles) 성장 효과 및 모발의 성장에 중요한 역할을 하는 모유두세포(Dermal papilla cell)의 성장증식 효과를 확인하여 본 발명을 완성하게 되었다.Therefore, the present inventors have continuously studied the hair loss prevention and hair growth improvement effect by the extract of S. agakorpi extract or a novel compound isolated therefrom, which plays an important role in the growth effect of vibrissa follicles and hair growth of rats. By confirming the growth proliferation effect of the dermal papilla cells (Dermal papilla cells) to complete the present invention.

상기 목적을 수행하기 위하여, 본 발명은 섬오갈피나무 추출물 또는 이로부 터 분리한 하기 구조식(Ⅰ)의 신규화합물 acankoreoside J를 유효성분으로 함유하는 탈모 방지 및 발모 개선용 피부외용 약학 조성물을 제공한다:In order to achieve the above object, the present invention provides a skin external pharmaceutical composition for preventing hair loss and improving hair growth, containing an acankoreoside J of the following structural formula (I) isolated from an extract of S. aureus.

Figure 112009025848189-pat00001
(Ⅰ)
Figure 112009025848189-pat00001
(Ⅰ)

또한, 본 발명은 섬오갈피나무 추출물 또는 이로부터 분리한 신규화합물 acankoreoside J를 유효성분으로 함유하는 탈모 방지 및 발모 개선용 화장료 조성물을 제공한다.In addition, the present invention provides a cosmetic composition for preventing hair loss and improving hair growth, which contains an extract of S. augkorpi tree or a novel compound isolated from the acankoreoside J as an active ingredient.

본원에서 정의되는 상기 추출물은 섬오갈피나무의 줄기, 뿌리 또는 잎, 바람직하게는 줄기 또는 잎으로부터 수득됨을 특징으로 한다. The extract as defined herein is characterized in that it is obtained from the stem, root or leaf, preferably the stem or leaf of the island of the islands.

본원에서 정의되는 상기 추출물은 정제수를 포함한 물, 주정, C1 내지 C4의 저급 알콜 또는 이들의 혼합용매, 바람직하게는 물, 주정, 메탄올 또는 이들의 혼 합용매에 가용한 추출물을 포함한다.The extract as defined herein includes extracts available in water, spirits, C 1 to C 4 lower alcohols or mixed solvents thereof, preferably water, alcohols, methanol or mixed solvents thereof, including purified water.

상기 피부외용 약학조성물은 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 또는 카타플라스마제 제형을 포함한다.The external skin pharmaceutical composition includes a cream, gel, patch, spray, ointment, warning, lotion, linen, pasta or cataplasma formulation.

또한, 상기 화장료 조성물은 헤어토닉, 헤어컨디셔너, 헤어에센스, 헤어로션, 헤어영양로션, 헤어샴푸, 헤어린스, 헤어트리트먼트, 헤어크림, 헤어영양크림, 헤어모이스처크림, 헤어맛사지크림, 헤어왁스, 헤어 에어로졸, 헤어팩, 헤어영양팩, 헤어비누, 헤어클렌징폼, 머릿기름, 모발건조제, 모발보존처리제, 모발염색제, 모발용 웨이브제, 모발탈색제, 헤어겔, 헤어글레이즈, 헤어드레싱어, 헤어래커, 헤어모이스처라이저, 헤어무스 또는 헤어스프레이의 제형을 포함한다.In addition, the cosmetic composition is a hair tonic, hair conditioner, hair essence, hair lotion, hair nutrition lotion, hair shampoo, hair rinse, hair treatment, hair cream, hair nutrition cream, hair moisturizer cream, hair massage cream, hair wax, Hair aerosol, hair pack, hair nutrition pack, hair soap, hair cleansing foam, hair oil, hair drier, hair preservative, hair dye, hair wave agent, hair bleach, hair gel, hair glaze, hair dresser, hair lacquer, hair moisturizer Formulations of risers, hair mousses or hairsprays.

이하, 본 발명의 추출물 및 신규화합물을 수득하는 방법을 상세히 설명한다.Hereinafter, the method of obtaining the extract and the novel compound of the present invention will be described in detail.

본 발명의 추출물은 섬오갈피나무의 줄기, 뿌리 및 잎 각각을 자연건조하여 절편한 후, 건조된 시료 중량의 약 0.01 내지 10배(v/w), 바람직하게는 약 0.1 내지 3배(v/w) 분량의 정제수를 포함한 물, 주정, C1 내지 C4의 저급 알콜 또는 이들의 혼합용매, 바람직하게는 물, 주정 또는 이들의 혼합용매에 넣고, 90 ℃이상의 온도에서 약 0.5 내지 24시간, 바람직하게는 1 내지 12시간동안 냉침추출, 열수추출, 초음파 추출, 환류냉각 추출, 가열추출 등, 바람직하게는 열수추출법으로 1 내지 5회, 바람직하게는 2 내지 3회 반복하여 추출하고 여과한 후, 감압농축 및 동결건조하는 제조공정을 통하여 본 발명의 추출물을 수득할 수 있다.The extract of the present invention, after sectioning each of the stems, roots and leaves of the island of Dalpipi by air drying, is about 0.01 to 10 times (v / w), preferably about 0.1 to 3 times (v / w) of the dried sample weight w) water, alcohol, lower alcohols of C 1 to C 4 or a mixed solvent thereof, preferably water, alcohol or a mixed solvent thereof, containing a quantity of purified water, and about 0.5 to 24 hours at a temperature of 90 ° C. or higher, Preferably 1 to 12 hours cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, heating extraction, and the like, preferably by hot water extraction method is repeated 1 to 5 times, preferably 2 to 3 times and extracted and filtered The extract of the present invention can be obtained through a manufacturing process of concentration under reduced pressure and lyophilization.

또한, 섬오갈피나무의 잎을 건조하여 세절한 후, 건조된 시료 중량의 약 0.5 내지 50배(v/w) 분량의 메탄올을 가하여 0 ℃ 내지 100 ℃, 바람직하게는 30 ℃ 내지 50 ℃에서 1 내지 10시간동안 냉침추출, 열수추출, 초음파 추출, 환류냉각 추출, 가열추출 등, 바람직하게는 열수추출법으로 1 내지 5회, 바람직하게는 2 내지 3회 반복하여 추출하고 여과한 후, 감압농축하여 메탄올엑스를 수득하는 제 1단계; 상기 메탄올엑스에 증류수 및 헥산(Hexane)을 가하고 진탕하여 헥산층과 수층으로 분획한 후, 수층에 에틸아세테이트를 가하고 진탕하여 에틸아세테이트층과 수층으로 나눈 다음, 에틸아세테이트층과 수층을 각각 감압농축하여 에틸아세테이트 분획물 및 수가용성 분획물을 수득하는 제 2단계; 상기 수가용성 분획물을 Diaion HP-20 컬럼에 로딩한 후, 물과 메탄올을 이동상으로 하여 용매 구배(100% 물, 90% 메탄올, 75% 메탄올, 50% 메탄올, 20% 메탄올, 100% 메탄올)로 용출하여 수득한 50% 메탄올 분획을 실리카겔과 YMC RP-18 컬럼 크로마토그래피를 반복수행하는 제 3단계의 제조공정을 통하여 본 발명의 화합물을 분리정제할 수 있다. In addition, after drying and cutting off the leaves of the leaves of S. aureus, about 0.5 to 50 times (v / w) of methanol is added to the dried sample weight to 1 to 0 ° C to 100 ° C, preferably 30 ° C to 50 ° C. Cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, heating extraction for 10 to 10 hours, preferably 1 to 5 times, preferably 2 to 3 times repeated extraction and filtration by hot water extraction method, concentrated under reduced pressure A first step of obtaining methanol extract; Distilled water and hexane (Hexane) was added to the methanol extract, and the mixture was shaken and fractionated into a hexane layer and an aqueous layer. Then, ethyl acetate was added to the aqueous layer, shaken, divided into an ethyl acetate layer and an aqueous layer, and the ethyl acetate layer and the aqueous layer were concentrated under reduced pressure, respectively. A second step of obtaining an ethyl acetate fraction and a water soluble fraction; The water soluble fraction was loaded onto a Diaion HP-20 column, followed by a solvent gradient (100% water, 90% methanol, 75% methanol, 50% methanol, 20% methanol, 100% methanol) with water and methanol as mobile phases. The compound of the present invention can be separated and purified through the third step of preparing 50% methanol fraction obtained by eluting with silica gel and YMC RP-18 column chromatography.

본 발명의 탈모 방지 및 발모 개선용 조성물은, 조성물 총 중량에 대하여 상기 추출물 또는 화합물을 0.1 내지 50% 중량으로 포함한다.The composition for preventing hair loss and improving hair growth of the present invention comprises 0.1 to 50% by weight of the extract or compound based on the total weight of the composition.

그러나 상기와 같은 조성은 반드시 이에 한정되는 것은 아니고, 환자의 상태 및 진행 정도에 따라 변할 수 있다.However, the composition is not limited thereto, and may vary depending on the condition and progress of the patient.

본 발명의 섬오갈피나무 추출물 또는 이로부터 분리한 신규화합물을 유효성분으로 함유하는 피부외용 약학조성물은 탈모 방지 및 발모 개선용 피부외용제로서 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 또는 카 타플라스마제의 피부 외용제 형태의 약학조성물로 제조하여 사용할 수 있으나, 이에 한정하는 것은 아니다. The skin external pharmaceutical composition containing an extract of the island of the present invention or a novel compound separated therefrom as an active ingredient is a skin external preparation for preventing hair loss and improving hair growth, such as creams, gels, patches, sprays, ointments, warning agents, lotions, It may be prepared and used as a pharmaceutical composition in the form of an external preparation for skin, such as linen, pasta, or cataplasma, but is not limited thereto.

본 발명의 추출물 또는 화합물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 본 발명의 추출물 또는 화합물은 1일 0.0001 내지 100 ㎎/㎏으로, 바람직하게는 0.001 내지 10 ㎎/㎏으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. Preferred dosages of the extracts or compounds of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the extract or compound of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably at 0.001 to 10 mg / kg. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.

또한, 본 발명의 섬오갈피나무 추출물 또는 이로부터 분리한 신규화합물을 유효성분으로 함유하는 탈모 방지 및 발모를 활성화시키는 효과를 갖는 모발화장품에 다양하게 이용될 수 있다. 본 조성물을 첨가할 수 있는 제품으로는, 예를 들어, 헤어토닉, 헤어컨디셔너, 헤어에센스, 헤어로션, 헤어영양로션, 헤어샴푸, 헤어린스, 헤어트리트먼트, 헤어크림, 헤어영양크림, 헤어모이스처크림, 헤어맛사지크림, 헤어왁스, 헤어 에어로졸, 헤어팩, 헤어영양팩, 헤어비누, 헤어클렌징폼, 머릿기름, 모발건조제, 모발보존처리제, 모발염색제, 모발용 웨이브제, 모발탈색제, 헤어겔, 헤어글레이즈, 헤어드레싱어, 헤어래커, 헤어모이스처라이저, 헤어무스 또는 헤어스프레이 등과 같은 화장품류 등이 있다.In addition, it may be variously used in hair cosmetics having the effect of preventing hair loss and activating hair growth, containing an extract of the island of the island of the present invention or a novel compound separated therefrom as an active ingredient. Examples of products to which the composition can be added include, for example, hair tonics, hair conditioners, hair essences, hair lotions, hair nutrition lotions, hair shampoos, hair rinses, hair treatments, hair creams, hair nutrition creams, hair moisturizers. Cream, hair massage cream, hair wax, hair aerosol, hair pack, hair nutrition pack, hair soap, hair cleansing foam, hair oil, hair dryer, hair preservative, hair colorant, hair wave agent, hair bleach, hair gel, hair glaze, Cosmetics such as hair dressers, hair lacquers, hair moisturizers, hair mousses or hair sprays and the like.

본 발명의 화장료는 수용성 비타민, 유용성 비타민, 고분자 펩티드, 고분자 다당, 스핑고 지질 및 해초 엑기스로 이루어진 군에서 선택된 조성물을 포함한다.Cosmetics of the present invention comprises a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids and seaweed extract.

수용성 비타민으로서는 화장품에 배합 가능한 것이라면 어떠한 것이라도 되 지만, 바람직하게는 비타민 B1, 비타민 B2, 비타민 B6, 피리독신, 염산피리독신, 비타민 B12, 판토텐산, 니코틴산, 니코틴산아미드, 엽산, 비타민 C, 비타민 H 등을 들 수 있으며, 그들의 염(티아민염산염, 아스코르빈산나트륨염 등)이나 유도체(아스코르빈산-2-인산나트륨염, 아스코르빈산-2-인산마그네슘염 등)도 본 발명에서 사용할 수 있는 수용성 비타민에 포함된다. 수용성 비타민은 미생물 변환법, 미생물의 배양물로부터의 정제법, 효소법 또는 화학 합성법 등의 통상의 방법에 의해 수득할 수 있다.The water-soluble vitamin may be any compound that can be incorporated into cosmetics, but preferably vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, vitamin H, and the like. And salts thereof (thiamine hydrochloride, sodium ascorbate salt, etc.) and derivatives (ascorbic acid-2-sodium phosphate salt, ascorbic acid-2-magnesium phosphate salt, etc.) can also be used in the present invention. Included in The water-soluble vitamins can be obtained by conventional methods such as microbial transformation, purification from microorganism culture, enzyme or chemical synthesis.

유용성 비타민으로서는 화장품에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 비타민 A, 카로틴, 비타민 D2, 비타민 D3, 비타민 E(d1-알파 토코페롤, d-알파 토코페롤, d-알파 토코페롤) 등을 들 수 있으며, 그들의 유도체(팔미틴산아스코르빈, 스테아르산아스코르빈, 디팔미틴산아스코르빈, 아세트산 dl-알파 토코페롤, 니코틴산 dl-알파 토코페롤비타민 E, DL-판토테닐알코올, D-판토테닐알코올, 판토테닐에틸에테르 등) 등도 본 발명에서 사용되는 유용성 비타민에 포함된다. 유용성 비타민은 미생물 변환법, 미생물의 배양물로부터의 정제법, 효소 또는 화학 합성법 등의 통상의 방법에 의해 취득할 수 있다.The oil-soluble vitamin may be any compound that can be formulated into cosmetics, but preferably vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol), and the like. And derivatives thereof (ascorbic palmitate, ascorbic stearate, ascorbic acid dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherolvitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantotenylethyl Ethers, etc.) are also included in the oil-soluble vitamins used in the present invention. Oil-soluble vitamins can be obtained by conventional methods such as microbial transformation, purification of microorganism culture, enzyme or chemical synthesis.

고분자 펩티드로서는 화장품에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 콜라겐, 가수 분해 콜라겐, 젤라틴, 엘라스틴, 가수 분해 엘라스틴, 케라틴 등을 들 수 있다. 고분자 펩티드는 미생물의 배양액으로부터의 정제법, 효소법 또는 화학 합성법 등의 통상의 방법에 의해 정제 취득할 수 있으며, 또는 통상 돼지나 소 등의 진피, 누에의 견섬유 등의 천연물로부터 정제하여 사용할 수 있다.The polymeric peptide may be any compound as long as it can be compounded in cosmetics, and examples thereof include collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, and keratin. Polymeric peptides can be purified and obtained by conventional methods such as purification from microbial cultures, enzymatic methods or chemical synthesis methods, or can be purified and used from natural products such as dermis and pig silk such as pigs and cattle.

고분자 다당으로서는 화장품에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 히드록시에틸셀룰로오스, 크산탄검, 히알루론산나트륨, 콘드로이틴 황산 또는 그 염(나트륨염 등) 등을 들 수 있다. 예를 들어, 콘드로이틴 황산 또는 그 염 등은 통상 포유동물이나 어류로부터 정제하여 사용할 수 있다.The polymer polysaccharide may be any compound as long as it can be incorporated into cosmetics. Preferably, hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate or a salt thereof (sodium salt, etc.) may be mentioned. For example, chondroitin sulfate or its salt, etc. can be normally purified from a mammal or fish.

스핑고 지질로서는 화장품에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 세라미드, 피토스핑고신, 스핑고당지질 등을 들 수 있다. 스핑고 지질은 통상 포유류, 어류, 패류, 효모 또는 식물 등으로부터 통상의 방법에 의해 정제하거나 화학 합성법에 의해 취득할 수 있다.The sphingolipid may be any compound as long as it can be blended into cosmetics. Preferably, ceramide, phytosphingosine, sphingosaccharide lipid, etc. may be mentioned. Sphingo lipids can usually be purified from mammals, fish, shellfish, yeasts or plants by conventional methods or obtained by chemical synthesis.

해초 엑기스로는 화장품에 배합 가능한 것이라면 어떠한 것이라도 되지만, 바람직하게는 갈조 엑기스, 홍조 엑기스, 녹조 엑기스 등을 들 수 있으며, 또, 이들의 해초 엑기스로부터 정제된 칼라기난, 아르긴산, 아르긴산나트륨, 아르긴산칼륨 등도 본 발명에서 사용되는 해초 엑기스에 포함된다. 해초 엑기스는 해초로부터 통상의 방법에 의해 정제하여 취득할 수 있다.The seaweed extract may be any compound as long as it can be blended into cosmetics. Preferably, the seaweed extract may include brown algae extract, red algae extract, green algae extract, and the like. Also, calginine, arginic acid, sodium arginate, Potassium arginate and the like are also included in the seaweed extract used in the present invention. Seaweed extract can be obtained by purification from seaweed by conventional methods.

본 발명의 화장료에는 상기 필수 성분과 더불어 필요에 따라 통상 화장료에 배합되는 다른 성분을 배합해도 된다.The cosmetic of the present invention may be blended with other essential ingredients, if necessary, in combination with the essential ingredients.

이외에 첨가해도 되는 배합 성분으로서는 유지 성분, 보습제, 에몰리엔트제, 계면 활성제, 유기 및 무기 안료, 유기 분체, 자외선 흡수제, 방부제, 살균제, 산화 방지제, 식물 추출물, pH 조정제, 알콜, 색소, 향료, 혈행 촉진제, 냉감제, 제한(制汗)제, 정제수 등을 들 수 있다.Other components that may be added include fats and oils, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavorings, Blood circulation accelerators, cooling agents, restriction agents, purified water and the like.

유지 성분으로서는 에스테르계 유지, 탄화수소계 유지, 실리콘계 유지, 불소계 유지, 동물 유지, 식물 유지 등을 들 수 있다.Examples of the fat or oil component include ester fats, hydrocarbon fats, silicone fats, fluorine fats, animal fats, and vegetable fats and oils.

에스테르계 유지로서는 트리2-에틸헥산산글리세릴, 2-에틸헥산산세틸, 미리스틴산이소프로필, 미리스틴산부틸, 팔미틴산이소프로필, 스테아르산에틸, 팔미틴산옥틸, 이소스테아르산이소세틸, 스테아르산부틸, 리놀레산에틸, 리놀레산이소프로필, 올레인산에틸, 미리스틴산이소세틸, 미리스틴산이소스테아릴, 팔미틴산이소스테아릴, 미리스틴산옥틸도데실, 이소스테아르산이소세틸, 세바신산디에틸, 아디핀산디이소프로필, 네오펜탄산이소알킬, 트리(카프릴, 카프린산)글리세릴, 트리2-에틸헥산산트리메틸롤프로판, 트리이소스테아르산트리메틸롤프로판, 테트라2-에틸헥산산펜타엘리슬리톨, 카프릴산세틸, 라우린산데실, 라우린산헥실, 미리스틴산데실, 미리스틴산미리스틸, 미리스틴산세틸, 스테아르산스테아릴, 올레인산데실, 리시노올레인산세틸, 라우린산이소스테아릴, 미리스틴산이소트리데실, 팔미틴산이소세틸, 스테아르산옥틸, 스테아르산이소세틸, 올레인산이소데실, 올레인산옥틸도데실, 리놀레산옥틸도데실, 이소스테아르산이소프로필, 2-에틸헥산산세토스테아릴, 2-에틸헥산산스테아릴, 이소스테아르산헥실, 디옥탄산에틸렌글리콜, 디올레인산에틸렌글리콜, 디카프린산프로필렌글리콜, 디(카프릴,카프린산)프로필렌글리콜, 디카프릴산프로필렌글리콜, 디카프린산네오펜틸글리콜, 디옥탄산네오펜틸글리콜, 트리카프릴산글리세릴, 트리운데실산글리세릴, 트리이소팔미틴산글리세릴, 트리이소스테아르산글리세릴, 네오펜탄산옥틸도데실, 옥탄산이소스테아릴, 이소노난산옥틸, 네오데칸산헥실데실, 네오데칸산옥틸도데실, 이소스테아르산이소세틸, 이소스테아 르산이소스테아릴, 이소스테아르산옥틸데실, 폴리글리세린올레인산에스테르, 폴리글리세린이소스테아르산에스테르, 시트르산트리이소세틸, 시트르산트리이소알킬, 시트르산트리이소옥틸, 락트산라우릴, 락트산미리스틸, 락트산세틸, 락트산옥틸데실, 시트르산트리에틸, 시트르산아세틸트리에틸, 시트르산아세틸트리부틸, 시트르산트리옥틸, 말산디이소스테아릴, 히드록시스테아르산 2-에틸헥실, 숙신산디2-에틸헥실, 아디핀산디이소부틸, 세바신산디이소프로필, 세바신산디옥틸, 스테아르산콜레스테릴, 이소스테아르산콜레스테릴, 히드록시스테아르산콜레스테릴, 올레인산콜레스테릴, 올레인산디히드로콜레스테릴, 이소스테아르산피트스테릴, 올레인산피트스테릴, 12-스테알로일히드록시스테아르산이소세틸, 12-스테알로일히드록시스테아르산스테아릴, 12-스테알로일히드록시스테아르산이소스테아릴 등의 에스테르계 등을 들 수 있다.As ester fats and oils, glyceryl tri2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl mystinate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, and stearic acid Butyl, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl acid isocetyl, isostyl acid isostearyl, isostaryl palmitate, octylate acid octyldodecyl, isostearic acid isetyl, diethyl sebacate, adipine Acid isopropyl, isoalkyl neopentane, tri (capryl, capric acid) glyceryl, trimethyl ethyl trimethylol propane, triisostearic acid trimethylol propane, tetra 2-ethylhexanoic penta erythritol Cetyl caprylate, lauric acid decyl, hexyl laurate, decyl myristin, myristin acid myristyl, myritic acid cetyl, stearyl stearate, decyl oleate, rininooleic acid , Isostearyl laurate, isotridecyl myristin, isocetyl palmitate, octyl stearate, isocetyl stearate, isodecate oleate, octylate decyl oleate, octyl dodecyl linoleate, isopropyl isopropyl acid, 2 -Cetostearyl ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicapric acid, propylene glycol dicacapate, capric acid Propylene glycol, dicapric acid neopentyl glycol, dioctanoate neopentyl glycol, tricaprylic acid glyceryl, triundecyl glyceryl, triisopalmitinate glyceryl, triisostearate glyceryl, neopentane dodecyl Isostearyl octanoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, Sothete octylate, polyglycerol oleate, polyglycerine isostearate, triisocetyl citrate, triisoalkyl citrate, triisoctyl citrate, lauryl lactate, myritic lactate, octyl lactate, octyl lactate, tricitric acid Ethyl, acetyl triethyl citrate, acetyl tributyl citrate, trioctyl citrate, diisostearyl malic acid, 2-ethylhexyl hydroxystearate, di2-ethylhexyl succinate, diisobutyl adipicate, diisopropyl sebacinate, Dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, physteryl isostearate, phytic oleate, 12-Steloylhydroxystearate isocetyl, 12-Steloylhydroxystearate stearyl, 12-steal One hydroxy stearic acid and the like esters such as cetearyl source.

탄화 수소계 유지로서는 스쿠알렌, 유동 파라핀, 알파-올레핀올리고머, 이소파라핀, 세레신, 파라핀, 유동 이소파라핀, 폴리부덴, 마이크로크리스탈린왁스, 와셀린 등의 탄화 수소계 유지 등을 들 수 있다.Hydrocarbon-based fats and oils, such as squalene, a liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, a liquid isoparaffin, polybutene, microcrystal wax, and a vaseline, etc. are mentioned as a hydrocarbon-type fats and oils.

실리콘계 유지로서는 폴리메틸실리콘, 메틸페닐실리콘, 메틸시클로폴리실록산, 옥타메틸폴리실록산, 데카메틸폴리실록산, 도데카메틸시클로실록산, 디메틸실록산ㆍ메틸세틸옥시실록산 공중합체, 디메틸실록산ㆍ메틸스테알록시실록산 공중합체, 알킬 변성 실리콘유, 아미노 변성 실리콘유 등을 들 수 있다.Examples of the silicone-based oils and fats include polymethylsilicone, methylphenylsilicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane, methylcetyloxysiloxane copolymer, dimethylsiloxane and methylsteoxysiloxane copolymer, and alkyl. Modified silicone oil, amino modified silicone oil and the like.

불소계 유지로서는 퍼플루오로폴리에테르 등을 들 수 있다.Examples of the fluorine-based oil include perfluoropolyether and the like.

동물 또는 식물 유지로서는 아보카도유, 아르몬드유, 올리브유, 참깨유, 쌀 겨유, 새플라워유, 대두유, 옥수수유, 유채유, 행인(杏仁)유, 팜핵유, 팜유, 피마자유, 해바라기유, 포도종자유, 면실유, 야자유, 쿠쿠이너트유, 소맥배아유, 쌀 배아유, 시아버터, 월견초유, 마커데이미아너트유, 메도홈유, 난황유, 우지(牛脂), 마유, 밍크유, 오렌지라피유, 호호바유, 캔데리러왁스, 카르나바왁스, 액상 라놀린, 경화피마자유 등의 동물 또는 식물 유지를 들 수 있다.As animal or vegetable fats and oils, avocado oil, almond oil, olive oil, sesame oil, rice bran oil, soybean oil, soybean oil, corn oil, rapeseed oil, almond oil, palm kernel oil, palm oil, castor oil, sunflower oil, grape seed oil , Cottonseed oil, Palm oil, Cucumber nut oil, Wheat germ oil, Rice germ oil, Shea butter, Walnut colostrum oil, Marker demia nut oil, Meadow home oil, Egg yolk oil, Uji, Horse oil, Mink oil, Orange rape oil, Jojoba oil And animal or plant fats and oils such as candeler wax, carnava wax, liquid lanolin and hardened castor oil.

보습제로서는 수용성 저분자 보습제, 지용성 분자 보습제, 수용성 고분자, 지용성 고분자 등을 들 수 있다.Examples of the moisturizing agent include a water-soluble low molecular moisturizer, a fat-soluble molecular moisturizer, a water-soluble polymer, and a fat-soluble polymer.

수용성 저분자 보습제로서는 세린, 글루타민, 솔비톨, 만니톨, 피롤리돈-카르복실산나트륨, 글리세린, 프로필렌글리콜, 1,3-부틸렌글리콜, 에틸렌글리콜, 폴리에틸렌글리콜B(중합도 n = 2 이상), 폴리프로필렌글리콜(중합도 n = 2 이상), 폴리글리세린B(중합도 n = 2 이상), 락트산, 락트산염 등을 들 수 있다.Water-soluble low molecular humectants include serine, glutamine, sorbitol, mannitol, pyrrolidone-sodium carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B (polymerization degree n = 2 or more), polypropylene Glycol (polymerization degree n = 2 or more), polyglycerol B (polymerization degree n = 2 or more), lactic acid, lactic acid salt, etc. are mentioned.

지용성 저분자 보습제로서는 콜레스테롤, 콜레스테롤에스테르 등을 들 수 있다.Examples of the fat-soluble low molecular humectants include cholesterol and cholesterol esters.

수용성 고분자로서는 카르복시비닐폴리머, 폴리아스파라긴산염, 트라가칸트, 크산탄검, 메틸셀룰로오스, 히드록시메틸셀룰로오스, 히드록시에틸셀룰로오스, 히드록시프로필셀룰로오스, 카르복시메틸셀룰로오스, 수용성 키틴, 키토산, 덱스트린 등을 들 수 있다.Examples of the water-soluble polymer include carboxyvinyl polymer, polyasparaginate, tragacanth, xanthan gum, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, water soluble chitin, chitosan, and dextrin. Can be.

지용성 고분자로서는 폴리비닐피롤리돈ㆍ에이코센 공중합체, 폴리비닐피롤리돈ㆍ헥사데센 공중합체, 니트로셀룰로오스, 덱스트린지방산에스테르, 고분자 실리콘 등을 들 수 있다.Examples of the fat-soluble polymers include polyvinylpyrrolidone-eicosene copolymers, polyvinylpyrrolidone-hexadecene copolymers, nitrocellulose, dextrin fatty acid esters, polymer silicones, and the like.

에몰리엔트제로서는 장쇄아실글루타민산콜레스테릴에스테르, 히드록시스테아르산콜레스테릴, 12-히드록시스테아르산, 스테아르산, 로진산, 라놀린지방산콜레스테릴에스테르 등을 들 수 있다.Examples of the emollient include long-chain acyl glutamic acid cholesteryl esters, hydroxy stearic acid cholesterol, 12-hydroxystearic acid, stearic acid, rosin acid, lanolin fatty acid cholesteryl esters, and the like.

계면 활성제로서는 비이온성 계면 활성제, 음이온성 계면 활성제, 양이온성 계면 활성제, 양성 계면 활성제 등을 들 수 있다.As surfactant, nonionic surfactant, anionic surfactant, cationic surfactant, amphoteric surfactant, etc. are mentioned.

비이온성 계면 활성제로서는 자기 유화형 모노스테아르산글리세린, 프로필렌글리콜지방산에스테르, 글리세린지방산에스테르, 폴리글리세린지방산에스테르, 솔비탄지방산에스테르, POE(폴리옥시에틸렌) 솔비탄지방산에스테르, POE 솔비트지방산에스테르, POE 글리세린지방산에스테르, POE 알킬에테르, POE 지방산에스테르, POE 경화피마자유, POE 피마자유, POEㆍPOP(폴리옥시에틸렌ㆍ폴리옥시프로필렌) 공중합체, POEㆍPOP 알킬에테르, 폴리에테르변성실리콘, 라우린산알카놀아미드, 알킬아민옥시드, 수소첨가대두인지질 등을 들 수 있다.As nonionic surfactant, self-emulsifying glycerin monostearate, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerol fatty acid ester, sorbitan fatty acid ester, POE (polyoxyethylene) sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE Glycerin Fatty Acid Ester, POE Alkyl Ether, POE Fatty Acid Ester, POE Cured Castor Oil, POE Castor Oil, POE / POP (Polyoxyethylene / Polyoxypropylene) Copolymer, POE / POP Alkyl Ether, Polyether Modified Silicone, Laurin Acid Alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, etc. are mentioned.

음이온성 계면 활성제로서는 지방산비누, 알파-아실술폰산염, 알킬술폰산염, 알킬알릴술폰산염, 알킬나프탈렌술폰산염, 알킬황산염, POE 알킬에테르황산염, 알킬아미드황산염, 알킬인산염, POE 알킬인삼염, 알킬아미드인산염, 알킬로일알킬타우린염, N-아실아미노산염, POE 알킬에테르카르복실산염, 알킬술포숙신산염, 알킬술포아세트산나트륨, 아실화 가수분해 콜라겐펩티드염, 퍼플루오로알킬인산에스테르 등을 들 수 있다.Anionic surfactants include fatty acid soaps, alpha-acyl sulfonates, alkyl sulfonates, alkyl allyl sulfonates, alkyl naphthalene sulfonates, alkyl sulfates, POE alkyl ether sulfates, alkylamide sulfates, alkyl phosphates, POE alkylphosphates, and alkylamides. Phosphates, alkyloylalkyltaurine salts, N-acylamino acid salts, POE alkyl ether carboxylate salts, alkyl sulfosuccinate salts, sodium alkyl sulfo acetates, acylated hydrolyzed collagen peptide salts, perfluoroalkyl phosphate esters, and the like. have.

양이온성 계면 활성제로서는 염화알킬트리메틸암모늄, 염화스테아릴트리메틸암모늄, 브롬화스테아릴트리메틸암모늄, 염화세토스테아릴트리메틸암모늄, 염화디 스테아릴디메틸암모늄, 염화스테아릴디메틸벤질암모늄, 브롬화베헤닐트리메틸암모늄, 염화벤잘코늄, 스테아르산디에틸아미노에틸아미드, 스테아르산디메틸아미노프로필아미드, 라놀린 유도체 제 4급 암모늄염 등을 들 수 있다.Examples of cationic surfactants include alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium chloride, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium, behenyltrimethylammonium bromide, and chlorides. Benzalkonium, diethylaminoethyl stearate, dimethylaminopropyl stearate, lanolin derivatives, quaternary ammonium salts, and the like.

양성 계면 활성제로서는 카르복시베타인형, 아미드베타인형, 술포베타인형, 히드록시술포베타인형, 아미드술포베타인형, 포스포베타인형, 아미노카르복실산염형, 이미다졸린 유도체형, 아미드아민형 등의 양성 계면 활성제 등을 들 수 있다.Examples of amphoteric surfactants include the carboxybetaine type, the amide betain type, the sulfobetain type, the hydroxysulfobetain type, the amide sulfobetain type, the phosphobetaine type, the aminocarboxylate type, the imidazoline derivative type, and the amideamine type. An amphoteric surfactant etc. are mentioned.

유기 및 무기 안료로서는 규산, 무수규산, 규산마그네슘, 탤크, 세리사이트, 마이카, 카올린, 벵갈라, 클레이, 벤토나이트, 티탄피막운모, 옥시염화비스무트, 산화지르코늄, 산화마그네슘, 산화아연, 산화티탄, 산화알루미늄, 황산칼슘, 황산바륨, 황산마그네슘, 탄산칼슘, 탄산마그네슘, 산화철, 군청, 산화크롬, 수산화크롬, 칼라민 및 이들의 복합체등의 무기 안료 ; 폴리아미드, 폴리에스테르, 폴리프로필렌, 폴리스티렌, 폴리우레탄, 비닐수지, 요소수지, 페놀수지, 불소수지, 규소수지, 아크릴수지, 멜라민수지, 에폭시수지, 폴리카보네이트수지, 디비닐벤젠ㆍ스티렌 공중합체, 실크파우더, 셀룰로오스, CI 피그먼트옐로우, CI 피그먼트오렌지 등의 유기 안료 및 이들의 무기 안료와 유기 안료의 복합 안료 등을 들 수 있다.Examples of the organic and inorganic pigments include inorganic pigments such as silicic acid, silicic anhydride, magnesium silicate, talc, sericite, mica, kaolin, Bengala, clay, bentonite, titanium mica, titanium oxide, bismuth chloride, zirconium oxide, magnesium oxide, Inorganic pigments such as calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, chromium oxide, chromium oxide, chromium hydroxide, Polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluorine resin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene, styrene copolymer, Organic pigments such as silk powder, cellulose, CI pigment yellow, CI pigment orange, and composite pigments of these inorganic pigments and organic pigments;

유기 분체로서는 스테아르산칼슘 등의 금속비누 ; 세틸린산아연나트륨, 라우릴린산아연, 라우릴린산칼슘 등의 알킬인산금속염 ; N-라우로일-베타-알라닌칼슘, N-라우로일-베타-알라닌아연, N-라우로일글리신칼슘 등의 아실아미노산 다가금속염 ; N-라우로일-타우린칼슘, N-팔미토일-타우린칼슘 등의 아미드술폰산 다가금속염 ; N-엡실론-라우로일-L-리진, N-엡실론-팔미토일리진, N-알파-파리토일올니틴, N- 알파-라우로일아르기닌, N-알파-경화우지지방산아실아르기닌 등의 N-아실염기성아미노산 ; N-라우로일글리실글리신 등의 N-아실폴리펩티드 ; 알파-아미노카프릴산, 알파-아미노라우린산 등의 알파-아미노지방산 ; 폴리에틸렌, 폴리프로필렌, 나일론, 폴리메틸메타크릴레이트, 폴리스티렌, 디비닐벤젠ㆍ스티렌 공중합체, 사불화에틸렌 등을 들 수 있다.As organic powder, Metal soaps, such as a calcium stearate; Alkyl phosphate metal salts such as sodium cetylinate, zinc lauryl acid and calcium laurate; Acylamino acid polyvalent metal salts such as N-lauroyl-beta-alanine calcium, N-lauroyl-beta-alanine zinc, and N-lauroylglycine calcium; Amide sulfonic acid polyvalent metal salts, such as N-lauroyl-taurine calcium and N-palmitoyl-taurine calcium; N, such as N-epsilon-lauroyl-L-lysine, N-epsilon-palmitolyzine, N-alpha-paratoylol nitin, N-alpha-lauroyl arginine, and N-alpha- hardened fatty acid acyl arginine -Acyl basic amino acid; N-acyl polypeptides, such as N-lauroyl glycyl glycine; Alpha-amino fatty acids such as alpha-aminocaprylic acid and alpha-aminolauric acid; Polyethylene, polypropylene, nylon, polymethyl methacrylate, polystyrene, divinylbenzene-styrene copolymer, ethylene tetrafluoride and the like.

자외선 흡수제로서는 파라아미노벤조산, 파라아미노벤조산에틸, 파라아미노벤조산아밀, 파라아미노벤조산옥틸, 살리실산에틸렌글리콜, 살리신산페닐, 살리신산옥틸, 살리신산벤질, 살리신산부틸페닐, 살리신산호모멘틸, 계피산벤질, 파라메톡시계피산-2-에톡시에틸, 파라메톡시계피산옥틸, 디파라메톡시계피산모노-2-에틸헥산글리세릴, 파라메톡시계피산이소프로필, 디이소프로필ㆍ디이소프로필계피산에스테르 혼합물, 우로카닌산, 우로카닌산에틸, 히드록시메톡시벤조페논, 히드록시메톡시벤조페논술폰산 및 그 염, 디히드록시메톡시벤조페논, 디히드록시메톡시벤조페논디술폰산나트륨, 디히드록시벤조페논, 테트라히드록시벤조페논, 4-tert-부틸-4'-메톡시디벤조일메탄, 2,4,6-트리아닐리노-p-(카르보-2'-에틸헥실-1'-옥시)-1,3,5-트리아진, 2-(2-히드록시-5-메틸페닐)벤조트리아졸 등을 들 수 있다.Examples of the ultraviolet absorber include paraaminobenzoic acid, ethyl paraaminobenzoate, amyl paraaminobenzoic acid, octyl paraaminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomentyl salicylic acid and benzyl cinnamic acid. , Paramethoxy cinnamic acid-2-ethoxyethyl, paramethoxy cinnamic acid octyl, diparamethoxy cinnamic acid mono-2-ethylhexaneglyceryl, paramethoxy cinnamic acid isopropyl, diisopropyl diisopropyl cinnamic acid ester mixture, wuro Canonic acid, ethyl urokanoate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenonesulfonic acid and salts thereof, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium sulfonate, dihydroxybenzophenone , Tetrahydroxybenzophenone, 4- tert -butyl-4'-methoxydibenzoylmethane, 2,4,6-trianilino- p- (carbo-2'-ethylhexyl-1'-oxy) -1 , 3,5-triazine, 2- (2-hi And the like can be mentioned hydroxy-5-methylphenyl) benzotriazole.

살균제로서는 히노키티올, 트리클로산, 트리클로로히드록시디페닐에테르, 크로르헥시딘글루콘산염, 페녹시에탄올, 레조르신, 이소프로필메틸페놀, 아줄렌, 살리칠산, 진크필리티온, 염화벤잘코늄, 감광소 301호, 모노니트로과이어콜나트륨, 운데시렌산 등을 들 수 있다.As fungicides, hinokithiol, trichloric acid, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, ginxitlionone, benzalkonium chloride, photosensitive Sodium No. 301, sodium mononitrohydrol, undecylenic acid, and the like.

산화 방지제로서는 부틸히드록시아니솔, 갈릭산프로필, 엘리소르빈산 등을 들 수 있다.Examples of the antioxidant include butylhydroxyanisole, propyl gallic acid, and erythorbic acid.

pH 조정제로서는 시트르산, 시트르산나트륨, 말산, 말산나트륨, 프말산, 프말산나트륨, 숙신산, 숙신산나트륨, 수산화나트륨, 인산일수소나트륨 등을 들 수 있다.Examples of the pH adjuster include citric acid, sodium citrate, malic acid, sodium malate, fmaric acid, sodium pmarate, succinic acid, sodium succinate, sodium hydroxide, sodium dihydrogen phosphate, and the like.

알코올로서는 세틸알코올 등의 고급 알코올을 들 수 있다.Examples of the alcohol include higher alcohols such as cetyl alcohol.

또한, 이외에 첨가해도 되는 배합 성분은 이에 한정되는 것은 아니며, 상기 어느 성분도 본 발명의 목적 및 효과를 손상시키지 않는 범위 내에서 배합 가능하지만, 총 중량에 대하여 바람직하게는 0.01 내지 5 % 중량 백분율, 보다 바람직하게는 0.01 내지 3 % 중량 백분율로 배합된다.In addition, the compounding component which may be added other than this is not limited to this, Although any said component can be mix | blended within the range which does not impair the objective and effect of this invention, Preferably it is 0.01 to 5% weight percentage with respect to a total weight, More Preferably 0.01 to 3% by weight.

본 발명의 화장료는 용액, 유화물, 점성형 혼합물 등의 형상을 취할 수 있다.The cosmetic of the present invention may take the form of a solution, an emulsion, a viscous mixture or the like.

본 발명의 화장료 조성물에 포함되는 성분은 유효성분으로서 상기 추출물 또는 화합물 이외에 화장료 조성물에 통상적으로 이용되는 성분들을 포함할 수 있으며, 예를 들면, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제 및 담체를 포함한다.Components included in the cosmetic composition of the present invention may include components commonly used in cosmetic compositions in addition to the extract or compound as an active ingredient, for example, such as stabilizers, solubilizers, vitamins, pigments and flavorings Phosphorus aids and carriers.

본 발명의 화장료 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어 유액, 크림, 화장수, 팩, 파운데이션, 로션, 미용액, 모발화장료 등을 들 수 있다.The cosmetic composition of the present invention may be prepared in any formulation commonly prepared in the art, and includes, for example, milky lotion, cream, lotion, pack, foundation, lotion, essence, hair cosmetic, and the like.

본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물섬유, 식물섬유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the present invention is a paste, cream or gel, animal carriers, vegetable fibers, waxes, paraffins, starches, tracantes, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide, etc. may be used as carrier components. Can be.

본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.In the case where the formulation 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, a mixture of chlorofluorohydrocarbons, propane / Propane or dimethyl ether.

본 발명의 제형이 용액 또는 유탁액의 경우에는 담체 성분으로서 용매, 용매화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.In the case of the solution or emulsion of the present invention, a solvent, a solvent or an emulsifier is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.When the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

본 발명의 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 리놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is a surfactant-containing cleansing, the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide. Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

본 발명의 섬오갈피나무 추출물 또는 이로부터 분리한 신규화합물 acankoreoside J가 모발의 성장에 중요한 역할을 하는 모유두세포(Dermal papilla cell)의 성장증식 효과를 나타내므로, 탈모 방지 및 발모 개선용 피부외용 약학 조성물 및 화장료 조성물로 이용될 수 있다.Since the island extract of the present invention, or a new compound acankoreoside J isolated from it shows the growth proliferation effect of dermal papilla cells that play an important role in hair growth, hair loss prevention and hair growth pharmaceutical composition for improving hair growth And cosmetic compositions.

이하, 본 발명을 참고예, 실시예 및 실험예에 의해 상세히 설명한다. Hereinafter, the present invention will be described in detail by reference examples, examples and experimental examples.

단, 하기 참고예, 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 참고예, 실시예 및 실험예에 한정되는 것은 아니다.However, the following Reference Examples, Examples, and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Reference Examples, Examples, and Experimental Examples.

실시예Example 1. 섬오갈피나무 추출물의 제조 1. Preparation of Pleurotus eryngii Extract

1-1. 섬오갈피나무 줄기 추출물의 제조1-1. Preparation of Stem Extract

섬오갈피나무 재배지에서 채취한 섬오갈피나무(Acanthopanax koreanum)의 줄기를 자연건조한 후 절편하여 100 g을 1 ℓ의 100% 주정, 50% 주정 및 증류수에 각각 넣고 90 ℃이상의 온도에서 3시간동안 2회 반복 추출하였다. 추출액은 여과지(Whatman사)로 여과한 후, 감압농축(Eyela, Rotary Evaporator N-1000) 및 동결건조(Eyela, Freeze Dryer FDU-540)하여 줄기의 100% 주정추출물(AS1) 8.7 g(수득 율: 8.7%), 줄기의 50% 주정추출물(AS2) 11.5 g(수득율: 11.5%) 및 줄기의 물추출물(AS3) 18.5 g(수득율: 18.5%)을 각각 수득하여 하기 실험예의 시료로 사용하였다.Island taken from the island senticosus tree plantations senticosus wood (Acanthopanax The stems of koreanum ) were naturally dried and then sliced into 100 g of 1 L 100% alcohol, 50% alcohol and distilled water, respectively, and extracted twice over 3 hours at a temperature of 90 ° C. or higher. The extract was filtered with filter paper (Whatman), concentrated under reduced pressure (Eyela, Rotary Evaporator N-1000) and freeze-dried (Eyela, Freeze Dryer FDU-540) to obtain 8.7 g of 100% alcohol extract (AS1) from the stem. : 8.7%), 50% alcohol extract (AS2) 11.5 g (yield: 11.5%) of the stem and 18.5 g (yield: 18.5%) of the water extract (AS3) of the stem were obtained and used as a sample of the following experimental example.

1-2. 섬오갈피나무 뿌리 추출물의 제조1-2. Preparation of Citrus Root Extract

섬오갈피나무 재배지에서 채취한 섬오갈피나무(Acanthopanax koreanum)의 뿌리를 자연건조한 후 절편하여 사용하는 것을 제외하고는 상기 실시예 1-1과 동일한 공정을 수행하여 뿌리의 100% 주정추출물(AR1) 8.3 g(수득율: 8.3%), 뿌리의 50% 주정추출물(AR2) 12.5 g(수득율: 12.5%) 및 뿌리의 물추출물(AR3) 16.5 g(수득율: 16.5%)을 각각 수득하여 하기 실험예의 시료로 사용하였다.Island taken from the island senticosus tree plantations senticosus wood (Acanthopanax Koreanum ) 100 g of alcoholic extract (AR1) 8.3 g (yield: 8.3%), 50% of the roots were subjected to the same process as in Example 1-1, except that the roots of the Koreanum were naturally dried and then sliced . 12.5 g (yield: 12.5%) of alcohol extract (AR2) and 16.5 g (yield: 16.5%) of water extract (AR3) of root were obtained, and used as a sample of the following experimental example.

1-3. 섬오갈피나무 잎 추출물의 제조1-3. Preparation of Scorpion Leaf Extract

섬오갈피나무 재배지에서 채취한 섬오갈피나무(Acanthopanax koreanum)의 잎을 자연건조한 후 절편하여 사용하는 것을 제외하고는 상기 실시예 1-1과 동일한 공정을 수행하여 잎의 100% 주정추출물(AL1) 8.2 g(수득율: 8.2%), 잎의 50% 주정추출물(AL2) 13.5 g(수득율: 13.5%) 및 잎의 물추출물(AL3) 26.2 g(수득율: 26.2%)을 각각 수득하여 하기 실험예의 시료로 사용하였다.Island taken from the island senticosus tree plantations senticosus wood (Acanthopanax Koreanum ) 100 g of alcohol extract (AL1) 8.2 g (yield: 8.2%), 50% of the leaves were subjected to the same process as in Example 1-1, except that the leaves of the Koreanum were dried and then sliced . 13.5 g (yield: 13.5%) of alcohol extract (AL2) and 26.2 g (yield: 26.2%) of water extract (AL3) of the leaves were obtained and used as samples in the following experimental example.

실시예Example 2. 신규화합물  2. New Compound acankoreosideacankoreoside J의 분리 Separation of J

2-1. 섬오갈피나무 잎으로부터 2-1. From the leaves of the island AKAK -10 분리정제-10 Separation Purification

섬오갈피나무 재배지에서 채취한 섬오갈피나무(Acanthopanax koreanum)의 잎 3.5 kg을 건조하여 세절한 후, 60 ℃에서 100% 메탄올 9 ℓ로5시간동안 3회 열수 추출한 다음, 여과하여 얻은 추출액을 감압농축하여 메탄올엑스 약 550 g을 수득하였다. 수득한 메탄올엑스 540 g에 증류수 1 ℓ 및 헥산(Hexane) 1.5 ℓ를 가하고 진탕하여 헥산층과 수층으로 분획한 후, 헥산층을 감압농축하여 헥산 분획물 54 g을 수득하였다. 수층 1.5 ℓ에 에틸아세테이트 1.5 ℓ를 가하고 진탕하여 에틸아세테이트층과 수층으로 나눈 다음, 에틸아세테이트층과 수층을 각각 감압농축하여 에틸아세테이트 분획물 91.3 g 및 수가용성 분획물 403.7 g을 수득하였다. 수득한 수가용성 분획물을 Diaion HP-20 컬럼에 로딩한 후, 물과 메탄올을 이동상으로 하여 용매 구배(100% 물, 90% 메탄올, 75% 메탄올, 50% 메탄올, 20% 메탄올, 100% 메탄올)로 용출하였다. 얻어진 50% 메탄올 분획 30.0 g을 실리카겔과 YMC RP-18 컬럼 크로마토그래피를 반복수행하여 백색의 무정형 분말(AK-10) 70 mg을 수득하였다.Island taken from the island senticosus tree plantations senticosus wood (Acanthopanax 3.5 kg of the leaves of koreanum ) were dried and chopped , and then extracted with hot water three times for 5 hours with 9 L of 100% methanol at 60 ° C., and the extract was filtered under reduced pressure to give about 550 g of methanol extract. 1 L of distilled water and 1.5 L of hexane were added to 540 g of the obtained methanol extract, followed by shaking. The mixture was partitioned into a hexane layer and an aqueous layer. The hexane layer was concentrated under reduced pressure to obtain 54 g of a hexane fraction. 1.5 L of ethyl acetate was added to 1.5 L of aqueous layer, shaken, and divided into an ethyl acetate layer and an aqueous layer. The ethyl acetate layer and the aqueous layer were concentrated under reduced pressure, respectively, to obtain 91.3 g of ethyl acetate fraction and 403.7 g of a water-soluble fraction. The obtained water-soluble fraction was loaded onto a Diaion HP-20 column, and then a solvent gradient (100% water, 90% methanol, 75% methanol, 50% methanol, 20% methanol, 100% methanol) with water and methanol as mobile phases. Eluted. Silica gel and YMC RP-18 column chromatography were repeatedly performed on 30.0 g of the obtained 50% methanol fraction to obtain 70 mg of white amorphous powder (AK-10).

2-2. 2-2. AKAK -10의 구조 동정-10 structure identification

상기 실시예 2-1에서 수득한 AK-10의 MS 스펙트럼(AGILENT, 1200 SERIES LC-MSD Trap spectrometer)을 측정한 결과, m/z 1034.5에서 분자 이온 피크(molecular ion peak)를 나타내었으며, HR-MS 스펙트럼을 측정하여 분자식은 C50H82O22로 추정할 수 있었다. 1H-NMR, 13C-NMR, DEPT 및 HMBC 스펙트럼을 통해서 AK-10은 천연에서 처음으로 분리되는 신규물질로서, 루펜 계(lupane type)의 트리터페노이 드(triterpenoid) 배당체인 신규화합물로 동정하였고, 그 이름을 acankoreoside J로 명명하였다. 하기 표 1에 acankoreoside J [3α,20,29-trihydroxylupan-23,28-dioic acid 28-O-{α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl}ester]의 물성치를 나타내었다.As a result of measuring the MS spectrum (AGILENT, 1200 SERIES LC-MSD Trap spectrometer) of AK-10 obtained in Example 2-1, it showed a molecular ion peak at m / z 1034.5, HR- By measuring the MS spectrum, the molecular formula could be estimated as C 50 H 82 O 22 . Through the 1 H-NMR, 13 C-NMR, DEPT and HMBC spectra, AK-10 is the first new substance to be separated from nature and identified as a novel compound that is a triterpenoid glycoside of the lupane type. And named it acankoreoside J. In Table 1 acankoreoside J [3 α, 20,29 -trihydroxylupan-23,28-dioic acid 28- O - {α -L-rhamnopyranosyl- (1 → 4) - β -D-glucopyranosyl- (1 → 6) - β -D-glucopyranosyl} ester] exhibited the following physical data of the.

No.No. δHδH δCδC DEPT 135DEPT 135 HMBC (H-C)HMBC (H-C) 1One 1.401.40 34.2334.23 CH2 CH 2 22 1.531.53 26.1026.10 CH2 CH 2 33 3.67 (m)*3.67 (m) * 73.3773.37 C1, C5, C24, C1aC1, C5, C24, C1a 44 -- 52.1352.13 -- 55 1.851.85 46.9346.93 CHCH C4, C6, C24, C24, C25C4, C6, C24, C24, C25 66 22.2822.28 CH2 CH 2 77 1.31, 1.571.31, 1.57 35.5235.52 CH2 CH 2 C5, C9C5, C9 88 -- 43.0443.04 -- 99 1.521.52 52.0352.03 CHCH 1010 38.1538.15 1111 22.4822.48 CH2 CH 2 1212 2.202.20 29.8829.88 CH-2 CH -2 1313 2.342.34 39.5039.50 C14C14 1414 -- 44.5844.58 1515 1.17, 1.621.17, 1.62 31.2431.24 CH2 CH 2 C17C17 1616 1.46, 2.351.46, 2.35 33.1833.18 CH2 CH 2 C28C28 1717 -- 60.1260.12 1818 1.741.74 49.5149.51 C17, C19,20, C28C17, C19,20, C28 1919 2.372.37 45.7245.72 CHCH C18, C20, C30C18, C20, C30 2121 2.12.1 28.8928.89 CH2 CH 2 C20C20 2222 1.39, 1.811.39, 1.81 37.5037.50 C17C17 2323 184.29184.29 -- 2424 1.09, 3H, s1.09, 3H, s 18.4518.45 CH3 CH 3 C3, C4, C5, C23C3, C4, C5, C23 2525 0.90, 3H, s0.90, 3H, s 17.4417.44 CH3 CH 3 C1, C5, C9, C10C1, C5, C9, C10 2626 0.96, 3H, s0.96, 3H, s 17.2917.29 CH3 CH 3 C7, C8, C14C7, C8, C14 2727 1.07, 3H, s1.07, 3H, s 15.6215.62 CH3 CH 3 C8, 14C8, 14 2828 177.02177.02 -- 2929 1.04, 3H, s1.04, 3H, s 19.6619.66 CH-3 CH -3 C19, C20, C30C19, C20, C30 3030 3.37 (m)*3.37 (m) * 71.2371.23 C19, C20, C29C19, C20, C29 1a1a 3.56 (m)*3.56 (m) * 73.6273.62 CH2 CH 2 2a2a 3.673.67 62.3562.35 CH2 CH 2 GlcGlc 1One 5.43, 1H, d, 8.55.43, 1H, d, 8.5 95.4495.44 CHCH C28, C3, C5C28, C3, C5 22 3.33 (m)*3.33 (m) * 73.9873.98 CHCH C1, C2C1, C2 33 3.43 (m)*3.43 (m) * 78.3378.33 CHCH 44 3.42 (m)*3.42 (m) * 71.1471.14 CHCH 55 3.43 (m)*3.43 (m) * 78.2178.21 CHCH 66 3.78, 1H, d, 5.03.78, 1 H, d, 5.0 69.6669.66 CH2 CH 2 C4, C5C4, C5 4.101H, 1H, d, 10.54.101H, 1H, d, 10.5 Glc'Glc ' 1'One' 4.39, 1H, d, 8.04.39, 1H, d, 8.0 104.61104.61 CHCH C6, C5'C6, C5 ' 2'2' 3.24, 1H, t, 8.03.24, 1H, t, 8.0 75.4375.43 CHCH C1, C3C1, C3 3'3 ' 3.46(m)3.46 (m) 76.8176.81 CHCH C2, C4C2, C4 4'4' 3.54, 1H, t3.54, 1H, t 79.6879.68 CHCH C3', C5'C3 ', C5' 5'5 ' 3.29 (m)*3.29 (m) * 76.9976.99 CHCH 6'6 ' 3.66, 3.823.66, 3.82 62.0262.02 CH2 CH 2 C4', C5'C4 ', C5' RhaRha 1One 4.84, 1H, d, 9.04.84, 1 H, d, 9.0 103.03103.03 CHCH C2", C5"C2 ", C5" 22 3.64 (m)*3.64 (m) * 72.2772.27 CHCH 33 3.83 (m)*3.83 (m) * 72.5572.55 CHCH C2, C4C2, C4 44 3.40 (m)*3.40 (m) * 73.8473.84 CHCH C5", C6"C5 ", C6" 55 3.96, 1H, dd, 5.5, 8.53.96, 1H, dd, 5.5, 8.5 70.7870.78 CHCH C4", C6"C4 ", C6" 66 1.27, 3H, d, 6.01.27, 3H, d, 6.0 18.0018.00 CH3 CH 3 C4", C5"C4 ", C5"

참고예 1. 통계 분석Reference Example 1. Statistical Analysis

모든 측정결과는 평균 ± 표준편차로 나타내었으며, 통계학적 유의성 검정은 student's t test으로 검정하였으며, p-value가 0.05이하일 경우 유의성을 인정하였다. 통계처리는 SPSS 12.0K for Windows(Release 12.0.1. SPSS Inc. USA)를 사용하였다.All results were expressed as mean ± standard deviation. Statistical significance test was performed by student's t test, and the significance was recognized when p-value was less than 0.05. For statistical processing, SPSS 12.0K for Windows (Release 12.0.1. SPSS Inc. USA) was used.

실험예 1. 모유두세포(Dermal papilla cell)의 증식 효과 측정Experimental Example 1. Measurement of the proliferation effect of dermal papilla cells

상기 실시예에서 수득한 섬오갈피나무 추출물 또는 이로부터 분리한 신규화합물 acankoreoside J가 모발의 성장에 매우 중요한 역할을 하는 모유두세포 증식 효과가 있는지 확인하기 위하여 불멸화된 모낭유두 세포(rat vibrissa immortalized dermal papilla cell)를 사용하여 문헌에 기재된 방법을 이용하여 하기와 같이 MTT 분석법으로 실험하였다(Han JH, et al., Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle., J Dermatol Sci, 34, pp.91-98, 2004).Immortalized dermal papilla cells (rat vibrissa immortalized dermal papilla cell) in order to confirm whether or not the extract of the island of the islands obtained in the above example or the new compound acankoreoside J isolated therefrom has a proliferative effect on dermal papilla cells that play a very important role in hair growth (Han JH, et al ., Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle., J Dermatol Sci , 34 ,). pp. 91-98, 2004).

흰쥐 수염에서 분리된 모낭 유두 세포를 불멸화한 세포(Rat vibrissa immortalized dermal papilla cell; Filsell W, et al., Transfection of rat dermal papilla cells with a gene encoding a temperature-sensitive polyomavirus large T antigen generates cell lines a differentiated phenotype., J. Cell Sci, 107, pp.1761-1772, 1994)를 100 units/㎖ 페니실린-100 ㎍/㎖ 스트렙토마이신(streptomycin; Gibco Inc, NY, USA)과 10% 열-비활성화 FBS(heat-inactivated fetal bovine serum; Gibco Inc, NY, USA)가 함유된 DMEM(Hyclone Inc, USA) 배지를 사용하여 37℃, 5% CO2 항온기에서 배양하였으며, 3 일에 한 번씩 계대배양 하였다.Rat vibrissa immortalized dermal papilla cells; Filsell W, et al ., Transfection of rat dermal papilla cells with a gene encoding a temperature-sensitive polyomavirus large T antigen generates cell lines a differentiated phenotype., J. Cell Sci , 107 , pp. 1761-1772, 1994) with 100 units / ml penicillin-100 μg / ml streptomycin (Gibco Inc, NY, USA) and 10% heat-inactivated FBS (heat DMEM (Hyclone Inc, USA) medium containing -inactivated fetal bovine serum; Gibco Inc, NY, USA) was incubated in a 37 ° C., 5% CO 2 incubator and passaged once every 3 days.

상기에서 배양한 모유두세포(1.0×104 cells/㎖)를 96-웰 플레이트에 넣고 24시간 배양한 후, 무혈청 DMEM 배지로 교환하여 다시 24시간 배양한 다음, 상기 실시예 1에서 수득한 섬오갈피나무 추출물 AS1, AS2, AS3, AR1, AR2, AR3, AL1, AL2 및 AL3은 0.1 및 1 ug/ml의 농도로 각각 처리하였고, 상기 실시예 2에서 분리정제한 순수한 화합물인 AK-10은 0.1 및 1 uM의 농도로 처리하였다. 또한, 양성 대조군인 미녹시딜 설페이트(minoxidil sulfate; Sigma, MO, USA)는 1 μM의 농도로 처리하였다. 4 일 동안 배양한 후 50 ㎕ 의 MTT(Sigma, MO, USA)를 첨가하고 4 시간 동안 반응시켰다. 상층액은 제거하고 DMSO 200 ㎕을 가하여 침전물을 용해시킨 후, 마이크로플레이트 판독기(microplate reader; Amersham Pharmacia Biotech, NY, USA)를 사용하여 540 nm에서 흡광도를 측정하였다. 각 시료군에 대한 평균 흡광도 값을 구하였으며, 대조군의 흡광도 값과 비교하여 증식 정도를 조사하였다.The cultured dermal papilla cells (1.0 × 10 4 cells / ml) were put in a 96-well plate and incubated for 24 hours, then exchanged with serum-free DMEM medium for 24 hours, and then the islands obtained in Example 1 above. Agalophyllum extract AS1, AS2, AS3, AR1, AR2, AR3, AL1, AL2 and AL3 were treated at concentrations of 0.1 and 1 ug / ml, respectively, and the pure compound AK-10 isolated and purified in Example 2 was 0.1 And a concentration of 1 uM. In addition, the minoxidil sulfate (minoxidil sulfate; Sigma, MO, USA) as a positive control was treated at a concentration of 1 μM. After incubation for 4 days, 50 μl of MTT (Sigma, MO, USA) was added and reacted for 4 hours. The supernatant was removed, 200 μl of DMSO was added to dissolve the precipitate, and the absorbance was measured at 540 nm using a microplate reader (Amersham Pharmacia Biotech, NY, USA). The average absorbance value for each sample group was obtained, and the degree of proliferation was investigated by comparing with the absorbance values of the control group.

실험결과, 하기 표 2 , 표 3, 도 1 및 도 2에 나타난 바와 같이, 본 발명의 섬오갈피나무 추출물 AS2(1 ug/ml), AL1(0.1 ug/ml) 및 신규화합물 AK-10(1 uM)을 처리하였을 때, 대조군의 증식효과(100%)와 비교하여 124.3±10.3%, 117.7±7.1% 및 121.3±6.5% (P >0.05)로 유의성 있게 증가하였음을 확인할 수 있었으며, 이런 AS2(1 ug/ml), AL1(0.1 ug/ml) 및 신규화합물 AK-10(1 uM)의 모유두세포(dermal papilla cell) 증식효과는 대표적 모발성장 촉진 약물로 널리 알려진 미녹시딜 설페이트(minoxidil sulfate, M.S.)의 증식 효과(115.8±10.2%)보다 더 탁월한 것을 확인할 수 있었다.Experimental results, as shown in Table 2, Table 3, Figure 1 and Figure 2, the extract of the islands of the present invention AS2 (1 ug / ml), AL1 (0.1 ug / ml) and a novel compound AK-10 (1 uM) was significantly increased to 124.3 ± 10.3%, 117.7 ± 7.1% and 121.3 ± 6.5% ( P > 0.05) compared with the control effect (100%). 1 ug / ml), AL1 (0.1 ug / ml) and new compound AK-10 (1 uM) proliferation effect of dermal papilla cells (minoxidil sulfate (MS), a well-known hair growth promoting drug It was confirmed that the proliferation effect of (115.8 ± 10.2%) is more excellent.

증식률
(%)
Growth rate
(%)
AS1AS1 AS2AS2 AS3AS3 AR1AR1 AR2AR2 AR3AR3 AL1AL1 AL2AL2 AL3AL3 M.S.
(1uM)
MS
(1 uM)
0.1ug/ml0.1ug / ml 104.8±10.8104.8 ± 10.8 113.6±12.0113.6 ± 12.0 104.7±6.9104.7 ± 6.9 103.7±11.4103.7 ± 11.4 97.7±7.4 97.7 ± 7.4 111.3±12.08 111.3 ± 12.08 117.7±7.1* 117.7 ± 7.1 * 115.0±8.4115.0 ± 8.4 116.4±7.4116.4 ± 7.4 115.8±10.2115.8 ± 10.2 1ug/ml1ug / ml 108.4±8.6108.4 ± 8.6 124.3±10.3*124.3 ± 10.3 * 106.8±4.9106.8 ± 4.9 111.2±13.0111.2 ± 13.0 99.1±4.899.1 ± 4.8 113.4±7.8113.4 ± 7.8 94.6±9.394.6 ± 9.3 115.5±11.9115.5 ± 11.9 112.7±9.5112.7 ± 9.5 무처리 대조군(100%)과 비교Comparison with no control group (100%)

증식률(%)Proliferation rate (%) acankoreoside J (AK-10)acankoreoside J (AK-10) M.S.M.S. 0.1 uM0.1 uM 97.2±5.597.2 ± 5.5 1 uM1 uM 121.3±6.5*121.3 ± 6.5 * 115.8±10.2115.8 ± 10.2 무처리 대조군(100%)과 비교Comparison with no control group (100%)

실험예Experimental Example 2. 콧수염 모낭( 2. Mustache hair follicles ( VibrissaVibrissa folliclesfollicles ) 성장 효과 측정 ) Growth effect measurement

2-1. 2-1. 랫트의Rat 콧수염 모낭( Mustache hair follicles ( RatRat vibrissavibrissa folliclesfollicles )의 분리 및 배양Isolation and Cultivation

상기 실시예 2의 신규 화합물인 AK-10의 육모 효능을 측정하기 위하여 문헌에 기재된 방법을 이용하여 하기와 같은 실험을 수행하였다(Philpott MP, et al., Cyclical changes in rat vibrissa follicles maintained in vitro. J Invest Dermatol . 115, pp.1152-1155, 2000). In order to measure the hair growth efficacy of AK-10, a novel compound of Example 2, the following experiment was performed using the method described in the literature (Philpott MP, et. al ., Cyclical changes in rat vibrissa follicles maintained in in vitro . J Invest Dermatol . 115 , pp. 1152-1155, 2000).

생후 3주령인 위스터 랫트(Wistar rat) 수컷(Japan SLC, Hamamatsu, Janpan)을 (주)중앙실험동물로부터 구입하여 에틸 에테르(ethyl ether)로 마취한 후 경추도살 하였다. 랫트 왼쪽과 오른쪽 상순(mystacial pads)을 분리하여 100 units/㎖ 페니실린-100 ㎍/㎖ 스트렙토마이신(Gibco Inc, NY, USA)이 함유된 E/P buffer[(EBSS, Earle's balanced salts solution, Sigma MO, USA) + (PBS, phosphate-buffered saline, Sigma MO, USA)]에 넣었다. 해부 현미경으로 관찰하며 콧수염 모낭(vibrissa follicles)을 조심스럽게 분리하였다. 모낭이 모두 분리될 때까지 E/P buffer를 넣은 페트리 디쉬(Petri dish)에 분리된 모낭을 넣고 37 ℃, 5% CO2 항온기에서 1시간 정도 배양하였다. 24-웰 플레이트의 각 웰에 2 mM L-글루타민(L-glutamine, Gibco Inc, NY, USA), 10 ㎍/㎖ 인슐린(insulin, Sigma MO, USA), 50 nM 하이드로코르티손(hydrocortisone, Sigma MO, USA)과 100 units/㎖ 페니실린-100 ㎍/㎖ 스트렙토마이신을 포함하는 500 ㎕의 윌리엄 E 배지(William E medium, Gibco Inc, NY, USA)를 넣고, 하나의 웰에 하나씩의 모낭을 넣어서 37 ℃, 5% CO2 항온기에서 배양하였다. 한 실험군에 10-12개의 모낭을 이용하였으며, 배양 중에 배지는 3일마다 교환하였다. 상기 실시예 2의 신규 화합물인 AK-10을 0.1, 1 및 10 uM 농도로 처리하였으며, 양성 대조물질인 미녹시딜 설페이트(minoxidil sulfate, M.S., Sigma, USA)는 1 μM의 농도로 처리하였다.Three-week-old male Wistar rats (Japan SLC, Hamamatsu, Janpan) were purchased from a central laboratory animal, anesthetized with ethyl ether and cervical slaughtered. Rat left and right mystacial pads were isolated to isolate E / P buffer [(EBSS, Earle's balanced salts solution, Sigma MO) containing 100 units / ml penicillin-100 μg / ml streptomycin (Gibco Inc, NY, USA). , USA) + (PBS, phosphate-buffered saline, Sigma MO, USA)]. The vibrissa follicles were carefully separated while observing under a dissecting microscope. Until the hair follicles were separated, the separated hair follicles were placed in a Petri dish containing E / P buffer and incubated at 37 ° C. in a 5% CO 2 thermostat for about 1 hour. In each well of a 24-well plate 2 mM L-glutamine (L-glutamine, Gibco Inc, NY, USA), 10 μg / ml insulin (insulin, Sigma MO, USA), 50 nM hydrocortisone (Sigma MO, USA) and 500 μl of William E medium (William E medium, Gibco Inc, NY, USA) containing 100 units / ml penicillin-100 μg / ml streptomycin and put one follicle into one well at 37 ° C. , 5% CO 2 incubator. 10-12 hair follicles were used in one experimental group, and the medium was changed every 3 days during the culture. AK-10, a novel compound of Example 2, was treated at concentrations of 0.1, 1, and 10 uM, and minoxidil sulfate (minoxidil sulfate, MS, Sigma, USA), a positive control, was treated at a concentration of 1 μM.

2-2. 콧수염 모낭(2-2. Mustache hair follicles ( RatRat vibrissavibrissa folliclesfollicles )의 성장 측정) Growth measurement

배양 중인 콧수염 모낭(vibrissa follicle)의 형태는 현미경(Olympus, Japan)을 사용하여 촬영하였다. 모낭 길이는 이미지 분석기(image analyzer, DP controller; Olympus, Japan)를 사용하여 0, 7, 14 및 21일 째에 측정하였다. 모낭 길이 변화의 평균값을 구하고 대조군의 평균길이와 비교하여 성장 정도를 측정하였다. The morphology of the cultured mustache follicle (vibrissa follicle) was photographed using a microscope (Olympus, Japan). Hair follicle length was measured on day 0, 7, 14 and 21 using an image analyzer (DP controller; Olympus, Japan). The average value of the hair follicle length change was calculated and compared with the average length of the control group.

2-3. 실험결과2-3. Experiment result

실험결과, 생후 3 주령 랫트의 성장기 콧수염 모낭(vibrissa follicles)을 분리하여 3주간 배양하면서 모낭 길이를 측정함으로써 실시예 2의 신규 화합물인 AK-10의 육모 효능을 확인하였다. 도 3에 나타난 바와 같이, AK-10 처리군과 대조군과의 모낭의 길이 차이(%)를 비교한 결과, AK-10을 0.1 uM 농도로 처리하였을 때, 21일째에 모섬유질(hair fiber)의 성장 효과는 대조군(100%)보다 118.1±12.0% (P>0.05)로 유의성 있게 증가하였으며, 양성대조군인 1 uM 미녹시딜 설페이트(minoxidil sulphate, M.S.)는 112.9±10.2% 성장 효과를 확인할 수 있었다. As a result, the growth of the three-week-old rat growth period mustache follicles (vibrissa follicles) was isolated and cultured for three weeks to determine the hair follicle efficacy of the novel compound AK-10 of Example 2 by measuring the hair follicle length. As shown in FIG. 3, a comparison of the length difference (%) of hair follicles between the AK-10 treated group and the control group showed that when AK-10 was treated at a concentration of 0.1 uM, the hair fibers were observed on the 21st day. The growth effect was significantly increased to 118.1 ± 12.0% ( P > 0.05) than the control group (100%), and the positive control group, 1 uM minoxidil sulphate (MS), showed 112.9 ± 10.2% growth effect.

하기에 본 발명의 추출물 또는 화합물을 포함하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, the preparation examples of the composition comprising the extract or the compound of the present invention, but the present invention is not intended to limit it, only intended to explain in detail.

제제예Formulation example 1. 헤어토닉의 제조 1. Preparation of Hair Tonic

레조시놀 0.1%Resorcinol 0.1%

멘톨 0.05%Menthol 0.05%

판테놀 0.2% Panthenol 0.2%

살리실산 0.1%Salicylic Acid 0.1%

토코페릴 아세테이트 0.1%Tocopheryl Acetate 0.1%

염산피리독신 0.1%Pyridoxine hydrochloride 0.1%

피마자유 5.0%Castor Oil 5.0%

AS2(섬오갈피나무 줄기의 50% 주정추출물) 10.0%AS2 (50% spirit extract of island stems) 10.0%

색소 적량Pigment amount

향료 적량Spices

에탄올 적량Ethanol

정제수 잔량Purified water level

계 100.0%Total 100.0%

제제예Formulation example 2.  2. 헤어컨디셔너의Of hair conditioner 제조 Produce

세탄올 3.5%Cetanol 3.5%

자기유화형 모노스테아린산글리세린 1.5%Self-emulsifying glycerin monostearate 1.5%

프로필렌 글리콜 2.5%Propylene Glycol 2.5%

염화스테아릴메틸벤질 암모늄(25%) 7.0%Stearylmethylbenzyl Ammonium Chloride (25%) 7.0%

파라옥시안식향산메틸 0.3%0.3% methyl paraoxybenzoate

AL1(섬오갈피나무 잎의 100% 주정추출물) 2.5%AL1 (100% spirit extract of island ivy leaf) 2.5%

색소 적량Pigment amount

향료 적량Spices

정제수 잔량Purified water level

계 100.0%Total 100.0%

제제예Formulation example 3.  3. 헤어로션의Hair lotion 제조 Produce

레조시놀 2.0%Resorcinol 2.0%

멘톨 2.0%Menthol 2.0%

판테놀 0.5%Panthenol 0.5%

피록톤올아민 0.1%Pyroctonolamine 0.1%

AL2(섬오갈피나무 잎의 50% 주정 추출물) 5.0%AL2 (50% alcohol extract of the leaves of the island of Oak) 5.0%

향료, 색소 0.5%Fragrance, pigment 0.5%

정제수 잔량Purified water level

계 100.0%Total 100.0%

제제예Formulation example 4.  4. 헤어비누의Hair soap 제조 Produce

AL3(섬오갈피나무 잎의 물 추출물) 0.1%AL3 (water extract of Scorpio alba leaves) 0.1%

이산화티탄 0.2%Titanium dioxide 0.2%

폴리에틸렌글리콜 0.8%Polyethylene Glycol 0.8%

글리세린 0.5%Glycerin 0.5%

에틸렌디아민테트라아세트산 0.05%Ethylenediaminetetraacetic Acid 0.05%

나트륨 1.0%Sodium 1.0%

색소 적량Pigment amount

비누향 적량Soap flavor

화장비누베이스 (수분 13%, 중량부) 잔량Cosmetic soap base (13% moisture, parts by weight)

계 100.0%Total 100.0%

제제예Formulation example 5. 친수성 연고제 5. Hydrophilic Ointment

번호number 원 료Raw material 함량(중량%)Content (% by weight) 1One AK-10 (실시예 2)  AK-10 (Example 2) 0.50.5 22 백색 바세린  White vaseline 250250 33 스테아릴 알콜  Stearyl alcohol 220220 44 에칠(또는 메칠)p-옥시벤조에이트  Ethyl (or methyl) p-oxybenzoate 0.250.25 55 프로필렌 글리콜  Propylene glycol 120120 66 라우릴 황산 나트륨  Sodium lauryl sulfate 1515 77 프로필 p-옥시벤조에이트  Propyl p-oxybenzoate 0.150.15

도 1은 실시예 1에서 수득한 섬오갈피나무 추출물의 모유두세포 증식효과를 나타낸 도이며(막대: % of 대조군, 꺾은선: % of 양성대조군 미녹시딜 설페이트),1 is a diagram showing the dermal papilla cell proliferation effect of the extract of S. aureus bark obtained in Example 1 (bar:% of control, broken line:% of positive control minoxidil sulfate),

도 2는 실시예 2에서 분리정제한 신규화합물(AK-10)의 모유두세포 증식효과를 나타낸 도이고(막대: % of 대조군, 꺾은선: % of 양성대조군 미녹시딜 설페이트),Figure 2 is a diagram showing the effect of proliferation of dermal papilla cells of the novel compound (AK-10) isolated and purified in Example 2 (bar:% of control, broken line:% of positive control minoxidil sulfate),

도 3은 실시예 2에서 분리정제한 신규화합물(AK-10)의 콧수염 모낭(vibrissa follicles) 성장 효과를 나타낸 도이다(대조군에 대한 %).3 is a diagram showing the growth effect of vibrissa follicles of the novel compound (AK-10) isolated and purified in Example 2 (% of control).

Claims (7)

섬오갈피나무를 물 및 주정의 혼합용매로 추출한 추출물 또는 이로부터 분리한 하기 구조식(Ⅰ)의 신규화합물 acankoreoside J를 유효성분으로 함유하는 휴지기 탈모증, 원형 탈모증, 생장기 모발 탈모증, 외상성 탈모증, 반흔성 탈모증 또는 비반흔성 탈모증의 방지 및 발모 개선용 피부외용 약학 조성물:Papillary alopecia, alopecia areata, alopecia areata, traumatic alopecia, traumatic alopecia, scarring alopecia containing an extract extracted from an isolaris bark tree with a mixed solvent of water and alcohol or an acankoreoside J of the following structural formula (I) as an active ingredient Or external dermatological pharmaceutical composition for preventing and improving alopecia areata
Figure 112012013436082-pat00002
(Ⅰ)
Figure 112012013436082-pat00002
(Ⅰ)
제 1항에 있어서, 상기 추출물은 섬오갈피나무의 줄기, 뿌리 또는 잎으로부터 수득되는 피부외용 약학 조성물.According to claim 1, wherein the extract is an external skin pharmaceutical composition obtained from the stem, root or leaves of the island. 삭제delete 제 1항에 있어서, 상기 피부외용 약학조성물은 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 또는 카타플라스마제 제형인 피부외용 약학 조성물.The external skin pharmaceutical composition according to claim 1, wherein the external skin pharmaceutical composition is a cream, gel, patch, spray, ointment, warning, lotion, linen, pasta or cataplasma formulation. 삭제delete 섬오갈피나무를 물 및 주정의 혼합용매로 추출한 추출물 또는 이로부터 분리한 제 1항의 신규화합물 acankoreoside J를 유효성분으로 함유하는 휴지기 탈모증, 원형 탈모증, 생장기 모발 탈모증, 외상성 탈모증, 반흔성 탈모증 또는 비반흔성 탈모증의 방지 및 발모 개선용 화장료 조성물.Resting alopecia, alopecia areata, traumatic alopecia, traumatic alopecia, traumatic alopecia, scarring or nasal scar, which contain an extract extracted from an isolaris bark tree with a mixed solvent of water and alcohol or the isolated novel compound acankoreoside J of claim 1 as an active ingredient. Cosmetic composition for preventing and preventing hair loss. 제 6항에 있어서, 상기 화장료 조성물은 헤어토닉, 헤어컨디셔너, 헤어에센 스, 헤어로션, 헤어영양로션, 헤어샴푸, 헤어린스, 헤어트리트먼트, 헤어크림, 헤어영양크림, 헤어모이스처크림, 헤어맛사지크림, 헤어왁스, 헤어 에어로졸, 헤어팩, 헤어영양팩, 헤어비누, 헤어클렌징폼, 머릿기름, 모발건조제, 모발보존처리제, 모발염색제, 모발용 웨이브제, 모발탈색제, 헤어겔, 헤어글레이즈, 헤어드레싱어, 헤어래커, 헤어모이스처라이저, 헤어무스 또는 헤어스프레이의 제형인 화장료 조성물.The method of claim 6, wherein the cosmetic composition is a hair tonic, hair conditioner, hair essence, hair lotion, hair nutrition lotion, hair shampoo, hair rinse, hair treatment, hair cream, hair nutrition cream, hair moisturizer cream, hair massage Cream, hair wax, hair aerosol, hair pack, hair nutrition pack, hair soap, hair cleansing foam, hair oil, hair dryer, hair preservative, hair dye, hair wave, hair bleach, hair gel, hair glaze, hair dresser, A cosmetic composition in the form of a hair lacquer, a hair moisturizer, a hair mousse or a hairspray.
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KR20000024499A (en) * 2000-02-14 2000-05-06 조종원 Hair Loss Prevention & Hair Growth Agent
KR20010000574A (en) * 2000-02-14 2001-01-05 조종원 Hair tonic for hair growth and prevention of depilation
KR100624544B1 (en) 2006-03-10 2006-09-15 김옥순 Compound for preventing loss of hair and method for preparing thereof

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KR20010000574A (en) * 2000-02-14 2001-01-05 조종원 Hair tonic for hair growth and prevention of depilation
KR100624544B1 (en) 2006-03-10 2006-09-15 김옥순 Compound for preventing loss of hair and method for preparing thereof

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