KR102271223B1 - Composition for preventing hair loss and promoting hair growth - Google Patents
Composition for preventing hair loss and promoting hair growth Download PDFInfo
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- KR102271223B1 KR102271223B1 KR1020200090361A KR20200090361A KR102271223B1 KR 102271223 B1 KR102271223 B1 KR 102271223B1 KR 1020200090361 A KR1020200090361 A KR 1020200090361A KR 20200090361 A KR20200090361 A KR 20200090361A KR 102271223 B1 KR102271223 B1 KR 102271223B1
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- South Korea
- Prior art keywords
- composition
- acid
- hair growth
- hair loss
- present
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Classifications
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- A—HUMAN NECESSITIES
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- 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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
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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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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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
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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
- A23V2250/00—Food ingredients
- A23V2250/30—Other Organic compounds
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Abstract
Description
본 발명은 탈모방지 및 발모 촉진용 조성물에 관한 것이다.The present invention relates to a composition for preventing hair loss and promoting hair growth.
현대사회에서 외모에 대한 관심과 함께 모발 건강에 대한 중요성이 더욱 강조되고 있으며, 산업의 발달로 새로운 유해 환경에 노출되는 빈도가 증가하면서, 이에 따른 탈모로 고민하는 인구가 증가하고 있는 추세이다.In modern society, along with interest in appearance, the importance of hair health is more emphasized, and as the frequency of exposure to new harmful environments increases with the development of industry, the population suffering from hair loss is increasing.
모발은 각각 다른 성장주기를 가지는데 모발이 가장 활발하게 성장하는 성장기(Anagen stage), 모발의 퇴화가 시작되는 퇴화기(Catagen stage) 및 모발의 성장이 멈추거나 휴식에 접어드는 휴지기(Telogen stage)의 3단계의 주기를 돌며 발모와 탈모를 반복하며 유지되고 있다. 탈모는 정상적인 현상이나 정상인 사람이 성장기 상태의 모발이 많은 데 비해 탈모증(Alopecia)인 사람은 퇴행기 또는 휴지기에 있는 모발의 비율이 높아짐에 따라 탈락하는 모발의 숫자가 비정상적으로 많아지는 현상이 나타나게 된다.Each hair has a different growth cycle. The growth phase (anagen stage), in which the hair grows most actively, the catagen stage (catagen stage), where hair degeneration begins, and the telogen stage, when hair growth stops or enters a rest period (Telogen stage) It is maintained by repeating hair growth and hair loss in a three-step cycle. Hair loss is a normal phenomenon, but compared to a normal person having a lot of hair in the growth phase, a person with alopecia has an abnormal increase in the number of hair falling out as the proportion of hair in the degenerative or resting phase increases.
탈모의 주 원인 중 하나인 남성호르몬의 일종인 테스토스테론(Testosterone)은 5-알파 환원효소에 의해 디하이드로테스토스테론(Dihydrotestosterone;DHT)으로 활성화되며, DHT가 안드로겐 수용체(Androgen receptor; AR)와 결합하고 탈모를 일으키는 단백질을 유도하여 탈모가 일어난다. DHT는 테스토스테론에 비해 활성이 10배 이상 높기 때문에 5-알파 환원효소를 효율적으로 억제하게 되면 생리적 활성이 강한 DHT의 합성이 감소되어 결국 탈모 방지 또는 발모 촉진의 효과를 가질 수 있다.Testosterone, a type of male hormone that is one of the main causes of hair loss, is activated into dihydrotestosterone (DHT) by 5-alpha reductase, and DHT binds to androgen receptor (AR) and causes hair loss. Hair loss occurs by inducing a protein that causes Since DHT is more than 10 times more active than testosterone, when 5-alpha reductase is effectively inhibited, the synthesis of DHT, which has strong physiological activity, is reduced, and eventually it can have the effect of preventing hair loss or promoting hair growth.
현재 탈모치료제는 미국 식품의약국(Food and Drug Administration of United states, US FDA)으로부터 승인 받은 약물인 5-알파환원효소 저해제 중 경구용 피나스테라이드(Finasteride)와 혈관확장제 중 국소용 미녹시딜(Minoxidil)이 있고, 국내 식품의약품안전처(Korea Ministry of Food and Drug Safety, MFDS)로부터 승인 받은 두타스테라이드(Dutasteride)가 있다. 하지만, 상기 주요 치료제들은 사용을 중단하며 바로 효과가 사라지는 단점이 있다고 알려져 있다. 또한, 치료 적용 시 일부 환자에게서 두피 가려움증 및 피부염 발생의 부작용이 있다고 보고되어 있어 장기적으로 사용해도 부작용이 없는 천연유래물질 개발이 활발히 이루어지고 있다. Currently, hair loss treatments include oral finasteride among 5-alpha reductase inhibitors approved by the Food and Drug Administration of United States (US FDA), and topical minoxidil among vasodilators. , there is Dutasteride approved by the Korea Ministry of Food and Drug Safety (MFDS). However, the main therapeutic agents are known to have a disadvantage that the effect disappears immediately after discontinuation of use. In addition, it has been reported that some patients have side effects of scalp itching and dermatitis when applied for treatment, so development of natural-derived substances that do not have side effects even after long-term use is actively being made.
본 발명은 알려져 있는 탈모 예방 물질의 문제점을 극복하고, 장기적으로 사용해도 부작용이 적은 탈모방지 및 발모 또는 육모 촉진용 조성물을 제공하는 것이다.The present invention overcomes the problems of known hair loss prevention materials, and provides a composition for preventing hair loss and promoting hair growth or hair growth with fewer side effects even when used for a long period of time.
상기 과제를 해결하기 위한 수단으로서, 본 발명은 화학식 1로 표현되는 화합물을 유효성분으로 포함하는 탈모방지 및 발모 촉진용 조성물을 제공한다.As a means for solving the above problems, the present invention provides a composition for preventing hair loss and promoting hair growth comprising the compound represented by Formula 1 as an active ingredient.
[화학식 1][Formula 1]
본 발명의 일 실시예에 의하면 상기 L-테트라하이드로팔마틴의 함량은 상기 조성물의 0.0001~10중량%인 것이 바람직하다.According to an embodiment of the present invention, the content of L-tetrahydro palmatin is preferably 0.0001 to 10% by weight of the composition.
본 발명의 또 다른 목적을 달성하기 위하여, 본 발명은 상기 조성물을 포함하는 탈모방지 또는 발모 촉진용 화장료 조성물을 제공한다.In order to achieve another object of the present invention, the present invention provides a cosmetic composition for preventing hair loss or promoting hair growth comprising the composition.
일 실시예에 의하면 상기 화장료 조성물은 용액, 현탁액, 유탁액, 페이스트, 로션, 파우더, 비누, 계면활성제함유 클린싱 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션, 샴푸, 린스, 토닉 및 스프레이로 구성된 군으로부터 선택되는 제형을 갖는 것이 바람직하다.According to one embodiment, the cosmetic composition is a solution, suspension, emulsion, paste, lotion, powder, soap, surfactant-containing cleansing oil, powder foundation, emulsion foundation, wax foundation, shampoo, rinse, tonic and spray. It is preferred to have a formulation selected from
본 발명의 또 다른 목적을 달성하기 위하여, 본 발명은 상기 조성물을 포함하는 탈모방지 또는 발모 촉진용 기능성 식품 조성물을 제공한다.In order to achieve another object of the present invention, the present invention provides a functional food composition for preventing hair loss or promoting hair growth comprising the composition.
본 발명의 또 다른 목적을 달성하기 위하여, 본 발명은 상기 조성물을 포함하는 탈모방지 또는 발모 촉진용 약제학적 조성물을 제공한다.In order to achieve another object of the present invention, the present invention provides a pharmaceutical composition for preventing hair loss or promoting hair growth comprising the composition.
본 발명에 따른 조성물은 탈모억제 및 발모 또는 육모 촉진 효과를 나타내며, 천연물질로부터 유래한 것으로 인체에 해가 없고 장기 사용시에도 부작용이 없으므로 화장료, 의약품 또는 건강식품에 사용할 수 있다.The composition according to the present invention exhibits an effect of inhibiting hair loss and promoting hair growth or hair growth, is derived from a natural material, has no harm to the human body and has no side effects even when used for a long period of time, so it can be used in cosmetics, pharmaceuticals, or health food.
이하 본 발명을 보다 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명은 하기 화학식 1의 L-테트라하이드로팔마틴(L-tetrahydropalmatine)을 유효성분으로 함유하는 탈모방지 또는 발모 촉진용 조성물을 제공한다. The present invention provides a composition for preventing hair loss or promoting hair growth containing L-tetrahydropalmatine of Formula 1 below as an active ingredient.
[화학식 1][Formula 1]
본 발명에 사용된 상기 화학식 1의 화합물의 화합물명은 L-테트라하이드로팔마틴(L-tetrahydropalmatine)이라 하며, 식물 유래의 사포게닌(sapogenin)의 일종으로서, L-테트라하이드로팔마틴의 효능과 관련하여 항 알레르기 및 항 동맥경화 효능이 있는 것으로 보고되고 있다. The compound name of the compound of Formula 1 used in the present invention is called L-tetrahydropalmatine, and as a kind of plant-derived sapogenin, in relation to the efficacy of L-tetrahydropalmatine It is reported to have anti-allergic and anti-atherosclerotic effects.
본 발명의 용어 "탈모"는 모발이 완전히 두피 밖으로 빠져나오는 현상을 의미한다. As used herein, the term “hair loss” refers to a phenomenon in which hair is completely removed from the scalp.
본 발명의 용어 "발모"는 두피에서 모발이 나는 것을 의미하고, "육모"는 모발의 길이가 길어지는 것(즉, 모발 성장)을 의미하며 당업계에서 이용하는 또 다른 용어인 "양모"와 동일한 의미로 사용된다.The term "hair growth" in the present invention means that hair grows from the scalp, and "hair growth" means that the length of the hair becomes longer (ie, hair growth), and is the same as another term "wool" used in the art. used in meaning
상기 화학식 1의 화합물은 합성하여 이용하거나, 시판되고 있는 화합물을 이용할 수 있다.The compound of Formula 1 may be synthesized and used, or a commercially available compound may be used.
상기 L-테트라하이드로팔마틴의 함량은 상기 조성물의 0.0001~10중량%가 바람직하며, 보다 바람직하게 0.001~5중량%, 보다 더 바람직하게는 0.01~1%중량%로 함유할 수 있다.The content of L-tetrahydro palmatin is preferably 0.0001 to 10% by weight of the composition, more preferably 0.001 to 5% by weight, and even more preferably 0.01 to 1% by weight.
0.0001중량% 미만에서는 모발의 성장 유도 및 탈모 완화 효과가 미미하고, 10 중량% 초과의 농도에서는 제형상 적용이 어려워서 바람직하지 않다.If it is less than 0.0001% by weight, the effect of inducing hair growth and alleviating hair loss is insignificant, and at a concentration of more than 10% by weight, it is not preferable because it is difficult to apply the formulation.
상기 L-테트라하이드로팔마틴은 경구투여 하는 경우에도 독성이 아주 미미하거나 없으므로, 화장료 조성물, 건강기능식품 조성물, 의약품 또는 의약외품 조성물로 사용될 수 있다. Since the L-tetrahydro palmatin has very little or no toxicity even when administered orally, it can be used as a cosmetic composition, a health functional food composition, a pharmaceutical or a quasi-drug composition.
상기 탈모방지 및 모발 성장 촉진용 조성물의 제형은 특별히 한정하지 않으며, 탈모방지 및 모발성장 촉진 효과를 나타내는 것으로서 당업계에 공지된 의약외품의 형태로 다양하게 제형화될 수 있다.The formulation of the composition for preventing hair loss and promoting hair growth is not particularly limited, and it can be variously formulated in the form of quasi-drugs known in the art as exhibiting the effect of preventing hair loss and promoting hair growth.
일 실시예에 의하면, 상기 탈모방지 및 발모 촉진용 조성물은 용액, 현탁액, 유탁액, 페이스트, 로션, 파우더, 비누, 계면활성제함유 클린싱 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션, 샴푸, 린스, 토닉 및 스프레이로 두피 토틱, 두피 로션, 두피 크림, 두피 세럼, 두피 에센스, 두피 앰플, 두피 트리트먼트, 두피 컨디셔너, 두피 샴푸, 두피 팩, 헤어 토닉, 헤어로션, 헤어크림, 헤어스프레이, 헤어무스, 헤어젤, 헤어컨디셔너, 헤어샴푸, 헤어린스, 헤어팩, 헤어트리트먼트, 눈썹발모제, 속눈썹발모제, 속눈썹 영양제, 애완동물용 샴푸, 애완동물용 린스, 손세정제, 세제비누, 비누, 소독청결제, 물티슈, 마스크, 연고제, 패치 또는 필터 충진제 등의 통상적 의미에서의 의약외품, 예를 들어 화장료 조성물로 제공될 수 있으나, 이에 한정되는 것은 아니다. According to one embodiment, the composition for preventing hair loss and promoting hair growth is a solution, suspension, emulsion, paste, lotion, powder, soap, cleansing oil containing surfactant, powder foundation, emulsion foundation, wax foundation, shampoo, conditioner, Scalp tonic, scalp lotion, scalp cream, scalp serum, scalp essence, scalp ampoule, scalp treatment, scalp conditioner, scalp shampoo, scalp pack, hair tonic, hair lotion, hair cream, hair spray, hair mousse, Hair gel, hair conditioner, hair shampoo, hair conditioner, hair pack, hair treatment, eyebrow hair growth agent, eyelash hair growth agent, eyelash nutrition supplement, pet shampoo, pet conditioner, hand sanitizer, detergent soap, soap, disinfectant cleaner, wet wipes, It may be provided as a quasi-drug in a conventional sense such as a mask, ointment, patch or filter filler, for example, a cosmetic composition, but is not limited thereto.
또한, 각 제형에 있어서 탈모 방지 및 모발 성장 촉진용 의약외품 조성물은 다른 성분들을 기타 의약외품의 제형 또는 사용목적 등에 따라 임의로 선정하여 배합할 수 있다. 유효 성분의 혼합량은 사용목적에 따라 적합하게 결정될 수 있고, 예를 들면 점증제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 및 담체 등을 포함할 수 있다.In addition, in each formulation, the quasi-drug composition for preventing hair loss and promoting hair growth may be formulated by selecting other ingredients arbitrarily according to the formulation or purpose of use of other quasi-drugs. The mixing amount of the active ingredient may be suitably determined depending on the intended use, and may include, for example, conventional auxiliary agents such as thickeners, stabilizers, solubilizers, vitamins, pigments and fragrances, and carriers.
본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 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 oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. can
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.When 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, and in particular, in the case of a spray, additional chlorofluorohydrocarbon, propane /may contain propellants such as butane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylglycol oil, glycerol fatty esters, fatty acid esters of polyethylene glycol or sorbitan.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 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, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystals Adult cellulose, aluminum metahydroxide, bentonite, agar or tracanth 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, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is a surfactant-containing cleansing agent, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide as carrier components Ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative or ethoxylated glycerol fatty acid ester and the like can be used.
또한, 본 발명은 L-테트라하이드로팔마틴 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 탈모 방지 또는 개선용, 또는 발모 또는 육모 촉진용 건강기능성 식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving hair loss, or promoting hair growth or hair growth, comprising L-tetrahydro palmatin or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명에 따른 식품 조성물은 당업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다. 일반 식품으로는 이에 한정되지 않지만 음료(알콜성 음료 포함), 과실 및 그의 가공식품(예: 과일통조림, 병조림, 잼, 마아말레이드 등), 어류, 육류 및 그 가공식품(예: 햄, 소시지 콘비이프 등), 빵류 및 면류(예: 우동, 메밀국수, 라면, 스파게이트, 마카로니 등), 과즙, 각종 드링크, 쿠키, 엿, 유제품(예: 버터, 치이즈 등), 식용식물 유지, 마아가린, 식물성 단백질, 레토르트 식품, 냉동식품, 각종 조미료(예: 된장, 간장, 소스 등) 등에 본 발명의 L-테트라하이드로팔마틴을 첨가하여 제조할 수 있다. 또한, 영양보조제로는 이에 한정되지 않지만 캡슐, 타블렛, 환 등에 본 발명의 L-테트라하이드로팔마틴을 첨가하여 제조할 수 있다. 또한, 건강기능식품으로는 이에 한정되지 않지만 예를 들면, 본 발명의 L-테트라하이드로팔마틴 자체를 차, 쥬스 및 드링크의 형태로 제조하여 음용(건강음료)할 수 있도록 액상화, 과립화, 캡슐화 및 분말화하여 섭취할 수 있다. 또한, 본 발명의 L-테트라하이드로팔마틴을 식품 첨가제의 형태로 사용하기 위해서는 분말 또는 농축액 형태로 제조하여 사용할 수 있다. 또한, 본 발명의 L-테트라하이드로팔마틴과 탈모 방지 및 발모 촉진 효과가 있다고 알려진 공지의 활성 성분과 함께 혼합하여 조성물의 형태로 제조할 수 있다.The food composition according to the present invention can be prepared in various forms according to conventional methods known in the art. Common foods include, but are not limited to, beverages (including alcoholic beverages), fruits and their processed foods (eg, canned fruit, canned fruit, jam, marmalade, etc.), fish, meat and their processed foods (eg, ham, sausages) corn beef, etc.), breads and noodles (eg udon noodles, soba noodles, ramen, spagate, macaroni, etc.), fruit juice, various drinks, cookies, syrup, dairy products (eg butter, cheese, etc.), edible vegetable oils and fats, margarine , vegetable protein, retort food, frozen food, various seasonings (eg, soybean paste, soy sauce, sauce, etc.) can be prepared by adding L-tetrahydro palmatin of the present invention. In addition, the nutritional supplement is not limited thereto, but it can be prepared by adding L-tetrahydro palmatin of the present invention to capsules, tablets, pills, and the like. In addition, the health functional food is not limited thereto, but for example, the L-tetrahydro palmatin itself of the present invention is prepared in the form of tea, juice, and drink, and liquefied, granulated, and encapsulated so that it can be consumed (health drink). And it can be ingested by powdering. In addition, in order to use the L-tetrahydro palmatin of the present invention in the form of a food additive, it may be prepared and used in the form of a powder or a concentrate. In addition, it can be prepared in the form of a composition by mixing L-tetrahydro palmatin of the present invention with a known active ingredient known to have an effect of preventing hair loss and promoting hair growth.
본 발명의 L-테트라하이드로팔마틴을 건강음료로 이용하는 경우, 상기 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드; 말토스, 슈크로스와 같은 디사카라이드; 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드; 자일리톨, 소르비톨, 에리트리톨 등의 당알콜일 수 있다. 감미제는 타우마틴, 스테비아 추출물과 같은 천연 감미제; 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 mL 당 일반적으로 약 0.01 ~ 0.04 g, 바람직하게는 약 0.02 ~ 0.03 g 이다. When the L-tetrahydro palmatin of the present invention is used as a health drink, the health drink composition may contain various flavoring agents or natural carbohydrates as additional ingredients like a conventional drink. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrin and cyclodextrin; It may be a sugar alcohol such as xylitol, sorbitol, or erythritol. Sweeteners include natural sweeteners such as taumatin, stevia extract; A synthetic sweetener such as saccharin or aspartame may be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.
또한, 본 발명의 L-테트라하이드로팔마틴은 탈모 방지 및 발모 촉진용 건강기능식품의 유효성분으로 함유될 수 있는데, 그 양은 탈모 방지 및 모발 성장 촉진 효과를 달성하기에 유효한 양으로 특별히 한정되는 것은 아니나, 전체 조성물 총 중량에 대하여 0.01 내지 100 중량%인 것이 바람직하다. 본 발명의 식품 조성물은 L-테트라하이드로팔마틴과 함께 탈모 방지 및 모발 성장 촉진 효과가 있는 것으로 알려진 다른 활성 성분과 함께 혼합하여 제조될 수 있다.In addition, L-tetrahydro palmatin of the present invention may be contained as an active ingredient of a health functional food for preventing hair loss and promoting hair growth, and the amount is particularly limited to an amount effective to achieve the effect of preventing hair loss and promoting hair growth. However, it is preferably 0.01 to 100% by weight based on the total weight of the entire composition. The food composition of the present invention may be prepared by mixing L-tetrahydro palmatin with other active ingredients known to have effects of preventing hair loss and promoting hair growth.
상기 외에 본 발명의 건강식품은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산, 펙트산의 염, 알긴산, 알긴산의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올 또는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강식품은 천연 과일주스, 과일주스 음료, 또는 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health food of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acid, pectic acid salts, alginic acid, alginic acid salts, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, It may contain glycerin, alcohol or a carbonation agent and the like. In addition, the health food of the present invention may contain fruit for the production of natural fruit juice, fruit juice beverage, or vegetable beverage. These components may be used independently or in combination. The proportion of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명의 탈모방지 또는 발모촉진용 약학적 조성물은 상기 화학식 1의 화합물의 약제학적으로 허용 가능한 염을 포함할 수 있다. The pharmaceutical composition for preventing hair loss or promoting hair growth of the present invention may include a pharmaceutically acceptable salt of the compound of Formula 1 above.
상기 L-테트라하이드로팔마틴은 바람직하게는 피부외용 조성물로서, 본 발명의 L-테트라하이드로팔마틴을 유효성분으로 포함하는 피부외용 약학적 조성물은 탈모 방지 및 발모 개선, 촉진용 피부외용제로서 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 또는 카타플라스마제의 피부 외용제 형태의 약학조성물로 제조하여 사용할 수 있으나, 이에 제한되는 것은 아니다.The L-tetrahydro palmatin is preferably a composition for external application to the skin, and the external pharmaceutical composition for external use containing L-tetrahydro palmatin of the present invention as an active ingredient is a cream as an external preparation for preventing hair loss and improving and promoting hair growth, Gel, patch, spray, ointment, warning agent, lotion, liniment agent, pasta agent or cataplasma can be prepared and used as a pharmaceutical composition for external use on the skin, but is not limited thereto.
본 발명의 L-테트라하이드로팔마틴은 약학적으로 허용 가능한 염의 형태로 사용할 수 있으며, 상기 유기산은, 예를 들면 포름산, 아세트산, 프로피온산, 락트산, 부티르산, 이소부티르산, 트리플, 루오로아세트산, 말산, 말레산, 말론산, 푸마르산, 숙신산, 숙신산 모노아미드, 글루탐산, 타르타르산, 옥살산, 시트르산, 글리콜산, 글루쿠론산, 아스코르브산, 벤조산, 프탈산, 살리실산, 안트라닐산, 디클로로아세트산, 아미노옥시 아세트산, 벤젠술폰산, p-톨루엔술폰산 및 메탄술폰산계 염을 포함하며 무기산은 예를 들면 염산, 브롬산, 황산, 인산, 질산, 탄산 및 붕산계 염을 포함한다. 바람직하게는 염산염 또는 아세트산염 형태일 수 있으며, 보다 바람직하게는 염산염 형태일 수 있다. 상기 언급된 산 부가염은 a) 상기 화학식 1의 화합물 및 산을 직접 혼합하거나, b) 이들 중 한 가지를 용매 또는 함수 용매 중에 용해시키고 혼합시키거나, 또는 c) 화학식 1의 화합물을 용매 또는 수하 용매 중의 산에 위치시키고 이들을 혼합하는 일반적인 염 제조방법으로 제조된다. 위와는 별도로 추가적으로 염이 가능한 형태는 가바염, 가바펜틴염, 프레가발린염, 니코틴산염, 아디페이트염, 헤미말론산염, 시스테인염, 아세틸시스테인염, 메티오닌염, 아르기닌염, 라이신염, 오르니틴염, 아스파르트산염 등이 있다.L-tetrahydro palmatin of the present invention can be used in the form of a pharmaceutically acceptable salt, and the organic acid is, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, triple, luoroacetic acid, malic acid, Maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, dichloroacetic acid, aminooxyacetic acid, benzenesulfonic acid , p-toluenesulfonic acid and methanesulfonic acid salts, and inorganic acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid salts. Preferably, it may be in the form of hydrochloride or acetate, and more preferably in the form of hydrochloride. The above-mentioned acid addition salt can be prepared by a) directly mixing the compound of formula 1 and an acid, b) dissolving one of them in a solvent or a hydrous solvent and mixing, or c) dissolving the compound of formula 1 in a solvent or water. It is prepared by a general method of preparing salts by placing them in an acid in a solvent and mixing them. In addition to the above, additional salts available include gaba salt, gabapentin salt, pregabalin salt, nicotinate salt, adipate salt, hemimalonate, cysteine salt, acetylcysteine salt, methionine salt, arginine salt, lysine salt, ornithine salt, Aspartate, etc.
본 발명에 따른 산 부가염은 통상의 방법, 예를 들면, 상기 L-테트라하이드로팔마틴을 과량의 산 수용액 중에 용해시키고, 이 염을 수혼화성 유기 용매, 예를 들면 메탄올, 에탄올, 아세톤 또는 아세토니트릴을 사용하여 침전시켜서 제조할 수 있다. 동량의 L-테트라하이드로팔마틴 및 물 중의 산 또는 알코올을 가열하고, 이어서 이 혼합물을 증발시켜서 건조시키거나 또는 석출된 염을 흡입 여과시켜 제조할 수도 있다.The acid addition salt according to the present invention is prepared by a conventional method, for example, by dissolving the L-tetrahydropalmatine in an aqueous solution of an excess of acid, and dissolving the salt in a water-miscible organic solvent such as methanol, ethanol, acetone or aceto. It can be prepared by precipitation using nitrile. It can also be prepared by heating equal amounts of L-tetrahydropalmatine and an acid or alcohol in water, followed by evaporating the mixture to dryness, or by suction filtration of the precipitated salt.
또한, 염기를 사용하여 약학적으로 허용 가능한 금속염을 만들 수 있다. 알칼리 금속 또는 알칼리 토금속 염은 예를 들면 화합물을 과량의 알칼리 금속 수산화물 또는 알칼리 토금속 수산화물 용액 중에 용해하고, 비용해 화합물 염을 여과하고, 여액을 증발, 건조시켜 얻는다. 이때, 금속염으로는 나트륨, 칼륨 또는 칼슘염을 제조하는 것이 제약상 적합하다. 또한, 이에 대응하는 은 염은 알칼리 금속 또는 알칼리 토금속 염을 적당한 은염(예, 질산은)과 반응시켜 얻는다.In addition, a pharmaceutically acceptable metal salt may be prepared using a base. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and evaporating and drying the filtrate. In this case, it is pharmaceutically suitable to prepare a sodium, potassium or calcium salt as the metal salt. Also, the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).
또한, 본 발명의 상기 L-테트라하이드로팔마틴은 약학적으로 허용되는 염뿐만 아니라, 통상의 방법에 의해 제조될 수 있는 모든 염, 수화물 및 용매화물을 모두 포함한다.In addition, the L-tetrahydro palmatin of the present invention includes all salts, hydrates and solvates that can be prepared by conventional methods as well as pharmaceutically acceptable salts.
본 발명에 따른 부가염은 통상의 방법으로 제조할 수 있으며, 예를 들면 L-테트라하이드로팔마틴을 수혼화성 유기용매, 예를 들면 아세톤, 메탄올, 에탄올, 또는 아세토니트릴 등에 녹이고 과량의 유기산을 가하거나 무기산의 산 수용액을 가한 후 침전시키거나 결정화시켜서 제조할 수 있다. 이어서 이 혼합물에서 용매나 과량의 산을 증발시킨 후 건조시켜서 부가염을 얻거나 또는 석출된 염을 흡인 여과시켜 제조할 수 있다.The addition salt according to the present invention can be prepared by a conventional method, for example, by dissolving L-tetrahydropalmatine in a water-miscible organic solvent, such as acetone, methanol, ethanol, or acetonitrile, and adding an excess of organic acid. Or it can be prepared by adding an acid aqueous solution of an inorganic acid and then precipitating or crystallizing it. Subsequently, after evaporating the solvent or excess acid from this mixture, it can be dried to obtain an addition salt, or it can be prepared by suction filtration of the precipitated salt.
본 발명의 조성물을 의약품으로 사용하는 경우, L-테트라하이드로팔마틴 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 약학적 조성물은 임상투여 시 에 다양한 하기의 경구 또는 비경구 투여 형태로 제제화되어 투여될 수 있으나, 이에 한정되는 것은 아니다.When the composition of the present invention is used as a pharmaceutical, a pharmaceutical composition containing L-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient is formulated into various oral or parenteral dosage forms during clinical administration. and may be administered, but is not limited thereto.
경구 투여용 제형으로는 예를 들면 정제, 환제, 경/연질 캅셀제, 액제, 현탁제, 유화제, 시럽제, 과립제, 엘릭시르제 등이 있는데, 이들 제형은 유효성분 이외에 희석제(예: 락토즈, 덱스트로즈, 수크로즈, 만니톨, 솔비톨, 셀룰로즈 및/ 또는 글리신), 활택제(예: 실리카, 탈크, 스테아르산 및 그의 마그네슘 또는 칼슘염 및/또는 폴리에틸렌 글리콜)를 함유하고 있다. 정제는 또한 마그네슘 알루미늄 실리케이트, 전분 페이스트, 젤라틴, 메틸셀룰로즈, 나트륨 카복시메틸셀룰로즈 및/또는 폴리비닐피롤리딘과 같은 결합제를 함유할 수 있으며, 경우에 따라 전분, 한천, 알긴산 또는 그의 나트륨 염과 같은 붕해제 또는 비등 혼합물 및/또는 흡수제, 착색제, 향미제, 및 감미제를 함유할 수 있다.Formulations for oral administration include, for example, tablets, pills, hard/soft capsules, solutions, suspensions, emulsifiers, syrups, granules, elixirs, and the like. rose, sucrose, mannitol, sorbitol, cellulose and/or glycine), lubricants (eg silica, talc, stearic acid and its magnesium or calcium salts and/or polyethylene glycol). Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, optionally starch, agar, alginic acid or its sodium salt. disintegrants or effervescent mixtures and/or absorbents, colorants, flavoring agents, and sweetening agents.
본 발명의 L-테트라하이드로팔마틴 또는 이의 약학적으로 허용가능한 염을 유효 성분으로 하는 약학적 조성물은 비경구 투여할 수 있으며, 비경구 투여는 피하주사, 정맥주사, 근육 내 주사 또는 흉부 내 주사를 주입하는 방법에 의한다. 이때, 비경구 투여용 제형으로 제제화하기 위하여 상기 L-테트라하이드로팔마틴 또는 이의 약학적으로 허용 가능한 염을 안정제 또는 완충제와 함께 물에 혼합하여 용액 또는 현탁액으로 제조하고, 이를 앰플 또는 바이알 단위 투여형으로 제조할 수 있다. 상기 조성물은 멸균되고/되거나 방부제, 안정화제, 수화제 또는 유화 촉진제, 삼투압 조절을 위한 염 및/또는 완충제 등의 보조제, 및 기타 치료적으로 유용한 물질을 함유할 수 있으며, 통상적인 방법인 혼합, 과립화 또는 코팅 방법에 따라 제제화할 수 있다.The pharmaceutical composition comprising L-tetrahydro palmatin or a pharmaceutically acceptable salt thereof of the present invention as an active ingredient can be administered parenterally, and parenteral administration is subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. by the injection method. At this time, in order to formulate a formulation for parenteral administration, the L-tetrahydropalmatine or a pharmaceutically acceptable salt thereof is mixed with water together with a stabilizer or buffer to prepare a solution or suspension, and this is an ampoule or vial unit dosage form. can be manufactured with The composition may be sterilized and/or contain adjuvants such as preservatives, stabilizing agents, wetting or emulsifying agents, salts and/or buffers for regulating osmotic pressure, and other therapeutically useful substances, and mixing, granulation, in a conventional manner. It can be formulated according to the method of formulation or coating.
또한, 본 발명의 화합물의 인체에 대한 투여량은 환자의 나이, 몸무게, 성별, 투여형태, 건강상태 및 질환 정도에 따라 달라질 수 있으며, 몸무게가60 ㎏인 성인 환자를 기준으로 할 때, 일반적으로 0.001 ~ 1,000㎎/일이며, 바람직하게는 0.01 ~ 500 ㎎/일이며, 의사 또는 약사의 판단에 따라 일정시간 간격으로 1일 1회 내지 수회로 분할 투여할 수도 있다.In addition, the dosage of the compound of the present invention to the human body may vary depending on the patient's age, weight, sex, dosage form, health status and disease level, and is generally based on an adult patient weighing 60 kg. 0.001 to 1,000 mg/day, preferably 0.01 to 500 mg/day, may be administered in divided doses once or several times a day at regular time intervals according to the judgment of a doctor or pharmacist.
또한, 본 발명은 L-테트라하이드로팔마틴 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 탈모 방지 또는 개선용, 또는 발모 또는 육모 촉진용 의약외품을 제공한다. 상기 L-테트라하이드로팔마틴의 구체적인 내용은 전술한 바와 같다.In addition, the present invention provides a quasi-drug for preventing or improving hair loss, or for promoting hair growth or hair growth, comprising L-tetrahydropalmatine or a pharmaceutically acceptable salt thereof as an active ingredient. Specific details of the L-tetrahydro palmatin are the same as described above.
본 발명의 L-테트라하이드로팔마틴을 의약외품 조성물의 유효성분으로 사용할 경우, 탈모 방지 및 모발성장 촉진 효과를 나타내는 상기 L-테트라하이드로팔마틴을 그대로 첨가하거나, 다른 의약외품 또는 의약외품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합량은 사용 목적에 따라 적합하게 결정될 수 있다.When the L-tetrahydro palmatin of the present invention is used as an active ingredient in the quasi-drug composition, the L-tetrahydro palmatin, which exhibits the effect of preventing hair loss and promoting hair growth, can be added as it is, or it can be used together with other quasi-drugs or quasi-drug ingredients. , may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of use.
본 발명에 따른 L-테트라하이드로팔마틴은 남가새 식물을 통상적으로 사용되는 유기용매를 통한 추출물 및 물을 이용한 수추출, 초임계추출을 통하여 추출할 수 있다. 상기 L-테트라하이드로팔마틴의 추출을 위해 사용되는 추출 용매의 예로는 정제수; 메탄올, 에탄올, 이소프로필알코올, 부탄올 등의 저급 알코올; 글리세롤, 에틸렌 글리콜, 프로필렌 글리콜, 1,3-부틸렌 글리콜 등의 다가 알코올; 그리고 석유에테르, 메틸아세테이트, 에틸아세테이트, 벤젠, 헥산, 메틸렌클로라이드, 디에틸에테르, 디클로로메탄클로로포름 등의 탄화수소계 용매 등을 예로 들 수 있다.L-tetrahydro palmatin according to the present invention can be extracted through water extraction and supercritical extraction using an extract using an organic solvent and water from a namgasae plant. Examples of the extraction solvent used for extraction of the L-tetrahydro palmatin include purified water; lower alcohols such as methanol, ethanol, isopropyl alcohol and butanol; polyhydric alcohols such as glycerol, ethylene glycol, propylene glycol, and 1,3-butylene glycol; and hydrocarbon solvents such as petroleum ether, methyl acetate, ethyl acetate, benzene, hexane, methylene chloride, diethyl ether, and dichloromethane chloroform.
또한 이들 중에서 하나 또는 두 종류 이상의 용매를 혼용할 수 있다.In addition, one or two or more types of solvents may be mixed among them.
이하. 본 발명을 실시예에 의해 상세히 설명한다. 단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다.Below. The present invention will be described in detail by way of Examples. However, the following examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following examples.
참조예 1: L-테트라하이드로팔마틴(L-tetrahydropalmatine) 물질 정보Reference Example 1: L-tetrahydropalmatine (L-tetrahydropalmatine) material information
[화학식 1][Formula 1]
Cas number: 483-14-7Cas number: 483-14-7
구입처: Sigma-aldrich (미국)Where to buy: Sigma-aldrich (USA)
실험예 1: 모유두 세포 증식 촉진 효과Experimental Example 1: Effect of promoting dermal papilla cell proliferation
모유두세포(Dermal papilla cell)는 모낭의 기저에 위치한 중배엽 유래의 섬유아세포로서, 모낭의 모기질 세포와 상호작용을 통해 모발의 성장에서 중요한 역할을 하는 것으로 알려져 있다. 인간 모유두세포(Human dermal papilla cell)는 DMEM(Gibco Inc, NY. USA)배지에 10% heat-inactivated fetal bovine serum (FBS; Gibco Inc. NY. USA)와 100 units/ml penicillin-100 μg/ml streptomycin (Gibco Inc, NY, USA)를 첨가하여 37℃, 5% CO2 항온기에서 배양하였다. 모유두세포의 증식은 MTT assay를 이용하여 측정하였다. 모유두세포를 1 x 104 cells/well 농도로 96 웰플레이트에 분주한 후 24시간 동안 배양하였다. 배양 배지를 제거 후 1% FBS가 포함된 DMEM 배지에 미녹시딜 및 L-테트라하이드로팔마틴을 농도 별로 희석하여 세포에 처리한 후 72시간동안 추가 배양하였다. 72시간 후, 각 웰 당 0.5 mg/ml 농도로 배지에 희석된 MTT 용액 200 μl를 처리하여 3시간 반응시켰다. 생성된 포마잔(formazan)은 DMSO 100 μl로 용해시킨 후 micro-plate reader로 540 nm 에서 흡광도를 측정하여 세포의 생장 정도를 판단하였다. 모유두세포의 증식 촉진 효과는 측정된 흡광도 값으로부터 무처리 대조군 대비 하기 수학식 1에 따라 증식율(%)을 구하고 결과를 표 1에 나타내었다.Dermal papilla cells are mesodermal-derived fibroblasts located at the base of hair follicles, and are known to play an important role in hair growth through interaction with the matrix cells of the hair follicles. Human dermal papilla cells were mixed with 10% heat-inactivated fetal bovine serum (FBS; Gibco Inc. NY. USA) with 100 units/ml penicillin-100 μg/ml in DMEM (Gibco Inc, NY. USA) medium. Streptomycin (Gibco Inc, NY, USA) was added and cultured at 37° C., 5% CO 2 incubator. The proliferation of dermal papilla cells was measured using the MTT assay. The dermal papilla cells were dispensed in a 96-well plate at a concentration of 1 x 10 4 cells/well and then cultured for 24 hours. After removing the culture medium, minoxidil and L-tetrahydro palmatin were diluted by concentration in DMEM medium containing 1% FBS, and the cells were treated and further cultured for 72 hours. After 72 hours, 200 μl of the MTT solution diluted in the medium at a concentration of 0.5 mg/ml per well was treated and reacted for 3 hours. The generated formazan was dissolved in 100 μl of DMSO and the absorbance was measured at 540 nm with a micro-plate reader to determine the degree of cell growth. The proliferation-promoting effect of dermal papilla cells was obtained by calculating the proliferation rate (%) according to Equation 1 below compared to the untreated control group from the measured absorbance values, and the results are shown in Table 1.
[수학식 1][Equation 1]
증식율(%)= (시료 처리군의 흡광도/대조군의 흡광도) x 100Growth rate (%) = (absorbance of sample treatment group / absorbance of control group) x 100
상기 표 1의 결과에서 볼 수 있듯이, L-테트라하이드로팔마틴을 72시간 처리한 배지 조건에서 실험 농도 내 모유두세포 독성은 확인되지 않았으며, 최대 20.09%의 증식 촉진 효과를 나타내었다.As can be seen from the results of Table 1, L-tetrahydro palmatin was not confirmed in the experimental concentration in the medium condition treated for 72 hours, dermal papilla cytotoxicity, it exhibited a proliferation-promoting effect of up to 20.09%.
실험예 2: 5-알파 환원효소 유전자 발현 억제 효과Experimental Example 2: 5-alpha reductase gene expression inhibitory effect
제 1형 및 제 2형 5-알파 환원효소가 있다고 알려진 모유두 세포에서 L-테트라하이드로팔마틴이 효소의 발현을 억제하는 효과가 있는지 quantitative real-time PCR(qRT-PCR) 실험법을 통해 유전자 발현량을 확인하였다. 무혈청배지에 L-테트라하이드로팔마틴과 두타스테라이드를 농도 별로 희석하여 모유두 세포에 72시간 처리한 후, 배양액을 제거하고 easy-spin Total RNA extraction kit (iNtRON biotechology, korea)를 이용하여 세포에서 RNA를 추출하였다. 추출된 RNA는 Nanodrop spectrophotometer (Thermo Scientific, USA)를 이용하여 RNA 양을 측정하였다. 일정량의 RNA를 취한 다음 Maxime RT Premix Oligo dt (iNtRON biotechology, korea)를 사용하여 cDNA를 합성하였다. 유전자의 발현을 측정하기 위하여 power SYBR Green PCR master mix (Applied biosystems, USA)와 각각의 primer 그리고 합성된 cDNA를 이용하여 7500 Fast Real-Time PCR System (Applied Biosystems, USA) 기기에서 반응시켰다. PCR 과정은 40 cycle 수행하였고, 각각의 유전자(GAPDH, 5α-R1, 5α-R2)에 대한 primer 염기서열은 표 4과 같다. 결과는 Excel를 이용하여 분석, 정량 하였으며, 분석법으로는 comparative Ct (threshold cycle) 방법을 이용하였다.Gene expression level by quantitative real-time PCR (qRT-PCR) experiment to determine whether L-tetrahydropalmatine has the effect of inhibiting enzyme expression in dermal papilla cells known to have type 1 and type 2 5-alpha reductase was confirmed. After diluting L-tetrahydro palmatin and dutasteride by concentration in serum-free medium and treating the dermal papilla cells for 72 hours, the culture medium was removed and the cells were extracted from the cells using an easy-spin Total RNA extraction kit (iNtRON biotechology, Korea). RNA was extracted. The extracted RNA was measured for the amount of RNA using a Nanodrop spectrophotometer (Thermo Scientific, USA). After taking a certain amount of RNA, cDNA was synthesized using Maxime RT Premix Oligo dt (iNtRON biotechology, Korea). To measure gene expression, the power SYBR Green PCR master mix (Applied biosystems, USA), each primer, and synthesized cDNA were used for reaction in a 7500 Fast Real-Time PCR System (Applied Biosystems, USA) device. The PCR process was performed for 40 cycles, and the primer sequences for each gene (GAPDH, 5α-R1, 5α-R2) are shown in Table 4. The results were analyzed and quantified using Excel, and the comparative Ct (threshold cycle) method was used as the analysis method.
5-알파 환원 효소 2종 발현 변화를 확인한 결과는 표 2에 나타내었다. L-테트라하이드로팔마틴을 농도 별 처리하였을 때 5-알파 환원효소 활성을 2종 모두 억제시키는 것으로 확인되었다. 5-알파 환원 효소의 발현을 억제하는 것은 탈모를 유발하는 혈중 DHT의 농도를 감소시킬 수 있으므로, 탈모방지 및 발모 촉진 효과를 가질 수 있다.Table 2 shows the results of confirming the expression changes of two types of 5-alpha reductase. When L-tetrahydro palmatin was treated by concentration, it was confirmed that both types of 5-alpha reductase activity were inhibited. Inhibiting the expression of 5-alpha reductase can reduce the concentration of DHT in the blood that causes hair loss, so it can have the effect of preventing hair loss and promoting hair growth.
(ppm)density
(ppm)
mRNA
상대발현량5α-R1
mRNA
Relative expression
mRNA
상대발현량5α-R2
mRNA
Relative expression
감소율
(% 대조군 대비)5α-R1 expression
decrease rate
(% compared to control)
감소율
(% 대조군 대비)5α-R2 expression
decrease rate
(% compared to control)
실험예 3: 테스토스테론으로 유도된 DHT 생합성 억제 효과Experimental Example 3: Inhibitory effect of testosterone-induced DHT biosynthesis
모유두 세포에서 테스토스테론 처리로 유도된 DHT 생합성량을 DHT ELISA kit (MyBiosource, San Diego, CA, USA)를 이용하여 정량하였다. 무혈청배지에 테스토스테론 100 μM과 L-테트라하이드로팔마틴 및 두타스테라이드를 농도 별로 희석한 뒤 모유두 세포에 72시간 동시 처리한 후, 배양액을 취하여 DHT ELISA kit로 DHT 생합성 정도를 측정하였다. DHT 생합성 정도는 테스토스테론 처리 대조군에 대한 상대적인 합성능으로 감소율을 계산하고 결과를 표 3에 나타내었다.The amount of DHT biosynthesis induced by testosterone treatment in dermal papilla cells was quantified using a DHT ELISA kit (MyBiosource, San Diego, CA, USA). After diluting 100 μM of testosterone, L-tetrahydropalmatine and dutasteride by concentration in serum-free medium, and simultaneously treating the dermal papilla cells for 72 hours, the culture medium was taken and the degree of DHT biosynthesis was measured with a DHT ELISA kit. The degree of DHT biosynthesis was calculated as a rate of decrease relative to the testosterone-treated control group, and the results are shown in Table 3.
(% 테스토스테론 처리군(T) 대비)DHT biosynthesis reduction rate
(% compared to testosterone treatment group (T))
상기 표 3의 결과에서 볼 수 있듯이, L-테트라하이드로팔마틴은 테스토스테론으로 유도된 DHT 생합성을 최대 28.78% 억제하였으며, 이는 5-알파 환원 효소의 활성을 저해함에 따라 DHT 생합성능을 억제시킨 것임을 알 수 있다. 이 결과로부터, 본 발명에 따른 조성물은 탈모를 유발하는 혈중 DHT 농도를 효과적으로 감소시켜 탈모방지 및 발모 촉진 효과를 가지는 것을 알 수 있다.As can be seen from the results in Table 3, L-tetrahydro palmatin inhibited testosterone-induced DHT biosynthesis by up to 28.78%, which inhibited the DHT biosynthesis performance by inhibiting the activity of 5-alpha reductase. can From this result, it can be seen that the composition according to the present invention effectively reduces the concentration of DHT in the blood that causes hair loss, thereby preventing hair loss and promoting hair growth.
R: TCCACCACCCTGTTGCTGTAF: ACCACAGTCCATGCCATCAC
R: TCCACCACCCTGTTGCTGTA
R: GGCATAGCCACACCACTCCATGAF: ACCACAGTCCATGCCATCAC
R: GGCATAGCCACACCACTCCATGA
R: CCGTGTGCTTCCCGTAGCCGF: AACACGGCGCGATGCAGGGTT
R: CCGTGTGCTTCCCGTAGCCG
이상의 결과를 종합하여 보면, L-테트라하이드로팔마틴을 포함하는 조성물은 모유두 세포 증식 효과, 5-알파 환원효소 활성 저해 효과 및 DHT 생성 억제효과를 나타내어 우수한 탈모 완화 효과를 나타냄을 알 수 있다.Taken together, it can be seen that the composition containing L-tetrahydro palmatin exhibits an excellent hair loss alleviation effect by exhibiting a dermal papilla cell proliferation effect, an inhibitory effect on 5-alpha reductase activity and an effect on DHT production.
하기에 본 발명의 L-테트라하이드로팔마틴을 포함하는 각종 형태의 모발 및 두피 적용 조성물 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, formulation examples of various types of hair and scalp application compositions containing L-tetrahydro palmatin of the present invention will be described, but the present invention is not intended to limit the present invention, but merely to describe them in detail.
Claims (6)
상기 L-테트라하이드로팔마틴의 함량은 상기 조성물의 0.0001~10중량%인 탈모방지 또는 발모 촉진용 조성물.According to claim 1,
The content of the L-tetrahydro palmatin is 0.0001 to 10% by weight of the composition for preventing hair loss or promoting hair growth.
상기 조성물은 용액, 현탁액, 유탁액, 페이스트, 로션, 파우더, 비누, 계면활성제함유 클린싱 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션, 샴푸, 린스, 토닉 및 스프레이로 구성된 군으로부터 선택되는 제형을 갖는 탈모방지 또는 발모 촉진용 화장료 조성물.4. The method of claim 3,
The composition has a formulation selected from the group consisting of solutions, suspensions, emulsions, pastes, lotions, powders, soaps, cleansing oils containing surfactants, powder foundations, emulsion foundations, wax foundations, shampoos, rinses, tonics and sprays. A cosmetic composition for preventing hair loss or promoting hair growth.
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The Alkaloids: Chemistry and Biology, Vol.68, pp83-156, 2010. 1부.* * |
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