KR20180094305A - Composition for preventing alopecia and promoting hair growth containing a glycoprotein derived from Ophiopogon japonicus - Google Patents
Composition for preventing alopecia and promoting hair growth containing a glycoprotein derived from Ophiopogon japonicus Download PDFInfo
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- KR20180094305A KR20180094305A KR1020170020451A KR20170020451A KR20180094305A KR 20180094305 A KR20180094305 A KR 20180094305A KR 1020170020451 A KR1020170020451 A KR 1020170020451A KR 20170020451 A KR20170020451 A KR 20170020451A KR 20180094305 A KR20180094305 A KR 20180094305A
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- South Korea
- Prior art keywords
- composition
- protein polysaccharide
- hair
- molecular weight
- polysaccharide
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Abstract
Description
본 발명은 탈모방지 또는 발모촉진용 조성물에 관한 것으로서, 구체적으로는 맥문동(Ophiopogon japonicus) 유래의 저분자 단백다당체를 유효성분으로 포함함으로써 모유두 세포의 성장을 촉진시키고, 외부 자극으로부터 각질형성세포를 보호함으로써 모발의 생장과 건강한 두피 생육을 촉진시킬 수 있는 탈모방지 또는 발모촉진용 조성물에 관한 것이다.The present invention relates to a composition for preventing hair loss or promoting hair growth, and more specifically, it relates to a composition for promoting growth of hair dermal papilla cells by containing a low molecular weight protein polysaccharide derived from Ophiopogon japonicus as an active ingredient and protecting keratinocytes from external stimuli To a composition for preventing hair loss or promoting hair growth, which can promote hair growth and healthy scalp growth.
탈모의 원인에 관하여서는 모근, 피지선 등의 기관에서 남성 호르몬의 작용설, 모낭(Hair follicle)의 혈류량 저하, 세균 번식이나 피지 분비 과다에 의한 두피 이상설, 유전적 요인 그리고 노화 등이 거론되어 왔다. 그러나 아직까지 탈모에 대한 명확한 원인은 규명되고 있지 않으며, 최근 들어 오히려 탈모증으로 고민하는 사람이 점점 늘고 있고 그 연령층도 낮아지고 있는 실정이다.The causes of hair loss have been discussed in male or female organs such as hair follicle, hair follicle, hair follicle, bacterial growth, sebaceous secretion, genetic factors and aging. However, the definite cause of hair loss has not yet been clarified. Recently, more and more people are suffering from alopecia, and the age group is lowering.
탈모증의 치료법에 관해서도 아직까지 뚜렷한 효과를 지닌 것은 없으며, 동의보감에는 국화산, 삼성고 및 자영산 등 탈모에 관계되는 몇몇 복용하는 처방들이 기재되어 있고, 호마유(참깨) 등을 탈모 부위에 마사지한다든지, 특정 한약처방을 주침(酒沈)해서 바르는 방법과 특정 혈위를 자극하는 방법 등이 기재되어 있다. 그러나 이들 방법은 효과에 있어서 개인적 차이가 많다고 알려져 있으며, 일반적으로 적용될 수 있는 신약 소재는 아직까지 보고되지 않고 있다.There are no clear effects on the treatment of alopecia. There are some prescriptions for taking hair loss, such as Chung Hwa Mountain, Samsung High and Jae Young Mountain, How to apply a prescribed herbal remedy and how to stimulate a specific herb. However, these methods are known to have a large effect on individual differences in effectiveness, and no new drug materials that can be generally applied have been reported yet.
인체의 모발은 약 100만개 이상이고, 특히 두발은 10만개 이상이며, 이들 모발은 생장기(anagen), 퇴행기(catagen), 휴지기(telogen)의 3단계 주기를 거치고 각각의 모발은 독립적인 주기로 활동하며 진행된다. 탈모는 머리카락이나 털이 어떤 원인에 의하여 정상보다 적거나 없는 상태를 의미하는데, 크게 모발이 휴지기 상태에서 빠지는 일반적인 탈모 현상인 휴지기 탈모(telogen effluvium)과 비정상적인 탈모 현상인 생장기 탈모 현상(anagen effluvium)으로 구별할 수 있으며, 후자를 일반적으로 탈모라 일컫는다. 탈모(또는 탈모 질환)는 형태, 증상 또는 원인 등에 따라, 원형 탈모증(Alopecia Areata), 유전성 안드로겐 탈모증(Androgenetic Alopecia), 휴지기 탈모증(Telogen Effluvium), 외상성 발모벽(Trichoti lomania), 압박성(Pressure Alopecia) 등의 생장기 탈모증, 비강성, 매독성(Alopecia syphlltiac), 지루 탈모증(Alopecia seborrhecia), 증후성, 반흔성, 선천성 탈모증 등으로 분류되고 있다.The human body has more than one million hairs, especially over 100,000 hairs. These hairs undergo a three-stage cycle of anagen, catagen, and telogen, and each hair acts in an independent cycle It proceeds. Hair loss refers to a condition in which hair or hair is less or no more than normal due to any cause. The hair loss is distinguished by telogen effluvium, which is a general hair loss phenomenon in which hair comes out from resting state, and anagen effluvium, which is abnormal hair loss phenomenon And the latter is generally referred to as hair loss. Alopecia Areata, Androgenetic Alopecia, Telogen Effluvium, Trichoti lomania, Pressure Alopecia (Alopecia Areata), Alopecia Areata (Alopecia Areata), Telogen Effluvium, ), Alopecia syphiltiac, Alopecia seborrhecia, symptomatic, scarring, congenital alopecia, and the like.
종래의 탈모증 치료방법으로는, 호르몬설과 관련하여 여성 호르몬을 주재로 한 제제가 있으나, 효과뿐 아니라 피부 염증 발생, 호르몬 투여에 의한 부작용 발생 등의 보고가 있어 현재는 사용이 중단되고 있다. 발모제로서 미국 업존사의 미녹시딜(minoxidil), 이태리 크리노스(Crinos, Co.)사의 트리코사카라이드 (trichosaccharide) 등을 주성분으로 하는 제제가 사용되고 있으나, 뚜렷한 효과의 부재 및 부작용 문제가 대두되고 있다. 또한 머크사에서 개발한 피나스테라이드(finasteride)는 모낭에서 남성호르몬 테스토스테론 대사에 작용하는 효소인 5-α-리덕테이즈(5-α-reductase)의 활성을 억제시키는 물질로 알려져 있으나, 우울증을 유발할 수 있으며 이 또한 장기간의 치료가 필요하다는 문제점을 안고 있다. 이 외에도 크레시나와 로게인이 있지만, 탈모 질환이 완전히 진행되기 전인 정상 두피에 모근이 살아있는 경우에만 사용된다. 이처럼 종래의 여러 종류의 발모제는 일반적으로 두피의 혈행 촉진과 모근의 영양공급을 목적으로 하여 모발의 성장에 도움을 주도록 하는 방법이 시도되었으나, 이 역시 독성과 부작용이 심하고, 그 효과 또한 미흡한 것이 현재 실정이다.As a conventional method for treating alopecia, there is a preparation based on female hormone in relation to hormonal theory, but its use is being discontinued due to reports of skin inflammation and adverse effects caused by hormone administration. As a hair growth agent, there is used a preparation mainly composed of minoxidil of US-based company and trichosaccharide of Crinos Co., Ltd. However, there is a problem of lack of clear effect and side effects. In addition, finasteride, developed by Merck, is known to inhibit the activity of 5-α-reductase, an enzyme that acts on the male hormone testosterone metabolism in hair follicles, And this also has the problem that long-term treatment is necessary. In addition, there are Crescina and Rogaine, but only when the hair follicle is alive on the normal scalp before the hair loss disease is fully progressed. As described above, various conventional hair growth promoting methods have generally been attempted to promote hair growth with the aim of stimulating blood circulation and supplying nutrients to hair follicles. However, this method also has a serious toxicity and side effect, It is true.
본 발명자들은 합성 화학물질에 비해 안전성이 확보된 천연물을 대상으로 탈모방지 및 발모촉진 기능을 갖는 조성물을 개발하기 위하여, 다양한 연구를 수행하였다. 그 결과, 맥문동( Ophiopogon japonicus) 유래의 단백다당체, 특히 저분자량 단백다당체가 사람의 모유두 세포(Dermal papilla cell)를 산화스트레스로부터 보호하고 자외선에 의한 자극으로부터 사람의 각질형성세포(Human keratinocyte)를 보호, 염증을 억제하는 활성을 지니고 있어 모발의 생장 및 건강한 두피 생육을 촉진시킴으로써 탈모의 진행을 완화시키고, 모발의 양모/육모 그리고 두피를 보호하는 활성을 가진다는 것을 발견하였다.The present inventors have conducted various studies to develop a composition having a function of preventing hair loss and accelerating hair growth in natural products having safety compared to synthetic chemicals. As a result, maekmundong (Ophiopogon japonicus , especially low-molecular-weight protein polysaccharides, protects human dermal papilla cells from oxidative stress, protects human keratinocytes from stimulation by ultraviolet rays, and inhibits inflammation To promote the growth of hair and healthy scalp growth, thereby alleviating the progress of hair loss, and having the activity of protecting hair / hair growth and scalp of hair.
따라서 본 발명은 맥문동 유래의 단백다당체를 유효성분으로 포함하는, 탈모방지 또는 발모촉진용 조성물을 제공하는 것을 목적으로 한다.Accordingly, it is an object of the present invention to provide a composition for preventing hair loss or promoting hair growth, which comprises a macrolide-derived protein polysaccharide as an active ingredient.
본 발명은 맥문동 유래의 단백다당체를 유효성분으로 포함하는, 탈모방지 또는 발모촉진용 조성물이 제공된다.The present invention provides a composition for preventing hair loss or for promoting hair growth, comprising a macromolecular-derived protein polysaccharide as an active ingredient.
본 발명자들은 연구를 통해, 맥문동 유래의 단백다당체, 특히 저분자량 단백다당체가 사람의 모유두 세포(Dermal papilla cell)를 산화스트레스로부터 보호하고 자외선에 의한 자극으로부터 사람의 각질형성세포(Human keratinocyte)의 보호 및 염증억제 활성을 가짐으로써 모발의 생장 및 건강한 두피 생육을 촉진할 수 있다는 것을 밝혀내었다. 따라서 본 발명에 따른 맥문동 유래의 단백다당체는 탈모의 진행을 완화시키고, 모발의 양모/육모, 성장을 촉진하는 조성물, 즉 탈모방지 또는 발모촉진용 약학 조성물 혹은 기능성 화장료 조성물에 유용하게 사용될 수 있다.The inventors of the present invention have found through research that the macronectin-derived protein polysaccharide, particularly the low molecular weight protein polysaccharide, protects human dermal papilla cells from oxidative stress and protects human keratinocytes from stimulation by ultraviolet light And inflammation-inhibiting activity, thereby promoting hair growth and healthy scalp growth. Therefore, the protein polysaccharide derived from the macromuscular gland according to the present invention can be usefully used in a composition for alleviating the progress of hair loss and promoting hair wool / hair growth and growth, that is, a pharmaceutical composition for preventing hair loss or promoting hair growth or a functional cosmetic composition.
도 1은 맥문동 저분자량 단백다당체의 구성당 분석 HPLC 크로마토그램이다.
도 2는 맥문동 저분자량 단백다당체의 분자량 분석 GPC 결과를 나타낸다.
도 3은 맥문동 유래의 단백다당체 및 단백다당체 분획을 사람의 모유두 세포(HHDPC)에 처리하였을 때 산화스트레스 보호 효과 중 세포생존율을 측정한 결과를 나타낸다.
도 4는 실시예 2의 단백다당체 분획을 사람의 모유두 세포(HHDPC)에 처리하였을 때, 형광 현미경을 통하여 촬영한 세포 사진이다.
도 5는 맥문동 유래의 단백다당체 및 단백다당체 분획을 사람의 모유두 세포(HHDPC)에 처리하였을 때 산화스트레스 보호 효과 중 대조군 대비 ROS 생성율(%)을 측정한 결과를 나타낸다.
도 6은 맥문동 유래의 단백다당체 및 단백다당체 분획의 염증억제 효능(NO 억제율)을 측정한 결과를 나타낸다.
도 7은 맥문동 유래의 단백다당체를 C57BL/6 마우스에 처리하였을 때 조직학적 변화를 관찰한 결과를 나타낸다.
도 8은 맥문동 유래의 단백다당체를 C57BL/6 마우스에 처리하였을 때 모발 생장 촉진 효과를 측정한 결과를 나타낸다.BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a constitutional analytical HPLC chromatogram of the macromolecular low molecular weight protein polysaccharide.
Figure 2 shows the molecular weight analysis GPC results of the low molecular weight protein polysaccharide.
FIG. 3 shows the results of measuring the cell survival rate during the oxidative stress protection effect when the protein polysaccharide and the protein polysaccharide fraction derived from the McDonald's were treated with human dermal papilla cells (HHDPC).
FIG. 4 is a photograph of a cell taken by fluorescence microscope when the protein polysaccharide fraction of Example 2 was treated with human dermal papilla cells (HHDPC). FIG.
FIG. 5 shows the results of measurement of ROS production ratio (%) of the oxidative stress-protecting effect against human dermal papilla cells (HHDPC) when the protein polysaccharide and protein polysaccharide fractions derived from the McGuire were treated.
Fig. 6 shows the results of measurement of the inflammation-inhibiting effect (NO inhibition rate) of the protein polysaccharide and the protein polysaccharide fraction derived from the mulberry root.
FIG. 7 shows the results of observing histological changes when C57BL / 6 mice were treated with the macronutrient-derived protein polysaccharide.
FIG. 8 shows the results of measuring the hair growth promoting effect when treating the macronutrient-derived protein polysaccharide with C57BL / 6 mice.
본 발명은 맥문동( Ophiopogon japonicus) 유래의 단백다당체를 유효성분으로 포함하는, 탈모방지 또는 발모촉진용 조성물을 제공한다.The invention maekmundong (Ophiopogon The present invention provides a composition for preventing hair loss or for promoting hair growth, which comprises a protein polysaccharide derived from a plant of the genus Japonicus as an active ingredient.
맥문동은 외떡잎식물 백합목 백합과의 여러해살이풀로, 한방에서는 뿌리를 약재로 사용하며, 예로부터 염증, 열병, 진액부족의 증상 등의 치료제로 널리 사용되어왔다. 맥문동 추출물의 항산화, 항균효과, 혈관이완효과 등이 있음이 보고되었고, 특히 최근에는 맥문동의 스피카토사이드(Spicatoside) A, B 등 사포닌의 구조가 확인되었으며, 항염증, 암세포 억제 작용 등이 있음이 보고되고 있다.Macmun dong is a perennial herb that has been used as a medicinal herb in oriental medicine and has been widely used as a remedy for inflammation, fever and symptoms of lack of juice. Antimicrobial effect and vasorelaxant effect of extract of mungummundong have been reported. Especially recently, the structure of saponin such as spicatoside A and B of mungmun dong has been confirmed, and it has been reported that anti-inflammation, .
그러나, 현재까지 맥문동 유래의 단백다당체를 사용한 세포 생물학적 효능에 대한 실험 연구 결과가 미비하며, 맥문동 유래의 단백다당체를 이용한 기능성 식품 및 화장품 또는 의약품 등의 개발 또한 미비한 실정이다.However, the results of experimental studies on the cell biologic efficacy using the macromolecular-derived protein polysaccharide to date have been lacking, and the development of functional foods, cosmetics, or pharmaceuticals using the macromolecular-derived protein polysaccharide is insufficient.
본 발명에서 사용되는 맥문동 유래의 단백다당체는 사람의 모유두 세포(Dermal papilla cell)의 성장을 촉진시키고, 산화스트레스 및 자외선에 의한 자극으로부터 사람의 모유두 세포 및 사람의 각질형성세포(Human keratinocyte)를 보호하는 활성을 지니고 있어 모발의 생장 및 건강한 두피 생육을 촉진시킬 수 있으므로, 궁극적으로 탈모의 진행을 완화시키고, 모발의 양모/육모 그리고 성장을 촉진시킬 수 있다. 따라서, 맥문동 유래의 단백다당체는 탈모방지 또는 발모촉진용 약학 조성물 혹은 기능성 화장료 조성물에 있어서 유효성분으로서 유용하게 사용될 수 있다.The macronutrient-derived protein polysaccharide used in the present invention promotes the growth of human dermal papilla cells and protects human dermal papilla cells and human keratinocytes from oxidative stress and stimulation by ultraviolet rays So that hair growth and healthy scalp growth can be promoted, thereby ultimately alleviating the progress of hair loss, and promoting hair wool / hair growth and hair growth. Therefore, the protein polysaccharide originated from the macromolecule can be usefully used as an effective ingredient in a pharmaceutical composition for preventing hair loss or promoting hair growth or a functional cosmetic composition.
본 발명에서 탈모(또는 탈모 질환)는 원형 탈모증(Alopecia Areata), 유전성 안드로겐 탈모증(Androgenetic Alopecia), 휴지기 탈모증(Telogen Effluvium), 외상성, 발모벽(Trichoti lomania), 압박성(Pressure Alopecia) 등의 생장기 탈모증, 비강성, 매독성(Alopecia syphlltiac), 지루 탈모증(Alopecia seborrhecia), 증후성, 반흔성, 선천성 탈모증 등을 포함한다.In the present invention, hair loss (or hair loss disease) is caused by alopecia areata, androgenetic alopecia, telogen effluvium, traumatic, Trichotillomania, pressure alopecia, Alopecia, alopecia syphiltiac, Alopecia seborrhecia, symptomatic, scarring, congenital alopecia, and the like.
본 발명에 따른 조성물에 있어서, 맥문동 유래의 단백다당체는 맥문동의 열수 추출물로부터 유래한 분획물일 수 있으며, 하기의 단계를 포함하는 방법으로 제조될 수 있다:In the composition according to the present invention, the protein polysaccharide originated from the macromolecule can be a fraction derived from the hot-water extract of macromuscularum, and can be produced by a method including the following steps:
a) 용매에 맥문동을 첨가한 다음, 원심분리를 통해 저분자량의 폴리페놀을 제거하는 단계,a) adding a molten copper to the solvent, removing the low molecular weight polyphenol by centrifugation,
b) 상기 a) 단계에서 폴리페놀을 제거하여 얻은 맥문동 잔사로부터 수용성 활성성분을 추출한 다음, 필터프레스 여과 및 농축하여 농축액을 얻는 단계, 및b) extracting the water-soluble active ingredient from the ginseng residue obtained by removing the polyphenol in step a), followed by filtering and concentrating the filter press to obtain a concentrated liquid; and
c) 상기 b) 단계에서 얻은 농축액으로부터 알코올 침전 반응 후, 필터프레스 적용하여 알코올이 제거된 맥문동 단백다당체를 분리하는 단계.c) separating alcohol-removed macromolecular protein polysaccharide by applying a filter press after alcohol precipitation reaction from the concentrate obtained in step b).
또한, 본 발명은, d) 상기 c) 단계에서 얻은 맥문동 단백다당체로부터 한외여과 실시하여 분자량 별로 분리하는 단계를 추가로 포함할 수 있다.Further, the present invention may further comprise: d) performing ultrafiltration from the marshmallow gelatinized protein polysaccharide obtained in step c), and separating the microorganism by the molecular weight.
하기에서 맥문동 단백다당체를 제조하는 방법을 각 단계별로 구체적으로 설명한다.Hereinafter, a method for producing a macromolecular protein polysaccharide will be described in detail for each step.
a) 용매에 맥문동을 첨가한 다음, 원심분리를 통해 저분자량의 폴리페놀을 제거하는 단계.a) adding a molten copper to the solvent, and then removing the low molecular weight polyphenol by centrifugation.
맥문동에서 저분자량의 폴리페놀을 제거하기 위해서 용매 추출 방법을 사용한다. 이 때, 맥문동은 건조된 상태로 사용함이 바람직하며, 제거 효율을 높이기 위하여 절단된 상태, 바람직하게는 분말화된 상태, 보다 바람직하게는 d50이 100 ~ 1000㎛의 범위인 분말 상태로 사용한다.A solvent extraction method is used to remove low molecular weight polyphenols from McMundan. At this time, it is preferable to use the cornflower in a dried state, and it is used in a state of being cut, preferably in a powdered state, more preferably a powder having a d50 of 100 to 1000 탆 in order to increase the removal efficiency.
본 단계에서 용매로는 헥산, 에탄올 및 메탄올로 이루어진 군에서 선택된 1종 이상을 사용하는 것이 바람직하며, 화장료 적용시 잔존량으로 야기될 수 있는 독성 문제를 방지하기 위해서 에탄올을 사용하는 것이 보다 바람직하다.At this stage, it is preferable to use at least one selected from the group consisting of hexane, ethanol and methanol, and it is more preferable to use ethanol in order to prevent the toxicity problem caused by the residual amount when applying the cosmetic .
맥문동에 상기 용매를 첨가하고 상온에서 6시간 내지 10시간, 바람직하게는 7 내지 9시간 동안 충분히 교반한 후, 저분자량의 폴리페놀은 상등액에 존재하고 맥문동 원물만 침전시킬 수 있도록 5000 rpm 내지 7000 rpm, 바람직하게는 5500~6500rpm으로, 15분 내지 45분, 바람직하게는 25분 내지 35분 동안 원심분리를 수행하며, 이를 통해 저분자량의 폴리페놀이 용해되어 있는 용매를 제거한다. 이 때, 저분자량의 폴리페놀은 순수한 단백다당체를 확보하기 위해 제거하는 것으로서, 원하는 단백다당체에 비하여 분자량이 더 작은 것을 말하며, 구체적으로는 분자량이 1000달톤 이하인 폴리페놀을 말한다. 얻어진 맥문동 잔사를 건조하면 폴리페놀이 함유되지 않은 맥문동을 얻을 수 있다.After the solvent is added to the gangmongdong and the mixture is sufficiently stirred at room temperature for 6 hours to 10 hours, preferably 7 to 9 hours, the low molecular weight polyphenol is dissolved in the supernatant liquid at 5000 rpm to 7000 rpm , Preferably 5500 to 6500 rpm, for 15 minutes to 45 minutes, preferably 25 minutes to 35 minutes, thereby removing the solvent in which the low molecular weight polyphenol is dissolved. At this time, the low molecular weight polyphenol is removed to secure a pure protein polysaccharide, which means a smaller molecular weight than a desired protein polysaccharide, and specifically refers to a polyphenol having a molecular weight of 1,000 Da or less. Drying of the residue obtained by the above method can obtain a polyphenol free macromolecule.
b) 상기 a) 단계에서 폴리페놀을 제거하여 얻은 맥문동 잔사로부터 수용성 활성성분을 추출한 다음, 필터프레스 여과 및 농축하여 농축액을 얻는 단계.b) extracting a water-soluble active ingredient from the ginseng residue obtained by removing the polyphenol in the step a), and then filtering and concentrating the product by filtration to obtain a concentrated liquid.
상기 a) 단계에서 얻은 맥문동 잔사로부터 활성성분을 추출한다. 활성성분을 추출하기 위하여, 용매로는 물, 탄소수 1 내지 4의 무수 또는 함수 저급 알코올을 사용하며, 바람직하게는 물, 보다 바람직하게는 온수를 사용하여 수용성 활성성분을 추출한다. 특히, 본 발명에 있어서 온수 추출은 30~40℃의 온도에서 수행하는 것이 바람직하다. 이는 40℃ 초과시 고온으로 인하여 최종적으로 얻고자 하는 단백다당체에 열변성이 생길 수 있으며, 30℃ 미만일 경우는 단백다당체가 충분히 추출되지 않기 때문이다. 또한, 온수 추출 시간은 6~8시간이 바람직하다. 이는 8시간 초과시 미생물에 의한 오염이 발생할 수 있고, 6시간 미만이면 단백다당체가 충분히 추출되지 않기 때문이다. 얻어진 추출액은 필터프레스를 이용하여 여과한 후 감압 농축하여, 맥문동의 추출물, 특히 온수 추출물의 농축액을 얻는다.The active ingredient is extracted from the ginseng residue obtained in step a). In order to extract the active ingredient, water, an anhydrous or hydro-lower alcohol having 1 to 4 carbon atoms is used as a solvent, and water-soluble active ingredients are preferably extracted using water, more preferably hot water. Particularly, in the present invention, the hot water extraction is preferably carried out at a temperature of 30 to 40 캜. This is because when the temperature is higher than 40 ° C, heat denaturation may occur in the protein polysaccharide ultimately obtained, and when the temperature is lower than 30 ° C, the protein polysaccharide is not sufficiently extracted. The hot water extraction time is preferably 6 to 8 hours. This is because microbial contamination may occur when the time exceeds 8 hours, and the protein polysaccharide is not sufficiently extracted after 6 hours. The obtained extract is filtered using a filter press, and then concentrated under reduced pressure to obtain a concentrated liquid of extracts of MacMyung Dong, especially hot water extract.
c) 상기 b) 단계에서 얻은 농축액으로부터 알코올 침전 반응 후, 필터프레스 적용하여 알코올이 제거된 맥문동 단백다당체를 분리하는 단계.c) separating alcohol-removed macromolecular protein polysaccharide by applying a filter press after alcohol precipitation reaction from the concentrate obtained in step b).
상기 b) 단계에서 얻은 추출물, 특히 열수 추출물의 농축액에서 단백다당체만을 분리하기 위해서 알코올 침전 반응을 수행한다. 상기 농축액에 알코올을 서서히 가해 알코올 침전 반응을 진행한다. 이때, 알코올의 첨가 속도는 100~200ml/min이 바람직하고, 200ml/min를 초과하면 최종 생성 입자의 크기가 너무 커지거나 뭉칠 수 있다. 이때 알코올로는 탄소수 1 내지 4의 무수 또는 함수 저급 알코올, 바람직하게는 에탄올 또는 메탄올을 사용할 수 있으며, 보다 바람직하게는 에탄올을 사용할 수 있다. 사용하는 알코올의 양은 상기 농축액의 10 내지 20배 양을 사용할 수 있다.An alcohol precipitation reaction is carried out in order to separate only the protein polysaccharide from the extract obtained in the step b), especially the concentrated hot water extract. Alcohol is gradually added to the concentrate to conduct an alcohol precipitation reaction. At this time, the rate of addition of alcohol is preferably 100 to 200 ml / min, and if it exceeds 200 ml / min, the size of the final produced particles may become too large or coagulate. The alcohol may be an anhydrous or a lower alcohol having 1 to 4 carbon atoms, preferably ethanol or methanol, more preferably ethanol. The amount of alcohol used may be 10 to 20 times the amount of the concentrate.
알코올 침전 반응이 완료되면 필터프레스 적용하여 알코올을 제거하고, 얻어진 맥문동 단백다당체를 40~50℃에서 진공 건조함으로써, 파우더 형태의 맥문동 단백다당체를 얻을 수 있다. 단백다당체는 다당류(polysaccharide) 부분이 약 50~80 중량% 존재하며, 단백질(protein) 부분이 약 10~40중량% 존재한다. 이 두 부분이 아미노산-당(amino acid-sugar) 결합에 의하여 연결되어 있다. 본 발명에 따른 맥문동 단백다당체의 분자량은 1천 내지 1만 달톤(dalton)이다. After the alcohol precipitation reaction is completed, a filter press is applied to remove the alcohol, and the resultant macromolecular protein polysaccharide is vacuum dried at 40 to 50 ° C to obtain a powdery macromorphic protein polysaccharide. The protein polysaccharide has about 50 to 80% by weight of the polysaccharide portion and about 10 to 40% by weight of the protein portion. These two parts are connected by an amino acid-sugar bond. The molecular weight of the macromolecular protein polysaccharide according to the present invention is from 1,000 to 10,000 daltons.
d) 상기 c) 단계에서 얻은 맥문동 단백다당체로부터 한외여과 실시하여 분자량 별로 분리하는 단계.d) performing ultrafiltration from the marshmallow gelatinized protein polysaccharide obtained in the step c) to isolate it by molecular weight.
상기 c) 단계에서 얻은 맥문동 단백다당체는 대략 1천 내지 1만 달톤(dalton)의 분자량을 갖고 있는데, 한외여과를 수행함으로써 맥문동 단백다당체를 분자량 별로 분리할 수 있다. 이때 한외여과에 적용하기 위해 맥문동 단백다당체를 녹이는 용매로는 물을 사용하는 것이 바람직하며, 한외여과를 이용하여 맥문동 단백다당체를 분자량이 1천 이상 3천 미만(저분자량 맥문동 단백다당체), 3천 이상 5천 미만(중분자량 맥문동 단백다당체), 5천 이상(고분자량 맥문동 단백다당체)인 것을 포함하는 분획으로 분리하는 것이 바람직하다. 한외여과는 연속식 공정으로서 저분자량 물질의 분리 및 여과액의 농축을 동시에 진행할 수 있을 뿐만 아니라, 공정이 상온에서 이루어지기 때문에 열변성의 문제가 발생하지 않는다는 장점을 갖는다.The macromolecular protein polysaccharide obtained in the step c) has a molecular weight of about 1,000 to 10,000 daltons. By performing ultrafiltration, the macromolecular protein polysaccharide can be separated by molecular weight. In this case, it is preferable to use water as a solvent for dissolving the macromolecular protein polysaccharide for ultrafiltration. Ultrafiltration can be used to dissolve the macromolecular protein polysaccharide in a molecular weight of 1,000 to less than 3,000 (low molecular weight macromolecular protein polysaccharide) , More than 5,000 (medium molecular weight paraffin waxy protein polysaccharide), and 5,000 or more (high molecular weight paraffin waxy protein polysaccharide). Ultrafiltration is a continuous process that not only can the separation of low molecular weight substances and the concentration of the filtrate proceed at the same time but also has the advantage that the problem of heat deformation does not occur because the process is carried out at room temperature.
본 발명에 있어서, 상기 맥문동 단백다당체에서 당 성분은 글루코스(glucose), 갈락토스(galactose), 만노스(mannose), 푸코스(fucose), N-아세틸갈락토사민(N-Acetylgalactosamine), N-아세틸글루코사민(N-Acetylglucosamine), N-아세틸뉴라민산(N-Acetylneuraminic acid), 자일로스(xylose), 람노스(rhamnose), 아라비노스(arabinose), 프럭토스(fructose)로 이루어진 군에서 선택되는 1종 이상을 함유할 수 있다.In the present invention, the saccharide component of the macromolecular complex protein polysaccharide is glucose, galactose, mannose, fucose, N-acetylgalactosamine, N-acetylglucosamine A compound selected from the group consisting of N-acetylglucosamine, N-acetylneuraminic acid, xylose, rhamnose, arabinose, and fructose. Or more.
바람직하게, 상기 맥문동 단백다당체의 주요 구성 당은 하기 화학식 1로 표시되는 글루코스일 수 있다.Preferably, the major constituent sugar of the macromolecular protein polysaccharide may be glucose represented by the following formula (1).
본 발명의 조성물에 유효성분으로 포함되는 상기 맥문동 단백다당체의 함량은 조성물 전체 중량에 대하여, 0.001 내지 50중량%이다. 0.001중량% 미만이면 효과적인 효능 전달이 미약하고, 50중량% 초과이면 제제 중에서 다른 원료와의 상용성 문제가 발생하기 때문에 바람직하지 않다. The content of the macromolecular protein polysaccharide contained as an active ingredient in the composition of the present invention is preferably in the range of, 0.001 to 50% by weight. If the amount is less than 0.001% by weight, effective delivery of the effective amount is insufficient. If the amount is more than 50% by weight, compatibility problems with other raw materials may occur.
본 발명의 조성물은 상기한 맥문동 유래의 단백다당체 및 약학적으로 허용가능한 담체를 포함하는 약학 조성물 형태일 수 있다. 상기 약학 조성물은 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제제, 외용제, 및 멸균 주사용액의 형태로 제제화될 수 있다. 상기 약학적으로 허용 가능한 담체는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 포함한다. 또한, 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 포함한다. 경구용 고형 제제는 정제, 환제, 산제, 과립제, 캡슐제 등을 포함하며, 이러한 고형 제제는 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 포함할 수 있으며, 마그네슘 스테아레이트, 탈크 같은 윤활제 등을 포함할 수 있다. 경구용 액상 제제는 현탁제, 내용액제, 유제, 시럽제 등을 포함하며, 물, 리퀴드 파라핀 등의 희석제, 습윤제, 감미제, 방향제, 보존제 등을 포함할 수 있다. 비경구용 제제는 멸균된 수용액, 비수성용제, 현탁제, 유제를 포함하며, 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르류 등을 포함한다.The composition of the present invention may be in the form of a pharmaceutical composition comprising the above-mentioned macromolecular-derived protein polysaccharide and a pharmaceutically acceptable carrier. The pharmaceutical composition may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral preparations such as syrups and aerosols, external preparations and sterilized injection solutions according to a conventional method. The pharmaceutically acceptable carrier may be selected from the group consisting of lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. It also includes diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, and the like. Solid form preparations for oral use include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like, and may include lubricants such as magnesium stearate and talc. Oral liquid preparations include suspensions, solutions, emulsions, syrups, and the like, and may contain diluents such as water and liquid paraffin, wetting agents, sweetening agents, fragrances, preservatives and the like. The parenteral preparation may be a sterile aqueous solution, a non-aqueous solution, a suspending agent, or an emulsion, and may be a non-aqueous solution, a suspen- sive agent such as propylene glycol, polyethylene glycol, vegetable oil such as olive oil, And the like.
약학 조성물에 함유되는 맥문동 유래의 단백다당체의 투여량은 환자의 상태 및 체중, 질병의 정도, 약물 형태, 투여 경로 및 기간에 따라 다르지만, 경우에 따라 적절하게 선택될 수 있다. 예를 들면, 상기 맥문동 유래의 단백다당체는 1일 0.0001 내지 100mg/kg으로, 바람직하게는 0.01 내지 100mg/kg의 용량이 되도록 약학 조성물의 제형으로 투여될 수 있으며, 상기 투여는 하루에 한번 또는 수회 나누어 이루어질 수도 있다. 상기 약학 조성물은 인간 등의 포유동물에 다양한 경로로, 예를 들면, 경구, 정맥, 근육, 또는 피하 주사에 의해 투여될 수 있다.The macromolecule contained in the pharmaceutical composition The dosage of the resulting protein polysaccharide varies depending on the condition and the weight of the patient, the degree of disease, the drug form, the administration route and the period, but may be suitably selected depending on the case. For example, Derived protein polysaccharide may be administered in the form of a pharmaceutical composition at a daily dose of 0.0001 to 100 mg / kg, preferably 0.01 to 100 mg / kg, and the administration may be performed once or several times a day. The pharmaceutical compositions may be administered to mammals, such as humans, by a variety of routes, for example, by oral, intravenous, intramuscular, or subcutaneous injection.
본 발명의 조성물은 상기 맥문동 유래의 단백다당체를 유효성분으로 포함하는 피부 외용제 조성물, 구체적으로는 화장료 조성물 또는 약학 조성물, 바람직하게는 기능성 화장료 조성물 형태일 수 있다. 상기 피부 외용제 조성물은 상기 맥문동 유래의 단백다당체를 사용하여 통상의 피부 외용제 조성물의 제조방법에 따라, 다양한 형태로 제조될 수 있다. 예를 들어, 상기 피부 외용제 조성물은 상기 맥문동 유래의 단백다당체를 함유하는 향장 제품, 샴푸, 헤어 토닉, 헤어 로션, 헤어 크림, 헤어 젤, 모발 영양화장수, 연고 등의 형태로 제조될 수 있으며, 이는 통상의 클렌징액, 수렴액 및 보습액으로 희석하여 사용될 수 있다. 또한, 상기 화장료 조성물은 화장료 조성물 분야에서 통상적으로 사용되는 안정화제, 용해화제, 비타민, 안료, 및 향료와 같은 통상적인 보조제를 포함할 수 있다.The composition of the present invention can be applied to the above- Derived protein polysaccharide as an active ingredient, specifically a cosmetic composition or a pharmaceutical composition, preferably a functional cosmetic composition. The composition for external application for skin comprises the above- Derived protein polysaccharide according to a conventional method for producing a composition for external application for skin. For example, the composition for external application for skin may be manufactured in the form of a perfume product containing the polysaccharide derived from the macromolecule, a shampoo, a hair tonic, a hair lotion, a hair cream, a hair gel, a hair lotion, an ointment, It can be diluted with a normal cleansing liquid, a converging liquid, and a moisturizing liquid. The cosmetic composition may also contain conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments, and flavorings commonly used in the cosmetic composition arts.
이하, 본 발명을 실시예, 참고예 및 시험예를 통하여 더욱 상세히 설명한다. 그러나 이들 실시예 및 시험예는 본 발명을 예시하기 위한 것으로, 본 발명의 범위가 이들에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail by way of examples, reference examples and test examples. However, these examples and test examples are for illustrating the present invention, and the scope of the present invention is not limited thereto.
[실시예 1] 맥문동 단백다당체의 제조 [Example 1] Preparation of macromolecular protein polysaccharide
건조 맥문동(충남 청양군)을 분쇄하고 체질 및 분급 처리하여 제조된 맥문동 분말(d50=100 ~ 1000㎛) 10kg을 95%(v/v) 에탄올 150리터에 분산하고 상온에서 약 8시간 동안 교반하였다. 제조된 혼합액을 약 5000rpm으로 약 30분 동안 원심분리하여(원심분리시 사용된 기기: High-speed Centrifuge 2236R, Labogene), 맥문동 단백다당체보다 분자량이 작은 저분자량의 폴리페놀이 제거된 맥문동 잔사를 회수하였다. 회수된 잔사는 상기 용매 추출 공정을 1회 반복한 후에 건조하였다.10 kg of McMundum powder (d50 = 100-1000 mu m) prepared by pulverizing, sifting and classifying dry macromuscularum (Cheongyang, Chungnam) was dispersed in 150 liters of 95% (v / v) ethanol and stirred at room temperature for about 8 hours. The prepared mixture was centrifuged at about 5000 rpm for about 30 minutes (high-speed Centrifuge 2236R, Labogene), and a low molecular weight polyphenol having a smaller molecular weight than the macromolecular protein polysaccharide was recovered Respectively. The recovered residue was dried once after repeating the solvent extraction step once.
상기 용매 추출 공정으로 저분자량 폴리페놀을 제거한 맥문동 분말에 물 125리터를 첨가하고 35℃에서 7시간 동안 교반하여 열수 추출을 진행하였다. 얻어진 맥문동 단백다당체 추출액은 필터프레스기기(서파산업, 규격 : 400mm, 16ch)를 이용하여 여과 및 회수한 후, 초기 부피의 1/10이 되도록 50℃에서 감압 농축하였다.125 liters of water was added to the Mukmun-dong powder from which the low molecular weight polyphenol was removed by the solvent extraction process, and the mixture was stirred at 35 ° C for 7 hours to conduct hot water extraction. The obtained extract of Mokdongdong protein polysaccharide was filtered and recovered using a filter press machine (Sawa Industry, standard: 400mm, 16ch), and then concentrated under reduced pressure at 50 ° C to 1/10 of the initial volume.
상기 맥문동의 열수 추출물 농축액의 10배 부피의 에탄올을 100ml/min의 속도로 서서히 가해 에탄올 침전반응을 진행했다. 침전된 맥문동 단백다당체를 필터프레스기기(서파산업, 규격 : 400mm, 16ch)를 이용하여 여과 및 회수한 후, 45℃에서 진공 건조하여 파우더 형태의 맥문동 단백다당체 2.5kg(수평균 분자량: 3.2kDa)을 얻었다. The ethanol precipitation reaction was carried out by gradually adding ethanol at a rate of 100 ml / min, which was 10 times the volume of the concentrated hot-water extract concentrate of McMundum-dong. The precipitated macromolecular protein polysaccharide was filtered and recovered by using a filter press machine (Sawa Industry, standard: 400 mm, 16 ch), and vacuum dried at 45 캜 to obtain 2.5 kg (number average molecular weight: 3.2 kDa) ≪ / RTI >
[실시예 2 ~ 4] 맥문동 분자량 별 단백다당체의 제조 [Examples 2 to 4] Preparation of protein polysaccharide by molecular weight
실시예 1 맥문동 단백다당체를 10%중량의 농도로 물에 녹여 한외여과에 적용하였으며 Stirred cell 8400에 Ultra PL RC 1K membrane, 3K membrane, 5K membrane, 10K membrane을 상온에서 적용하여 맥문동 단백다당체를 분자량이 1천 이상 3천 미만, 3천 이상 5천 미만, 5천 이상인 것을 포함하는 분획으로 분리하였다. 각 분획을 45℃에서 진공 건조하여 파우더 형태의 분자량 별 맥문동 단백다당체 분획 시료를 확보하였으며 분자량이 1천 이상 3천 미만인 분획 시료를 저분자량 맥문동 단백다당체(실시예 2), 3천 이상 5천 미만인 분획 시료를 중분자량 맥문동 단백다당체(실시예 3), 5천 이상인 분획 시료를 고분자량 맥문동 단백다당체(실시예 4)로 구분하였다. 각 시료의 수득량 및 수득율은 표 1에 제시된 바와 같다.Example 1 The macromolecular protein polysaccharide was dissolved in water at a concentration of 10% by weight and applied to ultrafiltration. Ultra Polycarbonate 1K membrane, 3K membrane, 5K membrane and 10K membrane were applied to Stirred cell 8400 at room temperature. 1 to 3,000, 3,000 to 5,000, and 5,000 or more. Each fraction was vacuum-dried at 45 ° C to obtain a fractionated macromolecular protein polysaccharide fraction sample by the molecular weight of the powder form. A fraction sample having a molecular weight of 1,000 to less than 3,000 was classified into a low molecular weight macromolecular protein polysaccharide (Example 2) A fractionated sample was classified into a medium molecular weight paraffin waxy protein polysaccharide (Example 3) and a 5,000 or more fraction sample was classified into a high molecular weight paraffin waxy protein polysaccharide (Example 4). The yield and the yield of each sample are as shown in Table 1.
[참고예 1] 맥문동 단백다당체 및 분자량별 단백다당체 분획의 화학적 특성 분석[Reference Example 1] Chemical characterization of macromolecular protein polysaccharide and protein polysaccharide fraction by molecular weight
1) 단백질 함량 분석1) Analysis of protein content
조성물의 단백질 함량을 측정하기 위해 BCA(bicinchoninic acid) 측정법을 수행하였다. BCA 측정법은 단백질이 구리 이온(Cu2 +, Cu1 +)을 환원시킬 수 있는 성질을 이용한 것으로 단백질에 의해 환원된 구리 이온은 BCA 용액과 반응하여 보라빛의 화합물(Cu+/BCAchromophore)을 생성하게 되는데, 이 보랏빛 화합물은 특정 파장 562㎚에서 최대 흡광도를 보인다. 따라서 단백질의 양이 많을수록 보랏빛 화합물이 더 많이 생기며 562㎚에서 흡광도가 증가함을 이용하여 단백질의 양을 측정하였다. 실험방법은 하기와 같다.A bicinchoninic acid (BCA) assay was performed to determine the protein content of the composition. The BCA assay uses the property that proteins can reduce copper ions (Cu 2 + , Cu 1 + ). Copper ions reduced by the protein react with BCA solution to produce a violet compound (Cu + / BCAchromophore) This violet compound shows the maximum absorbance at a specific wavelength of 562 nm. Therefore, the amount of protein was measured by increasing the absorbance at 562 nm as the amount of protein was increased. The experimental method is as follows.
우선 마이크로 BCA 단백질 측정 시약 키트(Pierce, cat. no. 23227)를 이용, 각 96마이크로플레이트 웰에 각각 150㎕씩 표준액 또는 희석된 시료를 넣은 후 BCA(bicinchoninic acid) 키트 WR(Working Reagent) 시약을 첨가하여 30초간 격렬히 혼합하였다. 그 후 37℃, 2시간 동안 반응시키고 마이크로플레이트 판독기(UVT-06685, Thermo max, 미국)로 540㎚ 흡광도를 측정하여 검량선을 작성하고 단백질 정량하였다. 단백질 함량 분석 결과는 표 2에 제시된 바와 같다.First, 150 μl of the standard solution or diluted sample was added to each well of 96 microplate using a micro BCA protein measurement reagent kit (Pierce, Cat. No. 23227), and then BCA (bicinchoninic acid) kit WR (Working Reagent) reagent And mixed vigorously for 30 seconds. Then, the reaction was carried out at 37 ° C for 2 hours, and a 540 nm absorbance was measured with a microplate reader (UVT-06685, Thermo max, USA) to prepare a calibration curve and quantify the protein. The results of protein content analysis are shown in Table 2.
2) 총 당 함량 분석2) Analysis of total sugar content
맥문동 단백다당체 및 분자량별 단백다당체 분획의 당 함량은 페놀-황산법으로 측정하였다. 0.1mg/ml의 농도로 실시예 1 내지 실시예 4를 증류수에 용해시킨 용액 50μl에 5% 페놀용액 50μl와 진한 황산 200μl을 가하고 혼합한 후, 상온에서 20분간 반응시켜 490nm에서 흡광도를 측정하였다. 표준품으로 글루코스를 사용하여 검량선을 작성하였다. 당 함량 분석 결과는 표 3에 제시된 바와 같다.Sugar content of macromolecular protein polysaccharide and protein polysaccharide fraction by molecular weight was measured by phenol - sulfuric acid method. 50 μl of a 5% phenol solution and 200 μl of concentrated sulfuric acid were added to and mixed with 50 μl of a solution prepared by dissolving the compounds of Examples 1 to 4 in distilled water at a concentration of 0.1 mg / ml. The mixture was reacted at room temperature for 20 minutes and absorbance was measured at 490 nm. Calibration curves were prepared using glucose as a standard. The results of the sugar content analysis are shown in Table 3.
3) 맥문동 단백다당체 및 분자량 별 단백다당체 분획의 구성 당 분석3) Composition analysis of macromolecular protein polysaccharide and protein polysaccharide fraction by molecular weight
맥문동 단백다당체 및 분자량별 단백다당체 분획 2.5㎎을 1㎖의 3차 증류수에 용해한 후 TFA(trifluoroacetic acid)를 이용하여 가수분해시켰다. 그 후 PMP(1-phenyl-3-methyl-5-pyrazolone)를 이용하여 유도체화(derivatization)한 다음 Shim-pack(6.0x150mm, CLC-ODS) 컬럼과 고압 액체크로마토그래피(Agilent Technologies 1200 Series HPLC, Agilent, 미국)를 이용하여 UV 245㎚에서 검출하였으며 표준물질로 1mM 혼합물(Man, GlcU, Rha, Ara, Gal, Glc, Xyl, Fuc)을 사용하여 검량선을 작성하고 본 발명의 맥문동 단백다당체 폴리머의 당 성분을 확인한 후 그 결과를 하기 표 4에 나타내었다.2.5 mg of the macromolecular protein polysaccharide and the protein polysaccharide fraction by molecular weight were dissolved in 1 ml of tertiary distilled water and hydrolyzed with TFA (trifluoroacetic acid). The mixture was then derivatized using PMP (1-phenyl-3-methyl-5-pyrazolone) and purified by Shim-pack (6.0x150mm, CLC-ODS) and high pressure liquid chromatography (Agilent Technologies 1200 Series HPLC, (Man, GlcU, Rha, Ara, Gal, Glc, Xyl, and Fuc) as a reference material, and a calibration curve was prepared using the 1mM mixture of the macromolecular protein polysaccharide polymer of the present invention The results are shown in Table 4 below.
함량(ppm)Per constitution
Content (ppm)
4) 맥문동 4) Macmun Dong 단백다당체Protein polysaccharide 및 맥문동 And McMundong 단백다당체Protein polysaccharide 분획의 분자량 분석 Molecular weight analysis of fractions
시료를 각각 젤 투과 크로마토그래피를 이용하여 분자량을 분석하였다. 젤 투과 크로마토그래피는 PL 아쿠아겔 OH-MIXED(8.5 ×400 ㎜, VARIAN, 미국) 컬럼과 고압액체크로마토그래피(Agilent Technologies 1200 Series HPLC/GPC, Agilent, 미국), ELSD(Evaporative Light Scattering Detectors) 검출기(ELSD 3300, Alltech, 미국)를 이용하여 이동상 이온제거수, 컬럼 온도 25℃, 분당 0.7㎖유속, 검출기 온도 50℃, 질소가스 유속 1.4L/min의 조건으로 검출하였으며, HPLC 측정 결과는 도 1에, GPC 츨정 결과는 도 2에 나타내었다. 표준물질로는 각 분자량별 PEG(폴리에틸렌글리콜)를 사용하여 시료의 컬럼 내 지연시간에 따른 분자량의 검량선을 작성하여 실시예 1 내지 4의 수평균 분자량 분포를 표 5에 나타내었다.Each sample was analyzed for molecular weight using gel permeation chromatography. Gel permeation chromatography was performed on a PL aquagel OH-MIXED (8.5 x 400 mm, VARIAN, USA) column and high pressure liquid chromatography (Agilent Technologies 1200 Series HPLC / GPC, Agilent, USA), Evaporative Light Scattering Detectors (ELSD) The results of the HPLC measurement are shown in FIG. 1, and the results are shown in FIG. 1 (a). , And GPC determination results are shown in Fig. Table 5 shows the number average molecular weight distributions of Examples 1 to 4 by preparing a calibration curve of the molecular weight according to the delay time in the column of the sample using PEG (polyethylene glycol) for each molecular weight as a reference material.
[[ 시험예Test Example 1] 맥문동 1] 단백다당체Protein polysaccharide 및 분자량별 분획이 사람의 And molecular weight fraction 모유두세포Dermal papilla cells (Dermal papilla cell) (Dermal papilla cell) 산화스트레스에Oxidative Stress 대한 보호효능 평가 Evaluation of protective efficacy against
모유두세포는 모낭의 기저부에 존재하는 세포로, 모낭을 구성하는 세포들에게 산소와 영양을 공급하여 모발의 성장과 모낭 주기 조절을 담당한다. 따라서 모유두세포의 증식이 촉진되면 모발이 건강해지고 모발 성장이 촉진되며 탈모를 막을 수 있다. 모발의 성장은 모유두(dermal papilla)를 둘러싸고 있는 상피세포(epithelialcell)가 분열하여 모간(hair shaft)을 만들면서 진행되기 때문에 모유두세포는 상피세포의 분열을 조절하는 중요한 역할을 한다. 또한 남성형 탈모증에서 남성호르몬이 모낭에 작용하는 부위 역시 모유두로서 모유두세포는 발모에 있어 매우 중요한 역할을 하고 있다. The dermal papilla cells are the cells located at the base of the hair follicle. They supply oxygen and nutrients to the cells constituting the hair follicle, and control hair growth and follicle cycle regulation. Therefore, when the growth of the dermal papilla cells is promoted, the hair becomes healthy, hair growth is promoted, and hair loss can be prevented. The growth of hair progresses as the epithelial cells surrounding the dermal papilla divide and form the hair shaft, so the dermal papilla cells play an important role in controlling the division of the epithelial cells. In addition, in male alopecia, the region where the male hormone acts on the hair follicle also plays a very important role in hair growth.
모발은 지속적인 생장을 위해 왕성한 세포 분열이 필요하며 이에 따라 산화스트레스가 심한 기관이다. 따라서, 산화스트레스로부터 모발 모유두세포를 보호할 수 있는 조성물은 탈모방지에 효과적으로 작용할 것으로 예상하여 조성물이 모발 모유듀세포를 산화 스트레스로부터 보호할 수 있는지 평가하였다.Hair requires vigorous cell division for sustained growth and is thus an organ with a high level of oxidative stress. Thus, a composition capable of protecting hair dermal papilla cells from oxidative stress was expected to work effectively in preventing hair loss, and evaluated whether the composition could protect hair dermal dermal cells from oxidative stress.
1) 세포 생존율 보호1) Protection of cell survival rate
모유두세포를 96웰에 5,000개 접종하여 24시간 배양 후 소태아혈청이 없는 DMEM 배지에서 48시간 시료 처리하였다. 실시예 1 내지 4를 농도별로 처리하고 과산화수소 1mM을 2.5시간 처리한 다음, 세척 후 소태아혈청이 없는 DMEM 배지에서 24시간 배양하고, WST-1로 생존율을 측정하여 하기 표 6 및 도 3에 그 결과를 나타내었다.The dermal papilla cells were inoculated in 96 wells for 5, 000 hours, cultured for 24 hours, and then treated for 48 hours in DMEM medium without fetal bovine serum. Examples 1 to 4 were treated for each concentration and 1 mM of hydrogen peroxide was treated for 2.5 hours. After washing, the cells were cultured in DMEM medium without fetal bovine serum for 24 hours and the survival rate was measured by WST-1. The results are shown.
상기 표 6 및 도 3에서와 같이, 본 발명에 따른 실시예 1 내지 4는 산화스트레스로부터 모유두세포 보호 효능이 뛰어남을 확인하였으며, 특히 실시예 2 가 산화스트레스로부터 모유두세포 보호 효능이 뛰어남을 확인하였다.As shown in Table 6 and FIG. 3, Examples 1 to 4 according to the present invention were found to be excellent in protecting papillary cells from oxidative stress, and in particular, Example 2 was found to be excellent in protecting papillary cells from oxidative stress .
2) ROS 생성 억제능2) inhibition of ROS formation
UVB에 의해 발생되는 세포 내 활성산소종(ROS) 수준 및 본 발명에 따른 맥문동 단백다당체 및 분자량별 단백다당체 분획의 세포보호 작용을 DCF-DA(dichlorodihydrofluorescein diacetate, Sigma) 방법을 이용하여 평가하였다(Rosenkranz et al., 1992). 각질형성세포를 96-웰 플레이트에 1.0×104 세포수/mL의 밀도로 씨딩하고 37℃에서 24시간 동안 배양하였다. 다음으로, 상기 세포들에 실시예 1 내지 4를 농도별로 처리하였다. 양성대조군으로는 Trolox(Sigma)를 사용하였다(50ppm). 37℃에서 24시간 동안 배양시킨 후, PBS 완충액을 이용하여 행구었다. 이후 DCF-DA 용액(50μM)을 각 웰에 첨가하고 세포들을 어두운 곳에서 40분 동안 두었다. DCF-DA 용액을 HBSS 완충액으로 행구었다. HBSS 완충액을 100μl 가한 후 세포를 UVB 방사선(30 mJ/cm2) 또는 과산화수소(Hydrogen peroxide, sigma) 100μM으로 처치하였다. 이후 형광도 리더기로(Tecan) 상기 플레이트의 형광을 측정하였다(Excutatuib: 485nm, Emission: 535nm). 이 때 비교를 위하여, 어떠한 실험 물질(실시예 1 내지 4, 또는 Trolox) 및 과산화수소를 처리하지 않은 군(무처리군), 및 실험 물질은 처리하지 않고 과산화수소 100μM을 처리한 군에 대한 형광을 측정하였다. 형광 현미경(Thermo)을 통하여 세포의 사진을 촬영하였으며, 이 때 실시예 2와 과산화수소 100μM을 처리한 세포를 촬영한 사진을 도 4에 나타내었다.The cytoprotective activity of the intracellular reactive oxygen species (ROS) levels produced by UVB and the proteolytic polysaccharide fractions of the macromolecular protein polysaccharide and the molecular weight according to the present invention were evaluated using a DCD-DA (dichlorodihydrofluorescein diacetate, Sigma) method (Rosenkranz et al., 1992). The keratinocytes were seeded in a 96-well plate at a density of 1.0 x 10 4 cells / mL and cultured at 37 ° C for 24 hours. Next, Examples 1 to 4 were treated with the concentrations on the cells. Trolox (Sigma) was used as a positive control (50 ppm). After incubation at 37 ° C for 24 hours, the cells were treated with PBS buffer solution. DCF-DA solution (50 μM) was then added to each well and the cells were left in the dark for 40 minutes. The DCF-DA solution was run with HBSS buffer. After 100 μl of HBSS buffer was added, the cells were treated with UVB radiation (30 mJ / cm 2 ) or 100 μM hydrogen peroxide (Sigma). The fluorescence of the plate was then measured by a fluorescence reader (Tecan) (Excutatuib: 485 nm, Emission: 535 nm). For comparison, fluorescence was measured for a group treated with 100 μM of hydrogen peroxide without any experiment materials (Examples 1 to 4, or Trolox) and groups not treated with hydrogen peroxide (no treatment group) Respectively. Cells were photographed through a fluorescence microscope (Thermo), and a photograph of cells treated with Example 2 and 100 μM of hydrogen peroxide was shown in FIG.
형광도 리더기로 측정한 형광값을 통하여 ROS의 상대적인 생성 정도를 구할 수 있는데, 즉 하기 수학식 1에 따라서 과산화수소만 처리한 음성대조군의 형광값을 ROS 생성율 100%로 하고, 실시예 1 내지 4와 H2O2를 처리한 세포(실험군)에 대한 형광값을 음성대조군의 형광값에 대한 상대적인 값으로 나타내었다.The fluorescence value of the negative control group treated with only hydrogen peroxide according to the following
또한, ROS 억제율(%)은 과산화수소만 처리한 음성대조군(100%)과의 차이로 구하였다. 결과는 하기 표 7 및 도 5에 나타내었다.In addition, the ROS inhibition rate (%) was calculated by the difference from the negative control (100%) treated with only hydrogen peroxide. The results are shown in Table 7 and FIG.
+ H2O2 Example 1
+ H 2 O 2
+ H2O2 Example 2
+ H 2 O 2
+ H2O2 Example 3
+ H 2 O 2
+ H2O2 Example 4
+ H 2 O 2
상기 표 7 및 도 5에서와 같이, 본 발명에 따른 실시예 1 내지 4는 ROS의 생성을 억제하는 효능이 뛰어남을 확인하였으며, 특히 실시예 2 가 ROS의 생성 억제 효능이 뛰어남을 확인하였다.As shown in Table 7 and FIG. 5, it was confirmed that Examples 1 to 4 according to the present invention are excellent in inhibiting the production of ROS, and in particular, Example 2 is excellent in inhibiting ROS production.
[[ 시험예Test Example 2] 다양한 맥문동 2] Various gates 단백다당체Protein polysaccharide 및 분자량 분획의 대식세포(RAW cell)에 대한 염증억제 효능 평가 And the molecular weight fraction of RAW cells
항염 효과를 확인하기 위하여, 쥐의 대식세포인 RAW264.7 세포를 ATCC에서 구입하여 이용하였다. 세포의 배양(Cell culture)에 사용된 DMEM/F12(Dulbecco's modified Eagle's medium/ Nutrient Mixture Ham's F12), FBS(fetal bovine serum), L-글루타민, 페니실린-스트렙토마이신 및 인슐린(Insulin)은 Gibco/BRL(USA)에서 구입하였다. 상기 RAW264.7 세포는 DMEM 배지에 10% FBS, 1% 페니실린 스트렙토마이신 1% L-글루타민 및 20㎍/㎖ 인슐린을 첨가한 배양액을 사용하여 배양하였고, 37℃ 습윤한 CO₂배양기(5% CO₂/95% air)에서 배양하였다. 상기 세포가 배양접시의 약 80%가 차게 배양된 후, PBS(pH 7.4)로 세포의 단층을 씻어낸 후 세척하고, 0.25% 트립신 및 2.56mmol/L EDTA를 처리하여 계대 배양하였다.To confirm the anti-inflammatory effect, rat macrophages RAW264.7 cells were purchased from ATCC. (Dulbecco's modified Eagle's medium / Nutrient Mixture Ham's F12), FBS (fetal bovine serum), L-glutamine, penicillin-streptomycin and insulin used for cell culture were purchased from Gibco / BRL USA). The RAW 264.7 cells were cultured in DMEM medium supplemented with 10% FBS, 1
실시예 1 내지 4 각각과 LPS(lipopolysaccharide; 미생물의 세포내독소, 염증유발 물질) 250ng/ml을 함께 첨가한 후, 24시간 배양한 뒤, 상기 24시간 배양한 후의 배양액을 수집하여, NO의 분비량을 Griess reagent system(Promega, USA)을 이용하여 측정하였다. 상기 Griess reagent system을 이용한 측정법은 보다 상세하게는 상기 시스템의 제조사인 Promega에서 제공한 실험방법(protocol)에 의하였고, 상기 수집된 세포배양액에 설파닐아미드 용액을 먼저 넣고, NED 용액을 넣은 후에, 마이크로플레이트 판독기를 이용하여 540nm에서 흡광도를 측정하였다. 이 때, 비교를 위하여 어떠한 실험 물질(실시예 1 내지 4) 및 LPS를 처리하지 않은 군(무처리군), 및 실험 물질은 처리하지 않고 LPS 250ng/ml을 처리한 군에 대한 흡광도를 측정하였다. 하기 수학식 2에 따라서 LPS만 처리한 음성대조군의 흡광도를 NO 생성율 100%로 하고, 실시예 1 내지 4와 LPS를 처리한 세포(실험군)에 대한 흡광도를 음성대조군의 흡광도에 대한 상대적인 값으로 나타내었다.250 ng / ml of LPS (lipopolysaccharide; intracellular toxin, inflammation inducing substance) was added together with each of Examples 1 to 4, followed by culturing for 24 hours. After culturing for 24 hours, the culture solution was collected, Were measured using a Griess reagent system (Promega, USA). The method using the Griess reagent system was described in more detail in the protocol provided by Promega, the manufacturer of the system. After the sulfanilamide solution was added to the collected cell culture solution and the NED solution was added thereto, Absorbance was measured at 540 nm using a microplate reader. At this time, the absorbance was measured for a group treated with 250 ng / ml of LPS without any test substance (Examples 1 to 4), the group not treated with LPS (no treatment group), and the test substance . The absorbance of the negative control group treated with LPS alone according to the following equation (2) was defined as 100% of the NO production rate, and the absorbances of the cells treated with Examples 1 to 4 and LPS (experimental group) were shown relative to the absorbance of the negative control group .
또한, NO 억제율(%)은 LPS만 처리한 음성대조군(100%)과의 차이로 구하였다. 결과를 하기 표 8 및 도 6에 나타내었다.The percent inhibition of NO was determined by the difference from the negative control (100%) treated with LPS only. The results are shown in Table 8 and FIG.
상기 표 8 및 도 6에서와 같이, 본 발명에 따른 실시예 1 내지 4는 염증 생성과 관련된 NO의 생성을 억제하는 효능이 있음을 확인하였으며, 특히 실시예 4가 NO 생성 억제 효능이 뛰어남을 확인하였다.As shown in Table 8 and FIG. 6, it was confirmed that Examples 1 to 4 according to the present invention have an inhibitory effect on the production of NO associated with inflammation production, and in particular, Example 4 shows that NO production inhibitory effect is excellent Respectively.
[[ 시험예Test Example 3] 다양한 맥문동 3] Various manga Dong 단백다당체Protein polysaccharide 및 분자량 분획의 사람 각질형성세포( And human keratinocytes in the molecular weight fraction ( HaCaTHaCaT cell)에 대한 자외선으로 유도된 염증인자 억제 효능 UV-induced inhibition of inflammatory factors
본 발명에 따른 조성물의 자외선에 의한 염증 사이토카인 생성 억제효능을 확인하기 위해, 인간 각질형성세포(HaCaT cells)를 96웰 플레이트에 1×105 cells/ml가 되도록 분주하여 37℃, 5% CO2 인큐베이터에서 16시간 배양한 다음, 본 발명의 실시예 1 내지 4를 각각 농도별로 첨가하였다. 24시간 후 UV-B를 24mJ/cm 조사한 다음 37℃에서 48시간 동안 배양하였으며 배양액을 수거하여 ELISA 분석을 수행하였다.Human keratinocyte (HaCaT cells) were dispensed in a 96-well plate at a density of 1 x 10 5 cells / ml, and incubated at 37 ° C in 5% CO 2 2 incubator for 16 hours, and then Examples 1 to 4 of the present invention were added for each concentration. After 24 hours, UV-B was irradiated at 24 mJ / cm 2 and then cultured at 37 ° C for 48 hours. The culture solution was collected and analyzed by ELISA.
TNF-α, IL-6 및 IL-8은 알앤디 시스템(R&D system)사의 ELISA 키트를 사용하였으며, 회사의 매뉴얼에 따라 실험하였다. 측정 결과는 하기 표 9에 나타내었다.TNF-α, IL-6 and IL-8 were used in an ELISA kit from R & D system and were tested according to the company's manual. The measurement results are shown in Table 9 below.
상기 표 9에서와 같이, 본 발명에 따른 실시예 1 내지 4는 자외선에 의해 유도된 염증 인자인 TNF-α, IL-6 및 IL-8의 발현을 억제하는 효능이 있음을 확인하였으며, 특히 실시예 4가 TNF-α의 발현을 효과적으로 억제하고, 실시예 2가 IL-6의 발현을 효과적으로 억제함 확인하였다.As shown in Table 9, Examples 1 to 4 according to the present invention were found to be effective in inhibiting the expression of TNF-α, IL-6 and IL-8, which are inflammatory factors induced by ultraviolet light, Example 4 effectively inhibited the expression of TNF-a, and Example 2 effectively inhibited the expression of IL-6.
[시험예 4] 맥문동 유래의 저분자량 단백다당체에 의한 C57BL/6 마우스에서의 모발 생장 효과 평가[Test Example 4] Evaluation of hair growth effect in C57BL / 6 mice by low molecular weight protein polysaccharide derived from McDonald
6주령의 C57BL/6 마우스 30마리를 실험에 사용하였고, 마우스를 6마리씩 5그룹으로 나누었다. 마우스는 6마리씩 폴리술폰 케이지에서 사육하였으며, 마우스용 사료와 물은 자유로이 공급하였다. 사육실 환경은 다음과 같은 조건으로 유지하였다: 온도 22±2℃; 습도 50±20%; 환기방식 및 회수 10회/hr; 조명시간 및 명암주기 12hr/day/night; 조도 150~300lux. 동물실험은 을지대학교 동물실험윤리위원회의 승인 [EUIACUC 16-19] 후에 “실험동물 사육 관리의 규정”에 따라 실험하였다. 사료 및 음수 섭취량 및 체중은 주 1회 측정하였다.30 C57BL / 6 mice at 6 weeks of age were used in the experiment, and mice were divided into 5 groups of 6 mice each. The mice were housed in a polysulfone cage with 6 mice, and feeds and water for mice were freely supplied. The breeding environment was maintained under the following conditions: temperature 22 ± 2 ° C;
탈모방지 및 육모효과를 살펴보기 위하여, 등쪽 피부색이 분홍색을 보이는 휴지기 체모의 6주령을 사용하였다. 제모는 전기 동물용 클리퍼와 면도기를 이용하여 조심스럽게 마우스의 등판의 털을 깎아 내어 제거한 후, 탈모제를 이용하며 남아있는 털을 제거하였다. 그 부위에 붓을 이용하여 150μl의 시료를 각 군별로 매일 도포하였다. 시료의 처리는 매일 오전 10시에 3주간 실시하였다.To examine hair loss prevention and hair growth effect, 6-week-old resting hairs showing pink color on the back skin were used. The epilating hair was carefully removed using a clipper and a razor for electric animals, and the remaining hair was removed using a hair removal agent. 150 μl of the sample was applied daily to each site using a brush. Samples were treated daily at 10 am for 3 weeks.
실험시료로서 2.5중량%의 저분자량 맥문동 단백다당체(실시예 2)와 2.5중량%의 미녹시딜(Minoxidil)을 사용하였으며, 이들 시료를 실험 시작 후 시험군과 양성대조군의 피부(제모부위)에 매일 도포하였고, 정상대조군에는 식염수(Saline)군과 Base 대조군에는 헤어 토닉 Base를 도포하였다. 실험 시작 후 1주일, 2주일, 3주일에 털이 자라는 상태를 육안으로 관찰하기 위하여 호흡마취를 실시한 후 사진촬영을 실시하였다. 털이 자란 상태의 정도, 즉 육모의 양을 육안으로 관찰하였으며, 제모된 등판면적에 대하여 0~20%(-), 20~40%(+), 40~60%(++), 80~100%(+++)로 정한 기준에 따라서 효능을 판단하였다. As a test sample, 2.5% by weight of low-molecular-weight macromolecular protein polysaccharide (Example 2) and 2.5% by weight of minoxidil were used and these samples were applied daily on the skin of the test group and the positive control group And the hair tonic base was applied to the saline group and the base control group in the normal control group. After 1 week, 2 weeks, and 3 weeks after the start of the experiment, breathing and anesthesia were performed to observe the state of hair growth. (-), 20-40% (+), 40-60% (++), and 80-100 (+) of the epilated backlash area were visually observed, The efficacy was determined according to the criteria set by% (+++).
식염수, Base, 2.5중량% 미녹시딜, 2.5중량% 맥문동 저분자량 단백다당체 각 군에 대하여 실험 전, 7일 후, 14일 후, 21일 후 제모한 부위의 발모상태를 육안으로 관찰한 결과 및 이를 그래프로 나타낸 것을 도 7 및 8에 나타내었다.The hair growth was observed before, 7, 14, and 21 days after the experiment on each group of saline, base, 2.5% by weight minoxidil, 2.5% by weight MacMontan low molecular weight protein polysaccharide. Are shown in Figs. 7 and 8. Fig.
도 7 및 8을 보면, 실험 7일이 지난 후에는 털이 거의 자라지 않았고, 2.5% 미녹시딜 처리군과 2.5% 맥문동 저분자량 단백다당체 처리군에서만 3% 내외의 모발성장율(모발성장부분/제모부분, %)을 나타냄을 확인할 수 있다. 실험 14일이 지난 이후부터 털이 자라는 것이 뚜렷하게 관찰되었으며, 식염수 처리군과 base 처리군에서 모발성장율은 29.1 ± 3.1%, 28.0 ± 2.81%로 나타났고, 2.5% 미녹시딜 처리군과 2.5% 맥문동 저분자량 단백다당체 처리군의 경우에는 57.3 ± 3.5%, 56.2 ± 3.3%로 현저하게 증가하는 경향을 나타내었다. 실험 21일이 지난 이후부터는 모발이 많이 성장하였으며, 식염수 처리군과 base 처리군에서 모발성장율은 71.0 ± 4.2%, 70.1 ± 3.8%로 나타났고, 2.5% 미녹시딜 처리군과 2.5% 맥문동 저분자량 단백다당체 처리군의 경우에는 93.6 ± 4.3%, 95.1 ± 3.93%로 모발이 거의 제모전 모습으로 회복되는 경향을 나타내었다.7 and 8, hair was hardly grown after 7 days of experiment, and hair growth rate (hair growth portion / hair removal portion,%) in the 2.5% minoxidil treated group and 2.5% ). ≪ / RTI > The hair growth rate was 29.1 ± 3.1% and 28.0 ± 2.81% in the saline-treated group and the base-treated group, respectively. The 2.5% minoxidil treated group and the 2.5% And 57.3 ± 3.5% and 56.2 ± 3.3%, respectively, in the polysaccharide treated group. The hair growth rate was 71.0 ± 4.2% and 70.1 ± 3.8% in the saline - treated group and the base - treated group after 21 days of the experiment, and 2.5% minoxidil treated group and 2.5% And 93.6 ± 4.3% and 95.1 ± 3.93% in the treated group, respectively.
따라서, 상기 결과로부터, 맥문동 유래의 저분자량 단백다당체를 처리한 마우스의 등이 동일한 농도(2.5%)의 미녹시딜을 처리한 양성대조군과 유사하게, 피부색이 단시간에 검게 변하며 털이 빨리 자라는 것을 확인하였으며, 이로부터 맥문동 유래의 저분자량 단백다당체가 뛰어난 발모효과를 가짐을 알 수 있다.Therefore, from the above results, it was confirmed that skin color rapidly changed to black and hairy hair grows rapidly in a similar manner to a positive control group treated with the same concentration (2.5%) of minoxidil in mice treated with low molecular weight protein polysaccharide derived from ganoderma lucidum, From this, it can be seen that the low-molecular-weight protein polysaccharide derived from McDonald's had excellent hair growth effect.
[제제예 1] 헤어 토닉[Formulation Example 1] Hair tonic
하기 표 10에 기재된 조성에 따라 통상적인 방법으로 헤어 토닉을 제조하였다.Hair tonics were prepared in a conventional manner according to the composition shown in Table 10 below.
[제제예 2] 헤어 로션[Formulation Example 2] Hair lotion
하기 표 11에 기재된 조성에 따라 통상적인 방법으로 헤어 로션을 제조하였다.Hair lotions were prepared in a conventional manner according to the composition shown in Table 11 below.
[제제예 3] 모발 영양화장수[Formulation Example 3] Hair nutritional lotion
하기 표 12에 기재된 조성에 따라 통상적인 방법으로 모발 영양화장수를 제조하였다.The hair nutritional lotion was prepared by a conventional method according to the composition shown in Table 12 below.
[제제예 4] 헤어 샴푸 [Formulation Example 4] Hair shampoo
하기 표 13에 기재된 조성에 따라 통상적인 방법으로 헤어 샴푸를 제조하였다.Hair shampoos were prepared in a conventional manner according to the composition shown in Table 13 below.
[제제예 5] 헤어 린스[Formulation Example 5] Hair rinse
하기 표 14에 기재된 조성에 따라 통상적인 방법으로 헤어 린스를 제조하였다.Hair rinses were prepared according to the compositions shown in Table 14 below by a conventional method.
[제제예 6] 연고[Formulation Example 6] Ointment
하기 표 15에 기재된 조성에 따라 통상적인 방법으로 연고를 제조하였다.Ointment was prepared by a conventional method according to the composition shown in Table 15 below.
[제형예 7] 연질 캅셀제[Formulation Example 7] Soft capsule
맥문동 단백다당체 50mg, L-카르니틴 80~140mg, 대두유 180mg, 팜유 2mg, 식물성 경화유 8mg, 황납 4mg 및 레시틴 6mg을 혼합하고, 통상의 방법에 따라 1캡슐 당 400mg씩 충진하여 연질 캅셀을 제조한다.A soft capsule is prepared by mixing 400 mg of L-carnitine with 80 mg of L-carnitine, 180 mg of soybean oil, 2 mg of palm oil, 8 mg of vegetable hardening oil, 4 mg of yellow radish and 6 mg of lecithin.
[제형예 8] 정제[Formulation Example 8] Tablets
맥문동 단백다당체 50mg, 갈락토올리고당 200mg, 유당 60mg 및 맥아당 140mg을 혼합하고 유동층 건조기를 이용하여 과립한 후 당 에스테르(sugar ester) 6mg을 첨가하고 타정하여 정제를 제조한다.The mixture is mixed with 50 mg of macromolecular protein polysaccharide, 200 mg of galactooligosaccharide, 60 mg of lactose and 140 mg of maltose, granulated using a fluidized bed drier, and then 6 mg of sugar ester is added and tableted to prepare tablets.
[제형예 9] 과립제[Formulation Example 9]
맥문동 단백다당체 50mg, 무수결정 포도당 250mg 및 전분 550mg을 혼합하고, 유동층 과립기를 사용하여 과립으로 성형한 후 포에 충진한다.50 mg of macromolecular protein polysaccharide, 250 mg of anhydrous crystalline glucose, and 550 mg of starch are mixed and formed into granules by using a fluidized bed granulator and filled in a capsule.
[제형예 10] 드링크제[Formulation Example 10] Drinking agent
맥문동 단백다당체 50mg, 포도당 10g, 구연산 0.6g 및 액상 올리고당 25g을 혼합한 후 정제수 300ml를 가하여 병에 충진한다. 이후 130℃에서 4~5초간 살균하여 음료를 제조한다.50 mg of macromolecular protein polysaccharide, 10 g of glucose, 0.6 g of citric acid and 25 g of liquid oligosaccharide are mixed, and 300 ml of purified water is added to the bottle. The beverage is then sterilized at 130 DEG C for 4 to 5 seconds.
Claims (7)
a) 알코올성 용매에 맥문동을 첨가한 다음, 원심분리를 통해 저분자량의 폴리페놀을 제거하는 단계;
b) 상기 a) 단계에서 저분자량의 폴리페놀을 제거하여 얻은 맥문동 잔사로부터 수용성 활성성분을 30~40℃의 온도에서 열수 추출하고, 필터프레스 여과 및 농축하여 농축액을 얻는 단계; 및
c) 상기 b) 단계에서 얻은 농축액으로부터 알코올 침전 반응 후, 필터프레스 적용하여 알코올이 제거된 맥문동 단백다당체를 분리하는 단계
를 포함하는 방법으로 제조된 것임을 특징으로 하는, 피부 외용제 조성물.The method of claim 1, wherein the protein polysaccharide
a) adding ginseng root to the alcoholic solvent, and then removing the low molecular weight polyphenol by centrifugation;
b) hydrolyzing the water-soluble active ingredient from the germanium residue obtained by removing the low molecular weight polyphenol in step a) at a temperature of 30 to 40 ° C, filtering the resultant by filtration, and concentrating to obtain a concentrated liquid; And
c) separating the alcohol-removed macromolecular protein polysaccharide by applying a filter press after the alcohol precipitation reaction from the concentrate obtained in the step b)
Wherein the external preparation is prepared by a method comprising the steps of:
d) 상기 c) 단계에서 얻은 맥문동 단백다당체로부터 한외여과 실시하여 분자량 별로 분리하는 단계를 추가로 포함함을 특징으로 하는, 피부 외용제 조성물.5. The method of claim 4,
d) performing ultrafiltration from the marshmallow gelatinized protein polysaccharide obtained in the step c) to separate the liposomes according to their molecular weights.
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