KR20180053278A - Composition for Improving Atopic Dermatitis Using Fermented Products of Fruit of Diospyros kaki - Google Patents
Composition for Improving Atopic Dermatitis Using Fermented Products of Fruit of Diospyros kaki Download PDFInfo
- Publication number
- KR20180053278A KR20180053278A KR1020180036629A KR20180036629A KR20180053278A KR 20180053278 A KR20180053278 A KR 20180053278A KR 1020180036629 A KR1020180036629 A KR 1020180036629A KR 20180036629 A KR20180036629 A KR 20180036629A KR 20180053278 A KR20180053278 A KR 20180053278A
- Authority
- KR
- South Korea
- Prior art keywords
- atopic dermatitis
- composition
- fermented
- present
- improving atopic
- Prior art date
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Abstract
Description
본 발명은 감(Diospyros kaki) 발효물을 이용한 아토피성 피부염 개선용 조성물에 관한 것으로, 구체적으로는 감을 유용미생물인 젖산균, 광합성세균 및 효모로 발효시켜 얻은 발효물을 이용한 아토피성 피부염 개선용 조성물에 관한 것이다.The invention persimmon (Diospyros The present invention relates to a composition for improving atopic dermatitis using a fermented product obtained by fermenting a sensate with useful microorganisms such as lactic acid bacteria, photosynthetic bacteria and yeast.
아토피는 '괴상한' 또는 "부적절한"의 의미를 가지는 라틴어 'atopia'에서 유래한 말인데, 아토피(atopy)성 피부염은 심한 가려움증, 만성 피부 발진이 특징인 질환으로, 영유아기 습진의 가장 흔한 형태이다.Atopic dermatitis is characterized by severe itching and chronic skin rash. It is the most common form of infantile eczema. It is caused by atopic dermatitis.
아토피성 피부염의 원인은 아직까지 명확히 규명되어 있지 않지만, IgE 생성의 증가, CD8+ 억제/세포독성 T 림프구 (CD8+ suppressor/cytotoxic T lymphocytes) 수적 감소와 기능 저하, 단핵구/대식세포의 침윤, 비만세포, 호산구, 수지상세포(dendritic cells; DCs), 표피의 랑게르한스 세포 및 CD4+ T 림프구의 수적 증가, 케모카인(TSLP, RANTES, CTACK, LARC, MDC, TARC 등)의 생성 증가 등의 면역학적 현상들이 보고되어 있다(J. Invest. Dermatol., 96:523-526, 1991; J. Invest Dermatol., 97:389-394, 1991; Immunol., 11:81-88, 1999; Curr Drug Targets Inflamm Allergy., 2:199-120, 2003; J. Allergy Clin Immunol., 107:871-877, 2001; Adv. Immunol. 78:57, 2001; International Immunology, 14(7):767-773, 2002; Pediatr Allergy Immunol 19: 605-613, 2008).The cause of atopic dermatitis has not yet been elucidated yet. However, the cause of atopic dermatitis has not yet been clarified. However, it has been reported that increased IgE production, decreased CD8 + suppression / cytotoxic T lymphocytes, decreased function and dysfunction, monocyte / macrophage infiltration, There have been reported immunological phenomena such as increased numbers of eosinophils, dendritic cells (DCs), epidermal Langerhans cells and CD4 + T lymphocytes, and increased production of chemokines (TSLP, RANTES, CTACK, LARC, MDC, TARC etc.) (Invest. Dermatol., 96: 523-526,1991, J. Invest Dermatol., 97: 389-394,1991, Immunol., 11: 81-88,1999, Curr Drug Targets Inflamm Allergy., 2: International Immunology, 14 (7): 767-773, 2002; Pediatr Allergy Immunol 19: 711-120, 2003; J. Allergy Clin Immunol., 107: 871-877, 2001; Adv. Immunol. 605-613, 2008).
특히 아토피성 피부염 환자에서 케모카인인 MDC(macrophage-derived chemokine)와 TARC(thymusand activation-regulated chemokine)의 혈청 농도가 현저히 증가한다는 보고가 있고(Hijnen et. al., J. Allergy Clin. Immunol. 113(2) 334-340), 아토피성 피부염의 치료 물질로 사용되는 사이크로스포린 A나 코르티코스테로이드를 아토피성 피부염 환자에게 투여하였을 때는 MDC 및 TARC의 혈청 농도가 감소한다는 보고가 있으며(Y. Shimada et al., J. Dermatol. Sci., 34, 201-208, 2004), 또 시험관내 실험에서 HaCaT 세포에 INF-γ나 TNF-α를 처리하였을 때 MDC 및 TARC가 다량 발현되는데 이러한 발현을 억제할 수 있는 물질은 아토피성 피부염 치료제로 사용될 수 있음이 제시된 바 있다(Horikawa et. al., Int. Immunol., 14(7) 767-773, 2002).In particular, serum concentrations of macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC) have been reported to be significantly increased in patients with atopic dermatitis (Hijnen et al., J. Allergy Clin. Immunol. 2) 334-340), when ciclosporin A or corticosteroids, used as therapeutic agents for atopic dermatitis, were administered to patients with atopic dermatitis, serum concentrations of MDC and TARC were reported to decrease (Y. Shimada et al In vitro studies have shown that MDC and TARC are highly expressed when HaCaT cells are treated with INF-γ or TNF-α, which can inhibit this expression (see, for example, J. Dermatol. Sci., 34, 201-208, 2004) (Horikawa et al., Int. Immunol., 14 (7) 767-773, 2002).
따라서 MDC나 TARC의 발현을 억제하는 물질 등은 아토피성 피부염 개선제로 활용될 수 있다. Therefore, a substance that inhibits the expression of MDC or TARC can be used as a remedy for atopic dermatitis.
본 발명은 INF-γ와 TNF-α로 자극된 HaCaT 세포에서 MDC 및 TARC의 발현을 억제하며, 실제 임상 평가에서도 아토피성 피부염 개선 활성을 가지는 감의 유용미생물에 의한 발효물을 개시한다. The present invention discloses a fermented product of useful microorganisms which inhibit the expression of MDC and TARC in HaCaT cells stimulated with IFN-? And TNF- ?, and has an activity of improving atopic dermatitis in actual clinical evaluation.
본 발명의 목적은 감의 유용미생물 발효물을 이용한 아토피성 피부염 개선용 조성물을 제공하는 데 있다.It is an object of the present invention to provide a composition for improving atopic dermatitis using a fermented microorganism useful as a persimmon.
본 발명의 다른 목적이나 구체적인 목적은 이하에서 제시될 것이다.Other and further objects of the present invention will be described below.
본 발명자들은 감(과실)을 유용미생물인 젖산균, 광합성세균 및 효모로 발효시켜 얻은 발효물의 아토피성 피부염 개선 활성을 hIFN-γ, TNF-α로 처리된 HaCaT 세포에 처리하여 MDC 및 TARC 생성 억제 활성을 통하여 확인한 결과, 감의 70% 에탄올 추출물과 유용미생물 자체 발효물에 비해 뚜렷하게 높은 활성을 보임을 확인하였으며, 이러한 세포실험 결과에 기초하여 감 70% 에탄올 추출물, 감의 유용미생물 발효물 그리고 유용미생물 자체의 발효물이 각각 함유된 3종의 영양로션을 이용하여 8주간의 임상시험을 실시하였을 때도, 세포실험에서 활성이 높은 것으로 확인된 감의 유용미생물 발효물이 감 70% 에탄올 추출물이나 유용미생물 자체의 발효물에 비해서 뚜렷하게 높은 아토피성 피부염 개선 활성을 보임을 확인하였다.The present inventors treated HaCaT cells treated with hIFN-γ and TNF-α to inhibit the production of MDC and TARC by treating atrophic dermatitis improving activity of a fermented product obtained by fermenting persimmon (fruit) with useful microorganisms such as lactic acid bacteria, photosynthetic bacteria and yeast The results showed that the 70% ethanol extract and the fermented microorganism of the useful microorganism showed higher activity than the 70% ethanol extract of the fermented microorganism. When the fermented microorganism fermented in a cell test was found to have a high activity even after 8 weeks of clinical trials using three nutritional lotions each containing its own fermented product, And showed markedly higher activity of atopic dermatitis improving activity than the fermented product itself.
본 발명은 이러한 실험 결과에 기초하여 제공되는 것으로, 본 발명의 아토피성 피부염 개선용 조성물은 감 과실의 젖산균, 광합성세균 및 효모 발효물을 유효성분으로 포함함을 특징으로 한다.The present invention is provided based on these experimental results, and the composition for improving atopic dermatitis of the present invention is characterized by containing lactic acid bacteria, photosynthetic bacteria and yeast fermented products as an effective ingredient.
본 명세서에서, 상기 "유효성분"의 의미는 단독으로 목적하는 활성을 나타내거나 또는 그 자체는 활성이 없는 담체와 함께 활성을 나타낼 수 있는 성분을 의미한다.Herein, the meaning of the above-mentioned "active ingredient" means an ingredient that alone exhibits the desired activity or can exhibit activity together with a carrier which is itself inactive.
또 본 명세서에서, "아토피성 피부염"은 그 발생의 직·간접적인 원인을 불문하고 당업계에서 아토피성 피부염으로 분류되는 모든 질환을 포함하는 것으로 정의된다. 통상 아토피성 피부염은 그 발병 시기 또는 그 발명 대상에 따라 유아형 아토피성 피부염, 소아형 아토피성 피부염, 성인형 아토피성 피부염 그리고 임산부 아토피성 피부염으로 분류되는데, 본 명세서에서 아토피성 피부염은 이러한 모든 유형의 아토피성 피부염을 포함한다.As used herein, "atopic dermatitis" is defined as including any disease classified as atopic dermatitis in the art, regardless of the cause, either directly or indirectly, of its occurrence. In general, atopic dermatitis is classified into infantile atopic dermatitis, pediatric atopic dermatitis, adult atopic dermatitis, and maternal atopic dermatitis according to the onset period or the object of the invention. In the present specification, Of atopic dermatitis.
또 본 명세서에서 "발효물"은 그 발효 대상인 감 과실에 탄소원을 첨가하고 젖산균, 광합성세균 및 효모 접종·배양하여 얻어진 배양물을 의미한다. 이 배양물은 그대로 이용되거나, 감압농축 및/또는 동결건조시켜 액상 또는 분말상으로 이용되거나, 메탄올, 에탄올 등의 탄소수 1 내지 4의 알콜, 아세톤, 에틸아세테이트, 클로로포름, 메틸렌클로라이드, 물, 또는 이들의 혼합 용매로 추출하여 이용될 수 있다. 또한 메탄올, 에탄올 등의 탄소수 1 내지 4의 알콜, 아세톤, 에틸아세테이트, 클로로포름, 메틸렌클로라이드, 물, 또는 이들의 혼합 용매로 추출하여 이용할 수도 있다. 이러한 추출물은 추출 용매가 일부 또는 전부 제거된 액상 또는 분말상일 수 있다. In the present specification, the term "fermented product" means a culture obtained by adding a carbon source to a sensory fruit to be fermented and obtained by inoculating and culturing lactic acid bacteria, photosynthetic bacteria and yeast. The culture may be used as it is, or may be used in liquid or powder form by concentration under reduced pressure and / or lyophilization, or may be used in the form of a liquid or a powder, or an alcohol having 1 to 4 carbon atoms such as methanol and ethanol, acetone, ethyl acetate, chloroform, methylene chloride, It can be used by extracting with a mixed solvent. It may also be extracted with an alcohol having 1 to 4 carbon atoms such as methanol and ethanol, acetone, ethyl acetate, chloroform, methylene chloride, water or a mixed solvent thereof. Such an extract may be in liquid or powder form in which part or all of the extraction solvent has been removed.
상기에서 접종되는 미생물의 탄소원은 당업계에 잘 알려져 있고, 따라서 당업계에 알려진 임의의 것을 사용할 수 있는데, 통상은 올리고당, 유당, 포도당, 과당, 설탕, 당밀, 덱스트로스, 이들의 혼합물 등이 사용될 것이다. 이러한 탄소원은 의도한 발효 시간, 발효 정도 등을 고려하여 임의의 범위로 첨가될 수 있다. 통상 발효 대상인 감 100 중량부 기준 1 중량부 내지 70 중량부의 범위로 첨가될 것이다. The carbon source of the microorganism inoculated in the above is well known in the art, and thus any of those known in the art can be used. Usually, oligosaccharides, lactose, glucose, fructose, sugar, molasses, dextrose, will be. These carbon sources can be added in an arbitrary range in consideration of the intended fermentation time, degree of fermentation, and the like. It is usually added in the range of 1 to 70 parts by weight based on 100 parts by weight of the fermentation target.
또 상기에서 미생물의 접종 후의 배양은 5℃~45℃의 온도 조건 특히 25℃~40℃의 온도 조건에서 이루어질 수 있다. 배양 온도가 상기 범위보다 낮을 경우 발효 속도가 느려질 수 있고 또한 원하지 않는 발효 산물이 생겨날 수 있으며, 배양 온도가 상기 범위보다 높을 경우도 발효 미생물의 사멸에 따라 마찬가지로 발효 속도가 느려지거나 원하지 발효 산물이 생겨날 수 있다. 배양 시간의 경우는 접종된 미생물의 생장이 최대에 이를 때까지 지속되는 것이 바람직하다. 접종된 미생물이 생장이 최대에 이르는 시점은 배양 온도, 발효 원료의 양, 접종되는 미생물의 양 등에 따라 결정될 것이다. In addition, the cultivation after inoculation of the microorganisms can be carried out at a temperature condition of 5 ° C to 45 ° C, particularly at a temperature of 25 ° C to 40 ° C. If the incubation temperature is lower than the above range, the fermentation rate may be slowed and unwanted fermentation products may be produced. Even if the incubation temperature is higher than the above range, the fermentation rate may be similarly slowed down due to the death of the fermentation microorganisms, . In the case of the incubation time, it is preferable to continue until the growth of the inoculated microorganism reaches a maximum. The time at which the inoculated microorganism reaches its maximum growth will depend on the incubation temperature, the amount of fermentation material, the amount of microorganisms inoculated, and so on.
본 발명의 아토피성 피부염 개선용 조성물은 그 유효성분인 감 발효물을 아토피성 피부염 개선 활성을 나타낼 수 있는 한 용도, 제형, 배합 목적 등에 따라 임의의 양(유효량)으로 포함할 수 있는데, 통상적인 유효량은 조성물 전체 중량을 기준으로 할 때 0.001 중량 % 내지 99.900 중량 % 범위 내에서 결정될 것이다. 여기서 "유효량"이란 아토피성 피부염의 예방, 개선, 치료, 또는 그 증상의 발현 지연을 유도할 수 있는 유효성분의 양을 말한다. 이러한 유효량은 당업자의 통상의 능력 범위 내에서 실험적으로 결정될 수 있다.The composition for improving atopic dermatitis of the present invention may contain any amount (effective amount) of the active ingredient decaf fermented product, depending on the purpose of use, formulation, compounding purpose, and the like, which can exhibit atopic dermatitis improving activity. An effective amount will be determined within the range of from 0.001 wt% to 99.900 wt% based on the total weight of the composition. The term "effective amount" as used herein refers to an amount of an effective ingredient capable of preventing, ameliorating, treating, or delaying the onset of symptoms of atopic dermatitis. Such effective amounts can be determined experimentally within the ordinary skill of those skilled in the art.
본 발명의 아토피성 피부염 개선용 조성물은 구체적인 양태에 있어서, 식품 조성물로 파악할 수 있다.The composition for improving atopic dermatitis of the present invention can be identified as a food composition in a specific embodiment.
본 발명의 조성물이 식품 조성물로 파악될 경우, 식품의 형태는 차, 쥬스, 탄산음료, 이온음료 등의 음료류, 우유, 요구루트 등의 가공 유류, 껌류, 떡, 한과, 빵, 과자, 면 등의 식품류, 산제, 정제, 캡슐제 등의 건강식품 제제류 등이 될 수 있다.When the composition of the present invention is identified as a food composition, the form of the food is not particularly limited as far as it is a beverage such as tea, juice, carbonated beverage, ionic drink, processed oil such as milk and request route, gum, rice cake, Food preparations such as foods, powders, tablets, capsules and the like.
본 발명의 식품 조성물에는 그 유효성분 이외에 감미제, 풍미제, 생리활성 성분, 미네랄 등이 포함될 수 있다.The food composition of the present invention may contain sweetening agents, flavoring agents, physiologically active ingredients, minerals and the like in addition to the active ingredients thereof.
감미제는 식품이 적당한 단맛을 나게 하는 양으로 사용될 수 있으며, 천연의 것이거나 합성된 것일 수 있다. 바람직하게는 천연 감미제를 사용하는 경우인데, 천연 감미제로서는 옥수수 시럽 고형물, 꿀, 수크로오스, 프룩토오스, 락토오스, 말토오스 등의 당 감미제를 들 수 있다. Sweetening agents may be used in an amount that sweetens the food in a suitable manner, and may be natural or synthetic. Preferably, natural sweeteners are used. Examples of natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose and maltose.
풍미제는 맛이나 향을 좋게 하기 위하여 사용될 수 있는데, 천연의 것과 합성된 것 모두 사용될 수 있다. 바람직하게는 천연의 것을 사용하는 경우이다. 천연의 것을 사용할 경우에 풍미 이외에 영양 강화의 목적도 병행할 수 있다. 천연 풍미제로서는 사과, 레몬, 감귤, 포도, 딸기, 복숭아 등에서 얻어진 것이거나 녹차잎, 둥굴레, 대잎, 계피, 국화 잎, 자스민 등에서 얻어진 것일 수 있다. 또 인삼(홍삼), 죽순, 알로에 베라, 은행 등에서 얻어진 것을 사용할 수 있다. 천연 풍미제는 액상의 농축액이나 고형상의 추출물일 수 있다. 경우에 따라서 합성 풍미제가 사용될 수 있는데, 합성 풍미제는 에스테르, 알콜, 알데하이드, 테르펜 등이 이용될 수 있다. Flavors may be used to enhance taste or flavor, both natural and synthetic. Preferably, a natural one is used. When using natural ones, the purpose of nutritional fortification can be performed in addition to the flavor. Examples of natural flavoring agents include those obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or those obtained from green tea leaves, Asiatica, Daegu, Cinnamon, Chrysanthemum leaves and Jasmine. Also, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, banks and the like can be used. The natural flavoring agent may be a liquid concentrate or a solid form of extract. Synthetic flavors may be used depending on the case, and synthetic flavors such as esters, alcohols, aldehydes, terpenes and the like may be used.
생리 활성 물질로서는 카테킨, 에피카테킨, 갈로가테킨, 에피갈로카테킨 등의 카테킨류나, 레티놀, 아스코르브산, 토코페롤, 칼시페롤, 티아민, 리보플라빈 등의 비타민류 등이 사용될 수 있다.Examples of the physiologically active substance include catechins such as catechin, epicatechin, gallocatechin and epigallocatechin, and vitamins such as retinol, ascorbic acid, tocopherol, calciferol, thiamine and riboflavin.
미네랄로서는 칼슘, 마그네슘, 크롬, 코발트, 구리, 불소화물, 게르마늄, 요오드, 철, 리튬, 마그네슘, 망간, 몰리브덴, 인, 칼륨, 셀레늄, 규소, 나트륨, 황, 바나듐, 아연 등이 사용될 수 있다.As the mineral, calcium, magnesium, chromium, cobalt, copper, fluoride, germanium, iodine, iron, lithium, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, silicon, sodium, sulfur, vanadium and zinc can be used.
또한 본 발명의 식품 조성물은 상기 감미제 등 이외에도 필요에 따라 보존제, 유화제, 산미료, 점증제 등을 포함할 수 있다. In addition, the food composition of the present invention may contain preservatives, emulsifiers, acidifiers, thickeners and the like as needed in addition to the above sweeteners.
이러한 보존제, 유화제 등은 그것이 첨가되는 용도를 달성할 수 있는 한 극미량으로 첨가되어 사용되는 것이 바람직하다. 극미량이란 수치적으로 표현할 때 식품 조성물 전체 중량을 기준으로 할 때 0.0005중량% 내지 약 0.5중량% 범위를 의미한다.Such preservatives, emulsifiers and the like are preferably added in a very small amount as long as they can attain an application to which they are added. The term " trace amount " means, when expressed numerically, in the range of 0.0005% by weight to about 0.5% by weight based on the total weight of the food composition.
사용될 수 있는 보존제로서는 소듐 소르브산칼슘, 소르브산나트륨, 소르브산칼륨, 벤조산칼슘, 벤조산나트륨, 벤조산칼륨, EDTA(에틸렌디아민테트라아세트산) 등을 들 수 있다. Examples of the preservative which can be used include calcium sodium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate and EDTA (ethylenediaminetetraacetic acid).
사용될 수 있는 유화제로서는 아카시아검, 카르복시메틸셀룰로스, 잔탄검, 펙틴 등을 들 수 있다.Examples of the emulsifier which can be used include acacia gum, carboxymethyl cellulose, xanthan gum, pectin and the like.
사용될 수 있는 산미료로서는 연산, 말산, 푸마르산, 아디프산, 인산, 글루콘산, 타르타르산, 아스코르브산, 아세트산, 인산 등을 들 수 있다. 이러한 산미료는 맛을 증진시키는 목적 이외에 미생물의 증식을 억제할 목적으로 식품 조성물이 적정 산도로 되도록 첨가될 수 있다.Examples of the acidulant that can be used include acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, and phosphoric acid. Such an acidulant may be added so that the food composition has a proper acidity for the purpose of inhibiting the growth of microorganisms other than the purpose of enhancing the taste.
사용될 수 있는 점증제로서는 현탁화 구현제, 침강제, 겔형성제, 팽화제 등을 들 수 있다. Agents that may be used include suspending agents, sedimentation agents, gel formers, bulking agents and the like.
본 발명의 아토피성 피부염 개선용 조성물은 다른 구체적인 양태에 있어서 약제학적 조성물로 파악될 수 있다.The composition for improving atopic dermatitis of the present invention can be identified as a pharmaceutical composition in another specific embodiment.
본 발명의 약제학적 조성물은 그 유효성분 이외에 약제학적으로 허용되는 담체, 부형제 등을 포함하여, 국소형 제형 예컨대 크림, 로션, 연고(반고형의 외용약), 마이크로로에멀젼, 젤, 페이스트, 경피제제(TTS)(예컨대 패치제, 붕대 등) 등으로 제조될 수 있다.The pharmaceutical composition of the present invention may be formulated into a wide variety of dosage forms, including pharmaceutically acceptable carriers, excipients and the like, in addition to the active ingredient, and may be formulated into a wide variety of dosage forms such as a localized preparation such as cream, lotion, ointment (semi-solid external drug), micro loo emulsion, (TTS) (e.g., patches, bandages, etc.), and the like.
상기에서 "약제학적으로 허용되는" 의미는 유효성분의 활성을 억제하지 않으면서 적용(처방) 대상이 적응가능한 이상의 독성을 지니지 않는다는 의미이다.The term "pharmaceutically acceptable" as used herein means that the application (prescribing) subject does not have the above-mentioned toxicity that is adaptable without inhibiting the activity of the active ingredient.
약제학적으로 허용되는 담체의 예로서는 락토스, 글루코스, 슈크로스, 전분(예컨대 옥수수 전분, 감자 전분 등), 셀룰로오스, 그것의 유도체(예컨대 나트륨 카르복시메틸 셀룰로오스, 에틸셀룰로오스, 등), 맥아, 젤라틴, 탈크, 고체 윤활제(예컨대 스테아르산, 스테아르산 마그네슘 등), 황산 칼슘, 식물성 기름(예컨대 땅콩 기름, 면실유, 참기름, 올리브유 등), 폴리올(예컨대 프로필렌 글리콜, 글리세린 등), 알긴산 등을 들 수 있으며 이러한 담체는 본 발명의 약제학적 조성물의 제형에 따라 적당한 것을 하나 이상 선택하여 사용할 수 있다. 약제학적으로 허용되는 적합한 담체와 제제에 대해서는 문헌[Remington's Pharmaceutical Sciences(19th ed., 1995)]을 참조할 수 있다. 본 발명의 약제학적 조성물은 유화제(예컨대 TWEENS), 습윤제(예컨대 라우릴 황산 나트륨), 착색제, 풍미제, 안정화제, 보존제, 물, 식염수, 인산염 완충 용액 등을 추가로 포함할 수 있다. Examples of pharmaceutically acceptable carriers include lactose, glucose, sucrose, starch (e.g. corn starch, potato starch, etc.), cellulose, derivatives thereof (e.g. sodium carboxymethylcellulose, ethylcellulose, etc.), malt, gelatin, talc, (E.g., peanut oil, cottonseed oil, sesame oil, olive oil, etc.), polyols (e.g., propylene glycol, glycerin and the like), alginic acid, and the like. Depending on the formulation of the pharmaceutical composition of the present invention, one or more suitable ones may be selected and used. Suitable pharmaceutically acceptable carriers and formulations are described in Remington's Pharmaceutical Sciences (19th ed., 1995). The pharmaceutical composition of the present invention may further comprise an emulsifier (e.g., TWEENS), a wetting agent (e.g., sodium lauryl sulfate), a coloring agent, a flavoring agent, a stabilizer, a preservative, water, saline, a phosphate buffer solution and the like.
부형제도 본 발명의 약제학적 조성물의 제형에 따라 적합한 것을 선택하여 사용할 수 있는데, 예컨대 나트륨 카르복시메틸 셀룰로오스, 메틸 셀룰로오스, 히드로프로필메틸셀룰로오스, 알긴산 나트륨, 폴리비닐피롤리돈 등의 현탁제나 분산제 등을 들 수 있다. The excipient may be selected according to the formulation of the pharmaceutical composition of the present invention. For example, suspending agents such as sodium carboxymethyl cellulose, methyl cellulose, hydropropyl methyl cellulose, sodium alginate, polyvinyl pyrrolidone, .
본 발명의 약제학적 조성물은 그 1일 투여량이 통상 0.001 ~ 150 mg/kg 체중 범위이고, 1회 또는 수회로 나누어 투여할 수 있다. 그러나, 본 발명의 약제학적 조성물의 투여량은 투여 경로, 환자의 연령, 성별, 체중, 환자의 중증도 등의 여러 관련 인자에 비추어 결정되는 것이므로 상기 투여량은 어떠한 측면으로든 본 발명의 범위를 제한하는 것으로 이해되어서는 아니 된다.The daily dose of the pharmaceutical composition of the present invention is usually 0.001 to 150 mg / kg body weight, and may be administered once or several times. However, since the dosage of the pharmaceutical composition of the present invention is determined in view of various related factors such as route of administration, age, sex, weight, and patient's severity of the patient, the dose is limited in any aspect to the scope of the present invention Should not be understood to be.
본 발명의 아토피성 피부염 개선용 조성물은 또 다른 구체적인 양태에 있어서, 화장료 조성물로 파악할 수 있다.The composition for improving atopic dermatitis of the present invention can be identified as a cosmetic composition in another specific embodiment.
본 발명의 화장료 조성물은 아토피성 피부염 개선 활성을 나타내는 유효성분인 감 발효물 이외에 화장료 조성물에 통상적으로 이용되는 성분들, 예컨대, 안정화제, 용해화제, 계면활성제, 비타민, 색소 및 항료와 같은 통상적인 보조제, 및 담체를 포함할 수 있다. The cosmetic composition of the present invention may contain, in addition to the active ingredient which exhibits the atopic dermatitis-improving activity, an active ingredient such as a conventionally used ingredient in the cosmetic composition such as a stabilizer, a solubilizing agent, a surfactant, a vitamin, Adjuvants, and carriers.
본 발명의 화장료 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어, 용액, 현탁액, 유탁액, 페이스트, 겔, 크림, 로션, 파우더, 비누, 계면활성제-함유 클린싱, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션 및 스프레이 등으로 제형화될 수 있으나, 이에 한정되는 것은 아니다. 보다 상세하게는, 유연 화장수, 영양 화장수, 영양 크림, 마사지 크림, 에센스, 아이 크림, 클렌징 크림, 클렌징 포옴, 클렌징 워터, 팩, 스프레이 또는 파우더의 제형으로 제조될 수 있다.The cosmetic composition of the present invention can be prepared into any of the formulations conventionally produced in the art and can be used as a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, , Oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, it can be manufactured in the form of a soft lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder.
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, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .
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. In the case of a spray, in particular, / Propane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 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.In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.
본 발명의 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters.
본 발명의 화장료 조성물은 아토피성 피부염 개선 활성을 나타내는 감 발효물을 포함하는 것을 제외하고는 당업계에 통상적으로 행하여지는 화장료 조성물의 제조방법에 따라 제조할 수 있다.The cosmetic composition of the present invention can be produced according to a method for producing a cosmetic composition which is usually carried out in the art, except that it contains a sensitive fermentation product exhibiting atopic dermatitis improving activity.
전술한 바와 같이, 본 발명에 따르면 감 발효물을 이용한 아토피성 피부염 개선용 조성물을 제공할 수 있다. As described above, the present invention can provide a composition for improving atopic dermatitis using a reduced fermented product.
본 발명의 조성물은 화장품, 약품, 식품 등으로 제품화되어 이용될 수 있다.The composition of the present invention can be used as a cosmetic product, medicine, food or the like.
도 1 및 2는 감 발효물의 TARC와 MDC 생성 억제 활성을 보여주는 결과이다.
도 3은 감 발효물의 세포독성 실험 결과이다.Figures 1 and 2 show the results of showing inhibitory activities of TARC and MDC on the reduced fermented product.
Fig. 3 shows the cytotoxicity test result of the reduced fermented product.
이하 본 발명을 실시예 및 실험예를 참조하여 설명한다. 그러나 본 발명의 범위가 이러한 실시예 및 실험예에 한정되는 것은 아니다.Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these examples and experimental examples.
<< 실시예Example > > 재래감의Traditional 유용미생물에 의한 By useful microorganisms 발효물의Fermented 제조 Produce
제주에서 재배되는 재래감(Diospyros kaki, 과실)을 구입하여 수세하고 분쇄하여 얻은 분쇄물 100 중량부, 그 분쇄물 100 중량부 기준 당밀 50 중량부 및 그 분쇄물 100 중량부 기준 물 300 중량부를 혼합하고, 이 혼합물에 LB 배지에서 준비한 광합성세균 로도슈도모나스 팔루스트리스(Rhodopseudomonas palustris) 배양액 2%(v/v), MRS 액체 배지에서 준비한 젖산균 락토바실러스 플란타럼(Lactobacillus plantarum) 배양액 2%(v/v) 및 PDB 배지에서 준비한 효모 사카로마이세스 세레비시애(Saccaromyces cerevisiae) 배양액 2%(v/v)를 접종하고 30~40℃의 온도 범위에서 배양하여 감 발효물을 얻었다. 발효물은 자외선을 조사하여 살균한 후 감압농축하고 동결건조하여 실험에 사용하였다. 100 parts by weight of crushed product obtained by purchasing, washed and washed by purchasing Diospyros kaki (fruit) cultivated in Jeju, 50 parts by weight of molasses on the basis of 100 parts by weight of the crushed product, and 300 parts by weight of crushed product , And the photosynthetic bacterium prepared in the LB medium for this mixture was also used as
<< 비교예Comparative Example > > 감 추출물 및 유용미생물 자체 Sensory extracts and useful microorganisms themselves 발효물의Fermented 제조 Produce
<비교예 1> 감 추출물의 제조 ≪ Comparative Example 1 > Preparation of persimmon extract
제주에서 재배되는 감(과실)을 구입하여 수세하고 분쇄하여 얻은 분쇄물 100 중량부에 5배 중량의 70% 에탄올을 가하고 24시간 동안 상온에서 추출한 후 여과하고 그 여과액을 감압농축하고 동결건조하여 감 추출물을 제조하였다. Five percent by weight of 70% ethanol was added to 100 parts by weight of the pulverized product obtained by purchasing a persimmon grown in Jeju, washed and ground, and the mixture was extracted at room temperature for 24 hours, filtered, concentrated under reduced pressure and lyophilized Sensitive extract.
<비교예 2> 유용미생물 자체 발효물 제조 ≪ Comparative Example 2 > Preparation of self- fermented microorganism
상기 실시예와 동일하게 유용미생물 발효물을 제조하되, 감 분쇄물을 제외하고 당밀 100 중량부 및 물 600 중량부를 혼합하고 여기에 광합성세균, 젖산균 및 효모를 접종 배양하여 유용미생물 자체의 발효물을 제조하였다. 그 발효물은 자외선을 조사하여 살균한 후 감압농축하고 동결건조하여 실험에 사용하였다. A fermented product of useful microorganisms was prepared in the same manner as in the above example except that 100 parts by weight of molasses and 600 parts by weight of water were mixed except for the pulverized product, and the photosynthetic bacteria, lactic acid bacteria and yeast were inoculated therein, . The fermented product was sterilized by irradiating ultraviolet rays, concentrated under reduced pressure, and lyophilized to be used in the experiment.
<< 실험예Experimental Example > > 항아토피Anti-atopic 활성 실험 Active experiment
<실험예 1> 아토피성 피부염 유발 인자인 TARC 와 MDC 생성 억제 활성 평가 <Experimental Example 1> Evaluation of inhibitory activity of TARC and MDC , a causative agent of atopic dermatitis
HaCaT 세포(3.0×105cells/mL)를 DMEM 배지를 이용하여 세포수를 조절한 후 24 well plate 에 접종하고, 5% CO2 항온기에서 18시간 전 배양 하였다. 이후 배지를 제거하고 HaCaT 세포는 시료 50 ㎕와 450 ㎕의 TNF-α(10 ng/mL)+IFN-γ(10 ng/mL)를 함유한 새로운 배지를 동시에 처리하였고 전배양과 동일 조건에서 배양하였다. 24 시간 후 배양 배지를 원심분리 (12,000 rpm, 3 분)하여 얻어진 상층액의 아토피 유발 인자 생성 함량을 측정하였다. TARC와 MDC의 정량은 mouse enzyme-linked immnunosorbent assay (ELISA) kit (R&D Systems Inc., Minneapolis, MN, USA)를 이용하여 정량하였으며 standard에 대한 표준곡선의 r2값은 0.99 이상이었다.HaCaT cells (3.0 × 10 5 cells / mL) were inoculated into a 24-well plate and DMEM culture medium. Cells were cultured in a 5% CO 2 incubator for 18 hours. After the medium was removed, HaCaT cells were treated with 50 μl of sample and 450 μl of TNF-α (10 ng / ml) + IFN-γ (10 ng / ml) Respectively. After 24 hours, the culture medium was centrifuged (12,000 rpm, 3 minutes), and the amount of atopy inducing factor produced in the supernatant was measured. Determination of TARC and MDC was quantified using the mouse enzyme-linked immnunosorbent assay (ELISA ) kit (R & D Systems Inc., Minneapolis, MN, USA)
결과를 [도 1] 및 [도 2]에 나타내었다. [도 1] 및 [도 2]를 참조하여 보면, 감 추출물(Sample 1, 100, 200 및 400 ㎍/㎖ 처리)이나 유용미생물 자체 발효물(Sample 3, 100, 200 및 400 ㎍/㎖ 처리)는 특별한 MDC 및 TARC 생성 억제 활성을 보이지 않았으나 감의 유용미생물 발효물(Sample 2, 100, 200 및 400 ㎍/㎖ 처리)은 뚜렷하게 MDC 및 TARC 생성 억제 활성을 보였다.The results are shown in Fig. 1 and Fig. 2. (
<실험예 2> 세포독성 평가 ( LDH assay ) EXPERIMENTAL EXAMPLE 2 Evaluation of cytotoxicity ( LDH assay )
RAW 264.7 세포 (1.5×105 cells/㎖)를 DMEM 배지에 실시예의 시료와 LPS (1 ㎍/㎖)를 동시 처리하여 24시간 배양 한 후 배양 배지를 얻어 3,000 rpm에서 5분간 원심분리 하였다. LDH (lactate dehydrogenase) assay는 non-radioactive cytotoxicity assay kit (Promega)를 이용하여 측정했으며, 96 well plate에 원심 분리하여 얻은 배양 배지 50 ㎕와 reconstituted substrate mix를 50 ㎕를 넣고, 실온에서 30분 반응시킨 후 50 ㎕의 stop solution을 넣은 후 microplate reader (Bio-TEK Instruments Inc., Vermont, WI, USA)를 사용하여 490 nm에서 흡광도를 측정하였다. 각 시료군에 대한 평균 흡광도 값을 구하였으며, 대조군 (LDH control, 1:5000)의 흡광도 값과 비교하여 세포독성을 평가하였다.RAW 264.7 cells (1.5 × 10 5 cells / ml) were co-treated with DMEM medium and LPS (1 μg / ml) in DMEM medium for 24 hours, and then cultured for 3 minutes at 3,000 rpm for 5 minutes. The LDH (lactate dehydrogenase) assay was performed using a non-radioactive cytotoxicity assay kit (Promega). 50 μl of the culture medium obtained by centrifugation on a 96-well plate and 50 μl of the reconstituted substrate mix were added and reacted at room temperature for 30 minutes After adding 50 μl of stop solution, absorbance was measured at 490 nm using a microplate reader (Bio-TEK Instruments Inc., Vermont, WI, USA). The average absorbance values for each sample group were determined and compared with the absorbance values of the control (LDH control, 1: 5000) to evaluate cytotoxicity.
결과를 [도 3]에 나타내었다. [도 3]을 참조하여 보면 감의 유용미생물 발효물이 400 ㎍/㎖ 농도에서 약간의 세포독성을 나타내었을 뿐 모든 시료가 특별한 세포독성을 보이지 않았다. 이는 상기 감의 유용미생물 발효물의 MDC 및 TARC 생성 억제 활성이 세포독성에 의한 결과가 아님을 뒷받침한다.The results are shown in Fig. As shown in FIG. 3, the fermented microorganism fermented product showed slight cytotoxicity at a concentration of 400 μg / ml, but all of the samples showed no specific cytotoxicity. This confirms that the MDC and TARC production inhibitory activity of the useful fermented microorganism is not the result of cytotoxicity.
<실험예 3> 아토피성 피부염 개선 활성에 대한 임상시험 <Experimental Example 3> Clinical trial for improving atopic dermatitis
아토피성 피부염 개선에 대한 임상실험을 위하여 아래의 [표 1]의 성분 및 함량으로 영양 로션을 제조하였다.Nutritional lotions were prepared with the ingredients and contents shown in the following Table 1 for the clinical test for the improvement of atopic dermatitis.
(중량%)content
(weight%)
아토피성 피부염 개선 활성은 5세 이상 아토피성 피부염 증상을 갖고 있는 남녀 60명을 대상으로 3 그룹으로 나눈 다음, 각 그룹에 상기 실시예 또는 비교예의 추출물이 함유된 각 영양로션을 하루 2~3회 8주간 도포하게 하였다.The activity of improving atopic dermatitis was divided into three groups of 60 men and women having symptoms of atopic dermatitis over 5 years old and each nutrient lotion containing the extract of the above example or comparative example was administered twice or three times a day For 8 weeks.
시험 시작 전 및 8주가 지난 후에 SCORAD 지수(The European Task Force on Atopic Dermatitis가 개발한 아토피 중증도 평가 지수로 아토피 증상이 심할수록 높은 수치로 나타남)을 측정하였다.Before and after the start of the study, the SCORAD Index was developed by the European Task Force on Atopic Dermatitis, and the severity of atopic symptoms was high.
결과를 평균 ± 표준편차로로 아래의 [표 2]에 나타내었다.The results are shown in Table 2 below as mean ± standard deviation.
임상시험에 있어서도 감의 유용미생물 발효물 함유 영양로션의 경우 SCORAD 지수를 뚜렷하게 감소시켰으나 다른 영양로션의 경우는 특별한 효과를 나타내지 못하였다.In clinical trials, the SCORAD index was significantly reduced in the nutrient lotion containing fermented microorganism fermented products, but the other nutrient lotions showed no significant effect.
Claims (4)
상기 감 과실 발효물은 감 과실을 로도슈도모나스 팔루스트리스(Rhodopseudomonas palustris), 락토바실러스 플란타럼(Lactobacillus plantarum) 및 사카로마이세스 세레비시애(Saccaromyces cerevisiae)로 혼합 발효시켜 얻어진 것을 특징으로 하는 아토피성 피부염 개선용 조성물.
A fermented product comprising persimmon fruit as an active ingredient,
The persimmon fermented product can be obtained by fermenting persimmon fruit with Rhodopseudomonas The present invention relates to a composition for improving atopic dermatitis, which is obtained by mixing and fermenting Lactobacillus plantarum , Saccharomyces cerevisiae , Lactobacillus plantarum and Saccaromyces cerevisiae .
상기 조성물은 식품 조성물인 것을 특징으로 아토피성 피부염 개선용 조성물.
The method according to claim 1,
The composition for improving atopic dermatitis is a food composition.
상기 조성물은 약제학적 조성물인 것을 특징으로 아토피성 피부염 개선용 조성물.
The method according to claim 1,
The composition for improving atopic dermatitis is a pharmaceutical composition.
상기 조성물은 약제학적 조성물인 것을 특징으로 아토피성 피부염 개선용 조성물.
The method according to claim 1,
The composition for improving atopic dermatitis is a pharmaceutical composition.
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