KR102680125B1 - Composition for enhancing pulmonary function having extract of Rehmannia glutinosa Liboschitz var - Google Patents
Composition for enhancing pulmonary function having extract of Rehmannia glutinosa Liboschitz var Download PDFInfo
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- KR102680125B1 KR102680125B1 KR1020210078558A KR20210078558A KR102680125B1 KR 102680125 B1 KR102680125 B1 KR 102680125B1 KR 1020210078558 A KR1020210078558 A KR 1020210078558A KR 20210078558 A KR20210078558 A KR 20210078558A KR 102680125 B1 KR102680125 B1 KR 102680125B1
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Classifications
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A61K36/18—Magnoliophyta (angiosperms)
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- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/314—Foods, ingredients or supplements having a functional effect on health having an effect on lung or respiratory system
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Abstract
천연 복합 추출물을 함유한 조성물로서 체외 및 동물실험을 통해 미세먼지로 유발된 폐 손상을 개선할 수 있는 효과가 검증된 조성물이 개시된다. 본 발명은 지황, 상엽 및 맥문동의 복합 추출물을 유효성분으로 포함하는 미세먼지로 유발된 폐 손상을 개선하는 조성물을 제공한다.Disclosed is a composition containing natural complex extracts that has been proven effective in improving lung damage caused by fine dust through in vitro and animal experiments. The present invention provides a composition for improving lung damage caused by fine dust, comprising a complex extract of Rehmannia glutinosa, Morifolia lily, and L. vulgaris as active ingredients.
Description
본 발명은 미세먼지 대응 기능성 천연 복합물에 관한 것으로, 보다 상세하게는 미세먼지로 인한 폐 손상을 개선하는 조성물에 관한 것이다.The present invention relates to a functional natural complex against fine dust, and more specifically, to a composition that improves lung damage caused by fine dust.
산업화로 인한 대기오염 및 환경의 변화로 미세먼지로 인한 호흡기 질환이 증가하고 있는 상황이며, 이의 예방 또는 치료에 대한 수요는 증가하고 있다.Respiratory diseases caused by fine dust are increasing due to air pollution and environmental changes due to industrialization, and the demand for prevention or treatment is increasing.
미세먼지는 공기 중의 총 부유분진 중 직경 10 ㎛ 이하의 먼지(PM10)로서 미세먼지를 흡입하면 하부 기관지 및 폐 실질까지 침착하여 호흡기계에 손상을 일으키고 기존 질환의 증상악화와 유병률 및 사망률을 증가시킨다.Fine dust is dust with a diameter of 10 ㎛ or less (PM10) among the total floating dust in the air. When fine dust is inhaled, it deposits in the lower bronchial tubes and lung parenchyma, causing damage to the respiratory system, worsening symptoms of existing diseases, and increasing morbidity and mortality rates. .
또한 미세먼지의 증가는 폐 기능의 감소와 유의한 연관관계를 나타내고 있으며, 미세먼지 노출 후 기관지 폐포 세척액에서 폐 대식세포, 호중구 및 림프구의 증가가 관찰되고, 폐 조직에 호중구의 증가와 기관조직에 림프구, 비만세포, IL-8 mRNA 발현의 증가를 가져온다고 알려져 있으나, 미세먼지로 인한 급성악화를 대상으로 하는 약물치료의 연구는 매우 부족한 실정으로 급성악화의 예방과 치료에 대한 연구가 요구되고 있으며, 더욱이 신뢰성 있는 천연물 유래 소재의 개발이 요구된다.In addition, the increase in fine dust shows a significant correlation with the decrease in lung function. After exposure to fine dust, an increase in lung macrophages, neutrophils, and lymphocytes was observed in bronchoalveolar lavage fluid, and an increase in neutrophils in lung tissue and tracheal tissue was observed. It is known to increase the expression of lymphocytes, mast cells, and IL-8 mRNA, but research on drug treatment targeting acute exacerbations caused by fine dust is very insufficient, and research on the prevention and treatment of acute exacerbations is required. , Furthermore, the development of reliable materials derived from natural products is required.
[선행특허문헌][Prior patent literature]
- 한국 등록특허 제10-1629706호 (2016.06.07. 등록)- Korean Patent No. 10-1629706 (registered on 2016.06.07)
- 한국 등록특허 제10-1791120호 (2017.10.23. 등록)- Korean Patent No. 10-1791120 (registered on October 23, 2017)
본 발명은 천연 복합 추출물을 함유한 조성물로서 체외 및 동물실험을 통해 미세먼지로 유발된 폐 손상을 개선할 수 있는 효과가 검증된 조성물을 제공하고자 한다.The present invention seeks to provide a composition containing natural complex extracts that has been proven effective in improving lung damage caused by fine dust through in vitro and animal experiments.
상기 과제를 해결하기 위하여 본 발명은, 지황, 상엽 및 맥문동의 복합 추출물을 유효성분으로 포함하는 미세먼지로 유발된 폐 손상을 개선하는 조성물을 제공한다.In order to solve the above problems, the present invention provides a composition that improves lung damage caused by fine dust, comprising a complex extract of Rehmannia glutinosa, Morifolia foliage, and Macunal sinensis as an active ingredient.
또한 상기 복합 추출물의 조성은 추출 대상물 기준으로 지황 45 내지 55 중량%, 상엽 15 내지 25 중량% 및 맥문동 25 내지 35 중량%인 것을 특징으로 하는 조성물을 제공한다.In addition, it provides a composition characterized in that the composition of the complex extract is 45 to 55% by weight of Rehmannia glutinosa, 15 to 25% by weight of upper leaves, and 25 to 35% by weight of Macmundong, based on the extraction target.
또한 상기 복합 추출물은 미세먼지로 자극시킨 폐포 대식세포(alveolar macrophage)에서 활성산소종(ROS), 염증성 사이토카인인 IL-6 및 TNF-α를 감소시키는 것을 특징으로 하는 조성물을 제공한다.In addition, the complex extract provides a composition that reduces reactive oxygen species (ROS) and inflammatory cytokines IL-6 and TNF-α in alveolar macrophages stimulated with fine dust.
또한 상기 복합 추출물은 미세먼지로 유발된 폐 손상 동물모델의 기관지 폐포 세척액(BALF)에서, 염증성 사이토카인인 CXCL-1, IL-17, MIP2 및 TNF-α를 감소시키고, 폐 조직에서 염증 관련 유전자인 CXCL-1, NOS-II, COX-2, TRAC, MIP2 및 TNF-α 발현을 감소시키고, 기관지염증 및 기침 관련 인자인 SDMA, MUC5AC, TRPV1 및 TRPA1 발현을 억제시키는 것을 특징으로 하는 조성물을 제공한다.In addition, the complex extract reduces inflammatory cytokines CXCL-1, IL-17, MIP2, and TNF-α in the bronchoalveolar lavage fluid (BALF) of an animal model of fine dust-induced lung damage, and reduces inflammation-related genes in lung tissue. Provides a composition that reduces the expression of CXCL-1, NOS-II, COX-2, TRAC, MIP2, and TNF-α and inhibits the expression of SDMA, MUC5AC, TRPV1, and TRPA1, which are factors related to bronchial inflammation and cough. do.
또한 상기 조성물은 약학적 조성물인 것을 특징으로 하는 조성물을 제공한다.Additionally, the composition provides a composition characterized in that it is a pharmaceutical composition.
또한 상기 조성물은 식품 조성물인 것을 특징으로 하는 조성물을 제공한다.Additionally, the composition provides a composition characterized in that it is a food composition.
본 발명에 따른 조성물은 지황, 상엽 및 맥문동의 복합 추출물을 함유하여 체외 실험 및 미세먼지로 유발된 폐 기능 저하 동물 모델에서 유의적인 폐 손상 개선 효과가 있음을 확인하였다.The composition according to the present invention was confirmed to have a significant lung damage improvement effect in in vitro experiments and in an animal model of lung function decline induced by fine dust, as it contains complex extracts of Rehmannia glutinosa, Morifolia foliage, and Macunaria sinensis.
도 1은 본 발명의 실험예에서 마우스 폐의 대식세포인 MH-S 세포주에 미세먼지 PM10-like(SRM®CZ120) 50 ㎍/㎖를 처리 후 ROS 분석 결과를 나타낸 그래프이다.
도 2는 본 발명의 실험예에서 마우스 폐의 대식세포인 MH-S 세포주에 미세먼지 PM10-like (50㎍/㎖) 처리를 하였을 때, inflammatory cytokine인 IL-6와 TNF-α 생산량을 분석한 결과를 나타낸 그래프이다.
도 3은 본 발명의 실험예에서 미세먼지(PM10+DEP) 동물모델 실험 종료 후 BAL 총 세포수 및 lung 총 세포수를 분석한 결과를 나타낸 그래프이다.
도 4는 본 발명의 실험예에서 미세먼지(PM10+DEP) 동물모델 실험 종료 후 폐세척액(BALF)에서 염증성 사이토카인(CXCL-1(A), IL-17(B), MIP2(C) 및 TNF- α(D))을 ELISA로 측정 분석한 결과를 나타낸 그래프이다.
도 5는 본 발명의 실험예에서 미세먼지(PM10+DEP) 동물모델실험 종료 후 혈청(serum)에서 기도저항인자(SDMA, symmetric dimethylarginine)를 ELISA로 측정 분석한 결과를 나타낸 그래프이다.
도 6은 본 발명의 실험예에서 미세먼지(PM10+DEP) 동물모델실험 종료 후 폐조직에서 염증성 사이토카인 유전자(TNF-α(F), TARC(C), COX-2(A), NOS-II(E), MIP-2(B) 및 CXCL-1(D)) 발현을 QRT-PCR로 측정 분석한 결과를 나타낸 그래프이다.
도 7은 본 발명의 실험예에서 미세먼지(PM10D) 동물모델실험 종료 후 폐조직에서 신호전달 IRAK1 단백질 발현을 면역형광조직염색(Immune histology fluorescent, IHF)으로 측정 분석한 결과를 나타낸 사진이다.
도 8은 본 발명의 실험예에서 미세먼지(PM10D) 동물모델실험 종료 후 폐조직에서 신호전달 TNF-α 및 MCP-1 단백질 발현을 면역형광조직염색(Immune histology fluorescent, IHF)으로 측정 분석한 결과를 나타낸 사진이다.
도 9 내지 13은 본 발명의 실험예에서 미세먼지(PM10+DEP) 동물모델실험 종료 후 말초 혈액 단핵세포(peripheral blood mononuclear cell, PBMC)에 대하여 FACS 분석을 통하여 백혈구(lymphocytes, granulocyte) 세포의 빈도수(%)를 분석한 결과를 나타낸 그래프이다.
도 14 내지 19는 본 발명의 실험예에서 미세먼지(PM10+DEP) 동물모델실험 종료 후 폐 조직(Lung)에서 염증세포 FACS 분석 결과를 나타낸 그래프이다.
도 20 내지 24는 본 발명의 실험예에서 미세먼지(PM10+DEP) 동물모델실험 종료 후 폐 세척액(BALF)에서 염증세포 FACS 분석 결과를 나타낸 그래프이다.
도 25는 본 발명의 실험예에서 미세먼지(PM10+DEP) 동물모델실험 종료 후 폐조직(Lung)을 H&E 염색한 결과를 나타낸 사진이다.Figure 1 is a graph showing the results of ROS analysis after treating 50 μg/ml of fine dust PM10-like (SRM®CZ120) to MH-S cell line, which is a mouse lung macrophage cell, in an experimental example of the present invention.
Figure 2 shows the analysis of the production of inflammatory cytokines IL-6 and TNF-α when the MH-S cell line, which is a mouse lung macrophage, was treated with fine dust PM10-like (50㎍/㎖) in an experimental example of the present invention. This is a graph showing the results.
Figure 3 is a graph showing the results of analyzing the total number of BAL cells and the total number of lung cells after completion of the fine dust (PM10 + DEP) animal model experiment in an experimental example of the present invention.
Figure 4 shows inflammatory cytokines (CXCL-1 (A), IL-17 (B), MIP2 (C) and This is a graph showing the results of measuring TNF-α(D)) using ELISA.
Figure 5 is a graph showing the results of measuring and analyzing airway resistance factor (SDMA, symmetric dimethylarginine) in serum by ELISA after completion of the fine dust (PM10+DEP) animal model experiment in an experimental example of the present invention.
Figure 6 shows inflammatory cytokine genes (TNF-α (F), TARC (C), COX-2 (A), NOS- This is a graph showing the results of measuring and analyzing expression of II (E), MIP-2 (B), and CXCL-1 (D)) by QRT-PCR.
Figure 7 is a photograph showing the results of measuring and analyzing the signal transduction protein expression of IRAK1 in lung tissue using immunofluorescent tissue staining (IHF) after completion of the fine dust (PM10D) animal model experiment in an experimental example of the present invention.
Figure 8 shows the results of measuring and analyzing signaling TNF-α and MCP-1 protein expression in lung tissue using immunofluorescence staining (IHF) after the end of the fine dust (PM10D) animal model experiment in an experimental example of the present invention. This is a photo showing .
Figures 9 to 13 show the frequency of white blood cells (lymphocytes, granulocytes) through FACS analysis of peripheral blood mononuclear cells (PBMC) after completion of the fine dust (PM10+DEP) animal model experiment in the experimental example of the present invention. This is a graph showing the results of analyzing (%).
Figures 14 to 19 are graphs showing the results of FACS analysis of inflammatory cells in lung tissue (Lung) after completion of the fine dust (PM10+DEP) animal model experiment in an experimental example of the present invention.
Figures 20 to 24 are graphs showing the results of FACS analysis of inflammatory cells in lung lavage fluid (BALF) after completion of the fine dust (PM10+DEP) animal model experiment in an experimental example of the present invention.
Figure 25 is a photograph showing the results of H&E staining of lung tissue (Lung) after completion of the fine dust (PM10+DEP) animal model experiment in an experimental example of the present invention.
이하 바람직한 실시예를 통하여 본 발명을 상세히 설명하기로 한다. 이에 앞서, 본 명세서 및 청구범위에 사용된 용어나 단어는 통상적이거나 사전적인 의미로 한정해서 해석되어서는 아니 되며, 발명자는 그 자신의 발명을 가장 최선의 방법으로 설명하기 위해 용어의 개념을 적절하게 정의할 수 있다는 원칙에 입각하여, 본 발명의 기술적 사상에 부합하는 의미와 개념으로 해석되어야만 한다. 따라서, 본 명세서에 기재된 실시예의 구성은 본 발명의 가장 바람직한 일실시예에 불과할 뿐이고 본 발명의 기술적 사상을 모두 대변하는 것은 아니므로, 본 출원시점에 있어서 이들을 대체할 수 있는 다양한 균등물과 변형예들이 있을 수 있음을 이해하여야 한다. 또한, 명세서 전체에서, 어떤 부분이 어떤 구성요소를 "포함"한다고 할 때, 이는 특별히 반대되는 기재가 없는 한, 다른 구성요소를 제외하는 것이 아니라 다른 구성요소를 더 포함할 수 있음을 의미한다.Hereinafter, the present invention will be described in detail through preferred embodiments. Prior to this, the terms or words used in this specification and claims should not be construed as limited to their usual or dictionary meanings, and the inventor should appropriately define the concept of terms in order to explain his or her invention in the best way. Based on the principle of definability, it must be interpreted with meaning and concept consistent with the technical idea of the present invention. Therefore, the configuration of the embodiments described in this specification is only one of the most preferred embodiments of the present invention and does not represent the entire technical idea of the present invention, so various equivalents and modifications can be substituted for them at the time of filing the present application. You must understand that there may be. In addition, throughout the specification, when a part is said to "include" a certain element, this means that it may further include other elements rather than excluding other elements, unless specifically stated to the contrary.
본 발명은 지황, 상엽 및 맥문동의 복합 추출물을 유효성분으로 포함하는 미세먼지로 유발된 폐 손상을 개선하는 조성물을 개시한다.The present invention discloses a composition that improves lung damage caused by fine dust, comprising a complex extract of Rehmannia glutinosa, Morifolia lily, and L. vulgaris as active ingredients.
상기 지황은 현삼과에 속하는 속하는 다년생 초본으로 그 뿌리와 뿌리줄기를 약으로 쓴다. 사물탕(四物湯)의 주요 약재로서 각종 만성병 중 몸이 허약하여 나타나는 내열(內熱), 인후건조(咽喉乾燥), 갈증 등의 증상에 쓰이고 있다.The above Rehmannia glutinosa is a perennial herb belonging to the Hyeonsam family, and its roots and rhizomes are used as medicine. It is the main medicinal ingredient in Samul-tang and is used to treat symptoms such as internal heat, dry throat, and thirst that appear due to weakness in the body among various chronic diseases.
또한 상기 상엽은 뽕나무과나무의 잎으로서 민간에서 약재로 이용 되어왔으며, 상엽에는 단백질, 아미노산, 비타민, 미네랄 및 다량의 식이섬유소뿐 아니라 다양한 생리활성물질을 함유하고 있다.In addition, the upper leaves are leaves of the Moraceae tree and have been used as a medicinal herb in the private sector. The upper leaves contain not only proteins, amino acids, vitamins, minerals, and a large amount of dietary fiber, but also various physiologically active substances.
또한 상기 맥문동은 백합과의 식물로서, 항산화 작용이 있고, 관상동맥의 혈류량 촉진과 심장 근육의 허혈증에 대한 보호작용이 현저하며, 진정작용을 나타내는 것으로 보고되고 있고, 혈당을 내리며 백색 포도상구균과 대장균으로부터 항균작용을 나타내는 것으로 알려져 있다.In addition, the above-mentioned MacMoondong is a plant of the Liliaceae family, has an antioxidant effect, has a remarkable effect on promoting blood flow in the coronary artery and protecting against ischemia of the heart muscle, and is reported to have a sedative effect, lowers blood sugar, and kills white Staphylococcus aureus and Escherichia coli. It is known to exhibit antibacterial activity.
본 발명에서 상기 복합 추출물의 형태나 성상에는 제한이 없으며, 용액, 농축물일 수도 있고, 추출물 제조에 사용된 용매를 제거한 고형분 또는 분말일 수도 있다.In the present invention, there is no limitation on the form or properties of the complex extract, and it may be a solution, a concentrate, or a solid or powder obtained by removing the solvent used in preparing the extract.
상기 복합 추출물은 용매 추출법을 사용하여 제조될 수 있다. 용매 추출법을 이용한 추출물 제조에 사용되는 추출 용매는 물이 선택되고, 바람직하게는 열수추출법이 사용될 수 있다. 추출 온도는 80 내지 100℃일 수 있고, 바람직하게는 90 내지 10℃, 더욱 바람직하게는 95 내지 100℃일 수 있다. 이때, 제조 수율을 더욱 고려하여 물량은 5 내지 30배수 및 추출 시간은 1 내지 10시간으로 하여 추출이 수행되고, 바람직하게는 물량 5 내지 20배수, 추출 시간 1 내지 8시간, 더욱 바람직하게는 물량 8 내지 15배수, 추출 시간 2 내지 5시간으로 하여 추출이 수행될 수 있다.The complex extract can be prepared using a solvent extraction method. The extraction solvent used to prepare the extract using the solvent extraction method is water, and preferably, the hot water extraction method can be used. The extraction temperature may be 80 to 100°C, preferably 90 to 10°C, and more preferably 95 to 100°C. At this time, in further consideration of the manufacturing yield, extraction is performed at a volume of 5 to 30 times and an extraction time of 1 to 10 hours, preferably at a volume of 5 to 20 times and an extraction time of 1 to 8 hours, more preferably at a volume of 5 to 20 times. Extraction can be performed with 8 to 15 multiples and an extraction time of 2 to 5 hours.
본 발명에서 상기 복합 추출물의 배합비는 용매 추출 시 투입되는 함량 기준으로 지황 45 내지 55 중량%, 상엽 15 내지 25 중량% 및 맥문동 25 내지 35 중량%일 수 있고, 바람직하게는 지황 47 내지 53 중량%, 상엽 17 내지 23 중량% 및 맥문동 27 내지 33 중량%일 수 있고, 더욱 바람직하게는 지황 49 내지 51 중량%, 상엽 19 내지 21 중량% 및 맥문동 29 내지 31 중량%일 수 있다.In the present invention, the mixing ratio of the complex extract may be 45 to 55% by weight of Rehmannia glutinosa, 15 to 25% by weight of upper leaves, and 25 to 35% by weight of Macmundong, based on the amount added during solvent extraction, and preferably 47 to 53% by weight of Rehmannia glutinosa. , it may be 17 to 23% by weight of upper leaves and 27 to 33% by weight of Macmundong, and more preferably, it may be 49 to 51% by weight of Rehmannia glutinosa, 19 to 21% by weight of upper leaves, and 29 to 31% by weight of Macmundong.
상기 복합 추출물은 미세먼지로 유발된 폐 손상을 개선하는 효과를 구현하며, 예컨대, 체외 실험으로서 미세먼지로 자극시킨 폐포 대식세포(alveolar macrophage)에서 활성산소종(ROS), 염증성 사이토카인인 IL-6 및 TNF-α를 감소시키고, 동물 실험으로서 미세먼지로 유발된 폐 손상 동물모델의 기관지 폐포 세척액(BALF)에서, 염증성 사이토카인인 CXCL-1, IL-17, MIP2 및 TNF-α를 감소시키고, 폐 조직에서 염증 관련 유전자인 CXCL-1, NOS-II, COX-2, TRAC, MIP2 및 TNF-α 발현을 감소시키고, 기관지염증 및 기침 관련 인자인 SDMA, MUC5AC, TRPV1 및 TRPA1 발현을 억제시키는 것을 확인하였다.The complex extract has the effect of improving lung damage caused by fine dust. For example, in an in vitro experiment, reactive oxygen species (ROS) and IL-, an inflammatory cytokine, were detected in alveolar macrophages stimulated with fine dust. 6 and TNF-α, and in animal experiments, it reduces inflammatory cytokines CXCL-1, IL-17, MIP2, and TNF-α in the bronchoalveolar lavage fluid (BALF) of an animal model of fine dust-induced lung damage. , reduces the expression of inflammation-related genes CXCL-1, NOS-II, COX-2, TRAC, MIP2, and TNF-α in lung tissue, and suppresses the expression of SDMA, MUC5AC, TRPV1, and TRPA1, factors related to bronchial inflammation and cough. confirmed.
본 발명에 따른 조성물은 약학적 조성물 또는 식품 조성물의 형태로 제공된다.The composition according to the invention is provided in the form of a pharmaceutical composition or a food composition.
상기 약학적 조성물은 상기 유효성분 이외에 약학적으로 허용되는 담체를 포함할 수 있으며, 이러한 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리 돈, 셀룰로스, 물, 시럽, 메틸셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등 을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약학적 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. 적합한 약학적 으로 허용되는 담체 및 제제는 레밍턴의 약학적 과학(Remington's Pharmaceutical Sciences, 19th ed., 1995) 에 상세히 기재되어 있다.The pharmaceutical composition may include a pharmaceutically acceptable carrier in addition to the active ingredient, and such carriers are commonly used in formulations, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, Calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and minerals. Includes, but is not limited to, oil, etc. In addition to the above ingredients, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).
본 발명에 따른 약학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다. 한편, 본 발명의 약학 조성물의 투여량은 바람직하게는 1일 당 0.0001 내지 100 mg/kg(체중)이다. 본 발명의 약학적 조성물은 경구 또는 비경구로 투여할 수 있으며, 비경구 투여의 경우, 피부에 국소적으로 도포, 정맥 내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있다. 본 발명의 약학 조성물이 항산화, 주름개 선 및 피부재생의 효과를 나타내는 점을 감안하면, 경구투여 또는 피부에 국소적으로 도포되어 이루어지는 것이 바람직하다.The appropriate dosage of the pharmaceutical composition according to the present invention varies depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. may be prescribed. Meanwhile, the dosage of the pharmaceutical composition of the present invention is preferably 0.0001 to 100 mg/kg (body weight) per day. The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered topically on the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc. . Considering that the pharmaceutical composition of the present invention exhibits anti-oxidation, wrinkle improvement, and skin regeneration effects, it is preferably administered orally or topically applied to the skin.
본 발명의 조성물에 포함되는 유효성분의 농도는 치료 목적, 환자의 상태, 필요기간 등을 고려하여 결정할 수 있으며 특정 범위의 농도로 한정되지 않는다.The concentration of the active ingredient included in the composition of the present invention can be determined considering the purpose of treatment, patient condition, required period, etc., and is not limited to a specific concentration range.
본 발명의 약학적 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있 는 방법에 따라, 약학적으로 허용되는 담체 또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 주사제, 크림, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 및 카타플라스마제 중에서 선택된 어느 하나의 제형으로 제조될 수도 있 다. 상기 조성물이 피부외용제로 사용하는 경우, 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연 화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 또는 비이온형 유화제, 충전제, 금속이온봉쇄제 및 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 또는 친유성 활성제, 지질 소낭 또는 피부용 외용제에 통상적으로 사용되는 임의의 다른 성분과 같은 피 부 과학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다. 또한 상기 성분들은 피부 과학분야에서 일반 적으로 사용되는 양으로 도입될 수 있다.The pharmaceutical composition of the present invention is prepared in unit dosage form by formulating using a pharmaceutically acceptable carrier or excipient according to a method that can be easily performed by a person skilled in the art. Alternatively, it can be manufactured by placing it in a multi-capacity container. At this time, the formulation may be manufactured as any one formulation selected from injections, creams, patches, sprays, ointments, warning agents, lotions, liniment agents, pasta agents, and cataplasma agents. When the composition is used as an external skin agent, it may additionally contain fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, and water. , ionic or non-ionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles, or commonly used in external preparations for the skin. It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients. Additionally, the ingredients may be introduced in amounts commonly used in the field of dermatology.
또한 상기 식품 조성물은 기능성 식품, 영양 보조제, 건강 식품, 식품 첨가제 등의 모든 형태를 포함한다. 상기 유형의 식품 조성물은 당 업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다.Additionally, the food composition includes all forms such as functional foods, nutritional supplements, health foods, and food additives. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
예를 들면, 건강 식품으로는 상기 조성물 자체를 차, 주스 및 드링크의 형태로 제조하여 음용하도록 하거나, 과립화, 캡슐화 및 분말화하여 섭취할 수 있다.For example, as a health food, the composition itself can be prepared and consumed in the form of tea, juice, and drinks, or can be consumed by granulating, encapsulating, and powdering.
또한, 기능성 식품으로는 음료(알콜성 음료 포함), 과실 및 그의 가공식품(예: 과일통조림, 병조림, 잼, 마말레 이드 등), 어류, 육류, 및 그 가공식품(예: 햄, 소시지 콘비프 등), 빵류 및 면류(예: 우동, 메밀국수, 라면, 스파게티, 마카로니 등), 과즙, 각종 드링크, 쿠키, 엿, 유제품(예: 버터, 치즈 등), 식용식물유지, 마아가린, 식물성 단백질, 레토르트 식품, 냉동식품, 각종 조미료(예: 된장, 간장, 소스 등) 등에 추출물을 첨가하여 제조할 수 있다.In addition, functional foods include beverages (including alcoholic beverages), fruits and their processed foods (e.g. canned fruit, bottled foods, jam, marmalades, etc.), fish, meat, and their processed foods (e.g. ham, sausages, corned beef, etc.) etc.), bread and noodles (e.g. udon, buckwheat noodles, ramen, spaghetti, macaroni, etc.), fruit juice, various drinks, cookies, taffy, dairy products (e.g. butter, cheese, etc.), edible vegetable oil, margarine, vegetable protein, It can be manufactured by adding extracts to retort foods, frozen foods, and various seasonings (e.g., soybean paste, soy sauce, sauce, etc.).
또한, 본 발명의 조성물을 식품 첨가제의 형태로 사용하기 위해서는 분말 또는 농축액 형태로 제조하여 사용할 수 있다.Additionally, in order to use the composition of the present invention in the form of a food additive, it can be prepared and used in the form of a powder or concentrate.
본 발명의 식품 조성물 중 상기 추출물의 바람직한 함량은 식품 조성물 총 중량에 대하여 0.001 내지 50% 일 수 있으며, 바람직하게는 0.1 내지 50%, 더욱 바람직하게는 1 내지 20% 범위로 함유될 수 있다.The preferred content of the extract in the food composition of the present invention may be 0.001 to 50%, preferably 0.1 to 50%, and more preferably 1 to 20%, based on the total weight of the food composition.
이하, 구체적인 실험예를 들어 본 발명을 보다 상세히 설명한다.Hereinafter, the present invention will be described in more detail using specific experimental examples.
복합 추출물 제조Complex extract preparation
하기 표 1의 조성(단위: 중량%)으로 지황(한약인 주식회사, 한국), 상엽(한약인 주식회사, 한국)및 맥문동(한약인 주식회사, 한국)을 정제수 10배수로 100℃에서 3시간 동안 추출을 진행하였다. 추출액을 80 mesh 망에 여과한 후 60℃가 될 때까지 냉각하고, 냉각된 추출액을 65℃에서 2시간 동안 농축하여 복합 추출물을 제조하였다.With the composition (unit: weight %) shown in Table 1 below, Rehmannia glutinosa (Han Yak-in Co., Ltd., Korea), Sanyeop (Han Yak-in Co., Ltd., Korea) and Macmundong (Han Yak-in Co., Ltd., Korea) were extracted with 10 times purified water at 100°C for 3 hours. proceeded. The extract was filtered through an 80 mesh mesh, cooled to 60°C, and the cooled extract was concentrated at 65°C for 2 hours to prepare a composite extract.
(RML_C1)Manufacturing Example 1
(RML_C1)
(RML_C2)Production example 2
(RML_C2)
(RML_C3)Production example 3
(RML_C3)
(RML_C4)Production example 4
(RML_C4)
실험방법Experiment method
(1) 세포배양 및 미세먼지 처리(1) Cell culture and fine dust treatment
호흡기관의 대식세포 세포주인 Alveolar macrophage(MH-S) 세포에서 미세먼지(PM10)로 자극시키고 실험물질을 처리하여 ROS FACS 분석 및 IL-6, TNF-α ELISA 측정을 수행하였다.Alveolar macrophage (MH-S) cells, a macrophage cell line of the respiratory tract, were stimulated with fine dust (PM10) and treated with test substances, and ROS FACS analysis and IL-6 and TNF-α ELISA measurements were performed.
(2) 동물모델 효능평가(2) Animal model efficacy evaluation
1) 생쥐 및 표준 미세먼지(PM10D) 적용1) Application of mice and standard fine dust (PM10D)
7주령 수컷 Balb/c 마우스를 사용하고, 표준 미세먼지(PM10)를 적용한 실험적 동물모델로서, DEP(diesel exhaust particles, 디젤연소분진), 표준 미세먼지(PM10-like, ERM-CZ120) 동물모델을 구축 및 제작하였다.As an experimental animal model using 7-week-old male Balb/c mice and applying standard fine dust (PM10), DEP (diesel exhaust particles) and standard fine dust (PM10-like, ERM-CZ120) animal models were used. Built and manufactured.
2) 호흡기 손상 동물 모델 제작2) Creation of respiratory injury animal model
호흡기 손상 미세먼지(PM10)에 각각 DEP를 혼합한 4 mg/ml 미세먼지 혼합물(PM10D)을 Alum(aluminium hydroxide)에 희석시켜 INT(Intra-Nazal-Tracheal) injection 방법을 이용하여 3일 간격으로 3회(약물투여 3일 후, 6일 후, 9일 후 intra-nasaltracheal injection) 기도를 통해 폐로 직접 주입하는 동물모델을 제작하고, 최종 미세먼지(PM10D) 주입 3일 후 희생시켰다.Respiratory damage fine dust (PM10) mixed with DEP at 4 mg/ml fine dust mixture (PM10D) was diluted in Alum (aluminium hydroxide) and administered 3 times at 3-day intervals using the INT (Intra-Nazal-Tracheal) injection method. An animal model was created in which the drug was injected directly into the lungs through the trachea (intra-nasaltracheal injection 3 days, 6 days, and 9 days after drug administration), and sacrificed 3 days after the final injection of fine dust (PM10D).
3) 복합 추출물 농도 및 양성대조약물 투여3) Complex extract concentration and positive control drug administration
복합 추출물은 200 ㎎/㎏ 및 100 ㎎/㎏ 농도로, 양성대조군으로 dexamethasone(3 ㎎/㎏)을 11일간 매일 오전 11시에 경구 투여하였다.The composite extract was administered at a concentration of 200 mg/kg and 100 mg/kg, and as a positive control, dexamethasone (3 mg/kg) was orally administered every day at 11 am for 11 days.
4) 폐 손상 유발 확인4) Confirmation of lung damage
기관지 폐포 세척액(BALF)을 분리하여 염증 관련 면역세포의 발현을 FACS로 분석하고, 염증세포수, FACS 분석, MUC5AC, IL(Interleukin)-1β, IL-4, IL-6, IL-13, IL-17, IFN(interferon)-γ, eotaxin, KC(keratinocyte chemoattractant), MCP(monocyte chemotactic protein)-1, MIP(macrophage inflammatory protein)-1α 및 MUC5AC의 발현을 ELISA로 분석하여 미세먼지 농도별 처리에 따른 폐 손상 유발 정도를 평가하였다. 또한 Diff-Quik 용액을 이용하여 Cytospin에 의한 호중구 분석을 수행하였고, 일반혈액검사, 혈청생화학검사 및 혈액 내 IgE 및 SDMA ELISA 측정을 통해 폐 손상과의 연관성을 평가하였고, 기도(trachea) 및 폐(lung) 조직의 H&E, M-T, PAS 및 AB-PAS 염색을 통하여 폐포 손상, 세포 침윤, collagen 침착 등을 계량화하여 폐 손상 정도를 평가하였다. 또한 폐 조직에서 IHF를 이용하여 IRAK-1, CD11b, TNF-α 및 MCP-1의 발현 변화를 탐색하였다.Bronchoalveolar lavage fluid (BALF) was separated and the expression of inflammation-related immune cells was analyzed by FACS, inflammatory cell count, FACS analysis, MUC5AC, IL (Interleukin)-1β, IL-4, IL-6, IL-13, IL -17, the expression of interferon (IFN)-γ, eotaxin, KC (keratinocyte chemoattractant), MCP (monocyte chemotactic protein)-1, MIP (macrophage inflammatory protein)-1α, and MUC5AC were analyzed by ELISA for treatment according to fine dust concentration. The degree of lung damage induced was evaluated. In addition, neutrophil analysis was performed using Cytospin using Diff-Quik solution, and the correlation with lung damage was evaluated through general blood tests, serum biochemistry tests, and IgE and SDMA ELISA measurements in the blood, and the correlation with lung damage was evaluated in trachea and lungs ( The degree of lung damage was evaluated by quantifying alveolar damage, cell infiltration, and collagen deposition through H&E, M-T, PAS, and AB-PAS staining of lung tissue. Additionally, changes in the expression of IRAK-1, CD11b, TNF-α, and MCP-1 were explored in lung tissue using IHF.
실험결과 Experiment result
(1) 미세먼지(PM10) 유도 in vitro 복합 추출물 항염 효과(1) Fine dust (PM10)-induced in vitro complex extract anti-inflammatory effect
1) ROS 생성량 분석1) Analysis of ROS production amount
마우스 폐의 대식세포인 MH-S 세포주에 미세먼지 PM10-like(SRM®CZ120) 50 ㎍/㎖를 처리 후 ROS 분석 결과를 도 1에 나타내었다.The results of ROS analysis after treatment of 50 μg/ml of fine dust PM10-like (SRM ® CZ120) in MH-S cell line, which is a mouse lung macrophage, are shown in Figure 1.
도 1을 참조하면, 제조예 2(RML_C2)에 따른 복합 추출물을 100, 200 및 400 ㎍/㎖ 처리했을 때 ROS가 대조군(PM10-like_CTL)에 비하여 통계학적으로 유의성 있게 농도 의존적으로 43.7%(p<0.001), 56.1%(p<0.001) 및 61.6%(p<0.001) 이상 감소하였다. 즉, 제조예 2(RML_C2)에 따라 지황 50 중량%, 상엽 20 중량% 및 맥문동 30 중량% 비율로 복합 추출할 경우 이상적인 혼합 비율(RML_2C-Opt.)임을 확인할 수 있었다.Referring to Figure 1, when the complex extract according to Preparation Example 2 (RML_C2) was treated at 100, 200, and 400 ㎍/㎖, ROS was statistically significantly decreased by 43.7% (p) in a concentration-dependent manner compared to the control group (PM10-like_CTL). <0.001), decreased by more than 56.1% (p<0.001) and 61.6% (p<0.001). That is, according to Preparation Example 2 (RML_C2), it was confirmed that the ideal mixing ratio (RML_2C-Opt.) was obtained when complex extraction was performed at a ratio of 50% by weight of Rehmannia glutinosa, 20% by weight of Sangyeop, and 30% by weight of Maekmundong.
2) 염증성 사이토카인(Inflammatory Cytoine) 측정 2) Measurement of inflammatory cytokines
마우스 폐의 대식세포인 MH-S 세포주에 미세먼지 PM10-like (50㎍/㎖) 처리를 하였을 때, inflammatory cytokine인 IL-6와 TNF-α 생산량을 분석한 결과를 도 2에 나타내었다.When the MH-S cell line, a mouse lung macrophage cell, was treated with fine dust PM10-like (50 μg/ml), the results of analyzing the production of inflammatory cytokines IL-6 and TNF-α are shown in Figure 2.
도 2를 참조하면, 제조예 2(RML_C2)에 따른 복합 추출물을 100, 200 및 400 ㎍/㎖ 처리했을 때 IL-6와 TNF-α 생산량이 대조군(PM10-like_CTL)에 비하여 통계학적으로 유의성 있게 농도 의존적으로, IL-6 생산량은 32.0%(p<0.05), 45.0%(p<0.01) 및 56.8%(p<0.001) 감소하였고, TNF-a 생산량은 30.8%(p<0.001), 38.0%(p<0.001) 및 59.4%(p<0.001) 감소하였다. 즉, 제조예 2(RML_C2)에 따라 지황 50 중량%, 상엽 20 중량% 및 맥문동 30 중량% 비율로 복합 추출할 경우 이상적인 혼합 비율(RML_2C-Opt.)임을 확인할 수 있었다. Referring to Figure 2, when the complex extract according to Preparation Example 2 (RML_C2) was treated with 100, 200, and 400 ㎍/㎖, IL-6 and TNF-α production was statistically significantly higher than that of the control group (PM10-like_CTL). Concentration-dependently, IL-6 production decreased by 32.0% (p<0.05), 45.0% (p<0.01) and 56.8% (p<0.001), and TNF-a production decreased by 30.8% (p<0.001) and 38.0%. (p<0.001) and decreased by 59.4% (p<0.001). That is, according to Preparation Example 2 (RML_C2), it was confirmed that the ideal mixing ratio (RML_2C-Opt.) was obtained when complex extraction was performed at a ratio of 50% by weight of Rehmannia glutinosa, 20% by weight of Sangyeop, and 30% by weight of Maekmundong.
(2) 복합 추출물의 미세먼지(PM10D) 노출에 대한 호흡기 보호/개선 동물모델 효능평가(2) Evaluation of efficacy of composite extract in animal model for respiratory protection/improvement against exposure to fine dust (PM10D)
미세먼지(PM10+DEP) 호흡기 손상 동물모델에서 복합 추출물의 투여량 설정 및 경구투여로 효능평가를 하기 위하여 과립구(Neutrophil)와 호산구(Eosinophil)의 선택적 침윤 변화, 체액성, 세포매개 면역 및 점막면역 기능 분석, 염증 관련 유전자 발현 및 병리조직검사를 이용한 후보물질의 호흡기 보호 및 개선 효능평가를 진행하였다. 미세먼지(PM10D) 노출에 의한 호흡기 손상 동물제작에 사용된 시약과 미세먼지(PM10D) 노출에 의한 호흡기 손상 동물모델 디자인을 하기 표 2 및 3에 각각 정리하였다.In order to determine the dosage and evaluate efficacy through oral administration of the composite extract in an animal model of fine dust (PM10+DEP) respiratory damage, changes in selective infiltration of granulocytes (Neutrophils) and eosinophils (Eosinophils), humoral, cell-mediated immunity, and mucosal immunity We conducted an evaluation of the respiratory protection and improvement efficacy of candidate substances using functional analysis, inflammation-related gene expression, and histopathological examination. The reagents used to produce animals with respiratory damage due to exposure to fine dust (PM10D) and the design of the animal model for respiratory damage due to exposure to fine dust (PM10D) are summarized in Tables 2 and 3, respectively.
효능평가 항목은 다음과 같다.Efficacy evaluation items are as follows.
- BALF: 염증세포수, FACS 분석, MUC5AC, Cytokine류- BALF: Number of inflammatory cells, FACS analysis, MUC5AC, Cytokines
- 혈액: 혈구분석, 혈액임상학적 지표, IgE, IL-6, IL-17, SDMA ELISA 측정- Blood: blood cell analysis, blood clinical indicators, IgE, IL-6, IL-17, SDMA ELISA measurement
- 조직검사: 기도(trachea) 및 폐(lung)의 H&E, PAS 염색- Biopsy: H&E, PAS staining of trachea and lung
- Lung: 유전자 발현(CCR3, IL-15, IL-13, MUC5AC, eotaxin, TARC, TNF-α 등)- Lung: Gene expression (CCR3, IL-15, IL-13, MUC5AC, eotaxin, TARC, TNF-α, etc.)
- Lung: IHF를 이용하여 IRAK-1과 CD11b, TNF-α 및 MCP-1의 발현 변화 탐색- Lung: Exploring changes in expression of IRAK-1, CD11b, TNF-α, and MCP-1 using IHF
1) BAL과 lung 총 세포수 분석1) BAL and lung total cell count analysis
미세먼지(PM10+DEP) 동물모델실험 종료 후 BAL 총 세포수 및 lung 총 세포수를 분석한 결과를 도 3에 나타내었다.The results of analyzing the total number of BAL cells and total lung cells after completion of the fine dust (PM10+DEP) animal model experiment are shown in Figure 3.
도 3을 참조하면, 정상군(Balb/c_Nr)에 비하여 대조군 PM10D_CTL)이 유의성 있게 BAL 세포수의 증가를 나타내었다(p<0.01). 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏, 100 ㎎/㎏, p<0.01)은 대조군(PM10D_CTL)에 비하여 유의성 있게 감소하였다. 폐 조직에서 총 폐 세포수는 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)이 2배 이상 유의성 있게 Lung 세포수의 증가를 나타내었다(p<0.01). 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏ p<0.01, 100 ㎎/㎏)은 대조군(PM10D_CTL)에 비하여 유의성 있게 감소하였다. Referring to Figure 3, compared to the normal group (Balb/c_Nr), the control group (PM10D_CTL) showed a significant increase in the number of BAL cells (p<0.01). The positive control group (Dexamethasone, 3 mg/kg) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg, 100 mg/kg, p<0.01) significantly decreased compared to the control group (PM10D_CTL). did. In lung tissue, the total number of lung cells in the control group (PM10D_CTL) showed a significant increase of more than two times compared to the normal group (Balb/c_Nr) (p<0.01). The positive control group (Dexamethasone, 3 mg/kg) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg p<0.01, 100 mg/kg) significantly decreased compared to the control group (PM10D_CTL). .
2) 기관지 폐포세척액(BAL fluid; BALF)의 염증성 사이토카인 분석2) Analysis of inflammatory cytokines in bronchoalveolar lavage fluid (BAL fluid; BALF)
미세먼지(PM10+DEP) 동물모델실험 종료 후 폐 세척액(BALF)에서 염증성 사이토카인(CXCL-1(A), IL-17(B), MIP2(C) 및 TNF-α(D))을 ELISA로 측정 분석한 결과를 도 4에 나타내었다.After completing the fine dust (PM10+DEP) animal model experiment, ELISA was performed on inflammatory cytokines (CXCL-1 (A), IL-17 (B), MIP2 (C), and TNF-α (D)) in lung lavage fluid (BALF). The results of the measurement analysis are shown in Figure 4.
도 4를 참조하면, 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)이 유의성 있게 염증성 사이토카인 생산량이 증가하는 것으로 나타났다(p<0.001). 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏)은 대조군(PM10D_CTL)에 비하여 유의성 있게 농도 의존적으로 감소되었다(p<0.01)(도 4, A 내지 D 참조). 또한 제조예 2에 따른 복합 추출물(RML_2C-Opt.)(100 ㎎/㎏)에서 IL-17(B)와 TNF-α(D)는 대조군(PM10D_CTL)에 비하여 유의성 있게 감소되었다(p<0.05)(도 4, B 및 D 참조).Referring to Figure 4, the control group (PM10D_CTL) showed a significant increase in inflammatory cytokine production compared to the normal group (Balb/c_Nr) (p<0.001). The positive control group (Dexamethasone, 3 mg/kg) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg) showed a significant concentration-dependent decrease compared to the control group (PM10D_CTL) (p<0.01) (See Figure 4, A to D). In addition, IL-17 (B) and TNF-α (D) in the complex extract (RML_2C-Opt.) (100 mg/kg) according to Preparation Example 2 were significantly reduced compared to the control group (PM10D_CTL) (p<0.05) (See Figure 4, B and D).
3) 혈액 중 기관지 폐기능 지표(SDMA)와 폐 조직 기침 관련 유전자(MUC5AC, TRPV1 및 TRPA1) 분석3) Analysis of bronchial lung function index (SDMA) in blood and lung tissue cough-related genes (MUC5AC, TRPV1, and TRPA1)
미세먼지(PM10+DEP) 동물모델실험 종료 후 혈청(serum)에서 기도저항인자(SDMA, symmetric dimethylarginine)를 ELISA로 측정 분석한 결과를 도 5A에 나타내었다.The results of measuring and analyzing airway resistance factor (SDMA, symmetric dimethylarginine) in serum by ELISA after completing the fine dust (PM10+DEP) animal model experiment are shown in Figure 5A.
도 5A를 참조하면, 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)이 약 30.8% 이상 SDMA 수준이 유의성 있게 증가하였다(p<0.001). 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏)은 대조군(PM10D_CTL)에 비하여 유의성 있게 감소되었다(p<0.01).Referring to Figure 5A, compared to the normal group (Balb/c_Nr), the SDMA level in the control group (PM10D_CTL) significantly increased by about 30.8% or more (p<0.001). The positive control group (Dexamethasone, 3 mg/kg) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg) were significantly reduced compared to the control group (PM10D_CTL) (p<0.01).
폐 조직에서 기침(cough) 관련 유전자 발현을 측정 분석한 결과를 도 5B 내지 5D에 나타내었다.The results of measuring cough-related gene expression in lung tissue are shown in Figures 5B to 5D.
도 5B 내지 5D를 참조하면, 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)이 기침(cough) 관련 유전자(MUC5AC, TRPV1 및 TRPA1) mRNA 발현이 유의성 있게 증가하였다(p<0.05, p<0.01). 양성대조군(Dexamethasone, 3 ㎎/㎏, p<0.05, p<0.01)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏, p<0.01)은 대조군(PM10D_CTL)에 비하여 유의성 있게 농도 의존적으로 유전자 발현이 감소되었다.Referring to Figures 5B to 5D, compared to the normal group (Balb/c_Nr), the mRNA expression of cough-related genes (MUC5AC, TRPV1, and TRPA1) in the control group (PM10D_CTL) was significantly increased (p<0.05, p<0.01). ). The positive control group (Dexamethasone, 3 mg/kg, p<0.05, p<0.01) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg, p<0.01) compared to the control group (PM10D_CTL). Gene expression was significantly reduced in a concentration-dependent manner.
4) 폐 조직 염증성 사이토카인 유전자 발현 분석(QRT-PCR)4) Lung tissue inflammatory cytokine gene expression analysis (QRT-PCR)
미세먼지(PM10+DEP) 동물모델실험 종료 후 폐 조직에서 염증성 사이토카인 유전자(TNF-α(F), TARC(C), COX-2(A), NOS-II(E), MIP-2(B) 및 CXCL-1(D)) 발현을 QRT-PCR로 측정 분석한 결과를 도 6에 나타내었다.After completing the fine dust (PM10+DEP) animal model experiment, inflammatory cytokine genes (TNF-α (F), TARC (C), COX-2 (A), NOS-II (E), MIP-2 ( B) and CXCL-1(D)) expression was measured and analyzed by QRT-PCR, and the results are shown in Figure 6.
도 6을 참조하면, 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)에서 2배 이상 염증성 사이토카인 유전자 발현이 유의성 있게 증가하였다(p<0.001). 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏)은 대조군(PM10D_CTL)에 비하여 유의성 있게 농도 의존적으로 감소되었다.Referring to Figure 6, inflammatory cytokine gene expression was significantly increased by more than two times in the control group (PM10D_CTL) compared to the normal group (Balb/c_Nr) (p<0.001). The positive control group (Dexamethasone, 3 mg/kg) and the complex extract (RML_2C-Opt.) administered group (200 mg/kg) according to Preparation Example 2 showed a significant concentration-dependent decrease compared to the control group (PM10D_CTL).
제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(100 ㎎/㎏)에서는 NOS-II(E)와 TARC(C) mRNA 유전자 발현이 대조군(PM10D_CTL)에 비하여 유의성 있게 감소되었으나, COX-2(A), MIP-2(B), CXCL-1(D) 및 TNF-α(F) mRNA 유전자 발현은 대조군(PM10D_CTL)에 비하여 감소 경향을 나타냈으나 유의성은 나타나지 않았다.In the group administered (100 mg/kg) the complex extract (RML_2C-Opt.) according to Preparation Example 2, NOS-II (E) and TARC (C) mRNA gene expression was significantly decreased compared to the control group (PM10D_CTL), but COX-2 (A), MIP-2 (B), CXCL-1 (D), and TNF-α (F) mRNA gene expression showed a tendency to decrease compared to the control group (PM10D_CTL), but no significance was observed.
5) 폐 조직 신호전달 IRAK-1 및 CD11b 단백질 발현 분석(IHF)5) Lung tissue signaling IRAK-1 and CD11b protein expression analysis (IHF)
미세먼지(PM10D) 동물모델실험 종료 후 폐 조직에서 신호전달 IRAK1 단백질 발현을 면역형광조직염색(Immune histology fluorescent, IHF)으로 측정 분석한 결과를 도 7에 나타내었다.After completion of the fine dust (PM10D) animal model experiment, the expression of the signaling protein IRAK1 in lung tissue was measured and analyzed using immunofluorescent staining (Immune histology fluorescent, IHF), and the results are shown in Figure 7.
도 7을 참조하면, 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)에서 현저하게 IRAK-1 단백질 발현 증가를 나타내었다. 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏)은 대조군(PM10D_CTL)에 비하여 농도 의존적으로 유의성 있게 감소되었다(도 7, A 및 B 참조). 또한 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)에서 현저하게 CD11b 단백질 발현 증가를 나타내었다. 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏ p<0.05, 100 ㎎/㎏, p<0.01)은 대조군(PM10D_CTL)에 비하여 농도 의존적으로 유의성 있게 감소되었다(도 7, C 및 D 참조).Referring to Figure 7, IRAK-1 protein expression was significantly increased in the control group (PM10D_CTL) compared to the normal group (Balb/c_Nr). The positive control group (Dexamethasone, 3 mg/kg) and the complex extract (RML_2C-Opt.) administered group (200 mg/kg) according to Preparation Example 2 were significantly reduced in a concentration-dependent manner compared to the control group (PM10D_CTL) (Figure 7, A and B). Additionally, CD11b protein expression was significantly increased in the control group (PM10D_CTL) compared to the normal group (Balb/c_Nr). The positive control group (Dexamethasone, 3 mg/kg) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg p<0.05, 100 mg/kg, p<0.01) compared to the control group (PM10D_CTL). It was significantly reduced in a concentration-dependent manner (see Figure 7, C and D).
6) 폐 조직 신호전달 TNF-α 및 MCP-1 단백질 발현 분석(IHF)6) Analysis of lung tissue signaling TNF-α and MCP-1 protein expression (IHF)
미세먼지(PM10D) 동물모델실험 종료 후 폐 조직에서 신호전달 TNF-α 및 MCP-1 단백질 발현을 면역형광조직염색(Immune histology fluorescent, IHF)으로 측정 분석한 결과를 도 8에 나타내었다.After completion of the fine dust (PM10D) animal model experiment, the expression of signaling TNF-α and MCP-1 proteins in lung tissue was measured and analyzed using immunofluorescence staining (IHF), and the results are shown in Figure 8.
도 8을 참조하면, 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)에서 현저하게 TNF-α 단백질 발현이 증가를 나타내었다. 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏ p<0.05, 100 ㎎/㎏, p<0.01)은 대조군(PM10D_CTL)에 비하여 농도 의존적으로 유의성 있게 감소되었다(도 8, A 및 B 참조). 또한 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)에서 현저하게 MCP-1 단백질 발현 증가를 나타내었다(도 8, C 참조). 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏ p<0.001, 100 ㎎/㎏, p<0.05)은 대조군(PM10D_CTL)에 비하여 농도 의존적으로 유의성 있게 감소되었다(도 8, C 및 D 참조).Referring to Figure 8, TNF-α protein expression was significantly increased in the control group (PM10D_CTL) compared to the normal group (Balb/c_Nr). The positive control group (Dexamethasone, 3 mg/kg) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg p<0.05, 100 mg/kg, p<0.01) compared to the control group (PM10D_CTL). It was significantly reduced in a concentration-dependent manner (see Figure 8, A and B). Additionally, MCP-1 protein expression was significantly increased in the control group (PM10D_CTL) compared to the normal group (Balb/c_Nr) (see Figure 8, C). The positive control group (Dexamethasone, 3 mg/kg) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg p<0.001, 100 mg/kg, p<0.05) compared to the control group (PM10D_CTL). It was significantly reduced in a concentration-dependent manner (see Figure 8, C and D).
7) PBMC에서 총 백혈구(leucocytes) 세포빈도수 분석7) Analysis of total leucocytes cell frequency in PBMC
미세먼지(PM10+DEP) 동물모델실험 종료 후 말초 혈액 단핵세포(peripheral blood mononuclear cell, PBMC)에 대하여 FACS 분석을 통하여 백혈구(lymphocytes, granulocyte) 세포의 빈도수(%)를 분석한 결과를 도 9 내지 13에 나타내었다.Figures 9 to 9 show the results of analyzing the frequency (%) of white blood cells (lymphocytes, granulocytes) through FACS analysis of peripheral blood mononuclear cells (PBMC) after the end of the fine dust (PM10+DEP) animal model experiment. Shown in 13.
도 9 내지 13을 참조하면, 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)에서 lymphocytes, neutrophils, CD3+ T cells 및 CD4+ & CD8+ T helper 세포 빈도수(%)가 감소를 나타내었다. 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏, 100 ㎎/㎏)은 대조군(PM10D_CTL)에 비하여 lymphocytes, CD3+ T cells, CD4+ & CD8+ T helper 세포 빈도수(%)가 농도 의존적으로 증가되었다(p<0.01, p<0.001). 또한 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)에서 neutrophils, CD4+CD69+ cells 및 CD3+CD49b+ NK cells 빈도수(%)가 감소를 나타내었다.Referring to Figures 9 to 13, compared to the normal group (Balb/c_Nr), the frequency (%) of lymphocytes, neutrophils, CD3+ T cells, and CD4+ & CD8+ T helper cells in the control group (PM10D_CTL) was decreased. The positive control group (Dexamethasone, 3 mg/kg) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg, 100 mg/kg) had lymphocytes, CD3+ T cells, CD4+ compared to the control group (PM10D_CTL). & CD8+ T helper cell frequency (%) increased in a concentration-dependent manner (p<0.01, p<0.001). Additionally, compared to the normal group (Balb/c_Nr), the frequency (%) of neutrophils, CD4+CD69+ cells, and CD3+CD49b+ NK cells was decreased in the control group (PM10D_CTL).
8) 폐 조직(Lung) 염증세포 FACS 분석8) Lung inflammatory cell FACS analysis
미세먼지(PM10+DEP) 동물모델실험 종료 후 폐 조직(Lung)에서 염증세포 FACS 분석 결과를 하기 표 4, 도 14 내지 19에 나타내었다.The results of FACS analysis of inflammatory cells in lung tissue after completion of the fine dust (PM10+DEP) animal model experiment are shown in Table 4 and Figures 14 to 19 below.
표 4, 도 14 내지 19를 참조하면, 폐 조직(Lung)에서 염증활성 총 절대세포수(lymphocytes No. 도 14B), neutrophils 절대세포수(도 14B), eosinophils 절대세포수(도 14D), CD4+ & CD8+ absolute No.(도 15), CD62L-CD44high+ absolute No.(도 17), CD21/CD35+B220+ absolute No.(도 18) 및 Gr-1+/CD11b+ absolute No.(도 19)를 산출한 결과, 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)이 염증활성 총 절대세포수(CD4+ absolute No., neutrophils 절대세포수, Gr-1+/CD11b+ absolute No., CD3+/CD19+ absolute No., CD21/CD35+B220+ absolute No. 및 CD62L-CD44high+ absolute No.)가 유의성 있게 증가한 것으로 나타났다. 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏, 100 ㎎/㎏)은 대조군(PM10D_CTL)에 비하여 염증활성 총 절대세포수(CD4+ absolute No., neutrophils 절대세포수, CD62L-CD44+ absolute No., Gr-1+/CD11b+ absolute No., CD3+/CD19+ absolute No., CD21/CD35+B220+ absolute No.)가 유의성 있게 농도 의존적으로 감소되었다(도 14 내지 19 참조).Referring to Table 4 and Figures 14 to 19, the total absolute number of inflammatory cells in lung tissue (lymphocytes No. Figure 14B), absolute cell number of neutrophils (Figure 14B), absolute cell number of eosinophils (Figure 14D), CD4+ & CD8+ absolute No. (Figure 15), CD62L-CD44high+ absolute No. (Figure 17), CD21/CD35+B220+ absolute No. (Figure 18), and Gr-1+/CD11b+ absolute No. (Figure 19) As a result, compared to the normal group (Balb/c_Nr), the control group (PM10D_CTL) had a higher inflammatory activity total absolute cell count (CD4+ absolute No., neutrophils absolute cell count, Gr-1+/CD11b+ absolute No., CD3+/CD19+ absolute No., CD21/CD35+B220+ absolute No. and CD62L-CD44high+ absolute No.) were found to be significantly increased. The positive control group (Dexamethasone, 3 mg/kg) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg, 100 mg/kg) showed a total absolute absolute cell count of inflammatory activity compared to the control group (PM10D_CTL). CD4+ absolute No., neutrophils absolute cell count, CD62L-CD44+ absolute No., Gr-1+/CD11b+ absolute No., CD3+/CD19+ absolute No., CD21/CD35+B220+ absolute No.) decreased significantly in a concentration-dependent manner. (see FIGS. 14 to 19).
9) 폐 세척액(BALF) 염증세포 FACS 분석9) FACS analysis of lung lavage fluid (BALF) inflammatory cells
미세먼지(PM10+DEP) 동물모델실험 종료 후 폐 세척액(BALF)에서 염증세포 FACS 분석 결과를 하기 표 5, 도 20 내지 24에 나타내었다.The results of FACS analysis of inflammatory cells in lung lavage fluid (BALF) after completion of the fine dust (PM10+DEP) animal model experiment are shown in Table 5 and Figures 20 to 24.
표 5, 도 20 내지 24를 참조하면, 폐 세척액(BALF)에서 염증활성 총 절대세포수(lymphocytes No., 도 20B), neutrophils 절대세포수(도 20B), eosinophils 절대세포수(도 20C), CD4+ & CD8+ absolute No.(도 21), CD4+/CD69+ absolute No.(도 22), CD62L-CD44high+ absolute No.(도 23) 및 Gr-1+/CD11b+ absolute No.(도 24)를 산출한 결과, 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)이 염증활성 총 절대세포수(CD4+ absolute No., neutrophils 절대세포수, Gr-1+/CD11b+ absolute No., CD4+/CD69+ absolute No. 및 CD62L-CD44+ absolute No.)가 유의성 있게 증가한 것으로 나타났다. 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏, 100 ㎎/㎏)은 대조군(PM10D_CTL)에 비하여 염증활성 총 절대세포수(CD4+ absolute No., neutrophils 절대세포수, CD62L-CD44+ absolute No. 및 Gr-1+/CD11b+ absolute No.)가 대조군(PM10D_CTL)에 비하여 유의성 있게 농도 의존적으로 감소되었다(도 20 내지 24 참조).Referring to Table 5 and Figures 20 to 24, the total absolute number of inflammatory cells (lymphocytes No., Figure 20B), absolute number of neutrophils (Figure 20B), absolute number of eosinophils (Figure 20C) in lung lavage fluid (BALF), Results of calculating CD4+ & CD8+ absolute No. (Figure 21), CD4+/CD69+ absolute No. (Figure 22), CD62L-CD44high+ absolute No. (Figure 23), and Gr-1+/CD11b+ absolute No. (Figure 24) , Compared to the normal group (Balb/c_Nr), the control group (PM10D_CTL) had inflammatory activity total absolute cell count (CD4+ absolute No., neutrophils absolute cell count, Gr-1+/CD11b+ absolute No., CD4+/CD69+ absolute No., and CD62L). -CD44+ absolute No.) was found to have significantly increased. The positive control group (Dexamethasone, 3 mg/kg) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg, 100 mg/kg) showed a total absolute absolute cell count of inflammatory activity compared to the control group (PM10D_CTL). CD4+ absolute No., neutrophils absolute cell count, CD62L-CD44+ absolute No., and Gr-1+/CD11b+ absolute No.) were significantly decreased in a concentration-dependent manner compared to the control group (PM10D_CTL) (see Figures 20 to 24).
10) 폐 조직(Lung tissue) 분석10) Lung tissue analysis
미세먼지(PM10+DEP) 동물모델실험 종료 후 폐 조직(Lung)을 H&E 염색한 결과를 도 25에 나타내었다.The results of H&E staining of lung tissue (Lung) after completion of the fine dust (PM10+DEP) animal model experiment are shown in Figure 25.
도 25를 참조하면, 정상군(Balb/c_Nr)에 비하여 대조군(PM10D_CTL)에서 기관지(brochia) 주변에 미세먼지(PM10 & DEP)의 침착이 뚜렷하게 증가를 나타내었고, 기도의 두께가 크게 증가하였으며, 기관지(airway) 주변에 염증면역세포의 침윤과 과립구세포(neutrophils, eosinophils) 및 활성화된 대식세포들로 인하여 염증이 심화되어 폐포세포 파괴가 진행된 것으로 나타났다. 폐포세포 파괴 정도는 콜라겐 침착(collagen deposition)으로 관찰하기 위하여 Masson Trichrome(M-T) 염색으로 structure 부분의 기도(tracheol)와 폐포(alveolar) 및 세포 부분의 염증(inflammatory)과 혈액(blood) 세포의 침윤 정도를 관찰할 수 있다. 또한 대조군(PM10D_CTL)에서는 기관지(airway) 주변에 점액질을 분비하는 배상세포(goblet cell)(PAS 염색)가 많이 분포하였다. 양성대조군(Dexamethasone, 3 ㎎/㎏)과 제조예 2에 따른 복합 추출물(RML_2C-Opt.) 투여군(200 ㎎/㎏)은 대조군(PM10D_CTL)에 비하여 기관지(airway) 주변에 미세먼지(PM10 & DEP)의 침착이 뚜렷하게 감소하였고, 기도의 두께가 정상군에 가깝게 감소를 나타내어 기관지(airway) 주변에 염증면역세포의 침윤과 과립구세포(neutrophils, eosinophils) 및 활성화된 대식세포들이 크게 감소하였고, 콜라겐 침착(collagen deposition)은 Masson Trichrome(M-T) 염색으로 structure 부분의 기도(tracheol)와 폐포(alveolar), 기관지(airway) 주변에 점액질을 분비하는 배상세포(goblet cell) 및 세포 부분의 염증(inflammatory)과 혈액(blood) 세포의 침윤정도도 정상군에 가깝게 억제되었다.Referring to Figure 25, compared to the normal group (Balb/c_Nr), the control group (PM10D_CTL) showed a clear increase in the deposition of fine dust (PM10 & DEP) around the bronchia, and the thickness of the airway significantly increased. It was found that the inflammation intensified due to the infiltration of inflammatory immune cells, neutrophils, eosinophils, and activated macrophages around the bronchi (airways), leading to destruction of alveolar cells. To observe the degree of alveolar cell destruction through collagen deposition, Masson Trichrome (M-T) staining was used to detect inflammation and blood cell infiltration in the tracheal and alveolar parts of the structure and in the cellular part. The degree can be observed. Additionally, in the control group (PM10D_CTL), many goblet cells (PAS staining) that secrete mucus were distributed around the airways. The positive control group (Dexamethasone, 3 mg/kg) and the group administered the complex extract (RML_2C-Opt.) according to Preparation Example 2 (200 mg/kg) had higher levels of fine dust (PM10 & DEP) around the bronchial tubes than the control group (PM10D_CTL). ) deposition was clearly reduced, and the thickness of the airway decreased close to that of the normal group. Infiltration of inflammatory immune cells around the bronchi (airway), granulocyte cells (neutrophils, eosinophils), and activated macrophages were significantly reduced, and collagen deposition was observed. (collagen deposition) is a Masson Trichrome (M-T) staining that shows inflammation in goblet cells and cells that secrete mucus around the tracheol, alveolar, and bronchi of the structure. The degree of blood cell infiltration was also suppressed, close to that of the normal group.
이하에서는 본 발명에 따른 복합 추출물을 유효성분으로 함유하는 식품 조성물 및 약학적 조성물의 적용예를 설명하나, 이에 한정되는 것은 아니다.Hereinafter, application examples of food compositions and pharmaceutical compositions containing the complex extract according to the present invention as an active ingredient will be described, but are not limited thereto.
적용예 1: 액상 조성물 제조Application Example 1: Preparation of liquid composition
하기 표 6에서는 상술한 본 발명에 따른 복합 추출물을 유효성분으로 함유하는 액상 조성물의 조성을 예시하고 있다. 액상 조성물은 통상의 액상 조성물 제조방법에 따라 정제수에 각각의 하기 성분들을 가하여 용해시키고 레몬향을 적량 가한 후 하기 성분들을 혼합한 다음 정제수를 가하여 전체 100 ㎖로 조절한 후 갈색병에 충진 및 멸균시켜 제조될 수 있다.Table 6 below illustrates the composition of a liquid composition containing the complex extract according to the present invention described above as an active ingredient. The liquid composition is prepared by adding and dissolving each of the following ingredients in purified water according to a typical liquid composition manufacturing method, adding an appropriate amount of lemon flavor, mixing the following ingredients, adding purified water to adjust the total volume to 100 ml, and then filling and sterilizing it in a brown bottle. can be manufactured.
적용예 2: 건강기능식품 제조Application example 2: Manufacturing health functional foods
하기 표 7에서는 상술한 본 발명에 따른 복합 추출물을 유효성분으로 함유하는 건강기능식품 조성을 나타내고 있다. 하기 조성에서 비타민 및 미네랄 혼합물의 조성비는 비교적 건강기능식품에 적합한 성분을 바람직한 적용예로 혼합 조성한 것을 나타내고 있으나, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능식품 제조방법에 따라 각 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능식품 조성물 제조에 사용할 수 있다.Table 7 below shows the composition of a health functional food containing the complex extract according to the present invention described above as an active ingredient. In the composition below, the composition ratio of the vitamin and mineral mixture indicates that ingredients relatively suitable for health functional foods are mixed as a preferred application example, but the mixing ratio may be modified arbitrarily, and each component is prepared according to the usual health functional food manufacturing method. After mixing, granules are prepared and can be used to manufacture a health functional food composition according to a conventional method.
적용예 3: 건강 음료 제조Application example 3: Healthy beverage production
하기 표 8에서는 상술한 본 발명에 따른 복합 추출물을 유효성분으로 함유하는 기능성 건강 음료 조성을 나타내고 있다. 건강 음료 제조는 통상의 건강음료 제조방법에 따라 예컨대, 하기 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 후 냉장 보관하여 사용할 수 있다. 하기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였으나, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Table 8 below shows the composition of a functional health drink containing the complex extract according to the present invention described above as an active ingredient. Health drink production follows a typical health drink production method, for example, mixing the following ingredients, stirring and heating at 85°C for about 1 hour, filtering the resulting solution, placing it in a sterilized 2-liter container, sealing, sterilizing, and refrigerating. It can be stored and used. The following composition ratio is a mixture of ingredients that are relatively suitable for beverages of choice as a preferred example, but the mixing ratio may be arbitrarily modified depending on regional and ethnic preferences such as demand class, demand country, and intended use.
적용예 4: 산제 제조Application example 4: Powder manufacturing
하기 표 9에서는 상술한 본 발명에 따른 복합 추출물을 유효성분으로 함유하는 산제 조성을 나타내고 있다. 산제는 하기 성분들을 혼합하고 기밀포에 충진하여 제조될 수 있다.Table 9 below shows the composition of a powder containing the complex extract according to the present invention described above as an active ingredient. Powder can be prepared by mixing the following ingredients and filling them in an airtight bubble.
적용예 5: 정제 제조Application Example 5: Tablet manufacturing
하기 표 10에서는 상술한 본 발명에 따른 복합 추출물을 유효성분으로 함유하는 정제 조성을 나타내고 있다. 정제는 하기 성분들을 혼합한 후 통상의 정제 제조방법에 따라 타정하여 제조될 수 있다.Table 10 below shows the tablet composition containing the complex extract according to the present invention described above as an active ingredient. Tablets can be manufactured by mixing the following ingredients and compressing them according to a conventional tablet manufacturing method.
적용예 6: 캅셀제 제조Application example 6: Capsule production
하기 표 11에서는 상술한 본 발명에 따른 복합 추출물을 유효성분으로 함유하는 캅셀제 조성을 나타내고 있다. 캅셀제는 통상의 캅셀제 제조방법에 따라 하기 성분들을 혼합하고 젤라틴 캡슐에 충전하여 제조될 수 있다.Table 11 below shows the composition of a capsule containing the complex extract according to the present invention described above as an active ingredient. Capsules can be manufactured by mixing the following ingredients and filling them into gelatin capsules according to a typical capsule manufacturing method.
적용예 7: 주사제 제조Application Example 7: Injection manufacturing
하기 표 12에서는 상술한 본 발명에 따른 복합 추출물을 유효성분으로 함유하는 주사제 조성을 나타내고 있다. 주사제는 통상의 주사제 제조방법에 따라 1앰플당(2 ㎖) 하기 성분 함량으로 제조될 수 있다.Table 12 below shows the composition of an injection containing the complex extract according to the present invention described above as an active ingredient. Injections can be prepared with the following ingredients per ampoule (2 ml) according to a typical injection preparation method.
적용예 8: 액제 제조Application example 8: Liquid preparation
하기 표 13에서는 상술한 본 발명에 따른 복합 추출물을 유효성분으로 함유하는 액제 조성을 나타내고 있다. 액제는 통상의 액제 제조방법에 따라 정제수에 각각의 하기 성분들을 가하여 용해시키고 레몬향을 적량 가한 후 하기 성분들을 혼합한 다음 정제수를 가하여 전체 100 ㎖로 조절한 후 갈색병에 충진 및 멸균시켜 제조될 수 있다.Table 13 below shows the liquid composition containing the complex extract according to the present invention described above as an active ingredient. The liquid can be prepared by adding and dissolving each of the following ingredients in purified water according to a typical liquid preparation method, adding an appropriate amount of lemon flavor, mixing the following ingredients, adding purified water to adjust the total to 100 ml, and then filling and sterilizing it in a brown bottle. You can.
이상에서 설명한 본 발명의 바람직한 실시예들은 기술적 과제를 해결하기 위해 개시된 것으로, 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자라면 본 발명의 사상 및 범위 안에서 다양한 수정, 변경, 부가 등이 가능할 것이며, 이러한 수정 변경 등은 이하의 특허청구범위에 속하는 것으로 보아야 할 것이다.The preferred embodiments of the present invention described above were disclosed to solve technical problems, and those skilled in the art will be able to make various modifications, changes, additions, etc. within the spirit and scope of the present invention. , such modifications and changes should be regarded as falling within the scope of the patent claims below.
Claims (6)
상기 복합 추출물의 조성은 추출 대상물 기준으로 지황 47 내지 53 중량%, 상엽 17 내지 23 중량% 및 맥문동 27 내지 33 중량%인 것을 특징으로 하는 조성물.A composition that improves lung damage caused by fine dust, containing complex extracts of Rehmannia glutinosa, Morifolia, and Macunnialis as active ingredients,
A composition characterized in that the composition of the complex extract is 47 to 53% by weight of Rehmannia glutinosa, 17 to 23% by weight of sangyeop, and 27 to 33% by weight of Macmundong, based on the extraction object.
상기 복합 추출물은 미세먼지로 자극시킨 폐포 대식세포(alveolar macrophage)에서 활성산소종(ROS), 염증성 사이토카인인 IL-6 및 TNF-α를 감소시키는 것을 특징으로 하는 조성물.According to paragraph 1,
A composition characterized in that the complex extract reduces reactive oxygen species (ROS) and inflammatory cytokines IL-6 and TNF-α in alveolar macrophages stimulated with fine dust.
상기 복합 추출물은 미세먼지로 유발된 폐 손상 동물모델의 기관지 폐포 세척액(BALF)에서, 염증성 사이토카인인 CXCL-1, IL-17, MIP2 및 TNF-α를 감소시키고, 폐 조직에서 염증 관련 유전자인 CXCL-1, NOS-II, COX-2, TRAC, MIP2 및 TNF-α 발현을 감소시키고, 기관지염증 및 기침 관련 인자인 SDMA, MUC5AC, TRPV1 및 TRPA1 발현을 억제시키는 것을 특징으로 하는 조성물.According to paragraph 1,
The complex extract reduces inflammatory cytokines CXCL-1, IL-17, MIP2, and TNF-α in the bronchoalveolar lavage fluid (BALF) of an animal model of fine dust-induced lung damage, and reduces inflammation-related genes in lung tissue. A composition characterized by reducing the expression of CXCL-1, NOS-II, COX-2, TRAC, MIP2, and TNF-α, and inhibiting the expression of SDMA, MUC5AC, TRPV1, and TRPA1, which are factors related to bronchial inflammation and cough.
상기 조성물은 약학적 조성물인 것을 특징으로 하는 조성물.According to paragraph 1,
The composition is characterized in that it is a pharmaceutical composition.
상기 조성물은 식품 조성물인 것을 특징으로 하는 조성물.
According to paragraph 1,
The composition is characterized in that it is a food composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020210078558A KR102680125B1 (en) | 2021-06-17 | Composition for enhancing pulmonary function having extract of Rehmannia glutinosa Liboschitz var |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020210078558A KR102680125B1 (en) | 2021-06-17 | Composition for enhancing pulmonary function having extract of Rehmannia glutinosa Liboschitz var |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20220169024A KR20220169024A (en) | 2022-12-27 |
| KR102680125B1 true KR102680125B1 (en) | 2024-07-01 |
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