KR20200020210A - Composition for inhibition of neutrophil elastase comprising plant extract - Google Patents
Composition for inhibition of neutrophil elastase comprising plant extract Download PDFInfo
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- KR20200020210A KR20200020210A KR1020180095639A KR20180095639A KR20200020210A KR 20200020210 A KR20200020210 A KR 20200020210A KR 1020180095639 A KR1020180095639 A KR 1020180095639A KR 20180095639 A KR20180095639 A KR 20180095639A KR 20200020210 A KR20200020210 A KR 20200020210A
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- extract
- neutrophil elastase
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- plant
- disease
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Abstract
Description
본 발명은 식물 추출물을 함유하는 조성물에 관한 것으로서, 보다 상세하게는 호중구 엘라스타아제(neutrophil elastase)의 과도한 활성으로 인해 유발되는 다양한 질환의 예방 또는 치료에 유용하게 사용될 수 있는 식물 추출물을 함유하는 조성물에 관한 것이다.The present invention relates to a composition containing a plant extract, and more particularly, a composition containing a plant extract that can be usefully used for the prevention or treatment of various diseases caused by excessive activity of neutrophil elastase. It is about.
엘라스타아제는 사실상 모든 결합 조직 성분을 분해하는 능력을 갖는 체내에서 가장 파괴적인 효소 중 하나이다. 엘라스타아제에 의한 비조절 단백질 가수분해는 수많은 병리학적 상태와 연관된다. 세린 프로테아제의 키모트립신 수퍼패밀리(superfamily)의 구성원인 인간 호중구 엘라스타아제는 호중구의 일차 과립(아주르친화성 과립)에서 발견되는 세린 프로테아제 중 하나이다.Elastase is one of the most disruptive enzymes in the body with the ability to degrade virtually all connective tissue components. Unregulated proteolysis by elastase is associated with numerous pathological conditions. Human neutrophil elastase, a member of the chymotrypsin superfamily of serine proteases, is one of the serine proteases found in neutrophil primary granules (azurffinity granules).
호중구는 백혈구 중 가장 많은 비중을 차지하고 이동성이 높아 염증 반응에 매우 빠르게 반응하며, 다양한 효소들을 가지고 있는 3 종류의 과립을 방출하고, 그 중 호중구 엘라스타아제는 엘라스틴을 포함한 매우 다양한 단백질들을 분해할 수 있다. 특히 호중구 엘라스타아제는 생체내에서 콜라겐(collagen)-3, 콜라겐-4, 피브로넥틴(fibronectin), 라미닌(laminin), 데코린(decorin), 바이글리칸(biglycan) 등의 다양한 세포외 매트릭스 단백질을 분해하는 역할을 한다. 호중구 엘라스타아제의 주요한 세포내 생리학적 기능은 호중구에 의한 식세포작용으로 유입된 외래 유기 분자의 분해인 반면, 세포외 엘라스타아제에 대한 주요한 표적은 엘라스틴이다. 호중구 엘레스타아제는 거의 모든 세포외 매트릭스 및 중요 혈장 단백질을 분해하는 능력을 갖는다는 점에서 다른 프로테아제(예컨대, 프로테이나제 3)에 비해 독특하다.Neutrophils occupy the largest proportion of leukocytes and are highly mobile and respond very quickly to inflammatory reactions, releasing three types of granules with various enzymes, among which neutrophil elastase can break down a wide variety of proteins, including elastin. have. In particular, neutrophil elastase can be used in vivo to produce various extracellular matrix proteins such as collagen-3, collagen-4, fibronectin, laminin, decorin, and biglycan. Decomposes. The major intracellular physiological function of neutrophil elastase is the degradation of foreign organic molecules introduced into phagocytosis by neutrophils, while the major target for extracellular elastase is elastin. Neutrophil eletases are unique over other proteases (eg, proteinase 3) in that they have the ability to degrade almost all extracellular matrix and important plasma proteins.
호중구 엘라스타아제는 손상된 조직의 구조 단백질들의 분해를 통해 조직의 재건에 기여함으로써 인체 조직의 항상성 유지에 중요한 역할을 하고, 인체에 침투한 세균을 제거하는 방어기전에 기여하는 것으로 알려져 있다. 또한 다양한 사이토카인(cytokine)을 분비하여 상피세포에서의 IL-8 등의 발현을 촉진시키는 등의 염증 반응을 일으킨다.Neutrophil elastase plays an important role in maintaining homeostasis of human tissues by contributing to the reconstruction of tissues through the degradation of structural proteins of damaged tissues, and is known to contribute to the defense mechanism of removing bacteria that enter the human body. In addition, the secretion of various cytokines (cytokine) causes an inflammatory response such as promoting IL-8 expression in epithelial cells.
인간 호중구 엘라스타아제는 수많은 질환, 예컨대 성인 호흡 곤란 증후군(ARDS), 낭성 섬유증, 폐 기종, 만성 기관지염을 비롯한 기관지염, 기관지확장증, 만성 폐쇄성 폐 질환(COPD), 폐 고혈압증, 난치성 천식을 비롯한 천식, 비염, 건선, 허혈-재관류 손상, 류마티스성 관절염, 골관절염, 전신성 염증성 반응 증후군(SIRS), 만성 창상, 암, 아테롬성 동맥경화증, 소화성 궤양, 크론병, 궤양성 대장염 또는 위 점막 손상의 촉진 또는 악화와 연관되어 있다(특허문헌 1). 특히, 호중구 엘라스타아제는 염증 반응에 있어서 호중구 유입이 특징으로 나타나는 만성 호흡기 질환에서 핵심적인 역할을 하는 것으로 알려져 있으며, 담배 연기 노출에 의해 유도된 만성 폐쇄성 폐질환(chronic obstructive pulmonary disease, COPD)의 동물 모델에서 호중구 엘라스타아제의 억제제들이 질환 증상을 억제하는 결과를 보였다(비특허문헌 1). 또한, 호중구 엘라스타아제는 만성 폐쇄성 폐질환뿐만 아니라, 낭포성 섬유증, 급성 호흡 곤란 증후군, 기관지확장증, 폐기종, 폐렴 및 폐 섬유증 등과 같은 여러 가지 폐질환의 발병 기전에 관여하고 있다(비특허문헌 2).Human neutrophil elastase has numerous diseases, such as adult respiratory distress syndrome (ARDS), cystic fibrosis, pulmonary emphysema, bronchitis including chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD), pulmonary hypertension, asthma, including refractory asthma, Promoting or exacerbating rhinitis, psoriasis, ischemia-reperfusion injury, rheumatoid arthritis, osteoarthritis, systemic inflammatory response syndrome (SIRS), chronic wounds, cancer, atherosclerosis, peptic ulcer, Crohn's disease, ulcerative colitis or gastric mucosal injury It is related (patent document 1). In particular, neutrophil elastase is known to play a key role in chronic respiratory diseases characterized by neutrophil influx in the inflammatory response, and has been shown to affect chronic obstructive pulmonary disease (COPD) induced by cigarette smoke exposure. In animal models, inhibitors of neutrophil elastase have been shown to suppress disease symptoms (Non-Patent Document 1). In addition, neutrophil elastase is involved in the pathogenesis of various lung diseases such as cystic fibrosis, acute respiratory distress syndrome, bronchiectasis, emphysema, pneumonia and pulmonary fibrosis, as well as chronic obstructive pulmonary disease (Non-Patent Document 2). ).
아울러, 호중구 엘라스타아제는 폐 질환 외에도 급성 심근경색(myocardial infarction)에 이은 허혈성 조직 손상의 발생 및 심부전에 관여하고(특허문헌 1), 호중구 엘라스타아제 억제제의 투여가 알레르기성 비염, 천식, 아토피 피부염 및 수포성 천포창에서의 증상 개선 효과를 보였으며(비특허문헌 3 및 비특허문헌 4), 건선, 아토피 피부염, 접촉성 피부염 병변에서도 호중구 엘라스타아제의 활성이 크게 증가되어 있음이 보고된 바 있다(비특허문헌 5). 또한, 크론병, 궤양성 대장염, 과민성 대장 증후군의 진단마커로 사용할 수 있음이 알려져 있고(비특허문헌 6 및 비특허문헌 7). 동물모델에서 고지질 식이에 의한 비만이나 인슐린 저항성의 발생 과정에도 기여하는 것으로 밝혀졌으며(비특허문헌 8), 피부의 광노화 과정에서 발생하는 일광 탄력섬유증에도 관여하는 것이 보고된 바 있다(비특허문헌 9).In addition, neutrophil elastase is involved in the occurrence and heart failure of ischemic tissue damage following acute myocardial infarction in addition to pulmonary disease (Patent Document 1), and administration of neutrophil elastase inhibitors causes allergic rhinitis, asthma, atopy Symptoms were improved in dermatitis and bullous pemphigus (Non Patent Literature 3 and Non Patent Literature 4), and neutrophil elastase activity was reported to be significantly increased in psoriasis, atopic dermatitis, and contact dermatitis. There is (nonpatent literature 5). In addition, it is known that it can be used as a diagnostic marker for Crohn's disease, ulcerative colitis and irritable bowel syndrome (Non-Patent Document 6 and Non-Patent Document 7). Animal models have also been shown to contribute to the development of obesity and insulin resistance due to high-fat diets (Non-Patent Document 8), and has been reported to be involved in sunshine elastic fibrosis during photoaging of the skin (Non-Patent Documents). 9).
이러한 질환들은 호중구-매개성 염증 반응 및 호중구 엘라스타아제 등의 분해효소에 의한 조직 손상으로부터 기인하며, 이러한 반응의 결정 요인으로는 호중구 엘라스타아제를 억제할 수 있는 내분비성 엘라스타아제 억제단백질들(α1-안티트립신(α1-AT), 분비백혈구 프로테아제 억제제(SLPI) 및 프리-엘라핀 등)과의 밸런스가 중요한 인자인 것으로 여겨지고, 내분비성 안티프로테아제와 호중구 엘라스타아제의 불균형은 다양한 염증성 조직 손상을 유발시킬 수 있는 것으로 알려져 있다.These diseases are caused by neutrophil-mediated inflammatory reactions and tissue damage by degrading enzymes such as neutrophil elastase, and endogenous elastase inhibitors that can inhibit neutrophil elastase The balance between (α1-antitrypsin (α1-AT), secretory leukocyte protease inhibitors (SLPI), and pre-elapin, etc.) is believed to be an important factor, and the imbalance of endocrine antiproteases and neutrophil elastase is due to various inflammatory tissues. It is known to cause damage.
한편, 종래 호중구 엘라스타아제를 억제하기 위한 약물로는 치환된 바이사이클릭 디하이드로피리미디논, 2-피리돈 화합물 등의 소분자 화합물들이 공개되어 있으나(특허문헌 2 및 특허문헌 3), 다양한 종류의 천연 물질을 이용한 호중구 엘라스타아제 억제제에 대한 선행 연구는 거의 없는 실정이다.Meanwhile, as a drug for inhibiting neutrophil elastase, small molecule compounds such as substituted bicyclic dihydropyrimidinone and 2-pyridone compound are disclosed (Patent Document 2 and Patent Document 3), but various kinds There is very little previous research on neutrophil elastase inhibitors using natural substances.
본 발명은 다양한 천연물 유래의 추출물을 유효성분으로 함유하는 호중구 엘라스타아제의 활성과 연관된 질환의 치료용 조성물을 제공하는 것을 목적으로 한다.It is an object of the present invention to provide a composition for the treatment of diseases associated with the activity of neutrophil elastase containing extracts derived from various natural products as active ingredients.
상기 과제를 해결하기 위하여, 본 발명은 식물 추출물을 유효성분으로 함유하는 호중구 엘라스타아제의 활성과 연관된 질환의 치료용 조성물을 제공한다. 본 발명의 한 구현예에 따르면, 상기 조성물은 약학적 조성물 또는 건강식품 조성물의 형태일 수 있으나 이에 한정되는 것은 아니다.In order to solve the above problems, the present invention provides a composition for the treatment of diseases associated with the activity of neutrophil elastase containing a plant extract as an active ingredient. According to one embodiment of the invention, the composition may be in the form of a pharmaceutical composition or health food composition, but is not limited thereto.
본 발명의 바람직한 구현예에 따르면, 상기 호중구 엘라스타아제의 활성과 연관된 질환은 호중구 엘라스타아제의 과도한 활성으로 인해 발생하는 질환일 수 있고, 예컨대 성인 호흡 곤란 증후군(ARDS), 낭성 섬유증, 폐 기종, 만성 기관지염, 기관지확장증, 만성 폐쇄성 폐 질환(COPD), 폐 고혈압증, 천식, 비염, 건선, 허혈-재관류 손상, 류마티스성 관절염, 골관절염, 전신성 염증성 반응 증후군(SIRS), 만성 창상, 암, 아테롬성 동맥경화증, 소화성 궤양, 크론병, 궤양성 대장염 등일 수 있으나 이에 한정되는 것은 아니다.According to a preferred embodiment of the invention, the disease associated with the activity of neutrophil elastase may be a disease resulting from excessive activity of neutrophil elastase, such as adult respiratory distress syndrome (ARDS), cystic fibrosis, pulmonary emphysema , Chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD), pulmonary hypertension, asthma, rhinitis, psoriasis, ischemia-reperfusion injury, rheumatoid arthritis, osteoarthritis, systemic inflammatory response syndrome (SIRS), chronic wounds, cancer, atherosclerosis Sclerosis, peptic ulcer, Crohn's disease, ulcerative colitis, and the like, but is not limited thereto.
본 발명의 다른 구현예에 따르면, 상기 식물 추출물은 딸기 추출물, 메밀 추출물, 쌀보리 추출물, 찰수수 추출물, 율무 추출물, 기장 추출물, 백미 추출물, 참마 추출물, 팥 추출물 및 권백 추출물로 이루어진 군으로부터 선택되는 1종 이상일 수 있으나 이에 한정되는 것은 아니다.According to another embodiment of the present invention, the plant extract is one species selected from the group consisting of strawberry extract, buckwheat extract, rice barley extract, waxy water extract, yulmu extract, millet extract, white rice extract, yam extract, red beans extract, and baekbaek extract It may be more than, but is not limited thereto.
본 발명의 바람직한 구현예에 따르면, 상기 식물 추출물의 제조에 사용되는 추출용매는 물, 유기용매 또는 이들의 혼합물일 수 있고, 상기 유기용매는 알코올, 헥산, 에테르, 글리세롤, 프로필렌글리콜, 부틸렌글리콜, 에틸아세테이트, 메틸아세테이트, 디클로로메탄, 클로로포름, 벤젠, 또는 이들의 혼합용매일 수 있으나 이에 한정되는 것은 아니다.According to a preferred embodiment of the present invention, the extraction solvent used in the preparation of the plant extract may be water, an organic solvent or a mixture thereof, the organic solvent is alcohol, hexane, ether, glycerol, propylene glycol, butylene glycol , Ethyl acetate, methyl acetate, dichloromethane, chloroform, benzene, or a mixed solvent thereof, but is not limited thereto.
본 발명의 조성물은 호중구 엘라스타아제에 대한 억제 활성이 뛰어나므로, 호중구 엘라스타아제의 과도한 활성으로 인해 유발되는 질환들, 예컨대 성인 호흡 곤란 증후군(ARDS), 만성 폐쇄성 폐 질환(COPD) 등의 폐질환이나 비염, 건선, 허혈-재관류 손상 등과 같은 다양한 질환의 예방 또는 치료에 유용하게 사용될 수 있다.Since the composition of the present invention has excellent inhibitory activity against neutrophil elastase, lungs such as diseases caused by excessive activity of neutrophil elastase, such as adult respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD), etc. It can be usefully used for the prevention or treatment of various diseases such as disease, rhinitis, psoriasis, ischemia-reperfusion injury and the like.
도 1a 내지 도 1c는 본 발명에서 개시하고 있는 다양한 식물 추출물의 호중구 엘라스타아제 활성 억제 효과를 보여주는 웨스턴 블롯(Western blot) 전기영동 사진이다.1a to 1c are Western blot electrophoresis pictures showing the inhibitory effect of neutrophil elastase activity of various plant extracts disclosed in the present invention.
본 발명은 식물 추출물을 유효성분으로 함유하는 호중구 엘라스타아제의 활성과 연관된 질환의 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for the treatment of diseases associated with the activity of neutrophil elastase containing a plant extract as an active ingredient.
본 발명에 있어서, 상기 호중구 엘라스타아제의 활성과 연관된 질환은 호중구 엘라스타아제의 과도한 활성으로 인해 발생하는 질환들을 제한없이 포함하며, 예컨대 상기 질환은 성인 호흡 곤란 증후군(ARDS), 낭성 섬유증, 폐 기종, 만성 기관지염, 기관지확장증, 만성 폐쇄성 폐 질환(COPD), 폐 고혈압증, 천식, 비염, 건선, 허혈-재관류 손상, 류마티스성 관절염, 골관절염, 전신성 염증성 반응 증후군(SIRS), 만성 창상, 암, 아테롬성 동맥경화증, 소화성 궤양, 크론병, 궤양성 대장염으로부터 선택될 수 있으나 이에 한정되는 것은 아니다.In the present invention, diseases associated with the activity of neutrophil elastase include, without limitation, diseases resulting from excessive activity of neutrophil elastase, such as for example, adult respiratory distress syndrome (ARDS), cystic fibrosis, lung Emphysema, chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD), pulmonary hypertension, asthma, rhinitis, psoriasis, ischemia-reperfusion injury, rheumatoid arthritis, osteoarthritis, systemic inflammatory response syndrome (SIRS), chronic wounds, cancer, atherosclerosis Atherosclerosis, peptic ulcer, Crohn's disease, ulcerative colitis may be selected from, but is not limited thereto.
본 발명에 있어서, 상기 식물 추출물은 딸기 추출물, 메밀 추출물, 쌀보리 추출물, 찰수수 추출물, 율무 추출물, 기장 추출물, 백미 추출물, 참마 추출물, 팥 추출물 및 권백 추출물로 이루어진 군으로부터 선택되는 식물 추출물을 단독으로 또는 2종 이상 조합하여 사용될 수 있다.In the present invention, the plant extract is alone or a plant extract selected from the group consisting of strawberry extract, buckwheat extract, rice barley extract, waxy water extract, yulmu extract, millet extract, white rice extract, yam extract, red beans extract, and baekbaek extract It can be used in combination of two or more kinds.
본 발명에서 일컫는 "추출물"은 식물 원료로부터 임의의 방법으로 추출된 물질을 나타내는 것으로서, 이렇게 추출된 추출액, 이로부터 얻을 수 있는 농축액, 상기 농축액의 건조물, 분말, 또는 상기 추출액의 발효물 등을 제한 없이 모두 포함하는 의미로 사용된다. 상기 추출물은 식물 원료 또는 이의 건조물로부터 추출하여 얻을 수 있으며, 상기 추출물의 원료는 재배한 것 또는 시판되는 것 등을 제한 없이 사용할 수 있다.As used herein, the term "extract" refers to a material extracted from a plant raw material by any method, and limits the extract thus extracted, the concentrate obtained therefrom, the dried product of the concentrate, powder, or the fermentation product of the extract. It is used to include all without. The extract can be obtained by extracting from a plant raw material or its dried material, the raw material of the extract can be used without limitation, such as cultivated or commercially available.
상기 추출물을 식물 원료로부터 추출하여 수득할 때, 추출 방법으로는 용매 추출법, 초음파 추출법, 여과법 및 환류 추출법 등과 같이 종래 알려진 통상적인 추출 방법을 비제한적으로 사용할 수 있으며, 바람직하게는 용매 추출법이나 환류 추출법을 이용함으로써 제조할 수 있으나 이에 한정되는 것은 아니다. 상기 추출 과정은 수회 반복할 수 있으며, 이후에 농축 또는 동결건조 등의 단계를 추가적으로 거칠 수 있다. 구체적으로, 수득한 식물 추출물을 감압 농축하여 농축액을 얻고, 상기 농축액을 동결건조시킨 후 분쇄기를 이용하여 고농도의 식물 추출물 분말을 제조할 수 있다.When the extract is obtained by extracting from a plant raw material, conventional extraction methods such as solvent extraction, ultrasonic extraction, filtration and reflux extraction may be used as extraction methods without limitation, preferably solvent extraction or reflux extraction. It can be prepared by using, but is not limited thereto. The extraction process may be repeated several times, after which it may be further subjected to steps such as concentration or lyophilization. Specifically, the obtained plant extract may be concentrated under reduced pressure to obtain a concentrate, and the concentrate may be lyophilized to prepare a high concentration plant extract powder using a grinder.
상기 식물 추출물은 물, 유기용매 또는 이들의 혼합물을 추출용매로 하여 추출될 수 있다. 상기 유기용매는 알코올, 바람직하게는 C1-C4의 알코올, 헥산(n-헥산), 에테르, 글리세롤, 프로필렌글리콜, 부틸렌글리콜, 에틸아세테이트, 메틸아세테이트, 디클로로메탄, 클로로포름, 벤젠 및 이들의 혼합용매를 사용할 수 있으나 이에 한정되는 것은 아니다.The plant extract may be extracted using water, an organic solvent or a mixture thereof as an extractant. The organic solvent is alcohol, preferably C 1 -C 4 alcohol, hexane (n-hexane), ether, glycerol, propylene glycol, butylene glycol, ethyl acetate, methyl acetate, dichloromethane, chloroform, benzene and their A mixed solvent may be used, but is not limited thereto.
본 발명의 약학적 조성물 내에 2종 이상의 식물 추출물의 혼합물이 포함될 때, 해당 식물들을 개별적으로 추출한 추출물을 제조한 후 이를 조합해 사용할 수도 있고, 해당 식물들의 혼합물을 추출하여 사용할 수도 있으나 이에 한정되는 것은 아니다.When a mixture of two or more plant extracts is included in the pharmaceutical composition of the present invention, an extract obtained by separately extracting the corresponding plants may be prepared and used in combination, or a mixture of the corresponding plants may be extracted, but is not limited thereto. no.
상기 추출은 60℃ 내지 100℃의 온도에서 실시될 수 있고, 바람직하게는 65℃ 내지 95℃에서 실시될 수 있으며, 더욱 바람직하게는 70℃ 내지 90℃에서 실시될 수 있으나 이에 한정되는 것은 아니다. 상기 범위를 벗어나서 실시될 경우에는 해당 추출물의 호중구 엘라스타아제 억제 활성이 낮아질 수 있다.The extraction may be carried out at a temperature of 60 ℃ to 100 ℃, preferably may be carried out at 65 ℃ to 95 ℃, more preferably may be carried out at 70 ℃ to 90 ℃, but is not limited thereto. When carried out outside the above range, the neutrophil elastase inhibitory activity of the extract may be lowered.
상기 추출은 1시간 내지 20시간 동안 실시될 수 있고, 바람직하게는 2시간 내지 16시간 동안 실시될 수 있으며, 더욱 바람직하게는 3시간 내지 12시간 동안 실시될 수 있으나, 이에 한정하지 아니한다. 상기 범위를 벗어나서 실시될 경우에는 해당 추출물의 호중구 엘라스타아제 억제 활성이 낮아질 수 있다.The extraction may be carried out for 1 to 20 hours, preferably for 2 to 16 hours, more preferably for 3 to 12 hours, but is not limited thereto. When carried out outside the above range, the neutrophil elastase inhibitory activity of the extract may be lowered.
상기 추출은 1회 내지 8회 실시될 수 있고, 바람직하게는 1회 내지 6회 실시될 수 있으며, 더욱 바람직하게는 1회 내지 5회 실시될 수 있으나 이에 한정되는 것은 아니다. 상기 추출물은 각 추출에서 얻어진 단독 추출물 또는 각 추출에서 얻어진 추출물들의 혼합 추출물일 수 있고, 바람직하게는 각 추출에서 얻어진 추출물들의 혼합 추출물일 수 있다.The extraction may be performed once to eight times, preferably may be carried out once to six times, more preferably may be carried out once to five times, but is not limited thereto. The extract may be a single extract obtained from each extract or a mixed extract of extracts obtained from each extract, preferably a mixed extract of extracts obtained from each extract.
상기 식물 추출물은 호중구 엘라스타아제 억제 활성의 효과를 높이기 위하여 추가로 통상의 분획 공정을 수행할 수 있다. 예를 들면, 본 발명에 따른 식물 추출물을 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 얻은 분획물, 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등으로 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 활성 분획물도 본 발명의 식물 추출물의 범위 내에 포함된다. 상기 크로마토그래피는 컬럼 크로마토그래피일 수 있고, 예컨대 실리카겔, 세파덱스, LH-20, ODS 겔, RP-18, 폴리아미드, 도요펄(Toyopearl) 및 XAD 수지로 이루어진 군으로부터 선택된 충진제를 이용하는 컬럼 크로마토그래피를 수행하여 활성 분획물을 분리 및 정제할 수 있으며, 컬럼 크로마토그래피는 필요에 따라 적절한 충진제를 선택하여 수차례 실시할 수 있으나 이에 한정되는 것은 아니다. 상기 크로마토그래피를 사용함에 있어 용출 용매, 용출 속도 및 용출 시간은 본 기술분야의 통상의 기술자가 일반적으로 사용하는 용매, 속도 또는 시간 등을 적용할 수 있다.The plant extract may further perform a conventional fractionation process in order to increase the effect of neutrophil elastase inhibitory activity. For example, fractions obtained by passing a plant extract according to the present invention through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity). Active fractions obtained through various purification methods additionally carried out in the above are also included within the scope of the plant extracts of the present invention. The chromatography may be column chromatography, for example column chromatography using a filler selected from the group consisting of silica gel, Sephadex, LH-20, ODS gel, RP-18, polyamide, Toyopearl and XAD resin The active fraction can be separated and purified by performing the step, and column chromatography can be carried out several times by selecting an appropriate filler as necessary, but is not limited thereto. In using the chromatography, an elution solvent, an elution rate, and an elution time may be applied to a solvent, a rate, or a time generally used by those skilled in the art.
본 발명의 약학적 조성물은 상기 식물 추출물 이외에 본 발명이 목적으로 하는 효과를 손상시키지 않는 범위 내에서, 바람직하게는 상기 식물 추출물에 상승효과를 줄 수 있는 다른 성분 등을 추가로 함유할 수 있다. 예를 들면, 본 발명의 약학적 조성물은 상기 식물 추출물 이외에도 항산화제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제 또는 담체를 비제한적으로 포함할 수 있다.The pharmaceutical composition of the present invention may further contain, in addition to the above-mentioned plant extract, other ingredients that can give a synergistic effect to the plant extract, preferably within the range of not impairing the effect intended by the present invention. For example, the pharmaceutical composition of the present invention may include, but is not limited to, conventional adjuvants or carriers such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors in addition to the plant extract.
상기 약학적 조성물의 투여 경로는 구강, 정맥내, 근육내, 동맥내, 경피, 피하, 복강내, 비강내, 장관, 국소, 설하 또는 직장이 포함되고, 예컨대 도포에 의한 국부투여(topical application) 방식으로 적용될 수 있으나 이에 한정되는 것은 아니다. 상기 비경구는 피하, 피내, 정맥내, 근육내, 병소내 주사 또는 주입기술을 포함하지만 이에 한정되는 것은 아니다.Routes of administration of the pharmaceutical compositions include oral, intravenous, intramuscular, intraarterial, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual or rectal, for example topical application by application. It may be applied in a manner, but is not limited thereto. The parenteral includes, but is not limited to, subcutaneous, intradermal, intravenous, intramuscular, intralesional injection or infusion techniques.
본 발명의 약학적 조성물은 상기 식물 추출물에 추가로 동일 또는 유사한 기능을 나타내는 유효성분을 1종 이상 함유할 수 있다. 본 발명의 약학적 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀전, 시럽 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.The pharmaceutical composition of the present invention may further contain one or more active ingredients exhibiting the same or similar functions in addition to the plant extract. The pharmaceutical compositions of the present invention can be used in the form of oral dosage forms, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods.
경구 투여를 위한 고형제제에는 산제, 과립제, 정제, 캡슐제, 연질캅셀제, 환 등이 포함되고, 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있으나 이에 한정되는 것은 아니다. 비경구 투여를 위한 제제로는 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 멸균된 수용액, 액제, 비수성용제, 현탁제, 에멀전, 시럽, 좌제, 에어로졸 등의 외용제 및 멸균 주사제제의 형태로 제형화하여 사용될 수 있고, 바람직하게는 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 또는 카타플라스마제의 피부 외용 약학적 조성물을 제조하여 사용할 수 있으나 이에 한정되는 것은 아니다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브유와 같은 식물성유, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있고, 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있으나 이에 한저되는 것은 아니다.Solid preparations for oral administration include powders, granules, tablets, capsules, soft capsules, pills, and the like, and liquid preparations for oral administration include suspensions, solvents, emulsions, and syrups. In addition to water and liquid paraffin, which are diluents, various excipients may be included, such as but not limited to wetting agents, sweeteners, fragrances, and preservatives. Formulations for parenteral administration include powders, granules, tablets, capsules, sterile aqueous solutions, solutions, non-aqueous solutions, suspensions, emulsions, syrups, suppositories, aerosols, etc. It may be used in the form of a formulation, and preferably, an external skin pharmaceutical composition of a cream, a gel, a patch, a spray, an ointment, a warning, a lotion, a linen, a pasta, or a cataplasm may be prepared. It is not limited to this. As a non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, etc. may be used, and suppository bases such as witepsol, macrogol, and tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used, but are not limited thereto.
또한, 본 발명의 약학적 조성물은 방부제, 안정화제, 수화제 또는 유화 촉진제, 삼투압 조절을 위한 염 및/또는 완충제 등의 보조제 및 기타 치료적으로 유용한 물질을 추가로 함유할 수 있고, 통상적인 방법인 혼합, 과립화 또는 코팅 방법에 따라 제형화할 수 있으나 이에 한정되는 것은 아니다.In addition, the pharmaceutical composition of the present invention may further contain auxiliaries such as preservatives, stabilizers, hydrating or emulsifiers, salts and / or buffers for the control of osmotic pressure and other therapeutically useful substances, It may be formulated according to the mixing, granulation or coating method, but is not limited thereto.
본 발명의 약학적 조성물의 투여량은 개체의 연령, 체중, 일반적인 건강, 성별, 투여시간, 투여 경로, 배출률, 약물 배합 및 특정 질환의 중증을 포함한 여러 요인에 따라 다양하게 변할 수 있다. 또한, 본 발명의 약학적 조성물은 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다. 또한, 상기 약학적 조성물은 성인 기준으로 0.001 내지 100 ㎎/㎏ 범위 내의 투여량으로 투여될 수 있고, 상기 약학적 조성물이 외용제인 경우에는 성인기준으로 1.0 내지 3.0 ㎖의 양으로 1일 1회 내지 5회 도포하여 1개월 이상 계속하는 것이 좋으나, 상기 투여량은 본 발명의 범위를 한정하는 것은 아니다.The dosage of the pharmaceutical composition of the present invention may vary depending on several factors, including the age, body weight, general health, sex, time of administration, route of administration, rate of release, drug combination and severity of the particular disease of the individual. In addition, the pharmaceutical compositions of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers. In addition, the pharmaceutical composition may be administered in a dosage range of 0.001 to 100 mg / kg on an adult basis, and when the pharmaceutical composition is an external preparation once daily in an amount of 1.0 to 3.0 ml on an adult basis It is preferable to apply 5 times and continue for 1 month or more, but the said dosage does not limit the scope of the present invention.
상기 약학적 조성물을 단위 용량 형태로 제형화하는 경우, 유효성분으로서 본 발명의 식물 추출물은 약 0.01 내지 1,500 ㎎의 단위 용량으로 함유되는 것이 바람직하고, 성인 치료에 필요한 투여량은 투여의 빈도와 강도에 따라 하루에 약 1 내지 500 ㎎ 범위가 보통이나 이에 한정되는 것은 아니며, 일부 환자의 경우 더 높은 1일 투여량이 바람직할 수도 있다.When the pharmaceutical composition is formulated in unit dosage form, the plant extract of the present invention as an active ingredient is preferably contained in a unit dose of about 0.01 to 1,500 mg, and the dosage required for treating an adult is the frequency and intensity of administration. As such, the range of about 1 to 500 mg per day is moderate but not limited, and a higher daily dosage may be desirable for some patients.
본 발명의 바람직한 구현예에 따르면, 본 발명의 조성물 내에 유효성분으로 함유되는 식물 추출물은 호중구 엘라스타아제의 활성을 억제하여 호중구 엘라스타아제에 의한 단백질 기질의 분해를 방지하는 효과가 있음을 확인할 수 있다(도 1a 내지 도 1c 참조).According to a preferred embodiment of the present invention, the plant extract contained as an active ingredient in the composition of the present invention can be confirmed that the effect of inhibiting the activity of neutrophil elastase to prevent degradation of the protein substrate by neutrophil elastase (See FIGS. 1A-1C).
또한, 본 발명은 상기 식물 추출물을 유효성분으로 함유하는 호중구 엘라스타아제의 활성과 연관된 질환 증상의 개선용 건강식품 조성물을 제공한다.In addition, the present invention provides a health food composition for improving disease symptoms associated with the activity of neutrophil elastase containing the plant extract as an active ingredient.
상기 식물 추출물은 상기 건강식품 조성물의 총 중량에 대하여 0.005 내지 20.0 중량%의 함량으로 함유되는 것이 바람직하고, 0.01 내지 10.0 중량%의 함량으로 함유되는 것이 보다 바람직하나 이에 한정되는 것은 아니다. 상기 식물 추출물의 유효 함량이 0.005 중량% 미만일 경우에는 호중구 엘라스타아제의 활성 억제 효과가 미약할 수 있고, 20 중량%를 초과할 경우에는 함유량 증가에 따른 뚜렷한 상승 효과가 떨어져 비경제적이다.The plant extract is preferably contained in an amount of 0.005 to 20.0% by weight based on the total weight of the health food composition, more preferably in an amount of 0.01 to 10.0% by weight, but is not limited thereto. If the effective amount of the plant extract is less than 0.005% by weight may be a weak effect of inhibiting the activity of neutrophil elastase, when it exceeds 20% by weight is not economically clear synergistic effect of the increase in content.
상기 건강식품 조성물은 본 발명에 따른 식물 추출물 외에 본 발명이 목적으로 하는 효과를 손상시키지 않는 범위 내에서, 바람직하게는 상기 식물 추출물에 상승효과를 줄 수 있는 다른 성분 등을 추가로 함유할 수 있다. 예를 들어 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 또는 담체를 포함할 수 있으나 이에 한정되는 것은 아니다.In addition to the plant extract according to the present invention, the health food composition may further contain other ingredients, such as synergistic effects, preferably within the range not impairing the effect of the present invention. . For example, but may include, but are not limited to, conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments and flavorings, or carriers.
또한, 본 발명의 건강식품 조성물은 식품 제조시 통상적으로 첨가되는 성분을 포함할 수 있고, 예컨대 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 추가로 포함할 수 있으나 이에 한정되는 것은 아니다. 상기 탄수화물의 예는 모노사카라이드, 예를 들면, 포도당, 과당 등; 디사카라이드, 예를 들면, 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들면, 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알코올을 들 수 있으나 이에 한정되는 것은 아니다. 상기 향미제로는 천연 향미제 타우마틴, 스테비아 추출물 및 합성 향미제를 사용할 수 있다. 예컨대, 본 발명의 건강식품 조성물이 드링크제로 제조되는 경우에는 본 발명의 식물 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 천연 추출액 등이 추가로 포함될 수 있다.In addition, the health food composition of the present invention may include ingredients that are commonly added in the manufacture of food, such as protein, carbohydrates, fats, nutrients, seasonings and flavorings may further include, but are not limited thereto. Examples of such carbohydrates are monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, erythritol, and the like. As the flavoring agent, natural flavoring agent taumartin, stevia extract and synthetic flavoring agent may be used. For example, when the health food composition of the present invention is prepared with a drink, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, natural extracts, and the like may be further included in addition to the plant extract of the present invention.
상기 건강식품 조성물의 종류에는 특별한 제한은 없다. 본 발명에 따른 식물 추출물을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함하는 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강 기능 식품을 모두 포함할 수 있다.There is no particular limitation on the kind of the health food composition. Examples of the food to which the plant extract according to the present invention may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, including various kinds of soups, beverages , Tea, drink, alcoholic beverages and vitamin complexes, and the like, may include all of the health functional foods in the conventional sense.
이하, 본 발명을 실시예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail by way of examples.
단, 하기 실시예는 본 발명을 예시하기 위한 것일 뿐, 본 발명의 내용이 하기 실시예에 의해 한정되는 것은 아니다.However, the following examples are only for illustrating the present invention, and the contents of the present invention are not limited by the following examples.
실시예 1. 식물 추출물의 제조Example 1 Preparation of Plant Extract
본 발명의 조성물의 유효성분으로 포함되는 딸기, 메밀, 쌀보리, 찰수수, 율무, 기장, 백미, 참마, 팥 및 권백 추출물과, 양성 대조군으로 사용되는 통밀, 메조, 금귤 과피, 로즈마리 및 얌 추출물을 각각 제조하였다. 이를 위하여, 상기 각각의 식물 원료에 6배의 증류수를 가해 85℃에서 12시간 추출하고 추출액을 여과하여 10℃로 냉각하였다. 잔사에 대해서는 6배의 증류수를 가해 12시간 추출을 3회 추가로 실시하여 추출액을 여과 후 모두 합하여 10℃로 냉각하였다. 냉각이 완료된 추출액을 4℃에서 15분 동안 6,000rpm으로 원심분리하여 침전물을 제거하여 각각의 식물 추출물을 제조하였다.Strawberries, buckwheat, rice barley, waxy water, yulmu, millet, white rice, yam, red beans, and white beans extracts included as an active ingredient of the composition of the present invention, and whole wheat, meso, kumquat rind, rosemary and yam extract used as positive controls, respectively. Prepared. To this end, 6 times distilled water was added to each of the plant raw materials, followed by extraction at 85 ° C. for 12 hours, and the extract was filtered and cooled to 10 ° C. For the residue, 6 times distilled water was added, extraction was further performed three times for 12 hours, and the extracts were combined after filtration and cooled to 10 ° C. The cooled extracts were centrifuged at 6,000 rpm for 15 minutes at 4 ° C. to remove precipitates, thereby preparing respective plant extracts.
실시예 2. 식물 추출물이 호중구 엘라스타아제의 활성에 미치는 영향Example 2 Effect of Plant Extracts on the Activity of Neutrophil Elastase
실시예 1에서 제조한 3 ㎎/㎖ 농도의 각종 식물 추출물들을 6 ㎎/㎖ 농도의 재조합 인간 호중구 엘라스타아제와 3 ㎍/㎖ 농도의 재조합 인간 바이글리칸 단백질과 혼합하여 100 mM Tris-HCl, pH 7.5, 500 mM NaCl 버퍼 내에서 24시간 동안 37℃에서 반응시켰으며, 상기 바이글리칸 단백질의 분해 여부를 확인하기 위하여 웨스턴 블롯 방법으로 각 샘플을 확인하였다. 웨스턴 블랏을 수행하기 상기 반응액의 1/3의 부피만큼 4× 라멜리 버퍼를 첨가하여 5분간 끓인 후, 10% SDS-PAGE 젤에 15 ㎕씩 로딩하여 20 mA/gel로 2시간 동안 전기영동하였고, 이를 니트로셀룰로오스 멤브레인에 35 V로 2시간 동안 냉장실에서 트랜스퍼하였다. 트랜스퍼가 완료된 멤브레인은 3% 탈지분유가 함유된 TBS-T 버퍼(Tween 20을 0.05% 함유하는 Tris계 식염수 버퍼)로 1시간 동안 상온에서 블로킹하였고, TBS-T 버퍼로 세척 후 바이글리칸 항체(AF2667, R&D systems)를 1:1,000으로 희석하여 냉장실에서 밤새 반응시켰다. 이를 다시 TBS-T 버퍼로 세척한 후 HRP 효소가 결합된 2차 항체를 1:10,000으로 희석하여 상온에서 1시간 동안 반응시켰고, 다시 TBS-T 버퍼로 세척한 후, 화학발광 용액을 통해 필름에 감광하여 바이글리칸 단백질의 양을 확인하였다.Various plant extracts prepared in Example 1 at 3 mg / ml were mixed with recombinant human neutrophil elastase at 6 mg / ml and recombinant human biglycan protein at 3 μg / ml, and then 100 mM Tris-HCl, The reaction was carried out at 37 ° C. for 24 hours in a pH 7.5, 500 mM NaCl buffer, and each sample was identified by a Western blot method in order to confirm the degradation of the Blycancan protein. Perform western blot, add 4 × lamelli buffer to the volume of 1/3 of the reaction solution and boil for 5 minutes, load 15 μl into 10% SDS-PAGE gel and electrophoresis at 20 mA / gel for 2 hours. This was transferred to a nitrocellulose membrane at 35 V for 2 hours in the refrigerator. Transfer completed membranes were blocked with TBS-T buffer containing 3% skim milk powder (Tris-based saline buffer containing 0.05% of Tween 20) for 1 hour at room temperature, washed with TBS-T buffer and then washed with BIG glycan antibody ( AF2667, R & D systems) was diluted 1: 1,000 and reacted overnight in the cold room. After washing this again with TBS-T buffer, the secondary antibody conjugated with HRP enzyme was diluted 1: 10,000 and reacted at room temperature for 1 hour. After washing with TBS-T buffer, the film was washed with chemiluminescent solution. Photosensitized to determine the amount of Beagle glycan protein.
그 결과, 호중구 엘라스타아제 없이 용매(Vehicle, V)와 바이글리칸 단백질만 처리된 샘플에서는 진하게 나타나는 바이글리칸이 호중구 엘라스타아제가 함께 첨가될 경우 대부분 분해되었지만, 실시예 1에서 제조한 각종 식물 추출물을 함께 처리한 경우에는 호중구 엘라스타아제에 의한 바이글리칸의 분해가 억제되어, 웨스턴 블롯 분석 상에서 분해되지 않고 남은 바이글리칸이 검출되었다(도 1a 내지 도 1c). 상기 결과로부터, 실시예 1에서 제조한 식물 추출물들이 각각 호중구 엘라스타아제의 활성을 억제하는 효과가 있음을 확인하였다.As a result, in the sample treated only with the solvent (Vehicle, V) and the diglycan protein without the neutrophil elastase, the dark diglycan was decomposed mostly when the neutrophil elastase was added together. When the plant extracts were treated together, the degradation of diglycans by neutrophil elastase was inhibited, and the remaining diglycans were detected in the western blot analysis (FIGS. 1A to 1C). From the above results, it was confirmed that the plant extracts prepared in Example 1 each had an effect of inhibiting the activity of neutrophil elastase.
제조예 1. 약학적 조성물의 제조Preparation Example 1 Preparation of Pharmaceutical Composition
<1-1> 산제의 제조<1-1> Preparation of Powder
실시예 1의 식물 추출물 2 g2 g of plant extract of Example 1
유당 1 g1 g lactose
상기의 성분을 혼합하고 기밀포에 충진하여 산제를 제조하였다.The above ingredients were mixed and filled in airtight cloth to prepare a powder.
<1-2> 정제의 제조<1-2> Preparation of Tablet
실시예 1의 식물 추출물 100 ㎎100 mg of plant extract of Example 1
옥수수전분 100 ㎎Corn starch 100 mg
유당 100 ㎎Lactose 100 mg
스테아린산 마그네슘 2 ㎎2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 정제의 제조 방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
<1-3> 캡슐제의 제조<1-3> Preparation of Capsule
실시예 1의 식물 추출물 100 ㎎100 mg of plant extract of Example 1
옥수수전분 100 ㎎Corn starch 100 mg
유당 100 ㎎Lactose 100 mg
스테아린산 마그네슘 2 ㎎2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.
<1-4> 환의 제조<1-4> Preparation of the ring
실시예 1의 식물 추출물 1 g1 g of plant extract of Example 1
유당 1.5 gLactose 1.5 g
글리세린 1 g1 g of glycerin
자일리톨 0.5 gXylitol 0.5 g
상기의 성분을 혼합한 후, 통상의 방법에 따라 1환 당 4g이 되도록 제조하였다.After mixing the above components, it was prepared to be 4g per ring according to a conventional method.
<1-5> 과립의 제조<1-5> Preparation of Granules
실시예 1의 식물 추출물 150 ㎎150 mg of plant extract of Example 1
대두추출물 50 ㎎Soy extract 50 mg
포도당 200 ㎎Glucose 200 mg
전분 600 ㎎Starch 600 mg
상기의 성분을 혼합한 후, 30% 에탄올 100 ㎎을 첨가하여 섭씨 60℃에서 건조하여 과립을 형성한 후 포에 충진하였다.After mixing the above components, 100 mg of 30% ethanol was added and dried at 60 ° C. to form granules, which were then filled into fabrics.
제조예 2. 건강식품 조성물의 제조Preparation Example 2 Preparation of Health Food Composition
<2-1> 밀가루 식품의 제조<2-1> Preparation of Flour Food
실시예 1의 식물 추출물 0.5 ∼~5.0 중량부를 밀가루에 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하였다.0.5-5.0 parts by weight of the plant extract of Example 1 was added to the flour, and bread, cake, cookies, crackers and noodles were prepared using this mixture.
<2-2> 스프 및 육즙(gravies)의 제조<2-2> Preparation of Soups and Gravys
실시예 1의 식물 추출물 0.1 ∼ 5.0 중량부를 스프 및 육즙에 첨가하여 건강 증진용 육가공 제품, 면류의 수프 및 육즙을 제조하였다.0.1 to 5.0 parts by weight of the plant extract of Example 1 was added to the soup and gravy to prepare a health-producing meat product, soup of noodles and gravy.
<2-3> 그라운드 비프(ground beef)의 제조<2-3> Preparation of Ground Beef
실시예 1의 식물 추출물 10 중량부를 그라운드 비프에 첨가하여 건강 증진용 그라운드 비프를 제조하였다.10 parts by weight of the plant extract of Example 1 was added to the ground beef to prepare a ground beef for health promotion.
<2-4> 유제품의 제조<2-4> Production of Dairy Products
실시예 1의 식물 추출물 5∼10 중량부를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.5 to 10 parts by weight of the plant extract of Example 1 was added to milk, and the milk was used to prepare various dairy products such as butter and ice cream.
<2-5> 선식의 제조<2-5> Preparation of Wire
현미, 보리, 찹쌀, 율무를 공지의 방법으로 알파화시켜 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다. 검정콩, 검정깨, 들깨도 공지의 방법으로 쪄서 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다. 실시예 1의 식물 추출물을 진공 농축기에서 감압농축하고, 분무, 열풍건조기로 건조하여 얻은 건조물을 분쇄기로 입도 60 메쉬로 분쇄하여 건조 분말을 얻었다. 상기에서 제조한 곡물류, 종실류 및 실시예 1의 식물 추출물의 건조 분말을 다음의 비율로 배합하여 제조하였다.Brown rice, barley, glutinous rice, and yulmu were alphad by a known method, and then dried and roasted to prepare a powder having a particle size of 60 mesh. Black beans, black sesame seeds, and perilla were also steamed and dried in a known manner, and then roasted to prepare a powder having a particle size of 60 mesh. The plant extract of Example 1 was concentrated under reduced pressure in a vacuum concentrator, and the dried product obtained by drying with a spray and a hot air dryer was pulverized with a particle size of 60 mesh using a grinder to obtain a dry powder. The dry powders of the grains, seeds and plant extracts of Example 1 prepared above were formulated in the following proportions.
곡물류(현미 30 중량부, 율무 15 중량부, 보리 20 중량부), 종실류(들깨 7 중량부, 검정콩 8 중량부, 검정깨 7 중량부), 실시예 1의 식물 추출물의 건조 분말(3 중량부), 영지(0.5 중량부), 지황(0.5 중량부)Cereals (30 parts by weight brown rice, 15 parts by weight of barley, 20 parts by weight of barley), seeds (7 parts by weight perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds), dry powder (3 parts by weight) of the plant extract of Example 1 (Part), Ganoderma lucidum (0.5 parts by weight), Sulfur (0.5 parts by weight)
제조예 3. 음료의 제조Preparation Example 3 Preparation of Beverage
<3-1> 건강음료의 제조<3-1> Preparation of health drink
액상과당(0.5%), 올리고당(2%), 설탕(2%), 식염(0.5%), 물(75%)과 같은 부재료와 실시예 1의 식물 추출물 5 g을 균질하게 배합하여 순간 살균을 한 후 이를 유리병, 패트병 등 소포장 용기에 포장하여 제조하였다.Instant sterilization by homogeneously combining 5 g of the plant extract of Example 1 with subsidiary materials such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%) and water (75%). Then it was prepared by packaging in a small packaging container such as glass bottles, plastic bottles.
<3-2> 야채 주스의 제조<3-2> Preparation of Vegetable Juice
실시예 1의 식물 추출물 5 g을 토마토 또는 당근 주스 1,000 ㎖에 가하여 야채 주스를 제조하였다.Vegetable juice was prepared by adding 5 g of the plant extract of Example 1 to 1,000 ml of tomato or carrot juice.
<3-3> 과일 주스의 제조<3-3> Preparation of Fruit Juice
실시예 1의 식물 추출물 1 g을 사과 또는 포도 주스 1,000 ㎖에 가하여 과일 주스를 제조하였다.1 g of the plant extract of Example 1 was added to 1,000 ml of apple or grape juice to prepare a fruit juice.
Claims (10)
상기 호중구 엘라스타아제의 활성과 연관된 질환은 호중구 엘라스타아제의 과도한 활성으로 인해 발생하는 질환인 약학적 조성물.The method according to claim 1,
The disease associated with the activity of neutrophil elastase is a disease caused by excessive activity of neutrophil elastase.
상기 호중구 엘라스타아제의 활성과 연관된 질환은 성인 호흡 곤란 증후군(ARDS), 낭성 섬유증, 폐 기종, 만성 기관지염, 기관지확장증, 만성 폐쇄성 폐 질환(COPD), 폐 고혈압증, 천식, 비염, 건선, 허혈-재관류 손상, 류마티스성 관절염, 골관절염, 전신성 염증성 반응 증후군(SIRS), 만성 창상, 암, 아테롬성 동맥경화증, 소화성 궤양, 크론병 및 궤양성 대장염으로 이루어진 군으로부터 선택되는 약학적 조성물.The method according to claim 2,
Diseases associated with the activity of neutrophil elastase include adult respiratory distress syndrome (ARDS), cystic fibrosis, pulmonary emphysema, chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD), pulmonary hypertension, asthma, rhinitis, psoriasis, ischemia- A pharmaceutical composition selected from the group consisting of reperfusion injury, rheumatoid arthritis, osteoarthritis, systemic inflammatory response syndrome (SIRS), chronic wounds, cancer, atherosclerosis, peptic ulcer, Crohn's disease and ulcerative colitis.
상기 식물 추출물은 딸기 추출물, 메밀 추출물, 쌀보리 추출물, 찰수수 추출물, 율무 추출물, 기장 추출물, 백미 추출물, 참마 추출물, 팥 추출물 및 권백 추출물로 이루어진 군으로부터 선택되는 1종 이상의 식물 추출물인 약학적 조성물.The method according to claim 1,
The plant extract is one or more plant extracts selected from the group consisting of strawberry extract, buckwheat extract, rice barley extract, waxy water extract, yulmu extract, millet extract, white rice extract, yam extract, red bean extract, and baekbaek extract.
상기 식물 추출물의 제조에 사용되는 추출용매는 물, 유기용매 또는 이들의 혼합물인 약학적 조성물.The method according to claim 1,
Extraction solvent used in the preparation of the plant extract is water, an organic solvent or a mixture thereof.
상기 유기용매는 알코올, 헥산, 에테르, 글리세롤, 프로필렌글리콜, 부틸렌글리콜, 에틸아세테이트, 메틸아세테이트, 디클로로메탄, 클로로포름, 벤젠 및 이들의 혼합용매로 이루어진 군으로부터 선택되는 약학적 조성물.The method according to claim 5,
The organic solvent is a pharmaceutical composition selected from the group consisting of alcohol, hexane, ether, glycerol, propylene glycol, butylene glycol, ethyl acetate, methyl acetate, dichloromethane, chloroform, benzene and mixed solvents thereof.
상기 호중구 엘라스타아제의 활성과 연관된 질환은 성인 호흡 곤란 증후군(ARDS), 낭성 섬유증, 폐 기종, 만성 기관지염, 기관지확장증, 만성 폐쇄성 폐 질환(COPD), 폐 고혈압증, 천식, 비염, 건선, 허혈-재관류 손상, 류마티스성 관절염, 골관절염, 전신성 염증성 반응 증후군(SIRS), 만성 창상, 암, 아테롬성 동맥경화증, 소화성 궤양, 크론병 및 궤양성 대장염으로 이루어진 군으로부터 선택되는 건강식품 조성물.The method according to claim 7,
Diseases associated with the activity of neutrophil elastase include adult respiratory distress syndrome (ARDS), cystic fibrosis, pulmonary emphysema, chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD), pulmonary hypertension, asthma, rhinitis, psoriasis, ischemia- A health food composition selected from the group consisting of reperfusion injury, rheumatoid arthritis, osteoarthritis, systemic inflammatory response syndrome (SIRS), chronic wounds, cancer, atherosclerosis, peptic ulcer, Crohn's disease and ulcerative colitis.
상기 식물 추출물은 딸기 추출물, 메밀 추출물, 쌀보리 추출물, 찰수수 추출물, 율무 추출물, 기장 추출물, 백미 추출물, 참마 추출물, 팥 추출물 및 권백 추출물로 이루어진 군으로부터 선택되는 1종 이상의 식물 추출물인 건강식품 조성물.The method according to claim 7,
The plant extract is a health food composition is one or more plant extracts selected from the group consisting of strawberry extract, buckwheat extract, rice barley extract, waxy water extract, yulmu extract, millet extract, white rice extract, yam extract, red bean extract and baekbaek extract.
상기 식물 추출물의 제조에 사용되는 추출용매는 물, 유기용매 또는 이들의 혼합물인 건강식품 조성물.The method according to claim 7,
Extraction solvent used in the preparation of the plant extract is a health food composition is water, an organic solvent or a mixture thereof.
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