KR102252126B1 - Composition for prevention or treatment respiratory diseases comprising combination extracts of Chrysanthemum morifolium Ramatuelle and Scutellaria baicalensis as an active ingredient - Google Patents
Composition for prevention or treatment respiratory diseases comprising combination extracts of Chrysanthemum morifolium Ramatuelle and Scutellaria baicalensis as an active ingredient Download PDFInfo
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- KR102252126B1 KR102252126B1 KR1020180093338A KR20180093338A KR102252126B1 KR 102252126 B1 KR102252126 B1 KR 102252126B1 KR 1020180093338 A KR1020180093338 A KR 1020180093338A KR 20180093338 A KR20180093338 A KR 20180093338A KR 102252126 B1 KR102252126 B1 KR 102252126B1
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- extract
- chrysanthemum
- golden
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- respiratory diseases
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Abstract
본 발명은 국화(Chrysanthemum morifolium Ramatuelle) 및 황금(Scutellaria baicalensis) 혼합 추출물을 유효성분으로 함유하는 호흡기 질환 예방 또는 치료용 약학적 조성물에 관한 것으로, 구체적으로 최적 혼합 비율로 혼합된 국화 및 황금 혼합 추출물이 세포독성이 없고, 유의적인 항염증 효과를 나타내며, 기관지 세포에서 염증성 점액단백질의 분비를 유의적으로 억제하고, 천식 및 미세먼지에 의한 호흡기 질환 개선 효과가 있으므로, 기관지염, 천식, 폐렴, 만성 폐쇄성 폐질환 등을 포함하는 호흡기 질환 예방 또는 치료용, 진해 또는 거담용 조성물의 유효성분으로 이용할 수 있다.The present invention is Chrysanthemum morifolium Ramatuelle ) and golden ( Scutellaria baicalensis ) It relates to a pharmaceutical composition for the prevention or treatment of respiratory diseases containing a mixed extract as an active ingredient, specifically, the mixed extract of chrysanthemum and gold mixed at the optimal mixing ratio has no cytotoxicity, significant Respiratory diseases including bronchitis, asthma, pneumonia, chronic obstructive pulmonary disease, etc., as it exhibits anti-inflammatory effect, significantly inhibits the secretion of inflammatory mucous proteins from bronchial cells, and has the effect of improving respiratory diseases due to asthma and fine dust. It can be used as an active ingredient of a composition for prevention or treatment, antitussive or expectorant.
Description
본 발명은 국화(Chrysanthemum morifolium Ramatuelle) 추출물 및 황금(Scutellaria baicalensis) 추출물을 유효성분으로 함유하고, 이들을 최적 혼합 비율로 함유하는, 호흡기 질환 예방 또는 치료용, 또는 진해 및 거담용 조성물에 관한 것이다.
The present invention is Chrysanthemum morifolium Ramatuelle ) extract and golden ( Scutellaria) baicalensis ) containing the extract as an active ingredient, and containing them in an optimal mixing ratio, for preventing or treating respiratory diseases, or to a composition for antitussive and expectorant.
우리 몸의 호흡기는 물리 화학적인 자극에 대해 끊임없이 방어하고 있는 기관 중 하나로 자극물질이 호흡기로 유입되면 대부분의 자극물질은 코털에 걸려 호흡기로 들어오지 못하나 이를 통과한 미세한 자극물질은 점액으로 둘러싸이고, 기도 벽에 위치한 미세한 섬모의 운동에 의해 위로 또는 밖으로 내보내 지게 되는데, 바로 이것이 기침의 기본 작용원리이다.
The respiratory system of our body is one of the organs that constantly defends against physicochemical stimulation. When an irritant enters the respiratory tract, most of the irritants get caught in the nose hair and cannot enter the respiratory tract, but the fine irritants that pass through it are surrounded by mucus and It is sent upward or out by the movement of the fine cilia located on the wall, which is the basic working principle of coughing.
상기한 바와 같이, 기침은 기도 점막 자극에 의해 반사적으로 일어나는 방어기전으로, 지나친 자극에 의한 지속적인 기침이 유발될 경우, 환자의 삶의 질을 경감시키고 악화시키게 된다. 또한, 기침과 같은 원리로 외부에서 먼지나 자극물질 등이 유입되면 우리 몸의 기관지에서는 타액과 함께 근육운동을 해서 외부로 밀어내게 되는데, 이것이 객담(가래) 형성의 원인이며 폐 등 기관지의 염증에 의해서 짙은 화농성 객담이 생기게 된다.
As described above, cough is a defense mechanism that occurs reflexively by irritation of the airway mucosa, and when persistent cough is induced by excessive irritation, the quality of life of the patient is reduced and worsened. In addition, when dust or irritants are introduced from the outside on the same principle as coughing, the bronchi of our body performs muscle movements with saliva and pushes them out. This is the cause of the formation of sputum (sputum) and inflammation of the bronchi such as lungs. By this, thick purulent sputum is produced.
결과적으로 찬 공기, 병원성 미생물을 포함한 외부 이물질, 대기 오염 물질, 알레르기 유발 물질 등과 같은 물리 화학적 요인 등에 의해 기침 및 가래가 발생되며 이를 크게 세 가지로 나눌 수 있다.
As a result, cough and sputum are caused by physical and chemical factors such as cold air, foreign substances including pathogenic microorganisms, air pollutants, and allergens, which can be largely divided into three categories.
첫째, 물리 화학적 요인으로 인해 후두, 기관, 기관지, 인두, 부비동, 횡격막 등의 기침 수용체를 자극하면 뇌의 연수 부위의 기침 중추에 자극이 전달되고 기침 반사가 일어난다. 이러한 자극성 기침 반사와 밀접히 관련 있는 진해제의 기전은, 중추성과 말초성으로 대별되며, 중추성 진해제의 기전은 연수의 해소 중추를 억제하여 기침을 조절하는 약물로서 코데인(codeine), 덱스트로메토르판(dextromethorphan), 노스캡핀(noscapine), 에페드린(ephedrine), 지페프롤(zipeprol) 등이 있는데 이러한 성분들은 종종 심혈관계 혈전반응이나 심근경색, 호흡억제, 진정작용, 위장장애 등의 부작용을 유발하는 경우가 있다. 말초성 진해제는 말초에 있는 신장 수용체(stretch receptor)에 작용하여 기침을 조절하는 것으로 상대적으로 중추성 진해제의 단점을 보완하여 안전하다는 장점이 있어, 최근에 이러한 진해제의 개발이 많이 시도되고 있다. 대표적인 약물로는 레보프로피진(levopropizine), 벤조나테이트(benzonatate), 벤조자인(benzozaine), 벤질알콜(benzyl alcohol) 등이 사용되고 있다.
First, when stimulating cough receptors such as the larynx, trachea, bronchi, pharynx, sinuses, and diaphragm due to physicochemical factors, the stimulation is transmitted to the cough center of the brain and the cough reflex occurs. The mechanisms of antitussive drugs, which are closely related to the stimulating cough reflex, are broadly classified into centrality and peripherality, and the mechanisms of central antitussive drugs are drugs that control cough by suppressing the remission center of soft water, codeine and dextromethorphan ( dextromethorphan), noscapine, ephedrine, and zipeprol.These ingredients often cause side effects such as cardiovascular thrombosis, myocardial infarction, respiratory depression, sedation, and gastrointestinal disorders. There is. Peripheral antitussive drugs act on the peripheral stretch receptor to control cough, and have the advantage of being safe by compensating for the shortcomings of the central antitussive drugs. Recently, many attempts have been made to develop such antitussive drugs. Representative drugs include levopropizine, benzonatate, benzozaine, and benzyl alcohol.
둘째, 물리 화학적 요인으로 인해 부교감 신경계가 활성화되면 기관지 평활근이 수축하고 따라서 기관지 경련이나 기관지 수축과 같은 증상이 나타날 수 있다. 이때, 베타 2 아고니스트(β2-adrenergic receptor agonist)는 베타 2 수용체를 자극하여 평활근을 이완시키고, 잔틴(xanthine) 유도체는 포스포디에스테라제(phosphodiesterase)의 억제에 의한 cAMP를 증가시키거나 기관지 평활근을 직접 이완시키는 역할을 하여 점액분비를 증대시키면서 점액을 용해시키며 섬모운동을 촉진시켜 진해, 거담 활성을 나타낸다. 이러한 작용을 나타내는 약물로는, 베타 2 아고니스트인 클렌부테롤(clenbuterol), 밤부테롤(bambuterol), 포르모테롤(formoterol) 등이 있고, 잔틴(xanthine) 유도체인, 테오필린(theophylline), 아미노필린(aminophylline), 아세피필린(acepifylline), 바미필린(bamifylline) 등이 있다.
Second, when the parasympathetic nervous system is activated due to physicochemical factors, bronchial smooth muscle contracts, and thus symptoms such as bronchospasm or bronchial contraction may appear. At this time, the
이외에 생성된 점액을 용해시켜 점도를 감소시키고 기관지의 섬모 운동을 촉진함으로써 객담 배출을 촉진시키는 점액 용해제 또는 거담제 등이 있다. 기도 점액은 기도에서 여러 가지 중요한 기능을 가진다. 즉, 외부에서 기도로 들어온 입자로부터 기도를 보호하고, 흡입공기의 습도를 유지하며, 흡입된 화학물질이나 가스 등을 점액의 단백질과 결합, 섬모 작용으로 제거하는 역할을 가진다. 또한, 점액은 이뮤노글로블린 A(IgA), 라이소자임(lysozyme), 락토페린(lactoferrin) 등과 같은 면역 기능에 중요한 역할을 하는 물질을 가지고 있다. 대부분의 거담제는 식물 등을 이용하여 수천 년 동안 민간약 또는 경험처방으로 사용하여 왔고 화합물로는 카르보시스테인(carbocysteine), N-아세틸시스테인(N-acetylcysteine), 시스테인 에틸에스테르 염산염 등과 같은 시스테인 유도체가 거담제로 사용되고 있다. 전술한 시스테인 유도체들이 거담제로 사용될 때 완전히 만족할 만한 것은 아니며 특히, N-아세틸 시스테인 및 시스테인 에틸에스테르 염산염은 모두 독성이 강하고 화학적으로 불안정한 문제점을 갖고 있다. 그러므로 물리, 화학적 안정성은 좋으면서 보다 적은 부작용과 독성, 우수한 거담효과를 갖는 거담제의 개발이 요구되어 왔다.
In addition, there are mucolytic agents or expectorant agents that reduce the viscosity by dissolving the generated mucus and promote ciliary movement of the bronchi, thereby promoting sputum discharge. Airway mucus has several important functions in the airways. In other words, it protects the airways from particles entering the airways from the outside, maintains the humidity of the inhaled air, and removes the inhaled chemical substances or gases through the binding of mucus proteins and cilia. In addition, mucus contains substances that play an important role in immune function, such as immunoglobulin A (IgA), lysozyme, and lactoferrin. Most expectorant agents have been used as folk medicines or empirical prescriptions for thousands of years using plants, etc., and as compounds, cysteine derivatives such as carbocysteine, N-acetylcysteine, and cysteine ethyl ester hydrochloride are used as expectorant agents. It is being used as. When the above-described cysteine derivatives are used as expectorants, they are not completely satisfactory, and in particular, N-acetyl cysteine and cysteine ethyl ester hydrochloride are both highly toxic and chemically unstable. Therefore, development of an expectorant agent having good physical and chemical stability, less side effects, toxicity, and excellent expectorant effect has been required.
셋째, 물리 화학적 요인으로 인해 비만세포에서 염증매개물질 등이 방출하게 된다. 비만세포는 히스타민(histamine)이나 사이토카인(cytokine) 등과 같은 염증 매개물질을 함유하는 작은 사이토플라스믹 그라뉼(cytoplasmic granule)을 포함하고 있다. 알러지 유발인자(Allergen)에 노출되면 체내에서는 IgE라는 항체가 B 세포에서 생성되는데, 이것이 비만세포 표면에 부착된다. 이후 다시 알러지 유발인자에 노출되면 IgE가 부착된 비만세포에서는 강력한 염증 매개체인 히스타민을 비롯한 화학물질들이 방출되어 이에 의해 기도 내 분비물, 염증에 의한 삼출액, 흡입 이물, 세균 등이 증가하게 되며 이는 객담 형성으로 이어진다. 진해제로 널리 쓰이는 코데인 등의 기존 약물들은 호흡 및 기침에 대한 진정 작용이 뛰어나지만 비만세포의 탈과립을 유발하여 히스타민을 유리시키는 부작용을 가지고 있다.
Third, inflammatory mediators are released from mast cells due to physicochemical factors. Mast cells contain small cytoplasmic granules containing inflammatory mediators such as histamine and cytokines. When exposed to an allergen, an antibody called IgE is produced in B cells in the body, which attaches to the surface of mast cells. Afterwards, when exposed to allergens again, chemical substances including histamine, a strong inflammatory mediator, are released from mast cells with IgE attached, thereby increasing secretions in the airways, effusion due to inflammation, inhalation foreign matter, bacteria, etc., which results in the formation of sputum. Leads to Existing drugs, such as codeine, which are widely used as antitussives, have excellent sedative action against breathing and cough, but have side effects of releasing histamine by causing degranulation of mast cells.
상기한 바와 같이, 기존의 진해 거담제는 부작용과 독성 및 약물 자체의 화학적 불안정성 등으로 인한 문제점을 가지고 있다. 이러한 문제를 해결하기 위하여, 최근에는 천연물 유래의 진해거담제 연구가 활발히 진행되고 있으며, 이와 관련한 대표적인 연구로는 기도의 미주신경을 자극하여 점막의 분비를 촉진시켜 거담작용을 발현함과 동시에 진해작용의 보조적 역할을 하는 사포닌(saponin), 알칼로이드(alkaloid) 등을 함유하는 식물 (김숙영 외, Kor. J. Pharmacogn.19(2):133-140, 1998)에 관한 보고가 있기도 하지만, 그 성과는 아직 미미한 실정이다.
As described above, existing antitussive expectorants have problems due to side effects, toxicity, and chemical instability of the drug itself. In order to solve this problem, researches on antitussive expectorant drugs derived from natural substances have been actively conducted in recent years, and a representative study related to this is to stimulate the vagus nerve of the airways to promote the secretion of the mucous membrane, thereby expressing the expectorant function and at the same time There are reports of plants containing saponins, alkaloids, etc., which play an auxiliary role (Sook-young Kim et al., Kor. J. Pharmacogn. 19(2):133-140, 1998), but the results have not yet been achieved. This is insignificant.
이에, 본 발명자들은 천연물 유래 호흡기 질환 치료제를 개발하기 위해 노력한 결과, 최적 혼합 비율로 혼합된 국화(Chrysanthemum morifolium Ramatuelle) 및 황금(Scutellaria baicalensis) 혼합 추출물이 세포독성이 없고, 유의적인 항염증 효과를 나타내며, 기관지 세포에서 염증성 점액단백질의 분비를 유의적으로 억제하고, 천식 및 미세먼지에 의한 호흡기 질환 개선 효과가 있음을 확인하여, 호흡기 질환 예방 또는 치료용, 진해 또는 거담용 조성물의 유효성분으로 이용할 수 있음을 밝힘으로써, 본 발명을 완성하였다.
Accordingly, the present inventors have endeavored to develop a therapeutic agent for respiratory diseases derived from natural products, as a result of which chrysanthemum is mixed in an optimal mixing ratio ( Chrysanthemum morifolium Ramatuelle ) and golden ( Scutellaria) baicalensis ) mixed extract has no cytotoxicity, shows significant anti-inflammatory effect, significantly inhibits the secretion of inflammatory mucous proteins from bronchial cells, and has the effect of improving respiratory diseases due to asthma and fine dust. By revealing that it can be used as an active ingredient of a composition for preventing or treating diseases, antitussive or expectorant, the present invention was completed.
본 발명의 목적은 국화(Chrysanthemum morifolium Ramatuelle) 추출물 및 황금(Scutellaria baicalensis) 추출물을 유효성분으로 함유하고, 상기 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하는, 호흡기 질환 예방 또는 치료용 조성물을 제공하기 위한 것이다.
An object of the present invention is Chrysanthemum morifolium Ramatuelle ) extract and golden ( Scutellaria) baicalensis ) containing the extract as an active ingredient, and the chrysanthemum extract: golden extract in a weight ratio of 5: 5 to 8: 2, to provide a composition for preventing or treating respiratory diseases.
상기 목적을 달성하기 위하여, 본 발명은 국화(Chrysanthemum morifolium Ramatuelle) 추출물 및 황금(Scutellaria baicalensis) 추출물을 유효성분으로 함유하고, 상기 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하는, 호흡기 질환 예방 또는 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention is chrysanthemum ( Chrysanthemum morifolium Ramatuelle ) extract and gold ( Scutellaria baicalensis ) contains the extract as an active ingredient, and the chrysanthemum extract: golden extract in a weight ratio of 5: 5 to 8: 2 provides a pharmaceutical composition for preventing or treating respiratory diseases.
또한, 본 발명은 국화 추출물 및 황금 추출물을 유효성분으로 함유하고, 상기 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하는, 진해 또는 거담용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for Jinhae or Geodam containing chrysanthemum extract and golden extract as active ingredients, and containing the chrysanthemum extract: golden extract in a weight ratio of 5:5 to 8:2.
또한, 본 발명은 국화 추출물 및 황금 추출물을 유효성분으로 함유하고, 상기 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하는, 호흡기 질환 예방 또는 개선용 건강식품을 제공한다.In addition, the present invention provides a health food for preventing or improving respiratory diseases, containing chrysanthemum extract and golden extract as active ingredients, and containing the chrysanthemum extract: golden extract in a weight ratio of 5:5 to 8:2.
아울러, 본 발명은 국화 추출물 및 황금 추출물을 유효성분으로 함유하고, 상기 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하는, 진해 또는 거담용 건강식품을 제공한다.
In addition, the present invention provides a health food for Jinhae or Geodam containing chrysanthemum extract and golden extract as active ingredients, and containing the chrysanthemum extract: golden extract in a weight ratio of 5:5 to 8:2.
본 발명의 최적 혼합 비율로 혼합된 국화 및 황금 혼합 추출물이 세포독성이 없고, 유의적인 항염증 효과를 나타내며, 기관지 세포에서 염증성 점액단백질의 분비를 유의적으로 억제하고, 천식 및 미세먼지에 의한 호흡기 질환 개선 효과가 있으므로, 기관지염, 천식, 폐렴, 만성 폐쇄성 폐질환 등을 포함하는 호흡기 질환 예방 또는 치료용 조성물의 유효성분으로 유용하게 이용할 수 있다.
Chrysanthemum and golden mixed extracts mixed at the optimal mixing ratio of the present invention have no cytotoxicity, show significant anti-inflammatory effect, significantly inhibit the secretion of inflammatory mucoproteins from bronchial cells, and respiratory tract due to asthma and fine dust Since it has a disease improvement effect, it can be usefully used as an active ingredient of a composition for preventing or treating respiratory diseases including bronchitis, asthma, pneumonia, and chronic obstructive pulmonary disease.
도 1은 RAW 264.7 세포에 LPS(Lipopolysaccharide) 1 ㎍/㎖, 또는 LPS 1 ㎍/㎖와 본 발명의 실시예에서 제조한 국화(Chrysanthemum morifolium Ramatuelle) 추출물, 황금(Scutellaria baicalensis) 추출물 또는 국화 및 황금 혼합 추출물을 처리한 후 세포생존율을 확인한 도로서,
도 1A에서는 RAW 264.7 세포에 LPS 1 ㎍/㎖, LPS 1 ㎍/㎖ 및 국화 열수 추출물(1) 200 ㎍/㎖, 또는 LPS 1 ㎍/㎖ 및 황금 열수 추출물(2) 200 ㎍/㎖를 처리한 후 세포생존율을 확인한 도이고,
도 1B에서는 RAW 264.7 세포에 LPS 1 ㎍/㎖, LPS 1 ㎍/㎖ 및 국화 에탄올 추출물(3) 200 ㎍/㎖, 또는 LPS 1 ㎍/㎖ 및 황금 에탄올 추출물(4) 200 ㎍/㎖를 처리한 후 세포생존율을 확인한 도이며,
도 1C는 RAW 264.7 세포에 LPS 1 ㎍/㎖, LPS 1 ㎍/㎖ 및 황금 열수 추출물, LPS 1 ㎍/㎖ 및 국화 에탄올 추출물, 또는 LPS 1 ㎍/㎖ 및 다양한 혼합 비율로 혼합한 국화 및 황금 혼합 추출물을 농도별로 처리한 후 세포생존율을 확인한 도이다.
도 2는 RAW 264.7 세포에 LPS 1 ㎍/㎖, 또는 LPS 1 ㎍/㎖와 본 발명의 실시예에서 제조한 국화 추출물, 황금 추출물 또는 국화 및 황금 혼합 추출물을 처리한 후 NO 생성 정도를 확인한 도로서,
도 2A에서는 RAW 264.7 세포에 LPS 1 ㎍/㎖, LPS 1 ㎍/㎖ 및 국화 열수 추출물(1) 200 ㎍/㎖, 또는 LPS 1 ㎍/㎖ 및 황금 열수 추출물(2) 200 ㎍/㎖를 처리한 후 NO 생성 정도를 확인한 도이고,
도 2B에서는 RAW 264.7 세포에 LPS 1 ㎍/㎖, LPS 1 ㎍/㎖ 및 국화 에탄올 추출물(3) 200 ㎍/㎖, 또는 LPS 1 ㎍/㎖ 및 황금 에탄올 추출물(4) 200 ㎍/㎖를 처리한 후 NO 생성 정도를 확인한 도이며,
도 2C는 RAW 264.7 세포에 LPS 1 ㎍/㎖, LPS 1 ㎍/㎖ 및 황금 열수 추출물, LPS 1 ㎍/㎖ 및 국화 에탄올 추출물, 또는 LPS 1 ㎍/㎖ 및 다양한 혼합 비율로 혼합한 국화 및 황금 혼합 추출물을 농도별로 처리한 후 NO 생성 정도를 확인한 도이다.
도 3은 NCI-H292 세포에 LPS 20 ㎍/㎖ 및 PMA 100 ng/㎖, LPS 20 ㎍/㎖, PMA 100 ng/㎖ 및 황금 열수 추출물, LPS 20 ㎍/㎖, PMA 100 ng/㎖ 및 국화 에탄올 추출물, 또는 LPS 20 ㎍/㎖, PMA 100 ng/㎖ 및 다양한 혼합 비율로 혼합한 국화 및 황금 혼합 추출물을 농도별로 처리한 후 세포생존율을 확인한 도이다.
도 4는 NCI-H292 세포에 LPS 20 ㎍/㎖ 및 PMA 100 ng/㎖, LPS 20 ㎍/㎖, PMA 100 ng/㎖ 및 황금 열수 추출물, LPS 20 ㎍/㎖, PMA 100 ng/㎖ 및 국화 에탄올 추출물, 또는 LPS 20 ㎍/㎖, PMA 100 ng/㎖ 및 다양한 혼합 비율로 혼합한 국화 및 황금 혼합 추출물을 농도별로 처리한 후 MUC5AC의 분비량을 확인한 도이다.
도 5는 A549 세포에 PMA 20 또는 100 ng/㎖, PMA 20 ng/㎖ 및 황금 열수 추출물 100 ㎍/㎖, PMA 20 ng/㎖ 및 국화 에탄올 추출물 1000 ㎍/㎖, 또는 PMA 20 ng/㎖ 및 다양한 혼합 비율로 혼합한 국화 및 황금 혼합 추출물 1000 ㎍/㎖를 처리한 후 PGE2의 분비량을 확인한 도이다.FIG. 1 shows, in RAW 264.7 cells, 1 µg/ml of LPS (Lipopolysaccharide), or 1 µg/ml of LPS and chrysanthemums prepared in an example of the present invention ( Chrysanthemum morifolium). Ramatuelle ) extract, golden ( Scutellaria) baicalensis ) as a diagram confirming the cell viability after treating the extract or the mixed extract of chrysanthemum and gold,
In Fig. 1A, RAW 264.7 cells were treated with 1 µg/ml of LPS, 1 µg/ml of LPS and 200 µg/ml of chrysanthemum hot water extract (1), or 1 µg/ml of LPS and 200 µg/ml of golden hot water extract (2). It is the degree of confirming the cell viability after,
In Fig. 1B, RAW 264.7 cells were treated with 1 µg/ml of LPS, 1 µg/ml of LPS and 200 µg/ml of chrysanthemum ethanol extract (3), or 1 µg/ml of LPS and 200 µg/ml of golden ethanol extract (4). It is the degree of confirming the cell viability after,
Figure 1C is a mixture of chrysanthemum and gold mixed with
FIG. 2 is a diagram illustrating the degree of NO production after treatment with
In FIG. 2A, RAW 264.7 cells were treated with 1 µg/ml of LPS, 1 µg/ml of LPS and 200 µg/ml of chrysanthemum hot water extract (1), or 1 µg/ml of LPS and 200 µg/ml of golden hot water extract (2). It is a degree that confirms the degree of NO generation after,
In Fig. 2B, RAW 264.7 cells were treated with 1 µg/ml of LPS, 1 µg/ml of LPS and 200 µg/ml of chrysanthemum ethanol extract (3), or 1 µg/ml of LPS and 200 µg/ml of golden ethanol extract (4). It is a degree that confirms the degree of NO generation after
Fig. 2C is a mixture of chrysanthemum and gold mixed with
Figure 3 shows the NCI-
Figure 4 shows
Figure 5 shows
이하, 본 발명을 보다 상세히 설명한다.
Hereinafter, the present invention will be described in more detail.
본 발명은 국화(Chrysanthemum morifolium Ramatuelle) 추출물 및 황금(Scutellaria baicalensis) 추출물을 유효성분으로 함유하고, 상기 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하는, 호흡기 질환 예방 또는 치료용 약학적 조성물을 제공한다.The present invention is Chrysanthemum morifolium Ramatuelle ) extract and golden ( Scutellaria) baicalensis ) contains the extract as an active ingredient, and the chrysanthemum extract: golden extract in a weight ratio of 5: 5 to 8: 2 provides a pharmaceutical composition for preventing or treating respiratory diseases.
본 발명의 유효성분인 국화 추출물 및 황금 추출물 각각은 하기의 단계들을 포함하는 방법에 의해 제조되는 것이 바람직하나, 이에 한정되지 않는다: Each of the chrysanthemum extract and the golden extract, which are active ingredients of the present invention, is preferably prepared by a method comprising the following steps, but is not limited thereto:
1) 국화 및 황금 각각에 추출용매를 가하여 추출하는 단계;1) extracting by adding an extraction solvent to each of chrysanthemum and gold;
2) 단계 1)의 추출물을 여과하는 단계;2) filtering the extract of step 1);
3) 단계 2)의 여과물을 감압 농축하는 단계; 및3) concentrating the filtrate of step 2) under reduced pressure; And
4) 단계 3)의 농축물을 건조하는 단계.4) drying the concentrate of step 3).
본 발명의 제조방법에 있어서, 단계 1)의 국화 또는 황금은 재배한 것 또는 시판되는 것을 제한 없이 사용할 수 있다. 또한, 상기 국화는 국화의 꽃, 가지, 줄기, 잎, 열매, 지상부, 뿌리줄기, 뿌리 또는 이들의 조합을 사용할 수 있고, 보다 구체적으로 국화의 꽃을 사용할 수 있으나, 이에 한정되지 않는다.In the production method of the present invention, the chrysanthemum or gold of step 1) may be grown or commercially available without limitation. In addition, the chrysanthemum may be a chrysanthemum flower, branch, stem, leaf, fruit, ground part, rhizome, root, or a combination thereof, and more specifically, a chrysanthemum flower may be used, but is not limited thereto.
본 발명의 제조방법에 있어서, 상기 단계 1)의 추출용매는 물, 알코올 또는 이의 혼합물을 사용하는 것이 바람직하다. 상기 알코올로는 C1 내지 C2의 저급 알코올 이용하는 것이 바람직하며, 저급 알코올로는 에탄올 또는 메탄올을 이용하는 것이 바람직하다. 추출방법으로는 진탕추출, Soxhelt 추출 또는 환류 추출을 이용하는 것이 바람직하나, 이에 한정되지 않는다. 상기 추출용매를 건조된 국화 분량의 1 내지 12배 첨가하여 추출하는 것이 바람직하고, 3 내지 10배 첨가하여 추출하는 것이 보다 바림직하며, 5 내지 8배 첨가하여 추출하는 것이 보다 더 바람직하다. 또한, 상기 추출용매를 건조된 황금 분량의 1 내지 15배 첨가하여 추출하는 것이 바람직하고, 3 내지 13배 첨가하여 추출하는 것이 보다 바람직하며, 8 내지 12배 첨가하여 추출하는 것이 보다 더 바람직하다. 추출 온도는 20℃ 내지 100℃인 것이 바람직하며, 80℃ 내지 100℃인 것이 보다 바람직하나, 이에 한정되지 않는다. 또한, 추출시간은 1 내지 72시간이 바람직하며, 12 내지 48시간이 보다 바람직하고, 20 내지 28시간이 보다 더 바람직하나, 이에 한정되지 않는다. 아울러 추출 횟수는 1 내지 5회인 것이 바람직하며, 3 내지 4회 반복 추출하는 것이 보다 바람직하고, 3회인 것이 보다 더 바람직하나, 이에 한정되지 않는다. In the production method of the present invention, it is preferable to use water, alcohol or a mixture thereof as the extraction solvent in step 1). It is preferable to use C 1 to C 2 lower alcohol as the alcohol, and it is preferable to use ethanol or methanol as the lower alcohol. As the extraction method, it is preferable to use shaking extraction, Soxhelt extraction, or reflux extraction, but is not limited thereto. It is preferable to extract by adding 1 to 12 times the amount of the dried chrysanthemum to the extraction solvent, it is more preferable to extract by adding 3 to 10 times, and even more preferably to extract by adding 5 to 8 times. In addition, it is preferable to extract by adding 1 to 15 times the amount of dried gold to the extraction solvent, more preferably to extract by adding 3 to 13 times, and even more preferably to extract by adding 8 to 12 times. The extraction temperature is preferably from 20°C to 100°C, and more preferably from 80°C to 100°C, but is not limited thereto. In addition, the extraction time is preferably 1 to 72 hours, more preferably 12 to 48 hours, even more preferably 20 to 28 hours, but is not limited thereto. In addition, the number of extractions is preferably 1 to 5 times, more preferably 3 to 4 times of repeated extraction, and even more preferably 3 times, but is not limited thereto.
본 발명의 제조방법에 있어서, 단계 3)의 감압농축은 진공 감압 농축기 또는 진공회전증발기를 이용하는 것이 바람직하나 이에 한정하지 않는다. 또한, 건조는 감압건조, 진공건조, 비등건조, 분무건조 또는 동결건조하는 것이 바람직하나 이에 한정하지 않는다. In the manufacturing method of the present invention, the vacuum concentration in step 3) is preferably a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, the drying is preferably vacuum drying, vacuum drying, boiling drying, spray drying, or freeze drying, but is not limited thereto.
본 발명의 제조방법에 있어서, 상기 국화 추출물 및 황금 추출물은 각각의 추출물을 제조한 후 혼합할 수 있으나, 국화 및 황금을 혼합한 후 이의 추출물을 수득하는 형태로 제조되는 것도 가능하다.In the manufacturing method of the present invention, the chrysanthemum extract and the golden extract may be mixed after preparing each extract, but may be prepared in a form in which an extract thereof is obtained after mixing chrysanthemum and gold.
상기 조성물은 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하는 것이 보다 바람직하고, 국화 추출물 : 황금 추출물을 5.5 : 4.5 내지 7.5 : 2.5의 중량비로 함유하는 것이 보다 더 바람직하고, 6 : 4 내지 7 : 3의 중량비로 함유하는 것이 가장 바람직하나, 이에 한정되지 않는다.The composition is more preferable to contain chrysanthemum extract: golden extract in a weight ratio of 5:5 to 8:2, more preferably contain chrysanthemum extract:gold extract in a weight ratio of 5.5:4.5 to 7.5:2.5, It is most preferably contained in a weight ratio of 6:4 to 7:3, but is not limited thereto.
상기 호흡기 질환은 천식, 기관지염, 폐렴, 기침 또는 가래를 동반하는 폐기종, 기관지 확장증, 폐섬유증 및 만성폐쇄성 폐질환(chronic obstructive pulmonary disease)으로 이루어진 군으로부터 선택되는 어느 하나 이상인 것이 바람직하나 이에 한정되지 않는다.The respiratory disease is preferably any one or more selected from the group consisting of asthma, bronchitis, pneumonia, emphysema with cough or sputum, bronchiectasis, pulmonary fibrosis, and chronic obstructive pulmonary disease, but is not limited thereto. .
상기 혼합 비율로 혼합된 추출물은 기관지 상피세포에서 염증을 억제하고, 염증성 점액단백질의 분비를 억제하는 것이 바람직하다.
It is preferable that the extract mixed at the above mixing ratio inhibits inflammation in bronchial epithelial cells and suppresses the secretion of inflammatory mucous proteins.
본 발명의 구체적인 실시예에서, 본 발명자들은 국화 에탄올 추출물 및 황금 열수 추출물을 제조하고, 상기 추출물을 다양한 혼합 비율로 혼합하여 국화 및 황금 혼합 추출물을 제조하였다.In a specific embodiment of the present invention, the present inventors prepared a chrysanthemum ethanol extract and a golden hot water extract, and mixed the extract in various mixing ratios to prepare a chrysanthemum and golden mixed extract.
또한, 본 발명자들은 염증을 유도한 대식세포에서 상기 국화 및 황금 혼합 추출물의 항염증 효과를 확인한 결과, 본 발명의 혼합 추출물은 세포독성 없이 NO 생성을 유의적으로 억제함을 확인하였다. 또한, 국화 및 황금 혼합 추출물의 혼합 비율이 6 : 4인 경우 NO 생성 억제 효과가 보다 우수함을 확인하였다(도 1 및 도 2 참조).In addition, the present inventors confirmed the anti-inflammatory effect of the mixed extract of chrysanthemum and gold on macrophages induced by inflammation, and confirmed that the mixed extract of the present invention significantly inhibited NO production without cytotoxicity. In addition, when the mixing ratio of the chrysanthemum and golden mixed extract was 6:4, it was confirmed that the NO generation inhibitory effect was more excellent (see FIGS. 1 and 2).
또한, 본 발명자들은 염증성 점액단백질인 MUC5AC 생성을 유도 또는 염증을 유도한 기관지 상피세포에서 상기 국화 및 황금 혼합 추출물의 항염증 효과를 확인한 결과, 본 발명의 혼합 추출물은 세포독성 없이 MUC5AC 분비를 유의적으로 억제하고, 염증 매개 인자인 PGE2 분비를 유의적으로 억제함을 확인하였다. 또한, 국화 및 황금 혼합 추출물의 혼합 비율이 6 : 4인 경우 MUC5AC 및 PGE2 분비 억제 효과가 보다 우수함을 확인하였다(도 3 내지 도 5 참조). In addition, the present inventors confirmed the anti-inflammatory effect of the mixed extract of chrysanthemum and gold in the bronchial epithelial cells that induced the production of the inflammatory mucoprotein MUC5AC or induced inflammation, the mixed extract of the present invention significantly secreted MUC5AC without cytotoxicity. And significantly inhibited the secretion of PGE 2 , an inflammatory mediator. In addition, it was confirmed that the MUC5AC and PGE 2 secretion inhibitory effect was more excellent when the mixing ratio of the chrysanthemum and golden mixed extract was 6:4 (see FIGS. 3 to 5).
또한, 본 발명자들은 알레르기성 천식 마우스 모델에서 상기 국화 및 황금 혼합 추출물이 염증 및 기관지 수축 완화와 면역 불균형 상태 회복을 통해 천식을 개선할 수 있음을 확인하였다. 또한, 국화 및 황금 혼합 추출물의 혼합 비율이 7 : 3인 경우 천식 개선 효과가 보다 우수함을 확인하였다(표 2 내지 4 참조).In addition, the present inventors confirmed that the mixed extract of chrysanthemum and gold in an allergic asthma mouse model can improve asthma by relieving inflammation and bronchial contraction and recovering an immune imbalance. In addition, when the mixing ratio of the mixed extract of chrysanthemum and gold was 7:3, it was confirmed that the asthma improvement effect is more excellent (see Tables 2 to 4).
아울러, 본 발명자들은 미세먼지 유도 마우스 모델에서 상기 국화 및 황금 혼합 추출물이 거담 배출능을 증가시키고, 류코트리엔(leukotriene) 생성량을 감소시켜 미세먼지에 의한 호흡기 질환을 개선할 수 있음을 확인하였다. 또한, 국화 및 황금 혼합 추출물의 혼합 비율이 7 : 3인 경우 미세먼지에 의한 호흡기 질환 개선 효과가 보다 우수함을 확인하였다(표 5 참조).In addition, the present inventors confirmed that the mixed extract of chrysanthemum and gold in the micro-dust-inducing mouse model can improve the respiratory tract disease caused by fine dust by increasing the expectorant discharge ability and reducing the amount of leukotriene produced. In addition, when the mixing ratio of the mixed extract of chrysanthemum and gold was 7:3, it was confirmed that the effect of improving respiratory diseases due to fine dust was more excellent (see Table 5).
따라서, 본 발명자들은 본 발명의 국화 및 황금 혼합 추출물이 세포독성이 없고, 유의적인 항염증 효과를 나타내며, 기관지 세포에서 염증성 점액단백질의 분비를 유의적으로 억제하고, 천식 및 미세먼지에 의한 호흡기 질환 개선 효과가 있음을 확인하였고, 상기 효과가 보다 우수한 국화 및 황금 혼합 추출물의 최적 혼합 비율이 6 : 4 내지 7 :3임을 확인하였으므로, 상기 최적 혼합 비율로 혼합된 혼합 추출물을 기관지염, 천식, 폐렴, 만성 폐쇄성 폐질환 등을 포함하는 호흡기 질환 예방 또는 치료용 조성물의 유효성분으로 유용하게 이용할 수 있다.
Therefore, the present inventors believe that the mixed extract of chrysanthemum and gold of the present invention has no cytotoxicity, exhibits a significant anti-inflammatory effect, significantly inhibits the secretion of inflammatory mucous proteins in bronchial cells, and respiratory diseases caused by asthma and fine dust. It was confirmed that there is an improvement effect, and since it was confirmed that the optimal mixing ratio of the chrysanthemum and golden mixed extract having more excellent effects was 6:4 to 7:3, the mixed extract mixed at the optimal mixing ratio was used for bronchitis, asthma, pneumonia, It can be usefully used as an active ingredient of a composition for preventing or treating respiratory diseases including chronic obstructive pulmonary disease.
또한, 본 발명은 국화 추출물 및 황금 추출물을 유효성분으로 함유하고, 상기 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하는, 진해 또는 거담용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for Jinhae or Geodam containing chrysanthemum extract and golden extract as active ingredients, and containing the chrysanthemum extract: golden extract in a weight ratio of 5:5 to 8:2.
상기 국화 추출물 및 황금 추출물은 상기 호흡기 질환 예방 또는 치료용 조성물에 대한 설명과 동일한 바, 구체적인 설명은 상기 내용을 원용하고, 이하에서는 진해 또는 거담용에 특유한 구성에 대해서만 설명하도록 한다.The chrysanthemum extract and the golden extract are the same as the description of the composition for preventing or treating respiratory diseases, and the detailed description refers to the above, and hereinafter, only the configuration specific to Jinhae or Geodamyong will be described.
상기 "진해"는 기침을 그치게 하는 것을 의미하고, 상기 "거담"은 객담을 배출하는 것을 의미하는 것으로, 기도 내 점액질의 저류를 완화, 개선 또는 치료하는 것을 포함한다. 구체적으로, 상기 거담은 기도, 예컨대 말초 기도에 있는 객담을 중심 기도로 이동 또는 분비를 감소시켜 기침으로 제거하게 하고, 점액 분비를 감소시켜 객담 배출을 용이하게 하는 것을 모두 포함하는 개념이다. The "jinhae" means to stop coughing, and the "expectant" means to discharge sputum, and includes alleviating, ameliorating, or treating the retention of mucus in the airways. Specifically, the expectorant is a concept that includes all of the movement of sputum in the airways, such as the peripheral airways, to the central airway or reducing the secretion to remove it by coughing, and reducing the secretion of mucus to facilitate the discharge of sputum.
상기 조성물은 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하는 것이 보다 바람직하고, 국화 추출물 : 황금 추출물을 5.5 : 4.5 내지 7.5 : 2.5의 중량비로 함유하는 것이 보다 더 바람직하고, 6 : 4 내지 7 : 3의 중량비로 함유하는 것이 가장 바람직하나, 이에 한정되지 않는다.The composition is more preferable to contain chrysanthemum extract: golden extract in a weight ratio of 5:5 to 8:2, more preferably contain chrysanthemum extract:gold extract in a weight ratio of 5.5:4.5 to 7.5:2.5, It is most preferably contained in a weight ratio of 6:4 to 7:3, but is not limited thereto.
또한, 상기 혼합 비율로 혼합된 추출물은 기관지 상피세포에서 염증성 점액단백질의 분비를 억제하고, 이를 통해 진해 효과를 나타내며, 점액단백질 분비 억제를 통해 거담을 용이하게 한다.In addition, the extract mixed in the above mixing ratio inhibits the secretion of inflammatory mucous proteins from bronchial epithelial cells, thereby exhibits antitussive effect, and facilitates expectoration through inhibition of mucous protein secretion.
또한, 본 발명의 조성물은 진해 또는 거담 효과를 나타내므로 기침, 가래 등의 증상을 완화시킬 수 있으므로, 이러한 증상을 수반하는 호흡기 질환의 예방 또는 치료에 유용하게 사용될 수 있다.
In addition, since the composition of the present invention exhibits antitussive or expectorant effects, it can alleviate symptoms such as cough and sputum, and thus can be usefully used in the prevention or treatment of respiratory diseases accompanying these symptoms.
본 발명의 조성물은 경구 또는 비경구 투여(예를 들어, 도포 또는 정맥 내, 피하, 복강 내 주사)할 수 있으나 경구 투여가 바람직하다. 비경구 투여를 위한 제제로는 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 멸균된 수용액, 액제, 비수성용제, 현탁제, 에멀젼, 시럽, 좌제, 에어로졸 등의 외용제 및 멸균 주사제제의 형태로 제형화하여 사용될 수 있으며, 바람직하게는 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 또는 카타플 라스마제의 피부 외용 약학적 조성물을 제조하여 사용할 수 있으나, 이에 한정하는 것은 아니다. 국소 투여의 조성물은 임상적 처방에 따라 무수형 또는 수성형일 수 있다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. 경구 투여를 위한 고형제제에는 산제, 과립제, 정제, 캡슐제, 연질캅셀제, 환 등이 포함된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제, 에어로졸 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.The composition of the present invention may be administered orally or parenterally (eg, application or intravenous, subcutaneous, intraperitoneal injection), but oral administration is preferred. Formulations for parenteral administration include powders, granules, tablets, capsules, sterilized aqueous solutions, solutions, non-aqueous solutions, suspensions, emulsions, syrups, suppositories, aerosols, etc. Formulated in a form and used, preferably, a pharmaceutical composition for skin external use of cream, gel, patch, spray, ointment, warning agent, lotion, liniment, pasta, or cataplasma may be prepared and used. However, it is not limited thereto. Compositions for topical administration may be anhydrous or aqueous, depending on the clinical prescription. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used. Solid preparations for oral administration include powders, granules, tablets, capsules, soft capsules, pills, and the like. Liquid preparations for oral use include suspensions, solvents, emulsions, syrups, aerosols, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as humectants, sweeteners, fragrances, and preservatives are included. I can.
상기 조성물은 투여를 위해서 본 발명의 유효성분 이외에 추가로 약제학적으로 허용 가능한 담체를 1종 이상 포함하여 제조할 수 있다. 약제학적으로 허용 가능한 담체는 식염수, 멸균수, 링거액, 완충 식염수, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형 등으로 제제화할 수 있다.The composition may be prepared by including at least one pharmaceutically acceptable carrier in addition to the active ingredient of the present invention for administration. Pharmaceutically acceptable carriers can be used by mixing saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these ingredients, and if necessary, antioxidants and buffers. , Other conventional additives such as bacteriostatic agents may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to form an injectable formulation such as an aqueous solution, suspension, or emulsion.
본 발명에 따른 약제학적으로 허용가능한 첨가제는 상기 조성물에 대해 0.1 내지 90 중량부로 포함되는 것이 바람직하다.The pharmaceutically acceptable additive according to the present invention is preferably contained in an amount of 0.1 to 90 parts by weight based on the composition.
본 발명의 조성물의 바람직한 투여량은 체내에서 활성성분의 흡수도, 환자의 연령, 성별 및 비만의 정도에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 경구 투여제의 경우 일반적으로 성인에게 1일에 체중 1㎏당 본 발명의 조성물을 1일 0.0001 내지 500 ㎎/㎏으로, 바람직하게는 0.001 내지 300 ㎎/㎏으로, 보다 바람직하게는 0.01 내지 200 mg/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.
The preferred dosage of the composition of the present invention depends on the degree of absorption of the active ingredient in the body, the age, sex, and degree of obesity of the patient, but may be appropriately selected by those skilled in the art. However, for a desirable effect, in the case of oral administration, the composition of the present invention is generally 0.0001 to 500 mg/kg per day for adults, preferably 0.001 to 300 mg/kg, and more preferably for adults. It is recommended to administer 0.01 to 200 mg/kg. Administration may be administered once a day, or may be divided several times. The above dosage does not limit the scope of the present invention in any way.
또한, 본 발명은 국화 추출물 및 황금 추출물을 유효성분으로 함유하고, 상기 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하는, 호흡기 질환 예방 또는 개선용 건강식품을 제공한다.In addition, the present invention provides a health food for preventing or improving respiratory diseases, containing chrysanthemum extract and golden extract as active ingredients, and containing the chrysanthemum extract: golden extract in a weight ratio of 5:5 to 8:2.
아울러, 본 발명은 국화 추출물 및 황금 추출물을 유효성분으로 함유하고, 상기 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하는, 진해 또는 거담용 건강식품을 제공한다.In addition, the present invention provides a health food for Jinhae or Geodam containing chrysanthemum extract and golden extract as active ingredients, and containing the chrysanthemum extract: golden extract in a weight ratio of 5:5 to 8:2.
상기 국화 추출물 및 황금 추출물은 상기 호흡기 질환 예방 또는 치료용 조성물에 대한 설명과 동일한 바, 구체적인 설명은 상기 내용을 원용하고, 이하에서는 건강식품에 특유한 구성에 대해서만 설명하도록 한다.The chrysanthemum extract and the golden extract are the same as the description of the composition for preventing or treating respiratory diseases, and the detailed description uses the above contents, and hereinafter, only the configuration specific to the health food will be described.
한편, 약학적 조성물과 마찬가지로, 본 발명의 국화 및 황금 혼합 추출물이 세포독성이 없고, 유의적인 항염증 효과를 나타내며, 기관지 세포에서 염증성 점액단백질의 분비를 유의적으로 억제하고, 천식 및 미세먼지에 의한 호흡기 질환 개선 효과가 있음을 확인하였으므로, 본 발명의 혼합 추출물을 기관지염, 천식, 폐렴, 만성 폐쇄성 폐질환 등을 포함하는 호흡기 질환 예방 또는 치료용, 진해 또는 거담용 건강식품의 유효성분으로 유용하게 이용할 수 있다.
On the other hand, like the pharmaceutical composition, the mixed extract of chrysanthemum and gold of the present invention has no cytotoxicity, exhibits a significant anti-inflammatory effect, significantly inhibits the secretion of inflammatory mucoproteins from bronchial cells, and prevents asthma and fine dust. Since it was confirmed that there is an effect of improving respiratory diseases, the mixed extract of the present invention is useful as an active ingredient in health food for antitussive or expectorant for preventing or treating respiratory diseases including bronchitis, asthma, pneumonia, and chronic obstructive pulmonary disease. Can be used.
본 발명의 2종의 추출물을 식품 또는 음료 첨가물로 사용할 경우, 상기 2종의 추출물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용되고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 상기 2종의 추출물의 혼합양은 그의 사용목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 건강 및 위생을 목적으로 하거나 또는 건강조절을 목적으로 하는 장기간의 섭취의 경우, 상기 2종의 추출물 추출물은 안전성 면에서 아무런 문제가 없기 때문에, 장기간 복용이 가능하다. 상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 초콜릿류, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있다. 음료수로 제형화할 경우에 상기 2종의 추출물 이외에 첨가되는 액체 성분으로는 이제 한정되지는 않으나, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드(예, 포도당, 과당 등), 디사카라이드(예, 말토오스, 수크로오스 등) 및 폴리사카라이드(예, 덱스트린, 시클로덱스트린 등과 같은 통상적인 당), 및 자일리톨, 소르비톨, 에리스리톨 등의 당 알코올이다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖ 당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다. 상술한 것 이외의 향미제로서 천연 향미제[타우마린, 스테비아 추출물(예, 레바우디오시드 A, 글리시르히진 등)] 및 합성 향미제(예, 사카린, 아스파르탐 등)를 사용할 수 있다.When using the two extracts of the present invention as a food or beverage additive, the two extracts are added as they are or used together with other food or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the two extracts may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment). In the case of long-term intake for the purpose of health and hygiene or for the purpose of health control, the two types of extracts can be taken for a long time because there is no problem in terms of safety. There is no particular limitation on the type of the food. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, and drinks. , Alcoholic beverages and vitamin complexes. When formulated as a beverage, the liquid component added in addition to the above two extracts is not limited anymore, but may contain various flavoring agents or natural carbohydrates as an additional component, as in a conventional beverage. Examples of the above-described natural carbohydrates are monosaccharides (e.g., glucose, fructose, etc.), disaccharides (e.g., maltose, sucrose, etc.) and polysaccharides (e.g., common sugars such as dextrin, cyclodextrin, etc.), and xylitol. , Sorbitol, and sugar alcohols such as erythritol. The proportion of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention. As flavoring agents other than those described above, natural flavoring agents (e.g., taumarin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (eg, saccharin, aspartame, etc.) can be used. .
다른 양태로서, 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 증진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 또한 본 발명의 식품 조성물은 과일 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 단독으로 또는 조합으로 사용될 수 있으며, 이러한 첨가제의 비율은 조성물 전체 중량당 0.001 내지 50 중량부의 범위에서 선택되는 것이 일반적이다.
In another aspect, the food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and enhancing agents (cheese, chocolate, etc.), pectic acid and salts thereof, and organic acids. , A protective colloid thickener, a pH adjuster, a stabilizer, a preservative, a glycerin, an alcohol, a carbonation agent used in carbonated beverages, and the like. In addition, the food composition of the present invention may contain pulp for the production of fruit and vegetable beverages. These components may be used alone or in combination, and the proportion of these additives is generally selected in the range of 0.001 to 50 parts by weight per total weight of the composition.
이하, 본 발명을 실시예, 실험예 및 제조예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail by Examples, Experimental Examples and Preparation Examples.
단, 하기 실시예, 실험예 및 제조예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예, 실험예 및 제조예에 한정되는 것은 아니다.
However, the following Examples, Experimental Examples, and Preparation Examples are merely illustrative of the present invention, and the contents of the present invention are not limited to the following Examples, Experimental Examples, and Preparation Examples.
<< 실시예Example 1> 국화 추출물의 제조 1> Preparation of chrysanthemum extract
국화(Chrysanthemum morifolium Ramatuelle) 원물 50 g에 10배량의 물을 가하여 12시간 동안 95℃에서 추출한 후 여지(Watman grade 2, UK)로 여과한 뒤 농축기(EYELA N-3000, Japan)로 50℃에서 감압농축 및 동결건조하여 열수 추출물을 얻었다. Chrysanthemum ( Chrysanthemum morifolium) Ramatuelle ) 50 g of the raw material was added 10 times the amount of water, extracted at 95°C for 12 hours, filtered through filter paper (
또한, 국화 원물 50 g에 8배량의 70% 에탄올을 가하여 12시간 동안 75℃에서 추출한 후 여지(Watman grade 2, UK)로 여과한 뒤 농축기(EYELA N-3000, Japan)로 50℃에서 감압농축 및 동결건조하여 에탄올 추출물을 얻었다.
In addition, 8 times the amount of 70% ethanol was added to 50 g of the original chrysanthemum, extracted at 75°C for 12 hours, filtered through filter paper (
<< 실시예Example 2> 황금 추출물의 제조 2> Preparation of golden extract
황금(Scutellaria baicalensis Georgi) 원물 50 g에 10배량의 물을 가하여 12시간 동안 95℃에서 추출한 후 여지(Watman grade 2, UK)로 여과한 뒤 농축기(EYELA N-3000, Japan)로 50℃에서 감압농축 및 동결건조하여 열수 추출물을 얻었다. Golden ( Scutellaria baicalensis Georgi ) After adding 10 times the amount of water to 50 g of the raw material, extracting it at 95°C for 12 hours, filtered through filter paper (
또한, 황금 원물 50 g에 8배량의 70% 에탄올을 가하여 12시간 동안 75℃에서 추출한 후 여지(Watman grade 2, UK)로 여과한 뒤 농축기(EYELA N-3000, Japan)로 50℃에서 감압농축 및 동결건조하여 에탄올 추출물을 얻었다.
In addition, 8 times the amount of 70% ethanol was added to 50 g of the original golden material, extracted at 75°C for 12 hours, filtered through filter paper (
<< 실시예Example 3> 국화 및 황금 혼합 추출물의 제조 3> Preparation of mixed extract of chrysanthemum and golden
상기 <실시예 1>에서 제조한 국화 에탄올 추출물 및 <실시예 2>에서 제조한 황금 열수 추출물을 하기 [표 1]의 조성으로 혼합하여 국화 및 황금 혼합 추출물을 제조하였다.The chrysanthemum ethanol extract prepared in <Example 1> and the golden hot water extract prepared in <Example 2> were mixed in the composition of the following [Table 1] to prepare a mixed extract of chrysanthemum and gold.
6:4
6:4
7:3
7:3
8:2
9:1
9:1
<< 실험예Experimental example 1> 대식세포에서 국화 및 황금 혼합 추출물의 항염증 효과 확인 1> Confirmation of anti-inflammatory effect of mixed extract of chrysanthemum and gold on macrophages
<1-1> 대식세포에서 국화 및 황금 혼합 추출물의 세포독성 확인<1-1> Confirmation of cytotoxicity of mixed extract of chrysanthemum and gold in macrophages
상기 <실시예 1>에서 제조한 국화 추출물, <실시예 2>에서 제조한 황금 추출물 및 <실시예 3>에서 제조한 국화 및 황금 혼합 추출물의 세포독성을 확인하기 위하여, 상기 <실시예 1>의 국화 추출물, <실시예 2>의 황금 추출물 또는 <실시예 3>의 국화 및 황금 혼합 추출물을 처리하고 LPS로 염증을 유도한 대식세포에서 세포 생존율을 확인하였다.In order to confirm the cytotoxicity of the chrysanthemum extract prepared in <Example 1>, the golden extract prepared in <Example 2>, and the mixed extract of chrysanthemum and gold prepared in <Example 3>, the <Example 1> The chrysanthemum extract of, the golden extract of <Example 2>, or the mixed extract of chrysanthemum and gold of <Example 3> were treated, and the cell survival rate was confirmed in macrophages induced inflammation with LPS.
구체적으로, 대식세포로 마우스 유래 대식세포주 RAW 264.7 세포를 1×106 세포/㎖로 96-웰 플레이트에 200 ㎕씩 분주하고 37℃, 5% CO2 배양기에서 12시간 동안 배양 배지로 배양하여 세포를 안정화시켰다. 12시간 뒤 배양 배지를 모두 제거하고 새로운 배지로 교체한 후 상기 <실시예 1>에서 제조한 국화 열수 추출물 또는 국화 에탄올 추출물, <실시예 2>에서 제조한 황금 열수 추출물 또는 황금 에탄올 추출물, 또는 <실시예 3>에서 제조한 국화 및 황금 혼합 추출물 시료를 농도별로 20 ㎕씩 처리하고 30분 동안 배양하였다. 이때, 열수 추출물은 증류수에 용해하였고, 에탄올 추출물은 0.2% DMSO에 용해하여 사용하였다. 그 후, LPS(Lipopolysaccharide) 1 ㎍/㎖를 처리하고 24시간 동안 재배양하여 염증을 유도한 다음, cell counting kit-8 (CCK-8) 용액 20 ㎕를 첨가해 450 nm에서 흡광도를 측정하였다. 또한, saline 대조군(DW)은 증류수를 처리하였고. DMSO 대조군(DMSO)은 0.2% DMSO를 처리하였다. 그 다음, 하기 [수학식 1]을 이용하여 시료에 대한 세포생존율을 saline 대조군에 대한 세포생존율(%)로 나타내었다. Specifically, as macrophages, a mouse-derived macrophage line RAW 264.7 cells were dispensed at 1×10 6 cells/ml into a 96-
그 결과, 도 1에 나타낸 바와 같이, LPS만 처리한 RAW 274.7 세포와 비교하여, LPS와 200 ㎍/㎖의 황금 열수 추출물 또는 황금 에탄올 추출물을 동시에 처리한 RAW 274.7 세포의 경우 황금 추출물의 세포 독성으로 인해 세포생존율이 낮게 나타남을 확인하였다(도 1A 및 도 1B). 반면, LPS와 200 ㎍/㎖의 국화 및 황금 혼합 추출물을 동시에 처리한 RAW 274.7 세포의 경우 세포생존율이 높게 나타남을 확인하였다. 특히, LPS와 200 ㎍/㎖의 국화 에탄올 추출물을 동시에 처리한 RAW 274.7 세포보다 세포생존율이 높게 나타나므로, 국화 및 황금 혼합 추출물이 LPS에 의해 유도되는 대식세포 사멸 억제의 시너지 효과가 있음을 확인하였다(도 1C). As a result, as shown in FIG. 1, compared to RAW 274.7 cells treated with only LPS, RAW 274.7 cells treated with LPS and 200 µg/ml of golden hot water extract or golden ethanol extract at the same time caused the cytotoxicity of the golden extract. It was confirmed that the cell viability was low (Fig. 1A and Fig. 1B). On the other hand, it was confirmed that the cell viability was high in the case of RAW 274.7 cells treated with LPS and 200 ㎍/㎖ of chrysanthemum and golden mixed extract at the same time. In particular, since the cell viability was higher than that of RAW 274.7 cells treated with LPS and 200 μg/ml of chrysanthemum ethanol extract at the same time, it was confirmed that the mixed extract of chrysanthemum and gold had a synergistic effect of inhibiting macrophage apoptosis induced by LPS. (Figure 1C).
상기의 결과를 통해 국화 및 황금 혼합 추출물은 세포독성이 없고, 국화 추출물 및 황금 추출물을 모두 포함하여 LPS에 의해 유도되는 대식세포 사멸 억제에 있어서 시너지 효과를 나타냄을 확인하였다.
Through the above results, it was confirmed that the mixed extract of chrysanthemum and gold had no cytotoxicity, and exhibited a synergistic effect in inhibiting macrophage death induced by LPS, including both the chrysanthemum extract and the gold extract.
<1-2> 대식세포에서 국화 및 황금 혼합 추출물의 NO 생성 억제 효과 확인<1-2> Confirmation of NO production inhibitory effect of mixed extract of chrysanthemum and gold in macrophages
국화 및 황금 혼합 추출물의 항염증 활성을 알아보기 위하여, 상기 <실시예 1>에서 제조한 국화 추출물, <실시예 2>에서 제조한 황금 추출물 또는 <실시예 3>에서 제조한 국화 및 황금 혼합 추출물을 처리하고 LPS로 염증을 유도한 대식세포에서 생성되는 NO의 양을 Green 등의 방법에 따라 griess 시약을 이용하여 세포배양액 중에 존재하는 NO2의 형태로 측정하였다. In order to examine the anti-inflammatory activity of the chrysanthemum and golden mixed extract, the chrysanthemum extract prepared in <Example 1>, the golden extract prepared in <Example 2>, or the mixed chrysanthemum and golden extract prepared in <Example 3> The amount of NO generated in macrophages induced inflammation with LPS was measured in the form of NO 2 present in the cell culture solution using griess reagent according to the method of Green et al.
구체적으로, 6-웰 플레이트에 RAW 264.7 세포를 1 × 105 세포/㎖로 분주하였다. 37℃ CO2 배양기에서 24시간 배양한 이후 1×PBS로 2번 세척하였다. 그런 다음, LPS 1 ㎍/㎖를 2시간 동안 처리한 후, 상기 <실시예 1>에서 제조한 국화 열수 추출물 또는 국화 에탄올 추출물, <실시예 2>에서 제조한 황금 열수 추출물 또는 황금 에탄올 추출물, 또는 <실시예 3>에서 제조한 국화 및 황금 혼합 추출물 시료를 농도별로 처리하고 24시간 배양한 다음 상등액을 획득하였다. 그 다음, 동량의 griess 시약을 첨가하여 96-웰 플레이트에서 10분간 반응시킨 후 540 nm에서의 흡광도를 측정하였다. 그 다음, 하기 [수학식 2]를 이용하여 NO 억제 활성능을 계산하였다.Specifically, RAW 264.7 cells were dispensed into a 6-well plate at 1 × 10 5 cells/ml. After incubation for 24 hours in a 37° C. CO 2 incubator, it was washed twice with 1×PBS. Then, after treatment with 1 ㎍ / ㎖ LPS for 2 hours, the chrysanthemum hot water extract or the chrysanthemum ethanol extract prepared in <Example 1>, the golden hot water extract or the golden ethanol extract prepared in <Example 2>, or The chrysanthemum and golden mixed extract samples prepared in <Example 3> were treated by concentration, cultured for 24 hours, and then a supernatant was obtained. Then, the same amount of griess reagent was added and reacted in a 96-well plate for 10 minutes, and the absorbance at 540 nm was measured. Then, the NO inhibitory activity was calculated using the following [Equation 2].
그 결과, 도 2에 나타낸 바와 같이, LPS와 200 ㎍/㎖의 황금 열수 추출물 또는 황금 에탄올 추출물을 동시에 처리한 RAW 274.7 세포의 경우 세포독성으로 인해 세포 생존율이 감소하여, NO 생성이 감소하는 것을 확인하였다(도 2A 및 도 2B). 반면, LPS와 국화 및 황금 혼합 추출물을 동시에 처리한 RAW 274.7 세포의 경우 세포독성 없이 NO 생성이 감소하는 것을 확인하였다. 특히, LPS와 국화 에탄올 추출물을 동시에 처리한 RAW 274.7 세포보다 NO 생성이 감소하므로, 국화 및 황금 혼합 추출물이 LPS에 의해 유도되는 NO 생성 억제의 시너지 효과가 있음을 확인하였다. 또한, 국화 및 황금 혼합 추출물의 혼합 비율이 6:4인 경우 NO 생성 억제 효과가 보다 우수함을 확인하였다(도 2C). As a result, as shown in Figure 2, in the case of RAW 274.7 cells treated with LPS and 200 μg/ml of golden hot water extract or golden ethanol extract at the same time, it was confirmed that the cell viability decreased due to cytotoxicity, thereby reducing NO production. (Fig. 2A and Fig. 2B). On the other hand, in the case of RAW 274.7 cells treated with LPS, chrysanthemum and gold mixed extract at the same time, it was confirmed that NO production was reduced without cytotoxicity. In particular, it was confirmed that NO production was reduced compared to RAW 274.7 cells treated with LPS and ethanol extract of chrysanthemum at the same time, so that the mixed extract of chrysanthemum and gold had a synergistic effect of inhibiting NO production induced by LPS. In addition, when the mixing ratio of the mixed extract of chrysanthemum and gold was 6:4, it was confirmed that the NO generation inhibitory effect was more excellent (FIG. 2C).
상기의 결과를 통해 국화 및 황금 혼합 추출물은 세포독성 없이 NO 생성을 억제하여 우수한 항염증 효과를 나타내고, 국화 추출물 및 황금 추출물을 모두 포함하여 항염증에 있어서 시너지 효과를 나타냄을 확인하였다. 또한, 국화 및 황금 혼합 추출물의 혼합 비율이 6:4인 경우 보다 우수한 항염증 효과를 나타냄을 확인하였다.
Through the above results, it was confirmed that the mixed extract of chrysanthemum and gold exhibited excellent anti-inflammatory effect by inhibiting NO production without cytotoxicity, and exhibited a synergistic effect in anti-inflammatory, including both chrysanthemum extract and gold extract. In addition, it was confirmed that the mixing ratio of the mixed extract of chrysanthemum and gold was 6:4, exhibiting superior anti-inflammatory effect.
<< 실험예Experimental example 2> 인간 유래 기관지 상피세포에서 국화 및 황금 혼합 추출물의 항염증 효과 확인 2> Confirmation of anti-inflammatory effect of mixed extract of chrysanthemum and gold on human-derived bronchial epithelial cells
<2-1> 인간 유래 기관지 상피세포에서 국화 및 황금 혼합 추출물의 세포독성 확인<2-1> Confirmation of Cytotoxicity of Chrysanthemum and Golden Mixed Extracts in Human-derived Bronchial Epithelial Cells
기관지 상피세포에서 상기 <실시예 1>에서 제조한 국화 추출물, <실시예 2>에서 제조한 황금 추출물 및 <실시예 3>에서 제조한 국화 및 황금 혼합 추출물의 세포독성을 확인하기 위하여, 상기 <실시예 1>의 국화 추출물, <실시예 2>의 황금 추출물 또는 <실시예 3>의 국화 및 황금 혼합 추출물을 처리하고 LPS 및 PMA(phorbol 12-myristate 13-acetate)로 MUC5AC 분비를 유도한 기관지 상피세포에서 세포 생존율을 확인하였다.In order to confirm the cytotoxicity of the chrysanthemum extract prepared in <Example 1>, the golden extract prepared in <Example 2>, and the mixed extract of chrysanthemum and gold prepared in <Example 3> in bronchial epithelial cells, the < Bronchial tubes treated with the chrysanthemum extract of Example 1>, the golden extract of Example 2, or the mixed extract of chrysanthemum and gold of Example 3 and induced MUC5AC secretion with LPS and PMA (phorbol 12-myristate 13-acetate) Cell viability was confirmed in epithelial cells.
구체적으로, 기관지 상피세포로 인간 유래 기관지 상피세포주 NCI-H292 세포를 4×104 세포/㎖로 24-웰 플레이트에 500 ㎕씩 분주하고 37℃, 5% CO2 배양기에서 48시간 동안 배양 배지로 배양하여 세포를 안정화시켰다. 48시간 뒤 배양 배지를 모두 제거하고 0.2% FBS/DMEM 배지로 교체한 후 24시간 동안 배양하였다. 그 다음, PBS로 2번 세척하고, 무혈청 배지 400 ㎕와 농도별로 희석한 상기 <실시예 1>의 국화 에탄올 추출물, <실시예 2>의 황금 열수 추출물, 또는 <실시예 3>의 국화 및 황금 혼합 추출물 시료 50 ㎕를 처리하고 1시간 동안 배양하였다. 그 후, 100 ng/㎖ 농도의 PMA 및 20 ㎍/㎖ 농도의 LPS를 처리하고 24시간 동안 재배양하여 MUC5AC의 생성을 유도한 다음, 상기 실험예 <1-1>에 기재된 방법과 동일한 방법으로 세포생존율을 측정하였다. 또한, 상기 실험예 <1-1>을 통해 황금 추출물 단독의 경우 세포 독성이 나타남을 확인하였는바, 이를 고려하여 황금 추출물은 단독으로 최대 100 ㎍/㎖까지 처리하였다.Specifically, as bronchial epithelial cells, human-derived bronchial epithelial cell line NCI-H292 cells were dispensed at 4×10 4 cells/ml into a 24-well plate at 500 μl each, and cultured in a culture medium at 37° C. and 5% CO 2 for 48 hours. Cells were stabilized by culturing. After 48 hours, all the culture medium was removed, replaced with 0.2% FBS/DMEM medium, and cultured for 24 hours. Then, washed twice with PBS and diluted by concentration with 400 μl of serum-free medium, the ethanol extract of the chrysanthemum of <Example 1>, the golden hot water extract of <Example 2>, or the chrysanthemum of <Example 3> and 50 µl of the golden mixed extract sample was treated and incubated for 1 hour. Thereafter, PMA at a concentration of 100 ng/ml and LPS at a concentration of 20 μg/ml were treated and cultivated for 24 hours to induce the production of MUC5AC, and then in the same manner as described in Experimental Example <1-1>. Cell viability was measured. In addition, it was confirmed through the Experimental Example <1-1> that the golden extract alone exhibited cytotoxicity. Taking this into account, the golden extract was treated to a maximum of 100 μg/ml alone.
그 결과, 도 3에 나타낸 바와 같이, LPS 및 PMA만 처리한 NCI-H292 세포와 비교하여, LPS 및 PMA와 함께 100 ㎍/㎖의 황금 열수 추출물을 처리한 NCI-H292 세포의 경우 약한 세포독성이 나타남을 확인하였다. 반면, LPS 및 PMA와 함께 국화 및 황금 혼합 추출물을 동시에 처리한 NCI-H292 세포의 경우 세포생존율이 높게 나타남을 확인하였다(도 3). As a result, as shown in FIG. 3, compared to NCI-H292 cells treated with only LPS and PMA, NCI-H292 cells treated with 100 µg/ml of golden hot water extract together with LPS and PMA showed weak cytotoxicity. It was confirmed that it appeared. On the other hand, it was confirmed that NCI-H292 cells treated with the mixed extract of chrysanthemum and gold together with LPS and PMA showed high cell viability (FIG. 3).
상기의 결과를 통해 기관지 상피세포에서도 국화 및 황금 혼합 추출물은 세포독성이 없음을 확인하였다.
Through the above results, it was confirmed that the mixed extract of chrysanthemum and gold was not cytotoxic even in bronchial epithelial cells.
<2-2> 인간 유래 기관지 상피세포에서 국화 및 황금 혼합 추출물의 염증성 점액단백질 생성 억제 확인<2-2> Confirmation of Inhibition of Inflammatory Mucoprotein Production by Mixed Extract of Chrysanthemum and Gold in Human-derived Bronchial Epithelial Cell
MUC5AC(Mucin 5AC)는 염증성 점액단백질로, LPS와 같은 물질의 자극에 의해 분비되며, 이들의 과다분비는 만성 폐쇄성 폐질환(chronic obstructive pulmonary disease, COPD)을 유발하는 것으로 알려져 있다. 이에, 기관지 상피세포에서 국화 및 황금 혼합 추출물의 MUC5AC 억제 활성을 알아보기 위하여, 상기 <실시예 1>의 국화 추출물, <실시예 2>의 황금 추출물 또는 <실시예 3>의 국화 및 황금 혼합 추출물을 처리하고 LPS 및 PMA로 MUC5AC 분비를 유도한 기관지 상피세포에서 MUC5AC의 분비량을 sandwitch ELISA법을 이용하여 측정하였다.MUC5AC (Mucin 5AC) is an inflammatory mucoprotein and is secreted by stimulation of substances such as LPS, and their oversecretion is known to cause chronic obstructive pulmonary disease (COPD). Thus, in order to investigate the MUC5AC inhibitory activity of the chrysanthemum and golden mixed extract in bronchial epithelial cells, the chrysanthemum extract of <Example 1>, the golden extract of <Example 2> or the mixed chrysanthemum and golden extract of <Example 3> The amount of secretion of MUC5AC in bronchial epithelial cells inducing MUC5AC secretion with LPS and PMA was measured using the sandwitch ELISA method.
구체적으로, 상기 실험예 <2-1>에 기재된 방법과 동일한 방법으로 NCI-H292 세포에 상기 <실시예 1>의 국화 에탄올 추출물, <실시예 2>의 황금 열수 추출물, 또는 <실시예 3>의 국화 및 황금 혼합 추출물 시료를 농도별로 처리하고 LPS 및 PMA로 MUC5AC의 생성을 유도하였다. 그 다음, 배양 상등액만을 취하여, MUC5AC 분비량을 측정하였다.Specifically, the chrysanthemum ethanol extract of <Example 1>, the golden hot water extract of <Example 2>, or <Example 3> of the NCI-H292 cells in the same manner as described in Experimental Example <2-1>. Chrysanthemum and golden mixed extract samples were treated by concentration, and the production of MUC5AC was induced with LPS and PMA. Then, only the culture supernatant was taken, and the amount of secretion of MUC5AC was measured.
그 결과, 도 4에 나타낸 바와 같이, PMA 및 LPS에 의해 유도된 MUC5AC의 분비가 국화 및 황금 혼합 추출물에 의해 억제됨을 확인하였다. 또한, 40 ㎍/㎖ 이상농도의 국화 에탄올 추출물을 단독으로 처리한 군과 비교하여, 40 ㎍/㎖ 이상 농도의 국화 및 황금 혼합 추출물을 처리한 군의 경우 MUC5AC의 분비 억제 효과가 현저히 우수하게 나타나므로, 국화 및 황금 혼합 추출물이 시너지 효과가 있음을 확인하였다. 아울러, 국화 및 황금 혼합 추출물의 혼합 비율이 6:4인 경우 MUC5AC의 분비 억제 효과가 보다 우수함을 확인하였다(도 4).As a result, as shown in Fig. 4, it was confirmed that the secretion of MUC5AC induced by PMA and LPS was inhibited by the mixed extract of chrysanthemum and gold. In addition, compared to the group treated with the ethanol extract of chrysanthemum at a concentration of 40 µg/mL or higher, the group treated with the mixed extract of chrysanthemum and gold at a concentration of 40 µg/mL or higher showed remarkably excellent suppression of secretion of MUC5AC. Therefore, it was confirmed that the mixed extract of chrysanthemum and golden has a synergistic effect. In addition, it was confirmed that the secretion inhibitory effect of MUC5AC was more excellent when the mixing ratio of the chrysanthemum and golden mixed extract was 6:4 (FIG. 4).
상기의 결과를 통해 국화 및 황금 혼합 추출물은 세포독성 없이 MUC5AC 분비를 억제하여 과도한 가래 분비를 억제할 수 있고, 국화 추출물 및 황금 추출물을 모두 포함하여 시너지 효과를 나타냄을 확인하였다. 또한, 국화 및 황금 혼합 추출물의 혼합 비율이 6:4인 경우 보다 우수한 MUC5AC 억제 활성 효과를 나타냄을 확인하였다.
Through the above results, it was confirmed that the mixed extract of chrysanthemum and golden can suppress the secretion of MUC5AC without cytotoxicity, thereby suppressing excessive sputum secretion, and exhibit a synergistic effect including both the chrysanthemum extract and the golden extract. In addition, it was confirmed that the mixing ratio of the mixed extract of chrysanthemum and gold was 6:4, exhibiting a better MUC5AC inhibitory activity effect.
<2-3> 인간 유래 기관지 상피세포에서 국화 및 황금 혼합 추출물의 염증 매개 인자 생성 억제 효과 확인<2-3> Confirmation of the inhibitory effect on the production of inflammatory mediators by mixed extract of chrysanthemum and gold in human bronchial epithelial cells
PGE2(Prostaglandin E2)는 염증을 매개하는 물질로 폐조직의 섬유화(fibrosis)에 관여하는 것으로 잘 알려져 있다. 이에, 기관지 상피세포에서 국화 및 황금 혼합 추출물의 항염증 활성을 알아보기 위하여, 상기 <실시예 1>의 국화 추출물, <실시예 2>의 황금 추출물 또는 <실시예 3>의 국화 및 황금 혼합 추출물을 처리하고 LPS 및 PMA로 MUC5AC 분비를 유도한 기관지 상피세포에서 PGE2 분비량을 sandwitch ELISA법을 이용하여 측정하였다.PGE 2 (Prostaglandin E2) is a substance that mediates inflammation and is well known to be involved in fibrosis of lung tissue. Thus, in order to examine the anti-inflammatory activity of the chrysanthemum and golden mixed extract in bronchial epithelial cells, the chrysanthemum extract of <Example 1>, the golden extract of <Example 2>, or the mixed chrysanthemum and golden extract of <Example 3> The amount of PGE 2 secretion in bronchial epithelial cells inducing MUC5AC secretion with LPS and PMA was measured using the sandwitch ELISA method.
구체적으로, 기관지 상피세포로 인간 유래 기관지 상피세포주 A549 세포를 1×105 세포/㎖로 96-웰 플레이트에 200 ㎕씩 분주하고 37℃, 5% CO2 배양기에서 24시간 동안 배양 배지로 배양하여 세포를 안정화시켰다. 24시간 뒤 배양 배지를 모두 제거하고 0.2% FBS/DMEM 배지로 교체한 후 24시간 동안 배양하였다. 그 다음, PBS로 2번 세척하고, 무혈청 배지 160 ㎕와 농도별로 희석한 상기 <실시예 1>의 국화 에탄올 추출물, <실시예 2>의 황금 열수 추출물 또는 <실시예 3>의 국화 및 황금 혼합 추출물 시료 20 ㎕를 처리하고 30분 동안 배양하였다. 그 후, 20 또는 100 ng/㎖ 농도의 PMA 처리하고 24시간 동안 재배양하여 염증을 유도한 다음, 배양 상등액만을 취하여, PGE2 분비량을 측정하였다.Specifically, as bronchial epithelial cells, 200 µl of human-derived bronchial epithelial cell line A549 cells were dispensed into a 96-well plate at 1×10 5 cells/ml and cultured in a culture medium for 24 hours in a 37°C, 5% CO 2 incubator. Stabilized cells. After 24 hours, all the culture medium was removed, replaced with 0.2% FBS/DMEM medium, and cultured for 24 hours. Then, washed twice with PBS, and diluted by concentration with 160 µl of serum-free medium, the ethanol extract of chrysanthemum of <Example 1>, the golden hot water extract of <Example 2>, or the chrysanthemum and gold of <Example 3> 20 µl of the mixed extract sample was treated and incubated for 30 minutes. Thereafter, PMA treatment at a concentration of 20 or 100 ng/ml and cultivation was performed for 24 hours to induce inflammation, and then only the culture supernatant was taken, and the amount of PGE 2 secretion was measured.
그 결과, 도 5에 나타낸 바와 같이, PMA에 의해 유도된 PGE2의 분비가 국화 및 황금 혼합 추출물에 의해 억제됨을 확인하였다. 또한, 국화 에탄올 추출물을 단독으로 처리한 군과 비교하여, 국화 및 황금 혼합 추출물을 처리한 군의 경우 PGE2의 분비 억제 효과가 현저히 우수하게 나타나므로, 국화 및 황금 혼합 추출물이 시너지 효과가 있음을 확인하였다. 아울러, 국화 및 황금 혼합 추출물의 혼합 비율이 6:4인 경우 PGE2의 분비 억제 효과가 가장 우수함을 확인하였다(도 5).As a result, as shown in FIG. 5, it was confirmed that the secretion of PGE 2 induced by PMA was inhibited by the mixed extract of chrysanthemum and gold. In addition, compared with the group treated with the chrysanthemum ethanol extract alone, the group treated with the chrysanthemum and golden mixed extract showed remarkably excellent secretion inhibitory effect of PGE 2 , so that the mixed extract of chrysanthemum and gold had a synergistic effect. Confirmed. In addition, it was confirmed that the secretion inhibitory effect of PGE 2 was the most excellent when the mixing ratio of the chrysanthemum and golden mixed extract was 6:4 (FIG. 5).
상기의 결과를 통해 국화 및 황금 혼합 추출물은 세포독성 없이 PGE2 분비를 억제하여 폐섬유화를 억제할 수 있고, 국화 추출물 및 황금 추출물을 모두 포함하여 시너지 효과를 나타냄을 확인하였다. 또한, 국화 및 황금 혼합 추출물의 혼합 비율이 6:4인 경우 보다 우수한 항염증 효과를 나타냄을 확인하였다.
Through the above results, it was confirmed that the mixed extract of chrysanthemum and golden can inhibit the secretion of PGE 2 without cytotoxicity, thereby inhibiting lung fibrosis, and exhibit a synergistic effect including both the chrysanthemum extract and the golden extract. In addition, it was confirmed that the mixing ratio of the mixed extract of chrysanthemum and gold was 6:4, exhibiting superior anti-inflammatory effect.
<< 실험예Experimental example 3> 알레르기성 천식 마우스 모델에서 국화 및 황금 혼합 추출물의 항천식 효과 확인 3> Confirmation of anti-asthma effect of mixed extract of chrysanthemum and gold in allergic asthma mouse model
<3-1> 알레르기성 천식 마우스 모델 제작 및 국화 및 황금 혼합 추출물 투여<3-1> Allergic Asthma Mouse Model Preparation and Chrysanthemum and Golden Mixed Extract Administration
실험동물인 수컷 5주령의 BALB/c 수컷 생쥐(20∼22 g)를 ㈜샘타코에서 공급받아 실험 당일까지 충분한 고형사료(Envigo, U.K.)와 물을 공급하고 온도 22 ± 2℃, 습도 55 ± 15%, 12시간-12시간(light-dark cycle)의 환경에서 2주간 적응시킨 뒤 실험에 사용하였다. 본 실험은 대전대학교 동물실험윤리 위원회로부터 승인(동물사용 윤리위원회 승인번호.DJUARB2017-018)을 받아 동물윤리준칙에 의거하여 실험하였다.An experimental animal, male 5-week-old BALB/c male mice (20∼22 g), was supplied from Samtaco Co., Ltd. and supplied with sufficient solid feed (Envigo, UK) and water until the day of the experiment, and a temperature of 22 ± 2℃ and a humidity of 55 ± It was used in the experiment after acclimating for 2 weeks in an environment of 15%, 12 hours-12 hours (light-dark cycle). This experiment was approved by the Animal Experimental Ethics Committee of Daejeon University (approval number of the Animal Use Ethics Committee.DJUARB2017-018) and was conducted in accordance with the Animal Ethics Code.
알레르기성 천식 마우스 모델을 제작하기 위해 먼저, 난알부민(ovalbumin, chicken egg albumin; OVA) 1 ㎎을 PBS와 수산화알루미늄 겔 [Al(OH)3 gel]을 1:1 비율로 혼합한 용액을 0.3 ㎖씩 실험 시작일로부터 7일 간격으로 하루에 1번 각 1회씩 마우스에게 복강으로 주사하였다. 또한 마지막 복강 주사 7일 후인 21일째부터 마우스를 50×15×50 ㎝ 크기의 아크릴상자 안에 넣고 2 ㎎/㎖ OVA 용액 50 ㎖를 네블라이저(nebulizer) 기기를 이용하여 격일(21, 23, 25, 27, 29일째) 간격으로 1일 1회(30분)로 설정하여 분사함으로써 호흡을 통한 천식을 유발하였다. 실험군은 아무것도 처리하지 않는 정상군과 천식 유발을 진행하면서 증류수를 경구 투여하는 대조군, 상기 <실시예 3>의 국화 및 황금 혼합 추출물로서 6:4, 7:3, 8:2 비율로 혼합한 시료를 50, 100, 200 ㎎/㎏으로 경구투여하는 실험군 등 총 11개 그룹으로 나누어 복강 내 주사 후부터 2주간 진행하였다.
To make a mouse model for allergic asthma, first, 0.3 ml of a solution of 1 mg of ovalbumin (chicken egg albumin; OVA) in a 1:1 ratio of PBS and aluminum hydroxide gel [Al(OH) 3 gel] Each mouse was injected intraperitoneally once a day at intervals of 7 days from the start of the experiment. In addition, from the 21st day, 7 days after the last intraperitoneal injection, the mouse was placed in an acrylic box of 50×15×50 cm, and 50 ml of 2 mg/ml OVA solution was added every other day (21, 23, 25, etc.) using a nebulizer device. Asthma was induced through breathing by setting and spraying once a day (30 minutes) at intervals (27th and 29th days). The experimental group was a control group to which distilled water was orally administered while inducing asthma while a normal group was treated with nothing, and a mixture of chrysanthemum and golden extracts of <Example 3> in a ratio of 6:4, 7:3, and 8:2 Was divided into 11 groups, including the experimental group administered orally at 50, 100, and 200 mg/kg, and proceeded for 2 weeks after the intraperitoneal injection.
<3-2> 국화 및 황금 혼합 추출물의 <3-2> Chrysanthemum and golden mixed extract 항천식Anti-asthma 효과 확인 Check the effect
국화 및 황금 혼합 추출물의 항천식 효과를 확인하기 위하여, 알레르기성 천식 마우스 모델에 국화 및 황금 혼합 추출물을 투여한 후, 혈액 및 폐와 기관지 폐포세척액(BALF, bronchoalveolar lavage fluid) 내 면역세포 수를 측정하고, 혈청 및 BALF 내 사이토카인, 난알부민-특이 IgE, 히스타민, TGF-β1, TSLP 및 LTB4 생성량을 측정하였다.In order to confirm the anti-asthma effect of the mixed extract of chrysanthemum and gold, after administering the mixed extract of chrysanthemum and gold to a mouse model of allergic asthma, the number of immune cells in blood and lung and bronchoalveolar lavage fluid (BALF) was measured. And, cytokines, egg albumin-specific IgE, histamine, TGF-β1, TSLP and LTB 4 production levels in serum and BALF were measured.
구체적으로, 상기 실험예 <3-1>에 기재된 방법과 동일한 방법으로 알레르기성 천식 마우스 모델을 제작하고, 국화 및 황금 혼합 추출물을 투여하여 실험을 진행하였다.Specifically, an allergic asthma mouse model was prepared by the same method as described in Experimental Example <3-1>, and an experiment was conducted by administering a mixed extract of chrysanthemum and gold.
혈액 내 면역세포 수를 측정하기 위하여, 실험 종료 후 심장 천자법을 이용하여 채혈한 전혈을 시험검사 기관인 KPNT(Cheongju, Korea)에 백혈구와 호산구, 호중구, 호염기구, 림프구, 단핵구 수를 의뢰하여 분석하였다.In order to measure the number of immune cells in the blood, whole blood collected by cardiac puncture after the end of the experiment was analyzed by requesting the number of leukocytes, eosinophils, neutrophils, basophils, lymphocytes, and monocytes to the test laboratory KPNT (Cheongju, Korea). I did.
또한, BALF 내 총 면역세포 수를 측정하기 위하여, 실험 종료 후 기관지 부분을 해부하였다. 폐포 세척액으로부터 세포를 분리하기 위해 24 G catheter를 기관지(trachea)에 주입시키고 의료용 봉합사로 묶어 고정한 후 배양액을 넣은 실린지를 연결하여 3회 순환시켜 BALF를 획득하였다. 획득한 BALF에 ACK(Ammonium-Chloride-Potassium) 용해 버퍼(lysis buffer) 100 ㎕를 넣어 37℃에서 5분 동안 처리하여 적혈구를 용해시켰다. 이를 다시 배지로 세척한 후 0.04% 트립판 블루(trypan blue)로 염색한 후 총 면역세포 수를 측정하였다.In addition, in order to measure the total number of immune cells in the BALF, the bronchial section was dissected after the end of the experiment. In order to separate cells from the alveolar lavage fluid, a 24 G catheter was injected into the trachea, tied with medical sutures, fixed, and then connected to a syringe containing the culture solution and circulated three times to obtain BALF. To the obtained BALF, 100 µl of ACK (Ammonium-Chloride-Potassium) lysis buffer was added and treated at 37° C. for 5 minutes to lyse red blood cells. This was washed again with medium, stained with 0.04% trypan blue, and then the total number of immune cells was measured.
또한, 실험 종료 후 에틸에테르(ethyl ether)로 마취한 상태에서 심장 천자법으로 채혈한 다음 혈액을 15분간 3,000 rpm에서 원심 분리해서 혈청을 분리하였고, 분리한 BALF 세포를 5×105 세포로 조정한 후 10% FBS를 포함한 DMEM 배지를 사용하여 37℃, 5% CO2 조건이 유지되는 세포배양기에서 24시간 동안 배양하였다. 이후, 배양액을 1,200 rpm에서 5분간 원심 분리해서 상등액을 분리하였다.In addition, after the end of the experiment, blood was collected by cardiac puncture under anesthesia with ethyl ether, and then the blood was centrifuged at 3,000 rpm for 15 minutes to separate the serum, and the separated BALF cells were adjusted to 5×10 5 cells. After that, the cells were cultured for 24 hours in a cell incubator maintained at 37°C and 5% CO2 using DMEM medium containing 10% FBS. Thereafter, the culture solution was centrifuged at 1,200 rpm for 5 minutes to separate the supernatant.
혈청 및 BALF 내 사이토카인 생성량을 측정하기 위하여, 상기와 같이 분리한 혈청, 상등액에서 Mouse cytokine milliplex map immunoassay kit(Millipore Co., U.S.A.)를 이용하여 제조사의 절차에 따라 사이토카인 IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, TNF-α, IFN-γ, IL-17A, IL-17F, IL-17E 생성량을 분석하였다.To measure the amount of cytokine production in serum and BALF, cytokine IL-1β, IL- using Mouse cytokine milliplex map immunoassay kit (Millipore Co., USA) from the serum and supernatant separated as described above according to the manufacturer's procedure. 2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, TNF-α, IFN-γ, IL-17A, IL-17F, IL-17E production amount Was analyzed.
혈청 및 BALF 내 난알부민-특이 IgE 생성량을 측정하기 위하여, 상기와 같이 분리한 혈청, 상등액에서 Mouse OVA specific IgE ELISA kit(Biolegend Co., U.S.A.)를 이용하여 제조사의 절차에 따라 난알부민-특이 IgE 생성량을 분석하였다.To measure the amount of egg albumin-specific IgE produced in serum and BALF, egg albumin-specific IgE according to the manufacturer's procedure using Mouse OVA specific IgE ELISA kit (Biolegend Co., USA) from the serum and supernatant separated as described above. The production amount was analyzed.
혈청 및 BALF 내 히스타민 생성량을 측정하기 위하여, 상기와 같이 분리한 혈청 상등액과 standard를 100 ㎕씩 각 웰에 분주하고 10 ㎕의 balance solution과 50 ㎕의 conjugate를 넣어 1시간 동안 37℃에서 반응시켰다. washing buffer를 이용하여 5회 세척 후 substrate A와 B를 각각 50 ㎕씩 넣어 15분 동안 37℃에서 반응시키고 50 ㎕의 stop solution을 추가하여 450 ㎚에서 흡광도를 측정하였다.In order to measure the amount of histamine production in serum and BALF, 100 µl of the serum supernatant and standard separated as described above were dispensed into each well, and 10 µl of balance solution and 50 µl of conjugate were added and reacted at 37°C for 1 hour. After washing 5 times using a washing buffer, 50 µl each of substrates A and B were added to react at 37°C for 15 minutes, and 50 µl of stop solution was added to measure absorbance at 450 nm.
혈청 및 BALF 내 TGF-β 생성량을 측정하기 위하여, 상기와 같이 분리한 혈청 40 ㎕에 1 N HCl을 10 ㎕씩 넣어 10분 동안 상온에서 반응시킨 후 1.2 N NaOH/0.5 M HEPES를 10 ㎕씩 추가로 넣어 혈청을 활성화시키고, 상기와 같이 분리한 상등액은 100 ㎕에 1 N HCl을 20 ㎕씩 넣어 10분 동안 상온에서 반응시킨 후 1.2 N NaOH/0.5 M HEPES를 20 ㎕씩 추가로 넣어 상등액을 활성화시켰다. 활성화시킨 혈청, 상등액과 standard를 50 ㎕씩 각 웰에 분주하고 RD1-73 시약을 50 ㎕씩 가하여 혼합한 후 2시간 동안 상온에서 plate shaker를 이용하여 혼합하였다. washing buffer를 이용해 4회 세척한 후 TGF-β1 conjugate를 100 ㎕씩 넣고 2시간 동안 상온에서 plate shaker를 이용하여 혼합하였다. 다시 4회 세척 후 substrate solution을 100 ㎕씩 넣어 30분 동안 상온에서 빛을 차단한 채 반응시켰다. 마지막으로 stop solution 100 ㎕를 넣고 450 ㎚에서 흡광도를 측정하였다.In order to measure the amount of TGF-β production in serum and BALF, 10 µl of 1 N HCl was added to 40 µl of serum separated as above and reacted at room temperature for 10 minutes, and then 1.2 N NaOH/0.5 M HEPES was added by 10 µl each. Add 20 µl of 1 N HCl to 100 µl of the supernatant and react at room temperature for 10 minutes, then add 20 µl of 1.2 N NaOH/0.5 M HEPES to activate the supernatant. Made it. 50 µl of activated serum, supernatant, and standard were dispensed into each well, 50 µl of RD1-73 reagent was added and mixed, and then mixed using a plate shaker at room temperature for 2 hours. After washing 4 times using a washing buffer, 100 µl of TGF-β1 conjugate was added and mixed using a plate shaker at room temperature for 2 hours. After washing again 4 times, 100 µl of the substrate solution was added and reacted at room temperature for 30 minutes while blocking the light. Finally, 100 µl of the stop solution was added and the absorbance was measured at 450 nm.
혈청 및 BALF 내 TSLP 생성량을 측정하기 위하여, 상기와 같이 분리한 혈청, 상등액과 standard를 50 ㎕씩 각 well에 분주하고 RD1-21 시약을 50 ㎕씩 가하여 혼합한 후 2시간 동안 상온에서 반응시켰다. washing buffer를 이용해 5회 세척한 후 TSLP conjugate를 100 ㎕씩 넣고 2시간 동안 상온에서 반응시켰다. 다시 5회 세척 후 substrate solution을 100 ㎕씩 넣어 30분 동안 상온에서 빛을 차단한 채 반응시켰다. 마지막으로 stop solution 100 ㎕를 넣고 450 ㎚에서 흡광도를 측정하였다.In order to measure the amount of TSLP produced in serum and BALF, 50 µl of the serum, supernatant and standard separated as described above were dispensed into each well, 50 µl of RD1-21 reagent was added and mixed, and then reacted at room temperature for 2 hours. After washing 5 times using a washing buffer, 100 µl of TSLP conjugate was added and reacted at room temperature for 2 hours. After washing again 5 times, 100 µl of the substrate solution was added and reacted at room temperature for 30 minutes while blocking the light. Finally, 100 µl of the stop solution was added and the absorbance was measured at 450 nm.
혈청 및 BALF 내 LTB4 생성량을 측정하기 위하여, 상기와 같이 분리한 혈청, 상등액과 standard를 50 ㎕씩 넣고 추가로 primary antibody solution 50 ㎕를 넣어 1시간 동안 상온에서 plate shaker를 이용하여 혼합하였다. 이후, LTB4 conjugate 50 ㎕를 넣고 다시 3시간 동안 상온에서 plate shaker를 이용하여 혼합하였다. 그 다음 washing buffer를 이용해 2회 세척한 후 substrate solution 200 ㎕를 첨가하고 상온에서 30분 동안 빛을 차단한 채 반응시켰다. 마지막으로 stop solution 100 ㎕를 넣고 450 ㎚에서 흡광도를 측정하였다.In order to measure the amount of LTB4 produced in serum and BALF, 50 µl of serum, supernatant and standard separated as described above were added each, and 50 µl of primary antibody solution was added thereto, followed by mixing using a plate shaker at room temperature for 1 hour. Thereafter, 50 µl of LTB 4 conjugate was added and mixed again for 3 hours at room temperature using a plate shaker. Then, after washing twice with a washing buffer, 200 µl of the substrate solution was added and reacted at room temperature for 30 minutes while blocking the light. Finally, 100 µl of the stop solution was added and the absorbance was measured at 450 nm.
상기 실험의 결과는 SPSS Ver. 18.0의 unpaired student's T-test와 ANOVA를 사용하여 통계처리 하였고 p<0.05, p<0.01 및 p<0.001 수준에서 그 유의성을 검정하였다.The results of the above experiment are SPSS Ver. Statistical processing was performed using an unpaired student's T-test and ANOVA of 18.0, and the significance was tested at the levels p<0.05, p<0.01, and p<0.001.
그 결과, 하기 표 2에 나타낸 바와 같이, 혈액 내 면역세포 수 분석을 통해 국화 및 황금 혼합 추출물을 투여한 알레르기성 천식 마우스 모델에서 천식으로 인한 기도 염증에 대항하는 백혈구, 호염기구, 림프구, 단핵구의 수가 대조군에 비하여 유의적으로 증가하고, 천식으로 인하여 증가하는 호산구 및 호중구 수가 대조군에 비하여 유의적으로 감소하는 것을 확인하였다. 또한, BALF 내 총 면역세포 수 분석을 통해 국화 및 황금 혼합 추출물을 투여한 천식 마우스 모델에서 천식으로 인해 증가하는 염증세포 수가 대조군에 비하여 유의적으로 감소하는 것을 확인하였다(표 2).As a result, as shown in Table 2 below, leukocytes, basophils, lymphocytes, and monocytes against airway inflammation due to asthma in an allergic asthma mouse model administered with a mixture of chrysanthemum and golden extracts through the analysis of the number of immune cells in the blood It was confirmed that the number was significantly increased compared to the control group, and the number of eosinophils and neutrophils increased due to asthma was significantly decreased compared to the control group. In addition, through the analysis of the total number of immune cells in BALF, it was confirmed that the number of inflammatory cells increased due to asthma was significantly decreased in the asthma mouse model administered with the mixed extract of chrysanthemum and gold compared to the control group (Table 2).
또한, 하기 표 3에 나타낸 바와 같이, 혈청 및 BALF 내 난알부민-특이 IgE, 히스타민, TGF-β1, TSLP 및 LTB4 생성량 분석을 통해 국화 및 황금 혼합 추출물을 투여한 알레르기성 천식 마우스 모델에서 천식으로 인한 염증을 통해 증가하는 IgE, 히스타민, TGF-β1, TSLP, LTB4 생성량이 대조군에 비하여 유의적으로 감소하는 것을 확인하였다(표 3).In addition, as shown in Table 3 below, in serum and BALF in oalbumin-specific IgE, histamine, TGF-β1, TSLP and LTB 4 production amount analysis through the administration of a mixture of chrysanthemum and golden extracts from allergic asthma mouse model to asthma It was confirmed that the production amount of IgE, histamine, TGF-β1, TSLP, and LTB 4 increased through inflammation caused by inflammation significantly decreased compared to the control group (Table 3).
또한, 하기 표 4에 나타낸 바와 같이, 혈청 및 BALF 내 사이토카인 생성량 분석을 통해 국화 및 황금 혼합 추출물을 투여한 알레르기성 천식 마우스 모델에서 천식으로 인한 염증에 의해 증가하는 IL-1β, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-17E, IL-33, TNF-α 생성량이 대조군에 비하여 유의적으로 감소하고, Th2 반응이 우세하게 나타나는 천식으로 인해 감소하는 IL-2, IL-12, IFN-γ 생성량이 대조군에 비하여 유의적으로 증가하는 것을 확인하였다(포 4).In addition, as shown in Table 4 below, IL-1β, IL-4, which are increased by inflammation due to asthma in an allergic asthma mouse model administered with a mixture of chrysanthemum and golden extracts through analysis of cytokine production in serum and BALF, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-17E, IL-33, TNF-α production significantly decreased compared to the control group, It was confirmed that the production of IL-2, IL-12, and IFN-γ, which decreased due to asthma, where Th2 response was predominant, increased significantly compared to the control group (Po 4).
상기의 결과를 통해 국화 및 황금 혼합 추출물이 염증 및 기관지 수축 완화와 면역 불균형 상태 회복을 통해 천식에 대한 개선 효과가 있음을 확인하였다. 또한, 국화 및 황금 혼합 추출물의 혼합 비율이 7 : 3인 경우 천신 개선 효과가 보다 우수함을 확인하였다.
Through the above results, it was confirmed that the mixed extract of chrysanthemum and gold has an improvement effect on asthma through relieving inflammation and bronchial contraction and recovering an immune imbalance. In addition, when the mixing ratio of the mixed extract of chrysanthemum and golden gold was 7:3, it was confirmed that the effect of improving cheonshin is more excellent.
<< 실험예Experimental example 4> 미세먼지 유도 마우스 모델에서 국화 및 황금 혼합 추출물의 4> Induction of fine dust in mouse model of mixed extract of chrysanthemum and gold 항미세먼지Anti-fine dust 효과 확인 Check the effect
<4-1> 미세먼지 유도 마우스 모델 제작 및 국화 및 황금 혼합 추출물 투여<4-1> Fine dust-inducing mouse model production and administration of mixed extract of chrysanthemum and gold
실험동물인 수컷 5주령의 BALB/c 수컷 생쥐(20∼22 g)를 ㈜샘타코에서 공급받아 실험 당일까지 충분한 고형사료(Envigo, U.K.)와 물을 공급하고 온도 22 ± 2℃, 습도 55 ± 15%, 12시간-12시간(light-dark cycle)의 환경에서 2주간 적응시킨 뒤 실험에 사용하였다. 본 실험은 대전대학교 동물실험윤리 위원회로부터 승인(동물사용 윤리위원회 승인번호.DJUARB2017-017)을 받아 동물윤리준칙에 의거해서 실험하였다.An experimental animal, male 5-week-old BALB/c male mice (20∼22 g), was supplied from Samtaco Co., Ltd. and supplied with sufficient solid feed (Envigo, UK) and water until the day of the experiment, and a temperature of 22 ± 2℃ and a humidity of 55 ± It was used in the experiment after acclimating for 2 weeks in an environment of 15%, 12 hours-12 hours (light-dark cycle). This experiment was approved by the Animal Experimental Ethics Committee of Daejeon University (approval number of the Animal Use Ethics Committee, DJUARB2017-017) and was conducted in accordance with the Animal Ethics Code.
미세먼지 유도 마우스 모델을 제작하기 위해 먼저, coal fly ash와 diesel particulate matter를 각각 5 ㎎/㎖ 농도로 DMSO에 용해시키고 최종농도가 coal fly ash는 0.5 ㎎/㎖, diesel particulate matter는 0.75 ㎎/㎖가 되도록 PBS로 희석한 후 수산화알루미늄 겔 [Al(OH)3 gel]이 8%가 되게 첨가하여 미세먼지 혼합물을 제조하였다. 미세먼지 혼합물의 투여는 시료 투여 시작 후 3일 후, 6일 후에 총 2회로 INT(Intra-Nasal-Trachea) 방법을 이용하여 미세먼지 혼합물을 주입하였다. 에테르를 이용하여 실험동물을 마취시키고 고무줄로 고정하여 기도를 확보한 후에 구강을 통해 기도로 미세먼지 혼합물을 50 ㎕ 주입하며, 동시에 코에도 미세먼지 혼합물을 50 ㎕를 함께 넣어주어 생쥐가 숨을 쉬는 과정에서 기관지를 통해 폐로 미세먼지 혼합물이 흡입될 수 있도록 유도하였다. 실험군은 아무것도 처리하지 않는 정상군과 미세먼지 유도 마우스에게 증류수를 경구 투여하는 대조군, 미세먼지 유도 마우스에게 상기 <실시예 3>의 국화 및 황금 혼합 추출물로서 6:4, 7:3, 8:2 비율로 혼합한 시료를 50, 100, 200 ㎎/㎏으로 경구투여하는 실험군 등 총 11개 그룹으로 나누어 7일간 경구 투여를 진행하였다.
To make a mouse model inducing fine dust, first, coal fly ash and diesel particulate matter were dissolved in DMSO at a concentration of 5 mg/ml, respectively, and the final concentration was 0.5 mg/ml for coal fly ash and 0.75 mg/ml for diesel particulate matter. After dilution with PBS so as to be, aluminum hydroxide gel [Al(OH) 3 gel] was added so as to be 8% to prepare a fine dust mixture. In the administration of the fine dust mixture, the fine dust mixture was injected using the INT (Intra-Nasal-Trachea) method twice in total, 3 days after the start of the sample administration, and 6 days after the sample administration. After anesthetizing the experimental animal with ether and securing the airway by fixing it with a rubber band, 50 µl of the fine dust mixture is injected into the airway through the oral cavity. At the same time, 50 µl of the fine dust mixture is also added to the nose so that the mice breathe. In the process, the fine dust mixture was induced to be inhaled into the lungs through the bronchi. The experimental group was a control group in which distilled water was orally administered to the normal group and fine dust-inducing mice that were not treated with anything, and the chrysanthemum and golden mixed extracts of the above <Example 3> were 6:4, 7:3, 8:2. The samples mixed at the ratio were divided into 11 groups, including the experimental group, which was administered orally at 50, 100, and 200 mg/kg, and oral administration was performed for 7 days.
<4-2> 국화 및 황금 혼합 추출물의 <4-2> Chrysanthemum and golden mixed extract 항미세먼지Anti-fine dust 효과 확인 Check the effect
국화 및 황금 혼합 추출물의 항미세먼지 효과를 확인하기 위하여, 미세먼지 유도 마우스 모델에 국화 및 황금 혼합 추출물을 투여한 후, 점액 분비량, 혈청 내 LTB4 LTC4, LTD4 생성량을 측정하였다.In order to confirm the anti-fine dust effect of the mixed extract of chrysanthemum and gold, after administering the mixed extract of chrysanthemum and gold to a mouse model inducing fine dust, the amount of mucus secretion and the amount of LTB 4 LTC 4 , LTD 4 produced in the serum were measured.
구체적으로, 상기 실험예 <4-1>에 기재된 방법과 동일한 방법으로 미세먼지 유도 마우스 모델을 제작하고, 국화 및 황금 혼합 추출물을 투여하여 실험을 진행하였다.Specifically, a microdust-inducing mouse model was prepared by the same method as described in Experimental Example <4-1>, and an experiment was conducted by administering a mixed extract of chrysanthemum and gold.
점액분비량을 측정하기 위하여, 실험 종료 30분 전에 페놀레드(phenol red) 10 ㎎/㎏를 200 ㎕씩 실험동물 복강에 주사하였다. 이 후, 에틸에테르로 마취한 상태에서 심장 천자법으로 채혈한 다음 기관 (trachea) 전체를 절제하였다. 분리된 기관을 1㎖의 생리식염수에 넣어 30분 간 조직을 vortexing한 후, 5분간 10,000 rpm에서 원심분리 하였으며, 분리한 상층액 900 ㎕와 1M NaOH 100 ㎕를 넣어 발색시키고 546 ㎚에서 흡광도를 측정하였다. 이를 적출한 기도의 무게로 나누어 기도에 대한 페놀레드의 비율을 구하여 기도에서의 점액분비량을 구하였다.In order to measure the amount of mucus secretion, 200 µl of phenol red was injected into the peritoneal cavity of the
혈청 내 LTB4 생성량을 측정하기 위하여, 실험 종료 후 에틸에테르로 마취한 상태에서 심장 천자법으로 채혈한 다음 혈액을 15분간 3,000 rpm에서 원심 분리해서 혈청을 분리하였고 이 후, 분리한 혈청과 standard를 50 ㎕씩 넣고 추가로 primary antibody solution 50 ㎕를 넣어 1시간 동안 상온에서 plate shaker를 이용하여 혼합하였다. 이후, LTB4 conjugate 50 ㎕를 넣고 다시 3시간 동안 상온에서 plate shaker를 이용하여 혼합하였다. 그 다음 washing buffer를 이용해 2회 세척한 후 substrate solution 200 ㎕를 첨가하고 상온에서 30분 동안 빛을 차단한 채 반응시켰다. 마지막으로 stop solution 100 ㎕를 넣고 450 ㎚에서 흡광도를 측정하였다.To measure the amount of LTB 4 produced in the serum, after the experiment was completed, blood was collected by cardiac puncture under anesthesia with ethyl ether, and then the blood was centrifuged at 3,000 rpm for 15 minutes to separate the serum. After that, the separated serum and standard were separated. 50 µl each, and 50 µl of the primary antibody solution were added thereto, followed by mixing using a plate shaker at room temperature for 1 hour. Thereafter, 50 µl of LTB4 conjugate was added and mixed again for 3 hours at room temperature using a plate shaker. Then, after washing twice with a washing buffer, 200 µl of the substrate solution was added and reacted at room temperature for 30 minutes while blocking the light. Finally, 100 µl of the stop solution was added and the absorbance was measured at 450 nm.
혈청 내 LTC4 및 LTD4 생성량을 측정하기 위하여, 실험 종료 후 에틸에테르로 마취한 상태에서 심장 천자법으로 채혈한 다음 혈액을 15분간 3,000 rpm에서 원심 분리해서 혈청을 분리하였고 이 후, 분리한 혈청과 standard를 100 ㎕씩 각 웰에 분주하고 10 ㎕의 balance solution과 50 ㎕의 conjugate를 넣어 1시간 동안 37℃에서 반응시켰다. washing buffer를 이용하여 5회 세척 후 substrate A와 B를 각각 50 ㎕씩 넣어 15분 동안 37℃에서 반응시키고 50 ㎕의 stop solution을 추가하여 450 ㎚에서 흡광도를 측정하였다.In order to measure the amount of LTC 4 and LTD 4 produced in the serum, blood was collected by cardiac puncture under anesthesia with ethyl ether after the end of the experiment, and then the blood was centrifuged at 3,000 rpm for 15 minutes to separate the serum. 100 µl of standard and 100 µl were dispensed into each well, and 10 µl of balance solution and 50 µl of conjugate were added and reacted at 37°C for 1 hour. After washing 5 times using a washing buffer, 50 µl each of substrates A and B were added to react at 37°C for 15 minutes, and 50 µl of stop solution was added to measure absorbance at 450 nm.
또한, 상기 실험의 결과는 SPSS Ver. 18.0의 unpaired student's T-test와 ANOVA를 사용하여 통계처리 하였고 p<0.05, p<0.01 및 p<0.001 수준에서 그 유의성을 검정하였다.In addition, the result of the above experiment is SPSS Ver. Statistical processing was performed using an unpaired student's T-test and ANOVA of 18.0, and the significance was tested at the levels p<0.05, p<0.01, and p<0.001.
그 결과, 하기 표 5에 나타낸 바와 같이, 국화 및 황금 혼합 추출물을 투여한 미세먼지 유도 마우스 모델에서 기관지 내 점액 분비량이 대조군에 비해 유의적으로 증가하는 것을 확인하였다. 이는 국화 및 황금 혼합 추출물이 점액의 분비를 촉진시켜 그 양을 증가시키고, 점액 혹은 담의 점성을 낮추어 섬모운동의 촉진함으로써 기관지 속으로 유입된 이물질의 배설을 용이하게 함을 의미한다(표 5). As a result, as shown in Table 5 below, it was confirmed that the amount of mucus secretion in the bronchi was significantly increased compared to the control group in the microdust-inducing mouse model administered with the mixed extract of chrysanthemum and gold. This means that the mixed extract of chrysanthemum and gold promotes the secretion of mucus, increasing its amount, and lowering the viscosity of mucus or biliary tract to promote ciliary movement, thereby facilitating the excretion of foreign substances introduced into the bronchi (Table 5). .
또한, 국화 및 황금 혼합 추출물을 투여한 미세먼지 유도 마우스 모델에서 혈청 내 LTC4 및 LTD4 생성량이 대조군에 비해 유의적으로 감소하는 것을 확인하였다. 이는 국화 및 황금 혼합 추출물이 기관지 질환이나 염증의 중요한 역할을 하는 류코트리엔(leukotriene)의 생성을 억제하여 기관지 질환을 개선함을 의미한다(표 5). In addition, it was confirmed that the amount of LTC 4 and LTD 4 production in serum was significantly reduced compared to the control group in a microdust-inducing mouse model administered with a mixed extract of chrysanthemum and gold. This means that the mixed extract of chrysanthemum and gold suppresses the production of leukotriene, which plays an important role in bronchial disease or inflammation, thereby improving bronchial disease (Table 5).
상기의 결과를 통해 국화 및 황금 혼합 추출물이 거담 배출능을 증가시키고, 류코트리엔 생성량을 감소시켜 미세먼지에 의한 호흡기 질환 개선 효과가 있음을 확인하였다. 또한, 국화 및 황금 혼합 추출물의 혼합 비율이 7 : 3인 경우 미세먼지에 의한 호흡기 질환 개선 효과가 보다 우수함을 확인하였다.
Through the above results, it was confirmed that the mixed extract of chrysanthemum and gold has an effect of improving the respiratory tract disease due to fine dust by increasing the expulsion ability of expectorant and reducing the amount of leukotriene produced. In addition, when the mixing ratio of the mixed extract of chrysanthemum and gold was 7:3, it was confirmed that the effect of improving respiratory diseases due to fine dust was more excellent.
상기 <실험예 1> 내지 <실험예 4>의 결과를 통해 본 발명의 국화 및 황금 혼합 추출물은 세포독성이 없고, 유의적인 항염증 효과를 나타내며, 기관지 세포에서 염증성 점액단백질의 분비를 유의적으로 억제하고, 천식 및 미세먼지에 의한 호흡기 질환 개선 효과가 있음을 확인하였다. 또한, 보다 우수한 효과를 나타내는 국화 및 황금 혼합 추출물의 최적 혼합 비율은 6:4 내지 7:3임을 확인하였다.According to the results of <Experimental Example 1> to <Experimental Example 4>, the mixed extract of chrysanthemum and gold of the present invention has no cytotoxicity, exhibits a significant anti-inflammatory effect, and significantly inhibits the secretion of inflammatory mucoproteins from bronchial cells. It was confirmed that there is an effect of suppressing and improving respiratory diseases due to asthma and fine dust. In addition, it was confirmed that the optimal mixing ratio of the mixed extract of chrysanthemum and gold showing a more excellent effect was 6:4 to 7:3.
따라서, 본 발명의 최적 혼합 비율로 혼합된 국화 및 황금 혼합 추출물을 기관지염, 천식, 폐렴, 만성 폐쇄성 폐질환 등을 포함하는 호흡기 질환 예방 또는 치료용, 진해 또는 거담용 조성물의 유효성분으로 이용할 수 있다.
Therefore, the mixed extract of chrysanthemum and gold mixed in the optimal mixing ratio of the present invention can be used as an active ingredient of a composition for preventing or treating respiratory diseases including bronchitis, asthma, pneumonia, chronic obstructive pulmonary disease, etc. .
하기에 본 발명의 조성물을 위한 제조예를 예시한다.
Hereinafter, examples of preparation for the composition of the present invention are illustrated.
<< 제조예Manufacturing example 1> 약학적 제제의 제조 1> Preparation of pharmaceutical formulation
<1-1> <1-1> 산제의Powdery 제조 Produce
본 발명의 혼합 추출물 10 mg10 mg of mixed extract of the present invention
유당 1 g1 g lactose
상기의 성분을 혼합하고 기밀포에 충진하여 산제를 제조하였다.
The above ingredients were mixed and filled in an airtight cloth to prepare a powder.
<1-2> 정제의 제조<1-2> Preparation of tablets
본 발명의 혼합 추출물 0.1 mg0.1 mg of mixed extract of the present invention
옥수수전분 100 mg100 mg corn starch
유 당 100 mg100 mg lactose
스테아린산 마그네슘 2 mg2 mg of magnesium stearate
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.
After mixing the above ingredients, tablets were prepared by tableting according to a conventional tablet preparation method.
<1-3> 캡슐제의 제조<1-3> Preparation of capsules
본 발명의 혼합 추출물 0.1 mg0.1 mg of mixed extract of the present invention
옥수수전분 100 mg100 mg corn starch
유 당 100 mg100 mg lactose
스테아린산 마그네슘 2 mg2 mg of magnesium stearate
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.
After mixing the above ingredients, a gelatin capsule was filled according to a conventional capsule preparation method to prepare a capsule formulation.
<1-4> 환의 제조<1-4> Preparation of ring
본 발명의 혼합 추출물 1 mg1 mg of mixed extract of the present invention
유당 1.5 g1.5 g lactose
글리세린 1 g1 g glycerin
자일리톨 0.5 g0.5 g xylitol
상기의 성분을 혼합한 후, 통상의 방법에 따라 1 환 당 4 g이 되도록 제조하였다.
After mixing the above components, it was prepared so as to be 4 g per pill according to a conventional method.
<1-5> 과립의 제조<1-5> Preparation of granules
본 발명의 혼합 추출물 0.15 mg0.15 mg of mixed extract of the present invention
대두 추출물 50 mg50 mg soybean extract
포도당 200 mg200 mg glucose
전분 600 mg600 mg starch
상기의 성분을 혼합한 후, 30% 에탄올 100 mg을 첨가하여 60℃에서 건조하여 과립을 형성한 후 포에 충진하였다.
After mixing the above ingredients, 100 mg of 30% ethanol was added and dried at 60° C. to form granules, and then filled into a cloth.
<< 제조예Manufacturing example 2> 건강식품의 제조 2> Manufacture of health food
본 발명의 혼합 추출물을 유효성분으로 함유하는 식품들을 다음과 같이 제조하였다.
Foods containing the mixed extract of the present invention as an active ingredient were prepared as follows.
<2-1> 밀가루 식품의 제조<2-1> Preparation of flour food
본 발명의 혼합 추출물의 0.5 내지 5.0 중량부를 밀가루에 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하였다.
0.5 to 5.0 parts by weight of the mixed extract of the present invention was added to flour, and bread, cakes, cookies, crackers and noodles were prepared using this mixture.
<2-2> <2-2> 스프soup 및 육즙(gravies)의 제조 And the production of gravies
본 발명의 혼합 추출물의 0.1 내지 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 mixed extract of the present invention was added to soups and broth to prepare health-promoting meat products, noodles soup, and broth.
<2-3> 그라운드 <2-3> Ground 비프(ground beef)의Of ground beef 제조 Produce
본 발명의 혼합 추출물의 10 중량부를 그라운드 비프에 첨가하여 건강 증진용 그라운드 비프를 제조하였다.
Ground beef for health promotion was prepared by adding 10 parts by weight of the mixed extract of the present invention to ground beef.
<2-4> 유제품(dairy products)의 제조<2-4> Manufacture of dairy products
본 발명의 혼합 추출물의 5 내지 10 중량부를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.
5 to 10 parts by weight of the mixed extract of the present invention was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.
<2-5> <2-5> 선식의Linear 제조 Produce
현미, 보리, 찹쌀, 율무를 공지의 방법으로 알파화시켜 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.Brown rice, barley, glutinous rice, and adlay were gelatinized and dried by a known method, and then roasted, and then prepared into a powder having a particle size of 60 mesh with a grinder.
검정콩, 검정깨, 들깨도 공지의 방법으로 쪄서 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.Black beans, black sesame seeds, and perilla seeds were also steamed and dried by a known method, and then roasted, and then prepared into a powder having a particle size of 60 mesh with a grinder.
본 발명의 혼합 추출물을 진공 농축기에서 감압농축하고, 분무, 열풍건조기로 건조하여 얻은 건조물을 분쇄기로 입도 60 메쉬로 분쇄하여 건조분말을 얻었다.The mixed extract of the present invention was concentrated under reduced pressure in a vacuum concentrator, sprayed and dried with a hot air dryer, and the resulting dried product was pulverized with a grinder to a particle size of 60 mesh to obtain a dry powder.
상기에서 제조한 곡물류, 종실류 및 본 발명의 혼합 추출물을 다음의 비율로 배합하여 제조하였다.It was prepared by blending the grains, seeds and the mixed extract of the present invention prepared above in the following ratio.
곡물류(현미 30 중량부, 율무 15 중량부, 보리 20 중량부),Grains (30 parts by weight of brown rice, 15 parts by weight of barley, 20 parts by weight of barley),
종실류(들깨 7 중량부, 검정콩 8 중량부, 검정깨 7 중량부),Seeds (perilla 7 parts by weight,
본 발명의 혼합 추출물(3 중량부),The mixed extract of the present invention (3 parts by weight),
영지(0.5 중량부),Ganoderma lucidum (0.5 parts by weight),
지황(0.5 중량부)
Rehmannia (0.5 parts by weight)
<< 제조예Manufacturing example 3> 3> 건강음료의Health drink 제조 Produce
<3-1> <3-1> 건강음료의Health drink 제조 Produce
액상과당(0.5%), 올리고당(2%), 설탕(2%), 식염(0.5%), 물(75%)과 같은 부재료와 본 발명의 혼합 추출물 0.5 g을 균질하게 배합하여 순간 살균을 한 후 이를 유리병, 패트병 등 소포장 용기에 포장하여 제조하였다.
Subsidiary materials such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%), water (75%) and 0.5 g of the mixed extract of the present invention are homogeneously mixed to perform instant sterilization. After this, it was prepared by packaging it in a small container such as a glass bottle or a plastic bottle.
<3-2> 야채 주스의 제조<3-2> Preparation of vegetable juice
본 발명의 혼합 추출물 0.5 g을 토마토 또는 당근 주스 1,000 ㎖에 가하여 야채 주스를 제조하였다.
Vegetable juice was prepared by adding 0.5 g of the mixed extract of the present invention to 1,000 ml of tomato or carrot juice.
<3-3> 과일 주스의 제조<3-3> Preparation of fruit juice
본 발명의 혼합 추출물 0.1 g을 사과 또는 포도 주스 1,000 ㎖에 가하여 과일 주스를 제조하였다.Fruit juice was prepared by adding 0.1 g of the mixed extract of the present invention to 1,000 ml of apple or grape juice.
Claims (11)
상기 국화 추출물 : 황금 추출물을 5 : 5 내지 8 : 2의 중량비로 함유하고,
여기에서 국화 추출물은 물, C1 내지 C2의 저급 알코올 또는 이들의 혼합용매로 추출한 것이고, 황금 추출물은 물로 추출한 것인,
호흡기 질환 예방 또는 치료용 약학적 조성물로서,
상기 호흡기 질환은 천식, 기관지염, 폐렴, 기침 또는 가래를 동반하는 폐기종, 기관지 확장증, 폐섬유증 및 만성폐쇄성 폐질환(chronic obstructive pulmonary disease)으로 이루어진 군으로부터 선택되는 어느 하나 이상의 질환인 조성물.
It contains chrysanthemum ( Chrysanthemum morifolium Ramatuelle ) extract and golden ( Scutellaria baicalensis ) extract as active ingredients,
The chrysanthemum extract: contains a golden extract in a weight ratio of 5: 5 to 8: 2,
Here, the chrysanthemum extract is extracted with water, a lower alcohol of C 1 to C 2 or a mixed solvent thereof, and the golden extract is extracted with water,
As a pharmaceutical composition for preventing or treating respiratory diseases,
The respiratory disease is any one or more diseases selected from the group consisting of asthma, bronchitis, pneumonia, emphysema accompanied by cough or sputum, bronchiectasis, pulmonary fibrosis, and chronic obstructive pulmonary disease.
According to claim 1, wherein the chrysanthemum extract: containing the golden extract in a weight ratio of 5.5: 4.5 to 7.5: 2.5, a pharmaceutical composition for preventing or treating respiratory diseases.
The pharmaceutical composition for preventing or treating respiratory diseases according to claim 2, which contains the chrysanthemum extract: golden extract in a weight ratio of 6:4 to 7:3.
The pharmaceutical composition for preventing or treating respiratory diseases according to claim 1, wherein the extract inhibits secretion of inflammatory mucous proteins.
The pharmaceutical composition for preventing or treating respiratory diseases according to claim 7, wherein the inflammatory mucoprotein is Mucin 5AC (MUC5AC).
여기에서 국화 추출물은 물, C1 내지 C2의 저급 알코올 또는 이들의 혼합용매로 추출한 것이고, 황금 추출물은 물로 추출한 것인,
호흡기 질환 예방 또는 개선용 건강식품으로서,
상기 호흡기 질환은 천식, 기관지염, 폐렴, 기침 또는 가래를 동반하는 폐기종, 기관지 확장증, 폐섬유증 및 만성폐쇄성 폐질환(chronic obstructive pulmonary disease)으로 이루어진 군으로부터 선택되는 어느 하나 이상의 질환인 건강식품.
It contains chrysanthemum extract and golden extract as active ingredients, and contains the chrysanthemum extract: golden extract in a weight ratio of 5:5 to 8:2,
Here, the chrysanthemum extract is extracted with water, a lower alcohol of C 1 to C 2 or a mixed solvent thereof, and the golden extract is extracted with water,
As a health food for preventing or improving respiratory diseases,
The respiratory disease is any one or more diseases selected from the group consisting of asthma, bronchitis, pneumonia, emphysema accompanied by cough or sputum, bronchiectasis, pulmonary fibrosis, and chronic obstructive pulmonary disease.
여기에서 국화 추출물은 물, C1 내지 C2의 저급 알코올 또는 이들의 혼합용매로 추출한 것이고, 황금 추출물은 물로 추출한 것인,
진해 또는 거담용 약학적 조성물.
It contains chrysanthemum extract and golden extract as active ingredients, and contains the chrysanthemum extract: golden extract in a weight ratio of 5:5 to 8:2,
Here, the chrysanthemum extract is extracted with water, a lower alcohol of C 1 to C 2 or a mixed solvent thereof, and the golden extract is extracted with water,
Pharmaceutical composition for antitussive or expectorant.
여기에서 국화 추출물은 물, C1 내지 C2의 저급 알코올 또는 이들의 혼합용매로 추출한 것이고, 황금 추출물은 물로 추출한 것인,
진해 또는 거담용 건강식품.It contains chrysanthemum extract and golden extract as active ingredients, and contains the chrysanthemum extract: golden extract in a weight ratio of 5:5 to 8:2,
Here, the chrysanthemum extract is extracted with water, a lower alcohol of C 1 to C 2 or a mixed solvent thereof, and the golden extract is extracted with water,
Health food for Jinhae or Geodam.
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| KR1020170135675 | 2017-10-19 | ||
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| KR1020180093338A KR102252126B1 (en) | 2017-10-19 | 2018-08-09 | Composition for prevention or treatment respiratory diseases comprising combination extracts of Chrysanthemum morifolium Ramatuelle and Scutellaria baicalensis as an active ingredient |
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| KR102351651B1 (en) | 2019-11-07 | 2022-01-18 | 주식회사 에치와이 | Composition for Prevention, Improvement or Treatment of Fine Dust Stimulation Respiratory Disease comprising Mixture of Natural Origin |
| KR20220105363A (en) | 2021-01-20 | 2022-07-27 | (주)뷰티나인 | Composition for preventing or improving respiratory disease comprising Chaste tree extract |
| KR20240033710A (en) | 2022-09-02 | 2024-03-13 | (주)에스디생명공학 | Composition for Prevention and Treatment of Cough, Sputum, and Bronchial Disease as an Active Ingredient |
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| KR101567325B1 (en) * | 2013-07-16 | 2015-11-10 | (주)국심 | A functional compositoion comprising Chrysanthemum morifolium extract |
| KR20150047047A (en) * | 2013-10-23 | 2015-05-04 | 동의대학교 산학협력단 | Pharmaceutical composition for preventing or treating inflammatory diseases comprising water extract containing baicalin from Scutellaria baicalensis through immune modulation |
| KR101715274B1 (en) * | 2014-07-03 | 2017-03-13 | 원광대학교산학협력단 | Composition containing extract or fractions of Chrysanthemum indicum L. for treating, improving or preventing inflammatory disease |
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| Anatomy & Cell Biology. 2017. Vol.50. No.2, pp.124-134.* |
| 천궁석고탕. 세의득효방(1345년). 한국전통지식포탈.* |
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