KR20220087653A - Anti-viral composition containing the extract of Geranium thunbergii Siebold et Zuccarini as an active ingredient - Google Patents
Anti-viral composition containing the extract of Geranium thunbergii Siebold et Zuccarini as an active ingredient Download PDFInfo
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- KR20220087653A KR20220087653A KR1020200177680A KR20200177680A KR20220087653A KR 20220087653 A KR20220087653 A KR 20220087653A KR 1020200177680 A KR1020200177680 A KR 1020200177680A KR 20200177680 A KR20200177680 A KR 20200177680A KR 20220087653 A KR20220087653 A KR 20220087653A
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Abstract
본 발명은 현초 추출물을 유효성분으로 포함하는 코로나 바이러스에 대한 항바이러스 용도에 관한 것이다. 구체적으로, 본 발명의 현초 추출물은 사스코로나바이러스-2(SARS-CoV-2)와 같은 코로나바이러스의 감염을 억제하는 효과를 나타내므로, 상기 바이러스 질환을 예방 또는 치료를 위한 항바이러스제 개발에 관한 것이다.The present invention relates to an antiviral use for corona virus comprising an extract of Hyeoncho as an active ingredient. Specifically, the extract of the present invention relates to the development of an antiviral agent for preventing or treating the viral disease, since it exhibits an effect of inhibiting infection of a coronavirus such as SARS-CoV-2 (SARS-CoV-2). .
Description
본 발명은 현초 추출물을 유효성분으로 포함하는 항바이러스 조성물에 관한 것으로, 구체적으로 현초 추출물을 유효성분으로 포함하는 사스 코로나바이러스-2 감염 질환의 예방, 개선 또는 치료용도에 관한 것이다.The present invention relates to an antiviral composition comprising an extract of chrysanthemum as an active ingredient, and more particularly, to a use for preventing, improving or treating SARS-CoV-2 infection comprising the extract as an active ingredient.
코로나 바이러스(coronavirus)는 1937년 닭에서 처음 발견된 뒤 개, 돼지, 조류 등의 동물을 거쳐 1965년에는 사람에게서도 발견되었다. 개기일식 때 태양의 광구가 달에 가려졌을 때 그 둘레에서 하얗게 빛나는 현상인 코로나 현상과 생김새가 비슷하여 이러한 이름이 붙여졌다.Coronavirus was first discovered in chickens in 1937, followed by animals such as dogs, pigs, and birds, and then in humans in 1965. During a total solar eclipse, when the sun's photosphere is obscured by the moon, it is given this name because its appearance is similar to the corona phenomenon, which is a phenomenon that glows white around the moon.
코로나바이러스는 사람과 동물에서 주로 폐렴과 장염을 유발하는 것으로 알려져 있으며, 간혹 신경계 감염과 간염을 유발하는 것으로도 알려져 있다. 코로나바이러스는 코로나바이러스과(Coronaviridae)에 속하며 구형의 외막을 가지는, 약 100-120 nm 크기의 positive sense RNA 바이러스이다(Master, 2006). 코로나바이러스는 가장 외각에 있는 스파이크(spike) 단백질 (S), hemagglutinin-esterase (HE) 단백질, transmembrane (M) 단백질, small membrane (E) 단백질 및 nucleocapsid (N) 단백질 등 총 5개의 구조 단백질로 이루어져 있다(Lai and Homes, 2001. Fields Virology). 이 중 스파이크(spike) 단백질은 세포 수용체(ACE2)와 결합하는 리간드 역할을 하며, 숙주세포와 바이러스간의 융합을 유도하는 단백질로 가장 변이가 심한 단백질로 알려져 있다.Coronaviruses are known to mainly cause pneumonia and enteritis in humans and animals, and are also known to occasionally cause nervous system infections and hepatitis. Coronavirus belongs to the coronaviridae and is a positive sense RNA virus with a spherical outer membrane and a size of about 100-120 nm (Master, 2006). Coronavirus consists of a total of five structural proteins: the outermost spike protein (S), hemagglutinin-esterase (HE) protein, transmembrane (M) protein, small membrane (E) protein, and nucleocapsid (N) protein. There is (Lai and Homes, 2001. Fields Virology). Among them, the spike protein acts as a ligand that binds to the cell receptor (ACE2) and induces fusion between the host cell and the virus, and is known as the most mutated protein.
지금까지 코로나바이러스는 사람에게는 거의 감염되지 않고 주로 개, 돼지, 소 등의 동물에 감염되는 병원균으로 인식되어 왔다. 사람에게 감염될 때에도 호흡기 증상을 유발하는 여러 바이러스 가운데 하나로서 단순한 감기를 유발하거나 어린이에게 위험성이 그리 높지 않은 설사 등의 장 질환을 일으키는 경우가 있을 뿐이었다. 그러나 세계적으로 수백명이 넘는 사망자와 수천여 명의 환자를 발생시킨 중증 급성 호흡기 증후군(사스;SARS)의 원인균 및 중동 호흡기 증후군(메르스;MERS)의 원인균이 신종(변종) 코로나바이러스인 것으로 알려지면서 점차적으로 주목받기 시작하였다.So far, coronavirus has been recognized as a pathogen that rarely infects humans and mainly infects animals such as dogs, pigs, and cattle. It is one of several viruses that cause respiratory symptoms even when infecting humans, and only causes a simple cold or intestinal disease such as diarrhea, which is not very dangerous for children. However, as the causative agent of severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS), which caused more than hundreds of deaths and thousands of patients worldwide, are known to be novel (variant) coronaviruses, gradually began to attract attention.
사스는 2002년 11월 중국 남부 광둥(廣東)성에서 발생, 홍콩을 거쳐 세계로 확산된 전염병으로, 갑작스런 발열, 기침 및 호흡곤란이 주 증상이며, 심한 경우 폐렴으로 진행돼 죽음에 이를 수도 있는 질환이다. 전파되는 경로는 아직 완전히 밝혀지지 않았지만 대기 중에 떠다니는 고체나 액체의 미세한 입자에 의해 전파되는 것으로 추측하고 있다. 사스는 2003년 7월까지 유행하였으며, 약 7개월 동안 32개국에서 총 8,096명의 감염자가 발생하고 그 가운데 774명이 사망한 것으로 알려져 있다.SARS is an infectious disease that originated in Guangdong Province in southern China in November 2002 and spread to the world through Hong Kong. to be. The path of propagation is not yet fully elucidated, but it is speculated that it is propagated by fine particles of solid or liquid floating in the atmosphere. The SARS epidemic lasted until July 2003, and in about 7 months, a total of 8,096 infections were reported in 32 countries, and 774 of them were known to have died.
메르스는 2012년 사우디아라비아에서 처음 발견되었고, 고열, 기침 및 호흡곤란 등 심한 호흡기 증상을 나타내며, 심한 경우 합병증이 동반되면서 사망에 이르기도 하는 질환이다. 명확한 감염원과 감염경로는 확인되지 않았으나, 중동 지역의 낙타와의 접촉을 통해 감염될 가능성이 크고 사람 간 밀접접촉에 의한 전파가 가능하다고 보고되었다. 주로 중동 지역에서 환자가 집중적으로 발생하였다가 2015년 5월부터 우리나라 전역에서 100명이 넘는 감염자가 발생한 바 있다.MERS was first discovered in Saudi Arabia in 2012, and it presents severe respiratory symptoms such as high fever, cough and shortness of breath. In severe cases, it is accompanied by complications and even death. Although the clear source and route of infection have not been confirmed, it has been reported that infection is highly likely to be transmitted through contact with camels in the Middle East and transmission is possible through close person-to-person contact. The cases were mainly concentrated in the Middle East, but since May 2015, more than 100 cases have been reported across Korea.
다른 인간 병원체로서 인간코로나바이러스는 일반적인 감기(common cold)를 유발하는 것으로 알려져 있다. 이중 인간코로나바이러스-OC43은 가장 보편적인 인간코로나바이러스로서, 상기도감염(upper respiratory tract infection)을 유발하는 것으로 알려져 있으며, 최근의 연구에 따르면, 다수의 어린이가 2세 이전이 초기에 인간코로나바이러스로 혈청변환(seroconvert)하며, 인간코로나바이러스-OC43이 가장 보편적인 것으로 나타났다. 인간코로나바이러스-OC43 감염은 어린이 또는 노인에서 중증호흡기질환 발병에 관여하는 것으로 나타났으며, 어린이에서 중증호흡기질환을 유발하는 것이 확인되었다(Pediatr. Infect. Dis. J., 32(4):325-329).As another human pathogen, human coronaviruses are known to cause the common cold. Among them, human coronavirus-OC43 is the most common human coronavirus and is known to cause upper respiratory tract infection. It seroconverts, and human coronavirus-OC43 was found to be the most common. Human coronavirus-OC43 infection has been shown to be involved in the development of severe respiratory diseases in children or the elderly, and has been confirmed to cause severe respiratory diseases in children (Pediatr. Infect. Dis. J., 32(4):325). -329).
앞서 언급한대로, 인간코로나바이러스-OC43, 메르스 및 사스는 모두 베타 코로나바이러스(Beta coronavirus) 속에 속하는 변종 코로나바이러스로 알려져 있다. 따라서 인간코로나바이러스-OC43, 메르스-코로나바이러스 및 사스-코로나바이러스는 임상 증상, 병인 및 감염 등에 있어서 유사한 특성을 공유한다. 계통수(phylogenetic tree)에서, 사스-코로나바이러스는 박쥐 사스-유사 코로나바이러스와 다른 박쥐 유래의 코로나바이러스를 포함하는 계통 B에 속하며, 메르스-코로나바이러스는 박쥐 유래의 코로나바이러스를 포함하는 계통 C에 속한다(Trends Microbiol 24:490-502). 나아가, 인간코로나바이러스-OC43은 계통 B 및 계통 C 간의 재조합에 의해 형성되는 계통 D에 속한다.As mentioned earlier, human coronavirus-OC43, MERS and SARS are all known variant coronaviruses belonging to the genus Beta coronavirus. Therefore, human coronavirus-OC43, MERS-coronavirus and SARS-coronavirus share similar characteristics in clinical symptoms, etiology and infection. In the phylogenetic tree, SARS-coronavirus belongs to strain B, which includes bat SARS-like coronaviruses and other bat-derived coronaviruses, and MERS-coronavirus belongs to strain C, which includes bat-derived coronaviruses. (Trends Microbiol 24:490-502). Furthermore, human coronavirus-OC43 belongs to lineage D formed by recombination between lineage B and lineage C.
또 다른 인간바이러스 중 사스코로나바이러스-2(SARS-CoV-2)는 2019년 12월 중국 우한에서 처음 발생한 이후 중국 전역과 전 세계로 확산된, 새로운 유형의 코로나바이러스(SARS-CoV-2)에 의한 호흡기 감염 질환이다. 사스코로나바이러스-2(SARS-CoV-2)는 감염자의 비말(침방울)이 호흡기나 눈, 코, 입의 점막으로 침투될 때 전염된다. 감염되면 약 2 내지 14일의 잠복기를 거친 뒤 발열(37.5도) 및 김침이나 호흡기곤란 등 호흡기 증상, 폐렴이 주증상으로 나타나지만 무증상 감염 사례 빈도도 높게 나오고 있다.Another human virus, SARS-CoV-2, is a new type of coronavirus (SARS-CoV-2) that first emerged in Wuhan, China in December 2019 and has spread throughout China and around the world. It is a respiratory infection caused by SARS-CoV-2 is transmitted when droplets (saliva) of an infected person penetrate the respiratory tract or the mucous membranes of the eyes, nose, and mouth. After an incubation period of about 2 to 14 days, the main symptoms include fever (37.5 degrees), respiratory symptoms such as kimchi or respiratory difficulties, and pneumonia, but the frequency of asymptomatic infections is also high.
현재까지 개발된 항바이러스들은 심한 부작용을 나타내고 있으므로, 그 응용에 있어서 많은 주의가 필요하다. 이러한 치료제는 효과적이지 못하며 부작용 또한 나타나고 있는 실정이다. 그러므로 코로나바이러스의 발생을 예방하고 치료하기 위한 감염 억제 효과가 뛰어나고 독성이 적은 우수한 새로운 코로나 바이러스제의 개발의 필요성이 증가하고 있다.Since the antivirals developed to date show severe side effects, much attention is required in their application. These treatments are not effective and side effects are also present. Therefore, there is an increasing need for the development of excellent novel coronavirus agents with excellent infection suppression effect and low toxicity for preventing and treating coronavirus outbreaks.
또한, RNA 유전자로 이루어진 코로나바이러스의 경우 바이러스 표면의 항원들이 지속적인 변이가 발생하고, 이들 중 어떤 표면 항원이 인체를 감염시킬지 예측이 어렵기 때문에 치료제 개발이 어려운 특징이 있다.In addition, in the case of a coronavirus composed of RNA genes, it is difficult to develop a therapeutic agent because antigens on the surface of the virus are constantly mutated, and it is difficult to predict which surface antigen will infect the human body.
이러한 배경하에, 본 발명자들은 신규한 코로나바이러스 치료제를 개발하기 위한 노력을 계속한 결과, 현초 추출물이 코로나바이러스 증식을 억제하는 우수한 효과가 있음을 확인함으로써, 본 발명을 완성하였다.Under this background, the present inventors have completed the present invention by confirming that as a result of continuing efforts to develop a novel coronavirus therapeutic agent, the Hyeoncho extract has an excellent effect of inhibiting the proliferation of coronavirus.
본 발명의 하나의 목적은 현초 추출물을 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 치료용 약학 조성물을 제공하는 것이다.One object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of a coronavirus infection disease, comprising an extract of Hyeoncho as an active ingredient.
본 발명의 다른 하나의 목적은 현초 추출물을 유효성분으로 포함하는, 코로나바이러스에 대한 항바이러스용 약학 조성물을 제공하는 것이다.Another object of the present invention is to provide a pharmaceutical composition for antiviral against coronavirus, comprising the extract of Hyeoncho as an active ingredient.
본 발명의 또 다른 하나의 목적은 상기 약학 조성물을 인간을 제외한 개체에 투여하는 단계를 포함하는 코로나바이러스 감염 질환의 예방 또는 치료방법을 제공하는 것이다.Another object of the present invention is to provide a method for preventing or treating a coronavirus infection disease comprising administering the pharmaceutical composition to an individual other than a human.
본 발명의 또 다른 하나의 목적은 현초 추출물을 유효성분으로 포함하는 코로나바이러스 감염 질환의 예방 또는 개선용 건강기능식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a health functional food composition for the prevention or improvement of coronavirus-infected diseases comprising an extract of H. ginseng as an active ingredient.
본 발명의 또 다른 하나의 목적은 현초 추출물을 유효성분으로 포함하는 코로나바이러스 감염 질환의 예방 또는 개선용 사료 조성물을 제공하는 것이다.Another object of the present invention is to provide a feed composition for the prevention or improvement of coronavirus infection disease, comprising the extract of Hyeoncho as an active ingredient.
이를 구체적으로 설명하면 다음과 같다. 한편, 본 발명에서 개시된 각각의 설명 및 실시형태는 각각의 다른 설명 및 실시 형태에도 적용될 수 있다. 즉, 본 발명에서 개시된 다양한 요소들의 모든 조합이 본 발명의 범주에 속한다. 또한, 하기 기술된 구체적인 서술에 의하여 본 발명의 범주가 제한된다고 볼 수 없다.This will be described in detail as follows. Meanwhile, each description and embodiment disclosed in the present invention may be applied to each other description and embodiment. That is, all combinations of the various elements disclosed herein fall within the scope of the present invention. In addition, it cannot be considered that the scope of the present invention is limited by the specific descriptions described below.
전술한 목적을 달성하기 위한 본 발명의 제1양태는, 현초 추출물을 유효성분으로 포함하는, 코로나바이러스 감염 질환의 예방 또는 치료용 약학 조성물을 제공한다.A first aspect of the present invention for achieving the above object provides a pharmaceutical composition for preventing or treating a coronavirus infection disease, comprising an extract of Hyeoncho as an active ingredient.
또한, 본 발명의 제2양태는 현초 추출물을 유효성분으로 포함하는, 코로나바이러스에 대한 항바이러스용 약학 조성물을 제공한다.In addition, the second aspect of the present invention provides a pharmaceutical composition for antiviral against coronavirus, comprising the extract of Hyeoncho as an active ingredient.
또한, 본 발명의 제3양태는 상기 약학 조성물을 인간을 제외한 개체에 투여하는 단계를 포함하는 코로나바이러스 감염 질환의 예방 또는 치료방법을 제공한다.In addition, a third aspect of the present invention provides a method for preventing or treating a coronavirus-infected disease comprising administering the pharmaceutical composition to an individual other than a human.
또한, 본 발명의 제4양태는 현초 추출물을 유효성분으로 포함하는 코로나바이러스 감염 질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the fourth aspect of the present invention provides a health functional food composition for the prevention or improvement of coronavirus infection disease comprising the extract of Hyeoncho as an active ingredient.
또한, 본 발명의 제5양태는 현초 추출물을 유효성분으로 포함하는 코로나바이러스 감염 질환의 예방 또는 개선용 사료 조성물을 제공한다.In addition, a fifth aspect of the present invention provides a feed composition for preventing or improving a coronavirus infection disease comprising a sagebrush extract as an active ingredient.
이하, 본 발명을 보다 자세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명의 용어, "현초"는 이질풀 Geranium thunbergii Siebold et Zuccarini 또는 기타 동속근연식물(쥐손이풀과 Geraniaceae)의 꽃이 피기 전 또는 꽃이 필 때 채취한 것을 의미한다. 구체적으로, 노관초 (老)라고도 부르며, 지상부로 줄기와 여기에 대생한 잎이다. 줄기는 가늘고 길며 녹갈색을 띠고 잎과 줄기에 연한 털이 있다. 잎은 손바닥 모양으로 3~5갈래로 갈라져 있으며 길이 2~4cm이다. 긴 잎자루가 있고 회황록색~회갈색을 띠며 열편은 긴 타원형 또는 도란형이고 둔한 거치가 있다. 냄새가 거의 없고 맛은 떫다.As used in the present invention, the term "Hyuncho" means that Geranium thunbergii Siebold et Zuccarini or other closely related plants (Geraniaceae) are collected before or when flowers bloom. Specifically, it is also called Nogwancho (老), and it is the above-ground part of the stem and the opposite leaves. Stems are thin and long, greenish-brown, with soft hairs on leaves and stems. The leaves are palm-shaped, divided into 3-5 branches, and are 2-4 cm long. It has a long petiole and is grayish-yellow-green to grayish-brown, and the lobe is long oval or obovate, with dull serrations. It has almost no odor and the taste is astringent.
본 발명의 용어, "추출물"은 액체 또는 고체 혼합물로부터 용매에 의해 분리된 물질을 의미한다.As used herein, the term "extract" means a substance separated by a solvent from a liquid or solid mixture.
상기 현초 추출물은 물, 탄소수 1 내지 6의 알코올 중에서 선택된 1종 이상의 용매로 추출하는 것일 수 있다. 구체적으로, 추출용매로 물, 알코올, 벤젠, 에테르, 석유에테르, 아세트산에틸, 또는 메탄올을 포함는 것일 수 있다.The Hyeoncho extract may be extracted with one or more solvents selected from water and alcohols having 1 to 6 carbon atoms. Specifically, the extraction solvent may include water, alcohol, benzene, ether, petroleum ether, ethyl acetate, or methanol.
본 발명의 용어, "코로나바이러스(Coronavirus)"는 코로나바이러스 과(Family Coronaviridae)에 속하는 바이러스들을 지칭하며 일반적으로 조류뿐만 아니라 사람을 포함한 다양한 포유류에서도 발견된다. 사람에게 감기를 일으키는 3대 바이러스 중 하나로, 전자현미경으로 봤을 때 바이러스 입자 표면이 돌기처럼 튀어나와 있는데 이 모양이 마치 왕관이나 태양의 코로나를 연상시킨다고 하여 라틴어로 왕관을 뜻하는 코로나(corona)에서 파생되 명명되었다. 코로나바이러스는 그 종이 다양하고, 바이러스의 특성과 숙주에 따라서 호흡기와 소화기 감염병을 모두 유발하는 것을 의미한다. 구체적으로, 최근 사람에서는 전 세계적으로 문제시되었던 사스(SARS)와 메르스(MERS)처럼 중증의 호흡기 증상을 유발하는 원인체로서 코로나바이러스가 주목받고 있다.As used herein, the term "coronavirus (Coronavirus)" refers to viruses belonging to the family Coronaviridae and is generally found in birds as well as various mammals including humans. It is one of the three major viruses that cause colds in humans, and when viewed through an electron microscope, the surface of the virus particles protrude like a protrusion. was renamed Coronaviruses are diverse in their species, and depending on the nature and host of the virus, it means that it causes both respiratory and digestive infectious diseases. Specifically, recently, in humans, coronavirus is attracting attention as a causative agent that causes severe respiratory symptoms like SARS and MERS, which have been a worldwide problem.
상기 코로나바이러스는 사스코로나바이러스-2(SARS-CoV-2)인 것일 수 있으나, 이에 제한되지 않는다.The coronavirus may be SARS-CoV-2, but is not limited thereto.
본 발명의 용어, "사스코로나바이러스-2(SARS-CoV-2)"는 2019년 12월 중국 우한에서 처음 발생한 뒤 중국 전역과 전 세계로 확산된 호흡기 감염질환이다. 구체적으로, 초기에는 원인을 알 수 없는 호흡기 전염병으로만 알려졌으나, 세계보건기구(WHO)가 2020년 1월 9일 해당 폐렴의 원인이 새로운 유형의 코로나바이러스(SARS-CoV-2, 국제바이러스분류위원회 2월 11일 명명)라고 밝히면서 병원체가 확인되었다. 새로운 유형의 코로나바이러스(SARS-CoV-2)에 의한 호흡기 감염질환으로, 사스코로나바이러스-2(SARS-CoV-2)는 감염자의 비말(침방울)이 호흡기나 눈·코·입의 점막으로 침투될 때 전염된다. 감염되면 약 2~14일(추정)의 잠복기를 거친 뒤 발열(37.5도) 및 기침이나 호흡곤란 등 호흡기 증상, 폐렴이 주증상으로 나타나지만 무증상 감염 사례 빈도도 높게 나오고 있다. As used herein, the term "SARS-CoV-2" is a respiratory infectious disease that first occurred in Wuhan, China in December 2019 and has spread throughout China and the world. Specifically, it was initially known only as a respiratory infectious disease of unknown cause, but on January 9, 2020, the World Health Organization (WHO) announced that the cause of the pneumonia was a new type of coronavirus (SARS-CoV-2, International Classification of Viruses). The pathogen was identified as the committee named it on February 11). It is a respiratory infection caused by a new type of coronavirus (SARS-CoV-2). is contagious when After an incubation period of about 2 to 14 days (estimated), the main symptoms are fever (37.5 degrees), respiratory symptoms such as cough or shortness of breath, and pneumonia, but the frequency of asymptomatic infections is also high.
본 발명의 용어, "코로나바이러스 감염 질환"은 코로나바이러스에 감염되어 나타나는 증상 또는 질병을 의미한다. 구체적으로, 몸살, 인후통, 설사, 투통, 결막염, 미각 또는 후각 상실 피부 발진, 손가락 또는 발가락 변색, 호흡곤란, 가슴통증, 언어 또는 운동장애, 감기, 폐렴, 당뇨병, 심혈관계 질환, 면역계 손상, 고혈압, 신부전, 백혈구 감소증, 림푸구 감소증, 메스꺼움 또는 구토, 또는 호흡기 질환을 포함할 수 있다.As used herein, the term "coronavirus-infected disease" refers to symptoms or diseases caused by infection with a coronavirus. Specifically, body aches, sore throat, diarrhea, headache, conjunctivitis, loss of taste or smell, skin rash, finger or toe discoloration, difficulty breathing, chest pain, speech or movement disorder, cold, pneumonia, diabetes, cardiovascular disease, immune system damage, high blood pressure , renal failure, leukopenia, lymphopenia, nausea or vomiting, or respiratory disease.
본 발명의 용어, "예방"은 본 발명에 따른 조성물의 투여에 의해 바이러스에 의한 발병을 억제시키거나 또는 지연시키는 모든 행위를 의미한다.As used herein, the term “prevention” refers to any act of inhibiting or delaying the onset of a virus by administering the composition according to the present invention.
본 발명의 용어, "개선"은 본 발명에 따른 조성물을 투여로 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다.As used herein, the term "improvement" refers to any action that at least reduces a parameter, for example, the severity of a symptom, associated with a condition to be treated by administration of a composition according to the present invention.
본 발명의 용어, "치료"는 상기 조성물의 투여에 의해 바이러스에 의한 발병 개체의 증상이 호전되거나 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term "treatment" refers to any action in which the symptoms of a virus-infected individual are improved or beneficially changed by administration of the composition.
본 발명의 용어, "항바이러스"는 바이러스의 증식을 억제하는 작용을 의미한다. 구체적으로, 바이러스는 식물, 동물, 세균 등이 살아있는 세포에 기생하여 그 세포에서만 증식한다. 가지고 있는 핵산의 종류에 따라 DNA 바이러스, RNA 바이러스로 구별된다. 어느 것이나 수백 μm 이하로 아주작다. 항바이러스는 이러한 바이러스를 미리 막아주기 위한 처방일 수 있고, 바이러스가 감염되더라도 발병까지는 이르지 못하게 하는 것일 수 있다.As used herein, the term "antiviral" refers to the action of inhibiting the proliferation of viruses. Specifically, the virus parasitizes in living cells of plants, animals, bacteria, and the like, and proliferates only in those cells. Depending on the type of nucleic acid they have, they are divided into DNA viruses and RNA viruses. All are very small, less than a few hundred μm. Antivirus may be a prescription to prevent these viruses in advance, and may prevent the virus from reaching the onset even if it is infected.
상기 목적을 달성하기 위한 본 발명의 또 다른 실시 양태는 상기 현초 추출물을 유효성분으로 포함하는 코로나바이러스 감염 질환의 예방 또는 치료, 또는 항바이러스용 약학 조성물을 제공한다. Another embodiment of the present invention for achieving the above object provides a pharmaceutical composition for the prevention or treatment of coronavirus infection, or antiviral pharmaceutical composition comprising the extract of Hyeoncho as an active ingredient.
본 발명의 조성물은 약학적으로 허용 가능한 염을 추가로 포함할 수 있다.The composition of the present invention may further include a pharmaceutically acceptable salt.
본 발명의 약학 조성물은, 약학적으로 허용 가능한 담체, 부형제 또는 희석제를 추가로 포함할 수 있는데, 상기 담체는 비자연적 담체(non-naturallyoccuring carrier)를 포함할 수 있다.The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient or diluent, wherein the carrier may include a non-naturallyoccuring carrier.
본 발명의 용어, "약학적으로 허용 가능한 염"은 양이온과 음이온이 정전기적 인력에 의해 결합하고 있는 물질인 염 중에서도 약학적으로 사용될 수 있는 형태의 염을 의미하며, 통상적으로 금속염, 유기염기와의 염, 무기산과의 염, 유기산과의 염, 염기성 또는 산성 아미노산과의 염 등이 될 수 있다. 예를 들어, 금속염으로는 알칼리 금속염(나트륨염, 칼륨염 등), 알칼리 토금속염(칼슘염, 마그네슘염, 바륨염 등), 알루미늄염 등이 될 수 있고; 유기염기와의 염으로는 트리에틸아민, 피리딘, 피콜린, 2,6-루티딘, 에탄올아민, 디에탄올아민, 트리에탄올아민, 시클로헥실아민, 디시클로헥실아민, N,N-디벤질에틸렌디아민 등과의 염이 될 수 있으며; 무기산과의 염으로는 염산, 브롬화수소산, 질산, 황산, 인산 등과의 염이 될 수 있고; 유기산과의 염으로는 포름산, 아세트산, 트리플루오로아세트산, 프탈산, 푸마르산, 옥살산, 타르타르산, 말레인산, 시트르산, 숙신산, 메탄술폰산, 벤젠술폰산, p-톨루엔술폰산 등과의 염이 될 수 있으며; 염기성 아미노산과의 염으로는 아르기닌, 라이신, 오르니틴 등과의 염이 될 수 있고; 산성 아미노산과의 염으로는 아스파르트산, 글루탐산 등과의 염이 될 수 있다.As used herein, the term "pharmaceutically acceptable salt" refers to a salt in a form that can be used pharmaceutically among salts, which are substances in which a cation and an anion are combined by electrostatic attraction, and is usually a metal salt, an organic base and salts, salts with inorganic acids, salts with organic acids, salts with basic or acidic amino acids, and the like. For example, the metal salt may be an alkali metal salt (sodium salt, potassium salt, etc.), alkaline earth metal salt (calcium salt, magnesium salt, barium salt, etc.), an aluminum salt or the like; Salts with organic bases include triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N,N-dibenzylethylenediamine salts with, etc.; salts with inorganic acids may be salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like; Salts with organic acids may be salts with formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and the like; Salts with basic amino acids may be salts with arginine, lysine, ornithine and the like; The salt with an acidic amino acid may be a salt with aspartic acid, glutamic acid, or the like.
구체적으로, 상기 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트, 폴리카프로락톤(polycaprolactone), 폴리락틱액시드(Poly Lactic Acid), 폴리-L-락틱액시드(poly-L-lactic acid), 광물유 등을 들 수 있다. 상기 약학 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있으며, 담체의 형태로는 각종 부정형의 담체, 마이크로 스피어, 나노파이버 등을 포함할 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 상기 추출물과 이의 분획물들에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘 카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제들도 사용될 수 있다. 경구투여를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제 등이 포함될 수 있다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 본 발명의 약학 조성물에 포함된 현초 추출물 또는 이의 약학적으로 허용 가능한 염의 함량은 특별히 제한되지 않는다.Specifically, carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium Silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, polycaprolactone, polylactic acid Lactic Acid), poly-L-lactic acid, and mineral oil. The pharmaceutical composition may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injection solutions, respectively, according to conventional methods. The form may include various amorphous carriers, microspheres, nanofibers, and the like. In the case of formulation, it can be prepared using a diluent or excipient such as a filler, extender, binder, wetting agent, disintegrant, surfactant, etc. commonly used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the extract and its fractions, for example, starch, calcium carbonate, It may be prepared by mixing sucrose or lactose, gelatin, or the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid formulations for oral administration include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. The content of the Hyeoncho extract or a pharmaceutically acceptable salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited.
상기 목적을 달성하기 위한 본 발명의 또 다른 실시 양태는 상기 약학 조성물을 인간을 제외한 개체에 투여하는 단계를 포함하는 코로나바이러스 감염 질환의 예방 또는 치료방법을 제공한다.Another embodiment of the present invention for achieving the above object provides a method for preventing or treating a coronavirus infection disease comprising administering the pharmaceutical composition to an individual other than humans.
이때, 상기 "현초", "항바이러스", "코로나바이러스", "코로나바이러스 감염 질환", "예방", "개선" 및 "치료"에 대한 설명은 상기 서술한 바와 같다.At this time, the descriptions of "prevention", "antiviral", "coronavirus", "coronavirus infection disease", "prevention", "improvement" and "treatment" are the same as those described above.
본 발명의 용어, "개체"는 코로나바이러스 감염에 의해 발병하였거나, 발병할 수 있는 쥐, 생쥐, 가축 등의 모든 동물을 의미한다. 구체적인 예로, 포유동물일 수 있다.As used herein, the term "individual" means all animals, such as rats, mice, livestock, etc., that have or can be caused by coronavirus infection. As a specific example, it may be a mammal.
본 발명의 용어, "투여"는 어떠한 적절한 방법으로 개체에 소정의 물질을 도입하는 것을 의미하며, 본 발명의 약학 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 경구 또는 비경구 투여될 수 있다. 또한, 약학 조성물은 활성 물질이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수 있다.As used herein, the term "administration" means introducing a predetermined substance into a subject by any suitable method, and the administration route of the pharmaceutical composition of the present invention is oral or parenteral through any general route as long as it can reach the target tissue. It can be administered orally. In addition, the pharmaceutical composition may be administered by any device capable of transporting the active agent to a target cell.
본 발명의 용어, "투여량"은 개체의 나이, 성별, 체중에 따라달라질 수 있으며, 당업자에 의해 용이하게 결정될 수 있다. 구체적으로, 본 발명의 약학 조성물은 경구 또는 비경구로 투여될 수 있다. 또한, 약학 조성물의 투여량은 투여 경로, 질병의 정도, 성별, 체중, 연령 등의 여러 관련인자와 함께, 활성 성분인 조성물의 종류에 따라 당업자에 의해 결정될 수 있으므로 사익 투여량에 의해 본 발명의 범위가 한정되는 것은 아니다.As used herein, the term “administration amount” may vary depending on the age, sex, and weight of an individual, and may be readily determined by those skilled in the art. Specifically, the pharmaceutical composition of the present invention may be administered orally or parenterally. In addition, the dosage of the pharmaceutical composition may be determined by a person skilled in the art according to the type of the composition as an active ingredient, along with several related factors such as the route of administration, the degree of disease, sex, weight, age, etc. The scope is not limited.
본 발명의 용어, "투여방법"은 경구, 정맥 내, 피하, 피 내, 비강 내, 복강 내, 근육 내, 경피 등 다양한 방법을 의미한다.As used herein, the term "administration method" refers to various methods such as oral, intravenous, subcutaneous, intradermal, intranasal, intraperitoneal, intramuscular, and transdermal.
상기 목적을 달성하기 위한 본 발명의 또 다른 실시 양태는 현초 추출물을 유효성분으로 포함하는 코로나바이러스 감염 질환의 예방 또는 개선용, 또는 항바이러스용 건강기능식품 조성물을 제공한다.Another embodiment of the present invention for achieving the above object provides a health functional food composition for the prevention or improvement of coronavirus infection disease, or antiviral, comprising the extract of sagebrush as an active ingredient.
본 발명의 조성물은 식품학적으로 허용 가능한 염을 추가로 포함할 수 있다. The composition of the present invention may further include a food pharmaceutically acceptable salt.
상기 목적을 달성하기 위한 본 발명의 다른 실시 양태는 본 발명에 따른 현초 추출물은 우수한 코로나바이러스 감염 질환의 예방 또는 치료 효과를 나타내므로, 코로나바이러스 감염 질환 예방 또는 치료, 항바이러스용을 목적으로 식품 조성물에 포함될 수 있으며, 상기 식품 조성물은 일상적으로 섭취하는 것이 가능하기 때문에 항바이러스, 코로나바이러스 감염 질환의 예방 또는 치료에 대하여 높은 효과를 기대할 수 있다.Another embodiment of the present invention for achieving the above object is that the extract according to the present invention exhibits an excellent prevention or treatment effect of a coronavirus infection disease, and thus a food composition for the purpose of preventing or treating a coronavirus infection disease, antiviral It may be included in, and since the food composition can be consumed on a daily basis, a high effect can be expected for the prevention or treatment of antiviral, coronavirus-infected diseases.
이때, 상기 "현초", "항바이러스", "코로나바이러스", "코로나바이러스 감염 질환", "예방", "개선" 및 "치료"에 대한 설명은 상기 서술한 바와 같다.At this time, the descriptions of "prevention", "antiviral", "coronavirus", "coronavirus infection disease", "prevention", "improvement" and "treatment" are the same as those described above.
본 발명의 용어, "건강기능식품"은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, '기능성'은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻는 것을 의미한다. 한편, 건강식품은 일반식품에 비해 적극적인 건강유지나 증진 효과를 가지는 식품을 의미하고, 건강보조식품은 건강 보조 목적의 식품을 의미하는데, 경우에 따라, 건강기능식품, 건강식품, 건강보조식품의 용어는 혼용될 수 있다.As used herein, the term “health functional food” refers to food manufactured and processed using raw materials or ingredients useful for the human body in accordance with Act No. 6727 of the Health Functional Food Act, and 'functionality' refers to the structure of the human body. And it means to obtain a useful effect for health use, such as regulating nutrients for function or physiological action. On the other hand, health food means food that has an active health maintenance or promotion effect compared to general food, and health supplement means food for the purpose of health supplementation. In some cases, the terms health functional food, health food and health supplement food can be mixed.
본 발명의 현초 추출물 또는 이의 식품학적으로 허용 가능한 염은 그대로 첨가되거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다.The extract of the present invention or a pharmaceutically acceptable salt thereof may be added as it is or may be used with other foods or food ingredients, and may be appropriately used according to a conventional method.
본 발명의 식품은 당 업계에서 통상적으로 사용되는 방법에 의하여 제조 가능하며, 상기 제조 시에는 당 업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 구체적으로, 상기 식품 조성물은 생리학적으로 허용 가능한 담체를 추가로 포함할 수 있는데, 담체의 종류는 특별히 제한되지 않으며 당해 기술 분야에서 통상적으로 사용되는 담체라면 어느 것이든 사용할 수 있다. 또한, 상기 식품 조성물은 방부제, 살균제, 산화방지제, 착색제, 발색제, 표백제, 조미료, 감미료, 향료, 팽창제, 강화제, 유화제, 증점제, 피막제, 검기초제, 거품억제제, 용제, 개량제 등의 식품 첨가물을 포함할 수 있다. 상기 첨가물은 식품의 종류에 따라 선별되고 적절한 양으로 사용될 수 있다.The food of the present invention can be prepared by a method commonly used in the art, and at the time of manufacture, it can be prepared by adding raw materials and components commonly added in the art. Specifically, the food composition may further include a physiologically acceptable carrier, the type of carrier is not particularly limited and any carrier commonly used in the art may be used. In addition, the food composition contains food additives such as preservatives, disinfectants, antioxidants, colorants, coloring agents, bleaching agents, seasonings, sweeteners, flavoring agents, expanding agents, strengthening agents, emulsifying agents, thickeners, filming agents, gum base agents, foam inhibitors, solvents, and improving agents. may include The additive may be selected according to the type of food and used in an appropriate amount.
또한, 상기 식품의 제형은 식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 식품 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고 휴대성이 뛰어나므로, 본 발명의 식품은 항바이러스, 코로나바이러스 감염 질환 예방 또는 치료의 효과를 증진시키기 위한 보조제로 섭취가 가능하다.In addition, the formulation of the food may be prepared without limitation as long as it is a formulation recognized as a food. The food composition of the present invention can be prepared in various types of dosage forms, and unlike general drugs, it has the advantage of not having side effects that may occur during long-term administration of drugs by using food as a raw material, and is excellent in portability. Food can be ingested as a supplement to enhance the effectiveness of antiviral or coronavirus-infected disease prevention or treatment.
본 발명의 현초 추출물 또는 이의 식품학적으로 허용 가능한 염은 항바이러스, 및 코로나바이러스 감염 질환 예방 또는 치료 효과를 나타낼 수 있다면 식품 조성물에 다양한 중량%로 포함될 수 있다. 구체적으로 식품 조성물의 총 중량대비 0.00001 내지 100 중량% 또는 0.01 내지 80 중량%로 포함될 수 있으나, 이에 제한되지 않는다. 건강 및 위생을 목적으로 장기간 섭취할 경우에는 상기 범위 이하의 함량을 포함할 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.Hyeoncho extract of the present invention or a pharmaceutically acceptable salt thereof may be included in various weight % in the food composition if it can exhibit antiviral and coronavirus-infected disease prevention or treatment effects. Specifically, it may be included in an amount of 0.00001 to 100% by weight or 0.01 to 80% by weight relative to the total weight of the food composition, but is not limited thereto. In the case of long-term ingestion for health and hygiene purposes, it may contain an amount below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
상기 목적을 달성하기 위한 본 발명의 또 다른 실시 양태는 상기 현초 추출물을 유효성분으로 포함하는 항바이러스용, 또는 코로나바이러스 감염 질환의 예방 또는 치료용 사료 조성물을 제공한다. Another embodiment of the present invention for achieving the above object provides a feed composition for the prevention or treatment of antiviral, or coronavirus-infected disease comprising the extract of Hyeoncho as an active ingredient.
본 발명의 조성물은 식품학적으로 허용 가능한 염을 추가로 포함할 수 있다.The composition of the present invention may further include a food pharmaceutically acceptable salt.
이때, 상기 "현초", "항바이러스", "코로나바이러스", "코로나바이러스 감염 질환", "예방", "개선" 및 "치료"에 대한 설명은 상기 서술한 바와 같다.At this time, the descriptions of "prevention", "antiviral", "coronavirus", "coronavirus infection disease", "prevention", "improvement" and "treatment" are the same as those described above.
본 발명에 따른 현초 추출물은 우수한 항바이러스, 코로나바이러스 감염 질환의 예방 및 치료 효과를 나타내므로, 항바이러스, 및 코로나바이러스 감염 질환의 예방 및 치료를 목적으로 사료 조성물에 포함될 수 있으며, 상기 사료 조성물은 동물이 일상적으로 섭취하는 것이 가능하기 때문에 코로나바이러스 감염 질환 예방 또는 치료, 항바이러스에 대하여 높은 효과를 기대할 수 있다.Hyeoncho extract according to the present invention exhibits excellent antiviral, preventive and therapeutic effects of coronavirus-infected diseases, and thus may be included in a feed composition for the purpose of preventing and treating antiviral and coronavirus-infected diseases, the feed composition comprising Since it is possible for animals to consume it on a daily basis, a high effect can be expected for the prevention or treatment of coronavirus-infected diseases and antiviral.
본 발명의 용어, "사료"는 동물이 먹고, 섭취하며, 소화시키기 위한 또는 이에 적당한 임의의 천연 또는 인공 규정식, 한끼식 등 또는 상기 한끼식의 성분을 의미한다. 상기 사료의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용되는 사료를 사용할 수 있다. 상기 사료의 비제한적인 예로는, 곡물류, 근과류, 식품 가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류 또는 곡물 부산물류 등과 같은 식물성 사료; 단백질류, 무기물류, 유지류, 광물성류, 유지류, 단세포 단백질류, 동물성 플랑크톤류 또는 음식물 등과 같은 동물성사료를 들 수 있다. 이들은 단독으로 사용되거나 2종 이상을 혼합하여 사용될 수 있다.As used herein, the term "feed" means any natural or artificial diet, meal, etc., or a component of said meal, intended for or suitable for being eaten, consumed, and digested by an animal. The type of feed is not particularly limited, and feed commonly used in the art may be used. Non-limiting examples of the feed include plant feeds such as grains, root fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, gourds or grain by-products; and animal feeds such as proteins, inorganic materials, oils and fats, minerals, oils and fats, single cell proteins, zooplankton or food. These may be used alone or in mixture of two or more.
본 발명의 현초 추출물은 도 1 에 나타난 바와 같이, 인간의 ACE2단백질 수용체에 SARS-CoV-2의 스파이크(spike) 단백질간의 결합을 억제하므로, 코로나바이러스의 감염을 억제할 수 있다.As shown in FIG. 1 , the Hyeoncho extract of the present invention inhibits the binding between the spike protein of SARS-CoV-2 to the human ACE2 protein receptor, and thus can suppress the infection of the coronavirus.
본 발명의 용어, " 안지오텐신 전환효소 2(Angiotensin-converting enzyme 2, ACE2) 단백질 "은 메탈로카복시펩티다제 (metallo-carboxypeptidase)의 하나로, 안지오텐신 전환효소와 상동하는 1형 막관통 단백질이며, 진핵생물과 세균에서 발견할 수 있다. As used herein, the term "Angiotensin-converting enzyme 2 (ACE2) protein" is one of metallo-carboxypeptidase, a type 1 transmembrane protein homologous to angiotensin converting enzyme, and is a eukaryotic It can be found in living organisms and bacteria.
본 발명의 용어, "스파이크(spike) 단백질"은 외피 표면에 배열하는 돌기상 구조물을 의미한다. 구체적으로, 바이러스입자 표면에서 양자를 형태학적으로 구별하기 어렵지만 각각의 스파이크를 분리 정제하면, 형태학적 차이를 인식할 수 있고, 스파이크는 외피가 있는 바이러스의 숙주세포로의 흡착침입에 필수적인 역할을 한다.As used herein, the term "spike protein" refers to a dendritic structure arranged on the surface of the outer skin. Specifically, although it is difficult to morphologically distinguish between the two on the surface of the virus particle, if each spike is isolated and purified, the morphological difference can be recognized, and the spike plays an essential role in adsorption and invasion of the enveloped virus into the host cell. .
코로나바이러스는 바이러스 표면에 왕관처럼 튀어나온 스파이크 단백질이 사람에게 침입하는 중요한 병기이다. 우리몸에 있는 안지오텐신 전환효소2는 수용체 단백질로 코로나바이러스의 스파이크 단백질과 결합하여 인체에 침입해 감염을 일으킨다. 우리 몸의 단백질 안지오텐신 전환효소 2는 폐 손상을 막아주는 기능을 갖는데 ACE2의 수용체에 코로나바이러스 스파이크 단백질이 결합하여 바이러스가 우리 몸에 침투하면 중증급성호흡기증후군이 발병될 수 있다.Coronavirus is an important weapon in which the spike protein that protrudes like a crown on the surface of the virus invades humans. Angiotensin-converting
구체적인 일 실시예에서, 본 발명의 현초 추출물이 ACE2와 코로나바이러스 스파이크 단백질 간의 결합을 효과적으로 억제하는 것을 확인하였다.In a specific example, it was confirmed that the Hyeoncho extract of the present invention effectively inhibits the binding between ACE2 and the coronavirus spike protein.
따라서, 상기 구체적인 일 실시예를 통하여 본 발명의 현초 추출물은 ACE2 단백질이 코로나바이러스가 침투하는 통로이므로 ACE2 단백질과 코로나바이러스의 스파이크 단백질 간의 결합 억제 효과를 가지는 것을 확인할 수 있었으며, 이는 나아가 코로나바이러스 감염 질환의 예방 또는 치료용, 항바이러스 용도로 사용될 수 있음을 시사한다.Therefore, through the specific example above, it was confirmed that the Hyeoncho extract of the present invention has an effect of inhibiting the binding between the ACE2 protein and the spike protein of the coronavirus because the ACE2 protein is the passage through which the coronavirus penetrates, which furthermore is a coronavirus infection disease. It suggests that it can be used for the prevention or treatment of, or antiviral use.
본 발명의 현초 추출물은 사스코로나바이러스-2(SARS-CoV-2)와 같은 코로나바이러스의 감염을 억제하는 효과를 나타내므로, 상기 바이러스 질환을 예방 또는 치료를 위한 항바이러스제 개발에 이용될 수 있다.Since the extract of the present invention exhibits an effect of inhibiting infection of coronaviruses such as SARS-CoV-2 (SARS-CoV-2), it can be used to develop antiviral agents for preventing or treating the viral diseases.
도 1은 사스코로나바이러스-2(SARS-CoV-2)의 스파이크 단백질과 인간의 ACE2 단백질간의 결합 관계를 나타낸 모식도이다.
도 2는 본 발명의 현초 추출물의 농도에 따른 사스코로나바이러스-2(SARS-CoV-2)의 스파이크 단백질과 인간의 ACE2 단백질간의 결합 억제율을 나타낸 그래프이다.
도 3은 본 발명의 현초 추출물의 세포감염 억제를 나타낸 사진이다.1 is a schematic diagram showing the binding relationship between the spike protein of SARS coronavirus-2 (SARS-CoV-2) and the human ACE2 protein.
2 is a graph showing the inhibition rate of binding between the spike protein of SARS-CoV-2 (SARS-CoV-2) and the human ACE2 protein according to the concentration of the Hyeoncho extract of the present invention.
3 is a photograph showing the inhibition of cell infection of the Hyeoncho extract of the present invention.
이하, 실시예를 통하여 본 발명을 보다 상세히 설명하고자 한다. 이들 실시예는 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 범위가 이들 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail through examples. These Examples are for explaining the present invention in more detail, and the scope of the present invention is not limited by these Examples.
제조예 1: 현초 추출물 제조방법Preparation Example 1: Method for preparing an extract of Hyeoncho
10g의 현초(Geranium thunbergii Siebold et Zuccarini)를 건조한 후, 30-70%(v/v) 에탄올 100㎖을 용매로 첨가하여 2시간 동안 3회 환류 추출하고, 감압 농축하여 현초 추출물을 제조하였다.After drying 10 g of Huncho (Geranium thunbergii Siebold et Zuccarini), 100 ml of 30-70% (v/v) ethanol was added as a solvent, extracted under reflux three times for 2 hours, and concentrated under reduced pressure to prepare a Hyeoncho extract.
실시예 1: 현초 추출물의 사스코로나바이러스-2(SARS-CoV-2) 감염 억제 확인Example 1: Confirmation of inhibition of SARS-CoV-2 (SARS-CoV-2) infection of Hyeoncho extract
현초 추출물의 사스코로나바이러스-2(SARS-CoV-2) 감염 억제능을 확인하기 위하여 농도에 따른 ACE2와 사스코로나바이러스-2(SARS-CoV-2)의 스파이크 단백질간의 결합 억제율을 확인하였다.In order to confirm the SARS-CoV-2 infection inhibitory ability of the extract of Hyeoncho, the binding inhibition rate between the spike protein of ACE2 and SARS-CoV-2 (SARS-CoV-2) according to the concentration was confirmed.
구체적으로, 인간의 ACE2단백질과 사스코로나바이러스-2(SARS-CoV-2)의 스파이크 단백질간의 결합 억제를 확인하기 위해 현초 추출물을 농도별(1.56, 3.12, 6.25, 12.5, 25, 50, 100 μg/ml)로 첨가한 뒤 결합 억제율을 확인하였다. 이때, 양성대조군으로 항 스파이크(spike) 단백질(6.25, 12.5, 25, 50, 100 ng)을 사용하였다.Specifically, in order to confirm the inhibition of binding between human ACE2 protein and the spike protein of SARS-CoV-2, Hyeoncho extract by concentration (1.56, 3.12, 6.25, 12.5, 25, 50, 100 μg) /ml) was added to confirm the binding inhibition rate. In this case, anti-spike proteins (6.25, 12.5, 25, 50, 100 ng) were used as a positive control.
도 2에 나타난 바와 같이, 본 발명의 현초 추출물은 가장적은 양의 1.56 μg/ml으로도 인간의 ACE2단백질과 사스코로나바이러스-2(SARS-CoV-2)의 스파이크 단백질간의 결합을 억제 하였고, 양성 대조군 대비 현초 추출물의 결합 억제율이 우수하며, 농도 의존적으로 결합을 억제하는 것을 확인하였다. As shown in Figure 2, the Hyeoncho extract of the present invention inhibited the binding between the spike protein of human ACE2 protein and SARS-CoV-2 (SARS-CoV-2) even in the smallest amount of 1.56 μg / ml, positive It was confirmed that the binding inhibition rate of the Hyeoncho extract compared to the control was excellent, and the binding was inhibited in a concentration-dependent manner.
따라서, 본 발명의 현초 추출물은 사스코로나바이러스-2(SARS-CoV-2)에 대한 항바이러스 활성을 가지고 있음을 확인할 수 있었다.Therefore, it was confirmed that the Hyeoncho extract of the present invention has antiviral activity against SARS-CoV-2 (SARS-CoV-2).
실시예 2: 현초 추출물의 세포감염 억제Example 2: Inhibition of cell infection of Hyeoncho extract
24-well TC 플레이트에 hACE2/TMPRSS2 과발현 HEK293 세포(1×105cells/well)를 접종(Cell seeding)하였다. 18~20시간 후에, 현초(50 ㎍/㎖ 농도) 또는 SARS-CoV-2 스파이크 단백질 항체(1 ㎍/㎖)를 GFP 발현한 SARS-CoV-2 스파이크 유사형 렌티바이러스(SARS-CoV-2 Spike-Pseudotyped Lentivirus) (MOI:1)에 37°C에서 한 시간 동안 인큐베이션 한 후, hACE2/TMPRSS2 과발현 HEK293 세포에 접종하였다. 현초 추출물과 함께 SARS-CoV-2 GFP바이러스를 접종한 2시간 후, 세포에서 접종액을 제거하였다. 이후 PBS로 3회 세척한 후, 10% FBS 첨가된 DMEM으로 교체해 주었다. 음성 대조구는 10% FBS가 첨가된 DMEM만을 처리하였다. 양성 대조구는 SARS-CoV-2 스파이크 항체를 사용하였다. 72시간 후 바이러스 감염 정도를 형광현미경을 이용하여 바이러스의 감염 억제를 확인하였다.In a 24-well TC plate, hACE2/TMPRSS2 overexpressing HEK293 cells (1×105 cells/well) were inoculated (cell seeding). After 18-20 hours, SARS-CoV-2 spike-like lentivirus (SARS-CoV-2 Spike) expressing GFP-expressing SARS-CoV-2 spike protein antibody (1 μg/ml) or SARS-CoV-2 spike protein antibody (SARS-CoV-2 Spike) -Pseudotyped Lentivirus) (MOI: 1) at 37 °C for one hour, and then inoculated into hACE2/TMPRSS2-overexpressing HEK293 cells. After 2 hours of inoculation with SARS-CoV-2 GFP virus with Hyeoncho extract, the inoculum was removed from the cells. After washing 3 times with PBS, it was replaced with DMEM containing 10% FBS. A negative control was treated only with DMEM supplemented with 10% FBS. As a positive control, SARS-CoV-2 spike antibody was used. After 72 hours, the degree of virus infection was checked using a fluorescence microscope to confirm the inhibition of virus infection.
도 3에 나타난 바와 같이, 세포에 SARS-CoV-2감염시켜 면역 형광에 의해 검사된 바이러스 감염은 세포의 세포질에서 검출되었으나, 본 발명의 현초 추출물은 세포에 SARS-CoV-2감염이 검출되지 않아, 항바이러스 효과를 나타내는 것을 확인하였다. As shown in FIG. 3 , the virus infection tested by immunofluorescence by SARS-CoV-2 infection in cells was detected in the cytoplasm of the cells, but the Hyeoncho extract of the present invention did not detect SARS-CoV-2 infection in the cells. , it was confirmed that it exhibits an antiviral effect.
본 발명의 실시예 1 내지 실시예 2를 종합하면, 본 발명의 현초 추출물은 인간의 ACE2단백질과 사스코로나바이러스-2(SARS-CoV-2)의 스파이크 단백질간의 결합을 억제 하여, 사스코로나바이러스-2(SARS-CoV-2)에 대한 항바이러스 효과가 있는 것을 확인할 수 있다.Summarizing Examples 1 to 2 of the present invention, the Hyeoncho extract of the present invention inhibits the binding between human ACE2 protein and the spike protein of SARS-CoV-2, SARS-CoV-2 It can be confirmed that there is an antiviral effect on 2 (SARS-CoV-2).
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, those skilled in the art to which the present invention pertains will understand that the present invention may be embodied in other specific forms without changing the technical spirit or essential characteristics thereof. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention, rather than the above detailed description, all changes or modifications derived from the meaning and scope of the following claims and their equivalents.
Claims (6)
A pharmaceutical composition for the prevention or treatment of coronavirus-infected diseases, comprising an extract of Hyeoncho as an active ingredient.
상기 코로나바이러스는 사스코로나바이러스-2(SARS-CoV-2)인 것인, 약학 조성물.
According to claim 1,
The coronavirus is SARS-CoV-2 (SARS-CoV-2), the pharmaceutical composition.
A pharmaceutical composition for antiviral against coronavirus, comprising the extract of Hyeoncho as an active ingredient.
A method of preventing or treating a coronavirus-infected disease comprising administering the pharmaceutical composition of claim 3 to a subject other than a human.
A health functional food composition for the prevention or improvement of coronavirus-infected diseases, comprising an extract of Hyeoncho as an active ingredient.
A feed composition for the prevention or improvement of coronavirus-infected diseases comprising an extract of Hyeoncho as an active ingredient.
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PCT/KR2021/017407 WO2022131603A1 (en) | 2020-12-17 | 2021-11-24 | Antiviral composition containing geranium herb extract as active ingredient |
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