KR102665503B1 - Composition for the prevention or treatment of SARS-CoV-2 infection, comprising the extract of Galla rhois as an active ingredient - Google Patents
Composition for the prevention or treatment of SARS-CoV-2 infection, comprising the extract of Galla rhois as an active ingredient Download PDFInfo
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- KR102665503B1 KR102665503B1 KR1020210049352A KR20210049352A KR102665503B1 KR 102665503 B1 KR102665503 B1 KR 102665503B1 KR 1020210049352 A KR1020210049352 A KR 1020210049352A KR 20210049352 A KR20210049352 A KR 20210049352A KR 102665503 B1 KR102665503 B1 KR 102665503B1
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/22—Anacardiaceae (Sumac family), e.g. smoketree, sumac or poison oak
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23V2200/00—Function of food ingredients
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Abstract
본 발명은 오배자 추출물의 코로나 바이러스(SARS-CoV-2) 감염에 대한 예방, 개선 또는 치료 효과를 확인하여 오배자 추출물을 이용하여 전 세계적으로 문제가 되고 있는 코로나 바이러스감염증-19(COVID-19)을 예방, 개선 또는 치료할 수 있는 조성물을 제조하는 것을 목적으로 한다.The present invention confirms the prevention, improvement, or treatment effect of the extract of the shipwreck against coronavirus (SARS-CoV-2) infection and prevents coronavirus disease 19 (COVID-19), which is a worldwide problem, using the extract of the shipwreck. The purpose is to prepare a composition that can prevent, improve or treat.
Description
본 발명은 오배자(Galla rhois) 추출물을 유효성분으로 포함하는 코로나 바이러스(SARS-CoV-2) 감염의 예방, 개선 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing, improving, or treating coronavirus (SARS-CoV-2) infection containing Galla rhois extract as an active ingredient.
2019년 12월 중국에서 발생한 집단 폐렴의 원인인 코로나 바이러스 감염증(SARS-CoV-2, COVID-19, 이하 코로나19)의 전 세계적인 유행으로 코로나19 사태의 장기화 및 재유행 가능성이 높아지는 추세이다. 세계보건기구(World Health Organization, WHO)는 2020년 1월 30일 국제적 공중보건 비상사태를 선언하였으며 치료제 및 백신 개발을 위해 총력을 기울이고 있고, 국내에서는 감염병 위기경보를 ‘심각’으로 격상하여 대응하고 있다.Due to the global spread of coronavirus infection (SARS-CoV-2, COVID-19, hereinafter referred to as COVID-19), which is the cause of the mass pneumonia that occurred in China in December 2019, the possibility of a prolonged COVID-19 outbreak and a resurgence is increasing. The World Health Organization (WHO) declared an international public health emergency on January 30, 2020, and is making every effort to develop treatments and vaccines. In Korea, the infectious disease crisis alert was raised to 'serious' to respond. there is.
현재 전세계적으로 문제되고 있는 코로나 바이러스는 SARS-CoV-2 감염에 의한 호흡기 증후군이라 정의되고 있으며, 질병 분류는 법정감염병 제1급감염병 신종감염병증후군 및 질병 코드는 U07.1이다. 2019년 12월에 중국 우한의 폐렴 환자들에서 분리된 바이러스는 전체 유전체 염기서열 분석 결과 베타 코로나 바이러스에 속하고 SARS-CoV와 구별되는 새로운(novel) 코로나 바이러스로 밝혀졌다. 이 바이러스의 염기 서열은 SARS-CoV와 MERS-CoV의 염기서열과 각각 79.0%, 51.8% 일치하였으며, 박쥐의 SARS-like coronavirus (bat-SL-CoVC45)와는 약 87.6~89% 일치하여 가장 유사하였다(박수은. 코로나 바이러스감염증-19의 바이러스(SARS-CoV-2) 특징, 전파 및 임상 양상. Pediatr Infect Vaccine. 2020). SARS-CoV-2는 SARS-CoV와는 다르게 스파이크 단백질이 활성화되어 바이러스와 세포막이 결합하는데 매우 유리한 특징이 있다. 이 병원체는 SARS-CoV-2로 명명되었고, 이는 코로나 바이러스과(Coronaviridae)에 속하는 RNA 바이러스이며, 전파 경로는 현재까지 비말(침방울), 접촉을 통한 전파로 알려져있다. 따라서, 기침이나 재채기를 할 때 생긴 비말(침방울)을 통한 전파 등 또는 코로나19 바이러스에 오염된 물건을 만진 뒤 눈, 코, 입을 만짐으로써 전파되고 있다고 알려져 있다. 전세계 치명률은 약 3.57%(WHO, 8. 16 기준)이고, 단 국가별·연령별 치명률 수준은 매우 상이하다. 고령, 면역기능이 저하된 환자, 기저질환을 가진 환자가 주로 중증, 사망을 초래한다.The coronavirus, which is currently a worldwide problem, is defined as a respiratory syndrome caused by SARS-CoV-2 infection, and the disease classification is a new infectious disease syndrome, a class 1 statutory infectious disease, and the disease code is U07.1. The virus isolated from pneumonia patients in Wuhan, China in December 2019 was found to be a novel coronavirus belonging to the beta coronavirus family and distinct from SARS-CoV as a result of whole genome sequencing. The nucleotide sequence of this virus was 79.0% and 51.8% identical to the nucleotide sequences of SARS-CoV and MERS-CoV, respectively, and was most similar to the bat SARS-like coronavirus (bat-SL-CoVC45), approximately 87.6 to 89% identical. (Park Soo-eun. Characteristics, transmission and clinical aspects of the coronavirus disease-19 virus (SARS-CoV-2). Pediatr Infect Vaccine. 2020). Unlike SARS-CoV, SARS-CoV-2 has an activated spike protein, which is very advantageous in binding the virus to the cell membrane. This pathogen was named SARS-CoV-2, which is an RNA virus belonging to the Coronaviridae family, and the route of transmission is currently known to be through droplets and contact. Therefore, it is known that it is spread through droplets produced when coughing or sneezing, or by touching an object contaminated with the COVID-19 virus and then touching the eyes, nose, or mouth. The global fatality rate is approximately 3.57% (WHO, as of August 16), but the fatality rate levels by country and age are very different. Elderly, patients with weakened immune function, and patients with underlying diseases mainly suffer from severe disease and death.
코로나 바이러스의 잠복기는 1~14일(평균 4~7일)이고, 진단 기준으로는 진단을 위한 검사기준에 따라 감염병 병원체 감염이 확인된 사람의 검체에서 바이러스 분리 또는 검체에서 특이 유전자 검출하여 진단하고 있다. 코로나 바이러스의 증상으로는 발열, 권태감, 기침, 호흡곤란 및 폐렴 등 경증에서 중증까지 다양한 호흡기감염증이 나타나며, 그 외 가래, 인후통, 두통, 객혈과 오심, 설사 등도 나타난다. 현재 수액 보충, 해열제 등 보존적 치료를 하는 것 외에 특이적인 항바이러스제가 없는 것이 현실이다.The incubation period of the coronavirus is 1 to 14 days (average 4 to 7 days), and the diagnosis is made by isolating the virus from a sample of a person confirmed to be infected with an infectious disease pathogen or detecting a specific gene in the sample according to the testing standards for diagnosis. there is. Symptoms of coronavirus include a variety of respiratory infections ranging from mild to severe, such as fever, malaise, cough, difficulty breathing, and pneumonia. Other symptoms include phlegm, sore throat, headache, hemoptysis, nausea, and diarrhea. Currently, there is no specific antiviral agent other than conservative treatment such as fluid supplementation and antipyretics.
국내외 코로나19 치료제 개발 방향은 크게 4가지로 기존 약물의 사용범위를 확대하는 ‘약물재창출’, 완치자 혈액으로부터 면역글로불린을 확보해 생산하는 방식인 ‘혈장치료제’, 회복기 환자 혈액으로 코로나19 항체를 발굴하는 ‘항체치료제’, 바이러스 표적 약물을 개발하는 ‘신약개발’ 방식 등이 있다.There are four major directions for the development of COVID-19 treatments at home and abroad: ‘drug re-creation’, which expands the scope of use of existing drugs, ‘plasma therapy’, which secures and produces immunoglobulins from the blood of recovered patients, and COVID-19 antibodies from the blood of convalescent patients. There are methods such as discovering ‘antibody treatments’ and ‘new drug development’ methods that develop virus-targeting drugs.
그러나 약물재창출 후보물질들은 기존에 다른 질병 및 바이러스 질환을 대상으로 개발되었기 때문에 코로나19 치료제로 사용할 경우 부작용이 나타날 가능성이 존재하며, 혈장치료제의 경우 완치자의 혈장이 지속적으로 필요하다는 점, 인간 단클론 항체 치료제의 경우 화합물 기반의 치료제에 비해 제조 시간이 많이 걸리고 대량생산이 어려운 단점들을 가지고 있다. 따라서, 코로나19 사태를 근복적으로 해결하기 위하여 안전성이 높으며 효과적인 치료제 개발이 절실한 상태이다.However, since drug repurposing candidates were previously developed for other diseases and viral diseases, there is a possibility of side effects when used as a treatment for COVID-19. In the case of plasma therapy, plasma from recovered patients is continuously needed, and human monoclonal Antibody treatments have the disadvantages of taking longer to manufacture and making mass production difficult compared to compound-based treatments. Therefore, there is an urgent need to develop a highly safe and effective treatment to fundamentally solve the COVID-19 situation.
코로나 바이러스 감염은 바이러스 표면의 스파이크 단백질이 세포막과의 결합을 통하여 시작된다. 따라서, 스파이크 단백질이 세포막에 결합하는 과정을 억제하면, 바이러스의 세포 감염을 원천적으로 봉쇄할 수 있다. Coronavirus infection begins through the binding of the spike protein on the surface of the virus to the cell membrane. Therefore, by inhibiting the process of spike protein binding to the cell membrane, viral cell infection can be fundamentally blocked.
한편, 오배자(Galla rhois)는 옻나무과(Anacardiaceae)에 속하는 붉나무(Rhus javanica L.)의 잎에 오배자진딧물(Aphis chinensis J. Bell)이 자상(刺傷)을 주어생긴 벌레집을 말하는데, 우리나라 각지에 분포한다. 오배자의 형태를 보면, 외면은 회갈색으로 연한 털이 있고, 길이는 3~7cm, 폭 2~5cm, 두께 2mm 정도이며 단단하면서도 쉽게 부숴 진다. 속은 대개 비어 있거나 회백색의 죽은 벌레와 분비물이 남아 있을 때도 있고, 역겨운 냄새가 나기도 한다. 채집한 오배자는 햇볕에 말리거나 삶거나 쪄서 사용된다. 주성분으로는 피로가롤 탄닌(pyrogallol tannin)이 50~70% 함유되어 있으며, 몰식자산, 갈산(gallic acid) 등이 있다. 약효로는 수렴, 지사, 지혈제로 설사, 가래, 당뇨, 하혈, 빈혈 등에 이용한다(정보섭 외, 향약대사전, pp. 380~384, 영림사, 1998).Meanwhile, Galla rhois refers to an insect nest formed by a puncture wound by the gallbladder aphid ( Aphis chinensis J. Bell) on the leaves of Rhus javanica L., belonging to the Anacardiaceae family. It is distributed throughout Korea. . Looking at the shape of the gallbladder, the outer surface is gray-brown with light hairs, is 3 to 7 cm long, 2 to 5 cm wide, and 2 mm thick, and is hard but easily broken. The inside is usually empty or sometimes contains gray-white dead bugs and secretions, and sometimes has a disgusting odor. The collected gallnuts are dried in the sun, boiled, or steamed before use. The main ingredients include 50-70% pyrogallol tannin, gallic acid, and gallic acid. It is used as an astringent, antidiarrheal, and hemostatic agent for diarrhea, phlegm, diabetes, bleeding, and anemia (Jeong Bo-seop et al., Dictionary of Herbal Medicine, pp. 380-384, Younglimsa, 1998).
따라서, 본 발명은 숙주세포에 코로나 바이러스(SARS-CoV-2)를 감염 시, 오배자 30 내지 70% 에탄올 추출물, 더욱 바람직하게는 50% 에탄올 추출물이 숙주세포에 코로나 바이러스 감염(코로나19)를 효과적으로 억제하는 것을 확인하였다. 즉, 코로나 바이러스가 숙주세포에 감염되는 것을 차단하는 것을 확인하였다. 이는 오배자 30 내지 70% 에탄올 추출물, 더욱 바람직하게는 50% 에탄올 추출물이 스파이크 단백질의 세포막 결합을 차단하여 감염을 억제할 수 있음을 강력하게 보여주는 결과이다. 스파이크 단백질의 세포막 결합을 막아 감염을 억제하는 기전은 중화항체가 바이러스에 결합하여 세포 감염을 차단하는 것과 유사한 효과이므로 매우 유용한 치료제로 사용될 수 있다. 동일한 조건에서, 렘데시비르(바이러스 RNA 복제 억제)와 클로로퀸(바이러스 감염 후 세포 내 이동 억제)은 코로나 바이러스의 감염을 전혀 억제하지 못하였다.Therefore, the present invention provides that when infecting a host cell with a coronavirus (SARS-CoV-2), a 30 to 70% ethanol extract, more preferably a 50% ethanol extract, effectively infects the host cell with the coronavirus (COVID-19). Suppression was confirmed. In other words, it was confirmed that it blocks the coronavirus from infecting host cells. This is a result that strongly shows that 30 to 70% ethanol extract, and more preferably 50% ethanol extract, of the shipwreck can inhibit infection by blocking the binding of the spike protein to the cell membrane. The mechanism of inhibiting infection by blocking the binding of spike proteins to the cell membrane is similar to the effect of neutralizing antibodies blocking cell infection by binding to viruses, so it can be used as a very useful treatment. Under the same conditions, remdesivir (inhibits viral RNA replication) and chloroquine (inhibits intracellular movement after viral infection) did not inhibit coronavirus infection at all.
또한, 바이러스가 세포에 감염된 이후 오배자 추출물을 처리하였을 경우에도 클로로퀸보다 우수하며 렘데시비르와 유사한 감염억제 효과를 관찰하였다. 이러한 결과는 오배자 추출물이 바이러스의 세포 내 침투 이후에도 바이러스의 증식을 억제하는 것을 보여준다.In addition, even when the shipwreck extract was treated after the virus infected cells, an infection-inhibiting effect similar to that of remdesivir was observed, which was superior to chloroquine. These results show that the shipwreck extract inhibits the proliferation of the virus even after the virus penetrates the cells.
상기 결과를 통해 오배자 추출물은 코로나 바이러스(SARS-CoV-2) 감염 억제 효과는 물론, 세포 내 침투 후에도 코로나 바이러스(SARS-CoV-2)의 증식을 강력하게 억제할 수 있다.Based on the above results, the extract of Shipwort not only has the effect of suppressing coronavirus (SARS-CoV-2) infection, but can also strongly inhibit the proliferation of coronavirus (SARS-CoV-2) even after penetration into cells.
따라서, 본 발명은 오배자 추출물을 유효성분으로 포함하는 코로나 바이러스(SARS-CoV-2) 감염증에 대한 예방, 개선 또는 치료용 조성물을 제공하는데 그 목적이 있다. Accordingly, the purpose of the present invention is to provide a composition for preventing, improving, or treating coronavirus (SARS-CoV-2) infection, which contains an extract of Shipwort as an active ingredient.
본 발명의 목적은 오배자(Galla rhois) 추출물을 유효성분으로 포함하는 코로나 바이러스(SARS-CoV-2) 감염의 예방 또는 개선용 건강기능식품 조성물을 제공하는 것이다.The purpose of the present invention is to provide a health functional food composition for preventing or improving coronavirus (SARS-CoV-2) infection containing Galla rhois extract as an active ingredient.
또한, 본 발명의 다른 목적은 오배자(Galla rhois) 추출물을 유효성분으로 포함하는 코로나 바이러스(SARS-CoV-2) 감염의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.In addition, another object of the present invention is to provide a pharmaceutical composition for preventing or treating coronavirus (SARS-CoV-2) infection containing Galla rhois extract as an active ingredient.
또한, 오배자에서 분리된 penta-O-galloyl-β-D-glucose(PGG)를 유효성분으로 포함하는 코로나 바이러스(SARS-CoV-2) 감염의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.In addition, a pharmaceutical composition for preventing or treating coronavirus (SARS-CoV-2) infection containing penta-O-galloyl-β-D-glucose (PGG) isolated from gallbladder as an active ingredient is provided.
즉, 본 발명은 오배자 추출물 또는 이로부터 분리된 penta-O-galloyl-β-D-glucose(PGG)를 이용하여 코로나 바이러스(SARS-CoV-2) 감염에 대한 예방, 개선 또는 치료 효과를 확인하고, 이를 통해 오배자 추출물 또는 penta-O-galloyl-β-D-glucose(PGG)를 이용한 코로나 바이러스(SARS-CoV-2)를 예방, 개선 또는 치료할 수 있는 건강기능식품 또는 의약품으로 사용 가능한 조성물을 제조하는 것을 목적으로 한다.In other words, the present invention confirms the prevention, improvement, or treatment effect on coronavirus (SARS-CoV-2) infection using the extract of Starfish or penta-O-galloyl-β-D-glucose (PGG) isolated therefrom. Through this, a composition that can be used as a health functional food or medicine to prevent, improve, or treat coronavirus (SARS-CoV-2) using gallnut extract or penta-O-galloyl-β-D-glucose (PGG) is manufactured. The purpose is to
상기 과제를 해결하기 위하여, 본 발명은 오배자 추출물을 유효성분으로 포함하는, 코로나 바이러스(SARS-CoV-2) 감염의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In order to solve the above problems, the present invention provides a health functional food composition for preventing or improving coronavirus (SARS-CoV-2) infection, which contains an extract of Shipwort as an active ingredient.
본 발명의 일 실시예에 있어서, 본 발명의 ‘오배자 추출물’은 물, C1 내지 C4의 알코올, 에틸아세테이트, 클로로포름 및 헥산 중에서 선택된 적어도 어느 하나의 용매로 추출된 것일 수 있고, 바람직하게는 30 내지 70% 에탄올을 사용하여 추출된 것일 수 있으며, 더욱 바람직하게는 50% 에탄올을 사용하여 추출된 것일 수 있으나, 이에 한정되는 것은 아니다.In one embodiment of the present invention, the 'Shipberry extract' of the present invention is water, C 1 to It may be extracted with at least one solvent selected from C 4 alcohol, ethyl acetate, chloroform and hexane, preferably using 30 to 70% ethanol, more preferably 50% ethanol. It may be extracted using, but is not limited to this.
본 발명의 일 실시예에 있어서, 본 발명의 ‘코로나 바이러스’는 베타-코로나 바이러스일 수 있으나, 이에 한정되는 것은 아니다.In one embodiment of the present invention, the ‘coronavirus’ of the present invention may be a beta-coronavirus, but is not limited thereto.
본 발명의 일 실시예에 있어서, 본 발명의 ‘오배자 추출물’은 코로나 바이러스(SARS-CoV-2)에 대한 플라크 감소 효과를 가지는 것일 수 있으나, 이에 한정되는 것은 아니다.In one embodiment of the present invention, the ‘Shipberry extract’ of the present invention may have a plaque reducing effect on coronavirus (SARS-CoV-2), but is not limited thereto.
본 발명의 일 실시예에 있어서, 본 발명의 ‘오배자 추출물’은 코로나 바이러스(SARS-CoV-2) 복제를 억제시키는 것일 수 있으나, 이에 한정되는 것은 아니다.In one embodiment of the present invention, the ‘Shipberry extract’ of the present invention may inhibit coronavirus (SARS-CoV-2) replication, but is not limited thereto.
본 발명의 일 실시예에 있어서, 본 발명의 ‘오배자 추출물’은 penta-O-galloyl-β-D-glucose(PGG) 성분을 포함하는 것일 수 있으나, 이에 한정되는 것은 아니다.In one embodiment of the present invention, the ‘Shipberry extract’ of the present invention may contain a penta-O-galloyl-β-D-glucose (PGG) component, but is not limited thereto.
본 발명의 일 실시예에 있어서, 본 발명의 ‘오배자 추출물’은 코로나 바이러스로 인한 발열을 억제하는 효과를 가지는 것일 수 있으나, 이에 한정되는 것은 아니다.In one embodiment of the present invention, the ‘Shipberry extract’ of the present invention may have the effect of suppressing fever caused by coronavirus, but is not limited thereto.
본 발명의 일 실시예에 있어서, 본 발명의 ‘조성물’은 코로나 바이러스 스파이크 단백질의 세포막 결합을 차단하여 감염을 억제하는 것일 수 있으나, 이에 한정되는 것은 아니다.In one embodiment of the present invention, the ‘composition’ of the present invention may inhibit infection by blocking the binding of the coronavirus spike protein to the cell membrane, but is not limited thereto.
또한, 본 발명은 오배자 추출물을 유효성분으로 포함하는 코로나 바이러스(SARS-CoV-2) 감염의 예방 또는 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating coronavirus (SARS-CoV-2) infection comprising an extract of Shipwort as an active ingredient.
또한, 본 발명은 오배자에서 분리된 penta-O-galloyl-β-D-glucose(PGG)를 유효성분으로 포함하는 코로나 바이러스(SARS-CoV-2) 감염의 예방 또는 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating coronavirus (SARS-CoV-2) infection containing penta-O-galloyl-β-D-glucose (PGG) isolated from gallbladder as an active ingredient. .
2002년 유행한 사스(SARS), 2012년 유행한 메르스(MERS), 그리고 2020년 유행한 코로나-19(COVID-19)까지 다양한 코로나 바이러스에 의하여 전세계적으로 많은 사람이 사망하였다. 또한, 코로나 바이러스는 RNA 바이러스의 특성상 돌연변이가 쉽게 일어나기 쉽기 때문에 변형된 코로나 바이러스가 발생될 확률이 높다. 따라서 본 발명에 따른, 천연물인 오배자 추출물을 사용하여 숙주세포에 코로나 바이러스(SARS-CoV-2)를 감염 시, 오배자 30 내지 70% 에탄올 추출물, 더욱 바람직하게는 50% 에탄올 추출물이 숙주세포에 코로나 바이러스(SARS-CoV-2) 감염을 효과적으로 억제하는 것 확인하였다. 즉, 코로나 바이러스가 숙주세포에 감염되는 것을 차단하는 것을 확인하였다. 이는 오배자 30 내지 70% 에탄올 추출물, 더욱 바람직하게는50% 에탄올 추출물이 스파이크 단백질의 세포막 결합을 차단하여 감염을 억제할 수 있음을 강력하게 보여주는 결과이다. 스파이크 단백질의 세포막 결합을 막아 감염을 억제하는 기전은 중화항체가 바이러스에 결합하여 세포 감염을 차단하는 것과 유사한 효과이므로 매우 유용한 치료제로 사용될 수 있다. 동일한 조건에서, 렘데시비르(바이러스 RNA 복제 억제)와 클로로퀸(바이러스 감염 후 세포 내 이동 억제)은 코로나 바이러스의 감염을 전혀 억제하지 못하였다. 또한, 바이러스가 세포에 감염된 이후 오배자 추출물을 처리하였을 경우에도 클로로퀸보다 우수하며 렘데시비르와 유사한 감염억제 효과를 관찰하였다. 이러한 결과는 오배자 추출물이 바이러스의 세포 내 침투 이후에도 바이러스의 증식을 억제하는 것을 보여준다. 상기 결과를 통해 오배자 추출물은 코로나 바이러스(SARS-CoV-2) 감염 억제 효과는 물론, 세포 내 침투 후에도 코로나 바이러스(SARS-CoV-2)의 증식을 강력하게 억제할 수 있음을 확인하여 본 발명을 완성하였다.Many people around the world have died from various coronaviruses, including SARS in 2002, MERS in 2012, and COVID-19 in 2020. In addition, coronaviruses are prone to mutations due to the nature of RNA viruses, so there is a high probability that modified coronaviruses will occur. Therefore, when infecting a host cell with coronavirus (SARS-CoV-2) using the ship extract, which is a natural product according to the present invention, 30 to 70% ethanol extract, more preferably 50% ethanol extract, is used to infect the host cell with the coronavirus. It was confirmed that it effectively inhibits virus (SARS-CoV-2) infection. In other words, it was confirmed that it blocks the coronavirus from infecting host cells. This is a result that strongly shows that 30 to 70% ethanol extract, and more preferably 50% ethanol extract, of the shipwreck can inhibit infection by blocking the binding of the spike protein to the cell membrane. The mechanism of inhibiting infection by blocking the binding of spike proteins to the cell membrane is similar to the effect of neutralizing antibodies blocking cell infection by binding to viruses, so it can be used as a very useful treatment. Under the same conditions, remdesivir (inhibits viral RNA replication) and chloroquine (inhibits intracellular movement after viral infection) did not inhibit coronavirus infection at all. In addition, even when the shipwreck extract was treated after the virus infected cells, an infection-inhibiting effect similar to that of remdesivir was observed, which was superior to chloroquine. These results show that the shipwreck extract inhibits the proliferation of the virus even after the virus penetrates the cells. Through the above results, it was confirmed that the extract of Shipwort not only has the effect of inhibiting coronavirus (SARS-CoV-2) infection, but also can strongly inhibit the proliferation of coronavirus (SARS-CoV-2) even after penetration into cells, thereby supporting the present invention. Completed.
도 1은 본 발명의 오배자 추출물이 코로나 바이러스(SARS-CoV-2)의 세포 감염을 억제함으로써 항바이러스 효능을 나타낸 도이다.
도 2는 본 발명의 오배자 추출물을 이용하여 플라크 감소 분석을 실험하여 결과를 나타낸 도이다.
도 3은 본 발명의 오배자 추출물을 이용하여 vrial RNA 억제를 실험하여 결과를 나타낸 도이다.
도 4는 본 발명의 오배자 성분을 이용하여 플라크 감소 분석을 실험하여 결과를 나타낸 도이다.
도 5는 본 발명의 오배자 성분인 PGG와 SARS-CoV-2 spike RBD의 molecular docking을 분석하여 나타낸 도이다.
도 6은 체온 상승 유발물질(LPS)에 의한 발열에 대한 오배자 추출물 및 양성대조군(indomethacin)의 해열 효과를 나타낸 도이다.Figure 1 is a diagram showing the antiviral efficacy of the shipwreck extract of the present invention by inhibiting cell infection of coronavirus (SARS-CoV-2).
Figure 2 is a diagram showing the results of a plaque reduction analysis experiment using the shipwreck extract of the present invention.
Figure 3 is a diagram showing the results of an experiment for vrial RNA inhibition using the shipwreck extract of the present invention.
Figure 4 is a diagram showing the results of a plaque reduction analysis experiment using the shipwreck component of the present invention.
Figure 5 is a diagram showing molecular docking analysis of PGG, which is a starfish component of the present invention, and SARS-CoV-2 spike RBD.
Figure 6 is a diagram showing the antipyretic effect of the gallbladder extract and positive control group (indomethacin) on fever caused by body temperature increase substance (LPS).
이하, 첨부된 도면을 참조하여 본 발명의 실시예로 본 발명을 상세히 설명하기로 한다. 다만, 하기 실시예는 본 발명에 대한 예시로 제시되는 것으로, 당업자에게 주지 저명한 기술 또는 구성에 대한 구체적인 설명이 본 발명의 요지를 불필요하게 흐릴 수 있다고 판단되는 경우에는 그 상세한 설명을 생략할 수 있고, 이에 의해 본 발명이 제한되지는 않는다. 본 발명은 후술하는 특허 청구범위의 기재 및 그로부터 해석되는 균등 범주 내에서 다양한 변형 및 응용이 가능하다.Hereinafter, the present invention will be described in detail through embodiments of the present invention with reference to the attached drawings. However, the following examples are provided as examples of the present invention, and if it is judged that a detailed description of a technology or configuration well known to those skilled in the art may unnecessarily obscure the gist of the present invention, the detailed description may be omitted. , the present invention is not limited thereby. The present invention is capable of various modifications and applications within the description of the patent claims described below and the scope of equivalents interpreted therefrom.
또한, 본 명세서에서 사용되는 용어(terminology)들은 본 발명의 바람직한 실시예를 적절히 표현하기 위해 사용된 용어들로서, 이는 사용자, 운용자의 의도 또는 본 발명이 속하는 분야의 관례 등에 따라 달라질 수 있다. 따라서, 본 용어들에 대한 정의는 본 명세서 전반에 걸친 내용을 토대로 내려져야 할 것이다. 명세서 전체에서, 어떤 부분이 어떤 구성요소를 "포함"한다고 할 때, 이는 특별히 반대되는 기재가 없는 한 다른 구성요소를 제외하는 것이 아니라 다른 구성 요소를 더 포함할 수 있는 것을 의미한다.In addition, the terminology used in this specification is a term used to appropriately express preferred embodiments of the present invention, and may vary depending on the intention of the user or operator or the customs of the field to which the present invention belongs. Therefore, definitions of these terms should be made based on the content throughout this specification. Throughout the specification, when a part is said to “include” a certain element, this means that it may further include other elements rather than excluding other elements, unless specifically stated to the contrary.
본 명세서 전체에 걸쳐, 특정 물질의 농도를 나타내기 위하여 사용되는 '%'는 별도의 언급이 없는 경우, 고체/고체는(w/w) %, 고체/액체는(w/v) %, 그리고 액체/액체는(v/v) %이다.Throughout this specification, '%' used to indicate the concentration of a specific substance means (w/w) % for solid/solid, (w/v) % for solid/liquid, and Liquid/liquid is (v/v) %.
본 발명에서 사용되는 모든 기술용어는, 달리 정의되지 않는 이상, 본 발명의 관련 분야에서 통상의 당업자가 일반적으로 이해하는 바와 같은 의미로 사용된다. 또한 본 명세서에는 바람직한 방법이나 시료가 기재되나, 이와 유사하거나 동등한 것들도 본 발명의 범주에 포함된다. 본 명세서에 참고문헌으로 기재되는 모든 간행물의 내용은 본 발명에 도입된다.All technical terms used in the present invention, unless otherwise defined, are used with the same meaning as commonly understood by a person skilled in the art in the field related to the present invention. In addition, preferred methods and samples are described in this specification, but similar or equivalent methods are also included in the scope of the present invention. The contents of all publications incorporated by reference herein are hereby incorporated by reference.
일 측면에서, 본 발명은 오배자 추출물을 유효성분으로 포함하는 코로나 바이러스(SARS-CoV-2) 감염의 예방 또는 개선용 건강기능식품 조성물을 제공하는 것을 목적으로 한다.In one aspect, the purpose of the present invention is to provide a health functional food composition for preventing or improving coronavirus (SARS-CoV-2) infection, which contains an extract of Chinese galleon chinensis as an active ingredient.
본 발명에 따른 추출물은 당업계에 공지된 추출 및 분리방법을 사용하여 천연 오배자로부터 추출 및 분리하여 수득한 것을 사용할 수 있으며, 본 발명에서 정의된 “추출물”은 적절한 용매를 이용하여 오배자로부터 추출한 것이며, 예를 들어, 조추출물, 극성용매 가용 추출물 또는 비극성용매 가용 추출물을 모두 포함한다. 상기 오배자로부터 추출물을 추출하기 위한 적절한 용매로는 약학적으로 허용되는 유기용매라면 어느 것을 사용해도 무방하며, 물 또는 유기용매를 사용할 수 있으며, 이에 제한되지는 않으나, 예를 들어, 정제수, 메탄올(methanol), 에탄올(ethanol), 프로판올(propanol), 이소프로판올(isopropanol), 부탄올(butanol) 등을 포함하는 탄소수 1 내지 4의 알코올, 아세톤(acetone), 에테르(ether), 벤젠(benzene), 클로로포름(chloroform), 에틸아세테이트(ethyl acetate), 메틸렌클로라이드(methylene chloride), 헥산(hexane) 및 시클로헥산(cyclohexane) 등의 각종 용매를 단독으로 혹은 혼합하여 사용할 수 있고, 바람직하게는 에탄올 30 내지 70%를 용매로 사용하였으며, 더욱 바람직하게는 에탄올 50%를 용매로 사용하였다. 추출 방법으로는 열수추출법, 냉침추출법, 환류냉각추출법, 용매추출법, 수증기증류법, 초음파추출법, 용출법, 압착법 등의 방법 중 어느 하나를 선택하여 사용할 수 있다. 또한, 목적하는 추출물은 추가로 통상의 분획 공정을 수행할 수도 있으며, 통상의 정제 방법을 이용하여 정제될 수도 있다.The extract according to the present invention can be obtained by extraction and separation from natural shipwreck using extraction and separation methods known in the art, and “extract” as defined in the present invention is extracted from shipwreck using an appropriate solvent. , for example, includes all crude extracts, polar solvent-soluble extracts, or non-polar solvent-soluble extracts. A suitable solvent for extracting the extract from the above shipbuilding extract may be any pharmaceutically acceptable organic solvent, and water or an organic solvent may be used, but is not limited thereto, for example, purified water, methanol ( Alcohols with 1 to 4 carbon atoms including methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene, chloroform ( Various solvents such as chloroform, ethyl acetate, methylene chloride, hexane, and cyclohexane can be used individually or in combination, preferably 30 to 70% ethanol. It was used as a solvent, and more preferably 50% ethanol was used as a solvent. As an extraction method, any one of the following methods can be selected and used: hot water extraction, cold needle extraction, reflux cooling extraction, solvent extraction, steam distillation, ultrasonic extraction, elution, and compression. In addition, the desired extract may be further subjected to a conventional fractionation process or may be purified using a conventional purification method.
본 발명의 추출물의 제조방법에는 제한이 없으며, 공지되어있는 어떠한 방법도 이용될 수 있다. 예를 들면, 본 발명의 조성물에 포함되는 추출물은 상기한 열수 추출 또는 용매 추출법으로 추출된 1차 추출물을, 감압 증류 및 동결건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말상태로 제조할 수 있다. 또한 상기 1차 추출물을 실리카 겔 컬럼 크로마토그래피(silica gel column chromatography), 박층 크로마토그래피(thin layer chromatography), 고성능 액체 크로마토그래피(high performance liquid chromatography) 등과 같은 다양한 크로마토그래피를 이용하여 추가로 정제된 분획을 얻을 수도 있다. 따라서 본 발명에 있어서 추출물은 추출, 분획 또는 정제의 각 단계에서 얻어지는 모든 추출액, 분리된 화합물, 분획 및 정제물, 그들의 희석액, 농축액 또는 건조물을 모두 포함하는 개념이다.There is no limitation to the method for producing the extract of the present invention, and any known method can be used. For example, the extract included in the composition of the present invention can be prepared in powder form from the primary extract extracted by the above-mentioned hot water extraction or solvent extraction method by additional processes such as reduced pressure distillation and freeze-drying or spray drying. In addition, the primary extract was further purified into fractions using various chromatographies such as silica gel column chromatography, thin layer chromatography, high performance liquid chromatography, etc. You can also get Therefore, in the present invention, extract is a concept that includes all extracts, separated compounds, fractions and purifications, and their dilutions, concentrates or dried products obtained at each stage of extraction, fractionation or purification.
본 발명의 오배자 추출물을 건강기능식품 조성물로 사용하는 경우, 상기 오배자 추출물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용할 수 있고, 통상의 방법에 따라 적절하게 사용할 수 있다. 상기 조성물은 유효성분 이외에 식품학적으로 허용가능한 식품보조첨가제를 포함할 수 있으며, 유효성분의 혼합량은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다.When using the shipwreck extract of the present invention as a health functional food composition, the shipwreck extract can be added as is or used together with other foods or food ingredients, and can be used appropriately according to conventional methods. In addition to the active ingredients, the composition may contain food additives acceptable to the food industry, and the mixing amount of the active ingredients can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment).
본 발명에서 사용되는 용어 "식품보조첨가제"란 식품에 보조적으로 첨가될 수 있는 구성요소를 의미하며, 각 제형의 건강기능식품을 제조하는데 첨가되는 것으로서 당업자가 적절히 선택하여 사용할 수 있다. 식품보조첨가제의 예로는 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 충진제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등이 포함되지만, 상기 예들에 의해 본 발명의 식품보조첨가제의 종류가 제한되는 것은 아니다.The term "food supplement" used in the present invention refers to a component that can be added as an auxiliary food additive, and can be appropriately selected and used by a person skilled in the art as it is added to manufacture each type of health functional food. Examples of food supplements include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, and protective colloidal thickeners. , pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc., but the types of food supplements of the present invention are not limited to the above examples.
본 발명의 식품 조성물에는 건강기능식품이 포함될 수 있다. 본 발명에서 사용되는 용어 "건강기능식품"이란 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 정제, 캅셀, 분말, 과립, 액상 및 환 등의 형태로 제조 및 가공한 식품을 말한다. 여기서 '기능성'이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 건강기능식품은 통상의 기술분야에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조시에는 통상의 기술분야에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 상기 건강기능식품의 제형 또한 건강기능식품으로 인정되는 제형이면 제한없이 제조될 수 있다. 본 발명의 식품용 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 본 발명의 건강기능식품은 앙염증 효과를 증진시키기 위한 보조제로 섭취가 가능하다.The food composition of the present invention may include health functional foods. The term “health functional food” used in the present invention refers to food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and pills using raw materials or ingredients with functional properties useful to the human body. Here, ‘functionality’ means controlling nutrients for the structure and function of the human body or obtaining useful effects for health purposes, such as physiological effects. The health functional food of the present invention can be manufactured by methods commonly used in the field of technology, and can be manufactured by adding raw materials and components commonly added in the field of technology. Additionally, the formulation of the health functional food can also be manufactured without limitation as long as it is a formulation recognized as a health functional food. The food composition of the present invention can be manufactured in various types of formulations, and unlike general drugs, it is made from food as a raw material and has the advantage of not having side effects that may occur when taking the drug for a long period of time, and is excellent in portability, so the present invention Health functional foods can be consumed as supplements to enhance the anti-inflammatory effect.
또한, 본 발명의 조성물이 사용될 수 있는 건강식품의 종류에는 제한이 없다. 아울러 본 발명의 오배자 추출물을 유효성분으로 포함하는 조성물은 당업자의 선택에 따라 건강기능식품에 함유될 수 있는 적절한 기타 보조 성분과 공지의 첨가제를 혼합하여 제조할 수 있다. 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림 류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 본 발명에 따른 추출물을 주성분으로 하여 제조한 즙, 차, 젤리 및 주스 등에 첨가하여 제조할 수 있다.Additionally, there is no limitation to the types of health foods in which the composition of the present invention can be used. In addition, a composition containing the shipwreck extract of the present invention as an active ingredient can be prepared by mixing known additives with other appropriate auxiliary ingredients that can be contained in health functional foods according to the selection of a person skilled in the art. Examples of foods that can be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and There are vitamin complexes, etc., and they can be manufactured by adding them to juices, teas, jellies, juices, etc. prepared using the extract according to the present invention as a main ingredient.
이하 본 발명의 오배자 추출물을 유효성분으로 포함하는, 코로나 바이러스 감염의 예방 또는 개선용 건강기능식품의 제조예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, an example of manufacturing a health functional food for preventing or improving coronavirus infection containing the ship extract of the present invention as an active ingredient will be described. However, the present invention is not intended to be limited, but merely explained in detail.
<제조예 1><Manufacturing Example 1>
오배자 추출물 200 ㎎Shipwreck extract 200 mg
비타민 A 아세테이트 70 ㎍Vitamin A acetate 70 μg
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B 1 0.13 ㎎Vitamin B 1 0.13 mg
비타민 B 2 0.15 ㎎Vitamin B 2 0.15 mg
비타민 B 6 0.5㎎Vitamin B 6 0.5mg
비타민 B 12 0.2 ㎍Vitamin B 12 0.2 ㎍
비타민 C 10 ㎎Vitamin C 10 mg
비오틴10 ㎍Biotin 10 ㎍
니코틴산아미드 1.7 ㎎Nicotinamide 1.7 mg
엽산 50 ㎍Folic acid 50 μg
판토텐산 칼슘 0.5 ㎎Calcium pantothenate 0.5 mg
황산제1철 1.75 ㎎Ferrous sulfate 1.75 mg
산화아연 0.82 ㎎Zinc oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Monobasic Potassium Phosphate 15 mg
제2인산칼슘 55 ㎎Dibasic calcium phosphate 55 mg
구연산칼륨 90 ㎎Potassium citrate 90 mg
탄산칼슘 100 ㎎Calcium carbonate 100 mg
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
일 측면에서, 본 발명은 오배자 추출물을 유효성분으로 포함하는 코로나 바이러스(SARS-CoV-2) 감염의 예방 또는 치료용 약학적 조성물 또는 오배자에서 분리된 penta-O-galloyl-β-D-glucose(PGG)를 유효성분으로 포함하는 코로나 바이러스(SARS-CoV-2) 감염의 예방 또는 치료용 약학적 조성물을 제공하는 것을 목적으로 한다.In one aspect, the present invention provides a pharmaceutical composition for the prevention or treatment of coronavirus (SARS-CoV-2) infection comprising an extract of the shipwreck as an active ingredient or penta-O-galloyl-β-D-glucose ( The purpose is to provide a pharmaceutical composition for preventing or treating coronavirus (SARS-CoV-2) infection containing PGG) as an active ingredient.
본 발명에서 사용된 용어 "치료"란 본 발명의 조성물의 투여로 코로나 바이러스 감염, 바람직하게는 코로나 바이러스(SARS-CoV-2) 감염의 증세를 호전시키거나 이롭게 변경하는 모든 행위를 의미한다. 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자라면, 대한의학협회 등에서 제시된 자료를 참조하여 본 발명의 조성물이 효과가 있는 질환의 정확한 기준을 알고, 개선, 향상 및 치료된 정도를 판단할 수 있을 것이다.The term "treatment" used in the present invention refers to any action that improves or beneficially changes the symptoms of coronavirus infection, preferably coronavirus (SARS-CoV-2) infection, by administering the composition of the present invention. Anyone skilled in the art to which the present invention pertains can refer to data presented by the Korean Medical Association, etc. to know the exact criteria for diseases for which the composition of the present invention is effective and determine the degree of improvement, improvement, and treatment. There will be.
일 구현예에서, 상기 약학 조성물은 경구형 제형, 외용제, 좌제, 멸균 주사용액 및 분무제를 포함하는 군으로부터 선택되는 하나 이상의 제형일 수 있으며, 주사 제형이 더욱 바람직하다.In one embodiment, the pharmaceutical composition may be one or more formulations selected from the group including oral formulations, topical formulations, suppositories, sterile injectable solutions, and sprays, with an injectable formulation being more preferable.
본 발명에서, 용어 "예방"이란 본 발명에 따른 약학적 조성물의 투여에 의해 코로나 바이러스 감염, 바람직하게는 코로나 바이러스(SARS-CoV-2) 감염의 발생, 확산 및 재발을 억제 또는 지연시키는 모든 행위를 의미한다.In the present invention, the term "prevention" refers to any act of suppressing or delaying the occurrence, spread, and recurrence of a coronavirus infection, preferably a coronavirus (SARS-CoV-2) infection, by administering the pharmaceutical composition according to the present invention. means.
본 발명에서 유효성분과 결합하여 사용된 "치료학적으로 유효한 양"이란 용어는 대상 질환을 예방 또는 치료하는데 유효한 조성물의 약학적으로 허용가능한 염의 양을 의미하며, 본 발명의 조성물의 치료적으로 유효한 양은 여러 요소, 예를 들면 투여방법, 목적부위, 환자의 상태 등에 따라 달라질 수 있다. 따라서, 인체에 사용 시 투여량은 안전성 및 효율성을 함께 고려하여 적정량으로 결정되어야 한다. 동물실험을 통해 결정한 유효량으로부터 인간에 사용되는 양을 추정하는 것도 가능하다. 유효한 양의 결정시 고려할 이러한 사항은, 예를 들면 Hardman and Limbird, eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed. (2001), Pergamon Press; 및 E.W. Martin ed., Remington's Pharmaceutical Sciences, 18th ed. (1990), Mack Publishing Co.에 기술되어있다.The term "therapeutically effective amount" used in combination with an active ingredient in the present invention refers to the amount of a pharmaceutically acceptable salt of the composition effective in preventing or treating the target disease, and the therapeutically effective amount of the composition of the present invention is It may vary depending on several factors, such as administration method, target site, and patient condition. Therefore, when used in the human body, the dosage must be determined as appropriate by considering both safety and efficiency. It is also possible to estimate the amount used in humans from the effective amount determined through animal testing. These considerations in determining an effective amount are discussed, for example, in Hardman and Limbird, eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed. (2001), Pergamon Press; and E.W. Martin ed., Remington's Pharmaceutical Sciences, 18th ed. (1990), Mack Publishing Co.
본 발명의 약학적 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명에서 사용되는 용어, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며 부작용을 일으키지 않을 정도의 양을 의미하며, 유효용량 수준은 환자의 건강상태, 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 배합 또는 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고, 종래의 치료제와 순차적으로 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여, 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. As used in the present invention, the term "pharmaceutically effective amount" refers to an amount that is sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects, and the effective dose level is determined by the patient's Factors including health status, type and severity of disease, activity of drug, sensitivity to drug, method of administration, time of administration, route of administration and excretion rate, duration of treatment, drugs combined or used simultaneously, and other factors well known in the field of medicine. It can be decided depending on The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve maximum effect with the minimum amount without side effects, and this can be easily determined by a person skilled in the art.
본 발명의 약학 조성물은 약제학적으로 허용 가능한 첨가제를 더 포함할 수 있으며, 이때 약제학적으로 허용 가능한 첨가제로는 전분, 젤라틴화 전분, 미결정셀룰로오스, 유당, 포비돈, 콜로이달실리콘디옥사이드, 인산수소칼슘, 락토스, 만니톨, 엿, 아라비아고무, 전호화전분, 옥수수전분, 분말셀룰로오스, 히드록시프로필셀룰로오스, 오파드라이, 전분글리콜산나트륨, 카르나우바 납, 합성규산알루미늄, 스테아린산, 스테아린산마그네슘, 스테아린산알루미늄, 스테아린산칼슘, 백당, 덱스트로스, 소르비톨 및 탈크 등이 사용될 수 있다. 본 발명에 따른 약제학적으로 허용 가능한 첨가제는 상기 조성물에 대해 0.1 중량부 내지 90 중량부 포함되는 것이 바람직하나, 이에 한정되는 것은 아니다.The pharmaceutical composition of the present invention may further include pharmaceutically acceptable additives. In this case, the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate, Lactose, mannitol, taffy, gum arabic, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, Opadry, sodium starch glycolate, lead carnauba, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, stearic acid. Calcium, white sugar, dextrose, sorbitol, and talc may be used. 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, but is not limited thereto.
본 발명의 조성물은 또한 생물학적 제제에 통상적으로 사용되는 담체, 희석제, 부형제 또는 둘 이상의 이들의 조합을 포함할 수 있다. 약제학적으로 허용 가능한 담체는 조성물을 생체 내 전달에 적합한 것이면 특별히 제한되지 않으며, 예를 들면, Merck Index, 13th ed., Merck & Co. Inc. 에 기재된 화합물, 식염수, 멸균수, 링거액, 완충 식염수, 덱스트로스 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 이용할 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 주이용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. 더 나아가 당 분야의 적정한 방법으로 또는 Remington's Pharmaceutical Science(Mack Publishing Company, Easton PA, 18th, 1990)에 개시되어있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.The composition of the present invention may also include carriers, diluents, excipients, or combinations of two or more commonly used in biological products. Pharmaceutically acceptable carriers are not particularly limited as long as they are suitable for in vivo delivery of the composition, for example, Merck Index, 13th ed., Merck & Co. Inc. The compounds described in, saline solution, sterilized water, Ringer's solution, buffered saline solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these ingredients can be mixed and used, and if necessary, other ingredients such as antioxidants, buffers, and bacteriostatic agents. Normal additives can be added. In addition, diluents, dispersants, surfactants, binders, and lubricants can be additionally added to formulate dosage forms such as aqueous solutions, suspensions, emulsions, etc., into pills, capsules, granules, or tablets. Furthermore, it can be preferably formulated according to each disease or ingredient using an appropriate method in the art or a method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA, 18th, 1990).
본 발명의 조성물은 목적하는 방법에 따라 비 경구 투여(예를 들어 정맥 내, 피하, 복강 내 또는 국소에 주사 제형으로 적용)하거나 경구 투여할 수 있으며, 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설률 및 질환의 중증도 등에 따라 그 범위가 다양하다. 본 발명에 따른 조성물의 일일 투여량은 0.0001 ~ 10 ㎎/㎖이며, 바람직하게는 0.0001 ~ 5 ㎎/㎖이며, 하루 일 회 내지 수회에 나누어 투여하는 것이 더욱 바람직하다. The composition of the present invention can be administered parenterally (e.g., applied intravenously, subcutaneously, intraperitoneally, or topically as an injection formulation) or orally depending on the desired method, and the dosage is determined by the patient's weight, age, gender, The range varies depending on health status, diet, administration time, administration method, excretion rate, and severity of disease. The daily dosage of the composition according to the present invention is 0.0001 to 10 mg/ml, preferably 0.0001 to 5 mg/ml, and it is more preferable to administer it once or several times a day.
본 발명의 조성물의 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데, 통상적으로 사용되는 단순 희석제인 물, 액체 파라핀 이외에 다양한 부형제, 예컨대 습윤제, 감미제, 방향제, 보존제 등이 함께 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성 용제, 현탁제, 유제, 동결건조 제제, 좌제 등이 포함된다.Liquid preparations for oral administration of the composition of the present invention include suspensions, oral solutions, emulsions, syrups, etc., and in addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives are used. etc. may be included together. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, etc.
또한, 본 발명의 약학적 조성물은 기존의 코로나 바이러스 감염 치료용 조성물과 함께 투여함으로써, 코로나 바이러스 감염 치료 효과를 증가시킬 수 있다. 이때 병용 투여는 기존의 코로나 바이러스 감염 치료용 조성물과 동시에 또는 순차적으로 이루어질 수 있다.In addition, the pharmaceutical composition of the present invention can increase the effectiveness of treating coronavirus infection by administering it together with an existing composition for treating coronavirus infection. At this time, combined administration can be carried out simultaneously or sequentially with the existing composition for treating coronavirus infection.
본 발명의 오배자 추출물의 오배자(Galla rhois)는 한방에서 예로부터 널리 사용된 약재로 수렴, 지사, 지혈제로 설사, 가래, 당뇨, 하혈, 빈혈 등에 사용한다. 즉, 건강기능식품, 식품 또는 약학적 조성물로 사용할 경우에 일반적인 합성 화합물에 비하여 부작용이 덜할 수 있으므로, 안전하게 건강기능식품, 식품 또는 약학적 조성물에 포함되어 유용하게 사용될 수 있다. Galla rhois , the galla rhois extract of the present invention, is a medicinal herb widely used in oriental medicine since ancient times and is used as an astringent, antidiarrheal, and hemostatic agent for diarrhea, phlegm, diabetes, bleeding, and anemia. In other words, when used as a health functional food, food, or pharmaceutical composition, side effects may be less than those of general synthetic compounds, so it can be safely included in a health functional food, food, or pharmaceutical composition and usefully used.
하기의 실시예를 통하여 본 발명을 보다 상세하게 설명한다. 그러나 하기 실시예는 본 발명의 내용을 구체화하기 위한 것일 뿐 이에 의해 본 발명이 한정되는 것은 아니다.The present invention will be described in more detail through the following examples. However, the following examples are only for illustrating the content of the present invention and are not intended to limit the present invention.
<준비예 1> 실험의 재료 준비<Preparation Example 1> Preparation of materials for experiment
DMEM(-/-), Overlay media(0.6% agarose in DMEM), 12 well plate, Vero E6, 1x PBS(Cell culture grade)을 사용하여 하기의 실험방법에 의해 실험을 진행하였다.The experiment was conducted using DMEM (-/-), Overlay media (0.6% agarose in DMEM), 12 well plate, Vero E6, and 1x PBS (Cell culture grade) using the following experimental method.
<준비예 2> 오배자 추출물의 제조방법<Preparation Example 2> Manufacturing method of gallbladder extract
오배자(Galla rhois)의 잎은 서울의 BioKorea Co. LTd(Seoul)에서 구입하였고, 바우처 표본(BMRI-RG-1602)은 한국 용인 경희대학교 바이오메디컬연구센터에 기탁하였다. 건조된 샘플(20 kg)을 80±2℃에서 6시간 동안 50% 에탄올로 추출한 다음 여과하였다. 그 후, 회전 증발기를 사용하여 농축시키고 동결건조하였다. 최종 생성물 수율은 오배자 11.59 kg이었다. 오배자 추출물은 사용전까지 4 ℃에서 보관하였다. 여기에서 상기 에탄올 50% 오배자 추출물은 물, 메탄올 10%, 메탄올 30%, 메탄올 50%, 메탄올 70%, 메탄올 90%, 에탄올 10%, 에탄올 30%, 에탄올 50%, 에탄올 70%, 에탄올 90% 추출물을 이용한 예비실험에서의 최적화된 농도로 하기 실험에서는 에탄올 50% 오배자 추출물을 이용하여 실험을 진행하였다.The leaves of Galla rhois were purchased from BioKorea Co., Seoul. It was purchased from LTd (Seoul), and the voucher specimen (BMRI-RG-1602) was deposited at the Biomedical Research Center of Kyunghee University, Yongin, Korea. The dried sample (20 kg) was extracted with 50% ethanol for 6 hours at 80 ± 2°C and then filtered. Afterwards, it was concentrated using a rotary evaporator and lyophilized. The final product yield was 11.59 kg of gallbladder. The shipwreck extract was stored at 4°C until use. Here, the ethanol 50% shipwreck extract is water, 10% methanol, 30% methanol, 50% methanol, 70% methanol, 90% methanol, 10% ethanol, 30% ethanol, 50% ethanol, 70% ethanol, 90% ethanol. With the optimized concentration in the preliminary experiment using the extract, the following experiment was conducted using 50% ethanol extract of Shipwort extract.
<실시예 1> 실험방법<Example 1> Experimental method
① Vero E6 cells을 12 well plate에 3.0 x 105 cells/well로 seeding하고, ② 37℃, 5% CO2 인큐베이터에서 배양하였다. ③ 상등액을 제거하고, 1x PBS로 2번 wash 단계를 진행하였다. ④ 오배자 추출물(37℃, 5% CO2 인큐베이터, 1시간) 및 바이러스 흡착(virus adsorption) (50 pfu/well, shake/10 min)을 동시에 진행하고, ⑤ 상등액을 제거하고, add 1.5 mL overlay media, ⑥ 3일(72시간) 뒤에 결과를 확인하였다.① Vero E6 cells were seeded in a 12 well plate at 3.0 x 10 5 cells/well, ② and cultured in an incubator at 37°C and 5% CO 2 ③ The supernatant was removed and washed twice with 1x PBS. ④ Simultaneously proceed with Shipwreck extract (37℃, 5% CO 2 incubator, 1 hour) and virus adsorption (50 pfu/well, shake/10 min), ⑤ Remove supernatant, add 1.5 mL overlay media , ⑥ The results were confirmed 3 days (72 hours) later.
<실시예 2> 오배자 추출물의 바이러스 감염 억제 실험<Example 2> Virus infection inhibition experiment of Shipwreck extract
현재 SARS-CoV-2의 치료 효과가 있다고 알려진 비교군으로 렘데시비르(Remdesivir, Rem) 5 μM 및 클로로퀴논 포스페이트(chloroquine phosphate, C.P) 10 μM을 사용하여 실험을 진행하였다. 도 1에서 보이는 바와 같이 오배자 추출물과 SARS-CoV-2를 동시에 처리한 후 3일 뒤에 플라크 감소 효과를 측정한 결과, 오배자 추출물은 농도의존적으로 플라크 감소 효과가 우수하며, 특히 고농도에서도 세포독성이 없어 항바이러스 효과를 나타냄을 알 수 있었다. 그러나 비교군으로 사용한 렘데시비르 및 클로로퀴논 포스페이트의 경우에는 플라크의 감소가 나타나지 않아 바이러스의 증식을 억제하지 못함을 확인하였다. 이러한 결과는 오배자 추출물이 숙주세포로 바이러스가 침입하는 것을 억제함을 나타낸다.An experiment was conducted using 5 μM of Remdesivir (Rem) and 10 μM of chloroquine phosphate (CP) as a comparison group that is currently known to be effective in treating SARS-CoV-2. As shown in Figure 1, as a result of measuring the plaque reduction effect 3 days after simultaneously treating the shipwreck extract and SARS-CoV-2, the shipwreck extract had an excellent plaque reduction effect in a concentration-dependent manner, and in particular, it had no cytotoxicity even at high concentrations. It was found to have an antiviral effect. However, in the case of remdesivir and chloroquinone phosphate used as comparison groups, there was no decrease in plaque, confirming that they did not inhibit the proliferation of the virus. These results indicate that shipwreck extract inhibits virus invasion into host cells.
<실시예 3> 오배자 추출물의 SARS-CoV-2 복제억제 실험 실험방법<Example 3> Experimental method for inhibition of SARS-CoV-2 replication by the extract of Shipwort extract
① Vero E6 cells을 12 well plate에 3 x 105 cells/well로 seeding하고, ② 37℃, 5% CO2 인큐베이터에서 배양하였다. ③ 상등액을 제거하고, PBS로 2번 wash 단계를 진행하였다. ④ 바이러스 흡착(virus adsorption) (50 pfu/well, shake/10 min), ⑤ 상등액 제거하고, treatment(오배자 추출물, 37℃, 5% CO2 인큐베이터, 2시간) ⑥ 상등액을 제거하고, add 1.5 mL overlay media, ⑦ 3일(72시간) 뒤에 결과를 확인하였다.① Vero E6 cells were seeded in a 12 well plate at 3 x 10 5 cells/well, and ② were cultured in an incubator at 37°C and 5% CO 2 . ③ The supernatant was removed and washed twice with PBS. ④ Virus adsorption (50 pfu/well, shake/10 min), ⑤ Remove supernatant, treatment (Shipberry extract, 37℃, 5% CO 2 incubator, 2 hours) ⑥ Remove supernatant, add 1.5 mL overlay media, ⑦ The results were confirmed 3 days (72 hours) later.
<실시예 4> 오배자 추출물의 SARS-CoV-2 복제억제 실험 - 1<Example 4> SARS-CoV-2 replication inhibition experiment of Starfish extract - 1
Vero E6 세포에 SARS-CoV-2 감염 후 오배자 추출물을 처리하여 바이러스 복제억제 효능을 측정하였다. 그 결과 도 2와 같이, 오배자 추출물은 농도의존적으로 플라크 감소 효과가 우수하였으며, 고농도인 25 μg/mL에서는 비교군으로 사용된 렘데시비르와 유사하게 100%에 가까운 억제 효과를 보였다.After SARS-CoV-2 infection in Vero E6 cells, the inhibitory effect of virus replication was measured by treating the extract of the gallbladder plant. As a result, as shown in Figure 2, the extract of the gallbladder plant showed an excellent plaque reduction effect in a concentration-dependent manner, and at a high concentration of 25 μg/mL, it showed an inhibitory effect close to 100%, similar to remdesivir used as a comparison group.
<실시예 5> 오배자 추출물의 SARS-CoV-2 복제억제 실험 - 2 <Example 5> SARS-CoV-2 replication inhibition experiment of Starfish extract - 2
오배자 추출물의 항바이러스 효과 검증을 위해 SARS-CoV-2 유전자를 real-time PCR로 정량 분석하였다. 그 결과 도 3과 같이, 오배자 추출물에서 농도의존적으로 viral RNA의 감소가 나타났으며, 고농도인 25 μg/mL 농도에서는 100%에 가까운 항바이러스 효능이 나타났다.To verify the antiviral effect of the shipwreck extract, the SARS-CoV-2 gene was quantitatively analyzed by real-time PCR. As a result, as shown in Figure 3, a concentration-dependent decrease in viral RNA was observed in the extract of Shipwort extract, and at a high concentration of 25 μg/mL, an antiviral efficacy of close to 100% was observed.
<실시예 6> 오배자 성분 PGG의 SARS-CoV-2 복제억제 실험 - 3 <Example 6> SARS-CoV-2 replication inhibition experiment of the shipwreck ingredient PGG - 3
오배자 성분의 항바이러스 효과 검증을 위해, Vero E6 세포에 SARS-CoV-2를 감염시킨 후 오배자 성분을 처리하여 바이러스 복제억제 효능을 측정하였다. 그결과 도 4와 같이 methyl gallate는 각각 16.3%, 18.0%, 21.4%의 바이러스 복제억제효과을 나타냈으며, PGG(penta-O-galloyl-β-D-glucose)의 경우 저농도에서부터 100%의 바이러스 복제억제 효과를 나타냈다.To verify the antiviral effect of the shipwreck components, Vero E6 cells were infected with SARS-CoV-2 and then treated with the shipwreck components to measure the efficacy of inhibiting viral replication. As a result, as shown in Figure 4, methyl gallate showed a virus replication inhibition effect of 16.3%, 18.0%, and 21.4%, respectively, and PGG (penta-O-galloyl-β-D-glucose) inhibited virus replication by 100% from low concentrations. It showed effect.
<실시예 7> 오배자 성분 PGG와 SARS-CoV-2 spike RBD의 molecular docking<Example 7> Molecular docking of shipwreck component PGG and SARS-CoV-2 spike RBD
오배자 추출물이 SARS-CoV-2의 absorption을 방해하는 것으로 나타났기 때문에, viral spike RBD가 숙주세포에 결합하는 것을 오배자 성분에 의해 방해를 받을수 있다. 이에 오배자 성분인 PGG 구조에 SARS-CoV-2 spike receptor-binding domain (RBD)의 molecular docking을 분석하였다. 또한 SARS-CoV-2 spike RBD가 지속적으로 돌연변이를 일으켜 효율적인 백신 및 항바이러스 치료제 개발을 방해하기 때문에 SARS-CoV-2 spike RBD의 변형인 B.1.1.7 spike RBD에 대한 PGG의 결합 친화도를 분석하여, PGG의 잠재적 항바이러스 효과를 평가하였다. Molecular docking 분석에서 계산된 결합 에너지는 하기 표 1과 같다. PGG는 SARS-CoV-2 spike RBD와 B.1.1.7 spike RBD 모두 비슷한 수치를 나타냈다. 이러한 결과는 오배자 추출물이 SARS-CoV-2 spike RBD 및 B.1.1.7 spike RBD 모두에 항바이러스 치료제로서의 잠재력을 가지고 있음을 나타낸다.Since shipwreck extract has been shown to interfere with the absorption of SARS-CoV-2, binding of the viral spike RBD to host cells may be prevented by shipwreck components. Accordingly, we analyzed the molecular docking of the SARS-CoV-2 spike receptor-binding domain (RBD) in the structure of PGG, a component of starfish. In addition, because the SARS-CoV-2 spike RBD continues to mutate, hindering the development of efficient vaccines and antiviral treatments, the binding affinity of PGG for the B.1.1.7 spike RBD, a variant of the SARS-CoV-2 spike RBD, was evaluated. By analyzing, the potential antiviral effect of PGG was evaluated. The binding energies calculated from the molecular docking analysis are shown in Table 1 below. PGG showed similar values for both SARS-CoV-2 spike RBD and B.1.1.7 spike RBD. These results indicate that shipwreck extract has the potential as an antiviral treatment for both SARS-CoV-2 spike RBD and B.1.1.7 spike RBD.
<실시예 8> 오배자 추출물의 체온 상승 억제 효과 확인<Example 8> Confirmation of the effect of inhibiting body temperature increase of the Chinese gall extract
고열 동물 모델에서 상기 준비예 2의 제조방법으로 제조된 오배자 추출물의 해열 효과를 확인하였다. 구체적으로, 실험에 사용된 Sprague-Dawley(SD) rats는 일주일간 사육실 환경에 적응시킨 후 사용하였다 사육실 온도는 25±1℃, 습도는 50~60%로 유지하였다. Light/dark cycle이 12시간 주기로 조절되게 한 후, 고형사료와 물을 제한 없이 공급하였다. 경희대학교 동물실험윤리위원회에서 제공한 지짐서의 원리에 의해서 동물실험을 수행하였다.The antipyretic effect of the shipwreck extract prepared by the preparation method of Preparation Example 2 above was confirmed in a hyperthermic animal model. Specifically, the Sprague-Dawley (SD) rats used in the experiment were used after being adapted to the breeding room environment for a week. The room temperature was maintained at 25 ± 1°C and humidity was maintained at 50-60%. After the light/dark cycle was adjusted to a 12-hour cycle, solid feed and water were supplied without restriction. Animal experiments were performed in accordance with the principles of the guidelines provided by the Animal Experiment Ethics Committee of Kyunghee University.
체온 상승 유발물질(lipopolysaccharides, LPS; sigma, USA) 2.5 mg/kg로 생리식염수에 녹여 상기 실험동물의 복강내로 투여하여 발열을 유발하였다. 실험군은 5마리씩 6군으로 발열 유발 30분 전에 오배자 추출물(25, 50, 100 mg/kg)과 양성대조군(indomethacin, INN, 100 mg/kg)를 경구투여하였다. 발열을 유발하기 전(0 h) 및 유발 6시간 후(6 h)에 직장 내 체온을 측정하여 도 6에 나타내었다.A substance that causes body temperature increase (lipopolysaccharides, LPS; Sigma, USA) was dissolved in physiological saline at 2.5 mg/kg and administered intraperitoneally to the experimental animals to induce fever. The experimental group consisted of 6 groups of 5 animals each, and 30 minutes before fever induction, shipwreck extract (25, 50, 100 mg/kg) and positive control group (indomethacin, INN, 100 mg/kg) were orally administered. Rectal body temperature was measured before (0 h) and 6 hours after (6 h) inducing fever and is shown in Figure 6.
체온 상승 유발물질(LPS) 투여군은 투여 6시간 후 투여 전보다 체온이 상승하였다. 그러나 오배자 추출물를 투여한 군은 모두 농도의존적으로 체온 증가를 억제하는 것을 확인하였다. 이러한 결과로부터 오배자 추출물은 발열을 억제하는 해열 효능이 우수한 것을 확인하였다.In the group administered body temperature raising substance (LPS), body temperature increased 6 hours after administration compared to before administration. However, it was confirmed that all groups administered the gallnut extract suppressed the increase in body temperature in a concentration-dependent manner. From these results, it was confirmed that the Chinese gall extract had excellent antipyretic efficacy in suppressing fever.
상기 실시예들에 의해 본 발명의 오배자 추출물을 사용하여 SARS-CoV-2에 대한 플라크 감소 실험을 진행한 결과 농도의존적으로 유의적인 결과를 확인하였다. 또한, SARS-CoV-2의 viral RNA의 복제억제 실험을 진행한 결과 매우 우수하게 바이러스의 복제를 억제함을 확인하였다. 또한, LPS로 유도된 발열에서도 오배자 추출물이 발열을 억제하는 것을 확인하였다.According to the above examples, as a result of conducting a plaque reduction experiment against SARS-CoV-2 using the shipwreck extract of the present invention, significant results were confirmed in a concentration-dependent manner. In addition, as a result of conducting an experiment to inhibit the replication of viral RNA of SARS-CoV-2, it was confirmed that it inhibited viral replication very well. In addition, it was confirmed that the Starfish extract suppressed fever induced by LPS.
따라서, 오배자 추출물은 SARS-CoV-2의 숙주세포로의 감염 및 숙주세포에서의 바이러스 복제를 모두 억제하여 코로나 바이러스를 억제하는 것으로 나타났다. 이를 통하여 고농도에서 독성이 없으면서 치료 효과가 우수한 코로나 바이러스 감염의 예방 또는 치료용 조성물의 개발이 가능할 것이며, 이를 통하여 코로나 바이러스의 예방, 개선 또는 치료용 조성물로서 추가 연구를 통해 건강기능식품 또는 의약품으로 개발 가능할 것이다.Therefore, it was shown that the extract of the shipwreck inhibits the coronavirus by inhibiting both infection of SARS-CoV-2 into host cells and viral replication in the host cells. Through this, it will be possible to develop a composition for the prevention or treatment of coronavirus infection that is non-toxic at high concentrations and has excellent therapeutic effects. Through this, a composition for the prevention, improvement or treatment of coronavirus will be developed into a health functional food or medicine through additional research. It would be possible.
이상에서 살펴본 바와 같이, 본 발명의 구체적인 실시예를 상세하게 설명되었으나, 본 발명의 사상을 이해하는 당업자는 동일한 사상의 범위 내에서 다른 구성요소를 추가, 변경, 삭제 등을 통하여, 퇴보적인 다른 발명이나 본 발명 사상의 범위 내에 포함되는 다른 실시예를 용이하게 제안할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다. 본 발명의 범위는 상술한 상세한 설명보다는 후술하는 특허청구의 범위에 의하여 나타내어지며, 특허청구의 범위의 의미 및 범위 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.As discussed above, specific embodiments of the present invention have been described in detail, but those skilled in the art who understand the spirit of the present invention may add, change, delete, etc. other components within the scope of the same spirit, thereby creating other regressive inventions. However, other embodiments that are included within the scope of the present invention can be easily proposed. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive. The scope of the present invention is indicated by the scope of the claims described below rather than the detailed description above, and all changes or modified forms derived from the meaning and scope of the claims and their equivalent concepts are included in the scope of the present invention. It should be interpreted as
Claims (11)
상기 조성물은 오배자 추출물을 유효성분으로 포함하고,
상기 오배자 추출물은 에탄올 및 물이 5:5의 부피비로 혼합된 에탄올수용액으로 추출된 것이고,
상기 오배자 추출물은 SARS-CoV-2에 대한 플라크 감소 효과가 있고,
상기 오배자 추출물은 SARS-CoV-2 복제를 억제시키는 것이고,
상기 오배자 추출물은 코로나 바이러스 스파이크 단백질의 세포막 결합을 차단하여 감염을 억제하는 것이고,
상기 SARS-CoV-2의 스파이크 수용체-결합 도메인은 B.1.1.7로 변이된 것인,
SARS-CoV-2 감염의 예방 또는 치료용 약학적 조성물.In a pharmaceutical composition for preventing or treating SARS-CoV-2 infection,
The composition contains Shipwort extract as an active ingredient,
The shipwreck extract was extracted with an ethanol aqueous solution mixed with ethanol and water in a volume ratio of 5:5,
The shipwreck extract has a plaque-reducing effect against SARS-CoV-2,
The shipwreck extract inhibits SARS-CoV-2 replication,
The shipwreck extract inhibits infection by blocking the binding of the coronavirus spike protein to the cell membrane,
The spike receptor-binding domain of the SARS-CoV-2 is mutated to B.1.1.7,
Pharmaceutical composition for preventing or treating SARS-CoV-2 infection.
상기 오배자 추출물은 penta-O-galloyl-β-D-glucose(PGG) 성분을 포함하는 것인, SARS-CoV-2 감염의 예방 또는 치료용 약학적 조성물.According to paragraph 1,
The extract of the shipwreck is a pharmaceutical composition for preventing or treating SARS-CoV-2 infection, which includes a penta-O-galloyl-β-D-glucose (PGG) component.
상기 조성물은 오배자 추출물을 유효성분으로 포함하고,
상기 오배자 추출물은 에탄올 및 물이 5:5의 부피비로 혼합된 에탄올수용액으로 추출된 것이고,
상기 오배자 추출물은 SARS-CoV-2에 대한 플라크 감소 효과가 있고,
상기 오배자 추출물은 SARS-CoV-2 복제를 억제시키는 것이고,
상기 오배자 추출물은 코로나 바이러스 스파이크 단백질의 세포막 결합을 차단하여 감염을 억제하는 것이고,
상기 SARS-CoV-2의 스파이크 수용체-결합 도메인은 B.1.1.7로 변이된 것인,
SARS-CoV-2 감염의 예방 또는 개선용 건강기능식품 조성물.In a health functional food composition for preventing or improving SARS-CoV-2 infection,
The composition contains Shipwort extract as an active ingredient,
The shipwreck extract was extracted with an aqueous ethanol solution in which ethanol and water were mixed in a volume ratio of 5:5,
The shipwreck extract has a plaque-reducing effect against SARS-CoV-2,
The shipwreck extract inhibits SARS-CoV-2 replication,
The shipwreck extract inhibits infection by blocking the binding of the coronavirus spike protein to the cell membrane,
The spike receptor-binding domain of the SARS-CoV-2 is mutated to B.1.1.7,
Health functional food composition for preventing or improving SARS-CoV-2 infection.
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