KR20240094160A - Sanguisorba officinalis Linne extracts inhibiting the infection of the SARS-CoV-2 Delta variant - Google Patents
Sanguisorba officinalis Linne extracts inhibiting the infection of the SARS-CoV-2 Delta variant Download PDFInfo
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/739—Sanguisorba (burnet)
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
Abstract
본 발명은 SARS-CoV-2 델타 변이체에 감염된 개체의 생존을 증가시키는 지유추출물의 용도에 관한 것으로서, 본 조성물은 SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료에 효과가 있다. The present invention relates to the use of oil extract to increase the survival of individuals infected with the SARS-CoV-2 delta variant, and the composition is effective in preventing or treating infection by the SARS-CoV-2 delta variant virus.
Description
본 발명은 SARS-CoV-2 델타 변이체 바이러스로 감염된 개체의 생존을 증가시키는 지유(Sanguisorba officinalis Linne) 추출물의 기능 및 그의 용도에 관한 것이다. The present invention relates to the function and use of Sanguisorba officinalis Linne extract in increasing the survival of individuals infected with SARS-CoV-2 delta variant virus.
지유는 오이풀을 일컬으며, 장미과에 속하는 여러해살이 풀이다. 한국, 중국, 일본, 러시아 등지에 분포해 있으며, 산과 들에서 자라나는 야생초이다. 예로부터 지유는 해독, 화상, 설사, 호흡기 및 위장 질환 완화제로 이용되어 왔으며, 지유의 항알러지, 항암, 항산화 등 다양한 효능이 보고되고 있다. Jiyu refers to cucumber plant and is a perennial plant belonging to the Rosaceae family. It is distributed in Korea, China, Japan, Russia, etc. and is a wild herb that grows in mountains and fields. Since ancient times, fat oil has been used as a detoxifier, burns, diarrhea, respiratory and gastrointestinal disease reliever, and various effects such as anti-allergy, anti-cancer, and antioxidant properties have been reported.
일반적으로 식물을 추출하기 위한 용매로는 메탄올 (methanol), 에탄올 (ethanol) 또는 물을 이용하고 있는데, 지유 열수 추출물은 유용한 효능들이 보고되고 있는데, 구강암 (oralcancer)의 세포 증식을 억제하는 항암효과와 면역능 (immunopotentiation)을 강화시키는 효과가 이전의 연구들을 통해 보고되었다. 열수 추출 방식은 다른 방법들과 비교하여 쉽게 천연물질을 추출할 수 있고, 유용한 성분들을 다량으로 얻을 수 있으며, 에탄올 등과 같은 화학성분을 이용하지 않은 추출방식이므로 독성이 낮아 추출물의 효능이 높고 식품섭취로서 안전성이 있다고 할 수 있다. 또한 지유는 산지에서 자라는 약초과로 재배가 용이하고, 자생력이 높으며 쉽게 구할 수 있다는 장점이 있다.In general, methanol, ethanol, or water are used as solvents for extracting plants, and useful effects of oil hot water extract have been reported, including anticancer effects that inhibit cell proliferation of oral cancer, The effect of enhancing immunopotentiation has been reported in previous studies. Compared to other methods, the hot water extraction method can easily extract natural substances and obtain a large amount of useful ingredients. Since it is an extraction method that does not use chemical components such as ethanol, it has low toxicity, high efficacy of the extract, and good food intake. It can be said to be safe. In addition, Jiyu is a medicinal herb that grows in mountainous areas and has the advantage of being easy to cultivate, highly self-sustaining, and easily available.
한국등록특허 제 10-17842540000 호에는 '지유추출물을 유효성분으로 함유하는 패혈증의 예방 또는 치료용 조성물 및 건강기능식품 조성물'이 개시되어 있고 한국공개특허 제2011-0117540호에는 '지유 추출물을 유효성분으로 함유하는 헬리코박터 감염 질환의 예방 또는 치료용 약학적 조성물 및 건강식품'이 개시되어 있으나, 현재까지 문헌상으로 지유 추출물이 신종 바이러스인 SARS-CoV-2의 변이체인 델타 변이체 바이러스 (Severe acute respiratory syndrome coronavirus 2 Delta variant)의 감염 예방, 개선 또는 치료에 유효함이 보고된 바 없다. Korean Patent No. 10-17842540000 discloses 'A composition for preventing or treating sepsis and a health functional food composition containing oil extract as an active ingredient', and Korean Patent Publication No. 2011-0117540 discloses 'A composition containing oil extract as an active ingredient'. 'Pharmaceutical compositions and health foods for the prevention or treatment of Helicobacter infectious diseases' containing 2 Delta variant) has not been reported to be effective in preventing, improving, or treating infections.
본 발명자들은 지유추출물(QG1)이 SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료 효과가 있음을 확인하여 본 발명을 완성하였다. The present inventors completed the present invention by confirming that oil extract (QG1) is effective in preventing or treating infection by the SARS-CoV-2 delta variant virus.
본 발명이 이루고자 하는 기술적 과제는 지유추출물(QG1)을 유효성분으로 하여 SARS-CoV-2 델타 변이체 바이러스에 의해 유발되는 질환을 치료 및 예방하는 것이다.The technical problem to be achieved by the present invention is to treat and prevent diseases caused by the SARS-CoV-2 delta variant virus using oil extract (QG1) as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명은 지유추출물(QG1)을 유효성분으로 포함하는 SARS-CoV-2 델타 변이체 바이러스(Severe acute respiratory syndrome coronavirus 2 Delta variant)에 의한 감염 예방 또는 치료용 약학적 조성물을 제공한다. In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating infection caused by SARS-CoV-2 Delta variant virus (Severe acute respiratory syndrome coronavirus 2 Delta variant) containing oil extract (QG1) as an active ingredient. to provide.
또한, 본 발명은 지유추출물을 유효성분으로 포함하는 SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving infection by the SARS-CoV-2 delta variant virus containing oil extract as an active ingredient.
또한, 지유를 건조하는 단계;Additionally, the step of drying the oil;
상기 건조된 지유를 30 내지 120℃에서 용매로 추출하는 단계; 및Extracting the dried fat with a solvent at 30 to 120°C; and
상기 추출된 용액을 동결건조하여 분말을 제조하는 단계를 포함하는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염 예방 또는 치료용 약학적 조성물의 제조방법을 제공한다. It provides a method for producing a pharmaceutical composition for preventing or treating infection by SARS-CoV-2 delta variant virus, comprising the step of freeze-drying the extracted solution to prepare a powder.
본 발명의 지유추출물(QG1)을 유효성분으로 포함하는 조성물은 SARS-CoV-2 델타 변이체에 의해 유발된 COVID-19에 대한 치료 효과가 있다. A composition containing oil extract (QG1) of the present invention as an active ingredient has a therapeutic effect on COVID-19 caused by the SARS-CoV-2 delta variant.
도 1은 SARS-CoV-2 델타 변이체 바이러스 감염 햄스터에서 음성대조군(G1), 양성대조군(G2), 지유추출물 투여군(G3~G6)의 체중 감소 결과를 나타낸 것이다.
도 2는 SARS-CoV-2 델타 변이체 바이러스 감염 햄스터의 폐 조직에서 음성대조군(G1), 양성대조군(G2) 및 지유추출물 투여군 (G3~G6)의 바이러스 증식 억제 결과를 qRT-PCR을 통해 나타낸 것이다.
도 3은 SARS-CoV-2 델타 변이체 바이러스 감염 햄스터의 폐 조직에서 음성대조군(G1), 양성대조군(G2) 및 지유추출물 투여군 (G3~G6)의 바이러스 증식 억제 결과를 plaque assay를 통해 나타낸 것이다. p < 0.01; **, p < 0.01
도 4는 SARS-CoV-2 델타 변이체 바이러스 감염 햄스터의 폐 조직에서 음성대조군(G1), 양성대조군(G2), 지유추출물 투여군 (G3~G6)의 바이러스 증식 억제 결과를 조직염색법을 통해 나타낸 것이다.
도 5은 SARS-CoV-2 2 델타 변이체 바이러스 감염 햄스터의 폐 조직에서 음성대조군(G1), 양성대조군(G2) 및 지유추출물 투여군(G3~G6)의 바이러스 증식 억제 결과를 항체조직염색법(H&E 염색법)을 통해 확인한 결과이며, 파란색 원은 염증부위를 나타낸다.
도 6는 SARS-CoV-2 델타 변이체 바이러스에 감염된 햄스터의 폐 조직을 현미경으로 관찰하여 음성대조군(G1), 양성대조군(G2) 및 지유추출물 투여군(G3~G6)의 염증성 결과를 점수(score)로 나타낸 것이다.
도 7는 SARS-CoV-2 델타 변이체 바이러스 감염 햄스터의 폐 조직에서 음성대조군(G1), 양성대조군(G2) 및 지유추출물 투여군(G3~G6)의 염증 억제 결과를 나타낸 것이다. *, p < 0.05; **, p < 0.01 Figure 1 shows the weight loss results of the negative control group (G1), positive control group (G2), and fat extract administration group (G3~G6) in hamsters infected with SARS-CoV-2 delta variant virus.
Figure 2 shows the results of virus proliferation inhibition in the negative control group (G1), positive control group (G2), and fat extract administration group (G3~G6) in the lung tissue of hamsters infected with SARS-CoV-2 delta variant virus through qRT-PCR. .
Figure 3 shows the results of virus proliferation inhibition in the negative control group (G1), positive control group (G2), and fat extract administration group (G3~G6) in the lung tissue of hamsters infected with SARS-CoV-2 delta virus virus through plaque assay. p <0.01; **, p < 0.01
Figure 4 shows the results of virus proliferation inhibition in the negative control group (G1), positive control group (G2), and fat extract administration group (G3~G6) in the lung tissue of hamsters infected with SARS-CoV-2 delta variant virus through tissue staining.
Figure 5 shows the results of virus proliferation inhibition in the negative control group (G1), positive control group (G2), and oil extract administered group (G3 ~ G6) in the lung tissue of hamsters infected with SARS-CoV-2 2 delta virus virus using antibody tissue staining (H&E staining). ), and the blue circle indicates the area of inflammation.
Figure 6 shows the inflammatory results of the negative control group (G1), positive control group (G2), and fat extract administration group (G3 ~ G6) by observing the lung tissue of hamsters infected with SARS-CoV-2 delta variant virus under a microscope. It is expressed as
Figure 7 shows the results of inflammation inhibition in the negative control group (G1), positive control group (G2), and oil extract administration group (G3 to G6) in lung tissue of hamsters infected with SARS-CoV-2 delta variant virus. *, p <0.05; **, p < 0.01
이하, 본 발명을 상세히 설명한다. Hereinafter, the present invention will be described in detail.
본 발명은 지유추출물(QG1)을 유효성분으로 포함하는 SARS-CoV-2 델타 변이체 바이러스에 의한 감염 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating infection caused by SARS-CoV-2 delta variant virus, comprising oil extract (QG1) as an active ingredient.
SARS-CoV-2는 감염에 의해 호흡기 증후 군을 일으키는 바이러스로서, 법정 감염병 제1급으로 지정되어 있다. 현재 세계적 유행병 (pandemic)을 유발하고 있으며 80대 이상의 노령층에서 치사율이 25%에 이를 정도로 매우 심각한 중증을 유발하고 있는 실정이다. 공기중의 비말이나 대인 접촉 등의 경로를 통해 SARS-CoV-2의 비강내 침투가 전파의 주요 원인으로 지목되고 있다. SARS-CoV-2 is a virus that causes respiratory syndrome due to infection and is designated as a class 1 infectious disease by law. It is currently causing a global pandemic and is causing very serious illness in people over 80, with a mortality rate of up to 25%. Invasion of SARS-CoV-2 into the nasal cavity through routes such as airborne droplets or person-to-person contact is considered the main cause of transmission.
사람 체내에 유입된 SARS-CoV-2는 세포 표면에 있는 ACE2 (Angiotensin-Converting Enzyme 2) 수용체와 결합하여 세포내로 침투하고 분열, 증식을 통해 다량의 신규 바이러스를 생성한다(Jackson C.B., et al. Mechanisms of SARS-CoV-2 entry into cells. Nat. Rev. Mol. Cell. Biol. 2021, 5, 1-18.). 생성된 SARS-CoV-2는 세포 밖으로 다시 분비되어 다른 세포에 재침투하는 동일한 과정을 반복하여 증식, 변이를 야기한다. 따라서 SARS-CoV-2의 세포 감염, 세포내 복제 및 증식에 관여하는 기전은 바이러스 치료제 개발의 주요 타깃이다. SARS-CoV-2 that enters the human body binds to the ACE2 (Angiotensin-Converting Enzyme 2) receptor on the cell surface, penetrates into the cell, divides and proliferates, and generates a large amount of new viruses (Jackson C.B., et al. Mechanisms of SARS-CoV-2 entry into cells. Rev. 2021, 5, 1-18. The resulting SARS-CoV-2 is secreted back out of the cell and repeats the same process of re-infiltrating other cells, causing proliferation and mutation. Therefore, the mechanisms involved in cellular infection, intracellular replication, and proliferation of SARS-CoV-2 are major targets for the development of viral therapeutics.
SARS-CoV-2의 유전체 (genome)는 약3만개의 RNA로 구성되어 있으며, SARS-CoV-2의 스파이크 단백질이 세포의 ACE2 수용체 (angiotensin converting enzyme 2)에 결합하여 SARS-CoV-2가 세포에 진입하고 바이러스 복제를 일으킨다.The genome of SARS-CoV-2 is composed of approximately 30,000 RNAs, and the spike protein of SARS-CoV-2 binds to the cell's ACE2 receptor (angiotensin converting enzyme 2), allowing SARS-CoV-2 to enter cells. enters and causes viral replication.
코로나바이러스 표면에는 왕관 모양의 돌기 (스파이크, spike)가 특징적으로 발현된다. 스파이크 단백질은 약 1,200개 아미노산으로 되어 있고, 스파이크1 (S1)과 스파이크2 도메인 (S2 domain)으로 구성되어 있다. 기능적으로 S1은 세포 수용체 결합 그리고 S2는 퓨전 (fusion)에 관여하는 것으로 알려져 있다. Crown-shaped protrusions (spikes) are characteristically expressed on the surface of the coronavirus. Spike protein consists of approximately 1,200 amino acids and consists of Spike 1 (S1) and Spike 2 domains (S2 domain). Functionally, S1 is known to be involved in cell receptor binding and S2 is involved in fusion.
SARS-CoV-2 유전체는 스파이크 단백질 등 구조 단백질뿐만 아니라 바이러스 중합효소, 단백질 분해 효소 등 바이러스 복제 및 감염에 관여하는 단백질을 코딩하는 것으로 알려져 있다.The SARS-CoV-2 genome is known to encode proteins involved in viral replication and infection, such as viral polymerase and proteolytic enzymes, as well as structural proteins such as spike proteins.
SARS-CoV-2는 델타형을 포함 다수의 변이체들을 발생시키고 있으며, 이들 변이 바이러스는 주로 숙주세포에 침투 역할을 하는 스파이크 도메인 (spike domain)내의 유전자 변이 (genetic mutation)에 기인한다(Harvey, W.T., et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol. 2021, 19, 409-424.).SARS-CoV-2 is generating a number of mutants, including the delta type, and these mutant viruses are mainly caused by genetic mutations in the spike domain, which plays a role in infiltrating host cells (Harvey, W.T. , et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat. 2021, 19, 409-424.
본원에서 SARS-CoV-2 바이러스는 그 변이체를 포함하는 것을 의미할 수 있고, 구체적으로 알파, 베타, 감마, 델타, 오미크론, 뮤 등의 변이체 바이러스를 포함할 수 있으나, 이에 제한되는 것은 아니다. As used herein, SARS-CoV-2 virus may mean including its variants, and may specifically include variant viruses such as alpha, beta, gamma, delta, omicron, and mu, but is not limited thereto.
또한 SARS-CoV-2 델타 변이체는 2020년 10월 인도에서 처음 발견된 COVID-19 변이 바이러스로, 당초 '인도 변이'로 불리다가 '델타 변이'로 명칭이 변경되었다. 알파(α, 영국), 베타(β, 남아프리카공화국), 감마(γ, 브라질)와 함께 세계보건기구(WHO)가 지정한 '우려 변이(Variant of Concern)' 중 하나로, 계통 분류체계는 B.1.617이다. WHO는 변이 바이러스가 기존의 발견된 COVID-19 바이러스보다 전파성이 증가하거나 중증도에 변화가 있는 경우, 백신과 치료제 등의 유효성 저하가 확인되는 경우 '우려 변이'로 지정하고 있는데, 델타 변이는 2021년 5월 10일 우려 변이로 분류되었다. In addition, the SARS-CoV-2 delta variant is a COVID-19 mutant virus first discovered in India in October 2020. It was initially called the 'India variant' but was renamed 'Delta variant'. It is one of the ‘Variants of Concern’ designated by the World Health Organization (WHO), along with Alpha (α, UK), Beta (β, South Africa), and Gamma (γ, Brazil), and its phylogenetic classification system is B.1.617. am. WHO designates the mutant virus as a 'variant of concern' if it has increased transmissibility or changes in severity compared to the previously discovered COVID-19 virus, or if it is confirmed that the effectiveness of vaccines and treatments is reduced. The delta mutation will be released in 2021. It was classified as a variant of concern on May 10.
SARS-CoV-2 델타(δ) 변이 (lineage B.1.617.2)는 스파이크 단백질 코딩 서열에 돌연변이가 발생하여 T478K, P681R 및 L452R 치환 변이 등이 확인되었으며, 면역 회피력은 물론 높은 감염력을 가진 것으로 확인되었다. SARS-CoV-2 delta (δ) mutation (lineage B.1.617.2) was confirmed to have mutations in the spike protein coding sequence, including T478K, P681R, and L452R substitution mutations, and was confirmed to have immune evasion ability as well as high infectiousness. It has been done.
본원에서 SARS-CoV-2 델타 변이체(B.1.617.2)는 다양한 하위 변이체(subvariants)를 포함할 수 있으며, 구체적으로 AY.1 내지 AY.28까지의 하위 변이체를 포함할 수 있으나, 이에 제한되는 것은 아니다. Herein, the SARS-CoV-2 delta variant (B.1.617.2) may include various subvariants, and may specifically include subvariants from AY.1 to AY.28, but is limited thereto. It doesn't work.
SARS-CoV-2(Severe acute respiratory syndrome coronavirus 2)는 2019년에 처음 알려진 급성 중증 호흡기 질환 코로나바이러스 2로써 양성 방향의 단일 사슬 RNA 바이러스(positive-sense single-stranded RNA virus)로 분류된다. 이 바이러스에 의해 감염된 질환을 코로나바이러스감염증-19(Coronavirus disease 2019)로 명명하였으며, 줄여서 COVID-19라고 부르고 있다. SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) is an acute severe respiratory disease coronavirus 2 first identified in 2019 and is classified as a positive-sense single-stranded RNA virus. The disease caused by this virus was named coronavirus disease 2019 (Coronavirus disease 2019), and is abbreviated as COVID-19.
상기 SARS-CoV-2에 의한 질환은 코로나바이러스감염증-19 일 수 있다. 상기 코로나바이러스감염증-19는 호흡기 질환일 수 있다. 상기 호흡기 질환은 폐렴일 수 있으며, 코로나바이러스감염증-19의 증상은 발열, 권태감, 기침, 호흡곤란, 가래, 인후통, 두통, 객혈, 오심 및 설사 중 적어도 하나 이상 일 수 있다. The disease caused by SARS-CoV-2 may be coronavirus infection-19. The coronavirus infection-19 may be a respiratory disease. The respiratory disease may be pneumonia, and the symptoms of COVID-19 may be at least one of fever, malaise, cough, difficulty breathing, phlegm, sore throat, headache, hemoptysis, nausea, and diarrhea.
상기 SARS-CoV-2 델타 변이체는 바이러스의 스파이크 단백질(spike protein)에 변이가 발생한 것을 특징으로 할 수 있다. The SARS-CoV-2 delta variant may be characterized by a mutation in the spike protein of the virus.
상기 지유추출물을 유효성분으로 포함하는 조성물은 SARS-CoV-2 델타 변이체 바이러스의 감염을 억제시키는 것을 특징으로 할 수 있으며, SARS-CoV-2 델타 변이체 바이러스에 감염된 개체의 생존을 증가시키는 것을 특징으로 할 수 있다. The composition containing the oil extract as an active ingredient may be characterized by inhibiting infection with the SARS-CoV-2 delta variant virus and increasing the survival of individuals infected with the SARS-CoV-2 delta variant virus. can do.
상기 개체는 질병의 치료를 필요로 하는 대상을 의미하고, 보다 구체적으로는 포유류(예를 들어, 개, 고양이, 말, 토끼, 쥐, 햄스터, 동물원 동물, 소, 돼지, 양과 같은 동물 및 비영장류 포함) 또는 인간을 지칭하며, 특정한 실시형태에서 본원의 상기 개체는 이에 제한되는 것은 아니다. The subject refers to a subject in need of treatment for a disease, and more specifically, mammals (e.g., animals such as dogs, cats, horses, rabbits, rats, hamsters, zoo animals, cattle, pigs, sheep, and non-primates). Including) or a human, and in certain embodiments, the subject herein is not limited thereto.
한편, 상기 조성물은 SARS-CoV-2 델타 변이체 바이러스의 E-gene(외피 단백질; Envelope protein; E-protein) 또는 RdRp(RNA-dependent RNA polymerase)를 저해 또는 억제시키는 것을 특징으로 할 수 있다. Meanwhile, the composition may be characterized as inhibiting or suppressing the E-gene (envelope protein; E-protein) or RdRp (RNA-dependent RNA polymerase) of the SARS-CoV-2 delta variant virus.
상기 RdRp는 SARS-CoV-2 델타 변이체 바이러스를 포함하는 RNA 바이러스에서 RNA의 복제와 전사를 담당하는 단백질이다(Aftab, S.O., et al. Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach. J. Transl. Med. 2020, 18, 275.). The RdRp is a protein responsible for RNA replication and transcription in RNA viruses, including the SARS-CoV-2 delta variant virus (Aftab, S.O., et al. Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach. J. Transl. 2020, 18, 275.
본 발명자들은 SARS-CoV-2 델타 변이체 바이러스의 감염에 대한 치료 및 예방제 개발을 위해 223종의 생약 열수추출물을 이용하여, SARS-CoV-2 델타 변이체 바이러스 감염 개체에 적용한 후, 감염 개체의 생존을 증가시키는 결과를 확인하고 본 발명을 완성하였다.The present inventors used hot water extracts of 223 types of herbal medicine to develop treatments and preventive agents for infection with the SARS-CoV-2 delta variant virus, applied them to individuals infected with the SARS-CoV-2 delta variant virus, and then monitored the survival of the infected individuals. The increasing results were confirmed and the present invention was completed.
본 발명의 구체적인 일 실시예에서, 지유를 이용하여 지유추출물을 제조하였고, 이를 세포 시험 및 햄스터를 이용하여 동물실험에 사용하였다. 그 결과, 지유추출물을 사용하지 않은 음성대조군에 비하여 SARS-CoV-2 델타 변이체 바이러스의 증식 저해 효과를 나타냄으로써 (도 1 내지 도 7 참조), 본 발명의 지유추출물은 SARS-CoV-2의 변이체인 SARS-CoV-2 델타 변이체 바이러스에 의한 감염 예방 또는 치료용 약학적 조성물로 유용하게 이용될 수 있음을 확인하였다. In a specific example of the present invention, a fat extract was prepared using fat oil, and this was used in cell tests and animal tests using hamsters. As a result, it showed an inhibitory effect on the proliferation of the SARS-CoV-2 delta variant virus compared to the negative control group that did not use the oil extract (see Figures 1 to 7), and the oil extract of the present invention was found to be a mutant of SARS-CoV-2. It was confirmed that it can be usefully used as a pharmaceutical composition for preventing or treating infection caused by the SARS-CoV-2 delta variant virus.
또한, 하기 실시예에서 볼 수 있는 바와 같이, 양성대조군으로 RdRp 억제제 (inhibitor)인 몰누피라비르(molnupiravir)는 100 mg/kg내지 300 mg/kg, 바람직하게는 250 mg/kg를 함유하는 MC vehicle을 햄스터에 경구 투여할 수 있으나, 이에 한정되는 것은 아니다. 몰누피라비르의 함량이 상기 범위 미만이면 햄스터에서 SARS-CoV-2의 억제 효과가 미미하고, 상기 범위를 초과하면 비용면에서 실익이 적다. 이때 고농도(250 mg/kg)를 사용한 이유는 몰누피라비르 저농도(15 mg/kg)를 사용하는 족제비인 패럿(ferret)과 다르게 햄스터에서는 고농도 몰누피라비르(molupiravir)가 SARS-CoV-2의 억제 효능을 발휘하기 때문이다(Cox R.M., et al. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nat. Microbiol. 2021, 6(1), 11-18.) (Rosenke K., et al. Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model. Nat. Commun. 2021, 12(1), 2295.). In addition, as can be seen in the following examples, the MC vehicle containing 100 mg/kg to 300 mg/kg, preferably 250 mg/kg, of molnupiravir, an RdRp inhibitor as a positive control group. Can be orally administered to hamsters, but is not limited to this. If the content of molnupiravir is less than the above range, the inhibitory effect of SARS-CoV-2 in hamsters is minimal, and if it exceeds the above range, there is little benefit in terms of cost. The reason why high concentration (250 mg/kg) was used at this time is that unlike ferrets, which use low concentration (15 mg/kg) of molnupiravir, high concentration molupiravir inhibits SARS-CoV-2 in hamsters. This is because it is effective (Cox R.M., et al. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nat. Microbiol. 2021, 6(1), 11-18.) (Rosenke K., et al. Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model. Nat. Commun. 2021, 12(1), 2295.).
상기 지유추출물은 물, 알코올 또는 이들의 혼합물인 용매로 추출되는 것을 특징으로 할 수 있다.The oil extract may be extracted with a solvent that is water, alcohol, or a mixture thereof.
상기 용매는 물, 에탄올, 탄소수 1 내지 5의 저급 알코올 또는 탄소수 1 내지 5의 저급 알코올 수용액일 수 있으나 이에 제한되는 것은 아니다.The solvent may be water, ethanol, a lower alcohol having 1 to 5 carbon atoms, or an aqueous solution of a lower alcohol having 1 to 5 carbon atoms, but is not limited thereto.
상기 용매를 통한 추출 시 추출온도는 20℃ 내지 130℃, 30℃ 내지 120℃ 인 것이 바람직하고, 90℃ 내지 110℃인 것이 더욱 바람직하나, 이에 한정하지 않는다. When extracting using the solvent, the extraction temperature is preferably 20°C to 130°C, 30°C to 120°C, and more preferably 90°C to 110°C, but is not limited thereto.
상기 약학적 조성물은 약제학적으로 허용 가능한 담체, 부형제 또는 희석제를 포함할 수 있다. 발명의 용어 "약학적으로 허용 가능한"이란 상기 조성물에 노출되는 세포나 인간에게 독성이 없는 특성을 나타내는 것을 의미한다. 약학적으로 허용 가능한 담체를 포함하는 조성물은 경구 또는 비경구의 여러 가지 제형일 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 상기 담체, 부형제 및 희석제로는 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 생리식염수, 메틸히드록시벤조에이트, 프로필히드록시 벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유, 덱스트린, 칼슘카보네이트, 프로필렌글리콜 및 리퀴드 파라핀으로 이루어진 군에서 선택된 하나 이상일 수 있으나, 이에 한정되는 것은 아니며, 통상의 담체, 부형제 또는 희석제 모두 사용 가능하다. 상기 성분들은 상기 유효성분인 지유 추출물에 독립적으로 또는 조합하여 추가될 수 있다. The pharmaceutical composition may include a pharmaceutically acceptable carrier, excipient, or diluent. The term "pharmaceutically acceptable" in the present invention means that the composition exhibits non-toxic properties to cells or humans exposed to the composition. The composition containing a pharmaceutically acceptable carrier may be in various oral or parenteral dosage forms. When formulated, it can be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. The carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, It may be one or more selected from the group consisting of polyvinyl pyrrolidone, physiological saline, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate, mineral oil, dextrin, calcium carbonate, propylene glycol, and liquid paraffin. It is not limited, and all common carriers, excipients, or diluents can be used. The ingredients may be added independently or in combination to the active ingredient, oil extract.
상기 약학적 조성물은 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제 및 좌제로 이루어진 군으로부터 선택되는 어느 하나의 제형을 가질 수 있다. The pharmaceutical composition may be any selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, oral solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. It can have one dosage form.
상기 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 60, 카카오지, 라우린지, 글리세롤제라틴 등이 사용될 수 있다.As a base for the suppository, witepsol, macrogol, tween 60, cacao, laurel, glycerol gelatin, etc. can be used.
상기 약학적 조성물은 산제, 과립제, 정제, 캡슐제 및 액체 형태로 이루어진 군으로부터 선택되는 어느 하나의 제형을 가질 수 있다. The pharmaceutical composition may have any one dosage form selected from the group consisting of powder, granule, tablet, capsule, and liquid form.
상기 추출물의 약학적 투여 형태는 단독으로 또는 타 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다.The pharmaceutical dosage form of the extract can be used alone or in combination with other pharmaceutically active compounds, as well as in appropriate combinations.
상기 약학적 조성물은 경구로 투여될 수 있으며, 고형제제 또는 액상제제일 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크같은 윤활제들도 사용된다. 경구투여를 위한 액상제제로는 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, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다.The pharmaceutical composition may be administered orally and may be a solid formulation or a liquid formulation. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include the extract with at least one excipient, such as starch, calcium carbonate, and sucrose. ) or prepared by mixing lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. there is. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.
본 발명의 약학 조성물은 약학적으로 유효한 양으로 투여할 수 있다. 그 투여 용량에 특별한 제약은 없고, 체내 흡수도, 체중, 환자의 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도 등에 따라 변화될 수 있다. 본 발명의 약학적 조성물은 유효량 범위를 고려하여 제조하도록 하며, 이렇게 제형화된 단위 투여형 제제는 필요에 따라 약제의 투여를 감시하거나 관찰하는 전문가의 판단과 개인의 요구에 따라 전문화된 투약법을 사용하거나 일정 시간 간격으로 수회 투여할 수 있다. 상기 투여는 바람직하게는 하루에 한 번 투여할 수도 있고, 수 회 나누어 투여할 수도 있다.The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount. There are no particular restrictions on the administered dose, and it may vary depending on body absorption, body weight, patient's age, gender, health condition, diet, administration time, administration method, excretion rate, and severity of disease. The pharmaceutical composition of the present invention is manufactured taking into account the effective dose range, and the unit dosage form formulated in this way can be prepared according to the judgment of an expert who monitors or observes the administration of the drug as needed and a specialized dosing method according to the individual's needs. It can be used or administered several times at regular time intervals. The above administration may preferably be administered once a day, or may be administered several times.
상기 지유추출물은 오이풀 (Sanguisorba officinalis L.)의 뿌리 및 긴오이풀 (Sanguisorba longifolia) 뿌리로 또는 이들의 혼합물로 이루어진 그룹에서 선택된 어느 하나 이상에서 추출되는 것을 특징으로 할 수 있다. The oil extract may be extracted from one or more of the roots of Sanguisorba officinalis L., the roots of Sanguisorba longifolia, or mixtures thereof.
또한, 본 발명은 지유추출물을 유효성분으로 포함하는 SARS-CoV-2 델타 변이체 바이러스에 의한 감염 또는 이로 인한 질환의 예방 또는 개선용 식품 조성물을 제공한다. In addition, the present invention provides a food composition for preventing or improving infection by or disease caused by SARS-CoV-2 delta variant virus, comprising oil extract as an active ingredient.
상기 식품은 건강기능식품 또는 음료 중 어느 하나 이상인 것을 특징으로 할 수 있다.The food may be characterized as being one or more of health functional foods or beverages.
상기 지유추출물을 식품첨가물로 사용하는 경우, 상기 지유추출물을 그대로 첨가하거나 다른 식품 또는 식품성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 그의 사용목적 (예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 추출물은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가될 수 있다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.When using the fat extract as a food additive, the fat extract can be added as is or used together with other foods or food ingredients, and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). Generally, when producing food or beverages, the extract of the present invention may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw materials. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be 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 건강기능식품의 종류에는 특별한 제한은 없다. 상기 지유추출물을 첨가할 수 있는 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함할 수 있다. There are no particular restrictions on the types of health functional foods. Examples of foods to which the oil extract can be added include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, and drink preparations. , alcoholic beverages and vitamin complexes, etc., and can include all health functional foods in the conventional sense.
본 발명의 건강기능음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다.The health functional beverage composition of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients, like conventional beverages. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, natural sweeteners such as thaumatin and stevia extract or synthetic sweeteners such as saccharin and aspartame can be used.
상기 건강기능식품 외에 본 발명의 건강기능식품은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0.01 내지 2 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above health functional food, the health functional food of the present invention includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, and preservatives. , glycerin, alcohol, and carbonating agents used in carbonated beverages. In addition, it may contain pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These ingredients can be used independently or in combination. The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 2 parts by weight per 100 parts by weight of the composition of the present invention.
상기 지유추출물은 하기의 단계를 포함하는 제조방법으로 제조되는 것이 바람직하나 이에 한정되지 않는다:The oil extract is preferably prepared by a manufacturing method including the following steps, but is not limited thereto:
1) 지유를 건조하는 단계;1) Drying the oil;
2) 상기 건조된 지유를 30 내지 120℃에서 용매로 추출하는 단계; 및2) extracting the dried fat with a solvent at 30 to 120°C; and
3) 상기 추출된 용액을 동결건조하여 분말을 제조하는 단계3) Freeze-drying the extracted solution to produce powder.
본 발명은 1) 지유를 건조하는 단계;The present invention includes the steps of 1) drying fat oil;
2) 상기 건조된 지유를 30 내지 120℃에서 용매로 추출하는 단계; 및2) extracting the dried fat with a solvent at 30 to 120°C; and
3) 상기 추출된 용액을 동결건조하여 분말을 제조하는 단계를 포함하는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물 제조방법을 제공한다.3) It provides a method for manufacturing a pharmaceutical composition for preventing or treating infection by SARS-CoV-2 delta variant virus, comprising the step of freeze-drying the extracted solution to prepare a powder.
또한, 본 발명은 1) 지유를 건조하는 단계;In addition, the present invention includes the steps of 1) drying fat oil;
2) 상기 건조된 지유를 30 내지 120℃에서 용매로 추출하는 단계; 및2) extracting the dried fat with a solvent at 30 to 120°C; and
3) 상기 추출된 용액을 동결건조하여 분말을 제조하는 단계를 포함하는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 개선용 건강기능식품 조성물 제조방법을 제공한다.3) It provides a method for manufacturing a health functional food composition for preventing or improving infection by SARS-CoV-2 delta variant virus, comprising the step of freeze-drying the extracted solution to produce a powder.
상기 방법에 있어서, 단계 1)의 지유는 오이풀 또는 긴오이풀을 재배한 것 또는 시판되는 것 등 제한 없이 사용할 수 있으며, 잎, 뿌리, 줄기 및 가지 등 어느 것도 이용가능하고, 이에 한정하지 않으나 오이풀의 뿌리 또는 긴오이풀 뿌리를 이용하는 것이 가장 바람직하다.In the above method, the oil of step 1) can be used without limitation, such as cultivated or commercially available cucumber grass or long cucumber grass, and any leaves, roots, stems, and branches can be used, but is not limited to these, but is not limited to cucumber grass. It is most desirable to use the root or the root of the long cucumber plant.
상기 방법에 있어서, 단계 1)의 추출 용매는 물, 알코올, 주정 또는 이들의 혼합물 및 유기 용매를 사용하는 것이 바람직하다. 상기 알코올로는 탄소수1 내지 탄소수5의 저급 알코올을 이용하는 것이 바람직하며, 저급 알코올로는 에탄올 또는 메탄올을 이용하는 것이 바람직하다. 추출방법으로는 열수추출, 진탕추출, Soxhlet 추출 또는 환류 추출을 이용하는 것이 바람직하나 이에 한정되지 않는다. 상기 추출 용매를 건조된 지유의 총 중량에 5 내지 30배 첨가하여 추출하는 것이 바람직하고, 20배 첨가하여 추출하는 것이 더욱 바람직하다. 추출 온도는 20℃ 내지 130℃ 인 것이 바람직하고, 90℃ 내지 110℃인 것이 더욱 바람직하나, 이에 한정하지 않는다. 또한, 추출 시간은 2 내지 48시간인 것이 바람직하며, 15 내지 30시간인 것이 더욱 바람직하고, 24시간인 것이 가장 바람직하나, 이에 한정하지 않는다. 아울러, 추출 횟수는 1 내지 5회인 것이 바람직하며, 3 내지 4회 반복 추출하는 것이 더욱 바람직하고, 3회인 것이 가장 바람직하나, 이에 한정되는 것은 아니다. In the above method, the extraction solvent in step 1) is preferably water, alcohol, alcohol, or a mixture thereof and an organic solvent. It is preferable to use a lower alcohol having 1 to 5 carbon atoms as the alcohol, and it is preferable to use ethanol or methanol as the lower alcohol. The extraction method is preferably hot water extraction, shaking extraction, Soxhlet extraction, or reflux extraction, but is not limited to these. It is preferable to extract by adding 5 to 30 times the total weight of the dried oil, and more preferably by adding 20 times the extraction solvent to the total weight of the dried fat. The extraction temperature is preferably 20°C to 130°C, and more preferably 90°C to 110°C, but is not limited thereto. In addition, the extraction time is preferably 2 to 48 hours, more preferably 15 to 30 hours, and most preferably 24 hours, but is not limited thereto. In addition, the number of extractions is preferably 1 to 5 times, more preferably 3 to 4 times, and most preferably 3 times, but is not limited thereto.
상기 지유추출물은 30 내지 95% 주정 추출물인 것이 바람직하고, 40 내지 90% 주정 추출물인 것이 보다 바람직하며, 50 내지 80% 주정 추출물인 것이 가장 바람직하고, 상기 30%미만 주정 추출물의 경우에는 추출 효율이 낮아져 목적으로 하는 SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료효과를 나타내지 못할 수 있고, 95%초과 주정 추출물의 경우, 지유 추출물의 생산 단가를 높이게 되어 좋지 않다.The oil extract is preferably 30 to 95% alcohol extract, more preferably 40 to 90% alcohol extract, and most preferably 50 to 80% alcohol extract. In the case of less than 30% alcohol extract, the extraction efficiency This is lowered and may not show the intended prevention or treatment effect of infection by the SARS-CoV-2 delta variant virus, and in the case of alcohol extract exceeding 95%, it is not good because it increases the production cost of the oil extract.
상기 제조방법을 통해 제조된 지유 추출물을 유효성분으로 포함하는 조성물은 SARS-CoV-2 변이체 바이러스에 의한 감염의 예방 또는 치료에 효과를 나타내는 것을 특징으로 할 수 있다. A composition containing the oil extract prepared through the above manufacturing method as an active ingredient may be characterized as being effective in preventing or treating infection by the SARS-CoV-2 variant virus.
이하, 본 발명을 실시예 및 실험예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail through examples and experimental examples.
다만, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예 및 실험예에 의하여 한정되는 것은 아니다. However, the following examples and experimental examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following examples and experimental examples.
실시예 1. 지유 추출물의 제조 방법 Example 1. Method for producing oil extract
건조된 지유(오이풀 (Sanguisorba officinalis Linne)의 뿌리)에 건조 지유 총 중량의 20배 무게의 증류수를 첨가하여 1시간 30분동안 냉침하였다. 그 후 대형 전탕기를 이용하여 100℃에서 1시간 30분동안 리플럭스(reflux)하여 용액을 추출했다. 추출된 용액을 감압여과하여 불순물을 제거한 뒤, -20℃에서 동결 건조하여 분말을 제조하였다. 상기 동결 건조된 0.2 g 지유 분말을 10 mL 증류수에 넣어 지유 추출물 함유 용액 (20 mg/ml)을 제조하여 인비트로 (in-vitro) 및 동물 시험에 사용하였다. Distilled water 20 times the weight of the total weight of dried oil was added to dried oil (root of Sanguisorba officinalis Linne) and cold soaked for 1 hour and 30 minutes. Afterwards, the solution was extracted by refluxing at 100°C for 1 hour and 30 minutes using a large water boiler. The extracted solution was filtered under reduced pressure to remove impurities, and then freeze-dried at -20°C to prepare a powder. 0.2 g of the freeze-dried oil powder was added to 10 mL of distilled water to prepare a solution containing oil extract (20 mg/ml), which was used in in-vitro and animal tests.
실시예 2. 햄스터 동물실험을 통한 SARS-CoV-2 델타 변이체 바이러스 감염 동물 모델 구축 및 시험 물질 경구 투여Example 2. Construction of an animal model for SARS-CoV-2 delta variant virus infection through hamster animal experiments and oral administration of test substances
지유추출물의 농도에 따른, 햄스터 동물시험에서 SARS-CoV-2 델타 변이체 바이러스의 분열 증식 및 생존력 억제에 의한 감염 햄스터의 생존 여부를 확인하기 위해서, 공지된 바이러스인 SARS-CoV-2 델타 변이 바이러스(NCCP43390)를 2x105 PFU/mL 사용하여 SARS-CoV-2 델타 변이체 바이러스 감염 햄스터 동물 모델을 구축하였다. 양성대조군으로 RdRp 억제제(inhibitor)인 몰누피라비르(molnupiravir)를 함유하는 대조군 약물과 지유추출물 및 약물이 전혀 포함되지 않은 부형제인 메틸셀루로즈 (methylcellulose, MC) vehicle를 각각 경구 투여하였다. 각각의 시험 물질은 매일 2회로 나누어 투여 되었다. In order to determine the survival of infected hamsters by inhibiting the division, proliferation and viability of the SARS-CoV-2 delta variant virus in hamster animal tests depending on the concentration of the oil extract, the known virus, SARS-CoV-2 delta variant virus ( A hamster animal model of SARS-CoV-2 delta variant virus infection was constructed using 2x10 5 PFU/mL (NCCP43390). As a positive control group, a control drug containing molnupiravir, an RdRp inhibitor, and methylcellulose (MC) vehicle, an excipient containing no oil extract and no drug, were administered orally, respectively. Each test substance was administered twice daily.
또한, 실시예 2에서는 지유추출물의 투여량에 따른 바이러스의 증식 억제 효능을 알아보기 위하여, 표 1와 같이 분류군을 설정하였다. In addition, in Example 2, in order to determine the effectiveness of inhibiting virus growth according to the dosage of oil extract, taxa were set as shown in Table 1.
G1: 부형제대조군, G2: 양성대조군, G3-G6: 시험물질(지유추출물) 투여군. G1: Excipient control group, G2: Positive control group, G3-G6: Test substance (fat extract) administration group.
표 1에서와 같이, 바이러스 감염 직후 음성대조군(G1)으로는 부형제인 메틸셀루로즈(methylcellulose, MC) vehicle을 경구투여 하였고, 양성대조군(G2)으로는 RdRp 억제제 (inhibitor)인 몰누피라비르(molnupiravir) (머크 사, 미국)의 고농도 (250 mg/kg)를 함유하는 MC vehicle을 경구투여 하였다. 지유추출물 투여군 (G3~G6)으로는 각각 지유추출물을 25 mg/kg, 50mg/kg, 75 mg/kg 및 100 mg/kg 을 경구투여 하여 실험군을 설정하였다. 또한, Student’s t-test를 이용하여 시험물질 투여군간 유의성을 검정하였고, 통계학적 분석은 Prism 7.04 (GraphPad Software Inc., San Diego, CA, USA)를 이용하였으며, p값이 0.05 미만일 경우, 통계학적으로 유의한 것으로 판정하였다. As shown in Table 1, immediately after virus infection, methylcellulose (MC) vehicle, an excipient, was orally administered to the negative control group (G1), and molnupiravir, an RdRp inhibitor, was administered to the positive control group (G2). ) (Merck, USA) MC vehicle containing a high concentration (250 mg/kg) was orally administered. The oil extract administration group (G3~G6) was set up by oral administration of 25 mg/kg, 50 mg/kg, 75 mg/kg, and 100 mg/kg of oil extract, respectively. In addition, Student's t-test was used to test the significance between test substance administration groups, and statistical analysis was performed using Prism 7.04 (GraphPad Software Inc., San Diego, CA, USA). If the p value is less than 0.05, statistical analysis was performed. It was judged to be significant.
실시예 3. SARS-CoV-2 델타 변이체 바이러스 감염 햄스터에 대한 지유 추출물의 몸무게 감소 억제 효과 Example 3. Inhibitory effect on body weight loss of Jiyu extract on hamsters infected with SARS-CoV-2 delta variant virus
실시예 2에서와 같이 SARS-CoV-2 델타 변이체 바이러스 접종 후 감염 햄스터에 시험물질 투여하고 그 당일부터 4 일 동안 매일 전자저울을 이용하여 개체 별 체중을 측정하였다.As in Example 2, after inoculation with the SARS-CoV-2 delta variant virus, the test substance was administered to the infected hamster, and the body weight of each individual was measured using an electronic scale every day for 4 days from that day.
그 결과 도 1에 나타난 것과 같이, SARS-CoV-2 델타 변이체 바이러스 감염 햄스터에 음성 대조군인 vehicle만 투여하였을 시 감염 1 내지 4일 사이에 몸무게가 현저히 감소하였다. 그에 반해, 지유추출물 투여군은 양성대조군인 몰누피라비르 (molupiravir) 투여군과 유사하게 감염된 햄스터의 몸무게 감소를 억제하는 효과를 나타냈다. 이러한 결과는 지유추출물이 감염 햄스터의 동물 시험에서 SARS-CoV-2 델타 변이체 바이러스의 분열 증식 및 생존력을 강하게 억제하여 생체 내 항상성을 회복시킴으로써 몸무게의 정상화를 유도했음을 나타낸다. As a result, as shown in Figure 1, when only the negative control vehicle was administered to hamsters infected with the SARS-CoV-2 delta variant virus, body weight was significantly reduced between 1 and 4 days of infection. On the other hand, the group administered fat extract showed an effect of suppressing the weight loss of infected hamsters, similar to the group administered molupiravir, a positive control group. These results indicate that the oil extract strongly inhibited the proliferation and viability of the SARS-CoV-2 delta variant virus in animal tests on infected hamsters, restoring homeostasis in vivo and leading to normalization of body weight.
또한, 실험 기간 중 사망을 포함한 실험 물질의 투여에 의한 이상 증상은 관찰되지 않았으며, SARS-CoV-2 델타 변이체 바이러스 감염 햄스터에 지유추출물의 투여하였을 때, 몸무게 정상화를 나타냄으로써 생체 내 적합성을 확인할 수 있었다. In addition, no abnormal symptoms, including death, were observed due to administration of the test substance during the experiment period, and when the oil extract was administered to hamsters infected with the SARS-CoV-2 delta variant virus, body weight was normalized, confirming in vivo compatibility. I was able to.
실시예 4. Real time RT-PCR 분석법을 이용하여 지유 추출물에 의한 감염 햄스터 폐에서 SARS-CoV-2 델타 변이체 바이러스 증식 억제 확인 Example 4. Confirmation of inhibition of SARS-CoV-2 delta variant virus proliferation in infected hamster lungs by oil extract using real time RT-PCR analysis
감염 4일째 (4 Day post infection, 4 DPI) 햄스터의 폐조직에서 병변 부위 일부를 채취하여 Wizol™ (WizbioSolution, Seongnam, Korea) 시약 일정량을 넣고 조직 분쇄용 비드를 이용하여 분쇄한 후 상층액에서 전체(total) RNA를 추출하였다. 추출된 전체 RNA는 Nanodrop(NanoDrop2000, Thermo scientific)을 이용하여 정량하였고 감염 햄스터 폐 조직 유래 바이러스 잔존량을 총 RNA ng 또는 μg 당 바이러스 유전자의 copy 수로 정량 분석하였다. 감염 4일째 모든 군에서 폐조직을 분석하여 결과를 관찰하였으며, SARS-CoV2 델타 변이체 바이러스에 특이적인 유전자 E-gene 프라이머 (primer), RdRp 프라이머를 사용하여 Real-time RT-PCR을 수행하였다. Real-time RT-PCR에 사용된 프라이머 염기서열은 표 2에 기재되어 있다. On the 4th day post infection (4 DPI), a portion of the lesion area was collected from the hamster's lung tissue, a certain amount of Wizol™ (WizbioSolution, Seongnam, Korea) reagent was added, and the entire tissue was pulverized using tissue grinding beads. (total) RNA was extracted. The extracted total RNA was quantified using Nanodrop (NanoDrop2000, Thermo scientific), and the residual amount of virus derived from infected hamster lung tissue was quantitatively analyzed as the number of copies of the viral gene per ng or μg of total RNA. On the 4th day of infection, lung tissue was analyzed in all groups and the results were observed, and real-time RT-PCR was performed using E-gene primers and RdRp primers specific to the SARS-CoV2 delta variant virus. Primer sequences used for real-time RT-PCR are listed in Table 2.
그 결과 도 2에 나타난 것과 같이, 폐 조직 내 바이러스의 잔존량은 음성대조군(G1) 대비 지유추출물 50 mg/kg 투여군(G4군), 지유추출물 75 mg/kg 투여군(G5군), 및 지유추출물 100 mg/kg 투여군(G6군)에서 현저히 낮게 측정되었고, 이러한 결과는 지유추출물이 SARS-CoV2 델타 변이체 바이러스의 분열 증식을 차단하여 바이러스의 생존을 억제하고 있음을 나타내고 있다. As a result, as shown in Figure 2, the remaining amount of virus in lung tissue was compared to the negative control group (G1), the group administered 50 mg/kg of fat extract (G4 group), the group administered 75 mg/kg of fat extract (G5 group), and the group administered 75 mg/kg of fat extract (G5 group). It was measured significantly lower in the 100 mg/kg administration group (G6 group), and these results indicate that the oil extract blocks the division and proliferation of the SARS-CoV2 delta variant virus and inhibits the survival of the virus.
따라서, 지유추출물은 햄스터 폐에서의 SARS-CoV2 델타 변이체 바이러스 증식을 효과적으로 억제한다는 것을 알 수 있었다.Therefore, it was found that oil extract effectively inhibits the proliferation of SARS-CoV2 delta variant virus in hamster lungs.
실시예 5. Plaque assay를 이용하여 지유 추출물에 의한 햄스터 폐에서 SARS-CoV-2 델타 변이체 바이러스 증식 억제 확인Example 5. Confirmation of inhibition of SARS-CoV-2 delta variant virus proliferation in hamster lungs by oil extract using plaque assay
각 실험군에서 햄스터의 폐조직에서 채취한 폐 조직을 이용하여, 아래와 같이 조직 g당 plaque 수를 산출하였다. Using lung tissue collected from hamster lung tissue in each experimental group, the number of plaques per g of tissue was calculated as follows.
감염 4일째(4 DPI) 햄스터의 폐조직에서 채취한 폐 조직을 1 mg 당 10 μl의 PBS를 첨가하여 균질화(homogenization)하였다. 5,000 rpm에서 3 분간 원심분리 후 상층액을 회수하고 PBS로 연속 희석 (serial dilution)에 의해 부피를 200 μl로 맞춘 후 12-well plate에서 자라는 Vero E6 세포에 처리하였다. 1 시간 동안 15 분 간격으로 바이러스가 골고루 Vero E6 세포에 접촉하도록 흔들어 준 뒤, 상층액을 제거하고 1 % agarose가 포함된 agarose overlay 배지(medium)을 1 ml씩 각 well에 첨가하였다. Agarose overlay 배지가 굳은 것을 확인한 후 12-well plate를 뒤집어 96 시간 동안 배양하여 plaque의 형성 여부를 관찰하였다. Agarose overlay 배지를 제거하고 크리스탈 바이올렛 (crystal violet)으로 염색하였다. 시료의 희석 배수와 알려진 copy 수의 바이러스로부터 유래한 plaque 수를 비교하여 조직 g당 plaque 수를 산출하였다. Lung tissue collected from hamsters on the 4th day of infection (4 DPI) was homogenized by adding 10 μl of PBS per 1 mg. After centrifugation at 5,000 rpm for 3 minutes, the supernatant was recovered, adjusted to a volume of 200 μl by serial dilution with PBS, and then treated with Vero E6 cells growing in a 12-well plate. After shaking the virus every 15 minutes for 1 hour to evenly contact the Vero E6 cells, the supernatant was removed, and 1 ml of agarose overlay medium (medium) containing 1% agarose was added to each well. After confirming that the agarose overlay medium had hardened, the 12-well plate was turned over and cultured for 96 hours to observe the formation of plaques. Agarose overlay medium was removed and stained with crystal violet. The number of plaques per g of tissue was calculated by comparing the dilution factor of the sample and the number of plaques derived from viruses of known copy number.
그 결과 도 3에 나타난 것과 같이, 조직 g 당 plaque 수는 음성대조군(G1) 대비 지유추출물 50 mg/kg 투여군(G4군), 지유추출물 75 mg/kg 투여군(G5군), 및 지유추출물 100 mg/kg 투여군(G6군)에서 현저히 낮다는 것이 확인되었다. 그러므로, 음성대조군(G1) 대비 지유추출물의 투여량이 농도-의존적으로 증가할수록 햄스터 폐에서의 SARS-CoV2 델타 변이체 바이러스 증식을 억제한다는 것을 알 수 있었다. As a result, as shown in Figure 3, the number of plaques per g of tissue was compared to the negative control group (G1) in the group administered 50 mg/kg of fat extract (G4 group), the group administered 75 mg/kg fat extract (G5 group), and the group administered 100 mg of fat extract. It was confirmed that it was significantly lower in the /kg administration group (G6 group). Therefore, compared to the negative control group (G1), it was found that as the dose of oil extract increased in a concentration-dependent manner, the proliferation of SARS-CoV2 delta virus in hamster lungs was inhibited.
실시예 6. 항체조직염색법 (immunohistochemistry)을 이용하여 지유 추출물에 의한 햄스터 폐에서 SARS-CoV-2 델타 변이체 바이러스 증식 억제 확인 Example 6. Confirmation of inhibition of SARS-CoV-2 delta variant virus proliferation in hamster lungs by oil extract using antibody tissue staining (immunohistochemistry)
감염 4일째 (4 DPI) 각 군당 3마리의 햄스터 폐조직을 채취하여 파라핀 블록을 제조하였고 5 μm 두께로 조직을 절편하였다. 그 후 SARS-CoV-2 델타 변이체 바이러스 특이적인 뉴클레오캡시드 (nucleocapsid)에 대한 항체(Cat# 40143-MM05; Sino Biological Inc.)를 이용하여 공지의 조직염색법을 사용하여 수행하였다. On the 4th day of infection (4 DPI), lung tissues from 3 hamsters in each group were collected, paraffin blocks were prepared, and the tissues were sectioned at 5 μm thickness. Afterwards, a known tissue staining method was performed using an antibody against the SARS-CoV-2 delta variant virus-specific nucleocapsid (Cat# 40143-MM05; Sino Biological Inc.).
그 결과 도 4에 나타난 것과 같이, 음성 대조군(G1)의 경우 햄스터의 폐조직내 상피세포에서 SARS-CoV-2 델타 변이체 바이러스의 감염을 나타내는 강한 갈색 반응(뉴클레오캡시드 반응)이 관찰되었다. 그에 반해, 지유추출물 투여군(G3~G6)의 경우 뉴클레오캡시드 반응이 양성 대조군(G2)인 몰누피라비르와 동등한 정도의 효과가 있음을 확인할 수 있었다. As a result, as shown in Figure 4, in the case of the negative control group (G1), a strong brown reaction (nucleocapsid reaction) indicating infection with the SARS-CoV-2 delta variant virus was observed in epithelial cells within the lung tissue of hamsters. On the other hand, in the case of the oil extract administration group (G3 to G6), it was confirmed that the nucleocapsid reaction was as effective as molnupiravir, the positive control group (G2).
구체적으로, 도 4에 나타난 결과를 통해 햄스터 폐조직에서 SARS-CoV-2 델타 변이체 바이러스 증식이 음성대조군(G1) 대비 지유추출물 50 mg/kg 투여군(G4군), 지유추출물 75 mg/kg 투여군(G5군) 및 지유추출물 100 mg/kg 투여군(G6군)에서 현저히 낮다는 것이 확인되었다. 따라서, 조직학적 평가를 통해 지유추출물이 50 mg/kg 이상 투여될 시, SARS-CoV-2 델타 변이체 감염에 의해 유발된 염증을 완화시키며 바이러스 증식을 억제한다는 것을 확인할 수 있었다. 결론적으로 지유추출물은 SARS-CoV-2 델타 변이체 바이러스의 증식을 억제하는 효과가 양성 대조군(G2)인 몰누피라비르와 동등 이상으로 있다는 것을 알 수 있었다. Specifically, the results shown in Figure 4 show that SARS-CoV-2 delta variant virus proliferation in hamster lung tissue was significantly higher in the group administered 50 mg/kg of fat extract (G4 group) and the group administered 75 mg/kg of fat extract compared to the negative control group (G1) ( It was confirmed that it was significantly lower in the group G5) and the group administered 100 mg/kg of oil extract (group G6). Therefore, through histological evaluation, it was confirmed that when 50 mg/kg or more of the oil extract was administered, it alleviated inflammation caused by SARS-CoV-2 delta variant infection and inhibited viral proliferation. In conclusion, it was found that the oil extract had an effect of inhibiting the proliferation of the SARS-CoV-2 delta variant virus that was equal to or greater than that of molnupiravir, the positive control group (G2).
실시예 7. 지유 추출물의 SARS-CoV-2 델타 변이체 바이러스에 의한 햄스터 염증 유발 억제 효능 Example 7. Efficacy of Jiyu extract to suppress inflammation in hamsters caused by SARS-CoV-2 delta variant virus
감염 4일째(4 DPI) 햄스터를 각 군당 3 마리 부검하여 조직을 10% NBF(Neutral Buffered Formalin) 용액에 고정한 후 조직병리검사를 수행하였다. 10% NBF에 고정된 조직을 이용하여 파라핀 블록을 제조한 후 5 μm 두께로 조직을 절편 하였다. 그 후 H&E(Hematoxylin & Eosin) 염색과 광학 현미경 관찰을 통해, 폐 조직내의 염증 스코어링이 평가되었다. On the 4th day of infection (4 DPI), 3 hamsters per group were autopsied, the tissues were fixed in 10% NBF (Neutral Buffered Formalin) solution, and histopathological examination was performed. A paraffin block was prepared using tissue fixed in 10% NBF, and the tissue was sectioned at a thickness of 5 μm. Inflammation scoring within lung tissue was then evaluated through H&E (Hematoxylin & Eosin) staining and light microscopy.
도 5에서 나타난 것과 같이, H&E 염색 결과 음성 대조군(G1)의 경우 양성대조군(G2) 및 지유추출물(G3~G6) 대비 햄스터의 폐조직 내에서 SARS-CoV-2 델타 변이체 바이러스에 의한 염증반응이 관찰되었다. As shown in Figure 5, as a result of H&E staining, the negative control group (G1) showed an inflammatory reaction caused by the SARS-CoV-2 delta variant virus in the lung tissue of hamsters compared to the positive control group (G2) and fat extract (G3 ~ G6). was observed.
도 6에 나타난 결과는 염증 정도에 따라 0 - 3점 단위로 점수화한 염증 스코어링 결과이다. 0 값은 병변이 없는 수치이고 10% 이하는 1점, 10 % - 50 %는 2점, 50 % 이상은 3 점을 부여하였으며 출혈이나 부종이 관찰될 시 0.5 점을 추가로 부여하였다. 그 결과 도 6 또는 도 7에 나타난 것처럼, 염증 스코어링 평가 결과, 염증 총 누적 점수(cumulative score)는 음성대조군(G1)에 비해 지유추출물 50 mg/kg 투여군(G4), 지유추출물 75 mg/kg 투여군(G5) 및 지유추출물 100 mg/kg 투여군(G6)이 현저히 낮다는 것을 확인되었다. The results shown in Figure 6 are inflammation scoring results scored on a scale of 0 to 3 points depending on the degree of inflammation. A value of 0 indicates no lesion, less than 10% was given 1 point, 10% - 50% was given 2 points, more than 50% was given 3 points, and if bleeding or edema was observed, an additional 0.5 point was given. As a result, as shown in Figure 6 or Figure 7, as a result of the inflammation scoring evaluation, the total cumulative inflammation score was compared to the negative control group (G1) in the group administered 50 mg/kg of fat extract (G4) and the group administered 75 mg/kg of fat extract. (G5) and the group administered 100 mg/kg of oil extract (G6) were confirmed to have significantly lower levels.
그러므로, 조직학적 평가 결과, 지유추출물이 50 mg/kg 이상 투여될 시, SARS-CoV-2 델타 변이체 감염에 의해 유발된 염증을 완화시키며 바이러스 증식을 억제한다는 것을 확인할 수 있었다. Therefore, as a result of histological evaluation, it was confirmed that when 50 mg/kg or more of the oil extract was administered, it alleviated inflammation caused by SARS-CoV-2 delta variant infection and inhibited viral proliferation.
서열목록 전자파일 첨부Sequence list electronic file attached
Claims (16)
상기 SARS-CoV-2 델타 변이체 바이러스는 그 하위변이체(subvariants)를 포함하는 것을 특징으로 하고, 상기 하위변이체는 AY.1 내지 AY.28까지를 포함하는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물. According to clause 1,
The SARS-CoV-2 delta variant virus is characterized in that it includes subvariants, and the subvariants include AY.1 to AY.28, SARS-CoV-2 delta Pharmaceutical composition for preventing or treating infection by mutant viruses.
상기 조성물은 E-gene 또는 RdRp(RNA-dependent RNA polymerase)을 저해시키는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물. According to clause 1,
The composition is a pharmaceutical composition for preventing or treating infection by the SARS-CoV-2 delta variant virus, characterized in that it inhibits the E-gene or RdRp (RNA-dependent RNA polymerase).
상기 지유추출물은 물, 알코올, 또는 이들의 혼합물인 용매로 추출되는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물.According to clause 1,
A pharmaceutical composition for preventing or treating infection by SARS-CoV-2 delta variant virus, characterized in that the oil extract is extracted with a solvent that is water, alcohol, or a mixture thereof.
상기 약학적 조성물은 약제학적으로 허용 가능한 담체, 부형제 또는 희석제를 포함하는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물.According to clause 1,
The pharmaceutical composition is a pharmaceutical composition for preventing or treating infection by SARS-CoV-2 delta variant virus, characterized in that it contains a pharmaceutically acceptable carrier, excipient or diluent.
상기 약학적 조성물은 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 멸균된 수용액, 비수성용제, 유제, 동결건조제제 및 좌제로 이루어진 군으로부터 선택되는 어느 하나의 제형을 가지는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물.According to clause 1,
The pharmaceutical composition is any one dosage form selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, oral solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solvents, emulsions, freeze-dried preparations, and suppositories. A pharmaceutical composition for preventing or treating infection by SARS-CoV-2 delta variant virus, characterized in that it has.
상기 약학적 조성물은 산제, 과립제, 정제, 캡슐제 및 액체 형태로 이루어진 군으로부터 선택되는 어느 하나의 제형을 가지는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물.According to clause 1,
The pharmaceutical composition is a pharmaceutical for the prevention or treatment of infection by the SARS-CoV-2 delta variant virus, characterized in that it has any one formulation selected from the group consisting of powder, granule, tablet, capsule, and liquid form. enemy composition.
상기 지유추출물은 오이풀 (Sanguisorba officinalis L.)의 뿌리 및 긴오이풀 (Sanguisorba longifolia) 뿌리로 이루어진 그룹에서 선택된 어느하나 이상에서 추출되는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물.According to clause 1,
The oil extract is characterized in that it is extracted from one or more selected from the group consisting of the roots of Sanguisorba officinalis L. and the roots of Sanguisorba longifolia, preventing infection by the SARS-CoV-2 delta variant virus. or therapeutic pharmaceutical compositions.
상기 SARS-CoV-2 델타 변이체 바이러스는 그 하위변이체(subvariants)를 포함하는 것을 특징으로 하고, 상기 하위변이체는 AY.1 내지 AY.28까지를 포함하는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 개선용 건강기능식품 조성물. According to clause 9,
The SARS-CoV-2 delta variant virus is characterized in that it includes subvariants, and the subvariants include AY.1 to AY.28, SARS-CoV-2 delta A health functional food composition for preventing or improving infection by mutant viruses.
상기 건조된 지유를 30 내지 120℃에서 용매로 추출하는 단계; 및
상기 추출된 용액을 동결건조하여 분말을 제조하는 단계를 포함하는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물의 제조방법.drying the oil;
Extracting the dried fat with a solvent at 30 to 120°C; and
A method for producing a pharmaceutical composition for preventing or treating infection by SARS-CoV-2 delta variant virus, comprising the step of freeze-drying the extracted solution to prepare a powder.
상기 SARS-CoV-2 델타 변이체 바이러스는 그 하위변이체(subvariants)를 포함하는 것을 특징으로 하고, 상기 하위변이체는 AY.1 내지 AY.28까지를 포함하는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물의 제조방법. According to claim 11,
The SARS-CoV-2 delta variant virus is characterized in that it includes subvariants, and the subvariants include AY.1 to AY.28, SARS-CoV-2 delta Method for producing a pharmaceutical composition for preventing or treating infection by mutant viruses.
상기 용매는 물, 알코올 또는 이들의 혼합물로 이루어진 군으로부터 선택된 어느 하나 이상인 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물의 제조방법.According to claim 11,
A method for producing a pharmaceutical composition for preventing or treating infection by SARS-CoV-2 delta variant virus, wherein the solvent is at least one selected from the group consisting of water, alcohol, or mixtures thereof.
상기 약학적 조성물은 약제학적으로 허용 가능한 담체, 부형제 또는 희석제를 포함하는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물의 제조방법.According to claim 11,
A method of producing a pharmaceutical composition for preventing or treating infection by SARS-CoV-2 delta variant virus, wherein the pharmaceutical composition contains a pharmaceutically acceptable carrier, excipient, or diluent.
상기 약학적 조성물은 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 멸균된 수용액, 비수성용제, 유제, 동결건조제제 및 좌제로 이루어진 군으로부터 선택되는 어느 하나의 제형을 가지는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물의 제조방법.According to claim 11,
The pharmaceutical composition is any one dosage form selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, oral solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solvents, emulsions, freeze-dried preparations, and suppositories. A method for producing a pharmaceutical composition for preventing or treating infection by SARS-CoV-2 delta variant virus, characterized in that it has.
상기 약학적 조성물은 산제, 과립제, 정제, 캡슐제 및 액체 형태로 이루어진 군으로부터 선택되는 어느 하나의 제형을 가지는 것을 특징으로 하는, SARS-CoV-2 델타 변이체 바이러스에 의한 감염의 예방 또는 치료용 약학적 조성물의 제조방법.According to claim 11,
The pharmaceutical composition is a pharmaceutical for the prevention or treatment of infection by the SARS-CoV-2 delta variant virus, characterized in that it has any one formulation selected from the group consisting of powder, granule, tablet, capsule, and liquid form. Method for producing an enemy composition.
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| Publication Number | Publication Date |
|---|---|
| KR20240094160A true KR20240094160A (en) | 2024-06-25 |
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