KR102540814B1 - Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component - Google Patents
Composition for preventing, ameliorating or treating coronavirus infectious disease comprising herbal medicine extract as effective component Download PDFInfo
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- KR102540814B1 KR102540814B1 KR1020220140008A KR20220140008A KR102540814B1 KR 102540814 B1 KR102540814 B1 KR 102540814B1 KR 1020220140008 A KR1020220140008 A KR 1020220140008A KR 20220140008 A KR20220140008 A KR 20220140008A KR 102540814 B1 KR102540814 B1 KR 102540814B1
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Abstract
Description
본 발명은 한약재 추출물, 특히 오수유 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방, 개선 또는 치료용 조성물에 관한 것이다. The present invention relates to a composition for preventing, improving or treating a coronavirus infection comprising an extract of herbal medicine, particularly an extract of Ohsuyu as an active ingredient.
신종 제2형 중증급성호흡기증후군 코로나바이러스(SARS-CoV2)는 약 3만 개의 염기쌍으로 이루어진 단일 가닥의 양성 RNA 게놈을 가지고 있고, 바이러스 표면이 외피로 둘러싸여 있는 바이러스이다. 2019년 12월 말에 중국 우한에서 최초로 보고된 후 전 세계적으로 감염자가 폭증하였다. 상기 바이러스는 사람 사이의 전파가 매우 효율적으로 이루어져 세계보건기구에서도 전 세계에 유행이 가능한 펜데믹으로 선포하고 대응을 모색하고 있다.The new type 2 severe acute respiratory syndrome coronavirus (SARS-CoV2) has a single-stranded positive RNA genome consisting of about 30,000 base pairs, and the virus surface is surrounded by an envelope. After it was first reported in Wuhan, China at the end of December 2019, infections worldwide exploded. The virus spreads very efficiently between people, so the World Health Organization has declared it as a pandemic that can spread worldwide and is seeking countermeasures.
일반적인 코비드-19 환자는 체온상승, 기침 및 가슴 통증과 같은 비교적 심하지 않은 증상을 보이지만, 일부 환자에게서는 호흡곤란 및 폐렴과 같은 심각한 질환으로 발전되어 사망에 이르게 된다. Normal Covid-19 patients show relatively mild symptoms such as elevated body temperature, coughing and chest pain, but some patients develop serious illnesses such as shortness of breath and pneumonia, leading to death.
현재까지 코로나바이러스 감염증에 대해 공인된 치료제로는 리바비린(ribavirin), 팜시클로비르(famciclovir), 니타족사나이드(nitazoxanide), 나파모스타트(nafamostat) 및 클로로퀸(chloroquine) 등이 알려져 있으며, 이외에도 렘데시비르(remdesivir, GS-5734)와 파비피라비르(favipiravir)가 코로나바이러스 감염증 치료에 사용되고 있으나, 효과가 낮고 핵산 아날로그형 항바이러스제들의 특성상 변종바이러스의 발생율이 높아 2종 이상의 항바이러스제를 같이 적용하고 있다. 코로나바이러스 감염증에 사용되는 항바이러스제들은 대부분 RNA 폴리머라아제(polymerase) 억제능을 가지고 있지만, 렘데시비르에 대한 내성을 가지는 코로나바이러스의 일종인 마우스 간염 바이러스(Mouse hepatitis virus)가 발견되었으며, 기존의 항바이러스제의 효과가 없는 실정이다. 또한, 현재까지 개발된 항바이러스제들은 심한 부작용을 나타내고 있으므로, 그 응용에 있어서 많은 주의가 필요하다. To date, approved treatments for coronavirus infections include ribavirin, famciclovir, nitazoxanide, nafamostat, and chloroquine. In addition, remdesi Vir (remdesivir, GS-5734) and favipiravir are used for the treatment of coronavirus infections, but their effectiveness is low and the incidence of mutant viruses is high due to the nature of nucleic acid analog antiviral agents, so two or more antiviral agents are applied together. . Most of the antiviral drugs used for coronavirus infection have RNA polymerase inhibitory ability, but Mouse hepatitis virus, a type of coronavirus resistant to remdesivir, was discovered, and the existing antiviral The current situation is that there is no effect of the virus agent. In addition, since antiviral agents developed to date have severe side effects, great care is required in their application.
또한, 현재 가장 일반적인 치료 방법은 증상을 완화하는 대증요법이다. 따라서 코로나바이러스의 발생을 예방하고 치료하기 위한 감염 억제 효과가 뛰어나고 독성이 적은 새로운 항코로나바이러스제의 개발 필요성이 증가되고 있다.In addition, the most common treatment method at present is symptomatic therapy to relieve symptoms. Therefore, there is an increasing need for the development of new anti-coronavirus agents with excellent infection suppression effect and low toxicity for preventing and treating the outbreak of coronavirus.
한편, 한국등록특허 제1181216호에는 오수유 추출물, 이의 분획물 또는 퀴놀론 알칼로이드계 화합물을 포함하는 약학 조성물이 개시되어 있고, 한국공개특허 제2022-0044126호에는 돌외 추출물을 포함하는 코로나바이러스 감염 예방 또는 치료용 조성물이 개시되어 있지만, 본 발명의 한약재 추출물, 특히 오수유 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방, 개선 또는 치료용 조성물에 관해 전혀 개시된 바 없다. On the other hand, Korean Patent Registration No. 1181216 discloses a pharmaceutical composition containing an extract of Osuyu, a fraction thereof or a quinolone alkaloid-based compound, and Korean Patent Publication No. 2022-0044126 discloses a method for preventing or treating coronavirus infection containing an extract Although the composition is disclosed, there is no disclosure at all about a composition for preventing, improving or treating coronavirus infection comprising the herbal medicine extract of the present invention, particularly the ohsuyu extract as an active ingredient.
본 발명은 상기와 같은 요구에 의해 도출된 것으로, 오수유 추출물을 유효성분으로 포함하는 코로나바이러스에 대한 항바이러스용 조성물을 제공하고, 상기 오수유 추출물이 코로나바이러스 감염 및 증식을 억제하는 것을 확인함으로써, 본 발명을 완성하였다.The present invention has been derived from the above needs, by providing an antiviral composition against coronavirus containing ohsuyu extract as an active ingredient, and confirming that the ohsuyu extract inhibits coronavirus infection and proliferation, The invention was completed.
상기 과제를 해결하기 위하여, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스에 대한 항바이러스용 조성물을 제공한다. In order to solve the above problems, the present invention provides an antiviral composition for coronavirus containing Evodia rutaecarpa extract as an active ingredient.
또한, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방 또는 치료용 약학 조성물을 제공한다. In addition, the present invention provides a pharmaceutical composition for preventing or treating coronavirus infection comprising an extract of Evodia rutaecarpa as an active ingredient.
또한, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방 또는 개선용 건강기능식품 조성물을 제공한다. In addition, the present invention provides a health functional food composition for preventing or improving coronavirus infection comprising an extract of Evodia rutaecarpa as an active ingredient.
또한, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방 또는 개선용 의약외품 조성물을 제공한다. In addition, the present invention provides a quasi-drug composition for preventing or improving coronavirus infection comprising an extract of Evodia rutaecarpa as an active ingredient.
또한, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방 또는 개선용 화장료 조성물을 제공한다. In addition, the present invention provides a cosmetic composition for preventing or improving coronavirus infection comprising an extract of Evodia rutaecarpa as an active ingredient.
또한, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방 또는 개선용 사료 첨가제를 제공한다.In addition, the present invention provides a feed additive for preventing or improving coronavirus infection comprising an extract of Evodia rutaecarpa as an active ingredient.
본 발명은 오수유 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방, 개선 또는 치료용 조성물에 관한 것으로, 오수유 추출물은 코로나바이러스 감염으로부터 세포를 보호하는 효과가 있고, 세포 내 바이러스의 복제 및 바이러스의 세포 내 감염을 억제하는 효과가 있다.The present invention relates to a composition for preventing, ameliorating or treating a coronavirus infection comprising an extract of ohsuyu as an active ingredient, wherein the extract of ohsuyu is effective in protecting cells from coronavirus infection, replication of the virus in cells and cells of the virus It has the effect of suppressing my infection.
도 1은 CPE(Cytopathic effect) 억제 분석으로 오수유 추출물의 SARS-CoV2에 대한 항바이러스 효과를 확인한 결과이다. (A)는 농도별 오수유 추출물 처리에 따른 SARS-CoV2에 대한 항바이러스 효과를 크리스탈 바이올렛으로 염색한 플레이트 사진이고, (B)는 이를 정량한 결과이다. NC는 정상군이고, VC는 SARS-CoV2를 처리한 대조군이다.
도 2는 오수유 추출물의 SARS-CoV2에 대한 바이러스 감염 억제 효과를 확인한 형광사진(A) 및 이를 정량한 결과(B)이다. NC는 정상군이고, VC는 SARS-CoV2를 처리한 대조군이다. *은 SARS-CoV2를 처리한 대조군(VC) 대비 SARS-CoV2 및 오수유 추출물 처리군(500㎍/mL)의 바이러스 감염이 통계적으로 유의미하게 감소하였다는 것을 의미하며, p<0.05이다.
도 3은 오수유 추출물의 SARS-CoV2에 대한 바이러스 복제 억제 효과를 확인한 결과이다. NC는 정상군이고, VC는 SARS-CoV2를 처리한 대조군이다. **은 SARS-CoV2를 처리한 대조군(VC) 대비 SARS-CoV2 및 오수유 추출물 처리군의 바이러스 복제 수가 통계적으로 유의미하게 감소하였다는 것을 의미하며, p<0.01이다.1 is a result of confirming the antiviral effect of ohsuyu extract against SARS-CoV2 by CPE (Cytopathic effect) inhibition analysis. (A) is a photograph of a plate stained with crystal violet for the antiviral effect against SARS-CoV2 according to the treatment of Osuyu extract by concentration, and (B) is the result of quantification thereof. NC is a normal group, and VC is a control group treated with SARS-CoV2.
Figure 2 is a fluorescence photograph (A) confirming the virus infection inhibitory effect on SARS-CoV2 of Osuyu extract and a result (B) of quantifying it. NC is a normal group, and VC is a control group treated with SARS-CoV2. * means that the viral infection of the SARS-CoV2 and ohsuyu extract treatment group (500 μg/mL) was statistically significantly reduced compared to the control group (VC) treated with SARS-CoV2, p<0.05.
Figure 3 is the result of confirming the virus replication inhibitory effect on SARS-CoV2 of ohsuyu extract. NC is a normal group, and VC is a control group treated with SARS-CoV2. ** means that the number of viral copies of the SARS-CoV2 and Osuyu extract treatment group decreased statistically significantly compared to the control group (VC) treated with SARS-CoV2, p<0.01.
본 발명의 목적을 달성하기 위하여, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스에 대한 항바이러스용 조성물을 제공한다. In order to achieve the object of the present invention, the present invention provides an antiviral composition for coronavirus comprising Evodia rutaecarpa extract as an active ingredient.
상기 코로나바이러스는 제2형 중증급성호흡기증후군 코로나바이러스(SARS-CoV2), 중증급성호흡기증후군 코로나바이러스(SARS CoV) 및 중동 호흡기 증후군(MERS) 코로나바이러스로 이루어진 군에서 선택된 1종 이상인 것일 수 있고, 바람직하게는 제2형 중증급성호흡기증후군 코로나바이러스(SARS-CoV2)인 것이지만, 이에 한정하는 것은 아니다. The coronavirus may be one or more selected from the group consisting of type 2 severe acute respiratory syndrome coronavirus (SARS-CoV2), severe acute respiratory syndrome coronavirus (SARS CoV) and Middle East respiratory syndrome (MERS) coronavirus, It is preferably type 2 severe acute respiratory syndrome coronavirus (SARS-CoV2), but is not limited thereto.
상기 오수유 추출물의 추출용매는 물, C1~C4의 저급 알코올 또는 이들의 혼합물인 것이 바람직하고, 더 바람직하게는 에탄올인 것이지만, 이에 한정하는 것은 아니다.The extraction solvent of the ohsuyu extract is preferably water, C 1 ~ C 4 lower alcohol or a mixture thereof, more preferably ethanol, but is not limited thereto.
상기 오수유는 오수유의 어느 부위라도 사용할 수 있고, 바람직하게는 열매를 사용한 것이지만, 이에 제한되지 않는다.The sewage oil may be used in any part of the sewage oil, preferably using fruit, but is not limited thereto.
본 발명의 오수유 추출물은 제2형 중증급성호흡기증후군 코로나바이러스의 증식을 억제하는 효과가 있다. The Osuyu extract of the present invention has the effect of inhibiting the proliferation of type 2 severe acute respiratory syndrome coronavirus.
또한, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방 또는 치료용 약학 조성물을 제공한다. In addition, the present invention provides a pharmaceutical composition for preventing or treating coronavirus infection comprising an extract of Evodia rutaecarpa as an active ingredient.
본 발명에 따른 상기 약학 조성물은 각각 통상의 방법에 따라 캡슐제, 산제, 과립제, 정제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. The pharmaceutical composition according to the present invention is formulated according to conventional methods into oral formulations such as capsules, powders, granules, tablets, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injection solutions. can
본 발명에 따른 상기 약학 조성물은 약학적으로 허용 가능한 담체, 부형제 또는 희석제를 더 포함할 수 있다. The pharmaceutical composition according to the present invention may further include a pharmaceutically acceptable carrier, excipient or diluent.
본 발명의 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 포함한 다양한 화합물 혹은 혼합물을 들 수 있다. Carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate , cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and various compounds or mixtures including mineral oil and the like.
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 약학 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트, 수크로스 또는 락토오스, 젤라틴 등을 섞어 조제된다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당하는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔, 마크로골, 트윈 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include at least one excipient in the pharmaceutical composition, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc. is prepared by mixing In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, solutions for oral use, emulsions, syrups, etc., and various excipients such as wetting agents, sweeteners, aromatics, preservatives, etc. may be included in addition to water and liquid paraffin, which are commonly used simple diluents. . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, Witepsol, Macrogol, Tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used.
본 발명의 약학 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다.A suitable dosage of the pharmaceutical composition of the present invention may be prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, sex, morbid condition, food, administration time, administration route, excretion rate and reaction sensitivity. can
본 발명의 약학 조성물은 경구 또는 비경구로 투여할 수 있으며, 비경구투여의 경우, 피부에 국소적으로 도포, 정맥 내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있다.The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered by topical application to the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, and the like.
또한, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방 또는 개선용 건강기능식품 조성물을 제공한다. In addition, the present invention provides a health functional food composition for preventing or improving coronavirus infection comprising an extract of Evodia rutaecarpa as an active ingredient.
상기 조성물은 분말, 과립, 환, 정제, 캡슐, 캔디, 시럽 및 음료 중에서 선택된 어느 하나의 제형으로 제조될 수 있지만, 이에 한정하는 것은 아니다. The composition may be prepared in any one formulation selected from powder, granule, pill, tablet, capsule, candy, syrup and beverage, but is not limited thereto.
본 발명의 건강기능식품 조성물을 식품첨가물로 사용하는 경우, 상기 건강기능식품 조성물을 그대로 첨가하거나 다른 식품 또는 식품성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 양은 그의 사용 목적(예방 또는 개선)에 따라 적절하게 사용될 수 있다. 일반적으로, 식품 또는 음료의 제조시 본 발명의 건강기능식품 조성물은 총 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 그러나 건강을 목적으로 하는 장기간의 섭취인 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로 사용될 수 있다.When using the health functional food composition of the present invention as a food additive, the health functional food composition may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to conventional methods. The amount of the active ingredient can be appropriately used depending on the purpose of its use (prevention or improvement). In general, when preparing food or beverage, the health functional food composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the total amount of raw materials. However, in the case of long-term intake for health purposes, the amount may be less than 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 종류에 특별한 제한은 없다. 상기 건강기능식품 조성물을 첨가할 수 있는 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the type of health functional food. Examples of foods to which the functional food composition may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea There are drinks, alcoholic beverages, and vitamin complexes, and includes all health foods in a conventional sense.
또한, 본 발명의 건강기능식품 조성물은 식품, 특히 기능성 식품으로 제조될 수 있다. 본 발명의 기능성 식품은 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소 및 조미제를 포함한다. 예컨대, 드링크제로 제조되는 경우에는 유효성분 이외에 천연 탄수화물 또는 향미제를 추가 성분으로서 포함할 수 있다. 상기 천연 탄수화물은 모노사카라이드(예컨대, 글루코오스, 프럭토오스 등), 디사카라이드(예컨대, 말토스, 수크로스 등), 올리고당, 폴리사카라이드(예컨대, 덱스트린, 시클로덱스트린 등) 또는 당알코올(예컨대, 자일리톨, 소르비톨, 에리쓰리톨 등)인 것이 바람직하다. 상기 향미제는 천연 향미제(예컨대, 타우마틴, 스테비아 추출물 등)와 합성 향미제(예컨대, 사카린, 아스파르탐 등)를 이용할 수 있다.In addition, the health functional food composition of the present invention can be made into food, particularly functional food. The functional food of the present invention includes components commonly added during food preparation, and includes, for example, proteins, carbohydrates, fats, nutrients, and seasonings. For example, when prepared as a drink, natural carbohydrates or flavoring agents may be included as additional ingredients in addition to active ingredients. The natural carbohydrate is a monosaccharide (eg, glucose, fructose, etc.), a disaccharide (eg, maltose, sucrose, etc.), an oligosaccharide, a polysaccharide (eg, dextrin, cyclodextrin, etc.) or a sugar alcohol (eg, For example, xylitol, sorbitol, erythritol, etc.) is preferable. As the flavoring agent, natural flavoring agents (eg, thaumatin, stevia extract, etc.) and synthetic flavoring agents (eg, saccharin, aspartame, etc.) may be used.
상기 건강기능식품 조성물 이외에 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 더 함유할 수 있다. 이러한 상기 첨가되는 성분의 비율은 크게 중요하진 않지만 본 발명의 건강기능식품 조성물 100 중량부에 대하여, 0.01 내지 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the health functional food composition, various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonic acid It may further contain a carbonation agent used in beverages and the like. The ratio of the components to be added is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight based on 100 parts by weight of the health functional food composition of the present invention.
또한, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방 또는 개선용 의약외품 조성물을 제공한다. In addition, the present invention provides a quasi-drug composition for preventing or improving coronavirus infection comprising an extract of Evodia rutaecarpa as an active ingredient.
상기 의약외품은 피부외용제 및 개인위생용품을 포함할 수 있다. 예를 들어, 소독청결제, 샤워폼, 가그린, 물티슈, 세제비누, 핸드워시, 또는 연고제일 수 있으나 이에 제한되지는 않는다.The quasi-drugs may include external skin preparations and personal hygiene products. For example, it may be a disinfectant cleanser, shower foam, gargreen, wet tissue, detergent soap, hand wash, or ointment, but is not limited thereto.
본 발명에 따른 상기 의약외품 조성물을 의약외품 첨가물로 사용할 경우, 상기 조성물을 그대로 첨가하거나 다른 의약외품 또는 의약외품 성분과 함께 사용 할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효성분의 혼합량은 사용 목적에 따라 적합하게 결정될 수 있다.When the quasi-drug composition according to the present invention is used as a quasi-drug additive, the composition may be added as it is or used together with other quasi-drugs or quasi-drug ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of use.
본 발명의 의약외품 조성물은 일 예로, 일반적인 유화 제형 및 가용화 제형의 형태로 제조된 것일 수 있다. 예를 들어, 로션 등과 같은 유액, 크림, 연고, 스프레이, 오일젤, 젤, 오일, 에어로졸과 같은 제형을 가질 수 있으나, 본 발명의 코로나바이러스 감염증의 예방 또는 개선 효과를 나타내는 것이라면 제한되지 않고 사용할 수 있다. The quasi-drug composition of the present invention may be prepared in the form of, for example, a general emulsified formulation and a solubilized formulation. For example, it may have formulations such as emulsions, creams, ointments, sprays, oil gels, gels, oils, and aerosols such as lotions, but it may be used without limitation as long as it exhibits the effect of preventing or improving coronavirus infection of the present invention. there is.
또한, 상기 의약외품 조성물은 각각의 제형에 일반적으로 의약외품 조성물에 배합되는 유분, 물, 계면활성제, 보습제, 탄소수 1 내지 4의 저급 알코올, 증점제, 킬레이트제, 색소, 방부제 또는 향료 등을 필요에 따라 적절히 배합하여 사용할 수 있다.In addition, the quasi-drug composition may appropriately contain oil, water, a surfactant, a moisturizer, a lower alcohol having 1 to 4 carbon atoms, a thickener, a chelating agent, a colorant, a preservative, or a flavoring agent, which are generally formulated in quasi-drug compositions, in each dosage form. Can be used in combination.
또한, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방 또는 개선용 화장료 조성물을 제공한다. In addition, the present invention provides a cosmetic composition for preventing or improving coronavirus infection comprising an extract of Evodia rutaecarpa as an active ingredient.
본 발명의 화장료 조성물은 상기 추출물 이외에 화장료 조성물에 통상적으로 이용되는 성분들이 포함되며, 예컨대 항산화제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 그리고 담체를 포함한다.The cosmetic composition of the present invention includes components commonly used in cosmetic compositions in addition to the extract, for example, antioxidants, stabilizers, solubilizers, vitamins, pigments and flavoring agents, and carriers.
본 발명의 화장료 조성물은 당 업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어, 용액, 현탁액, 유탁액, 페이스트, 겔, 크림, 로션, 파우더, 비누, 계면활성제-함유 클렌징, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션 및 스프레이 등으로 제형화될 수 있으나, 이에 한정되는 것은 아니다. 보다 상세하게는, 유연 화장수(스킨), 영양 화장수(밀크로션), 영양 크림, 맛사지 크림, 에센스, 아이크림, 클렌징 크림, 클렌징 포옴, 클렌징 워터, 샴푸, 팩, 스프레이 또는 파우더의 제형으로 제조될 수 있다.The cosmetic composition of the present invention can be prepared in any formulation conventionally prepared in the art, for example, a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing , It may be formulated as an oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, it may be formulated into a flexible lotion (skin), nourishing lotion (milk lotion), nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, shampoo, pack, spray or powder. can
본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성 유, 식물성 유, 왁스, 파라핀, 전분, 트라가칸타, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide, etc. are used as carrier components. It can be.
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additional chlorofluorohydrocarbon, propane / May contain a propellant such as butane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butyl glycol oil, fatty acid esters of glycerol, polyethylene glycol or sorbitan.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소 결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라가칸타 등이 이용될 수 있다.When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Star cellulose, aluminum metahydroxide, bentonite, agar or tragacantha and the like may be used.
본 발명의 제형이 계면-활성제 함유 클렌징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is surfactant-containing cleansing, as carrier components, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
또한, 본 발명은 오수유(Evodia rutaecarpa) 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방 또는 개선용 사료 첨가제를 제공한다.In addition, the present invention provides a feed additive for preventing or improving coronavirus infection comprising an extract of Evodia rutaecarpa as an active ingredient.
본 발명의 사료 첨가제는 사료관리법상의 보조사료에 해당한다. 본 발명에서 용어 '사료'는 동물이 먹고, 섭취하며, 소화시키기 위한 또는 이에 적당한 임의의 천연 또는 인공 규정식, 한끼식 등 또는 상기 한끼식의 성분을 의미할 수 있다. 상기 사료의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용되는 사료를 사용할 수 있다. 상기 사료의 비제한적인 예로는, 곡물류, 근과류, 식품 가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류 또는 곡물 부산물류 등과 같은 식물성 사료; 단백질류, 무기물류, 유지류, 광물성류, 유지류, 단세포 단백질류, 동물성 플랑크톤류 또는 음식물 등과 같은 동물성 사료를 들 수 있다. 이들은 단독으로 사용되거나 2종 이상을 혼합하여 사용될 수 있다.The feed additive of the present invention corresponds to supplementary feed under the Feed Management Act. In the present invention, the term 'feed' may refer to any natural or artificial diet, one meal, etc., or a component of the one meal meal, suitable for or suitable for consumption by animals. The type of feed is not particularly limited, and feeds commonly used in the art may be used. Non-limiting examples of the feed include vegetable feeds such as grains, root fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal or grain by-products; Animal feed such as proteins, inorganic materials, oils, mineral oils, oils, single cell proteins, zooplankton, or food may be mentioned. These may be used alone or in combination of two or more.
이하, 제조예 및 실시예를 이용하여 본 발명을 더욱 상세하게 설명하고자 한다. 이들 제조예 및 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 범위가 이들에 의해 제한되지 않는다는 것은 당해 기술분야에서 통상의 지식을 가진 자에게 있어 자명한 것이다. Hereinafter, the present invention will be described in more detail using preparation examples and examples. These Preparation Examples and Examples are only for explaining the present invention in more detail, and it is obvious to those skilled in the art that the scope of the present invention is not limited thereto.
제조예 1. 오수유 추출물의 제조Preparation Example 1. Preparation of ohsuyu extract
오수유는 (주)옴니허브로부터 규격품을 구입하였으며, 오수유 추출물은 구체적으로, 오수유 건조 원물 1 중량부에 대하여 10 중량부의 30%(v/v) 에탄올을 첨가한 후, 3시간 동안 환류 추출한 다음 거름망(추출포)에 여과한 후 53㎛ 필터에 통과시킨 통과물을 감압 농축한 다음 동결건조하여 제조하였다.Ohsuyu was purchased as a standard product from OmniHub Co., Ltd., and the Ohsuyu extract was specifically, 10 parts by weight of 30% (v/v) ethanol was added to 1 part by weight of the dried raw material of Ohsuyu, followed by reflux extraction for 3 hours and then through a sieve. After filtering through (extraction cloth), the passage through a 53 μm filter was concentrated under reduced pressure and then lyophilized to prepare.
실시예 1. 항바이러스 활성평가: CPE 저해 어세이 시스템 구축 Example 1. Evaluation of antiviral activity: CPE inhibition assay system construction
96웰 플레이트에 Vero E6 세포를 배양한 후, SARS-CoV2를 m.o.i 0.01로 접종하였다. 접종 후, 상기 제조예 1의 오수유 추출물을 2%(v/v) FBS 및 1%(v/v) 페니실린-스트렙토마이신이 포함된 DMEM으로 희석하여 3일 동안 배양하였다. 배양 후, 세포 배양액을 제거한 다음 메탄올:아세톤이 1:1 부피비로 혼합된 용액을 처리한 다음 실온에서 10분 동안 고정하였다. 이후, 용액을 제거하고, 0.4%(w/v) 크리스탈 바이올렛(crystal violet)을 각 웰에 첨가한 다음 10분 동안 실온에서 염색한 후, 용액을 모두 제거하고 건조하였다. 건조 후, 메탄올:아세트산을 1:1 부피비로 혼합한 후, 3차 증류수로 5배 희석한 용액을 각 웰에 100㎕씩 첨가한 후 2시간 동안 크리스탈 바이올렛을 추출한 다음 550nm에서 흡광도를 측정하였다. After culturing Vero E6 cells in a 96-well plate, SARS-CoV2 was inoculated with m.o.i 0.01. After inoculation, the Osuyu extract of Preparation Example 1 was diluted with DMEM containing 2% (v/v) FBS and 1% (v/v) penicillin-streptomycin and cultured for 3 days. After incubation, the cell culture medium was removed and treated with a mixed solution of methanol:acetone in a volume ratio of 1:1, followed by fixation at room temperature for 10 minutes. Thereafter, the solution was removed, and 0.4% (w/v) crystal violet was added to each well, followed by staining at room temperature for 10 minutes, and then the solution was removed and dried. After drying, methanol:acetic acid was mixed at a volume ratio of 1:1, and 100 μl of a 5-fold diluted solution with tertiary distilled water was added to each well, crystal violet was extracted for 2 hours, and absorbance was measured at 550 nm.
그 결과, 도 1에 개시된 바와 같이 본 발명의 오수유 추출물은 SARS-CoV2의 증식을 효과적으로 억제하여, SARS-CoV2 바이러스로부터 세포를 보호하는 항바이러스 효과가 우수하였다.As a result, as shown in FIG. 1, the ohsuyu extract of the present invention effectively inhibits the proliferation of SARS-CoV2, and has excellent antiviral effect of protecting cells from SARS-CoV2 virus.
실시예 2. 오수유 추출물의 바이러스 감염 억제 효과 확인 Example 2. Confirmation of virus infection inhibitory effect of Ohsuyu extract
오수유 추출물을 이용하여 SARS-CoV2 바이러스 감염 억제 효과를 면역형광분석법으로 확인하였다. 구체적으로, Vero E6 세포를 1×104 세포/웰로 플레이트에 분주하고, 농도별 제조예 1의 시료를 처리한 후, 2%(v/v) FBS 및 1%(v/v) 항생제가 포함된 DMEM으로 1000배 희석한 SARS-CoV2를 처리한 다음 24시간 동안 배양하였다. 배양 후, 4%(v/v) 포름알데히드(formaldehyde) 용액으로 세포를 고정한 다음 2000배 희석한 1차 항체(Nucleocapsid 단백질)와 반응시킨 후, 200배 희석한 2차 항체와 반응시켰다. 반응 후, 세포를 형광현미경으로 관찰하였고, 형광강도를 분석하였다. The inhibitory effect of SARS-CoV2 virus infection was confirmed by immunofluorescence analysis using Ohsuyu extract. Specifically, after the Vero E6 cells were dispensed into a plate at 1×10 4 cells/well, and the sample of Preparation Example 1 was treated by concentration, 2% (v/v) FBS and 1% (v/v) antibiotics were included. 1000-fold diluted SARS-CoV2 was treated with DMEM and cultured for 24 hours. After culturing, the cells were fixed with a 4% (v/v) formaldehyde solution, reacted with a 2000-fold diluted primary antibody (Nucleocapsid protein), and then reacted with a 200-fold diluted secondary antibody. After the reaction, the cells were observed under a fluorescence microscope and the fluorescence intensity was analyzed.
그 결과, 도 2에 개시된 바와 같이 오수유 추출물 처리에 의해 SARS-CoV2 바이러스의 세포 내 감염이 효과적으로 억제되었다.As a result, intracellular infection of the SARS-CoV2 virus was effectively inhibited by treatment with the ohsuyu extract, as shown in FIG. 2 .
실시예 3. 오수유 추출물의 바이러스 복제 억제 효과 확인 Example 3. Confirmation of virus replication inhibitory effect of Ohsuyu extract
오수유 추출물의 바이러스 복제 억제 효과를 qPCR로 확인하였다. 구체적으로, 96웰 플레이트에 Vero E6 세포를 배양한 후, SARS-CoV2를 m.o.i 0.01로 접종하고, 제조예 1의 시료를 처리한 후, 24시간 동안 배양하였다. 배양 후, 바이오니아사의 AccuPrep Viral RNA Extraction kit를 사용하여 세포 밖으로 방출된 바이러스 RNA를 추출하였다. 이어서 토요보사의 ReverTra Ace qPCR RT kit를 사용하여 cDNA를 합성한 다음 스파이크단백질의 RBD에 대한 특이적인 프라이머로 PCR을 수행하고 바이러스 RNA 복제 수(viral RNA copy number)를 스파이크 단백질 유전자 플라스미드 표준 시료를 이용해 계산하였다. The virus replication inhibitory effect of Ohsuyu extract was confirmed by qPCR. Specifically, after culturing Vero E6 cells in a 96-well plate, SARS-CoV2 was inoculated with m.o.i 0.01, treated with the sample of Preparation Example 1, and cultured for 24 hours. After culturing, viral RNA released outside the cell was extracted using AccuPrep Viral RNA Extraction kit from Bioneer. Subsequently, cDNA was synthesized using Toyobo's ReverTra Ace qPCR RT kit, PCR was performed with primers specific for the RBD of spike protein, and viral RNA copy number was measured using spike protein gene plasmid standard samples. Calculated.
그 결과, 도 3에 개시된 바와 같이 오수유 추출물은 SARS-CoV2 바이러스의 복제를 억제하는 효과가 우수하였다. As a result, as shown in FIG. 3, the extract of Ohsuyu was excellent in inhibiting the replication of SARS-CoV2 virus.
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US20210330705A1 (en) * | 2020-04-23 | 2021-10-28 | Brain Cancer Research Institute | Tolerogenic dendritic cells for treatment of acute respiratory distress syndrome |
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JPH0625003A (en) * | 1992-04-27 | 1994-02-01 | Showa Shell Sekiyu Kk | Galenical drug-containing antiviral agent |
US20210330705A1 (en) * | 2020-04-23 | 2021-10-28 | Brain Cancer Research Institute | Tolerogenic dendritic cells for treatment of acute respiratory distress syndrome |
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