KR101886337B1 - Antiviral composition for influenza virus comprising lactobacillus plantarum dsr m2 as an active material - Google Patents
Antiviral composition for influenza virus comprising lactobacillus plantarum dsr m2 as an active material Download PDFInfo
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- KR101886337B1 KR101886337B1 KR1020160123713A KR20160123713A KR101886337B1 KR 101886337 B1 KR101886337 B1 KR 101886337B1 KR 1020160123713 A KR1020160123713 A KR 1020160123713A KR 20160123713 A KR20160123713 A KR 20160123713A KR 101886337 B1 KR101886337 B1 KR 101886337B1
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- KR
- South Korea
- Prior art keywords
- lactobacillus plantarum
- influenza
- composition
- influenza virus
- active ingredient
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Abstract
본 발명은 락토바실러스 플란타륨을 유효성분으로 함유하는 인플루엔자 바이러스에 대한 항바이러스용 약학 조성물에 관한 것이다. 보다 구체적으로는, 본 발명의 락토바실러스 플란타륨 DSR M2는 인플루엔자 바이러스에 대한 항바이러스 활성이 우수하므로, 이를 유효성분으로 함유하는 약학적 조성물은 인플루엔자 바이러스 감염에 의해 발병되는 독감, 감기, 인후염, 기관지염, 폐렴, 조류독감, 돼지독감, 염소독감 등의 예방 또는 치료용으로 유용하게 사용될 수 있다.
또한, 상기의 항바이러스 활성을 나타내는 락토바실러스 플란타륨 DSR M2는 음료, 발효식품, 건강기능식품 등과 식품 조성물, 식품첨가제 조성물, 사료 조성물 또는 사료첨가제 조성물 등에 유용하게 활용될 수 있다.The present invention relates to a pharmaceutical composition for an antiviral against influenza virus containing Lactobacillus plantarum as an active ingredient. More specifically, the Lactobacillus plantarum DSR M2 of the present invention is excellent in antiviral activity against influenza virus, and therefore, the pharmaceutical composition containing the same as an active ingredient can be used for influenza virus, cold, sore throat, Bronchitis, pneumonia, avian influenza, swine flu, chlorophyll, and the like.
Lactobacillus plantarum DSR M2, which exhibits the antiviral activity described above, may be usefully used in beverage, fermented food, health functional food, and the like, food composition, food additive composition, feed composition or feed additive composition.
Description
본 발명은 락토바실러스 플란타륨을 유효성분으로 함유하는 인플루엔자 바이러스에 대한 항바이러스용 약학 조성물에 관한 것이다. 또한, 본 발명은 락토바실러스 플란타륨을 유효성분으로 함유하는 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 식품 조성물, 사료 조성물 또는 세정용 조성물 등에 관한 것이다.
The present invention relates to a pharmaceutical composition for an antiviral against influenza virus containing Lactobacillus plantarum as an active ingredient. The present invention also relates to a food composition, a feed composition or a cleaning composition for preventing or ameliorating an influenza virus infectious disease containing Lactobacillus plentarium as an active ingredient.
인플루엔자 바이러스는 급성 호흡기감염질환인 독감의 원인체로, 공중보건학적으로 매우 중요하게 여겨지는 병원체 중의 하나이다.
Influenza virus is the causative agent of the flu, an acute respiratory infectious disease, and one of the pathogens considered to be very important in public health.
H1N1과 H3N2 아형의 A형 인플루엔자 바이러스와 Victoria와 Yamagata lineage의 B형 인플루엔자 바이러스로 구성되는 계절성 인플루엔자 바이러스(seasonal influenza virus)는 매년 겨울철 유행하며 사람들에게 큰 피해를 입히고 있다. 세계보건기구(WHO)에 따르면, 매년 전세계적으로 약 3백만~5백만 명의 사람들이 계절성 인플루엔자 바이러스에 감염되어 심각한 병증을 겪고, 그 중 약 25만~50만 명의 사람들이 사망하는 것으로 알려져 있다.
The seasonal influenza virus, which consists of the H1N1 and H3N2 subtypes of influenza A virus and the influenza B virus of Victoria and Yamagata lineage, is in winter every year and is causing great damage to people. According to the World Health Organization (WHO), about 3 million to 5 million people worldwide are infected with the seasonal influenza virus each year and suffer from serious illness, of which about 250,000 to 500,000 people are known to die.
인플루엔자 바이러스의 대유행(pandemic)은 더욱 큰 피해를 초래한다. 1918년 발생한 인플루엔자 바이러스 대유행 시 약 5천만 명의 사람이 사망하였으며 1957년과 1968년에 발생한 인플루엔자 바이러스 대유행 시에는 의해 약 백만 명의 사람이 사망한 것으로 알려져 있다. 인류는 지난 2009년 신종 인플루엔자 바이러스에 의해 발생한 대유행 시에도 심각한 인적 피해와 경제적 피해 그리고 사회적 혼란을 경험한 바 있었다.
The pandemic of influenza viruses causes more damage. The influenza virus pandemic, which occurred in 1918, killed some 50 million people, and the influenza virus pandemic, which occurred in 1957 and 1968, is known to have killed about 1 million people. Humans experienced severe personal injury, economic damage and social disruption in the pandemic caused by the 2009 influenza virus.
조류인플루엔자 바이러스(avian influenza virus) 역시 심각한 위협으로 여겨지고 있다. 현재까지도 조류인플루엔자 바이러스의 지속적인 사람감염 사례가 보고되고 있다. 특히 고병원성 H5N1 조류인플루엔자 바이러스의 경우 약 59%, H7N9 조류인플루엔자 바이러스의 경우 약 32%의 높은 치사율을 나타내는 것으로 분석되고 있어 WHO에서 예의주시하고 있는 상황이다.
Avian influenza virus is also considered a serious threat. Until now, there have been reports of persistent human infections of avian influenza virus. Especially, 59% of the highly pathogenic H5N1 avian influenza virus and 32% of the H7N9 avian influenza virus have been analyzed, which is closely monitored by WHO.
이러한 인플루엔자 바이러스를 예방하기 위한 가장 효과적인 방법은 백신접종으로 알려져 있지만 백신만으로 인플루엔자 바이러스에 의한 피해를 조절하기에는 한계가 있다. 현재 계절성 인플루엔자 바이러스에 대한 백신을 접종하고 있음에도 불구하고 전세계적으로 매년 25만~50만 명의 사망자가 발행하고 있다.
Although the most effective way to prevent such influenza viruses is known as vaccination, only the vaccine has a limitation in controlling the damage caused by the influenza virus. Despite vaccination against seasonal influenza virus, there are 250,000 to 500,000 deaths worldwide each year.
인플루엔자 백신의 경우, 인플루엔자 바이러스가 갖는 항원성 변이 특성 때문에 그 해 겨울에 유행할 바이러스를 연초에 예측한 뒤 이에 대한 백신을 생산하는 생산체계에 따라 제작된다. 따라서 제작된 백신이 그 해 겨울 유행하는 인플루엔자 바이러스의 항원과 일치하지 않는 상황이 발생 할 수 있으며, 이러한 경우 사람을 인플루엔자 바이러스 감염으로부터 효과적으로 보호하지 못할 수도 있다. 또한 예측하지 못한 시기에 신종인플루엔자 바이러스가 갑작스럽게 유행 할 경우 백신으로는 신속한 초기대응이 어렵다.
Influenza vaccines are produced according to a production system that anticipates viruses that will be outbred in winter due to the nature of the antigenic variation of influenza viruses, and then produces vaccines against them. Therefore, there may be cases where the vaccine produced does not coincide with the influenza virus antigens of the winter season, and it may not protect people effectively against influenza virus infection. Also, if the swine flu virus is suddenly outbreak at an unpredictable time, it is difficult to respond quickly to the vaccine.
항바이러스제의 사용은 이러한 백신의 한계점을 극복할 수 있었다. 실제로 지난 2009년 발생한 신종인플루엔자 바이러스 대유행 시, 충분한 도즈(dose)의 백신이 준비되기 전, 인플루엔자 바이러스 표면 당단백질 중 하나인 neuraminidase(NA)를 억제하는 항바이러스제(NA inhibitor, NAI)인 oseltamivir(상품명 Tamiflu®)가 효과적인 신종 인플루엔자 바이러스 조절 수단으로 널리 처방되었다. 최근 연구에 따르면, 2009년 당시 oseltamivir의 처방은 신종인플루엔자 바이러스로부터 효과적으로 사람들을 보호한 것으로 분석되었다.The use of antiviral agents could overcome the limitations of these vaccines. In fact, oseltamivir (NA inhibitor, NAI), which inhibits neuraminidase (NA), one of the surface glycoproteins of influenza virus, before the preparation of a sufficient dose vaccine in the pandemic of the new influenza virus in 2009, Tamiflu ® ) has been widely prescribed as an effective swine influenza virus control. According to a recent study, oseltamivir's prescription at the time of 2009 was found to effectively protect people from the swine influenza virus.
위와 같은 항바이러스제의 장점에도 불구하고, 지속적인 항바이러스제의 사용은 항바이러스제 내성 인플루엔자 바이러스의 출현을 유도할 수 있다. 실제로 지난 2007~2009년 사이 NAI인 oseltamivir에 대한 내성을 획득한 H1N1 아형의 계절성 인플루엔자 바이러스(A/Birsbane/59/2007)가 전세계적으로 출현하여 유행하였다. 이와 같은 상황이 현재 유행하고 있는 인플루엔자 바이러스에서도 나타날 수 있는 가능성이 높은 것으로 여겨지고 있으며, 실제로 국내(질병관리본부)에서 oseltamivir에 내성을 갖는 신종인플루엔자 바이러스 분리 사례를 보고한 바 있다. 또한 B형 인플루엔자 바이러스의 경우 A형 인플루엔자 바이러스에 비해 상대적으로 NAI에 대한 감수성이 낮은 것으로 알려져 있다.
Despite the advantages of such antiviral agents, the continued use of antiviral agents can lead to the emergence of antiviral resistant influenza viruses. In fact, the seasonal influenza A (H1N1) influenza virus (A / Birsbane / 59/2007), which acquired resistance to the NAI, oseltamivir, between 2007 and 2009, became popular worldwide. This situation is considered to be highly likely to occur in the current influenza virus, and in fact, the domestic (Disease Control Headquarters) has reported a case of isolating a new influenza virus resistant to oseltamivir. It is also known that influenza B virus is less susceptible to NAI than influenza A virus.
따라서 항바이러스제에 내성을 갖는 바이러스의 발생 시 효과적으로 사용할 수 있는 새로운 항바이러스제 또는 항바이러스제와 함께 사용하였을 때 상승효과를 보일 수 있는 보조제의 개발이 매우 시급한 상황이다. 새로운 항바이러스제 또는 항바이러스 보조제의 개발은 큰 경제적 이익을 창출할 수 있으므로, 현재 전세계의 많은 연구진과 제약회사에서 새로운 항바이러스제 개발에 박차를 가하고 있다.
Therefore, it is very urgent to develop an adjuvant which can exhibit a synergistic effect when it is used together with a new antiviral agent or antiviral agent which can be effectively used when a virus having resistance to an antiviral agent is generated. The development of new antiviral or antiviral adjuvants can create great economic benefits, and many researchers and pharmaceutical companies around the world are now spurring the development of new antiviral drugs.
우리나라 역시 국내 기술로 새로운 항바이러스제를 개발해야 할 필요성이 매우 높게 요구되고 있으며, 항바이러스제 개발에 대한 국내 고유의 기술을 축적하고 해외 의존도를 낮추기 위해서 우리나라만의 전통 약제나 식품에서 새로운 항바이러스제 후보물질을 탐색ㆍ발굴하는 연구가 시급히 요구되고 있다.
In Korea, too, there is a great need to develop new antiviral drugs with domestic technology. In order to accumulate technologies unique to domestic antiviral drug development and to reduce dependence on foreign countries, There is an urgent need for research for exploring and exploring.
최근에 발표된 다수의 연구논문에 따르면, 유산균이 인플루엔자 바이러스 감염을 억제하고 인플루엔자 백신의 면역원성을 높이는 기능을 하는 것으로 밝혀졌다. 이러한 관점에서 볼 때, 풍부한 유산균을 갖고 있는 우리나라의 대표적인 발효식품인 김치 및 김치 유래 유산균은 항바이러스 효능을 갖는 의약품 보조제로 개발될 수 있는 높은 가능성을 갖고 있다.
According to a number of recently published research papers, lactic acid bacteria have been shown to inhibit influenza virus infection and to enhance the immunogenicity of influenza vaccines. From this point of view, kimchi and kimchi-derived lactic acid bacteria, which are representative fermented foods of Korea, which have abundant lactic acid bacteria, have a high possibility of being developed as a pharmaceutical adjuvant having antiviral efficacy.
따라서 항바이러스 효능을 나타내는 의약품 보조제로서의 가능성이 매우 높은 김치 및 김치 유래 유산균을 이용하여 새로운 항바이러스 물질을 개발한다면, 원료 및 기술에 대한 해외 의존도를 크게 낮출 수 있고 농식품 분야에 있어 경제적으로도 큰 이익을 창출 할 수 있을 것으로 사료된다. 일례로, 2009년 대유행 시 로슈(Roche)사는 Tamiflu®의 판매로 약 9억달러의 수익을 얻은 것으로 알려져 있다.
Therefore, if new antiviral substances are developed by using lactic acid bacteria derived from kimchi and kimchi, which are highly likely to be antibiotic-effective drugs, foreign dependence on raw materials and technology can be greatly reduced and economic benefits Of the total population. For example, in 2009, Roche was reported to have earned about $ 900 million in sales of Tamiflu ® .
궁극적으로, 인플루엔자 바이러스를 효과적으로 억제할 수 있는 김치 유산균을 개발한다면, 인플루엔자 바이러스 대유행과 같은 상황 발생 시 기본 치료제의 신속한 확보가 불가능한 상황하에서 신속하게 우리국민을 인플루엔자 바이러스의 위험으로부터 보호할 수 있으리라 사료된다.
Ultimately, if Kimchi lactic acid bacteria, which can effectively inhibit influenza viruses, are developed, it will be possible to protect the Korean people from the risk of influenza virus rapidly in situations where it is not possible to quickly obtain basic treatment agents in the event of a pandemic influenza virus .
이에 본 출원의 발명자들은 인플루엔자 바이러스를 효과적으로 억제 할 수 있는 유산균에 대해 연구하던 중, 락토바실러스 플란타륨DSR M2 유산균이 인플루엔자 바이러스의 성장을 억제하는 효과가 우수함을 확인하였다.
Accordingly, the inventors of the present application confirmed that Lactobacillus plantarum DSR M2 lactic acid bacteria inhibits the growth of influenza virus while studying lactic acid bacteria that can effectively inhibit influenza virus.
본 발명은 식물성 유산균을 유효성분으로 하는 인플루엔자 바이러스에 대한 항바이러스용 약학 조성물을 제공하기 위한 것이다.The present invention is to provide an antiviral pharmaceutical composition for influenza virus comprising as an active ingredient a plant-derived lactic acid bacterium.
또한, 본 발명의 다른 목적은 식물성 유산균을 유효성분으로 하는 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 식품 조성물 또는 식품 첨가제 조성물을 제공하기 위한 것이다.Another object of the present invention is to provide a food composition or food additive composition for preventing or ameliorating an influenza virus infectious disease comprising an active ingredient of a plant-derived lactic acid bacterium.
또한, 본 발명의 다른 목적은 식물성 유산균을 유효성분으로 하는 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 사료 조성물 또는 사료 첨가제 조성물을 제공하기 위한 것이다.
Another object of the present invention is to provide a feed composition or feed additive composition for preventing or ameliorating an influenza virus infectious disease comprising as an active ingredient a plant-derived lactic acid bacterium.
이에 본 발명은 바람직한 제1구현예로서, 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스에 대한 항바이러스용 약학 조성물을 제공하고자 한다.Accordingly, the present invention provides, as a first preferred embodiment, an antiviral pharmaceutical composition for influenza virus containing Lactobacillus plantarum DSR M2 [Accession No .: KFCC-11432] or a culture thereof as an active ingredient.
이때, 상기 바이러스는 A/Korea/01/2009(H1N1)의 A형 인플루엔자 바이러스일 수 있다.At this time, the virus may be an influenza A virus of A / Korea / 01/2009 (H1N1).
상기 구현예에 의한 항바이러스용 약학 조성물은 인플루엔자 바이러스 감염으로 인한 질환을 예방 또는 치료하기 위한 것일 수 있다.The pharmaceutical composition for antiviral according to the above embodiment may be one for preventing or treating a disease caused by an influenza virus infection.
또한, 상기 바이러스 감염으로 인한 질환은 독감, 감기, 인후염, 기관지염, 폐렴, 조류독감, 돼지독감 및 염소독감 중의 하나일 수 있다.In addition, the disease caused by the viral infection may be one of influenza, cold, sore throat, bronchitis, pneumonia, avian influenza, swine flu and chlorine influenza.
본 발명은 바람직한 제2구현예로서, 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 식품 조성물을 제공한다.As a second preferred embodiment of the present invention, there is provided a food composition for preventing or ameliorating an influenza virus infection disease containing Lactobacillus plantarum DSR M2 (Accession No .: KFCC-11432) or a culture thereof as an active ingredient.
본 발명은 바람직한 제3구현예로서, 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 식품 첨가제 조성물을 제공한다.The present invention provides, as a third preferred embodiment, a food additive composition for preventing or ameliorating an influenza virus infectious disease containing Lactobacillus plantarum DSR M2 [Accession No .: KFCC-11432] or a culture thereof as an active ingredient .
본 발명은 바람직한 제4구현예로서, 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 생균제 조성물을 제공한다.As a fourth preferred embodiment of the present invention, there is provided a prophylactic composition for preventing or ameliorating an influenza virus infection disease comprising Lactobacillus plantarum DSR M2 (Accession No .: KFCC-11432) or a culture thereof as an active ingredient.
본 발명은 바람직한 제5구현예로서, 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 사료 조성물을 제공한다.As a fifth preferred embodiment of the present invention, there is provided a feed composition for preventing or ameliorating an influenza virus infection disease comprising Lactobacillus plantarum DSR M2 (Accession No .: KFCC-11432) or a culture thereof as an active ingredient.
본 발명은 바람직한 제6구현예로서, 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 사료 첨가제 조성물을 제공한다.As a sixth preferred embodiment of the present invention, there is provided a feed additive composition for preventing or ameliorating an influenza virus infectious disease containing Lactobacillus plantarum DSR M2 (Accession No .: KFCC-11432) or a culture thereof as an active ingredient .
본 발명은 바람직한 제7구현예로서, 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 발효식품을 제공한다.As a seventh preferred embodiment, the present invention provides a fermented food for preventing or ameliorating an influenza virus infectious disease containing Lactobacillus plantarum DSR M2 [Accession No .: KFCC-11432] or a culture thereof as an active ingredient.
본 발명은 바람직한 제8구현예로서, 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스 소독용 또는 세정용 조성물을 제공한다.The present invention provides, as a preferable eighth embodiment, a composition for disinfection or cleaning of influenza virus containing Lactobacillus plantarum DSR M2 (Accession No .: KFCC-11432) or a culture thereof as an active ingredient.
상기 구현예에 의한 소독용 또는 세정용 조성물은 소독제, 주방세제, 세탁세제, 야채·채소 세척제 또는 손 세정제에 사용될 수 있다.
The composition for disinfection or cleaning according to the above embodiments may be used as a disinfectant, a kitchen detergent, a laundry detergent, a vegetable or vegetable detergent, or a hand cleaner.
본 발명의 락토바실러스 플란타륨 DSR M2는 인플루엔자 바이러스에 대한 항바이러스 활성이 우수하므로, 이를 유효성분으로 함유하는 약학적 조성물은 인플루엔자 바이러스 감염에 의해 발병되는 독감, 감기, 인후염, 기관지염, 폐렴, 조류독감, 돼지독감, 염소독감 등의 예방 또는 치료용으로 유용하게 사용될 수 있다. 또한, 상기의 항바이러스 활성을 나타내는 락토바실러스 플란타륨 DSR M2는 음료, 발효식품, 건강기능식품 등과 식품 조성물, 식품첨가제 조성물, 사료 조성물 또는 사료첨가제 조성물 등에 유용하게 활용될 수 있다.
Since the Lactobacillus plantarum DSR M2 of the present invention is excellent in antiviral activity against influenza virus, the pharmaceutical composition containing the same as an active ingredient can be used as an effective ingredient for preventing or treating influenza, cold, sore throat, bronchitis, Flu, swine flu, chlorine flu, and the like. Lactobacillus plantarum DSR M2, which exhibits the antiviral activity described above, may be usefully used in beverage, fermented food, health functional food, and the like, food composition, food additive composition, feed composition or feed additive composition.
도 1은 본 발명의 락토바실러스 플란타륨 DSR M2의 인플루엔자 바이러스에 대한 항바이러스 활성을 나타내는 현미경 사진이다.1 is a photomicrograph showing the antiviral activity of influenza virus of Lactobacillus plantarum DSR M2 of the present invention.
이하, 본 발명을 보다 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명의 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432P]는 김치에서 분리된 것으로, pH 2.5에서 85% 이상 생존하여 강한 내산성을 가지고, NaCl 15%(v/v)에서 90% 이상 생존하여 강한 내염성을 가지며, 옥스갈(oxgall) 3%(v/v)에서 100% 생존율을 보여 강한 내담즙성을 가진다.The Lactobacillus plantarum DSR M2 (Accession No .: KFCC-11432P) of the present invention isolated from kimchi survived at least 85% at pH 2.5 and was found to have strong acid resistance and to exhibit 90% or more of NaCl 15% (v / v) Has a strong salt tolerance and survival rate of 100% at oxgall 3% (v / v).
본 발명의 유효성분은 상기 식물성 락토바실러스 플란타륨 DSR M2의 생균, 건조균, 사균 또는 균체를 포함하거나 포함하지 않는 배양액이다.The active ingredient of the present invention is a culture solution containing or not containing live cells, dried germs, dead cells or cells of the plant Lactobacillus plantarum DSR M2.
본 발명에서 사균은 본 발명의 식물성 락토바실러스 플란타륨 DSR M2를 배양한 후 가열, 초음파, 효소, 압력, 산 및 염기 등의 처리를 통해 생균을 사멸시킨 사균으로서, 유산균의 발효에 의한 대사산물을 포함하는 배양액을 포함하거나 포함하지 않을 수 있다. 발효에 의한 배양액을 포함시키지 않을 경우 발효시킨 배양액을 여과 또는 원심분리하여 균체를 회수한 후 생균을 사멸시키거나, 먼저 사멸시킨 후 배양액으로부터 사멸된 균체를 회수할 수도 있다.In the present invention, dead cells are killed dead plants by culturing the plant Lactobacillus plantarum DSR M2 of the present invention and then treating them with heating, ultrasonic waves, enzymes, pressures, acids and bases, And the like. If the fermentation broth is not contained, the fermentation broth may be filtered or centrifuged to recover the bacterial cells and kill the viable cells, or may first kill the cells and recover the killed cells from the culture broth.
본 발명에서 락토바실러스 플란타륨 DSR M2를 배양하는 경우, 배지의 조성이나 배양 조건은 당업계에 알려진 적당한 배지와 배양조건에 따라 이루어질 수 있다. 이러한 배양과정은 당업자라면 선택되는 균주에 따라 용이하게 조정하여 사용할 수 있다. 이러한 다양한 배양 방법은 다양한 문헌(예를 들면, James et al., Biochemical Engineering, Prentice-Hall International Editions)에 개시되어 있다.In the present invention, when the lactobacillus plantarum DSR M2 is cultured, the composition of the culture medium and the culture conditions may be carried out according to a suitable culture medium and culture conditions known in the art. Such a culturing process can be easily adjusted according to the strain selected by those skilled in the art. These various methods of culturing are disclosed in various publications (e.g., James et al., Biochemical Engineering, Prentice-Hall International Editions).
예를 들어, 김치에서 유래된 본 발명의 식물성 락토바실러스 플란타륨 DSR M2는 식물성 배지 100 중량부에 각각의 균주 0.01 내지 3 중량부를 첨가하여 제조할 수 있다. 상기 식물성 배지는 식물성 배지 100 중량부에 10 내지 40 중량부의 배추 및 10 내지 40 중량부의 무를 포함할 수 있고, 바람직하게는 0.1 내지 5 중량부의 포도당 및/또는 0.1 내지 5 중량부의 효모 추출물을 더 포함할 수 있다. 상기 식물성 배지에 락토바실러스 플란타륨 DSR M2를 접종한 후 25 내지 40℃에서 2 내지 5일간 발효하여 균체를 포함하는 발효액을 얻을 수 있고, 균체가 제거된 발효액은 균체를 포함하는 발효액을 원심분리하여 상등액만 농축하여 얻을 수 있다.
For example, the plant Lactobacillus plantarum DSR M2 of the present invention derived from kimchi can be prepared by adding 0.01 to 3 parts by weight of each strain to 100 parts by weight of the plant medium. The vegetable medium may include 10 to 40 parts by weight of Chinese cabbage and 10 to 40 parts by weight of radish in 100 parts by weight of the vegetable medium, preferably 0.1 to 5 parts by weight of glucose and / or 0.1 to 5 parts by weight of yeast extract can do. Lactobacillus plantarum DSR M2 is inoculated to the plant medium and fermented at 25 to 40 DEG C for 2 to 5 days to obtain a fermentation broth containing the cells. The fermentation broth in which the cells are removed can be obtained by centrifuging the fermentation broth containing the cells So that only the supernatant can be obtained.
본 발명에서 인플루엔자 바이러스에 대한 항바이러스 활성을 가지는 유효성분은 상기 락토바실러스 플란타륨 DSR M2 유산균으로서, 안전성이 입증된 유산균으로부터 유래되어 부작용의 우려 없이 인플루엔자 바이러스 감염으로 인한 질환을 예방 또는 치료하기 위한 약학 조성물, 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 식품 조성물, 식품 첨가제 조성물, 생균제 조성물, 사료 조성물, 사료 첨가제 조성물, 발효식품 및 소독용 또는 세정용 조성물 등의 유효성분으로 이용될 수 있다. 상기 인플루엔자 바이러스는 H1N1 아형 및 H3N2 아형의 A형 인플루엔자 바이러스로 이루어진 군으로부터 선택되는 1종의 A형 인플루엔자 바이러스 또는 Victoria lineage 및Yamagata lineage로 이루어진 B형 인플루엔자 바이러스 군으로부터 선택되는 1종의 B형 인플루엔자 바이러스인 것이 바람직하다. 더욱 바람직한 것은 A/California/7/2009(H1N1)pdm09-like virus, A/Hong Kong/4801/2014(H3N2)-like virus, B/Brisbane/60/2008-like virus 및 B/Phuket/3073/2013-like virus 중에서 선택된 1종의 인플루엔자 바이러스이다.In the present invention, the active ingredient having antiviral activity against influenza virus is the Lactobacillus plantarum DSR M2 lactic acid bacterium, which is derived from a lactic acid bacterium which has been proven to be safe, and is used for preventing or treating diseases caused by influenza virus infection without fear of side effects A pharmaceutical composition, a food composition for preventing or improving an influenza virus infection disease, a food additive composition, a probiotics composition, a feed composition, a feed additive composition, a fermented food, and a composition for cleaning or disinfecting. Wherein said influenza virus is one type A influenza virus selected from the group consisting of H1N1 subtypes and H3N2 subtype A influenza viruses or one type B influenza virus selected from the group consisting of Victoria lineage and Yamagata lineage . (H1N1) pdm09-like virus, A / Hong Kong / 4801/2014 (H3N2) -like virus, B / Brisbane / 60 / 2013-like virus.
본 명세서에서, '치료'는 증상의 경감 또는 개선, 질환 범위의 감소, 질환 진행의 지연 또는 완화, 질환 상태의 개선, 경감 또는 안정화, 부분적 또는 완전한 회복, 생존의 연장 기타 다른 이로운 치료 결과 등을 모두 포함하는 의미로 사용된다.As used herein, " treatment " refers to the treatment or amelioration of symptoms, reduction of disease extent, delay or alleviation of disease progression, improvement, alleviation or stabilization of disease state, partial or complete recovery, It is used to mean both inclusive.
본 발명에 따른 상기 바이러스 감염으로 인한 질환으로는 예를 들면, 독감, 감기, 인후염, 기관지염, 폐렴, 조류독감, 돼지독감, 염소독감 등의 인플루엔자 바이러스 감염으로 인한 질환을 들 수 있으나, 이에 제한되는 것은 아니다.
Examples of the diseases caused by the viral infection according to the present invention include diseases caused by influenza virus infection such as influenza, cold, sore throat, bronchitis, pneumonia, avian influenza, swine flu and chlorine influenza, It is not.
더욱 구체적으로, 본 발명은 바람직한 구현예로서 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432P] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스에 대한 항바이러스용 약학 조성물을 제공한다.
More specifically, the present invention provides an antiviral pharmaceutical composition for influenza virus containing, as a preferred embodiment, Lactobacillus plantarum DSR M2 (Accession No .: KFCC-11432P) or a culture thereof as an active ingredient.
상기 약학 조성물은 바람직하게는 경구 제형으로 제제화될 수 있으며, 예를 들어 액제, 현탁제, 산제, 과립제, 정제, 캡슐제, 환제 또는 엑스제와 같은 경구 투여용 제형으로 제제화될 수 있다. 그리고, 각각의 제형으로 제제화할 때에는, 각각의 제형의 제조에 필요한 약제학적으로 허용 가능한 담체 또는 첨가제를 부가하여 제조할 수 있다. 대표적으로 경구 투여용 제형으로 제제화시 담체로서 희석제, 활택제, 결합제, 붕해제, 감미제, 안정제 및 방부제 중에서 1종 이상을 선택하여 사용할 수 있으며, 첨가제로는 향료, 비타민류 및 항산화제 중에서 1종 이상을 선택하여 사용할 수 있다.The pharmaceutical composition may be formulated into oral formulations, and may be formulated into oral dosage forms such as, for example, solutions, suspensions, powders, granules, tablets, capsules, pills or extensions. When formulating each formulation, a pharmaceutically acceptable carrier or additive necessary for the preparation of each formulation can be added. Typically, it is a form for oral administration. At the time of formulation, one or more of carriers such as a diluent, a lubricant, a binder, a disintegrant, a sweetener, a stabilizer and an antiseptic can be selected and used as an additive. Or more can be selected and used.
상기 담체 및 첨가제는 약제학적으로 허용 가능한 것은 모두 가능하며, 구체적으로 희석제로는 유당, 옥수수 전분, 대두유, 미정질 셀룰로오스, 또는 만니톨, 활택제로는 스테아린산 마그네슘 또는 탈크, 결합제로는 폴리비닐피롤리돈 또는 히드록시프로필셀룰로오스가 바람직하다. 또한, 붕해제로는 카르복시메틸셀룰로오스 칼슘, 전분글리콜산나트륨, 폴라크릴린칼륨, 또는 크로스포비돈, 감미제로는 백당, 과당, 솔비톨, 또는 아스파탐, 안정제로는 카르복시메틸셀룰로오스나트륨, 베타-사이클로덱스트린, 백납, 또는 잔탄검, 방부제로는 파라옥시안식향산메틸, 파라옥시안식향산프로필, 또는 솔빈산칼륨이 바람직하다.Examples of the diluent include lactose, corn starch, soybean oil, microcrystalline cellulose, or mannitol as the diluent, magnesium stearate or talc as the lubricant, polyvinylpyrrolidone as the binder, Or hydroxypropylcellulose are preferable. Examples of the disintegrant include carboxymethylcellulose calcium, sodium starch glycolate, polacrilin potassium, or crospovidone; examples of sweeteners include white sugar, fructose, sorbitol, or aspartame; stabilizers include sodium carboxymethylcellulose, Preferred examples of the antiseptic agent include methyl paraoxybenzoate, propyl paraoxybenzoate, and potassium sorbate.
또한, 상기 성분 이외에도 공지의 첨가제로서 미각을 돋구기 위하여, 매실향, 레몬향, 파인애플향, 허브향 등의 천연향료, 천연과즙, 클로로필린, 플라보노이드 등의 천연색소, 과당, 벌꿀, 당알코올, 설탕과 같은 감미성분, 또는 구연산, 구연산 나트륨과 같은 산미제를 혼합하여 사용할 수도 있다. 이러한 제제화 방법 및 제제화시 필요한 담체 및 첨가제에 대해서는 Remington's Pharmaceutical Sciences(19th ed., 1995)에 상세하게 기재되어 있다.In addition to the above components, natural additives such as natural flavors such as plum flavor, lemon flavor, pineapple flavor and herb flavor, natural fruit juice, natural coloring matters such as chlorophyllin and flavonoid, fructose, honey, sugar alcohol, sugar Or acidic agents such as citric acid and sodium citrate may be mixed and used. These formulations and the carriers and additives required for formulation are described in detail in Remington's Pharmaceutical Sciences (19 th ed., 1995).
본 발명의 약학 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서 본 발명의 락토바실러스 플란타륨 DSR M2를 1일 0.01mg/kg 내지 10g/kg으로, 바람직하게는 1mg/kg 내지 1g/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the drug form, the administration route and the period, but can be appropriately selected by those skilled in the art. However, it is preferable to administer the Lactobacillus plantarum DSR M2 of the present invention at a dose of 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg per day, for a preferable effect. The administration may be carried out once a day or divided into several times. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.
본 발명의 약학 조성물은 쥐, 생쥐, 가축, 인간 등의 포유 동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내(intracerebroventricular) 주사에 의해 투여될 수 있다.
The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.
또한 본 발명의 바람직한 또 다른 구현예들로서 상기의 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432P] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 식품 조성물 또는 식품 첨가제 조성물을 제공한다.In yet another preferred embodiment of the present invention, there is provided a food composition or food composition for preventing or ameliorating an influenza virus infectious disease comprising Lactobacillus plantarum DSR M2 [accession number: KFCC-11432P] or a culture thereof as an active ingredient An additive composition is provided.
상기 식품 조성물은 산제, 과립제, 캅셀제, 현탁액, 에멀젼, 시럽제, 액제, 엑스제와 같은 건강기능식품으로 제조될 수 있고, 치즈, 김치, 발효소시지, 발효생식제품과 같은 발효 식품으로 제조될 수 있으며, 음료, 이유식, 유제품, 차, 젤리 등의 일반 식품으로 제조될 수 있다. 또한 상기 식품 조성물의 제조에 필요한 식품 첨가제 조성물로도 이용될 수 있다.The food composition may be manufactured as a health functional food such as a powder, a granule, a capsule, a suspension, an emulsion, a syrup, a liquid, an extract, and may be manufactured as a fermented food such as cheese, kimchi, fermented sausage, , Beverages, baby foods, dairy products, tea, jellies, and the like. It may also be used as a food additive composition necessary for the production of the food composition.
본 발명의 락토바실러스 플란타륨 DSR M2가 식품 조성물 또는 식품 첨가제 조성물에 포함될 때 그 양은 건조물 또는 고형인 경우 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 음료인 경우 100㎖를 기준으로 0.02 내지 10g, 바람직하게는 0.3 내지 1g의 비율로 가할 수 있다.When the Lactobacillus plantarum DSR M2 of the present invention is contained in a food composition or a food additive composition, the amount thereof may be 0.01 to 15% by weight based on the total weight of the dried or solid food, and 0.02 To 10 g, preferably from 0.3 to 1 g.
식품 조성물 또는 식품 첨가제 조성물로서 이용될 경우 식품학적으로 허용 가능한 담체 또는 첨가제와 함께 당해 기술분야에 공지되어 있는 통상적인 제형으로 제제화될 수 있다. 상기 식품학적으로 허용 가능한 담체 또는 첨가제는 제조하고자 하는 제형의 제조에 당해 기술분야에서 사용 가능한 것으로 공지되어 있는 임의의 담체 또는 첨가제가 이용될 수 있다. When used as a food composition or food additive composition, may be formulated into conventional formulations known in the art, together with a pharmaceutically acceptable carrier or excipient. The pharmaceutically acceptable carrier or additive may be any carrier or additive known to be usable in the art for the preparation of the formulation to be prepared.
본 발명의 식품 조성물이 음료 형태로 제조되는 경우 지시된 비율로 필수 성분으로서 상기 본 발명의 락토바실러스 플란타륨 DSR M2를 함유하는 것 외에 액체성분에는 특별한 제한점은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등의 디사카라이드, 예를 들어 말토스, 슈크로스 등의 폴리사카라이드, 예를 들어, 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등)) 및 합성 향미제(사카린, 아스파탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 음료 100㎖ 당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g이다.When the food composition of the present invention is prepared in a beverage form, there are no particular limitations on the liquid ingredient other than the above-mentioned lactobacillus plantarum DSR M2 of the present invention as an essential ingredient in the indicated ratios, and various flavors Or natural carbohydrate as an additional ingredient. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose, polysaccharides such as maltose, sucrose, and the like, such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol, and erythritol. Natural flavors (tautatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the beverage of the present invention.
또한, 본 발명의 식품 조성물 또는 식품 첨가제 조성물은 유효성분으로 사용되는 본 발명의 락토바실러스 플란타륨 DSR M2 이외에 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 증진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 식품 조성물 또는 식품 첨가제 조성물은 본 발명의 락토바실러스 플란타륨 DSR M2 이외에 천연 과일 주스 및 과일 주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.
In addition, the food composition or food additive composition of the present invention may contain, in addition to the Lactobacillus plantarum DSR M2 of the present invention, which is used as an active ingredient, a flavor such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors , Colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, ≪ / RTI > In addition, the food composition or food additive composition of the present invention may contain, in addition to the Lactobacillus plantarum DSR M2 of the present invention, natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
또한 본 발명의 바람직한 또 다른 구현예들로서 상기의 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432P] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스 감염 질환의 예방 또는 개선용 사료 조성물 또는 사료 첨가제 조성물을 제공한다.In yet another preferred embodiment of the present invention, there is provided a feed composition or feed composition for preventing or ameliorating an influenza virus infectious disease comprising the above-mentioned Lactobacillus plantarum DSR M2 [Accession No .: KFCC-11432P] or a culture thereof as an active ingredient An additive composition is provided.
락토바실러스 플란타륨 DSR M2가 사료 조성물 또는 사료 첨가제 조성물에 함유되어 이용될 경우, 상기 조성물은 20 내지 90% 고농축액이거나 분말 또는 과립형태로 제조될 수 있다. 상기 사료 첨가제는 구연산, 후말산, 아디픽산, 젖산, 사과산 등의 유기산이나 인산나트륨, 인산칼륨, 산성 피로인산염, 폴리인산염(중합인산염) 등의 인산염이나, 폴리페놀, 카테킨, 알파-토코페롤, 로즈마리 추출물, 비타민 C, 녹차 추출물, 감초 추출물, 키토산, 탄닌산, 피틴산 등의 천연 항산화제 중 어느 하나 또는 하나 이상을 추가로 포함할 수 있다. 사료로 이용될 경우, 상기 조성물은 통상의 사료 형태로 제제화될 수 있으며, 통상의 사료 성분을 함께 포함할 수 있다. 상기 사료 첨가제 및 사료는 곡물, 예를 들면 분쇄 또는 파쇄된 밀, 귀리, 보리, 옥수수 및 쌀; 식물성 단백질 사료, 예를 들면 평지, 콩 및 해바라기를 주성분으로 하는 사료; 동물성 단백질 사료, 예를 들면 혈분, 육분, 골분 및 생선분; 당분 및 유제품, 예를 들면 각종 분유 및 유장 분말로 이루어지는 건조 성분 등을 더 포함할 수 있으며, 이외에도 영양 보충제, 소화 및 흡수 향상제, 성장 촉진제 등을 더 포함할 수 있다. 상기 사료 첨가제는 동물에게 단독으로 투여하거나 식용 담체 중에서 다른 사료 첨가제와 조합하여 투여할 수도 있다. 또한, 상기 사료 첨가제는 탑 드레싱으로서 또는 이들을 동물 사료에 직접 혼합하거나 또는 사료와 별도의 경구 제형으로 용이하게 동물에게 투여할 수 있다. 상기 사료 첨가제를 동물 사료와 별도로 투여할 경우, 당해 기술분야에 잘 알려진 바와 같이 약제학적으로 허용 가능한 식용 담체와 조합하여, 즉시 방출 또는 서방성 제형으로 제조할 수 있다. 이러한 식용 담체는 고체 또는 액체, 예를 들어 옥수수 전분, 락토오스, 수크로오스, 콩 플레이크, 땅콩유, 올리브유, 참깨유 및 프로필렌글리콜일 수 있다. 고체 담체가 사용될 경우, 사료 첨가제는 정제, 캡슐제, 산제, 트로키제 또는 함당정제 또는 미분산성 형태의 탑 드레싱일 수 있다. 액체 담체가 사용될 경우, 사료 첨가제는 젤라틴 연질 캡슐제, 또는 시럽제나 현탁액, 에멀젼제, 또는 용액제의 제형일 수 있다. 상기 사료는 동물의 식이 욕구를 충족시키는데 통상적으로 사용되는 임의의 단백질-함유 유기 곡분을 포함할 수 있다. 이러한 단백질-함유 곡분은 통상적으로 옥수수, 콩 곡분, 또는 옥수수/콩 곡분 믹스로 구성되어 있다. 또한 사료 조성물 또는 사료 첨가제 조성물은 예를 들어 보존제, 안정화제, 습윤제 또는 유화제, 용액 촉진제 등을 함유할 수 있다. 또한 사료 첨가제 조성물은 침주, 분무 또는 혼합하여 동물의 사료에 첨가하여 이용될 수 있다.
When Lactobacillus plantarum DSR M2 is used in a feed or feed additive composition, the composition may be 20 to 90% high concentrate or may be prepared in powder or granular form. The feed additive may be selected from the group consisting of organic acids such as citric acid, fumaric acid, adipic acid, lactic acid and malic acid, phosphates such as sodium phosphate, potassium phosphate, acid pyrophosphate, polyphosphate (polymerized phosphate), polyphenol, catechin, alpha-tocopherol, Extract, vitamin C, green tea extract, licorice extract, chitosan, tannic acid, phytic acid, and the like. When used as a feed, the composition may be formulated in conventional feed form and may contain conventional feed ingredients. The feed additives and feeds may be selected from the group consisting of cereals, such as ground or crushed wheat, oats, barley, corn and rice; Vegetable protein feeds such as feeds based on rapeseed, beans and sunflower; Animal protein feeds such as blood, meat, bone meal and fish meal; A sugar or a milk product, for example, a dry component comprising various powdered milk and whey powder, and may further include nutritional supplements, digestion and absorption enhancers, growth promoters, and the like. The feed additive may be administered to animals singly or in combination with other feed additives in edible carriers. The feed additives can also be administered to the animal either as a top dressing or they can be mixed directly with the animal feed or in a separate oral form separate from the feed. When the feed additive is administered separately from an animal feed, it can be prepared in an immediate release or sustained release formulation, in combination with a pharmaceutically acceptable edible carrier as is well known in the art. Such edible carriers may be solid or liquid, such as corn starch, lactose, sucrose, soy flakes, peanut oil, olive oil, sesame oil and propylene glycol. When a solid carrier is used, the feed additive can be a tablet, capsule, powder, troche or emulsion or top-dressing in finely divided form. When a liquid carrier is used, the feed additive can be a gelatin soft capsule, or a syrup or suspension, emulsion, or solution formulation. The feed may comprise any protein-containing organic fructose commonly used to meet an animal's dietary needs. These protein-containing flours usually consist of corn, soy flour, or corn / soy flour mix. The feed composition or feed additive composition may also contain, for example, preservatives, stabilizers, wetting or emulsifying agents, solution promoters, and the like. The feed additive composition may also be used by adding to the feed of the animal by soaking, spraying or mixing.
또한 본 발명의 바람직한 또 다른 구현예들로서, 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432P] 또는 이의 배양물을 유효성분으로 함유하는 인플루엔자 바이러스 소독용 또는 세정용 조성물을 제공한다. 상기 조성물은 소독제, 주방세제, 세탁세제, 야채·채소 세척제 또는 손 세정제에 사용될 수 있으나, 이에 한정되는 것은 아니다.In yet another preferred embodiment of the present invention, there is provided a composition for disinfection or cleaning of influenza virus containing Lactobacillus plantarum DSR M2 (Accession No. KFCC-11432P) or a culture thereof as an active ingredient. The composition may be used in disinfectants, kitchen detergents, laundry detergents, vegetable or vegetable detergents, or hand cleaners, but is not limited thereto.
본 발명의 소독용 또는 세정용 조성물은 하나 이상의 계면활성제를 포함할 수 있다. 상기 계면활성제는 음이온성, 비-이온성, 양이온성, 양쪽성 또는 양이온성 형태(zwitter ionic type), 또는 이것들의 혼합물일 수 있다. 음이온성 계면활성제의 대표적인 예로는 선형 알킬벤젠술폰산염(LAS), 알킬황산염(AS), 알파올레핀술폰산염(AOS), 알코올에톡시황산염(AES) 또는 천연지방산의 알칼리금속염을 들 수 있다. 비-이온성 계면활성제의 예로는 알킬폴리에틸렌글리콜에테르, 노닐페놀 폴리에틸렌글리콜 에테르, 수크로스와 글루코스의 지방산에스테르 또는 폴리에톡실화 알킬글루코시드의 에스테르를 들 수 있다.The disinfecting or cleaning compositions of the present invention may comprise one or more surfactants. The surfactant may be anionic, non-ionic, cationic, amphoteric or zwitterionic type, or a mixture thereof. Representative examples of anionic surfactants include linear alkylbenzenesulfonic acid salts (LAS), alkylsulfuric acid salts (AS), alpha olefin sulfonic acid salts (AOS), alcohol ethoxy sulfate (AES) or alkali metal salts of natural fatty acids. Examples of non-ionic surfactants include alkylpolyethylene glycol ethers, nonylphenol polyethylene glycol ethers, fatty acid esters of sucrose with glucose or esters of polyethoxylated alkyl glucosides.
또한, 본 발명의 소독용 또는 세정용 조성물은 용도에 맞추어 연마제, 표백제, 표면활성제, 부식방지제, 금속봉쇄제, 얼룩-재침착 방지제, 향수, 효소 및 표백제의 안정화제, 제형 보조제, 광증백제, 거품 부스터, 킬레이트화제, 충전제, 직물연화제 등과 같은 당업계에서 공지된 다른 세제 성분들을 추가로 포함할 수 있다. 또한, 본 발명의 소독용 또는 세정용 조성물은 분제, 액제 등의 임의의 편리한 형태로 제형화될 수 있다.
The composition for disinfecting or cleaning according to the present invention can be suitably used for various purposes such as an abrasive, a bleaching agent, a surface active agent, a corrosion inhibitor, a metal blocker, a stain-repellent agent, a perfume, a stabilizer for enzymes and bleaching agents, Foam boosters, chelating agents, fillers, fabric softeners, and the like, as well as other detergent ingredients known in the art. In addition, the disinfecting or cleaning composition of the present invention may be formulated into any convenient form such as powder or liquid.
이하, 본 발명의 구성을 실시예를 통하여 보다 상세히 설명한다. 단, 하기 실시예 및 실험예는 본 발명의 내용을 예시하는 것일 뿐 발명의 범위가 이에 한정되는 것은 아니고, 본 발명의 기술 사상 범위 내에서 여러 가지로 변형하여 실시하는 것이 가능하며, 이 또한 첨부된 특허 청구 범위에 속하는 것은 당연하다.
Hereinafter, the structure of the present invention will be described in more detail with reference to examples. It is to be understood, however, that the invention is not limited to the disclosed embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. It is obvious that the present invention belongs to the claims.
[[ 실시예Example ]]
제조예Manufacturing example 1: One: 락토바실러스Lactobacillus 플란타륨Pantalum DSRDSR M2의 배양 Culture of M2
김치에서 분리한 락토바실러스 플란타륨 DSR M2를 배양하기 위해, MRS 배지[MRS, 디프코(Difco.); 박토 펩톤 10g, 소고기 추출물 10g, 효모추출물 5g, 글루코스 20g, 트윈80 1g, 구연산 2g, 제2 인산칼륨 2g, 초산나트륨 5g, 황산망간 0.1g, 황산마그네슘 0.05g, 증류수 1ℓ]에 락토바실러스 플란타륨 DSR M2[기탁번호: KFCC-11432P]를 접종한 후, 37℃에서 24시간 배양하였다. 이후, 3차 계대 배양된 락토바실러스 플란타륨 DSR M2균을 원심분리하고 균체를 10% 탈지유에 현탁하여 -70℃에서 보관하였다.To culture Lactobacillus plantarum DSR M2 isolated from kimchi, MRS medium [MRS, Difco .; 10 g of bovine peptone, 10 g of beef extract, 5 g of yeast extract, 20 g of glucose, 80 g of tween 80, 2 g of citric acid, 2 g of potassium diphosphate, 5 g of sodium acetate, 0.1 g of manganese sulfate, 0.05 g of magnesium sulfate, (DSM M2 [accession number: KFCC-11432P]), followed by incubation at 37 ° C for 24 hours. Subsequently, the Lactobacillus plantarum DSR M2 strain cultured in the third passage was centrifuged, and the cells were suspended in 10% skim milk and stored at -70 ° C.
그리고, 상기 유산균을 MRS 액체 배지에 접종하여 37℃에서 24시간 배양하였다. 상기 균체를 포함하는 배양액을 4,000rpm, 4℃에서 10분간 원심분리하여 균체를 얻은 후 멸균된 PBS 완충용액을 이용하여 3회 세척하였다. 상기 세척한 균체를 다시 멸균된 PBS 완충용액에 현탁한 후 95℃에서 10분간 열처리하였다. 상기 열처리된 균을 4,000rpm, 4℃에서 10분간 원심분리하여 균체를 얻은 후 멸균된 PBS 완충용액 1㎖에 현탁하였다. 이 균 현탁액을 -20℃에 보관하면서 실험에 사용하였다.
Then, the lactic acid bacteria were inoculated into the MRS liquid medium and cultured at 37 占 폚 for 24 hours. The culture broth containing the cells was centrifuged at 4,000 rpm for 10 minutes at 4 ° C to obtain cells, which were then washed three times with sterilized PBS buffer solution. The washed cells were suspended in sterilized PBS buffer solution and heat-treated at 95 ° C for 10 minutes. The heat-treated bacterium was centrifuged at 4,000 rpm at 4 DEG C for 10 minutes to obtain cells, which were then suspended in 1 mL of sterilized PBS buffer solution. The suspension of this bacterium was used for the experiment while being stored at -20 ° C.
[[ 시험예Test Example ]]
시험예Test Example 1: One: 락토바실러스Lactobacillus 플란타륨Pantalum DSRDSR M2 유산균의 인플루엔자 바이러스에 대한 항바이러스 활성 실험 Experiment of antiviral activity against Influenza virus of Lactobacillus acidus M2
독감의 원인체인 인플루엔자 바이러스에 대한 항바이러스 활성을 분석하기 위하여 제조예 1의 락토바실러스 플란타륨 DSR M2를 불활화(heat-inactivation)하여 사용하였다. In order to analyze the antiviral activity against influenza virus causing the flu, Lactobacillus plantarum DSR M2 of Production Example 1 was heat-inactivated and used.
MDCK(Madin-Darby Canine Kidney) 세포는 미국 ATCC에서 구입하였으며, 10% 우태아혈청(fetal bovine serum, FBS)이 포함된 MEM(minimal essential medium)에서 배양하였으며, 배양기의 온도는 37℃, 이산화탄소 농도는 5%로 유지하였다.MDCK (Madin-Darby Canine Kidney) cells were purchased from ATCC USA and cultured in MEM (minimal essential medium) containing 10% fetal bovine serum (FBS). The temperature of the incubator was 37 ° C, Was maintained at 5%.
인플루엔자 바이러스는 국립보건원 질병관리본부에서 분양받은 A/Korea/01/2009(H1N1)를 사용하였다.Influenza viruses were used from A / Korea / 01/2009 (H1N1), which was distributed by the National Institute of Health's Disease Control Headquarters.
H1N1 아형의 A형 인플루엔자 바이러스(A/Korea/01/2009)를 감염시킨 MDCK(Madin-Darby Canine Kidney) 세포주에 상기 불활화시킨 제조예 1의 락토바실러스 플란타륨 DSR M2 유산균을 농도별(10%, 5%, 2.5%, 1.25%, 0.625%, 그리고 0%)로 넣은 overlay-agar media(2% Oxoid agarose sol(in DMEM-F12))를 덮은 뒤, 5% CO2, 37 배양기에서 72시간 배양한 후, 0.1%(v/v) 크리스탈 바이올렛으로 염색하여 플라크 형성 시험(Plaque Assay)을 실시하였다.
(MDCK) (Madin-Darby Canine Kidney) cell line infected with the H1N1 subtype of influenza A virus (A / Korea / 01/2009) was inoculated with the inactivated Lactobacillus plantarum DSR M2 lactic acid bacteria of Preparation Example 1 Agar media (2% Oxoid agarose sol (in DMEM-F12)) in 5% CO 2 and 37% incubator for 72 h in the presence of 5%, 5%, 2.5%, 1.25%, 0.625% After incubation for a time, the cells were stained with 0.1% (v / v) crystal violet to perform plaque assays.
항바이러스 활성의 결과는 인플루엔자 바이러스가 MDCK 세포주에서 형성하는 플라크(plaque) 형성 능력의 감소(직경의 감소)로 확인하였으며, 그 결과를 도 1에 나타냈었다. 상기 도 1에서 락토바실러스 플란타륨 DSR M2 유산균은 균주명의 마지막 알파벳을 이용하여 M2로 나타내었다.
The results of the antiviral activity were confirmed by a decrease in the ability of the influenza virus to form plaques formed in the MDCK cell line (decrease in diameter), and the results are shown in Fig. 1, the Lactobacillus plantarum DSR M2 lactic acid bacterium is represented by M2 using the last letter of the strain name.
상기 도 1에서 확인할 수 있는 바와 같이, 본 발명의 락토바실러스 플란타륨 DSR M2 유산균은 인플루엔자 바이러스의 플라크 형성을 상당히 효과적으로 억제하였다. 유산균 농도의 감소에 따라 플라크 형성 억제능이 감소하는 것(dose-dependent)으로 보아, 10%와 5%에서 확인된 플라크 직경의 감소는 유산균의 항바이러스 효능에서 기인한 것임이 증명된다.
As can be seen from FIG. 1, the Lactobacillus plantarum DSR M2 lactic acid bacteria of the present invention significantly inhibited plaque formation of influenza virus. It has been demonstrated that the decrease in plaque diameter observed at 10% and 5%, due to dose-dependent inhibition of plaque formation as the concentration of lactic acid bacteria decreases, is due to the antiviral efficacy of lactic acid bacteria.
하기에 본 발명의 조성물을 위한 제제예 또는 제조예를 예시한다.Formulation examples or preparation examples for the composition of the present invention are illustrated below.
<< 제제예Formulation example > 약학적 제제의 제조> Preparation of pharmaceutical preparations
1-1: 정제의 제조1-1: Preparation of tablets
제조예 1의 락토바실러스 플란타륨 DSR M2를 동결건조시킨 분말 100mg, 옥수수전분 100mg, 유당 100mg 및 폴리비닐피롤리돈 97mg을 균질하게 혼합하여 습식과립법으로 과립화하고 스테아린산 마그네슘 2mg을 가하여 혼합한 후 1정이 400mg이 되도록 타정하였다.
100 mg of the lyophilized powder of Lactobacillus plantarum DSR M2 of Production Example 1, 100 mg of corn starch, 100 mg of lactose and 97 mg of polyvinylpyrrolidone were homogeneously mixed and granulated by a wet granulation method, followed by mixing with 2 mg of magnesium stearate And one tablet was 400mg.
1-2: 캡슐제의 제조1-2: Preparation of capsules
제조예 1의 락토바실러스 플란타륨 DSR M2를 동결건조시킨 분말 100mg, 옥수수전분 100mg, 유당 100mg, 스테아린산 마그네슘 2mg을 완전히 혼합한 후 통상의 캡슐제의 제조방법에 따라서 경질 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.
100 mg of the lyophilized powder of the lactobacillus plantarum DSR M2 of Production Example 1, 100 mg of the corn starch, 100 mg of the lactose and 2 mg of the magnesium stearate were thoroughly mixed and filled in hard gelatin capsules according to a conventional preparation method of the capsules, .
<< 제조예Manufacturing example 2> 음료의 제조 2> Manufacturing of beverages
먼저, 혼합 과즙시럽은 액상과당 13중량%, 백설탕 2.5중량%, 갈색설탕 2.5중량%, 혼합과즙농축액 56Brix 10.9중량%, 펙틴 1.0중량%, 후레쉬 후르츠 믹스 에센스 0.1중량% 및 정제수 70중량%를 30~35℃에서 교반하여 혼합한 후 UHT 열처리(135℃에서 2초간 살균)한 후 냉각하여 제조하였다. 그리고 상기의 방법으로 제조된 혼합과즙시럽 30.4중량%와 상기 제조예 1의 락토바실러스 플란타륨 DSR M2를 동결건조시킨 분말 0.1중량% 및 나머지 정제수 69.5중량%를 조합하여 150bar에서 균질한 후 10℃ 이하로 냉각한 후 이를 유리병, 패트병 등 소포장 용기에 포장하여 음료를 제조하였다.
First, the mixed fruit juice syrup was prepared by mixing 30 wt% of liquid sugar, 13 wt% of fructose, 2.5 wt% of white sugar, 2.5 wt% of brown sugar, 10.9 wt% of concentrated juice concentrate, 1.0 wt% of pectin, 0.1 wt% of fresh fruit mix essence, The mixture was stirred at ~ 35 ° C, heat-treated by UHT (sterilized at 135 ° C for 2 seconds), and cooled. Then, 30.4% by weight of the mixed fruit juice syrup prepared by the above method and 0.1% by weight of the lyophilized powder of the lactobacillus plantarum DSR M2 of Preparation Example 1 and 69.5% by weight of the remaining purified water were combined and homogenized at 150 bar, And then packaged in a small container such as a glass bottle or a plastic bottle to prepare a beverage.
<< 제조예Manufacturing example 3> 발효소시지의 제조 3> Preparation of fermented sausage
제조예 1의 락토바실러스 플란타륨 DSR M2 동결건조시킨 분말 2중량%를 원료육 90중량%, 후추 0.25중량%, 마늘 0.05중량%, 로즈메리 0.05중량%, 식염 2.8중량%, 포도당 1중량% 및 정제수 잔량을 포함하는 소시지원료에 첨가한 후 15 내지 30℃에서 3개월간 발효하여 발효소시지를 제조하였다.
2% by weight of a powder obtained by lyophilization of Lactobacillus plantarum DSR M2 in Production Example 1 was added to a mixture of 90% by weight of raw material, 0.25% by weight of pepper, 0.05% by weight of garlic, 0.05% by weight of rosemary, 2.8% And added to the sausage raw material containing the remaining amount of purified water, followed by fermentation at 15 to 30 DEG C for 3 months to produce fermented sausage.
<< 제조예Manufacturing example 4> 건강기능식품( 4> Health Functional Foods ( 경질캡슐제Hard capsule )의 제조)
제조예 1의 락토바실러스 플란타륨 DSR M2를 동결건조시킨 분말 100mg100 mg of the lyophilized powder of Lactobacillus plantarum DSR M2 of Production Example 1
비타민 혼합물 적량Vitamin mixture quantity
비타민 A 아세테이트 70㎍70 비 of vitamin A acetate
비타민 E 1.0mgVitamin E 1.0mg
비타민 B1 0.13mg0.13 mg of vitamin B 1
비타민 B2 0.15mg0.15 mg of vitamin B 2
비타민 B6 0.5mgVitamin B 6 0.5 mg
비타민 B12 0.2㎍0.2 g of vitamin B 12
비타민 C 10mgVitamin C 10mg
비오틴 10㎍10 μg of biotin
니코틴산아미드 1.7mgNicotinic acid amide 1.7 mg
엽산 50㎍50 엽 of folic acid
판토텐산 칼슘 0.5mgCalcium pantothenate 0.5mg
무기질 혼합물 적량Mineral mixture quantity
황산제1철 1.75mg1.75 mg ferrous sulfate
산화아연 0.82mg0.82 mg of zinc oxide
탄산마그네슘 25.3mgMagnesium carbonate 25.3 mg
제1인산칼륨 15mg15 mg of potassium phosphate monobasic
제2인산칼슘 55mgCalcium phosphate diphosphate 55 mg
구연산칼륨 90mgPotassium citrate 90mg
탄산칼슘 100mgCalcium carbonate 100 mg
염화마그네슘 24.8mg
24.8 mg of magnesium chloride
상기 조성의 물질들을 고속회전 혼합기에서 혼합하였다. 상기 혼합물 100중량부에 멸균 정제수 10 중량부를 첨가, 혼합하고 직경 1~2mm의 과립상으로 성형하였다. 상기 성형된 과립을 40~50℃의 진공건조기에서 건조시킨 후 12~14메쉬를 통과시켜 균일한 크기의 과립으로 제조하였다. 상기와 같이 제조된 과립을 적당량씩 압출성형하고 경질캡슐에 충전시켜 경질캡슐제품으로 제조하였다.The materials of the above composition were mixed in a high-speed spin mixer. 10 parts by weight of sterilized purified water was added to 100 parts by weight of the mixture, and the mixture was granulated into granules having a diameter of 1 to 2 mm. The molded granules were dried in a vacuum drier at 40 to 50 DEG C and then passed through 12 to 14 mesh to prepare uniform granules. The granules thus prepared were extruded in suitable amounts and filled into hard capsules to prepare hard capsule products.
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강기능성 식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능성 식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고 이를 통상의 방법에 따라 건강기능성 식품 제조에 사용할 수 있다.
Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a component suitable for a health functional food as a preferred embodiment, the compounding ratio may be arbitrarily changed, and the above components may be mixed The granules can then be prepared and used in the manufacture of health functional foods according to conventional methods.
<< 제조예Manufacturing example 5> 사료의 제조 5> Production of feed
제조예 1의 락토바실러스 플란타륨 DSR M2 3중량%와 탈지강 97중량%를 단순 혼합한 후 40℃ 이하에서 건조시켰으며, 건조된 혼합물을 분쇄하여 사료를 제조하였다.
3% by weight of Lactobacillus plantarum DSR M2 of Preparation Example 1 and 97% by weight of degreasing agent were simply mixed and dried at 40 ° C or lower, and the dried mixture was pulverized to prepare a feed.
Claims (12)
Lactobacillus plantarum DSR M2 (accession number: KFCC-11432P) or its culture which is resistant to acid at pH 2.5, salt tolerance at 15% (v / v) NaCl and 3% (v / v) A / Korea / 01/2009 (H1N1) A pharmaceutical composition for antiviral against influenza A virus comprising as an active ingredient.
2. The antiviral pharmaceutical composition according to claim 1, wherein the composition is for preventing or treating a disease caused by an influenza virus infection.
4. The antiviral pharmaceutical composition according to claim 3, wherein the disease caused by the virus infection is one of influenza, cold, sore throat, bronchitis, pneumonia, avian influenza, swine flu and chlorophyll.
Lactobacillus plantarum DSR M2 (accession number: KFCC-11432P) or its culture which is resistant to acid at pH 2.5, salt tolerance at 15% (v / v) NaCl and 3% (v / v) A / Korea / 01/2009 (H1N1) which contains as an active ingredient an effective component for preventing or ameliorating influenza A virus infection.
Lactobacillus plantarum DSR M2 (accession number: KFCC-11432P) or its culture which is resistant to acid at pH 2.5, salt tolerance at 15% (v / v) NaCl and 3% (v / v) A / Korea / 01/2009 (H1N1) A food additive composition for preventing or ameliorating an influenza A virus infection disease comprising as an active ingredient.
Lactobacillus plantarum DSR M2 (accession number: KFCC-11432P) or its culture which is resistant to acid at pH 2.5, salt tolerance at 15% (v / v) NaCl and 3% (v / v) A / Korea / 01/2009 (H1N1), which contains Aspergillus oryzae as an active ingredient.
Lactobacillus plantarum DSR M2 (accession number: KFCC-11432P) or its culture which is resistant to acid at pH 2.5, salt tolerance at 15% (v / v) NaCl and 3% (v / v) (H1N1), which contains Aspergillus oryzae as an active ingredient, for the prevention or amelioration of an influenza A virus infection of type A / Korea / 01/2009 (H1N1).
Lactobacillus plantarum DSR M2 (accession number: KFCC-11432P) or its culture which is resistant to acid at pH 2.5, salt tolerance at 15% (v / v) NaCl and 3% (v / v) A / Korea / 01/2009 (H1N1) A feed additive composition for preventing or ameliorating an influenza A virus infection disease comprising as an active ingredient.
Lactobacillus plantarum DSR M2 (accession number: KFCC-11432P) or its culture which is resistant to acid at pH 2.5, salt tolerance at 15% (v / v) NaCl and 3% (v / v) A / Korea / 01/2009 (H1N1) A fermented food for preventing or ameliorating influenza A virus infectious disease comprising as an active ingredient.
Lactobacillus plantarum DSR M2 (accession number: KFCC-11432P) or its culture which is resistant to acid at pH 2.5, salt tolerance at 15% (v / v) NaCl and 3% (v / v) A / Korea / 01/2009 (H1N1) for the disinfection or cleaning of type A influenza virus.
12. The composition of claim 11, wherein the composition is used in a disinfectant, a kitchen detergent, a laundry detergent, a vegetable or vegetable detergent, or a hand cleaner.
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KR102007421B1 (en) * | 2019-01-18 | 2019-08-05 | 한국생명공학연구원 | Composition for anti-influenza virus comprising as active ingredient polysaccharide derived from Lactobacillus plantarum and method for producing the polysaccharide |
KR102439760B1 (en) | 2021-03-09 | 2022-09-02 | 주식회사 오라팜 | Composition for the prevention and/or treatment of upper respiratory virus infections |
KR102451861B1 (en) | 2021-03-09 | 2022-10-07 | 주식회사 오라팜 | Composition for the prevention and/or treatment of acute respiratory viruses and rotavirus infections |
KR20230045675A (en) * | 2021-09-27 | 2023-04-05 | 주식회사 프로바이오닉 | Novel Lactobacillus plantarum Probio-88, extract amd composition thereof |
CN113785986A (en) * | 2021-10-13 | 2021-12-14 | 河北一然生物科技股份有限公司 | New application of lactobacillus plantarum LP45 in resisting influenza virus |
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KR101287120B1 (en) * | 2011-10-28 | 2013-07-17 | 대상에프앤에프 주식회사 | Composition comprising Lactobacillus plantarum DSR CK10 or Lactobacillus plantarum DSR M2 as an effective ingredient for treatment of cancer |
KR20150044764A (en) * | 2013-10-17 | 2015-04-27 | 주식회사 토비코 | A novel Lactobacillus plantarum and use of the same |
KR101666564B1 (en) * | 2014-10-22 | 2016-10-17 | 주식회사 프로바이오닉 | Lactobacillus plantarum Probio 090 having anti-virus and anti-pathogenic bacterial activity and products from Lactobacillus plantarum Probio 090 |
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KR20210089352A (en) * | 2020-01-08 | 2021-07-16 | 건국대학교 산학협력단 | Anti-influenza viral composition comprising fermentated extract of inula britannica flower |
KR102416208B1 (en) | 2020-01-08 | 2022-07-01 | 건국대학교 산학협력단 | Anti-influenza viral composition comprising fermentated extract of inula britannica flower |
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