KR20230118790A - Composition for preventing or treating sepsis and pain comprising extracts of Dracocephalum moldavica - Google Patents
Composition for preventing or treating sepsis and pain comprising extracts of Dracocephalum moldavica Download PDFInfo
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
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Abstract
본 발명은 향청란(Dracocephalum moldavica) 추출물을 유효성분으로 포함하는 패혈증 예방, 개선 또는 치료용 조성물에 관한 것으로, 본 발명의 상기 향청란 추출물을 포함하는 조성물은 마우스 모델에서 패혈증으로 인해 증가된 염증성 사이토카인을 감소시키는 것을 특징으로 한다. 구체적으로는, iNOS, COX2, 및 IL-6의 mRNA 및 단백질의 발현을 감소시켜 패혈증 또는 통증을 예방, 개선, 또는 치료하는 것을 특징으로 하며, 이에 따라 상기 조성물이 패혈증에 의한 사망율을 감소시켜 생존율을 개선시키고, 염증성 통증 및 신경병증성 통증 반응을 감소시키는 효과를 나타냄을 확인하여, 상기 조성물은 패혈증 또는 통증의 예방, 치료 또는 개선용 조성물로 유용하게 사용될 수 있다.The present invention relates to a composition for preventing, ameliorating or treating sepsis comprising an extract of Dracocephalum moldavica as an active ingredient, and the composition containing the extract of the scented orchid of the present invention suppresses increased inflammatory cytokines due to sepsis in a mouse model. characterized by reducing Specifically, it is characterized by preventing, improving, or treating sepsis or pain by reducing the expression of mRNA and protein of iNOS, COX2, and IL-6, and accordingly, the composition reduces the mortality rate due to sepsis and increases the survival rate. By confirming that the composition exhibits an effect of improving and reducing inflammatory pain and neuropathic pain response, the composition can be usefully used as a composition for preventing, treating, or improving sepsis or pain.
Description
본 발명은 향청란(Dracocephalum moldavica) 추출물을 유효성분으로 포함하는 패혈증 또는 통증의 예방, 개선 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing, improving or treating sepsis or pain, comprising an extract of Dracocephalum moldavica as an active ingredient.
패혈증(Sepsis)은 감염에 대한 비정상적인 숙주 반응으로 인해 발병되는 질환이다. 세계적으로 30일 이내 사망률이 20~30%에 달하고 국내 패혈증에 의한 사망률 역시 약 34.3%로 뇌졸중(9.3%), 심근경색(9.6%)보다 훨씬 높은 사망률을 기록하고 있지만 패혈증에 대한 인지도는 매우 낮은 실정이다. 최근 인구의 노령화와 만성질환자의 수명이 연장되고, 에이즈 등으로 면역력이 저하된 환자가 늘어나면서 감염으로 인한 패혈증 발생과 사망하는 환자 수가 급격히 증가하고 있다.Sepsis is a disease caused by an abnormal host response to infection. Globally, the mortality rate within 30 days reaches 20-30%, and the mortality rate due to sepsis in Korea is also about 34.3%, which is much higher than that of stroke (9.3%) and myocardial infarction (9.6%). The situation is. Recently, as the population ages, the lifespan of chronic diseases is extended, and the number of patients with reduced immunity due to AIDS increases, the number of septicemia and death due to infection is rapidly increasing.
현재 사용되고 있는 패혈증의 치료제로는 항생제와 스테로이드제 투여, 그리고 혈역학적인 보조제가 복합적으로 사용되고 있으나, 임상적으로 사망률에 뚜렷한 효과를 보이는 치료제 개발은 여전히 미흡한 실정이다. 패혈증의 진행과정에서 나타나는 임상적 특성의 하나가 전신에 걸친 체내 염증계가 과활성화되는 것이므로, 패혈증의 치료를 위하여 이러한 염증반응을 수반하거나 촉진하는 TNF-α, 인터루킨-1(IL-1), 인터루킨-6(IL-6) 및 HMGB1 등의 염증 유발 매개체를 억제할 수 있는 저해제 또는 억제제들을 중심으로 수많은 시도가 있어왔으나 환자의 생존율을 개선하지 못해 개발에 실패하였고, 현재까지 임상시험을 통과하여 패혈증 치료제로 개발에 성공한 사례가 거의 없다. 따라서, 패혈증을 예방 또는 치료하기 위해서는 염증 유발 사이토카인의 농도를 억제할 뿐만 아니라 패혈증으로 인한 사망율, 즉 생존율을 개선시키는 것이 매우 중요하다.Antibiotics, steroid administration, and hemodynamic adjuvant are currently being used as a treatment for sepsis, but the development of a treatment that shows a clear clinical effect on mortality is still insufficient. Since one of the clinical characteristics of the course of sepsis is overactivation of the body's inflammatory system throughout the body, TNF-α, interleukin-1 (IL-1), and interleukins that accompany or promote such an inflammatory response for the treatment of sepsis Numerous attempts have been made, centering on inhibitors or inhibitors that can inhibit inflammation-inducing mediators such as -6 (IL-6) and HMGB1, but failed to improve the patient's survival rate and failed to develop. There are few cases of successful development as a treatment. Therefore, in order to prevent or treat sepsis, it is very important not only to suppress the concentration of inflammatory cytokines but also to improve the mortality rate due to sepsis, that is, the survival rate.
또한, 염증 과정은 의래 병원성 인자에 대한 방어 기작이지만, 독성 물질의 자극이 없는 경우에도 통증을 유발할 수 있다. 국소적 염증 반응은 전염증성 사이토키닌을 방출시키고, 사이클로옥시제나제-2를 상향조절하여 프로스타글라딘을 합성시킨다. 이는 일차 구심성신경(Primary neurons)을 민감하게 하는데, 주변의 신경세포를 민감하게 함으로써 신경 면역을 활성화시킨다. 따라서, 긍극적으로 열적 또는 기계적 과민 현상(hypersensitivity)이 일어난다. 상기와 같은 염증반응이 일어나는 경우, 통증이 수반되는데 이러한 통증은 조직에 손상을 주거나 잠재적인 손상을 줄 수 있는 유해 자극에 의해 나타나는 일종의 경고성 감각인 통각(nociceptive pain)과 손상된 조직, 그 주변조직으로부터 활성화되어 분비되는 IL-1β(인터류킨1) 등의 염증성 매개물들이 유해 감수기에 작용하여 나타나는 염증성 통증(inflammatory pain) 그리고 말초와 중추 신경의 자체 손상으로 인해 유해하지 않은 자극에도 지속적으로 나타나는 신경병증성 통증(neuropathic pain)으로 구별될 수 있다.In addition, although the inflammatory process is a defense mechanism against medical pathogenic factors, it can cause pain even in the absence of stimulation by toxic substances. The local inflammatory response releases pro-inflammatory cytokinins and upregulates cyclooxygenase-2 to synthesize prostaglandins. This sensitizes primary afferent neurons, which activates neural immunity by sensitizing surrounding neurons. Consequently, thermal or mechanical hypersensitivity ultimately occurs. When the above inflammatory reaction occurs, pain is accompanied. This pain is a kind of warning sensation caused by noxious stimuli that can damage or potentially damage tissues, nociceptive pain, damaged tissues, and their surrounding tissues. Inflammatory pain, which occurs when inflammatory mediators such as IL-1β (interleukin 1), which are activated and secreted from the body, act on noxious receptors, and neuropathic pain, which persists even in spite of harmless stimulation due to self-damage of peripheral and central nerves. Pain (neuropathic pain) can be distinguished.
그러나, 패혈증과 마찬가지로, 염증반응 억제 효과가 있는 물질이 반드시 통증을 예방 또는 치료하는 효과를 나타내는 것은 아니다. 한 연구결과에 따르면, 비스테로이드성 소염통증제 중 하나인 멜록시캄(Meloxicam)이 생쥐의 개복술 후 COX-2 관련 항염증 효과가 있었으나, 통증에는 효과적이지 못하였음을 확인하여, 항염증 효과가 반드시 통증의 예방 또는 치료 효과로 이어지지 않는다는 것을 확인한 바 있다.However, similar to sepsis, a substance having an inflammatory response suppression effect does not necessarily have an effect of preventing or treating pain. According to one study, Meloxicam, one of the non-steroidal anti-inflammatory drugs, had an anti-inflammatory effect related to COX-2 after laparotomy in mice, but was not effective for pain. It has been confirmed that it does not necessarily lead to a preventive or therapeutic effect of pain.
한편, 향청란(Dracocephalum moldavica)은 중앙아시아, 중국 북부, 동유럽 및 중부 유럽에 서식하는 다년생의 식물로서, 일반적으로 몰다비카용머리(Moldavian dragonhead) 혹은 Moldavian balm이라고 부른다. 전통적으로 심혈관계 질병 치료에 동아시아 지역에서 사용되어왔으며, 항산화와 같은 약리학적 효과가 있음이 알려진 바 있다. 그러나, 지금까지 향청란 추출물의 패혈증 또는 염증성 통증의 치료 및 개선에 대해서는 전혀 시사 또는 개시된 바가 없다.On the other hand, fragrance orchid ( Dracocephalum moldavica ) is a perennial plant native to Central Asia, northern China, eastern and central Europe, and is commonly referred to as Moldavian dragonhead or Moldavian balm. Traditionally, it has been used in East Asia to treat cardiovascular diseases, and it is known to have pharmacological effects such as antioxidant. However, there has been no suggestion or disclosure of the treatment and improvement of sepsis or inflammatory pain with the extract of scented orchid so far.
이러한 배경 하에서, 본 발명자들은 체내의 과도한 염증반응을 개선하고 생존율을 개선시켜 패혈증의 예방 및 치료 효과를 나타내면서 부작용이 적은 천연물을 찾고자 예의 노력한 결과, 향청란 (Dracocephalum moldavica) 에탄올 추출물이 NO의 생성, COX2 또는 IL-6의 발현을 효과적으로 억제함으로써 패혈증 동물 모델에서 패혈증으로 인해 발생하는 사망률을 현저히 감소시키는 등의 패혈증의 예방 및 치료 효과를 확인하여, 본 발명을 완성하였다.Under this background, the present inventors have made efforts to find a natural product with fewer side effects while improving the excessive inflammatory response in the body and improving the survival rate to prevent and treat sepsis. Alternatively, the present invention was completed by confirming the preventive and therapeutic effects of sepsis, such as significantly reducing the mortality rate caused by sepsis in an animal model of sepsis by effectively inhibiting the expression of IL-6.
본 발명의 목적은 패혈증 또는 통증의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.An object of the present invention is to provide a pharmaceutical composition for preventing or treating sepsis or pain.
본 발명의 다른 목적은 패혈증 또는 통증의 예방 또는 개선용 건강기능식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a health functional food composition for preventing or improving sepsis or pain.
상기 목적을 달성하기 위하여,In order to achieve the above purpose,
본 발명은 향청란(Dracocephalum moldavica) 추출물을 유효성분으로 포함하는 패혈증 또는 통증의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating sepsis or pain, comprising an extract of Dracocephalum moldavica as an active ingredient.
또한, 본 발명은 향청란(Dracocephalum moldavica) 추출물을 유효성분으로 포함하는 패혈증 또는 통증의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving sepsis or pain, comprising an extract of Dracocephalum moldavica as an active ingredient.
본 발명의 향청란 추출물을 포함하는 조성물은 마우스 모델에서 패혈증으로 인해 증가된 염증성 사이토카인을 감소시킬뿐만 아니라, 패혈증에 의한 사망율을 감소시켜 생존율을 개선시키고, 염증성 통증 및 신경병증성 통증 반응을 감소시키는 효과를 나타냄을 확인함에 따라, 패혈증 또는 통증의 예방, 치료 또는 개선용 조성물로 유용할 수 있다.The composition containing the scented orchid extract of the present invention not only reduces the increased inflammatory cytokines due to sepsis in a mouse model, but also improves the survival rate by reducing the mortality rate due to sepsis, and reduces inflammatory pain and neuropathic pain response According to the confirmation of the effect, it may be useful as a composition for preventing, treating or improving sepsis or pain.
도 1은 RAW 264.7 세포 배양액에서 NO assay를 통해 본 발명의 향청란 추출물 처리에 따른 NO의 농도를 정량한 그래프이다.
도 2는 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포에서 iNOS의 mRNA 발현량을 RT-qPCR로 확인한 결과를 나타낸 그래프이다.
도 3은 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포에서 iNOS의 단백질 발현량을 확인하여 정량한 그래프이다.
도 4는 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포 배양액의 PGE2의 농도를 ELISA kit로 정량한 그래프이다.
도 5는 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포에서 COX-2의 mRNA 발현량을 RT-qPCR로 확인한 그래프이다.
도 6은 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포에서 COX-2의 단백질 발현량을 western blot으로 확인한 그래프이다.
도 7은 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포에서 IL-6의 mRNA 발현량을 RT-qPCR로 확인한 그래프이다.
도 8은 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포 배양액의 IL-6의 단백질 발현량을 ELISA kit로 정량한 그래프이다.
도 9는 마우스 모델을 이용하여 향청란 추출물의 항패혈증 효과를 확인하기 위한 실험 절차를 나타낸 것이다.
도 10은 본 발명의 향청란 추출물의 LPS 유도 패혈증 모델에서 생존율 증가 효과를 나타낸 그래프이다.
도 11은 본 발명의 향청란 추출물 처리에 따른 LPS 유도 패혈증 모델의 혈장내 IL-6 농도를 정량한 그래프이다.
도 12는 마우스 모델을 이용하여 향청란 추출물의 항통증 효과를 확인하기 위한 실험 절차를 나타낸 것이다.
도 13은 시간에 따른 통증 관련 행동 시간(sec)을 기록한 결과를 나타낸 그래프이다.
도 14는 향청란 추출물 처리에 따른 Phase Ⅰ과 Ⅱ에 해당하는 통증 관련 행동 시간을 합산하여 나타낸 그래프이다.Figure 1 is a graph quantifying the concentration of NO according to the treatment of the scented orchid extract of the present invention through NO assay in RAW 264.7 cell culture medium.
Figure 2 is a graph showing the results of confirming the mRNA expression level of iNOS in RAW 264.7 cells according to the treatment of the blue orchid extract of the present invention by RT-qPCR.
Figure 3 is a graph quantifying the protein expression of iNOS in RAW 264.7 cells according to the treatment of the blue orchid extract of the present invention.
Figure 4 is a graph quantifying the concentration of PGE 2 in the RAW 264.7 cell culture medium according to the treatment of the blue orchid extract of the present invention with an ELISA kit.
5 is a graph confirming the mRNA expression level of COX-2 in RAW 264.7 cells according to the treatment of the blue orchid extract of the present invention by RT-qPCR.
Figure 6 is a graph confirming the protein expression level of COX-2 in RAW 264.7 cells according to the treatment of the blue orchid extract of the present invention by western blot.
Figure 7 is a graph confirming the mRNA expression level of IL-6 in RAW 264.7 cells according to the treatment of the blue orchid extract of the present invention by RT-qPCR.
8 is a graph quantifying the protein expression level of IL-6 in RAW 264.7 cell culture medium according to the treatment of the blue orchid extract of the present invention with an ELISA kit.
Figure 9 shows an experimental procedure for confirming the anti-septic effect of the scented orchid extract using a mouse model.
Figure 10 is a graph showing the effect of increasing the survival rate in the LPS-induced sepsis model of the scented orchid extract of the present invention.
11 is a graph quantifying the concentration of IL-6 in plasma in the LPS-induced sepsis model according to the treatment with the blue orchid extract of the present invention.
Figure 12 shows an experimental procedure for confirming the anti-pain effect of the scented orchid extract using a mouse model.
13 is a graph showing the results of recording pain-related action time (sec) over time.
14 is a graph showing the sum of pain-related behavioral times corresponding to Phases I and II according to the treatment of the scented orchid extract.
이하, 본 발명의 실시예로 본 발명을 상세히 설명하기로 한다. 다만, 하기 실시예는 본 발명에 대한 예시로 제시되는 것으로, 당업자에게 주지 저명한 기술 또는 구성에 대한 구체적인 설명이 본 발명의 요지를 불필요하게 흐릴 수 있다고 판단되는 경우에는 그 상세한 설명을 생략할 수 있고, 이에 의해 본 발명이 제한되지는 않는다. 본 발명은 후술하는 특허 청구범위의 기재 및 그로부터 해석되는 균등 범주 내에서 다양한 변형 및 응용이 가능하다.Hereinafter, the present invention will be described in detail with examples of the present invention. However, the following examples are presented as examples of the present invention, and if it is determined that detailed descriptions of well-known techniques or configurations may unnecessarily obscure the gist of the present invention, the detailed descriptions may be omitted. , the present invention is not limited thereby. Various modifications and applications of the present invention are possible within the description of the claims described later and equivalent scopes interpreted therefrom.
또한, 본 명세서에서 사용되는 용어(terminology)들은 본 발명의 바람직한 실시예를 적절히 표현하기 위해 사용된 용어들로서, 이는 사용자, 운용자의 의도 또는 본 발명이 속하는 분야의 관례 등에 따라 달라질 수 있다. 따라서, 본 용어들에 대한 정의는 본 명세서 전반에 걸친 내용을 토대로 내려져야 할 것이다. In addition, the terms used in this specification (terminology) are terms used to appropriately express preferred embodiments of the present invention, which may vary according to the intention of a user or operator or customs in the field to which the present invention belongs. Therefore, definitions of these terms will have to be made based on the content throughout this specification.
본 발명에서 사용되는 모든 기술용어는, 달리 정의되지 않는 이상, 본 발명의 관련 분야에서 통상의 당업자가 일반적으로 이해하는 바와 같은 의미로 사용된다. 또한 본 명세서에는 바람직한 방법이나 시료가 기재되나, 이와 유사하거나 동등한 것들도 본 발명의 범주에 포함된다. 본 명세서에 참고문헌으로 기재되는 모든 간행물의 내용은 본 발명에 도입된다.All technical terms used in the present invention, unless defined otherwise, are used with the same meaning as commonly understood by one of ordinary skill in the art related to the present invention. In addition, although preferred methods or samples are described in this specification, those similar or equivalent thereto are also included in the scope of the present invention. The contents of all publications incorporated herein by reference are incorporated herein by reference.
본 발명에서 어떤 구성요소를 "포함"한다는 것은, 특별히 반대되는 기재가 없는 한 다른 구성요소를 제외하는 것이 아니라 다른 구성 요소를 더 포함할 수 있는 것을 의미한다.In the present invention, "include" a certain component means that other components may be further included without excluding other components unless otherwise stated.
패혈증 또는 통증 예방 또는 개선용 약학적 조성물Pharmaceutical composition for preventing or improving sepsis or pain
본 발명은 향청란(Dracocephalum moldavica) 추출물을 유효성분으로 포함하는 패혈증 또는 통증의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating sepsis or pain, comprising an extract of Dracocephalum moldavica as an active ingredient.
본 발명에서 사용되는 용어 "예방"은 본 발명의 조성물의 투여로 특정 질환 의 증상을 억제하거나 진행을 지연시키는 모든 행위를 의미한다.As used herein, the term "prevention" refers to any action that suppresses symptoms or delays the progression of a specific disease by administering the composition of the present invention.
본 발명에서 사용되는 용어 "치료"는 본 발명의 조성물의 투여로 특정 질환의 증상을 호전 또는 이롭게 변경시키는 모든 행위를 의미한다.The term "treatment" used in the present invention refers to all activities that improve or beneficially change the symptoms of a specific disease by administration of the composition of the present invention.
본 발명의 향청란 추출물은 패혈증으로 인해 증가된 염증성 사이토카인의 생성 또는 발현을 감소시킬뿐만 아니라, 패혈증에 의한 사망율을 감소시켜 생존율을 개선시키는 효과를 나타냄으로서 패혈증 예방 또는 치료 효과를 나타내는 것을 특징으로 한다.The scented orchid extract of the present invention not only reduces the production or expression of inflammatory cytokines that are increased due to sepsis, but also shows the effect of improving survival rate by reducing the mortality rate due to sepsis, thereby exhibiting the effect of preventing or treating sepsis. .
본 발명에 따른 약학적 조성물에 있어서, 상기 패혈증은 그람 음성균의 외막에 존재하는 지질다당류(Lipopolysaccharide)에 의해 유발되는 세균성 패혈증인 것일 수 있으나, 이에 제한되지는 않는다.In the pharmaceutical composition according to the present invention, the sepsis may be bacterial sepsis caused by lipopolysaccharide present in the outer membrane of Gram-negative bacteria, but is not limited thereto.
본 발명에 따른 약학적 조성물에 있어서, 상기 향청란 추출물은 패혈증으로 인한 사망율 증가를 감소시키는 것일 수 있다.In the pharmaceutical composition according to the present invention, the scented orchid extract may reduce the increase in mortality due to sepsis.
본 발명의 일실시예에서는, 본 발명에 따른 상기 향청란 추출물이 마우스 모델에서 패혈증에 의해 폭풍적으로 증가된 혈장내 염증 인자 IL-6 농도를 감소시킬뿐만 아니라, 패혈증으로 인한 사망률 증가를 억제하여 마우스의 생존율을 개선시킬 수 있음을 확인하였다(실험예 1 및 2 참조).In one embodiment of the present invention, the scented orchid extract according to the present invention not only reduces the concentration of the plasma inflammatory factor IL-6, which is dramatically increased by sepsis in a mouse model, but also suppresses the increase in mortality due to sepsis in mice It was confirmed that the survival rate of can be improved (see Experimental Examples 1 and 2).
본 발명에 따른 약학적 조성물에 있어서, 상기 향청란 추출물은 패혈증으로 인한 염증성 사이토카인의 생성 또는 발현 증가를 억제하여 패혈증 예방 또는 치료 효과를 나타내는 것일 수 있다. 이때, 상기 염증성 사이토카인은 염증성 사이토카인 및 염증 관련 인자들을 의미하는 것일 수 있고, 바람직하게는, NO(nitric oxide), PGE2, iNOS, COX-2 및 IL-6로 이루어진 군으로부터 선택되는 1종 이상인 것일 수 있다.In the pharmaceutical composition according to the present invention, the scented orchid extract may inhibit the production or increase in expression of inflammatory cytokines due to sepsis, thereby exhibiting an effect of preventing or treating sepsis. In this case, the inflammatory cytokine may mean inflammatory cytokines and inflammation-related factors, preferably, NO (nitric oxide), PGE 2 , iNOS, COX-2 and IL-6 selected from the group consisting of 1 There may be more than one species.
본 발명의 일실시예에서는, 본 발명에 따른 상기 향청란 추출물이 LPS에 의한 NO(nitric oxide), PGE2, iNOS, COX-2, 및 IL-6의 mRNA 또는 단백질 발현을 감소시키는 항염증 효과가 있음을 확인하였으며(실험예 1 참조), 마우스 모델에서 패혈증에 의해 폭풍적으로 증가된 혈장내 염증 인자 IL-6 농도를 감소시키는 효과가 있음을 확인하였다(실험예 2 참조).In one embodiment of the present invention, the anti-inflammatory effect of reducing the mRNA or protein expression of NO (nitric oxide), PGE 2 , iNOS, COX-2, and IL-6 caused by LPS of the scented blue orchid extract according to the present invention (See Experimental Example 1), and it was confirmed that there was an effect of reducing the concentration of the plasma inflammatory factor IL-6, which was drastically increased by sepsis in a mouse model (see Experimental Example 2).
본 발명의 향청란 추출물은 염증성 사이토카인 및 염증 관련 인자의 생성 또는 발현을 감소시킬뿐만 아니라, 통증 반응 자체를 억제하는 진통 효과를 나타냄으로써 통증의 예방 또는 치료 효과를 나타내는 것을 특징으로 한다.The scented orchid extract of the present invention is characterized in that it exhibits an analgesic effect of suppressing the pain response itself, as well as reducing the production or expression of inflammatory cytokines and inflammation-related factors, thereby exhibiting a preventive or therapeutic effect on pain.
본 발명에 따른 약학적 조성물에 있어서, 상기 통증은 물리적 자극 또는 화학적 자극에 의한 통증인 것일 수 있고, 바람직하게는, 염증성(inflammatory) 통증 또는 신경병증성(neuropathic) 통증인 것일 수 있다.In the pharmaceutical composition according to the present invention, the pain may be pain caused by physical stimulation or chemical stimulation, and preferably, may be inflammatory pain or neuropathic pain.
본 발명에 따른 약학적 조성물에 있어서, 상기 향청란 추출물은 염증성 사이토카인의 생성 또는 발현 증가를 억제하여 통증 예방 또는 치료 효과를 나타내는 것일 수 있다. 이때, 상기 염증성 사이토카인은 염증성 사이토카인 및 염증 관련 인자들을 의미하는 것일 수 있고, 바람직하게는, NO(nitric oxide), PGE2, iNOS, COX-2 및 IL-6로 이루어진 군으로부터 선택되는 1종 이상인 것일 수 있다.In the pharmaceutical composition according to the present invention, the scented orchid extract may inhibit the production or expression increase of inflammatory cytokines to exhibit pain prevention or treatment effects. In this case, the inflammatory cytokine may mean inflammatory cytokines and inflammation-related factors, preferably, NO (nitric oxide), PGE 2 , iNOS, COX-2 and IL-6 selected from the group consisting of 1 There may be more than one species.
본 발명의 일실시예에서는, 본 발명에 따른 상기 향청란 추출물이 LPS에 의한 NO(nitric oxide), PGE2, iNOS, COX-2, 및 IL-6의 mRNA 또는 단백질 발현을 감소시키는 항염증 효과가 있음을 확인하였다(실험예 1 참조).In one embodiment of the present invention, the anti-inflammatory effect of reducing the mRNA or protein expression of NO (nitric oxide), PGE 2 , iNOS, COX-2, and IL-6 caused by LPS of the scented blue orchid extract according to the present invention It was confirmed that there was (see Experimental Example 1).
본 발명에 따른 약학적 조성물에 있어서, 상기 향청란 추출물은 통증 반응을 억제하는 진통효과를 나타내는 것일 수 있다.In the pharmaceutical composition according to the present invention, the scented orchid extract may exhibit an analgesic effect of suppressing a pain response.
본 발명의 일실시예에서는, 본 발명에 따른 상기 향청란 추출물이 마우스 모델에서 약물반응으로 인해 유발된 염증성 통증 및 신경병증성 통증 관련 행동을 억제하는 진통 효과가 있음을 확인하였다(실험예 3 참조).In one embodiment of the present invention, it was confirmed that the scented orchid extract according to the present invention has an analgesic effect of suppressing inflammatory pain and neuropathic pain-related behaviors induced by drug reactions in a mouse model (see Experimental Example 3). .
본 발명에 따른 약학적 조성물에 있어서, 상기 향청란 추출물은 향청란 잎 또는 전초로부터 추출되는 것일 수 있다.In the pharmaceutical composition according to the present invention, the scented orchid extract may be extracted from scented orchid leaves or outposts.
본 발명에 따른 약학적 조성물에 있어서, 상기 향청란 추출물은 당업계에 공지된 추출 및 분리하는 방법을 사용하여 추출물을 분리 및 수득한 것을 사용할 수 있으며, 본 발명에서 정의된 추출물은 적절한 용매를 이용하여 상기의 방법으로 준비된 유효성분 원료를 그대로 또는 분말 상태로 분쇄하여 추출할 수 있다. 이때 추출물을 수득하기 위해 사용할 수 있는 적절한 용매로는 당업계에서 허용되는 용매라면 어느 것을 사용해도 무방하며, 물, 탄소수 1 내지 탄소수 4의 알코올 또는 이들의 혼합용매로 추출하여 추출물을 제조할 수 있다. 예를 들어, 정제수, 메탄올(methanol), 에탄올(ethanol), 프로판올(propanol), 이소프로판올(isopropanol), 부탄올(butanol) 등을 포함하는 탄소수 1 내지 4의 알코올, 아세톤(acetone), 에테르(ether), 벤젠(benzene), 클로로포름(chloroform), 에틸아세테이트(ethyl acetate), 메틸렌클로라이드(methylene chloride), 헥산(hexane) 및 시클로헥산(cyclohexane) 등의 각종 용매를 단독으로 혹은 혼합하여 사용할 수 있으나, 이에 제한되지는 않는다. 바람직하게는 바람직하게는 물 또는 에탄올로부터 선택되는 1종 이상의 추출용매를 사용하여 추출할 수 있고, 보다 바람직하게는 50-90% 에탄올 수용액을 이용하여 추출할 수 있고, 70% 에탄올 수용액을 이용하는 것이 가장 바람직하다.In the pharmaceutical composition according to the present invention, the scented orchid extract may be used by separating and obtaining the extract using an extraction and separation method known in the art, and the extract defined in the present invention is obtained by using an appropriate solvent The active ingredient raw material prepared by the above method can be extracted as it is or by pulverizing in a powder state. At this time, as an appropriate solvent that can be used to obtain the extract, any solvent acceptable in the art may be used, and the extract may be prepared by extracting with water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. . For example, alcohol having 1 to 4 carbon atoms including purified water, methanol, ethanol, propanol, isopropanol, butanol, acetone, and ether Various solvents such as benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane may be used alone or in combination, but Not limited. Preferably, it can be extracted using one or more extraction solvents selected from water or ethanol, more preferably, it can be extracted using 50-90% aqueous ethanol solution, and it is preferable to use 70% aqueous ethanol solution. most desirable
추출 방법으로는 열수추출법, 냉침추출법, 환류냉각추출법, 용매추출법, 수증기증류법, 초음파추출법, 용출법, 압착법 등의 방법 중 어느 하나를 선택하여 사용할 수 있다. 또한, 목적하는 추출물은 추가로 통상의 분획 공정을 수행할 수도 있으며, 통상의 정제 방법을 이용하여 정제될 수도 있다. 본 발명의 추출물의 제조방법에는 제한이 없으며, 공지되어 있는 어떠한 방법도 이용될 수 있다.As an extraction method, any one of methods such as hot water extraction, cold brew extraction, reflux cooling extraction, solvent extraction, steam distillation, ultrasonic extraction, elution, and compression may be selected and used. In addition, the desired extract may be additionally subjected to a conventional fractionation process or may be purified using a conventional purification method. There is no limitation on the preparation method of the extract of the present invention, and any known method may be used.
예를 들면, 본 발명의 조성물에 포함되는 추출물은 상기한 용매 추출법으로 추출된 1차 추출물을, 원심분리, 여과, 농축후 동결 건조하여 냉장실에 보관하면서 그대로 사용할 수도 있고, 상기 1차 추출물을 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조할 수 있다. 또한, 상기 1차 추출물을 실리카겔 컬럼 크로마토그래피(silica gel column chromatography), 박층 크로마토그래피(thin layer chromatography), 고성능 액체 크로마토그래피(high performance liquid chromatography)등과 같은 다양한 크로마토그래피를 이용하여 추가로 정제된 분획을 얻을 수도 있다. For example, the extract included in the composition of the present invention may be used as it is while storing the primary extract extracted by the solvent extraction method described above, centrifuged, filtered, and concentrated, then lyophilized and stored in a refrigerator, or the primary extract may be used as it is under reduced pressure. It can be prepared in a powder state by further processes such as distillation and freeze drying or spray drying. In addition, a fraction further purified from the primary extract using various chromatography methods such as silica gel column chromatography, thin layer chromatography, and high performance liquid chromatography. can also be obtained.
따라서 본 발명에 있어서 추출물은 추출, 분획 또는 정제의 각 단계에서 얻어지는 모든 추출액, 분획 및 정제물, 그들의 희석액, 농축액 또는 건조물을 모두 포함하는 개념이다.Therefore, in the present invention, the extract is a concept that includes all extracts, fractions, and purified products obtained in each step of extraction, fractionation, or purification, and dilutions, concentrates, or dried products thereof.
상기 약학적 조성물은 약학적으로 허용되는 담체를 추가로 포함할 수 있다. 상기에서 "약학적으로 허용되는"이란 생리학적으로 허용되고 인간에게 투여될 때, 통상적으로 위장 장애, 현기증 등과 같은 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 조성물을 말한다. 약학적으로 허용되는 담체로는, 예를 들면, 락토스, 전분, 셀룰로스 유도체, 마그네슘 스테아레이트, 스테아르산 등과 같은 경구투여용 담체 및 물, 적합한 오일, 식염수, 수성 글루코스 및 글리콜 등과 같은 비경구 투여용 담체 등이 있으며, 안정화제 및 보존제를 추가로 포함할 수 있다. 적합한 안정화제로는 아황산수소나트륨, 아황산나트륨 또는 아스코르브산과 같은 항산화제가 있다. 적합한 보존제로는 벤즈알코늄 클로라이드, 메틸- 또는 프로필-파라벤 및 클로로부탄올이 있다. 그 밖의 약학적으로 허용되는 담체로는 다음의 문헌에 기재되어 있는 것을 참고로 할 수 있다(Remington's Pharmaceutical Sciences, 19th ed, Mack Publishing Company, Easton, PA, 1995). The pharmaceutical composition may further include a pharmaceutically acceptable carrier. In the above, "pharmaceutically acceptable" refers to a composition that is physiologically acceptable and does not cause an allergic reaction such as gastrointestinal disorder, dizziness, or similar reaction when administered to humans. Pharmaceutically acceptable carriers include, for example, carriers for oral administration such as lactose, starch, cellulose derivatives, magnesium stearate, and stearic acid, and carriers for parenteral administration such as water, suitable oil, saline, aqueous glucose and glycol, etc. There are carriers and the like, and may further include a stabilizer and a preservative. Suitable stabilizers include antioxidants such as sodium bisulfite, sodium sulfite or ascorbic acid. Suitable preservatives include benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol. As other pharmaceutically acceptable carriers, reference may be made to those described in the following literature (Remington's Pharmaceutical Sciences, 19th ed, Mack Publishing Company, Easton, PA, 1995).
본 발명에 따른 약학 조성물은 상술한 바와 같은 약학적으로 허용되는 담체와 함께 당업계에 공지된 방법에 따라 적합한 형태로 제형화 될 수 있다. 즉, 본 발명의 약학 조성물은 공지의 방법에 따라 다양한 비경구 또는 경구 투여용 형태로 제조될 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 제조된다.The pharmaceutical composition according to the present invention may be formulated in a suitable form according to a method known in the art together with a pharmaceutically acceptable carrier as described above. That is, the pharmaceutical composition of the present invention can be prepared in various forms for parenteral or oral administration according to known methods. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
경구투여를 위한 고형 제제에는 정제, 환자, 산제, 과립제, 캡슐제, 트로키제 등이 포함되며, 이러한 고형 제제는 하나 이상의 본 발명의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로스(sucrose), 락토오스(lactose) 또는 젤라틴 등을 섞어 조제된다. 또한, 단순한 부형제 외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 또는 시럽제 등이 해당되는데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.Solid preparations for oral administration include tablets, patients, powders, granules, capsules, troches, etc., and these solid preparations contain one or more compounds of the present invention in at least one excipient, for example, starch, calcium carbonate, water It is prepared by mixing sucrose, lactose or gelatin. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, or syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. can
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁용제, 유제, 동결건조제제, 좌제 등이 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세롤, 젤라틴 등이 사용될 수 있다.Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspension solutions, emulsions, freeze-dried formulations, suppositories, and the like. 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 suppositories, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerol, gelatin, and the like may be used.
상기 약학적 조성물은 담체, 부형제 또는 희석제를 더 포함할 수 있다. 담체, 부형제, 또는 희석제는 예를 들어, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알기네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로스, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트, 또는 광물유를 포함할 수 있다.The pharmaceutical composition may further include a carrier, excipient or diluent. Carriers, excipients, or diluents include, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginates, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil.
본 발명의 약학 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명의 용어, "투여"란 적절한 방법으로 개체에게 소정의 물질을 도입하는 것을 의미하며, 상기 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한, 어떠한 일반적인 경로를 통하여 투여될 수 있다. 복강내 투여, 정맥내 투여, 근육내 투여, 피하 투여, 피내 투여, 경구 투여, 국소 투여, 비내 투여, 폐내 투여, 직장내 투여, 뇌혈관내 투여될 수 있으나, 이에 한정되는 것은 아니다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term "administration" means introducing a predetermined substance into a subject by an appropriate method, and the administration route of the composition may be administered through any general route as long as it can reach the target tissue. Intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, intranasal administration, intrapulmonary administration, intrarectal administration, intracerebrovascular administration may be administered, but is not limited thereto.
상기 용어, "개체"란 인간을 포함한 쥐, 생쥐, 가축 등의 모든 동물을 의미한다. 바람직하게는, 인간을 포함한 포유동물일 수 있다.The term "individual" refers to all animals such as rats, mice, livestock, and the like, including humans. Preferably, it may be a mammal including a human.
상기 용어, "약학적으로 유효한 양"이란 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며, 부작용을 일으키지 않을 정도의 양을 의미하며, 유효 용량 수준은 환자의 성별, 연령, 체중, 건강 상태, 질병의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로, 및 배출 비율, 치료 기간, 배합 또는 동시에 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 당업자에 의해 용이하게 결정될 수 있다. 일반적으로 약 0.001~100 mg/kg/day이며, 바람직하게는 0.01~35 mg/kg/day이다. 몸무게가 70kg인 성인 환자를 기준으로 할 때, 일반적으로 0.07~7000 mg/day이며, 바람직하게는 0.7~2500 mg/day이며, 투여는 상기 권장 투여량을 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다.The term "pharmaceutically effective amount" means an amount that is sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects, and the effective dose level is determined by the sex and age of the patient. , weight, health condition, type of disease, severity, activity of drug, sensitivity to drug, method of administration, time of administration, route of administration, and rate of excretion, duration of treatment, factors including drugs used in combination or concurrently, and other medical fields It can be easily determined by a person skilled in the art according to well-known factors. It is generally about 0.001 to 100 mg/kg/day, preferably 0.01 to 35 mg/kg/day. Based on an adult patient weighing 70 kg, it is generally 0.07 to 7000 mg/day, preferably 0.7 to 2500 mg/day, and the recommended dose may be administered once a day or divided several times. may also be administered.
본 발명의 조성물은 패혈증 또는 통증의 예방 또는 치료를 위하여 단독으로, 또는 수술, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The composition of the present invention can be used alone or in combination with methods using surgery, hormone therapy, chemotherapy, and biological response modifiers for the prevention or treatment of sepsis or pain.
패혈증 또는 통증 예방 또는 개선용 건강기능식품 조성물Health functional food composition for preventing or improving sepsis or pain
본 발명은 향청란(Dracocephalum moldavica) 추출물을 유효성분으로 포함하는 패혈증 또는 통증의 예방 또는 개선용 건강기능식품 조성물을 제공한다.The present invention provides a health functional food composition for preventing or improving sepsis or pain, comprising an extract of Dracocephalum moldavica as an active ingredient.
본 발명에서 사용되는 용어 "개선"은 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다.As used herein, the term "improvement" refers to any action that at least reduces a parameter associated with the condition being treated, eg, the severity of a symptom.
본 발명에서 사용되는 용어 "건강기능식품"이란 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 정제, 캡슐제, 환제, 액제, 분말 또는 과립 등의 형태로 제조 및 가공한 식품을 말한다. 여기서 '기능성'이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 건강기능식품은 통상의 기술분야에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조시에는 통상의 기술분야에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한, 상기 건강기능식품의 제형 또한 건강기능식품으로 인정되는 제형이면 제한없이 제조될 수 있다. 본 발명의 건강기능식품 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품 유래 성분을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 본 발명의 건강기능식품은 패혈증 치료제의 효과를 증진시키기 위한 보조제로 섭취가 가능하다.The term "health functional food" used in the present invention refers to food prepared and processed in the form of tablets, capsules, pills, liquids, powders or granules using raw materials or ingredients having useful functionalities for the human body. Here, 'functionality' means obtaining useful effects for health purposes, such as adjusting nutrients for the structure and function of the human body or physiological functions. The health functional food of the present invention can be manufactured by a method commonly used in the conventional technical field, and can be prepared by adding raw materials and components commonly added in the conventional technical field at the time of manufacture. In addition, the formulation of the health functional food may also be manufactured without limitation as long as the formulation is recognized as a health functional food. The health functional food composition of the present invention can be prepared in various types of formulations, and unlike general drugs, it has the advantage of using food-derived ingredients as raw materials and has no side effects that may occur when taking drugs for a long time, and has excellent portability. , The health functional food of the present invention can be consumed as an adjuvant to enhance the effectiveness of sepsis treatment.
또한, 본 발명은 향청란(Dracocephalum moldavica) 추출물을 유효성분으로 포함하는 패혈증 또는 통증의 예방 또는 개선용 건강식품 조성물을 제공한다.In addition, the present invention provides a health food composition for preventing or improving sepsis or pain, comprising an extract of Dracocephalum moldavica as an active ingredient.
본 발명의 상기 향청란 추출물은 패혈증으로 인해 증가된 염증성 사이토카인의 생성 또는 발현을 감소시킬뿐만 아니라, 패혈증에 의한 사망율을 감소시켜 생존율을 개선시키는 효과를 나타냄으로써 패혈증 예방 또는 개선 효과를 나타내는 것을 특징으로 한다.The scented orchid extract of the present invention not only reduces the production or expression of inflammatory cytokines increased due to sepsis, but also exhibits an effect of improving survival rate by reducing mortality rate due to sepsis, thereby exhibiting an effect of preventing or improving sepsis. do.
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물에 있어서, 상기 패혈증은 그람 음성균의 외막에 존재하는 지질다당류(Lipopolysaccharide)에 의해 유발되는 세균성 패혈증인 것일 수 있으나, 이에 제한되지는 않는다.In the health functional food composition or health food composition according to the present invention, the sepsis may be bacterial sepsis caused by lipopolysaccharide present in the outer membrane of Gram-negative bacteria, but is not limited thereto.
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물에 있어서, 상기 향청란 추출물은 패혈증으로 인한 사망율 증가를 감소시키는 것일 수 있다.In the health functional food composition or health food composition according to the present invention, the scented orchid extract may reduce the increase in mortality due to sepsis.
본 발명의 일실시예에서는, 본 발명에 따른 상기 향청란 추출물이 마우스 모델에서 패혈증에 의해 폭풍적으로 증가된 혈장내 염증 인자 IL-6 농도를 감소시킬뿐만 아니라, 패혈증으로 인한 사망률 증가를 억제하여 마우스의 생존율을 개선시킬 수 있음을 확인하였다(실험예 1 및 2 참조).In one embodiment of the present invention, the scented orchid extract according to the present invention not only reduces the concentration of the plasma inflammatory factor IL-6, which is dramatically increased by sepsis in a mouse model, but also suppresses the increase in mortality due to sepsis in mice It was confirmed that the survival rate of can be improved (see Experimental Examples 1 and 2).
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물에 있어서, 상기 향청란 추출물은 패혈증으로 인한 염증성 사이토카인의 생성 또는 발현 증가를 억제하여 패혈증 예방 또는 치료 효과를 나타내는 것일 수 있다. 이때, 상기 염증성 사이토카인은 염증성 사이토카인 및 염증 관련 인자들을 의미하는 것일 수 있고, 바람직하게는, NO(nitric oxide), PGE2, iNOS, COX-2 및 IL-6로 이루어진 군으로부터 선택되는 1종 이상인 것일 수 있다.In the health functional food composition or health food composition according to the present invention, the scented egg extract may inhibit the production or increase in expression of inflammatory cytokines due to sepsis, thereby exhibiting an effect of preventing or treating sepsis. In this case, the inflammatory cytokine may mean inflammatory cytokines and inflammation-related factors, preferably, NO (nitric oxide), PGE 2 , iNOS, COX-2 and IL-6 selected from the group consisting of 1 There may be more than one species.
본 발명의 일실시예에서는, 본 발명에 따른 상기 향청란 추출물이 LPS에 의한 NO(nitric oxide), PGE2, iNOS, COX-2, 및 IL-6의 mRNA 또는 단백질 발현을 감소시키는 항염증 효과가 있음을 확인하였으며(실험예 1 참조), 마우스 모델에서 패혈증에 의해 증가된 혈장내 염증 인자 IL-6 농도를 감소시키는 효과가 있음을 확인하였다(실험예 2 참조).In one embodiment of the present invention, the anti-inflammatory effect of reducing the mRNA or protein expression of NO (nitric oxide), PGE 2 , iNOS, COX-2, and IL-6 caused by LPS of the scented blue orchid extract according to the present invention (see Experimental Example 1), and it was confirmed that there was an effect of reducing the concentration of the inflammatory factor IL-6 in plasma increased by sepsis in a mouse model (see Experimental Example 2).
본 발명의 향청란 추출물은 염증성 사이토카인 및 염증 관련 인자의 생성 또는 발현을 감소시킬뿐만 아니라, 통증 반응 자체를 억제하는 진통 효과를 나타냄으로써 통증의 예방 또는 개선 효과를 나타내는 것을 특징으로 한다.The scented orchid extract of the present invention is characterized in that it exhibits an analgesic effect of suppressing the pain response itself, as well as reducing the production or expression of inflammatory cytokines and inflammation-related factors, thereby preventing or ameliorating pain.
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물에 있어서, 상기 통증은 물리적 자극 또는 화학적 자극에 의한 통증인 것일 수 있고, 바람직하게는, 염증성(inflammatory) 통증 또는 신경병증성(neuropathic) 통증인 것일 수 있다.In the health functional food composition or health food composition according to the present invention, the pain may be pain caused by physical or chemical stimulation, preferably inflammatory pain or neuropathic pain. can
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물에 있어서, 상기 향청란 추출물은 염증성 사이토카인의 생성 또는 발현 증가를 억제하여 통증 예방 또는 개선 효과를 나타내는 것일 수 있다. 이때, 상기 염증성 사이토카인은 염증성 사이토카인 및 염증 관련 인자들을 의미하는 것일 수 있고, 바람직하게는, NO(nitric oxide), PGE2, iNOS, COX-2 및 IL-6로 이루어진 군으로부터 선택되는 1종 이상인 것일 수 있다.In the health functional food composition or health food composition according to the present invention, the scented orchid extract may inhibit the production or expression increase of inflammatory cytokines to prevent or improve pain. In this case, the inflammatory cytokine may mean inflammatory cytokines and inflammation-related factors, preferably, NO (nitric oxide), PGE 2 , iNOS, COX-2 and IL-6 selected from the group consisting of 1 There may be more than one species.
본 발명의 일실시예에서는, 본 발명에 따른 상기 향청란 추출물이 LPS에 의한 NO(nitric oxide), PGE2, iNOS, COX-2, 및 IL-6의 mRNA 또는 단백질 발현을 감소시키는 항염증 효과가 있음을 확인하였다(실험예 1 참조).In one embodiment of the present invention, the anti-inflammatory effect of reducing the mRNA or protein expression of NO (nitric oxide), PGE 2 , iNOS, COX-2, and IL-6 caused by LPS of the scented blue orchid extract according to the present invention It was confirmed that there was (see Experimental Example 1).
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물에 있어서, 상기 향청란 추출물은 통증 반응을 억제하는 진통효과를 나타내는 것일 수 있다.In the health functional food composition or health food composition according to the present invention, the scented orchid extract may exhibit an analgesic effect of suppressing a pain response.
본 발명의 일실시예에서는, 본 발명에 따른 상기 향청란 추출물이 마우스 모델에서 약물반응으로 인해 유발된 염증성 통증 및 신경병증성 통증 관련 행동을 억제하는 진통 효과가 있음을 확인하였다(실험예 3 참조).In one embodiment of the present invention, it was confirmed that the scented orchid extract according to the present invention has an analgesic effect of suppressing inflammatory pain and neuropathic pain-related behaviors induced by drug reactions in a mouse model (see Experimental Example 3). .
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물에 있어서, 상기 향청란 추출물은 향청란 잎 또는 전초로부터 추출되는 것일 수 있다.In the health functional food composition or health food composition according to the present invention, the scented orchid extract may be extracted from scented orchid leaves or outposts.
본 발명에 따른 건강기능식품 조성물 또는 건강식품 조성물에 있어서, 상기 향청란 추출물은 당업계에 공지된 추출 및 분리하는 방법을 사용하여 추출물을 분리 및 수득한 것을 사용할 수 있으며, 본 발명에서 정의된 추출물은 적절한 용매를 이용하여 상기의 방법으로 준비된 유효성분 원료를 그대로 또는 분말 상태로 분쇄하여 추출할 수 있다. 이때 추출물을 수득하기 위해 사용할 수 있는 적절한 용매로는 당업계에서 허용되는 용매라면 어느 것을 사용해도 무방하며, 물, 탄소수 1 내지 탄소수 4의 알코올 또는 이들의 혼합용매로 추출하여 추출물을 제조할 수 있다. 예를 들어, 정제수, 메탄올(methanol), 에탄올(ethanol), 프로판올(propanol), 이소프로판올(isopropanol), 부탄올(butanol) 등을 포함하는 탄소수 1 내지 4의 알코올, 아세톤(acetone), 에테르(ether), 벤젠(benzene), 클로로포름(chloroform), 에틸아세테이트(ethyl acetate), 메틸렌클로라이드(methylene chloride), 헥산(hexane) 및 시클로헥산(cyclohexane) 등의 각종 용매를 단독으로 혹은 혼합하여 사용할 수 있으나, 이에 제한되지는 않는다. 바람직하게는 바람직하게는 물 또는 에탄올로부터 선택되는 1종 이상의 추출용매를 사용하여 추출할 수 있고, 보다 바람직하게는 50-90% 에탄올 수용액을 이용하여 추출할 수 있고, 70% 에탄올 수용액을 이용하는 것이 가장 바람직하다.In the health functional food composition or health food composition according to the present invention, the scented orchid extract may be used to separate and obtain an extract using an extraction and separation method known in the art, and the extract defined in the present invention Using an appropriate solvent, the active ingredient raw material prepared in the above method can be extracted as it is or by pulverizing in a powder state. At this time, as an appropriate solvent that can be used to obtain the extract, any solvent acceptable in the art may be used, and the extract may be prepared by extracting with water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. . For example, alcohol having 1 to 4 carbon atoms including purified water, methanol, ethanol, propanol, isopropanol, butanol, acetone, and ether Various solvents such as benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane may be used alone or in combination, but Not limited. Preferably, it can be extracted using one or more extraction solvents selected from water or ethanol, more preferably, it can be extracted using 50-90% aqueous ethanol solution, and it is preferable to use 70% aqueous ethanol solution. most desirable
본 발명에 따른 상기 건강기능식품 조성물 또는 건강식품 조성물은 패혈증을 예방 또는 개선시키기 위한 목적으로 상기 향청란 추출물을 식품, 음료 등의 건강기능식품 또는 건강식품에 첨가한 것일 수 있다.The health functional food composition or health food composition according to the present invention may be one in which the scented egg extract is added to a health functional food or health food such as food or beverage for the purpose of preventing or improving sepsis.
상기 식품의 종류에는 특별한 제한은 없다. 본 발명에 따른 향청란 추출물을 첨가할 수 있는 식품의 예로는 드링크제, 육류, 소시지, 빵, 비스킷, 떡, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 알코올 음료 및 비타민 복합제, 유제품 및 유가공 제품 등이 있으며, 통상적인 의미에서의 건강식품 및 건강기능식품을 모두 포함한다.There is no particular limitation on the type of food. Examples of foods to which the flavored orchid extract according to the present invention can be added include drinks, meat, sausages, bread, biscuits, rice cakes, chocolates, candies, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice creams , various soups, beverages, alcoholic beverages and vitamin complexes, dairy products and milk-processed products, etc., and include both health foods and health functional foods in a conventional sense.
본 발명에 따른 건강식품 및 건강기능식품 조성물은 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 본 발명에 따른 상기 향청란 추출물의 혼합량은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강식품 및 건강기능식품 중의 상기 향청란 추출물의 양은 전체 식품 중량의 0.1 내지 90 중량부로 가할 수 있다. 그러나 건강 유지를 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.The health food and health functional food composition according to the present invention may be added to food as it is or used together with other foods or food ingredients, and may be appropriately used according to conventional methods. The mixing amount of the scented orchid extract according to the present invention may be suitably determined according to its purpose of use (for prevention or improvement). In general, the amount of the scented orchid extract in health food and health functional food may be added in an amount of 0.1 to 90 parts by weight based on the total weight of the food. However, in the case of long-term intake for the purpose of health maintenance or health control, 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 greater than the above range.
본 발명의 건강식품 및 건강기능식품 조성물은 지시된 비율로 필수 성분으로서 본 발명에 따른 향청란 추출물을 함유하는 외에는 다른 성분에는 특별한 제한이 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 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트라이톨 등의 당알코올이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 건강기능성 식품 조성물 100 g당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health food and health functional food composition of the present invention is not particularly limited in other components except for containing the scented orchid extract according to the present invention as an essential component in the indicated ratio, and various flavoring agents or natural carbohydrates are added as in conventional beverages. It can be contained as a component. Examples of the aforementioned natural carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (thaumatin, stevia extract (eg rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can advantageously be used. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 g of the health functional food composition of the present invention.
상기 외에 본 발명에 따른 향청란 추출물을 함유하는 건강식품 및 건강기능식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 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 본 발명의 건강식품 및 건강기능식품 조성물은 천연 과일쥬스 및 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다.In addition to the above, the health food and health functional food composition containing the blue orchid extract according to the present invention are various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants, and enhancers (cheese, chocolate) etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like. In addition, the health food and health functional food composition of the present invention may contain fruit flesh for preparing natural fruit juice, fruit juice beverages, and vegetable beverages.
이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 유효물질을 함유하는 건강식품 및 건강기능식품 조성물 100 중량부 당 0.1 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.These components may be used independently or in combination. The ratio of these additives is not so critical, but is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the health food and health functional food composition containing the active substance of the present invention.
이하, 본 발명을 하기의 실시예에 의하여 더욱 상세하게 설명한다. 단, 하기의 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기의 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail by the following examples. However, the following examples are merely illustrative of the present invention, and the contents of the present invention are not limited by the following examples.
<실시예 1> 향청란 추출물의 제조<Example 1> Preparation of scented orchid extract
건조된 향청란(Dracocephalum moldavica)을 구입(내몽고몽약고분유한공사, 중국 내몽고 퉁랴오시)하여 전초를 분쇄기(mixer)를 이용하여 극세말하였다. 상기 극세말한 분말에 70% 에탄올 10배량(v/v)을 가하여 60℃에서 초음파 추출장치(POWERSONIC 410, 화신테크)로 2시간 동안 2회 추출하였다. 추출액을 filter paper (110mmØ, whatman)를 이용하여 감압여과 후, 감압농축기(NE-1001, EYELA)로 감압 농축하고, 동결건조기(FDU-2200, EYELA)로 동결건조하여 향청란 추출물 분말을 얻었다. 동결 건조한 분말을 -70℃ 냉동고에 보관하고, 실험시 0.9% 생리식염수에 녹여 사용하였다. 향청란 추출물의 수득률은 11.98%였다.Dried Hyangcheong orchid ( Dracocephalum moldavica ) was purchased (Inner Mongolia Mongolian Medicine Co., Ltd., Tongliao City, Inner Mongolia, China), and the outpost was finely ground using a mixer. 10 times (v/v) of 70% ethanol was added to the ultrafine powder and extracted twice for 2 hours at 60° C. with an ultrasonic extraction device (POWERSONIC 410, Hwashin Tech). The extract was filtered under reduced pressure using filter paper (110mmØ, whatman), concentrated under reduced pressure with a vacuum concentrator (NE-1001, EYELA), and lyophilized with a freeze dryer (FDU-2200, EYELA) to obtain a blue orchid extract powder. The lyophilized powder was stored in a -70°C freezer and used after being dissolved in 0.9% physiological saline during experiments. The yield of the blue orchid extract was 11.98%.
<실험예 1> 향청란 추출물의 항염증 효과<Experimental Example 1> Anti-inflammatory effect of scented orchid extract
본 발명의 향청란 추출물의 항염증 효과를 확인하기 위해 마우스 대식세포인 RAW 264.7 세포에 실시예 1의 향청란 추출물 (50, 100, 200 μg/mL)을 전처리 하였다. 1시간 뒤에 Lipopolysaccharide (LPS) 1 μg/mL를 처리하여 염증을 유도하였다. LPS 처리 24시간 후 세포의 배양액을 수거하여 NO, PGE2 및 IL-6의 농도를 정량하였다. 또한, 세포를 수거하여 RT-qPCR을 이용하여 mRNA 수준의 iNOS와 COX-2, IL-6의 변화를 확인하였고, western blot으로 단백질 수준의 iNOS와 COX-2의 변화를 확인하였다. In order to confirm the anti-inflammatory effect of the Blue Orchid extract of the present invention, RAW 264.7 cells, which are mouse macrophages, were pretreated with the Blue Orchid extract (50, 100, 200 μg/mL) of Example 1. After 1 hour, inflammation was induced by treatment with 1 μg/mL of Lipopolysaccharide (LPS). After 24 hours of LPS treatment, the cell culture medium was collected and the concentrations of NO, PGE 2 and IL-6 were quantified. In addition, the cells were harvested and RT-qPCR was used to confirm changes in iNOS, COX-2, and IL-6 at the mRNA level, and changes in iNOS and COX-2 at the protein level were confirmed by western blot.
도 1은 RAW 264.7 세포 배양액에서 NO assay를 통해 본 발명의 향청란 추출물 처리에 따른 NO의 농도를 정량한 그래프이다. LPS로 NO의 농도가 증가하였고 본 발명의 향청란 추출물을 전처리 하였을 때 농도 의존적으로 NO의 생성량을 감소시키는 것을 확인하였다.Figure 1 is a graph quantifying the concentration of NO according to the treatment of the scented orchid extract of the present invention through NO assay in RAW 264.7 cell culture medium. The concentration of NO increased with LPS, and it was confirmed that the amount of NO produced was decreased in a concentration-dependent manner when the scented orchid extract of the present invention was pretreated.
도 2는 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포에서 iNOS의 mRNA 발현량을 RT-qPCR로 확인한 결과를 나타낸 그래프이다. NO를 생성하는 효소인 iNOS의 mRNA 발현량이 LPS에 의해 유의적으로 증가하였고, 본 발명의 향청란 추출물의 전처리로 유의적으로 감소하는 것을 확인하였다.Figure 2 is a graph showing the results of confirming the mRNA expression level of iNOS in RAW 264.7 cells according to the treatment of the blue orchid extract of the present invention by RT-qPCR. It was confirmed that the mRNA expression level of iNOS, an enzyme that produces NO, was significantly increased by LPS and significantly decreased by pretreatment with the scented orchid extract of the present invention.
도 3은 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포에서 iNOS의 단백질 발현량을 확인하여 정량한 그래프이다. LPS로 iNOS의 단백질 발현량이 유의적으로 증가하였고, 본 발명의 향청란 추출물의 전처리로 유의적으로 감소하는 것을 확인하였다.Figure 3 is a graph quantifying the protein expression of iNOS in RAW 264.7 cells according to the treatment of the blue orchid extract of the present invention. It was confirmed that the protein expression level of iNOS was significantly increased by LPS, and significantly decreased by the pretreatment of the scented orchid extract of the present invention.
도 4는 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포 배양액의 PGE2의 농도를 ELISA kit로 정량한 그래프이다. LPS로 인해 PGE2의 농도가 증가하였고 본 발명의 향청란 추출물을 전처리 하였을 때 농도 의존적으로 PGE2의 생성량을 감소시키는 것을 확인하였다. Figure 4 is a graph quantifying the concentration of PGE 2 in the RAW 264.7 cell culture medium according to the treatment of the blue orchid extract of the present invention with an ELISA kit. The concentration of PGE 2 increased due to LPS, and it was confirmed that the amount of PGE 2 produced was decreased in a concentration-dependent manner when the scented orchid extract of the present invention was pretreated.
도 5는 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포에서 COX-2의 mRNA 발현량을 RT-qPCR로 확인한 그래프이다. PGE2를 생성하는 효소인 COX-2의 mRNA 발현량이 LPS로 인해 유의적으로 증가하였고, 본 발명의 향청란 추출물 200 μg/mL이상 전처리하였을 때, 유의적으로 감소하는 것을 확인하였다.5 is a graph confirming the mRNA expression level of COX-2 in RAW 264.7 cells according to the treatment of the blue orchid extract of the present invention by RT-qPCR. It was confirmed that the mRNA expression level of COX-2, an enzyme that produces PGE 2 , was significantly increased by LPS, and significantly decreased when pre-treated with 200 μg/mL or more of the scented orchid extract of the present invention.
도 6은 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포에서 COX-2의 단백질 발현량을 western blot으로 확인한 그래프이다. LPS로 COX-2의 단백질 발현량이 유의적으로 증가하였고, 본 발명의 향청란 추출물 200 μg/mL이상 전처리하였을 때, 유의적으로 감소하는 것을 확인하였다. Figure 6 is a graph confirming the protein expression level of COX-2 in RAW 264.7 cells according to the treatment of the blue orchid extract of the present invention by western blot. It was confirmed that the protein expression level of COX-2 was significantly increased by LPS, and significantly decreased when pre-treated with 200 μg/mL or more of the scented orchid extract of the present invention.
도 7은 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포에서 IL-6의 mRNA 발현량을 RT-qPCR로 확인한 그래프이다. 본 발명의 향청란 추출물이 LPS로 유도된 염증성 사이토카인인 IL-6의 mRNA 발현을 농도 의존적으로 억제하는 것을 확인하였다.Figure 7 is a graph confirming the mRNA expression level of IL-6 in RAW 264.7 cells according to the treatment of the blue orchid extract of the present invention by RT-qPCR. It was confirmed that the scented orchid extract of the present invention inhibited the LPS-induced inflammatory cytokine IL-6 mRNA expression in a concentration-dependent manner.
도 8은 본 발명의 향청란 추출물 처리에 따른 RAW 264.7 세포 배양액의 IL-6의 단백질 발현량을 ELISA kit로 정량한 그래프이다. LPS로 유도된 IL-6의 발현 증가는 본 발명의 향청란 추출물에 의해 농도 의존적으로 감소하였다.8 is a graph quantifying the protein expression level of IL-6 in RAW 264.7 cell culture medium according to the treatment of the blue orchid extract of the present invention with an ELISA kit. The increase in the expression of IL-6 induced by LPS was decreased in a concentration-dependent manner by the C. blue orchid extract of the present invention.
결과적으로, 본 발명의 향청란 추출물은 염증성 사이토카인 및 염증 관련 인자들의 mRNA 발현 및 단백질 발현을 감소시키는 항염증 효과가 있음을 확인하였다.As a result, it was confirmed that the scented orchid extract of the present invention has an anti-inflammatory effect by reducing mRNA expression and protein expression of inflammatory cytokines and inflammation-related factors.
<준비예 1> 실험 동물 준비<Preparation Example 1> Preparation of experimental animals
수컷 CD1-ICR 마우스(5주령, 25-30g)를 Charles River Laboratories(한국 서울)의 Orient Co. Ltd.에서 구입하여, 마우스를 케이지당 5 그룹으로 수용하고, 일정한 온도(23±1℃) 및 상대 습도(60±10%)에서 12시간 명/암주기(07:00~19:00에 점등)를 유지하면서 음식 및 물을 자유롭게 제공하였다. 동물 처리 및 유지 관리는 실험실 동물 관리 원칙(NIH 공보 번호 85-23, 1985년 개정)과 대한민국 강원대학교 동물실험윤리위원회(KW-200128-1)에 따라 수행하였다.Male CD1-ICR mice (5 weeks old, 25-30 g) were grown at Orient Co. Charles River Laboratories (Seoul, Korea). Ltd., mice were housed in 5 groups per cage, and maintained at a constant temperature (23±1°C) and relative humidity (60±10%) for 12 hours light/dark cycle (lights on from 07:00 to 19:00). ), food and water were provided ad libitum. Animal handling and maintenance were performed in accordance with the Principles for Laboratory Animal Care (NIH Publication No. 85-23, revised 1985) and the Animal Experimentation Ethics Committee of Kangwon National University, Republic of Korea (KW-200128-1).
<실험예 2> 향청란 추출물의 항패혈증 효과<Experimental Example 2> Anti-septic effect of scented orchid extract
본 발명의 향청란 추출물의 항패혈증 효과를 확인하기 위해 5주령 수컷 ICR 마우스에게 향청란 추출물 (50, 100, 200 mg/kg)을 함께 7일간 경구투여 하였다. 8일차에 Lipopolysaccharide (LPS) 25 mg/kg를 복강투여하여 패혈증을 유도하였다. 항패혈증 효과를 확인하기 위한 실험 절차는 도 9에 나타난 바와 같으며, 각 실험그룹당 투여 조건은 하기 표 1에 나타난 바와 같이 처리하였다. 대조군으로는 향청란 추출물 대신 식염수(9% saline)를 투여하였고, 실험그룹은 각 군당 12마리씩 총 6개 군으로 하였다. 각 군당 8마리는 12시간 간격으로 최대 72시간 생존율을 확인하여 표 1 및 도 10에 나타내었다. 또한, 각 군당 4마리는 희생시켜 배대정맥에서 채혈하여 혈장내 염증 물질인 IL-6를 정량하여 도 11에 나타내었다.To confirm the anti-septic effect of the anti-septic orchid extract of the present invention, 5-week-old male ICR mice were orally administered with the anti-septic orchid extract (50, 100, 200 mg/kg) for 7 days. On day 8, sepsis was induced by intraperitoneal administration of 25 mg/kg of Lipopolysaccharide (LPS). The experimental procedure for confirming the anti-septic effect is as shown in FIG. 9, and the administration conditions for each experimental group were treated as shown in Table 1 below. As a control group, saline (9% saline) was administered instead of the blue orchid extract, and the experimental group consisted of 6 groups with 12 animals in each group. Eight animals in each group were shown in Table 1 and FIG. 10 by checking the maximum 72-hour survival rate at 12-hour intervals. In addition, 4 rats per group were sacrificed, blood was collected from the abdominal vena cava, and IL-6, an inflammatory substance in plasma, was quantified and shown in FIG. 11 .
도 10은 본 발명의 향청란 추출물의 LPS 유도 패혈증 모델에서 생존율 증가 효과를 나타낸 그래프이다. 실험 결과, 향청란 추출물의 처리 농도가 높아질수록 대조군 대비 생존율이 현저하게 증가하는 것을 확인하였다.Figure 10 is a graph showing the effect of increasing the survival rate in the LPS-induced sepsis model of the scented orchid extract of the present invention. As a result of the experiment, it was confirmed that the survival rate compared to the control group significantly increased as the treatment concentration of the scented orchid extract increased.
도 11은 본 발명의 향청란 추출물 처리에 따른 LPS 유도 패혈증 모델의 혈장내 IL-6 농도를 정량한 그래프이다. LPS에 의해 혈장내 IL-6의 농도가 유의적으로 증가하였고, 본 발명의 향청란 추출물을 7일간 경구투여 한 그룹에서 유의적으로 감소시키는 것을 확인하였다.11 is a graph quantifying the concentration of IL-6 in plasma in the LPS-induced sepsis model according to the treatment with the blue orchid extract of the present invention. The concentration of IL-6 in plasma was significantly increased by LPS, and it was confirmed that the concentration of IL-6 in plasma was significantly decreased in the group orally administered with the flavored orchid extract of the present invention for 7 days.
결과적으로, 본 발명의 향청란 추출물은 패혈증에 의해 폭발적으로 증가된 염증성 사이토카인을 현저하게 감소시킬 뿐만 아니라, 패혈증으로 인한 사망율을 감소시켜 생존율을 크게 개선시킬 수 있음을 확인하였다.As a result, it was confirmed that the scented orchid extract of the present invention not only significantly reduces the inflammatory cytokines explosively increased by sepsis, but also significantly improves the survival rate by reducing the death rate due to sepsis.
<실험예 3> 향청란 추출물의 진통 효과<Experimental Example 3> Analgesic effect of scented orchid extract
본 발명의 향청란 추출물의 항통증 효과를 확인하기 위해 5주령 수컷 ICR 마우스에게 향청란 추출물 (200, 500 mg/kg)을 경구투여하였다. 향청란 경구투여 1시간 뒤, 5% 포르말린(formalin) 40 μL를 마우스의 우측 뒷 발바닥에 투여하여 통증을 유발하였다. 항통증 효과를 확인하기 위한 실험 절차는 도 12에 나타난 바와 같으며, 각 실험그룹당 처리 조건은 하기 표 2에 나타난 바와 같다. 구체적으로, 군 당 8마리씩 5분 간격으로 통증 관련 행동(Pain Related Behavior)을 40분 동안 관찰해 향청란 추출물의 항진통 효과 여부를 확인하였다. 통증 유발 직후, 0분~5분 (Phase Ⅰ)은 급성통증으로 물리적인 자극 (주사바늘)에 의한 염증성 통증으로 정의하였고, 20분~40분 (Phase Ⅱ)은 화학적 자극 (약물반응)에 의한 염증성 통증 및 신경과민화에 의한 신경병증성 통증으로 정의하였다. 각 군별 통증 관련 행동을 나타낸 시간(sec)을 측정한 결과는 표 2 및 도 13 내지 14에 나타내었다.To confirm the anti-pain effect of the Blue Orchid extract of the present invention, the Blue Orchid extract (200, 500 mg/kg) was orally administered to 5-week-old male ICR mice. After 1 hour of oral administration, 40 μL of 5% formalin was administered to the right hind sole of the mouse to induce pain. The experimental procedure for confirming the anti-pain effect is as shown in FIG. 12, and the treatment conditions for each experimental group are as shown in Table 2 below. Specifically, the pain-related behavior was observed for 40 minutes at 5-minute intervals by 8 rats per group to confirm the anti-analgesic effect of the scented orchid extract. Immediately after inducing pain, 0 to 5 minutes (Phase I) was defined as acute pain and inflammatory pain caused by physical stimulation (injection needle), and 20 to 40 minutes (Phase II) was defined as chemical stimulation (drug reaction). It was defined as inflammatory pain and neuropathic pain due to hypersensitivity. The results of measuring the time (sec) representing pain-related behavior for each group are shown in Table 2 and FIGS. 13 to 14.
도 13은 시간에 따른 통증 관련 행동 시간(sec)을 기록한 결과를 나타낸 그래프이다. 표 2는 각각 Phase Ⅰ과 Ⅱ에 해당하는 통증 관련 행동 시간을 합산하여 나타낸 표이고, 이를 도 14에 막대 그래프로 나타내었다. 본 발명의 향청란 추출물을 투여한 그룹에서 대조군 대비 통증 관련 행동 시간이 감소한 것으로 나타났고, 이러한 결과로부터 향청란 추출물이 염증성 통증 및 신경병증성 통증을 개선시킬 수 있음을 확인하였다. 13 is a graph showing the results of recording pain-related action time (sec) over time. Table 2 is a table showing the sum of pain-related action times corresponding to Phases I and II, respectively, and is shown in a bar graph in FIG. 14 . In the group administered with the Blue Orchid extract of the present invention, it was found that pain-related action time was reduced compared to the control group, and from these results, it was confirmed that the Blue Orchid extract could improve inflammatory pain and neuropathic pain.
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특히 청구범위에 나타나 있으며, 그와 동등한 범위내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.So far, the present invention has been looked at with respect to its preferred embodiments. Those of ordinary skill in the art to which the present invention pertains will understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative rather than a limiting point of view. The scope of the present invention is particularly indicated in the claims rather than the foregoing description, and all differences within the equivalent range should be construed as being included in the present invention.
Claims (13)
상기 향청란 추출물은 패혈증으로 인한 사망율 증가를 감소시키는 것을 특징으로 하는 약학적 조성물.According to claim 1,
The scented orchid extract is a pharmaceutical composition, characterized in that to reduce the increase in mortality due to sepsis.
상기 향청란 추출물은 패혈증으로 인한 염증성 사이토카인의 생성 또는 발현 증가를 억제하여 패혈증 예방 또는 치료 효과를 나타내는 것을 특징으로 하는 약학적 조성물.According to claim 1,
The perfumed orchid extract is a pharmaceutical composition, characterized in that by inhibiting the increase in the production or expression of inflammatory cytokines due to sepsis to exhibit the effect of preventing or treating sepsis.
상기 패혈증은 그람 음성균의 외막에 존재하는 지질다당류(Lipopolysaccharide)에 의해 유발되는 세균성 패혈증인 것을 특징으로 하는 약학적 조성물.According to claim 1,
The pharmaceutical composition, characterized in that the sepsis is bacterial sepsis caused by lipopolysaccharide present in the outer membrane of Gram-negative bacteria.
상기 통증은 염증성(inflammatory) 통증 또는 신경병증성(neuropathic) 통증인 것을 특징으로 하는 약학적 조성물.According to claim 1,
The pharmaceutical composition, characterized in that the pain is inflammatory pain or neuropathic pain.
상기 향청란 추출물은 향청란 잎 또는 전초로부터 추출되는 것을 특징으로 하는 약학적 조성물.According to claim 1,
The pharmaceutical composition, characterized in that the scented orchid extract is extracted from scented orchid leaves or outposts.
상기 향청란 추출물은 물, 탄소수 1 내지 탄소수 4의 알코올 또는 이들의 혼합용매로 추출하는 것을 특징으로 하는 약학적 조성물.According to claim 1,
The scented orchid extract is a pharmaceutical composition, characterized in that extracted with water, alcohol having 1 to 4 carbon atoms or a mixed solvent thereof.
상기 약학적 조성물은 경구용 제제, 주사용 제제 또는 외용제의 형태로 제형화되는 것을 특징으로 하는 약학적 조성물.According to claim 1,
The pharmaceutical composition is a pharmaceutical composition, characterized in that formulated in the form of oral preparations, injection preparations or external preparations.
상기 향청란 추출물은 패혈증으로 인한 사망율 증가를 감소시키는 것을 특징으로 하는 건강기능식품 조성물.According to claim 9,
The health functional food composition, characterized in that the fragrance blue orchid extract reduces the increase in mortality due to sepsis.
상기 향청란 추출물은 패혈증으로 인한 염증성 사이토카인의 생성 또는 발현 증가를 억제하여 패혈증 예방 또는 개선 효과를 나타내는 것을 특징으로 하는 건강기능식품 조성물.According to claim 9,
The health functional food composition, characterized in that the flavor blue orchid extract inhibits the production or expression increase of inflammatory cytokines due to sepsis to prevent or improve sepsis.
상기 통증은 염증성(inflammatory) 통증 또는 신경병증성(neuropathic) 통증인 것을 특징으로 하는 건강기능식품 조성물.According to claim 9,
The pain is a health functional food composition, characterized in that inflammatory (inflammatory) pain or neuropathic (neuropathic) pain.
상기 건강기능식품은 정제, 캡슐제, 환제, 액제, 분말 또는 과립 형태의 식품인 것을 특징으로 하는 건강기능식품 조성물.According to claim 9,
The health functional food is a health functional food composition, characterized in that the food in the form of tablets, capsules, pills, liquids, powders or granules.
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| KR1020200122009A KR20220039197A (en) | 2020-09-22 | 2020-09-22 | Composition for preventing or treating sepsis and pain comprising extracts of Dracocephalum moldavica |
| KR1020230101909A KR20230118790A (en) | 2020-09-22 | 2023-08-04 | Composition for preventing or treating sepsis and pain comprising extracts of Dracocephalum moldavica |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20160106341A (en) | 2015-03-02 | 2016-09-12 | 한림대학교 산학협력단 | Pharmaceutical composition comprising nicotinamide adenine dinucleotide as active ingredient for treatment or prevention of sepsis |
| KR20190020469A (en) | 2017-08-21 | 2019-03-04 | 주식회사 에이치앤케이바이오사이언스 | Compositions for preventing or treating pain comprising extracts of Lonicera caerulea |
-
2020
- 2020-09-22 KR KR1020200122009A patent/KR20220039197A/en not_active Application Discontinuation
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20160106341A (en) | 2015-03-02 | 2016-09-12 | 한림대학교 산학협력단 | Pharmaceutical composition comprising nicotinamide adenine dinucleotide as active ingredient for treatment or prevention of sepsis |
| KR20190020469A (en) | 2017-08-21 | 2019-03-04 | 주식회사 에이치앤케이바이오사이언스 | Compositions for preventing or treating pain comprising extracts of Lonicera caerulea |
Non-Patent Citations (1)
| Title |
|---|
| JV Roughan et al., European Journal of pain. 20(2); 231-240, 2016 |
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