KR20140088965A - Composition for Preventing, Treating or Improving of TRPV1-Mediated Disease comprising Extract from Lactuca raddeana as an Active Ingredient - Google Patents
Composition for Preventing, Treating or Improving of TRPV1-Mediated Disease comprising Extract from Lactuca raddeana as an Active Ingredient Download PDFInfo
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- KR20140088965A KR20140088965A KR1020120158100A KR20120158100A KR20140088965A KR 20140088965 A KR20140088965 A KR 20140088965A KR 1020120158100 A KR1020120158100 A KR 1020120158100A KR 20120158100 A KR20120158100 A KR 20120158100A KR 20140088965 A KR20140088965 A KR 20140088965A
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Abstract
Description
본 발명은 산씀바귀(Lactuca raddeana) 추출물을 유효성분으로 포함하는 TRPV1-매개 질환의 예방, 치료 또는 개선용 조성물에 관한 것이다.
The present invention relates to a process for producing Lactuca raddeana) it relates to the extract to a composition for the prevention, treatment or amelioration of TRPV1- mediated diseases comprising, as an active ingredient.
TRPV1(Transient receptor potential channel, Vanilloid subfamily member 1)은 열과 시각 미각 후각 촉각의 영역을 포함하는 비전압 양이온 개폐 채널(non voltage gated cation channel)로 이루어진 TRP 채널의 큰 과에 속한다. TRPV1은 상승작용을 통해 상호 작용하는 열, 양성자 및 내인성 물질에 의해 활성화 된다. 고추의 매운맛을 내는 주요성분인 캡사이신(capsaicin)은 TRPV1 수용체를 활성화함으로써 통증을 초래한다. TRPV1은 통증 및 온도를 감지하는 뉴런의 막에 존재하는데, 우리가 고추를 먹을 때 즉시 작열감을 느끼는 이유는 고추의 성분인 캡사이신이 TRPV1을 활성화시키기 때문이다. 캡사이신을 국소 또는 전신에 투여했을 때, 처음에는 강한 자극성을 보이다가 지속적인 진통작용을 나타낸다는 사실이 알려지면서 수많은 캡사이신 유도체들이 합성되었고, 진통제로서의 개발이 시도되었다. TRPV1 활성제는 통증치료뿐 아니라, 염증반응에도 관여한다고 알려져 있어, 자생식물 및 식품유래 TRPV1의 활성제의 연구는 다양한 질병 및 예방효과에 도움이 될 것이라 생각된다.
TRPV1 (Transient receptor potential channel, Vanilloid subfamily member 1) belongs to the large part of the TRP channel, which is composed of a non-voltage gated cation channel that includes the area of the sensory tactile sense of heat and visual taste. TRPV1 is activated by interacting heat, proton and endogenous substances through synergism. Capsaicin, a major component of hot pepper, causes pain by activating the TRPV1 receptor. TRPV1 is present in the membranes of neurons that sense pain and temperature. The reason we feel burning immediately when we eat peppers is because capsaicin, a component of pepper, activates TRPV1. A number of capsaicin derivatives have been synthesized and developed as analgesics, as the fact that capsaicin is administered topically or systemically indicates that it initially exhibits strong irritation and exhibits a persistent analgesic effect. Since TRPV1 activators are known to be involved not only in pain therapy but also in inflammatory responses, studies of activators of native and plant-derived TRPV1 may be helpful in a variety of diseases and preventive effects.
본 명세서 전체에 걸쳐 다수의 논문 및 특허문헌이 참조되고 그 인용이 표시되어 있다. 인용된 논문 및 특허문헌의 개시 내용은 그 전체로서 본 명세서에 참조로 삽입되어 본 발명이 속하는 기술 분야의 수준 및 본 발명의 내용이 보다 명확하게 설명된다.
Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.
본 발명자들은 통증과 관련된 TRPV1(Transient Receptor Potential channel, Vanilloid subfamily member 1)을 활성화시키는 천연물 소재를 개발하고자 노력하였다. 그 결과, 산씀바귀(Lactuca raddeana) 추출물이 hTRPV1을 활성화시킴으로써 TRPV1-매개 질환, 예를 들어 통증, 호흡기 질환 또는 하부 요로계 질환, 특히 통증을 완화시키는 진통제로서 효과가 우수함을 규명함으로써 본 발명을 완성하게 되었다.The present inventors have sought to develop a natural material for activating TRPV1 (Transient Receptor Potential channel, Vanilloid subfamily member 1) associated with pain. As a result, the present invention was completed by confirming that Lactuca raddeana extract is effective as an analgesic agent for relieving TRPV1-mediated diseases such as pain, respiratory diseases or lower urinary tract diseases, particularly pain, by activating hTRPV1 .
따라서, 본 발명의 목적은 TRPV1-매개 질환의 예방, 치료 또는 개선용 조성물을 제공하는 데 있다.It is therefore an object of the present invention to provide a composition for the prevention, treatment or amelioration of TRPV1-mediated diseases.
본 발명의 다른 목적은 TRPV1의 길항제 스크리닝 방법을 제공하는 데 있다.
Another object of the present invention is to provide a method for screening antagonists of TRPV1.
본 발명의 다른 목적 및 이점은 하기의 발명의 상세한 설명, 청구범위 및 도면에 의해 보다 명확하게 된다.
Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.
본 발명의 일 양태에 따르면, 본 발명은 산씀바귀(Lactuca raddeana) 추출물을 유효성분으로 포함하는 TRPV1(Transient Receptor Potential channel, Vanilloid subfamily member 1)-매개 질환의 예방, 치료 또는 개선용 조성물을 제공한다.
According to one aspect of the present invention, there is provided a composition for preventing, treating or improving TRPV1 (Transient Receptor Potential channel, vanilloid subfamily member 1) -mediated disease comprising Lactuca raddeana extract as an active ingredient .
본 발명자들은 통증과 관련된 TRPV1(Transient Receptor Potential channel, Vanilloid subfamily member 1)을 활성화시키는 천연물 소재를 개발하고자 노력하였다. 그 결과, 산씀바귀(Lactuca raddeana) 추출물이 hTRPV1을 활성화시킴으로써 TRPV1-매개 질환, 예를 들어 통증, 호흡기 질환 또는 하부 요로계 질환, 특히 통증을 완화시키는 진통제로서 효과가 우수함을 규명하였다.
The present inventors have sought to develop a natural material for activating TRPV1 (Transient Receptor Potential channel, Vanilloid subfamily member 1) associated with pain. As a result, Lactuca raddeana extract was found to be effective as an analgesic agent for relieving TRPV1-mediated diseases such as pain, respiratory diseases or lower urinary tract diseases, particularly pain, by activating hTRPV1.
본 발명의 조성물에서 이용되는 산씀바귀 추출물은 산씀바귀에 추출용매를 처리하여 수득하는 경우에는, 다양한 추출용매가 이용될 수 있다. 본 발명의 일 구현예에 따르면, 상기 추출용매로서 극성 용매 또는 비극성 용매를 이용할 수 있다. 극성 용매로서 적합한 것은, (i) 물, (ii) 알코올(본 발명의 일 구현예에 따르면, 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올, 노말-부탄올, 1-펜탄올, 2-부톡시에탄올 또는 에틸렌글리콜), (iii) 아세트산, (iv) DMFO(dimethyl-formamide) 및 (v) DMSO(dimethyl sulfoxide)를 포함한다. 비극성 용매로서 적합한 것은, 아세톤, 아세토나이트릴, 에틸 아세테이트, 메틸 아세테이트, 플루오로알칸, 펜탄, 헥산, 2,2,4-트리메틸펜탄, 데칸, 사이클로헥산, 사이클로펜탄, 디이소부틸렌, 1-펜텐, 1-클로로부탄, 1-클로로펜탄, o-자일렌, 디이소프로필 에테르, 2-클로로프로판, 톨루엔, 1-클로로프로판, 클로로벤젠, 벤젠, 디에틸 에테르, 디에틸 설파이드, 클로로포름, 디클로로메탄, 1,2-디클로로에탄, 어닐린, 디에틸아민, 에테르, 사염화탄소 및 THF를 포함한다.When the acid scavenger extract used in the composition of the present invention is obtained by treating the acid scavenger with an extraction solvent, various extraction solvents can be used. According to an embodiment of the present invention, a polar solvent or a non-polar solvent may be used as the extraction solvent. Suitable polar solvents are (i) water, (ii) alcohol (according to one embodiment of the invention, methanol, ethanol, propanol, butanol, n-propanol, iso- 2-butoxyethanol or ethylene glycol), (iii) acetic acid, (iv) dimethylformamide (DMFO) and (v) dimethyl sulfoxide (DMSO). Suitable nonpolar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1- But are not limited to, pentane, 1-chlorobutane, 1-chloropentane, o -xylene, diisopropyl ether, 2- chloropropane, toluene, 1- chloropropane, chlorobenzene, benzene, diethyl ether, diethylsulfide, Methane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride, and THF.
본 발명의 일 구현예에 따르면, 본 발명에서 이용되는 추출용매는 (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올 (메탄올, 에탄올, 프로판올, 부탄올 등), (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르를 포함한다. 본 발명의 일 구현예에 따르면, 본 발명의 추출물은 물, 에탄올 또는 이의 조합을 산씀바귀에 처리하여 수득한 것이다.According to an embodiment of the present invention, the extraction solvent used in the present invention may be selected from the group consisting of (a) water, (b) an anhydrous or hydrated lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, (E) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane, and (j) Diethyl ether. According to one embodiment of the present invention, the extract of the present invention is obtained by treating water, ethanol or a combination thereof with an acid scavenger.
본 발명의 일 구현예에 따르면, 본 발명의 산씀바귀 추출물은 에탄올로 추출한 산씀바귀 추출물이다.According to one embodiment of the present invention, the acid scavenger extract of the present invention is an acid scavenger extract extracted with ethanol.
본 명세서에서 사용되는 용어 ‘추출물’은 상술한 바와 같이 당업계에서 조추출물(crude extract)로 통용되는 의미를 갖지만, 광의적으로는 추출물을 추가적으로 분획(fractionation)한 분획물도 포함한다. 즉, 산씀바귀 추출물은 상술한 추출용매를 이용하여 얻은 것뿐만 아니라, 여기에 정제과정을 추가적으로 적용하여 얻은 것도 포함한다. 예컨대, 상기 추출물을 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 얻은 분획, 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 산씀바귀 추출물에 포함되는 것이다.As used herein, the term " extract " means that it is used in the art as a crude extract as described above, but broadly includes fractions obtained by further fractionating the extract. That is to say, the extract of Acarina is not only obtained by using the above-mentioned extraction solvent but also by additionally applying a purification process thereto. For example, a fraction obtained by passing the above extract through an ultrafiltration membrane having a constant molecular weight cut-off value, and a separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity) The fraction obtained by the purification method is also included in the acid scavenger extract of the present invention.
본 발명에서 이용되는 산씀바귀 추출물은 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.The acid scavenger extract used in the present invention can be prepared into a powder state by an additional process such as vacuum distillation and freeze drying or spray drying.
본 명세서에서 용어 ‘유효성분으로 포함하는’이란 하기의 산씀바귀 추출물의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 본 발명은 천연식물재료인 산씀바귀로부터 추출한 조성물로서 과량 투여하여도 인체에 부작용이 없으므로 산씀바귀 추출물이 본 발명의 조성물에 포함된 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.
As used herein, the term " comprising as an active ingredient " is meant to include an amount sufficient to achieve efficacy or activity of the following acid scavenger extract. The present invention is a composition extracted from a natural plant material, which is a natural plant material. Since the plant extract does not adversely affect the human body even when it is administered in an excessive amount, the quantitative upper limit of the composition containing the extract of the plant extract can be selected by a person skilled in the art within a suitable range.
본 발명의 조성물은 TRPV1-매개 질환의 예방, 치료 또는 개선용 조성물이다.The composition of the present invention is a composition for preventing, treating or ameliorating a TRPV1-mediated disease.
상기 TRPV1-매개 질환은 통증(US 7943166, US20070105920), 호흡기 질환(US20120225808, WO06038070) 또는 하부 요로계 질환(US20100261911, US20110065764)이고, 상기 통증은 급성 또는 만성 통증 장애, 급성 또는 만성 신경성 통증, 급성 또는 만성 염증성 통증을 포함한다.Wherein said TRPV1-mediated disease is selected from the group consisting of pain (US 7943166, US20070105920), respiratory disease (US20120225808, WO06038070) or lower urinary tract disease (US20100261911, US20110065764), said acute or chronic pain disorder, acute or chronic neuropathic pain, Inflammatory pain.
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 TRPV1를 활성화시킨다. 상기 TRPV1은 통증과 온도를 감지하는 뉴런의 막에 존재하는 통각수용체이다. TRPV1이 활성화되면 초기에는 자극성을 보이다가 지속적인 진통작용을 나타낸다.According to one embodiment of the present invention, the composition of the present invention activates TRPV1. The TRPV1 is a pain receptor present in the membrane of a neuron that senses pain and temperature. When TRPV1 is activated, it exhibits irritation in the early stages and sustained analgesic activity.
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 세포 내 칼슘 이온의 유입량을 증가시킨다. 상기 TRPV1은 리간드가 결합하면 통로가 열리면서 세포 밖의 나트륨 이온 및 칼슘 이온이 세포 내로 유입되게 된다. 그 결과, 신경세포 내부의 전위가 바뀌면서 세포 막 전위를 증가시키고 전기 신호가 축색돌기를 타고 척수를 거쳐 대뇌로 전달되어 통증과 열을 느끼게 된다.According to one embodiment of the invention, the composition of the present invention increases the inflow of intracellular calcium ions. When the ligand binds to TRPV1, the passage opens and sodium ions and calcium ions out of the cells are introduced into the cells. As a result, the electric potential inside the nerve cell is changed and the cell membrane potential is increased, and the electric signal is transmitted to the cerebrum through the axons and the spinal cord to feel pain and heat.
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 PKC-α(Protein Kinase C-alpha)를 인산화시킨다. 본 발명의 산씀바귀 추출물은 상기 PKC-α의 활성화 시키고 활성화된 PKC-α는 TRPV1을 활성화 시킨다.
According to one embodiment of the present invention, the composition phosphorylates PKC-alpha (Protein Kinase C-alpha). The acid scavenger extract of the present invention activates PKC-alpha and activates PKC-alpha activates TRPV1.
본 발명의 조성물은 식품 조성물, 기능성 식품 조성물 또는 약제학적 조성물이다.The composition of the present invention is a food composition, a functional food composition or a pharmaceutical composition.
본 발명의 조성물은 식품 조성물로 제공될 수 있다. 본 발명의 산씀바귀 추출물을 유효성분으로 포함하는 TRPV1-매개 질환의 예방, 치료 또는 개선용 조성물이 식품 조성물로 제조되는 경우, 유효성분으로서 산씀바귀 추출물뿐 만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제로 제조되는 경우에는 본 발명의 산씀바귀 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 두충 추출액, 대추 추출액, 감초 추출액 등을 추가로 포함시킬 수 있다.
The composition of the present invention can be provided as a food composition. When the composition for preventing, treating or ameliorating a TRPV1-mediated disease comprising an acid scavenger extract of the present invention as an active ingredient is prepared from a food composition, not only an acid scavenger extract as an active ingredient, but also an acid scavenger extract And includes, for example, proteins, carbohydrates, fats, nutrients, flavoring agents, and flavoring agents. Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavorings such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavorings (saccharine, aspartame, etc.) can be used as flavorings. For example, when the food composition of the present invention is prepared as a drink, it may further contain citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, mulberry extract, jujube extract, licorice extract, .
본 발명의 산씀바귀 추출물을 유효성분으로 포함하는 TRPV1-매개 질환의 예방, 치료 또는 개선용 조성물로 제조될 수 있다. 본 발명의 조성물이 기능성 식품 조성물로 제조되는 경우, 식품 제조 시 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소 및 조미제를 포함한다. 예컨대, 드링크제로 제조되는 경우에는 유효성분으로서 산씀바귀 추출물 이외에 향미제 또는 천연 탄수화물을 추가 성분으로 포함시킬 수 있다. 예를 들어, 천연 탄수화물은 모노사카라이드(예컨대, 글루코오스, 프럭토오스 등); 디사카라이드(예컨대, 말토스, 수크로오스 등); 올리고당; 폴리사카라이드(예컨대, 덱스트린, 시클로덱스트린 등); 및 당알코올(예컨대, 자일리톨, 소르비톨, 에리쓰리톨 등)을 포함한다. 향미제로서 천연 향미제(예컨대, 타우마린, 스테비아 추출물 등) 및 합성 향미제(예컨대, 사카린, 아스파르탐 등)을 이용할 수 있다.
The composition of the present invention can be prepared from a composition for preventing, treating or ameliorating a TRPV1-mediated disease comprising an acid scavenger extract as an active ingredient. When the composition of the present invention is prepared with a functional food composition, it includes components that are conventionally added in food production, and includes, for example, proteins, carbohydrates, fats, nutrients, and seasonings. For example, in the case of being made with a drink, as an active ingredient, flavorings or natural carbohydrates may be added as an additional ingredient in addition to an extract of Acanthopanax senticosus. For example, natural carbohydrates include monosaccharides (e.g., glucose, fructose, etc.); Disaccharides (e.g., maltose, sucrose, etc.); oligosaccharide; Polysaccharides (e.g., dextrin, cyclodextrin and the like); And sugar alcohols (e.g., xylitol, sorbitol, erythritol, etc.). Natural flavoring agents (e.g., tau marin, stevia extract, etc.) and synthetic flavoring agents (e.g., saccharin, aspartame, etc.) may be used as flavorings.
본 발명의 산씀바귀 추출물을 유효성분으로 포함하는 TRPV1-매개 질환의 예방, 치료 또는 개선용 조성물은 약제학적 조성물로 제조될 수 있다. 본 발명의 조성물은 (a) 상술한 본 발명의 산씀바귀 추출물의 약제학적 유효량; 및 (b) 약제학적으로 허용되는 담체를 포함하는 약제학적 조성물이다. 본 명세서에서 용어 “약제학적 유효량”은 상술한 산씀바귀 추출물의 효능 또는 활성을 달성하는 데 충분한 양을 의미한다.The composition for the prevention, treatment or amelioration of a TRPV1-mediated disease comprising the acid scavenger extract of the present invention as an active ingredient can be prepared from a pharmaceutical composition. The composition of the present invention comprises (a) a pharmaceutically effective amount of the above-mentioned acid scarlet extract of the present invention; And (b) a pharmaceutically acceptable carrier. As used herein, the term " pharmaceutically effective amount " means an amount sufficient to achieve efficacy or activity of the above-mentioned acid scavenger extract.
본 발명의 조성물이 약제학적 조성물로 제조되는 경우, 본 발명의 약제학적 조성물은 약제학적으로 허용되는 담체를 포함한다. 본 발명의 약제학적 조성물에 포함되는 약제학적으로 허용되는 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약제학적 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. 적합한 약제학적으로 허용되는 담체 및 제제는 Remington's Pharmaceutical Sciences (19th ed., 1995)에 상세히 기재되어 있다.When the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the present invention and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).
본 발명의 약제학적 조성물은 경구 또는 비경구 투여할 수 있다.The pharmaceutical composition of the present invention can be administered orally or parenterally.
본 발명의 약제학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다. 본 발명의 약제학적 조성물의 일반적인 투여량은 성인 기준으로 0.001-100 ㎎/kg 범위 내이다.The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . Typical dosages of the pharmaceutical compositions of this invention are in the range of 0.001-100 mg / kg on an adult basis.
본 발명의 약제학적 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액, 시럽제 또는 유화액 형태이거나 엑스제, 산제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.
The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of excipients, powders, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
본 발명의 다른 양태에 따르면, 다음의 단계를 포함하는 TRPV1(Transient Receptor Potential channel, Vanilloid subfamily member 1)의 길항제 스크리닝 방법을 제공한다:According to another aspect of the present invention there is provided a method for screening antagonists of TRIPV1 (Transient Receptor Potential channel, Vanilloid subfamily member 1) comprising the steps of:
(a) TRPV1 단백질을 포함하는 세포에 상기 제 1 항 내지 제 7 항 중 어느 한 항의 조성물 및 분석하고자 하는 시료를 접촉시키는 단계; 및(a) contacting a cell containing a TRPV1 protein with the composition of any one of
(b) 상기 조성물을 단독처리한 세포와 비교하여 상기 TRPV1의 활성이 감소-조절 되는 것으로 측정되는 경우에는 상기 시료는 TRPV1 길항제로 판정된다.
(b) the sample is determined to be a TRPV1 antagonist if it is determined that the activity of said TRPV1 is reduced-regulated relative to cells that have been treated with said composition alone.
본 발명의 방법에 따르면, 우선 TRPV1 단백질을 포함하는 세포에 본 발명의 조성물 및 분석하고자 하는 시료를 접촉시킨다. 상기 TRPV1 단백질을 포함하는 세포는 TRPV1이 형질전환되어 TRPV1이 과발현되는 세포이다. 본 발명의 스크리닝 방법을 언급하면서 사용되는 용어 “시료”는 TRPV1 단백질의 활성에 영향을 미치는 지 여부를 검사하기 위하여 스크리닝에서 이용되는 미지의 물질을 의미한다. 상기 시료는 화학물질, 뉴클레오타이드, 안티센스-RNA, siRNA(small interference RNA) 및 천연물 추출물을 포함하나, 이에 한정되는 것은 아니다.According to the method of the present invention, first, the composition of the present invention and a sample to be analyzed are brought into contact with cells containing the TRPV1 protein. The TRPV1 protein-containing cell is a cell in which TRPV1 is transformed and TRPV1 is overexpressed. The term " sample " used in reference to the screening method of the present invention means an unknown substance used in screening to check whether it affects the activity of the TRPV1 protein. Such samples include, but are not limited to, chemicals, nucleotides, antisense-RNA, siRNA (small interference RNA) and natural extracts.
이어, 시료가 처리된 세포에서 TRPV1 단백질의 활성을 측정한다. 측정 결과, 본 발명의 조성물을 처리한 대조군과 비교하여 본 발명의 조성물 및 시료를 처리한 실험군에서 TRPV1의 활성이 감소-조절되는 것이 측정되면, 상기 시료는 TRPV1 길항제로 판정될 수 있다.
Then, the activity of the TRPV1 protein is measured in the sample-treated cells. As a result of the measurement, when it is determined that the activity of TRPV1 is reduced-regulated in the experimental group treated with the composition of the present invention and the sample as compared with the control group treated with the composition of the present invention, the sample can be determined as a TRPV1 antagonist.
본 발명의 특징 및 이점을 요약하면 다음과 같다: The features and advantages of the present invention are summarized as follows:
(a) 본 발명은 산씀바귀 추출물을 유효성분으로 포함하는 TRPV1-매개 질환의 예방, 치료 또는 개선용 조성물 및 TRPV1의 길항제 스크리닝 방법을 제공한다.(a) The present invention provides a composition for the prevention, treatment or amelioration of a TRPV1-mediated disease comprising an acid scavenger extract as an active ingredient and a method for screening antagonist of TRPV1.
(b) 본 발명의 조성물은 천연 식물재료인 산씀바귀로부터 추출한 조성물로써 인체에 부작용이 없는 조성물을 제공할 수 있다.(b) The composition of the present invention is a composition extracted from a natural plant material, which is a natural plant material, and can provide a composition having no side effects on the human body.
(c) 본 발명의 조성물은 통증 및 염증의 예방, 치료 또는 개선 효과를 제공한다.
(c) The composition of the present invention provides preventive, therapeutic or ameliorative effects of pain and inflammation.
도 1은 TRPV1 유전자 를 삽입한 pcDNA-rTRPV1 및 GFP를 형질전환한 HEK293(Human Embryonic Kidney 293) 세포의 GFP(Green Fluorescence Protein) 발현을 확인한 형광현미경 사진을 보여준다.
도 2는 TRPV1 유전자 를 삽입한 pcDNA-rTRPV1 및 GFP를 형질전환한 HEK293(Human Embryonic Kidney 293) 세포의 TRPV1 발현을 확인한 웨스턴 블럿 결과를 나타낸다.
도 3은 TRPV1-발현 HEK293 세포의 칼슘 유입에 대한 산씀바귀 추출물의 영향을 나타낸 결과이다.
도 4는 TRPV1-발현 HEK293 세포의 산씀바귀 추출물의 농도 반응 곡선을 나타낸다.
도 5는 CPZ(Capsazepin) 및 SB-366791의 산씀바귀 추출물-유도 TRPV1 활성의 억제에 대한 영향을 나타낸다.
도 6a 및 도 6b는 TRPV1-발현 세포에서 막 전위에 대한 산씀바귀 추출물의 영향을 나타낸다. 도 6a는 시간에 따른 곡선을 나타내고, 도 6b는 평균 △RFU(Relative Fluorescence Units) 값을 나타낸다.
도 7은 TRPV1-발현 세포에서 PKC-α의 인산화에 대한 산씀바귀 추출물에 영향을 나타낸다.
도 8a 및 도 8b는 PKC-α 억제제에 의한 산씀바귀 추출물-유도 Ca2+ 유입을 확인한 결과이다. 도 8a는 시간에 따른 곡선을 나타내고, 도 6b는 도 6b는 평균 △RFU(Relative Fluorescence Units) 값을 나타낸다.FIG. 1 shows fluorescent micrographs of GFP (Green Fluorescence Protein) expression of pcDNA-rTRPV1 transfected with TRPV1 gene and HEK293 (Human Embryonic Kidney 293) transformed with GFP.
Figure 2 shows Western blot results confirming TRPV1 expression of pcDNA-rTRPV1 transfected with TRPV1 gene and HEK293 (Human Embryonic Kidney 293) transfected with GFP.
Figure 3 shows the effect of acid extract on the calcium influx of TRPV1-expressing HEK293 cells.
Figure 4 shows the concentration response curves of Acanthopanax senticosus extract of TRPV1-expressing HEK293 cells.
Figure 5 shows the effect of CPZ (Capsazepin) and SB-366791 on the inhibition of acid sucker extract-induced TRPV1 activity.
Figures 6a and 6b show the effect of Acanthopanax senticosus extract on membrane potential in TRPV1-expressing cells. FIG. 6A shows a curve over time, and FIG. 6B shows an average relative fluorescence units (RFU) value.
Figure 7 shows the effect of acid scavenger extract on phosphorylation of PKC-a in TRPV1-expressing cells.
Figures 8a and 8b show the results of ascites extract-induced Ca2 + influx by PKC-alpha inhibitor. FIG. 8A shows a curve with time, and FIG. 6B shows an average relative fluorescence units (RFU) value.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .
실시예 1: 통각수용체 일시발현 세포주에 작용하는 식물 및 식품유래 소재 스크리닝Example 1: Screening of plants and food-derived materials acting on temporal receptors transiently expressing cell lines
식물 및 식품유래 추출물의 시료확보Samples of plant and food-derived extracts
자생식물 및 식품 유래 매운맛 또는 자극적인 맛을 지닌 수종의 식물 및 식품 후보 종을 문헌검색 및 사전조사로 확인하여 에탄올 추출물과 물 추출물을 확보하였고, 에탄올 추출물을 실험에 사용하였다. 가장 효능이 좋았던 식품유래 추출물은 표 1과 같다.Ethanol extracts and water extracts were obtained, and the ethanol extracts were used for the experiments. The extracts of the plants and food candidates of spicy or irritating taste derived from native plants and foods were confirmed by literature search and preliminary investigation. Table 1 shows the most effective food-borne extracts.
TRPV1 일시발현 세포주 배양TRPV1 transient expression cell line culture
통각 수용체의 활성제를 스크리닝을 하기위하여, TRPV1 수용체 일시발현 세포주를 확보하였다. HEK293(Human Embryonic Kidney 293) 세포는 트랜스펙션(transfection)이 잘되는 세포주로서 타겟 단백질 과발현(overexpression) 목적으로 흔히 사용된다. HEK293 세포주에 클로닝한 랫트 TRPV1 유전자를 트랜스펙션 기법을 이용하여 과발현 시켰다(Direct activation of Transient Receptor Potential Vanilloid 1(TRPV1) by Diacylglycerol (DAG), Dong Ho Woo 외, Moleular pain, 2008 (4); 42). 트랜스펙션의 효율이 실험에 중요한 역할을 하기 때문에 GFP(Green Fluorescence Protein)가 표지된 유전자를 공동-트랜스펙션하여 트랜스펙션 효율을 측정하고, TRPV1의 과발현 정도를 측정하기 위해 웨스턴 블럿 기법으로 TRPV1 수용체(VR1)의 발현량을 확인하였다(도 1). pcDNA-rTRPV1(Direct activation of Transient Receptor Potential Vanilloid 1(TRPV1) by Diacylglycerol (DAG), Dong Ho Woo 외, Moleular pain, 2008 (4); 42)을 주입한 HEK293의 세포를 24시간-48시간 내에 단백질을 추출하여 항-VR1 항체(Santa curz, Biotechnology, CA, USA) 발현량을 측정한 결과, TRPV1의 발현이 25배 정도 증가된 것을 확인하였고, 이 세포를 이용하여 실험에 사용하였다(도 2).
In order to screen the activator of the pain receptor, a transiently expressing TRPV1 receptor cell line was obtained. HEK293 (Human Embryonic Kidney 293) cells are well-transfected cell lines and are often used for overexpression of target proteins. The rat TRPV1 gene cloned in the HEK293 cell line was overexpressed using transfection technique (Direct activation of transient receptor potent vanilloid 1 (TRPV1) by diacylglycerol (DAG), Dong Ho Woo et al., Molecular pain, 2008 (4) ). Since transfection efficiency plays an important role in the experiment, the transfection efficiency was measured by co-transfected GFP (Green Fluorescence Protein) -labeled gene, and Western blot technique was used to measure TRPV1 overexpression The expression level of the TRPV1 receptor (VR1) was confirmed (Fig. 1). HEK293 cells injected with pcDNA-rTRPV1 (TRPV1) by Diacylglycerol (DAG), Dong Ho Woo et al., Molecular pain, 2008 (4) VR1 antibody (Santa curz, Biotechnology, CA, USA), and the expression of TRPV1 was increased by about 25-fold. The cells were used for the experiment (FIG. 2) .
후보물질 칼슘유입량 측정 및 스크리닝Candidate Calcium Inflow Measurement and Screening
TRPV1은 고전적으로 열 민감성, 리간드 관문성, 비선택적 양이온채널로 분류되며, 감각뉴런에서 통증자극을 통합하는 것으로 알려져 있다. TRPV1은 통증 및 온도를 감지하는 뉴런의 막에 존재하는데, 우리가 고추를 먹을 때 작열감을 느끼는 이유는 고추의 성분인 캡사이신이 통증뉴런의 TRPV1을 활성화시키기 때문이다. 온도가 42℃가 넘거나 캡사이신과 같은 물질이 결합하면 통로가 열리면서 세포 밖의 나트륨 이온(Na2 +)과 칼슘 이온(Ca2 +)이 세포 안으로 들어오게 된다. 그 결과, 신경세포내부의 전위가 바뀌면서 막 전위가 변화되어 전기신호가 축색돌기를 타고 척수를 거쳐 대뇌로 전달되어 통증과 열을 느끼게 된다.TRPV1 is classically classified as a heat-sensitive, ligand-gated, non-selective cation channel and is known to integrate pain stimulation in sensory neurons. TRPV1 is present in the membranes of neurons that sense pain and temperature. The reason we feel a burning sensation when we eat peppers is because capsaicin, a component of pepper, activates TRPV1 in pain neurons. When the temperature is 42 ℃ over or material combination, such as capsaicin are let in, which opens the passage of sodium ions out of the cell (Na 2 +) and calcium ions (Ca 2 +) cell. As a result, the potential inside the nerve cell is changed and the membrane potential changes, so that the electric signal is transmitted to the cerebrum through the axons and the spinal cord to feel pain and heat.
이러한 원리로, TRPV1에 대한 길항제 및 작용제의 연구는 칼슘유입으로 스크리닝 될 수 있다. 본 연구에서는 TRPV1의 활성을 유발시키거나, 길항 작용을 하는 물질을 찾는 목적으로 우선 식물 및 식품유래 후보물질을 선발하여, 칼슘의 유입을 측정하였다.With this principle, studies of antagonists and agonists against TRPV1 can be screened with calcium influx. In this study, for the purpose of inducing TRPV1 activity or antagonistic activity, candidate substances of plant and food were selected and calcium influx was measured.
TRPV1의 유전자를 HEK293 세포에 주입한 후, 24-48시간 후에 TRPV1의 발현을 확인하고, 이 세포를 96웰 플레이트에 8×105 세포/웰로 분주한 후, 24시간 배양하였다. 캡사이신(양성 대조군) 또는 HL 추출물(실험군) 10 ㎍/㎖를 준비하여 작용제 및 길항제의 스크리닝에 사용하였다. 배양한지 24시간 후에 Ca2 +4 염색시약(Molecular devices, CA, USA)을 처리하여 1시간 동안 배양한 후, FlexStation 3 Microplaste Reader(Molecular Devices, 미국)로 칼슘유입량을 측정하였다. 그 결과 HL 종의 추출물에서 RFU(Relative Fluorescence Units)가 100으로 측정되었고, 이는 음성대조군과 비교하여 3.3배 이상의 Ca2 + 유입량을 보여 유의적으로 증가했음을 확인하였다(표 2). 이때 양성 대조군으로 사용된 캡사이신은 평균 200을 넘는 RFU 수치를 보였다.After the TRPV1 gene was injected into HEK293 cells, the expression of TRPV1 was confirmed after 24-48 hours. The cells were divided into 8 × 10 5 cells / well in a 96-well plate and cultured for 24 hours. Capsaicin (positive control) or HL extract (experimental group) 10 / / ml was prepared and used for screening of agonists and antagonists. Culture after 24
음성 대조군으로는 Ca2 + 이 첨가되지 않은 HBSS(Hank's balanced salt solution )에 0.001% DMSO를 첨가하여 사용하였다. The negative control was used as the addition of 0.001% DMSO in the non-addition of Ca 2 + HBSS (Hank's balanced salt solution) .
(대조군 상대값)Fold value of calcium ion influx
(Control relative value)
칼슘이온유입량의 폴드값 = 시료처리군의 칼슘유입량 / 대조군의 칼슘유입량
Fold value of calcium ion inflow = Calcium inflow of sample treatment group / Calcium inflow of control group
도출된 Derived HLHL 추출물의 시간별 및 농도별 By time and concentration of extract CaCa 22 ++ 유입량 측정 Inflow measurement
HL 추출물 처리 후, Ca2 +4 염료를 이용하여 시간별 및 농도별 Ca2 + 유입량을 ELISA(Enzyme-linked Immunosorbent Assay) 방법으로 측정하였다. 추출물의 농도에 따른 영향을 비교하기 위해 캡사이신도 동일한 농도(㎍/㎖)로 처리하였다. 1 ㎍/㎖ 캡사이신을 처리한 실험군에서는 처리 후 12초부터 칼슘유입량이 상승되어 120초까지 지속되었고, TRPV1 특이 억제제인 CPZ(capsazepin) 10 μM을 동시에 처리한 경우에, 캡사이신만 처리했을 때보다 칼슘유입량이 감소된 결과를 얻을 수 있었다. HL 추출물을 12초에 10 ㎍/㎖을 처리한 결과, 급속히 증가된 칼슘유입량은 캡사이신과 같이 120초까지 지속되었다. CPZ 10 μM을 동시에 처리하였을 때는, 음성대조군보다는 증가하였지만, HL 추출물에 의해 증가된 칼슘유입량처럼 증가되지 않음을 확인하였다(도 3). 이는 HL 추출물에 의한 칼슘유입량의 증가가 TRPV1 특이적일 가능성을 시사한다.HL extract after treatment, by using a
특히 캡사이신의 EC50(0.0059 ㎍/㎖)과 비교하였을 때, HL 추출물은 13.14 ㎍/㎖로 높은 EC50를 보였다.
Especially, when compared with the EC 50 (0.0059 ㎍ / ㎖) of capsaicin, the HL extract showed an EC 50 as high as 13.14 ㎍ / ㎖.
실시예2Example 2 : : HLHL 소재의 Of material 통각수용체일시발현세포주에To the temporal receptors transiently expressing cell line 작용제로서의 평가 및 기전연구 Evaluation and Mechanism of Agents
TRPV1의 활성화 기전은 두 가지 가설이 있다. 첫 번째 기전으로는 물질에 의해 세포내 신호전달 경로의 활성화에 의한 기전이며, 두 번째 기전으로는 물질이직접적으로 TRPV1을 활성화 하는 기전이다. 첫 번째 기전의 가능성을 검증하기 위하여 HL 관련 신호전달계를 차단한 후, HL 추출물과 캡사이신에 대한 반응을 관찰하였다. 자극에 반응하여 통로가 열리면 그곳을 통하여 여러 양이온들이 움직이게 되는데 세포막은 그 전위가 음성이기 때문에 세포 안으로 들어가는 양이온의 흐름이 나오는 흐름보다 크게 된다. 이에 따라 막전위는 탈분극이 일어나고 이러한 현상이 커지게 되어 전압의존성 이온통로들이 열리고 활동전위가 발행한다. HL 추출물이 막 전위의 변화를 일으키는지 확인하였다. 캡사이신과 같은 다양한 리간드, 산, 그리고 생리학적 자극, 단백질 키나제 C에 의한 TRPV1을 인산화 시키는 물질 등이 TRPV1의 활성제로 알려져 있다. Bradkinin은 PKC-α 의존 경로를 통해 VR1의 활성을 증가시킨다고 보고 되어져있다. 본 연구에서는, PKC-α를 활성화 시키는 물질 또한, TRPV1를 활성화 시킬 수 있다고 생각하고, 그 기전을 확인해 보고자 하였다.
Activation of TRPV1 has two hypotheses. The first mechanism is activation of the intracellular signaling pathway by the substance, and the second mechanism is that the substance directly activates TRPV1. To test the possibility of the first mechanism, HL-related signal transduction was blocked and the response to HL extract and capsaicin was observed. When the channel is opened in response to the stimulus, a number of positive ions move through the cell. The cell membrane becomes larger than the flow of the cation ions flowing into the cell because the potential is negative. As a result, the membrane potential is depolarized and this phenomenon becomes large, so that voltage dependent ion channels are opened and action potentials are issued. HL extracts induced changes in membrane potential. Various ligands, acids and physiological stimulants such as capsaicin, and substances that phosphorylate TRPV1 by protein kinase C are known as activators of TRPV1. Bradkinin has been reported to increase the activity of VR1 through a PKC-a dependent pathway. In this study, PKC-α activating substance was also thought to activate TRPV1 and its mechanism was confirmed.
HLHL 추출물의 막 전위 변화 측정 Measurement of membrane potential change of extract
HL 추출물의 TRPV1 활성화 기전을 확인하기 위하여 막전위변화를 측정하였다. TRPV1-발현 세포를 5×106 세포/웰로 분주하여 배양한 뒤 24시간 후에 막 전위 키트(FLIPR membrane potential Assay kit Flurometric imaging Plate system, 미국)를 이용하여 세포막 전위차를 확인하였다. 막 전위 키트는 세포질 막을 통과하여 세포막전위차가 일어났을 경우 염료가 많이 세포 안으로 들어가기 때문에, 형광 신호가 증가된다. HL 추출물을 12초에 처리하였을 때, 형광 신호가 증가되는 것을 확인하였고, 이는 CPZ를 10 μM로 동시 처리하였을 때는 증가하는 경향을 나타내지 않았다. 이는 HL 추출물이 막 전위를 증가시킨다고 할 수 있다.
The membrane potential change was measured to determine the TRPV1 activation mechanism of HL extract. TRPV1-expressing cells were cultured at 5 × 10 6 cells / well. After 24 hours, the cell membrane potential difference was confirmed using a FLIP membrane potential assay kit (Fluorometric imaging plate system, USA). When the membrane potential kits pass through the cytoplasmic membrane and the cell membrane potential difference occurs, the fluorescence signal increases because the dye enters the cell much more. When the HL extract was treated at 12 seconds, the fluorescence signal was increased and it did not show an increasing tendency when CPZ was treated at 10 μM. This suggests that the HL extract increases the membrane potential.
HLHL 추출물의 Extract PKCPKC -α의 인산화 변화 측정-phosphorylation change measurement
HL 추출물이 PKC-α를 인산화 시키는지 확인하기 위하여, TRPV1-발현 세포에 HL 추출물 10 ㎍/㎖을 처리한 후, 단백질을 추출하여 웨스턴 블럿으로 PKC-α 인산화를 확인하였다. HL 추출물을 처리한 군에서는 PKC-α 인산화가 3배 이상 증가하였다. 이는 HL 추출물이 PKC-α를 활성화 시키고 활성화된 PKC-α는 TRPV1 채널을 활성화 시킨다고 생각된다.
In order to confirm that the HL extract phosphorylates PKC-α, TRPV1-expressing cells were treated with 10 μg / ml of HL extract, and proteins were extracted and PKC-α phosphorylation was confirmed by Western blotting. In the HL extract-treated group, PKC-α phosphorylation was more than 3-fold increased. It is thought that HL extract activates PKC-α and activated PKC-α activates TRPV1 channel.
PKCPKC -α 억제제에 의한 -α inhibitor HLHL 로 유도된 Induced CaCa 22 + + 유입 억제 Inflow inhibition
HL 추출물의 PKC-α영향을 확인하기 위하여, PKC-α의 억제제를 처리하고 Ca2 + 유입량을 FLIPR Ca2+4 염료를 이용하여 측정하였다. PKC-α 억제제인 BIS(bisindolylmaleimide I)을 10 nM로 처리하였을 때, HL 추출물에 의하여 증가 되었던 Ca2 + 유입량이 감소하는 것을 확인하였다(도 8). 이는 HL의 TRPV1의 활성화가 PKC-의존 경로에 의한 것이라고 보여진다.
It was measured by processing the inhibitors of PKC-α, and using a Ca + 2
이상으로 본 발명의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
Claims (8)
Lactuca The present invention relates to a composition for preventing, treating or improving TRPV1 (Transient Receptor Potential channel, vanilloid subfamily member 1) -mediated disease.
The composition according to claim 1, wherein the TRPV1-mediated disease is pain, respiratory disease or lower urinary tract disease.
2. The composition of claim 1, wherein said composition activates TRPV1.
2. The composition of claim 1, wherein the composition increases the inflow of intracellular calcium ions.
2. The composition of claim 1, wherein the composition increases cell membrane potential.
The composition of claim 1, wherein said composition phosphorylates PKC-alpha (Protein Kinase C-alpha).
The composition of claim 1, wherein the composition is a food composition, a functional food composition, or a pharmaceutical composition.
(a) TRPV1을 포함하는 세포에 상기 제 1 항 내지 제 7 항 중 어느 한 항의 조성물 및 분석하고자 하는 시료를 접촉시키는 단계; 및
(b) 상기 조성물을 단독처리한 세포와 비교하여 상기 TRPV1의 활성이 감소-조절 되는 것으로 측정되는 경우에는 상기 시료는 TRPV1 길항제로 판정된다.An antagonist screening method of TRIPV1 (Transient Receptor Potential channel, Vanilloid subfamily member 1) comprising the following steps:
(a) contacting a cell containing TRPV1 with the composition of any one of claims 1 to 7 and a sample to be analyzed; And
(b) the sample is determined to be a TRPV1 antagonist if it is determined that the activity of said TRPV1 is reduced-regulated relative to cells that have been treated with said composition alone.
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