KR20230055867A - Phamaceutical composition for preventing or treating chronic obstructive pulmonary disease comprising Todarodes pacificus extract as an active ingredient - Google Patents
Phamaceutical composition for preventing or treating chronic obstructive pulmonary disease comprising Todarodes pacificus extract as an active ingredient Download PDFInfo
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- KR20230055867A KR20230055867A KR1020210139752A KR20210139752A KR20230055867A KR 20230055867 A KR20230055867 A KR 20230055867A KR 1020210139752 A KR1020210139752 A KR 1020210139752A KR 20210139752 A KR20210139752 A KR 20210139752A KR 20230055867 A KR20230055867 A KR 20230055867A
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- extract
- chronic obstructive
- obstructive pulmonary
- pulmonary disease
- squid
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Abstract
Description
본 발명은 살오징어 추출물을 유효성분으로 포함하는 만성 폐쇄성 폐질환의 예방 또는 치료용 조성물 등에 관한 것이다.The present invention relates to a composition for preventing or treating chronic obstructive pulmonary disease, including a cuttlefish extract as an active ingredient.
살오징어(Todarodes pacificus)는 우리나라 전 연안에 서식하고 있지만 주로 겨울철 동해 연안에서 많이 어획되는 가장 대표적인 극동 해역의 오징어류이다. 다리를 포함한 몸통길이는 보통 30cm 전후인 개체가 많으나 성장속도가 빠르고 회유성 종이므로, 언제 어느 해역에서 발견되느냐에 따라 다양한 크기의 개체들이 나타낸다. 우리가 식용으로 하는 대부분의 오징어가 본 종이며 주로 채낚기어업에 의해 야간에 어획된다.Cuttlefish ( Todarodes pacificus ) inhabits all coastal areas of Korea, but is the most representative squid of the Far Eastern region, mainly caught in the East Sea during winter. There are many individuals whose body length including legs is usually around 30 cm, but since it is a migratory species with a fast growth rate, individuals of various sizes appear depending on when and in which sea area it is found. Most of the squid we eat for food are this species, and they are mainly caught at night by jigging fisheries.
만성 폐쇄성 폐질환(chronic obstructive pulmonary disease; COPD)이란, 유해한 입자(담배 등)나 가스의 흡입에 의해 발생하는 폐의 비정상적인 염증반응과 이에 동반되어 완전히 가역적이지 않으며 점차 진행하는 기류제한을 특징으로 하는 호흡기 질환을 말하는 것이다. 이러한 만성 폐쇄성 폐질환에는 폐기종(emphysema), 만성기관지염(chronic bronchitis) 등이 포함된다. Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal inflammatory response in the lungs caused by inhalation of harmful particles (such as cigarettes) or gases, accompanied by not completely reversible and progressive airflow limitation. I mean respiratory disease. These chronic obstructive pulmonary diseases include emphysema, chronic bronchitis, and the like.
상기 만성 폐쇄성 폐질환은 흡연율 증가 및 평균 수명의 연장으로 인하여 발병률 및 사망률이 증가하는 추세로서, 우리나라에서 10대 사망 원인 중 하나이다. 만성 폐쇄성 폐질환 중 하나인 폐기종은 말초 기도 부위 폐포의 손상 및 말단 세 기관지의 폐포 간 공간 벽이 탄성을 잃고 파괴되어 비정상적으로 영구 확장됨으로써, 폐의 산소-이산화탄소 교환 능력이 감소되어 호흡 곤란이 발생하는 질환이다. 폐기종의 주요 원인은 흡연으로 알려져 있으나, 대기 오염이나 유해 작업 환경의 노출에 의해서도 생길 수 있으며, 호흡기 감염과 동반 시 진행 속도가 가속화되는 것으로 알려져 있다. 폐기종의 주요 증상인 조직 파괴로 인한 폐포 확장 증상은, 기질금속단백질분해효소(matrix metalloproteinase; MMP), 호중구 엘라스타제(neutrophil elastase) 등의 단백질 분해효소의 발현은 활성화되는 반면, 단백질 분해 효소를 억제하는 α1-항트립신(α1-antitrypsin)의 발현은 감소되기 때문인 것으로 알려졌다. 또한, 흡연에 의하여 폐포 내 대식세포 및 상피에서 다양한 사이토카인(cytokine) 및 케모카인(chemokine)의 분비가 유도되어 염증 반응이 활성화되면서 염증 관련 세포들에 의한 사이토카인/케모카인(TNF-α, IL-1β, IL-8, MCP-1, IFN-γ 등), 활성산소종(reactive oxygen species; ROS) 등의 생성이 증가되고, 이로 인하여 단백질 분해효소들의 발현 증가 및 활성화로 인하여 조직 손상이 가속화되는 것으로 알려져있다. 이러한 폐기종은 폐 구조가 비가역적으로 손상되는 질환으로 근원적 치료가 불가능하다. 현재 사용되는 치료제로는 염증 반응 완화를 위한 스테로이드 제제, 호흡곤란 작용 완화를 위한 기관지 확장제, 거담제 등 증상에 따른 대증적 치료 방법만이 사용되고 있는 실정이다.Chronic obstructive pulmonary disease is one of the top 10 causes of death in Korea, with an increasing incidence and mortality rate due to an increase in smoking rate and an extension of average life expectancy. In emphysema, one of the chronic obstructive pulmonary diseases, damage to the alveoli in the peripheral airways and the walls of the interalveolar spaces in the terminal bronchioles lose their elasticity and are destroyed, resulting in abnormal and permanent expansion. is a disease that The main cause of emphysema is known to be smoking, but it can also be caused by air pollution or exposure to hazardous work environments, and it is known that the rate of progression is accelerated when accompanied by respiratory infections. In the main symptom of emphysema, alveolar enlargement due to tissue destruction, expression of proteolytic enzymes such as matrix metalloproteinase (MMP) and neutrophil elastase are activated, whereas proteolytic enzymes It is known that the expression of α1-antitrypsin, which inhibits it, is reduced. In addition, smoking induces the secretion of various cytokines and chemokines from macrophages and epithelium in the alveoli, activating the inflammatory response, and cytokines/chemokines (TNF-α, IL- 1β, IL-8, MCP-1, IFN-γ, etc.), reactive oxygen species (ROS), etc. are increased, which accelerates tissue damage due to increased expression and activation of proteolytic enzymes. is known to be Emphysema is a disease in which the lung structure is irreversibly damaged and cannot be fundamentally treated. As currently used therapeutic agents, only symptomatic treatment methods according to symptoms such as steroid preparations for relieving inflammatory reactions, bronchodilators for relieving respiratory distress, and expectorants are used.
따라서, 이러한 만성 폐쇄성 폐질환을 효과적으로 치료하기 위해서는 폐 구조의 손상 속도를 감소시키거나, 폐 조직 손상을 억제할 수 있는 치료제의 개발이 절실히 필요한 실정이다.Therefore, in order to effectively treat chronic obstructive pulmonary disease, there is an urgent need to develop a therapeutic agent capable of reducing the rate of damage to lung structures or inhibiting lung tissue damage.
본 발명은 상기와 같은 종래 기술상의 문제점을 해결하기 위해 안출된 것으로, 살오징어 추출물을 유효성분으로 포함하는 조성물이 폐 조직의 손상 및 염증 반응을 효과적으로 억제함을 확인하여 만성 폐쇄성 폐질환의 예방 또는 치료효과를 확인한 바, 이에 기초하여 본 발명을 완성하였다.The present invention was made to solve the above problems in the prior art, and it was confirmed that a composition containing a cuttlefish extract as an active ingredient effectively inhibits lung tissue damage and inflammatory response, thereby preventing or preventing chronic obstructive pulmonary disease. The therapeutic effect was confirmed, and based on this, the present invention was completed.
이에 본 발명의 목적은 살오징어 추출물을 유효성분으로 포함하는, 만성 폐쇄성 폐질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating chronic obstructive pulmonary disease, comprising a squid extract as an active ingredient.
본 발명의 다른 목적은 살오징어 추출물을 유효성분으로 포함하는, 만성 폐쇄성 폐질환의 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 chronic obstructive pulmonary disease, comprising a squid extract as an active ingredient.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당해 기술분야에서 통상의 지식을 가진 자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.
상기 본 발명의 목적을 달성하기 위하여, 본 발명은 살오징어 추출물을 유효성분으로 포함하는, 만성 폐쇄성 폐질환의 예방 또는 치료용 약학적 조성물을 제공한다.In order to achieve the above object of the present invention, the present invention provides a pharmaceutical composition for preventing or treating chronic obstructive pulmonary disease, comprising a cuttlefish extract as an active ingredient.
또한, 본 발명은 살오징어 추출물을 유효성분으로 포함하는, 만성 폐쇄성 폐질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving chronic obstructive pulmonary disease, comprising a cuttlefish extract as an active ingredient.
또한, 본 발명은 살오징어 추출물을 유효성분으로 포함하는 조성물을 개체에 투여하는 단계를 포함하는, 만성 폐쇄성 폐질환의 예방 또는 치료 방법을 제공한다. In addition, the present invention provides a method for preventing or treating chronic obstructive pulmonary disease, comprising administering to a subject a composition containing a cuttlefish extract as an active ingredient.
또한, 본 발명은 살오징어 추출물을 유효성분으로 포함하는 조성물의 만성 폐쇄성 폐질환의 예방 또는 치료 용도를 제공한다. In addition, the present invention provides a preventive or therapeutic use of a composition containing a cuttlefish extract as an active ingredient for chronic obstructive pulmonary disease.
또한, 본 발명은 만성 폐쇄성 폐질환의 예방 또는 치료 약제 제조를 위한 살오징어 추출물의 용도를 제공한다.In addition, the present invention provides the use of the cuttlefish extract for preparing a drug for preventing or treating chronic obstructive pulmonary disease.
본 발명의 일 구현예에서 상기 만성 폐쇄성 폐질환은 폐기종(emphysema)일 수 있으나, 이에 제한되는 것은 아니다.In one embodiment of the present invention, the chronic obstructive pulmonary disease may be emphysema, but is not limited thereto.
본 발명의 다른 구현예에서 상기 살오징어 추출물은 하기 증상 중 하나 이상을 억제 또는 개선할 수 있으나, 이에 제한되는 것은 아니다:In another embodiment of the present invention, the squid extract can inhibit or improve one or more of the following symptoms, but is not limited thereto:
i) 폐 유순도의 증가; 및i) increase in lung compliance; and
ii) 폐 탄성도의 감소.ii) a decrease in lung elasticity.
본 발명의 또 다른 구현예에서 상기 살오징어 추출물은 TNF-α, IL-1β, 및 IL-6으로 이루어지는 군으로부터 선택된 하나 이상의 염증성 사이토카인의 발현을 억제할 수 있으나, 이에 제한되는 것은 아니다.In another embodiment of the present invention, the squid extract can inhibit the expression of one or more inflammatory cytokines selected from the group consisting of TNF-α, IL-1β, and IL-6, but is not limited thereto.
본 발명의 또 다른 구현예에서 상기 살오징어 추출물은 Nos2의 발현을 억제할 수 있으나, 이에 제한되는 것은 아니다.In another embodiment of the present invention, the squid extract can inhibit the expression of Nos2, but is not limited thereto.
본 발명의 또 다른 구현예에서 상기 살오징어 추출물은 물, C1 내지 C4의 알코올, 에틸아세테이트, 클로로포름, 헥산, 및 이들의 혼합용매로 이루어지는 군으로부터 선택된 하나 이상의 용매로 추출될 수 있으나, 이에 제한되는 것은 아니다.In another embodiment of the present invention, the squid extract may be extracted with one or more solvents selected from the group consisting of water, C 1 to C 4 alcohol, ethyl acetate, chloroform, hexane, and mixed solvents thereof, but It is not limited.
본 발명의 또 다른 구현예에서 상기 살오징어 추출물은 살오징어 다리 추출물일 수 있으나, 이에 제한되는 것은 아니다.In another embodiment of the present invention, the squid extract may be a squid leg extract, but is not limited thereto.
본 발명의 살오징어 추출물을 유효성분으로 포함하는 조성물은 염증성 사이토카인 TNF-α, IL-1β, 및 IL-6의 발현과 염증성 효소 Nos2의 발현을 억제하며, 폐 조직의 손상 및 염증 반응을 효과적으로 억제하는 바, 폐기종을 포함하는 만성 폐쇄성 폐질환의 치료 및 예방에 폭 넓게 사용 가능할 것으로 기대된다.The composition containing the squid extract of the present invention as an active ingredient inhibits the expression of inflammatory cytokines TNF-α, IL-1β, and IL-6 and the expression of the inflammatory enzyme Nos2, and effectively reduces lung tissue damage and inflammatory response. As a result, it is expected to be widely used for the treatment and prevention of chronic obstructive pulmonary diseases including emphysema.
도 1는 본 발명의 일 실시예에 따른 마우스 유래 대식세포에서 살오징어 추출물(2-86) 처리에 따른 NO 생성을 아질산염 농도로 환산한 결과를 나타낸 것이다.
도 2는 본 발명의 일 실시예에 따른 마우스 유래 대식세포에서 살오징어 추출물 처리에 따른 활성산소종(reactive oxygen species; ROS)을 측정한 결과를 나타낸 것이다.
도 3은 본 발명의 일 실시예에 따른 마우스 유래 대식세포에서 살오징어 추출물 처리에 따른 세포 생존율을 나타낸 것이다.
도 4는 본 발명의 일 실시예에 따른 마우스 유래 대식세포에서 mRNA를 분리하여, 살오징어 추출물 처리에 따른 염증성 효소 Nos2(nitric oxide synthase 2)와 염증성 사이토카인 TNF-α(tumor necrosis factor-α)의 발현 억제 효과를 확인한 결과를 나타낸 것이다.
도 5는 본 발명의 일 실시예에 따른 마우스 유래 대식세포에서 mRNA를 분리하여, 살오징어 추출물 처리에 따른 염증성 사이토카인 IL-1β(interleukin 1 beta) 및 IL-6(interleukin 6)의 발현 억제 효과를 확인한 결과를 나타낸 것이다.
도 6은 본 발명의 일 실시예에 따른 폐기종 마우스 모델에서 FlexiVent RM를 이용하여, 살오징어 추출물 처리에 따른 폐 유순도 감소 및 폐 탄성도 증가의 효과를 확인한 결과를 나타낸 것이다.
도 7은 본 발명의 일 실시예에 따른 폐기종 마우스 모델에서 H&E 염색을 통해, 살오징어 추출물 처리에 따른 폐조직 손상 억제 효과를 확인한 결과를 나타낸 것이다.
도 8은 본 발명의 일 실시예에 따른 폐기종 마우스 모델에서 FlexiVent RM를 이용하여, 살오징어 추출물 처리에 따른 폐 유순도 감소 및 폐 탄성도 증가의 효과를 확인하여, 이미 생성된 폐기종에 대한 치료 효과를 나타낸 것이다.
도 9는 본 발명의 일 실시예에 따른 폐기종 마우스 모델에서 H&E 염색을 통해, 살오징어 추출물 처리에 따른 폐조직 손상 억제 효과를 확인하여, 이미 생성된 폐기종에 대한 치료 효과를 나타낸 것이다.Figure 1 shows the result of NO production in terms of nitrite concentration according to the treatment of squid extract (2-86) in mouse-derived macrophages according to an embodiment of the present invention.
Figure 2 shows the results of measuring reactive oxygen species (ROS) in mouse-derived macrophages according to an embodiment of the present invention according to the treatment of the squid extract.
Figure 3 shows the cell viability according to the cuttlefish extract treatment in mouse-derived macrophages according to an embodiment of the present invention.
Figure 4 isolates mRNA from mouse-derived macrophages according to an embodiment of the present invention, inflammatory enzyme Nos2 (nitric oxide synthase 2) and inflammatory cytokine TNF-α (tumor necrosis factor-α) according to cuttlefish extract treatment It shows the result of confirming the expression inhibition effect of.
Figure 5 isolates mRNA from mouse-derived macrophages according to an embodiment of the present invention, and the effect of suppressing the expression of inflammatory cytokines IL-1β (interleukin 1 beta) and IL-6 (interleukin 6) according to the cuttlefish extract treatment It shows the result of checking .
Figure 6 shows the results of confirming the effect of reducing lung compliance and increasing lung elasticity according to the treatment with a squid extract using FlexiVent RM in an emphysema mouse model according to an embodiment of the present invention.
Figure 7 shows the results of confirming the effect of suppressing lung tissue damage according to the treatment with the salmon fish extract through H&E staining in an emphysema mouse model according to an embodiment of the present invention.
8 shows the effect of reducing lung compliance and increasing lung elasticity according to squid extract treatment using FlexiVent RM in an emphysema mouse model according to an embodiment of the present invention, thereby demonstrating a therapeutic effect on emphysema already generated it is shown
Figure 9 shows the therapeutic effect on previously formed emphysema by confirming the effect of inhibiting lung tissue damage according to the treatment with the salmon fish extract through H&E staining in an emphysema mouse model according to an embodiment of the present invention.
본 발명의 다른 실시예에서는 마우스 유래 대식세포에 살오징어 추출물을 처리한 후, NO 생성 억제 효과를 확인하여 살오징어 추출물의 항염증 효과를 확인하였다(실시예 2 참조).In another embodiment of the present invention, the anti-inflammatory effect of the squid extract was confirmed by treating mouse-derived macrophages with the squid extract, and then confirming the NO production inhibitory effect (see Example 2).
본 발명의 또 다른 실시예에서는 마우스 유래 대식세포에 살오징어 추출물을 처리한 후, ROS 생성 억제를 확인하여 살오징어 추출물의 항산화 효과를 확인하였다(실시예 3 참조).In another embodiment of the present invention, after treating mouse-derived macrophages with the squid extract, the inhibition of ROS production was confirmed to confirm the antioxidant effect of the squid extract (see Example 3).
본 발명의 일 실시예에서는 RAW 264.7 세포에 살오징어 추출물을 처리한 후, 세포의 생존율을 분석하여 살오징어 추출물의 세포 독성이 낮은 것을 확인하였다(실시예 4 참조).In one embodiment of the present invention, after treating raw squid extract to RAW 264.7 cells, cell viability was analyzed to confirm that the cytotoxicity of raw squid extract was low (see Example 4).
본 발명의 또 다른 실시예에서는 마우스 유래 대식세포에 살오징어 추출물을 처리한 후, 염증성 사이토카인 및 염증성 효소 발현 억제 효과를 확인하였다(실시예 5 참조).In another embodiment of the present invention, mouse-derived macrophages were treated with a squid extract, and then the effect of inhibiting the expression of inflammatory cytokines and inflammatory enzymes was confirmed (see Example 5).
본 발명의 또 다른 실시예에서는 폐기종 마우스 모델에서 살오징어 추출물 처리에 따른 폐 유순도의 감소, 폐 탄성도의 증가, 및 폐 조직 손상의 감소 억제 효과를 확인하였다(실시예 6 참조).In another embodiment of the present invention, reduction of lung compliance, increase of lung elasticity, and inhibition of lung tissue damage were confirmed by treatment with squid extract in an emphysema mouse model (see Example 6).
본 발명의 또 다른 실시예에서는 폐기종 마우스 모델에서 살오징어 추출물 처리에 따른 폐 유순도의 감소, 폐 탄성도의 증가, 및 폐 조직 손상의 감소 억제 효과를 확인하여, 이미 생성된 폐기종에 대한 치료 효과를 확인하였다(실시예 7 참조).In another embodiment of the present invention, the reduction of lung compliance, the increase of lung elasticity, and the inhibitory effect on the reduction of lung tissue damage according to the treatment of squid extract in an emphysema mouse model were confirmed, and the therapeutic effect on the already generated emphysema was confirmed. confirmed (see Example 7).
이하, 본 발명에 대해 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 살오징어 추출물을 유효성분으로 포함하는, 만성 폐쇄성 폐질환의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating chronic obstructive pulmonary disease, comprising a cuttlefish extract as an active ingredient.
본 명세서에 있어서, “만성 폐쇄성 폐질환(chronic obstructive pulmonary disease; COPD)”이란 유해한 입자(담배 등)나 가스의 흡입에 의해 발생하는 폐의 비정상적인 염증반응과 이에 동반되어 완전히 가역적이지 않으며 점차 진행하는 기류제한을 특징으로 하는 호흡기 질환을 말하는 것이다. 상기 만성 폐쇄성 폐질환은 폐기종, 만성 기관지염(chronic bronchitis), 만성 폐쇄성 기관지염(Chronic obstructive bronchitis) 또는 만성 세기관지염(Chronic bronchiolitis)을 포함할 수 있으나, 이에 제한되지 않는다. 또한, 본 발명의 일 실시예에 따르면 폐기종일 수 있으나, 이에 제한되지 않는다.As used herein, “chronic obstructive pulmonary disease (COPD)” refers to an abnormal inflammatory response of the lungs caused by inhalation of harmful particles (such as cigarettes) or gases, accompanied by an abnormal inflammatory response that is not completely reversible and gradually progresses. It is a respiratory disease characterized by airflow limitation. The chronic obstructive pulmonary disease may include emphysema, chronic bronchitis, chronic obstructive bronchitis or chronic bronchiolitis, but is not limited thereto. Also, according to an embodiment of the present invention, it may be emphysema, but is not limited thereto.
본 명세서에 있어서, "폐기종(emphysema)"은 말초 기도 부위 폐포의 손상 및 말단 세 기관지의 폐포 간 공간 벽이 탄성을 잃고 파괴되어 비정상적으로 영구 확장됨으로써, 폐의 산소-이산화탄소 교환 능력이 감소되어 호흡 곤란이 발생하는 질환이다. 폐기종은 흡연 등으로 인하여 폐포 내 대식세포 및 상피에서 다양한 사이토카인(cytokine) 및 케모카인(chemokine)의 분비가 유도되어 염증 반응이 활성화되면서 진행된다. 폐기종은 염증 관련 세포들에 의한 사이토카인/케모카인(TNF-α, IL-1β, IL-8, MCP-1, IFN-γ 등), 활성산소종(reactive oxygen species; ROS), 산화질소 합성효소 등의 생성이 증가되고, 이로 인하여 단백질 분해효소들의 발현이 증가 및 활성화되어 조직 손상이 가속화 된다.As used herein, "emphysema" refers to damage of the alveoli in the peripheral airway and the walls of the interalveolar space of the terminal bronchioles lose their elasticity and are destroyed, resulting in abnormal and permanent expansion, thereby reducing the oxygen-carbon dioxide exchange capacity of the lungs and breathing. It is a disease that causes trouble. Emphysema progresses when the secretion of various cytokines and chemokines is induced in alveolar macrophages and epithelium due to smoking, etc., and an inflammatory response is activated. Emphysema is caused by cytokines/chemokines (TNF-α, IL-1β, IL-8, MCP-1, IFN-γ, etc.), reactive oxygen species (ROS), and nitric oxide synthase by inflammation-related cells. The production of back is increased, and as a result, the expression of proteolytic enzymes is increased and activated, thereby accelerating tissue damage.
본 명세서에 있어서, “살오징어(Todarodes pacificus)"는 우리나라 전 연안에 서식하고 있지만 주로 겨울철 동해 연안에서 많이 어획되는 가장 대표적인 극동 해역의 오징어류이다. 다리를 포함한 몸통길이는 보통 30cm 전후인 개체가 많으나 성장속도가 빠르고 회유성 종이므로 언제 어느 해역에서 발견되느냐에 따라 다양한 크기의 개체들이 나타낸다. 우리가 식용으로 하는 대부분의 오징어가 본 종이며 주로 채낚기어업에 의해 야간에 어획된다. 상기 살오징어 추출물은 머리, 눈, 입, 다리, 내장, 먹물 주머니, 아가미, 또는 이를 모두 포함한 해산물 전체 추출물일 수 있으며, 본 발명의 일 실시예에 따르면 살오징어 다리 추출물일 수 있으나, 이에 제한되지 않는다. 상기 살오징어는 직접 양식한 것 또는 시판되는 것 등을 제한 없이 사용할 수 있다.In this specification, "Squid ( Todarodes pacificus )" is the most representative Far Eastern squid, which lives in all coastal areas of Korea, but is mainly caught in the East Sea during winter. There are many individuals whose body length including legs is usually around 30 cm, but It grows rapidly and is a migratory species, so individuals of various sizes appear depending on when and in which sea area it is found.Most of the squid we eat are this species and are mainly caught at night by jigging fisheries.The above-mentioned squid extract is the head , Eyes, mouth, legs, intestines, ink sacs, gills, or whole seafood extracts including all of them, and according to an embodiment of the present invention, it may be a squid leg extract, but is not limited thereto. Farmed directly or commercially available can be used without limitation.
본 발명에 있어서, "추출물"은 상기 살오징어의 추출처리에 의하여 얻어지는 추출액, 상기 추출액의 희석액이나 농축액, 상기 추출액을 건조하여 얻어지는 건조물, 상기 추출액의 조정제물이나 정제물, 또는 이들의 혼합물 등, 추출액 자체 및 추출액을 이용하여 형성 가능한 모든 제형의 추출물을 포함한다. 또한, “추출물”에는 조 추출물, 극성용매 가용 추출물 또는 비극성 용매 가용 추출물 등이 포함될 수 있다. In the present invention, "extract" refers to an extract obtained by the extraction of the squid, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, a crude or purified product of the extract, or a mixture thereof, It includes the extract itself and extracts of all formulations that can be formed using the extract. In addition, “extract” may include a crude extract, a polar solvent-soluble extract, or a non-polar solvent-soluble extract.
본 발명에 있어서, 상기 살오징어를 추출하는 방법은 특별히 제한되지 아니하며, 당해 기술분야에서 통상적으로 사용하는 방법에 따라 추출할 수 있다. 예를 들어, 초임계추출, 아임계추출, 고온추출, 고압 추출, 초음파추출법 또는 소니케이션 추출법 등의 추출 장치를 이용한 방법 또는 XAD 및 HP-20을 포함한 흡착 수지를 이용하는 방법 등을 이용할 수 있다. 상기 추출 방법의 비제한적인 예로는, 가열추출법, 냉침추출법, 환류냉각추출법, 수증기증류법, 초음파추출법, 소니케이션 추출법, 용출법, 압착법, 용매 추출법 등을 들 수 있으며, 이들은 단독으로 수행되거나 2 종 이상의 방법을 병용하여 수행될 수 있다. 본 발명의 일 실시예에 따르면, 상기 살오징어 추출물은 용매 추출법을 사용할 수 있으나, 이에 제한되지 않는다. In the present invention, the method for extracting the squid is not particularly limited, and can be extracted according to a method commonly used in the art. For example, a method using an extraction device such as supercritical extraction, subcritical extraction, high temperature extraction, high pressure extraction, ultrasonic extraction or sonication extraction, or a method using an adsorbent resin including XAD and HP-20 may be used. Non-limiting examples of the extraction method include a heating extraction method, a cold extraction method, a reflux cooling extraction method, a steam distillation method, an ultrasonic extraction method, a sonication extraction method, an elution method, a compression method, a solvent extraction method, and the like, which are performed alone or in two It can be performed using a combination of more than one method. According to one embodiment of the present invention, the squid extract may use a solvent extraction method, but is not limited thereto.
또한, 목적에 따라서 추출물은 추가적으로 통상의 분획 공정을 수행할 수 있으며, 통상의 정제 방법에 따라 정제될 수 있다. 예를 들어, 본 발명의 조성물에 포함되는 추출물은 상기의 용매 추출법으로 추출된 1차 추출물을 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가 과정을 통해 분말화하여 제조할 수 있다. 또한, 상기 1차 추출물을 진공감압농축하여 물과 섞어서 분획물을 얻을 수 있다. 그 후, 사이즈 배제 크로마토그래피(Size exclusion chromatography), 고성능 액체 크로마토그래피(high-performance liquid chromatography), 실리카겔 컬럼 크로마토그래피(silica gel column chromatography), 박층 크로마토그래피(thin layer chromatography) 등의 다양한 크로마토그래피를 통해 추가적으로 정제 분획을 얻을 수 있다. 따라서 본 발명에 있어서 추출물은 추출, 분획 또는 정제의 각 단계에서 얻어지는 모든 추출액, 분리 화합물, 분획 및 정제물, 이들의 희석, 농축, 건조물 등이 포함될 수 있다.In addition, depending on the purpose, the extract may be additionally subjected to a conventional fractionation process and may be purified according to a conventional purification method. For example, the extract included in the composition of the present invention may be prepared by pulverizing the primary extract extracted by the solvent extraction method through an additional process such as distillation under reduced pressure and freeze drying or spray drying. In addition, fractions may be obtained by concentrating the primary extract under reduced pressure and mixing with water. After that, various chromatography such as size exclusion chromatography, high-performance liquid chromatography, silica gel column chromatography, and thin layer chromatography are performed. Through this, an additional purified fraction can be obtained. Therefore, in the present invention, the extract may include all extracts, separated compounds, fractions and purified products obtained in each step of extraction, fractionation or purification, dilution, concentration, or drying thereof.
본 발명에서 상기 살오징어를 추출하는 데에 사용되는 추출 용매의 종류는 특별히 제한되지 아니하며, 천연물로부터 추출물을 추출하는 당업계에 공지된 통상적인 방법에 따라, 즉, 통상적인 온도, 압력의 조건 하에서 통상적인 용매를 사용하여 추출할 수 있다. 예를 들어, 본 발명에 있어서 상기 살오징어 추출물은 물, C1 내지 C4의 알코올, 에틸아세테이트, 클로로포름, 헥산, 및 이들의 혼합용매로 이루어지는 군에서 선택된 하나 이상의 용매로 추출될 수 있으며, 본 발명의 일 실시예에 따르면 에탄올을 용매로 사용하여 추출할 수 있으나, 이에 제한되지 않는다.In the present invention, the type of extraction solvent used to extract the squid is not particularly limited, and according to a conventional method known in the art for extracting an extract from a natural product, that is, under normal temperature and pressure conditions. It can be extracted using a common solvent. For example, in the present invention, the squid extract may be extracted with one or more solvents selected from the group consisting of water, C 1 to C 4 alcohol, ethyl acetate, chloroform, hexane, and mixed solvents thereof, According to one embodiment of the invention, extraction may be performed using ethanol as a solvent, but is not limited thereto.
본 발명에 있어서, 상기 에탄올을 용매로 사용하여 살오징어를 추출할 경우, 예를 들어, 1 % 내지 100 % 에탄올, 1 % 내지 80 % 에탄올, 1 % 내지 60 % 에탄올, 1 % 내지 40 % 에탄올, 1 % 내지 25 % 에탄올, 5 % 내지 100 % 에탄올, 5 % 내지 80 % 에탄올, 5 % 내지 60 % 에탄올, 5 % 내지 40 % 에탄올, 5 % 내지 25 % 에탄올, 10 % 내지 100 % 에탄올, 10 % 내지 80 % 에탄올, 10 % 내지 60 % 에탄올, 10 % 내지 40 % 에탄올, 10 % 내지 25 % 에탄올, 15 % 내지 100 % 에탄올, 15 % 내지 80 % 에탄올, 15 % 내지 60 % 에탄올, 15 % 내지 40 % 에탄올, 또는 15 % 내지 25 % 에탄올을 사용할 수 있으며, 본 발명의 일 실시예에 따르면 20 % 에탄올일 수 있으나, 이에 제한되지 않는다.In the present invention, when the squid is extracted using the ethanol as a solvent, for example, 1% to 100% ethanol, 1% to 80% ethanol, 1% to 60% ethanol, 1% to 40% ethanol , 1% to 25% ethanol, 5% to 100% ethanol, 5% to 80% ethanol, 5% to 60% ethanol, 5% to 40% ethanol, 5% to 25% ethanol, 10% to 100% ethanol, 10% to 80% Ethanol, 10% to 60% Ethanol, 10% to 40% Ethanol, 10% to 25% Ethanol, 15% to 100% Ethanol, 15% to 80% Ethanol, 15% to 60% Ethanol, 15 % to 40% ethanol, or 15% to 25% ethanol may be used, and according to one embodiment of the present invention, it may be 20% ethanol, but is not limited thereto.
상기 제조된 추출물은 이후 여과하거나 농축 또는 건조과정을 수행하여 용매를 제거할 수 있으며, 여과, 농축 및 건조를 모두 수행할 수 있다. 예를 들어, 여과는 여과지를 이용하거나 감압여과기를 이용할 수 있으며, 농축은 진공 감압 농축기 또는 진공회전증발기를 이용할 수 있고, 건조는 감압건조, 진공건조, 비등건조, 분무건조, 동결건조법 등을 수행할 수 있으나, 이에 제한되는 것은 아니다.The prepared extract may then be filtered or concentrated or dried to remove the solvent, and both filtration, concentration and drying may be performed. For example, filtration may use filter paper or a vacuum filter, concentration may use a vacuum vacuum concentrator or vacuum rotary evaporator, and drying may be performed by vacuum drying, vacuum drying, boiling drying, spray drying, freeze drying, and the like. It can be done, but is not limited thereto.
본 명세서에 있어서, 상기 살오징어 추출물은 폐 유순도의 증가 또는 폐 탄성도의 감소의 증상을 억제 또는 개선할 수 있으나, 이에 제한되지 않는다. 구체적으로, 상기 살오징어 추출물은 엘라스타제(elastase)에 의한 폐 유순도 증가를 정상 수준으로 회복시킬 수 있으나, 이에 제한되지 않는다. 상기 정상 수준이란 엘라스타제에 의한 폐 유순도 증가를 감소시켜, 엘라스타제를 처리하지 않은 대조군의 폐 유순도와 유의적인 차이가 없게 되는 것을 의미한다. In the present specification, the squid extract may suppress or improve symptoms of an increase in lung compliance or a decrease in lung elasticity, but is not limited thereto. Specifically, the squid extract may restore the increase in lung compliance by elastase to a normal level, but is not limited thereto. The normal level means that the increase in lung compliance by elastase is reduced, so that there is no significant difference from the lung compliance of the control group not treated with elastase.
또한, 구체적으로, 상기 살오징어 추출물은 엘라스타제(elastase)에 의한 폐 탄성도 감소를 정상 수준으로 회복시킬 수 있으나, 이에 제한되지 않는다. 상기 정상 수준이란 엘라스타제에 의한 폐 탄성도 감소를 증가시켜, 엘라스타제를 처리하지 않은 대조군의 폐 탄성도와 유의적인 차이가 없게 되는 것을 의미한다.In addition, specifically, the squid extract may restore the reduction in lung elasticity caused by elastase to a normal level, but is not limited thereto. The normal level means that the decrease in lung elasticity caused by elastase is increased so that there is no significant difference from the lung elasticity of the control group not treated with elastase.
또한, 상기 살오징어 추출물은 염증 관련 사이토카인(TNF-α, IL-1β, IL-6 등) 또는 염증성 효소(Nos2 등)의 발현을 억제할 수 있으나, 이에 제한되지 않는다.In addition, the squid extract may inhibit the expression of inflammation-related cytokines (TNF-α, IL-1β, IL-6, etc.) or inflammatory enzymes (Nos2, etc.), but is not limited thereto.
본 명세서에 있어서, "폐 유순도(compliance)"는 폐 내의 단위 압력의 변화에 따른 부피의 변화를 의미한다. 폐기종의 경우에 폐포 간 공간 벽이 탄성을 잃고 파괴되어 비정상적으로 영구 확장되는 바, 폐 유순도는 증가한다. In the present specification, "lung compliance" means a change in volume according to a change in unit pressure in the lung. In the case of emphysema, the walls of the interalveolar space lose their elasticity and are destroyed, resulting in abnormal permanent dilatation, resulting in increased lung compliance.
본 명세서에 있어서, "폐 탄성도(tissue elastance)"는 횡경막의 근육 수축작용으로 호흡하는 능력으로, 폐 탄성도가 감소되면 기도가 무너지고 기류폐색이 일어난다. 폐기종의 경우에 폐포 간 공간 벽이 탄성을 잃고 파괴되는 바, 폐 탄성도가 감소한다.In this specification, "tissue elastance" is the ability to breathe by muscle contraction of the diaphragm, and when lung elasticity is reduced, the airway collapses and airflow obstruction occurs. In the case of emphysema, the walls of the interalveolar space lose their elasticity and are destroyed, resulting in a decrease in lung elasticity.
적합한 산의 예로는 염산, 브롬산, 황산, 질산, 과염소산, 푸마르산, 말레산, 인산, 글리콜산, 락트산, 살리실산, 숙신산, 톨루엔-p-설폰산, 타르타르산, 아세트산, 시트르산, 메탄설폰산, 포름산, 벤조산, 말론산, 글루콘산, 나프탈렌-2-설폰산, 벤젠설폰산 등을 들 수 있다. 산부가염은 통상의 방법, 예를 들면 화합물을 과량의 산 수용액에 용해시키고, 이 염을 메탄올, 에탄올, 아세톤 또는 아세토니트릴과 같은 수혼화성 유기 용매를 사용하여 침전시켜서 제조할 수 있다. 또한, 동몰량의 화합물 및 물 중의 산 또는 알코올을 가열하고 이어서 상기 혼합물을 증발시켜서 건조시키거나, 또는 석출된 염을 흡인 여과시켜 제조할 수 있다.Examples of suitable acids are hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, formic acid , benzoic acid, malonic acid, gluconic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid and the like. Acid addition salts can be prepared by conventional methods, for example, by dissolving a compound in an aqueous solution of excess acid and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. It can also be prepared by heating equimolar amounts of the compound and an acid or alcohol in water and then evaporating the mixture to dryness, or suction filtering the precipitated salt.
적합한 염기로부터 유도된 염은 나트륨, 칼륨 등의 알칼리 금속, 마그네슘 등의 알칼리 토금속, 및 암모늄 등을 포함할 수 있으나, 이에 제한되는 것은 아니다. 알칼리 금속 또는 알칼리 토금속염은, 예를 들면 화합물을 과량의 알칼리 금속 수산화물 또는 알칼리토 금속 수산화물 용액 중에 용해하고, 비용해 화합물염을 여과한 후 여액을 증발, 건조시켜 얻을 수 있다. 이 때, 금속염으로서는 특히 나트륨, 칼륨 또는 칼슘염을 제조하는 것이 제약상 적합하며, 또한 이에 대응하는 은염은 알칼리 금속 또는 알칼리토 금속염을 적당한 은염(예, 질산은)과 반응시켜 얻을 수 있다.Salts derived from suitable bases may include, but are not limited to, alkali metals such as sodium and potassium, alkaline earth metals such as magnesium, and ammonium. An alkali metal or alkaline earth metal salt can be obtained, for example, by dissolving a compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable for pharmaceutical purposes to prepare a sodium, potassium or calcium salt, and the corresponding silver salt can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).
본 발명의 조성물 내의 상기 살오징어 추출물의 함량은 질환의 증상, 증상의 진행 정도, 환자의 상태 등에 따라서 적절히 조절 가능하며, 예컨대, 전체 조성물 중량을 기준으로 0.0001 내지 99.9중량%, 또는 0.001 내지 50중량%일 수 있으나, 이에 한정되는 것은 아니다. 상기 함량비는 용매를 제거한 건조량을 기준으로 한 값이다.The content of the squid extract in the composition of the present invention can be appropriately adjusted according to the symptoms of the disease, the degree of progression of the symptoms, the condition of the patient, etc., for example, 0.0001 to 99.9% by weight, or 0.001 to 50% by weight based on the total weight of the composition. %, but is not limited thereto. The content ratio is a value based on the dry amount after removing the solvent.
본 발명의 조성물 내의 상기 살오징어 추출물은 1 내지 5000 μg/ml, 100 내지 5000 μg/ml, 150 내지 5000 μg/ml, 200 내지 5000 μg/ml, 1 내지 4000 μg/ml, 100 내지 4000 μg/ml, 150 내지 4000 μg/ml, 200 내지 4000 μg/ml, 1 내지 3000 μg/ml, 100 내지 3000 μg/ml, 150 내지 3000 μg/ml, 200 내지 3000 μg/ml, 1 내지 2000 μg/ml, 100 내지 2000 μg/ml, 150 내지 2000 μg/ml, 200 내지 2000 μg/ml, 1 내지 1500 μg/ml, 100 내지 1500 μg/ml, 150 내지 1500 μg/ml, 또는 200 내지 1500 μg/ml의 농도로 포함된 것일 수 있으나, 이에 제한되지 않는다.The squid extract in the composition of the present invention is 1 to 5000 μg / ml, 100 to 5000 μg / ml, 150 to 5000 μg / ml, 200 to 5000 μg / ml, 1 to 4000 μg / ml, 100 to 4000 μg / ml ml, 150 to 4000 μg/ml, 200 to 4000 μg/ml, 1 to 3000 μg/ml, 100 to 3000 μg/ml, 150 to 3000 μg/ml, 200 to 3000 μg/ml, 1 to 2000 μg/ml , 100 to 2000 μg/ml, 150 to 2000 μg/ml, 200 to 2000 μg/ml, 1 to 1500 μg/ml, 100 to 1500 μg/ml, 150 to 1500 μg/ml, or 200 to 1500 μg/ml It may be included at a concentration of, but is not limited thereto.
본 발명에 따른 약학적 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. 상기 부형제는 예를 들어, 희석제, 결합제, 붕해제, 활택제, 흡착제, 보습제, 필름-코팅 물질, 및 제어방출첨가제로 이루어진 군으로부터 선택된 하나 이상일 수 있다. The pharmaceutical composition according to the present invention may further include suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions. The excipient may be, for example, one or more selected from the group consisting of a diluent, a binder, a disintegrant, a lubricant, an adsorbent, a moisturizer, a film-coating material, and a controlled release additive.
본 발명에 따른 약학적 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 서방형 과립제, 장용과립제, 액제, 점안제, 엘실릭제, 유제, 현탁액제, 주정제, 트로키제, 방향수제, 리모나아데제, 정제, 서방형정제, 장용정제, 설하정, 경질캅셀제, 연질캅셀제, 서방캅셀제, 장용캅셀제, 환제, 틴크제, 연조엑스제, 건조엑스제, 유동엑스제, 주사제, 캡슐제, 관류액, 경고제, 로션제, 파스타제, 분무제, 흡입제, 패취제, 멸균주사용액, 또는에어로졸 등의 외용제 등의 형태로 제형화하여 사용될 수 있으며, 상기 외용제는 크림, 젤, 패치, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 또는 카타플라스마제 등의 제형을 가질 수 있다. The pharmaceutical compositions according to the present invention are powders, granules, sustained-release granules, enteric granules, solutions, eye drops, elsilic agents, emulsions, suspensions, spirits, troches, perfumes, and limonadese, respectively, according to conventional methods. , tablets, sustained-release tablets, enteric tablets, sublingual tablets, hard capsules, soft capsules, sustained-release capsules, enteric capsules, pills, tinctures, soft extracts, dry extracts, fluid extracts, injections, capsules, perfusate, It can be formulated and used in the form of external preparations such as warning agents, lotions, pasta agents, sprays, inhalants, patches, sterile injection solutions, or aerosols, and the external agents are creams, gels, patches, sprays, ointments, and warning agents. , lotion, liniment, pasta, or cataplasma may have formulations such as the like.
본 발명에 따른 약학적 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 올리고당, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. Carriers, excipients and diluents that may be included in the pharmaceutical composition according to the present invention include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
본 발명에 따른 정제, 산제, 과립제, 캡슐제, 환제, 트로키제의 첨가제로 옥수수전분, 감자전분, 밀전분, 유당, 백당, 포도당, 과당, 디-만니톨, 침강탄산칼슘, 합성규산알루미늄, 인산일수소칼슘, 황산칼슘, 염화나트륨, 탄산수소나트륨, 정제 라놀린, 미결정셀룰로오스, 덱스트린, 알긴산나트륨, 메칠셀룰로오스, 카르복시메칠셀룰로오스나트륨, 카올린, 요소, 콜로이드성실리카겔, 히드록시프로필스타치, 히드록시프로필메칠셀룰로오스(HPMC) 1928, HPMC 2208, HPMC 2906, HPMC 2910, 프로필렌글리콜, 카제인, 젖산칼슘, 프리모젤 등 부형제; 젤라틴, 아라비아고무, 에탄올, 한천가루, 초산프탈산셀룰로오스, 카르복시메칠셀룰로오스, 카르복시메칠셀룰로오스칼슘, 포도당, 정제수, 카제인나트륨, 글리세린, 스테아린산, 카르복시메칠셀룰로오스나트륨, 메칠셀룰로오스나트륨, 메칠셀룰로오스, 미결정셀룰로오스, 덱스트린, 히드록시셀룰로오스, 히드록시프로필스타치, 히드록시메칠셀룰로오스, 정제쉘락, 전분호, 히드록시프로필셀룰로오스, 히드록시프로필메칠셀룰로오스, 폴리비닐알코올, 폴리비닐피롤리돈 등의 결합제가 사용될 수 있으며, 히드록시프로필메칠셀룰로오스, 옥수수전분, 한천가루, 메칠셀룰로오스, 벤토나이트, 히드록시프로필스타치, 카르복시메칠셀룰로오스나트륨, 알긴산나트륨, 카르복시메칠셀룰로오스칼슘, 구연산칼슘, 라우릴황산나트륨, 무수규산, 1-히드록시프로필셀룰로오스, 덱스트란, 이온교환수지, 초산폴리비닐, 포름알데히드처리 카제인 및 젤라틴, 알긴산, 아밀로오스, 구아르고무(Guar gum), 중조, 폴리비닐피롤리돈, 인산칼슘, 겔화전분, 아라비아고무, 아밀로펙틴, 펙틴, 폴리인산나트륨, 에칠셀룰로오스, 백당, 규산마그네슘알루미늄, 디-소르비톨액, 경질무수규산 등 붕해제; 스테아린산칼슘, 스테아린산마그네슘, 스테아린산, 수소화식물유(Hydrogenated vegetable oil), 탈크, 석송자, 카올린, 바셀린, 스테아린산나트륨, 카카오지, 살리실산나트륨, 살리실산마그네슘, 폴리에칠렌글리콜 4000, 폴리에칠렌글리콜 6000, 유동파라핀, 수소첨가대두유(Lubri wax), 스테아린산알루미늄, 스테아린산아연, 라우릴황산나트륨, 산화마그네슘, 마크로골(Macrogol), 합성규산알루미늄, 무수규산, 고급지방산, 고급알코올, 실리콘유, 파라핀유, 폴리에칠렌글리콜지방산에테르, 전분, 염화나트륨, 초산나트륨, 올레인산나트륨, dl-로이신, 경질무수규산 등의 활택제;가 사용될 수 있다.Corn starch, potato starch, wheat starch, lactose, sucrose, glucose, fructose, di-mannitol, precipitated calcium carbonate, synthetic aluminum silicate, phosphoric acid as additives for tablets, powders, granules, capsules, pills, and troches according to the present invention Calcium monohydrogen, calcium sulfate, sodium chloride, sodium bicarbonate, purified lanolin, microcrystalline cellulose, dextrin, sodium alginate, methylcellulose, sodium carboxymethylcellulose, kaolin, urea, colloidal silica gel, hydroxypropyl starch, hydroxypropylmethyl Excipients such as cellulose (HPMC) 1928, HPMC 2208, HPMC 2906, HPMC 2910, propylene glycol, casein, calcium lactate, Primogel; Gelatin, gum arabic, ethanol, agar powder, cellulose phthalate acetate, carboxymethyl cellulose, calcium carboxymethyl cellulose, glucose, purified water, sodium caseinate, glycerin, stearic acid, sodium carboxymethyl cellulose, sodium methyl cellulose, methyl cellulose, microcrystalline cellulose, dextrin Binders such as hydroxycellulose, hydroxypropyl starch, hydroxymethylcellulose, purified shellac, starch arc, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, and polyvinylpyrrolidone may be used, Hydroxypropyl Methyl Cellulose, Corn Starch, Agar Powder, Methyl Cellulose, Bentonite, Hydroxypropyl Starch, Sodium Carboxymethyl Cellulose, Sodium Alginate, Calcium Carboxymethyl Cellulose, Calcium Citrate, Sodium Lauryl Sulfate, Silicic Anhydride, 1-Hydroxy Propyl cellulose, dextran, ion exchange resin, polyvinyl acetate, formaldehyde-treated casein and gelatin, alginic acid, amylose, guar gum, sodium bicarbonate, polyvinylpyrrolidone, calcium phosphate, gelled starch, gum arabic, disintegrants such as amylopectin, pectin, sodium polyphosphate, ethyl cellulose, white sugar, magnesium aluminum silicate, di-sorbitol solution, and light anhydrous silicic acid; Calcium stearate, magnesium stearate, stearic acid, hydrogenated vegetable oil, talc, lycopod, kaolin, petrolatum, sodium stearate, cacao butter, sodium salicylate, magnesium salicylate, polyethylene glycol 4000, polyethylene glycol 6000, liquid paraffin, hydrogenated soybean oil (Lubri wax), aluminum stearate, zinc stearate, sodium lauryl sulfate, magnesium oxide, macrogol, synthetic aluminum silicate, silicic anhydride, higher fatty acid, higher alcohol, silicone oil, paraffin oil, polyethylene glycol fatty acid ether, starch, A lubricant such as sodium chloride, sodium acetate, sodium oleate, dl-leucine, light anhydrous silicic acid; may be used.
본 발명에 따른 액제의 첨가제로는 물, 묽은 염산, 묽은 황산, 구연산나트륨, 모노스테아린산슈크로스류, 폴리옥시에칠렌소르비톨지방산에스텔류(트윈에스텔), 폴리옥시에칠렌모노알킬에텔류, 라놀린에텔류, 라놀린에스텔류, 초산, 염산, 암모니아수, 탄산암모늄, 수산화칼륨, 수산화나트륨, 프롤아민, 폴리비닐피롤리돈, 에칠셀룰로오스, 카르복시메칠셀룰로오스나트륨 등이 사용될 수 있다.Additives for the liquid formulation according to the present invention include water, dilute hydrochloric acid, dilute sulfuric acid, sodium citrate, sucrose monostearate, polyoxyethylene sorbitol fatty acid esters (tween esters), polyoxyethylene monoalkyl ethers, lanolin ethers, Lanolin esters, acetic acid, hydrochloric acid, aqueous ammonia, ammonium carbonate, potassium hydroxide, sodium hydroxide, prolamine, polyvinylpyrrolidone, ethyl cellulose, sodium carboxymethyl cellulose, and the like may be used.
본 발명에 따른 시럽제에는 백당의 용액, 다른 당류 혹은 감미제 등이 사용될 수 있으며, 필요에 따라 방향제, 착색제, 보존제, 안정제, 현탁화제, 유화제, 점조제 등이 사용될 수 있다.In the syrup according to the present invention, a solution of white sugar, other sugars, or a sweetener may be used, and aromatics, coloring agents, preservatives, stabilizers, suspending agents, emulsifiers, thickeners, etc. may be used as necessary.
본 발명에 따른 유제에는 정제수가 사용될 수 있으며, 필요에 따라 유화제, 보존제, 안정제, 방향제 등이 사용될 수 있다.Purified water may be used in the emulsion according to the present invention, and emulsifiers, preservatives, stabilizers, fragrances, etc. may be used as needed.
본 발명에 따른 현탁제에는 아카시아, 트라가칸타, 메칠셀룰로오스, 카르복시메칠셀룰로오스, 카르복시메칠셀룰로오스나트륨, 미결정셀룰로오스, 알긴산나트륨, 히드록시프로필메칠셀룰로오스, HPMC 1828, HPMC 2906, HPMC 2910 등 현탁화제가 사용될 수 있으며, 필요에 따라 계면활성제, 보존제, 안정제, 착색제, 방향제가 사용될 수 있다.Acacia, tragacantha, methylcellulose, carboxymethylcellulose, carboxymethylcellulose sodium, microcrystalline cellulose, sodium alginate, hydroxypropylmethylcellulose, HPMC 1828, HPMC 2906, HPMC 2910, etc. and, if necessary, surfactants, preservatives, stabilizers, colorants, and fragrances may be used.
본 발명에 따른 주사제에는 주사용 증류수, 0.9%염화나트륨주사액, 링겔주사액, 덱스트로스주사액, 덱스트로스+염화나트륨주사액, 피이지(PEG), 락테이티드 링겔주사액, 에탄올, 프로필렌글리콜, 비휘발성유-참기름, 면실유, 낙화생유, 콩기름, 옥수수기름, 올레인산에칠, 미리스트산 이소프로필, 안식향산벤젠과 같은 용제; 안식향산나트륨, 살리실산나트륨, 초산나트륨, 요소, 우레탄, 모노에칠아세트아마이드, 부타졸리딘, 프로필렌글리콜, 트윈류, 니정틴산아미드, 헥사민, 디메칠아세트아마이드와 같은 용해보조제; 약산 및 그 염(초산과 초산나트륨), 약염기 및 그 염(암모니아 및 초산암모니움), 유기화합물, 단백질, 알부민, 펩톤, 검류와 같은 완충제; 염화나트륨과 같은 등장화제; 중아황산나트륨(NaHSO3) 이산화탄소가스, 메타중아황산나트륨(Na2S2O5), 아황산나트륨(Na2SO3), 질소가스(N2), 에칠렌디아민테트라초산과 같은 안정제; 소디움비설파이드 0.1%, 소디움포름알데히드 설폭실레이트, 치오우레아, 에칠렌디아민테트라초산디나트륨, 아세톤소디움비설파이트와 같은 황산화제; 벤질알코올, 클로로부탄올, 염산프로카인, 포도당, 글루콘산칼슘과 같은 무통화제; 시엠시나트륨, 알긴산나트륨, 트윈 80, 모노스테아린산알루미늄과 같은 현탁화제를 포함할 수 있다.Injections according to the present invention include distilled water for injection, 0.9% sodium chloride injection, IV injection, dextrose injection, dextrose + sodium chloride injection, PEG, lactated IV injection, ethanol, propylene glycol, non-volatile oil-sesame oil , solvents such as cottonseed oil, peanut oil, soybean oil, corn oil, ethyl oleate, isopropyl myristate, and benzene benzoate; solubilizing agents such as sodium benzoate, sodium salicylate, sodium acetate, urea, urethane, monoethylacetamide, butazolidine, propylene glycol, twins, nijuntinamide, hexamine, and dimethylacetamide; buffers such as weak acids and their salts (acetic acid and sodium acetate), weak bases and their salts (ammonia and ammonium acetate), organic compounds, proteins, albumin, peptone, and gums; tonicity agents such as sodium chloride; Stabilizers such as sodium bisulfite (NaHSO 3 ) carbon dioxide gas, sodium metabisulfite (Na 2 S 2 O 5 ), sodium sulfite (Na 2 SO 3 ), nitrogen gas (N 2 ), ethylenediaminetetraacetic acid; Sulfating agents such as sodium bisulfide 0.1%, sodium formaldehyde sulfoxylate, thiourea, ethylenediamine disodium tetraacetate, acetone sodium bisulfite; analgesics such as benzyl alcohol, chlorobutanol, procaine hydrochloride, glucose, and calcium gluconate; Suspending agents such as Siemesis sodium, sodium alginate,
본 발명에 따른 좌제에는 카카오지, 라놀린, 위텝솔, 폴리에틸렌글리콜, 글리세로젤라틴, 메칠셀룰로오스, 카르복시메칠셀룰로오스, 스테아린산과 올레인산의 혼합물, 수바날(Subanal), 면실유, 낙화생유, 야자유, 카카오버터+콜레스테롤, 레시틴, 라네트왁스, 모노스테아린산글리세롤, 트윈 또는 스판, 임하우젠(Imhausen), 모놀렌(모노스테아린산프로필렌글리콜), 글리세린, 아뎁스솔리두스(Adeps solidus), 부티룸 태고-G(Buytyrum Tego-G), 세베스파마 16(Cebes Pharma 16), 헥사라이드베이스 95, 코토마(Cotomar), 히드록코테 SP, S-70-XXA, S-70-XX75(S-70-XX95), 히드록코테(Hydrokote) 25, 히드록코테 711, 이드로포스탈 (Idropostal), 마사에스트라리움(Massa estrarium, A, AS, B, C, D, E, I, T), 마사-MF, 마수폴, 마수폴-15, 네오수포스탈-엔, 파라마운드-B, 수포시로(OSI, OSIX, A, B, C, D, H, L), 좌제기제 IV 타입(AB, B, A, BC, BBG, E, BGF, C, D, 299), 수포스탈(N, Es), 웨코비(W, R, S, M ,Fs), 테제스터 트리글리세라이드 기제(TG-95, MA, 57)와 같은 기제가 사용될 수 있다.The suppository according to the present invention includes cacao butter, lanolin, witapsol, polyethylene glycol, glycerogelatin, methylcellulose, carboxymethylcellulose, a mixture of stearic acid and oleic acid, subanal, cottonseed oil, peanut oil, palm oil, cacao butter + Cholesterol, Lecithin, Lannet Wax, Glycerol Monostearate, Tween or Span, Imhausen, Monolen (Propylene Glycol Monostearate), Glycerin, Adeps Solidus, Buytyrum Tego-G -G), Cebes Pharma 16, Hexalide Base 95, Cotomar, Hydroxycote SP, S-70-XXA, S-70-XX75 (S-70-XX95),
경구 투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations contain at least one excipient, for example, starch, calcium carbonate, sucrose, etc. ) or by mixing lactose and gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
경구 투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜 (propylene glycol), 폴리에칠렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. Liquid preparations for oral administration include suspensions, solutions for oral administration, emulsions, syrups, etc. 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. there is. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.
본 발명에 따른 약학적 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명에 있어서, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type of patient's disease, severity, activity of the drug, It may be determined according to factors including sensitivity to the drug, administration time, route of administration and excretion rate, duration of treatment, drugs used concurrently, and other factors well known in the medical field.
본 발명에 따른 약학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 본 발명이 속하는 기술분야에 통상의 기술자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple times. Considering all of the above factors, it is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by a person skilled in the art to which the present invention belongs.
본 발명의 약학적 조성물은 개체에게 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구 복용, 피하 주사, 복강 투여, 정맥 주사, 근육 주사, 척수 주위 공간(경막내) 주사, 설하 투여, 볼점막 투여, 직장 내 삽입, 질 내 삽입, 안구 투여, 귀 투여, 비강 투여, 흡입, 입 또는 코를 통한 분무, 피부 투여, 경피 투여 등에 따라 투여될 수 있다.The pharmaceutical composition of the present invention can be administered to a subject by various routes. All modes of administration can be envisaged, eg oral administration, subcutaneous injection, intraperitoneal administration, intravenous injection, intramuscular injection, paraspinal space (intrathecal) injection, sublingual administration, buccal administration, intrarectal insertion, vaginal It can be administered by intraoral insertion, ocular administration, otic administration, nasal administration, inhalation, spraying through the mouth or nose, dermal administration, transdermal administration, and the like.
본 발명의 약학적 조성물은 치료할 질환, 투여 경로, 환자의 연령, 성별, 체중 및 질환의 중등도 등의 여러 관련 인자와 함께 활성성분인 약물의 종류에 따라 결정된다.The pharmaceutical composition of the present invention is determined according to the type of drug as an active ingredient together with various related factors such as the disease to be treated, the route of administration, the age, sex, weight and severity of the disease of the patient.
본 발명에서 "개체"란 질병의 치료를 필요로 하는 대상을 의미하고, 보다 구체적으로는 인간 또는 비-인간인 영장류, 생쥐 (mouse), 쥐 (rat), 개, 고양이, 말, 및 소 등의 포유류를 의미한다.In the present invention, "subject" means a subject in need of treatment of a disease, and more specifically, a human or non-human primate, mouse, rat, dog, cat, horse, cow, etc. of mammals.
본 발명에서 “투여”란 임의의 적절한 방법으로 개체에게 소정의 본 발명의 조성물을 제공하는 것을 의미한다.In the present invention, "administration" means providing a given composition of the present invention to a subject by any suitable method.
본 발명에서 "예방"이란 목적하는 질환의 발병을 억제하거나 지연시키는 모든 행위를 의미하고, "치료"란 본 발명에 따른 약학적 조성물의 투여에 의해 목적하는 질환과 그에 따른 대사 이상 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미하며, “개선"이란 본 발명에 따른 조성물의 투여에 의해 목적하는 질환과 관련된 파라미터, 예를 들면 증상의 정도를 감소시키는 모든 행위를 의미한다. In the present invention, "prevention" refers to any action that suppresses or delays the onset of a desired disease, and "treatment" means that a desired disease and its associated metabolic abnormalities are improved or treated by administration of the pharmaceutical composition according to the present invention. All actions that are beneficially altered are meant, and "improvement" means any action that reduces a parameter related to a desired disease, for example, the severity of a symptom, by administration of the composition according to the present invention.
또한, 살오징어 추출물을 유효성분으로 포함하는, 만성 폐쇄성 폐질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, it provides a health functional food composition for preventing or improving chronic obstructive pulmonary disease, comprising a cuttlefish extract as an active ingredient.
본 발명의 살오징어 추출물을 식품 첨가물로 사용할 경우, 상기 살오징어 추출물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시 본 발명의 살오징어 추출물은 원료에 대하여 15 중량% 이하, 또는 10 중량% 이하의 양으로 첨가될 수 있다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.When the squid extract of the present invention is used as a food additive, the squid extract may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment). In general, when preparing food or beverage, the squid extract of the present invention may be added in an amount of 15% by weight or less, or 10% by weight or less based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene 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.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.There is no particular limitation on the type of food. Examples of foods to which the above substances can be added include meat, sausages, bread, chocolates, candies, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice creams, various soups, beverages, tea, drinks, There are alcoholic beverages and vitamin complexes, and includes all health functional foods in a conventional sense.
본 발명에 따른 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당 및 과당과 같은 모노사카라이드, 말토오스 및 수크로오스와 같은 디사카라이드, 덱스트린 및 시클로덱스트린과 같은 폴리사카라이드, 및 자일리톨, 소르비톨 및 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 mL당 일반적으로 약 0.01-0.20 g, 또는 약 0.04-0.10 g 이다.The health beverage composition according to the present invention may contain various flavoring agents or natural carbohydrates as additional components, like conventional beverages. The aforementioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrins and cyclodextrins, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame may be used. The proportion of the natural carbohydrate is generally about 0.01-0.20 g, or about 0.04-0.10 g per 100 mL of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 조성물은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0.01-0.20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the composition of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, A carbonation agent used in carbonated beverages and the like may be contained. In addition, the composition of the present invention may contain fruit flesh for preparing natural fruit juice, fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The ratio of these additives is not critical, but is generally selected in the range of 0.01-0.20 parts by weight per 100 parts by weight of the composition of the present invention.
이하, 본 발명의 이해를 돕기 위하여 하기 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, the following examples are presented to aid understanding of the present invention. However, the following examples are provided to more easily understand the present invention, and the content of the present invention is not limited by the following examples.
[실시예][Example]
실시예 1. 살오징어 추출물의 제조Example 1. Preparation of squid extract
살오징어(Todarodes pacificus) 다리 시료(1.5kg)를 3 L의 20% 에탄올에 침지한 후, 실온에서 3시간 간격으로 2회 추출하였다. 얻은 추출물을 부분 농축 후, 동결건조하여 농축물을 얻었다. 살오징어 추출물을 2-86이라고 명하였다.Cuttlefish ( Todarodes pacificus ) Leg samples (1.5 kg) were immersed in 3 L of 20% ethanol, and then extracted twice at room temperature at 3-hour intervals. After partially concentrating the obtained extract, it was lyophilized to obtain a concentrate. The squid extract was named 2-86.
실시예 2. 살오징어 추출물의 항염증 효과 확인Example 2. Confirmation of anti-inflammatory effect of squid extract
마우스 유래 대식세포인 RAW 264.7 세포에 살오징어 추출물(2-86)과 LPS(lipopolysaccharide)를 20시간 동안 처리한 뒤, 배지 중에 유리된 NO를 아질산염(nitrite) 농도로 환산하여 평가하였다. 구체적으로, RAW 264.7 세포를 24-웰 플레이트의 각 웰에 2.5x105개로 첨가한 뒤, 1일 후에 살오징어 추출물을 250, 500, 1000 μg/mL의 농도로 LPS 1 μg/ml와 함께 처리하고 37℃, 5% CO2 조건인 세포 배양기에서 20시간 동안 배양하였다. 배양 후, 배지 50 μL를 96-웰 플레이트에 넣고 5% 인산 용액에 제조한 1% 설파닐아마이드 용액을 첨가한 후, 실온에서 10분간 배양한 뒤, 0.1% N-1-나프틸에틸렌디아민 디하이드로염화물 용액 50 μL을 처리하고, 발색 정도를 정량적으로 측정하기 위해 540 nm에서 흡광도를 측정하였다. 여러 농도를 희석한 아질산나트륨 용액을 같은 조건으로 반응시킨 후, 검량선을 작성하여 배지 중의 NO를 아질산염 농도로 환산하였다. 그 결과는 도 1에 나타내었다.Mouse-derived macrophage RAW 264.7 cells were treated with squid extract (2-86) and LPS (lipopolysaccharide) for 20 hours, and NO released in the medium was evaluated in terms of nitrite concentration. Specifically, RAW 264.7 cells were added to each well of a 24-well plate at 2.5x10 5 cells, and after 1 day, the squid extract was treated with LPS 1 μg/ml at concentrations of 250, 500, and 1000 μg/mL, 37 ℃, 5% CO 2 It was cultured for 20 hours in a cell incubator. After incubation, 50 μL of the medium was placed in a 96-well plate, 1% sulfanilamide solution prepared in 5% phosphoric acid solution was added, and after incubation at room temperature for 10 minutes, 0.1% N-1-naphthylethylenediamine diamine was added. 50 μL of the hydrochloride solution was treated, and absorbance was measured at 540 nm to quantitatively measure the degree of color development. After reacting with sodium nitrite solutions diluted with various concentrations under the same conditions, a calibration curve was prepared and NO in the medium was converted into nitrite concentration. The results are shown in Figure 1.
도 1에 나타난 바와 같이, 살오징어 추출물은 LPS에 의한 NO 생성을 농도 의존적으로 억제하였다. 이는 살오징어 추출물이 항염증 효과가 있다는 것을 의미한다. As shown in Figure 1, the cuttlefish extract inhibited NO production by LPS in a concentration-dependent manner. This means that the cuttlefish extract has an anti-inflammatory effect.
실시예 3. 살오징어 추출물의 항산화 효과 확인Example 3. Confirmation of antioxidant effect of squid extract
마우스 유래 대식세포인 RAW 264.7 세포에 살오징어 추출물과 LPS(lipopolysaccharide)를 20시간 동안 처리한 뒤, 세포 내 ROS를 H2DCF-DA를 이용하여 측정하였다. 구체적으로, RAW 264.7 세포를 바닥이 투명한 검정색 96-웰 플레이트의 각 웰에 5x104개로 첨가한 뒤, 1일 후에 살오징어 추출물을 250, 500, 1000 μg/mL의 농도로 LPS 1 μg/mL와 함께 처리하고 37℃, 5% CO2 조건인 세포 배양기에서 20시간 동안 배양하였다. 배양 후, 세포에 20 μM H2DCF-DA 용액을 처리한 뒤 37℃, 5% CO2 조건인 세포 배양기에서 1시간 동안 배양한 다음, 여기 파장 485 nm 및 방출 파장 535 nm에서 형광을 측정하였다. 그 결과는 도 2에 나타내었다.Mouse-derived macrophage RAW 264.7 cells were treated with squid extract and LPS (lipopolysaccharide) for 20 hours, and intracellular ROS was measured using H 2 DCF-DA. Specifically, RAW 264.7 cells were added to each well of a 96-well black 96-well plate with a clear bottom at 5x10 cells, and after 1 day , squid extracts were added with 1 μg/mL of LPS at concentrations of 250, 500, and 1000 μg/mL. They were treated together and cultured for 20 hours in a cell incubator at 37°C and 5% CO 2 conditions. After incubation, the cells were treated with a 20 μM H 2 DCF-DA solution and incubated for 1 hour in a cell incubator at 37° C. under 5% CO 2 conditions, and fluorescence was measured at an excitation wavelength of 485 nm and an emission wavelength of 535 nm. . The results are shown in Figure 2.
도 2에 나타난 바와 같이, 살오징어 추출물은 LPS에 의한 ROS 생성을 농도 의존적으로 억제하였다. 이는 살오징어 추출물이 항산화 효과가 있다는 것을 의미한다. As shown in Figure 2, the cuttlefish extract inhibited ROS production by LPS in a concentration-dependent manner. This means that the cuttlefish extract has an antioxidant effect.
실시예 4. 살오징어 추출물의 정상 세포에 대한 독성 확인Example 4. Confirmation of toxicity of squid extract to normal cells
실시예 2 또는 3의 NO 또는 ROS 생성 억제 활성 평가 후, 배지를 회수하고 부착된 세포를 100% 메탄올로 실온에서 30분간 고정하였다. 고정 후 메탄올을 제거하고 실온 중에서 건조한 뒤, 0.025% 크리스탈 바이올렛 용액으로 고정된 세포를 실온에서 1시간 동안 염색하였다. 크리스탈 바이올렛 용액을 제거하고 수돗물로 염색된 세포를 여러 번 세척하여 여분의 염색액을 제거한 뒤 건조하였다. 그 후, 염색된 세포를 1% SDS(sodium dodecyl sulfate) 용액으로 녹이고 570 nm에서 흡광도를 측정하였다. 세포 생존율은 대조군의 흡광도에 대한 실험군의 흡광도의 백분율로 계산하였다. 그 결과는 도 3에 나타내었다.After evaluating the NO or ROS production inhibitory activity of Example 2 or 3, the medium was recovered and the attached cells were fixed with 100% methanol at room temperature for 30 minutes. After fixation, methanol was removed, and after drying at room temperature, the fixed cells were stained with 0.025% crystal violet solution for 1 hour at room temperature. After removing the crystal violet solution, the stained cells were washed several times with tap water to remove excess staining solution and dried. Then, the stained cells were dissolved in a 1% SDS (sodium dodecyl sulfate) solution and absorbance was measured at 570 nm. Cell viability was calculated as a percentage of the absorbance of the experimental group to the absorbance of the control group. The results are shown in Figure 3.
도 3에 나타난 바와 같이, 살오징어 추출물은 정상 세포의 생존율에는 영향을 미치지 않으며, 이를 통하여 살오징어 추출물은 세포 독성이 낮은 것을 확인하였다.As shown in FIG. 3, the squid extract did not affect the viability of normal cells, and through this, it was confirmed that the squid extract had low cytotoxicity.
실시예 5. 살오징어 추출물의 염증 관련 사이토카인 및 염증성 효소 발현 억제 효과 확인Example 5. Confirmation of the effect of suppressing the expression of inflammation-related cytokines and inflammatory enzymes of the squid extract
마우스 유래 대식세포인 RAW 264.7에 살오징어 추출물 500 μg/mL와 LPS(lipopolysaccharide) 1 μg/mL 또는 엘라스타제(elastase) 0.01 U/mL를 처리하고, 37℃, 5% CO2 조건인 세포 배양기에서 20시간 동안 배양하였다. 배양 후, 세포를 easy-BLUE 용액(Intron)으로 분해한 뒤, 페놀-클로로폼(phenol-chloroform)법을 이용하여 세포 중 RNA를 분리하였다. 그 후, 260 nm, 280 nm, 230 nm에서 흡광도를 측정하여 RNA의 양과 순도를 결정한 뒤, 1-2 μg의 RNA를 first-strand cDNA 합성 키트를 이용하여 cDNA로 변환시키고, 1/10 내지 1/50로 희석된 cDNA를 SYBR Green I dye, dNTP 용액 및 유전자 선택적 프라이머가 혼합된 nTaq-HOT DNA 폴리머라제를 이용하여 증폭하였다. cDNA의 증폭은 95℃에서 20분간의 전처리 후, 95℃에서 15초 및 60℃에서 30초간 배양하는 조건을 총 45회 반복하여 진행하였고, 증폭된 cDNA에 SYBR Green 염색약의 혼입의 선택성을 검증하기 위한 용융 곡선 분석(melting curve analysis)을 진행하였다. cDNA의 증폭을 실시간으로 모니터링하여 CT(cycle threshold) 값을 결정한 뒤, 18S rRNA (Rn18s) 유전자의 증폭 정도를 참고하여 2-△△Ct 법으로 살오징어 추출물에 의한 유전자 발현 변화를 확인하였다. 그 결과는 도 4 및 5에 나타내었다. 또한, 실험에 사용한 프라이머의 서열을 하기 표 1에 나타내었다.RAW 264.7 mouse-derived macrophage cells were treated with 500 μg/mL of squid extract, 1 μg/mL of LPS (lipopolysaccharide) or 0.01 U/mL of elastase, and a cell incubator under 37°C and 5% CO 2 conditions. incubated for 20 hours. After culturing, the cells were disassembled with an easy-BLUE solution (Intron), and RNA was isolated from the cells using a phenol-chloroform method. Then, the amount and purity of RNA were determined by measuring absorbance at 260 nm, 280 nm, and 230 nm, and then 1-2 μg of RNA was converted into cDNA using a first-strand cDNA synthesis kit, and 1/10 to 1 /50 diluted cDNA was amplified using nTaq-HOT DNA polymerase mixed with SYBR Green I dye, dNTP solution, and gene-selective primers. Amplification of cDNA was carried out by repeating the conditions of pretreatment at 95 ° C for 20 minutes, incubation at 95 ° C for 15 seconds and at 60 ° C for 30 seconds in total 45 times, and to verify the selectivity of SYBR Green dye incorporation into amplified cDNA. A melting curve analysis was performed for After determining the CT (cycle threshold) value by monitoring the amplification of cDNA in real time, the gene expression change by the cuttlefish extract was confirmed by the 2 -ΔΔCt method with reference to the amplification level of the 18S rRNA (Rn18s) gene. The results are shown in Figures 4 and 5. In addition, the sequences of the primers used in the experiment are shown in Table 1 below.
도 4에 나타난 바와 같이, 살오징어 추출물은 LPS에 의해 유도된 염증성 효소 Nos2와 염증성 사이토카인 TNF-α의 발현을 유의적으로 억제하였다.As shown in Figure 4, the cuttlefish extract significantly suppressed the expression of the inflammatory enzyme Nos2 and the inflammatory cytokine TNF-α induced by LPS.
도 5에 나타난 바와 같이, 살오징어 추출물은 엘라스타제에 의해 유도된 염증성 사이토카인 IL-1β 및 IL-6의 발현을 유의적으로 억제하였다.As shown in Figure 5, the squid extract significantly suppressed the expression of the inflammatory cytokines IL-1β and IL-6 induced by elastase.
실시예 6. 살오징어 추출물의 폐기종 억제에 미치는 영향 확인Example 6. Confirmation of effect of squid extract on suppression of emphysema
6.1. 폐 기능의 확인6.1. Confirmation of lung function
살오징어 추출물이 생체 내에서 폐기종(emphysema) 억제에 미치는 효과를 폐 기능을 통해 확인하였다. 구체적으로, FVB 마우스에 살오징어 추출물 500 mg/kg을 1회 경구투여한 뒤 돼지 췌장 유래 엘라스타제(PPE; porcine pancreatic elastase, 폐조직 파괴를 유발하는 단백질 분해 효소) 0.5 U을 기도로 1회 투여하였다. 그리고 다시 살오징어 추출물을 주 6회로 3주간 투여하였다. 이후 폐 기능을 확인하기 위하여, 마우스의 폐 유순도(compliance)와 폐 탄성도(tissue elastance, 횡경막의 근육 수축작용으로 호흡하는 능력)를 FlexiVent RM을 이용하여 측정하였다. 그 결과를 도 6에 나타내었다.The effect of squid extract on suppression of emphysema in vivo was confirmed through lung function. Specifically, after oral administration of 500 mg/kg of squid extract to FVB mice once, 0.5 U of porcine pancreatic elastase (PPE; a proteolytic enzyme that causes lung tissue destruction) was administered once through the airway. administered. Then, the squid extract was administered 6 times a week for 3 weeks. Then, in order to confirm lung function, lung compliance and lung elasticity (tissue elastance, ability to breathe by muscle contraction of the diaphragm) of the mice were measured using the FlexiVent RM. The results are shown in FIG. 6 .
도 6에 나타난 바와 같이, PPE만 처리한 경우에는 폐의 유순도는 증가되고, 폐 탄성도는 감소되어 폐의 기능이 현저히 감소되나, PPE와 함께 살오징어 추출물을 투여한 실험 군에서는 폐 유순도는 다시 감소되고, 폐 탄성도은 다시 증가되어 폐 기능이 회복된 것을 확인하였다. 또한, 살오징어 추출물만을 투여한 실험 군에서는 폐 유순도, 폐 탄성도가 대조군과 비슷한 수준임을 확인하였다. 상기 결과들을 통하여, 살오징어 추출물이 폐기종 억제 효과가 있음을 확인할 수 있었다.As shown in FIG. 6, when only PPE was treated, lung compliance increased and lung elasticity decreased, resulting in a marked decrease in lung function. decreased, and lung elasticity increased again, confirming that lung function was restored. In addition, it was confirmed that lung compliance and lung elasticity were similar to those of the control group in the experimental group administered with only the squid extract. Through the above results, it was confirmed that the squid extract had an emphysema inhibitory effect.
6.2. H&E 염색6.2. H&E staining
살오징어 추출물 투여가 폐 조직의 손상에 미치는 영향을 확인하기 위하여, 실시예 6.1과 동일한 방법으로 처리된 마우스의 폐를 분리하고, 분리된 폐를 10% 포르말린(formalin)을 사용하여 24시간 동안 고정시킨 후에 파라핀을 이용하여 파라핀 블록을 제작하였다. 제작된 파라핀 블록은 4 μm의 두께로 자른 후에 실란이 코팅된 슬라이드(silane coating slide)에 부착시키고 건조시켰다. 건조된 슬라이드는 65℃ 건조오븐(dry oven)에 넣어 16시간 동안 탈파라핀화를 진행하고, 자일렌(xylene) 용액에 5분씩 2회 동안 담가 세척하였다. 그리고 고정된 폐 조직 절편을 100%, 95%, 70% 알코올(alcohol)로 탈파라핀화 및 수화시킨 다음, 증류수로 세척하였다. 이후, Harris hematoxylin 용액을 이용하여 1분 30초 동안 염색시키고, 1 % HCl alcohol 용액과 암모니아(ammonia)로 침적시켜 세척한 후에 에오신(eosin) 용액을 이용하여 30초간 염색하였다. 그리고 다시 95% 에탄올과 100% 에탄올을 이용하여 순차적으로 탈수시킨 후, 자일렌 용액을 이용하여 최종 세척한 후에 봉입하여 현미경으로 관찰하고 사진을 획득하였다. 그 결과는 도 7에 나타내었다.In order to confirm the effect of squid extract administration on damage to lung tissue, the lungs of mice treated in the same manner as in Example 6.1 were isolated, and the isolated lungs were fixed for 24 hours using 10% formalin After that, a paraffin block was prepared using paraffin. After cutting the fabricated paraffin block to a thickness of 4 μm, it was attached to a silane coated slide and dried. The dried slides were put in a dry oven at 65° C. to deparaffinize for 16 hours, and washed by immersing them in a xylene solution twice for 5 minutes each. Then, the fixed lung tissue sections were deparaffinized and hydrated with 100%, 95%, and 70% alcohol, and washed with distilled water. Then, it was stained for 1 minute and 30 seconds using a Harris hematoxylin solution, washed by immersion with a 1% HCl alcohol solution and ammonia, and then stained for 30 seconds using an eosin solution. Then, after sequential dehydration using 95% ethanol and 100% ethanol, final washing using a xylene solution was carried out, and the cells were sealed, observed under a microscope, and photographs were obtained. The results are shown in FIG. 7 .
도 7에 나타난 바와 같이, PPE만 투여한 실험군의 폐 조직은 붕괴되었지만, PPE와 함께 살오징어 추출물을 투여한 실험군의 경우에는 폐 조직의 손상이 감소된 것을 확인하였다.As shown in FIG. 7, the lung tissue of the experimental group administered only with PPE collapsed, but in the experimental group administered with the squid extract together with PPE, it was confirmed that damage to the lung tissue was reduced.
실시예 7. 살오징어 추출물의 폐기종 치료에 미치는 영향 확인Example 7. Confirmation of effect of squid extract on treatment of emphysema
7.1. 폐 기능의 확인7.1. Confirmation of lung function
살오징어 추출물이 생체 내에서 폐기종(emphysema) 치료에 미치는 효과를 폐 기능을 통해 확인하였다. 구체적으로, FVB 마우스에 돼지 췌장 유래 엘라스타제(PPE; porcine pancreatic elastase, 폐조직 파괴를 유발하는 단백질 분해 효소) 0.5 U을 기도로 1회 투여하고, 2주 후 동일한 용량으로 1회 더 투여하였다. 그 후, 살오징어 추출물 500 mg/kg을 주 6회로 2주간 투여하였다. 이후 폐 기능을 확인하기 위하여, 마우스의 폐 유순도(compliance)와 폐 탄성도(tissue elastance, 횡경막의 근육 수축작용으로 호흡하는 능력)를 FlexiVent RM을 이용하여 측정하였다. 그 결과를 도 8에 나타내었다.The effect of squid extract on the treatment of emphysema in vivo was confirmed through lung function. Specifically, porcine pancreatic elastase (PPE; porcine pancreatic elastase, a proteolytic enzyme that causes lung tissue destruction) was administered to FVB mice once through the airway, and 2 weeks later, the same dose was administered once more. . Thereafter, 500 mg/kg of squid extract was administered 6 times a week for 2 weeks. Then, in order to confirm lung function, lung compliance and lung elasticity (tissue elastance, ability to breathe by muscle contraction of the diaphragm) of the mice were measured using the FlexiVent RM. The results are shown in FIG. 8 .
도 8에 나타난 바와 같이, PPE만 처리한 경우에는 폐의 유순도는 증가되고, 폐 탄성도는 감소되어 폐의 기능이 현저히 감소되나, PPE와 함께 살오징어 추출물을 투여한 실험 군에서는 폐 유순도는 다시 감소되고, 폐 탄성도은 다시 증가되어 폐 기능이 회복된 것을 확인하였다. 상기 결과들을 통하여, 살오징어 추출물이 이미 생성된 폐기종에 대한 치료 효과가 있음을 확인할 수 있었다.As shown in FIG. 8, when only PPE was treated, lung compliance increased and lung elasticity decreased, resulting in a marked decrease in lung function. decreased, and lung elasticity increased again, confirming that lung function was restored. Through the above results, it was confirmed that the cuttlefish extract has a therapeutic effect on already formed emphysema.
7.2. H&E 염색7.2. H&E staining
실시예 6.2와 동일한 방법으로 실험을 하였다. 그 결과는 도 9에 나타내었다.Experiments were conducted in the same manner as in Example 6.2. The results are shown in FIG. 9 .
도 9에 나타난 바와 같이, PPE만 투여한 실험군의 폐 조직은 심각하게 붕괴되었지만, PPE와 함께 살오징어 추출물을 투여한 실험군의 경우에는 폐 조직의 손상이 현저하게 감소된 것을 확인하였다.As shown in FIG. 9, the lung tissue of the experimental group administered only with PPE was severely disintegrated, but in the experimental group administered with the squid extract together with PPE, it was confirmed that the damage to the lung tissue was significantly reduced.
상기 결과들을 통하여, 본 발명의 살오징어 추출물을 유효성분으로 포함하는 조성물은 PPE를 투여한 폐기종 동물 모델의 폐 손상 및 파괴를 억제하고, 염증 반응을 효과적으로 감소키는 바, 폐의 기능을 유지 및/또는 회복시키는 것을 확인하였다. 이를 통하여 살오징어 추출물을 만성 폐쇄성 폐질환의 예방 또는 치료용 조성물로써 사용 가능하다는 것을 확인할 수 있었다.Through the above results, the composition containing the cuttlefish extract of the present invention as an active ingredient inhibits lung damage and destruction in an emphysema animal model administered with PPE and effectively reduces inflammatory responses, thereby maintaining and maintaining lung function. / or confirmed to recover. Through this, it was confirmed that the squid extract can be used as a composition for preventing or treating chronic obstructive pulmonary disease.
상기 진술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.The description of the present invention described above is for illustrative purposes, and those skilled in the art can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. There will be. Therefore, the embodiments described above should be understood as illustrative in all respects and not limiting.
<110> Seoul National University R&DB Foundation Republic of Korea(National Fisheries Research and Development Institute) <120> Phamaceutical composition for preventing or treating chronic obstructive pulmonary disease comprising Todarodes pacificus extract as an active ingredient <130> MP21-175 <160> 10 <170> KoPatentIn 3.0 <210> 1 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Nos2_F <400> 1 cagctgggct gtacaaacct t 21 <210> 2 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Nos2_R <400> 2 cattggaagt gaagcgtttc g 21 <210> 3 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Il1b_F <400> 3 aacctgctgg tgtgtgacgt tc 22 <210> 4 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Il1b_R <400> 4 cagcacgagg cttttttgtt gt 22 <210> 5 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Il6_F <400> 5 ctgcaagtgc atcatcgttg tt 22 <210> 6 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Il6_R <400> 6 ccggagagga gacttcacag ag 22 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Tnf_F <400> 7 cagccgatgg gttgtacctt 20 <210> 8 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Tnf_R <400> 8 tgtgggtgag gagcacgtag t 21 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Rn18s_F <400> 9 ggaataatgg aataggaccg 20 <210> 10 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Rn18s_R <400> 10 tctgtcaatc ctgtccgtgt cc 22 <110> Seoul National University R&DB Foundation Republic of Korea (National Fisheries Research and Development Institute) <120> Phamaceutical composition for preventing or treating chronic obstructive pulmonary disease comprising Todarodes pacificus extract as an active ingredient <130> MP21-175 <160> 10 <170> KoPatentIn 3.0 <210> 1 <211> 21 <212> DNA <213> artificial sequence <220> <223> Nos2_F <400> 1 cagctgggct gtacaaacct t 21 <210> 2 <211> 21 <212> DNA <213> artificial sequence <220> <223> Nos2_R <400> 2 cattggaagt gaagcgtttc g 21 <210> 3 <211> 22 <212> DNA <213> artificial sequence <220> <223> Il1b_F <400> 3 aacctgctgg tgtgtgacgt tc 22 <210> 4 <211> 22 <212> DNA <213> artificial sequence <220> <223> Il1b_R <400> 4 cagcacgagg cttttttgtt gt 22 <210> 5 <211> 22 <212> DNA <213> artificial sequence <220> <223> Il6_F <400> 5 ctgcaagtgc atcatcgttg tt 22 <210> 6 <211> 22 <212> DNA <213> artificial sequence <220> <223> Il6_R <400> 6 ccggagagga gacttcacag ag 22 <210> 7 <211> 20 <212> DNA <213> artificial sequence <220> <223> Tnf_F <400> 7 cagccgatgg gttgtacctt 20 <210> 8 <211> 21 <212> DNA <213> artificial sequence <220> <223> Tnf_R <400> 8 tgtgggtgag gagcacgtag t 21 <210> 9 <211> 20 <212> DNA <213> artificial sequence <220> <223> Rn18s_F <400> 9 ggaataatgg aataggaccg 20 <210> 10 <211> 22 <212> DNA <213> artificial sequence <220> <223> Rn18s_R <400> 10 tctgtcaatc ctgtccgtgt cc 22
Claims (8)
A pharmaceutical composition for preventing or treating chronic obstructive pulmonary disease, comprising a squid extract as an active ingredient.
상기 만성 폐쇄성 폐질환은 폐기종(emphysema)인 것을 특징으로 하는, 만성 폐쇄성 폐질환의 예방 또는 치료용 약학적 조성물.
According to claim 1,
The chronic obstructive pulmonary disease is characterized in that emphysema (emphysema), a pharmaceutical composition for preventing or treating chronic obstructive pulmonary disease.
상기 살오징어 추출물은 하기 증상 중 하나 이상을 억제 또는 개선하는 것을 특징으로 하는, 만성 폐쇄성 폐질환의 예방 또는 치료용 약학적 조성물:
i) 폐 유순도의 증가; 및
ii) 폐 탄성도의 감소.
According to claim 1,
The squid extract is a pharmaceutical composition for preventing or treating chronic obstructive pulmonary disease, characterized in that suppressing or improving one or more of the following symptoms:
i) increase in lung compliance; and
ii) a decrease in lung elasticity.
상기 살오징어 추출물은 TNF-α, IL-1β, 및 IL-6으로 이루어지는 군으로부터 선택된 하나 이상의 염증성 사이토카인의 발현을 억제하는 것을 특징으로 하는, 만성 폐쇄성 폐질환의 예방 또는 치료용 약학적 조성물.
According to claim 1,
The squid extract is characterized by inhibiting the expression of one or more inflammatory cytokines selected from the group consisting of TNF-α, IL-1β, and IL-6, a pharmaceutical composition for preventing or treating chronic obstructive pulmonary disease.
상기 살오징어 추출물은 Nos2의 발현을 억제하는 것을 특징으로 하는, 만성 폐쇄성 폐질환의 예방 또는 치료용 약학적 조성물.
According to claim 1,
The cuttlefish extract is a pharmaceutical composition for preventing or treating chronic obstructive pulmonary disease, characterized in that inhibiting the expression of Nos2.
상기 살오징어 추출물은 물, C1 내지 C4의 알코올, 에틸아세테이트, 클로로포름, 헥산, 및 이들의 혼합용매로 이루어지는 군으로부터 선택된 하나 이상의 용매로 추출되는 것을 특징으로 하는, 만성 폐쇄성 폐질환의 예방 또는 치료용 약학적 조성물.
According to claim 1,
The squid extract is characterized in that it is extracted with one or more solvents selected from the group consisting of water, C 1 to C 4 alcohol, ethyl acetate, chloroform, hexane, and mixed solvents thereof, preventing chronic obstructive pulmonary disease or Therapeutic pharmaceutical composition.
상기 살오징어 추출물은 살오징어 다리 추출물인 것을 특징으로 하는, 만성 폐쇄성 폐질환의 예방 또는 치료용 약학적 조성물.
According to claim 1,
The squid extract is a pharmaceutical composition for preventing or treating chronic obstructive pulmonary disease, characterized in that the squid leg extract.
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