KR20200021739A - Composition comprising Viburnum carlesii extract for preventing, improving or treating respiratory disease - Google Patents
Composition comprising Viburnum carlesii extract for preventing, improving or treating respiratory disease Download PDFInfo
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- KR20200021739A KR20200021739A KR1020180097476A KR20180097476A KR20200021739A KR 20200021739 A KR20200021739 A KR 20200021739A KR 1020180097476 A KR1020180097476 A KR 1020180097476A KR 20180097476 A KR20180097476 A KR 20180097476A KR 20200021739 A KR20200021739 A KR 20200021739A
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- extract
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- preventing
- asthma
- respiratory diseases
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Abstract
Description
본 발명은 분꽃나무(Viburnum carlesii) 추출물을 포함하는 호흡기 질환 예방, 개선 또는 치료용 약학적 조성물 내지 건강기능식품 조성물에 대한 것이다.The present invention relates to a pharmaceutical composition or a nutraceutical composition for the prevention, improvement or treatment of respiratory diseases, including the extract of Viburnum carlesii.
호흡기 질환은 주로 폐 및 기도와 관련된 질환을 의미하며, 그 중 기도는 크게 점막과 기관지 평활근(bronchial smooth muscle)으로 이루어져 있다. 점막에는 많은 분비샘들이 존재하여 필요한 분비물들을 계속 분비하고 있으며 기관지 평활근이 수축하는 경우 기도가 좁아지게 된다. 호흡기 질환 중 천식, 만성기관지염, 폐기종 등 기도폐쇄와 관련있는 질병들의 발명기전에는 기관지 평활근이 중요한 역할을 하는 것으로 알려져 있다. Respiratory disease mainly refers to diseases related to the lungs and airways, and the airways are largely composed of mucous membranes and bronchial smooth muscles. There are many secretory glands in the mucosa that continue to secrete the necessary secretions, and when the bronchial smooth muscle contracts, the airways become narrow. Bronchial smooth muscle is known to play an important role in the invention of airway obstruction such as asthma, chronic bronchitis and emphysema among respiratory diseases.
기관지 평활근과 관련된 호흡기 질병들은 비가역적일 수 있는 기도개형, 기도폐쇄, 기도염증 및 기도과민성 등을 특징으로 한다. 기도개형(airway remodeling)은 기도의 구조적인 변화로 기도상피세포하 섬유화(subepirhelial fibrosis), 점액세포 증식(globlet cell hyperplasia), 근육섬유모세포(myofibroblast) 내지 평활근세포의 증가, 신생혈관 생성 등의 소견을 보이며, 비가역적인 기도폐쇄와 기도과민성을 야기한다. 이중 기관지 평활근세포의 증가는 기관지 평활근 세포의 비후, 증식 및 이주가 그 기전으로 예상되고 있으며, 기관지 평활근 세포의 분열 증가, 세포고사(apoptosis)의 감소, 간엽세포(mesenchymal cell)의 이주 및 기관지 평활근 세포로의 분화 증가 등이 원인일 수 있다. Respiratory diseases associated with bronchial smooth muscle are characterized by airway remodeling, airway obstruction, airway inflammation and airway hyperresponsiveness that may be irreversible. Airway remodeling is a structural change in the airways that results in subepithelial fibrosis, globult cell hyperplasia, myofibroblast to smooth muscle cells, and neovascularization. And cause irreversible airway obstruction and airway hypersensitivity. The increase of bronchial smooth muscle cells is expected to be the mechanism by which thickening, proliferation and migration of bronchial smooth muscle cells, increased division of bronchial smooth muscle cells, reduction of apoptosis, migration of mesenchymal cells and bronchial smooth muscle This may be due to increased differentiation into cells.
분꽃나무(Viburnum carlesii)는 연복초과 식물로서 한국이나 일본 대마도에 분포한다. 관상용으로 심으며 도시내의 공원수로도 이용되나, 그의 약학적 효능에 대하여는 알려진 바 없다. A branch of Viburnum carlesii is a lobster plant that is distributed in Korea and Japan. It is planted for ornamental purposes and used as a park water in the city, but its pharmaceutical efficacy is unknown.
대한민국 공개특허 제10-2012-0042083호는 홍마늘 추출물을 포함하는 호흡기 세포 사멸에 의해 유도되는 질환의 예방 및 치료용 조성물에 대한 것으로서, 홍마늘 추출물이 기관지 평활근 세포 내의 글루타티온의 농도 감소를 억제하여 그 사멸을 억제하는 효과가 있음을 개시하고 있다. Republic of Korea Patent Publication No. 10-2012-0042083 relates to a composition for the prevention and treatment of diseases induced by respiratory apoptosis, including red garlic extract, the red garlic extract inhibits the decrease in the concentration of glutathione in bronchial smooth muscle cells It is disclosed that there is an effect of suppressing the death.
하지만, 기관지 평활근 세포의 사멸 이외에 다양한 원인으로 발생하는 호흡기 질환에도 안정적으로 사용할 수 있는 천연추출물에 대한 연구가 요구되는 실정이며, 분꽃나무 추출물의 호흡기 질환의 예방, 개선 내지 치료효과에 대하여는 보고된 바가 없다. However, there is a need for research on natural extracts that can be used stably for respiratory diseases caused by various causes in addition to the death of bronchial smooth muscle cells. none.
이에, 본 발명자들은 분꽃나무의 추출물이 기관지 평활근 세포의 증식을 억제하여 천식 등 호흡기 질환의 예방, 개선 내지 치료에 효과적임을 확인하고, 본 발명을 완성하였다. Accordingly, the present inventors have confirmed that the extract of the branched tree is effective in the prevention, improvement or treatment of respiratory diseases such as asthma by inhibiting the proliferation of bronchial smooth muscle cells, and completed the present invention.
이에, 본 발명자들은 분꽃나무(Viburnum carlesii) 추출물을 포함하는 호흡기 질환 예방, 개선 내지 치료용 조성물을 개발하여 본 발명을 완성하였다.Thus, the present inventors have completed the present invention by developing a composition for the prevention, improvement or treatment of respiratory diseases, including the extract of Viburnum carlesii.
따라서, 본 발명의 목적은 분꽃나무(Viburnum carlesii) 추출물을 포함하는 호흡기 질환 예방 또는 치료용 약학적 조성물을 제공하는 것이다. Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating respiratory diseases, including the extract of Viburnum carlesii.
본 발명의 또 다른 목적은, 분꽃나무(Viburnum carlesii) 추출물을 포함하는 호흡기 질환 예방 또는 개선용 건강기능식품 조성물을 제공하는 것이다. Still another object of the present invention is to provide a dietary supplement for preventing or improving respiratory diseases, including the extract of Viburnum carlesii.
본 발명의 또 다른 목적은, 분꽃나무(Viburnum carlesii) 추출물을 포함하는 호흡기능개선용 건강기능식품 조성물을 제공하는 것이다.Still another object of the present invention is to provide a health functional food composition for respiratory function improvement comprising a extract of Viburnum carlesii.
상기 목적을 달성하기 위해, 본 발명은 분꽃나무(Viburnum carlesii) 추출물을 포함하는 호흡기질환 예방 또는 치료용 약학적 조성물을 제공할 수 있다. In order to achieve the above object, the present invention can provide a pharmaceutical composition for preventing or treating respiratory disease, including the extract of Viburnum carlesii.
본 발명의 바람직한 일실시예에 따르면, 상기 추출물은 분꽃나무의 줄기로부터 수득한 것일 수 있다. According to a preferred embodiment of the present invention, the extract may be obtained from the stem of the branch.
본 발명의 바람직한 일실시예에 따르면, 상기 추출물은 물, 유기용매 또는 이들의 혼합물을 용매로 하여 추출되는 것일 수 있다. According to a preferred embodiment of the present invention, the extract may be extracted by using water, an organic solvent or a mixture thereof as a solvent.
본 발명의 바람직한 일실시예에 따르면, 상기 추출물은 0.3 내지 1000 ㎍/㎖ 농도로 포함되는 것일 수 있다. According to a preferred embodiment of the present invention, the extract is 0.3 to 1000 ㎍ / ㎖ It may be included in the concentration.
본 발명의 바람직한 일실시예에 따르면, 상기 호흡기 질환은 감기, 만성기관지염, 폐기종, 낭포성 섬유증, 염증성 기도질환, 기관지 확장증, 기관지 협착증, 천식, 폐렴 및 폐쇄성 폐질환으로 이루어진 군에서 선택되는 어느 하나 이상인 것일 수 있다. According to a preferred embodiment of the present invention, the respiratory disease is any one selected from the group consisting of cold, chronic bronchitis, emphysema, cystic fibrosis, inflammatory airway disease, bronchiectasis, bronchial stenosis, asthma, pneumonia and obstructive pulmonary disease It may be abnormal.
본 발명의 바람직한 일실시예에 따르면, 상기 조성물은 기관지 평활근세포의 증식을 억제하는 것일 수 있다. According to a preferred embodiment of the present invention, the composition may be to inhibit the proliferation of bronchial smooth muscle cells.
본 발명은 또한, 분꽃나무(Viburnum carlesii) 추출물을 포함하는 호흡기질환 예방 또는 개선용 건강기능식품 조성물을 제공할 수 있다. The present invention may also provide a health functional food composition for preventing or improving respiratory diseases, including an extract of Viburnum carlesii.
본 발명의 바람직한 일실시예에 따르면, 상기 호흡기 질환은 감기, 만성기관지염, 폐기종, 낭포성 섬유증, 염증성 기도질환, 기관지 확장증, 기관지 협착증, 천식, 폐렴 및 폐쇄성 폐질환으로 이루어진 군에서 선택되는 어느 하나 이상인 것일 수 있다. According to a preferred embodiment of the present invention, the respiratory disease is any one selected from the group consisting of cold, chronic bronchitis, emphysema, cystic fibrosis, inflammatory airway disease, bronchiectasis, bronchial stenosis, asthma, pneumonia and obstructive pulmonary disease It may be abnormal.
본 발명은 또한, 분꽃나무(Viburnum carlesii) 추출물을 포함하는 호흡기능개선용 건강기능식품 조성물을 제공할 수 있다. The present invention may also provide a health functional food composition for respiratory function improvement, including an extract of Viburnum carlesii.
따라서, 본 발명의 분꽃나무(Viburnum carlesii) 추출물을 포함하는 조성물은 천식 등 호흡기 질환 환자의 기관지 평활근 세포의 증식을 유의적으로 억제할 수 있으므로 호흡기 질환의 예방, 개선 또는 치료용 조성물로서 효과적이다. Therefore, the composition comprising the extract of Viburnum carlesii of the present invention can significantly inhibit the proliferation of bronchial smooth muscle cells in patients with respiratory diseases such as asthma, and thus is effective as a composition for preventing, improving or treating respiratory diseases.
도 1은 분꽃나무 줄기 추출물이 천식환자의 기관지 평활근 세포에 대하여 세포독성을 나타내지 않음을 나타낸다. 대조군은 DMSO를 처리하였다.
도 2는 천식환자의 기관지 평활근 세포에 분꽃나무 줄기 추출물을 처리하는 경우 기관지 평활근 세포의 증식이 유의적으로 감소하는 것을 나타낸다. 대조군은 DMSO를 처리하였다.Figure 1 shows that the extract of the stem of the flower of the asthma does not show cytotoxicity against bronchial smooth muscle cells of asthma patients. The control group was treated with DMSO.
Figure 2 shows that the treatment of bronchial smooth muscle cells of bronchial smooth muscle cells of asthma patients significantly reduced proliferation of bronchial smooth muscle cells. The control group was treated with DMSO.
이하, 본 발명을 보다 상세히 설명한다. Hereinafter, the present invention will be described in more detail.
상술한 바와 같이, 종래 호흡기 질환의 치료 등에 사용되는 약물은 대부분 면역 내지 염증반응을 조절하는데에 중점이 맞춰져 있어, 염증 이외의 원인으로 발생하는 호흡기 질환에 사용하는 경우 한계가 존재하였다. 이를 극복하기 위하여, 염증을 포함한 다양한 원인에 의해 발생하는 호흡기 질환의 치료 등에 사용할 수 있는 천연추출물 유래의 조성물에 대한 개발이 필요했다. As described above, most of the drugs used in the conventional treatment of respiratory diseases are focused on regulating immune to inflammatory responses, and therefore, there are limitations when used in respiratory diseases caused by causes other than inflammation. In order to overcome this, it was necessary to develop a composition derived from a natural extract that can be used for the treatment of respiratory diseases caused by various causes including inflammation.
본 발명에 따른 분꽃나무(Viburnum carlesii) 추출물을 포함하는 조성물은 기관지 평활근 세포의 증식을 유의적으로 억제하므로 기관지 평활근의 부피증가로 인해 발생하는 호흡기 질환 예방, 개선 또는 치료용 조성물로서 효과적이다. Since the composition comprising the extract of Viburnum carlesii according to the present invention significantly inhibits the proliferation of bronchial smooth muscle cells, it is effective as a composition for preventing, improving or treating respiratory diseases caused by an increase in the volume of bronchial smooth muscle.
따라서, 본 발명은 분꽃나무(Viburnum carlesii) 추출물을 포함하는 호흡기 질환 예방 또는 치료용 약학적 조성물을 제공한다. Accordingly, the present invention provides a pharmaceutical composition for preventing or treating respiratory diseases, including the extract of Viburnum carlesii.
본 발명의 상기 분꽃나무 추출물은 분꽃나무의 꽃, 줄기 또는 잎 등의 지상부에서 추출될 수 있으나, 바람직하게는 줄기에서 수득하는 것이 바람직하다.The branch flower extract of the present invention may be extracted from the ground portion of the flower, stem or leaves of the branch flower, but preferably obtained from the stem.
본 발명의 상기 추출물은 물, 유기용매 또는 이들의 혼합물을 용매로 하여 추출되는 것이 바람직하며, 더욱 바람직하게는 물, C1 내지 C4의 저급 알코올 또는 이들의 혼합물을 용매로 하여 추출되는 것이 바람직하고, 가장 바람직하게는 메탄올을 용매로 하여 추출되는 것이 가장 바람직하나 이에 한정되지 않는다. The extract of the present invention is preferably extracted with water, an organic solvent or a mixture thereof as a solvent, more preferably water, a lower alcohol of C 1 to C 4 or a mixture thereof as a solvent. Most preferably, the solvent is extracted using methanol as a solvent, but is not limited thereto.
본 발명의 상기 추출물은 0.3 내지 1000 ㎍/㎖ 농도로 포함되는 것이 바람직하며, 더욱 바람직하게는 1 내지 300 ㎍/㎖ 농도로 포함되는 것이 바람직하고, 가장 바람직하게는 3 내지 30 ㎍/㎖ 농도로 포함되는 것이 가장 바람직하다. 상기 농도 범위는 분꽃나무 추출물이 기관지 평활근 세포에 독성을 나타내지 않으면서(도 1) 그 증식을 유의적으로 억제할 수 있는 농도 범위에 해당한다. The extract of the present invention is preferably contained in a concentration of 0.3 to 1000 ㎍ / ㎖, more preferably contained in a concentration of 1 to 300 ㎍ / ㎖, most preferably in a concentration of 3 to 30 ㎍ / ㎖ Most preferably included. The concentration range corresponds to a concentration range in which the Asteraceae extract can significantly inhibit its proliferation without showing toxicity to bronchial smooth muscle cells (FIG. 1).
상기 호흡기 질환은 기관지 평활근과 관련된 질환이라면 제한없이 적용 가능하나, 바람직하게는 감기, 만성기관지염, 폐기종, 낭포성 섬유증, 염증성 기도질환, 기관지 확장증, 기관지 협착증, 천식, 폐렴 및 폐쇄성 폐질환으로 이루어진 군에서 선택되는 어느 하나 이상인 것이 바람직하다.The respiratory disease can be applied without limitation as long as it is a disease associated with bronchial smooth muscle, preferably, cold, chronic bronchitis, emphysema, cystic fibrosis, inflammatory airway disease, bronchiectasis, bronchial stenosis, asthma, pneumonia and obstructive pulmonary disease It is preferably at least one selected from the group.
본 발명의 천식은 아토피성 천식, 비-아토피성 천식, 알레르기성 천식, 아토피성 기관지 IgE-매개된 천식, 기관지 천식, 본태성 천식, 진성 천식, 병태생리학적 교란에 의해 유발되는 내인성 천식, 환경적 인자에 의해 유발되는 외인성 천식, 원인이 밝혀지지 않거나 불분명한 본태성 천식, 비-아토피성 천식, 기관지염성 천식, 폐기종성 천식, 운동에 의해 유발되는 천식, 알레르기원에 의해 유발되는 천식, 찬 공기에 의해 유발되는 천식, 직업성 천식, 세균, 진균, 원충 또는 바이러스 감염에 의해 유발되는 감염성 천식, 비-알레르기성 천식, 초기 천식, 천명음을 내는 유아(wheezy infant) 증후군 및 세기관지염으로 이루어진 군에서 선택된 어느 하나 이상의 천식을 포함하나, 이에 한정되는 것은 아니다. Asthma of the present invention is atopic asthma, non-atopic asthma, allergic asthma, atopic bronchial IgE-mediated asthma, bronchial asthma, essential asthma, intrinsic asthma, endogenous asthma caused by pathophysiological disturbance, environment Exogenous asthma caused by enemy factors, essential asthma with unknown or unclear causes, non-atopic asthma, bronchitis asthma, emphysema asthma, asthma caused by exercise, asthma caused by allergens, cold In the group consisting of air-induced asthma, occupational asthma, infectious asthma, non-allergic asthma, early asthma, whistle infant syndrome and bronchiolitis caused by bacterial, fungal, protozoa or viral infections At least one selected asthma, but is not limited thereto.
상기 호흡기 질환 환자의 기관지 평활근세포는 정상인의 기관지 평활근세포에 비하여 상대적으로 비후하다. 이는 세포수의 증가 또는 세포사멸(apoptosis)의 감소 등을 원인으로 하는데, 그 중 세포수의 증가는 기관지 평활근 세포의 증식 내지 이주가 활발히 일어나기 때문이다. 본 발명의 분꽃나무 추출물을 포함하는 조성물은 기관지 평활근 세포의 증식을 억제함으로써 호흡기 질환 환자의 기도개형 증상을 완화할 수 있다. 특히, 분꽃나무 추출물의 농도가 30 ㎍/㎖ 내지 그 이상 처리되는 경우 기관지 평활근 세포의 증식 억제 효과가 더욱 유의적으로 나타난다(도 2). The bronchial smooth muscle cells of the respiratory disease patients are thicker than those of normal bronchial smooth muscle cells. This is caused by an increase in cell number or a decrease in apoptosis, and the increase in cell number is caused by the proliferation or migration of bronchial smooth muscle cells. Compositions comprising the extract of the branch of the present invention can alleviate airway remodeling symptoms of patients with respiratory diseases by inhibiting the proliferation of bronchial smooth muscle cells. In particular, the effect of inhibiting the proliferation of bronchial smooth muscle cells is more significant when the concentration of the extract of
본 발명의 조성물은 경구 또는 비경구의 여러 가지 제형일 수 있다. 상기 조성물을 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다.The compositions of the present invention may be in various oral or parenteral formulations. In formulating the composition, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants are usually used.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 하나 이상의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한, 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제들도 사용된다. 경구투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 또는 시럽제 등이 해당되는데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제 또는 보존제 등이 포함될 수 있다.Solid form preparations for oral administration include tablets, pills, powders, granules, capsules and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin. In addition to simple excipients, lubricants such as magnesium stearate, talc and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions or syrups, and include various excipients such as wetting agents, sweeteners, fragrances, or preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Can be.
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁용제, 유제, 동결건조제제 또는 좌제 등이 포함된다. 비수성용제 및 현탁용제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세롤, 젤라틴 등이 사용될 수 있다.Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations or suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol, gelatin and the like can be used.
본 발명의 조성물은 경구 또는 비경구로 투여될 수 있으며, 비경구 투여시 피부외용 또는 복강내, 직장, 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 주사 방식을 선택하는 것이 바람직하다.The composition of the present invention may be administered orally or parenterally, and when parenteral administration, it is preferable to select an external skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injection mode.
본 발명의 조성물은 약제학적으로 유효한 양으로 투여한다. 약제학적으로 유효한 양이란 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 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 부작용없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The composition of the present invention is administered in a pharmaceutically effective amount. A pharmaceutically effective amount means an amount sufficient to treat the disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type, severity, activity of the drug, sensitivity to the drug, and administration of the patient. Time, route of administration and rate of release, duration of treatment, factors including concurrent use of drugs, and other factors well known in the medical arts. The compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can achieve the maximum effect with a minimum amount without side effects, which can be readily determined by one skilled in the art.
본 발명의 조성물의 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도에 따라 그 범위가 다양하며, 일일 투여량은 분꽃나무 추출물의 양을 기준으로 0.01 내지 1000 ㎎/㎏이고, 바람직하게는 30 내지 500 ㎎/㎏이고, 더욱 바람직하게는 50 내지 300 ㎎/㎏이며, 하루 1 ~ 6 회 투여될 수있다. 그러나 투여 경로, 비만의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.The dosage of the composition of the present invention varies depending on the weight, age, sex, health condition, diet, time of administration, method of administration, excretion rate and severity of the disease of the patient, the daily dosage is the amount of the extract 0.01 to 1000 mg / kg, preferably 30 to 500 mg / kg, more preferably 50 to 300 mg / kg, and may be administered 1 to 6 times per day. However, the dosage may be increased or decreased depending on the route of administration, the severity of obesity, sex, weight, age, etc., and the above dosage does not limit the scope of the present invention in any way.
본 발명의 조성물은 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The compositions of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers.
따라서, 분꽃나무(Viburnum carlesii) 추출물은 기관지 평활근 세포의 증식을 유의적으로 억제하므로 호흡기 질환 예방 또는 치료용 약학적 조성물로서 효과적이다. Therefore, the extract of Viburnum carlesii significantly inhibits the proliferation of bronchial smooth muscle cells and thus is effective as a pharmaceutical composition for preventing or treating respiratory diseases.
본 발명은 또한, 분꽃나무(Viburnum carlesii) 추출물을 포함하는 호흡기 질환 예방 또는 개선용 건강기능식품 조성물을 제공한다. 상기 분꽃나무 추출물은 상기 약학적 조성물에 포함된 분꽃나무 추출물과 동일하므로, 이에 대한 기재로 대신한다. The present invention also provides a dietary supplement for preventing or improving respiratory diseases, including the extract of Viburnum carlesii. Since the branch flower extract is the same as the branch flower extract contained in the pharmaceutical composition, it is replaced by the description thereof.
본 발명의 상기 호흡기 질환은 감기, 만성기관지염, 폐기종, 낭포성 섬유증, 염증성 기도질환, 기관지 확장증, 기관지 협착증, 천식, 폐렴 및 폐쇄성 폐질환으로 이루어진 군에서 선택되는 어느 하나 이상인 것이 바람직하나, 기관지 평활근 세포의 증식으로 인해 발생하는 질환이라면 제한없이 적용 가능하다. The respiratory disease of the present invention is preferably at least one selected from the group consisting of cold, chronic bronchitis, emphysema, cystic fibrosis, inflammatory airway disease, bronchiectasis, bronchial stenosis, asthma, pneumonia and obstructive pulmonary disease, bronchial smooth muscle Any disease caused by the proliferation of cells can be applied without limitation.
본 발명은 또한, 분꽃나무(Viburnum carlesii) 추출물을 포함하는 호흡기능개선용 건강기능식품 조성물을 제공한다. 상기 분꽃나무 추출물은 상기 약학적 조성물에 포함된 분꽃나무 추출물과 동일하므로, 이에 대한 기재로 대신한다. The present invention also provides a health functional food composition for respiratory function improvement comprising the extract of Viburnum carlesii. Since the branch flower extract is the same as the branch flower extract contained in the pharmaceutical composition, it is replaced by the description thereof.
상기 “호흡기능개선”은 호흡기능이 질적 또는 양적으로 향상되는 모든 효과를 의미한다. The "improved breathing function" means any effect that the respiratory function is improved qualitatively or quantitatively.
본 발명의 분꽃나무 추출물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 본 발명의 건강식품은 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소 및 조미제를 포함한다.The flowering branch of the present invention can be added as it is or used with other foods or food ingredients, and can be suitably used according to conventional methods. The health food of the present invention includes ingredients that are commonly added in food production, and include, for example, proteins, carbohydrates, fats, nutrients and seasonings.
상기 식품의 종류에는 특별한 제한은 없다. 상기 분꽃나무 추출물을 첨가할 수 있는 식품의 예로는 드링크제, 육류, 소시지, 빵, 비스킷, 떡, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 알코올 음료 및 비타민 복합제, 유제품 및 유가공 제품 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of foods to which the branch extract may be added include drinks, meat, sausages, breads, biscuits, rice cakes, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum products, dairy products including ice cream, various Soups, beverages, alcoholic beverages and vitamin complexes, dairy products and dairy products, and the like, and include all dietary supplements in the conventional sense.
본 발명의 분꽃나무 추출물은 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합량은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강식품 중의 상기 추출물의 양은 전체 식품 중량의 0.1 내지 90 중량부로 가할 수 있다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.The branch flower extract of the present invention may be added to the food as it is or used with other food or food ingredients, and may be appropriately used according to conventional methods. The mixing amount of the active ingredient can be suitably determined according to the purpose of use (prevention or improvement). In general, the amount of the extract in the health food can be added to 0.1 to 90 parts by weight of the total food weight. However, in the case of long-term intake for health and hygiene or health control purposes, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.
본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 본 발명의 추출물을 함유하는 것 외에는 다른 성분에 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health functional beverage composition of the present invention is not particularly limited to other ingredients except for containing the extract of the present invention as an essential ingredient in the indicated proportions, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Can be. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tautin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 compositions of the present invention.
상기 외에 본 발명의 분꽃나무 추출물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 분꽃나무 추출물은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 분꽃나무 추출물 100 중량부당 0.1 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the branch flower extract of the present invention may be used in various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavoring agents, colorants and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid And salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. In addition, the branch flower extract may contain pulp for the production of natural fruit juice and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical, but is generally selected from the range of 0.1 to about 20 parts by weight per 100 parts by weight of the branch flower extract of the present invention.
따라서, 분꽃나무(Viburnum carlesii) 추출물은 기관지 평활근 세포의 증식을 유의적으로 억제하므로 호흡기 질환 예방 또는 개선용 내지 호흡기능개선용 건강기능식품 조성물로서 효과적이다.Therefore, the extract of Viburnum carlesii significantly inhibits the proliferation of bronchial smooth muscle cells and thus is effective as a health functional food composition for preventing or improving respiratory diseases or improving respiratory function.
이하, 실시예 및 제조예를 통하여 본 발명을 보다 상세히 설명하고자 한다. 이들 실시예 및 제조예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예 및 제조예에 의해 제한되는 것으로 해석되지 않는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다. Hereinafter, the present invention will be described in more detail with reference to Examples and Preparation Examples. These examples and preparations are only for illustrating the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not interpreted to be limited by these examples and preparations. .
분꽃나무 추출물의 제조 Preparation of the branch flower extract
분꽃나무의 추출물에 호흡기능개선 효과가 있는지 여부를 확인하기 위하여 분꽃나무 줄기의 추출물을 제조하고자 하였다. The purpose of this study was to prepare the extracts of the stems of the flowering branches in order to check whether the extracts of the flowering trees have a respiratory function.
구체적으로, 분꽃나무 줄기의 추출물을 제조하기 위하여 분꽃나무 줄기 원시료를 메탄올(Methanol, Methyl alcohol) 99.9%에 넣어 45℃에서 3일(15분 sonication 후 2시간 정치, 10회/1일)동안 추출을 실시하였고, Filter로 무형광 솜을 사용하여 여과하였으며 45℃에서 농축하여 제조하였다.Specifically, in order to prepare the extracts of the stems of the flowering trunks, the raw materials of the flowering trunks of methanol were added to 99.9% of methanol (Methanol, Methyl alcohol) for 3 days at 45 ° C. (2 hours after 15 minutes sonication, 10 times / 1 day). The extraction was carried out, filtered using a non-fluorescent cotton as a filter and concentrated at 45 ℃ prepared.
기관지 평활근 세포(DBSMC-AS)의 배양 Culture of Bronchial Smooth Muscle Cells (DBSMC-AS)
분꽃나무의 추출물을 처리하는 경우 천식환자의 기관지 평활근세포의 증식이 효과적으로 억제되는지 여부를 확인하기 위하여 천식환자의 기관지 평활근세포를 배양하고자 하였다. In order to determine whether bronchial smooth muscle cell proliferation of asthma patients is effectively inhibited when the extracts of the cherry blossoms are treated, we tried to culture bronchial smooth muscle cells of asthma patients.
천식환자의 기관지 평활근세포(DBSMC-AS(Diseased Bronchial Smooth Muscle cell-Asthma); Lonza, 194850)를 5% 소태아혈청(FBS; fetal bovine serum), 0.1% rhEGF, 0.1% 인슐린(Insulin), 0.1% GA-1000, 0.2% rhFGF-B를 함유하는 SMBM 배지를 이용하여 5% CO2가 존재하는 37℃ 배양기에서 배양하였다. 3 내지 20 세대(passage)사이의 세포를 실험에 이용하였다. Bronchial smooth muscle cells of asthma patients (DBSMC-AS (Diseased Bronchial Smooth Muscle cell-Asthma); Lonza, 194850) were treated with 5% fetal bovine serum (FBS), 0.1% rhEGF, 0.1% insulin SMBM medium containing% GA-1000, 0.2% rhFGF-B was incubated in a 37 ° C. incubator with 5% CO 2 . Cells between 3 and 20 generations were used for the experiment.
분꽃나무 추출물의 세포독성 확인 Confirmation of Cytotoxicity of the Branches
분꽃나무 줄기 추출물이 천식환자의 기관지 평활근 세포에 독성을 나타내는지 여부를 확인하기 위하여 MTT 세포독성 실험을 수행하였다. MTT cytotoxicity experiments were performed to determine whether the extracts from the stems of the Aspen are toxic to bronchial smooth muscle cells of asthma patients.
구체적으로, 분꽃나무 줄기 추출물에 대한 천식환자의 기관지 평활근 세포의 생존율을 조사하기 위하여 24 웰(well)에 5×105 cells/well 씩 세포를 도말하고 24시간 후에 분꽃나무 줄기 추출물(3, 10 또는 30㎍/㎖)을 처리하였고, 대조군(CTL)으로 DMSO 0.1%를 처리하여 24시간동안 배양하였다. 그 후 배양액을 제거하고 MTT(3-(4,5-Dimethylthiazol-2-yl)-2)를 1XPBS에 녹여 0.005 g/㎖로 만든 후 well 당 500 ㎕씩 첨가하여 37℃, 5% CO2 배양기에서 1시간 반응시켰다. 그 후 상층액을 제거하고 DMSO를 첨가하여 녹인 후 96 웰에 100 ㎕씩 분주한 후 Microplate Autoreader ELISA(Bio-Tek Instruments Inc., Winooski, VT)를 사용하여 570 ㎚에서 흡광도를 측정하여 세포 생존율을 확인하였다.Specifically, in order to investigate the survival rate of bronchial smooth muscle cells of asthma patients against the stem extract of the aspen, 5 × 10 5 cells / well in 24 wells, and after 24 hours, the stem extract (3, 10 Or 30 μg / ml) and treated with 0.1% DMSO as a control (CTL) and incubated for 24 hours. After that, remove the culture medium, dissolve MTT (3- (4,5-Dimethylthiazol-2-yl) -2) in 1XPBS to make 0.005 g / mL, and add 500 μl of each well at 37 ° C for 5% CO 2 incubator. Reaction was carried out for 1 hour. Subsequently, the supernatant was removed, dissolved by adding DMSO, and then, 100 µl was dispensed into 96 wells, followed by measurement of absorbance at 570 nm using a Microplate Autoreader ELISA (Bio-Tek Instruments Inc., Winooski, VT). Confirmed.
그 결과, [도 1]에서 나타나는 바와 같이 분꽃나무 줄기 추출물은 천식환자의 기관지 평활근 세포에 대하여 독성을 나타내지 않는 것을 확인할 수 있었다. As a result, as shown in [Fig. 1] it was confirmed that the branch stem extract does not show toxicity to bronchial smooth muscle cells of asthma patients.
천식환자의 기관지 평활근 세포의 증식 여부 측정Measurement of Bronchial Smooth Muscle Cell Proliferation in Asthmatic Patients
분꽃나무의 줄기 추출물을 처리하는 경우 천식환자의 기관지 평활근세포의 증식이 효과적으로 억제되는지 여부를 확인하기 위하여 천식환자의 기관지 평활근세포에 분꽃나무의 줄기 추출물을 처리하여 상기 세포의 증식 여부를 측정하고자 하였다. In order to determine whether the proliferation of bronchial smooth muscle cells of asthma patients was effectively inhibited when the stem extracts of the flowering trees were treated, the stem extracts of the broccoli smooth stem cells of asthma patients were treated to determine the proliferation of the cells. .
구체적으로, 96 웰(well) 에서 배양된 천식환자의 기관지 평활근세포를 12시간 0.1% FBS가 첨가된 배지에 가사상태로 배양(starvation) 후 [실시예 1]에서 제조한 분꽃나무 줄기 추출물 10㎍/㎖을 처리하여 배양하였다. 24시간 뒤 각 그룹별 세포를 BrdU kit를 이용한 ELISA 측정을 통하여 증식된 세포수를 측정하였다. 대조군(CTL)은 DMSO 0.1%를 처리하였다. Specifically, bronchial smooth muscle cells of asthma patients cultured in 96 wells (starvation) in a medium containing 12% 0.1% FBS for 12 hours after starvation (10 minutes) Incubated with / ml treatment. After 24 hours, the cell number of each group was measured by measuring ELISA using BrdU kit. The control group (CTL) was treated with 0.1% DMSO.
그 결과, [도 2]과 같이 천식환자의 기관지 평활근 세포의 증식이 대조군에 비하여 유의적으로 감소하였다.As a result, the proliferation of bronchial smooth muscle cells of asthma patients as shown in FIG. 2 was significantly reduced compared to the control group.
<제조예 1-1> 분꽃나무 추출물을 포함하는 정제 Preparation Example 1-1 A Tablet Comprising a Branch Flower Extract
전분 - - - - - - - - - - 50 mgStarch----------50 mg
유당 - - - - - - - - - - 50 mgLactose----------50 mg
스테아린산 마그네슘 - - - 5 mgMagnesium Stearate---5 mg
분꽃나무 추출물 - - - - 100 mgBirch Extract----100 mg
상기 성분들을 혼합하고 통상적인 정제의 제조방법에 따라 습식과립법 또는 건식과립법을 이용하여 정제를 제조하였다. The tablets were prepared by mixing the components and using a wet granulation method or a dry granulation method according to a conventional method for preparing a tablet.
<제조예 1-2> 분꽃나무 추출물을 포함하는 건강음료 Preparation Example 1-2 Health Beverage Containing Branches Extract
액상과당 - - - - - - - - - - - - - - - 0.5%Liquid fructose---------------0.5%
올리고당 - - - - - - - - - - - - - - - 2%Oligosaccharide----------------2%
설탕 - - - - - - - - - - - - - - - - - 2%Sugar------------------2%
식염 - - - - - - - - - - - - - - - - - 0.5%Salt------------------0.5%
물 - - - - - - - - - - - - - - - - - - 75%Water-------------------75%
분꽃나무 추출물 - - - - - - - - - - - 20%Birch Extract------------20%
상기 성분들을 혼합하여 총 용량이 50 ㎖가 되도록 하고, 혼합액을 3 ㎛ 필터로 여과시킨 최종 혼합액을 90 내지 93 ℃에서 20초간 1차 살균하여 50 ㎖ 병에 충진한 후 80 내지 85 ℃에서 20분간 2차 살균하여 건강음료제품을 제조하였다. The ingredients were mixed to a total volume of 50 ml, and the final mixture was filtered through a 3 μm filter and sterilized for 20 seconds at 90-93 ° C. for 20 seconds, and then filled into a 50 ml bottle for 20 minutes at 80-85 ° C. Secondary sterilization produced a health beverage product.
Claims (9)
Pharmaceutical composition for preventing or treating respiratory diseases, including the extract of Viburnum carlesii.
According to claim 1, wherein the extract is a pharmaceutical composition for preventing or treating respiratory diseases, characterized in that obtained from the stem of the flowering tree.
The pharmaceutical composition for preventing or treating respiratory diseases according to claim 1, wherein the extract is extracted using water, an organic solvent or a mixture thereof as a solvent.
According to claim 1, wherein the extract is a pharmaceutical composition for preventing or treating respiratory diseases, characterized in that it comprises a concentration of 0.3 to 1000 ㎍ / ㎖.
The method of claim 1, wherein the respiratory disease is any one or more selected from the group consisting of cold, inflammatory airway disease, bronchiectasis, bronchial stenosis, asthma, pneumonia and obstructive pulmonary disease Composition.
According to claim 1, wherein the composition is a pharmaceutical composition for preventing or treating respiratory diseases, characterized in that to inhibit the proliferation of bronchial smooth muscle cells.
Health functional food composition for preventing or improving respiratory diseases, including the extract of Viburnum carlesii.
The method of claim 7, wherein the respiratory disease is any one or more selected from the group consisting of cold, inflammatory airway disease, bronchiectasis, bronchial stenosis, asthma, pneumonia and obstructive pulmonary disease Food composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020180097476A KR20200021739A (en) | 2018-08-21 | 2018-08-21 | Composition comprising Viburnum carlesii extract for preventing, improving or treating respiratory disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020180097476A KR20200021739A (en) | 2018-08-21 | 2018-08-21 | Composition comprising Viburnum carlesii extract for preventing, improving or treating respiratory disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20200021739A true KR20200021739A (en) | 2020-03-02 |
Family
ID=69805335
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020180097476A KR20200021739A (en) | 2018-08-21 | 2018-08-21 | Composition comprising Viburnum carlesii extract for preventing, improving or treating respiratory disease |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR20200021739A (en) |
-
2018
- 2018-08-21 KR KR1020180097476A patent/KR20200021739A/en not_active Application Discontinuation
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