KR20190109926A - Composition for Anti-Arthritis Using a Leaf Extract of Ficus erecta Thunb. var. sieboldii(Miq.)King - Google Patents
Composition for Anti-Arthritis Using a Leaf Extract of Ficus erecta Thunb. var. sieboldii(Miq.)King Download PDFInfo
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- KR20190109926A KR20190109926A KR1020180031634A KR20180031634A KR20190109926A KR 20190109926 A KR20190109926 A KR 20190109926A KR 1020180031634 A KR1020180031634 A KR 1020180031634A KR 20180031634 A KR20180031634 A KR 20180031634A KR 20190109926 A KR20190109926 A KR 20190109926A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
Abstract
Description
본 발명은 좁은잎천선과(Ficus erecta Thunb. var. sieboldii(Miq.)King) 잎 추출물을 이용한 관절염 개선용 조성물에 관한 것이다.The present invention relates to a composition for improving arthritis using a ficus erecta Thunb.var.sieboldii (Miq.) King leaf extract.
1998년과 2001년도 국민건강영양조사에 의하면 관절염은 45세 이상에서 흔한 만성질환이었으며 관절염의 유병률은 연령에 따라 증가하여 65세 이상 인구에서는 1998년 천명 당 356.7명, 2001년 364.2명을 차지하였다(Korea National Health and Nutrition Examination Survey. 2001. Ministry of Health and Welfare. Seoul, Korea. p 51). 최근 '2010년 고령자 통계'에 따르면 우리나라 65세 이상 노인인구 비율은 11%로서 인구 구조의 고령화에 따라 만성퇴행성 질환 유병률 또한 증가하고 있고, 연간 유병률이 높은 만성질환으로서 관절염이 43.1% 이상 차지하고 있다(Senior Statistical Reports. 2010. The Statistics Korea. Daejeon, Korea. p 5).According to the 1998 and 2001 National Health and Nutrition Examination, arthritis was a common chronic disease in over 45 years of age, and the prevalence of arthritis increased with age, accounting for 356.7 per thousand people in 1998 and 364.2 in 2001 for people over 65 years old. Korea National Health and Nutrition Examination Survey.2001.Ministry of Health and Welfare.Seoul, Korea.p 51). According to the recent statistics on elderly people in 2010, the proportion of elderly people aged 65 or older in Korea is 11%, and the prevalence of chronic degenerative diseases is increasing with the aging of the population, and the chronic disease with a high annual prevalence accounts for 43.1% or more. Senior Statistical Reports.2010.The Statistics Korea.Daejeon, Korea.p 5).
관절염은 통증, 강직, 부종 등이 동반되는 질환으로 그 원인은 퇴행성 변화, 면역계 이상, 감염, 외상, 대사 장애 등이며 그 종류는 100여 가지가 넘는다(J Knee Surg 24: 251-264, 2011). 그 중 골관절염(osteoarthritis)과 류마티스(rheumatoid arthritis, RA) 관절염이 전체 관절염의 80%를 차지하고 있으며 근골격계 질환으로 인한 부담 중 가장 많은 부분을 차지한다.Arthritis is a disease that is accompanied by pain, stiffness, and swelling. The causes are degenerative changes, immune system abnormalities, infections, trauma, and metabolic disorders (J Knee Surg 24: 251-264, 2011). . Of these, osteoarthritis and rheumatoid arthritis (RA) arthritis account for 80% of all arthritis and account for the largest part of the burden of musculoskeletal disorders.
골관절염(osteoarthritis)은 관절 연골이 닳아 없어지면서 비롯되는 퇴행성 질환으로, 관절 통증, 근육 위축 및 근력 약화 등의 증상을 초래하고, 남성들보다는 여성들 환자가 많은 편이고 체중부하를 많이 받는 슬관절 및 고관절 등의 부위에 많이 발생한다(Obes. Rev. 7:239-250, 2006; Arthritis Rheuma. 26:1039-1049, 1986). 골관절염은 관절의 충격, 염증성 인자, 호르몬 분비 이상, 감염, 퇴행성 변화, 유전적 요인 등 다양한 원인에 의해 발생하나 아직까지 정확한 원인은 규명되지는 않았다.Osteoarthritis is a degenerative disease caused by the wear and tear of joint cartilage, which causes symptoms such as joint pain, muscle atrophy and muscle weakness. Many occur in the site (Obes. Rev. 7: 239-250, 2006; Arthritis Rheuma. 26: 1039-1049, 1986). Osteoarthritis is caused by various causes such as joint shock, inflammatory factors, abnormal hormone secretion, infection, degenerative changes, and genetic factors, but the exact cause has not been identified.
골관절염의 발병과 관련된 인자들로는 주로 단백질 가수분해 효소(proteolytic enzymes), 사이토카인 등이 알려져 있다. 연골조직에서의 물질 대사 과정은 연골조직의 퇴화에 중추적인 역할을 하며(Phytochemistry 7: 237-243, 2009), 대표적으로 MMPs(matrix metalloproteinases)는 골 및 연골의 기질 구성요소를 파괴하는 단백 분해효소로서 관절염 등의 병적인 상태에서도 발현되어 병인에 주요한 역할을 하는 것으로 알려져 있다(Osteoarthritis Cartilage 9: 751-760, 2001; Clin Calcium 19: 1593-1601, 2009). 관절염 발병시 발현이 증가하는 MMPs로 MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-7 그리고 MMP-13 등이 있다(Ann Rheum Dis 59: 455-461, 2000).Factors related to the development of osteoarthritis are mainly known proteolytic enzymes, cytokines and the like. Metabolic processes in cartilage tissue play a pivotal role in the degeneration of cartilage tissue (Phytochemistry 7: 237-243, 2009), and typically matrix metalloproteinases (MMPs) are proteinases that destroy the matrix components of bone and cartilage. It is also expressed in pathological conditions such as arthritis and is known to play a major role in pathogenesis (Osteoarthritis Cartilage 9: 751-760, 2001; Clin Calcium 19: 1593-1601, 2009). MMPs with increased expression during arthritis include MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-7 and MMP-13 (Ann Rheum Dis 59: 455-461, 2000). ).
좁은잎 천선과는 무화과과에 속하는 식물로서 가는잎천선과나무라고도 하며 우리나라에서도 제주도와 남해안 지방 특히 제주도에 주로 자라는 나무이다. 바닷가 산기슭에서 자라며 높이 2~4m이고, 나무껍질은 잿빛이 섞인 흰색이며 어두운 갈색 피목이 있고 털이 없다. 잎은 어긋나고 천선과 보다 좁은 바소꼴이며 길이 10~20cm이다. 끝부분이 뾰족하고 가장자리는 밋밋하거나 거친 톱니가 난다. 곁맥은 5~6쌍이고 잎자루는 길이 1~4cm이다(이창복, 1979, 대한식물도감). 좁은잎천선과는 민간에서는 오래전부터 補中(보중), 益氣(익기), 健脾(건비), 化濕(화습), 强筋壯骨(강근장골), 消腫(소종), 活血(활혈), 해독의 효능이 있다. 中氣虛弱(중기허약), 氣血衰微(기혈쇠미), 사디산언(사지에 힘이 없고 나른하다), 筋骨不利(근골불리), 타박상, 經閉(경폐), 産後乳汁缺乏(산후유즙결핍)을 치료 등에 이용되어져 왔다.Narrow-leaved Thymeaceae is a plant belonging to the fig, also called a thin-leafed Thymeaceae, and it is a tree that grows mainly in Jeju Island and the southern coast of Korea, especially Jeju Island. It grows at the foot of the seashore and is 2 ~ 4m high. The bark is white with ash gray, dark brown cork, and hairless. The leaves are alternate, the lanceolate with the narrower bar, and the length is 10-20cm. The tip is pointed and the edge is flat or coarse. Side veins are 5 ~ 6 pairs, petiole is 1 ~ 4cm long (Lee Chang-bok, 1979, Korea Plant Book). In the private sector, the narrow leaf peonies have been used for a long time in 補 中 (보), 益氣 (益氣), 健脾 (脾), 비 (화), 强筋 壯骨 (ganglia), 消腫 (Sojong), 活 ( Live blood), detoxification.中 氣 虛弱 (medium weakness), 氣血 衰微 (blood pressure), Sadisan (less limb and dull limb), 筋骨 不利 (muscle bulge), bruises, 經 閉 (menopause), 産後 乳汁 缺乏 (postpartum milk deficiency) ) Has been used for treatment.
좁은잎천선과에 대해서는 항산화 활성, 항염증 활성, 티로시나아제 억제 활성, 골다공증 개선 활성(윤원종, 제주대학교 석사 학위 논문, 2005; 박성환, 제주대학교 석사 학위 논문, 2011; 한국 공개특허 제2011-0056684호) Antioxidative activity, anti-inflammatory activity, tyrosinase inhibitory activity, osteoporosis improving activity on narrow leaf perennial herb (Yoon Won Jong, Master's Thesis, Cheju National University, 2005; Sung Hwan Park, Master's Thesis, Cheju National University, 2011; Korean Patent Publication No. 2011-0056684 number)
본 발명은 동물실험 등을 통해 확인된 좁은잎천선과 잎 추출물의 관절염 개선 활성을 개시한다.The present invention discloses the arthritis improving activity of the narrow leaf zenith and leaf extract confirmed through animal experiments.
본 발명의 목적은 좁은잎천선과 잎 추출물을 이용한 관절염 개선용 조성물을 제공하는 데 있다.An object of the present invention to provide a composition for improving arthritis using a narrow leaf zenith and leaf extract.
본 발명의 다른 목적이나 구체적인 목적은 이하에서 제시될 것이다.Other and specific objects of the present invention will be presented below.
본 발명자들은 아래의 실시예 및 실험예에서 확인되는 바와 같이, 좁은잎천선과 잎 추출물이 MIA(monosodium iodoacetate)에 의한 골관절염 동물실험에서도 행동 양태(착지, 절뚝거림, 내딛는 양태 등)를 뚜렷하게 개선시키고 사이토카인(IL-1β, TNF-α, IL-6)의 생성을 농도 의존적으로 감소시킬 뿐만 아니라 MMP-2, 3, 7, 9, 13과 TIMP-1, 2의 발현을 현저하게 감소시킴을 확인하였다. 또한 조직손상이 일어나는 지속적인 통증에 대한 효력 시험방법인 Formalin test에서도 뚜렷하게 만성 통증을 억제함을 확인하였다.As confirmed in the following Examples and Experimental Examples, the present inventors have clearly improved the behavioral aspects (landing, limping, stepping, etc.) even in the osteoarthritis animal experiments by MIA (monosodium iodoacetate) Not only does it reduce the production of cytokines (IL-1β, TNF-α, IL-6) in a concentration-dependent manner, but it also significantly reduces the expression of MMP-2, 3, 7, 9, 13 and TIMP-1, 2. Confirmed. In addition, it was confirmed that the Formalin test, which is a test for the effects of continuous pain, in which tissue damage occurs, significantly suppressed chronic pain.
본 발명은 이러한 동물실험을 통하여 확인된 관절염 개선 효과에 기초하여 제공되는 것으로, 본 발명의 관절염 개선용 조성물은 좁은잎천선과 잎 추출물을 그 유효성분으로 포함함을 특징으로 한다. The present invention is provided based on the arthritis improvement effect confirmed through these animal experiments, the composition for arthritis improvement of the present invention is characterized in that it comprises a narrow leaf cheonseon and leaf extract as an active ingredient.
본 명세서에서, "좁은잎천선과 잎 추출물"이란 추출 대상인 좁은잎천선과 잎 을 물, 메탄올, 에탄올, 부탄올 등의 탄소수 1 내지 4의 저급 알콜, 메틸렌클로라이드, 에틸렌, 아세톤, 헥산, 에테르, 클로로포름, 에틸아세테이트, 부틸아세테이트, N,N-디메틸포름아미드(DMF), 디메틸설폭사이드(DMSO), 1,3-부틸렌글리콜, 프로필렌글리콜 또는 이들의 혼합 용매를 사용하여 침출하여 얻어진 추출물, 이산화탄소, 펜탄 등 초임계 추출용매를 사용하여 얻어진 추출물 또는 그 추출물을 분획하여 얻어진 분획물을 의미하며, 추출 방법은 활성물질의 극성, 추출 정도, 보존 정도를 고려하여 냉침, 환류, 가온, 초음파 방사, 초임계 추출 등 임의의 방식이 적용될 수 있다. 분획된 추출물의 경우 상기 추출물을 특정 용매에 현탁시킨 후 극성이 다른 용매와 혼합·정치시켜 얻은 분획물, 상기 추출물을 실리카겔 등이 충진된 칼럼에 흡착시킨 후 소수성 용매, 친수성 용매 또는 이들의 혼합 용매를 이동상으로 하여 얻은 분획물을 포함하는 의미이다. 또한 상기 추출물의 의미에는 동결건조, 진공건조, 열풍건조, 분무건조 등의 방식으로 추출 용매가 제거된 농축된 액상의 추출물 또는 고형상의 추출물이 포함된다. 바람직하게는 추출용매로서 물, 에탄올 또는 이들의 혼합 용매를 사용하여 얻어진 추출물, 더 바람직하게는 추출용매로서 물과 에탄올의 혼합 용매를 사용하여 얻어진 추출물을 의미한다.In the present specification, the "narrow leaf zenith and leaf extract" refers to the narrow leaf zenith and leaves to be extracted, such as water, methanol, ethanol, butanol lower alcohol having 1 to 4 carbon atoms, methylene chloride, ethylene, acetone, hexane, ether, chloroform , Extracts obtained by leaching using ethyl acetate, butyl acetate, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol or a mixed solvent thereof, carbon dioxide, An extract obtained by using a supercritical extracting solvent such as pentane or a fraction obtained by fractionating the extract, and the extraction method is cold, reflux, warm, ultrasonic radiation, supercritical in consideration of the polarity, the degree of extraction, and the degree of preservation of the active substance. Any method such as extraction may be applied. In the case of the fractionated extract, the fraction obtained by suspending the extract in a specific solvent and mixing and standing with a solvent having a different polarity, adsorbing the extract on a column filled with silica gel or the like, and then using a hydrophobic solvent, a hydrophilic solvent, or a mixed solvent thereof It is meant to include fractions obtained by mobile phase. In addition, the meaning of the extract includes a concentrated liquid extract or solid extract in which the extraction solvent is removed in a manner such as freeze drying, vacuum drying, hot air drying, spray drying, and the like. Preferably it refers to an extract obtained by using water, ethanol or a mixed solvent thereof as the extraction solvent, more preferably an extract obtained by using a mixed solvent of water and ethanol as the extraction solvent.
또 본 명세서에서 "유효성분"이란 단독으로 목적하는 활성을 나타내거나 또는 그 자체는 활성이 없는 담체와 함께 활성을 나타낼 수 있는 성분을 의미한다.In addition, the term "active ingredient" as used herein means a component that can exhibit the desired activity alone or in combination with a carrier that is not active itself.
또한 본 명세서에서, 상기 "관절염"이란, 골관절염(퇴행성 관절염), 류마티스 관절염, 화농성 관절염, 강직 척추염(ankylosing spondylitis), 소아 특발성 관절염(juvenile idiopathic arthritis) 또는 스틸병(Still's disease)을 의미한다.In addition, in the present specification, "arthritis" means osteoarthritis (degenerative arthritis), rheumatoid arthritis, purulent arthritis, ankylosing spondylitis, juvenile idiopathic arthritis or Still's disease.
또 본 명세서에서, "관절염 개선"이란 관절염 치료, 예방, 발병 억제, 발병 지연, 증상의 경감을 포함하는 의미이다.In addition, in this specification, "arthritis improvement" is meant to include arthritis treatment, prevention, prevention of onset, delayed onset, alleviation of symptoms.
본 발명의 관절염 개선용 조성물에서 그 유효성분은 그것이 관절염 개선 활성을 나타낼 수 있는 한, 용도, 제형, 배합 목적 등에 따라 임의의 양(유효량)으로 포함될 수 있는데, 통상적인 유효량은 조성물 전체 중량을 기준으로 할 때 0.001 중량 % 내지 20.0 중량 % 범위 내에서 결정될 것이다. 여기서 "유효량"이란 그 적용 대상인 포유동물 바람직하게는 사람에게 의료 전문가 등의 제언에 의한 투여 기간 동안 본 발명의 조성물이 투여될 때, 관절염 개선 효과 등 의도한 의료적·약리학적 효과를 나타낼 수 있는, 본 발명의 조성물에 포함되는 유효성분의 양을 말한다. 이러한 유효량은 당업자의 통상의 능력 범위 내에서 실험적으로 결정될 수 있다. The active ingredient in the composition for improving arthritis of the present invention may be included in any amount (effective amount) depending on the purpose, formulation, formulation purpose, etc., as long as it can exhibit arthritis improving activity, and a typical effective amount is based on the total weight of the composition It will be determined in the range of 0.001% to 20.0% by weight. The term "effective amount" herein refers to a mammal, preferably a human subject, which may exhibit an intended medical and pharmacological effect, such as an arthritis-improving effect, when the composition of the present invention is administered to a mammal according to a recommendation of a medical professional or the like. , Refers to the amount of the active ingredient included in the composition of the present invention. Such effective amounts can be determined experimentally within the range of ordinary skill in the art.
본 발명의 조성물이 적용(처방)될 수 있는 대상은 포유동물 및 사람이며, 특히 사람인 경우가 바람직하다.Subjects to which the compositions of the invention can be applied (prescribed) are mammals and humans, in particular humans.
본 발명의 관절염 개선용 조성물은 유효성분 이외에, 관절염 개선 효과의 상승·보강을 위하여 이미 안전성이 검증되고 관절염 개선 활성을 갖는 것으로 공지된 임의의 화합물이나 천연 추출물을 추가로 포함할 수 있다. 구체적으로 그러한 화합물 또는 추출물로서는 건강기능식품에관한법률에 따른 건강기능식품공전(식약처 고시, 건강기능식품의 기준 및 규격)상의 글루코사민, N-아세틸글루코사민, 뮤코다당·단백, 디메틸설폰(Dimethylsulfonylmethane) 이외에, 건강기능식품에관한법률에 따라 개별인정을 받은 CMO 함유 FAC(Fatty acid Complex), 가시오갈피 등 복합추출물, 강황 추출물, 글루코사민, 닭가슴 연골 분말, 로즈힙 분말, 보스웰리아 추출물, 비즈왁스알코올, 전칠삼 추출물 등 복합물, 지방산 복합물, 차조기 등 복합 추출물, 초록입홍합 추출 오일, 호프 추출물, 황금 추출물 등 복합물 등을 들 수 있다. 이러한 화합물 또는 천연 추출물은 본 발명의 관절염 개선용 조성물에 그 유효성분과 함께 하나 이상 포함될 수 있다.In addition to the active ingredient, the composition for improving arthritis of the present invention may further include any compound or natural extract known to have safety and arthritis improving activity for the enhancement and enhancement of the arthritis improving effect. Specifically, such compounds or extracts include glucosamine, N-acetylglucosamine, mucopolysaccharides, proteins, and dimethylsulfone (Dimethylsulfonylmethane) in the health functional food code (KFDA notification, standards and standards of health functional foods) according to the Act on Health Functional Foods. Complex extracts including CMO containing FAC (Fatty acid Complex), prickly edible extract, turmeric extract, glucosamine, chicken breast cartilage powder, rose hip powder, boswellia extract, beeswax Alcohols, complexes such as ginseng extract, fatty acid complexes, complex extracts such as perilla, green lipped mussel extract oil, hop extracts, complexes such as golden extracts, and the like. Such compounds or natural extracts may be included in the composition for improving arthritis of the present invention with one or more active ingredients thereof.
본 발명의 관절염 개선용 조성물은 다른 구체적인 양태에 있어서, 식품 조성물로 파악할 수 있다.The composition for arthritis improvement of this invention can be grasped | ascertained as a food composition in another specific aspect.
본 발명의 식품 조성물은 어떠한 형태로도 제조될 수 있으며, 예컨대 차, 쥬스, 탄산음료, 이온음료 등의 음료류, 우유, 요구루트 등의 가공 유류, 껌류, 떡, 한과, 빵, 과자, 면 등의 식품류, 정제, 캡슐, 환, 과립, 액상, 분말, 편상, 페이스트상, 시럽, 겔, 젤리, 바 등의 건강기능식품 제제류 등으로 제조될 수 있다. 또 본 발명의 식품 조성물은 법률상·기능상의 구분에 있어서 제조·유통 시점의 시행 법규에 부합하는 한 임의의 제품 구분을 띨 수 있다. 예컨대 건강기능식품에관한법률에 따른 건강기능식품이거나, 식품위생법의 식품공전(식약처 고시, 식품의 기준 및 규격)상 각 식품유형에 따른 두유류, 발효음료류, 특수용도식품 등일 수 있다.The food composition of the present invention may be prepared in any form, for example, beverages such as tea, juice, carbonated beverages, ionic beverages, processed oils such as milk, yogurt, gums, rice cakes, sweets, bread, sweets, noodles, and the like. It can be prepared as a dietary supplement, such as foods, tablets, capsules, pills, granules, liquid, powder, flaky, paste, syrup, gel, jelly, bar. In addition, the food composition of the present invention can distinguish any product as long as it conforms to the enforcement regulations at the time of manufacture and distribution in the legal and functional divisions. For example, it may be a health functional food according to the Act on Health Functional Foods, or soy milk, fermented beverages, special purpose foods, etc. according to each food type in the Food Code of the Food Sanitation Act (KFDA notice, standards and standards of food).
본 발명의 식품 조성물에는 그 유효성분 이외에 식품첨가물이 포함될 수 있다. 식품첨가물은 일반적으로 식품을 제조, 가공 또는 보존함에 있어 식품에 첨가되어 혼합되거나 침윤되는 물질로서 이해되는데, 식품과 함께 매일 그리고 장기간 복용되므로 그 안전성이 보장되어야 한다. 식품위생법에 따른 식품첨가물공전(식약처 고시, 식품첨가물 기준 및 규격)에는 안전성이 보장된 식품첨가물이 화학적 합성품, 천연 첨가물, 혼합 제제류로 구분하여 한정적으로 규정되어 있다. The food composition of the present invention may include food additives in addition to the active ingredient. Food additives are generally understood as substances that are added to, mixed with, or infiltrated in the manufacture, processing, or preservation of foods, and because they are taken daily with food for a long time, their safety should be ensured. The Food Additives Code of the Food Sanitation Act (KFDA Notification, Food Additives Standards and Standards) defines the food additives that are guaranteed to be safe by dividing them into chemical synthetics, natural additives, and mixed preparations.
이들 식품첨가물은 기능적 측면에 있어서는 감미제, 풍미제, 보존제, 유화제, 산미료, 점증제 등으로 구분될 수 있다. These food additives may be divided into sweeteners, flavors, preservatives, emulsifiers, acidulants, thickeners, and the like in terms of their functionalities.
감미제는 식품이 적당한 단맛을 나게 하는 양으로 사용될 수 있으며, 천연의 것이거나 합성된 것일 수 있다. 바람직하게는 천연 감미제를 사용하는 경우인데, 천연 감미제로서는 옥수수 시럽 고형물, 꿀, 수크로오스, 프룩토오스, 락토오스, 말토오스 등의 당 감미제를 들 수 있다. Sweeteners may be used in amounts that give the food a suitable sweet taste, and may be natural or synthetic. Preferably, a natural sweetener is used. Examples of the natural sweetener include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose and maltose.
풍미제는 맛이나 향을 좋게 하기 위하여 사용될 수 있는데, 천연의 것과 합성된 것 모두 사용될 수 있다. 바람직하게는 천연의 것을 사용하는 경우이다. 천연의 것을 사용할 경우에 풍미 이외에 영양 강화의 목적도 병행할 수 있다. 천연 풍미제로서는 사과, 레몬, 감귤, 포도, 딸기, 복숭아 등에서 얻어진 것이거나 녹차잎, 둥굴레, 대잎, 계피, 국화 잎, 자스민 등에서 얻어진 것일 수 있다. 또 인삼(홍삼), 죽순, 알로에 베라, 은행 등에서 얻어진 것을 사용할 수도 있다. 천연 풍미제는 액상의 농축액이나 고형상의 추출물일 수 있다. 경우에 따라서 합성 풍미제가 사용될 수 있는데, 합성 풍미제는 에스테르, 알콜, 알데하이드, 테르펜 등이 이용될 수 있다. Flavoring agents can be used to enhance the taste or aroma, both natural and synthetic. It is the case of using a natural thing preferably. In addition to flavors, the use of natural ones can be combined with nutritional purposes. The natural flavor may be obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or may be obtained from green tea leaves, round leaves, jujube leaves, cinnamon, chrysanthemum leaves, jasmine and the like. In addition, ginseng (red ginseng), bamboo shoots, aloe vera, ginkgo and the like can also be used. Natural flavors can be liquid concentrates or solid extracts. In some cases, synthetic flavoring agents may be used, and synthetic flavoring agents may include esters, alcohols, aldehydes, terpenes, and the like.
보존제로서는 소듐 소르브산칼슘, 소르브산나트륨, 소르브산칼륨, 벤조산칼슘, 벤조산나트륨, 벤조산칼륨, EDTA(에틸렌디아민테트라아세트산) 등이 사용될 수 있고, 또 유화제로서는 아카시아검, 카르복시메틸셀룰로스, 잔탄검, 펙틴 등을 들 수 있으며, 산미료로서는 연산, 말산, 푸마르산, 아디프산, 인산, 글루콘산, 타르타르산, 아스코르브산, 아세트산, 인산 등이 사용될 수 있다. 산미료는 맛을 증진시키는 목적 이외에 미생물의 증식을 억제할 목적으로 식품 조성물이 적정 산도로 되도록 첨가될 수 있다.Sodium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid) and the like can be used as a preservative, and as an emulsifier, acacia gum, carboxymethylcellulose, xanthan gum, Pectin etc. can be mentioned, As acidic acid, acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, etc. can be used. The acidulant may be added so that the food composition is at an appropriate acidity for the purpose of inhibiting the growth of microorganisms in addition to the purpose of enhancing the taste.
점증제로서는 현탁화 구현제, 침강제, 겔형성제, 팽화제 등이 사용될 수 있다.As the thickener, suspending implementers, sedimenting agents, gel formers, swelling agents and the like can be used.
본 발명의 식품 조성물은 전술한 바의 식품첨가물 이외에, 기능성과 영양성을 보충, 보강할 목적으로 당업계에 공지되고 식품첨가물로서 안정성이 보장된 생리활성 물질이나 미네랄류를 포함할 수 있다.In addition to the food additives described above, the food composition of the present invention may include a bioactive substance or minerals known in the art for the purpose of supplementing and reinforcing the functionality and nutritional properties and ensuring the stability as a food additive.
그러한 생리활성 물질로서는 녹차 등에 포함된 카테킨류, 비타민 B1, 비타민 C, 비타민 E, 비타민 B12 등의 비타민류, 토코페롤, 디벤조일티아민 등을 들 수 있으며, 미네랄류로서는 구연산 칼슘 등의 칼슘 제제, 스테아린산마그네슘 등의 마그네슘 제제, 구연산철 등의 철 제제, 염화 크롬, 요오드칼륨, 셀레늄, 게르마늄, 바나듐, 아연 등을 들 수 있다. Examples of such physiologically active substances include catechins, vitamin B1, vitamin C, vitamin E, vitamin B12 and the like, tocopherol, dibenzoylthiamine and the like contained in green tea, and the like, and calcium minerals such as calcium citrate, magnesium stearate Magnesium preparations such as iron, iron preparations such as iron citrate, chromium chloride, potassium iodine, selenium, germanium, vanadium, zinc and the like.
본 발명의 식품 조성물에는 전술한 바의 식품첨가물이 제품 유형에 따라 그 첨가 목적을 달성할 수 있는 적량으로 포함될 수 있다.In the food composition of the present invention, the food additive as described above may be included in an amount that can achieve the purpose of addition according to the product type.
본 발명의 식품 조성물에 포함될 수 있는 기타의 식품첨가물과 관련하여서는 식품공전이나 식품첨가물 공전을 참조할 수 있다.Regarding other food additives that may be included in the food composition of the present invention, reference may be made to food or food additives.
본 발명의 관절염 개선용 조성물은 구체적인 양태에 있어서, 약제학적 조성물로 파악할 수 있다. The composition for improving arthritis of the present invention can be understood as a pharmaceutical composition in a specific embodiment.
본 발명의 약제학적 조성물은 유효성분 이외에 약제학적으로 허용되는 담체를 포함하여 당업계에 공지된 통상의 방법으로 투여 경로에 따라 경구용 제형 또는 비경구용 제형으로 제조될 수 있다. 여기서 "약제학적으로 허용되는" 의미는 유효성분의 활성을 억제하지 않으면서 적용(처방) 대상이 적응 가능한 이상의 독성을 지니지 않는다는 의미이다.The pharmaceutical compositions of the present invention may be prepared in oral or parenteral formulations according to the route of administration by conventional methods known in the art, including pharmaceutically acceptable carriers in addition to the active ingredient. "Pharmaceutically acceptable" here means that the subject of application (prescription) is not toxic as far as adaptable without inhibiting the activity of the active ingredient.
본 발명의 약제학적 조성물이 경구용 제형으로 제조될 경우, 적합한 담체와 함께 당업계에 공지된 방법에 따라 분말, 과립, 정제, 환제, 당의정제, 캡슐제, 액제, 겔제, 시럽제, 현탁액, 웨이퍼 등의 제형으로 제조될 수 있다. 이때 약제학적으로 허용되는 적합한 담체의 예로서는 락토스, 글루코스, 슈크로스, 덱스트로스, 솔비톨, 만니톨, 자일리톨 등의 당류, 옥수수 전분, 감자 전분, 밀 전분 등의 전분류, 셀룰로오스, 메틸셀룰로오스, 에틸셀룰로오스, 나트륨 카르복시메틸셀룰로오스, 하이드록시프로필메틸셀룰로오스 등의 셀룰로오스류, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 마그네슘 스테아레이트, 광물유, 맥아, 젤라틴, 탈크, 폴리올, 식물성유 등을 들 수 있다. 제제화활 경우 필요에 따라 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 및/또는 부형제를 포함하여 제제화할 수 있다.When the pharmaceutical composition of the present invention is prepared in an oral dosage form, powders, granules, tablets, pills, dragees, capsules, solutions, gels, syrups, suspensions, wafers according to methods known in the art with suitable carriers It may be prepared in a formulation such as. Examples of suitable pharmaceutically acceptable carriers include lactose, glucose, sucrose, dextrose, sugars such as sorbitol, mannitol, xylitol, starch such as corn starch, potato starch, wheat starch, cellulose, methylcellulose, ethylcellulose, Celluloses such as sodium carboxymethylcellulose, hydroxypropylmethylcellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable Yu etc. can be mentioned. If formulated, it may be formulated to include diluents and / or excipients, such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, if necessary.
본 발명의 약제학적 조성물이 비경구용 제형으로 제조될 경우, 적합한 담체와 함께 당업계에 공지된 방법에 따라 주사제, 경피 투여제, 비강 흡입제 및 좌제의 형태로 제제화될 수 있다. 주사제로 제제화활 경우 적합한 담체로서는 멸균수, 에탄올, 글리세롤이나 프로필렌 글리콜 등의 폴리올 또는 이들의 혼합물을 들수 있으며, 바람직하게는 링거 용액, 트리에탄올 아민이 함유된 PBS(phosphate buffered saline)나 주사용 멸균수, 5% 덱스트로스 같은 등장 용액 등을 사용할 수 있다. 경피 투여제로 제제화할 경우 연고제, 크림제, 로션제, 겔제, 외용액제, 파스타제, 리니멘트제, 에어롤제 등의 형태로 제제화될 수 있다. 비강 흡입제의 경우 디클로로플루오로메탄, 트리클로로플루오로메탄, 디클로로테트라플루오로에탄, 이산화탄소 등의 적합한 추진제를 사용하여 에어로졸 스프레이 형태로 제제화될 수 있으며, 좌제의 기제로는 위텝솔(witepsol), 트윈(tween) 61, 폴리에틸렌글리콜류, 카카오지, 라우린지, 폴리옥시에틸렌 소르비탄 지방산 에스테르류, 폴리옥시에틸렌 스테아레이트류, 소르비탄 지방산 에스테르류 등이 사용될 수 있다.When the pharmaceutical compositions of the present invention are prepared in parenteral formulations, they may be formulated in the form of injections, transdermal administrations, nasal inhalants and suppositories with suitable carriers according to methods known in the art. When formulated as an injection, suitable carriers include sterile water, ethanol, polyols such as glycerol or propylene glycol, or mixtures thereof. Preferably, PBS (phosphate buffered saline) containing Ringer's solution or triethanol amine or sterile water for injection , Isotonic solutions such as 5% dextrose, and the like can be used. When formulated as a transdermal administration, it may be formulated in the form of an ointment, cream, lotion, gel, external solution, pasta, linen, aerosol and the like. Nasal inhalants can be formulated in the form of aerosol sprays using suitable propellants such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc. The bases of suppositories are witepsol, twin (tween) 61, polyethylene glycols, cacao butter, laurin paper, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearate, sorbitan fatty acid esters and the like can be used.
약제학적 조성물의 제제화와 관련하여서는 당업계에 공지되어 있으며, 구체적으로 문헌[Remington's Pharmaceutical Sciences(19th ed., 1995)] 등을 참조할 수 있다. 상기 문헌은 본 명세서의 일부로서 간주 된다.Regarding the formulation of pharmaceutical compositions, it is known in the art and specific reference may be made to Remington's Pharmaceutical Sciences (19th ed., 1995) and the like. The document is considered part of this specification.
본 발명의 약제학적 조성물의 바람직한 투여량은 환자의 상태, 체중, 성별, 연령, 환자의 중증도, 투여 경로에 따라 1일 0.001mg/kg ~ 10g/kg 범위, 바람직하게는 0.001mg/kg ~ 1g/kg 범위일 수 있다. 투여는 1일 1회 또는 수회로 나누어 이루어질 수 있다. 이러한 투여량은 어떠한 측면으로든 본 발명의 범위를 제한하는 것으로 해석되어서는 아니 된다. Preferred dosages of the pharmaceutical compositions of the present invention range from 0.001 mg / kg to 10 g / kg per day, preferably 0.001 mg / kg to 1 g, depending on the condition, body weight, sex, age, severity of the patient and route of administration. It can range from / kg. Administration can be done once a day or divided into several times. Such dosage should not be construed as limiting the scope of the invention in any aspect.
본 발명은 다른 측면에 있어서, 좁은잎천선과 잎 추출물을 유효성분으로 포함하는 만성통증 개선용 조성물을 제공한다. 본 발명의 만성통증 개선용 조성물의 유효성분, 그 식품 또는 약품 조성물로의 적용 양태 등과 관련하여서는 본 발명의 관절염 개선용 조성물에 대해 전술한 바가 그대로 준용될 수 있다. In another aspect, the present invention provides a composition for improving chronic pain, including narrow leaf zenith and leaf extract as an active ingredient. With respect to the active ingredient of the composition for improving chronic pain of the present invention, the aspect of application to the food or drug composition, etc., the above-described bar may be applied mutatis mutandis to the composition for improving arthritis of the present invention.
전술한 바와 같이, 본 발명에 따르면 좁은잎천선과 잎 추출물을 이용한 관절염 개선용 조성물을 제공할 수 있다. 본 발명의 관절염 개선용 조성물은 기능성 식품, 약품 등으로 제품화될 수 있다.As described above, according to the present invention can provide a composition for improving arthritis using a narrow leaf zenith and leaf extract. The composition for improving arthritis of the present invention can be commercialized as a functional food, drugs and the like.
도 1과 2는 각각 MIA 유도 골관절염 동물모델에서 주차별 체중 변화와 주차별 행동 변화를 나타낸 결과이다.
도 3 내지 5는 MIA 유도 골관절염 동물모델에서 염증성 사이토카인(IL-1β, TNF-α, IL-6)을 측정한 결과이다.
도 6 내지 12는 MIA 유도 골관절염 비임상 동물모델에서 MMP-2, 3, 4, 9, 13과 TIMP-1, 2의 mRNA 발현 정도를 Real-Time PCR를 통하여 확인한 결과이다.
도 13은 MIA에 의한 골관절염 모델에서 실험동물 연골조직 H&E 염색 결과이다.
도 14는 만성통증 동물실험 결과이다. 1 and 2 are the results showing the changes in weight and parking behavior by parking in MIA induced osteoarthritis animal model, respectively.
3 to 5 are the results of measuring the inflammatory cytokines (IL-1β, TNF-α, IL-6) in MIA induced osteoarthritis animal model.
6 to 12 are the results of confirming the mRNA expression levels of MMP-2, 3, 4, 9, 13 and TIMP-1, 2 in MIA-induced osteoarthritis nonclinical animal model by real-time PCR.
13 shows the results of H & E staining of experimental animal cartilage tissue in a osteoarthritis model by MIA.
14 is a chronic pain animal experiment results.
이하 본 발명을 실시예 및 실험예를 참조하여 설명한다. 그러나 본 발명의 범위가 이러한 실시예 및 실험예에 한정되는 것은 아니다.Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these examples and experimental examples.
<< 실시예Example > > 좁은잎천선과 잎 추출물의 제조Preparation of Narrow Leaf Lines and Leaf Extracts
좁은잎천선과 잎을 건조 분쇄하여 20배 중량의 70% 에탄올에 침지시킨 후, 18시간 동안 실온에서 교반 시켜 추출하고 여과한 후 그 여액을 감압 농축하고 동결건조하여 분말상의 추출물을 얻었다. 이렇게 얻어진 추출물을 냉장보관하면서 아래의 동물실험에 사용하였다.Narrow leaf zenith and leaves were dried and pulverized, immersed in 20% of 70% ethanol, stirred for 18 hours at room temperature, extracted and filtered. The filtrate was concentrated under reduced pressure and lyophilized to obtain a powdery extract. The extract thus obtained was used in the animal experiment below while refrigerated.
<< 실험예Experimental Example > > MIA(monosodium MIA (monosodium iodoacetateiodoacetate )에 의한 골관절염 동물실험과 만성 통증 동물실험 Osteoarthritis Animal Experiment and Chronic Pain Animal Experiment
<실험예 1> Experimental Example 1 MIA(monosodium iodoacetate)에 의한 골관절염 동물실험Osteoarthritis Animal Experiment by MIA (monosodium iodoacetate)
1. 실험 방법1. Experiment Method
(1) MIA에 의한 골관절염 유도(1) Induction of Osteoarthritis by MIA
약물 유도 모델은 실험동물에 특정 약물을 intra-articular injection 등의 방법으로 주입하여 chondrocyte의 metabolism을 저해하거나, ligament와 tendon의 손상을 유발함으로서 골관절염을 발생시키는 방법으로, 본 실험에서는 MIA (monosodium iodoacetate)를 사용하여 골관절염을 유발시켰다.Drug-induced model is a method to induce osteoarthritis by injecting a specific drug into the experimental animal by intra-articular injection, etc. to inhibit the metabolism of chondrocytes or damage ligament and tendon.In this experiment, MIA (monosodium iodoacetate) Was used to cause osteoarthritis.
무릎주변을 깨끗이 제모한 후 골관절염 유발물질인 MIA(Monosodium iodoacetate)를 1 mL 주사기를 사용하여 오른쪽 무릎 관절강 내에 50 ㎕ (60 mg/mL)씩 투여하였다. MIA 희석시에는 0.9 % saline을 사용하였다. MIA 투여 7일 후에 골관절염 유발 유무를 확인하여 골관절염이 유발된 동물만을 실험에 사용하였다.After cleansing the area around the knee, 50 μl (60 mg / mL) of osteoarthritis-inducing substance MIA (Monosodium iodoacetate) was administered to the right knee joint cavity using a 1 mL syringe. When diluting MIA, 0.9% saline was used. After 7 days of MIA administration, the presence of osteoarthritis was confirmed, and only animals with osteoarthritis were used in the experiment.
(2) 시험물질 투여와 체중 측정, 주차별 행동 변화 측정(2) Test substance administration, weight measurement, and behavior change by parking
1주일에 1회 체중을 측정하고 주차별 행동 score를 측정하였다. 시험물질인 실시예의 좁은잎천선과 잎 추출물(FES, 투여량 250, 500 mg/kg)은 실험 기간 동안 매일 오전 투여, 측정은 오후에 하는 것을 원칙으로 하였다. 측정일은 시험물질을 사료에 혼합하여 경구투여한 후 7, 14, 21일째 되는 날에 각각 시행하였다. 양성대조군은 비스테로이드성 약물(NSAID)의 일종인 인도메타신(indomethacin)을 사용하였다.Body weights were measured once a week and behavioral scores were measured by parking. Narrow leaf zenith and leaf extract (FES,
(3) 생물학적 지표 검사(3) biological indicator testing
투여 전과 후 또는 전체 투여기간에 걸쳐 일정한 간격을 두고 혈액 및 synovial fluid를 채취하였다. 혈액으로부터 혈청 또는 혈장을 분리한 뒤, 염증성 지표로서 IL-1β, TNF-α, IL-6 등의 사이토카인은 ELISA로 측정하였다. 그리고 연골조직의 파괴 정도를 확인하기 위해 synovial fluid를 이용하여 MMP-2, 3, 7, 9, 13 및 TIMP-1, 2 등의 발현을 측정하였다. 투여가 완료된 후에는 실험동물의 사체로부터 synovial tissue를 채취하여 RNA를 분리하여 아래 [표 1]의 프라이머를 사용하여 PCR 등의 방법을 통해 MMP-2, 3, 7, 9, 13 및 TIMP-1, 2 등의 mRNA 발현정도를 분석하였다. 구체적으로 Rat의 조직으로부터 추출한 total RNA는 TRI-reagent(MRC, Cincinnati, OH, USA)를 이용하였으며, RNase-free한 조건하에서 이루어졌다. 1 ㎍의 total RNA를 oligo (dT) 18 primer, dNTP (0.5 μM), 1 unit RNase inhibitor 그리고 M-MuLV reverse transcriptase (2U)로 70℃ 5 min, 25℃ 5 min, 37℃ 60 min, 그리고 70℃에서 10 min 간 heating 시킴으로서 cDNA를 합성하였다. Quantitative real-time polymerase chain reaction (qRT-PCR)을 위해, 2 ㎕의 cDNA, 12.5 ㎕의 master mix [SYBR premix Ex Taq II (Takara, Japan)], 1 ㎕의 각각의 primer (표 1), 8.5 ㎕의 DW를 혼합한 후 MX3005P (Stratagene, USA)을 이용하여 실시간으로 각 유전자의 발현양상을 측정하였다. 이때 PCR cycle은 95℃에서 10분 후, 95℃/15초와 60℃/60초를 40 cycle 동안 반복하였으며, 각각의 측정된 유전자들의 cycle threshold (CT)는 대조군과 비교하여 발현량을 산출하였다.Blood and synovial fluid were collected before and after dosing or at regular intervals throughout the dosing period. After separating serum or plasma from blood, cytokines such as IL-1β, TNF-α, IL-6 as inflammatory markers were measured by ELISA. In addition, the expression of MMP-2, 3, 7, 9, 13 and TIMP-1, 2 was measured using synovial fluid to confirm the degree of cartilage destruction. After the administration is completed, the synovial tissue is collected from the corpse of the experimental animal, RNA is isolated, and MMP-2, 3, 7, 9, 13 and TIMP-1 by PCR or the like using the primers shown in Table 1 below. , MRNA expression levels of 2 and the like were analyzed. Specifically, total RNA extracted from rat tissue was used TRI-reagent (MRC, Cincinnati, OH, USA), and was made under RNase-free conditions. 1 μg total RNA was added with oligo (dT) 18 primer, dNTP (0.5 μM), 1 unit RNase inhibitor and M-MuLV reverse transcriptase (2U) at 70 ° C 5 min, 25 ° C 5 min, 37 °
(4) 실험동물 연골조직 H&E 염색(4) H & E staining of experimental animal cartilage tissue
실험 종료 후 rat을 희생하여 병리조직학적 관찰을 위해 슬관절을 채취하였다. 슬관절의 고정을 위해 적출 즉시 10% formaldehyde (Junsei, Tokyo, Japan)로 24시간 고정하였고, Calci-Clear Rapid(National Diagnostics, Atlanta, GA, USA)로 24시간 간격으로 72시간 동안 용액을 교환하면서 탈회를 실시하였다. 파라핀 블록의 제작과 냉각은 자동 포매장치 (Tissue-Tex 4701, Sakura Co., Tokyo, Japan)를 사용하였다. 제작된 블록은 회전식 미세박절기 (rotary michrotome 2040, Sakura Co.)를 사용하여 조직을 수직방향으로 7m 두께로 연속 절편하여, 부유 온수조와 신전기 과정을 거쳐 슬라이드에 부착시켰다. 제작된 조직 슬라이드는 염증성 침윤 정도를 평가하기 위해 Hematoxylin & Eosin (H&E) 염색을 실시하였다. After the experiment, the rats were sacrificed and the knee joints were collected for histopathological observation. Immediately after extraction for fixation of the knee joint, it was fixed for 24 hours with 10% formaldehyde (Junsei, Tokyo, Japan) and demineralized by exchanging solution for 72 hours at 24-hour intervals with Calci-Clear Rapid (National Diagnostics, Atlanta, GA, USA). Was carried out. The fabrication and cooling of paraffin blocks were performed using an automatic embedding device (Tissue-Tex 4701, Sakura Co., Tokyo, Japan). The fabricated block was sequentially sliced into 7 m thick tissue in a vertical direction using a rotary michrotome 2040 (Sakura Co.), and attached to the slide through a floating hot water bath and an extension process. The prepared tissue slides were subjected to Hematoxylin & Eosin (H & E) staining to evaluate the degree of inflammatory infiltration.
2. 실험 결과2. Experimental Results
(1) MIA에 의한 골관절염 모델에서 체중 변화 및 (1) weight change in osteoarthritis model by MIA and 주차별By parking 행동 결과 Action result
MIA 유도 골관절염 모델에서의 주차별 체중 변화를 [도 1]에, MIA 유도 골관절염 모델에서의 주차별 행동 변화를 [도 2]에 나타내었다. Parking weight change in the MIA-induced osteoarthritis model is shown in FIG. 1, and parking change in the MIA-induced osteoarthritis model is shown in FIG.
MIA에 의해 골관절염이 유발된 모델에서 매주 주차별 체중 변화를 측정한 결과, 모든 군에서 체중의 증가가 관찰되었으나 체중 변화의 차이는 관찰되지 않았다.In the model of osteoarthritis induced by MIA, weekly weight change was observed in all groups, but there was no difference in body weight.
또 아래 [표 2]의 기준으로 주차별 행동 변화를 측정한 결과, 주차별 행동 score가 시험물질 투여군에서 MIA만 처리한 관절염 유발 모델 처리군(MIAC)에 비해 1주차부터 감소하기 시작하여 3주차에는 양성대조군인 인도메타신(IM)보다도 더 낮은 수준으로 감소하였다(p<0.05). As a result of measuring the change of behavior by parking according to the criteria of [Table 2] below, the behavioral score by parking began to decrease from
(2) MIA에 의한 골관절염 모델에서 생화학적 지표 변화(2) Biochemical Indicator Changes in the Osteoarthritis Model by MIA
MIA에 인해 유발된 골관절염 모델에서 생화학적 지표 변화를 확인하기 위해 투여 전 후에 걸쳐 혈액 및 synovial fluid를 채취하였다. 혈액으로부터 혈청 또는 혈장을 분리한 뒤, 염증성 지표로서 IL-1β, TNF-α, IL-6 등의 사이토카인을 ELISA assay kit를 사용하여 측정하여 결과를 [도 3 내지 5]에 나타내었다. 좁은잎천선과 잎 추출물을 투여한 결과 MIA만 처리한 골관절염 유발 모델(MIAC)에 비해 농도 의존적으로 염증성 지표 물질들의 생성을 억제하는 것을 확인하였다.Blood and synovial fluids were collected before and after administration to confirm biochemical marker changes in the MIA-induced osteoarthritis model. After separating serum or plasma from blood, cytokines such as IL-1β, TNF-α, IL-6 as inflammatory markers were measured using an ELISA assay kit, and the results are shown in FIGS. 3 to 5. As a result of the administration of the narrow leaf zenith and leaf extract, it was confirmed that the inhibition of the production of inflammatory markers in a concentration-dependent manner compared to the MIA-treated osteoarthritis-induced model (MIAC).
(3) MIA에 의한 골관절염 모델의 연골조직에서 생화학적 지표 변화(3) Biochemical Indicators in Cartilage Tissue in Osteoarthritis Model by MIA
MIA에 인해 유발된 골관절염 모델에서 생화학적 지표 변화를 확인하기 위해 투여 완료 후 연골조직을 분리하여 골 및 연골의 기지 구성요소를 파괴하는 생화학적 지표인 MMP-2, 3, 7, 9, 13과 TIMP-1, 2에 대한 mRNA 발현 정도를 Real-Time PCR를 통하여 확인하여 결과를 [도 6 내지 12]에 나타내었다. 좁은잎천선과 잎 추출물을 투여한 결과 MIA만 처리한 골관절염 유발 모델(MIAC)에 비해 모든 생화학적 지표에 있어서 mRNA 발현을 농도 의존적으로 뚜렷하게 억제하는 것을 확인하였다.MMP-2, 3, 7, 9, 13, and biochemical indicators that break down cartilage and destroy the matrix components of bone and cartilage after completion of administration to confirm biochemical marker changes in MIA-induced osteoarthritis models. MRNA expression level for TIMP-1, 2 was confirmed by real-time PCR, and the results are shown in [FIGS. 6 to 12]. As a result of the administration of the narrow leaf zenith and leaf extract, it was confirmed that the mRNA expression was significantly inhibited in all biochemical markers compared to the MIA-treated osteoarthritis-induced model (MIAC).
(4) MIA에 의한 골관절염 모델에서 실험동물 연골조직 H&E 염색(4) H & E staining of experimental animal cartilage tissue in MIA osteoarthritis model
좁은잎천선과 잎 추출물이 무릎 관절 및 연골 조직에 미치는 영향을 확인하기 위하여 H&E stain을 실시하여 결과를 [도 13], MIA만 처리한 골관절염 유도 모델(MIAC)에서는 골관절염이 유발되어 정상군보다 연골과 활막 및 섬유조직의 변형이 현저하게 나타난 반면, 좁은잎천선과 추출물 투여군은 정상군과 비슷하게 회복되는 것을 확인하였다.In order to confirm the effect of the narrow leaf pericardium and leaf extract on the knee joint and cartilage tissue, the results of H & E staining were performed [FIG. 13], and osteoarthritis was induced in the MIA-only osteoarthritis induction model (MIAC). The synovial and fibrous tissues were remarkably deformed, whereas the narrow leaf periphery and extract-treated group recovered similarly to the normal group.
<실험예 2> 만성통증 동물실험 - Formalin testExperimental Example 2 chronic pain animal experiment-Formalin test
1. 실험 방법 - Formalin test1. Experimental Method-Formalin test
Formalin test는 유해 자극에 대한 조직손상이 일어나는 지속적인 통증에 대한 효력 시험방법으로 통증 자극이 지속적인 만성 통증 모델이다. rat의 뒷발에 10% Formalin을 피하 주사한 뒤 3분 단위로 투여한 발의 Flinching 행동 수를 측정하였다. Flinching 행동은 Phase 1 (0-12 분)과 Phase 2 (24-39 분)으로 나누며, Phase 1 시기에는 침해 자극에 의한 구심성 C 섬유의 흥분에 따른 급성 통증 행동으로 formalin 투여 후 5-10분간 지속되었다가 사라진다. Phase 2는 염증 관련 물질 즉 프로스타글라딘 등에 의하여 야기되어지는 말초 신경계 관련 통증 및 중추신경 감작에 의한 복합성 통증을 측정하는데, 통증반응은 20-60분에 걸쳐 보인다. formalin 주사 후 나타나는 초기의 통증반응은 통각수용체에 대한 직접적인 자극 때문이고 후기에 보이는 통증반응은 중추성 감작 때문이다. 좁은잎천선과 추출물을 각각 250 mg/kg, 500 mg/kg로 실험 시작 60분 전에 경구 투여하였다.Formalin test is a test for the effects of persistent pain in tissue damage against harmful stimuli. The number of flinching behaviors of the paws administered in 3 minutes after subcutaneous injection of 10% formalin into the hind paws of rats was measured. Flinching behavior is divided into Phase 1 (0-12 minutes) and Phase 2 (24-39 minutes) .At the first phase, 5-10 minutes after formalin administration as acute pain behavior due to afferent C-fiber excitation caused by invasive stimulation. It continues and disappears.
2. 실험 결과2. Experimental Results
결과를 [도 14]에 나타내었다. [도 14]을 참조하여 보면, Phase 1에서는 500 mg/kg에서 대조군에 비해 크게 억제되는 것을 확인하였으며, Phase 2에서는 좁은잎천선과 추출물 투여군 모두에서 대조군에 비해 크게 억제된 것을 알 수 있다(p<0.05).The results are shown in [FIG. 14]. Referring to FIG. 14, it was confirmed that
Claims (8)
Arthritis improving composition comprising a narrow leaf zenith and leaf extract as an active ingredient.
상기 추출물은 좁은잎천선과 잎을 물, 에탄올, 또는 이들의 혼합 용매로 추출하여 얻어진 것을 특징으로 하는 관절염 개선용 조성물.
The method of claim 1,
The extract is a composition for improving arthritis, characterized in that obtained by extracting the narrow leaf zenith and leaves with water, ethanol, or a mixed solvent thereof.
상기 관절염은 골관절염 또는 류마티스 관절염인 것을 특징을 하는 관절염 개선용 조성물.
The method of claim 1,
The arthritis is a composition for improving arthritis, characterized in that the osteoarthritis or rheumatoid arthritis.
상기 조성물은 식품 조성물인 것을 특징으로 하는 관절염 개선용 조성물.
The method according to any one of claims 1 to 3,
The composition is an arthritis improving composition, characterized in that the food composition.
상기 조성물은 약제학적 조성물인 것을 특징으로 하는 관절염 개선용 조성물.
The method according to any one of claims 1 to 3,
The composition is a composition for improving arthritis, characterized in that the pharmaceutical composition.
Analgesic composition comprising a narrow leaf zenith and leaf extract as an active ingredient.
상기 조성물은 식품 조성물인 것을 특징으로 하는 진통용 조성물.
The method of claim 6,
The composition for analgesic, characterized in that the food composition.
상기 조성물은 약제학적 조성물인 것을 특징으로 하는 진통용 조성물.
The method of claim 6,
The composition for analgesic, characterized in that the pharmaceutical composition.
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KR20220053233A (en) * | 2020-10-22 | 2022-04-29 | 주식회사 하람 | A composition for immune enhancement comprising narrow-leaf erecta fig extract |
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KR101583591B1 (en) * | 2012-07-26 | 2016-01-12 | 재단법인 제주테크노파크 | Anti-inflammatory Composition Using a Extract of Ficus erecta Leaf |
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KR101583591B1 (en) * | 2012-07-26 | 2016-01-12 | 재단법인 제주테크노파크 | Anti-inflammatory Composition Using a Extract of Ficus erecta Leaf |
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