KR20230105651A - Composition for prevention, improvement or treatment of arthritis and joint pain comprising Hieracium umbellatum extract as effective component - Google Patents
Composition for prevention, improvement or treatment of arthritis and joint pain comprising Hieracium umbellatum extract as effective component Download PDFInfo
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- KR20230105651A KR20230105651A KR1020220180489A KR20220180489A KR20230105651A KR 20230105651 A KR20230105651 A KR 20230105651A KR 1020220180489 A KR1020220180489 A KR 1020220180489A KR 20220180489 A KR20220180489 A KR 20220180489A KR 20230105651 A KR20230105651 A KR 20230105651A
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Abstract
본 발명은 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방, 개선 또는 치료용 조성물에 관한 것으로, 본 발명의 조밥나물 추출물은 연골기질 분해효소인 MMP-1(Matrix metalloproteinase-1) 및 MMP-13(Matrix metalloproteinase-13)의 발현을 저해하고, 연골 프로테오글리칸(Proteoglycan) 분해 산물인 GAG(Glycosaminoglycan)의 함량을 감소시키며, 통증이 유발된 동물모델에서 진통효과를 나타내고, 염증으로 인한 부종을 완화시키는 효과가 있으므로, 관절염 및 관절통증의 예방, 개선 또는 치료용 건강기능식품 또는 의약품 등에 매우 유용하게 사용될 수 있다. The present invention relates to a composition for preventing, improving or treating arthritis and joint pain containing an extract of millet sprouts as an active ingredient. It inhibits the expression of MMP-13 (Matrix metalloproteinase-13), reduces the content of GAG (Glycosaminoglycan), a product of cartilage proteoglycan degradation, exhibits analgesic effects in pain-induced animal models, and reduces swelling caused by inflammation. Since it has an alleviating effect, it can be very usefully used in health functional foods or pharmaceuticals for the prevention, improvement or treatment of arthritis and joint pain.
Description
본 발명은 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방, 개선 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prevention, improvement or treatment of arthritis and joint pain, containing a millet sprouts extract as an active ingredient.
노령화 사회로 접어들면서 관절염을 포함하는 염증성 질환이 성별에 상관없이 사회적으로 대두되고 있다. 이러한 염증반응에 의해 발생하는 염증성 질환에는 위염, 대장염, 관절염, 신장염, 간염, 동맥경화, 암 또는 퇴행성 질환 등이 포함된다. 그 중 현재까지 관절염 질환의 예방 및 치료를 위한 효과적인 약제나 치료법은 개발되지 못하고 있다. 관절염은 노화, 기계적 손상, 면역이상 등 다양한 원인에 의해 관절 내에 염증성 변화가 생긴 것을 지칭한다.As we enter an aging society, inflammatory diseases including arthritis are socially emerging regardless of gender. Inflammatory diseases caused by this inflammatory response include gastritis, colitis, arthritis, nephritis, hepatitis, arteriosclerosis, cancer, or degenerative diseases. Among them, effective drugs or treatments for the prevention and treatment of arthritis diseases have not been developed so far. Arthritis refers to an inflammatory change in a joint due to various causes such as aging, mechanical damage, and immune abnormality.
상기한 관절염 중에서, 골관절염(osteoarthritis)은 퇴행성 관절염으로 칭해지기도 하는 관절염의 일종으로서, 윤활 관절에서 연골과 주위골에 퇴행성 변화가 나타나서 생기는 관절염을 말한다. 즉, 골관절염은 관절 연골의 점차적인 소실과 더불어 연골 하방에 위치한 뼈의 비대, 관절 가장자리 부위의 골 생성, 및 비특이적인 활막 염증을 특징으로 하는 질환이다. 골관절염은 노화나 과도한 물리적 압박(예를 들어, 비만, 외상 등)에 의해서 연골이 손상되어 발생하는 질환이다. 따라서, 골관절염은 체중을 많이 받는 관절, 즉, 무릎(슬)관절, 엉덩이 (고)관절 등에 심한 통증과 운동 장애를 나타내며, 장기간 방치할 경우에는 관절의 변형까지 초래하게 된다.Among the above-mentioned arthritis, osteoarthritis (osteoarthritis) is a kind of arthritis, also called degenerative arthritis, refers to arthritis caused by degenerative changes in cartilage and surrounding bones in synovial joints. That is, osteoarthritis is a disease characterized by gradual loss of articular cartilage, hypertrophy of bones located below the cartilage, bone formation at the joint edge, and non-specific synovial inflammation. Osteoarthritis is a disease caused by damage to cartilage due to aging or excessive physical pressure (eg, obesity, trauma, etc.). Therefore, osteoarthritis shows severe pain and movement disorders in joints that receive a lot of weight, that is, knee (knee) joints, hip (hip) joints, etc., and even causes deformation of the joints when left unattended for a long period of time.
또한, 통풍성 관절염은 관절 내 공간과 조직에 요산이 침착되면서 발생하는 염증으로, 혈액 내에 요산(음식을 통해 섭취되는 퓨린(purine)이라는 물질을 인체가 대사하고 남은 산물)의 농도가 높아지면서 요산염(요산이 혈액, 체액, 관절액 내에서는 요산염의 형태 존재함) 결정이 관절의 연골, 힘줄, 주위 조직에 침착되는 질병이다. 이러한 현상은 관절의 염증을 유발하여 극심한 통증을 동반하는 재발성 발작을 일으킨다.In addition, gouty arthritis is an inflammation caused by the deposition of uric acid in the space and tissues within the joint. As the concentration of uric acid (a product left after the body metabolizes a substance called purine consumed through food) increases, the uric acid (Uric acid exists in the form of uric acid in blood, body fluids, and joint fluid.) It is a disease in which crystals are deposited in joint cartilage, tendons, and surrounding tissues. This phenomenon causes inflammation of the joint, resulting in recurrent attacks with excruciating pain.
한편, 조밥나물(Hieracium umbellatum L.)은 국화과(Compositae)의 식물로서 높이 60~90㎝에 이르는 여러해 살이풀이다. 잎은 버들모양이고 톱니가 성글게 있다. 여름철에 노란꽃이 핀다. 각지의 산과 들에서 자란다. 성분으로는 전초에 이눌린, 탄닌질, 잎에 아스코르빈산이 있다. 어린 잎은 산나물로 먹으며 생약명으로는 산류국이라고 불리우며, 중약에서는 종독을 치료하는데 사용한다.On the other hand, rice plants ( Hieracium umbellatum L. ) is a plant of the Asteraceae family (Compositae) and is a perennial herb reaching 60 to 90 cm in height. The leaves are willow-shaped and have sparse sawtooth. Yellow flowers bloom in summer. It grows in mountains and fields all over the place. Ingredients include inulin, tannin in the outpost, and ascorbic acid in the leaves. The young leaves are eaten as wild vegetables, and the herbal medicine name is called Sanryuguk, and in Chinese medicine, it is used to treat poisoning.
한편, 한국등록특허 제1380970호에는 '생약 추출물을 포함하는 관절염 예방 또는 치료용 및 항혈액암제용 약학적 조성물'에 대해 개시하고 있으며, 한국공개특허 제2008-0106770호에는 '천연생약 추출물을 함유하는 관절염 예방 및 치료용 조성물'에 대해 개시하고 있다. 하지만, 본 발명의 '조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방, 개선 또는 치료용 조성물'에 대해서는 아직까지 개시된 바가 없다.Meanwhile, Korean Registered Patent No. 1380970 discloses a 'pharmaceutical composition for preventing or treating arthritis and for anti-hemorrhagic agents containing a herbal medicine extract', and Korean Patent Publication No. 2008-0106770 'contains a natural herbal medicine extract'. A composition for preventing and treating arthritis' is disclosed. However, the 'composition for preventing, improving or treating arthritis and joint pain containing the extract of millet sprouts as an active ingredient' of the present invention has not been disclosed yet.
본 발명은 상기와 같은 요구에 의해 도출된 것으로서, 본 발명은 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방, 개선 또는 치료용 조성물을 제공하고, 본 발명의 조밥나물 추출물은 연골기질 분해효소인 MMP-1(Matrix metalloproteinase-1) 및 MMP-13(Matrix metalloproteinase-13)의 발현을 저해하고, 연골 프로테오글리칸(Proteoglycan) 분해 산물인 GAG(Glycosaminoglycan)의 함량을 감소시키며, 통증이 유발된 동물모델에서 진통효과를 나타내고, 염증으로 인한 부종을 완화시키는 효과가 있다는 것을 확인함으로써, 본 발명을 완성하였다.The present invention has been derived from the above needs, and the present invention provides a composition for the prevention, improvement or treatment of arthritis and joint pain containing a millet sprouts extract as an active ingredient, and the millet sprouts extract of the present invention is a cartilage matrix. It inhibits the expression of MMP-1 (Matrix metalloproteinase-1) and MMP-13 (Matrix metalloproteinase-13), which are degrading enzymes, reduces the content of GAG (Glycosaminoglycan), a product of cartilage proteoglycan degradation, The present invention was completed by confirming that the analgesic effect was shown in an animal model and that there was an effect of alleviating edema due to inflammation.
상기 목적을 달성하기 위하여, 본 발명은 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In order to achieve the above object, the present invention provides a health functional food composition for preventing or alleviating arthritis and joint pain, containing an extract of millet sprouts as an active ingredient.
또한, 본 발명은 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방 또는 치료용 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of arthritis and joint pain containing the extract of millet sprouts as an active ingredient.
또한, 본 발명은 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방 또는 개선용 사료 첨가제를 제공한다.In addition, the present invention provides a feed additive for preventing or improving arthritis and joint pain, containing the extract of millet sprouts as an active ingredient.
또한, 본 발명은 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방 또는 치료용 수의학적 조성물을 제공한다.In addition, the present invention provides a veterinary composition for the prevention or treatment of arthritis and joint pain containing the extract of millet sprouts as an active ingredient.
본 발명은 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방, 개선 또는 치료용 조성물에 관한 것으로, 본 발명의 조밥나물 추출물은 연골기질 분해효소인 MMP-1(Matrix metalloproteinase-1) 및 MMP-13(Matrix metalloproteinase-13)의 발현을 저해하고, 연골 프로테오글리칸(Proteoglycan) 분해 산물인 GAG(Glycosaminoglycan)의 함량을 감소시키며, 통증이 유발된 동물모델에서 진통효과를 나타내고, 염증으로 인한 부종을 완화시키는 효과가 있다.The present invention relates to a composition for preventing, improving or treating arthritis and joint pain containing an extract of millet sprouts as an active ingredient. It inhibits the expression of MMP-13 (Matrix metalloproteinase-13), reduces the content of GAG (Glycosaminoglycan), a product of cartilage proteoglycan degradation, exhibits analgesic effects in pain-induced animal models, and reduces swelling caused by inflammation. has a mitigating effect.
도 1은 본 발명의 조밥나물 추출물의 처리에 따른 MMP-1 및 MMP-13의 함량 변화를 확인한 결과이다. ####은 아무것도 처리하지 않은 대조군(Con) 대비 IL-1β 처리군의 MMP-1 및 MMP-13 함량이 유의미하게 증가하였다는 것으로, p<0.0001이다. ****은 IL-1β 처리군 대비 본 발명의 조밥나물 추출물 처리군의 MMP-1 또는 MMP-13 함량이 유의미하게 감소하였다는 것으로, p<0.0001이다.
도 2는 본 발명의 조밥나물 추출물의 처리에 따른 GAG 함량 변화를 확인한 결과이다. ##은 아무것도 처리하지 않은 대조군(Con) 대비 IL-1β 처리군의 GAG 함량이 유의미하게 증가하였다는 것으로, p<0.01이다. **은 IL-1β 처리군 대비 본 발명의 조밥나물 추출물 처리군의 GAG 함량이 유의미하게 감소하였다는 것으로, p<0.01이다.
도 3은 아세트산 유도에 의한 통증 유발 동물모델에서, 본 발명의 조밥나물 추출물의 투여에 따른 진통 효과를 확인한 결과이다. 대조군(con)은 아세트산(10㎖/kg) 복강투여로 인해 통증을 유도한 군이고, PC는 양성대조군으로, 디클로페낙(10mg/kg)을 투여한 군이다. **, ***은 아세트산 복강투여로 인해 통증을 유도한 대조군(con) 대비 양성대조군(PC) 또는 본 발명의 조밥나물 추출물(150mg/kg 및 300mg/kg)을 투여한 실험군이 10분 동안 몸을 뒤트는 횟수가 유의미하게 감소하였다는 것으로, **은 p<0.01이고, ***은 p<0.001이다.
도 4는 카라기난에 의한 염증 유발 동물모델에서, 조밥나물 추출물 투여에 따른 족부 부종 완화 효과를 확인한 결과이다. 대조군(con)은 카라기난만을 투여한 군이고, PC는 양성대조군으로, 인도메타신(5mg/kg)을 투여한 군이다. *, **, ****은 카라기난 단독 투여군(con) 대비 양성대조군 또는 조밥나물 추출물 투여군의 족부 부종이 유의미하게 감소하였다는 것으로, *은 p<0.05이고, **은 p<0.01이고, ****은 p<0.0001이다. 1 is a result of confirming the change in the contents of MMP-1 and MMP-13 according to the treatment of the millet sprouts extract of the present invention. #### indicates that the MMP-1 and MMP-13 contents of the IL-1β treated group were significantly increased compared to the untreated control group (Con), p<0.0001. **** means that the MMP-1 or MMP-13 content of the millet greens extract treatment group of the present invention was significantly decreased compared to the IL-1β treatment group, p<0.0001.
Figure 2 is the result of confirming the change in GAG content according to the treatment of the millet sprouts extract of the present invention. ## indicates that the GAG content of the IL-1β treated group was significantly increased compared to the control group (Con) not treated with anything, p<0.01. ** means that the GAG content of the millet greens extract treatment group of the present invention significantly decreased compared to the IL-1β treatment group, p <0.01.
Figure 3 is a result of confirming the analgesic effect according to the administration of the herbaceous plant extract of the present invention in an animal model of pain induction by acetic acid induction. The control group (con) was a group in which pain was induced by intraperitoneal administration of acetic acid (10 ml/kg), and the PC was a positive control group and was administered with diclofenac (10 mg/kg). **, *** indicate that the control group (con) inducing pain due to intraperitoneal administration of acetic acid compared to the positive control group (PC) or the experimental group administered with the rice plant extract (150mg/kg and 300mg/kg) of the present invention for 10 minutes The number of body twists was significantly reduced, ** is p<0.01, and *** is p<0.001.
Figure 4 is the result of confirming the foot edema relief effect according to the administration of the herbaceous plant extract in an animal model inducing inflammation by carrageenan. The control group (con) is a group administered only with carrageenan, and the PC is a positive control group, which is a group administered with indomethacin (5 mg/kg). *, **, **** indicate a significant decrease in foot edema in the positive control group or the millipede extract-administered group compared to the carrageenan-only group (con), * is p <0.05, ** is p <0.01, **** is p<0.0001.
본 발명은 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방 또는 개선용 건강기능식품 조성물에 관한 것이다.The present invention relates to a health functional food composition for preventing or improving arthritis and joint pain, containing an extract of millet sprouts as an active ingredient.
상기 관절염은 골관절염이고, 상기 관절통증은 골관절염에 의한 관절통증인 것이 바람직하지만, 이에 한정하지 않으며, 상기 유효성분은 MMP-1(Matrix metalloproteinase-1) 및 MMP-13의 발현을 저해시키고, GAG(Glycosaminoglycan)의 함량을 감소시키는 것이 특징이다.Preferably, the arthritis is osteoarthritis, and the joint pain is joint pain caused by osteoarthritis, but is not limited thereto, and the active ingredient inhibits the expression of MMP-1 (Matrix metalloproteinase-1) and MMP-13, and GAG (Glycosaminoglycan ) is characterized by reducing the content of
상기 조밥나물 추출물은 하기의 단계를 포함하는 방법에 의해 제조되는 것일 수 있으나, 이에 한정하지 않는다:The millet sprouts extract may be prepared by a method comprising the following steps, but is not limited thereto:
1) 조밥나물에 추출용매를 가하여 추출하는 단계;1) extracting by adding an extraction solvent to rice sprouts;
2) 단계 1)의 추출물을 여과하는 단계; 및2) filtering the extract of step 1); and
3) 단계 2)의 여과한 추출물을 감압 농축하고 건조하여 추출물을 제조하는 단계.3) preparing an extract by concentrating the filtered extract of step 2) under reduced pressure and drying it.
상기 단계 1)에서 추출용매는 물, C1~C4의 저급 알코올 또는 이들의 혼합물인 것이 바람직하며, 더 바람직하게는 에탄올 추출물, 더 더욱 바람직하게는 70%(v/v) 에탄올 추출물이지만 이에 한정하지 않는다. In step 1), the extraction solvent is preferably water, C 1 ~ C 4 lower alcohol or a mixture thereof, more preferably an ethanol extract, and even more preferably a 70% (v / v) ethanol extract. Not limited.
상기 제조방법에 있어서, 조밥나물의 추출은 여과법, 열수 추출, 침지 추출, 환류 냉각 추출 및 초음파 추출 등의 당 업계에 공지된 모든 통상적인 방법을 이용할 수 있다. 상기 단계 3)의 감압농축은 진공 감압 농축기 또는 진공회전증발기를 이용하는 것이 바람직하나 이에 한정하지 않는다. 또한, 건조는 감압건조, 진공건조, 비등건조, 분무 건조 또는 동결 건조하는 것이 바람직하나 이에 한정하지 않는다.In the above production method, all conventional methods known in the art, such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction, may be used for extraction of millet greens. The vacuum concentration in step 3) is preferably performed using a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, drying is preferably reduced pressure drying, vacuum drying, boiling drying, spray drying or freeze drying, but is not limited thereto.
상기 조성물은 분말, 과립, 환, 정제, 캡슐, 캔디, 시럽 및 음료 중에서 선택된 어느 하나의 제형으로 제조되는 것이 바람직하지만 이에 제한하는 것은 아니다.The composition is preferably prepared in any one formulation selected from powder, granule, pill, tablet, capsule, candy, syrup and beverage, but is not limited thereto.
본 발명의 건강기능식품 조성물을 식품첨가물로 사용하는 경우, 상기 조밥나물 추출물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 그의 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 조성물은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 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. 상기 식품의 종류에는 특별한 제한은 없다. 상기 추출물 또는 이의 분획물을 첨가할 수 있는 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 수프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합체 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다. When the health functional food composition of the present invention is used as a food additive, the millet greens 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 depending on the purpose of use (prevention, health or therapeutic treatment). In general, when preparing food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts 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 above the above range. There is no particular limitation on the type of food. Examples of foods to which the extract or its fraction can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea , drinks, alcoholic beverages, and vitamin complexes, and includes all health functional foods in the conventional sense.
본 발명의 조성물을 건강 음료로 사용할 경우, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 텍스트린, 사이클로텐스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 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 100g당 일반적으로 약 0.01~0.04g, 바람직하게는 약 0.02~0.03g이다. 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 중점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 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 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물은 100 중량부 당 0.01~0.1 중량부의 범위에서 선택되는 것이 일반적이다.When the composition of the present invention is used as a health drink, it may contain various flavoring agents or natural carbohydrates as additional components, like conventional drinks. The aforementioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclotenstrin, 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 to 0.04 g, preferably about 0.02 to 0.03 g per 100 g of the composition of the present invention. 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 agents, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonic acid It may contain a carbonation agent used in beverages and the like. 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 very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
또한, 본 발명은 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방 또는 치료용 약학 조성물에 관한 것이다.In addition, the present invention relates to a pharmaceutical composition for the prevention or treatment of arthritis and joint pain containing an extract of millet sprouts as an active ingredient.
상기 관절염은 골관절염이고, 상기 관절통증은 골관절염에 의한 관절통증인 것이 바람직하지만, 이에 한정하지 않는다.Preferably, the arthritis is osteoarthritis, and the joint pain is joint pain caused by osteoarthritis, but is not limited thereto.
본 발명의 조성물은 캡슐제, 산제, 과립제, 정제, 현탁액, 에멀젼, 시럽 및 에어로졸 중에서 선택된 어느 하나의 제형으로 제조되는 것이 바람직하지만 이에 한정하지 않는다.The composition of the present invention is preferably prepared in any one formulation selected from capsules, powders, granules, tablets, suspensions, emulsions, syrups and aerosols, but is not limited thereto.
본 발명의 조성물은 상기 유효성분 이외에 약학적으로 허용 가능한 담체, 부형제 또는 희석제를 더 포함할 수 있으며, 경구 또는 비경구의 여러 가지 제형일 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형 제제에는 캡슐제, 산제, 과립제, 정제, 환제 등이 포함되며, 이러한 고형 제제는 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. 경구 투여를 위한 액상 제제로는 현탁액, 에멀전, 시럽, 에어로졸 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성 용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성 용제 및 현탁 용제로는 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, 글리세로 젤라틴 등이 사용될 수 있다. 비경구 투여 시 피부 외용 또는 복강 내, 직장, 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관 내 주사 방식을 선택하는 것이 바람직하다.The composition of the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent in addition to the above active ingredient, and may be in various oral or parenteral formulations. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include capsules, powders, granules, tablets, pills, and the like, and these solid preparations include at least one excipient in one or more compounds, for example, starch, calcium carbonate, sucrose or lactose ( lactose) and gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, emulsions, syrups, aerosols, etc., and various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included in addition to water and liquid paraffin, which are commonly used simple diluents. 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 solvents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used. In the case of parenteral administration, it is preferable to select an external skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine intrathecal or intracerebrovascular injection method.
본 발명에 따른 약학 조성물은 약제학적으로 유효한 양으로 투여한다. 본 발명에 있어서, "약제학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효량의 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 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 level of the effective amount depends on the type, severity, and activity of the drug of the patient's disease. , sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field. The composition of 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 those skilled in the art.
본 발명의 조성물의 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설률 및 질환의 중증도에 따라 그 범위가 다양하며, 일일 투여량은 조밥나물 추출물의 양을 기준으로 0.01~2,000mg/kg이고, 바람직하게는 30~500mg/kg이고, 더욱 바람직하게는 50~300mg/kg이며, 하루 1~6회 투여될 수 있다. 본 발명의 조성물은 단독으로 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The dosage of the composition of the present invention varies in its range depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate and severity of the disease, and the daily dosage is the amount of millet sprouts extract 0.01 to 2,000 mg/kg as a standard, preferably 30 to 500 mg/kg, and more preferably 50 to 300 mg/kg, and may be administered 1 to 6 times a day. The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.
본 발명은 또한, 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방 또는 개선용 사료 첨가제에 관한 것이다.The present invention also relates to a feed additive for the prevention or improvement of arthritis and joint pain, containing a millet sprouts extract as an active ingredient.
본 발명의 사료 첨가제는 사료관리법상의 보조사료에 해당한다. 본 발명에서 용어 '사료'는 동물이 먹고, 섭취하며, 소화시키기 위한 또는 이에 적당한 임의의 천연 또는 인공 규정식, 한끼식 등 또는 상기 한끼식의 성분을 의미할 수 있다. 상기 사료의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용되는 사료를 사용할 수 있다. 상기 사료의 비제한적인 예로는, 곡물류, 근과류, 식품 가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류 또는 곡물 부산물류 등과 같은 식물성 사료; 단백질류, 무기물류, 유지류, 광물성류, 유지류, 단세포 단백질류, 동물성 플랑크톤류 또는 음식물 등과 같은 동물성 사료를 들 수 있다. 이들은 단독으로 사용되거나 2종 이상을 혼합하여 사용될 수 있다.The feed additive of the present invention corresponds to supplementary feed under the Feed Management Act. In the present invention, the term 'feed' may refer to any natural or artificial diet, one meal, etc., or a component of the one meal meal, suitable for or suitable for consumption by animals. The type of feed is not particularly limited, and feeds commonly used in the art may be used. Non-limiting examples of the feed include vegetable feeds such as grains, root fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal or grain by-products; Animal feed such as proteins, inorganic materials, oils, mineral oils, oils, single cell proteins, zooplankton, or food may be mentioned. These may be used alone or in combination of two or more.
본 발명은 또한, 조밥나물 추출물을 유효성분으로 함유하는 관절염 및 관절통증의 예방 또는 치료용 수의학적 조성물에 관한 것이다.The present invention also relates to a veterinary composition for the prevention or treatment of arthritis and joint pain, containing an extract of millet sprouts as an active ingredient.
본 발명의 조밥나물 추출물을 포함하는 수의학적 조성물은 통상의 방법에 따른 적절한 부형제 및 희석제를 더 포함할 수 있다. 본 발명의 조밥나물 추출물을 포함하는 수의학적 조성물에 포함될 수 있는 부형제 및 희석제로는, 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트, 세탄올, 스테아릴알콜, 유동파라핀, 솔비탄모노스테아레이트, 폴리소르베이트 60, 메칠파라벤, 프로필파라벤 및 광물유를 들 수 있다.The veterinary composition containing the crude herb extract of the present invention may further include appropriate excipients and diluents according to conventional methods. Examples of excipients and diluents that may be included in the veterinary composition containing the crude herb extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, and gelatin. , calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, cetanol, stearyl alcohol, liquid paraffin, sorbitan monostearate,
본 발명에 따른 조밥나물 추출물을 포함하는 수의학적 조성물은 충진제, 항응집제, 윤활제, 습윤제, 향신료, 유화제, 방부제 등을 추가로 포함할 수 있는데, 본 발명에 의한 수의학적 조성물은 동물에 투여된 후 활성 성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 당업계에 잘 알려진 방법을 사용하여 제형화될 수 있고, 제형은 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 용액, 시럽, 에어로졸, 연질 또는 경질 젤라틴 캅셀, 좌제, 멸균 주사용액, 멸균 외용제 등의 형태일 수 있다.The veterinary composition containing the millet sprouts extract according to the present invention may further include a filler, an anti-coagulant, a lubricant, a wetting agent, a spice, an emulsifier, a preservative, and the like. After the veterinary composition according to the present invention is administered to an animal, It can be formulated using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient, and the dosage form can be powders, granules, tablets, capsules, suspensions, emulsions, solutions, syrups, aerosols, It may be in the form of soft or hard gelatin capsules, suppositories, sterile solutions for injection, sterile external preparations, and the like.
본 발명에 의한 수의학적 조성물은 동물의 나이, 성별, 체중에 따라 달라질 수 있으나, 1일 1회 내지 수회 투여할 수 있고, 투여량은 투여경로, 질병의 정도, 성별, 체중, 나이 등에 따라서 증감될 수 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The veterinary composition according to the present invention may vary depending on the age, sex, and weight of the animal, but may be administered once or several times a day, and the dosage may increase or decrease depending on the route of administration, severity of disease, sex, weight, age, etc. It can be. Accordingly, the dosage is not intended to limit the scope of the present invention in any way.
이하, 실시예를 이용하여 본 발명을 더욱 상세하게 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로 본 발명의 범위가 이들에 의해 제한되지 않는다는 것은 당해 기술분야에서 통상의 지식을 가진 자에게 있어 자명한 것이다. Hereinafter, the present invention will be described in more detail using examples. These examples are only for explaining the present invention in more detail, and it is obvious to those skilled in the art that the scope of the present invention is not limited thereto.
실시예 1. 조밥나물 추출물의 제조Example 1. Manufacture of millet greens extract
본 발명의 1kg의 조밥나물에 대하여, 15ℓ의 70%(v/v) 에탄올을 가하고, 85℃에서 3시간 동안 추출한 후, 여과한 액을 45℃에서 감압 농축, 건조하여 조밥나물 추출물을 수득하였다.For 1 kg of the rice plant of the present invention, 15 liters of 70% (v / v) ethanol was added, extracted at 85 ° C. for 3 hours, and the filtered solution was concentrated under reduced pressure at 45 ° C. and dried to obtain a rice plant extract. .
실시예 2. 연골 세포에서 항염증 효능 평가 Example 2. Evaluation of anti-inflammatory efficacy in chondrocytes
인간 연골세포(SW1353)에서 조밥나물 추출물 처리에 따른 염증성 사이토카인 증가에 의해 활성화되는 연골기질 분해효소인 MMP-1(Matrix metalloproteinase-1) 및 MMP-13(Matrix metalloproteinase-13) 발현과 연골 프로테오글리칸(proteoglycan) 분해 산물인 GAG(Glycosaminoglycan) 함량의 변화를 확인하였다. Expression of matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13), which are cartilage matrix degrading enzymes activated by the increase in inflammatory cytokines following treatment with millet sprouts extract, in human chondrocytes (SW1353) and cartilage proteoglycan ( A change in the content of glycosaminoglycan (GAG), a proteoglycan degradation product, was confirmed.
[세포 배양][Cell culture]
DMEM/F12(Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12)에 10% FBS(Fetal Bovine Serum)가 첨가된 배양배지를 이용하여 인간 연골세포(SW1353)를 배양한 후, 조밥나물 추출물(25㎍/㎖)을 처리하고 2시간 동안 배양한 후, IL-1β(10ng/㎖)를 24시간 동안 처리하였다. After culturing human chondrocytes (SW1353) using a culture medium in which 10% FBS (Fetal Bovine Serum) was added to DMEM/F12 (Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12), millet sprouts extract (25 μg/day) ㎖) and cultured for 2 hours, and then treated with IL-1β (10 ng/㎖) for 24 hours.
(1) IL-1β가 매개하는 MMP-1 및 MMP-13의 발현 감소 효과 확인(1) Confirmation of IL-1β-mediated expression reduction effect of MMP-1 and MMP-13
염증성 사이토카인의 분비에 따른 MMPs의 활성화 및 합성으로 연골조직을 구성하는 연골기질분자(extracellular matrix, ECM)가 분해되는데, 조밥나물 추출물이 MMPs의 생성에 영향을 주는지 ELISA 키트(R & D Systems)를 이용하여 확인하였다. The activation and synthesis of MMPs following the secretion of inflammatory cytokines degrades the extracellular matrix (ECM) that composes cartilage tissue. It was confirmed using .
그 결과, IL-1β를 24시간 처리한 배양 상등액에서 MMP-1 및 MMP-13의 발현량이 증가하였으나, 본 발명의 조밥나물 추출물이 전처리된 세포에서는 IL-1β에 의한 MMP-1 및 MMP-13의 발현량이 유의미하게 감소하였다(도 1).As a result, the expression levels of MMP-1 and MMP-13 were increased in the culture supernatant treated with IL-1β for 24 hours. The expression level of was significantly decreased (FIG. 1).
(2) IL-1β에 의해 유도된 GAG(Glycosaminoglycan) 분비 효과 확인(2) Confirmation of GAG (Glycosaminoglycan) secretion effect induced by IL-1β
GAG는 연골조직을 구성하는 성분으로 프로테오글리칸(proteoglycan)이 분해되어 생성되는 물질이며, 본 발명의 조밥나물 추출물이 프로테오글리칸의 분해에 영향을 주는지 확인하기 위하여 GAG의 함량 변화를 확인하였다. 구체적으로, IL-1β를 24시간 처리한 후 배양 상등액을 blyscan dye와 반응시켜 656nm에서 흡광도를 측정하여 GAG 양을 측정하였다. GAG is a component constituting cartilage tissue and is a material produced by decomposition of proteoglycan, and changes in the content of GAG were confirmed in order to determine whether the crude herb extract of the present invention affects the degradation of proteoglycan. Specifically, after treatment with IL-1β for 24 hours, the culture supernatant was reacted with blyscan dye to measure absorbance at 656 nm to measure the amount of GAG.
그 결과, IL-1β로 인해 연골 분해가 촉진되어 증가된 GAG 양이 본 발명의 조밥나물 추출물 처리에 의해 감소하는 것을 확인하였다(도 2). As a result, it was confirmed that cartilage decomposition was promoted by IL-1β, and the increased amount of GAG was reduced by treatment with the millet sprouts extract of the present invention (FIG. 2).
실시예 3. 아세트산 유도에 의한 통증 유발 동물모델에서 진통 효능 평가Example 3. Evaluation of analgesic efficacy in pain-induced animal models by acetic acid induction
7주령 ICR 마우스를 일주일 동안 순화시킨 후, 조밥나물 추출물(150mg/kg, 300mg/kg) 및 양성대조군인 디클로페낙(diclofenac, 10mg/kg)을 각각 경구 투여하였다. 투여하고 1시간 후에 마우스 복강에 0.75%(v/v) 아세트산(초산), 10㎖/kg의 용량으로 복강투여 하였고, 아세트산 복강투여를 위해 18시간 이상 절식시켰다. 아세트산 투여하고 5분 후, 10분 동안 마우스가 몸을 비트는 횟수를 관찰하였다. After 7-week-old ICR mice were acclimatized for one week, crude herb extract (150mg/kg, 300mg/kg) and positive control diclofenac (10mg/kg) were orally administered, respectively. 1 hour after administration, 0.75% (v/v) acetic acid (acetic acid) was intraperitoneally administered to the mouse at a dose of 10 ml/kg, and fasted for at least 18 hours for intraperitoneal administration of acetic acid. Five minutes after administration of acetic acid, the number of times the mouse twisted its body was observed for 10 minutes.
그 결과, 아세트산의 복강 내 투여로 인해 모세혈관의 손상과 통증이 유발하여 마우스의 몸을 비트는 횟수가 증가하였으나, 조밥나물 추출물을 투여한 경우, 마우스가 몸을 비트는 횟수가 유의미하게 감소하였다(도 3).As a result, intraperitoneal administration of acetic acid caused capillary damage and pain, resulting in an increase in the number of twists in the mouse, but when the extract was administered, the number of twists in the mouse was significantly reduced. (Fig. 3).
실시예 4. 카라기난에 의한 염증 유발 동물모델에서 족부 부종 완화 효능평가Example 4. Efficacy evaluation of relieving foot edema in an animal model inducing inflammation by carrageenan
7주령 ICR 마우스를 일주일 동안 순화시킨 후, 조밥나물 추출물(150mg/kg, 300mg/kg) 및 양성대조군인 인도메타신(indomethacin, 5mg/kg)을 경구 투여하였다. 투여하고 1시간 후에, 1% 카라기난(Carrageenan) 50㎕를 오른쪽 뒷다리 발바닥에 투여한 후 1, 3, 5시간 간격으로 오른쪽 뒷다리 족부의 부종 크기를 부종 측정기(Plethysmometer, Bioseb, USA)를 이용해 비교하였다. After 7-week-old ICR mice were acclimatized for one week, they were orally administered with crude herb extract (150 mg/kg, 300 mg/kg) and indomethacin (5 mg/kg) as a positive control group. 1 hour after administration, 50 μl of 1% carrageenan was administered to the sole of the right hind limb, and then the size of the edema of the right hind limb was compared at 1, 3, and 5 hour intervals using a edema meter (Plethysmometer, Bioseb, USA). .
그 결과, 카라기난으로 유도한 족부 부종 동물모델에서 조밥나물 추출물 투여로 인해 부종 유발 5시간째에 족부 부종이 유의적으로 감소한 것을 확인하였다(도 4).As a result, in the carrageenan-induced foot edema animal model, it was confirmed that foot edema was significantly reduced at 5 hours after edema induction due to the administration of millet sprouts extract (FIG. 4).
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