KR101806474B1 - A composition for improving, preventing and treating of bone diseases comprising Tenebrio molitor extract - Google Patents
A composition for improving, preventing and treating of bone diseases comprising Tenebrio molitor extract Download PDFInfo
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- KR101806474B1 KR101806474B1 KR1020160139137A KR20160139137A KR101806474B1 KR 101806474 B1 KR101806474 B1 KR 101806474B1 KR 1020160139137 A KR1020160139137 A KR 1020160139137A KR 20160139137 A KR20160139137 A KR 20160139137A KR 101806474 B1 KR101806474 B1 KR 101806474B1
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/63—Arthropods
- A61K35/64—Insects, e.g. bees, wasps or fleas
-
- 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
-
- 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
-
- 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
-
- 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
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/204—Animal extracts
Abstract
Description
본 발명은 갈색거저리(Tenebrio molitor) 추출물을 유효성분으로 함유하는 골질환의 개선, 예방 또는 치료용 조성물에 관한 것이다.The invention mealworm (Tenebrio The present invention relates to a composition for improving, preventing or treating bone diseases containing, as an active ingredient,
골 조직은 연골과 골격계를 구성하며 기계적 기능으로 지지와 근 부착의 역할을 하고, 생체기관 및 골수를 보호하는 기능을 하며, 칼슘과 인 이온의 항상성 유지를 위해 이들을 보존하는 기능을 담당한다. 이와 같은 기능을 하는 골 조직은 교원질, 당단백질과 같은 세포 기질과 조골세포, 파골세포 및 골세포 등 여러 종류의 세포들로 이루어진다. Bone tissue constitutes the cartilage and skeletal system. It plays a role of support and muscle attachment by mechanical function, protects organism and bone marrow, and preserve calcium and phosphorus to maintain homeostasis. Bone tissue that functions like this is composed of many kinds of cells such as collagen, glycoprotein, and osteoblast, osteoclast, and osteocyte.
이들 중 파골세포는 조혈모세포로부터 유래한 세포로서 노화된 골의 흡수를 담당하며, 조골세포는 골수 내 간질세포(bone marrow stromal cell)로부터 유래한 세포로서 골 형성에 주된 역할을 담당한다.Among them, osteoclasts are cells derived from hematopoietic stem cells, which are responsible for the absorption of aged bone. Osteoblasts are derived from bone marrow stromal cells and play a major role in osteogenesis.
상기 파골세포는 마우스의 RAW264.7 단핵구 세포가 RANKL(receptor activator of nuclear factor κB (RANK)ligand)에 의해 다핵 파골세포(multinucleated osteoclasts)로 분화된다. 이러한 분화 과정은 세포 외부의 RANKL이 RANK에 결합하여 미토겐 활성 단백질 키나아제(mitogen-activated protein kinase, MAPK)의 활성을 촉진하고, 이는 NF-κB라는 전사 인자가 핵 내로 들어가서 파골세포 분화와 관련된 TRAP(tartrate-resistant acid phosphatase), MMP-9(matrix metalloproteinase-9), c-Src 티로신 키나아제(tyrosine kinase) 등의 발현을 증가시킴으로써 가능한데, 이러한 과정으로 형성된 다핵 파골세포는 무기질 골(mineralized bone)을 흡수하는 역할을 한다. 또한, RANKL이 RANK에 결합하면 TRAF6(tumor necrosis factor receptor-associated factor 6)의 활성을 촉진시켜 MAPK, 또는 NF-κB, AP-1, NFATc1과 같은 전사인자들의 활성을 촉진시킨다(Lee ZH, Kim HH. Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts. Biochem Biophys Res Commun. 2003 May 30, 305, 211-4). 따라서 RANKL에 의해 활성화되는 신호전달 경로의 차단은 골다공증을 비롯한 골 질환의 치료를 위한 치료적 접근 방법 중의 하나로 인지되고 있다.The osteoclast is differentiated into multinucleated osteoclasts by RANKL (RANKL) ligand of RAW264.7 mononuclear cells in mouse. This differentiation process promotes the activation of mitogen-activated protein kinase (MAPK) by RANKL binding to RANK in the extracellular region, and this is because the transcription factor NF-κB enters into the nucleus and binds to osteoclast differentiation-related TRAP (MMP-9) and tyrosine kinase (tyrosine kinase). These multinuclear osteoclasts formed a mineralized bone, It plays a role of absorption. In addition, when RANKL binds to RANK, the activity of TRAF6 (tumor necrosis factor receptor-associated factor 6) is promoted to promote the activation of transcription factors such as MAPK or NF-κB, AP-1 and NFATc1 HH. Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts. Biochem Biophys Res Commun 2003 May 30, 305, 211-4). Therefore, blocking of the signaling pathway activated by RANKL is recognized as one of the therapeutic approaches for the treatment of osteoporosis and other bone diseases.
이처럼 골형성은 파골세포(osteoclast)에 의한 골 흡수(bone resoprtion)와 조골세포(osteoblast)에 의한 골형성(bone formation)의 대등한 작용에 의한 리모델링 과정(bone remodeling)이 지속적으로 조절됨으로써 유지된다. 그러나, 파골세포의 과도한 활성이나 조골세포의 활성 저하는 골형성의 리모델링 과정에서 불균형을 초래하여, 생체 내에서 파골세포와 조골세포와의 평형이 깨짐으로써 골질환을 유발하게 된다.Thus, bone formation is maintained by continuously controlling bone remodeling by the equivalent action of bone resorption by osteoclast and osteoblast formation (bone formation) . However, the excessive activity of osteoclasts and the depletion of osteoblasts leads to an imbalance in the remodeling process of osteogenesis, resulting in the destruction of equilibrium between osteoclasts and osteoblasts.
골 질환의 대표적인 예로서 골다공증은 골형성과 골흡수의 평형이 깨져 골흡수가 우월하게 일어남으로써 뼈의 밀도가 약화되어 일어나는 질환으로, 현재 미국에서만 약 천만명이 이미 골다공증에 걸려있으며 1천 8백만명이 낮은 골밀도를 갖고 있어서 골다공증의 위험에 놓여 있다. 또한, 일생 동안 여성 2명중 1명, 남성의 경우 8명중 1명이 골다공증과 관련된 골절을 경험하며, 이미 2백만명 이상의 미국 남성들이 골다공증 질환을 앓고 있다. 미국에서는 골다공증과 관련된 질병과 골절로 인한 직접적인 지출이 매년 140억 달러에 달하고 있다. 국내에서의 경우에도 약 400 백만명이 골다공증에 걸려있거나 그 위험에 있으며, 이는 노령화 사회로 접어들면서 더 증가할 것으로 추정되어, 이로 인한 사회적 지출과 가족구성원의 정신적, 경제적 지출이 클 것으로 예상된다.As a typical example of osteoporosis, osteoporosis is a disease caused by weakening bone density due to breakage of equilibrium of osteogenesis and bone resorption and superior bone resorption. Currently, about 10 million people are already suffering from osteoporosis in the United States and 18 million people It has low bone density and is at risk of osteoporosis. In addition, one in two women and one in eight men experience lifelong fractures associated with osteoporosis, and over two million Americans already have osteoporosis. In the United States, direct spending on osteoporosis-related illnesses and fractures amounts to $ 14 billion annually. In Korea, about 400 million people are at risk for osteoporosis, and it is estimated that they will increase more as they move into an aging society. It is expected that social spending and psychological and economic expenditure of family members will be large.
따라서, 환자에게 독성이 없으면서 파골세포의 골 흡수를 억제하는 새로운 물질이 요구되고 있다.Therefore, there is a need for a novel substance that inhibits bone resorption of osteoclasts without toxicity to the patient.
본 발명의 목적은 갈색거저리(Tenebrio molitor) 추출물을 유효성분으로 함유하는 골질환의 예방 또는 치료용 약학 조성물을 제공하는데 있다.The object of the present invention is to provide a method for the treatment of brown duck ( Tenebrio The present invention also provides a pharmaceutical composition for preventing or treating osteoporosis.
또한, 본 발명의 다른 목적은 갈색거저리(Tenebrio molitor) 추출물을 유효성분으로 함유하는 골질환의 개선 또는 예방용 식품 조성물을 제공하는데 있다.In addition, another object of the present invention is to provide a method and apparatus for detecting the presence of brown gill ( Tenebrio The present invention also provides a food composition for improving or preventing osteoporosis.
상기한 목적을 달성하기 위한 본 발명의 골질환의 예방 또는 치료용 약학 조성물은 갈색거저리(Tenebrio molitor) 추출물을 유효성분으로 함유할 수 있다.A pharmaceutical composition for the treatment or prevention of bone diseases of the present invention for achieving the above object mealworm (Tenebrio molitor ) extract as an active ingredient.
상기 갈색거저리 추출물은 갈색거저리와 물, 탄소수 1 내지 4의 저급알코올 또는 이들의 혼합용매를 1 : 0.3 내지 10의 부피비로 혼합하여 추출하는 것일 수 있다.The brown gruel extract may be obtained by mixing brown gruel and water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof in a volume ratio of 1: 0.3 to 10.
상기 혼합용매는 20 내지 80 부피%의 메탄올, 에탄올, 부탄올 또는 프로판올 수용액일 수 있다.The mixed solvent may be 20 to 80% by volume of an aqueous solution of methanol, ethanol, butanol or propanol.
상기 갈색거저리 추출물은 90 내지 120 ℃의 온도 및 0.2 내지 0.8 kgforce/㎤의 압력 하에서 수득되는 것일 수 있다.The brown gruel extract may be obtained at a temperature of 90 to 120 DEG C and a pressure of 0.2 to 0.8 kg force / cm3.
상기 골질환은 골다공증, 골연화증, 구루병, 무형성 골질환 또는 암세포의 골전이에 의해 초래되는 뼈의 손상인 것일 수 있다.The bone disease may be bone damage caused by osteoporosis, osteomalacia, rickets, intractable bone disease or bone cancer of cancer cells.
또한, 상기한 다른 목적을 달성하기 위한 본 발명의 골질환의 개선 또는 예방용 식품 조성물은 갈색거저리(Tenebrio molitor) 추출물을 유효성분으로 함유할 수 있다.Moreover, improvement or food composition for the prevention of bone disease of the present invention to achieve another object above is mealworm (Tenebrio molitor ) extract as an active ingredient.
본 발명의 골질환의 개선, 예방 또는 치료용 조성물은 파골세포의 형성을 감소시켜 골 흡수를 억제하며 이를 통하여 다양한 골질환의 개선, 예방 또는 치료에 매우 효과적으로 작용하며, 더욱이 독성이 없으므로 식품의 형태로도 섭취할 수 있다. The composition for improving, preventing or treating osteopathy of the present invention reduces the formation of osteoclast to inhibit bone resorption and thus effectively works for the improvement, prevention or treatment of various bone diseases. Furthermore, since it is not toxic, .
또한, 본 발명은 골다공증 및 암 세포의 골전이로 인하여 발생된 골질환에 대하여 예방 및 치료 효능을 가지는 의약 및 식품으로서의 기초적인 자료를 제공한다.In addition, the present invention provides basic data as medicines and foods having preventive and therapeutic efficacy against osteoporosis and osteopathy caused by osteoporosis of cancer cells.
도 1A는 마우스에 식이를 28일 동안 섭취시켜 변화된 체중을 나타낸 그래프이며, 도 1B는 8주 동안 마우스가 섭취한 식이의 양을 나타낸 그래프이고, 도 1C는 8주 동안 마우스의 혈당 수준을 나타낸 그래프이다.
도 2A는 Non-OVX_DW(NON/DW) 마우스 군의 골단(epiphysis)을 헤마톡실린&에오신으로 염색한 사진이며, 도 2B는 Non-OVX_TM(NON/TW) 마우스 군의 골단(epiphysis)을 헤마톡실린&에오신으로 염색한 사진이고, 도 2C는 OVX_DW 마우스 군의 골단(epiphysis)을 헤마톡실린&에오신으로 염색한 사진이며, 도 2D는 OVX_TM 마우스 군의 골단(epiphysis)을 헤마톡실린&에오신으로 염색한 사진이고, 도 2E는 각 마우스군 넓적다리뼈의 골피질(cortical bone) 두께를 나타낸 그래프이며, 도 2F는 각 마우스군 넓적다리뼈의 뼈기둥(trabecular bone)의 부피를 나타낸 그래프이다.FIG. 1B is a graph showing the amount of diet consumed by the mouse for 8 weeks, FIG. 1C is a graph showing the blood glucose level of the mouse for 8 weeks, and FIG. to be.
FIG. 2A is a photograph of the epiphysis of Non-OVX_DW (NON / DW) mouse group stained with hematoxylin and eosin, and FIG. 2B is a photograph showing the epiphysis of Non-OVX_TM FIG. 2C is a photograph of the epiphysis of OVX_DW mouse group stained with hematoxylin and eosin, FIG. 2D shows the epiphysis of OVX_TM mouse group with hematoxylin and eosin FIG. 2E is a graph showing the thickness of the cortical bone of the thighbone of each mouse group, and FIG. 2F is a graph showing the volume of the trabecular bone of each mouse group of the thighbone .
본 발명은 갈색거저리(Tenebrio molitor) 추출물을 유효성분으로 함유하는 골질환의 개선, 예방 또는 치료용 조성물에 관한 것이다.
The invention mealworm (Tenebrio The present invention relates to a composition for improving, preventing or treating bone diseases containing, as an active ingredient,
이하, 본 발명을 상세하게 설명한다. Hereinafter, the present invention will be described in detail.
본 발명의 골질환의 개선, 예방 또는 치료용 조성물은 갈색거저리(Tenebrio molitor) 추출물을 유효성분으로 함유한다.The composition for improving, preventing or treating bone diseases of the present invention contains an extract of Tenebrio molitor as an active ingredient.
상기 갈색거저리(Tenebrio molitor)는 많은 나라에서 음식 소스로 이용되는 곤충 중 하나이며, 골질환을 개선, 예방 또는 치료할 수 있는 효과에 대하여 알려져 있지 않다. The brown goat ( Tenebrio molitor ) is one of the insects used as a food source in many countries and is not known for its effect of improving, preventing or treating bone diseases.
상기 갈색거저리 추출물을 제조하기 위하여, 먼저 갈색거저리를 물에 세척하고 건조한다.To prepare the brown gruel extract, the brown gruel is first washed in water and dried.
다음으로, 상기 세척된 갈색거저리와 추출용매를 1 : 0.3 내지 10의 부피비, 바람직하게는 1 : 0.5 내지 5의 부피비로 혼합하여 90 내지 120 ℃, 바람직하게는 100 내지 110 ℃의 온도 및 0.2 내지 0.8 kgforce/㎤, 바람직하게는 0.4 내지 0.5 kgforce/㎤의 압력 하에서 10분 내지 10시간, 바람직하게는 15분 내지 3시간 동안 추출하여 추출물을 제조한다.Next, the washed brown gill and the extraction solvent are mixed at a volume ratio of 1: 0.3 to 10, preferably 1: 0.5 to 5, at a temperature of 90 to 120 DEG C, preferably 100 to 110 DEG C, The extract is prepared by extracting under a pressure of 0.8 kg force /
상기 추출온도, 압력 및 시간이 상기 하한치 미만인 경우에는 원하는 효과를 유도할 수 없으며, 상기 상한치 초과인 경우에는 독성물질이 발생할 수 있다.If the extraction temperature, pressure, and time are less than the lower limit, a desired effect can not be obtained. If the extraction temperature, pressure, and time are above the upper limit, toxic substances may be generated.
상기 추출용매는 물, 탄소수 1 내지 4의 저급알코올 또는 이들의 혼합용매이며, 바람직하게는 물이다. 상기 혼합용매로는 특별히 한정하는 것은 아니지만 20 내지 80%의 메탄올, 에탄올, 부탄올 또는 프로판올을 들 수 있다. The extraction solvent is water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof, preferably water. The mixed solvent is not particularly limited, but methanol, ethanol, butanol or propanol of 20 to 80% is exemplified.
상기 추출시 갈색거저리와 추출용매의 중량비가 벗어나는 경우에는 추출물에 갈색거저리의 유효성분이 적은 양으로 추출될 수 있다. When the weight ratio of the brown gruel to the extraction solvent is out of the above range, the effective amount of the brown gruel can be extracted in a small amount to the extract.
본 명세서에서 갈색거저리를 언급하면서 사용되는 용어 '추출물'은 추출용매를 처리하여 얻은 조추출물뿐만 아니라 갈색거저리 추출물의 가공물도 포함한다. 예를 들어, 갈색거저리의 추출물은 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.The term " extract " used herein in reference to a brown gruel includes not only crude extracts obtained by treating extraction solvents, but also those of brown gruel extracts. For example, the extract of brown goat can be prepared in powder form by an additional process such as vacuum distillation and freeze drying or spray drying.
또한, 본 발명의 갈색거저리 추출물은 광의로는 갈색거저리를 동물에게 투여할 수 있도록 제형화된 갈색거저리의 가공물, 예컨대, 갈색거저리 분말도 포함하는 의미를 갖는다. 비록 본 발명에서 갈색거저리 추출물로 실험을 진행하긴 하였으나, 갈색거저리의 가공물과 같은 형태로도 목적하는 효과를 달성할 수 있음은 당업자라면 예상 가능할 것이다.In addition, the brown gruel extract of the present invention has a meaning including a brown gruel product, such as brown gruel powder, formulated so as to be able to administer to the animal a brown gruel in a broad sense. Although the present invention has been carried out with brown goat extracts, it will be appreciated by those skilled in the art that the desired effects can be achieved in the same manner as brown goat's products.
한편, 본 명세서에서 용어 '유효성분으로 함유하는'이란 갈색거저리 추출물의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 일예로, 상기 갈색거저리 추출물은 10 내지 1500 ㎍/㎖, 바람직하게는 100 내지 1000 ㎍/㎖의 농도로 사용된다. 갈색거저리 추출물은 천연물로서 과량 투여하여도 인체에 부작용이 없으므로 본 발명의 조성물 내에 포함되는 갈색거저리 추출물의 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.
The term " comprising as an active ingredient ", as used herein, is meant to include an amount sufficient to achieve the efficacy or activity of a ganoderma lucidum extract. For example, the brown gruel extract is used at a concentration of 10 to 1500 μg / ml, preferably 100 to 1000 μg / ml. The brown gourd extract is a natural product and there is no adverse effect on the human body even when it is administered in an excessive amount. Therefore, the quantitative upper limit of the brown gourd extract contained in the composition of the present invention can be selected by a person skilled in the art within a suitable range.
본 발명의 약제학적 조성물은 상기 유효 성분 이외에 약제학적으로 적합하고 생리학적으로 허용되는 보조제를 사용하여 제조될 수 있으며, 상기 보조제로는 부형제, 붕해제, 감미제, 결합제, 피복제, 팽창제, 윤활제, 활택제 또는 향미제 등을 사용할 수 있다.The pharmaceutical composition of the present invention can be prepared by using pharmaceutically acceptable and physiologically acceptable adjuvants in addition to the above-mentioned active ingredients. Examples of the adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, A lubricant or a flavoring agent can be used.
상기 약제학적 조성물은 투여를 위해서 상기 기재한 유효 성분 이외에 추가로 약제학적으로 허용 가능한 담체를 1종 이상 포함하여 약제학적 조성물로 바람직하게 제제화할 수 있다.The pharmaceutical composition may be formulated into a pharmaceutical composition containing at least one pharmaceutically acceptable carrier in addition to the above-described active ingredients for administration.
상기 약제학적 조성물의 제제 형태는 과립제, 산제, 정제, 피복정, 캡슐제, 좌제, 액제, 시럽, 즙, 현탁제, 유제, 점적제 또는 주사 가능한 액제 등이 될 수 있다. 예를 들어, 정제 또는 캡슐제의 형태로의 제제화를 위해, 유효 성분은 에탄올, 글리세롤, 물 등과 같은 경구, 무독성의 약제학적으로 허용 가능한 불활성 담체와 결합될 수 있다. 또한, 원하거나 필요한 경우, 적합한 결합제, 윤활제, 붕해제 및 발색제 또한 혼합물로 포함될 수 있다. 적합한 결합제는 이에 제한되는 것은 아니나, 녹말, 젤라틴, 글루코스 또는 베타-락토오스와 같은 천연 당, 옥수수 감미제, 아카시아, 트래커캔스 또는 소듐올레이트와 같은 천연 및 합성 검, 소듐 스테아레이트, 마그네슘 스테아레이트, 소듐 벤조에이트, 소듐 아세테이트, 소듐 클로라이드 등을 포함한다. 붕해제는 이에 제한되는 것은 아니나, 녹말, 메틸 셀룰로스, 아가, 벤토니트, 잔탄 검 등을 포함한다.The pharmaceutical composition may be in the form of granules, powders, tablets, coated tablets, capsules, suppositories, liquids, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation into tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Also, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included as a mixture. Suitable binders include, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, natural and synthetic gums such as corn sweeteners, acacia, tracker candles or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum and the like.
액상 용액으로 제제화되는 조성물에 있어서 허용 가능한 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.Acceptable pharmaceutical carriers for compositions that are formulated into a liquid solution include sterile water and sterile water suitable for the living body such as saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.
더 나아가 해당분야의 적절한 방법으로 Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.
본 발명의 약제학적 조성물은 경구 또는 비경구로 투여할 수 있고, 비경구 투여인 경우에는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있으며, 바람직하게는 경구 투여이다.The pharmaceutical composition of the present invention can be administered orally or parenterally. In the case of parenteral administration, the composition can be administered by intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection, transdermal administration, etc., .
본 발명의 약제학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사는 소망하는 치료 또는 예방에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다. 본 발명의 바람직한 구현예에 따르면, 본 발명의 약제학적 조성물의 1일 투여량은 0.001-10 g/kg이다.The appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate and responsiveness of the patient, Usually, a skilled physician can readily determine and prescribe dosages effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.001-10 g / kg.
본 발명의 약제학적 조성물은 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액 또는 유화액 형태이거나 엑스제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention can be prepared in unit dose form by formulating it with a pharmaceutically acceptable carrier and / or excipient or can be manufactured by inserting it into a multi-dose container. The formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
또한, 본 발명은 갈색거저리 추출물을 유효성분으로 함유하는 골질환의 개선 또는 예방용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for improving or preventing bone diseases, which comprises an extract of brown gruel as an active ingredient.
본 발명에 따른 식품 조성물은 상기 약제학적 조성물과 동일한 방식으로 제제화되어 기능성 식품으로 이용하거나, 각종 식품에 첨가할 수 있다. 본 발명의 조성물을 첨가할 수 있는 식품으로는 예를 들어, 음료류, 알코올 음료류, 과자류, 다이어트바, 유제품, 육류, 초코렛, 피자, 라면, 기타 면류, 껌류, 아이스크림류, 비타민 복합제, 건강보조식품류 등이 있다.The food composition according to the present invention can be formulated in the same manner as the above pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, confectioneries, diet bars, dairy products, meat, chocolates, pizza, ram noodles, other noodles, gums, ice cream, .
본 발명의 식품 조성물은 유효성분으로서 갈색거저리 추출물뿐만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제와 음료류로 제조되는 경우에는 본 발명의 갈색거저리 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 및 각종 식물 추출액 등을 추가로 포함시킬 수 있다.The food composition of the present invention may contain, as an active ingredient, a brown gruel extract as well as a component that is ordinarily added at the time of food production, and includes, for example, proteins, carbohydrates, fats, nutrients, flavoring agents, and flavoring agents . Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavorings such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavorings (saccharine, aspartame, etc.) can be used as flavorings. For example, when the food composition of the present invention is prepared from a drink and a beverage, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, various plant extracts and the like may be further added in addition to the brown gruel extract of the present invention .
본 발명은 상기 갈색거저리 추출물을 유효성분으로 포함하는 골질환의 개선 또는 예방용 식품 조성물을 포함하는 건강기능식품을 제공한다. 건강기능식품이란, 갈색거저리 추출물을 음료, 차류, 향신료, 껌, 과자류 등의 식품소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용시 발생할 수 있는 부작용 등이 없는 장점이 있다. 이와 같이 하여 얻어지는 본 발명의 건강기능식품은, 일상적으로 섭취하는 것이 가능하기 때문에 매우 유용하다. 이와 같은 건강기능식품에 있어서의 갈색거저리 추출물의 첨가량은, 대상인 건강기능식품의 종류에 따라 달라 일률적으로 규정할 수 없지만, 식품 본래의 맛을 손상시키지 않는 범위에서 첨가하면 되며, 대상 식품에 대하여 통상 0.01 내지 50 중량%, 바람직하기로는 0.1 내지 20 중량%의 범위이다. 또한, 환제, 과립제, 정제 또는 캡슐제 형태의 건강기능식품의 경우에는 통상 0.1 내지 100 중량% 바람직하기로는 0.5 내지 80 중량%의 범위에서 첨가하면 된다. 한 구체예에서, 본 발명의 건강기능식품은 환제, 정제, 캡슐제 또는 음료의 형태일 수 있다.The present invention provides a health functional food comprising a food composition for improving or preventing osteopathy which comprises the brown gurrhoid extract as an active ingredient. A health functional food is a food made by adding a brown goat extract to a food material such as beverage, tea, spice, gum, or confection, or encapsulated, powdered or suspended, and has a health-specific effect However, unlike general medicine, there is an advantage that there is no side effect that can occur when a food is used as a raw material and a drug is taken for a long time. The health functional food of the present invention thus obtained is very useful because it can be ingested routinely. The amount of the brown gourd extract added in such a health functional food can not be uniformly determined depending on the kind of the health functional food to which it is added but may be added within a range that does not impair the original taste of the food, 0.01 to 50% by weight, preferably 0.1 to 20% by weight. In the case of health functional foods in the form of pills, granules, tablets or capsules, they may be added usually in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a pill, tablet, capsule or beverage.
또한, 본 발명은 골질환의 개선, 예방 또는 치료용 의약 또는 식품의 제조를 위한 갈색거저리 추출물의 용도를 제공한다. 상기한 바와 같이 갈색거저리 추출물은 골질환의 개선, 예방 또는 치료를 위한 용도로 이용될 수 있다.In addition, the present invention provides the use of a ganoderma extract for the manufacture of a medicament or food for improving, preventing or treating bone diseases. As described above, the brown gruel extract can be used for the purpose of improving, preventing or treating bone diseases.
또한, 본 발명은 포유동물에게 유효량의 갈색거저리 추출물을 투여하는 것을 포함하는 골질환의 개선, 예방 또는 치료용 방법을 제공한다.The present invention also provides a method for the improvement, prevention or treatment of bone disease comprising administering to a mammal an effective amount of a brown gruel extract.
여기에서 사용된 용어 "포유동물"은 치료, 관찰 또는 실험의 대상인 포유동물을 말하며, 바람직하게는 인간을 말한다.The term "mammal " as used herein refers to a mammal that is the subject of treatment, observation or experimentation, preferably a human.
여기에서 사용된 용어 "유효량"은 연구자, 수의사, 의사 또는 기타 임상의에 의해 생각되는 조직계, 동물 또는 인간에서 생물학적 또는 의학적 반응을 유도하는 유효 성분 또는 약학적 조성물의 양을 의미하는 것으로, 이는 해당 질환 또는 장애의 증상의 완화를 유도하는 양을 포함한다. 본 발명의 유효 성분에 대한 유효량 및 투여횟수는 원하는 효과에 따라 변화될 수 있다. 그러므로, 투여될 최적의 투여량은 당업자에 의해 쉽게 결정될 수 있으며, 질환의 종류, 질환의 중증도, 조성물에 함유된 유효성분 및 다른 성분의 함량, 제형의 종류, 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다. 본 발명의 예방, 치료 또는 개선 방법에 있어서, 성인의 경우, 갈색거저리 추출물을 1일 1회 내지 수회 투여시, 0.001 g/kg 내지 10 g/kg의 용량으로 투여하는 것이 바람직하다.As used herein, the term "effective amount" refers to the amount of active ingredient or pharmaceutical composition that elicits a biological or medical response in a tissue system, animal, or human, as contemplated by a researcher, veterinarian, physician or other clinician, ≪ / RTI > inducing a reduction of the symptoms of the disease or disorder. The effective amount and the administration frequency for the active ingredient of the present invention can be changed according to the desired effect. Thus, the optimal dosage to be administered can be readily determined by those skilled in the art and will vary with the nature of the disease, the severity of the disease, the amount of active and other ingredients contained in the composition, the type of formulation, and the age, The age, body weight, sex, diet, time of administration, route of administration and fraction of the composition, duration of treatment, concurrent medication, and the like. In the prevention, treatment or improvement of the present invention, it is preferable to administer the brown gruel extract at a dose of 0.001 g / kg to 10 g / kg once or several times a day for an adult.
본 발명의 치료방법에서 갈색거저리 추출물을 유효 성분으로 포함하는 조성물은 경구, 직장, 정맥내, 동맥내, 복강내, 근육내, 흉골내, 경피, 국소, 안구내 또는 피내 경로를 통해 통상적인 방식으로 투여할 수 있다.
In the method of treatment according to the present invention, the composition comprising the brown gruel extract as an active ingredient can be administered orally, rectally, intravenously, intraarterally, intraperitoneally, intramuscularly, intrasternally, transdermally, topically, ≪ / RTI >
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시하나, 하기 실시예는 본 발명을 예시하는 것일 뿐 본 발명의 범주 및 기술사상 범위 내에서 다양한 변경 및 수정이 가능함은 당업자에게 있어서 명백한 것이며, 이러한 변형 및 수정이 첨부된 특허청구범위에 속하는 것도 당연한 것이다.It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the present invention. Such variations and modifications are intended to be within the scope of the appended claims.
실시예 1. 갈색거저리 물 추출물 Example 1. Brown gruel water extract
100 mL의 증류수와 2배 부피의 갈색거저리(Tenebrio molitor)를 혼합하여 110 ℃의 온도 및 0.4 kgforce/㎤의 압력 하에서 15분 동안 열수추출한 후 반응이 완료되면 원심분리기를 이용하여 4 ℃에서 6500 rpm으로 10분 동안 원심분리한 후 상등액을 0.2 ㎛ 주사기 필터(Fisher Scientific, Pittsburgh, USA)로 여과하여 갈색거저리 물 추출물을 제조하였다.
100 mL of distilled water and twice the volume of brown goat ( Tenebrio molitor ) were mixed and heated for 15 minutes at a temperature of 110 ° C and a pressure of 0.4 kg force /
<시험예><Test Example>
마우스 준비Mouse preparation
골질환 개선, 예방 또는 치료용 조성물로서의 효과를 검증하기 위해 많은 연구가 진행되고 있으나 사람을 대상으로 하는 연구에는 한계가 있기 때문에 대부분 동물을 이용하고 있다. 그 가운데 폐경기 후 골질환의 표본으로 가장 많이 이용되는 모델이 난소를 적출한 마우스인데, 이는 난소적출 마우스가 초기 폐경여성의 특징과 상당히 비슷하기 때문에, 골질환 개선, 예방 또는 치료용 조성물로 연구에서 많이 이용된다.Many studies have been conducted to verify the effectiveness of the composition as a composition for improving, preventing or treating bone diseases. However, most studies on human subjects have limitations and most animals are used. Among them, the ovariectomized mouse is the most commonly used model of post-menopausal bone disease because ovariectomized mice are very similar to those of early postmenopausal women, It is widely used.
실험동물은 8주령의 DDY 암컷 마우스(평균 중량 28 g) 40마리를 코아텍(KOATECH, Pyeongtaeksi, Korea)으로부터 구입하였다. 실험 시작 전 1주일간 적응시킨 후 12시간 명암주기(light cycle from 7:00-19:00) 하에서 상온(22±1 ℃) 및 60% 습도로 사육하였다. Forty male DDY female mice (average weight 28 g) at 8 weeks of age were purchased from KOATECH (Pyeongtaeksi, Korea). The animals were housed at room temperature (22 ± 1 ° C) and 60% humidity for 12 weeks at light cycle from 7: 00-19: 00.
경구투여 시작 3일 전에 20마리는 대조군으로서 난소 적출 없이 단순 개복 후 봉합(non-OVX)하였고, 다른 20마리는 난소 적출술(OVX: ovariectomy)을 시행하였다. 수술 후 2일 동안 항생제(Baytril, Bayer Korea, Ansansi, Korea)를 0.9% 생리식염수에 4배 희석한 것을 피하주사하였으며, 40마리의 마우스를 10마리씩 총 4개 군으로 분리하였다. 증류수와 갈색거저리 추출물을 마우스용 존대(Φ1.5*70 mm)를 이용하여 10 ml/1 kg/1 day 용량으로 투여시작일(day 1)로부터 8주간 매일 경구투여하였다.Three days before the start of oral administration, 20 animals were treated as non-OVX without ovariectomy and 20 as ovariectomy (OVX: ovariectomy). After 2 days of operation, antibiotics (Baytril, Bayer Korea, Ansansi, Korea) were diluted 4 times in 0.9% physiological saline and subcutaneously injected. Forty mice were divided into 4 groups. Distilled water and brown goat extract were orally administered daily for 8 weeks starting from the day of administration (day 1) at a dose of 10 ml / kg / day using a mouse mouse (Φ1.5 * 70 mm).
본 실험에 사용한 모든 시험물질은 매일 동일한 시간에 경구 투여하였다. All test materials used in this experiment were orally administered at the same time every day.
상기 마우스와 관련된 모든 절차는 순천향대학교의 기관동물관리 및 사용위원회(IACUC approval no. SCH15-0001)의 윤리적 기준에 따라 수행하였다.All procedures related to the mice were performed in accordance with the ethical standards of the IACUC approval No. SCH15-0001 of Soonchunhyang University.
-4개 군의 마우스-Four groups of mice -
A(NON/DW): non-OVX,일반 식이(2018S; Harlan, USA) + 증류수(DW) 10 ml/kg무게를 혼합한 식이군 10마리A total of 10 dogs were weighed 10 ml / kg of non-OVX, normal diet (2018S; Harlan, USA) and distilled water (DW)
B(NON/TM): non-OVX, 일반 식이(2018S; Harlan, USA) + 실시예 1의 갈색거저리 추출물 0.2 g/kg무게를 혼합한 식이군 10마리B (NON / TM): non -OVX, the general formula (2018S; Harlan, USA) + Example 1 of the mealworm expression extract a mixture of 0.2 g / kg weight of the group of 10 animals
C(OVX/DW): OVX, 일반 식이(2018S; Harlan, USA) + 증류수(DW) 10 ml/kg무게을 혼합한 식이군 10마리C (OVX / DW): OVX , the general formula (2018S; Harlan, USA) + distilled water (DW) expression is a mixture of 10 ml / kg weight of the group of 10 animals
D(OVX/TM): OVX, 일반 식이(2018S; Harlan, USA) + 실시예 1의 갈색거저리 추출물 0.2 g/kg무게를 혼합한 식이군 10마리
D (OVX / TM): OVX , the general formula (2018S; Harlan, USA) + Example 1 of the mealworm expression extract a mixture of 0.2 g / kg weight of the group of 10 animals
시험예 1. 체중 측정Test Example 1. Body weight measurement
도 1A는 마우스에 식이를 28일 동안 섭취시켜 변화된 체중을 나타낸 그래프이며, 도 1B는 8주 동안 마우스가 섭취한 식이의 양을 나타낸 그래프이고, 도 1C는 8주 동안 마우스의 혈당 수준을 나타낸 그래프이다. 체중 증가량과 사료 및 음수 섭취량을 매일 측정하였고, 혈당은 매주 1회 측정하였다. FIG. 1B is a graph showing the amount of diet consumed by the mouse for 8 weeks, FIG. 1C is a graph showing the blood glucose level of the mouse for 8 weeks, and FIG. to be. Weight gain, feed and water intake were measured daily, and blood glucose was measured once a week.
마우스에 식이를 섭취시킨 8주 동안 일정시각에 체중변화를 측정하였으며, 일정시각에 식이섭취량(식이섭취량=급여량-잔량)을 측정하였다. The body weight change was measured at a certain time for 8 weeks after feeding the mice, and the dietary intake (dietary intake = feeding amount - residual amount) was measured at a certain time.
도 1A 내지 도 1C에 나타낸 바와 같이, Non-OVX 마우스 군에서는 DW 또는 TM의 투여에 상관없이 몸무게 증가량에 차이가 없었으나, OVX 마우스 군에서는 TM을 투여한 군(OVX/TM)이 DW를 투여한 군(OVX/DW)보다 몸무게 증가량이 매우 높은 것을 확인하였다. As shown in FIGS. 1A to 1C, in the non-OVX mouse group, there was no difference in the weight increase regardless of the administration of DW or TM, but in the OVX mouse group, the group administered with TM (OVX / TM) (OVX / DW) than those of one group (OVX / DW).
또한, 전체적으로 모든 마우스 군에서 식이 섭취량에 특별한 차이가 없는 것으로 보아 OVX/TM 군의 뛰어난 몸무게 증가율은 식이 섭취량의 증가로 인한 것이 아니며, TM의 지속적인 경구 투여가 난소 적출술(OVX) 이후의 회복력에 있어 매우 긍정적인 효과를 가질 수 있음을 의미한다. In addition, overall, there was no significant difference in dietary intake among all groups of mice. The excellent weight gain rate of the OVX / TM group was not due to an increase in dietary intake, and continuous oral administration of TM was associated with recovery after ovariectomy (OVX) It can have a very positive effect.
한편, 혈당 수치는 각 군 사이에서 유의한 차이가 나타나지 않았다.
On the other hand, blood glucose levels did not show any significant difference among the groups.
시험예Test Example 2. 2. 뼈조직의Bony 헤마톡실린&에오신 염색( Hematoxylin & eosin staining ( HematoxylinHematoxylin &Eosin staining) & Eosin staining)
도 2A는 Non-OVX_DW(NON/DW) 마우스 군의 골단(epiphysis)을 헤마톡실린&에오신으로 염색한 사진이며, 도 2B는 Non-OVX_TM(NON/TW) 마우스 군의 골단(epiphysis)을 헤마톡실린&에오신으로 염색한 사진이고, 도 2C는 OVX_DW 마우스 군의 골단(epiphysis)을 헤마톡실린&에오신으로 염색한 사진이며, 도 2D는 OVX_TM 마우스 군의 골단(epiphysis)을 헤마톡실린&에오신으로 염색한 사진이다. 또한, 도 2E는 각 마우스군 넓적다리뼈의 골피질(cortical bone) 두께를 나타낸 그래프이며, 도 2F는 각 마우스군 넓적다리뼈의 뼈기둥(trabecular bone)의 부피를 나타낸 그래프이다.FIG. 2A is a photograph of the epiphysis of Non-OVX_DW (NON / DW) mouse group stained with hematoxylin and eosin, and FIG. 2B is a photograph showing the epiphysis of Non-OVX_TM FIG. 2C is a photograph of the epiphysis of OVX_DW mouse group stained with hematoxylin and eosin, FIG. 2D shows the epiphysis of OVX_TM mouse group with hematoxylin and eosin . FIG. 2E is a graph showing the thickness of the cortical bone of each mouse group, and FIG. 2F is a graph showing the volume of the trabecular bone of each mouse group.
마우스를 희생시킨 후 각 마우스의 넓다리뼈(femur)와 정강이뼈(tibia)를 적출하여 8% formic acid 용액에서 3일간 탈회한 후 탈수, 투명화 및 침투과정을 거쳐 파라핀블록을 제조하였다. 각 파라핀 블록을 4 um 두께로 박절하여 제조된 조직 슬라이드를 크실렌(xylene) 용액에 담가 파라핀을 제거하고 곧바로 하강계열 에탄올에 담가 함수시킨 뒤 Harris Hematoxylin Solution Modified(Sigma Aldrich, MO, USA)과 Eosin Y Solution Aqueous(Sigma Aldrich, MO, USA) 용액에 염색시켰다. 다시 상승계열 에탄올과 xylene 용액에 차례로 담근 후 봉입하여 현미경으로 관찰하였다. After the mice were sacrificed, the wide femur and tibia of each mouse were excised and demineralized in 8% formic acid solution for 3 days, followed by dewatering, transparency and infiltration to produce paraffin blocks. Each paraffin block was cut into 4-μm thick tissue slides were immersed in xylene solution to remove paraffin and immediately immersed in descending ethanol. After that, Harris Hematoxylin Solution Modified (Sigma Aldrich, MO, USA) and Eosin Y Solution Aqueous (Sigma Aldrich, MO, USA). Then, the cells were immersed in ascending ethanol and xylene solution, and then they were observed by a microscope.
각 군 당 5마리 마우스의 뼈조직 슬라이드를 각각 현미경 상에서 관찰하여 총 6가지 항목에 대한 통계분석을 실시하였다. TBV(Trabecular bone volume)은 bone volume/trabecular bone volume으로 상대적인 측정값이고, Tbn(trabecular bone number)은 조직 슬라이드 평면상에서 확인할 수 있는 골주 단면의 개수를 측정한 것이다. 또한, Tbl(Trabecular bone length)와 Tbt(trabecular bone thickness)는 각각 넓다리뼈(femur) 말단 사이의 종단면과 넓다리뼈(femur) 중심부에서의 횡단면의 길이를 측정한 것이며, Cbt(cortical bone thickness)는 조직 슬라이드 평면상에서 나타나는 넓다리뼈(femur) 중심부에서의 두 개의 치밀뼈 두께를 측정한 것이다, 한편, 넓다리뼈(femur) 말단에서의 파골세포의 개수(Ocn)도 측정하였다. 상기 6가지 항목에 대한 값은 하기 표 1에 나타내었다.Bone tissue slides of 5 mice per each group were observed under a microscope, and statistical analysis was performed on 6 items. Trabecular bone volume (TBV) is the relative measure of bone volume / trabecular bone volume, and Tbn (trabecular bone number) is the number of vertebral facets that can be identified on the tissue slide plane. Trabecular bone length and Tbt (trabecular bone thickness) are each broad. The length of the cross-section between the femur ends and the center of the femur is measured. Cbt (cortical bone thickness) The thickness of the two dense bones at the center of the femur was measured, while the number of osteoclasts (Ocn) at the femur end was also measured. Values for the above six items are shown in Table 1 below.
(%)TBV
(%)
(number)Tbn
(number)
(mm)Tbl
(mm)
(um)Tbt
(um)
(um)Cbt
(um)
(number)Ocn
(number)
Tbn=Trabecular bone number (N/epiphyseal)
Tbl=Trabecular bone length (Longitudinal thickness; mm)
Tbt=Trabecular bone thickness (Cross thickness; m)
Cbt=Cortical bone thickness (Cross thickness; m)
Ocn=Osteoclast cell number (N/epiphyseal)TBV = Trabecular bone volume (%), BV / TV
Tbn = Trabecular bone number (N / epiphyseal)
Tbl = Trabecular bone length (mm)
Tbt = Trabecular bone thickness (Cross thickness; m)
Cbt = Cortical bone thickness (Cross thickness; m)
Ocn = Osteoclast cell number (N / epiphyseal)
도 2 및 표 1에 나타낸 바와 같이, 난소적출 후 골소실이 유발된 OVX 마우스 군(OVX/DW 및 OVX/TM)이 Non-OVX 마우스 군(NON/DW 및 NON/TW)에 비하여 TBV, Tbn, Tbl, Tbt 및 Cbt 수치가 모두 낮으며, 반대로 Ocn 수치는 높은 것을 확인하였다. 이는 마우스에서 난소를 적출한 후 형성된 폐경기의 생체환경에 의한 골다공증 유사 모델을 만듦으로써 예상했던 결과와 일치하였다. 특히, 파골세포(osteoclast, Ocn) 수의 증가로 인한 뼈재흡수 증가는 골다공증을 나타내는 중요한 지표가 된다. OVX mice (OVX / DW and OVX / TM) in which osteolysis was induced after ovariectomy were compared with non-OVX mice (NON / DW and NON / TW) , Tbl, Tbt and Cbt values were all low, while the Ocn values were high. This was consistent with the expected results of making osteoporosis-like models of the postmenopausal vital environment after ovariectomy in mice. In particular, increased bone resorption due to increased osteoclast (Ocn) counts is an important indicator of osteoporosis.
또한, OVX 마우스 군에서는 TM을 투여한 군(OVX/TM)이 DW를 투여한 군(OVX/DW)에 비하여 TBV, Tbn, Tbl, Tbt 및 Cbt 수치가 높고 Ocn 수치가 낮으므로 골다공증이 완화되는 것을 확인하였다. 이는 OVX 마우스 군에서 TM의 지속적인 투여가 뼈의 길이성장, 밀도 및 두께를 증가시켜줄 뿐만 아니라, 파골세포의 수를 감소시켜 뼈의 재흡수를 억제시킨다는 것을 의미한다.In OVX mouse group, ovariectomy was alleviated due to high levels of TBV, Tbn, Tbl, Tbt, and Cbt and low Ocn levels compared with the group treated with OVX / TM (OVX / TM) Respectively. This implies that continuous administration of TM in the OVX mouse group not only increases bone length growth, density and thickness, but also reduces the number of osteoclasts and inhibits bone resorption.
반면, Non-OVX 마우스 군에서는 DW를 투여한 군(Non-OVX_DW)과 TM을 투여한 군(Non-OVX_TM)이 상기 각 항목에서 유사한 수치를 보였다.
In the non-OVX mouse group, non-OVX_DW and TM-treated groups (Non-OVX_TM) showed similar values in the above items.
하기에 본 발명의 분말을 함유하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, formulation examples of the composition containing the powder of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.
제제예 1. 산제의 제조Preparation Example 1. Preparation of powder
실시예 1에서 얻은 추출물 분말 500 mg500 mg of the extract powder obtained in Example 1
유당 100 mgLactose 100 mg
탈크 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.
The above components are mixed and filled in airtight bags to prepare powders.
제제예 2. 정제의 제조Formulation Example 2. Preparation of tablets
실시예 1에서 얻은 추출물 분말 300 mg300 mg of the extract powder obtained in Example 1
옥수수전분 100 mgCorn starch 100 mg
유당 100 mgLactose 100 mg
스테아린산 마그네슘 2 mg
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.
After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.
제제예 3. 캅셀제의 제조Formulation Example 3. Preparation of capsules
실시예 1에서 얻은 추출물 분말 200 mg200 mg of the extract powder obtained in Example 1
결정성 셀룰로오스 3 mg
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.
The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.
제제예 4. 주사제의 제조Formulation Example 4. Preparation of injection
실시예 1에서 얻은 추출물 분말 600 mg600 mg of the extract powder obtained in Example 1
만니톨 180 mg180 mg mannitol
주사용 멸균 증류수 2974 mgSterile sterilized water for injection 2974 mg
Na2HPO4,12H2O 26 mgNa 2 HPO 4 , 12H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플 당 상기의 성분 함량으로 제조한다.
It is prepared by the above-mentioned component content per ampoule according to the usual injection preparation method.
제제예 5. 액제의 제조Formulation Example 5. Preparation of a liquid preparation
실시예 1에서 얻은 추출물 분말 4 g4 g of the extract powder obtained in Example 1
이성화당 10 g10 g per isomer
만니톨 5 g5 g mannitol
정제수 적량Purified water quantity
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100g으로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.
Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 g with purified water, To prepare a liquid agent.
제제예 6. 과립제의 제조Preparation Example 6 Preparation of Granules
실시예 1에서 얻은 추출물 분말 1,000 mg1,000 mg of the extract powder obtained in Example 1
비타민 혼합물 적량Vitamin mixture quantity
비타민 A 아세테이트 70 ㎍70 [mu] g of vitamin A acetate
비타민 E 1.0 mgVitamin E 1.0 mg
비타민 B1 0.13 mgVitamin B1 0.13 mg
비타민 B2 0.15 mg0.15 mg of vitamin B2
비타민 B6 0.5 mgVitamin B6 0.5 mg
비타민 B12 0.2 ㎍0.2 [mu] g vitamin B12
비타민 C 10 mg
비오틴 10 ㎍Biotin 10 μg
니코틴산아미드 1.7 mgNicotinic acid amide 1.7 mg
엽산 50 ㎍50 ㎍ of folic acid
판토텐산 칼슘 0.5 mgCalcium pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture quantity
황산제1철 1.75 mg1.75 mg of ferrous sulfate
산화아연 0.82 mg0.82 mg of zinc oxide
탄산마그네슘 25.3 mgMagnesium carbonate 25.3 mg
제1인산칼륨 15 mgPotassium monophosphate 15 mg
제2인산칼슘 55 mg
구연산칼륨 90 mgPotassium citrate 90 mg
탄산칼슘 100 mgCalcium carbonate 100 mg
염화마그네슘 24.8 mgMagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 과립제에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 과립제 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능식품 조성물 제조에 사용할 수 있다.
The composition ratio of the above-mentioned vitamins and minerals is comparatively comparatively mixed with the granules according to the preferred embodiment. However, the blending ratio may be arbitrarily changed, and the above components are mixed according to the ordinary granule preparation method, Can be prepared and used in the manufacture of a health functional food composition according to a conventional method.
제제예Formulation example 7. 기능성 음료의 제조 7. Manufacture of functional beverages
실시예 1에서 얻은 추출물 분말 1,000 mg 1,000 mg of the extract powder obtained in Example 1
구연산 1,000 mgCitric acid 1,000 mg
올리고당 100 g100 g of oligosaccharide
매실농축액 2 gPlum concentrate 2 g
타우린 1 gTaurine 1 g
정제수를 가하여 전체 900 mLPurified water was added to the flask to obtain a total of 900 mL
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1 시간 동안 85 ℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 L 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 기능성 음료 조성물 제조에 사용한다. The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The solution thus prepared was filtered and sterilized in a sterilized 2 L container, It is used in the production of the functional beverage composition of the invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the compounding ratio may be arbitrarily varied depending on the regional and national preferences such as the demand level, the demanding country, and the intended use.
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| KR102044228B1 (en) | 2019-05-28 | 2019-11-13 | 영월군 | Isolating Method for Compounds having Antioxidant Ability from Adults of Tenebrio molitor |
| KR102076459B1 (en) | 2019-10-29 | 2020-02-13 | 주식회사 한미양행 | Composition containing enzyme treatmented Tenebrio molitor for muscle mass enhancement and restorative rejuvenation of recovering patients or elderly patients |
| KR20200046773A (en) * | 2018-10-25 | 2020-05-07 | 대한민국(농촌진흥청장) | Composition comprising Locusta migratoria extract for promoting osteoblast differentiation |
| KR20210007401A (en) * | 2019-07-11 | 2021-01-20 | 대한민국(농촌진흥청장) | Pharmaceutical composition for enhancing osteogenesis comprising Tenebrio molitor oil |
| KR20210060983A (en) * | 2019-11-19 | 2021-05-27 | 대한민국(농촌진흥청장) | Locusta Migratoria ethanol extract for inhibiting osteoclast differentiation and uses therof |
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| KR102185436B1 (en) | 2018-10-25 | 2020-12-01 | 대한민국 | Composition comprising Locusta migratoria extract for promoting osteoblast differentiation |
| KR102044228B1 (en) | 2019-05-28 | 2019-11-13 | 영월군 | Isolating Method for Compounds having Antioxidant Ability from Adults of Tenebrio molitor |
| KR20210007401A (en) * | 2019-07-11 | 2021-01-20 | 대한민국(농촌진흥청장) | Pharmaceutical composition for enhancing osteogenesis comprising Tenebrio molitor oil |
| KR102253131B1 (en) | 2019-07-11 | 2021-05-18 | 대한민국 | Pharmaceutical composition for enhancing osteogenesis comprising Tenebrio molitor oil |
| KR102076459B1 (en) | 2019-10-29 | 2020-02-13 | 주식회사 한미양행 | Composition containing enzyme treatmented Tenebrio molitor for muscle mass enhancement and restorative rejuvenation of recovering patients or elderly patients |
| KR20210060983A (en) * | 2019-11-19 | 2021-05-27 | 대한민국(농촌진흥청장) | Locusta Migratoria ethanol extract for inhibiting osteoclast differentiation and uses therof |
| KR102292696B1 (en) | 2019-11-19 | 2021-08-24 | 대한민국 | Locusta Migratoria ethanol extract for inhibiting osteoclast differentiation and uses therof |
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