KR102070312B1 - COMPOSITION FOR BONE GROWTH PROMOTING COMPRISING Allium fistulosum L. AS AN ACTIVE INGREDIENT - Google Patents
COMPOSITION FOR BONE GROWTH PROMOTING COMPRISING Allium fistulosum L. AS AN ACTIVE INGREDIENT Download PDFInfo
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- KR102070312B1 KR102070312B1 KR1020180048595A KR20180048595A KR102070312B1 KR 102070312 B1 KR102070312 B1 KR 102070312B1 KR 1020180048595 A KR1020180048595 A KR 1020180048595A KR 20180048595 A KR20180048595 A KR 20180048595A KR 102070312 B1 KR102070312 B1 KR 102070312B1
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- Prior art keywords
- growth
- plate expansion
- bone length
- extract
- bone
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Classifications
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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
- 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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8962—Allium, e.g. garden onion, leek, garlic or chives
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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
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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
본 발명은 총백 추출물을 유효성분으로 포함하는 뼈 성장 촉진용 조성물에 관한 것이다. 이에 의하여, 본 발명의 총백 추출물을 포함하는 뼈 성장 촉진용 조성물은 성장기에 있는 어린이나 청소년에 의약, 식품 등으로 투여할 경우 성장기에 있는 어린이나 청소년의 골길이 성장, 성장판 확장에 의해 뼈 성장을 촉진시킬 뿐 아니라, 골밀도 또한 유지하거나 높이는 효과가 있다.The present invention relates to a composition for promoting bone growth comprising the extract of baekbaek as an active ingredient. As a result, the composition for promoting bone growth comprising the extract of the total back of the present invention, when administered as a medicine, food, etc. to children or adolescents in the growth phase bone growth by the growth of bone length of the children or adolescents in the growth phase, growth plate expansion In addition to promoting, bone density is also effective to maintain or increase.
Description
본 발명은 총백(Allium fistulosum L.) 추출물을 유효성분으로 포함하는 뼈 성장 촉진용 조성물에 관한 것으로, 더욱 상세하게는 성장기의 소아나 청소년이 투여하거나 섭취함으로써 뼈 성장을 촉진시킬 수 있는 약학 또는 식품 조성물에 관한 것이다.The present invention is a total bag ( Allium) It relates to a composition for promoting bone growth comprising the fistulosum L. ) extract as an active ingredient, and more particularly, to a pharmaceutical or food composition that can promote bone growth by administering or ingesting children or adolescents during the growth phase.
교육열과 성장에 대한 관심이 높아지면서 부모들의 아이의 성장에 대한 관심이 높아지고 있다. 특히 발육, 키 성장에 대한 관심이 높아지는데 병원에서 아이들의 성장판 검사에 대한 항목이 필수로 들어갈 정도로 아이 성장에 대한 관심이 높다. As the enthusiasm for education and growth is growing, interest in the growth of parents' children is increasing. In particular, the interest in growth and height growth is increasing, and the interest in the growth of children is high enough that items for the growth plate examination of children in hospitals are essential.
뼈는 칼슘과 인으로 이루어진 조직으로 인산칼슘복염, 콜라겐 섬유, glycoprotein, proteoglycan 이 주 구성물이며, 몸을 구성하고 지탱하는 역할을 수행하는 기관이다. 내부의 장기를 보호하는 역할을 수행하고 근육이 움직일 수 있도록 지탱하는 역할을 하며, 사람이 형태를 구성하고 유지하는 역할도 수행하지만, 뼈 속 골수에서는 몸의 산소운반체인 혈액을 생성할 수 있다. Bone is a tissue composed of calcium and phosphorus, and calcium phosphate complex, collagen fiber, glycoprotein, and proteoglycan are the major constituents, and the organs that support and support the body. It plays a role in protecting internal organs, supporting muscle movement, and in forming and maintaining a human form, but bone marrow can produce blood, the body's oxygen carrier.
뼈세포의 유형 중 하나인 조골 세포는 콜라겐과 알칼리인산분해효소를 분비하여 뼈를 형성하는 역할을 수행하는데, 알칼리인산분해효소의 경우 어떠한 기능을 수행하는지에 대해 아직 알려져 있지 않으나 뼈세포 생성이 높은 환자들의 혈장 내에서 높은 수치를 나타내는 것으로 알려져 있다. 또한, 파골세포는 뼈를 파괴하는 세포로 뼈를 분해하여 인산과 칼슘을 혈장으로 흘려보내는 역할을 수행한다. Osteoblasts, one of the types of bone cells, secrete collagen and alkaline phosphatase to form bones. Alkaline phosphatase does not know what function it performs but it is not known to produce high bone cells. It is known to show high levels in the plasma of patients. In addition, osteoclasts are cells that destroy bones, and break down bones to serve to release phosphate and calcium into plasma.
골 성장은 파골세포와 조골세포의 상호작용에 의해 이루어지는데, 파골세포에 의해 골이 흡수되면 조골세포는 다시 칼슘과 인을 조합하면서 골 성장이 이루어질 수 있다. 조골세포의 활성이 파골세포보다 높을 경우 골 성장이 이루어지며, 반대의 경우에는 골 파괴가 이루어져 골다공증을 일으킬 수 있다. 조골세포의 활성이 파골세포 보다 높아지는 경우는 성장호르몬이 분비되는 시기로 주로 성장기 아동이나 청소년기를 들 수 있다. Bone growth is made by the interaction of osteoclasts and osteoblasts, when bone is absorbed by osteoclasts, osteoblasts can be made again by combining calcium and phosphorus. If osteoblast activity is higher than osteoclasts, bone growth occurs, and in the opposite case, bone destruction occurs, which can lead to osteoporosis. When osteoblast activity is higher than osteoclasts, growth hormone is secreted at the growth stage of the child or adolescence.
뼈를 구성하는 주요소인 칼슘과 인은 뼈를 구성할 때는 두 이온이 복합체를 이루어 존재하지만 이동할 때는 혈청에서 이온화 된 형태로 존재한다. 혈중 칼슘이온의 농도에 따라서도 칼슘 재흡수가 증가되거나 배설이 되면서 항상성이 유지된다.Calcium and phosphorus, two major constituents of bone, exist in the form of two ions in the bone, but in ionized form when moved. Depending on the concentration of calcium ions in the blood, calcium resorption is increased or excreted and homeostasis is maintained.
한편, 성장에 영향을 주는 호르몬으로는 인슐린, 갑상선호르몬, 성 호르몬이 있는데 그 중에서 성장호르몬은 뇌하수체 전엽에서 분비되는 호르몬으로, 신체를 성장시키고, 뼈의 석회화를 촉진하며, 단백질 합성량 증가, 면역작용 촉진 등의 역할을 수행한다. 성장의 주 동력원인 뇌가 사용할 수 있는 에너지원이 포도당이기 때문에 성장 호르몬은 혈당과 연관성이 있다. 성장 호르몬이 과다하게 분비될 경우 지속적으로 혈중 당의 농도가 높아져 당뇨를 유발할 수도 있다.On the other hand, the hormones that affect growth include insulin, thyroid hormones and sex hormones, among which hormones are secreted from the anterior pituitary gland, which grows the body, promotes bone calcification, increases the amount of protein synthesis, and immunity. It plays a role in promoting action. Growth hormone is associated with blood sugar because glucose is the energy source available to the brain, the main driver of growth. Excessive growth hormone secretion can lead to high blood sugar levels, which can lead to diabetes.
성장기 아동의 육체적 건강에 도움을 주고, 대사성 질환 및 비만 유도를 방지하며 부작용이 없는 성장 호르몬 개선제에 대한 연구가 지속적으로 필요한 실정이다.There is a continuing need for research on growth hormone improvers that help physical health of growing children, prevent metabolic diseases and obesity, and have no side effects.
본 발명의 목적은 상술한 문제점을 해결하기 위한 것으로 성장기에 있는 어린이나 청소년에 의약, 식품 등으로 투여할 경우 대사성 질환이나 비만 유도의 부작용 없이 성장기에 있는 어린이나 청소년의 골길이 성장, 성장판 확장에 의해 뼈 성장을 촉진시킬 뿐 아니라, 골밀도 또한 유지하거나 높이는 효과가 있는 총백 추출물을 포함하는 뼈 성장 촉진용 조성물을 제공하는 데 있다.An object of the present invention is to solve the above-mentioned problems, when administered to children or adolescents in the growth phase as a medicine, food, etc. in bone growth and growth plate growth of children or adolescents in the growth phase without side effects of metabolic disease or obesity induction Not only to promote bone growth, but also to provide a composition for promoting bone growth comprising a total back extract effective in maintaining or increasing bone density.
본 발명의 하나의 측면에 따르면,According to one aspect of the invention,
총백 추출물을 유효성분으로 포함하는 뼈 성장 촉진용 약학 조성물이 제공된다.Provided is a pharmaceutical composition for promoting bone growth, comprising a baekbaek extract as an active ingredient.
상기 총백 추출물은 물, 탄소수 1-4의 알코올, 또는 이들의 혼합용매에 의해 추출된 것일 수 있다.The total bag extract may be extracted by water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
상기 약학 조성물은 과립제, 산제, 정제, 피복정, 캡슐제, 액제, 시럽, 즙, 현탁제, 유제, 점적제 및 주사 액제 중에서 선택된 어느 하나의 제제로 제조된 것일 수 있다.The pharmaceutical composition may be prepared from any one of granules, powders, tablets, coated tablets, capsules, solutions, syrups, juices, suspensions, emulsions, drops and injection solutions.
상기 약학 조성물은 TGF-β(Transforming growth factor beta) 수용체 및 wnt 수용체 중에서 선택된 1종 이상의 신호전달을 향상시켜 골 성장을 유도하는 것일 수 있다.The pharmaceutical composition may be to induce bone growth by enhancing one or more signaling selected from a transforming growth factor beta (TGF-β) receptor and a wnt receptor.
상기 약학 조성물은 성장기 어린이 또는 청소년의 뼈 성장 촉진용일 수 있다.The pharmaceutical composition may be for promoting bone growth of growing children or adolescents.
상기 약학 조성물은 비만인 성장기 어린이 또는 청소년의 뼈 성장 촉진용일 수 있다.The pharmaceutical composition may be for promoting bone growth of obese growth children or adolescents.
본 발명의 다른 하나의 측면에 따르면,According to another aspect of the invention,
총백 추출물을 유효성분으로 포함하는 뼈 성장 촉진용 식품 조성물이 제공된다.Provided is a food composition for promoting bone growth, which comprises a total back extract as an active ingredient.
상기 총백 추출물은 물, 탄소수 1-4의 알코올, 또는 이들의 혼합용매에 의해 추출된 것일 수 있다.The total bag extract may be extracted by water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
상기 식품 조성물은 TGF-β(Transforming growth factor beta) 수용체 및 wnt 수용체 중에서 선택된 1종 이상의 신호전달을 향상시켜 골 성장을 유도하는 것일 수 있다.The food composition may be to induce bone growth by enhancing one or more signaling selected from a transforming growth factor beta (TGF-β) receptor and a wnt receptor.
상기 식품 조성물은 성장기 어린이 또는 청소년의 뼈 성장 촉진용일 수 있다.The food composition may be for promoting bone growth of growing children or adolescents.
상기 식품 조성물은 비만인 성장기 어린이 또는 청소년의 뼈 성장 촉진용일 수 있다.The food composition may be for promoting bone growth of obese children or adolescents.
상기 식품 조성물은 과립제, 산제, 정제, 피복정, 캡슐제, 액제, 시럽, 즙, 현탁제, 및 유제 중에서 선택된 어느 하나의 제제로 제조된 것일 수 있다.The food composition may be prepared from any one of granules, powders, tablets, coated tablets, capsules, solutions, syrups, juices, suspensions, and emulsions.
본 발명의 다른 또 하나의 측면에 따르면,According to another aspect of the invention,
상기 식품 조성물을 포함하는 뼈 성장 촉진용 건강기능식품을 제공한다.It provides a health functional food for promoting bone growth comprising the food composition.
상기 건강기능식품은 음료, 차류, 향신료, 껌 및 과자류 중에서 선택된 어느 하나의 식품 소재에 상기 총백 추출물을 첨가하여 제조된 것일 수 있다.The health functional food may be prepared by adding the extract of baekbaek to any one food material selected from beverages, teas, spices, gum and confectionery.
본 발명의 다른 또 하나의 측면에 따르면,According to another aspect of the invention,
총백을 물, 탄소수 1-4의 알코올, 또는 이들의 혼합용매에 의해 추출하여 총백 추출물을 제조하는 단계를 포함하는 뼈 성장 촉진용 약학 조성물의 제조방법이 제공된다.Provided is a method for preparing a pharmaceutical composition for promoting bone growth, comprising extracting a total bag with water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof to prepare a total bag extract.
상기 단계 이후 감압 농축하는 단계를 추가로 수행할 수 있다.Concentration under reduced pressure may be further performed after the step.
본 발명의 다른 또 하나의 측면에 따르면,According to another aspect of the invention,
총백을 물, 탄소수 1-4의 알코올, 또는 이들의 혼합용매에 의해 추출하여 총백 추출물을 제조하는 단계를 포함하는 뼈 성장 촉진용 식품 조성물의 제조방법이 제공된다.Provided is a method for preparing a food composition for promoting bone growth, comprising the step of extracting the total bag with water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof to produce the total bag extract.
상기 단계 이후 감압 농축하는 단계를 추가로 수행할 수 있다.Concentration under reduced pressure may be further performed after the step.
본 발명의 다른 또 하나의 측면에 따르면,According to another aspect of the invention,
상기 식품 조성물을 음료, 차류, 향신료, 껌 및 과자류 중에서 선택된 어느 하나의 식품 소재에 첨가하여 건강기능식품을 제조하는 뼈 성장 촉진용 건강기능식품의 제조방법이 제공된다.Provided is a method for producing a health functional food for promoting bone growth, wherein the food composition is added to any one food material selected from beverages, teas, spices, gums and confectionery to produce health functional foods.
본 발명의 총백 추출물을 포함하는 뼈 성장 촉진용 조성물은 대사성 질환이나 비만 유도의 부작용 없이 성장기에 있는 어린이나 청소년에 의약, 식품 등으로 투여할 경우 성장기에 있는 어린이나 청소년의 골길이 성장, 성장판 확장에 의해 뼈 성장을 촉진시킬 뿐 아니라, 골밀도 또한 유지하거나 높이는 효과가 있다.Bone growth promoting composition comprising the extract of the present invention, bone length growth, growth plate expansion of children or adolescents in the growth phase when administered as a medicine, food, etc. to children or adolescents in the growth phase without side effects of metabolic disease or obesity induction In addition to promoting bone growth, bone density is also effective to maintain or increase.
도 1은 실험예 1에 따른 조골세포 MG63 cell의 MTT분석에 의한 세포 독성검사 결과이다.
도 2는 실험예 2에 따른 MG63 세포의 ALP 활성도 측정 결과이다.
도 3 및 도 4는 실험예 3에 따른 TGF-β 신호전달 관련 유전자의 mRNA 발현 분석 결과를 나타낸 것이다.
도 5 및 도 6은 실험예 4에 따른 wnt 신호전달 관련 유전자의 mRNA 발현 분석 결과를 나타낸 것이다.
도 7은 실험예 5에 따른 식이 공급 후 백서의 체중 측정 결과를 나타낸 것이다.
도 8은 실험예 6에 따른 백서의 정강뼈(tibia)의 길이 성장 효과 분석 결과이다.
도 9는 실험예 6에 따른 백서의 넙다리뼈(femur)의 길이 성장 효과 분석 결과이다.
도 10은 실험예 7에 따른 백서의 관절 부위에 있는 성장판을 H-E로 염색한 현미경 이미지이다.
도 11은 실험예 7에 따른 성장판에서 증식부의 길이를 비교한 그래프이다.
도 12는 실험예 7에 따른 성장판에서 비대부의 길이를 비교한 그래프이다.
도 13은 실험예 7에 따른 관절 전체 길이를 비교한 그래프이다.
도 14는 실험예 8에 따른 요추(Lumbar spine)의 골밀도 변화를 측정한 결과이다.
도 15는 실험예 8에 따른 넙다리뼈(femur)의 골밀도 변화를 측정한 결과이다.
도 16은 실험예 9에 따른 혈청 내 ALP 농도를 측정한 결과이다.
도 17은 실험예 9에 따른 혈청 내 오스테오칼신(osteocalcin)의 농도를 측정한 결과이다.1 is a cytotoxicity test results by MTT analysis of osteoblast MG63 cells according to Experimental Example 1.
2 is a result of measuring the ALP activity of MG63 cells according to Experimental Example 2.
3 and 4 show the results of mRNA expression analysis of TGF-β signaling-related genes according to Experimental Example 3.
5 and 6 show the results of mRNA expression analysis of the gene associated with wnt signaling according to Experimental Example 4.
Figure 7 shows the weight measurement results of the white paper after the dietary supply according to Experimental Example 5.
8 is a result of analyzing the length growth effect of tibia of the white paper according to Experimental Example 6.
9 is a result of analyzing the growth effect of femur length of the white paper according to Experimental Example 6.
10 is a microscope image of HE staining of the growth plate in the joint region of the white paper according to Experimental Example 7.
Figure 11 is a graph comparing the length of the growth section in the growth plate according to Experimental Example 7.
12 is a graph comparing the length of the hypertrophy in the growth plate according to Experimental Example 7.
13 is a graph comparing the entire joint length according to Experimental Example 7. FIG.
14 is a result of measuring the bone density change of the lumbar spine (Lumbar spine) according to Experimental Example 8.
Figure 15 is the result of measuring the bone density change of femur according to Experimental Example 8.
16 is a result of measuring the concentration of ALP in serum according to Experimental Example 9.
Figure 17 is the result of measuring the concentration of osteocalcin (osteocalcin) in the serum according to Experimental Example 9.
본 발명은 다양한 변환을 가할 수 있고 여러 가지 실시예를 가질 수 있는 바, 특정 실시예들을 도면에 예시하고 상세한 설명에 상세하게 설명하고자 한다. 그러나, 이는 본 발명을 특정한 실시 형태에 대해 한정하려는 것이 아니며, 본 발명의 사상 및 기술 범위에 포함되는 모든 변환, 균등물 내지 대체물을 포함하는 것으로 이해되어야 한다. 본 발명을 설명함에 있어서 관련된 공지 기술에 대한 구체적인 설명이 본 발명의 요지를 흐릴 수 있다고 판단되는 경우 그 상세한 설명을 생략한다.
As the invention allows for various changes and numerous embodiments, particular embodiments will be illustrated in the drawings and described in detail in the written description. However, this is not intended to limit the present invention to specific embodiments, it should be understood to include all transformations, equivalents, and substitutes included in the spirit and scope of the present invention. In the following description of the present invention, if it is determined that the detailed description of the related known technology may obscure the gist of the present invention, the detailed description thereof will be omitted.
본 발명에 있어서, 상기 총백 추출물은 물, 유기용매 또는 이들의 혼합물을 추출 용매로서 이용하여 추출된 것일 수 있다. 이 때 사용되는 유기용매의 종류나 물과 유기용매의 혼합 비율은 특별히 제한되지 않는다. In the present invention, the total bag extract may be extracted using water, an organic solvent or a mixture thereof as an extraction solvent. The kind of organic solvent used at this time and the mixing ratio of water and an organic solvent are not specifically limited.
예를 들어, 상기 유기용매는 저급 알코올, 헥산, 아세톤, 에틸 아세테이트, 클로로포름, 및 디에틸에테르로 이루어진 군으로부터 선택된 하나 이상의 용매일 수 있다. 상기 저급 알코올은 탄소수 1 내지 6의 알코올일 수 있다. 예를 들어, 저급 알코올로는 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올, 노말-부탄올, 1-펜탄올, 2-부톡시에탄올 또는 에틸렌글리콜 등을 이용할 수 있다. 유기용매는 이 외에도 아세트산, DMFO(dimethyl-formamide), DMSO(dimethyl sulfoxide) 등의 극성 용매, 아세토나이트릴, 에틸 아세테이트, 메틸 아세테이트, 플루오로알칸, 펜탄, 2,2,4-트리메틸펜탄, 데칸, 사이클로헥산, 사이클로펜탄, 디이소부틸렌, 1-펜텐, 1-클로로부탄, 1-클로로펜탄, o-자일렌, 디이소프로필 에테르, 2-클로로프로판, 톨루엔, 1-클로로프로판, 클로로벤젠, 벤젠, 디에틸 에테르, 디에틸 설파이드, 클로로포름, 디클로로메탄, 1,2-디클로로에탄, 어닐린, 디에틸아민, 에테르, 사염화탄소 및 THF(Tetrahydrofuran) 등의 비극성 용매를 사용할 수도 있다.For example, the organic solvent may be one or more solvents selected from the group consisting of lower alcohols, hexane, acetone, ethyl acetate, chloroform, and diethyl ether. The lower alcohol may be an alcohol having 1 to 6 carbon atoms. For example, methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol, normal-butanol, 1-pentanol, 2-butoxyethanol or ethylene glycol may be used as the lower alcohol. Organic solvents include polar solvents such as acetic acid, dimethyl-formamide (DMFO) and dimethyl sulfoxide (DMSO), acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, 2,2,4-trimethylpentane, and decane. , Cyclohexane, cyclopentane, diisobutylene, 1-pentene, 1-chlorobutane, 1-chloropentane, o-xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene And nonpolar solvents such as benzene, diethyl ether, diethyl sulfide, chloroform, dichloromethane, 1,2-dichloroethane, anneal, diethylamine, ether, carbon tetrachloride, and THF (Tetrahydrofuran).
하기 실시예에서 확인할 수 있는 바와 같이, 총백을 유기용매로 추출할 경우 총백 추출물은 상층액과 하층액으로 분리되는데, 상층액은 총백 추출물의 오일 분획이며, 하층액은 일반적인 용매 추출물에 해당한다. 하층액을 다시 원심분리 또는 여과지를 통해 분리하면 액상과 고형 상태의 잔사로 나눠지는데 이 때의 잔사는 총백 추출물의 왁스 분획이다. 따라서, 본 발명의 총백 추출물은 총백 추출물의 오일 분획, 총백 추출물의 액상 분획, 총백 추출물의 왁스 분획을 모두 포함하는 개념으로 해석된다. 한 구체예에서, 상기 총백 추출물은 총백 추출물의 오일 분획, 총백 추출물의 액상 분획 및 총백 추출물의 왁스 분획으로 이루어진 군으로부터 선택된 어느 하나 이상을 포함할 수 있다.As can be seen in the following examples, when extracting the total bag with an organic solvent, the total bag extract is separated into a supernatant and a lower layer solution, the supernatant is an oil fraction of the total bag extract, and the lower layer solution corresponds to a general solvent extract. When the lower layer is separated again by centrifugation or filter paper, it is divided into a liquid phase and a solid residue, wherein the residue is the wax fraction of the total extract. Therefore, the baekbaek extract of the present invention is interpreted as a concept including both the oil fraction of baekbaek extract, the liquid fraction of baekbaek extract, the wax fraction of baekbaek extract. In one embodiment, the total bag extract may include any one or more selected from the group consisting of an oil fraction of the total bag extract, a liquid fraction of the total bag extract and a wax fraction of the total bag extract.
한 구체예에서, 상기 총백 추출물은 총백의 저급 알코올 추출물일 수 있으며, 바람직하게는 총백의 에탄올 추출물일 수 있다.In one embodiment, the total bag extract may be a lower alcohol extract of the total bag, preferably an ethanol extract of the total bag.
본 명세서에서 사용되는 용어 ‘추출물’은 추출물을 추가적으로 분획(fractionation)한 분획물도 포함한다. 즉, 총백 추출물은 상술한 추출용매를 이용하여 얻은 것뿐만 아니라, 여기에 정제과정을 추가적으로 적용하여 얻은 것도 포함한다. 또한, 상기 추출물이나 분획물을 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 얻은 분획, 다양한 크로마토그래피 (크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 총백 추출물에 포함된다.As used herein, the term 'extract' also includes fractions that additionally fractionate the extract. That is, the baekbaek extract includes not only obtained by using the above-described extraction solvent, but also obtained by additionally applying a purification process. In addition, fractions obtained by passing the extract or fraction through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), etc. Fractions obtained through the various purification methods described above are also included in the extract of the present invention.
한 구체예에서, 상기 총백 추출물은 총백의 유기용매 추출물을 제2의 유기용매로 재분획한 분획물일 수 있다. 여기에서, 총백의 유기용매 추출물이라 함은 광의로는 앞서 설명한 총백 추출물의 오일 분획, 총백 추출물의 액상 분획, 총백 추출물의 왁스 분획을 모두 포함하며, 협의로는 이 중 총백 추출물의 액상 분획을 의미한다. 그러므로, 한 구체예에서, 상기 총백의 유기 추출물을 제2의 유기용매로 재분획한 분획물은 총백 추출물의 액상 분획을 제2의 유기 용매로 재분획한 분획물을 의미할 수 있다. 다른 구체예에서, 상기 총백 추출물은 총백의 저급 알코올 추출물을 제2의 유기용매로 재분획한 분획물일 수 있다. 또다른 구체예에서, 상기 총백 추출물은 총백의 에탄올 추출물을 헥산으로 재분획한 분획물일 수 있다. 하기 실시예에서 살펴볼 수 있는 바와 같이, 이러한 총백의 지용성 성분이 다량 함유되어 있는 총백 추출물의 분획물은 매우 우수한 효과를 나타낸다.In one embodiment, the total bag extract may be a fraction obtained by re-fractionation of the organic solvent extract of the total bag with a second organic solvent. Here, the extract of the organic solvent of the total bag includes all of the oil fraction of the total bag extract, the liquid fraction of the total bag extract, and the wax fraction of the total bag extract, which broadly means the liquid fraction of the total bag extract. do. Therefore, in one embodiment, the fraction re-fractionated the organic extract of the total bag with a second organic solvent may mean a fraction re-fractionated the liquid fraction of the total bag extract with a second organic solvent. In another embodiment, the total bag extract may be a fraction obtained by re-fractionation of the lower alcohol extract of the total bag with a second organic solvent. In another embodiment, the total bag extract may be a fraction of the ethanol extract of the total bag re-fractionated with hexane. As can be seen in the following examples, fractions of the extract of the total bag containing a large amount of fat-soluble components of the total bag shows a very good effect.
본 명세서에서 총백을 언급하면서 사용되는 용어 ‘추출물’은 총백에 추출용매를 처리하여 얻은 조추출물뿐만 아니라 총백 추출물의 가공물도 포함한다. 예를 들어, 총백 추출물은 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.The term 'extract' as used herein to refer to the total bag includes not only the crude extract obtained by treating the extraction solvent on the total bag, but also the processed product of the total bag extract. For example, the total bag extract may be prepared in powder form by additional processes such as distillation under reduced pressure and freeze drying or spray drying.
또한, 본 발명의 총백 추출물은 광의로는 총백 자체를 동물에게 투여할 수 있도록 제형화된 총백 가공물, 예컨대, 총백 분말도 포함하는 의미를 갖는다. 비록 본 발명에서 총백 추출물로 실험을 진행하긴 하였으나, 총백 가공물과 같은 형태로도 목적하는 효과를 달성할 수 있음은 당업자라면 예상가능할 것이다.In addition, the total bag extract of the present invention has a meaning broadly also includes a total bag processed material, such as a total bag powder, formulated to administer the total bag itself to an animal. Although the experiment with the ginseng extract in the present invention, it will be expected to those skilled in the art that the desired effect can be achieved in the same form as the ginseng processed material.
한편, 본 명세서에서 용어 ‘유효성분으로 포함하는’이란 총백 추출물의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 본 발명의 한 구체예에서, 본 발명의 조성물 내에서 총백 추출물은 예를 들어, 0.001 mg/kg 이상, 바람직하게는 0.1 mg/kg 이상, 보다 바람직하게는 10 mg/kg 이상, 보다 더 바람직하게는 100 mg/kg 이상, 보다 더욱 더 바람직하게는 250 mg/kg 이상, 가장 바람직하게는 1 g/kg 이상 포함된다. 총백 추출물은 천연물로서 과량 투여하여도 인체에 부작용이 없으므로 본 발명의 조성물 내에 포함되는 총백 추출물의 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.
On the other hand, the term 'comprising as an active ingredient' as used herein means containing an amount sufficient to achieve the efficacy or activity of the total back extract. In one embodiment of the invention, the total bag extract in the composition of the invention is for example at least 0.001 mg / kg, preferably at least 0.1 mg / kg, more preferably at least 10 mg / kg, even more preferably Is at least 100 mg / kg, even more preferably at least 250 mg / kg, most preferably at least 1 g / kg. Since the total bag extract has no side effects on the human body even when the dose is excessively administered as a natural product, the upper limit of the total amount of the total bag extract included in the composition of the present invention may be carried out by those skilled in the art.
본 발명의 약학 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 may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, wherein the adjuvant includes excipients, disintegrants, sweeteners, binders, coatings, swelling agents, lubricants, lubricants Agents or flavoring agents may be used.
상기 약학 조성물은 투여를 위해서 상기 기재한 유효 성분 이외에 추가로 약제학적으로 허용 가능한 담체를 1종 이상 포함하여 약학 조성물로 바람직하게 제제화할 수 있다. The pharmaceutical composition may be preferably formulated into a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers in addition to the active ingredient described above for administration.
상기 약학 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. Formulation forms of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, nontoxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders include, but are not limited to, natural and synthetic gums such as starch, gelatin, glucose or beta-lactose, corn sweeteners, acacia, trackercance 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 in compositions formulated as liquid solutions are sterile and biocompatible, which include saline, sterile water, Ringer's solution, buffered saline, albumin injectable solutions, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers and bacteriostatic agents may be added as necessary. Diluents, dispersants, surfactants, binders and lubricants may also be added in addition to formulate into injectable formulations, 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 제제화 할 수 있다. Furthermore, the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA can be formulated according to each disease or component according to the appropriate method in the art.
본 발명의 약학 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 may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, or the like, and preferably, oral administration.
본 발명의 약학 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 약학 조성물의 1일 투여량은 0.001-10g/㎏이다.Suitable dosages of the pharmaceutical compositions of the invention vary depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, condition of food, time of administration, route of administration, rate of excretion and response to reaction, and usually The skilled practitioner can readily determine and prescribe a dosage effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dose of the pharmaceutical composition of the present invention is 0.001-10 g / kg.
본 발명의 약학 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화 함으로써 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 compositions of the present invention may be prepared in unit dosage form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Or by incorporating into a multi-dose container. In this case, the formulation may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, or may be in the form of extracts, powders, granules, tablets or capsules, and may further include a dispersant or stabilizer.
본 발명은 또한 총백 추출물을 유효성분으로 포함하는 뼈 성장 촉진용 식품 조성물을 제공한다.The present invention also provides a food composition for promoting bone growth comprising a total back extract as an active ingredient.
본 발명에 따른 식품 조성물은 상기 약학 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 may be formulated in the same manner as the pharmaceutical composition, 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, confectionery, diet bars, dairy products, meat, chocolates, pizzas, ramen noodles, other noodles, gums, ice creams, vitamin complexes, and health supplements. Etc.
본 발명의 식품 조성물은 유효성분으로서 총백 추출물 또는 총백 분말뿐만 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 총백 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 include not only ginseng extract or ginseng powder as an active ingredient, but also components commonly added during food production, and include, for example, proteins, carbohydrates, fats, nutrients, seasonings, and flavoring agents. Include. Examples of the above carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As the flavoring agent, natural flavoring agents (tauumatin, stevia extract (for example rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared with a drink and a beverage, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts may be further included in addition to the extract of the present invention.
본 발명은 상기 총백 추출물을 유효성분으로 포함하는 뼈 성장 촉진용 식품 조성물을 포함하는 건강기능식품을 제공한다. 건강기능식품이란, 총백 추출물 또는 총백 분말을 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 총백 추출물 또는 총백 분말의 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 promoting bone growth comprising the extract as an active ingredient. Health functional food is a food made by adding baekbaek extract or baekbaek powder to food materials such as beverages, teas, spices, gums, confectionery, encapsulated, powdered, suspension, etc. Means to bring, unlike the general medicine has the advantage that there is no side effect that can occur when taking a long-term use of the drug as a raw material. The health functional food of the present invention thus obtained is very useful because it can be consumed on a daily basis. The amount of the total bag extract or the total bag powder added in such a health functional food cannot be defined uniformly depending on the type of the health functional food, but it may be added within a range that does not impair the original taste of the food. It is usually in the range of 0.01 to 50% by weight, preferably 0.1 to 20% by weight. In addition, in the case of a health functional food in the form of pills, granules, tablets or capsules, it is usually added in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the dietary supplement of the present invention may be in the form of pills, tablets, capsules or beverages.
본 발명은 또한 뼈 성장 촉진용 의약 또는 식품의 제조를 위한 총백 추출물의 용도를 제공한다. 상기한 바와 같이 총백 추출물 또는 총백 분말은 뼈 성장 촉진 용도로 이용될 수 있다.The present invention also provides the use of a total bag extract for the manufacture of a medicament or food for promoting bone growth. As described above, the total back extract or total back powder may be used for promoting bone growth.
또한 본 발명은 포유동물에게 유효량의 총백 추출물을 투여하는 것을 포함하는 뼈 성장 촉진 방법을 제공한다.The present invention also provides a method for promoting bone growth, comprising administering to a mammal an effective amount of total back extract.
여기에서 사용된 용어 "포유동물"은 치료, 관찰 또는 실험의 대상인 포유동물을 말하며, 바람직하게는 인간을 말한다. As used herein, the term "mammal" refers to a mammal that is the subject of treatment, observation or experimentation, preferably 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 것임은 당업자에게 자명하다. 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.As used herein, the term “effective amount” means the amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human, as thought by a researcher, veterinarian, doctor or other clinician, Amounts that induce alleviation of the symptoms of the disease or disorder. It will be apparent to those skilled in the art that the effective amount and frequency of administration for the active ingredients of the present invention will vary depending on the desired effect. Therefore, the optimum dosage to be administered can be readily determined by one skilled in the art and includes the type of disease, the severity of the disease, the amount of active ingredients and other ingredients contained in the composition, the type of formulation, and the age, weight, general health of the patient. It may be adjusted according to various factors, including the condition, sex and diet, time of administration, route of administration and rate of composition, duration of treatment, and drugs used simultaneously.
본 발명의 치료방법에서 총백 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 treatment method of the present invention, the composition comprising the extract of baekbaek as an active ingredient is administered in a conventional manner through oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, intraocular or intradermal routes. May be administered.
본 발명의 이점 및 특징, 그리고 그것들을 달성하는 방법은 상세하게 후술되어 있는 실시예들을 참조하면 명확해질 것이다. 그러나 본 발명은 이하에서 개시되는 실시예들에 한정되는 것이 아니라 서로 다른 다양한 형태로 구현될 것이며, 단지 본 실시예들은 본 발명의 개시가 완전하도록 하고, 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에게 발명의 범주를 완전하게 알려주기 위해 제공되는 것이며, 본 발명은 청구항의 범주에 의해 정의될 뿐이다.
Advantages and features of the present invention and methods for achieving them will be apparent with reference to the embodiments described below in detail. However, the present invention is not limited to the embodiments disclosed below, but will be implemented in various forms, and only the embodiments are intended to complete the disclosure of the present invention, and the general knowledge in the technical field to which the present invention pertains. It is provided to fully convey the scope of the invention to those skilled in the art, and the present invention is defined only by the scope of the claims.
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.
Hereinafter, preferred examples are provided to help the understanding of the present invention, but the following examples are merely for exemplifying the present invention, and various changes and modifications within the scope and spirit of the present invention are apparent to those skilled in the art. It is natural that such variations and modifications fall within the scope of the appended claims.
[[ 실시예Example : : 총백Total back 추출물 제조] Extract manufacture]
제조예Production Example 1: One: 총백Total back 추출물의 제조 Preparation of Extract
총백 200 g을 10배의 70% 에탄올로 1시간씩 3회에 걸쳐 환류 냉각 추출한 후 여과한 액을 감압농축기를 이용해 농축한 다음 동결건조하여 총백 추출물을 제조하였다.
200 g of the total bag was refluxed and extracted three times for 1 hour with 10-fold 70% ethanol, and the filtrate was concentrated using a vacuum condenser and then lyophilized to prepare a total bag extract.
[[ 실험예Experimental Example : 생체 외 실험]: In vitro experiment]
실험예Experimental Example 1: 조골세포 1: osteoblast MG63MG63 cellcell 의 of MTTMTT 분석에 의한 세포 독성검사Cytotoxicity test by analysis
96 well plate에 MG63 세포를 10% FBS, 100 unit/㎖ 페니실린(penicillin), 100 ㎎/㎖ 스트렙토마이신(streptomycin) 등을 포함시킨 DMEM 배양액을 사용하였고, 37℃, 5% CO2배양기에서 배양하였다. 세포가 각 well에 70%이상 찼을 때 배양액을 제거하고 대조군과 처리군으로 각각 구분하여 동일조건에서 배양하였다. 처리군은 배양된 조골세포에 배양된 MG63 세포에 1 ㎍/mL와 5 ㎍/mL로 총백 추출물을 처리하고, 1시간 후에 100 ㎍/mL 팔미테이트(palmitate)를 처리하여 세포 독성을 유발하고, 24시간 후에 3-(4,5-dimethythiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) 용액을 10 ㎕를 대조군과 총백 처리군에 첨가한 후 4시간 동안 CO2배양기에서 배양하였다. 반응액을 제거하고 100 ㎕의 dimethyl sulfozide (DMSO)를 첨가하여 세포 내에 형성된 formazan결정을 용해시킨 후, 총백 추출물을 처리하지 않은 MG63 세포의 대조군, 1 ㎍/mL 총백 처리군, 및 5 ㎍/mL 총백 처리군을 준비하였다.MG63 cells were used in a 96 well plate using a DMEM medium containing 10% FBS, 100 unit / ml penicillin, 100 mg / ml streptomycin, and the like incubated in a 37 ° C., 5% CO 2 incubator. . When the cells were more than 70% filled in each well, the culture medium was removed and divided into control and treatment groups, respectively, and cultured under the same conditions. Treatment group was treated with total bag extract at 1 μg / mL and 5 μg / mL to MG63 cells cultured in cultured osteoblasts, and then treated with 100 μg / mL palmitate after 1 hour to induce cytotoxicity, After 24 hours, 10 μl of 3- (4,5-dimethythiazol-2yl) -2,5-diphenyl tetrazolium bromide (MTT) solution was added to the control and total bag treatment groups, and then cultured in a CO 2 incubator for 4 hours. The reaction solution was removed and 100 μl of dimethyl sulfozide (DMSO) was added to dissolve the formazan crystals formed in the cells. A total back treatment group was prepared.
ELISA reader를 이용하여 570 ㎚ 파장에서 흡광도를 측정함으로써 대조군, 1 ㎍/mL 총백 처리군, 및 5 ㎍/mL 총백 처리군의 세포 생존율을 측정하고 그 결과를 도 1에 나타내었다.By measuring the absorbance at 570 nm wavelength using an ELISA reader, the cell viability of the control group, 1 μg / mL total bag treatment group, and 5 μg / mL total bag treatment group was measured and the results are shown in FIG. 1.
총백 추출물은 팔미테이트에 의한 세포 독성을 억제하고 농도 의존적으로 세포사멸을 억제하고 세포의 생존을 높였으며, 고농도 총백 추출물은 대조군에 비해 세포 생존을 향상시켰다. Chongbaek extract inhibited cytotoxicity by palmitate, inhibited apoptosis and increased cell survival in a concentration-dependent manner, and high concentration Chongbaek extract improved cell viability compared to the control group.
각 군 간 통계학적 유의성은 prism softward version7.0(Graphpad software inc., San Diego, CA, USA)을 이용하여 one way ANOVA와 T-test로 분석하였으며, 이하 실험예에서도 동일한 방법으로 분석하였다.
Statistical significance between groups was analyzed by one way ANOVA and T-test using prism softward version 7.0 (Graphpad software inc., San Diego, Calif., USA).
실험예Experimental Example 2: 2: MG63MG63 세포의 Cellular ALPALP 활성도 측정 Activity measurement
실험예 1과 동일하게 배양된 MG63 세포를 준비하고, ALP (alkaline phosphatase) 활성도 측정은 아래와 같은 방법으로 수행하였다.MG63 cells cultured in the same manner as in Experimental Example 1 were prepared, and ALP (alkaline phosphatase) activity was measured in the following manner.
MG63 세포는 96 well plate에 분주하고, 무처리된 대조군과 제조예 1의 총백 추출물 처리군으로 구분하여 CO2배양기에서 배양하였다. 이때, 처리군에서는 시료에 제조예 1의 총백 추출물을 1㎍/㎖, 및 5㎍/㎖ 농도로 각각 처리하였다. 4일 후 배양된 세포의 상청액(supernatant)을 수집한 후 Abcam (ab83369)의 키트를 사용하여 ALP 활성도를 405 ㎚ 파장에서 측정하였다. standard의 흡광도를 이용하여 단백질 농도와 흡광도의 관계식을 작성하고 이를 적용하여 각 처리군별 세포액의 단백질 농도를 계산하였다. ALP농도를 단백질 농도로 나누어 아래와 같은 관계식에 적용하여 ALP 활성도를 계산하여 그 결과를 도 2에 나타내었다.MG63 cells were dispensed into 96 well plates, and divided into untreated controls and total bag extract treatment groups of Preparation Example 1 and cultured in a CO 2 incubator. At this time, in the treatment group, the total bag extract of Preparation Example 1 was treated at 1 µg / ml and 5 µg / ml concentrations, respectively. Four days later, supernatants of cultured cells were collected and ALP activity was measured at 405 nm using a kit of Abcam (ab83369). Using the absorbance of the standard, the relationship between protein concentration and absorbance was prepared and applied to calculate the protein concentration of the cell solution for each treatment group. The ALP concentration was divided by the protein concentration and applied to the following relationship to calculate the ALP activity and the results are shown in FIG. 2.
[식][expression]
ALP는 세포가 파괴 정도를 나타내지만 세포 실험에서는 조골세포가 파괴되어야 새로운 세포가 생성되므로 ALP활성이 증가하는 것이 세포 성장이 높아지는 것인데 5㎍/㎖ 총백 처리군에서 ALP 활성을 높였으므로 이들이 세포 분열을 향상시키는 것으로 판단된다.
ALP shows the degree of cell destruction, but in cell experiments, osteoblasts are destroyed before new cells are produced, so increasing ALP activity increases cell growth. It seems to improve.
실험예Experimental Example 3: 3: TGFTGF -β 신호전달 관련 유전자의 of -β signaling related genes mRNAmRNA 발현 분석 Expression analysis
실험예 1과 동일한 조건으로 처리한 GM63세포의 대조군, 1 ㎍/mL 총백 처리군, 및 5 ㎍/mL 총백 처리군에서의 TGF-β 신호전달 관련 유전자의 mRNA 발현 분석 결과를 도 3 및 도 4에 나타내었다.The results of mRNA expression analysis of TGF-β signaling-related genes in the control group, 1 μg / mL total bag treatment group, and 5 μg / mL total bag treatment group of GM63 cells treated under the same conditions as in Experimental Example 1 are shown in FIGS. 3 and 4. Shown in
골세포 성장에 관여하는 신호전달에는 여러 가지가 있지만 특정한 호르몬을 처리하지 않을 때는 transforming growth factor-β(TGF-β와 wnt 신호전달이 활성화될 때 골세포 성장이 증가하게 된다. 이중이 TGF-β 신호전달에 관여하는 유전자의 mRNA 발현을 측정하였다. TGF-β 신호전달은 BMP-2 -> pSMAD1/5/7 -> SMAD4 -> 뼈 성장으로 이어진다.There are several signaling pathways involved in bone cell growth, but when certain hormones are not treated, bone cell growth increases when transforming growth factor-β (TGF-β and wnt signaling are activated. MRNA expression of genes involved in signaling was measured TGF-β signaling leads to BMP-2-> pSMAD1 / 5/7-> SMAD4-> bone growth.
본 연구에서는 고농도의 총백이 BMP-2의 발현을 증가시키므로 TGF-β 신호전달을 향상시킬 가능성이 높다. 또한 TGF-β에서 총백은 농도 의존적으로 pSMAD1/5/7의 결과 증가하는 SMAD4의 발현을 향상시켰다. 그러므로 총백 추출물은 TGF-β 수용체의 신호전달을 향상시키고 이것이 골의 세포 분열을 향상시킬 수 있을 것으로 사료된다.
In this study, high concentrations of BBC-2 increase the expression of BMP-2, which is likely to improve TGF-β signaling. Total back in TGF-β also enhanced the expression of SMAD4, resulting in a concentration-dependent increase in pSMAD1 / 5/7. Therefore, the baekbaek extract may enhance the signaling of TGF-β receptor, which may improve bone cell division.
실험예Experimental Example 4: 4: wntwnt 신호전달 관련 유전자의 Signaling related genes mRNAmRNA 발현 분석 Expression analysis
실험예 1과 동일한 조건으로 처리한 GM63세포의 대조군, 1 ㎍/mL 총백 처리군, 및 5 ㎍/mL 총백 처리군에서의 wnt 신호전달 관련 유전자의 mRNA 발현 분석 결과를 도 5 및 도 6에 나타내었다.Results of mRNA expression analysis of wnt signaling-related genes in the control group, 1 μg / mL total bag treatment group, and 5 μg / mL total bag treatment group of GM63 cells treated under the same conditions as in Experimental Example 1 are shown in FIGS. 5 and 6. It was.
wnt 신호전달에 관여하는 LRP가 활성화되면 β-catenin이 인산화되지 않고 세포질에서 핵으로 이동하여 wnt target 유전자의 발현을 증가시켜 wnt 신호전달이 증가하게 되므로 LRP5와 β-catenin의 mRNA 발현을 조사하였다. 특히 고농도 총백 추출물이 LRP5와 β-catenin mRNA 발현을 대조군에 비해 현저하게 증가시킨 것으로 나타났다. 따라서 총백 추출물은 조골세포에서 TGF-β와 wnt 신호전달을 통해 세포 성장을 증가시키는 것으로 사료된다.
When LRP involved in wnt signaling was activated, β-catenin was not phosphorylated and moved from the cytoplasm to the nucleus to increase the expression of wnt target genes, thereby increasing wnt signaling. In particular, high concentration extracts significantly increased LRP5 and β-catenin mRNA expression compared to the control group. Therefore, baekbaek extract is thought to increase cell growth through TGF-β and wnt signaling in osteoblasts.
[[ 실시예Example : : 총백Total back 추출물 투여] Extract administration]
실시예Example 1 One
4주령 성장기 수컷 백서에게 AIN-93G 사료에서 지방 함량만 43열량%로 조정한 사료와 함께 제조예 1에 따라 제조된 총백 추출물을 경구로 0.015% 식이를 4주간 제공하였다. Four-week-old male rats were orally given 0.015% diet for 4 weeks orally with a total white extract prepared according to Preparation Example 1 together with a diet adjusted to only 43 calories percent fat in AIN-93G feed.
실시예Example 2 2
총백 추출물을 0.015% 식이를 제공하지 않고, 0.045% 식이로 제공한 것을 제외하고는 실시예 1과 동일한 방법으로 식이를 제공하였다.The diet was provided in the same manner as in Example 1 except that the total back extract was provided in a 0.045% diet without providing a 0.015% diet.
음성 대조군Negative control
총백 추출물을 제공하지 않은 것을 제외하고는 실시예 1과 동일한 방법으로 식이를 제공하였다.A diet was provided in the same manner as in Example 1 except that the extract of Chongbaek was not provided.
양성 대조군Positive control
총백 추출물 대신에 20㎍/kg체중(유트로핀_엘지생명과학)을 피하 주사 투여한 것을 제외하고는 실시예 1과 동일한 방법으로 식이를 제공하였다.
The diet was provided in the same manner as in Example 1, except that 20 µg / kg body weight (Eutropin_Llife Science) was administered subcutaneously instead of the total back extract.
[[ 실험예Experimental Example : 생체 내 시험]: In vivo testing]
실험예Experimental Example 5: 식이 공급 후 체중 측정 5: weight measurement after dietary feeding
도 7은 4주 동안 수컷 백서에게 AIN-93G 사료에서 지방 함량만 43열량%로 조정한 사료를 공급한 후 체중을 측정하여 비교한 그래프이다.FIG. 7 is a graph comparing body weights of four white rats after feeding with a diet adjusted to only 43 calories of fat in AIN-93G feed.
이에 따르면, 4주 동안 식이를 공급한 후 체중은 대조군과 총백 추출물 투여 군간의 통계적으로 유의한 차이는 없었다.
According to this, there was no statistically significant difference between the control group and the total back extract administration group after feeding the diet for 4 weeks.
실험예Experimental Example 6: 뼈 성장 효과 분석 6: bone growth effect analysis
백서의 정강뼈(tibia)와 넙다리뼈(femur)의 길이 성장을 관찰하여 그 결과를 아래의 도 8에 및 도 9에 나타내었다.The growth of the tibia and femur of the white paper was observed and the results are shown in FIGS. 8 and 9 below.
도 8에 따르면, 4주 동안 식이를 공급한 후 정강뼈(tibia)의 길이는 음성대조군(35.966mm)에 비해 양성대조군(36.704)에서 통계적으로 유의하게 증가하였고, 실시예 2는 37.833mm로 음성대조군보다 105.19% 길었으며, 양성대조군 보다 더 큰 값을 나타내었다.According to FIG. 8, after feeding for 4 weeks, the length of tibia was statistically significantly increased in the positive control group (36.704) compared to the negative control group (35.966 mm), and Example 2 was negative in 37.833 mm. It was 105.19% longer than the control group, and larger than the positive control group.
도 9에 따르면, 4주 동안 식이를 공급한 후에 넙다리뼈(femur) 길이는 양성대조군은 음성대조군과 통계적으로 유의한 차이를 보이지 않았으나 300 mg/kg(체중)으로 식이 제공한 실시예 2에서는 음성대조군에 비해 통계적으로 유의하게 길어진 것을 관찰할 수 있었다.
According to Figure 9, after feeding the diet for 4 weeks femur length (positive control group) did not show a statistically significant difference from the negative control group, but in Example 2 diet was provided at 300 mg / kg (weight) Significantly longer than the negative control group was observed.
실험예Experimental Example 7: 성장판의 H-E 염색 7: H-E staining of growth plate
백서의 관절 부위에 있는 성장판을 H-E로 염색한 현미경 이미지를 도 10에 나타내었고, 성장판에서 증식부와 비대부의 길이를 비교한 그래프를 도 11 및 도 12에 나타내었으며, 관절 전체 길이를 비교한 그래프를 도 13에 나타내었다.10 shows a microscopic image of HE staining of the growth plate on the joint area of the white paper, and graphs comparing the lengths of the proliferation part and the hypertrophy part of the growth plate are shown in FIGS. 11 and 12. The graph is shown in FIG.
이에 다르면, 세포핵(nucleus)이 일정하게 증가하는지를 살펴 보았는데 음성대조군은 성장판 부위가 좁고 셀들이 불규칙적으로 나열되어 있는 것을 볼 수 있었으며, 양성 대조군은 성장판 부위가 넓고 세포의 핵들이 규칙적으로 나열 되어 있는 것을 볼 수 있었다. In other cases, we examined whether the nucleus increased regularly, but the negative control group showed a narrow growth plate area and irregularly arranged cells. Could see.
실시예 1과 2는 음성대조군에 비해서는 농도 의존적으로 성장판 부위가 넓어지고 세포도 규칙적으로 나열된 것을 확인할 수 있었다.
In Examples 1 and 2, the growth plate region was widened in a concentration-dependent manner and the cells were regularly arranged as compared to the negative control group.
실험예Experimental Example 8: 골밀도 변화 관찰 8: Observe Bone Density Change
4주 후의 요추(Lumbar spine)의 골밀도 (bone mineral density; BMD)와 넙다리뼈(femur)의 골밀도를 측정하여 도 14 및 도 15에 각각 나타내었다.After 4 weeks, bone mineral density (BMD) of the lumbar spine and bone density of femur were measured and shown in FIGS. 14 and 15, respectively.
도 14에 따르면, 4주 동안 요추(Lumbar spine)의 골밀도 (bone mineral density; BMD)의 증가량은 실시예 2가 음성대조군에 비해 많았으며, 도 15에 따르면, 넙다리뼈(femur)의 BMD의 증가량도 실시예 2가 음성대조군에 비해 많았으며 양성대조군도 음성대조군에 비하여 넙다리뼈의 골밀도를 증가시켰다.
According to Figure 14, the increase in bone mineral density (BMD) of the lumbar spine (Lumbar spine) for 4 weeks, compared to the negative control group in Example 2, according to Figure 15, the BMD of femur Example 2 was more increased than the negative control group, and the positive control group also increased bone density of the femur compared to the negative control group.
실험예Experimental Example 9: 혈청 내 9: in serum ALPALP 농도 density
백서를 해부하여 혈청 내 ALP 농도를 측정한 결과를 도 16에 나타내었고, 혈청내 오스테오칼신(osteocalcin)의 농도를 도 17에 나타내었다.The results of dissecting the white paper and measuring the serum ALP concentration are shown in FIG. 16, and the concentration of osteocalcin in the serum is shown in FIG. 17.
이에 따르면, 뼈의 분해 정도를 나타내는 ALP 농도는 음성대조군에 비해 실시예 2에서 낮게 나타났고, 양성대조군과 유사한 값을 나타내었다.According to this, the ALP concentration representing the degree of bone degradation was lower in Example 2 than in the negative control group, and showed a similar value to the positive control group.
또한, 뼈의 합성 정도를 알 수 있는 지표인 혈청 내 오스테오칼신(osteocalcin)의 농도는 음성대조군에 비해 실시예 2에서 높게 나타났으며 양성대조군과 통계적인 차이가 없었다.In addition, the concentration of osteocalcin in serum, which is an indicator of the degree of bone synthesis, was higher in Example 2 than in the negative control group and was not statistically different from the positive control group.
결과적으로 넙다리뼈(femur), 정강뼈(tibia)의 길이가 음성대조군에 비해 실시예 2에서 더 긴 것과 혈청 내 오스테오칼신 농도와 양의 상관 관계를 나타낸다.
As a result, the length of femur and tibia is longer in Example 2 than in the negative control group and shows positive correlation with serum osteocalcin concentration.
이상, 본 발명의 실시예들에 대하여 설명하였으나, 해당 기술 분야에서 통상의 지식을 가진 자라면 특허청구범위에 기재된 본 발명의 사상으로부터 벗어나지 않는 범위 내에서, 구성 요소의 부가, 변경, 삭제 또는 추가 등에 의해 본 발명을 다양하게 수정 및 변경시킬 수 있을 것이며, 이 또한 본 발명의 권리범위 내에 포함된다고 할 것이다.
As described above, embodiments of the present invention have been described, but those skilled in the art may add, change, delete, or add elements within the scope not departing from the spirit of the present invention described in the claims. The present invention may be modified and changed in various ways, etc., which will also be included within the scope of the present invention.
Claims (14)
상기 총백 추출물은 물, 탄소수 1-4의 알코올, 또는 이들의 혼합용매에 의해 추출된 것을 특징으로 하는 성장판 확장 및 골길이 성장 촉진용 약학 조성물.The method of claim 1,
The total back extract is a growth plate expansion and bone growth growth pharmaceutical composition, characterized in that extracted by water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
상기 성장판 확장 및 골길이 성장 촉진용 약학 조성물은 TGF-β(Transforming growth factor beta) 수용체 및 wnt 수용체 중에서 선택된 1종 이상의 신호전달을 향상시켜 뼈 성장을 유도하는 것을 특징으로 하는 성장판 확장 및 골길이 성장 촉진용 약학 조성물.The method of claim 1,
The growth plate expansion and bone length growth promoting pharmaceutical composition is characterized in that the growth plate expansion and bone length growth characterized in that inducing bone growth by enhancing one or more signaling selected from TGF-β (Transforming growth factor beta) receptor and wnt receptor Promotional pharmaceutical composition.
상기 성장판 확장 및 골길이 성장 촉진용 약학 조성물은 성장기 어린이 또는 청소년의 성장판 확장 및 골길이 성장 촉진용인 것을 특징으로 하는 성장판 확장 및 골길이 성장 촉진용 약학 조성물.The method of claim 1,
The growth plate expansion and bone length growth promoting pharmaceutical composition is growth plate expansion and bone length growth promoting pharmaceutical composition, characterized in that for growth plate expansion and bone length growth promoting of children or adolescents.
상기 성장판 확장 및 골길이 성장 촉진용 약학 조성물은 비만인 성장기 어린이 또는 청소년의 성장판 확장 및 골길이 성장 촉진용인 것을 특징으로 하는 성장판 확장 및 골길이 성장 촉진용 약학 조성물.The method of claim 4, wherein
The growth plate expansion and bone length growth promoting pharmaceutical composition is growth plate expansion and bone length growth promoting pharmaceutical composition, characterized in that for growth plate expansion and bone length growth promotion of obese growth phase children or adolescents.
상기 총백 추출물은 물, 탄소수 1-4의 알코올, 또는 이들의 혼합용매에 의해 추출된 것을 특징으로 하는 성장판 확장 및 골길이 성장 촉진용 식품 조성물.The method of claim 6,
The total back extract is a food composition for growth plate expansion and bone length growth, characterized in that extracted by water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
상기 성장판 확장 및 골길이 성장 촉진용 식품 조성물은 TGF-β(Transforming growth factor beta) 수용체 및 wnt 수용체 중에서 선택된 1종 이상의 신호전달을 향상시켜 뼈 성장을 유도하는 것을 특징으로 하는 성장판 확장 및 골길이 성장 촉진용 식품 조성물.The method of claim 6,
The growth plate expansion and bone length growth promoting food composition is characterized in that the growth plate expansion and bone length growth characterized in that inducing bone growth by enhancing one or more signaling selected from TGF-β (Transforming growth factor beta) receptor and wnt receptor Promotional food composition.
상기 성장판 확장 및 골길이 성장 촉진용 조성물은 성장기 어린이 또는 청소년의 성장판 확장 및 골길이 성장 촉진용인 것을 특징으로 하는 성장판 확장 및 골길이 성장 촉진용 식품 조성물.The method of claim 6,
The growth plate expansion and bone length growth promoting composition is growth plate expansion and bone length growth promoting food composition, characterized in that for growth plate expansion and bone length growth promotion of children or adolescents.
상기 성장판 확장 및 골길이 성장 촉진용 식품 조성물은 비만인 성장기 어린이 또는 청소년의 성장판 확장 및 골길이 성장 촉진용인 것을 특징으로 하는 성장판 확장 및 골길이 성장 촉진용 식품 조성물.The method of claim 6,
The growth plate expansion and bone length growth promoting food composition is growth plate expansion and bone length growth promoting food composition, characterized in that for growth plate expansion and bone length growth promotion of obese growth phase children or adolescents.
상기 단계 이후 감압 농축하는 단계를 추가로 수행하는 것을 특징으로 하는 성장판 확장 및 골길이 성장 촉진용 약학 조성물의 제조방법.The method of claim 11,
Method for preparing a growth plate expansion and bone length growth promoting pharmaceutical composition, characterized in that for further performing the step of concentration under reduced pressure after the step.
상기 단계 이후 감압 농축하는 단계를 추가로 수행하는 것을 특징으로 하는 성장판 확장 및 골길이 성장 촉진용 식품 조성물의 제조방법.The method of claim 13,
Method for producing a growth plate expansion and bone length growth promoting food composition, characterized in that for further performing the step of concentration under reduced pressure after the step.
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| PCT/KR2019/005037 WO2019209061A1 (en) | 2018-04-26 | 2019-04-26 | Bone growth-promoting composition comprising allium fistulosum linn as active ingredient |
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| JP2001524119A (en) | 1997-05-06 | 2001-11-27 | ミユールバウアー，ローマン・コンラツド | Botanical extract for the treatment of increased bone resorption |
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| KR101313284B1 (en) * | 2010-10-28 | 2013-09-30 | 한국 한의학 연구원 | Composition for the prevention and treatment of lipid related cardiovascular disease or obesity containing the extracts of Allium fistulosum L as active ingredient |
| KR101483255B1 (en) | 2012-05-01 | 2015-01-15 | 재단법인 전남생물산업진흥원 | Korean Herb Tea composing of extract from Spring onion root and Method preparing thereof |
| KR101642176B1 (en) * | 2014-01-10 | 2016-07-22 | 주식회사 설악바이오 | Composition for enhancing growth and reinforcing immunity |
| KR101637344B1 (en) * | 2014-11-14 | 2016-07-08 | 중앙대학교 산학협력단 | Composition for stimulating bone growth comprising extract of Allium hookeri root |
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| JP2001524119A (en) | 1997-05-06 | 2001-11-27 | ミユールバウアー，ローマン・コンラツド | Botanical extract for the treatment of increased bone resorption |
| US20060039998A1 (en) * | 2002-10-01 | 2006-02-23 | Hiromu Ohnogi | Remedies |
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