KR20060026938A - Pharmacuetical compositions comprising eleutheroside e having bone growth-promoting effects - Google Patents

Pharmacuetical compositions comprising eleutheroside e having bone growth-promoting effects Download PDF

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KR20060026938A
KR20060026938A KR1020060020790A KR20060020790A KR20060026938A KR 20060026938 A KR20060026938 A KR 20060026938A KR 1020060020790 A KR1020060020790 A KR 1020060020790A KR 20060020790 A KR20060020790 A KR 20060020790A KR 20060026938 A KR20060026938 A KR 20060026938A
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임강현
김영호
김호철
부영민
박선영
김명규
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김영호
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Abstract

본 발명은 골다공증을 비롯한 각종 골질환의 예방 및 치료에 유효한 골강화 조성물 및 이를 함유하는 음식품, 의약품 또는 사료를 제공하는 것으로, 일상적으로 계속 섭취가 가능하고 안전하고 값이 싼 골강화 조성물을 제공하고자 한다.The present invention is to provide a bone strengthening composition effective for the prevention and treatment of various bone diseases, including osteoporosis and food and beverages, medicines or feed containing the same, to provide a bone strengthening composition that can be routinely ingested and safe and inexpensive I would like to.

본 발명의 엘루테로사이드(eleutheroside) E는 흰털오가피에서 분리한 성분으로 골아세포증식촉진활성, 골성장촉진 및 골강화작용 효과를 확인할 수 있으며 이는 성장장애의 예방 및 치료제, 골강화 보조제 및 골강화식품 등으로서 사용할 수 있다.Elutheheroside E of the present invention can be identified as a component isolated from the white hairy organ, osteoblast proliferation promoting activity, bone growth promotion and bone mineralization effect, which prevents and treats growth disorders, bone mineralization adjuvant and bone mineralization It can be used as food.

본 발명은 골아세포증식촉진활성, 골성장촉진 및 골강화작용 효과를 갖는 엘루테로사이드(eleutheroside) E를 함유한 골강화조성물과 이를 함유한 음식품, 의약품 또는 사료를 제공한다. The present invention provides a bone mineralization composition containing elutheroside E having osteoblast proliferation promoting activity, bone growth promoting effect and bone mineralization effect and food and beverage, medicine or feed containing the same.

엘루테로사이드(eleutheroside) E, 골아세포, 골성장, 골강화 Elutheroside E, osteoblasts, bone growth, bone mineralization

Description

골성장 촉진활성을 갖는 엘루테로사이드 E를 함유하는 약학조성물{Pharmacuetical compositions comprising Eleutheroside E having bone growth-promoting effects}Pharmacuetical compositions comprising Eleutheroside E having bone growth-promoting effects

도 1은 통상군과 엘루테로사이드(eleutheroside) E를 래트(Rat)에게 투여하였을 때, 각 사료섭취군에 관하여 경골의 성장률을 비교한 그래프이다.1 is a graph comparing the growth rate of the tibia with respect to each feed intake group, when the normal group and eleutheroside E are administered to rats.

본 발명은, 골 성장 및 골 강화 작용을 갖는 엘루테로사이드(eleutheroside) E에 관한 것이다. 또한 본 엘루테로사이드(eleutheroside) E를 배합한 음식품, 의약품, 또는 사료에 관한 것이다. 본 발명의 엘루테로사이드(eleutheroside) E는 골아세포를 증식시키고 골성장 촉진 효능이 있어서, 골 대사 균형이 깨져서 발생하는 골질환의 예방이나 치료, 또한 초등학생 등 젊은 층에 있어 성장기의 골강화 및 성장에 유용하다.The present invention relates to elutheroside E having bone growth and bone strengthening action. The present invention also relates to a food or beverage, a medicine, or a feed containing the eleutheroside E. Elutheheroside E of the present invention proliferates osteoblasts and has an effect of promoting bone growth, thus preventing or treating bone diseases caused by a breakdown of bone metabolic balance, and strengthening and growing bone during growth in young people such as elementary school students. Useful for

Figure 112006015734246-PAT00001
Figure 112006015734246-PAT00001

최근 골다공증의 증가와 더불어 젊은층의 골절률 증가 등 각종 골질환의 증가가 사회문제로 대두되고 있다. 골다공증 환자는 전국에 약 1,000만명이 있다고 추정되고 있고, 고령화가 진행됨에 따라 2010년에는 환자수가 1,600만명까지 증가한다는 예측이 있다. 골다공증은, 주로 폐경기 여성에 있어, 여성 호르몬(Estrogen hormone)의 감소의 영향으로부터 골 형성과 골 파괴가 균형이 깨지고 일어나는 질환이지만, 남성이라도 노령화에 수반하여 골질량의 감소가 보여지고, 현재 50세이상 연령층에 약 200만명의 골다공증 환자가 있다. 또, 최근 20년 동안 초중학생의 골절률은 2배 이상에 증가하고 있는 실정이다. 골다공증을 예방한다는 측면에서 보더라도 젊은 때부터 골질량을 높이고, 높은 최대 골량을 얻는 것은 상당히 중요하다. 이와 같이, 뼈의 건강을 유지하는 것은 성별이나 연령과 관계없이 전사회적인 관심사이다.Recently, as osteoporosis increases, the increase of various bone diseases such as an increase in fracture rate of young people is emerging as a social problem. It is estimated that there are about 10 million osteoporosis patients nationwide, and as the aging progresses, the number of patients is expected to increase to 16 million in 2010. Osteoporosis is a disease in which bone formation and bone destruction are out of balance due to the reduction of the female hormone (Estrogen hormone), mainly in postmenopausal women, but even men are seeing a decrease in bone mass with aging. There are about 2 million osteoporosis patients in this age group. In addition, the fracture rate of elementary and middle school students has more than doubled in recent 20 years. In terms of preventing osteoporosis, it is very important to increase bone mass and to obtain high maximum bone mass from a young age. As such, maintaining bone health is a global concern regardless of gender or age.

예전부터 골 질환의 예방 또는 치료방법으로서 식이 요법에 의한 칼슘 보급, 가벼운 운동, 일광욕 및 약물 치료 등이 행해지고 있다. 식이 요법에 의한 칼슘 보급에는 탄산칼슘, 인산칼슘 등의 칼슘염이나, 우골분(牛骨粉), 난각(卵殼), 어골분(魚骨粉) 등의 천연 칼슘 제제가 사용되고 있지만, 용해성이나 흡수성, 미각적인 점에서 경구 섭취에 적합한 제제라고는 할 수 없다. 적당한 운동은 골량을 늘리고, 뼈를 강화시키기 때문에 산책이나 워킹(walking)은 뼈를 건강하게 하지만, 몸이 약해지고 있는 경우는 가벼운 운동도 번거로운 것이며, 더구나 거동조차 힘든 노인은 거의 운동을 할 수 없다. 일광욕은 활성비타민 D3의 보급이라는 점에서는 좋지만 이것만으로는 불충분하다. 약물 투여에는 비스포스포네이트(bisphosphonate)나 칼시토닌(calcitonin)제제 등이 사용되며 골다공증의 치료에 유효하다고 알려져 있다. 하지만 이러한 물질은 전문의약품이고, 그 복용에는 특별한 주의가 필요하며, 이명, 두통, 식욕부진 등 부작용의 위험성도 있어 계속적인 식품 소재로서 사용 가능한 것이 아니다.Background Art In the past, as a method of preventing or treating bone diseases, calcium diffusion by diet, light exercise, sunbathing and drug treatment have been performed. Although calcium salts such as calcium carbonate and calcium phosphate, natural calcium preparations such as right bone meal, eggshell and fish bone meal are used for calcium diffusion by diet, solubility, water absorption, In terms of taste, it is not suitable for oral ingestion. Proper exercise increases bone mass and strengthens bones, so walking and walking make bones healthy, but when your body is weak, light exercise can be cumbersome, and hardly even older people can hardly exercise. Sunbathing is good in terms of the spread of active vitamin D3, but this is not enough. Bisphosphonate or calcitonin is used for drug administration and is known to be effective in the treatment of osteoporosis. However, these substances are specialty medicines, and they require special attention, and there is a risk of side effects such as tinnitus, headache, and anorexia, so they are not usable as a continuous food ingredient.

본 발명은 일상적으로 계속 섭취 가능한 골 강화제로서, 골 강화 작용을 가지며 안전하고 저가이면서 식품에 폭넓게 이용하는 것이 가능한 식품 소재를 제공하는 것을 목적으로 한다.It is an object of the present invention to provide a food material that is a bone strengthening agent that can be continuously ingested on a daily basis, which has a bone strengthening action, which is safe and inexpensive, and which can be widely used in food.

본 발명은, 엘루테로사이드(eleutheroside) E의 골성장 및 골강화 촉진에 대한 효과를 규명하는 생리활성에 관한 것이다. 본 발명에서는 엘루테로사이드(eleutheroside) E의 골 성장 효과를 약리학적으로 관찰하여, 골 성장제, 골 강화 제, 성장 장애 치료제 및 성장 강화 보조제로서 쓰일 수 있는 가능성을 제시하고자하는 목적으로 계획되었다.The present invention relates to a physiological activity that identifies the effect of elutheroside E on promoting bone growth and bone strengthening. In the present invention, by pharmacologically observing the bone growth effect of eluteroside (eleutheroside) E, it was intended to present the possibility of being used as a bone growth agent, bone enhancer, growth disorder treatment and growth enhancer.

이에, 본 발명자들은 엘루테로사이드(eleutheroside) E에 관하여 골성장 및 골강화 촉진 효능 탐색을 행하여 골아세포 증식 및 석회화 촉진 활성을 통한 골 성장 촉진 및 골 대사의 개선을 발견하여 본 발명을 완성하였다.Accordingly, the present inventors have completed the present invention by discovering an improvement in bone growth and bone mineralization promoting effect on elutheroside E and promoting bone growth and bone metabolism through osteoblast proliferation and calcification promoting activity.

즉, 청구항 1에 기재된 발명(이하 "발명 1"로 명명함.)의 골 강화 조성물은 골아세포 증식 촉진 활성, 골성장 및 골강화 작용을 갖는 엘루테로사이드(eleutheroside) E를 유효 성분으로서 함유한 것을 특징으로 한다.That is, the bone-enhancing composition of the invention described in claim 1 (hereinafter referred to as "Invention 1") contains elutheroside E having osteoblast proliferation promoting activity, bone growth, and osteoporosis as an active ingredient. It is characterized by.

또한, 본 발명의 음식품, 의약 또는 사료는, 본 발명 1의 엘루테로사이드(eleutheroside) E를 배합하여 사용된 것이 바람직하다.In addition, it is preferable that the food-drinks, medicine, or feed of this invention mix | blended and use the elutheroside E of this invention 1.

본 발명에 의하면, 안전하고 값이 싸며 일상적으로 섭취 가능한 골 강화용 소재 및 식품, 의약, 또는 사료를 제공하는 일을 할 수 있다.According to the present invention, it is possible to provide a safe, inexpensive and routinely ingestible bone strengthening material and food, medicine, or feed.

본 발명에 사용된 엘루테로사이드(eleutheroside) E는 흰털오가피에서 분리한 성분으로 성장기에 있는 정상적인 흰쥐의 성장에 대하여 골길이성장을 유의성있게 촉진시키는 작용효과를 보임으로서 골성장 촉진효과를 관찰할 수 있었고 골아세포 증식 촉진활성으로서 골강화작용 효과를 확인할 수 있다. Elutheheroside E used in the present invention can be observed as an ingredient that is isolated from the white hairy organs and shows an effect of promoting bone length growth significantly against the growth of normal rats in the growing season. And osteoblast proliferation promoting activity can be confirmed that the effect of strengthening bone.

또한, 본 발명의 골강화 조성물은 래트(rat)에 의한 실험에서 급성독성은 나타나지 않았다.  In addition, the osteoporosis composition of the present invention did not show acute toxicity in experiments by rats.

본 발명의 엘루테로사이드(eleutheroside) E는 투여 형태에 따라 여러 가지 형태로 제조될 수 있으며, 주사제, 분말(또는 과립), 드링크제, 정제, 캡슐제 등으로 이용하는 것이 가능하다.The eleutheroside E of the present invention can be prepared in various forms depending on the dosage form, and can be used as an injection, powder (or granule), drink, tablet, capsule, and the like.

본 발명의 엘루테로사이드(eleutheroside) E는, 주성분 및 보조 성분으로서 음식품에 넣어서 골 강화 식품으로 이용할 수 있으며, 부형제, 유화제, 안정제, 감미료, pH조정제, 증점제, 단백질, 펩티드(peptid), 아미노산, 지질, 다당류, 올리고당(oligosaccharide)등 통상 식품에 사용된 성분을 포함하고 있어도 좋다.The elutheroside E of the present invention can be used as a food fortifying foods as a main ingredient and an auxiliary ingredient, and can be used as food for strengthening, excipients, emulsifiers, stabilizers, sweeteners, pH adjusters, thickeners, proteins, peptides, amino acids , Lipids, polysaccharides, oligosaccharides and the like may be included in the usual food ingredients.

이하, 실시예를 들어 본 발명을 보다 상세히 설명하였다.Hereinafter, the present invention will be described in more detail with reference to Examples.

실시예 1 : 골아세포 증식 활성의 측정Example 1 Measurement of Osteoblast Proliferation Activity

엘루테로사이드(eleutheroside) E의 골아세포 증식 활성을 아래와 같이 측정하였다. 인간골아세포의 InM1.2 세포를 10% FBS를 포함한 α-MEM 배양액으로 37℃, 5% CO2-95%air의 조건하에서 배양한 후, 트립신(trypsin)을 처리하여 세포를 모으고, 상기 배양액을 이용하여 1×104cell/mL로 조제했다. 이 세포 조제액을 24-웰플레이트(well plate)에 0.5mL씩 분주하고 37℃, 5% CO2-95%air의 조건하에서 배양했다. 다음날, 시료가 100, 25, 12.5 ppm이 되도록 각 웰(well)에 첨가하고, 또 석회화 촉진제인 α-글리세롤 인산염 2mmol/L를 첨가했다. 시료는 50% DMSO에 녹여 용 매제가 배양액의 1%가 되도록 가했다. 배양액은 매일 교환하고, 20일 후에 MTT를 이용하여 골아세포의 수를 측정했다. 골아세포의 증식 촉진 활성은 대조군의 증식수를 100으로 했을 때의 상대 값으로 나타냈다. 이 결과를 표 1 로 나타낸다.Osteoblast proliferation activity of eleutheroside E was measured as follows. InM1.2 cells of human osteoblasts were incubated at 37 ° C. with 5% CO 2 -95% air in α-MEM medium containing 10% FBS, and then treated with trypsin to collect the cells. Was prepared at 1 × 10 4 cell / mL. 0.5 mL of this cell preparation was dispensed in a 24-well plate and incubated under 37 ° C and 5% CO 2 -95% air. The next day, the sample was added to each well so that it became 100, 25, and 12.5 ppm, and 2 mmol / L of alpha-glycerol phosphate which is a calcification promoter was added. Samples were dissolved in 50% DMSO and the solvent added to 1% of the culture. The cultures were exchanged daily and after 20 days the number of osteoblasts was measured using MTT. The proliferation promoting activity of osteoblasts was expressed as a relative value when the proliferation number of the control group was 100. The results are shown in Table 1.

대조군Control 골아세포 증식촉진활성 (대조군=100)Osteoblast proliferation promoting activity (control = 100) 25 ppm25 ppm 130.2±0.8130.2 ± 0.8 12.5 ppm12.5 ppm 127.9±0.5127.9 ± 0.5

실시예2 골 성장 촉진 활성Example 2 Bone Growth Promoting Activity

엘루테로사이드(eleutheroside) E의 골 성장 촉진 활성을 아래와 같이 측정하였다. 골 성장 촉진 활성은 스프라그-다울리(Sprague-Dawley)계 래트(rat)을 이용하여 평가했다. 시료를 0.5, 5 mg/ml의 농도로 증류수에 녹이고 래트(rat)에게 5 및 0.5 mg/kg체중/1일의 비율로 복강내투여하였다. 양성 대조군에는 성장호르몬을, 정상군에게는 동량의 생리식염수를 투여하였다. 시험기간 중 래트(rat)에게 물과 사료는 자유롭게 섭취하도록 하였다. 시료 섭취 기간(6일) 중 3 일째와 5 일째에 각각 형광 물질인 테트라사이클린(tetracycline)을 10mg/ml의 농도로 생리식염수에 녹여 20mg/kg의 용량으로 투여했다. 이 실시예에 있어서 테트라사이클린(tetracycline)이 칼슘(calcium)과 킬레이트(chelate)결합하여, 골에 침착되는 현상을 이용하고, 골에 형성된 형광 라인(line)를 관찰하여 경골의 엘루테로사이드(eleutheroside) E에 의한 성장 촉진 효과를 측정했다. 경골을 적출하여, 테트라사이클린(tetracycline)의 투여에 의해 경골 성장판의 하부와 골 신생부에 형성된 각 형광 선간의 길이, 즉 성장한 길이를 측정했다. 엘루테로사이드(eleutheroside) E 투여군과 대조군의 뼈의 신장을 비교하고 촉진 효과를 평가했다. 현미경 관찰의 결과, 엘루테로사이드(eleutheroside) E투여군은 컨트롤(control)군에 대해 두 층의 염색 밴드(band)의 간격이 평균적으로 60.9um가 넓어, 골 신장 촉진 활성이 있다고 확인됐다(도 1).The bone growth promoting activity of elutheroside E was measured as follows. Bone growth promoting activity was assessed using Sprague-Dawley rats. Samples were dissolved in distilled water at concentrations of 0.5 and 5 mg / ml and rats were intraperitoneally administered at rates of 5 and 0.5 mg / kg body weight / day. Growth hormone was administered to the positive control group and normal saline to the normal group. Rats were given free intake of water and feed during the trial. On days 3 and 5 of the sample ingestion period (6 days), tetracycline, a fluorescent substance, was dissolved in physiological saline at a concentration of 10 mg / ml and administered at a dose of 20 mg / kg. In this embodiment, tetracycline chelates with calcium, utilizes a phenomenon in which it is deposited on bone, and observes a fluorescence line formed in the bone, thereby eleutheroside of tibia. ) The growth promoting effect by E was measured. The tibia was removed, and the length between each fluorescent line formed at the lower part of the tibial growth plate and the bone angiogenesis, ie, the grown length, was measured by administration of tetracycline. The elongation of bone in the elutheroside E-administered group and the control group was compared and the promoting effect was evaluated. As a result of the microscopic observation, it was confirmed that the eluteheroside E-administered group had an average 60.9um wide interval between two layers of the dye bands for the control group, thereby promoting bone resorption activity (FIG. 1). ).

실시예3 (주사제)Example 3 (Injectable)

엘루테로사이드(eleutheroside) E 50mgEluteroside E 50 mg

소디움 메타비설파이트 3.0mgSodium Metabisulfite 3.0mg

메틸파라벤 0.8mgMethylparaben 0.8mg

프로필파라벤 0.1mgPropylparaben 0.1mg

주사용 멸균증류수 적량Proper sterile distilled water for injection

상기의 성분을 혼합하고 통상의 방법으로 2ml로 한 후 2ml용량의 앰플에 충전하고 멸균하여 주사제를 제조한다.The above ingredients are mixed, prepared in 2 ml by a conventional method, and filled into 2 ml ampoules and sterilized to prepare an injection.

실시예4 (정제)Example 4 (Tablet)

엘루테로사이드(eleutheroside) E 50mgEluteroside E 50 mg

유당 100mgLactose 100mg

전분 100mgStarch 100mg

스테아린산 마그네슘 적량Magnesium stearate proper amount

상기의 성분을 혼합하고 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.The above components are mixed and tableted according to a conventional method for producing tablets to produce tablets.

실시예5 (캡슐제)Example 5 (Capsules)

엘루테로사이드(eleutheroside) E 50mgEluteroside E 50 mg

유당 50mgLactose 50mg

전분 50mgStarch 50mg

탈크 2mgTalc 2mg

스테아린산마그네슘 적량Magnesium stearate appropriate amount

상기의 성분을 혼합하고 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.Capsules are prepared by mixing the above ingredients and filling into gelatin capsules according to a conventional method for preparing capsules.

실시예6 (액제)Example 6 (Liquid)

엘루테로사이드(eleutheroside) E 50mgEluteroside E 50 mg

설탕 20g20 g of sugar

이성화당 20g20 g of isomerized sugar

레몬향 적량Lemon flavor

정제수를 가하여 전체 100mlAdd 100 ml of purified water

상기의 성분을 통상의 액제의 제조방법에 따라서 혼합하고 100ml 의 갈색병에 충전하고 멸균시켜서 액제를 제조한다.The above components are mixed according to a conventional method for preparing a liquid, filled into a 100 ml brown bottle, and sterilized to prepare a liquid.

실시예7 (청량 음료수)Example 7 (soft drinks)

엘루테로사이드(eleutheroside) E 2%Elutheroside E 2%

혼합 이성화당 15.0%, 15.0% of mixed isomers,

과즙 10%, 10% fruit juice,

향료 0.1%, 0.1% fragrance,

칼슘(calcium) 0.1%, Calcium 0.1%,

물 72.8% 72.8% of water

상기의 성분을 를 혼합하고, 플레이트(plate) 살균기를 이용, 90℃에서 15초간 살균하여 청량 음료수를 제조한다.The above ingredients are mixed and sterilized at 90 ° C. for 15 seconds using a plate sterilizer to prepare a soft drink.

이상과 같이, 본 발명의 엘루테로사이드(eleutheroside) E는, 골아세포 증식 촉진 및 석회화 촉진 활성을 갖는다. 또한, 연골 세포의 증식을 촉진하고 뼈의 성장을 촉진하는 활성을 가지고 있다. 또, 캡슐(capsule), 정제 등에 보충제(supplement)로서 이용하는 것도 가능하고, 골다공증의 예방 및 증상 개선을 목적으로 한 음식품, 의약 또는 사료의 소재로서 유용하다. 과즙 등의 음료, 비스킷(biscuit) 등의 과자, 냉동 식품 등 각종 형태의 음식품에 첨가하여 골 강화 작용을 갖는 음식품으로도 만들 수 있다.As described above, the elutheroside E of the present invention has osteoblast proliferation promoting and calcification promoting activities. In addition, it has the activity of promoting the proliferation of chondrocytes and the growth of bone. It can also be used as a supplement for capsules, tablets and the like, and is useful as a material for food and drink, medicine or feed for the purpose of preventing osteoporosis and improving symptoms. It can be added to various types of food and beverages, such as juices, juices, biscuits and the like, and frozen foods, to produce foods having a bone strengthening effect.

Claims (1)

골아세포 증식촉진, 골성장 및 골강화 작용을 갖는 엘루테로사이드(eleutheroside) E를 유효성분으로 함유하는 골성장 촉진용 약학조성물.A pharmaceutical composition for promoting bone growth, which contains elutheroside E having an osteoblast proliferation, bone growth, and bone strengthening effect as an active ingredient.
KR1020060020790A 2006-03-06 2006-03-06 Pharmacuetical compositions comprising Eleutheroside E having bone growth-promoting effects KR100597564B1 (en)

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KR100842785B1 (en) * 2007-04-25 2008-07-01 주식회사 동원에프앤비 A pharmaceutical composition comprising eleutheroside b for treating and preventing bone disease

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KR101536231B1 (en) * 2014-09-05 2015-07-15 한국식품연구원 Composition for Preventing or Treating Insulin Resistance or Insulin Resistance-Related Diseases Comprising Eleutheroside E

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100842785B1 (en) * 2007-04-25 2008-07-01 주식회사 동원에프앤비 A pharmaceutical composition comprising eleutheroside b for treating and preventing bone disease

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