KR102448274B1 - Composition for preventing, ameliorating or treating bone disease comprising crude polysaccharide fraction of Psoralea corylifolia extract as effective component - Google Patents
Composition for preventing, ameliorating or treating bone disease comprising crude polysaccharide fraction of Psoralea corylifolia extract as effective component Download PDFInfo
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- KR102448274B1 KR102448274B1 KR1020220056660A KR20220056660A KR102448274B1 KR 102448274 B1 KR102448274 B1 KR 102448274B1 KR 1020220056660 A KR1020220056660 A KR 1020220056660A KR 20220056660 A KR20220056660 A KR 20220056660A KR 102448274 B1 KR102448274 B1 KR 102448274B1
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- South Korea
- Prior art keywords
- crude polysaccharide
- bone
- bogolji
- hot water
- polysaccharide fraction
- Prior art date
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Abstract
Description
본 발명은 보골지 추출물의 조다당 분획물을 유효성분으로 함유하는 골질환의 예방, 개선 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prevention, improvement or treatment of bone diseases containing the crude polysaccharide fraction of the bogolji extract as an active ingredient.
골은 석회화된 견고한 표면과 골수로 불리는 내부의 세포 성분이 결합된 특수조직이다. 생리적으로 상이한 이 두 구조의 결합은 일생을 두고 지속되는 골의 재형성(bone remodeling) 과정에 기인한 것인데，이는 골에 가해지는 호르몬이나 물리적 자극에 의해 골수에 있는 파골세포(osteoclast)들이 골의 표면으로 모여 골을 파고 들어가면서 파괴하는 골흡수(bone resorption)가 일어난 자리에 모여든 조골세포(osteoblast)에 의한 골기질의 합성(bone formation)으로 설명된다.Bone is a special tissue composed of a solid calcified surface and an internal cellular component called bone marrow. The combination of these two physiologically different structures is due to the process of bone remodeling that lasts a lifetime. It is explained as the synthesis of the bone matrix by the osteoblasts gathered at the site where the bone resorption, which gathers to the surface and destroys the bone while digging into it, has occurred.
골은 조골세포와 파골세포 활성의 균형을 유지함으로 골량을 일정하게 유지하며, 이들의 활성으로 골의 재생이 지속적으로 일어난다. 그러나 조골세포보다 파골세포의 활성이 증가하면 골량이 감소하여 골다공증이 유발된다.Bone maintains a constant bone mass by balancing the activity of osteoblasts and osteoclasts, and bone regeneration occurs continuously through these activities. However, when the activity of osteoclasts rather than osteoblasts is increased, bone mass decreases and osteoporosis is induced.
골질환 중 현재 가장 중요한 사회적 문제 중 하나인 골다공증은 낮은 골양과 골기질의 파괴로 골절의 위험과 골의 취약성이 증가되는 골격질환을 말한다. 골다공증은 폐경기 이후 여성에서 특히 빈번하게 발생하며, 이는 에스트로겐의 분비 감소에 의하여 뼈의 양이 현저하게 감소되는 질환이다. Osteoporosis, one of the most important social problems among bone diseases, refers to a skeletal disease in which the risk of fracture and bone fragility increase due to low bone mass and destruction of bone matrix. Osteoporosis occurs particularly frequently in postmenopausal women, which is a disease in which the amount of bone is significantly reduced due to a decrease in estrogen secretion.
골다공증은 그 자체보다는 뼈의 약화에 따라 초래되는 각종 골절, 특히 대퇴골 골절 또는 척추골절이 더 문제가 되며, 골절로 인하여 장기간 활동을 제한하여 건강한 생활을 영위할 수 없게 되고, 노인층 사망의 15%에 대한 원인이 되는 것으로 알려져 있다.Osteoporosis is a more problematic type of fractures caused by weakening of bones rather than by itself, especially femur fractures or vertebral fractures. known to cause
현재 골다공증 치료제로 사용되고 있는 물질로는 에스트로겐(estrogen), 남성화 스테로이드 호르몬(androgenic anabolic steroid), 칼슘 제제, 인산염, 불소 제제, 이프리플라본(Ipriflavone), 비타민 D3 등이 있다. 에스트로겐이나 골다공증 치료제로 알려진 에스트라디올(Estradiol)은 조골세포의 세포 고사를 억제하여 세포의 생존기간을 증가시키고 파골세포의 세포 고사를 촉진하여 세포의 생존기간을 감소시켜 폐경 증상의 치료와 골밀도 유지에 어느 정도 효과적인 방법이나 유방암, 자궁내막 증식증 등을 유발하는 부작용이 있다.Materials currently used for the treatment of osteoporosis include estrogen, androgenic anabolic steroids, calcium preparations, phosphates, fluoride preparations, Ipriflavone, vitamin D3, and the like. Estradiol, known as an estrogen or osteoporosis treatment, is effective in the treatment of menopausal symptoms and maintenance of bone density by inhibiting osteoblast apoptosis and increasing the cell survival period and promoting osteoclast apoptosis to reduce the cell survival period. Although it is an effective method to some extent, there are side effects that cause breast cancer and endometrial hyperplasia.
골다공증은 약물의 단기 투여만으로는 치료할 수 없고 약물의 장기 투여가 필수적인 질환이므로, 약물을 장기 투여할 때에도 상기와 같은 부작용이 없고 에스트로겐을 대체할 수 있을 만큼 우수한 약효를 갖는 새로운 물질의 개발이 요구되고 있다. 이에 따라, 장기간 복용할 수 있고 상대적으로 부작용이 적은 골다공증 예방 및 치료제를 개발하고자 많은 연구가 진행중이다.Osteoporosis cannot be cured by short-term administration of drugs alone, and long-term administration of drugs is essential. Therefore, even when drugs are administered for a long period of time, there is no side effect as described above, and development of new substances with excellent drug efficacy to replace estrogen is required. . Accordingly, many studies are being conducted to develop a preventive and therapeutic agent for osteoporosis that can be taken for a long time and has relatively few side effects.
한편, 보골지(Psoraleae Semen)는 콩과(Leguminosae)에 속하는 보골지(Psoralea coylifolia L.)의 씨를 일컫는 것으로, 보골지라는 이름은 효능을 뜻하는 말이며, 파고지는 잘못 발음하여 생긴 말이다. 보골지 씨는 방향이 있고, 맛은 맵고 쓰며 성질은 따듯하다. 보골지는 신장의 양기를 보해 음부가 차고, 유정, 유뇨, 허리 통증이 있을 때 쓰며 비위허한으로 음식량이 감소하고 헛배가 부를 때, 그리고 장에서 소리가 나고 구역질, 설사, 소변을 자주 보러 다닐 때 사용한다. On the other hand, Bogolji ( Psoraleae Semen ) refers to the seeds of Bogolji ( Psoralea coylifolia L. ) belonging to the leguminosae family. Bogolji seeds have an aroma, taste spicy and bitter, and have a warm nature. Bogolji protects the yang of the kidneys and is used when the genitals are cold, oily, enuresis, and back pain. use.
보골지의 약리작용으로 관상동맥 확장 작용, 혈류량 증가 작용, 백혈구 수 증가 작용, 평활근 흥분 작용, 조혈 작용, 항노쇠 작용, 항암 작용, 자외선 과민물질 흡수 및 국부 조직 영양 개선이 보고되었다.As pharmacological actions of Bogolji, coronary artery dilatation, blood flow increase, white blood cell count increase, smooth muscle excitability, hematopoiesis, anti-senescence, anticancer, ultraviolet sensitizer absorption and improvement of local tissue nutrition have been reported.
생김새는 콩팥 모양이며 조금 납작하고 바깥 면은 흑색, 흑갈색 또는 회갈색으로 그물 모양의 작은 무늬가 있다. 위쪽은 둥글고 1개의 작은 돌기가 있으며 과병 자국은 움푹 들어가 있다. 절단면은 황백색이며 떡잎이 2개 있고 기름기가 있다.The appearance is kidney-shaped, a little flat, and the outer surface is black, blackish-brown or grayish-brown, with small net-like patterns. The upper part is round and there is one small protrusion, and the peduncles are dented. The cut surface is yellowish white, has 2 cotyledons, and is oily.
한편, 골질환과 관련된 선행기술로는 한국등록특허 제2214406호에 호박덩굴손 유래 신규화합물을 유효성분으로 포함하는 골질환 예방 및 치료용 약학 조성물이 개시되어 있고, 한국등록특허 제2334305호에 블루베리 추출물을 함유하는 골질환 예방 또는 치료용 조성물이 개시되어 있지만, 본 발명의 보골지 추출물의 조다당 분획물을 유효성분으로 함유하는 골질환의 예방, 개선 또는 치료용 조성물에 대해 개시된 바 없다. On the other hand, as a prior art related to bone disease, Korean Patent No. 2214406 discloses a pharmaceutical composition for preventing and treating bone disease containing a novel compound derived from amber tendril as an active ingredient, and Korean Patent No. 2334305 discloses blueberry Although a composition for preventing or treating bone disease containing the extract is disclosed, there is no disclosure of a composition for preventing, improving or treating bone disease containing the crude polysaccharide fraction of the bogolji extract of the present invention as an active ingredient.
본 발명은 상기와 같은 요구에 의해 도출된 것으로, 보골지(Psoralea corylifolia) 추출물의 조다당 분획물을 유효성분으로 함유하는 골질환의 예방, 개선 또는 치료용 조성물을 제공하고, 상기 보골지 추출물의 조다당 분획물이 보골지 열수 추출물 또는 보골지 열수 추출물에서 조다당이 제외된 분획물에 비해 파골세포 분화 억제능이 현저하고, 동물모델에서 대조군 대비 보골지 열수 추출물의 조다당 분획물 투여군의 골소실이 현저히 완화하는 것을 확인함으로써, 본 발명을 완성하였다.The present invention has been derived by the above needs, and provides a composition for preventing, improving or treating bone diseases containing the crude polysaccharide fraction of the bogolji extract as an active ingredient, and the composition of the bogolji extract The polysaccharide fraction showed a remarkable ability to inhibit osteoclast differentiation compared to the fraction in which crude polysaccharide was excluded from the Bogolji hot water extract or the Bogolji hot water extract, and the bone loss of the group administered with the crude polysaccharide fraction of the Bogolji hot water extract compared to the control group was significantly alleviated in animal models. By confirming that, the present invention was completed.
상기 과제를 해결하기 위하여, 본 발명은 보골지(Psoralea corylifolia) 추출물의 조다당 분획물을 유효성분으로 함유하는 골질환의 예방 또는 치료용 약학 조성물을 제공한다. In order to solve the above problems, the present invention provides a pharmaceutical composition for the prevention or treatment of bone diseases containing the crude polysaccharide fraction of the bogolji ( Psoralea corylifolia ) extract as an active ingredient.
또한, 본 발명은 보골지(Psoralea corylifolia) 추출물의 조다당 분획물을 유효성분으로 함유하는 골질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다. In addition, the present invention provides a health functional food composition for the prevention or improvement of bone disease containing the crude polysaccharide fraction of the bogolji ( Psoralea corylifolia ) extract as an active ingredient.
또한, 본 발명은 보골지(Psoralea corylifolia) 추출물의 조다당 분획물을 유효성분으로 함유하는 골질환의 예방 또는 개선용 사료 첨가제를 제공한다. In addition, the present invention provides a feed additive for preventing or improving bone disease containing the crude polysaccharide fraction of the bogolji ( Psoralea corylifolia ) extract as an active ingredient.
본 발명은 보골지(Psoralea corylifolia) 추출물의 조다당 분획물을 유효성분으로 함유하는 골질환의 예방, 개선 또는 치료용 조성물에 관한 것으로, 보골지 열수 추출물; 또는 보골지 열수 추출물에서 조다당이 제외된 분획물;에 비해 보골지 추출물의 조다당 분획물의 TRAP 활성 억제 효과가 현저하였을 뿐 아니라, 본 발명의 보골지 추출물의 조다당 분획물의 파골세포 분화 억제 효과를 확인하였을 때, 30kDa 미만의 분자량을 가지는 조다당 분획물에 비해 30kDa 이상의 분자량을 가지는 조다당 분획물에서 현저한 TRAP 활성 억제 효과가 있다. 또한, 난소를 절제한 골소실 동물모델에서 보골지 추출물의 조다당 분획물의 투여는 골소실을 완화하는 효과가 있다. The present invention relates to a composition for the prevention, improvement or treatment of bone diseases containing a crude polysaccharide fraction of the bogolji ( Psoralea corylifolia ) extract as an active ingredient, the bogolji hot water extract; Alternatively, the crude polysaccharide fraction of the Bogolji extract showed a remarkable TRAP activity inhibitory effect as compared to the fraction in which the crude polysaccharide was excluded from the Bogolji hot water extract, and the osteoclast differentiation inhibitory effect of the crude polysaccharide fraction of the Bogolji extract of the present invention was significantly improved. When confirmed, there is a significant TRAP activity inhibitory effect in the crude polysaccharide fraction having a molecular weight of 30 kDa or more compared to the crude polysaccharide fraction having a molecular weight less than 30 kDa. In addition, administration of the crude polysaccharide fraction of the bogolji extract has an effect of alleviating bone loss in an animal model of bone loss from which the ovaries have been resected.
도 1은 보골지 열수 추출물(WEPC), 보골지 열수 추출물의 조다당 분획물(WEPC-PO) 및 보골지 열수 추출물의 조다당 제외 분획물(WEPC-ED)의 파골세포 분화 억제능을 확인한 결과이다. *, **은 아무것도 처리하지 않은 군(0)에 비해 TRAP 활성이 통계적으로 유의미하게 감소하였다는 것을 의미하며, *은 p<0.05, **은 p<0.01이다.
도 2는 보골지 열수 추출물(WEPC), 보골지 열수 추출물의 조다당 분획물(WEPC-PO) 및 보골지 열수 추출물의 조다당 제외 분획물(WEPC-ED)이 파골세포 전구세포(마우스 골수세포 유래 대식세포)의 세포 생존에 미치는 영향을 확인한 결과이다.
도 3은 조다당 분자량에 따른 보골지 열수 추출물의 조다당 분획물의 파골세포 분화 억제능을 확인한 결과이다. 3kDa Fx는 3kDa 이상의 분자량을 가지는 조다당을 모두 포함하는 분획물이고, 10kDa Fx는 10kDa 이상의 분자량을 가지는 조다당을 모두 포함하는 분획물이고, 30kDa Fx는 30kDa 이상의 분자량을 가지는 조다당을 모두 포함하는 분획물이고, 100kDa Fx는 100kDa 이상의 분자량을 가지는 조다당을 모두 포함하는 분획물이고, 300kDa Fx는 300kDa 이상의 분자량을 가지는 조다당을 모두 포함하는 분획물이며, 1000kDa Fx는 1000kDa 이상의 분자량을 가지는 조다당을 모두 포함하는 분획물이다. *, **은 아무것도 처리하지 않은 군(0)에 비해 TRAP 활성이 통계적으로 유의미하게 감소하였다는 것을 의미하며, *은 p<0.05, **은 p<0.01이다.
도 4는 난소절제(OVX) 마우스 골소실 모델에서 보골지 추출물의 조다당 분획물(WEPC-PO)의 구강 투여에 따른 대퇴 해면골의 골밀도(BMD, a), 골체적(BV/TV, b) 및 골두께(Tb.Th, c) 변화를 확인한 결과이다. Sham은 난소를 절제하지 않은 정상 동물모델이다. **은 WEPC-PO를 투여하지 않은 난소절제 동물모델 대비 Sham군 및 WEPC-PO를 투여한 난소절제 동물모델 군의 골밀도 및 골체적이 통계적으로 유의미하게 증가된 것을 의미하며, p<0.01이다. 또한, 도면 내 서로 다른 문자 a~c는 서로 통계적으로 유의미한 차이가 있다는 것을 의미하며, p<0.05이다. 1 is a result confirming the osteoclast differentiation inhibitory ability of a bogolji hot water extract (WEPC), a crude polysaccharide fraction (WEPC-PO) of a bogolji hot water extract, and a crude polysaccharide fraction (WEPC-ED) of a bogolji hot water extract. * and ** mean that the TRAP activity was statistically significantly decreased compared to the group that was not treated with anything (0), * is p<0.05, ** is p<0.01.
Figure 2 shows that osteoclast progenitor cells (mouse bone marrow cell-derived vs. This is the result of confirming the effect on cell survival of phagocytes).
3 is a result confirming the osteoclast differentiation inhibitory ability of the crude polysaccharide fraction of Bogolji hot water extract according to the molecular weight of the crude polysaccharide. 3kDa Fx is a fraction including all crude polysaccharides having a molecular weight of 3 kDa or more, 10 kDa Fx is a fraction including all crude polysaccharides having a molecular weight of 10 kDa or more, and 30 kDa Fx is a fraction including all crude polysaccharides having a molecular weight of 30 kDa or more. , 100kDa Fx is a fraction containing all crude polysaccharides having a molecular weight of 100 kDa or more, 300 kDa Fx is a fraction containing all crude polysaccharides having a molecular weight of 300 kDa or more, and 1000 kDa Fx is a fraction containing all crude polysaccharides having a molecular weight of 1000 kDa or more to be. * and ** mean that the TRAP activity was statistically significantly decreased compared to the group that was not treated with anything (0), * is p<0.05, ** is p<0.01.
Figure 4 shows the bone density (BMD, a), bone volume (BV/TV, b) of cancellous femoral bone according to oral administration of the crude polysaccharide fraction (WEPC-PO) of the bogolji extract in an ovariectomized (OVX) mouse bone loss model. This is the result of confirming the change in bone thickness (Tb.Th, c). Sham is a normal animal model without ovarian resection. ** indicates a statistically significant increase in bone density and bone volume in the Sham group and in the ovariectomized animal model group administered with WEPC-PO compared to the ovariectomized animal model without WEPC-PO, and p<0.01. In addition, different letters a to c in the drawing mean that there is a statistically significant difference from each other, and p<0.05.
본 발명의 목적을 달성하기 위하여, 본 발명은 보골지(Psoralea corylifolia) 추출물의 조다당 분획물을 유효성분으로 함유하는 골질환의 예방 또는 치료용 약학 조성물을 제공한다. In order to achieve the object of the present invention, the present invention provides a pharmaceutical composition for the prevention or treatment of bone diseases containing the crude polysaccharide fraction of the bogolji ( Psoralea corylifolia ) extract as an active ingredient.
상기 보골지 추출물은 보골지의 씨앗에서 추출한 것이 바람직하지만, 이에 제한되지 않는다. The bogolji extract is preferably extracted from the seeds of bogolji, but is not limited thereto.
상기 보골지 추출물의 용매는 물, C1~C4의 저급 알코올 또는 이들의 혼합물일 수 있고, 바람직하게는 물이지만, 이에 제한되는 것은 아니다. The solvent of the bogolji extract may be water, a lower alcohol of C 1 to C 4 or a mixture thereof, preferably water, but is not limited thereto.
본 발명의 일 구현 예에서, 상기 보골지 추출물의 조다당 분획물 내의 조다당 분자량은 3kDa 이상인 것이 바람직하고, 더 바람직하게는 30kDa 이상인 것이며, 더욱더 바람직하게는 100kDa 이상인 것이지만, 이에 제한되는 것은 아니다. In one embodiment of the present invention, the molecular weight of the crude polysaccharide in the crude polysaccharide fraction of the Bogolji extract is preferably 3 kDa or more, more preferably 30 kDa or more, and even more preferably 100 kDa or more, but is not limited thereto.
본 발명의 일 구현 예에서, 상기 보골지 추출물의 조다당 분획물은 파골세포의 분화를 억제하고, 골형성을 촉진하는 효과가 있다. In one embodiment of the present invention, the crude polysaccharide fraction of the bogolji extract has the effect of inhibiting the differentiation of osteoclasts and promoting bone formation.
상기 골질환은 골소실에 의해 야기되는 것이 바람직하고, 구체적으로 상기 골질환은 골다공증, 골 소실증, 골연화증, 골 결손, 고관절 감소증 및 골 형성장애 중에서 선택된 어느 하나인 것이지만, 이에 한정하는 것은 아니다. The bone disease is preferably caused by bone loss, and specifically, the bone disease is any one selected from osteoporosis, bone loss, osteomalacia, bone defect, hip arthropathy, and bone dysplasia, but is not limited thereto.
본 발명의 조성물은 상기 유효성분 이외에 약학적으로 허용 가능한 담체, 부형제 또는 희석제를 더 포함할 수 있으며, 경구 또는 비경구의 여러 가지 제형일 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형 제제에는 캡슐제, 산제, 과립제, 정제, 환제 등이 포함되며, 이러한 고형 제제는 하나 이상의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한, 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제들도 사용된다. 경구 투여를 위한 액상 제제로는 현탁액, 에멀전, 시럽, 에어로졸 등이 해당되는데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성 용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성 용제 및 현탁 용제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로 젤라틴 등이 사용될 수 있다. 비경구 투여 시 피부 외용 또는 복강 내, 직장, 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관 내 주사 방식을 선택하는 것이 바람직하다.The composition of the present invention may further include a pharmaceutically acceptable carrier, excipient or diluent in addition to the active ingredient, and may be in various oral or parenteral formulations. In the case of formulation, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are usually used. Solid preparations for oral administration include capsules, powders, granules, tablets, pills, etc., and such solid preparations include at least one excipient in one or more compounds, for example, starch, calcium carbonate, sucrose or lactose ( lactose), gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral administration include suspensions, emulsions, syrups, aerosols, etc., and various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. in addition to water and liquid paraffin, which are commonly used simple diluents, may be included. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycero gelatin, etc. may be used. For parenteral administration, it is preferable to select an external skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dural, or intracerebrovascular injection method.
본 발명에 따른 약학 조성물은 약제학적으로 유효한 양으로 투여한다. 본 발명에 있어서, "약제학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효량의 수준은 환자의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and the level of the effective amount is determined by the type, severity, and drug activity of the patient. , sensitivity to drugs, administration time, administration route and excretion rate, duration of treatment, factors including concurrent drugs, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple. In consideration of all of the above factors, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, which can be easily determined by those skilled in the art.
본 발명의 조성물은 단독으로 또는 수술, 방사선 치료, 호르몬 치료, 화학치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.
또한, 본 발명은 보골지(Psoralea corylifolia) 추출물의 조다당 분획물을 유효성분으로 함유하는 골질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다. In addition, the present invention provides a health functional food composition for the prevention or improvement of bone disease containing the crude polysaccharide fraction of the bogolji ( Psoralea corylifolia ) extract as an active ingredient.
본 발명의 일 구현 예에서, 상기 건강기능식품 조성물은 분말, 과립, 환, 정제, 캡슐, 캔디, 시럽 또는 음료의 제형으로 제조되는 것이 바람직하지만, 이에 제한되지 않는다. In one embodiment of the present invention, the health functional food composition is preferably prepared in the form of powder, granule, pill, tablet, capsule, candy, syrup or beverage, but is not limited thereto.
본 발명의 건강기능식품 조성물을 식품첨가물로 사용하는 경우, 상기 유효성분을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 그의 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 조성물은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 그러나 건강 및 위생을 목적으로 하거나 건강 조절을 목적으로 하는 장기간의 섭취인 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다. When the health functional food composition of the present invention is used as a food additive, the active ingredient may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of its use (prophylactic, health or therapeutic treatment). In general, in the production of food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw material. However, in the case of long-term ingestion for health and hygiene purposes or health control, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
상기 식품의 종류에는 특별한 제한은 없다. 상기 유효성분을 첨가할 수 있는 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 수프, 음료수, 차, 드링크제, 알코올음료 및 비타민 복합체 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.There is no particular limitation on the type of the food. Examples of foods to which the active ingredient can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks , alcoholic beverages and vitamin complexes, and includes all health functional foods in the ordinary sense.
본 발명의 조성물을 건강 음료로 사용할 경우, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 텍스트린, 사이클로텐스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100g당 일반적으로 약 0.01~0.04g, 바람직하게는 약 0.02~0.03g이다. 상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 중점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 조성물은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물은 100 중량부 당 0.01~0.1 중량부의 범위에서 선택되는 것이 일반적이다.When the composition of the present invention is used as a health drink, it may contain various flavoring agents or natural carbohydrates as an additional component like a conventional drink. The above-mentioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclotenstrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as taumatine and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 g of the composition of the present invention. In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal central agents, pH regulators, stabilizers, preservatives, glycerin, alcohol , a carbonation agent used in carbonated beverages, and the like. In addition, the composition of the present invention may contain fruit for the production of natural fruit juice, fruit juice beverage, and vegetable beverage. These components may be used independently or in combination. The proportion of these additives is not very important, but the composition of the present invention is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight.
또한, 본 발명은 보골지(Psoralea corylifolia) 추출물의 조다당 분획물을 유효성분으로 함유하는 골질환의 예방 또는 개선용 사료 첨가제에 관한 것이다. In addition, the present invention relates to a feed additive for the prevention or improvement of bone disease containing the crude polysaccharide fraction of the bogolji ( Psoralea corylifolia ) extract as an active ingredient.
본 발명의 사료 첨가제는 사료관리법상의 보조사료에 해당한다. 본 발명에서 용어 '사료'는 동물이 먹고, 섭취하며, 소화시키기 위한 또는 이에 적당한 임의의 천연 또는 인공 규정식, 한끼식 등 또는 상기 한끼식의 성분을 의미할 수 있다. 상기 사료의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용되는 사료를 사용할 수 있다. 상기 사료의 비제한적인 예로는, 곡물류, 근과류, 식품 가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류 또는 곡물 부산물류 등과 같은 식물성 사료; 단백질류, 무기물류, 유지류, 광물성류, 유지류, 단세포 단백질류, 동물성 플랑크톤류 또는 음식물 등과 같은 동물성 사료를 들 수 있다. 이들은 단독으로 사용되거나 2종 이상을 혼합하여 사용될 수 있다.The feed additive of the present invention corresponds to an auxiliary feed under the Feed Management Act. In the present invention, the term 'feed' may mean any natural or artificial diet, one-meal meal, etc., or a component of the one-meal meal, for or suitable for animal eating, ingestion, and digestion. The type of feed is not particularly limited, and feed commonly used in the art may be used. Non-limiting examples of the feed include plant feeds such as grains, root fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, gourds or grain by-products; and animal feeds such as proteins, inorganic materials, oils and fats, minerals, oils and fats, single cell proteins, zooplankton, or food. These may be used alone or in combination of two or more.
이하, 제조예 및 실시예를 이용하여 본 발명을 더욱 상세하게 설명하고자 한다. 이들 제조예 및 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 범위가 이들에 의해 제한되지 않는다는 것은 당해 기술분야에서 통상의 지식을 가진 자에게 있어 자명한 것이다. Hereinafter, the present invention will be described in more detail using Preparation Examples and Examples. These preparations and examples are only for explaining the present invention in more detail, and it is obvious to those of ordinary skill in the art that the scope of the present invention is not limited thereto.
제조예 1. 보골지 열수 추출물(WEPC)의 제조Preparation Example 1. Preparation of bogolji hot water extract (WEPC)
보골지 열수 추출물(WEPC)은 보골지 1kg을 증류수 10ℓ에 넣고 3시간 동안 환류추출 후 솜필터로 여과하여 제조하였다.Bogolji hot water extract (WEPC) was prepared by putting 1 kg of bogolji in 10 liters of distilled water, extracting it under reflux for 3 hours, and then filtering it with a cotton filter.
제조예 2. 보골지 열수 추출물의 조다당 분획물(WEPC-PO) 및 조다당 제외 분획물(WEPC-ED)의 제조Preparation Example 2. Preparation of the crude polysaccharide fraction (WEPC-PO) and the crude polysaccharide fraction (WEPC-ED) of the bogolji hot water extract
보골지 열수 추출물의 조다당 분획물을 제조하기 위해, 상기 제조예 1의 보골지 열수 추출물에 에탄올을 첨가하여 80%(v/v) 에탄올이 되게 하여, 당 성분을 침전시켰다. 침전된 물질은 분리하여 보골지 조다당 분획물(WEPC-PO)로 사용하였고, 침전되지 않은 부분을 조다당 제외 분획물(WEPC-ED)로서, 실험에 사용하였다. In order to prepare the crude polysaccharide fraction of the Bogolji hot water extract, ethanol was added to the Bogolji hot water extract of Preparation Example 1 to become 80% (v/v) ethanol, thereby precipitating the sugar component. The precipitated material was separated and used as a Bogolji crude polysaccharide fraction (WEPC-PO), and the non-precipitated portion was used as a crude polysaccharide-excluded fraction (WEPC-ED) for the experiment.
제조예 3. 조다당 분획물(WEPC-PO)의 분자량별 분획물의 제조Preparation Example 3. Preparation of fractions by molecular weight of crude polysaccharide fraction (WEPC-PO)
조다당 분자량별 분획물을 제조하기 위해, 상기 보골지 조다당 분획물 (WEPC-PO)을 분획분자량(molecular weight cut-off) 3, 10, 30, 100, 300 및 1000 kDa 인 여과막을 사용하여 각 크기 이상의 분자량으로 통과하지 않은 각 분획물인 3kDa Fx, 10kDa Fx, 30kDa Fx, 100kDa Fx, 300kDa Fx 및 1000kDa Fx를 획득하였다.In order to prepare fractions for each molecular weight of crude polysaccharide, the Bogolji crude polysaccharide fraction (WEPC-PO) was subjected to molecular weight cut-off of 3, 10, 30, 100, 300 and 1000 kDa using a filtration membrane of each size. 3kDa Fx, 10kDa Fx, 30kDa Fx, 100kDa Fx, 300kDa Fx, and 1000kDa Fx, each of the fractions that did not pass with a molecular weight higher than that, were obtained.
실시예 1. 보골지 조다당 분획물의 성분 분석Example 1. Analysis of components of bogolji crude polysaccharide fraction
상기 제조예 2의 보골지 열수 추출물의 조다당 분획물의 주요 성분 및 구성당 조성을 총 당 정량법(Phenol sulfuric acid method)을 이용하여 분석하였다. 단백질은 브래드포드 분석(bradford assay)을 이용하여 분석하였고, 조지질(crude lipid)은 Bligh & Dyer 방법을 이용하여 분석하였으며, 우론산(uronic acid)은 카바졸 분석(carbazole assay)을 이용하여 확인하였다. 당 구성은 HPAEC-PAD 방법을 이용하여 분석하였다. The main components and constituent sugars of the crude polysaccharide fraction of the Bogolji hot water extract of Preparation Example 2 were analyzed using the total sugar quantification method (Phenol sulfuric acid method). Proteins were analyzed using Bradford assay, crude lipids were analyzed using Bligh & Dyer method, and uronic acid was confirmed using carbazole assay. did. Sugar composition was analyzed using the HPAEC-PAD method.
그 결과, 하기 표 1에 개시된 바와 같으며, 화학 조성 함량비(%)는 건조 시료 내의 비율을 나타낸 것이고, mole%는 검출된 총 탄수화물의 양으로부터 계산하였다. 본 발명의 조다당 분획물에는 다당류 외에도 일부 조지방 및 단백질을 함유하며, 그 함량은 각각 25.43% 및 5.47%로 나타났다. 또한, 본 발명의 보골지 조다당 분획물의 구성당은 주로 갈락토오스 및 글루코오스였다.As a result, as shown in Table 1 below, the chemical composition content ratio (%) indicates the ratio in the dry sample, and the mole % was calculated from the amount of total carbohydrates detected. The crude polysaccharide fraction of the present invention contains some crude fat and protein in addition to polysaccharides, and the content thereof was found to be 25.43% and 5.47%, respectively. In addition, the constituent sugars of the bogolgi crude polysaccharide fraction of the present invention were mainly galactose and glucose.
실시예 2. 파골세포 분화에 대한 효과 분석(TRAP 활성도 측정)Example 2. Analysis of effects on osteoclast differentiation (measurement of TRAP activity)
상기 제조예 1의 보골지 열수 추출물(WEPC)과 상기 제조예 2의 보골지 열수 추출물의 조다당 분획물(WEPC-PO) 및 조다당 제외 분획물(WEPC-ED)이 파골세포의 전구세포가 파골세포로 분화하는 것을 억제하는지를 확인하고자, 파골세포 전구세포에 상기 제조예 1 및 2의 시료를 농도별로 처리하고 TRAP 활성도를 측정하였다. The crude polysaccharide fraction (WEPC-PO) and the crude polysaccharide-excluded fraction (WEPC-ED) of the Bogolji hot water extract of Preparation Example 1 (WEPC) and the Bogolji hot water extract of Preparation Example 2 are osteoclast precursor cells In order to check whether or not to inhibit differentiation into osteoclasts, the samples of Preparation Examples 1 and 2 were treated for each concentration and TRAP activity was measured.
구체적으로, 마우스의 골수 세포를 M-CSF(60ng/㎖)와 10% FBS를 함유한 α-MEM 배지에 3일 동안 배양하여 골수세포 유래 대식세포(BMM)를 수득하여 이를 파골세포 전구세포로 사용하였다. 파골세포를 생성하기 위해, 96웰 플레이트의 웰당 1×104개의 상기 수득한 골수세포 유래 대식세포를 넣은 후 M-CSF(60ng/㎖) 및 RANKL(50ng/㎖)을 포함하는 배지에 4일 동안 배양하였고, 동일한 배양조건에서 BMM에 상기 제조예 1 및 2의 시료를 농도별로 처리하였다. 이후, 세포를 10% 포르말린으로 고정한 후, 0.1% Triton X-100으로 투과(permeabilization) 시켰다. 파골세포 분화 정도를 확인하기 위해, 기질 파라-니트로페닐 포스페이트(para-nitrophenyl phosphate)을 사용하여 TRAP(Tartrate-resistant acid phosphatase) 활성도를 측정하였다.Specifically, bone marrow cells of mice were cultured in α-MEM medium containing M-CSF (60ng/ml) and 10% FBS for 3 days to obtain bone marrow cell-derived macrophages (BMM), which were then transformed into osteoclast progenitors. was used. In order to generate osteoclasts, 1×10 4 cells of the obtained bone marrow cell-derived macrophages per well of a 96-well plate were placed in a medium containing M-CSF (60 ng/ml) and RANKL (50 ng/ml) for 4 days. The samples of Preparation Examples 1 and 2 were treated by concentration in BMM under the same culture conditions. Thereafter, the cells were fixed with 10% formalin, and then permeabilized with 0.1% Triton X-100. To determine the degree of osteoclast differentiation, the substrate para-nitrophenyl phosphate was used to measure tartrate-resistant acid phosphatase (TRAP) activity.
그 결과, 도 1에 개시된 바와 같이 보골지 열수 추출물(WEPC); 및 보골지 열수 추출물의 조다당 분획물(WEPC-PO);은 보골지 열수 추출물의 조다당 제외 분획물(WEPC-ED);에 비해 TRAP 활성을 억제하는 효과가 우수하였고, 특히 보골지 열수 추출물의 조다당 분획물은 동일 농도에서 보골지 열수 추출물에 비해 TRAP 활성을 억제하는 효과가 현저하였다. 이로부터 파골세포 분화를 억제하는 물질이 보골지 열수 추출물의 조다당 분획물에 풍부하게 포함되어 있다는 것을 확인하였다. As a result, as disclosed in Figure 1, Bogolji hot water extract (WEPC); and the crude polysaccharide fraction (WEPC-PO) of the bogolji hot water extract; the crude polysaccharide fraction of the bogolji hot water extract (WEPC-ED); The polysaccharide fraction had a significant inhibitory effect on TRAP activity compared to the Bogolji hot water extract at the same concentration. From this, it was confirmed that substances that inhibit osteoclast differentiation were abundantly contained in the crude polysaccharide fraction of the hot water extract of Bogolji.
실시예 3. 보골지 추출물의 조다당 분획물이 세포 생존에 미치는 효과 분석Example 3. Analysis of the effect of the crude polysaccharide fraction of Bogolji extract on cell survival
상기 제조예 1의 보골지 열수 추출물(WEPC)과 상기 제조예 2의 보골지 열수 추출물의 조다당 분획물(WEPC-PO) 및 조다당 제외 분획물(WEPC-ED)이 파골세포 전구세포의 생존에 미치는 효과를 확인하고자 하였다.The effect of the crude polysaccharide fraction (WEPC-PO) and the crude polysaccharide-excluded fraction (WEPC-ED) of the Bogolji hot water extract of Preparation Example 1 (WEPC) and the Bogolji hot water extract of Preparation Example 2 on the survival of osteoclast progenitors The effect was to be confirmed.
구체적으로, 상기 실시예 2의 골수세포 유래 대식세포(BMM)를 96웰 플레이트의 웰당 2×104개 넣은 후 M-CSF(60ng/㎖)를 함유하는 배지에 1일 동안 다양한 농도의 시료를 첨가하여 배양하였다. 배양 후, 세포 계수 키트-8(Cell counting Kit-8, Dojindo Inc.)을 이용하여 450nm에서 흡광도를 측정하여 세포 생존율(Cell viability)을 확인하였다.Specifically, after putting 2 × 10 4 bone marrow cell-derived macrophages (BMM) of Example 2 per well of a 96-well plate, samples of various concentrations were added to a medium containing M-CSF (60 ng/ml) for 1 day. was added and cultured. After incubation, the absorbance was measured at 450 nm using a cell counting kit-8 (Cell Counting Kit-8, Dojindo Inc.) to confirm cell viability.
그 결과, 도 2에 개시된 바와 같이 상기 제조예 1의 보골지 열수 추출물(WEPC), 상기 제조예 2의 보골지 열수 추출물의 조다당 분획물(WEPC-PO) 및 조다당 제외 분획물(WEPC-ED)은 100㎍/mL 농도까지 세포 생존에 영향을 미치지 않는 안전한 물질임을 확인하였다. As a result, as shown in FIG. 2 , the bogolji hot water extract of Preparation Example 1 (WEPC), the crude polysaccharide fraction (WEPC-PO) and the crude polysaccharide exclusion fraction of the Bogolji hot water extract of Preparation Example 2 (WEPC-ED) It was confirmed that it is a safe substance that does not affect cell viability up to a concentration of 100 μg/mL.
실시예 4. 분자량에 따른 보골지 열수 추출물의 조다당 분획물 처리에 의한 파골세포 분화 억제 효과 분석(TRAP 활성도 측정)Example 4. Analysis of osteoclast differentiation inhibitory effect by treatment with crude polysaccharide fraction of Bogolji hot water extract according to molecular weight (measurement of TRAP activity)
세포 독성은 없으며, 파골세포 분화를 효과적으로 억제하는 보골지 열수 추출물의 조다당 분획물을 분자량별로 분획하여, 분자량에 따른 파골세포 분화 억제 효과를 분석하였다. 실험 방법은 상기 실시예 2에 개시된 바와 같다. There is no cytotoxicity, and the crude polysaccharide fraction of the hot water extract of Bogolji, which effectively inhibits osteoclast differentiation, was fractionated by molecular weight, and the effect of inhibiting osteoclast differentiation according to molecular weight was analyzed. The experimental method is as described in Example 2 above.
그 결과, 도 3에 개시된 바와 같이 모든 분획에서 농도의존적으로 TRAP 활성이 억제되는 것을 확인하였고, 특히, 저분자 다당이 함께 포함된 분획(3kDa Fx, 10kDa Fx)에 비해 저분자 다당이 포함되지 않은 분획(30kDa Fx, 100kDa Fx, 300kDa Fx, 1000kDa Fx)에서 TRAP 활성이 더욱 억제되는 것을 확인하였다. 또한, 300kDa Fx 및 1000kDa Fx는 저농도로 처리시 유사한 수준의 TRAP 억제 활성을 나타냈다. As a result, it was confirmed that TRAP activity was inhibited in a concentration-dependent manner in all fractions as shown in FIG. 3, and in particular, the fraction that did not contain the low molecular weight polysaccharide (3kDa Fx, 10kDa Fx) compared to the fraction containing the low molecular weight polysaccharide together (3kDa Fx, 10kDa Fx) 30kDa Fx, 100kDa Fx, 300kDa Fx, 1000kDa Fx), it was confirmed that TRAP activity was further inhibited. In addition, 300 kDa Fx and 1000 kDa Fx showed similar levels of TRAP inhibitory activity when treated at low concentrations.
실시예 5. 난소절제 마우스 골소실 모델에서의 보골지 추출물의 조다당 분획물(WEPC-PO) 투여에 의한 골소실 억제 효과 확인Example 5. Bone loss inhibitory effect confirmed by administration of the crude polysaccharide fraction (WEPC-PO) of the bogolji extract in the ovariectomized mouse bone loss model
난소 절제 마우스에 보골지 열수 추출물의 조다당 분획물(WEPC-PO)을 구강 투여한 후, 대퇴 해면골의 골밀도(BMD), 골체적(BV/TV) 및 골두께(Tb.Th) 변화를 분석하였다.After oral administration of the crude polysaccharide fraction (WEPC-PO) of the bogolji hot water extract to ovariectomized mice, changes in bone density (BMD), bone volume (BV/TV) and bone thickness (Tb.Th) of cancellous femur were analyzed. .
구체적으로, 6주령의 암컷 C57BL/6J 마우스 24마리(중앙실험동물, 서울)를 1주 순화 후, 7주령 마우스에 대하여 양측난소절제(OVX, 18마리) 수술을 하거나 가수술(Sham, 6마리)을 하였다. 1주일 후 저지방사료(D12450B, Research diet사)를 자유롭게 섭취하게 하고, 상기 양측난소절제(OVX) 마우스 중에서, 임의 선택적으로 6마리에게는 멸균 증류수에 녹인 보골지 열수 추출물의 조다당 분획물(WEPC-PO)을 마우스 kg당 30mg씩 5주 동안 매일 1회 경구 투여하였고, 다른 6마리에게는 멸균증류수에 녹인 WEPC-PO를 마우스 kg당 100mg을 5주 동안 매일 1회 경구 투여하였다. 한편, 가수술(Sham, 6마리) 군과 나머지 양측난소절제(OVX) 대조군(6마리)은 멸균증류수를 5주 동안 매일 1회 경구 투여하였다. 실험 종료 후, 대퇴골을 적출하고 10% 중성 포르말린으로 고정하였다. 대퇴골은 마이크로 컴퓨터단층촬영(micro-CT, SkyScan 1276, Bruker)하였고, 해면골(trabecular bone)의 골밀도(bone mineral density, BMD), 골체적(bone volume/total volume, BV/TV) 및 골두께(trabecular thickness, Tb.Th) 변화를 분석하였다.Specifically, after acclimatization of 24 6-week-old female C57BL/6J mice (Central Experimental Animal, Seoul) for 1 week, bilateral ovariectomy (OVX, 18 mice) or provisional surgery (Sham, 6 mice) was performed on 7-week-old mice. ) was done. After one week, a low-fat feed (D12450B, Research diet) was freely ingested, and among the bilateral ovariectomy (OVX) mice, the crude polysaccharide fraction (WEPC-PO) of bogolji hot water extract dissolved in sterile distilled water was optionally given to 6 mice ) was orally administered at 30 mg/kg per mouse once daily for 5 weeks, and to the other 6 mice, 100 mg/kg of WEPC-PO dissolved in sterile distilled water was orally administered once daily for 5 weeks. Meanwhile, the provisional surgery (Sham, 6 mice) group and the remaining bilateral ovariectomy (OVX) control group (6 mice) were orally administered with sterile distilled water once daily for 5 weeks. After completion of the experiment, the femur was removed and fixed with 10% neutral formalin. The femur was subjected to micro-computed tomography (micro-CT, SkyScan 1276, Bruker), and bone mineral density (BMD) of trabecular bone, bone volume/total volume (BV/TV) and bone thickness ( trabecular thickness, Tb.Th) changes were analyzed.
그 결과, 도 4에 개시된 바와 같이 난소절제(OVX) 대조군 대비 난소 절제를 하지 않은 가수술(Sham) 군과 보골지 열수 추출물의 조다당 분획물(WEPC-PO)을 30mg/kg 또는 100mg/kg을 투여한 군의 해면골 골밀도(BMD), 골체적(BV/TV) 및 골두께(Tb.Th)가 통계적으로 유의미하게 증가하였다. As a result, as shown in FIG. 4, the crude polysaccharide fraction (WEPC-PO) of the ovariectomized (OVX) control group and the crude polysaccharide fraction (WEPC-PO) of the bogolji hot water extract were administered at 30 mg/kg or 100 mg/kg in the ovariectomized (OVX) control group. The cancellous bone mineral density (BMD), bone volume (BV/TV), and bone thickness (Tb.Th) of the administered group were statistically significantly increased.
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