JP2010222334A - Osteoclastogenesis inhibitor - Google Patents
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本発明はヒジキの成分を含有することを特徴とした破骨細胞形成抑制組成物に関する。本発明における破骨細胞形成抑制組成物とは、骨代謝における骨吸収を抑制する事で、骨粗鬆症の予防、骨粗鬆症の進行・進展の防止、及び／又は骨粗鬆症患者における骨の状態の改善、更には骨の健康状態を維持するために、ヒト若しくはヒト以外の動物に与えられる医薬品（動物用治療薬も含む）用、飲食品用、及び飼料用の組成物を意味する。The present invention relates to an osteoclast formation inhibitory composition characterized by containing a cypress component. The composition for inhibiting osteoclast formation in the present invention suppresses bone resorption in bone metabolism, thereby preventing osteoporosis, preventing progression / progression of osteoporosis, and / or improving bone condition in osteoporosis patients, It means compositions for pharmaceuticals (including animal therapeutics), foods and drinks, and feeds given to humans or non-human animals in order to maintain bone health.
骨粗鬆症は代謝疾患、内分泌障害、加齢等により骨吸収と骨形成のバランスが崩れたために骨量が減少し、骨の粗鬆化をきたす疾病である。症状は厳しい腰背痛と骨の粗鬆化に起因する骨折を呈し、老人の場合これを契機に寝たきりとなり、生活の質を低下させ、死亡に至ることもある。抗骨粗鬆症剤としては、腰背痛の緩和作用、骨吸収抑制作用、骨形成促進作用を有する薬剤が考えられ、カルシトニン、ビタミンＤ、カルシウム剤、ビタミンＫ２、ビスホスホネート、エストロゲン、選択的エストロゲン受容体調節薬（ＳＥＲＭ）、イプリフラボンなどが使用されている。またこのうち、カルシトニン、ビスホスホネート、エストロゲンなどは、破骨細胞に直接的に作用し形成を抑制する事が知られており、破骨細胞形成抑制作用を持つ抗骨粗鬆症であるが、臨床上、薬効や副作用の点において十分に満足できる薬剤は未だなく、効果が高く副作用の少ない抗骨粗鬆症剤が望まれている。また、骨粗鬆症を予防する食品としては、大豆イソフラボン、ビタミンＫ２高産生納豆菌などが使用されている。Osteoporosis is a disease in which the bone mass decreases due to the loss of bone resorption and bone formation due to metabolic diseases, endocrine disorders, aging, and the like, resulting in bone coarsening. Symptoms include severe back pain and fractures due to bone coarsening. In the case of an elderly person, they become bedridden, which can lead to a decrease in the quality of life and death. Examples of anti-osteoporosis agents include low back pain alleviation, bone resorption suppression, and bone formation promotion, calcitonin, vitamin D, calcium, vitamin K 2 , bisphosphonate, estrogen, selective estrogen receptor Regulators (SERM), ipriflavone and the like are used. Of these, calcitonin, bisphosphonates, estrogens, etc. are known to act directly on osteoclasts and suppress their formation, and are anti-osteoporosis that has an osteoclast formation-inhibiting effect. There are still no drugs that are sufficiently satisfactory in terms of side effects and anti-osteoporosis agents that are highly effective and have few side effects. As foods for preventing osteoporosis, soy isoflavones, vitamin K2 high- producing natto bacteria, and the like are used.
ヒジキ（学名 Ｓａｒｇａｓｓｕｍ ｆｕｓｉｆｏｒｍｅ）は、ヒバマタ目ホンダワラ科ホンダワラ属の海藻の一種である。日本では、北海道南部から本州、四国、九州、南西諸島にまで分布する。春から初夏にかけて岩を覆うようにして枝部や葉部を茂らせ、枯れた後は糸状根のみが残り、春になると再び枝部、葉部をのばすという事を繰り返し、７、８年生き続ける海藻である。カルシウムやマグネシウムなどのミネラルを豊富に含むため、骨粗鬆症の予防に有用であると言われている。しかし、破骨細胞形成を抑制し、骨粗鬆症の予防に有用であるという事は報告されていない。Hijiki (scientific name Sargasssum fusiforme) is a kind of seaweed belonging to the genus Honda walla in the order of Hibamata. In Japan, it is distributed from southern Hokkaido to Honshu, Shikoku, Kyushu, and Nansei Islands. From spring to early summer, the branches and leaves are covered with rocks, and only the roots of the leaves remain after it dies. In spring, the branches and leaves are repeatedly extended and live for 7 to 8 years. Continued seaweed. Since it contains abundant minerals such as calcium and magnesium, it is said to be useful for the prevention of osteoporosis. However, it has not been reported that it suppresses osteoclast formation and is useful for prevention of osteoporosis.
本発明が解決しようとする課題は破骨細胞形成抑制作用を有する組成物を提供し、ひいては該組成物を含有する飲食品又は医薬品または飼料を提供することにある。The problem to be solved by the present invention is to provide a composition having an osteoclast formation inhibitory effect, and to provide a food, beverage, medicine or feed containing the composition.
上記課題を解決すべく研究を重ねた結果、ヒジキが破骨細胞誘導培養実験において、破骨細胞形成を抑制する事を見出した。すなわち、本発明は、以下の構成を有する。
（１）ヒジキの成分を含有することを特徴とする破骨細胞形成抑制組成物
（２）上記の成分がヒジキのメタノール抽出物である（１）に記載の破骨細胞形成抑制組成物
（３）上記（１）または（２）に記載の破骨細胞形成抑制組成物を含む飲食品または医薬品または飼料As a result of repeated studies to solve the above problems, it was found that hijiki suppresses osteoclast formation in osteoclast-induced culture experiments. That is, the present invention has the following configuration.
(1) Osteoclast formation inhibitory composition characterized by containing a hinoki component (2) The osteoclast formation inhibitory composition according to (1), wherein the above component is a hinoki methanol extract (3) ) Food / beverage products or pharmaceuticals or feed containing the osteoclast formation inhibitory composition according to (1) or (2) above
本発明により、ヒジキの成分を含有することを特徴とする破骨細胞形成抑制剤、及び該組成物を含有する飲食品または医薬品または飼料を提供することができる。ADVANTAGE OF THE INVENTION By this invention, the osteoclast formation inhibitor characterized by including the component of a hinoki, and the food-drinks or pharmaceutical or feed containing this composition can be provided.
本発明に関わる「ヒジキ」は（英名 ｈｉｊｉｋｉａ、学名 Ｓａｒｇａｓｓｕｍ ｆｕｓｉｆｏｒｍｅ）をさす。“Hijiki” related to the present invention refers to (English name hijikia, scientific name Sargassum fusiforme).
本発明に関わるヒジキは生のまま使用することができ、乾燥もしくは乾燥後粉粉砕した粉末としても使用することができる。また、熱水抽出、エタノール、または酢酸エチル等有機溶媒で抽出した抽出物としても使用できる。The hinoki involved in the present invention can be used as it is, and can also be used as a powder that is dried or pulverized after drying. It can also be used as an extract extracted with an organic solvent such as hot water extraction, ethanol, or ethyl acetate.
本発明に関わる破骨細胞形成抑制剤を製造するには、上記の方法で製造したヒジキ粉末もしくは抽出物を用いることができ、常法に従って公知の医薬用無毒性担保と組み合わせて製剤化すればよい。本発明に関わる破骨細胞形成抑制剤は、種々の剤型での投与が可能であり、例えば、経口投与剤としては錠剤、顆粒剤、散剤、カプセル剤、ソフトカプセル剤等の固形剤、溶液剤、懸濁剤、乳剤等の液剤、凍結乾燥製剤等が挙げられ、非経口投与剤としては、注射剤のほか、坐剤、噴射剤、経皮吸収剤等が挙げられ、これらの製剤は製剤上の常套手段により調整することができる。上記の医薬用無毒性担保としては、例えば、グルコース、乳糖、ショ糖、澱粉、マンニトール、デキストリン、脂肪酸グリセリド、ポリエチレングリコール、ヒドロキシエチルデンプン、エチレングリコール、ポリオキシエチレンソルビタン脂肪酸エステル、アミノ酸、アルブミン、水、生理食塩水等が挙げられる。また、必要に応じて安定化剤、滑剤、湿潤剤、乳化剤、結合剤等の慣用の添加剤を適宜添加することができる。本発明に関わる破骨細胞形成抑制剤においてヒジキ粉末もしくは抽出物の投与量は、患者の年齢、体重、症状、疾患の程度、投与スケジュール、製剤形態などにより、適宜選択・決定されるが、例えば、一日当たり０．０１〜１０ｇ／体重程度とされ、一日数回に分けて投与してもよい。
動物においても同様に製剤化すればよい。動物の年齢、体重、症状、疾患の程度、投与スケジュール、製剤形態などにより、適宜選択・決定されるが、例えば、一日あたり０．０１〜１０ｇ／ｋｇ体重程度とされ、一日数回に分けて投与してもよい。In order to produce the osteoclast formation inhibitor according to the present invention, the pheasant powder or extract produced by the above method can be used, and if formulated in combination with a known non-toxic medicinal collateral according to a conventional method Good. The osteoclast formation inhibitor according to the present invention can be administered in various dosage forms. For example, as oral administration agents, solid agents such as tablets, granules, powders, capsules, soft capsules, and solutions Liquids such as suspensions and emulsions, lyophilized preparations, and the like, and parenteral administration agents include injections, suppositories, propellants, transdermal absorption agents, and the like. Adjustments can be made by conventional means above. Examples of the non-toxic collateral for pharmaceutical use include glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, albumin, water And physiological saline. In addition, conventional additives such as stabilizers, lubricants, wetting agents, emulsifiers, binders and the like can be appropriately added as necessary. In the osteoclast formation inhibitor according to the present invention, the dosage of HIKIKI powder or extract is appropriately selected and determined according to the patient's age, weight, symptoms, degree of disease, administration schedule, formulation form, etc. The dose may be about 0.01 to 10 g / body weight per day, and may be divided into several times a day.
A similar formulation may be used for animals. It is appropriately selected and determined according to the age, body weight, symptoms, degree of disease, administration schedule, formulation form, etc. of the animal. For example, it is about 0.01 to 10 g / kg body weight per day and divided into several times a day. May be administered.
また、本発明に関わるヒジキは、食経験も豊富なことから安全性が高いと考えられ、破骨細胞形成抑制を目的として、機能性食品としても摂取することができる。本発明に関わるヒジキの成分を含有することを特徴とする機能性食品は、特定保健用食品、栄養機能性食品、又は健康食品として位置づけることができる。機能性食品としては、例えば、ヒジキの抽出物に適当な助剤を添加した後、慣用の手段を用いて、食用に適した形態、例えば、顆粒状、粒状、錠剤、カプセル剤、ペースト状等に形成したものを用いることができる。この機能性食品はそのまま食用に供してもよく、また種々の食品、例えばハム、ソーセージ、かまぼこ、ちくわ、パン、バター、粉乳、菓子などに添加して使用したり、水、酒類、果汁、牛乳、清凉飲料水等の飲物に添加して使用したりしてもよい。かかる食品の形態における本発明のヒジキの成分摂取量は、対象の年齢、体重、症状、摂取スケジュール、製剤形態などにより、適宜選択・決定されるが、例えば、一日当たり０．０１〜１０ｇ／ｋｇ体重程度とされる。
動物においても同様に、例えばヒジキの抽出物に適当な助剤を添加した後、慣用の手段を用いて、食用に適した形態、顆粒状、粒状、錠剤、カプセル剤、ペースト状等に形成したものを用いることができる。また、飼料およびペットフードに添加して使用したり、水などの飲料水に添加してもよい。かかる食品の形態における本発明のヒジキの成分摂取量は、動物の年齢、体重、症状、摂取スケジュール、製剤形態などにより、適宜選択・決定されるが、例えば、一日当たり０．０１〜１０ｇ／ｋｇ体重程度とされる。Moreover, the hinoki involved in the present invention is considered to be highly safe because of its rich dietary experience, and can be taken as a functional food for the purpose of inhibiting osteoclast formation. The functional food characterized by containing a cypress component related to the present invention can be positioned as a food for specified health use, a nutritional functional food, or a health food. As a functional food, for example, after adding a suitable auxiliary agent to the extract of hinoki, using a conventional means, a form suitable for consumption, for example, granular, granular, tablet, capsule, paste, etc. What was formed in can be used. This functional food may be used for food as it is, and used by adding it to various foods such as ham, sausage, kamaboko, chikuwa, bread, butter, powdered milk, confectionery, etc., water, liquor, fruit juice, milk It may be used by adding to drinks such as neat drinking water. Ingredient intake of the hinoki of the present invention in the form of such food is appropriately selected and determined according to the age, weight, symptoms, intake schedule, formulation form, etc. of the subject. For example, 0.01-10 g / kg per day It is considered to be about body weight.
Similarly, in animals, for example, after adding a suitable auxiliary agent to the extract of hinoki, it is formed into an edible form, granules, granules, tablets, capsules, pastes, etc. using conventional means. Things can be used. Moreover, you may add and use for feed and pet food, or may add to drinking water, such as water. The ingredient intake of the hinoki of the present invention in the form of such food is appropriately selected and determined according to the age, weight, symptoms, intake schedule, formulation form, etc. of the animal. For example, 0.01-10 g / kg per day It is considered to be about body weight.
以下に本発明をより詳細に説明する為に実施例を挙げるが、本発明はこれらによって何ら限定されるものではない。Examples are given below to describe the present invention in more detail, but the present invention is not limited by these.
実施例 ヒジキの破骨細胞形成抑制効果
骨において破骨細胞は骨吸収を行い、骨組織を溶かす働きを担っている。骨髄細胞中の造血幹細胞や単球が、様々なサイトカイン等や骨芽細胞より発現される因子により融合・多核化する事により、破骨細胞形成及び活性化が起こる。この破骨細胞形成を再現した骨髄細胞培養実験において、破骨細胞が発現するＴＲＡＰ（酒石酸ホスファターゼ）を染色する事で、破骨細胞形成数が骨吸収能のパラメータの一つとして評価される。
そこで、マウスより採取した骨髄細胞と株化骨芽細胞を混合し、これを破骨細胞誘導因子であるＰＧＥ２およびビタミンＤ３を添加した培地にて培養する事で、破骨細胞形成を誘導し、ヒジキ抽出物添加、無添加での破骨細胞形成数の違いを試験した。
ヒジキ無添加の対照群の破骨細胞形成数を１００とし、ヒジキ添加群の破骨細胞形成数を平均値±標準誤差の百分率で示した。
各群の対照群に対する有意差の検定は、Ｓｔｕｄｅｎｔ‘ｓ ｔ−ｔｅｓｔにより行った。
対照群と比較して危険率５．０％、１．０％、０．５％で有意差があった場合、それぞれ＃、＃＃、＃＃＃で示した。Example Inhibition of osteoclast formation by cypress Osteoclasts resorb bone and dissolve bone tissue in bone. Osteoclast formation and activation occur when hematopoietic stem cells and monocytes in bone marrow cells are fused and multinucleated by various cytokines and factors expressed from osteoblasts. In bone marrow cell culture experiments that reproduce this osteoclast formation, the number of osteoclast formation is evaluated as one of the parameters of bone resorption ability by staining TRAP (tartrate phosphatase) expressed by osteoclasts.
Therefore, osteoclast formation is induced by mixing bone marrow cells collected from mice and established osteoblasts and culturing them in a medium supplemented with PGE 2 and vitamin D 3 as osteoclast-inducing factors. Then, the difference in the number of osteoclasts formed with and without the addition of the hinoki extract was tested.
The number of osteoclasts formed in the control group to which no hinoki was added was defined as 100, and the number of osteoclasts formed in the group to which hinoki was added was expressed as a percentage of the average value ± standard error.
The test of the significant difference of each group with respect to the control group was performed by Student's t-test.
When there was a significant difference in the risk rates of 5.0%, 1.0%, and 0.5% compared to the control group, they were indicated by #, ##, and ##, respectively.
表に示した結果から、ヒジキメタノール抽出物が破骨細胞形成抑制に有効であることが判明した。From the results shown in the table, it was found that the hijimethanol extract was effective in inhibiting osteoclast formation.
本発明により、ヒジキの成分を含有することを特徴とする破骨細胞形成抑制組成物及び該組成物を含有する飲食品又は医薬品または飼料を提供することが可能となった。According to the present invention, it is possible to provide an osteoclast formation inhibitory composition characterized by containing a cypress component, and a food or drink, a pharmaceutical product or a feed containing the composition.
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Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009098441A JP2010222334A (en) | 2009-03-24 | 2009-03-24 | Osteoclastogenesis inhibitor |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009098441A JP2010222334A (en) | 2009-03-24 | 2009-03-24 | Osteoclastogenesis inhibitor |
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| JP2010222334A true JP2010222334A (en) | 2010-10-07 |
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