JP2001158736A - Agent for preventing and improving osteoarthropathy - Google Patents
Agent for preventing and improving osteoarthropathyInfo
- Publication number
- JP2001158736A JP2001158736A JP34021199A JP34021199A JP2001158736A JP 2001158736 A JP2001158736 A JP 2001158736A JP 34021199 A JP34021199 A JP 34021199A JP 34021199 A JP34021199 A JP 34021199A JP 2001158736 A JP2001158736 A JP 2001158736A
- Authority
- JP
- Japan
- Prior art keywords
- fraction
- vitamin
- ganglioside
- calcium
- preventing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 108010005965 endoglycoceramidase Proteins 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 235000013310 margarine Nutrition 0.000 description 1
- 239000003264 margarine Substances 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000009806 oophorectomy Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 235000020185 raw untreated milk Nutrition 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000004455 soybean meal Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical class C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、スフィンゴシン骨
格を有する化合物を有効成分とする骨関節疾患の予防及
び改善剤に関する。また、本発明は、スフィンゴシン骨
格を有する化合物を配合して骨関節疾患の予防及び改善
効果を賦与した飲食品又は飼料に関する。TECHNICAL FIELD The present invention relates to a preventive and ameliorating agent for osteoarticular diseases comprising a compound having a sphingosine skeleton as an active ingredient. In addition, the present invention relates to a food or drink or feed which has a compound having a sphingosine skeleton and which has an effect of preventing and improving osteoarthritis.
【０００２】[0002]
【従来の技術】近年、高齢化に伴い、骨粗鬆症、骨折、
腰痛及びリウマチなどの骨関節疾患が増加している。骨
組織においては、絶えず骨形成と骨吸収が営まれてお
り、若い時には骨形成と骨吸収のバランスがとれている
が、加齢に伴い種々の原因からそのバランスが骨吸収に
傾いてくる。そして、この状態が長期間続くと骨組織が
脆くなり、骨粗鬆症、骨折及び腰痛などの骨関節疾患を
生じることになる。このアンカップリングを防ぐことが
できれば、骨粗鬆症、骨折及び腰痛などの骨関節疾患を
予防できると考えられている。また、リウマチは、炎症
から最終的に骨吸収を伴う疾患であることから、骨吸収
を抑制することでリウマチを予防及び改善することがで
きると考えられている。2. Description of the Related Art In recent years, with aging, osteoporosis, fracture,
Bone and joint diseases such as back pain and rheumatism are increasing. In bone tissue, bone formation and bone resorption are constantly performed, and at a young age, the balance between bone formation and bone resorption is maintained. However, with aging, the balance tends to bone resorption from various causes. If this state continues for a long period of time, the bone tissue becomes brittle, resulting in osteoarthritis such as osteoporosis, fracture and back pain. It is considered that if this uncoupling can be prevented, osteoarthritis such as osteoporosis, fracture and back pain can be prevented. Moreover, since rheumatism is a disease that is finally accompanied by bone resorption from inflammation, it is considered that rheumatism can be prevented and improved by suppressing bone resorption.
【０００３】従来より、アンカップリングを防ぎ、各種
骨関節疾患を予防及び改善する方法として、(1) 食事に
よるカルシウムの補給、(2) 軽い運動、(3) 日光浴、
(4) 薬物治療などが行われている。１の食事によるカル
シウムの補給には、通常、炭酸カルシウム、リン酸カル
シウムなどのカルシウム塩や牛骨粉、卵殻、魚骨粉など
の天然カルシウム剤が使用されている。２の軽い運動に
ついては、軽いランニングや散歩などが良いとされる
が、体が弱っていると軽い運動もやっかいなものとな
り、まして寝たきりの老人になると殆ど運動することは
できない。また、３の日光浴は、活性化ビタミンＤ3 の
補給を補完するという点では良いとされているが、各種
骨関節疾患に関わる問題全般を解決できるわけではな
い。さらに、４の薬物治療としては、１α−ヒドロキシ
ビタミンＤ3 、カルシトニン製剤などが骨粗鬆症の治療
及び改善に有効であることが知られている。しかし、カ
ルシトニン製剤は医薬品としてのホルモン製剤であり、
食品素材のように毎日摂取することができ、かつ安全な
各種骨関節疾患を予防及び改善する物質については検討
されていないのが現状である。Conventionally, methods for preventing uncoupling and preventing and ameliorating various osteoarticular diseases include (1) dietary calcium supplementation, (2) light exercise, (3) sunbathing,
(4) Drug treatment is performed. For the supplementation of calcium by one meal, calcium salts such as calcium carbonate and calcium phosphate and natural calcium agents such as bovine bone meal, eggshell and fish bone powder are usually used. For light exercise, light running and walking are considered to be good, but light exercise is awkward if your body is weak, and you can hardly exercise when you are a bedridden elderly person. Also, sunbathing of 3 is good in that it supplements the supplementation of activated vitamin D3, but it cannot solve all problems related to various osteoarticular diseases. Furthermore, it is known that 1α-hydroxyvitamin D 3 , a calcitonin preparation, and the like are effective for the treatment and improvement of osteoporosis as the drug treatment of 4. However, calcitonin preparations are hormone preparations as pharmaceuticals,
At present, there is no study on substances that can be taken daily and that can safely prevent and improve various osteoarticular diseases, such as food materials.
【０００４】[0004]
【発明が解決しようとする課題】上記するように、骨粗
鬆症、骨折、腰痛及びリウマチなどの骨関節疾患は大き
な社会問題になっており、これらの症状を予防及び改善
する方法が求められている。本発明者らは、各種骨関節
疾患の予防及び改善効果を有する物質を得るべく鋭意研
究を進めてきたところ、牛乳や牛脳中に含まれるセラミ
ド、スフィンゴミエリン、スフィンゴ糖脂質、ガングリ
オシドなどのスフィンゴシン骨格を有する化合物に各種
骨関節疾患を予防及び改善する効果があることを見出し
た。そして、カルシウム剤、ビタミンＤ、ビタミンＫを
加えることによりその効果が高まることを見出し、本発
明を完成するに至った。したがって、本発明は、スフィ
ンゴシン骨格を有する化合物を有効成分とする骨関節疾
患の予防及び改善剤を提供すること、及びカルシウム
剤、ビタミンＤ及びビタミンＫから選ばれる一種以上の
物質を加えた上記の骨関節疾患の予防及び改善剤を提供
することを課題とする。また、本発明は、スフィンゴシ
ン骨格を有する化合物を配合して骨関節疾患の予防及び
改善効果を賦与した飲食品又は飼料を提供すること、及
びカルシウム剤、ビタミンＤ及びビタミンＫから選ばれ
る一種以上の物質を加えた上記の飲食品又は飼料を提供
することを課題とする。As described above, osteoarthritis such as osteoporosis, fracture, low back pain and rheumatism has become a major social problem, and there is a need for a method for preventing and improving these symptoms. The present inventors have intensively studied to obtain a substance having a preventive and ameliorating effect on various osteoarticular diseases, and found that sphingosine such as ceramide, sphingomyelin, glycosphingolipid, and ganglioside contained in milk and bovine brain. It has been found that compounds having a skeleton have an effect of preventing and improving various osteoarticular diseases. Then, they found that the effect was enhanced by adding a calcium agent, vitamin D, and vitamin K, and completed the present invention. Therefore, the present invention provides a preventive and ameliorating agent for osteoarthritis comprising a compound having a sphingosine skeleton as an active ingredient, and a calcium agent, vitamin D and vitamin K, and It is an object to provide an agent for preventing and improving osteoarthritis. Further, the present invention provides a food or drink or feed which has a compound having a sphingosine skeleton and which has the effect of preventing and ameliorating osteoarthritis, and a calcium agent, vitamin D and vitamin K. An object of the present invention is to provide the above-mentioned food or drink or feed to which a substance is added.
【０００５】[0005]
【課題を解決するための手段】本発明では、セラミド、
スフィンゴミエリン、スフィンゴ糖脂質、ガングリオシ
ドなどのスフィンゴシン骨格を有する化合物を骨関節疾
患の予防及び改善剤の有効成分として使用する。また、
本発明では、セラミド、スフィンゴミエリン、スフィン
ゴ糖脂質、ガングリオシドなどのスフィンゴシン骨格を
有する化合物を飲食品や飼料に配合して骨関節疾患の予
防及び改善効果を賦与する。スフィンゴシンは、スフィ
ンゴ脂質を構成する長鎖塩基の１種であり、生体中に広
く分布している。スフィンゴシンは、生体内で、脂肪酸
と酸アミド結合してセラミドを構成し、スフィンゴ脂質
の骨格を成している。According to the present invention, ceramide,
A compound having a sphingosine skeleton such as sphingomyelin, glycosphingolipid, and ganglioside is used as an active ingredient of an agent for preventing and improving osteoarthritis. Also,
In the present invention, a compound having a sphingosine skeleton, such as ceramide, sphingomyelin, glycosphingolipid, and ganglioside, is added to foods and drinks and feeds to provide the effect of preventing and improving osteoarthritis. Sphingosine is one of the long-chain bases constituting sphingolipids, and is widely distributed in living organisms. Sphingosine forms a ceramide by binding an acid amide with a fatty acid in a living body, and forms a sphingolipid skeleton.
【０００６】スフィンゴ脂質は、細胞膜を構成する成分
であり、その大部分がスフィンゴ糖脂質やスフィンゴリ
ン脂質として存在している。スフィンゴ脂質は、脳や神
経系又は赤血球に多く含まれている。また、種々の食品
中にも含まれているが、特に牛乳中に多く含まれてい
る。スフィンゴ脂質の生理作用に関しては、非常に多く
の報告がこれまでになされてきている。例えば、スフィ
ンゴシン蛋白質リン酸化酵素Ｃを阻害すること、単球や
マクロファージ系細胞の分化を促進する作用を有するこ
と、上皮細胞成長因子（ＥＧＦ）レセプターの機能を調
節する作用を有することなどである。また、スフィンゴ
脂質の中でも、ガングリオシドは、脳虚血障害やパーキ
ンソン病による脳障害の治療にも応用されている。[0006] Sphingolipids are components constituting cell membranes, and most of them are present as glycosphingolipids and sphingolipids. Sphingolipids are abundant in the brain, nervous system or red blood cells. It is also contained in various foods, but especially in milk. Numerous reports have been made on the physiological actions of sphingolipids. For example, they inhibit sphingosine protein kinase C, have an action to promote the differentiation of monocytes and macrophage cells, and have an action to regulate the function of epidermal growth factor (EGF) receptor. Among sphingolipids, gangliosides have also been applied to the treatment of cerebral ischemia disorders and brain disorders due to Parkinson's disease.
【０００７】スフィンゴシン骨格を有する化合物のセラ
ミド、スフィンゴミエリン、スフィンゴ糖脂質、ガング
リオシドなどの化合物は、化成品や動植物由来のものを
使用すれば良い。そして、これらの化合物は、牛乳や牛
脳などに含まれているので、生乳、粉乳、脱脂乳、還元
乳などの牛乳や牛脳を原料とし、加熱、加塩、アルコー
ル添加、イオン交換クロマトグラフィーやゲル濾過クロ
マトグラフィーなどの各種クロマトグラフィー、限外濾
過（ＵＦ）などの処理を行うことにより得ることができ
る。なお、スフィンゴシン骨格を有する化合物は熱安定
性を有するので、特に飲食品や飼料などに配合する際に
極めて取扱いし易い。また、本発明では、上記したスフ
ィンゴシン骨格を有する化合物を有効成分とする骨関節
疾患の予防及び改善剤の効果を高めるために、カルシウ
ム剤、ビタミンＤ及びビタミンＫから選ばれる一種以上
の物質を加える。また、本発明では、上記したスフィン
ゴシン骨格を有する化合物を配合して骨関節疾患の予防
及び改善効果を賦与した飲食品や飼料の効果を高めるた
めに、カルシウム剤、ビタミンＤ及びビタミンＫから選
ばれる一種以上の物質を加える。本発明で使用するカル
シウム剤としては、例えば、塩化カルシウム、炭酸カル
シウム、乳酸カルシウムなどのカルシウム塩、卵殻、あ
るいは牛乳由来のカルシウム含有組成物などを挙げるこ
とができるが、吸収性の良いカルシウム塩を使用するこ
とが望ましい。また、ビタミンＤやビタミンＫなどの骨
に有効な成分を配合することが望ましい。このようなカ
ルシウム剤やビタミン類は、スフィンゴシン骨格を有す
る化合物と作用機作が異なり、骨に対して相乗的に効果
を示す。Compounds having a sphingosine skeleton, such as ceramide, sphingomyelin, glycosphingolipids, and gangliosides, may be those derived from chemical products and animals and plants. And since these compounds are contained in milk and cow brain, raw milk, milk powder, skim milk, reduced milk and other milk and cow brain are used as raw materials, heating, salt addition, alcohol addition, ion exchange chromatography and It can be obtained by performing various kinds of chromatography such as gel filtration chromatography and processing such as ultrafiltration (UF). Since the compound having a sphingosine skeleton has heat stability, it is extremely easy to handle, especially when blended in foods and drinks and feeds. Further, in the present invention, in order to enhance the effect of the preventive and ameliorating agent for osteoarthritis containing the compound having a sphingosine skeleton as an active ingredient, one or more substances selected from calcium, vitamin D and vitamin K are added. . In the present invention, the compound having a sphingosine skeleton described above is selected from calcium, vitamin D, and vitamin K in order to enhance the effects of foods and drinks and feeds that have the effect of preventing and improving osteoarthritis by adding the compound having a sphingosine skeleton. Add one or more substances. Examples of the calcium agent used in the present invention include, for example, calcium chloride, calcium carbonate, calcium salts such as calcium lactate, eggshell, or a calcium-containing composition derived from milk. It is desirable to use. In addition, it is desirable to mix ingredients effective for bone, such as vitamin D and vitamin K. Such calcium agents and vitamins have a different mechanism of action from compounds having a sphingosine skeleton, and exhibit a synergistic effect on bone.
【０００８】[0008]
【発明の実施の形態】本発明においては、化成品、ある
いは牛乳や牛脳由来のスフィンゴシン骨格を有するセラ
ミド、スフィンゴミエリン、スフィンゴ糖脂質、ガング
リオシドなどの化合物を有効成分として、骨関節疾患の
予防及び改善剤を調製し、さらに、カルシウム剤、ビタ
ミンＤ及びビタミンＫから選ばれる一種以上の物質を加
えて、骨関節疾患の予防及び改善剤を調製する。また、
本発明においては、化成品、あるいは牛乳や牛脳由来の
スフィンゴシン骨格を有するセラミド、スフィンゴミエ
リン、スフィンゴ糖脂質、ガングリオシドなどの化合物
を配合して骨関節疾患の予防及び改善効果を賦与した飲
食品又は飼料を調製し、さらに、カルシウム剤、ビタミ
ンＤ及びビタミンＫから選ばれる一種以上の物質を加え
て、骨関節疾患の予防及び改善効果を賦与した飲食品又
は飼料を調製する。BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, a compound such as a ceramide, sphingomyelin, glycosphingolipid, or ganglioside having a sphingosine skeleton derived from milk or bovine brain is used as an active ingredient to prevent osteoarticular diseases. An ameliorating agent is prepared, and one or more substances selected from calcium, vitamin D and vitamin K are added to prepare a osteoarthritis preventing and ameliorating agent. Also,
In the present invention, a food or drink which imparts a preventive and ameliorating effect on osteoarticular diseases by compounding a compound such as a ceramide having a sphingosine skeleton derived from a chemical product or milk or bovine brain, sphingomyelin, glycosphingolipid, ganglioside, or A feed is prepared, and further, one or more substances selected from calcium agents, vitamin D and vitamin K are added to prepare a food or drink or a feed that has the effect of preventing and improving osteoarthritis.
【０００９】本発明においては、スフィンゴシン骨格を
有する化合物を成人一人一日当たり１μg 〜10mgを数回
に分けて摂取することにより、骨粗鬆症、骨折、腰痛及
びリウマチなどの骨関節疾患を予防及び改善することが
できる。したがって、それらの量を摂取することができ
るように、スフィンゴシン骨格を有する化合物を飲食品
や飼料に配合すれば良い。さらに、カルシウム剤、ビタ
ミンＤ及びビタミンＫから選ばれる一種以上の物質を適
当量加えることにより、骨関節疾患の予防及び改善効果
を高めることができる。なお、飲食品としては、例え
ば、牛乳、乳飲料、ジュース、ゼリー、ビスケット、パ
ン、麺、ソーセージなどを挙げることができる。次に、
実施例及び試験例を示し、本発明を詳細に説明する。According to the present invention, a compound having a sphingosine skeleton is taken in an amount of 1 μg to 10 mg per adult per day in several divided doses to prevent and ameliorate osteoarticular diseases such as osteoporosis, fractures, back pain and rheumatism. Can be. Therefore, a compound having a sphingosine skeleton may be added to foods and drinks and feeds so that those amounts can be ingested. Furthermore, by adding an appropriate amount of one or more substances selected from calcium agents, vitamin D and vitamin K, the effect of preventing and improving osteoarthritis can be enhanced. In addition, as foods and drinks, for example, milk, milk drink, juice, jelly, biscuit, bread, noodle, sausage and the like can be mentioned. next,
The present invention will be described in detail with reference to Examples and Test Examples.
【００１０】[0010]
【参考例１】牛乳由来のガングリオシドの調製；公知の
ガングリオシド調製法 (特開昭 63-369992号公報) に従
い、牛乳由来のガングリオシドを調製した。すなわち、
ガングリオシドを含む乳質物質に蛋白質分解酵素のトリ
プシンを40℃で15時間作用させて蛋白質を分解した後、
得られた蛋白質分解物溶液を分子量分画10,000の膜で透
析して、ガングリオシド高含有画分を得た。このガング
リオシド高含有画分を凍結乾燥した後、クロロホルム−
メタノール（１：１）溶液に溶解し、この溶液を陰イオ
ン交換樹脂(DEAE-Sephadexアセテート型、ファルマシア
社製）に通液して、ガングリオシドを吸着させた。次
に、陰イオン交換樹脂をクロロホルム−メタノール
（１：１）溶液で洗浄した後、0.1M酢酸ナトリウム水溶
液−メタノ−ル溶液でガングリオシドを溶出した。そし
て、溶出液を減圧乾固した後、透析して脱塩し、凍結乾
燥した。このようにして得られたガングリオシド画分
（画分Ａ）を薄層クロマトグラフィー（レゾルシノール
法）で検出したところ、ガングリオシドＧＭ３：ガング
リオシドＧＤ３：ガングリオシドＧＴ３＝10：90：１で
あった。さらに、画分Ａを分画した。すなわち、クロロ
ホルム−メタノール (８：８(v/v))溶液に画分Ａを懸濁
し、シリカゲル（イアトロビーズ、iatron laboratory
社製）カラムに添加して、８：２(v/v) から２：８(v/
v) までのクロロホルム−メタノール溶液でグラジエン
ト溶出し、ガングリオシドＧＭ３画分（画分Ｂ）、ガン
グリオシドＧＤ３画分（画分Ｃ）及びガングリオシドＧ
Ｔ３画分（画分Ｄ）に分画した。このようにして得られ
た各ガングリオシド画分を薄層クロマトグラフィー（レ
ゾルシノール法）で検出したところ、純度は95％以上で
あった。Reference Example 1 Preparation of milk-derived gangliosides: Milk-derived gangliosides were prepared according to a known ganglioside preparation method (JP-A-63-369992). That is,
After a proteinase trypsin is allowed to act on milk substances containing ganglioside at 40 ° C for 15 hours to degrade the protein,
The obtained protein hydrolyzate solution was dialyzed with a membrane having a molecular weight cutoff of 10,000 to obtain a ganglioside-rich fraction. After freeze-drying the ganglioside-rich fraction, chloroform-
It was dissolved in a methanol (1: 1) solution, and this solution was passed through an anion exchange resin (DEAE-Sephadex acetate type, manufactured by Pharmacia) to adsorb ganglioside. Next, the anion exchange resin was washed with a chloroform-methanol (1: 1) solution, and then ganglioside was eluted with a 0.1 M sodium acetate aqueous solution-methanol solution. The eluate was dried under reduced pressure, dialyzed, desalted, and freeze-dried. When the ganglioside fraction (fraction A) thus obtained was detected by thin-layer chromatography (resorcinol method), ganglioside GM3: ganglioside GD3: ganglioside GT3 = 10: 90: 1. Further, fraction A was fractionated. That is, the fraction A was suspended in a chloroform-methanol (8: 8 (v / v)) solution, and silica gel (Iatrobeads, iatron laboratory, iatron laboratory) was used.
8: 2 (v / v) to 2: 8 (v / v)
gradient elution with a chloroform-methanol solution up to v), ganglioside GM3 fraction (fraction B), ganglioside GD3 fraction (fraction C) and ganglioside G
It was fractionated into T3 fraction (fraction D). When each ganglioside fraction thus obtained was detected by thin-layer chromatography (resorcinol method), the purity was 95% or more.
【００１１】[0011]
【参考例２】牛脳由来のガングリオシドの調製；一般に
広く行われているガングリオシド調製法に従い、牛脳由
来のガングリオシドを調製した。すなわち、屠殺直後に
摘出し、−20℃で保存しておいた牛脳５kgを凍結乾燥し
た後、ミキサーで粗い粉末とし、メタノール 10 l を加
えて60℃に加熱して30分放置し、ガングリオシドを含む
画分を抽出し、抽出後、直ぐに吸引濾過して得られた濾
液を−10℃で一晩放置した。そして、生成した沈澱を手
早く吸引濾過して回収し、 Folch分配した後、その上層
を減圧濃縮し、凍結乾燥した。このようにして得られた
画分をシリカゲルカラムクロマトグラフィーで処理し
て、中性脂質及びスルファチドを分離し、ガングリオシ
ド画分（画分Ｅ）4.87g を得た。このようにして得られ
た画分Ｅには、ガングリオシドＧＤ1a、ガングリオシド
ＧＭ１、ガングリオシドＧＤ1b、ガングリオシドＧＴ1b
などが含まれていた。さらに、画分Ｅを分画した。すな
わち、Q-Sepharose カラムに、クロロホルム−メタノー
ル−水（30：60：８）溶液 500mlに溶解した画分Ｅを添
加して、クロロホルム−メタノール−水（30：60：８）
溶液 3 lからクロロホルム−メタノール−4M酢酸ナトリ
ウム水溶液（30：60：８）溶液 3 lまででグラジエント
溶出し、ガングリオシドＧＤ1a（画分Ｆ)1,220mg、ガン
グリオシドＧＭ１ (画分Ｇ)102mg、ガングリオシドＧＤ
1b (画分Ｈ)451mg、ガングリオシドＧＴ1b (画分Ｉ)540
mgを得た。Reference Example 2 Preparation of Bovine Brain-Derived Ganglioside: Bovine brain-derived ganglioside was prepared according to a generally widely used ganglioside preparation method. That is, 5 kg of bovine brain, which was removed immediately after slaughter and stored at -20 ° C, was freeze-dried, turned into a coarse powder with a mixer, added with 10 l of methanol, heated to 60 ° C, and left for 30 minutes to form ganglioside. Was extracted, and immediately after the extraction, the filtrate obtained by suction filtration was allowed to stand at −10 ° C. overnight. The resulting precipitate was quickly collected by suction filtration, and after Folch distribution, the upper layer was concentrated under reduced pressure and freeze-dried. The fraction thus obtained was subjected to silica gel column chromatography to separate neutral lipid and sulfatide, thereby obtaining 4.87 g of a ganglioside fraction (fraction E). The fraction E thus obtained contains ganglioside GD1a, ganglioside GM1, ganglioside GD1b, ganglioside GT1b.
And so on. Further, fraction E was fractionated. That is, a fraction E dissolved in 500 ml of a chloroform-methanol-water (30: 60: 8) solution was added to a Q-Sepharose column, and chloroform-methanol-water (30: 60: 8) was added.
Gradient elution was performed from 3 l of the solution to 3 l of a chloroform-methanol-4 M aqueous sodium acetate solution (30: 60: 8), and 1,220 mg of ganglioside GD1a (fraction F), 102 mg of ganglioside GM1 (fraction G), and ganglioside GD.
1b (Fraction H) 451 mg, Ganglioside GT1b (Fraction I) 540
mg was obtained.
【００１２】[0012]
【参考例３】牛乳由来のスフィンゴミエリンの調製；牛
乳からスフィンゴミエリンを調製した。すなわち、バタ
ーオイルを製造する際に排出されるバターセーラム10kg
を凍結乾燥した後、これを60℃でメタノール90 l に溶
解した。室温で12時間放置した後、生成した沈澱が混入
しないように上清を回収し、減圧濃縮してメタノールを
除去した。得られた固形物を脱イオン水 10 l に溶解し
た後、限外濾過して低分子画分を除去し、凍結乾燥して
高分子画分を得た。この高分子画分は600gであり、この
高分子画分に含まれるスフィンゴミエリン含量は15.2％
であった。さらに、スフィンゴミエリンを精製するため
に、シリカゲルカラムクロマトグラフィーで精製した。
すなわち、シリカゲルカラム 10 l に、スフィンゴミエ
リンを含む高分子画分500gを溶解したクロロホルム：メ
タノール（９：１）溶液を添加した。そして、メタノー
ル濃度を高めてグラジエント溶出し、スフィンゴミエリ
ン画分（画分Ｊ）37.3ｇを得た。このようにして得られ
たスフィンゴミエリン画分は純度98％以上であった。Reference Example 3 Preparation of sphingomyelin derived from milk; sphingomyelin was prepared from milk. In other words, 10 kg of butter salem discharged when manufacturing butter oil
After freeze-drying, it was dissolved at 60 ° C. in 90 l of methanol. After allowing to stand at room temperature for 12 hours, the supernatant was recovered so that the formed precipitate was not mixed, and concentrated under reduced pressure to remove methanol. The obtained solid was dissolved in 10 l of deionized water, ultrafiltered to remove the low molecular weight fraction, and lyophilized to obtain a high molecular weight fraction. The polymer fraction was 600 g, and the sphingomyelin content in the polymer fraction was 15.2%.
Met. Further, in order to purify sphingomyelin, it was purified by silica gel column chromatography.
That is, a chloroform: methanol (9: 1) solution in which 500 g of a polymer fraction containing sphingomyelin was dissolved was added to 10 l of a silica gel column. Then, the methanol concentration was increased and gradient elution was performed to obtain 37.3 g of a sphingomyelin fraction (fraction J). The sphingomyelin fraction thus obtained had a purity of 98% or more.
【００１３】[0013]
【参考例４】牛乳由来のセラミドの調製；参考例１で得
られたガングリオシド画分（画分Ａ）からセラミドを調
製した。すなわち、酢酸緩衝液(pH 5.5)中で、画分Ａ 2
0gに対して Endoglycoceramidase(宝酒造社製）500Uを
添加し、12時間反応させた。反応後、反応液をＦolch分
配して脂質画分を回収し、陰イオン交換樹脂カラムクロ
マトグラフィーで糖脂質を除去した。そして、オクタデ
シルシリルカラムクロマトグラフィーでセラミド部分を
精製し、窒素を吹き付け乾固させた。このようにして、
セラミド画分（画分Ｋ）6gを得た。このセラミド画分は
純度98％以上であった。Reference Example 4 Preparation of ceramide derived from milk; Ceramide was prepared from the ganglioside fraction (fraction A) obtained in Reference Example 1. That is, in an acetate buffer (pH 5.5), fraction A 2
To 0 g, 500 U of Endoglycoceramidase (Takara Shuzo) was added and reacted for 12 hours. After the reaction, the reaction solution was partitioned by Folch to collect a lipid fraction, and glycolipids were removed by anion exchange resin column chromatography. Then, the ceramide portion was purified by octadecylsilyl column chromatography, and nitrogen was blown to dryness. In this way,
6 g of a ceramide fraction (fraction K) was obtained. This ceramide fraction had a purity of 98% or more.
【００１４】[0014]
【試験例１】スフィンゴシン骨格を有する化合物の骨吸
収抑制効果；生後10〜20日齢のＩＣＲ系マウスの長管骨
を摘出し、軟組織を除去した後、５％牛胎児血清を含む
α−ＭＥＭ溶液中で骨を機械的に細切し、破骨細胞を含
む全骨髄細胞を得た。この細胞を象牙片の上に、約２×
106 の細胞を５％牛胎児血清を含むα−ＭＥＭ溶液でス
ポットした。数時間後、スフィンゴシン骨格を有する化
合物を 50ng/mlの濃度となるように添加した５％牛胎児
血清を含むα−ＭＥＭ溶液を加え、５％二酸化炭素存在
下、37℃で５日間培養し、破骨細胞の骨吸収活性を調べ
た。培養後、象牙片上の細胞を剥がしてヘマトキシリン
染色し、画像解析装置（ＰＩＡＳＬＡ−５５５、ＰＩＡ
Ｓ社製）により画像解析して、骨吸収窩(pit) 数を測定
した。そして、次式で定義される骨吸収活性（％）を求
め、骨吸収抑制効果を評価した。 骨吸収活性（％）＝（骨吸収窩数／無添加群の骨吸収窩
数）×100 なお、スフィンゴシン骨格を有する化合物としては、参
考例１〜４で得られた画分Ａ〜Ｋを使用した。その結果
を表１に示す。Test Example 1 Bone resorption inhibitory effect of compound having sphingosine skeleton; α-MEM containing 5% fetal calf serum after removing long bones of ICR mice 10-20 days old after birth and removing soft tissues The bone was mechanically minced in the solution to obtain whole bone marrow cells including osteoclasts. Place this cell on a piece of ivory, about 2x
10 6 cells were spotted with an α-MEM solution containing 5% fetal calf serum. After several hours, an α-MEM solution containing 5% fetal calf serum to which a compound having a sphingosine skeleton was added to a concentration of 50 ng / ml was added, and the mixture was cultured at 37 ° C. for 5 days in the presence of 5% carbon dioxide. The bone resorption activity of osteoclasts was examined. After the culture, the cells on the ivory piece were peeled off, stained with hematoxylin, and analyzed using an image analyzer (PIASLA-555, PIA
The image was analyzed by a company (manufactured by S company), and the number of bone resorption pits was measured. Then, the bone resorption activity (%) defined by the following formula was determined, and the bone resorption inhibiting effect was evaluated. Bone resorption activity (%) = (number of bone resorption pits / number of bone resorption pits in non-addition group) × 100 As the compound having a sphingosine skeleton, fractions A to K obtained in Reference Examples 1 to 4 were used. did. Table 1 shows the results.
【００１５】[0015]
【表１】 ──────────────────── 試験試料 骨吸収活性（％，±SD） ──────────────────── 画分Ａ 53.4 ±7.8 画分Ｂ 56.5 ±8.4 画分Ｃ 46.8 ±5.7 画分Ｄ 67.6 ±4.5 画分Ｅ 54.3 ±7.5 画分Ｆ 51.5 ±6.4 画分Ｇ 57.3 ±5.1 画分Ｈ 50.6 ±4.8 画分Ｉ 65.3 ±3.4 画分Ｊ 42.3 ±4.6 画分Ｋ 50.5 ±3.9 ────────────────────[Table 1] ──────────────────── Test sample Bone resorption activity (%, ± SD) ───────────────分 Fraction A 53.4 ± 7.8 Fraction B 56.5 ± 8.4 Fraction C 46.8 ± 5.7 Fraction D 67.6 ± 4.5 Fraction E 54.3 ± 7.5 Fraction F 51.5 ± 6.4 Fraction G 57.3 ± 5.1 Fraction H 50.6 ± 4.8 Fraction I 65.3 ± 3.4 Fraction J 42.3 ± 4.6 Fraction K 50.5 ± 3.9 ────────────────────
【００１６】スフィンゴシン骨格を有する化合物を添加
した培地で培養すると、無添加の培地で培養した時に比
べて、骨吸収が抑制されており、スフィンゴシン骨格を
有する化合物が優れた骨吸収抑制効果を示すことが確認
できた。When cultured in a medium to which a compound having a sphingosine skeleton is added, bone resorption is suppressed as compared to when cultured in a medium without addition, and the compound having a sphingosine skeleton exhibits an excellent bone resorption inhibiting effect. Was confirmed.
【００１７】[0017]
【試験例２】スフィンゴシン骨格を有する化合物の骨吸
収防止及び骨強化作用；参考例１で得られた画分Ａ及び
参考例３で得られた画分Ｊについて、骨粗鬆症モデルラ
ットを用いた投与試験により、骨吸収防止効果を調べ
た。また、画分Ａ及びＪに吸収性の良い牛乳由来のカル
シウム剤（乳Ca：特開平4-306622号公報参照）及びビタ
ミンＤ（ＶＤ） 200IUを加えて同様の試験を行った。試
験動物に投与した飼料の組成は、表２に示すように、各
成分を配合した原料に必要に応じてスフィンゴシン骨格
を有する化合物を添加した。飼料中のカルシウム量とリ
ン量は共に全ての群で飼料100g当たり 300mgになるよう
にし、カルシウム：リン比を１：１とした。そして、こ
の飼料を 0.3％添加して試験を行った。[Test Example 2] Bone resorption-preventing and bone-strengthening effects of a compound having a sphingosine skeleton; administration test of fraction A obtained in Reference Example 1 and fraction J obtained in Reference Example 3 using osteoporosis model rats The effect of preventing bone resorption was examined. A similar test was carried out by adding to fractions A and J a calcium agent derived from milk having good absorbability (milk Ca: see JP-A-4-306622) and 200 IU of vitamin D (VD). As shown in Table 2, the composition of the feed administered to the test animals was such that a compound having a sphingosine skeleton was added to the raw material in which each component was blended, if necessary. The amount of calcium and phosphorus in the feed was 300 mg per 100 g of feed in all groups, and the calcium: phosphorus ratio was 1: 1. Then, a test was conducted by adding 0.3% of this feed.
【００１８】[0018]
【表２】 ──────────────────────────────────── 画分 画分＋乳Ca2)＋ＶＤ3) 対照 シャム ─────── ─────────── Ａ Ｊ Ａ Ｊ ──────────────────────────────────── 蔗糖 50.0 50.0 50.0 50.0 50.0 50.0 カゼイン 20.0 20.0 18.0 18.0 18.0 18.0 コーンスターチ 15.0 15.0 15.0 15.0 15.0 15.0 セルロース 5.0 5.0 5.0 5.0 5.0 5.0 トウモロコシ油 5.0 5.0 5.0 5.0 5.0 5.0 ビタミン混合 1.0 1.0 1.0 1.0 1.0 1.0 （コリン含む） ミネラル混合 4.0 1) 4.0 1) 4.0 1) 4.0 1) 4.0 2) 4.0 2) ──────────────────────────────────── （単位：g/100g） 画分Ａ − − 0.0001 − 0.0001 − 画分Ｊ − − − 0.0001 − 0.0001 ──────────────────────────────────── （単位：重量％）[Table 2] ──────────────────────────────────── Fraction Fraction + milk Ca 2) + VD 3) Contrast Siam ─────────── AJA Ｊ蔗 Sucrose 50.0 50.0 50.0 50.0 50.0 50.0 Casein 20.0 20.0 18.0 18.0 18.0 18.0 Corn starch 15.0 15.0 15.0 15.0 15.0 15.0 Cellulose 5.0 5.0 5.0 5.0 5.0 5.0 Corn oil 5.0 5.0 5.0 5.0 5.0 5.0 Vitamin mixture 1.0 1.0 1.0 1.0 1.0 1.0 (including choline) Mineral mixture 4.0 1) 4.0 1) 4.0 1) 4.0 1) 4.0 2) 4.0 2) ──────────────────── ──────────────── (Unit: g / 100g) Fraction A − − 0.0001 − 0.0001 − Fraction J − − − 0.0001 − 0.0001 ───────── ──────────────────── ────── (unit:% by weight)
【００１９】1) 炭酸カルシウムをカルシウム源とし
た。 2) 牛乳由来のカルシウム剤をカルシウム源とした。 3) ビタミンＤ 200IUを配合した。 試験動物として、32週齢のＳＤ系雌性ラットを用いた。
骨粗鬆症モデルラットは、一週間予備飼育した後に卵巣
摘出手術を施し、低カルシウム食で２カ月間飼育するこ
とにより作成した。また、疑似手術を施し、卵巣を摘出
しないシャムラットも７匹作成した。投与試験は、１試
験群７匹に群分けし、表２の試験食を１カ月間投与して
行った。試験食投与後、各実験群のラットの大腿骨を摘
出し、骨塩量測定装置で骨塩量を測定し、破断特性測定
装置で骨強度を測定した。その結果を表３及び表４に示
す。1) Calcium carbonate was used as a calcium source. 2) A calcium preparation derived from milk was used as a calcium source. 3) 200 IU of vitamin D was added. As test animals, 32-week-old SD female rats were used.
Osteoporosis model rats were prepared by pre-breeding for one week, performing oophorectomy, and breeding on a low calcium diet for two months. In addition, 7 sham rats were prepared by sham operation without removing the ovaries. The administration test was carried out by dividing the animals into groups of 7 animals per test group and administering the test meals in Table 2 for one month. After the administration of the test meal, the femurs of the rats in each experimental group were excised, the amount of bone mineral was measured using a bone mineral amount measuring device, and the bone strength was measured using a breaking characteristic measuring device. The results are shown in Tables 3 and 4.
【００２０】[0020]
【表３】 [Table 3]
【００２１】表３に示したように、大腿骨の骨塩量は、
対照群に較べて、画分Ａ及びＪ群で統計的に有意に高い
値を示した。このことから、スフィンゴシン骨格を有す
る化合物には骨吸収防止効果があることが判った。ま
た、吸収性の良い乳カルシウム及びビタミンＤを加える
ことにより、その効果はさらに増大することが判った。As shown in Table 3, the amount of bone mineral in the femur was
Compared with the control group, the fractions A and J showed statistically significantly higher values. From this, it was found that the compound having a sphingosine skeleton has an effect of preventing bone resorption. It was also found that the effect was further increased by adding milk calcium and vitamin D having good absorbability.
【００２２】[0022]
【表４】 ────────────────────────── 骨破断力（106 dyn ） ────────────────────────── シャム 12.8 ± 2.9* 対照 6.4 ± 1.7 画分Ａ 8.2 ± 1.5* 画分Ｊ 8.4 ± 1.9* 画分Ａ＋乳Ca＋ＶＤ 9.1 ± 2.1* 画分Ｊ＋乳Ca＋ＶＤ 9.5 ± 2.4* ────────────────────────── * 対照群に対して有意差あり (P<0.05)[Table 4] ────────────────────────── Bone breaking force (10 6 dyn) ──────────── ────────────── Sham 12.8 ± 2.9 * Control 6.4 ± 1.7 Fraction A 8.2 ± 1.5 * Fraction J 8.4 ± 1.9 * Fraction A + milk Ca + VD 9.1 ± 2.1 * Fraction J + milk Ca + VD 9.5 ± 2.4 * ────────────────────────── * Significantly different from control group (P <0.05)
【００２３】表４に示したように、大腿骨の破断力は対
照群に較べて、画分Ａ及びＪ群で統計的に有意に高い値
を示した。このことから、スフィンゴシン骨格を有する
化合物には骨強化作用があることが判った。また、吸収
性の良い乳カルシウム及びビタミンＤを加えることによ
り、その効果はさらに増大することが判った。なお、ビ
タミンＤに代えてビタミンＫを加えても、同様の結果で
あった。As shown in Table 4, the fracture strength of the femur was statistically significantly higher in the fractions A and J than in the control group. From this, it was found that the compound having a sphingosine skeleton has a bone strengthening effect. It was also found that the effect was further increased by adding milk calcium and vitamin D having good absorbability. Similar results were obtained when vitamin K was added instead of vitamin D.
【００２４】[0024]
【試験例３】表５の配合の原料に牛乳由来のガングリオ
シド0.000008重量％及びビタミンＤ200IUを加えて混合
して容器に充填し、加熱滅菌して飲料を製造した。な
お、対照群では、表５の配合の原料にアルブミン0.0000
5 重量％及びビタミンＤ 200IUを加えた。Test Example 3 0.000008% by weight of milk-derived ganglioside and 200IU of vitamin D were added to the raw materials having the composition shown in Table 5, mixed, filled into a container, and sterilized by heating to produce a beverage. In the control group, albumin 0.0000
5% by weight and 200 IU of vitamin D were added.
【００２５】[0025]
【表５】 ─────────────────────── 結晶ブドウ糖 15.0 （重量％） カルシウム 0.5 水 74.0 ────────────────────────[Table 5] 結晶 Crystal glucose 15.0 (% by weight) Calcium 0.5 Water 74.0 ──────────── ────────────
【００２６】変形性関節症 (関節の開裂の収縮) の女性
患者20人をボランティアとして、10人ずつ２群に分け、
上記の飲料を１ヶ月間飲用してもらい、飲用開始前と飲
用終了後に、骨吸収の骨代謝マーカーである尿中デオキ
シピリジノリン量を測定して評価した。また、問診を行
って症状の変化を調べた。その結果を表６及び表７に示
す。As volunteers, 20 female patients with osteoarthritis (shrinkage of joint dehiscence) were divided into 2 groups of 10 patients.
The above-mentioned drink was drunk for one month, and before and after drinking, the amount of urinary deoxypyridinoline, a bone metabolic marker for bone resorption, was measured and evaluated. In addition, interviews were conducted to examine changes in symptoms. The results are shown in Tables 6 and 7.
【００２７】[0027]
【表６】 ────────────────────────── デオキシピリジノリン減少量 (nM/mM Cr) ────────────────────────── 対照群 0.35 ± 0.4 試験群 0.84 ± 0.3* ────────────────────────── * 対照群に対して有意差あり (P<0.05)[Table 6] 減少 Deoxypyridinoline reduction (nM / mM Cr) ──────── ────────────────── Control group 0.35 ± 0.4 Test group 0.84 ± 0.3 * ───────────────────── ───── * Significantly different from control group (P <0.05)
【００２８】表６に示すように、カルシウム及びビタミ
ンを配合した対照群においてもデオキシピリジノリン量
は減少していたが、試験群ではさらに大きく減少してい
た。この結果から、スフィンゴシン骨格を有する化合物
を配合した飲料を飲用することにより、骨の破壊による
骨吸収が極めてよく抑えられていることが判った。As shown in Table 6, the amount of deoxypyridinoline was also reduced in the control group containing calcium and vitamins, but further decreased in the test group. From this result, it was found that by drinking a beverage containing a compound having a sphingosine skeleton, bone resorption due to bone destruction was extremely well suppressed.
【００２９】[0029]
【表７】 ────────────────────────────── 対照群 試験群 ────────────────── 開始前 終了後 開始前 終了後 ────────────────────────────── 物理的圧迫の関節痛 10 9 10 10 動作時の関節痛 5 5 5 1 就寝時の関節痛 6 6 7 4 疲労時の関節痛 9 8 8 4 脱力感 6 6 7 2 開裂全体の関節痛 9 8 9 4 ────────────────────────────── （単位：人／１０人）[Table 7] ────────────────────────────── Control group Test group ────────────前 Before starting After finishing Before starting After finishing 関節 Joint pain due to physical compression 10 9 10 10 Joint pain during operation 5 5 5 1 Joint pain at bedtime 6 6 7 4 Joint pain during fatigue 9 8 8 4 Weakness 6 6 7 2 Joint pain throughout laceration 9 8 9 4 ──── ────────────────────────── (Unit: 10 people)
【００３０】表７に示すように、関節痛に関しても、ス
フィンゴシン骨格を有する化合物を配合した飲料を飲用
することにより、痛みが軽減していることが判った。な
お、スフィンゴシン骨格を有する化合物を配合したチー
ズでも同様の傾向が見られた。[0030] As shown in Table 7, it was found that the pain was reduced by drinking a beverage containing a compound having a sphingosine skeleton with respect to joint pain. A similar tendency was observed in cheese containing a compound having a sphingosine skeleton.
【００３１】[0031]
【実施例１】飲料の製造；表８の配合の原料に牛乳由来
のガングリオシド0.00005 重量％及びビタミンＤ200IU
を加えて混合して容器に充填し、加熱滅菌して、骨関節
疾患の予防及び改善効果を賦与した飲料を製造した。Example 1 Production of a beverage ; 0.00005% by weight of gangliosides derived from milk and 200 IU of vitamin D
Was added, mixed, filled into a container, and sterilized by heating to produce a beverage having an effect of preventing and improving osteoarthritis.
【００３２】[0032]
【表８】 ───────────────────────── 混合異性化糖 15.0（重量％） 果汁 10.0 クエン酸 0.5 香料 0.1 カルシウム 0.5 水 73.9 ─────────────────────────[Table 8] ───────────────────────── Mixed isomerized sugar 15.0 (wt%) Fruit juice 10.0 Citric acid 0.5 Flavor 0.1 Calcium 0.5 Water 73.9 ─ ────────────────────────
【００３３】[0033]
【実施例２】錠剤の製造；表９の配合の原料に牛乳由来
のガングリオシド0.0001重量％及びビタミンＤ 200IUを
加えて混合し、加圧成型して、骨関節疾患の予防及び改
善効果を賦与した錠剤を製造した。Example 2 Production of tablets : 0.0001% by weight of ganglioside derived from milk and 200IU of vitamin D were added to the raw materials having the composition shown in Table 9 and mixed, followed by press molding to impart the effect of preventing and improving osteoarthritis. Tablets were manufactured.
【００３４】[0034]
【表９】 ────────────────────────── 含水結晶ブドウ糖 93.5（重量％） カルシウム 5.0 シュガーエステル 1.0 香料 0.5 ────────────────────────── [Table 9] 結晶 Hydrous glucose 93.5 (% by weight) Calcium 5.0 Sugar ester 1.0 Fragrance 0.5 ───── ─────────────────────
【００３５】[0035]
【実施例３】ビスケットの製造；表１０の配合の原料に
牛脳由来のガングリオシド0.00001 重量％を加えて混合
してドウを作成し、成型した後、ばい焼して、骨関節疾
患の予防及び改善効果を賦与したビスケットを製造し
た。Example 3 Production of biscuits ; 0.00001% by weight of bovine brain-derived ganglioside was added to the raw materials having the composition shown in Table 10 and mixed to prepare a dough, which was then molded and then roasted to prevent osteoarticular diseases. A biscuit with an improved effect was manufactured.
【００３６】[0036]
【表１０】 ──────────────────────── 小麦粉 50.0（重量％） 砂糖 20.0 食塩 0.5 マーガリン 12.5 卵 12.5 水 3.7 炭酸水素ナトリウム 0.1 重炭酸アンモニウム 0.2 炭酸カルシウム 0.5 ────────────────────────[Table 10] ──────────────────────── Flour 50.0 (% by weight) Sugar 20.0 Salt 0.5 Margarine 12.5 Egg 12.5 Water 3.7 Sodium bicarbonate 0.1 Bicarbonate Ammonium 0.2 Calcium carbonate 0.5 ────────────────────────
【００３７】[0037]
【実施例４】ゼリーの製造；表１１の配合の原料に牛乳
由来のスフィンゴミエリン0.00001 重量％を加えて混合
し、容器に充填した後、加熱滅菌して、骨関節疾患の予
防及び改善効果を賦与したゼリーを製造した。Example 4 Production of jelly ; 0.00001% by weight of sphingomyelin derived from milk was added to the raw materials having the composition shown in Table 11, mixed, filled into a container, and then sterilized by heating to prevent and improve osteoarthritis. The applied jelly was produced.
【００３８】[0038]
【表１１】 ────────────────────────── 果糖 20.0（重量％） グラニュー糖 15.0 水飴 5.0 寒天 1.0 香料 0.1 カルシウム 0.1 水 58.8 ────────────────────────── [Table 11] ────────────────────────── Fructose 20.0 (% by weight) Granulated sugar 15.0 Ginger syrup 5.0 Agar 1.0 Flavor 0.1 Calcium 0.1 Water 58.8 ─ ─────────────────────────
【００３９】[0039]
【実施例５】プロセスチーズの製造；表１２の配合の原
料に牛乳由来のガングリオシド0.0001重量％を加えて混
合し、乳化温度85℃で乳化して、骨関節疾患の予防及び
改善効果を賦与したプロセスチーズを製造した。Example 5 Production of Processed Cheese ; 0.0001% by weight of milk-derived ganglioside was added to the raw materials having the composition shown in Table 12, and the mixture was emulsified at an emulsification temperature of 85 ° C. to provide the effect of preventing and improving osteoarthritis. Processed cheese was manufactured.
【００４０】[0040]
【表１２】 ──────────────────────── ゴーダチーズ 43.0（重量％） チェダーチーズ 43.5 クエン酸ナトリウム 2.0 牛乳由来のカルシウム 1.0 水 10.5 ────────────────────────[Table 12] ゴ ー Gouda cheese 43.0 (% by weight) Cheddar cheese 43.5 Sodium citrate 2.0 Calcium from milk 1.0 Water 10.5 ─ ───────────────────────
【００４１】[0041]
【実施例６】12％脱脂乳に90℃で20分間加熱殺菌した
後、ラクトバチルス・デルブルッキー・サブスピーシー
ズ・ブルガリクス(L.delbrueckii subsp.bulgaricus)及
びストレプトコッカス・サーモフィルス(S.thermophilu
s)をそれぞれ接種し、二種類のスターターカルチャーを
得た。そして、牛乳を主体とするヨーグルトミックスを
主成分として、表１３の配合の原料に牛脳由来のガング
リオシド0.00001 重量％を加えて混合した後、常法に従
って発酵冷却を行い、骨関節疾患の予防及び改善効果を
賦与したヨーグルトを製造した。Example 6 After heat sterilization in 12% skim milk at 90 ° C. for 20 minutes, L. delbrueckii subsp. Bulgaricus (L. delbrueckii subsp. Bulgaricus) and Streptococcus thermophilus (S. thermophilu)
s) were inoculated respectively to obtain two types of starter cultures. Then, after mixing yogurt mix mainly composed of milk as a main component and adding 0.00001% by weight of ganglioside derived from bovine brain to the raw materials having the composition shown in Table 13, fermentation cooling was performed according to a conventional method to prevent osteoarthritis and prevent osteoarthritis. Yogurt with improved effect was produced.
【００４２】[0042]
【表１３】 ──────────────────────── ヨーグルトミックス 97.0（重量％） 培養物(L.bulgaricus) 1.5 培養物(S.thermophilus) 1.5 ────────────────────────Table 13 ──────────────────────── Yogurt mix 97.0 (% by weight) Culture (L. bulgaricus) 1.5 Culture (S. thermophilus) 1.5 ────────────────────────
【００４３】[0043]
【実施例７】ドッグフードの製造；表１４の配合の原料
に牛乳由来のガングリオシド0.0002重量％を加えて混合
し、骨関節疾患の予防及び改善効果を賦与したドッグフ
ード（イヌ飼育用飼料）を製造した。Example 7 Manufacture of dog food ; 0.0002% by weight of ganglioside derived from milk was added to the raw materials having the composition shown in Table 14 and mixed to prepare a dog food (feed for canine breeding) having the effects of preventing and improving osteoarthritis. .
【００４４】[0044]
【表１４】 ─────────────────────── 大豆粕 12.0（重量％） 脱脂粉乳 14.0 大豆油 4.0 コーン油 2.0 パーム油 28.0 トウモロコシ澱粉 15.0 小麦粉 9.0 ふすま 2.0 ビタミン混合物 9.0 ミネラル混合物 2.0 セルロース 3.0 ───────────────────────[Table 14] ─────────────────────── Soybean meal 12.0 (wt%) skim milk powder 14.0 soybean oil 4.0 corn oil 2.0 palm oil 28.0 corn starch 15.0 flour 9.0 Bran 2.0 Vitamin mixture 9.0 Mineral mixture 2.0 Cellulose 3.0 ───────────────────────
【００４５】[0045]
【発明の効果】セラミド、スフィンゴミエリン、スフィ
ンゴ糖脂質、ガングリオシドなどのスフィンゴシン骨格
を有する化合物を有効成分とすることにより、骨粗鬆
症、骨折、腰痛、リウマチなどの骨関節疾患の予防及び
改善剤を提供することができる。また、セラミド、スフ
ィンゴミエリン、スフィンゴ糖脂質、ガングリオシドな
どのスフィンゴシン骨格を有する化合物を配合すること
により、骨粗鬆症、骨折、腰痛、リウマチなどの骨関節
疾患の予防及び改善効果を賦与した飲食品又は飼料を提
供することができる。さらに、上記した骨関節疾患の予
防及び改善剤に、カルシウム剤、ビタミンＤ、ビタミン
Ｋを加えることにより、あるいは上記した骨関節疾患の
予防及び改善効果を賦与した飲食品又は飼料に、カルシ
ウム剤、ビタミンＤ、ビタミンＫを加えることにより、
それぞれの効果を高めることができる。EFFECT OF THE INVENTION By using a compound having a sphingosine skeleton such as ceramide, sphingomyelin, glycosphingolipid, and ganglioside as an active ingredient, an agent for preventing and improving osteoarthritis such as osteoporosis, bone fracture, low back pain and rheumatism is provided. be able to. Further, by blending a compound having a sphingosine skeleton such as ceramide, sphingomyelin, glycosphingolipid, and ganglioside, osteoporosis, bone fracture, low back pain, food and drink or feed that has been given the effect of preventing and improving osteoarticular diseases such as rheumatism. Can be provided. Further, a calcium agent, vitamin D, vitamin K added to the above-mentioned osteoarthritis prevention and amelioration agent, or a food or drink or feed that has the osteoarthritis prevention and amelioration effect described above, By adding vitamin D and vitamin K,
Each effect can be enhanced.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ａ６１Ｐ 19/10 Ａ６１Ｐ 19/10 (72)発明者 川上 浩 埼玉県川越市藤間204−５ (72)発明者 青江 誠一郎 埼玉県狭山市新狭山２−８−９ワコー第二 新狭山マンション406 Ｆターム(参考） 4B018 LB01 LB02 LB06 LB07 LB08 MD04 MD09 MD18 MD23 MD27 MD28 MD30 MD52 ME05 MF02 4C086 AA01 AA02 DA14 DA42 EA05 EA06 HA04 MA01 MA02 MA04 MA08 MA52 NA05 NA14 ZA96 ZA97 ZB15 ZC20 ZC61 ZC75 4C206 AA01 AA02 CB28 FA03 GA23 GA25 MA01 MA02 MA04 MA22 MA28 MA30 MA72 NA05 NA14 ZA96 ZA97 ZB15 ZC20 ZC61 ZC75 ──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme coat ゛ (Reference) A61P 19/10 A61P 19/10 (72) Inventor Hiroshi Kawakami 204-5 Fujima, Kawagoe-shi, Saitama (72) Invention Person Seiichiro Aoe 2-8-9 Shinsayama, Sayama City, Saitama Prefecture Wako 2 Shinsayama Mansion 406 F-term (reference) 4B018 LB01 LB02 LB06 LB07 LB08 MD04 MD09 MD18 MD23 MD27 MD28 MD30 MD52 ME05 MF02 4C086 AA01 AA02 DA14 DA42 EA05 EA04 HA04 MA01 MA02 MA04 MA08 MA52 NA05 NA14 ZA96 ZA97 ZB15 ZC20 ZC61 ZC75 4C206 AA01 AA02 CB28 FA03 GA23 GA25 MA01 MA02 MA04 MA22 MA28 MA30 MA72 NA05 NA14 ZA96 ZA97 ZB15 ZC20 ZC61 ZC75
Claims (5)
効成分とする骨関節疾患の予防及び改善剤。1. A preventive and ameliorating agent for osteoarticular diseases comprising a compound having a sphingosine skeleton as an active ingredient.
セラミド、スフィンゴミエリン、スフィンゴ糖脂質又は
ガングリオシドである請求項１記載の骨関節疾患の予防
及び改善剤。2. The compound having a sphingosine skeleton,
The agent according to claim 1, which is ceramide, sphingomyelin, glycosphingolipid or ganglioside.
ビタミンＫから選ばれる一種以上の物質を含有する請求
項１又は２記載の骨関節疾患の予防及び改善剤。3. The preventive and ameliorating agent for osteoarticular diseases according to claim 1, further comprising one or more substances selected from calcium preparations, vitamin D and vitamin K.
合して骨関節疾患の予防及び改善効果を賦与した飲食品
又は飼料。4. A food or drink or feed which has a compound having a sphingosine skeleton and has an effect of preventing and improving osteoarthritis.
ビタミンＫから選ばれる一種以上の物質を配合した請求
項４記載の飲食品又は飼料。5. The food or drink or feed according to claim 4, further comprising one or more substances selected from calcium agents, vitamin D and vitamin K.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34021199A JP2001158736A (en) | 1999-11-30 | 1999-11-30 | Agent for preventing and improving osteoarthropathy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34021199A JP2001158736A (en) | 1999-11-30 | 1999-11-30 | Agent for preventing and improving osteoarthropathy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2001158736A true JP2001158736A (en) | 2001-06-12 |
Family
ID=18334770
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP34021199A Pending JP2001158736A (en) | 1999-11-30 | 1999-11-30 | Agent for preventing and improving osteoarthropathy |
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| Country | Link |
|---|---|
| JP (1) | JP2001158736A (en) |
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