JP2001158735A - Agent for preventing and improving periodontal disease - Google Patents
Agent for preventing and improving periodontal diseaseInfo
- Publication number
- JP2001158735A JP2001158735A JP34017499A JP34017499A JP2001158735A JP 2001158735 A JP2001158735 A JP 2001158735A JP 34017499 A JP34017499 A JP 34017499A JP 34017499 A JP34017499 A JP 34017499A JP 2001158735 A JP2001158735 A JP 2001158735A
- Authority
- JP
- Japan
- Prior art keywords
- fraction
- periodontal disease
- ganglioside
- preventing
- vitamin
- 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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- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol 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
- 239000006228 supernatant 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
- 239000012085 test solution Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 235000010493 xanthan gum Nutrition 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歯周病の予防及び改
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歯周病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 periodontal disease comprising a compound having a sphingosine skeleton as an active ingredient. The present invention also 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 periodontal disease.
【０００２】[0002]
【従来の技術】近年、歯周病が大きな社会問題となって
いる。歯周病は、虫歯と異なり、歯の根元を弱らせて虫
歯のない歯をも使えなくする病気である。多くの人は、
歯周病の兆候を示しており、むしろ虫歯よりも怖い病気
であるといえる。現在、歯周病の予防法としては、歯垢
を除去することや抗菌剤含有のうがい剤（マウスウォッ
シュ）などを使用したうがいなど、原因菌となる微生物
の繁殖を防止するという観点からの予防が行われている
が、これらの方法は過度に進行した症状に対しては効果
が小さいと考えられている。すなわち、歯周病の末期に
は、歯槽骨の減少が見られ、一度歯槽骨が失われると再
生され難くなる。そして、歯周病により歯を失うと、食
物が食べ難くなる外に、痛みを伴うことなどから生活に
支障をきたすので、有効な歯周病の予防及び治療手段が
求められている。このように、現状では、歯槽骨の減少
を抑制する効果を有する歯周病の予防及び改善剤は知ら
れていない。2. Description of the Related Art In recent years, periodontal disease has become a major social problem. Periodontal disease, unlike tooth decay, is a disease that weakens the roots of teeth and makes teeth without tooth decay unusable. Many people
It shows signs of periodontal disease and can be said to be a scarier disease than caries. At present, periodontal disease prevention methods include the removal of plaque and the use of a gargle containing an antibacterial agent (mouthwash) to prevent the growth of microorganisms that cause causative bacteria. However, these methods are thought to be less effective for over-advanced symptoms. That is, at the end of periodontal disease, alveolar bone decreases, and once the alveolar bone is lost, it becomes difficult to regenerate. In addition, if teeth are lost due to periodontal disease, food becomes difficult to eat and, at the same time, life is hindered due to pain and the like. Therefore, effective means for preventing and treating periodontal disease is required. As described above, at present, no preventive or ameliorating agent for periodontal disease having an effect of suppressing alveolar bone loss is known.
【０００３】[0003]
【発明が解決しようとする課題】上記するように、歯周
病は、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、
歯周病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歯
周病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歯周病の予防及
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
上記の歯周病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
合物を配合して歯周病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, periodontal disease has become a major social problem, and there is a need for a method for preventing and improving these symptoms. We have:
Intensive research has been conducted to obtain a substance having a prophylactic and ameliorating effect on periodontal disease.As a result, compounds having a sphingosine skeleton such as ceramide, sphingomyelin, glycosphingolipids, and gangliosides contained in milk and bovine brain have been studied. It has been found that it has an effect of preventing and improving the disease. 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 prophylactic and ameliorating agent for periodontal disease comprising a compound having a sphingosine skeleton as an active ingredient, and a calcium agent, vitamin D and vitamin K, wherein one or more substances selected from vitamin D and vitamin K are added. An object of the present invention is to provide an agent for preventing and improving periodontal disease. Further, the present invention provides a food or drink or feed provided with a preventive and ameliorating effect on periodontal disease by compounding a compound having a sphingosine skeleton, and one or more kinds selected from calcium, 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.
【０００４】[0004]
【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歯周病の
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歯周病の予防及び改
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 periodontal disease. In the present invention, compounds having a sphingosine skeleton such as ceramide, sphingomyelin, glycosphingolipids, and gangliosides are added to foods and drinks and feeds to provide the effect of preventing and improving periodontal disease. 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.
【０００５】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。[0005] 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.
【０００６】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歯周病
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歯周病の予防及び改
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, glycosphingolipid, and ganglioside, may be those derived from chemical products, 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 a preventive and ameliorating agent for periodontal disease comprising a compound having a sphingosine skeleton as an active ingredient, one or more substances selected from calcium, vitamin D and vitamin K are added. . Further, in the present invention, in order to enhance the effect of food and drink and feed that imparts the effect of preventing and improving periodontal disease by compounding the compound having a sphingosine skeleton described above,
One or more substances selected from calcium, vitamin D and vitamin K are added. 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.
【０００７】[0007]
【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、歯周病の予防
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、歯周病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
して歯周病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、歯周病
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 periodontal disease. An improving agent is prepared, and further, one or more substances selected from calcium, vitamin D and vitamin K are added to prepare an agent for preventing and improving periodontal disease. Further, in the present invention, a ceramide having a sphingosine skeleton derived from a chemical product, or milk or bovine brain, sphingomyelin,
Glycosphingolipids, compounds such as gangliosides are blended to prepare foods and drinks or feeds that have the effect of preventing and improving periodontal disease, and further, one or more substances selected from calcium, vitamin D and vitamin K are added. Thus, a food or drink or feed having the effect of preventing and improving periodontal disease is prepared.
【０００８】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、歯周病を予防及び改善す
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、歯周病の予防及び改善
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。In the present invention, periodontal disease can be prevented and ameliorated by taking a compound having a sphingosine skeleton at a dose of 1 μg to 10 mg per adult per day in several divided doses. 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 preparations, vitamin D and vitamin K, the effects of preventing and improving periodontal disease can be enhanced. In addition, as food and drink, for example, milk, milk drink, juice, jelly, biscuit,
Bread, noodles, sausages and the like can be mentioned. Next, the present invention will be described in detail with reference to Examples and Test Examples.
【０００９】[0009]
【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.
【００１０】[0010]
【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.
【００１１】[0011]
【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.
【００１２】[0012]
【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.
【００１３】[0013]
【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日〜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−ＭＥＮ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−ＭＥＮ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−ＭＥＮ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、ＰＩ
ＡＳ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 a compound having a sphingosine skeleton; a long bone of an ICR mouse 10 to 20 days old was removed, soft tissues were removed, and α-containing 5% fetal bovine serum was used. Bone was mechanically minced in MEN solution to obtain whole bone marrow cells including osteoclasts. Place these cells on ivory pieces for approximately 2
× 10 6 cells were spotted with α-MEN solution containing 5% fetal calf serum. A few hours later, an α-MEN solution containing 5% fetal bovine 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 pieces were peeled off and stained with hematoxylin, and then analyzed using an image analyzer (PIASLA-555, PI
AS) (manufactured by AS Corporation), 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.
【００１４】[0014]
【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) ──────── ─────────────────── 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 Min 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 ─────────────── ────────────
【００１５】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.
【００１６】[0016]
【試験例２】歯槽骨減少量の評価 ６週齢のゴールデンハムスターを１週間予備飼育した
後、エーテル麻酔下で、M1の歯頸部に滅菌した手術用縫
合絹糸 No4を５重に巻き付けて、Keyes らの飼料(D#200
0：Keyes,P.H. and Jordan, Archs. Oral. Biol., vol.
9, pp.377-400,1964) で飼育することにより歯周病を発
病させた。次いで、このゴールデンハムスター６匹ずつ
を、対照群、画分Ａ群、画分Ｅ群及び画分Ｊ群の４群に
分け、画分Ａ群、画分Ｅ群及び画分Ｊ群は、一日２回、
各画分 4μg を適当に希釈した試験液で口腔内を約10分
間絶えず浸す処置を行った。処置開始から４週間後、
2.5％グルタルアルデヒド溶液(pH 7.4)を用いて約20分
間固定灌流した後、下顎骨両側を摘出した。歯槽骨減少
量の評価は、 2.5％グルタルアルデヒド溶液で固定した
後、軟Ｘ線撮影して、写真を画像解析装置（ＰＩＡＳＬ
Ａ−５５５、ＰＩＡＳ社製）を用い、M1付近のエナメル
セメント境と歯槽骨頂間の面積を計測し、歯槽骨減少量
として評価した。その結果を表２に示す。[Test Example 2] Evaluation of alveolar bone loss A 6-week-old golden hamster was preliminarily reared for 1 week, and then under sterile ether anesthesia, a sterilized surgical suture silk thread No4 was wound around the cervical region of M1 five times. Keyes et al. Feed (D # 200
0: Keyes, PH and Jordan, Archs. Oral. Biol., Vol.
9, pp. 377-400, 1964) caused periodontal disease. Next, each of the six golden hamsters was divided into four groups: a control group, a fraction A group, a fraction E group, and a fraction J group. The fraction A group, the fraction E group, and the fraction J group were one group. Twice a day,
A treatment was carried out in which 4 μg of each fraction was constantly immersed in the oral cavity for about 10 minutes with an appropriately diluted test solution. Four weeks after the treatment started,
After fixed perfusion with a 2.5% glutaraldehyde solution (pH 7.4) for about 20 minutes, both sides of the mandible were removed. To evaluate the alveolar bone loss, after fixing with a 2.5% glutaraldehyde solution, soft X-rays were taken and the photographs were taken with an image analyzer (PIASL).
A-555, manufactured by PIAS), the area between the enamel cement boundary near M1 and the alveolar bone crest was measured and evaluated as the amount of alveolar bone loss. Table 2 shows the results.
【００１７】[0017]
【表２】 ──────────────────────────────────── 画分 対照 ───────────────── Ａ Ｅ Ｊ ──────────────────────────────────── 減少面積 (mm2) ４日 0.31 0.16 * 0.18 * 0.15 * ７日 0.98 0.53 * 0.58 * 0.47 * ────────────────────────────────────＊ 対照群に対して有意差あり (P<0.05)[Table 2] 画 Fraction control ─────── Ａ AEJ ──────────────────────────────────── Decrease Area (mm 2 ) 4 days 0.31 0.16 * 0.18 * 0.15 * 7 days 0.98 0.53 * 0.58 * 0.47 * ─────────────────────────── ───────── * Significantly different from control group (P <0.05)
【００１８】表２に示すように、画分Ａ群、画分Ｅ群及
び画分Ｊ群のゴールデンハムスターは、対照群に比べ
て、明らかに歯槽骨減少量が有意に低いことが判った。
このことから、スフィンゴシン骨格を有する化合物は、
歯槽骨減少を抑制し、歯周病の予防に効果があることが
判った。なお、この効果は濃度依存的であることも判っ
た。As shown in Table 2, it was found that the alveolar bone loss was significantly lower in the golden hamsters of the fraction A group, the fraction E group and the fraction J group than the control group.
From this, the compound having a sphingosine skeleton is
It was found that it was effective in suppressing alveolar bone loss and preventing periodontal disease. This effect was also found to be concentration-dependent.
【００１９】[0019]
【実施例１】飲料の製造；表３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、歯周病
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 milk-derived ganglioside 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 periodontal disease.
【００２０】[0020]
【表３】 ───────────────────────── 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 3] ───────────────────────── Mixed isomerized sugar 15.0 (% by weight) Fruit juice 10.0 Citric acid 0.5 Flavor 0.1 Calcium 0.5 Water 73.9 ─ ────────────────────────
【００２１】[0021]
【実施例２】錠剤の製造；表４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、歯周病の予防及び改善効
果を賦与した錠剤を製造した。Example 2 Production of tablets : 0.0001% by weight of milk-derived ganglioside and 200IU of vitamin D were added to the raw materials having the composition shown in Table 4 and mixed, followed by press molding to impart the effect of preventing and improving periodontal disease. Tablets were manufactured.
【００２２】[0022]
【表４】 ────────────────────────── 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 4] 結晶 Hydrous crystalline glucose 93.5 (% by weight) Calcium 5.0 Sugar ester 1.0 Fragrance 0.5 ───── ─────────────────────
【００２３】[0023]
【実施例３】ビスケットの製造；表５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、歯周病の予
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 5 and mixed to form a dough, which was then molded and roasted to prevent periodontal disease and A biscuit with an improved effect was manufactured.
【００２４】[0024]
【表５】 ──────────────────────── 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 5] ──────────────────────── 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 ────────────────────────
【００２５】[0025]
【実施例４】ゼリーの製造；表６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、歯周病の予防及
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 6, mixed, filled into a container, and then sterilized by heating to prevent and improve the effects of periodontal disease. The applied jelly was produced.
【００２６】[0026]
【表６】 ────────────────────────── 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 6] ────────────────────────── Fructose 20.0 (% by weight) Granulated sugar 15.0 Candy sugar 5.0 Agar 1.0 Flavor 0.1 Calcium 0.1 Water 58.8 ─ ─────────────────────────
【００２７】[0027]
【実施例５】プロセスチーズの製造；表７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、歯周病の予防及び改善効
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 7 and mixed, followed by emulsification at an emulsification temperature of 85 ° C., thereby giving the effect of preventing and improving periodontal disease. Processed cheese was manufactured.
【００２８】[0028]
【表７】 ──────────────────────── 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 7] ゴ ー Gouda cheese 43.0 (% by weight) Cheddar cheese 43.5 Sodium citrate 2.0 Calcium from milk 1.0 Water 10.5 ─ ───────────────────────
【００２９】[0029]
【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８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、歯周病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 8, fermentation and cooling were performed according to a conventional method to prevent periodontal disease. Yogurt with improved effect was produced.
【００３０】[0030]
【表８】 ──────────────────────── 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 ────────────────────────８ Yogurt mix 97.0 (% by weight) Culture (L. bulgaricus) 1.5 Culture (S. thermophilus) 1.5 ────────────────────────
【００３１】[0031]
【実施例７】ドッグフードの製造；表９の配合の原料に
牛乳由来のガングリオシド0.0002重量％を加えて混合
し、歯周病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 9 and mixed to prepare a dog food (feed for canine breeding) having the effect of preventing and improving periodontal disease. .
【００３２】[0032]
【表９】 ─────────────────────── 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 9] ─────────────────────── 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 ───────────────────────
【００３３】[0033]
【実施例８】歯磨き剤の製造；表１０に示す配合の原料
に牛乳由来のスフィンゴミエリン0.0002重量％を加えて
混合したクリームを容器に充填し、歯周病の予防及び改
善用歯磨き剤を製造した。Example 8 Production of a dentifrice ; a cream prepared by adding 0.0002% by weight of sphingomyelin derived from milk to the ingredients shown in Table 10 and filling the mixture into a container to produce a dentifrice for prevention and improvement of periodontal disease. did.
【００３４】[0034]
【表１０】 ────────────────────────── グリセリン 70.0 (重量％) 二酸化ケイ素 20.0 キサンタンガム 1.0 ミントフレーバー 1.0 二酸化チタン 0.7 フッ化ナトリウム 0.3 蒸留水 7.0 ────────────────────────── [Table 10] グ リ Glycerin 70.0 (% by weight) Silicon dioxide 20.0 Xanthan gum 1.0 Mint flavor 1.0 Titanium dioxide 0.7 Sodium fluoride 0.3 Distilled water 7.0 ──────────────────────────
【００３５】[0035]
【実施例９】うがい剤の製造；表１１に示す配合の原料
に牛乳由来のスフィンゴミエリン0.0001重量％を加えて
歯周病の予防及び改善用うがい剤を製造した。Example 9 Production of a gargle : A gargle for prevention and improvement of periodontal disease was produced by adding 0.0001% by weight of sphingomyelin derived from milk to raw materials having the composition shown in Table 11.
【００３６】[0036]
【表１１】 ────────────────────────── エタノール 8.0 (重量％) 香料 1.0 ソルビトール 5.0 プロピレングリコール 5.0 蒸留水 81.0 ────────────────────────── [Table 11] ────────────────────────── Ethanol 8.0 (% by weight) Fragrance 1.0 Sorbitol 5.0 Propylene glycol 5.0 Distilled water 81.0 ──── ──────────────────────
【００３７】[0037]
【実施例１０】ガムの製造；ガムベースを水に溶解し、
表１２に示す配合の原料に牛乳由来のガングリオシド0.
0002重量％を加えて混合撹拌後、成形して、歯周病の予
防及び改善用ガムを製造した。Example 10 Production of gum; dissolving gum base in water,
Milk-derived ganglioside 0.
0002% by weight was added, mixed and stirred, and then molded to produce a gum for preventing and improving periodontal disease.
【００３８】[0038]
【表１２】 ──────────────────────── ガムベース 20.0 (重量％) コーンシロップ 10.0 デキストロース・１水和物 10.0 ラクトース 5.0 グリセリン 5.0 水 50.0 ────────────────────────[Table 12] ──────────────────────── Gum base 20.0 (% by weight) Corn syrup 10.0 Dextrose monohydrate 10.0 Lactose 5.0 Glycerin 5.0 Water 50.0 ────────────────────────
【００３９】[0039]
【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、歯周病の
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、歯周病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
した歯周病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
た歯周病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, ganglioside as an active ingredient, an agent for preventing and improving periodontal disease can be provided. In addition, by blending a compound having a sphingosine skeleton such as ceramide, sphingomyelin, glycosphingolipid, ganglioside, etc., a food or drink or feed having the effect of preventing and improving periodontal disease can be provided. Furthermore, a calcium agent, vitamin D, vitamin K is added to the above-mentioned periodontal disease preventive and ameliorating agent, or a food or drink or feed that has the above-mentioned periodontal disease preventive and ameliorating effect is provided with a calcium agent, By adding vitamin D and vitamin K, the respective effects 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 1/02 Ａ６１Ｐ 1/02 19/00 19/00 (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 LB08 MD04 MD09 MD23 MD52 ME09 MF02 4C083 AA112 AB172 AB242 AB312 AB322 AB472 AC102 AC122 AC132 AC302 AC641 AD192 AD212 AD222 AD352 AD391 AD571 AD572 CC41 DD15 DD21 DD22 DD23 DD27 DD41 EE33 4C086 AA01 AA02 DA42 EA05 EA06 MA01 MA04 MA52 NA14 ZA67 ZC71 4C206 AA01 AA02 FA03 GA23 GA25 MA01 MA04 MA72 NA14 ZA67 ZC61 ──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme coat ゛ (Reference) A61P 1/02 A61P 1/02 19/00 19/00 (72) Inventor Hiroshi Kawakami 204, Fujima, Kawagoe-shi, Saitama -5 (72) Inventor Seiichiro Aoe 2-8-9 Shin-Sayama, Sayama-shi, Saitama Prefecture Wako 2 Shin-Sayama Mansion 406 F-term (Reference) 4B018 LB08 MD04 MD09 MD23 MD52 ME09 MF02 4C083 AA112 AB172 AB242 AC102 AC122 AC132 AC132 AC302 AC641 AD192 AD212 AD222 AD352 AD391 AD571 AD572 CC41 DD15 DD21 DD22 DD23 DD27 DD41 EE33 4C086 AA01 AA02 DA42 EA05 EA06 MA01 MA04 MA52 NA14 ZA67 ZC71 4C206 AA01 AA02 FA03 GA23 GA25 MA01 MA04 MA72 NA14 ZA67 ZC61
Claims (3)
効成分とする歯周病の予防及び改善剤。An agent for preventing and improving periodontal disease, 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記載の歯周病の予防及び
改善剤。2. The compound having a sphingosine skeleton,
The preventive and ameliorating agent for periodontal disease according to claim 1, which is ceramide, sphingomyelin, glycosphingolipid or ganglioside.
合して歯周病の予防及び改善効果を賦与した飲食品又は
飼料。3. A food or drink or feed which is compounded with a compound having a sphingosine skeleton and has an effect of preventing and improving periodontal disease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34017499A JP2001158735A (en) | 1999-11-30 | 1999-11-30 | Agent for preventing and improving periodontal disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34017499A JP2001158735A (en) | 1999-11-30 | 1999-11-30 | Agent for preventing and improving periodontal disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2001158735A true JP2001158735A (en) | 2001-06-12 |
Family
ID=18334446
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP34017499A Pending JP2001158735A (en) | 1999-11-30 | 1999-11-30 | Agent for preventing and improving periodontal disease |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2001158735A (en) |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004064820A2 (en) * | 2003-01-20 | 2004-08-05 | Nederlandse Organisatie Voor Toegepast- Natuurwetenschappelijk Onderzoek Tno | Use of sphingolipids for reducing plasma cholesterol and triacylglycerol levels |
| WO2005094839A1 (en) * | 2004-03-30 | 2005-10-13 | Snow Brand Milk Products Co., Ltd. | Skin conditioning agent |
| WO2005107769A1 (en) * | 2004-05-07 | 2005-11-17 | Snow Brand Milk Products Co., Ltd. | Oral flora-improving agent, antibacterial agent and growth promoter |
| WO2007034927A1 (en) * | 2005-09-22 | 2007-03-29 | Snow Brand Milk Products Co., Ltd. | Medicine, food and drink or feed containing sphingomyelin |
| JP2007112793A (en) * | 2005-09-22 | 2007-05-10 | Snow Brand Milk Prod Co Ltd | Sphingomyelin-containing medicine, food and drink or fodder |
| JP2007246404A (en) * | 2006-03-14 | 2007-09-27 | Snow Brand Milk Prod Co Ltd | Learning ability-improving agent |
| WO2010020165A1 (en) | 2008-08-18 | 2010-02-25 | 复旦大学附属中山医院 | Promotors of ceramide’s generation |
| US7906488B2 (en) | 2004-11-30 | 2011-03-15 | Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno | Sphingolipids in treatment and prevention of steatosis and of steatosis or of hepatotoxicity and its sequelae |
| WO2011043212A1 (en) | 2009-10-05 | 2011-04-14 | 花王株式会社 | Ceramide production enhancer and moisturizing agent |
| JP2012167104A (en) * | 2005-09-22 | 2012-09-06 | Snow Brand Milk Products Co Ltd | Sphingomyelin-containing medicine |
| US8440645B2 (en) | 2008-07-31 | 2013-05-14 | Kao Corporation | Ceramide production promoter |
| WO2013162366A1 (en) * | 2012-04-27 | 2013-10-31 | Stichting Vu-Vumc | Protection of materials by sphingosine based compounds |
| WO2014034802A1 (en) | 2012-08-29 | 2014-03-06 | 花王株式会社 | Transglutaminase activator |
| US8703172B2 (en) | 2003-01-20 | 2014-04-22 | Nederlandse Organizatie voor Toegepastnatuurwetenschappelijk Onderzoek TNO | Sphingolipids for improvement of the composition of the intestinal flora |
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|---|---|---|---|---|
| WO2004064820A2 (en) * | 2003-01-20 | 2004-08-05 | Nederlandse Organisatie Voor Toegepast- Natuurwetenschappelijk Onderzoek Tno | Use of sphingolipids for reducing plasma cholesterol and triacylglycerol levels |
| WO2004064820A3 (en) * | 2003-01-20 | 2004-09-30 | Tno | Use of sphingolipids for reducing plasma cholesterol and triacylglycerol levels |
| US8703172B2 (en) | 2003-01-20 | 2014-04-22 | Nederlandse Organizatie voor Toegepastnatuurwetenschappelijk Onderzoek TNO | Sphingolipids for improvement of the composition of the intestinal flora |
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| WO2005094839A1 (en) * | 2004-03-30 | 2005-10-13 | Snow Brand Milk Products Co., Ltd. | Skin conditioning agent |
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| US8920822B2 (en) | 2004-03-30 | 2014-12-30 | Megmilk Snow Brand Co., Ltd. | Skin beautifier |
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| US20100048493A1 (en) * | 2004-05-07 | 2010-02-25 | Snow Brand Milk Products Co., Ltd. | Method of administering oral flora-improving agent, antibacterial agent and growth promoter |
| AU2005239926B2 (en) * | 2004-05-07 | 2011-03-17 | Megmilk Snow Brand Co., Ltd. | Oral flora-improving agent, antibacterial agent and growth promoter |
| US8183215B2 (en) * | 2004-05-07 | 2012-05-22 | Megmilk Snow Brand Co., Ltd. | Method of administering oral flora-improving agent, antibacterial agent and growth promoter |
| WO2005107769A1 (en) * | 2004-05-07 | 2005-11-17 | Snow Brand Milk Products Co., Ltd. | Oral flora-improving agent, antibacterial agent and growth promoter |
| US7906488B2 (en) | 2004-11-30 | 2011-03-15 | Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno | Sphingolipids in treatment and prevention of steatosis and of steatosis or of hepatotoxicity and its sequelae |
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| JP2007112793A (en) * | 2005-09-22 | 2007-05-10 | Snow Brand Milk Prod Co Ltd | Sphingomyelin-containing medicine, food and drink or fodder |
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| US8486916B2 (en) | 2005-09-22 | 2013-07-16 | Megmilk Snow Brand Co., Ltd. | Medicine, food and drink or feed containing sphingomyelin |
| AU2006293026B2 (en) * | 2005-09-22 | 2012-08-16 | Megmilk Snow Brand Co., Ltd. | Medicine, food and drink or feed containing sphingomyelin |
| JP2012167104A (en) * | 2005-09-22 | 2012-09-06 | Snow Brand Milk Products Co Ltd | Sphingomyelin-containing medicine |
| JP2007246404A (en) * | 2006-03-14 | 2007-09-27 | Snow Brand Milk Prod Co Ltd | Learning ability-improving agent |
| US8440645B2 (en) | 2008-07-31 | 2013-05-14 | Kao Corporation | Ceramide production promoter |
| WO2010020165A1 (en) | 2008-08-18 | 2010-02-25 | 复旦大学附属中山医院 | Promotors of ceramide’s generation |
| US10610561B2 (en) | 2008-08-18 | 2020-04-07 | Zhongshan Hospital of Fudan University | Ceramide production-accelerating agent |
| WO2011043212A1 (en) | 2009-10-05 | 2011-04-14 | 花王株式会社 | Ceramide production enhancer and moisturizing agent |
| WO2013162366A1 (en) * | 2012-04-27 | 2013-10-31 | Stichting Vu-Vumc | Protection of materials by sphingosine based compounds |
| JP2015516982A (en) * | 2012-04-27 | 2015-06-18 | スティッチング フェーウー—フェーウーエムセー | Protection of materials by sphingosine compounds |
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| WO2014034802A1 (en) | 2012-08-29 | 2014-03-06 | 花王株式会社 | Transglutaminase activator |
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