JP2000080043A - Water-soluble vitamin k agent - Google Patents
Water-soluble vitamin k agentInfo
- Publication number
- JP2000080043A JP2000080043A JP10285841A JP28584198A JP2000080043A JP 2000080043 A JP2000080043 A JP 2000080043A JP 10285841 A JP10285841 A JP 10285841A JP 28584198 A JP28584198 A JP 28584198A JP 2000080043 A JP2000080043 A JP 2000080043A
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- water
- soluble vitamin
- agent
- blood
- 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
- 229940046010 vitamin k Drugs 0.000 title claims abstract description 36
- 239000003795 chemical substances by application Substances 0.000 title abstract 3
- 150000003721 vitamin K derivatives Chemical class 0.000 claims abstract description 36
- 229930003448 Vitamin K Natural products 0.000 claims abstract description 35
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000011712 vitamin K Substances 0.000 claims abstract description 35
- 235000019168 vitamin K Nutrition 0.000 claims abstract description 35
- 235000013305 food Nutrition 0.000 claims abstract description 14
- 239000000463 material Substances 0.000 claims abstract description 9
- 244000063299 Bacillus subtilis Species 0.000 claims abstract description 5
- 235000014469 Bacillus subtilis Nutrition 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 4
- 239000008280 blood Substances 0.000 abstract description 14
- 210000004369 blood Anatomy 0.000 abstract description 14
- 239000003814 drug Substances 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 7
- 208000001132 Osteoporosis Diseases 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract 1
- 235000013557 nattō Nutrition 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 4
- PFRQBZFETXBLTP-UHFFFAOYSA-N Vitamin K2 Natural products C1=CC=C2C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C(=O)C2=C1 PFRQBZFETXBLTP-UHFFFAOYSA-N 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 2
- 108010094028 Prothrombin Proteins 0.000 description 2
- 102100027378 Prothrombin Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108010000499 Thromboplastin Proteins 0.000 description 2
- 102000002262 Thromboplastin Human genes 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 235000009491 menaquinone-4 Nutrition 0.000 description 2
- 239000011676 menaquinone-4 Substances 0.000 description 2
- DKHGMERMDICWDU-GHDNBGIDSA-N menaquinone-4 Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 DKHGMERMDICWDU-GHDNBGIDSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229940039716 prothrombin Drugs 0.000 description 2
- PFRQBZFETXBLTP-RCIYGOBDSA-N 2-[(2e,6e,10e,14e,18e)-3,7,11,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaen-1-yl]-3-methyl-1,4-dihydronaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 PFRQBZFETXBLTP-RCIYGOBDSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 101800004937 Protein C Proteins 0.000 description 1
- 102100036546 Salivary acidic proline-rich phosphoprotein 1/2 Human genes 0.000 description 1
- 101800001700 Saposin-D Proteins 0.000 description 1
- 238000004159 blood analysis Methods 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 235000021107 fermented food Nutrition 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 235000009464 menaquinone-7 Nutrition 0.000 description 1
- 239000011700 menaquinone-7 Substances 0.000 description 1
- RAKQPZMEYJZGPI-LJWNYQGCSA-N menaquinone-7 Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 RAKQPZMEYJZGPI-LJWNYQGCSA-N 0.000 description 1
- 229960005481 menatetrenone Drugs 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 239000011772 phylloquinone Substances 0.000 description 1
- MBWXNTAXLNYFJB-LKUDQCMESA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCCC(C)CCCC(C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-LKUDQCMESA-N 0.000 description 1
- -1 phytoquinone (PK) Natural products 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本研究は、最近骨粗鬆症を予
防する効果が期待できることで注目されているビタミン
Ｋの血中濃度を，口から摂取することによって効率よく
高め、しかもそれを長時間持続することのできる医薬品
あるいは食品素材に関する。BACKGROUND OF THE INVENTION The present study aims to efficiently increase the concentration of vitamin K in the blood by ingesting it through the mouth and to maintain it for a long period of time, which has recently attracted attention because of its expected effect of preventing osteoporosis. Pharmaceutical or food materials that can be used.
【０００２】[0002]
【従来の技術】ビタミンＫは、従来、血液が凝固する際
必要な因子として知られているが、その必要量は極微量
であり、一般に成人では腸内細菌から供給されるので欠
乏症が出ることは少なく、あまり注目されることがなか
った。2. Description of the Related Art Vitamin K is conventionally known as a necessary factor when blood coagulates, but the necessary amount is extremely small. In general, in adults, deficiency occurs because it is supplied from intestinal bacteria. Were few and did not receive much attention.
【０００３】しかし、最近の研究で、ビタミンＫは骨形
成促進作用と骨吸収抑制作用があり、ビタミンＫの投与
で骨密度が増加することが明らかにされた。However, recent studies have shown that vitamin K has a bone formation promoting effect and a bone resorption suppressing effect, and that administration of vitamin K increases bone density.
【０００４】そして、骨粗鬆症患者の血中濃度は健常人
に比べて約１／２と少ないこと、また合成ビタミンＫが
骨粗鬆症治療薬として臨床試験も行われ、１日４５ｍｇ
以上の投与で治療効果のあることなどが証明されてい
る。しかし骨粗鬆症は発病してからの治療より予防が重
要であり、このためには食品から日常的にビタミンＫを
摂取することが望まれる。[0004] The blood concentration of osteoporosis patients is as low as about 1/2 that of healthy individuals, and synthetic vitamin K is also used as a therapeutic agent for osteoporosis in clinical trials.
It has been proven that the above administrations have therapeutic effects. However, prevention of osteoporosis is more important than treatment after the onset of illness. For this purpose, it is desired to take vitamin K from foods on a daily basis.
【０００５】日常のビタミン摂取は食品を通じて行われ
るのが望ましく、上記ビタミンＫは、緑黄色野菜や海草
類にビタミンＫ１、納豆などの発酵食品にビタミンＫ２
の含有が知られているので、これらの食品を食べること
でビタミンＫの摂取を図ることが一応できる。しかし、
普通のビタミンＫの血中での半減期は短く、従ってしょ
っちゅう食べる必要があった。また、このような食品の
うちでビタミンＫの含量が最も高いのは納豆であるが、
それでも一度にかなりの量を食べなければならないた
め、特に独特の臭いが嫌いな者には続けて摂取すること
が困難であった。[0005] It is desirable that daily vitamin intake is carried out through foods. The above-mentioned vitamin K is obtained from vitamin K 1 in green-yellow vegetables and seaweeds, and from vitamin K 2 in fermented foods such as natto.
It is known that eating these foods makes it possible to obtain vitamin K. But,
The half-life of normal vitamin K in the blood was short, so it was necessary to eat often. Natto has the highest content of vitamin K among such foods,
Nevertheless, since a large amount of food must be eaten at a time, it is difficult for those who do not like the peculiar smell to take it continuously.
【０００６】[0006]
【発明が解決しようとする課題】従って、本発明は容易
に摂取できて、長時間血中のビタミンＫ濃度を必要な濃
度に高めたままそれを維持する効果を有し、なおかつ安
全性にも優れた医薬品、あるいは食品素材を提供するこ
とを目的とする。Therefore, the present invention can be easily ingested, has the effect of maintaining the vitamin K concentration in blood for a long time at a required concentration and maintaining it, and is also safe. The purpose is to provide excellent pharmaceuticals or food materials.
【０００７】[0007]
【課題を解決するための手段】本発明は、このような事
情に鑑みて長年納豆の成分の研究（Ｅｘｐｅｒｉｅｎｔ
ｉａ，４３：１１１０，１９８７；Ａｃｔａ Ｈａｅｍ
ａｔｏｌ．，８４：１３９，１９９０；Ｆｉｂｒｉｎｏ
ｌｙｓｉｓ，６：８６，１９９２；日本薬剤師会誌、３
０：７３，１９９４；バイオインダストリー、１４：４
７，１９９６）、あるいは納豆菌中及び血中ビタミンＫ
の分析（日本血栓止血誌、８：２８７，１９９７；１４
ｔｈ Ｉｎｔ．Ｃｏｎｇ．Ｆｉｂｒｉｎｏｌｙｓｉｓ
＆ Ｔｈｒｏｍｂｏｌｙｓｉｓ，Ｓｌｏｖｅｎｉａ，発
表、１９９８）に鋭意努力してきた結果、今回初めて納
豆とかオカラ納豆など納豆菌による発酵物が持つ水溶性
のビタミンＫ分画が臭いもネバリも少なくて摂取しやす
く、しかもそれを１回摂取することによって高い血中ビ
タミンＫ濃度を維持できることを明らかにし、これに基
づき本発明を完成するに至った。なお、これまで水溶性
ビタミンＫの経口摂取に関しての研究は全くなく、今回
が初めてのことである。即ち、本発明は納豆菌発酵物か
ら得た水溶性ビタミンＫ分画をそれ単独、あるいは他と
の混合物の形で含有させることを特徴とする経口用医薬
品あるいは食品素材に関する。SUMMARY OF THE INVENTION In view of such circumstances, the present invention has long studied the components of natto (Expertient).
ia, 43: 1110, 1987; Acta Haem
atol. , 84: 139, 1990; Fibrino.
lysis, 6:86, 1992; Japanese Journal of Pharmacists, 3
0:73, 1994; Bioindustry, 14: 4.
7, 1996), or vitamin K in natto and blood
Analysis (Japan Thrombus Hemostasis, 8: 287, 1997; 14)
th Int. Cong. Fibrinolysis
& Thrombolysis, Slovenia, 1998) as a result of our hard work, this time for the first time, the water-soluble Vitamin K fraction of fermented products of Bacillus natto such as natto or okara natto has little odor and slime and is easy to take. It has been clarified that a single ingestion of the compound can maintain a high blood vitamin K concentration, and based on this, the present invention has been completed. There is no study on oral intake of water-soluble vitamin K, and this is the first time. That is, the present invention relates to an oral drug or a food material characterized by containing a water-soluble vitamin K fraction obtained from a fermented product of Bacillus natto alone or in the form of a mixture with another.
【０００８】[0008]
【発明の実施の形態】以下、実施例を用いて本発明を具
体的に説明する。DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be specifically described with reference to examples.
【０００９】第１例 一般の大豆納豆の発酵過程で、生じたビタミンＫ（ＭＫ
−７）は出願人がこれまで開発してきた高速液体クロマ
トグラフィー（ＨＰＬＣ）による方法（須見ら、日本血
栓止血誌、８：２８７、１９９７）で分析した結果、宮
城野菌が最も強く、３７℃、１日目で重量（ｗｅｔ）１
００ｇ当たり１，７３０μｇに達した。オカラを原料と
しても、同じ発酵条件下で両活性はほぼ相関すること、
ビタミンＫとしてはフィロキノン（ＰＫ）、メナキノン
−４（ＭＫ−４）でなくメナキノン−７（ＭＫ−７）の
著しく増加すること（２日目、約２００μｇ／１００ｇ
ｗｅｔ ｗｔ．）、また生産されたＭＫ−７の約５０％
は水可溶分画にくることが分かった。そこでメンブラン
フィルター処理及び凍結乾燥したこの水可溶性ビタミン
Ｋ（１，０００μｇ／９．３ｇ ｄｒｙ ｗｔ．）を６
人の健常ボランティアに経口投与し、経時的に血中ＭＫ
−７濃度を調べた結果、投与前に比べて５０倍以上（４
〜６時間目、５３．３±１２．０ｎｇ／ｍｌ血漿）に増
加すること、またその効果は同量の純ＭＫ７（＞９５
％）を投与した場合（２時間目、６４．８±１１．２ｎ
ｇ／ｍｌ血漿）に比べてはるかに長時間持続することが
分かった。なお、今回の条件下ではいずれもトロンボエ
ラストグラフィーあるいはプロトロンビン時間、活性部
分トロンボプラスチン時間などでみた血液凝固−線溶系
の影響は認められなかった。First Example Vitamin K (MK) produced in the fermentation process of general soybean natto
-7) was analyzed by a method using high performance liquid chromatography (HPLC) (Sumi et al., Japanese Journal of Thrombosis and Hemostasis, 8: 287, 1997) which has been developed by the applicant. Day 1 weight (wet) 1
It reached 1,730 μg per 00 g. Even if okara is used as a raw material, both activities are almost correlated under the same fermentation conditions,
As vitamin K, phytoquinone (PK), menaquinone-7 (MK-7) but not menaquinone-4 (MK-4) increased remarkably (about 200 μg / 100 g on the second day)
wet wt. ) And about 50% of the MK-7 produced
Was found to be in the water soluble fraction. Then, 6 parts of this water-soluble vitamin K (1,000 μg / 9.3 g dry wt.), Which had been treated with a membrane filter and lyophilized,
Oral administration to healthy human volunteers and blood MK
As a result of examining the -7 concentration, it was found to be 50 times or more (4
~ 6 hours, 53.3 ± 12.0 ng / ml plasma), and the effect was similar to that of pure MK7 (> 95
%) (24.8 hours, 64.8 ± 11.2 n)
g / ml of plasma). Under these conditions, no influence of the blood coagulation-fibrinolysis system was observed in any of thromboelastography, prothrombin time, active partial thromboplastin time and the like.
【００１０】第２例 １ｋｇの市販納豆（くき食品株式会社、福岡）に対し
て、５１の蒸留水を加え、静かに撹拌、静置した後、ガ
ーゼ濾過及び３，０００ｒｐｍ、１０分間の遠心分離を
行い上清を得た。これを水洗及び０．０１Ｍリン酸緩衝
液、ｐＨ７．４で平衡化したＤＥＡＥ−ｃｅｌｌｕｌｏ
ｓｅカラムにａｐｐｌｙし、同緩衝液で洗浄後、第１例
と同じＨＰＬＣ法で確認されたビタミンＫを含む分画を
０．１〜１．０ＭＮａＣｌを含むリン酸緩衝液でグラジ
ェント溶出して得た。この“水溶性ビタミンＫ”分画を
集めてメンブランフィルター（分子量１万以上）で濃縮
及び水で透析した後、凍結乾燥した。このものはほとん
ど無臭で、水に溶かしてもネバリのない、黄色粉末であ
り、１ｇ当たり約１，０００μｇのＭＫ−７を含んでい
た。この乾燥物そのままを５人の健常成人に、１ｇずつ
朝１０時に経口摂取させた時の経時的な血漿中のビタミ
ンＫ（ＭＫ−７）濃度をほぼ同量の純粋なビタミンＫ
（ＭＫ−７）を摂取させた場合と比較してみた成績が表
１である。いずれの群においても４時間目をピークに、
摂取前に比べて有意な血中ビタミンＫ濃度の冗進が確認
されたが（ｐ＜０．００５）、水溶性ビタミンＫ投与後
の血中ＭＫ−７濃度の充進の方がはるかに持続的で、特
に摂取１６時間以降は純ＭＫ７摂取群に比べて著しい差
（ｐ〈０．００５）のあることが分った。なお、この場
合もトロンボエラストグラフィー、活性部分トロンボプ
ラスチン時間、あるいは血漿プロトロンビン、プロテイ
ンＣ含量などで調べた血液凝固−線溶系の活性に有意の
変化は認められなかった。Second Example To 1 kg of commercially available natto (Kuki Foods Co., Ltd., Fukuoka), 51 distilled water was added, and the mixture was gently stirred and allowed to stand. After that, gauze filtration and centrifugation at 3,000 rpm for 10 minutes were performed. Was performed to obtain a supernatant. This was washed with water and equilibrated with 0.01 M phosphate buffer, pH 7.4, in DEAE-cellulo.
After applying to the se column and washing with the same buffer, the fraction containing vitamin K confirmed by the same HPLC method as in Example 1 was gradient-eluted with a phosphate buffer containing 0.1 to 1.0 M NaCl. Obtained. The "water-soluble vitamin K" fractions were collected, concentrated with a membrane filter (molecular weight 10,000 or more), dialyzed with water, and lyophilized. The product was almost odorless, was a yellow powder which did not give off even when dissolved in water, and contained about 1,000 μg of MK-7 per gram. When the dried product was orally ingested by 1 healthy person at 5 o'clock in the morning at 5 o'clock in the morning, the vitamin K (MK-7) concentration in plasma over time was substantially the same as that of pure vitamin K.
Table 1 shows the results as compared with the case where (MK-7) was taken. Peaking at 4 hours in any group,
Although a significant increase in blood vitamin K concentration was confirmed as compared to before ingestion (p < 0.005), the increase in blood MK-7 concentration after administration of water-soluble vitamin K was much longer. It was found that there was a remarkable difference (p < 0.005) compared with the pure MK7 intake group, especially after 16 hours of ingestion. In this case, no significant change was observed in the activity of the blood coagulation-fibrinolysis system as determined by thromboelastography, active partial thromboplastin time, plasma prothrombin, protein C content and the like.
【表１】 [Table 1]
【００１１】[0011]
【発明の効果】本発明によれば、上記実施例で示したよ
うに、効率よく血中ビタミンＫ濃度を高めることがで
き、また従来の医薬品や食品で摂取されるビタミンＫそ
のものに比べて血中濃度の充進効果をはるかに長時間持
続できることから、骨粗鬆症など種々の生活習慣病予防
目的のより効果的な医薬品あるいは食品素材を提供する
ことができる。According to the present invention, as shown in the above embodiment, the concentration of vitamin K in blood can be efficiently increased, and the blood concentration of vitamin K is higher than that of conventional vitamin K itself taken in medicines and foods. Since the effect of increasing the medium concentration can be maintained for a long time, a more effective drug or food material for preventing various lifestyle-related diseases such as osteoporosis can be provided.
Claims (1)
Ｋ分画をそれ単独、あるいは他との混合物の形で含有さ
せることを特徴とする経口用医薬品あるいは食品素材。1. An oral pharmaceutical or food material comprising a water-soluble vitamin K fraction obtained from a fermented product of Bacillus natto, alone or in a mixture with another.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10285841A JP2000080043A (en) | 1998-09-01 | 1998-09-01 | Water-soluble vitamin k agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10285841A JP2000080043A (en) | 1998-09-01 | 1998-09-01 | Water-soluble vitamin k agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000080043A true JP2000080043A (en) | 2000-03-21 |
Family
ID=17696783
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10285841A Pending JP2000080043A (en) | 1998-09-01 | 1998-09-01 | Water-soluble vitamin k agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2000080043A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009104443A1 (en) | 2008-02-19 | 2009-08-27 | コニカミノルタホールディングス株式会社 | Thin film forming method and thin film stack |
| EP2233607A1 (en) | 2000-12-12 | 2010-09-29 | Konica Corporation | Dielectric coated electrode, and plasma discharge apparatus using the electrode |
| WO2010139690A1 (en) * | 2009-06-03 | 2010-12-09 | Chr. Hansen A/S | Bacteria thya(-) mutants with increased vitamin k |
-
1998
- 1998-09-01 JP JP10285841A patent/JP2000080043A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2233607A1 (en) | 2000-12-12 | 2010-09-29 | Konica Corporation | Dielectric coated electrode, and plasma discharge apparatus using the electrode |
| EP2233605A1 (en) | 2000-12-12 | 2010-09-29 | Konica Corporation | Product comprising a metal oxide layer having a carbon content of from 0.1 to 5 % by weight, and optical film |
| EP2233606A2 (en) | 2000-12-12 | 2010-09-29 | Konica Corporation | Plasma discharge apparatus |
| EP2397576A1 (en) | 2000-12-12 | 2011-12-21 | Konica Corporation | Layer forming method, product comprising the layer, optical film, dielectric-coated electrode and plasma discharge apparatus |
| WO2009104443A1 (en) | 2008-02-19 | 2009-08-27 | コニカミノルタホールディングス株式会社 | Thin film forming method and thin film stack |
| WO2010139690A1 (en) * | 2009-06-03 | 2010-12-09 | Chr. Hansen A/S | Bacteria thya(-) mutants with increased vitamin k |
| JP2012528826A (en) * | 2009-06-03 | 2012-11-15 | セーホーエル．ハンセン アクティーゼルスカブ | Vitamin K-enhanced thyA (-) mutant bacteria |
| US8871195B2 (en) | 2009-06-03 | 2014-10-28 | Chr. Hansen A/S | Bacteria thyA(−) mutants with increased vitamin K |
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