JPH0137377B2 - - Google Patents
Info
- Publication number
- JPH0137377B2 JPH0137377B2 JP14914683A JP14914683A JPH0137377B2 JP H0137377 B2 JPH0137377 B2 JP H0137377B2 JP 14914683 A JP14914683 A JP 14914683A JP 14914683 A JP14914683 A JP 14914683A JP H0137377 B2 JPH0137377 B2 JP H0137377B2
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- combination
- blood
- effect
- alloxan
- 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.)
- Expired
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- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 20
- 239000008280 blood Substances 0.000 claims description 17
- 210000004369 blood Anatomy 0.000 claims description 17
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 15
- 229930003427 Vitamin E Natural products 0.000 claims description 10
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 10
- 239000011709 vitamin E Substances 0.000 claims description 10
- 229940046009 vitamin E Drugs 0.000 claims description 10
- 235000019165 vitamin E Nutrition 0.000 claims description 10
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims description 7
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 6
- 229930003268 Vitamin C Natural products 0.000 claims description 6
- 235000019154 vitamin C Nutrition 0.000 claims description 6
- 239000011718 vitamin C Substances 0.000 claims description 6
- 239000003524 antilipemic agent Substances 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 2
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 26
- 230000000694 effects Effects 0.000 description 20
- 229940088594 vitamin Drugs 0.000 description 19
- 229930003231 vitamin Natural products 0.000 description 19
- 235000013343 vitamin Nutrition 0.000 description 19
- 239000011782 vitamin Substances 0.000 description 19
- 150000003722 vitamin derivatives Chemical class 0.000 description 19
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 16
- 229940079593 drug Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 8
- -1 lipid peroxide Chemical class 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 7
- 235000012000 cholesterol Nutrition 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 4
- 150000003626 triacylglycerols Chemical class 0.000 description 4
- 235000019156 vitamin B Nutrition 0.000 description 4
- 239000011720 vitamin B Substances 0.000 description 4
- MJNIWUJSIGSWKK-BBANNHEPSA-N Riboflavin butyrate Chemical compound CCCC(=O)OC[C@@H](OC(=O)CCC)[C@@H](OC(=O)CCC)[C@@H](OC(=O)CCC)CN1C2=CC(C)=C(C)C=C2N=C2C1=NC(=O)NC2=O MJNIWUJSIGSWKK-BBANNHEPSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229940042585 tocopherol acetate Drugs 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000219823 Medicago Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229920006184 cellulose methylcellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000001278 effect on cholesterol Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 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
- 239000007787 solid Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
Description
【発明の詳細な説明】
本発明は有効成分として、ビタミンB2，ビタ
ミンＣおよびビタミンＥを含有するビタミン配合
剤からなる血中脂質低下剤に関するものである。
近年、過酸化脂質は、動脈硬化、脳卒中、心筋
梗塞、糖尿病、老化などの成人病と密接な関係を
有するものとして注目をあびている。一方、コレ
ステロールやトリグリセライドは従来からこれら
の疾病の危険因子の１つとされている。本発明者
等は、血中脂質低下剤の開発を目的として鋭意研
究を進めた結果、ビタミンB2、ビタミンＣおよ
びビタミンＥからなる配合剤が著明な脂質低下作
用すなわち、血中過酸化脂質、トリグリセライド
およびコレステロール低下作用を有することを見
い出し、本発明を完成するに至つた。
以下に、本発明のビタミン配合剤の血中脂質低
下作用に関する薬理試験について説明する。
試験方法
雄性マウス８週令を用いた。18時間の絶食後ア
ロキサン75mg／Kgを尾静脈から注入した。薬物は
アロキサン投与30分前、24時間後、30時間後の３
回経口投入した。採血は頚部切断にて行なつた。
アロキサン投与48時間後である。採血量は100μ
または200μ。それを生理食塩液にて10倍ま
たは20倍に希釈して、遠心分離（3000rpm，10
分）し、脂質量を測定した。
過酸化脂質は八木法〔K.Yagi：Biochem.Med.
15，212−216（1976）〕に準じ、TBA（チオバルビ
ツール酸）反応物質として測定した。コレステロ
ール、トリグリセライドは酵素法にて測定した。
コレステロールはデタミナ−
TC（協和メデイツ
クス）キツトを、トリグリセライドはトリグリセ
ライド測定試薬（GPO−ｐ−クロルフエノール
発色法）（和光純薬）キツトを使用した。
使用した薬物は、ビタミンB2（酪酸リボフラビ
ン）、ビタミンＣ（アスコルビン酸）およびビタミ
ンＥ（酢酸ｄ−α−トコフエロール）である。
試験結果
〔Ａ〕 アロキサンによる血中脂質の変化
アロキサンを75mg／Kg、静脈投写すると、48時
間後には過酸化脂質とトリグリセライドは５〜７
倍と著明に上昇した。コレステロールはそれ程著
明ではないが、有意に上昇した。
その結果を第１図に示す。
〔Ｂ〕 ビタミン合剤と各単剤の作用
以上のごとく、アロキサン投与48時間後には、
血中脂質が著しく上昇するので、本発明のビタミ
ン合剤と各単剤が、それらに対してどのような作
用を示すかを検討した。ビタミン合剤はビタミン
B2（５mg／Kg）、ビタミンＣ（150mg／Kg）および
ビタミンＥ（50mg／Kg）並びにその２倍量を用い、
それに相当する単剤の効果を求めた。
（Ｂ−１） 血中過酸化脂質におよぼす作用
ビタミンB2，ＣおよびＥ合剤は用量依存的に
有意に血中過酸化脂質を低下した。しかしV.B2
の５，10mg／KgとV.Cの150，300mg／Kgの投与
は、いずれも全く低下しなかつた。V.Eは50mg／
Kgにおいて低下傾向を示し、100mg／Kgでは上記
のビタミン合剤よりは弱いが、有意に低下した。
なお、合剤と各単剤の作用との間には、すべて有
意差が認められた。
その結果を第２図および第５図に示す。
なお、第２乃至４図は対照群を100％として表
現し、本発明のビタミン合剤と各単剤を比較した
ものである。また第５図は絶対値で表現し、上記
ビタミン合剤と各単剤のうちで最も作用のみられ
たビタミンＥとを同時に比較した図である。
（Ｂ−２） 血中トリグリセライドにおよぼす作
用
ビタミンB2，ＣおよびＥの合剤は低用量にお
いて、血中トリグリセライドを低下する傾向を示
し、高用量において有意に低下した。しかし、
V.B2，V.C，V.Eの各単剤は、すべて有意な作用
を有しなかつた。なお、上記ビタミン合剤と各単
剤との間には、すべて有意差が認められた。
その結果を第３図および第５図に示す。
（Ｂ−３） 血中コレステロールにおよぼす作用
血中コレステロールの場合もトリグリセライド
と同様に、ビタミンB2，ＣおよびＥ合剤の高用
量において有意な低下作用が認められ、各単剤に
は有意な作用が認められなかつた。また、上記ビ
タミン合剤と各単剤の作用との間には、すべて有
意差があつた。
その結果を第４図および第５図に示す。
上記の試験例で認められたように、ビタミン
B2，ＣおよびＥ合剤がアロキサンによつて上昇
された血中過酸化脂質を顕著に抑制することを認
めた。また、過酸化脂質と同様に動脈硬化の危険
因子とされているコレステロールやトリグリセラ
イドに対しても用量依存的な低下作用を示すこと
を証明した。一方、ビタミンB2とビタミンＣは
過酸化脂質、トリグリセライドおよびコレステロ
ールのいずれに対しても全く抑制せず、むしろ増
加傾向を示した。ビタミンＥは過酸化脂質を除い
て（これもビタミン合剤の方が強力）有意作用を
示さなかつた。従つて本発明のビタミン合剤の脂
質低下作用は、各単剤の単なる相加作用ではな
く、相乗効果によることが示唆された。
以上説明したように、本発明のビタミン配合剤
は血中脂質低下剤として有用であり、通常の処方
によつて経口的に投与することができ、錠剤、顆
粒剤、カプセル剤、散剤または液剤などの医薬用
製剤として用いられる。
その投与量は患者の症状、年令などによつて異
なるが、通常、成人に対する１回投与量は、配合
剤におけるビタミンB2として10mg乃至30mg、ビ
タミンＣとして300mg乃至900mg、ビタミンＥとし
て100mg乃至300mgであり、１日１回または症状に
応じてそれ以上投与することもできる。また、本
剤と他剤、例えば循環系薬剤との併用も可能であ
る。
次に製剤例をあげて説明を加える。
製剤例
(1) ビタミン合剤（単位投与量）の組成
ビタミンB2（酪酸リボフラビン） 10mg
ビタミンＣ（アスコルビン酸） 300mg
ビタミンＥ（酢酸ｄ−α−トコフエロール）
100mg
(2) 製法
本製剤は公知の固形製剤の製法に準じて製せら
れる。すなわち、主剤及び必要に応じて結晶セル
ロース、カルボキシメチルセルロース等の崩壊
剤、白糖、乳糖、デンプン等の賦形剤及び／また
は軽質無水ケイ酸、デンプン、結晶セルロース等
の吸着剤等の混合末にヒドロキシプロピルセルロ
ース等の水性結合剤を加え公知の方法により細粒
剤又は顆粒剤とする。
更に、上記成分に崩壊剤及び／またはステアリ
ン酸等の滑沢剤を加え公知の方法により錠剤とす
ることができる。上記製剤には矯臭剤として香料
を必要に応じて添加できる。
別に適当な界面活性剤でビタミンＥ、酪酸リボ
フラビンを可溶化し、次いでアスコルビンを溶解
し、クエン酸ナトリウムなどの有機酸ナトリウム
又は水酸化ナトリウムなどのPH調整剤でPHを調整
し、白糖などの矯味剤を添加して液剤とすること
もできる。 DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a blood lipid lowering agent comprising a vitamin combination preparation containing vitamin B 2 , vitamin C and vitamin E as active ingredients. In recent years, lipid peroxide has attracted attention as it is closely related to adult diseases such as arteriosclerosis, stroke, myocardial infarction, diabetes, and aging. On the other hand, cholesterol and triglycerides have been considered to be one of the risk factors for these diseases. As a result of intensive research aimed at developing a blood lipid-lowering agent, the present inventors found that a combination preparation consisting of vitamin B 2 , vitamin C, and vitamin E has a remarkable lipid-lowering effect, that is, blood peroxide lipids. , triglyceride and cholesterol lowering effects, and have completed the present invention. Below, pharmacological tests regarding the blood lipid-lowering effect of the vitamin combination preparation of the present invention will be explained. Test method Eight-week old male mice were used. After fasting for 18 hours, alloxan 75 mg/Kg was injected through the tail vein. The drug was administered 30 minutes before, 24 hours after, and 30 hours after alloxan administration.
It was given orally. Blood was collected by cutting the neck.
This was 48 hours after alloxan administration. Blood sampling amount is 100μ
or 200μ. It was diluted 10 or 20 times with physiological saline and centrifuged (3000 rpm, 10 times).
minutes) and the amount of lipids was measured. Lipid peroxide is determined by the Yagi method [K.Yagi: Biochem.Med.
15, 212-216 (1976)] as a TBA (thiobarbituric acid) reactant. Cholesterol and triglyceride were measured using an enzymatic method.
For cholesterol, a Determiner TC (Kyowa Medics) kit was used, and for triglyceride, a triglyceride measurement reagent (GPO-p-chlorophenol color method) (Wako Pure Chemical Industries) kit was used. The drugs used were vitamin B 2 (riboflavin butyrate), vitamin C (ascorbic acid) and vitamin E (d-α-tocopherol acetate). Test results [A] Changes in blood lipids due to alloxan When 75 mg/Kg of alloxan is administered intravenously, lipid peroxide and triglyceride levels are 5 to 7 after 48 hours.
It has increased markedly by double. Cholesterol was significantly elevated, although not as markedly. The results are shown in FIG. [B] Effects of vitamin combination and each single drug As mentioned above, 48 hours after alloxan administration,
Since blood lipids are markedly elevated, we investigated the effects of the vitamin combination of the present invention and each single agent on these. Vitamin mixture is vitamin
Using B 2 (5 mg/Kg), vitamin C (150 mg/Kg) and vitamin E (50 mg/Kg) and double the amount,
The corresponding effect of a single drug was determined. (B-1) Effect on blood lipid peroxide The combination of vitamins B 2 , C and E significantly lowered blood peroxide in a dose-dependent manner. But VB 2
Administration of 5 and 10 mg/Kg of VC and 150 and 300 mg/Kg of VC did not result in any decrease at all. VE is 50mg/
It showed a decreasing tendency in Kg, and at 100 mg/Kg, it decreased significantly, although it was weaker than the above vitamin combination.
In addition, significant differences were observed between the effects of the combination drug and each single drug. The results are shown in FIGS. 2 and 5. In addition, FIGS. 2 to 4 express the control group as 100% and compare the vitamin combination of the present invention with each single agent. Furthermore, FIG. 5 is a diagram that simultaneously compares the above vitamin mixture and vitamin E, which was the most effective of each single drug, expressed in absolute values. (B-2) Effect on blood triglycerides The combination of vitamins B 2 , C and E showed a tendency to lower blood triglycerides at low doses, and significantly decreased at high doses. but,
Single agents VB 2 , VC, and VE all had no significant effect. In addition, all significant differences were observed between the above vitamin combination and each single drug. The results are shown in FIGS. 3 and 5. (B-3) Effect on blood cholesterol As with triglycerides, a significant lowering effect on blood cholesterol was observed at high doses of the combination of vitamins B 2 , C and E, and each single agent had a significant lowering effect. No effect was observed. Furthermore, there were all significant differences between the effects of the above vitamin combinations and each single agent. The results are shown in FIGS. 4 and 5. As observed in the test example above, vitamin
It was found that the combination of B 2 , C and E significantly inhibited the increase in blood peroxidized lipids caused by alloxan. Furthermore, it was demonstrated that, like lipid peroxide, it also showed a dose-dependent lowering effect on cholesterol and triglyceride, which are considered risk factors for arteriosclerosis. On the other hand, vitamin B 2 and vitamin C did not inhibit lipid peroxide, triglyceride, or cholesterol at all, but rather showed an increasing tendency. Vitamin E had no significant effect except on lipid peroxide (also the vitamin combination was more potent). Therefore, it was suggested that the lipid-lowering effect of the vitamin combination of the present invention is due to a synergistic effect, rather than simply an additive effect of each single agent. As explained above, the vitamin combination preparation of the present invention is useful as a blood lipid-lowering agent, and can be administered orally according to a conventional prescription, and can be administered in the form of tablets, granules, capsules, powders, or liquids. It is used as a pharmaceutical preparation. The dosage varies depending on the patient's symptoms, age, etc., but the usual dosage for adults is 10mg to 30mg of vitamin B2 , 300mg to 900mg of vitamin C, and 100mg to 100mg of vitamin E. The dose is 300 mg, and it can be administered once a day or more depending on the symptoms. Furthermore, it is also possible to use this drug in combination with other drugs, such as circulatory system drugs. Next, an explanation will be given by giving examples of formulations. Formulation example (1) Composition of vitamin combination (unit dose) Vitamin B 2 (riboflavin butyrate) 10 mg Vitamin C (ascorbic acid) 300 mg Vitamin E (d-α-tocopherol acetate)
100mg (2) Manufacturing method This preparation is manufactured according to a known manufacturing method for solid preparations. That is, hydroxyl is added to a mixed powder of the base agent and, if necessary, a disintegrant such as crystalline cellulose or carboxymethyl cellulose, an excipient such as white sugar, lactose, or starch, and/or an adsorbent such as light silicic anhydride, starch, or crystalline cellulose. An aqueous binder such as propyl cellulose is added to form fine granules or granules by a known method. Furthermore, a disintegrant and/or a lubricant such as stearic acid may be added to the above ingredients to form a tablet by a known method. A fragrance can be added to the above preparation as a flavoring agent, if necessary. Separately, vitamin E and riboflavin butyrate are solubilized with a suitable surfactant, then ascorbin is dissolved, the pH is adjusted with a pH adjusting agent such as organic acid sodium such as sodium citrate or sodium hydroxide, and flavoring such as white sugar is added. It is also possible to prepare a liquid by adding an agent.
第１図はアロキサン投与48時間後の血中脂質の
変化を示すグラフである。縦軸の数値は平均値±
標準誤差を表わし、＊はＰ（有意差危険率、以下
同じ）＜0.05、＊＊はＰ＜0.01、＊＊＊はＰ＜
0.001を示す。第２図はアロキサン誘発高過酸化
脂質血症におよすビタミンB2，ＣおよびＥ合剤
の作用を表示した図である。Ｂ図はＡ図の２倍用
量の場合を表わす。縦軸は対照群の値を100％と
した時の値である（以下、第３および４図も同
様）。＊＊はＰ＜0.01、＊＊＊はＰ＜0.001を示
す。第３図には、アロキサン誘発高トリグリセラ
イド血症におよぼす上記ビタミン合剤の作用を示
した。＊＊＊はＰ＜0.001を示す。第４図はアロ
キサン誘発高コレステロール血症におよぼす上記
ビタミン合剤の作用を表わし、＊＊＊はＰ＜
0.001を示す。第５図はアロキサン誘発高脂血症
におよぼす上記ビタミン合剤の作用を表わしたも
のである。正常値はアロキサン静注の代わりに生
理食塩水を静注した正常マウスの測定値を示す。
縦軸の数値は平均値±標準誤差を表わし、＊＊は
Ｐ＜0.01、＊＊＊はＰ＜0.001を示す。
FIG. 1 is a graph showing changes in blood lipids 48 hours after alloxan administration. Values on the vertical axis are mean ±
Standard error is shown, * is P (significant difference risk ratio, same below) < 0.05, ** is P < 0.01, *** is P <
Shows 0.001. FIG. 2 is a diagram showing the effects of a combination of vitamins B 2 , C and E on alloxan-induced hyperlipidemia. Figure B represents the double dose of Figure A. The vertical axis is the value when the value of the control group is taken as 100% (the same applies to Figures 3 and 4 below). ** indicates P<0.01, *** indicates P<0.001. FIG. 3 shows the effect of the above vitamin combination on alloxan-induced hypertriglyceridemia. *** indicates P<0.001. Figure 4 shows the effect of the above vitamin combination on alloxan-induced hypercholesterolemia, and *** indicates P<
Shows 0.001. FIG. 5 shows the effect of the above vitamin combination on alloxan-induced hyperlipidemia. The normal value indicates the value measured in a normal mouse in which physiological saline was intravenously injected instead of alloxan intravenously.
The numerical value on the vertical axis represents the mean value ± standard error, ** indicates P<0.01, and *** indicates P<0.001.
Claims (1)
およびビタミンＥを含有する血中脂質低下剤。1 Active ingredients include vitamin B 2 and vitamin C.
and a blood lipid lowering agent containing vitamin E.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14914683A JPS6041611A (en) | 1983-08-17 | 1983-08-17 | Blood lipid improving agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14914683A JPS6041611A (en) | 1983-08-17 | 1983-08-17 | Blood lipid improving agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6041611A JPS6041611A (en) | 1985-03-05 |
| JPH0137377B2 true JPH0137377B2 (en) | 1989-08-07 |
Family
ID=15468773
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14914683A Granted JPS6041611A (en) | 1983-08-17 | 1983-08-17 | Blood lipid improving agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6041611A (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2547400B2 (en) * | 1986-02-27 | 1996-10-23 | 昭和電工株式会社 | Veterinary drug |
| JP3283274B2 (en) * | 1991-06-15 | 2002-05-20 | サントリー株式会社 | New composition |
| US6916849B2 (en) | 2000-10-23 | 2005-07-12 | Sankyo Company, Limited | Compositions for improving lipid content in the blood |
| AU2001295991A1 (en) * | 2000-10-23 | 2002-05-06 | Sankyo Company Limited | Compositions for improving lipids in blood |
| CN1240379C (en) | 2000-11-07 | 2006-02-08 | 三共株式会社 | Lipid peroxide-lowering compositions |
| WO2002047683A1 (en) * | 2000-12-14 | 2002-06-20 | Sankyo Company, Limited | Blood lipid ameliorant composition |
| CA2433285C (en) | 2000-12-14 | 2009-06-23 | Sankyo Company, Limited | Blood lipid ameliorating composition |
| US7037934B2 (en) | 2000-12-14 | 2006-05-02 | Sankyo Company, Limited | Blood lipid ameliorant composition |
| TWI284529B (en) * | 2000-12-18 | 2007-08-01 | Sankyo Co | A composition for lowering triglyceride |
| EP1553099A4 (en) * | 2002-08-02 | 2006-06-28 | Inst Radiation Med Amms Pla | A riboflavin derivative and its manufacture and uses |
-
1983
- 1983-08-17 JP JP14914683A patent/JPS6041611A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6041611A (en) | 1985-03-05 |
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