JPH044299B2 - - Google Patents
Info
- Publication number
- JPH044299B2 JPH044299B2 JP57091466A JP9146682A JPH044299B2 JP H044299 B2 JPH044299 B2 JP H044299B2 JP 57091466 A JP57091466 A JP 57091466A JP 9146682 A JP9146682 A JP 9146682A JP H044299 B2 JPH044299 B2 JP H044299B2
- Authority
- JP
- Japan
- Prior art keywords
- fatty acid
- ester
- oil
- monoester
- 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.)
- Expired - Lifetime
Links
- -1 fatty acid ester Chemical class 0.000 claims description 55
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 36
- 229930195729 fatty acid Natural products 0.000 claims description 36
- 239000000194 fatty acid Substances 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 31
- 229930003231 vitamin Natural products 0.000 claims description 23
- 235000013343 vitamin Nutrition 0.000 claims description 23
- 239000011782 vitamin Substances 0.000 claims description 23
- 229940088594 vitamin Drugs 0.000 claims description 23
- 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 13
- 150000004665 fatty acids Chemical class 0.000 claims description 12
- 150000005691 triesters Chemical class 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 9
- 150000005690 diesters Chemical class 0.000 claims description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 235000011187 glycerol Nutrition 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 5
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 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 claims 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 17
- 235000015112 vegetable and seed oil Nutrition 0.000 description 13
- 239000008158 vegetable oil Substances 0.000 description 13
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 11
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 8
- 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 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 229950004959 sorbitan oleate Drugs 0.000 description 6
- 235000019484 Rapeseed oil Nutrition 0.000 description 4
- 239000010497 wheat germ oil Substances 0.000 description 4
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 3
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 3
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 3
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 3
- 239000005642 Oleic acid Substances 0.000 description 3
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 3
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 3
- 229930003427 Vitamin E Natural products 0.000 description 3
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 3
- 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 description 3
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 229950006451 sorbitan laurate Drugs 0.000 description 3
- 235000011067 sorbitan monolaureate Nutrition 0.000 description 3
- 235000019155 vitamin A Nutrition 0.000 description 3
- 239000011719 vitamin A Substances 0.000 description 3
- 235000019165 vitamin E Nutrition 0.000 description 3
- 229940046009 vitamin E Drugs 0.000 description 3
- 239000011709 vitamin E Substances 0.000 description 3
- 229940045997 vitamin a Drugs 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 150000001656 butanoic acid esters Chemical class 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 235000019871 vegetable fat Nutrition 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- 241000345998 Calamus manan Species 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 125000005313 fatty acid group Chemical group 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 235000012950 rattan cane Nutrition 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 229950011392 sorbitan stearate Drugs 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は長期間にわたり澄明な安定性にすぐれ
た脂溶ビタミン配合油溶組成物に関し、詳しくは
２重量％から最高25重量％までのビタミンB2テ
トラ酪酸エステル（以下ビタミンB2酪酸エステ
ルと称す）にと、特定されたグリセリン脂肪酸エ
ステル、ソルビタン脂肪酸エステル、ポリオキシ
エチレンソルビタン脂肪酸エステル、あるいはそ
れらの２種又は３種の混合物を油性可溶化剤とし
て配合した脂溶性ビタミン配合油溶組成物に関す
るものである。
脂肪性ビタミンであるビタミンB2酪酸エステ
ルは近年過酸化脂質の低下、血中HDL−Ｃ、
LDL異常値の改善など臨床上有用視されている。
従来、ビタミンB2酪酸エステルは粉体状にて
錠剤、粒剤、散剤中に加え製剤したり、水性及
び／又は油性懸濁剤中に分散させて製剤してい
た。また、ビタミンB2酪酸エステルの１重量％
位までの少量処方での油溶組成物は、医薬品、食
品などに使用されていたが、多量処方での澄明な
安定性のある油溶組成物は製造が困難であつた。
本発明は上記の欠点を排除したビタミンB2酪
酸エステルを２重量％から最高25重量％まで配合
しうる脂溶ビタミン配合油溶組成物を提供するも
のであり、その要旨とするところはビタミンB2
酪酸エステルに、油性可溶化剤として(a)脂肪酸エ
ステルが、脂肪酸の炭素数６乃至12の脂肪酸のモ
ノエステル、あるいは該モノエステルとジ及び／
又はトリエステルであるグリセリン脂肪酸エステ
ル、(b)脂肪酸エステルが、脂肪酸の炭素数12乃至
18の脂肪酸のモノエステル、あるいは該モノエス
テルとジ及び／又はトリエステルであるソルビタ
ン脂肪酸エステル、(c)脂肪酸エステルが、脂肪酸
の炭素数12乃至18の脂肪酸のモノエステル、ある
いは該モノエステルとジ及び／又はトリエステル
であり、且つ酸化エチレンの付加モル数が２乃至
30であるポリオキシエチレンソルビタン脂肪酸エ
ステル、あるいは(d)上記(a)、(b)及び(c)の２種又は
３種の混合物を配合し、且つその際ビタミンB2
テトラ酪酸エステルの配合率が２〜25重量％であ
ることを特徴とする長期にわたり澄明な脂溶性ビ
タミン配合油溶組成物に存するものである。本発
明によればビタミンB2酪酸エステルを２重量％
から最高25重量％まで多量に配合し得た安定性の
ある油溶組成物が得られ、性状面に於ても濁り及
び結晶の析出などもなく、長期間安定に保存する
ことができる。
本発明による油溶組成物に於てビタミンB2酪
酸エステルに配合する油性可溶化剤としてのグリ
セリン脂肪酸エステルは脂肪酸の炭素数４乃至
18、好ましくは６乃至12の脂肪酸モノエステル、
あるいは該モノエステルとジエステル及び／又は
トリエステル、好ましくはモノエステル40重量％
以上含有の脂肪酸エステルであり、ソルビタン脂
肪酸エステルは脂肪酸の炭素数12乃至18の脂肪酸
モノエステル、あるいは該モノエステルとジエス
テル及び／又はトリエステル、好ましくはモノエ
ステル40重量％以上含有の脂肪酸エステルであ
り、ポリオキシエチレンソルビタン脂肪酸エステ
ルは酸化エチレンの付加モル数が２乃至30、好ま
しくは20、脂肪酸の炭素数12乃至18、好ましくは
18の脂肪酸モノエステル、あるいは該モノエステ
ルとジエステル及び／又はトリエステル、好まし
くはモノエステル40重量％以上含有の脂肪酸エス
テルである。
本発明による油溶組成物は特定のグリセリン脂
肪酸エステル、ソルビタン脂肪酸エステル、ポリ
オキシエチレンソルビタン脂肪酸エステルあるい
はそれらの混合物を配合することにより、油溶組
成物に混加するビタミンB2酪酸エステルの配合
率を従来のものと異なり（従来はその配合率は１
重量％以下）、２重量％から最高25重量％までと
なすことが可能となつたものであり、かかる高配
合率であるにもかかわらず従来全く期待できなか
つた長期間にわたり澄明な安定性のあるものであ
る。
なお、本発明によるビタミンB2酪酸エステル
の配合率が25重量％以上になると目的とする油溶
組成物の調製が困難となり、30重量％以上になる
とその調製が不可能となる。
本発明によるビタミンB2酪酸エステル配合の
油溶組成物には、必要に応じてビタミンＡ，ビタ
ミンＥ、ビタミンＤなどの脂溶性ビタミン類及び
米油、小麦胚芽油、大豆油、綿実油、ナタネ油、
ラツカセイ油などの植物油を混合することもでき
る。
本発明によるビタミンB2酪酸エステル配合油
溶組成物及び該組成物にさらに脂溶性ビタミン類
あるいは植物油を混加した組成物は充填してソフ
トカプセル、ハードカプセルあるいはマイクロカ
プセル剤となすこともできる。
以下に実施例を示し本発明を詳細に説明する
が、本発明は以下の実施例により限定されるもの
ではない。
実施例 １
本発明による油溶組成物を下記の如くにして得
た。すなわちビタミンB2酪酸エステル２，10及
び25重量％と下記に示す(A)〜(G)の油性可溶化剤そ
れぞれ98，90及び75重量％とを配合して本発明に
よる油溶組成物を得、これらの濁度をそれぞれの
濾過精製油を対照としてポイツク積分球式濁度計
により測定し、それにより澄明度の検討を行なつ
た。
(A) ラウリル酸ソルビタンエステル（モノエステ
ル含有量約60％） 100％
(B) オレイン酸ソルビタンエステル・POE（20）
（モノエステル含有量約80％） 100％
(C) カプリル酸グリセリンエステル（モノエステ
ル含有量約55％） 100％
(D) オレイン酸ソルビタンエステル・POE（20）
（モノエステル含有量約80％） 10％
オレイン酸ソルビタンエステル（モノエステル
含有量約90％） 90％
(E) ステアリン酸ソルビタンエステル・POE
（20）（モノエステル含有量約40％） 10％
オレイン酸グリセリンエステル（モノエステル
含有量約40％） 90％
(F) カプリル酸グリセリンエステル（モノエステ
ル含有量約95％） 92％
ラウリル酸ソルビタンエステル（モノエステル
含有量約60％） ８％
(G) ラウリル酸ソルビタンエステル（モノエステ
ル含有量約60％） ８％
オレイン酸ソルビタンエステル・POE（20）
（モノエステル含有量約90％） ７％
カプロン酸グリセリンエステル（モノエステル
含有量約60％） 85％
各試料の測定結果は第１表の通りであつた。
The present invention relates to an oil-soluble composition containing fat - soluble vitamins that is clear and has excellent stability over a long period of time. ) and a specified glycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, or a mixture of two or three thereof as an oil solubilizer. It is. Vitamin B2 butyrate, a fatty vitamin, has recently been shown to reduce lipid peroxide, blood HDL-C,
It is considered clinically useful for improving abnormal LDL values. Conventionally, vitamin B 2 butyrate has been prepared in powder form by adding it to tablets, granules, or powders, or by dispersing it in an aqueous and/or oily suspension. Also, 1% by weight of vitamin B 2 butyrate
Oil-soluble compositions formulated in small quantities up to 100 ml have been used in pharmaceuticals, foods, etc., but it has been difficult to produce clear and stable oil-soluble compositions formulated in large quantities. The present invention provides an oil-soluble composition containing fat-soluble vitamins that eliminates the above-mentioned drawbacks and can contain from 2% by weight to a maximum of 25% by weight of vitamin B 2 butyrate. 2
(a) Fatty acid ester as an oil-based solubilizer is added to the butyric acid ester as a monoester of a fatty acid having 6 to 12 carbon atoms, or a di- and/or combination of the monoester and the fatty acid ester.
or glycerin fatty acid ester which is triester, (b) fatty acid ester is a fatty acid with carbon number of 12 to
(c) Fatty acid ester is a monoester of a fatty acid having 12 to 18 carbon atoms, or a di- and/or tri-ester with the monoester, or a di- and/or tri-ester with the monoester. and/or triester, and the number of added moles of ethylene oxide is 2 to 2.
30, or (d) a mixture of two or three of the above (a), (b) and (c), and at that time vitamin B 2
The present invention is an oil-soluble composition containing a fat-soluble vitamin that remains clear for a long time and is characterized by a tetrabutyric acid ester compounding ratio of 2 to 25% by weight. According to the invention, 2% by weight of vitamin B 2 butyrate
A stable oil-soluble composition can be obtained that can be blended in large amounts up to 25% by weight, and can be stored stably for a long period of time without turbidity or precipitation of crystals. In the oil-soluble composition according to the present invention, the glycerin fatty acid ester used as an oil-based solubilizer to be added to the vitamin B 2 butyrate ester has a fatty acid having a carbon number of 4 or more.
18, preferably 6 to 12 fatty acid monoesters,
or the monoester and diester and/or triester, preferably 40% by weight of the monoester
The sorbitan fatty acid ester is a fatty acid ester containing 12 to 18 carbon atoms of a fatty acid, or a diester and/or triester of the monoester, preferably a fatty acid ester containing 40% by weight or more of a monoester. In the polyoxyethylene sorbitan fatty acid ester, the number of moles of added ethylene oxide is 2 to 30, preferably 20, and the number of carbon atoms in the fatty acid is 12 to 18, preferably
18 fatty acid monoesters, or diesters and/or triesters of the monoesters, preferably fatty acid esters containing 40% by weight or more of monoesters. The oil-soluble composition according to the present invention can be prepared by blending a specific glycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, or a mixture thereof, so that the blending ratio of vitamin B 2 butyric acid ester is mixed into the oil-soluble composition. is different from the conventional one (conventionally, the blending ratio was 1
(weight% or less), from 2% to a maximum of 25% by weight, and despite such a high blending ratio, it has achieved clear stability over a long period of time, something that could not previously be expected. It is something. Note that when the blending ratio of vitamin B 2 butyrate according to the present invention exceeds 25% by weight, it becomes difficult to prepare the intended oil-soluble composition, and when it exceeds 30% by weight, it becomes impossible to prepare. The oil-soluble composition containing vitamin B 2 butyrate according to the present invention may optionally contain fat-soluble vitamins such as vitamin A, vitamin E, and vitamin D, as well as rice oil, wheat germ oil, soybean oil, cottonseed oil, and rapeseed oil. ,
Vegetable oils such as rattan oil can also be mixed. The vitamin B 2 butyrate-containing oil-soluble composition of the present invention and the composition further mixed with fat-soluble vitamins or vegetable oil can be filled into soft capsules, hard capsules, or microcapsules. EXAMPLES The present invention will be described in detail with reference to Examples below, but the present invention is not limited to the Examples below. Example 1 An oil-soluble composition according to the present invention was obtained as follows. That is, the oil-soluble composition according to the present invention is prepared by blending 2, 10, and 25% by weight of vitamin B 2 butyrate and 98, 90, and 75% by weight of the oil-based solubilizers (A) to (G) shown below, respectively. The turbidity of these oils was measured using a Poitzk integrating sphere turbidity meter using each filtered and refined oil as a control, and the clarity was examined based on the results. (A) Sorbitan laurate ester (monoester content approximately 60%) 100% (B) Sorbitan oleate ester/POE (20)
(Monoester content: approx. 80%) 100% (C) Caprylic acid glycerin ester (monoester content: approx. 55%) 100% (D) Sorbitan oleate ester/POE (20)
(Monoester content approx. 80%) 10% Sorbitan oleate ester (Monoester content approx. 90%) 90% (E) Sorbitan stearate ester/POE
(20) (Monoester content approx. 40%) 10% Oleic acid glycerin ester (Monoester content approx. 40%) 90% (F) Caprylic acid glycerin ester (Monoester content approx. 95%) 92% Sorbitan laurate Ester (monoester content approx. 60%) 8% (G) Sorbitan laurate ester (monoester content approx. 60%) 8% Sorbitan oleate ester/POE (20)
(Monoester content: approximately 90%) 7% Caproic acid glycerin ester (monoester content: approximately 60%) 85% The measurement results for each sample were as shown in Table 1.
【表】【table】
【表】【table】
【表】
実施例 ２
本発明による他の油溶組成物を下記の如くにし
て得た。すなわちビタミンB2酪酸エステル２，
10及び25重量％、下記に示す(H)〜（Ｎ）の油性可
溶化剤それぞれ50，45及び45重量％並びに下記(H)
〜（Ｎ）の植物油及び脂溶性ビタミン類の合計そ
れぞれ48，45及び30重量％とを配合して本発明に
よる油溶組成物を得、実施例１と同様にして濁度
を測定して澄明度を検討した。
(H) オレイン酸ソルビタンエステル（モノエステ
ル含有量約90％） 60％
植物油 20％
脂溶性ビタミン 20％
(I) オレイン酸ソルビタンエステル・POE（20）
（モノエステル含有量約80％） 60％
植物油 20％
脂溶性ビタミン 20％
(J) カプリル酸グリセリンエステル（モノエステ
ル含有量約55％） 60％
植物油 20％
脂溶性ビタミン 20％
(K) オレイン酸ソルビタンエステル．POE（20）
（モノエステル含有量約80％） ７％
ラウリル酸ソルビタンエステル（モノエステル
含有量約60％） 53％
植物油 20％
脂溶性ビタミン 20％
(L) ステアリン酸ソルビタンエステル・POE
（20）（モノエステル含有量約40％） ７％
オレイン酸グリセリンエステル（モノエステル
含有量約40％） 53％
植物油 20％
脂溶性ビタミン 20％
(M) オレイン酸ソルビタンエステル（モノエス
テル含有量約90％） 10％
カプリル酸グリセリンエステル（モノエステル
含有量約55％） 50％
植物油 20％
脂溶性ビタミン 20％
(N) ステアリン酸ソルビタンエステル（モノエ
ステル含有量約50％） ８％
オレイン酸ソルビタンエステル・POE（20）
（モノエステル含有量約90％） ７％
カプリル酸グリセリンエステル（モノエステル
含有量約60％） 45％
植物油 20％
脂溶性ビタミン 20％
（なお、植物油としてはいずれもナタネ油、小
麦胚芽油など、脂溶性ビタミンとしてはビタミ
ンＡ、ビタミンＥなどを使用した）
各試料の測定結果は第２表の通りであつた。[Table] Example 2 Another oil-soluble composition according to the present invention was obtained as follows. That is, vitamin B 2 butyrate ester 2,
10 and 25% by weight, 50, 45 and 45% by weight of the oil-based solubilizers shown below (H) to (N), respectively, and the following (H)
An oil-soluble composition according to the present invention was obtained by blending vegetable oils and fat-soluble vitamins of ~(N) with a total of 48, 45, and 30% by weight, respectively, and the turbidity was measured in the same manner as in Example 1. We considered the degree. (H) Sorbitan oleate ester (monoester content approximately 90%) 60% Vegetable oil 20% Fat-soluble vitamins 20% (I) Sorbitan oleate ester/POE (20)
(Monoester content approx. 80%) 60% Vegetable oil 20% Fat-soluble vitamins 20% (J) Caprylic acid glycerin ester (Monoester content approx. 55%) 60% Vegetable oil 20% Fat-soluble vitamins 20% (K) Oleic acid Sorbitan ester. POE (20)
(Monoester content approx. 80%) 7% Lauric acid sorbitan ester (Monoester content approx. 60%) 53% Vegetable oil 20% Fat-soluble vitamins 20% (L) Stearic acid sorbitan ester/POE
(20) (Monoester content approx. 40%) 7% Oleic acid glycerin ester (Monoester content approx. 40%) 53% Vegetable oil 20% Fat-soluble vitamins 20% (M) Oleic acid sorbitan ester (Monoester content approx. 90%) 10% Caprylic acid glycerin ester (monoester content approx. 55%) 50% Vegetable oil 20% Fat-soluble vitamins 20% (N) Stearic acid sorbitan ester (monoester content approx. 50%) 8% Oleic acid sorbitan ester・POE (20)
(Monoester content: approx. 90%) 7% Caprylic acid glycerin ester (monoester content: approx. 60%) 45% Vegetable oil 20% Fat-soluble vitamins 20% (In addition, vegetable oils include rapeseed oil, wheat germ oil, etc.) The fat-soluble vitamins used were vitamin A, vitamin E, etc.) The measurement results for each sample were as shown in Table 2.
【表】【table】
【表】【table】
【表】
比較例 １
本発明による油溶組成物と対比するため下記従
来例（Ｏ）〜（Ｘ）の組成物を得た。すなわちビ
タミンB2酪酸エステル２及び10重量％と、植物
油単独、又は植物油と脂溶性ビタミン混合物をそ
れぞれ98及び90重量％を配合して油溶組成物を
得、これらを実施例１と同様にして濁度を測定
し、澄明度を検討した。
(O) ナタネ油 100％
(P) 小麦胚芽油 100％
(Q) ダイズ油 100％
(R) ナタネ油 60％
脂溶性ビタミン 40％
(S) ラツカセイ油 60％
脂溶性ビタミン 40％
(T) 小麦胚芽油 60％
脂溶性ビタミン 40％
（なお、脂溶性ビタミンとしてはビタミンＡ，
ビタミンＥなどを使用した。
各試料の測定結果は第３表の通りであつた。[Table] Comparative Example 1 In order to compare with the oil-soluble composition according to the present invention, the following compositions of conventional examples (O) to (X) were obtained. That is, an oil-soluble composition was obtained by blending 2 and 10% by weight of vitamin B 2 butyric acid ester and 98 and 90% by weight of vegetable oil alone or a mixture of vegetable oil and fat-soluble vitamins, respectively, and these were prepared in the same manner as in Example 1. Turbidity was measured and clarity was examined. (O) Rapeseed oil 100% (P) Wheat germ oil 100% (Q) Soybean oil 100% (R) Rapeseed oil 60% Fat-soluble vitamins 40% (S) Radix oil 60% Fat-soluble vitamins 40% (T) Wheat Germ oil 60% Fat-soluble vitamins 40% (Furthermore, fat-soluble vitamins include vitamin A,
I used vitamin E. The measurement results for each sample were as shown in Table 3.
【表】【table】
【表】
実施例１及び２並びに比較例１の結果すなわち
第１，２及び３表の結果は次の通りである。
(1) ビタミンB2酪酸エステル２重量％配合の場
合、その配合直後に於て、比較例すなわち第３
表（Ｏ）〜（Ｔ）の各試料の濁度に対し、本明
による組成粉(A)〜(G)及び(H)〜（Ｎ）の各試料の
濁度はきわめて低く、したがつて澄明性におい
てきわめてすぐれている。
また25℃、３ケ月及び25℃、３ケ年保存に於
て本発明に於ける各組成物はその澄明度に於て
ほとんど差異をみとめないが、比較例に於ては
その保存期間に応じて大きく澄明度が低下して
いる。
(2) ビタミンB2酪酸エステル10重量％配合の場
合、その配合直後に於て及び時間経過後に於
て、(A)〜(G)及び(H)〜（Ｎ）のいずれもビタミン
B2酪酸エステル２重量％の澄明度とほとんど
差異をみとめないが、比較例（Ｏ）〜（Ｔ）に
於てはその濁度がビタミンB2酪酸エステル２
重量％の場合に比して大幅に増大し、したがつ
て澄明度はきわめて低下している。
(3) ビタミンB2酪酸エステル25重量％配合の場
合、その配合直後並びに時間経過後に於ても(A)
〜(G)及び(H)〜（Ｎ）のいずれも澄明度に於て
は、ビタミンB2酪酸エステル10重量％配合の
場合に比し、やや劣る傾向にあるが、ビタミン
B2酪酸エステル２重量％配合の比較例の場合
と比較すれば、その澄明度はきわめてすぐれて
いる。
比較例の場合はもはや全く測定不能であつ
た。
以上詳述した如く、本発明による脂溶性ビタミ
ン配合油溶組成物は実施例に詳細に示す如く、２
重量％から最高25重量％配合に於てもその澄明度
にすぐれ、しかも長期にわたつてその澄明度はほ
とんど低下せず、きわめて安定したものである。[Table] The results of Examples 1 and 2 and Comparative Example 1, that is, the results of Tables 1, 2, and 3 are as follows. (1) In the case of 2% by weight of vitamin B 2 butyrate ester, the comparative example, that is, the third
Compared to the turbidity of each sample in Tables (O) to (T), the turbidity of each sample of composition powders (A) to (G) and (H) to (N) according to the present invention is extremely low. It has excellent clarity. Furthermore, when stored at 25°C for 3 months and at 25°C for 3 years, there is almost no difference in clarity between the compositions of the present invention; The clarity has decreased significantly. (2) In the case of 10% by weight of vitamin B 2 butyrate ester, both (A) to (G) and (H) to (N) were found to contain vitamins immediately after the combination and after a period of time.
There is almost no difference in clarity from the clarity of 2% by weight of B 2 butyrate ester, but in Comparative Examples (O) to (T), the turbidity is lower than that of vitamin B 2 butyrate 2.
% by weight, and the clarity is therefore extremely low. (3) In the case of 25% by weight of vitamin B 2 butyrate ester, (A) immediately after the combination and after time has elapsed.
The clarity of both ~(G) and (H) ~(N) tends to be slightly inferior to that of the case containing 10% by weight of vitamin B 2 butyrate;
When compared with the comparative example containing 2% by weight of B 2 butyric acid ester, the clarity is extremely excellent. In the case of the comparative example, it was no longer possible to measure it at all. As detailed above, the oil-soluble composition containing fat-soluble vitamins according to the present invention has two
It has excellent clarity even when the content is from 25% by weight up to 25% by weight, and the clarity hardly decreases over a long period of time, making it extremely stable.
Claims (1)
溶化剤として (a) 脂肪酸エステルが、脂肪酸の炭素数６乃至12
の脂肪酸のモノエステル、あるいは該モノエス
テルとジ及び／又はトリエステルであるグリセ
リン脂肪酸エステル、 (b) 脂肪酸エステルが、脂肪酸の炭素数12乃至18
の脂肪酸のモノエステル、あるいは該モノエス
テルとジ及び／又はトリエステルであるソルビ
タン脂肪酸エステル、 (c) 脂肪酸エステルが、脂肪酸の炭素数12乃至18
の脂肪酸のモノエステル、あるいは該モノエス
テルとジ及び／又はトリエステルであり、且つ
酸化エチレンの付加モル数が２乃至30であるポ
リオキシエチレンソルビタン脂肪酸エステル、
あるいは (d) 上記(a)，(b)及び(c)の２種又は３種の混合物を
配合し、且つその際ビタミンB2テトラ酪酸エ
ステルの配合率が２〜25重量％であることを特
徴とする長期にわたり澄明な脂溶性ビタミン配
合油溶組成物。 ２ 特許請求の範囲第１記載の組成物に於いて、
ポリオキシエチレンソルビタン脂肪酸エステルの
酸化エチレンの付加モル数が20、脂肪酸の炭素数
18の脂肪酸エステルであることを特徴とする組成
物。[Scope of Claims] 1. Vitamin B 2 tetrabutyric acid ester, as an oil solubilizer (a) fatty acid ester containing fatty acid having 6 to 12 carbon atoms;
(b) Glycerin fatty acid ester which is a monoester of a fatty acid, or a di- and/or triester with the monoester;
(c) sorbitan fatty acid ester which is a monoester of a fatty acid, or a di- and/or tri-ester with the monoester;
A polyoxyethylene sorbitan fatty acid ester which is a monoester of a fatty acid, or a di- and/or triester with the monoester, and has an added mole number of ethylene oxide of 2 to 30,
Or (d) A mixture of two or three of the above (a), (b) and (c) is blended, and at that time, it is confirmed that the blending ratio of vitamin B 2 tetrabutyrate is 2 to 25% by weight. An oil-soluble composition containing fat-soluble vitamins that remains clear for a long time. 2. In the composition according to claim 1,
The number of moles of ethylene oxide added to polyoxyethylene sorbitan fatty acid ester is 20, and the number of carbon atoms in the fatty acid is
A composition characterized in that it is a fatty acid ester of 18.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57091466A JPS58208215A (en) | 1982-05-31 | 1982-05-31 | Oil-soluble composition containing fat-soluble vitamin |
| GB08307543A GB2120935B (en) | 1982-05-31 | 1983-03-18 | Fat-soluble vitamin preparation |
| SE8301565A SE461892B (en) | 1982-05-31 | 1983-03-22 | OIL-SOLUBLE COMPOSITION OF VITAMIN B BUTYRATE |
| DE3311008A DE3311008C2 (en) | 1982-05-31 | 1983-03-25 | Oil-soluble preparation containing a fat-soluble vitamin |
| CH1664/83A CH656531A5 (en) | 1982-05-31 | 1983-03-25 | PREPARATION OF FAT-SOLUBLE VITAMIN IN OEL. |
| FR8305239A FR2527440B1 (en) | 1982-05-31 | 1983-03-30 | OLEOSOLUBLE COMPOSITION CONTAINING A VITAMIN SOLUBLE IN FATS |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57091466A JPS58208215A (en) | 1982-05-31 | 1982-05-31 | Oil-soluble composition containing fat-soluble vitamin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58208215A JPS58208215A (en) | 1983-12-03 |
| JPH044299B2 true JPH044299B2 (en) | 1992-01-27 |
Family
ID=14027151
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57091466A Granted JPS58208215A (en) | 1982-05-31 | 1982-05-31 | Oil-soluble composition containing fat-soluble vitamin |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS58208215A (en) |
| CH (1) | CH656531A5 (en) |
| DE (1) | DE3311008C2 (en) |
| FR (1) | FR2527440B1 (en) |
| GB (1) | GB2120935B (en) |
| SE (1) | SE461892B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5639724A (en) * | 1984-07-24 | 1997-06-17 | Sandoz Ltd. | Cyclosporin galenic forms |
| JPS63130535A (en) * | 1986-11-19 | 1988-06-02 | Nisshin Kagaku Kk | Antihistamine agent for oral administration |
| US7081445B2 (en) | 1989-02-20 | 2006-07-25 | Novartis Ag | Cyclosporin galenic forms |
| GB9325445D0 (en) | 1993-12-13 | 1994-02-16 | Cortecs Ltd | Pharmaceutical formulations |
| SG115386A1 (en) | 1997-01-30 | 2005-10-28 | Novartis Ag | Hard gelatine capsules containing pharmaceutical compositions substantially free of any oil |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR8014M (en) * | 1968-01-09 | 1970-07-27 | ||
| US3962436A (en) * | 1969-06-03 | 1976-06-08 | Sumitomo Chemical Company, Limited | Pharmaceutical compositions having controlled rate of gastro-intestinal absorption |
| NL7012460A (en) * | 1970-08-22 | 1972-02-24 | ||
| US3932634A (en) * | 1973-06-28 | 1976-01-13 | Pfizer Inc. | High potency vitamin water dispersible formulations |
-
1982
- 1982-05-31 JP JP57091466A patent/JPS58208215A/en active Granted
-
1983
- 1983-03-18 GB GB08307543A patent/GB2120935B/en not_active Expired
- 1983-03-22 SE SE8301565A patent/SE461892B/en not_active IP Right Cessation
- 1983-03-25 DE DE3311008A patent/DE3311008C2/en not_active Expired
- 1983-03-25 CH CH1664/83A patent/CH656531A5/en not_active IP Right Cessation
- 1983-03-30 FR FR8305239A patent/FR2527440B1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR2527440B1 (en) | 1987-05-15 |
| CH656531A5 (en) | 1986-07-15 |
| GB8307543D0 (en) | 1983-04-27 |
| GB2120935A (en) | 1983-12-14 |
| FR2527440A1 (en) | 1983-12-02 |
| DE3311008A1 (en) | 1983-12-01 |
| GB2120935B (en) | 1985-10-23 |
| SE8301565L (en) | 1983-12-01 |
| SE8301565D0 (en) | 1983-03-22 |
| DE3311008C2 (en) | 1986-04-10 |
| JPS58208215A (en) | 1983-12-03 |
| SE461892B (en) | 1990-04-09 |
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