JPH01238526A - Vitamin e absorption-improving preparation - Google Patents

Vitamin e absorption-improving preparation

Info

Publication number
JPH01238526A
JPH01238526A JP63062904A JP6290488A JPH01238526A JP H01238526 A JPH01238526 A JP H01238526A JP 63062904 A JP63062904 A JP 63062904A JP 6290488 A JP6290488 A JP 6290488A JP H01238526 A JPH01238526 A JP H01238526A
Authority
JP
Japan
Prior art keywords
vitamin
absorption
polyoxyethylene sorbitan
preparation
sorbitan monostearate
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.)
Granted
Application number
JP63062904A
Other languages
Japanese (ja)
Other versions
JP2676770B2 (en
Inventor
Yasuo Ozawa
小沢 康雄
Kenji Yamada
憲司 山田
Masayuki Akimoto
秋元 雅之
Yoshitaka Tanaka
善孝 田中
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Taisho Pharmaceutical Co Ltd
Original Assignee
Taisho Pharmaceutical Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Taisho Pharmaceutical Co Ltd filed Critical Taisho Pharmaceutical Co Ltd
Priority to JP63062904A priority Critical patent/JP2676770B2/en
Publication of JPH01238526A publication Critical patent/JPH01238526A/en
Application granted granted Critical
Publication of JP2676770B2 publication Critical patent/JP2676770B2/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Abstract

PURPOSE:To provide a preparation having an enhanced vitamin E-dissolving property, a high vitamin E-absorbing property from digestive tracts and an improved bio-availability, by compounding the vitamin E with polyoxyethylene sorbitan monostearate in a specific ratio. CONSTITUTION:1pt.wt. of vitamin E is compounded with 0.01-10pts.wt., preferably 1-10pts.wt., of polyoxyethylene sorbitan monostearate. The preparation may be further compounded with fats and oils such as fatty acids or vegetable oils, alcohols such as ethanol or glycerol, surfactants such as sorbitan compounds, other additives for the preparation in an amount of 0.5-50wt.%.

Description

【発明の詳細な説明】 [産業上の利用分野] 本発明はビタミンEの経口吸収改善製剤に関する。[Detailed description of the invention] [Industrial application field] The present invention relates to a preparation for improving oral absorption of vitamin E.

[従来の技術] ビタミンEは、血液循環障害、毛細血管内の血流停滞を
改善するだけでなく、感染症や癌、更には虚血性心疾患
の出現率を減少させるのに重要な働き゛をしていると言
われている。
[Prior Art] Vitamin E not only improves blood circulation disorders and stagnation of blood flow in capillaries, but also plays an important role in reducing the incidence of infectious diseases, cancer, and even ischemic heart disease. It is said that he is doing

しかしながら、毎日摂取される食事の内容を変更するこ
とによって血漿中のビタミンE濃度を上昇させることは
容易ではない。
However, it is not easy to increase the vitamin E concentration in plasma by changing the contents of daily meals.

その上、−膜内にビタミンEの消化管からの吸収には限
界があると認められるために臨床用量での吸収性に問題
があるとされている。例えば小動物(ラット)での吸収
率はわずかに10〜42%と見積もられるし、マックリ
ンが最近報告したヒトの結果[インファケム、第7巻、
第3号、第24ページ(1986年)コでもdl−酢酸
トフフェロール8001、U、28日間連日経口投与し
た時、血漿中濃度が之倍程度となるに過ぎない。
Furthermore, it is recognized that there is a limit to the absorption of vitamin E from the gastrointestinal tract within the membrane, which poses a problem in absorption at clinical doses. For example, the absorption rate in small animals (rats) is estimated to be only 10-42%, and Macklin recently reported human results [Infachem, Vol. 7,
No. 3, page 24 (1986), when dl-topherol acetate 8001, U, was orally administered for 28 consecutive days, the plasma concentration was only about twice that.

この為、ビタミンEの消化管吸収を改善するために種々
の試みがなされてきた。その1つとして、ポリオキシエ
チレンソルビクンモノオレートなどのポリオキシエチレ
ンソルビタン詣肪酸エステル類添加による可溶化効果を
期待する方法がある。すなわち、ケラ−(Kall−e
r )らはラットに落花生油あるいはポリ才キシエチレ
ンソルビクンモノオレートの投与形態で60〜76%の
吸収率を報告している〔インターナショナル・ジャーナ
ル・才ブ・ビタミノロジー・アンド・二二一トリッショ
ナル・リサーチ、第42巻、第394ページ(1972
年〕]。また、ベイトマン(Bateman )らはポ
リオキシエチレンソルビタンモノオレート、エタノール
及びプロピレングリコールより成る基剤を使って、d−
α−トフフエロールをヒトに投与したところ、市販の錠
剤や油製剤よりも吸収が向上する゛ことを報告している
For this reason, various attempts have been made to improve the gastrointestinal absorption of vitamin E. One such method is to expect a solubilizing effect by adding polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbicun monooleate. That is, Kall-e
reported an absorption rate of 60% to 76% in rats using peanut oil or polyoxyethylene sorbicun monooleate [International Journal of Vitaminology and 221 Tri. National Research, Volume 42, Page 394 (1972
Year〕]. Also, Bateman et al. used a base consisting of polyoxyethylene sorbitan monooleate, ethanol, and propylene glycol to
When α-tofuferol was administered to humans, it was reported that absorption was improved compared to commercially available tablets and oil preparations.

[発明が解決しようとする課題] 一般に、ポリオキシエチレンソルビタン脂肪酸エステル
類などの非イオン性界面活性剤の添加はビタミンEの消
化管吸収をある程度改善するが、高投与量での吸収の不
完全性などを考慮に入れると、更番こ吸収の優れた製剤
の開発が望まれている。
[Problem to be solved by the invention] Generally, the addition of nonionic surfactants such as polyoxyethylene sorbitan fatty acid esters improves the gastrointestinal absorption of vitamin E to some extent, but absorption is incomplete at high doses. Taking into consideration the characteristics, it is desired to develop a formulation with excellent absorption of serobanco.

〔課題を解決するだめの手段] このような実情に鑑み、本発明者らはビタミンEの消化
管からの吸収性に対する基剤の効果を種々検討した結果
、意外にもポリオキシエチレンソルビタンモノステアレ
ートがポリオキシエチレンソルビタンモノオレートや他
のポリオキシエチレンソルビタン脂肪酸エステル類を配
合した時よりも、消化管からのビタミンEの吸収が増大
することを見い出し、本発明を完成するに至った。
[Means to Solve the Problem] In view of the above circumstances, the present inventors investigated various effects of bases on the absorption of vitamin E from the gastrointestinal tract, and found that polyoxyethylene sorbitan monostearer The present inventors have discovered that absorption of vitamin E from the digestive tract is increased compared to when polyoxyethylene sorbitan monooleate or other polyoxyethylene sorbitan fatty acid esters are blended, leading to the completion of the present invention.

すなわち、本発明は1重量部のビタミンEに対し0.0
1〜10重量部のポリオキシエチレンソルビタンモノス
テアレートを配合することを特徴とするビタミンEの経
口吸収改善製剤である。
That is, the present invention provides 0.0 parts by weight of vitamin E.
This is a preparation for improving the oral absorption of vitamin E, which is characterized by containing 1 to 10 parts by weight of polyoxyethylene sorbitan monostearate.

本発明は、ビタミンEを含有する経口製剤に適した剤層
中に特定量のポリオキシエチレンソルビタンモノステア
レートを配合することによって実施することができる。
The present invention can be carried out by incorporating a specific amount of polyoxyethylene sorbitan monostearate into a drug layer suitable for oral formulations containing vitamin E.

この1重量部のビタミンEに対してのポリオキシエチレ
ンソルビタンモノステアレートの配合量は、0.01〜
10重量部であり、好ましくは1重量部〜10重量部の
ポリオキシエチレンソルビタンモノまた、本発明におい
て、ビタミンEとは、トフフェロール、酢酸トコフェロ
ール、フハク酸トコフェロール、フハク酸トフフエロー
ルカルシウム及びその他のエステル類を言う。
The blending amount of polyoxyethylene sorbitan monostearate for 1 part by weight of vitamin E is 0.01 to
10 parts by weight, preferably 1 to 10 parts by weight of polyoxyethylene sorbitan mono. Also, in the present invention, vitamin E refers to tofuferol, tocopherol acetate, tocopherol succinate, tofuferol calcium succinate and other Refers to esters.

また、上記製剤には脂肪酸及び植物油などの油詣類する
いはプロピレングリコール、エタノール又はグリセリン
などのアルコール類、ソルビタン類などの界面活性剤、
その他の製剤添加物を第3成分として添加しても良い。
In addition, the above formulations may contain oils such as fatty acids and vegetable oils, alcohols such as propylene glycol, ethanol or glycerin, and surfactants such as sorbitans.
Other formulation additives may be added as a third component.

この場合、配合割合は特に限定しないが通常、製剤に対
し0.5〜50重量%であることが望ましい。
In this case, the blending ratio is not particularly limited, but it is usually desirable to be 0.5 to 50% by weight based on the formulation.

[発明の効果] 本発明により、ビタミンEの可溶性能及び消化管からの
吸収性が高まり、バイオアベイラビリティ−が向上した
[Effects of the Invention] According to the present invention, the solubility and absorbability of vitamin E from the gastrointestinal tract were increased, and the bioavailability was improved.

[、実1例コ 以下、実施例および試験例を挙げて本発明を具体的に説
明する。
[Example 1] Hereinafter, the present invention will be specifically explained with reference to Examples and Test Examples.

東JL例」2 酢酸トコフェロール1gをポリオキシエチレンソルビタ
ンモノステアレート2gと共に加温溶解し、2号の硬カ
プセル15個に充填した。
East JL Example 2 1 g of tocopherol acetate was dissolved by heating with 2 g of polyoxyethylene sorbitan monostearate, and the mixture was filled into 15 No. 2 hard capsules.

夫1■ユ 酢酸トコフェロール1gをポリオキシエチレンソルビタ
ンモノステアレート2gと共に加温溶解後、大豆油1g
を加え、攪拌後常法により、2号の硬カプセル15個に
充填した。
Husband 1: Dissolve 1g of tocopherol euacetate with 2g of polyoxyethylene sorbitan monostearate by heating, then add 1g of soybean oil.
was added, stirred, and then filled into 15 No. 2 hard capsules by a conventional method.

夫五勇ユ α−トコフェロール1gをポリオキシエチレンソルビタ
ンモノステアレート2gと加温混和後、グリセリン0.
5g及びプロピレングリコール0.5gをpえ、攪拌後
、常法により、31号の硬カプセル15個に充填した。
After heating and mixing 1 g of Fugoyu α-tocopherol with 2 g of polyoxyethylene sorbitan monostearate, 0.0 g of glycerin was added.
5 g and propylene glycol 0.5 g, stirred, and filled into 15 No. 31 hard capsules by a conventional method.

実JE医〕ヨ フハク酸トフフェロール10gをボリ才キシエチレンツ
ルビクンモノステアレート10gと共に加温溶解し、こ
の溶液をヒドロキシプロピルセルロース25g、結晶セ
ルロース30g及び乳糖30gの混合物に均一に分散さ
せた。
Practical JE Doctor] 10 g of topherol iosuccinate was dissolved by heating together with 10 g of polyoxyethylene turvikun monostearate, and this solution was uniformly dispersed in a mixture of 25 g of hydroxypropyl cellulose, 30 g of crystalline cellulose, and 30 g of lactose.

次いで、この分散物を乾燥整粒後、ステアリン酸マグネ
シウム1gを加えて混合し、1錠100mgの錠剤10
00個を圧縮成形した。
Next, after drying and sizing this dispersion, 1 g of magnesium stearate was added and mixed to form 100 mg tablets.
00 pieces were compression molded.

実施例5 酢酸トコフェロール1gをポリオキシエチレンソルビク
ンモノステアレート0.5gと加温溶解後、パナセート
8102.5gを加え、攪拌後、常法により2号の軟カ
プセル15個に充填した。
Example 5 After heating and dissolving 1 g of tocopherol acetate with 0.5 g of polyoxyethylene sorbicun monostearate, 8102.5 g of panasate was added, and after stirring, the mixture was filled into 15 No. 2 soft capsules by a conventional method.

試験例1(バイオアベイラビリティ−試験)(検体) 検体1;実施例1の硬カプセル剤 検体2;酢酸トコフェノール100ntとポリオキシエ
チレンソルビタンモノオレート200■を1カプセル中
に含む硬カプセル剤 検体3;酢酸トコフェロールの原体のみ100■を含有
する硬カプセル剤 検体4;酢酸トコフェロール100TrV、とポリオキ
シエチレンソルビタンモノオレート160■、プロピレ
ングリフール20■及びエタノール20■を含有する硬
カプセル剤 (試験動物) 試験実施前日より絶食きせたピーグル大(体重10〜1
3kg)を1群3頭用いた。
Test Example 1 (Bioavailability Test) (Sample) Sample 1; Hard capsule sample 2 of Example 1; Hard capsule sample 3 containing 100 nt of tocopherol acetate and 200 ml of polyoxyethylene sorbitan monooleate in one capsule; Hard capsule containing 100 µV of tocopherol acetate only; Hard capsule containing 100 TrV of tocopherol acetate, 160 µ of polyoxyethylene sorbitan monooleate, 20 µ of propylene glyfur, and 20 µ of ethanol (test animal) Peagle-sized (weight 10-1
3 kg) were used in each group.

(投与方法) 各検体をそれぞれ別個の群のピーグル犬に経口投与し、
直後に水30m1を強制的に投与した。
(Administration method) Each sample was orally administered to a separate group of peagle dogs,
Immediately thereafter, 30 ml of water was forcibly administered.

(血液試料の採取と処理) ゛投与直前、投与後2時間、4時間、6時間、8時間及
び24時間目に前足静脈血液3mQを採取して遠心分離
後の血漿を試料とした。
(Collection and processing of blood samples) Immediately before administration, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours after administration, 3 mQ of foreleg vein blood was collected, and the plasma after centrifugation was used as a sample.

(定量法) 各血漿中の総α−トコフェロール濃度は高速クロマトグ
ラフィーにより測定した。
(Quantitative method) The total α-tocopherol concentration in each plasma was measured by high performance chromatography.

すなわち、試料0.5mlに蒸留水0.5mlを加え希
釈し、エタノール0゜5mlで除タンパクした後にヘキ
サン5mlを加え抽出した。10分間振盪し、遠心分離
した後ヘキサン層4mlを採取した。
That is, 0.5 ml of a sample was diluted by adding 0.5 ml of distilled water, protein was removed with 0.5 ml of ethanol, and then 5 ml of hexane was added for extraction. After shaking for 10 minutes and centrifuging, 4 ml of hexane layer was collected.

ヘキサン層を蒸発乾固し残渣にエタノールを加え、これ
を高速液体クロマトグラフに注入した。
The hexane layer was evaporated to dryness, ethanol was added to the residue, and this was injected into a high performance liquid chromatograph.

カラムは長さ15(lln、直径4mmのものを用い、
充填剤としてTSK−Gel LS−410(東洋曹達
)を用いた。溶離液はメタノール:水の混液(94:6
)を用い、検出は291nmの紫外部吸収波長を使用し
た。
The column used was one with a length of 15 (lln) and a diameter of 4 mm.
TSK-Gel LS-410 (Toyo Soda) was used as a filler. The eluent was a mixture of methanol and water (94:6).
), and the ultraviolet absorption wavelength of 291 nm was used for detection.

(結果) 投与直前の血漿濃度を差し引いた各採血時点の第1表 本発明により得られた検体1は対照として用いた検体2
,3.4よりも高い血中濃度を示した。
(Results) Table 1 for each blood collection time point after subtracting the plasma concentration immediately before administration Sample 1 obtained according to the present invention is Sample 2 used as a control
, 3.4.

Claims (1)

【特許請求の範囲】[Claims] 1)1重量部のビタミンEに対し0.01重量部〜10
重量部のポリオキシエチレンソルビタンモノステアレー
トを配合することを特徴とするビタミンEの経口吸収改
善製剤。
1) 0.01 parts by weight to 10 parts by weight per 1 part by weight of vitamin E
A preparation for improving oral absorption of vitamin E, which contains part by weight of polyoxyethylene sorbitan monostearate.
JP63062904A 1988-03-16 1988-03-16 Vitamin E absorption improving preparation Expired - Fee Related JP2676770B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP63062904A JP2676770B2 (en) 1988-03-16 1988-03-16 Vitamin E absorption improving preparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP63062904A JP2676770B2 (en) 1988-03-16 1988-03-16 Vitamin E absorption improving preparation

Publications (2)

Publication Number Publication Date
JPH01238526A true JPH01238526A (en) 1989-09-22
JP2676770B2 JP2676770B2 (en) 1997-11-17

Family

ID=13213706

Family Applications (1)

Application Number Title Priority Date Filing Date
JP63062904A Expired - Fee Related JP2676770B2 (en) 1988-03-16 1988-03-16 Vitamin E absorption improving preparation

Country Status (1)

Country Link
JP (1) JP2676770B2 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0532547A (en) * 1991-07-26 1993-02-09 Ss Pharmaceut Co Ltd Vitamin e pharmaceutical composition
JP2002020268A (en) * 2000-07-10 2002-01-23 Takeda Chem Ind Ltd Internal liquid containing fat-soluble substance
FR2861261A1 (en) * 2003-10-22 2005-04-29 Adisseo France Sas The use in animal nutrition of alimentary emulsifiers, especially sorbitol monolaurate and monooleate in association with a derivative of vitamin E, especially tocopherol acetate to improve its bioavailability
EP1696902A4 (en) * 2003-12-23 2007-03-07 Cognis Ip Man Gmbh Compositions containing d-tocopherol compound polybasic acid partial esters

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6034907A (en) * 1983-05-02 1985-02-22 アール・ピー・シエラー・コーポレイシヨン Vitamin or mineral composition for forming solid unit administration form

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6034907A (en) * 1983-05-02 1985-02-22 アール・ピー・シエラー・コーポレイシヨン Vitamin or mineral composition for forming solid unit administration form
JPS60105633A (en) * 1983-05-02 1985-06-11 ア−ル・ピ−・シエアラ−・プロプライアタリ−・リミテツド Vitamin composition

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0532547A (en) * 1991-07-26 1993-02-09 Ss Pharmaceut Co Ltd Vitamin e pharmaceutical composition
JP2002020268A (en) * 2000-07-10 2002-01-23 Takeda Chem Ind Ltd Internal liquid containing fat-soluble substance
FR2861261A1 (en) * 2003-10-22 2005-04-29 Adisseo France Sas The use in animal nutrition of alimentary emulsifiers, especially sorbitol monolaurate and monooleate in association with a derivative of vitamin E, especially tocopherol acetate to improve its bioavailability
EP1696902A4 (en) * 2003-12-23 2007-03-07 Cognis Ip Man Gmbh Compositions containing d-tocopherol compound polybasic acid partial esters

Also Published As

Publication number Publication date
JP2676770B2 (en) 1997-11-17

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