JPS58206540A - Beta-cyclodextrin inclusion compound of ubidecarenone and its preparation - Google Patents
Beta-cyclodextrin inclusion compound of ubidecarenone and its preparationInfo
- Publication number
- JPS58206540A JPS58206540A JP57089548A JP8954882A JPS58206540A JP S58206540 A JPS58206540 A JP S58206540A JP 57089548 A JP57089548 A JP 57089548A JP 8954882 A JP8954882 A JP 8954882A JP S58206540 A JPS58206540 A JP S58206540A
- Authority
- JP
- Japan
- Prior art keywords
- ubidecarenone
- cyclodextrin
- approximately
- endothermic peak
- beta
- 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
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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
Abstract
Description
【発明の詳細な説明】
この発明はユビデカレノンのβ−シクロデキス） ＩＪ
ン包接化合物およびその製造法に関するものである。[Detailed Description of the Invention] This invention relates to β-cyclodextrin of ubidecarenone (IJ)
The present invention relates to clathrate compounds and their production methods.
ユビデカレノンは、次の化学構造式を有する化合物であ
り、冠機能の改善に有効な医薬として広く使用されてい
る。Ubidecarenone is a compound having the following chemical structural formula, and is widely used as a drug effective for improving coronary function.
ユビデカレノンは水に極めて溶は難いため、これを経口
投与した。ときに吸収され難く、しかも低融点（４８〜
５０℃）であるため製剤の熱安定性に劣るという問題が
あった。Since ubidecarenone is extremely difficult to dissolve in water, it was administered orally. Sometimes it is difficult to absorb and has a low melting point (48~
50°C), there was a problem that the thermal stability of the formulation was poor.
このような間頌を解決するため、特開昭５５−１４７２
１９号、同５６−１２３０９号、同５６−１３１３９３
号、同５６−１４５２１４号、同５６−１４７２１９号
、同５６−１８９１４号公報に記載のような種々の製剤
化方法が試みられてきたが、未だ満足に実用化されるに
は到っていない。In order to resolve this interlude, Japanese Patent Application Laid-Open No. 55-1472
No. 19, No. 56-12309, No. 56-131393
Various formulation methods have been attempted, such as those described in Japanese Patent No. 56-145214, No. 56-147219, and No. 56-18914, but they have not yet been put into practical use satisfactorily. .
このような製剤化方法とは別にユビデカレノンを包接化
合物とし、こねによって上記のような問題を解決しよう
とする方法も試みらねている（特開昭５６−１０９５９
０号）。Apart from this formulation method, attempts have also been made to use ubidecarenone as a clathrate compound and knead it to solve the above-mentioned problems (Japanese Patent Laid-Open No. 10959/1989).
No. 0).
この方法は、補酵素Ｑ１．。（ユビデカレノン）１モル
対しβ−またはα−デキストリン１モルを包接させるも
のであるが、実施例に記載の方法により得られる目的物
は粉末Ｘ線回折スペクトルにおいて１９°および２３°
付近にユビデカレノンに由来するピークを示し、しかも
示差熱分析で５０℃付近に鋭い吸熱ピークを示すなど、
包接化が充分ではない。したがってユビデカレノンに起
因する上記のような問題が満足し
［得る程度には解決されていない。This method uses coenzyme Q1. . (Ubidecarenone) 1 mol to 1 mol of β- or α-dextrin is included, and the target product obtained by the method described in the example shows 19° and 23° in the powder X-ray diffraction spectrum.
It shows a peak derived from ubidecarenone nearby, and also shows a sharp endothermic peak around 50°C in differential thermal analysis.
Not enough inclusion. Therefore, the above problems caused by ubidecarenone are satisfied.
[It is not resolved to the extent that it can be obtained.
この発明の発明者はユビデカレノンとβ−シクロデキス
トリンとの完全なる包接化合物を得べく鉋、を研究の結
果、ユビデカレノン１モルに対してβ−シクロデキスト
リンを６モル以上作用させると、粉末Ｘ線回折ヌベク）
／しおよび示ことを見出し、この発明を完成した。The inventor of this invention tried to obtain a complete clathrate compound of ubidecarenone and β-cyclodextrin, and as a result of his research, he found that when 6 moles or more of β-cyclodextrin acts on 1 mole of ubidecarenone, powder X-ray Diffraction Nubek)
The inventors have discovered the following and completed this invention.
この発明の方法は、ユビデカレノン１モルに対してβ−
シクロデキストリンを３モル以上作用させることにより
行われる。In the method of this invention, β-
This is carried out by allowing 3 or more moles of cyclodextrin to act.
この方法は両者を適当な溶媒中で混合するだけでもよい
が、好ましくは前者を加熱融解したものと、後者の水溶
液とを加温ないし加熱下に混合するのがよい。生成する
包接化合物は常法により単離精製される。例えば両者の
反応を上記のように水溶液中で行うと、生成する包接化
合物が水に極めて溶は難いため反応液中に析出し、これ
を速、し分離などの常用の手段で分離することができる
。また、分離された生成物は、このようにして得られる
包接化合物を液体クロマトグラフ法で測定した給与１、
ユビデカレノンとβ−シクロデキストリンとの組成比は
約１：６であった。そして、その融点は約３００ｔ’。In this method, the two may be simply mixed in a suitable solvent, but it is preferable to heat and melt the former and mix the latter with an aqueous solution while heating or under heating. The resulting clathrate compound is isolated and purified by conventional methods. For example, when the reaction of both is carried out in an aqueous solution as described above, the clathrate compound formed is extremely difficult to dissolve in water, so it precipitates in the reaction solution and can be separated by a conventional means such as rapid separation. I can do it. In addition, the separated product was determined by measuring the clathrate compound obtained in this way using a liquid chromatography method.
The composition ratio of ubidecarenone and β-cyclodextrin was approximately 1:6. Its melting point is approximately 300t'.
であり、ユビデカレノンの低融点に起因する製ノンと同
様に水に楔めて溶は難いにもかかわらず、これをピーグ
ル大に経口投与したところ、る。Although it is difficult to dissolve in water due to the low melting point of ubidecarenone, similar to non-produced non-alcoholic acid, it was found that ubidecarenone was orally administered to peagle-sized animals.
実施例１
ユビデカレノン（４，３１）を８０℃に加熱して融解す
る。他方、β−シクロデキストリン（２９Ｆ）を蒸留水
（５００ｇ＋／）に加え、８０℃に加温して溶解する。Example 1 Ubidecarenone (4,31) is melted by heating to 80°C. On the other hand, β-cyclodextrin (29F) is added to distilled water (500g+/) and heated to 80°C to dissolve.
この水溶液に融解したユビデカレノンを加え、８０℃で
１０時間撹拌する。反応液中の生成物を遠心分離（！１
０００ｒｐｍ ＋ １０分間）し、得られるベレット状
の共沈物を８０℃に加温した蒸留水（５００ｇ／）に懸
濁し、遠心分離する操作を６回くり返したのチ、凍結乾
燥すると、ユビデカレノンのβ−シクロデキストリン包
接化合物（組成比的１：５）を得る。融点約３００℃（
分解）。Melted ubidecarenone was added to this aqueous solution and stirred at 80°C for 10 hours. Centrifuge the product in the reaction solution (!1
000 rpm + 10 minutes), the resulting pellet-like coprecipitate was suspended in distilled water (500 g/) heated to 80°C, and centrifugation was repeated 6 times. A β-cyclodextrin clathrate compound (composition ratio 1:5) is obtained. Melting point approximately 300℃ (
Disassembly).
水晶の粉末Ｘ線回折ヌベクトルを第１図に、示差熱分析
の結果を第２図にそれぞれ示す。Powder X-ray diffraction nuvector of the crystal is shown in FIG. 1, and results of differential thermal analysis are shown in FIG. 2, respectively.
第１図は、この発明の実施例１で得られた包接化合物の
粉末Ｘ線回折ヌベクトルであり、第２図はその示差熱分
析の結果を示すチャートであるＣFigure 1 is a powder X-ray diffraction nuvector of the clathrate compound obtained in Example 1 of the present invention, and Figure 2 is a chart showing the results of its differential thermal analysis.
Claims (1)
トリン３モル以上を作用させて得られる、次の物性を有
するユビデカレノンのβ−シクロデキストリン包接化合
物。 （１） 粉末Ｘ線回折スペクトルにおいて、ユビデカ
レノンに由来する１９° および２６°付近のピークを
示さず、７°付近、１２°付近および１８° 付近にピ
ークを示す。 （ト）示差熱分析において、ユビデカレノンの融解に由
来する％ ５０ ’Ｃ付近の吸熱ピークを示さず、６０
０℃付近にβ−シクロデキストリンに由来する融解（分
解）吸熱ピークを示す。 （ｉｌｌ 赤外線９収スペクトル（ヌジョール）におい
て、５３００．１６５０．１６１０および１０００〜１
１６０（！’に吸収を示す。 Ｏｖ） 水に極めて溶は錘い。 （２）ユビデカレノン１モルに対してβ−シクロデキス
） ＩＪン３モル以上を作用させて、次の物性を有する
ユビデカレノンのβ−シクロデキストリン包接化合物を
得ることを特徴とするユビデカレノンのβ−シクロデキ
ストリン包接化合物の製造法。 （＋） 粉末Ｘ線回折スペクトルにおいて、ユビデカ
レノンに由来する１９° および２３°付近のピークを
示さず、７°付近、１２°付近および１８°付近にピー
クを示す。 （１１）示差熱分析において、ユビデカレノンの融解に
由来する５０℃付近の吸熱ピークを示さず、５００℃付
近にβ−シクロデキストリンに由来する融解（分解）に
よる吸熱ピークを示す。 （ＩＩ） 赤外線吸収ヌベク）／Ｌ’（ヌジョール）
において、３５００．１６５０．１６１０および１００
０〜１１６０ＣＩＩ＋’に吸収を示す。 ＯＶ） 水に極めて溶は難い。 （３） 加ｅｍ解したユビデカレノンとβ〜シクロデ
キストリンの水溶液とを混合する特許請求の範囲第２槌
に記載の製造法。Scope of Claims: (1) A β-cyclodextrin clathrate compound of ubidecarenone having the following physical properties, which is obtained by reacting 3 moles or more of β-cyclodextrin with 1 mole of ubidecarenone. (1) In the powder X-ray diffraction spectrum, peaks derived from ubidecarenone near 19° and 26° are not shown, but peaks are shown near 7°, 12°, and 18°. (G) In the differential thermal analysis, no endothermic peak was observed near 50'C due to the melting of ubidecarenone, and 60%
A melting (decomposition) endothermic peak derived from β-cyclodextrin is shown near 0°C. (ill Infrared 9 absorption spectrum (Nujol), 5300.1650.1610 and 1000-1
160 (!' indicates absorption. Ov) Extremely soluble in water. (2) A β-cyclodextrin of ubidecarenone, characterized in that a β-cyclodextrin clathrate of ubidecarenone having the following physical properties is obtained by reacting 3 moles or more of IJ (β-cyclodextrin) with 1 mole of ubidecarenone. Method for producing clathrate compounds. (+) In the powder X-ray diffraction spectrum, peaks derived from ubidecarenone near 19° and 23° are not shown, but peaks are shown near 7°, 12°, and 18°. (11) In differential thermal analysis, it does not show an endothermic peak around 50°C due to melting of ubidecarenone, but shows an endothermic peak around 500°C due to melting (decomposition) of β-cyclodextrin. (II) Infrared absorption Nubek)/L' (Nujol)
In, 3500.1650.1610 and 100
Absorption is shown between 0 and 1160 CII+'. OV) Extremely difficult to dissolve in water. (3) The production method according to claim 2, in which emulsified ubidecarenone and an aqueous solution of β-cyclodextrin are mixed.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57089548A JPS58206540A (en) | 1982-05-26 | 1982-05-26 | Beta-cyclodextrin inclusion compound of ubidecarenone and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57089548A JPS58206540A (en) | 1982-05-26 | 1982-05-26 | Beta-cyclodextrin inclusion compound of ubidecarenone and its preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS58206540A true JPS58206540A (en) | 1983-12-01 |
Family
ID=13973870
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57089548A Pending JPS58206540A (en) | 1982-05-26 | 1982-05-26 | Beta-cyclodextrin inclusion compound of ubidecarenone and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58206540A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61200942A (en) * | 1985-03-04 | 1986-09-05 | Nisshin Flour Milling Co Ltd | Vitamin k2-dimethyl-beta-cyclodextrin clathrate compound |
| EP1174109A3 (en) * | 2000-07-21 | 2004-01-07 | Beiersdorf Aktiengesellschaft | Combinations of active substances respectively adducts from cyclodextrins and at least a quinone and/or at least a hydroquinone and use of such combinations of active substances in cosmetic preparations |
| WO2005035477A1 (en) * | 2003-10-08 | 2005-04-21 | Kaneka Corporation | Method of stabilizing compound having quinone skeleton and stabilized composition |
| WO2005111224A3 (en) * | 2004-05-18 | 2006-06-08 | Kemijski Inst | Water-soluble coenzyme q10 in inclusion complex with beta-cyclodextrin, process of preparing, and use thereof |
| DE102005005054A1 (en) * | 2005-02-03 | 2006-08-10 | Karl Heinz Schubert | Hydrophilic biochinone compound, process for its preparation and its use |
-
1982
- 1982-05-26 JP JP57089548A patent/JPS58206540A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61200942A (en) * | 1985-03-04 | 1986-09-05 | Nisshin Flour Milling Co Ltd | Vitamin k2-dimethyl-beta-cyclodextrin clathrate compound |
| JPH053864B2 (en) * | 1985-03-04 | 1993-01-18 | Nisshin Flour Milling Co | |
| EP1174109A3 (en) * | 2000-07-21 | 2004-01-07 | Beiersdorf Aktiengesellschaft | Combinations of active substances respectively adducts from cyclodextrins and at least a quinone and/or at least a hydroquinone and use of such combinations of active substances in cosmetic preparations |
| US6825179B2 (en) | 2000-07-21 | 2004-11-30 | Beiersdorf Ag | Active ingredient combinations or adducts of cyclodextrins and quinones |
| WO2005035477A1 (en) * | 2003-10-08 | 2005-04-21 | Kaneka Corporation | Method of stabilizing compound having quinone skeleton and stabilized composition |
| WO2005111224A3 (en) * | 2004-05-18 | 2006-06-08 | Kemijski Inst | Water-soluble coenzyme q10 in inclusion complex with beta-cyclodextrin, process of preparing, and use thereof |
| DE102005005054A1 (en) * | 2005-02-03 | 2006-08-10 | Karl Heinz Schubert | Hydrophilic biochinone compound, process for its preparation and its use |
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