JP2792061B2 - Capillarycin production method - Google Patents
Capillarycin production methodInfo
- Publication number
- JP2792061B2 JP2792061B2 JP29609688A JP29609688A JP2792061B2 JP 2792061 B2 JP2792061 B2 JP 2792061B2 JP 29609688 A JP29609688 A JP 29609688A JP 29609688 A JP29609688 A JP 29609688A JP 2792061 B2 JP2792061 B2 JP 2792061B2
- Authority
- JP
- Japan
- Prior art keywords
- water
- extract
- organic solvent
- insoluble organic
- solvent
- 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
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- Pyrane Compounds (AREA)
Description
【発明の詳細な説明】 ［産業上の利用分野］ 本発明は医薬品として有用なキャピラリシンの効率的
かつ安価な製造法に関するものである。本発明に係る製
造法は文献未記載の新規な方法であって、キャピラリシ
ンおよびその誘導体を医薬品として工業的規模で製造す
るために有用である。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an efficient and inexpensive method for producing capillaryricin useful as a pharmaceutical. The production method according to the present invention is a novel method that has not been described in any literature, and is useful for producing capillaricin and its derivatives as pharmaceuticals on an industrial scale.
［従来の技術および課題］ キャピラリシンは下記式で表されるクロモンであり、
その薬理作用として利胆作用、肝障害改善作用が認めら
れている。またアルドースリダクターゼ阻害作用を有す
ることから、糖尿病の合併症に有効な化合物としても期
待されている（昭和63年特許願53551号（特開平１−228
914号））。[Prior art and problems] Capillaricin is a chromone represented by the following formula,
Its pharmacological effects include a bile effect and a liver ameliorating effect. In addition, since it has an aldose reductase inhibitory activity, it is also expected to be an effective compound for complications of diabetes (Japanese Patent Application No. 53551/1988 (Japanese Unexamined Patent Publication No. 1-228)
914)).
このようにキャピラリシンは、医薬として非常に有用
であると考えられているにもかかわらず、現在までキャ
ピラリシンの製造に関して効果的な化学的合成方法の報
告例はない。また天然物からの抽出法においては、アル
コール類で熱抽出した後、カラムクロマトグラフィーを
用いる方法や超臨界抽出法等が報告されているが、いず
れも低収率でコストが高く実際的な製造法ではない。 As described above, although capillarisin is considered to be very useful as a medicine, there is no report of an effective chemical synthesis method for the production of capillarisin to date. In addition, in the extraction method from natural products, methods such as column extraction and supercritical extraction after heat extraction with alcohols have been reported. Not a law.
そこでキャピラリシンおよびその誘導体の医薬への応
用を可能にするために、より効率的で安価にピラリシン
を製造する方法が求められていた。Therefore, in order to enable the application of capillarisin and its derivatives to medicines, there has been a demand for a more efficient and inexpensive method for producing pyraricin.
［課題を解決するための手段］ 本発明者等はいかにして簡便かつ安価に、更に効率よ
くキャピラリシンを得るかについて鋭意検討を重ねた結
果、キャピラリシン含有植物の抽出液をアルカリおよび
ホウ酸塩水溶液で処理することにより、上記課題が解決
できることを見いだし、本発明を完成するに至った。[Means for Solving the Problems] The present inventors have conducted intensive studies on how to obtain capillary ricin easily, inexpensively, and more efficiently. As a result, the extract of the capillary lysine-containing plant was extracted with alkali and boric acid. The inventors have found that the above-mentioned problems can be solved by treating with a salt aqueous solution, and have completed the present invention.
すなわち本発明は、キャピラリシン含有植物を、水不
溶性有機溶媒を用いて抽出し、抽出液をアルカリ処理
後、水層を中和し、生成した沈澱物を水不溶性有機溶媒
で抽出し、該抽出液をホウ酸塩水溶液で分配し、該水不
溶性有機溶媒層よりキャピラリシンを得ることを特徴と
するキャピラリシンの製造法である。That is, the present invention provides a method for extracting a capillaricin-containing plant using a water-insoluble organic solvent, treating the extract with an alkali, neutralizing the aqueous layer, extracting the resulting precipitate with a water-insoluble organic solvent, and extracting the extract. A method for producing capillary lysine, comprising distributing a liquid with an aqueous borate solution and obtaining capillary lysine from the water-insoluble organic solvent layer.
以下に本発明を詳細に述べる。 Hereinafter, the present invention will be described in detail.
抽出にあたって原料となるキャピラリシンを含有する
植物の具体例としては、例えばキク科のカワラヨモギ
（Artemisia Capillaris）が挙げられ、全草、花蕾、葉
のいずれを用いてもよく、また乾燥、切砕などした加工
品でもよい。Specific examples of plants containing capillarisin as a raw material for extraction include, for example, Artemisia Capillaris of the Asteraceae family, and any of whole plants, flower buds and leaves may be used, and drying, cutting, etc. Processed products may be used.
なお、カワラヨモギの花穂は生薬 （Artemisiae Capillaris Flos）として知られている
が、この を原料としてもよいことは言うまでもない。In addition, the spikes of sagebrush are crude drugs (Artemisiae Capillaris Flos) Needless to say, it may be used as a raw material.
水不溶性有機溶媒とは、水と混和しない極性溶媒であ
ればよく、その具体例としては、酢酸ブチル、酢酸エチ
ル、酢酸メチルなどのエステル類、クロロホルム、塩化
メチレン等のハロゲン化炭化水素、またはエーテル類等
が挙げられるが、酢酸エチルが最適である。The water-insoluble organic solvent may be any polar solvent that is immiscible with water, and specific examples thereof include butyl acetate, ethyl acetate, esters such as methyl acetate, chloroform, halogenated hydrocarbons such as methylene chloride, and ethers. But ethyl acetate is most suitable.
この工程において水不溶性有機溶媒を用いることによ
り、余分な糖類や水溶性極性物質の抽出を押さえ、また
抽出液を直接アルカリ水溶液と分配して弱酸性物質であ
るキャピラリシンを水層に移すことが容易にでき、従来
のように一度溶媒を留去する手間が省け、連続して操作
ができる。By using a water-insoluble organic solvent in this step, the extraction of excess saccharides and water-soluble polar substances can be suppressed, and the extract can be directly distributed with an aqueous alkali solution to transfer the weakly acidic substance, capillaricin, to the aqueous layer. It can be easily performed, and the operation of removing the solvent once as in the related art can be omitted and the operation can be continuously performed.
水不溶性溶媒の使用量は溶媒の種類や抽出条件により
異なるが、原料重量の２〜15倍量の溶媒を用い、一例を
挙げると （市場品）1kgに対しては約４を用いるのが適当であ
る。また、この溶媒は回収して繰り返し用いることがで
きる。The amount of the water-insoluble solvent varies depending on the type of the solvent and the extraction conditions, but the solvent is used in an amount of 2 to 15 times the weight of the raw material. (Market product) It is appropriate to use about 4 for 1 kg. This solvent can be recovered and used repeatedly.
抽出時間は通常約１日から４日程度であるが、１日放
置するだけでも十分である。抽出操作は一度に行っても
よいし、数度にわたって行ってもよい。また、抽出温度
は室温で十分であり、従来のように加熱を必要としない
が、使用する溶媒の沸点までの温度に加熱をしても差し
支えない。The extraction time is usually about 1 to 4 days, but it is sufficient to leave it for 1 day. The extraction operation may be performed at once or may be performed several times. Although the extraction temperature is sufficient at room temperature and does not require heating as in the prior art, heating to a temperature up to the boiling point of the solvent to be used may be performed.
抽出後は適宜抽出液を濃縮した後、抽出物中の中性お
よび塩基性物質を除去するためアルカリ処理を行う。After the extraction, the extract is appropriately concentrated and then subjected to an alkali treatment to remove neutral and basic substances in the extract.
アルカリ処理に用いられるアルカリとしては、例えば
炭酸カリウム、炭酸ナトリウム等が挙げられ、そのpHは
12前後が適当であり、直接分配することにより抽出物中
の中性および塩基性物質を除去することができる。Examples of the alkali used in the alkali treatment include potassium carbonate, sodium carbonate, and the like.
Around 12 is appropriate, and neutral and basic substances in the extract can be removed by direct distribution.
中和は塩酸、硫酸等の鉱酸を水層に添加すればよい。 For neutralization, a mineral acid such as hydrochloric acid or sulfuric acid may be added to the aqueous layer.
水層を中和することにより生じた沈澱物を水不溶性有
機溶媒を用いて抽出するが、水不溶性有機溶媒の具体例
は前述と同様である。The precipitate generated by neutralizing the aqueous layer is extracted using a water-insoluble organic solvent. Specific examples of the water-insoluble organic solvent are the same as described above.
次にこの抽出液をホウ酸塩水溶液で分配する。ホウ酸
塩としては、メタホウ酸ナトリウム、メタホウ酸カリウ
ム、ホウ砂等が挙げられるが、メタホウ酸ナトリウムが
最適である。The extract is then partitioned with an aqueous borate solution. Examples of the borate include sodium metaborate, potassium metaborate, and borax, with sodium metaborate being most suitable.
分配後の水不溶性有機溶媒より溶媒を留去して得られ
た残渣を適当な溶媒を用いて結晶化させてキャピラリシ
ンを得る。このキャピラリシンの純度を更に向上させる
ためには再結晶が好ましく、結晶化および再結晶に用い
る溶媒としては、アセトン、酢酸エチル、アセトニトリ
ル等が挙げられるが、アセトニトリルが最適である。The residue obtained by evaporating the solvent from the water-insoluble organic solvent after partitioning is crystallized using an appropriate solvent to obtain capillaricin. Recrystallization is preferable to further improve the purity of the capillary lysine. As a solvent used for crystallization and recrystallization, acetone, ethyl acetate, acetonitrile and the like can be mentioned, and acetonitrile is most preferable.
［発明の効果］ 本発明の効果としては、従来のシリカゲルを用いたカ
ラムクロマトグラフィーを利用する方法と比較して操
作が簡便であり、安価であり、高収率でキャリラリ
シンを得ることができる。[Effects of the Invention] As the effects of the present invention, calilaricin can be obtained in a simple operation, at low cost, and in a high yield as compared with a conventional method utilizing column chromatography using silica gel.
従って、本発明のキャピラリシンの製造法は、医薬品
として有用なキャピラリシンを製造するには好適なもの
である。Therefore, the method for producing capillary ricin of the present invention is suitable for producing capillary ricin useful as a pharmaceutical.
以下に実施例を示して本発明を更に詳細に説明する
が、本発明はこれにより何ら制限されるものではない。Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.
実施例１ （市場品）2.0kgに酢酸エチル８を加え、４日間浸漬
した。これを濾過後、残渣に再度酢酸エチル６を加え
４日間放置後濾過し、濾液を減圧濃縮した後、両濾液を
合わせ10％炭酸カリウム２で３回抽出した。抽出液に
10％塩酸３を加えて中和した後、不溶物を酢酸エチル
２で３回抽出した。抽出液に0.2Mメタホウ酸ナトリウ
ム水溶液1.8を加え、抽出液を洗った後水洗し、飽和
食塩水および無水硫酸ナトリウムで乾燥した。酢酸エチ
ルを留去し、あめ状残渣16.8gを得た。この残渣をアセ
トニトリルを用いて結晶化させ、無色プリズム晶3.2gを
得た。この無色プリズム晶の理化学的性質は文献［薬学
雑誌,96（７）,841（1976）］記載のキャピラリシンの
それと一致した。Example 1 (Market product) Ethyl acetate 8 was added to 2.0 kg and immersed for 4 days. After filtration, ethyl acetate 6 was added to the residue again, and the mixture was allowed to stand for 4 days, followed by filtration. The filtrate was concentrated under reduced pressure, and both filtrates were combined and extracted three times with 2% 10% potassium carbonate. To extract
After adding 10% hydrochloric acid 3 for neutralization, the insolubles were extracted three times with ethyl acetate 2. The extract was added with a 0.2 M aqueous sodium metaborate solution (1.8), and the extract was washed, washed with water, and dried over saturated saline and anhydrous sodium sulfate. Ethyl acetate was distilled off to obtain 16.8 g of a syrupy residue. The residue was crystallized using acetonitrile to obtain 3.2 g of colorless prism crystals. The physicochemical properties of the colorless prisms were consistent with those of capillarisin described in the literature [Pharmaceutical Journal, 96 (7), 841 (1976)].
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 Ｐｈｙｔｏｃｈｅｍｉｓｔｒｙ，23 ［９］ （1984）Ｐ．1885−1888 Ａｒｃｈ．Ｂｉｏｃｈｅｍ．Ｂｉｏｐ ｈｙｓ．，239［２］ （1985）Ｐ．491 −496 (58)調査した分野(Int.Cl.6，ＤＢ名) C07D 311/54 ＣＡ（ＳＴＮ)──────────────────────────────────────────────────続 き Continuation of the front page (56) References Phytochemistry, 23 [9] (1984) 1885-1888 Arch. Biochem. Biops. , 239 [2] (1985) p. 491 -496 (58) Field surveyed (Int. Cl. 6 , DB name) C07D 311/54 CA (STN)
Claims (1)
溶媒を用いて抽出し、抽出液をアルカリ処理後、水層を
中和し、生成した沈澱物を水不溶性有機溶媒で抽出し、
該抽出液をホウ酸塩水溶液で分配し、該水不溶性有機溶
媒層よりキャピラリシンを得ることを特徴とするキャピ
ラリシンの製造法。(1) extracting a capillarisin-containing plant with a water-insoluble organic solvent, treating the extract with an alkali, neutralizing the aqueous layer, extracting the resulting precipitate with a water-insoluble organic solvent,
A method for producing capillary lysine, comprising partitioning the extract with an aqueous borate solution and obtaining capillary lysine from the water-insoluble organic solvent layer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29609688A JP2792061B2 (en) | 1988-11-25 | 1988-11-25 | Capillarycin production method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29609688A JP2792061B2 (en) | 1988-11-25 | 1988-11-25 | Capillarycin production method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02142781A JPH02142781A (en) | 1990-05-31 |
| JP2792061B2 true JP2792061B2 (en) | 1998-08-27 |
Family
ID=17829076
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29609688A Expired - Lifetime JP2792061B2 (en) | 1988-11-25 | 1988-11-25 | Capillarycin production method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2792061B2 (en) |
-
1988
- 1988-11-25 JP JP29609688A patent/JP2792061B2/en not_active Expired - Lifetime
Non-Patent Citations (2)
| Title |
|---|
| Ａｒｃｈ．Ｂｉｏｃｈｅｍ．Ｂｉｏｐｈｙｓ．，２３９［２］ （１９８５）Ｐ．４９１−４９６ |
| Ｐｈｙｔｏｃｈｅｍｉｓｔｒｙ，２３［９］ （１９８４）Ｐ．１８８５−１８８８ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02142781A (en) | 1990-05-31 |
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