Process for preparation of dibenzocyclooctadiene type lignan

Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Conjugate or complex

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426655, 514 22, A61K 3578, A61K 3170, A23L 128

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054845955

DESCRIPTION:

BRIEF SUMMARY
DESCRIPTION

1. Technical Field
The present invention relates to a process for the preparation of dibenzocyclooctadiene type lignan which is valuable as a medicine.
2. Background Art
It is generally known that many dibenzocyclooctadiene type lignans are effective as medicines. For example, it is known that schizandrin comprises analgesic action, gomisin A and gomisin C comprise liver trouble-moderating action, and deoxyschizandrin exhibits anti-ulcer action.
It is known in the art to obtain dibenzocyclooctadiene type lignans from plants to treat plant extracts containing said lignans to chromatography using as the adsorbent, for example, silica gel, ODS silica gel, alumina, Celite or a porous polymer gel such as Dia-Ion HP-20 repeatedly to effect purification. But the process comprising subjecting a plant extract containing large quantities of impurities directly to the chromatography is defective as an industrial preparation process because a large quantity of the adsorbent must be used, the deterioration speed of the adsorbent is high, and a large quantity of the solvent must be used for the chromatography. To use a specific dibenzocyclooctadiene type lignan as a medicine, it is necessary to prepare this lignan in a large quantity, and therefore, a simple process capable of providing an intended lignan in a large quantity is desired.


Disclosure of the Invention

The inventors carried out research with a view to developing a process capable of providing a large quantity of a dibenzocyclooctadiene type lignan by simple means, and as a result, found that, if the partition extraction method is adopted, the amounts of the adsorbent and solvent used for the chromatography can be greatly reduced and an intended dibenzocyclooctadiene type lignan can be very simply prepared in a large quantity. The present invention is based on this finding.
More specifically, in accordance with the present invention, there is provided a process for the preparation of a dibenzocyclooctadiene type lignan, which comprises extracting a plant containing a dibenzocyclooctadiene type lignan with a low polar solvent, subjecting the resulting extract to the partition extraction using a water-insoluble low polar solvent and a water-soluble high polar solvent at least one time, and recovering the dibenzocyclooctadiene type lignan from the layer of the water-soluble high polar solvent.


Best Mode of Carrying Out the Invention

As the dibenzocyclooctadiene type lignan-containing plant to be extracted in the present invention, there can be mentioned plants belonging to the family Schisandraceae, such as Schisandra chinensis Baill., Schisandra sphenathera Rehd. et Wils., Schisandra rubriflola and Kadsura japonica.
As specific examples of the low polar solvent valuably used in the present invention, there can be mentioned petroleum ether, n-hexane, n-heptane, benzene, toluene and cyclohexane. The extraction is carried out at a temperature in the range of from room temperature to the boiling point of the used solvent, preferably under heating.
Then, the extract is subjected to the partition extraction (hereinafter referred to as "partition") using a water-insoluble low polar solvent and a water-soluble high polar solvent. If the solvent used for the partition is the same as the solvent used for the extraction, then preferably the partition is carried out after the extract has been condensed at an appropriate concentration or dried. If the solvent used for the partition is different from the solvent used for the extraction, preferably the partition is carried out after the extract has been dried.
As specific examples of the low-polarity water-insoluble solvent, there can be mentioned petroleum ether, n-hexane, n-heptane, benzene, toluene and cyclohexane, and as the high-polarity water-soluble solvent, there can be mentioned methanol and ethanol. The proportion of the high-polarity water-soluble solvent in the solvent is preferably from 40 to 80%, most preferably from 55 to 65%. The partition can be performed by customary procedures.
The partit

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