Method for producing an extract containing artemesinin

Details Method for producing an extract containing artemesinin Method for producing an extract containing artemesinin

1999-03-31

2001-01-30

Tate, Christopher (Department: 1651)

Drug, bio-affecting and body treating compositions

Antigen, epitope, or other immunospecific immunoeffector

Conjugate or complex

C514S450000, C549S348000

Reexamination Certificate

active

06180105

ABSTRACT:

This invention relates to the production of a novel extract from
Artemisia annua
which contains high levels of the known anti-malarial active Artemisinin. The invention also relates to a method of producing such an extract.
Artemisia annua
has been used in China for many centuries for the treatment of malaria. Research in the 1970s by Chinese scientists confirmed the efficacy of preparations of
Artemisia annua
in the treatment of malaria, including the most severe and life threatening form of the disease known as cerebral malaria, caused by infection with the Plasmodium falciparum parasite. The main chemical constituent of Artemisia responsible for this pharmacological activity was identified as the unusual bridged peroxy sesquiterpene structure originally named “Qinghaosu” but now known as artemisinin. The structure of artemisinin is given below:
Clinical studies on artemisinin and semi-synthetic derivatives such as artemether have confirmed the efficacy of this type of compound in the treatment of malaria. Artemisinin lacks the nitrogen containing heterocyclic ring that is common to the standard anti-malarials currently used such as the aminoquinolines (quinine, chloroquine, primaquine, etc.) The problem of resistance and cross-resistance that is now beginning to seriously limit the effectiveness of these drugs is not observed for artemisinin. For example, artemisinin has been found to be effective against chloroquine resistant strains of
Plasmodium falciparum.
Artemisinin has recently been prepared synthetically but such is the complexity of the molecule that there is no large scale economical synthetic route. This has been recognized by the vigorous research effort directed towards the synthesis of much simpler analogues of artemisinin.
Chinese researchers in their earlier studies favored extracts of Artemisia produced using non-polar organic solvents such as diethyl ether or more commonly, petroleum ether. However, these have the drawbacks that the artemisinin content was quite low and that it was difficult to completely remove trace levels of the solvent to produce a pharmaceutically acceptable product. The extraction process uses large quantities of organic solvent which must either be disposed of or recycled.
In recent years, the use of liquefied carbon dioxide extraction has been applied to the isolation of pharmaceutical actives from plant materials. This technique has been used on an industrial scale for over two decades for the extraction of flavor principles from hops and other herbs and spices. It has the advantage over extraction with conventional organic solvents that the extraction medium is readily and completely removed simply by depressurizing the extraction apparatus, thus allowing the liquid carbon dioxide to vaporize into the atmosphere. Thus, problems of waste solvent disposal and trace solvent contamination of finished product are eliminated. The selectivity of liquid carbon dioxide is generally superior to organic solvents of comparable polarity such as ethyl acetate or petroleum ether.
According to a first aspect of the present invention, a method of preparation of an artemisinin extract comprises the steps of extraction of
Artemisia annua
with solvent comprising liquid carbon dioxide and allowing the carbon dioxide to evaporate from the resultant mixture.
According to a second aspect of the present invention, there is provided an
Artemisia annua
extract containing more than 10% by weight of artemisinin, the extract not containing any residual organic solvent.
A co-solvent may be employed, for example a polar hydroxylic solvent such as C
1
to C
4
alcohol, preferably ethanol. An amount of co-solvent of 5 to 20%, preferably 10% by weight may be employed.
The resultant residual extract may have a high artemisinin content without any traces of residual non-hydroxylic solvent.
Preferred methods involve extraction at a pressure of 1500 to 4500 psi (100 to 310 bars), preferably about 1500 psi (100 bars) and at a temperature in the region of 20 to 50° C., preferably 25 to 30° C. Use of sub-critical carbon dioxide without any co-solvent is preferred.


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