Narcissus and Daffodil

412 J.R. Murray
occurs in a two-phase liquid system comprising aqueous base and organic solvent
of dielectric constant of less than 4.8. The process improves the yield of sufficiently
pure products in the organic phase to allow recovery by evaporation, avoiding
relatively expensive chromatographic purification. These products can then readily
be converted to corresponding galanthamine structures (Henshilwood and Johnson,
1996). Other filings from the same group describe asymmetric transformation of
racemic narwedine-type compounds by reacting these racemates with an enantiomerically
enriched acid to form a diastereomeric salt (Chaplin et al., 1997b).
A method for ‘easily’ preparing narwedine, lycoramine, norgalanthamine and
sanguinine by the preparation of intramolecularly coupled compound comprising
of a phenol derivative with a supervalent iodine reagent is described elsewhere
(Dyer et al., 1996). As far as galanthamine itself is concerned, similar techniques
can be used to prepare specific enantiomers, for example by seeding a supersaturated
solution of racemic galanthamine salt with an enantiomerically enriched
form of the salt, with or without the utilisation of an achiral counter-ion (Kagaku
Gijutsu Shinko Jigyodan, 1999).
Of particular interest, as it has already led to a commercially available source of
galanthamine, is an Austrian patent which embraces methods of producing new or
known galanthamine products from benzaldehyde and phenethylamine derivatives.
By reacting these together and reducing the product, an N-benzylphenylamine
derivative is formed. This is then subjected to oxidative cyclisation and the
product is then reduced (Tiffen, 1997).
A fascinating method of ‘feeding’ galanthamine precursors (derivatives) to plant
extract to allow the enzymatic conversion by the plant material of the oxidative
cyclisation precursor, is described. The object is to enhance yields of optically pure
forms over and above those expected from straightforward extraction techniques
(Czollner et al., 1995).
Formulation patents
These patents fall into two categories – those related to combination therapy and
those describing galenic presentation forms.
The combination of an acetyl-cholinesterase inhibitor with a muscarinic agonist
(citing galanthamine as one of the preferred cholinesterase inhibitors with a variety
of possible muscarinic agonists quoted) has been claimed to be useful in treating
central and peripheral nervous system diseases (Bannister and McCague, 1997).
A fast-dissolving galanthamine hydrobromide tablet is the subject of published
patent applications. The tablet includes a spray-dried mixture of lactose monohydrate
and microcrystalline cellulose (75:25) as a diluent with a new disintegrant
(Callahan and Schwarz, 1999).
Transdermal delivery of galanthamine is claimed to give better control of
release of drug over a longer period of time (at least 24 hours), steadier serum levels
and higher therapeutic effects at lower dosages with better patient acceptability
(De Conde and Gilis, 1997). The system utilises a reservoir layer of active agent in
a polymer matrix plus a penetration enhancer. This homogenous reservoir
mixture is coated onto a backing layer and then covered with a protective layer.
Interestingly, the same company has filings around the recovery of the active
agent from unused or discarded transdermal therapeutic systems using solvent