Research and Development of a New Safe Form of Drugs - Aerosols: Measurement, Dosimetry, and Health Effects - page 279

Arabinogalactan (AG) of Russian larches L. sibirica and L. gmelinii is characterized by a mono-
modal curve of molecular mass distribution with a maximum within 13-18 kDa. Practicable meth-
ods have been proposed to extract high purity arabinogalactan (Tsvetaeva and Paskerova, 1962;
Antonova and Tyukavkina, 1976; Medvedeva et al., 2003, 2004). Oxidative destruction of arabi-
nogalactan derived from Siberian larch L. sibirica in water-peroxide solution under the action of
molecular oxygen made it possible to synthesize the polymeric and oligomeric products enriched
with carbonyl and carboxyl groups. Destruction proceeds with the breaking of glycoside bonds,
cycle opening and oxidation of the anomer carbon atom to carboxyl group, and detachment of
formic acid molecules in a stepwise manner (Borisov et al., 2002, 2004; Monakov et al., 2004;
Mudarisova et al., 2005).
The usage of AG as a complexing agent is relatively new. It was chosen due to its chemical com-
position, the physical and chemical properties of which resemble those of the previously studied
glycosides—GA, ST, RB.
AG complexes with various pharmacons have been obtained; in all cases, a signiicant increase
in solubility of poorly soluble substances (by 2-21 times) is observed, which demonstrates the high
effectiveness of AG as a complexing agent. All synthesized complexes were characterized by physi-
cal and chemical properties previously used for the aforementioned GA complexes.
11.2.1.15 Complexes with Arabinogalactan
Arabinogalactan and its oxidates were used for complexation of 5-aminosalicylic acid, an antitu-
berculous compound. The complexes were synthesized in the form of water-soluble amorphous
substances. The authors believe that bonding into complexes occurs due to the acid-base interaction
between the pharmacon aminogroup and carboxyl groups of oxidates. As for arabinogalactan itself,
complexation occurs through pharmacon retention in the side chains by intermolecular hydrogen
bonds and interaction of aminopharmacon with a small number of carboxyl groups, which are pres-
ent in the natural polysaccharide. As a result, complexes have been synthesized with the content
of 5-aminosalicylic acid as follows: arabinogalactan, 1.4%; polymer oxidates, 8.5%; and oligomer
oxidades, 16.0%. Pharmacon complexes with arabinogalactan and oligomer oxidades show high
in vitro activity against mycobacteria (Badykova et al., 2005, 2006).
In Dushkin et al. (2008a,b) it was shown for the irst time that the complexation effect discovered
during investigations of complexes of terpenoid glycosides with pharmacons is also manifested by
complexes of arabinogalactan as a reduction of the therapeutic dose of pharmacon and appearance
of additional positive pharmacological properties.
Complexation of AG with IM, a NSAID, tranquilizers sibazon (7-chloro-2,3-dihydro-1-methyl-
5-phenyl-1H-1,4-benzodiazepin-2-on) and mezapam (7-chloro-2,3-dihydro-1-methyl-5-phenyl-1H-
1,4-benzodiazepin), azaleptin (8-chloro-11(4-methyl-1-piperazinyl)5H-dibenzo-[b,e]-1,4-diazepin),
a neuroleptic, was studied in the three modes of complex synthesis.
The irst mode is intensive stirring of components in water solution. The second is the mechano-
chemical activation of a mixture of solid components by the method described in Shakhtshneider
and Boldyrev (1999). The third mode is the mechanochemical pretreatment of arabinogalactan
followed by the mechanochemical activation of the mixture of pharmacon with treated AG. The
samples of initial AG have unimodal molecular mass distribution with average molecular mass
of 13.5 kDa. AG treated mechanochemically is characterized by an intricate chromatogram with
several maximums in the interval of 1.2-30 kDa. The average MM value is 5 kDa. Although the
chromatographic characteristics of AG treated separately or together with pharmacon do not differ
signiicantly, the water solubility of the pharmacon is the highest in the composition of complexes
synthesized by in second mode.
It was shown that water solubility for the complexes with the AG:pharmacon having the weight
ratio of 10:1 increases for IM, sibazon, mezapam, azaleptin by 9.9, 2.4, 19.1, and 20.5 times, respec-
tively. For complexes of AG: pharmacon 20:1 these values are as follows: IM, 16.8; sibazon, 3.0;
mezapam, 46.8; azaleptin, 38.8. All modes of complex synthesis have to be compared in terms of