Environmental Engineering Reference
In-Depth Information
Nowadays, in medicinal chemistry rapidly develops the area that is dedicated to the improvement
of well-known drugs properties by complexation with different synthetic and plant compounds.
Such complexation results in the drug's water-solubility enhancement, bioavailability improvement,
and stability increase. There are many examples of such complexing compounds, for instance,
cyclodextrins, PEG, pectin, and chitosan.
One of the promising approaches in this area is the usage of carbohydrate-containing plant
metabolites as a complexing agent. Striking examples of such agents are glycyrrhizic acid derived
from licorice root and arabinogalactan that contains up to 12%-15% in wood of larches
Larix sibir-
ica
and
Larix gmelinii
. Other interesting agents are the metabolites of South American plant
Stevia
rebaudiana
Bertoni stevioside and rebaudiside A. The important advantages of the aforementioned
compounds are their low toxicity (LD
50
> 5000 mg/kg), ability to form complexes, and huge amount
of raw materials suitable for their industrial isolation.
Aforesaid compounds have been used to synthesize complexes with different well-known drugs.
This chapter describes the results of pharmacological investigation of these compounds.
11.2.1.1 Glycyrrhizic Acid
18βH-glycyrrhizic acid (GA) (Figure 11.17), a triterpene glycoside produced by widespread plants,
Fabaceae
Glycyrrhiza glabra
L.,
Glycyrrhiza uralensis
Fisch, and
Glycyrrhiza korshinskyi
Grig
(licorice), is one of the few plant metabolites combining availability with a unique variety of pharma-
cological activities (Baltina, 2003; Tolstikov et al., 1997a, 2007a). Glycyrrhizic acid, the molecule of
which consists of hydrophobic (aglycon) and hydrophilic (carbohydrate chain) parts, manifests the
properties typical for micelle-forming substances (James et al., 1962; Gilbert and James, 1964; Azaz
and Segal, 1980; Kondo et al., 1986; Maskan, 1999; Romanenko and Murinov, 2001). According to
Azaz and Segal (1980), the micellar critical concentration (MCC) of GA water solution is 10
−3
M.
The study of rheological properties of GA solutions by the viscometric method resulted in a conclu-
sion that their properties were similar to those of Newton liquids (Romanenko and Murinov, 2001).
The solution viscosity at the concentration lower than 3 × 10
−5
M does not change. With increase of
the concentration above that for MCC (>3 × 10
−5
M) the solution viscosity and turbidity increase.
Thus, GA associates existing in water solution start to group into micelles. When ethanol is added
to water solution, at 20 volume percent of ethanol MMC increases to 10
−4
M. Apparently, the pres-
ence of ethanol prevents micelle formation at GA concentration ranging from 3 × 10
−5
to 1 × 10
−4
M.
GA association in solutions was studied by NMR methods (Kornievskaya et al., 2008). In NMR
spectra of H
1
for water-methanol solutions (20% MeOH) as GA concentration increases, the lines of
methyl groups corresponding to aglycone broaden. The authors suggest that this is due to substan-
tial change of the relaxation time of GA methyl protons, which is caused by the formation of larger
structures as the concentration increases. Using pulse NMR-spectroscopy, the spin-spin relaxation
of GA methyl protons depending on GA concentration in the solution was investigated. The experi-
mental data indicate that small micelles with aggregation number
M
≤ 10 may form. This applies to
CO
2
H
H
O
CO
2
H
O
O
OH
OH
O
HO
2
C
O
OH
OH
OH
FIGURE 11.17
18βH-glycyrrhizic acid.
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