Research and Development of a New Safe Form of Drugs - Aerosols: Measurement, Dosimetry, and Health Effects - page 274

According to our observations, buspirone and BSP: GA did not inluence the content of choles-
terol and triglyceride in the blood of anxious-depressive mice either (Table 11.6). Therefore, the
chronic introduction of buspirone and BSP: GA does not affect the markers of lipid exchange.
One of the nonspeciic factors determining the functional changes during social stress is the
increase in lipid peroxidation (LP) and the responsive activation of the body's antioxidant system,
an important component of which is the catalase ferment (Pshennikova, 2000). Avgustinovich et al.
(2003) had previously observed the decrease in catalase activity in anxious-depressive mice. The dis-
covered and conirmed increase in catalase activity during the chronic introduction of buspirone and
BSP: GA complex, as well as the decrease in malondialdehyde (MDA) content in the group of animals
with buspirone introduction (Table 11.6), proves the activation of the antioxidant system in “sick”
animals. Considering that buspirone is primarily used as an anxiolytic drug, one may suspect the
involvement of the LP mechanisms in the process of the anxious status formation in mammals. It is
especially important that an equally strong effect is observed in cases of both buspirone and its com-
plex with GA, in which the buspirone content is essentially 10 times lower. It shows that the usage of
BSP: GA complex may prove more effective than that of buspirone, and that it may serve as a method
of reduction of the side effects observed during the prolonged introduction of the anxiolytic to patients.
11.2.1.8 Complexes of Glycyrrhizic Acid with Antitumor Drugs
Synthesis by the solution method of complexes of glycyrrhizic acid with 5-luorouracil, luorofur, and
rubomicine hydrochloride with composition 1:1 is described in (Baltina et al., 2003). Composition
of the complexes, which are chromatographically homogeneous amorphous substances, was proved
by spectral methods. Complexation resulted in water solubility and lower toxicity. The complex of
luorofur has an antitumor action on Pliss lymphosarcoma, melanoma B-16, and Heren's carcinoma.
The eficiency indices for these diseases are equal to 3.05, 2.11, and 1.7, respectively. Inhibition of
growth for these tumors is 67.2%, 53.4%, and 87.1%, respectively.
11.2.1.9 Complexes of Glycyrrhizic Acid with Antimicrobial Drugs
The 1:1 complexes of GA with antibiotics such as levomycetin, sulfapyridazin, sulfadimethoxine,
sulfamonomethoxine, sulfadimesine, sulgin, sulfanilamides; and drugs isoniaside and furacillin
were synthesized by the solution method. All the complexes are chromatographically homogeneous
amorphous substances; complexation is proved by IR spectral data indicating that the spectral lines
of hydroxylic and carbonylic groups are shifted to the short-wave band.
Comparative data are available on the antimicrobial action of the complexes. In staphylococcosis,
on the 10th day after contagion the survival rate was the highest (90%) in the group of animals receiv-
ing the complex of GA with levomycetin at the dose of 50 mg/kg. In the group receiving only levo-
mycetin the survival rate was 30%. The survival rate among the animals infected with Pseudomonas
aeruginosa , Proteus vulgaris , and Escherichia coli was about 80% in the group receiving the com-
plex. In the group receiving levomycetin the survival rate ranged between 20% and 50%. The com-
plex was shown to be able to stimulate humoral and cellular immunity (Kondratenko et al., 2003).
11.2.1.10 Complexation with Hypocholesterolemic Agent Symvastatin
The inhibitors of 3-hydroxi-3-methylglutaril-CoA reductase (3HMG-CoA reductase), so-called
statins, are known as eficacious drugs lowering low-density lipoprotein secretion, which explains
their wide use in anti-atherosclerosis therapy. At the same time, most statins are known to have
side effects. That is why the development of safer drugs with a prolonged action is a present-day
necessity. An NMR study of symvastatin (SMS) behavior in solutions in the presence of GA led
to a conclusion on the formation of stable complexes. Complex GA: SMS = 4:1 was synthesized,
which demonstrated stability in water solutions at GA concentration more than 0.2 mM (Tolstikov
et al., 2007b). The complex patented under the name “symvaglysine” (SMG) (Vavilin et al., 2008)
showed 3HMG-CoA reductase noncompetitive inhibiting activity. Effective at the doses containing