Environmental Engineering Reference
In-Depth Information
TABLE 11.3
Acute Toxicity of Complexes GA with 
NSAID in Mice (Per os)
LD 50  (mg/kg)
Pharmacon
Drugs
LD 50  (mg/kg)
GA:ASA (1:1)
4500
1900
GA:OF (1:1)
1750
310
GA:BD (1:1)
3150
880
GA:AN (1:1)
8000
570
Complexes with GA have less irritant effect on the mucous coat of stomach as compared with
original NSAID. Thus, complex GA:ASA stimulates ulcerous lesions reparation and complex GA:OF
shows low ulcerogenic activity. Both complexes decrease the level of prostaglandins E 1 and E 2 in the
blood of animals with chronic inlammation. The complexes can be recommended as anti-inlamma-
tory drugs for clinical trials, including the trial in patients with stomach and duodenal ulcers.
Acute toxicity of GA complexes with NSAID is 2-14 times lower as compared with original
drugs (see Table 11.3) (Baltina et al., 1991b, 1992; Bondarev et al., 1991; Tolstikov et al., 1991a).
Complexation of IP with glycyrrhizic acid by the mechanochemical method allows lowering the
dose by 10 times while preserving the high analgetic activity, but only in the model of chemical
irritation of peritoneum. This also demonstrates the preservation of its anti-inlammatory activity
for this pharmacon in the complex.
At the complexation of NSAID with GA synergetic effect can be observed, manifested by an
increase in water-solubility and biological activity and simultaneous decrease of toxicity and ulcero-
genic action on gastrointestinal tract. Comparative study of pharmacological activity of molecu-
lar complexes GA:ASA and GA:OF synthesized by the solution and mechanochemical methods
showed that solid-phase synthesis opens an economical and technologically more suitable way of
making highly effective NSAI drugs (Dushkin et al., 2001).
11.2.1.4   Complexes of Prostaglandins with Glycyrrhizic 
Acid as a New Group of Uterine Tonics
Prostaglandins have been widely used in medicine and veterinary practice due to their ability to
stimulate uterine muscles in small doses.
The use of prostaglandin in veterinary practice is one of the most important advantages of pros-
taglandin studies. Prostaglandin derivatives are widely used in pigs try to synchronize farrowing.
Prostaglandins are also highly effective in preparing cows and mares for artiicial insemination.
Introduction of prostaglandin drugs helped to resolve the problems of postpartum complications in
cows and mares.
Cloprostenol is one of the main drugs used in veterinary practice. Along with other prostaglan-
dins, it is obtained by multistage synthesis, which results in high prices of the drug. The reduction
of therapeutic active dose is an important task. Besides, it is necessary to increase the stability of
labile prostaglandins in the inished drugs.
Both problems were successfully resolved by the complexation of prostaglandins with GA. GA
complexes with prostaglandins of the E and F series (PGE 1 , PGE 2 ,PGF , sulprostone [SP] and
cloprostenol) were obtained and investigated.
Unlike the initial prostanoids, the complexes synthesized by the solution method in the form of
water-soluble amorphous substances are highly stable both in solid state and in solutions (Tolstikov
et al., 1991c). Complexation has been proved by spectral analysis methods and chromatographic
homogeneity.
 
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