Mihály Pósa,1 Valéria Guzsvány,2 János Csanádi,2,* Júlia Borbás2 and Ferenc Gaál2
1 Laboratory of Physical Pharmacy, Department of Pharmacy, Faculty of Medicine,
University of Novi Sad,
Hajduk Veljkova 3, 21000 Novi Sad, Republic of Serbia,
2 Department of Chemistry, Faculty of Sciences, University of Novi Sad, Trg
Dositeja, Obradovića 3,
21000 Novi Sad, Republic of Serbia
* Corresponding author: E-mail: jcanadi@uns.ac.rs
Tel.: +381214852773
Abstract
12-Monoketocholic acid (12-MKC) shows a promotive effect in the transport of
some drugs (lidocaine, morphine, quinine,
gliclazide, etc.). In the mechanism of pharmacological action of 12-MKC an
important role plays its aggregation
(self-association), as well as formation of mixed micelles. These phenomena were
studied by the 1H NMR spin-lattice
relaxation method using solutions of sodium salt of 12-MKC in D2O and in D2O
solution saturated with 1-octanol. The
function describing the dependence of the spin-lattice relaxation time (T1) on
the concentration of Na-12-MKC (cBA) in
D2O has one inflexion point (at the concentration of 48 mM), whereas the same
function for the saturated solution of 1-
octanol has two inflexion points (one at the concentration of 45 mM and the
other at 87 mM). These differences in the
curves T1 = f(cBA), as well as the shift of the solubilization curve of lecithin
in the presence of 1-octanol towards higher
concentrations of Na-12-MKC, indicate that sodium salt of this keto-bile acid
forms mixed micelles with 1-ocatnol, so
that the application of the micellar solution of Na-12-MKC in the presence of
1-octanol decreases membrane toxicity
(membrane lysis) of this bile acid. The curves T1 = f(cBA) for methyl esters of
12-MKC and cholic acid in the CDCl3 solution
have one inflexion point at the concentration above 5 mM, indicating formation
of the micelles of Small’s type,
whereas methyl ester of 3,7,12-triketocholic acid forms a gel-like structure.
Keywords: 12-monoketocholic acid, 1H NMR relaxation method, aggregation