Bile acid preparations

B Fritzsch, RHH Neubert, G Dongowski, L Heinevetter. Interactions between food components and drugs—part 8 effect of pectins and bile acid preparations forming stable mixed micelles on transport of quinine in vitro. Pharmazie 55 59-61, 2000. 

Slightly hindered hydroxyl groups of bile acids can be silylated according to the procedure of Makita and Wells [319] methyl esters of bile acids, prepared by treatment with diazomethane, are dissolved in anhydrous pyridine (ca. 1 ml per 10 mg) and 0.1 ml of HMDS and 0.03 ml of TMCS are added to this solution. After standing for 10 min at room temperature an aliquot of the reaction mixture is injected directly. The method was applied to the determination of faecal bile acids in the rat. Other workers [320] investigated the retention behaviour of 52 persilylated methyl esters of urine acids on QF-1, OV-1 and OV-17 stationary phases. They correlated the data expressed as relative retention times with the structures of the compounds. 

In addition to the anion exchangers, cation-exchange resins can also be usefully employed in bile acid work. Thus columns of a strong cation-exchange resin (Dowex-50, 2% cross-linked, 50-100 mesh, J.T. Baker Chemical Co.) have been used in the hydrogen form to purify extracts of bile acids prepared from biological materials (2, 30). Prior to use the resin is extracted... 

CJH4O5, H02CCH(0H)C02H. Colourless crystals with IH O lost at 60 C. M.p. IhO C (decomp.). Prepared by heating dinitrotartaric acid in aqueous alcohol, taurine, aminoethylsulpbonic acid, C2H7NO3S, NHj CHj CH SOjH. Crystallizes in columns, decomposing at 317 C. In combination with cholic acid it forms one of the bile acids. It is formed in the liver from cysteine. 

Additional applications are exemplified by the well-known Meystre-Miescher degradation of the bile acid side chain and, more recently, in the preparation of a-pyrones from a,iS-unsaturated lactones. ... 

The first studies of specificity were carried out using cholate, the glycine and taurine conjugates and taurine conjugates of the dihydroxy bile acids cheno-deoxycholate and ursodeoxycholate. Kramer and colleagues prepared plasma membrane vesicles from rat liver and compared bile-acid transport with values from CHO cells stably expressing NTCP. This work established that transport by the liver enzyme was maximal when 2 hydroxyls were present,... 

LIVER Use of isolated perfused liver in studies of biological transport processes, 192, 485 measurement of unidirectional calcium ion fluxes in liver, 192, 495 preparation and specific applications of isolated hepatocyte couplets, 192, 501 characterizing mechanisms of hepatic bile acid transport utilizing isolated membrane vesicles, 192, 517 preparation of basolateral (sinusoidal) and canalicular plasma membrane vesicles for the study of hepatic transport processes, 192, 534. 

Zhou, K., Xia, W., Zhang, C, and Yu, L. (2006). In vitro binding of bile acids and triglycerides by selected chitosan preparations and their physicochemical properties. LWT Food Sci. Technol. 39,1087-1092. 

Saponins appear to lower plasma LDL cholesterol concentration by interfering with cholesterol absorption. Studies in rats and monkeys fed naturally occurring saponins exhibited significant reductions in cholesterol absorption efficiency and an increase in fecal cholesterol excretion (Malinow et al., 1981 Nakamura et al., 1999 Sidhu et al., 1987). Decreased bile acid absorption and increased excretion has also been reported in animals fed saponins (Malinow et al., 1981 Nakamura et al., 1999 Stark and Madar, 1993). One possible mechanism of action for decreased cholesterol absorption is the ability of saponins to form insoluble complexes with cholesterol (Gestetner et al., 1972 Malinow et al., 1977). In an effort to isolate the specific properties of saponins, Malinow (1985) prepared a variety of synthetic saponins in which the complex carbohydrate moieties of native plant saponins were replaced with simplified carbohydrates such as glucose or cellobiose. One of these synthetic saponins, tiqueside (Pfizer, Inc.), can effectively precipitate cholesterol from micelle solutions in vitro and inhibit cholesterol absorption in a variety of animals (Harwood et al., 1993) and in humans (Harris et al., 1997). But despite ample data showing the formation of a saponin/cholesterol complex in vitro, there is essentially no definitive evidence that complexation occurs in the intestinal lumen (Morehouse et al., 1999). 

Several prominent types of host molecule, such as the steroidal bile acids and the cyclodextrins, are chiral natural products that are available as pure enantiomers. Chemical modification of these parent compounds provides an easy route to the preparation of large numbers of further homochiral substances. Since all these materials are present as one pure enantiomer, it automatically follows that their crystalline inclusion compounds must have chiral lattice structures. It is not currently possible to investigate racemic versions of these compounds, but the examples discussed previously in this chapter indicate that very different behaviour could result. 

S. Scalia and D.E. Games, Determination of free bile acids in pharmaceutical preparation by packed column supercritical fluid chromatography, J. Pharm. Sci., 82 44 (1993). 

Separations of complex steroid mixtures were achieved recently by Que et al. [76] using both isocratic and gradient elution. Mass spectrometric detection gave femto-mole detection limits while laser-induced fluorescence of dansylated ketosteroids ranged in attomole levels (Fig. 10.16). Monolithic column packings were used with a 35 cm (25 cm packed bed) x 100 pm i.d. capillary packed with a polymer prepared from 5% T (total monomer concentration), 60% C (total crosslinker concentration), 3% polyethylene glycol, 10% vinylsulfonic acid and 15% lauryl acrylate. Details of the monolithic column preparation can be found in refs. 36,76, and 193. Similar monolithic columns can be used for the separation of bile acids [194],... 

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