Sodium ursodeoxycholate

The enhancement of nasal absorption of insulin by hydrophobic bile salts has also been investigated. It was found that minor differences in the number, position, and orientation of the nuclear hydroxyl groups as well as alterations to side-chain conjugation can improve the adjuvant potency of bile salts. Moreover, the absorption of insulin positively correlated with an increase in the hydrophilicity of the steroid nucleus of the bile salts. In the presence of bile salts, nasal absorption of insulin reached peak levels within about lOmin, and some 10-20% of the dose was found to have been absorbed into the circulation. Marked increases in serum insulin levels were seen with sodium deoxycholate, the most lipophilic of the bile salts, whereas the least elevation—as well as least lowering of blood glucose levels—was seen with the most hydrophobic bile salt, sodium ursodeoxycholate [63],... 

Abbreviations OG, n-octyl- 3-D-glucopyranoside DM, dodecylmaltoside LM, w-lauryl-( -D-glucopyranoside Azone, 1-dodecyl azacyclohepatan-2-one, SCG, sodium glycocholate STDHF, sodium tauro-2425 dihydrofusidate UCDA, ursodeoxycholate CDCA, chenodeoxycholate SDS, sodium dodecylsulfate DMSO, dimethyl sulfoxide DMF, AV-dimethyl formamide DMAC, A At-dimethyl acetamide. 

Roe, J. M., and B. W. Barry. 1982. Micellar properties of sodium salts of ursodeoxycholic chenodeoxycholic, deoxycholic and cholic acidd. Pharm. PharmacoB4 (Suppl.) 24-25. 

Because the equilibrium between the active lactone form and the ring-opened carboxylate form is pH dependent, oral alkalinization with a mixture consisting of sodium bicarbonate (2.0 g/day), magnesium oxide (2.0-4.0 g/day), water (pH over 7.2, 1.5-2 1/day), and ursodeoxycholic acid (300 mg/day), combined with controlled defecation was used in a phase II trial to reduce subacute gastrointestinal toxicity. Anticancer activity was maintained and the incidences of diarrhea and myelosuppression were significantly reduced compared with a non-randomized control group (109-111). 

Ursodeoxycholic acid was detected very early by Hammarsten in polar bear bile (85). It was isolated in crystalline form by Shoda (58) and characterized later by Iwasaki (84). The acid, which is the 7/3-epimer of chenodeoxycholic acid, may be prepared in good yield from 7-ketolithocholic acid by reduction with sodium in propanol according to Kanazawa et al. (86). Ursodeoxycholic acid was originally considered to be a unique constituent of bear bile but has since been detected as a minor constituent in the bile of several mammals including man (2). It is also present in human feces (52). 

Figure 8 A pharmacophore for the human hepatic sodium-dependent bile acid transporter using eight molecules and IC50 values demonstrating two hydrophobic features (bottom right) and two hydrogen-bond donors (top left and top right). The observed versus predicted data resulted in a correlation r = 0.97. A training set member (ursodeoxycholic acid) is shown fitted to this pharmacophore.

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