5-aminosalicylate degradation

The degradation of salicylate to catechol is initiated by monooxygenation accompanied by decarboxylation (salicylate-l-hydroxylase), and two different and independent salicylate hydroxylases have been found in the naphthalene-degrading Pseudomonas stutzeri ANIO (Bosch et al. 1999). Alternatively, in Rhodococcus sp. strain B4, salicylate is hydroxylated to 2,5-dihydroxybenzoate by salicylate-5-hydroxylase (Grand et al. 1992). An alternative occurs for 5-hydroxy- and 5-aminosalicylate in Pseudaminobacter salicylatoxidans in which ring fission is accomplished directly (Hintner et al. 2001). 

An analogous pathway is used for the degradation of 5-aminosalicylate that is an intermediate in the degradation of 6-aminonaphthalene-2-sulfonate. Direct ring fission of both 5-aminosalicylate and 5-hydroxysalicylate can be accomplished by a salicylate 1,2-dioxygenase in Pseudaminobacter salicylatoxidans (Hintner et al. 2001). 

Aromatic azo compounds, many of which are sulfonated, are components of many commercially important dyes, colorants, and pigments, so that attention has been directed to their degradation and transformation. These compounds are often considered recalcitrant, although then-transformation has been accomplished by reduction to amines with scission of the Ar-N=N-Ar bond to produce arylamines. The amines may then be degraded, for example, 6-aminonaphthalene-2-sulfonate by dioxygenation and ring fission to 5-aminosalicylate (Hang et al. 1991). This is then... 

The prototypical aminosalicylate is sulfasalazine, which is comprised of mesalamine linked by a diazo bond to the carrier molecule sulfapyridine. This linkage prevents premature absorption of mesalamine in the small intestine. Once sulfasalazine is delivered to the colon, bacterial degradation of... 

Ueda, T., Yamaoki, T., Miyamoto, M., Kimura, Y., Sasatani, H., and Kim, S.I., Baeterial reduction of azo compounds as a model reaction for the degradation of azo-eontaining polyurethane by the action of intestinal flora. Bull Chem. Soc. Jpn., 69 1139-1142 (1996). Krishnaiah, Y.S., Satyanarayana, S., and Prasad, Y.V., Studies of guar gum eompression-coated 5-aminosalicylic acid tablets for colon-specific drug delivery. Drug-Dev. Ind. Pharm., 25 651-657 (1999). 

This drug possesses antibacterial activity with respect to a few cocci and colon bacillus. It exhibits a simultaneous, pronounced healing effect in patients with nonspecific ulcerative colitis, which is explained by the degradation in the body of 5-aminosalicylic acid and sulfapyridine, which possess anti-inflammatory and antibacterial properties. It is used for ulcerative colitis, chronic rhenmatoid arthritis as well as acnte and snbacnte inflammatory diseases. Synonyms of this drng are slazopyrin, salazosnlfapyridine, and others. 

Literature on pharmaceutical sciences is replete with oxidative degradation of drugs in solution. 5-Aminosalicylic acid undergoes oxidation and the product of oxidation forms polymeric compounds [28]. Further, morphine has been reported to be oxidatively degraded in solution [29] as well as hydrocortisone [30]. 

Jensen, J, Cornett, C, Olsen, C. E.,Tjornelund, I, and Hansen, S. H. (1992), Identification of major degradation products of 5-aminosalicylic acid form in aqueous solutions and in pharmaceuticals, Int. J. Pharm., 88,177-187. 

Alternatively, the enzyme in the gut can be utilized to control the release of the active drug in the gut. For example, sulfasalazine, which is employed in the treatment of ulcerative colitis, is a combination of sul-fapyridine and 5-aminosalicylate chemically linked via an azo bond. It remains absorbed and intact throughout the GI tract until it reaches the large intestine, where bacterial azoreductase enzymes degrade the azo bond and release sulfapyridine and 5-aminosalicylate to act locally on the lesions. 

Figure 4.6 Degradation of powdered p-aminosalicylic acid in a dry atmosphere at elevated temperatures.

Elimination degradation pathways are also possible. Decarboxylation, in which a carboxylic acid releases a molecule of CO2, occurs for p-aminosalicylic acid.24 Oxidation is very common as well, largely due to the presence of oxygen during manufacture and/or storage. Several examples can be found in Yoshioka and Stella.14 Isomerization and racemization reactions are other degradation pathways. Two compounds which undergo isomerization reactions are amphotericin B25 and tirilizad.26... 

The release of 5-aminosalicylic acid from tablets coated with (i-CD was investigated in a colonic environment using the colonic microflora test [78], Bisoprolol was also released by colonic bacteria like Proteus mirahilis and Escherichia fergu-sonii, after incubating with (i-CD coated tablets. Eudragit RS films with incorporated inulin also were described for their successful degradation in human fecal medium [79]. 

Oxidation mechanisms for drug substances depend on the chemical structure of the drug and the presence of reactive oxygen species or other oxidants. Catechols such as methyl-dopa180 and epinephrine181 are readily oxidized to quinones, as shown in Scheme 45. 5-Aminosalicylic acid undergoes oxidation and forms quinoneimine,182 which is further degraded to polymeric compounds (Scheme 46).183 Ethanolamines such as procaterol are oxidized to formyl compounds (Scheme 47),184 whereas thiols such as 6-mercaptopurine,185... 

Oxidative degradation of solid sulpyrine in the presence of moisture was described by Eq. (2.68).289 This equation was also used to describe decarboxylation of 4-aminosalicylic... 

Sulfasalazine is degraded by intestinal flora to sulfapyridine and 5-aminosalicylate (me-salamine). Release of high concentrations of salicylate in the colon exerts anti-inflammatory action, the major benefit of the use of sulfasalazine in ulcerative colitis (and presumably rheumatoid arthritis). Mesalamine is an inhibitor of cyclooxygenases and lipoxygenases, decreasing the formation of inflammatory eicosanoids. The answer is (B). 

KGM and acrylic acid crosslinked by N,N-methylene bis-(acrylamide) 5-aminosalicylic acid Hydrogel Swelling behavior and degradation process showed that the gel was pH sensitive. Release rate of the model drug 5-ASA was proven to be controlled by swelling and degradation processes. The accumulative release percent of 5-ASA reached 95.19% after 36 h. [103]... 

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