PubMed · 5506949
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E Koutsoulieris, E Kaslaris. 1970. Congenital tuberculosis.. https://doi.org/10.1136/adc.45.242.584
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A novel polyanhydride, poly[(5-carboxybutyl formamide)-2-acetyl salicylic anhydride] (P(CBFAS)), with 5-aminosalicylic acid (5-ASA) incorporated into the polymer backbone was synthesized and characterized by infrared, (1)H-nuclear magnetic resonance, differential scanning calorimetry, vapor pressure osmometry, etc. The polyanhydride was subjected to degradation and simultaneously released 5-ASA and its derivative 5-acetyl aminosalicylic acid (5-acetyl ASA) in vitro under various conditions. The factors influencing the release profiles of 5-ASA and 5-acetyl ASA, including polymer molecular weights, pH value, enzyme and rat gastrointestinal contents, were examined. The results showed that the release rate of 5-ASA and 5-acetyl ASA increases with increasing pH value and with decreasing molecular weights. In PBS (pH 8.0, 37 degrees C) total ASA released was 8.0% for P(CBFAS)(1) (Mn 10770) in 13 h, but only 1.1 and 2.6% at pH 2.0 and 6.5, respectively. Enzymes including pepsin and trypsin, as well as rat gastric and jejunum contents had little effect on the release rate of 5-ASA and 5-acetyl ASA at pH 2.0 and 6.5 (less than 4% in 13 h). However, the release rate of 5-ASA and 5-acetyl ASA was much fast in PBS(pH 8.0) containing 5% of cecal contents, the total ASA released was 13.6% for the polymer in 13 h. Considering the high drug loading of the polymer (50.2% of 5-ASA moieties in the backbones) and the degradation characters, it is possible to reach high local concentration of 5-ASA in the colon site via oral administration. Therefore, P(CBFAS) may be potentially useful in the colon specific delivery of 5-ASA.
Nitric oxide can accelerate ulcer healing and exert anti-inflammatory effects. Addition of a nitric oxide-releasing moiety to mesalamine significantly boosts its anti-inflammatory activity. NO-releasing mesalamine suppresses inflammatory cytokine production and reduces leukocyte infiltration.
The chemoprevention of colorectal cancer (CRC) with long-term sulfasalazine and 5-aminosalicyclic acid (5-ASA) treatment has been demonstrated through epidemiological and experimental studies, in patients with ulcerative colitis. In a large case-controlled study, there was a trend for long-term nonsteroidal anti-inflammatory consumption to be protective against CRC in patients with inflammatory bowel disease (IBD) (OR, 0.84). Sulfasalazine treatment over a 3-month period was shown to be protective (OR, 0.38), independently of disease activity. A longer-term study of sulfasalazine also revealed a relationship with treatment compliance, where 3% of compliant patients developed CRC compared with 31% of the noncompliers. Treatment with 5-ASA was associated with an increase in apoptosis, a decrease in proliferation of colorectal mucosa and has been shown to lower the rate of spontaneous mutation. In a retrospective, matched case-control study conducted in the UK, 102 patients with ulcerative colitis and CRC were matched with ulcerative colitis patients without CRC. Incidence was correlated to treatment protocols, family history and other risk factors. Mesalazine was the only treatment to be associated with a statistically significant reduction in the risk of developing cancer. Even after adjusting for variables, mesalazine at doses > 1.2 g / day reduced the risk of cancer by 81% (P = 0.006). Frequent visits to the clinician were also associated with a protective effect.