DRUG PROFILE OF NOVAL ANTIULCER AND MUCOPROTECTIVE DRUG WITH ANTI HELICOBACTER PROPERTY: SOFALCONE
Sofalcone, 2’-carboxymethoxy-4, 4’-bis (3-methyl-2-butenyloxy) chalcone, is an anti-ulcer drug. It enhances the protective qualities of mucus component of gastric mucosal barrier and inhibits growth of Helicobacter pylori.1-3. Chalcones are obtained from natural plant sources and can also be synthesized in the laboratory. Chalcones have been reported to possess a variety of biological properties, including anti-inflammatory, analgesic, antioxidant, antibacterial, antifungal, and antiprotozoal activities. They are also reported to be gastric protectant, antimutagenic, and antitumorogenic. Sofalcone is a type of ﬂavonoid and a synthetic derivative of sophoradine which is isolated from the root of the Chinese medicinal plant Sophora subprostrata
Molecular Formula: C27H30O6
Molecular Weight: 450.53
Appearance Light yellow to yellow crystals.
Solubility Soluble in dimethylformamide and in dichloromethane. Slightly soluble in methanol.
Identification 1) Potassium permanganate test
2) Potassium iodide test
3) IR absorption spectrum
4) Absorption spectrum (l in 100,000)
Absorption 665-705 nm
Melting range 142-146 Celsius degree
Heavy metals Not more than 10ppm
Arsenic Not more than 1ppm
Related substances Not more than 0.20%
Loss on drying: Not more than 0.20%
Sulfated ash: Not more than 0.1%
Assay(HPLC): Not less than 98.5%
Sofalcone is an anti-ulcer drug. It enhances the protective qualities of mucosal component of gastric mucosal barrier and inhibits growth of helicobacter pylori.
The effect of sofalcone on gastric mucosal injury induced by ischemia-reperfusion (I-R) injury was studied in rats 5. I-R injury was produced in rat stomach by applying a small clamp to the celiac artery for 30 min and by removal of the clamp for 60 min. The increase in total area of erosions in the stomach after I-R and the increase in lipid peroxides in the gastric mucosa were significantly inhibited by intragastric administration of sofalcone. In addition, sofalcone significantly inhibited the lipid-soluble free radical initiator-induced increase in lipid peroxides of the gastric mucosal homogenate, and could show scavenging action of superoxide radicals in aprotic solvent. These results showed that the protective effect of sofalcone against I-R-induced gastric mucosal injury is attributable to its antioxidant activities in the lipophilic phase.
The effect of prolonged administration of an antiulcer drug, sofalcone, on the physicochemical properties of gastric mucus was investigated6. The experiments were conducted with two groups of rats in which one group received a dose of 100 mg/kg of sofalcone twice daily for three consecutive days, and the control group received daily doses of vehicle. The rats were killed 16 h after the last dose, their stomachs dissected, and the mucosa subjected to physicochemical measurements. The results revealed that sofalcone evoked a 23% increase in mucus gel thickness, and its content of sulfo- and sialomucins increased by 54 and 25%, respectively. These changes in mucus with sofalcone were accompanied by a 16% increase in H+ retardation capacity, twofold increase in viscosity, and a 39% increase in the gel hydrophobicity. The mucus laborated in the presence of sofalcone exhibited a 10% lower content of protein, 30% higher content of carbohydrate, and 18% higher content of total lipids, which were particularly enriched (20%) in phospholipids and contained 67% more covalently bound fatty acids. Furthermore, the high molecular weight mucus glycoprotein form accounted for about 30% of gel mucin in the control group, whereas its content in mucus gel of animals receiving sofalcone reached 50%. The results indicate that sofalcone enhances the protective qualities of the mucus component of the gastric mucosal barrier and hence strengthens the gastric mucosal integrity.
Eradication therapy for Helicobacter pylori (H. pylori) has been established8 . However, the physiological factors influencing the success of treatment remain unclear. The aim of this study was to analyze these factors and to evaluate the efficacy of sofalcone on H. pylori eradication therapy. Forty-four H. pylori-infected and peptic ulcer patients were enrolled in this study. Twenty-seven patients were treated with lansoprazole (LPZ, 30 mg o.d. for 1-8 weeks) and amoxicillin (AMPC, 500 mg q.i.d, 1-2 weeks), followed by 8 weeks of treatment with famotidine (FAM, 20 mg o.d.). Moreover, sofalcone (SOF, 100 mg t.i.d) was administered to 17 patients throughout the therapeutic period. Endoscopic and serologic evaluations and the urea breath test (UBT) were performed before therapy. At the endoscopic examination, mucosal samples were biopsied and then tissue myeloperoxidase (MPO) content, an index of neutrophil infiltration was measured. Cure of H. pylori infection was determined 8 weeks after the cessation of LPZ. This eradication regimen afforded an overall cure rate of 63.0% (17/27) without SOF and 76.5% (13/17) with SOF. In the control group, treatment success was inversely associated with pre-UBT value (gastric urease activity), whereas this association was not observed in the SOF group. Furthermore, in the patients exhibiting a high pre-UBT value (>40%), a twofold higher eradication rate was obtained by the administration of SOF. In patients who were successfully eradicated, mucosal MPO level was slightly higher than those of unsuccessful cases, whereas there was no significant association with serum pepsinogen (PG I, PG II) concentration and its ratio (PG I/PG II). These results suggest that a low UBT value is a factor predicting treatment success. SOF administration may improve the eradication rate, especially in the high-UBT sub-group.
Sofalcone has been reported to exert anti-ulcer and gastroprotective actions, but its exact mechanism of action remains unknown.So there is no report indicating the adverse reactions in literature.Sofalcone in the rat seem to stimulate autonomic nerve regeneration in acetic acid- induced ulcer from the viewpoint of synapse formation.
Sofalcone, a mucoprotective agent, increases the cure rate of Helicobacter pylori infection when combined with rabeprazole, amoxicillin and clarithromycin.
Gastric Urease activity is inversely associated with the Success of Treatment for Helicobacter pylori
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5. Suzuki, Masayuki M.D, Kitahora, Tetsuo M.D, Nagahashi, Shouichi M.D, Suzuki, Hidekazu M.D ,Mori, Mikiji M.D ,Hibi, Toshifumi M.D ,Ishii, Hiromasa M.D. journal of Clinical Gastroenterology. 27 Supplement 1:S183-S186, 1998.
8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&lis... 469&dopt=Abstract.