Remedy for pancreatitis

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

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544204, A61K 3153

Patent

active

058859934

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to a remedy for pancreatitis.


BACKGROUND ART

Pancreatitis is classified mainly into acute pancreatitis caused by autodigestion due to intracellular activation of the digestive enzymes produced in the exocrine pancreas and chronic pancreatitis which, by fibrosis, progresses to irreversible functional failure of the pancreas. The etiology of pancreatitis remains to be fully elucidated as yet. The therapeutic approach to acute pancreatitis consists of, to start with, conservative therapies such as removal of causes, pancreatic protection, arrest of pancreatic autodigestion, and removal of pain. Referring to pharmacotherapy, arrest of pancreatic autodigestion is sought by the administration of proteolytic enzyme inhibitors such as gabexate mesylate, camostat mesylate, nafamostat mesylate, urinastatin, and aprotinin. The treatment of chronic pancreatitis consists of therapies analogous to that of acute pancreatitis in relapsing episodes involving abdominal pain and prohibition of alcohol intake and restriction of fat-rich food in remissions. The protease inhibitors in use today for the pharmacotherapy of pancreatitis are only effective in relieving some of the symptoms of pancreatitis and have various side effects, thus being not clinically satisfactory enough.
Meanwhile, the list of therapeutic drugs for pancreatitis under development today includes several compounds such as loxiglumide, which is a cholecystokinin antagonist, and FK480, which is a protease inhibitor. Furthermore, it has been reported that the antiulcer compound irsogladine is structurally akin to the compound of the invention, proved efficacious in an animal model of cerulein (hereinafter referred to briefly as Cn)-induced acute pancreatitis (the Proceedings of the 36th Congress of The Japanese Society of Gastroenterology, p.266).
The inventors of the present invention discovered that the 2-amino-4-substituted amino-6-(2,5-dichlorophenyl)-1,3,5-triazine derivative according to the invention has antihepatitis activity, thus being a compound of value as a therapeutic drug for hepatitis, and already filed a patent application (WO96/04914).


DISCLOSURE OF INVENTION

In view of the retarded progress in the development of therapeutic drugs for pancreatitis, the inventors of the present invention endeavored to develop a substance having satisfactory antipancreatitis activity. The object of the invention, therefore, is to provide a therapeutic drug for pancreatitis which is more effective and less liable to elicit adverse drug reactions than the prior art therapeutic drugs for pancreatitis.
The inventors discovered that the compound of the following general formula low toxic potential and accordingly have completed the instant invention.
The present invention relates to a therapeutic composition for pancreatitis thereof, or a solvate thereof, as an active ingredient. ##STR2##
Referring to the above formula, R.sup.1 and R.sup.2 may be the same or different and each represents hydrogen, alkyl which may be substituted, aralkyl, arylalkenyl, or aryl or R.sup.1 and R.sup.2 in combination with the adjacent N atom, i.e. in the form of NR.sup.1 R.sup.2, represent a 4-through 8-membered cyclic amino group, which cyclic amino group may contain nitrogen, oxygen, or sulfur as a ring member in addition to said N atom and may also be substituted.
The present invention is predicated on the finding that said 2-amino-4-substituted amino-6-(2,5-dichlorophenyl)-1,3,5-triazine known to have antihepatitis activity is possessed of antipancreatitis activity which is quite unrelated with antihepatitis activity.
As will be set forth in the test examples presented hereinafter, the compound of the present invention has by far superior efficacy compared with irsogladine maleate model of pancreatitis which presents with a histological picture closely simulating the clinical picture of acute pancreatitis. Thus, in the rat model of pancreatitis induced by administration of cerulein (Cn), a pancreatitis-inducing chemical, plus water

REFERENCES:
Chemical Abstracts 106:95920u.
Japanese Journal of Gastroenterology vol. 91--Sep. 1994 2,4-Diamino-6-(2.5-dichlorophenyl)-s-trianzinemaleate, by Ueda et al.

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