Title: Use of panaverium bromide for preventing cell
proliferation and diseases caused thereby in the liver and digestive tract
United States Patent: 6,500,826
Issued: December 31, 2002
Inventors: Christen; Marie-Odile (Paris Cedex, FR); Maugard;
Joelle (Marly le Roi, FR); Duc; Huynh (Villejuif, FR); Scherubl; Hans
(Berlin, DE); Huizinga; Jan (Ontario, CA); Blennerhasset; Michael G.
Assignee: Solvay Pharma (Suresnes, FR)
Appl. No.: 180305
Filed: April 26, 1999
PCT Filed: November 13, 1997
PCT NO: PCT/FR97/00809
371 Date: May 6, 1997
The use of panaverium bromide for treating or preventing diseases of the
liver and digestive tract caused by excessive cell proliferation therein, is
Description of the Invention
The present invention relates to a novel use of pinaverium bromide in
gastrointestinal pathologies, inflammatory digestive diseases (IBD), colites,
ulcers, Crohn's disease or functional colopathies (IBS), during which
proliferative phenomena which lead to pathological complications appear.
While the constant and rapid renewal of the epithelium of the digestive
tract is an important factor in the maintenance of the integrity of the
mucous membrane, it is also an important factor in the development of
tumours and hypertrophies.
In these latter cases, an abnormal proliferation of the epithelial cells and
an increased number of proliferative zones are always observed; this is also
found in patients who are at familial risk of cancer of the colon or in
patients who are suffering from diseases which predispose to cancer of the
digestive tract (chronic gastrites, inflammatory digestive diseases, Crohn's
disease, ulcerative colites, colonic polyps, etc.). Furthermore, it has been
shown that inflammation of the intestine can give rise to hypertrophy and
hyperplasia of the smooth muscle cells at one and the same time. This
results in a thickening of the muscle wall, and therefore in a change in its
motility, resulting in the appearance of complications which require
In addition, inhibition of the proliferation of neoplastic cells is a
determining factor in the prevention and treatment of cancers and metastases
of the digestive tract.
Pinaverium bromide is the only calcium antagonist which is selective for the
intestinal tract and which has spasmolytic activity and which is prescribed
for the chronic treatment of functional digestive disorders (irritable bowel
syndrome or IBS). This compound has been described, in particular, in French
patent 2 097 032.
The authors of the present invention have now surprisingly demonstrated, by
means of studies carried out in vitro, that pinaverium bromide is able to
inhibit the proliferation of neoplastic and hyperplastic cells of the
digestive tract, with this inhibition being greater than that brought about
by another calcium antagonist, i.e. verapamil. Furthermore, a study carried
out in vivo also demonstrated the efficacy of pinaverium bromide in
decreasing tumours induced in animals.
Pinaverium bromide can therefore be used as a medicament for preventing
cancer of the digestive tract both in the healthy individual and the
individual suffering from a digestive pathology such as IBS. In the latter
individual, it will then exert a prophylactic or therapeutic effect which
complements its effect on the IBS.
This compound may also be used for the therapeutic treatment of
hepatocarcinoma or of cancer of the pancreas and, more generally, of any
cancer of the hepatodigestive tract.
The present invention therefore relates to the use of pinaverium bromide for
preparing a medicament which is intended for preventing or treating diseases
of the hepatodigestive tract which are due to excessive proliferation of the
cells of the tract.
More especially, the invention relates to the use of pinaverium bromide for
preparing a medicament which is intended for preventing or treating
intestinal cellular hyperplasias which are linked to inflammatory digestive
diseases, or for preventing hypertrophies of the smooth-muscle-cell wall of
the intestinal tract and motor disturbances which are due to the
inflammatory diseases of the digestive tract (inflammatory bowel disease or
IBD, Crohn's disease or ulcerative colitis) which are characteristic of the
The invention is also directed towards using pinaverium bromide for
preparing a medicament which is intended for preventing or treating a cancer
of the hepatodigestive tract, comprising cancer of the colon and of the
stomach, hepatocarcinoma and cancer of the pancreas, or else the carcinoid
syndrome or functional diseases which are linked to the carcinoid tumours.
It also relates to the use of pinaverium bromide for preparing a medicament
which is intended for preventing and treating cancer of the hepatodigestive
tract in patients who are suffering from irritable syndromes of the colon
(irritable bowel syndrome or IBS), while effecting a complementary and
simultaneous treatment of the symptoms which are characteristic of the TBS.
The invention also comprises a method for the prophylactic or therapeutic
treatment of diseases of the hepatodigestive tract which are due to
excessive proliferation of the cells of the tract, which method consists in
administering a medicament containing pinaverium bromide, as the active
principle, to a patient.
Finally, the method is directed towards using pinaverium bromide for
producing a medicament which is intended for treating inflammatory digestive
diseases such as IBD (inflammatory intestinal disease or inflammatory bowel
disease), Crohn's disease or ulcerative colitis, which diseases are
generally associated with the thickening of the mucous membrane.
Preferably, within the context of the present invention, the pinaverium
bromide is used by being administered in a daily quantity of between 50 mg
and 450 mg. Administration is by the oral route or by the injectable route,
using a solution which is dosed at from 0.2 to 1 mg/ml.
Claim 1 of 14 Claims
What is claimed is:
1. A method for inhibiting hyperproliferation of hepatodigestive tract cells
connected with diseases of the hepatodigestive tract which affect the
stomach, the intestines, the colon and the liver, comprising administering
to a person suffering from or subject to a disease associated with said
hyperproliferation a pharmaceutically effective amount of pinaverium
bromide, said amount being effective to inhibit said hyperproliferation.
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