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. (Ontario, CA)

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 disclosed.

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 surgical treatments.

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 IBS.

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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