Drug – bio-affecting and body treating compositions – Digestive system regulator containing solid synthetic...
Patent
1999-05-14
1999-12-21
Nazario-Gonzales, Porfirio
Drug, bio-affecting and body treating compositions
Digestive system regulator containing solid synthetic...
556 77, 556 79, 514503, A61K 3174, A61K 3129, C07F 994
Patent
active
060045469
DESCRIPTION:
BRIEF SUMMARY
This invention relates to an essentially water-insoluble compound of bismuth and a polyacrylic acid, use of same for treatment of conditions of the alimentary tract, particularly inflammatory bowel disease and processes for the preparation of said bismuth-polyacrylic acid compounds.
Polyacrylic acid and sodium salts thereof are disclosed in GB-A-2220855 for the treatment of inflammatory bowel disease.
Bismuth compounds are known to treat various medical disorders, such as the treatment of gastric and duodenal ulcers. More recently WO 92/01457 disclosed a bismuth-carbomer compound for the treatment of conditions of the alimentary canal particularly certain inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. Since the carbomer was mucoadhesive, it could hold the bismuth in contact with the diseased bowel wall. The bismuth content of the water-soluble compound of WO 92/01457 was reported as 8.74% w/w and 15.2% w/w (example 4).
The compounds of WO 92/01457 are formed by mixing bismuth salts and polyacrylic acid in aqueous media then neutralising the media to allow reaction. At this point the compound is present as a viscous gel which can then be used as an enema. The compound was precipitated using a water-miscible solvent such as methanol. The resulting powder, however, is difficult to formulate and gives inadequate dispersion and covering of the bowel wall. Furthermore, the process is not very economical on an industrial scale because of the difficulty in handling and separating the high viscosity gel-like compound, the low yield and the high volume of solvent used.
WO 95/20970 describes a more economical process for preparing a water-soluble compounds of bismuth and polyacrylic acid. In the improved process, polyacrylic acid is dispersed in a solution of alkali or ammonia in a water-miscible organic solvent such as methanol or ethanol, bismuth salt is added to this dispersion, and then water or a water-miscible organic solvent is added to the dispersion and the resultant medium left for several days to form a water-soluble compound of bismuth and polyacrylic acid. Finally the resulting slurry of compound is filtered, washed in aqueous ethanol, then dried to form a free-flowing powder. This powder can then be used in gelatin capsules, but like the compound of WO 92/01457 will not give an adequate covering of the bowel wall when given orally. The compounds of bismuth and polyacrylic acid of WO92/01457 and WO95/20970 are hereinafter referred to as the compounds of the prior art.
FR-A-2703250 discloses a gel-forming or dispersible dosage form consisting of a water-insoluble basic bismuth salt and gel-forming agent which is diluted with a diluent or inert vehicle. The specified gel-forming agents include polyacrylic acids and specifically certain Carbopols. Polyacrylic acid must be reacted with a base to form a gel, and accordingly an aqueous dispersion of the polyacrylic acid is added to a suspension of the bismuth salt in an aqueous solution of an amine. Other gel-forming agents disclosed are guar gum, xanthan gum and polyacrylamide, which do not have functional acid groups.
It is an object of the present invention to provide an improved compound of bismuth and polyacrylic acid over those discussed herebefore, more particularly to provide an improved dispersion in the bowel and covering of the bowel wall.
It is a further object of the invention to provide a good mucoadhesive compound of bismuth and polyacrylic acid.
We have now discovered compounds of bismuth and polyacrylic acid which are physically distinguishable from the prior art compounds discussed herebefore, and which have greatly improved physical and pharmacological properties.
Accordingly in a first aspect of the present invention there is provided an essentially water-insoluble compound of bismuth and a polyacrylic acid (hereinafter referred to as compounds of the invention).
By essentially insoluble we mean having a solubility of no more than about 0.5 gl.sup.-1, preferably no more than about 0.1 gl.sup.-1, most preferably
REFERENCES:
patent: 5601848 (1997-02-01), Marshall
Medeva Europe Limited
Nazario-Gonzales Porfirio
LandOfFree
Pharmaceutical composition containing bismuth-polyacrylic acid c does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutical composition containing bismuth-polyacrylic acid c, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical composition containing bismuth-polyacrylic acid c will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-502153