Drug – bio-affecting and body treating compositions – Inorganic active ingredient containing – Aluminum – calcium or magnesium element – or compound containing
Patent
1995-12-21
1998-02-10
Weddington, Kevin E.
Drug, bio-affecting and body treating compositions
Inorganic active ingredient containing
Aluminum, calcium or magnesium element, or compound containing
424683, 424684, 424686, 424688, 424690, 424693, 424717, 514 65, 514163, 514166, A61K 3306, A61K 3310, A61K 3308, A61K 3161
Patent
active
057166480
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/DK94/00223 filed Jun. 8, 1994.
FIELD OF THE INVENTION
The present invention provides compositions for oral or rectal administration having pH-regulating effect, in particular for raising a subnormal pH in the intestine to a pH close to the pH usually found in the intestine, and/or the use of a composition in the treatment of bowel diseases e.g. inflammatory bowel diseases and/or for obtaining ulcer healing in the intestine.
In particular, the composition according to the invention optionally contains an active medicament for the treatment of Crohn's disease or colitis ulcerosa, e.g. 5-aminosalicylic acid (5-ASA).
BRIEF DISCLOSURE OF THE INVENTION
In one of its broadest aspects, the invention provides a composition for oral administration, said composition comprising: within said coating, said pH regulating alkaline material being substantially insoluble (as defined herein), the nature and the amount of said coating and of said pH regulating alkaline material being adapted so as to ensure the availability of an amount of said pH regulating alkaline material in the lumen of a target part of the gastrointestinal tract from the proximal small intestine to rectum, said target part exhibiting a pH below the pH normally found in said target part, and to ensure a raise in the pH in said lumen to a pH which is close to the pH normally found in said target part.
The target part may be a part which by one or more intraluminal pH-measurements has shown pH values below the pH value normally found in said target part.
An aspect of the invention is a composition which is adapted to raise the pH to a pH within the 5-95 percentiles of the normal pH values in said target part of the gastrointestinal tract.
According to a main aspect of the invention, the target part exhibiting a pH below the pH normally found is the proximal small intestine, the mid small intestine, the distal small intestine, the caecum, the ascending colon, the transverse colon, the descending colon, the sigmoid colon and/or the rectum.
The invention provides a composition for oral administration, the composition comprising a coating which enables the pH regulating alkaline material to pass through the ventricle substantially without being affected by the gastric juices.
THE IMPORTANT ASPECTS OF THE INVENTION
The particular advantages of the composition and use according to the invention are that a specific pH adjustment which is targeted to the individual parts of the intestine has been made possible.
The localized pH adjustments according to the invention can be related to the varying pH values prevailing in the various parts of the intestines.
It has been found that in normal subjects the pH values varies considerably in different parts of the gastrointestinal tract. Fallingborg et al., (Ailment. Pharmacol. Therap. 3, 605-613 (1989)) used a pH sensitive radiotransmitting capsule for pH determinations in the intestinal lumen of various parts of the intestinal tract. The location of the capsule was determined by X-ray.
In all subjects pH values below 3 were found in the stomach. When the capsule entered the duodenum a sharp rise occurred, and the pH reached a median value of 6.4. The pH level gradually increased down the small intestine.
The median values were: 6.6 in the proximal part, 7.0 in the mid part, and 7.3 in the distal part of the small intestine. In 17 subjects pH decreased gradually by 0.1-0.8 pH units during the last hours the capsules stayed in the distal part of the small intestine, but the pH did not fall below 6.3.
When the capsule reached the caecum, the pH dropped from 0.5 to 2.5 pH units to a median value of 5.7. The pH levels of the ascending colon and the transverse colon were almost identical to that of the caecum (5,6 in the ascending and 5.7 in the transverse colon), but the pH rose in the descending colon (6,6), and in the sigmoid colon and rectum (6,6). The median faecal pH was 6.5.
The present invention relates to the adjustment of LOW pH values in the intestine, i.e. raising subnormal
REFERENCES:
patent: Re33239 (1990-06-01), Halskov
patent: 4289750 (1981-09-01), Kopp et al.
patent: 4451454 (1984-05-01), Wong
patent: 4496553 (1985-01-01), Halskov
patent: 4632921 (1986-12-01), Bauer
patent: 4744987 (1988-05-01), Mehra et al.
patent: 4980173 (1990-12-01), Halskov
patent: 5541170 (1996-07-01), Rhodes et al.
CA: 114(30125) Enteric Formulations of Physiologically-Active Peptides and
Fass (1992), Farmacevtiska specialiteter i Sverige, Fortechning over humanlakemedel, p. 622.
Fallingborg, J. et al, Aliment. Pharmacol. Therap. 3, 605-613 (1989).
United States Pharmacopoeia XXII NF XVII, 1990.
Fallingborg, J. et al, "Gastrointestinal pH-Profiles In Patients With Active Ulcerative Colitis"--Symposium IBD and Salicylates, Paris, Dec. 10-11, 1992.
Svartz, N., Acta Med. Scand. 110, 577-596 (1942).
Klotz, U., Clin. Pharmacokinet. 10, 285-302 (1985).
Hanauer, S.B., Scand. J. Gastroenterol. 25, suppl. 175, 97-106 (1990).
Lauterburg, B.H. et al, "Inflammatory Bowel Disease: Current Status and Future Approach", editor R. P. MacDermott, Elsevier Science Publisher B.V., 273-277 (1988).
Fischer-Nielsen et al, Free Radical Biology & Medicine, 13, 121-126 (1992).
Ahnfelt-R.o slashed.nne et al, Gastroenterol. 98, 1162-1169 (1990).
Palsmeier, R.T. et al, Pharm. Res. 9, 933-938 (1992).
Roediger et al, Biochem. Pharmacol. 35(2), 221-225 (1986).
Roediger et al, Pharmacology 39, 39-45 (1989).
Halskov S.o slashed.ren
Jepsen Svenn Kluver
Farmaceutisk Laboratorium Ferring A/S
Weddington Kevin E.
LandOfFree
Compositions for use in the regulation of subnormal pH values in does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compositions for use in the regulation of subnormal pH values in, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions for use in the regulation of subnormal pH values in will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2075272