Details for Patent: 6,414,016
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Title: | Anti-constipation composition |
Abstract: | An object of the present invention is to provide an anti-constipation composition containing a halogenated-bi-cyclic compound as an active ingredient in a ratio of bi-cyclic/mono-cyclic structure of at least 1:1. The halogenated-bi-cyclic compound is represented by Formula (I): ##STR1## where X.sub.1 and X.sub.2 are preferably both fluorine atoms. The composition can be used to treat constipation without substantive side-effects, such as stomachache. |
Inventor(s): | Ueno; Ryuji (Potomac, MD) |
Assignee: | Sucampo, A.G. (Zurich, GH) |
Filing Date: | Sep 05, 2000 |
Application Number: | 09/655,760 |
Claims: | 1. A method for relieving or preventing constipation in a human constipated patient or cleansing a bowel of a patient which comprises administering to the patient a therapeutically effective amount of the pharmaceutical composition comprising in an amount sufficient for relieving or preventing constipation in a human constipated patient or cleansing a bowel of a human patient a bi-cyclic compound represented by formula (I): ##STR28## where V.sub.1 and V.sub.2 are carbon atoms; W.sub.1 and W.sub.2 are ##STR29## R.sub.3 and R.sub.4 are hydrogen atoms or one of them is OH; X.sub.1 and X.sub.2 are hydrogen, lower alkyl or halogen atom, and at least one of these is a halogen atom; Z is an oxygen atom; R.sub.2 is a hydrogen atom or alkyl; Y is a saturated or unsaturated C.sub.2-10 hydrocarbon chain which is unsubstituted or substituted by oxo, halogen, an alkyl group, hydroxyl or aryl; A is -CH.sub.2 OH, -COCH.sub.2 OH, -COOH or its functional derivative; and R.sub.1 is a saturated or unsaturated, lower hydrocarbon forming a straight-chain, a branched-chain or a ring, which is unsubstituted or substituted by halogen, oxo, hydroxy, lower alkoxy, lower alkanoyloxy, lower cycloalkyl, lower cycloalkyloxy, aryl, or aryloxy; lower cycloalkyl; lower cycloalkyloxy; aryl or aryloxy, a bond between C-13 and C-14 position can be a double or single bond, and C-15 can have a steric configuration of R, S, or a mixture thereof, and a compound which is a mono-cyclic tautomer of formula (I), wherein in the composition a ratio of the bi-cyclic compound to the mono-cyclic tautomer is at least 1:1. 2. A method for relieving or preventing constipation in a human constipated patient or cleansing a bowel of a patient which comprises administering to the patient a therapeutically effective amount of the pharmaceutical composition comprising a bi-cyclic compound represented by the following Formula (I); ##STR30## where V.sub.1 and V.sub.2 are carbon atoms; W.sub.1 and W.sub.2 are ##STR31## R.sub.3 and R.sub.4 are hydrogen atoms or one of them is OH; X.sub.1 and X.sub.2 are hydrogen, lower alkyl or halogen atom, and at least one of these is a halogen atom; Z is an oxygen atom; R.sub.2 is a hydrogen atom or alkyl; Y is a saturated or unsaturated C.sub.2-10 hydrocarbon chain which is unsubstituted or substituted by oxo, halogen, an alkyl group, hydroxyl or aryl; A is -CH.sub.2 OH, -COCH.sub.2 OH, -COOH or its functional derivative; and R.sub.1 is a saturated or unsaturated, lower hydrocarbon forming a straight-chain, a branched-chain or a ring, which is unsubstituted or substituted by halogen, oxo, hydroxy, lower alkoxy, lower alkanoyloxy, lower cycloalkyl, lower cycloalkyloxy, aryl, or aryloxy; lower cycloalkyl; lower cycloalkyloxy; aryl or aryloxy, a bond between C-13 and C-14 position can be a double or single bond, C-15 can have a steric configuration of R, S, or a mixture thereof, a compound which is a mono-cyclic tautomer of formula (I); and a medium chain fatty acid triglyceride, wherein in the composition a ratio of the bi-cyclic compound to the monocyclic tautomer is at least 1:1. 3. The method according to claim 1, wherein in the composition a ratio of bi-cyclic/mono-cyclic structure is at least 20:1. 4. The method according to claim 1, wherein A is -COOH, W.sub.1 is a ketone, R.sub.2 is a hydrogen atom, and X.sub.1 and X.sub.2 are fluorine atoms. 5. The method according to claim 1, wherein A is COOH; Y is (CH.sub.2).sub.6 ; W.sub.1 is .dbd.O; R.sub.3 and R.sub.4 are hydrogen atoms; X.sub.1 and X.sub.2 are fluorine atoms; and R.sub.1 is (CH.sub.2).sub.3 CH.sub.3. 6. The method according to claims 2, wherein the ratio of bi-cyclic/mono-cyclic structure is at least 20:1. 7. The method according to claim 2, wherein A is -COOH, W.sub.1 is a ketone, and X.sub.1 and X.sub.2 are fluorine atoms. 8. The method according to claim 2, wherein A is COOH; Y is (CH.sub.2).sub.6 ; W.sub.1 is .dbd.O; R.sub.3 and R.sub.4 are hydrogen atoms; X.sub.1 and X.sub.2 are fluorine atoms; and R.sub.1 is (CH.sub.2).sub.3 CH.sub.3. 9. The method according to claim 2, wherein the medium chain fatty acid triglyceride is present in an amount of 1-1,000,000 parts by weight based on one part by weight of the bi-cyclic structure. 10. The method according to claim 9, wherein the medium chain fatty acid triglyceride is present in an amount of 5-500,000 parts by weight based on one part by weight of the bi-cyclic structure. 11. The method according to claim 9, wherein the medium chain fatty acid triglyceride is present in an amount of 10-200,000 parts by weight based on one part by weight of the bi-cyclic structure. 12. The method according to claim 2, wherein the medium chain fatty acid triglyceride is a triglyceride of a fatty acid having 6-14 carbon atoms. 13. The method according to claim 2, wherein the medium chain fatty acid triglyceride is caprylic acid triglyceride and/or capric triglyceride. |