Solid oral preparation containing a pyrrolidine derivative with

Details Solid oral preparation containing a pyrrolidine derivative with Solid oral preparation containing a pyrrolidine derivative with

1991-11-26

1994-03-08

Page, Thurman K.

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Matrices

514424, 514426, 514429, 424464, 424451, 424489, A61K 31395, A61K 3140

Patent

active

052925218

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to a solid oral preparation containing a catechol compound or a pharmacologically acceptable salt thereof. In particular, the present invention relates to the preparation having an improved absorbability.


PRIOR ART

The term "catechol compound and pharmacologically acceptable salt thereof" as used in the present invention (hereinafter referred to as the compounds of the present invention) include compounds each having a catechol group of the following formula (IV) or a catechol ring of the following formula (V) in the molecule: ##STR2## wherein two OH groups are at the positions ortho to each other.
Examples of the catechol compounds include pyrrolidine derivatives of the following general formula (I) and compounds of the following formulae (II) and (III): ##STR3## wherein X represents a hydrogen atom, a halogen atom or a lower alkyl group, Y represents a group of the formula: --(CH.sub.2).sub.n -- in which n is zero or an integer of 1 or 2, a group of the formula: ##STR4## in which p is zero or an integer of 1 or 2, a group of the formula: --O-- or a group of the formula: --NH--, and R represents a substituted or unsubstituted phenyl group or a substituted or unsubstituted naphthyl group or a heteroaryl group. ##STR5##
The compounds of the present invention have a dopamine effect and are expected to be usable as a drug, i.e. a hypotensive having an effect of accelerating the renal blood circulation. A patent application on the compounds of the above general formula (I) and the use thereof as the drug have already been filed (Japanese Patent Laid-Open No. 254349/1989).
When the compound of the present invention is orally administered, the migration thereof into the circulating blood is only slight. For example, the bioavailability thereof used in an amount of around an efficacious amount is only 4 to 5% when it is given to beagles by oral administration as will be shown in the following experimental examples. Although the reasons therefor have not been fully elucidated, it is conceivable that since this compound has a catechol group or a catechol ring in its structure, it is easily subjected to conjugation and is apt to experience the first-pass effect at the absorption site and that in a neutral to alkaline zone, it is chemically unstable and, therefore, it is inclined to be subjected to an oxidative destruction in the intestinal tract as the absorption site.


DISCLOSURE OF THE INVENTION

After intensive investigations made for the purpose of improving the bioavailability of the compounds of the present invention under the above-described circumstances, the inventors have found that surprisingly the object of the invention can be attained by incorporating at least one compound selected from the group consisting of organic acids and salts thereof. The present invention has been completed on the basis of this finding.
Thus the present invention provides a solid oral preparation containing a catechol compound(s), comprising at least one compound selected from the group consisting of organic acids and salts thereof.
A detailed description will now be made on the present invention.
The compounds of the present invention are catechol compounds, i.e. compounds having a catechol group of the following formula (IV) or a catechol ring of the following formula (V) in the molecule: ##STR6## wherein the two OH groups are at the positions ortho to each other.
Examples of these catechol compounds include pyrrolidine derivatives of the above general formula (I) and pharmacologically acceptable salts thereof.
The substituted or unsubstituted phenyl groups represented by R in the general formula (I) are those of the following formula (VI): ##STR7## wherein R.sup.1, R.sup.2 and R.sup.3 may be the same or different from one another and each represent a hydrogen atom, a lower alkyl group, a lower alkoxy group, a halogen atom, a hydroxyl group, a trifluoromethyl group or group of the formula: ##STR8## and R.sup.5 being the same or different from each other and each being

REFERENCES:
patent: 4732892 (1988-03-01), Sarpotdar et al.

Affiliated with

Also associated with

Rating

Solid oral preparation containing a pyrrolidine derivative with does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Solid oral preparation containing a pyrrolidine derivative with , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Solid oral preparation containing a pyrrolidine derivative with will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-151639