Absorption-promoting compounds, compositions thereof with pharmaceuticals and/or bases for rectal administration and method of use

A combination of (I) a physiologically-acceptable pharmacologically-active substance, which is rectally unabsorbable into the bloodstream or rectally absorbable into the bloodstream to an inadequate degree or only with difficulty, with (II) at least one physiologically-acceptable compound which is one of the formula ##STR11## wherein R.sup.12 is a hydrogen atom (--H) or alkyl;

• R.sup.13 is alkyl, optionally-substituted aralkyl or optionally-substituted aryl, any optional substituent being hydroxyl, alkyl or alkoxy;
• and
• R.sup.14 is alkylene or alkenylene having at least 2 carbon atoms or a group of the formula ##STR12## wherein n is 0, 1 or 2, and the phenylene ring is optionally substituted by at least one substituent selected from the group consisting of hydroxyl, alkyl and alkoxy,
• and which:
• (A) has a log P value in the range of from 2.5 to 6,
• (B) has at least one carboxyl group in its molecular structure
• (C) has a carboxyl-group pKa value of at least 2.5, and
• (D) is free from halogen atoms,
• or a nontoxic salt thereof;
• the amount of (II) being sufficient to promote absorption of (I) from the rectum into the bloodstream.

A base suitable for rectal administration of a pharmacologically-active substance and having incorporated therein at least one physiologically-acceptable compound which is an N-acylamino acid having at least 9 carbon atoms, the acyl moiety having from 2 to 18 carbon atoms, and which:

• (A) has a log P value in the range of from 2.5 to 6,
• (B) has at least one carboxyl group in its molecular structure,
• (C) has a carboxyl-group pKa value of at least 2.5, and
• (D) is free from halogen atoms,
• or a nontoxic salt thereof;
• the amount of the compound being sufficient to promote absorption of the pharmacologically-active substance from the rectum into the bloodstream.

A base suitable for rectal administration of a pharmacologically-active substance and having incorporated therein at least one physiologically-acceptable compound which is one of the formula ##STR14## wherein R.sup.12 is a hydrogen atom (--H) or alkyl;

• R.sup.13 is alkyl, optionally-substituted aralkyl or optionally-substituted aryl, any optional substituent being hydroxyl, alkyl or alkoxy;
• and
• R.sup.14 is alkylene or alkenylene having at least 2 carbon atoms or a group of the formula ##STR15## wherein n is 0, 1 or 2, and the phenylene ring is optionally substituted by at least one substituent selected from the group consisting of hydroxyl, alkyl and alkoxy, and
• which:
• (A) has a log P value in the range of from 2.5 to 6,
• (B) has at least one carboxyl group in its molecular structure,
• (C) has a carboxyl-group pKa value of at least 2.5, and
• (D) is free from halogen atoms,
• or a nontoxic salt thereof;
• the amount of the compound being sufficient to promote absorption of the pharmacologically-active substance from the rectum into the bloodstream.

A method of promoting absorption of a pharmacologically-active substance through the rectum into the bloodstream of a mammal which comprises rectally administering the pharmacologically-active substance to the mammal together with at least one physiologically-acceptable compound which is an N-acylamino acid having at least 9 carbon atoms, the acyl moiety having from 2 to 18 carbon atoms, and which:

• (A) has a log P value in the range of from 2.5 to 6,
• (B) has at least one carboxyl group in its molecular structure,
• (C) has a carboxyl-group pKa value of at least 2.5, and
• (D) is free from halogen atoms,
• or a nontoxic salt thereof;
• the amount of the compound being sufficient to promote absorption of the pharmacologically-active substance from the rectum into the bloodstream.

A method of promoting absorption of a pharmacologically-active substance through the rectum into the bloodstream of a mammal which comprises rectally administering the pharmacologically-active substance to the mammal together with at least one physiologically-acceptable compound which is one of the formula ##STR17## wherein R.sup.12 is a hydrogen atom (--H) or alkyl;

• R.sup.13 is alkyl, optionally-substituted aralkyl or optionally-substituted aryl, any optional substituent being hydroxyl, alkyl or alkoxy;
• and
• R.sup.14 is alkylene or alkenylene having at least 2 carbon atoms or a group of the formula ##STR18## wherein n is 0, 1 or 2, and the phenylene ring is optionally substituted by at least one substituent selected from the group consisting of hydroxyl, alkyl and alkoxy, and which:
• (A) has a log P value in the range of from 2.5 to 6,
• (B) has at least one carboxyl group in its molecular structure,
• (C) has a carboxyl-group pKa value of at least 2.5, and
• (D) is free from halogen atoms,
• or a nontoxic salt thereof;
• the amount of the compound being sufficient to promote absorption of the pharmacologically-active substance from the rectum into the bloodstream.