Enhancement of activity and/or duration of action of soft anti-inflammatory steroids for topical or other local application
OwnerNicholas S. Bodorinventor
Life of this patent
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Abstract
Methods and compositions for enhancing the activity and/or duration of action of loteprednol etabonate and other soft anti-inflammatory steroids of the haloalkyl 17α-alkoxycarbonyloxy-11β-hydroxyandrost-4-en-3-one-17β-carboxylate type and the corresponding Δ1,4-compounds are described. The enhancing agents have the formula: wherein R is H or C1-C4 alkyl; Z1 is carbonyl or β-hydroxymethylene; X1 is —O— or —S—; R5 is —OH, —OR6, —OCOOR6 or —OCOR7 wherein R6 is C1-C4 alkyl and R7 is C1-C4 alkyl, fluoromethyl or chloromethyl; and the dotted line in ring A indicates that the 1,2-linkage is saturated or unsaturated; with the proviso that when R is C1-C4 alkyl, then R5 is —OH.
Claims26
A method for enhancing the anti-inflammatory activity or duration of action, or both, of a compound having the formula:
- wherein:
- R1 is C1-C7 alkyl;
- Z is carbonyl or β-hydroxymethylene;
- X is Cl or F;
- and the dotted line in ring A indicates that the 1,2-linkage is saturated or unsaturated;
- following topical or other local administration of said compound to a warm-blooded animal in need of treatment to alleviate a topical or other localized inflammatory response, said method comprising topically or otherwise locally co-administering said compound to said animal with a synergistically effective amount of a compound having the formula:
- wherein:
- R is H or C1-C4 alkyl;
- Z1 is carbonyl or β-hydroxymethylene;
- X1 is —O— or —S—;
- R5 is —OH, —OR6, —OCOOR6 or —OCOR7 wherein R6 is C1-C4 alkyl and R7 is C1-C4 alkyl, fluoromethyl or chloromethyl;
- and the dotted line is defined as above;
- with the proviso that when R is C1-C4 alkyl, then R5 is —OH;
- the amount of compound of formula (II) being sufficient to enhance the anti-inflammatory activity or duration of action, or both, of said compound of formula (I);
- with the proviso that [3H]-triamcinolone acetonide is excluded.
A method for enhancing the anti-inflammatory activity or duration of action, or both, of loteprednol etabonate following topical or other local administration thereof to a warm blooded animal in need of treatment to alleviate a topical or other localized inflammatory response, said method comprising topically or otherwise locally co-administering loteprednol etabonate to said animal with a synergistically effective amount of a compound having the formula:
- wherein R is H or C1-C4 alkyl and the dotted line in ring A indicates that the 1,2-linkage is saturated or unsaturated, the amount of compound of formula (IIa) being sufficient to enhance the anti-inflammatory activity or duration of action, or both, of loteprednol etabonate, with the proviso that [3H]-triamcinolone acetonide is excluded.
A method for alleviating inflammation in or on a warm-blooded animal exhibiting a topical or other localized inflammatory response, which comprises topically or otherwise locally administering to said animal an anti-inflammatory effective amount of a combination comprising:
- (a) a compound having the formula:
- wherein:
- R1 is C1-C7 alkyl;
- Z is carbonyl or β-hydroxymethylene;
- X is Cl or F;
- and the dotted line in ring A indicates that the 1,2-linkage is saturated or unsaturated;
- and
- (b) a compound having the formula:
- wherein:
- R is H or C1-C4 alkyl;
- Z1 is carbonyl or β-hydroxymethylene;
- X1 is —O— or —S—;
- R5 is —OH, —OR6, —OCOOR6 or —OCOR7 wherein R6 is C1-C4 alkyl and R7 is C1-C4 alkyl, fluoromethyl or chloromethyl;
- and the dotted line is defined as above;
- with the proviso that when R is C1-C4 alkyl, then R5 is —OH;
- in a combined synergistic anti-inflammatory effective amount;
- the amount of compound of formula (II) being sufficient to enhance the anti-inflammatory activity or duration of action, or both, of said compound of formula (I);
- with the proviso that [3H]-triamcinolone acetonide is excluded from the combination.
A method for alleviating inflammation in or on a warm-blooded animal exhibiting a topical or other localized inflammatory response, which comprises topically or otherwise locally administering to said animal an anti-inflammatory effective amount of a combination comprising loteprednol etabonate and a compound having the formula:
- wherein R is H or C1-C4 alkyl and the dotted line in ring A indicates that the 1,2-linkage is saturated or unsaturated, in a combined synergistic anti-inflammatory effective amount, the amount of the compound of formula (IIa) being sufficient to enhance the anti-inflammatory activity or duration of action, or both, of loteprednol etabonate, with the proviso that [3H]-triamcinolone acetonide is excluded from the combination.
A method for alleviating inflammation in or on a warm-blooded animal exhibiting a topical or other localized inflammatory response, which comprises topically or otherwise locally administering to said animal an anti-inflammatory effective amount of a pharmaceutical composition comprising:
- (1) a combined synergistic anti-inflammatory effective amount of:
- (a) a compound having the formula:
- wherein:
- R1 is C1-C7 alkyl;
- Z is carbonyl or β-hydroxymethylene;
- X is Cl or F;
- and the dotted line in ring A indicates that the 1,2-linkage is saturated or unsaturated;
- and
- (b) a compound having the formula:
- wherein:
- R is H or C1-C4 alkyl;
- Z1 is carbonyl or β-hydroxymethylene;
- X1 is —O— or —S—;
- R5 is —OH, —OR6, —OCOOR6 or —OCOR7 wherein R6 is C1-C4 alkyl and R7 is
- C1-C4 alkyl, fluoromethyl or chloromethyl;
- and the dotted line is defined as above;
- with the proviso that when R is C1-C4 alkyl, then R5 is —OH;
- the amount of compound of formula (II) being sufficient to enhance the anti-inflammatory activity or duration of action, or both, of said compound of formula (I);
- and
- (2) a non-toxic, pharmaceutically acceptable carrier therefor suitable for topical or other local application;
- with the proviso that [3H]-triamincolone acetonide is excluded from the composition.
A method for alleviating inflammation in or on a warm-blooded animal exhibiting a topical or other localized inflammatory response, which comprises topically or otherwise locally administering to said animal an anti-inflammatory effective amount of a pharmaceutical composition comprising:
- (1) a combined synergistic anti-inflammatory effective amount of:
- (a) loteprednol etabonate;
- and
- (b) a compound having the formula:
- wherein R is H or C1-C4 alkyl and the dotted line in ring A indicates that the 1,2-linkage is saturated or unsaturated, the amount of compound of formula (IIa) being sufficient to enhance the anti-inflammatory activity or duration of action, or both, of loteprednol etabonate;
- and
- (2) a non-toxic, pharmaceutically acceptable carrier therefor suitable for topical or other local application;
- with the proviso that [3H]-triamcinolone acetonide is excluded from the composition.
Dependencies are inferred from the claim text.