Nelson Research & Development Company

Other

Whitby Research, Inc.

Vithal J Rajadhyaksha

James V Peck

Gevork Minaskanian

Richard Allen Schroer

Phillip J Brock

Earl R Krueger

Richard S Graham

Margarita L Dubocovich

Atef A Helmy

Nathan L Smith, Iii

William D Fairbairn

Julia J Chouw

Nelly M Rajadhyaksha

A method and compositions for enhancing absorption of topically administered physiologically active agents through the skin and mucous membranes of humans and animals in a transdermal device or formulation for local or systemic use, comprising a therapeutically effective amount of a pharmaceutically active agent and a non-toxic, effective amount of penetration enhancing agent of the formula I or a physiologically acceptable salt thereof: ##STR1## wherein: R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined herein.

Compositions and method comprising aminoalcohol derivatives as membrane

This invention relates to novel melatonin derivatives, such as 2-aryl substituted N-acetyltryptamines, having pharmacological activity, e.g., melatonin antagonist activity, and methods for the synthesis thereof.

2-aryl substituted N-acetyltryptamines and process of preparing such

This invention relates to a method for administering systemically active agents including therapeutic agents through the skin or mucosal membranes of humans and animals in a transdermal device or formulation comprising topically administering with said systemic agent an effective amount of a membrane penetration enhancer having the structural formula ##STR1## wherein X is selected from the group consisting of oxygen and sulfur; R' is H or a lower alkyl group having 1-4 carbon atoms; m is 2-6; n is 0-17 and R is --CH.sub.3 ; wherein R is H or a lower alkyl group, m is 5-7 and n is 0-17.

Penetration enhancers for transdermal delivery of systemic agents

Pharmaceutical compositions for enhancing absorption of a topically administered formulation through dermal or mucosal membrane, for local or systemic application, comprising one or more agents of formula I: ##STR1## where: R is a saturated or unsaturated, straight or branched, cyclic or acyclic hydrocarbon group with from 1 to 19 carbon atoms or an alkoxyalkyl group; n is 2-20; X is selected from H, OR.sub.2 or NR.sub.2 R.sub.3 ; wherein R.sub.1, R.sub.2 and R.sub.3 are independently selected from H, alkyl, haloalkyl, acyl, carbalkoxy, carbalkoxyalkyl, hydroyalkyl, acyloxyalkyl, alkoxyalkyl, aminoalkyl- and acylaminoalkyl; i) with the proviso that when n is 2, X is OR.sub.2 and R.sub.2 is H, then R.sub.1 is not hydroxyalkyl, specifically, 2-hydroxyethyl; and ii) with the proviso that when n is 2 and X is NR.sub.2 R.sub.3, then R.sub.1 and R.sub.2 may combine to form a heterocyclic ring and R.sub.3 is not acyl; and iii) with the proviso that when X is NR.sub.2 R.sub.3, then R.sub.2 and R.sub.3 may combine to form a heterocyclic ring; iv) with the proviso that when R is an alkoxyalkyl group then X may be hydrogen and when X is not hydrogen, and v) with the proviso that when X is H, R is not alkyl and R.sub.1 is not H and alkyl then R.sub.1 and X may combine to form heterocyclic ring and methods of using the same are disclosed.

Penetration enhancers

Compositions useful for carrying physiologically active agents such as therapeutic agents through skin and other body membranes comprising the agent and an effective, non-toxic amount of a compound having the structural formula ##STR1## wherein R' is H or a lower alkyl group, m is 3, N is 6-11 and R is --CH.sub.3. ##STR2##

Vehicle composition containing 1-substituted azacycloalkan-2-ones

A method and compositions for enhancing absorption of topically administered physiologically active agents through the skin and mucous membranes of humans and animals in a transdermal device or formulation for local or systemic use, comprising a therapeutically effective amount of a pharmaceutically active agent and a non-toxic, effective amount of penetration enhancing agent of the formula I: ##STR1## wherein R is a saturated or unsaturated, straight or branched, cyclic or acyclic hydrocarbon group with from 1 to 19 carbon atoms, alkoxyalkyl, haloalkyl, specifically trifluoromethyl, alkoxy, amino, alkylamino and acylamino; R' and R' are hydrogen, alkyl, trifluoromethyl, alkoxyalkyl, aminoalkyl, alkyl- and acylaminoalkyl, carboxy, carbalkoxy, hydroxyalkyl or lower alkyl ester thereof; X is O or NR.sub.1 wherein R.sub.1 is hydrogen, alkyl, alkenyl, alkoxyalkyl, carbalkoxyalkyl, aminoalkyl, alkyl- and acylaminoalkyl, hydroxyalkyl or hydroxyalkyloxyalkyl and lower alkyl ester thereof; and n is 2 or 3 are disclosed.

Compositions and method comprising heterocyclic compounds containing two

Compositions for carrying physiologically active agents through body membranes having the structural formula I: ##STR1## where: R=H, Alkyl group containing from 1-18 carbon atoms, cycloalkyl, aryl, aralkyl, alkoxy, hydroxyalkyl, alkoyloxyalkyl, acyloxyalkyl and alkoxyalkyl;

Oxazolidinone penetration enhancing compounds

A method and compositions for topically administering physiologically active agents through the skin and mucous membranes of humans and animals in a transdermal device or formulation for systemic use or to the skin of humans and animals for localized use comprising applying to such skin or membrane a mixture of said physiologically active agent and a non-toxic, effective penetrating amount of penetration enhancing compound having the structural formula I: ##STR1## wherein: R is a saturated or unsaturated hydrocarbon group with from 5 to 19 carbon atoms; R' and R' are hydrogen, lower alkyl, trifluoromethyl, lower hydroxyalkyl or lower alkyl ester of lower hydroxyalkyl, with the proviso that both R' and R' are not lower hydroxyalkyl; X is O or NR.sub.1 ; R.sub.1 being hydrogen, lower alkyl, lower alkenyl, lower hydroxyalkyl or lower alkyl ester of lower hydroxyalkyl are disclosed.

Compounds having calcium channel antagonist activity of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are each independently amino, trifluoromethyl, pentafluoroethyl, alkoxy, lower alkenyl, or lower alkynyl or branched or unbranched lower alkyl, which is unsubstituted or is substituted with cyano, hydroxy, acyloxy, hydrazino, lower alkyl amino, or di(lower alkyl)-amino or 5 or 6 membered saturated nitrogen-containing heterocyclic-1-yl, which is unsubstituted or is substituted with oxo, hydroxy, alkyl, and hydroxy (lower alkyl) R.sub.3 is straight- or branched-chain C.sub.1 to C.sub.12 alkyl, alkenyl, alkynyl, or cycloalkyl, and is either unsubstituted or substituted with hydroxy, acyloxy, cyano, di(lower alkyl) amino 5- or 6-membered saturated nitrogen-containing heterocyclic -1-yl or R.sub.3 is --A--R.sub.4, A is a straight- or branched-chain hydrocarbon moiety containing from 2 to 12 carbon atoms and from 0 to 2 double bonds, R.sub.4 is selected from the group consisting of: ##STR2## R.sub.5 is hydrogen, nitro, cyano, azido, amino, trifluoromethyl, alkylamino, dialkylamino, halo, carboxyl, carbalkoxy, alkyl, alkenyl, alkynyl, cycloalkyl, acylamino, carboxamido, sulfonamido, and SO.sub.m -(lower)alkyl where m is 0, 1, or 2 and R.sub.6 is aryl or heteroaryl or a pharmaceutically-acceptable salt thereof are disclosed. Also disclosed is a method of treating hypertension and other disorders by administering an effective amount of a compound of the present invention.

1,4-dihydropyridines

The disclosure describes compositions and methods for improved delivery of plant growth regulators comprising contacting a plant with a composition comprising an effective amount of a plant growth regulator and an effective delivery enhancing amount of compound having the structural formula ##STR1## wherein R' is H or a lower alkyl group having 1-4 carbon atoms, m is 3-7, n is 0-17 and R is --CH.sub.3, ##STR2## where R' is H or halogen, with the proviso that if m is 3 and R is CH.sub.3, then n is 5-17.

Delivery of plant growth regulators

The coating of surfaces to impart gloss and protect from weathering, and the use of solvents in paint formulations, are disclosed; the following being exemplary: Compounds having the formula: ##STR1## wherein R.sub.1, R.sub.2, and R.sub.3 are saturated alkyls having from 2 to 20 carbon atoms therein. R.sub.1 and R.sub.2, or R.sub.2 and R.sub.3, alternatively, may be the same and form a nitrogen heterocyclic compound such as that derived from, for example, a pyrrolidine, a piperidine or a hexahydroazepine. Exemplary compounds include: N,N-diethyldodecanamide; N,N-di-n-propyldodecanamide; 1-dodecly-2-pyrrolidone; 1-dodecyl-2-piperidone; 1-dodcylhexahydro-2H-azepin-2-one; 1-dodecanoylpiperidine; 1-dodecanoylpyrrolidone; 1-dodecanoylhexahydroazepine; N,N-diethylhexadecanamide; N,N-di-n-propylhexadecanamide; 1-hexadecyl-2-pyrrolidone; 1-hexadecyl-2-piperidone; 1-hexadecylhexahydro-2H-azepin-2-one; 1-hexadecanoylpyrrolidine; 1-hexadecanoylpiperidine; 1-hexadecanoylhexahydroazepine; N,N-dioctylbutanamide; N,N-didodecylbutanamide. N-dodecyl-N-butylethanamide and N-ethyl-N-hexadecylpropanamide.

Water proofing and preservative methods

Compounds having calcium channel antagonist activity of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are each independently amino, trifluoromethyl, pentafluoroethyl, alkoxy, lower alkenyl, or lower alkynyl or branched or unbranched lower alkyl, which is unsubstituted or is substituted with cyano, hydroxy, acyloxy, hydrazino, lower alkyl amino, or di(lower alkyl)-amino or 5 or 6 membered saturated nitrogen-containing heterocyclic-1-yl, which is unsubstituted or is substituted with oxo, hydroxy, alkyl, and hydroxy (lower alkyl) R.sub.3 is straight- or branched-chain C.sub.1 to C.sub.12 alkyl, alkenyl, alkynyl, or cycloalkyl, and is either unsubstituted or substituted with hydroxy, acyloxy, cyano, di(lower alkyl) amino 5- or 6-membered saturated nitrogen-containing heterocyclic-1-yl or R.sub.3 is --A-R.sub.4, A is a straight- or branched-chain hydrocarbon moiety containing from 2 to 12 carbon atoms and from 0 to 2 double bonds, R.sub.4 is selected from the group consisting of: ##STR2## R.sub.5 is hydrogen, nitro, cyano, azido, amino, trifluoromethyl, alkylamino, dialkylamino, halo, carboxyl, carbalkoxy, alkyl, alkenyl, alkynyl, cycloalkyl, acylamino, carboxamido, sulfonamide, and SO.sub.m -(lower)alkyl where m is 0, 1, or 2 and R.sub.6 is aryl or heteroaryl or a pharmaceutically-acceptable salt thereof are disclosed. Also disclosed is a method of treating hypertension and other disorders by administering an effective amount of a compound of the present invention.

Calcium antagonist N-hetero ester 1,4-dihydropyridines

In a method for administering systemically active agents including therapeutic agents through the skin or other body membranes of humans and animals typically in the form of a transdermal device or formulation, the improvement comprising the use therewith of an effective amount of a membrane penetration enhancer having the structural formula. ##STR1## wherein R is H or a lower alkyl group, m is 5-7 and n is 0-17.

Penetration enhancers for transdermal drug delivery of systemic agents

The disclosure describes compositions and methods for improved delivery of plant nutrients comprising contacting a plant with a composition comprising an effective amount of a plant nutrient and an effective delivery enhancing amount of compound having the structural formula ##STR1## wherein R' is H or a lower alkyl group having 1-4 carbon atoms, m is 3-7, n is 0-17 and R is --CH.sub.3, ##STR2## where R' is H or halogen, with the proviso that if m is 3 and R is CH.sub.3, then n is 5-17.

Delivery of plant nutrients

Compositions useful for carrying physiologically active agents such as therapeutic agents through skin and other body membranes comprising the agent and an effective, non-toxic amount of a compound having the structural formula ##STR1## wherein R' is H or a lower alkyl group, m is 3-7, N is 0-17 and R is --CH.sub.3, phenyl or substituted phenyl or ##STR2## with the proviso that if m is 3 and R is --CH.sub.3, then n is not 0-6.

Growing community of inventors

Mission Viejo, CA, United States of America

Vithal J Rajadhyaksha