US2004122105A1PendingUtilityA1
Transdermal compositions
Priority: Sep 20, 2002Filed: Sep 22, 2003Published: Jun 24, 2004
Est. expirySep 20, 2022(expired)· nominal 20-yr term from priority
A61P 39/06A61P 35/00A61P 31/02A61P 31/00A61P 3/02C07C 233/05A61K 8/42A61L 26/0066A61K 36/87A61Q 17/00A61L 2300/802A61Q 19/00A61K 47/12A61K 36/58A61K 47/18A61K 31/164A61K 36/45A61K 9/0014A61Q 5/12A61Q 17/005A61L 2300/22A61L 2300/208A61K 31/205A61P 17/00A61P 17/02A01N 25/00A61L 2300/404A61K 45/06A61P 1/00
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Claims
Abstract
The present invention is directed to transdermal compositions and the uses thereof. These compositions include at least one of the following components: a C 1 -C 6 dialkyl, C 12 -C 30 dialkyl quaternary ammonium salt, a C 12 -C 30 fatty acid, a nitrogenous organic base, C 12-30 fatty alcohol, monoglyceride or the reaction products thereof.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A tertiary amide of the formula:
or pharmaceutically acceptable salts thereof PS wherein R 4 is a fatty group of 11-29 carbon atoms;
R 5 and R 6 are independently lower alkyl aryl, aryl lower alkyl, or fatty group containing 11-29 carbon atoms or R 7 ;
R 7 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 2 and R 3 are independently lower alkylene groups containing 1-6 carbon atoms,
R 1 is a lower alkyl, and
Ar is aryl.
2 . The tertiary amide of claim 1 wherein R 4 is a fatty group containing 15-21 carbon atoms.
3 . The tertiary amide of claim 1 wherein R 5 is aryl or aryl lower alkyl; and R 6 is
R 1 —Ar—O—R 2 —O—R 3 —; R 2 and R 3 are independently alkylene containing 1-3 carbon atoms; and Ar is aryl
4 . The tertiary amide according to claim 3 wherein Ar is phenyl.
5 . The tertiary amide according to claim 4 wherein R 5 is aryl lower alkyl.
6 . The tertiary amide according to claim 5 wherein R 5 is benzyl.
7 . The tertiary amide according to claim 5 wherein R 4 is saturated.
8 . The tertiary amide according to claim 5 wherein 14 is unsaturated.
9 . The tertiary amide according to claim 8 wherein R 4 contains 1-8 carbon-carbon double bonds.
10 . The tertiary amide according to claim 1 which is distearyl stearamide, distearyl linoleamide, benzethonium linoleamide or benzethonium stearamide.
11 . A mixture comprising a tertiary amide of a formula
or pharmaceutically acceptable salts and a quaternary ammonia salt of the formula
wherein R 5 , R 6 , R 9 and R 10 are independently lower alkyl, aryl lower alkyl, R 7 or fatty group containing 11-29 carbon atoms, wherein at least one of R 5 , R 6 , R 9 and R 10 is a fatty group and each of said fatty group is an aliphatic group which may be completely saturated or contain 1-8 carbon-carbon double bonds;
R 7 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 1 is alkyl containing 1-15 carbon atoms;
R 2 and R 3 are independently lower alkylene and
X is a counterion.
12 . A method for treating insect bites on a mammal which comprises applying topically to the mammal in the locus of the insect bite an amount effective of a quaternary ammonium salt for treating insect bites of the formula
wherein R 5 , R 6 , R 9 and R 10 are independently lower alkyl or fatty group, aryl lower alkyl or R 7 wherein at least one of R 5 , R 6 , R 9 and R 10 is a fatty group, each of said fatty group containing 11-29 carbon atoms and may be completely saturated or contain 1-8 carbon-carbon double bonds,
R 7 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 1 is alkyl containing 1-15 carbon atoms,
R 2 and R 3 are independently lower alkylene, and
X is a counter ion.
13 . The method according to claim 12 wherein R 9 and R 10 are lower alkyl and R 5 and R 6 are fatty groups.
14 . The method according to claim 12 wherein R 10 and R 9 are lower alkyl and R 5 and R 6 are fatty groups containing 15-21 carbon atoms.
15 . The method according to claim 14 wherein R 5 and R 6 are independently saturated fatty group.
16 . The method according to claim 14 wherein R 5 and R 6 are independently unsaturated fatty group.
17 . The method according to claim 12 wherein an anti-oxidant is additionally present.
18 . A pharmaceutical composition comprising an effective amount of the reaction product of the quaternary ammonium salt of the formula
and a fatty acid of the formula R 8 COOH in an aqueous solvent under conditions effective to form an ion pair between said quaternary ammonium salt and fatty acid wherein R 5 , R 6 , R 9 and R 10 are independently lower alkyl, aryl, aryl lower alkyl, fatty group, or R 7 , wherein at least one of R 5 , R 6 , R 9 and R 10 are a fatty group, said fatty group is an aliphatic group containing 1′-29 carbon atoms and 0-8 carbon-carbon double bonds;
R 7 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 1 is alkyl containing 1-15 carbon atoms;
R 2 and R 3 are independently lower alkylene and X is a counterion;
R 8 is a fatty group containing 11-29 carbon atoms;
wherein the molar ratio of the quaternary ammonium salt to fatty acid ranges from about 1:10 to about 10:1.
19 . The pharmaceutical composition according to claim 18 wherein R 5 and R 6 are independently a fatty group and R 9 and R 10 are lower alkyl.
20 . The pharmaceutical composition according to claim 19 wherein the fatty group contains 15-21 carbon atoms.
21 . The pharmaceutical composition according to claim 18 wherein R 9 and R 10 are independently alkenyl groups containing 15-21 carbon atoms and one, two, three, four, five or six carbon-carbon double bonds.
22 . The pharmaceutical composition according to claim 18 wherein the molar ratio of ammonium salt to fatty acid from about 1:5 to about 5:1.
23 . The pharmaceutical composition according to claim 22 wherein the ratio ranges from about 1:2 to about 2:1.
24 . The pharmaceutical composition according to claim 23 wherein the ratio is about 1:1.
25 . A method for killing microorganism on the surface of objects which comprises applying the pharmaceutical composition of claim 18 to the surface of said object.
26 . A carrier composition for association with a topical pharmaceutical composition wherein said carrier composition comprises a skin penetrating effective amount of the tertiary amide of claim 1 .
27 . A pharmaceutical composition comprising a pharmaceutically effective amount of a drug in association with a transdermal carrier, said transdermal carrier comprising the tertiary amide of claim 1 .
28 . A method for enhancing the penetration of a drug through the skin of a mammal which comprises mixing the drug with a skin penetrating effective amount of the tertiary amide of claim 1 .
29 . The method according to claim 27 wherein the tertiary amide is present in the pharmaceutical composition in an amount ranging from about 0.3% to about 10% by weight of the pharmaceutical composition.
30 . The method according to claim 27 wherein the weight ratio of the tertiary amide to the active drug is greater than 20.
31 . The method according to claim 27 wherein R 4 is unsaturated.
32 . The method according to claim 27 wherein R 5 is lower arylalkyl and R 6 is R 1 —Ar—O—R 2 —O—R 3 .
33 . The method according to claim 32 wherein Ar is phenyl.
34 . The method according to claim 31 wherein R 5 is benzyl and Ar is phenyl.
35 . A mixture comprising two or more different tertiary amides of the formula
or pharmaceutically acceptable salts thereof wherein
R 4 is a fatty group of 11-29 carbon atoms;
R 5 and R 6 are independently lower alkyl aryl, aryl lower alkyl, or fatty group containing 11-29 carbon atoms or R 7 ;
R 7 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 2 and R 3 are independently lower alkylene groups containing 1-6 carbon atoms,
R 1 is a lower alkyl, and
Ar is aryl.
36 . The mixture of claim 34 wherein in at least one of the tertiary amides, R 5 is an unsaturated fatty group and R 6 is an aryl, aryl lower alkyl or R 7 .
37 . A multi-layered pharmaceutical composition comprising a first layer comprised of the tertiary amide of claim 1 , a second layer comprised of a non-ionic surfactant, a third layer comprised of nutrients and a top layer comprised of a water soluble polymer.
38 . The multi-layered pharmaceutical composition according to claim 36 which additionally comprises a wax layer, said wax layer located between the water soluble polymer and the surfactant layer.
39 . The multi-layer pharmaceutical composition according to claim 36 wherein the top layer is povidone.
40 . A method for protecting the skin of a mammal from chafing, chapping or contact dermatitis comprising applying to the skin of said mammal, a layered composition comprising the lower layer comprised of a tertiary amide of claim 1 , a second layer comprising a non-ionic surfactant and nutrients for the skin, and the top layer comprising a water soluble polymer.
41 . The method according to claim 40 wherein the layered composition additionally comprises a wax layer, said wax layer located between the water soluble polymer and the surfactant/nutrient layer.
42 . A product prepared by the process comprising:
(a) reacting a fatty alcohol containing 12-30 carbon atoms with a fatty acid containing 12-30 carbon atoms under esterfication conditions to form a first fatty acid ester; (b) reacting glycerol with a second fatty acid under esterfication conditions to form a monoglyceride; (c) reacting the product of step (a) with the product of step (b) under conditions effective condition to form an ether.
43 . The product according to claim 42 having the formula
wherein R 100 is fatty groups having 11-29 carbon atoms and R 101 and R 102 are independently a fatty group having 12-30 carbon atoms.
44 . The product according to claim 42 wherein the first and second fatty acids contain 16-22 carbon atoms.
45 . A carrier composition comprising the product of claim 42 .
46 . A carrier composition comprising the product of claim 44 .
47 . A method for enhancing the penetration of a drug through the skin of a mammal which comprises mixing the drug with a skin penetrating effective amount of the product of claim 42 .
48 . The method according to claim 47 wherein the product has the formula
wherein R 100 is fatty groups having 11-29 carbon atoms and R 101 and R 102 are independently a fatty group having 12-30 carbon atoms.
49 . The product of claim 42 admixed with quaternary ammonium salt of the formula
wherein R 5 , R 6 , R 9 and R 10 are independently lower alkyl, fatty group, aryl lower alkyl or R 7 wherein at least one of R 5 , R 6 , R 9 and R 10 is a fatty group, each of said fatty group containing 11-29 carbon atoms and may be completely saturated or contain 1-8 carbon-carbon double bonds,
R 7 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 1 is alkyl containing 1-15 carbon atoms,
R 2 and R 3 are independently lower alkylene, and
X is a counter ion.
50 . A carrier composition comprising the product of claim 42 admixed with a quaternary ammonium salt of the formula
wherein R 5 , R 6 , R 9 and R 10 are independently lower alkyl, fatty group, aryl lower alkyl or R 7 wherein at least one of R 5 , R 6 , R 9 and R 10 is a fatty group, each of said fatty group containing 11-29 carbon atoms and may be completely saturated or contain 1-8 carbon-carbon double bonds, R 7 is
R 1 —Ar—O—R 2 —O—R 3 —;
R 1 is alkyl containing 1-15 carbon atoms,
R 2 and R 3 are independently lower alkylene, and
X is a counter ion.
51 . A pharmaceutical composition for topical application comprising a pharmaceutically effective amount of a drug and the carrier composition of claim 50 .
52 . The pharmaceutical composition according to claim 50 wherein the drug and the carrier are present in a molar ratio of drug to carrier of greater than about 20.
53 . The pharmaceutical composition according to claim 51 wherein the drug and the carrier are present in a molar ratio of between about 5 and about 20.
54 . A method for treating skin sores, chapping, chafing, skin bruises or wounds on a mammal which comprises applying to the locus of the skin injury a pharmaceutical composition comprising a pharmaceutically effective amount of a drug and a skin penetrating effective amount of a carrier composition according to claim 26 or 42 .
55 . The pharmaceutical composition according to claim 54 wherein the drug and the carrier are present in a molar ratio of drug to carrier ranging from between about 5 to about 20.
56 . A pharmaceutical composition for treating sun-damaged skin comprising a pharmaceutical effective amount of a drug for treating said sun-damaged skin in association with a transdermal carrier capable of penetrating the skin of a mammal, said transdermal carrier comprising of a skin penetrating effective amount of a tertiary amide according to claim 1 and a water extract of lilium longiflorum.
57 . A transdermal carrier comprising a skin penetrating effective amount of tertiary amide according to claim 1 and an ion pair prepared by the reaction of a quaternary ammonium salt and a fatty acid and under conditions effective to form a quaternary ammonium salt; fatty acid ion pair.
58 . The carrier according to claim 57 wherein the molar ratio of tertiary amide to ion pair ranges from about 1:1 to about 8:1.
59 . The carrier according to claim 57 wherein the molar ratio is about 4:1.
60 . The carrier composition according to claim 59 wherein the molar ratio is about 1:2.
61 . A method for treating chapped or cracked skin on a mammal comprising a quaternary ammonium product, and a carrier composition according to claim 26 or 42 .
62 . An amide hydrate of the tertiary amide of any one of claims 1 - 10 .
63 . A gel comprising the tertiary amide of any one of claims 1 - 10 .Join the waitlist — get patent alerts
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