US 7,604,797 B2Granted

Compositions and methods for treating burns

AssigneeBioMechanisms Inc.

InventorTerry Lee Hicks

Life of this patent

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Abstract

The present invention provides compositions and methods for treating burns comprising administering to a burn area of a subject in need thereof of a therapeutically effective amount of a composition comprising an anti-cytokine or anti-inflammatory agent or a functional derivative thereof; and a pharmaceutically acceptable excipient.

Claims43

Dependent claims

A method for reducing the severity of inflammation and edema associated with a burn injury, comprising administering a pharmaceutical composition to a mammal having a burn injury in need thereof, the pharmaceutical composition comprising:

a) a therapeutically effective amount of sodium monofluorophosphate;
b) a therapeutically effective amount of a dihydrofolate reductase inhibitor selected from the group consisting of aminopterin, methotrexate, pyramethamine, trimethoprim, a functional derivative of aminopterin, and a functional derivative of methotrexate, wherein the functional derivatives of aminopterin are selected from the group consisting of 3′,5′-dichloroaminopterin;
5,8-dideaza 5,6,7,8-tetrahydroaminopterin;
5,8,10-trideazaminopterin;
5,10-dideazatetrahydrofolic acid;
8,10-dideazaminopterin;
aminopterin-gamma-hydrazide;
aminopterin-alpha-hydrazide;
3′,5′-dichloraminopterin-gamma-hydrazide;
3′,5′-dichloroaminopterin-alpha-hydrazide;
aminopterin-gamma-tyrosyl-hydrazide;
aminopterin alpha-alpha-lysyl-glycyl-tyrosyl-hydrazide;
aminopterin-alpha-alpha-lysyl hydrazide;
aminopterin-alpha-alpha-lysine;
aminopterin-alpha-alpha-lysyl-epsilon-arginine-glycine-glycine-tyrosine (SEQ ID NO:
3);
alpha-methyl, alpha-ethyl, alpha-propyl, alpha-butyl, alpha-pentyl, alpha-hexyl, alpha-heptyl, alpha-octyl, and alpha-benzyl carboxylesters of aminopterin;
alpha-amide, alpha-butylamide, alpha-benzylamide, and alpha-amidoethane sulfonic acid carboxylamides of aminopterin;
alpha-glycyl, alpha-aspartyl, alpha-glutamyl, and alpha-polyglutamyl carboxylpeptides of aminopterin;
gamma-methylester, gamma-ethylester, gamma-propylester, gamma-butylester, gamma-pentylester, gamma-hexylester, gamma-heptylester, gamma-octylester, and gamma-benzylester alpha-carboxylhydrazide-gamma-carboxylesters of aminopterin;
gamma-amide, gamma-butylamide, gamma-benzylamide, and gamma-amidoethane sulfonic acid carboxylamides of aminopterin;
gamma-glycyl, gamma-aspartyl, gamma-glutamyl, and gamma-polyglutamyl carboxylpeptides of aminopterin;
gamma-carboxylhydrazides of aminopterin;
alpha-gamma-dimethylester, alpha-gamma-diethylester, alpha-gamma-dipropylester, alpha-gamma-dibutyl ester, alpha-gamma-dipentyl ester, alpha-gamma-dihexylester, alpha-gamma diheptylester, alpha-gamma-dioctylester, and alpha-gamma-dibenzylester dicarboxylesters of aminopterin;
alpha-gamma-diamide, alpha-gamma-dibenzylamide, and alpha-gamma-diamidomethane sulfonic acid dicarboxylamides of aminopterin;
alpha-gamma-diglycyl, alpha-gamma-diaspartyl, alpha-gamma-diglutamyl, and alpha-gamma-dipolyglutamyl dicarboxylpeptides of aminopterin;
alpha-gamma-dicarboxylhydrazides of aminopterin;
alpha-methylester-gamma-butylester, and alpha-methylester-gamma-benzylester dicarboxylesters of aminopterin;
alpha-benzylester-gamma-butylamide, alpha-benzylester-gamma-benzylamide, alpha-benzylester-gamma-butylamide-p-toluene sulfonic acid, and alpha-benzylester-gamma-benzylamide-p-toluene sulfonic acid alpha-ester-gamma-amides of aminopterin;
alpha-t-butylester-gamma-hydrazides of aminopterin;
alpha-ester-gamma-peptides of aminopterin;
alpha-amide-gamma-esters of aminopterin;
alpha-amide-gamma-peptides of aminopterin;
alpha-amide-gamma-hydrazides of aminopterin;
alpha-peptide-gamma-esters of aminopterin;
alpha-peptide-gamma-amides of aminopterin;
alpha-peptide-gamma-hydrazides of aminopterin;
alpha-hydrazide-gamma-amides of aminopterin;
and alpha-hydrazide-gamma-peptides of aminopterin;
and the functional derivatives of methotrexate are selected from the group consisting of 4-amino-4-deoxy-N10-methylpteroyl-D,L-homocysteic acid (mAPA-D,L-HCysA);
4-amino-4-deoxy-N10-methylpteroyl-L-cysteic acid (mAPA-L-CysA);
4-amino-4-deoxy-N10-methylpteroyl-L-homocysteic acid (mAPA-L-HCysA);
4-amino-4-deoxypteroyl-D,L-homocysteic acid (APA-D,L-HCysA);
4-amino-4-deoxypteroyl-L-cysteic acid (APA-L-CysA);
4-amino-4-deoxypteroyl-L-homocysteic acid (APA-L-HCysA);
3′,5′-dichloromethotrexate;
5,8-dideaza-5,6,7,8-tetrahydromethotrexate;
methotrexate-gamma hydrazide;
methotrexate-alpha-hydrazide;
3′5′-dichloromethotrexate-gamma-hydrazide;
3′,5′-dichloromethotrexate-alpha-hydrazide;
methotrexate-alpha-alpha-lysyl-glycyl-glycyl-tyrosyl hydrazide (SEQ ID NO:
1);
methotrexate-gamma-tyrosyl hydrazide;
methotrexate-alpha-alpha-lysyl hydrazide;
methotrexate-alpha-alpha-lysine;
methotrexate-alpha-alpha-lysyl-epsilon-arginine-glycine-glycine-tyrosine (SEQ ID NO:
2);
5,8-dideazamethotrexate;
alpha-methyl, alpha-ethyl, alpha-propyl, alpha-butyl, alpha-pentyl, alpha-hexyl, alpha-heptyl, alpha-octyl, and alpha-benzyl carboxylesters of methotrexate;
alpha-amide, alpha-butylamide, alpha-benzylamide, and alpha-amidoethane sulfonic acid carboxylamides of methotrexate;
alpha-glycyl, alpha-aspartyl, alpha-glutamyl, and alpha-polyglutamyl carboxylpeptides of methotrexate;
gamma-methylester, gamma-ethylester, gamma-propylester, gamma-butylester, gamma-pentylester, gamma-hexylester, gamma-heptylester, gamma-octylester, and gamma-benzylester alpha-carboxylhydrazide-gamma-carboxylesters of methotrexate;
gamma-amide, gamma-butylamide, gamma-benzylamide, and gamma-amidoethane sulfonic acid carboxylamides of methotrexate;
gamma-glycyl, gamma-aspartyl, gamma-glutamyl, and gamma-polyglutamyl carboxylpeptides of methotrexate;
gamma-carboxylhydrazides of methotrexate;
alpha-gamma-dimethylester, alpha-gamma-diethylester, alpha-gamma-dipropylester, alpha-gamma-dibutyl ester, alpha-gamma-dipentyl ester, alpha-gamma-dihexylester, alpha-gamma diheptylester, alpha-gamma-dioctylester, and alpha-gamma-dibenzylester dicarboxylesters of methotrexate;
alpha-gamma-diamide, alpha-gamma-dibenzylamide, and alpha-gamma-diamidomethane sulfonic acid dicarboxylamides of methotrexate;
alpha-gamma-diglycyl, alpha-gamma-diaspartyl, alpha-gamma-diglutamyl, and alpha-gamma-dipolyglutamyl dicarboxylpeptides of methotrexate;
alpha-gamma-dicarboxylhydrazides of methotrexate;
alpha-methylester-gamma-butylester, and alpha-methylester-gamma-benzylester dicarboxylesters of methotrexate;
alpha-benzylester-gamma-butylamide, alpha-benzylester-gamma-benzylamide, alpha-benzylester-gamma-butylamide-p-toluene sulfonic acid, and alpha-benzylester-gamma-benzylamide-p-toluene sulfonic acid alpha-ester-gamma-amides of methotrexate;
alpha-t-butylester-gamma-hydrazides of methotrexate;
alpha-ester-gamma-peptides of methotrexate;
alpha-amide-gamma-esters of methotrexate;
alpha-amide-gamma-peptides of methotrexate;
alpha-amide-gamma-hydrazides of methotrexate;
alpha-peptide-gamma-esters of methotrexate;
alpha-peptide-gamma-amides of methotrexate;
alpha-peptide-gamma-hydrazides of methotrexate;
alpha-hydrazide-gamma-amides of methotrexate;
and alpha-hydrazide-gamma-peptides of methotrexate;
and
c) a pharmaceutically acceptable carrier.

81 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/012,210Filed 16 Dec 2004 · continuation
Priority: 30 Sep 2003
Published: US 2005/0281820 A122 Dec 2005
Granted: 20 Oct 2009
Term ends: Not estimatedThe source records don’t support an estimate.

Classification48 codes

A61K 31/34
Having oxygen as the only ring hetero atom, e.g. fungichromin: having five-membered rings with one oxygen as the only ring hetero atom, e.g.…
A61K 9/0014
Galenical forms characterised by the site of application: skin, i.e. galenical aspects of topical compositions
A61K 9/06
Medicinal preparations characterised by special physical form: ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
A61K 31/355
3,4-Dihydrobenzopyrans, e.g. chroman, catechin: tocopherols, e.g. vitamin E

Family

Application60/506,745Us provisional application · filed 30 Sep 2003
PCT/US2004/031917Parent of this continuation · filed 30 Sep 2004
US 2005/0281820 A1Pre-grant publication · published 22 Dec 2005
US 7,604,797 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

a) a therapeutically effective amount of sodium monofluorophosphate;
b) a therapeutically effective amount of a dihydrofolate reductase inhibitor selected from the group consisting of aminopterin, methotrexate, pyramethamine, trimethoprim, a functional derivative of aminopterin, and a functional derivative of methotrexate, wherein the functional derivatives of aminopterin are selected from the group consisting of 3′,5′-dichloroaminopterin;
5,8-dideaza 5,6,7,8-tetrahydroaminopterin;
5,8,10-trideazaminopterin;
5,10-dideazatetrahydrofolic acid;
8,10-dideazaminopterin;
aminopterin-gamma-hydrazide;
aminopterin-alpha-hydrazide;
3′,5′-dichloraminopterin-gamma-hydrazide;
3′,5′-dichloroaminopterin-alpha-hydrazide;
aminopterin-gamma-tyrosyl-hydrazide;
aminopterin alpha-alpha-lysyl-glycyl-tyrosyl-hydrazide;
aminopterin-alpha-alpha-lysyl hydrazide;
aminopterin-alpha-alpha-lysine;
aminopterin-alpha-alpha-lysyl-epsilon-arginine-glycine-glycine-tyrosine (SEQ ID NO:
3);
alpha-methyl, alpha-ethyl, alpha-propyl, alpha-butyl, alpha-pentyl, alpha-hexyl, alpha-heptyl, alpha-octyl, and alpha-benzyl carboxylesters of aminopterin;
alpha-amide, alpha-butylamide, alpha-benzylamide, and alpha-amidoethane sulfonic acid carboxylamides of aminopterin;
alpha-glycyl, alpha-aspartyl, alpha-glutamyl, and alpha-polyglutamyl carboxylpeptides of aminopterin;
gamma-methylester, gamma-ethylester, gamma-propylester, gamma-butylester, gamma-pentylester, gamma-hexylester, gamma-heptylester, gamma-octylester, and gamma-benzylester alpha-carboxylhydrazide-gamma-carboxylesters of aminopterin;
gamma-amide, gamma-butylamide, gamma-benzylamide, and gamma-amidoethane sulfonic acid carboxylamides of aminopterin;
gamma-glycyl, gamma-aspartyl, gamma-glutamyl, and gamma-polyglutamyl carboxylpeptides of aminopterin;
gamma-carboxylhydrazides of aminopterin;
alpha-gamma-dimethylester, alpha-gamma-diethylester, alpha-gamma-dipropylester, alpha-gamma-dibutyl ester, alpha-gamma-dipentyl ester, alpha-gamma-dihexylester, alpha-gamma diheptylester, alpha-gamma-dioctylester, and alpha-gamma-dibenzylester dicarboxylesters of aminopterin;
alpha-gamma-diamide, alpha-gamma-dibenzylamide, and alpha-gamma-diamidomethane sulfonic acid dicarboxylamides of aminopterin;
alpha-gamma-diglycyl, alpha-gamma-diaspartyl, alpha-gamma-diglutamyl, and alpha-gamma-dipolyglutamyl dicarboxylpeptides of aminopterin;
alpha-gamma-dicarboxylhydrazides of aminopterin;
alpha-methylester-gamma-butylester, and alpha-methylester-gamma-benzylester dicarboxylesters of aminopterin;
alpha-benzylester-gamma-butylamide, alpha-benzylester-gamma-benzylamide, alpha-benzylester-gamma-butylamide-p-toluene sulfonic acid, and alpha-benzylester-gamma-benzylamide-p-toluene sulfonic acid alpha-ester-gamma-amides of aminopterin;
alpha-t-butylester-gamma-hydrazides of aminopterin;
alpha-ester-gamma-peptides of aminopterin;
alpha-amide-gamma-esters of aminopterin;
alpha-amide-gamma-peptides of aminopterin;
alpha-amide-gamma-hydrazides of aminopterin;
alpha-peptide-gamma-esters of aminopterin;
alpha-peptide-gamma-amides of aminopterin;
alpha-peptide-gamma-hydrazides of aminopterin;
alpha-hydrazide-gamma-amides of aminopterin;
and alpha-hydrazide-gamma-peptides of aminopterin;
and the functional derivatives of methotrexate are selected from the group consisting of 4-amino-4-deoxy-N10-methylpteroyl-D,L-homocysteic acid (mAPA-D,L-HCysA);
4-amino-4-deoxy-N10-methylpteroyl-L-cysteic acid (mAPA-L-CysA);
4-amino-4-deoxy-N10-methylpteroyl-L-homocysteic acid (mAPA-L-HCysA);
4-amino-4-deoxypteroyl-D,L-homocysteic acid (APA-D,L-HCysA);
4-amino-4-deoxypteroyl-L-cysteic acid (APA-L-CysA);
4-amino-4-deoxypteroyl-L-homocysteic acid (APA-L-HCysA);
3′,5′-dichloromethotrexate;
5,8-dideaza-5,6,7,8-tetrahydromethotrexate;
methotrexate-gamma hydrazide;
methotrexate-alpha-hydrazide;
3′5′-dichloromethotrexate-gamma-hydrazide;
3′,5′-dichloromethotrexate-alpha-hydrazide;
methotrexate-alpha-alpha-lysyl-glycyl-glycyl-tyrosyl hydrazide (SEQ ID NO:
1);
methotrexate-gamma-tyrosyl hydrazide;
methotrexate-alpha-alpha-lysyl hydrazide;
methotrexate-alpha-alpha-lysine;
methotrexate-alpha-alpha-lysyl-epsilon-arginine-glycine-glycine-tyrosine (SEQ ID NO:
2);
5,8-dideazamethotrexate;
alpha-methyl, alpha-ethyl, alpha-propyl, alpha-butyl, alpha-pentyl, alpha-hexyl, alpha-heptyl, alpha-octyl, and alpha-benzyl carboxylesters of methotrexate;
alpha-amide, alpha-butylamide, alpha-benzylamide, and alpha-amidoethane sulfonic acid carboxylamides of methotrexate;
alpha-glycyl, alpha-aspartyl, alpha-glutamyl, and alpha-polyglutamyl carboxylpeptides of methotrexate;
gamma-methylester, gamma-ethylester, gamma-propylester, gamma-butylester, gamma-pentylester, gamma-hexylester, gamma-heptylester, gamma-octylester, and gamma-benzylester alpha-carboxylhydrazide-gamma-carboxylesters of methotrexate;
gamma-amide, gamma-butylamide, gamma-benzylamide, and gamma-amidoethane sulfonic acid carboxylamides of methotrexate;
gamma-glycyl, gamma-aspartyl, gamma-glutamyl, and gamma-polyglutamyl carboxylpeptides of methotrexate;
gamma-carboxylhydrazides of methotrexate;
alpha-gamma-dimethylester, alpha-gamma-diethylester, alpha-gamma-dipropylester, alpha-gamma-dibutyl ester, alpha-gamma-dipentyl ester, alpha-gamma-dihexylester, alpha-gamma diheptylester, alpha-gamma-dioctylester, and alpha-gamma-dibenzylester dicarboxylesters of methotrexate;
alpha-gamma-diamide, alpha-gamma-dibenzylamide, and alpha-gamma-diamidomethane sulfonic acid dicarboxylamides of methotrexate;
alpha-gamma-diglycyl, alpha-gamma-diaspartyl, alpha-gamma-diglutamyl, and alpha-gamma-dipolyglutamyl dicarboxylpeptides of methotrexate;
alpha-gamma-dicarboxylhydrazides of methotrexate;
alpha-methylester-gamma-butylester, and alpha-methylester-gamma-benzylester dicarboxylesters of methotrexate;
alpha-benzylester-gamma-butylamide, alpha-benzylester-gamma-benzylamide, alpha-benzylester-gamma-butylamide-p-toluene sulfonic acid, and alpha-benzylester-gamma-benzylamide-p-toluene sulfonic acid alpha-ester-gamma-amides of methotrexate;
alpha-t-butylester-gamma-hydrazides of methotrexate;
alpha-ester-gamma-peptides of methotrexate;
alpha-amide-gamma-esters of methotrexate;
alpha-amide-gamma-peptides of methotrexate;
alpha-amide-gamma-hydrazides of methotrexate;
alpha-peptide-gamma-esters of methotrexate;
alpha-peptide-gamma-amides of methotrexate;
alpha-peptide-gamma-hydrazides of methotrexate;
alpha-hydrazide-gamma-amides of methotrexate;
and alpha-hydrazide-gamma-peptides of methotrexate;
and
c) a pharmaceutically acceptable carrier.

81 more elements

Facts

Application

11/012,210Filed 16 Dec 2004 · continuation

Priority

30 Sep 2003

Published

US 2005/0281820 A122 Dec 2005

Granted

20 Oct 2009

Term ends

Not estimatedThe source records don’t support an estimate.

Classification48 codes

A61K 31/34
Having oxygen as the only ring hetero atom, e.g. fungichromin: having five-membered rings with one oxygen as the only ring hetero atom, e.g.…
A61K 9/0014
Galenical forms characterised by the site of application: skin, i.e. galenical aspects of topical compositions
A61K 9/06
Medicinal preparations characterised by special physical form: ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
A61K 31/355
3,4-Dihydrobenzopyrans, e.g. chroman, catechin: tocopherols, e.g. vitamin E