Hair growth stimulation with nitroxide and other radicals

Claim 2

A method according to claim 1, wherein applications are repeated over a sufficient period of time to stimulate hair growth.

Claim 4

A method according to claim 3, wherein the radical-forming compound and the reducing agent are separated prior to mixing, and the mixture is applied to skin within about one hour following mixing.

Claim 5

A method according to claim 3 or 4, wherein the nitroxide radical-forming compound is trinitroglycerin, amyl nitrate, erithrithymyl tetranitrate, isosorbide dinitrate, isosorbide-2-nitrate, isosorbide-5-nitrate, isomannide dinitrate, isomannide-2-nitrate, isoidide dinitrate, or isoidide-2-nitrate.

Claim 6

A method according to claim 3 or 4, wherein the nitroxide radical-forming compound is an alkali metal nitrite or transition metal nitrite.

Claim 7

A method according to claim 6, wherein the nitroxide radical-forming compound is sodium nitrite.

Claim 10

A kit for preparing a unit dosage of a hair growth stimulating preparation, comprising: a unit dosage amount of a pharmacologically acceptable nitroxide radical-forming compound selected from organic nitrates and inorganic nitrites in a pharmaceutical carrier; a unit dosage amount of a pharmacologically acceptable reducing agent in a pharmaceutical carrier, the reducing agent being reactive with the radical-forming compound to form nitroxide radicals; means for separating the unit dosage amounts from each other prior to dispensing; and means for dispensing the unit dosage amounts.

Claim 11

A kit according to claim 10, wherein the unit dosage amounts are in a total volume of about 0.5 to 1.0 ml.

Claim 12

A composition for topical stimulation of hair growth, comprising: a pharmacologically acceptable stable free radical source compound selected from nitroxide spin labels and N-oxides of niacins and pharmacologically acceptable adjuvant selected from reducing agents, antioxidants and hydroxyl radical scavengers, in association with a topical pharmaceutical carrier.

Claim 13

The composition of claim 12, wherein said source compound is present at a concentration of from 0.1 to 20 weight percent and said adjuvant is present at a concentration of from 0.1 to 20 weight percent.

Claim 14

The composition of claim 12 or 13, wherein said adjuvant is a hydroxyl radical scavenger having a specific reaction rate constant with hydroxyl radical of at least 5x10⁹dm³/mol-sec.

Claim 15

The composition of any of claims 12 to 14, wherein said adjuvant is a hydroxyl radical scavenger having a specific reaction rate constant with hydroxyl radical greater than that of nitric oxide.

Claim 16

The composition of any of claims 12 to 15, wherein said adjuvant is selected from dialkyl sulfoxides, tertiary phosphine oxides, retinoids, basic amino acids and basic peptides.

Claim 17

The composition of claim 12, wherein said adjuvant comprises dimethyl sulfoxide present at from about 5 to about 25 percent by weight of the composition.

Claim 18

The composition of claim 12, wherein said adjuvant comprises dimethyl sulfoxide present at from about 15 to about 20 percent by weight of the composition.

Claim 19

The composition of any of claims 12 to 15, wherein said adjuvant is selected from carotene, tretinoin, isotretinoin, 9-cis-dehydroretinol, retinal, etretinate, retinal acetate and 9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-2,4,6, 8-nonatetraenoic acid.

Claim 20

The composition of any of claims 12 to 15, wherein said adjuvant is selected from mannitol, benzoic acid, p-aminobenzoic acid, thioproline, homocystein, cysteine, acetyl cysteine, dithiothreitol, sodium dithionate, thiosalicylic acid, mercapotethanolamine, propyl gallate, hydroxyethylruticide and pantothenic acid..

Claim 21

The composition of any of claims 12 to 15, wherein said adjuvant is selected from the group consisting of basic amino acids, peptides comprised predominantly thereof, and metal complexes of said amino acids and peptides.

Claim 22

The composition of claim 21, wherein said basic amino acids are selected from glycine, histidine, lysine, arginine, cysteine, and methionine.

Claim 23

The composition of any of claims 12 to 22, further comprising from 0.01 to 5 weight percent of an antiandrogen in association with said carrier.

Claim 24

The composition of claim 23, wherein said antiandrogen is spironolactone.

Claim 25

The composition of any of claims 12 to 24, wherein said adjuvant includes a compound having SODase activity at a concentration of 0.01-10mM.

Claim 26

The composition of claim 25, wherein said SODase compound is selected from superoxide dismutase, copper aspirinate and indomethicin-copper.

Claim 27

The composition of any of claims 12 to 26, wherein said free radical source compound is selected from nicotinic acid N-oxide and nicotinamide N-oxide.

Claim 28

The composition of claims 12 to 26, wherein said free radical source compound is selected from 4,4-dimethyl-3-oxazolinyloxy ("doxyl"), 3-doxyl-5α -cholestane, 3-doxyl-17β-hydroxy-5α-androstane, 5-doxylstearic acid, 7-doxylstearic acid, 12-doxylstearic acid, 16-doxylstearic acid, 5-doxylstearic acid methyl ester, 7-doxylstearic acid methyl ester, 12-doxylstearic acid methyl ester, and 16-doxylstearic acid methyl ester.

Claim 29

The composition of any of claims 12 to 26, wherein said free radical source compound is selected from 2,2,5,5-tetramethyl-1-pyrrolidinyloxyl ("proxyl"), 3-(aminomethyl)-proxyl, 3-(2-[2-bromoacetamido]acetamido)-proxyl, 3-(2-[2-2-bromoacetamido)-ethoxyethyl]-carbamoyl)-proxyl, 3-(2-bromoacetamido]-methyl)-proxyl, 3-(3-[2-bromoacetamido]-proxyl, 3-(2-bromoacetamido]- propylcarbamoyl-proxyl, 3-(2-bromoacetamido)-proxyl, 3-carbamoyl-proxyl, 3-carboxy-proxyl, 3-cyano-proxyl, 3-(5-[dimethylamino] -1-naphthalene-sulfonamido)-proxyl, 3-(5-[dimethylamino]-1-naphthalene-sulfonamido)-proxyl, 3-(5-fluoro-2,4-dinitroanilino)-proxyl, 3-(2-[2-iodoacetamido]acetamido)-proxyl, 3-(2-[2-(-iodoacetamido)-ethoxyethyl]-carbamoyl)-proxyl, 3-(2-iodoacetamidomethyl)-proxyl, 3-(3-[2-iodoacetamido]-ethoxyethyl]-carbamoyl)-proxyl, 3-(2-iodoacetamidomethyl)-proxyl, 3-(3-[2-iodoacetamido]-propylcarbamoyl)-proxyl, 3-(2-iodoacetamido)-proxyl, 3-(2-[2-isothiocyanatoethoxy]-ethylcarbamoyl]-proxyl, 3-(2-isothiocyanatoethylcarbamoyl)-proxyl, 3-(isothiocyanatomethyl)-proxyl, 3-(2-[2-maleimidoethoxy]-ethylcarbamoyl)-proxyl, 3-(2-maleimidoethyl-carbamoyl)-3-(3-maleimidopropylcarbamoyl)-proxyl, 3-maleimidoproxyl, 3-(4-nitrophenoxy carbonyl)-proxyl, and N,N'-bis(3-proxyl carbonyl)-1,2- ethanediamine.

Claim 30

The composition of any of claims 12 to 26, wherein asad free radical source compound is selected from 2,2,6,6-tetramethyl-1-piperidinyloxyl ("tempo"), 4-amino-tempo, 4-(2-bromoacetamido)-tempo, 4-[N-formyl-N-(3-hydroxypropyl)amino]-tempo, 4-[N,N-bis-(2-hydroxyethyl)amino-tempo, 4-(ethoxyfluorophosphinyloxy)-tempo, 4-hydroxy-tempo, 4-(2-iodoacetamido)-tempo, 4-isothiocyanato-tempo, 4-maleimido-tempo, 4-(4-nitrobenzoyloxy)-tempo, 4-oxo-tempo, 4-phosphonooxy-tempo, N,N'bis(4-tempo)-oxamide, 1,2-ethanediaminietetraacetic acid, 2',4'-bis[(CN-4-tempo)amide], N,N'-bis(4-tempo)-1,2-ethanediamine, and N,N'-bis(4-tempo)decanediamide.

Claim 31

The composition of any of claims 12 to 26, wherein said free radical source compound is selected from 2-(acetoxymercuri)-4,4,4-tetramethyl-2-imidazolin-1-yloxy-3-oxide, 3-carbamoyl-2,5-dihydro-2,2,5,5-tetramethyl-1H-pyrrol-1-yloxy, and 3,([ethoxycarbonyl]-oxycarbonyl)-2,5-dihydro-2,2,5,5-tetramethyl-1H-pyrrol-1-yloxy.

Claim 32

The composition of any of claims 12 to 26, wherein said free radical source compound is selected from melanin; N-t-butyl-α-phenyl-nitrone, 3,5-dibromo-4-nitroso-benzenesulfonic acid, 5,5-dimetnyl-1-pyrroline N-oxide, 2-methyl-2-nitroso-propane, nitrosobenzene, nitrosodisulfonic acid, α-(4-pyridyl-1-oxide)-N-t-butylnitrone, 3,3,5,5-tetramethyl-pyrroline N-oxide, and 2,4,6-tri-t-butylnitrosobenzene.

Claim 33

The composition of any of claims 12 to 32, wherein the adjuvant is selected from acetyl cystein and suitable pharmacologically acceptable compounds which have substantial reactivity with hydroxyl radicals, such as those listed in Ross and Ross, "Selected Specific Rates of Reactions of Transients from Water in Aqueous Solution. III. Hydroxyl Radical and Perhydroxyl Radicals and Their Radical Ions", National Standard Reference Data Series, National Bureau of Standards, 59 (1977),

Claim 34

A method for stimulating hair growth for cosmetic treatment, comprising repeatedly topically applying to the skin a composition as claimed in claim 33 at a concentration and over a period of time sufficient to stimulate hair growth from the skin.