WO1988000040A1 - Topical hair growing composition and kit - Google Patents

Topical hair growing composition and kit Download PDF

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Publication number
WO1988000040A1
WO1988000040A1 PCT/US1987/001575 US8701575W WO8800040A1 WO 1988000040 A1 WO1988000040 A1 WO 1988000040A1 US 8701575 W US8701575 W US 8701575W WO 8800040 A1 WO8800040 A1 WO 8800040A1
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WO
WIPO (PCT)
Prior art keywords
sulfonamide
compound
dioxide
benzothiadiazine
chloro
Prior art date
Application number
PCT/US1987/001575
Other languages
French (fr)
Inventor
Phillip Frost
Jack Fishman
Original Assignee
American Health Products Corporation
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Filing date
Publication date
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Publication of WO1988000040A1 publication Critical patent/WO1988000040A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • A61K8/492—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • a method of enhancing growth of fine vellous hair into terminal hair in an least partially bald person which comprises topically applying to the scalp a compound selected from the group consisting of 6-chloro-3,4-dih ⁇ dro-2H-l,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide, 6-chloro-3- ( dichloromethyl ) -3 , 4-dihydro-2H-l , 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide, 2-chloro-5-( l-h ⁇ droxy-3-oxo-l- isoindolinyl )benzene sulfonamide, 3 , 4-dihydro-3-(phenyl- methyl ) -6- ( trifluoromethyl ) -2H-1 , 2, 4-benzothiadiazine-7-
  • the method provides permitting the normal growth of fine vellous hair into terminal hair.
  • the total amount of said compound applied each day to the scalp of the patient will vary dependent upon the individual patient. It is contemplated that said compound is administered at least once per day, with one embodiment being twice per day application. The concentration of said compound is also not critical as it is the total amount of said compound that is important.
  • the suitable solvent serves to place said compound in contact with the bald area, so that ultimately there is only the said compound acting directly on the site to the effected. Because the dosage is topical, essentially 100% of said compound is in direct contact with the area to be treated, so that very low dosages can be used.
  • the individual dosage will be from about 0.5 to about 2 cc, once or twice per day, at any of the concentration ranges-
  • a topical solution containing at least about 0.01 weight percent said compound in a suitable carrier for said compound.
  • the total amount of said compound in the suitable carrier may vary greatly, it being understood that it is the total dosage of said compound that is important, and not the total amount of the total solution.
  • a more dilute solution is preferred so that a larger total volume of fluid is applied to the scalp.
  • the maximum amount of said compound is widely varied and said compound may be present up to the saturation point in the suitable solvent.
  • One preferred embodiment is the provision of at least about 0.01% said compound.
  • said suitable carrier is propylene glycol.
  • said suitable carrier is an ethanolic solution.
  • a topical medication for reversing the effects of baldness on the scalp of an at least partially bald subject which comprises a baldness-reversing amount of said compound in a form suitable for topical administration in a carrier therefor, said compound upon continued application to said scalp effecting the growth of hair thereon.
  • said compound is in one embodiment present in an amount of at least about 0.01 weight percent said compound in said suitable carrier for said compound.
  • a method for reversing the effects of baldness on the scalp of an at least partially bald subject which comprises administering topically to said scalp a baldness-reversing amount of said compound, said compound upon continued application to said scalp effecting the growth of hair thereon.
  • said compound is applied from a topical solution containing at least about 0.01 weight percent compound in a suitable carrier for said compound.
  • kits containing a medication suitable for reversing the effects of baldness on the scalp of an at least partially bald subject which comprises a package containing: (a) a container including said compound in a form suitable for topical adminis ⁇ tration to the scalp of said subject; and (b) directions for administration of said compound to said scalp for the reversal of the effects of baldness said compound upon continued application to said scalp effecting the growth of hair thereon.
  • the container may be a standard pharmaceutical container such as a bottle with label directions attached directly to the bottle which explain that said compound which is the active ingredient of the present kit, topical medication and method, is to be topically administered to the scalp of an at least partially bald patient wishing to have hair growth in the bald areas of his scalp.
  • the container may be a box or other cardboard, plastic or similar container having therein both a package insert with instructions on how to use said compound as a topical baldness treatment together with an inner container of said compound in a suitable solvent therefor.
  • Baldness generally is due to the failure of the hairs to be permitted to grow into terminal hairs, the large "hair” as laymen understand that term to be. Instead, the fine vellous hair that normally would grow into the terminal hair is essentially precluded from such growth.
  • Said compound acts in the following manner. The smooth muscles in the small blood vessels in the papilla part of connective tissue of skin that supplies the hair follicle are relaxed, thereby increasing blood flow to the hair matrix leading to the maturation -of fine hairs into terminal hairs. As a result, there is permitted the maturation of the fine hairs into terminal hairs as would be the case in a normal person without baldness.
  • 6-chloro-3,4-dihydro-2H-l,2,4-benzothiadia- zine-7-sulfonamide 1,1-dioxide is known as a diuretic agent, but never as a topical medication.
  • 6-chloro-3,4-dihydro- 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide any derivatives and salt forms of 6-chloro- 3,4-dihydro-2H-l,2, -benzothiadiazine-7-sulfonamide 1,1- dioxide are also contemplated within the scope of the invention and may be used instead of the 6-chloro-3, 4-dihydro- 2H-1, 2,4-benzothiadiazine-7-sulfonamide 1, 1-dioxide.
  • an ethanolic solution is contemplated as a preferred embodiment.
  • active ingredient refers to the compound 6-chloro-3, 4-dihydro-2H-l , 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide. Trial no. Active Ingredient Placebo 1 1 3 2 1 2 3 2 2 4 3 2 5 1 1 6 3 1
  • a standard bottle for pharmaceutical liquids is filled with 200 ml of the solution of this example, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 6-chloro- 3,4 ⁇ dih ⁇ dro-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1- dioxide for alleviation of the effects of baldness.
  • a propylene glycol solution is prepared with 6-chloro- 3,4-dihydro-2H-l,2, 4-benzothiadiazine-7-sulfonamide 1,1- dioxide in place of the 5% ethanolic solution previously described.
  • 6-chloro-3-(dichloro- methyl)-3,4-dihydro-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide It is to be understood that derivatives and salt forms of 6-chloro-3-(dichloromethyl)-3,4-dih ⁇ dro-2H-l,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide are also contemplated within the scope of the invention and may be used instead of the 6-chloro-3-(dichloromethyl)-3,4-dihydro-2H- 1, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide.
  • the compound 6-chloro-3-( dichloromethyl )-3, -dihydro-2H-l, 2, 4- benzothiadiazine-7-sulfonamide 1,1-dioxide is disclosed in deStevens et al., Experientia, 16, 113 (1960).
  • the compound has a solubility in water of 0.8 rag/ml at 25 °C, and a solubility in ethanol of 21 mg/ml at 25°C.
  • active ingredient refers to the compound 6-chloro-3-(dichloro ⁇ methyl)-3,4-dihydro-2H-l,2,4-benzpthiadiazine-7-sulfonamide 1,1-dioxide. Trial no. Active Ingredient Placebo
  • a propylene glycol solution is prepared with 6-chloro-3- (dichloromethyl)-3,4-dihydro-2H-l,2,4-benzothiadiazine-7- sulfonamide 1,1-dioxide in place of the previously described 5% ethanolic solution.
  • an ethanolic solution is contemplated as a preferred embodiment.
  • the resultant solution contains a two percent 2-chloro-5-(l- hydroxy-3-oxo-l-isoindolinyl )benzene sulfonamide - in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness.
  • a standard bottle for pharmaceutical liquids is filled with 200 ml of the solution of this example, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 2-chloro- 5- ( l-hydroxy-3-oxo-l-isoindolinyl )benzene sulfonamide for alleviation of the effects of baldness.
  • a propylene glycol solution is prepared with 2-chloro-5- (l-hydroxy-3-oxo-l- " isoindolinyl)benzene sulfonamide in place of the 5% ethanolic solution.
  • the compound is not soluble in water but is soluble in alcohols, making an ethanolic solution a preferred embodiment of the present invention.
  • the resultant solution contains a two percent 3, 4-dihydro-3-( henylmethyl )- 6-( trifluoromethyl )-2H-l, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness.
  • a standard bottle for pharmaceutical liquids is filled with 200 ml of the solution and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 3,4-dihydro-3- (phenylmethyl )-6-( trifluoromethyl )-2H-l, 2, 4-benzothiadiazine- 7-sulfonamide 1,1-dioxide for alleviation of the effects of baldness.
  • active ingredient refers to the compound 3 , 4-dihydro-3- (phenylmethyl ) -6- (trifluoromethyl)-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1- dioxide.
  • a propylene glycol solution is prepared with 3,4-dihydro- 3-(phenylmethyl )-6-(trifluoromethyl )-2H-1,2,4-benzothiadia- zine-7-sulfonamide 1,1-dioxide in place of the 95% ethanolic solution.
  • any derivatives and salt forms of 6-chloro-3-(chloromethyl )-3, 4- dihydro-2-methyl-2H-l, 2, 4-benzothiadiazine-7-sulfonamide 1, 1- dioxide are also contemplated within the scope of the invention and may be used instead of the 6-chl.oro-3-(chloro- methyl )-3, 4-dihydro-2-meth l yl: ⁇ 2H-l , 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide.
  • active ingredient refers to the compound 6-chloro-3-(chloromethyl)-3,4-dihydro- 2-methyl-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Trial no. Active Ingredient Placebo
  • a propylene glycol solution is prepared with 6-chloro-3- ( chloromethyl ) -3 , 4-dihydro-2-methyl-2H-l., 2 , 4-benzothiadiazine- 7 -sul f onamide 1 , 1 -dioxide in pl ace of the 5% ethanolic solution.
  • the resultant solution contains a two percent 6-chloro-3,4- dihydro-2-methyl-3- [(2,2,2-trifluoroethyl)thio]methyl ⁇ -2H- 1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness.
  • a standard bottle for pharmaceutical liquids is filled with 200 ml of the solution of this example, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 6-chloro- 3,4-dihydr ⁇ -2-methyl-3- ⁇ [(2,2,2-trifluoroethyI)thio]methyl ⁇ - 2H-1, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide for alleviation of the effects of baldness.
  • a propylene glycol solution is prepared with 6-chloro- 3,4-dihydro-2-methyl-3- ⁇ [(2,2,2-trifluoroethyl)thio]methyl ⁇ - 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide in place of the 95% ethanolic solution.
  • 6-chloro-2H-l 2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide. It is to be understood that any derivatives and salt forms of 6-chloro-2H- 1, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide are also contemplated within the scope of the invention and may be used instead of the 6-chloro-2H-l , 2 , 4-benzothiadiazine-7- sulfonamide 1, 1-dioxide.
  • an ethanolic solution is contemplated as a preferred embodiment.
  • a standard bottle for pharmaceutical liquids is filled with 200 ml of the solution of this example, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 6-chloro- 2H-1 , 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide for alleviation of the effects of baldness.
  • the compound 6-chloro-2H-l , 2 , 4-benzothiadiazine-7- sulfonamide 1,1-dioxide was tested for treating baldness.
  • the resultant solution contains a two percent 3,4-dihydro-6-trifluoromethyl- 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness.
  • a standard bottle for pharmaceutical liquids is filled with 200 ml of the solution of this example, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 3,4- dihydro-6-trifluoromethyl-2H-1, 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide for alleviation of the effects of baldness.
  • active ingredient refers to the compound 3,4-dihydro-6-trifluoromethyl-2H-1,2,4-benzothia- diazine-7-sulfonamide 1,1-dioxide Trial no. Active Ingredient Placebo
  • a propylene glycol solution is prepared with 3,4-dihydro- 6-trifluoromethyl-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1- dioxide in place of the 95% ethanolic solution.

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Abstract

A method for enhancing growth of fine vellous hair into terminal hair in an at least partially bald person which comprises topically applying to the scalp a compound selected from the group consisting of 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, 6-chloro-3-(dichloromethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, 2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl)benzene sulfonamide, 3,4-dihydro-3-(phenylmethyl)-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, 6-chloro-3-(chloromethyl)-3,4-dihydro-2-methyl-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, 6-chloro-3,4-dihydro-2-methyl-3-{[(2,2,2-trifluoroethyl)thio]methyl}-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide and 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide whereby the smooth muscles in the small blood vessels in the papilla part of connective tissue of skin that supplies the hair follicle is relaxed, thereby increasing blood flow to the hair matrix leading to the maturation of fine hairs into terminal hairs. Also provided is a topical medication and method for reversing the effects of baldness focused upon said compound as the active ingredient. A kit is provided which comprises the medication with said compound suitable for reversing the effects of baldness on the scalp of an at least partially bald subject which comprises a package including said compound and directions for administration of said compound to said scalp for the reversal of the effects of baldness.

Description

_Top cai hai ? growing composition and i . In accordance with a first aspect of the invention there is provided A method of enhancing growth of fine vellous hair into terminal hair in an least partially bald person which comprises topically applying to the scalp a compound selected from the group consisting of 6-chloro-3,4-dihγdro-2H-l,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide, 6-chloro-3- ( dichloromethyl ) -3 , 4-dihydro-2H-l , 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide, 2-chloro-5-( l-hγdroxy-3-oxo-l- isoindolinyl )benzene sulfonamide, 3 , 4-dihydro-3-(phenyl- methyl ) -6- ( trifluoromethyl ) -2H-1 , 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide, 6-chloro-3-( chloromethyl )-3, 4- dihydro-2-methγl-2Hrl,2,4-benzothiadiazine-7-sulfonamide 1, 1- dioxide, 6-chloro-3, 4-dihγdro-2-methyl-3-{ [(2,2, 2-trifluoro- ethyl )thio]methyl}-2H-l, 2,4-benzothiadiazine-7-sulfonamide 1, 1-dioxide, 6-chloro-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide and 3,4-dihydro-6-trifluoromethyl-2H-l,2,4-benzo- thiadiazine-7-sulfonamide 1,1-dioxide whereby the smooth muscles in the small blood vessels in the papilla part of connective tissue of skin that supplies the hair follicle is relaxed, thereby increasing blood flow to the hair matrix leading to the maturation of fine hairs into terminal hairs. Thus, the method provides permitting the normal growth of fine vellous hair into terminal hair. According to this aspect of the invention, in one embodiment there is provided a method of permitting the normal growth of fine vellous hair into terminal hair in an least partially bald person in accordance with claim 1, wherein said compound is applied from a topical solution containing at least about 0.01 weight percent said compound in a suitable carrier for said compound.
The total amount of said compound applied each day to the scalp of the patient will vary dependent upon the individual patient. It is contemplated that said compound is administered at least once per day, with one embodiment being twice per day application. The concentration of said compound is also not critical as it is the total amount of said compound that is important. The suitable solvent serves to place said compound in contact with the bald area, so that ultimately there is only the said compound acting directly on the site to the effected. Because the dosage is topical, essentially 100% of said compound is in direct contact with the area to be treated, so that very low dosages can be used.
In a preferred embodiment the individual dosage will be from about 0.5 to about 2 cc, once or twice per day, at any of the concentration ranges-
In one embodiment of this first aspect of the present invention there is provided a topical solution containing at least about 0.01 weight percent said compound in a suitable carrier for said compound. The total amount of said compound in the suitable carrier may vary greatly, it being understood that it is the total dosage of said compound that is important, and not the total amount of the total solution. To the extent that it is desired not to have too great an amount of said compound applied to any one spot on the scalp, a more dilute solution is preferred so that a larger total volume of fluid is applied to the scalp. The maximum amount of said compound is widely varied and said compound may be present up to the saturation point in the suitable solvent. One preferred embodiment is the provision of at least about 0.01% said compound.
In a preferred embodiment of this first aspect of the present invention, said suitable carrier is propylene glycol. In yet another preferred embodiment, said suitable carrier is an ethanolic solution. In a second aspect of the present invention, there is provided a topical medication for reversing the effects of baldness on the scalp of an at least partially bald subject which comprises a baldness-reversing amount of said compound in a form suitable for topical administration in a carrier therefor, said compound upon continued application to said scalp effecting the growth of hair thereon. In said topical medication said compound is in one embodiment present in an amount of at least about 0.01 weight percent said compound in said suitable carrier for said compound.
In a third aspect of the present invention there is provided a method for reversing the effects of baldness on the scalp of an at least partially bald subject which comprises administering topically to said scalp a baldness-reversing amount of said compound, said compound upon continued application to said scalp effecting the growth of hair thereon. In a preferred embodiment of said method, said compound is applied from a topical solution containing at least about 0.01 weight percent compound in a suitable carrier for said compound.
In a fourth aspect of the present invention there is provided a kit containing a medication suitable for reversing the effects of baldness on the scalp of an at least partially bald subject which comprises a package containing: (a) a container including said compound in a form suitable for topical adminis¬ tration to the scalp of said subject; and (b) directions for administration of said compound to said scalp for the reversal of the effects of baldness said compound upon continued application to said scalp effecting the growth of hair thereon. The container may be a standard pharmaceutical container such as a bottle with label directions attached directly to the bottle which explain that said compound which is the active ingredient of the present kit, topical medication and method, is to be topically administered to the scalp of an at least partially bald patient wishing to have hair growth in the bald areas of his scalp. Alternatively, the container may be a box or other cardboard, plastic or similar container having therein both a package insert with instructions on how to use said compound as a topical baldness treatment together with an inner container of said compound in a suitable solvent therefor.
Baldness generally is due to the failure of the hairs to be permitted to grow into terminal hairs, the large "hair" as laymen understand that term to be. Instead, the fine vellous hair that normally would grow into the terminal hair is essentially precluded from such growth. Said compound acts in the following manner. The smooth muscles in the small blood vessels in the papilla part of connective tissue of skin that supplies the hair follicle are relaxed, thereby increasing blood flow to the hair matrix leading to the maturation -of fine hairs into terminal hairs. As a result, there is permitted the maturation of the fine hairs into terminal hairs as would be the case in a normal person without baldness.
EXAMPLE I The compound 6-chloro-3, 4-dihydro-2H-l,2,4-benzothia- diazine-7-sulf onamide 1,1-dioxide is described in the literature, including Downing, U.S. patent 3,043,840 (1962), Irons et al., U.S. patent 3,164,588 (1965), de Stevens et al, U.S. patent 3,163,645 (1964), and Jones et al., U.S. patent 3,025,292.
The use of 6-chloro-3,4-dihydro-2H-l,2,4-benzothiadia- zine-7-sulfonamide 1,1-dioxide is known as a diuretic agent, but never as a topical medication.
Reference has been made herein to 6-chloro-3,4-dihydro- 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. It is to be understood that any derivatives and salt forms of 6-chloro- 3,4-dihydro-2H-l,2, -benzothiadiazine-7-sulfonamide 1,1- dioxide are also contemplated within the scope of the invention and may be used instead of the 6-chloro-3, 4-dihydro- 2H-1, 2,4-benzothiadiazine-7-sulfonamide 1, 1-dioxide.
As this compound has limited solubility in water but has solubility in ethanol, an ethanolic solution is contemplated as a preferred embodiment.
To a graduated 1000 ml beaker there are added first 20 mg powdered 6-chloro-3, 4-dihydro-2H-l, 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide and 55 ml 95% ethanol which are intimately mixed together, followed by addition of water to the 1000 ml mark. The resultant solution contains a two percent 6-chloro-3, 4-dihydro-2H-l, 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness. For the treatment of baldness, on a daily basis there is administered 2 cc to the scalp of said patient for the growth of hair on said bald spot. Administration is carried on twice a day, once in the morning after showering and once in the evening before retiring. The compound 6-chloro-3, 4-dihydro-2H-l , 2, 4-benzothia- diazine-7-sulfonamide 1,1-dioxide was tested for treating baldness. To test the suitability of 6-chloro-3, 4-dihydro-2H- 1 , 2 , 4-benzothiadiazine-7-sulfonamide 1,1-dioxide as a treatment agent for baldness the following test was conducted. A total of 12 mouse trials were involved. A test was made for 6-chloro-3, 4-dihydro-2H-l, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide on hairless weanling mice on a grading scale of no hair growth ("0"); sparse growth ("1"); fuzzy growth ("2"); and very fuzzy growth ("3"). Six different mice were tested for the compound 6-chloro-3, 4-dihydro-2H-l, 2, 4-benzothia- diazine-7-sulfonamide 1,1-dioxide versus six placebo trials. In the following tabulation, "active ingredient" refers to the compound 6-chloro-3, 4-dihydro-2H-l , 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide. Trial no. Active Ingredient Placebo 1 1 3 2 1 2 3 2 2 4 3 2 5 1 1 6 3 1
With the placebo having only one trial hitting the 3 level and two with the 1 level, the trials for 6-chloro-3,4- dihydro-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide show a superior result for the compound of this example versus the placebo.
A standard bottle for pharmaceutical liquids is filled with 200 ml of the solution of this example,, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 6-chloro- 3,4~dihγdro-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1- dioxide for alleviation of the effects of baldness.
A propylene glycol solution is prepared with 6-chloro- 3,4-dihydro-2H-l,2, 4-benzothiadiazine-7-sulfonamide 1,1- dioxide in place of the 5% ethanolic solution previously described.
EXAMPLE II The use of 6-chloro-3-(dichloromethyl)-3,4-dihydro-2H- 1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide is known as a diuretic and antihypertensive agent, but never as a topical medication.
Reference has been made herein to 6-chloro-3-(dichloro- methyl)-3,4-dihydro-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. It is to be understood that derivatives and salt forms of 6-chloro-3-(dichloromethyl)-3,4-dihγdro-2H-l,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide are also contemplated within the scope of the invention and may be used instead of the 6-chloro-3-(dichloromethyl)-3,4-dihydro-2H- 1, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide. The compound 6-chloro-3-( dichloromethyl )-3, -dihydro-2H-l, 2, 4- benzothiadiazine-7-sulfonamide 1,1-dioxide is disclosed in deStevens et al., Experientia, 16, 113 (1960). The compound has a solubility in water of 0.8 rag/ml at 25 °C, and a solubility in ethanol of 21 mg/ml at 25°C.
To a graduated 1000 ml beaker there are added first 20 mg powdered 6-chloro-3-( dichloromethyl )-3, 4-dihydro-2H-l, 2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide and 55 ml 95% ethanol which are intimately mixed together, followed by addition of water to the 1000 ml mark. The resultant solution contains a two percent 6-chloro-3-(dichloromethyl )- 3 , 4-dihydro-2H-l , 2 , 4-benzothiadiazine-7-sulfonamide 1,1- dioxide in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness.
For the treatment of baldness, on a daily basis there is administered 2 cc to the scalp of said patient for the growth of hair on said bald spot. Administration is carried on twice a day, once in the morning after showering and once in the evening before retiring.
50 mg..6-chloro-3-( ichloromethyl )-3,4-dihydro-2H-l, 2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide is dissolved in 1000 ml water to provide a solution for use in treatment of baldness. A standard bottle for pharmaceutical liquids is filled with 200 ml of the solution of this example, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 6- chloro-3-(dichloromethyl )-3,4-dihydro-2H-l, 2, 4-benzothiadia- zine-7-sulfonamide 1,1-dioxide for alleviation of the effects of baldness.
The compound 6-chloro-3-(dichloromethyl)-3,4-dihydro-2H- 1, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide was tested for treating baldness. To test the suitability of 6-chloro-3- (dichloromethyl )-3,4-dihydro-2H-l, 2,4-benzothiadiazine-7- sulfonamide 1,1-dioxide as a treatment agent for baldness the following test was conducted. A total of 12 mouse trials were involved. A test was made for 6-chloro-3-(dichloromethyl)- 3,4-dihydro-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1- dioxide on hairless weanling mice on a grading scale of no hair growth ("0"); sparse growth ("1"); fuzzy growth ("2"); and very fuzzy growth ("3"). Six different mice were tested for the compound 6-chloro-3-(dichloromethyl)-3,4-dihydro-2H- 1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide versus six placebo trials. In the following tabulation, "active ingredient" refers to the compound 6-chloro-3-(dichloro¬ methyl)-3,4-dihydro-2H-l,2,4-benzpthiadiazine-7-sulfonamide 1,1-dioxide. Trial no. Active Ingredient Placebo
1 1 3
2 1 2
3 3 2
4 3 2 5 1 1
6 1 1
"With" the placebo having only one trial hitting the 3 level and two with the 1 level, the trials for 6-chloro-3-
(dichloromethyl)-3, -dihydro-2H-l, 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide show a superior result for the compound of this example versus the placebo.
A propylene glycol solution is prepared with 6-chloro-3- (dichloromethyl)-3,4-dihydro-2H-l,2,4-benzothiadiazine-7- sulfonamide 1,1-dioxide in place of the previously described 5% ethanolic solution.
EXAMPLE III The compound 2-chloro-5-(l-hydroxy-3-oxo-l-isoindol- inyl)benzene sulfonamide is described in the literature. Reference has been made herein to 2-chloro-5-(l-hydroxy-3-oxo- 1-isoindolinyl )benzene sulfonamide. It is to be understood that any derivatives and salt forms of 2-chloro-5-( 1-hydroxy- 3-oxo-l-isoindolinyl)benzene sulfonamide are also contemplated within the scope of the invention and may be used instead of the 2-chloro-5- ( l-hydroxγ-3-oxo-l-isoindolinyl )benzene sulfonamide.
As this compound has limited solubility in water but has solubility in ethanol, an ethanolic solution is contemplated as a preferred embodiment. To a graduated 1000 ml beaker there are added first 20 mg powdered 2-chloro-5-( l-hydroxy-3-oxo-l-isoindolinyl )benzene sulfonamide and 55 ml 95% ethanol which are intimately mixed together, followed by addition of water to the 1000 ml mark. The resultant solution contains a two percent 2-chloro-5-(l- hydroxy-3-oxo-l-isoindolinyl )benzene sulfonamide - in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness.
For the treatment of baldness, on a daily basis there is administered 2 cc to the scalp of said patient for the growth of hair on said bald spot. Administration is carried on twice a day, once in the morning after showering and once in the evening before retiring.
A standard bottle for pharmaceutical liquids is filled with 200 ml of the solution of this example, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 2-chloro- 5- ( l-hydroxy-3-oxo-l-isoindolinyl )benzene sulfonamide for alleviation of the effects of baldness.
The compound 2-chloro-5-( l-hγdroxy-3-oxo-l-isoindol- inyl)benzene sulfonamide was tested for treating baldness. To test the suitability of 2-chloro-5- ( l-hydroxy-3-oxo-l- isoindolinyl )benzene sulfonamide as a treatment agent for baldness the following test was conducted. A total of 12 mouse trials were involved. A test was made for 2-chloro-5- ( l-hydroxy-3-oxo-l-isoindolinyl )benzene sulfonamide on hairless weanling mice on a grading scale of no hair growth ("0"); sparse growth ("1"); fuzzy growth ("2"); and very fuzzy growth ("3"). Six different mice were tested for the compound 2-chloro-5-(l-hydroxy-3-oxo-l-isoindolinyl)benzene sulfonamide versus six placebo trials. In the following tabulation, "active ingredient" refers to the compound 2-chloro-5-(l- hydroxy-3-oxo-l-isoindolinyl)benzene sulfonamide. Trial no. Active Ingredient Placebo 1 3 3
2 1 2
3 2 2
4 3 2
5 1 1 6 3 - 1
With the placebo having only one trial hitting the 3 level and two with the 1 level, the trials for 2-chloro-5-(l- hydroxy-3-oxo-l-isoindolinyl )benzene sulfonamide show a superior result for the compound of this example versus the placebo.
A propylene glycol solution is prepared with 2-chloro-5- (l-hydroxy-3-oxo-l-"isoindolinyl)benzene sulfonamide in place of the 5% ethanolic solution.
EXAMPLE IV Synthesis of 3,4-dihydro-3-(phenylmethyl)-6-(trifluoro- methyl)-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide is disclosed in Holdrege et al., J. Am. Chem. Soc, 81, 4807 (1959); and Goldberg, U.S. patent 3,265,573 (1966).
The use of 3, 4-dihydro-3-(phenylmethyl)-6-(trifluoro- methyl)-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide is known as a diuretic and antihypertensive agent, but never as a topical medication.
Reference has been made herein to 3,4-dihydro-3-(phenyl- methyl ) -6- ( trifluoromethy1 )-2H-l, 2 , 4-benzothia iazine-7- sulfonamide 1,1-dioxide. It is to be understood that derivatives and salt forms of 3, 4-dihydro-3-(phenylmethyl)-6- (trifluoromethyl)-2H-l, 2,4-benzothiadiazine-7-sulfonamide 1, 1- dioxide are also contemplated within the scope of the invention and may be used instead of the 3, 4-dihydro-3- (phenylmethyl )-6-(trifluoromethyl)-2H-l, 2, 4-benzothiadiazine- 7-sulfonamide 1, 1-dioxide.
The compound is not soluble in water but is soluble in alcohols, making an ethanolic solution a preferred embodiment of the present invention.
To a graduated 1000 ml beaker there are added first 20 mg powdered 3, 4-dihydro-3-(phenylmethyl )-6-(trifluoromethyl )-2H- 1, 2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide and 55 ml 95% ethanol which are intimately mixed together, followed by addition of water to the 1000 ml mark. The resultant solution contains a two percent 3, 4-dihydro-3-( henylmethyl )- 6-( trifluoromethyl )-2H-l, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness.
For the treatment of baldness, on/a daily basis there is administered 2 cc to the scalp of said patient for the growth of hair on said bald spot. Administration is carried on twice a day, once in the morning after showering and once in the evening before retiring.
A standard bottle for pharmaceutical liquids is filled with 200 ml of the solution and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 3,4-dihydro-3- (phenylmethyl )-6-( trifluoromethyl )-2H-l, 2, 4-benzothiadiazine- 7-sulfonamide 1,1-dioxide for alleviation of the effects of baldness.
The compound 3, 4-dihydro-3-(phenylmethyl )-6-(trifluoro¬ methyl ) -2H-1, 2, 4-benzothiadiazine-7-sulfonamide 1, 1-dioxide was tested for treating baldness. To test the suitability of 3 , 4-dihγdro-3- ( phenylmethyl ) -6- ( trif luoromethyl ) -2H-1 , 2 , 4- benzothiadiazine-7-sulfonamide 1,1-dioxide as a treatment agent for baldness the following test was conducted. A total of 12 mouse trials were involved. A test was made for 3,4- dihydro-3-( phenylmethyl ) -6-( trif luoromethyl ) -2H-1, 2,4- benzothiadiazine-7-sulf onamide 1,1-dioxide on hairless weanling mice on a grading scale of no .hair growth ("0"); sparse growth ("1"); fuzzy growth ("2"); and very fuzzy growth ("3"). Six different mice were tested for the compound 3,4- dihydro-3- (phenylmethyl ) -6-( trif luoromethyl ) -2H-1, 2, 4- benzothiadiazine-7-sulfonamide 1,1-dioxide versus six placebo trials. In the following tabulation, "active ingredient" refers to the compound 3 , 4-dihydro-3- (phenylmethyl ) -6- (trifluoromethyl)-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1- dioxide.
Trial no. Active Ingredient Placebo
1 3 3
2 1 2 3 1 2
4 1 2
5 3 1
6 3 . 1
With the placebo having only one trial hitting the 3 level and two with the 1 level, the trials for 3,4-dihydro-3-
(phenylmethyl)-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-
7-sulfonamide 1,1-dioxide show a superior result for the compound of this example versus the placebo.
A propylene glycol solution is prepared with 3,4-dihydro- 3-(phenylmethyl )-6-(trifluoromethyl )-2H-1,2,4-benzothiadia- zine-7-sulfonamide 1,1-dioxide in place of the 95% ethanolic solution.
EXAMPLE V Synthesis of 6-chloro-3-( chloromethyl )-3,4-dihydro-2- methyl-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide is disclosed in Close et al., J. Am. Chem. Soc, 82, 1132 (1960). The use of 6-chloro-3-(chloromethyl )-3,4-dihydro-2-methyl-2H- 1,2, -benzothiadiazine-7-sulfonamide 1,1-dioxide is known as a diuretic and antihypertensive agent, but never as a topical medication.
Reference has been made herein to 6-chloro-3-(chloro¬ methyl ) -3 , 4-dihydro-2-methyl-2H-l , 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide. It is to be understood that any derivatives and salt forms of 6-chloro-3-(chloromethyl )-3, 4- dihydro-2-methyl-2H-l, 2, 4-benzothiadiazine-7-sulfonamide 1, 1- dioxide are also contemplated within the scope of the invention and may be used instead of the 6-chl.oro-3-(chloro- methyl )-3, 4-dihydro-2-methlyl:^2H-l , 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide.
The compound 6-chloro-3-( chloromethyl )-3,4-dihydro-2- methyl-2H-l, 2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide is sparingly soluble in ethanol, and almost insoluble in water. To a graduated 1000 ml beaker there are added first 20 mg powdered 6-chloro-3-(chloromethyl )-3, 4-dihγdro-2-methyl-2H- 1, 2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide and 55 ml 95% ethanol which are intimately mixed together, followed by addition of water to the 1000 ml mark., The resultant solution contains a two percent 6-chloro-3-(chloromethyl )-3,4- dihydro-2-methyl-2H-l, 2,4-benzothiadiazine-7-sulfonamide 1, 1- dioxide in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness. For the treatment of baldness, on a daily basis there is administered 2 cc to the scalp of said patient for the growth of hair on said bald spot. Administration is carried on twice a day, once in the morning after showering and once in the evening before retiring. A standard bottle for pharmaceutical liquids is filled with 200 ml of the above solution, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 6-chloro-3- (chloromethyl)-3, -dihydro-2-methyl-2H-l,2,4-benzothiadiazine- 7-sulfonamide 1,1-dioxide for alleviation of the effects of baldness.
The compound 6-chloro-3-(chloromethyl )-3,4-dihydro-2- methyl-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide was tested for treating baldness. To test the suitability of 6- chloro-3-( chloromethyl ) -3, -dihydro-2-methyl-2H-l , 2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide as a treatment agent for baldness the following test was conducted. A total of 12 mouse trials were involved. A test was made for 6- chloro-3- ( chloromethyl ) -3 , 4-dihydro-2-methyl-2H-l, 2, 4- benzothiadiazine-7-suϊfonamide 1,1-dioxide on hairless weanling mice on a grading scale of no hair growth ("0"); sparse growth ("1"); fuzzy growth ("2"); and very fuzzy growth ("3"). Six different mice were tested for the compound 6- chloro-3-( chloromethyl ) -3 , 4-dihydro-2-methyl-2H-1 , 2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide versus six placebo trials. In the following tabulation, "active ingredient" refers to the compound 6-chloro-3-(chloromethyl)-3,4-dihydro- 2-methyl-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Trial no. Active Ingredient Placebo
1 1 3
2 3 2
3 2 2
4 2 2 5 3 1
6 3 1
With the placebo having only one trial hitting the 3 level and two with the 1 level, the trials for 6-chloro-3- (chloromethyl)-3,4-dihydro-2-methyl-2H-1,2,4-benzothiadiazine- 7-sulfonamide 1 , 1-dioxide show a superior result for the compound of this example versus the placebo .
A propylene glycol solution is prepared with 6-chloro-3- ( chloromethyl ) -3 , 4-dihydro-2-methyl-2H-l., 2 , 4-benzothiadiazine- 7 -sul f onamide 1 , 1 -dioxide in pl ace of the 5% ethanolic solution.
EXAMPLE VI "
Synthesis of 6-chloro-3, 4-dihydro-2-methγl-3-{ [ ( 2, 2, 2- trifluoroethyl )thio]methyl}-2H-1, 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide is disclosed in McManus, U.S. Patent
3,009,911 (1961). The use of 6-chloro-3 , 4-dihydro-2- methyl-3-{ [(2,2, 2-trifluoroethyl )thio] methyl} -2H-1 , 2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide is known as a diuretic and antihypertensive agent, but never as a topical medication.
Reference has been made herein to 6-chloro-3,4-dihydro-2- methyl-3-{ [(2,2, 2-trifluoroethyl )thio]methyl}-2H-1 , 2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide. It is to be understood that derivatives and salt forms of 6-chloro-3,4- dihydro-2-methyl-3-{[ (2, 2, 2-trifluoroethyl )thio]methyl}-2H-
1, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide are also contemplated within the scope of the invention and may be used instead of the 6-chloro-3 , 4-dihydro-2-methyl-3-{ [ ( 2, 2, 2- trifluoroethyl )thio]methyl}-2H-l , 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide. It is desirable to include in any aqueous medium alkali metal carbanates or hydroxides because the compound 6-chloro-3, 4-dihydro-2-methyl-3-{ [ ( 2, 2, 2- trifluoroethyl )thio]methyl)-2H-1 , 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide is practically insolube in water without this adjustment.
To a graduated 1000 ml beaker there are added first 20 mg powdered 6-chloro-3, 4-dihydro-2-methyl-3-{ [(2,2, 2-trifluoro¬ ethyl )thio]methyl}-2H-l , 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide and 55 ml 95% ethanol which are intimately mixed together, followed by addition of water to the 1000 ml mark. The resultant solution contains a two percent 6-chloro-3,4- dihydro-2-methyl-3- [(2,2,2-trifluoroethyl)thio]methyl}-2H- 1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness.
For the treatment of baldness, on a daily basis there is administered 2 cc to the scalp of said patient for the growth of hair on said bald spot. Administration is carried on twice a day, once in the morning after showering and once in the evening before retiring.
50 mg 6-chloro-3,4-dihydro-2-methyl-3--[ [ (2, 2,2- trifluoroethyl )thio]methyl}-2H-1,2,4-benzothiadiazine-7- sulfonamide 1,1-dioxide is dissolved in 1000 ml water having added thereto magnesium carbonate to provide a solution for use in treatment of baldness in accordance with this example.
A standard bottle for pharmaceutical liquids is filled with 200 ml of the solution of this example, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 6-chloro- 3,4-dihydrσ-2-methyl-3-{[(2,2,2-trifluoroethyI)thio]methyl}- 2H-1, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide for alleviation of the effects of baldness.
A propylene glycol solution is prepared with 6-chloro- 3,4-dihydro-2-methyl-3-{[(2,2,2-trifluoroethyl)thio]methyl}- 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide in place of the 95% ethanolic solution.
EXAMPLE VII
The compound 6-chloro-2H-l, 2,4-benzothiadiazine-7- sulfonamide 1,1-dioxide is described in the literature, including Downing, U.S. patent 3,043,840 (1962), Irons et al.,
U.S. patent 3,164,588 (1965), de Stevens et al, U.S. patent
3,163,645 (1964), and Jones et al., U.S. patent 3,025,292. The use of 6-chloro-2H-l , 2 , 4-benzothiadiazine-7- sulfonamide 1,1-dioxide is known as a diuretic agent, but never as a topical medication.
Reference has been made herein to 6-chloro-2H-l, 2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide. It is to be understood that any derivatives and salt forms of 6-chloro-2H- 1, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide are also contemplated within the scope of the invention and may be used instead of the 6-chloro-2H-l , 2 , 4-benzothiadiazine-7- sulfonamide 1, 1-dioxide.
As this compound has limited solubility in water but has solubility in ethanol, an ethanolic solution is contemplated as a preferred embodiment.
To a graduated 10Q0 ml beaker there are added first 20 mg powdered 6-chloro 2H-l,2, 4rbenzothiadiazine-7-sulfonamide 1,1- dioxide and 55 ml 95% '■ ethanol which are intimately mixed together, followed by addition of water to the 1000 ml mark. The resultant solution contains a two percent 6-chloro-2H- 1, 2, 4-benzothiadiazine-;7-sulfonamide 1,1-dioxide in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness.
For the treatment of baldness, on a daily basis there is administered 2 cc to' the scalp of said patient for the growth of hair on said bald spot. Administration is carried on twice a day, once in the- morning after showering and once in the evening before retiring.
A standard bottle for pharmaceutical liquids is filled with 200 ml of the solution of this example, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 6-chloro- 2H-1 , 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide for alleviation of the effects of baldness.
The compound 6-chloro-2H-l , 2 , 4-benzothiadiazine-7- sulfonamide 1,1-dioxide was tested for treating baldness. To test the suitability of 6-chloro-2H-l,2,4-benzothiadiazine-7- sulfonamide 1,1-dioxide as a treatment agent for baldness the following test was conducted. A total of 12 mouse trials were involved. A test was made for 6-chloro-2H-l,2,4-benzo- thiadiazine-7-sulfonamide 1,1-dioxide on hairless weanling mice on a grading scale of no hair growth ("0"); sparse growth ("1"); fuzzy growth ("2"); and very fuzzy growth ("3"); Six different mice were tested for the compound 6-chloro-2H-l,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide versus six placebo trials. In the following tabulation, "active ingredient" refers to the compound 6-chloro-2H-l,2,4-benzothiadiazine-7- sulfonamide 1,1-dioxide.
Trial no. Active Ingredient Placebo
1 2 3 2 2 2
3 . 2 2
4 3 2
5 1 1
6 3 1 With the placebo having only one trial hitting the 3 level and two with the 1 level, the trials for 6-chloro-2H- 1,2,4-benzothiadiazine-7-sul onamide 1,1-dioxide show a superior result for the compound of this example versus the placebo. A propylene glycol solution is prepared with 6-chloro-2H- 1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide in place of the 5% ethanolic solution.
EXAMPLE VIII Testing of the compound 3,4-dihydro-6-trifluoromethyl-2H- 1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide is provided in this example. To a graduated 1000 ml beaker there are added first 20 mg powdered 3,4-dihydro-6-trifluoromethyl-2H- l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide and 55 ml 95% ethanol which are intimately mixed together, followed by addition of water to the 1000 ml mark. The resultant solution contains a two percent 3,4-dihydro-6-trifluoromethyl- 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide in a 5% ethanolic solution suitable for topical application to the scalp of a bald patient for the treatment of baldness.
For the treatment of baldness, on a daily basis there is administered 2 cc to the scalp of said patient for the growth of hair on said bald spot. Administration is carried on twice a day, once in the morning after showering and once in the evening before retiring.
50 mg 3,4-dihydro-6-trifluoromethyl-2H-l,2,4-benzothia- diazine-7-sulfonamide 1,1-dioxide is dissolved in 1000 ml water having added thereto magnesium carbonate to provide a solution for use in treatment of baldness in accordance with this example.
A standard bottle for pharmaceutical liquids is filled with 200 ml of the solution of this example, and placed in a rectangular cardboard package together with a package insert giving directions for the topical administration of 3,4- dihydro-6-trifluoromethyl-2H-1, 2, 4-benzothiadiazine-7- sulfonamide 1,1-dioxide for alleviation of the effects of baldness.
The compound 3,4-dihydro-6-trifluoromethyl-2H-l, 2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide was tested for treating baldness. To test the suitability of 3,4-dihydro-6- trifluoromethyl-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1- dioxide as a treatment agent for baldness the following test was conducted. A total of 12 mouse trials were involved. A test was made for 3,4-dihydro-6-trifluoromethyl-2H-l,2,4- benzothiadiazine-7-sulfonamide 1,1.-dioxide on hairless weanling mice on a grading scale of no hair growth ("0"); sparse growth ("1"); fuzzy growth ("2"); and very fuzzy growth ("3"). Six different mice were tested for the compound 3,4- dihydro-6-trifluoromethyl-2H-l,2,4-benzothiadiazine-7- sulfonamide 1,1-dioxide versus six placebo trials. In the following tabulation, "active ingredient" refers to the compound 3,4-dihydro-6-trifluoromethyl-2H-1,2,4-benzothia- diazine-7-sulfonamide 1,1-dioxide Trial no. Active Ingredient Placebo
1 - 2 3
2 2 2
3 2 2 -
4 3 2 5 1 1
6 3 1
With the placebo having only one trial hitting the 3 level and two with the 1 level, the trials for 3,4-dihydro-6- trifluoromethyl-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1- dioxide show" a superior result for the compound of this example versus the placebo.
A propylene glycol solution is prepared with 3,4-dihydro- 6-trifluoromethyl-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1- dioxide in place of the 95% ethanolic solution.

Claims

WHAT IS CLAIMED IS:
1. A method of enhancing growth of fine vellous hair into terminal hair in an least partially bald person which comprises topically applying to the scalp a compound selected from the group consisting of 6-chloro-3,4-dihydro-2H-l,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide, 6-chloro-3-(di- chloromethyl ) -3 , 4-dihydro-2H-l , 2 , 4-benzothiadiazine-7- sulfonamide 1,1-dioxide, 2-chloro-5-( l-hγdroxy-3-oxo-l- isoindolinyl )benzene ' sulfonamide, 3, 4-dihydro-3-(phenyl- methyl ) -6- ( trifluoromethyl ) -2H-1, 2 , 4-benzothiadiazine-7- sulfonamide 1,1-dioxide, 6-chloro-3- ( chloromethyl )-3, 4- dihydro-2-methyl-2H-l,2, 4-benzothiadiazine-7-sulfonamide 1,1- dioxide, 6-αhloro-3,4-dihydro-2-methyl-3-{ [(2,2,2-trifluoro¬ ethyl )thio]methyl}-2H-l, 2, 4-benzothiadiazine-7-sulfonamide 1, 1-dioxide, 6-chloro-2H-l, 2, 4-benzothiadiazine-7-sulfonamide 1,1-dioxide and 3 , 4-dihydro-6-trifluoromethyl-2H-l, 2, 4- benzothiadiazine-7-sulfonamide 1,1-dioxide whereby the smooth muscles in the small blood vessels in the papilla part of connective tissue of skin that supplies the hair follicle is relaxed, thereby increasing blood flow to the hair matrix leading to the maturation of fine hairs into terminal hairs.
2. A method of permitting the normal growth of fine vellous hair into terminal hair in an least partially bald person in accordance with claim 1, wherein said compound is applied from a topical solution containing at least about 0.01 weight percent said compound in a suitable carrier for said compound.
3. A method of permitting the normal growth of fine vellous hair into terminal hair in an least partially bald person in accordance with claim 2, wherein said suitable carrier is propylene glycol.
4. A method of permitting the normal growth of fine vellous hair into terminal hair in an least partially bald person in accordance with claim 2, wherein said suitable carrier is an ethanolic solution.
5. A method of permitting the normal growth of fine vellous hair into terminal hair in an least partially bald person in accordance with claim 2, wherein the solvent is a mixture of ethylene glycol and propylene glycol.
6. A method of claim 1 wherein said compound is 6- chloro-3,4-dihydro-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide.
7. A method of claim 1 wherein said compound is 6- chloro-3-(dichloromethyl)-3,4-dihydro-2H-l,2,4-benzothia- diazine-7-sulfonamide 1,1-dioxide.
8. A method of claim 1 wherein said compound is 2- chloro-5-(l-hydroxy-3-oxo-l-isoindolinyl)benzene sulfonamide.
9. A method of claim 1 wherein said compound is 3,4- dihγdro-3-(phenylmethyl )-6-( trifluoromethyl )-2H-l,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide.
10. A method of claim 1 wherein said compound is 6- chloro-3-(chloromethyl)-3, 4-dihydro-2-methyl-2H-l,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide.
11. A method of claim 1 wherein said compound is 6- chloro-3, 4-dihydro-2-methy1-3- { [ (2,2,2-trifluoro¬ ethyl )thio]methyl}-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide.
12. A method of claim 1 wherein said compound is 6- chloro-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide.
13. A method of claim 1 wherein said compound is 3,4- dihydro-6-trifluoromethyl-2H-1, 2, 4-benzothiadiaz.ine-7- sulfonamide 1,1-dioxide.
14. A topical medication for reversing the effects of baldness on- the scalp of an at least partially bald subject which comprises a baldness-reversing amount of a compound of claim in a form suitable for topical administration in a carrier therefor, said compound on continued application to said scalp effecting the growth of hair thereon.
15. A topical medication of claim 14 wherein said compound is present in an amount of at least about 0.01 weight percent in said suitable carrier.
16. A method for reversing the effects of baldness on the scalp of an at least partially bald subject which comprises administering topically to said scalp a baldness- reversing amount of a compound of claim 1.
17. A kit containing a medication suitable for reversing the effects of baldness on the scalp of an at least partially bald subject which comprises a package containing:
(a) a container including a topical medication containing a compound of claim 1 for topical administration to the scalp of said subject; and (b) directions for administration of said compound to said scalp for the reversal of the effects of baldness said compound upon continued application to said scalp effecting the growth of hair thereon.
18. A kit of claim 17 wherein said compound in said container (a) includes a topical solution containing at least about 0.01 weight percent said compound in a carrier suitable therefor.
PCT/US1987/001575 1986-07-02 1987-07-02 Topical hair growing composition and kit WO1988000040A1 (en)

Applications Claiming Priority (30)

Application Number Priority Date Filing Date Title
US88123386A 1986-07-02 1986-07-02
US881,233 1986-07-02
US88367886A 1986-07-09 1986-07-09
US88368286A 1986-07-09 1986-07-09
US88368086A 1986-07-09 1986-07-09
US88367186A 1986-07-09 1986-07-09
US88367986A 1986-07-09 1986-07-09
US88368386A 1986-07-09 1986-07-09
US88368186A 1986-07-09 1986-07-09
US883,681 1986-07-09
US883,680 1986-07-09
US883,671 1986-07-09
US883,679 1986-07-09
US883,683 1986-07-09
US883,682 1986-07-09
US883,678 1986-07-09
US445587A 1987-01-20 1987-01-20
US446087A 1987-01-20 1987-01-20
US446187A 1987-01-20 1987-01-20
US446287A 1987-01-20 1987-01-20
US445987A 1987-01-20 1987-01-20
US445887A 1987-01-20 1987-01-20
US445787A 1987-01-20 1987-01-20
US004,457 1987-01-20
US004,458 1987-01-20
US004,455 1987-01-20
US004,461 1987-01-20
US004,462 1987-01-20
US004,459 1987-01-20
US004,460 1987-01-20

Publications (1)

Publication Number Publication Date
WO1988000040A1 true WO1988000040A1 (en) 1988-01-14

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PCT/US1987/001575 WO1988000040A1 (en) 1986-07-02 1987-07-02 Topical hair growing composition and kit

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Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02167213A (en) * 1988-09-09 1990-06-27 Shiseido Co Ltd Trichogen
WO1999062490A1 (en) * 1998-06-03 1999-12-09 Gpi Nil Holdings, Inc. Small molecule sulfonamide hair growth compositions and uses
WO1999062489A1 (en) * 1998-06-03 1999-12-09 Gpi Nil Holdings, Inc. N-linked sulfonamide of heterocyclic thioester hair growth compounds and uses
US6004993A (en) * 1997-06-04 1999-12-21 Gpi Nil Holdings, Inc. N-linked sulfonamide of heterocyclic thioester hair growth compounds and uses
US6172087B1 (en) 1998-06-03 2001-01-09 Gpi Nil Holding, Inc. N-oxide of heterocyclic ester, amide, thioester, or ketone hair growth compositions and uses
US6187796B1 (en) 1998-06-03 2001-02-13 Gpi Nil Holdings, Inc. Sulfone hair growth compositions and uses
US6187784B1 (en) 1998-06-03 2001-02-13 Gpi Nil Holdings, Inc. Pipecolic acid derivative hair growth compositions and uses
US6271244B1 (en) 1998-06-03 2001-08-07 Gpi Nil Holdings, Inc. N-linked urea or carbamate of heterocyclic thioester hair growth compositions and uses
US6274602B1 (en) 1998-06-03 2001-08-14 Gpi Nil Holdings, Inc. Heterocyclic thioester and ketone hair growth compositions and uses
US6274617B1 (en) 1998-06-03 2001-08-14 Gpi Nil Holdings, Inc. Heterocyclic ester and amide hair growth compositions and uses
US6331537B1 (en) 1998-06-03 2001-12-18 Gpi Nil Holdings, Inc. Carboxylic acids and carboxylic acid isosteres of N-heterocyclic compounds
US6429215B1 (en) 1998-06-03 2002-08-06 Gpi Nil Holdings, Inc. N-oxide of heterocyclic ester, amide, thioester, or ketone hair growth compositions and uses
US7078424B2 (en) 1998-06-03 2006-07-18 Gpi Nil Holdings, Inc. N-linked sulfonamides of N-heterocyclic carboxylic acids or carboxylic acid isosteres

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EP0027655A2 (en) * 1979-10-23 1981-04-29 Wella Aktiengesellschaft Use of cosmetic composition for the treatment of hair and skin of the head
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Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02167213A (en) * 1988-09-09 1990-06-27 Shiseido Co Ltd Trichogen
US6187806B1 (en) 1997-06-04 2001-02-13 Gpi Nil Holdings N-linked sulfone of heterocyclic thioester hair growth compositions and uses
US6194440B1 (en) 1997-06-04 2001-02-27 Gpi Nil Holdings, Inc. Small molecule carbamate or urea hair growth compositions and uses
US6191125B1 (en) 1997-06-04 2001-02-20 Gpi Nil Holdings, Inc. Small molecule pipecolic acid derivative hair growth compositions and uses
US6004993A (en) * 1997-06-04 1999-12-21 Gpi Nil Holdings, Inc. N-linked sulfonamide of heterocyclic thioester hair growth compounds and uses
US6177455B1 (en) 1997-06-04 2001-01-23 Gpi Nil Holdings, Inc. Pyrrolidine derivative hair growth compositions and uses
US6187784B1 (en) 1998-06-03 2001-02-13 Gpi Nil Holdings, Inc. Pipecolic acid derivative hair growth compositions and uses
US6187796B1 (en) 1998-06-03 2001-02-13 Gpi Nil Holdings, Inc. Sulfone hair growth compositions and uses
US6172087B1 (en) 1998-06-03 2001-01-09 Gpi Nil Holding, Inc. N-oxide of heterocyclic ester, amide, thioester, or ketone hair growth compositions and uses
WO1999062489A1 (en) * 1998-06-03 1999-12-09 Gpi Nil Holdings, Inc. N-linked sulfonamide of heterocyclic thioester hair growth compounds and uses
WO1999062490A1 (en) * 1998-06-03 1999-12-09 Gpi Nil Holdings, Inc. Small molecule sulfonamide hair growth compositions and uses
US6271244B1 (en) 1998-06-03 2001-08-07 Gpi Nil Holdings, Inc. N-linked urea or carbamate of heterocyclic thioester hair growth compositions and uses
US6274602B1 (en) 1998-06-03 2001-08-14 Gpi Nil Holdings, Inc. Heterocyclic thioester and ketone hair growth compositions and uses
US6274617B1 (en) 1998-06-03 2001-08-14 Gpi Nil Holdings, Inc. Heterocyclic ester and amide hair growth compositions and uses
US6331537B1 (en) 1998-06-03 2001-12-18 Gpi Nil Holdings, Inc. Carboxylic acids and carboxylic acid isosteres of N-heterocyclic compounds
US6429215B1 (en) 1998-06-03 2002-08-06 Gpi Nil Holdings, Inc. N-oxide of heterocyclic ester, amide, thioester, or ketone hair growth compositions and uses
AU760663B2 (en) * 1998-06-03 2003-05-22 Gpi Nil Holdings, Inc. Small molecule sulfonamide hair growth compositions and uses
US7078424B2 (en) 1998-06-03 2006-07-18 Gpi Nil Holdings, Inc. N-linked sulfonamides of N-heterocyclic carboxylic acids or carboxylic acid isosteres
US7153883B2 (en) 1998-06-03 2006-12-26 Gpi Nil Holdings Inc. Carboxylic acids and carboxylic acid isosteres of N-heterocyclic compounds

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