WO1994027586A1 - Inhibition of hair growth - Google Patents

Inhibition of hair growth Download PDF

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Publication number
WO1994027586A1
WO1994027586A1 PCT/US1994/005360 US9405360W WO9427586A1 WO 1994027586 A1 WO1994027586 A1 WO 1994027586A1 US 9405360 W US9405360 W US 9405360W WO 9427586 A1 WO9427586 A1 WO 9427586A1
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WO
WIPO (PCT)
Prior art keywords
acid
inhibitor
hair growth
composition
skin
Prior art date
Application number
PCT/US1994/005360
Other languages
French (fr)
Inventor
Gurpreet S. Ahluwalia
Douglas Shander
Original Assignee
Handelman, Joseph, H.
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Filing date
Publication date
Application filed by Handelman, Joseph, H. filed Critical Handelman, Joseph, H.
Priority to JP50071395A priority Critical patent/JP3727338B2/en
Priority to DE69427756T priority patent/DE69427756T2/en
Priority to EP94919136A priority patent/EP0700288B1/en
Priority to CA002163535A priority patent/CA2163535C/en
Priority to AU70181/94A priority patent/AU677346B2/en
Publication of WO1994027586A1 publication Critical patent/WO1994027586A1/en

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    • 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
    • A61Q7/02—Preparations for inhibiting or slowing hair growth
    • 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
    • A61K31/12—Ketones
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • 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
    • 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
    • A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35—Ketones, e.g. benzophenone
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • 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
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A61K8/445—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof aromatic, i.e. the carboxylic acid directly linked to the aromatic ring
    • 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
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Definitions

  • the invention relates to the inhibition of hair growth.
  • Arachidonic acid is released from membrane lipids in response to injury or other irritation.
  • the enzyme cyclooxygenase converts arachidonic acid into cyclic endoperoxides commonly known as PGG 2 and GH 2 .
  • the endoperoxides subsequently are converted into prostoglandins, which are the primary mediators of inflammation in the body.
  • mammalian (including human) hair growth can be inhibited by applying to the skin a composition including an inhibitor of cyclooxygenase in an amount effective to reduce hair growth in the applied area.
  • NSAIDs non-steroidal anti-inflammatory drugs
  • NSAIDs are propionic acids, which include ⁇ -methyl-4- [2- methylpropyllbenzeneacetic acid (ibuprofen) , 6- methoxy- ⁇ -methyl-2-naphthaleneacetic acid
  • naproxen 2- [3-phenoxyphenyl]propionic acid (fenoprofen), 2- [3-benzoylphenyl]propionic acid (ketoprofen) , ga ⁇ na-oxo- [1,1' -biphenyl] -4- butanoic acid (fenoprofen) , and 6-chloro- ⁇ - methylcarbazole-2-acetic acid (carprofen) .
  • NSAIDs are indoleacetic acids, which include 1- [p- chlorobenzoyl] -5-methoxy-2-methylindole-3-acetic acid (indomethacin) , 5-fluoro-2-methyl-1- [ (4- (methylsulfinyl)phenyl) methylene) -lH-indene-3- acetic acid (sulindac) , l-methyl-5- [p- toluoyl]pyrrole-2-acetic acid (tolmetin) , 2- [ (2,6-dichlorophenyl)amino]benzeneacetic acid (diclofenac) .
  • indoleacetic acids include 1- [p- chlorobenzoyl] -5-methoxy-2-methylindole-3-acetic acid (indomethacin) , 5-fluoro-2-methyl-1- [ (4- (methylsulfinyl)phenyl) methylene) -lH-
  • a third preferred class of NSAIDs are salicylates, which include 2-acetoxybenzoic acid (acetylsalicylic acid) and 5- [2,4- difluorophenyl] salicylic acid (diflunisal) .
  • a fourth preferred class of NSAIDs are anthranilic acids, which include 2- [(2,6- dichloro-3-methylphenyl)amino]benzoic acid (meclofenamic acid) and 2- [ (2,3-dimethylphenyl) amino]benzoic acid ( efenamic acid) .
  • a fifth preferred class of NSAIDs are enolic acids, such as 4-hydroxy-'2-methyl-N-2- pyridinyl-2H-thieno[2,3-e]-l,2-thiazine-3- carboxamide-1,1-dioxide (tenoxicam) .
  • NSAIDs like 4- [6-methoxy-2- naphthyl] -2-butanone (nabumetone) also can be used.
  • the composition preferably includes a non-toxic dermatologically acceptable vehicle or carrier which is adapted to be spread on the skin.
  • suitable vehicles are acetone, alcohols, or a cream, lotion, or gel which can effectively deliver the active compound.
  • a penetration enhancer may be added to the vehicle to further enhance the effectiveness of the formulation.
  • concentration of the inhibitor in the composition may be varied over a wide range up to a saturated solution, preferably from 1 to 30% by weight or even more; the reduction of hair growth increases as the amount of inhibitor applied increases per unit area of skin.
  • the maximum amount effectively applied is limited only by the rate at which the inhibitor penetrates the skin. Generally, the effective amounts range from 100 to 3000 micrograms or more per square centimeter of skin.
  • the composition should be applied to the area of the body where it is desired to inhibit hair growth.
  • the composition can be applied to the face, particularly to the beard area of the face, i.e., the cheek, neck, upper lip, and chin.
  • the composition can also be applied to the legs, arms, torso or armpit.
  • the composition is particularly suitable for the treatment of hirsatism.
  • the composition should be applied once or twice a day, or even more frequently, for at least three months to achieve a perceived reduction in hair growth.
  • flank organs of each of a group of hamsters are depilated by applying a thioglycolate based chemical depilatory (Surgex) .
  • a thioglycolate based chemical depilatory Surgex
  • Percent-reduction of hair growth is calculated by subtracting the hair mass ( g) value of the test compound treated side from the hair mass value of the vehicle treated side; the delta value obtained is then divided by the hair mass value of the vehicle treated side, and the resultant number is multiplied by 100.
  • Vehicle A 68% Purified water, 16% ethanol (200 proof) , 5% propylene glycol, 5% dipropylene glycol, 4% benzyl alcohol, 2% propylene carbonate.
  • Vehicle B 80% Ethanol (190 proof), 17.5% purified water, 2% propylene glycol dipelargonate, 0.5% propylene glycol.
  • Vehicle C 30% Dipropylene glycol, 25% acetone, 15% ethanol (200 proof) , 10% benzyl alcohol, 10% dimethyl sulfoxide (DMSO) , 10% propylene glycol.
  • DMSO dimethyl sulfoxide
  • Vehicle D 35% Dipropylene glycol, 30% ethanol (200 proof) , 20% acetone, 10% propylene glycol, 5% benzyl alcohol.
  • Vehicle E 35% Dipropylene glycol, 30% ethanol (200 proof) , 25% acetone, 10% benzyl alcohol.
  • Vehicle F 35% Dipropylene glycol, 35% ethanol (200 proof) , 15% acetone, 10% DMSO, 5% benzyl alcohol.

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  • Health & Medical Sciences (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)
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Abstract

Mammalian hair growth is reduced by applying to the skin a composition including an inhibitor of cyclooxygenase.

Description

INHIBITION OF HAIR GROWTH The invention relates to the inhibition of hair growth.
Arachidonic acid is released from membrane lipids in response to injury or other irritation. The enzyme cyclooxygenase converts arachidonic acid into cyclic endoperoxides commonly known as PGG2 and GH2. The endoperoxides subsequently are converted into prostoglandins, which are the primary mediators of inflammation in the body.
It has now been found that mammalian (including human) hair growth can be inhibited by applying to the skin a composition including an inhibitor of cyclooxygenase in an amount effective to reduce hair growth in the applied area.
The preferred inhibitors are commonly known as non-steroidal anti-inflammatory drugs (NSAIDs) . These drugs include compounds from a variety of chemical classes.
One preferred class of NSAIDs are propionic acids, which include α-methyl-4- [2- methylpropyllbenzeneacetic acid (ibuprofen) , 6- methoxy-α-methyl-2-naphthaleneacetic acid
(naproxen) , 2- [3-phenoxyphenyl]propionic acid (fenoprofen), 2- [3-benzoylphenyl]propionic acid (ketoprofen) , gaππna-oxo- [1,1' -biphenyl] -4- butanoic acid (fenoprofen) , and 6-chloro-α- methylcarbazole-2-acetic acid (carprofen) .
Another preferred class of NSAIDs are indoleacetic acids, which include 1- [p- chlorobenzoyl] -5-methoxy-2-methylindole-3-acetic acid (indomethacin) , 5-fluoro-2-methyl-1- [ (4- (methylsulfinyl)phenyl) methylene) -lH-indene-3- acetic acid (sulindac) , l-methyl-5- [p- toluoyl]pyrrole-2-acetic acid (tolmetin) , 2- [ (2,6-dichlorophenyl)amino]benzeneacetic acid (diclofenac) .
A third preferred class of NSAIDs are salicylates, which include 2-acetoxybenzoic acid (acetylsalicylic acid) and 5- [2,4- difluorophenyl] salicylic acid (diflunisal) .
A fourth preferred class of NSAIDs are anthranilic acids, which include 2- [(2,6- dichloro-3-methylphenyl)amino]benzoic acid (meclofenamic acid) and 2- [ (2,3-dimethylphenyl) amino]benzoic acid ( efenamic acid) .
A fifth preferred class of NSAIDs are enolic acids, such as 4-hydroxy-'2-methyl-N-2- pyridinyl-2H-thieno[2,3-e]-l,2-thiazine-3- carboxamide-1,1-dioxide (tenoxicam) .
Other NSAIDs like 4- [6-methoxy-2- naphthyl] -2-butanone (nabumetone) also can be used.
The composition preferably includes a non-toxic dermatologically acceptable vehicle or carrier which is adapted to be spread on the skin. Examples of suitable vehicles are acetone, alcohols, or a cream, lotion, or gel which can effectively deliver the active compound. In addition, a penetration enhancer may be added to the vehicle to further enhance the effectiveness of the formulation. The concentration of the inhibitor in the composition may be varied over a wide range up to a saturated solution, preferably from 1 to 30% by weight or even more; the reduction of hair growth increases as the amount of inhibitor applied increases per unit area of skin.
The maximum amount effectively applied is limited only by the rate at which the inhibitor penetrates the skin. Generally, the effective amounts range from 100 to 3000 micrograms or more per square centimeter of skin.
The composition should be applied to the area of the body where it is desired to inhibit hair growth. Typically, the composition can be applied to the face, particularly to the beard area of the face, i.e., the cheek, neck, upper lip, and chin. The composition can also be applied to the legs, arms, torso or armpit. The composition is particularly suitable for the treatment of hirsatism. In humans, the composition should be applied once or twice a day, or even more frequently, for at least three months to achieve a perceived reduction in hair growth.
Reduction of hair growth is demonstrated when the frequency of hair removal is reduced, or the subject perceives less hair on the treated site, or quantitatively, when the weight of hair removed by shaving (i.e., hair mass) is reduced. Male intact Golden Syrian hamsters are considered acceptable models for human beard hair growth in that they display oval shaped flank organs, one on each side, each about 8 mm. in major diameter, which grow thick black and coarse hair similar to human beard hair. These organs produce hair in response to androgens in the hamster.
To evaluate the effectiveness of a particular inhibitor in reducing hair growth, the flank organs of each of a group of hamsters are depilated by applying a thioglycolate based chemical depilatory (Surgex) . To one organ of each animal 10 μl. of vehicle alone once a day is applied, while to the other organ of each animal an equal amount of vehicle containing the inhibitor is applied. After thirteen applications (one application per day for five days a week) , the flank organs are shaved and the amount of recovered hair (hair mass) from each is weighed. Percent-reduction of hair growth is calculated by subtracting the hair mass ( g) value of the test compound treated side from the hair mass value of the vehicle treated side; the delta value obtained is then divided by the hair mass value of the vehicle treated side, and the resultant number is multiplied by 100.
The preferred cyclooxygenase inhibitors were tested according to the above procedure. The results are presented in Table 1; the vehicles used to deliver the inhibitors are reported in Table 2.
Figure imgf000007_0001
TABLE 1 Hair Mass
Compound Dose Vehicle pH Treated Control Percent (mg) (mg) Inhibition
Propionic acids
Ibuprofen 20% B 5.0 1.160 ± .16 1.704 ± .15 30.33 ± 7.74
Naproxen 20% A 8.5 0.771 ± .11 2.108 ± .15 62.52 ± 5.40
Fenoprofen 20% D 6.0 0.373 ± .10 1.276 ± .11 70.58 ± 7.04
Ketoprofen 20% B 4.5 0.895 ± .20 1.293 ± .26 29.70 ± 5.10
Carprofen 20% C 6.0 0.776 ± .11 1.274 ± .19 29.69 ±11.06
Indoleacetic acids
Indomethacin 20% A 8.0 0.307 ± .08 1.844 ± .28 83.78 ± 3.66
Sulindac 20% A 9.0 0.517 ± .09 2.539 ± .27 79.90 ± 3.27
Tolmetin 20% A 8.5 1.459 ± .16 2.344 ± .24 37.85 ± 3.35
Diclofenac 20% B 8.0 0.648 ± .10 1.769 ± .19 63.40 ± 5.21
TABLE 1 (Continued) Hair Mass
Compound Dose Vehicle pH Treated Control Percent ( g) (mg) Inhibition
Salicvlates
Acetyl- 20% B 5.0 2.126 ± .33 3.194 ± .21 34.89 ± 7.91 salicylic acid
Diflunisal 20% D 5.0 0.985 ± .10 1.779 ± .18 38.32 ±10.73
Anthranilic acids I
Meclofenamic 20% A 8.5 0.719 ± .14 2.144 ± .18 67.77 ± 4.79 ι acid
Mefenamic 10% A 8.8 0.518 ± .13 1.520 ± .11 67.18 ± 6.03 acid
Enolic acids
Tenoxican 15% B 8.0 0.326 ± .08 2.116 ±0.24 85.38 ± 2.91
Other
Nabumetone 15% E 6.0 1.267 ± .23 1.684 ± .21 23.23 ±10.41
TABLE 2 Vehicles Used in Hair Mass Assays
Vehicle A: 68% Purified water, 16% ethanol (200 proof) , 5% propylene glycol, 5% dipropylene glycol, 4% benzyl alcohol, 2% propylene carbonate.
Vehicle B: 80% Ethanol (190 proof), 17.5% purified water, 2% propylene glycol dipelargonate, 0.5% propylene glycol.
Vehicle C: 30% Dipropylene glycol, 25% acetone, 15% ethanol (200 proof) , 10% benzyl alcohol, 10% dimethyl sulfoxide (DMSO) , 10% propylene glycol.
Vehicle D: 35% Dipropylene glycol, 30% ethanol (200 proof) , 20% acetone, 10% propylene glycol, 5% benzyl alcohol.
Vehicle E: 35% Dipropylene glycol, 30% ethanol (200 proof) , 25% acetone, 10% benzyl alcohol.
Vehicle F: 35% Dipropylene glycol, 35% ethanol (200 proof) , 15% acetone, 10% DMSO, 5% benzyl alcohol.
A preferred inhibitor, indomethacin, was tested for inhibition of hair growth in various formulations. The results are presented in Table 3.
TABLE 3
Hair Growth Inhibition by Indomethacin in Various Formulations
Formulation EH Hair Mass Percent Inhibition
Treated Control (mg) (mg)
5% in Vehicle A 7.5 1.248 ± .20 2.173 ± .14 43.41 ± 7.75
10% in Vehicle A 7.5 1.084 ± .11 2.364 ± .22 53.32 ± 4.17
15% in Vehicle A 7.5 0.768 ± .10 2.443 ± .15 68.77 ± 3.02 I
0
20% in Vehicle A 8.0 0.307 ± .08 1.844 ± .28 83.78 ± 3.66 I
20% in Vehicle B 7.0 0.261 ± .01 1.653 ± .15 83.37 ± 1.46
10% in Vehicle F 5.5 0.679 ± .08 1.436 ± .20 49.89 ± 5.54
20% in Vehicle F 5.5 0.324 ± .08 1.491 ± .14 78.43 ± 4.39
Figure imgf000010_0001
It will be appreciated by those skilled in the art that the invention can be performed within a wide range of equivalent parameters of composition and conditions without departing from the spirit or scope of the invention or of any embodiment thereof.

Claims

C L A I M S
1. A process of inhibiting mammalian hair growth, comprising applying to the skin a composition including an inhibitor of cyclooxygenase in an amount effective to reduce hair growth.
2. The process of claim 1, wherein said inhibitor is one or more of o-methyl-4- [2- methylpropyl]benzeneacetic acid, 6-methoxy-α- methyl-2-naphthaleneacetic acid, 2- [3- phenoxyphenyl]propionic acid, 2- [3- benzoylphenyl]propionic acid, gamma-oxo- [1,1' - biphenyl] -4-butanoic acid, 6-chloro-cκ- methylcarbazole-2-acetic acid, 1- [p- chlorobenzoyl] -5-methoxy-2-methylindole-3-acetic acid, 5-fluoro-2-methyl-l- [(4- (methylsulfinyl)phenyl) ethylene] -1H-indene-3- acetic acid, l-methyl-5- [p-toluoyl]pyrrole-2- acetic acid, 2- [ (2,6-dichlorophenyl)amino] - benzeneacetic acid, 2-acetoxybenzoic acid, 5- [2,4-difluorophenyl] salicylic acid, 2- [(2,6- dichloro-3-methylphenyl)amino]benzoic acid, 2- [ (2,3-dimethylphenyl)amino]benzoic acid, 4- hydroxy-2-methyl-N-2-pyridinyl-2H-thieno[2,3-e] - l,2-thiazine-3-carboxamide 1,1-dioxide, or 4- [6- methoxy-2-naphthyl] -2-butanone.
3. The process of claim 1, wherein said inhibitor is a nonsteroidal anti-inflammatory drug.
4. The process of claim 3, wherein said nonsteroidal anti-inflammatory drug is one or more of a propionic acid, an indolacetic acid, a salicylate, an anthranilic acid, or an enolic acid.
5. The process of claim 1, wherein the concentration of said inhibitor in said composition is between 1% and 30%.
6. The process of claim 1, wherein the composition is applied to the skin in an amount of from 100 to 3000 micrograms of said inhibitor per square centimeter of skin.
7. The process of claim 1, wherein the composition is applied to the skin on the face of said mammal.
8. A method of producing a composition for inhibiting mammalian hair growth, which comprises selecting an inhibitor of cyclooxygenase, and combining said inhibitor, in an amount effective to reduce hair growth, with a non-toxic, dermatologically acceptable vehicle or carrier.
9. A method according to claim 8, wherein said vehicle or carrier is adapted to be spread upon the skin of a mammal.
10. A method according to claim 8, wherein said inhibitor is as defined in any one of claims 2 to 5.
11. The new use of an inhibitor of cyclooxygenase for reducing hair growth.
12. A composition when used for inhibiting hair growth, which includes an inhibitor of cyclooxygenase in an amount effective to reduce hair growth and a non-toxic, dermatologically acceptable vehicle or carrier.
13. A composition according to claim 12, wherein said inhibitor is as defined in any one of claims 2 to 5.
PCT/US1994/005360 1993-05-28 1994-05-16 Inhibition of hair growth WO1994027586A1 (en)

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EP94919136A EP0700288B1 (en) 1993-05-28 1994-05-16 Inhibition of hair growth
CA002163535A CA2163535C (en) 1993-05-28 1994-05-16 Inhibition of hair growth
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DE69427756D1 (en) 2001-08-23
JP3727338B2 (en) 2005-12-14
CA2163535A1 (en) 1994-12-08
ZA943611B (en) 1995-01-25
EP0700288A1 (en) 1996-03-13
DE69427756T2 (en) 2002-05-23
US6248751B1 (en) 2001-06-19
ES2159560T3 (en) 2001-10-16
AU677346B2 (en) 1997-04-17
JPH08510734A (en) 1996-11-12
EP0700288B1 (en) 2001-07-18
AU7018194A (en) 1994-12-20
CA2163535C (en) 2002-02-26

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