U.S. patent application number 09/765106 was filed with the patent office on 2001-12-06 for inhibition of hair growth.
Invention is credited to Ahluwalia, Gurpreet S., Shander, Douglas.
Application Number | 20010048932 09/765106 |
Document ID | / |
Family ID | 27371299 |
Filed Date | 2001-12-06 |
United States Patent
Application |
20010048932 |
Kind Code |
A1 |
Ahluwalia, Gurpreet S. ; et
al. |
December 6, 2001 |
Inhibition of hair growth
Abstract
Mammalian hair growth is reduced by applying to the skin a
composition including an inhibitor of an enzyme involved in
arachidonic acid metabolism.
Inventors: |
Ahluwalia, Gurpreet S.;
(Potomac, MD) ; Shander, Douglas; (Acton,
MA) |
Correspondence
Address: |
Fish Richardson P.C.
225 Franklin Street
Boston
MA
02110-2804
US
|
Family ID: |
27371299 |
Appl. No.: |
09/765106 |
Filed: |
January 18, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09765106 |
Jan 18, 2001 |
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09584281 |
May 31, 2000 |
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09584281 |
May 31, 2000 |
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08068257 |
May 28, 1993 |
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6248751 |
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09584281 |
May 31, 2000 |
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08068256 |
May 28, 1993 |
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6239170 |
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Current U.S.
Class: |
424/401 ;
424/73 |
Current CPC
Class: |
A61K 31/54 20130101;
A61K 8/36 20130101; A61K 8/492 20130101; A61K 8/678 20130101; Y10S
514/88 20130101; A61K 8/49 20130101; A61K 8/37 20130101; A61K 31/19
20130101; A61K 8/368 20130101; A61K 31/40 20130101; A61Q 7/02
20130101; A61K 8/445 20130101; A61K 8/35 20130101; A61K 2800/782
20130101; A61K 8/362 20130101; A61K 31/405 20130101; A61K 8/365
20130101; A61K 31/12 20130101 |
Class at
Publication: |
424/401 ;
424/73 |
International
Class: |
A61K 007/15 |
Claims
1. A method of reducing mammalian hair growth, comprising selecting
an area of skin on a mammal from which reduced hair growth is
desired; and applying to the skin a composition including an
inhibitor of an enzyme involved in arachidonic acid metabolism in
an amount effective to reduce hair growth.
2. The method of claim 1, wherein the enzyme is selected from the
group consisting of cyclooxygenase and lipoxygenase.
3. The method of claim 2, wherein the inhibitor is an inhibitor of
cyclooxygenase and lipoxygenase.
4. The method of claim 2, wherein the mammal is a human.
5. The method of claim 3, wherein the mammal is a human.
6. The method of claim 1, wherein said concentration of said
inhibitor in said composition is between 1% and 30%.
7. The method 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.
8. The method of claim 1, wherein the composition is applied to an
area of skin on the face of a human.
9. The method of claim 1, wherein the area of skin is on the arm of
a human.
10. The method of claim 1, wherein the area of skin an on the leg
of a human.
11. The method of claim 1, wherein the composition is applied to an
area of skin on a human with hirsutism.
12. A method of slowing the growth of body hair, comprising
topically applying an effective amount of a compound that inhibits
cyclooxygenase and lipoxygenase in an amount effective to reduce
skin hair growth.
Description
[0001] This application is a continuation-in-part of U.S. Ser. No.
08/068,257, filed May 28, 1993, and a continuation- in-part of U.S.
Ser. No. 08/068,256, filed May 28, 1993.
[0002] The invention relates to the inhibition of hair growth.
[0003] 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.sub.2 and PGH.sub.2. The endoperoxides subsequently are
converted into prostoglandins, which are the primary mediators of
inflammation in the body.
[0004] The enzyme 5-lipoxygenase converts arachidonic acid into
5-hydroperoxyercosa-6,8,11,14-tetraenoic acid, which subsequently
is converted into a family of compounds known as leukotrienes. The
exact biological role of leukotrienes has not yet been
determined.
[0005] 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 an enzyme involved in arachidonic acid
metabolism in an amount effective to reduce hair growth in the
applied area. The inhibitor may, for example, be an inhibitor of
cyclooxygenase or lipoxygenase, or may inhibit both enzymes.
[0006] Some preferred inhibitors are commonly known as non-
steroidal anti-inflammatory drugs (NSAIDs). These drugs include
compounds from a variety of chemical classes.
[0007] One preferred class of NSAIDs are propionic acids, which
include .alpha.-methyl-4-[2-methylpropyl]benzeneacetic acid
(ibuprofen), 6-methoxy-.alpha.-methyl-2-naphthaleneacetic acid
(naproxen), 2-[3-phenoxyphenyl]propionic acid (fenoprofen),
2-[3-benzoylphenyl]propio- nic acid (ketoprofen),
gamma-oxo-[1,1'-biphenyl]-4-butanoic acid (fenoprofen), and
6-chloro-.alpha.-methylcarbazole-2-acetic acid (carprofen).
[0008] 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]-1H-indene-3-acetic acid (sulindac),
1-methyl-5-[p-toluoyl]pyrr- ole-2-acetic acid (tolmetin),
2-[(2,6-dichlorophenyl)amino]-benzeneacetic acid (diclofenac).
[0009] A third preferred class of NSAIDs are salicylates, which
include 2-acetoxybenzoic acid (acetylsalicylic acid) and
5-[2,4-difluorophenyl]sa- licylic acid (diflunisal).
[0010] 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
(mefenamic acid).
[0011] A fifth preferred class of NSAIDs are enolic acids, such as
4-hydroxy-2-methyl-N-2-pyridinyl-2H-thieno
[2,3-e]-1,2-thiazine-3-carboxa- mide-1,1-dioxide (tenoxicam).
[0012] Other NSAIDs like 4-[6-methoxy-2-naphthyl]-2-butanone
(nabumetone) also can be used.
[0013] Examples of other inhibitors that have been found effective
in reducing hair growth include quercetin (3,3',4',5,7-pentahydroxy
flavone), dl-.alpha.-tocopherol, apigenin (4',5,7-trihydroxy
flavone), propyl gallate, NDGA (nondihydroguaianetic acid), and
caffeic acid (3,4-dihydroxycinnamic acid). All of these compounds
are known in the art and are commercially available. Other
inhibitors are known in the art; see, for example, Laughton et al.,
42 Biochemical Pharmacology 1673 (1991).
[0014] 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.
[0015] 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.
[0016] 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
hirsutism. 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.
[0017] 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.
[0018] 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 .mu.l. 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 (mg)
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.
[0019] Some preferred 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.
1TABLE 1 Hair Mass Vehi- Treated Control Percent Compound Dose icle
pH (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 Indo-
20% A 8.0 0.307 .+-. .08 1.844 .+-. .28 83.78 .+-. methacin 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
Salicylates Acetyl- 20% B 5.0 2.126 .+-. .33 3.194 .+-. .21 34.89
.+-. salicylic acid 7.91 Diflunisal 20% D 5.0 0.985 .+-. .10 1.779
.+-. .18 38.32 .+-. 10.73 Anthranilic acids Meclo- 20% A 8.5 0.719
.+-. .14 2.144 .+-. .18 67.77 .+-. fenamic acid 4.79 Mefenamic 10%
A 8.8 0.518 .+-. .13 1.520 .+-. .11 67.18 .+-. acid 6.03 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 Quercetin 5% G 6.0 1.100 .+-. .10 1.543 .+-. .10 27 .+-.
6 10% E 5.5 0.419 .+-. .07 2.679 .+-. .22 83 .+-. 4 Propyl 5% B 7.0
0.870 .+-. .15 2.553 .+-. .16 67 .+-. 5 gallate NDGA 10% B 6.5
0.450 .+-. .11 2.391 .+-. .21 81 .+-. 4 Caffeic acid 5% B 6.0 1.740
.+-. .06 2.424 .+-. .17 26 .+-. 5 15% H 4.0 0.797 .+-. .13 2.148
.+-. .22 62 .+-. 7
[0020]
2TABLE 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% purif:Led 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. Vehicle G: Acetone Vehicle H:
Moisturizing lotion containing common cosmetic ingredients which
include emulsifiers, detergents, and preservatives.
[0021] A preferred inhibitor, indomethacin, was tested for
inhibition of hair growth in various formulations. The results are
presented in Table 3.
3TABLE 3 Hair Growth Inhibition by Indomethacin in Various
Formulations Hair Mass Treated Control Percent Formulation pH (mg)
(mg) Inhibition 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 20% in Vehicle A 8.0 0.307 .+-. .08 1.844 .+-. .28
83.78 .+-. 3.66 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
[0022] 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.
* * * * *