U.S. patent number RE32,112 [Application Number 06/596,290] was granted by the patent office on 1986-04-15 for spironolactone-containing composition and use thereof.
Invention is credited to German Shapiro.
United States Patent |
RE32,112 |
Shapiro |
April 15, 1986 |
Spironolactone-containing composition and use thereof
Abstract
A composition containing spironolactone in an amount effective
to suppress excess androgenic activity. The
spironolactone-containing composition is applied directly to the
skin site afflicted with excess androgens.
Inventors: |
Shapiro; German (Denver,
CO) |
Family
ID: |
26952110 |
Appl.
No.: |
06/596,290 |
Filed: |
April 3, 1984 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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Reissue of: |
266924 |
May 26, 1981 |
04347245 |
Aug 31, 1982 |
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Current U.S.
Class: |
514/172 |
Current CPC
Class: |
A61K
31/585 (20130101) |
Current International
Class: |
A61K
31/585 (20060101); A61K 31/58 (20060101); A61K
031/58 () |
Field of
Search: |
;424/241,238
;514/172 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Shapiro et al., "Journal of Clinical Endocrinology and Metabolism,
51; p. 429 (1980). .
Boisselle et al., "Fertility and Sterility; vol. 32, No. 3, Sep.
1979, pp. 276-279. .
Ober et al., "Annals of Internal Medicine" 89 No. 5 (Part 1) Nov.
1978, pp. 543-544. .
Chem. Abst. 83(21) 172,881t, An Abstract of the Publication in
"Endocrinology", 97(1) pp. 52-58..
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Primary Examiner: Roberts; Elbert L.
Attorney, Agent or Firm: Wegner & Bretschneider
Claims
I claim:
1. A composition for effectively suppressing excess androgenic
activity which occurs at a skin site so as to effectively treat
.[.hirsuitisum.]. .Iadd.hirsutism, .Iaddend.said composition being
.[.directly applied.]. .Iadd.in a form suitable for direct
application .Iaddend.to said skin site .[., the composition.].
.Iadd.and .Iaddend.consisting essentially of .[.: a liquid carrier
selected from the group consisting of alcohol, urea, mineral oil
and white petrolatum; and .]. spironolactone in an amount of from
about 0.25 wt. % to about 5.0 wt. %.Iadd., .Iaddend.which
effectively suppresses excess androgenic activity at said skin
site.Iadd., in a suitable carrier therefor; said composition having
characteristics ranging from those of a cream to those of an
ointment. .Iaddend.
2. The composition of claim 1 wherein .[.said liquid.]. .Iadd.the
.Iaddend.carrier is white petrolatum.
3. The composition of claim 1 further consisting essentially
of:
a solubilizer selected from the group consisting of stearyl
alcohol, cetyl alcohol or mixtures thereof, said solubilizer being
present in an amount of from about 1.5 wt. % to about 3.0 wt. % so
as to aid incorporation of said spironolactone into said
carrier.
4. The composition of claim 3 further consisting essentially of a
viscosifier in an amount sufficient to aid in emulsification of
said solubilizer in said carrier.
5. The composition of claim 1 further consisting essentially
of:
a preservative selected from the group consisting of
methylhydroxybenzoate, propylhyroxybenzoate, or mixtures thereof,
said preservative being employed in an amount sufficient to extend
the useful like of said composition.
6. In a process for treating at least one skin site characterized
by excess androgenic activity so as to effectively suppress said
excess androgenic activity, the improvement comprising: directly
applying a spironolactone-containing composition to said at least
one skin site, said composition consisting essentially of .[.a
liquid carrier selected from the group consisting of alcohol, urea,
mineral oil and white petroleum and.]. spironolactone in an amount
of from about 0.25 wt. % to about 5.0 wt. % .Iadd.in a suitable
carrier therefor, .Iaddend.which effectively suppresses androgenic
activity at said skin site.
7. The process of claim 6 wherein said .[.liquid.]. carier is white
petrolatum.
8. The process of claim 6 wherein said composition further consists
essentially of a solubilizer selected from the group consisting of
stearyl alcohol, cetyl alcohol or mixtures thereof, said
solubilizer being present in an amount of from about 1.5 wt. % to
about 3.0 wt. % so as to aid incorporation of said spironolactone
into said carrier.
9. The process of claim 8 wherein said composition further consists
essentially of a viscosifier in an amount sufficient to aid in
emulsification of said solubilizer in said carrier.
10. The process of claim 6 wherein said composition further
consists essentially of a preservative selected from the group
consisting of methylhydroxybenzoate, propylhydroxybenzoate, or
mixtures thereof, said preservative being employed in an amount
sufficient to extend the useful life of said composition. .Iadd.11.
The process according to claim 6 for the treatment of hirsutism
caused by excess androgenic activity. .Iaddend. .Iadd.12. The
process according to claim 6 for the treatment of acne caused by
excess androgenic activity. .Iaddend.
Description
BACKGROUND OF THE INVENTION
I. Technical Field
The present invention relates to a composition containing
spironolactone, and more particularly, to such a composition
containing spironolactone for application directly to human skin
for effectively suppressing excess androgenic activity at the skin
site.
II. Background Art
In most physically normal women, androgens or male sex homones are
effectively synthesized by both ovaries and adrenals. However, in
certain females afflicted with polycystic ovarian disease or
ovarian hyperthecosis, the ovaries appear to be the major source of
enhanced androgen secretion, especially testosterone. Such excess
androgen secretion in women has been linked to increased masculine
characteristics, in particular, hirsuitism.
A number of prior art compounds possessing antiandrogenic activity
have been utilized in treatment of hirsuitism, as detailed in: A
Novel Use of Spironolactone; Treatment of Hirsuitism, "Journal of
Clinical Endocrinology and Metabolism" Shapiro, et al., Vol. 51,
No. 3, pp. 429-432, Jan. 4, 1980; Spironolactone Therapy for
Hirsuitism in a Hyper androgenic Woman, "Annals of Internal
Medicine", Ober, et al., Vol. 89, No. 5 (Part 1), pp. 643, 644,
November, 1978; and New Therapeutic Approach to the Hirsute
Patient, "Fertility and Sterility", Boiselle, et al., Vol. 32, No.
3, pp. 276-279, September, 1979. Cyproterone acetate has been
orally administered to treat hirsuitism and has proved effective
therein. However, severe side effects, such as, adrenal
insufficiency and loss of libido have rendered its use undesirable.
Oral contraceptives and corticosteroids have also been utilized for
treatment with androgenic access, although numerous side effects
have minimized the use thereof. Spironolactone has also been orally
administered for treatment of excess androgens in women. However,
when spironolactone is administered orally, the concentration of
spironolactone must be increased to a level at which equal
concentrations are provided to all tissue even though specific skin
tissue at which excess androgenic activity occurs may be the only
desired area to be treated. If spironolactone is administered
orally on a daily basis, side effects, such as, metrorrhagia (i.e.,
disruption of the menstrual cycle during which non-menstrual
bleeding from the uterus occurs) and electrolytic disturbance
involving potassium accumulation in the blood, may occur. Thus,
oral ingestion of spironolactone must be constantly monitored by a
licensed physician which is both costly and time consuming. In
addition, as spironolactone should only be orally administered to
women between the fifth and twenty second day of their menstrual
cycle to aovid metrorrahgia, a woman must constantly be appraised
of and cognizant of this fact. Finally, even when spironolatone is
properly administered orally, large amounts of tissue which are not
afflicted with an excess of androgenic activity are unnecessarily
intoxicated with spironolactone.
Thus, it can be appreciated that a need exists for a composition
possessing antiandrogenic activity which can be applied directly to
human skin for effectively suppressing the excess androgenic
activity thereof.
BRIEF SUMMARY OF THE INVENTION
The present invention relates to a spironolactone containing
composition for effectively suppressing excess androgenic activity
which occurs at a skin site to effectively treat, inter alia,
hirsuitism. The composition consists essentially of an effective
amount of spironolactone incorporated into a carrier. A
solubilizer, a viscosifier and a preservative may also be
selectively incorporated into the composition of the present
invention as desired.
DETAILED DESCRIPTION
The present invention relates to a spironolactone-containing
composition for application to an area of human skin afflicted with
hirsuitism for effective treatment thereof. Applicant has
discovered that by direct application of spironolactone to an
afflicted area of human skin via a suitable carrier, hirsuitism in
the afflicted area is effectively controlled and reduced while
substantially eliminating any side effects attendant with use of
spironolactone. It is believed that spironolactone suppresses
androgenic activity in the skin which is a major site of androgene
metabolism.
The composition of the present invention comprises an effective
amount of spironolactone and a suitable .[.liquid.]. carrier. As
utilized throughout the description, the term "spironolactone"
refers to aldactone
[3-(3-oxo-7-acethylthio-17-hydroxy-antrost-4-en-17-4yl) propionic
acid lactone]. The .[.liquid.]. carrier can be any .[.liquid.].
carrier which can function to transport an active ingredient to the
area of human skin to be treated and preferably which is capable of
being rubbed into the skin so as to be transparent in appearance.
Exemplary .[.liquid.]. carriers are alcohol, urea, mineral oil and
white petrolatum. Depending upon the exact .[.liquid.]. carrier
employed and the addition of any viscosifiers, the composition of
the present invention can have characteristics ranging from those
of a cream to an ointment.
In accordance with the preferred embodiment, spironolactone is
incorporated into the composition of the present invention in the
amount of from about 0.25 wt. % to about 2.0 wt. %, and most
preferably about 1.0 wt. %. Spironolactone can be incorporated into
a suitable carrier in a preselected amount as dictated by the
concentration ranges just described.
A solubilizer, such as, stearyl alcohol, or cetyl alcohol, can be
utilized in the composition of the present invention to solubilize
spironolactone therein so as to aid incorporation of spironolactone
into the carrier. The solubilizer can be incorporated into the
composition of the present invention in an amount of from about 1.5
wt. % to about 3.0 wt. %. A viscosifier, such as, cottonseed oil,
can also be incorporated into the composition of the present
invention where a lower viscosity is desirable and/or to aid in
emulsification of the solubilizer within the carrier. The
viscosifier can be incorporated into the composition of the present
invention in an amount of from about 3 wt. % to about 6 wt. %. A
preservative, such as, methylhydroxybenzoate,
propylhydroxybenzoate, or mixtures thereof, can also be
incorporated into the composition of the present invention in an
amount from about 0.25 wt. % to about 0.50 wt. %.
The preferred composition of the present invention is about 1.0 wt.
% spironolactone, about 1.5 wt. % stearyl alcohol, about 3.0 wt. %
cottonseed oil, about 0.25 wt. % methylhydroxybenzoate, and about
94.25 wt. % white petrolatum.
The composition of the present invention may be manually applied to
the afflicted area of skin and rubbed until absorbed fully into the
area. Concomitant with a reduction of hirsuitism in the area
treated, is an improvement of acne which is also a disorder known
to be androgen dependent. Thus, it can be appreciated that in
utilizing the spironolactone-containing composition of the present
invention, the entire physical system of an individual treated is
not intoxicated with spironolactone but only that surface skin area
to be treated, thus minimizing side effects attendant with
application of spironolactone and constant physician monitoring
which is attendent with oral ingestion of spironolactone. And
although the composition of the present invention has been
described as effective in treating hirsuitism in women, the
composition is also effective in retarding baldness in men since
such baldness is characterized by excess andgrogenic activity.
While various embodiments and modifications of the invention have
been described in the foregoing description, further modifications
will be apparent to those skilled in the art. Such modifications
are included within the scope of this invention as defined by the
following claims.
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