U.S. patent application number 10/097001 was filed with the patent office on 2002-10-24 for topical preparation for treating acne and hirsutism.
Invention is credited to Goodman, David S..
Application Number | 20020155180 10/097001 |
Document ID | / |
Family ID | 24250970 |
Filed Date | 2002-10-24 |
United States Patent
Application |
20020155180 |
Kind Code |
A1 |
Goodman, David S. |
October 24, 2002 |
Topical preparation for treating acne and hirsutism
Abstract
An improved method and preparation for the treatment of acne and
hirsutism comprises topically applying an effective amount of a saw
palmetto berry extract, and preferably one or more low irritability
constituents that enhance penetration of the extract into hair
follicle sebaceous glands. The low irritability penetration aid may
be selected from the group consisting of adapalene, tretinoin,
tretinoin gel microsponges, retinaldehyde, retinol, tazarotene,
beta hydroxy acids (salicylic acid), azelaic acid, and alpha
hydroxy acids (glycolic acid) as well as polyolprepolymer-2.
Inventors: |
Goodman, David S.; (Naples,
FL) |
Correspondence
Address: |
Robert I. Pearlman, Esq.
Riker, Danzig, Scherer, Hyland & Perretti LLP
Headquarters Plaza
One Speedwell Avenue
Morristown
NJ
07962
US
|
Family ID: |
24250970 |
Appl. No.: |
10/097001 |
Filed: |
March 13, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10097001 |
Mar 13, 2002 |
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09563555 |
May 3, 2000 |
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6358541 |
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Current U.S.
Class: |
424/727 ;
514/859 |
Current CPC
Class: |
A61K 8/37 20130101; A61K
8/92 20130101; A61K 8/63 20130101; A61Q 5/00 20130101; A61K 8/046
20130101; A61Q 5/06 20130101; A61K 8/9789 20170801; A61Q 7/00
20130101; A61K 8/368 20130101; A61K 8/362 20130101; A61K 8/671
20130101; A61K 8/365 20130101 |
Class at
Publication: |
424/727 ;
514/859 |
International
Class: |
A61K 035/78; A01N
025/00 |
Claims
1. A method for the treatment of acne or hirsutism comprising
topically applying to the affected area an effective amount of saw
palmetto berry extract.
2. The method of claim 1, wherein said saw palmetto berry extract
is applied as a composition containing one or more penetrating
enhancing agents.
3. The method of claim 1, wherein said penetrating enhancing
constituents are selected from the group consisting of adalpalene,
tretinoin, tretinoin gel microsponges, retinaldehyde, retinol,
tazarotene, beta hydroxy acids, azelaic acid, and alpha hydroxy
acids.
4. The method of claim 1, wherein said saw palmetto berry extract
comprises at least 0.5 wt. % of the topically applied
composition.
5. A method for the treatment of acne or hirsutism comprising: (a)
washing the affected area with a mild soap, (b) applying to the
affected area a topical preparation comprising an effective amount
of saw palmetto berry extract containing one or more penetrating
enhancing constituents; (c) and increasing the frequency of said
application if no allergy irritation occurs.
6. The method of claim 5, wherein said topical preparation is
applied once daily and thereafter increased to twice daily if no
allergy or irritation occurs.
7. The method of claim 6, wherein once a steady state condition has
been reached, the frequency of topical application of said
composition is reduced to once daily.
8. The method of claim 1, which is employed for the treatment of
acne wherein improvement is noted within approximately one month of
treatment.
9. The method of claim 5, wherein the present topical preparation
is applied after mild soap, but before application of moisturizer,
sunscreen or makeup.
10. A low irritability topical preparation for the treatment of
acne and/or hirsutism comprising an effective amount of saw
palmetto berry extract containing phytosterols and one or more
penetration enhancing constituents selected from the group
consisting of adapalene, tretinoin, tretinoin gel microsponges,
retinaldehyde, retinol, tazarotene, beta hydroxy acids, azelaic
acid, and alpha hydroxy acids.
11. The topical preparation of claim, 10, wherein the penetration
enhancing constituents of a first member selected from the group
consisting of adapalene, tretinoin, tretinoin gel microsponges, and
a second member selected from the group consisting of beta hydroxy
acid and alpha hydroxy acids.
12. The topical preparation of claim 10, wherein the alpha hydroxy
acid is glycolic acid.
13. The topical preparation of claim 10, wherein the beta hydroxy
acid is salicylic acid.
14. The topical preparation of claim 10, wherein the concentration
of saw palmetto berry extract is at least 0.5 wt. %.
15. A topical preparation of claim 10, wherein the preparation is
in a topical vehicle selected from the group consisting of a
liquid, a dampened pad, a lotion or cream.
Description
RELATED APPLICATIONS
[0001] This application is a Continuation-in-Part of U.S. Ser. No.
09/563,555 filed May 3, 2000 for the instant inventor.
BACKGROUND OF THE INVENTION
[0002] This invention relates to an improved preparation and method
for treating both acne and hirsutism, or unwanted facial and body
hair in women; and more particularly to a preparation comprising a
topically active extract of saw palmetto berries, with one or more
compounds which exhibit low irritability and enhance penetration of
the extract into hair follicles and sebaceous glands.
Pathogenens of Acne
[0003] Acne is caused by a complex interaction of excessive sebum
production colonization of hair follicles by Proprionibasterium
acnes, and follicular plugging or comedone formation.
[0004] Sebum is the oily secretion of sebaceous glands. These
glands drain directly into hair follicles and are present mainly on
the face, chest and back. Sebum production is predominantly
controlled by androgens manufactured in the testes, adrenal glands,
and ovaries. High levels of androgens are associated with increased
sebum production.
[0005] Dihydrotestosterone (hereinafter referenced to as DHT), is
the prime androgen responsible for excessive sebum production. Skin
affected by acne contains two to thirty times more DHT than normal
skin. Much of this excess of DHT is due to conversion of
testosterone into DHT directly in acne prone skin. This conversion
is mediated by the enzyme 5-alpha reductase.
[0006] Follicular plugs consist of collections of sebum,
keratinocytes, and keratin. They occlude the follicular orifice and
prevent the further drainage of the contents of the follicle. The
greater the quantity of sebum, the more likely that a follicular
plug will form. The clogged follicle is known as a comedone. Sebum
production into a comedone or clogged follicle, as well as the
proliferation of Proprionibacterium acne, a bacteria which commonly
colonizes hair follicles ultimately leads to the rupture of the
wall of the comedone and allows the spilling of sebum and bacteria
into the surrounding skin. Thus leads to the formation of
inflammatory acne lesions.
[0007] Saw palmetto, (serenoa repens), is a small berry-bearing
palm native to the southeast United States. Saw palmetto berry
extract, (hereinafter referred to as SPBE) has been shown to block
5-alpha reductase, the enzyme that converts the hormone
testosterone into dihydrotestosterone. Once again, this is the
major androgen implicated in stimulating sebum production. SPBE
also blocks the binding of DHT to androgen receptors. Thus, in
treating acne SPBE may act either by blocking the formation of DHT,
by inhibiting binding of DHT to the androgen receptors, or
both.
[0008] A need exists for a SPBE formulation and method for
effectively treating acne. Especially needed is a SPBE topical
formulation that offers efficacy and high penetration into hair
follicles and sebaceous glands, while causing minimal
irritation.
Acne Treatments
[0009] Current accepted acne therapies include both topical and
systemic products. Topical products include:
[0010] (a) antibiotics such as erythromycin, clindamycin and benzyl
peroxide which disease the number of Proprionibasterium acnes in
follicles,
[0011] (b) Keratinolytics such as salicylic acid and glycolic acid
which help remove keratin from the surface of the skin and thereby
prevent comedone formation, and
[0012] (c) comedolytics such tretinoin, adapalene and tazarotene
which decrease keratinocyte proliferation at follicular openings
and thereby also help prevent comedone formation.
Hirsutism
[0013] Hirsutism is the abnormal growth of large terminal hairs in
women in androgen sensitive areas. Most often these areas include
the mustache, beard and chin areas, as well as the pubic escutcheon
and lower abdomen. Unwanted hair may also be present on the thighs
and trunk as well. Terminal hair growth in these areas is usually
due to excess androgenic stimulation of the hair follicles.
[0014] Idiopathic hirsutism is the most common type of hirsutism.
It is felt to be due to increased conversion of testosterone into
its more active form, dihydrotestosterone or DHT. This conversion
occurs in peripheral tissues close to the hair follicles, and it is
mediated by the enzyme 5 alpha reductase.
[0015] Hirsutism may also be caused by conditions in which an
excess of androgens are synthesized by the ovaries, adrenal glands
or tumors.
[0016] Treatment of hirsutism depends in part on its cause. A
prudent search for a source of excess androgen production is
important to rule out androgen secreting tumors, ovarian disease
and other systemic hormonal abnormalities. In the setting of normal
menstruation and normal hormone levels, therapy for idiopathic
hirsutism can be instituted.
[0017] Readily available non-medical therapies for idiopathic
hirsutism include the plucking of hairs, waxing, electrolysis, and
depilatories. Medical therapies include various antiandrogenic
agents--such as synthetic progestins, dexamethesone, gonadotropin
releasing hormone agonists, ketoconazole, spironolactone, oral
contraceptives, and the antiandrogens cyproterone acetate and
flutamide. The topical agent Vaniqa has also been used. However,
unfortunately, none of the above therapies is free of undesirable
side effects.
[0018] As noted previously, SPBE has been shown to block 5 alpha
reductase, the enzyme that converts testosterone into
dihyrotestosterone or DHT. Saw palmetto berry extract also blocks
the binding of DHT to androgen receptors. Thus, in treating
hirsutism, SPBE is an effective agent and may act either by
blocking the formation of DHT, or by inhibiting binding of DHT to
the androgen receptors, or both without undue side effects.
PRIOR ART
[0019] U.S. Pat. No. 6,039,950 presents an extensive disclosure for
making pharmaceutical grade saw palmetto materials. The possible
use of SPBE in oral compositions for treating acne and hirsuitism
is noted as a possible future use. (col 7 line 66-col 8 line 3). No
actual data is presented. Numerous possible uses for the
medicament, Permixon, a purified form of SPPE, are suggested.
[0020] U.S. Pat. No. 6, 117,429 deals with reducing potential
adverse effects of androgenic testosterone precursors by
interfering with the production or the action of testosterone and
estrogen metabolites by use of nutrient combinations. Such
precursors enhance hormone responsive illness such as hirsuitism or
acne in women as an undesirable side effect. Saw palmetto berry is
listed as one of many natural agents which can be included in their
compositions to prevent the side effects caused by testosterone
precursors.
[0021] In both U.S. Pat. Nos. 6,039,950 and 6,117,429, the saw
palmetto berry composition is taken orally rather than comprising a
topical preparation pursuant to the present invention.
[0022] In U.S. Pat. No. Patent 6,225,299 Gibbs et al. describe the
use of gestogen and dienogest as antiandrogens to decrease sebum
production when used topically to control acne. They do not
describe the use of SPBE nor do they incorporate any
penetration-enhancing agents into their topical products. In fact
the preparations they describe contain potentially comedogenic or
acne causing substances such as peanut oil, castor oil, beeswax,
hardwax, lanolin, and paraffin.
[0023] In U.S. Pat. No. 6,174,892. Gormley, et al. describe the
treatment of acne with oral finasteride, a known 5 alpha reductase
inhibitor. They do not discuss the use of SPBE.
BRIEF DESCRIPTION OF THE INVENTION
[0024] The invention provides an improved preparation and a method
for treating acne and hirsuitism. A topically applied SPBE
formulation is hereby taught which offers efficacy and high
penetration into the hair follicles and sebaceous glands while
causing minimal irritation and side effects.
[0025] The preparation comprises an extract of saw palmetto berries
containing phytosterols and one or more non-irritating compounds to
enhance the penetration of the extract into the follicles and
sebaceous glands. More specifically, the improved low irritability
topical preparation comprises saw palmetto berry extract containing
phytosterols and one or more penetration enhancing constituents
selected from the group consisting of adapalene, tretinoin,
tretinoin gel microsponges, retinaldehyde, retinol, tazarotene,
salicylic acid, azelaic acid, and glycolic acid. Preferably the
penetration enhancing constituents consist of one member selected
from the group consisting of adapalene, tretinoin, tretinoin gel
microsponges, retinaldeyde and retinol, and another member selected
from the group consisting of salicylic acid and glycolic acid.
[0026] In another embodiment, the improved low irritability topical
preparation comprises an active saw palmetto berry extract
containing phytosterols, polyolprepolymer-2 and one or more
penetration enhancing constituents selected from the group
consisting of adapalene, tretinoin, tretinoin gel microsponges,
retinol, retinaldehyde, tazarotene, salicylic acid, azelaic acid,
and glycolic acid. Preferably the penetration enhancing
constituents consist of one member selected from the group
consisting of adapalene, tretinoin, tretinoin gel microsponges,
retinoldehyde and retinol, and another member selected from the
group consisting of salicylic acid and glycolic acid.
[0027] The preparations of the invention may include a vehicle
suitable for topical application to the face and/or trunk in the
form of a liquid, a gel, a foam, a cream, a lotion, a cleanser, or
a pad dampened with a liquid.
[0028] The method for the prevention of acne or hirsuitism
comprises applying to the affected areas a low irritability
preparation comprising a combination of an effective amount of a
saw palmetto berry extract containing phytosterols, and one or more
penetration enhancing constituents selected from the group
consisting of adapalene, tretinoin, tretinoin gel microsponges,
retinaldehyde, retinol, tazarotene, salicylic acid, azelaic acid,
and glycolic acid. In another embodiment, the method comprises
applying to affected areas a low irritability preparation
comprising saw palmetto berry extract containing phytosterols,
polyolprepolymer-2 and one or more penetration enhancing
constituents selected from the group consisting of adapalene,
tretinoin, tretinoin gel microsponges, retinaldehyde, retinol,
tazarotene, salicylic acid, azelaic acid, and glycolic acid.
[0029] The methods of applying the present SPBE compositions are
critical and are described below.
DETAILED DESCRIPTION OF THE INVENTION
[0030] The present invention provides low irritability topically
applied formulations of SPBE offering enhanced effectiveness in
treating and preventing acne and hirsuitism by their greater
ability to penetrate the hair follicles and sebaceous glands of the
face and trunk. In addition, there is provided by the invention a
method for controlling acne and hirsutism by application to the
face, trunk and other affected areas of a preparation comprised of
the improved formulations.
[0031] The method of application of the SPBE formulation is
critical to the effectiveness of the invention. Important variables
include the vehicle chosen, and the frequency and duration of
application of the product.
[0032] This invention is described by a number of formulations and
vehicles. Each vehicle is suited for use on a different type of
skin. Alcohol based solutions and pads should be used on oily skin.
They will help to remove unwanted excess oil from the skin without
adding additional moisture. These would be well suited for use on
the face of persons with acne or a combination of acne and
hirsutism. In contrast, a lotion or cream should be used on dry or
less oily skin. These vehicles will serve to moisturize the skin
and protect it from irritation. Gels are perhaps most suitable for
oily skin, but are reasonable to use on all skin types. They are
also ideal to use over large hair bearing areas as they rub in
well. Gels are particularly appropriate for use on acne prone
chests, shoulders and upper backs. Similarly, foams which
volatilize easily are excellent to use on large hair bearing
areas.
[0033] Initially, all product formulations should be applied once
daily. After two weeks, in the absence of allergy or irritation,
the frequency of application should be increased to twice daily.
All formulations should be applied after washing with a mild soap,
but before the use of moisturizers, sunscreens or makeups.
[0034] Improvement should be noted in the treatment of facial acne
within approximately one month. Additional improvement should
continue for four or more months. Responses on the trunk may take
longer because of thicker skin in these areas and slower
penetration of the products into hair follicles.
[0035] Responses in hirsutism will be slower than in acne because
of the growth pattern of hairs. Only after the large unwanted
terminal hairs that characterize hirsutism have completed their
growth cycle and fallen out, will meaningful improvement be seen.
These large hairs will then be replaced by tiny, light, barely
visible vellus hairs. Such improvement should be noted after four
to six months.
[0036] Once a steady state has been readied and no additional
improvements is noted in the acne or hirsutism, application of the
invention can be decreased to once daily. This should occur after
approximately four months in the case of acne and six to eight
months in the treatment of hirsutism. In some instances, every
other day therapy may prove adequate for a maintenance regimen.
[0037] This invention describes SPBE in conjunction with several
penetration enhancing agents. Thus, using this invention will not
only increase the penetration of SPBE into hair follicles, but it
will increase the penetration of other topically applied agents as
well. This should increase the effectiveness of these agents. It is
critical that the invention be applied appropriately with respect
to these other agents so as to maximize the effectiveness of all
products used.
[0038] Topical medication for the treatment of acne include washes,
pads, solutions, gels, lotions and creams. There is currently only
one prescription provided for the treatment of hirsutism. It is
known as Vaniqa, and it is a cream. None of these approved
treatments acts by interfering with the conversion of testosterone
to DHT nor with the binding of DHT to androgen receptors. All of
these medications should therefore work synergistically with the
invention.
[0039] When used in a cream or lotion vehicle, this invention
should be applied after the use of a wash, pad, solution or gel
formulation of a different type of product.
[0040] When used as a gel or foam, it should be applied after
washes, pads or solutions of another type-of product, and before
any other creams or lotions.
[0041] When used as a solution, the SPBE product should be used
after washes or pads of another product, but before any other gels,
lotions or creams.
[0042] SPBE pads should be used before solutions, gels, lotions or
creams of another product. The pads, however, should not be used
for a minimum of one hour after a wash or a pad formulation of
another product has been used. Doing so may remove some of the
active ingredient of that other product from the skin.
[0043] When used in a vehicle similar to the vehicle of another
product, the SPBE product can be used before, with, or after that
other product.
[0044] The following table describes when to apply the present
invention in relation to other medicated skin products, eg. before
or after
1 Application Order Relative to Unrelated Medicated Product Vehicle
Methods of Applying SPBE Vehicle wash pad Solution gel lotion/cream
pad Before before before solution after after no before before
preference gel after after After no preference before foam after
after After no preference before lotion/cream after after After
after no preference
[0045] By way of summary, all product formulations are applied at
least once daily after washing with mild soap, but before use of
moisturizers, sunscreens or makeup. In the absence of allergy or
irritation, the frequency of application is increased to twice
daily. Improvement in facial acne typically occurs in one month.
Improvement may continue for four or more months.
Amount Needed/application
[0046] A minimum concentration of purified SPBE of approximately
0.5 weight percent in the preparation is applied to the skin. This
could be created, for example, by mixing 0.5 grams of 85%-95%
purified SPBE as manufactured by the Saw Palmetto Harvesting
Company in Frostproof, Fla., with 99.5 grams of vehicle.
Preferably, the concentration of SPBE should be 1.0 weight percent
or higher. Most preferably, the concentration of SPBE should be 2.0
weight percent or higher.
[0047] In order to treat an area the size of a typical face,
approximately 1 cc to 2 cc of solution or lotion, and 1 to 2 grams
of gel or cream are required per application.
[0048] Response in treating hirsutism is slower and may require
four to six months of treatment.
[0049] In both cases once a steady state has been reached and no
further improvement is noted, application of the present
composition may be reduced to once daily. Typically this is four
months in the case of acne and six to eight months in the treatment
of hirsutism.
[0050] The SPBE constituent of the preparation of the invention may
be obtained from a number of commercial sources. Satisfactory
non-irritating SPBEs include Permixon.RTM. from P.F. Medicaments,
Paris, France, SPBE from McZand Herbal Inc., Santa Monica, Calif.,
and others.
[0051] In a preferred embodiment of the preparation of the present
invention, the SPBE constituent is the alcohol soluble material
sold by Saw Palmetto Harvesting Company, Frostproof Fla. This SPBE
is non-irritating when applied to the scalp. Typically, it has the
following major components and concentrations:
2 Phytosterols capesterol about 0.01 to about 0.1 wt. wt. %
beta-sitosterol about 0.1 to about 0.4 wt. % stimasterol about 0.01
to about 0.1 wt. % Total sterols greater than about 0.15 wt. %
Fatty Acids caprylic about 1.0 to about 3.0 wt. % capric about 1.0
to about 3.0 wt. % lauric about 25 to about 32 wt. % cis-linoleic
about 3.0 to about 5.0 wt. % linolenic about 0.5 to about 1.5 wt. %
myristic about 10 to about 15 wt. % oleic about 26 to about 35 wt.
% palmitic about 7 to about 11 wt. % stearic about 1.0 to about 2.0
wt. %
[0052] Other phytosterols, other fatty acids and other minor
components may also be present without effecting the utility of the
SPBE. The phytosterols are believed to be the active agents in the
SPBE.
[0053] In another embodiment of the preparation of the present
invention, all or a portion of the fatty acids have been removed
from the above composition by further purification, as for example
by extraction with aqueous alkaline solution. In this embodiment,
the phytosterol composition of the SPBE is as follows: 1
Phytosterols _ capesterol greater than about 0.02 wt . %
beta-sitosterol greater than about 0.2 wt . % stimasterol greater
than about 0.02 wt . % Total sterols greater than about 0.3 wt .
%
[0054] The preparation of the invention comprises the SPBE and one
or more penetration enhancing constituents selected from the group
consisting of adapalene, tretinoin, tretinoin gel microsponges,
retinol, retinaldehyde, tazarotene, salicylic acid, azelaic acid,
and glycolic acid. In another embodiment, the preparation of the
invention comprises the SPBE, polyolprepolymer-2 and one or more
penetration enhancing constituents selected from the group
consisting of adapalene, tretinoin, tretinoin gel microsponges,
retinol, retinaldehyde, tazarotene, salicylic acid, azelaic acid,
and glycolic acid.
[0055] Adapalene is a synthetic retinoid manufactured by Galderma
having the following structural formula: 1
[0056] A research article by B. Shroot, "Pharmacodynamics and
Pharmacokinetics of Topical Adapalene", Journal of the American
Academy of Dermatology, S17-S24, (1998) has shown that adapalene
has several useful properties. First, adapalene has significant
comedolytic activity, i.e., it opened comedones or clogged pores.
In the preparation of the invention, adapalene acts to enhance the
effectiveness of the SPBE. Second, a 0.1 wt. % adapalene gel had a
low irritative potential only slightly greater than petroleum jelly
used as a control. Third, adapalene has anti-inflammatory effects
both in vitro and in vivo. Each of these documented properties
provides superiority to the preparations of the invention over the
SPBE formulations of the prior art. Lastly, as adapalene is a
retinoid, it may be expected to have direct benefits on stimulating
hair regrowth.
[0057] Adapalene is present in a preparation of the invention in a
concentration from about 0.01 wt. % to about 1wt. %. Preferably,
the adapalene concentration is from about 0.05 wt. % to about 0.5
wt. %. Most preferably, the adapalene concentration is about 0.1
wt. %.
[0058] Tazarotene is a retinoid having the following structural
formula: 2
[0059] Pharmacologically, tazarotene normalizes keratinocyte
differentiation and minimizes proliferation of keratinocytes. These
actions serve to inhibit microcomedo formation and prevent
follicular plugging. Tazarotene also decreases epidermal
inflammation and has been shown to down-regulate biochemical
markers of inflammation. In the preparation of the invention,
tazarotene acts to enhance the effectiveness of the SPBE.
[0060] Tazarotene is present in a preparation of the invention in a
concentration from about 0.01 wt. % to about 1 wt. %. Preferably,
the tazarotene concentration is from about 0.02 wt. % to about 0.2
wt. %. Most preferably, the tazarotene concentration is about 0.05
to 0.1 wt. %.
[0061] Tretinoin has been used in acne therapy. Tretinoin is
all-trans retinoic acid, also known as (all E)
3,7-dimethyl-9-(2,6,6-trimethyl-1-cy-
lclohexen-1-yl)-2,4,6,8,-nonatetraenoic acid having the following
structural formula: 3
[0062] Tretinoin inhibits comedo formation and enhances
comedolysis. Thus, it acts to prevent pores from becoming clogged
and enhances removal of debris from clogged pores. There is also
evidence that tretinoin itself increases hair growth factors. While
tretinoin has an irritating potential, it has been found that a
0.025 wt. % tretinoin cream is equivalent in irritation to a 0.1
wt. % adapalene gel. Additionally, a new form of topical tretinoin,
RETIN-A MICRO.RTM., has become available from Ortho Dermatological,
Raritan N. J. in which 0.1 wt. % of tretinoin is entrapped in a
microscopic particle termed a "microsponge". This particle
localizes to the follicle after topical application and then
releases tretinoin. The slow release minimizes irritation. By
virtue of their increased effectiveness and low irritation
potential, a preparation of the invention containing tretinoin in
the form of gel microsponges is superior to SPBE preparations of
the prior art. Tretinoin is present in a preparation of the
invention in a concentration from about 0.005 wt. % to about 0.2
wt. %. Preferably tretinoin concentration is from about 0.025 wt. %
to about 0.1 wt. %.
[0063] Retinaldehyde is the aldehyde analog of retinoic acid having
a terminal aldehyde group in place of the carboxyl group of
retinoic acid. It has been shown by J. W. Fluhr et al, Dermatology,
199, Suppl 1( ):57-60 (1999) that retinaldehyde is significantly
less irritating than retinoic acid (tretinoin). It is expected to
be equally as effective in increasing the absorption of SPBE as is
tretinoin. Incorporation of retinaldehyde in the SPBE preparations
of the invention provides superior effectiveness and lower
irritation potential of these preparations over the SPBE
formulations of the prior art. Retinaldehyde is present in a
preparation of the invention in a concentration from about 0.01 wt.
% to about 1.0 wt. %. Preferably the retinaldehyde concentration is
from about 0.05 wt. % to about 0.5 wt. %. Most preferably, the
retinaldehyde concentration is about 0.1 wt. %.
[0064] All trans retinol, or retinol, is a component of numerous
over-the-counter skin care products. Like tretinoin, or all trans
retinoic acid, topical retinol increases the expression of retinoic
acid binding proteins on keratinocytes. It also stimulates
hyperplasia of healthy epidermal tissue much the way tretinoin
does. Some in fact hypothesize that retinol is a precursor of
tretinoin. Further, retinol has been shown to cause less cutaneous
irritation than tretinoin. In this invention, retinol is used to
enhance the penetration of SPBE into follicle and sebaceous glands.
Retinol is present in the invention in a concentration from about
0.01 wt % to 2.0 wt %. Preferably, the concentration is between
0.5% wt % and 1.5 wt %. Most preferably, the concentration is 1.0
wt %.
[0065] Azelaic acid, also known as 1,7 heptanedicarboxylic acid has
the formula:
HOOC--(CH.sub.2)).sub.7----COOH
[0066] This agent has been shown to have antibacterial,
antikeratinizing and anti-inflammatory properties. Thus, its use
leads to a reduction in thickness of the strateum corneum or top
layers of the skin, while preventing the formation of
microcomedones or plugged follicles. These effects allow for
increased penetration of SPBE into follicles while causing little,
if any irritation. Azeleic acid has been shown to cause less
irritation than tretinoin. Incorporation of azeleic acid in the
SPBE preparations of the invention provides superior effectiveness
and lower irritation potential of these preparations over the SPBE
formulations of the prior art.
[0067] Azeleic acid is present in a preparation of the invention in
a concentration from about 0.1 wt. % to about 40 wt. %. Preferably,
the azeleic acid concentration is about 20 wt. %.
[0068] Alpha hydroxy acids have been shown to exfoliate the stratum
corneum. In the present compositions, alpha hydroxy acids act to
enhance the effectiveness of SPBE by increasing its penetration
into the skin. Glycolic acid, a naturally occurring .alpha.alpha
hydroxy acid, has the formula: HO--CH.sub.2--COOH. Glycolic acid,
or another alpha hydroxy acid, could be incorporated into the
preparations of the invention. Glycolic acid is present in the
present preparations in a concentration from about 0.1 wt. % to
about 20 wt. %. Preferably, the glycolic acid concentration is from
about 0.5 wt. % to about 10 wt. %. Most preferably, the glycolic
acid concentration is about 5 wt. %.
[0069] It has been shown by M. C. Spellman et al, Clinical Therapy,
20(4), 711-721 (1998) that a combination of azelaic acid and
glycolic acid was less irritating than tretinoin and equally as
effective in treating facial acne. As both azeleic acid and
glycolic acid lead to a reduction in the thickness of the stratum
corneum, and both have anti-inflammatory properties, this
combination increases the absorption of topically applied SPBE
while causing less irritation than the prior art. Incorporation of
azelaic acid and glycolic acid in the SPBE preparations of the
invention provides superiority of these preparations over the SPBE
formulations of the prior art.
[0070] Azelaic and glycolic acids are present in a preparation of
the invention in relative proportions ranging from about 10:90
azelaic:glycolic to about 90:10 azelaic:glycolic. The total
concentration of azelaic plus glycolic acids in a preparation of
the invention is from about 0.1 wt. % to about 40 wt. %.
Preferably, the azelaic plus glycolic acid concentration is about
20 wt %.
[0071] Salicylic acid (2-hydroxy benzoic acid) is a beta hydroxy
acid having the formula:
OH--C.sub.6H.sub.4--COOH
[0072] Beta hydroxy acids are used topically in Salicylic acid, in
numerous products to reduce scaling. A beta hydroxy acid, is well
known as a keratolytic and has been used in combination with
glycolic acid to aid in comedolysis or the opening of clogged
follicles. It increases the penetration of SPBE into follicles and
has a low irritancy potential. Incorporation of beta hydroxy acids,
in general, and particular salicylic acid in the SPBE preparations
of the invention provides superiority of these preparations over
the SPBE formulations of the prior art.
[0073] Salicyclic acid or other beta hydroxy acid are presented in
the instant preparations in a concentration from about 0.1 wt. % to
about 10 wt. %. Preferably, the salicyclic acid concentration is
between about 1% wt. % and 3 wt %.
[0074] Polyolprepolymer-2 is a urethane compound of molecular
weight up to about 200,000 prepared by reacting approximately two
moles of a hydroxy terminated linear alkylene or polyalkylene
glycol or polyether with approximately one mole of a monomeric
organic diisocyanate as described in U.S. Pat. No. 5,700,483 herein
incorporated by reference in its entirety. Preferably,
polyolprepolymer-2 is of average molecular weight of about 4000 and
is prepared by reacting about one mole of
dicyclohexylmethanediisocyanate with about two moles of propylene
glycol 725.
[0075] Incorporation of polyolprepolymer-2 in a topical formulation
has been shown to have the characteristic of moderating the rate of
transmission of a retinoid to the skin. Specifically, it has been
shown that formulations incorporating tretinoin and
polyolprepolymer-2 are significantly less irritating and yet
therapeutically equally as effective compared to formulations
identical except for the absence of the polyolprepolymer-2. When
polyolprepolymer-2 is present in a preparation of the invention,
tretinoin need not be in the form of gel microsponges.
Incorporation of the polyolprepolymer-2 in the SPBE preparations of
the invention provides superiority of these preparations over the
SPBE formulations of the prior art. The polyolprepolymer-2 is
present in a preparation of the invention in a concentration from
about 1 wt % to about 20 wt %. Preferably, the polyolprepolymer-2
is present in a concentration from about 2 wt % to about 15 wt
%.
[0076] The preparations of the invention may include a vehicle for
the application to the scalp in the form of a liquid, a gel, a
foam, a cleanser or a pad dampened with a liquid. Preferably the
SPBE preparations of the invention are employed as a liquid or a
gel. Most preferred is a gel.
[0077] The formulation of all such topical vehicles is well known
to those skilled in the art. A suitable topical vehicle for
formulation of the SPBE preparation as a liquid includes ethanol,
isopropanol, their mixtures in all proportions. To prepare a liquid
preparation of the invention, the SPBE and the penetration
enhancing constituents are dissolved or dispersed in the alcohol
constituents with agitation. Elevated temperatures may be used to
facilitate the dispersion process.
[0078] An example of a suitable topical vehicle for formulation of
the SPBE preparation as a gel is:
3 Component wt % hydroxypropylcellulose 2.1 70/30 isopropyl
alcohol/water 90.9 propylene glycol 5.1 Polysorbate 80 1.9
[0079] To prepare a gel preparation of the invention, the 70%
isopropanol and the propylene glycol are first combined. The SPBE
and the penetration enhancing constituents are dispersed in the
alcohols with agitation. The hydroxypropylcellulose and the
Polysorbate 80 are then incorporated with mixing until a gel
results.
[0080] An example of a suitable topical vehicle formulation for
formulation of the SPBE preparation as a foam is:
4 Component wt % cetyl alcohol 1.1 stearyl alcohol 0.5 Quaternium
52 (52%) 1.0 propylene glycol 2.0 Ethanol 95 PGF3 61.05 deionized
water 30.05 P75 hydrocarbon propellant 4.30
[0081] To prepare a foam preparation of the invention, the SPBE and
the penetration enhancing constituents are first dispersed in the
ethanol at elevated temperature. The cetyl and stearyl alcohols are
added to the heated dispersion and mixed until dissolved. The
Quaternium 52, the propylene glycol and water are added and stirred
until homogeneous while maintaining elevated temperature. The
mixture is cooled and dispensed into an aerosol can. A valve is
fitted to the can and the can is then charged with the
propellant.
[0082] The mode of use of a SPBE preparation of the invention is
application of 1 cc of the preparation to the affected area of face
twice a day for a period of four months. Two cc of the preparation
are needed for large areas of the trunk. The preparation should be
massaged into the skin or allowed to dry on the skin and remain in
place for at least four hours before washing, rinsing or showering.
After the four month initial period, a sustaining application of 1
cc once a day is used.
[0083] The following examples are presented to provide a more
complete understanding of the invention. The specific techniques,
conditions, materials, and proportions set forth to illustrate the
principles and practice of the invention are exemplary and should
not be construed as limiting the scope of the invention.
EXAMPLES
Examples 1-14
[0084] Tables I and II below provide examples of preparations of
the invention. The SPBE in this table is provided by Saw Palmetto
Harvesting Company, Frostproof, Fla. and has a phytosterol
concentration of 0.16 wt. %. The topical vehicle may be chosen
appropriate to the use of the preparation as a liquid gel, a foam,
a cleanser, or a pad dampened with a liquid. All percentages are by
weight.
5TABLE I Constituent - % Ex. 1 Ex. 2 Ex. 3 Ex. 4 Ex. 5 Ex. 6 Ex. 7
Ex. 8 SPBE 31.25 40.0 60.0 80.0 31.25 31.25 31.25 31.25 Adapalene
0.1 -- -- -- -- -- -- glycolic acid -- 5.0 -- -- -- -- -- tretinoin
gel or -- -- 0.025 -- -- -- -- tretinoin gel micro-sponges
Retinaldehyde -- -- -- 0.1 -- -- -- azelaic acid -- -- -- -- 20 --
-- tazarotene, -- -- -- -- -- 0.1 -- salicylic acid, -- -- -- -- --
-- 2.0 retinol 1.0 Topical B B B B B B B B Vehicle B stands for
Balance of the Composition
[0085]
6TABLE II Constituent - % Ex. 9 Ex. 10 Ex. 11 Ex. 12 Ex. 13 Ex. 14
Ex. 15 Ex. 16 SPBE 31.25 31.25 31.25 31.25 31.25 31.25 31.25 31.25
Adapalene 0.05 0.05 -- -- -- glycolic acid 5.0 -- 1.0 5.0 -- 5.0
5.0 2.0 tretinoin -- -- 0.025 0.1 -- 0.05 Retinaldehyde -- -- 0.1
-- -- azelaic acid -- -- -- 15 10 -- Tazarotene -- -- -- -- -- 0.1
salicylic acid -- 2.0 -- -- -- -- polyolprepolymer-2 10 10 10 10 10
10 10 10 retinol 1.0 Topical Vehicle B B B B B B B B
[0086] B Stands for Balance of the Composition
Examples 15-21
[0087] Table III below provides examples of preparations of the
invention. The SPBE in this table has been purified from the SPBE
provided by Saw Palmetto Harvesting Company, Frostproof, Fla. by
extraction with an aqueous alkaline solution and has a phytosterol
concentration of 0.5 wt %. The topical vehicle may be chosen
appropriate to the use of the preparation as a liquid, a gel, a
foam, a wash or a pad dampened with a liquid. All percentages are
by weight.
7TABLE III Constituent - % Ex. 17 Ex. 18 Ex. 19 Ex. 20 Ex. 21 Ex.
22 Ex. 23 Ex. 24 SPBE 15.0 20.0 30.0 10.0 10.0 10.0 10.0 10.0
Adapalene 0.05 0.05 -- -- -- glycolic acid 5.0 -- 1.0 5.0 -- 5.0
5.0 2.0 Tretinoin -- -- 0.025 -- 0.05 -- retinaldehyde -- -- .1 --
-- retinol 1.0 azelaic acid -- -- -- 15 10 -- -- Tazarotene -- --
-- -- -- 0.1 -- salicylic acid -- 2.0 -- -- -- -- --
polyolprepolymer-2 10 10 10 10 10 10 10 Topical Vehicle B B B B B B
B
[0088] B Stands for Balance of the Composition
[0089] Various modifications may be made to the present invention,
such as the use of the penetrating enhancing agents incorporated in
the SPBE compositions.
[0090] The scope of the present invention is set forth in the
following claims.
* * * * *