U.S. patent application number 09/873159 was filed with the patent office on 2002-03-07 for cosmetic compositions containing substituted iminodibenzyl or fluorene derivatives.
This patent application is currently assigned to Unilever Home & Personal Care USA, Division of Conopco, Inc.. Invention is credited to Bajor, John Steven, Pocalyko, David Joseph.
Application Number | 20020028804 09/873159 |
Document ID | / |
Family ID | 22803819 |
Filed Date | 2002-03-07 |
United States Patent
Application |
20020028804 |
Kind Code |
A1 |
Bajor, John Steven ; et
al. |
March 7, 2002 |
Cosmetic compositions containing substituted iminodibenzyl or
fluorene derivatives
Abstract
Cosmetic methods and compositions containing selected
iminodibenzyl or fluorene derivatives. When used for skin or hair
care, the inventive compositions provide control of sebum secretion
from sebocytes, improved oil control and improved feel, and prevent
shine and stickiness.
Inventors: |
Bajor, John Steven; (Ramsey,
NJ) ; Pocalyko, David Joseph; (Wayne, NJ) |
Correspondence
Address: |
UNILEVER
PATENT DEPARTMENT
45 RIVER ROAD
EDGEWATER
NJ
07020
US
|
Assignee: |
Unilever Home & Personal Care
USA, Division of Conopco, Inc.
|
Family ID: |
22803819 |
Appl. No.: |
09/873159 |
Filed: |
June 1, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60215648 |
Jun 30, 2000 |
|
|
|
Current U.S.
Class: |
514/217 ;
424/401 |
Current CPC
Class: |
A61K 8/4906 20130101;
A61Q 19/00 20130101; A61K 8/42 20130101; A61Q 19/008 20130101; A61K
8/69 20130101 |
Class at
Publication: |
514/217 ;
424/401 |
International
Class: |
A61K 007/00; A61K
031/55 |
Claims
What is claimed is:
1. A cosmetic composition comprising: (i) from about 0.001% to
about 50% of a substituted iminodibenzyl compound 37or a
substituted fluorine compound 38selected from the group consisting
of compounds A through H as follows:
20 Compound R Complete Structure A 39 40 B 41 42 C 43 44 D 45 46 E
47 48 F 49 50 G 51 52 H 53 54
and (ii) a cosmetically acceptable vehicle.
2. The composition of claim 1 further comprising a retinoid.
3. A method of reducing or preventing oily skin conditions, the
method comprising applying to the skin the composition of claim
1.
4. A cosmetic method of reducing or preventing sebum secretion from
sebocytes, the method comprising applying to the skin the
composition of claim 1.
Description
FIELD OF THE INVENTION
[0001] Cosmetic methods and compositions containing iminodibenzyl
or fluorene derivatives.
BACKGROUND OF THE INVENTION
[0002] A frequent, undesirable skin condition is "oily skin," the
condition which results from the excessive amount of sebum on the
skin. Sebum is skin oil which is produced by sebocytes (cells of
the sebaceous glands in the skin) and is then secreted to the skin
surface. Oily skin is associated with a shiny, undesirable
appearance and a disagreeable tactile sensation. Oily skin affects
various age groups. Cosmetic products which provide sebum control
are highly desirable.
SUMMARY OF THE INVENTION
[0003] The present invention includes, in its first aspect, a
cosmetic composition comprising:
[0004] (i) from about 0.001% to about 50% of a substituted
iminodibenzyl compound 1
[0005] or a substituted fluorine compound 2
[0006] selected from the group consisting of compounds A through H
as follows:
1 Compound R Complete Structure A 3 4 B 5 6 C 7 8 D 9 10 E 11 12 F
13 14 G 15 16 H 17 18
[0007] and
[0008] (ii) a cosmetically acceptable vehicle.
[0009] The present invention also includes a method of controlling
or preventing an oily skin condition, especially in the facial
area, by applying to the skin the inventive composition.
[0010] The invention also includes a cosmetic method of reducing,
preventing or controlling sebum secretion from sebocytes by
applying to the skin the inventive composition.
DETAILED DESCRIPTION OF THE INVENTION
[0011] Except in the operating and comparative examples, or where
otherwise explicitly indicated, all numbers in this description
indicating amounts of material or conditions of reaction, physical
properties of materials and/or use are to be understood as modified
by the word "about." All amounts are by weight of the oil-in-water
emulsion, unless otherwise specified.
[0012] Cosmetic compositions within the scope of the invention are
generally personal care compositions including but not limited to
skin care compositions (leave-on or rinse-off), hair care
compositions (shampoos and conditioners and hair tonics),
dentifrices (toothpastes and mouthwashes), and lipsticks and color
cosmetics. Inventive compositions may be in the form of lotions,
creams, gels, soap bars, shower gels, toners, and face masks.
[0013] The preferred compositions are skin care compositions, in
order to deliver anti-sebum benefit to the skin.
[0014] The term "skin" as used herein includes the skin on the
face, neck, chest, back, arms, hands, legs and scalp.
[0015] The inventive methods and compositions include the
substituted iminodibenzyl compound 19
[0016] or
[0017] a substituted fluorine compound 20
[0018] selected from the group consisting of compounds A through H
as follows:
2 Compound R Complete Structure A 21 22 B 23 24 C 25 26 D 27 28 E
29 30 F 31 32 G 33 34 H 35 36
[0019] The substituted iminodibenzyl or fluorine compounds are
employed in the present invention in an amount of from 0.0001% to
50%, preferably from 0.0001% to 10%, most preferably from 0.0001%
to 5%.
[0020] The substituted iminodibenzyl or fluorine compounds can be
obtained from New Chemical Entities, Inc. (Bothell, Wash.).
[0021] The compositions according to the invention comprise a
cosmetically acceptable vehicle to act as a diluant, dispersant or
carrier for the substituted iminodibenzyl or fluorine compounds in
the composition, so as to facilitate its distribution when the
composition is applied to the substrate.
[0022] The vehicle may be aqueous, anhydrous or an emulsion.
Preferably, the compositions are aqueous or an emulsion, especially
water-in-oil or oil-in-water emulsion. Water when present will be
in amounts which may range from 5 to 99%, preferably from 40 to
90%, optimally between 60 and 90% by weight.
[0023] Besides water, relatively volatile solvents may also serve
as carriers within compositions of the present invention. Most
preferred are monohydric C.sub.1-C.sub.3 alkanols. These include
ethyl alcohol, methyl alcohol and isopropyl alcohol. The amount of
monohydric alkanol may range from 1 to 70%, preferably from 10 to
50%, optimally between 15 and 40% by weight.
[0024] Emollient materials may also serve as cosmetically
acceptable carriers. These may be in the form of silicone oils and
synthetic esters. Amounts of the emollients may range anywhere from
0.1 to 50%, preferably between 1 and 20% by weight.
[0025] Silicone oils may be divided into the volatile and
non-volatile variety. The term "volatile" as used herein refers to
those materials which have a measurable vapor pressure at ambient
temperature. Volatile silicone oils are preferably chosen from
cyclic or linear polydimethylsiloxanes containing from 3 to 9,
preferably from 4 to 5, silicon atoms. Linear volatile silicone
materials generally have viscosities less than about 5 centistokes
at 25.degree. C. while cyclic materials typically have viscosities
of less than about 10 centistokes. Nonvolatile silicone oils useful
as an emollient material include polyalkyl siloxanes, polyalkylaryl
siloxanes and polyether siloxane copolymers. The essentially
non-volatile polyalkyl siloxanes useful herein include, for
example, polydimethyl siloxanes with viscosities of from about 5 to
about 25 million centistokes at 25.degree. C. Among the preferred
non-volatile emollients useful in the present compositions are the
polydimethyl siloxanes having viscosities from about 10 to about
400 centistokes at 25.degree. C.
[0026] Among the ester emollients are:
[0027] (1) Alkenyl or alkyl esters of fatty acids having 10 to 20
carbon atoms. Examples thereof include isoarachidyl neopentanoate,
isononyl isonanonoate, oleyl myristate, oleyl stearate, and oleyl
oleate.
[0028] (2) Ether-esters such as fatty acid esters of ethoxylated
fatty alcohols.
[0029] (3) Polyhydric alcohol esters. Ethylene glycol mono and
di-fatty acid esters, diethylene glycol mono- and di-fatty acid
esters, polyethylene glycol (200-6000) mono- and di-fatty acid
esters, propylene glycol mono- and di-fatty acid esters,
polypropylene glycol 2000 monooleate, polypropylene glycol 2000
monostearate, ethoxylated propylene glycol monostearate, glyceryl
mono- and di-fatty acid esters, polyglycerol poly-fatty esters,
ethoxylated glyceryl monostearate, 1,3-butylene glycol
monostearate, 1,3-butylene glycol distearate, polyoxyethylene
polyol fatty acid ester, sorbitan fatty acid esters, and
polyoxyethylene sorbitan fatty acid esters are satisfactory
polyhydric alcohol esters.
[0030] (4) Wax esters such as beeswax, spermaceti, myristyl
myristate, stearyl stearate and arachidyl behenate.
[0031] (5) Sterols esters, of which cholesterol fatty acid esters
are examples thereof.
[0032] Fatty acids having from 10 to 30 carbon atoms may also be
included as cosmetically acceptable carriers for compositions of
this invention. Illustrative of this category are pelargonic,
lauric, myristic, palmitic, stearic, isostearic, hydroxystearic,
oleic, linoleic, ricinoleic, arachidic, behenic and erucic
acids.
[0033] Humectants of the polyhydric alcohol type may also be
employed as cosmetically acceptable carriers in compositions of
this invention. The humectant aids in increasing the effectiveness
of the emollient, reduces scaling, stimulates removal of built-up
scale and improves skin feel. Typical polyhydric alcohols include
glycerol, polyalkylene glycols and more preferably alkylene polyols
and their derivatives, including propylene glycol, dipropylene
glycol, polypropylene glycol, polyethylene glycol and derivatives
thereof, sorbitol, hydroxypropyl sorbitol, hexylene glycol,
1,3-butylene glycol, 1,2,6-hexanetriol, ethoxylated glycerol,
propoxylated glycerol and mixtures thereof. For best results the
humectant is preferably propylene glycol or sodium hyaluronate. The
amount of humectant may range anywhere from 0.5 to 30%, preferably
between 1 and 15% by weight of the composition.
[0034] Thickeners may also be utilized as part of the cosmetically
acceptable carrier of compositions according to the present
invention. Typical thickeners include crosslinked acrylates (e.g.
Carbopol 982), hydrophobically-modified acrylates (e.g. Carbopol
1382), cellulosic derivatives and natural gums. Among useful
cellulosic derivatives are sodium carboxymethylcellulose,
hydroxypropyl methylcellulose, hydroxypropyl cellulose,
hydroxyethyl cellulose, ethyl cellulose and hydroxymethyl
cellulose. Natural gums suitable for the present invention include
guar, xanthan, sclerotium, carrageenan, pectin and combinations of
these gums. Amounts of the thickener may range from 0.0001 to 5%,
usually from 0.001 to 1%, optimally from 0.01 to 0.5% by
weight.
[0035] Collectively, the water, solvents, silicones, esters, fatty
acids, humectants and/or thickeners will constitute the
cosmetically acceptable carrier in amounts from 1 to 99.9%,
preferably from 80 to 99% by weight.
[0036] An oil or oily material may be present, together with an
emulsifier to provide either a water-in-oil emulsion or an
oil-in-water emulsion, depending largely on the average
hydrophilic-lipophilic balance (HLB) of the emulsifier
employed.
[0037] Surfactants may also be present in cosmetic compositions of
the present invention. Total concentration of the surfactant will
range from 0.1 to 40%, preferably from 1 to 20%, optimally from 1
to 5% by weight of the composition. The surfactant may be selected
from the group consisting of anionic, nonionic, cationic and
amphoteric actives. Particularly preferred nonionic surfactants are
those with a C.sub.10-C.sub.20 fatty alcohol or acid hydrophobe
condensed with from 2 to 100 moles of ethylene oxide or propylene
oxide per mole of hydrophobe; C.sub.2-C.sub.10 alkyl phenols
condensed with from 2 to 20 moles of alkylene oxide; mono- and di-
fatty acid esters of ethylene glycol; fatty acid monoglyceride;
sorbitan, mono- and di- C.sub.8-C.sub.20 fatty acids; block
copolymers (ethylene oxide/propylene oxide); and polyoxyethylene
sorbitan as well as combinations thereof. Alkyl polyglycosides and
saccharide fatty amides (e.g. methyl gluconamides) are also
suitable nonionic surfactants.
[0038] Preferred anionic surfactants include soap, alkyl ether
sulfate and sulfonates, alkyl sulfates and sulfonates, alkylbenzene
sulfonates, alkyl and dialkyl sulfosuccinates, C.sub.8-C.sub.20
acyl isethionates, acyl glutamates, C.sub.8-C.sub.20 alkyl ether
phosphates and combinations thereof.
[0039] Various types of additional active ingredients may be
present in cosmetic compositions of the present invention. Actives
are defined as skin benefit agents other than emollients and other
than ingredients that merely improve the physical characteristics
of the composition. Although not limited to this category, general
examples include additional anti-sebum ingredients and
sunscreens.
[0040] Sunscreens include those materials commonly employed to
block ultraviolet light. Illustrative compounds are the derivatives
of PABA, cinnamate and salicylate. For example, avobenzophenone
(Parsol 1789.RTM.) octyl methoxycinnamate and 2-hydroxy-4-methoxy
benzophenone (also known as oxybenzone) can be used. Octyl
methoxycinnamate and 2-hydroxy-4-methoxy benzophenone are
commercially available under the trademarks, Parsol MCX and
Benzophenone-3, respectively. The exact amount of sunscreen
employed in the compositions can vary depending upon the degree of
protection desired from the sun's UV radiation.
[0041] A preferred additional anti-sebum agent is a retinoid. It
has been found that compounds E through H had improved sebum
suppressive activity in the presence of a retinoid. Retinoids (e.g.
retinol/retinyl ester/retinal/retinoic acid) are present in the
epidermis, so compounds E through H will have the improved sebum
suppressive activity when applied to the skin. The preferred
compositions, however, include a retinoid as an additional
ingredient.
[0042] The term "retinol" includes the following isomers of
retinol: all-trans-retinol, 13-cis-retinol, 11 -cis-retinol,
9-cis-retinol, 3,4-didehydro-retinol. Preferred isomers are
all-trans-retinol, 13-cis-retinol, 3,4-didehydro-retinol,
9-cis-retinol. Most preferred is all-trans-retinol, due to its wide
commercial availability.
[0043] Retinyl ester is an ester of retinol. The term "retinol" has
been defined above. Retinyl esters suitable for use in the present
invention are C 1-C 30 esters of retinol, preferably C 2-C 20
esters, and most preferably C 2, C 3, and C 16 esters because they
are more commonly available. Examples of retinyl esters include but
are not limited to: retinyl palmitate, retinyl formate, retinyl
acetate, retinyl propionate, retinyl butyrate, retinyl valerate,
retinyl isovalerate, retinyl hexanoate, retinyl heptanoate, retinyl
octanoate, retinyl nonanoate, retinyl decanoate, retinyl
undecandate, retinyl laurate, retinyl tridecanoate, retinyl
myristate, retinyl pentadecanoate, retinyl heptadeconoate, retinyl
stearate, retinyl isostearate, retinyl nonadecanoate, retinyl
arachidonate, retinyl behenate, retinyl linoleate, retinyl oleate,
retinyl lactate, retinyl glycolate, retinyl hydroxy caprylate,
retinyl hydroxy laurate, retinyl tartarate.
[0044] The preferred ester for use in the present invention is
selected from retinyl palmitate, retinyl acetate and retinyl
propionate, because these are the most commercially available and
therefore the cheapest. Retinyl ester is also preferred due to its
efficacy.
[0045] The retinoid is employed in the inventive composition in an
amount of from about 0.001% to about 10%, preferably in an amount
of from about 0.01% to about 1%, most preferably in an amount of
from about 0.01% to about 0.5%.
[0046] Many cosmetic compositions, especially those containing
water, must be protected against the growth of potentially harmful
microorganisms. Preservatives are, therefore, necessary. Suitable
preservatives include alkyl esters of p-hydroxybenzoic acid,
hydantoin derivatives, propionate salts, and a variety of
quaternary ammonium compounds. Particularly preferred preservatives
of this invention are methyl paraben, propyl paraben,
phenoxyethanol and benzyl alcohol. Preservatives will usually be
employed in amounts ranging from about 0.1% to 2% by weight of the
composition.
[0047] The composition according to the invention is intended
primarily as a product for topical application to human skin,
especially as an agent for controlling or preventing excessive
sebum secretion.
[0048] In use, a quantity of the composition, for example from 1 to
100 ml, is applied to exposed areas of the skin, from a suitable
container or applicator and, if necessary, it is then spread over
and/or rubbed into the skin using the hand or fingers or a suitable
device.
[0049] Product Form and Packaging:
[0050] The cosmetic composition of the invention can be in any
form, e.g. formulated as a toner, gel, lotion, a fluid cream, a
soap bar or a cream. The composition can be packaged in a suitable
container to suit its viscosity and intended use by the consumer.
For example, a lotion or fluid cream can be packaged in a bottle or
a roll-ball applicator or a propellant-driven aerosol device or a
container fitted with a pump suitable for finger operation. When
the composition is a cream, it can simply be stored in a
non-deformable bottle or squeeze container, such as a tube or a
lidded jar. The invention accordingly also provides a closed
container containing a cosmetically acceptable composition as
herein defined.
[0051] The composition may also be included in capsules such as
those described in U.S. Pat. No. 5,063,057, incorporated by
reference herein.
[0052] The following specific examples further illustrate the
invention, but the invention is not limited thereto.
EXAMPLE 1
[0053] Compounds A through H were tested for their potential to
suppress sebum expression, alone or in the presence of a
retinoid.
[0054] Secondary cultures of human sebocytes obtained from an adult
male were grown in 48-well tissue culture plates (Costar Corp.;
Cambridge, Mass.) or 96-well tissue culture plates (Packard Co.;
Meriden, Conn.) until confluent. Sebocyte growth medium consisted
of Clonetics Keratinocyte Basal Medium (KBM) supplemented with 14
.mu.g/ml bovine pituitary extract, 0.4 .mu.g/ml hydrocortisone, 5
.mu.g/ml insulin, 10 ng/ml epidermal growth factor, 1.2.times.10-10
M cholera toxin, 100 units/ml penicillin, and 100 .mu.g/ml
streptomycin. All cultures were incubated at 37.degree. C. in the
presence of 7.5% CO2. Medium was changed three times per week.
[0055] On the day of experimentation, the growth medium was removed
and the sebocytes washed three times with sterile Dulbecco's
Modified Eagle Medium (DMEM; phenol red free). Fresh DMEM was added
to each sample (duplicates, triplicates, or quadruplicates
depending on the experiment) with 5 microliter of test agent
solubilized in ethanol either alone or in the presence of one or 10
micromolar of retinol. Controls consisted of addition of ethanol
alone, retinol alone, or phenol red, which has estrogen-like
activity and is included as a positive control.
[0056] Each plate was returned to the incubator for 20 hours
followed by the addition of 14C-acetate buffer (5 mM final
concentration, 56 mCi/mmol specific activity). Sebocytes were
returned to the incubator for four hours after which each culture
was rinsed three times with phosphate buffered saline to remove
unbound label. Radioactive label remaining in the sebocytes was
harvested and counted using a Beckman scintillation counter.
3TABLE 1 Compound A (n = 2) Experiment A Treatment % of Control
p-value 1 .mu.M Compound A 85.7 0.140 1 .mu.M Compound A + 1 .mu.M
Retinol 82.8 0.050 1 .mu.M Compound A + 10 .mu.M Retinol 93.2 0.187
10 .mu.M Compound A 91.3 0.496 10 .mu.M Compound A + 1 .mu.M
Retinol 85.8 0.017 10 .mu.M Compound A + 10 .mu.M Retinol 80.1
0.044 100 .mu.M Compound A 2.1 0.00005 100 .mu.M Compound A + 1
.mu.M Retinol 1.0 0.00005 100 .mu.M Compound A + 10 .mu.M Retinol
0.6 0.00004 1 .mu.M Retinol 96.5 0.397 10 .mu.M Retinol 101.8
0.636
[0057]
4TABLE 2 Compound A (n = 3) Experiment B Treatment % of Control
p-value 1 .mu.M Compound A 85.7 0.139 1 .mu.M Compound A + 1 .mu.M
Retinol 86.2 0.014 1 .mu.M Compound A + 10 .mu.M Retinol 82.8 0.186
10 .mu.M Compound A 88.8 0.246 10 .mu.M Compound A + 1 .mu.M
Retinol 45.9 0.0035 10 .mu.M Compound A + 10 .mu.M Retinol 44.3
0.0074 1 .mu.M Retinol 98.4 0.533 10 .mu.M Retinol 111.7 0.066
[0058]
5TABLE 3 Compound B (n = 3) Experiment A Treatment % of Control
p-value 1 .mu.M Compound B 94.1 0.211 1 .mu.M Compound B + 1 .mu.M
Retinol 104.1 0.596 1 .mu.M Compound B + 10 .mu.M Retinol 65.7
0.0035 10 .mu.M Compound B 89.4 0.092 10 .mu.M Compound B + 1 .mu.M
Retinol 81.8 0.231 10 .mu.M Compound B + 10 .mu.M Retinol 52.0
0.00035 28 .mu.M Phenol Red 95.3 0.530 280 .mu.M Phenol Red 15.9
8.9 .times. 10.sup.-6
[0059]
6TABLE 4 Compound B (n = 2) Experiment B Treatment % of Control
p-value 1 .mu.M Compound B 88.9 0.086 1 .mu.M Compound B + 1 .mu.M
Retinol 86.0 0.108 1 .mu.M Compound B + 10 .mu.M Retinol 74.2 0.007
10 .mu.M Compound B 82.0 0.073 10 .mu.M Compound B + 1 .mu.M
retinol 96.0 0.547 10 .mu.M Compound B + 10 .mu.M Retinol 110.9
0.038 100 .mu.M Compound B 1.7 0.00016 100 .mu.M Compound B + 1
.mu.M Retinol 0.8 0.00012 100 .mu.M Compound B + 10 .mu.M Retinol
0.6 0.00012 1 .mu.M Retinol 96.5 0.397 10 .mu.M Retinol 101.8
0.636
[0060]
7TABLE 5 Compound C (n = 4) Experiment A Treatment % of Control
p-value 1 .mu.M Compound C 66.4 0.029166 1 .mu.M Compound C + 1
.mu.M Retinol 37.8 0.000465 1 .mu.M Compound C + 10 .mu.M Retinol
48.5 0.005775 10 .mu.M Compound C 56.1 0.006919 10 .mu.M Compound C
+ 1 .mu.M Retinol 37.4 0.000573 10 .mu.M Compound C + 10 .mu.M
Retinol 47.5 0.0076 28 .mu.M Phenol Red 74.7 0.075611
[0061]
8TABLE 6 Compound C (n = 4) Experiment B Treatment % of Control
p-value 0.1 .mu.M Compound C 102.7 0.750 0.1 .mu.M Compound C + 1
.mu.M Retinol 95.1 0.308 0.1 .mu.M Compound C + 10 .mu.M Retinol
84.6 0.050 1 .mu.M Compound C 91.4 0.011 1 .mu.M Compound C + 1
.mu.M Retinol 83.7 0.015 1 .mu.M Compound C + 10 .mu.M Retinol 70.3
0.055 10 .mu.M Compound C 41.5 0.00025 10 .mu.M Compound C + 1
.mu.M Retinol 27.5 0.00056 10 .mu.M Compound C + 10 .mu.M Retinol
1.4 0.00002 1 .mu.M Retinol 99.9 0.987 10 .mu.M Retinol 100.1 0.765
28 .mu.M Phenol Red 67.6 0.0055 280 .mu.M Phenol Red 56.8
0.0057
[0062]
9TABLE 7 Compound D (n = 3) Experiment A Treatment % of Control
p-value 1 .mu.M Compound D 77.6 0.0102 1 .mu.M Compound D + 1 .mu.M
Retinol 96.9 0.565 1 .mu.M Compound D + 10 .mu.M Retinol 74.6
0.0034 10 .mu.M Compound D 82.7 0.0117 10 .mu.M Compound D + 1
.mu.M Retinol 97.1 0.568 10 .mu.M Compound D + 10 .mu.M Retinol
76.8 0.0136 280 .mu.M Phenol Red 13.2 0.0001 1 .mu.M Retinol 98.1
0.394 10 .mu.M Retinol 105.8 0.476
[0063]
10TABLE 8 Compound D (n = 2) Experiment B Treatment % of Control
p-value 1 .mu.M Compound D 80.1 0.0964 1 .mu.M Compound D + 1 .mu.M
Retinol 75.4 0.0165 1 .mu.M Compound D + 10 .mu.M Retinol 74.3
0.0699 10 .mu.M Compound D 101.2 0.908 10 .mu.M Compound D + 1
.mu.M Retinol 104.6 0.689 10 .mu.M Compound D + 10 .mu.M Retinol
88.7 0.239 100 .mu.M Compound D 1.8 0.0010 100 .mu.M Compound D + 1
.mu.M Retinol 1.1 0.0010 100 .mu.M Compound D + 10 .mu.M Retinol
0.5 0.0010 1 .mu.M Retinol 96.5 0.397 10 .mu.M Retinol 101.8
0.636
[0064]
11TABLE 9 Compound E (n = 3) Treatment % of Control p-value 1 .mu.M
Compound E 88.0 0.028 1 .mu.M Compound E + 1 .mu.M Retinol 72.1
0.055 1 .mu.M Compound E + 10 .mu.M Retinol 62.4 0.010 10 .mu.M
Compound E 92.3 0.069 10 .mu.M Compound E + 1 .mu.M Retinol 73.0
0.001 10 .mu.M Compound E + 10 .mu.M Retinol 79.5 0.036 28 .mu.M
Phenol Red 95.3 0.530 280 .mu.M Phenol Red 15.9 8.9 .times.
10.sup.-6
[0065]
12TABLE 10 Compound F (n = 4) Experiment A Treatment % of Control
p-value 1 .mu.M Compound F 72.3 0.0938 1 .mu.M Compound F + 1 .mu.M
Retinol 35.7 0.000268 1 .mu.M Compound F + 10 .mu.M Retinol 29.3
0.000264 10 .mu.M Compound F 26.7 0.000564 10 .mu.M Compound F + 1
.mu.M Retinol 15.3 0.000048 10 .mu.M Compound F + 10 .mu.M Retinol
16.7 0.00004 28 .mu.M Phenol Red 84.4 0.26672 280 .mu.M Phenol Red
16.9 0.000041
[0066]
13TABLE 11 Compound F (n = 3) Experiment B Treatment % of Control
p-value 0.1 .mu.M Compound F 95.8 0.819 0.1 .mu.M Compound F + 1
.mu.M Retinol 92.8 0.817 0.1 .mu.M Compound F + 10 .mu.M Retinol
83.6 0.077 1 .mu.M Compound F 90.2 0.383 1 .mu.M Compound F + 1
.mu.M Retinol 84.0 0.075 1 .mu.M Compound F + 10 .mu.M Retinol 71.2
0.0099 10 .mu.M Compound F 71.2 0.007 10 .mu.M Compound F + 1 .mu.M
Retinol 59.4 0.006 10 .mu.M Compound F + 10 .mu.M Retinol 27.0 4.5
.times. 10.sup.-5 28 .mu.M Phenol Red 67.6 0.0057 280 .mu.M Phenol
Red 56.8 0.0298 1 .mu.M Retinol 99.9 0.987 10 .mu.M Retinol 100.1
0.765
[0067]
14TABLE 12 Compound G (n = 3) Experiment A Treatment % of Control
p-value 1 .mu.M Compound G 77.3 0.0024 1 .mu.M Compound G + 1 .mu.M
Retinol 114.5 0.076 1 .mu.M Compound G + 10 .mu.M Retinol 80.2
0.021 10 .mu.M Compound F 75.0 0.0009 10 .mu.M Compound G + 1 .mu.M
Retinol 65.3 0.026 10 .mu.M Compound G + 10 .mu.M Retinol 63.8
0.0006 1 .mu.M Retinol 85.5 0.0001 10 .mu.M Retinol 81.8 0.0088
[0068]
15TABLE 13 Compound G (n = 4) Experiment B Treatment % of Control p
value 1 .mu.M Compound G 70.7 0.0966 1 .mu.M Compound G + 1 .mu.M
Retinol 40.4 0.0003 1 .mu.M Compound G + 10 .mu.M Retinol 39.1
0.00179 10 .mu.M Compound G 67.7 0.0644 10 .mu.M Compound G + 1
.mu.M Retinol 27.7 0.00009 10 .mu.M Compound G + 10 .mu.M Retinol
29.2 0.00066 28 .mu.M Phenol Red 84.4 0.26672 280 .mu.M Phenol Red
16.9 0.000041
[0069]
16TABLE 14 Compound G (n = 3) Experiment C Treatment % of Control p
value 1 .mu.M Compound G 105.2 0.472 1 .mu.M Compound G + 10 .mu.M
Retinol 102.9 0.666 10 .mu.M Compound G 63.0 0.00196 10 .mu.M
Compound G + 10 .mu.M Retinol 75.4 0.0373 100 .mu.M Compound G 2.0
0.000018 100 .mu.M Compound G + 10 .mu.M Retinol 0.6 0.000017 10
.mu.M Retinol 104.8 0.3559
[0070]
17TABLE 15 Compound H (n = 2) Experiment A Treatment % of Control
p-value 1 .mu.M Compound H 74.8 0.009 1 .mu.M Compound H + 1 .mu.M
Retinol 86.4 0.291 1 .mu.M Compound H + 10 .mu.M Retinol 72.8 0.003
10 .mu.M Compound H 74.6 0.005 10 .mu.M Compound H + 1 .mu.M
Retinol 76.6 0.002 10 .mu.M Compound H + 10 .mu.M Retinol 80.2
0.021 100 .mu.M Compound H 79.8 0.078 100 .mu.M Compound H + 1
.mu.M Retinol 67.6 0.002 100 .mu.M Compound H + 10 .mu.M Retinol
27.2 0.026 1 .mu.M Retinol 96.5 0.397 10 .mu.M Retinol 101.8
0.636
[0071]
18TABLE 16 Compound H (n = 6) Experiment B Treatment % of Control
p-value 1 .mu.M Compound H 65.9 0.010 1 .mu.M Compound H + 1 .mu.M
Retinol 76.8 0.137 1 .mu.M Compound H + 10 .mu.M Retinol 68.0 0.017
10 .mu.M Compound H 71.1 0.0144 10 .mu.M Compound H + 1 .mu.M
Retinol 71.0 0.0262 10 .mu.M Compound H + 10 .mu.M Retinol 73.5
0.0855 280 .mu.M Phenol Red 73.0 0.0235 1 .mu.M Retinol 99.3 0.953
10 .mu.M Retinol 95.2 0.750
[0072]
19TABLE 17 Compound H (n = 3) Experiment C Treatment % of Control
p-value 1 .mu.M Compound H 102.7 0.786 1 .mu.M Compound H + 10
.mu.M Retinol 99.9 0.989 10 .mu.M Compound H 111.7 0.303 10 .mu.M
Compound H + 10 .mu.M Retinol 100.4 0.940 100 .mu.M Compound H 73.6
0.0153 100 .mu.M Compound H + 10 .mu.M Retinol 44.4 0.0450 10 .mu.M
Retinol 104.8 0.3559
[0073] It can be seen from the results in Tables 1-17, that
Compounds A through H had sebum suppressive activity. Retinol alone
was inactive, but Compounds C, and E through H had improved
activity when combined with retinol.
[0074] It should be understood that the specific forms of the
invention herein illustrated and described are intended to be
representative only. Changes, including but not limited to those
suggested in this specification, may be made in the illustrated
embodiments without departing from the clear teachings of the
disclosure. Accordingly, reference should be made to the following
appended claims in determining the full scope of the invention.
* * * * *