(en)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.

1.ApplicationNumber: US-87315901-A
1.PublishNumber: US-6355687-B1
2.Date Publish: 20020312
3.Inventor: BAJOR JOHN STEVEN
POCALYKO DAVID JOSEPH

4.Inventor Harmonized: BAJOR JOHN STEVEN(US)
POCALYKO DAVID JOSEPH(US)

5.Country: US
6.Claims:
(en)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.

7.Description:
(en)This application claims benefit to provisional application No. 60,215,648, filed Jun. 30, 2000.


FIELD OF THE INVENTION
Cosmetic methods and compositions containing iminodibenzyl or fluorene derivatives.
BACKGROUND OF THE INVENTION
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
The present invention includes, in its first aspect, a cosmetic composition comprising:
(i) from about 0.001% to about 50% of a substituted iminodibenzyl compound
a substituted fluorine compound
selected from the group consisting of compounds A through H as follows:









Compound
R
Complete Structure



A





















B





















C





















D





















E





















F





















G





















H
















































and
(ii) a cosmetically acceptable vehicle.
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.
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
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.
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.
The preferred compositions are skin care compositions, in order to deliver anti-sebum benefit to the skin.
The term “skin” as used herein includes the skin on the face, neck, chest, back, arms, hands, legs and scalp.
The inventive methods and compositions include the substituted iminodibenzyl compound
a substituted fluorine compound
selected from the group consisting of compounds A through H as follows:









Compound
R
Complete Structure



A





















B





















C





















D





















E





















F





















G





















H
















































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%.
The substituted iminodibenzyl or fluorine compounds can be obtained from New Chemical Entities, Inc. (Bothell, Wash.).
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.
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.
Besides water, relatively volatile solvents may also serve as carriers within compositions of the present invention. Most preferred are monohydric C 1 -C 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.
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.
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° 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° 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° C.
Among the ester emollients are:
(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.
(2) Ether-esters such as fatty acid esters of ethoxylated fatty alcohols.
(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.
(4) Wax esters such as beeswax, spermaceti, myristyl myristate, stearyl stearate and arachidyl behenate.
(5) Sterols esters, of which cholesterol fatty acid esters are examples thereof.
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.
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.
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.
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.
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.
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 10 -C 20 fatty alcohol or acid hydrophobe condensed with from 2 to 100 moles of ethylene oxide or propylene oxide per mole of hydrophobe; C 2 -C 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 8 -C 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.
Preferred anionic surfactants include soap, alkyl ether sulfate and sulfonates, alkyl sulfates and sulfonates, alkylbenzene sulfonates, alkyl and dialkyl sulfosuccinates, C 8 -C 20 acyl isethionates, acyl glutamates, C 8 -C 20 alkyl ether phosphates and combinations thereof.
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.
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®) 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.
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.
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.
Retinyl ester is an ester of retinol. The term “retinol” has been defined above. Retinyl esters suitable for use in the present invention are C1-C30 esters of retinol, preferably C2-C20 esters, and most preferably C2, C3, and C16 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.
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.
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%.
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.
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.
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.
Product Form and Packaging
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.
The composition may also be included in capsules such as those described in U.S. Pat. No. 5,063,057, incorporated by reference herein.


The following specific examples further illustrate the invention, but the invention is not limited thereto.
EXAMPLE 1
Compounds A through H were tested for their potential to suppress sebum expression, alone or in the presence of a retinoid.
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 μg/ml bovine pituitary extract, 0.4 μg/ml hydrocortisone, 5 μg/ml insulin, 10 ng/ml epidermal growth factor, 1.2×10−10 M cholera toxin, 100 units/ml penicillin, and 100 μg/ml streptomycin. All cultures were incubated at 37° C. in the presence of 7.5% CO2. Medium was changed three times per week.
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.
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.





TABLE 1



Compound A (n = 2)

Experiment A





Treatment
% of Control
p-value







1 μM Compound A
85.7
0.140

1 μM Compound A + 1 μM Retinol
82.8
0.050

1 μM Compound A + 10 μM Retinol
93.2
0.187

10 μM Compound A
91.3
0.496

10 μM Compound A + 1 μM Retinol
85.8
0.017

10 μM Compound A + 10 μM Retinol
80.1
0.044

100 μM Compound A
2.1
0.00005

100 μM Compound A + 1 μM Retinol
1.0
0.00005

100 μM Compound A + 10 μM Retinol
0.6
0.00004

1 μM Retinol
96.5
0.397

10 μM Retinol
101.8
0.636








































TABLE 2



Compound A (n = 3)

Experiment B





Treatment
% of Control
p-value







1 μM Compound A
85.7
0.139

1 μM Compound A + 1 μM Retinol
86.2
0.014

1 μM Compound A + 10 μM Retinol
82.8
0.186

10 μM Compound A
88.8
0.246

10 μM Compound A + 1 μM Retinol
45.9
0.0035

10 μM Compound A + 10 μM Retinol
44.3
0.0074

1 μM Retinol
98.4
0.533

10 μM Retinol
111.7
0.066





































TABLE 3



Compound B (n = 3)

Experiment A





Treatment
% of Control
p-value







1 μM Compound B
94.1
0.211

1 μM Compound B + 1 μM Retinol
104.1
0.596

1 μM Compound B + 10 μM Retinol
65.7
0.0035

10 μM Compound B
89.4
0.092

10 μM Compound B + 1 μM Retinol
81.8
0.231

10 μM Compound B + 10 μM Retinol
52.0
0.00035

28 μM Phenol Red
95.3
0.530

280 μM Phenol Red
15.9
8.9 × 10 −6





































TABLE 4



Compound B (n = 2)

Experiment B





Treatment
% of Control
p-value







1 μM Compound B
88.9
0.086

1 μM Compound B + 1 μM Retinol
86.0
0.108

1 μM Compound B + 10 μM Retinol
74.2
0.007

10 μM Compound B
82.0
0.073

10 μM Compound B + 1 μM retinol
96.0
0.547

10 μM Compound B + 10 μM Retinol
110.9
0.038

100 μM Compound B
1.7
0.00016

100 μM Compound B + 1 μM Retinol
0.8
0.00012

100 μM Compound B + 10 μM Retinol
0.6
0.00012

1 μM Retinol
96.5
0.397

10 μM Retinol
101.8
0.636








































TABLE 5



Compound C (n = 4)

Experiment A





Treatment
% of Control
p-value







1 μM Compound C
66.4
0.029166

1 μM Compound C + 1 μM Retinol
37.8
0.000465

1 μM Compound C + 10 μM Retinol
48.5
0.005775

10 μM Compound C
56.1
0.006919

10 μM Compound C + 1 μM Retinol
37.4
0.000573

10 μM Compound C + 10 μM Retinol
47.5
0.0076

28 μM Phenol Red
74.7
0.075611




































TABLE 6



Compound C (n = 4)

Experiment B





Treatment
% of Control
p-value







0.1 μM Compound C
102.7
0.750

0.1 μM Compound C + 1 μM Retinol
95.1
0.308

0.1 μM Compound C + 10 μM Retinol
84.6
0.050

1 μM Compound C
91.4
0.011

1 μM Compound C + 1 μM Retinol
83.7
0.015

1 μM Compound C + 10 μM Retinol
70.3
0.055

10 μM Compound C
41.5
0.00025

10 μM Compound C + 1 μM Retinol
27.5
0.00056

10 μM Compound C + 10 μM Retinol
1.4
0.00002

1 μM Retinol
99.9
0.987

10 μM Retinol
100.1
0.765

28 μM Phenol Red
67.6
0.0055

280 μM Phenol Red
56.8
0.0057










































TABLE 7



Compound D (n = 3)

Experiment A





Treatment
% of Control
p-value







1 μM Compound D
77.6
0.0102

1 μM Compound D + 1 μM Retinol
96.9
0.565

1 μM Compound D + 10 μM Retinol
74.6
0.0034

10 μM Compound D
82.7
0.0117

10 μM Compound D + 1 μM Retinol
97.1
0.568

10 μM Compound D + 10 μM Retinol
76.8
0.0136

280 μM Phenol Red
13.2
0.0001

1 μM Retinol
98.1
0.394

10 μM Retinol
105.8
0.476






































TABLE 8



Compound D (n = 2)

Experiment B





Treatment
% of Control
p-value







1 μM Compound D
80.1
0.0964

1 μM Compound D + 1 μM Retinol
75.4
0.0165

1 μM Compound D + 10 μM Retinol
74.3
0.0699

10 μM Compound D
101.2
0.908

10 μM Compound D + 1 μM Retinol
104.6
0.689

10 μM Compound D + 10 μM Retinol
88.7
0.239

100 μM Compound D
1.8
0.0010

100 μM Compound D + 1 μM Retinol
1.1
0.0010

100 μM Compound D + 10 μM Retinol
0.5
0.0010

1 μM Retinol
96.5
0.397

10 μM Retinol
101.8
0.636








































TABLE 9



Compound E (n = 3)





Treatment
% of Control
p-value







1 μM Compound E
88.0
0.028

1 μM Compound E + 1 μM Retinol
72.1
0.055

1 μM Compound E + 10 μM Retinol
62.4
0.010

10 μM Compound E
92.3
0.069

10 μM Compound E + 1 μM Retinol
73.0
0.001

10 μM Compound E + 10 μM Retinol
79.5
0.036

28 μM Phenol Red
95.3
0.530

280 μM Phenol Red
15.9
8.9 × 10 −6




































TABLE 10



Compound F (n = 4)

Experiment A





Treatment
% of Control
p-value







1 μM Compound F
72.3
0.0938

1 μM Compound F + 1 μM Retinol
35.7
0.000268

1 μM Compound F + 10 μM Retinol
29.3
0.000264

10 μM Compound F
26.7
0.000564

10 μM Compound F + 1 μM Retinol
15.3
0.000048

10 μM Compound F + 10 μM Retinol
16.7
0.00004

28 μM Phenol Red
84.4
0.26672

280 μM Phenol Red
16.9
0.000041





































TABLE 11



Compound F (n = 3)

Experiment B





Treatment
% of Control
p-value







0.1 μM Compound F
95.8
0.819

0.1 μM Compound F + 1 μM Retinol
92.8
0.817

0.1 μM Compound F + 10 μM Retinol
83.6
0.077

1 μM Compound F
90.2
0.383

1 μM Compound F + 1 μM Retinol
84.0
0.075

1 μM Compound F + 10 μM Retinol
71.2
0.0099

10 μM Compound F
71.2
0.007

10 μM Compound F + 1 μM Retinol
59.4
0.006

10 μM Compound F + 10 μM Retinol
27.0
4.5 × 10 −5

28 μM Phenol Red
67.6
0.0057

280 μM Phenol Red
56.8
0.0298

1 μM Retinol
99.9
0.987

10 μM Retinol
100.1
0.765










































TABLE 12



Compound G (n = 3)

Experiment A





Treatment
% of Control
p-value







1 μM Compound G
77.3
0.0024

1 μM Compound G + 1 μM Retinol
114.5
0.076

1 μM Compound G + 10 μM Retinol
80.2
0.021

10 μM Compound F
75.0
0.0009

10 μM Compound G + 1 μM Retinol
65.3
0.026

10 μM Compound G + 10 μM Retinol
63.8
0.0006

1 μM Retinol
85.5
0.0001

10 μM Retinol
81.8
0.0088





































TABLE 13



Compound G (n = 4)

Experiment B





Treatment
% of Control
p value







1 μM Compound G
70.7
0.0966

1 μM Compound G + 1 μM Retinol
40.4
0.0003

1 μM Compound G + 10 μM Retinol
39.1
0.00179

10 μM Compound G
67.7
0.0644

10 μM Compound G + 1 μM Retinol
27.7
0.00009

10 μM Compound G + 10 μM Retinol
29.2
0.00066

28 μM Phenol Red
84.4
0.26672

280 μM Phenol Red
16.9
0.000041





































TABLE 14



Compound G (n = 3)

Experiment C





Treatment
% of Control
p value







1 μM Compound G
105.2
0.472

1 μM Compound G + 10 μM Retinol
102.9
0.666

10 μM Compound G
63.0
0.00196

10 μM Compound G + 10 μM Retinol
75.4
0.0373

100 μM Compound G
2.0
0.000018

100 μM Compound G + 10 μM Retinol
0.6
0.000017

10 μM Retinol
104.8
0.3559




































TABLE 15



Compound H (n = 2)

Experiment A





Treatment
% of Control
p-value







1 μM Compound H
74.8
0.009

1 μM Compound H + 1 μM Retinol
86.4
0.291

1 μM Compound H + 10 μM Retinol
72.8
0.003

10 μM Compound H
74.6
0.005

10 μM Compound H + 1 μM Retinol
76.6
0.002

10 μM Compound H + 10 μM Retinol
80.2
0.021

100 μM Compound H
79.8
0.078

100 μM Compound H + 1 μM Retinol
67.6
0.002

100 μM Compound H + 10 μM Retinol
27.2
0.026

1 μM Retinol
96.5
0.397

10 μM Retinol
101.8
0.636








































TABLE 16



Compound H (n = 6)

Experiment B





Treatment
% of Control
p-value







1 μM Compound H
65.9
0.010

1 μM Compound H + 1 μM Retinol
76.8
0.137

1 μM Compound H + 10 μM Retinol
68.0
0.017

10 μM Compound H
71.1
0.0144

10 μM Compound H + 1 μM Retinol
71.0
0.0262

10 μM Compound H + 10 μM Retinol
73.5
0.0855

280 μM Phenol Red
73.0
0.0235

1 μM Retinol
99.3
0.953

10 μM Retinol
95.2
0.750






































TABLE 17



Compound H (n = 3)

Experiment C





Treatment
% of Control
p-value







1 μM Compound H
102.7
0.786

1 μM Compound H + 10 μM Retinol
99.9
0.989

10 μM Compound H
111.7
0.303

10 μM Compound H + 10 μM Retinol
100.4
0.940

100 μM Compound H
73.6
0.0153

100 μM Compound H + 10 μM Retinol
44.4
0.0450

10 μM Retinol
104.8
0.3559































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.
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.