U.S. patent application number 12/105957 was filed with the patent office on 2009-08-06 for methods of treating skin with aromatic skin-active ingredients.
This patent application is currently assigned to MARY KAY INC.. Invention is credited to Tiffany C. Florence, Cristi Gomez, Michelle D. Hines, Bob Walke.
Application Number | 20090197939 12/105957 |
Document ID | / |
Family ID | 40932318 |
Filed Date | 2009-08-06 |
United States Patent
Application |
20090197939 |
Kind Code |
A1 |
Walke; Bob ; et al. |
August 6, 2009 |
METHODS OF TREATING SKIN WITH AROMATIC SKIN-ACTIVE INGREDIENTS
Abstract
A method for treating skin, reducing oxidative damage to a skin
cell, reducing lipoxygenase (LO) activity in a skin cell, reducing
cyclooxygenase (COX) activity in a skin cell, reducing tumor
necrosis factor alpha (TNF-.alpha.) in a skin cell, or reduction
matrix metalloproteinase enzyme activity in a skin cell comprising
contacting skin or a skin cell with an aromatic skin-active
ingredient.
Inventors: |
Walke; Bob; (Flower Mound,
TX) ; Gomez; Cristi; (Rowlett, TX) ; Florence;
Tiffany C.; (Dallas, TX) ; Hines; Michelle D.;
(Hickory Creek, TX) |
Correspondence
Address: |
FULBRIGHT & JAWORSKI L.L.P.
600 CONGRESS AVE., SUITE 2400
AUSTIN
TX
78701
US
|
Assignee: |
MARY KAY INC.
Dallas
TX
|
Family ID: |
40932318 |
Appl. No.: |
12/105957 |
Filed: |
April 18, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61025631 |
Feb 1, 2008 |
|
|
|
Current U.S.
Class: |
514/450 ;
435/375; 514/460; 514/464; 514/473; 514/546; 514/676; 514/690;
514/703; 514/739 |
Current CPC
Class: |
A61K 8/4973 20130101;
A61K 31/365 20130101; A61K 8/37 20130101; A61K 31/35 20130101; A61K
8/498 20130101; A61K 8/34 20130101; A61K 2800/522 20130101; A61K
8/35 20130101; A61K 8/342 20130101; A61P 17/00 20180101; A61Q 19/00
20130101; A61K 31/045 20130101; A61K 8/33 20130101; A61P 29/00
20180101; A61K 31/045 20130101; A61K 2300/00 20130101; A61K 31/35
20130101; A61K 2300/00 20130101; A61K 31/365 20130101; A61K 2300/00
20130101 |
Class at
Publication: |
514/450 ;
514/690; 514/739; 514/703; 514/460; 514/464; 514/473; 514/546;
514/676; 435/375 |
International
Class: |
A61K 31/357 20060101
A61K031/357; A61K 31/12 20060101 A61K031/12; A61K 31/045 20060101
A61K031/045; A61K 31/11 20060101 A61K031/11; A61K 31/351 20060101
A61K031/351; A61K 31/34 20060101 A61K031/34; A61K 31/215 20060101
A61K031/215; A61K 31/121 20060101 A61K031/121; C12N 5/00 20060101
C12N005/00; A61P 17/00 20060101 A61P017/00 |
Claims
1. A method of treating or preventing a skin condition comprising
topically applying a composition that includes an aromatic
skin-active ingredient on skin, wherein the topical application of
the composition treats or prevents the skin condition.
2. The method of claim 1, wherein a cosmeceutically effective
amount of the aromatic skin-active ingredient is applied on the
skin.
3. The method of claim 1, wherein a cosmeceutically effective
amount is from 0.005% to 2.0% by weight of the composition.
4. The method of claim 1, wherein the aromatic skin-active
ingredient is selected from the group consisting of:
1,4-dioxacycloheptadecane-5,17-dione;
(3E)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-3-en-2-one;
1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethan-1-o-
ne;
1-(2,3,8,8-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalen-2-yl)ethan-
one;
1-(2,3,8,8-tetramethyl-1,2,3,4,6,7,8,8a-octahydronaphthalen-2-yl)etha-
none; 4-methyl-3-decen-5-ol; 2,6-dimethyl-5-heptenal;
3,3-dimethyl-5(2,2,3-trimethyl-3-cyclopenten-1-yl)-4-penten-2-ol;
3-hexen-1-ol (E) an (Z); methyl
3-oxo-2-pentylcyclopentanecarboxylate;
4-ethyl-3,7-dimethylocta-1,6-dien-3-ol;
2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol;
a-methyl-1,3-benzodioxole-5-propionaldehyde;
5-heptyldihydrofuran-2(3H)-one;
3-(4-isopropylphenyl)-2-methylpropanal; 2-methyldecanal;
2,4-nonadien-1-al; 2-dodecenal (E); 2,6-nonadien-1-al (trans,
trans; trans, cis); 1-dodecanal; 4-tert-butylcyclohexyl acetate;
methyl non-2-enoate;
1-methyl-3-(4-methylpent-3-enyl)cyclohex-3-enecarbaldehyde;
3a,4,5,6,7,7a-hexahydro-4,7-methano-1h-inden-5(or 6)-yl acetate;
3-(4-ethylphenyl)-2,2-dimethylpropanal;
3-(2-ethylphenyl)-2,2-dimethylpropanal;
(Z)-4-methyl-3H-benzo[c][1,2]dioxepin-3-one; cis-2-hexenyl acetate;
(Z)-2-(but-2-enyl)-3-methylcyclopent-2-enone; methyl
2,2-dimethyl-6-methylenecyclohexanecarboxylate;
(Z)-5-(hydroxyimino)octan-3-one;
(2,4,6-)trimethyl-3-cyclohexene-1-carboxaldehyde;
(3,5,6-)trimethyl-3-cyclohexene-1-carboxaldehyde;
5-pentyldihydrofuran-2(3H)-one; cis-6-nonenal; ethyl
3-isopropylbicyclo[2.2.1]hept-5-ene-2-carboxylate; and
3,7-dimethyl-6-octen-1-yl acetate.
5. The method of claim 1, wherein the composition includes at least
two, three, four, five, six, or seven aromatic skin-active
ingredients.
6. The method of claim 1, wherein the composition is an emulsion, a
cream, a lotion, a solution, an anhydrous base, a gel, or an
ointment.
7. A method of reducing lipoxygenase activity, cyclooxygenase
activity, tumor necrosis factor-alpha activity, matrix
metalloproteinase enzyme activity, or oxidative damage in a skin
cell comprising contacting the skin cell with an aromatic
skin-active ingredient, wherein contacting the skin cell with the
aromatic ingredient reduces lipoxygenase activity, cyclooxygenase
activity, tumor necrosis factor-alpha activity, matrix
metalloproteinase enzyme activity, or oxidative damage in the skin
cell.
8. The method of claim 7, wherein the skin cell is selected from
the group consisting of human epidermal keratinocytes, human dermal
fibroblasts, and human melanocytes.
9. The method of claim 7, wherein the aromatic skin-active
ingredient is selected from the group consisting of:
1,4-dioxacycloheptadecane-5,17-dione;
(3E)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-3-en-2-one;
1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethan-1-o-
ne;
1-(2,3,8,8-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalen-2-yl)ethan-
one;
1-(2,3,8,8-tetramethyl-1,2,3,4,6,7,8,8a-octahydronaphthalen-2-yl)etha-
none; 4-methyl-3-decen-5-ol; 2,6-dimethyl-5-heptenal;
3,3-dimethyl-5(2,2,3-trimethyl-3-cyclopenten-1-yl)-4-penten-2-ol;
3-hexen-1-ol (E) an (Z); methyl
3-oxo-2-pentylcyclopentanecarboxylate;
4-ethyl-3,7-dimethylocta-1,6-dien-3-ol;
2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol;
a-methyl-1,3-benzodioxole-5-propionaldehyde;
5-heptyldihydrofuran-2(3H)-one;
3-(4-isopropylphenyl)-2-methylpropanal; 2-methyldecanal;
2,4-nonadien-1-al; 2-dodecenal (E); 2,6-nonadien-1-al (trans,
trans; trans, cis); 1-dodecanal; 4-tert-butylcyclohexyl acetate;
methyl non-2-enoate;
1-methyl-3-(4-methylpent-3-enyl)cyclohex-3-enecarbaldehyde;
3a,4,5,6,7,7a-hexahydro-4,7-methano-1h-inden-5(or 6)-yl acetate;
3-(4-ethylphenyl)-2,2-dimethylpropanal;
3-(2-ethylphenyl)-2,2-dimethylpropanal;
(Z)-4-methyl-3H-benzo[c][1,2]dioxepin-3-one; cis-2-hexenyl acetate;
(Z)-2-(but-2-enyl)-3-methylcyclopent-2-enone; methyl
2,2-dimethyl-6-methylenecyclohexanecarboxylate;
(Z)-5-(hydroxyimino)octan-3-one;
(2,4,6-)trimethyl-3-cyclohexene-1-carboxaldehyde;
(3,5,6-)trimethyl-3-cyclohexene-1-carboxaldehyde;
5-pentyldihydrofuran-2(3H)-one; cis-6-nonenal; ethyl
3-isopropylbicyclo[2.2.1]hept-5-ene-2-carboxylate; and
3,7-dimethyl-6-octen-1-yl acetate.
10. The method of claim 7, wherein the skin cell is contacted with
at least two, three, four, five, six, or seven aromatic skin-active
ingredients.
11. The method of claim 7, wherein the aromatic skin-active
ingredient is comprised in a composition.
12. The method of claim 11, wherein the composition is an emulsion,
a cream, a lotion, a solution, an anhydrous base, a gel, or an
ointment.
13-38. (canceled)
39. A topical skin-care composition comprising an effective amount
of an aromatic skin-active ingredient.
40. The topical skin-care composition of claim 39, wherein an
effective amount is 0.005% to 2.0% by weight of the
composition.
41. The topical skin-care composition of claim 39, wherein the
composition is fragrance free.
42. The topical skin-care composition of claim 41, wherein the
composition does not include another aromatic compound.
43. The topical skin-care composition of claim 39, wherein the
aromatic skin-active ingredient is selected from the group
consisting of: 1,4-dioxacycloheptadecane-5,17-dione;
(3E)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-3-en-2-one;
1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethan-1-o-
ne;
1-(2,3,8,8-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalen-2-yl)ethan-
one;
1-(2,3,8,8-tetramethyl-1,2,3,4,6,7,8,8a-octahydronaphthalen-2-yl)etha-
none; 4-methyl-3-decen-5-ol; 2,6-dimethyl-5-heptenal;
3,3-dimethyl-5(2,2,3-trimethyl-3-cyclopenten-1-yl)-4-penten-2-ol;
3-hexen-1-ol (E) and (Z); methyl
3-oxo-2-pentylcyclopentanecarboxylate;
4-ethyl-3,7-dimethylocta-1,6-dien-3-ol;
2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol;
.alpha.-methyl-1,3-benzodioxole-5-propionaldehyde;
5-heptyldihydrofuran-2(3H)-one;
3-(4-isopropylphenyl)-2-methylpropanal; 2-methyldecanal;
2,4-nonadien-1-al; 2-dodecenal (E); 2,6-nonadien-1-al (trans,
trans; trans, cis); 1-dodecanal; 4-tert-butylcyclohexyl acetate;
methyl non-2-enoate;
1-methyl-3-(4-methylpent-3-enyl)cyclohex-3-enecarbaldehyde;
3a,4,5,6,7,7a-hexahydro-4,7-methano-1h-inden-5(or 6)-yl acetate;
3-(4-ethylphenyl)-2,2-dimethylpropanal;
3-(2-ethylphenyl)-2,2-dimethylpropanal;
(Z)-4-methyl-3H-benzo[c][1,2]dioxepin-3-one; cis-2-hexenyl acetate;
(Z)-2-(but-2-enyl)-3-methylcyclopent-2-enone; methyl
2,2-dimethyl-6-methylenecyclohexanecarboxylate;
(Z)-5-(hydroxyimino)octan-3-one;
(2,4,6-)trimethyl-3-cyclohexene-1-carboxaldehyde;
(3,5,6-)trimethyl-3-cyclohexene-1-carboxaldehyde;
5-pentyldihydrofuran-2(3H)-one; cis-6-nonenal; ethyl
3-isopropylbicyclo[2.2.1]hept-5-ene-2-carboxylate; and
3,7-dimethyl-6-octen-1-yl acetate.
44. The topical skin-care composition of claim 39, wherein the
composition includes at least two, three, four, five, six, or seven
aromatic skin-active ingredients.
45. The topical skin-care composition of claim 39, wherein the
composition is an emulsion, a cream, a lotion, a solution, an
anhydrous base, a gel, or an ointment.
46. The topical skin-care composition of claim 39, wherein the
composition does not include another skin-active ingredient.
47. The topical skin-care composition of claim 46, wherein the
composition does not include another aromatic compound.
48. The topical skin-care composition of claim 47, wherein the
composition is fragrance free.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Application No. 61/025,631, filed Feb. 1, 2008, the contents of
which are incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] A. Field of the Invention
[0003] The present invention relates generally to methods of
treating skin. In particular, the present invention concerns
topical skin care compositions that include ingredients found to
have beneficial effect on skin.
[0004] B. Description of Related Art
[0005] In the cosmetic industry, certain ingredients (both
skin-active and non active ingredients) can have rather unpleasant
odors. Such ingredients include nitrogen-containing compounds,
heterocyclic compounds, and sulfur-containing compounds. The end
result is the production of cosmetic compositions that have foul
odors.
[0006] Odor neutralizing ingredients have been used to reduce or
mask malodorous cosmetic compositions. The use of aromatic chemical
compounds and blends of such compounds has been successful in this
regard. Examples of such ingredients can be found in the
International Cosmetic Ingredient Dictionary and Handbook,
10.sup.th Edition (2004).
[0007] Therefore, one of the problems associated with using
malodorous skin-active ingredients is that additional chemical
ingredients may have to be used to mask the unpleasant odors caused
by the skin-active ingredient.
SUMMARY OF THE INVENTION
[0008] The inventors have discovered new uses of aromatic chemical
compounds that have previously been thought to be useful only as
odor neutralizing agents. In this regard, the inventors have
identified certain aromatic chemical compounds that are
cosmeceutically effective in treating skin or skin cells or
preventing skin or skin cell damage while also being capable of
reducing, masking, or preventing the intensity of malodorous
smelling cosmetic compositions (e.g., aromatic skin-active
ingredients or compounds). Therefore the compositions of the
present invention can exclude or reduce the amount of odor
neutralizing compounds in instances where an aromatic skin-active
ingredient of the present invention is used. However, the inventors
contemplate the use of odor neutralizing compounds in compositions
that also include the aromatic skin-active ingredients disclosed
throughout this specification.
[0009] In one non-limiting aspect, there is disclosed a method of
treating or preventing a skin condition comprising topically
applying a composition that includes an aromatic skin-active
ingredient on skin, wherein the topical application of the
composition treats or prevents the skin condition. In certain
embodiments, a cosmeceutically effective amount of the aromatic
skin-active ingredient is applied on the skin. Non-limiting
examples of a cosmeceutically effective amount include 0.005% to
2.0% by weight of the composition (note that other ranges are
contemplated and disclosed throughout this specification). In
certain non-limiting aspects, the aromatic skin-active ingredient
can be selected from the group consisting of those identified in
Table 1 below (e.g., 1,4-dioxacycloheptadecane-5,17-dione;
(3E)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-3-en-2-one;
1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethan-1-o-
ne;
1-(2,3,8,8-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalen-2-yl)ethan-
one;
1-(2,3,8,8-tetramethyl-1,2,3,4,6,7,8,8a-octahydronaphthalen-2-yl)etha-
none; 4-methyl-3-decen-5-ol; 2,6-dimethyl-5-heptenal;
3,3-dimethyl-5(2,2,3-trimethyl-3-cyclopenten-1-yl)-4-penten-2-ol;
3-hexen-1-ol (E) and (Z); methyl
3-oxo-2-pentylcyclopentanecarboxylate;
4-ethyl-3,7-dimethylocta-1,6-dien-3-ol;
2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol;
.alpha.-methyl-1,3-benzodioxole-5-propionaldehyde;
5-heptyldihydrofuran-2(3H)-one;
3-(4-isopropylphenyl)-2-methylpropanal; 2-methyldecanal;
2,4-nonadien-1-al; 2-dodecenal (E); 2,6-nonadien-1-al (trans,
trans; trans, cis); 1-dodecanal; 4-tert-butylcyclohexyl acetate;
methyl non-2-enoate;
1-methyl-3-(4-methylpent-3-enyl)cyclohex-3-enecarbaldehyde;
3a,4,5,6,7,7a-hexahydro-4,7-methano-1h-inden-5(or 6)-yl acetate;
3-(4-ethylphenyl)-2,2-dimethylpropanal;
3-(2-ethylphenyl)-2,2-dimethylpropanal;
(Z)-4-methyl-3H-benzo[c][1,2]dioxepin-3-one; cis-2-hexenyl acetate;
(Z)-2-(but-2-enyl)-3-methylcyclopent-2-enone; methyl
2,2-dimethyl-6-methylenecyclohexanecarboxylate;
(Z)-5-(hydroxyimino)octan-3-one;
(2,4,6-)trimethyl-3-cyclohexene-1-carboxaldehyde;
(3,5,6-)trimethyl-3-cyclohexene-1-carboxaldehyde;
5-pentyldihydrofuran-2(3H)-one; cis-6-nonenal; ethyl
3-isopropylbicyclo[2.2.1]hept-5-ene-2-carboxylate; and
3,7-dimethyl-6-octen-1-yl acetate). The composition can include a
single aromatic skin-active ingredient or any combination of
aromatic skin active ingredients. By way of example, the
composition can include at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,
12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,
29, or 30 of the aromatic skin-active ingredients, including any
combination thereof. Non-limiting examples of skin conditions
include pruritus, spider veins, lentigo, age spots, senile purpura,
keratosis, melasma, blotches, fine lines or wrinkles, nodules, sun
damaged skin, dermatitis (including, but not limited to seborrheic
dermatitis, nummular dermatitis, contact dermatitis, atopic
dermatitis, exfoliative dermatitis, perioral dermatitis, and stasis
dermatitis), psoriasis, folliculitis, rosacea, acne, impetigo,
erysipelas, erythrasma, eczema, and other inflammatory skin
conditions. In certain non-limiting aspects, the skin condition can
be caused by exposure to UV light, age, irradiation, chronic sun
exposure, environmental pollutants, air pollution, wind, cold,
heat, chemicals, disease pathologies, smoking, or lack of
nutrition. The skin can be facial skin or non-facial skin (e.g.,
arms, legs, hands, chest, back, feet, etc.). The method can further
comprise identifying a person in need of skin treatment. The person
can be a male or female. The age of the person can be at least 1,
2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60,
65, 70, 75, 80, 85, 90, 95, or more years old, or any range
derivable therein. In another aspect, the method can include
topically applying an amount effective to: increase the stratum
corneum turnover rate of the skin; increase collagen synthesis in
fibroblasts; increase cellular anti-oxidant defense mechanisms
(e.g., exogenous additions of anti-oxidants can bolster, replenish,
or prevent the loss of cellular antioxidants such as catalase and
glutathione in skin cells (e.g., keratinocytes, melanocytes,
langerhans cells, etc.); inhibit melanin production in melanocytes;
reduce or prevent oxidative damage to skin (including reducing the
amount lipid peroxides and/or protein oxidation in the skin).
[0010] In another aspect, there is disclosed a method of reducing
or preventing lipoxygenase, cyclooxygenase (COX), tumor necrosis
factor-alpha (TNF-.alpha.), or matrix metalloproteinase (MMP)
enzyme activity in a cell comprising contacting the cell with an
aromatic skin-active ingredient, wherein contacting the cell with
the aromatic ingredient reduces or prevents lipoxygenase,
cyclooxygenase (COX), tumor necrosis factor-alpha (TNF-.alpha.), or
matrix metalloproteinase (MMP) enzyme activity in the cell. Also
disclosed is a method of reducing or preventing oxidative damage in
a cell comprising contacting the cell with an aromatic skin-active
ingredient, wherein contacting the cell with the aromatic
ingredient reduces oxidative damage in the cell. The cell can be a
skin cell. Non-limiting examples of skin cells include human
epidermal keratinocytes, human dermal fibroblasts, or human
melanocytes. Non-limiting examples of cyclooxygenase include
cyclooxygenase-1 or cyclooxygenase-2. Non-limiting examples of
matrix metalloproteinase enzyme include MMP3 or MMP9. The aromatic
skin-active ingredient can be selected from the group consisting of
those identified in Table I below. The aromatic skin-active
ingredient is comprised in a composition. The cells can be
contacted with a single aromatic skin-active ingredient or any
combination of aromatic skin active ingredients. By way of example,
the cells can be contacted with at least 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,
27, 28, 29, or 30 of the aromatic skin-active ingredients,
including any combination thereof.
[0011] In certain embodiments, compositions of the present
invention can decrease the amount of internal oxidation and/or
external oxidative damage in a cell. In other aspects, the
compositions can increase collagen synthesis in a cell. The
compositions can also reduce skin inflammation, such as by reducing
inflammatory cytokine production in a cell. Non-limiting examples
of such cells include human epidermal keratinocyte, human
fibroblast dermal cell, human melanocytes, three dimensional human
cell-derived in vitro tissue equivalents comprising human
keratinocytes, human fibroblasts, or human melanocytes, or any
combination thereof (e.g., combination of human keratinocytes and
human fibroblasts or a combination of human keratinocytes and human
melanocytes).
[0012] Also disclosed is a method of lightening skin or evening
skin tone comprising applying the compositions of the present
invention to the skin. The method can further comprise identify a
person in need of lightening skin or evening skin tone. The methods
can further include inhibiting melanogenesis in a skin cell,
inhibiting tyrosinase or tyrosinase synthesis in a skin cell, or
inhibiting melanin transport to keratinocytes in a skin cell. The
composition can act as an alpha melanin stimulatory hormone
antagonist. The composition can even out pigmentation of the skin.
In non-limiting aspect, lightening skin can include reducing the
appearance of an age spot, a skin discoloration, or a freckle.
[0013] Also disclosed is a method of treating hyperpigmentation
comprising applying the compositions of the present invention to
the skin. The method can also comprise identifying a person in need
of treating hyperpigmentation. Additional methods contemplated by
the inventor include methods for reducing the appearance of an age
spot, a skin discoloration, or a freckle, reducing or preventing
the appearance of fine lines or wrinkles in skin, or increasing the
firmness of skin.
[0014] Another aspect of the present invention includes a
composition comprising an effective amount of an aromatic
skin-active ingredient or combination of such ingredients. The
composition can be a topical skin-care composition. The aromatic
skin-active ingredient can be selected from the group consisting
of: those identified in Table 1 below. The composition can be
fragrance free. In certain aspects, the composition does not
include another aromatic compound. The composition does not include
another skin-active ingredient in certain embodiments and/or does
not include another aromatic compound. The composition can include
a single aromatic skin-active ingredient or any combination of
aromatic skin active ingredients. By way of example, the
composition can include at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,
12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,
29, or 30 of the aromatic skin-active ingredients, including any
combination thereof. The combination of the aromatic skin-active
ingredients can work together synergistically or in a complementary
fashion to produce effects that exceed the effects of what would be
expected if the extracts were used in separate compositions.
Non-limiting synergistic effects include the reduction of internal
or external oxidative damage, increased collagen production,
reduction in inflammatory responses and the inhibition of
melanogenesis, or reduce or prevent lipoxygenase, cyclooxygenase
(COX), tumor necrosis factor-alpha (TNF-.alpha.), or matrix
metalloproteinase (MMP) enzyme activity in a skin cell. In certain
embodiments, the compositions are formulated into topical skin care
compositions. The compositions can be cosmetic compositions. In
other aspects, the compositions can be formulated as emulsions
(e.g., oil-in-water and water-in-oil emulsions), creams, lotions,
solutions (e.g., aqueous or hydro-alcoholic solutions), anhydrous
bases (e.g., lipstick or a powder), gels, and ointments. In other
non-limiting embodiments, the compositions of the present invention
can be included in anti-aging, cleansing, or moisturizing products.
The compositions can also be formulated for topical skin
application at least 1, 2, 3, 4, 5, 6, 7, or more times a day
during use. In other aspects of the present invention, compositions
can be storage stable or color stable, or both. It is also
contemplated that the viscosity of the composition can be selected
to achieve a desired result (e.g., depending on the type of
composition desired, the viscosity of such composition can be from
about 1 cps to well over 1 million cps or any range or integer
derivable therein (e.g., 2 cps, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30,
40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800,
900, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10000,
20000, 30000, 40000, 50000, 60000, 70000, 80000, 90000, 100000,
200000, 300000, 400000, 500000, 600000, 700000, 800000, 900000,
1000000 cps, etc. as measured on a Brookfield Viscometer using a TC
spindle at 2.5 rpm at 25.degree. C.). The compositions of the
present invention can also be modified to have a desired oxygen
radical absorbance capacity (ORAC) value. In certain non-limiting
aspects, the compositions of the present invention can be modified
to have an ORAC value per mg of at least about 1, 2, 3, 4, 5, 6, 7,
8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24,
25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 95,
100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 2000, 3000,
4000, 5000, 6000, 7000, 8000, 9000, 10000, 15000, 20000, 30000,
50000, 100000 or more or any range derivable therein. The
compositions in non-limiting aspects can have a pH of about 6 to
about 9. In other aspects, the pH can be 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, 13, or 14. In other aspects, the compositions can be
sunscreens having a sun protection factor (SPF) of 1, 5, 10, 15,
20, 25, 30, 35, 40, 45, 50, 55, or more. In certain aspects, the
compositions include odor neutralizing ingredients other than the
aromatic skin-active ingredients disclosed throughout this
specification.
[0015] Also contemplated are kits that includes the compositions of
the present invention. In certain embodiments, the composition is
comprised in a container. The container can be a bottle, dispenser,
or package. The container can dispense a pre-determined amount of
the composition. In certain aspects, the compositions is dispensed
in a spray, dollop, or liquid. The container can include indicia on
its surface. The indicia can be a word, an abbreviation, a picture,
or a symbol.
[0016] Also contemplated is a product comprising a composition of
the present invention. In non-limiting aspects, the product can be
a cosmetic product. The cosmetic product can be those described in
other sections of this specification or those known to a person of
skill in the art. Non-limiting examples of products include a
moisturizer, a cream, a lotion, a skin softener, a foundation, a
night cream, a lipstick, a cleanser, a toner, a sunscreen, a mask,
or an anti-aging product.
[0017] It is contemplated that any embodiment discussed in this
specification can be implemented with respect to any method or
composition of the invention, and vice versa. Furthermore,
compositions of the invention can be used to achieve methods of the
invention.
[0018] The term "about" or "approximately" are defined as being
close to as understood by one of ordinary skill in the art, and in
one non-limiting embodiment the terms are defined to be within 10%,
preferably within 5%, more preferably within 1%, and most
preferably within 0.5%.
[0019] The terms "inhibiting" or "reducing" or any variation of
these terms, when used in the claims and/or the specification
includes any measurable decrease or complete inhibition to achieve
a desired result.
[0020] The term "effective," as that term is used in the
specification and/or claims, means adequate to accomplish a
desired, expected, or intended result. For instance, an "effective
amount" or a "cosmeceutically effective amount" or a
"therapeutically effective amount" means an amount that is adequate
to accomplish a desired, expected, or intended result. Use of an
aromatic skin-active ingredient(s) in the methods and compositions
of the present invention can include an "effective amount" or a
"cosmeceutically effective amount" or a "therapeutically effective
amount." Such amounts can vary depending on the aromatic
skin-active ingredient(s), the condition to be treated or prevented
and its severity, the manner of administration, and the age of the
person to be treated, but can be determined routinely by one of
ordinary skill in the art having regard to his own knowledge and to
this disclosure.
[0021] The use of the word "a" or "an" when used in conjunction
with the term "comprising" in the claims and/or the specification
may mean "one," but it is also consistent with the meaning of "one
or more," "at least one," and "one or more than one."
[0022] The use of the term "or" in the claims is used to mean
"and/or" unless explicitly indicated to refer to alternatives only
or the alternatives are mutually exclusive, although the disclosure
supports a definition that refers to only alternatives and
"and/or."
[0023] As used in this specification and claim(s), the words
"comprising" (and any form of comprising, such as "comprise" and
"comprises"), "having" (and any form of having, such as "have" and
"has"), "including" (and any form of including, such as "includes"
and "include") or "containing" (and any form of containing, such as
"contains" and "contain") are inclusive or open-ended and do not
exclude additional, unrecited elements or method steps.
[0024] Other objects, features and advantages of the present
invention will become apparent from the following detailed
description. It should be understood, however, that the detailed
description and the examples, while indicating specific embodiments
of the invention, are given by way of illustration only.
Additionally, it is contemplated that changes and modifications
within the spirit and scope of the invention will become apparent
to those skilled in the art from this detailed description.
DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
[0025] In today's image conscious society, people are continually
looking for a product that can improve the visual appearance of
their skin. Often times, aged skin, uneven skin tone, or skin
damaged by environmental factors such as UV light, chronic sun
exposure, environmental pollutants, chemicals, disease pathologies,
or smoking, is associated with unattractive skin. Previous attempts
to improve the visual appearance of skin often involved the use of
skin-active ingredients that have an unpleasant or malodorous
smell.
[0026] The inventors have discovered new uses of aromatic chemical
compounds that have previously been thought to be useful only as
odor neutralizing agents. As explained in non-limiting aspects in
the following sections, the aromatic skin-active ingredients
discovered by the inventors have been shown to be effective at
treating a wide range of skin ailments and preventing skin damage.
These compounds can be incorporated into all types of cosmetic
compositions. These and other aspect of the present invention are
described in further non-limiting detail below.
A. AROMATIC SKIN-ACTIVE INGREDIENTS
[0027] The inventor has discovered that the compounds listed in
Table 1 have surprising and unexpected properties that are
beneficial to human skin. Data supporting these properties
(including how these data were obtained) are presented in the
EXAMPLES section below which is incorporated into this section by
reference. The beneficial properties of these compounds range from
reducing or preventing oxidative damage to skin or skin cells,
reducing or preventing lipoxygenase activity in skin or skin cells,
reducing or inhibiting cyclooxygenase (COX) activity in skin or
skin cells, reducing or inhibiting tumor necrosis factor alpha
(TNF-.alpha.) in skin or skin cells, and reducing or inhibiting
matrix metalloproteinase (MMP) enzyme activity in skin or skin
cells.
TABLE-US-00001 TABLE 1 (Aromatic Skin-Active Ingredients) Chemical
Name Structure CAS # (alternate name) ##STR00001## 105-95-3
1,4-dioxacycloheptadecane- 5,17-dione (Ethylene Brassylate)
##STR00002## 14901-07-6 (3E)-4-(2,6,6- trimethylcyclohex-1-en-1-
yl)but-3-en-2-one (Beta Ionone) ##STR00003## 54464-57-2, 68155-66-8
and 68155-67-9 1-(1,2,3,4,5,6,7,8-octahydro- 2,3,8,8-tetramethyl-2-
naphthalenyl)ethan-1-one; 1-(2,3,8,8-tetramethyl- 1,2,3,5,6,7,8,8a-
octahydronaphthalen-2- yl)ethanone; and 1-(2,3,8,8-
tetramethyl-1,2,3,4,6,7,8,8a- octahydronaphthalen-2- yl)ethanone
(Iso E super) ##STR00004## 81782-77-6 4-methyl-3-decen-5-ol
##STR00005## 106-72-9 2,6-dimethyl-5-heptenal (Melanol)
##STR00006## 107898-54-4 3,3-dimethyl-5(2,2,3-
trimethyl-3-cyclopenten-1- yl)-4-penten-2-ol (Polysantol)
##STR00007## 928-96-1 3-hexen-1-ol (E) and (Z) ##STR00008##
24851-98-7 methyl 3-oxo-2- pentylcyclopentanecarboxylate (Methyl
Dihydro Jasmonate) ##STR00009## 10339-55-6
4-ethyl-3,7-dimethylocta- 1,6-dien-3-ol (Ethyl Linalool)
##STR00010## 63500-71-0 2-isobutyl-4- methyltetrahydro-2H-pyran-
4-ol (Florol) ##STR00011## 1205-17-0
.alpha.-methyl-1,3-benzodioxole- 5-propionaldehyde (Helional)
##STR00012## 104-67-6 5-heptyldihydrofuran- 2(3H)-one (Aldehyde
C-14) ##STR00013## 103-95-7 3-(4-isopropylphenyl)-2- methylpropanal
(Cyclamen Aldehyde) ##STR00014## 19009-56-4 2-methyldecanal
(Aldehyde C-11 MOA) ##STR00015## 5910-87-2 2,4-nonadien-1-al
##STR00016## 20407-84-5 2-dodecenal (E) (trans-2-dodecenal)
##STR00017## 112-54-9 1-dodecanal (Aldehyde C-12 Lauric)
##STR00018## 557-48-2 and 17587-33-6 2,6-nonadien-1-al (trans,
trans; trans, cis) ##STR00019## 32210-23-4 4-tert-butylcyclohexyl
acetate (Vertenex .RTM. H.C.) ##STR00020## 111-79-5 methyl
non-2-enoate (Neofolione) ##STR00021## 52474-60-9
1-methyl-3-(4-methylpent- 3-enyl)cyclohex-3- enecarbaldehyde
(Precyclemone B) ##STR00022## 54830-99-8 3a,4,5,6,7,7a-hexahydro-
4,7-methano-1h-inden-5(or 6)-yl acetate (Cyclacet) ##STR00023##
67634-15-5 and 67634-14-4 3-(4-ethylphenyl)-2,2- dimethylpropanal
and 3-(2-ethylphenyl)-2,2- dimethylpropanal (Floralozone)
##STR00024## 28940-11-6 (Z)-4-methyl-3H-
benzo[c][1,2]dioxepin-3-one (Calone 1951) ##STR00025## 3681-71-8
cis-2-hexenyl acetate (Leaf Acetate) ##STR00026## 1128-08-1
(Z)-2-(but-2-enyl)-3- methylcyclopent-2-enone (Dihydro-jasmone)
##STR00027## 81752-87-6 methyl 2,2-dimethyl-6-
methylenecyclohexanecarboxylate (Romascone .RTM.) ##STR00028##
22457-23-4 (Z)-5-(hydroxyimino)octan- 3-one (Stemone) ##STR00029##
1335-66-6 and 67634-07-5 (2,4,6-)trimethyl-3- cyclohexene-1-
carboxaldehyde and (3,5,6-) trimethyl-3-cyclohexene-1-
carboxaldehyde (Iso Cyclo Citral) ##STR00030## 104-61-0
5-pentyldihydrofuran- 2(3H)-one (Aldehyde C-18) ##STR00031##
2277-19-2 cis-6-nonenal ##STR00032## 116126-82-0 ethyl 3-
isopropylbicyclo[2.2.1]hept- 5-ene-2-carboxylate (Herbanante)
##STR00033## 150-84-5 3,7-dimethyl-6-octen-1-yl acetate
(citronellyl acetate)
[0028] The aromatic skin-active compounds and derivatives and
modifications of the same can be prepared by using convention
chemical synthesis techniques (see, e.g., Organic Chemistry,
5.sup.th Ed., which is incorporated by reference).
[0029] 1. Oxidative Damage in Skin Cells
[0030] Free radicals are chemically active molecular fragments that
have a charge due to excess or a deficient number of electrons.
Reactive oxygen species (ROS), free radicals containing oxygen,
generate oxidative damage to human skin cells through endogenous
(cellular) and exogenous (environmental) mechanisms. In aged skin,
oxidative damage accumulates which results in lost skin elasticity
and increased fine lines and wrinkles. Antioxidants block the
oxidation process by neutralizing, or reduce, this energy to
protect cellular functions and prevent damage to cell proteins.
Thus, reductions in oxidative damage in skin can reduce the signs
of signs of premature aging.
[0031] 2. Lipoxygenase
[0032] Lipoxygenase enzymes catalyze the oxidative conversion of
arachadonic acid to hydroxyeicosotrienenoic (HETE), that are
subsequently converted to leukotrienes. Increased levels of
arachadonic acid is associated with sustained inflammation in human
skin. Thus, compounds which reduce the activity of lipoxygenase
enzymes can act as a potent mediator of skin inflammation.
[0033] 3. Cyclooxygenase (COX)
[0034] COX is a bifunctional enzyme exhibiting both cyclooxygenase
and peroxidase activities. The cyclooxygenase activity converts
arachadonic acid to a hydroperoxy endoperoxide (Prostaglandin G2;
PGG2) and the peroxidase component reduces the endoperoxide
(Prostaglandin H2; PGH2) to the precursor of prostaglandins,
thromboxanes, and prostacyclins, key mediators of skin
inflammation. Thus, compounds which reduce the enzymatic activity
of COX will also mediate the inflammatory response in skin.
[0035] 4. Tumor Necrosis Factor-Alpha (TNF-.alpha.)
[0036] TNF-.alpha. is a pleiotropic cytokine that plays a central
role in inflammation. Increase in its expression is associated with
an up regulation in pro-inflammatory activity. Thus, compounds that
reduce the secretion of TNF-.alpha. protein by human epidermal
keratinocytes reduce the inflammatory response resulting in reduced
skin redness and irritation.
[0037] 5. Matrix Metalloproteinases (MMPs)
[0038] MMPs are extracellular proteases whose substrates include
the extracellular matrix proteins which comprise the skin dermal
compartment. MMP3 substrates include collagens, fibronectins, and
laminin, while MMP9 substrates include collagen VII, fibronectin,
and laminin. In aging skin, the these enzymes work to destroy the
proteins which provide support for the skin. Therefore, reduction
in the activity of these enzymes inhibits the destruction of these
proteins. Thus, compounds which inhibit the activity of MMPs will
result increased amounts of collagen and other dermal matrix
proteins.
B. DERIVATIVES AND MODIFICATION OF THE AROMATIC SKIN-ACTIVE
INGREDIENTS
[0039] Derivatives and modifications to the aromatic skin-active
ingredients of the present invention are also contemplated in the
context of the present invention. Non-limiting examples of
modifications that can be made to such ingredients include the
addition or removal of lower alkyls such as methyl, ethyl, propyl,
or substituted lower alkyls such as hydroxymethyl or aminomethyl
groups; carboxyl groups and carbonyl groups; hydroxyls; nitro,
amino, amide, and azo groups; sulfate, sulfonate, sulfono,
sulfhydryl, sulfonyl, sulfoxido, phosphate, phosphono, phosphoryl
groups, and halide substituents. Additional modifications can
include an addition or a deletion of one or more atoms of the
atomic framework, for example, substitution of an ethyl by a
propyl; and substitution of a phenyl by a larger or smaller
aromatic group. Alternatively, in a cyclic or bicyclic structure,
hetero atoms such as N, S, or O can be substituted into the
structure instead of a carbon atom.
C. COMPOSITIONS OF THE PRESENT INVENTION
[0040] 1. Combinations and Amounts of Ingredients
[0041] It is contemplated that the compositions of the present
invention can include any number of combinations of the aromatic
skin-active ingredients disclosed throughout this specification.
Additionally, the compositions can include any number of
combinations of additional ingredients described throughout this
specification. The concentrations of the aromatic skin-active
ingredients and additional ingredients can vary. In non-limiting
embodiments, for example, the compositions can include in their
final form, for example, at least about 0.0001%, 0.0002%, 0.0003%,
0.0004%, 0.0005%, 0.0006%, 0.0007%, 0.0008%, 0.0009%, 0.0010%,
0.0011%, 0.0012%, 0.0013%, 0.0014%, 0.0015%, 0.0016%, 0.0017%,
0.0018%, 0.0019%, 0.0020%, 0.0021%, 0.0022%, 0.0023%, 0.0024%,
0.0025%, 0.0026%, 0.0027%, 0.0028%, 0.0029%, 0.0030%, 0.0031%,
0.0032%, 0.0033%, 0.0034%, 0.0035%, 0.0036%, 0.0037%, 0.0038%,
0.0039%, 0.0040%, 0.0041%, 0.0042%, 0.0043%, 0.0044%, 0.0045%,
0.0046%, 0.0047%, 0.0048%, 0.0049%, 0.0050%, 0.0051%, 0.0052%,
0.0053%, 0.0054%, 0.0055%, 0.0056%, 0.0057%, 0.0058%, 0.0059%,
0.0060%, 0.0061%, 0.0062%, 0.0063%, 0.0064%, 0.0065%, 0.0066%,
0.0067%, 0.0068%, 0.0069%, 0.0070%, 0.0071%, 0.0072%, 0.0073%,
0.0074%, 0.0075%, 0.0076%, 0.0077%, 0.0078%, 0.0079%, 0.0080%,
0.0081%, 0.0082%, 0.0083%, 0.0084%, 0.0085%, 0.0086%, 0.0087%,
0.0088%, 0.0089%, 0.0090%, 0.0091%, 0.0092%, 0.0093%, 0.0094%,
0.0095%, 0.0096%, 0.0097%, 0.0098%, 0.0099%, 0.0100%, 0.0200%,
0.0250%, 0.0275%, 0.0300%, 0.0325%, 0.0350%, 0.0375%, 0.0400%,
0.0425%, 0.0450%, 0.0475%, 0.0500%, 0.0525%, 0.0550%, 0.0575%,
0.0600%, 0.0625%, 0.0650%, 0.0675%, 0.0700%, 0.0725%, 0.0750%,
0.0775%, 0.0800%, 0.0825%, 0.0850%, 0.0875%, 0.0900%, 0.0925%,
0.0950%, 0.0975%, 0.1000%, 0.1250%, 0.1500%, 0.1750%, 0.2000%,
0.2250%, 0.2500%, 0.2750%, 0.3000%, 0.3250%, 0.3500%, 0.3750%,
0.4000%, 0.4250%, 0.4500%, 0.4750%, 0.5000%, 0.5250%, 0.550%,
0.5750%, 0.6000%, 0.6250%, 0.6500%, 0.6750%, 0.7000%, 0.7250%,
0.7500%, 0.7750%, 0.8000%, 0.8250%, 0.8500%, 0.8750%, 0.9000%,
0.9250%, 0.9500%, 0.9750%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%,
1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%,
2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%,
3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%,
4.9%, 5.0%, 5.1%, 5.2%, 5.3%, 5.4%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9%,
6.0%, 6.1%, 6.2%, 6.3%, 6.4%, 6.5%, 6.6%, 6.7%, 6.8%, 6.9%, 7.0%,
7.1%, 7.2%, 7.3%, 7.4%, 7.5%, 7.6%, 7.7%, 7.8%, 7.9%, 8.0%, 8.1%,
8.2%, 8.3%, 8.4%, 8.5%, 8.6%, 8.7%, 8.8%, 8.9%, 9.0%, 9.1%, 9.2%,
9.3%, 9.4%, 9.5%, 9.6%, 9.7%, 9.8%, 9.9%, 10%, 11%, 12%, 13%, 14%,
15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%,
28%, 29%, 30%, 35%, 40%, 45%, 50%, 60%, 65%, 70%, 75%, 80%, 85%,
90%, 95%, or 99% or more, or any range or integer derivable
therein, of at least one of the aromatic skin-active ingredients or
additional ingredients. In non-limiting aspects, the percentage of
such ingredients can be calculated by weight or volume of the total
weight of the compositions. The concentrations can vary depending
on the desired effect of the compositions or on the product into
which the compositions are incorporated.
[0042] 2. Composition Vehicles
[0043] The compositions of the present invention can be formulated
into all types of vehicles. Non-limiting examples of suitable
vehicles include emulsions (e.g., water-in-oil,
water-in-oil-in-water, oil-in-water, oil-in-water-in-oil,
oil-in-water-in-silicone emulsions), creams, lotions, solutions
(both aqueous and hydro-alcoholic), anhydrous bases (such as
lipsticks and powders), gels, and ointments or by other method or
any combination of the forgoing as would be known to one of
ordinary skill in the art (Remington's, 1990). Variations and other
appropriate vehicles will be apparent to the skilled artisan and
are appropriate for use in the present invention. In certain
aspects, the concentrations and combinations of the ingredients be
selected in such a way that the combinations are chemically
compatible and do not form complexes which precipitate from the
finished product.
[0044] It is also contemplated that aromatic skin-active
ingredients and additional ingredients identified throughout this
specification can be encapsulated for delivery to a target area
such as skin. Non-limiting examples of encapsulation techniques
include the use of liposomes, vesicles, and/or nanoparticles (e.g.,
biodegradable and non-biodegradable colloidal particles comprising
polymeric materials in which the ingredient is trapped,
encapsulated, and/or absorbed-examples include nanospheres and
nanocapsules) that can be used as delivery vehicles to deliver such
ingredients to skin (see, e.g., U.S. Pat. No. 6,387,398; U.S. Pat.
No. 6,203,802; U.S. Pat. No. 5,411,744; Kreuter 1998).
[0045] Also contemplated are pharmaceutically-acceptable or
pharmacologically-acceptable compositions. The phrase
"pharmaceutically-acceptable" or "pharmacologically-acceptable"
includes compositions that do not produce an allergic or similar
untoward reaction when administered to a human. Typically, such
compositions are prepared either as topical compositions, liquid
solutions or suspensions, solid forms suitable for solution in, or
suspension in, liquid prior to use can also be prepared. Routes of
administration can vary with the location and nature of the
condition to be treated, and include, e.g., topical, inhalation,
intradermal, transdermal, parenteral, intravenous, intramuscular,
intranasal, subcutaneous, percutaneous, intratracheal,
intraperitoneal, intratumoral, perfusion, lavage, direct injection,
and oral administration and formulation.
[0046] 3. Products
[0047] The compositions of the present invention can be
incorporated into products. Non-limiting examples of products
include cosmetic products, food-based products, pharmaceutical
products, etc. By way of example only, non-limiting cosmetic
products include sunscreen products, sunless skin tanning products,
hair products, fingernail products, moisturizing creams, skin
benefit creams and lotions, softeners, day lotions, gels,
ointments, foundations, night creams, lipsticks, mascaras,
eyeshadows, eyeliners, cheek colors, cleansers, toners, masks, or
other known cosmetic products or applications. Additionally, the
cosmetic products can be formulated as leave-on or rinse-off
products.
[0048] 4. Additional Ingredients
[0049] Compositions of the present invention can include additional
ingredients. Non-limiting examples of additional ingredients
include cosmetic ingredients (both active and non-active) and
pharmaceutical ingredients (both active and non-active).
[0050] a. Cosmetic Ingredients
[0051] The CTFA International Cosmetic Ingredient Dictionary and
Handbook (2004) describes a wide variety of non-limiting cosmetic
ingredients that can be used in the context of the present
invention. Examples of these ingredient classes include: fragrances
(artificial and natural), dyes and color ingredients (e.g., Blue 1,
Blue 1 Lake, Red 40, titanium dioxide, D&C blue no. 4, D&C
green no. 5, D&C orange no. 4, D&C red no. 17, D&C red
no. 33, D&C violet no. 2, D&C yellow no. 10, and D&C
yellow no. 11), adsorbents, emulsifiers, stabilizers, lubricants,
solvents, moisturizers (including, e.g., emollients, humectants,
film formers, occlusive agents, and agents that affect the natural
moisturization mechanisms of the skin), water-repellants, UV
absorbers (physical and chemical absorbers such as paraaminobenzoic
acid ("PABA") and corresponding PABA derivatives, titanium dioxide,
zinc oxide, etc.), essential oils, vitamins (e.g., A, B, C, D, E,
and K), trace metals (e.g., zinc, calcium and selenium),
anti-irritants (e.g., steroids and non-steroidal
anti-inflammatories), botanical extracts (e.g., aloe vera,
chamomile, cucumber extract, ginkgo biloba, ginseng, and rosemary),
anti-microbial agents, antioxidants (e.g., BHT and tocopherol),
chelating agents (e.g., disodium EDTA and tetrasodium EDTA),
preservatives (e.g., methylparaben and propylparaben), pH adjusters
(e.g., sodium hydroxide and citric acid), absorbents (e.g.,
aluminum starch octenylsuccinate, kaolin, corn starch, oat starch,
cyclodextrin, talc, and zeolite), skin bleaching and lightening
agents (e.g., hydroquinone and niacinamide lactate), humectants
(e.g., glycerin, propylene glycol, butylene glycol, pentylene
glycol, sorbitol, urea, and manitol), exfoliants (e.g.,
alpha-hydroxyacids, and beta-hydroxyacids such as lactic acid,
glycolic acid, and salicylic acid; and salts thereof) waterproofing
agents (e.g., magnesium/aluminum hydroxide stearate), skin
conditioning agents (e.g., aloe extracts, allantoin, bisabolol,
ceramides, dimethicone, hyaluronic acid, and dipotassium
glycyrrhizate), thickening agents (e.g., substances which that can
increase the viscosity of a composition such as carboxylic acid
polymers, crosslinked polyacrylate polymers, polyacrylamide
polymers, polysaccharides, and gums), and silicone containing
compounds (e.g., silicone oils and polyorganosiloxanes).
[0052] b. Pharmaceutical Ingredients
[0053] Pharmaceutical ingredients are also contemplated as being
useful with the emulsion compositions of the present invention.
Non-limiting examples of pharmaceutical ingredients include
anti-acne agents, agents used to treat rosacea, analgesics,
anesthetics, anorectals, antihistamines, anti-inflammatory agents
including non-steroidal anti-inflammatory drugs, antibiotics,
antifungals, antivirals, antimicrobials, anti-cancer actives,
scabicides, pediculicides, antineoplastics, antiperspirants,
antipruritics, antipsoriatic agents, antiseborrheic agents,
biologically active proteins and peptides, burn treatment agents,
cauterizing agents, depigmenting agents, depilatories, diaper rash
treatment agents, enzymes, hair growth stimulants, hair growth
retardants including DFMO and its salts and analogs, hemostatics,
kerotolytics, canker sore treatment agents, cold sore treatment
agents, dental and periodontal treatment agents, photosensitizing
actives, skin protectant/barrier agents, steroids including
hormones and corticosteroids, sunburn treatment agents, sunscreens,
transdermal actives, nasal actives, vaginal actives, wart treatment
agents, wound treatment agents, wound healing agents, etc.
D. KITS
[0054] Kits are also contemplated as being used in certain aspects
of the present invention. For instance, a composition of the
present invention can be included in a kit. A kit can include a
container. Containers can include a bottle, a metal tube, a
laminate tube, a plastic tube, a dispenser, a pressurized
container, a barrier container, a package, a compartment, a
lipstick container, a compact container, cosmetic pans that can
hold cosmetic compositions, or other types of containers such as
injection or blow-molded plastic containers into which the
dispersions or compositions or desired bottles, dispensers, or
packages are retained. The kit and/or container can include indicia
on its surface. The indicia, for example, can be a word, a phrase,
an abbreviation, a picture, or a symbol.
[0055] The containers can dispense a pre-determined amount of a
composition. In other embodiments, the container can be squeezed
(e.g., metal, laminate, or plastic tube) to dispense a desired
amount of the composition. The composition can be dispensed as a
spray, an aerosol, a liquid, a fluid, or a semi-solid. The
containers can have spray, pump, or squeeze mechanisms. A kit can
also include instructions for using the kit and/or compositions.
Instructions can include an explanation of how to apply, use, and
maintain the compositions.
EXAMPLES
[0056] The following examples are included to demonstrate certain
non-limiting aspects of the invention. It should be appreciated by
those of skill in the art that the techniques disclosed in the
examples which follow represent techniques discovered by the
inventor to function well in the practice of the invention.
However, those of skill in the art should, in light of the present
disclosure, appreciate that many changes can be made in the
specific embodiments which are disclosed and still obtain a like or
similar result without departing from the spirit and scope of the
invention.
Example 1
Efficacy Data for the Aromatic-Skin Active Ingredients
[0057] The following Tables 2-4 provide data confirming the
efficacy of the aromatic skin-active ingredients identified in
Table 1 above:
TABLE-US-00002 TABLE 2 Aromatic Skin- Active Cox-1 Cox-2 LO MMP3
MMP9 TNF-.alpha. Ingredient Inhibition Inhibition Inhibition
Inhibition Inhibition Inhibition (alternate name) (0.020%) (0.001%)
(0.1%) (0.001%) (0.001%) (0.01%) Aldehyde C-11 -38.68% MOA
2,4-nonadien-1-al -21.15% -23.75% -19.87% 2-dodecenal (E) -24.98%
Aldehyde C-12 -27.64% Lauric Beta Ionone -19.82% 2,6-nonadien-1-al
-11.42% -17.58% -45.58% -20.34% -32.53% Vertenex .RTM. H.C. -18.50%
-37.86% Neofolione -27.46% -53.90% Precyclemone B -25.09% Cyclacet
-26.37% Melanol -20.45% Floralozone -33.20% Calone 1951 -21.26%
TABLE-US-00003 TABLE 3 Aromatic Skin-Active Ingredient Cox-2
Inhibition MMP9 Inhibition (alternate name) (0.001%) (0.01%) Leaf
Acetate -22.04% Dihydro-jasmone -32.33% -37.47% Romascone .RTM.
-23.31% Iso E super -20.80% Stemone -22.31% Polysantol -36.09%
4-methyl-3-decen-5-ol -28.09% Iso Cyclo Citral -31.58% -21.78%
3-hexen-1-ol (E) and (Z) -23.56% -23.82% Aldehyde C-18 -22.56%
-22.22% Ethylene Brassylate -20.55% -32.98% Cis-6-Nonenal -27.07%
-19.20% Herbanante -25.06% -26.84% Methyl Dihydro Jasmonate
-33.78%
TABLE-US-00004 TABLE 4 Aromatic Skin-Active Cox-1 Cox-2 LO
Antioxidant Ingredient Inhibition Inhibition Inhibition Properties
(alternate name) (0.001%) (0.001%) (0.001%) (0.001%) Citronellyl
Acetate -27.99% -20.93% Ethyl Linalool +23.62% Aldehyde C-14
-20.24%
Example 2
Assays to Assess Efficacy
[0058] The following assays were used to obtain the results
identified in Tables 2-4.
[0059] Antioxidant (AO) assay: An in vitro bioassay that measures
the total anti-oxidant capacity of compounds. The assay relies on
the ability of antioxidants in the sample to inhibit the oxidation
of ABTS.RTM. (2,2'-azino-di-[3-ethylbenzthiazoline sulphonate]) to
ABTS.RTM. .cndot.+ by metmyoglobin. The antioxidant system of
living organisms includes enzymes such as superoxide dismutase,
catalase, and glutathione peroxidase; macromolecules such as
albumin, ceruloplasmin, and ferritin; and an array of small
molecules, including ascorbic acid, .alpha.-tocopherol,
.beta.-carotene, reduced glutathione, uric acid, and bilirubin. The
sum of endogenous and food-derived antioxidants represents the
total antioxidant activity of the extracellular fluid. Cooperation
of all the different antioxidants provides greater protection
against attack by reactive oxygen or nitrogen radicals, than any
single compound alone. Thus, the overall antioxidant capacity may
give more relevant biological information compared to that obtained
by the measurement of individual components, as it considers the
cumulative effect of all antioxidants present in plasma and body
fluids. This assay relies on the ability of antioxidants in the
sample to inhibit the oxidation of ABTS.RTM.
(2,2'-azino-di-[3-ethylbenzthiazoline sulphonate]) to ABTS.RTM.
.cndot.+ by metmyoglobin. The capacity of the antioxidants in the
sample to prevent ABTS oxidation is compared with that of Trolox, a
water-soluble tocopherol analogue, and is quantified as molar
Trolox equivalents.
[0060] Using an Anti-oxidant Assay kit (#709001; Cayman Chemicals),
compounds were tested for their ability to inhibit oxidation of
substrates in vitro. Positive values reflect the ability of
compounds to inhibit oxidation and demonstrate anti-oxidant
capabilities.
[0061] Lipoxygenase (LO) assay: An in vitro lipoxygenase (LO)
inhibition assay. LOs are non-heme iron-containing dioxygenases
that catalyze the addition of molecular oxygen to fatty acids.
Linoleate and arachidonate are the main substrates for LOs in
plants and animals. Arachadonic acid may then be converted to
hydroxyeicosotrienenoic (HETE) acid derivatives, that are
subsequently converted to leukotirenes, potent inflammatory
mediators. This assay provides an accurate and convenient method
for screening lipoxygenase inhibitors by measuring the
hydroperoxides generated from the incubation of a lipoxygenase (5-,
12-, or 15-LO) with arachidonic acid.
[0062] Following manufacturer instructions for the Colorimetric LO
Inhibitor screening kit (#760700, Cayman Chemical), purified
15-lipoxygenase and test compounds were mixed in assay buffer and
incubated with shaking for 10 min at room temperature. Following
incubation, arachidonic acid was added to initiate the reaction and
mixtures incubated for an additional 10 min at room temperature.
Colorimetric substrate was added to terminate catalysis and color
progression was evaluated by fluorescence plate reading at 490 nm.
The percent inhibition of lipoxyganse activity was calculated
compared to non-treated controls to determine the ability of test
compounds to inhibit the activity of purified enzyme.
[0063] Cyclooxygenase (COX) assay: An in vitro cyclooxygenase-1 and
-2 (COX-1, -2) inhibition assay. COX is a bifunctional enzyme
exhibiting both cyclooxygenase and peroxidase activities. The
cyclooxygenase activity converts arachidonic acid to a hydroperoxy
endoperoxide (Prostaglandin G2; PGG2) and the peroxidase component
reduces the endoperoxide (Prostaglandin H2; PGH2) to the
corresponding alcohol, the precursor of prostaglandins,
thromboxanes, and prostacyclins. This COX Inhibitor Screening Assay
measures the peroxidase component of cyclooxygenases. The
peroxidase activity is assayed colorimetrically by monitoring the
appearance of oxidized N,N,N',N'-tetramethyl-p-phenylenediamine
(TMPD). This inhibitor screening assay includes both COX-1 and
COX-2 enzymes in order to screen isozyme-specific inhibitors.
[0064] Following manufacturer instructions for the Colormetric COX
(ovine) Inhibitor screening assay (#760111, Cayman Chemical),
purified cyclooxygnase enzyme (COX-1 or COX-2), heme and test
compounds were mixed in assay buffer and incubated with shaking for
15 min at room temperature. Following incubation, arachidonic acid
and colorimetric substrate were added to initiate the reaction and
incubated for an additional 15 min at room temperature with
shaking. Color progression was evaluated by fluoresecence plate
reading at 590 nm. The percent inhibition of COX-1 or COX-2
activity was calculated compared to non-treated controls to
determine the ability of test compounds to inhibit the activity of
purified enzyme.
[0065] Tumor necrosis factor alpha (TNF-.alpha.) assay: The
prototype ligand of the TNF superfamily, TNF-.alpha., is a
pleiotropic cytokine that plays a central role in inflammation.
Increase in its expression is associated with an up regulation in
pro-inflammatory activity. This bioassay analyzes the effect of
compounds on the production of TNF-.alpha. by human epidermal
keratinocytes. The endpoint of this assay is a spectrophotometric
measurement that reflects the presence of TNF-.alpha. and cellular
viability. The assay employs the quantitative sandwich enzyme
immunoassay technique whereby a monoclonal antibody specific for
TNF-.alpha. has been pre-coated onto a microplate. Standards and
samples are pipetted into the wells and any TNF-.alpha.. present is
bound by the immobilized antibody. After washing away any unbound
substances, an enzyme-linked polyclonal antibody specific for
TNF-.alpha. is added to the wells. Following a wash to remove any
unbound antibody-enzyme reagent, a substrate solution is added to
the wells and color develops in proportion to the amount of
TNF-.alpha. bound in the initial step using a microplate reader for
detection at 450 nm. The color development is stopped and the
intensity of the color is measured.
[0066] Subconfluent normal human adult keratinocytes (Cascade
Biologics) cultivated in EpiLife standard growth medium (Cascade
Biologics) at 37.degree. C. in 5% CO.sub.2, were treated with PMA
(10 ng/ml, Sigma Chemical, # P1585-1MG) and test compounds for 6
hours. PMA has been shown to cause a dramatic increase in
TNF-.alpha. secretion which peaks at 6 hours after treatment.
Following incubation, cell culture medium was collected and the
amount of TNF-a secretion quantified using a sanwhich enzyme linked
immuno-sorbant assay (ELISA) from R&D Systems (# DTA00C).
Following all manufacturer instructions, medium from treated cells
was incubated with antibodies directed against human TNF-.alpha.
which were bound to microtiter plates. The amount of TNF-.alpha.
protein was quantified by comparison of optical density units to
standard concentrations of purified TNF-.alpha. protein. Values are
calculated as % change in the amount of TNF-.alpha. protein
secreted between control and treated samples. Negative values
reflect the ability of test compounds to reduce the secretion of
TNF-.alpha. under conditions known to induce skin irritation (PMA
addition) compared to untreated controls.
[0067] Matrix metalloproteinase enzyme activity (MMP3; MMP9) assay:
An in vitro matrix metalloprotease (MMP) inhibition assay. MMPs are
extracellular proteases that play a role in many normal and disease
states by virtue of their broad substrate specificity. MMP3
substrates include collagens, fibronectins, and laminin; while MMP9
substrates include collagen VII, fibronectins and laminin. Using
Colorimetric Drug Discovery kits from BioMol International for MMP3
(AK-400) and MMP-9 (AK-410), this assay is designed to measure
protease activity of MMPs using a thiopeptide as a chromogenic
substrate (Ac-PLG-[2-mercapto-4-methyl-pentanoyl]-LG-OC2H5)5,6. The
MMP cleavage site peptide bond is replaced by a thioester bond in
the thiopeptide. Hydrolysis of this bond by an MMP produces a
sulfhydryl group, which reacts with DTNB
[5,5'-dithiobis(2-nitrobenzoic acid), Ellman's reagent] to form
2-nitro-5-thiobenzoic acid, which can be detected by its absorbance
at 412 nm (.epsilon.=13,600 M-1 cm-1 at pH 6.0 and above 7). Data
is reflected as % inhibition of the purified enzyme activity.
Negative values demonstrate the ability of test compounds to
inhibit the activity of MMPs compared to diluent controls.
Example 3
Compositions
[0068] Non-limiting examples of compositions of the present
invention that can include an aromatic skin-active ingredient are
described in Tables 5 and 6.
TABLE-US-00005 TABLE 5* Ingredient % Concentration (by weight)
Phase A Water 84.44 Xanthum gum 0.1 M-paraben 0.15 P-paraben 0.1
Citric acid 0.01 Phase B Cetyl alcohol 4.0 Glyceryl stearate + PEG
100 4.0 Octyl palmitate 4.0 Dimethicone 1.0 Tocopheryl acetate 0.2
Phase C** Aromatic Skin-Active 2.0 Ingredient(s) *Procedure for
making composition: Sprinkle Xanthum gum in water and mix for 10
min. Subsequently, add all ingredients in phase A and heat to
70-75.degree. C. Add all items in phase B to separate beaker and
heat to 70-75.degree. C. Mix phases A and B at 70-75.degree. C.
Continue mixing and allow composition to cool to 30.degree. C.
Subsequently, add phase C ingredient while mixing. **The aromatic
skin-active ingredients identified throughout this specification
can be incorporated into this composition. Additionally, any
combination of such ingredients (including 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,
27, 28, 29, 30, or more) can be incorporated into a single
composition. In such a case, the concentration ranges can be
modified as desired or needed.
TABLE-US-00006 TABLE 6* Ingredient % Concentration (by weight)
Phase A Water 78.6 M-paraben 0.2 P-paraben 0.1 Na2 EDTA 0.1 Shea
butter 4.5 Petrolatum 4.5 Glycerin 4.0 Propylene Glycol 2.0
Finsolve TN 2.0 Phase B Sepigel 305 2.0 Phase C** Aromatic
Skin-Active 2.0 Ingredient(s) *Add ingredients in phase A to beaker
and heat to 70-75.degree. C. while mixing. Subsequently, add the
phase B ingredient with phase A and cool to 30.degree. C. with
mixing. Subsequently, add phase C ingredient while mixing. **The
aromatic skin-active ingredients identified throughout this
specification can be incorporated into this composition.
Additionally, any combination of such ingredients (including 2, 3,
4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,
22, 23, 24, 25, 26, 27, 28, 29, 30, or more) can be incorporated
into a single composition. In such a case, the concentration ranges
can be modified as desired or needed.
Example 4
Determining Efficacy of the Compositions of the Present
Invention
[0069] The efficacy of compositions of the present inventions can
be determined by methods known to those of ordinary skill in the
art. The following are non-limiting procedures that can be used in
the context of the present invention. It should be recognized that
other testing procedures can be used, including, for example,
objective and subjective procedures.
[0070] Skin moisture/hydration can be measured by using impedance
measurements with the Nova Dermal Phase Meter. The impedance meter
measures changes in skin moisture content. The outer layer of the
skin has distinct electrical properties. When skin is dry it
conducts electricity very poorly. As it becomes more hydrated
increasing conductivity results. Consequently, changes in skin
impedance (related to conductivity) can be used to assess changes
in skin hydration. The unit can be calibrated according to
instrument instructions for each testing day. A notation of
temperature and relative humidity can also be made. Subjects can be
evaluated as follows: prior to measurement they can equilibrate in
a room with defined humidity (e.g., 30-50%) and temperature (e.g.,
68-72.degree. C.). Three separate impedance readings can be taken
on each side of the face, recorded, and averaged. The T5 setting
can be used on the impedance meter which averages the impedance
values of every five seconds application to the face. Changes can
be reported with statistical variance and significance.
[0071] Skin clarity and the reduction in freckles and age spots can
be evaluated using a Minolta Chromometer. Changes in skin color can
be assessed to determine irritation potential due to product
treatment using the a* values of the Minolta Chroma Meter. The a*
value measures changes in skin color in the red region. This is
used to determine whether a composition is inducing irritation. The
measurements can be made on each side of the face and averaged, as
left and right facial values. Skin clarity can also be measured
using the Minolta Meter. The measurement is a combination of the
a*, b, and L values of the Minolta Meter and is related to skin
brightness, and correlates well with skin smoothness and hydration.
Skin reading is taken as above. In one non-limiting aspect, skin
clarity can be described as L/C where C is chroma and is defined as
(a.sup.2+b.sup.2).sup.1/2.
[0072] Skin dryness, surface fine lines, skin smoothness, and skin
tone can be evaluated with clinical grading techniques. For
example, clinical grading of skin dryness can be determined by a
five point standard Kligman Scale: (0) skin is soft and moist; (1)
skin appears normal with no visible dryness; (2) skin feels
slightly dry to the touch with no visible flaking; (3) skin feels
dry, tough, and has a whitish appearance with some scaling; and (4)
skin feels very dry, rough, and has a whitish appearance with
scaling. Evaluations can be made independently by two clinicians
and averaged.
[0073] Clinical grading of skin tone can be performed via a ten
point analog numerical scale: (10) even skin of uniform, pinkish
brown color. No dark, erythremic, or scaly patches upon examination
with a hand held magnifying lens. Microtexture of the skin very
uniform upon touch; (7) even skin tone observed without
magnification. No scaly areas, but slight discolorations either due
to pigmentation or erythema. No discolorations more than 1 cm in
diameter; (4) both skin discoloration and uneven texture easily
noticeable. Slight scaliness. Skin rough to the touch in some
areas; and (1) uneven skin coloration and texture. Numerous areas
of scaliness and discoloration, either hypopigmented, erythremic or
dark spots. Large areas of uneven color more than 1 cm in diameter.
Evaluations were made independently by two clinicians and
averaged.
[0074] Clinical grading of skin smoothness can be analyzed via a
ten point analog numerical scale: (10) smooth, skin is moist and
glistening, no resistance upon dragging finger across surface; (7)
somewhat smooth, slight resistance; (4) rough, visibly altered,
friction upon rubbing; and (1) rough, flaky, uneven surface.
Evaluations were made independently by two clinicians and
averaged.
[0075] Skin smoothness and wrinkle reduction can also be assessed
visually by using the methods disclosed in Packman et al. (1978).
For example, at each subject visit, the depth, shallowness and the
total number of superficial facial lines (SFLs) of each subject can
be carefully scored and recorded. A numerical score was obtained by
multiplying a number factor times a depth/width/length factor.
Scores are obtained for the eye area and mouth area (left and right
sides) and added together as the total wrinkle score.
[0076] Skin firmness can be measured using a Hargens ballistometer,
a device that evaluates the elasticity and firmness of the skin by
dropping a small body onto the skin and recording its first two
rebound peaks. The ballistometry is a small lightweight probe with
a relatively blunt tip (4 square mm-contact area) was used. The
probe penetrates slightly into the skin and results in measurements
that are dependent upon the properties of the outer layers of the
skin, including the stratum corneum and outer epidermis and some of
the dermal layers.
[0077] Skin softness/suppleness can be evaluated using the Gas
Bearing Electrodynamometer, an instrument that measures the
stress/strain properties of the skin. The viscoelastic properties
of skin correlate with skin moisturization. Measurements can be
obtained on the predetermined site on the cheek area by attaching
the probe to the skin surface with double-stick tape. A force of
approximately 3.5 gm can be applied parallel to the skin surface
and the skin displacement is accurately measured. Skin suppleness
can then be calculated and is expressed as DSR (Dynamic Spring Rate
in gm/mm).
[0078] The appearance of lines and wrinkles on the skin can be
evaluated using replicas, which is the impression of the skin's
surface. Silicone rubber like material can be used. The replica can
be analyzed by image analysis. Changes in the visibility of lines
and wrinkles can be objectively quantified via the taking of
silicon replicas form the subjects' face and analyzing the replicas
image using a computer image analysis system. Replicas can be taken
from the eye area and the neck area, and photographed with a
digital camera using a low angle incidence lighting. The digital
images can be analyzed with an image processing program and the are
of the replicas covered by wrinkles or fine lines was
determined.
[0079] The surface contour of the skin can be measured by using the
profilometer/Stylus method. This includes either shining a light or
dragging a stylus across the replica surface. The vertical
displacement of the stylus can be fed into a computer via a
distance transducer, and after scanning a fixed length of replica a
cross-sectional analysis of skin profile can be generated as a
two-dimensional curve. This scan can be repeated any number of
times along a fix axis to generate a simulated 3-D picture of the
skin. Ten random sections of the replicas using the stylus
technique can be obtained and combined to generate average values.
The values of interest include Ra which is the arithmetic mean of
all roughness (height) values computed by integrating the profile
height relative to the mean profile height. Rt which is the maximum
vertical distance between the highest peak and lowest trough, and
Rz which is the mean peak amplitude minus the mean peak height.
Values are given as a calibrated value in mm. Equipment should be
standardized prior to each use by scanning metal standards of know
values. Ra Value can be computed by the following equation:
R.sub.a=Standardize roughness; l.sub.m=the traverse (scan) length;
and y=the absolute value of the location of the profile relative to
the mean profile height (x-axis).
[0080] In other non-limiting aspects, the efficacy of the
compositions of the present invention can be evaluated by using a
skin analog, such as, for example, MELANODERM.TM.. Melanocytes, one
of the cells in the skin analog, stain positively when exposed to
L-dihydroxyphenyl alanine (L-DOPA), a precursor of melanin. The
skin analog, MELANODERM.TM., can be treated with a variety of bases
containing the compositions and whitening agents of the present
invention or with the base alone as a control. Alternatively, an
untreated sample of the skin analog can be used as a control.
[0081] Oxygen Radical Absorption (or Absorbance) Capacity (ORAC) of
the aromatic skin-active ingredients and compositions can also be
assayed by measuring the antioxidant activity of such ingredients
or compositions. This assay can quantify the degree and length of
time it takes to inhibit the action of an oxidizing agent such as
oxygen radicals that are known to cause damage cells (e.g., skin
cells). The ORAC value of the aromatic skin-active ingredients and
compositions can be determined by methods known to those of
ordinary skill in the art (see U.S. Publication Nos. 2004/0109905
and 2005/0163880; Cao et al. (1993)), all of which are incorporated
by reference). In summary, the assay described in Cao et al. (1993)
measures the ability of antioxidant compounds in test materials to
inhibit the decline of B-phycoerythrm (B-PE) fluorescence that is
induced by a peroxyl radical generator, AAPH.
[0082] All of the aromatic skin-active ingredients, compositions,
or methods disclosed and claimed in this specification can be made
and executed without undue experimentation in light of the present
disclosure. While the aromatic skin-active ingredients,
compositions, or methods of this invention have been described in
terms of particular embodiments, it will be apparent to those of
skill in the art that variations may be applied to the aromatic
skin-active ingredients, compositions, or methods and in the steps
or in the sequence of steps of the method described herein without
departing from the concept, spirit and scope of the invention.
REFERENCES
[0083] The following references, to the extent that they provide
exemplary procedural or other details supplementary to those set
forth herein, are specifically incorporated herein by reference.
[0084] U.S. Pat. No. 5,411,744 [0085] U.S. Pat. No. 6,203,802
[0086] U.S. Pat. No. 6,387,398 [0087] U.S. Patent Publn.
2004/0109905 [0088] U.S. Patent Publn. 2005/0163880 [0089] Cao et
al., Free Radic. Biol. Med., 14:303-311, 1993. [0090] International
Cosmetic Ingredient Dictionary, 10th edition, 2004. [0091] Kreuter,
J. Microencapsulation, 5:115-127, 1988. [0092] Organic Chemistry,
5.sup.th Ed. [0093] Packman and Gams, J. Soc. Cos. Chem., 29:70-90,
1978. [0094] Remington's Pharmaceutical Sciences, 18th Ed. Mack
Printing Company, 1289-1329, 1990.
* * * * *