Note: Descriptions are shown in the official language in which they were submitted.
CA 02309179 2000-OS-04
WO 00/13661 PCTNS99/~0ZI54
METHOD AND COMPOSITIONS FOR REDUCING
DERMATOLOGICAL AGING AND FOR REDUCING BRUISING
1. Field of the Invention
The present invention relates to topical compositions and methods
of using same for improving overall dermatoiogical health. The present
invention also relates to compositions for reducing susceptibility to bruising
and for decreasing the healing time for bruises that occur and to methods
for using these compositions. The present invention further relates to
topical compositions to alleviate dermatological symptoms associated with
hormonal aging and methods for using same.
2. Description of the Related Art
Aging of the skin results from the synergistic effects of intrinsic aging
(due to age and genetic factors), photoaging (due to exposure to ultraviolet
radiation), and, for women, hormonal aging (due to estrogen deficiency in
peri-menopausal and menopausal women.) Such dermatological aging
manifests as skin wrinkles, pigmentation/age spots, sallow skin, sagging
skin, thinning of skin, a decrease in skin's elasticity and resilience. One
cause of the foregoing manifestations of dermatologicai aging is a net loss
of collagen fibers in skin. This net loss of skin collagen fibers results in
thinning of the dermis. Because the dermis acts to "cushion" the force of
impact, this decrease in the thickness of the dermis can result in increased
bruising.
In addition, some women also experience an increase in acne
because of these hormonal changes.
A need exists for a composition and method that will retard or
reverse the negative dermatological effects associated with hormonal
aging. A further need exists for a composition and method that will
accomplish the foregoing with minimal adverse effects.
SUBSTITUTE SHEET (RULE 26)
*rB
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/20854
PCT publication WO 98/21946 to Wurtman et al. (the disclosure ot--
which is incorporated herein by reference) provides dietary supplements
that include phytoestrogen compounds, and either (a) remedial
carbohydrates, (b) choline compounds or (c) both.
PCT publication WO 98/56373 to Gorbach (the disclosure of which
is incorporated by reference herein) provides topical compositions that
utilize up rifled isoflavonoids, such as genistein, daidzein, biochanin A,
formononetin, O-desmethylangolensin, glycitin, and equol. Gorbach also
10 provides topical compositions having between 1 and 40mg of ua rued
isoflavones per gram of base (i.e. 0.1 wt% to 4 wt%) for treating and
preventing wrinkles. Gorbach defines "purified isoflavonoid" as an
isoflavonoid in a more concentrated form than occurs in plants.
U.S. Patent No. 5,166,132 to Gordon provides topical compositions
having an improved enzyme-modified casein solution that are useful for
healing and relieving bruising.
BRIEF SUMMARY OF THE INVENTION
It is an object of the present invention to provide topical
compositions and methods to reduce dermatological aging.
It is another object of the present invention to provide topical
compositions and methods to reduce susceptibility to bruising.
It is further an object of the present invention to provide topical
compositions and methods to reduce the severity of and healing period for
bruises that do manifest.
2
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/20854 ,
DETAILED DESCRIPTION OF THE INVENTION - -
A "topical composition" as used herein refers to a composition
intended to be directly applied or spread on the surtace of skin. An
"effective amount" means an amount of a compound or a composition
sufficient to induce a positive change in the skin condition. A
"physiologically acceptable vehicle" or a "suitable topical vehicle" refers to
a
drug, cosmetic, medicament or inert ingredient that is suitable for use in
direct contact with human tissues without undue toxicity. All percentages
refer to weight percent, based on the total weight of the topical
composition.
The first principal component of the present compositions is a
phytoextract. The phytoextract is preferably a phytoestrogen and, more
preferably, either a {1) isofiavone, (2) steroidal, (3) sterol, (4) coumestan,
(5) lignan, or (6) any mixture thereof.
The term "phytoextract" as used herein encompasses all such
compounds that occur naturally in plants regardless of whether the actual
compound used in the present invention is extracted from plant sources or
manmade. As stated above, it is preferred that the phytoextract is a
phytoestrogen. Preferably, the phytoextract is derived from plant sources.
in the more preferred embodiment, the phytoextract is a phytoestrogen that
is naturally derived. Alternatively, the phytoextract may be synthetically
derived. "Phytoestrogen" as used herein refers to compounds that are
either (a) known to exhibit an estrogen-type effect or (b) specifically set
forth herein as a phytoestrogen.
Exemplary phytoextracts and their sources are set forth below in
Table 1.
3
*rB
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/20854
TABLE 1 - -
Ph toextract Active Source
Se etalins B, C, and D Vaccaria segetalis.
Isoflavone 6-PrenylisocaviuninSopubia delphinifolia
3'-Prenyl-4'methoxy-isoflavone-7-O-~i-D-
2'O- -coumaro I luco ranoside
Kaempferol, Fennel
-Sitosterol, (Foeniculum vulgare)
Cimifugin or Macrotin, Black Cohosh
Cimigenol or Cimifugol, (Cimifuga racemosa)
Cimigoside or Cimigenol
Xyloside, Formononetin
Isoferulic acid, Cimifu oside
Daidzein, Genistein, Equol Soy
GI cine Max
Liqcoumarin, Licorice
6-Acetyl-5-hydroxy-4-methylcoumarin,(Gtycyrrhiza glabra)
Formononetin, Glabridin, Hispaglabridin-A,
His a labridin-B, Isoli uiriti
enin
Genistin, Biochanin A, Alfalfa
Coumesterol, Formononetin Medica o sativa
p-Sitosterol, Bourbon
Biochanin-A
~i-sitosterol, Beer
Genistein,
Daidzein
-Sitosterol, Saw Palmetto
Naringenin Eucalyptus,
Citrus Fruits, e. . Oran
es, Lemons
Humulone, Hops
Xanthohumol,
Lactaric acid
Coumestans, Sunflower
25-Dehydro-sitostanol,
23-Dehydro-p-sitosterol,
Ph tosterols
Estradiol, Estrone Pomegranate
Phytosterol
-Sitosterol
Phytosterol, Coumesterol, Brussel sprouts
Indole-3-
Carbinol, Quercitin
Diosgenin, DHEA Yam
(Dioscorea Species)
Biochanin A, Formononetin, Red Clover
Genistin,
Coumesterol Trifolium ratense
Matairesinol Palm
Enterodiol, Enterolactone
Brassicasterol, Campesterol, Canola
p-Sitosterol,
Sti masterol
Zearalenone sulfate Fusarium species
Biochanin A Le umes
4
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/20854
Fur~anoid Lignans Chaparral
Larrea tridentata
Matairesinol R a
The more preferred phytoextracts are phytoestrogens, such as
daidzein, daidzin, acetyl daidzin, malonyl daidzin, glycitin, acetyl glycitin,
malonyl glycitin, glycitein, genistin, acetyl genistin, malonyi genistin,
5 genistein, equol, and any mixture thereof. The most preferred
phytoextracts are daidzein, glycitein, genistein, equol and any mixture
thereof. When the phytoextract is daidzein, glycitein, genistein, equol, and
any mixture thereof, the topical composition preferably comprises from
about 0.01 wt% to about 0.1 wt% phytoextract, more preferably from about
0.015 wt% to about 0.08 wt% phytoextract, and most preferably from about
0.02 wt% to 0.072 wt% phytoextract.
Examples of preferred plant sources include soy, soy bean, red
clover, pomegranate, saw palmetto, canola, and any mixture thereof.
In addition to the phytoextract component, the present invention
preferably includes a secondary component. The secondary component is
selected from one or more of the following twelve groups.
20 1. An estrogen synthetase stimulatina compound: Examples of such a
compound include caffeine andlor derivatives thereof, and any mixture
thereof. Caffeine is the more preferred of such compounds.
2. A compound caeable of inhibitina 5 alpha-reductase activity: Examples
of such a compound include linolenic acid, linoleic acid, finasteride, and
any mixture thereof.
3. An exfoliation nromotina compound: Suitable examples include alpha
hydroxy acids; beta hydroxy acids; oxa acids as disclosed in U.S. Patent
No. 5,847,003 (the disclosure of which is incorporated by reference
5
CA 02309179 2000-OS-04
WO 00/13661 PCTNS99/20854
herein); oxa diacids as disclosed in U.S. Patent No. 5,834,513 (the ~ ---
disclosure of which is incorporated by reference herein); mechanical
exfoliation compounds, such as bamboo exfoliant extract; salicylic acid;
benzoyl peroxide; alpha-keto acids, such as pyruvic acid, 2-oxopropanoic
acid, 2-oxobutanoic acid, and 2-oxopentanoic acid; and any mixture
thereof.
The preferred exfoliation promoting compounds are lactic acid,
glycolic acid, 3,fi,9-trioxaundecanedioic acid, and any mixture thereof.
10 When present invention includes an exfoliation promoting compound, the
composition comprises about 1 wt% to 20 wt%, preferably 1 wt% to about
wt%, more preferably about 4 wt% to about 10 wt% acid, and most
preferably about 4 wt% of the exfoliation promoting compound.
15 4. An ultraviolet (UV) light protectinq/sunscreen agent: Examples include
organic and inorganic sunscreens, such as titanium dioxide, zinc oxide,
methyl benzylidene camphor and/or its derivatives, octocrylene,
anthranilates, benzophenones, butylmethoxydibenzoylmethane
(avobenzone), naphtholsulphonates, benzoic acid derivatives, salicylates,
cinnamic acid derivatives, and mixtures thereof. Of these,
butylmethoxydibenzoylmethane (PARSOL 1789), octocrylene,
octylsalicylate, octylmethoxycinnamate and oxybenzone, and mixtures
thereof are preferred. Butylmethoxydibenzoylmethane or avobenzone
(PARSOL 1789), oxybenzone and octylmethoxycinnamate, and mixtures
25 thereof are most preferred. In addition, U.S. Patent No. 5,824,702, to Wei
(the disclosure of which is incorporated by reference herein) provides that
genistein exhibits protective activity against ultraviolet induced skin
photodamage and cancer. Co-formulation with an ultraviolet light
protecting/sunscreen agent is particularly desirable when the present
invention is prepared for consumers who engage in outdoor activities.
6
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/20854
5. Retinoids: Examples of suitable retinoids include retinol, retinoic acid, --
retinyi palmitate, retinyl propionate, retinyl acetate, isotretinoin as well
as
synthetic retinoid mimics, and derivatives of the foregoing.
6. Hirsutism inhibiting agents: Examples of such agents include y-linolenic
acid, linoleic acid, and derivatives thereof.
7. Barrier function enhancing agents: Examples include ceramides,
essential fatty acids and their esters, especially glycerides, a-hydroxy fatty
acids and their esters derived with alkanols through carboxylic hydroxyl or
with other fatty acids at the omega-hydroxyl, the latter type being most
preferred, with phospholipids, cholesterol and its esters, such as
cholesteryl hemisuccinate and cholesteryl phosphate of which cholesterol
phosphate and essential fatty acids are most preferred, cholestanol and its
derivatives. The barrier function enhancing agent can be added to a
topical composition either as singular molecular entities or as a complex
mixture of lipids derived from either synthetic, animal or plant sources.
8. Collagen enhancing agents: These agents prevent skin sagging by
promoting a net increase in collagen, either by reducing collagen
breakdown or by promoting collagen formation. Examples of such
inhibitors include Clara extract (Sophora augustifolia), ascorbyl-phoshoryl-
cholesterol, ascorbic acid, ascorbic acid derivatives, and any mixtures
thereof.
9. Elastase inhibitors: Examples of these inhibitors include Honeysuckle
extract (Lonicera caprifolium). These inhibitors act to prevent sagging of
the skin.
10. Skin lightening aqe,nts: Examples include kojic acid, hydroquinone,
licorice derivatives, ascorbic acid/ascorbic acid derivatives (e.g.
magnesium ascorbyl phosphate), arbutin, bearberry (Arctosraphylos uva
7
*rB
CA 02309179 2000-OS-04
WO 00/13661 PCTNS99/20854
ursi), Glycyrrhiza glabra and its derivatives, Chlorella vulgaris extract, and-
-
any mixture thereof.
11. Antioxidants: Examples include compounds having phenolic
5 hydroxy functions, such as ascorbic acid, ascorbic acid derivatives, galfic
acid derivatives (e.g. propyl gallate); ferulic acid derivatives (e.g. ethyl
ferulate, sodium ferulate); nitrones; N-tertbutyl-nitrone; I-(4-pyridyl-1-
oxide)-
N-tertbutyl-nitrone; curcumin, tetrahydrocurcumin; 6-hydroxy-
2,5,7,tetramethylchroman-2-carboxylic acid; uric acid; reductic acid; tannic
acid; rosmarinic acid; tocopherol and its derivatives; catechins; and any
mixtures thereof. Other suitable antioxidants are those that have one or
more thiol functions (-SH), in either reduced or non-reduced form, such as
glutathione, lipoic acid, thioglycolic acid, and other sulfhydryl compounds.
The antioxidant may be inorganic, such as sulfites, bisulfites, metabisulfite,
or other inorganic salts and acids containing sulfur.
12. Skin coolin4 comaounds: Examples include menthol, menthyl glycerol,
asymmetrical carbonates, thiocarbonates and urethanes, N-substituted
carboxamides, ureas or phosphine oxides, menthyl lactate, menthone
20 glycerine acetal, and any mixtures thereof. Since many women experience
"hot flashes/flushes" during perimenopause, coformulation with skin
cooling compounds is particularly desirable when providing topical
compositions of the present invention for such women.
25 The secondary component enhances the dermatological benefits
achieved by the phytoextract. It is more preferred that the compositions of
the present invention include at least two secondary components with each
secondary component being selected from a different group. Table 2,
below, sets forth examples of such preferred combinations.
8
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/20854
TABLE 2 - --
Examples of combinations of phytoestrogen with secondary component.
Formula Number 1 2 3 4 5 6 7 8 9 10 11 12
Phytoestrogen X X X X X X X X X X X X
Glycolic Acid X X X X X
Lactic Acid X X
Oxa Acid X X
Retinol X X X X X
Ascorbyl- X X X
phosphoryl-
cholesterol
Ascorbic Acid X X X X
Octylmethoxycin-X X X X X X X X X X X
narrate
Oxybenzone X X X X X X X X X X X
Avobenzone X X X X X X X X X
Licorice root X X X
Tetrahydro- X X
curcumin
Nitric Oxide X X
Synthase Inhibitor
The compositions of the present invention can include other
cosmetic and pharmaceutical actives and excipients. Such suitable
cosmetic and pharmaceutical agents include, but are not limited to,
antifungals, vitamins, anti-inflammatory agents, antimicrobials, analgesics,
nitric oxide synthase inhibitors, insect repellents, self-tanning agents,
surfactants, moisturizers, stabilizers, preservatives, antiseptics,
thickeners,
lubricants, humectants, chelating agents, skin penetration enhancers,
emollients, fragrances and colorants.
9
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/?,0854
Examples of suitable thickening agents include xanthan gum, - --
hydroxypropyi cellulose, hydroxyethyl cellulose, carbomer, gum acacia,
Seppigel 305 (available from Seppic Co., France), and magnesium
aluminum silicate.
10
The topical compositions of the present invention can include, and
their utility can be enhanced by, humectants, such as urea, pyrrolidone
carboxylic acid, amino acids, sodium hyaluronate, certain polyols and other
compounds with hygroscopic properties.
Topical compositions of the present invention can also include one
or more of the following:
(i) vitamins, such as any B vitamin; 1,25-dihydroxy vitamin D3;
15 vitamin K; tocopherol and its derivatives; tocotrienols and their
derivatives;
nicotinic acid and its esters; pantothenic acid and it esters; panthenol;
folic
acid and its derivatives; phytic acid; ascorbic acid and its derivatives;
vitamin A and its derivatives; and any mixtures thereof;
20 (ii) antifungals, such as tolnaftate and ketoconazole;
(iii) self-tanning agents, such as dihydroxyacetone and lawsone;
(iv) anti-microbial agents, such as erythromycin and tetracycline;
(v) topical analgesics, such as lidocaine, benzocaine, butacaine,
tetracaine, clove oil and eugenol;
(vi) anti-inflammatory agents may be included in topical
30 compositions of the present invention. These anti-inflammatory agents are
used at concentrations from about 0.025 wt% to about 10 wt%, preferably,
about 0.5 wt% to about 1 wt%, with the concentration of the anti-
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/20854
inflammatory adjusted upward or downward depending upon the potency-=
of the utilized agents. Examples include hydrocortisone, prednisone,
prednisolone, aspirin, aspirin derivatives, aloe vera, willow bark,
chamomile, and mixtures thereof;
(vii) nitric oxide synthase inhibitors that reduce skin redness,
vasodilation and inflammatory reactions, especially in response to
electromagnetic and ionizing radiation or to the action of chemically or
biochemically aggresive compounds can be included in the present
invention. The nitric oxide synthase inhibitors are more preferably selected
from the group including guanidine derivatives, especially
monoaminoguanidine and methylguanidine, L-arginine derivatives,
especially NG-nitro-L-arginine and its esters, NG-monomethyl-L-arginine,
2-iminopiperidines, asymmetric dimethyl arginine (ADMA), boronic acid
analog of L-arginine (Boroarg-OH~2HC1), and other 2-
iminoazaheterocycles;
(viii) insect repellents, such as aliphatic, cyclic or aromatic amides,
citronella oil, terpineol, cineole, neem oil, terephthalic acid and its
esters,
ethyl butylacetylaminopropionate and N,N-diethyl-m-toluamide (DEET)
may be included in the present invention. Coformulation with insect
repellents can be particularly desirable when the present invention is used
to prevent bruising. For those who engage in vigorous outdoor activities,
such as hiking and other sports, having an insect repellent incorporated
into the present invention provides a convenient two-in-one preventative
measure.
The vehicle can comprise most conventional emollients including
mineral oil, petrolatum, paraffin, ceresin, ozokerite, microcrystralline wax,
perhydrosqualene dimethyl polysiloxanes, methylphenyl polysiloxanes,
silicone-glycol copolymers, triglyceride esters, acetylated monoglycerides,
ethoxylated glycerides, alkyl esters of fatty acids, fatty acids and alcohols,
11
*rB
CA 02309179 2000-OS-04
WO 00/13661 PCTNS99/20854
lanolin, lanolin derivatives, polyhydric alcohol esters, sterols, beeswax - --
derivatives, polyhydric alcohols and polyethers, and amides of fatty acids.
The emulsifiers can be cationic, anionic, nonionic, amphoteric, or a
combination thereof. Nonionic emulsifiers are preferred. Exemplary
nonionic emulsifiers are commercially available sorbitans, alkoxylated fatty
alcohols and alkyl polyglycosides. Anionic emulsifiers may include soaps,
alkyl sulfates, monoalkyl and dialkyl phosphates, alkyl sulphonates and
acyl isothionates.
The preservatives suitable for use with the present compositions
include alkanols, especially ethanol and benzyl alcohol, parabens,
sorbates, benzoic acid/benzoates, urea derivatves, and isothiazolinones.
15 The general activity and mildness to skin of the present topical
compositions can also be enhanced by neutralization to pH about 3.5 to
about 7.0, most preferably from pH about 3.7 to about 5.6, with one or
more of ammonium hydroxide, potassium hydroxide, sodium hydroxide,
arginine or other amino acids, andlor triethanolamine.
The utility of the present topical compositions can also be enhanced
by certain chelating agents incorporated into the composition at levels from
about 0.01 % to about 25% by weight, more preferably from about 0.5% to
10%, and most preferably from about 1 % to about 5%. Suitable examples
25 of chelating agents include those that have a high affinity for zinc,
calcium,
magnesium, iron andlor copper ions, such as ethylene-diamine-tetra-acetic
acid.
The topical compositions of the present invention can be further
30 formulated according to procedures known in the art to provide cosmetic
compositions such as emulsions, gels, creams, lotions, ointments, pastes,
sticks, cakes, pencils, essences and serums as well as other topical
12
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/20854 .,
cosmetic vehicles. It is also contemplated that topical compositions of the-
present invention can be incorporated into delivery systems such as
liposomes and topical patches, tapes, and sprays.
5 The topical compositions of the present invention are useful to
improve the aesthetic appearance of skin by any one of the following
methods:
1. Reducing dermatological aging, particularly dermatological
aging due to hormonal aging;
2. Decreasing skin fragility;
3. Preventing and reversing loss of collagen;
4. Preventing skin atrophy;
5. Promoting/accelerating cell turnover;
6. Providing cushion for blood vessels;
7. Improving skin texture;
8. Decreasing fine lines and wrinkles;
9. Improving skin tone;
10. Enhancing skin thickness;
11. Decreasing pore size;
12. Minimizing skin discoloration;
13. Restoring skin luster;
14. Minimizing signs of fatigue;
15. Reducing acne;
16. Decreasing susceptibility to bruising; and
17. Decreasing severity of bruising;
18. Decreasing time required for healing of bruises.
The present invention also includes methods by which these
compounds can be used to address the aforementioned skin conditions.
Such methods include topically applying an effective amount of the
composition of the present invention to areas of the skin, typically once or
twice daily. When the present invention is used to improve the overall
13
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/20854
aesthetic appearance of skin, the preferred areas of application include the
face and neck areas. When the present invention is used to reduce
susceptibility, severity and healing time of bruises, preferred areas of
application include hands, arms (particularly, forearms), legs (particularly,
lower leg areas), hips and any other areas subject to impact.
EXAMPLE 1
Thirty-seven women participated in a twelve week clinical study to
evaluate the efficacy of a topical composition, Sample A, in increasing the
thickness of the skin. The women treated one forearm with a test product
for twelve weeks. The arm to be treated (right or left) was assigned
randomly as the test area. Treatment was once every morning and sample
A was applied to the test area.
SAMPLE A
Ingredients wt%
lactic acid (85%) 4.71
soy extract (0.08%) 25.00
vehicle qs
20 The skin was then assessed visually at four weeks and at eight
weeks. Visual improvements of the treated arm were very evident. At four
weeks, the skin looked and felt smoother. The skin also appeared brighter.
At eight weeks, pigment discolorations looked lighter, and the skin had a
much better overall appearance. If the treated skin was laterally
compressed, the treated skin was far more resistant to compression.
Untreated skin compressed easily, resulting in visible crinkling.
It is believed that the resistance to compression exhibited by the
treated skin was the result of the epidermis and dermis becoming
30 "plumper" or thicker. The resulting increase in the thickness is believed
to
be result of activity of the lactic acid, the soy extract, or the combination
of
the two materials.
14
CA 02309179 2000-OS-04
WO 00/13661 PCTNS99/20854
EXAMPLE 2
Since thicker skin provides more "cushion," which might result in
less of a bruise from an impact or a pinch, the following twelve week study
was conducted to determine the efficacy of the present invention to reduce
the susceptibility of the skin to bruising.
The test utilized Sample A set forth above. Fifteen of the thirty-
seven women who participated in the test discussed in Example 1, above,
agreed to have their arms bruised at the twelve-week time point. All of
these women were post-menopausal.
The volar forearm was bruised using a pinch method. The skin was
given a calibrated pinch using Lange Skinfold Calipers. Both treated and
untreated volar forearms were pinched approximately two inches from the
elbow flex region.
The women returned to the laboratory at one day, four days, and
seven days after bruising. Minolta chromameter L-a-b measurements (an
objective measurement of skin color) were taken prior to bruising and on
the post-bruising follow-up days. Each woman also completed a self-
assessment questionnaire on the evaluation days.
Four days post-bruising was selected as the best day for bruise
25 assessments. Not all bruises appeared the first day after bruising, but all
bruises appeared within four days of trauma. Furthermore, of those
bruises that appeared early (one day post-trauma) some had completely
resolved seven days later. Therefore, day four post-bruising was selected
as the best time point to assess bruises.
L-a-b Color Measurements of Bruises
Chromameter measurements done in the L-a-b mode assessed
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/20854
three color components of the bruise color. The "L" value is an assessment
of light/dark. The "a" value is an assessment of redlgreen. The "b" value is
an assessment of yellow/blue. The following are the average change from
baseline (normal skin color) values obtained for "L", "a" and "b".
Chanae from Baseline Values - 4 Days Post-Bruising
Treated Untreated
L(Light) -1.1 -2.9
a (red) 0.26 2.02
b (yellow) 1.7 2.8
The higher the "L" value the lighter the skin. Therefore, the
untreated bruised skin was darker (or more bruised) than the treated
bruised skin. The "a" value increases with greater redness. Untreated
bruises were redder than treated bruises. The yellow component of the
bruise, the "b" value, is more yellow with a greater number. The "b" value
can also be a blue measurement, however, most of the values obtained
were in the yellow range (positive) of the scale. The average "b" value for
untreated skin was greater for untreated skin than treated skin.
The majority of the panelists had less bruising on the treated arm.
The following chart shows the number of panelists with better "L" (lighter),
"a" (less red) or "b" (less yellow) values for the treated or untreated arm:
Number of Panelist with Better Values - Day 4 Post-Bruising
Treated Untreated
Lighter(L) 11 4
Less Red (a) 10 5
Less Yellow (b) 11 4
Tables with individual data for "L", (Table 3), "a" (Table 4), and "b"
(Table 5) are set forth below.
16
CA 02309179 2000-05-04
WO 00/13661 PCT/US99/20854 ._
TABLE 3 - --
Change from Baseline in "L" Value (Bruise Darkness) - Day 4 Post-Bruising
Subject Treated Arm Untreated Which Better
# Arm
1 -6.9 -5.5 U
2 -1.6 -3.9 T
3 0.2 -9.4 T
4 -1.3 1.5 U
5 -0.4 -1.3 T
6 -3.5 -9.4 T
7 2.2 3.4 U
8 0.7 -2.6 T
9 -2.5 -3.3 T
10 0.4 -4.1 T
11 -3.9 -3.7 U
12 0.2 -0.2 T
13 0.8 -2.0 T
14 0.7 -1.0 T
15 -0.7 -3.3 T
AVERAGE -1.1 -2.9
5 Note: The higher the "L" value, the lighter the skin.
TABLE 4
Chan a from Baseline in "a" Vaiue 4 Da s Post Bruising
Subject # Treated Arm Untreated Which Better
Arm
1 3.5 3.3 U
2 1.0 3.3 T
3 -0.2 5.9 T
4 -0.3 -0.9 U
5 1.0 0.3 U
6 -1.3 5.2 T
7 -2.0 -2.8 U
8 0.3 2.7 T
9 1.0 0.9 U
10 -0.2 2.4 T
11 1.5 4.6 T
12 -0.7 0.2 T
13 0.2 2.2 T
14 -0.8 1.3 T
15 0.9 1.7 T
AVERAGE 0.26 2.02
Note: A higher "a" value indicates skin is redder.
17
CA 02309179 2000-OS-04
WO 00/13661 PCT/US99/20854 ,
TABLE 5 --
Change from Baseline in "b" Value 4 Days Post Bruising
Subject # Treated Untreated Which Better
Arm Arm
~
1 5.9 6.5 T
2 1.9 3.9 T
3 0.4 5.2 T
4 2.6 2.9 T
0.1 0.0 U
6 5.5 3.9 U
7 -0.3 -1.8 U
8 0.4 3.6 T
9 0.4 2.5 T
2.4 5.6 T
11 6.8 0.6 U
12 1.0 2.0 T
13 -0.8 1.1 T
14 -1.3 2.7 T
0.5 3.1 T
AVERAGE 1.7 2.8
Note: Higher "b" value indicates skin is more yellow.
5
The data clearly suggest that daily use of a product, such as
Sample A, can help reduce the susceptibility to bruising. Bruising may still
occur, but bruises may be less severe.
10 Various modifications and alterations to the present invention may
be appreciated based on a review of this application. These changes and
additions are intended to be within the scope and the spirit of the present
invention as defined by the following claims.
18
