U.S. patent application number 16/626248 was filed with the patent office on 2022-02-03 for formulations for hair growth.
The applicant listed for this patent is JENIVISION INC.. Invention is credited to Weizhen WANG, David F. WOODWARD.
Application Number | 20220031638 16/626248 |
Document ID | / |
Family ID | 1000006090815 |
Filed Date | 2022-02-03 |
United States Patent
Application |
20220031638 |
Kind Code |
A9 |
WANG; Weizhen ; et
al. |
February 3, 2022 |
FORMULATIONS FOR HAIR GROWTH
Abstract
The present invention is directed to compositions and
formulations for hair growth. The non-aqueous, preservative-free
formulations are useful for the growth of hair, eyebrows and
eyelash in a variety of setting. Also provided herein are
non-aqueous, preservative-free formulations and methods for the
treatment of dry-eye and related symptoms.
Inventors: |
WANG; Weizhen; (Irvine,
CA) ; WOODWARD; David F.; (Lake Forest, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
JENIVISION INC. |
Irvine |
CA |
US |
|
|
Prior
Publication: |
|
Document Identifier |
Publication Date |
|
US 20200215007 A1 |
July 9, 2020 |
|
|
Family ID: |
1000006090815 |
Appl. No.: |
16/626248 |
Filed: |
June 30, 2017 |
PCT Filed: |
June 30, 2017 |
PCT NO: |
PCT/US17/40453 PCKC 00 |
371 Date: |
December 23, 2019 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 47/44 20130101;
A61K 47/10 20130101; A61P 17/14 20180101; A61K 31/16 20130101; A61K
9/0014 20130101 |
International
Class: |
A61K 31/16 20060101
A61K031/16; A61K 47/44 20060101 A61K047/44; A61K 47/10 20060101
A61K047/10; A61P 17/14 20060101 A61P017/14; A61K 9/00 20060101
A61K009/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 5, 2016 |
CN |
201610525215.4 |
Claims
1. A formulation for the stimulation of hair growth wherein the
formulation is comprised of: at least one eicosanoid; at least one
oil; and at least one alcohol; wherein the formulation is
substantially free of water; and the formulation is substantially
free of preservatives.
2. A formulation for use in treating a condition selected from the
group consisting of hypotrichosis of the eyelashes, hair loss of
the eyebrows, hair loss of the scalp, and hypotrichosis associated
with chemotherapy treatment regimens, wherein the formulation is
comprised of: bimatoprost; at least one oil; and at least one
alcohol; wherein the formulation is substantially free of water;
and the formulation is substantially free of preservatives.
3. A formulation for use in treating a condition selected from the
group consisting of hypotrichosis of the eyelashes, hair loss of
the eyebrows, hair loss of the scalp, and hypotrichosis associated
with chemotherapy treatment regimens, wherein the formulation is
comprised of bimatoprost and an optionally substituted
C.sub.7-C.sub.20 alkanol.
4. A formulation comprising bimatoprost, an oil, and an alcohol,
for use in: i) treating a condition selected from the group
consisting of hypotrichosis of the eyelashes, hair loss of the
eyebrows or hair loss of the scalp; ii) regenerating hair on the
face, scalp or body; iii) modifying at least one hair in length,
base circumference, rigidity, or color; iv) increasing the number
of hairs per area of skin; or v) converting villous hair to
terminal hair.
5. A formulation for use in treating a condition selected from the
group consisting of hypotrichosis of the eyelashes, hair loss of
the eyebrows, hair loss of the scalp, and hypotrichosis associated
with chemotherapy treatment regimens, wherein the formulation
consists essentially of: bimatoprost; at least one oil; and at
least one alcohol; wherein the formulation is substantially free of
water; and the formulation is substantially free of
preservatives.
6. A method for use in treating a condition selected from the group
consisting of hypotrichosis of the eyelashes, hair loss of the
eyebrows, hair loss of the scalp, and hypotrichosis associated with
chemotherapy treatment regimens, comprising administrating to the
patient a formulation comprised of: at least one eicosanoid; at
least one oil; and at least one alcohol; wherein the formulation is
substantially free of water; and the formulation is substantially
free of preservatives.
7. A method for use in treating a condition selected from the group
consisting of hypotrichosis of the eyelashes, hair loss of the
eyebrows, hair loss of the scalp, and hypotrichosis associated with
chemotherapy treatment regimens, comprising administrating to the
patient a formulation comprised of: bimatoprost; at least one oil;
and at least one alcohol; wherein the formulation is substantially
free of water; and the formulation is substantially free of
preservatives.
8. A method for use in treating a condition selected from the group
consisting of hypotrichosis of the eyelashes, hair loss of the
eyebrows, hair loss of the scalp, and hypotrichosis associated with
chemotherapy treatment regimens, comprising administrating to the
patient a formulation consisting essentially of: bimatoprost; at
least one oil; and at least one alcohol; wherein the formulation is
substantially free of water; and the formulation is substantially
free of preservatives.
9. A method of relieving dry eye by applying a formulation
comprising at least one naturally occurring oil to the eyelid
margin, wherein the formulation is substantially free of water and
is free of preservatives.
10. A method of application whereby the formulation of any of
claims 1-205 is delivered to the eyelid margin by a positive
displacement device comprising a reservoir attached to a roller
ball, brush, or felt tip device.
11. A non-aqueous, non-preserved formulation for stimulating hair
growth, comprising an eicosanoid, ethanol and an oil, wherein the
eicosanoid is present in a concentration of about 0.01%-0.3% w/v
and ethanol is present in a concentration of about 1%-7% v/v.
Description
FIELD OF THE INVENTION
[0001] The present invention is directed generally to compositions
and formulations for hair growth. The present invention is directed
specifically to non-aqueous hair, eyebrows and eyelash growth
formulations of active eicosanoids which do not contain
preservatives.
SUMMARY OF THE INVENTION
[0002] Non-aqueous formulations and methods for formulating hair
growth promoting eicosanoids are described such that the chemical
stability of eicosanoids and their pro-drugs is improved and the
use of preservatives is not necessary in the formulation. Although
it is optional, a bulk packing hair growth product may contain
preservatives to prolong the shelf life once opened for daily use.
Such non-aqueous formulations are composed of ingredients that
occur naturally. These formulations may be delivered by methods and
devices that conserve usage and are convenient to the patient. Of
notable utility is a positive displacement cylindrical device
fitted with a felt/fiber tip or a specialized brush for direct
application to the eyelid margin. Such a delivery method results in
reduced risk of applying drug to unwanted areas such as the eyeball
and conjunctiva. Further, the addition of natural hair shaft and
hair follicle health promoting and appearance enhancing essential
and plant oils are included in the formulations.
[0003] One aspect of the present invention includes a method for
treating alopecia or hair loss and/or an attribute associated with
hair loss, such as hair thinning, hair color loss, no new hair
shaft growth, reduced rate of hair shaft growth, reduced hair shaft
diameter (thickness), reduced hair shaft length, reduced hair
density, reduced hair pigmentation, reduced melanin production,
decreased keratinization of the hair shaft, reduced hair shaft
luster, reduced hair health, increased fragility of the hair shaft,
reduced time a hair follicle spends in anagen phase, reduced time a
hair follicle spends in catagen phase, reduced time a hair follicle
spends in telogen phase, premature release of hair shaft from hair
follicle in exogen phase, premature initiation of apoptosis in hair
follicle, premature conversion of a terminal hair into a vellus
hair, failure of vellus hair to convert to terminal hair.
INCORPORATION BY REFERENCE
[0004] All publications, patents, and patent applications mentioned
in this specification are herein incorporated by reference to the
same extent as if each individual publication, patent, or patent
application was specifically and individually indicated to be
incorporated by reference.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] The novel features of the invention are set forth with
particularity in the appended claims. A better understanding of the
features and advantages of the present invention will be obtained
by reference to the following detailed description that sets forth
illustrative embodiments, in which the principles of the invention
are utilized, and the accompanying drawings of which:
[0006] FIG. 1 shows one embodiment of an applicator device;
[0007] FIG. 2 shows the results of no bacterial and fungal growth
on Formulation 3, Table 1 as described in Example I.
[0008] FIG. 3 shows the results of the growth of right eyelash and
left and right eyebrows using Formulation 13, Table 2 as described
in Example III.
[0009] FIG. 4 shows the results of the growth of right eyelash
using Formulation 13, Table 2 as described in Example IV.
DETAILED DESCRIPTION OF THE INVENTION
Terms and Definitions
[0010] The terms "about", "approximate" and "approximately" are
used herein to modify a numerical value and indicate a defined
range around that value. If "x" were the value, "about x" or
"approximately equal to x" would generally indicate a value from
0.90x to 1.10x. Any reference to "about x" minimally indicates at
least the values x, 0.90x, 0.91x, 0.92x, 0.93x, 0.94x, 0.95x,
0.96x, 0.97x, 0.98x, 0.99x, 1.01x, 1.02x, 1.03x, 1.04x, 1.05x,
1.06x, 1.07x, 1.08x, 1.09x, and 1.10x. Thus, "about x" is intended
to disclose, e.g., "0.98x." When "about" is applied to the
beginning of a numerical range, it applies to both ends of the
range. Thus, "from about 6 to 8.5" is equivalent to "from about 6
to about 8.5." When "about" is applied to the first value of a set
of values, it applies to all values in that set. Thus, "about 7, 9,
or 11%" is equivalent to "about 7%, about 9%, or about 11%." About
may also refer to a number close to the cited number that would
result in a bioequivalent therapeutic effect by a regulatory agency
such as the FDA or the EMEA.
[0011] The term "alcohol" refers to an alkyl substituted with at
least one hydroxy substituent. The alkyl can be substituted with
one, two, three, four, five, or six hydroxy substituents. In
certain embodiments, an alcohol comprises one to fifteen carbon
atoms (e.g., C.sub.1-C.sub.15 alcohol). In certain embodiments, an
alcohol comprises one to ten carbon atoms (e.g., C.sub.1-C.sub.10
alcohol). In certain embodiments, an alcohol comprises one to eight
carbon atoms (e.g., C.sub.1-C.sub.8 alcohol). In certain
embodiments, an alcohol comprises one to six carbon atoms (e.g.,
C.sub.1-C.sub.6 alcohol). In certain embodiments, an alcohol
comprises one to three carbon atoms (e.g., C.sub.1-C.sub.3
alcohol).
[0012] The term "Alkyl" refers to a straight or branched
hydrocarbon chain radical consisting solely of carbon and hydrogen
atoms, optionally containing unsaturation, having from one to
twenty six carbon atoms (e.g., C.sub.1-C.sub.26 alkyl)). In certain
embodiments, an alkyl comprises one to twenty four carbon atoms
(e.g., C.sub.1-C.sub.24 alkyl). In certain embodiments, an alkyl
comprises one to twenty two carbon atoms (e.g., C.sub.1-C.sub.22
alkyl). In certain embodiments, an alkyl comprises one to twenty
carbon atoms (e.g., C.sub.1-C.sub.20 alkyl). In certain
embodiments, an alkyl comprises one to eighteen carbon atoms (e.g.,
C.sub.1-C.sub.18 alkyl). In certain embodiments, an alkyl comprises
one to sixteen carbon atoms (e.g., C.sub.1-C.sub.16 alkyl). In
certain embodiments, an alkyl comprises one to ten carbon atoms
(e.g., C.sub.1-C.sub.10 alkyl). In certain embodiments, an alkyl
comprises one to eight carbon atoms (e.g., C.sub.1-C.sub.8 alkyl).
In other embodiments, an alkyl comprises one to five carbon atoms
(e.g., C.sub.1-C.sub.5 alkyl). In other embodiments, an alkyl
comprises one to four carbon atoms (e.g., C.sub.1-C.sub.4 alkyl).
In other embodiments, an alkyl comprises one to three carbon atoms
(e.g., C.sub.1-C.sub.3 alkyl). In other embodiments, an alkyl
comprises one to two carbon atoms (e.g., C.sub.1-C.sub.2 alkyl). In
other embodiments, an alkyl comprises one carbon atom (e.g.,
C.sub.1 alkyl). In other embodiments, an alkyl comprises five to
fifteen carbon atoms (e.g., C.sub.5-C.sub.15 alkyl). In other
embodiments, an alkyl comprises five to eight carbon atoms (e.g.,
C.sub.5-C.sub.8 alkyl). In other embodiments, an alkyl comprises
two to five carbon atoms (e.g., C.sub.2-C.sub.5 alkyl). In other
embodiments, an alkyl comprises three to five carbon atoms (e.g.,
C.sub.3-C.sub.5 alkyl). In other embodiments, the alkyl group is
selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl
(iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl),
2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl),
1-pentyl (n-pentyl).
[0013] In some embodiments the alcohol is a C.sub.5-20 alkanol. In
some embodiments the alcohol is a C.sub.5-20 alkanol is a diol. In
some embodiments the alcohol is a C.sub.5-20 alkanol is a triol. In
some embodiments the alcohol is a C.sub.5-20 alkanol wherein the
alkane portion of the alkanol is branched. In some embodiments the
C.sub.5-20 alkanol is saturated. In some embodiments the C.sub.5-20
alkanol is unsaturated.
[0014] "Alopecia" is defined as hair loss and includes
hypotrichosis of the eyelashes or loss of hair from eyebrows and
may include different types of alopecia including but not limited
to alopecia areata, scarring alopecia, non-scarring alopecia,
androgenetic alopecia, telogen effluvium, trichotillomania,
alopecia universalis, androgenic alopecia and alopecia totalis,
transient alopecia areata, diffuse pattern alopecia.
[0015] The term "eicosanoid" refers to a signaling molecule made by
the oxidation of arachidonic acid or other polyunsaturated fatty
acids. Eicosanoids are 20 carbon units in length. Examples of
eicosanoids include prostanoids, leukotrienes, lipoxins, resolvins,
and eoxins.
[0016] The term "prostanoid" refers to physiologically active lipid
compounds derived from fatty acids. Many prostanoids act as
vasodilators and inhibit the aggregation of blood platelets.
Examples of prostanoids include prostaglandin F.sub.2.alpha.,
dinoprost, latanoprost, bimatoprost, travoprost, carboprost,
tafluprost, and thromboxane.
[0017] The term "prostamide" refers to physiologically active
lipids derived from fatty acid amides, notably anandamide. These
are known to lower intraocular pressure, reduce fat deposits, and
increase hair growth. Examples include bimatoprost, and prostamides
F.sub.2.alpha., E.sub.2, and D.sub.2.
[0018] The term "leukotriene" refers a family of eicosanoid
inflammatory mediators produced in leukocytes by the oxidation of
arachidonic acid and the essential fatty acid eicosapentaenoic
acid. Examples of leukotriene include leukotriene C.sub.4,
leukotriene D.sub.4, leukotriene E.sub.4, leukotriene F.sub.4,
leukotriene B.sub.4, leukotriene G4, and leukotriene B5.
[0019] The term "lipoxin" refers to bioactive autacoid metabolites
of arachidonic acid. Lipoxins often play important roles in
inflammatory responses. Examples of lipoxins include lipoxin
lipoxin B.sub.4, 15-epi-lipoxin A.sub.4, and 15-epi-lipoxin B4.
[0020] The term "resolvin" refers to autacoid metabolites of
arachidonic acid. Many resolvins have been seen to possess
anti-inflammation, tissue protection, and tissue healing
activities. Examples of resolvins include resolvin Ds, resolvin Es,
resolvin Dn-6DPA, and resolvin Dn-3DPA.
[0021] The term "eoxin" refers to a family of proinflammatory that
are produced in human eosinophils and mast cells through the
metabolism of arachidonic acid. Many eoxins contribute to
inflammation in airway allergies and certain types of cancers.
Examples of eoxins include eoxin A.sub.4, eoxin C.sub.4, eoxin
D.sub.4, and eoxin E.sub.4.
[0022] The term "glyceride" refer to esters formed from glycerol
and at least one fatty acid. The term glyceride is meant to include
monoglycerides, diglycerides and triglycerides. Many vegetable and
animal oils contain triglycerides.
[0023] The term "preservative" refers to a chemical that prevents,
slows or inhibits the decomposition of a formulation. In some
instances, a preservative prevents decomposition of the active
ingredient by preventing, slowing or inhibiting decomposition by
microbial or chemical interaction. Non-limiting examples of a
preservative include benzalkonium chloride (BAK), purite,
benzododecinium bromide, ionic buffered systems, polixetonium,
sodium perborate, polyhexamethylene biguanide, polyquad, GenAqua,
and sofZia. The term preservatives is also meant to encompass
stabilizers such as perborate, boric acid and
ethylenediaminetetraacetic acid (EDTA).
[0024] "Hypotrichosis" is a condition of abnormal hair loss or
reduction.
[0025] "Non-aqueous formulations" are formulations that contain no
water.
[0026] "Plant oils" refer to oils derived from plant sources. There
are three primary types of plant oil, differing both the means of
extracting the relevant parts of the plant, and in the nature of
the resulting oil: (1) Vegetable oils historically extracted by
putting part of the plant under pressure, squeezing out the oil;
(2) Macerated oils consisting of a base oil to which parts of
plants are added; and, (3) Essential oils composed of volatile
aromatic compounds, extracted from plants by distillation.
[0027] The term "oil" as used in the formulations described herein
refers to a liquid or semi-solid hydrophobic substance derived from
a plant, animal or petrochemical source.
[0028] In some embodiments, the oil may be derived from almond,
argan, avocado, beech nut, blackcurrant seed, brazil nut, butternut
squash seed, camellia (tea seed), cape chestnut, cashew nut,
castor, cocoa butter, coconut, corn, cottonseed, flaxseed, grape
seed, hazelnut, hemp seed, jojoba, kapok seed, kenaf seed, okra
seed, olive, palm, peanut, pomegranate seed, poppy seed, soybean,
sunflower seed or any combinations thereof.
[0029] In some embodiments, the oil may be derived from angelica
root, balsam of Peru, basil, camphor, cannabis flower, cardamom,
carrot seed, cedarwood, chamomile, calamus, cinnamon, cistus,
citron, citronella, clary sage, clove, coriander, costus root,
cranberry seed, cumin, cypress, davana, elecampane, eucalyptus,
fennel seed, frankincense, galangal, galbanum, geranium, goldenrod,
grapefruit seed, henna, helichrysum, hickory nut, Idaho tansy,
jasmine, juniper berry, Laurus nobilis, lavender, ledum,
lemongrass, mandarin, menthe arvensis, moringa, mountain savory,
mugwort, myrrh, neroli, nutmeg, parsley, patchouli, perilla,
pennyroyal, petitgrain, red cedar, rose, rosehip, rosemary,
rosewood, sage, sassafras, schisandra, spikenard, spruce, star
anise, tea tree, thyme, tumanu, tonka bean, vetiver, western red
cedar, wintergreen, yarrow, ylang-ylang.
[0030] In some embodiments, a plant oil is a vegetable oil, an
essential oil, a herbal supplement oil, or any combinations
thereof.
[0031] In some embodiments, a plant is coconut oil, corn oil,
cottonseed oil, olive oil, palm oil, peanut oil, rapeseed oil,
canola oil, safflower oil, sesame oil, soybean oil, sunflower oil,
almond oil, beech nut oil, brazil nut oil, cashew oil, hazelnut
oil, macadamia oil, mongongo nut oil, pecan oil, pine nut oil,
pistachio oil, walnut oil, grapefruit seed oil, lemon oil, orange
oil, bitter gourd oil, buffalo gourd oil, butternut squash seed
oil, pumpkin seed oil, watermelon seed oil, acai oil, black seed
oil, blackcurrant seed oil, borage seed oil, flaxseed oil, amaranth
oil, apricot oil, apple seed oil, argan oil, avocado oil, babassu
oil, ben oil, borneo tallow nut oil, carob pod oil (algaroba oil),
cocoa butter sometimes known as theobroma oil, cocklebur oil,
sunflower oil, cohune oil, coriander seed oil, date seed oil, dika
oil, false flax oil, grape seed oil, hemp oil, kapok seed oil,
kenaf seed oil, cottonseed oil, lallemantia oil, mafura oil, marula
oil, meadowfoam seed oil, mustard oil, niger seed oil, nutmeg oil,
okra seed oil, perilla seed oil, persimmon seed oil, pequi oil,
pili nut oil, pomegranate seed oil, poppy seed oil, pracaxi oil,
prune kernel oil, quinoa oil, ramtil oil, rice bran oil, royle oil,
sacha inchi oil, sapote oil, seje oil, shea oil, taramira oil, tea
seed oil, tigernut oil (or nut-sedge oil), tobacco seed oil, tomato
seed oil, wheat germ oil, agar oil, ajwain oil, angelica root oil,
anise oil, asafoetida oil, basil oil, bay oil, bergamot oil, black
pepper oil, buchu oil, birch oil, camphor oil, cannabis flower
essential oil, calamodin oil, calamansi essential oil, caraway oil,
cardamom seed oil, carrot seed oil, cedar oil (or cedarwood oil),
chamomile oil, calamus oil, cinnamon oil, citron oil, citronella
oil, clary sage oil, coconut oil, coffee oil, coriander oil,
costmary oil (bible leaf oil), costus root oil, cranberry seed oil,
cubeb oil, cumin oil, cypress oil, cypriol oil, curry leaf oil,
davana oil, elecampane oil, elemi oil, eucalyptus oil, fennel seed
oil, fenugreek oil, fir oil, frankincense oil, galangal oil,
galbanum oil, geranium oil, ginger oil, goldenrod oil, helichrysum
oil, hickory nut oil, horseradish oil, jasmine oil, juniper berry
oil, lavender oil, melaleuca see tea tree oil, melissa oil, mint
oil, moringa oil, mugwort oil, myrrh oil, myrtle neem oil or neem
tree oil, oregano oil, orris oil, parsley oil, patchouli oil,
perilla essential oil, pennyroyal oil, peppermint oil, pine oil,
rose oil, rosehip oil, rosemary oil, rosewood oil, sage oil,
sassafras oil, savory oil, schisandra oil, spearmint oil, spruce
oil, star anise oil, tarragon oil, tea tree oil, thyme oil, vetiver
oil (khus oil), yarrow oil or any combinations thereof.
[0032] In some embodiments, an animal oil is bone oil, cod liver
oil, fish oil, goose grease, halibut-liver oil, lard oil, menhaden
oil, neat's-foot oil, oleo oil, salmon oil, sardine oil, shark oil,
wool oil or tallow oil.
[0033] In some embodiments, a petrochemical derived oil is mineral
oil, silicone oil, petroleum, and mixtures of C.sub.9-20
alkanes.
[0034] In some embodiments, the oil is a vitamin oil. Examples of
vitamin oils include vitamin A oil, vitamin D oil, vitamin E oil,
and vitamin K oil. Additional examples include oils containing
retinol, retinal, carotenoid, carotene, cholecalciferol,
ergocalciferol, tocopherol, tocotrienol, phylloquinone, and
menaquinone.
[0035] In some embodiments, an oil is a glyceride or contains a
glyceride. Examples of glycerides that can act as oils or can in
oils include glycerides derived from at least one molecule of
propanoic acid, butanoic acid, pentanoic acid, hexanoic acid,
heptanoic acid, octanoic acid, nonanoic acid, decanoic acid,
undecanoic acid, dodecanoic acid, tridecanoic acid, tetradecanoic
acid, pentadecanoic acid, hexadecanoic acid, heptadecanoic acid,
octadecanoic acid, nonadecanoic acid, eicosanoic acid,
heneicosanoic acid, docosanoic acid, tricosanoic acid,
tetracosanoic acid, pentacosanoic acid, hexacosanoic acid, crotonic
acid, myristoleic acid, palmitoleic acid, sapienic acid, oleic
acid, elaidic acid, vaccenic acid, erucic acid, nervonic acid,
linoleic acid, eicosadienoic acid, docosadienoic acid, linolenic
acid, pinolenic acid, eleostearic acid, .beta.-eleostearic acid,
mead acid, dihomo-.gamma.-linolenic acid, eicosatrienoic acid,
stearidonic acid, arachidonic acid, eicosatetraenoic acid, adrenic
acid, bosseopentaenoic acid, eicosapentaenoic acid, ozubondo acid,
sardine acid, tetracosanolpentaenoic acid, docosahexaenoic acid,
herring acid, stearidonic acid, eicosapentaenoic acid,
docosatetraenoic acid, paullinic acid, palmitoleic acid, gondoic
acid, and erucic acid.
[0036] In some embodiments, an oil is a fatty acid. Examples of
fatty acids that can act as oils include propanoic acid, butanoic
acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid,
nonanoic acid, decanoic acid, undecanoic acid, and dodecanoic acid.
In some embodiments, the fatty acid is a C8-C16 fatty acid. In some
embodiments, the fatty acid is a C12-C26 fatty acid.
[0037] In some embodiments, an oil is a phospholipid, sphingolipid,
glycolipid, cholesterol, or saccharolipids.
[0038] "Preservative free multi-use applicator" refers to an
applicator that can provide multiple single doses of a
non-preserved formulation.
[0039] "Prevent", "preventing" or "prevention" can refer to
stopping any disease, condition or symptoms or reducing symptoms in
a clinically significant manner, particularly as compared to
patients receiving no treatment at all.
[0040] "Prostanoids" are a subclass of eicosanoids such as
prostaglandins, prostacyclin, thromboxanes and prostamides.
[0041] "Treatment", "treat" or "treating" refers to curing any
disease or condition or reducing or alleviating the symptoms of the
disease or condition.
Hair Growth
[0042] Prostanoids and prostamides have proven useful for
increasing hair growth. In addition to restoring eyelashes and
eyebrows in persons on chemotherapy, prostanoids have gained
popularity and commercial success for eyelash growth. The effect of
latanoprost, bimatoprost, travoprost and pharmacologically related
entities on eyelashes was originally discovered during clinical
trials on glaucoma patients. U.S. Pat. No. 6,626,105 teaches that
prostanoids and their derivatives provide useful compounds for
promoting eyelash growth. It was further reported that bimatoprost
produces eyelash growth in humans. A number of reports were issued
and patents filed thereafter on the prostanoids and eyelash and
other hair growth, for example, U.S. Pat. No. 8,227,514. For
bimatoprost specifically, the mechanism of action for increased
eyelash growth has been proven to involve increased entry into
anagen and extension of the anagen growth phase (Br J Dermatol.
2010 June; 162(6):1186-97; Characterization of an in vivo model for
the study of eyelash biology and trichomegaly: mouse eyelash
morphology, development, growth cycle, and anagen prolongation by
bimatoprost. Tauchi M, Fuchs T A, Kellenberger A J, Woodward D F,
Paus R, Liitjen-Drecoll E). A similar mechanism of action has been
reported for isolated human scalp hair follicles (FASEB J. 2013
February; 27(2):557-67). The prostamide-related glaucoma therapy,
bimatoprost, offers one approach for treating scalp alopecias.
Khidhir K G, Woodward D F, Farjo N P, Farjo B K, Tang E S, Wang J
W, Picksley S M, Randall V A).
[0043] Typically, the prostanoids are formulated in aqueous
solutions, dripped onto a brush, and then brushed onto the base of
the eyelashes. This is the case for the FDA approved eyelash growth
product Latisse.RTM.. However, aqueous solutions accelerate
chemical instability of the eicosanoids and their prodrugs. For
example, the prostanoid FP receptor agonist prodrug latanoprost, as
the active product ingredient in Xalatan.RTM., undergoes facile
hydrolysis in aqueous solution and is stored refrigerated to retard
such facile de-esterification. Eyelash growth products are
typically formulated similar to eye drop products, in aqueous
solution and containing a preservative such as shown in US
20080275118, EP 2498783, WO 2012038469, WO 2014158373, and US
20150025097. The use of a non-aqueous formulation such as those
described above prevents de-esterification of the ester moiety of
prostanoid prodrugs. These prodrugs may be alkyl esters
(Stjernschantz et al., 1992; U.S. Pat. Nos. 5,510,383, 8,865,766)
or phosphate esters (WO 2014070784). Prostanoids with a
cyclopentenone ring in the structure are also prone to dehydration
and elimination of the H.sub.2O moiety from the ring, and this
process may be accelerated in aqueous formulations. Moreover, the
brushes supplied in kit form are disposable and are for single use
of one eye only (Latisse.RTM., see product use instructions). There
is unavoidable waste in this procedure and is costly in terms of
raw materials. For example, bimatoprost costs about one million two
hundred thousand U.S. dollars per kilogram and is therefore very
expensive to use in a hair-growth formulation. Further, the brush
must be soaked in aqueous formulation and much of this cannot be
transposed onto the eyelid and is inextricably held within the
brush. Moreover, the aqueous solutions sometimes drop off the
brush.
[0044] Preservatives are often regarded as an unwanted necessity,
preserving the formulation but with deleterious effects on the eye.
One common solution to the problem of preservation is to dispense
the product in a unit dose form. However, unit dose packaging is
significantly more expensive than multi-dose packaging, adding to
the cost of the final product. For example, with the product
Latisse.RTM., a preserved solution is supplied with single-use,
disposable brush applicators. This greatly adds to the cost of the
final product. When eicosanoids are formulated in a non-aqueous
formulation, the need for a preservative is removed. This permits
the use of multiple dose delivery from a single applicator, which
is easier for carrying and travel around.
Dry Eye Disease
[0045] Dry eye has many root causes and these diverse etiological
origins translates into an estimated 5-35% of affected persons
worldwide. The full impact of "dry eye" may not be felt for a
couple of decades until the contributions of environmental and,
increasingly, situational factors and the exacerbations associated
with an aging population are made manifest. Environmental factors
include gaseous pollution, dust, dry air, wind, and heat.
Situational factors are largely related to TV, computer, and
cellphone screens. The drastically reduced blinking rate caused by
watching at computer screens results in "dry eye" due to a lack of
irrigation of the ocular surface. Dry eye disease is a separate
entity, although the symptomology may be similar. Dry eye disease
is a diagnosed inflammatory/autoimmune disease that affects the
lacrimal gland and reduces tear secretion. Dry eye of all origins,
if allowed to continue without remedial intervention, could
eventually worsen to the point where effects on the cornea
compromise daily life; driving, working (M Meadows, FDA Consumer
Magazine, May-June, 2005; Nichols K K, et al. Invest Ophthalmol Vis
Sci 57; 2975-2982, 2016).
[0046] Tears moisten and lubricate the cornea and are composed of
aqueous, mucus, and highly complex lipid components (Butovich I A
et al. Biochim Biophys Acta 1861; 538-553, 2016; Chen J et al.
Invest Ophthalmol Vis Sci 58; 2266-2274, 2017). The aqueous film
provided by the tears is of modest benefit in itself, the watery
tears associated with irritation or emotion give little or no
relief from dry eye. Lack of lubrication is considered important in
the development of "dry eye" (Knop E et al. Invest Ophthalmol Vis
Sci 52; 1938-1978, 2011). The Meibomian gland secretion, meibum, is
composed of numerous lipid species rendering it difficult to
directly replace.
[0047] Apart from immunologically-based dry eye disease, dry eye is
treated with lubricating aqueous solutions, purported to be
artificial tears. The lubrication ingredient is typically man-made
and not a naturally occurring substance. These lubricants include
hydroxypropylmethyl cellulose, carboxymethyl cellulose, polyvinyl
alcohol, glycerin, hyaluronic acid, polysorbate, propylene glycol,
and polyethylene glycol. Tear replacements include preservatives.
The safety profiles of the preservatives vary but damage to the
corneal epithelium occurs at all high doses and it is recommended
that administration of such artificial tears should be limited to 4
to 6 times a day (Moshirfar M et al. Clin Ophthalmol 8: 1419-1433,
2014).
Compositions and Methods of Use
Hair Growth
[0048] Some embodiments of the present invention include: [0049] A)
A non-aqueous, non-preserved formulation for use in treating one
selected from the group consisting of the eyelashes, hair loss of
the eyebrows or hair loss of the scalp, comprised of bimatoprost,
ethanol, and at least one plant oil, such as jojoba oil, castor
oil, avocado oil, olive oil, sweet almond oil and optionally at
least one essential oil. [0050] B) The non-aqueous, non-preserved
formulation of embodiment A wherein the formulation is for
treatment of hypotrichosis of the eyelashes and the bimatoprost is
present in a concentration of 0.01%-0.03% w/v. [0051] C) The
non-aqueous, non-preserved formulation of embodiment B wherein the
formulation is applied to at least one eyelid margin for treatment
of hypotrichosis of the eyelashes. [0052] D) The non-aqueous,
non-preserved formulation of embodiment C wherein the formulation
is applied to the upper eyelid margin. [0053] E) The non-aqueous,
non-preserved formulation of embodiment D wherein the formulation
is applied once a day. [0054] F) The non-aqueous, non-preserved
formulation of embodiment E wherein the formulation comprises
ethanol, castor oil and jojoba oil. [0055] G) The non-aqueous,
non-preserved formulation of embodiment F wherein the formulation
further comprises one oil selected from the group consisting of
avocado oil, olive oil and sweet almond oil. [0056] H) The
non-aqueous, non-preserved formulation of embodiment G wherein the
formulation further comprises one oil selected from the group
consisting of castor oil, avocado oil, jojoba oil, olive oil, sweet
almond oil, vitamin E. [0057] I) The non-aqueous, non-preserved
formulation of embodiment A comprising bimatoprost, absolute
ethanol, castor oil and jojoba oil. [0058] J) The non-aqueous,
non-preserved formulation of embodiment I comprising about 0.03%
w/v bimatoprost, about 1% v/v ethanol, about 3% v/v castor oil and
about 96% v/v jojoba oil. [0059] K) The formulation of embodiment B
wherein the formulation is applied to the eyelid margins by a
multi-use applicator. [0060] L) The formulation of embodiment B
comprising 0.02%-0.03% w/v bimatoprost, about 1% v/v ethanol, about
3% v/v castor oil, and about 70-96% v/v jojoba oil. [0061] M) The
formulation of embodiment L comprising 0.02% w/v bimatoprost.
[0062] N) The formulation of embodiment M wherein the formulation
applied once a day to the eyelid margins avoids ocular side effects
to a greater degree as compared to a 0.03% w/v bimatoprost solution
applied once a day to the eyelid margins. [0063] O) The formulation
of embodiment M wherein application of the formulation results in
more bimatoprost delivered to the eyelid margin by a single
application than a 0.03% w/v solution of bimatoprost. [0064] P) The
formulation of embodiment M wherein the formulation results in
equal or greater eyelash growth than a 0.03% w/v solution of
bimatoprost. [0065] Q) The formulation of embodiment B wherein the
once daily application of the formulation to a patient results in
eyelashes that are longer, denser and darker than a patient not
applying the formulation. [0066] R) The formulation of embodiment B
wherein the formulation applied to the upper eyelid once a day
results in longer eyelashes within 60 days. [0067] S) The
formulation of embodiment A wherein the formulation is applied to
one selected from the group consisting of upper eyelid margin,
eyebrows and the scalp. [0068] T) The formulation of embodiment S
wherein the formulation results in increased hair growth of at
least one selected from the group consisting of eyelashes, eyebrows
and scalp hair. [0069] U) A formulation for eyelash or eyebrow
growth selected from any formulation of Tables I-IV. [0070] V) A
formulation for scalp hair growth or eyebrow hair growth selected
from any formulations of Tables I-IV. [0071] W) The formulation of
embodiment V wherein the formulation is applied to the eyebrows or
scalp once a day. [0072] X) The formulation of embodiment V wherein
the formulation is applied to the eyebrows or scalp twice a day.
[0073] Y) The formulation of embodiment W wherein once daily
application causes increased scalp hair or eyebrow growth. [0074]
Z) Use of one selected from the group consisting of bimatoprost,
latanoprost, tafluprost and travoprost for increasing one selected
from the group consisting of eyelash growth, eyebrow growth or
scalp hair growth. [0075] AA) A prostanoid and a natural oil to aid
activity, improve hair appearance, provide hair follicle
nourishment, improve hair shaft curl, or aid solubility selected
from the group consisting of angelica root, balsam of Peru, basil,
camphor, cannabis flower, cardamom, carrot seed, cedarwood,
chamomile, calamus, cinnamon, cistus, citron, citronella, clary
sage, clove, coriander, costus root, cranberry seed, cumin,
cypress, davana, elecampane, eucalyptus, fennel seedfrankincense,
galangal, galbanum, geranium, goldenrod, grapefruit seed, henna,
helichrysum, hickory nut, Idaho tansy, jasmine, juniper berry,
Laurus nobilis, lavender, ledum, lemongrass, mandarin, menthe
arvensis, moringa, mountain savory, mugwort, myrrh, neroli, nutmeg,
parsley, patchouli, perilla, pennyroyal, petitgrain, red cedar,
rose, rosehip, rosemary, rosewood, sage, sassafras, schisandra,
spikenard, spruce, star anise, tea tree, thyme, tumanu, tonka bean,
vetiver, western red cedar, wintergreen, yarrow, ylang-ylang.
Triglycerides extracted from plants and their seeds are also
contemplated as useful as a solvent, medicinal, and/or cosmetic
properties that may be selected from the following oils: almond,
argan, avocado, beech nut, blackcurrant seed, brazil nut, butternut
squash seed, camellia (tea seed), cape chestnut, cashew nut,
castor, cocoa butter, coconut, corn, cottonseed, flaxseed, grape
seed, hazelnut, hemp seed, jojoba, kapok seed, kenaf seed, okra
seed, olive, palm, peanut, pomegranate seed, poppyseed, soybean,
sunflower seed and mixtures thereof. [0076] BB) A composition for
hair growth comprising an oil formulation and an eicosanoid. [0077]
CC) The composition of embodiment BB wherein the oil formulation is
non-aqueous.
[0078] In order to improve eyelash/eyebrow hair growth products,
health and appearance enhancement and nutrients may be added to the
formulations. Uniquely for the eyelashes, ingredients to permit
curling (WO 2000074519, WO 2007078861, WO 20090136439 all of which
are incorporated by reference), and thereby enhancing appearance
and preventing impingement on the eyeball and ingrowth, would be
useful.
[0079] The invention pertains to non-aqueous formulations of
eicosanoids which allow the formulation to be preservative-free and
assists in the chemical stabilization of the active product
ingredient. Non-aqueous and non-preserved formulations containing
an eicosanoid, such as a prostanoid, and in particular bimatoprost,
tafluprost, or travoprost, and nutrient/health care ingredients
have been devised as described herein. These ingredients are
essential oils and plant oils. As preference, a cylindrical device
fitted with a felt/fiber tip is a method for eyelid margin
delivery. This delivery method results in economic advantages, such
as less waste since the product is applied only to the discrete
area requiring hypertrichosis and minimal unintentional retention
by the applicator compared to brushes. Dosing may be once every
other day, once a day, twice a day or three times a day. The
formulations may be applied to either the upper or lower eyelid
margin, eyebrows or the scalp.
[0080] The eyelash growth formulation may be delivered precisely to
the eyelid margin by the use of specialized devices designed for
the purpose. For example, specialized devices have been suggested
for this purpose of precision delivery to the required site (US
20070160562). Brush (WO2010065487) and roller devices (US
20070160562) have been contemplated at the contact end of the
device. The "tip" could also be in the form of a rotating cylinder
or a felt/fiber tip. To assist in accurately delivering a
therapeutic amount of the desired eicosanoid, a cylindrical
reservoir may be employed. The device may incorporate positive
displacement of the formulation by a plunger or by a ratchet that
may be turned to deliver the formulation. The cylinder reservoir
may be graduated to assist in quantifying drug delivery.
[0081] Direct delivery of the natural oil based drug formulation to
the required site of action, namely the eyelid margin, has certain
advantages. The spread of drug to areas where it can be of little
or no hypertrichotic benefit (for example on the upper eyelids or
eyelash hair shafts per se) is minimized. Direct delivery to the
eyelid margins also minimizes the possibility of drug accessing the
globe, where it would produce an unwanted decrease in intraocular
pressure. The use of a natural oil based vehicle with a felt/fiber
tip positive displacement device reduces waste. There is a
continuous flow/retention of formulation into the tip that is
easily replenished and which is not prone to evaporation. This
contrasts with aqueous formulations which are added to a brush, or
the brush is dipped into the aqueous formulation. In such cases,
most of the material remains unused in the brush and is lost by
disposal of the brush, and evaporation if the brush is retained and
used again contrary to the manufacturer's instructions. In some
cases, solution drip from the brush results in waste of material.
These brush application methods possess economic disadvantages that
are avoided by the inventions described herein.
[0082] Some eyelash formulations are listed below:
TABLE-US-00001 TABLE I Formulation No. 1 2 3 4 5 6 Bimatoprost
(w/v) 0.01% 0.02% 0.03% 0.01% 0.02% 0.03% Ethanol (v/v) 1% 1% 1% 1%
1% 1% Castor Oil (v/v) 3% 3% 3% 3% 3% 3% Jojoba Oil (v/v) 96% 96%
96% 94-95.5% .sup. 94-95.5% .sup. 94-95.5% .sup. Essential Oils
(v/v) 0% 0% 0% 0.5-2% .sup. 0.5-2% .sup. 0.5-2% .sup.
[0083] The invention includes concentrations of active agent
including 3.0% w/v to 0.001% w/v and including concentrations such
as 3.0%, 2.0%, 1.0% w/v, 0.9% w/v, 0.8% w/v, 0.7% w/v, 0.6% w/v,
0.5% w/v, 0.4% w/v, 0.3% w/v, 0.2% w/v, 0.1% w/v, 0.09% 0.08% w/v,
0.07% w/v, 0.06% w/v, 0.05% w/v, 0.04% w/v, 0.03% w/v, 0.02% w/v,
0.01% w/v, 0.009% w/v, 0.008% w/v, 0.007% w/v, 0.006% w/v, 0.005%
w/v, 0.004% w/v, 0.003% w/v, 0.002% w/v, 0.001% w/v, 0.009% w/v,
0.008% w/v, 0.007% w/v, 0.006% w/v, 0.005% w/v, 0.004% w/v, 0.003%
w/v, 0.002% w/v, and 0.001% w/v bimatoprost, travoprost, tafluprost
or latanoprost. Other oils include lavendar essential oil,
cedarwood essential oil, thyme essential oil, clary sage essential
oil and rosemary essential oil, avocado oil, sweet almond oil and
jojoba.
[0084] Additional eyelash formulations are below:
TABLE-US-00002 TABLE II Formulation No. 7 8 9 10 11 12 13 14 15 16
17 18 Bimatoprost (wt/v) % 0.01 0.01 0.01 0.01 0.02 0.02 0.02 0.02
0.03 0.03 0.03 0.03 Ethanol (v/v) % 1 1 1 1 1 1 1 1 1 1 1 1 Castor
Oil (v/v) % 3 3 3 3 3 3 3 3 3 3 3 3 Jojoba oil (v/v) % 95.6 71.6
71.6 71.6 95.6 71.6 71.6 71.6 95.6 71.6 71.6 71.6 Olive oil (v/v) %
24 12 24 12 24 12 Sweet almond 24 12 24 12 24 12 oil (v/v) %
Vitamin E (v/v) % 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.4
0.4
TABLE-US-00003 TABLE III Formulation No. 19 20 21 22 23 24 25
Bimatoprost (wt/v) % 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Ethanol (v/v) % 3
3 3 3 3 3 3 Castor Oil (v/v) % 3 3 3 3 3 3 3 Jojoba oil (v/v) %
68.5 68.5 68.5 68.5 68.5 68.5 68.5 Avocado oil (v/v) % 24 12 12 8
Olive oil (v/v) % 24 12 12 8 Sweet almond 24 12 12 8 oil (v/v) %
Rosemary Oil (v/v) % 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Tea tree oil (v/v)
% 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Vitamin E (v/v) % 0.5 0.5 0.5 0.5 0.5
0.5 0.5
TABLE-US-00004 TABLE IV Formulation No. 26 27 28 29 30 31 32
Bimatoprost (wt/v) % 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Ethanol (v/v) % 7
7 7 7 7 7 7 Castor Oil (v/v) % 3 3 3 3 3 3 3 Jojoba oil (v/v) %
64.5 64.5 64.5 64.5 64.5 64.5 64.5 Avocado oil (v/v) % 24 12 12 8
Olive oil (v/v) % 24 12 12 8 Sweet almond 24 12 12 8 oil (v/v) %
Rosemary Oil (v/v) % 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Tea tree oil (v/v)
% 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Vitamin E (v/v) % 0.5 0.5 0.5 0.5 0.5
0.5 0.5
[0085] Eyebrow growth formulations or scalp hair growth
formulations may be the same as those listed in Tables I-IV.
Dry Eye
[0086] It was discovered that the bimatoprost formulation provided
significant relief from dry eye symptoms. To better understand the
origin of this beneficial effect on dry eye symptomology, a
composition was formulated without bimatoprost or ethanol and
evaluated in human volunteers with dry eye symptomology.
Significant improvement or relief of dry eye was experienced.
TABLE-US-00005 TABLE V Formulation No. 33 Bimatoprost (w/v) 0.03%
Ethanol (v/v) 1% Castor Oil (v/v) 3% Jojoba Oil (v/v) 96% Essential
Oils (v/v) 0%
TABLE-US-00006 TABLE VI Formulation No. 34 Castor Oil (v/v) 3%
Jojoba Oil (v/v) 71.6% Sweet almond oil (v/v) 24% Vitamin E (v/v)
0.4%
[0087] Dry eye relief formulations may be the same as those listed
in Tables I-VI
[0088] Additional embodiments of the present invention include:
[0089] 1. In one embodiment is a formulation for the stimulation of
hair growth wherein the formulation is comprised of: [0090] at
least one eicosanoid; [0091] at least one oil; and [0092] at least
one alcohol; wherein [0093] the formulation is substantially free
of water; and [0094] the formulation is substantially free of
preservatives.
[0095] 2. The formulation of embodiment 1, wherein the
concentration of eicosanoid is from about 0.001% to about 5.0%.
[0096] 3. The formulation of embodiment 1, wherein the
concentration of eicosanoid is from about 0.01% to about 3.0%.
[0097] 4. The formulation of embodiment 1, wherein the
concentration of eicosanoid is from about 0.1% to about 0.3%.
[0098] 5. The formulation of embodiment 1, wherein the
concentration of eicosanoid is from about 0.01% to about 0.05%.
[0099] 6. The formulation of any one of embodiments 1-5, wherein
the eicosanoid is a prostanoid, leukotriene, lipoxin, resolvin, or
eoxin.
[0100] 7. The formulation of embodiment 6, wherein the eicosanoid
is a prostanoid.
[0101] 8. The formulation of embodiment 7, wherein the eicosanoid
is a prostanoid selected from prostaglandin F.sub.2.alpha.,
dinoprost, latanoprost, bimatoprost, travoprost, carboprost, and
tafluprost.
[0102] 9. The formulation of embodiment 8, wherein the prostanoid
is bimatoprost.
[0103] 10. The formulation of embodiment 8, wherein the prostanoid
is prostaglandin F.sub.2.alpha..
[0104] 11. The formulation of embodiment 8, wherein the prostanoid
is dinoprost.
[0105] 12. The formulation of embodiment 8, wherein the prostanoid
is latanoprost.
[0106] 13. The formulation of embodiment 8, wherein the prostanoid
is travoprost.
[0107] 14. The formulation of embodiment 8, wherein the prostanoid
is carboprost.
[0108] 15. The formulation of embodiment 8, wherein the prostanoid
is tafluprost.
[0109] 16. In one embodiment is a formulation for use in treating a
condition selected from the group consisting of hypotrichosis of
the eyelashes, hair loss of the eyebrows, hair loss of the scalp,
and hypotrichosis associated with chemotherapy treatment regimens,
wherein the formulation is comprised of: [0110] bimatoprost; [0111]
at least one oil; and [0112] at least one alcohol; wherein [0113]
the formulation is substantially free of water; and [0114] the
formulation is substantially free of preservatives.
[0115] 17. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 0.1% to about 99.0%.
[0116] 18. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 50.0% to about 99.0%.
[0117] 19. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 40.0% to about 50.0%.
[0118] 20. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 50.1% to about 60.0%.
[0119] 21. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 60.1% to about 70.0%.
[0120] 22. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 70.1% to about 80.0%.
[0121] 23. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 80.1% to about 90.0%.
[0122] 24. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 90.1% to about 99.0%.
[0123] 25. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 40.0% to about 55.0%.
[0124] 26. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 55.1% to about 70.0%.
[0125] 27. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 70.1% to about 85.0%.
[0126] 28. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is from about 85.1% to about 99.0%.
[0127] 29. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is about 93%.
[0128] 30. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is about 95%.
[0129] 31. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is about 97%.
[0130] 32. The formulation of any one of embodiments 1-16, wherein
the concentration of oil is about 99%.
[0131] 33. The formulation of any one of embodiments 1-32, wherein
the concentration of alcohol is from about 0.1% to about 50.0%.
[0132] 34. The formulation of any one of embodiments 1-32, wherein
the concentration of alcohol is from about 0.1% to about 20.0%.
[0133] 35. The formulation of any one of embodiments 1-32, wherein
the concentration of alcohol is from about 1.0% to about 15.0%.
[0134] 36. The formulation of any one of embodiments 1-32, wherein
the concentration of alcohol is from about 1.0% to about 10.0%.
[0135] 37. The formulation of any one of embodiments 1-32, wherein
the concentration of alcohol is from about 3.0% to about 10.0%.
[0136] 38. The formulation of any one of embodiments 1-32, wherein
the concentration of alcohol is from about 1.0% to about 5.0%.
[0137] 39. The formulation of any one of embodiments 1-32, wherein
the concentration of alcohol is from about 3.0% to about 8.0%.
[0138] 40. The formulation of any one of embodiments 1-32, wherein
the concentration of alcohol is from about 3.0% to about 5.0%.
[0139] 41. The formulation of any one of embodiments 1-40, wherein
substantially free of water is defined as less than 5.0%.
[0140] 42. The formulation of any one of embodiments 1-40, wherein
substantially free of water is defined as less than 2.0%.
[0141] 43. The formulation of any one of embodiments 1-40, wherein
substantially free of water is defined as less than 1.0%.
[0142] 44. The formulation of any one of embodiments 1-40, wherein
substantially free of water is defined as less than 0.5%.
[0143] 45. The formulation of any one of embodiments 1-40, wherein
substantially free of water is defined as less than 0.1%.
[0144] 46. The formulation of any one of embodiments 1-40, wherein
substantially free of water is defined as less than 0.05%.
[0145] 47. The formulation of any one of embodiments 1-40, wherein
substantially free of water is defined as less than 0.01%.
[0146] 48. The formulation of any one of embodiments 1-40, wherein
substantially free of water is defined as less than 0.005%.
[0147] 49. The formulation of any one of embodiments 1-40, wherein
substantially free of water is defined as less than 0.001%.
[0148] 50. The formulation of any one of embodiments 1-49, wherein
substantially free of preservative is defined as less than
5.0%.
[0149] 51. The formulation of any one of embodiments 1-49, wherein
substantially free of preservative is defined as less than
2.0%.
[0150] 52. The formulation of any one of embodiments 1-49, wherein
substantially free of preservative is defined as less than
1.0%.
[0151] 53. The formulation of any one of embodiments 1-49, wherein
substantially free of preservative is defined as less than
0.5%.
[0152] 54. The formulation of any one of embodiments 1-49, wherein
substantially free of preservative is defined as less than
0.1%.
[0153] 55. The formulation of any one of embodiments 1-49, wherein
substantially free of preservative is defined as less than
0.05%.
[0154] 56. The formulation of any one of embodiments 1-49, wherein
substantially free of preservative is defined as less than
0.01%.
[0155] 57. The formulation of any one of embodiments 1-49, wherein
substantially free of preservative is defined as less than
0.005%.
[0156] 58. The formulation of any one of embodiments 1-49, wherein
substantially free of preservative is defined as less than
0.001%.
[0157] 59. The formulation of embodiment 16, wherein the
concentration of bimatoprost is from about 0.001% to about
5.0%.
[0158] 60. The formulation of embodiment 16, wherein the
concentration of bimatoprost is from about 0.01% to about 3.0%.
[0159] 61. The formulation of embodiment 16, wherein the
concentration of bimatoprost is from about 0.01% to about 1.0%.
[0160] 62. The formulation of embodiment 16, wherein the
concentration of bimatoprost is from about 0.01% to about 0.5%.
[0161] 63. The formulation of embodiment 16, wherein the
concentration of bimatoprost is from about 0.02% to about 0.4%.
[0162] 64. The formulation of embodiment 16, wherein the
concentration of bimatoprost is from about 0.03% to about 0.3%.
[0163] 65. The formulation of embodiment 16, wherein the
concentration of bimatoprost is from about 0.1% to about 0.3%.
[0164] 66. The formulation of embodiment 16, wherein the
concentration of bimatoprost is from about 0.1% to about 0.2% 67.
The formulation of embodiment 16, wherein the concentration of
bimatoprost is from about 0.005% to about 0.05%.
[0165] 68. The formulation of embodiment 16, wherein the
concentration of bimatoprost is about 0.01%.
[0166] 69. The formulation of embodiment 16, wherein the
concentration of bimatoprost is about 0.02%.
[0167] 70. The formulation of embodiment 16, wherein the
concentration of bimatoprost is about 0.03%.
[0168] 71. The formulation of embodiment 16, wherein the
concentration of bimatoprost is about 0.04%.
[0169] 72. The formulation of embodiment 16, wherein the
concentration of bimatoprost is about 0.05%.
[0170] 73. The formulation of any one of embodiments 1-72 for use
in treating a condition selected from the group consisting of
hypotrichosis of the eyelashes, hair loss of the eyebrows, hair
loss of the scalp, and hypotrichosis associated with chemotherapy
treatment regimens.
[0171] 74. The formulation of any one of embodiments 1-73, for use
in treating hypotrichosis of the eyelashes.
[0172] 75. The formulation of any one of embodiments 1-73, for use
in treating hair loss of the eyebrows.
[0173] 76. The formulation of any one of embodiments 1-73, for use
in treating hair loss of the scalp.
[0174] 77. The formulation of any one of embodiments 1-73, for use
in treating hypotrichosis associated with chemotherapy treatment
regimens.
[0175] 78. The formulation of any one of embodiments 1-77, wherein
at least one alcohol is a C.sub.1-C.sub.20 alcohol.
[0176] 79. The formulation of embodiment 78, wherein the alcohol is
at least one C.sub.1-C.sub.10 alcohol.
[0177] 80. The formulation of embodiment 79, wherein the alcohol is
at least one C.sub.1-C.sub.6 alcohol.
[0178] 81. The formulation of embodiment 80, wherein the alcohol is
at least one C.sub.1-C.sub.3 alcohol.
[0179] 82. The formulation of embodiment 79, wherein at least one
alcohol is selected form the group of methanol, ethanol,
1-propanol, 1-butanol, 1-pentanol, propan-2-ol,
2-methylpropan-1-ol, butan-2-ol, 2-methylpropan-2-ol,
3-methylbutan-2-ol, 3-methylbutan-1-ol, 2-methylbutan-1-ol and
2-methylbutan-2-ol, pentan-3-ol, 2-methylpentan-2-ol,
2-methylpentan-3-ol, 4-methylpentan-2-ol, 4-methylpentan-1-ol,
2-methylpentan-1-ol, 3-methylpentan-1-ol, 3-methylpentan-2-ol,
3-methylpentan-3-ol, hexan-2-ol, hexan-3-ol, 2-methylhexan-1-ol,
2-methylhexan-2-ol, 2-methylhexan-3-ol, 5-methylhexan-3-ol,
5-methylhexan-2-ol, 5-methylhexan-1-ol, 3-methylhexan-1-ol,
3-methylhexan-2-ol, 3-methylhexan-3-ol, 4-methylhexan-3-ol,
4-methylhexan-2-ol, and 4-methylhexan-1-ol.
[0180] 83. The formulation of embodiment 82, wherein at least one
alcohol is selected from the group of ethanol, 1-propanol,
2-propanol and 1-butanol.
[0181] 84. The formulation of embodiment 83, wherein the alcohol is
ethanol.
[0182] 85. The formulation of embodiment 83, wherein the alcohol is
2-propanol.
[0183] 86. The formulation of any one of embodiments 1-85, wherein
at least one oil is a plant oil.
[0184] 87. The formulation of any one of embodiments 1-85, wherein
at least one oil is an animal oil.
[0185] 88. The formulation of any one of embodiments 1-85, wherein
at least one oil is a petroleum based oil.
[0186] 89. The formulation of any one of embodiments 1-85, wherein
at least one oil is not a plant or animal based oil.
[0187] 90. The formulation of any one of embodiments 1-85, wherein
at least one oil is selected from the group consisting of castor
oil, avocado oil, jojoba oil, olive oil, rosemary oil, tea tree
oil, sweet almond oil, and vitamin E.
[0188] 91. The formulation of any one of embodiments 1-85, wherein
at least one oil is selected from the group consisting of lavendar
essential oil, cedarwood essential oil, thyme essential oil, clary
sage essential oil, rosemary essential oil, polygonum multiflorum,
castor oil, jojoba oil, avocado oil, olive oil, sweet almond oil,
vitamin E.
[0189] 92. The formulation of any one of embodiments 1-85, wherein
at least two or more oils are selected from the group consisting of
avocado oil, olive oil, sweet almond oil, castor oil, rosemary oil,
tea tree oil, jojoba oil, and vitamin E.
[0190] 93. The formulation of any one of embodiments 1-92, wherein
the formulation is applied once every 7 days.
[0191] 94. The formulation of any one of embodiments 1-92, wherein
the formulation is applied once every 2 days.
[0192] 95. The formulation of any one of embodiments 1-92, wherein
the formulation is applied once per day.
[0193] 96. The formulation of any one of embodiments 1-92, wherein
the formulation is applied twice per day.
[0194] 97. The formulation of any one of embodiments 1-92, wherein
the formulation is applied three times per day.
[0195] 98. The formulation of any one of embodiments 1-97, wherein
the formulation is applied to an area of skin containing at least
one hair follicle.
[0196] 99. The formulation of any one of embodiments 1-97, wherein
the formulation is applied to an area selected from the group
consisting of upper eyelid margin, eyebrows and the scalp.
[0197] 100. The formulation of embodiment any one of embodiments
1-97, wherein the formulation is applied to the face, the scalp or
the body.
[0198] 101. The formulation of embodiment 100, wherein the
formulation is applied to the face.
[0199] 102. The formulation of any one of embodiments 1-101,
wherein the formulation is applied to at least one eyelid
margin.
[0200] 103. The formulation of embodiment 102, wherein the
formulation is applied to at least one upper eyelid margin.
[0201] 104. The formulation of any one of embodiments 1-103,
wherein the formulation elongates eyelash hairs by daily
application over a period of 60 days.
[0202] 105. The formulation of any one of embodiments 1-104,
wherein the formulation is applied by a multi-use applicator.
[0203] 106. The formulation of any one of embodiments 1-105,
wherein the alcohol is ethanol and the oil is a combination of
castor oil and jojoba oil.
[0204] 107. The formulation of embodiment 16, wherein the
formulation comprises about 0.02% w/v bimatoprost, about 1% v/v
ethanol, about 3% v/v castor oil, about 71.6% v/v jojoba oil, about
24% v/v sweet almond oil, and about 0.4% v/v Vitamin E.
[0205] 108. The formulation of embodiment 16, wherein the
formulation comprises 0.03% w/v bimatoprost, 7% v/v ethanol, 3% v/v
castor oil, 64.5% v/v jojoba oil, 12% v/v olive oil, 12% sweet
almond oil, 0.5% v/v Rosemary oil, 0.5% v/v tea tree oil and 0.5%
v/v Vitamin E.
[0206] 109. The formulation of embodiment 16, wherein the
formulation comprises 0.01% w/v bimatoprost, 3% v/v ethanol, 3% v/v
castor oil, 68.5% v/v jojoba oil, 8% v/v avocado oil, 8% v/v olive
oil, 8% v/v sweet almond oil, 0.5% v/v rosemary oil, 0.5% v/v tea
tree oil, 0.5% v/v Vitamin E.
[0207] 110. The formulation of embodiment 16, wherein the
formulation comprises 0.02%-0.03% w/v bimatoprost, about 1% v/v
ethanol, about 3% v/v castor oil, and about 70-96% v/v jojoba
oil.
[0208] 111. The formulation of embodiment 16, wherein [0209] the
concentration of bimatoprost is 0.02%; [0210] the formulation is
delivered to at least one upper eyelid margin; [0211] the
formulation is delivered with a multi-use applicator; and [0212]
the formulation results in equal or greater eyelash growth when
compared to a water-based formulation with a concentration of
bimatoprost of 0.03%.
[0213] 112. The formulation of embodiment 111, wherein the
water-based formulation is applied with a single use
applicator.
[0214] 113. The formulation of embodiment 111, wherein the
water-based formulation is applied with a brush contacting the
eyelashes.
[0215] 114. In one embodiment is a formulation for use in treating
a condition selected from the group consisting of hypotrichosis of
the eyelashes, hair loss of the eyebrows, hair loss of the scalp,
and hypotrichosis associated with chemotherapy treatment regimens,
wherein the formulation is comprised of bimatoprost and an
optionally substituted C.sub.7-C.sub.20 alkanol.
[0216] 115. The formulation of embodiment 114, wherein the
substituted C.sub.7-C.sub.20 alkyl is substituted with one or more
groups selected from: --OH, --O--R, --NH.sub.2, --NHR, --NR.sub.2,
--C(.dbd.O)H, --C(.dbd.O)R, --C(.dbd.O)OH, --C(.dbd.O)OR,
--OC(.dbd.O)R, --SH, --SR, and --S(.dbd.O).sub.2R; wherein R is
unsubstituted C.sub.1-C.sub.10 alkyl.
[0217] 116. The formulation of embodiment 115, wherein the
substituted C.sub.7-C.sub.20 alkyl is substituted with one or more
groups selected from: --OH, --O--R, --C(.dbd.O)OR, and
--OC(.dbd.O)R.
[0218] 117. In one embodiment is a formulation comprising
bimatoprost, an oil, and an alcohol, for use in: [0219] i) treating
a condition selected from the group consisting of hypotrichosis of
the [0220] eyelashes, hair loss of the eyebrows or hair loss of the
scalp; [0221] ii) regenerating hair on the face, scalp or body;
[0222] iii) modifying at least one hair in length, base
circumference, rigidity, or color; [0223] iv) increasing the number
of hairs per area of skin; or [0224] v) converting villous hair to
terminal hair.
[0225] 118. In one embodiment is a formulation for use in treating
a condition selected from the group consisting of hypotrichosis of
the eyelashes, hair loss of the eyebrows, hair loss of the scalp,
and hypotrichosis associated with chemotherapy treatment regimens,
wherein the formulation consists essentially of: [0226]
bimatoprost; [0227] at least one oil; and [0228] at least one
alcohol; wherein [0229] the formulation is substantially free of
water; and [0230] the formulation is substantially free of
preservatives.
[0231] 119. The formulation of embodiment 118, wherein the
concentration of oil is from about 0.1% to about 99.0%.
[0232] 120. The formulation of embodiment 118, wherein the
concentration of oil is from about 50.0% to about 99.0%.
[0233] 121. The formulation of embodiment 118, wherein the
concentration of oil is from about 40.0% to about 50.0%.
[0234] 122. The formulation of embodiment 118, wherein the
concentration of oil is from about 50.0% to about 60.0%.
[0235] 123. The formulation of embodiment 118, wherein the
concentration of oil is from about 60.0% to about 70.0%.
[0236] 124. The formulation of embodiment 118, wherein the
concentration of oil is from about 70.0% to about 80.0%.
[0237] 125. The formulation of embodiment 118, wherein the
concentration of oil is from about 80.0% to about 90.0%.
[0238] 126. The formulation of embodiment 118, wherein the
concentration of oil is from about 90.0% to about 99.0%.
[0239] 127. The formulation of embodiment 118, wherein the
concentration of oil is from about 40.0% to about 55.0%.
[0240] 128. The formulation of embodiment 118, wherein the
concentration of oil is from about 55.0% to about 70.0%.
[0241] 129. The formulation of embodiment 118, wherein the
concentration of oil is from about 70.0% to about 85.0%.
[0242] 130. The formulation of embodiment 118, wherein the
concentration of oil is from about 85.0% to about 99.0%.
[0243] 131. The formulation of embodiment 118, wherein the
concentration of oil is about 93%.
[0244] 132. The formulation of embodiment 118, wherein the
concentration of oil is about 95%.
[0245] 133. The formulation of embodiment 118, wherein the
concentration of oil is about 97%.
[0246] 134. The formulation of embodiment 118, wherein the
concentration of oil is about 99%.
[0247] 135. The formulation of any one of embodiments 118-134,
wherein the concentration of alcohol is from about 0.1% to about
50.0%.
[0248] 136. The formulation of any one of embodiments 118-134,
wherein the concentration of alcohol is from about 0.1% to about
20.0%.
[0249] 137. The formulation of any one of embodiments 118-134,
wherein the concentration of alcohol is from about 1.0% to about
15.0%.
[0250] 138. The formulation of any one of embodiments 118-134,
wherein the concentration of alcohol is from about 1.0% to about
10.0%.
[0251] 139. The formulation of any one of embodiments 118-134,
wherein the concentration of alcohol is from about 3.0% to about
10.0%.
[0252] 140. The formulation of any one of embodiments 118-134,
wherein the concentration of alcohol is from about 1.0% to about
5.0%.
[0253] 141. The formulation of any one of embodiments 118-134,
wherein the concentration of alcohol is from about 3.0% to about
8.0%.
[0254] 142. The formulation of any one of embodiments 118-134,
wherein the concentration of alcohol is from about 3.0% to about
5.0%.
[0255] 143. The formulation of any one of embodiments 118-142,
wherein substantially free is defined as less than 5.0%.
[0256] 144. The formulation of any one of embodiments 118-142,
wherein substantially free is defined as less than 2.0%.
[0257] 145. The formulation of any one of embodiments 118-142,
wherein substantially free is defined as less than 1.0%.
[0258] 146. The formulation of any one of embodiments 118-142,
wherein substantially free is defined as less than 0.5%.
[0259] 147. The formulation of any one of embodiments 118-142,
wherein substantially free is defined as less than 0.1%.
[0260] 148. The formulation of any one of embodiments 118-142,
wherein substantially free is defined as less than 0.05%.
[0261] 149. The formulation of any one of embodiments 118-142,
wherein substantially free is defined as less than 0.01%.
[0262] 150. The formulation of any one of embodiments 118-142,
wherein substantially free is defined as less than 0.005%.
[0263] 151. The formulation of any one of embodiments 118-142,
wherein substantially free is defined as less than 0.001%.
[0264] 152. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is from about 0.001% to
about 5.0%.
[0265] 153. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is from about 0.01% to
about 3.0%.
[0266] 154. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is from about 0.01% to
about 1.0%.
[0267] 155. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is from about 0.01% to
about 0.5%.
[0268] 156. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is from about 0.02% to
about 0.4%.
[0269] 157. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is from about 0.03% to
about 0.3%.
[0270] 158. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is from about 0.1% to
about 0.3%.
[0271] 159. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is from about 0.1% to
about 0.2%
[0272] 160. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is from about 0.005% to
about 0.05%.
[0273] 161. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is about 0.01%.
[0274] 162. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is about 0.02%.
[0275] 163. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is about 0.03%.
[0276] 164. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is about 0.04%.
[0277] 165. The formulation of any one of embodiments 118-151,
wherein the concentration of bimatoprost is about 0.05%.
[0278] 166. The formulation of any one of embodiments 118-165 for
use in treating a condition selected from the group consisting of
hypotrichosis of the eyelashes, hair loss of the eyebrows, hair
loss of the scalp, and hypotrichosis associated with chemotherapy
treatment regimens.
[0279] 167. The formulation of any one of embodiments 118-166, for
use in treating hypotrichosis of the eyelashes.
[0280] 168. The formulation of any one of embodiments 118-166, for
use in treating hair loss of the eyebrows.
[0281] 169. The formulation of any one of embodiments 118-166, for
use in treating hair loss of the scalp.
[0282] 170. The formulation of any one of embodiments 118-166, for
use in treating hypotrichosis associated with chemotherapy
treatment regimens.
[0283] 171. The formulation of any one of embodiments 118-170,
wherein the alcohol is a C.sub.1-C.sub.20 alcohol.
[0284] 172. The formulation of embodiment 171, wherein the alcohol
is a C.sub.1-C.sub.10 alcohol.
[0285] 173. The formulation of embodiment 172, wherein the alcohol
is a C.sub.1-C.sub.6 alcohol.
[0286] 174. The formulation of embodiment 173, wherein the alcohol
is a C.sub.1-C.sub.3 alcohol.
[0287] 175. The formulation of embodiment 172, wherein the alcohol
is selected form the group of methanol, ethanol, 1-propanol,
1-butanol, 1-pentanol, propan-2-ol, 2-methylpropan-1-ol,
butan-2-ol, 2-methylpropan-2-ol, 3-methylbutan-2-ol,
3-methylbutan-1-ol, 2-methylbutan-1-ol and 2-methylbutan-2-ol,
pentan-3-ol, 2-methylpentan-2-ol, 2-methylpentan-3-ol,
4-methylpentan-2-ol, 4-methylpentan-1-ol, 2-methylpentan-1-ol,
3-methylpentan-1-ol, 3-methylpentan-2-ol, 3-methylpentan-3-ol,
hexan-2-ol, hexan-3-ol, 2-methylhexan-1-ol, 2-methylhexan-2-ol,
2-methylhexan-3-ol, 5-methylhexan-3-ol, 5-methylhexan-2-ol,
5-methylhexan-1-ol, 3-methylhexan-1-ol, 3-methylhexan-2-ol,
3-methylhexan-3-ol, 4-methylhexan-3-ol, 4-methylhexan-2-ol, and
4-methylhexan-1-ol.
[0288] 176. The formulation of embodiment 175, wherein the alcohol
is selected form the group of ethanol, 1-propanol, 2-propanol and
1-butanol.
[0289] 177. The formulation of embodiment 176, wherein the alcohol
is ethanol.
[0290] 178. The formulation of any one of embodiments 118-177,
wherein the oil is a plant oil.
[0291] 179. The formulation of any one of embodiments 118-177,
wherein the oil is an animal oil.
[0292] 180. The formulation of any one of embodiments 118-177,
wherein the oil is a petroleum based oil.
[0293] 181. The formulation of any one of embodiments 118-177,
wherein the oil is not a plant or animal based oil.
[0294] 182. The formulation of any one of embodiments 118-177,
wherein the oil is selected from the group consisting of castor
oil, avocado oil, jojoba oil, olive oil, rosemary oil, tea tree
oil, sweet almond oil, and vitamin E.
[0295] 183. The formulation of any one of embodiments 118-177,
wherein the oil is selected from the group consisting of lavendar
essential oil, cedar wood essential oil, thyme essential oil, clary
sage essential oil, rosemary essential oil, polygonum multiflorum,
castor oil, jojoba oil, avocado oil, olive oil, sweet almond oil,
vitamin E.
[0296] 184. The formulation of any one of embodiments 118-177,
wherein two or more oils are used selected from the group
consisting of avocado oil, olive oil, sweet almond oil, castor oil,
rosemary oil, tea tree oil, jojoba oil, and vitamin E.
[0297] 185. The formulation of any one of embodiments 118-184,
wherein the formulation is applied once every 7 days.
[0298] 186. The formulation of any one of embodiments 118-184,
wherein the formulation is applied once every 2 days.
[0299] 187. The formulation of any one of embodiments 118-184,
wherein the formulation is applied once per day.
[0300] 188. The formulation of any one of embodiments 118-184,
wherein the formulation is applied twice per day.
[0301] 189. The formulation of any one of embodiments 118-184,
wherein the formulation is applied three times per day.
[0302] 190. The formulation of any one of embodiments 118-184,
wherein the formulation is applied to an area of skin containing at
least one hair follicle.
[0303] 191. The formulation of any one of embodiments 118-184,
wherein the formulation is applied to an area selected from the
group consisting of upper eyelid margin, eyebrows and the
scalp.
[0304] 192. The formulation of embodiment any one of embodiments
118-184, wherein the formulation is applied to an area of skin
selected from the group consisting of the face, the scalp and the
body.
[0305] 193. The formulation of embodiment 192, wherein the
formulation is applied to the face.
[0306] 194. The formulation of any one of embodiments 118-184,
wherein the formulation is applied to at least one eyelid
margin.
[0307] 195. The formulation of embodiment 194, wherein the
formulation is applied to at least one upper eyelid margin.
[0308] 196. The formulation of any one of embodiments 118-195,
wherein the formulation elongates eyelash hairs by daily
application over a period of 60 days.
[0309] 197. The formulation of any one of embodiments 118-196,
wherein the formulation is applied by a multi-use applicator.
[0310] 198. The formulation of embodiment 118, wherein the alcohol
is ethanol, and the oil is a combination of castor oil and jojoba
oil.
[0311] 199. The formulation of embodiment 118, wherein the
formulation comprises about 0.02% w/v bimatoprost, about 1% v/v
ethanol, about 3% v/v castor oil, about 71.6% v/v jojoba oil, about
24% v/v sweet almond oil, and about 0.4% v/v Vitamin E.
[0312] 200. The formulation of embodiment 118, wherein the
formulation comprises 0.3% w/v bimatoprost, 7% v/v ethanol, 3% v/v
castor oil, 64.5% v/v jojoba oil, 12% v/v olive oil, 12% sweet
almond oil, 0.5% v/v Rosemary oil, 0.5% v/v tea tree oil and 0.5%
v/v Vitamin E.
[0313] 201. The formulation of embodiment 118, wherein the
formulation comprises 0.1% w/v bimatoprost, 3% v/v ethanol, 3% v/v
castor oil, 68.5% v/v jojoba oil, 8% v/v avocado oil, 8% v/v olive
oil, 8% v/v sweet almond oil, 0.5% v/v rosemary oil, 0.5% v/v tea
tree oil, 0.5% v/v Vitamin E.
[0314] 202. The formulation of embodiment 118, wherein the
formulation comprises 0.02%-0.03% w/v bimatoprost, about 1% v/v
ethanol, about 3% v/v castor oil, and about 70-96% v/v jojoba
oil.
[0315] 203. The formulation of embodiment 118, wherein the
concentration of bimatoprost is 0.02%; [0316] the formulation is
delivered to at least one upper eyelid margin; [0317] the
formulation is delivered with a multi-use applicator; and [0318]
the formulation results in equal or greater eyelash growth when
compared to a [0319] water-based formulation with a concentration
of bimatoprost of 0.03%.
[0320] 204. The formulation of embodiment 203, wherein the
water-based formulation is applied with a single use
applicator.
[0321] 205. The formulation of embodiment 203, wherein the
water-based formulation is applied with a brush contacting the
eyelashes.
[0322] 206. In one embodiment is a method for use in treating a
condition selected from the group consisting of hypotrichosis of
the eyelashes, hair loss of the eyebrows, hair loss of the scalp,
and hypotrichosis associated with chemotherapy treatment regimens,
comprising administrating to the patient a formulation comprised
of: [0323] at least one eicosanoid; [0324] at least one oil; and
[0325] at least one alcohol; wherein [0326] the formulation is
substantially free of water; and [0327] the formulation is
substantially free of preservatives.
[0328] 207. The method of embodiment 206, wherein the concentration
of eicosanoid is from about 0.001% to about 5.0%.
[0329] 208. The method of embodiment 206, wherein the concentration
of eicosanoid is from about 0.01% to about 3.0%.
[0330] 209. The method of embodiment 206, wherein the concentration
of eicosanoid is from about 0.1% to about 0.3%.
[0331] 210. The method of embodiment 206, wherein the concentration
of eicosanoid is from about 0.01% to about 0.05%.
[0332] 211. The method of any one of embodiments 206-210, wherein
the eicosanoid is a prostanoid, leukotriene, lipoxin, resolvin, or
eoxin.
[0333] 212. The method of embodiment 211, wherein the eicosanoid is
a prostanoid.
[0334] 213. The method of embodiment 212, wherein the eicosanoid is
a prostanoid selected from prostaglandin F.sub.2.alpha., dinoprost,
latanoprost, bimatoprost, travoprost, carboprost, and
tafluprost.
[0335] 214. The method of embodiment 213, wherein the prostanoid is
bimatoprost.
[0336] 215. The method of embodiment 213, wherein the prostanoid is
prostaglandin F.sub.2.alpha..
[0337] 216. The method of embodiment 213, wherein the prostanoid is
dinoprost.
[0338] 217. The method of embodiment 213, wherein the prostanoid is
latanoprost.
[0339] 218. The method of embodiment 213, wherein the prostanoid is
travoprost.
[0340] 219. The method of embodiment 213, wherein the prostanoid is
carboprost.
[0341] 220. The method of embodiment 213, wherein the prostanoid is
tafluprost.
[0342] 221. In one embodiment is a method for use in treating a
condition selected from the group consisting of hypotrichosis of
the eyelashes, hair loss of the eyebrows, hair loss of the scalp,
and hypotrichosis associated with chemotherapy treatment regimens,
comprising administrating to the patient a formulation comprised
of: [0343] bimatoprost; [0344] at least one oil; and [0345] at
least one alcohol; wherein [0346] the formulation is substantially
free of water; and [0347] the formulation is substantially free of
preservatives.
[0348] 222. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 0.1% to about 99.0%.
[0349] 223. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 50.0% to about 99.0%.
[0350] 224. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 40.0% to about 50.0%.
[0351] 225. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 50.1% to about 60.0%.
[0352] 226. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 60.1% to about 70.0%.
[0353] 227. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 70.1% to about 80.0%.
[0354] 228. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 80.1% to about 90.0%.
[0355] 229. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 90.1% to about 99.0%.
[0356] 230. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 40.0% to about 55.0%.
[0357] 231. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 55.1% to about 70.0%.
[0358] 232. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 70.1% to about 85.0%.
[0359] 233. The method of any one of embodiments 206-221, wherein
the concentration of oil is from about 85.1% to about 99.0%.
[0360] 234. The method of any one of embodiments 206-221, wherein
the concentration of oil is about 93%.
[0361] 235. The method of any one of embodiments 206-221, wherein
the concentration of oil is about 95%.
[0362] 236. The method of any one of embodiments 206-221, wherein
the concentration of oil is about 97%.
[0363] 237. The method of any one of embodiments 206-221, wherein
the concentration of oil is about 99%.
[0364] 238. The method of any one of embodiments 206-237, wherein
the concentration of alcohol is from about 0.1% to about 50.0%.
[0365] 239. The method of any one of embodiments 206-237, wherein
the concentration of alcohol is from about 0.1% to about 20.0%.
[0366] 240. The method of any one of embodiments 206-237, wherein
the concentration of alcohol is from about 1.0% to about 15.0%.
[0367] 241. The method of any one of embodiments 206-237, wherein
the concentration of alcohol is from about 1.0% to about 10.0%.
[0368] 242. The method of any one of embodiments 206-237, wherein
the concentration of alcohol is from about 3.0% to about 10.0%.
[0369] 243. The method of any one of embodiments 206-237, wherein
the concentration of alcohol is from about 1.0% to about 5.0%.
[0370] 244. The method of any one of embodiments 206-237, wherein
the concentration of alcohol is from about 3.0% to about 8.0%.
[0371] 245. The method of any one of embodiments 206-237, wherein
the concentration of alcohol is from about 3.0% to about 5.0%.
[0372] 246. The method of any one of embodiments 206-245, wherein
substantially free of water is defined as less than 5.0%.
[0373] 247. The method of any one of embodiments 206-245, wherein
substantially free of water is defined as less than 2.0%.
[0374] 248. The method of any one of embodiments 206-245, wherein
substantially free of water is defined as less than 1.0%.
[0375] 249. The method of any one of embodiments 206-245, wherein
substantially free of water is defined as less than 0.5%.
[0376] 250. The method of any one of embodiments 206-245, wherein
substantially free of water is defined as less than 0.1%.
[0377] 251. The method of any one of embodiments 206-245, wherein
substantially free of water is defined as less than 0.05%.
[0378] 252. The method of any one of embodiments 206-245, wherein
substantially free of water is defined as less than 0.01%.
[0379] 253. The method of any one of embodiments 206-245, wherein
substantially free of water is defined as less than 0.005%.
[0380] 254. The method of any one of embodiments 206-245, wherein
substantially free of water is defined as less than 0.001%.
[0381] 255. The method of any one of embodiments 206-245, wherein
substantially free of preservative is defined as less than
5.0%.
[0382] 256. The method of any one of embodiments 206-245, wherein
substantially free of preservative is defined as less than
2.0%.
[0383] 257. The method of any one of embodiments 206-245, wherein
substantially free of preservative is defined as less than
1.0%.
[0384] 258. The method of any one of embodiments 206-245, wherein
substantially free of preservative is defined as less than
0.5%.
[0385] 259. The method of any one of embodiments 206-245, wherein
substantially free of preservative is defined as less than
0.1%.
[0386] 260. The method of any one of embodiments 206-245, wherein
substantially free of preservative is defined as less than
0.05%.
[0387] 261. The method of any one of embodiments 206-245, wherein
substantially free of preservative is defined as less than
0.01%.
[0388] 262. The method of any one of embodiments 206-245, wherein
substantially free of preservative is defined as less than
0.005%.
[0389] 263. The method of any one of embodiments 206-245, wherein
substantially free of preservative is defined as less than
0.001%.
[0390] 264. The method of embodiment 221, wherein the concentration
of bimatoprost is from about 0.001% to about 5.0%.
[0391] 265. The method of embodiment 221, wherein the concentration
of bimatoprost is from about 0.01% to about 3.0%.
[0392] 266. The method of embodiment 221, wherein the concentration
of bimatoprost is from about 0.01% to about 1.0%.
[0393] 267. The method of embodiment 221, wherein the concentration
of bimatoprost is from about 0.01% to about 0.5%.
[0394] 268. The method of embodiment 221, wherein the concentration
of bimatoprost is from about 0.02% to about 0.4%.
[0395] 269. The method of embodiment 221, wherein the concentration
of bimatoprost is from about 0.03% to about 0.3%.
[0396] 270. The method of embodiment 221, wherein the concentration
of bimatoprost is from about 0.1% to about 0.3%.
[0397] 271. The method of embodiment 221, wherein the concentration
of bimatoprost is from about 0.1% to about 0.2% 272. The method of
embodiment 221, wherein the concentration of bimatoprost is from
about 0.005% to about 0.05%.
[0398] 273. The method of embodiment 221, wherein the concentration
of bimatoprost is about 0.01%.
[0399] 274. The method of embodiment 221, wherein the concentration
of bimatoprost is about 0.02%.
[0400] 275. The method of embodiment 221, wherein the concentration
of bimatoprost is about 0.03%.
[0401] 276. The method of embodiment 221, wherein the concentration
of bimatoprost is about 0.04%.
[0402] 277. The method of embodiment 221, wherein the concentration
of bimatoprost is about 0.05%.
[0403] 278. The method of any one of embodiments 206-277 for use in
treating a condition selected from the group consisting of
hypotrichosis of the eyelashes, hair loss of the eyebrows, hair
loss of the scalp, and hypotrichosis associated with chemotherapy
treatment regimens.
[0404] 279. The method of any one of embodiments 206-278, for use
in treating hypotrichosis of the eyelashes.
[0405] 280. The method of any one of embodiments 206-278, for use
in treating hair loss of the eyebrows.
[0406] 281. The method of any one of embodiments 206-278, for use
in treating hair loss of the scalp.
[0407] 282. The method of any one of embodiments 206-278, for use
in treating hypotrichosis associated with chemotherapy treatment
regimens.
[0408] 283. The method of any one of embodiments 206-282, wherein
at least one alcohol is a C.sub.1-C.sub.20 alcohol.
[0409] 284. The method of embodiment 283, wherein the alcohol is at
least one C.sub.1-C.sub.10 alcohol.
[0410] 285. The method of embodiment 284, wherein the alcohol is at
least one C.sub.1-C.sub.6 alcohol.
[0411] 286. The method of embodiment 285, wherein the alcohol is at
least one C.sub.1-C.sub.3 alcohol.
[0412] 287. The method of embodiment 284, wherein at least one
alcohol is selected form the group of methanol, ethanol,
1-propanol, 1-butanol, 1-pentanol, propan-2-ol,
2-methylpropan-1-ol, butan-2-ol, 2-methylpropan-2-ol,
3-methylbutan-2-ol, 3-methylbutan-1-ol, 2-methylbutan-1-ol and
2-methylbutan-2-ol, pentan-3-ol, 2-methylpentan-2-ol,
2-methylpentan-3-ol, 4-methylpentan-2-ol, 4-methylpentan-1-ol,
2-methylpentan-1-ol, 3-methylpentan-1-ol, 3-methylpentan-2-ol,
3-methylpentan-3-ol, hexan-2-ol, hexan-3-ol, 2-methylhexan-1-ol,
2-methylhexan-2-ol, 2-methylhexan-3-ol, 5-methylhexan-3-ol,
5-methylhexan-2-ol, 5-methylhexan-1-ol, 3-methylhexan-1-ol,
3-methylhexan-2-ol, 3-methylhexan-3-ol, 4-methylhexan-3-ol,
4-methylhexan-2-ol, and 4-methylhexan-1-ol.
[0413] 288. The method of embodiment 287, wherein at least one
alcohol is selected form the group of ethanol, 1-propanol,
2-propanol and 1-butanol.
[0414] 289. The method of embodiment 288, wherein the alcohol is
ethanol.
[0415] 290. The method of any one of embodiments 206-289, wherein
at least one oil is a plant oil.
[0416] 291. The method of any one of embodiments 206-289, wherein
at least one oil is an animal oil.
[0417] 292. The method of any one of embodiments 206-289, wherein
at least one oil is a petroleum based oil.
[0418] 293. The method of any one of embodiments 206-289, wherein
at least one oil is not a plant or animal based oil.
[0419] 294. The method of any one of embodiments 206-289, wherein
at least one oil is selected from the group consisting of castor
oil, avocado oil, jojoba oil, olive oil, rosemary oil, tea tree
oil, sweet almond oil, and vitamin E.
[0420] 295. The method of any one of embodiments 206-289, wherein
at least one oil is selected from the group consisting of lavendar
essential oil, cedar wood essential oil, thyme essential oil, clary
sage essential oil, rosemary essential oil, polygonum multiflorum,
castor oil, jojoba oil, avocado oil, olive oil, sweet almond oil,
vitamin E.
[0421] 296. The method of any one of embodiments 206-289, wherein
at least two or more oils are selected from the group consisting of
avocado oil, olive oil, sweet almond oil, castor oil, rosemary oil,
tea tree oil, jojoba oil, and vitamin E.
[0422] 297. The method of any one of embodiments 206-296, wherein
the formulation is applied once every 7 days.
[0423] 298. The method of any one of embodiments 206-296, wherein
the formulation is applied once every 2 days.
[0424] 299. The method of any one of embodiments 206-296, wherein
the formulation is applied once per day.
[0425] 300. The method of any one of embodiments 206-296, wherein
the formulation is applied twice per day.
[0426] 301. The method of any one of embodiments 206-296, wherein
the formulation is applied three times per day.
[0427] 302. The method of any one of embodiments 206-301, wherein
the formulation is applied to an area of skin containing at least
one hair follicle.
[0428] 303. The method of any one of embodiments 206-301, wherein
the formulation is applied to an area selected from the group
consisting of upper eyelid margin, eyebrows and the scalp.
[0429] 304. The method of embodiment any one of embodiments
206-301, wherein the formulation is applied to the face, the scalp
or the body.
[0430] 305. The method of embodiment 304, wherein the formulation
is applied to the face.
[0431] 306. The method of any one of embodiments 206-305, wherein
the formulation is applied to at least one eyelid margin.
[0432] 307. The method of embodiment 306, wherein the formulation
is applied to at least one upper eyelid margin.
[0433] 308. The method of any one of embodiments 206-307, wherein
the formulation elongates eyelash hairs by daily application over a
period of 60 days.
[0434] 309. The method of any one of embodiments 206-308, wherein
the formulation is applied by a multi-use applicator.
[0435] 310. The method of any one of embodiments 206-309, wherein
the alcohol is ethanol, and the oil is a combination of castor oil
and jojoba oil.
[0436] 311. The method of embodiment 221, wherein the formulation
comprises about 0.02% w/v bimatoprost, about 1% v/v ethanol, about
3% v/v castor oil, about 71.6% v/v jojoba oil, about 24% v/v sweet
almond oil, and about 0.4% v/v Vitamin E.
[0437] 312. The method of embodiment 221, wherein the formulation
comprises 0.3% w/v bimatoprost, 7% v/v ethanol, 3% v/v castor oil,
64.5% v/v jojoba oil, 12% v/v olive oil, 12% sweet almond oil, 0.5%
v/v Rosemary oil, 0.5% v/v tea tree oil and 0.5% v/v Vitamin E.
[0438] 313. The method of embodiment 221, wherein the formulation
comprises 0.1% w/v bimatoprost, 3% v/v ethanol, 3% v/v castor oil,
68.5% v/v jojoba oil, 8% v/v avocado oil, 8% v/v olive oil, 8% v/v
sweet almond oil, 0.5% v/v rosemary oil, 0.5% v/v tea tree oil,
0.5% v/v Vitamin E.
[0439] 314. The method of embodiment 221, wherein the formulation
comprises 0.02%-0.03% w/v bimatoprost, about 1% v/v ethanol, about
3% v/v castor oil, and about 70-96% v/v jojoba oil.
[0440] 315. The method of embodiment 221, wherein [0441] the
concentration of bimatoprost is 0.02%; [0442] the formulation is
delivered to at least one upper eyelid margin; [0443] the
formulation is delivered with a multi-use applicator; and [0444]
the formulation results in equal or greater eyelash growth when
compared to a water-based formulation with a concentration of
bimatoprost of 0.03%.
[0445] 316. The method of embodiment 315, wherein the comparison
water-based formulation is applied with a single use
applicator.
[0446] 317. The method of embodiment 315, wherein the comparison
water-based formulation is applied with a brush contacting the
eyelashes.
[0447] 318. In one embodiment is a method for use in treating a
condition selected from the group consisting of hypotrichosis of
the eyelashes, hair loss of the eyebrows, hair loss of the scalp,
and hypotrichosis associated with chemotherapy treatment regimens,
comprising administrating to the patient a formulation consisting
essentially of: [0448] bimatoprost; [0449] at least one oil; and
[0450] at least one alcohol; wherein [0451] the formulation is
substantially free of water; and [0452] the formulation is
substantially free of preservatives.
[0453] 319. The method of embodiment 318, wherein the concentration
of oil is from about 0.1% to about 99.0%.
[0454] 320. The method of embodiment 318, wherein the concentration
of oil is from about 50.0% to about 99.0%.
[0455] 321. The method of embodiment 318, wherein the concentration
of oil is from about 40.0% to about 50.0%.
[0456] 322. The method of embodiment 318, wherein the concentration
of oil is from about 50.0% to about 60.0%.
[0457] 323. The method of embodiment 318, wherein the concentration
of oil is from about 60.0% to about 70.0%.
[0458] 324. The method of embodiment 318, wherein the concentration
of oil is from about 70.0% to about 80.0%.
[0459] 325. The method of embodiment 318, wherein the concentration
of oil is from about 80.0% to about 90.0%.
[0460] 326. The method of embodiment 318, wherein the concentration
of oil is from about 90.0% to about 99.0%.
[0461] 327. The method of embodiment 318, wherein the concentration
of oil is from about 40.0% to about 55.0%.
[0462] 328. The method of embodiment 318, wherein the concentration
of oil is from about 55.0% to about 70.0%.
[0463] 329. The method of embodiment 318, wherein the concentration
of oil is from about 70.0% to about 85.0%.
[0464] 330. The method of embodiment 318, wherein the concentration
of oil is from about 85.0% to about 99.0%.
[0465] 331. The method of embodiment 318, wherein the concentration
of oil is about 93%.
[0466] 332. The method of embodiment 318, wherein the concentration
of oil is about 95%.
[0467] 333. The method of embodiment 318, wherein the concentration
of oil is about 97%.
[0468] 334. The method of embodiment 318, wherein the concentration
of oil is about 99%.
[0469] 335. The method of any one of embodiments 318-334, wherein
the concentration of alcohol is from about 0.1% to about 50.0%.
[0470] 336. The method of any one of embodiments 318-334, wherein
the concentration of alcohol is from about 0.1% to about 20.0%.
[0471] 337. The method of any one of embodiments 318-334, wherein
the concentration of alcohol is from about 1.0% to about 15.0%.
[0472] 338. The method of any one of embodiments 318-334, wherein
the concentration of alcohol is from about 1.0% to about 10.0%.
[0473] 339. The method of any one of embodiments 318-334, wherein
the concentration of alcohol is from about 3.0% to about 10.0%.
[0474] 340. The method of any one of embodiments 318-334, wherein
the concentration of alcohol is from about 1.0% to about 5.0%.
[0475] 341. The method of any one of embodiments 318-334, wherein
the concentration of alcohol is from about 3.0% to about 8.0%.
[0476] 342. The method of any one of embodiments 318-334, wherein
the concentration of alcohol is from about 3.0% to about 5.0%.
[0477] 343. The method of any one of embodiments 318-342, wherein
substantially free is defined as less than 5.0%.
[0478] 344. The method of any one of embodiments 318-342, wherein
substantially free is defined as less than 2.0%.
[0479] 345. The method of any one of embodiments 318-342, wherein
substantially free is defined as less than 1.0%.
[0480] 346. The method of any one of embodiments 318-342, wherein
substantially free is defined as less than 0.5%.
[0481] 347. The method of any one of embodiments 318-342, wherein
substantially free is defined as less than 0.1%.
[0482] 348. The method of any one of embodiments 318-342, wherein
substantially free is defined as less than 0.05%.
[0483] 349. The method of any one of embodiments 318-342, wherein
substantially free is defined as less than 0.01%.
[0484] 350. The method of any one of embodiments 318-342, wherein
substantially free is defined as less than 0.005%.
[0485] 351. The method of any one of embodiments 318-342, wherein
substantially free is defined as less than 0.001%.
[0486] 352. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is from about 0.001% to about
5.0%.
[0487] 353. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is from about 0.01% to about
3.0%.
[0488] 354. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is from about 0.01% to about
1.0%.
[0489] 355. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is from about 0.01% to about
0.5%.
[0490] 356. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is from about 0.02% to about
0.4%.
[0491] 357. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is from about 0.03% to about
0.3%.
[0492] 358. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is from about 0.1% to about
0.3%.
[0493] 359. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is from about 0.1% to about
0.2%
[0494] 360. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is from about 0.005% to about
0.05%.
[0495] 361. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is about 0.01%.
[0496] 362. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is about 0.02%.
[0497] 363. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is about 0.03%.
[0498] 364. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is about 0.04%.
[0499] 365. The method of any one of embodiments 318-351, wherein
the concentration of bimatoprost is about 0.05%.
[0500] 366. The method of any one of embodiments 318-365 for use in
treating a condition selected from the group consisting of
hypotrichosis of the eyelashes, hair loss of the eyebrows, hair
loss of the scalp, and hypotrichosis associated with chemotherapy
treatment regimens.
[0501] 367. The method of any one of embodiments 318-366, for use
in treating hypotrichosis of the eyelashes.
[0502] 368. The method of any one of embodiments 318-366, for use
in treating hair loss of the eyebrows.
[0503] 369. The method of any one of embodiments 318-366, for use
in treating hair loss of the scalp.
[0504] 370. The method of any one of embodiments 318-366, for use
in treating hypotrichosis associated with chemotherapy treatment
regimens.
[0505] 371. The method of any one of embodiments 318-370, wherein
the alcohol is a C.sub.1-C.sub.20 alcohol.
[0506] 372. The method of embodiment 371, wherein the alcohol is a
C.sub.1-C.sub.10 alcohol.
[0507] 373. The method of embodiment 372, wherein the alcohol is a
C.sub.1-C.sub.6 alcohol.
[0508] 374. The method of embodiment 373, wherein the alcohol is a
C.sub.1-C.sub.3 alcohol.
[0509] 375. The method of embodiment 373, wherein the alcohol is
selected form the group of methanol, ethanol, 1-propanol,
1-butanol, 1-pentanol, propan-2-ol, 2-methylpropan-1-ol,
butan-2-ol, 2-methylpropan-2-ol, 3-methylbutan-2-ol,
3-methylbutan-1-ol, 2-methylbutan-1-ol and 2-methylbutan-2-ol,
pentan-3-ol, 2-methylpentan-2-ol, 2-methylpentan-3-ol,
4-methylpentan-2-ol, 4-methylpentan-1-ol, 2-methylpentan-1-ol,
3-methylpentan-1-ol, 3-methylpentan-2-ol, 3-methylpentan-3-ol,
hexan-2-ol, hexan-3-ol, 2-methylhexan-1-ol, 2-methylhexan-2-ol,
2-methylhexan-3-ol, 5-methylhexan-3-ol, 5-methylhexan-2-ol,
5-methylhexan-1-ol, 3-methylhexan-1-ol, 3-methylhexan-2-ol,
3-methylhexan-3-ol, 4-methylhexan-3-ol, 4-methylhexan-2-ol, and
4-methylhexan-1-ol.
[0510] 376. The method of embodiment 175, wherein the alcohol is
selected form the group of ethanol, 1-propanol, 2-propanol and
1-butanol.
[0511] 377. The method of embodiment 376, wherein the alcohol is
ethanol.
[0512] 378. The method of any one of embodiments 318-377, wherein
the oil is a plant oil.
[0513] 379. The method of any one of embodiments 318-377, wherein
the oil is an animal oil.
[0514] 380. The method of any one of embodiments 318-377, wherein
the oil is a petroleum based oil.
[0515] 381. The method of any one of embodiments 318-377, wherein
the oil is not a plant or animal based oil.
[0516] 382. The method of any one of embodiments 318-377, wherein
the oil is selected from the group consisting of castor oil,
avocado oil, jojoba oil, olive oil, rosemary oil, tea tree oil,
sweet almond oil, and vitamin E.
[0517] 383. The method of any one of embodiments 318-377, wherein
the oil is selected from the group consisting of lavendar essential
oil, cedar wood essential oil, thyme essential oil, clary sage
essential oil, rosemary essential oil, polygonum multiflorum,
castor oil, jojoba oil, avocado oil, olive oil, sweet almond oil,
vitamin E.
[0518] 384. The method of any one of embodiments 318-377, wherein
two or more oils are used selected from the group consisting of
avocado oil, olive oil, sweet almond oil, castor oil, rosemary oil,
tea tree oil, jojoba oil, and vitamin E.
[0519] 385. The method of any one of embodiments 318-384, wherein
the formulation is applied once every 7 days.
[0520] 386. The method of any one of embodiments 318-384, wherein
the formulation is applied once every 2 days.
[0521] 387. The method of any one of embodiments 318-384, wherein
the formulation is applied once per day.
[0522] 388. The method of any one of embodiments 318-384, wherein
the formulation is applied twice per day.
[0523] 389. The method of any one of embodiments 318-384, wherein
the formulation is applied three times per day.
[0524] 390. The method of any one of embodiments 318-384, wherein
the formulation is applied to an area of skin containing at least
one hair follicle.
[0525] 391. The method of any one of embodiments 318-384, wherein
the formulation is applied to an area selected from the group
consisting of upper eyelid margin, eyebrows and the scalp.
[0526] 392. The method of embodiment any one of embodiments
318-384, wherein the formulation is applied to an area of skin
selected from the group consisting of the face, the scalp and the
body.
[0527] 393. The method of embodiment 392, wherein the formulation
is applied to the face.
[0528] 394. The method of any one of embodiments 318-384, wherein
the formulation is applied to at least one eyelid margin.
[0529] 395. The method of embodiment 394, wherein the formulation
is applied to at least one upper eyelid margin.
[0530] 396. The method of any one of embodiments 318-395, wherein
the formulation elongates eyelash hairs by daily application over a
period of 60 days.
[0531] 397. The method of any one of embodiments 318-396, wherein
the formulation is applied by a multi-use applicator.
[0532] 398. The method of embodiment 318, wherein the alcohol is
ethanol, and the oil is a combination of castor oil and jojoba
oil.
[0533] 399. The method of embodiment 318, wherein the formulation
comprises about 0.02% w/v bimatoprost, about 1% v/v ethanol, about
3% v/v castor oil, about 71.6% v/v jojoba oil, about 24% v/v sweet
almond oil, and about 0.4% v/v Vitamin E.
[0534] 400. The method of embodiment 318, wherein the formulation
comprises 0.3% w/v bimatoprost, 7% v/v ethanol, 3% v/v castor oil,
64.5% v/v jojoba oil, 12% v/v olive oil, 12% sweet almond oil, 0.5%
v/v Rosemary oil, 0.5% v/v tea tree oil and 0.5% v/v Vitamin E.
[0535] 401. The method of embodiment 318, wherein the formulation
comprises 0.1% w/v bimatoprost, 3% v/v ethanol, 3% v/v castor oil,
68.5% v/v jojoba oil, 8% v/v avocado oil, 8% v/v olive oil, 8% v/v
sweet almond oil, 0.5% v/v rosemary oil, 0.5% v/v tea tree oil,
0.5% v/v Vitamin E.
[0536] 402. The method of embodiment 318, wherein the formulation
comprises 0.02%-0.03% w/v bimatoprost, about 1% v/v ethanol, about
3% v/v castor oil, and about 70-96% v/v jojoba oil.
[0537] 403. A method of relieving dry eye by applying a formulation
comprising at least one naturally occurring oil to the eyelid
margin, wherein the formulation is substantially free of water and
is free of preservatives.
[0538] 404. The method of embodiment 403, wherein the concentration
of the oil is from about 1% to about 99%.
[0539] 405. The method of embodiment 403, wherein the concentration
of the oil is from about 50% to about 99%.
[0540] 406. The method of embodiment 403, wherein the concentration
of the oil is from about 70% to about 99%.
[0541] 407. The method of embodiment 403, wherein the concentration
of the oil is from about 80% to about 99%.
[0542] 408. The method of embodiment 403, wherein the concentration
of the oil is from about 90% to about 99%.
[0543] 409. The method of embodiment 403, wherein the concentration
of the oil is from about 93% to about 99%.
[0544] 410. The method of embodiment 403, wherein the concentration
of the oil is from about 95% to about 99%.
[0545] 411. The method of embodiment 403, wherein the concentration
of the oil is from about 97% to about 99%.
[0546] 412. The method of embodiment 403, wherein the concentration
of the oil is from about 90% to about 97%.
[0547] 413. The method of embodiment 403, wherein the concentration
of the oil is from about 93% to about 98%.
[0548] 414. The method of any one of embodiments 403-413, where the
oil is linear or branched.
[0549] 415. The method of any one of embodiments 403-413, where the
oil is saturated or unsaturated.
[0550] 416. The method of any one of embodiments 403-413, where the
oil is substituted with one, two, or three substituents.
[0551] 417. The method of any one of embodiments 403-413, where the
oil is made up of 10 to 40 carbon atoms.
[0552] 418. The method of embodiment 403 where the formulation is
about 71.6% v/v jojoba oil, about 3% v/v castor oil, about 24% v/v
sweet almond oil, and about 0.4% Vitamin E.
[0553] 419. In one embodiment is a method of application whereby
the formulation of any of embodiments 1-205 is delivered to the
eyelid margin by a positive displacement device comprising a
reservoir attached to a roller ball, brush, or felt tip device.
[0554] 420. In one embodiment is a non-aqueous, non-preserved
formulation for stimulating hair growth, comprising an eicosanoid,
ethanol and an oil, wherein the eicosanoid is present in a
concentration of about 0.01%-0.3% w/v and ethanol is present in a
concentration of about 1%-7% v/v.
[0555] 421. The formulation of embodiment 420 wherein the
eicosanoid is bimatoprost and the oil is a plant oil.
[0556] 422. The formulation of embodiment 420 wherein the plant oil
is selected from the group consisting of lavendar essential oil,
cedar wood essential oil, thyme essential oil, clary sage essential
oil, rosemary essential oil, polygonum multiflorum, castor oil,
jojoba oil, avocado oil, olive oil, sweet almond oil, vitamin
E.
[0557] 423. The formulation of embodiment 421 or 422, wherein
formulation is for stimulating eyelash growth and comprises about
0.02-0.03% w/v bimatoprost.
[0558] 424. The formulation of embodiment 423 comprising about
0.03% w/v bimatoprost, about 1% v/v ethanol, about 3% v/v castor
oil and about 96% v/v jojoba oil.
[0559] 425. The formulation of embodiment 422 comprising about
0.02% w/v bimatoprost, about 1% v/v ethanol, about 3% v/v castor
oil, and about 71.6% v/v jojoba oil, about 24% v/v sweet almond
oil, and about 0.4% v/v vitamin E.
[0560] 426. The formulation of embodiment 421 or 422, wherein
formulation is for stimulating scalp growth and comprises about
0.01%-0.3% w/v bimatoprost.
[0561] 427. The formulation of embodiment 426 comprising 0.3% w/v
bimatoprost, 7% v/v ethanol, 3% v/v castor oil, 64.5% v/v jojoba
oil, 12% v/v olive oil, 12% sweet almond oil, 0.5% v/v Rosemary
oil, 0.5% v/v tea tree oil, 0.5% v/v Vitamin E.
[0562] 428. The formulation of embodiment 421 or 422, wherein
formulation is for stimulating eyebrow growth and comprises about
0.01%-0.3% w/v bimatoprost.
[0563] 429. The formulation of embodiment 428 comprising 0.1% w/v
bimatoprost, 3% v/v ethanol, 3% v/v castor oil, 68.5% v/v jojoba
oil, 8% v/v avocado oil, 8% v/v olive oil, 8% v/v sweet almond oil,
0.5% v/v rosemary oil, 0.5% v/v tea tree oil, 0.5% v/v Vitamin
E.
Example S
Example I
Bacterial and Mold Growth
[0564] Test: (0.03% Bimatoprost anhydrous formulation) of the
following 8 month old formulation:
0.03% w/v bimatoprost, 1% v/v ethanol, 3% v/v castor oil, and 96%
v/v jojoba oil (Formulation 3, Table 1) was swiped on Microslides
(LotionCraft, Cat # M-NUT/MAC)
Starting Date: Day 0
End Date: Day 10
[0565] Yellow side: tested for bacterial growth Pink side: tested
for yeast and molds
Procedure:
[0566] 1) Swipe 0.03% Bimatoprost anhydrous formulation on both
sides of pack #1 of Microslides, incubated for 10 days in room
temperature [0567] 2) Negative control: swipe 0.03% Bimatoprost
anhydrous formulation on both sides of pack #2 of Microslides, no
incubation, took picture immediately. [0568] 3) Positive control
for microbial growth: inoculated household microbes on both sides
of pack #3 of Microslides, incubated for two days when pictures
were taken. [0569] Observe for microbial growth every day and take
picture on Day 10 with controls. [0570] Results: photos on Day 10,
see FIG. 2.
[0571] Conclusion: no bacteria, yeast or mold was found on tested
0.03% Bimatoprost anhydrous formulation or the negative
control.
Example II
[0572] A 52-year old female with short and sparsely dense eyelashes
applied the Formulation 3 (Table I) consisting of 0.03% w/v
bimatoprost, 96% v/v jojoba oil, 3% v/v castor oil, 1% v/v ethanol
once daily to the upper eyelid margin. This was achieved by using a
pen-like cylindrical reservoir fitted with a felt/fiber tip (see
FIG. 1). The bimatoprost formulation was applied to the upper
eyelid margin by a single directed motion. Following 8 weeks of
daily treatment, the eyelashes increased in length by approximately
50% and the eyelash population was distinctly denser.
Example III
[0573] A 57-year old female with short and sparsely dense eyelashes
and eyebrows applied the Formulation 13 (Table 2) consisting of
0.02% w/v bimatoprost, 71.6% v/v jojoba oil, 24% v/v sweet almond
oil, 3% v/v castor oil, 1% v/v ethanol and 0.4% v/v vitamin E
("Formulation NoneA) once daily to the right upper eyelid margin
and to the left and right eyebrows. This was achieved by using a
pen-like cylindrical reservoir fitted with a felt/fiber tip (see
FIG. 1). As comparison, an aqueous eyelash growth product
("Formulation A") with 0.03% w/v bimatoprost currently on the
market was applied on the left upper eyelid margin according to the
product instruction. The eyelash became darker and longer after 123
days of daily bimatoprost treatment and the eyebrow became darker
and longer after 91 days of daily bimatoprost treatment (see FIG.
3). There was no obvious difference on eyelash growth between
"Formulation NoneA with 0.02% bimatoprost and Formulation A with
0.03% bimatoprost.
Example IV
[0574] A 45-year old female with normal length and dense eyelashes
applied the Formulation 13 (Table 2) consisting of 0.02% w/v
bimatoprost, 71.6% v/v jojoba oil, 24% v/v sweet almond oil, 3% v/v
castor oil, 1% v/v ethanol and 0.4% v/v vitamin E ("Formulation
NoneA) once daily to the right upper eyelid margin. This was
achieved by using a pen-like cylindrical reservoir fitted with a
felt/fiber tip (see FIG. 1). As comparison, an aqueous eyelash
growth product ("Formulation A") with 0.03% w/v bimatoprost
currently on the market was applied on the left upper eyelid margin
according to the product instruction. The eyelash became darker and
longer after 109 days of daily bimatoprost treatment (see FIG. 4).
There was no obvious difference on eyelash growth between
"Formulation NoneA with 0.02% bimatoprost and Formulation A with
0.03% bimatoprost.
Example V
[0575] A Caucasian female who has undergone chemotherapy
experiences hypotrichosis of the eyelashes. The patient applies
once daily the Formulation 13 (Table II) of 0.02% w/v bimatoprost,
1% v/v ethanol, 3% v/v castor oil, 71.6% v/v jojoba oil, 24% v/v
sweet almond oil, and 0.4% v/v Vitamin E. After 60 days of daily
application, the patient's eyelashes are thicker, longer and darker
than prior to treatment.
Example VI
[0576] A 32 year old Hispanic male suffers from alopecia areata and
begins losing hair. The patient applies once daily the Formulation
31 (Table IV) of 0.3% w/v bimatoprost, 7% v/v ethanol, 3% v/v
castor oil, 64.5% v/v jojoba oil, 12% v/v olive oil, 12% sweet
almond oil, 0.5% v/v Rosemary oil, 0.5% v/v tea tree oil, 0.5% v/v
Vitamin E. After applying the formulation the patient experiences
new hair growth on his scalp and his alopecia areata symptoms
improve.
Example VII
[0577] A 51 year old Caucasian female notices that her eyebrows are
thinning. The 51 year old Caucasian female applies the Formulation
25 (Table III) of 0.1% w/v bimatoprost, 3% v/v ethanol, 3% v/v
castor oil, 68.5% v/v jojoba oil, 8% v/v avocado oil, 8% v/v olive
oil, 8% v/v sweet almond oil, 0.5% v/v rosemary oil, 0.5% v/v tea
tree oil, 0.5% v/v Vitamin E. After 60 days of twice daily
application, the patient's eyebrow increase in density, length, are
thicker and denser.
Example VIII
[0578] An Asian female diagnosed with dry eye disease applies the
Formulation 3 (Table V) consisting of 0.03% w/v bimatoprost, 96%
v/v jojoba oil, 3% v/v castor oil, 1% v/v ethanol once daily to the
upper eyelid margin. This is achieved by using a pen-like
cylindrical reservoir fitted with a felt/fiber tip (see FIG. 1)
once daily before bed time. After 2-3 months daily use at night
before bed time on both eyes, the dry eye symptoms were relieved.
The dry eye symptoms came back on discontinuing use of the
formulation for a few months.
Example IX
[0579] An Asian female diagnosed with dry eye disease applied
formulation 34 of Table VI consisting of 71.6% v/v jojoba oil, 3%
v/v castor oil, 24% v/v sweet almond oil, 0.4% Vitamin E oil once
daily to the upper and lower eyelid margins. This was achieved by
using a pen-like cylindrical reservoir fitted with a felt/fiber tip
(see FIG. 1). After one month daily use at night before sleep on
both eyes, the user reported that the formulation provided relief
of symptoms associated with dry eye. Additionally, the user
reported that compared to eye drops, this method of treatment was
preferred due to the absence of any stinging sensation commonly
associated with application of eye drops. The user also reported a
superior level of relief of dry-eye symptoms as compared to a prior
course of therapy comprising an eye drop formulation containing
0.1% fluorometholone and eye drop formulation containing 0.1%
sodium hyaluronate [active: fluorometholone 0.1%. preservative:
benzalkonium chloride 0.004%. Inactives: edetate disodium;
polysorbate 80; polyvinyl alcohol 1.4%; purified water; sodium
chloride; sodium phosphate, dibasic; sodium phosphate, monobasic;
and sodium hydroxide to adjust pH. FML.RTM. suspension is
formulated with a pH from 6.2 to 7.5. It has an osmolality range of
290-350 mOsm/kg and active: sodium hyaluronate 0.1%. Inactives:
e-Aminocaproic acid, disodium edetate, benzalkonium chloride,
sodium chloride, potassium chloride, pH adjuster. pH from 6.0 to
7.0. Osmolality 0.9-1.1]
[0580] The patient reported a lack of stinging sensation
immediately after use, with no stinging sensation from the test
formulation. Additionally, the patient reported the eyes feel more
moisturized after using the test formulation.
Example X
[0581] A Caucasian female presenting with dry eye disease
symptomology applied formulation 34 of Table VI consisting of 71.6%
v/v jojoba oil, 3% v/v castor oil, 24% v/v sweet almond oil, 0.4%
Vitamin E oil once daily before bedtime to the upper eyelid
margins. This was achieved by using a pen-like cylindrical
reservoir fitted with a felt/fiber tip (see FIG. 1). This
formulation was described as providing relief of symptoms for 1-5
hours.
Example XI
[0582] A Caucasian female presenting with dry eye disease
symptomology applied formulation 34 of Table VI consisting of 71.6%
v/v jojoba oil, 3% v/v castor oil, 24% v/v sweet almond oil, 0.4%
Vitamin E oil once daily before sleep to the upper eyelid margins.
The female has experienced relief of symptoms for a few hours in a
day.
[0583] While preferred embodiments of the present invention have
been shown and described herein, it will be obvious to those
skilled in the art that such embodiments are provided by way of
example only. Numerous variations, changes, and substitutions will
now occur to those skilled in the art without departing from the
invention. It should be understood that various alternatives to the
embodiments of the invention described herein may be employed in
practicing the invention. It is intended that the following claims
define the scope of the invention and that methods and structures
within the scope of these claims and their equivalents be covered
thereby.
* * * * *