Note: Descriptions are shown in the official language in which they were submitted.
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METHOD OF TREATING ACNE WITH STRATUM CORNEUM PIERCING
DEVICE
BACKGROUND OF INVENTION
Devices have been used for the systemic delivering of
active substances through the skin which otherwise would
have to be administered intravenously. In particular,
transdermal delivery of actives (including patches that
deliver nicotine, scopolamine, nitroglycerin, estrogen, and
various pain relievers) are quite popular as they allow the
user to maintain a steady state of drug delivery. Devices
have also been used for single dose delivery or sampling of
biological fluids from barrier membranes (e.g., skin).
Such devices include those that pierce the skin, thereby
disrupting the barrier that the skin provides. In such a
puncture-type system, a needle may also be used to deliver
systemic drugs into or below the layers of the skin.
Examples of these delivery systems are disclosed in U.S.
Patent Nos. 5,879,326, 6,132,755, and 6,743,211.
The present invention provides for devices and/or the
use of the devices, for example for the treatment of skin
disorders, such as acne.
ST.TNIINARY OF THE INVENTION
In one aspect, the present invention features a method
of treating a skin disorder with a device. In one"
embodiment, the device includes (i) a microprotrusion
member having a skin-contacting surface, and plurality of
stratum corneum-piercing microprotrusions thereon and (ii)
a composition for treatment of the skin disorder, wherein
the method includes piercing the stratum corneum of the
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skin with the microprotrusion member and applying the
composition from the device to the skin.
In one aspect, the invention features a method of
treating acne by piercing the stratum corneum of skin in
need of such treatment with a stratum corneum-piercing
device including a microprotrusion member having a skin-
contacting surface and plurality of stratum corneum-
piercing microprotrusions thereon.
In one aspect, the present invention features a method
of removing pus from a pimple by piercing the pimple with a
stratum corneum-piercing device, the device including a
microprotrueion member having a skin-contacting surface and
plurality of stratum corneum-piercing microprotrusions
thereon.
In one aspect, the present invention features a device
including (i) a microprotrusion member having a skin-
contacting surface and plurality of stratum corneum-
piercing microprotrusions thereon and (ii) a composition
including an active agent (such as an anti-acne agent, a
depigmentation agent, an anti-aging agent, a scar-reducing
agent, an anti-inflammatory agent, an antimicrobial agent,
an antioxidant, an immunosuppressive agent, an
immunostimulant agent, a hair-growth enhancing agent, a
hair growth retarding, a wound healing agent, an
anesthetic, an analgesic, or a botulinum toxin).
In one aspect, the present invention featur-es a
stratum corneum-piercing device including a mi=croprotrusion
member having a skin-contacting surface and plurality of
stratum corneum piercing microprotrusions thereon, the
device being adapted to move the microprotrusion member
lateral to the surface of the skin surfa=ce upon contact
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with the skin. Examples of lateral movement include, but
are not limited to, linear and rotational motion.
In one aspec, t, the present invention featur-es a method
of treating acne by piercing the stratum corneum of skin in
need of such treatment with a stratum corneum-piercing
device that contains at least one stratum corneum-piercing-
microprotrusion and a compressible cover such that the
compressible cover substantially encases the at least one
stratum corneum-piercing microprotrusion, wherein upon
contacting the skin with the compressible cover, the at
least one stratum corneum-piercing microprotrusion
protrudes from said compressible cover and pierces said
stratum corneum of the skin.
In one aspect,'the present invention features a method
of removing pus from a pimple by piercing the pimple with a
stratum corneum-piercing device that contains at least one
stratum corneum-piercing microprotrusion and a compressible
cover such that the compressible cover substantially
encases the at least one stratum corneum-piercing
microprotrusion, wherein uponconta=cting the pimple with
the compressible cover, the at least one stratum corneum-
piercing microprotrusion protrudes from the compressible
cover and pierces the pimple and the compressible cover
absorbs said pus released from the pimple.
Other aspects, features, and advantages of the present
invention will be apparent from the detailed description of
the invention and from the claims.
DETAILED DESCRIPTION OF THE DRAWINGS
FIG. 1 is an enlarged perspective view of the skin
proximal side of a microprotrusion member useful in the
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present invention;
FIG. 2 is a partial top plan view of a microprotrusion
member of FIG. 1, before bending/punching the
microprotrusibns out of the plane of the sheet;
FIG. 3.~s a plan view of an implement having a convex
skin-contacting surface useful,in the present invention;
FIG. 4,is a cross sectional view of the implement
shown in FIG. 3;
FIG. 5 is a plan view of another embodiment of an
implement useful in the present invention;
FIG. 6 is a perspective view of another embodiment of
an implement useful in the present invention;
FIG. 7 is a cross-sectional view of the implement
shown in FIG. 6;
FIG. 8a is a top view of a patch device of the pres.ent
invention;
FIG. 8b is a cross-section view of a patch device of
the present invention;
FIG. 9 is a plan view of the microprotrusion member
shown in FIG. 7;
FIG. 10 is a cross-sectional view of the
microprotrusion member shown in FIG. 9;
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FIG. 11 is a partial view of the microprotrusion
member of FIGS. 5-10;
FIG. 12 is an elevated view of one embodiment of the
device of the present invention;
FIG: 13 is an elevated view of one'embodiment of the
device of the present invention;
Fig. 14 is an elevated view of another embodiment of
the device of the present invention;
FIG. 15 is a partial view of the microprotrusion
member of FIG. 14; and
FIG. 16 is a partial view of the microprotrusion
member of FIG. 14.
DETAILED DESCRIPTION OF THE INVENTION
It is believed that one skilled in the art can, based
upon the description herein, utilize the present invention
to its fullest extent. The following specific embodiments
can be construed as merely illustrative, and not limitative
of the remainder of the disclosure in any way whatsoever.
Unless defined otherwise, all technical and scientific
terms used herein have the same meaning as commonly
understood by one of ordinary skill in the art to which the
invention belongs. Also, all publications, patent
applications, patents, and other references menti-oned
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herein are incorporated by reference. As used herein, all
percentages are by weight unless otherwise specified.
In one embodiment, the present invention is directed
to a device and the use of that device for treating skin
disorders, suth as acne, scars, or visible skin
discolorations. The treatment involves disrupting the
stratum corneum of the skin and may or may not further
include the application of a composition that permeates
into the disrupted skin. A benefit of such a treatment
includes localizing the treatment to a certain area of skin
in need of such treatment.
Definitions
What is meant by a "product" is a product in finished
packaged form. In one embodiment, the package is a
container such as=a plastic or cardboard box for storing
such device and/or kit. In one embodiment, the product
contains instructions directing the user to apply the
microprotrusipn member to the skin (e.g., for the treatment
of a skin disorder).
What is meant by "promoting" is promoting,
advertising, or marketing. Exampl-es of promoting include,
but are not limited to, written, visual, or verbal
statements made on the product or in stores, magazines,
newspaper, radio, television, internet, and the like. For
promoting the treatment of the skin disorder acne, examples
of such statements include, but are not limited to, "treats
acne," "safely pops pimples," "eliminates acne and/or
pimples/blemishes", and "visibly reduces the symptoms
and/or appearance of pimples." Similar statements can be
made for other skin disorders.
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As used herein, "administering to the skin in need of
such treatment" means contacting (e.g., by use of the hands
or an applicator)'the area of skin in need such treatment.
These features may be present on the face, such as under or
adjacent the eyes, nose, forehead, cheeks, jawls, and neck,
as well as other areas of the body such as the arms, chest,
back, shoulder, belly (e.g., stretch marks), and legs
(e.g., cellulite).
The term "treating" or "tr.eatment" of a skin disorder
means the treatment (e.g., complete or partial alleviation
or elimination of symptoms and/or cure) and/or prevention
or inhibition of the skin disorder.
As used herein, "composition" means a composition
suitable for admini'stration to the skin.
As used herein, "cosmetically-acceptable" means that
the ingredients or compositions which the term describes
are suitable for use in contact with the skin without undue
toxicity, incompatibility, instability, irritation,
allergic response, and the like. This term is not'intended
to limit the ingredient/composition to which it describes
for use solely as a cosmetic (e.g., the
ingredient/composition may be a pharmaceutical agent).
As used herein, "safe and effective amount" means an
amount of the active agent, compound, carrier, or of the
Composition sufficient to induce the desired effect, but
low enough to,avoid serious side effects. The safe and
effective amount of the compounds or composition will vary
with the area,being treated, the age, health and
skin/tissue type of the end user, the duration and nature
of the treatment, the specific compound or composition
employed, the particular cosmetically-acceptable carrier
utilized, and like factors.
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Skin Disorder
As used herein, the term "skin disorder" shall mean a
disease, disorder, or defect of tho skin including, but not
limited to, acne (including but not limited to acne
vulgaris and acne rosacea), psoriasis, infections,
blemishes, hyperpigmentation (including but not limited to
post inflammatory hyper-pigmentation (PIH)),
hypopigmentation, hair growth disorders such as alopecia
and excessiv'e or unwanted hair growth, rough skin, dry
skin, lax skin (including but not limited to skin lacking
in firmness'or elasticity), wrinkles (including but not
limited to fine lines and course wrinkles),
hypervasculatated skin (including but not limited to dark
circles), sebum production disorders (e.g., skin shine),
excessive pore appearance, excessive perspiration
(including hyperhidrosis), tattoo appearance, rashes
(including allergic and diaper), scar appearance, pain,
itch, burn, inflammation, warts, corns, calluses, edema,
poison ivy/oak, skin cancer, and bites from insects,
spiders, snake, and other animals.
Examples of skin infections include, but are not
limited to, acne, impetigo, folliculitis, furun=culosis,
ecthyma, eczema, psoriasis, atopic dermatitis,
epidermolysis bullosa, icthyosis, infected traumatic
lesions (e.g., ulcers, minor burns, cuts, abrasions,
lacerations, wounds, biopsy sites, surgical incisions and
insect bites, which have become infected), herpes (e.g.,
cold sores) or other bacterial or viral infections. The
device may be used to help remove devitalized and/or
contaminated bodily fluid from wounds.
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Examples of wrinkled skin include, but are not limited
to, fine lines, deep-set wrinkles, laugh lines, crows feet,
stretch marks, cellulite, and frown lines.
Examples of discolored skin include but are not
limited to hyperpigmented skin, hypopigmented skin,
blemished skin, bruised, and hypervaculated skin.
Examples of hyperpigmented skin include, but are not
limited to, freckles, age spots (sloar lentigo), sun spots,
melasma, sallow color, dyschromia, post-inflammatory
pigmentation (PIH), and other discolored skin.
An example of hypopigmented skin includes, but is not
limited to, vitiligo.
Examples of blemished skin include, but are not
limited to, pustules, comedones, pimples, blackheads or
other types of eruptions associated with acne.
Examples of scar skin disorder include, but are not
limited to scars from acne, surgery, insect bite, burns,
injuries, trauma, and other wounds.
Mucosal Disorders
The devices herein may also be used to treat disorders
of mucosal membranes (e.g., the mucosal membranes of the
mouth, and vagina). Example of mucosal disorders include,
but are not limited to, periodontal diseases, gum diseases,
oral/pharyngeal cancer, candida infection, herpes simplex
or other virus infection that causes oral herpes such as
cold sores and fever blisters, and genital herpes such as
genital sores,.
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Stratum Corneum-piercing Device
In one embodiment, the stratum corneum-piercing device
includes a mitroprotrusion member having a skin-contacting
surface and plurality of stratum corneum piercing
microprotrus.ions thereon. The device may also include one
or more reservoirs.
In one embodiment, the corneum-piercing device
includes at,least one stratum corneum-piercing
microprotrusion and a compressible cover such that the
compressible cover, substantially encases said at least one
stratum corneum-piercing microprotrusion.
Microprotrusions
The term "microprotrusion" as used herein refers to a
stratum corneum piercing element that is adapted to
penetrate in the stratum corneum.' Microprotrusions
typically having a length of from about 20 to about 1000
microns, and preferably from about 50 to about 500 microns,
and more preferably from about 100 to about 250 microns.
What is meant by length is the length of the
microprotrusion adapted to penetrate into the skin (e.g.,
the length measured from the top of the microprotrusion to
the skin-contacting surface or other affixed to the skin
contracting surface such as an absorbent reservoir or the
compressed compressible cover). The average longest
diameter (e.g., the width of the microblade or the diameter
of a microneedle) measured along the length of the
microprotrusions are typically less than half of the length
of the microprotrusions, such as less than one quarter of
the length of the microprotrusions. In one embodiment, the
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average diameter of the.microprotrusions along it-s length
are from about 5 to about 500 microns, preferably from
about 10 to about' 250 microns, and more preferably from
about 25 to about 150 mi.crons. In one embodiment, the
microprotrusions are adapted to penetrate other sections of
the epidermis, but are not adapted to penetrate the dermis.
However, for certain applications such as treating scars,
cellulite, stretch marks, and wrinkles, the
microprotrusions may be adapted to penetrate into
superficial portions of the dermis.
The microprotrusions may be formed in different
shapes, such as needles, hollow needles, blades, pinsõ
punches, and combinations thereof. Tt is not n.ecessary that
the microprotrusioris on the device be made of a uniform
size (e.g., different lengths or average diameters) or
shape. what is meant by the term "blade" or "microblade"
is a microprotrusion that has at least one edge. The
microblade, optionally, may have a barb.
The term "microprotrusion array" as used herein refers
to a plurality of microprotrusions arranged in an array for
piercing the stratum corneum. An array of microprotrusions
can include a mixture of microprotrusions having, for
example, various lengths, outer diameters, inner diameters,
cross-sectional shapes, and spacing between the
microprotrusions. In one embodiment, microprotrusion array
includes hollow needles, for example hollow needles adapted
to inject a composition into the skin or remove fluids from
the skin.
In one embodiment, the microprotrusion member includes
from about 2 to about 5000 microprotrusions, such as from
about 10 to about 500 microprotrusions, such as from about
25 to about 200 microprotrusions, such as from about 3 to
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about 250 microprotrusions. In one embodiment, the
microprotrusion member has a microprotrusion density of
from about 1 microprotrusions /cm2 to about 2000
microprotrusions /cm2, such as from about 100
microprotrusibns /cm2 to about 1000 microprotrusions /cm2.
Examples of microprotrusion arrays and methods of
making sameare described in U.S. Patent Nos. 5,879,326,
3,814,097, 5,279,544, 5,250,023, 3,964,482, and Re. 25,637,
and PCT Publication Nos. WO 96/37155, WO 96/37256, WO
96/17648, WO 97/03718, Wo 98/11937, Wo 98/00193, Wo
97/48440, Wo 97/48441, WO 97/48442, Wo 98/00193, w0
99/64580, WO 98/28,037, and Wo 98/29365. Examples of such
methods of manufacture include, but are not limited to,
chemical vapor deposition, mechanic drawing or machining,
laser machining, molding, and photolithographic processes.
The microprotrusions can be constructed from a variety
of materials that have sufficient strength and
manufacturability to produce elements capable of piercing
the stratum corneum, such as, glasses, silicons, ceramics,
metals, metal alloys, semiconductors, inorganic crystals,
organic crystals, polymers, polymer composites, and
mixtures or composites thereof.
Examples of metals and metal alloys include, but are
not limited to, stainless steel, gold, iron, steel, tin,
zinc, copper, platinum, aluminum, germanium, zirconium,
titanium and titanium alloys containing molybdenum and
chromium, metals or non-metals plated with, gold, rhodium,
iridium, titanium, platinum, silver, silver halides, and
alloys of these or'other metals.
In one embodiment, the microprotrusions are made of
piezoelectric material that can change the dimension of the
microprotrusion corresponding to applied electricity, sucb.
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as a piezo-ceramic substance. Such manufacture, in one.
embodiment, would allow motion of the microprotrusions when
an electrical current waveform was supplied to piezo-
ceramic substance, thereby increasing the disruption of the
stratum-corneum. The electricity supplied to the disrupted
area may also accelerate healing and other benefits.
In one embodiment, the microprotrusions are made of a
shape memory metal, such as Nitinol, that can change the
dimension of the microprotrusion corresponding.to
temperature change. In one embodiment, the microprotrusion
member containing Nitinol is heat-treated and fabricated
into a first shape, such as shown in Figure 1. The
microprotrusion member is then be distorted into another
shape, such as the'shape as shown in Figure 2 (e.g., for
easy storage and/or protection of the microprotrusions).
During use, an increase in the device temperature (e.g.,
from the body temperature upon contact) will restore the
microprotrusion,member back to its first shape. The use of
a Nitinol metal alloy can also be used to generate motion
of microprotrusions (e.g., into and/or lateral to the
skin). Examples of inorganic and organic crystals include
diamond, aluminum oxide, soluble or insoluble salt
crystals, and quartz.
Examples of glasses include, but are not limited.to,
devitrified glass such as "Photoceram" availabl-e from
Corning in Cotning, N.Y.
Examples of rigid polymers include, but are not
limited to, natural polymers and synthetic polymers, such
as polystyre4e, polycarbonate, polytetrafluoroethylene,
polydivinyl fluoride, polypropylene, polyethylene,
"Bakelite", cellulose and cellulose acetate,
ethylcellulose, styrene/acrylonitrile copolymers,
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styrenebutadiene copolymers,
acrylonitrile/butadiene/styrene (ABS) copolymers, polyvinyl
chloride and acrylic acid polymers including polyacrylates
and polymethacrylates, and composites thereof. Examples of
microprotrusions containing such rigid pblymers are
disclosed in US Patent No. 6,881,203.
In one embodiment, the microprotrusions are made of a
biodegradable/bioabsorbable polymer. In such an
embodiment, if the microprotrusion, or portions thereof,
break off in'the skin, they will biodegrade. In a further
embodiment, the microprotrusion includes an active agent.
Representative biodegradable polymers include, but are not
limited to, polymers of hydroxy acids such as lactic acid
and/or glycolic acid such as polylactide, polyglycolide,
and polylactide-co-glycolide, polyanhydrides,
poly(ortho)esters,' polyurethanes, poly(butyric acid),
poly(valeric acid), poly(lactide-co-caprolactone), and
cyclic olefin copolymers. Representative non-biodegradable
polymers include polycarbonate, polymethacrylic acid,
ethylenevinyl acetate, polytetrafluoroethyl=ene, and
polyesters. Other examples include microprotrusions made of
a material that is capable of disintegration and dispersion
into the skin such as sugars, as described in US Patent
Application No. 2005/0065463.
In one embodiment, the microprotrusions are formed of
a nonporous solid or a porous solid (with or without a
sealed coating or exterior portion), and may be hollow. As
used herein, the term-"porous" means having pores =or voids
throughout at least a portion of the microprotrusion
structure, sufficiently large and sufficiently
interconnected to permit passage of fluid and/or solid
materials through the microprotrusion. As used herein, the
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term "hollow" means having one or more bores or channels
(e.g., substantially annular bores) through the interior of
the microneedle or microprotrusion structure, having a
diameter sufficiently large to~permit passage of fluid
and/or solid materials through the microneedle/
microprotrusion. The bores may extend throughout all or a
portion of the needle in the direction of the tip to the
base, extending parallel to the direction of the needle or
branching or exiting at a side of the needle, as
appropriate. The base surface that the microprotrusions
are attached to, or integral to, may also provide one or
more openings.
In one embodiment, the stratum-corneum piercing device
has at least one solid microprotrusion and one hollow
microprotrusion. This arrangement allows for positive
displacement of material, such as pus, from the treatment
site (e.g., as the microprotrusions penetrate the stratum
corneum, the hol'low microprotrusion accepts and removes
material displaced by (i) the solid microprotrusion, (ii)
the pressure of the device, and/or (iii) the added
composition from the device and/or as a result of reduced
pressure).
In one embodiment, the microprotrusion member has at
least one hollow microprotrusion utilized for delivering a
composition to the treatment site and at least one hollow
microprotrusibn (e.g., to remove bodily fluids, such as
pus).
The microneedle/microprotrusion can have substantially
straight or substantially tapered shafts. A hollow
microneedle that has a substantially uniform diameter,
which needle does not taper to a point, is refer=red to
herein as a "microtube." In one embodiment, the diameter
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of the microprotrusion is greatest at the base end of the
.microprotrusion and tapers to a point at the end distal the
base. The microprotrusion can also be fabricated to have a
shaft that includes both a substantially straight (e.g.,
untapered) portion and a substantially tapered portion.
The microprotrusions can be formed with shafts that
have a circu.lar cross-section in the perpendicular, or the
cross-section can be non-circular. For example, the cross-
section of the microprotrusion can be polygonal (e.g. star-
shaped, squate, triangular, rectangular), oblong, or
another shape. In one embodiment, the shaft has one or more
bores.
The microprotrusions can be oriented substantially
perpendicular or at an angle to the skin-contacting
surface. Preferably, the microprotrusions are oriented
substantially perpendicular to the skin-contacting surface
so that a larger density of microprotrusions per unit area
of skin-contacting surface is provided. An array of
microprotrusions can include a mixture of microprotrusi-on
orientations, heights, or other parameters.
Generally, the microprotrusions should have the
mechanical strength to resist distortion (such as bending)
while being inserted into the skin and while being removed.
In one embodiment, the microprotrusion is inserted into the
skin a single time. In another embodiment, the
microprotrusion is inserted into the skin multiple times at
the same or at different sites. In one embodiment, the
microprotrusion is hollow and should remain intact for
delivery of active agents, or for collection of bodily
fluids.
An example of a microprotrusion member having a skin-
contacting surface and a plurality of microprotrusions is
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shown in Figures 1 and 2. Looking at FIG. 1,
microprotrusion member 2 includes a plurality of
microprotrusions 4 (i.e., a microprotrusion array)
extending from one surface of a skin-contacting surface 6
(FIG. 1 shows microprotrusion member 2 is in an inverted
position to show the microprotrusions). The
microprotrusions 4 penetrate the stratum corneum of the
epidermis when pressure is applied to the device (i.e., the
skin of an animal and particularly a human).
The microprotrusions 4 may be formed from a single
piece of material (see Fig. 2, which shows the one pi-ece
construction prior to the bending of the microprotrusions
out of the plane of the sheet) or separately joined to a
skin-contacting surface by any manufacturing method (not
shown).
In one embodiment, the microprotrusions 4 and the
skin-contacting surface 6 are essentially impermeable or
are impermeable~to the passage of an agent. In one
embodiment, the skin-contacting surface 6 is formed with a
multiplicity of openings 8 between the microprotrusions 4
for enhancing the movement of an agent or composition there
through (e.g., the composition is delivered into the skin
from the microprotrusion member through the holes in the
stratum corneum which are made by the microprotrusions 4).
In one embodiment where the device is used to treat
acne, when tho microprotrusion member forms holes in the
pimple or affected area, body fluids, such.as pus, may be
loosened and/or withdrawn into a reservoir of the
microprotrusi,on member through the perforations formed in
the stratum corneum and through the openings in the skin-
contacting surface. Similarly, the device of the present
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invention may be used to facilitate the outward flow of
wound exudates thus enhancing wound healing.
In one embodiment, the opening 8 corresponds to the
portion of the skin-contacting surface 6 occupied by each
of the microprotrusions 4 prior to the microprotrusions 4
being transpositioned into the downward depending position.
The number of microprotrusions 4 per opening 8 can be any
number, preferably however from about 1 to about 30
microprotrusions per opening and more preferable from about
1 to about 4 microprotrusions per opening. Furthermore, the
number of openings 8 per microprotrusion member 2 and the
number of microprotrusions per microprotrusion member 2 are
independent.
In the embodiment shown in FIG. 1, the
microprotrusions 4 have an average thickness ("t") along
the length ("1") of the microprotrusion, which is much
smaller than the average width ("w") along the length of
the microprotrusion.
In one embodiment, the skin site is pre-treated with
compositions, such as topical anesthetic, antiseptic
cleansing, skin softening agents.
In one embodiment, the skin site is pretreated with a
one or more energy sources such as light, electric,
magnetic, electromagnetic, acoustic (such as ultrasound),
thermal, or mechanical energies. Such pretreatment can
function to (i) condition the skin site for an optimized
microprotrsusion application (e.g. via skin softening by
heat treatment, where heat can be generated by chemical
(e.g. redox reactions), physical (e.g. radio-frequency
current, electricity, light, electro-magnetic, infrared
(IR)), physico-chemical (e.g. salvation, heat released from
phase transition processes), (ii) enhance the treatment
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efficacy of the skin site (e.g., via improved active
delivery to the target site) and/or (iii) exert energy
stimulation on the target site and its surroundingtissue
and increase blood microcirculation.
In one embodiment, the target site is post-treated
with one or mor-e energy sources such as light, electric,
magnetic, electromagnetic (e.g., PCT Patent Application WO
98/55035 for pulsed electromagnetic radiation/energy, US
Patent No. 6,835,202 for narrow spectral band light source,
and US Patent No. 5,720,894 for laser light), acoustic
(such as ultrasound), thermal, and/or mechanical energies.
One particular benefit to use post-energy treatment is the
delivery of energy deeper into the skin to the target site
e.g. sebum gland in acne treatment, sweat gland for
hyperhidrosis treatment via the microchannels created by
microprotrusions. Such post-treatment functions to enhance
the treatment efficacy via (i) exerting energy stimulation
on the target s.ite and its surrounding tissue and increase
blood microcirculation, (ii) use energy means to help
reducing microbial loads (e.g. blue light to kill P. acnes
in pimples), (iii) improving active agent delivery, and/or
(iv) adding additional in-situ actives (e.g. Ag/AgCl-zinc
galvanic electric electrodes in contact with the target
site under moist condition to generate both electric
stimulation and in-situ zinc ions into skin site).
Skin-contacting Surface
The skin-contacting'surface of the microprotrusion
member can also be constructed from a variety of materials,
including, but not limited to, metals, ceramics,
semiconductors, organics, polymers, plastics, and
composites thereof. The skin-contacting surface includes
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the base to which the microprotrusions are attached or
integrally formed. A reservoir may also be attached to the
skin-contacting surface. In one embodiment, the skin-
contacting surface has at least one opening to allow (i) a
composition to move from a reservoir, through the opening,
.and onto the skin and/or (ii) bodily fluid to move from the
skin, through the opening, and into a reservoir. In one
embodiment, the skin-contacting surface forms a stop and
help control how deep the microprotrusions can penetrate
the skin.
In one embodiment of the device, the skin-contacting
surface is formed from a thin, rigid material that is
sufficiently stiff so as to force the attached
microprotrusions through the skin in such areas where the
skin resists deformation by the microprotrusions, such as
those materials used to form the microprotrusions.
Examples include but are not limited to, glasses, silicons,
ceramics, metals, metal alloys, semiconductors, inorganic
crystals, organic crystals, polymers, polymer composites,
and mixtures or composites thereof.
In another embodiment, the skin-contacting surface is
formed from flexible materials to allow the device to fit
the contours of the skin and to adapt to deformations that
may occur when the microprotrusions are applied. A flexible
surface further facilitates more consistent penetration
during use, since penetration can be limited by deviations
in the attachment surface. For example, the surface of
human skin is not flat due to dermatoglyphics, e.g.,
wrinkles, scars, pimples, and hair, and is highly
deformable. The flexible skin-contacting surface can be
deformed mechanically (for example, using an actuator or
other pressure) in order to pierce the skin.
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The size of the skin-contacting surface will depend on
the area of the skin disorder being treated., Inone
embodiment, the area of the skin-contacting surface is from -
about 0.05 cm2 to about 500 cm2, such as from about 0.1 cm2
to about 100 cm2. In one embodiment, the total surface area
of the one or more openings-from about 1 to about 95
percent of the total surface area of the skin-contacting
surface (e.g., including the surface area of the
opening(s)), such as from about 50 to about 80 percent.
Compressible Cover
In one embodiment, the stratum-corneum piercing device
comprises a compressible cover such that the compressible
cover substantially encases said at least one stratum
corneum-piercing microprotrusion. In one embodiment, the
device is fabricated such that upon contacting the skin
with said compre'ssible cover, the at least one stratum
corneum-piercing microprotrusion protrudes from the
compressible cover and pierces the stratum corneum of the
skin. In one embodiment, at least 20 microns (such as at
least 100 microns) of the at least one microprotrusion
protrudes from the compressible cover upon application of
the compressible cover against the skin with less than
about fifteen lbs/cm2 of force, such as less than about five
lbs/cm2 of force.
What is meant by "compressible" is the material has
either elasticity, plasticity and/or deformability such
that under anexternal force, the material can change its
geometric shape. In one embodiment, the thickness of the
compressible material will compress by at least 25 percent
upon application of a force of less than about fifteen
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lbs/cm2 of force, such as less,than about five lbs/cm? of
force. The material may following compression either
completely or partially regain its original geometry.
What is meant by "substantially encases" is that the
cover conceals at least 75%, preferably at least 90% or
more preferably 100%, of the length of the at least one
stratum corrieum-piercing microprotrusion.
The compressible cover provides a cover for the
microprotrusion(s). Benefits of having a cover over the
microprotrusion(s) include (i) protection against
accidental pricking (e.g., to protect user against
infection risk), ('ii) provide anesthetic appearance of the
device and the reduction of fear of use, (iii) providing a
means to keep the microprotrusion relatively clean or =even
sterile prior to use, (iv) providing a cushion that may aid
in comfort when the device is being used, (v) provide
stability for the microprotrusion as it enters the tissue,
and/or(vi) provide a close contact or seal to enable the
easy application of microprotrusions.
In one embodiment, the compressible cover is absorbent
such that it can store a composition (e.g., containing an
active agent) and/or collect bodily fluids such as pus. In
one embodiment, the absorbent material is capable of
absorbing liquids in an amount of at least 25 percent of
its weight. Examples of absorbent, compressible materials
include, but are not limited to; woven and nonwoven
materials, hydrogels, hydrocolloids, silicone rubbers,
celluloses (e.g., cotton and rayon or their derivatives),
wool, polyamides (e.g., nylon), and silk.
In one embodiment, the compressible cover is made
completely or partially from a porous absorbent material or
non-absorbent material. Examples of porous materials
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include but not limited to the viscoelastic foam material
such as polyurethane, or other material such as plasticized
PVC.
In one embodiment, the compressible cover is non-
absorbent. Examples of non-absorbent, compressible
materials include, but are not limited to, solvent
resistant silicone rubbers (such as fluorosilicones and
organic (butyl) rubbers), natural or synthetic rubbers or
elastomers such as made from acrylic elastomers, styrene-
butadiene rubber, butyl rubber, low density polyethylene,
polyisoprorene, ethylene-acrylic elastomers, ethylene-
propylene-diene rubber, ethylene-vinyl acetate copolymer,
fluorocarbon elatomers, silicone rubber or silicone
elastomers, nitrile rubber, polybutadiene, polyethers,
thermoplastic elastomers polyurethane, latexes, and
plasticized polyvinyl chloride (PVC), ,and their composites.
other compressible materials can include viscoelastic
memory foam materials made from polyurethane and certain
chemicals.
In one embodiment, the compressible cover is made from
a combination of absorbent and non-absorbent materials.
In one embodiment, the compressible cover further
encases a reservoir that contains a composition that is
expelled from the reservoir upon puncture of the
compressible cover by the microprotrusion(s). In one
embodiment, the composition contains an anti-acne active.
In one embodiment, the device contains an active agent
(such as a drug) for the'local or systemic administration
(e.g., a vacoine).
In one embodiment, a composition containing an active
agent in the compressible cover is deliv.er-ed to the skin in
need of such treatment. The device may be packaged such
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that a composition is (i). added to the compressible cover
proximate to use or (ii) contained within=the compressible
cover during storage.
Reservoir
In one embodiment, the device disclosed herein also
includes one"'or more reservoirs for containing one or more
compositions and/or collecting body fluids, such as pus or
wound extrudate, from the skin.
In one embodiment, the reservoir is in communication
with the microprotrusion member. In one embodiment, the
reservoir is attached by an adhesive (such as cyanoacrylate
glue) to the side of the skin-contacting surface opposite
the side including-the microprotrusions. A seal lining may
also be included to secure the holding of the fluid
collected.
The reservoir may be in the form of a chamber enclosed
with rigid or flexible walls or in the form of a absorbent
substrate such as a nonwoven fabric, a hydrogel, or
hydrocolloid pad (e.g., in a bandage-like device with
backing layer). The rigid polymer materials that may be
used to manufacture the rigid reservoir include but are not
limited to natural polymers and synthetic polymers, such as
polystyrene, acrylonitrile/butadiene/styrene (ABS)
copolymers polymethylmethacrylate, polytetrafluoroethylene,
polycarbide, nylon, and polycarbonate. The flexible
polymers, that may be used to manufacture the flexible
polymer reservoir enclosure include but are not limited to
as polyethylene, polypropylene, polyurethane, thermoplastic
elastomers, silicones, latexes, rubbers, and polyvinyl
chloride. Absorbent materials include, but are not limited
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to, woven and nonwoven materials, hydrogels, and
hydrocolloids. ,
A composition containing benefit agents may be stored
in the reservoir prior to administering to the skin. The
reservoir may be.a pouch, a small bag, a unit-dose
container with any shape and size. It may be squeezable to
dispense the composition to the skin before, during or
after the microprotrusion application. The reservoir may
also be connected to a vacuum mechanism, or be able to
create a vacuum environment, in order to extract body waste
to extract pus from a pimple. See, e.g., U.S. Patent No.
6,562,014.
In one embodiment, microprotrusion arrays are attached
to an extraction device, as described in U.S. Patent No.
6,562,014 and may be applied to treat pimples or extract
the pus from pimples filled with pus (pustule). The
plunger of the extractor device is pulled out first and
then, the device is placed on the treated skin site. Using
the thumb, the plunger is pushed in all the way until the
microprotrusions pierce the stratum corneum and a suction
action is activated to remove the pus. 'In one embodiment,
a vacuum in the range of from about 0.1 to about 0.99 atm
(such as 0.2 to 0.8 atm) is applied to create plural
microchannels. A seal film or liner made from, for example
polyurethane, may be added to the extractor opening end to
maintain the vacuum. Optionally, a disposable absorbent
material made from e.g. cellulose, or nonwoven material, is
added behind the microprotrusion disk to collect pus waste
from the pimple. Optionally, a topical composition may be
applied to the treated site at this.point.
In one embodiment, the reservoir may contain an
absorbent material such as sodium carboxymethyl cellulose
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adhesive, a hydrogel, cotton,, porous foam, or a nonwoven
fabric.
Patch
In one embodiment, the microprotrusion member in
Figure 1 may be fabricated into an adhesive patch device
that resembl'es a bandage or transdermal patch. In one
embodiment, the adhesive patch device 800 (Figures 8a and
8b) has a multi-layered device structure: the top layer is
the microprotrusion member 810, the second layer is the
absorbent layer 820, and the third layer is the backing
layer 830. Figure'8b shows a cross s.ectional view of the
device of Figure 8a taken along lines 801.
The absorbent layer 820 may be replaced with a non-
absorbent layer, which can be made of rigid or flexible
materials. In one embodiment, absorbent layer 820 contains
a reservoir 5 that contains a composition to be dispensed
through the microprotrusion member 810. Reservoir 850 may
be made from an individual or multiple chambers.
In one embodiment, there is an adhesive coating at the
periphery edge of backing layer 830 in order to affix the
patch to the skin of a user (e.g., similar to an island-
type bandage design). Alternatively, if the absorbent layer
820 is adhesive hydrogel or hydrocolloid layer, the patch
may not require such additional adhesive for skin
attachment. In one embodiment, the device 800 includes a
release liner layer to cover the device 800 prior to use
(not shown). In one embodiment, the absorbent layer 820.in
the patch devipe is used to extract bodily fluids (such as
pus from a pimple) after the microprotrusion member of the
device pierces the stratum corneum. In one embodiment, a
composition in the absorbent layer (or coated on the
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microprotrusion members) is delivered into the diseased-
skin after the microprotrusion member.pierces the stratum
corneum.
The patch device can be seal,ed in a package during
storage. The sealed patch can be sterilized, e.g., by gamma
irradiation with a minimum of 25 kGy irradiation per dose..
The sealed package may assist the device in remaining
sterile and stable by blocking microbiologic pathogens,
moisture, oxygen, W rays, and/or other harmful elements.
In one embodiment, the patch is left on the skin for
an extended period of time to deliver the active agent
and/or composition into skin or to extract bodily fluids
from the treatment site. In one embodiment, the patch is.
left on the skin for an extended period of time, such as
for 5 minutes, 15 minutes, 30 minutes, one hour, 4 hours,
or up to 24 hours.
Adhesive
In one embodiment,- the stratum-corneum penetrating
device contains an adhesive (e.g., on or outside the skin-
contacting surface of the microprotrusion member to affix
the device to the skin). The adhesive may be coated over
the entire skin-contacting surface of the device, or
preferably, only over the periphery or selected areas-of
the skin-contacting surface. Examples of hydrophobic
adhesives include, but are not limited to, silicones,
polyisobutylenes and derivatives thereof, acrylics, natural
rubbers, and combinations thereof. Examples of 'silicone
adhesives indlude, but are not limited to, Dow Corning 355
available from Dow Corning of Midland, MI; Dow Corning X7-
2920; Dow Corning X7-2960; and GE 6574 available from
General Electric Company of Waterford, NY. Examples of
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acrylic adhesives include, but,are not limited to, vinyl (D
acetate-acrylate) multipolymers such as,Gelva 7371,
available from Monsanto Company of St. Louis, MO; Gelvao
7881; Gelva 2943; and 1-780 medical grade adhesive
available from Avery Dennison of Painesville, OH. Examples
of hydrophilic adhesives include, but are not limited to,
gum papaya and other, natural gums, MC, HEMA, HPMC, EHEC,
HEC, HPC, CMC, PVA (polyvinyl alcohol), PVP (polyvinyl
pyrrolidone), PEO (polyethylene oxide), HEMA, HEEMA,
HDEEMA, MEMA, MEEMA, MDEEMA, EGDMA, NVP MA, VAC,
polycrylamide, gelatins, gum arabic, gum karaya, gum
tragacanth,~guar g1zm, gum benzoin, and alginic acid and
their salts, polyethylene glycol (PEG), and polypropylene
glycol (PPG).
In one embodiment, the concentration of the adhesive
in the adhesive coating layer may range from about 0.1% to
about 95%, by weight, such as from about 1% to about 20%,
by weight, of the carrier.
Devices
In one embodiment, the microprotrusion member is
digitally pushed into.the skin by the user (e.g., the
fingers of the user exert enough pressure for the
microprotrusion member to pierce the stratum corneum).
Finger Cot/Glove
In one embodiment, the stratum-corneum piercing device
of the present invention may be constructed as a part of a
finger cot or a glove with the microprotrusions facing
outwards. By wearing such a finger cot-like or glove-like
device, the user can treat the skin with precision and
ease, especially at certain anatomic sites that require
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precision in application (e.g., around the eye) or are
difficult to reach (e.g., the back). The microprotrusion
member may be located on certain areas of the finger cot-
like or glove-like device that would touch the skin (e.g.,
on the tip area), or may cover the entire surface of the
finger cot-like or glove-like device. The device may also
be used to administer the composition.
Roller
In one embodiment, the stratum-corneum piercing device
may be constructed in the shape of a roller with the
microprotrusions facing outwards. The roller-like
microprotrusion member may be rolled over the skin to be
treated, thus piercing the stratum corneum and delivering
the active agents into the skin. The skin treatment
composition may be applied to the skin prior to, during, or
after the treatment with the roller-like stratum-corneum
piercing device,'which may or may not have one or more
reservoirs containing the composition and/or collection of
bodily fluids. Alternative, the stratum-corneum piercing
device may be constructed with a curved surface to resemble
a portion of a roller (e.g., with a half-cylinder or
quarter-cylinder shape) with the microprotrusi.ons facing
outwards on the curved surface. During an application, one
end of the partial cylinder shaped microprutrusion member
is pressed onto the skin first, followed by a pressing and
"rolling" motion over the skin area to be treated until
reaching the Qther end of microprotrusion member, thus
piercing the skin that has been rolled over with the
device. The main advantage of such a partial cylinder
shaped device over the roller-like stratum-corneum piercing
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device is better control of the applied pressure and
movement.
Impact Implement
In anoth'er embodiment, the user may engage an
implement to push the microprotrusion member into the skin.
In one embod=ent, the stratum-corneum piercing devic-e
includes an implement handle device that may include
springs, pistons, pump(s), sensor(s), and/or
microprocess'or(s) to control the interaction of the
microprotrusion member with the skin. The implement handle
device may include a reservoir, vacuum or positive pressure
source (to collect or expel contents to or from the
reservoir), springs or other potential energy storage
elements, and/or a collar for securing'the microprotrusion
member.
Turning to Figures 3-7, various embodiments of
implement handle devices are shown. Figures 3 and 4 show
one embodiment of a device 100 having a piston assembly 120
including microprotrusion member contacting portion 130, a
main housing portion 160, and an end housing portion 180.
Figure 5 shows an alternate embodiment of implement handle
device 200. In these embodiments, the implement handle
device incorporates two stages to accomplish application of
the microprotrusion member. The first stage has dual
actions, particularly via its normal force to the skin
surface, both to tension the skin and to initiate seating
the microprotrusions into the tensioned skin. The second
stage provides an impact force, which will seat the
r
microprotrusion member to the proper depth into the skin.
The microprotrusion member contacting portion 130 of the
implement handle device 100 provides a uniform distributi-on
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of the force so that the microprotrusion member penetrates
uniformly, that is, the blades penetrate to substantially
the same depth across the contacted skin area.
Figure 4 shows a cross-sectional view of 'Figure 3
taken along lines 4-4. The front portion 164 of the piston
assembly 120 extends into microprotrusion member contacting
portion 130. The rear portion 166 of the piston assembly
contacts impact plunger-170. In the embodiment shown in
Figure 4, internal housing is denoted as 158 and the main
housing is denoted as 160. It, however, is not necessary
that the two housing be separate; in another embodiment the
two may be combined to be a single, integral housing
component.
I To use the handle implement with the microprotrusion
member, the microprotrusion member is first placed on the
skin to be treated. The microprotrusion member contacting
portion 130 of the device is placed over the
microprotrusion,member and pressure is exerted by the user
to set the microprotrusions into the upper stratum corneum.
The pressure on the plunger results in translation of the
piston assembly 120 and impact plunger 170 generating
tension as it pushes against tensioning spring 140.
Tensioning spring 140 may be a straight spring or a conical
spring. The position of impact plunger 170 is eccentric or
skewed, such that as pressure is applied to the piston
assembly, distal end 172 of impact plunger 170 engages edge
178 of impact hammer 176. Once impact hammer 176 is
engaged, piston assembly=120, impact plunger 170, and
impact hamme~ 176 continue to translate together until
impact plunger 170 becomes aligned through plunger guide
168 as the impact plunger "pops" into the impact hammer
hole 174. As this occurs, the plunger and hammer become
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aligned and impact hammer 176 is forced via impact tension
adjustment spring 150 in the-opposite direction over the
end of impact plunger 170 substantially the length of the
impact hammer hole 174 and thereby'creating an impact
force. The impact force results in an audible noise
similar to a click and also an impact perception from
microprotrus=ion member contacting portion 130. When the
implement handle device 100 is'removed from skin, it will
automatically reset itself and be ready for the next
operation.
In this embodiment, there are two springs contained
within housing of -the implement handle device, allowing the
skin to be tensioned each and every time the implement is
used. In one embodiment, the microprotrusion member is
placed on the skin to be treated and set'into the skin by
using implement 100. Alternately, the microprotrusion
member may be affixed to the surface 132 of the
microprotrusion member contacting portion 130 of implement
100. The user would then bring the microprotrusion member
in contact with the skin surface and push the implement
toward the skin surface, thereby setting the
microprotrusion member into the skin.
The microprotrusion member contacting portion 130 of
Figure 3 has surface 132 that may be substantially convex
(shown Figure 4), concave, or flat. In the implement
device handle 200 shown in Figure 5, surface 232 of the
skin-contacting portion 230 is substantially flat.
The amount of force needed to set the microprotrusions
into the skin can vary by skin site or the structure of the
microprotrusions. For example, the skin of the elbow is
thicker than the skin under the eye and may require a
greater force to penetrate into the stratum corneum. In one
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embodiment, the implement provides at least about one pound
of force to force the microprotrusion member into the
stratum corneum, such as from about 1 to about 1-0 pounds of -force.
Rotational Device
.In another embodiment shown in Figures 6 and 7, the
microprotrusion member 320 is incorporated as a part of the
implement handle device 400 to form a stratum-corneuni
piercing device 300. Microprotrusion member 320 is shown
in greater detail in Figures 9 to 10. The microprutrusion
member can also be set at an angle to the longitudinal axis
(not shown).
. Looking at Figure 6, stratum-corneum piercing device
300 is formed by microprotrusion member 320 and implement
handle device 400, which has a rotating/sliding barrel 420.
The microprotrusion member 320 is detachably secured into
the first end 4212 of rotating/sliding barrel 420.
Microprotrusion member 320 may be adapted to be removed and
replaced by the user whenever desired. A cover, such as a
removable cap (not shown) may also be used to cover
microprotrusion member 320.
Figure 7 shows the cross-sectional view of
microprotrusion member 300 along line 7-7. Ring 332 of
microprotrusion member 320 is in juxtaposition to first end
422 of rotating/sliding barrel 420 and forms an insertion
stop. Housing 440 forms the major portion of implement
handle device,400. Rotating/sliding barrel 420 is
positioned su,bstantially within housing 440 at first end
442. The outer diameter of rotating/sliding barrel 420 is
such that barrel 420 is able to slide back and forth
without excessive drag but is such that the fit is fairly
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tight and barrel 42+0 does not shift in its movement or
direction about longitudinal axis X-X (e.g.,- barrel 420
remains substantially coincidental to housing 440).
Housing 440 has first end 442 and 8econd end 444. In the
embodiment shown in Figure 6 and 7, second end 444 is a
rounded end but may be any configuration including flat,
convex, or open. On the interior surface 446 of housing
440, there may be stops or notches to hold springs, gears,
and plungers. In the embodiment shown in Figures 6 and 7,
stop 450 is'located on the interior surface 446 toward
second end 444. The first end 462 of stationary end gear
460 engages'stop 450. End gears 460 can also be made
integral to housing 440. Second end 464 of stationary end
gear 460 engages end cap 470. The interface between the
stationary end gear 460 and end cap 470 zinay include
intermeshing teeth, which provides ratcheting during
rotation of end cap 470. Within end cap 470, rotating and
sliding gear 480 is inserted. Gear 480 has compression
spring 484 about shaft 482. Shaft 482 is aligned with and
fits into collar 472, which is integral to end cap 470.
This arrangement forms a stop for first end 486 of
compression spring 484. Second end 488 of compression
spring 484 fits into rotating sliding gear 480 which then
fits into front stationary gear 490 to form stop 492.
Shaft 482 extends through front stationary gear 490 to
contact plunger 500. In the embodiment shown in Figure 7,
shaft 482 is threaded, with stationary gear 490 movable
about the threads in shaft 482 and mating threads in gear
490. This allows plunger 500 to move toward
rotating/sliding barrel first end 422 as the
microprotrusion member is applied to the skin.
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As previously mentioned, rotating/sliding barrel 420
fits within first end 442 of housing 440. Rotating/sliding
barrel 420 has at least one, preferably two or more,
rotational grooves shown as 424. Barrel 420 is also
preferably substantially clear such that the amount of
composition within the barrel can be visualized by the
user. Engaging rotational groove 424 is key 448 on the
inner surface of housing 440. In the embodiment shown in
Figure 7, there are two keys 448. In the embodiment shown
in Figure 7, groove 424 threads in a helical direction.
When groove 424 engages key 448, the movement of the
rotating/sliding barrel is also in a helical manner, that
is, the rotating/sliding barrel extends away from second
end 444 while sligYitly turning. Within rotating/sliding
barrel 420 is reservoir 430. Plunger 500 may engage any
composition contained within reservoir 430, thereby
expelling the contents through microprotrusion member 320.
In the embodiment shown in Figures 6 and 7, the plunger
incrementally advances toward first end 422 with each
successive application. In one embodiment, the motion
results in the microprotrusion member 320 being rotated.
In another embodiment, the motion results in the
microprotrusion member(s) being translated or translated
and rotated. In one embodiment, an audible sound is also
produced. In another embodiment, a light indicator or
other indicater is utilized. In another embodiment, the
helical action described in this.invention may be precisely
and automatically, controlled by a electrical mot-or (not
shown). A cixcuitry and/or power source for such motor can
also be housed inside, e.g. inside implement device 400.
In one embodiment, the user first contacts
microprotrusion member 320 with the skin by holding
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microprotrusion member 320 in a generally perpendicular
manner to the skin surface. The user then gently pushes
the microprotrusion member into the skin. By applying a
force greater than that required by compression spring 486
to compress, 'the microprotrusion member penetrates the
stratum corneum. As the pressure is exerted by the user,
the microprotrusion member and barrel 420 translates and
rotates through and about the longitudinal axis X-X of the
implement handle device 400, moving the microprotrusion
member in a'circular manner relative to the surface of the
skin; that is, the microprotrusion member rotates while
contacting And/or,entering the skin.
This type of penetration provides a larger pierced
area than an area that has just had the microprotrusion
member applied to in a non-rotated manne'r. Use of an
implement such as-described to set a microprotrusion member
into the skin may provide repeatable function and
penetration of the microprotrusions into the stratum
corneum. The,microprotrusion member then resets with an
audible click for the next use. The thread pitch and
cross-sectional area of the plunger control the amount of
composition applied to the skin.
The microprotrusion member of the device is adapted to
rotate about 70 degrees lateral to the surface of the skin.
In one embodiment, the amount of rotation of the .device may
be designed to be at least about 5 degrees, such as from
about 20 to about 360 degrees, such as from about 45 -to
about 135 degrees.
An advantage to the embodiment shown in Figur.es 6 and
7 is that a composition that is delivered from reservoir
430 is positively displaced by the plunger at the same time
as the stratum corneum is pierced from the same device.
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In one embodiment, the stationary end gear 460 and the
bottom of the end cap 470 intermeshes and allows for one
way rotation of the end relative to the outer housing.
The microprotrusion member 320, thus, allow controlled
piercing of the stratum corneum, pressure, torque,
rotation, and dispensing of a specific amount of
composition to the skin. For the device shown in Figures 6
and 7, the microprotrusion member 320 is applied to the
skin, the rotating/sliding barrel assembly (including
rotating barrel 420, microprotrusion member 320, front
stationary gear 490, plunger 500, threaded shaft 482, and
rotating/sliding gear 480), translates along the
longitudinal axis of the housing assembly (including
housing 440, end cap 470, and stationary end gear 460).
During this translation, the rotating/sliding barrel
assembly also rotates about the longitudinal axis X-X of
the housing assembly, with the exception of the threaded
shaft 482 and the rotating sliding gear 480. That is to
say the threaded shaft 482 and the'rotating/sliding gear
480 remain rotationally fixed to housing assembly during
this first stage of motion.
The end cap 470 is held fixed during this stage of
motion due to a one-way rotation, mating ratchet
configuration with the first end 462 of stationary gear
460. The end cap 470 restricts the rotation of both the
rotating/ sliding gear and the threaded shaft 482. That is
to say the threaded shaft 482 and the rotating/sliding gear
480 remains rotational fixed to the end cap in.this device.
As a reqult of the described motion above, front
stationary gear 490 rotates relative to both the mating
threaded shaft 482 and the sliding/rotating gear 480. This
relative rotation between the threaded shaft 482 and the
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front stationary gear 490, results in translation of the
shaft 482 and plunger 500 relative to the.rotating sliding
barrel 420, pushing out a measured dose of product from the
reservoir 430.
The relative rotation between the sliding/rotating
gear 480 and the front stationary gear 490 is restricted to
one-way rota,~ion, due to a mating ratchet configuration
between the sliding/rotating gear 480 and the front
stationary gear 490. As the end of the translation and
rotation stroke is approached, the front stationary gear
490 ratchets pop over the corresponding sliding/rotating
gear ratchet, crea,ting a signal to notify the user that the
limit of rotation, translation, and pressure for this
application has been reached.
During the described motion above, the spring 484 is
compressed, providing a measurable and controllable force
measured at the surface contact area. This compressed
spring force also maintains engagement of the mating
component mating areas for constant engagement of ratchets
mating surfaces during translation and rotation.
The relative helical motion between the
rotating/sliding barrel assembly and the housing assembly
is created through incorporation of a helical groove(s) 424
located in the barrel 420 and the mating key(s) 448 in the
housing 440. This motion, however, could also be created
through many methods know in the art such as rack and
pinion, ball screw, mating screws, etc. Another embodiment
includes the key being located on the barrel and the
grooves being located in the housing.
The second motion and method of action describe here
in occurs with the removal of the device from the contact
surface area. At this point in time the rotating/sliding
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barrel assembly has substantially reached its designed
motion limit within the housing, and the spring 484 is
substantially compressed.
As the user begins to remove the device from the area
of contact, the user motion is opposite to the contact
area. As this occurs, the rotating/sliding barrel assembly
translates along the longitudinal axis X-X of the housing
assembly, remaining in contact with the contact surface.
During this translation, the rotating/sliding barrel
assembly also rotates about the longitudinal axis X-X of
the housing assembly opposite the application rotation,
this time including the threaded shaft 482 and the rotating
sliding gear 480. That is to say that the threaded shaft
482 remains substaritially fixed in position to the mating
threads of the front stationary gear 490, allowing only
one-way translation of the shaft and piston relative to the
barrel reservoir 430, minimizing potential contamination of
the device from,external contaminants. This rotation also
provides a controlled spreading of 'dispensed product over
and/or into the contacted area.
The end cap 470 rotates substantially with the
rotating/sliding barrel assembly, during this motion. The
mating ratchet configuration with the stationary gear 460
allows one-way rotation in this direction. When the
translation limit is reached, the ratchet(s) of the end cap
470 jumps over the corresponding ratchet(s) of the end
stationary gear 460, providing a click to notify the user
that the device is reset,and ready for the next
application. The compression spring 484 is either fully
extended or at it minimal compressed state at this point.
The implement may be made from a variety of suita-ble
materials. In one embodiment, the plunger 500 is made from
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a softer material than the shaft 482. For example,.in one
embodiment, plunger 500 is made from a low-density
polyethylene while the shaft is made from an acetal
copolymer.
Figures''9-10 show in detail one embodiment of
microprotrusion member 320 (Figure 10 is a cross-section
view of micr,Qprotrusion member 320 along line 10-10).
Microprotrusion member 320 has-outer housing 330, which
includes ring 332. As seen in more detail in Figure 11,
inner housing 340 fits within outer housing 330 and secures
microprotrusion member 500. Microprotrusion member 500
contains microprotrusions 520 and skin-contacting surface
540.
The device can also be designed to create a negative
pressure/vacuum for removal of fluid upon contact to the
surface or externally triggered by the user. In one
embodiment, this can be done in either a single or two step
process. In an example of a single step process, the
device is applied to the skin as previously described. The
motion causes the plunger 500 to recede into the reservoir
away from the tip creating a vacuum or negative pressure at
the tip. The amount of vacuum created is a function of
the amount of air displaced. The reservoir in this case
is a vacuum reservoir, not to be used for composition
delivery.
In an example of a two-step process, the user would be
required to reset the device prior to engaging the contact
surface. An example of this would allow the user to push
in or pull back a lever to store the required potential
through a spring or other potential energy storage device.
Then the device would be applied to the contact area, the
potential energy would be released creating the motion
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necessary to produce the vacuum. This embodiment would
allow isolation of the force required for application of
the'micro protrus'ion to create the punctures and the force
required to create the vacuum.
In both the single and two-step process listed above,
the mechanical energy /action provided by the user could be
replaced by using stored electrical energy to drive a motor
(linear or rotary) to create the desired motion of the
piston and,.therefore, the vacuum. A vacuum pump could
also be used.
The device could further be designed to incorporate
both a composition reservoir(s) and a vacuum reservoir for
both removal of liquid and application of composition from
the same device. Cdncentric or "side by side" reservoirs
could be utilized with separate plungers to both create the
vacuum and dispense the composition within the same device.
Compressible Cover Device
In another embodiment, the implement is a stick-like
structure that does not have any gears or rotational
ability. The microprotrusion member may be again placed on
the skin with the implement used to set the
microprotrusions into the skin. Alternately, the
microprotrusion member may be attached to an end of the
implement. The user would then grip the impl.ement and push
the microprotrusion member into the skin. The implement may
have any shape. In one embodiment, the outer surface of the
implement can be seen in,Figure 6 but have no movable
internal parts.
In one embodiment, the stratum corneum-piercing device
includes a handle having a first end, at laeast one stratum
corneum-piercing microprotrusion attached at the first end,
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and a compressible"cover where the compressible cover
substantially encases the at least one stratum corneum-
piercing microprotrusion. Examples of this type of device
are shown in Figures 12-13.
The handle may be a rod-shaped structure that the user
holds during use. The handle may be solid or hollow. In one
embodiment,,the handle is hollow and forms a reservoir that
can store a composition and that is in communication with
the first end such that the composition may.be release from
the reservoix at the first end and applied to the treatment
site.
The handle may also contain a vacuum. Such an
embodiment would assist in the expulsion of fluids from a
pimple. In one embodiment, the vacuum in the range of from
about 0.1 to about 0.99 atm, such as from about 0.2 to
about 0.8 atm.
In one embodiment, as shown in Figure 12, device 810
has a first end 830, a second end 840, two microprotrusions
804, compress~ble cover 812, and a handle 850. In one
embodiment, as shown in. Figure 13, second end 84,0 also has
a second compressible cover 860.
Handle 850 may be solid or a hollow tube-like
structure. Handle 850 may contain one or more compositions
for delivery to the treatment site and/or a vacuum
collecting body fluids, such as pus or wound exudates, from
the treatment site. In one embodiment, handle 850 is a tube
that contains a composition and is in communication with
the first end 830, the second end 840, or both. Handle 850
may be attached to microprotrusion member 802 by an
adhesive, suchas cyanoacrylate glue, or other means.
In one embodiment, the walls of the handle 850 are
flexible, making it is possible that any composition
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contained therein may be expelled upon squeezing the handle
850 (e.g., either through the first end or the second end).
In one embodiment~, a composition 822 is contained within
the handle 850 does not penetrate the compressible cover
812 until a seal 818 at the first end 830 is broken by
bending the handle 850. For example, Figure 13 shows a
hollow handle 850 in which a composition 822 in the form of.
a fluid is contained. By exerting pressure and breaking
seal 818, composition 822 can freely flow and saturate the
compressible cover 812.
In one embodiment, the handle 850 contains an second
compressible cover 860 that is absorbent. The second,
compressible cover 860 may be made of absorbent material.
In one embodiment, as shown in Figure 13,
microprotrusion device 802 is not integral to handle 50 but
rather a separate tip unit 814 that may be attached or
removed by a threading mechanism 816.
In another,embodiment shown Figure 14, stratum-corneum
piercing device 1000 is formed by rriicroprotrusion member
1020 and implement handle 1100. Microprotrusion member
1020 is shown in greater detail in Figures 15 and 16.
Microprotrusion member 1020 has compressible cover
1012, reservoir 1070 and may have a plurality of
microprotrusions. In the embodiment shown in Figures 15
and 16, there are at least two types of microprotrusions,
delivering microprotrusions 1040 and withdrawing
microprotrusions 1060. The delivering microprotrusions
1040 have an open end 1052, a closed end 1062 and have at
least one port 1050, which prior to application is located
within reservoir 1070. Withdrawing microprotrusion 1060 has
a first open end 1073 and a second open end 1074, the
second open end 1074 extending into the implement handle
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1100. in one embodiment, there are at least two delivering
microprotrusions and one withdrawing microprotrusion.
The compressible cover 1012 may contain an active
agent or a composition. Additionally, reservoir 1070 may
contain such active agent or composition.
Implement handle 1100 has collection chamber 1200,
which may be.,.an empty chamber at standard pressure, reduced
pressure, or increased pressure. Withdrawing
microprotrusion 1060 extends into collection chamber 1200
such that when in use, fluid may be (i) withdrawn from the
tissue into the collection chamber 1200 or (ii) delivered
from the collection chamber 1200 to the tissue.
In use, the user places the microprotrusion member
1020 against the surface of the tissue (such as skin having
a pimple or affected by acne). By applying pressure to the
device, the compressible cover 1012 and reservoir 1070 are
compressed, and the microprotrusions begin to penetrate
through the compressible cover 1012 and into the tissue.
As the compressible cover 1012 and reservoir 1070 are
compressed (shown Figure 16), they provide support for
microprotrusion and may prevent smaller diameter
microprotrusions from buckling under the pressure exerted
during use. The compressed compressible cover 1012 and
compressed reservoir 1070 may form a stop such that the
length of the microprotrusions extending into the tissue
may be controlled.
If the reservoir 1070 contains a composition,
compression of the reservoir will also force the
composition up through the delivering microprotrusions 1040
such that the composition is delivered into the tissue. Iri
particular, the composition may contain an anti-acne agent
that is delivered into a pimple. if the collection chamber
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1200 is under reduced pressure, the withdrawing
microprotrusion 1060 may withdraw fluid from the target
area (e.g., if the tissue is a pimple, the device 1000 may
removed pus that is stored in the collection chamber 1200).
In one embodiment, the delivering microprotrusions
1040 push a solution into the pimple and by positive
displacement, fluid from the pimple is then forced through
the withdrawing microprotrusion 1060 and into the
collection chamber 1200.
Once the treatment is complete, the user can remove
the microprotrusion member 1020 from the tissue. The
compressible cover 1012 and reservoir 1070 may return-the
non-compressed state as shown in Figure 14 (e.g., open ends
1052 of the delivering microprotrusions 1040 and first open
end 1072 of withdrawing microprotrusion 1060 would then be
stored within the compressible cover 1012, providing
protection against accidental application).
Adhesive devices
In one embodiment, after application of the device, an
adhesive film or sheet is applied to a treated pimple site
to further remove the semisolid or solid biological
materials from the pimple. Such adhesive film or sheet can
be made from, but not limited to, adhesive resins such as
cyanoacrylate based resins, pressure-sensitive adhesive
such as those'containing a cationic polymer and plasticizer
as described in PCT Patent Application No. W000/33796 Al),
a keratotic plug remover.composition as described in US
Patent No. 5,,512,277, and polymer film forming adhesive
material using cationic, or anionic or polar polymers or
copolymers such as Gantrex copolymers sold by
Internationals Specialty Products (Wayne, NJ).
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Composition
The composition may-be solid, semisolid, liquid or any
combination thereof. In particular, the solid compositions
include but are not limited to bart, sticks, powders (such
as micro-particles and nanoparticles), masks, and patches.
Examples of semisolid compositions iriclude but are not
limited to creams, lotions, gels, ointments, hydrogels,
hydrocolloids, foams, mousses,'emulsions, micro-emulsions,
and nano-emulsions. Examples of liquid compositions
include but'are not limited to cleansers, t.oners, serums,
liquid sprays, and aerosols. Included are those
composition6 used~to treat the aforementioned skin
disorders. The composition may contain an active agent
(e.g., contains a cosmetically-acceptable, safe and
effective amount of such active agent): '
In one embodiment, a composition is applied to the
skin prior to piercing of the stratum corneum by the
microprotrusion member. The composition is then "pushed"
into the openings in the skin as the microprotrusion member
pierces the skin. In another embodiment, the skin treating
composition is present on the microprotrusion member. The
composition may be coated on the microprotrusions and/or
the skin-contacting surface. One example of a coating is
described in European Patent No. 914,178. In this
embodiment, the composition may be pushed into the skin as
the openings are formed or may "fi11 in" the openings after
they are formed. It has been found that the openings close
up within a relatively short time period after forming.
Thus, in one embodiment, the coatings are optimized such
that as the impact force of the microprotrusion member both
pierces the stratum corneum and delivers the composition or
active agent to the skin. In one embodiment, the
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composition is applied to at least a portion of the surface
microprotrusion member proximate to the time of application
to the skin.
In still another embodiment, the skin treating
composition is contained in the reservoir of the
microprotrusion member or handle implement. In this
embodiment, the composition may be pushed into the skin
during penetration or placed on the skin after penetration.
In one embodiment, the composition contains one or
more active agents. What is meant by an "active agent" is a
compound (e.g., a synthetic compound or a compound isolated
from a natural source) that has a cosmetic or therapeutic
effect on the body (e. g., a material capable of exerting a
biological effect on the skin) such as therapeutic drugs,
including, but not limited to, organic and
macroionmolecular compounds. Examples of such therapeutic
drugs include peptides, polypeptides, proteins, and nucleic
acid materials containing DNA; and nutrients. Examples of
polypeptide and protein active agerits include growth
hormone releasing factor (GRF), nerve growth factor,
melanocyte inhibitor-I, vaccines, botox (Botulinum
neurotoxins), cyclosporin and its derivatives (e.g.,
biologically active fragments or analogs). Other active
agents include anesthetics; analgesics (e.g., lidocaine,
lidocaine plus epinephrine, prilocaine, tetracaine,
fentanyl, and,salts thereof such fentanyl citrate); anti-
inflammatory agents; antibiotics, antifungals, antiviral
and other antimicrobial agents; antioxidants;
immunosuppressive agents and immunostimulants.
In one embodiment, the composition contains an anti-
acne agent. What is meant by an anti-acne agent is an.
compound that has been approved by the U.S. Food and Drug
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Administration for the topical treatment of acne and/or
rosacea. Examples of.anti-acne agents include, but are not
limited to, salicylic acid, azaleic acid, benzoyl peroxide,
sulphur, retinoic acid, tazarotene; candida
bombicola/glucose/methyl rapeseedate ferment, peat water,
resorcinol, silt, peat, permethin, clindamycin, adapalene,
erythromycin-, sodium sulfacetamide, and combinations
thereof. In one embodiment, th.e amount of anti-acne agent
in the composition is from about 0.01% to about 10%, for
example froni about 0.1% to about 5%, or from about 0.5% to
about 2% by weight, based on the total weight of the
composition:
In one embodiment, the device of the present invention
contains an anti-aging agent. Examples of suitable anti-
aging agents include, but are not limited to: inorganic and
organic sunscreens such as titanium dioxide, zinc oxide,
and octyl-methoxy cinnamates; retinoids; botox (Botulinum
neurotoxins); dimethylaminoathanol (DMAE); copper
containing peptides; vitamins such as vitamin E, vitamin A,
vitamin C, and vitamin B and vitamin salts or derivatives
such as ascorbic acid=di-glucoside and vitamin E acetate or
palmitate; alpha hydroxy acids and their precursors such as
glycolic acid, citric acid, lactic acid, malic acid,
mandelic acid, ascorbic acid, alpha-hydroxybutyric acid,
alpha-hydroxyisobutyric acid, alpha- hydroxyisocaproic
acid, atrrolactic acid, alpha- hydroxyisovaleric acid,
ethyl pyruvate, galacturonic acid, glucoheptonic acid,
glucoheptono 1,4- lactone, gluconic acid, gluconolactone,
glucuronic acid, glucuronolactone, isopropyl pyruvate,
methylpyruvate, mucic acid, pyruvic acid, saccharic acid,
saccaric acid 1,4-lactone, tartaric acid, and tartronic
acid; beta hydroxy acids such as beta- hydroxybutyric acid,
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beta-phenyl-lactic acid, and beta-phenylpyruvic acid; zinc
and zinc containing compounds such as zinc oxides; and
botanical extracts such as green tea, soy, milk thistle,
algae, aloe, angelica, bitter orange, coffee, goldthread,
grapefruit, hoellen, honeysuckle, Job's tears,
lithospermum, mulberry, peony, puerarua, nice, and
safflower; and salts and prodrugs thereof.
In one embodiment, the composition contains a
depigmentation agent. Examples of suitable depigmentation
agents include, but are not limited to: hydroquinone;
lignin peroxidase; mushroom enzymes; hydrogen peroxide;
diodic acid; discetyl bolidine; undecylenoyl phenylalanine;
glutathione reductase; soy extract; soy isoflavones;
retinoids such as retinol; kojic acid; kojic dipalmitate;
hydroquinone; arbutin; transexamic acid; vitamins such as
niacin and vitamin C; azelaic acid; linolenic acid and
linoleic acid; placertia; licorice; and extracts such as
chamomile and gteen tea; and salts and prodrugs thereof.
In one embodiment, the composition contains a plant
extract. Examples of plant extracts include, but are not
limited to, feverfew, soy, glycine soja, oatmeal, what,
aloe vera, cranberry, hazel witch, alnus, arnica, artemisia
capillaris, asiasarum root, birch, calendula, chamomile,
cnidium, comfrey, fennel, galla rhois, hawthorn,
houttuynia, hypericum, jujube, kiwi, licorice, magnolia,
olive, pepperinint, philodendron, salvia, sasa albo-
marginata, natural isoflavonoids, soy isoflavones, and
natural essential oils. -
In one embodiment, the composition contains metals
such as metal ions, metal salts, metal complexes, fine
metal powders, fine metal coated fibers and fabrics of
synthetic or natural origin, or fine metal fibers. Examples
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of such metals include, but are not limited to, zinc,
copper, aluminum, gold, silver, titanium.., The metal ions
provide benefits such as antimicrobial, anti-inflammatory,
and/or sebum-reduction effects.
In one einbodiment, the composition contains
nanoparticles such as nanoparticles containing silver.
Other aQtive agents include.those commonly used as for
topical treatment and in cosmetic treatment of skin
tissues, such as topical antibiotics for wounds, topical
antifungal drugs to treat fungal infections of the skin,
and antipsoriatic drugs to treat psoriatic lesions of the
skin. I
Examples of antifungal drugs include but are not
limited to miconazole, econazole, ketoconazole,
sertaconazole, itraconazole, fluconazole; voriconazole,
clioquinol, bifoconazole, terconazole, butoconazole,
tioconazole, oxiconazole, sulconazole, saperconazole,
clotrimazole, undecylenic acid, haloprogin, butenafine,
tolnaftate, nystatin, ciclopirox olamine, terbinafine,
amorolfine, naftifine, elubiol, griseofulvin, and salts and
prodrugs thereof. In one embodiment, th.e antifungal drugs
are an azole, an allylamine, or a mixture thereof.
Examples of antibiotics (or antiseptics) include but
are not limited to mupirocin, neomycin sulfate bacitracin,
polymyxin B, 1- ofloxacin, tetracyclines (chlortetracycline
hydrochloride, oxytetracycline-10 hydrochloride and
tetrachcycline hydrochoride), clindamycin phsphate,
gentamicin sulfate, metronidazole, hexylresorcinol,
methylbenzethonium chloride, phenol, quaternary ammonium
compounds, tea tree oil, and their cosmetically acceptable
salts and prodrugs.
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Examples of antimicrobials.include but are not limited
to salts of chlorhexidine, such as iodopropynyl
butylcarbamate, diazolidinyl urea, chlorhexidene
digluconate, chlorhexidene acetate, chlorhexidene
isethionate, and chlorhexidene hydrochloride. Other
cationic antimicrobials may also be used, such as
benzalkonium chloride, benzethonium chloride, triclocarbon,
polyhexamethylene biguanide, cetylpyridium chloride, methyl
and benzothonium chloride. Other antimicrobials include,
but are not limited to: halogenated phenolic compounds,
such as 2,4,4',-trichloro-2-hydroxy diphenyl ether
(Triclosan); parachlorometa xylenol (PCMX); and short,chain
alcohols, such as ethanol and propanol. In one embodiment,
the alcohol is preferably at a low concentration (e.g.,
less than about 10% by weight of the composition, such as
less than 5% by weight of the composition) so that it does
not cause undue drying of the skin.
Examples of antipsoriatic drugs or drugs for
seborrheic dermatitis treatment indlude, but are not
limited to, corticosteroids (e. g., betamethasone
dipropionate, betamethasone valerate, clobetasol
propionate, diflorasone diacetate, halobetasol propionate,
triamcinonide, dexamethasone, fluocinonide, fluocinolone
acetonide, halcinonide, triamcinol-one acetate,
hydrocortisone, hydrocortisone venerate, hydrocortisone
butyrate, aclometasone dipropionte, flurandrenolide,
mometasone furoate, methylprednisolone acetate),
methotrexate, cyclosporine, calcipotriene, anthraline,
shale oil and derivatives thereof, elubiol, ketoconazole,
coal tar, salicylic acid, zinc pyrithione, selenium
sulfide, hydrocortisone, sulfur, menthol, and pramoxine
hydrochloride, and salts and prodrugs thereof.
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Examples of arriti-viral agents for viral infections
such as herpes, include, but are not limited to, imiquimod
and its derivatives, podofilox, podophyllin, interferon
alpha, acyclovir, famcyclovir, valcyclovir, reticulos and
cidofovir, arid salts and prodrugs thereof.
Examples of anti-inflammatory agent, include, but are
not limited to, suitable steroidal anti-inflammatory agents
such as corticosteroids such as hydrocortisone,
hydroxyltriamcinolone alphamethyl dexamethasone,
dexamethasone-phosphate, beclomethasone dipropionate,
clobetasol valerate, desonide, desoxymethasone,
desoxycorticostero,ne acetate, dexamethasone, dichlorisone,
diflorasone diacetate, diflucortolone valerate,
fluadrenolone, fluclarolone acetonide, fludrocortisone,
flumethasone pivalate, fluosinolone acetonide,
fluocinonide, flucortine butylester, fluocortolone,
fluprednidene (fluprednylidene)acetate, flurandrenolone,
halcinonide, hydrocortisone acetate, hydrocortisone
butyrate, metlaylprednisolone, triamcinolone acetonide,
cortisone, cortodoxone, flucetonide, fludrocortisone,
difluorosone diacetate, fluradrenalone acetonide,
medrysone, amciafel, amcinafide, betamethasone,
chlorprednisone, chlorprednisone acetate, clocortelone,
clescinolone, dichlorisone, difluprednate, flucloronide,
flunisolide, fluoromethalone, fluperolone, fluprednisolone,
hydrocortisone valerate, hydrocortisone
cyclopentylproprionate, hydrocortamate, meprednisone,
paramethasone, prednisolone, prednisone, beclomethasone
dipropionate, betamethasone dipropionate, triamcinolone,
and salts are prodrugs thereof. A second class of anti-
inflammatory agents which is useful in the compositions of
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the present invention includes the nonsteroidal anti-
inflammatory agents.
Other active agents include, but are not limited to,
wound healing enhancing agents, such as recombinant human
platelet-derived growth factor (PDGF) arrd other growth
factors, ketanserin, iloprost, prostaglandin E1, collagens,
hyaluronic acids, scar reducing agents such as mannose-6-
phosphate, matric metalloprotease (MMP) inhibitors (as in
US Patent No. 2006/0074108 Al), P-38 inhibitors, analgesic
agents, anesthetics such as benzocaine, lidocaine,
tetracaine, acetaminophen; hair growth enhancing agents
such as minoxadil, hair growth retarding agents such as
eflornithine hydrochloride, anticancer agents', endocrine
and metabolic medication, neurologic medications,
vasoconstrictors, vasodilators, and biologics such as
proteins, peptide, and enzymes.
Use of Composition with Device
In one embodiment, the activeagent or composition is
coated on (i) at least a portion,of the skin-contacting
surface, (ii) at least a portion of one or more of the
stratum-corneum piercing microprotrusions, or (iii) at
least a portion of the skin-contacting surface and at least
a portion of one or more of the stratum-corneum piercing
microprotrusions prior to application to the skin. In this
embodiment, when device is applied onto the skin, it
transfers at least a portion of the active agent or
composition onto the same area of the skin that is being
pierced. In one embodiment, the microprotrusion member is
affixed to a patch. In one embodiment, the active agent or
composition is contained in the compressible cover.
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In one embodiment, the device includes a reservoir
containing the composition, the skin-contacting surface has
at least one opening, and the reservoir is in communication
with the at least one opening such,that the composition can
move from the'reservoir, through the at least one opening,
and onto the skin.
In one,embodiment, the device includes a reservoir
containing the composition, wherein at least one of the
microprotrusions is hollow and the reservoir is in
communication with the at least one hollow microprotrusion
such that the composition can move from the reservoir and
through the'microprotrusion into the skin. In one
embodiment, the composition moves through the at least one
hollow microprotrusion while the at least one hollow
microprotrusion is in the skin.
In one embodiment, the device is arranged to deliver
from about 0.001 to about 1 ml, such as from about 0.1 to
about 0.2 ml of the composition. The device may deliver
only one dose,of composition or multiple dosages.
In one embodiment, the active agent and/or composition
is applied to the skin proximate to the time of the
piercing the stratum corneum of the skin with the stratum
corneum-piercing device (e.g., within about an hour before
or after the piercing, such as within about fifteen minutes
or within about five minutes).
In one embodiment, the composition includes an anti-
coagulant, such as citric acid and salts thereof, aspirin,
EDTA, dextrin, and sodium sulfate.
Product
In one embodiment, the device of the present invention
and its companion products are packaged together and
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marketed as a kit. The examples of the items in the kit.may
include, but are not limited to, the device including a
microprotrusion member, a predetermined number of
replaceable microprotrusion members (such as the
replaceable microprotrusion tips/attachments), a topical
treatment composition in a suitable container/dispenser
(such as a tube, a bottle, a pump, a jar, a dropper, a or
unit-dose dispenser) to be used before, during, or after
the stratum-corneum piercing device application. The kit
may also include the energy devices (device to generate
therapeutic light, electric, magnetic, electromagnetic,
acoustic, thermal, m.echanical energies). Additionally, the
kit may also contain a cleansing product to be used to
sanitize/sterilize~the skin prior to the device
application. The kit may also include a film forming
composition or bandage to be used after treatment to
protect the treated skin site and to enhance the
therapeutic efficacies for the treated skin.
Methods of Use
The present invention is useful in treating a skin
disorder, in particular, the surface of the skin of the
face (such as the nose), scalp, or lips. The
microprotrusion may be pushed against the surface of the
skin by force such as rubbing, manual direct pressure, or
through the use of an implement. In one embodiment, the
implement contains at least one member (e.g., a spring or
other potential energy storage element) to control the
amount of force. In one embodiment, a device having a
single microprotrusion is used multiple times to provide at
least two different channels in the skin surface. In one
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embodiment, the device is contacted with mucosal membranes
such as mucosal membranes of the oral or vaginal cavities.
In another embodiment, the device is contacted with
the soft tissue of the teeth by piercing the membrane of
the tissue by microprotrusion, the user does not experience
the pain, bleeding and other physical and psychologic
trauma assoc=iated with needle injection. Compositions,
especially those with active agents, such as anesthetics,
anti-inflammatories, anti-bacterials, tissue growth
promoters, or gum healing or gum health agents, can be
delivered into the target site to either (i) prepare the
teeth or gum/tissue for treatment of cleaning, drilling,
extracting and filling and/or (ii) treat the gum/tissue
diseases including but not limited to periodontal, or
gingival nature.
By piercing'the stratum corneum, the skin is
disrupted. By only piercing the stratum corneum and/or
other layers of the epidermis, the user does not feel pain,
trauma (e.g., bleeding and swelling), and/or other
discomfort of the viable dermis being penetrated.
Compositions, especially those with active agents, can be
transported through the disrupted skin. The treatment may
be localized, such that the target site of a pimple or
other blemish, a wrinkle, a razor bumps/ingrown hairs, a
herpes sore, a skin infection, an age-spot, or any other
skin disorder.
As mentioned throughout the detailed des-cri=ption,
there are many means for using the devices diaclosed to
obtain multiple benefits. For example, the microprotrusion
member may be used with or without an implement, a
composition containing an active agent may be placed on the
treatment site prior to, during, or after treatment, the
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microprotrusion member may be coated with a composition.
containing an active agent, and=the benefits derived from
, =
the invention may include treatixig acne, scars, wrinkles,
PIH, or other skin disorders. In one embodiment, the
treatment is substantially painless and does not cause
scarring or bleeding. The treatment may also be used to
withdraw bodily fluid such as pus from a pustule or wound
exudates from the skin.
In one embodiment, the skin disorder is treated by:
(a) affixing a microprotrusion to skin in need of such
treatment (e.g., skin afflicted with such skin disorder);
(b) applying pressure to the microprotrusion member such
that one or more of the microprotrusion penetrates the
stratum corneum; and (c) removing the microprotrusion
member from the diseased skin. in another embodiment, the
method further includes applying a composition to the skin
site proximate in time to application of the
microprotrusion Ynember.
Electric Simulation
In one embodiment, the treatment is followed by a
treatment with electric stimulation. Electric stimulation
is known to enhance tissue repair processes such as
improving wound healing and increasing collagen production.
Electric stimulation is also used in needleless electric
acupuncture p'rocedures to treat diseases by application
directly to body's acupuncture points on the skin. The use
of an electricity-generating patch or mask to provide
electric stimulation to the skin, and particularly, at the
selected acupuncture points beneficial to the dermal and
underlying tissues, for the purpose of treating skin
diseases or disorders (such as acne, dermatitis, wrinkles,
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etc.) has been disclosed in U.S. Patent Application
Publication No. 2004/0267169 Al and U.S. Patent Application
No. 11/019557 filed December 22, 2004.
In one embodiment of the present invention, prior to
application o'f the electricity-generating patch/mask, the
stratum-corneum piercing device is used to disrupt the skin
at the desired location(s) of the skin, such as the
selected acupuncture points, wrinkles, or acne, to reduce
the electric resistance of the skin at these locations,
thereby, indreasing the electric current passage at the
selected skin locations to enhance the desirable effect of
electric stimulation.
In addition, after disrupting the stratum corneum or
epidermis with the stratum-corneum disruptive device, in
order to further enhance electric stimulation efficacy, the
conductive carrier of the electricity-generating device may
contain a relatively high concentration of cosmetically
acceptable organic solvent, (e.g., glycerin, propylene
glycol, or polyethylene glycol), or a non-conductive solute
(e.g., low molecular weigh sugars, dextrans, or urea) to
make the aqueous conductive carrier hypertonic, thus
preventing the stratum corneum layer from hydrating to
become more conductive. Prevention of the stratum corneum
hydration reduces electric current passing through the skin
except at the skin areas where the stratum corneum has been
disrupted by the microprotrusion member treatment.
One example using the microprotrusion treatment for
enhancing electric stimulation efficacy is to use the
stratum-corneum piercing device of the present invention
over a wrinkle or selected acupuncture points of the skin
first, followed by application of an electricity-generating
patch to cover the skin area for electric stimulation
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treatment. Another example is to apply the microprotrusion
spot treatment device to the disease skin areas (e.g.,
acne, acne scar or age spots) or selected acupuncture
points first, followed by application of an electricity-
generating patch to cover the skin area for electric
stimulation treatment. Alternatively, the microprotrusion
member of the present device is built into the electricity-
generating patch/mask devices, powered by a power source,
such as battery, piezoelectric, electric-mechanical (e.g.,
a coil magnet), or by a galvanic couple, as described in
U.S. Patent Application No. 11/019557 filed December 22,
2004, so that processes of stratum corneum disruption-and
electric stimulation are conducted with the same device
without the need o~ changing devices during the treatment.
Iontophoretic Delivery of Active Agents
In one embodiment, there is one or more active agents,
ionic or nonionic in nature, in the conductive carrier of
the electricity-generating patch/mask that will be
delivered into the skin primarily through the pathways of
disrupted stratum corneum by the micropx'otrusion member of
the present invention. One example of the active agent is
Botox (Botulinum neurotoxins). Briefly, a device of the
present invention applied over a wrinkle, followed by
application of an electricity-generating patch to cover the
skin area forlelectric stimulation treatment. The carrier
of the-electricity-generating patch contains Botox as the
active agent that will be delivered into the target skin
and underlyir}g tissues by means of electrotransport (e.g.,
iontophoresis and electroosmosis). Alternatively, the
microprotrusibn member of the present device is built into
the.electricity-generating patch/mask devices with Botox in
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the carrier of the electricity-generating patch such as
that described in U.S. Patent Application No. 11/019557
filed December 22, 2004, so that processes of stratum
corneum disruption and electrotraneport of Botox are
conducted with the same device without the need of changing
devices during the treatment.
Galvanic Microprotrusion Member
In one embodiment, the microprotrusion member or
microprotrusions of the present invention are made from two
dissimilar metals in contact with each other so that they
form a galvdnic couple, and are therefore capable of
generating a galvanic current when the microprotrusion
member contacts an electrolyte-containing medium. For
example, the microprotrusion member may be made from a thin
zinc sheet, fabricated with the manufacture methods
disclosed in U.S. Patent Nos. 5,983,136, 6,532,386,
6,050,988, or 6,219,574, while another metal (e.g., silver,
silver-silver,chloride, copper, gold) is coated on certain
areas of a microprotrusion member, such as on the s.elected
areas (e.g., the edge) of the skin-contacting surface 6, or
on the microprotrusions 4 (Figure 1).
During a skin treatment, for example, both metals of
the galvanic couple (i.e., zinc and silver-silver chloride)
on the microprotrusion member are in contact with an
electrolyte medium (e.g., a topical composition, a body
fluid such as extracellular fluid, interstitial fluid,
wound exudates, sweat, and pus) and/or the skin to act as a
galvanic cell (e.g., of approximately 1 volt) and to
generate an electric current, going out from the zinc
positive electrode, passing through the electrolyte medium
and/or the skin, and returning into the silver-silver
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chloride negative electrode. This galvanic current may be
used to provide electric stimulation and/or iontophoretic
delivery of active agents into the skin via the
openings/pathways across the skin barrier (i.e., stratum
corneum or epidermis) created by the microprotrusions.
Alternatively, the two metals forming the galvanic couple
may be made to contact the third metal (e.g., titanium, or
stainless steel) from which the microprotrusion member is
made. For example, a zinc layer may be coated onto the
selective areas of a titanium or stainless steel
microprotrusion member by electric plating, electroless
plating, or using a conductive ink including a zinc powder
and a polymer binder. Similarly, a silver-silver chloride
layer may be coated to other areas of a titanium or
stainless steel microprotrusion member. The conductive
metallic microprotrusion member serves as a lead to connect
the galvanic elements zinc and silver-silver chloride. A
galvanic current~ is generated when both galvanic elements
coming into contact with the electrolyte medium and/or the
skin during the device application.
EXAMPLES
Example 1: Microprotrusion Member
Microprotrusion members containing microprotrusion
arrays were produced by photochemical etching and forming
using a controlled manufacturing process as described in
European Patent No. 914,178 B1. The finished arrays were
made of a thi,n sheet of titanium, and had a defined
microprotrusion density of about 725 microprotrusions per
cm2. The microprotrusions had lengths of 145, 185 or 225
microns and had arrow-head-shaped. Fr=om this
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microprotrusion arr'ay sheet, a 5 mm diameter disk was cut
out from such screen using a CO2 laser.
Example 2: Patch
The resulting disks of microprotrusion arrays from
Example 1 were affixed to an adhesive patch composed of a
hydrocolloidal gel and a polyurethane film with sodium
carboxymethyl cellulose adhesive (Band-Aid Advanced Healing
Blister Block, Johnson & Johnson Consumer Products Company,
Skillman, NJ, USA), with the microprotrusions facing away
from the adhesive. The patch had a surface area of about
0.8 cm2 incl~uding the 0.2 cm2 microprotrusion array.
Example 3: Handle Implement
An implement device according to Figures'3-5 was made
using two stainless steel compression springs (e.g.,
McMaster-Carr Supply Co., NJ, USA, Model, Model Gardner
Spring, SS-8M for the first spring, and MC050-0330-M for
second spring). The impact pressure was from about 0.5 to
about 7 lbs/cm2 for facial application. A slightly higher
pressure was used in forearm applications.
Example 4: Enhancement of Active Agent Delivery
The following procedure was used to demonstrate
controlled active agent delivery into skin. The
microprotrusion disk of Example 1 was affixed on the
desired skin site on subject's forearm or face. The
implement of Example 3 was used to push the microprotrusion
disk through stratum corneum with predetermined impact
pressure modified by the choice of spring. The impact
pressure was measured using a digital force meter (Model
DFM 10, Chatillon, Greensboro, NC). The contact area
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between the implement device and skin was determined to be
about 1.2 cm2 in diameter. The pressure per unit area was
calculated from the ratio of pressure/contact area. The
disk was removed immediately after the application. Both
subject sensation (e.g., pain and sting) and erythema of
the testing site were.recorded immediately after the
application, and is reported in Table 1-.
Table 1
TEST MICRO- IMPLEMENT SKIN SENSATION DURING
SUBJECT PROTRUSION DEVICE APPLICATION
/SKIN SITE LENGTH PRESSURE
(MICROMETE (LBS/CMZ)
R) ~
1/Forearm 225 8 Slightly sting
2/Forearm 225 6 Slightly sting
3/Cheek 185 3.2 None
( bone ) '
4/Forearm 185 4.6 None
5/Forearm 185 8 Slightly sting
6/Forehead 145 5 None
The delivery of active agents following treatment
was determined by applying approximately 10 microliters of
0.10% wt/wt histamine (Sigma Aldrich, St. Louis, MO) on
treatment test site. The reaction of the subject's skin to
histamine (e.,g., erythema) was recorded after 10 minutes
following histamine application to the treatment site by
visual inspection. Additional inspection followed if a
reaction was detected at 10 minutes. Controls were run by
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applying histamine solution to untreated skin sites'(e.g.,
sites not pierced by the microprotrusion members). All
test sites were graded visually for the evidence of post-
inflammatory hyperpigmentation (PIH) for up to at least 3
weeks. Table sets forth the results of the study.
Table 2
TEST SUBJECT PRESENCE OF PRESENCE OF ENHANCED
/SKIN SITE ERYTHEMA PIH ACTIVE
IMMEDIATELY DELIVERY
AFTER (HISTAMINE
APPLICATION RESPONSE)
OF DEVICE
1/Forearm Present after Yes Yes,
several hours consistent
2/Forearm Present after Yes Yes,
several hours consistent
3/Cheek No No Yes, but not
(bone) ' consistent
4/Forearm No No Yes,
consistent
5/Forearm Present after Yes Yes,
several hours consistent
6/Forehead No No Yes,
consistent
The skin's reactions to topically applied histamine
following microprotrusion treatment manifested in erythema.
The control te~t sites, however, did not result in
erythema. These results, thus, indicate the microprotrusi.on
member enhanced active agent delivery into the skin.
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Example 5: Facial Application
Conditions and procedures in Example 4 were followed
to determine the tolerance of subjects to the pressure and
size of microprotrusion member when applied to facial skin.
The results of the average pressure above which the users
reported discomfort is reported in Table 3. Test subjects
(n=10) reported substantial discomfort for an impact
pressure above about 7 lbs/cm2 when microprotrusion member
with an area about 1 cm2 was applied to human forehead skin.
Table 3
Location of Pressure (lbs/cm2) Pressure (lbs/cm2)
Contact Applied to 1 cm2 Applied to 2 cm2
Member Member
Forehead 6.2 0.8 3.8 0.8
Cheek (bone) 4.5 0.9 3.5 1.2
Cheek (soft)' 3.6 0.6 2.3 0.6
Example 6: Composition
A composition was prepared using the following
components in Table 4:
Table 4
CHEMICAL NAME % WT/WT
DI water 87.20%
Phenoxyethanol / 1%
parabens '
Disodium EDTA 0.05%
Dimethicone 2%
Glycerin 1.5%
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Soy bean Seed (Soja) 50
Extract
Polyacrylamide/ 3.2%
laureth-7/
isoparaffin
Butylated 0.05%
Hydroxytoluene (BHT)
The composition was prepared as follows: The deionized
water, Phenoxyethanol/parabens, and Disodium EDTA were
mixed until EDTA dissolved. The Dimethicone and Glycerin
were then added and mixed well until dissolved. The
Soybean Seed Extract was then added and mix for ten
minutes. The Polyacrylamide/laureth-7/isoparaffin and BHT
were mixed together in separate beaker and then added to
the aqueous batch.' The mixture was then mixed for
approximately one hour until a homogeneous mixture was
formed. Lastly, the soymilk was homogenized into the
mixture. The~finished product was packaged in 1 oz tubes.
Example 7: Use on Acne Marks
The 185 micron length microprotrusion array disk
described in the Example 1 was applied to an acne dark
marks on the cheek of a subject of Fitzpatrick Skin Type
Vi. A dual-spring implement device described in Example 3
was applied twice onto the microprotrusion patch with an
impact pressure of 4.2 lbs/cm2. The disk was removed and a
pea size of the composition of Example 6 was applied to the
treated spot. The procedure was repeated once every other
day for 21 days (on the days when the microprotrusion disk
was not used, the composition was applied to the treatment
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site). Visible digital photos were taken at baseline and at
week 3. It was found that both the dark color and size of
the acne mark treated were reduced. The acne mark area had
a size reduction of 34% versus baseline.
Example 8 Use on Wrinkles
Skin having wrinkles may also be treated.
Compositions containing anti-wrinkle actives such as
tretinoin (e.g., Renova from Ortho-Neutrogena, Los Angels,
CA), retinol (e.g., Healthy Skin Anti-wrinkle Anti-blemish
Cream from Neutrogena, Los Angels, CA), or nondenatured soy
extract (e.g., Aveeno Positively Radiant Anti-wrinkle-Cream
from Johnson & Johnson Consumer Product Companies,
Skillman, NJ) can be post-applied daily to the
microprotrusions treated skin (e.g., for at least about 4
weeks ) .
Example 9 Use to Treat Acne
A healthy subject of skin type IV (Fitzpatrik scale)
used the microprotrusion patch prepared from
microprotrusion array or membrane described in the Example
1 and the implement of Example 3 to treat a pimple
containing pus. The pimple was raised and has whitehead
characteristics. An impact pressure of 5 lbs/cm2 was
applied by the implement device as in Example 3 to force
the microprotrusions (length = 185 microns) puncturing into
the pimple. After releasing the microprotrusions, pus was
observed to flow outward,from the pimple. A cotton swab
was applied to absorb the pus fluid. The reduction of the
pimple elevation or volume was determined to be - 70%
using a Primos image system (GF Messtechnik GmbH, Berlin,
Germany). An anti-acne topical composition containing
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salicylic acid was applied to the treated pimple. Within
hours, the raised pimple was visually smaller and
flattened. Within 24 hours, the pimple was almost
invisible. The subject was monitored for 30 days. No scar
nor post-inflammatory hyperpigmentation was observed for
the treated acne lesion.
Example 10: Use to treat pimpl2
Eleven healthy subjects of skin type I-IV (Fitzpatrik
scale) appli'ed a microprotrusion patch to a targeted acne
pimple. The microprotrusion patch was prepared from
microprotrugion array or membrane described in the Example
1 and the implement of Example 3 to treat a pimple of size
>2 mm in diameter. An impact pressure of 5 lbs/cm2 was
applied by the implement device to force'the
microprotrusions (length = 225 microns) puncturing into the
pimple. After releasing the microprotrusions, a cotton
swab was applied to absorb any out-flowing pus fluid. An
anti-acne topical composition containing salicylic acid was
applied to the treated pimple after the microprotrusion
application and further applied twice a day for a week.
The subject evaluated the targeted pimple at baseline,
immediately, 24 hours, 48 hours and 168 hours after
microprotrusion application. As reported in Table 5, the
subjects reported both immediate and continuous significant
improvements for pimple size, pimple color (redness),
pimple elevation, pain, severity and appearance.
Table 5
The percentage (%) of subjects saw improvement vs. baseline
after microprotrusion application (n=11).
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ppearance Size Raise Pain Redness Severit
Immediate 82% 64% 73% 901o 73 0= 73%
Day 1 100% 100% 100% 1000 100% 91%
Day 2 100% 100% 100% 100% 100o 100%
Day 7 100% 100% 100% 100% 100% 100%
Example 11: Compressible Cover Device
A compressible cover device was produced by modifying a
lancet (BD Ultra-fin(ETM 33 available from Becton, Dickinson
and Company, Franklin Lakes, NJ) having 33 Gauge stainless
steel needle with a length of 1/8" and 0.07" diameter. The
needle was coverediwith a compressible cover made of an
elastic polymer (GE Silicone II, 100% white silicone
sealant, GE Sealants and Adhesives, Huntersville, NC
28078). Additionally, a thin layer of absorbing material
made from low density polyethylene (Super Brush, Chicopee,
MA) was placed on top of the elaeti,c polymer. The device
can be sterilized, such as by use of gamma irradiation
(e.g. > 25 kGy).
Example 12: Pimple extraction + topical (anti-acne film
forming formula
A subject of skin type IV used the microneedle device
described in Example 10 to treat a pimple near the nose.
The pimple had a size of about 2.5 mm diameter. Before the
use of the device, the pimple was raised and had pustule
acne characteristics. After using microneedle to pierce the
pimple, pus was observed to flow outward from the pimple
and absorbed by the absorbing sheet. An immediate pimple
height reduction was observed. An anti-acne topical
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composition containing salicylic-acid was applied to the
treated pimple for twice daily. After twenty-four (24)
hours, the pimple was almost.invi,sible to the subject.
Furthermore, no signs of PIH or scaring were seen
following continuous monitoring of the test site for 3
weeks following the treatment.
It is understood that while the invention has been
described in conjunction with the detailed description
thereof, that the foregoing description is intended to
illustrate and not limit the scope of the invention, which
is defined by the 'scope of the appended claims. Other
aspects, advantages, and modifications are within the
claims.
What is claimed is:
