U.S. patent application number 17/502493 was filed with the patent office on 2022-06-09 for needling device and drug applicator.
The applicant listed for this patent is Follica, Inc.. Invention is credited to David Chastain, Daniel DeRuntz, Anthony Vincent Dibella, Joseph Gordon, Scott Kellogg, Justin David Morse, Jason Robinson, Nathan Rollins, Daniel P. Smith, Alex Staudt, David C. Tharp, Greg Wolos.
Application Number | 20220176094 17/502493 |
Document ID | / |
Family ID | 1000006164769 |
Filed Date | 2022-06-09 |
United States Patent
Application |
20220176094 |
Kind Code |
A1 |
Tharp; David C. ; et
al. |
June 9, 2022 |
NEEDLING DEVICE AND DRUG APPLICATOR
Abstract
A needling device may be used for needling of a subject's skin,
and a drug applicator device may be used for applying a drug to a
subject's skin. For example, a needling device may be applied to a
subject's skin for hair growth applications, or may be used for
wrinkle, scar, or tattoo removal. A drug applicator device may be
used for multiple drug application purposes such as applying a hair
growth compound to the skin of a subject.
Inventors: |
Tharp; David C.; (Boston,
MA) ; Kellogg; Scott; (Mattapoisett, MA) ;
DeRuntz; Daniel; (Somerville, MA) ; Robinson;
Jason; (Tewksbury, MA) ; Wolos; Greg;
(Cambridge, MA) ; Staudt; Alex; (Cambridge,
MA) ; Chastain; David; (Boston, MA) ; Smith;
Daniel P.; (Portsmouth, RI) ; Morse; Justin
David; (Cranston, RI) ; Dibella; Anthony Vincent;
(Franklin, MA) ; Gordon; Joseph; (Mansfield,
MA) ; Rollins; Nathan; (Boylston, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Follica, Inc. |
Boston |
MA |
US |
|
|
Family ID: |
1000006164769 |
Appl. No.: |
17/502493 |
Filed: |
October 15, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15763682 |
Mar 27, 2018 |
11185672 |
|
|
PCT/US16/53972 |
Sep 27, 2016 |
|
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17502493 |
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62233373 |
Sep 27, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 2017/00747
20130101; A61M 35/003 20130101; A61M 37/0015 20130101; A61B
2017/00398 20130101; A61B 17/205 20130101; A61B 2017/00734
20130101; A61M 5/32 20130101; A61H 2205/021 20130101; A61B
2017/00752 20130101; A61M 2037/0023 20130101; A61B 2017/00761
20130101; A61B 2017/00769 20130101; A61B 2090/0813 20160201; A61B
17/20 20130101; A61B 90/30 20160201 |
International
Class: |
A61M 37/00 20060101
A61M037/00; A61M 35/00 20060101 A61M035/00; A61B 17/20 20060101
A61B017/20; A61M 5/32 20060101 A61M005/32 |
Claims
1.-24. (canceled)
25. A needling device, comprising: a sheath assembly comprising a
needle array; and a main unit comprising a motor for driving the
needle array, wherein the needle array comprises a rectangular base
and two substantially parallel rows of needles on the rectangular
base; wherein the needles of a first row are offset from the
needles of a second row so that a needle on the first row is
horizontally displaced from two needles on the second row.
26.-64. (canceled)
65. The needling device of claim 25, wherein the main unit is
configured to be fully encapsulated within the sheath assembly so
that all parts of the main unit are protected from the outside
environment, characterized in that the sheath assembly further
comprises a sheath cap, wherein the sheath cap is removable for
inserting or removing the main unit.
66. The needling device of claim 25, wherein the internal
components of the sheath assembly include a bio-barrier as a layer
of protection and sealing of the main unit, and a drive shaft
interface that is connected to the needles of the needle array and
removably attachable to a drive shaft of the needling device.
67. The needling device of claim 25, wherein (i) the base is
rectangular; and/or (ii) the array comprises three or more rows;
and/or (iii) the needles of a first row are offset from the needles
of a second row such that a needle on the first row is horizontally
between and equidistant from two needles on the second row.
68. The needling device of claim 66, wherein the needles of the
needle array are arranged on a needle holder that is secured to the
drive shaft interface.
69. The needling device of claim 68, wherein the bio-barrier is
securely attached about the needle holder, and wherein the
bio-barrier is configured to move axially with the needle
holder.
70. The needling device of claim 25, (i) wherein the needle array
is driven axially by the motor in a direction that is parallel with
a longitudinal axis of the needling device along which the needling
device extends, (ii) the needling device is adapted to perform
needling of a human scalp for promoting hair growth, of skin tissue
for skin repair, or of scar tissue for scar removal, wherein
preferably the needling device is adapted to treat baldness or
chemotherapy-induced alopecia; or (iii) the needling device is
adapted to disrupt a basal or suprabasal epidermal layer of a human
skin.
71. The needling device of claim 65, wherein the sheath assembly
keeps the main unit substantially germ free, sterile, or free from
biological contamination as a result of fully encapsulating the
main unit.
72. The needling device of claim 65, wherein the main unit further
comprises a main unit cap and the sheath cap is configured to
rotate the main unit cap.
73. The needling device of claim 65, wherein the sheath cap is
configured to control a depth of the needle array without removing
the fully encapsulated main unit from within the sheath assembly,
wherein the depth of the needle array ranges from a depth extending
beyond an end of the sheath assembly and towards a subject's skin
to a depth that is fully retracted within the sheath assembly and
away from the subject's skin.
74. The needling device of claim 25, wherein the needling device
further comprises one or more buttons for controlling the needling
device positioned on a surface of the sheath assembly without
removing the fully encapsulated main unit from within the sheath
assembly.
75. The needling device of claim 74, wherein the one or more
buttons are configured to control one or more of a depth of the
needle array, a speed of needling, a power of the needling device,
and a LED for illumination of a perturbation area.
76. The needling device of claim 25, wherein: the main unit further
comprises a main unit cap and a drive shuttle chassis for
controlling a depth of the needle array, and in response to a user
rotating the sheath cap, the main unit cap is rotated, the drive
shuttle chassis is axially displaced, and the depth of the needle
array is adjusted; and/or the needle array comprises a rectangular
base.
77. The needling device of claim 76, wherein the needling device
eliminates dragging of needles in a subject's skin.
78. The needling device of claim 25, wherein the main unit further
comprises a drive shaft interface that is configured to contact the
needle array for controlling needling.
79. The needling device of claim 78, wherein the main unit further
comprises a drive cam and the drive cam is attached to the drive
shaft interface for actively controlling a positive and return
motion of the needle array, the positive motion being towards a
skin of a subject and the return motion being away from the skin of
the subject and towards the needling device.
80. The needling device of claim 79, wherein (i) the needling
device is configured to eliminate vibration to reduce fatigue to a
user's hand while operating the needling device, or (ii) the drive
cam comprises a slot that retains a pin attached to the drive shaft
for reducing a vibration of the needle array.
81. The needling device of claim 25, wherein the main unit further
comprises a drive cam that is attached to the motor for controlling
a positive and return motion of needling, the positive motion being
towards a skin of a subject and the return motion being away from
the skin of the subject and towards the needling device.
82. The needling device of claim 25, wherein (i) the needling
device further comprises a means for emitting infrared rays,
wherein follicles of a subject's scalp can be stimulated using both
the needle array and the emitted infrared rays, or (ii) the
needling device further comprises a light for illuminating a target
region on a subject's skin.
83. The needling device of claim 25, wherein needle array is
configured so as to provide for a quicker and more efficient
needling operation in contrast to a rounded arrangement of needles
or a circular needle array.
Description
1. CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application
Ser. No. 15/763,682, filed Sep. 27, 2016, which is a national stage
of International Patent Application No. PCT/US2016/053972, filed
Sep. 27, 2016, which claims the benefit of U.S. Provisional
Application No. 62/233,373, filed on Sep. 27, 2015, each of which
is incorporated herein by reference in its entirety for all
purposes.
2. BACKGROUND OF THE INVENTION
2.1 Field of the Invention
[0002] The following description relates to a needling device for
needling of a subject's skin by a user such as a physician or any
user, and a fluid or drug dispensing applicator device for
massaging and applying a fluid or drug to a subject's skin. In
certain embodiments, the subject is in need of inducing hair growth
or hair follicle neogenesis, is need of preventing hair loss,
and/or is a subject as described in Section 5.5. For example, a
needling device may be applied to a subject's skin for hair growth
applications, or may also be used for wrinkle reduction, scar
revision, hair removal, tattoo removal, and pigmentation. The fluid
or drug applicator device may be used for multiple drug application
purposes such as applying a hair growth compound to the skin of a
subject or treatment for other dermatological conditions.
2.2 Description of Related Art
[0003] Needling devices are typically used for tattoo removal or
wrinkle reduction mechanisms by lightly penetrating a subject's
skin without penetrating deeper areas of a subject's skin or scalp.
A conventional needling device does not allow a user to easily
interchange needling adapters, and maintain the sterility of the
combined device. A conventional device must also be sterilized by a
physician, a user, or a clinic prior to use. Further, a
conventional needling device provides a set of needles that does
not allow uniform needling, and interchangeability and versatility
of a device. In addition, conventional needling arrays are provided
in configurations that do not allow a user or operator to clearly
view a target area while performing the needling operation.
[0004] Examples of conventional drug applicators, such as the
applicator described in U.S. Patent Application Publication No.
2008/0161737 to Hilditch, allow the manual dispensing of a drug and
include a massage head. However, such devices are not programmable,
do not allow a user or physician to program the device to
automatically follow a preset procedure, and do not provide easy
replacement or refilling of the drug to be dispensed. Thus, a
device that provides programmable massaging and drug dispensing
operations, and ease of replacement and refilling of the liquid or
drug to be dispensed, is needed.
3. SUMMARY
[0005] In an aspect, a needling device includes a sheath assembly
having a needle array and a main unit comprising a motor for
driving the needle array, where the main unit is configured to be
fully encapsulated within the sheath assembly so that all parts of
the main unit are protected from the outside environment. In a
specific embodiment, the needle array is driven axially by the
motor in a direction that is parallel with a longitudinal axis of
the needling device along which the needling device extends. In a
specific embodiment, the needling device is adapted to perform
needling of a human scalp for promoting hair growth, of skin tissue
for skin repair, or of scar tissue for scar removal. In a specific
embodiment, the needling device is adapted to treat baldness or
chemotherapy-induced alopecia. In a specific embodiment, the
needling device is adapted to disrupt a basal or suprabasal
epidermal layer of a human skin. In a specific embodiment, the
sheath assembly keeps the main unit substantially germ free,
sterile, or free from biological contamination as a result of fully
encapsulating the main unit. In a specific embodiment, the needling
device further comprises a bio-barrier within the sheath assembly
to prevent contamination from a subject's blood. In a specific
embodiment, the sheath assembly further comprises a sheath cap. In
a specific embodiment, the sheath cap is removable for inserting or
removing the main unit. In a specific embodiment, the sheath cap is
configured to control a depth of the needle array without removing
the fully encapsulated main unit from within the sheath assembly.
In a specific embodiment, the depth of the needle array ranges from
a depth extending beyond an end of the sheath assembly and towards
a subject's skin to a depth that is fully retracted within the
sheath assembly and away from the subject's skin. In a specific
embodiment, the main unit further comprises a main unit cap and the
sheath cap is configured to rotate the main unit cap. In a specific
embodiment, the needling device further comprises one or more
buttons for controlling the needling device positioned on a surface
of the sheath assembly without removing the fully encapsulated main
unit from within the sheath assembly. In a specific embodiment, the
one or more buttons are configured to control one or more of a
depth of skin penetration of the needle array, a speed of needling,
a power of the needling device, and a LED for illumination of a
perturbation area. In a specific embodiment, the main unit further
comprises a main unit cap and a drive shuttle chassis for
controlling a depth of the needle array, the sheath assembly
further comprises a sheath cap, and in response to a user rotating
the sheath cap, the main unit cap is rotated, the drive shuttle
chassis is axially displaced, and the depth of the penetration of
the needle array is adjusted. In a specific embodiment, the
needling device eliminates dragging of needles in a subject's skin.
In a specific embodiment, the needle array comprises a rectangular
base and two substantially parallel rows of needles on the
rectangular base so that a speed of needling is increased and a
number of needling strokes is reduced. In a specific embodiment,
the main unit further comprises a drive shaft that is configured to
contact the needle array for controlling needling. In a specific
embodiment, the main unit further comprises a drive element and the
drive element is attached to the drive shaft for actively
controlling a positive and return motion of the needle array, the
positive motion being towards a skin of a subject and the return
motion being away from the skin of the subject and towards the
needling device. In a specific embodiment, the needling device is
configured to eliminate vibration to reduce fatigue to a user's
hand while operating the needling device. In a specific embodiment,
the main unit further comprises a drive element that is attached to
the motor for controlling a positive and return motion of needling,
the positive motion being towards a skin of a subject and the
return motion being away from the skin of the subject and towards
the needling device. In a specific embodiment, the needling device
further comprises a means for emitting infrared rays, wherein
follicles of a subject's scalp can be stimulated using both the
needle array and the emitted infrared rays. In a specific
embodiment, the needling device further comprises a light for
illuminating a target region on a subject's skin.
[0006] In another aspect, a needling device includes a sheath
assembly having a needle array and a main unit having a motor for
driving the needle array in a controlled manner, where the needle
array includes a rectangular base and two substantially parallel
rows of needles on the rectangular base so that a speed of needling
is increased and a number of needling strokes is reduced.
[0007] In yet another aspect, a needling device includes a sheath
assembly having a needle array, and a main unit having a motor for
driving the needle array, where the main unit further includes a
main unit cap and a drive shuttle chassis for controlling a depth
penetration of the needle array, the sheath assembly further
includes a sheath cap, and in response to a user rotating the
sheath cap, the main unit cap is rotated, the drive shuttle chassis
is axially displaced, and the depth of penetration of the needle
array in the skin is adjusted.
[0008] In an additional aspect, a needling device includes a sheath
assembly having a needle array and a main unit having a motor for
driving the needle array, where the main unit further includes a
drive shaft that is configured to contact the needle array for
controlling needling. and a drive element, and where the drive
element is attached to the drive shaft for actively controlling a
positive and return motion of the needle array, the positive motion
being towards a skin of a subject and the return motion being away
from the skin of the subject and towards the needling device.
[0009] In another additional aspect, a method of using a needling
device for stimulating hair growth includes providing a needling
device having a sheath assembly having a needle array and a main
unit having a motor for driving the needle array, opening the
sheath assembly and placing the main unit within the sheath
assembly so that the main unit is fully encapsulated and protected
from the outside environment, and powering on the needling device.
In a specific embodiment wherein the sheath assembly comprises a
needle array, the method further comprises
[0010] removing the sheath assembly; and replacing the sheath
assembly with another sheath assembly comprising another needle
array.
[0011] In yet another additional aspect, a method of using a
needling device and a drug applicator for stimulating hair growth
includes providing a needling device including a sheath assembly
having a needle array and a main unit having a motor for driving
the needle array, providing a drug applicator for drug delivery and
massaging including a housing, a drug delivery cartridge carried by
the housing, a massage head which is mounted on the housing for
massaging a subject's skin, using the needling device to perform
targeted cutaneous perturbation for disrupting a layer of a human
scalp, after using the needling device, using the drug applicator
for applying a drug to the disrupted area of the human scalp. In a
specific embodiment, the disrupted layer of the human scalp is the
basal or suprabasal epidermal layer, and the drug that is applied
is minoxidil or a proteasome inhibitor including lactacystin, a
peptidyl aldehyde, or pentoxyfilline (PTX). In a specific
embodiment, the method further comprises delivering the drug
directly to the human scalp to facilitate transdermal transport. In
a specific embodiment, the method further comprises massaging the
drug that is delivered to the human scalp to evenly spread the
drug.
[0012] In a further aspect, an applicator for drug delivery and
massaging includes a housing, a drug delivery cartridge, and a
massage head mounted on the housing, where the drug delivery
cartridge is configured to dispense a drug automatically by a
dispensing mechanism that is linked to movement of the massage
head. In a specific embodiment, the applicator is configured to
stretch or massage a subject's skin while simultaneously dispensing
the drug. In a specific embodiment, an amount of drug being
dispensed can be controlled by controlling a number of massaging
strokes per massaging cycle, a stroke distance per massaging cycle,
or a profile of the dispensing mechanism. In a specific embodiment,
the drug that is applied is minoxidil or a proteasome inhibitor
including lactacystin, a peptidyl aldehyde, or pentoxyfilline
(PTX). In a specific embodiment, the drug delivery cartridge and
the massage head are attached and configured to be removed and
replaced simultaneously by a user. In a specific embodiment, the
massage head comprises a rigid disc and an elastic massaging
element. In a specific embodiment, a speed of the movement of the
massage head and a frequency of the massaging effect is adjustable
by the user. In a specific embodiment, the adjustable frequency of
the massaging effect comprises 1 Hertz, 2 Hertz, and 4 Hertz. In a
specific embodiment, the applicator further comprises a controller
and a sensor that are configured to detect a rotation angle of the
massage head to determine a dispensed dosage using the detected
angle. In a specific embodiment, the applicator is operable in a
massage-only or a massage-and-dispense mode. In a specific
embodiment, a rotation angle of the massage head controls whether
the applicator is in the massage-only mode or the
massage-and-dispense mode. In a specific embodiment, the applicator
further comprises a keypad positioned on a surface of the
applicator. In a specific embodiment, the applicator further
comprises an LED and a control unit configured to operate the LED
in response to determining that a next dose is due. In a specific
embodiment, the applicator further comprises an inductive charging
base configured to receive the housing for charging the applicator.
In a specific embodiment, the applicator further comprises a light
for illuminating a target region of the user's skin.
[0013] In a further aspect, an applicator for drug delivery and
massaging includes a housing, a drug delivery cartridge carried by
the housing for dispensing a drug, a massage head which is mounted
on the housing for massaging a subject's skin, a cam drive which is
mounted in the housing and rotates the drug delivery cartridge and
the massage head for providing a massaging effect, and a controller
and sensors that are configured to detect a rotation angle of the
massage head to determine a dispensed dosage using the detected
angle. In a specific embodiment, the drug delivery cartridge and
massage head are attached and configured to be removed and replaced
simultaneously by a user. In a specific embodiment, the massage
head comprises a rigid disc and an elastic massaging element. In a
specific embodiment, a speed of the rotation of the massage head
and a frequency of the massaging effect is adjustable by the user.
In a specific embodiment, the adjustable frequency of the massaging
effect comprises 1 Hertz, 2 Hertz, and 4 Hertz. In a specific
embodiment, the applicator is operable in a massage-only or a
massage-and-dispense mode. In a specific embodiment, a rotation
angle of the massage head controls whether the applicator is in the
massage-only or the massage-and-dispense operation. In a specific
embodiment, the applicator further comprises a keypad positioned on
a surface of the applicator. In a specific embodiment, the
applicator further comprises an LED and a control unit configured
to operate the LED in response to determining that a next dose is
due. In a specific embodiment, the applicator further comprises an
inductive charging base configured to receive the housing for
charging the applicator.
[0014] In a further aspect, a method of using an applicator for
hair growth applications includes providing an applicator including
a housing, a drug delivery cartridge carried by the housing, and a
massage head which is mounted on the housing, powering on the
applicator, and dispensing a drug automatically by a dispensing
mechanism that is linked to movement of the massage head. In a
specific embodiment, the drug that is applied is minoxidil or a
proteasome inhibitor including lactacystin, a peptidyl aldehyde, or
pentoxyfilline (PTX). In a specific embodiment, the method of using
the applicator further comprises controlling the applicator
remotely. In a specific embodiment, the method of using the
applicator further comprises receiving notifications from and
interacting with the applicator using a remote user interface. In a
specific embodiment, the remote user interface is a mobile
application that is configured to communicate with a user in order
to facilitate compliance with set parameters.
4. BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0015] The foregoing summary, as well as the following detailed
description, will be better understood when read in conjunction
with the appended drawings. For the purpose of illustration, there
is shown in the drawings certain embodiments of the present
disclosure. It should be understood, however, that the invention is
not limited to the precise arrangements and instrumentalities
shown. The accompanying drawings, which are incorporated in and
constitute a part of this specification, illustrate an
implementation of systems and apparatuses consistent with the
present invention and, together with the description, serve to
explain advantages and principles consistent with the
invention.
[0016] FIG. 1 is a right side perspective view illustrating an
example of a needling device. FIG. 1A is an exploded view
illustrating an example of a needling device.
[0017] FIG. 2 is a left side perspective view illustrating an
example of a needling device.
[0018] FIG. 3 is a right side elevational view illustrating an
example of a needling device.
[0019] FIG. 4 is a left side elevational view illustrating an
example of a needling device.
[0020] FIG. 5 is a top side elevational view illustrating an
example of a needling device.
[0021] FIG. 6 is a bottom side elevational view illustrating an
example of a needling device.
[0022] FIG. 7 is a top end elevational view illustrating an example
of a needling device.
[0023] FIG. 8 is a bottom end elevational view illustrating an
example of a needling device.
[0024] FIG. 9 is a right side perspective view illustrating an
example of a needling device with a needling adaptor. FIG. 9A is a
side view of an example of a needling device. FIGS. 9B, 9C, and 9D
are diagrams illustrating sectional views of the needling device
with a needling adaptor in FIG. 9A.
[0025] FIG. 10 is a left side perspective view illustrating an
example of a needling device with a needling adaptor.
[0026] FIG. 11 is a right side elevational view illustrating an
example of a needling device with a needling adaptor.
[0027] FIG. 12 is a left side elevational view illustrating an
example of a needling device with a needling adaptor.
[0028] FIG. 13 is a top side elevational view illustrating an
example of a needling device with a needling adaptor.
[0029] FIG. 14 is a bottom side elevational view illustrating an
example of a needling device with a needling adaptor.
[0030] FIG. 15 is a top end elevational view illustrating an
example of a needling device with a needling adaptor.
[0031] FIG. 16 is a bottom end elevational view illustrating an
example of a needling device with a needling adaptor.
[0032] FIG. 17 is a right side perspective view illustrating an
example of a needling adaptor for a needling device.
[0033] FIG. 18 is a left side perspective view illustrating an
example of a needling adaptor for a needling device.
[0034] FIG. 19 is a right side elevational view illustrating an
example of a needling adaptor for a needling device.
[0035] FIG. 20 is a left side elevational view illustrating an
example of a needling adaptor for a needling device.
[0036] FIG. 21 is a top side elevational view illustrating an
example of a needling adaptor for a needling device.
[0037] FIG. 22 is a bottom side elevational view illustrating an
example of a needling adaptor for a needling device.
[0038] FIG. 23 is a top end elevational view illustrating an
example of a needling adaptor for a needling device.
[0039] FIG. 24 is a bottom end elevational view illustrating an
example of a needling adaptor for a needling device.
[0040] FIG. 25 is a right side perspective view illustrating an
example of a needling device with a charging station. FIG. 25A is a
side view of an example of a needling device with a charging
station. FIGS. 25B and 25C are diagrams illustrating sectional
views along the lines illustrated in FIG. 25A.
[0041] FIG. 26 is a left side perspective view illustrating an
example of a needling device with a charging station.
[0042] FIG. 27 is a right side elevational view illustrating an
example of a needling device with a charging station.
[0043] FIG. 28 is a left side elevational view illustrating an
example of a needling device with a charging station.
[0044] FIG. 29 is a top side elevational view illustrating an
example of a needling device with a charging station.
[0045] FIG. 30 is a bottom side elevational view illustrating an
example of a needling device with a charging station.
[0046] FIG. 31 is a top end elevational view illustrating an
example of a needling device with a charging station.
[0047] FIG. 32 is a bottom end elevational view illustrating an
example of a needling device with a charging station.
[0048] FIG. 33 is a right side perspective view illustrating an
example of a charging station for a needling device.
[0049] FIG. 34 is a left side perspective view illustrating an
example of a charging station for a needling device.
[0050] FIG. 35 is a right side elevational view illustrating an
example of a charging station for a needling device.
[0051] FIG. 36 is a left side elevational view illustrating an
example of a charging station for a needling device.
[0052] FIG. 37 is a top side elevational view illustrating an
example of a charging station for a needling device.
[0053] FIG. 38 is a bottom side elevational view illustrating an
example of a charging station for a needling device.
[0054] FIG. 39 is a top end elevational view illustrating an
example of a charging station for a needling device.
[0055] FIG. 40 is a bottom end elevational view illustrating an
example of a charging station for a needling device.
[0056] FIG. 41 is a right side perspective view illustrating an
example of a drug applicator with a massage head.
[0057] FIG. 42 is a left side perspective view illustrating an
example of a drug applicator with a massage head.
[0058] FIG. 43 is a right side elevational view illustrating an
example of a drug applicator with a massage head.
[0059] FIG. 44 is a left side elevational view illustrating an
example of a drug applicator with a massage head.
[0060] FIG. 45 is a top side elevational view illustrating an
example of a drug applicator with a massage head.
[0061] FIG. 46 is a bottom side elevational view illustrating an
example of a drug applicator with a massage head.
[0062] FIG. 47 is a top end elevational view illustrating an
example of a drug applicator with a massage head.
[0063] FIG. 48 is a bottom end elevational view illustrating an
example of a drug applicator with a massage head.
[0064] FIG. 49 is a right side perspective view illustrating an
example of a drug applicator with a charging station.
[0065] FIG. 50 is a left side perspective view illustrating an
example of a drug applicator with a charging station.
[0066] FIG. 51 is a right side elevational view illustrating an
example of a drug applicator with a charging station.
[0067] FIG. 52 is a left side elevational view illustrating an
example of a drug applicator with a charging station.
[0068] FIG. 53 is a top side elevational view illustrating an
example of a drug applicator with a charging station.
[0069] FIG. 54 is a bottom side elevational view illustrating an
example of a drug applicator with a charging station.
[0070] FIG. 55 is a top end elevational view illustrating an
example of a drug applicator with a charging station.
[0071] FIG. 56 is a bottom end elevational view illustrating an
example of a drug applicator with a charging station.
[0072] FIG. 57 is a right side perspective view illustrating an
example of a charging station for a drug applicator.
[0073] FIG. 58 is a left side perspective view illustrating an
example of a charging station for a drug applicator.
[0074] FIG. 59 is a right side elevational view illustrating an
example of a charging station for a drug applicator.
[0075] FIG. 60 is a left side elevational view illustrating an
example of a charging station for a drug applicator.
[0076] FIG. 61 is a top side elevational view illustrating an
example of a charging station for a drug applicator.
[0077] FIG. 62 is a bottom side elevational view illustrating an
example of a charging station for a drug applicator.
[0078] FIG. 63 is a top end elevational view illustrating an
example of a charging station for a drug applicator.
[0079] FIG. 64 is a bottom end elevational view illustrating an
example of a charging station for a drug applicator.
[0080] FIG. 65 is a right side perspective view illustrating an
example of a massage head for a drug applicator.
[0081] FIG. 66 is a left side perspective view illustrating an
example of a massage head for a drug applicator.
[0082] FIG. 67 is a right side elevational view illustrating an
example of a massage head for a drug applicator.
[0083] FIG. 68 is a left side elevational view illustrating an
example of a massage head for a drug applicator.
[0084] FIG. 69 is a top side elevational view illustrating an
example of a massage head for a drug applicator.
[0085] FIG. 70 is a bottom side elevational view illustrating an
example of a massage head for a drug applicator.
[0086] FIG. 71 is a top end elevational view illustrating an
example of a massage head for a drug applicator.
[0087] FIG. 72 is a bottom end elevational view illustrating an
example of a massage head for a drug applicator.
[0088] FIG. 73 is a right side perspective view illustrating an
example of another massage head for a drug applicator.
[0089] FIG. 74 is a left side perspective view illustrating an
example of another massage head for a drug applicator.
[0090] FIG. 75 is a right side elevational view illustrating an
example of another massage head for a drug applicator.
[0091] FIG. 76 is a left side elevational view illustrating an
example of another massage head for a drug applicator.
[0092] FIG. 77 is a top side elevational view illustrating an
example of another massage head for a drug applicator.
[0093] FIG. 78 is a bottom side elevational view illustrating an
example of another massage head for a drug applicator.
[0094] FIG. 79 is a top end elevational view illustrating an
example of another massage head for a drug applicator.
[0095] FIG. 80 is a bottom end elevational view illustrating an
example of another massage head for a drug applicator.
[0096] FIG. 81 is a right side perspective view illustrating an
example of yet another massage head for a drug applicator.
[0097] FIG. 82 is a left side perspective view illustrating an
example of yet another massage head for a drug applicator.
[0098] FIG. 83 is a right side elevational view illustrating an
example of yet another massage head for a drug applicator.
[0099] FIG. 84 is a left side elevational view illustrating an
example of yet another massage head for a drug applicator.
[0100] FIG. 85 is a top side elevational view illustrating an
example of yet another massage head for a drug applicator.
[0101] FIG. 86 is a bottom side elevational view illustrating an
example of yet another massage head for a drug applicator.
[0102] FIG. 87 is a top end elevational view illustrating an
example of yet another massage head for a drug applicator.
[0103] FIG. 88 is a bottom end elevational view illustrating an
example of yet another massage head for a drug applicator.
[0104] FIG. 89 is a diagram illustrating an example of an exploded
view of the drug applicator, massage head, and charging
station.
[0105] FIG. 90 is a diagram illustrating an example of an exploded
cross-sectional view of the drug applicator, massage head, and
charging station.
[0106] FIG. 91 is a diagram illustrating an example of a
cross-sectional view of the drug applicator, massage head, and
charging station.
[0107] FIG. 92 is a diagram illustrating an example of an exploded
three dimensional cross-section of the drug applicator, massage
head, and charging station.
[0108] FIG. 93 is a diagram illustrating an example of a
cross-sectional view of the drug applicator, massage head, and
charging station.
[0109] FIG. 94 is a diagram illustrating alternative designs for
the removable fluid cartridge of the drug applicator.
[0110] FIG. 95 is a diagram illustrating a perspective view of
another example of a needling device enclosed within a needling
adaptor.
[0111] FIG. 96 is a diagram illustrating an exploded view of
another example of a needling device enclosed within needling
adaptor.
[0112] FIG. 97 is a diagram illustrating a cross-sectional view of
another example of a needling device enclosed within a needling
adaptor.
[0113] FIG. 98 is a diagram illustrating a perspective view of the
inner components of another example of a needling device.
[0114] FIG. 99 is a diagram illustrating a magnified view of the
inner components of another example of a needling device.
[0115] FIG. 100 is a diagram illustrating an exploded view of the
inner components of another example of a needling device.
[0116] FIG. 101 is a diagram illustrating a magnified view of the
cross-section of another example of a needling device enclosed
within a needling adaptor.
[0117] FIG. 102 is a diagram illustrating a cross-sectional view of
another example of a needling adaptor.
[0118] FIG. 103 is a diagram illustrating a perspective view of an
example of a needle array.
[0119] FIG. 104 is a diagram illustrating a side elevation view of
an example of a needle array.
[0120] FIG. 105 is a diagram illustrating a bottom end elevation
view of an example of a needle array.
[0121] FIG. 106 is a diagram illustrating a perspective view of
another example of a drug applicator with a massage head and a
charging station.
[0122] FIG. 107 is a diagram illustrating a cross-sectional view of
another example of a drug applicator with a massage head and a
charging station.
[0123] FIG. 108 is a diagram illustrating a cross-sectional view of
another example of a drug applicator.
[0124] FIG. 109 is a diagram illustrating a magnified perspective
view of the inner components of another example of a drug
applicator.
[0125] FIG. 110 is a diagram illustrating a cross-sectional view of
an example of a cartridge for use with a drug applicator.
[0126] FIG. 111 is a diagram illustrating a perspective view of an
example of a cartridge for use with a drug applicator.
[0127] FIG. 112 is a diagram illustrating a perspective view of an
example of a cam for use with a drug applicator.
[0128] FIG. 113 is a diagram illustrating a cross-sectional view of
another example of a drug applicator with a massage head.
[0129] FIG. 114 is a diagram illustrating a magnified view of an
example of an attachment between a drug applicator, a cartridge of
the drug applicator, and a massage head of the drug applicator.
[0130] FIG. 115 is a diagram illustrating a bottom perspective view
of another example of a massage head for use with the drug
applicator.
[0131] FIG. 116 is a diagram illustrating a top perspective view of
another example of a massage head for use with the drug
applicator.
5. DETAILED DESCRIPTION OF THE INVENTION
[0132] Before explaining at least one embodiment of the invention
in detail, it is to be understood that the invention is not limited
in its application to the details of construction and to the
arrangements of the components set forth in the following
description or illustrated in the drawings. The Figures and written
description are provided to teach any person skilled in the art to
make and use the inventions for which patent protection is sought.
The invention is capable of other embodiments and of being
practiced and carried out in various ways. Those skilled in the art
will appreciate that not all features of a commercial embodiment
are shown for the sake of clarity and understanding. Persons of
skill in the art will also appreciate that the development of an
actual commercial embodiment incorporating aspects of the present
inventions will require numerous implementation--specific decisions
to achieve the developer's ultimate goal for the commercial
embodiment. While these efforts may be complex and time-consuming,
these efforts nevertheless would be a routine undertaking for those
of skill in the art having the benefit of this disclosure.
[0133] In addition, it is to be understood that the phraseology and
terminology employed herein are for the purpose of description and
should not be regarded as limiting. For example, the use of a
singular term, such as, "a" is not intended as limiting of the
number of items. Also the use of relational terms, such as but not
limited to, "top," "bottom," "left," "right," "upper," "lower,"
"down," "up," "side," are used in the description for clarity in
specific reference to the Figures and are not intended to limit the
scope of the invention or the appended claims. Further, it should
be understood that any one of the features of the invention may be
used separately or in combination with other features. Other
systems, methods, features, and advantages of the invention will be
or become apparent to one with skill in the art upon examination of
the Figures and the detailed description. It is intended that all
such additional systems, methods, features, and advantages be
included within this description, be within the scope of the
present invention, and be protected by the accompanying claims.
5.1 Needling Devices
[0134] Needling devices described herein may be used for a number
of different procedures including hair growth applications, wrinkle
reduction, scar revision, hair removal, tattoo removal, and
pigmentation. Advantages of the needling devices described this
application include protecting a reusable main unit or needling
device having a removable sheath or adaptor to provide ease of use
by a patient or physician in performing needling operations for a
number of different procedures. Methods of using the needling
devices described in this application are provided in more detail
in Section 5.4, below.
5.1.1 Illustrative Embodiments of the Needling Device
[0135] Referring to FIG. 1 by way of non-limiting example, and
consistent with embodiments of the invention, a needling device
100, which in some embodiments may be a micropen 100 used for
micro-needling, includes a body 110, a power interface 111,
charging contacts 112, a first dial 113 for needle adjustment
including a first measurement indicator 114, a second dial 115 for
needle adjustment including a second measurement indicator 116, and
a light pipe 117 for illuminating a light path in a direction
parallel to the longitudinal axis of the micropen 100.
[0136] In an example, the micropen body 110 is made from an
aluminum material with an anodized black or anodized satin finish,
but is not limited thereto. The shape and contour of the micropen
body 110, also the shape of the micropen body 110 as used in
conjunction with the adaptor 200 discussed below, allows for a user
to obtain improved control and handling of the micropen 100 during
micro-needling operations.
[0137] Referring to FIG. 1A, the micropen 100 is used with a
corresponding needling adaptor 200 that includes an adaptor body
210, a power interface 211, a micropen connection section 212, a
lower body 213, a needling head 214, a head covering 215, and a
number of needles 216 on the needling head 214. The adaptor 200 may
be formed from a variety of different materials. In an example, the
adaptor 200 is formed from a polycarbonate or other plastic
material. The needles 216 may also be formed from a variety of
different materials, and an example includes needles formed from a
high carbon steel material. The micropen 100 is inserted in the
adaptor 200 prior to needling operations, and inserted such that
the connection section 212 is covering the second dial 115, and the
lower body 213 is covering the first dial 113. Each of the
connection section 212 and the lower body 213 is independently
rotatable with respect to the adaptor body 210 such that rotation
of the connection section 212 allows rotation and control of the
second dial 115, and the first dial 113, respectively. Further, the
connection section 212 and the lower body 213 are preferably
transparent such that the user may see the measurements on the
first and second dials 113, 115 and corresponding measurement
indicators 114, 116 while controlling each dial.
[0138] The first dial 113 and second dial 115 may be used for a
variety of adjustment functions of the needles 216. Preferably the
needles 216 can be adjusted in penetration depth and density.
However, other adjustments may be available for a user such as
needling speed. In an example, the first dial 113 is used for
adjusting an indexing angle and thus the density of the needles 216
and the second dial 115 is used for adjusting the penetration depth
of the needles 216. Density may be adjustable such that
perforations per square area is different between one configuration
and another; for example, rotation of the second dial 115 controls
rotation of the needling head 214 and because needles are
distributed according to different densities on the needling head
214 this controls the density of needling. However, it should be
appreciated that other mechanisms for controlling the density of
the needles 216 may be implemented. Further, the adaptor 200 may be
available with different types of needling heads 214 such that
using a first adaptor would provide a different needling density
than using a second adaptor.
[0139] In an example, density control of the number of
perturbations or skin perforations per square area of the target
surface is available in a low density, medium density, and high
density configuration for ease and simplicity to a user. The
density of needling referred to herein is determined by the number
of needles 216 in contact with a subject's skin at a given time
during a needling operation and per square area of the subject's
skin. The density may range in value and in an example the density
ranges in value from the ratio of skin perforations surface area to
the total skin surface area being 1% to that ratio being 40%. This
ratio may also include at least 1%, at least 5%, at least 10%, at
least 15%, at least 20%, at least 25%, at least 30%, at least 35%,
at most 5%, at most 10%, at most 15%, at most 20%, at most 25%, at
most 30%, at most 35%, or at most 40%. Thus, the first dial 113 may
include indicia that correspond to a low, medium, and high density
configuration, or may include percent indicia indicating the
percent of skin perforation.
[0140] In an embodiment, the overall operation of the needles 216
are such that the needles automatically extend in a z-axis that is
parallel with the longitudinal axis of the micropen 100. The
needles 216 subsequently retract and then index through a
predetermined angle, angle .theta.. This process then continues to
repeat for a period of time until the desired needling density, as
set by the first dial 113, is achieved.
[0141] Referring to FIGS. 3-8, different views of the micropen 100
are provided. The micropen 100 may include a rechargeable battery
or other power unit in the upper section of the micropen body 110,
a motor and drive mechanism between the first dial 113 and the
second dial 115, and a printed circuit board or control circuit
above the first dial 113 and at the area of power interface 111. In
an example, a light pipe 117 is included on the bottom surface of
the micropen 100 as shown in FIG. 8. This allows a user or operator
to view the needling end of the device during a needling operation
as light is projected from the light pipe 117 through the adaptor
200. FIG. 7 illustrates a solid upper surface 118 of the micropen
100 that may have a curvature or contour for design and ease of
handling function.
[0142] Referring to FIGS. 9-16, different views of the micropen 100
with the adaptor 200 are provided. Specifically, referring to FIGS.
9A and 9B, the cross-sectional overlap of the adaptor 200 with the
micropen 100 is illustrated.
[0143] Still referring to FIGS. 9A and 9B, the tapered shape and
transparent plastic material of the head covering 215 allows a user
to view the needles 216 beneath the head covering 215 during the
needling operation. Referring to FIGS. 11-16, different views of
the combined micropen 100 with adaptor 200 are shown.
[0144] FIGS. 17-24 illustrate different views of the needling
adaptor 200 for use with the micropen needling device 100.
Referring to FIGS. 17-18, the connection section 212 is configured
to receive the micropen 100 to provide the combined device
described above. FIG. 23 illustrates an upper surface view
including the connection section 212 of the adaptor 200, and FIG.
24 illustrates a bottom surface view of the adaptor 200 including
the needles 216.
[0145] Referring to FIGS. 25-40, a charging station 300 is also
provided for charging and communication with the micropen 100. The
micropen 100 may be directly inserted into the charging station 300
to provide the combined structure illustrated in FIGS. 25-32. The
charging station 300 includes the charging station body 310, a
station bottom surface 311 for placing on a table or other surface,
and a station electrical connection 312, a lighting ring in the
charging station 300 such that the station 300 is illuminated when
the micropen 100 is inserted. Different levels of light
illumination may indicate different levels of charge for the
micropen 100. Further, lighting levels may indicate when charging
is complete, or different colors of light may be used.
[0146] As illustrated in FIGS. 25A and 25B, the flush design of the
micropen 100 when inserted into the charging station 300 provides
for an aesthetically pleasing configuration and ease of handling
the combined device by a user. The bottom surface 311 allows the
combined device to be placed on a surface upright or stowed away
when not in used.
[0147] Referring to FIGS. 33-40, different views of the charging
station 300 without the micropen 100 are illustrated. The charging
station 300 includes an indicator 314 for indicating power and
whether charging is activated. Also, referring to FIGS. 33 and 34,
an upper section 313 is configured to receive the micropen 100. It
should be appreciated that communication between the charging
contacts 112 and the station 300 allows for charging of the
micropen 100 but also for other functions such as data transfer.
Referring back to FIG. 2, the four charging contacts 112 may
include power, ground, data, and overcharge contacts.
[0148] FIG. 95 is a diagram illustrating a perspective view of
another example of a micropen needling device 700 (not visible),
also referred to as the main unit, enclosed within a needling
adaptor 800, also referred to as the sheath assembly, in an
assembled state. FIG. 96 is a diagram illustrating an exploded view
of the micropen needling device 700 enclosed within the needling
adaptor 800 in a disassembled state.
[0149] Referring to FIG. 95, the needling device 700 is fully
encapsulated within the needling adaptor 800 so that all parts of
the needling device 700 are protected from the outside environment.
This provides users or doctors with a device that is capable of
being maintained at the most sterile conditions. For example, the
needling device 700 may be used with a first needling adaptor 800
on a first subject, and then the first needling adaptor 800 may be
removed and replaced with a second needling adaptor for use on a
second subject while keeping the needling device 700 entirely
protected from the outside environment. The needling adaptor 800 is
provided in a sterile condition prior to being removed from
packaging; this provides an advantage in that the system does not
require a clinic, a doctor, or a user to sterilize the equipment.
In another example, the needling device 700 may be used with
different types of needling adaptors 800 having different types of
needling arrays on the same subject. That is, a patient may use a
needling adaptor 800 for hair growth applications, and subsequently
use a different needling adaptor 800 for tattoo or scar removal
without a need to sterilize the needling device 700 because it is
fully encapsulated and protected from the outside environment
during use. This provides at least prevention of
cross-contamination, among other benefits such as ease of use and
replacability, and reduced manufacturing costs.
[0150] Referring to FIG. 96, the needling device 700, which in some
embodiment is micropen needling device 700, includes a micropen
body 710, a micropen cap 720, and one or more buttons 730 for
control of the needling device 700. The one or more buttons 730 may
include buttons for controlling a penetration depth or a speed of
the needling operation or perturbations applied to a subject's
skin, an on/off power button for the needling device 700, a power
control of a light tube that allows light to exit from a distal end
of the needling device 700 to illuminate the perturbation region,
and a trigger button, that is separate from the power button, for
powering on the needling mechanism when pressed down by a user and
powering off the needling mechanism when released by a user. In an
example, needle penetration depth adjustment is controlled by a
user rotating an adaptor cap 820 which in turn rotates the micropen
cap 720 and a motor chassis 740 as described further below in
reference to FIG. 98.
[0151] Still referring to FIG. 96, the needling adaptor 800
includes an adaptor body 810, an adaptor cap 820 for controlling
and/or rotating the micropen cap 720, one or more buttons 830 for
controlling the one or more buttons 730 of the encapsulated
needling device 700, and a needle housing 840 surrounding a
plurality of needles 842. The needle housing 840 may receive a
transparent needle cover (not shown) having the same shape as the
needle housing for covering and protecting the needles. The adaptor
cap 820 and the one or more buttons 830 of the needling adaptor 800
cooperate with the micropen cap 720 and the one or more buttons 730
of the needling device 700, respectively. More specifically, in an
example, the adaptor cap 820 includes a projection that interacts
with a groove 722 of the micropen cap 720 (shown best in FIG. 97)
so that rotation of the adaptor cap 820 causes rotation of the
micropen cap 720. In addition, the one or more buttons 830 of the
needling adaptor 800 cover and directly interact with the one or
more buttons 730 of the needling device 700 so that a user may
press the one or more buttons 830 of the needling adaptor 800 to
control operations of the needling device 700 while it is
encapsulated. In another example, the needling device 700 can be
formed without buttons 730 and capable of connecting remotely to
the needling adaptor 800 via wireless connection so that the
buttons 830 of the needling adaptor 800 control the needling
operations without pressing down on internal buttons.
[0152] FIG. 97 is a diagram illustrating a cross-sectional view of
the needling device 700 enclosed within the needling adaptor
800.
[0153] Referring to FIG. 97, the needling device 700 further
includes a battery or powering mechanism 724 for powering the
device 700, a battery clip 725 for holding a position of the
battery 724, and a motor 726 for powering the needling operation as
described in further detail below in reference to FIGS. 99 and 100.
The internal components of the needling adaptor 800 of this example
include a bio-barrier 812 as an additional layer of protection and
sealing of the needling device 700, and a drive shaft interface 814
that is connected to the needles 842 and removably attachable to a
drive shaft 712 of the needling device 700. The interaction of the
drive shaft interface 814 with the drive shaft 712, such as by a
female-male attachment, allows for the needling device 700 to be
securely attached to the needling adaptor 800 after it is placed
within the needling device 700 and pushed fully within the needling
adaptor 800. A snap feel and/or sound provides users with the
assurance that the devices are secured together and ready for use.
This positive engagement provides for a needle array coupling means
the reduces vibration in the device and facilitates a higher
quality procedure
[0154] FIG. 98 is a diagram illustrating a perspective view of the
inner components of the needling device 700.
[0155] Referring to FIG. 98, the inner components of the needling
device 700 include the micropen cap 720, the battery 724, the
battery clip 725, and the motor 726, as described above. In
addition, the needling device 700 includes a motor shaft 718 that
extends from the motor 720, an angled hub 716 secured to the motor
shaft 718, a wobble plate 714 that is received by the angled hub
716, and the drive shaft 712 that is connected to the wobble plate
714. The inner components of the needling device 700, including at
least the motor 726, the motor shaft 718, the angled hub 716, the
wobble plate 714, and the drive shaft 712, are connected by a
chassis 740 that is configured to hold together all components and
move the components along the longitudinal axis of the needling
device 700. The chassis 740 may be attached to the micropen cap 720
by a chassis pin 742 so that rotation of the micropen cap 720 in
one direction moves the inner components axially in one direction
towards or away from the subject's skin, and rotation of the
micropen cap 720 in the opposite direction moves the inner
components in the opposite direction. This in turn controls the
penetration depth of the needles 842 prior to initiating the
perturbation stroke of the needles 842 using the motor 726 and the
corresponding actuation mechanisms 712, 714, 716, 718.
[0156] FIG. 99 is a diagram illustrating a magnified view of the
actuation mechanisms 712, 714, 716, 718 of the needling device 700,
and FIG. 100 is a diagram illustrating an exploded view of the
actuation mechanisms 712, 714, 716, 718 of the needling device
700.
[0157] As also described above and best illustrated in FIG. 100,
the motor shaft 718 extends from the motor 720, the angled shaft
716 is secured and is rotated by the motor shaft 718, the wobble
plate 714, which has a rotating element 714a fixed to the
angled-shaft 716 and a non-rotating element 714b connected to the
drive shaft 712. The rotating element 714a and non-rotating element
714b are joined by a bearing element. As the motor shaft 718
rotates, the angled shaft 716 is rotated by the motor shaft 718.
The non-rotating element 714b of the wobble plate oscillates in the
plane of the motor axis, toward and away from the subject's skin
surface, with each revolution of the motor shaft 718. The extent of
the oscillation defines the travel of the needle holder 844
available for the needling operation.
[0158] Referring now to FIG. 101, the attachment of the needles 842
to the drive shaft 712 is more clearly illustrated. The needles 842
are arranged in an array on a needle holder 844 that is secured to
the drive shaft interface 814. The drive shaft interface 814 is
removably attached to the drive shaft 712 so that the axial
displacement of the drive shaft 712, as described above, causes the
axial displacement of the drive shaft interface 814, the needle
holder 844, and the needles 842. In addition, the bio-barrier 812
may be securely attached about the needle holder 844 and configured
to move axially with the needle holder 844. Other components that
are illustrated include the previously described adaptor body 810,
bio-barrier 812, needle housing 840, micropen body 710, actuation
mechanisms 712, 714, 716, 718, and motor 726.
[0159] FIG. 102 is a diagram illustrating a cross-sectional view of
the needling adaptor 800 without the needling device 700. The
needling adaptor 800 includes the adaptor body 810, having a needle
housing 840, and the adaptor cap 820 that are securely attached to
one another, the one or more buttons 830, the drive shaft interface
814, the needle holder 844, and the needles 842. The needling
adaptor 800 is disposable and is intended for a single treatment
session. The needles 842 and needle holder 844 may have a variety
of different shapes and configurations. In this example, the needle
holder 844 is rectangular and the needles 842 are arranged in two
parallel rows.
[0160] FIGS. 103, 104, and 105 are diagrams illustrating different
views of the needles 842 and needle holder 844. As illustrated in
FIGS. 103-105, the needles 842 are arranged on the rectangular
needle holder 844 in two parallel or substantially parallel rows
that extend across the rectangular needle holder 844. Substantially
parallel as used herein means in the range of plus or minus 10% In
this example, there are 12 needles 842 with 6 needles 842 on a
first row 846 and 6 needles 842 on a second row 847. Also, the
needles 842 of the first row 846 are offset from the needles 842 of
the second row 847 so that a needle on a first row 846 is
horizontally between and equidistant from two needles on a second
row 847. In another example, three rows or more may be used. In an
example, the needles 842 are arranged in a rectangular arrangement
so that the distance covered by the needles 842 in one row is
greater than the distance covered by the needles 842 in one column.
In another example, the needle holder may have a circular shape as
illustrated in the example of FIGS. 18 and 24, and the needles 216
may be arranged on the circular shaped holder.
[0161] Advantages of the needles 842 and needle holder 844 being
arranged in a rectangular configuration include allowing a user or
physician the ability to view the target region during the needling
operation. In another example, the shape of the needle holder
allows the user to follow a more precise needling pattern of a
series of straight lines that do not overlap which also provides
for a quicker and more efficient needling operation in contrast to
a rounded arrangement of needles or a circular needle array.
5.1.2 Aspects of the Described Embodiments of the Needling
Device
[0162] In an aspect, the needling devices and needling adaptors
described in all embodiments above suitable to promote hair
follicle neogenesis through targeted cutaneous perturbation (TCP)
of the skin (e.g., the scalp). In a specific embodiment, TCP refers
to integumental perturbation of one or more epidermal layers (see,
e.g., Sections 5.3 and 5.4), for example, the basal and/or
suprabasal epidermal layers. In a specific embodiment, the
integumental perturbation performed by the needling devices and
needling adaptors described herein is followed by the application
of a compound (see, e.g., Section 5.6) to the skin. Without being
bound by any particular theory, TCP triggers generation of new hair
follicles by induction of epithelial stem cells. See, e.g.,
Sections 5.3 and 5.4 for a more detailed discussion of integumental
perturbation and methods of using the needling devices and needling
adaptors. In other examples, the needling devices and needling
adaptors or interchangeable needling adaptors with needle arrays
having different configurations (such as is illustrated in the
example of FIGS. 18 and 24) can be used for other applications such
as wrinkle reduction, scar revision, hair removal, and tattoo
removal.
[0163] In an example, the needling devices and needling adaptors of
all embodiments may form a combined rechargeable, battery powered,
handheld instrument. The devices are used to perform TCP by
reciprocating a needle array into and out of the scalp to "injure"
the scalp. The hand piece assemblies include a durable and reusable
needling device and a single-use needling adaptor that also acts as
a protective barrier such that the needling device is not exposed
to blood or other contaminated materials.
[0164] In an example, the needling devices of all embodiments may
include a sensor for detecting whether the needling adaptor is a
previously used needling adaptor so as to disallow reuse of the
previously used needling adaptor. The needling device and/or the
needling adaptor may also include a controller for determining when
the device is powered off and automatically retracting the needles
and/or adjusting the needle penetration depth to the most retracted
position in response to the device being powered off. The needling
device may also be used in combination with guides that fit over
the needle array in order to direct movement through a subject's
hair; for example, the guides can be similar to hair clipper
attachments. This limits the lateral movement of the needling
device and guides a user's hand in moving using straight line
strokes.
[0165] The adaptors of all embodiments, being a different component
of the combined device, provide complete insulation of the needling
device from the needles of the needling head. That is, because the
adaptor is a replaceable, removable, and disposable sheath, this
prevents blood contamination of the needling device and prevents
cross-contamination between different users of the needling device.
Equally important, these devices reduce the amount of time needed
to begin a needling operation because a doctor receives a sheath or
adaptor that is pre-sterilized once removed from its packaging and
the sheath protects the main needling device unit from any
contamination so it may be used immediately after with another
sheath or adaptor. This function allows for safe and easy use of
the devices.
[0166] In an example, the speed of needling may include three
discrete speeds (60 Hz, 100 Hz, 140 Hz), and may range from 60 Hz
to 140 Hz. The speed of needling includes at least 60 Hz, at least
70 Hz, at least 80 Hz, at least 90 Hz, at least 100 Hz, at least
110 Hz, at least 120 Hz, at least 130 Hz, at most 70 Hz, at most 80
Hz, at most 90 Hz, at most 100 Hz, at most 110 Hz, at most 120 Hz,
at most 130 Hz, and at most 140 Hz. In addition, needle penetration
depth adjustment may include incremental needle penetration depth
adjustment (0.5 mm above skin surface--2.5 mm below skin surface).
This prevents the dragging of the needle within the subject's skin
so that if the needles are in the 0.5 mm retracted position above
the skin, the needles are fully retracted and do not drag within
the subject's skin while the device is being moved by the user.
Reducing drag and having a light source lighting the target region
provides for higher quality procedure and more precise, more
consistent needling.
[0167] With regards to penetration depth control of the needles, a
variety of different penetration depth adjustments may be
available. In an embodiment, penetration depth may range from 0.5
millimeters in the retracted position to 2.5 millimeters; however,
it should be appreciated that the penetration depth of the needles
is available in a broader range. For example, the penetration depth
may include a range from -0.5 millimeters where the needles are in
a completely retracted position to a range of 5 millimeters or
more. The penetration depth may include at least -0.5 millimeters,
at least 0 millimeters, at least 0.5 millimeters, at least 1
millimeter, at least 1.5 millimeters, at least 2 millimeters, at
least 2.5 millimeters, at least 3 millimeters, at least 3.5
millimeters, at least 4 millimeters, at least 4.5 millimeters, at
most 0.5 millimeters, at most 1 millimeter, at most 1.5
millimeters, at most 2 millimeters, at most 2.5 millimeters, at
most 3 millimeters, at most 3.5 millimeters, at most 4 millimeters,
at most 4.5 millimeters, or at most 5 millimeters.
[0168] In one aspect, a needling device or needling adaptor
described herein is suitable for disrupting skin to a penetration
depth of between 30 .mu.m to 200 .mu.m (e.g., to a maximum depth of
30, 40, 50, 60, 70, 80, 85, 90, 95, 100, 105, 110, 120, 130, 140,
150, 160, 170, 180, 190 or 200 .mu.m), and preferably to
approximately 100-150 In one aspect, a needling device or needling
adaptor described herein is suitable for disrupting skin to a depth
of 100 In one aspect, a needling device or needling adaptor
described herein is suitable for disrupting skin to a depth of 150
.mu.m.
5.2 Applicator Devices
[0169] Examples of a needling device and other components including
adaptors and charging stations have been described, and a
description of fluid or drug applicators, massage heads for use
with drug applicators, cartridges for use with drug applicators,
and drug applicator charging stations will now be described in
reference to the remaining figures. The fluid or drug applicators
described herein may be used with any type of fluid. In an example,
the fluid applicator is a drug applicator that is used for the
application of minoxidil to a subject's scalp or for a variety of
different applications using different chemicals. With respect to
all embodiments of the drug or fluid applicators, it should be
appreciated that any type of fluid may be used and this invention
is not limited to the use of a drug. For convenience, the devices
may be referred to throughout the specification as "drug
applicators", "fluid applicators", or simply "applicators". Methods
of using the applicator devices described in this application are
provided in more detail in Section 5.4, below.
[0170] In one aspect, drug applicators may be used in combination
with other agents or treatments that stimulate hair growth. For
example, hair growth-promoting agents for use, alone or in
combination, in accordance with this aspect include but are not
limited to: agents affecting prostaglandins, such as Prostaglandin
F2.alpha. analogs, e.g. latanoprost (trade name Xalatan),
travoprost (trade name Travatan), tafluprost, unoprostone,
dinoprost (trade name Prostin F2 Alpha), AS604872, BOL303259X,
PF3187207, carboprost (trade name Hemabate); Prostamides, e.g.,
bimatoprost (trade names Latisse, Lumigan); Prostanoid receptor
agonists, e.g. fluprostenol; Prostaglandin D2 receptor antagonists,
e.g. laropiprant, AM211; Prostglandin E2 analogs, e.g. sulprostone;
and EP 2 receptor agonists, e.g. butaprost; 5.alpha.-reductase
inhibitors, such as, e.g., finasteride, dutasteride, turosteride,
bexlosteride, izonsteride, epristeride, epigallocatechin, Fluridil
(Sovak et al, Dermatol Surg. 2002; 28(8):678-685), RU 58841 (Pan et
al. Endocrine. 1998; 9(1):39-43),
N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17
beta-carboxamide (Rittmaster et al., J Clin Endocrinol Metab. 1987;
65(1):188-193), MK-386, azelaic acid, FCE 28260, SKF 105,111;
Minoxidil; ATP-sensitive potassium channel openers, e.g. diazoxide;
and the hair growth-promoting agents described herein or otherwise
known in the art, such as, e.g., kopexil (for example, the product
Keranique.TM.), CaCl.sub.2, botilinum toxin A, adenosine,
ketoconazole, DoxoRx, Docetaxel, FK506, GP11046, GP11511, LGD 1331,
ICX-TRC, MTS-01, NEOSH101, HYG-102440, HYG-410, HYG-420, HYG-430,
HYG-440, spironolactone, CB-03-01, RK-023, Abatacept,
Viviscal.RTM., MorrF, ASC-J9, NP-619, AS101, Metron-F-1, PSK 3841,
Targretin (e.g., 1% gel), MedinGel, PF3187207, BOL303259X,
AS604872, THG11331, PF-277343, PF-3004459, Raptiva, caffeine, and
coffee. Other hair-growth promoting agents include arginine,
isoleucine, leucine, lysine, methionine, phenylalanine, threonine,
tryptophan, valine, gamma linoleic acid and polyphenol catechins,
copper peptides. Other hair-growth promoting agents that can be
formulated as a hair wash tonic could include but are not limited
to, jojoba oil, extract of apple, saw palmetto, emu oil, beta
carotene and green tea. In another aspect, the applicators may also
be used in combination with drugs for alopecia being developed by
SWITCH Biotech LLC.
[0171] In addition, other compounds that may be used with the
applicator include compounds identified by the following company
and company ID, Actelion ACT-129968 (setipiprant), Actimis AP768,
Amira AM211, Amira AM461, Amgen AMG853, Array BiPharma ARRY-502,
AstraZeneca AZD1981, AstraZeneca AZD8075, AstraZeneca AZD5985,
Merck MK-7246, Novartis QAV680, Oxagen 00000459, Ocagen 00002417,
Pulmagen ADC3680B, Shionogi S-555739, BBI-5000, SM04554, and
KYTH105 (setipiprant).
[0172] In a specific embodiment, other compounds that may be used
with the applicator include agents described in Section 5.6, below.
In a specific embodiment, the compound(s) that may be used with the
applicator is in a dose as described in Section 5.7, below.
5.2.1 Illustrative Embodiments of the Applicator Device
[0173] Referring to FIGS. 41-48, different views of the applicator
400 with the massage head 500 attached thereto are provided. The
applicator 400 may be formed of one or more different materials
including but not limited to polycarbonate. The massage head 500
may be formed of one or more different materials including one or
more of synthetic rubber, silicone, and low durometer plastics. The
applicator 400 includes an applicator body 410 and an upper
covering surface 411. The details of the applicator components will
be described in further detail below in reference with FIGS. 89-93.
The massage head 500 includes a massage head body 510 and a number
of massage nubs 511, 512. The massage nubs 511, 512 include closed
nubs 512 and open nubs 511 that provide for the flow of a compound
directly to the subject's scalp. The opening in the open nubs 511
is directly at the bottom of each nub 511 thus allowing direct
access to the subject's scalp rather than the subject's hair.
[0174] FIGS. 49-56 illustrate different views of the applicator 400
as placed within the charging station 600. The charging station 600
includes a charging station body 610 and a charging station bottom
surface 612. The bottom surface 612 may be curved with a flat area
in the center to allow for the charging station 600 to stand
upright on a surface or table. The station 600 may come in a
variety of different colors and materials, but in an example, the
charging station 600 is transparent and capable of being
illuminated by light emitted from the applicator 400. As discussed
in more detail below in reference with FIG. 93, the applicator 400
may include an LED ring 430 that become more illuminated as the
applicator 400 becomes more charged. Accordingly, a user may detect
the amount of charge to the applicator 400 based on the illuminated
lighting of the transparent charging station 600.
[0175] FIGS. 57-64 illustrate different views of the charging
station 600 without the applicator 400. Referring to FIG. 57, the
charging station 600 includes an upper section 611 for receiving
and connecting to the applicator 400. The bottom surface 612 is
also illustrated in FIGS. 58 and 64. The charging station 600 is a
dock that fives the applicator 400 a base to charge up. The
charging station 600 can be plugged when needed for charging.
[0176] As illustrated in FIG. 93, an LED ring 430 of the applicator
400 may interact in various ways with the charging station 600. For
example, the light from the LED ring 430 may glow to indicate that
it is time for a subject or user to use the device. This may vary
based on the type or gender of the subject. Lifting the applicator
400 out of the charging station 600 will turn the lighting off and
acknowledge the subject's progress. Once placed back in the station
600, other alerts may indicate power or fluid level issues and will
also alert the subject or user of the next use period. Further,
while the applicator 400 is in the station 600, the applicator 400
may be rotated to adjust the intensity of chemical dispensing. The
LED ring 430 may change intensity to match the user's settings. The
applicator 400 may also be controlled by connecting with a smart
phone or device via Bluetooth LTE.
[0177] FIGS. 65-72 illustrate different views of a first massage
head 500 without the applicator 400. Referring to FIGS. 65 and 66,
the massage head 500 includes a massage head body 510, open nubs
511, closed nubs 512, massage head connecting surface 513, male
connecting projections 514, and a massage head central opening 515.
The connecting surface 513 is for receiving the applicator 400, and
the connecting projections 514 are for connection to corresponding
female connecting sections 452 of the applicator 400, as
illustrated in FIG. 90. The massage head 500, also known as a smart
head, is interchangeable and allows for treatment based on hair
type, regeneration goals, and comfort. The open nubs 511 include
dispensing tips, and in this example, there are three open nubs
511. The closed nubs 512 are for combing and massaging. The massage
head 500 may also include two sensor tips that are formed of
carbonized rubber material these inform when the tips are in
contact with the skin and can automatically initiate
activation.
[0178] FIGS. 73-80 illustrate different views of a second massage
head 500b without the applicator 400. Referring to FIGS. 73 and 74,
the massage head 500b includes a massage head body 510b, open nubs
511b, closed nubs 512b, a massage head connecting surface 513b, and
male connecting projections 514b. The connecting surface 513b is
for receiving the applicator 400, and the connecting projections
514b are for connection to corresponding female connecting sections
452 of the applicator 400, as illustrated in FIG. 90.
[0179] Referring to FIGS. 81-88, a third massage head 500c without
the applicator 400 is illustrated. Referring to FIGS. 81 and 82,
the massage head 500c includes a massage head body 510c, massaging
nubs 511c, a massage head connecting surface 513c, male connecting
projections 514c, and a massage head central opening 515c. The
connecting surface 513c is for receiving the applicator 400, and
the connecting projections 514c are for connection to corresponding
female connecting sections 452 of the applicator 400, as
illustrated in FIG. 90. This third massage head 500c aids a user in
finding areas of male pattern baldness.
[0180] Referring now to FIGS. 89-90, a description of the
components of the applicator 400 will be described. The applicator
400 may include a removable cartridge 450 in the central portion of
the applicator 400. This cartridge 450 may be used for Minoxidil
solution or other types of fluid.
[0181] The removable cartridge 450 may include female connecting
sections 452 for connecting with the male sections 514 of the
massage heads 500. Also, the cartridge 450 may include a
transparent upper surface window and walls for showing fluid
levels. Alternatively, fluid level can be communicated to the user
via LED display. The cartridge 450 also preferable includes nubs
that would correspond with nubs of the massage heads 500 and
include open tips for excreting the fluid directly through the
massage head open nubs 511.
[0182] Referring still to FIGS. 89 and 90, the drug applicator 400
includes an internal body 460 for housing the power and actuation
mechanisms 462, 464. Specifically, the internal body 460 may
include an actuation mechanism 462 such as a motor and actuator for
controlling the rotating aspects of the massage head 500. Also, the
internal body 460 may include a power mechanism 464 such as a
rechargeable battery for providing power to the applicator 400.
Further, the drug applicator 400 includes a dispensing mechanism
for ejecting the chemical through the drug applicator 400 and
massage head 500. A number of different dispensing mechanisms may
be used such as an actuatable piston as used in syringes, a vacuum
system for suctioning the fluid, or other pumping mechanism. While
the drug applicator 400 may include a power button for turning on
and off, in an example, the drug applicator 400 may turn on and off
by user contact or a touch interface on the device.
[0183] Referring now to FIG. 93, the applicator 400 may include a
tri-color LED array 430 and a light pipe 432. As discussed above in
the second and fourth paragraphs of Section 5.2.1, the LED array
430 may interact with the charging station 600 for providing
different functionalities and alerts to a user.
[0184] Referring to FIG. 94, other embodiments of the applicator
400 include a cartridge 450 that is removably attached to the top
of the applicator 400 instead of the applicator upper cover 411, or
a cartridge 450 that is combined with a massage head 500 to provide
a combined disposable cartridge and massage head structure.
[0185] FIG. 106 is a diagram illustrating a perspective view of
another example of a drug applicator 900 with a massage head 940
and a charging station 930.
[0186] Referring to FIG. 106, the drug applicator 900 includes an
applicator body 910, a keypad 905 including buttons for powering
and controlling the operations of the drug applicator 900, and a
charging station 930 which receives the drug applicator 900 for
charging. The buttons may include one or more of a power button for
powering the device on and off, a speed button for controlling the
speed of the massaging, and a mode button for setting a mode of the
operation such as setting to a massage only mode or to a massage
and dispense mode. In an example, the speed includes 3 discrete
speeds: 1 Hz, 2 Hz, 4 Hz. The charging station 930 may operate
using inductive charging as described in more detail in reference
to FIG. 107.
[0187] FIG. 107 is a diagram illustrating a cross-sectional view of
the drug applicator 900 with the massage head 940 and the charging
station 930. FIG. 108 is a diagram illustrating a cross-sectional
view of the drug applicator 900 with the massage head 940 and
without the charging station 930.
[0188] Referring to FIGS. 107 and 108 together, the drug applicator
900 further includes a controller 912, a position sensor 913, a
motor 914, a motor shaft 915, a battery or powering mechanism 916
for powering the drug applicator 900, a roller frame 911 for
holding the one or more rollers 911b (illustrated in FIG. 109), a
drive key 918 attached to the motor shaft 915, a cam drive 921 that
receives the drive key 918 and supports the rollers 911b, an
internal cavity 919 for receiving a cartridge 920 which contains a
liquid that is dispensable, a cartridge actuator 922 that is
configured to be actuated for dispensing the liquid from the
cartridge 920, and an LED ring 917 that is formed around an upper
circumferential portion of the applicator body 910 so that it is
visible 360 degrees about the applicator body 910 while the
applicator 900 is being charged in the charging station 930. In an
example, the LED ring 917 may indicate if the device is powered on
and may range in intensity of light in response to the level of
charge of the device; that is, the light may incrementally increase
as the device becomes more charged in the charging station 930.
[0189] Referring to FIG. 107 alone, the drug applicator 900 may be
charged by inductive charging; that is, using an electromagnetic
field to transfer energy from the charging station 930 to the drug
applicator 900 through electromagnetic induction. The charging
station 930 may include a charge coil 932 and the drug applicator
900 may include a corresponding coil 934 for interacting with the
charge coil 932 of the charging station 900 and charging the drug
applicator 900. In this example, the battery 916 is a rechargeable
battery and the use life per battery charge is 14 treatments, each
treatment cycle lasting approximately five minutes. Referring to
FIG. 108 alone, the cartridge 920 also includes a nozzle 927 for
dispensing the liquid and an orifice 923 extending through the
nozzle 927 and connected to the passageway through which the liquid
is dispensed from the cartridge 920. Also included with the drug
applicator 900 is a removable massage head 940 with one or more
massage nodules 941 for massaging a subject's skin.
[0190] The dispensing and massaging process will now be described
in reference to FIGS. 109-112 with a focus on the liquid dispensing
mechanism of the drug applicator 900 and the cartridge 920 placed
within the drug applicator 900. As previously described, the
cartridge 920 includes a reservoir for holding a liquid, for
example a drug, that is dispensed by the drug applicator 900. In
this example, the massaging and dispensing operations of the drug
applicator 900 are actuated by the same motor 914 and the motor
shaft 915 attached to the motor 914.
[0191] Referring to FIG. 109, a magnified perspective view of the
interaction between the roller frame 911 and the cam drive 921 is
illustrated. The cam drive 921 has an upper surface for receiving
rollers 911b of the roller frame 911. The upper surface includes a
flat or substantially flat, least-raised portion and gradually
rises to a most-raised portion. The rollers 911b and roller frame
911 remain fixed while the cartridge 920 is rotated by the motor
shaft 915. In another example, the drug applicator 900 operates
without a roller frame 911 or rollers 911b, and one or more bumps
or molded features are formed on the drug applicator 900 for
interaction with the cam drive 921. In fact, molded features might
obviate the need for rollers 911b, if friction between molded
features on the housing and the cam surfaces on the cartridge is
adequately low.
[0192] FIG. 112 is a diagram illustrating a perspective view of the
cam drive 921 for use with the drug applicator 900. Referring
briefly to FIG. 112, the cartridge 920 includes a receptacle 926
for receiving a drive key 918 at the end of the shaft 915. The
drive key 918 remains within the receptacle 926 throughout the
entire rotation of the cartridge 920 but may move up and down
within the receptacle 926 depending on the position of the
cartridge 920.
[0193] Referring back to FIG. 109, it should be appreciated that,
because the roller frame 911 and the rollers 911b are fixed, when
the rollers 911b are above the flat, least-raised portion, the
cartridge simply rotates. As the cartridge 920 is rotated further
by the motor shaft 915 so that the cam drive 921 is beneath the
rollers 911b at the gradually raised portion of the cam drive 921,
the top of the cartridge is pressed down and towards the cartridge
actuator 923 to begin dispensing. Once the rollers 911b reach the
most raised portion of the cam drive 921, the cartridge 920 is in
the most compressed position so that the dispensing cycle is fully
actuated. As the cartridge 920 is then rotated in the
counter-direction, the cartridge 920 is decompressed as the top of
the cartridge returns to its original position. The rotation angle
of the cartridge 920 may be sensed by the position sensor 913 which
may include three opto-electronic devices, either interrupter or
reflector, which sense moving flags or marks for determining the
stage of a cycle or the quantity of liquid or drug that is
dispensed, and send such data to the controller 912. The controller
912 communicates with the motor 914 for controlling the massaging
and dispensing operations.
[0194] FIG. 110 is a diagram illustrating a cross-sectional view of
the cartridge 920 for use with the drug applicator 900. In an
example, the cartridge 920 may be sold and packaged separately from
the drug applicator 900 and may be refillable with fluid or liquid.
In this example, the cartridge 920 may include a conventional,
off-the-shelf container with a piston 925 that may be placed within
the cartridge 920 when the cartridge 920 needs to be refilled. The
cartridge 920 includes an opening 924 extending through the
reservoir of the cartridge 920 through which liquid is suctioned to
the nozzle 927 and ultimately dispensed through the orifice 923 of
the nozzle 927. The cartridge actuator 922 interacts with the
cartridge 920 as explained in more detail in reference to the
suctioning operation and FIG. 111.
[0195] FIG. 111 is a diagram illustrating a perspective view of the
cartridge 920. As shown in FIG. 111, the cartridge actuator 922
includes one or more ribs 928 that are received in slots 929 formed
at the bottom portion of the cartridge 920 to ensure that actuator
922 and cartridge 920 rotate together and not relative to each
other. As described above, once the cartridge 920 is rotated so
that the rollers 911b are above the raised portion of the cam drive
921, the body of the cartridge 920 is pressed down and into the
cartridge actuator 921. Because the cartridge actuator 922
including the nozzle 927 is fixedly attached in the longitudinal
direction (up and down) to the massage head 940 which is fixedly
attached in the longitudinal direction (up and down) to the drug
applicator 920, the cartridge actuator 922 does not move up and
down within the drug applicator 900. Rather, the body of the
cartridge 920 is pressed so that the top of the cartridge 920 is
pushed down into the cartridge actuator 922. This pressing motion
dispenses drug. On counter-rotation, cartridge 920 returns to full
length and pump 924 refills with drug from the reservoir. Piston
925 slides to decrease reservoir volume. During operation, the
entire inner reservoir does not receive any air thus the cartridge
920 functions as an airless dispenser.
[0196] The massaging operation will now be described in reference
to FIGS. 113 and 114. FIG. 113 is a diagram illustrating a
cross-sectional view of the drug applicator 900 with the massage
head 940. FIG. 114 is a diagram illustrating a magnified view of
the attachment between the drug applicator 900, the cartridge 920,
and the massage head 940.
[0197] Referring to FIGS. 113 and 114, the cartridge 920 and
cartridge actuator 922 including the nozzle 927 and orifice 923 are
shown. The nozzle 927 is fixedly attached to the massage head 940.
As the cartridge 920 including the cartridge actuator 922 are
rotated, the massage head 940 is also rotated causing the massaging
operation. The massage head 940 is rotatably attached to a massage
head holder 942 by a bearing having one or more plates 943 that
slide on the surface of the massage head holder 942. The massage
head holder 942 including the attached massage head 940 and the
cartridge 920 are removably attached to the drug applicator 900 by
a collar including one or more securing elements 945. A user can
remove and replace the massage head 940 and attached portions for
swapping an empty cartridge 920 with a new, full cartridge 920. The
massage head 940 also includes cartridge securing nubs 940 for
receiving the bottom of the cartridge actuator 922. More
specifically, as best shown in FIG. 111, the cartridge actuator 922
includes a star-shaped bottom surface below the bars 928 and forms
gaps. Each of the gaps can have a cartridge securing nub 944 placed
within it so that the massage head 940 is secured to the cartridge
920 and both are rotated together. Accordingly, the rotating motion
is consistently applied to the whole cartridge 920 and the massage
head 940 while the massage head holder 942 does not rotate and is
fixedly attached to the drug applicator 900.
[0198] Referring to FIGS. 115 and 116, the massage head may be two
parts--a mechanical disc and a rubber portion--or, in another
example, the message head may be a single part with an elastomer
molded over a rigid disc. In these figures, a magnified
illustration of the massage head 940, massage nodules 941, the
massage head holder 942, the bearing plates 943, the cartridge
securing nubs 944, and the securing elements 945 is provided. It
should be appreciated that any of the shapes, types, designs, or
configurations of massage heads described above throughout this
application may be used with this drug applicator 900 and a number
of different types of massage heads 940 are interchangeable.
[0199] It should be appreciated that the keypad 905, the controller
912, and the position sensors 913 can work together for programming
the massaging and/or massaging and dispensing cycles of the drug
applicator 900.
5.2.2 Aspects of the Described Embodiments of the Applicator
Device
[0200] In all embodiments of the drug applicators described above,
the drug applicators may be programmed remotely using an external
or mobile device via Bluetooth.RTM. or other wireless
communications. In an example, the total dose is 1 ml per treatment
and is delivered in five pulses of 0.2 ml each (or an appropriate
number of smaller pulses). Each pulse is a full-stroke dispenser
actuation. In an example, the drug applicators may be programmed to
perform a Massage+Dispense cycle for 1 minute that is followed by a
Massage-only cycle for 5 minutes. A number of different
programmable cycles may also be selected by a user.
[0201] It should be appreciated that a number of different
compounds, liquids or drugs may be used with the drug applicators
and cartridges, and cartridges may be sold separately including a
variety of different compounds, liquids or drugs. In addition to
those described above in the second paragraph of Section 5.2, a
number of different drugs or compounds may be used including
proteasome inhibitor such as lactacystin, a peptidyl aldehyde, or
pentoxyfilline (PTX), and the compounds described in Section 5.6,
below.
[0202] For example, water cartridges may be used for practicing or
a cartridge including a healing solution may be used by those who
have had micro-needling procedures. Further, a special cleaning
cartridge can be provided for cleaning the applicator systems,
among other types of fluid and viscous material cartridges.
Cartridges may be 14 milliliters in volume to last for
approximately two weeks or more; however, other volumes should be
appreciated by those of skill in the art. For example, the volume
of the cartridge may range from 5 milliliters to 20 milliliters and
the volume includes at least 5 milliliters, at least 6 milliliters,
at least 7 milliliters, at least 8 milliliters, at least 9
milliliters, at least 10 milliliters at least 11 milliliters, at
least 12 milliliters, at least 13 milliliters, at least 14
milliliters, at least 15 milliliters, at least 16 milliliters, at
least 17 milliliters, at least 18 milliliters, at least 19
milliliters, at most 6 milliliters, at most 7 milliliters, at most
8 milliliters, at most 9 milliliters, at most 10 milliliters, at
most 11 milliliters, at most 12 milliliters, at most 13
milliliters, at most 14 milliliters, at most 15 milliliters, at
most 16 milliliters, at most 17 milliliters, at most 18
milliliters, at most 19 milliliters, and at most 20 milliliters.
Alternative design embodiments for the cartridges may include
smaller sized cartridges providing for daily or unit dosing such as
with metered dosing for syringes.
[0203] In an aspect, it should be appreciated that advantages of
the applicators include massaging and parting hair simultaneously
while dispensing a chemical, omni-directional movement of the
massage heads, a charging station acting as a light pipe and
luminous display, buttonless powering, remote control and smart
phone application control and monitoring, among other features. A
major concern with the use of minoxidil is that it is often mostly
applied to the hair rather than directly to the scalp. This is
ineffective and inefficient use of the compound as minoxidil must
reach the surface of the skin for optimal effect. The applicators
deliver drug directly to the skin and the massage mode spreads the
drug over the skin providing for more consistent and evenly
distributed administration of the drug. A problem with minoxidil
administration is that it is typically delivered to the hair and
not the scalp. Accordingly, among other advantages, the described
drug applicators provide a more effective means of applying the
compound to a subject's scalp.
[0204] In another aspect, it should be appreciated that the
cartridges described in all embodiments above may include a
two-chamber or multi-chamber cartridge for housing and dispensing
two or more drugs separately, or mixing two or more drugs and
dispensing the two or more drugs together. Further, all embodiments
of the applicators described above include an applicator that is
capable of detecting information related to an inserted cartridge
by detecting labeling provided on the inserted cartridge using RFID
technology. For example, the drug applicator is capable of
detecting any one or more of (a) whether a cartridge is provided by
the same manufacturer of the drug applicator device or a different
manufacturer, (b) what type of compound is in the cartridge, for
example, a Minoxidil-5% compound for men or Minoxidil-2% compound
for women, (c) how much compound is left in the cartridge, and (d)
the usage history of the cartridge, for example, whether this is
the first time that this cartridge has been inserted in a drug
applicator device or the number of times this cartridge was
previously inserted in a drug applicator device.
5.3 Integumental Perturbation
[0205] In a specific embodiment, a needling device and/or a
needling adaptor are suitable for performing integumental
perturbation on a subject. In a specific embodiment, a mobile app
described herein is suitable for measuring integumental
perturbation on a subject. In certain aspects, the needling device
and/or adaptor is used in a fashion that exerts control over the
extent of integumental perturbation (e.g., targeted cutaneous
perturbation (TCP)) and/or control over the way in which the
integumentally perturbed skin heals. In one embodiment,
integumental perturbation causes only superficial wounding to the
area of skin on which hair growth is desired. In a particular
embodiment, the extent of wounding is minimized by controlling the
depth of integumental perturbation. For example, integumental
perturbation can be controlled to limit perturbation to part or all
of the epidermis, to part or all of the stratum corneum, or deeper
into the papillary dermis, reticular dermis, and/or hypodermis. The
occurrence of pinpoint bleeding would indicate removal of the
stratum corneum, epidermis (or part thereof) and portions of the
upper layer of the dermis, such as the superficial papillary
dermis. The occurrence of increased bleeding would indicate deeper
penetration (and thus perturbation) into the deeper papillary
dermis and reticular dermis layer.
[0206] In one embodiment, integumental perturbation does not remove
the epidermis. In some embodiments, integumental perturbation
achieves removal of part of the epidermis. In some embodiments,
integumental perturbation removes the entire epidermis. In some
embodiments, integumental perturbation removes all of the epidermis
and part of the dermis. In some embodiments, integumental
perturbation removes part of the stratum corneum. In some
embodiments, integumental perturbation removes the stratum corneum.
In some embodiments, integumental perturbation removes part of the
papillary dermis. In some embodiments, integumental perturbation
removes part of the more superficial papillary dermis. In some
embodiments, integumental perturbation removes part of the deeper
papillary dermis. In some embodiments, integumental perturbation
removes the papillary dermis. In some embodiments, integumental
perturbation removes the reticular dermis, or part of the reticular
dermis. The depth of integumental perturbation depends on the
thickness of the skin at a particular treatment area. For example,
the skin of the eyelid is significantly thinner than that of the
scalp. The occurrence of pinpoint bleeding indicates that the
epidermis and portions of the dermis have been removed. Deeper
penetration can result in much more bleeding, and the perturbation
can go as deep as the hypodermis.
[0207] In particular embodiments, integumental perturbation is done
to a clinical endpoint of pinpoint bleeding. In some embodiments,
the depth reaches the level of blood vessels of the follicular
papilla. In some embodiments, the depth does not go deeper than the
level of blood vessels of the capillary loops in the dermal
papilla, e.g., the area of papillary dermis in between rete pegs.
In some embodiments, integumental perturbation does not penetrate
the dermis. In some embodiments, integumental perturbation does not
completely remove all, or in some embodiments, most, of the hair
follicles in an area of treated skin. In one embodiment,
integumental perturbation does not penetrate the reticular dermis.
In one embodiment, integumental perturbation does not penetrate
more than halfway through the papillary dermis.
[0208] In some embodiments, integumental perturbation penetrates
the skin to a depth of between 5 and 40 .mu.m, 40 and 100 .mu.m, 30
and 200 .mu.m, 50 and 150 .mu.m, 70 and 130 .mu.m, 80 and 120
.mu.m, 90 and 110 .mu.m, 95 and 105 .mu.m, or 100 and 150
.mu.m.
[0209] In some embodiments, integumental perturbation penetrates
the skin to a depth of at least 30 .mu.m. In some embodiments,
integumental perturbation penetrates the skin to a depth of 30
.mu.m. In some embodiments, the device penetrates the skin to a
depth of 50 .mu.m. In some embodiments, integumental perturbation
penetrates the skin to a depth of 60 .mu.m. In some embodiments,
the device penetrates the skin to a depth of 30-100 .mu.m. In some
embodiments, integumental perturbation penetrates the skin to a
depth of 60-100 .mu.m. In some embodiments, integumental
perturbation penetrates the skin to a depth of 60-200 .mu.m. In
some embodiments, integumental perturbation penetrates the skin to
a depth of 100 .mu.m. In some embodiments, integumental
perturbation penetrates the skin to a depth of 100-150 .mu.m. In
some embodiments, integumental perturbation penetrates the skin to
a depth of 150 .mu.m. In some embodiments, integumental
perturbation penetrates the skin to a depth of 100-200 .mu.m. In
some embodiments, integumental perturbation penetrates the skin to
a depth of 30-200 .mu.m. In some embodiments, integumental
perturbation penetrates the skin to a depth of 30, 35, 40, 45, 50,
55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125,
130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190,
195, or 200 .mu.m. In some embodiments, the maximum depth of
penetration is, e.g., 30, 40, 50, 60, 70, 80, 85, 90, 95, 100, 105,
110, 120, 130, 140, 150, 160, 170, 180, 190 or 200 .mu.m.
[0210] In some embodiments, integumental perturbation penetrates
the skin to a depth of 100-500 .mu.m. In some embodiments,
integumental perturbation penetrates the skin to a depth of less
than 500 .mu.m. In some embodiments, integumental perturbation
penetrates the skin to a depth of 500-1000 .mu.m. In some
embodiments, integumental perturbation penetrates the skin to a
depth of about 1 mm. In some embodiments, integumental perturbation
penetrates the skin to a depth of about 1 mm or more. In some
embodiments, integumental perturbation penetrates the skin to a
depth of about 2 mm. In some embodiments, integumental perturbation
penetrates the skin to a depth of about 2 mm or more. In some
embodiments, integumental perturbation penetrates the skin to a
depth of 1 mm to 3 mm. In some embodiments, integumental
perturbation penetrates the skin to a depth of 1 mm to 5 mm. In a
particular embodiment, integumental perturbation does not exceed
500 .mu.m. In a particular embodiment, integumental perturbation
does not exceed 1 mm. In a particular embodiment, the depth of
penetration of the skin by the device does not exceed 2 mm.
[0211] In a specific embodiment, integumental perturbation removes
the first 10-30 .mu.m of these dead skin cells.
[0212] In a specific embodiment, integumental perturbation removes
the stratum corneum and part or all of the epidermis by removing
the first 30-100 .mu.m of the skin. This is not deep enough to
remove the sebaceous gland, bulge, or hair papilla of existing
follicle structures. The removal of the epidermis can be detected
by the appearance of a shiny, smooth, whiteish layer of skin.
[0213] In a specific embodiment, integumental perturbation removes
the stratum corneum, all of the epidermis, and disrupts the
papillary dermis (e.g., between 100 .mu.m and 150 .mu.m of the
skin). Disruption of the papillary dermis can be detected by the
appearance of small pinpoints of blood in the treated area.
[0214] In a specific embodiment, integumental perturbation removes
the stratum corneum, the full epidermis, and part of the dermis
down to approximately 200 .mu.m.
[0215] In a specific embodiment, the integumental perturbation is
performed in a method of use described in Section 5.4.
5.4 Methods of Use
[0216] The devices described herein are suitable for achieving one,
two, or more biological outcomes described in Section 5.4.5(a).
Without being bound by theory, the devices described herein can
induce hair follicle neogenesis, and can also stimulate, activate,
and reorganize follicular structures in order to promote hair
growth. Many conventional pharmacologic treatments for hair growth
promotion (e.g., agents described in Section 5.6, below) encourage
the switch from vellus to terminal hair. In a specific embodiment,
the devices described herein are suitable for promoting the
formation of stimulated, activated and reorganized hair follicle
structures which correlate with increased vellus hair, if not
terminal hair. By increasing the number of stimulated and activated
hair follicles, and vellus hair or terminal hair, the devices
described herein may be suitable for providing additional
substrates for the action of these pharmacologic treatments. Thus,
in certain aspects, devices described herein are suitable for
increasing hair, increasing hair thickness, and/or yielding longer
lasting hair. Accordingly, such treatments may be more effective,
efficient, cost-effective, and user friendly as compared to the
pharmacologic treatment alone. For example, fewer treatments may be
required. The hair that results may be more cosmetically
satisfactory, longer lasting, thicker, more uniform, longer, and
properly pigmented hair. For example, in certain aspects, the
needling devices and/or needling adaptors described herein, when
used in combination with administration of a pharmacologic
treatment, are suitable for yielding a 1.25-fold, 1.5-fold, 2-fold,
2.5-fold, 3-fold, 3.5-fold, or 4-fold or more increase in one or
more of the biological outcomes described in Section 5.4.5(a) as
compared to treatment with the pharmacologic treatment alone. For
example, in a specific embodiment, a method of treatment described
herein comprising integumental perturbation (e.g., by a needling
device and/or adaptor described herein) and administration of a
pharmacologic treatment (e.g., an agent described in Section 5.6,
below) yields a 1.25-fold, 1.5-fold, 2-fold, 2.5-fold, 3-fold,
3.5-fold, or 4-fold or more increase in one or more of the
biological outcomes described in Section 5.4.5(a) as compared to
treatment with the pharmacologic treatment alone (i.e., without the
integumental perturbation step). In a specific embodiment, the
needling devices and/or needling adaptors described herein, when
used in combination with administration of a pharmacologic
treatment, are suitable for yielding one or more of the biological
outcomes described in Section 5.4.5(a) in at least 5%, 10%, 20%,
30%, 40%, 50%, 60%, 70%, 80%, 90%, or 98% of the time that a
control method requires to achieve the one or more biological
outcomes. In a specific embodiment, the needling devices and/or
needling adaptors described herein, when used in combination with
administration of a pharmacologic treatment, are suitable for
yielding one or more of the biological outcomes described in
Section 5.4.5(a) in at most 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%,
80%, 90%, or 98% of the time that a control method requires to
achieve the one or more biological outcomes. In a specific
embodiment, the control method is a method comprising
microdermabrasion and administration of an agent (e.g., an agent
described in Section 5.6, below). In a specific embodiment, the
control method is a method of treatment with the pharmacologic
treatment alone (i.e., without the integumental perturbation step).
The synergistic effect of the integumental perturbation and
administration of an agent described herein may be measured as an
improvement over a control subject (or a control skin site on the
same subject) receiving the agent and not the integumental
perturbation.
5.4.1 Methods of Using the Needling Device
[0217] In an example, methods of using a needling device include
providing a needling device, having a sheath assembly with a needle
array and a main unit including a motor for driving the needle
array, opening the sheath assembly and placing the main unit within
the sheath assembly so that the main unit is fully encapsulated and
protected from the outside environment; and powering on the
needling device. The method may further include removing the sheath
assembly and replacing the sheath assembly with another sheath
assembly having a different needle array.
[0218] For example, a needle array having a rectangular
configuration may be provided on a first sheath adaptor that is
used by a physician on a patient for hair growth applications.
After use, the first adaptor may be replaced by a second sheath
adaptor having a different needle array configuration, for example,
a circular needle array configuration. The needling device may be
used on different parts of one patient's skin without a need to
clean the needling device because it is fully encapsulated within
the adaptor sheath. Also, the needling device may be used on
different patients. For example, a physician may use the first
needling adaptor with the device on a first patient and then remove
and replace the first adaptor with a second needling adaptor for
use on a second patient. As described above in reference to the
description of the needling devices, a number of different
procedures may be conducted such as procedures for hair growth
applications, wrinkle reduction, scar revision, hair removal,
tattoo removal, and pigmentation.
[0219] In a specific embodiment, the needling device is used in a
method of treatment described in Section 5.4.5.
5.4.2 Methods of Using the Applicator Device
[0220] In an example, methods of using applicator devices include
providing an applicator comprising having a housing, a drug
delivery cartridge carried by the housing, and a massage head which
is mounted on the housing, powering on the applicator; and dispense
a drug automatically by a dispensing mechanism that is linked to
movement of the massage head or by any other dispensing mechanism.
In an example, the applicator devices are programmed by a physician
or any user to follow a preset cycle of massage-only or massage and
dispense; for example, a 5-minute massage cycle is followed by a
1-minute massage and dispense cycle. The device may be programmed
from a keypad on the device or wirelessly using an external
device.
[0221] The method may further include removing the massage head and
attached drug delivery cartridge; and replacing the massage head
and attached drug delivery cartridge with another massage head
having another drug delivery cartridge and other massage head
nodules having a different nodule arrangement. The method may
further include receiving notifications from and interacting with
the applicator using a remote user interface.
[0222] In a specific embodiment, the applicator device is used in a
method of treatment described in Section 5.4.5.
5.4.3 Methods of Using the Needling Device and Applicator Device
Together
[0223] A method of using needling devices and drug applicators
together for stimulating hair growth, may include providing a
needling device having a sheath assembly including a needle array;
and a main unit comprising a motor for driving the needle array;
providing a drug applicator for drug delivery and massaging,
including a housing; a drug delivery cartridge carried by the
housing; and a massage head which is mounted on the housing for
massaging a subject's skin; using the needling device to perform
targeted cutaneous perturbation for disrupting a layer of a human
scalp; and after using the needling device, using the drug
applicator for applying a drug to the disrupted layer of the human
scalp.
[0224] The method may further include disrupting the layer of the
human scalp that is the basal or suprabasal epidermal layer, with
the drug that is being applied being minoxidil or a proteasome
inhibitor including lactacystin, a peptidyl aldehyde, or
pentoxyfilline (PTX) or a compound described in Section 5.6.
[0225] In a specific embodiment, the needling device and applicator
device are used in a method of treatment described in Section
5.4.5.
5.4.4 Mobile App and Methods of Use in Combination with the
Needling Device and/or the Applicator Device
[0226] A mobile app may be used to control and provide feedback to
a physician or a user and may be used in combination with each of
the needling devices or fluid applicators. For example, a user may
control all aspects of the needling device and applicator device
including needle depth, needling speed, length of needling cycle,
applicator massaging speed, length of massaging cycle, amount of
fluid dispensed, speed of dispensing, and other aspects of a
needling, massaging, and dispensing operation as applicable to the
devices described in this application. The app may allow a user to
customize a needling, massaging, and dispensing procedure so that
the needler is controlled according to preset parameters, followed
by a cycle of massaging according to preset parameters, and
followed by a cycle of dispensing a fluid according to preset
parameters.
[0227] The mobile app may also be used to provide notifications to
a physician or a user. For example, the app may notify a user if a
procedure has not been performed for a period of time, whether it
is time for their next procedure, if a fluid cartridge needs to be
replaced, how much fluid is remaining in a fluid cartridge, the
current depth of needles in a needle array, the shape of the needle
array configuration, along with a number of other programmable
parameters of each of the needling devices and applicator
devices.
[0228] In a specific embodiment, the needling device, applicator
device, and/or mobile app are used in a method of treatment
described in Section 5.4.5.
5.4.5 Methods of Prophylactic and Therapeutic Use
[0229] The devices and/or mobile apps described herein are suitable
to achieve one or more biological outcomes described Section
5.4.5(a). Accordingly, provided herein is a method of treatment
comprising use of (i) a needling device and/or a needling adaptor
described herein; and/or (ii) an applicator device described
herein, on an area of skin of a subject in need thereof, wherein
the method of treatment achieves in the subject one or more
biological outcomes described in Section 5.4.5(a). In a specific
embodiment, the method further comprises use of a mobile app
described herein.
[0230] In a specific embodiment, provided herein is a method of
treatment, comprising (a) integumental perturbation of an area of
skin of a subject in need thereof, wherein the integumental
perturbation is performed by a needling device and/or adaptor
described herein; and (b) after a first period of time,
administering to the subject a first pharmaceutically effective
dose of an agent described in Section 5.6 or formulation thereof,
wherein the method of treatment achieves one or more biological
outcome described in Section 5.4.5(a). In a specific embodiment,
the method further comprises: (c) after a second period of time,
administering to the subject a second pharmaceutically effective
amount of the agent or formulation thereof. In a specific
embodiment, step (c) of the method is repeated 1, 2, 3, 4, 5, 6, 7,
8, 9, 10 or more times or until an outcome described in Section
5.4.5(a) is achieved. In a specific embodiment, the integumental
perturbation is as described in Section 5.3.
[0231] In a specific embodiment, provided herein is a method of
treatment, comprising administering a first pharmaceutically
effective dose of an agent described in Section 5.6 or formulation
thereof to an area of skin of a subject in need thereof, wherein
the area of skin is integumentally perturbed. In a specific
embodiment, the agent or formulation thereof is administered to the
subject after a first period of time, wherein the first period of
time is the time since the skin was integumentally perturbed. In a
specific embodiment, the method further comprises: (c) after a
second period of time, administering to the subject a second
pharmaceutically effective amount of the agent or formulation
thereof. In a specific embodiment, step (c) of the method is
repeated 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more times or until an
outcome described in Section 5.4.5(a) is achieved. In a specific
embodiment, the integumental perturbation is as described in
Section 5.3.
[0232] In a specific embodiment, a method of treatment provided
herein further comprises use of a mobile app described herein. In a
specific embodiment, the mobile app is suitable for determining one
or more of the biological outcomes described in Section
5.4.5(a).
[0233] In a specific embodiment, the area of skin is an area of a
subject in which hair growth is desired, for example, the scalp,
the face (e.g., the eyebrow, eyelashes, upper lip, lower lip, chin,
cheeks, beard area, or mustache area), or another part of the body,
such as, e.g., the chest, abdomen, arms, armpits (site of auxiliary
hair), legs, or genitals. In a specific embodiment, the area of
skin is the head. In a specific embodiment, the area of skin is the
scalp. In some embodiments, the area of skin is a balding scalp. In
a specific embodiment, the area of skin is not on the face. In a
specific embodiment, the area of skin is not on an area of the skin
that is normally covered with only, or mostly, vellus hair. In a
specific embodiment, hair restoration to a wounded or scarred part
of the skin is desired and/or scar revision is desired. Thus, in a
specific embodiment, the area of skin is a wounded or scarred part
of the skin. In a specific embodiment, the scar is caused by
surgery, such as a face lift, skin graft, or hair transplant.
[0234] In another embodiment, tattoo removal is desired. Thus, in a
specific embodiment, the area of skin is a tattooed area of the
skin.
[0235] In another embodiment, reduction in the visibility of a
wrinkle is desired. Thus, in a specific embodiment, the area of
skin is a wrinkled area of the skin.
[0236] In another embodiment, alteration in the pigmentation of
skin is desired. Thus, in a specific embodiment, the area of skin
is an area of the skin with altered pigmentation as compared to the
majority of the pigmentation of the skin of the subject.
[0237] In a specific embodiment, the area of skin is an area of
skin of any desired size, for example, between 0-3 mm in width
(e.g., 1 mm, 2 mm, 3 mm, or greater), 0-2 cm in width (e.g., 1 cm,
1.5 cm, and 2.0 cm), or greater (for example, up to 10%, 30%, 50%,
70%, 90%, or 100% of a subject's skin). Optionally, the area of
skin is interfollicular.
[0238] In a specific embodiment, the first period of time is less
than 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10
minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 45
minutes, 60 minutes, 3 hours, 6 hours, 12 hours, 24 hours, 2 days,
3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11
days, 12 days, 13 days, 14 days, 3 weeks, or 4 weeks. In a specific
embodiment, the first period of time between is at least 1 minute,
2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, 15 minutes,
20 minutes, 25 minutes, 30 minutes, 45 minutes, 60 minutes, 3
hours, 6 hours, 12 hours, 24 hours, 2 days, 3 days, 4 days, 5 days,
6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days,
14 days, 3 weeks, or 4 weeks. In a specific embodiment, the first
period of time between is at most 1 minute, 2 minutes, 3 minutes, 4
minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes,
30 minutes, 45 minutes, 60 minutes, 3 hours, 6 hours, 12 hours, 24
hours, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9
days, 10 days, 11 days, 12 days, 13 days, 14 days, 3 weeks, or 4
weeks.
[0239] In a specific embodiment, the agent is administered to the
subject via an applicator device described herein.
[0240] In a specific embodiment, the agent is administered to the
area of skin on the subject on which the needling device was
used.
[0241] In a specific embodiment, the second period of time is less
than 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10
minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 45
minutes, 60 minutes, 3 hours, 6 hours, 12 hours, 24 hours, 2 days,
3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11
days, 12 days, 13 days, 14 days, 3 weeks, or 4 weeks. In a specific
embodiment, the second period of time at least 1 minute, 2 minutes,
3 minutes, 4 minutes, 5 minutes, 10 minutes, 15 minutes, 20
minutes, 25 minutes, 30 minutes, 45 minutes, 60 minutes, 3 hours, 6
hours, 12 hours, 24 hours, 2 days, 3 days, 4 days, 5 days, 6 days,
7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14
days, 3 weeks, or 4 weeks. In a specific embodiment, the second
period of time is at most 1 minute, 2 minutes, 3 minutes, 4
minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes,
30 minutes, 45 minutes, 60 minutes, 3 hours, 6 hours, 12 hours, 24
hours, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9
days, 10 days, 11 days, 12 days, 13 days, 14 days, 3 weeks, or 4
weeks.
[0242] In a specific embodiment, the first pharmaceutically
effective dose of the agent is a dose described in Section 5.7. In
a specific embodiment, the second pharmaceutically effective dose
of the agent is a dose described in Section 5.7.
[0243] In some embodiments, the integumental perturbation induces a
wound in the skin. In a specific embodiment, the integumentally
perturbed skin is wounded. In some such embodiments, the wounded
skin is healed by primary intention. In other embodiments, the
wounded skin is healed by secondary intention. In yet other
embodiments, the wounded skin is healed by tertiary intention. In
certain embodiments, the wounded skin is healed more slowly than
usually indicated for that kind of wound. This may enhance scarless
wound healing and/or prolong the period during which hair growth in
the wounded area of skin is promoted. In a specific embodiment, the
method further comprises administering a post-perturbation wound
healing compound.
[0244] In a specific embodiment, the subject is a subject described
in Section 5.5.
[0245] In a specific embodiment, the method of treatment is a
method of treating a condition or disorder of a subject described
in Section 5.5.
[0246] For any of the treatments described above, in specific
embodiments, a particular treatment (e.g., integumental
perturbation) can be administered prior to, concurrently with, or
subsequent to the administration of a second (or third, or more)
treatment (e.g., administration of the first or second
pharmaceutically effective dose of the agent). In certain
embodiments, the second or third or later treatment comprises
treatment with the same active agent, albeit at a different (e.g.,
in one embodiment, higher) dose.
[0247] In one embodiment, one treatment is administered to a
subject at reasonably the same time as the other treatment. This
method provides that the two administrations are performed within a
time frame of less than one minute to about five minutes, or up to
about sixty minutes from each other, for example, at the same
doctor's visit. In another embodiment, one treatment and another
treatment are administered at exactly the same time.
[0248] In yet another embodiment, one treatment and the other
treatment are administered in a sequence and within a time interval
such that the one treatment and the other treatment can act
together to provide an increased benefit than if they were
administered alone. In another embodiment, the one treatment and
the other treatment are administered sufficiently close in time so
as to provide the desired outcome. Each can be administered
simultaneously or separately, in any appropriate form and by any
suitable route. In one embodiment, the one treatment and the other
treatment are administered by different routes of administration.
In an alternate embodiment, each is administered by the same route
of administration. In certain embodiments, the one treatment and
the other treatment can be administered at the same or different
sites of the subject's body. When administered simultaneously, the
one treatment and the other treatment may or may not be
administered in a single formulation, a mixture of formulations, or
at the same site of administration, or by the same route of
administration.
[0249] In various embodiments, the one treatment and the other
treatment are administered less than 1 hour apart, at about 1 hour
apart, 1 hour to 2 hours apart, 2 hours to 3 hours apart, 3 hours
to 4 hours apart, 4 hours to 5 hours apart, 5 hours to 6 hours
apart, 6 hours to 7 hours apart, 7 hours to 8 hours apart, 8 hours
to 9 hours apart, 9 hours to 10 hours apart, 10 hours to 11 hours
apart, 11 hours to 12 hours apart, no more than 24 hours apart or
no more than 48 hours apart. In other embodiments, the one
treatment and the other treatment are administered 2 to 4 days
apart, 4 to 6 days apart, 1 week a part, 1 to 2 weeks apart, 2 to 4
weeks apart, one month apart, 1 to 2 months apart, 2 to 3 months
apart, 3 to 4 months apart, 4 to 5 months apart, 6 months apart, 6
months to one year apart, or one year or more apart. In some
embodiments, the one treatment and the other treatment are
administered in a time frame where both are still active. One
skilled in the art would be able to determine such a time frame by
determining the half life of each administered component.
[0250] In one embodiment, the one treatment and the other treatment
are administered within the same patient visit. In one embodiment,
the one treatment is administered prior to the administration of
the other treatment. In an alternate embodiment, the one treatment
is administered subsequent to the administration of the other
treatment.
[0251] In certain embodiments, the one treatment and the other
treatment are cyclically administered to a subject. Cycling
treatment involves the administration of one or more treatments
once or for a period of time, followed by the administration of the
other treatment once or for a period of time, and repeating this
sequential administration. The first treatment may be with the one
treatment or with the other treatment, depending on the subject's
prior treatment history and the intended outcome. Not only does
such cycling treatment have the advantages described herein,
cycling treatment can also reduce the development of resistance to
one or more of the treatments, avoid or reduce the side effects of
one of the treatments, and/or improve the efficacy of the
treatment. In such embodiments, alternating administration of the
one or more treatments may be followed by the administration of
another treatment (or vice versa) 1 year later, 6 months later, 3
months later, 1 month later, 3 weeks later, 2 weeks later, 1 week
later, 4 to 6 days later, 2 to 4 days later, or 1 to 2 days later,
wherein such a cycle may be repeated as many times as desired. In
certain embodiments, the one (or more) treatments and the other
treatment are alternately administered in a cycle of 3 weeks or
less, once every two weeks, once every 10 days or once every week.
Such time frames can be extended or reduced depending on properties
of the treatment, e.g., whether a controlled release formulation is
used, and/or depending on the progress of the treatment course.
[0252] In a specific embodiment, an applicator device described
herein is suitable for administration of a compound to a subject.
Accordingly, provided herein is a method of administering a
compound to a subject in need thereof, comprising use of an
applicator device described herein. In a specific embodiment, the
compound is a compound described in Section 5.6.
[0253] (a) Biological Outcomes
[0254] In a specific embodiment, a needling device, a needling
adaptor, an applicator device, and/or a mobile app described herein
are suitable for achieving one or more of the biological outcomes
described herein. In a specific embodiment, a needling device
described herein is suitable for achieving one or more of the
biological outcomes described herein. In a specific embodiment, a
needling adaptor described herein is suitable for achieving one or
more of the biological outcomes described herein. In a specific
embodiment, an applicator device described herein is suitable for
achieving one or more of the biological outcomes described herein.
In a specific embodiment, a mobile app described herein is suitable
for achieving one or more of the biological outcomes described
herein. Accordingly, a method of treatment comprising use of one or
more of the devices described herein and/or the mobile app
described herein achieve one or more of the biological outcomes
described herein.
[0255] In a specific embodiment, the devices and/or mobile apps
described herein are suitable to achieve one or more of the
following nonlimiting examples of biological outcomes in a subject
on which the devices and/or mobile apps were used: hair growth
applications, wrinkle reduction, scar revision, hair removal,
tattoo removal, and pigmentation adjustment. Nonlimiting examples
of hair growth applications include increasing the amount of hair,
increasing hair thickness, increasing hair longevity, inducing hair
follicle neogenesis, treating baldness, treating alopecia,
promoting hair follicle development and/or activation on an area of
the skin of the subject, and/or treatment of a condition described
in Section 5.5.
[0256] In a specific embodiment, the devices and/or mobile apps
described herein are suitable to achieve one or more of the
following nonlimiting examples of biological outcomes in a subject
on which the devices and/or mobile apps were used: to promote
generation of new hair follicles ("follicle neogenesis"); to
promote formation of neogenic-like (NL) follicular structures; to
promote activation (possibly by reorganization) of existing hair
follicles; to promote formation of pre-existing-like (PEL) or
pre-existing-like, attached (PELA) follicular structures; to
promote development of hair follicles, for example, to promote the
growth of terminal hair (in preference to vellus hair); to promote
the branching of pre-existing hair follicles (seen as an increased
number of hair shafts per pore); to increase the width of hair
follicles (thereby promoting growth of an increased shaft width);
and/or to delay or prevent follicle senescence.
[0257] In a specific embodiment, the devices and/or mobile apps
described herein are suitable to achieve one or more of the
following nonlimiting examples of biological outcomes in a subject
on which the devices and/or mobile apps were used: to promote the
growth of hair; to promote growth of vellus hair; to promote the
transition of vellus hair to terminal hair; to increase the amount
of hair follicles in anagen, to prolong anagen, to shorten telogen,
to promote growth of terminal hair; to increase the amount of hair;
to increase the thickness of hair; and/or to reduce or prevent hair
loss.
[0258] In a specific embodiment, the devices and/or mobile apps
described herein are suitable to achieve one or more of the
following nonlimiting examples of biological outcomes in a subject
on which the devices and/or mobile apps were used: to promote the
growth of hair in follicular units; to promote growth of vellus
hair in follicular units, to promote the transition of vellus hair
in follicular units to terminal hair in follicular units; to
promote growth of terminal hair in follicular units; to increase
the amount of hair in follicular units; to increase the thickness
of hair in follicular units; and/or to reduce or prevent hair loss
or hair miniaturization in follicular units.
[0259] In one embodiment, the biological outcome is growth of hair
on the area of skin of a subject. In some embodiments, the
biological outcome is an increase in the amount or thickness of
hair on a treated area of skin of a subject. In some embodiments,
the biological outcome is an increase in the amount of vellus hair
on a treated area of skin of a subject. In some embodiments, the
biological outcome is an increase in the amount of terminal hair on
a treated area of skin of a subject. In some embodiments, the
biological outcome is the maintenance of terminal hair growth, i.e.
help prevent miniaturization of terminal hairs. In some
embodiments, the biological outcome is an increase in the ratio of
terminal-to-vellus hair on a treated area of skin of a subject. In
some embodiments, the biological outcome is an increase in the
amount of anagen hair or an increase in anagen growth on a treated
area of skin of a subject. In some embodiments, the biological
outcome is an increase in the ratio of anagen-to-telogen hair on a
treated area of skin of a subject. In some embodiments, the
biological outcome is hair follicle neogenesis in a treated area of
skin of a subject. In some embodiments, the biological outcome is
an increased number of hair follicles in a treated area of skin of
a subject. In some embodiments, the biological outcome is formation
of new hair follicles with nonvellus-sized hair shafts (i.e., hair
shafts with diameters equal to or greater than 30 microns) in a
treated area of skin of a subject. In some embodiments, the
biological outcome is an increased number of stimulated and
activated hair follicles, such as pre-existing hair follicles, in a
treated area of skin of a subject. In some embodiments, the
biological outcome is an increased number of pre-existing hair
follicles with nonvellus-sized hair shafts in a treated area of
skin of a subject In some embodiments, the biological outcome is
the presence and/or increased numbers of neogenic-like (NL)
follicular structures, pre-existing-like (PEL), and
pre-existing-like, attached (PELA) follicular structures.
[0260] Success of a device to achieve one or more of the biological
outcomes described herein and/or success of a method of the
invention can be measured by, for example: (i) improved overall
cosmetic outcome (e.g., using the Visual Analogue Scale (VAS));
(ii) patient assessment of his/her hair growth (e.g., based on
questionnaire); (iii) investigator assessment of hair growth in a
patient (e.g., based on a rating scale); (iv) patient assessment of
his/her hair growth in photographs; (v) investigator assessments of
hair growth in patient photographs; (vi) increased hair count
(e.g., by measuring new hair growth as an increased number of
fibers in an affected area of the skin); (vii) increased hair
density; (viii) increased thickness of hair or hair shaft (e.g.,
based on diameter); (ix) increased hair weight; (x) hair cuttings;
(xi) longer hair; (xii) increase in the amount of terminal hair
(by, e.g., measuring new hair growth as an increased number of
fibers in an affected area of the skin, or increased thickness
(e.g., diameter) or length of hair fibers); (xiii) increase in the
amount of vellus hair (by, e.g., measuring new hair growth as an
increased number of fibers in an affected area of the skin) (e.g.,
as measured photographically); (xiv) increase in the amount of
nonvellus hair, e.g., intermediate or terminal hair; (xv) an
increase in the ratio of terminal-to-vellus hair; (xvi) increased
number of hair germs; (xvii) increased number of hair follicles
(e.g., as evaluated by a skin biopsy); (xviii) increased number of
hair follicles at a more mature stage of development; (xix)
increased numbers of follicular units with 3 or more hair
follicles; (xx) increased hair follicle branching; (xxi) formation
of new hair follicles ("hair follicle neogenesis"); (xxii)
formation of new hair follicles with vellus-sized hair shafts
(i.e., hair shafts with diameters less than 30 microns); (xxiii)
formation of new hair follicles with nonvellus-sized hair shafts
(i.e., hair shafts with diameters 30 microns or greater); (xxiv)
hair follicle regeneration; (xxv) increased activation of existing
hair follicles; (xxvi) increased number of hair follicles; (xxvii)
increased number of activated hair follicles; (xxviii) increased
number of activated pre-existing hair follicles; (xxix) presence or
increased numbers of neogenic-like (NL) hair follicles (based on,
e.g., examination of a biopsy or by confocal microscope, by
assessing number of hair follicles, and/or by assessing morphology
of hair follicles compared to baseline or a negative control);
(xxx) presence or increased numbers of pre-existing hair follicles
(based on, e.g., examination of a biopsy or by confocal microscope,
by assessing number of hair follicles, and/or by assessing
morphology of hair follicles compared to baseline or a negative
control); (xxxi) presence or increased numbers of primitive
structures of interest (SOIs), such as neogenic-like (NL),
pre-existing-like (PEL), and/or pre-existing-like, attached (PELA)
follicular structures (based on, e.g., examination of a biopsy or
by confocal microscope, by assessing number of hair follicles,
and/or by assessing morphology of hair follicles compared to
baseline or a negative control, as described for example in Section
5.8.4 infra); (xxxii) increased number of pre-existing hair
follicles with vellus-sized hair shafts in a treated area of skin
of a subject; (xxxiii) increased number of neogenic-like hair
follicles with vellus-sized hair shafts in a treated area of skin
of a subject; (xxxiv) increase in the amount of anagen hair; (xxxv)
increase in the amount of telogen hair; (xxxvi) increased
proportion of hair follicles in anagen or decreased proportion of
hair follicles in telogen (i.e., an increase in the ratio of
anagen-to-telogen hair) (based on, e.g., examination of a biopsy or
phototrichogram); (xxxvii) increased proliferation of dermal
papilla (based on, e.g., examination of a biopsy); and/or (xxxviii)
increased recruitment or proliferation of stem cells to the
follicle (based on, e.g., examination of a biopsy).
[0261] In certain embodiments, the devices described herein are
suitable for achieving uniform integumental perturbations. For
example, in certain embodiments, the devices described herein are
suitable for achieving uniformity in the perforations of the
integumental perturbation. In a specific embodiment, uniformity is
measured by the variance in perforations per square centimeter. In
a specific embodiment, the uniformity is at least +/-1%, at least
+/-3%, at least +/-5%, at least +/-10%, at least +/-15%, at least
+/-20%, at least +/-30%, at least +/-50%. In a specific embodiment,
the uniformity is at most +/-1%, at most +/-3%, at most +/-5%, at
most +/-10%, at most +/-15%, at most +/-20%, at most +/-30%, at
most +/-50%, at most +/-60%, at most +/-70%, at most +/-80%, or at
most 90%.
[0262] In certain embodiments, success of treatment is assessed by
examination of hair follicles in a treated area of the subject's
skin. In certain embodiments, hair follicles are examined
histologically, or by determination of the presence or absence of
certain markers of hair follicle development or morphology. The
area of skin for examination may be obtained by biopsy, such as a
punch biopsy; alternatively or in addition, in a less invasive
method, the skin may be analyzed directly by, e.g., confocal
microscopy or other technique that permits imaging beneath the
surface of the skin.
5.5 Subject Populations that May be Treated Using the Needling
Device and/or the Applicator Device
[0263] The devices and/or mobile apps described herein are suitable
for use on subjects described herein. Thus, described herein are
candidate subjects for treatment with a device and/or one or more
methods described herein. In a specific embodiment, the subject is
any subject suffering from hair loss, hair thinning, balding, or
who has or has had a disease or condition associated therewith, or
who wishes to enhance the growth or thickness of hair or prevent
hair loss. In a specific embodiment, the subject has a tattoo and
wishes to remove or reduce the visibility of the tattoo. In a
specific embodiment, the subject has a wrinkle and wishes to remove
or reduce the visibility of the wrinkle. In a specific embodiment,
the subject has a scar and wishes to remove or reduce the
visibility of the scar. In a specific embodiment, the subject has
an altered pigmentation of an area of skin as compared to a control
area of skin on the subject, and wishes to remove or reduce the
visibility of the altered pigmentation.
[0264] The subject may be any subject, preferably a human subject,
including male, female, intermediate/ambiguous (e.g., XO), and
transsexual subjects. In certain embodiments, the subject is a
human adolescent. In certain embodiments, the subject is undergoing
puberty. In certain embodiments, the subject is a middle-aged
adult. In certain embodiments, the subject is a premenopausal
adult. In certain embodiments, the subject is undergoing menopause.
In certain embodiments, the subject is elderly. In certain
embodiments, the subject is a human of 1 year old or less, 2 years
old or less, 2 years old, 5 years old, 5 to 10 years old, 10 to 15
years old, e.g., 12 years old, 15 to 20 years old, 20 to 25 years
old, 25 to 30 years old, 30 years old or older, 30 to 35 years old,
35 years old or older, 35 to 40 years old, 40 years old or older,
40 to 45 years old, 45 to 50 years old, 50 years old or older, 50
to 55 years old, 55 to 60 years old, 60 years old or older, 60 to
65 years old, e.g., 65 years old, 65 to 70 years old, 70 to 75
years old, 75 to 80 years old, 80 to 85 years old, 85 to 90 years
old, 90 to 95 years old or 95 years old or older. In some
embodiments, the subject is a male 20 to 50 years old. In some
embodiments, the subject is a male 20 to 60 years old. In some
embodiments, the subject is a male 30 to 60 years old. In some
embodiments, the subject is a male 40 to 60 years old. In some
embodiments, the subject is a male or female 12 to 40 years old. In
some embodiments, the subject is not a female subject. In some
embodiments, the subject is not pregnant or expecting to become
pregnant. In some embodiments, the subject is not a pregnant female
in the first trimester of pregnancy. In some embodiments, the
subject is not breastfeeding.
[0265] The subject may have a disease or disorder of balding or
hair loss (including hair thinning), such as forms of nonscarring
(noncicatricial) alopecia, such as androgenetic alopecia (AGA),
including male-patterned hair loss (MPHL) or female-patterned hair
loss (FPHL) (e.g., thinning of the hair, i.e., diffuse hair loss in
the frontal/parietal scalp), or any other form of hair loss caused
by androgens, toxic alopecia, alopecia areata (including alopecia
universalis), scarring (cicatricial) alopecia, pathologic alopecia
(caused by, e.g., medication, trauma stress, autoimmune diseases,
malnutrition, or endocrine dysfunction), trichotillomania, a form
of hypotrichosis, such as congenital hypotrichosis, or lichen
planopilaris, or any other condition of hair loss or balding known
in the art or described infra.
[0266] In some embodiments, the subject has hair loss caused by a
genetic or hereditary disease or disorder, such as androgenetic
alopecia.
[0267] In some embodiments, the subject has hair loss caused by
anagen effluvium, such as what occurs during chemotherapy (with,
e.g., 5-fluorouracil, methotrexate, cyclophosphamide, vincristine).
In addition to chemotherapy drugs, anagen effluvium can be caused
by other toxins, radiation exposure (including radiation overdose),
endocrine diseases, trauma, pressure, and certain diseases, such as
alopecia areata (an autoimmune disease that attacks anagen
follicles.)
[0268] In some embodiments, the subject has hair loss caused by
telogen effluvium. Telogen effluvium is caused frequently by drugs
like lithium and other drugs like valproic acid and carbamazepine.
In addition to psychiatric drugs, telogen effluvium can be induced
by childbirth, traction, febrile illnesses, surgery, stress, or
poor nutrition. (See, Mercke et al., 2000, Ann. Clin. Psych.
12:35-42).
[0269] In some embodiments, the subject has hair loss caused by or
associated with medication, such as chemotherapy (e.g., anti-cancer
therapy or cytotoxic drugs), thallium compounds, vitamins (e.g.,
vitamin A), retinoids, anti-viral therapy, or psychological
therapy, radiation (such as the banding pattern of scalp hair loss
that may be caused by radiation overdose), trauma, endocrine
dysfunction, surgery, physical trauma, x-ray atrophy, burning or
other injury or wound, stress, aging, an autoimmune disease or
disorder, malnutrition, an infection (such as, e.g., a fungal,
viral, or bacterial infection, including chronic deep bacterial or
fungal infections), dermatitis, psoriasis, eczema, pregnancy,
allergy, a severe illness (e.g., scarlet fever), myxedema,
hypopituitarism, early syphilis, discoid lupus erythematosus,
cutaneous lupus erythematosus, lichen planus, deep factitial ulcer,
granuloma (e.g., sarcoidosis, syphilitic gummas, TB), inflamed
tinea capitis (kerion, favus), a slow-growing tumor of the scalp or
other skin tumor, or any other disease or disorder associated with
or that causes balding or hair loss known in the art or described
infra.
[0270] In some embodiments, the subject has hair thinning, or
"shock loss," or a bald patch caused by prior use as a source of
tissue or follicles for hair transplantation or follicular unit
transplantation.
[0271] In some embodiments, a candidate subject is a subject who
wishes to enhance hair growth, for example, to have more hair,
faster-growing hair, longer hair, and/or thicker hair. In some
embodiments, the candidate is a subject who wishes to increase hair
pigmentation. In some embodiments, the subject is not affected by a
condition of excessive hair loss.
[0272] As used herein, the terms "patient" and "subject" are used
interchangeably.
5.6 Agents
[0273] Also provided herein are agents that may be administered via
a device provided herein, used in combination with a device
described herein, and/or used in a method described herein. In a
specific embodiment, the agent is formulated in a pharmaceutical
composition. In a specific embodiment, the pharmaceutical
composition comprises the agent and a pharmaceutically acceptable
carrier or excipient. Pharmaceutically acceptable carriers and
excipients are known in the art.
[0274] In one aspect, the agent is an agent that promotes hair
growth. For example, hair growth-promoting agents for use, alone or
in combination, in accordance with this aspect include but are not
limited to: agents affecting prostaglandins, such as Prostaglandin
F2.alpha. analogs, e.g. latanoprost (trade name Xalatan),
travoprost (trade name Travatan), tafluprost, unoprostone,
dinoprost (trade name Prostin F2 Alpha), AS604872, BOL303259X,
PF3187207, carboprost (trade name Hemabate); Prostamides, e.g.,
bimatoprost (trade names Latisse, Lumigan); Prostanoid receptor
agonists, e.g. fluprostenol; Prostaglandin D2 receptor antagonists,
e.g. laropiprant, AM211; Prostglandin E2 analogs, e.g. sulprostone;
and EP 2 receptor agonists, e.g. butaprost; 5.alpha.-reductase
inhibitors, such as, e.g., finasteride, dutasteride, turosteride,
bexlosteride, izonsteride, epristeride, epigallocatechin, Fluridil
(Sovak et al, Dermatol Surg. 2002; 28(8):678-685), RU 58841 (Pan et
al. Endocrine. 1998; 9(1):39-43),
N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17
beta-carboxamide (Rittmaster et al., J Clin Endocrinol Metab. 1987;
65(1):188-193), MK-386, azelaic acid, FCE 28260, SKF 105,111;
Minoxidil; ATP-sensitive potassium channel openers, e.g. diazoxide;
and the hair growth-promoting agents described herein or otherwise
known in the art, such as, e.g., kopexil (for example, the product
Keranique.TM.), CaCl2, botilinum toxin A, adenosine, ketoconazole,
DoxoRx, Docetaxel, FK506, GP11046, GP11511, LGD 1331, ICX-TRC,
MTS-01, NEOSH101, HYG-102440, HYG-410, HYG-420, HYG-430, HYG-440,
spironolactone, CB-03-01, RK-023, Abatacept, Viviscal.RTM., MorrF,
ASC-J9, NP-619, AS101, Metron-F-1, PSK 3841, Targretin (e.g., 1%
gel), MedinGel, PF3187207, BOL303259X, AS604872, THG11331,
PF-277343, PF-3004459, Raptiva, caffeine, and coffee. Other
hair-growth promoting agents include arginine, isoleucine, leucine,
lysine, methionine, phenylalanine, threonine, tryptophan, valine,
gamma linoleic acid and polyphenol catechins, copper peptides.
Other hair-growth promoting agents that can be formulated as a hair
wash tonic could include but are not limited to, jojoba oil,
extract of apple, saw palmetto, emu oil, beta carotene and green
tea. In another aspect, the applicators may also be used in
combination with drugs for alopecia being developed by SWITCH
Biotech LLC. In addition, other agents include compounds identified
by the following company and company ID, Actelion ACT-129968
(setipiprant), Actimis AP768, Amira AM211, Amira AM461, Amgen
AMG853, Array BiPharma ARRY-502, AstraZeneca AZD1981, AstraZeneca
AZD8075, AstraZeneca AZD5985, Merck MK-7246, Novartis QAV680,
Oxagen OC000459, Ocagen OC002417, Pulmagen ADC3680B, Shionogi
S-555739, BBI-5000, SM04554, and KYTH105 (setipiprant). Further,
additional agents include proteasome inhibitors such as
lactacystin, a peptidyl aldehyde, or pentoxyfilline (PTX).
[0275] In one aspect, the agent is an agent that is useful in
reducing wrinkles. Agents useful in the reduction of wrinkles are
known in the art. Nonlimiting examples of agents useful in reducing
wrinkles include immune response modifier (IRM) compounds such as
idazoquinoline amine, a tetrahydroimidazoquinoline amine, an
imidazopyridine amine, a 1,2-bridged imidazoquinoline amine, a
6,7-fused cycloalkylimidazopyridine amine, an imidazonaphthyridine
amine, a tetrahydroimidazonaphthyridine amine, an oxazoloquinoline
amine, a thiazoloquinoline amine, an oxazolopyridine amine, a
thiazolopyridine amine, an oxazolonaphthyridine amine, a
thiazolonaphthyridine amine, or a combination thereof.
[0276] In one aspect, the agent is an agent that is useful in scar
revision. Agents useful in scar revision are known in the art.
Nonlimiting examples of agents useful in scar revision include
immune response modifier (IRM) compounds such as imidazoquinoline
amine, a tetrahydroimidazoquinoline amine, an imidazopyridine
amine, a 1,2-bridged imidazoquinoline amine, a 6,7-fused
cycloalkylimidazopyridine amine, an imidazonaphthyridine amine, a
tetrahydroimidazonaphthyridine amine, an oxazoloquinoline amine, a
thiazoloquinoline amine, an oxazolopyridine amine, a
thiazolopyridine amine, an oxazolonaphthyridine amine, a
thiazolonaphthyridine amine, or a combination thereof.
[0277] In one aspect, the agent is an agent that is useful in hair
removal. Agents useful in hair removal are known in the art.
Nonlimiting examples of agents useful in hair removal include
antiandrogens, androgen inhibitors, chromaphores, photosensitizers,
enzymes, phosphonic acid derivatives, matrix metalloproteinases,
and combinations thereof.
[0278] In one aspect, the agent is an agent that is useful in
tattoo removal. Agents useful in the tattoo removal are known in
the art. Nonlimiting examples of agents useful in tattoo removal
include immune response modifier (IRM) compounds such as compounds
with antiviral and/or anti-tumor activity, compounds that induce
the production and secretion of cytokines, purine derivatives,
imidazoquinoline amid derivatives, imidazopyridine derivatives,
benzimidazole derivatives, derivatives of a 4-aminopyrimidine fused
to a five membered nitrogen containing heterocyclic ring, certain
3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidine derivatives, and
aminoalkyl glucosaminide phosphates, 5% imiquimod
(1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amin) cream.
[0279] In one aspect, the agent is an agent that is useful in
pigmentation. Agents useful in pigmentation are known in the art.
Nonlimiting examples of agents useful in pigmentation include a
vitamin C derivative, niacinamide, cucumber extract, lemon extract,
and S-acyl glutathione derivatives.
[0280] In another aspect, the agent is a topical anesthetic.
[0281] As used herein, the terms "compound" and "agent" are used
interchangeably.
5.6.1 Hair Growth-Promoting Agents
[0282] In a specific embodiment, a compound described herein is a
hair growth-promoting agent.
[0283] The integumental perturbation methods described in Section
5.1 supra, alone or in combination with a post-perturbation
treatment described in Section 5.2 supra, may be used in
combination treatments with hair growth-promoting agents, and
optionally in combination with the treatments described in Section
5.4 below. In some embodiments, a hair growth-promoting agent
described herein promotes hair follicle development and growth,
resulting in the transition of vellus hair on an area of the skin
to non-vellus, e.g., intermediate or terminal, hair. In some
embodiments, a hair growth-promoting agent described herein acts
synergistically with the integumental perturbation method to
promote hair growth. The effect that each treatment offers could be
an additive or synergistic improvement, or a combination of two
different biologically defined effects, to achieve the desired end
result.
[0284] In some embodiments, the hair growth-promoting agent is a
treatment that promotes hair growth and/or treats a disease or
condition associated with excessive hair loss. Any treatment that
promotes hair growth and/or treats a disease or condition
associated with excessive hair loss that is known in the art or yet
to be developed is contemplated for use in accordance with these
embodiments.
[0285] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with one or more channel openers
(e.g., potassium channel opener, e.g., an ATP-sensitive potassium
channel (KATP opener), or an activator of such a channel), such as,
e.g., minoxidil (e.g., marketed as Rogaine or Regaine), diazoxide,
or phenytoin. In a particular embodiment, the hair growth-promoting
agent treatment comprises treatment with minoxidil. Commonly used
dosage forms of minoxidil that may be used in accordance with these
embodiments are topical solutions comprising 2% minoxidil or 5%
minoxidil, for example, topical minoxidil foam 5%.
[0286] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with one or more 5.alpha.-reductase
inhibitors. Non-limiting examples of 5.alpha.-reductase inhibitors
include finasteride, dutasteride (e.g., Avodart), turosteride,
bexlosteride, izonsteride, epristeride, epigallocatechin, MK-386,
azelaic acid, FCE 28260, and SKF 105,111. Commonly used dosage
forms of finasteride that may be used in such treatments are, for
example, oral finasteride at 1 mg/day. See, e.g., Physicians' Desk
Reference, 2009, 63rd ed., Montvale, N.J.: Physicians' Desk
Reference Inc., entries for Propecia.RTM. and Proscar.RTM. at pages
2095-2099 and 2102-2106, respectively, which are incorporated
herein by reference in their entireties.
[0287] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with one or more antiandrogens, such
as, e.g., finasteride (e.g., marketed as Propecia or Proscar),
ketoconazole, fluconazole, spironolactone, flutamide, diazoxide,
17-alpha-hydroxyprogesterone, 11-alpha-hydroxyprogesterone,
ketoconazole, RU58841, dutasteride (marketed as Avodart), fluridil,
or QLT-7704, an antiandrogen oligonucleotide, or others described
in Poulos & Mirmirani, 2005, Expert Opin. Investig. Drugs
14:177-184, the contents of which is incorporated herein by
reference.
[0288] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with one or more prostaglandin
F2.alpha. analogs, prostaglandin analogs, or prostaglandins.
Non-limiting examples of prostaglandin F2.alpha. analogs include
bimatoprost (e.g., Latisse, Lumigan), latanoprost (trade name
Xalatan), travoprost (trade name Travatan), tafluprost,
unoprostone, dinoprost (trade name Prostin F2 Alpha), AS604872,
BOL303259X, PF3187207, carboprost (trade name Hemabate). For
exemplary prostaglandin F2.alpha. analogs, as well as formulations,
dosages, and treatment regimens, for use in accordance with the
methods described herein, see, e.g., U.S. Pat. Nos. 8,017,655,
5,688,819, 6,403,649, 5,510,383, 5,631,287, 5,849,792, 5,889,052,
6,011,062, 7,163,959, 5,296,504, 5,422,368, 6,429,226, and
6,946,120, the entire contents of each of which is incorporated
herein by reference in its entirety. See also, with respect to
latanoprost, Uno et al., 2002, Acta Derm Venereol 82:7-12, the
contents of which is incorporated herein by reference in its
entirety.
[0289] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with one or more of the following
hair growth-promoting agents: kopexil (for example, the product
Keranique.TM.), CaCl2, botilinum toxin A, adenosine, ketoconazole,
DoxoRx, Docetaxel, FK506, GP11046, GP11511, LGD 1331, ICX-TRC,
MTS-01, NEOSH101, HYG-102440, HYG-410, HYG-420, HYG-430, HYG-440,
spironolactone, CB-03-01, RK-023, Abatacept, Viviscal.RTM., MorrF,
ASC-J9, NP-619, AS101, Metron-F-1, PSK 3841, Targretin (e.g., 1%
gel), MedinGel, PF3187207, BOL303259X, AS604872, THG11331,
PF-277343, PF-3004459, Raptiva, caffeine, an coffee. In some
embodiments, the hair growth-promoting agent treatment comprises
drugs for alopecia being developed by SWITCH Biotech LLC.
[0290] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with one or more of the following:
herbs (such as, e.g., saw palmetto, Glycine soja, Panax ginseng,
Castanea sativa, Arnica montana, Hedera helix geranium maculatum),
triamcinolone acetonide (e.g., suspension of 2.5 to 5 mg/ml for
injection), a topical irritant (e.g., anthralin) or sensitizer
(e.g., squaric acid dibutyl ester [SADBE] or diphenyl
cyclopropenone [DPCP]), clomipramine, unsaturated fatty acids
(e.g., gamma linolenic acid), a fatty acid derivative, thickeners
(such as, e.g., carbomer, glycol distearate, cetearyl alcohol), a
hair loss concealer, niacin, nicotinate esters and salts,
adenosine, and methionine. In some embodiments, the hair
growth-promoting agent treatment comprises treatment with nitroxide
spin labels (e.g., TEMPO and TEMPOL). See U.S. Pat. No. 5,714,482,
which is incorporated herein by reference.
[0291] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with an androgen receptor inhibitor,
which have been shown to be useful for stimulating scalp hair
growth (Hu L Y, et al., 2007, Bioorg Med Chem Lett. 2007
17:5983-5988).
[0292] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with a copper peptide(s), preferably
applied topically, or another compound with superoxide dismutation
activity. In some embodiments, the hair growth-promoting agent
treatment comprises treatment with an agent that increases nitric
oxide production (e.g., arginine, citrulline, nitroglycerin, amyl
nitrite, or sildenafil (Viagra)). In preferred embodiments, such
compounds are administered further in combination with a catalase
or catalase mimetic, or other antioxidant or free radical
scavenger.
[0293] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with a compound that mobilizes bone
marrow-derived stem cells (e.g., growth factors such as G-CSF
and/or chemical agents such as plerixafor (Mozobil.RTM.)); and/or
that regulates the differentiation of these stem cells into
gender-specific specialized human hair follicles (e.g., using
agents such as finasteride, fluconazole, spironolactone, flutamide,
diazoxide, 11-alpha-hydroxyprogesterone, ketoconazole, RU58841,
dutasteride, fluridil, or QLT-7704, an antiandrogen
oligonucleotide, cyoctol, topical progesterone, topical estrogen,
cyproterone acetate, ru58841, combination 5.alpha.-reductase
inhibitors, oral contraceptive pills, and others in Poulos &
Mirmirani, 2005, Expert Opin. Investig. Drugs 14:177-184,
incorporated herein by reference, or any other antiestrogen, an
estrogen, or estrogen-like drug (alone or in combination with
agents that increase stem cell plasticity; e.g., such as
valproate), etc., known in the art), that can result in, e.g., the
appearance of specialized follicles having features that are
different from natural follicles in the target location of
skin.
[0294] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with one or more agents that
counteract age-related hair thinning and/or hair follicle cell
senescence (also referred to herein as "anti-senescence agents")
for example, anti-oxidants such as glutathione, ascorbic acid,
tocopherol, uric acid, or polyphenol antioxidants); inhibitors of
reactive oxygen species (ROS) generation, such as superoxide
dismutase inhibitors; stimulators of ROS breakdown, such as
selenium; mTOR inhibitors, such as rapamycin; or sirtuins or
activators thereof, such as resveratrol, or other SIRT1, SIRT3
activators, or nicotinamide inhibitors.
[0295] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with one or more agents that induce
an immune response or cause inflammation, such as, e.g., tetanus
toxoid, topical non-specific irritants (anthralin), or sensitizers
(squaric acid dibutyl ester [SADBE] and diphenyl cyclopropenone
[DPCP]). While not intending to be bound by any theory, it is
thought that by contacting these agents to the skin, lymphocytes
and hair follicle stem cells may be recruited to skin. In some
embodiments, the hair growth-promoting agent treatment comprises
treatment with a chemical or mechanical (such as those discussed
infra) treatment that induces an inflammatory process in the skin.
While not intending to be bound by any theory, inducing
inflammation in the site where hair growth is desired helps to
recruit stem cells to the tissues that drive the formation of new
follicles.
[0296] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with an antiapoptotic compound. In
one embodiment, the antiapoptotic compound is not a Wnt or a Wnt
agonist.
[0297] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with stem cell therapy, hair cloning,
hair transplantation, scalp massage, a skin graft, hair plugs,
follicular unit extraction, or any surgical procedure aimed at hair
restoration.
[0298] In certain embodiments, a hair growth-promoting agent
described herein may be used at a dosage or in a range of dosages
known in the art for that agent (e.g., as made available on a
package insert or in the Physicians' Desk Reference). In other
embodiments the regular dosage of the hair growth-promoting agent
is adjusted to optimize a combination treatment (e.g., integumental
perturbation or treatment with another active ingredient) described
herein. For example, the regular dosage may be increased or
decreased as directed by the physician. For example, a lower dosage
may be used over a shorter duration owing to the synergistic effect
of combination with another treatment described herein.
[0299] In certain embodiments, the hair growth-promoting agent may
be used in its commercially available form. In other embodiments,
the form of the hair growth-promoting agent is adjusted to optimize
a combination treatment (e.g., integumental perturbation or
treatment with another active ingredient) described herein. In a
particular embodiment, the hair growth-promoting agent is
formulated as a different salt form than that which is commercially
available. In a particular embodiment, the hair growth-promoting
agent is formulated for topical administration, e.g., by
incorporation into a pharmaceutical composition for
post-perturbation treatment described in Section 5.2 infra.
[0300] In some embodiments, the hair growth-promoting agent
enhances conversion of vellus hair to non-vellus hair. In a
particular embodiment, the hair growth-promoting agent enhances
conversion of vellus hair to terminal hair. Exemplary hair
growth-promoting agents that promote conversion of vellus to
non-vellus hair that may be used in accordance with these
embodiments are prostaglandin F2.alpha. analogs (in one aspect,
latanoprost), minoxidil, etc. In some embodiments, the hair
growth-promoting agent enhances conversion of telogen hair to
anagen hair. In a particular embodiment, the hair growth-promoting
agent enhances conversion of telogen hair to anagen hair. Exemplary
hair growth-promoting agents that promote conversion of telogen to
anagen hair that may be used in accordance with these embodiments
are prostaglandin F2.alpha. analogs (in one aspect, latanoprost),
minoxidil, etc.
[0301] In some embodiments, the hair growth-promoting agent
treatment comprises treatment with an antiandrogen (e.g., a
5.alpha.-reductase inhibitor) and a channel opener (e.g.,
minoxidil). In one such embodiment, a 5.alpha.-reductase inhibitor
is administered in combination with minoxidil. In one such
embodiment, finasteride is administered in combination with
minoxidil. In some embodiments, the hair growth-promoting agent
treatment comprises treatment with a prostaglandin F2.alpha. or
prostamide analog (e.g., latanoprost, bimatoprost, etc.) in
combination with a channel opener (e.g., minoxidil). In one such
embodiment, a prostaglandin F2.alpha. or prostamide analog is
administered in combination with minoxidil. In one such embodiment,
latanoprost is administered in combination with minoxidil. In
another such embodiment, bimatoprost is administered in combination
with minoxidil.
[0302] In some embodiments, a treatment described herein for
promoting hair growth in a female subject does not comprise
finasteride or ketoconazole. In some embodiments, a treatment
described herein for promoting hair growth in a pregnant female
subject is not finasteride or ketoconazole.
[0303] In some embodiments a treatment described herein for
promoting hair growth does not comprise minoxidil. In some
embodiments a treatment described herein for promoting hair growth
does not comprise finasteride. In some embodiments a treatment
described herein for promoting hair growth does not comprise
dutasteride. In some embodiments a treatment described herein for
promoting hair growth does not comprise fluridil. In some
embodiments a treatment described herein for promoting hair growth
does not comprise spironolactone. In some embodiments a treatment
described herein for promoting hair growth does not comprise
cyproterone acetate. In some embodiments a treatment described
herein for promoting hair growth does not comprise bicalutamide. In
some embodiments a treatment described herein for promoting hair
growth does not comprise flutamide. In some embodiments a treatment
described herein for promoting hair growth does not comprise
nilutamide. In some embodiments a treatment described herein for
promoting hair growth does not comprise an inhibitor of an androgen
receptor. In some embodiments a treatment described herein for
promoting hair growth does not comprise an androgen antagonist. In
some embodiments a treatment described herein for promoting hair
growth does not comprise an anti-androgen.
5.7 Doses
[0304] The dose of the agent used in accordance with the devices
and/or methods provided herein should be adjusted so that maximum
benefit is achieved while reducing potential side effects.
[0305] In some embodiments, the target concentration of the agent
should be maintained in the skin or blood, and preferably the skin,
for at least 1 day; at least 2 days; at least 3 days; at least 4
days; at least 5 days; at least 6 days; at least 7 days; at least 8
days; at least 9 days; at least 10 days; at least 11 days; at least
12 days; at least 13 days; at least 14 days; at least 15 days; at
least 16 days; at least 19 days; or at least 21 days; and, in
certain embodiments, not more than 28 days. In certain embodiments,
the target concentration of the agent is maintained in skin or
blood, and preferably the skin, for 1 month or more, 2 months or
more, 3 months or more, 3 to 6 months or more, or 6 to 12 months or
more. This can be accomplished using, e.g., repeated applications
of the agent or a single application of a sustained release or
extended release agent formulation. For example, a modified release
form can be used to achieve the target concentration of the agent
for shorter maintenance periods (i.e., for at least 1, 2 or 3
days). Maintenance periods longer than 3 days may require repeated
application of the agent treatments. In some embodiments, it is
preferable to allow the concentration of the agent to decline
between dosages.
[0306] Care should be taken to avoid toxicity. In this regard, a
dosage should be chosen that maximizes efficacy while minimizing
toxicity. Patients should be monitored for toxic side effects
according to standard clinical practice. In some embodiments, agent
doses should be adjusted on the basis of the blood concentration
(serum or plasma) drawn (by convention) 12 or 24 hours after the
last dose of the agent. It may be possible to predict dosage
requirements for an individual patient based on the results of
administration of a single test dose, followed by a skin and/or
blood sample assay (plasma or serum) at the peak concentration
time; followed by blood sample assays to monitor toxicity at the 12
hour or 24 hour trough concentration; and 24 or 48 or 96 hours
later (when hair growth-promoting agent is generally eliminated)
which serves as the control value. Once the dose is established for
a patient, routine monitoring for toxicity is recommended. It may
also be possible to predict who will respond better to Minoxidil by
checking levels of minoxidil sulfotransferase (Buhl et al., J
Invest Dermatol. 1990; 95(5):553-557).
[0307] In another embodiment, the dose of the agent is a dose
sufficient to achieve one or more of the biological outcomes
described in Section 5.4.5(a).
5.8 Kits and Device Combinations
[0308] In an example, the devices described above may each be
packaged and sold separately, packaged separately and sold in
another packaging together, or packaged and sold together.
[0309] For example, a needling device may be sold in a package
including a needling device, an adaptor sheath with a rectangular
needing array, and a charging station. Also, the needling device
may be sold without the charging station. Also, the needling device
may be sold with a one or more additional needling adaptors or
sheaths having a different needling array such as a circular
needling array for providing a precision tip.
[0310] In another example, any embodiment of needling devices and
components as describe above may be sold with a fluid or drug
applicator. The drug applicator may include the applicator device,
one or more massage heads, one or more massage cartridges, and an
applicator charging station.
[0311] In a further example, the needling device and applicator are
sold together as a system with a needling device, a needling sheath
adaptor, a fluid applicator, a fluid cartridge, one or more
charging stations, and a software or a downloadable mobile app for
controlling each of the devices together and/or separately for
procedures involving needling, massaging, and fluid dispensing
cycles, separately or in combination.
[0312] It will be appreciated by those skilled in the art that
changes could be made to the embodiments described above without
departing from the broad inventive concept thereof. It is
understood, therefore, that the invention disclosed herein is not
limited to the particular embodiments disclosed, but it is intended
to cover modifications within the spirit and scope of the present
invention as defined by the appended claims.
* * * * *