U.S. patent application number 10/500861 was filed with the patent office on 2005-02-24 for ultrasonic percutaneous permeating device, ultrasonic percutaneous permeating kit, and ultrasonic percutaneous permeating method.
Invention is credited to Matsumura, Yuko, Sato, Yasuhiro.
Application Number | 20050043654 10/500861 |
Document ID | / |
Family ID | 27606031 |
Filed Date | 2005-02-24 |
United States Patent
Application |
20050043654 |
Kind Code |
A1 |
Matsumura, Yuko ; et
al. |
February 24, 2005 |
Ultrasonic percutaneous permeating device, ultrasonic percutaneous
permeating kit, and ultrasonic percutaneous permeating method
Abstract
Upon allowing a medicine 1 containing an active ingredient to
penetrate an organism 2 from a skin surface 2a, this ultrasonic
percutaneous penetration device A allows vibration of ultrasonic
waves to penetrate the organism from the skin surface. This device
is provided with an irradiation unit 4 that applies ultrasonic
waves having a frequency of not less than 0.5 MHz from skin 2a or a
surface capable of contacting the medicine, and a control unit 3
that controls irradiation conditions of the irradiation unit.
Inventors: |
Matsumura, Yuko;
(Takatsuki-shi, JP) ; Sato, Yasuhiro; (Kobe-shi,
JP) |
Correspondence
Address: |
GREENBLUM & BERNSTEIN, P.L.C.
1950 ROLAND CLARKE PLACE
RESTON
VA
20191
US
|
Family ID: |
27606031 |
Appl. No.: |
10/500861 |
Filed: |
October 20, 2004 |
PCT Filed: |
January 21, 2003 |
PCT NO: |
PCT/JP03/00455 |
Current U.S.
Class: |
601/2 ;
604/22 |
Current CPC
Class: |
A61B 17/54 20130101;
A61B 2017/00747 20130101; A61M 37/0092 20130101; A61M 35/003
20130101; A61M 2037/0007 20130101; A61B 2017/00765 20130101 |
Class at
Publication: |
601/002 ;
604/022 |
International
Class: |
A61H 001/00; A61H
001/02; A61H 005/00; A61B 017/20 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 21, 2002 |
JP |
2002-012143 |
Claims
1. An ultrasonic percutaneous penetration device, which, upon
allowing a medicine containing an active ingredient to penetrate an
organism from a skin surface, allows vibration of ultrasonic waves
to penetrate the organism from the skin surface, comprising: an
irradiation unit that applies ultrasonic waves having a frequency
of not less than 0.5 MHz from skin or a surface capable of
contacting the medicine; and a control unit that controls
irradiation conditions of the irradiation unit.
2. The ultrasonic percutaneous penetration device according to
claim 1, wherein the control unit controls at least one of factors
including the frequency, irradiation power, period between on and
off of power and irradiation time, which are irradiation conditions
of ultrasonic waves.
3. The ultrasonic percutaneous penetration device according to
claim 1, further comprising: a detection unit that detects the
depth of a portion for penetration of the medicine, wherein the
control unit controls the irradiation conditions so as to allow the
medicine to penetrate to the depth detected by the detection
unit.
4. The ultrasonic percutaneous penetration device according to
claim 1, wherein the irradiation unit applies not less than two
ultrasonic waves having different frequencies.
5. The ultrasonic percutaneous penetration device according to
claim 4, wherein the irradiation unit applies an ultrasonic wave
having a frequency of virtually 1 MHz and an ultrasonic wave having
a frequency of not less than 2 MHz.
6. The ultrasonic percutaneous penetration device according to
claim 1, further comprising: at least one tool selected from the
group consisting of a thermal tool for warming a portion to be
subjected to penetration of the medicine, a massaging tool for
repeatedly pressing and releasing the portion to be subjected to
penetration of the medicine, an electrostimulator that applies
electrical stimulation to the portion to be subjected to
penetration of the medicine and a photostimulator that applies
photic stimulation to the portion to be subjected to penetration of
the medicine.
7. An ultrasonic percutaneous penetration kit, which, upon allowing
a medicine containing an active ingredient to penetrate an organism
from a skin surface, allows vibration of ultrasonic waves to
penetrate the organism from the skin surface, comprising: a
medicine containing an active ingredient; an irradiation unit that
applies ultrasonic waves having a frequency of not less than 0.5
MHz from a surface capable of contacting the medicine; and a
control unit that controls irradiation conditions of the
irradiation unit.
8. The ultrasonic percutaneous penetration kit according to claim
7, wherein the control unit controls the frequency of the
ultrasonic waves to a frequency within a range from 3 to 7 MHz.
9. The ultrasonic percutaneous penetration kit according to claim
8, wherein the active ingredient is at least one active ingredient
selected from the group consisting of vitamin C, vitamin C
derivatives, kojic acid, glucoside, glutathione, kiwifruit extract,
rose fruit extract, arbutin and acerola extract.
10. The ultrasonic percutaneous penetration kit according to claim
7, wherein the active ingredient is at least one active ingredient
selected from the group consisting of vitamin A, vitamin A acid
derivatives, retinol, glutathione, .beta.-hydroxy acid and a cell
activation agent.
11. The ultrasonic percutaneous penetration kit according to claim
7, wherein: the active ingredient is at least one active ingredient
selected from the group consisting of vitamin B group, capsaicin
and caffeine, and the frequency of ultrasonic wave is controlled to
not less than 0.7 MHz by the control unit.
12. The ultrasonic percutaneous penetration kit according to claim
7, wherein the active ingredient is at least one active ingredient
selected from the group consisting of a thiocarbamate-based agent,
an imidazole-based agent, an allylamine-based agent, an
amorolfine-based agent, an undecylenic acid and derivatives
thereof, an antifungal agent and an antitrichophyton agent.
13. The ultrasonic percutaneous penetration kit according to claim
7, wherein the medicine is impregnated into a base material.
14. An ultrasonic percutaneous penetration method comprising the
step of: simultaneously as a medicine containing an active
ingredient is made in contact with the skin, applying ultrasonic
waves having a frequency of not less than 0.5 MHz to a skin surface
through the medicine.
15. An ultrasonic percutaneous penetration method comprising the
step of: after a medicine containing an active ingredient has been
made in contact with the skin, applying ultrasonic waves having a
frequency of not less than 0.5 MHz to a skin surface through a
medium that transmits ultrasonic waves.
16. An ultrasonic percutaneous penetration method comprising the
step of: after having applied ultrasonic waves having a frequency
of not less than 0.5 MHz to a skin surface, a medicine containing
an active ingredient is made in contact with the skin to which the
ultrasonic waves have penetrated.
17. An ultrasonic percutaneous penetration method comprising the
steps of: selecting two or more processes from the following three
processes: a process in which a medicine containing an active
ingredient is made in contact with the skin; a process in which
ultrasonic waves having a frequency of not less than 0.5 MHz are
applied to the skin surface; and a process in which, simultaneously
as the medicine containing an active ingredient is made in contact
with the skin, ultrasonic waves having a frequency of not less than
0.5 MHz are applied to the skin surface through the medicine, and
carrying out the selected processes time-serially in succession.
Description
TECHNICAL FIELD
[0001] The present invention relates to an ultrasonic percutaneous
penetration device which allows a medicine containing an active
ingredient to penetrate a portion of the organism percutaneously by
using ultrasonic vibration.
BACKGROUND ART
[0002] Conventionally, a DDS (drug delivery system, percutaneous
medicine delivery system) has been developed as a technique which
allows a medicine to penetrate percutaneously so that an active
ingredient of the medicine is applied to the skin and circulatory
system, and an iontophoresis method which allows penetration by
using electricity has developed considerably as a method of the
chemical administration. Moreover, techniques using ultrasonic
vibration have been gradually developed, and, for example, Japanese
Laid-Open Patent Publication No. 52-115591 has proposed a method in
which a medicine is allowed to penetrate a skin through irradiation
of ultrasonic waves having a frequency of 1 MHz for the treatment
of herpes, and Japanese Patent No. 2710281 has proposed a method in
which the ultrasonic wave output is properly controlled so as to
allow a medicine to penetrate a circulatory system.
DISCLOSURE OF INVENTION
[0003] In the above-mentioned method disclosed in Japanese
Laid-open Patent Publication No. 52-115591, in an attempt to
achieve the osmotic effect of a medicine for the skin lesion, the
medicine is allowed to penetrate by using an ultrasonic wave having
a frequency of 1 MHz with 1 W/cm.sup.2. However, when action of
ultrasonic waves to a target portion such as skin and fat and
characteristics of the ultrasonic waves are taken into
consideration, it cannot be said that the above-mentioned
irradiation conditions of ultrasonic wave are appropriate.
[0004] Moreover, in the method disclosed in Japanese Patent No.
2710281, the target portion for penetration of the medicine is the
circulatory system, and the ultrasonic waves are controlled so as
to allow the medicine to penetrate more effectively. However, the
objective of the invention described in this patent gazette is
limited to penetration of a medicine to only the circulatory
system, and no description has been given to the action thereof to
the skin that forms a via site.
[0005] Moreover, neither of the above-mentioned patent gazettes
describes anything about timing between the irradiation of
ultrasonic waves and the application of a medicine to the skin.
Here, when the fact that even after irradiation of ultrasonic
waves, the penetration effects of the ultrasonic waves continue,
which has been newly discovered by the inventors, etc. of the
present invention, is taken into consideration, the irradiation of
ultrasonic waves and the application of a medicine to the skin need
not be carried out simultaneously.
[0006] An objective of the present invention is to provide an
ultrasonic percutaneous penetration device which allows a medicine
to effectively penetrate the skin, fatty tissue and muscle tissue
safely.
[0007] Upon allowing the medicine containing an active ingredient
to penetrate the organism from the skin surface, the ultrasonic
percutaneous penetration device allows vibration of ultrasonic
waves to penetrate the organism from the skin surface, and is
provided with:
[0008] an irradiation unit that applies ultrasonic waves having a
frequency of not less than 0.5 MHz from skin or a surface capable
of contacting the medicine; and
[0009] a control unit that controls irradiation conditions of the
irradiation unit.
[0010] In accordance with the ultrasonic percutaneous penetration
device of the present invention, the ultrasonic waves having a
frequency of not less than 0.5 MHz are applied percutaneously. By
utilizing two characteristics, that is, a characteristic of
ultrasonic waves for loosening intercellular lipid of the skin
corneum and a characteristic of giving different actions to the
organism depending on different frequencies, it is possible to
allow a medicine to effectively penetrate a desired portion for
penetration. For this reason, it is possible to obtain effects of
improving the penetrating property several times higher than a
normal case in which the agent is simply applied to the skin.
Moreover, it is possible to prevent occurrence of skin disorder
such as bum on the skin surface, and consequently to allow a
medicine to effectively penetrate the organism safely.
[0011] Here, the control unit controls at least one of factors
including the frequency, irradiation power, period between on and
off of power and irradiation time, which are irradiation conditions
of ultrasonic waves.
[0012] Thus, it is possible to prepare optimal irradiation
conditions in response to a portion for penetration and a medicine
to be applied, and consequently to allow a medicine to effectively
penetrate the organism safely.
[0013] Moreover, a detection unit, which detects the depth of a
portion for penetration of the medicine, may be prepared, and in
this case, the control unit controls the irradiation conditions so
as to allow the medicine to penetrate to the depth detected by the
detection unit.
[0014] Thus, it becomes possible to allow the medicine to
positively penetrate a desired portion.
[0015] Here, the irradiation unit may apply two or more ultrasonic
waves having different frequencies. Moreover, the irradiation unit
may apply an ultrasonic wave having a frequency of virtually 1 MHz
and an ultrasonic wave having a frequency of not less than 2
MHz.
[0016] By applying two or more ultrasonic waves having different
frequencies to the skin, different actions are exerted on the
organism by the respective ultrasonic waves so that it becomes
possible to allow the medicine to more effectively penetrate a
desired portion for penetration.
[0017] Moreover, the above-mentioned device may further include any
one of the following tools: a thermal tool for warming a portion to
be subjected to penetration of the medicine, a massaging tool for
repeatedly pressing and releasing the portion to be subjected to
penetration of the medicine, an electrostimulator that applies
electrical stimulation to the portion to be subjected to
penetration of the medicine and a photostimulator that applies
photic stimulation to the portion to be subjected to penetration of
the medicine.
[0018] Upon allowing the medicine containing an active ingredient
to penetrate the organism from the skin surface, the ultrasonic
percutaneous penetration kit of the present invention allows
vibration of ultrasonic waves to penetrate the organism from the
skin surface, and is provided with:
[0019] a medicine containing an active ingredient;
[0020] an irradiation unit that applies ultrasonic waves having a
frequency of not less than 0.5 MHz from a surface capable of
contacting the medicine; and
[0021] a control unit that controls irradiation conditions of the
irradiation unit.
[0022] Here, the above-mentioned active ingredient may be a
whitening component, and in this case, the control unit controls
the frequency of the ultrasonic wave to a frequency in a range from
3 to 7 MHz.
[0023] By applying the ultrasonic wave to the skin under the
above-mentioned conditions, the medicine is allowed to safely
penetrate the base layer of the skin, and also to effectively react
with melamine existing in the base layer; thus, it becomes possible
to obtain high whitening effects.
[0024] Moreover, the whitening component may be at least one member
selected from the group consisting of vitamin C, vitamin C
derivatives, kojic acid, glucoside, glutathione, kiwifruit extract,
rose fruit extract, arbutin and acerola extract, and the
formulation may be at least one type selected from the group
consisting of gel type, lotion type, liquid type and impregnated
type.
[0025] With respect to the above-mentioned active ingredient, at
least one component for treating wrinkles, selected from the group
consisting of vitamin A, vitamin A acid derivatives, retinol,
glutathione, .alpha.-hydroxy acid and a cell activation agent, may
be used.
[0026] Moreover, with respect to the above-mentioned active agent,
at least one active ingredient used for burning fat, selected from
the group consisting of vitamin B group, capsaicin and caffeine,
may be used. In the above-mentioned case, the frequency of
ultrasonic wave is controlled to not less than 0.7 MHz by the
above-mentioned control unit.
[0027] By applying ultrasonic waves to the skin under the
above-mentioned conditions, it is possible to effectively burn fat,
and consequently to prepare appropriate slimming effects.
[0028] Furthermore, with respect to the above-mentioned active
ingredient, at least one active ingredient used for trichophytosis
treatment, selected from the group consisting of a
thiocarbamate-based agent, imidazole-based agents, an
allylamine-based agent, an amorolfine-based agent, undecylenic acid
and derivatives thereof, an antifungal agent and an
antitrichophyton agent, which are effective for Trichophyton
located in a deep portion of the corneum layer, may be used.
[0029] Here, the above-mentioned medicine may be impregnated into a
base material.
[0030] By impregnating the agent into the base material, the agent
is made to work on the skin surface stably for a long time; thus,
the penetrating effects of the medicine can be improved, and the
medicine such as a liquid can be easily handled.
[0031] In the ultrasonic percutaneous penetration method in
accordance with the present invention, simultaneously as the
medicine containing an active ingredient is made to contact the
skin, ultrasonic waves having a frequency of not less than 0.5 MHz
are applied to the skin surface through the above-mentioned
medicine.
[0032] In another method, after making the medicine containing an
active ingredient in contact with the skin, ultrasonic waves having
a frequency of not less than 0.5 MHz are applied to the skin
surface through a medium that transmits the ultrasonic waves.
[0033] As described above, the process in which the medicine is
made in contact with the skin is carried out prior to application
of the ultrasonic waves; therefore, the medicine is not susceptible
to limitations in the shape or the like required to transmit
ultrasonic waves to the skin. Therefore, the medicine to be
penetrated can be used as a packed product and the like.
[0034] In still another method, after having applied ultrasonic
waves having a frequency of not less than 0.5 MHz to the skin
surface, a medicine containing an active ingredient is made in
contact with the skin to which the ultrasonic waves have
penetrated.
[0035] Moreover, in still another method, two or more processes are
selected from the following three processes: a process in which a
medicine containing an active ingredient is made in contact with
the skin; a process in which ultrasonic waves having a frequency of
not less than 0.5 MHz are applied to the skin surface; and a
process in which, simultaneously as the medicine containing an
active ingredient is made in contact with the skin, ultrasonic
waves having a frequency of not less than 0.5 MHz are applied to
the skin surface through the medicine, and the selected processes
are carried out time-serially in succession.
BRIEF DESCRIPTION OF DRAWINGS
[0036] FIG. 1 is a schematic drawing that shows a structure of an
ultrasonic percutaneous penetration device in accordance with an
embodiment of the present invention.
[0037] FIGS. 2A to 2C are schematic drawings that show a
time-serial sequence of processes in one example of an ultrasonic
percutaneous penetration method in which the ultrasonic
percutaneous penetration device of the embodiment of the present
invention is used.
[0038] FIGS. 3A to 3C are schematic drawings that show a
time-serial sequence of processes in another example of an
ultrasonic percutaneous penetration method in which the ultrasonic
percutaneous penetration device of the embodiment of the present
invention is used;
[0039] FIG. 4 is a schematic drawing that shows a structure of
another example of an ultrasonic percutaneous penetration device in
accordance with the embodiment of the present invention;
[0040] FIG. 5 is a graph that shows comparisons in penetration
quantity of vitamin C in specific example 1 of the present
invention;
[0041] FIG. 6 is a graph that shows continuous penetration effects
of a medicine after irradiation with ultrasonic waves in specific
example 2 of the present invention; and
[0042] FIG. 7 is a graph that shows comparisons in changes in the
color of pigmentation in specific example 3 of the present
invention.
BEST MODE FOR CARRYING OUT THE INVENTION
[0043] The following description discusses embodiments of the
present invention.
[0044] FIG. 1 shows an example of an ultrasonic percutaneous
penetration device A of the present invention. This ultrasonic
percutaneous penetration device A is provided with a control unit 3
and an irradiation unit 4 placed inside a casing 10. This
irradiation unit 4 is provided with an ultrasonic vibrator that is
used for generating ultrasonic waves to be applied to a skin
surface 2a. Moreover, the control unit 3 has an electric circuit
that controls irradiation conditions of ultrasonic waves to be
applied from the ultrasonic transducer in the irradiation unit 4.
The control unit 3 controls at least one of irradiation conditions
of ultrasonic waves including frequency, irradiation power, period
between on and off of output (duty ratio) and irradiation time.
Here, the controlling operations of irradiation conditions by the
control unit 3 may be automatically carried out or may be manually
carried out. Further, the irradiation unit 4 of the ultrasonic
percutaneous penetration device A is placed close to the skin
surface 2a of an organism 2 so that ultrasonic waves are applied
from the ultrasonic transducer of the irradiation unit 4 to the
skin surface 2a, and then allowed to penetrate the organism 2 from
the skin surface 2a. In this case, the ultrasonic waves are
preferably applied to the skin surface 2a located on the surface
side of a target portion of the organism 2 that the ultrasonic
waves penetrate. The adjustments of the irradiation position, the
start of the irradiation and the like by the irradiation unit 4 may
be automatically carried out, or may be manually carried out.
[0045] By applying ultrasonic waves generated by the ultrasonic
percutaneous penetration device A of the present invention to the
skin surface 2a of the organism 2, vibration of the ultrasonic
waves is allowed to locally penetrate a target portion of the
organism 2 through the skin surface 2a. Thus, intercellular lipid
of the skin corneum is loosened by the vibration of the ultrasonic
waves (a state in which the fluidity between cells becomes higher),
the penetrating property of a medicine 1 and its active ingredient
to the target portion of the organism 2 is increased (the quantity
of penetration of the medicine 1 and its active ingredient is
increased). Moreover, ultrasonic waves are generated under
conditions suitable for allowing the medicine 1 to penetrate the
target portion of the organism 2, and applied to the skin surface
2a so that it becomes possible to further improve the penetrating
property of the medicine 1 and its active ingredient to the target
portion of the organism 2.
[0046] Here, the penetrating capability of ultrasonic waves to the
organism 2 differs depending on the frequency thereof, and when the
frequency is high, the energy is consumed at a shallow portion (in
the vicinity of the skin) of the organism 2, with the result that
the energy fails to penetrate the organism 2 into a deep portion.
In contrast, when the frequency is low, the consumption of the
energy at a shallow portion is small, with the result that the
energy is allowed to penetrate the organism 2 into a deep portion.
In accordance with the ultrasonic percutaneous penetration device A
of the present invention, by utilizing the above-mentioned
characteristics of ultrasonic waves, the medicine 1 is allowed to
locally penetrate a target portion of the organism 2
effectively.
[0047] Upon application of ultrasonic waves from the ultrasonic
percutaneous penetration device A of the present invention, the
irradiation conditions thereof can be altered on demand depending
on the target effects, and in an attempt to achieve whitening
effects, melamine located in the skin base layer that forms a
shallow portion of the organism 2 is given as a target to which the
active ingredient is applied; therefore, since the target is in a
shallow portion from the skin surface 2a, the medicine 1 is allowed
to effectively penetrate by using ultrasonic waves having a high
frequency (3 to 7 MHz). Moreover, in an attempt to reduce wrinkles,
the skin corium forms a target to which the active ingredient is
applied; therefore, the medicine 1 is allowed to effectively
penetrate by using ultrasonic waves having an intermediate
frequency (1 to 3 MHz). Furthermore, in an attempt to achieve
slimming effects, fat tissues and muscle layers, located at deeper
portions in the organism 2, form a target to which the active
ingredient is applied; therefore, the medicine 1 is allowed to
effectively penetrate by using ultrasonic waves having a low
frequency (0.5 to 2 MHz, preferably, 0.7 to 1 MHz) into a deep
portion thereof.
[0048] In this manner, the irradiation conditions of ultrasonic
waves, which are suitable for the depth of the target portion for
penetration of the medicine 1, need to be used in order to allow
the medicine 1 to effectively penetrate. Therefore, the ultrasonic
percutaneous penetration device A is capable of generating
ultrasonic waves having a frequency from 0.5 to 5 MHz, and the
frequency of the ultrasonic waves can be appropriately set within
this range.
[0049] The above description has discussed the frequency conditions
of ultrasonic waves to be used for effectively penetrating the
medicine 1, and conditions of the irradiation power of ultrasonic
waves also need to be taken into consideration. As described above,
in the case of high frequency of ultrasonic waves, since energy is
consumed in the shallow portion, the quantity of heat generation
becomes greater at the corresponding portion. Moreover, in the case
when the irradiation power of ultrasonic waves is great, since the
quantity of heat generation also becomes greater, there is the
possibility of generation of skin disorder such as bum. For this
reason, it is essential to use irradiation power in which the skin
disorder does not arise. In order to achieve high penetration
effects of the medicine 1 and its active ingredient without causing
the skin disorder, the irradiation condition of ultrasonic waves is
preferably set to not more than 2 W/cm.sup.2, more preferably, not
more than 0.7 W/cm.sup.2, with respect to the skin surface 2a,
within the above-mentioned frequency range. Thus, it becomes
possible to prevent the energy of ultrasonic waves from
concentrating on the skin, and consequently to allow the medicine 1
and its active ingredient to effectively penetrate safely. Here,
when the penetrating property of the agent 1 is taken into
consideration, the irradiation power is preferably set to not less
than 0.2 W/cm.sup.2 with respect to the skin surface 2a.
[0050] With respect to the medicine 1 to be percutaneously
penetrated by using the present invention, which contains an active
ingredient, at least one product, selected from the group
consisting of those compositions prepared as cosmetics (skin
lotion, milky lotion, essence, cream, gel-state cosmetics, etc.),
medical cosmetics, medicine articles and quasi-drugs as well as
those compositions that are water-soluble or oil-soluble with high
fluidity, and prepared on demand, may be used. Moreover, with
respect to the formation of the medicine 1 that corresponds the
type thereof, at least one type, selected from the group consisting
of gel type, lotion type, liquid type and impregnated type, may be
used.
[0051] The active ingredient to be contained in the medicine 1 can
be appropriately selected depending on the target effect. With
respect to the medicine 1 used for obtaining whitening effects, a
whitening agent is used, and this whitening agent contains at least
one active ingredient (whitening component) selected from the group
consisting of vitamin C, vitamin C derivatives, kojic acid,
glucoside, glutathione, kiwifruit extract, rose fruit extract,
arbutin and acerola extract. In an attempt to reduce wrinkles, the
medicine 1 preferably contains at least one active ingredient
selected from the group consisting of vitamin A, vitamin A acid
(retinoic acid) derivatives, retinol, glutathione, .alpha.-hydroxy
acid and a cell activation agent. Moreover, in an attempt to
provide a slimming effect, the medicine 1 preferably contains at
least one active ingredient used for burning fat, selected from the
group consisting of vitamin B group, capsaicin and caffeine.
Moreover, in an attempt to provide effects for trichophytosis
treatment, the medicine 1 preferably contains at least one active
ingredient selected from the group consisting of a
thiocarbamate-based agent, an imidazole-based agent, an
allylamine-based agent, an amorolfine-based agent, undecylenic acid
and derivatives thereof, an antifungal agent and an
antitrichophyton agent, which are effective for Trichophyton
located in a deep portion of the corneum layer.
[0052] Upon applying ultrasonic waves to the organism 2 while
allowing the medicine 1 to penetrate the target portion of the
organism 2 by using the ultrasonic percutaneous penetration device
A, the following three methods are proposed: A first method has an
arrangement in which the medicine 1 and ultrasonic waves are
simultaneously applied to the organism 2. As shown in FIG. 1, in
this method, the medicine 1 is applied onto the skin surface 2a
through a process such as coating, and with the medicine 1 being
left on the skin surface 2a, ultrasonic waves are applied to the
skin surface 2a of the organism 2. In this case, since the medicine
1 is allowed to penetrate from the skin surface 2a while ultrasonic
waves are being applied to the organism 2, the penetrating effect
of the medicine 1 becomes higher in comparison with the case in
which no ultrasonic waves are used.
[0053] A second method is a method in which after the application
of the medicine 1, ultrasonic waves are applied thereto. In this
method, as shown in FIG. 2A, after the application of the medicine
1 onto the skin surface 2a through a process such as coating, the
medicine 1 is left or removed therefrom to hardly remain on the
skin surface 2a as shown in FIG. 2B, and as shown in FIG. 2C,
ultrasonic waves are then applied to the skin surface 2a of the
organism 2. In this case, after a lapse of several minutes (about 5
to 10 minutes) from the time at which the medicine 1 has been
virtually eliminated from the skin surface 2a, ultrasonic waves are
applied thereto; however, the residual medicine 1 and active
ingredient on the skin surface 2a are allowed to percutaneously
penetrate so that the penetrating effect of the medicine 1 becomes
higher in comparison with the case in which no ultrasonic waves are
used.
[0054] A third method is a method in which ultrasonic waves are
applied prior to application of the medicine 1. In this method, as
shown in FIG. 3A, after ultrasonic waves have been applied onto the
skin surface 2a of the organism 2, the ultrasonic percutaneous
penetration device A and an ultrasonic wave transmission medium 25,
which will be described later, are removed, as shown in FIG. 3B,
and as shown in FIG. 3C, the medicine 1 is applied onto the skin
surface 2a through a coating process and the like. In this case,
the medicine 1 is used after the application of the ultrasonic
waves; however, since the loosened state of intercellular lipid of
the skin corneum due to the irradiation with ultrasonic waves
continues for at least 30 minutes, the medicine 1 is applied to the
skin surface 2a through a coating process or the like within 30
minutes since the application of ultrasonic waves so that the
medicine 1 and its active ingredient are allowed to percutaneously
penetrate so that the penetrating effect of the medicine 1 becomes
higher in comparison with the case in which no ultrasonic waves are
used.
[0055] With respect to the above-mentioned three methods, two or
more methods may be combined together to be carried out
time-serially in succession, or two or more methods may be
successively repeated.
[0056] Upon application of ultrasonic waves to the skin surface 2a
by using the ultrasonic percutaneous penetration device A, the
outer surface of the irradiation unit 4 or the outer surface of the
casing 10 may be directly made in contact with the skin surface 2a,
or, as shown in FIGS. 2 and 3, the ultrasonic wave transmission
medium 25 may be interpolated between the irradiation unit 4 and
the skin surface 2a. The ultrasonic wave transmission medium 25,
which is used for transmitting ultrasonic waves generated by the
irradiation unit 4 to the skin surface 2a, may be made from a
gel-state aqueous solution in which, for example, carboxy methyl
cellulose (CMC) is blended. The ultrasonic wave transmission medium
25, which is made closely in contact with both of the irradiation
unit 4 and the skin surface 2a upon application of ultrasonic
waves, is applied onto the skin surface 2a or impregnated into a
base material, which will be described later, so that the resulting
base material is bonded to the skin surface 2a; thus, this is
interpolated between the irradiation unit 4 and the skin surface
2a. Moreover, the ultrasonic wave transmission medium 25 may
contain the above-mentioned active ingredient to be prepared as the
medicine 1. Furthermore, the ultrasonic wave transmission medium
25, which contains the above-mentioned medicine 1, may be used.
[0057] Moreover, in the case when the medicine 1 is used for the
organism 2, in addition to applying the medicine 1 to the skin
surface 2a, the medicine 1 may be impregnated into a base material
to be maintained therein so that the resulting base material is
bonded to the skin surface 2a. With respect to the base material, a
cloth such as nonwoven fabric and a sheet-shaped material such as
paper, which are easily available, may be used. With this
arrangement in which the base material impregnated with the
medicine 1 to be maintained therein is bonded to the skin surface
2a, it is possible to maintain the state in which the medicine 1 is
made closely in contact with the skin surface 2a for a long time,
and consequently to improve the penetration effects of the medicine
1; moreover, it becomes possible to prevent the medicine 1 from
dripping down, and consequently to achieve easiness in
handling.
[0058] FIG. 4 shows another embodiment. This ultrasonic
percutaneous penetration device A is provided with a detection unit
5 which detects the depth of a portion that is subjected to
penetration of the medicine 1. The detection unit 5 utilizes the
characteristic of ultrasonic waves for use in diagnosis. While
applying ultrasonic waves to the organism 2, this detection unit 5
receives the ultrasonic waves reflected from the organism 2 so that
the depth of a portion to be subjected to the penetration of the
medicine 1 is measured and detected. The results of detection by
the detection unit 5 are sent to the control unit 3 in which
irradiation conditions of ultrasonic waves that are suitable for
the depth detected by the detection unit 5 are determined. Then,
based upon the irradiation conditions determined by the control
unit 3, the irradiation of ultrasonic waves from the ultrasonic
transducer in the irradiation unit 4 is controlled.
[0059] Moreover, two ultrasonic transducers 20 and 21 are installed
in the irradiation unit 4 of the ultrasonic percutaneous
penetration device A. These ultrasonic transducers 20 and 21 are
different in their types, that is, different in frequencies in
ultrasonic waves to be generated or different in their periods
between on and off outputs. Here, these ultrasonic vibrators 20 and
21 may be respectively used individually or may be used
alternately, depending on purposes, portions to be used or
irradiation conditions. The other structures and the methods of use
are the same as those described in the above-mentioned embodiments.
Additionally, not limited to two, three or more ultrasonic
vibrators may be installed. With this arrangement, ultrasonic waves
can be simultaneously applied to two or more portions of the
organism 2, or two or more kinds of ultrasonic waves having
different conditions may be applied alternately.
[0060] In the present embodiment, based upon the detection by the
detection unit 5, the depth of a portion to be subjected to
penetration of the medicine 1 is accurately confirmed, and the
irradiation conditions of ultrasonic waves suitable for the depth
can be selected so that it becomes possible to allow the medicine 1
effectively penetrate the target portion.
[0061] Moreover, the ultrasonic percutaneous penetration device A
of the present invention may be provided with a control unit 3 and
an irradiation unit 4 that can generate two or more ultrasonic
waves having different frequencies (frequency bands). For example,
in the case when two ultrasonic waves having different frequencies
are generated, the ultrasonic percutaneous penetration device A
shown in FIG. 4 allows the control unit 3 to carry out controlling
operations so that the frequency of an ultrasonic wave to be
generated from the ultrasonic transducer 20 and applied to the skin
surface 2a is made different from the frequency of an ultrasonic
wave to be generated from the ultrasonic transducer 21 and applied
to the skin surface 2a. In the case when these two ultrasonic waves
having mutually different frequencies are generated, with respect
to the ultrasonic wave to be applied to a deeper portion of the
skin, an ultrasonic wave having a frequency of approximately 1 MHz
(0.5 to 2 MHz) that is a frequency of a comparatively low band is
generated by one of the ultrasonic transducers 20 while, with
respect to the ultrasonic wave used for allowing the medicine 1 to
penetrate the organism 2, an ultrasonic wave having a frequency of
approximately 2 MHz or more that is a frequency of a comparatively
high band is generated by the other ultrasonic vibrator 20; thus,
the ultrasonic waves having these two frequencies may be combined
with each other, and simultaneously applied to the skin surface 2a.
Moreover, the above-mentioned ultrasonic percutaneous penetration
device can be switched so as to apply two or more ultrasonic waves
having different frequencies, and can also apply two or more
ultrasonic waves having different frequencies alternately or in
succession. Here, the ultrasonic wave having a frequency of a
comparatively high band, used for allowing the medicine 1 to
penetrate the organism 2, may be set to not more than 10 MHz.
[0062] Thus, two or more ultrasonic waves having different
frequencies are generated, and by simultaneously applying these two
ultrasonic waves to the skin surface 2a in combination, two or more
different functions, exerted by two or more ultrasonic waves having
different frequencies, are combined together, and applied to the
organism 2 (in combination); thus, it becomes possible to improve
the penetrating property of the medicine 1 to the organism 2.
[0063] Moreover, the present invention may be provided with at
least one or more physical stimulatory functions selected from the
group consisting of a physical stimulatory function for improving
the penetrating effect of the medicine 1 to the organism 2, a
physical stimulatory function for raising the comfortable feeling
for the user and a physical stimulatory function for adding another
action. For example, the physical stimulatory function for
improving the penetrating effect of the medicine 1 to the organism
2 includes a function for applying a warming stimulation to the
target portion of the organism 2 that is subjected to penetration
of the medicine 1, and an ultrasonic percutaneous penetration
device A is arranged so as to include a heat-generating tool
(warming tool) that applies a warming stimulation to the target
portion of the organism 2 by utilizing warm water, warm wind,
steam, infrared radiation, far infrared radiation, high frequency
and the like in its casing 10 and irradiation unit 4. The physical
stimulatory function for raising the comfortable feeling for the
user, for example, includes a function for applying massaging
stimulation to the target portion of the organism 2 that is
subjected to penetration of the medicine 1, and an ultrasonic
percutaneous penetration device A is arranged so as to include a
massaging tool that applies a massaging stimulation, such as
massaging, pounding, rubbing and repeated actions of pressing and
releasing, to the target portion of the organism 2, in its casing
10 and irradiation unit 4. Moreover, the physical stimulatory
function for adding another action, for example, includes a
function for applying a cell-activating stimulation to the target
portion of the organism 2 that is subjected to penetration of the
medicine 1, and an ultrasonic percutaneous penetration device A is
arranged so as to include a cell-activating tool that applies a
cell-activating stimulation to the target portion of the organism 2
by utilizing electric stimulation, photic stimulation laser and the
like, in its casing 10 and irradiation unit 4.
[0064] Next, the following description discusses the penetration
method of the medicine 1 of the present invention more
specifically.
SPECIFIC EXAMPLE 1
[0065] An ultrasonic percutaneous penetration device A, as shown in
FIG. 1, was used. With respect to a medicine 1, a whitening agent
was used. With respect to the whitening agent, 1 cc (1 cm.sup.3) of
gel-state aqueous solution to which carboxy methylcellulose (CMC)
containing 3% of vitamin C derivatives (magnesium ascorbyl
phosphate) was added was used. Here, the gel-state aqueous solution
to which carboxy methylcellulose (CMC) containing no vitamin C
derivatives was added corresponds to an ultrasonic wave
transmission medium 25.
[0066] The above-mentioned whitening agent was applied to a skin
surface 2a, and ultrasonic waves were then applied to this skin
surface 2a of an organism 2 from the irradiation unit 4 of the
ultrasonic percutaneous device A through the whitening agent so
that the medicine 1 was allowed to penetrate the skin (epidermis
basal lamina). At this time, the irradiation conditions of the
ultrasonic waves were set as follows: frequency: 5 MHz, irradiation
power to the skin surface 2a: 0.35 W/cm.sup.2, probe area of the
irradiation unit 4 (area in which the irradiation unit 4 is made in
contact with the skin surface 2a through the whitening agent): 4.52
cm.sup.2, an output method for ultrasonic waves (power): continuous
output (duty ratio: 100%), and irradiation time: 5 minutes.
[0067] With respect to the above-mentioned specific example 1, the
quantity of penetration of vitamin C (quantity of ascorbic acids
per 1 g of skin) was measured. Moreover, for comparative purposes,
with respect to those samples that had not been irradiated with
ultrasonic waves (control 1) in the above-mentioned specific
example 1, the quantity of penetration of vitamin C was also
measured. FIG. 5 shows the results thereof.
[0068] As clearly shown by FIG. 5, specific example 1 had about 5
times as much as vitamin C penetration in comparison with control
1, thereby indicating that the application of ultrasonic waves
provided high penetration effects for the medicine 1 and its active
ingredient in comparison with control 1.
SPECIFIC EXAMPLE 2
[0069] First, as shown in FIG. 2, the ultrasonic wave transmission
medium 25 was applied to a skin surface 2a in the same manner as
described above, and ultrasonic waves were applied to the skin
surface 2a by using the same ultrasonic percutaneous penetration
device A as specific example 1 through the ultrasonic wave
transmission medium 25, and allowed to penetrate the skin surface
2a. The same irradiation conditions as those of specific example 1
were used. Next, after the irradiation with ultrasonic waves, the
ultrasonic wave transmission medium 25 was removed from the skin
surface 2a, and this was allowed to stand still for 30 minutes.
Thereafter, the same whitening agent as that of specific example 1
was applied to the skin surface 2a at the portion subjected to the
irradiation with ultrasonic waves.
[0070] With respect to this specific example 2, the quantity of
penetration of vitamin C (quantity of ascorbic acids per 1 g of
skin) after the application of the whitening agent was measured on
a time basis. Moreover, for comparative purposes, with respect to
those samples that had not been irradiated with ultrasonic waves
(control 2) in the above-mentioned specific example 2 and those
samples to which the whitening agent was applied after a lapse of
one hour from the irradiation of ultrasonic waves, the quantity of
penetration of vitamin C was measured on a time basis. FIG. 6 shows
the results thereof.
[0071] As clearly indicated by FIG. 6, specific example 2 had a
greater accumulated quantity of penetration of vitamin C in
comparison with control 2 and those samples to which the whitening
agent was applied after a lapse of one hour since the irradiation
with ultrasonic waves, and in comparison with control 2 and those
samples to which the whitening agent was applied after a lapse of
one hour since the irradiation with ultrasonic waves, specific
example 2 had a greater quantity of penetration of vitamin C, and
it was found that those samples in which the medicine 1 was applied
to the skin surface 2a within 30 minutes after the application of
ultrasonic waves had higher penetrating effects for the medicine 1
and its active ingredient.
SPECIFIC EXAMPLE 3
[0072] After skin lotion (medicine 1) containing 5% of vitamin C
derivatives (magnesium ascorbyl phosphate) had been applied to the
entire portion of the face with cotton, ultrasonic waves were
applied to only the half portion of the face through a gel-state
ultrasonic wave transmission medium 25 without containing any
whitening component in the same manner as described above for 10
minutes. At this time, the irradiation conditions of the ultrasonic
waves were set as follows: frequency: 1 MHz, irradiation power to
the skin surface 2a: 0.5 W/cm.sup.2, probe area of the irradiation
unit 4: 4.52 cm.sup.2, and an output method for ultrasonic waves
(power): continuous output (duty ratio: 100%).
[0073] These operations were carried out almost every day, and the
results obtained 2 to 3 months later are shown in FIG. 7. FIG. 7
compares the change in the color of pigmentation between the half
of face (medicine+ultrasonic waves) to which both of the medicine 1
and ultrasonic waves were applied and the half of face (only
medicine) to which only the medicine 1 was applied, and the results
show that the color of pigmentation in the half of face to which
both of the medicine 1 and ultrasonic waves were applied becomes
brighter (whiter) in comparison with the half of face to which only
the medicine 1 was applied, to show higher whitening effects. In
other words, even when the medicine 1 was applied prior to the
irradiation with ultrasonic waves, penetrating effects of the
medicine 1 achieved by ultrasonic waves are sufficiently high.
* * * * *