Note: Descriptions are shown in the official language in which they were submitted.
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!
Field of the Invention
I'he present invention relates to a method and a dev;ce for electro-
therapeutic, particularly, it relates to an iontophore~ic method for stimu-
lating growth and regeneration of hair and a device useful in the above
method .
Descr ption_of the Prior Art
Various chemical and physical attempts including electrotherapeutics
have been applied to alopecia. Rapid and complete treatment in many
alopecia symptoms i5 very difficult because their causes are still not clar-
. .
ified. Even though treatment is effective, several weeks or years are,however, required for complete treatment. The complicated etiology o
alopecia has obstructed the establishment of a definite therapeutic.
Recent studies on alopecia resulted in encouraging findings that the
symptoms of persistent alopecia seem to be very similar to that of tempo-
rary alopecia, and that the changes in the scalp conditions affect the
growth and regeneration of hair from the hair follicles. Generally, hair
follicles do not vanish until one' s death .
Accordingly, one can expect a certain means for stimulating the hair
follicles to well effect a substantial growth and regeneration of hair.
Some electrotherapeutics are disclosed in patent applications, wherein
hair follicles are stimulated by charging on the scalp a low-frequency dc-
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or modulated dc-current, e. g ., square or saw-tooth wave, to accelerate
growth and regeneration of hair.
A typical method is disclosed in USP No.3,872,859 (A. Sylvester et
al. ) ~ which comprises successively positioning a pair of electrodes in a
spaced relationship against predetermined areas of that portion of the scalp
overlaying the galea, passing electrical current between said electrodes
wherein said current is in the form of a low-frequency wave in the range
of 200 to 3 ,000 Hz, with an electrical potential sufficient to stimulate said
organs; and massaging said scalp in the area of at least one of said elec-
trodes .
Although the electrotherapeutic approach of the method deserves
appraisal, the method is insufficient to completely treat alopecia by the
following reasons: Charging of such dc current to the skin inevitably
effects deep electric-burn to form undesirable vesicles, bulla and redness
of the skin. Continuous or continual charging of such current makes a
patient very unpleasure due to its inadequate waveform, thus the treatment
cannot be continued until satisfiable effect will be obtained. Furthermore,
electrotherapeutics for stimulating growth and regeneration of hair using
only a low-frequency wave have a limited efficacy.
Accordingly, there have existed a strong need for a convenient and
effective method for stimulating growth and regeneration of hair. As will
become apparent from the following, the present inven1:ion does satisfy the
need .
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3~
SUM~ F TEIE I~`]VEN'rION
According to an aspect of the invention there is
provided a method for stimulating yrowth and regeneration of
hair, which comprises char~ing on the scalp a dc current,
superposed with a diphasic action potential wave, with a
potential level sufficient to effect iontophoresis of a
photosensitizing amino vinyl compound.
According to a further aspect of the invention
there is provided a device for stimulating the growth and
regeneration of hair, the device comprising: an oscillator
for genera'ing a 0.5 - 2 Hz square wave having zero and
positive potential; an oscillator for generating a diphasic
action potential wave with a pulse width of 200 - 600 seconds
and pulse in-terval of l/20 - l/300 seconds; a battery for
supplying electric--energy to electric circ~lits; first
electrode driven by the oscillators; second elec~rode ~.ain-
tained a-t ground potential from whlch the signals .FrorL the
firs-t electrode are referred; an electric circuit for s~lper-
posin~ the action potential on the low-Erecuency square ~ave;
ancl a ~witch for coupling each osci.llator and the ha-tter~.
B_IEF DESCN P 0~ OF THE 3R~'1NGS
FIG. l. shows a hloc~-diagram of a device for
st:i.m~lla-tin~ growtll ancl regeneration of hair accordinq to the
invention.
F'IG. 2 sho~s the waveforms of the de~ice of
FIG. i, wherein FIG. 2(a), (b) and (c) ~ive the out~ut
waveforms ~enerated by -the first and second oscillators,
t~
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and -the superposed square ~ave, respectiyely.
FIG. 3 sho~-Js an electric c.ircuit of a device
according to the invention usincf two multivibra-tors 1 and
2 as the first and second oscillators.
FIG. 4 shows an elec-tric eircuit of another
device accordi~g to the invention usiny blockincr oscillator
1 and multivibra~or 2 as the firs-t and second oscillators,
re~pectively.
. FIG 5, on the same sheet as FIG. 1, shows -the
junetion of two higllly-reliable 10~7-frequency oscillators
and the synchroscope as used in EXPERIMENT 2.
~ ouc3h ~IGs. 1 to 5, Osel is the first oseillator;
Ose2, seeond oscillator; 3 and 4, terminals; 5, sponge roller-
type electrode; 6, ground electrode; C, capacitor; R, resistor;
S, switch; Sy, synchroscope; T, transformer; E, earphone jack;
and Tr, transistor.
Desc_iption of Preferred Embodiments
The present inven-tion is based on the finding that iontophoresis
~0 of eertain amino vinyl compounds into the scalp, using a low-
frequency square wave superposed with a diphasie acti.on potential
wave, results in a remarkable yrow-th and regeneration of hair
without undesirable af-ter~effec-ts; and that such ion-tophoresis to
-the skin on other sites of the body, e.~.,
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mls/
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hand, leg or face, remarkably removes the pigment deposited therein,
especially, melanin pigment.
Also, the present invention is based on the finding that such ion-
tophoresis can be carried out safely and economically with the use of a
device comprising: an oscillator for generating a 0 . 5 - 2 Hz square wave
having zero and positive potential; another oscillator for generating a
diphasic action potential wave with a pulse width o~ about 200 - 600 se-
conds and a pulse interval of about 1/20 - 1/30 seconds; a battery for
supplying electric-energy to electric circuits; first electrode driven by the
oscillators; second electrode maintained at ground potential from which the
signals from the first electrode are referred; an electric circuit for
superposing the action potential on the low-frequency square wave; and a
switch for coupling each of oscillator to the battery.
. ~ .
The amino vinyl compounds preferred in the invention are certain
photosensitizing dyes which have a common vinyl structure bearing N-
hetero aromatic-ring(s) at 1- and/or 2-position(s); one or more of the
aromatic-rings are quarternary ions associated with halide. Said photo-
sensitizing dyes generally have strong UV-absorption bands, and exhibit
specific colours. Commercially-available amino vinyl photosensitizing dyes
are 2, 2 ' [ 3 ' - [ 2- ( 3 -hep tyl-4-methyl-2 -thiazolin-2 -ylidene ) ethylidene prop enyl-
ene] bisl3-heptyl-4-methyl thiazolinium iodide] (Kankoh-so No.101), 2-[2
t3-heptyl-4-methyl-2-thiazolin-2-ylidene) methine]-3-heptyl-4-methyl thia-
zolinium iodide (Kankoh-so No.201), 6-12-[(5-bromo-2-pyridyl) amino vinyl]-
l-ethyl-2-picolinium iodide (Kankoh-so No.301), and 2-(2-anilinovinyl)-
3,4-dimethyl-oxazolium iodide (Kankoh-so NoO401), products of Japanese
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Research Institute for Photosensitizing Dyes Co., Ltd., Okayama, Japan,
are all advantageously feasible in the invention.
Prior to its use, the amino vinyl compound is ~ generally, dissolved in
an alcoholic saline solution to give a concentration of about several ten to
several hundred ppm. Then, the solution is directly applied on the af-
fected site of the body, or allowed to absorbance in or on a sponge roller-
type electrode. Thereafter, the low-frequency square wave, superposed
with a diphasic action potential wave, is charged on the site to effect ion-
tophoresis of the compound through the skin.
The action potential wave, as referred to in the SPECIFICATION, shall
be a diphasic short pulse having a similar waveform as generally observed
in the normal rnuscles upon the expansion and contraction of the muscule:
The short pulse alternates synmetrically against the tim~-axis with a pulse
width of about ten milliseconds. The short pulse transmits the informa-
t~ons, which occurred in the stimulated sites of the muscle, to the brain
via nerves.
The low-frequency square wave to be charged can be generated by
superposing a diphasic action potential wave, frequency of about 50 - 300
Hz, on a square wave having zero and positive current components, fre-
quency of about 0 . 5 - 2 Hz . In case objective is to remove the deposited
pigment, the superposed square wave can be replaced with a diphasic
action potential wave which alternates at a positive potential line slightly
lower than its wave-height with a pulse interval of about 1/10 - 1/200
seconcls and a pulse width of ahout 1/100 - 1/500 seconds.
The superposed square wave may be generally charged on the affected
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site with about several volts to several ten volts, or 0.1 milliampere to 10
milliampere, but should be carefully controlled in the above described range
to meet the conditions of the affected site or the patient's symptom. De-
pendent upon the patient's symptom, a treatment can be carried out pro
perly as follows: For example, a small portion of a methanolic saline sol~
ution of the amino vinyl compound, concentration of about l0 - 1,000 ppm,
is directly applied on the afected sit~, or absorbed in a sponge roller-type
electrode, prior to treatment. Then, the superposed square wave is charg-
ed on the site for several minutes or several ten minutes to effect
iontophoresis of the compound~ While monitoring the progress of the
treatment effect, i.e., growth and regeneration of hair or removal of the
deposited pigment, the above described procedures may be carried out once
or more a day.
One or more agents or nu trients 9 such as acetyl choline, steroid,
sugar, protein, amino acid or vitamin, may he introduced together with the
àmino vinyl compound: Iontophoresis of the amino vinyl compound in
combination with certain sugar or protein, e.g., glucose or serum, may
effect further effective treatment.
The following description will explain the device feasible for the
iontophoretic treatment according to the invention.
FIG.1 illustrates a device according to the invention, wherein Oscl is
the first oscillator which generates a diphasic action potential, pulse in-
terval of about 11200 - 1/600 seconds, pulse width of about 1/20 - 11300
seconds, as shown in FIG.2ta), and wherein Osc2 is the second oscillator
which generates a square wave having zero and positive current compo-
. .
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nen$s, freguency of about 0.5 - 2 Hz, as shown in FIC~.2(b).
The square wave is superposed with the action potential wave to
obtain the low-frequency wave adequate for the present objectives (FIG . 2
(c) ) .
The positive region of the superposed sguare wave, i.e., K - L, and
another region alternating around ~ero-volt line , i . e ., L - M , are effective
for iontophoresis of the amino vinyl compound and electric massage of the
~kin respectively.
The superposed square wave thus obtained is charged on the skin
with the uses of a sponge roller-type electrode 5 (the first electrode), and
the second electrode 6 (maintained at ground potential from which the
signals from the first electrode are referred) through the terminal pair 3
and 4.
. ~ .
FIG . 3 illustrates the electrical circuit of a practical device according
to the invention . In this device ~ a blocking oscillator and a multivibrator
are used as the first and second oscillators to generate the action potential
and square waves respectively. The action potential wave is charged
through the primary coil of transformer T to the terminal 3, to which the
sponge roller-type electrode is connected.
On the other hand, the low-frequency square wave with ~ero and
positive current components, frequency of about O . 5 - 2 H~, generated by
the multivibrator, i5 introduced to an emitter-follower clrcuit, constructed
with transistor Tr4, to reduce its output impedance. The output current
is then charged to the secondary coil of the transformer, and superposed
therein with the action potential wave. The battery B2 biases the tran-
3~
sistor .
FIG . 4 illustrates another device according to th~ invention, whereintwo CR-multivibrators are used as the first- and the second oscillators.
- The square wave, generated by the first multivibrator 1, frequency of
about 50 - 300 Hz, is differentiated by the circuit, constructed with ca-
pacitor C9 and resistor R15, to obtain an action potential wave, as shown
in FIG.2(a), which is then superposed on the low-frequency square wave,
frequency of about O . 5 - 2 Hz, generated by the other multivibrator 2, to
give the ob]ective superposed square wave as illustrated in FIG . 2 (c~ . The
superposed current is feasible for the iontophoresis of the amino vinyl
compound according to the invention.
The superposed square wave is charged to a pair of electrodes 5 and
6 through the terminal pair 3 and 4.
Capacitor C12 repeatedly charges and discharges the square wave
current, generated by the second multivibrator 2, through the resistor R19
to suppress the distortion of the wave: thus, the waveform of the output
current at the capacitor C12 becomes genuinely square.
The surprising therapeutic effects by the invention will be embodied
by the following EXPERIMENTs.
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EXPERIMENT 1
.. ~
In the device, as shown in FIG. 3, the pulse interval and width of
the action potential, generated by the blocking oscillator (the first-oscil-
lator), were se-t at 1/50 and 1/200 seconds respectively. The frequency of
the multivibrator (the second-oscillator3 was set at 1 H~.
Prior to the experiment 9 hair of some groups of rabbits were removed
by applying bisynmetrically silver cream on 4 places, about 5 cm2 each, of
their dorsum area, and the places were allowed to a brief standing, and
then washed carefully not to wound the animals.
The first group of ~he animals was applied with either acetyl choline
. .
in glycerine, or an amino vinyl compound solution, prepared by dissolvin~
in saline Kankoh-so No.301 or 401 to give a concentration of 0.05 %, and
adrnixing the mixture with 0.5 parts of 95 ~6 alcohol9 and then charged for
10 minutes with the superposed square wave with the use of the device for
10 minutes once a day ~Group A).
The second group of the animals was treated similarly as above,
except that in place of the superposed wave a saw-tooth wave, frequency
of 3,000 Hz, was charged to the animal with the use of conventional device
( Group B 3 .
The third group of the animals was also treated with each preparation
without subsequent charge of the electrical wave (Group C~.
The fourth group of the animals was used as control, to which neither
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the agent was appled nor the electrical wave was charged (Group D).
In the course of the experiment, the hair was shaved 10, 20, and 30
days after starting the experiment, and the le~gths of the 100 bristle were
microscopically measured. The averaged results are given in TABLE I.
The resuits confirm that the growth and regeneration of hair are
slightly accelerated by applying the amino vinyl compound on the skin, and
is significantly enhanced by combined charge of the square wave super-
posed with an action potential wave. ~lso i5 confirmed that the stimulation
attained by the combination of the compound and the superposed square
wave is superior than that attained with the use of conventional saw-tooth
wave .
. ~ .
TAB~E I
Agent .
~ Kankoh-so Kankoh-so Acetyl choline
Treatment ~ No. 301 No. 401
_ _
10 days 10 . 2 9 . 5 5 .1
_ . ... __
A (mm) 20 days 26 . 7 22 . 2 13 . 2
30 days 42 . 4 34 .1 17 . 2
3~
__ _ .. ~ . . .
11) days 6.5 5.3 4.9
. . ....... _
B(mm) 20 days 17 . 2 16 . 2 12 .1
_ . ~ ~ .
days 25 . 3 24 . 8 15 . 7
_____. _ .=._.
days 5.8 4.5 4.1
~ ^;.' ~ _
C~mm~ ': ~ ~ 20 days 16 . 4 13 .1 10 . 8
. , ::_
. . 30 days 22 . Q 19 . 2 15 . 5
._ ___ ~ __
o 10 days 2.9 1.6 3.0
l _
D(mm) 20 days 8.7 9~9 5~8
. . ~ . . . __ ._ _
. 30 days 15 . 8 16 . 6 11. 6
. ._
Note: A, wherein the iontophoresis of the agent was effected with the
use of the device according to the invention; B, wherein the iontopho-
resis of the agent was effected with the use of a conventional device;
C, wherein the only agent was applied on the skin without subsequent
charge of the electrical current; and D, wherein neither application
nor iontophoresis was used.
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EXPERIMENT 2
,
Superposed square wave
Two highly-reliable low-frequency oscillators, Oscl and Osc2, were
junctioned with a synchroscope Sy as shown in FIG. 5, and the superposed
current was charged through the terminal pair 3 and 4 between positive
and negative electrodes 5 and 6, whila observing the waveform with the
synchroscope .
The preferable frequency ranges of Oscl and Osc2 were determined in
a manner similar as in EXPERIMENT 1, except that their frequencies were
varied as shown in TABLE II, and that 200 ppm Kankoh-so No.301 in an
alcoholic saline solution was used as the amino vinyl photosensitizing dye.
. .
The results are given in TABLE II.
These results confirm that the possible highest stimulation of the
growth and regeneration of hair are attained when the frequencies of the
square wave, generated by the oscillator Oscl, and of the action potential,
generated by oscillator Osc2, are about 1 Hz and from about 50 Hz to about
200 Hz respectively.
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TABLE II
. ~
A - B
(Averaged mm)
No. Frequency of Frequency o:f
OSC1 ( H5 ) SC2 ( Hz ) _
. 10 days 20 days30 days
. . .
1 1 - 0.5- 0.2
` 2 5 3,2 3.~
1 100 0,11,9 4,15,2
500 1,0 2,22.0
1,000 0,8 1,1- 2,2
_ . _
- 0,3 ~.9 1,7
3,1 6,2 7,8
2 100 0,5 2,7 5.8 8,1
500 1.9 3,5 2,8
1,000 1.6 - 1,4 0.0
_ _
.~ 5 1.8 1,6 - 2.1
~.5 9,3 1~.2
3 1~0 1,0 5.1 11.1 17.4
500 2.8 4,5 8,5
1,000 0.8 1,1 1,2
_ . _
- 1.1 0,1 - 0,2
3,1 6,7 7~8
4 100 1,5 3.2 5,8 6,3
500 1,2 2,3 3,2
1,000 - 0.8 - 0,2 0.7
__ _ _
- 0.1 - 0,2 1.0
2.1 3,6 4,0
100 2,0 1.9 2,8 3.1
500 0.8 1,5 1,1
1,000 - 0,7 0,4 0,2
_ ..
- 01 51 - 2 21 2 2
6 100 3,0 0,9 - 0,1 1.5
500 0.5 - 0,2 0O9
_ 1,000 _ 0.0 - 0,3 0,7
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No-te: ~ shows the averaged length of bristles obta3inea
according to the invention; and B, that obtained in the control
(mm) .
Based on the above confirmations, the present
iontophoretic method was applied to various alopeci~ patients
using Kankoh-so No. 301 and 401. Satisfiable treatments were
attained in alopecia areata, alopecia praematura,alopecia
pityrodes and alopecia a-trophicans.
The high efficacy according to the pres~nt inven-
tion can be interpreted as follows: In comparison wlth con-
ventional agents, the amino vinyl compound is far m~e
effec-tive in stimulating growth and regeneration of ~!air.
The action potential, superposed on the square wave, effectively
interacts wi-th nerves to restore them from fatigue, as well
a.s acceleratinq the skin metabolism.
Thus/ the eEfective mental and physical '.:Leat-
metl-ts can be simultaneously attained.
Wl1i.le a particular :Eorm of the in~ention has been
i.llustrated and clescribed, it is apparent t:at ~ario~., moc~ Ei-
cations can be made without departing from the sp.iri.t ~.nd
scope o- -the i.nven-tion.
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