CA1221139A - Method and device for stimulating growth and regeneration of hair - Google Patents

Abstract

METHOD AND DEVICE FOR STIMULATING GROWTH
AND REGENERATION OF HAIR

Abstract of the Disclosure Disclosed is an invention providing a method and a device for effect-ing electrotherapeutics.
More precisely, the invention provides an iontophoretic method for stimulating growth and regeneration of hair, comprising charging on the scalp a certain short pulse to introduce medicament into the scalp.
Also, the present invention provide a safe and economic device useful in the above method.
The medicaments preferred in the invention are certain photosensi-tizing compounds having a common amino vinyl structure, such as 2,2'[3'-[2(3-heptyl-4-methyl-2-thiazolin-2-ylidene) ethylidene] propenylene] bis [3-heptyl-4-methyl thiazolinium iodide], 2-[2-(3-heptyl-4-methyl-2-thiazoli-nium-2-ylidene) methine]-3-heptyl-4-methyl thiazolinium iodide, 6-[2-[(5-bromo-2-pyridyl) amino]vinyl]-1-ethyl-2-picolinium iodide, and 2-(2-anilino-vinyl)-3,4-dimethyl-oxazolinium iodide.
The short pulse usable in the invention is a low-frequency square wave superposed with a diphasic action potential wave.

Description

~2~ 3~
!

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-~r~

.

3~

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 .

.~

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~

~2;~L3~

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.~., -4~-mls/

~5~ ~2~3~

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 ~;~2~L~3~

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 ~Z~3ffl 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-. .

~:~2~3~

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.

-10~ 3~

.. ~

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 ~221~3~

, 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.

-13- 3 ~ 3~

, 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.

14- ~2~3~

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 _ ..

6 100 3,0 0,9 - 0,1 1.5 500 0.5 - 0,2 0O9 _ 1,000 _ 0.0 - 0,3 0,7 ~22~3~

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.

Claims (3)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A device for stimulating the growth and re-generation of hair, said device comprising:
a. an oscillator for generating a 0.5 - 2 Hz square wave having zero and positive potential;
b. an oscillator for generating a diphasic action potential wave with a pulse width of 200 - 600 seconds and pulse interval of 1/20 - 1/300 seconds;
c. a battery for supplying electric-energy to electric circuits;
d. first electrode driven by the oscillators;
e. second electrode maintained at ground potential from which the signals from the first electrode are referred;
f. an electric circuit for superposing the action potential on the low-frequency square wave; and g. a switch for coupling each oscillator and battery.

2. A device as set forth in Claim 1, wherein both oscillators are multivibrators.

3. A device as set forth in Claim 1, wherein the first and second oscillators are blocking oscillator and multivibrator respectively.