Note: Descriptions are shown in the official language in which they were submitted.
Elair grower
This invention relates to a hair ~rower which does not exhibit
undesirable side-effects such as systemic hormonal activity but
has an excellent hair growing effect by topical application.
Testosterone (male hormone) produced in the testicle and
adrenal gland is carried on the blood stream and reaches the
sebaceous gland where it is converted to 5~-dihydrotestosterone
(5~-DHT~, a more potent male hormone, by the reductase present
in the cells of the sebaceous gland.
Physiological symptoms such as male pattern baldness
(MPB) and seborrhea are said to develop as a result of
excessive androyen stimulation due to an excessive local
accumulation of testosterone.
Recently, the active form of male hormone in such organs
as che hair root and sebaceous gland has been identified to be
5~-DHT which is produced by reduction of testosterone in these
organs by an enzyme called testosterone-5~-reductase (briefly,
reductase). The me~hanism involved in the pathogenesis of
MPB may be postulated as follows. While 5~-DHT, which is
produced in the sebaceous tissue, combines with a receptor in
the sebaceous cells and ac-ts on the nucleus to promote the
growth of the cells, 5~-DHT itself comes out oE the sebaceous
gland cells and is carried on the blood stream and acts on
the nearby cells, i.e. hair matrix to inhibit division of the
hair matrix cells and prevent growth of the hair.
It is therefore believed that such conditions as male
pattern baldness or alopecia areata can be reduced or
~k
prevented by inhibiting the activity of the reductase and the
binding of 5~-DHT with the receptor protein in -the hair matrix.
From this standpoin-t, several substances have been discovered up
to date. However, none of these substances have proved to be a
satisfactory hair grower, because even i.f they have a high ra-te
of inhibition of the reductase activity, they usually have
undersirable side-effects or they show low rate of inhibition of
the binding of 5-DHT with the recepter protein.
In view of the above circums-tances, the present inventor
has made extensive investigations in order to search for a sub-
stance which has no undesirable side-effec-t such as systemic
hormonal activity, is safe, and show an effect of inhibiting
both the activity of the reductase and -the binding of 5~-DHT with
-the receptor protein by topical use. In other words, these
investigations have led to the discovery that the above object
can be achieved by employlng exendolone. The present inven-tion
was accomplished based on this discovery.
According to the present invention, there is provided
a hair growth enhancer preparation for topical treatment,
' comprising a maximum of about 2% by wei.ght of the total prepara-
tion of 16~-ethyl-17~-hydroxy-4-estren-3-one in admixture with a
topically acceptable, solid or liquid vehicle or carrier.
The present invention also provides a process for
producing a hair growth enhancer preparation for -topical treatment,
which comprises admixing a maximum of about 2~ by weight based on
the -total preparationof 16~-ethyl-17~-hydroxy-4-estren-3-one with
a -topically accep-table, solid or liquid vehicle or carrier.
' 'i''
Oxendolone, which is used in this invention, is chemical-
ly known as 16~-ethyl-17~-hydroxy-4-estren-3-one which is available
as a white or pale yellowish white, odorless powder. It is avail-
able on the market as a drug for benighn prostatic hypertrophy
and while it is administered intramuscularly as an aqueous
suspension containing 200 mg per 2 ml (Prostetin: Trade name of
Takeda Chemical Industries, Ltd., ~nited States Patent 3,856,829),
it has never been applied as a topical agen-t. The present hair
grower contains a maximum of about 2 ~ of oxendolone in combina-tion
wi-th a topically applicable vehicle or carrier, and if desired
with fur-ther usual additives. Preferably, the grower may contain
more than about 0.001 % of oxendolone and, more desirably, 0.05
to 0.2 % thereof in the total prepara-tion. Oxendolone is
practically insoluble in water but soluble, for example, in
e-thanol, and, therefore, aqueous ethanol containing more than
30 %, preferably 50 % of ethanol may be employed as a suitable
vehicle. Oxendolone also may be dissolved totally or partially
in vege-table olls such as sesame oil, cottonseed oil, castor oil,
olive oil, corn oil, peanut oil, etc., carbo-
- 2a -
~d~
-- 3 --
hydrates such as s~3ualane, squalene, liquid paxaffin, veseline,
etc., alcohols such as palmi~yl alcohol, hexadecyl alcohol,
stearyl alcohol, oleyl alcohol, propylene glycol, polyethylene
glycOl, polypropylene glycol, etc., fatty acids such as myristic
acid, palmitic acid, stearic acid, oleic acid, etc., or silicone
oils, lanoline, etc. The hair grot~er of the present invention
may optionally contain any of those additives normally used in
hair grower or hair tonics, for example germicides such as
hinokitiol, suxface active agents, refreshing agents such as
menthol, perfumes, antioxidants, ultraviolet absorbers, dyes,
moisturizers such as urea, salicylic acid, polyglyceride, gly~rol, etc.
The present hair grower may be used in the form of liquid as
well as emulsions, ointments, etc.,prepared by a conventional method,
and can be applied several times (1 to 6 times) a day in an amount
of about 0.5- 10 ml, preferably 1- 5 ml. However, the amount and
application interval may vary with the conditions of the subject
and may be used in a range of 0.1 mg to 100 mg per day, preferably
1 to 5 mg per day as oxendolone. In other words, the regimen of
this invention prescribes rubbing 0.05 ml/cm2 of the presen-t drug
well into the bare or downy patches of the scalp several times (1
to 6 times) a day. The grower is preferably used after a shampoo:ing.
It causes no particular side effect, but i-ts use is preferably
avoided in the presence of an open wound.
Toxicity Test of -the Present Hair Grower:
No loc~l acute toxicity was observed when 0.05 ml/cm of the
0.2 % ethanol solution of oxendolone was applied to the affected
area several times a day. However, frequent applications may
result in dryness of the hair and scalp, wher ethanol, etc. is
used. No other systemic or local side effect was observed in
the application schedule.
The systemic acute toxicity of oxendolone is as follows:
Acute Toxicity (LD5q- mg/kg)
. .,
Intramuscular Intraperitoneal
__ .
Mouse Male Above 10,000 2,930
Female Above 10,000 2,980
_
Male Above 10,000 6,530
Rat Female Above 10,000 5,880
~2~
-- 4
It is well known tha-t androgen is related to premature
baldness. To cure or arrest this condi-tion, it is important
to inhibit 5~-reductase activi-ty and 5~-DHT activity in the
sebaceous gland. It was found that "Oxendolone" of the present
hair yrower possesses not only the above two activities but
also the one to inhibit uptake of testosterone into the cells.
It was also found that -these activities of oxendolone, coupled
with the defatting actions of "ethanol", would synergistically
produce a decrease of head sebum and promote the mitosis of
basal cells of hair, rendering soft hair hard.
The effect of the oxendolone used in this inven-tion to
inhibit the activity of the reductase and the binding of
5~-DHT with the receptor protein will be described below by
citing a comparative example.
Inhibitory effect on the reductase activity
~ased on the method of Takayasu et al. ~The Nishinihon
Journal of Dermatology, 43, 1215-1217, 1981), the amount of
testosterone reduced to 5~-DHT was measured by using the
sebaceous gland at the back of a hamster. The concentrations
of the samples used in the experiment were 10 4 and 10 5 molar
concentrations, respectively. The rate of inhibition was
calculated from the following equation using the resulting data.
The results are shown in Table 1.
Rate of inhibition (~) = (C - t/C) x 100
C: the amount of 5~-DHT formed in a control
t: the amount of 5~-DHT formed when the sample was added
Table 1
. _. . __ _
~ _ Rate of inhibition
\ Molar __ _
Drug ~ ~r~ t~n 10-4 10-5
..
Oxendolone 43 + 18 ~ 28 ~ 28 %
.. ._ ~ ___
4-androsten-3-one-17 -54 ~ 32 % 31 ~ 19 ~
_
2~
Inhibitory effect of oxendolone on binding of 5~-DHT
with the receptor protein
_ _ .
Based on the method of Takayasu et al. (Arch. Dermatol.
Res., 264, 50-51, 1979~, the amount of 5~-DHT bound with
the receptor protein was measured. The concentration of the
sample used in the experiment was 10 6 molar concentration.
The rate of inhibition was calculated from the followincJ
equation using the resulting data. The results are shown in
Table 2.
Rate of inhibition (%) = (C - t/C) x 100
C: the amount of 5~-DHT bound with the receptor
protein in a control
t: the amourlt of 5~-DHT bound with the receptor
protein when the sample was added
Table 2
Chemicals Rate of
inhibition
.. . _ __
oxendolone 53 ~
~ .
4-andros-ten-3-one-17~- 0 ~
carboxylic acld __ _
It is seen from Tables 1 and 2 that while oxendolone has
an equivalent inhibitory effect on the reductase ac-tivity to
known 4-andros-ten-3-one-17~-carboxylic acid, its inhibitory
effect on the binding of 5~-DHT with the receptor protein
is greater, and that oxendolone can be said to be a substance
which achieves the object of this invention. Hence, it is
expected that the hair grower of this invention containing
oxendolone has a great hair growing effec-t.
The following examples illustrate the present inven-tion
in greater detail. The present inven-tion is not limited to
these examples. The amounts incorporated are % by weight.
Method of measuring the hair-growing efEect
It was evaluated by changes in the number of hairs lost
~uring hair washing before and after using the hair grower.
Ten subjects were used for each of Examples 1 to 3 and
Comparative Example 1. The period of measurement was 4 months.
In the first two months, the hair grower was not applied, and in
the latter two months, the hair grower was applied. The hair was
shampooed on every third day. The hairs which were lost were
collected once a week, and their number was counted. The number
of the lost hairs recovered eight times in total during the two
months in which period no hair grower was applied, and the number
of the lost hairs collected eight times in total during the two
months .in which period the hair ~rower was applied, were counted.
The number of the lost hairs for each time was indicated by
employing the symbol + and -. The effect was evaluated as shown
below from the difference between the average values of the two
periods.
The number of the lost hairs decreased by more
than 70, and a marked effect was observed.
+: The number of the lost hairs decreased by more
than 40, and a considerable effect was observed.
+: The number of the lost hairs decreased by more than
10, and it could be said that a little effect was
obtained.
-: The number of the lost hairs decreased by less than
10, and it could not be said that there was an effect.
The present invention will now be further described,
by way of examples only, with reference to the accompany drawings,
in which:
Figure 1 illustrates hair loss on the head of a 24 year
old female patient before treatment;
-- 6 --
~-4`'''
. 2~
Figure 2 illustrates the hair gain on the patient shown
in Figure 1, six months after initiation of treatment;
Figure 3 illustrates the anterior to lateral portions
of the calvarium of a 33 year old male patient before treatment;
Figure 4 illustrates hair gain on the patient of Figure
3, four months after treatment;
Fiyure 5 illustrates hair loss in the occipital and
parietal regions on -the head of a 36 year old female patient
before treatment; and
Figure 6 illustrates hair gain on the patient of Figure
5, one month after treatment.
Exampl_ 1 to 3 and Comparative Example 1
Chemicals Example 1 Example 2 Example 3 omparat ve
_
Oxendolone 0.001 0.2 2.0
95~ E-thanol 60.0 60.0 60.0 60~0
Deionized water 37 999 37.8 36.0 37.9
20 ~ Hardened castor
oil/40 mole E0 2.0 2.0 2.0 2.0
adduct
4-androsten-3-
one-17~- _ _ _ 0.1
carboxylic acid . . _ _ __
- 6a -
..~ .
-- 7 --
(Method of preparation)
Oxendolone or 4-androsten~3-one-17~-carboxylic acid and
hardened castor oil/40 mole E0 adduct were adcled to 95 ~
ethanol, and the mixture was stirred. Then, deionized water
was added to the solution and mixed to obtain a transparent
liquid hair grower.
-- 8
(Results)
Panel Period of Period of
No. Non-application Appl~cation Evaluat}on
1196 + 35 137 + 25
. = - _35~2 + 32- 294 + 51
3231 + 25 176 + 25
4156 + 25 172 ~ ~lO
Example ~ _
1 _ _369 -~ 51 281 -~ 57
6199 -~ 25 190 -~ 21
7-23-1 +- 29 17g + 44
8156 + 2~ 175 + Sl
. 9403 + 52 351 + 45
_ 10234 + 28 196 -~ 31
1183 ~ 45 141 + 36
2235 + 52 236 -~ 48
3 ~l32 + 36------ 353 + ~19
4 295 + 56 211 + 41
Example ~ _
2 5 33~ -~ 43 285 + 32
, 6 342--+ 70 260 + 52
7 345 + 51 301 ~ 42
8 365 + 40 215 ~ 37
9 412 -~ 42 365 -~ 40
. 10 259 + 25 201 ~ 31
_
Panel Period of Period of _ _
No. Non-application Application Evaluation
_ _ . . .
1 362 + 75 261 + 67 ++
_ _
2 234 ~ 32 l90 + 36 +
3 289 + 51 212 + 43 ++
. . _
4 361 + 42 296 + 33 +
Example _
3 5 412 + 54 365 + 45 +
. .. _ ~
6` 326 ~ 74 245 -~ 60 ~
. _ ~ .. __
7 296 + a6 241 + 38 ____
8 156 + 21 112 + 2S
_ . .
_9 _ 468 + 44 329 + 36 ++
. _ 1~ 325 -t 38- 285 -t 31
_ __
. 1 310 + 61 314 + 56 _
2 289 + 41 276 + 45
__ .. _. ..
3 ~21 + 26 379 + 36
tive 4 189 + 27 134 + 3
Example 5 261 t 48 273 + 46 . ___
1 . .. ~_ . ....
6 248 -t 26 239 + 29
. 7 ~62 + 43 419 + 38 _
. _ _ __ . . . __~_,
8 326 + 61 329 + 60 _ ~
. .___ . ._.
9 466 + 39 412 -~ 45
_ 10 24~ + 29 191 -t 31 ~ __ .
~ .. . _ _ _ _
~3 ~
-- 10 --
All the results given above show that the hair grower
in accordance with this invention containing oxendoione
has a better hair growing effect than the conventional
hair-preparation containing 4-androsten-3-one-173-carboxylic
acid.
Example 4
Hair-grower
2.0 g of polyoxyethylene (8 moles) oleyl alcohol ether,
0.05 g of oxendolone and 0.05 g of hinokitiol were added to
55.0~ of ethanol, per-Fume and dye were added in
suitable amounts. Then, 42.45 g of deionized water was added
-to the resulting solution to obtain a hair-grower.
When this hair-grower was used act-lally in the same way
as in Example 1, its superior hair-growing effect was
ascertained.
Example 5
Oxendolone (0.5 g), 2.0 g of polyoxyethylene ~60 moles)/
hardened castor oil, 10~0 g of glycerol, 10.0 g of dipropylene
glycol, 5.0 g of 1,3-butylene glycol, and 5.0 g of polyethylene
20 glycol 1500 were dissolved by heating at 60C (A). Cetyl
isooctanoate (10.0 g), 5.0 g of squalane, 2.0 g of vaseline and
2.0 ~ of propyl p-oxybenzoate were dissolved by heating at 60C
(B). 30.0 ~ of a 1% aqueous solution of carboxyvinyl polymer
and 0.03 g of sodium hexametaphosphate were dissolved in
25 3.35 g oE deionized water (C). A and B were mixed at 60C and
treated in a homomixer to form a gel. Deionized water (5.0 g)
was gradually added to the gel and the mixture was dispersed
by a homomixer. Then, C was added and finally a solution of
0.12 g of potassium hydroxide in 5.0 g of deionized water was
added. The mixture was emulsified by a homomixer to form
an O/W emulsion type hair-grower.
Example 6
Liquid paraffin (5.0 g), 5.5 g of cetostearyl alcohol,
5.5 g of vaseline, 3.0 g of glyceryl monostearate, 3.0 g of
polyoxyethylene (20 moles) 2-octyl dodecyl ether, 0.05 g of
vitamin E acetate, 0.3 g of propyl p~oxybenzoate and 0.05 g of
.
~2;~;~4~
a perfume were dissolved by heating. Then, a solution of
0~5 g of oxendolone, 7.0 g of glycerol, 20.0 g of dipropylene
glycol, 5.0 g of polyethylene glycol 4000, 0.005 g of sodium
hexametaphospha-te and ~5.095 g of deionized water obtained
by hea-ting was added. The resulting mixture ~as emulsified
by a homomixer to obtain a cream-like hair-grower.
Example 7
The following preparations were used in tne tes-ts ~ (22
MPB represents male pattern baldness.
Solution 1
Oxendolone 200 mg
70% ethanol 100 ml
Solution 2
. . _
Oxendolone 100 mg
70% ethanol 100 ml
Cream 1
Oxendolone 0.2 (weight ~)
squalane 15
stearic acid 3
stearyl alcohol 3.5
vaseline 2
stearyl monoglycelide 2
glyceline 5
propylene glycol 5
potassium hydroxide 0.2
butyl p-oxybenzoate 0~05
distilled water 64.05
100.00
(1) MPB; 32-year-old male, living in Kyoto City.
Prominent hair loss started 2 years ago, and marked hair loss
occurred during the summer to fall of 1981, causing recession
of the hairline in the anterior portions of the calvarium.
EIe was examined at the Department of Dermatolog~, Kyoto
University Hospital for about 2 months and was instructed to
apply about 2 ml of the solution 1 to the affected area once
a day at bedtime. As a result, the soft hairs in -the borders
became harder, and objectively also, the hairline at the
anterior portions definitely descended.
~ ppreciable hair loss was no longer observed. No side
effect was noted, either.
(2) MPB; 2~-year~old male, living in Kyoto City.
~e became aware in November 1980 that hair loss was on -the
increase and was treated by his local home doctor and at
Kyoto University Hospital without success. Then, in compliance
with the instruc-tion, he continued to rub about 3 ml of
the solu-tion 1 into the border of the hair in the anterior
portion once a day from the end of December 1~81. As a result,
descent of the hairline by about 5 mm was noticed in about
1 month.
In addition, there was an increase of soft hairs in
the anterior portions. He is under follow-up. No side
effect has been observed.
(3) Alopecia areata; 24-year-old female, living in Shiga Pref.
She noticed a patch of hair loss in the right lateral portion
of the calvarium in August 1981. Subsequently, hair loss
gradually spread over the entire scalp, and she was treated
by a local home doctor. However, as hair loss steadily
increased she was examined at the Department of Dermatology,
Kyoto Universi-ty Hospital on October 20 of the same year.
The diagnosis of a malignant type of alopecia areata was made
clinically and by biopsy, and she was treated for about
2 months. However, marked hair loss was persistent, advancing
to the degree where almost the entire scalp was bare.
Tentatively, application of about 5 ml of the solution 1 once
a day was attempted, and in about 1 month almost the entire
bare area showed regrowth of new soft hairs. In about one
month and a half, these soft hairs turned thick and black
in some portions. ~lard hairs appeared over the entire scalp
in about 2 months and recovered completely in about 6 months
(Figs. 1 and 2). In this case, the present solution 1 was
apparently so effective that improvement was obtained in
a markedly shorter period than the usual therapeutic course.
No particular side effect was noted.
,2~
- 13 -
(4) MP~; 33-year-old male, living in Kyoto City.
Hair loss has been increasing in the anterior to lateral
portions of the calvarium from the time when he was about
20 years old. After the age of 30~ hair loss seemed to
increase because of s-tress related to his job. On January 13,
1982 he was examined at the Department of Dermatology,
Kawabata Hospital with chief complaint of hair loss, accompanied
by an itching sensation. He was told to rub about 5 ml of
the solution 1 in-to the entire head once a day. As a result
of this therapy, decrease in hair loss and disappearance of
the itching sensation were noted in about 1 month and,
about 4 months later, he got well (Figs 3 and 4). No side
effect has been noted.
(5) Alopecia areata; 29-year old female, living in ~a~aokakyo
City.
She had been treated by her local doctor for annular erythema
of the face that used to appear around April annually.
A marked hair 105s occurred suddenly in the parietal portion
on December 17, 1981, and the entire head became almost
completely bare in about a week. She was examined at the
Department of Dermatology~ Kyoto University Hospital on
January 7, 1982. No mental problems, nor abnormalities of
the internal organs were observed. Because of disappearance
of some hairs from the eyebrow and soft hairs from the forearm,
the diagnosis of alopecia universalis was made. The solution 1
was prescribed for application of 5-7 ml over the entire
head once a day. After about one and a half month with this
regimen, growth of new roots of hair as black spots was noted
over the entire scalp and the soft hair has observed after
two months. No particular side effect has been observed.
(6) Alopecia areata; 45-year-old male, living in Shiga
Prefecture.
He had had an itching sensation of the head for about 20 days.
He noticed an increased hair loss 7 days previously and multiple
spots of hair loss about 4 days previously. On December 15,
1981, he was e~amined at the Department of Dermatology, Kyoto
Z2~
University Elospital. No mental stress, nor hematological
abnormalities were observed. Clinically, multiple alopecia
areata was suspected, and he was given a marketed hair grower
for local application. Hair loss was still present,
with formation o~ spots in a moth-eaten pattern. Since no
appreciable change was obtained after the lapse of one and
a half month, the solution 1 was prescribed for application
of about 4 ml to the affected area once a day. As a result,
hair loss was no longer observed 3 weeks later, and new growth
of soft hairs was noted in the parietal region, Eollowed by
complete recovery after 4 months. No side effect was observed.
(7) MPB; 36-year-old female, living ln Kyoto City.
After she had a permanent wave trea-tment of the hair around
1960, an irritating sensation was felt in the occipital region.
Then, she noticed the loss of the hair which gradually became
prominent. She left the condition uncured for a while, but
as the symptoms did not improve, she visited the Department
of Dermatology~ Kyoto ~niversity Hospital on January 19, 1982.
The solution 1 was prescribed for application of about 5 ml
over the entire head, especially at -the parietal region, once
a day~ In consequence, hair loss was reduced to a half in one
week, and there was no longer an appreciable loss of hairs
1 month later. In addition, the hair became thicker as a whole,
with an increased texture improvement. Thus, a definite clinical
improvement was observed (Figs 5 and 6). No side effect was found.
(8) MPB; 25 year-old male, living in Otsu City, Shiga Prefecture.
The hairline in the anterior region started to recede
at the age of 21. Hair loss seemed prominent in the fall to
winter season. He was examined at the Department of Dermatology,
30 Kyoto University Hospital on February 9, 1982. After he applied
about 2 ml the solution 1 to the anterior region once a day
fox about 1 month, growth of new soft hairs in the same region
became prominent. No side effect was observed.
(9) MPB; 22-year~old male, living in Kyoto City.
In the spring of l9S0, the hairline at both corners of
the forehead s-tarted receding. Then, hairs over the entire
~L~
15 -
anterior region began to decrease. There was a marked
dandruff in the balding area at the same time. He was
examined at the Department of Dermatology, Kyoto University
~lospital on September 3, 1981. Resorcinol and other lotions
were prescribed for application, but they caused no appreciable
change. From February 4, 1982 he used the solution 1 by
rubbing about 3 ml into the frontal to parietal region once
a day. As a result, he noticed an increaseof soft hairs in
the same region in about 1 month No side effect has been
observed.
(10) Alopecia areata; 36-year-old female, living in Shiga
Prefecture
Localized baldness, about 2 cm in diameter, was noted
in the occipital region in the beginning of June, 1981. She
was examined a-t -the Department of Dermatology, Shiga College
of Medical Science and treated without avail, the bald area
bei.ng rather increased. Then~ she visited the Department
of Dermatology, Kyoto University Hospital on February 4, 1982.
She was instructed to rub about 0.5 ml of the solution 1
into two localized bald areas once a day. Mild growth of new
soft hairs was noted in 2 weeks, and definite growth of new
soft hairs was observed over the entire bald areas after
another ~ weeks. Side effects have not been observed.
(11) Alopecia areata; ll-year-old female, living in Xyoto City.
In 1977, she was examined and treated at the Department
of Dermatology, Kyoto University Hospital for the hair loss
and baldness of the parietal region which had been persisting
for 2 years. Although treatment was continued, hair loss was
persistent and gradually expandiny- Although spontaneous
growth of soft hairs was then noted during a short spell of
time, hair loss beyan to icrease again in the summer of 1981
and did not improve. With a diaynosis of alopecia areata of
unknown cause, she was further treated at the Department of
Neurology, Kyoto Prefectural Colleye of Medicine. At the same
time, various tests were performed there, but no abnormality
was found. On February 2~ 1982 she was again examined at
z~
- 16 -
the Department of Dermatology, Kyoto University Hospital.
She applied about 4 ml each of the solution 1 twice a day,
in the morning and night. As a result, a mixed population of
soft and hard hairs began to ~row in about 1 month. No side
effect has been observed.
(12) MPB; 27-year-old male, living in Tokyo.
At the age of about 22 he became aware of an increasing
hair loss which used to be pronounced in the fall.
He left it untreated thinking that it was heredi-tary since
his fa-ther had also a typical senile baldness. When he became
27 years old, his hair looked so thin that the scalp in
the parietal region was exposed. On March 12, 1982 he was
examined at dermatological section of Ijinkai Takeda Hospital
through his brother's in-troduction. Examination revealed
only thinning of the hair in the parietal region with no
accompanying itching or dandruff,leading to the diagnosis of
MPB. Five ml each of solu-tion 2 was prescribed for application
to the parietal region twice daily As a result, the hair
loss which used to be about 100 hairs daily decreased to
20 about 60. On examination on September 17, 1982 regrowth of
numerous soft hairs was noted in the parietal region. No
local or systemic side effect has been observed.
(13) Alopecia area-ta, 29 year-old female, living in Hikone City,
Shiga Pref.
Remarkable loss o~ hair occurred in the parietal region
from the end of January 1982. In February, the diagnosis of
alopecia areata was made by a local dermatologist. Ointment
and medicine were administered for about one month, but
alopecia did no-t improve, hair loss expanding to the temporal
region bilaterally. Then, hormone injec-tion and another drug
for topical use were given, but no improvment was noted.
On April 5, 1982 she was examined at the Dept. of Dermatology,
Kyoto tJniversity Hospital. Hematological examinations were
all normal and no particular mental stress was found. The only
finding was a diffuse hair loss in the parietal region and
the bilateral temporal regions. For comparison, solution 1
and cream 1 were applied to right and left temporal area,
respectively. Two weeks later, while hair loss was persistent,
regrowth of new soft hair was noted over the entire areas of
hair loss. At 6 weeks, there was no longer hai~ loss, with
regrowth of numerous soft hairs. Alopecia areata completely
healed in about 3 months~ No particular differ~nce was found
between solution 1 and cream 1 but, regardiny applicability,
the patient had a better impression with -the solution.
(14) Alopecia areata,33 year-old female, living in Otsu Ci-ty,
Shiya Pref.
Hair loss round in shape, appeared in the parietal portion
in December 1980, and she was treated with ointment as well as
medicine at Japan Red Cross Hospital at Otsu. Since, in spite
of the treatment, hair loss continued, topical and oral steroids
were prescribed at the Dept. of Dermatology, Kyoto University
Hospital in January 1981~ She followed the instructions for
one month, but hair loss was still persistent. The treatment
was switched to an oral steroid alone. Then, hair loss
decreased in 2-3 months, and the oral steroid was suspended.
As a result, hair loss increased again r and in spite of
subse~uent various ways of treatment, no improving tendency
was noted. In January 1982, she started embrocating cream 1,
and a marked regrowth of soft and hard hairs was observed
in about 1-1/2 months.
(15) MPB, 32-year-old male, living in Kyoto City.
His forehead was rather wide from the birth, and hair
loss increased 2 years ago. In addition, recession of the
hairline in the frontal region was observed. His job was a
source of much stress, and hair loss was observed all the year
around, having the tendency oE increase when there was an
increase in dandruff~ He embrocated 2 g each of cream 1
prescribed at Kyoto Univ. Hospital into the borders of hairs
in the frontal portion once a day from June 1982. In about
one week, decreases in dandruff and in hair loss were noted.
At one month, regrowth of a few soft hairs was found in both
corners of the forehead.
i~ZZ~
- 18 -
(16) MPB; 52-year-old male, living in Kyoto City.
The hair in -the parietal portion was thin because of
the scar of a trauma he received in the head in his childhood.
For this reason he used -to use a wig. The hair from the
frontal to parietal portions became thinner as a whole about
5 years ago, and he was examined at the Dep~. of Dermatology,
Kyoto Vniversity Hospital on July 22, 1982. He received 2 g
each of cream 1 and embrocated it into the affected area 1-2
times a day. About one month later, a decrease in hair loss
and regrowth of soft hairs were observed. When he visited
the hospital about 4 months later his hair appeared thicker,
and he told us that hardly any hairs adhered to his wig any
more. He is under follow-up, and no side effect has been
seen.
(17) MPB; 60 years old, male, living in Kyoto City.
The subject noticed an increased loss of hair around 40
years old. He has tried various tonics sold on the market or
treated by a physician nearby. But no remarkable effect was
observed. During this time, the loss of hair extended ~rom
the forehead portion to the vertex portion, and he almost
gave up hope of recovery. When solution 1 was applied to him
in an amount of 5 ml once a day from June 1~82, soft hairs
newly grew in the Eorehead portion in about one month, and in
two months, soft hairs increased at the vertex portion. The
subject is now placed under observation for progress. No side-
effect has been observed~
18) MPB; 48 years old, male, living in Kyoto City.
Loss of hair has rapidly increased since 13 years agoj and
in the past 4 or 5 years, the hairs at the forehead portion
to the ver-tex portion became sparce. Almost all hairs have been
replaced by soft hairs. For this reason, the subject once used
a "wig" 7 or 8 years ago. He tried commercially available drugs,
but obtained no effect. Thus, he visited the Department of
Dermatology, Kyoto Uni~eersity Hospital for treatment. So
solution 1 was dispensed in an amount of 5 ml once a day. In
about one month, sof-t hairs newly grew in the forehead portion~
-- 19 --
and after a~out fur-ther three months, soft hairs grew in
the forehead portion to a visible extent.
(19) MPB; 32 years old, male, livlng in Kyoto City.
The subject noticed increasing i-tching and seborrhea at
the head, but left it without treatment. Soon, reddening
appeared in the forehead portion, and loss of hair increased.
Since the hairline at the forehead rose, he hurriedly began
to use 5 ml e~ch of solution 1 once a day in December 1981.
In about one month, reddening, itching and loss of hair
decreased, and in about 3 months, hard hairs were seen to grow.
He has continued to use solution 1. No side-effect has been
observed. This is a case of the inventor himself.
(~0) MPB; 52 years old, female, living in Kyoto City.
After death of a relative about 12 years ago, diffuse
loss of hair occurred. She then visited the Department of
Dermatology, Kyoto University Hospital. She used the dispensed
drug but no improvement was seen, Thereafter, she gave up hope
for recovery about loss of hair~ When she again visited the
Department of Dermatology, Kyoto University Hospital for
treatment, 5 ml of solution 1 was dispensed. In about
one week, itching at the head ceased, but no change was seen
in the amount of hairs lost~ In about 2 weeks, the amount
of hair lost was reduced to half~ and sof-t hairs were seen
to grow newly. About one month and a half later, the amount
of hair in the entire head increased, and the amount of hair
lost was about half of that before. When she visited the hospital
about 4 months later, the hair at the forehead evidently became
thicker.
(21) MPB; 37 years old, male, living in Kyoto City.
About one year and two months ago, the subject noticed
a large loss of hair accompanied by itching and a large amount
of dandruff. There was no mental stress. For this reason,
he visited -the Department of Dermatology, Kyoto Universlty
Hospital. The present solution 1 was dispensed. When he visited
the hospital about one month later, itching and dandruff de-
creased/ and the amount of hairs lost somewhat decreased.
~.~22~
20 -
~22) MPB; S9 years old, rnale, living in Ikoma City, Nara Prefecture.
About 5 years ago, dandruff at the forehead portion to
the vertex portion increased, and at the same time, loss of
hair began to increase. There was no particular mental stress.
For this reason, the subject began to use 5 ml each of solution 1
once a day in April 1982. In about one month, d~ndruff and loss
of hair were seen to decrease, and at the same time soft hairs
newly grew. He contirlued to use solution 1. Now, the scarce
portion of the hair at -the vertex became visibly black. There
was no particular side-effect~
(231 Summary of the Cases
MPB
Of the total 43 cases, 35(81~) were men and 8(19%) women.
The followin~ tables show the age distribution and duration of
illness,
Age Distribution:
-- .......... .. _ ~ . _ _. _ _ _ !
Age Number of Persons
_ _ . _ . _ . . ._
16 - 20 4 8.9
21 - 25 12 26.7
26 - 30 6 13.3
31 - 35 9 20.0
36 - 40 4 8.9
41 - 45 2 4.4
46 - 50 1 2.2
51 - 55 2 4.4
56 - 60 _ _ _ 6.7
Duration of illness:
3n Time (yëar) Number of Persons _
. ._ ~ _. _ _ .
less than 1 7 15.6
1 ~ 5 23 51.1
6 - 10 6 13.3
11 - 15 6 13.3
16 - 20 2 4.4
more than 20 _ _ _ ___ 2.2
21 -
Of -these cases, a definite effect observed in 32 cases
which are detailed below.
The duration until manifesta-tion of -the effect:
. . ........ _
TimeNumber of Persons %
_ __
1 - 2 weeks 3 6.7
3 - 4 " 3 6.7
1 - 2 months 14 31.1
2 - 3 " 4 8.9
3 - 4 " 6 13.3
more than 4 months . ~ .
. ~
Chanyes in individual symptoms:
Symptoms ¦Number of Persons %
1. Decrease in hair loss¦ 25 75.8
2. Regrowth of downy hairl 16 48.5
3. Regrowth of thick hai~ 7 21.2
4. Decrease in itching 6 18.2
sensation
5. Decrease in dandruff 3 9.1
6. Decrease in the sebum_ 3.0
Alopecia areata
This condition was observed in 41 cases consisting of
, 25 16 males (39 ~ and 25 females (61 ~). The aye distribution
and duration of illness are shown below.
Age Distribution:
AyeNumber of Persons . ,
30 1 10 2 4.9
11 - 20 10 24.4
21 - 30 7 17.1
31 - 40 11 26.8
41 - 50 6 14.6
3551 - 60 5 _ 12.2 .
~ 22;~
- 22 -
Duration of illness:
Time Number of Persons _ _
_ . . .
4 - 6 months 10 24.4
7 - 12 months 9 22.0
1 - 5 years 16 39.0
6 - 10 years 4 9.8
11 - 20 years 2 4.9
Of this population, the treatment was effective in
35 (85 ~). The following tables show the cluration until
manifestation of the effect and changes of individual symptoms.
Duration until manifestation of the effect:
Time Number of Persons _ .
_
less t.han one month 19 54.3
2 - 3 months 15 42.9
4 ~ 5 months _ 2.9
Changes of individual symptolns:
Symptorns of Persons __
. _
Regrowth of soft hair 33 94.3
~egrowth of -thick hair 10 28.6
Decrease in hair loss 6 17.1
Decrease in itching sensation 2 5.7
Increased perspiration 2.9
