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Патент USA US2403473

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2,403,473
UNITED STATES ‘PATENT OFFICE
Patented July 9, 1946
2,403,473
THERAPEUTIC COMPOSITIONS
Stefan Ansbacher, Rockville Centre, N. Y., as
signor to American Home Products Corpora
tion, New York, N. Y., a corporation of Dela
No Drawing. Application October 21, 1944,
Serial No. 559,827
4 Claims. (Cl. 167-65)
2
1
respond to medication with para-aminobenzoic
acid compositions of the present invention.
This invention relates to therapeutic composi
tions in which the active ingredient is para-ami- .
nobenzoic acid. It will be understood that the
term "para-aminobenzoic” acid is intended to in
clude water-soluble salts thereof such as sodium
5
para-aminobenzoate, calcium para-aminobenzo
ate, ammonium para-aminobenzoate and para
aminobenzoic acid hydrochloride. This applica
One object of the present invention is to pro
vide para-aminobenzoic acid compositions for use
in human therapy. Another object of the in
vention is to furnish a remedial composition for
the clinical treatment of syndromes such as
achromotrichia, endocrine disturbances,- gastro
intestinal disorders, which compositions may con
tion is a continuation-in-part of my co-pending
tain other therapeutically active ingredients such
patent application Serial No. 378,559 ?led Feb
as B-vitamins and/or natural or synthetic com
ruary 12, 1941.
pounds with endocrine activity.
Para-aminobenzoic acid was ?rst prepared by
According to my invention, a therapeutic com
G. Fischer in 1863 (Armalen, volume 127, page 142)
position is prepared in which para-aminobenzoic
by reduction of para-nitrobenzoic acid with am
monium sul?de. Up to the time of the present 15 acid is the predominant and primary active me
dicament and is contained in a solid substan
invention, however, there seems to have ‘been no
tially non-toxic medicinal carrier such as lactose,
direct application of para-aminobenzoic acid as
starch, sugar and dextrin together with other in
a medicament for human beings, the main use of
ert excipients used in the preparation of tablets,
the substance having been as a dye intermediate
and as a starting material for the preparation of 20 such as stearic acid, magnesium stearate, gelatin
and acacia. Preferably, however, the solid me
dicinal carrier is a vitamin B complex material,
the vitamin B complex materia1 being yeast, liver
local anesthetics, such as para-amino benzoyl di
ethylamino-ethanol. Since my publication of the
effect of para-aminobenzoic acid in preventing
or cereals, or mixtures thereof, or mixtures of
gray hair in rats in 1941 (Science, volume 93, page
164) and since the later publication of the success 25 synthetic vitamin materials, such as thiamine
hydrochloride, ribo?avin, nicotinic acid or its
accomplished in treating human achromotrichia
amide, with or without addition of the other B
with para-aminobenzoic acid, further investiga
Vitamins, such as pyridoxine hydrochloride, cal
tions have been carried out from the standpoint
cium pantothenate and inositol, or synthetic vi
of the treatment of certain syndromes frequently
occurring in the human being. These syndromes 30 tamin mixtures in the proportions found in nat
ura1 vitamin B complex products. In any case,
comprise achromotrichia with or without disor
however, the para-aminobenzoic acid is added in
ders related or not related to it, such as, for in
sufficient amount to constitute the chief thera
stance, endocrine, gastro-intestinal disorders, etc.
peutic ingredient, as for instance in tablets or
In some cases, it may be necessary to institute
proper therapy for the concurrent disorders be 85 capsules containing about 50 mg. to about 1, g. of
para-aminobenzoic acid.
The chromotrichial ei?cacy of para-aminoben
fore achromotrichial e?ects of para-aminoben
zoic acid become evident. In other cases, it may
zoic acid upon animals is shown by the follow
ing experiment. One hundred black or piebald
be possible to influence the concurrent disorders
solely by the administration of para-amoniben
zoic acid or by para-aminobenzoic acid in com
rats at weaning age, were placed on a basal ra
tion consisting of
bination with the therapeutic agents commonly
used in the treatment of such disorders.
_
The publications referred to above also stimu
lated investigations as to the amount of para
aminobenzoic acid inherently present in natural 45
sources of the vitamin B complex. It has sub
sequently been shown that natural vitamin B
cially achromotrichia and other syndromes which
Carbohydrate (for example Cerelose) ________________ __
giftaSmin-iree casein __________________________________ __
a
Soy been 011 __________________________________ ..
in extremely small amounts. To date, only one
sample of yeast has been found to contain as
much as 0.016% of para-aminobenzoic acid, and
this particular sample of yeast is about ?ve times
higher in para-aminobenzoic acid than most
other yeasts. Another vitamin B complex prod
uct is liver, the para-aminobenzoic acid content 55
of which is at least ten times lower than that of
weight
Agar ..... ._‘ ___________________________________ _.
complex products contain para-aminobenzoic acid
yeast. The low amount of para-aminobenzoic
acid inherently present in natural vitamin B com
plex materials is insu?‘icient to in?uence bene?
Parts by
Ingredient
Hydrogenated vegetable oil (for example Crisco)
Cod liver oil _________________________________________ _.
and given a daily supplement of 0.5 m1. of a 20%
ethanol solution containing per ml.:
Thiamine hydrochloride____ __micrograms__
Ribo?avin
do
Pyrodoxine hydrochloride __________ __do____
Calcium pantothenate _______ __milligrams__
Nicotinamide
'
do
Inositol
do
60 Choline chloride ...... -..-_---..-_...-_do..._-
80
80
80
1
1
1
6
9,408,478
When typical symptoms of achromotrichia had
by para-aminobenzoic acid in the form 01' the
composition of the invention when taken during
the periods 01 remission, and when taken in con
Junction with the usually employed remedies
appeared, seventy oi the rats were given an addi
tional daily supplement of 1 ml. oi’ a 20% ethanol‘
solution containing 3 mg./ml. oi’ para-amino
benzoic acid. A bluish discoloration oi’ the skin
(a typical ?rst sign of the normally pigmented
hair) appeared in 2~3 weeks and jet black hair
drug required.
within a month. The thirty controlled animals
in receiving the para-aminobenzoic acid con
acts by way 01' stimulation or inhibition of some
such as adrenalin or epinephrine during the at
tacks, thereby reducing the usual dose of the
It is also possible that para-aminobenzoic acid
tinued to show typical nutritional achromotrichia. 10 of the endocrine glands, such as sex glands,
Tablets consisting of 100 mg. of para-amino
adrenals, pituitary or thyroid glands. Thus, para
benzoic acid and a suitable amount of lactose
aminobenzoic acid by itself, favorably influences
have been administered clinically to numerous
abnormal basal metabolic rates such as in thyro
patients su?ering from achromotrichia in doses
toxicosis, either in the form of the composition
ranging from 50 mg. to a maximum of 600 mg. 15 of the invention'when taken in doses of 100 to 200
per day over periods of as long as two years and
mg. three to ?ve times daily or when taken in
nine months. Stoppage of further graying and
conjunction with substances usually administered
a partial and complete return of the normal color
tor the treatment of disturbed metabolism, there
of the hair has been reported for a fairly large
by reducing the usual dose of the drugs required.
number of the cases so treated. Thus, Dr. Ben 20 Thus, for instance, steroid hormones are poten
jamin F. Sieve has reported in 1943 in the Medical
tiated by the simultaneous administration of the
World, volume 62, pages 251-3, positive results in
the pigmentation of 82% of 460 patients of both
sexes treated for achromotrichia with the para
aminobenzoic acid tablets of the invention.
It is not known whether para-aminobenzoic
acid is to be classi?ed among the vitamins or
among some other therapeutically active agent.
para-aminobenzoic compositions of the invention.
I claim:
1. A therapeutic composition in dosage-unit
25 form comprising a carrier of the solid type and
as the added active medicament not less than
about 50 milligrams per dosage unit of a com
pound of the group consisting of para-amino
It is possible that para-aminobenzoic acid is ef
benzoic acid and water-soluble salts thereof.
fective by altering the bacterial ?ora within the 30
2. A therapeutic composition in dosage-unit
' gastro-intestinal tract. It is known that patients
form comprising a carrier consisting of the vita.
with constipation are relieved by the ingestion
min B complex and as the added active medica
of para-aminobenzoic acid in amounts of 100 mg.,
ment from about 50 milligrams to about 1 gram
three to ?ve times a day in the form of chocolate
per dosage unit of a compound of the group con
coated tablets of the composition of the invention, 35 sisting of para-aminobenzoic acid and water
or in oil emulsions, for instance mineral oil, or
soluble salts thereof.
any other media frequently employed in the ther
3. A therapeutic composition in dosage-unit
apy or prophylaxis of constipation with the aim
of reducing the usual laxative dose by the simul
form comprising a carbohydrate and as the added
active medicament from about 50 milligrams to
taneous administration of para-aminobenzoic 40 about 1 gram per dosage unit of a compound
acid.
of the group consisting of para-aminobenzoic acid
and water-soluble salts thereof.
acts by altering enzymatic processes occurring
4. A therapeutic, composition in dosage-unit
in the organism either by acting as a co-enzyme
form comprising a carrier of the solid type and
or by retarding certain enzymatic systems while 45 from about 50 milligrams to about 1.0 gram per
accelerating others. Thereby, the metabolism
dosage unit of a compound of the group consist
may be aiiected in such a manner that para
ing of para-aminobenzoic acid and water-soluble
aminobenzoic acid in the form of the composi
salts thereof.
tion of the invention in?uences endocrine dys
STEFAN ANSBACHER.
crasias. Asthmatics, for example, are bene?ted 50
It is also possible that para-aminobenzoic acid
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