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Патент USA US3051632

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United States
Patented Aug. 28., 1962
range ‘for adult humans is from about 300 mg. to 5.0 g.
per day but a single dose of about 0.5-1.0 g. produces
de?nite improvement. The de?nitive amount which is
Leo George Abood, Oak Park, Ill.
No Drawing. Continuation of abandoned application
Ser. No. 5,648, Feb. 1, 1960. This application Oct.
16, 1961, Ser. No. 145,427
3 Claims. (Cl. 167—-65)
actually administered will be determined by the attend
ing physician. He will be guided by the skills of his
art in prescribing an amount sufficient to attain normaliza
tion of the subject. These amounts are very low in view
of the extremely low toxicity of the N-benzoylpiperidine.
The low toxicity is exempli?ed by the fact that by oral
administration of 2.5 g. per kg. to rats, all test animals
remain in good health. However, at much lower doses
the normalizing elfect is apparent. In contrast to treat
ment involving other chemicals for relief of mental dis
turbances, no sedation, dizziness, impairment of motor
means and a composition dosage form.
function and coordination, or hypnosis is observed at
Mental disorders comprising the milder forms such as
anxieties, hallucinations, and hyperactivity, as well as 15 effective dosage levels. Furthermore, the subjects so
treated remain alert, have a general ‘feeling of improve
the severe stages of manic depression and schizophrenia,
ment, and show improved appetite and sleep.
‘are disturbances of the mind which have only recently
The effect of the new treatment is that of calming with
been attacked :by chemical means. vIn the last few years,
relief from axieties and hallucinations. The new treat
‘a number of new drugs have been introduced to relieve
the tensions by which most of these disturbances are 20 ment normalizes the severely disturbed subject and cre
The present invention relates to a treatment of mental
disturbances by chemotherapeutic means. More par
ticularly, it relates to a new method of treating certain
anxiety stages and similar mental tensions by chemical
caused. These drugs, commonly called tranquillizers,
are usually quite acceptable for certain types of dis
turbances, but in general, have very little e?ect on the
ates normal activity patterns for those subjects disturbed
by hallucinations: the restlessness and hyperactivity of
the patients are relieved, thus permitting integration into
normal life or full therapeutic programs.
severely disturbed mental patient. Furthermore, such
tranquilizers very often cause objectionable signs and 25 These effects can be observed in animals by a series
of tests such as initially developing mental stress by
symptoms in the patient such as depression, disinterest
modifying previously trained habit patterns and thereafter
in the surroundings, retreat from reality, and Withdrawal
administering N-benzoylpiperidine. Thus, the strain is
from activity.
A new method has now been found which, like the
placed on a habit pattern and is increased to a point at
tranquilizers, relieve anxiety stages and nervous disorders, 30 which certain objective signs of disquietude or other physi
cal imbalance can be observed and measured, and under
but, in contrast to the tranquilizers, has a calming effect
without causing mental depression. It reduces and in
such conditions the new treatment method may be tried
and studied.
some cases eliminates the outward signs of hostility and
paranoid tendencies evidenced by aggression, combative
To better illustrate the foregoing disclosure, reference
ness and belligerency and certain types of withdrawal 35 is made to the following examples which are not to be
and detachment engendered by hostility, without causing
considered the only applications of the new method
central nervous system depression or sedation, in men
tally disturbed human subjects in Whom the aforemen
tioned signs are evident.
This new e?ect is called a
Example 1
A sterile, aqueous solution of N~benzoylpiperidine is
The new treatment consists in ad 40 injected intraperitoneally into a group of rats at doses of
50 and 100 ing/kg. respectively. All test animals show
ministering to a mentally disturbed subject N-benzoyl
marked and prolonged muscle relaxation with diminish
piperidine in dosage form. The new method of treat
ing activity at the higher dose and hypersensitivity lasting
ment may be carried out with any dosage form, i.e.,
for about two hours.
desirable results may be accomplished by oral, intra
In a strain of extremely viscous rats, N-benzoylpiperi
venous, intramuscular, intraperitoneal, or subcutaneous
dine is administered intraperitoneally daily for four days
administration of the compound of the present inven
at doses of 100 mg./kg./day each. Complete elimina
tion. Obviously, in treatment of humans, the oral ad
tion of the combative viciousness is observed which re
ministration is preferred due vto its simplicity, whereas in
animal studies, administration by various injection routes 50 turns within 48 hours after the treatment.
is sometimes easier to control.
Example 2
normalizing effect.
N-benzoylpiperidine may be pressed into tablet form
A group of rats is ‘kept individually in activity measure
Tablets or
ment cages. These cages ‘are constructed in such a
capsules may include other non-toxic ingredients ordi
narily used for such preparations, e.g., ?llers, adjuvants, 55 manner that the animal’s movements produce oscillations
which are registered on a counter. The normal count
carriers, ?avoring agent, coloring agents, etc. ‘In case
of a healthy control rat averages about 100 in a ?ve
of tablets, any form of tablet coating may be selected,
minute period. After treating the rats with 5 mg./l<g.
but a sub-coating may be desirable in certain instances.
of the hallucinogen N-rnethyl-3-piperidyl-diphenylglyco
N-benzoylpiperidine may also be used for the various in
late, the animals become confused and hyperactive; their
jection routes together with physiologically acceptable
oscillator count for equivalent periods climbs from 100
solvents, diluents, carriers, etc. Solution concentrations
to about 1000. The injection of the hallucinogen is fol
of about 125 mg./cc. are best suited, although higher
lowed, after ?ve minutes, with the intraperitoneal admin
concentrations are acceptable with the more powerful
istration of 100 ing/kg. (0.00053 mol./kg.) of N
solvents. Lower concentrations are also useful ‘where
benzoylpiperidine to show complete recovery of the
N-‘benzoylpiperidine is less soluble in the solvent chosen
65 arti?cially caused hyperactivity.
and the required dose is small.
When the order of administration is reversed and the
The e?ective dosage for treating mental tensions and
hallucinogen injection follows the N-benzoylpiperidine
anxiety with N-benzoylpiperidine varies, of course, with
injection within ?ve minutes, no change in activity and
the degree of disturbance to be treated and the route of
habit pattern of the test animal is observed, demonstrat
administration selected. ‘In animals, the preferred amount
to be administered by intraperitoneal injection is between 70 ing the complete blocking action of the new treatment
to the effect of the hallucinogen.
about 125 and 550 mg./kg. The normal oral dosage
or it may be processed in gelatin capsules.
Example 3
evidenced by aggression, combativeness and belligerency,
and certain types of withdrawal and detachment en
An adult, human, male subject complaining of con
siderable anxiety and restlessness is given a single dose
gendered by hostility, without causing central nervous
system depression or sedation, in mentally disturbed
of 500 mg. of N~benzoylpiperidine in argelatin capsule.
Within two hours, the patient experiences a feeling of
relaxation and reports not having “felt this good in
weeks,” ‘although the subject had been on standard tran
quilizer treatment previously with Thorazine hydrochlo
human subjects in whom the aforementioned signs are
evident, comprising administering to said human subjects
a composition containing from about 0.3 g. to about 1.5
g. of N-benzoylpiperidine and a non-toxic pharmaceutical
ride (chlorpromazine hydrochloride).
2. The method of claim 1 wherein said composition
From the above examples, it will be seen that N 10 is administered to said human subjects at a rate of from
benzoylpiperidine has a typical tranquilizing eifect, ex
hibited by the calmness produced and the relief’ of anxiety
stages and hallucinations. Furthermore, it also shows
muscle-relaxing properties. This latter term relates to
the pharmacological e?fect on the central nervous system
which reduces skeletal muscle tensions without affecting
motor function and alertness. N-benzoylpiperidine thus ,
reduces muscle tension and counteracts hallucinogenic
0.3 g. per day to 5.0 g. per day.
3. A composition for reducing and in some cases
eliminating the ‘outward signs of hostility and paranoid
tendencies evidenced by aggression, combativeness and
belligerency, and certain types of withdrawal and de
tachment engendered by hostility, without causing central
nervous system depression or sedation, in mentally dis
turbed human subjects in whom the aforementioned signs
agents and the behavioral changes produced by such
20 are evident, comprising from about 0.3 g. to about 1.5 g.
of N-benzoylpiperidine and a non-toxic pharmaceutical
The action of Nabenzoylpiperidine on mental disturb
ances is quite surprising since, ordinarily, N-substituted
piperidine derivatives have no tranquilizing effect, and
if at all active, tend to be stimulating rather than tran
quilizing compounds. 'The new results achieved are
rendered more desirable because of the simplicity of the
treatment, the ease of administration, and the ready avail
ability of the compound.
This application is a continuation of my former appli
cation, S.-N. 5,648, ?led February 1, 1960, now aban
Others may practice the invention in any of the
References Cited in the ?le of this patent
Reppe ______________ __ Aug. 11, 1953
Bruce _______________ __‘_ Oct. 6, 1953
Good-win: The Pharm. 1., vol. 181, September 27, 1958,
pp. 233-235.
Drug Trade News, Mfg. Sec., vol. 33:18, September 8,
numerous ways which will be suggested by this disclosure
to one skilled in the art. All such practice of the inven
tion is considered to be a part thereof provided it falls
1958, p. 75.
within the scope of the appended claims.
30, 1958..
' '
' Modell: IAMA, vol. 167:18, pp. 2190-2l99, August
Chem. Abst. (1), vol. 38, 1944, p. 2651 5; (2), vol 37,
1043, p. 3750 1; (3), vol. 49, 1055, p. 2567 e; (4), vol. 47,
the outward signs of hostility and paranoid tendencies, 40 1953, p. 1700 b; (5), vol. 47, 1953, p. 2703 8.
I claim:
1. A method of reducing ‘and in some cases eliminating
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