Note: Descriptions are shown in the official language in which they were submitted.
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COMPOSITION USEFUL IN THE TREATMENT OF DIARRHEA
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a composition useful
for the symptomatic treatment for diarrhea. More
particularly the invention relates to a composition
useful for temporarily reducing the signs and symptoms
of diarrhea.
2 Background of the Prior Art
.
Diarrhea is present when movements of the
bowels occur with abnormal frequency and the total daily
bulk is abnormally large, the movements watery, foamy,
mucoid or blood-tinged. These derangements of colonic
function may be due to trivial or serious disorders; and
are frequent occurrences in people of all ages. Discomfort
in the abdomen often precedes, and painful anal spasm may
follow, the diarrheal movement. The causes of diarrhea
include improper diet, drugs, bacterial or parasitic
infection or infestation, organic disease, systemic
disease or disturbances of the personality and emotions.
Dextromethorphan is an old compound used here-
tofore as an antitussive. It is marketed in a wide
variety of "over-the-counter" (OTC) and prescription (Rx)
products for relief of cough, typically as the hydrobromide.
U.S. Patent No. 4,316,493 (Applicant's parent
application S.N. 140,493) discloses that dextromethorphan
is useful in the temporary reduction of pain. The
scientific basis of the discovery, while not fully
understood, is believed to be that dextromethorphan is
active on enkephalin receptors which have been associated
with pain.
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SU~A~Y OF THE INVENTION
An aspect of the present invention provides a
composition useful for temporarily reducing the signs and
symptoms of diarrhea in humans comprising an effective,
antidiarrheal amount of dextromethorphan or a pharmaceutically
acceptable salt thereof and a pharmaceutically acceptable
carrier.
Another aspect of the invention provides a process
for producing a composition as defined above, which comprises
admixing an antidiarrheal effective amount of dextromorphan or
a pharmaceutically acceptable acid addition salt thereof with
a pharmaceutically acceptable carrier.
DETAILED DESCRIPTION OF THE_INVENTION
Dextromethorphan (d-3-methoxy-N-methylmorphinan)
is well known in the art as a cough suppressant (antitussive)
and is commercially available; e~g., U.S. Patent No. 2,676,177
and Hafliger et al., Helv. Chim. Acta 39, 2053 (1956). The
hydrobromide salt of dextromethorphan is widely commerically
used as an "over-the-counter" (OTC) orally administered anti-
tussive. It is also used as an antitussive in combination with
antihistamines and decongestants in prescription (Rx) products
for cold remedies.
Dextromethorphan may be used in the present
invention in daily dosage amounts between about 5 mg and
1,000 mg and preferably between about 10 mg and about 500 mg
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depending on the age and weight o the person and the severity
of diarrhea to be treated. A typical daily dosage amount
suitable or a human varies between about 10 mg and about 300 mg
and preferably between about 20 mg and 200 mg. For example, a
typical dosage amount of dextromethorphan hydrobromide effective
in temporarily
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reducing the signs and symptoms associated with diarrhea
in an adult human would be about 20 mg to about 50 mg
administered in equal doses 1 to 4 times per day.
For therapeutic use, dextromethorphan will
normally be administered as a pharmaceutical composition
in the basic form or in the form of an addition salt with
a pharmaceutically acceptable acid and in association
with a pharmaceutical carrier therefor. Such addition
salts include those with hydrochloric, hydrobromic,
hydriodic, sulphuric and maleic acids and preferably
hydrobromide.
Other pharmacologically active compounds known
to be useful in the treatment of diarrhea may, in certain
cases, be included in the composition including, for
example, kaolin, pectin, bacterial cultures such as
Lactobacillus acidophilus and L. bulgaricus, bismuth
subsalicylate, bismuth subnitrate and calcium hydroxide
and attapulgite. Advantageously, the composition will be
made up in a dosage unit form appropriate to the desired
mode of administration, for example, as a tablet, capsule,
sustained release type, oral suspension, or in a suitable
formulation for conventional or sustained release topical
administration.
The pharmaceutical compositions may be in a
form suitable for oral use, for example, as tablets,
lozenges, aqueous or oily suspensions, dispersible
powders or granules, emulsions, hard or soft capsules, or
syrups or elixirs. Compositions intended for oral use
may be prepared according to any method known to the art
for the manufacture of pharmaceutical compositions and such
compositions may contain one or more agents selected from
the group consisting of sweetening agents, flavoring
agents, coloring agents and preserving agents in order to
provide a pharmaceutically elegant and palatable
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preparation. Tablets contain the active ingredient in
admixture with nontoxic pharmaceutically acceptable
excipients which are suitable for manufacture of tablets.
These excipients may be inert diluents, for example
calcium carbonate, sodium carbonate, lactose, calcium
phosphate or sodium phosphate; granulating and disintegra-
ting agents, for example, maize starch, or alginic acid;
binding agents for example, starch, gelatine or acacia,
and lubricating agents, for example, magnesium stearate
or stearic acid. The tablets may be uncoated or they may
be coated by known techniques to delay disintegration and
absorption in the gastrointestinal tract and thereby
provide a sustained action over a longer period.
Formulations for oral use may also be presented
as hard gelatine capsules wherein the active ingredient
is mixed with an inert solid diluent, for example,
calcium carbonate~ calcium phosphate or kaolin, or as
soft gelatine capsules wherein the active ingredient is
mixed with an oil medium, for example, arachis oil,
liquid paraffin or olive oil.
Aqueous suspensions contain the active
ingredients in admixture with excipients suitable for the
manufacture of aqueous suspensions. Such excipients are
suspending agents, for example, sodium carboxymethyl
cellulose, methylcellulose, hydroxypropylmethylcellulose,
sodium alginate, polyvinylpyrrolidone, gum tragacanth and
gum acacia; dispersing or wetting agents may be a naturally
occurring phosphatide, for example, lecithin, or conden-
sation products of an alkylene oxide with fatty acids, for
example, polyoxyethylene stearatet or condensation
products of ethylene oxide with long chain aliphatic
alcohols, for example heptadecaethyleneoxycetanol, or
condensation products of ethylene oxide with partial
esters derived from fatty acids and a hexitol, for
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example, polyoxyethylene sorbitol monooleate, or condensa-
tion product of ethylene oxide with partial esters
derived from fatty acids and hexitol anhydrides, for
example, polyoxyethylene sorbitan monooleate. The said
aqueous suspensions may also contain one or more preserva-
tives, for example ethyl- or n-propyl- p-hydroxy benzoate,
one or more coloring agents, one or more flavoring agents
and one or more sweetening agents, such as sucrose,
saccharin, or sodium or calcium cyclamate.
Dispersible powders and granules suitable
for preparation of an aqueous suspension by the addition
of water provide the active ingredient in admixture with
a dispersing or wetting agent, suspending agent and one
or ~.ore preservatives. Suitable dispersing or wetting
agents and suspending agents are exemplified by those
already mentioned above. Additional excipients, for
example, sweetening, flavoring and coloring agents, may `
also be present.
Syrups and elixirs may be formulated with
sweetening agents, for example glycerol, sorbitol or
sucrose. Such formulations may also contain a demulcent7
a preservative and flavoring and coloring agents.
The pharmaceutical compositions may be tableted
or otherwise formulated so that for every 100 parts by
weight of the composition there are present between 5 and
95 parts by weight of the active ingredient and preferably
between 25 and 85 parts by weight of the active ingredient.
The dosage unit form will generally contain between about
10 mg and about 500 mg of the active ingredient of the
formula stated above.
From the foregoing formulation discussion, it
is apparent that the composition of this invention is
preferably administered orally.
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The scientific basis of the discovery set forth
herein is not fully understood; however, it is believed
that dextromethorphan is able to exert its antidiarrheal
activity by acting upon specific enkephalin receptors in
the body, in particularly in the gastrointestinal area.
Enkephalin receptors are believed to be associated with
hypermotility and associated distress of the gastrointes-
~inal tract, a causative factor in diarrhea.
