Note: Descriptions are shown in the official language in which they were submitted.
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SMB
Ubiquinone 0" for the Treatment of Pain
Ubiquinones are prenylated quinones which are wide-spread in the animal and
vegetable kingdoms. They are derivatives of 2,3-dimethoxy-5-methyl-1,4-
benzoquinone having linearly linked isoprene units in the 6-position.
Depending on
the number of isoprene units, the ubiquinones are designated as Q-1, Q-2, Q-3
etc. In most mammals including humans, Q-10 (2,3-dimethoxy-S-methyl-6-deca-
prenyl-1,4-benzoquinone) is prevailing. Ubiquinones serve as electron carriers
in
the respiratory chain, and they participate in the cyclic oxidation and
reduction of
substrates in the citric acid cycle. Ubiquinones Qn represent a precondition
of the
energy supply to all cells. The oxidative stress which arises, inter alia,
from a high
oxygen consumption causes damage to the membranes of mitochondria and cells
which result in acute or degenerative disorders of the nervous system. The
nervous system has a very high energy demand for the signal transduction by
membrane potential build-up, ion-channel control, as well as by neuropeptide
and
neurotransmitter vesicle formation.
Ubiquinone Q-10 (also referred to as coenzyme Q-10) has previously been used
in
the therapy of heart diseases.
Surprisingly, it has now been found that ubiquinone Q~ and ubiquinone Q"
precur-
sors can be used for the treatment of pain. Thus, they can also be used in
methods
for the preparation of agents for the treatment of pain.
The term "ubiquinone Q" precursors" refers to compounds which are converted to
ubiquinone Qn in the body. These include, on the one hand, the
ubihydroquinones,
which are in an equilibrium with the ubiquinones, as well as simple esters of
the
ubihydroquinones with short-chained carboxylic acids having from 1 to 10
carbon
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atoms, for example, acetate, propionate or butyrate esters. These precursors
are
converted to the corresponding ubiquinones after the application thereof.
Ubiquinone Q-10 is preferably used because this is the main ubiquinone in
humans.
According to the invention, there can be treated, in particular, pain caused
by a
disturbance in the stimulus conduction in the nerves, and/or are out of
proportion
with the external cause. This is pain for which either there is no external
cause, or
an excessive signal is produced upon a minor cause and under~oxidative stress
conditions of the nerves.
The substances to be used according to the invention can be preferably
employed
for the treatment of pain which is caused by migraine, dialysis, herpes
zoster,
cancer, diabetic neuropathy, or generalized pain conditions. The treatment can
be
done by administration in oral, parenteral, local, inhalative or intranasal
form. The
kind of administration must be adapted to the .pain condition to be treated.
Thus,
for example, it has been found that migraine can be treated even with high
doses
of Q-10 only with very limited success when oral administration is used.
However,
when used in the form of oral and nasal sprays, small amounts are sufficient
for a
fast and effective elimination of migraine pain. Good results were achieved
already
with doses of about 20 mg.
In the case of herpes zoster, even the local application of Q-10 in the form
of
creams or gels has even proven useful. It is critical that sufficient amounts
of the
ubiquinones or ubiquinone precursors arrive at the place in which the pain
caused
by disturbances of the signal transmission of the nerve system has its origin.
By combination with lung surfactant factor (pulmonary surfactant factor) as
described in WO 08/35660, this effect can even be enhanced.
In kidney dialysis patients, the administration of ubiquinone or its
precursors
before the dialysis causes the dialytic procedure to proceed in a tolerable
way.
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Due to the low dose which is already effective for treating migraine pain, the
ubiquinone Q~ or its precursors are preferably used in the form of a spray,
prefera-
bly a nasal spray, according to the invention.
In principle, the single dose may be as high as 1,000 mg.
Ubiquinones are lipophilic substances which are virtually insoluble in water.
However, a particularly high effectiveness was found when the ubiquinone Qn or
its
precursors are in aqueous dispersion. Aqueous colloidal dispersions are
particularly
preferred. The preparation of the corresponding dispersions is described in WO
95/05164 and in the related DE-A-43 27 063.
