U.S. patent application number 10/041382 was filed with the patent office on 2002-05-16 for treatment of fibromyalgia with ubiquinone 10 and succinic acid.
Invention is credited to Sneed, Paul A..
Application Number | 20020058712 10/041382 |
Document ID | / |
Family ID | 22663761 |
Filed Date | 2002-05-16 |
United States Patent
Application |
20020058712 |
Kind Code |
A1 |
Sneed, Paul A. |
May 16, 2002 |
Treatment of fibromyalgia with ubiquinone 10 and succinic acid
Abstract
A method is described for using a combination of ubiquinone 10
and succinic acid in the treatment of human patients afflicted with
fibromyalgia to alleviate one or more symptoms associated with that
disease state. Fibromyalgia positive patients treated buccally,
sublingually or by oral ingestion administration of ubiquinone 10
and succinic acid enjoy a reduction in clinical symptoms of the
disease.
Inventors: |
Sneed, Paul A.; (Cisco,
TX) |
Correspondence
Address: |
Barnes & Thornburg
11 S. Meridian St.
Indianapolis
IN
46204
US
|
Family ID: |
22663761 |
Appl. No.: |
10/041382 |
Filed: |
January 8, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10041382 |
Jan 8, 2002 |
|
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09780299 |
Feb 9, 2001 |
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60181314 |
Feb 9, 2000 |
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Current U.S.
Class: |
514/678 ;
514/574 |
Current CPC
Class: |
A61K 2300/00 20130101;
A61K 2300/00 20130101; A61K 31/194 20130101; A61K 45/06 20130101;
A61K 31/194 20130101; A61P 21/00 20180101; A61K 31/122 20130101;
A61K 31/122 20130101; A61P 19/04 20180101 |
Class at
Publication: |
514/678 ;
514/574 |
International
Class: |
A61K 031/19; A61K
031/122 |
Claims
What is claimed is:
1. A method for treating a human patient suffering from
fibromyalgia to produce a therapeutic response in said patient,
said method comprising the step of administering to the patient
ubiquinone 10 and succinic acid each at a dose of about 5 to about
500 mg/70 kg patient.
2. The method of claim 1 wherein the ubiquinone 10 and the succinic
acid are each administered at a dose of about 50 to about 400 mg/70
kg patient.
3. The method of claim 1 wherein the ubiquinone 10 and the succinic
acid are each administered at a dose of about 50 to about 200 mg/70
kg patient.
4. The method of claim 1 wherein the ubiquinone 10 and the succinic
acid are formulated in combination in a pharmaceutically acceptable
solid dosage form.
5. The method of claim 1 wherein the ubiquinone 10 and the succinic
acid are formulated in combination in a pharmaceutically acceptable
liquid dosage form.
6. The method of claim 4 wherein the solid dosage form is a
saliva-soluble solid dosage form of said combination which is
administered by being introduced into the mouth of the patient and
held in the mouth for a period of time sufficient to dissolve in
saliva in the patient's mouth to form a saliva solution comprising
ubiquinone 10 and succinic acid.
7. The method of claim 6 wherein the solid dosage form is a
lozenge.
8. The method of claim 1 wherein the ubiquinone 10 and the succinic
acid are administered by oral ingestion.
9. The method of claim 1 wherein the ubiquinone 10 and the succinic
acid are administered bucally.
10. The method of claim 1 wherein the ubiquinone 10 and the
succinic acid are administered sublingually.
11. The method of claim 1 wherein the ubiquinone 10 and the
succinic acid are administered parenterally.
12. The method of claim 1 wherein the dose of ubiquinone 10 and
succinic acid is administered 1 to 4 times a day until the
patient's symptoms of fibromyalgia have subsided.
13. A pharmaceutical composition comprising therapeutically
effective amounts of ubiquinone 10 and succinic acid as the active
ingredients, and a pharmaceutically acceptable carrier
therefor.
14. The pharmaceutical composition of claim 13 in the form of a
liquid solution.
15. The pharmaceutical composition of claim 13 in the form of a
capsule or caplet.
16. The pharmaceutical composition of claim 13 in the form of a
tablet.
17. The pharmaceutical composition of claim 13 in gel-seal
form.
18. The pharmaceutical composition of claim 13 in the form of a
lozenge.
19. The pharmaceutical composition of claim 13 adapted for oral
administration.
20. The pharmaceutical composition of claim 13 adapted for
parenteral administration.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C.
.sctn.119(e) to U.S. Provisional Application No. 60/181,314, filed
Feb. 9, 2000, which is expressly incorporated by reference
herein.
FIELD OF INVENTION
[0002] The present invention relates to a composition and method
for treatment of patients afflicted with fibromyalgia. More
particularly, this invention is directed to a composition and
method for relieving symptoms associated with fibromyalgia in human
patients by administering a combination of ubiquinone 10 and
succinic acid.
BACKGROUND AND SUMMARY OF THE INVENTION
[0003] Fibromyalgia is a common disabling disorder characterized by
chronic musculoskeletal aches and pain, stiffness, general fatigue,
and sleep abnormalities including diminished stage four sleep.
Examination of affected patients reveals increased tenderness at
muscle and tendon insertion sites, known as "tender points."
Fibromyalgia patients experience severe morning stiffness and a
generalized decreased of overall physical function, and they are
often prone to headaches, memory and concentration problems,
dizziness, numbness and tingling, and crampy abdominal or pelvic
pain. Fibromyalgia affects 2-4% of the population and is most
frequently found in women between 20 and 50 years old, although it
can also affect men, the elderly and minors.
[0004] Diagnosis of fibromyalgia is often overlooked due to the
general nature of the symptoms and the lack of diagnostic lab or
x-ray abnormalities. The disorder is often concomitant with, masked
by or confused with other diseases such as rheumatoid arthritis,
chronic fatigue syndrome or irritable bowl syndrome. However,
chronic fatigue syndrome (CFS) can be distinguished from
fibromyalgia because patients with CFS are likely to have symptoms
of viral illnesses such as fever, sore throat, and lymph node pain.
A physician can positively diagnose fibromyalgia syndrome by
finding the symptoms of musculoskeletal pain throughout the body
and pain at more than 11 of 18 symmetrically distributed
characteristic "tender points" when a finger pressure of about 4 kg
is applied to the area, which test is known as the "tender point
index," or when tender points are detected with dolorimetry.
[0005] Currently the best treatment available for fibromyalgia
consists of a combination of analgesics, sleep aids, exercise
programs emphasizing stretching and cardiovascular fitness,
relaxation techniques and other measures to reduce muscle tension,
and educational programs to reduce emotional and physical stress.
Numerous pharmaceutical regimens have been tried including
treatment with serotonin modulators and antisera to endogenous
psychoactive agents. Therapeutic response can be assessed by the
reduction of pain in the tender point index and improvement in
several generalized criteria such as physical function, stiffness,
fatigue, depression, tenseness, etc. Responses to these various
therapies have proven variable within a patient pool and have
rarely exceeded modest relief of some symptoms. Often, initial
therapeutic gains are temporary with the long term outcome
marginally if at all distinguishable from placebo results.
[0006] Ubiquinone 10 and succinic acid are physiological substances
present in all living cells. Succinic acid is oxidized to fumarate
as one of the nine steps in the citric acid cycle, and oxidation of
succinic acid results in the release of two electrons which are
transferred to flavin adenine dinucleotide (FAD) to generate the
reduced form of the molecule, FADH.sub.2. Electrons are then
sequentially transferred between various flavin-linked
dehydrogenases in the electron transport pathway localized on the
inner mitochondrial membrane. Electron transport results in proton
transport across the mitochondrial membrane and powers ATP
synthesis through coupling with the oxidative phosphorylation
pathway.
[0007] Ubiquinone 10 (CoQ10) is a lipophilic electron carrier that
transports electrons between the various flavin-linked
dehydrogenases in the electron transport pathway through reduction
and oxidation of CoQ10. CoQ10 contains ten isoprene units in the
multiprenyl side chain of the molecule which renders CoQ10
lipophilic and facilitates interaction of the molecule with the
inner mitochondrial membrane where the components of the electron
transfer chain are located. CoQ10 complexes with succinic acid and
succinate dehydrogenase, the enzyme responsible for catalyzing the
oxidation of succinic acid to fumarate, and acts as an electron
carrier to facilitate the transfer of electrons from succinic acid
to FAD. CoQ10 is widely distributed in tissues and may also act an
antioxidant for such endogenous molecules as low density
lipoproteins.
[0008] There exists a significant need for more effective therapy
for patients afflicted with fibromyalgia. The present invention is
directed to a method for treating a human patient suffering from
fibromyalgia to produce a therapeutic response in the patient. The
method comprises the step of administering to the patient
ubiquinone 10 and succinic acid each at a dose of about 5 to about
500 mg/70 kg patient. In one embodiment of the invention the
ubiquinone 10 and the succinic acid are each administered at a dose
of about 50 to about 400 mg/70 kg patient and are administered by
oral ingestion, bucally, sublingually, or parenterally. In another
embodiment of the invention the ubiquinone 10 and succinic acid are
each administered at a dose of about 50 to about 200 mg/70 kg
patient. The ubiquinone 10 and succinic acid may be administered in
a solid, liquid, or saliva-soluble dosage form, such as a lozenge.
The daily doses can be divided into multiple doses administered one
or more times per day.
[0009] In another embodiment, the invention provides a
pharmaceutical composition comprising therapeutically effective
amounts of ubiquinone 10 and succinic acid as the active
ingredients, and a pharmaceutically acceptable carrier therefor.
The pharmaceutical composition can be in the form of a liquid
solution, a capsule, a caplet, a tablet, a gel-seal, or a lozenge
and can be adapted for oral or parenteral administration.
DETAILED DESCRIPTION OF THE INVENTION
[0010] The present invention provides a method for treating a human
patient suffering from fibromyalgia to produce a therapeutic
response in the patient. The method comprises the step of
administering to the patient ubiquinone 10 and succinic acid each
at a dose of about 5 to about 500 mg/70 kg patient. The ubiquinone
10 and succinic acid may be administered by oral ingestion,
bucally, sublingually, or parenterally and may be administered in a
pharmaceutically acceptable solid, liquid, or saliva-soluble dosage
form, such as a lozenge. In a preferred embodiment, the ubiquinone
10 and succinic acid are taken with food. In accordance with the
present invention, there is also provided a pharmaceutical
composition comprising therapeutically effective amounts of
ubiquinone 10 and succinic acid as the active ingredients, and a
pharmaceutically acceptable carrier therefor. The pharmaceutical
composition may be in the form of a suspension, a capsule or
caplet, a tablet, a gel-seal, or a lozenge, and may be adapted for
oral or parenteral administration.
[0011] Succinic acid is an intermediate in the citric acid cycle
and, thus, is a physiological compound found in living cells.
Succinic acid is oxidized to form fumarate as a step in the citric
acid cycle and, upon oxidation of succinic acid, two electrons are
released and are transferred to FAD to generate the reduced form of
the molecule, FADH.sub.2, as the first step in the electron
transport pathway. Electrons are then sequentially transferred
between various flavin-linked dehydrogenases in the electron
transport pathway resulting in the generation of ATP through
coupling with oxidative phosphorylation. Ubiquinone 10 is an
electron carrier that facilitates transport of electrons between
the various flavin-linked dehydrogenases in the electron transport
pathway, and complexes with succinic acid and succinate
dehydrogenase to facilitate the transfer of electrons generated by
oxidation of succinic acid to FAD. Methods of producing ubiquinone
10 are well known in the art and one such method is disclosed in
U.S. Pat. No. 4,070,244 incorporated herein by reference in its
entirety. Succinic acid is commercially available from Aldrich
Chemical Company, Milwaukee, Wis.
[0012] In accordance with the present invention, a method is
provided for treating a human patient suffering from fibromyalgia
to produce a therapeutic response. A "therapeutic response" is a
response to treatment with ubiquinone 10 and succinic acid in which
one or more of the clinical symptoms of fibromyalgia in a patient
with the disease are prevented, reduced, or stabilized whether such
improved patient condition is permanent or temporary. Ubiquinone 10
and succinic acid may also be used in combination for the treatment
of other disease states including such diseases as adult onset
diabetes, autoimmune disorders such as lupus erythematosus, and
chronic fatigue syndrome. A "therapeutic response" to treatment
with ubiquinone 10 and succinic acid for any of these disease
states is also a response in which one or more of the clinical
symptoms of disease are prevented, reduced, or stabilized whether
such improved patient condition is permanent or temporary. The term
"succinic acid" as used herein to claim and describe the method and
composition of the present invention will be understood to include
pharmaceutically acceptable salts of succinic acid, succinic acid
anhydride and succinic acid esters which, upon administration to a
patient, can serve as a source of succiniate in vivo via in vivo
hydrolysis or neutralization under physiological conditions.
[0013] In one embodiment of this invention, the method for treating
a patient suffering from fibromyalgia to produce a therapeutic
response comprises the step of administering ubiquinone 10 and
succinic acid by oral ingestion each at a dose of about 5 to about
500 mg/70 kg patient. In another embodiment, the compounds are
administered at a dose of about 50 to about 400 mg/70 kg patient.
In an alternate embodiment, the compounds are administered at a
dose of about 50 to about 200 mg/70 kg patient for relief of one or
more symptoms of fibromyalgia. The daily doses of ubiquinone 10 and
succinic acid can be administered as single daily doses or in more
than one dose per day until the patient's symptoms of fibromyalgia
have subsided. The ubiquinone 10 and succinic acid may also be
administered in different weight ratios in single daily doses or in
a multi-dose regimen, and, preferably, are taken with food. In a
preferred embodiment, for example, the ubiquinone 10 is
administered with food at about 100 mg/70 kg patient per dose and
the succinic acid at about 400 mg/70 kg patient per dose in single
or in two daily doses. In another preferred embodiment, the
ubiquinone 10 is administered at about 25 mg/70 kg patient per dose
and the succinic acid at about 100 mg per dose and the compounds
are taken with food 2-4 times daily with food to achieve daily
ubiquinone 10 and succinic acid doses of 50-100 mg/70 kg patient
and 200-400 mg/70 kg patient, respectively. In yet another
preferred embodiment these same ubiquinone 10 and succinic acid
doses are administered twice daily with food to achieve daily doses
of 50 and 200 mg/70 kg patient, respectively.
[0014] Oral ingestion may be achieved by the use of such dosage
forms of ubiquinone 10 and succinic acid as syrups, sprays, or
other liquid dosage forms, a gel-seal, or a capsule or caplet.
Buccal and sublingual administration comprises contacting the oral
and pharyngeal mucosa of the patient with the dose of ubiquinone 10
and succinic acid either in a pharmaceutically acceptable liquid
dosage form, such as a syrup or a spray, or in a saliva-soluble
dosage form which is held in the patient's mouth to form a saliva
solution of ubiquinone 10 and succinic acid in contact with the
oral and pharyngeal mucosa. Exemplary of saliva-soluble dosage
forms are lozenges, tablets, and the like. Parenteral
administration can be accomplished by injection of a liquid dosage
form of ubiquinone 10 and succinic acid, such as by injection of a
solution of the two compounds dissolved in a pharmaceutically
acceptable buffer. Such parenteral administration may be
intradermal, subcutaneous, intramuscular, intraperitoneal, or
intravenous.
[0015] The ubiquinone 10 and succinic acid intended for buccal or
sublingual administration in accordance with the present invention
is administered to the patient in a dosage form adapted to promote
contact of the administered ubiquinone 10 and succinic acid with
the patient's oral and pharyngeal mucosa. Thus, the dosage form can
be in the form of a liquid solution such as a syrup, spray, or
other liquid dosage form to be administered and used by the patient
in a manner which promotes contact of the ubiquinone 10 and
succinic acid components with oral mucosal tissues, for example, by
holding the ubiquinone 10 and succinic acid solution in the mouth
for up to one or two minutes. Alternatively, the ubiquinone 10 and
succinic acid can be administered by oral ingestion wherein the
compounds are formulated into a syrup to be swallowed by the
patient and not held in the mouth. Syrups for either use may be
flavored or unflavored and may be formulated using a buffered
aqueous solution of ubiquinone 10 and succinic acid as a base with
added caloric or non-caloric sweeteners, flavor oils and
pharmaceutically acceptable surfactant/dispersants. Other liquid
dosage forms, including solutions or sprays containing ubiquinone
10 and succinic acid, can be prepared in a similar manner and can
be administered buccally, sublingually, or by oral ingestion.
[0016] Preferably, the ubiquinone 10 and succinic acid for
buccal/sublingual administration in the present invention is
formulated into a solid dosage form, such as a lozenge or a tablet.
This formulation preferably contains ubiquinone 10, succinic acid
and a saliva-soluble carrier and may optionally contain desirable
excipients, such as buffers, or tableting aids. The solid dosage
form is formulated to dissolve, when held in a patient's mouth, to
form a saliva solution of the ubiquinone 10 and succinic acid to
promote contact of the compounds with the oral and pharyngeal
mucosa.
[0017] In one embodiment, the solid dosage form is in the form of a
lozenge adapted to be dissolved upon contact with saliva in the
mouth, with or without the assistance of chewing, to form a saliva
solution of ubiquinone and succinic acid. In this embodiment,
lozenges are formulated to provide about 5 to about 500 mg/70 kg
patient of ubiquinone 10 and succinic acid, preferably about 50 to
about 400 mg/70 kg patient. In another preferred embodiment, about
50 to about 200 mg/70 kg patient of ubiquinone 10 and succinic acid
is provided upon dissolution of the dosage form in saliva in the
mouth. Ubiquinone 10 and succinic acid are preferably taken with
food.
[0018] Lozenges for use in accordance with this invention can be
prepared, for example, by art-recognized techniques for forming
compressed tablets where the ubiquinone 10 and succinic acid is
dispersed on a compressible solid carrier, optionally combined with
any appropriate tableting aids such as a lubricant (e.g.,
magnesium-stearate) and is compressed into tablets. The solid
carrier component for such tableting formulations can be a
saliva-soluble solid, such as a cold water-soluble starch or a
monosaccharide or disaccharide, so that the lozenge will readily
dissolve in the mouth to release the contained ubiquinone 10 and
succinic acid in saliva solution for contact with and absorption by
the oral/pharyngeal mucosa when the lozenge is held in the mouth.
The pH of the above-described formulations can range from about 4
to about 8.5. Lozenges for use in accordance with the present
invention can also be prepared utilizing other art-recognized solid
unitary dosage formulation techniques.
[0019] Tablets for use in accordance with this invention can be
prepared in a manner similar to that described for preparation of
lozenges or by other art-recognized techniques for forming
compressed tablets such as chewable vitamins. Suitable solid
carrier components for tableting include manitol, microcrystalline
cellulose, carboxymethyl cellulose, and dibasic calcium
phosphate.
[0020] Solid dosage forms for oral ingestion administration include
such dosage forms as caplets, capsules, and gel-seals. Such solid
dosage forms can be prepared using standard tableting protocols and
excipients to provide ubiquinone 10 and succinic acid-containing
capsules, caplets, or gel-seals. Any of the solid dosage forms for
use in accordance with the invention, including lozenges and
tablets, may be in a form adapted for sustained release of the
ubiquinone 10 and succinic acid.
[0021] In accordance with one embodiment of the present invention a
pharmaceutical composition is provided comprising therapeutically
effective amounts of ubiquinone 10 and succinic acid, and a
pharmaceutically acceptable carrier therefor. "Therapeutically
effective amounts" of ubiquinone 10 and succinic acid are amounts
of the compounds which prevent, reduce, or stabilize one or more of
the clinical symptoms of fibromyalgia in a patient suffering from
the disease whether such improved patient condition is permanent or
temporary. In one embodiment the pharmaceutical composition
comprises about 5 to about 500 mg/70 kg patient of ubiquinone 10
and succinic acid per dose in combination with a pharmaceutically
acceptable carrier. A preferred pharmaceutical composition
comprises about 50 to about 400 mg/70 kg patient per dose of each
of the two compounds in combination with the carrier. In another
preferred embodiment, the pharmaceutical composition comprises
about 50 to about 200 mg/70 kg patient of ubiquinone 10 and
succinic acid per dose in combination with the pharmaceutically
acceptable carrier. The ubiquinone 10 and succinic acid may be
present in the pharmaceutical composition at different weight
ratios. Most preferably, the pharmaceutical composition comprises
about 100 mg/70 kg patient per dose of ubiquinone 10 and 400 mg/70
kg patient per dose of succinic acid. In another preferred
embodiment, the pharmaceutical comprises about 25 mg/70 kg patient
per dose of ubiquinone 10 and 100 mg per dose of succinic acid
administered 2-4 times daily with food to achieve daily ubiquinone
10 and succinic acid doses of 50-100 mg/70 kg patient and 200-400
mg/70 kg patient, respectively. In yet another preferred embodiment
the pharmaceutical composition comprises about 50 mg/70 kg patient
per dose of ubiquinone 10 and 200 mg/70 kg patient per dose of
succinic acid administered twice daily with food to achieve daily
doses of 100 and 400 mg/70 kg patient, respectively.
[0022] A "pharmaceutical acceptable carrier" for use in accordance
with the invention is compatible with other reagents in the
pharmaceutical composition and is not deleterious to the patient.
The pharmaceutically acceptable carrier formulations for
pharmaceutical compositions adapted for oral ingestion or
buccal/sublingual administration including lozenges, tablets,
capsules, caplets, gel-seals, and liquid dosage forms, including
syrups, sprays, and other liquid dosage forms, have been described
above. Ubiquinone 10 and succinic acid can also be adapted for
parenteral administration in accordance with this invention using a
pharmaceutical acceptable carrier adapted for use in a liquid dose
form. Thus, ubiquinone 10 and succinic acid can be administered
dissolved in a buffered aqueous solution typically containing a
stabilizing amount (1-5% by weight) of albumin or blood serum. Such
a liquid solution of ubiquinone 10 and succinic acid may be in the
form of a clarified solution or a suspension. Exemplary of a
buffered solution suitable as a carrier of ubiquinone 10 and
succinic acid administered parenterally in accordance with this
invention is phosphate buffered saline prepared as follows:
[0023] A concentrated (20.times.) solution of phosphate buffered
saline (PBS) is prepared by dissolving the following reagents in
sufficient water to make 1,000 ml of solution: sodium chloride, 160
grams; potassium chloride, 4.0 grams; sodium hydrogen phosphate, 23
grams; potassium dihydrogen phosphate, 4.0 grams; and optionally
phenol red powder, 0.4 grams. The solution is sterilized by
autoclaving at 15 pounds of pressure for 15 minutes and is then
diluted with additional water to a single strength concentration
prior to use.
[0024] The daily doses of ubiquinone 10 and succinic acid for
administration in accordance with this invention can be
administered as single doses, or they can be divided and
administered as a multiple-dose daily regimen. Thus, the doses of
ubiquinone 10 and succinic acid may be administered 1 to 4 times a
day until patient symptoms of fibromyalgia have subsided or are
stabilized. Further, a staggered regimen, for example, one to three
days of buccal/sublingual ubiquinone 10 and succinic acid
treatments per week, can be used as an alternative to daily
treatment, and for the purpose of defining this invention such
intermittent or staggered daily regimen is considered to be
equivalent to every day treatment and within the scope of this
invention.
EXAMPLE 1
Preparation Of Ubiquinone 10 And Succinic Acid-Containing Liquid
Solutions
[0025] Ubiquinone 10 is synthesized according to the procedure
described in U.S. Pat. No. 4,070,244 incorporated herein by
reference in its entirety. Succinic acid is purchased from Aldrich
Chemical Company, Milwaukee, Wis. A ubiquinone 10 and succinic
acid-containing liquid solution is prepared by first dissolving
ubiquinone 10 and succinic acid in phosphate-buffered saline. To
prepare a physiological phosphate-buffered saline solution for
dissolution of the ubiquinone 10 and succinic acid, a concentrated
(20.times.) solution of phosphate buffered saline (PBS) is diluted
to obtain a 1.times.solution. The 20.times.PBS solution is prepared
by dissolving the following reagents in sufficient water to make
1,000 ml of solution: sodium chloride, 160 grams; potassium
chloride, 4.0 grams; sodium hydrogen phosphate, 23 grams; potassium
dihydrogen phosphate, 4.0 grams; and optionally phenol red powder,
0.4 grams. The PBS solution is then sterilized by autoclaving at 15
pounds of pressure for 15 minutes and is diluted with additional
sterile water to a 1.times.concentration prior to dissolution of
the ubiqunone 10 and succinic acid. To prepare a dose form for
intravenous administration, ubiquinone 10 and succinic acid are
dissolved in 1.times.PBS at concentrations of 0.5 and 2 mg/ml,
respectively, and the resulting solution (200 ml) is dispensed into
sealable translucent plastic bags for use in intravenous
adminstration of the compounds. These steps are performed under
sterile conditions. Alternatively, ubiquinone 10 and succinic acid
are dissolved in sterile 1.times.PBS at concentrations of 100 and
400 mg/ml, respectively, and 10 ml aliquots are dispensed, under
sterile conditions, into glass vials which are then sealed with a
rubber septum. Such dosage forms are useful for parenteral
administration of the compounds by subcutaneous, intramuscular,
intraperitoneal, and intradermal injection at approximately 1 ml
per dose. The buffered aqueous solution of ubiquinone 10 and
succinic acid is also used as a base for preparing other liquid
formulations of the compounds. For example, a syrup is prepared by
adding art-recognized caloric or non-caloric sweetners, flavor
oils, and pharmaceutically acceptable surfactants/dispersants to an
aqueous solution of ubiquone 10 and succinic acid. Such a syrup
dosage form contains ubiquinone 10 and succinic acid at
concentrations of 100 and 400 mg/ml, respectively, and is
administered in 1 ml amounts. A ubiquinone 10 and succinic
acid-containing spray is similarly formulated, but contains
flavoring in an aqueous form, and a convenient means of delivering
an aerosol spray is utilized.
EXAMPLE 2
Preparation of Ubiquinone 10 And Succinic Acid-Containing
Lozenges
[0026] Lozenges for use in accordance with this invention can be
prepared by art-recognized techniques for forming compressed
tablets. The ubiquinone 10 and succinic acid is dispersed on a
compressible solid carrier and is formed into tablets each
containing a predetermined amount of the active ingredients. For
example, each lozenge may contain 100 mg of ubiquinone 10 and 400
mg of succininc acid, or, alternatively, 25 mg of ubiquinone 10 and
100 mg of succinic acid or any other therapeutically effective
amounts. The solid carrier component for such tableting
formulations can be a saliva-soluble solid, such as a cold
water-soluble starch or a monosaccharide or disaccharide, so that
the lozenge will readily dissolve in the mouth to release the
contained ubiquinone 10 and succinic acid in saliva solution for
contact with and absorption by the oral/pharyngeal mucosa when the
lozenge is held in the mouth. A preferred solid carrier is dibasic
calcium phosphate. The ubiquinone 10 and succinic acid is also
optionally combined with any appropriate tableting aids such as a
lubricant (e.g., magnesium-stearate), a binding agent, a wetting
agent, or a disintegrant. The product is then shaped by
art-recoginized techniques into the desired delivery form. The pH
of the formulations ranges from about 4 to about 8.5.
EXAMPLE 3
Preparation of Ubuquinone 10 And Succinic Acid-Containing
Tablets
[0027] Tablets for use in accordance with this invention can be
prepared in a manner similar to that described in Example 2 for
preparation of lozenges except that a saliva-soluble solid carrier
for dissolution in the mouth is not required. The ubiquinone 10 and
succinic acid may be presented as a powder, and suitable solid
carrier components for tableting include manitol, microcrystalline
cellulose, and carboxymethyl cellulose. A preferred solid carrier
for use in accordance with the invention is dibasic calcium
phosphate. Tablets may also be prepared by other art-recognized
techniques for forming compressed tablets such as chewable
vitamins.
EXAMPLE 4
Treatment Of A Female Fibromyalgia Subject With Ubiquinone 10 And
Succinic Acid Using A Single Daily Dose Regimen
[0028] A 45 year old female subject presents with fatigue,
dizziness, muscle cramps and pain, joint pain, headaches, and
diminished sleep. The subject is examined, and is diagnosed as
suffering from fibromyalgia by finding pain at 14 of 18
characteristic tender points when a finger pressure of about 4 kg
is applied to the area. The subject is treated with ubiquinone 10
and succinic acid-containing lozenges by buccal administration,
with each lozenge containing 25 mg of ubiquinone 10 and 100 mg of
succinic acid, in four daily doses with food for one month. After 1
month of daily treatment with the ubiquinone 10 and succinic
acid-containing lozenges, the subject's condition is improved with
the dizziness, muscle and joint pain, and headaches diminished.
Considerable improvement in physical activity and sleep is also
observed. The subject is reexamined to determine the tender point
index after treatment with ubiquinone 10 and succinic acid and pain
is found at only 4 of the 18 characteristic tender points. The
subject continues on the same treatment regimen and no side effects
are observed.
EXAMPLE 5
Treatment of a Male Fibromyalgia Subject With Ubiquinone 10 And
Succinic Acid
[0029] A 37 year old male subject presents with general fatigue,
restlessness, muscle and joint pain, numbness, and abdominal
cramps. The subject is examined, and is positively diagnosed as
suffering from fibromyalgia by finding pain at 17 of 18
characteristic tender points when 4 kg of finger pressure is
applied. The subject is treated with ubiquinone 10 and succinic
acid by parenteral administration of a ubiquinone 10 and succinic
acid-containing buffered liquid solution. The liquid dose
formulation is administered so that the subject receives a dose of
100 mg per day of ubiquinone 10 and 400 mg per day of succinic acid
with food for 14 days. The subject is reexamined to determine the
subject's tender point index after 14 days and pain is found at
only 6 of the 18 characteristic tender points. Considerable
improvement in the subject's muscle and joint pain and abdominal
pain are observed and the subject indicates that he feels better
physically and mentally. The subject continues treatment on the
same treatment regimen as described in Example 4 and his symptoms
continue to subside. The subject does not complain of any side
effects.
EXAMPLE 6
Treatment of a Female Fibrobyalgia Subject With Ubiquinone 10 And
Succinic Acid Using A Multi-Dose Daily Regimen
[0030] A 29 year old female subject presents with muscle cramps,
joint pain, stiffness, and general fatigue. The subject also
complains of sleep abnormalities. The subject is examined, and is
positively diagnosed as suffering from fibromyalgia by finding pain
at 15 of 18 characteristic tender points when 4 kg of finger
pressure is applied to the area. The subject is treated with
ubiquinone 10 and succinic acid by oral ingestion of a ubiquinone
10 and succinic-containing syrup wherein the subject swallows the
syrup upon administration and does not hold the syrup in the mouth
for a period of time before swallowing. Each dose of this liquid
formulation contains 25 mg of ubiquinone 10 and 100 mg of succinic
acid, and is administered in 4 daily doses with food for a period
of 3 weeks. The subject is reexamined after 3 weeks and pain is
found at only 2 of the 18 characteristic tender points.
Considerable improvement in the subject's muscle and joint pain are
observed and the subject indicates that she feels better
physically. The subject continues on the same treatment regimen and
does not complain of any side effects.
EXAMPLE 7
Treatment of a Female Fibromyalgia Subject With Ubiquinone 10 And
Succinic Acid
[0031] A 48 year old female was positively diagnosed with
fibromyalgia. The subject found no relief for her pain after
receiving standard medical treatment. The subject began treatment
with 50 mg of ubiquinone 10 and 200 mg of succinic acid in capsule
form twice daily with food. The subject experienced dramatic relief
of her symptoms by the fifth day after treatment commenced with
almost complete cessation of symptoms by the fourteenth day after
treatment began. She improved further over a six week period until
she became asymptomatic, and continues on the same treatment
regimen.
EXAMPLE 8
Treatment of a Female Fibromyalgia Subject With Ubiquinone 10 And
Succinic Acid
[0032] A 40 year old female was diagnosed with fibromyalgia and
began treatment with 100 mg of ubiquinone 10 and 400 mg of succinic
acid in a single daily dose in capsule form with food. The subject
experienced some stomach upset with 400 mg of succinic and her
succinic acid dose was reduced to 200 mg per day. The subject
experienced dramatic relief from her pain and other symptoms and
became asymptomatic within 30 days. She continues on the same
treatment regimen with no recurrence of symptoms.
EXAMPLE 9
Treatment Of a Female Fibromyalgia Subject With Ubiquionone 10 And
Succinic Acid
[0033] A 32 year old patient was diagnosed with fibromyalgia and
began treatment with ubiquinone 10 and succinic acid three months
later. The subject was treated with 100 mg of ubiqinone 10 and 200
mg of succinic acid twice daily in capsule form with food. The
subject noted some relief from her symptoms by the end of the first
week of treatment. She continued to improve and complete cessation
of symptoms was observed by the end of thirty days. She continues
on the same treatment regimen and has no reoccurence of
symptoms.
EXAMPLE 10
Treatment of a Female Lupus Erythematosus Subject With Ubiquinone
10 And Succinic Acid
[0034] A 60 year old female diagnosed with lupus found no
satisfactory results with standard medical treatment. The subject
began treatment with 100 mg of ubiquinone 10 and 400 mg of succinic
acid in capsule form with food in two daily doses. The subject
experienced remission of her symptoms within about two weeks after
treatment began and continues on the same treatment regimen.
EXAMPLE 11
Treatment of a Female Lupus Erythematosus Subject With Ubiquinone
10 And Succinic Acid
[0035] A 65 year old female was diagnosed with lupus erythematosus
and was treated using the same regimen as described in Example 10.
The subject experienced complete remission of symptoms in about 2
weeks, and continues on the same treatment regimen.
EXAMPLE 12
Treatment of a Female Subject With Chronic Fatigue Syndrome With
Ubiquinone 10 And Succinic Acid
[0036] A 40 year old female subject was diagnosed with chronic
fatigue syndrome and was sent to numerous specialists without
improvement. The subject began treatment with 100 mg of ubiquinone
10 and 400 mg of succinic acid in capsule form with food once
daily. The subject's symptoms subsided within 3 days and she was
asymptomatic within two weeks, and continues on the same treatment
regimen without recurrence of symptoms.
EXAMPLE 13
Treatment of a Male Diabetes Subject With Ubiquinone 10 And
Succinic Acid
[0037] A 62 year old male subject was diagnosed with diabetes and
had high blood sugar levels even with medical treatment. The
subject began treatment with 50 mg of ubiquinone 10 and 200 mg of
succinic acid in capsule form twice daily with food. The subject's
blood sugar level was lowered to 112 and has been maintained at
that level since the ubiquinone 10 and succinic acid treatment was
initiated. The subject continues on the same treatment regimen.
EXAMPLE 14
Treatment Of A Male Diabetes Subject With Ubiquinone 10 And
Succinic Acid
[0038] A 60 year old male subject was diagnosed with diabetes and
had high blood sugar levels even with medical treatment. The
subject began treatment with 50 mg of ubiquinone 10 and 200 mg of
succinic acid in capsule form twice daily with food. The subject's
blood sugar level was lowered and swelling in his feet subsided.
The subject continues on the same treatment regimen.
EXAMPLE 15
Treatment of a Male Diabetes Subject With Ubiquinone 10 And
Succinic Acid
[0039] A 70 year old male subject was diagnosed with diabetes. He
began treatment with 100 mg of ubiquinone 10 and 400 mg of succinic
acid with food in a single daily dose in capsule form. The
treatment with ubiquinone 10 and succinic acid has lowered and
controlled the subject's blood glucose level and he continues on
the same treatment regimen.
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