Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Using bacteria
Reexamination Certificate
2001-01-09
2004-10-19
Lankford, Jr., Leon B. (Department: 1651)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Using bacteria
C435S171000, C435S071100, C514S008100, C514S168000, C424S234100, C424S725000
Reexamination Certificate
active
06806069
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to ubiquinone compositions that can be used to deliver ubiquinones to a host and to methods of making such compositions.
Ubiquinones, such as Coenzyme Q
10
(hereinafter “CoQ
10
”), are essentially a vitamin-like substance. CoQ
10
is found in small amounts in a wide variety of foods and is synthesized in all tissues. The biosynthesis of CoQ
10
from the amino acid tyrosine is a multi-stage process requiring eight vitamins and several trace elements. Co-enzymes are co-factors upon which comparatively large and complex enzymes depend for their function. CoQ
10
is the co-enzyme for at least three mitochondrial enzymes (complexes I, II and III) as well as enzymes in other parts of the cell.
Mitochondrial enzymes of the oxidative phosphorylation pathway are essential for the production of adenosine triphosphate (ATP), upon which all cellular functions depend. CoQ
10
plays a critical role in the sequential transfer of electrons in the mitochondrion.
In addition to electron transport in the mitochondrion, CoQ
10
has also been found to be important in the prevention of cellular-free radical damage, oxygenation at the cellular level, as well as other benefits.
Studies have demonstrated that sufficient levels of CoQ
10
promote optimal cell function in the human body. Significantly decreased levels of CoQ
10
have been noted in a wide variety of diseases in both animal and human studies. CoQ
10
deficiency may be caused by insufficient dietary CoQ
10
, impairment in CoQ
10
biosynthesis, excessive utilization of CoQ
10
by the body, or any combination.
Various CoQ
10
formulations and methods of administration have been evaluated in clinical settings and demonstrate the potential and versatility of CoQ
10
compositions for a broad spectrum of disorders. CoQ
10
has been labeled a “breakthrough” drug in congestive heart failure—showing clinical benefit in 75% of
Drugs Exp. Clin. Res.,
11: 557-76 (1985)). CoQ
10
has been used to combat the effects of muscular dystrophy, producing clinical benefit in a subpopulation of patients with Duchenne form (Folkers, et al.,
Proc. Natl. Acad. Sci. U.S.A.,
82: 4513-6 (1985)). CoQ
10
has been successfully utilized to battle periodontal disease (Wilkinson, et al.,
Res. Commun. Chem. Pathol. Pharmacol.,
14: 715-9 (1976)). CoQ
10
has been implicated in the reduction in toxicity of chemotherapeutic drugs, e.g., cardiac toxicity of adriamycin (R. Ogura, et al.,
J. Nutr. Sci. Vitaminol.,
28: 329-34 (1982)). CoQ
10
has been successfully implemented in the correction of drug-induced deficiencies, e.g., psychotherapeutic, diabetes and beta-blocker drugs (Katsumoto and Inoue,
Jpn. Circ. J.,
47: 356-62 (1983)). CoQ
10
has been used in immune restoration, e.g., aging, AIDS, allergies (Suzuki, et al.,
Jpn. J. Surg.,
16: 152-5 (1986); Folkers, et al.,
Res. Commun. Chem. Pathol. Pharmacol.,
38: 335-8 (1982); Folkers, et al.,
Biochem. Biophys. Res. Commun.,
193: 88-92 (1993)).
CoQ
10
supplementation can be beneficial at any age, but due to statin-types of hyperlipidimia medications removing naturally occurring CoQ
10
from the body and the age related depletion of the body's natural resources of CoQ
10
by age 35, CoQ
10
supplementation may be most beneficial to those above age 35. Studies have shown that a decrease in CoQ
10
levels by 25% results in an inability of the body to produce enough cellular energy to remain healthy. A decline of 75% in CoQ
10
can be fatal.
Ubiquinones, including CoQ
10
, are essentially insoluble in aqueous media. This insolubility may be attributed to the long hydrocarbon isoprenoid side chain which provides the molecule with its extremely lipophilic characteristics. These characteristics, among other effects, appear to be the source of the very slow absorption rates of the molecule. Pharmacokinetic data has demonstrated that intestinal absorption of ubiquinones is slow and ineffective in human subjects. By way of example, after administration of CoQ
10
there is a lag time of about 1 hour before increased plasma levels of CoQ
10
can be detected. A second absorption peak appears after about 24 hours. Approximately seven days of administration is required to achieve maximum steady-state plasma levels. Furthermore, absorption of orally administered CoQ
10
is variable and generally in the range of only about 2-5%.
Others have primarily focused on the production of the fatty emulsion of CoQ
10
in order to increase bioavailability and stability of CoQ
10
. All of these formulations contain emulsifying agents. In fact, none of these CoQ
10
formulations are free of detergents or surfactants. Further, because of the nature of the oil emulsion, these formulations provide limited bioavailability in concentrations of CoQ
10
to the desired delivery sites in the body. Generally, oil formulations are highly viscous formulations with relatively low CoQ
10
concentration and accumulates slowly into cell membranes; commonly no more than 10 mg per ml. More importantly, emulsions are slowly absorbed and accumulate at low levels in cells.
Therefore, there remains a need for ubiquinone-containing compositions, for example compositions containing CoQ
10
, with improved stability and bioactivity characteristics.
SUMMARY OF THE INVENTION
In accordance with the present invention, an ubiquinone composition is provided. The composition includes a glycoprotein matrix bound to the ubiquinone. In a preferred embodiment, the ubiquinone is CoQ
10
. The glycoprotein matrix can be produced by microorganisms, such as yeast or bacteria. Preferred microorganisms are
Saccharomyces cervisiae
and bacteria within the genus Lactobacillus. The composition of the invention can also include stabilizers or additives to improve its properties. For example, in a preferred embodiment, the composition of the invention also includes a bioflavanoid, such as hesperidin, as a stabilizer.
A nutritional supplement is also provided. As discussed above, ubiquinones, such as CoQ
10
, have been shown to be beneficial for health. The nutritional supplement includes the ubiquinone composition of the invention, having a glycoprotein matrix bound to the ubiquinone.
A method is also provided for preparing an ubiquinone-containing composition. The method includes binding at least one ubiquinone to a glycoprotein matrix. In a preferred embodiment, the glycoprotein matrix is formed by glycoprotein producing microorganisms. Thus, the binding includes contacting the ubiquinone with a glycoprotein producing microorganism under conditions such that the microorganism will produce glycoprotein.
The ubiquinone composition of the invention demonstrates improved properties as compared to commercially available ubiquinone compounds. Thus, a method is also provided for increasing the bioactivity of ubiquinone. A separate method is similarly provided for increasing the stability of ubiquinone. Both methods include binding the ubiquinone, such as CoQ
10
, to a glycoprotein matrix.
A method is also provided for delivering an ubiquinone compound to a host. The method includes binding the ubiquinone with a glycoprotein matrix to form an ubiquinone-containing composition and administering the composition to the host.
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Davis Ruth A.
Hoffmann & Baron , LLP
Lankford , Jr. Leon B.
Pharmachem Laboratories, Inc.
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