Title: Method for the
accelerated in vivo removal of ethanol
United States Patent: 7,323,452
Issued: January 29, 2008
Inventors: Bowen, Jr.; Ward
B. (Brockport, NY), Daniel; Daniel S. (Rochester, NY)
Assignee: Wardan, L.L.C.
Appl. No.: 11/017,387
Filed: December 20, 2004
Pharm Bus Intell
& Healthcare Studies
A method for accelerating the process of
removing ethanol from the blood through the use of certain additives that
accelerate the metabolic oxidation of ethanol, and others which in
addition act as catalysts or "pseudo" enzymes for the oxidation. These
additives include multivalent transition metal ions, as well as complexes
thereof, and NAD.sup.+ which enhance the oxidation reaction. The method
described can act as a sobriety inducer and/or as an effective palliative
for the unpleasant effects of overuse of ethanol.
Description of the
FIELD OF INVENTION
This invention relates to compositions and processes which accelerate the
oxidation of alcohol in human blood. More particularly, the invention
provides for the enhanced in vivo oxidation of ethanol and/or methanol.
BACKGROUND OF THE INVENTION
Alcohol consumption and its consequences have long been a challenge to the
statutes that govern our society. High levels of ethanol in the blood have
far reaching consequences to the user and society, as indicated by 16000
highway deaths and 1.6 million drinking related arrests per year in the
Therefore there is a need to provide a remedy which can be administered to
accelerate removal of alcohol from an individual's bloodstream and
therefore to shorten the period during which the individual is impaired.
There is also a need to provide a remedy to an individual who is affected
by alcohol to such a degree that medical intervention is required.
The source of oxygen, both mechanical and chemical (including the use of
catalase in combination with hydrogen peroxide) is an essential part of
the process, both these enzymes are not oxygen dependent but rather use
NAD.sup.+ as the oxidizing agent.
Even though the combination can include other enzymes, which regenerate
NADH to NAD.sup.+, using glycerol dehydrogenase/dihydroxyacetone, in the
presence of a liberal supply of oxygen is an essential part of the method.
SUMMARY OF THE INVENTION
Formally, the oxidation of ethanol to acetaldehyde and then to acetic acid
can be generically represented by the reactions:
It is therefore the object of this invention to accelerate the rates of
the forward reactions in the equilibria 1 and 2, by introducing additives
which catalyze the forward reactions or which remove product from the
right hand side of the equilibria 1 and 2 to favor their shifting to the
Various additives provide a remedy through an effective and rapid
reduction of the alcohol level in blood of the consumer at a reasonably
short time, in essence a sobriety agent. Such remedy can take the form of
a liquid, a pill, a capsule, a patch or a nasal spray or any other method
known to medical science and any combination thereof. Such remedy can be
self-administered or, in the same or different formulation be administered
at a health care facility where it can be applied intravenously,
intraperitoneally or in any other method know in medical practice. The
product shall apply to all alcohol containing beverages including but not
limited to all beers, wines and hard liquors now in use.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention relates to compositions which when administered to a
person enhance the in vivo physiological process of removing oxidizing
alcohol and particularly from the blood. In this disclosure, the term
"alcohol" when used without qualification is understood to refer to
ethanol. However, certain embodiments of the invention as noted will also
be applicable to methanol.
As alcohol enters the blood stream, the liver begins the process of
detoxification through the production of the enzyme Alcohol Dehydrogenase,
ADH, which catalyzes the oxidation by Nicotinamide Adenine Dinucleotide,
NAD.sup.+, of ethanol to acetaldehyde and Dihydronicotinamide Adenine
Dinucleotide, NADH as shown -- see Original Patent.
The equilibrium constant of this reaction
is 1, indicating that it is rather inefficient, allowing sufficient
amounts of alcohol to remain in the blood and to cross the blood-brain
barrier. It is the purpose of this invention to find ways of increasing
the efficacy or accelerating this reaction.
In one embodiment of this invention, accelerated oxidation is accomplished
by introducing a chemical accelerator of the ADH enzyme, driving the
reaction toward acetaldehyde. Such accelerators include, zinc ions (as ADH
is a Zinc Enzyme), pyridoxamine or pyridoxamine phosphate (formulae 1a and
1b, see Original
Patent) or a combination thereof .
It is a particular advantage in the case of one of the above accelerators
(zinc) that it is an essential element or a part of the Vitamin B6 system
In another embodiment of this invention, the reversible reaction above can
be shifted toward irreversibility by the removal of one or more of the
products (Le Chatelier's Principle). This is accomplished through the
introduction of a reactive agent that reacts with acetaldehyde, thus
removing it from the equilibrium and driving the reaction forward. Such an
agent includes pyridoxamine or pyridoxamine phosphate (formulae 1a and 1b, see Original
Patent) or the basic amino acids lysine (formula 2, see Original
Patent) and arginine (formula 3, see Original
Patent). A solubilized form of "Purpald" (formula 4, see Original
Patent) may also be useful. Other agents reactive with acetaldehyde
include thiamine. A sufficient quantity of the reactive agent is
administered to provide an in vivo concentration of the reactive agent at
least chemically equivalent to an amount of acetaldehyde resulting from
Lysine and arginine are essential amino acids, so their introduction would
not cause an undue risk to the user. Further, being basic, these amino
acids can help neutralize the acid formed during the oxidation, thus
further shifting the equilibrium toward product. In the presence of a
base, the acetic acid produced by equilibrium (2) is neutralized, which
pulls the reaction to the right. This consumes acetaldehyde from
equilibrium (1), which is thus pulled to the right and consumes more
Any base can be used provided that it is not harmful to the body. For
example, the base can be sodium carbonate, sodium bicarbonate, trisodium
phosphate, disodium hydrogen phosphate or tris (hydroxymethyl)-aminomethane.
A sufficient quantity of the base is administered to provide an in vivo
concentration of the base at least chemically equivalent to the acid
resulting from the oxidation of the ethanol.
The removal of acetaldehyde can also be accomplished by its enzymatic
oxidation to acetic acid as shown below in Equation (3) -- see Original
In one embodiment of the invention this
can be accomplished by adding acetaldehyde dehydrogenase or an accelerator
thereof or a combination of the two. When in vivo, the dehydrogenase
should be present in an amount at least chemically equivalent to the
amount of blood alcohol or, more precisely to acetaldehyde, the oxidation
product of alcohol. This translates to a concentration in the range 0.1-10
Optionally the dehydrogenase may be stabilized with zinc ions since the
dehydrogenase might otherwise degrade. Preferably, the concentration of
zinc ions is at least 1% of the molar concentration of the dehydrogenase.
By increasing the amount of one of the reactants, the equilibrium can be
shifted toward product. Thus, a formulation containing NAD.sup.+ can be
useful. A sufficient quantity of NAD.sup.+ is administered to provide an
in vivo concentration of NAD.sup.+ in the range of 0.05% to 5% of the
maximum expected in vivo molar concentration of ethanol.
Any combination of the above may also be beneficial. Thus, a formulation
containing acetaldehyde dehydrogenase, NAD.sup.+, pyridoxamine phosphate
and zinc arginate or lysinate (or both) can be useful.
In another embodiment of the invention, the acetaldehyde can be chemically
or enzymatically converted to an innocuous derivative, which can later be
removed from the body. These derivatives include, but are not limited to,
esters, ethers, acetals, ketals and urethanes.
Under proper aerobic conditions and with sufficient acid neutralizing
agents, the aerobic oxidation of alcohol to acetic acid catalyzed by
Alcohol Oxidase, AO, is as shown -- see Original
This may also be useful, particularly in
combination with any of the above schemes.
In another embodiment of the invention, the acetic acid formed in either
the acetaldehyde dehydrogenase or the alcohol oxidase reaction, or the
combination of the two, can be converted to methane and carbon dioxide
through a methanogenetic enzyme, thus driving the alcohol oxidation
further toward irreversibility, as shown in equation (4) below:
In another embodiment of this invention, the enzymatic reaction can be
accelerated by a charge-transfer agent such as thiamine, (formula 5),
retinoic acid (formula 6), an isoflavonoid or a pyranoside thereof (e.g.
daidezin (formula 7) or its 7-glucoside, commonly known as aloin, (formula
8)), and 4,5-Dihydro-4,5-dioxo-1H-pyrrolo [2,3-f]
quinoline-2,7,9-tricarboxylic acid, also known as either
pyrroloquinolinequinone (PQQ) or methoxatin (formula 9), or any
combination thereof, lipoic acid, retinoic acid, retinal, retinol, and
derivatives and analogs thereof. A sufficient quantity of the
charge-transfer agent is administered to provide an in vivo concentration
of the charge-transfer agent in the range from 0.1% and 2% of the maximum
expected in vivo molar concentration of ethanol.
In a further embodiment of the invention, various accelerants can be used
to supply energy to the forward reactions of equilibria 5 and 6. Such
accelerants include adenosine 5'-triphosphate, adenine-9-.beta.-D-arabinofurasnoside
5'-trophosphate 2'-deoxadenosine 5'-triphosphate, and
2',3'-dideoxyadenosine 5'-triphosphate. They also include carbohydrates
such as fructose, arabinose, ribose, deoxyribose, and their phosphorylated
derivatives. A sufficient quantity of the accelerant is administered to
provide an in vivo concentration in the range from 1% to 100% of the
maximum expected in vivo molar concentration of ethanol.
In another embodiment of this invention, a combination of some or all of
the above with substances that prevent or delay the absorption of gastric
alcohol into the blood is also envisaged. Such substances include
unsaturated fatty acids, dietary fiber, and surfactants such as oleic
acid, lecithin, the plant surfactant saponin and taurine, (formula 10, see Original
The concentration of the surfactant in the composition should be in the
range 0.02% and 0.2% by volume.
Some surfactants which also act as charge transfer agents can be used.
These include lipoic acid, retinoic acid, retinal, retinol, and
derivatives and analogs thereof. The concentration of the combined
surfactant and charge-transfer agent should be between 0.1% and 2% of the
maximum molar concentration of ethanol. A sufficient quantity of the
combined surfactant and charge-transfer agent is administered to provide
an in vivo concentration of the surfactant and charge-transfer agent
between 0.1% and 2% of the maximum expected molar concentration of
In yet another embodiment of this invention, the acceleration is effected
by multivalent transition metal ions and their derivatives capable of
acting as a pseudo enzyme in a dehydrogenase reaction. The ions include,
but are not limited to, ions of elements of Groups IVa through VIII of the
Periodic Table and their complexes or any combination thereof.
Preferred sources of such ions include: vanadyl sulfate; potassium
ferricyanide, ammonium iron (III) citrate, ammonium molybdate, ammonium
phosphomolybdate, sodium tungstate, and sodium phosphotungstate. Other
sources include ammonium manganese (III) sulfate, zirconium (IV) EDTA,
niobium (IV) EDTA, tetratkis (tropolinato) niobium (V) chloride, tetratkis
(tropolinato)tantalum (V) chloride, cobalt (III) hexammine chloride, and
chromium (III) picolinate. A sufficient amount of transition metal ion
administered to provide an in vivo concentration of the ion in the range
0.05% to 2% of the maximum expected in vivo molar concentration of
In the foregoing disclosure some reactions, such as those involving the
enzyme ADH, are specific to ethanol, while others may apply also to
methanol. In general, the multivalent transition metal ions and their
complexes mentioned above would be expected to oxidize methanol and
ethanol alike, via reactions which may sometimes involve NAD.sup.+. It has
been found in particular that vanadyl sulfate/NAD.sup.+ is effective in
oxidizing methanol. This invention therefore encompasses the in vivo
oxidation of both ethanol and methanol in the blood.
Optionally, any of the embodiments can also include dietary constituents
such as dietary fiber, garlic oil and onion oil, or medications including
such commonly available pain relieving ingredients as aspirin, ibuprofen
Claim 1 of 71 Claims
1. A process for accelerating
in vivo oxidation of alcohol, comprising the steps of: (a) preparing a
composition comprising NAD+ and a catalyst comprising at least one of a
species selected from the group consisting of a multivalent transition metal
ion and a complex thereof, excluding manganese, iron, chromium, copper and
zinc; the species being in a state selected to accelerate in vivo oxidation
of alcohol in the absence of a dehydrogenase where said catalyst effects the
oxidation of NADH, thus recycling NAD+, and the composition having a
sufficient quantity of the transition metal ion to provide an in vivo
concentration of the ion in the range of 0.05% to 2% of a maximum in vivo
molar concentration of ethanol; and (b) administering the composition in
vivo to a subject in need of accelerated removal of alcohol from the
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