CA1336681C - Composition for partially counteracting the effect of alcohol - Google Patents

Abstract

The present invention relates to compositions useful for counteracting the effect of certain toxic chemicals and in particular improving the body's rate of removing the toxic chemicals. In particular, the present invention provides for a composition comprised of one or more defence substances which increase the body's natural toxic chemical defences in combination with one or more additives and nutrients which are generally depleted as a result of alcohol consumption.
Such additives and nutrients are selected from the group consisting of amino acids, vitamins, lipids and other nutrients such as electrolyte replacing compounds. An activated liver composition prepared by a novel alkaline extraction process, various glucuronic acid, cicloxillic acid and thioctic acid derivatives, silymarin group compounds or citiolone are utilized as the defence substances which increase the body's natural toxic chemical defences.

Description

Ct~POSITION FOR Pl~RTIAt.T.Y CGUN ~ A~TING TPF FF'FF~CT OF
AT COPOT-F TF.T-T ) OF TPF. TNVF~NT TON

The present invention relates to compositions useful for partially counteracting the effect of certain toxic chemicals, including in particular, alcohol.

P~CKC.`Rt)t7Nr) OF TPF~ INVF~NTION

It has long been appreciated that the use (and particularly the abuse) of alcohol results in extensive costs (both financial and otherwise), to the individual involved, to his family and friends and to society in general. It has also been appreciated that a viable and effective method to counteract the effects of alcohol would be desirable.

To date, the products available for such applications have been limited to alcohol sensitizing drugs used for enforcing sobriety in alcoholism diseased patients. Examples of such drugs are disulfiram and calcium carbamide. Such drugs are usually administered only to persons who habitually abuse alcohol, in conjunction with other therapeutic methods, specifically psycho-social and behavioural interventions.

The a^tion of such drugs has been postulated to be due to inhibition of aldehyde dehydrogenase, thus blocking the oxidation of alcohol at the acetaldehyde stage. The combination of the build up of acetaldehyde and the various ~etabolites of the drugs, results in numerous negative side effects observed when alcohol is administered to someone on such medication.

_~ 2 - t 33668 1 , .
SIJM~RY OF T~F. INVF~l~TION

The present invention provides for a composition for improving the body's rate of removing certain toxic chemicals, including in particular, alcohol. The composition is comprised of one or more substances which increase the body's natural toxic chemical defences either alone or, in certain cases, in combination with additives and various nutrients which are generally depleted as a result of alcohol consumption.

In another aspect of the invention, an activated liver composition is utilized as a substance which increases the body's natural toxic chemical defences. In yet another aspect of the invention, a novel process for preparing the activated liver composition is provided.

In yet another aspect of the invention, various glucuronic acid, cicloxillic acid and thioctic acid derivatives, citiolone and silymarin group compounds are utilized as substances which increase the body's natural toxic chemical defences.

In yet another aspect of the invention, the various additives which are added to the composition are one or more additives selected from the group consisting of amino acids, vitamins, lipids, including fatty acids and phospholipids, analgesies and other nutrients such as electrolyte replacing compounds.

The composition of the present invention is useful for counteracting, at least partially, the effect of alcohol and certain other toxic compounds (such as certain opiate derivatives and other alkaloids) in mammals, such as humans. It is believed that the composition of the invention may act either 3 ~ 1 33668 1 .

by decreasing the absorption of alcohol by the body or by increasing the metabolism of alcohol ln the body.

In yet another aspect of the invention, a method for improving the body's rate of removing consumed alcohol comprising administering the compositions of the present invention is provided.

DF~TATT.F.n DF~.~CRTF'TION OF T~ INVF.NTION

The composition of the present invention comprises one or more substances which increase the body's natural toxic chemical defences either alone or, in certain cases; in combination with additives and various nutrients which are normally depleted with or during alcohol consumption. The additives and nutrients are one or more additives selected from the group consisting of amino acids, vitamins, lipids, including fatty acids and phospholipids, analgesies and other essential nutrients. These additives can be in the form of the base compounds or any of their common derivatives.

Such substances (hereinafter referred to as "defense substances") which increase the body's natural toxic chemical defences are substances which generally will remove or aid the liver in removing the toxic chemical from the body. Thus, such defence substances can include enzyme preparations which will aid in the metabolism of the toxic chemical or complexing or conjugating agents which will complex or bind the toxic chemical and its metabolites and aid in its clearance from the body.

".
--~ Such defence substances include an activated,liver composition containing a heavy metal compound preferably prepared in accordance with the process described herebelow, glucuronic acid and its derivatives, such as glucuronamide or glucuronolactone, thioctic acid and its derivatives, cicloxillic acid and its derivatives, citiolone and silymarin group compounds, in particular, silybin.

It is postulated that the activated liver composition provides enzymes which aid in the metabolism of the toxic chemicals, for instance alcohol dehydrogenase to metabollze alcohol. The other defence substances such as glucuronic acid and its derivatives, thioctic acid and its derivatives, cicloxillic acid and its derivatives, citiolone and silymarin group compounds are postulated to act as complexing or conjugating agents which will complex or bind the toxic chemical and its metabolites and aid in its clearance from the body.

Experimental results suggest that, when more than one of such defence substances are present in the composition, they may unexpectedly act in synergy to increase the body's natural toxic chemical defences. Such combinations of defence substances include the activated liver composition in combination with one of the conjugating or complexing agents such as glucuronic acid and its derivatives, thioctic acid and its derivatives, cicloxillic acid and its derivatives, citiolone and silymarin group compounds. In addition, preliminary tests suggest that two or more glucuronic acid derivatives, such as glucuronamide or glucuronolactone, also demonstrate possible synergism.

Furthermore, it is believed that each of such defence substances may have different kinetic characteristics, such as, the time of onset and duration of activity in the body.
Accordingly, combining different defence substances would appear to allow control over the timing of the period during which the composition is effective. This may allow a user to ingest (or otherwise administer) the composition prior to the time at which he expects to ingest alcohol. Alternatively, a different ~ 5 - 1 33668 1 composition may allow the user to ingest ~or otherwise administer) the composition for rapid, immediate effect, say during or after alcohol ingestion.

Addition of nutrients to the composition also aids, to an unexpected degree, the counteracting of the effect of the toxic substance. It is believed that such addition relieves the taxing of the liver caused by depletion of the nutrients as a result of the intake of the toxic substance and allows the composition to be unexpectedly effective.

The term "derivative" in this specification means any of the common derivatives of a base compound which have the same activity as the base compound and are non-toxic in the ranges employed. Thus, for example, where the base compound is an acid, its derivatives include pharmaceutically acceptable salts, esters, amides and lactones of such acids. Such salts include salts formed from non-toxic bases as, for example, the salt with an inorganic base, such as a sodium salt, a potassium salt, etc.
and the salt with an organic base, such as an ammonium salt, an alkylamine salt, etc. Such esters include esters formed from aliphatic or aromatic groups, such as straight or branched chain alkyl groups having 1 to 6 carbon atoms, cycloalkyl groups having 3 to 8 carbon atoms, and aryl groups such as phenyl or benzyl. Such groups may be unsubstituted or substituted with substituents such as halo, amino, alkyl, among others. Such amides include unsubstituted amides and amides substituted with such substituents as alkyl, cycloalkyl, and aryl groups which themselves may be substituted by the above substituents.

The lmino acids which can be included in the compositions are any of the amino acids which either occur naturally in the body or are commonly administered as dietary or therapeutic supplements. Preferable amino acids include glutamate, alanine, _ 6 ~ 1 33668 1 glyclne, choline (and its derivatives), inositol, serine, cysteine, histidine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine and valine. In particular, it has been demonstrated that blood concentrations of certain amino acids can become depressed with alcohol intake, "Alcohol and the Cell", ANN . OF T~F, NY A~An~Y OF SCI~ , Ed.
Emanuel Rubin; Vol. 492, 1987. Those latter amino acids may also be included into a formulation in order to restore the natural balance of the amino acid composition within in the body. Furthermore, the blood levels of amino acids may differ between habitual alcohol users and those who do not use alcohol regularly. It may therefore also be preferred to administer a balanced amino acid composition to counter the effects of alcohol intake in alcoholic and non-alcoholic patients. The amount of any of the amino acids added to the composition can be any amount up to and including the amount recommended as the m~x; mllm daily allowance by any of the health regulatory agencies such as the Food and Drug Administration in the United States.

The vitamins which can be included in the compositions include Vitamin Bl, Vitamin B2, Vitamin B6, nicotinamide, folic acid, Vitamin B12 and ascorbic acid. The amount of any of the vitamins added to the composition can be any amount up to and including the amount recommended as the m~x;mllm daily allowance by any of the health regulatory agencies such as the Food and Drug Administration in the United States.

The lipids which can be included in the compositions include phospholipids such as glycerophosphates, glyceryl-phosphorylcholine, lysophospholipids, lysophosphatidylcholines, phosphatidic acids, dimyristoylphosphatidylcholine, 1,2-dipalmitoylphosphatidylcholine, phosphatidylglycerols, phosphoinositides, phosphatidylcholine, phosphatldylethanolamine, cardiolipin, phosphatidylserine and 7 ^ 1 33668 1 phosphatidylinositol, as well as fatty acids such as linoleic acid and oleic acid.

It is preferred to add the lipid preparation to the composition as a premix of such lipids. A preferred such premix contains phosphatidylcholine, phosphatidylethanolamine, cardiolipin, phosphatidylserine, phosphatidylinositol, linoleic acid, and oleic acid. Most preferably, the premix contains the liplds in the following proportions phosphatidylcholine appr 15.0%, phosphatidylethanolamine appr 10.5%, cardiolipin appr

2.4%, phosphatidylserine plus phosphatidylinositol appr 2.1%, linoleic and oleic acids (50:50) appr 70.0%.

The essential nutrients which can be included in the compositions include electrolyte replacing compounds which aid ......
in replacement of electrolytes lost by the body, such as sodium and potassium salts. Such sodium and potassium salts include potassium chloride, sodium chloride, and sodium bicarbonate among others. The amount of any of these nutrients included in the composition can preferably be any amount up to and including the amount required for complete replacement of such essential nutrients.

It may also be desirable to include in the composition other additives such as analgesics, as for example, acetaminophen or acetylsalicylic acid, or central nervous system stimulants, as for example, caffeine and its salts.

Administration of the compositions of the present invention can be via any of the accepted modes of administration, such as oral or parenteral, and will depend upon the use for which the composition is intended.

_ 8 - 1 33668 1 Depending upon the intended mode of administration, the formulations used may be in the form of solid, semi-solid or liquid dosage forms, such as, for example, tablets, pills, capsules, liquids, suspensions, or the like, preferably in unit dosage forms suitable for administration of precise dosages. The formulations may include conventional pharmaceutical carriers or excipients as well as the other constituents of the composition, and may include other pharmaceutical agents, carriers, adjuvants, etc., such as, for example, flavouring agents, colouring agents and preservatives which will not affect the therapeutic activity of the composition.

Such flavouring agents include extracts and essences, either natural or artificial, of various fruits, nuts and spices such as, for example, almond extract, lemon extract, orange extract, peppermint extract and vanilla extract. In certain applications, it may be desirable to imitate the appearance and taste of an alcoholic beverage. In such cases, non-alcohol containing extracts or essences which imitate the flavour of alcoholic beverages (for example, rum extract or brandy extract among others) may be employed.

Such colouring agents include any of the colouring agents, the use of which is permitted for colouring foods or drugs under the regulations of any of the health regulatory agencies such as the Food and Drug Administration in the United States. Non-limiting examples of such colouring agents are acid fuchsin, -caramel, carbon black, ~-carotene, eosin, indigo, iron oxide and ponceau, among others.

-For oral administration, a pharmaceutically acceptable non-toxic formulation can be formed by the incorporation of any of the normally employed excipients, such as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium _ 9 - 1 33668 1 stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, magnesium carbonate, and the like. Other suitable pharmaceutical carriers and their formulations are described in "R~m~ngton's Ph~rm~ceutical Sciences-' by E. W. Martin. Such formulations take the form of solutions, suspensions, tablets, granules, effervescent granules, pills, capsules, powders, and the like.

Parenteral administration is generally characterized by injection, either subcutaneously, intramuscularly or intravenously. Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution or suspension in liquid prior to injection, or as emulsions. Suitable excipients are, for example, water, saline, mannitol, dextrose, glycerol or the like. In addition, if desired, the formulations to be administered may also contain minor amounts of non-toxic auxiliary substances such as wetting or emulsifying agents, pH
buffering agents and the like such as for example, sodium acetate, sorbitan monolaurate, triethanolamine oleate, etc.
Other suitable pharmaceutical carriers and their formulations are described in "R~minston's Pharm~ceutical Sciences" by E. W.
Nartin.

In most circumstances, all of the components of the composition of the present invention will be present in one formulation, such as one tablet or one injectable solution. In some circumstances, it may be desirable to provide a plurality of formulations, each formulation containing one or more of the components of the composition, all of the formulations together forming a complete composition according to the present invention. Thus, for example, the composltion may be present in a number of individual tablets, one tablet containing the vitamins, another the defence substances, another the amino lo - 1 33668 1 acids, etc. All such variations are considered to be encompassed by the present invention.

The amount of the composition administered will be dependent on the subject being treated, the severity of the affliction, and the manner or form of administration. In any case, a therapeutically effective amount of the composition either alone or in combination with various excipients listed above or otherwise known will be administered. For the purposes of this invention, a therapeutically effective amount of the composition is expressed in terms of the amounts of the active ingredients.

Thus, for the activated liver composition, a total dosage in the range of from about 1 mg/kg of body weight to about 20 mg/kg is effective. More preferably, the dosage would be in the range of from about 1 mg/kg to about 10 mg/kg and most preferably from about 1 mg/kg to about 3 mg/kg.

For the glucuronic acid derivatives it has been found that a total dosage in the range of from about 1 mg of the derivative per kg of body weight to about 50 mg/kg is effective. More pxeferably, the dosage would be in the range of from about 5 mg/kg to about 30 mg/kg and most preferably from about 12 mg/kg to about 24 mg/kg.

For thioctic acid and its derivatives, in particular thioctamide, the total dosage is in the range of from about 0.1 mg/kg of body weight to about 10 mg/kg. More preferably, the dosage would be in the range of from about 0.1 mg/kg to about 3 mg/kg and most preferably from about 0.1 mg/kg to,about 1 mg/kg.

For cicloxillic acid and its derivatives, the total dosage is in the range of from about 1 mg/kg of body weight to about 20 mg/kg. More preferably, the dosage would be ln the range of from about 1 mgtkg to about 10 mg/kg and most preferably from about 1 mg/kg to about 3 mg/kg.

For silymarin group compounds, and in particular silybin, the total dosage is in the range of from about 0.1 mg/kg of body weight to about 10 mg/kg. More preferably, the dosage would be in the range of from about 0.3 mg/kg to about 8 mg/kg and most preferably from about 0.5 mg/kg to about 4 mg/kg.

For citiolone, the total dosage is in the range of from about 1 mg/kg of body weight to about 20 mg/kg. More preferably, the dosage would be in the range of from about 1 mg/kg to about 10 mg/kg and most preferably from about 1 mg/kg to about 3 mg/kg.

For compositions containing combinations of any of the above defence substances, each of the individual components may be present in the ranges outlined above.

The activated liver composition which may be used in the composition of the invention is preferably prepared through an alkaline extraction process. The alkaline extraction can be accomplished by any of the known alkaline extraction agents.
Among such agents are the alkali metal and alkaline earth metal hydroxides, preferably potassium hydroxide.

The process involves contacting freshly harvested, finely ground animal livers, preferably beef and/or chicken, with an alkaline solution containing a heavy metal compound which is an essential normal dietary requiremer~, preferably,a zlnc compound, most preferably zinc carbonate, at an elevated temperature, preferably in the range of about 50 to about 80 degrees centigrade, most preferably at about 60 degrees ~~' 12 1 33668 1 centigrade. The process is allowed to continue for about 24 to about 60 hours, preferably about 48 hours, using indlrect heat.
Thereafter, the mixture is cooled to room temperature, filtered and the filtrate processed to form a fine powder. This may be accomplished, for example, through freeze drying and milling the resultant freeze dried cake to a very fine powder.

This powder may be analyzed for Vitamin B12 ~cyanocobalamin) content and the preparation adjusted so that there is at least about 100 micro-grams of Vitamin B12 present per 100 grams of dried, activated liver composition. If desired, an anti-oxidant such as dl-a-tocopheryl acetate may be added to the final mix. Preservatives may also be added if deemed necessary. The activated liver composition is sealed and stored in a cool, dry place.

Use of the heavy metal compound, and preferably the zinc compound, is particularly useful as it is postulated to allow the composition to be absorbed into the bloodstream through the stomach and intestinal mucosa, and thus the composition is suitable for formulation into an oral dosage form. An oral dosage form is particularly preferable, because it allows a user to ingest the composition either before, during, or a~ter alcohol ingestion without the necessity of supervised administration.

The invention is further exemplified by the embodiments descri~-d in the following illustrative and non-limiting examples.

EXAMPT,F. 1 - 5,000 grams of freshly harvested beef liver was finely ground and added to 1 litre of a O.OSN potassium hydroxide _ 13 ` ~ 33668 1 solution containing 0.0005 grams of zinc carbonate. This solution was heated to 60 C and maintained at this temperature, using steam coils, with constant slow stirring for 48 hours.
The solution was then cooled to 25 C, filtered through a Buchner glass frit funnel, the filtrate freeze dried to produce a cake and the cake milled to a very fine powder. The freeze dried powder was analyzed for cyanocobalamin content and adjusted to contain 100 micro-grams of cyanocobalamin per 100 grams of activated liver composition. Thereafter, 10 mg of synthetic dl--tocopheryl acetate was added per 100 grams of powder as an anti-oxidant. This powder was sealed hermetically and stored.

. XAMP T .F 2 Ten (10) kilo-grams of liquid liver extract, prepared according to the standard British Pharmacopoeia (BP) method, was heated as a liquid extract in a 10 litre solution containing 0.05N potassium hydroxide and 0.001 grams zinc carbonate to 60 C and treated as in Example 1 to produce a very fine powder.
The mixture was adjusted to have a cyanocobalamin content of 100 micro-grams per 100 grams of dried activated liver. The r~sulting powder was thoroughly mixed. To the mixture was added 10 mg of dl-~-tocopheryl acetate per 100 grams of dried mix.
The mixture was sealed hermetically and stored in a cool, dry place.

EXA~PTF 3 To the powder prepared in accordance with Example 1 was added, as dried powders per kilo-gram of mixture,,the following amino acids:

40 grams cysteine 40 grams of histidine 70 grams isoleucine 100 grams leucine 50 grams threonine 30 grams valine The resulting powder was thoroughly mixed, sealed hermetically and stored in a cool, dry place.

FXAMPT.F. 4 , ....

To the powder prepared in accordance with Example 1 was added, as dried powders per kilo-gram of mixture, the following amino acids:

4 0 grams cysteine 70 grams isoleucine 100 grams leucine 80 grams lysine 30 grams methionine 50 grams phenylalanine 50 grams threonine 25 grams tryptophan 50 grams tyrosine The resulting powder was thoroughly mixed, sealed hermetically and stored in a cool, dry place.

F`,XAMPT.F. S

Tablets were formulated containing the following active ingredients:

Activated Liver composition 50 mg tprepared according to Example 3 or 4 ) Caffeine Alkaloid 15 mg Vitamin B1 4 mg Vitamin B2 4 mg Vitamin B6 3 mg Nicotinamide 15 mg Vitamin B12 10 mcg Choline Bi-tartrate 50 mg Cysteine 10 mg Inositol 15 mg F.XA~ T.F. 6 1S ~ t 33668 1 Tablets were formulated containing the following active ingredients:

Activated Liver composition 50 mg (prepared according to Example 3 or 4) Vitamin B1 4 mg Vitamin B2 4 mg Vitamin B6 3 mg Nicotinamide 15 mg Vitamin B12 10 mcg Choline Bi-tartrate 50 mg Cysteine 10 mg Inositol 15 mg F.XA~PT,F. 7 A subject group consisting of 113 individuals was divided into three equal groups, one group (the "experimental group") receiving the tablets prepared in accordance with Example 5, a second group acting as a control receiving no treatment, and a third group acting as a placebo control receiving tablets of exactly the same weight, colour and shape as the experimental group. All subjects were administered a sufficient amount of alcohol to theoretically result in an average blood alcohol level of 15 mg/dl and thereafter administered either the composition, placebo or nothing. Blood samples were drawn every fifteen minutes for the first hour after treatment and hourly thereafter for the next six hours for determination of the blood alcohol level. The alcohol in the blood system of each of the three groups was expressed as a percent of the alcohol remaining by utilizing the theoretical starting level as a base and compared.

One hour after ingesting the tablets, the experimental group had on average 40 percent of the alcohol ad~inistered r~i n i ng in their system. In contrast, both the placebo and control groups had greater than 91 percent of the alcohol remaining. After four hours, the experimental group had less ~ 16 ~ l 336681 than 5 percent of the alcohol re~ln~ng in their system, while the placebo and control groups still had 70 percent of the alcohol in their system.

F,XAMPT.F. 8 Tablets were formulated containing the following active ingredients:

Activated Liver composition 50 mg (prepared according to Example 3 or 4) Glucuronolactone 250 mg Glucuronamide200 mg Caffeine Alkaloid 15 mg Vitamin B1 4 mg Vitamin B2 4 mg Vltamin B6 3 mg Nicotinamide-15 mg Vitamin B1210 mcg Choline Bi-tartrate 50 mg Cysteine 10 mg Inositol 15 mg Tablets prepared according to either example 5 or 8 were administered to four persons (three days apart). No hangovers, headaches or nausea were reported upon waking the next morning (by any person taking both formulations on both days) after consumption of alcohol the night before.

F.XA~PT.F. 9 Tablets were formulated containing the following active ingredients:

Glucuronolactone 250 mg Glucuronamide200 mg Caffeine Alkaloid 15 mg Vitamin B1 4 mg - Vitamin B2 4 mg Vitamin B6 3 mg Nicotinamide15 mg vitamin B1210 mcg Choline Bi-tartrate 50 mg Cysteine 10 mg Inositol 15 mg ; ' ~ 17 l 33668 1 F.XAMPT.F, 1 0 Tablets were formulated containing the following active ingredients:

Glucuronamide 200 mg Caffeine Alkaloid 15 mg Vitamin B14 mg Vitamin B24 mg Vitamin B63 mg Nicotinamide 15 mg Vitamin B1210 mcg Choline Bi-tartrate 50 mg Cysteine 10 mg Inositol 15 mg T~`.X~IPT.F. 1 1 Tablets were formulated containing the following active l ingredients:
Glucuronolactone 250 mg Caffeine Alkaloid 15 mg Vitamin B14 mg Vitamin B24 mg Vitamin B63 mg Nicotinamide 15 mg ! Vitamin B1210 mcg Choline Bi-tartrate 50 mg - Cysteine 10 mg Inositol 15 mg F.XAMPT,F. 12 :' , A single dose powder was formulated containing the following composition:

Activated Liver composition 50 mg (prepared according to Example 3 or 4) Glucuronolactone 250 mg Glucuronamide 200 mg Thiamine HCl2 mg . Caffeine Citrate 50 mg : Vitamin B121 mcg : Potassium Chloride 135 mg Sodium Chloride 160 mg - Sodium Bicarbonate 180 mg ,. Citric Acid50 mg .

. I .

18 l 33668 1 The formulations were suspended in water and administered to three persons ingesting alcohol on two separate occasions three days apart shortly after mixing. All three persons reported (on both occasions) that they felt that they did not want to drink anymore. They all stopped drinking for the night after having taken the formulations.

F.XA~PT .F, 1 3 A liquid formulation was prepared by suspending in 50 ml of water the following active ingredients:

Glucuronolactone 250.0 mg Glucuronamide 200.0 mg Thiamine HCl 2.0 mg Vitamin B12 1.0 mcg Potassium chloride 135.0 mg Sodium chloride 160.0 mg Sodium bicarbonate 180.0 mg Citric acid 50.0 mg Dextrose 9.475 g In a further version, 50.0 mg of caffeine citrate, as well as, masking and flavouring agents and preservatives were added to the above formulation.

F.XAMPT.F. 1 4 An effervescent granular formulation was prepared containing the following active ingredients:

Glucuronolactone 250.0 mg Glucuronamide 200.0 mg Ascorbic acid 250.0 mg Vitamin B12 5.0 mcg Potassium chloride 135.0 mg Sodium chloride 160.0 mg Sodium bicarbonate 180.0 mg Citric acid 50.0 mg Dextrose 9.475 g In a further version, 50.0 mg of caffeine citrate was added to the above formulation.

F.XAMPT,F. 15 A phospholipid mixture was prepared by mixing phospholipids in the following proportions:

Phosphatidylcholine (PC) appr 15.0%
Phosphatidylethanolamine (PE) appr 10.5%
Cardiolipin(CL) appr 2.4%
Phosphatidylserine (PS) plus Phosphatidylinositol (PI) appr 2.1%
Linoleic Acid and Oleic Acid appr 70.0$ (50:50) FXA~IPT.F, 1 6 .

Tablets were formulated containing the following active ingredients:

. .
Activated Liver composition 50.0 mg (Prepared according to Example 4) Phospholipid mixture 160.0 mg (Prepared according to Example 15) Folic Acid .1 mg Vitamin B1 4.0 mg Vitamin B12 5.0 mcg Vitamin B6 2.5 mg Choline Bitartrate 50.0 mg Cysteine 10.0 mg Inositol 15.0 mg I Nicotinamide 15.0 mg ! Vitamin E Acetate5.0 mg (as anti-oxidant) ~' In a further version, 10.0 mg of caffeine citrate was added to --- the above formulation.
. .

F~XAMPT.F. 1 7 Tablets were formulated containing the following active ingredients:

Activated Liver composition 50.0 mg Thioctamide 10.0 mg Folic Acid .1 mg Vitamin B1 4.0 mg Vitamin B12 5.0 mcg Vitamin B 6 2.5 mg Choline Bitartrate 50.0 mg Cysteine 10.0 mg Inositol 15.0 mg Nicotinamide 15.0 mg .

In a further version, 10.0 mg of caffeine citrate was added to the above formulation.

IPT.~, 1 8 Tablets were formulated containing the following active ingredients:

Activated liver composition 50.0 mg Cicloxillic acid 40.0 mg Vitamin Bl 4.0 mg Vitamin B12 5.0 mcg Vitamin B6 2.5 mg Choline Bitartrate 50.0 mg Cysteine 10.0 mg Inositol 15.0 mg Nicotinamide 15.0 mg In a further version, 10.0 mg of caffeine citrate was added to the above formulation.

PT.F~ 1 9 Tablets were formulated containing the following active ingredients:

Activated liver composition 50.0 ms Silymarin 30.0 mg Vitamin B1 4.0 mg ~ 21 l 336681 Vitamin B12 5.0 mcg Vitamin B6 2.5 mg Choline Bitartrate 50.0 mg Cysteine 10.0 mg Inositol 15.0 mg Nicotinamide 15.0 mg In a further version, 10.0 mg of caffeine citrate was added to the above formulation.

F~XAMPT .~ 2 0 Tablets were formulated containing the following active ingredients:

Activated liver composition 50.0 mg Citiolone 50.0 mg Cysteine 10.0 mg Vitamin Bl 4.0 mg Vitamin B12 5.0 mcg Vitamin B6 2.5 mg Choline Bitartrate 50.0 mg Inositol 15.0 mg Nicotinamide 15.0 mg In a further version, 10.0 mg of caffeine citrate was added to the above formulation.

While the invention has been described in reference to specific embodiments thereof, it should be understood by those skilled in the art that various changes can be made and equivalents may be substituted without departing from the true spirits and scope of the invention. All such modifications are intended to be within the scope of the claims appended hereto.

Claims (62)

THE EMBODIMENTS OF WHICH AN EXCLUSIVE PROPERTY OR
PRIVILEGE IS CLAIMED ARE AS FOLLOWS:

1. A process for preparing an activated liver composition comprising, contacting finely ground animal liver with an alkaline solution containing a heavy metal compound which is an essential normal dietary requirement at a temperature of about 50 to about 80 degrees centigrade for about 24 to about 60 hours.

2. A process as claimed in claim 1, wherein said heavy metal compound is a zinc compound.

3. A process as claimed in claim 2, wherein said zinc compound is zinc carbonate.

4. A process as claimed in claim 3 wherein said alkaline solution contains an alkali metal or alkaline earth metal hydroxide.

5. A process as claimed in claim 4, wherein said alkaline solution contains potassium hydroxide.

6. A process as claimed in claim 1, wherein said temperature is about 60° C.

7. A process as claimed in claim 6, wherein said heavy metal compound is a zinc compound.

8. A process as claimed in claim 7, wherein said zinc compound is zinc carbonate.

9. A process as claimed in claim 8, wherein said alkaline solution contains an alkali metal or alkaline earth metal hydroxide.

10. A process as claimed in claim 9, wherein said alkaline solution contains potassium hydroxide.

11. A process as clalmed in claim 1, wherein said time is about 48 hours.

12. A process as claimed in claim 11, wherein said heavy metal compound is a zinc compound.

13. A process as claimed in claim 12, wherein said zinc compound is zinc carbonate.

14. A process as claimed in claim 13, wherein said alkaline solution contains an alkali metal or alkaline earth metal hydroxide.

15. A process as claimed in claim 14, wherein said alkaline solution contains potassium hydroxide.

16. A process for preparing an activated liver composition comprising, contacting finely ground beef liver with a potassium hydroxide solution containing zinc carbonate at a temperature of about 60 degrees centigrade for about 48 hours.

17. A process according to claim 16, further comprising, cooling the composition to room temperature, processing said composition to form a fine powder, and adjusting the vitamin B12 content of said composition to be about 100 microgram per 100 grams of composition.

18. A process according to claim 17, further comprising, mixing the composition as produced in claim 17 with one or more additives selected from the group consisting of amino acids, lipids, vitamins and other nutrients.

19. A process as claimed in claim 18, wherein said amino acids are one or more amino acids selected from the group consisting of choline and derivatives, inositol, asparginine, glutamine, aspartate, alpha-amino-N-butyric acid, arginine, cysteine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tryosine and valine.

20. A process according to claim 18, wherein said vitamins are one or more vitamins selected from the group consisting of Vitamin B1, Vitamin B2, Vitamin B6, folic acid, nicotinamide, Vitamin B12 and ascorbic acid.

21. A process according to claim 18, wherein said lipids are one or more lipids selected from the group consisting of glycerophosphates, glycerylphosphorylcholine, lysophospholipids, lysophosphatidylcholine, phosphatidic acid, dimyristoylphos-phatidylcholine, 1,2-dipalmitoylphosphatidylcholine, phosphatidylglycerols, phosphoinositide, phosphatidylcholine, phosphatidylethanolamine, cardiolipin, phosphatidylserine, phosphatidylinositol, linoleic acid and oleic acid.

22. A process according to claim 18 wherein said essential nutrients are one or more essential nutrients selected from the group consisting of choline, inositol, and electrolyte replacing compounds which aid in replacement of electrolytes lost by the body.

23. A process according to claim 22 wherein said electrolyte replacing compounds are one or more electrolyte replacing compounds selected from the group consisting of sodium and potassium salts.

24. A process according to claim 23 wherein said sodium and potassium salts are one or more sodium and potassium salts selected from the group consisting of potassium chloride, sodium chloride, and sodium bicarbonate.

25. A composition for improving the body's rate of removing consumed alcohol said composition being selected to enhance the body's natural defence mechanisms, said composition comprising an activated liver composition containing a heavy metal compound which is an essential normal dietary requirement or at least two defence substances selected from the group consisting of said activated liver composition, glucuronic acid and its derivatives, thioctic acid and its derivatives, cicloxillic acid and its derivatives, citiolone and silymarin group compounds.

26. A composition according to claim 25 wherein said activated liver composition is prepared according to the process of claim 1.

27. A composition according to claim 25 further comprising one or more additives selected from the group consisting of amino acids, vitamins, lipids and other essential nutrients which are generally depleted as a result of alcohol consumption.

28. A composition according to claim 26 further comprising one or more additives selected from the group consisting of amino acids, vitamins, lipids and other essential nutrients which are generally depleted as a result of alcohol consumption.

29. A composition according to claim 27 wherein said amino acids are one or more amino acids selected from the group consisting of choline, inositol, cysteine, histidine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine and valine.

30. A composition according to claim 28 wherein said amino acids are one or more amino acids selected from the group consisting of choline, inositol, cysteine, histidine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine and valine.

31. A composition according to claim 27 wherein said vitamins are one or more vitamins selected from the group consisting of Vitamin B1, Vitamin B2, Vitamin B6, folic acid, nicotinamide, Vitamin B12 and ascorbic acid.

32. A composition according to claim 28 wherein said vitamins are one or more vitamins selected from the group consisting of Vitamin B1, Vitamin B2, Vitamin B6, folic acid, nicotinamide, Vitamin B12 and ascorbic acid.

33. A composition according to claim 27, wherein said lipids are one or more lipids selected from the group consisting of glycerophosphates, glycerylphosphorylcholine, lysophospholipids, lysophosphatidylcholine, phosphatidic acid, dimyristoylphosphatidylcholine, 1,2-dipalmitoyl-phosphatidylcholine, phosphatidylglycerols, phosphoinositide, phosphatidylcholine, phosphatidyl-ethanolamine, cardiolipin, phosphatidylserine, phosphatidylinositol, linoleic acid and oleic acid.

34. A composition according to claim 28, wherein said lipids are one or more lipids selected from the group consisting of glycerophosphates, glycerylphosphorylcholine, lysophospholipids, lysophosphatidylcholine, phosphatidic acid, dimyristoylphosphatidylcholine, 1,2-dipalmitoyl-phosphatidylcholine, phosphatidylglycerols, phosphoinositide, phosphatidylcholine, phosphatidyl-ethanolamine, cardiolipin, phosphatidylserine, phosphatidylinositol, linoleic acid and oleic acid.

35. A composition according to claim 27 wherein said essential nutrients are one or more essential nutrients selected from the group consisting of choline, inositol and electrolyte replacing compounds which aid in replacement of electrolytes lost by the body.

36. A composition according to claim 28 wherein said essential nutrients are one or more essential nutrients selected from the group consisting of choline, inositol and electrolyte replacing compounds which aid in replacement of electrolytes lost by the body.

37. A composition according to claim 35 wherein said electrolyte replacing compounds are one or more electrolyte replacing compounds selected from the group consisting of sodium and potassium salts.

38. A composition according to claim 36 wherein said electrolyte replacing compounds are one or more electrolyte replacing compounds selected from the group consisting of sodium and potassium salts.

39. A composition according to claim 37 wherein said sodium and potassium salts are one or more sodium and potassium salts selected from the group consisting of potassium chloride, sodium chloride, and sodium bicarbonate.

90. A composition according to claim 38 wherein said sodium and potassium salts are one or more sodium and potassium salts selected from the group consisting of potassium chloride, sodium chloride, and sodium bicarbonate.

41. A composition according to claim 27 comprising glucuronolactone, glucuronamide, thiamine HC1, vitamin B12, potassium chloride, sodium chloride, sodium bicarbonate, citric acid, flavouring agents, preservatives, dextrose and pharmaceutically acceptable excipients.

42. A composition according to claim 27 or 28 comprising said activated liver composition, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, phosphatidylcholine, phosphatldylethanolamine, cardiolipin, phosphatidylserine, phosphatidylinositol, linoleic acid, oleic acid, folic acid, vitamin B1, vitamin B12, vitamin B6, choline bitartrate, cysteine, inositol, nicotinamide, vitamin E acetate and pharmaceutically acceptable excipients.

43. A composition according to claim 27 or 28 comprising said activated liver composition, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, caffeine alkaloid, vitamin B1, vitamin B2, vitamin B6, nicotinamide, vitamin B12, choline bi-tartrate, cysteine, inositol and pharmaceutically acceptable excipients.

44. A composition according to claim 27 or 28 comprising said activated liver composition, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, glucuronolactone, glucuronamide, caffeine alkaloid, vitamin B1, vitamin B2, vitamin B6, nicotinamide, vitamin B12, choline bi-tartrate, inositol and pharmaceutically acceptable excipients.

45. A composition according to claim 27 comprising glucuronolactone, glucuronamide, activated liver composition, thioctic acid, thiamine HC1, vitamin B12, folic acid, potassium chloride, sodium chloride, sodium bicarbonate, citric acid, flavouring agents, preservatives, dextrose and pharmaceutically acceptable excipients.

46. A composition according to claim 27 or 28 comprising said activated liver composition, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, glycerophosphates, glycerylphosphorylcholine, lysophospholipids, lysophosphatidylcholine, phosphatidic acid, dimyristoylphosphatidylcholine, 1,2-dipalmitoylphosphatidylcholine, phosphatidylglycerols, phosphoinositide, phosphatidylcholine, phosphatidylethanolamine, cardiolipin, phosphatidylserine, phosphatidylinositol, linoleic acid, oleic acid, folic acid, vitamin B1, vitamin B12, vitamin B6, choline bitartrate, inositol, nicotinamide, vitamin E acetate and pharmaceutically acceptable excipients.

47. A composition according to claim 27 or 28 comprising said activated liver composition, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, caffeine alkaloid, vitamin B1, vitamin B2, vitamin B6, folic acid, nicotinamide, vitamin B12, choline bi-tartrate, inositol and pharmaceutically acceptable excipients.

48. A composition according to claim 27 or 28 comprising said activated liver composition, cysteine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, glucuronolactone, glucuronamide, caffeine alkaloid, vitamin B1, vitamin B2, vitamin B6, folic acid, nicotinamide, vitamin B12, choline bi-tartrate, inositol and pharmaceutically acceptable excipients.

49. A composition according to claim 27 or 28 comprising said activated liver composition, thioctamide, folic acid, vitamin B1, vitamin B12, vitamin B6, choline bitartrate, cysteine, inositol, nicotinamide and pharmaceutically acceptable excipients.

50. A composition according to claim 27 or 28 comprising said activated liver composition, cicloxillic acid, vitamin B1, vitamin B12, vitamin B6, choline bitartrate, cysteine, inositol, nicotinamide and pharmaceutically acceptable excipients.

51. A composition according to claim 27 or 28 comprising said activated liver composition, silymarin, vitamin B1, vitamin B12, vitamin B6, choline bitartrate, cysteine, inositol, nicotinamide and pharmaceutically acceptable excipients.

52. A composition according to claim 27 or 28 comprising said activated liver composition, citiolone, cysteine, vitamin B1, vitamin B12, vitamin B6, choline bitartrate, inositol, nicotinamide and pharmaceutically acceptable excipients.

53. An oral dosage form of a composition according to claims 25, 26 or 27.

54. An oral dosage form of a composition according to claim 28, 29 or 30.

55. An oral dosage form of a composition according to claim 31, 32 or 33.

56. An oral dosage form of a composition according to claim 34, 35 or 36.

57. An oral dosage form of a composition according to claim 37, 38 or 39.

58. An oral dosage form of a composition according to claim 40, 41 or 42.

59. An oral dosage form of a composition according to claim 43, 44 or 45.

60. An oral dosage form of a composition according to claim 46, 47 or 48.

61. An oral dosage form of a composition according to claim 49, 50 or 51.

62. An oral dosage form of a composition according to claim 52.