Indian Patents. 268554:"A COMPOSITION FOR USE AS AN ADDITIVE FOR USE IN AMELIORATING THE EFFECTS OF ALCOHOL"

Title of Invention	"A COMPOSITION FOR USE AS AN ADDITIVE FOR USE IN AMELIORATING THE EFFECTS OF ALCOHOL"
Abstract	A composition for use as an additive in alcohol for human consumption and is useful in ameliorating the effect of alcohol on the human system, said composition comprising a mixture of a choline compound and ascorbic acid, the choline compound being present in an amount of 50 mg to 3000 mg and the ascorbic acid being present in an amount of 50 mg to 4000mg per 70 ml of 100% alcohol.

Full Text	COMPOSITION FOR MODERATING EFFECT OF ALCOHOL ON HUMAN BODY Field of the invention The present invention relates to a composition for moderating the effect of alcohol on a human body. More particularly, the present invention relates to a composition which is useful for moderating the intoxicating effect of alcohol consumption on a human body without requiring reduction in the level of alcohol consumption. The present invention also relates to a process to increase plasma free choline level in a subject in order to prevent initial stages of liver steatosis. The present invention also relates to a composition for the reduction and/or prevention of liver steasosis in a subject. The present invention also enables reduction of fatty tissue deposits and alcohol related liver degeneration. The present invention also relates to a composition which alter lipid metabolism and which possesses preventive effect on liver degeneration. Background of the invention and prior art Alcohol consumption is known to cause serious damage to the human body. A heavy or even moderate drinker faces The health risks that a heavy drinker faces are obesity, addiction, ulcers, brain damage, liver cirrhosis etc. Also, the oxidation of fatty acid is impaired in the mitochondria. These fats accumulate in the liver to produce fatty liver. Alcohol can supply excess calories leading to weight gain. Alcohol (all varieties which as such are legally sold and imbibed by human beings) is a depressant. Imbibing alcohol slows down the central nervous system resulting therefore in a slower transmission of messages through the nerve fibers. Among the effects of alcohol are a marked tendency, in the imbiber to become apparently relaxed, slurring of speech, slower reactions and reflexes, and varied mood swings. The above effects are attributable to the fact that alcohol replaced water molecules around the nerve cells, thereby interfering with the movement of electrically charged atoms, which are responsible for transmission of messages in the nervous system. Alcohol also slows down the movement of the chemical messenger molecules which carry information from cell to cell in the human body. Lipotropic agents are substances that stimulate removal of excess fat from liver. Such substances include choline, inositol, methionine, Vitamin B12, folic acid etc. Studies suggest that choline be studied for treating fat disorder, hepatic degeneration, but never referenced in management of alcohol damage. Choline deficiency has been known to cause fatty infiltration of liver, thus a deficiency in choline may result in the inability of the liver to transport fatty acid such as triglyceride. Study show that hepatic steatosis in many long term total parentral nutrition patients may be caused by a deficiency in plasma free choline and such deficiencies may be reversed by pharmacologically accepted salt of choline, that increases free choline and decreases hepatic steatosis. It is known that choline by itself fails to prevent liver fibrosis in alcohol (ethanol) fed baboons and in fact causes toxicity [Leiber, et al, Hepatology 1985, Jul-Aug, 5(4), 561 - 572]. It is also reported that ethanol alone may affect hepatic one carbon metabolism, which requires the participation of both methionine and choline in transfer of methyl groups [Trimble et al, Hepatology, 1993,18(4), 984 - 989]. The effect of concomitant use of choline salt along with alcohol consumption on reducing the after effects of alcohol consumption was gone unnoticed. The prior art does not suggest or teach the use of controlling after effects of consumption of alcohol using choline by itself or in synergistic combination with another substance. The use of choline to treat fatty liver and alcoholic in etiology has not proven to be consistently effective. Acetyl choline is synthesized from choline and acetyl COA by acetyl choline transferase. Choline is transported between the brain and plasma by a bidirectional system localized in the endothelium of the brain capillaries. This system operates by facilitated diffusion and the amount of choline available to the central neurons in the nervous system thus varies as a function of the concentration of choline in plasma. Conventionally, the needs of tissues for choline are met by both exogeneous (dietary) sources and endogeneous (metabolic) sources. Biosynthesis of choline occurs by transmethylation of ethanolamine with the methyl group of methionine or by a series of reactions requiring vitamin B12 and folate as cofactors. Due to the synthesis of choline from other methyl donors, provision of a well balanced diet is usually effective in alleviating the symptoms of hepatic damage. However, what is observed in clinical practice is that heavy imbibers of alcohol also suffer from deficient diet. As a result hepatic damage due to imbibing of alcohol is not remedied by a balanced diet Since the availability of brain choline and brain acetylcholine depends on facilitated diffusion, it is important to ensure that optimum levels of plasma choline are present for optimum brain activity. Alcohol itself being a depleting agent of choline, results in brain dysfunction. It is also observed that chronic alcohol abuse is also a significant cause for malnutrition, including vitamin and mineral deficiency, particularly of vitamins A, Bl to B12 and C. Vitamin and mineral metabolism is disrupted due to liver damage caused by long term alcohol abuse. Alcohol also has a diuretic effect as a result of the reduction of the amounts of vasopressin leading to further depletion of vitamins and minerals from the human body. Vitamin C is a known anti-oxidant which protects all cells from oxidative damage and is also a proficient anti-carcinogenic nutrient. Vitamin C blocks the creation of the carcinogen nitrosamine. Objects of the invention The main object of the invention is to provide a composition for use as an additive in alcohol intended for human consumption, which reduces or ameliorates the negative effect of alcohol consumption on the human body. Summary of the invention Accordingly the present invention provides a composition for use as an additive in alcohol for human consumption and is useful in ameliorating the effect of alcohol on the human system, said composition comprising a mixture of a chloine compound and ascorbic acid, the choline compound being present in an amount of 50 mg to 3000 mg and the ascorbic acid being present in an amount of 50 mg to 4000mg per 70 ml of 100% alcohol. In one embodiment of the invention, the choline compound comprises choline chloride. In yet another embodiment of the invention, the amount of choline chloride in the composition is 490 mg and the amount of ascorbic acid is 750 mg, both amounts being in based on 70 ml of 100% alcohol. The present invention also provides an alcohol formulation comprising a combination of alcohol for human consumption and an additive composition, and wherein for every 70ml of 100% alcohol, the additive composition comprises a mixture of a choline compound and ascorbic acid, the choline compound being present in an amount of 50 mg to 3000 mg and the ascorbic acid being present in an amount of 50 mg to 4000mg. In one embodiment of the invention, the choline compound comprises choline chloride. In yet another embodiment of the invention, the amount of choline chloride in the composition is 490 mg and the amount of ascorbic acid is 750 mg, both amounts being in based on 70 ml of 100% alcohol. In another embodiment of the invention, the alcohol component can be any alcohol intended and legally sold or distributed for human consumption such as for example the group consisting of whisky of any kind, toddy, rum, beer, gin, vodka, wine of any type, and brandy, medicinal alcohol, cognac, port, sherry, rice wine, sake, liqueurs, schnapps and the like. The compositions of the invention are synergistic admixtures showing improved and unexpected properties over the aggregate properties of the individual ingredients and are not a mere aggregation of the properties of the ingredients. Detailed description of the invention A composition is provided in accordance with the invention which comprises essentially of a combination of Vitamin C and choline chloride. The interaction between choline chloride and Vitamin C has several beneficent effects on alcohol abuse induced problems on the human body. For example, the composition of the invention serves to replenish the choline levels in the brain thereby repairing the brain dysfunction that occurs on imbibing alcohol. In addition, vitamin C functions also as a regular nutrient replenishing the vitamin levels in the body. These however are merely known properties of the two ingredients of the composition. More importantly, choline chloride and vitamin C act synergistically to ensure that hepatic damage to the liver in terms of liver steatosis is prevented/minimized. This can be ascribed to the interaction between choline chloride and Vitamin C whereby the anti-oxidant nature of vitamin C is enhanced, due to the participation of ascorbate in oxido-reducing process connected with ethanol metabolism. Another significant advantage is that the composition of the invention can be administered along with the alcohol itself, without impairing any sensory pleasure that the imbiber obtains on imbibing alcohol. It has now been observed after detailed clinical trials that a mixture of a choline compound such as choline chloride and ascorbic acid exhibit a surprising effect in alleviating the metabolic disturbances caused by alcohol particularly increase in Blood pressure, mean corpuscular volume (mcv), lipid content in circulation and most important increased liver enzymes. These effects are quite surprisingly particularly in the view of the fact that such effects are not observed when administering either choline chloride or ascorbic acid alone. Thus according to the present invention choline chloride and ascorbic acid must be used in combination. Source of choline in diet tend to be found in high fat, high cholesterol food such as meat, liver, egg, which should be avoided by the alcohol drinker and person with compromised liver and person who tends to be obese. Therefore pursuant to the present invention additional choline variant is preferably ingested orally. Choline variant is a compound currently approved for human use. For alleviation of the result of drinking, the choline variant is preferably concomitantly administered with the drinking. Ideal dose may vary according to amount of alcohol consumption. The effectiveness of composition in alleviation of alcohol abuse and liver necrosis concerning alcohol consumption has been demonstrated herein. The choline variant effective for the disclosed uses include any substance of which choline itself is a metabolite. Other choline variants with different substituent groups wold be expected to exhibit similar properties. Choline chloride is administered in order to increase blood levels of choline and thereby to increase the level of acetylcholine in the brain. Administration result in desirable behavioral modification and in alleviation of psychogenic and nervous symptomatology associated with alcohol abuse. Most commonly associated psycholenic symptoms of alcohol abuse comprises anxiety, depression, decreased cognition, hostility and violence. Technically alcohol is referred as a depressant, that is it slows down the activity of central nervous system, so that messages take longer to travel along nerve fibers. An alcohol consumer becomes slower in movement and speech becomes slurred. The amount of choline available to central neurons varies as a function of the concentration of choline in plasma. When choline chloride is given, a sequential increase in the concentration of plasma choline, brain choline and brain acetylcholine is expected. The need of the tissue for choline are met from both exogenous (=dietary) and endogenous source. Biosynthesis of choline occurs by transmethylation of ethanolamine with the methyl group of methionine or by a series of reactions requiring vitamin B12 and foliate as cofactors. Thus and adequate supply of methyl group donors in diet is desirable, to protect against the hepatic accumulation of lipid. Because of synthesis of choline from other methyl donors, provision of well-balanced diet is just as effective in alleviating the symptoms of hepatic damage. Available facts support the conclusion that the synthesis of choline is not always sufficient to meet human requirement of choline. Chronic alcohol abuse is a significant cause of malnutrition including vitamin and mineral deficiency, particularly B6, B12 and C. Alcohol has a large energy content, so those who drink a lot, often eat less food, thereby increasing the risk of vitamin and mineral deficiency. Alcohol has a diuretic effect by reducing the amount of vasopressin which leads to many vitamins and minerals being flushed out of body. At the same time alcohol blocks the uptake of vitamin and mineral by irritating the mucous membrane of alimentary canal. The need for the nutrients is increased, because the alcohol causes tissue damage, which then needs repair. Additional supply of choline chloride can help in repairing the tissue damage by intermediary metabolism. The consumption of alcohol also results in the formation of two very toxic compounds - acetaldehyde and malondialdehyde. These compounds generate massive free radical damage to cells throughout the body. The free radical damage generated by this alcohol metabolite creates an effect in the body similar to radiation poisoning, resulting in people feeling sick the day after consuming too much alcohol. The composition of the invention helps to reduce the concentration of aldehyde. It is believed that this occurs due to the interaction of the composition of the invention in oxido reducing process, as a result of which the mitochondria remain healthy and clear the aldehyde at faster and better rate. The beneficial effects could also be due to reduced aldehyde concentration thereby limiting structural damage to liver cell and restores better mitochondria function. Another potential reason could be the reduction in hepatic cell necrosis which can be interpreted by liver enzyme, AST/ALT/GGT and the like. Healthy hepatocytes also favour reduction in concentration of aldehydes. The additive composition of the invention provides liver protection by altering the alcohol metabolism in the body by enhancing the aldehyde clearance by mitochondria thereby reducing the aldehyde concentration. The improved oxido reducing process due to composition of the invention results in the mitochondria clearing the acetaldehyde at better efficiency and resulting in reduced aldehyde concentration in body tissue in alcoholics. This results in restricted hepatic cell necrosis due to aldehyde that is manifested by reduced level of liver enzymes. Increased systolic B.C. is another complication supposed to be related with hepatic damage due to aldehyde in alcoholics. Efficacy of composition of the invention to improve the oxidative metabolism were confirmed by test result data of serum cholesterol to high density lipid (HDL) ratio of the subjects indicated in the Table 2 below. Lipid oxidation shifts towards the healthier side, and at the same time reduced mcv also support the fact of improvement of lipid oxidative metabolism. Other subjects treated with higher doses of content of composition showed improvement in depression, memory impairment and muscular co-ordination generally encountered in alcoholics. Few subjects of the same group also reported no sluggish liver on the next day of drinking and countable improvement on gastric ulcer if were present. The composition of the invention can also be used in encapsulated form with conventional encapsulates. As a consequence of the hepatic metabolism of alcohol a series of metabolic alteration take place, which are responsible for liver damage. Metabolism in the hepatocyte: There are three systems, which are able to metabolise ethanol - ADH - alcohol dehydrogenase, the microsomal ethanol oxidising system (MEOS) and catalase. Each of these lead to acetaldehyde production, being acetaldehyde the toxic metabolite and ethanol. In second step acetaldehyde is metabolised to acetate by mitochondria. Acetate produced in liver are released in to blood and oxidation to CO2, fatty acids and water. Metabolic changes: During ethanol oxidation hydrogen is transferred from the substrate to cofactor NAD, converting it to its reduced form NADH. The excess of reduced equivalents mainly NADH produces a change in redox system. The redox imbalance is responsible for the metabolic alterations, which favors liver damage. Increase in NDH/NAD favors the synthesis of fatty acid. The mechanism by which fatty acids are accumulated in the liver in the form of tryglycerides is complex. Increased MEOS activity is produced as a consequence of chronic alcohol consumption and this affects the CYP2E1 (ethanol inducible fraction of the cytochromP450) which has a relative high redox potential leads to formation of free oxygen radical and oxidative stress. Acetaldehyde diminishes the activity of mitochondria to oxidise fatty acid as well as other functions. These mitochondrial dysfunction leads to higher level of acetaldehyde in the plasma causing of damage. Regular alcohol consumption causes significant reduction in mitochondrial capacity to oxidize acetaldehyde. This is due to lower capacity of mitochondria to deoxidize NADH. The composition of the invention helps to revive the mitochondrial function and thereby helps to get back the normal ration of NADH/NAD that prevents the liver damages caused by alcohol intoxication. Increased level of acetaldehyde due to alcohol consumption, lead to liver cell-necrosis, resulting in high levels of liver enzymes. The composition of the invention when added to liquor restores mitochondrial function thereby enabling the mitochondria to oxidize the acetaldehyde and reducing the concentration of acetaldehyde in blood, thereby preventing hepatic cell damage which result in the decreased level of liver enzymes i.e. AST/ALT/GGT. (As shown in table). Composition added liquor fights with oxidation stress also, which is generally caused by alcohol intoxication and protects the hepatocytes from another side. Blood Pressure (B.P.) Elevated BP is a very common feature in alcohol users. Rise in BP is assumed due to direct toxic effect and hepatic damage due to alcohol and its metabolite. Composition added liquor restricts the hepatic damage to the liver and helps to get back the BP towards the normal limits, (see Table 2) MCV Lipid changes in blood and toxic effects of alcohol and its metabolite may cause the MCV to increase and a picture of macrocytosis is often encountered in alcoholics. MCV value gets to normal, if person passes a period of minimum 135 days under test trial, (see table 2) LIPID Due to alcohol intoxication lipid starts to deposit in liver and so also the lipid content in blood circulation increases. Lipid profile disturbs and shifts to higher level of serum cholesterol and ratio of S. cholesterol/HDL (HDL = High Density Lipid) increases. During the trial phase of composition added liquor, the contents of composition makes a fall in the ration of serum cholesterol/HDL. EXAMPLE Dose related may vary in different persons depending upon individual variations. Dosage 750 mg of Ascorbic acid and 490 mg of choline chlorine (approximately 350 mg of choline base) mixed in daily dosage of alcohol beverages. Every person consumed 490 ml of alcohol (10.0%) week, i.e. at the average of 70 ml/day of 100% pure alcohol. - All person belongs to the age group of 25-35 yrs. having a minimum of 2 years drinking habit - All persons were apparently healthy. - None of them had any other chronic liver disease or received any liver treatment in the recent past. - No person has muscle injury. Before actual test trial a 6 weeks conditioning phase was arranged wherein all 8 people were divided in two groups. Control and test groups ingested the equal amounts of alcohol per week up to 135 days. - Control group received a placebo mixed liquor for next 135 days while - Test group received composition added Uquor for next 135 days. Control group showed no significant chances in selected parameters. - Samples were drawn in the morning with person seated for 10-15 minutes - No considerable change in body weight observed before and after the test phase in any subject. Study was completed without any adverse drug reaction. No person showed significant weight gain. Serum levels of AST, ALT, GGT were estimated at 0, and 6 week interval. MCV, BP and Lipid profile were tested at 0 and 135 days. Table 1:0 - 6 weeks time frame of treatment (Table Removed) Table 2: After 135 days (Table Removed) * indicates ratio The ingestion of the composition of the invention substantially reduces and in fact halts the progression of hepatic damage. Other problems associated with prolonged alcohol abuse such as peptic ulcers, depression, and the like can also be reversed. The composition also substantially reduces lipid deposition in lipid profile. Clinical trials have confirmed that the composition of the invention resulted in reduction of hepatic damage in terms of liver steatosis, lipid formation, and increase in liver density. It was also observed that significant absorption of the composition occurred in the intestine and that large amounts of the ingested composition were localized in the liver. Choline chloride was converted by methylation and therefore increased the phospholipid metabolism in the liver. The composition can be administered as such or with conventional excipients. The composition can also be administered in liquid form, suspension or a solid form such as a tablet or powder. The composition can also be administered in encapsulated form, with the encapsulating material being any pharmacologically acceptable encapsulating agent. The additive composition of the invention can also be administered in pre-mixed form with alcohol, the additive being added at the time of bottling. The composition of the invention is a synergistic composition with improved and unexpected properties and not a mere aggregation of the properties of the individual ingredients. It must also be realized that various modifications are possible within the scope of the present invention, and that the above disclosure should therefore not be construed as limiting in any sense. We claim: 1. A composition for use as an additive in alcohol for human consumption and is useful in ameliorating the effect of alcohol on the human system, said composition comprising a mixture of a choline compound and ascorbic acid, the choline compound being present in an amount of 50 mg to 3000 mg and the ascorbic acid being present in an amount of 50 mg to 4000mg per 70 ml of 100% alcohol. 2. A composition as claimed in claim 1 wherein the choline compound comprises choline chloride. 3. A composition as claimed in claim 1 wherein the amount of choline chloride in the composition is 490 mg and the amount of ascorbic acid is 750 mg, both amounts being in based on 70 ml of 100% alcohol. 4. An alcohol formulation comprising a combination of alcohol for human consumption and an additive composition, and wherein for every 70ml of 100% alcohol, the additive composition comprises a mixture of a choline compound and ascorbic acid, the choline compound being present in an amount of 50 mg to 3000 mg and the ascorbic acid being present in an amount of 50 mg to 4000mg. 5. An alcohol formulation as claimed in claim 4 wherein the choline compound comprises choline chloride. 6. An alcohol formulation as claimed in claim 4 wherein the amount of choline chloride in the composition is 490 mg and the amount of ascorbic acid is 750 mg, both amounts being in based on 70 ml of 100% alcohol. 7. An alcohol formulation as claimed in claim 4 wherein the alcohol component can be any alcohol intended and legally sold or distributed for human consumption such as for example the group consisting of whisky of any kind, toddy, rum, beer, gin, vodka, wine of any type, and brandy, medicinal alcohol, cognac, port, sherry, rice wine, sake, liqueurs, schnapps, country liquors, and the like. 8. An additive composition for alcohol for human consumption substantially as described hereinbefore and with reference to the foregoing examples. 9. An alcohol formulation substantially as described hereinbefore and with reference to the foregoing examples.

Full Text

COMPOSITION FOR MODERATING EFFECT OF ALCOHOL ON HUMAN BODY Field of the invention
The present invention relates to a composition for moderating the effect of alcohol on a human body. More particularly, the present invention relates to a composition which is useful for moderating the intoxicating effect of alcohol consumption on a human body without requiring reduction in the level of alcohol consumption.
The present invention also relates to a process to increase plasma free choline level in a subject in order to prevent initial stages of liver steatosis. The present invention also relates to a composition for the reduction and/or prevention of liver steasosis in a subject.
The present invention also enables reduction of fatty tissue deposits and alcohol related liver degeneration. The present invention also relates to a composition which alter lipid metabolism and which possesses preventive effect on liver degeneration. Background of the invention and prior art
Alcohol consumption is known to cause serious damage to the human body. A heavy or even moderate drinker faces The health risks that a heavy drinker faces are obesity, addiction, ulcers, brain damage, liver cirrhosis etc. Also, the oxidation of fatty acid is impaired in the mitochondria. These fats accumulate in the liver to produce fatty liver. Alcohol can supply excess calories leading to weight gain.
Alcohol (all varieties which as such are legally sold and imbibed by human beings) is a depressant. Imbibing alcohol slows down the central nervous system
resulting therefore in a slower transmission of messages through the nerve fibers.
Among the effects of alcohol are a marked tendency, in the imbiber to become apparently relaxed, slurring of speech, slower reactions and reflexes, and varied mood swings. The above effects are attributable to the fact that alcohol replaced water molecules around the nerve cells, thereby interfering with the movement of electrically charged atoms, which are responsible for transmission of messages in the nervous system. Alcohol also slows down the movement of the chemical messenger molecules which carry information from cell to cell in the human body.
Lipotropic agents are substances that stimulate removal of excess fat from liver. Such substances include choline, inositol, methionine, Vitamin B12, folic acid etc. Studies suggest that choline be studied for treating fat disorder, hepatic degeneration, but never referenced in management of alcohol damage.
Choline deficiency has been known to cause fatty infiltration of liver, thus a deficiency in choline may result in the inability of the liver to transport fatty acid such as triglyceride. Study show that hepatic steatosis in many long term total parentral nutrition patients may be caused by a deficiency in plasma free choline and such deficiencies may be reversed by pharmacologically accepted salt of choline, that increases free choline and decreases hepatic steatosis.
It is known that choline by itself fails to prevent liver fibrosis in alcohol (ethanol) fed baboons and in fact causes toxicity [Leiber, et al, Hepatology 1985, Jul-Aug, 5(4), 561 - 572]. It is also reported that ethanol alone may affect hepatic one carbon metabolism, which requires the participation of both methionine and choline in transfer of methyl groups [Trimble et al, Hepatology, 1993,18(4), 984 - 989].
The effect of concomitant use of choline salt along with alcohol consumption
on reducing the after effects of alcohol consumption was gone unnoticed. The prior
art does not suggest or teach the use of controlling after effects of consumption of alcohol using choline by itself or in synergistic combination with another substance. The use of choline to treat fatty liver and alcoholic in etiology has not proven to be consistently effective.
Acetyl choline is synthesized from choline and acetyl COA by acetyl choline transferase. Choline is transported between the brain and plasma by a bidirectional system localized in the endothelium of the brain capillaries. This system operates by facilitated diffusion and the amount of choline available to the central neurons in the nervous system thus varies as a function of the concentration of choline in plasma.
Conventionally, the needs of tissues for choline are met by both exogeneous (dietary) sources and endogeneous (metabolic) sources. Biosynthesis of choline occurs by transmethylation of ethanolamine with the methyl group of methionine or by a series of reactions requiring vitamin B12 and folate as cofactors. Due to the synthesis of choline from other methyl donors, provision of a well balanced diet is usually effective in alleviating the symptoms of hepatic damage.
However, what is observed in clinical practice is that heavy imbibers of alcohol also suffer from deficient diet. As a result hepatic damage due to imbibing of alcohol is not remedied by a balanced diet Since the availability of brain choline and brain acetylcholine depends on facilitated diffusion, it is important to ensure that optimum levels of plasma choline are present for optimum brain activity. Alcohol itself being a depleting agent of choline, results in brain dysfunction.
It is also observed that chronic alcohol abuse is also a significant cause for malnutrition, including vitamin and mineral deficiency, particularly of vitamins A,
Bl to B12 and C. Vitamin and mineral metabolism is disrupted due to liver damage
caused by long term alcohol abuse. Alcohol also has a diuretic effect as a result of the reduction of the amounts of vasopressin leading to further depletion of vitamins and minerals from the human body.
Vitamin C is a known anti-oxidant which protects all cells from oxidative damage and is also a proficient anti-carcinogenic nutrient. Vitamin C blocks the creation of the carcinogen nitrosamine. Objects of the invention
The main object of the invention is to provide a composition for use as an additive in alcohol intended for human consumption, which reduces or ameliorates the negative effect of alcohol consumption on the human body. Summary of the invention
Accordingly the present invention provides a composition for use as an additive in alcohol for human consumption and is useful in ameliorating the effect of alcohol on the human system, said composition comprising a mixture of a chloine compound and ascorbic acid, the choline compound being present in an amount of 50 mg to 3000 mg and the ascorbic acid being present in an amount of 50 mg to 4000mg per 70 ml of 100% alcohol.
In one embodiment of the invention, the choline compound comprises choline chloride.
In yet another embodiment of the invention, the amount of choline chloride in the composition is 490 mg and the amount of ascorbic acid is 750 mg, both amounts being in based on 70 ml of 100% alcohol.
The present invention also provides an alcohol formulation comprising a
combination of alcohol for human consumption and an additive composition, and
wherein for every 70ml of 100% alcohol, the additive composition comprises a mixture of a choline compound and ascorbic acid, the choline compound being present in an amount of 50 mg to 3000 mg and the ascorbic acid being present in an amount of 50 mg to 4000mg.
In one embodiment of the invention, the choline compound comprises choline chloride.
In yet another embodiment of the invention, the amount of choline chloride in the composition is 490 mg and the amount of ascorbic acid is 750 mg, both amounts being in based on 70 ml of 100% alcohol.
In another embodiment of the invention, the alcohol component can be any alcohol intended and legally sold or distributed for human consumption such as for example the group consisting of whisky of any kind, toddy, rum, beer, gin, vodka, wine of any type, and brandy, medicinal alcohol, cognac, port, sherry, rice wine, sake, liqueurs, schnapps and the like.
The compositions of the invention are synergistic admixtures showing improved and unexpected properties over the aggregate properties of the individual ingredients and are not a mere aggregation of the properties of the ingredients. Detailed description of the invention
A composition is provided in accordance with the invention which comprises
essentially of a combination of Vitamin C and choline chloride. The interaction
between choline chloride and Vitamin C has several beneficent effects on alcohol
abuse induced problems on the human body. For example, the composition of the
invention serves to replenish the choline levels in the brain thereby repairing the
brain dysfunction that occurs on imbibing alcohol. In addition, vitamin C functions
also as a regular nutrient replenishing the vitamin levels in the body. These however are merely known properties of the two ingredients of the composition.
More importantly, choline chloride and vitamin C act synergistically to ensure that hepatic damage to the liver in terms of liver steatosis is prevented/minimized. This can be ascribed to the interaction between choline chloride and Vitamin C whereby the anti-oxidant nature of vitamin C is enhanced, due to the participation of ascorbate in oxido-reducing process connected with ethanol metabolism. Another significant advantage is that the composition of the invention can be administered along with the alcohol itself, without impairing any sensory pleasure that the imbiber obtains on imbibing alcohol.
It has now been observed after detailed clinical trials that a mixture of a choline compound such as choline chloride and ascorbic acid exhibit a surprising effect in alleviating the metabolic disturbances caused by alcohol particularly increase in Blood pressure, mean corpuscular volume (mcv), lipid content in circulation and most important increased liver enzymes. These effects are quite surprisingly particularly in the view of the fact that such effects are not observed when administering either choline chloride or ascorbic acid alone. Thus according to the present invention choline chloride and ascorbic acid must be used in combination.
Source of choline in diet tend to be found in high fat, high cholesterol food such as meat, liver, egg, which should be avoided by the alcohol drinker and person with compromised liver and person who tends to be obese. Therefore pursuant to the present invention additional choline variant is preferably ingested orally.
Choline variant is a compound currently approved for human use.
For alleviation of the result of drinking, the choline variant is preferably concomitantly administered with the drinking. Ideal dose may vary according to amount of alcohol consumption. The effectiveness of composition in alleviation of alcohol abuse and liver necrosis concerning alcohol consumption has been demonstrated herein.
The choline variant effective for the disclosed uses include any substance of which choline itself is a metabolite. Other choline variants with different substituent groups wold be expected to exhibit similar properties.
Choline chloride is administered in order to increase blood levels of choline and thereby to increase the level of acetylcholine in the brain. Administration result in desirable behavioral modification and in alleviation of psychogenic and nervous symptomatology associated with alcohol abuse. Most commonly associated psycholenic symptoms of alcohol abuse comprises anxiety, depression, decreased cognition, hostility and violence.
Technically alcohol is referred as a depressant, that is it slows down the activity of central nervous system, so that messages take longer to travel along nerve fibers. An alcohol consumer becomes slower in movement and speech becomes slurred.
The amount of choline available to central neurons varies as a function of the concentration of choline in plasma. When choline chloride is given, a sequential increase in the concentration of plasma choline, brain choline and brain acetylcholine is expected.
The need of the tissue for choline are met from both exogenous (=dietary) and
endogenous source. Biosynthesis of choline occurs by transmethylation of
ethanolamine with the methyl group of methionine or by a series of reactions requiring vitamin B12 and foliate as cofactors. Thus and adequate supply of methyl group donors in diet is desirable, to protect against the hepatic accumulation of lipid. Because of synthesis of choline from other methyl donors, provision of well-balanced diet is just as effective in alleviating the symptoms of hepatic damage. Available facts support the conclusion that the synthesis of choline is not always sufficient to meet human requirement of choline.
Chronic alcohol abuse is a significant cause of malnutrition including vitamin and mineral deficiency, particularly B6, B12 and C. Alcohol has a large energy content, so those who drink a lot, often eat less food, thereby increasing the risk of vitamin and mineral deficiency. Alcohol has a diuretic effect by reducing the amount of vasopressin which leads to many vitamins and minerals being flushed out of body. At the same time alcohol blocks the uptake of vitamin and mineral by irritating the mucous membrane of alimentary canal. The need for the nutrients is increased, because the alcohol causes tissue damage, which then needs repair. Additional supply of choline chloride can help in repairing the tissue damage by intermediary metabolism.
The consumption of alcohol also results in the formation of two very toxic
compounds - acetaldehyde and malondialdehyde. These compounds generate
massive free radical damage to cells throughout the body. The free radical damage
generated by this alcohol metabolite creates an effect in the body similar to radiation
poisoning, resulting in people feeling sick the day after consuming too much alcohol.
The composition of the invention helps to reduce the concentration of aldehyde. It is
believed that this occurs due to the interaction of the composition of the invention in
oxido reducing process, as a result of which the mitochondria remain healthy and clear the aldehyde at faster and better rate. The beneficial effects could also be due to reduced aldehyde concentration thereby limiting structural damage to liver cell and restores better mitochondria function. Another potential reason could be the reduction in hepatic cell necrosis which can be interpreted by liver enzyme, AST/ALT/GGT and the like. Healthy hepatocytes also favour reduction in concentration of aldehydes. The additive composition of the invention provides liver protection by altering the alcohol metabolism in the body by enhancing the aldehyde clearance by mitochondria thereby reducing the aldehyde concentration.
The improved oxido reducing process due to composition of the invention results in the mitochondria clearing the acetaldehyde at better efficiency and resulting in reduced aldehyde concentration in body tissue in alcoholics. This results in restricted hepatic cell necrosis due to aldehyde that is manifested by reduced level of liver enzymes. Increased systolic B.C. is another complication supposed to be related with hepatic damage due to aldehyde in alcoholics. Efficacy of composition of the invention to improve the oxidative metabolism were confirmed by test result data of serum cholesterol to high density lipid (HDL) ratio of the subjects indicated in the Table 2 below. Lipid oxidation shifts towards the healthier side, and at the same time reduced mcv also support the fact of improvement of lipid oxidative metabolism.
Other subjects treated with higher doses of content of composition showed improvement in depression, memory impairment and muscular co-ordination generally encountered in alcoholics. Few subjects of the same group also reported no
sluggish liver on the next day of drinking and countable improvement on gastric
ulcer if were present. The composition of the invention can also be used in encapsulated form with conventional encapsulates.
As a consequence of the hepatic metabolism of alcohol a series of metabolic alteration take place, which are responsible for liver damage. Metabolism in the hepatocyte:
There are three systems, which are able to metabolise ethanol - ADH - alcohol dehydrogenase, the microsomal ethanol oxidising system (MEOS) and catalase. Each of these lead to acetaldehyde production, being acetaldehyde the toxic metabolite and ethanol. In second step acetaldehyde is metabolised to acetate by mitochondria. Acetate produced in liver are released in to blood and oxidation to CO2, fatty acids and water. Metabolic changes:
During ethanol oxidation hydrogen is transferred from the substrate to cofactor NAD, converting it to its reduced form NADH. The excess of reduced equivalents mainly NADH produces a change in redox system. The redox imbalance is responsible for the metabolic alterations, which favors liver damage. Increase in NDH/NAD favors the synthesis of fatty acid.
The mechanism by which fatty acids are accumulated in the liver in the form of tryglycerides is complex. Increased MEOS activity is produced as a consequence of chronic alcohol consumption and this affects the CYP2E1 (ethanol inducible fraction of the cytochromP450) which has a relative high redox potential leads to formation of free oxygen radical and oxidative stress. Acetaldehyde diminishes the activity of mitochondria to oxidise fatty acid as well as other functions. These
mitochondrial dysfunction leads to higher level of acetaldehyde in the plasma causing of damage.
Regular alcohol consumption causes significant reduction in mitochondrial capacity to oxidize acetaldehyde. This is due to lower capacity of mitochondria to deoxidize NADH.
The composition of the invention helps to revive the mitochondrial function and thereby helps to get back the normal ration of NADH/NAD that prevents the liver damages caused by alcohol intoxication.
Increased level of acetaldehyde due to alcohol consumption, lead to liver cell-necrosis, resulting in high levels of liver enzymes. The composition of the invention when added to liquor restores mitochondrial function thereby enabling the mitochondria to oxidize the acetaldehyde and reducing the concentration of acetaldehyde in blood, thereby preventing hepatic cell damage which result in the decreased level of liver enzymes i.e. AST/ALT/GGT. (As shown in table). Composition added liquor fights with oxidation stress also, which is generally caused by alcohol intoxication and protects the hepatocytes from another side. Blood Pressure (B.P.)
Elevated BP is a very common feature in alcohol users. Rise in BP is assumed due to direct toxic effect and hepatic damage due to alcohol and its metabolite. Composition added liquor restricts the hepatic damage to the liver and helps to get back the BP towards the normal limits, (see Table 2) MCV
Lipid changes in blood and toxic effects of alcohol and its metabolite may
cause the MCV to increase and a picture of macrocytosis is often encountered in
alcoholics. MCV value gets to normal, if person passes a period of minimum 135
days under test trial, (see table 2)
LIPID
Due to alcohol intoxication lipid starts to deposit in liver and so also the lipid content in blood circulation increases. Lipid profile disturbs and shifts to higher level of serum cholesterol and ratio of S. cholesterol/HDL (HDL = High Density Lipid) increases.
During the trial phase of composition added liquor, the contents of composition makes a fall in the ration of serum cholesterol/HDL. EXAMPLE
Dose related may vary in different persons depending upon individual variations. Dosage
750 mg of Ascorbic acid and 490 mg of choline chlorine (approximately 350 mg of choline base) mixed in daily dosage of alcohol beverages. Every person consumed 490 ml of alcohol (10.0%) week, i.e. at the average of 70 ml/day of 100% pure alcohol.
- All person belongs to the age group of 25-35 yrs. having a minimum of 2 years drinking habit
- All persons were apparently healthy.
- None of them had any other chronic liver disease or received any liver treatment in the recent past.
- No person has muscle injury.
Before actual test trial a 6 weeks conditioning phase was arranged wherein all 8 people were divided in two groups. Control and test groups ingested the equal amounts of alcohol per week up to 135 days.
- Control group received a placebo mixed liquor for next 135 days while
- Test group received composition added Uquor for next 135 days. Control group showed no significant chances in selected parameters.
- Samples were drawn in the morning with person seated for 10-15 minutes
- No considerable change in body weight observed before and after the test phase in any subject.
Study was completed without any adverse drug reaction. No person showed significant weight gain. Serum levels of AST, ALT, GGT were estimated at 0, and 6 week interval. MCV, BP and Lipid profile were tested at 0 and 135 days.
Table 1:0 - 6 weeks time frame of treatment

(Table Removed)
Table 2: After 135 days

(Table Removed)
* indicates ratio
The ingestion of the composition of the invention substantially reduces and in fact halts the progression of hepatic damage. Other problems associated with prolonged alcohol abuse such as peptic ulcers, depression, and the like can also be reversed. The composition also substantially reduces lipid deposition in lipid profile.
Clinical trials have confirmed that the composition of the invention resulted in reduction of hepatic damage in terms of liver steatosis, lipid formation, and increase in liver density.
It was also observed that significant absorption of the composition occurred in the intestine and that large amounts of the ingested composition were localized in the liver. Choline chloride was converted by methylation and therefore increased the phospholipid metabolism in the liver.
The composition can be administered as such or with conventional excipients. The composition can also be administered in liquid form, suspension or a solid form such as a tablet or powder. The composition can also be administered in encapsulated form, with the encapsulating material being any pharmacologically acceptable encapsulating agent. The additive composition of the invention can also be administered in pre-mixed form with alcohol, the additive being added at the time of bottling.
The composition of the invention is a synergistic composition with improved and unexpected properties and not a mere aggregation of the properties of the individual ingredients.
It must also be realized that various modifications are possible within the scope of the present invention, and that the above disclosure should therefore not be
construed as limiting in any sense.

We claim:
1. A composition for use as an additive in alcohol for human consumption and is useful in ameliorating the effect of alcohol on the human system, said composition comprising a mixture of a choline compound and ascorbic acid, the choline compound being present in an amount of 50 mg to 3000 mg and the ascorbic acid being present in an amount of 50 mg to 4000mg per 70 ml of 100% alcohol.
2. A composition as claimed in claim 1 wherein the choline compound comprises choline chloride.
3. A composition as claimed in claim 1 wherein the amount of choline chloride in the composition is 490 mg and the amount of ascorbic acid is 750 mg, both amounts being in based on 70 ml of 100% alcohol.
4. An alcohol formulation comprising a combination of alcohol for human consumption and an additive composition, and wherein for every 70ml of 100% alcohol, the additive composition comprises a mixture of a choline compound and ascorbic acid, the choline compound being present in an amount of 50 mg to 3000 mg and the ascorbic acid being present in an amount of 50 mg to 4000mg.
5. An alcohol formulation as claimed in claim 4 wherein the choline compound comprises choline chloride.
6. An alcohol formulation as claimed in claim 4 wherein the amount of choline chloride in the composition is 490 mg and the amount of ascorbic acid is 750 mg, both amounts being in based on 70 ml of 100% alcohol.
7. An alcohol formulation as claimed in claim 4 wherein the alcohol component can be any alcohol intended and legally sold or distributed for human consumption
such as for example the group consisting of whisky of any kind, toddy, rum, beer, gin, vodka, wine of any type, and brandy, medicinal alcohol, cognac, port, sherry, rice wine, sake, liqueurs, schnapps, country liquors, and the like.
8. An additive composition for alcohol for human consumption substantially as described hereinbefore and with reference to the foregoing examples.
9. An alcohol formulation substantially as described hereinbefore and with reference to the foregoing examples.

Documents:

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Patent Number

268554

Indian Patent Application Number

576/DEL/2003

PG Journal Number

36/2015

Publication Date

04-Sep-2015

Grant Date

03-Sep-2015

Date of Filing

07-Apr-2003

Name of Patentee

PAWAN KUMAR VERMA

Applicant Address

554/37/4G/11A, PAWAN PURI, ALAMBAGH, LUCKNOW-226 005, U.P

Inventors:

#	Inventor's Name	Inventor's Address
1	PAWAN KUMAR VERMA	554/37/4G/11A, PAWAN PURI, ALAMBAGH, LUCKNOW-226 005, U.P

PCT International Classification Number

A61K 35/78

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA