FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
&
PATENTS RULES, 2003
(COMPLETE SPECIFICATION)
TITLE OF THE INVENTION- "SYNERGISTIC COMPACT ORAL FORMULATION FOR HEPATIC DISEASES, OSTEOARTHRITIS, CARDIOVASCULAR AND NEUROLOGICAL DISORDERS."
NAME OF APPLICANT- ZOTA HEALTH CARE LTD
ADDRESS OF APPLICANT- ZOTA HEALTH CARE LTD
ZOTA HOUSE
2/896, HIRA MODI STREET, SAGRAMPURA SURAT 395002 (GUJARAT) INDIA.
The following specification particularly describes the nature of the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION- The present invention relates to efficient oral pharmaceutical composition which comprises main active ingredients such as taurine and S-adenosylmethionine along with some pharmaceutically acceptable excipients preferably in oral dosage form.
BACKGROUND OF THE INVENTION
Liver is the largest organ inside the body. It is also one of the most important. The liver has many jobs, including changing food into energy and cleaning alcohol and poisons from the blood. The liver also makes bile, a yellowish-green liquid that helps with digestion.
There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, hepatitis B and hepatitis C. Others can be the result of drugs, poisons or drinking too much alcohol. If the liver forms scar tissue because of an illness, it's called cirrhosis. Jaundice, or yellowing of the skin, can be one sign of liver disease.
According to US Patent 5906811 wherein said The combination of several synergistic antioxidants, enzymatic co-factors and amino acids in appropriate delivery vehicles employed in aerosol carriers, mist and pump oral sprays, solutions, such as oral irrigators, mouth rinses and mouthwashes, or gels and solid compositions as a means of preventing and ameliorating signs and symptoms and complications to the oro-pharyngeal cavity and mouth including buccal mucosa, gums and tongue and the upper respiratory tract from damage caused by free radical species induced by tobacco smoke, smokeless tobacco, ingested or chewed noxious, malodorous or harmful substances and other inhaled environmental pollutants and particulate matter, including tobacco to secondary smokers.
According to United States Patent 5817695 wherein said A nutritional product is provided for cancer patients comprising, as per caloric requirement, a low concentration of carbohydrate, a high concentration of fat and an imbalance of amino acids wherein L-phenylalanine, L-tyrosine and L-methionine are present in the below normal concentrations and L-leucine is present in substantial excess of normal concentrations to suppress cancer growth and as an adjunct to conventional cancer therapies
According to European Patent EP1408988 wherein said provided is a synergistic combination of nutritional supplements classified as Nutraceuticals and further combined with antioxidant vitamins and minerals that, when orally administered to mammals, provides optimal delivery

of vital metabolic precursors necessary for the production and repair of articular cartilage. Specifically provided is a unique combination of chondroitin sulfate sodium, methylsulfonylmethane, glucosamine potassium, glucosamine hydrochloride, glucosamine sulfate sodium, N-acetyl D-Glucosamine, sodium absorbate and chelated manganese proteinate compounded through agitation. The provided compositions and methods of administration are designed to effectively elevate and sustain blood levels of said compounds in turn enhancing the body's natural chondroprotective mechanisms while providing an efficient delivery mechanism which optimizes cellular uptake of glucosamine and chondroitin. This process of forming specified synergistic relationships between vital metabolic precursors increases the body's production of proteoglycans, chondrocytes, hyalauron glycosaminoglycans and collagen, facilitating the repair and regeneration of articular cartilage and symptomatic relief from pain and inflammation associated with articular degeneration.
According to WO 2006/062273 Al, wherein said the present invention relates to a health supplement food utilizing, in particular, branched amino acids from among essential amino acids. More specifically, the present invention relates to: a health supplement food comprising branched chain amino acids (herein after, referred to as LIV) composed of leucine (L), isoleucine (I) and valine (V) which is made to have a composition similar to essential amino acids contained in naturally-occurring milk, eggs, soybeans, beef and the like, and enhancing instant impact power under anaerobic conditions, via addition of L- glutamine and taurine which are essentially required when a person is exposed to excessive exercise, stress or overwork; a health supplement food for improving a weak constitution, comprising herbal materials such as ginseng, red ginseng and Acanthopanax; and a diet food or beverage further comprising dietary fibres such as insulin, polydextrose and crystalline cellulose, and carnitine and hydroxy citric acid.
According to WO 2007/115112 A2wherein said an exemplary dried, meat-based product includes meat and plant seed where the plant seed comprises at least approximately 3% caffeine by weight. For example, an exemplary product includes guarana plant seed. According to various products and processes, plant seed may be provided as a powder
According to US 2009/0005320 Al wherein said The invention relates to compositions comprising one or more ionic salts, each of said ionic salts consisting of a bicarbonate anion

and a cation selected from the group consisting of an amino acid, an amino acid derivative, a di-peptide and a tri-peptide, and to methods of making and using said compositions.
Certain amino acids have found to play a promising role in preventing and treating a majority of these liver diseases due to their antitoxic and antioxidant properties. Racemethionine and Taurine are vital amongst them.
SUMMARY OF THE INVENTION
In one aspect, the invention is to provide commercially viable and efficient formulation.
In one aspect, the invention is to provide safe and effective dosage form with taurine and S-adenosyl methionine and other ingredients
In one aspect, the invention is to provide different release drug profile such as Sustained or controlled or retard formulation available in oral formulation (capsule, tablet, powder thereof)
In one aspect, it will provide instant energy and work like prophylactic total health care.

DETAILED DESCRIPTION OF THE INVENTION
The invention will now be described in detail in connection with certain preferred and optional embodiments. So that various aspects thereof may be more fully understood and appreciated.
The present invention discloses an efficient pharmaceutical composition in oral dosage form. This comprises therapeutically effective amount of taurine, S-adenosylmethionine thereof so as to make the formulation stable.
According to the oral pharmaceutical composition of the present invention, the said oral pharmaceutical composition is available in various forms such as tablet, capsule, sachet, powder, liquid thereof. It is useful supplementation in patients suffering from liver diseases and may also provide valuable benefits in patients suffering from cardiovascular diseases, neurological disorders and others.
In embodiment of the invention, Taurine, a liver protecting amino acid, It is essential for formation of bile acids and thus for detoxification processes, it reduces the secretion of apolipoprotein B100 and lipids in Hepatic G2 cells and is effective in removing fatty liver deposits, preventing liver disease, and reducing cirrhosis. Importantly taurine has protective and preventive role in portal hypertension, the major cause of death in cirrhotic liver conditions. It is useful in treating people with alcohol dependency and is a detoxifying agent with antioxidant action that helps protect liver cells against various toxins.
In the case of liver health wherein Taurine is known that the iiver is the main organ for taurine biosynthesis and also an important target organ for taurine's many biological activities. It is essential for formation of bile acids and thus for detoxification processes.
Taurine plays following important roles in hepatoprotection -
-It Combines and removes of toxic chemicals and metabolites.
-Antioxidant action
-Taurine increases levels of antioxidant enzymes like glutathione peroxidase, superoxide dismutase and catalase in liver and thus protects hepatocytes from free radical and ROS induced damages

-As essential component of cell membranes wherein it enhances transport of important ions across hepatocytes thus improving their functions and recovery. A deficiency of taurine can lead to electrolyte imbalance due to impaired mineral transport across cell membranes and this reduces the ability of the liver to remove toxic substances.
The inclusion of taurine in a liver supplementation is beneficial for the above reasons.
In the case of Taurine deficiency and liver injuries (study on mice) wherein Taurine deficiency can trigger hepatitis and liver fibrosis, probably due to a diminished antioxidant defence, increase in inflammatory reactions and mitochondrial dysfunction in hepatocytes.
Taurine deficiency increases free radicals ROS mediated oxidative damages and formation of toxic metabolites in liver cells. This can be seen as there is a 6-fold increase in the TNF plasma levels. Tissue necotising factor alpha is a marker for inflammatory processes that leads to cell death. Taurine supplementation prevents these damages and protects cells.
Severe toxicities cause death of more and more hepatocytes. These cells are replaced by formation of new cells. If the cell destruction is high, the newly formed cells are immature and abnormal in shape (oval shape). Development of these cells is associated with liver dysfunction.
Taurine protects liver tissue from necrosis (cell death), inflammation, and fibrosis, and helps protect cells from damage.
This effect is observed in a rat study which used carbon tetrachloride as toxicant. Taurine pre-treatment induced a marked beneficial effect regarding the prevention of hepatocellular necrosis and atrophy as demonstrated morphologically. In conclusion, these results suggest that taurine pre-treatment prevents the morphologic damage caused by CCI4 in the early stages.
Further taurine helps for normal hepatocyte structures and prevents formation of extracellular matrix which otherwise leads to liver fibrosis.
Taurine in alcoholic liver disorders wherein Taurine reverses the hepatic steatosis (deposition of fat) and lipid peroxidation caused by chronic alcohol consumption in rats

As per clinical study, Taurine has been shown to be useful in treating people with alcohol dependency involving over 3,000 alcohol dependent people who were given taurine showed that taurine is more effective than placebo at preventing alcohol relapse.
Taurine increases urine excretion of homocysteine during alcohol withdrawal. Rise in blood homocysteine (hyperhomocysteinaemia) was observed in chronic alcoholics who underwent withdrawal from alcohol. Homocysteine has excitatory effects in brain and is associated with nervous restlessness and other psychotic episodes seen during alcohol withdrawal. Taurine being an inhibitory neurotransmitter reduces excitatory signals. It also reduces hyperhomocysteinaemia by excreting homocysteine through kidneys. This dual effect helps in alcohol withdrawal.
Twenty-two patients undergoing treatment for alcohol withdrawal were given 1 gram of taurine three times per day orally for seven days. When compared to retrospective controls, significantly fewer of the taurine-treated patients had psychotic episodes (14% vs. 45%, p < 0.05). The number of psychotic cases after admission who had also been psychotic before admission was 1/16 for the taurine group and 11/17 for the controls (p < 0.001).
The inhibitory amino acid taurine may constitute an important protective mechanism against excitotoxicity and thus protects against neuronal damage.
In embodiment of the invention, the major source of other liver detoxificants such as glutathione and S-Adenosyl Methionine (SAMe),
In embodiment of the invention, SAMe is an active compound made from methionine and adenosine triphosphate (ATP). It acts as a methyl donor in a variety of biochemical pathways. Methylation reactions are essential for the detoxification of harmful products of metabolism, and the synthesis of numerous physiological agents including neurotransmitters, cartilage, and glutathione. The role of SAMe for intrahepatic cholestasis associated with liver disease has been observed.
In the case of liver protection wherein SAMe improves and normalizes liver function. SAMe is used in the treatment of cirrhosis and liver damage caused by alcohol. Through methylation, SAMe increases membrane fluidity, restoring several factors that promote bile flow. Treatment with SAMe helps decrease serum bilirubin {pigment in the blood that can cause jaundice) in patients with elevated serum bilirubin level.

In the case of alcoholic liver disorder wherein SAMe is to be useful therapeutically in alcoholic liver injury including cholestasis, and in the devastating consequences of excessive liver fibrosis (leading to cirrhosis).
S-Adenosyl-L-methionine (SAMe) exerts major key functions in the liver, including serving as a precursor for cysteine and glutathion. SAMe is particularly important in opposing the toxicity of free oxygen radicals generated by various pathogens, including alcohol, which causes oxidative stress largely by the induction of cytochrome P4502E1 (CYP2E1) and by its metabolite acetaldehyde. SAMe also acts as the main methylating agent in the liver.
SAMe in vivo is associated with beneficial effects on liver function and structure and resulted in a corresponding attenuation of ethanol-induced liver injury as shown by less-striking glutathione depletion and lesser increases in plasma aspartate transaminase. SAMe also shows hepatocyte mitochondrial protection. As per the observation on rats, SAMe decreased ethanol-induced fat accumulation. Thus, SAMe was shown to be useful for opposing the oxidative stress and the alcohol-induced liver injury.
It contains methionine which has Methyl (-CH3) donor important in metabolic processes where methyl group is transferred to other compound (methylation). A precursor to other important substances like S-adenosyl methionine (SAMe), glutathione and amino acids like taurine and cysteine. Methionine levels determine the liver's concentration of sulfur-containing antioxidant compounds like SAMe and glutathione which improve and normalize liver functions. Methionine itself has a protective effect on glutathione and prevents depletion during toxic overload, which can protect the liver from the damaging effects of toxic compounds. Methionine residues on the surface of proteins (like enzymes) offer antioxidant protection and thus prevent degradation of proteins by reactive oxygen species and free radicals. Liver contains maximum amounts of enzymes and thus methionine concentration in liver is important for protection against toxic free radicals.
In the case of Liver protection wherein Cells in the liver and kidneys especially need methionine for regeneration. It helps in protection against the destruction of delicate liver tissues. Methionine helps maintain the health of the liver by removing toxins and giving protection.

In embodiment of the invention, L-cysteine, or N-acetyl-L-cysteine, or NAC, is the supplement form of cysteine, an amino acid. Amino acids are building blocks of protein and are found throughout the body. Your body converts the dietary supplement into cysteine, and then into glutathione, an effective antioxidant that fights free radicals in the body. L-cysteine is an important protein and a deficiency could cause serious health problems. L-cysteine is commonly used to help prevent major organ damage that can be caused by taking acetaminophen. In certain dietary supplement form, L-cysteine counteracts the mild pain reliever and its effects on the liver.
In embodiment of the invention, the liver produces glutathione. A deficiency of hepatic GSH and other antioxidants and/or an increase in oxidative stress, may contribute to the progression of liver disease. Glutathione is important in the management of patients with alcoholic liver disease and viral hepatitis, particularly those with hepatitis C. When individuals are fighting a chronic liver disease, their bodies utilize a compound known as glutathione. This powerful antioxidant helps detoxify the liver cells. With increased stress on the body, the levels of glutathione begin to decline. Glutathione also helps neutralize molecules called free radicals that can cause damage and death to cells if they are not kept under control.
Glutathione protects cells in several ways. It neutralizes oxygen molecules (free radicals) before they can harm cells. Together with selenium, it forms the enzyme glutathione peroxidase, which neutralizes hydrogen peroxide. It is also a component of another antioxidant enzyme, glutathione-S-transferase which is a broad-spectrum liver-detoxifying enzyme.
Glutathione protects the body from free radical damages as it contains Sulphur donating amino acid- Cysteine (formed from methionine) which helps to destroy harmful toxic materials from the body. Cysteine also functions as an effective binder of harmful heavy metals in the body, the depletion of Cysteine -an essential part of Glutathione can result in frequent sicknesses and damages to the liver.
Glutathione has several health benefits. Optimal amounts of glutathione are necessary for supporting the immune system, and, in particular, glutathione is required for replication of the lymphocyte immune cells. Glutathione also helps the liver to detoxify chemicals, such as acetaminophen, copper, and cadmium.

Glutathione protects not only individual cells but also the tissues of the arteries, brain, heart, immune cells, kidneys, lenses of the eyes, liver, lungs, and skin against oxidant damage. It plays a role in preventing cancer, especially liver cancer, and may also have an anti-aging effect.
Glutathione conjugation is an important step in detoxification process that produces water-soluble substances which are excreted via the kidneys. The elimination of fat-soluble compounds, especially heavy metals like mercury and lead, is dependent upon adequate levels of glutathione, which in turn is dependent upon adequate levels of methionine and cysteine. When increased levels of toxic compounds are present, more methionine is utilized for cysteine and glutathione synthesis. Methionine and cysteine have a protective effect on glutathione and prevent depletion during toxic overload. This, in turn, protects the liver from the damaging effects of toxic compounds and promotes their elimination.
In the case of Alcoholic liver disorder wherein Alcohol is a major cause of liver disease and disrupts methionine and oxidative balances.
As per the clinical trials on rats following steps obtained
In a study, a striking effect of free methionine consumption on histological liver injury, triglyceride accumulation, and energy-rich nucleoside content in the liver of rats with a jejunoileal bypass is demonstrated.
Methionine was found to strongly improve the alcohol-induced histological changes in the liver. Triglyceride content of the liver was found to decrease in a dose-dependent manner with increasing methionine ingestion.
Hepatic adenosine triphosphate content increased significantly with higher methionine consumption.
These results underscore the impairment of the transmethylation/transsulfuration pathway in the development of alcohol-induced liver diseases.
Due to above observation, its clarify that Methionine is the precursor for other important antioxidant substances like SAMe and glutathione.
Membrane alterations are common in alcoholic liver injury and are also associated with a decrease in phosphatidylcholine, the backbone of the membranes. SAMe increases

phosphatidylcholine concentrations in the liver membranes by methylation reactions and thus protects hepatocytes from damages.
Oxidative stress was shown to play a major pathogenic role in multiple disease states ranging from the hepatotoxicity of alcohol to the carcinogenicity of many compounds. The major natural defence mechanism against oxidative stress is reduced by glutathione, which traps the excess of free radicals. The most important role of Glutathione in alcoholic liver disorders is following:
The microsomal ethanol-oxidizing system has been the subject of extensive research. A 4-fold induction of cytochrome P4502E1 (CYP2E1) was found in liver biopsy samples from recently alcohol drinking subjects. CYP2E1 activates some xenobiotics (such as acetaminophen) to toxic metabolites. It also generates several species of active oxygen species. Glutathione provides one of the cell's fundamental mechanisms for the scavenging of toxic free radicals.
Alcohol causes liver disease through a variety of pathogenic mechanisms. The major mechanisms include interactions with nutrition and toxic manifestations through generation of oxidative stress and production of the toxic metabolite acetaldehyde.
The combination of SAMe and taurine shows a synergistic effect on targeted diseases.
Both SAMe and taurine are concentrated in liver and plays an important role in liver function, detoxification of harmful substances and hepatocyte protection. Many of their functions are independent of each other.
When taurine is used up for metabolic reactions, it is biosynthesized from methionine. Thus methionine is used up in this process. During stressed conditions or increased liver function requirements more and more methionine may be used up for taurine formation causing methionine depletion. Supplementation of taurine reduces the need for conversion of methionine to taurine thus allowing methionine for its other important functions especially for the liver protection, Osteoarthritis, cardiovascular and neurological disorder thereof.
Further, in some patients excess methionine has been reported to increase homocysteine levels. Increased homocysteine levels may be associated with abnormal cardiovascular

functions. It is found that taurine causes excretion of homocysteine via kidney and thus prevents its damages, if any.
Thus the combination of SAMe and Taurine is a synergistic combination useful in various liver diseases and others.
Thus according to preferred aspect, oral pharmaceutical composition of the present invention comprising dietary supplements, for replacing a necessary substance not found in large enough quantities in the diet, Preventing or decreasing the risk of developing a disease or condition, Boosting the immune system and improving general health, Boosting energy levels, Improving mental or physical performance, Reducing symptoms of a disease or health condition.
EXAMPLES-

INGREDEIENT
S Example 1 Example
2 Example
3 Example 4 Example 5
SAMe 100 mg 200 mg 300 mg 400 mg 500 mg
Taurine 100 mg 200 mg 300 mg 400 mg 500 mg

INGREDEIENT
S Example 6
(prefera bly) Example
7 Example 8 Example 9 Example 10
SAMe 700 mg 700 mg 800 mg 900 mg 1200 mg
Taurine 600 mg 700 mg 800 mg 900 mg 1000 mg

CLAIMS, We claim,
1. An efficient oral formulation comprises two or more active ingredients such as taurine and S-Adenosyl Methionine (SAMe) along with pharmaceutical acceptable excipients.
2. An efficient oral formulation as claimed in claim 1 wherein it is available in various forms such as tablet, capsule, sachet, powder and liquid thereof.
3. An efficient oral formulation as claimed in claim 1 wherein S-Adenosyl Methionine (SAMe) is a lipotropic amino acid in hepatoprotection. It is a potent methyl donor, powerful antioxidant and a major source of other liver detoxificants including glutathione and S-Adenosyl Methionine (SAMe).
4. An efficient oral formulation as claimed in claim 3 wherein that Methionine is the precursor for other important antioxidant substances like SAMe and glutathione.
5. An efficient oral formulation as claimed in claim 3 wherein the concentration of SAMe is 600 mg to 1200 mg , preferably 700 mg.
6. An efficient oral formulation as claimed in claim 3 wherein the concentration of taurine is 500mg to 1000 mg, preferably 600 mg.
7. An efficient oral formulation as claimed in claim 3 & 4 wherein SAMe improves and normalizes liver function. SAMe is used in the treatment of cirrhosis and liver damage caused by alcohol.
8. An efficient oral formulation as claimed in claim 1 wherein Taurine increases levels of antioxidant enzymes like glutathione peroxidase, superoxide dismutase and catalase in liver and thus protects hepatocytes from free radical and ROS induced damages.
9. An efficient oral formulation as claimed in claim 1 wherein both SAMe and Taurine are concentrated in liver and play important role in liver function, detoxification of harmful substances and hepatocyte protection. Many of their functions are independent of each other.

10. An efficient oral formulation as claimed in claim 1 wherein the end products such as L-cysteine, or N-acetyl-L-cysteine, or NAC, is the supplement form of cysteine (an amino acid) and glutathione, an effective antioxidant that fights free radicals in the body and protects liver , Osteoarthritis, cardiovascular and neurological disorder thereof.