Claims:We claim,

1. A polyherbal composition for liver support, the composition comprises:
a. an active constituent of root extract of Boerhaavia diffusa at a concentration of 12-15%, preferably 14.32%;
b. an entire plant of Phyllanthus niruri at a concentration of 10-15%, preferably 13.02%;
c. stem extract of Tinospora cordifolia at a concentration of 8-10%, preferably 9.11%;
d. an active constituent of root extract of Berberis aristata at a concentration of 5-8%, preferably 6.51%;
e. an active constituent of an entire plant of Andrographis paniculata, at a concentration of 5-8%, preferably 6.51%;
f. root extract of Capparis spinosa at a concentration of 5-8%, preferably 6.51%;
g. root extract of Cyperus rotundus at a concentration of 5-8%, preferably 6.51%;
h. fruit of Piper longum at a concentration of 0.5-1.5%, preferably 0.65%;
i. an active constituent of root extract of Picrorhiza kurroa at a concentration of 5-8%, preferably 6.51%; and
j. pharmaceutically acceptable excipients thereof at defined concentrations.

2. The polyherbal composition for liver support as claimed in Claim 1, wherein the active constituents of root extract of Picrorhiza kurroa comprises Picroside l and ll, an entire plant of Andrographis paniculata comprises Andrographolide, root extract of Berberis aristata comprises Berberine and root extract of Boerhaavia diffusa comprises Boeravinone-B.

3. The polyherbal composition for liver support as claimed in Claim 2, wherein the concentration of picroside l and ll is 5%, andrographolide is 0.5%, berberine is 0.5% and boeravinone-B is 0.1%.

4. The polyherbal composition for liver support as claimed in Claim 1, wherein the pharmaceutically acceptable excipients are selected from the group consisting of microcrystalline cellulose (MCC) at a concentration of 1.95%, crospovidone at a concentration of 4.94%, syloid 244 at a concentration of 0.97%, sodium starch glycolate at a concentration of 4.55%, magnesium stearate at a concentration of 0.97%, hydroxyl propyl methyl cellulose at a concentration of 1.82%, PEG 6000 at a concentration of 0.2%, titanium dioxide at a concentration of 0.032%, methylene chloride, iron oxide red at a concentration of 0.175% and iron oxide black at a concentration of 0.07%.
5. The polyherbal composition for liver support as claimed in Claim 1, wherein the polyherbal composition is formulated as one or more formulation selected from tablet, capsule, injectable solution, syrup, tincture, transdermal patch, nanofiber, dry powder inhaler and metered dose inhaler.
6. The polyherbal composition for liver support as claimed in Claim 1, wherein the polyherbal composition is effective in lowering the levels of elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum total bilirubin in liver disorder patients with abnormal liver function test (LFT).
7. A method (100) for preparing a polyherbal composition for liver support, comprising:
a. dispensing and sifting separately plurality of plant extracts including root extract of Boerhaavia diffusa at a concentration of 14.32%, an entire plant of Phyllanthus niruri at concentration of 13.02%, stem extract of Tinospora cordifolia at a concentration of 9.11%, root extract of Berberis aristata at a concentration of 6.51% , an entire plant of Andrographis panniculata at a concentration of 6.51%, root extract of Capparis spinosa at a concentration of 6.51%, root extract of Picrorhiza kurroa at a concentration of 6.51%, root extract of Cyperus rotundus at a concentration of 6.51% and fruit of Piper longum at a concentration of 0.65%, passing through mesh size 20 and collecting the said plant extracts in a separate double line polybag (102);
b. sifting pharmaceutically acceptable excipients selected from the group consisting of microcrystalline cellulose, crospovidone, sodium starch glycolate, sylloid 244 through mesh size 40 and magnesium stearate through mesh size 60 and collecting the said pharmaceutically acceptable excipients in separate double line polybag (104);
c. mixing the sifted plurality of plant extracts and pharmaceutically acceptable excipients in a Rapid Mixer Granulator (RMG) with impeller at slow speed and chopper off for 10 minutes and adding binder solution IPA to the obtained powder mixture in the RMG and mixing the said powdered mixture for 4 to 5 mins with impeller at slow speed and chopper off (106);
d. kneading the said powdered mixture for further 5 to 6 minutes with impeller at fast speed and chopper running at slow speed till end point of granule formation is observed and adding extra quantity of water if required (108);
e. drying the granules in fluid bed dryer at a temperature 40 to 450C till the granules achieves required Loss on Drying (LOD) and determining the LOD content by using IR moisture analyser at a limit of 3 to 4% w/w and at temperature of 1050C (110);
f. sifting the dried granules through mesh size 16 using vibratory sifter and passing the retained granules through 2.4 mm perforated stainless-steel screen on multi-mill with medium speed, knives forward and passing the milled granules through mesh size 16 and collecting the milled granules with the sifted granules in a stainless-steel bin (112);
g. transferring the sifted granules to a blender along with pharmaceutically acceptable excipients selected from the group consisting of crospovidone, sodium starch glycolate, microcrystalline cellulose (MCC), sylloid 244 for 10 minutes and adding magnesium stearate previously passed through mesh size 60 of step b and mixing for 3 minutes (114);
h. unloading the obtained lubricated blend and collecting the said lubricated blend in a double-line polybag (116);
i. compressing the said lubricated blend by using compression machine to form tablets; (118)
j. dispensing pharmaceutically acceptable excipients selected from the group consisting of polyethylene glycol, HPMC 6 CPS, titanium dioxide, purified talc, isopropyl alcohol, iron oxide red, iron oxide black and methylene chloride to make a coating solution to coat the obtained tablets (120); and
k. packing the said tablets in a HDPE bottle with proper quality of sealing and labelling (122).
, Description:Preamble to the Description
[0001] The following specification describes the invention and the manner in which it is to be performed:
DESCRIPTION OF THE INVENTION
Technical field of the invention
[0002] The present invention generally relates to a field of herbal medicines. In particular, the invention relates to a polyherbal composition for an effective management of various liver disorders. The present invention discloses a synergistic polyherbal composition possessing liver supporting formula, effective against various liver disorders such as hepatitis, non-alcoholic fatty liver disease, jaundice, alcoholic liver disease etc., and besides hepatoprotective activity against various hepatotoxins such as alcohol, drugs, viruses and chemicals.

Background of the invention
[0003] The liver is strategically located between the digestive tract and general circulation, plays a vital role in many bodily functions including, but not limited to, glucose homeostasis, digestion, cleansing, detoxification, protein production, blood clotting; cholesterol, fat and iron metabolism. There is a tremendous surge of liver related morbidity and mortality in recent years. A variety of illnesses can affect the liver apart from environmental factors. If untreated, in chronic liver disease the normal liver cells or hepatocytes are replaced by scar tissue, also called as cirrhosis with hardening and non-functionality of the organ. Symptoms of liver diseases include weakness and fatigue, weight loss, nausea, vomiting, discoloration of the conjunctivae (icterus), skin and nails (jaundice) and eventual death.
[0004] Diseases of the liver can be devastating, because no other organ in the body can compensate all these important functions. Alcohol, drugs, xenobiotics, and metabolites can damage liver cells and release aspartate aminotransferase (AST) and alanine aminotransferase (ALT) into blood circulation. The diagnostic indicators of liver diseases and injury include increase in serum AST and ALT, jaundice, increase in clotting times, edema, and hepatic encephalopathy. Many liver diseases impair liver metabolic functions and progress to nonalcoholic fatty liver disease (NAFLD), hepatic fibrosis, and cirrhosis.
[0005] Alcoholic liver disease is a major source of alcohol–related morbidity and mortality. Alcoholic Liver disease (ALD)/Alcoholic hepatitis is a syndrome of progressive inflammatory liver injury associated with long-term heavy intake of ethanol. The spectrum of alcohol-related liver injury varies from simple steatosis to cirrhosis. These are often grouped into three histological stages of ALD namely fatty liver or simple steatosis, alcoholic hepatitis, and chronic hepatitis with hepatic fibrosis or cirrhosis. Alcohol abstinence has a clear-cut mortality benefit and nutritional support is very important as most of the patients are malnourished and in a hypercatabolic state. Conventional therapy includes use of glucocorticoids and pentoxifylline. Liver transplantation improves survival in advanced alcoholic cirrhosis and it can be an option in severe alcoholic hepatitis patients who are not responding to other medical therapies.
[0006] Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of medical conditions in which there is increased infiltration of fat, predominantly triglycerides, inside hepatocytes. NAFLD is defined when there is macro vesicular steatosis inside liver cells exceeding 5% of liver weight, in the absence of significant ethanol consumption or other specific causes of liver diseases. Increased fat accumulation in liver or fatty liver disease can also be secondary to a number of causes, including excessive alcohol consumption, drugs (especially chemotherapeutic agents such as methotrexate, tamoxifen), hepatic toxins (e.g. arsenic, carbon tetrachloride), chronic viral hepatitis (e.g. hepatitis B and hepatitis C viral infection) and congenital storage diseases (e.g. Wilson disease, hemochromatosis). The prevalence of NAFLD in normal weight individuals without the presence of metabolic risk factors is reported to be around 16% rising to 60% in patients with diabetes, 91% in obese patients undergoing bariatric surgery, and up to 90% in patients with hyperlipidemia. Lifestyle intervention with diet and exercise are still the mainstay in the management of patient with NAFLD. Weight loss measures, insulin sensitizers (metformin), Lipid lowering and anti-hypertensive drugs, Vitamin E and anti-oxidants agents have effectively studied in the management of NAFLD.
[0007] Hepatitis A virus (HAV) and hepatitis E virus (HEV) both transmit enterically. HEV infection is responsible for 30%–70% of cases of acute sporadic hepatitis and is the major cause of acute liver failure (ALF). In India, hepatitis B virus (HBV) infection is of intermediate endemicity, with nearly 4% of the population being chronic HBV carriers, which is about 40 million people. The frequency of hepatitis C virus (HCV) infection, as evaluated by anti-HCV antibody positivity, has been reported to be 1%–2% among voluntary blood donors and 0.87% in the community. About 50% of chronic liver disease (CLD) is due to HBV and 20% is due to HCV infection. Hepatitis D virus (HDV) infection is found in fewer than 10% of patients with acute or chronic HBV infection.
[0008] HAV and HEV are usually self-limiting diseases, treatment is generally supportive. Interferon-a 2b, interferon-a 2a, pegylated interferons and nucleoside analogues such as lamivudine, adefovir, entecavir and tenofovir have been used to treat HBV infection. Combination therapy with pegylated interferon a 2b (1.5 mg/kg/ week) or a 2a (180 mg/week) with ribavirin (10.6 mg/kg/day) is recommended for patients with Chronic Hepatitis-C (CH-C) and compensated cirrhosis of the liver. The recommended duration of this treatment is 12 months for genotype 1 infection, and 6 months for genotype 2 or 3 infection. Interferon alfa is the only FDA-approved drug against HDV. Ribavirin, lamivudine, and other drugs are ineffective against HDV infection.
[0009] Furthermore, drugs are an important cause of liver injury. More than 900 drugs, toxins, and herbs have been reported to cause liver injury. The first line anti-tubercular drugs namely, Rifampicin, Isoniazid and Pyrazinamide are potentially hepatotoxic drugs. Atorvastatin-related hepatotoxicity has been associated with a mixed pattern of liver injury typically occurring several months after the initiation of the medication. Anti-rheumatic agents are among commonly used drugs associated with adverse hepatic reactions. Besides, nearly all of the NSAIDs have been implicated in causing liver injury. Therefore, the main treatment for drug induced hepatitis is discontinuation of the involved drug and specific treatments for drug induced hepatitis are scarce.
[0010] Day by day, researchers are identifying new and more powerful agents to prevent, treat, or retard infections and cure the diseases they cause. Billions of dollars are being spent every year in just identifying, locating, and developing these new drugs. However, till now effective therapies for many of the common disease such as liver, heart, kidney etc. are still elusive. Therefore, the existing therapies developed for various liver diseases are often limited in efficacy, carry the risk of adverse effects, and are often too costly, especially for the developing world. At present, most patients are treated with drugs that are very effective over a short term. However, they have very adverse effect on long term use. They are also very expensive and demonstrate many side effects and uncertain activities.
[0011] Due to the prevailing ill effects of existing drugs, the researchers are now focusing on plant-based drugs for the treatment of liver associated diseases. The herbal composition is effective in curing liver diseases in a very efficient manner without inducing any side effects.
[0012] The Japanese Application No. JP2006514975A titled “Synergistic hepatoprotective composition and method thereof” discloses a synergistic formulation for liver protection. A synergistic formulation comprising trans-tetracos-15-enoic acid (t-TCA) and andrographolide (AP) in a ratio ranging from 1: 7 to 7: 1 (w / w). In addition, the invention relates to a process for preparing a synergistic formulation useful for hepatoprotection comprising trans-tetracos-15-enoic acid (t-TCA) and andrographolide (AP), said process comprising t- Crushing TCA and AP particles into fine particles, mixing the fine particles in a ratio ranging from 1: 7 to 7: 1 (w / w), and crushing the mixture to obtain a formulation. Furthermore, the synergistic formulation comprising trans-tetracos-15-enoic acid (t-TCA) and andrographolide (AP), administering to a subject.
[0013] The Indian Application No. IN-KOL-2006-00056A titled “A process of preparing Herbosomes with Andrographolide, having better hepatoprotective activity and product thereof” discloses Herbosomes with Andrographolide, a novel compound comprising lipophilic complexes of Andrographolide with phospholipids and the preparation of these complexes by non-conventional methods. Herbosomes are the concept of value addition to phytoconstituents to develop a specific dosage form with more therapeutic potency man using it as such, which increase the availability of the constituents for a longer time in blood and help in curing the diseases to a higher extent. Hence, the Herbosomes is a value-added herbal formulation with isolated phytonutrients having potential hepatoprotective activity. The novel compound produced prolonged significant hepatoprotective activity than the pure molecule at the same dose levels. Thus, resulting improvement in the pharmacokinetics and pharmacological parameters such that the compound can be used advantageously in the treatment of acute or chronic liver diseases.
[0014] Therefore, the existing plant-derived compounds for treating liver disease are accessible and do not require laborious pharmaceutical synthesis seems highly attractive. Furthermore, in spite of the advances in conventional medicine in the last decades, professionals and the lay public of developed countries pay increasing attention to phytomedicine. Although, there are several plant-based drugs comprising hundreds of medicinal plants that have been reported activities for liver support. However, it is practically impossible to understand the potential of each plant and also to consume several plant drugs.
[0015] Hence, there is a need for an improved synergistic polyherbal composition, comprising mixture of potential liver supporting formula effective against various liver disorders and besides possess hepatoprotective activity against various hepatotoxins.
Summary of the invention
[0016] The invention discloses a polyherbal composition for an effective management and treatment of various liver disorders. In particular, the invention provides a synergistically effective polyherbal composition possessing liver supporting formula, effective against various liver disorders such as hepatitis, non-alcoholic fatty liver disease, jaundice, alcoholic liver disease etc., and besides hepatoprotective activity against various hepatotoxins such as alcohol, drugs, viruses and chemicals. The present invention also provides a method of preparing the synergistically effective polyherbal composition effective against various liver disorders.
[0017] The present invention, provides a polyherbal composition for liver support, comprising active constituents of plant extracts, wherein the plant extracts include root extract of Boerhaavia diffusa, an entire plant of Phyllanthus niruri, stem extract of Tinospora cordifolia, root extract of Berberis aristata, an entire plant of Andrographis paniculata, root extract of Capparis spinosa, root extract of Cyperus rotundus, fruit of Piper longum, root extract of Picrorhiza kurroa and pharmaceutically acceptable excipients thereof at defined concentrations. The defined concentration of plant extract comprises Boerhaavia diffusa 14.32%; Phyllanthus niruri 13.02%; Tinospora cordifolia 9.11%; Berberis aristate 6.51%; Andrographis paniculate 6.51%; Capparis spinosa 6.51%; Cyperus rotundus 6.51%; Piper longum 0.65% and Picrorhiza kurroa 6.51%.
[0018] Furthermore, the polyherbal composition also comprises pharmaceutically acceptable excipients is selected from the group consisting of microcrystalline cellulose (MCC), crospovidone, syloid 244, sodium starch glycolate, magnesium stearate, hydroxyl propyl methyl cellulose, PEG 6000, titanium dioxide, methylene chloride, iron oxide red, iron oxide black. The microcrystalline cellulose (MCC) is used as a diluent, Crospovidone and sodium starch glycolate is used as super-disintegrant, Syloid 244 is used as humectant and magnesium stearate is used as lubricant. Furthermore, the concentrations of pharmaceutically acceptable excipients such as microcrystalline cellulose (MCC) is 1.95%, crospovidone is 4.94%, syloid 244 is 0.97%, sodium starch glycolate is 4.55%, magnesium stearate is 0.97%, hydroxyl propyl methyl cellulose is 1.82%, PEG 6000 is 0.2%, titanium dioxide is 0.032%, iron oxide red is 0.175% and iron oxide black is 0.07%.
[0019] The polyherbal composition according to embodiment of the present invention is formulated as a tablet, capsule, injectable solutions, syrups, tinctures, transdermal patches, nanofibers, dry powder inhalers, metered dose inhalers and thereof.
[0020] Furthermore, the polyherbal composition is effective in normalizing elevated liver enzymes, increasing bile secretion, stimulating liver cell regeneration, improving liver functions, immunomodulation, detoxification and excretion capabilities of liver. Moreover, the composition also provides hepatoprotective activity against various hepatotoxins such as alcohol, drugs, viruses and chemicals. In yet another embodiment of the present invention, the polyherbal composition is effective in lowering elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and serum total bilirubin in liver disorder patients with abnormal liver function test (LFT).
[0021] Besides, the synergistically effective polyherbal composition is effective against hepatitis, non-alcoholic fatty liver disease, jaundice, alcoholic fatty liver disease, alcoholic hepatitis, drug induced hepatitis, viral hepatitis (other than B and C) and the like. Moreover, the concentration of active constituents used in the polyherbal composition is several fold lesser and of equivalent strength when compared to the prevailing compositions.

[0022] From the foregoing discussion, it is apparent that the polyherbal composition is an all-in-one formula with multiple active constituents responsible for liver support. Although there exist hundreds of medicinal plants for liver support. However, it is practically impossible to understand the potential of each plant and to consume several plant drugs. Hence the polyherbal composition containing mixture of potential liver supporting activity would be a boon. In addition, from the above clinical study of polyherbal composition it is apparent that the plant extracts of the polyherbal composition such as Phyllanthus niruri, Boerhaavia diffusa, Cyperus rotundus and Andrographis panniculata reduce visceral adiposity, improve liver enzymes abnormalities, decrease hepatic lipid peroxidation, inhibit liver X receptor mediated activation of sterol regulatory element binding protein-1c and fat accumulation in liver cells in fatty liver disease. Furthermore, the plant extracts Piper longum, Boerhaavia diffusa, Picrorhiza kurroa, Tinospora cordifolia, and Andrographis paniculata are useful in treating alcoholic hepatitis. These ingredients provide hepato-protection by preventing the leakage of biochemical marker enzymes from the cells into the blood. Phyllanthus niruri, Berberis aristata, Andrographis panniculata, Cyperus rotundus, and Boerhaavia diffusa also helps to inhibit viral entry, inhibit cellular DNA polymerase activity, provide anti-oxidant support, bring down elevated liver enzymes and provide overall protection to liver in viral hepatitis. Andrographis panniculata, Cyperus rotundus, Piper longum, Boerhaavia diffusa and Capparis spinosa are useful in normalizing reactive oxygen species levels, inhibiting cellular proliferation, and inducing apoptosis in HepG2 cell, normalize elevated liver enzymes in drug induced hepatotoxicity.
[0023] Therefore, almost all the ingredients of the polyherbal composition possess hepatoprotective activity against various hepatotoxins such as alcohol, drugs, viruses and chemicals. The plant extracts help to normalize elevated liver enzymes, increases bile secretion from liver and improves overall liver function. Hence, by the virtue of synergistic activity of the ingredients, the polyherbal composition is effective in liver disorder patients with abnormal liver function tests.
Brief description of drawings
[0024] FIG. 1 tabulates the range of concentrations of plant extracts used in polyherbal composition, according to an embodiment of the present invention.
[0025] FIG. 2 tabulates the concentrations of plant extracts used in polyherbal composition, according to an embodiment of the present invention.
[0026] FIG. 3 illustrates a table providing an insight on polyherbal composition versus prevailing compositions, according to an embodiment of the present invention.
[0027] FIG 4 illustrates a flowchart to explain the method of preparation of polyherbal composition, according to an embodiment of the present invention.
[0028] FIG. 5 illustrates a graph of change in Aspartate aminotransferase (AST) versus duration in subjects treated with the polyherbal composition, according to an embodiment of the present invention.
[0029] FIG. 6 illustrates a graph of change in Alanine aminotransferase (ALT) versus duration in subjects treated with the polyherbal composition, according to an embodiment of the present invention.
[0030] FIG. 7 illustrates a graph of change in serum total bilirubin versus duration in subjects treated with the polyherbal composition, according to an embodiment of the present invention.
[0031] FIG. 8 illustrates a graph of change in serum direct bilirubin versus duration in subjects treated with the polyherbal composition, according to an embodiment of the present invention.
[0032] FIG. 9 illustrates a graph of change in serum indirect bilirubin versus duration in subjects treated with the polyherbal composition, according to an embodiment of the present invention.
[0033] FIG. 10 illustrates a graph of change in serum alkaline phosphatase versus duration in subjects treated with the polyherbal composition, according to an embodiment of the present invention.
[0034] FIG. 11 illustrates a graph of change in Gamma-Glutamyl Transpeptidase (GGTP) versus duration in subjects treated with the polyherbal composition, according to an embodiment of the present invention.
[0035] FIG. 12 illustrates a graph of change in mean total protein versus duration in subjects treated with the polyherbal composition, according to an embodiment of the present invention.
[0036] FIG. 13 illustrates a graph of change in serum albumin versus duration in subjects treated with the polyherbal composition, according to an embodiment of the present invention.
[0037] FIG. 14 illustrates a graph of change in mean serum albumin/ globulin ratio versus duration in subjects treated with the polyherbal composition, according to an embodiment of the present invention.
[0038] FIG. 15 illustrates a table providing retention time for each plant extract in polyherbal composition, according to an embodiment of the present invention.
[0039] FIG. 16 illustrates a HPLC chromatogram of plant extracts of polyherbal composition, according to an embodiment of the present invention.
Detailed description of the invention
[0001] In order to more clearly and concisely describe and point out the subject matter of the claimed invention, the following definitions are provided for specific terms, which are used in the following written description.
[0040] The terms “Subject” and “Patient” are used interchangeably herein in reference, for example, to a mammalian subject, such as human subject, in one embodiment, a human.
[0041] The present invention relates to a polyherbal composition for an effective management and treatment of various liver disorders. The present invention more particularly relates to a synergistically effective polyherbal composition possessing liver supporting formula, effective against various liver disorders and besides provide hepatoprotective activity against various hepatotoxins such as alcohol, drugs, viruses and chemicals. The present invention also relates to method of preparing the synergistically effective polyherbal composition effective against various liver disorders.
[0042] According to one embodiment of the present invention, provides a polyherbal composition for liver support, comprising active constituents of plant extracts, wherein the plant extracts include root extract of Boerhaavia diffusa, an entire plant of Phyllanthus niruri, stem extract of Tinospora cordifolia, root extract of Berberis aristata, an entire plant of Andrographis paniculata, root extract of Capparis spinosa, root extract of Cyperus rotundus, fruit of Piper longum, root extract of Picrorhiza kurroa and pharmaceutically acceptable excipients thereof at defined concentrations.
[0043] According to one embodiment of the present invention, the active constituents of root extract of Picrorhiza kurroa includes Picroside l and ll, an entire plant of Andrographis paniculata includes Andrographolide, root extract of Berberis aristata includes Berberine and root extract of Boerhaavia diffusa includes Boeravinone-B. Besides, the concentration of Picroside l and ll is 5%, Andrographolide is 0.5%, Berberine is 0.5% and Boeravinone-B is 0.1%. The range of defined concentrations of plant extracts are provided in the FIG. 1 and the exact concentrations of plant extract is tabulated in a table in FIG. 2.
[0044] Furthermore, the polyherbal composition is a unique combination of nine standard plant extracts for effective management of various liver disorders. The ingredients possess hepatoprotective activity against various hepatotoxins such as alcohol, drugs, viruses and chemicals. The plant extracts of the polyherbal composition help to normalize elevated liver enzymes, increases bile secretion from liver and improves overall liver function. By virtue of synergistic activity of the ingredients present in the polyherbal composition, which is useful against hepatitis, non-alcoholic fatty liver disease, alcoholic fatty liver disease, jaundice, alcoholic hepatitis, drug induced hepatitis, viral hepatitis (other than B and C) and thereof.
[0045] Moreover, the plant extract Boerhaavia diffusa is a well-known medicinal plant and possesses immunomodulatory, hepato-protective, anti-fibrinolysis, anticancer, anti-diabetic, anti-inflammatory and diuresis activities. Boerhaavia diffusa also exhibited hepatoprotective activity against experimentally induced carbon tetrachloride hepatotoxicity in rats and mice. The extract also produced an increase in normal bile flow in rats suggesting a strong choleretic activity. Boerhaavia diffusa also has the potential to be used in liver cirrhosis. In combination with other plant extracts, Boerhavia diffusa possesses hepatoprotective activity against non-alcoholic fatty liver disease. Phyllanthus niruri is used to treat bronchitis, skin diseases, anemia, asthma, anorexia and indigestion. Phyllanthus niruri has been reported to exhibit marked anti-hepatitis B virus surface antigen activity in in-vivo and in-vitro studies. Furthermore, Phyllanthus niruri possesses lipid lowering, anti-spasmodic, analgesic activities and also, helps to repair fatty liver and liver damage. Phyllanthus niruri possesses hepato-protective activity against various toxins such as drug and alcohol. Tinospora cordifolia commonly known, as “Amrita” or “Guduchi” is an important drug of Indian Systems of Medicine (ISM) and used in medicines since times immemorial. The drug is well known Indian bitter and prescribed in fevers, diabetes, dyspepsia, jaundice, urinary problems, skin diseases, chronic diarrhea and dysentery. Moderate alcohol intake is hepatotoxic and decreases intestinal absorption. Tinospora cordifolia treatment effectively increased the intestinal absorption and retaining power of liver that regulated alcohol-induced multivitamin deficiency. Furthermore, Tinospora cordifolia also possesses hepato-protective and immunomodulatory activities.
[0046] Yet another ingredient of the polyherbal composition includes Berberis aristata, wherein Berberis aristata is used as a bitter tonic, stomachic, cholagogue, antiperiodic and alterative, in cases of remittent as well as intermittent fevers and also in debility consequent there from and is very effective in periodic neuralgia and menorrhagia. Berberis aristata also possesses hepatoprotective and immunomodulatory activities. In vivo data from various animal models confirm Berberis aristata’s beneficial role in preventing or treating non-alcoholic fatty liver disease. Berberis aristata has been shown to reduce liver necrosis both in non-alcoholic steatosis and in steatosis due to hepatitis C infection. Yet another ingredient of the polyherbal composition, Andrographis paniculata has been reported to have antibacterial, antifungal, antiviral, choleretic, hypoglycemic, hypocholesterolemic, and adaptogenic effects. Besides, Andrographis paniculata helps to protect the liver against ethanol induced liver toxicity by possibly reducing the rate of lipid peroxidation and increasing the antioxidant defense mechanism in rats. Andrographis paniculata also possesses hepato-protective activity against drug induced hepatotoxicity.
[0047] Capparis spinosa yet another ingredient of the polyherbal composition has been used traditionally to prevent or treat a number of health disorders such as diabetes, hepatitis, obesity, and kidney problems. Capparis spinosa also possesses, anti-oxidant, anti-microbial, anti-inflammatory, hepatoprotective, anti-pyretic, diuretic properties. Furthermore, Picrorhiza kurroa yet another ingredient of the polyherbal composition is a well-known herb in the Ayurvedic system of medicine and has traditionally been used to treat disorders of the liver and upper respiratory tract, reduce fever, and to treat dyspepsia, chronic diarrhea, and scorpion sting. Picrorhiza kurroa has been shown to stimulate liver regeneration in rats, possibly via stimulation of nucleic acid and protein synthesis. Besides, Picrorhiza kurroa is useful in treating non-alcoholic fatty liver disease and also effective against alcohol induced hepatotoxicity.
[0048] Cyperus rotundus yet another ingredient of the polyherbal composition is a rhizome and considered to be an astringent, diuretic, analgesic, antispasmodic, carminative, antitussive, litholytic, sedative, and antibacterial. Cyperus rotundus possesses hepato-protective activity against various toxins and also prevents non-alcoholic fatty liver disease through the inhibition of liver X Receptor a-Mediated activation of sterol regulatory element binding protein-1c. Yet another ingredient of the polyherbal composition includes Piper longum also known as pippali has been used for various respiratory and digestive disorders. Piper longum is also used to treat various liver disorders and protects liver from damages due to various reasons. Furthermore, Piper longum also helps to increase bioavailability of the other herbs present in the formulation.
[0049] According to one embodiment of the present invention, the pharmaceutically acceptable excipients are selected from the group consisting of microcrystalline cellulose (MCC), crospovidone, syloid 244, sodium starch glycolate, magnesium stearate, hydroxyl propyl methyl cellulose, PEG 6000, titanium dioxide, methylene chloride, iron oxide red and iron oxide black. The microcrystalline cellulose (MCC) is used as a diluent, crospovidone and sodium starch glycolate is used as super-disintegrant, syloid 244 is used as humectant and magnesium stearate is used as lubricant. Furthermore, the concentrations of pharmaceutically acceptable excipients such as microcrystalline cellulose (MCC) is 1.95%, crospovidone is 4.94%, syloid 244 is 0.97%, sodium starch glycolate is 4.55%, magnesium stearate is 0.97%, hydroxyl propyl methyl cellulose is 1.82%, PEG 6000 is 0.2%, titanium dioxide is 0.032%, iron oxide red is 0.175% and iron oxide black is 0.07%.
[0050] According to one embodiment of the present invention, the polyherbal composition is formulated as a tablet, capsule, injectable solutions, syrups, tinctures, transdermal patches, nanofibers, dry powder inhalers, metered dose inhalers and thereof.
[0051] According to one embodiment of the present invention, the polyherbal composition is effective in normalizing elevated liver enzymes, increasing bile secretion, stimulating liver cell regeneration, improving liver functions, immunomodulation, detoxification and excretion capabilities of liver. Moreover, the composition also provides hepatoprotective activity against various hepatotoxins such as alcohol, drugs, viruses and chemicals. In yet another embodiment of the present invention the polyherbal composition is effective in lowering elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and serum total bilirubin in liver disorder patients with abnormal liver function test (LFT).
[0052] According to one embodiment of the present invention, the synergistically effective polyherbal composition is effective against hepatitis, non-alcoholic fatty liver disease, jaundice, alcoholic fatty liver disease, alcoholic hepatitis, drug induced hepatitis, viral hepatitis (other than B and C) and the like. Moreover, the concentration of active constituents used in the polyherbal composition is several fold lesser and of equivalent strength when compared to the prevailing compositions. The FIG.3 provides an insight on polyherbal composition versus prevailing compositions.
[0053] FIG. 4 illustrates a flowchart to explain the method for preparation of polyherbal composition for liver support, according to an embodiment of the present invention. FIG. 4 represents a flowchart describing the method for preparation of polyherbal composition for liver support, the method (100) comprising dispensing and sifting separately plant extracts including root extract of Boerhaavia diffusa, an entire plant of Phyllanthus niruri, stem extract of Tinospora cordifolia, root extract of Berberis aristata, an entire plant of Andrographis panniculata, root extract of Capparis spinosa, root extract of Picrorhiza kurroa, root extract of Cyperus rotundus and fruit of Piper longum through mesh size 20 of defined concentrations and collecting the said plant extracts in separate double line polybag (102). Further, sifting pharmaceutically acceptable excipients including microcrystalline cellulose, crospovidone, sodium starch glycolate, sylloid 244 through mesh size 40 and magnesium stearate through mesh size 60 and collecting the said pharmaceutically acceptable excipients in separate double line polybag (104). The method further involves mixing the sifted plant extracts and pharmaceutically acceptable excipients in a Rapid Mixer Granulator (RMG) with impeller at slow speed and chopper off for 10 minutes and then adding binder solution IPA to the obtained powder mixture in the RMG and mixing the said powdered mixture for 4 to 5 mins with impeller at slow speed with chopper off (106). Furthermore, the method involves kneading the said powdered mixture for further 5 to 6 minutes with impeller at fast speed and chopper running at slow speed till end point of granule formation is observed and thereby adding extra quantity of water if required (108). In addition, the method involves drying the granules in fluid bed dryer at a temperature of 400C to 450C till the granules achieve required Loss on Drying (LOD) and thereby determining the LOD content using IR moisture analyser at a limit of 3 to 4% w/w and at temperature 1050C (110).
[0054] Subsequently, the method (100) involves sifting the dried granules through mesh size 16 using vibratory sifter and passing the retained granules through 2.4 mm perforated stainless-steel screen on multi-mill with medium speed, knives forward and then passing the milled granules through mesh size 16 and collecting the milled granules with the sifted granules in a stainless-steel bin (112). Further, transferring the sifted granules to a blender along with pharmaceutically acceptable excipients including crospovidone, sodium starch glycolate, microcrystalline cellulose (MCC), sylloid 244 for 10 minutes and adding magnesium stearate previously passed through mesh size 60 and mixing for 3 minutes (114). Besides, the method involves unloading the obtained lubricated blend and collecting the lubricated blend in a double-line polybag (116). Further compressing the lubricated blend by using compression machine to form tablets (118). Then dispensing polyethylene glycol, HPMC 6 CPS, titanium dioxide, purified talc, isopropyl alcohol, iron oxide red, iron oxide black and methylene chloride to make a coating solution to coat the obtained tablets (120). Eventually, packing the tablets so obtained in a HDPE bottle with proper quality of sealing and labelling (122).
[0055] Furthermore, in order to evaluate the efficacy and safety of the polyherbal composition for liver support in liver disorder patients with abnormal Liver Function Test (LFT) an open-labeled, multicenter, non-comparative, interventional and prospective clinical study was conducted. Additionally, the chemical characteristics of the polyherbal composition is also evaluated in terms of High-Performance Liquid Chromatography (HPLC).
[0056] The present invention may be more clearly understood with reference to the following examples of the invention which are given by way of example only. One has to consider that the following examples are included to demonstrate certain non-limiting aspects of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the invention. However, those of skilled in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.
Example 1: Safety and Efficacy of polyherbal composition for liver support in patients suffering from liver disorders
[0057] The primary objective of the study was to evaluate the efficacy of polyherbal composition for liver support in patients suffering from liver disorders by assessing SGOT or AST (Aspartate Aminotransferase) and SGPT or ALT (Alanine aminotransferase). Moreover, the study was further evaluated to study the efficacy of polyherbal composition for liver support in patients suffering from liver disorders by assessing serum total bilirubin and also by assessing adverse events, vital parameters and safety laboratory parameters.
[0058] The subjects involved in study for determining the efficacy of polyherbal composition for liver support includes males or females 18-65 years of age (both inclusive). Subjects with hepatic disorder with abnormal LFT with or without signs and symptoms were also included. Therefore, 56 subjects were involved in the clinical study.
[0059] During the course of treatment, the subjects were advised to consume 2 tablets of polyherbal composition of the present invention twice daily orally after meals with water for 2 months or till complete normalization (all the parameters of LFT tests should be within normal limits) of liver functions whichever was earlier. Subjects were advised to stop consuming alcohol and drugs that cause harm to liver. Furthermore, subjects were advised lifestyle modification (nutritious diet, exercise etc.) Subjects were called for follow up on day 15, day 30, day 45 and day 60 or till complete normalization of liver functions whichever was earlier.
[0060] Furthermore, the efficacy of the polyherbal composition was assessed by improvement in the hepatic condition as measured through biochemical and clinical improvement. Biochemical improvement was assessed through ALT, AST, Alkaline phosphatase, serum total, direct and indirect bilirubin levels whereas, clinical improvement was assessed through abdominal pain, abdominal tenderness, jaundice, fatigue, loss of appetite, nausea, vomiting and itching. Subjects were also monitored for the clinical symptoms of liver dysfunctions like chills, headache, malaise, anorexia, nausea, vomiting, diarrhea, upper abdominal pain, tender liver, enlarged spleen, dark urine, and yellow tint to sclera. Furthermore, subjective clinical improvement assessment was done during the treatment on screening visit, day 0, day 15, day 30, day 45 and day 60. The improvement in the liver function tests (ALT, AST, Alkaline phosphatase, serum total, direct and indirect bilirubin levels) was assessed at screening visit, Day 15, Day 30, Day 45 and Day 60. If subject’s LFTs (ALT, AST, Alkaline phosphatase, serum total, direct and indirect bilirubin levels) became normal any time during the study period and before day 60, that subject was treated as completer and all his safety lab investigations and ECG was done.
[0061] FIG.5 illustrates the graph on change in Aspartate aminotransferase (AST) versus duration in subjects treated with the polyherbal composition. Change in Aspartate aminotransferase (AST) or SGOT level was studied by utilizing the mean AST level at the beginning of the study. The mean AST level at the beginning of the study was 86.37 ± 69.68, that reduced significantly to 65.61 ± 44.87 (24.03%), 49.00 ± 39.70 (43.26%), 39.73 ± 37.25 (54%) and 37.67 ± 35.47 (56.38%) on day 15, day 30 day 45 and day 60 respectively in subject treated with composition of the present invention.
[0062] FIG. 6 illustrates the graph on change in Alanine aminotransferase (ALT)versus duration in subjects treated with the polyherbal composition. Change in Alanine aminotransferase (ALT) or SGPT was also studied. At baseline visit, the mean ALT level was 66.68 ± 36.91 that reduced significantly to 53.98 ± 27.97 (19.05%), 40.77 ± 21.56 (38.86%), 33.52 ± 17.27 (49.73%) and 31.87 ± 12.40 (52.20%) on day 15, day 30, day 45 and day 60 respectively in subject treated with the composition of the present invention.
[0063] FIG. 7 illustrates the graph on change in serum total bilirubin versus duration in subjects treated with the polyherbal composition. The change in serum total bilirubin was also studied. The mean serum total bilirubin at the beginning of the study was 02.10 ± 00.86, which reduced significantly to 01.55 ± 00.73 (26.19%), 01.15 ± 00.46 (45.24%), 00.97 ± 00.21 (53.81%) and 00.95 ± 00.18 (54.76%) on day 15, day 30, day 45 and day 60 respectively in subject treated with the composition of the present invention.
[0064] FIG. 8 illustrates the graph on change in serum direct bilirubin versus duration in subjects treated with the polyherbal composition. Change in serum direct bilirubin was also analyzed, wherein at the baseline visit, the mean serum direct bilirubin was 00.77 ± 00.45, which reduced significantly to 00.54 ± 00.40 (29.87%), 00.37 ± 00.24 (51.95%), 00.27 ± 00.13 (64.94%) and 00.26 ± 00.12 (66.23%) on day 15, day 30, day 45 and day 60 respectively in subject treated with the composition of the present invention.
[0065] FIG. 9 illustrates the graph on change in serum indirect bilirubin versus duration in subjects treated with the polyherbal composition. The change in serum indirect bilirubin was studied with respect to the polyherbal composition, wherein the mean serum indirect bilirubin at baseline visit was 01.35 ± 00.55, which reduced significantly to 01.01 ± 00.46 (25.19%), 00.78 ± 00.31 (42.22%), 00.70 ± 00.20 (48.15%) and 00.70 ± 00.20 (48.15%) on day 15, day 30, day 45 and day 60 respectively in subject treated with the composition of the present invention.
[0066] FIG. 10 illustrates the graph on change in serum alkaline phosphatase versus duration in subjects treated with the polyherbal composition. The change in serum alkaline phosphatase was analyzed, in which at the baseline visit, the mean serum alkaline phosphatase was 122.61 ± 41.49, which did not change on day 15 and day 30. The mean serum alkaline phosphatase reduced insignificantly from baseline visit to 118.06 ± 33.01 and 118.63 ± 32.09 on day 45 and day 60 respectively in subject treated with the composition of the present invention.
[0067] FIG. 11 illustrates the graph on change in Gamma-Glutamyl Transpeptidase (GGTP) versus duration in subjects treated with the polyherbal composition. The change in Gamma-Glutamyl Transpeptidase (GGTP) was studied, wherein at the baseline visit, the GGTP level was 80.47 ± 120.53 significantly reduced to 64.32 ± 085.53 on day 30. The mean GGTP level reduced significantly from baseline visit to 57.90 ± 066.08 and 53.93 ± 055.15 on day 45 and day 60 respectively in subject treated with the composition of the present invention.
[0068] FIG. 12 illustrates the graph on change in mean total protein versus duration in subjects treated with the polyherbal composition. The change in mean total protein was studied with respect to the polyherbal composition, wherein the mean total protein at baseline visit was 07.38 ± 00.61 that did not change till day 30. The mean total protein insignificantly reduced from baseline visit to 07.20 ± 00.72 and 07.25 ± 00.56 on day 45 and day 60 respectively in subject treated with the composition of the present invention.
[0069] FIG. 13 illustrates the graph on change in serum albumin versus duration in subjects treated with the polyherbal composition. The change in serum albumin was studied, wherein at baseline visit, the mean serum albumin was 04.20 ± 00.49, which remained same till day 30. Further, the mean serum albumin reduced insignificantly from baseline visit to 04.14 ± 00.43 and 04.15 ± 00.42 on day 45 and day 60 respectively in subject treated with the composition of the present invention.
[0070] FIG. 14 illustrates the graph on change in mean serum albumin/ globulin ratio versus duration in subjects treated with the polyherbal composition. The change in mean serum albumin/globulin ration was studied, wherein at the baseline visit, the mean serum albumin/globulin ratio was 01.38 ± 00.43, which did not change till day 30. Further, the mean serum albumin/globulin ratio increased insignificantly to 01.39 ± 00.43 on day 45. Further, the mean serum albumin/globulin ratio did not change from its baseline value in subject treated with the composition of the present invention.
[0071] In addition, to the above-mentioned studies including biochemical and clinical improvement, the symptoms of subjects after successful completion of medications for two months are also assessed. The results interpreted that there was a significant improvement in symptoms such as abdominal pain, abdominal tenderness, nausea, vomiting, fatigue, jaundice, anorexia and pruritus in response to the composition of the present invention.
[0072] Hence, the safety and efficacy of polyherbal composition in liver disorder subjects with abnormal liver function tests is evaluated and it is evident that the polyherbal composition was significantly effective in normalizing liver functions from day 15 onwards. Furthermore, at the end of the treatment with the polyherbal composition, liver functions were within normal limits in all the subjects. The polyherbal composition was equally effective in all types of liver disorders as evidenced by significant improvement observed in liver function tests. Moreover, the polyherbal composition was significantly effective in improving symptoms of liver disorders such as abdominal pain, abdominal tenderness, nausea, vomiting and fatigue from day 15 onwards till day 60. A significant improvement in symptoms such as anorexia, pruritus, jaundice and bowel movement was also observed.
[0073] Therefore, to conclude the polyherbal composition is safe in liver disorder patients with abnormal liver function tests. Polyherbal composition is significantly effective in normalizing elevated liver enzymes in liver disorder patients with abnormal liver function test. The effect of the polyherbal composition in terms of normalization of elevated liver enzymes can be seen after 15 days of treatment. The polyherbal composition is also significantly effective in improving symptoms of liver disorders such as abdominal pain, abdominal tenderness, nausea, vomiting, fatigue, jaundice, anorexia and pruritus. The polyherbal composition is also effective in reducing inflammation of liver (hepatitis) and normalizing fatty liver disease as observed in USG findings. Thus, the polyherbal composition is safe and effective in subjects suffering from non-alcoholic fatty liver disease, alcoholic fatty liver disease, alcoholic hepatitis, drug induced hepatitis and viral hepatitis (other than B and C).
Example 2: Study on chemical characteristics of the polyherbal composition evaluated in terms of High-Performance Liquid Chromatography (HPLC)
[0074] The chromatogram is developed under the following chromatographic conditions.
Chromatographic conditions include preparation of buffer solution, wherein the buffer solution includes Mobile phase A and Mobile phase B includes Acetonitrile. The column used in the HPLC chromatography used in the study is Hypersil BDS, 3V, 250 x 4.6 mm and 5µm, column temperature 35°C, sample temperature 15°C, wavelength for different active constituents of plant extracts such as for Picroside-II, Andrographolide, Berberine, Phyllanthin is 220nm and for Picroside-I is 280nm. Furthermore, the flow rate is 1.0 mL/min, injection volume is 20 ?L, run time is 50 minutes, elution is gradient and diluent used is methanol.
[0075] Preparation of individual standard stocks
[0076] Individual standard stock solution is prepared for plant exacts as discussed below.
[0077] Picorside-I Standard stock: (100 µg/ mL) is prepared by transferring accurately weighed quantity of 2.5 mg of Picroside-I reference standard (Natural remedies) to a 25 mL volumetric flask. Adding about 15 mL of methanol and sonicate to dissolve. Make volume up to the mark with methanol and mix well.
[0078] Picorside-II Standard stock: (100 µg/ mL) is prepared by transferring accurately weighed quantity of 2.5 mg of Picroside-II reference standard (Natural Remedies) in to a 25 mL volumetric flask. Adding about 15 mL of methanol and sonicate to dissolve. Make volume up to the mark with Methanol and mix well.
[0079] Androgrpholide Standard stock: (100 µg/ mL) is prepared by transferring accurately weighed quantity of 2.5 mg of Andrographolide reference standard (Natural Remedies) in to a 25 mL volumetric flask. Adding about 15 mL of methanol and sonicate to dissolve. Make volume up to the mark with Methanol and mix well.
[0080] Berberine Standard stock: (100 µg/ mL) is prepared by transferring accurately weighed quantity of 2.5 mg of Berberine reference standard (TCI) in to a 25 mL volumetric flask. Adding about 15 mL of methanol and sonicate to dissolve. Make volume up to the mark with Methanol and mix well.
[0081] Boeravinone-B Standard stock: (100 µg/ mL) is prepared by transferring accurately weighed quantity of 2.5 mg of Boeravinone-B reference standard (Natural Remedies) in to a 25 mL volumetric flask. Adding about 15 mL of methanol and sonicate to dissolve. Make volume up to the mark with Methanol and mix well.
[0082] Phyllanthin Standard stock: (100 µg/ mL) is prepared by transferring accurately weighed quantity of 2.5 mg of Phyllanthin reference standard (Natural Remedies) in to a 25 mL volumetric flask. Adding about 15 mL of methanol and sonicate to dissolve. Make volume up to the mark with Methanol and mix well.
[0083] Further, Standard mix preparation (10 µg/ mL) is prepared by Pipetting 1 mL of each Picroside-I, Picroside-II, Andrographolide, Berberine, Phyllanthin and 0.5 mL of Boeravinone-B Standard stocks in to 10mL volumetric flask and diluting up to the mark with Methanol mix well and use.
[0084] In addition, sample preparation is made by selecting randomly not less than 20 capsules and calculating average weight of capsules and uniformly mix the blend of all capsules. Transfering an accurately weighed portion of the capsule blend about 100 mg in to a 50 mL volumetric flask. Adding about 40 mL of Methanol and sonicate for 30 minutes with intermediate shaking. Making up volume up to the mark with Methanol and mix well. Filtering the solution through 0.45 ? nylon filter; collecting the filtrate by discarding first 3 mL of the filtrate.
[0085] Moreover, the system suitability includes Chromatograph standard preparation and recording the peak response. % RSD of five replicate standard injections should not be more than 2.0%, the column efficiency should not be less than 2000 theoretical plates and tailing factor should not be more than 2.0 for all analyte peaks.
[0086] The chromatographic procedure includes separately inject diluent, standard preparation and sample preparation into the chromatograph. Then recording the chromatograms and measuring the response for the analyte peaks. Further the result of the HPLC chromatograms including Retention time for each sample has been tabulated in table format hereunder FIG. 15 and FIG. 16 illustrates the chromatograms.
[0087] Besides, the quantity of each sample in mg per tablets and percentage assay of each sample was calculated using below formula:
Sample
(mg/tablet) = At x Wt.std x 1 x 50 x P x Avg.Wt
As 25 10 Wt.spl 100

% Assay = (mg/tablet found) x 100
L.C.

where,
At : Average area of analyte peak in Sample Solution
As : Average area of analyte peak in Standard Solution
Wt. std. : Weight of standard in mg
Wt. spl. : Weight of sample in mg
Avg.Wt : Average weight in mg
P : Potency of Standard in % (as such basis)
L.C. : Label Claim in mg
[0088] From the foregoing discussion, it is apparent that the polyherbal composition is an all-in-one formula with multiple active constituents responsible for liver support. Although there exist hundreds of medicinal plants for liver support. However, it is practically impossible to understand the potential of each plant and to consume several plant drugs. Hence, the polyherbal composition containing mixture of potential liver supporting activity would be a boon. In addition, the plant extracts of the polyherbal composition such as Phyllanthus niruri, Boerhaavia diffusa, Cyperus rotundus and Andrographis panniculata reduce visceral adiposity, improve liver enzymes abnormalities, decrease hepatic lipid peroxidation, inhibit liver X receptor mediated activation of sterol regulatory element binding protein-1c and fat accumulation in liver cells in fatty liver disease. Furthermore, the plant extracts Piper longum, Boerhaavia diffusa, Picrorhiza kurroa, Tinospora cordifolia, and Andrographis paniculata are useful in alcoholic hepatitis. These ingredients provide hepato-protection by preventing the leakage of biochemical marker enzymes from the cells into the blood. Phyllanthus niruri, Berberis aristata, Andrographis panniculata, Cyperus rotundus, and Boerhaavia diffusa also helps to inhibit viral entry, inhibit cellular DNA polymerase activity, provide anti-oxidant support, bring down elevated liver enzymes and provide overall protection to liver in viral hepatitis. Andrographis panniculata, Cyperus rotundus, Piper longum, Boerhaavia diffusa and Capparis spinosa are useful in normalizing reactive oxygen species levels, inhibiting cellular proliferation, and inducing apoptosis in HepG2 cell, normalize elevated liver enzymes in drug induced hepatotoxicity.
[0089] Therefore, almost all the ingredients of the polyherbal composition possess hepatoprotective activity against various hepatotoxins such as alcohol, drugs, viruses and chemicals. The plant extracts also help to normalize elevated liver enzymes, increases bile secretion from liver and improves overall liver function. Hence, by the virtue of synergistic activity of the ingredients, the polyherbal composition is effective in liver disorder patients with abnormal liver function tests.