Title of Invention

''A SYNERGISTIC POLYPHAARMACEUTICAL COMPOSITION FOR TREATMENT OF VIRAL HEPATITIS AND JAUNDICE''

Abstract

A synergistic polypharmaceutical composition for treatment of viral hepatitis and jaundice comprising of two parts, the first part and the second part being present in the ratio of 3-7 : 93-97 wherein the first part comprises of dried extracts of Cichorium intybus, Tamarix dioca, Rubia cordifolia, Rheum emodi, Cassia occidentalis, Vitex negunda, Carea arborea, Plantago major, Rosa damascena, Solanum xanthocarpum, Solanum nigrum, Pimpinella anisum, Cuscuta reflexa, and Cyperus scariosus, and the second part comprises of Ammonium chloride, Cucurma longa, Piper nigrum.

Full Text

FIELD OF INVENTION This invention relates to synergistic polypharmaceutical composition known as Jigrol for the treatment of viral hepatitis and jaundice. BACKGROUND Acute viral hepatitis is one of the major health problem in India and other developing countries. The spread of the disease is due to water contamination and blood borne infections, poor sanitary conditions and unhygienic environment. At present, there is no specific drug available for the cure and management for viral hepatitis caused by hepatitis -B virus which can ameliorate symptom & enhance recovery. Steroids have been used for the treatment of this disease, but it was found that steroids are not effective because the disease often relapses. Thang-kuu-tin" a drug known in Taiwan was used for the treatment of toxic liver injury, but the same was not effective in hepatitis - B (HBV) in animal models. Phylanthus amara was found 59% effective in clearing HbsAg (virus) carrier state. In these cases, HBsAg was a marker of clearance and not HBV-DNA Polymerase (Enzymes) so that specificity of drug action is not explicit. The object of this invention is to develop a poly-pharmaceutical composition known as Jigrol in tablet from consisting of herbs and chemicals, which could treat the viral hepatitis effectively without producing any toxic effects in the major parenchymatous organs of the body. ' To achieve the said objective, studies were carried out for the treatment of viral hepatitis and jaundice and it was found that certain herbs play a vital role in the management of liver disorder. This invention, therefore, provides the polypharmaceutical composition hereinafter referred to "Jigrol" which comprises: A synergistic polypharmaceutical composition for treatment of viral hepatitis and jaundice comprising of two parts, the first part and the second part being present in the ratio of 3-7 : 93-97 wherein the first part comprises of dried extracts of 6-10 percent Cichorium intybus seed, 14-18 percent Tamarix dioca leaf, 6-10 percent Rubia cordifolia stem, 14-18 percent Rheum emodi wood, 10-14 percent Cassia occidentalis leaf, 2-6 percent Vitex negunda leaf, 6-10 percent Carea Arborea leaf, 1-5 percent Plantago major stem, 8-12 percent Rosa damascena flower petal, 8-12 percent Solanum xanthocarpum whole plant, 6-10 percent Solanum nigrum whole plant, 6-10 percent Pimpinella anisum seed & fruit, 6-10 percent Cuscuta reflexa stem, and 2-6 percent Cyperus scariosus whole plant, and the second part comprises of 0.6-1.4 percent Ammonium chloride salt, 0.9-2.1 percent Cucurma longa tuber, 0.6-1.4 percent Piper nigrum and excepients & binders q.s. DETAIL DESCRIPTION OF THE INVENTION This invention, provides the synergistic polypharmaceutical composition hereinafter referred to "Jigrol" which comprises: Ingredients Quantity of herbs by percent Quantity of dry extract by parts A. DRY EXT. OF: Cichorium intybus (Seeds)- 6-10 Tamarix dioca (Leaves) 14-18 Rubia cordifolia (Stems) 6-10 Rheum emodi (wood) 14-18 Cassia occidentalis (Leaves) 10-14 Vitex negunda (Leaves) 2-6 Careya arborea (Leaves) 6-10 3-7 Plantago major (Stems) 1 -5 Rosa damascena (Flower Petals) 8-12 Solanum (Whole Plants) 8-12 Xanthocarpum Solanum nigrum (Whole Plants) 6-10 : Pimpinella anisum (seeds, fruits) 6-10 : Cuscuta reflexa (stems) 6-10 : Cyperus scariosus (Whole Plants) 2-6 : B. Ingredients Quantity by percent Ammonium Chloride (salt) 0.6-1.4 Curcuma longa (Tuber) 0.9-2.1 Piper Nigrum (Fruits) 0.6-1.4 Excepient & binders q.s The above mentioned herbal ingredients A are extracted in solvents and thereafter converted in the form of dry powder by heating. This dry powder 3-7 parts is then mixed with ingredients B in the proportion given in the above table. The said mixture is homogenized, granulated and compressed into tablets. This invention, further, includes process of preparing the unani composition known as Jigrol in tablet form, which comprises: - Preparing extracts with ethyl alcohol and distilled water of the following ingredients collectively: Ingredients Quantity of herbs by percent Quantity of dry extract by parts A. DRY EXT. OF: Cichorium intybus (Seeds)- 6-10 Tamarix dioca (Leaves) 14-18 Rubia cordifolia (Stems) 6-10 Rheum emodi (wood) 14-18 Cassia occidentalis (Leaves) 10-14 Vitex negunda (Leaves) 2-6 Careya arborea (Leaves) 6-10 3-7 Plantago major (Stems) 1 -5 Rosa damascene (Flower Petals) 8-12 Solanum (Whole Plants) 8-12 Xanthocarpum Solanum nigrum (Whole Plants) 6-10 : Pimpinella anisum (seeds, fruits) 6-10 : Cuscuta reflexa (stems) 6-10 : Cyperus scariosus (Whole Plants) 2-6 : - concentrating the said extract to powder form by heating, - mixing the said powder form 3-7 parts with the following ingredients B. Ingredient B Quantity by percent Ammoniun Chloride (salt) 0.6-1.4 Curcuma longa (Tuber) 0.9-2.1 Piper nigrum (Fruits) 0.6-1.4 Excepient & binders q.s homogenizing the aforesaid mixture to ensure uniformity and therapeutic value of the composition and thereafter compressing into tablets. The extracts of the ingredients A are prepared preferably in 60% ethyl alcohol to get the maximum yield and active constituents for the treatment of hepatitis -B virus disease. The doses recommended for the treatment of the disease, are 2 tablets 3 times a day or more as advised by the physician. The invention will now be described with respect to the following example. Example 1 Concentrated extracts of the following herbs are converted to powder from by heating. Ingredients Quantity of herbs by percent Quantity of dry extract by parts A. DRY EXT. OF: Cichorium intybus (Seeds)- 6-10 Tamarix dioca (Leaves) 14-18 Rubia cordifolia (Stems) 6-10 Rheum emodi (wood) 14-18 Cassia occidentalis (Leaves) 10-14 Vitex negunda (Leaves) 2-6 Careya arborea (Leaves) 6-10 3-7 Plantago major (Stems) 1-5 Rosa damascene (Flower Petals) 8-12 Solanum (Whole Plants) 8-12 Xanthocarpum Solanum nigrum (Whole Plants) 6-10 : Pimpinella anisum (seeds, fruits) 6-10 : Cuscuta reflexa (stems) 6-10 : Cyperus scariosus (Whole Plants) 2-6 : The extracts of the above mentioned ingredients are prepared in 60% ethyl alcohol or distilled water to get the maximum yield and active constituents and thereafter the said extracts are concentrated in powder form and mixed with the following ingredients B: Ingredient B Quantity by percent Ammoniun Chloride (salt) 0.6-1.4 Curcuma longa (Tuber) 0.9-2.1 Piper nigrum (Fruits) 0.6-1.4 Excepient & binders q.s The mixture is thereafter compressed into tablets of 250 mg or 500mg. Example 2 Concentrated extracts of the following herbs are converted to powder form by heating. Ingredients Quantity of herbs by percent Quantity of dry extract by parts A. DRY EXT. OF: Cichorium intybus (Seeds)- 8.00 Tamarix dioca (Leaves) 16.11 Rubia cordifolia (Stems) 8.00 Rheum emodi (wood) 16.11 Cassia occidentalis (Leaves) 12.11 Vitex negunda (Leaves) 4.00 Careya arborea (Leaves) 8.00 5.00 Plantago major (Stems) 3.33 Rosa damascene (Flower Petals) 10.00 Solanum (Whole Plants) 10.00 Xanthocarpum Solanum nigrum (Whole Plants) 8.00 : Pimpinella anisum (seeds, fruits) 8.00 Cuscuta reflexa (stems) 8.00 : Cyperus scariosus (Whole Plants) 4.00 : The extracts of the above mentioned ingredients are prepared in 60% ethyl alcohol or distilled water to get the maximum yield and active constituents and thereafter the said extracts are concentrated in powder form and mixed with the following ingredients B: Ingredients B Quantity by percent Ammoniun Chloride (salt) 0.6-1.4 Curcuma longa (Tuber) 0.9-2.1 Piper nigrum (Fruits) 0.6-1.4 Excepient & binders q.s The mixture is thereafter compressed into tablets of 250mg or 500 mg. CLINICAL TRIALS Patients of acute viral hepatitis but without surgical cause of jaundice were screened. Patients with confirmed viral hepatitis were given this drug after recording the baseline clinical and biochemical data. Patients of either sexes within the age group of 10-60 years and developing jaundice suggestive of acute viral hepatitis for the first time were included in the trial. Patients having complications like fulfillment, subfulfillment, hepatitis, acute Alcoholic hepatitis, drug induced hepatitis, chronic hepatitis and decompensated cirrhosis were excluded from the trial. Associated risk factors like IHD (Ichemic heart diseases) diabetes, metabolic encephalopathy, renal failure, CHF and hypertension were identified but nevertherless the drug was given to them as well after control of risk factor with the appropriate drug. For the convenience of data analysis with respect to the stage of illness patients wer arbitrarily divided in four groups. Group I: Patients with jaundice of less than eight days duration. Group II: Patients with history of jaundice of eight or more than eight days but less than fifteen days. Group III: Patients with jaundice with more than 15 days but less than 30 days. Group IV: Patients with history of jaundice with more than 30 days. This breakup was done with an intention to study the effect of Jigrol tablets as a first drug the initial stages of illness in the first group. The other 3 groups would show the effects of the drug in established cases of jaundice in later stages of illness. Patients underwent completely clinical and laboratory examinations one day before starting Jigrol tablets. The Lab. Investigations carried out include CBP.ESR, complete urine examination, blood urea, Random Blood Sugar, Serum creatinine, serum electrolytes, LFT Serum proteins with A/G Ratio, Prothrombin time and hepatitis markers. The drug was continued till the liver function tests reached normal level. The drug was administered in the form of tablets to be used in a dose of two tablets three times a day with water. (b) Immunological Study: HBs Ag testing was done by enzyme linked immunosorbant assay (ELISA) Auszyme II Abbott Laboratory, U.S.A. (c) Invitro Study: Water extract of Jigrol was added to known HBs Ag positive serum and incubated with Anti HBs, the control did not have water extract of Jigrol added to it. The reaction was read by ELISA Reader. (d) Invivo Study: One day old ducklings of Jekin duck (n=30) were infected with 50 micro litre of duck hepatitis B virus (DHBV) Positive serum containing 10x11 viral genome per micro litre. After 3 months of age those who showed viremia for 2 out of 4 weeks of followup were regarded as having stable viremia. They were then inoculated with: (a) The water extract of Jigrol (WEJ) : 200mg/kg body weight (n=10) (b) Normal Saline -.control group (n=10) The inoculation was done intraperitoneally daily for a period ranging from 10 to 12 weeks. DHBV-DNA determination was done from the sera of these duck every week by dot blot hybridization technique (Method of scott et al 1983) for 10 week of after last inoculation. (e) Toxicity Study: Autopsy was performed at the end of the follow up along with histology of liver, kidney, heart, lungs and pancreas to study toxic effect of the drug on the different organs. (f) Statistical Analysis The statistical analysis of biochemical data was done by calculation the mean, standard deviation (SD), standard error(SE), and mean standard error. The difference in values for a given parameter between week to week in each group were tested separately using the analysis of variance. The F ratio (significance of the result) and the level of significance was calculated using F (Max) test and Bartlet test. The variance for a given parameter in a specific week. In different groups were also tested. Appropriate log transformation of data was carried out to have an analysis, and paired T test to know the level of significance. RESULTS: The 500 patients presenting with acute viral hepatitis were admitted in to the trial. Of these 52 patients have irregular follow ups and therefore were not included in the statistical analysis. None of these 52 patients had any complications nor did they die. Of the 448 patients analysed 313 were male and 135 were female and their age range was 10-60 years. The results are summerised in Tables I to XVI given below and Figures 1 to 8 and bar diagrams with legends as shown in the accompanying drawings: TABLE-I AGE AND SEX DISTRIBUTION: (Table Removed) TABLE-2 SEROLOGY OF PATIENTS OF ACUTE VIRAL HEPATITIS TREATED WITH JIGROL (Table Removed) Sero conversion of HBsAg +ve patients in 1 year = 33/125. 26.4% TABLE-3 SYMPTOMATIC RECOVERY IN PATIENTS OF ACUTE VIRAL HEPATITIS TREATED WITH JIGROL (Table Removed) TABLE-4 OVERALL MEAN WEEKLY LEVELS OF S. BILITRUBIN, ALT, ALP IN PATIENTS TREATED WITH JIGROL (n=448) (Table Removed) ++ P TABLE-5 OVERALL MEAN WEEKLY FALL IN S.BILIRUBIN, ALT, ALP IN PATIENTS TREATED WITH JIGROL (Table Removed) TABLE-6 OVERALL MEAN WEEKLY PERCENTAGE FALL IN LEVELS OF S.BILIRUBIN, ALT, ALK. PHOS. (Table Removed) TABLE-7 MEAN WEEKLY LEVELS OF BILIRUBIN IN GROUP I - GROUP IV PATEIENTS WITH F RATIO AND LEVEL OF SIGNIFICANCE WITHIN EACH GROUP AND BETWEEN GROUPS. (Table Removed) F Ratio 1.04 1.16 0.70 0.50 1.44 0.01 ++ P TABLE-8 MEAN WEEKLY LEVEL OF ALT IN GROUP I To IV PATIENTS ALONG WITH F RATIO AND THE LEVEL OF SIGNIFICANCE. (Table Removed) F Ratio 0.50 2.31 2.70 1.50 2.58 5.48 ++P TABLE-9 MEAN WEEKLYLEVELS OF S.ALK.PHOS. IN GROUP I - IV PATIENTS ALONG WITH F RATIO AND LEVEL OF SIGNIFICANCE. (Table Removed) F Ratio 0.88 0.84 0.64 2.30 4.26 2.06 ++P + P * Not Significant TABLE-10 MEAN WEEKLY FALL IN S. BILIRUBIN IN GROUP I - GROUP IV PATIENTS (Table Removed) TABLE-11 MEAN WEEKLY FALL IN ALT LEVELS IN GROUP I - IV PATIENTS (Table Removed) TABLE-12 MEAN WEEKLY FALL IN ALK.PHOS. IN GROUP I - IV PATIENTS (Table Removed) TABLE-13 MEAN WEEKLY PERCENTAGE FALL IN S. BILIRUBIN IN GROUP I - IV PATIENTS (Table Removed) TABLE-14 MEAN WEEKLY PERCENTAGE FALL IN ALT LEVELS IN GROUP I - IV PATIENTS (Table Removed) TABLE-15 MEAN WEEKLY PERCENTAGE FALL IN ALK.PHOS. LEVELS IN GROUP I-IV PATIENTS (Table Removed) TABLE-16 Results of Invivo animal studies on the effect of extracts of Rheum Emodi and Jigrol for Duck hepatitis B virus carrier state (Table Removed) * per kg body wt LEGENDS Figure-1 showing time for recovery from clinical jaundice in patients treated with jigrol. Figure-2 showing time for recovery from fever in patients with acute viral hepatitis treated with jigrol. Figure-3 showing time for recovery from nausea and vomiting in patients with acute viral hepatitis with jigrol. Figure-4 showing time for recovery from abdominal pain and anorexia in patients of acute viral hepatitis treated with jigrol. Figure-5 showing mean weekly fall in Serum bilirubin levels in group I to IV patients of acute viral hepatitis treated with jigrol. Figure-6 showing mean weekly fall of ALT in group I to IV patients of acute viral hepatitis treated with jigrol. Figure-7 showing mean weekly fall of ALP in group I to IV patients of acute viral hepatitis treated with jigrol. Bar diagram showing frequency age distribution of patients (male & female) of active viral hepatitis treated with Jigrol. CLINICAL RECOVERY: All the 500 patients treated with Jigrol tablets recovered completely. The presenting symptoms apart from jaundice is descending order of incidence were urine colour, fever, loss of appetite, nausea, abdominal pain, vomiting, itching and change in colour of stool. Nausea was the first to recover followed by vomiting, fever, abdominal pain, itching, change in stool colour and urine colour in that order. More than 50% patients had complete clinical recovery by and end of two weeks of treatment and by the end of 3rd week 98% had clinical clearance of jaundice 100% recovery was seen by the 30th day. This was irrespective of the level of jaundice at the time of admission in to the trial. Fever was the next common symptoms which was cleared in 70% of cases, by sixth day and more than 95% cases were of apyrexial by 8th day. Nausea was present in 40% of cases and all recovered (100%) by the sixth day. The recovery from vomiting followed similar pattern and around 90% recovered before the 4th day. Loss of appetites (Anorexia) improved in more than 80% of cases within 8 days and by 2 weeks 90% cases had recovered. Itching was relieved in all (100%) by 14th day. Complete symptomatic recovery was observed in all patients within the study period. BIOCHEMICAL RECOVERY: The overall mean values of serum bilirubin, Alakaline phosphatase and ALT for all patients treated with herbal drug Jigrol were studied and analysed. It is very clear that there is a highly significant beneficial effects of the drug on the 3 biochemical parameters studied. (C) INVITRO STUDIES: Water extract of Jigrol tablets inhibited the reaction between HBs Ag and Anti HBS suggesting inhibition of HBV-DNA polymerase which is necessary for viral replication. (d) IN VIVO STUDIES: Group (a) Ducklings : 45% of animal had intermittent non-viraemic intervals. Group (b) Ducklings : One animal had complete clearance of BHBV. Where as 3 animals had intermittent non-viraemic intervals. Group (c) Ducklings: Intermittent effects of non-viraemia in 3 animals on therapy. Group (d) Ducklings : All animals had intermittend non-viraemia therapy. Group (e) Ducklings : Intermittent non-viraemia in on animal only. Group (f) Ducklings : Complete DHBV clearance of 3 animals (30%) intermittent non-viraemia in remaining 2 animals (28%). Group (g) Ducklings : (Control Group) Persistent viraemia present. (e) TOXICITY STUDY: All animals from group 'a1 to 'f'on autopsy did not show any abnormality. Histology of liver, kidney, spleen, lung and heart did not show any abnormality compared to control (g-group) animals. The composition of the present invention is a synergistic composition as opposed to being a mere admixture. I claim: 1. A synergistic polypharmaceutical composition for treatment of viral hepatitis and jaundice comprising of two parts, the first part and the second part being present in the ratio of 3-7: 93-97 wherein the first part comprises of dried extracts of 6-10 percent Cichorium intybus seed, 14-18 percent Tamarix dioca leaf, 6-10 percent Rubia cordifolia stem, 14-18 percent Rheum emodi wood, 10-14 percent Cassia occidentals leaf, 2-6 percent Vitex negunda leaf, 6-10 percent Carea Arborea leaf, 1-5 percent Plantago major stem, 8-12 percent Rosa damascena flower petal, 8-12 percent Solanum xanthocarpum whole plant, 6-10 percent Solanum nigrum whole plant, 6-10 percent Pimpinella anisum seed & fruit, 6-10 percent Cuscuta reflexa stem, and 2-6 percent Cyperus scariosus whole plant, and the second part comprises of 0.6-1.4 percent Ammonium chloride salt, 0.9-2.1 percent Cucurma longa tuber, 0.6-1.4 percent Piper nigrum and excepients & binders q.s. 2. A synergistic polypharmaceutical composition as claimed in claim 1 wherein said extracts are in a concentrated powder form. 3. A synergistic polypharmaceutica! composition as claimed in claim 1 wherein said first and second parts are mixed homogeneously and compressed into tablets. 4. A synergistic polypharmaceutical composition as claimed in claim 1 wherein the ratio of the first and the second part is 5:95. 5. A synergistic polypharmaceutical composition as claimed in claim 4 wherein the composition of the first part comprises dried extracts of 8 percent Cichorium intybus seed, 16.11 percent Tamarix dioca leaf, 8 percent Rubia cordifolia stem, 16.11 percent Rheum emodi wood12.11 percent Cassia occidentalis leaf, 4 percent Vitex negunda leaf,, 8 percent Carea Arborea leaf, 3.33 percent Plantago major stem, 10 percent Rosa damascena flower petal, 10 percent Solanum xanthocarpum whole plant, 8 percent Solanum nigrum whole plant, 6-10 percent Pimpinella anisum seed & fruit, 6-10 percent Cuscuta reflexa stem, and 2-6 percent Cyperus scariosus whole plant. 6. A synergistic polypharmaceutical composition for treatment of viral hepatitis and jaundice substantially as herein described with reference to accompanying examples.

Documents:

1658-del-1998-abstract.pdf

1658-del-1998-claims.pdf

1658-del-1998-correspondence-others.pdf

1658-del-1998-correspondence-po.pdf

1658-del-1998-description (complete).pdf

1658-del-1998-drawings.pdf

1658-del-1998-form-1.pdf

1658-del-1998-form-19.pdf

1658-del-1998-form-2.pdf

1658-del-1998-gpa.pdf

1658-del-1998-pa.pdf