Title of Invention

"A POLYHERBAL COMPOSITION FOR THE TREATMENT OF VIRAL HEPATITIS "

Abstract A polyherbal composition for treatment of viral hepatitis which comprises a synergistic composition of an intimate mixture of seeds of Lactuca Serriola Linn,; Portulaca Oleracea Linn and, Chicorium Endivia Linn in synergistic admixture with kernels of Lagenaria Siceraria, said seeds and kernels being present in a powdered form and all the ingredients being present in an amount of from 10 to 50% by weight of said composition.
Full Text HERBAL COMPOSITION FOR THE TREATMENT OF VIRAL HEPATITIS AND DRUG INDUCED JAUNDICE
Field of the invention
'This invention relates to the anti-viral compositions. In particular, the present invention relates compositions for use in the treatment of viral hepatitis and drug induced jaundice. More particularly, the present invention relates to herbal based compositions for the treatment of viral hepatitis and drug induced jaundice/ BACKGROUND OF THE INVENTION
Hepatitis virus infection is a major health problem worldwide. HBV is a causative agent of hepatitis. More than 350 million people throughout the world are chronic carriers of HBV, Typically, the human host is unaware of infection and HBV infection leads to acute hepatitis and liver damage, jaundice and elevated blood levels of certain enzymes. Additionally, HBV contributes to the formation of hepatocellular carcinoma and is second only to tobacco as a cause of human cancer. The mechanism by which HBV induces cancer is unknown, although it has been postulated that it may directly trigger tumor development or indirectly trigger tumor formation through chronic inflammation, cirrhosis and cell regeneration associated with the infection.
HBV belongs to the genus of hepadnavirus in the hepadnaviridae family. The genome of HBV consists of circular, partially double-stranded DNA of about 3200 base pairs that code for seven viral proteins. The polymerase gene completely overlaps the viral envelope genes PreSl, PreS2 and S and partially overlaps the X and core genes. The envelope of HBV consists of three proteins and their glycosylated derivatives. The three proteins, the small (S), middle (M) and large (L), are hepatitis B surface (HBs) proteins that contain the S gene sequence. Other proteins such as the MHBs contain the PreS2 sequence.
The core gene contains the nucleocapsid protein (183-185 aa) and the hepatitis B core antigen. The precore region, upstream of the core region, consists of 87 nucleotides that codes for 29 amino acids and is in phase with the core region. The first 19 amino acids of the precore region act as a signal for membrane translocation and eventual secretion of the precore gene product, the Hbe antigen.
Although a DNA virus, HBV requires reverse transcription through the formation of a (+) strand RNA intermediate. Reverse transcriptase has poor proof-reading ability and this leads to a high rate of nucleotide mismcorporation; calculations suggest that this error-

prone replication leads to one point replacement, deletion or insertion per 1000 to 100,000 nucleotides copied.
Of the various types of hepatitis viruses, Hepatitis B and C are the deadliest. In the absence of a complete and reliable treatment, the number of carriers of these viruses are increasing every day all over the world, particularly in the Asia-Pacific region and the African countries.
The best defense to date has been vaccination. Human serum-derived vaccines, through genetic engineering, have been developed. Although the vaccine has been found effective, production has been hampered by the limited supply of human serum from chronic carriers and a long and expensive purification process. Furthermore, each batch of vaccine must be tested in chimpanzees to ensure safety. Additionally, vaccines do not help the patients already infected with the virus.
Great efforts have been made to develop clinically useful treatments for hepatitis B but they have been met with limited success. For example, interferon and several nucleoside analogs have shown relatively low cure rate of hepatitis B and they have often produced serious adverse effects. 2',3'-dideoxycytidine (ddC) has had high toxicity on the central and peripheral nervous system. Another nucleoside analog, ara-AMP, was found to transiently suppress HBV infection but also has been shown to be extremely toxic as well. Prior art is replete with teachings of allopathic and chemical treatment of hepatitis. Most of these treatments are however to manage the symptoms and one can never be sure if the patient will recover completely. Thanks to the self-limiting nature of these viruses, almost sixty percent of the patients recover automatically. Yet, a very large number of patients die every year. DESCRIPTION OF PRIOR ART
Of late there has been a shift in focus towards herbal based compositions for treatment of hepatitis infections. Thus, U.S. Patent No. 6,113,909 discloses a herbal composition which comprises as an active Ingredient a mixed extract, specifically mixed aqueous or alcoholic extract, obtained from a mixture of Phellodendron amurense RUPRECHT cortex and Patrinia scabiosaefolia FISCH. However, while this composition particularly, exhibits a direct anti-viral activity against hepatitis C virus in chronic hepatitis C and in the primary stage of hepatic cirrhosis it is not suited for treatment of other hepatitis infections. At the same time, this composition reduces inflammation and potentiates the activity of T helper cells involved in the host immune system.
U.S. Patent No. 5,648,089 discloses another herbal based composition for the treatment of viral hepatitis infections. The herbal combination according to the U.S. Patent

comprises a mixture for oral administration of the following dried plants in the following ratio, all percentages being percent by weight of the mixture:
(a) 40 percent from the dried fruit of Phyllanthus Embilca L.;
(b) 10 percent from the dried fruit of Terminalia Chebiola RETZ;
(c) 7 percent from the plant Cichorium Intyus L., excluding the roots;
(d) 10 percent from the flower of the plant Carthamus Tincorius L.
(e) 3 percent from the plant Solenostemma Argel Hayne, excluding the roots,
(f) 10 percent from the seeds of Nigella Sativa L.;
(g) 5 percent from the plant Erythraea Centaurium Pers, excluding the roots;
(h) 10 percent from the stem and leaves of the plant Cynara Cardunculus Var. Scoly; and (i) 5 percent from the rhisome (stems) of Rheuon officinale Baill.
According to the above U.S. Patent, this Group of herbs have been a part of folk medicine and traditional medicine used for other ailments individually but never with the following arrangement and combination for a treatment of Hepatitis-C and Hepatitis-B disease. They also are used in combination with the liquid extract of one more herb in a special fashion, (regimen). The U.S. Patent however, reports the use of this herbal combination only for the treatment of hepatitis B and C and not other forms of viral hepatitis.
Also, this composition has to be taken alongwith nasal drops of a separate herb that was used with the other combination for treating patients diagnosed with active Hepatitis-B and patients diagnosed with active Hepatitis-C, which makes it slightly patient unfriendly.
U.S. Patent No. 6,136,316 granted to Dabur Research Foundation gives an excellent disclosure on a polyherbal composition for treatment of hepatitis infections. This patent also discloses a highly informative teaching related to hepatitis in general. According to this patent, the Ayurvedic system of Indian traditional medicine provides many formulations for treating many liver disorders/diseases in human beings and animals. Majority of these plants have already been investigated for their beneficial medicinal properties (Chopra, Nadkarni).
The following are excerpts from said U.S Patent No. 6,136,316:
Rheum emodi Wall: Rheum emodi Wall is grown in sub Himalayan regions of India and its neighbouring countries. The traditional preparation consists of dried rhizome of the plant and roots which are cut into pieces and dried. Rhubarb root contains a large proportion of Chrysophanic acid, sometimes called Chrysophan. An allied substance Emodin, a glucose rhapantiein, a tannin named Rheo tannic acid, several resins, an

albuminoid principle, mucilage, extractives, tannic and gallic acids, sugar, starch, pectin, lignan, calcium oxalate and various inorganic salts.
Phyllanthus amarus Linn (niruri): Phyllanthus amarus Linn (niruri) is a herbaceous plant which occurs as a winter weed throughout the hotter parts of India. The plant is bitter and astringent in taste, and the extract of the roots and the leaves are used as a remedy for jaundice and other related liver disorders. Eclipta alba Hassk: Eclipta alba Hassk is a herbaceous plant which grows in moist conditions throughout India. The extracts of Eclipta alba Hassk are largely used for the treatment of the liver, and the gall bladder diseases. The plant juice and extracts are also used in combination with other aromatics in the treatment of jaundice.
Andrographis paniculate Nees: Andrographis paniculate Nees is an annual herb which is grown as a hedge plant throughout the plains of India. The plant is reputed in the Ayurvedic system of medicine to be useful in the treatment of sluggish liver and jaundice.
Picrorrhiza kurroa Royle ex Benth: Picrorrhiza kurroa Royle ex Benth is a perennial herb found in the Alpine Himalayas from Kashmir to Sikkim. Its use in the Ayurvedic system of medicine is described in the disease states of jaundice, liver disorders and urinary disorders.
Fumaria officinalis Linn: Fumaria officinalis Linn is reputed to be useful in disorders of the liver, and is found throughout India, from the Indo-gangetic plain to the Nilgiri Hills.
Tinospora cordifolia Miers: Tinospora cordifolia Miers is a succulent climbing shrub and occurs in most pars of Southern India. The extracts of T. cordifolia Miers are effective in promoting the regeneration of liver tissue, and preventing fibrous changes occuling due to hepatotoxic injuly to Liver.
Terminalis chebula Retz: The fruits of this large deciduous tree are used for its purgative, tonic and carminative properties. In combination with Embellica officinalis and Terminalia belerica, under the Indian name TREPHALA, these fruits are used as adjuncts to other medicines in the treatment of almost all disease states in the Ayurvedic system of medicine.
Cichorium intybus Linn: Cichorium intybus Linn is a rough and glandular perennial herb found throughout northwest India. The root of the plant is known to be useful in the disease states resulting in enlargement of liver and spleen.

Tephrosia purpurea Linn: The root of this branched herbaceous plant has been found to be useful in the treatment of sluggish liver by improving its function and also in enlarged spleen. HEPATITIS VIRUSES
Acute hepatitis is usually viral in origin and is a diffuse necro-inflammatory disease of the liver as a result of infection by primary seven hepatotropic viruses namely hepatitis A (HAV), Hepatitis B (HBV) parenterally transmitted non-A non-B hepatitis (HEV), hepatitis F (HFV) and hepatitis G (HGV).
The only way of gradually eradicating the infection is by (1) active universal immunisation in childhood and/or (2) development of treatment modalities for persistently infected persons. Therapeutic studies conducted over the past 15-20 years had only marginal success once the infection is establishede (Hoofnagle, 1991). Several compounds, such as interferon, adenine arabinoside, acyclovir, ganciclovir, zidovudine and immunomodulatory regime administered alone or in combination have been evaluated. Most of these agents have transient effects on viremia, with rebound occurrence on withdrawal of drug. Significnt toxicity have also been observed with long term therapy. Hepatitis Virus Infection and Natural Plant Products
Many plant products have been in use in the treatment of liver diseases since time immemorial. In Indian systems of medicine, natural plant products have been used in the treatment of jaundice and liver disorders. The use of various plants have been described in ancient Indian Ayurvedic literature.
In South India, the plants of genus Phylianthus and Eclipta alba Hassk are commonly used as a traditional treatment for clinical jaundice including that of viral hepatitis and are commercially available (Thyagarajan, 1986; Thyagarajan & Jayaram, 1992). Phylianthus species are also used in China, the Philippines, Cuba, Nigeria, Guam, East and West Africa, the Carribean, Central America and South America. The above two plants have been recently evaluated for their action on Hepatitis B virus. The first screening strategy used was to test the ability of plant extract to coat viral HBsAg, and thereby inhibit the reaction with antibody to HBsAg (anti HBs like activity) (Unander and Blumberg, 1991; Blumberg et al., 1990). The rationale was that such an inhibition might have effect on pathogenesis of Hepatitis B virus in vivo in man (Mehrotra et al., 1990, 1991). This observation was also supplemented by the ability of plant extract to inhibit DNA polymerase (DNAp) of Hepatitis B virus in vitro.

The crude extracts of Eclipta laba Hassk when mixed with HBsAg brings about its interaction, thereby suggesting the presence of anti HBs like activity (Thyagarajan el al., 1982).
The extracts of Phyllanthus niruri Linn now known as Phyllanthus amarus Linn inhibit human HBV-DNAp as well as HBsAg and anti HBs interaction. Also, the closely related, animal hepadna viruses, e.g. Woodchuck hepatitis virus, and duck hepatitis B virus are also affected by P. amarus Linn (Blumberg et al., 1990). In a series of studies on long term carriers of woodchucks infected with woodchuck hepatitis B virus it was observed that the P. amarus Linn extract generally eliminates or decreases the level of virus (Venkateshwaran et al., 1987; Venkateswaran and Blumberg-U.S. Pat. No. 4673575, 1987). However, subsequent studies using another animal model of Human Hepatitis B virus, Duck hepatitis B virus failed to confirm the findings reported earlier [Nitu et al., 1990; Munshi et al., 1993(a);(b)].
Clinical studies in humans using P. amarus Linn, on Hepatitis B virus has also been carried out. In 1988, it was reported from Madras, India that dried milled P. amarus Linn was successful in clearing Hepatitis B surface antigen from 59% carriers of Hepatitis B virus (Thyagarajan el al., 1990). However, this observation was followed by another report wherein the success rate of treatment with P. amarus Linn was reduced to 20% (Thyagarajan et al., 1990). In subsequent clinical studies on Hepatitis B virus carriers with P. amarus Linn, results were not reproducible by other workers in different other countries (Brook, 1988; LeeLarasamee et al., 1990; Mei-Xia et al., 1991; Milne et al., 1993).
Traditional plant medicines have also been tested for suppression of viral antigen secretion by Alexander Cell line obtained from human hepatocellular carcinoma (PLC/PRF/5), which contain several integrated copies of HBV genome and produces small amount of HBsAg apparently in the form of 22 nm particles. Goto et al. (1996) using the above cell line as a model tested forty three (43) extracts of different herbal medicines for suppression of secretion of HBsAg in vitro. Of the various extracts, Rheum palmatum L also suppressed the secretion of HBsAg. However, the above observation is never substantiated/established in any in-vivo animal model of Hepatitis B virus infection and also in human studies.
With the above background U.S.Patent No. 6,136,316 discloses a Rheum emodi based polyherbal composition for the treatment of hepatitis B and hepatitis E. However, there is still a need for a herbal composition which is effective universally in the treatment of all kinds of viral hepatitis.

OBJECTS OF THE INCVENTION
Accordingly, it's a principal object of the present invention to provide a composition for use against the treatment of all kinds of viral hepatitis infection.
It is another object of the present invention to a composition for the treatment of viral hepatitis that ensures complete recovery.
. It is yet another object of the present invention to provide a composition for the treatment of viral hepatitis which makes the patient seo-negative at the end of the treatment period.
Another object of the present invention is to provide a composition for treatment of acute hepatitis caused by Hepatitis E virus, a super infection due to Hepatitis E virus in healthy Hepatitis B carrier state in man.
Another object of the invention relates to a method of regenerating and protecting the liver cells from necrosis by using polyherbal composition of the present invention.
Another object of the invention relates to a method of treating acute Hepatitis E virus infection,healthy hepatitis B carriers with superadded Hepatitis E virus and carriers of Hepatitis B virus.
Yet another object of the present invention is to provide a method of treating acute and chronic viral Hepatitis and theraptic effects of hepatitis B virus infection.
One more object of the invention relates to a method treating acute liver failure cause due to hepatitis virus infection and a method of protecting liver cells against known chemicals/durgs which cause liver injury.
Another important object of the present invention is to provide a polyherbal pharmaceutical composition which is safe without any toxic effects, also provides hepatoprotection in acute hepatotoxicity produced by known hepatotoxins in animals including human beings. SUMMARY OF THE INVENTION
The above and other objects of the present invention are achieved by the novel and synergistic composition of the present invention based on the extracts obtained from the seeds of Lactuca Serriola Linn,; Portulaca Oleracea Linn., Chicorium Endivia Linn., and Lagenaria Siceraria.
Accordingly, the present invention provides a polyherbal composition for treatment of viral hepatitis which comprises a synergistic composition of an intimate mixture of seed of Lactuca Serriola Linn,; Portulaca Oleracea Linn., Chicorium Endivia Linn in synergistic admixture with kernels of Lagenaria Siceraria, said seeds and kernels

being present in a powdered form and all the ingredients being present in an amount for from 10 to 50% by weight of said composition.
In a preferred embodiment, said seeds of Lactuca Serriola Linn,; Portulaca Oleracea Linn, and Chicorium Endivia Linn are present in equal proportions.
In another embodiment, the amount of said kernels of Lagenaria Siceraria is about one fourth the volume of the total combined volume of said powdered seeds of Lactuca Serriola Linn,; Portulaca Oleracea Linn, and Chicorium Endivia Linn.
In a preferred embodiment the composition of the invention is in admixture with a pharmaceutically accepted vehicle or an adjuvant.
The present invention also discloses a method for the preparation of a polyherbal composition for treatment of viral hepatitis which comprises mixing seeds of Lactuca Serriola Linn,; Portulaca Oleracea Linn, and Chicorium Endivia Linn, powdering said mixture of seeds to form a first powder, powdering kernels of Lagenaria Siceraria to form a second powder, intimately mixing said first and second powder to produce said composition.
Preferably, said seeds are thoroughly washed and sieved prior to powdering.
In a preferred embodiment, said amount of each ingredient of the composition is from 10 to 50% by wt of the total composition.
In another embodiment, each said components of the composition are present in equal proportions. DETAILED DESCRIPTION
The polyherbal composition of the present invention is based on the following:
1. Lactuca Serriola Linn, (seeds)
2. Portulaca Olereacea Linn, (seeds)
3. Chicorium Endivia (seeds)
4. Lagenaria Siceraria (seed's kernels)
The composition of the present invention based on the above seeds acts as a synergistic composition having unexpected and new properties in the treatment of viral hepatitis. To the applicant's knowledge, none of the above-mentioned substances is reported to have any efficacy against viral hepatitis. The combination of above-mentioned substances in the treatment of viral hepatitis is therefore, truly inventive and non obvious.
To prepare the composition of the present invention, the ingredients are first thoroughly washed and dried well. Thereafter they are sieved to remove remaining impurities and preferably, washed again with sterile water. Components 1 to 3 above are mixed together and powdered by any conventional means. In a preferred embodiment,

components 1 to 3 are present in equal proportions although this is more for convenience than performance.
The invention works as long as all the three components are present. The component 4 is also powdered and intimately mixed with the mixture of components ] to 3. In a preferred embodiment, the amount of component 4 is one fourth the volume of the mixture of components 1 to 3. The medicine is now ready for use.
The ideal dosage of the medicine is preferably one teaspoon three times day. The patients are conveniently administered the medicine after breakfast, lunch and dinner. One teaspoon contains approximately 2.5 gms of "the medicine. Treatment is continued till complete recovery. Patients are monitored by having their liver function test performed once every fortnight.
It has been observed that complete recovery is achieved in about 98% of the cases. All the patients whose liver function tests become normal also become sero-negative. Since the patients become sero-negative, the sequelae in the form of liver-cirrhosis and primary hepato cellular carcinoma is also completely ruled out since the patients are no longer carriers. The average period of complete recovery is about ninety days in case of hepatitis B and about forty days in case of other types of acute viral hepatitis.
The present invention will now be described with reference to the following Examples which are solely for the purposes of illustration of the invention.
Example 1
Preparation of the composition of the invention
Seeds of Lactuca serriola Linn, Portulaca oleracea Linn and Chicorium endivia Linn are taken in approximately equal proportions. They are sieved, washed and sieved again. The washing and serving steps may be carried out many times. The mixture of said seeds are then pulverised and powdered by any conventional technique. Thereafter, kernels extracted from the seeds of Lagenaria siceraria. The kernels are powdered and intimately mixed with the powdered mixture obtained above.
Example 2
Effect of composition of the present invention on patients suffering from viral
hepatits
PVV& patients suffering from acute viral hepatitis were selected at random. Liver function tests were performed. The results of liver function tests are shown in Table 1.

The patients were administered the composition produced in Example 1 for three months. The dosage was one teaspoon of the composition, three times a day. The liver function tests were carried out periodically. The results of liver function tests after approximately three months are shown in Table 2.
From the comparative results contained in Tables 1 and 2 it becomes clear that the composition of the present invention is extremely effective in the treatment of viral hepatitis and at the end of the treatment period, the liver function tests of the patients are quite normal.
(Table Removed)



I Claim:
1. A polyherbal composition for treatment of viral hepatitis which comprises a synergistic composition of an intimate mixture of seeds of Lactuca Serriola Linn,; Portulaca Oleracea Linn and, Chicorium Endivia Linn in synergistic admixture with kernels of Lagenaria Siceraria, said seeds and kernels being present in a powdered form and all the ingredients being present in an amount of from 10 to 50% by weight of said composition.
2. A composition as claimed in claim 1 wherein said seeds of Lactuca Serriola Linn,; Portulaca Oleracea Linn and Chicorium Endivia Linn are present in equal proportions.
3. A composition as claimed in claim 1 or 2 the amount of said kernels of Lagenaria Siceraria is about one fourth the volume of the total combined volume of said powdered seeds of Lactuca Serriola Linn,; Portulaca Oleracea Linn and Chicorium Endivia Linn.
4. A composition as claimed in any preceding claim in admixture with a pharmaceutically accepted vehicle or an adjuvant.
5. A polyherbal composition for treatment of viral hepatitis substantially as herein described with reference to and as illustrated in the foregoing examples.

Documents:

0858-del-2004-abstract.pdf

0858-del-2004-claims.pdf

0858-del-2004-correspondence-others.pdf

0858-del-2004-description (complete).pdf

0858-del-2004-form-1.pdf

0858-del-2004-form-18.pdf

0858-del-2004-form-2.pdf

0858-del-2004-form-3.pdf

858-DEL-2004-Abstract-(16-09-2008).pdf

858-DEL-2004-Claims-(16-09-2008).pdf

858-DEL-2004-Correspondence-Others-(05-05-2010).pdf

858-DEL-2004-Correspondence-Others-(07-07-2009).pdf

858-DEL-2004-Correspondence-Others-(12-08-2008).pdf

858-DEL-2004-Correspondence-Others-(16-09-2008).pdf

858-DEL-2004-Correspondence-Others-(22-06-2010).pdf

858-DEL-2004-Form-1-(16-09-2008).pdf

858-DEL-2004-Form-2-(16-09-2008).pdf

858-DEL-2004-Form-3-(12-08-2008).pdf


Patent Number 247615
Indian Patent Application Number 858/DEL/2004
PG Journal Number 17/2011
Publication Date 29-Apr-2011
Grant Date 27-Apr-2011
Date of Filing 11-May-2004
Name of Patentee OHARI, VIJAY KUMAR
Applicant Address 279/98 PANDARIBA, LUCKNOW-226004, UTTAR PRADESH, INDIA.
Inventors:
# Inventor's Name Inventor's Address
1 OHARI, VIJAY KUMAR 279/98 PANDARIBA, LUCKNOW-226004, UTTAR PRADESH, INDIA.
PCT International Classification Number A61K 35/00
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA