DYSFUNCTION

FIELD OF INVENTION :

[0001 ] The present invention relates to a new plant extract composition comprising extracts of Curcuma longa, Gymnosporea Montana, Solanum nigrum and optionally at least one carrier. The plant extracts composition of the present invention is used for treatment and/or prevention of the conditions of liver dysfunction. The present invention also relates to processes for preparation of the composition.

BACKGROUND OF THE INVENTION

[0002] Liver of a human's body is an organ which acts like a filter. It helps digest food by filtering out bad chemicals and substances from the food we eat and forms an energetic and critical part of our digestive system, making it one of the most important organs in our body. However, the liver is also prone to damage and there are many causes of damage to the liver, which range from chemicals to diseases.

[0003] At present, near about two million Americans suffer from liver damage caused by alcohol abuse. About 10 to 20 percent of large alcohol takers develop cirrhosis of liver, which is characterized by scarring of the liver and causes irreversible damage. If large alcohol takers do not stop drinking, cirrhosis can cause poor health and, ultimately, death. In addition to cirrhosis, heavy drinkers may suffer from chronic liver disease or alcoholic hepatitis. [0004] Damage to liver can lead to problems with blood sugar levels. When alcohol is present in the body, the liver works to metabolize it. Because the liver is busy metabolizing alcohol, it is often not able to adequately maintain blood sugar levels, which may result in hypoglycemia (low levels of blood sugar). Hypoglycemia is most likely to occur in individuals do not maintain an adequate diet. When Hypoglycemia occurs, the brain is not able to receive the energy that it needs to function, and symptoms such as hunger, weakness, headache, tremor, and even coma (in severe cases) may occur.

[0005] Hepatic insufficiency can be defined as a clinical condition resulting from additive effects of toxic metabolic defects. It may occur in any form of liver disease. It is usually gradual and relatively asymptomatic (David Cayer, American journal of digestive disease).

[0006] Hepatic insufficiency can be characterized by a condition where liver is unable to perform its normal function. If the insufficiency is not treated, it may lead to an impaired function of filtration carried out by the liver and as a result, waste products can get accumulated in the blood leading to a serious condition of hepatic coma.

[0007] Jaundice is a clinical condition which is characterized by yellowing of skin and whites of the eyes which is due to an accumulation of a cellular waste production called bilirubin. The discoloration is often, but by no means always, accompanied by itching, which can be intense, as well as by nausea, vomiting, headache, fever, dark-colored urine, abdominal pain, loss of appetite, abdominal swelling, and light-colored stools.

[0008] Jaundice is not a disease in and by itself, but is a sign that the liver is having inability to perform the normal function of handling bilirubin. Liver makes bilirubin from dying red blood cells and other sources. It then converts bilirubin into bile, which has several purposes, among them being digestion of fatty acids and neutralization of stomach acid. If there is too much bilirubin production for the liver to deal with, or if liver's functioning is compromised, jaundice is the outcome.

[0009] Jaundice may be caused by several different disease processes. It is helpful to understand the different causes of jaundice by identifying the problems that disrupt normal bilirubin metabolism and/or excretion.

[00010] Liver has many functions with one function being to produce and secrete bile into the intestines to help digest dietary fat. Another function is to remove toxic chemicals or waste products such as bilirubin from the blood. Liver removes bilirubin from the blood. After bilirubin enters the liver cells, the cells conjugate (attaching other chemicals, primarily glucuronic acid) to the bilirubin, and then secrete the bilirubin/glucuronic acid complex into bile. The complex that is secreted in bile is called conjugated bilirubin. Conjugated bilirubin is eliminated in the feces. (Bilirubin is what gives feces its brown color.) Conjugated bilirubin (called direct) is distinguished from the bilirubin that is released from the red blood cells and not yet removed from the blood, which instead is termed unconjugated (called indirect) bilirubin.

[00011] Jaundice occurs when there is 1 ) too much bilirubin being produced for the liver to remove from blood. (For example, patients with hemolytic anemia have an abnormally rapid rate of destruction of their red blood cells that releases large amounts of bilirubin into blood), 2) a defect in the liver that prevents bilirubin from being removed from blood, converted to bilirubin/glucuronic acid (conjugated) or secreted in bile, or 3) blockage of the bile ducts that decreases the flow of bile and bilirubin from the liver into intestines. (For example, the bile ducts can be blocked by cancers, gallstones, or inflammation of the bile ducts). The decreased conjugation, secretion, or flow of bile that can result in jaundice is referred to as cholestasis: however, cholestasis does not always result in jaundice.

[00012] Bile ducts normally discharge pigments and bile salts into the intestine and an obstruction in the ducts can cause jaundice. The yellowish pigmentation of the skin is because of bile mixing with the blood. An obstruction could be caused by gallstones or inflammation of the liver, known as hepatitis.

[00013] Results and statistical analysis of many epidemiological studies, clinical trials, and laboratory mechanistic studies indicate that many medicinal plants may be useful in the prevention and treatment of liver dysfunction and its related diseased conditions.

[00014] There are many poly herbal formulations available in the market claiming to be useful for many medical conditions including liver damage, liver cirrhosis, hepatic insufficiency and many more but a majority of such poly herbal formulations don't contain standardized material and appropriate proportion of required plant extract with required active constituents according to targeted condition.

[00015] It is visible from the above discussion that there still exists a long felt need and a strong demand for herbal formulations based on plants of natural kingdom, which provide beneficial activity against liver dysfunctional and at the same time don't have major side effects to human beings. IMPROVEMENTS AND/OR MODIFICATIONS FROM THE MAIN INVENTION

[00016] The main (parent) invention as described in 153/MUM/201 1 relates to a plant extracts composition comprising extracts of Curcuma longa, Phyllanthus emblica, Gymnosporea Montana, and at least a carrier for the treatment of liver dysfunction.

[00017] The inventor had continued his further research and found a new plant extracts composition comprising extracts of specific plant parts of Curcuma longa, Gymnosporea Montana and Solanum nigrum in specific weight percentages, which has shown marked improvement in clinical efficacy against liver dysfunction. The results are shown in "Detailed Description" Section of the Specification. The new plant extracts composition optionally contains at least one carrier.

[00018] The inventor has added a new ingredient Solanum nigrum which contains high value of beta 1 secretion as well as Vitamin C, which can modify pathophysiological factor more potentially. Further, the new composition does not contain an extract of Phyllanthus emblica (as contained in the Parent Application) as the same is not required while adding Solanum nigrum.

[00019] Furthermore, the plants extract composition of the present invention has shown an efficacy in case of Diabetes Mellitus as well addition to anti-hepatic activity. OBJECTS OF THE INVENTION

[00020] The main object of the present invention is to provide a new plant extract composition for the treatment and/or prevention of the conditions of liver dysfunction.

[00021 ] It is another object of the invention to provide a new plant extracts composition which can modify the pathophysiological factor more potentially; comprising extracts of specific plant parts of Curcuma longa, Gymnosporea Montana, Solanum nigrum in specific weight percentages.

[00022] It is yet another object of the present invention to provide processes for preparing the plant extracts composition.

SUMMARY OF THE INVENTION

[00023] The present invention provides a new plant extracts composition comprising extracts of specific plant parts of Curcuma longa, Gymnosporea Montana and Solanum nigrum in specific weight percentages.

[00024] The plant extracts composition of the present invention can optionally contain at least one carrier.

[00025] Extracts used to prepare the composition are prepared from specific parts of the plants; for example, extracts of Curcuma longa, Gymnosporea Montana and Solanum nigrum are prepared from tubers, leaves and fruits of respective plants. DETAILED DESCRIPTION OF THE INVENTION

[00026] The present invention contemplates a new plant extracts composition comprising extracts of specific plant parts of Curcuma longa, Gymnosporea Montana, Solanum nigrum in specific weight percentages, and optionally at least one carrier.

[00027] In an embodiment, the present invention provides a plant extracts composition comprising 10-25 % w/w extract of Curcuma longa, 50-70 % w/w extract of Gymnosporea Montana and 40-50 % w/w extract of Solanum nigrum for use in treatment and/or prevention of liver dysfunction.

[00028] As used herein, liver dysfunction means a disease condition known as jaundice and hepatic insufficiency.

[00029] Active compound responsible for specific therapeutic activity can be found in higher concentrations in specific parts of medicinal plants and in lower concentrations in other specific parts. Specific part of a medicinal plant having higher concentration is selected and processed for preparing the plant extract composition. Preferably, extracts of specific parts of plants are used for preparation of the composition of the present invention, wherein the composition comprises high value of beta 1 secretion besides having vitamin C, which is beneficial to modify pathophysiological factor more potentionally and provide desired therapeutic effect in liver dysfunction condition.

Curcuma longa:

[00030] Curcuma Longa is a small perennial herb native to India bearing many rhizomes on its root system which are the source of its culinary spice known as Turmeric. Extract of tuber part of Curcuma long containing 95% of active ingredient Curcumin is used for the preparation of the present invention.

Botanical Classification:

• Family: Zingiberaceae

• Genus: Curcuma

• Species: Longa

Gymnosporea montana:

[00031] Gymnosporea montana is a traditional herbaceous plant of Celastraceous family found in different regions of India. In vernacular language it is called as Vikalo. Extract of leaves of Gymnosporea montana containing Alkaloid as active ingredient is used for the preparation of the present invention. Botanical Classification:

• Family: Celastraceae

• Genus: Gymnosporea

• Species: Montana

Solanum nigrum:

[00032] Solanum nigrum is a fairly common herb or short-lived perennial shrub of Solanaceae family. Its vernacular name is Makoi in Hindi. Extracts of fruits of Solanum nigrum containing Alkaloid and bitter as active ingredients is used for the preparation of the present invention.

Botanical Classification:

• Family: Solanaceae

• Genus: Solanum • Species: S. nigrum

[00033] Extracts of different parts of above mentioned herbal plants are used in form of a dried powder, which facilitates preparation of present plant extracts composition.

[00034] The plant extracts composition of the present invention can be administered orally. Dosage form of the plant extracts composition can be selected from a group comprising of tablet, capsule, powder, beads, pellets, granules, solution, syrup, suspension, oleoresin, and emulsion. A preferred dosage form is one of a tablet, capsule, powder, syrup, or granule. More preferably, the dosage form is one of a capsule, tablet, or syrup.

[00035] The plant extracts composition of the present invention can be prepared by using any common technique available in the art.

[00036] The plant extracts composition of the present invention comprises

10-25 % w/w extract of Curcuma longa, 50-70 % w/w extract of Gymnosporea

Montana and 40-50 % w/w extract of Solanum nigrum.

[00037] The plant extracts composition of the present invention optionally contains at least one carrier. The carrier as used herein is selected from a group comprising of diluent, binder, disintegrant, glidant, and lubricant. There may be one or more carriers used in the preparation of composition.

[00038] Diluents are inert excipients that are used to adjust the bulk in a pharmaceutical composition. Commonly used diluents comprise of lactose, dicalcium phosphate, micro crystalline cellulose, kaolin, mannitol and starch. In an embodiment, Diluents can be used in a range of 2 to 5 % w/w of the composition. [00039] Binders are utilized in a pharmaceutical composition to impart cohesive force to the composition powder, which allows the powder materials to retain their integrity once they are compressed. Commonly used binders comprise of carboxymethyl cellulose, methyl cellulose, polyvinylpyrrolidone, ethyl cellulose, pregelatinized starch, and gelatin. In an embodiment, binders can be used in a range of 1 to 5 % w/w of the composition.

[00040] Disintegrant is an excipient or a mixture of excipients added to facilitate breakup of binded powdered materials forming the composition. Dried and powdered corn starch or potato starch are widely used disintegrants. These disintegrants have a good affinity towards water and swell when moistened, and result in rupturing the tablet. A group of materials known as super-disintegrants comprising croscarmelose, cross-linked cellulose, crosprovidone, cross-linked polymer, sodium starch glycolate, and cross-linked starch can be used in the composition. In an embodiment, disintegrants can be used in a range of 2 to 5 % w/w of the composition.

[00041] Lubricants are used in a pharmaceutical composition to prevent adhesion of a tablet material to the surface of dyes and punches. Commonly used lubricants comprise of magnesium stearate, calcium stearate, talc, stearic acid, hydrogenated vegetable oils, and PEG. In an embodiment, the lubricants can be used in a range of 0.5 to 4 % w/w of the composition.

[00042] Glidants are used in a pharmaceutical composition to improve flow characteristics of powder materials. Colloidal silicon dioxide and anhydrous silica are commonly used glidants. Talc may serve as a combined lubricant/glidant. Glidants can be used in a range of 0.5 to 5 % w/w of the composition. [00043] In an embodiment, compounds/extracts procured from different plant parts are then also tested for standard laboratory analytical tests as TLC, Identification, MS., Assay by Spectrophotometer, Heavy Metals, and Microbial Profile.

[00044] Plant extracts composition of the present invention can be prepared by techniques commonly available in the art.

[00045] An exemplary and generalized process for preparing the plant extracts composition of the present invention is described below in a stepwise manner.

a) Sifting extracts of Curcuma longa, Solanum nigrum, and Gymnosporea montana through 20# and optionally Sifting at least one carrier through 40# and;

b) Mixing the sifted extracts of step a) and optionally;

c) Granulating the mixed sifted extracts of step b) using a solvent and optionally;

d) Drying granules formed from step c) and optionally;

e) Sifting dried granules of step d) through 20# and optionally;

f) Mixing materials of step b) or e) with the carrier from step a);

g) Again mixing in homogenizer for more precise mixing of molecular particles; and

h) Filling of material of step g) into capsules or compressing into tablets.

[00046] Processing steps such as sifting, granulation, drying, mixing and filling of capsule or tablet compression, as described above, can be performed as per well known techniques available in the art. [00047] A further embodiment of the present disclosure provides use of the plants extracts composition of the present invention for treating and/or preventing signs and symptoms of liver dysfunction, comprising administering to a subject in need thereof, a therapeutically effective amount of the plant extracts composition of the present invention.

[00048] The term "subject" used herein refers to mammals, most preferably humans.

[00049] Further the plants extract composition of the present invention has surprisingly shown efficacy in case of Diabetes Mellitus.

EXAMPLES

[00050] The present invention is further explained in the form of following examples. However it is to be understood that the foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.

Example 1 : Capsule composition

Procedure: Extracts of Curcuma longa, Gymnosporea Montana, Solanum Nigrum and colloidal silicon dioxide are sifted through 40#. All the sifted materials are mixed for 5 minutes. The mixed materials are filled in hard gelatin capsule of appropriate size.

Procedure: Extracts of Curcuma longa, Gymnosporea montana, Solanum nigrum, lactose anhydrous and sodium starch glycolate are shifted through 40#. All the shifted materials are mixed for 5 minutes. The mixed materials are granulated with binder solution of povidone prepared in purified water. The granules are dried and sifted through 20#. Dried granules are mixed with magnesium stearate and colloidal silicon dioxide which are sifted through 40#. The lubricated granules are compressed using appropriated punch tolling.

Example 2: Safety and Toxicity Study

Safety and efficacy/toxicity study has been carried out by LD50 test on plant extracts composition of the present invention with conventional treatment against liver dysfunction condition.

LD50 (abbreviation for "Lethal Dose, 50 %") of a toxin, radiation, or pathogen is the dose required to kill half the members of a tested population after a specified test duration. LD50 figures are frequently used as a general indicator of a substance's acute toxicity. LD50 is usually expressed as the mass of a substance administered per unit mass of a test subject, such as grams of substance per kilogram of body mass.

A group of 10 Albino mice weighing between 18 to 22 Gms was used for each dose level. All dilutions were made in sterile distilled water for injection with the plant extract composition of the present invention. All doses were given orally. The animals were observed for any mortality during seven days after the doses. After 7 days, oral LD50 in albino mice was calculated by graphical method and the results are mentioned in Table 1 .

Parameters evaluated are dilution, dose/mouse, dose/kg, log dose, % mortality. The result shows Oral LD50 in mice calculated by graphical method comes out to be 33.88gm/kg after the administration of the composition of the present invention (Example 1 )

Table 1 : Results after LD50 Test in mice

Period Dilution Dose/Mouse Dose/kg Log Dose % Mortality

16/05/11 1 gm-lOml lOOmg 5gm 0.6989 0%

To 2 gm-lOml 200mg lOgm 1.0000 0%

4 gm-lOml 400mg 20gm 1.3010 0%

23/05/11 8 gm-lOml 800mg 40gm 1.6020 60%

Example 3: Clinical Evaluation

Total 20 patients with liver dysfunction condition were involved in the trial and were given the treatment with the plant extract composition of the present invention (Example 1 ) twice or thrice a day as per the condition of the patient and after the treatment, patients were evaluated based on the pathological parameters and the results are mentioned in Table 2.

Parameters evaluated are total bilirubin, SGPT, urine bile salts and urine bile pigments.

Results show significant improvement in the condition of patient after plant extracts composition was administered.

Dosage regimes were one to two capsules twice or thrice a day as per the diagnostic condition of the patient for ten days for all patients.

Table 2: Results after treatment with the composition of the present invention: Sr. Patient Normal: Direct : 0.2-1.0 - lndirect:0.0-0.8 -S.G.P.T: 0.45 Urine Bile Salts: Complaints Observation No. Code Absent-Urine bile Pigments: Absent of the composition

Age/ Total Direct Indirect S.G.P.T Urine Urine Bile

of the present Sex (mg/dl) (mg/dl) (mg/dl) (μ/L) Bile Pigments

invention

Salts

(Example 1)

1 RT 14/M 6.8 5.8 1 1550 Loss of appetite

& Vomiting

Example 1 2.2 2 0.2 80 Nil Symptomatic

Relief

2 AP 27/M 12.8 9.4 3.4 2520 Vomiting &

Nausea

Example 1 3.8 2.5 1 .3. 390 Mild Gut Symptomatic disturbance Relief

3 SK 25/F 9.2 6.8 2.4 2440 Weakness,

Vomiting, Back

pain

Example 1 4 3.1 0.9 280 Nil Symptomatic

Relief

4 DP 21 /M 4 3 1 1870 Vomiting,

Uneasiness

Example 1 2.1 1.3 0.8 190 Nausea Symptomatic

Relief

5 DJ 7/M 3.3 2.3 1 1900 Vomiting,

Uneasiness,

Weakness

Example 1 1.9 1 0.9 160 Nil Symptomatic

Relief

6 PN 20/F 9 8 1 2550 Vomiting,

Headache,

Chest pain

Example 1 1.8 1 0.8 330 Nausea Symptomatic

Relief

7 MV 40/M 12.4 11 1 .4 2140 Vomiting

Bodyache

Example 1 5.5 3.2 2.3 102 Nil Symptomatic

Relief

8 DP 20/F 10.5 9.4 1 .1 84 Vomiting, Fever,

Back pain

Example 1 3.1 2.4 0.7 21 Mild-Gut Symptomatic

Disturbance Relief

9 DV 26/M 12.5 2.8 9.7 2100 Chest Pain,

Vomiting,

Weakness, Bodyache

Example 1 2.8 1.9 0.9 170 Nil Symptomatic

Relief

RS 33/M 7.8 6.8 1 2080 Nausea, Neck

pain

Example 1 1.7 1.3 0.4 510 Nil Symptomatic

Relief

DZ 35/M 10.34 8.48 1 .86 1500 Vomiting,

Bodyache

Example 1 1.55 0.78 0.77 40.18 - - Nil Relief

PP 45/M 9.89 8.12 1 .77 2500 Nausea,

Vomiting

Example 1 1.22 0.66 0.56 36.12 - - Nil Relief

FM 30/F 11 .34 9.98 1 .36 1700 Weakness,

vomiting,

bodyache

Example 1 1.56 0.89 0.67 45.48 - - Gut Disturbance Relief

VV 28/M 10.98 9.14 1 .84 1700 - - Vomiting, fever Relief

Example 1 2 1.12 0.88 55.18 - - Nil Relief

DR 8/M 8.94 7.66 1 .28 2100 - - Fever, vomiting

Example 1 1.45 0.88 0.57 51 .58 Nausea Symptomatic

Relief

RK 27/M 9.14 7.94 1 .2 1800 Vomiting,

Diarrhoea

Example 1 1.67 0.88 0.79 45.89 Nil Symptomatic

Relief

MC 52/M 12.31 10.94 1 .37 2300 Bodyache,

vomiting, fever

Example 1 1.15 0.69 0.46 35.56 - - Nil Relief

SC 24/M 13.12 10.98 2.14 2000 Vomiting

Diarrhorea,

Fever

Example 1 1.22 0.67 0.55 39.9 Nil Symptomatic

Relief

LB 50/M 8.56 7.12 1 .44 1600 Vomiting,

bodyache

1.56 0.89 0.67 50.12 Nil Symptomatic

Relief

VP 8/M 10.23 8.98 1 .25 1900 - - Vomiting, fever

1.34 0.88 0.46 36.16 - - Nil Relief