DESC:FORM 2

THE PATENTS ACT 1970
(SECTION 39 OF 1970)

&

THE PATENT RULES, 2003

COMPLETE SPECIFICATION
(Section 10 and Rule 13)

NOVEL LIVER HEALTH COMPOSITION AND PROCESS FOR PREPARATION THEREOF

We, STABICON LIFE SCIENCES PVT LTD
having address at No. 22, 7th cross, Jaibharath Nagar, Bangolore-560033,
Karnataka, India

The following specification particularly describes the invention and the manner in which it is to be performed:
FIELD OF INVENTION
The present invention relates to a composition comprising Curcuma Nanodrop, Silymarin and N-acetyl L-cysteine.

The present invention relates to a composition comprising Curcuma Nanodrop, Silymarin and N-acetyl L-cysteine for liver health.

The present invention specifically relates to composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine and pharmaceutically acceptable excipients.

The present invention more specifically relates to a composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine and pharmaceutically acceptable excipients selected from fillers, superdisintegrants, binders, glidants, lubricants, adsorbent carrier, flavors and solvents.

The present invention also relates to a process for the preparation of comprising Curcuma Nanodrop, Silymarin and N-acetyl L-cysteine.

BACKGROUND OF INVENTION
The liver is a critical organ in the human body that is responsible for an array of functions that help support metabolism, immunity, digestion, detoxification, vitamin storage among other functions. It interacts with the endocrine and gastrointestinal systems by aiding in digestion and metabolism. It plays a role in hematology with clotting factor and protein synthesis, heme breakdown into unconjugated bilirubin and conjugates it, sex hormone metabolism and produces carrier proteins that are important in reproduction and development, thyroid hormone function as the site of deiodination of T4 to T3. Finally, Kupffer cells and Pit cells play an important role in the body’s immunologic system.

The major functions of liver is Bile Production, Fat-Soluble Vitamin Storage and/or Metabolism, Drug Metabolism, Bilirubin Metabolism and many Other Functions. Cirrhosis is a result of continuous liver injury, inflammation, fibrosis, and necrosis. Alcoholism and chronic hepatitis B and C commonly cause cirrhosis. Hepatitis C is the most damaging. The fibrosis present in cirrhosis occurs from the secretion of TGF-beta from the Ito cells in the space of Disse.

Curcumin (diferuloylmethane) is the main curcuminoid present in turmeric and responsible for its yellow color. Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. Curcumin has also been shown to have significant wound healing properties. Curcumin is a natural polyphenolic substance that has been used since ancient times in Ayurveda for its healing properties, as it reduces inflammation and acts on several healing stages.

Curcumin is a bright yellow chemical produced by Curcuma longa plants. It is the principal curcuminoid of turmeric (Curcuma longa), a member of the ginger family, Zingiberaceae. Curcumin, chemically described as (1E, 6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadien-3,5-dione. It is a yellowish crystalline, odorless powder, poorly soluble in water, petroleum ether, and benzene, soluble in ethyl alcohols, glacial acetic acid, and in propylene glycol, very soluble in acetone and ethyl ether.

Curcuminoids are phenolic compounds extracted from the dried rhizomes of Curcuma longa (Turmeric) having potent anti-inflammatory and anti-oxidant properties. Curcuminoid and a non-curcuminoid in this formulation is manufactured as curcuma nano drops separately by mixing non-ionic solubilizer and emulsifier and a Curcumin removed turmeric oleoresin under heating.

Curcumin

Demethoxycurcumin

Bisdemethoxycurcumin

Non-curcuminoids are basically all other biologically active compounds of turmeric excluding curcuminoids. The immunomodulatory and chemo-preventive activity of a-turmerone, a non-curcuminoid, was revealed with regards to its potency to be equivalent to curcuminoids (Yue GGL et al, 2010). AR-turmerone, a non-curcuminoid, has shown to possess potent anti-inflammatory, anti-oxidative and anti-platelet properties (S Toden et al, 2017).

The non-Curcuminoid fraction of turmeric has an inhibitory effect on fat accumulation in the liver by promoting lipid metabolism in NASH model rats (Watanabe et al. Sci Rep 13, 20742 (2023))

Non-curcuminoids are isolated from the mother liquor after isolation of Curcumin from oleoresin is known as curcumin removed turmeric oleoresin(CRTO) and it has shown antimicrobial properties (Jayaprakasha et al,2001).

Silymarin is a flavonolignans extracted from the milk thistle Silybum marianum (L.) gaernt. Silymarin has been shown to possess various pharmacological properties like hepatoprotective, antioxidant, antiinflammatory, anticancer, and cardioprotective activities. The chemical name of Silymarin is (2R,3R)-2-[(2R,3R)-2,3-Dihydro-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-1,4-benzodioxin-6-yl]-2,3-dihydro-3,5,7-trihydroxy-4H-1-benzopyran-4-one. Silymarin has a chemical formula of C25H22O10 and a molecular mass of 482.44 g/mol. It has a structural formula of:

Silymarin

N Acetyl L Cysteine also known as Acetylcystein and serves as a prodrug to L-cysteine, a precursor to the biologic antioxidant glutathione. Hence administration of acetylcysteine replenishes glutathione stores. Acetylcysteine is extensively liver metabolized, CYP450 minimal, urine excretion is 22–30% with a half-life of 5.6 hours in adults and 11 hours in newborns. The chemical name of Acetylcystein is N-Acetyl-L-cysteine. Acetylcystein has a chemical formula of C5H9NO3S and a molecular mass of 163.19 g/mol. It has a structural formula of:

Acetylcystein
EP 2 070 545 A1 discloses oral compositions containing :a) mint essential oil; b) Curcuma longa derivatives; c) Olea europea derivatives; and possibly one or more of: d) N-acetylcysteine; e) glutathione; f) ubidecarenone; g) lactoferrin; h) carotenoids; i) polyphenols; j) vitamin C; k) vitamin E; l) St. John's Wort extract or a derivative thereof; m) kava kava extract or a derivative thereof; n) valerian extract or a derivative thereof; o) saffron extract or a derivative thereof; p) camomile extract or a derivative thereof; q) passionflower extract or a derivative thereof; r) griffonia extract or a derivative thereof; wherein derivatives extracted from Curcuma longa are present in the form of a dried extract or as curcumin.

US 7,241,461 B2 (US 2005/0226942 A1) discloses a composition comprising: (a) at least about 150 milligrams Bacopa monniera extract, wherein said Bacopa monniera extract is comprised of 45 percent bacosides; at least about 225 milligrams silybum marianum (milk thistle) extract, wherein said milk thistle extract is comprised of between about 70 percent and about 80 percent silymarin; at least about 150 mg Withania somnifera (ashwagandha) powder; at least about 75 milligrams Camellia sinensis (green tea extract); wherein said green tea extract is comprised of 98 percent polyphenols; said polyphenols comprised of 45 percent (-)-epigallocatechin gallate; at least about 75 milligrams Curcuma longa (turmeric) extract.

US 9,603,830 B2 (US 2015/0342923 A1) discloses a tablet or capsule for mitigating the adverse effects of alcohol consumption in a human in need thereof consisting essentially of therapeutically effective amounts of prickly pear extract, silymarin, ginger root extract, dihydromyricetin and N-acetyl cysteine.

None of the prior-art document discloses teaches a tablet composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine of present application.

The inventors of the present application have developed a novel composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine for liver heath and helps in the management of Fatty Liver, Alcoholic Fatty Liver, NAFLD & NASH. The present invention also relates to process for the preparation of composition comprising Curcuma Nanodrop, Silymarin and N-acetyl L-cysteine.

OBJECTIVE OF INVENTION
The main objective of the present invention is to provide a composition comprising Curcuma Nanodrop, Silymarin and N-acetyl L-cysteine.

Another objective of the present invention is to provide a composition comprising Curcuma Nanodrop, Silymarin and N-acetyl L-cysteine for liver health.

Another objective of the present invention is to provide a composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine and pharmaceutically acceptable excipients.

Another objective of the present invention is to provide a composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine and pharmaceutically acceptable excipients selected from fillers, superdisintegrants, antioxidants, binders, glidants, lubricants, adsorbent carrier, flavors and solvents.

Another objective of the present invention is to provide a process for the preparation of composition comprising Curcuma Nanodrop, Silymarin and N-acetyl L-cysteine.

SUMMARY OF INVENTION
Accordingly, the present invention provides provide a composition comprising Curcuma Nanodrop, Silymarin and N-acetyl L-cysteine.

One embodiment of the present invention provides a composition comprising Curcuma Nanodrop, Silymarin and N-acetyl L-cysteine for liver health.

One embodiment of the present invention provides a composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine and pharmaceutically acceptable excipients.

Another embodiment of the present invention provides a composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine and pharmaceutically acceptable excipients, wherein said tablet coated with film coating.

Another embodiment of the present invention provides a composition comprising Curcuma (Curcuma longa) Nanodrop, Silymarin, N-acetyl L-cysteine and one or more other components, wherein other components are selected from Dandelion Root (Taraxacum officinale) extract, Bhumyamalaki (Phyllanthus amarus) extract, Kutki (Picrorhiza kurroa) extract, Prickly Pear (Opuntia ficus-indica) extract, Licorice (Glycyrrhiza glabra) extract, Chicory root (Cichorium endivia) extract, Bhringraj (Eclipta alba) extract, Artichoke extract, Glutathione reduced, Barberry (Root Bark) (Berberis vulgaris), Alpha lipoic acid , Selenium (as SelenoExcell® selenium yeast) L-leucine, Trimethylglycine (as betaine anhydrous), Choline (as bitartrate), Inositol and Taurine.

Another embodiment of the present invention provides a composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine, one or more other natural extracts and pharmaceutically acceptable excipients.

Another embodiment of the present invention provides a composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine, Dandelion root (Taraxacum officinale) extract, Kutki (Picrorhiza kurroa) extract, Bhumyamalaki (Phyllanthus amarus) extract and pharmaceutically acceptable excipients selected from fillers, superdisintegrants, binders, glidants, lubricants, adsorbent carrier, flavors and solvents.
Yet another embodiment of the present invention provides a tablet composition comprising:
a) 0.1% to 3% (w/w) of Curcuma Nanodrop,
b) 5% to 30% (w/w) of Silymarin,
c) 5% to 50% (w/w) of N-acetyl L-cysteine,
d) 5% to 60% (w/w) of fillers,
e) 1% to 10% (w/w) of binders,
f) 0.1% to 5% (w/w) of glidants, and
g) 0.1% to 5% (w/w) of lubricants.

Yet another embodiment of the present invention provides a tablet composition comprising:
a) 0.1% to 3% (w/w) of Curcuma Nanodrop,
b) 5% to 30% (w/w) of Silymarin,
c) 5% to 50% (w/w) of N-acetyl L-cysteine,
d) 0.1% to 70% of other extracts or components,
e) 5% to 60% (w/w) of fillers,
f) 1% to 10% (w/w) of binders,
g) 0.1% to 5% (w/w) of glidants, and
h) 0.1% to 5% (w/w) of lubricants.

Yet another embodiment of the present invention provides a tablet composition comprising:
a) 0.1% to 3% (w/w) of Curcuma Nanodrop,
b) 5% to 30% (w/w) of Silymarin,
c) 5% to 50% (w/w) of N-acetyl L-cysteine,
d) 0.1% to 10% of Dandelion root extract,
e) 0.1% to 10% of Kutki extract,
f) 0.1% to 10% of Bhumyamalaki extract,
g) 5% to 60% (w/w) of fillers,
h) 1% to 10% (w/w) of binders,
i) 0.1% to 5% (w/w) of glidants, and
j) 0.1% to 5% (w/w) of lubricants.

Yet another embodiment of the present invention provides a tablet composition comprising:
a) 0.1% to 3% (w/w) of Curcuma Nanodrop,
b) 5% to 30% (w/w) of Silymarin,
c) 5% to 50% (w/w) of N-acetyl L-cysteine,
d) 5 % to 40% (w/w) of microcrystalline cellulose,
e) 1% to 10% (w/w) of povidone,
f) 0.1% to 5% (w/w) of colloidal silicon dioxide, and
g) 0.1% to 5% (w/w) of magnesium stearate.

Yet another embodiment of the present invention is to provide a process for the preparation of composition comprising Curcuma Nanodrop, Silymarin and N-acetyl L-cysteine.

Yet another embodiment of the present invention is to provide a process for the preparation of composition comprising Curcuma Nanodrop, Silymarin and N-acetyl L-cysteine, wherein the process involves wet granulation method.

In yet another embodiment, the present invention provides process for preparing tablet, wherein the process comprising steps of:
a) sifting and mixing Silymarin, N-acetyl L-cysteine, fillers and glidant,
b) adsorbing Curcuma Nanodrop with impeller,
c) dissolving the binder in solvent to prepare binder solution,
d) granulating the mixture using high shear mixer granulator,
e) drying and sizing the granules and adding extragranular materials,
f) lubricating and compressing the blend, and
g) coating the tablet with film coating material and packing.

In yet another embodiment, the present invention provides process for preparing tablet, wherein the process comprising steps of:
a) sifting and mixing Silymarin, N-acetyl L-cysteine, dibasic calcium phosphate, microcrystalline cellulose and colloidal silicon dioxide,
b) dry mixing the materials in high shear mixer granulator (HSMG),
c) adsorbing Curcuma Nanodrop with impeller,
d) dissolving the povidone in isopropyl alcohol to prepare binder solution,
e) granulating the mixture using high shear mixer granulator,
f) drying and sizing the granules and adding microcrystalline cellulose, colloidal silicon dioxide, crospovidone and magnesium stearate,
g) blending the granules and lubricating with magnesium stearate,
h) compressing the blend, and
i) coating the tablet with film coating material instamoist shield yellow and packing.

In yet another embodiment, the present invention provides process for preparing curcuma Nanodrop, wherein process comprising steps of:
a) mixing non-ionic solubilizer and emulsifier and a Curcumin removed turmeric oleoresin under heating,
b) adding Curcumin to the mixture under stirring to form a uniform solution,
c) Cooling the solution and adding Ethanol,
d) Sonicating the final solution to obtain a uniformly interspersed particle formulation of curcuma nano drops solution comprising an ultrafine and a fine particle comprising a curcuminoid and a non-curcuminoid.

DETAILED DESCRIPTION OF THE INVENTION
The term "comprising", which is synonymous with "including", "containing", or "characterized by" here is defined as being inclusive or open-ended, and does not exclude additional, unrecited elements or method steps, unless the context clearly requires otherwise.

The present invention provides a composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine and pharmaceutically acceptable excipients selected from fillers, superdisintegrants, binders, glidants, lubricants, adsorbent carrier, flavors and solvents.

Another embodiment of the present invention provides a composition comprising Curcuma (Curcuma longa) Nanodrop, Silymarin, N-acetyl L-cysteine and one or more other components, wherein other components selected from Dandelion Root (Taraxacum officinale) extract, Bhumyamalaki (Phyllanthus amarus) extract, Kutki (Picrorhiza kurroa) extract, Prickly Pear (Opuntia ficus-indica) extract, Licorice (Glycyrrhiza glabra) extract, Chicory root (Cichorium endivia) extract, Bhringraj (Eclipta alba) extract, Artichoke extract, Glutathione reduced, Barberry (Root Bark) (Berberis vulgaris), Alpha lipoic acid , Selenium (as SelenoExcell® selenium yeast) L-leucine, Trimethylglycine (as betaine anhydrous), Choline (as bitartrate), Inositol and Taurine.

The concentration of Curcuma Nano drop used in the composition is from 0.1% to 3% of the total weight of the composition.

The concentration of Silymarin used in the composition is from 5% to 30% (w/w) of the total weight of the composition.

The concentration of N-acetyl L-cysteine used in the composition is from 5% to 50% (w/w) of the total weight of the composition.

The concentration of other extracts or components used in the composition is from 0.1% to 70% (w/w) of the total weight of the composition,

Fillers used in the present invention are selected from and not limited to mannitol, microcrystalline cellulose, MCC PH 101, MCC PH 102, powdered cellulose, dibasic calcium phosphate, lactose (anhydrous or monohydrate), compressible sugar, fructose, dextranes, sorbitol, lactitol, saccharose, siliconised microcrystalline cellulose, calcium hydrogen phosphate, dibasic calcium hydrogen phosphate, calcium carbonate, calcium lactate or mixtures thereof.

The concentration of fillers used in the composition is from 5% to 60% (w/w) of the total weight of the composition.

Superdisintegrants used in the present invention are selected from and not limited to crospovidone XL, carboxymethylcellulose calcium(CMC-Ca), carboxymethylcellulose sodium (CMC-Na), crosslinked sodium carboxymethyl cellulose as e.g. Ac-Di-Sol®, Primellose®, Pharmacelt® XL, Explocel®, and Nymcel® ZSX having a molecular weight of 90000-700000, sodium starch glycolate e.g. Explosol®, Explotab®, Glycolys®, Primojel®, Tablo®, Vivastar® P, in particular having molecular weight is 500000-11000000, crosslinked polyvinylpolypyrrolidone (Plasone-XL®, Polyplasdone® XL and Kollidon® CL) in particular having a molecular weight in excess of 1000000, more particularly having a particle size distribution of less than 400 microns or less than 74 microns, microcrystalline cellulose, L-HPC (low-substituted hydroxypropylcellulose), sodium carboxymethyl starch, sodium glycolate of potato starch, partially hydrolysed starch, wheat starch, maize starch, rice starch or potato starch, corn starch, pregelatinized starch or mixtures thereof.

The concentration of superdisintegrants used in the composition is from 1% to 10% (w/w) of the total weight of the composition.

Binders used in the present invention are selected from and not limited to sucrose and gelatin, polyvinylpyrrolidone (Povidone), polysaccharide acid, magnesium aluminum silicate, cellulose material, glucose, starch, polyethylene glycol, methylcellulose, sodium carboxymethylcellulose, sodium alginate, agar, alginic acid and alginates, carrageenan calcium, polyethylene glycol, guar gum, bentonite, polymethacrylate, Methylcellulose, hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (Klucel®), ethylcellulose (Ethocel), pregelatinized starch, microcrystalline cellulose or mixtures thereof.

The concentration of binders used in the composition is from 1% to 10% (w/w) of the total weight of the composition.

Glidants used in the present invention are selected from and not limited to as talc, fumed silica, magnesium stearate, stearic acid, colloidal silicon dioxide, silicon dioxide, magnesium trisilicate or mixtures thereof.

The concentration of glidants used in the composition is from 0.1% to 5% (w/w) of the total weight of the composition.

Lubricants used in the present invention are selected from and not limited to sodium stearyl fumarate, sodium oleate, sodium stearate, sodium chloride, stearic acid, magnesium stearate, corn starch, sodium benzoate, light mineral oil, sodium acetate, calcium stearate, talc, alkyl sulfate, wax, glyceride, glyceryl behenate, sodium acetate, colloidal silica, hydrogenated vegetable oil, polyethylene glycol, sodium benzoate or mixtures thereof.

The concentration of lubricants used in the composition is from 0.1% to 5% (w/w) of the total weight of the composition.

Adsorbent carrier used in the present invention is selected from and not limited to Neusilin, Magnesium aluminosilicates and mixtures thereof. Neusilin® contains oxides, hydroxides, carbonates, or silicates of Na, Ca, Mg, and Al, or their complexes.

The concentration of adsorbent carrier used in the composition is from 0.1% to 5% (w/w) of the total weight of the composition.

Flavouring agents used in the present invention are selected from and not limited to lemon flavour, peppermint flavour, fruit flavor, lemon-lime, orange, sour cherry, flavor of mint, honey lemon, vanilla, citrus oil, grapefruit, menthol, L-menthol, cranberry, vanilla berry, bubble gum, cherry, alpha-citral, beta-citral, decanal, aldehyde C-8, aldehyde C-9, aldehyde C-12, and volatile oils, synthetic flavor oils, flavoring aromatics, oils, liquids, oleoresins or extracts derived from plants, leaves, flowers, fruits, stems and combinations thereof mint oils, cocoa, and citrus oils such as orange, grape, lime, cinnamon oil, oil of wintergreen, peppermint oils, clove oil, bay oil, anise oil, eucalyptus, thyme oil, cedar leave oil, oil of nutmeg, oil of sage, oil of bitter almonds and cassia oil and fruit essences including apple, pear, peach, strawberry, raspberry, plum, pineapple, apricot or other fruit flavors or mixture thereof.

The concentration of flavouring agents used in the composition is from 0.001% to 1% (w/w) of the total weight of the composition.

Solvents used in the present invention are selected from and not limited to purified water, absolute alcohol, isopropanol (Isopropyl alcohol) and propanol.

Optionally, the tablets can be coated with conventional materials used for film coating, i. e. as described in "Pharmaceutical Coating Technology", 1995, edited by Graham Cole. Film coating formulations usually contain the following components: polymer (s), plasticizer (s), colourant (s) /opacifier (s), vehicle (s). In film coating suspension the minor quantities of flavours, surfactants and waxes can be used. The majority of the polymers used in film coating are either cellulose derivatives, such as the cellulose ethers, or acrylic polymers and copolymers. Occasionally encountered are high molecular weight polyethylene glycols, polyvinyl pyrrolidone, polyvinyl alcohol and waxy materials. Typical cellulose ethers are hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and methylcellulose. Acrylic polymers comprise a group of synthetic polymers with diverse functionalities. Some of them can be further modified to enhance swelling and permeability by the incorporation of materials such as water soluble cellulose ethers and starches in order to ensure complete disintegration/ dissolution of the film.

The film coating mainly consists of Instamoist shield yellow, Isopropyl Alcohol and Purified water.

Other additives used in the preparations to the compositions of this invention, the following can be used and there were no limitations: stabilizer, surfactant, plasticizer, reducing agent, buffer agent, sweetening agent, base, adsorbent, corrigent, binder, suspending agent, antioxidant, coating agents, wetting agent, wet modifier, antifoaming agent, refrigerative agent, coloring matter, sugar coating agent, isotonizing agent, softener, emulsifying agent, foaming agent, pH modifier, anti-frothing agents, preservatives and solubilizer.

All the actives and excipients used in the present application are procured from the commercial sources. The details are as given below:

S.No. Active/Auxiliary materials Commercial source Detailed address of source
1. Curcuma Mane Kancor Ingredients Private Limited
or
Plant Lipids Mane Kancor Ingredients Ltd and Kancor Ingredients Ltd), Sy.No.278/1, Kanakkankadavu Road, Angamaly South, Angamaly, Ernakulam District, Kerala-683573, India

Plant lipids (P) Ltd, Kolenchery, Cochin-682311
2. Silymarin Sami sabinsa Sami-Sabinsa Group Limited, 19/1 & 19/2, I Main, II Phase Peenya Industrial Area, Bangalore - 560 058
3. N-acetyl L-cysteine Chemkart India Limited Chemkart India Limited, 403,404, K.L. Accolade , Road 6, Golibar, Santacruz( East), Mumbai, Maharashtra, India-400055
4. Dandelion Root (Taraxacum officinale) extract Konark herbals Konark Herbal & Health Care Pvt. Ltd, Plot No. 481/3-B, near Dabhel Check Post, Atiyawad, Dabhel, NANI, Vapi, Dadra and Nagar Haveli and Daman and Diu 396210.
5. Bhumyamalaki (Phyllanthus amarus) extract Konark herbals Konark Herbal & Health Care Pvt. Ltd, Plot No. 481/3-B, near Dabhel Check Post, Atiyawad, Dabhel, NANI, Vapi, Dadra and Nagar Haveli and Daman and Diu 396210.
6. Kutki (Picrorhiza kurroa) extract Konark herbals Konark Herbal & Health Care Pvt. Ltd, Plot No. 481/3-B, near Dabhel Check Post, Atiyawad, Dabhel, NANI, Vapi, Dadra and Nagar Haveli and Daman and Diu 396210.
7. Prickly Pear (Opuntia ficus-indica) extract Konark herbals Konark Herbal & Health Care Pvt. Ltd, Plot No. 481/3-B, near Dabhel Check Post, Atiyawad, Dabhel, NANI, Vapi, Dadra and Nagar Haveli and Daman and Diu 396210.
8. Licorice (Glycyrrhiza glabra) extract Konark herbals Konark Herbal & Health Care Pvt. Ltd, Plot No. 481/3-B, near Dabhel Check Post, Atiyawad, Dabhel, NANI, Vapi, Dadra and Nagar Haveli and Daman and Diu 396210.
9. Chicory root (Cichorium endivia) extract Konark herbals Konark Herbal & Health Care Pvt. Ltd, Plot No. 481/3-B, near Dabhel Check Post, Atiyawad, Dabhel, NANI, Vapi, Dadra and Nagar Haveli and Daman and Diu 396210.
10. Bhringraj (Eclipta alba) extract Konark herbals Konark Herbal & Health Care Pvt. Ltd, Plot No. 481/3-B, near Dabhel Check Post, Atiyawad, Dabhel, NANI, Vapi, Dadra and Nagar Haveli and Daman and Diu 396210.
11. Artichoke extract Konark herbals Konark Herbal & Health Care Pvt. Ltd, Plot No. 481/3-B, near Dabhel Check Post, Atiyawad, Dabhel, NANI, Vapi, Dadra and Nagar Haveli and Daman and Diu 396210.
12. Glutathione reduced Prado chemicals Prado Chemicals, B-32, Trimurti Park, Mamlatdar Wadi Cross, Lane No.6, Malad(West) Mumbai-400064
13. Barberry (Root Bark) (Berberis vulgaris Konark herbals Konark Herbal & Health Care Pvt. Ltd, Plot No. 481/3-B, near Dabhel Check Post, Atiyawad, Dabhel, NANI, Vapi, Dadra and Nagar Haveli and Daman and Diu 396210.
14. Alpha lipoic acid Meteoric biopharma Meteoric Biopharmaceuticals, 9th Floor, Earth Arise Building, Near YMCA Club, S.G. Highway, Ahmedabad-380015, Gujarat.
15. Selenium (as SelenoExcell® selenium yeast) L-leucine Meteoric biopharma Meteoric Biopharmaceuticals, 9th Floor, Earth Arise Building, Near YMCA Club, S.G. Highway, Ahmedabad-380015, Gujarat.
16. Trimethylglycine (as betaine anhydrous) Chemkart India Limited Chemkart India Limited, 403,404, K.L. Accolade , Road 6, Golibar, Santacruz( East), Mumbai, Maharashtra, India-400055
17. Choline (as bitartrate) Prado chemicals Prado Chemicals, B-32, Trimurti Park, Mamlatdar Wadi Cross, Lane No.6, Malad(West) Mumbai-400064
18. Inositol Meteoric biopharma Meteoric Biopharmaceuticals, 9th Floor, Earth Arise Building, Near YMCA Club, S.G. Highway, Ahmedabad-380015, Gujarat.
19. Taurine Prado chemicals Prado Chemicals, B-32, Trimurti Park, Mamlatdar Wadi Cross, Lane No.6, Malad(West) Mumbai-400064
The present invention is illustrated in detail but not limiting to, the following examples. It will be apparent to those skilled in the art that many modifications, both to materials and methods, may be practiced without departing from the scope of the invention.

Example 1
S.No. Ingredient name mg/tab % wt by Formula
Dry Mix
1. Curcuma Nanodrop 5.00 0.455
2. Silymarin (Milk Thistle Extract (Silybum marianum)) 140.00 12.727
3. N-Acetyl L-Cysteine 400. 36.583
4. Dibasic calcium phosphate anhydrous Powder (DCP) 100.00 9.091
5. Microcrystalline cellulose PH 101 266.09 24.190
6. Silicon dioxide 5.00 0.455
Binder solution
7. Povidone K 30 16.50 1.500
8. Isopropyl alcohol qs qs
Extragranular portion
9. MCC PH 102 110.00 10.00
10. Silicon dioxide 5.00 0.455
11. Crospovidone XL 40.00 3.636
12. Magnesium Stearate 10.00 0.909
13. Lemon flavour Natural
21070920 0.25 -
14. Peppermint flavour natural 21070918 0.08 -
Film coating
15. Instamoist shield yellow 32.67
16. Isopropyl Alcohol 133.5
17. Purified water 133.5

Manufacturing process
1. Sift all the intragranular materials through 30 mesh sieve,
2. Add Milk Thistle extract, N-Acetyl-L-Cysteine, Dibasic calcium phosphate anhydrous, Microcrystalline cellulose PH 101 and Silicon dioxide in a suitable High shear mixer granulator and mix with impeller at slow speed for 10 minutes,
3. Adsorb curcuma nanodrop on step 2 materials in High shear mixer granulator and mix with impeller at slow speed for 3 minutes,
4. Disperse Povidone K-30 in Isopropyl alcohol under stirring and continue stirring until lump free dispersion is obtained,
5. Add step 4 binder to step 3 materials in the High shear mixer granulator and mix with impeller at slow speed and chopper off to form granules,
6. Air Dry step 5 granules and further continue drying till LOD of granules is achieved in FBD with heater off,
7. Sift the dried granules through 20 mesh sieve. Mill the 20 mesh retained granules through multimill fitted with 1.5mm screen and resift the milled granules through 20 mesh sieve,
8. Sift Microcrystalline cellulose PH102, silicon dioxide, Crospovidone XL, Lemon flavour, Peppermint flavour through 40 mesh sieve and add to step 7 granules in the octagonal blender and mix for 5 minutes,
9. Sift Magnesium stearate through 40 mesh sieve and add to step 8 materials in the octagonal blender and mix for 3 minutes,
10. Compress lubricated blend of step 9 using suitable punches on a compression machine,
11. Take the required quantity of Purified water and Isopropyl alcohol in a suitable vessel and mix using a stirrer. To this disperse Instamoist shield yellow under stirring and continue further stirring for 45 minutes,
12. Film coat the step 10 compressed tablets using step 11 film coating dispersion to target weight gain.

Dissolution Data for composition of Example 1
Sample No Absorbance
(Silymarin) % dissolved at 45 minutes (Silymarin) Area
(N-Acetyl Cysteine) % dissolved at 45 minutes (N-Acetyl Cysteine)
Sample 1 0.9487 86 838485 85
Sample 2 0.9485 86 836982 85
Sample 3 0.9443 86 829743 85
Sample 4 0.9437 86 836688 85
Sample 5 0.9474 86 822824 84
Sample 6 0.9404 86 819589 84
Mean NA 86 NA 85
% RSD NA 00 NA 0.6

Stability Data for composition of Example 1
Condition Initial 1M_40/75 2M_40/75 3M_30/75 3M_40/75
Average weight 1138mg 1140mg 1141mg 1142mg 1143mg
Assay (%)
N-Acetyl Cysteine 96.4% 98.8% 97.4% 95.5% 98.3%
Silymarin 100.7% 94.7% 98.1% 97.1% 97.5%

Example 2:
S.No. Ingredient Name mg/tab % w/w
1 Curcuma (Curcuma longa) nanodrop 5.00 0.42
2 Milk Thistle Extract (Silybum marianum) 140.00 11.67
3 N Acetyl L Cysteine 400.00 33.33
4 Dibasic calcium phosphate anhydrous 100.00 8.33
5 Microcrystalline cellulose PH 101 268.50 22.38
6 Silicon dioxide 5.00 0.42
7 Povidone K-30 16.50 1.37
8 Isopropyl alcohol qs
9 Microcrystalline cellulose PH 102 110.00 9.17
10 Silicon dioxide 5.00 0.42
11 Crospovidone XL 10.00 0.83
12 Magnesium stearate 10.00 0.83
Average Weight(core) 1200.00
Film coating
13 Instamoist shield yellow 36.00
14 Isopropyl Alcohol 182.00
15 Purified water 182.00
Average Weight(coated) 1236.00

Manufacturing process:
1. Sift all the intragranular materials through 30 mesh sieve,
2. Add Milk Thistle extract, N-Acetyl-L-Cysteine, Dibasic calcium phosphate anhydrous, Microcrystalline cellulose PH 101 and Silicon dioxide in a suitable High shear mixer granulator and mix with impeller at slow speed for 10 minutes,
3. Adsorb curcuma nanodrop on step 2 materials in High shear mixer granulator and mix with impeller at slow speed for 3 minutes,
4. Disperse Povidone K-30 in Isopropyl alcohol under stirring and continue stirring until lump free dispersion is obtained,
5. Add step 4 binder to step 3 materials in the High shear mixer granulator and mix with impeller at slow speed and chopper off to form granules,
6. Air Dry step 5 granules and further continue drying till LOD of granules is achieved in FBD with heater off,
7. Sift the dried granules through 20 mesh sieve. Mill the 20 mesh retained granules through multimill fitted with 1.5mm screen and resift the milled granules through 20 mesh sieve,
8. Sift Microcrystalline cellulose PH102, silicon dioxide, Crospovidone XL through 40 mesh sieve and add to step 7 granules in the octagonal blender and mix for 5 minutes,
9. Sift Magnesium stearate through 40 mesh sieve and add to step 8 materials in the octagonal blender and mix for 3 minutes,
10. Compress lubricated blend of step 9 using suitable punches on a compression machine,
11. Take the required quantity of Purified water and Isopropyl alcohol in a suitable vessel and mix using a stirrer. To this disperse Instamoist shield yellow under stirring and continue further stirring for 45 minutes,
12. Film coat the step 10 compressed tablets using step 11 film coating dispersion to target weight gain.

Example 3:
S.No. Ingredient Name mg/tab % w/w
1 Milk Thistle (Silybum marianum) extract 140.00 11.67
2 Dandelion Root (Taraxacum officinale) extract 50.00 4.17
3 Curcuma (Curcuma longa) nanodrop 5.00 0.42
4 N-Acetyl-L-Cysteine 400.00 33.33
5 Sorbitol 350 29.17
6 Povidone K-30 40.00 3.33
7 Isopropyl Alcohol qs qs
8 Microcrystalline cellulose PH 102 200 16.67
9 Silicon dioxide 5.00 0.42
10 Magnesium Stearate 10.00 0.83
Average Weight(core) 1200.00
Film coating
11 Instamoist shield yellow 36.00
12 Isopropyl Alcohol 182.00
13 Purified water 182.00
Average Weight(coated) 1236.00

Manufacturing process:
1. Sift all the intragranular materials through 30 mesh sieve,
2. Adsorb curcuma on Sorbitol and air dry for 60 minutes. Resift the adsorbed granules through 20 mesh sieve,
3. Add Milk Thistle extract, Dandelion root extract, N-Acetyl-L-Cysteine and step 2 adsorbed curcuma in a suitable High shear mixer granulator and mix with impeller at slow speed for 10 minutes,
4. Disperse Povidone K-30 in Isopropyl alcohol under stirring and continue stirring until lump free dispersion is obtained,
5. Add step 4 binder to step 3 materials in the High shear mixer granulator and mix with impeller at slow speed and chopper off to form granules,
6. Air Dry step 5 granules and further continue drying till LOD of granules is achieved in FBD with heater off,
7. Sift the dried granules through 20 mesh sieve. Mill the 20 mesh retained granules through multimill fitted with 1.5mm screen and resift the milled granules through 20 mesh sieve,
8. Sift Microcrystalline cellulose PH102, silicon dioxide through 40 mesh sieve and add to step 7 granules in the octagonal blender and mix for 5 minutes,
9. Sift Magnesium stearate through 40 mesh sieve and add to step 8 materials in the octagonal blender and mix for 3 minutes,
10. Compress lubricated blend of step 9 using suitable punches on a compression machine,
11. Take the required quantity of Purified water and Isopropyl alcohol in a suitable vessel and mix using a stirrer. To this disperse Instamoist shield yellow under stirring and continue further stirring for 45 minutes,
12. Film coat the step 10 compressed tablets using step 11 film coating dispersion to target weight gain.

Stability Data for composition of Example 3
Condition Initial 1M_40/75 2M_40/75 3M_30/75 3M_40/75
Assay (%)
N-Acetyl Cysteine 100.7% 100.3% 100.6% 101.8% 101.3%
Silymarin 96.4% 94.0% 99.6% 98.6% 98.5%

Example 4:
S.No. Ingredient Name mg/tab % w/w
1 Milk Thistle (Silybum marianum) extract 140.00 14.00
2 Bhumyamalaki (Phyllanthus amarus) extract 50.00 5.00
3 Curcuma (Curcuma longa) nanodrop 5.00 0.50
4 N-Acetyl-L-Cysteine 200.00 20.00
5 Kutki (Picrorhiza kurroa) extract 50.00 5.00
6 Sorbitol 350.00 35.00
7 Povidone K-30 40.00 4.00
8 Isopropyl Alcohol qs
9 Microcrystalline cellulose PH 102 150.00 15.00
10 Silicon dioxide 5.00 0.50
11 Magnesium Stearate 10.00 1.00
Average Weight(core) 1000.00
Film coating
12 Instamoist shield yellow 30.00
13 Isopropyl Alcohol 151.00
14 Purified water 151.00
Average weight(coated) 1030.00

Manufacturing process:
1. Sift all the intragranular materials through 30 mesh sieve,
2. Adsorb curcuma on Sorbitol and air dry for 60 minutes. Resift the adsorbed granules through 20 mesh sieve,
3. Add Milk Thistle extract, Bhumyamalaki extract, N-Acetyl-L-Cysteine, Kutki extract and step 2 adsorbed curcuma in a suitable High shear mixer granulator and mix with impeller at slow speed for 10 minutes,
4. Disperse Povidone K-30 in Isopropyl alcohol under stirring and continue stirring until lump free dispersion is obtained,
5. Add step 4 binder to step 3 materials in the High shear mixer granulator and mix with impeller at slow speed and chopper off to form granules,
6. Air Dry step 5 granules and further continue drying till LOD of granules is achieved in FBD with heater off,
7. Sift the dried granules through 20 mesh sieve. Mill the 20 mesh retained granules through multimill fitted with 1.5mm screen and resift the milled granules through 20 mesh sieve,
8. Sift Microcrystalline cellulose PH102, silicon dioxide through 40 mesh sieve and add to step 7 granules in the octagonal blender and mix for 5 minutes,
9. Sift Magnesium stearate through 40 mesh sieve and add to step 8 materials in the octagonal blender and mix for 3 minutes,
10. Compress lubricated blend of step 9 using suitable punches on a compression machine,
11. Take the required quantity of Purified water and Isopropyl alcohol in a suitable vessel and mix using a stirrer. To this disperse Instamoist shield yellow under stirring and continue further stirring for 45 minutes,
12. Film coat the step 10 compressed tablets using step 11 film coating dispersion to target weight gain.

Stability Data for composition of Example 4
Condition Initial 1M_40/75 2M_40/75 3M_30/75 3M_40/75
Average weight 1033 mg 1033mg 1033mg 1034mg 1035mg
Assay (%)
N-Acetyl Cysteine 101.2% 101.7% 99.8% 103.6% 99.8%
Silymarin 99.1% 99.1% 98.4% 98.9 97.9

Example 5:
S.No. Ingredient Name mg/tab % w/w
1 Milk Thistle (Silybum marianum) extract 140.00 14.00
2 Bhumyamalaki (Phyllanthus amarus) extract 50.00 5.00
3 Curcuma (Curcuma longa) nanodrop 5.00 0.50
4 N-Acetyl-L-Cysteine 200.00 20.00
5 Kutki (Picrorhiza kurroa) extract 50.00 5.00
6 Prickly Pear (Opuntia ficus-indica) extract 50.00 5.00
7 Sorbitol 350.00 35.00
8 Povidone K-30 40.00 4.00
9 Isopropyl Alcohol qs
10 Microcrystalline cellulose PH 102 100.00 10.00
11 Silicon dioxide 5.00 0.50
12 Magnesium Stearate 10.00 1.00
Average Weight(core) 1000.00
Film coating
13 Instamoist shield yellow 30.00
14 Isopropyl Alcohol 151.00
15 Purified water 151.00
Average weight(coated) 1030.00

Manufacturing process:
1. Sift all the intragranular materials through 30 mesh sieve,
2. Adsorb curcuma on Sorbitol and air dry for 60 minutes. Resift the adsorbed granules through 20 mesh sieve,
3. Add Milk Thistle extract, Bhumyamalaki extract, N-Acetyl-L-Cysteine, Kutki extract, Prickly pear extract and step 2 adsorbed curcuma in a suitable High shear mixer granulator and mix with impeller at slow speed for 10 minutes,
4. Disperse Povidone K-30 in Isopropyl alcohol under stirring and continue stirring until lump free dispersion is obtained,
5. Add step 4 binder to step 3 materials in the High shear mixer granulator and mix with impeller at slow speed and chopper off to form granules,
6. Air Dry step 5 granules and further continue drying till LOD of granules is achieved in FBD with heater off,
7. Sift the dried granules through 20 mesh sieve. Mill the 20 mesh retained granules through multimill fitted with 1.5mm screen and resift the milled granules through 20 mesh sieve,
8. Sift Microcrystalline cellulose PH102, silicon dioxide through 40 mesh sieve and add to step 7 granules in the octagonal blender and mix for 5 minutes,
9. Sift Magnesium stearate through 40 mesh sieve and add to step 8 materials in the octagonal blender and mix for 3 minutes,
10. Compress lubricated blend of step 9 using suitable punches on a compression machine,
11. Take the required quantity of Purified water and Isopropyl alcohol in a suitable vessel and mix using a stirrer. To this disperse Instamoist shield yellow under stirring and continue further stirring for 45 minutes,
12. Film coat the step 10 compressed tablets using step 11 film coating dispersion to target weight gain.

Stability Data for composition of Example 5
Condition Initial 1M_40/75 2M_40/75 3M_40/75 3M_30/75
Average weight 1030mg 1029mg 1030mg 1031mg 1031mg
Assay (%)
N-Acetyl Cysteine 103.0% 99.6% 99.7% 97.6% 94.6%
Silymarin 95.9% 99.2% 97.6% 101.0% 99.9%

Example 6:
S.No. Ingredient Name mg/tab % w/w
1 Milk Thistle (Silybum marianum) extract 140.00 11.67
2 Bhumyamalaki (Phyllanthus amarus) extract 50.00 4.17
3 Curcuma (Curcuma longa) nanodrop 5.00 0.42
4 N-Acetyl-L-Cysteine 200.00 16.67
5 Kutki (Picrorhiza kurroa) extract 50.00 5.00
6 Prickly Pear (Opuntia ficus-indica) extract 50.00 5.00
7 Licorice (Glycyrrhiza glabra) extract 50.00 5.00
8 Sorbitol 350.00 29.17
9 Povidone K-30 40.00 3.33
10 Isopropyl Alcohol qs
11 Microcrystalline cellulose PH 102 250.00 20.83
12 Silicon dioxide 5.00 0.42
13 Magnesium Stearate 10.00 0.83
Average Weight(core) 1200.00
Film coating
14 Instamoist shield yellow 36.00
15 Isopropyl Alcohol 182.00
16 Purified water 182.00
Average Weight(coated) 1236.00

Manufacturing process:
1. Sift all the intragranular materials through 30 mesh sieve,
2. Adsorb curcuma on Sorbitol and air dry for 60 minutes. Resift the adsorbed granules through 20 mesh sieve,
3. Add Milk Thistle extract, Bhumyamalaki extract, N-Acetyl-L-Cysteine, Kutki extract, Prickly pear extract, Licorice extract and step 2 adsorbed curcuma in a suitable High shear mixer granulator and mix with impeller at slow speed for 10 minutes,
4. Disperse Povidone K-30 in Isopropyl alcohol under stirring and continue stirring until lump free dispersion is obtained,
5. Add step 4 binder to step 3 materials in the High shear mixer granulator and mix with impeller at slow speed and chopper off to form granules,
6. Air Dry step 5 granules and further continue drying till LOD of granules is achieved in FBD with heater off,
7. Sift the dried granules through 20 mesh sieve. Mill the 20 mesh retained granules through multimill fitted with 1.5mm screen and resift the milled granules through 20 mesh sieve,
8. Sift Microcrystalline cellulose PH102, silicon dioxide through 40 mesh sieve and add to step 7 granules in the octagonal blender and mix for 5 minutes,
9. Sift Magnesium stearate through 40 mesh sieve and add to step 8 materials in the octagonal blender and mix for 3 minutes,
10. Compress lubricated blend of step 9 using suitable punches on a compression machine,
11. Take the required quantity of Purified water and Isopropyl alcohol in a suitable vessel and mix using a stirrer. To this disperse Instamoist shield yellow under stirring and continue further stirring for 45 minutes,
12. Film coat the step 10 compressed tablets using step 11 film coating dispersion to target weight gain.

Stability Data for composition of Example 6
Condition Initial 1M_40/75 2M_40/75 3M_40/75 3M_30/75
Average weight 1238mg 1245mg 1254mg 1263mg 1261mg
Assay (%)
N-Acetyl Cysteine 103.7% 100.5% 100.0% 99.9% 100.4%
Silymarin 97.8% 97.5% 94.7% 100.8% 101.5%

Example 7:
S.No. Ingredient Name mg/tab % w/w
1 Milk Thistle (Silybum marianum) extract 100.00 8.33
2 Bhumyamalaki (Phyllanthus amarus) extract 50.00 4.17
3 Curcuma (Curcuma longa) nanodrop 5.00 0.42
4 N-Acetyl-L-Cysteine 200.00 16.67
5 Kutki (Picrorhiza kurroa) extract 50.00 5.00
6 Prickly Pear (Opuntia ficus-indica) extract 50.00 5.00
7 Licorice (Glycyrrhiza glabra) extract 50.00 5.00
8 Chicory root (Cichorium endivia) extract 50.00 5.00
9 Sorbitol 350.00 29.17
10 Povidone K-30 40.00 3.33
11 Isopropyl Alcohol qs
12 Microcrystalline cellulose PH 102 240.00 20.00
13 Silicon dioxide 5.00 0.42
14 Magnesium Stearate 10.00 0.83
Average Weight(core) 1200.00
Film coating
15 Instamoist shield yellow 36.00
16 Isopropyl Alcohol 182.00
17 Purified water 182.00
Average Weight(coated) 1236.00

Manufacturing process:
1. Sift all the intragranular materials through 30 mesh sieve,
2. Adsorb curcuma on Sorbitol and air dry for 60 minutes. Resift the adsorbed granules through 20 mesh sieve,
3. Add Milk Thistle extract, Bhumyamalaki extract, N-Acetyl-L-Cysteine, Kutki extract, Prickly pear extract, Licorice extract, Chicory root extract and step 2 adsorbed curcuma in a suitable High shear mixer granulator and mix with impeller at slow speed for 10 minutes,
4. Disperse Povidone K-30 in Isopropyl alcohol under stirring and continue stirring until lump free dispersion is obtained,
5. Add step 4 binder to step 3 materials in the High shear mixer granulator and mix with impeller at slow speed and chopper off to form granules,
6. Air Dry step 5 granules and further continue drying till LOD of granules is achieved in FBD with heater off,
7. Sift the dried granules through 20 mesh sieve. Mill the 20 mesh retained granules through multimill fitted with 1.5mm screen and resift the milled granules through 20 mesh sieve,
8. Sift Microcrystalline cellulose PH102, silicon dioxide through 40 mesh sieve and add to step 7 granules in the octagonal blender and mix for 5 minutes,
9. Sift Magnesium stearate through 40 mesh sieve and add to step 8 materials in the octagonal blender and mix for 3 minutes,
10. Compress lubricated blend of step 9 using suitable punches on a compression machine,
11. Take the required quantity of Purified water and Isopropyl alcohol in a suitable vessel and mix using a stirrer. To this disperse Instamoist shield yellow under stirring and continue further stirring for 45 minutes,
12. Film coat the step 10 compressed tablets using step 11 film coating dispersion to target weight gain.

Stability Data for composition of Example 7
Condition Initial 1M_40/75 2M_40/75 3M_40/75 3M_30/75
Average weight 1240mg 1241mg 1241mg 1242mg 1241mg
Assay (%)
N-Acetyl Cysteine 106.3% 101.1% 99.7% 101.2% 101.6%
Silymarin 96.5% 97.1% 99.1% 97.7% 97.9%

Example 8:
S.No. Ingredient Name mg/tab % w/w
1 Milk Thistle (Silybum marianum) extract 100.00 8.33
2 Bhumyamalaki (Phyllanthus amarus) extract 50.00 4.17
3 Curcuma (Curcuma longa) nanodrop 5.00 0.42
4 N-Acetyl-L-Cysteine 100.00 8.33
5 Kutki (Picrorhiza kurroa) extract 50.00 5.00
6 Prickly Pear (Opuntia ficus-indica) extract 50.00 5.00
7 Licorice (Glycyrrhiza glabra) extract 50.00 5.00
8 Chicory root (Cichorium endivia) extract 50.00 5.00
9 Bhringraj (Eclipta alba) extract 50.00 5.00
10 Sorbitol 350.00 29.17
11 Povidone K-30 40.00 3.33
12 Isopropyl Alcohol qs
13 Microcrystalline cellulose PH 102 290.00 24.17
14 Silicon dioxide 5.00 0.42
15 Magnesium Stearate 10.00 0.83
Average Weight(core) 1200.00
Film coating
16 Instamoist shield yellow 36.00
17 Isopropyl Alcohol 182.00
18 Purified water 182.00
Average Weight(coated) 1236.00

Manufacturing process:
1. Sift all the intragranular materials through 30 mesh sieve,
2. Adsorb curcuma on Sorbitol and air dry for 60 minutes. Resift the adsorbed granules through 20 mesh sieve,
3. Add Milk Thistle extract, Bhumyamalaki extract, N-Acetyl-L-Cysteine, Kutki extract, Prickly pear extract, Licorice extract, Chicory root extract, Bhringraj extract and step 2 adsorbed curcuma in a suitable High shear mixer granulator and mix with impeller at slow speed for 10 minutes,
4. Disperse Povidone K-30 in Isopropyl alcohol under stirring and continue stirring until lump free dispersion is obtained,
5. Add step 4 binder to step 3 materials in the High shear mixer granulator and mix with impeller at slow speed and chopper off to form granules,
6. Air Dry step 5 granules and further continue drying till LOD of granules is achieved in FBD with heater off,
7. Sift the dried granules through 20 mesh sieve. Mill the 20 mesh retained granules through multimill fitted with 1.5mm screen and resift the milled granules through 20 mesh sieve,
8. Sift Microcrystalline cellulose PH102, silicon dioxide through 40 mesh sieve and add to step 7 granules in the octagonal blender and mix for 5 minutes,
9. Sift Magnesium stearate through 40 mesh sieve and add to step 8 materials in the octagonal blender and mix for 3 minutes,
10. Compress lubricated blend of step 9 using suitable punches on a compression machine,
11. Take the required quantity of Purified water and Isopropyl alcohol in a suitable vessel and mix using a stirrer. To this disperse Instamoist shield yellow under stirring and continue further stirring for 45 minutes,
12. Film coat the step 10 compressed tablets using step 11 film coating dispersion to target weight gain.

Example 9:
S.No. Ingredient Name mg/tab % w/w
1 Milk Thistle (Silybum marianum) extract 300.00 21.43
2 Artichoke extract 3.50 0.25
3 Dandelion Root (Taraxacum officinale) extract 50.00 3.57
4 Glutathione reduced 100.00 7.14
5 Curcuma (Curcuma longa) nanodrop 2.50 0.18
6 Licorice Extract (Glycyrrhiza glabra) (root) 100.00 7.14
7 Barberry (Root Bark) (Berberis vulgaris) 30.00 2.14
9 N-Acetyl-L-Cysteine 200.00 14.29
10 Alpha lipoic acid 12.00 0.86
11 Bhumyamalaki (Phyllanthus amarus) extract 50.00 3.57
12 Selenium (as SelenoExcell® selenium yeast) 8.00 0.57
13 L-leucine 40.00 2.86
14 Trimethylglycine (as betaine anhydrous) 50.00 3.57
15 Choline (as bitartrate) 24.33 1.74
16 Inositol 50.00 3.57
17 Taurine 50.00 3.57
18 Sorbitol 150.00 10.71
19 Povidone K-30 25.00 1.78
20 Isopropyl Alcohol qs qs
21 Microcrystalline cellulose PH102 74.67 5.33
23 Silicon dioxide 10.00 0.71
24 Magnesium Stearate 10.00 0.71
Average Weight(core) 1400.00
Film coating
24 Instamoist shield yellow 42.00
25 Isopropyl Alcohol 212.00
26 Purified water 212.00
Average Weight(coated) 1442.00

Manufacturing process:
1. Sift all the intragranular materials through 30 mesh sieve,
2. Adsorb curcuma nanodrop on Sorbitol and air dry for 60 minutes. Resift the adsorbed granules through 20 mesh sieve,
3. Add Milk Thistle extract, Artichoke extract, Bhumyamalaki extract, Dandelion root extract, Glutathione reduced, N-Acetyl-L-Cysteine, Berberry extract, Licorice extract, Alpha lipoic acid and step 2 adsorbed curcuma in a suitable High shear mixer granulator and mix with impeller at slow speed for 10 minutes,
4. Disperse Povidone K-30 in Isopropyl alcohol under stirring and continue stirring until lump free dispersion is obtained,
5. Add step 4 binder to step 3 materials in the High shear mixer granulator and mix with impeller at slow speed and chopper off to form granules,
6. Air Dry step 5 granules and further continue drying till LOD of granules is achieved in FBD with heater off,
7. Sift the dried granules through 20 mesh sieve. Mill the 20 mesh retained granules through multimill fitted with 1.5mm screen and resift the milled granules through 20 mesh sieve,
8. Sift Microcrystalline cellulose PH102, Selenium yeast, L-Leucine, Trimethylglycine, Choline bitartrate, Inositol, Taurine and silicon dioxide through 40 mesh sieve and add to step 7 granules in the octagonal blender and mix for 5 minutes,
9. Sift Magnesium stearate through 40 mesh sieve and add to step 8 materials in the octagonal blender and mix for 3 minutes,
10. Compress lubricated blend of step 9 using suitable punches on a compression machine,
11. Take the required quantity of Purified water and Isopropyl alcohol in a suitable vessel and mix using a stirrer. To this disperse Instamoist shield yellow under stirring and continue further stirring for 45 minutes,
12. Film coat the step 10 compressed tablets using step 11 film coating dispersion to target weight gain.

Example 10:
S.No. Ingredient name mg/tab % formula
Intragranular
1 curcuma Nanodrop 2.50 0.23
2 Milk Thistle (Silybum marianum) extract 70.00 6.36
3 N Acetyl L Cysteine 200.00 18.18
4 Dandelion root extract 50.00 4.55
5 Kutki extract 50.00 4.55
6 Bhumyamalaki extract 50.00 4.55
7 Sorbitol 125.00 11.36
8 Dibasic calcium phosphate 100.00 9.09
9 Silicon di-oxide 5.00 0.45
10 MCC PH 101 266.09 24.19
Binder solution
11 PVP K 30 16.50 1.50
12 Isopropyl alcohol 0.00
Extra granular
13 MCC PH 102 110.00 10.00
14 CrosspovidoneXL 40.00 3.64
15 Silicon Di-oxide 5.00 0.45
16 Magnesium Stearate 10.00 0.91
Film coating
17 Instamoist shield yellow 33
18 Isopropyl Alcohol qs
19 Purified water qs

Manufacturing process
1. Sift all the intragranular materials through 30 mesh sieve,
2. Add Milk Thistle extract, N-Acetyl-L-Cysteine, Dibasic calcium phosphate anhydrous, Microcrystalline cellulose PH 101, Sorbitol and Dandelion root extract, Kutki extract & Bhumyamalaki extract Silicon dioxide in a suitable High shear mixer granulator and mix with impeller at slow speed for 10 minutes,
3. Adsorb curcuma nanodrop on step 2 materials in High shear mixer granulator and mix with impeller at slow speed for 3 minutes,
4. Disperse Povidone K-30 in Isopropyl alcohol under stirring and continue stirring until lump free dispersion is obtained,
5. Add step 4 binder to step 3 materials in the High shear mixer granulator and mix with impeller at slow speed and chopper off to form granules,
6. Air Dry step 5 and further continue drying till LOD of granules is achieved in FBD with heater off,
7. Sift the dried granules through 20 mesh sieve. Mill the 20 mesh retained granules through multimill fitted with 1.5mm screen and resift the milled granules through 20 mesh sieve,
8. Sift Microcrystalline cellulose PH102, silicon dioxide, Crospovidone XL, Lemon flavour, Peppermint flavour through 40 mesh sieve and add to step 7 granules in the octagonal blender and mix for 5 minutes,
9. Sift Magnesium stearate through 40 mesh sieve and add to step 8 materials in the octagonal blender and mix for 3 minutes,
10. Compress lubricated blend of step 9 using suitable punches on a compression machine,
11. Take the required quantity of Purified water and Isopropyl alcohol in a suitable vessel and mix using a stirrer. To this disperse Instamoist shield yellow under stirring and continue further stirring for 45 minutes,
12. Film coat the step 10 compressed tablets using step 11 film coating dispersion to target weight gain.

Example 11:
S.No. Ingredient name mg/tab % formula
Intragranular
1 curcuma Nanodrop 2.50 0.45
2 Milk Thistle (Silybum marianum) extract (Silymarin (80%)) 70.00 12.73
3 N Acetyl L Cysteine 200.00 36.36
4 Dibasic calcium phosphate Anhydrous(DCP) 65.00 11.82
5 Magnesium aluminometasilicate (Neusilin) 5.00 0.91
6 Microcrystalline cellulose 101 104.50 19.00
Binder solution
7 PVP K 30 14.00 2.55
8 Isopropyl alcohol qs qs
9 Purified water qs qs
Extra granular
10 Lemon Natural 3.00 0.55
11 Peppermint 1.00 0.18
12 Microcrystalline cellulose PH 102 55.00 10.00
13 Crospovidone XL 20.00 3.64
14 Purified Talc 5.00 0.91
15 Magnesium Stearate 5.00 0.91
Film coating
16 Insta coat T2F Yellow 17 3.00
17 Dichloromethane (65%) qs
18 Isopropyl alcohol(35%) qs

Manufacturing process
1. Sift all the intragranular materials through 30 mesh sieve,
2. Add Silymarin, N-Acetyl-L-Cysteine, Dibasic calcium phosphate anhydrous, Microcrystalline cellulose PH 101, Neusilin in a suitable High shear mixer granulator and mix with impeller at slow speed for 10 minutes,
3. Adsorb curcuma nanodrop on step 2 materials in High shear mixer granulator and mix with impeller at slow speed for 3 minutes,
4. Disperse Povidone K-30 in Isopropyl alcohol, water under stirring and continue stirring until lump free dispersion is obtained,
5. Add step 4 binder to step 3 materials in the High shear mixer granulator and mix with impeller at slow speed and chopper off to form granules,
6. Air Dry step 5 and further continue drying till LOD of granules is achieved in FBD with heater off,
7. Sift the dried granules through 20 mesh sieve. Mill the 20 mesh retained granules through multimill fitted with 1.5mm screen and resift the milled granules through 20 mesh sieve,
8. Sift Microcrystalline cellulose PH102, Crospovidone XL through #30 mesh, Lemon flavour, Peppermint flavour through 100 mesh sieve and add to step 7 granules in the octagonal blender and mix for 5 minutes,
9. Sift Purified Talc, Magnesium stearate through 60 mesh sieve and add to step 8 materials in the octagonal blender and mix for 3 minutes,
10. Compress lubricated blend of step 9 using suitable punches with target weight on a compression machine,
11. Take the required quantity of dichloromethane and Isopropyl alcohol in a suitable vessel and mix using a stirrer. To this disperse Insta coat T2F Yellow under stirring and continue further stirring for 45 minutes,
12. Film coat the step 10 compressed tablets using step 11 film coating dispersion to target weight gain. ,CLAIMS:WE CLAIM:

1. A composition comprising Curcuma Nanodrop, Silymarin, N-acetyl L-cysteine and pharmaceutically acceptable excipients.

2. The composition as claimed in claim 1, wherein said composition further comprising other components selected from Dandelion Root (Taraxacum officinale) extract, Bhumyamalaki (Phyllanthus amarus) extract, Kutki (Picrorhiza kurroa) extract, Prickly Pear (Opuntia ficus-indica) extract, Licorice (Glycyrrhiza glabra) extract, Chicory root (Cichorium endivia) extract, Bhringraj (Eclipta alba) extract, Artichoke extract, Glutathione reduced, Barberry (Root Bark) (Berberis vulgaris), Alpha lipoic acid , Selenium (as SelenoExcell® selenium yeast) L-leucine, Trimethylglycine (as betaine anhydrous), Choline (as bitartrate), Inositol and Taurine.

3. The composition as claimed in claim 1, wherein said pharmaceutically acceptable excipients selected from fillers, superdisintegrants, binders, glidants, lubricants, adsorbent carrier, flavors and solvents.

4. The composition as claimed in claim 3, wherein said fillers selected from mannitol, microcrystalline cellulose, MCC PH 101, MCC PH 102, powdered cellulose, dibasic calcium phosphate, lactose (anhydrous or monohydrate), compressible sugar, fructose, dextranes, sorbitol, lactitol, saccharose, siliconised microcrystalline cellulose, calcium hydrogen phosphate, Dibasic calcium hydrogen phosphate calcium carbonate, calcium lactate or mixtures thereof, the concentration of fillers is from 5% to 60% (w/w) of the total weight of the composition.

5. The composition as claimed in claim 3, wherein said superdisintegrants selected from crospovidone XL, carboxymethyl cellulose calcium(CMC-Ca), carboxymethylcellulose sodium (CMC-Na), crosslinked sodium carboxymethyl cellulose, sodium starch glycolate, crosslinked polyvinylpolypyrrolidone, microcrystalline cellulose, L-HPC (low-substituted hydroxypropylcellulose), sodium carboxymethyl starch, sodium glycolate of potato starch, partially hydrolysed starch, wheat starch, maize starch, rice starch or potato starch, corn starch, pregelatinized starch or mixtures thereof, concentration of superdisintegrants is from 1% to 10% (w/w) of the total weight of the composition.

6. The composition as claimed in claim 3, wherein said binders are selected from sucrose and gelatin, polyvinylpyrrolidone (Povidone), polysaccharide acid, magnesium aluminum silicate, cellulose material, glucose, starch, polyethylene glycol, methylcellulose, sodium carboxymethylcellulose, sodium alginate, agar, alginic acid and alginates, carrageenan calcium, polyethylene glycol, guar gum, bentonite, polymethacrylate, Methylcellulose, hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (Klucel®), ethylcellulose (Ethocel), pregelatinized starch, microcrystalline cellulose or mixtures thereof, the concentration of binders is from 1% to 10% (w/w) of the total weight of the composition.

7. The composition as claimed in claim 3, wherein said glidants are selected from talc, fumed silica, magnesium stearate, stearic acid, colloidal silicon dioxide, silicon dioxide, magnesium trisilicate or mixtures thereof, the concentration of glidants is from 0.1% to 5% (w/w) of the total weight of the composition.

8. The composition as claimed in claim 3, wherein said lubricants are selected from sodium stearyl fumarate, sodium oleate, sodium stearate, sodium chloride, stearic acid, magnesium stearate, corn starch, sodium benzoate, light mineral oil, sodium acetate, calcium stearate, talc, alkyl sulfate, wax, glyceride, glyceryl behenate, sodium acetate, colloidal silica, hydrogenated vegetable oil, polyethylene glycol, sodium benzoate or mixtures thereof, the concentration of lubricants is from 0.1% to 5% (w/w) of the total weight of the composition.

9. The composition as claimed in claim 3, wherein said adsorbent carrier is selected from and not limited to Neusilin, Magnesium aluminosilicates and mixtures thereof, the concentration of adsorbent carrier used in the composition is from 0.1% to 5% (w/w) of the total weight of the composition.

10. The composition as claimed in claim 3, wherein said flavouring agents are selected from lemon flavour, peppermint flavour, fruit flavor, lemon-lime, orange, sour cherry, flavor of mint, honey lemon, vanilla, citrus oil, grapefruit, menthol, L-menthol, cranberry, vanilla berry, bubble gum, cherry, alpha-citral, beta-citral, decanal, aldehyde C-8, aldehyde C-9, aldehyde C-12, and volatile oils, synthetic flavor oils, flavoring aromatics, oils, liquids, oleoresins or extracts derived from plants, leaves, flowers, fruits, stems and combinations thereof mint oils, cocoa, and citrus oils such as orange, grape, lime, cinnamon oil, oil of wintergreen, peppermint oils, clove oil, bay oil, anise oil, eucalyptus, thyme oil, cedar leave oil, oil of nutmeg, oil of sage, oil of bitter almonds and cassia oil and fruit essences including apple, pear, peach, strawberry, raspberry, plum, pineapple, apricot or other fruit flavors or mixture thereof, the concentration of flavouring agents used in the composition is from 0.001% to 1% (w/w) of the total weight of the composition.

11. The composition as claimed in claim 3, wherein said solvents are selected from purified water, absolute alcohol, isopropanol (Isopropyl alcohol) and propanol.

12. The composition as claimed in claim 1, the tablet composition comprising:
a) 0.1% to 3% (w/w) of Curcuma Nanodrop,
b) 5% to 30% (w/w) of Silymarin,
c) 5% to 50% (w/w) of N-acetyl L-cysteine,
d) 0.1% to 70% of other extracts or components,
e) 5% to 60% (w/w) of fillers,
f) 1% to 10% (w/w) of binders,
g) 0.1% to 5% (w/w) of glidants, and
h) 0.1% to 5% (w/w) of lubricants.

13. The process for the preparation of composition claimed in claim 11, wherein said process comprising steps of:
a) sifting and mixing Silymarin, N-acetyl L-cysteine, fillers and glidant,
b) adsorbing Curcuma Nanodrop with impeller,
c) dissolving the binder in solvent to prepare binder solution,
d) granulating the mixture using high shear mixer granulator,
e) drying and sizing the granules and adding extragranular materials,
f) lubricating and compressing the blend, and
g) coating the tablet with film coating material and packing.

Dated this Twenty Fourth (24th) day of January, 2025

_____________________________
Dr. S. Padmaja
Agent for the Applicant
IN/PA/883