FORM 2THE PATENT ACT 1970(39 of 1970)&The Patents Rules, 2003COMPLETE SPECIFICATION(See section 10 and rule 13)
1. TITLE OF THE INVENTIONA FORMULATION OF ACECLOFENAC TO PROTECT ITS HEPATOTOXIC NATURE
2. APPLICANT (S)(a) NAME: LINCOLN PHARMACEUTICALS LIMITED(b) NATIONALITY: an Indian Company(c) ADDRESS: Nirav complex, Opp Navrang High School,Naranpura, Ahmedabad-380014. Gujarat State, India.
3. PREMABLE TO THE DESCRIPTION
PROVISIONALThe following specification describes the invention. 0 COMPLETEThe following specification particularly describes the invention and the manner in which it is to be performed.
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The present invention relates to a novel formulation of aceclofenac in order to protect against its hepatotoxic nature. More particularly, the present invention relates to a novel formulation of aceclofenac and its dosage forms to protect the liver from hepatotoxic effect of aceclofenac by using amino acid. Background of the Invention:
Aceclofenac is a phenylaceticacid derivative and, it is a inhibitor of prostoglandin synthesis and used in rheumatoid arthiritis. The mode of action of aceclofenac is largely based on the inhibition of prostaglandin synthesis. Aceclofenac is a potent inhibitor of the enzyme cyclooxygenase, which is involved in the production of prostaglandins.
Aceclofenac is well tolerated, with most adverse events being minor and reversible and affecting mainly the GI system.
Till now no efforts has been done to overcome its hepatotoxic effect. Objects of Invention
It is therefore, a principle object of the present invention to provide a formulation of Aceclofenac to prevent its hepatotoxic effect.
Other object of the present invention is to provide simple composition to eliminate hepatotoxic effect of aceclofenac. Summary of the Invention
The present invention provides a pharmaceutical composition comprises of aceclofenac and methionine in a ratio of 1:1 to 2:1 all ratios being in terms of
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weight respectively, and the balance it any comprising one or more conventional additives.
In one embodiment of the invention, the aceclofenac is used as such or in a polymeric form thereof and wherein the methionine is selected from the L isomer, and D isomer or a racemic mixture thereof.
In another embodiment of the invention, the composition is in the form of a tablet, an oral liquid suspension or a capsule.
In another embodiment of the invention, the conventional ingredients are selected from the group consisting of diluents, disintegrants, colorants, flavoring agents, suspending agents and other conventional additives.
In another embodiment of the invention, the oral liquid suspension form comprises aceclofenac in an amount of 100 to 200 mg and methionine in an amount of 50 mg to 100 mg per 5 ml of the dosage.
The present invention also relates to method for the preparation of a pharmaceutical composition comprising of aceclofenac and methionine in a ration of 1:1 to 2:1 all ratios being in terms of weight respectively and the balance if any comprising one or more conventional additives, said method comprising subjecting said aceclofenac to conventional method of tableting, capsule formation or suspension. Detailed Description of Invention:
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Various compounds were studied for their role in preventing hepatotoxic effect of Aceclofenac and a novel composition has been invented for preventing the hepatotoxic effect of Aceclofenac.
1. Formualtion contiains Aceclofenac with Methionine (L isomer, D isomer or racemic mixture {Racemethionine}) as hepatoprotector and hepato-revitalizer.
2. Formulation is developed in the form of tablets, capsules and oral liquid suspension.
3. Quality of Racemethionine in the different formulations ranges from 50 mg to 100 mg.
4. Quality of Aceclofenac in the different formulations ranges from 50 mg to 200 mg.
Various formulations were prepared of aceclofenac along with mehionine in the form of tablets, capsules and oral liquid suspensions by conventional methods. Clinical trials were conducted with the formulations and compared to administration of only aceclofenac. The trials show that patients treated with the combination of aceclofenac and methionine show no changes in levels of SGPT and SGOT or they were within specified limits. However, a rise in SGPT and SGOT levels were observed in patients treated only with aceclofenac. In addition, surprisingly, it was observed that patients on a therapy of only aceclofenac showed decrease in the levels of SGPT and SGOT when the therapy was shifted to the combination of aceclofenac and methionine duet to the revitalizing of the liver by
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the combination. It is observed that the administration of mehionine in combination with aceclofenac actually mitigates the hepatotoxic effect of aceclofenac.
The invention is illustrated more in detail in the following examples. The examples describe and demonstrate embodiments within the scope of the present invention. These examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without departing from the spirit and scope. Tablet:

Example 1:
No. Ingredient Quantity (mg/Tablet)
1 Aceclofenac 100
2. Mehionine 50
3 Excipients q.s.
4 Colour & Flavor q.s.
5' Diluent q.s.

Example 2:
No. Ingredient Quantity (mg/Tablet)
1 Aceclofenac 100 SR
2. Mehionine 100
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3 Excipients q.s.
4 Colour & Flavor q.s.
5 Diluent q.s.

Example 3:
No. Ingredient Quantity (mg/Tablet)
1 Aceclofenac 200 SR
2. Mehionine 100
3 Excipients q.s.
4 Colour & Flavor q.s.
5 Diluent q.s.

Capsule
Example 4:
No. Ingredient Quantity (mg/Tablet)
1 Aceclofenac 100
2. Mehionine 50
3 Excipients q.s.
4 Diluent q.s.

Example 5:
No. Ingredient Quantity (mg/Tablet)
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1 Aceclofenac 100 SR
2. Mehionine 100
3 Excipients q.s.
4 Diluent q.s.

Example 6:
No. Ingredient Quantity (mg/Tablet)
1 Aceclofenac 200 SR
2. Mehionine 100
3 Excipients q.s.
4 Diluent q.s.
Oral Liquid Suspension

Example 7:
No. Ingredient Quantity (mg/Tablet)
1 Aceclofenac 100
2. Mehionine 50
3 Excipients q.s.
4 Colour & Flavor q.s.
5 Diluent q.s.
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Example 8:
No. Ingredient Quantity (mg/Tablet)
1 Aceclofenac 100 SR
2. Mehionine 100
3 Excipients q.S.
4 Colour & Flavor q.S.
5 Diluent q.s.

Example 9:
No.. Ingredient Quantity (mg/Tablet)
1 Aceclofenac 200 SR
2. Mehionine 100
3 Excipients q.s.
4 Colour & Flavor q.s.
5 Diluent q.s.
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claim:
1. A pharmaceutical composition comprising of acelofenac and methionine in a ratio of 1:1 to 2:1 being in terms of weight respectively, and the balance if any comprising one or more conventional additives.
2. A composition as claimed in claim 1 wherein the aceclofenac is used as such or in a polymeric form thereof and wherein the mehtionine is selected form the L isomer, the D isomer or a racemic mixture thereof.
3. A composition as claimed in claim 1 wherein the composition is in the form of a tablet, an oral suspension or a capsule.
4. A composition as claimed in any preceding claim wherein the conventional ingredients are selected from the group of consisting of diluents, disintegrants, colorants, flavoring agents, suspending agents and other conventional additives.
5. A composition as claimed in claim 3 wherein the oral liquid suspension form comprises of aceclofenac in an amount of 100 mg to 200 mg and mehtionine in an amount of 50 mg to 100 mg per 5 ml of dosage.
6. A method for the preparation of a pharmaceutical composition comprising of acelofenac and methionine in a ratio of 1:1 to 2:1 all ratios being in terms of weight respectively, and the balance if any comprising one or more conventional additives, said method comprising subjecting said aceclofenac to conventional methods of tableting, capsule formation or suspension.
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7. A pharmaceutical composition substantially as described herein before and with reference to the foregoing examples.
8. A method for the preparation of a pharmaceutical composition substantially as described herein before and with reference to the forgoing examples.
Dated this 16th day of March 2007.


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Dr. Rajeshkumar H. Acharya
Advocate & Patent Agent
For & on behalf of the Applicant.

ABSTRACT
The present invention relates to formulation containing aceclofenac and methionine in which methionine (its isomers and/or racemic mixture) prevents the hepatototic effects of aceclofenac. Methionine also revitalizes the liver in case of hepatotoxicity of aceclofenac. The oral dosage forms containing Methionine and aceclofenac together in various concentrations are developed as tablets, capsules and suspension.