FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule13)
1. TITLE OF THE INVENTION:
OPHTHALMIC COMPOSITION COMPRISING CARBOXYMETHYL CELLULOSE OR SALT THEREOF
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Wockhardt Towers, Bandra-Kurla Complex, Bandra
(East), Mumbai- 400 051.
3. PREAMBLE TO THE DESCRIPTION
The present invention provides ophthalmic composition comprising of carboxymethyl cellulose or salt thereof along with ophthalmically acceptable carriers.
The following specification particularly describes the invention and the manner in which it is to be performed.
1

4. Description
The present invention provides ophthalmic composition comprising of carboxymethyl cellulose or salt thereof along with ophthalmically acceptable carriers.
Carboxymethyl cellulose, is a cellulose derivative with carboxymethyl groups (-CH2-COOH) bound to some of the hydroxyl groups of the glucopyranose monomers that make up the cellulose backbone. The structural representation is provided in Formula 1. It is indicated for temporary relief of burning, irritation and discomfort due to dryness of the eye or due to exposure to wind or sun. Also may be used as protectant against further irritation.

7;"

'!_.. J\f
FORMULA 1
US Patent No. 7,045,121 provides ophthalmic composition comprising an ophthalmically acceptable carrier component; and a combination of polyanionic components.
US Patent No. 6,024,954 provides an ophthalmic composition comprising a liquid medium; a chlorite component and a polyanionic component in said liquid medium. The said composition having a viscosity of less than 50 cps at 25.degree. C. and an osmolality of at least about 200 mOsmol/kg.
2

US Patent No. 4,409,205 provides ophthalmic solution for use in normalizing irregularly structured tear films having an ionic salt ion content expressed as sodium chloride equivalents, and a viscosity within the range of from about 1 cps to 150 cps at 23.degree. C, comprising an aqueous solution of a water-soluble non-ionic synthetic polymer, and a non-ionic tonicity-adjusting agent.
US Patent No. 5,597,559 provides preservative-free ophthalmic composition, comprising hydroxyalkyl cellulosic polymer and polyalkylene glycol; a non-ionic tonicity adjusting agent, an ionic salt, and an antimicrobial in an amount sufficient to generate sufficient borate to maintain or reduce microbial concentrations for a period of 12 hours to 72 hours.
US Application No. 20050244509 provides an ophthalmic solution comprising a hydrogen peroxide source as a preservative; one or more ocularly compatible hydrogen peroxide stabilizers; hydroxypropylmethylcellulose; and sodium carboxymethylcellulose.
The present invention now provides stable ophthalmic composition comprising carboxymethyl cellulose or salt thereof along with ophthalmically acceptable carriers wherein the ophthalmic composition comprises phenylmercuric nitrate as a preservative.
In one of the aspects of the present invention there is provided an ophthalmic composition comprising carboxymethyl cellulose or salt thereof along with ophthalmically acceptable carriers wherein the ophthalmic composition comprises phenylmercuric nitrate as a preservative.
Preservative-free products may prevent the toxic side effects associated with preserved preparations, but there are some disadvantages. Preservative-free products are available only in unit dose vials that may be cumbersome to use and hinder compliance.
3

Preservatives are needed in multidose containers because bacterial contamination occurs with use at least twice daily for one to two weeks. Preservative is used generally to maintain a nonhazardous level of contamination in the composition. The result has been that preservatives in ophthalmic solutions have decreased the incidence of ocular infection because preservatives provide a level of antimicrobial activity in the bottle and limit bacterial and mycotic ocular infections caused by contaminated solutions. Preservatives also prolong the shelf life of the formulation by preventing biodegradation and maintaining drug potency.
In case of ophthalmic preservatives, benzalkonium chloride is the most frequently used preservative. But there are some disadvantages associated with the use of benzalkonium chloride. Topical application of benzalkonium chloride results in marked cytotoxic effects, which may be due to breakdown of the anatomical barrier in the outer layers of the corneal epithelium. Patients who may be at greater risk of benzalkonium chloride-induced adverse effects are those with dry-eye syndrome.
When phenylmercuric nitrate is used as preservative in the ophthalmic composition comprising carboxymethylcellulose or salt thereof it provides stable formulation. The phenylmercuric nitrate reacts with membrane sulfhydryl groups, resulting in increase in membrane permeability and alterations of membrane transport systems and thereby imparting antimicrobial action. Thus phenylmercuric nitrate proves to be an efficient preservative for carboxymethyl cellulose sodium containing ophthalmic composition.
The ophthalmic composition can be prepared by using ophthalmically acceptable carrier components. Ophthalmically acceptable carriers can be chelating agent, tonicity adjusting agent, buffering agent.
4

The chelating agent is a compound that is capable of complexing a metal, as understood by those of ordinary skill in the chemical art. Chelating agents are used in ophthalmic compositions to enhance preservative effectiveness. Some useful chelating agents for the purposes of this invention are edetate salts like edetate disodium, edetate calcium disodium, edetate sodium, edetate trisodium, and edetate dipotassium. In this invention edetate disodium is used as the chelating agent.
Tonicity adjusting agents are used in ophthalmic compositions to adjust the concentration of dissolved material to the desired isotonic range. Some examples include mannitol, sorbitol, sodium chloride, sodium borate, and the like and the mixtures thereof.
The present ophthalmic composition may be prepared by mixing all the carrier components into a suitable solvent. Further adding carboxymethyl cellulose or salt thereof into this mixture. Adjusting the pH of the composition with suitable pH adjusting agent and further filtering the solution with membrane filter.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art
Examples- Following formulations are representatives of the preferred compositions of the present invention. The preparation of example 1 is detailed below.
5

Example 1 -
Table 1 - Ophthalmic composition comprising Carboxymethylcellulose sodium

Sr.No Ingredients Qty in %
1 Carboxymethylcellulose sodium 7LF 0.5-1.0
2 Boric acid 0.15-1.5
3 Magnesium chloride 0.01-0.1
4 Potassium chloride 0.1 -0.5
5 Calcium chloride 0.05- 0.5
6 Phenylmercuric Nitrate 0.001 - 0.004
7 Sodium borate Qs
8 Sodium chloride Qs
9 Purified water Qs to100%
Procedure:
Carboxymethylcellulose sodium is mixed with the solvent with vigorous stirring. To this solution Boric acid, Magnesium chloride, Calcium chloride and Potassium chloride are added and dissolved properly. Phenylmercuric Nitrate is dissolved in solvent and mixed properly. pH is adjusted with pH adjusting agents. The composition is further filtered through 2.0 µ and 0.22 µ filter and filled in the suitable container.
6

WE CLAIM:
1. An ophthalmic composition comprising carboxymethyl cellulose or salt thereof along with ophthalmically acceptable carriers wherein the ophthalmic composition comprises phenylmercuric nitrate as a preservative.
2. An ophthalmic composition according to claim 1, wherein the carboxymethyl cellulose is present in the form of carboxymethyl cellulose sodium.
3. Ophthalmic composition according to claim 1, wherein the carrier component comprises water.
4. Ophthalmic composition according to claim 1, wherein the concentration of phenylmercuric nitrate is from 0.001-0.004%
5. Ophthalmic composition according to claim 1 further comprises chelating agent, tonicity adjusting agent, buffer component.
6. Ophthalmic composition according to claim 5, wherein the chelating agents comprises of edetate disodium, edetate calcium disodium, edetate sodium, edetate trisodium, edetate dipotassium and the like.
7. Ophthalmic composition according to claim 5, wherein the tonicity adjusting agents comprises of mannitol, sorbitol, sodium chloride, other electrolytes and the like.
7

8. Ophthalmic composition according to claim 5, wherein the buffer component comprises of boric acid, potassium chloride and the like.

Dated this 29TH day of September, 2006 For Wockhardt Limited

8

(Mandar Kodgule) Authorized Signatory