FORM2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
"CARRAGEENAN BASED AQUEOUS COMPOSITIONS"
i
AJANTA PHARMA LTD.
A company incorporated under the laws of India having their office at
98, Ajanta house, Charkop, Kandivali (West)
Mumbai - 400067, Maharashtra, India.
The following specification particularly describes the invention and the manner in which it is to be performed.

TECHNICAL FIELD OF THE INVENTION;
The present invention relates to aqueous compositions of carrageenan its process for preparation and use of such a composition for the treatment of inflammatory and other diseases.
BACKGROUND OF INVENTION
Carrageenans are a group of naturally occurring family of hydrophilic polysaccharides extracted from certain species of red seaweed. They are high molecular weight, highly sulfated, linear molecules with a galactose backbone and are made up of sulfated and non-sulfated repeating units of galactose and 3, 6-anhydrogalactose.
Although there are at least ten different types of carrageenan known to be extracted from seaweed. From a commercial perspective, there are three main types widely used in industry, which includes iota, kappa and lambda carrageenan. These carrageenans are different from each other in both their structure and the number of sulfate groups. They are differentiated from each other by the amount of 3, 6-anhydrogalactose as well as the number and position of ester sulfate groups present (Edisson M; Carrageenan: drug delivery systems and other biomedical applications; Mar. Drugs 2020, 18, 583; page 3; para 2.1)
The traditional use of Carrageenans was as gelling agents in food products. However, more recently Carrageenans have been tested for use in the pharmaceutical industry, showing an association with improved drug formulations, such as sustained release formulations, and in the production of biomaterials (Jingjing Liu, Review for carrageenan-based pharmaceutical biomaterials: Favourable physical features versus adverse biological effects, Carbohydrate Polymers, Page 28; page 28).
US 20080131454 discloses use of carrageenan as an active antiviral ingredient in the manufacture of a pharmaceutical composition for the prophylactic or therapeutic treatment of a rhinovirus infection.
US 2020276226 discloses irrigation solution prepared by combining kappa carrageenan in an isotonic carrier solution comprising NaCl and KC1 for nasal and sinus use .This composition is administered in large volume (e.g. 100-200 ml) of carrier solution and is provided as a powder or a liquid solution.

US 2019060358 discloses hyperosmolar aqueous solution of carrageenan such as nasal spray for treatment of nasal decongestion, respiratory viral infection. The aqueous solution comprises a carrageenan component with non-ionic osmolality adjusting agent (7 % to 10% of sorbitol) and combination with an ionic osmolality adjusting agent (0.5% NaCl). The solution is stabilized with buffer and EDTA.
The present invention relates to an aqueous composition of carrageenan that is stable and can be used for the treatment of inflammatory and other diseases.
SUMMARY OF INVENTION:
The present invention is drawn to an aqueous composition comprising carrageenan for treatment of inflammatory and other diseases wherein said composition comprising one or more non-ionic osmolality adjusting agent, ionic osmolality adjusting agent and a pharmaceutically acceptable excipient.
The composition of the present invention is a stable aqueous composition. Specifically, the present invention further provides an aqueous pharmaceutical composition comprising carageenans. It is another object of the present invention to provide a method for preparing said compositions. In yet another object, the present invention also provides a process of preparing said composition.
DETAILED DESCRIPTION OF INVENTION
The present invention provides aqueous composition comprising carrageenan, its process for preparation and use of such composition for the treatment of inflammatory and other diseases.
In one embodiment, the present invention provides an aqueous composition comprising carrageenans, wherein said composition comprises one or more non-ionic osmolality adjusting agent, ionic osmolality adjusting agent and a pharmaceutically acceptable excipient wherein the non-ionic osmolality adjusting agent is present in an amount of about 0.1 % w/v to about 0.5 % w/v of composition.
The amount of non-ionic osmolality adjusting agent in the composition of the present invention may be in the range of about 0.01 % to about 0.4%, more preferably about 0.15% to about 0.3% and most preferably about 0.1% to about 0.25% by weight of the composition.
In another embodiment, the present invention provides an aqueous composition comprising carrageenans, wherein said composition comprises a non-ionic osmolality adjusting agent,

ionic osmolality adjusting agent and pharmaceutically acceptable excipients wherein the molar ratio of non-ionic osmolality adjusting agent to ionic osmolality adjusting agent is about 1:30 to about 1:45. In a preferred embodiment, the molar ratio of non-ionic osmolality adjusting agent to ionic osmolality adjusting agent is about 1:30 to about 1:35.
In yet another embodiment^ the present invention provides an aqueous composition comprising carrageenan, wherein said composition comprises one or more non-ionic osmolality adjusting agent, ionic osmolality adjusting agent and a pharmaceutically acceptable excipient wherein the osmolality of the solution is less than 300 mOsm/L.
The compositions of the present invention according to another embodiment of the invention generally has an osmolality in the range of 200 and 300m Osm/L, preferably the osmolality in the range of 220 and 290 mOsm/L more preferably between 230 and 280 mOsm/L, most preferably between 250 and 270 mOsm/L.
In further embodiment, the present invention provides an aqueous composition comprising carrageenan, wherein said composition comprises one or more non-ionic osmolality adjusting agent, ionic osmolality adjusting agent and a pharmaceutically acceptable excipient wherein the composition does not comprises an EDTA.
It has now been surprisingly found that a mixture of carrageenan with non-ionic osmolality adjusting agent in the range of about 0.1 % w/v to about 0.3 % w/v with osmolality below 300 mOsm/L are found suitable to be utilized in the preparation of novel, stable aqueous compositions of the invention.
Accordingly, the present invention is directed to an aqueous anti-inflammatory composition, comprising carrageenans (referred to herein as "the carrageenans" or a "carrageenan mixture") the carrageenan compositions may comprise either or both iota carrageenan and kappa carrageenan. In a preferred embodiment, the aqueous composition of the present invention comprises a mixture of Iota and kappa carrageenan.
The total amount of carrageenan present in the composition may be from about 0.01% to about 0.5%. In a preferred embodiment, the total amount of carrageenan or a pharmaceutically salt thereof may be about 0.04% to about 0.3% by weight of the composition. The amount of kappa carrageenan may be about 0.1% to about 0.5 % and iota carrageenan may be about 0.01 % to about 0.1%. In a preferred embodiment, the amount of kappa carrageenan may be about 0.1% to about 0.3 % and iota carrageenan may be about 0.01 % to about 0.5%.

The non-ionic osmolality adjusting agent according to the present invention may be selected from one or more of glycerol, erythritol, mannitol, sorbitol, inositol, xylitol, threitol, and maltitol. The most preferred non-ionic osmolality adjusting agent is sorbitol.
The Ionic osmolality adjusting agent according to the present invention may be selected from one or more of sodium chloride, potassium chloride, dextrose or mixture thereof.
The amount of ionic osmolality adjusting agent in the composition of the present invention may be in the range of about 0.1 % to about 0.4 %, preferably about 0.15% to about 0.3% and most preferably about 0.2% to about 0.3% by weight of the composition
The pharmaceutically acceptable excipients that may be used according to the present invention may be selected from one or more of preservatives, buffering agents or mixture thereof, wherein the composition does not comprises an EDTA.
Suitable preservatives that may be used according to the present invention are parabens, phenyl ethyl alcohol, benzalkonium chloride, benzyl alcohol or mixture thereof. In a preferred embodiment, the preservatives is paraben. In a most preferred embodiment, the preservatives is sodium methyl paraben and sodium propyl paraben. The amount of preservatives may be in the range of about 0.01% to about 0.5% preferably about 0.01% to about 0.3% and most preferably about 0.01 % to about 0.2% by weight of the composition.
Suitable buffering agents that may be used according to the present invention are from disodium hydrogen phosphate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, boric acid, borax, sodium acetate, citric acid, sodium citrate and sodium glutamate or mixture thereof. In a preferred embodiment, the buffering agent is disodium hydrogenphosphate or citric acid or a combination of both is used. The amount of buffering agent present in the composition ranges of about 0.01% to about 0.5% preferably about 0.1% to 0.4% and most preferably about 0.12% to about 0.4% by weight of the composition.
The composition of the present invention may be formulated in a suitable liquid dosage form including, but not limited to, a nasal spray, nasal drop or combinations thereof. In a preferred embodiment, the composition is in the form of nasal spray.
In another embodiment, the present invention relates to method of use of the pharmaceutical composition of the invention in the treatment of conditions such nasal allergy symptoms, nasal inflammation , nasal congestion, common cold and other diseases. The aqueous composition of the present invention doesnot causes nasal irritation.

In yet another embodiment the present invention provides process for preparing the aqueous composition. The aqueous composition of the present invention may be prepared by dissolving carrageenan in water, ionic osmolality adjusting agent and non ionic osmolality adjusting agent and subjecting it to filtration. Alternatively, the preparation can be done in sterile conditions using water for injection and sterile filtration . The aqueous solution of the present invention may be made for example by preparing an aqueous solution of carrageenan, preparation of aqueous solution of preservative , buffer and any other excipients followed by mixing the two solutions and aseptic filtration.
The following examples are set forth below to illustrate the methods and results according to the disclosed subject matter. These examples are not intended to be inclusive of all aspects of the subject matter disclosed herein, but rather to illustrate representative methods, compositions, and results. These examples are not intended to exclude equivalents and variations of the present invention, which are apparent to one skilled in the art.
Example 1

Sr
no Inactive ingredients
Weight percentage

Example 1 Example 2
Example 3
1 Kappa Carrageenan 0.12 0.12 0.12
2 Iota Carrageenan 0.04 0.04 0.04
3 Sodium methylparaben 0.03 0.04 0.03
4 Sodium propylparaben 0.02 0.18 0.17
5 Sodium chloride .0.28 0.28 0.28
6 Disodium hydrogen phosphate 1.12 1.12 1.12
7 Citric acid 0.4 0.4 0.39
8 Sorbitol 0.2 0.24 0.26
9 WFI q.s. q.s. q.s
Manufacturing process:
1: Preparation of carrageenan solution:
Water for injection (WFI) and weighed quantity of carrageenan in small proportion under continuous stirring until a clear solution was obtained followed by autoclaving and cooling the carrageenan solution.
Step II: Preparation of preservative and buffer solution:
Water for injection (WFI) and weighed quantity of sodium methylparaben, sodium propylparaben, sodium chloride, disodium hydrogen phosphate, citric acid, and sorbitol were added one by one under continuous stirring until a clear solution was obtained finally filter the solution using aseptic filtration.
Step III: Mixing carrageenan solution with preservative and buffer solution
Mixing step I and II followed by filtering the solution using aseptic filtration.

We Claim:
1. An aqueous composition of carrageenans comprising one or more non-ionic osmolality adjusting agent, ionic osmolality adjusting agent and other pharmaceutically acceptable excipients wherein the non-ionic osmolality adjusting agent is present in an amount of about 0.1 %w/v to about 0.3 %w/v by weight of composition.
2. An aqueous composition of carrageenans comprising one or more non-ionic osmolality adjusting agent, ionic osmolality adjusting agent and other pharmaceutically acceptable excipients wherein the molar ratio of non-ionic osmolality adjusting agent and ionic osmolality adjusting agent is about 1:30 to about 1:45.
3. An aqueous composition according to claim 1, comprising carrageenans wherein the osmolality of the solution is less than 300 mOsm/L.
4. An aqueous composition according to claim 1, comprising carrageenans that is selected from kappa carrageenan and/or iota carrageenan wherein the composition does not comprises an EDTA.
5. An aqueous composition according to claim 1, wherein the carrageenans is present in an amount of about 0.01% to about 0.5 % by weight of the composition.
6. An aqueous composition according to claim 1, wherein a non-ionic osmolality adjusting agent is selected from glycerol, erythritol, mannitol, sorbitol, inositol, xylitol, threitol, and maltitol or mixture thereof.

7. An aqueous composition according to claim 1, wherein the ionic osmolality adjusting agent is selected from sodium chloride, potassium chloride, dextrose or mixture thereof.
8. An aqueous composition according to claim 1, wherein the other pharmaceutically acceptable excipient comprises a preservative, buffering agent or mixture thereof.
9. An aqueous composition according to claim 6, wherein the preservatives selected from parabens, phenyl ethyl alcohol, benzalkonium chloride, benzyl alcohol or mixture thereof.
10. An aqueous composition according to claim 6, wherein the buffering agent selected from disodium hydrogen phosphate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, boric acid, borax, sodium acetate, citric acid, sodium citrate and sodium glutamate or mixture thereof.