Title of Invention	A THERAPEUTIC COMPOSITION FOR TOPICAL APPLICATION TO FACILITATE HEALING OF WOUNDS AND PROCESS FOR PREPARING THE SAME
Abstract	A therapeutic composition suited both for medical and veterinary applications and capable of facilitating healing of wounds and simultaneously preventing bacterial, fungal and viral infections comprising - (i) a sucrose complex like sucralfate/sucrose octa acetate/sucrose octa sulphate, (ii) a nitroimidazole derivative like tinidazole or ornidazole and (iii) a compound providing free iodine such as povidone iodine or cadexomer iodine, in a suitable non-aqueous base like propylene glycol, "PEG-400" and "PEG-4000" (polyethylene glycols), characterized in that the aforesaid ingredients are present in the following amounts in the final composition - (i) sucralfate/sucrose octasulfate/sucrose octaacetate - 7.0-7.5% w/w, (ii) nitroimidazole derivative like tinidazole/ornidazole - 0.99 - 1.25 % w/w and (iii) free iodine from Povidone iodine or cadexomer iodine - 5 - 6 % w/w (providing 0.5 % available iodine)

Title of Invention

A THERAPEUTIC COMPOSITION FOR TOPICAL APPLICATION TO FACILITATE HEALING OF WOUNDS AND PROCESS FOR PREPARING THE SAME

Abstract

A therapeutic composition suited both for medical and veterinary applications and capable of facilitating healing of wounds and simultaneously preventing bacterial, fungal and viral infections comprising - (i) a sucrose complex like sucralfate/sucrose octa acetate/sucrose octa sulphate, (ii) a nitroimidazole derivative like tinidazole or ornidazole and (iii) a compound providing free iodine such as povidone iodine or cadexomer iodine, in a suitable non-aqueous base like propylene glycol, "PEG-400" and "PEG-4000" (polyethylene glycols), characterized in that the aforesaid ingredients are present in the following amounts in the final composition - (i) sucralfate/sucrose octasulfate/sucrose octaacetate - 7.0-7.5% w/w, (ii) nitroimidazole derivative like tinidazole/ornidazole - 0.99 - 1.25 % w/w and (iii) free iodine from Povidone iodine or cadexomer iodine - 5 - 6 % w/w (providing 0.5 % available iodine)

Full Text	The present invention relates to a therapeutic composition for topical application to facilitate healing of wounds and process for preparing the same. More particularly the subject invention pertains to a therapeutic composition capable of facilitating healing of wounds and simultaneously preventing bacterial, fungal and viral infections, comprising (i) source complexes selected from sucralfate, sucrose octasulphate and sucrose octaacetate, (ii) nitromidazole derivative like Tinidazole, Ornidazole, Secnidazole and Metronidazole, (iii) a compound providing free iodine such as povidone iodine, cadexomer iodine and potassium iodide and (iv) a stabilizer selected from Bronodiol, methyl paraben and/or propyl paraben and the composition is suitable for topical application. This invention also encompasses a process for preparing the above therapeutic composition, and constitutes an improvement in or modification of the invention described and claimed in the main Patent No.236701 (296/KOL/2005) dated 11.04.2005. In the aforesaid main Patent there is described and claimed a therapeutic composition for topical application to facilitate healing of wounds and prevent bacterial, fungal and viral infections comprising (a) sucralfate, (b) metronidazole and (c) povidone iodine as active ingredients in suitable non- aqueous base like propylene glycol, 'PEG-400' and 'PEG-4000' (polyethylene glycols), characterized in that the said active ingredients are present in the following amounts in the final composition : The said main Patent also disclosed a process for preparing the aforesaid therapeutic composition for topical application, which comprises - (a) mixing povidone-iodine and metronidazole, followed by addition of sucralfate, and continuing mixing till formation of an emulsion under anaerobic condition, followed by homogenization ; (b) melting propylene glycol, "PEG-400" and "PEG-4000" (polyethylene glycols) in steam-jacketed kettle to form an oil phase ; (c) the solid phase of step (a) and oil phase of step (b) are mixed properly with the help of a pump and mixer unit; (d) cooling the mixture, storing in a stainless steel container, filling the semi-solid mass in suitable container by filling machine and sealing the same. It has surprisingly been observed that by substituting "metronidazole" by Tinidozole", and in certain instances by replacing "povidone-iodine", the subject invention demonstrates remarkable effects in the treatment of wounds of skin, such as abrasion of skin, wounds and different types of skin ulcers, apart from healing of wounds and preventing bacterial, fungal and/or viral infections generally associated with the wounds. Previously wound management/treatment was primarily done by topical application of cream/lotion/powder of anti-biotic/anti-septic preparation and in majority of instances such treatment did not provide complete healing of wounds. Present day preparations available in the market are usually on the basis of a single drug, which takes care only of bacterial infection. Further, if a portion of a skin tissue has been damaged by an injury or burn or due to other reasons ( such as chemical or radioactive burn ), it is of utmost importance to repair and heal the damaged portion expeditiously. The present invention aims at overcoming the shortcomings and disadvantages of conventional mode of treatment as narrated above, and is concerned with therapeutic compositions for treating a wide variety of skin ulcers, particularly suited for medical and veterinary applications. The principal object of this invention is to provide a therapeutic composition for topical application to facilitate healing of wounds and prevent bacterial, fungal and viral infections generally associated with wounds. Another object of this invention is to provide a composition for treating wide variety of skin ulcers, and particularly suited for both medical and veterinary applications. Yet another object of this invention is to provide a therapeutic composition for treating a wide variety of skin ulcers and skin ailments and promoting healing of any open ulcer, and particularly suited for both medical and veterinary applications. A still another object of this invention is to provide a composition for promoting healing of surgical wounds, bites, burns, injury from chemicals, abrasions, lacerations and malodorous wounds. A further object of this invention is to provide a therapeutic composition which promotes healing of diabetic ulcers, decubitus ulcers, radiotherapy ulcers and chronic ulcerative wounds. A still further object of this invention is to provide a therapeutic composition for treating wide variety of damaged skin conditions like radiation induced mucositis, proctitis, excoriation of skin tissue, aphthous ulcer, stomatitis, diaper rash, perianal excoriation, anal fissures, ano-rectal excoriation, solitary rectal ulcer syndrome and the like. The foregoing objects are achieved by the present invention which relates to a therapeutic composition suited suited both for medical and veterinary application a therapeutic composition suited both for medical and veterinary applications and capable of facilitating healing of wounds and simultaneously preventing bacterial, fungal and viral infections comprising - (i) a sucrose complex like sucralfate /sucrose octa acetate /sucrose octa sulphate, (ii) a nitroimidazole derivative like tinidazole or ornidazole and (iii) a compound providing free iodine such as povidone iodine or cadexomer iodine, in a suitable non-aqueous base like propylene glycol, 'PEG-400' and 'PEG-4000' (polyethylene glycols), characterized in that the aforesaid ingredients are present in the following amounts in the final composition - (i) sucralfate/sucroseoctasulfate/sucroseoctaacetate - 7.0-7.5% w/w, (ii) nitroimidazole derivative like tinidazole/ornidazole - 0.99 - 1.25% w/w and (iii) free iodine from Povidone iodine or cadexomer iodine - 5 - 6 % w/w (providing 0.5 % available iodine) In the composition as disclosed above, propylene glycol acts as the humactant and there is also used a stabilizer selected from the group of "Bronopol", methyl paraben and propyl paraben for enhancing its shelf life. The amount of stabilizer added to the composition in the course of mixing of different phases containing constituent ingredients usually around 1% w/w of the final composition. The subject invention also pertaining to a process for preparing the aforementioned composition, which comprises - (i) preparation of solid phase by mixing of predetermined amounts of different ingredients; (ii) homogenization of solid phase in a suitable homogenizer; (iii) preparation of oil phases by heating propylene glycol, PEG-400 and PEG-4000 in a stainless steel steem jacketed kettle at a temperature of around 60°C and transferring the oil phase to a mixing kettle ; (iv) mixing of solid and oil phases at a temperature of around 70°C with the help of a pump and mixer with addition of stabilizer for enhancement of shelf life of the composition ; (v) cooling the mixture by gradually decreasing the temperature of the jacketed kettle at a rate consisting with the mixing of the emulsion ; (vi) storage of finished phase is done in a stainless steel container of suitable size; (vii) transfer of semi-solid material is done from the container to the ointment filling machine for being filled in suitable contaners/receptacles/collapsible tubes followed by proper sealing. In a further embodiment of the above process, the constituent ngredients are added/dispersed in oil phases and any undispersed matter is emoved by passing it through a 40-mesh screen and cooling of the semi-solid product is carried out in steam-jacketed kettle, the walls of which are so designed hat they prevent formation of congealed substances. In another embodiment of the above process, preparation of oil phase s carried out by mixing "PEG-400" and "PEG-4000" and heating the mixture to a emperature of 70°C, transferring the mass to a container at 70°C through 40- nesh screen, preparing slurries of ingredients separately in 'PEG-400', cooling he container to around 40°C while mixing them under stirring and washing the esulting thick mass to remove excess iodine, stirring the semi-solid mass under vacuum, followed by storage and transfer of semi-solid finished product for filling nto containers, sealing and packing, or for packing into bulk containers. As discusssed above, the subject composition has been found to be :xtremely effective in providing immediate relief from pain and long lasting healing )f ulcer/skin lesions and employs as active principles the following compounds n predetermined amounts: a) sucralfate (or other similar complexes, e.g. sucrose octasulfate, sucrose octaacetate and the like); b) compound providing free iodine, e.g. povidone iodine, cadexomer iodine, potassium iodine, etc.; c) a nitroimidazole derivative, e.g. metronidazole, tinidazole, secnidazole, ornidazole, satranidazole, carnidazole, nimorazole, benznidazole, misonidazole, and the like. It has suprisingly been found that using alternative ingredients, )articularly tinidazole', the efficacy of the composition is enhanced manifold. The invention will now be further amplified by means of the following Example', which are given by way of illustration and not by way of limitation : Example 1 BATCH SIZE-10 KG 1. MIXING:- 0.50 kg Povidone-Iodine and 0.11 kg Tinidazole is mixed in a suitable mixer. The angle of entry of the propeller shaft and the depth of the propeller is adjusted. A metal spatula is held in position to increase the turbulence to provide better mixing. 0.75 Kg of Sucralfate is added and mixed. Aeration has been avoided to provide stable emulsion. 2. HOMOGENIZATION:- The mixing material is homogenized in a suitable homogenizer to achieve a product of required viscosity at 2000psi. 3. PREPARATION OF OIL PHASES:- Propylene glycol 1 Kg i.e., humactant and PEG 400 - 5 litres and PEG 4000 - 3 litres are placed in stainless steel steam jacketed kettle, melted at a temperature 60° C. The oil phase transferred by gravity to emulsifying mixing kettle. 4. MIXING OF PHASES:- The solid phase and oil phase are mixed at a temperature of 70° C and this process is done by the use of suitable pump and a suitable mixer. Stabilizer - Bronodiol 1% w/w or Methyl Paraben 1% w/w or Propyl Paraben 1% w/w may be used to enhance its shelf-life. 5. COOLING PHASE:- The temperature of the kettle jacket is decreased gradually at a rate consistent with the mixing of the emulsion and the pressure generated inside the jacked kettle is 70psi and preparation of kettle wall is done to prevent formation of congealed substances. 6. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 7. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 8. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 2 BATCH SIZE-100 KG 1. MIXING:- 6 kg Povidone-Iodine and 1.05 kg Tinidazole is mixed in a suitable mixer. The angle of entry of the propeller shaft and the depth of the propeller is adjusted. A metal spatula is held in position to increase the turbulence to provide better mixing. 7.35 Kg of Sucralfate is added and mixed. Aeration is avoided to provide stable emulsion. 2. HOMOGENIZATION:- The mixing material is homogenized in a suitable homogenizer to achieve a product of required viscosity at 2000psi. 3. PREPARATION OF OIL PHASES:- Propylene glycol 10 Kg i.e., humactant and PEG 400 - 48 litres and PEG 4000 - 28 litres are placed in stainless steel steam jacketed kettle, melted at a temperature 60 C. The oil phase transferred by gravity to emulsifying mixing kettle. 4. MIXING OF PHASES:- The solid phase and oil phase are mixed at a temperature of 70° C and this process is done by the use of suitable pump and a suitable mixer. 5. COOLING PHASE:- The temperature of the kettle jacket is decreased gradually at a rate consistent with the mixing of the emulsion and the pressure generated inside the jacked kettle is 70psi and preparation of kettle wall is done to prevent formation of congealed substances. Stabilizer - Bronodiol 1% w/w or Methyl Paraben 1% w/w or Propyl Paraben 1% w/w may be used to enhance its shelf-life. 6. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 7. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 8. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 3 BATCH SIZE-50 KG 1. MIXING:- 3 kg Povidone-Iodine and 0.55 kg Tinidazole is mixed in a suitable mixer. The angle of entry of the propeller shaft and the depth of the propeller is adjusted. A metal spatula is held in position to increase the turbulence to provide better mixing. 3.70 Kg of Sucralfate is added and mixed. Aeration has been avoided to provide stable emulsion. 2. HOMOGENIZATION:- The mixing material is homogenized in a suitable homogenizer to achieve a product of required viscosity at 2000psi. 3. PREPARATION OF OIL PHASES:- Propylene glycol 5 Kg i.e., humactant and PEG 400 - 25 litres and PEG 4000 - 15 litres are placed in stainless steel steam jacketed kettle, melted at a temperature 60° C. The oil phase transferred by gravity to emulsifying mixing kettle. 4. MIXING OF PHASES:- The solid phase and oil phase are mixed at a temperature of 70° C and this process is done by the use of suitable pump and a suitable mixer. . 5. COOLING PHASE:- The temperature of the kettle jacket is decreased gradually at a rate consistent with the mixing of the emulsion and the pressure generated inside the jacked kettle is 70psi and preparation of kettle wall is done to prevent formation of congealed substances. Stabilizer - Bronodiol 1% w/w or Methyl Paraben 1% w/w or Propyl Paraben 1% w/w may be used to enhance its shelf-life. 6. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless ' steel container of suitable size. 7. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 8. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 4 BATCH SIZE-10 KG 1. PART-1:- PEG 400 3 kg is taken and Povidone-Iodine 0.5 kg is added slowly with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -1.9kg & PEG 400 -2.7 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucralfate 0.75 kg and PEG 400 -0.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Tinidazole 0.11 kg and PEG 400 -0.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Povidone Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 5 BATCH SIZE-100 KG 1. PART-1:- PEG 400 30 kg is taken and Povidone-Iodine 6 kg is added slowly with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -19kg & PEG 400 -27 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucralfate 7.35 kg and PEG 400 -5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Tinidazole 1.05 kg and PEG 400 -5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Povidone Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 6 BATCH SIZE-50 KG 1. PART-1:- PEG 400 15 kg is taken and Povidone-Iodine 3 kg is added slowly with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -9.5 kg & PEG 400 -13.5 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucralfate 3.70 kg and PEG 400 -2.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Tinidazole 0.55 kg and PEG 400 -2.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Povidone Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 7 BATCH SIZE-10 KG 1. PART-1:- PEG 400 3 kg is taken and Povidone-Iodine 0.5 kg is added slowly with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -1.9kg & PEG 400 -2.7 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucralfate 0.75 kg and PEG 400 -0.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Ornidazole 0.11 kg and PEG 400 -0.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Povidone Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. BATCH SIZE-100 KG Example 8 1. PART-1:- PEG 400 30 kg is taken and Povidone-Iodine 6 kg is added slowly with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -19kg & PEG 400 -27 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucrose octasulfate 7.35 kg and PEG 400 -5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Tinidazole 1.05 kg and PEG 400 -5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Povidone Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 9 BATCH SIZE-50 KG 1. PART-1:- PEG 400 15 kg is taken and Povidone-Iodine 3 kg is added slowly with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -9.5 kg & PEG 400 -13.5 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucralfate 3.70 kg and PEG 400 -2.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Ornidazole 0.55 kg and PEG 400 -2.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Povidone Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 10 BATCH SIZE-10 KG 1. PART-1:- PEG 400 3 kg is taken and Cadexomer Iodine 0.56 kg is added slowly with manual stirring to make a slurry. Cadexomer Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -1.9kg & PEG 400 -2.7 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucralfate 0.75 kg and PEG 400 -0.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Tinidazole 0.11 kg and PEG 400 -0.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Cadexomer Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Cadexomer Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 11 BATCH SIZE-100 KG 1. PART-1:- PEG 400 30 kg is taken and Cadexomer Iodine 5.56 kg is added slowly with manual stirring to make a slurry. Cadexomer Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -19kg & PEG 400 -27 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucralfate 7.35 kg and PEG 400 -5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Tinidazole 1.05 kg and PEG 400 -5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Cadexomer Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Cadexomer Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 12 BATCH SIZE-50 KG 1. PART-1:- PEG 400 15 kg is taken and Cadexomer Iodine 3.2 kg is added slowly with manual stirring to make a slurry. Cadexomer Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -9.5 kg & PEG 400 -13.5 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucralfate 3.70 kg and PEG 400 -2.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Tinidazole 0.55 kg and PEG 400 -2.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Cadexomer Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Cadexomer Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 13 BATCH SIZE-10 KG 1. PART-1:- PEG 400 3 kg is taken and Povidone-Iodine 0.5 kg is added slowly with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -1.9kg & PEG 400 -2.7 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucrose octasulfate 0.75 kg and PEG 400 -0.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Tinidazole 0.11 kg and PEG 400 -0.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Povidone Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 14 BATCH SIZE-100 KG 1. PART-1:- PEG 400 30 kg is taken and Povidone-Iodine 6 kg is added slowly with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -19kg & PEG 400 -27 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucrose octasulfate 7.35 kg and PEG 400 -5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Tinidazole 1.05 kg and PEG 400 -5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Povidone Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Example 15 BATCH SIZE-50 KG 1. PART-1:- PEG 400 15 kg is taken and Povidone-Iodine 3 kg is added slowly with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in PEG 400. 2. PART-2:- PEG 4000 -9.5 kg & PEG 400 -13.5 kg are mixed and heated upto 70°C. The slurry is transferred in a suitable container at 70°C passing through 40 mesh. 3. PART-3:- A slurry of Sucrose octasulfate 3.70 kg and PEG 400 -2.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 4. PART-4:- A slurry of Tinidazole 0.55 kg and PEG 400 -2.5 kg is prepared. It is passed through 40 mesh and added to container simultaneously. 5. MIXING: The container is being cooled gradually at temperature below 50°C. At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the container and it is stirred slowly for 3-4 hours with cooling. Thick mass preparation takes place and it is washed to reduce the concentration of Povidone Iodine. 6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum is released slowly and this process is repeated for 2-3 times. 7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless steel container of suitable size. 8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished phase is transferred to the filling equipment. 9. FILLING AND SEALING:- The semi-solid material are filled by suitable ointment filling machine into suitable containers and sealed properly. Certain test results based on experiments conducted in one of the leading Medical Colleges in Eastern India clearly establish the unexpectedness/ synergism exhibited by the therapeutic composition of this invention. It will be clear from the anti-bacterial spectrum of the individual drugs that the composition of this invention has greater clinical benefits as well as expanded anti-bacterial activity. Moreover, the subject composition shows anti-inflammatory (by blocking the inflammatory mediators) as well as regenerative properties (by binding EGF), and is well-tolerated with no contra- indications or side effects even after prolonged topical application. To evaluate the role of the therapeutic composition of the present invention containing tinidazole, sucralfate and povidone iodine in the healing process of post surgical and contaminated superficial wounds, studies were conducted with both indoor and outdoor patients of Department of Surgery at N.R.S. Medical College & Hospital in Kolkata. Patients receiving systemic (oral or i.v.) Tinidazole or Ornidazole were excluded from study. Example 16 30 patients were evaluated with surgical site infections, diabetic ulcers, ulcers due to peripheral vascular disease and super ficial epithetial breachers by topical application of the composition of this invention. Another 20 patients with same condistions were also evaluated with placebo ointments. All wounds were clinically assessed for general appearance, signs of infection, degree of exudation, skin maceration, wound size, and local pain. A culture sensitivity swab was taken before the application of ointment, and 7 and 14 days after the applicant of oinment. Treatment protocol: Wounds were cleansed with sterile normal saline before treatment. There were no forceful irrigation techniques and no other cleansing agents utilized. The same dressing technique was used throughout the study. It consisted of a non-adherent primary dressing and an absorbent secondary dressing. Treatment with the subject topical oinment was performed once daily. RESULTS :Results of the topical application were clinically assessed by general appearance of the wound, signs of infection, degree of exudation, skin maceration, wound size, and local pain. Culture swabs were taken from the wound. Out of the 30 patients, 17 patients showed signs of healthy granulation tissue within first 7 days, whereas in 9 patients the wounds became clean with diminished discharge within 14 days. 3 patients showed no improvement within 14 days and needed further surgical treatment. These 3 patients were suffering from peripheral vascular disease. 1 patient complain of itching over and around the wound. Out of the 20 patients treated with placebo ointment, 8 patients showed signs of healthy granulation tissue after 7 days, and 13 patients showed signs of improvements, whereas 7 patients showed no signs of healthy granulation tissue. EFFICACY OF FORMULATION IN CONTAMINATED WOUND MANAGEMENT CONCLUSIONS: 1. TOPICAL APPLICATION OF FORMULATION CONTAINING TINIDAZOLE, POVIDONE IODINE AND SUCRALFATE SHOWED A DEFINITE ROLE IN IMPROVING SUPERFICIAL WOUNDS BY CONTROLLING LOCAL INFECTIONS & AUGMENTING THE PROCESS OF HEALING. 2. THIS TREATMENT IS COST EFFECTIVE IN LONG TERM MANAGEMENT OF WOUNDS. 3. EFFECTIVE AS ANTIBIOTIC & TISSUE REGENERATIVE OINTMENT WITHOUT ANY MAJOR SIDE EFFECTS. From the foregoing discussions and data given hereinbefore it will be seen that: (i) the subject therapeutic composition of this invention is well-tolarated and the constituents drugs do not interfere with the bio availability of each other; (ii) no toxic drug interactions are involved with the constituent components ; (iii) the composition stimulates wounds healing by activating keratinocytes and fibroblast functions; (iv) the synergistic combination of the main ingredients effectively shows anti- microbial action against all possible aerobic and anaerobic micro-organisms present in the wounds ; (v) the regenerative and anti-inflammatory property of sucralfate accentuates anti-microbial and anti-viral perperties of the other two drugs by epithelialization and angiogenesis, and (vi) strengthening of exterior cell surface and connective tissue cell matrix makes it extremely difficult for bacteria and virus to penetrate and colonise the cells and the tissue. While the invention has been described in details and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without deviating or departing from the spirit and scope of the invention. Thus the disclosure contained herein includes within its ambit the obvious equivalents and substitutes as well. Having described the invention in detail with particular reference to the illustrative examples given abovem it will now be more specifically defined by means of claims appended hereafter. I claim : 1. A therapeutic composition suited both for medical and veterinary applications and capable of facilitating healing of wounds and simultaneously preventing bacterial, fungal and viral infections comprising - (i) a sucrose complex like sucralfate/sucrose octa acetate/sucrose octa sulphate, (ii) a nitroimidazole derivative like tinidazole or ornidazole and (iii) a compound providing free iodine such as povidone iodine or cadexomer iodine, in a suitable non-aqueous base like propylene glycol, 'PEG-400' and 'PEG-4000' (polyethylene glycols), characterized in that the aforesaid ingredients are present in the following amounts in the final composition - (i) sucralfate/sucrose octasulfate/sucrose octaacetate - 7.0-7.5% w/w, (ii) nitroimidazole derivative like tinidazole/ornidazole - 0.99 - 1.25 % w/w and (iii) free iodine from Povidone iodine or cadexomer iodine - 5 - 6 % w/w (providing 0.5 % available iodine) 2. A composition as claimed in Claim 1, wherein the ingredients are present in suitable non-aqueous/aqueous base like propylene glycol, 'PEG-400', *PEG-4000' (polyethylene glycols) and water, propylene glycol additionally acting as a humactant. 3. A composition as claimed in Claims 1 and 2, wherein the composition includes a stabilizer selected from the group of'Bronodiol', methyl paraben and propyl paraben, present in an amount not exceeding 1% w/w of the said composition. 4. A composition as claimed in Claims 1 to 3, wherein there is included medicaments/compounds which enhance Epidermal Growth Factor (EGF) and Fibroblast Growth Factor (FGF) for regeneration of damaged tissues, bioflavonoids, haemostatic agents and plant extracts for promoting better healing of skin ulcers. 5. A therapeutic composition suited both for medical and veterinary applications and simultaneously preventing bacterial, fungal and viral infections, substantially as hereinbefore described and illustrated by means of appended Examples. 6. A process for preparing a therapeutic composition suited both for medical and veterinary applications and simultaneously preventing bacterial, fungal and viral infections as claimed in any one of the preceding claims, which comprises - (i) preparation of solid phase by mixing of predetermined amounts of different ingredients; (ii) homogenization of solid phase in a suitable homogenizer; (iii) preparation of oil phases by heating propylene glycol, PEG-400 and PEG-4000 in a stainless steel steem jacketed kettle at a temperature of around 60°C and transferring the oil phase to a mixing kettle ; (iv) mixing of solid and oil phases at a temperature of around 70°C with the help of a pump and mixer with addition of stabilizer for enhancement of shelf life of the composition ; (v) cooling the mixture by gradually decreasing the temperature of the jacketed kettle at a rate consisting with the mixing of the emulsion ; (vi) storage of finished phase is done in a stainless steel container of suitable size; (vii) transfer of semi-solid material is done from the container to the ointment filling machine for being filled in suitable contaners/receptacles/collapsible tubes followed by proper sealing. 7. A process as claimed in Claim 6, wherein a stabilizer in an amount of 1% w/w of the final composition selected from the group of 'Bromodiol', methyl paraben or propyl paraben is added to the reaction medium during mixing of solid and oil phases. 8. A process as claimed in Claims 6 and 7, wherein the ingredients are added/ dispersed in oil phases and any undispersed matter is removed by passing it through a 40-mesh screen and cooling of the semi-solid product is carried out in steam jacketed kettle, the walls of which are so designed as to prevent formation of congealed substances. 9. A process as claimed in Claim 8, wherein preparation oil phase is carried out by mixing 'PEG-400' and PEG-4000' and heating the mixture to a temperature of 70°C, transferring the mass to a container at 70°C through 40 mesh screen, preparing slurrys of ingredients separetely in 'PEG-400', cooling the container to around 40°C while mixing them under stirring and washing the resulting thick mass to remove excess iodine, stirring the semi-solid mass under vacuum and thereafter releasing vacuum, followed by storage and transfer of finished product for silling into containers, sealing and packing or for packing into bulk containers. 10. A process for preparing a therapeutic composition suited both for medical and veterinary applications and simultaneously preventing bacterial, fungal and viral infections, substantially as hereinbefore described and illustrated in the Examples given hereinbefore. 1. A therapeutic composition suited both for medical and veterinary applications and capable of facilitating healing of wounds and simultaneously preventing bacterial, fungal and viral infections comprising - (i) a sucrose complex like sucralfate/sucrose octa acetate/sucrose octa sulphate, (ii) a nitroimidazole derivative like tinidazole or ornidazole and (iii) a compound providing free iodine such as povidone iodine or cadexomer iodine, in a suitable non-aqueous base like propylene glycol, 'PEG-400' and 'PEG-4000' (polyethylene glycols), characterized in that the aforesaid ingredients are present in the following amounts in the final composition - (i) sucralfate/sucrose octasulfate/sucrose octaacetate - 7.0-7.5% w/w, (ii) nitroimidazole derivative like tinidazole/ornidazole - 0.99 - 1.25 % w/w and (iii) free iodine from Povidone iodine or cadexomer iodine - 5 - 6 % w/w (providing 0.5 % available iodine)

Full Text

The present invention relates to a therapeutic composition for topical
application to facilitate healing of wounds and process for preparing the same.
More particularly the subject invention pertains to a therapeutic composition
capable of facilitating healing of wounds and simultaneously preventing bacterial,
fungal and viral infections, comprising (i) source complexes selected from sucralfate,
sucrose octasulphate and sucrose octaacetate, (ii) nitromidazole derivative like
Tinidazole, Ornidazole, Secnidazole and Metronidazole, (iii) a compound
providing free iodine such as povidone iodine, cadexomer iodine and potassium
iodide and (iv) a stabilizer selected from Bronodiol, methyl paraben and/or propyl
paraben and the composition is suitable for topical application.
This invention also encompasses a process for preparing the
above therapeutic composition, and constitutes an improvement in or modification
of the invention described and claimed in the main Patent No.236701
(296/KOL/2005) dated 11.04.2005.
In the aforesaid main Patent there is described and claimed a
therapeutic composition for topical application to facilitate healing of wounds
and prevent bacterial, fungal and viral infections comprising (a) sucralfate,
(b) metronidazole and (c) povidone iodine as active ingredients in suitable non-
aqueous base like propylene glycol, 'PEG-400' and 'PEG-4000' (polyethylene
glycols), characterized in that the said active ingredients are present in the
following amounts in the final composition :

The said main Patent also disclosed a process for preparing the
aforesaid therapeutic composition for topical application, which comprises -
(a) mixing povidone-iodine and metronidazole, followed by addition of
sucralfate, and continuing mixing till formation of an emulsion under
anaerobic condition, followed by homogenization ;
(b) melting propylene glycol, "PEG-400" and "PEG-4000" (polyethylene glycols)
in steam-jacketed kettle to form an oil phase ;
(c) the solid phase of step (a) and oil phase of step (b) are mixed properly with
the help of a pump and mixer unit;
(d) cooling the mixture, storing in a stainless steel container, filling the
semi-solid mass in suitable container by filling machine and sealing
the same.
It has surprisingly been observed that by substituting "metronidazole"
by Tinidozole", and in certain instances by replacing "povidone-iodine", the subject
invention demonstrates remarkable effects in the treatment of wounds of skin,
such as abrasion of skin, wounds and different types of skin ulcers, apart from
healing of wounds and preventing bacterial, fungal and/or viral infections
generally associated with the wounds.
Previously wound management/treatment was primarily done by
topical application of cream/lotion/powder of anti-biotic/anti-septic preparation
and in majority of instances such treatment did not provide complete healing of
wounds. Present day preparations available in the market are usually on the
basis of a single drug, which takes care only of bacterial infection. Further, if a
portion of a skin tissue has been damaged by an injury or burn or due to other
reasons ( such as chemical or radioactive burn ), it is of utmost importance to
repair and heal the damaged portion expeditiously. The present invention aims
at overcoming the shortcomings and disadvantages of conventional mode of
treatment as narrated above, and is concerned with therapeutic compositions for
treating a wide variety of skin ulcers, particularly suited for medical and veterinary
applications.
The principal object of this invention is to provide a therapeutic
composition for topical application to facilitate healing of wounds and prevent
bacterial, fungal and viral infections generally associated with wounds.
Another object of this invention is to provide a composition for treating
wide variety of skin ulcers, and particularly suited for both medical and veterinary
applications.
Yet another object of this invention is to provide a therapeutic
composition for treating a wide variety of skin ulcers and skin ailments and
promoting healing of any open ulcer, and particularly suited for both medical
and veterinary applications.
A still another object of this invention is to provide a composition for
promoting healing of surgical wounds, bites, burns, injury from chemicals,
abrasions, lacerations and malodorous wounds.
A further object of this invention is to provide a therapeutic
composition which promotes healing of diabetic ulcers, decubitus ulcers,
radiotherapy ulcers and chronic ulcerative wounds.
A still further object of this invention is to provide a therapeutic
composition for treating wide variety of damaged skin conditions like radiation
induced mucositis, proctitis, excoriation of skin tissue, aphthous ulcer, stomatitis,
diaper rash, perianal excoriation, anal fissures, ano-rectal excoriation, solitary
rectal ulcer syndrome and the like.
The foregoing objects are achieved by the present invention which
relates to a therapeutic composition suited suited both for medical and veterinary
application a therapeutic composition suited both for medical and veterinary
applications and capable of facilitating healing of wounds and simultaneously
preventing bacterial, fungal and viral infections comprising -
(i) a sucrose complex like sucralfate /sucrose octa acetate /sucrose octa
sulphate,
(ii) a nitroimidazole derivative like tinidazole or ornidazole and
(iii) a compound providing free iodine such as povidone iodine or cadexomer
iodine, in a suitable non-aqueous base like propylene glycol, 'PEG-400'
and 'PEG-4000' (polyethylene glycols), characterized in that the aforesaid
ingredients are present in the following amounts in the final composition -
(i) sucralfate/sucroseoctasulfate/sucroseoctaacetate - 7.0-7.5% w/w,
(ii) nitroimidazole derivative like tinidazole/ornidazole - 0.99 - 1.25% w/w and
(iii) free iodine from Povidone iodine or cadexomer iodine - 5 - 6 % w/w
(providing 0.5 % available iodine)
In the composition as disclosed above, propylene glycol acts as the
humactant and there is also used a stabilizer selected from the group of "Bronopol",
methyl paraben and propyl paraben for enhancing its shelf life. The amount of
stabilizer added to the composition in the course of mixing of different phases
containing constituent ingredients usually around 1% w/w of the final
composition.
The subject invention also pertaining to a process for preparing the
aforementioned composition, which comprises -
(i) preparation of solid phase by mixing of predetermined amounts of different
ingredients;
(ii) homogenization of solid phase in a suitable homogenizer;
(iii) preparation of oil phases by heating propylene glycol, PEG-400 and
PEG-4000 in a stainless steel steem jacketed kettle at a temperature
of around 60°C and transferring the oil phase to a mixing kettle ;
(iv) mixing of solid and oil phases at a temperature of around 70°C with the
help of a pump and mixer with addition of stabilizer for enhancement of
shelf life of the composition ;
(v) cooling the mixture by gradually decreasing the temperature of the jacketed
kettle at a rate consisting with the mixing of the emulsion ;
(vi) storage of finished phase is done in a stainless steel container of suitable
size;
(vii) transfer of semi-solid material is done from the container to the ointment
filling machine for being filled in suitable contaners/receptacles/collapsible
tubes followed by proper sealing.
In a further embodiment of the above process, the constituent
ngredients are added/dispersed in oil phases and any undispersed matter is
emoved by passing it through a 40-mesh screen and cooling of the semi-solid
product is carried out in steam-jacketed kettle, the walls of which are so designed
hat they prevent formation of congealed substances.
In another embodiment of the above process, preparation of oil phase
s carried out by mixing "PEG-400" and "PEG-4000" and heating the mixture to a
emperature of 70°C, transferring the mass to a container at 70°C through 40-
nesh screen, preparing slurries of ingredients separately in 'PEG-400', cooling
he container to around 40°C while mixing them under stirring and washing the
esulting thick mass to remove excess iodine, stirring the semi-solid mass under
vacuum, followed by storage and transfer of semi-solid finished product for filling
nto containers, sealing and packing, or for packing into bulk containers.
As discusssed above, the subject composition has been found to be
:xtremely effective in providing immediate relief from pain and long lasting healing
)f ulcer/skin lesions and employs as active principles the following compounds
n predetermined amounts:
a) sucralfate (or other similar complexes, e.g. sucrose octasulfate, sucrose
octaacetate and the like);
b) compound providing free iodine, e.g. povidone iodine, cadexomer iodine,
potassium iodine, etc.;
c) a nitroimidazole derivative, e.g. metronidazole, tinidazole, secnidazole,
ornidazole, satranidazole, carnidazole, nimorazole, benznidazole,
misonidazole, and the like.
It has suprisingly been found that using alternative ingredients,
)articularly tinidazole', the efficacy of the composition is enhanced manifold.
The invention will now be further amplified by means of the following
Example', which are given by way of illustration and not by way of limitation :
Example 1
BATCH SIZE-10 KG
1. MIXING:- 0.50 kg Povidone-Iodine and 0.11 kg Tinidazole is mixed in a
suitable mixer. The angle of entry of the propeller shaft and the depth of the
propeller is adjusted. A metal spatula is held in position to increase the
turbulence to provide better mixing. 0.75 Kg of Sucralfate is added and mixed.
Aeration has been avoided to provide stable emulsion.
2. HOMOGENIZATION:- The mixing material is homogenized in a suitable
homogenizer to achieve a product of required viscosity at 2000psi.
3. PREPARATION OF OIL PHASES:- Propylene glycol 1 Kg i.e., humactant
and PEG 400 - 5 litres and PEG 4000 - 3 litres are placed in stainless steel steam
jacketed kettle, melted at a temperature 60° C. The oil phase transferred by
gravity to emulsifying mixing kettle.
4. MIXING OF PHASES:- The solid phase and oil phase are mixed at a
temperature of 70° C and this process is done by the use of suitable pump and a
suitable mixer. Stabilizer - Bronodiol 1% w/w or Methyl Paraben 1% w/w or
Propyl Paraben 1% w/w may be used to enhance its shelf-life.
5. COOLING PHASE:- The temperature of the kettle jacket is decreased gradually
at a rate consistent with the mixing of the emulsion and the pressure generated
inside the jacked kettle is 70psi and preparation of kettle wall is done to prevent
formation of congealed substances.
6. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
7. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
8. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 2
BATCH SIZE-100 KG
1. MIXING:- 6 kg Povidone-Iodine and 1.05 kg Tinidazole is mixed in a suitable
mixer. The angle of entry of the propeller shaft and the depth of the propeller is
adjusted. A metal spatula is held in position to increase the turbulence to provide
better mixing. 7.35 Kg of Sucralfate is added and mixed. Aeration is avoided to
provide stable emulsion.
2. HOMOGENIZATION:- The mixing material is homogenized in a suitable
homogenizer to achieve a product of required viscosity at 2000psi.
3. PREPARATION OF OIL PHASES:- Propylene glycol 10 Kg i.e., humactant
and PEG 400 - 48 litres and PEG 4000 - 28 litres are placed in stainless steel
steam jacketed kettle, melted at a temperature 60 C. The oil phase transferred by
gravity to emulsifying mixing kettle.
4. MIXING OF PHASES:- The solid phase and oil phase are mixed at a
temperature of 70° C and this process is done by the use of suitable pump and a
suitable mixer.
5. COOLING PHASE:- The temperature of the kettle jacket is decreased gradually
at a rate consistent with the mixing of the emulsion and the pressure generated
inside the jacked kettle is 70psi and preparation of kettle wall is done to prevent
formation of congealed substances. Stabilizer - Bronodiol 1% w/w or Methyl
Paraben 1% w/w or Propyl Paraben 1% w/w may be used to enhance its shelf-life.
6. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
7. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
8. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 3
BATCH SIZE-50 KG
1. MIXING:- 3 kg Povidone-Iodine and 0.55 kg Tinidazole is mixed in a suitable
mixer. The angle of entry of the propeller shaft and the depth of the propeller is
adjusted. A metal spatula is held in position to increase the turbulence to provide
better mixing. 3.70 Kg of Sucralfate is added and mixed. Aeration has been
avoided to provide stable emulsion.
2. HOMOGENIZATION:- The mixing material is homogenized in a suitable
homogenizer to achieve a product of required viscosity at 2000psi.
3. PREPARATION OF OIL PHASES:- Propylene glycol 5 Kg i.e., humactant
and PEG 400 - 25 litres and PEG 4000 - 15 litres are placed in stainless steel
steam jacketed kettle, melted at a temperature 60° C. The oil phase transferred by
gravity to emulsifying mixing kettle.
4. MIXING OF PHASES:- The solid phase and oil phase are mixed at a
temperature of 70° C and this process is done by the use of suitable pump and a
suitable mixer. .
5. COOLING PHASE:- The temperature of the kettle jacket is decreased gradually
at a rate consistent with the mixing of the emulsion and the pressure generated
inside the jacked kettle is 70psi and preparation of kettle wall is done to prevent
formation of congealed substances. Stabilizer - Bronodiol 1% w/w or Methyl
Paraben 1% w/w or Propyl Paraben 1% w/w may be used to enhance its shelf-life.
6. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless '
steel container of suitable size.
7. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
8. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 4
BATCH SIZE-10 KG
1. PART-1:- PEG 400 3 kg is taken and Povidone-Iodine 0.5 kg is added slowly
with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in
PEG 400.
2. PART-2:- PEG 4000 -1.9kg & PEG 400 -2.7 kg are mixed and heated upto 70°C.
The slurry is transferred in a suitable container at 70°C passing through 40 mesh.
3. PART-3:- A slurry of Sucralfate 0.75 kg and PEG 400 -0.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Tinidazole 0.11 kg and PEG 400 -0.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Povidone
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 5
BATCH SIZE-100 KG
1. PART-1:- PEG 400 30 kg is taken and Povidone-Iodine 6 kg is added slowly
with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in
PEG 400.
2. PART-2:- PEG 4000 -19kg & PEG 400 -27 kg are mixed and heated upto 70°C.
The slurry is transferred in a suitable container at 70°C passing through 40 mesh.
3. PART-3:- A slurry of Sucralfate 7.35 kg and PEG 400 -5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Tinidazole 1.05 kg and PEG 400 -5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Povidone
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 6
BATCH SIZE-50 KG
1. PART-1:- PEG 400 15 kg is taken and Povidone-Iodine 3 kg is added slowly
with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in
PEG 400.
2. PART-2:- PEG 4000 -9.5 kg & PEG 400 -13.5 kg are mixed and heated upto
70°C. The slurry is transferred in a suitable container at 70°C passing through 40
mesh.
3. PART-3:- A slurry of Sucralfate 3.70 kg and PEG 400 -2.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Tinidazole 0.55 kg and PEG 400 -2.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Povidone
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 7
BATCH SIZE-10 KG
1. PART-1:- PEG 400 3 kg is taken and Povidone-Iodine 0.5 kg is added slowly
with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in
PEG 400.
2. PART-2:- PEG 4000 -1.9kg & PEG 400 -2.7 kg are mixed and heated upto 70°C.
The slurry is transferred in a suitable container at 70°C passing through 40 mesh.
3. PART-3:- A slurry of Sucralfate 0.75 kg and PEG 400 -0.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Ornidazole 0.11 kg and PEG 400 -0.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Povidone
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

BATCH SIZE-100 KG Example 8
1. PART-1:- PEG 400 30 kg is taken and Povidone-Iodine 6 kg is added slowly
with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in
PEG 400.
2. PART-2:- PEG 4000 -19kg & PEG 400 -27 kg are mixed and heated upto 70°C.
The slurry is transferred in a suitable container at 70°C passing through 40 mesh.
3. PART-3:- A slurry of Sucrose octasulfate 7.35 kg and PEG 400 -5 kg is prepared.
It is passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Tinidazole 1.05 kg and PEG 400 -5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Povidone
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 9
BATCH SIZE-50 KG
1. PART-1:- PEG 400 15 kg is taken and Povidone-Iodine 3 kg is added slowly
with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in
PEG 400.
2. PART-2:- PEG 4000 -9.5 kg & PEG 400 -13.5 kg are mixed and heated upto
70°C. The slurry is transferred in a suitable container at 70°C passing through 40
mesh.
3. PART-3:- A slurry of Sucralfate 3.70 kg and PEG 400 -2.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Ornidazole 0.55 kg and PEG 400 -2.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Povidone
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 10
BATCH SIZE-10 KG
1. PART-1:- PEG 400 3 kg is taken and Cadexomer Iodine 0.56 kg is added slowly
with manual stirring to make a slurry. Cadexomer Iodine is soaked for 6 hours in
PEG 400.
2. PART-2:- PEG 4000 -1.9kg & PEG 400 -2.7 kg are mixed and heated upto 70°C.
The slurry is transferred in a suitable container at 70°C passing through 40 mesh.
3. PART-3:- A slurry of Sucralfate 0.75 kg and PEG 400 -0.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Tinidazole 0.11 kg and PEG 400 -0.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Cadexomer Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Cadexomer
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 11
BATCH SIZE-100 KG
1. PART-1:- PEG 400 30 kg is taken and Cadexomer Iodine 5.56 kg is added
slowly with manual stirring to make a slurry. Cadexomer Iodine is soaked for 6
hours in PEG 400.
2. PART-2:- PEG 4000 -19kg & PEG 400 -27 kg are mixed and heated upto 70°C.
The slurry is transferred in a suitable container at 70°C passing through 40 mesh.
3. PART-3:- A slurry of Sucralfate 7.35 kg and PEG 400 -5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Tinidazole 1.05 kg and PEG 400 -5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Cadexomer Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Cadexomer
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 12
BATCH SIZE-50 KG
1. PART-1:- PEG 400 15 kg is taken and Cadexomer Iodine 3.2 kg is added slowly
with manual stirring to make a slurry. Cadexomer Iodine is soaked for 6 hours in
PEG 400.
2. PART-2:- PEG 4000 -9.5 kg & PEG 400 -13.5 kg are mixed and heated upto
70°C. The slurry is transferred in a suitable container at 70°C passing through 40
mesh.
3. PART-3:- A slurry of Sucralfate 3.70 kg and PEG 400 -2.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Tinidazole 0.55 kg and PEG 400 -2.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Cadexomer Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Cadexomer
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 13
BATCH SIZE-10 KG
1. PART-1:- PEG 400 3 kg is taken and Povidone-Iodine 0.5 kg is added slowly
with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in
PEG 400.
2. PART-2:- PEG 4000 -1.9kg & PEG 400 -2.7 kg are mixed and heated upto 70°C.
The slurry is transferred in a suitable container at 70°C passing through 40 mesh.
3. PART-3:- A slurry of Sucrose octasulfate 0.75 kg and PEG 400 -0.5 kg is
prepared. It is passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Tinidazole 0.11 kg and PEG 400 -0.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Povidone
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 14
BATCH SIZE-100 KG
1. PART-1:- PEG 400 30 kg is taken and Povidone-Iodine 6 kg is added slowly
with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in
PEG 400.
2. PART-2:- PEG 4000 -19kg & PEG 400 -27 kg are mixed and heated upto 70°C.
The slurry is transferred in a suitable container at 70°C passing through 40 mesh.
3. PART-3:- A slurry of Sucrose octasulfate 7.35 kg and PEG 400 -5 kg is prepared.
It is passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Tinidazole 1.05 kg and PEG 400 -5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Povidone
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Example 15
BATCH SIZE-50 KG
1. PART-1:- PEG 400 15 kg is taken and Povidone-Iodine 3 kg is added slowly
with manual stirring to make a slurry. Povidone Iodine is soaked for 6 hours in
PEG 400.
2. PART-2:- PEG 4000 -9.5 kg & PEG 400 -13.5 kg are mixed and heated upto
70°C. The slurry is transferred in a suitable container at 70°C passing through 40
mesh.
3. PART-3:- A slurry of Sucrose octasulfate 3.70 kg and PEG 400 -2.5 kg is
prepared. It is passed through 40 mesh and added to container simultaneously.
4. PART-4:- A slurry of Tinidazole 0.55 kg and PEG 400 -2.5 kg is prepared. It is
passed through 40 mesh and added to container simultaneously.
5. MIXING: The container is being cooled gradually at temperature below 50°C.
At the temperature 45°C, slurry of Povidone Iodine (Part-1) is added to the
container and it is stirred slowly for 3-4 hours with cooling. Thick mass
preparation takes place and it is washed to reduce the concentration of Povidone
Iodine.
6. VACUUM STIRRING:- Stirring is done at vacuum for 10 minutes and vacuum
is released slowly and this process is repeated for 2-3 times.
7. STORAGE OF SEMI-SOLIDS:- The finished phase is stored in a stainless
steel container of suitable size.
8. TRANSFER OF MATERIAL FOR PACKING:- The semi-solid finished
phase is transferred to the filling equipment.
9. FILLING AND SEALING:- The semi-solid material are filled by suitable
ointment filling machine into suitable containers and sealed properly.

Certain test results based on experiments conducted in one of the
leading Medical Colleges in Eastern India clearly establish the unexpectedness/
synergism exhibited by the therapeutic composition of this invention. It will be
clear from the anti-bacterial spectrum of the individual drugs that the composition
of this invention has greater clinical benefits as well as expanded anti-bacterial
activity. Moreover, the subject composition shows anti-inflammatory (by blocking
the inflammatory mediators) as well as regenerative properties (by binding EGF),
and is well-tolerated with no contra- indications or side effects even after prolonged
topical application.
To evaluate the role of the therapeutic composition of the present
invention containing tinidazole, sucralfate and povidone iodine in the healing
process of post surgical and contaminated superficial wounds, studies were
conducted with both indoor and outdoor patients of Department of Surgery at
N.R.S. Medical College & Hospital in Kolkata. Patients receiving systemic (oral or
i.v.) Tinidazole or Ornidazole were excluded from study.
Example 16
30 patients were evaluated with surgical site infections, diabetic ulcers,
ulcers due to peripheral vascular disease and super ficial epithetial breachers by
topical application of the composition of this invention. Another 20 patients with
same condistions were also evaluated with placebo ointments.
All wounds were clinically assessed for general appearance, signs of
infection, degree of exudation, skin maceration, wound size, and local pain. A
culture sensitivity swab was taken before the application of ointment, and 7 and
14 days after the applicant of oinment.
Treatment protocol: Wounds were cleansed with sterile normal saline before
treatment. There were no forceful irrigation techniques and no other cleansing
agents utilized. The same dressing technique was used throughout the study. It
consisted of a non-adherent primary dressing and an absorbent secondary
dressing. Treatment with the subject topical oinment was performed once daily.
RESULTS :Results of the topical application were clinically assessed by general
appearance of the wound, signs of infection, degree of exudation, skin maceration,
wound size, and local pain. Culture swabs were taken from the wound. Out of
the 30 patients, 17 patients showed signs of healthy granulation tissue within
first 7 days, whereas in 9 patients the wounds became clean with diminished
discharge within 14 days. 3 patients showed no improvement within 14 days
and needed further surgical treatment. These 3 patients were suffering from
peripheral vascular disease. 1 patient complain of itching over and around the
wound.
Out of the 20 patients treated with placebo ointment, 8 patients
showed signs of healthy granulation tissue after 7 days, and 13 patients showed
signs of improvements, whereas 7 patients showed no signs of healthy granulation
tissue.

EFFICACY OF FORMULATION IN CONTAMINATED WOUND
MANAGEMENT
CONCLUSIONS:
1. TOPICAL APPLICATION OF FORMULATION CONTAINING TINIDAZOLE,
POVIDONE IODINE AND SUCRALFATE SHOWED A DEFINITE ROLE IN
IMPROVING SUPERFICIAL WOUNDS BY CONTROLLING LOCAL
INFECTIONS & AUGMENTING THE PROCESS OF HEALING.
2. THIS TREATMENT IS COST EFFECTIVE IN LONG TERM MANAGEMENT
OF WOUNDS.
3. EFFECTIVE AS ANTIBIOTIC & TISSUE REGENERATIVE OINTMENT
WITHOUT ANY MAJOR SIDE EFFECTS.
From the foregoing discussions and data given hereinbefore it will
be seen that:
(i) the subject therapeutic composition of this invention is well-tolarated and
the constituents drugs do not interfere with the bio availability of each
other;
(ii) no toxic drug interactions are involved with the constituent components ;
(iii) the composition stimulates wounds healing by activating keratinocytes
and fibroblast functions;
(iv) the synergistic combination of the main ingredients effectively shows anti-
microbial action against all possible aerobic and anaerobic micro-organisms
present in the wounds ;
(v) the regenerative and anti-inflammatory property of sucralfate accentuates
anti-microbial and anti-viral perperties of the other two drugs by
epithelialization and angiogenesis, and
(vi) strengthening of exterior cell surface and connective tissue cell matrix makes
it extremely difficult for bacteria and virus to penetrate and colonise the
cells and the tissue.
While the invention has been described in details and with reference
to specific embodiments thereof, it will be apparent to one skilled in the art that
various changes and modifications can be made therein without deviating or
departing from the spirit and scope of the invention. Thus the disclosure contained
herein includes within its ambit the obvious equivalents and substitutes as well.
Having described the invention in detail with particular reference to
the illustrative examples given abovem it will now be more specifically defined by
means of claims appended hereafter.
I claim :
1. A therapeutic composition suited both for medical and veterinary
applications and capable of facilitating healing of wounds and simultaneously
preventing bacterial, fungal and viral infections comprising -
(i) a sucrose complex like sucralfate/sucrose octa acetate/sucrose octa
sulphate,
(ii) a nitroimidazole derivative like tinidazole or ornidazole and
(iii) a compound providing free iodine such as povidone iodine or cadexomer
iodine, in a suitable non-aqueous base like propylene glycol, 'PEG-400'
and 'PEG-4000' (polyethylene glycols), characterized in that the aforesaid
ingredients are present in the following amounts in the final composition -
(i) sucralfate/sucrose octasulfate/sucrose octaacetate - 7.0-7.5% w/w,
(ii) nitroimidazole derivative like tinidazole/ornidazole - 0.99 - 1.25 % w/w and
(iii) free iodine from Povidone iodine or cadexomer iodine - 5 - 6 % w/w
(providing 0.5 % available iodine)
2. A composition as claimed in Claim 1, wherein the ingredients are present
in suitable non-aqueous/aqueous base like propylene glycol, 'PEG-400',
*PEG-4000' (polyethylene glycols) and water, propylene glycol additionally acting
as a humactant.
3. A composition as claimed in Claims 1 and 2, wherein the composition
includes a stabilizer selected from the group of'Bronodiol', methyl paraben and
propyl paraben, present in an amount not exceeding 1% w/w of the said
composition.
4. A composition as claimed in Claims 1 to 3, wherein there is included
medicaments/compounds which enhance Epidermal Growth Factor (EGF) and
Fibroblast Growth Factor (FGF) for regeneration of damaged tissues, bioflavonoids,
haemostatic agents and plant extracts for promoting better healing of skin ulcers.
5. A therapeutic composition suited both for medical and veterinary
applications and simultaneously preventing bacterial, fungal and viral infections,
substantially as hereinbefore described and illustrated by means of appended
Examples.
6. A process for preparing a therapeutic composition suited both for medical
and veterinary applications and simultaneously preventing bacterial, fungal and
viral infections as claimed in any one of the preceding claims, which comprises -
(i) preparation of solid phase by mixing of predetermined amounts of different
ingredients;
(ii) homogenization of solid phase in a suitable homogenizer;
(iii) preparation of oil phases by heating propylene glycol, PEG-400 and
PEG-4000 in a stainless steel steem jacketed kettle at a temperature
of around 60°C and transferring the oil phase to a mixing kettle ;
(iv) mixing of solid and oil phases at a temperature of around 70°C with the
help of a pump and mixer with addition of stabilizer for enhancement of
shelf life of the composition ;
(v) cooling the mixture by gradually decreasing the temperature of the jacketed
kettle at a rate consisting with the mixing of the emulsion ;
(vi) storage of finished phase is done in a stainless steel container of suitable
size;
(vii) transfer of semi-solid material is done from the container to the ointment
filling machine for being filled in suitable contaners/receptacles/collapsible
tubes followed by proper sealing.
7. A process as claimed in Claim 6, wherein a stabilizer in an amount of
1% w/w of the final composition selected from the group of 'Bromodiol', methyl
paraben or propyl paraben is added to the reaction medium during mixing of
solid and oil phases.
8. A process as claimed in Claims 6 and 7, wherein the ingredients are added/
dispersed in oil phases and any undispersed matter is removed by passing it
through a 40-mesh screen and cooling of the semi-solid product is carried out in
steam jacketed kettle, the walls of which are so designed as to prevent formation
of congealed substances.
9. A process as claimed in Claim 8, wherein preparation oil phase is carried
out by mixing 'PEG-400' and PEG-4000' and heating the mixture to a temperature
of 70°C, transferring the mass to a container at 70°C through 40 mesh screen,
preparing slurrys of ingredients separetely in 'PEG-400', cooling the container to
around 40°C while mixing them under stirring and washing the resulting thick
mass to remove excess iodine, stirring the semi-solid mass under vacuum and
thereafter releasing vacuum, followed by storage
and transfer of finished product for silling into containers, sealing and packing
or for packing into bulk containers.
10. A process for preparing a therapeutic composition suited both for medical
and veterinary applications and simultaneously preventing bacterial, fungal and
viral infections, substantially as hereinbefore described and illustrated in the
Examples given hereinbefore.

1. A therapeutic composition suited both for medical and veterinary
applications and capable of facilitating healing of wounds and simultaneously
preventing bacterial, fungal and viral infections comprising -
(i) a sucrose complex like sucralfate/sucrose octa acetate/sucrose octa
sulphate,
(ii) a nitroimidazole derivative like tinidazole or ornidazole and
(iii) a compound providing free iodine such as povidone iodine or cadexomer
iodine, in a suitable non-aqueous base like propylene glycol, 'PEG-400'
and 'PEG-4000' (polyethylene glycols), characterized in that the aforesaid
ingredients are present in the following amounts in the final composition -
(i) sucralfate/sucrose octasulfate/sucrose octaacetate - 7.0-7.5% w/w,
(ii) nitroimidazole derivative like tinidazole/ornidazole - 0.99 - 1.25 % w/w and
(iii) free iodine from Povidone iodine or cadexomer iodine - 5 - 6 % w/w
(providing 0.5 % available iodine)

Documents:

283-KOL-2010-(08-09-2014)-FORM-13.pdf

283-KOL-2010-(14-07-2014)-CLAIMS.pdf

283-KOL-2010-(14-07-2014)-CORRESPONDENCE.pdf

283-KOL-2010-(14-07-2014)-DESCRIPTION (COMPLETE).pdf

283-KOL-2010-(14-07-2014)-FORM-3.pdf

283-KOL-2010-(14-07-2014)-PETITION UNDER RULE 137.pdf

283-KOL-2010-(17-05-2013)-CORRESPONDENCE.pdf

283-KOL-2010-(17-11-2014)-FORM-13.pdf

283-KOL-2010-(23-03-2012)-CORRESPONDENCE.pdf

283-kol-2010-abstract.pdf

283-KOL-2010-CANCELLED PAGES.pdf

283-kol-2010-claims.pdf

283-kol-2010-correspondence.pdf

283-kol-2010-description (complete).pdf

283-KOL-2010-EXAMINATION REPORT.pdf

283-kol-2010-form 1.pdf

283-KOL-2010-FORM 13.pdf

283-KOL-2010-FORM 18.pdf

283-kol-2010-form 2.pdf

283-kol-2010-form 5.pdf

283-KOL-2010-FORM 9.pdf

283-KOL-2010-GRANTED-ABSTRACT.pdf

283-KOL-2010-GRANTED-CLAIMS.pdf

283-KOL-2010-GRANTED-DESCRIPTION (COMPLETE).pdf

283-KOL-2010-GRANTED-FORM 1.pdf

283-KOL-2010-GRANTED-FORM 2.pdf

283-KOL-2010-GRANTED-FORM 3.pdf

283-KOL-2010-GRANTED-FORM 5.pdf

283-KOL-2010-GRANTED-SPECIFICATION-COMPLETE.pdf

283-kol-2010-pa.pdf

283-KOL-2010-PETITION UNDER RULE 137.pdf

283-KOL-2010-REPLY TO EXAMINATION REPORT.pdf

283-kol-2010-specification.pdf

721-KOLNP-2007-KOL-(11-12-2013)-FORM-13.pdf

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Patent Number

264243

Indian Patent Application Number

283/KOL/2010

PG Journal Number

51/2014

Publication Date

19-Dec-2014

Grant Date

16-Dec-2014

Date of Filing

22-Mar-2010

Name of Patentee

SHOMENATH ROY CHOWDHURY

Applicant Address

46/31/1, GARIAHAT ROAD, BALLYGUNGE NEW A.C. MARKET, 5TH FLOOR, KOLKATA - 700029, WEST BENGAL, INDIA

Inventors:

#	Inventor's Name	Inventor's Address
1	SHOMENATH ROY CHOWDHURY	46/31/1, GARIAHAT ROAD, BALLYGUNGE NEW A.C. MARKET, 5TH FLOOR, KOLKATA - 700029, WEST BENGAL, INDIA

PCT International Classification Number

A61K31/00

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA