Title of Invention

DERMATOLOGICAL PRODUCT AND A PROCESS FOR MANUFACTURING THE SAID DERMATOLOGICAL PRODUCT

Abstract

ABSTRACT Dermatological product and a process for manufacturing the said dermatological product (843/MAS/1999) The invention relates to dermatological product and a process for manufacturing said dermatological product comprising the following steps; Dispersing Miconazole nitrate in Propylene Glycol to a solution of liquid Paraffin, Cetosterayl Alcohol, White soft Paraffin (White Petrolatum), Cetomacragol 1000 (Polyoxyl 20 Cetosteryl Ether) and Poly ethylene Glycol - 400 ( Macrogol-400) with continuous stirring; Mixing the above dispersion to a aqueous solution of Bronopol and Zinc Sulphate; Cooling the above mixture to 55 deg C; Adding solutions of Chlorocresol in Propylene Glycol; Clobetasol Propionate in Benzyl Alcohol; Propylene Glycol; Gentamicin Sulphate in water to the above mixture to form cream; Homogenizing the above cream at room temperature with continuous stirring for half an hour.

Full Text

'Preamble to the Description The invention is directed to the dermatological product and a process for manufacturing the dermatological product, in general and as such this invention is in the field of pharmaceutical industry. This invention pertains further to introduction of Zinc as one component in the manufacture of Dermatological product for protecting human skin. It is well known in the art that Zinc containing compounds are of great benefit to humans. Some of them are well known antimicrobials. Zinc is an essential component of several metalloenzymes and is an essential nutrient and constituent of all biological systems. Currently Zinc is known to be required by approximately 200 metalloenzymes in the human body. Zinc concentrations tend to be higher in the skin and in human skin six times more Zinc is found in the superficial / top skin layer. The importance of Zinc in the growth and maintenance of the functional integrity of the skin is unequivocal. Response of the top layer of the skin to Zinc is indicated by skin growth, return of skin colour and prevention of hair falling due to ageing. The path physiological role of Zinc in human being has been proved through animal studies which proves the effect of Zinc in the treatment of lesion, varicose ulcer and other forms of injuries and in the repair of skin. In view of extensive studies in the utilization of Zinc in dermatological composition for protection of human skin, research and development has been exclusively focused on the use of Zinc in this area of interest. Considerable clinical interest and commercial value has been attached to the premise that Zinc accelerates the healing of wounds clearly. If Zinc is beneficial to wound healing in the skin one would expect it to promote cell proliferation, migration and differentiation in regenerating tissues because of its antibacterial and non allergic properties. As an accepted practice Zinc is used in many of the world's finest cosmetic products. -1 OBJECTIVE OF THIS INVENTION > A general objective of this invention is to provide a new product of corticosteroid with Zinc Sulphate that provides the desired therapeutic response through topical administration in the form of cream. > The invention relates to a dermatological product, which provides usage for bacterial infection, fungal infection, and anti-inflammatory and dermatological disorders such as psoriasis, wound healing and eczema. > This dermatological product is unique in that it contains Zinc as an active ingredient. ADVANTAGES The various benefits of the topical zinc is enumerated as under: Topical Zinc augments cutaneous immune response. Topical Zinc heals genital lesions. Topical Zinc is a mitotic agent for epidermal cells. Topical Zinc tackles higher levels of skin infections also. Topical Zinc is a photo protector. Topical Zinc treats acne vulgaris. Topical Zinc protects herpes simplex. Topical Zinc is a painless debriding agent. Topical Zinc exhibits enhanced percutaneous absorption and cutaneous bioavailability. Topical Zinc helps in isochoric dermatitis. Topical Zinc accelerates wound healing. Topical Zinc exhibits better aqueous solubility. Topical Zinc increases skin permeability. Topical Zinc is useful in the treatment of folliculate reticulate, pappilomatosis and psoriasis. Topical Zinc resolves erosive diaper rash. Thus Zinc unquestionably is superior and effective for topical therapy. UNIQUENESS OF THIS DERMATOLOGICAL PRODUCT The existing skin ointments / creams available in the market contain STEROIDS / ANTIBACTERIAL Drugs / ANTI FUNGAL Drugs either alone or in a combination but not with Zinc Sulphate. Till this date there is no dermatological preparation in nature as this invented Dermatological product which provides all the benefits of steroid, anti bacterial and anti¬fungal drugs along with the excellent benefits of Zinc as mentioned earlier. This is the salient feature of this invention. As such Dermatological product is a unique combination of its kind. RATIONALE OF ZINC IN DERMATOLOGICAL PRODUCT Dermatological conditions are often caused by allergy accompanied by inflammation, irritation and itching. They are further complicated by either bacterial infection or fungal infection or both. Any dermatological drug combination should be able to control allergy, inflammation and also bacterial or fungal infection and wound healing. It is therefore evident that the invented Dermatological product is versatile in its scope and application. The dermatological product consists of the following ingredients:- 1. Clobetasol Propionate: A powerful steroid used in dermatological conditions to prevent allergy and control infl£immation and itching. 2. Gentamicin: Antibiotic to control bacterial infections of skin. 3. Miconazole Miconazole is a drug for the treatment of fungal complications of the skin. 4. Zinc is used to assist in rapid wound healing and to provide all its benefits in dermatological conditions. It is the primary object of the invention to invent a novel dermatological product namely ZINCODERM-GM ' It is another objective of the invention to invent a novel dermatological product using Zinc as one of the ingredients. It is another object of the invention to invent a safe and useful drug for combating skin diseases. Further objects of the invention will be clear from the following description:- 1.0 Process The process involves; ♦ selection of active ingredients in particular quantity to achieve the medicinal activity of the product, * selection of specific solvent for the active ingredients. There are thousands of solvents available, but here solvents has been chosen based on the medicinal activity in such a way that should not be harmful and without side effect, ♦ selecting the sequence of process steps in order to achieve the desired product possessing medicinal activity, ♦ heating the mixture to an optimum temperature in such a way that the solvents should not undergo evaporation completely, stirring and cooling in order to obtain the desired product possessing medicinal activity the selection of optimum temperature is playing important role. novelty and inventiveness. The comparative activity study has been given in the description and ♦ the process results in a formation of adduct by the reaction between the reactants used and the product of the current invention has synergistic effect, clinical activity proof of which has been given in the description by way of graphical representation i.e. efficacy of the product. Statement of invention: A process for manufacturing dermatological product comprising the following steps; Dispersing Miconazole nitrate in Propylene Glycol to a solution of liquid Paraffin, Cetosterayl Alcohol, White soft Paraffin (White Petrolatum), Cetomacragol 1000 (Polyoxyl 20 Cetosteryl Ether) and Poly ethylene Glycol - 400 ( Macrogol- 400) with continuous stirring; Mixing the above dispersion to a aqueous solution of Bronopol and Zinc Sulphate under vacuum; Cooling the above mixture to 55 deg C; Adding solutions of Chlorocresol in Propylene Glycol; Clobetasol Propionate in Benzyl Alcohol and Propylene Glycol; Gentamicin Sulphate in water to the above mixture to form cream; Homogenizing the above cream at room temperature with continuous stirring for half an hour. A detailed step by step process for manufacturing dermatological product comprising the following steps: a) Take purified water in a vessel and add Bronopol and Zinc Sulphate into the vessel while stirring to dissolve. Heat the content to 75°C with continuous stirring. b) Take liquid Paraffin, Cetosterayl Alcohol, White soft Paraffin (White Petrolatum), Cetomacragol 1000 (Polyoxyl 20 Cetosteryl Ether) and Poly ethylene Glycol - 400 ( Macrogol-400) in the vessel and mix well. Heat the contents to 75°C with continuous stirring. c) Disperse Miconazole nitrate in Propylene Glycol in a stainless steel vessel and pass the above dispersion through colloid mill. Transfer the dispersion to the content of step (b) under continuous stirring. d) Transfer the contents of step (b) to the contents of step (a) under vacuum with continuous stirring in a separate mixing tank e) Cool the contents of step (d) to 55°C with continuous stirring. f) Dissolve Chlorocresol in Propylene Glycol in a stainless steel vessel and transfer the contents to step (e) with continuous stirring. g) Dissolve Clobctasol Propionate in Benzyl Alcohol in a stainless steel vessel and add Propylene glycol mix well and transfer the solution to the contents to step (e) with continuous stirring. h) Dissolve Gentamicin Sulphate in purified water in a stainless steel vessel and transfer the solution to the contents to step (e) with continuous stirring i) Cool the resultant cream to room temperature under continuous stirring and homogenize for half an hour. pH of 10% dispersion of the cream in water is between 3.3 to 4.0 Batch formula for the preparation of 350 Kg Dermatological product 2.0 MANUFACTURING PROCESS OF DERMATOLOGICAL PRODUCT - EXAMPLE 2.1 Check the weight of all ingredients before addition. 2.2 Transfer 185.000 kg of Purified Water by passing through nylon cloth (200#) into the water phase vessel and heat the content to 72°C ± 2°C with continuous stirring. 2.3 ' Transfer 1.000 kg of Purified Water into a suitable Stainless Steel Vessel and dissolve 0.034 kg of Bronopol. Transfer the solution to the content of Step (2.2) under stirring by passing through nylon cloth (200#). Transfer 11.000 kg of Purified Water into a suitable Stainless Steel vessel and dissolve 9.625 kg of Zinc Sulphate hepta hydrate. Transfer the solution to the contents of Step (2.2) under stirring, by passing through nylon cloth (200#) 2.4 Transfer 17.500 kg of Light Liquid Paraffin, 26.300 kg of Cetostearyl Alcohol, 20.350 kg of White Soft Paraffin (White Petrolatum), 7.900 kg of Cetomacrogol 1000 (Polyoxyl 20 Cetostearyl Ether) and 17.500 kg of Poly ethylene glycol 400 ( Macrogol-400) into the oil phase vessel and heat the contents to 75°C . Stir and mix well. 2.5 Disperse 7.700 kg of Miconazole Nitrate in 28.200 kg of Propylene Glycol in a suitable Stainless Steel vessel, pass the above dispersion through Colloid Mill and transfer it to the contents of Step(2.4) under stirring. 2.6 Transfer the water phase contents of Step (2.2) and the oil phase contents of Step (2.4) into the mixing vessel by applying vacuum and mix well (fast speed) at 78°C ± 2°C. (maintain vacuum at 700-400 mm Hg) and 2.7 Then cool the above contents to 55°C with continuous stirring (fast speed), by circulating tower water through the jacket of the mixing vessel. 2.8 Dissolve 0.350 kg of Chlorocresol in 3.400 kg of Propylene Glycol in a suitable Stainless Steel Vessel. Filter the solution through nylon cloth (200#) into the contents of Step (2.7) under stirring (slow speed). Cool the contents to 45°C with continuous stirring (slow speed), by circulating tower water through the jacket of the mixing vessel. 2.9 Dissolve 0.193 kg of Clobetasol Propionate in 2.000 Itr of Benzyl Alcohol in a suitable Stainless Steel Vessel. Add 3.400 kg of Propylene Glycol to it and mix well. Transfer the solution through nylon cloth (200#) to the contents of Step (2.7) under stirring (slow speed). Rinse the Stainless Steel Vessel with 0.500 Itr ■ of Benzyl Alcohol and transfer into the mixing vessel. Cool the contents to 40°C with continuous stirring (slow speed), by circulating tower water through the jacket of the mixing vessel. 2.10 Dissolve 0.850 kg of Gentamicin Sulphate in 11.000 kg of Purified Water in a suitable Stainless Steel Vessel. Transfer the solution through nylon cloth (200#) to the contents of Step (2.7) under stirring (slow speed). 2.11 Cool the cream to 35-37°C, while continuing stirring (fast speed) & homogenizing (fast speed) for1/2Hr. Check and record the pH of 10% dispersion . in water (Limit: 3.3 to 4.0). 2.4 Clinical trial report on topical Zinc with steroid A double-blind randomized multicentric controlled study of topical 0.05 % Clobetasol propionate with 2.5 % Zinc Sulphate preparation was conducted. Report Therapeutic responses were significantly high in the study among the patients who underwent treatment with 0.05% Clobetasol Propionate with 2.5 % Zinc combination as compared to plain 0.05 % Clobetasol Propionate cream. Addition of topical Zinc auguments the efficacy of Clobetasol Propionate in the treatment of psoriasis, eczema and lichenplanus Brief description of the drawing: Figure -1 shows the schematic diagram of dermatological formulation process. Figure - 2 shows the graphical expression - % of complete recovery from symptoms. This proves the synergistic effect and efficacy of the invented product. We claim 1) A process for manufacturing dermatological product comprising the following steps; Dispersing Miconazole nitrate in Propylene Glycol to a solution of liquid Paraffin, Cetosterayl Alcohol, White soft Paraffin (White Petrolatum), Cetomacragol 1000 (Polyoxyl 20 Cetosteryl Ether) and Poly ethylene Glycol - 400 (Macrogol-400) with continuous stirring; Mixing the above dispersion to a aqueous solution of Bronopol and Zinc Sulphate under vacuum; Cooling the above mixture to 55 deg C; Adding solutions of Chlorocresol in Propylene Glycol; Clobetasol Propionate in Benzyl Alcohol and Propylene Glycol; Gentamicin Sulphate in water to the above mixture to form cream; Homogenizing the above cream at room temperature with continuous stirring for half an hour. 2) The process as claimed in claim 1 wherein the batch formula for the dermatological product is as follows, 0.193 Kg of Clobetasol Propionate USPgrade; 26.3 Kg of Cetostearyl Alcohol IP grade; 7.9 Kg of Cetomacrogol 1000 (Polyoxyl 20 Cetostearyl Ether) USP grade; 17.5 Kg of Light Liquid Paraffin IP grade; 20.35 Kg of White Soft Paraffin (White Petrolatum) IP grade; 35 Kg of Propylene Glycol IP grade; 2.5 Ltr of Benzyl Alcohol BP grade; 0.35 Kg of Chlorocresol IP grade; 0.034 Kg of Bronopol BP grade; 9.625 Kg of Zinc Sulphate hepta hydrate IP grade; 0.85 Kg of Gentamicin Sulphate IP grade; 7.7 Kg of Miconazole Nitrate IP grade; 17.5 Kg of Polyethylene gIycol-400 (Macrogol - 400) USP grade; 208 Kg of Purified Water IP grade 3) The process as claimed in claim 1 wherein 1.12% additional purified water is added to compensate evaporation loss during processing. 4) The process as claimed in claim 1 wherein the dispersion of the Miconazole nitrate in Propylene Glycol is carried out in a colloid mill. 5) The process as claimed in claim 1 wherein dispersing and mixing steps are carried out in a Stainless Steel vessel with continuous stirring and heating to a temperature of 75 deg C. 6) The process as claimed in claim 1 wherein comprises Clobetasol Propionate is USP grade and its ratio is 0.05 %w/w, Miconazole Nitrate is IP grade and its ratio is 2.0 % w/w. Zinc Sulphate is IP grade and its ratio is 2.5 %w/w and Gentamicin Sulphate is IP grade and its ratio is 0.10 %w/w 7) The process as claimed in claim 1 wherein the batch size can be varied according to the proportion of the reactants used. 8) The process as claimed in claim 1 wherein the final dermatological product is a cream. 9) The process as claimed in claim 1 wherein the process comprises filling the final product in collapsible Aluminium tubes in required quantities using double head rotary tube filling machine 10) Cream of dermatological product whenever prepared by the above said processes. 11) The cream as claimed in claim 10 wherein pH of 10% dispersion of the cream in water is between 3.3 to 4.0 12) A process for manufacturing dermatological product substantially as herein described.

Documents:

0843-mas-1999 abstract.pdf

0843-mas-1999 claims.pdf

0843-mas-1999 description(complete).pdf

0843-mas-1999 drawings.pdf

0843-mas-1999 abstract-duplicate.pdf

0843-mas-1999 claims-duplicate.pdf

0843-mas-1999 correspondence-others.pdf

0843-mas-1999 correspondence-po.pdf

0843-mas-1999 description(complete)-duplicate.pdf

0843-mas-1999 drawings-duplicate.pdf

0843-mas-1999 form-1.pdf

0843-mas-1999 form-18.pdf

0843-mas-1999 form-26.pdf