A novel synergistic pharmaceutical composition for topical applications

Medicilon has extensive experience of performing stability studies on active pharmaceutical ingredients, early prototype formulations and finished dosage forms. Stability testing is performed according to FDA-ICH guidelines, client approved protocols and standard operating procedures. Email:marketing@medicilon.com.cn web:www.medicilon.com

A novel synergistic pharmaceutical composition for preparation of topical formulations for prophylaxis and treatment of wounds, burn wounds, skin grafts, pressure ulcers and diabetic foot ulcers is disclosed. The synergistic composition comprises a mitogenic protein in combination with one or more bactericidal and bacteriostatic agents. The mitogenic protein in the invention is Recombinant Human Epidermal Growth Factor (rh-EGF of Bharat Biotech International Limited) and /or any other growth factor like rh-PDGF-BB and the bactericidal and bacteriostatic agents are broad spectrum antibiotics silver sulfadiazine (SSD) and chlorhexidine glucomate (CHG). The topical formulations, in addition to the synergistic composition, also comprise base ingredients, carriers, preservatives, emulsifiers, skin. emollients and soothers and one or more other constituents. The novel composition results in synergistic effects like broader antibacterial coverage, reversal of silver effect of SSD by rh-EGF, effectiveness against silver resistant microorganisms in burn wounds, and better and faster wound healing. The novel composition may be used to prepare the topical formulations in the form of cream, gel or liquid. The novel formulations have longer shelf life and are stable for more than two years at the storage temperature of 2-8° degrees.

FIELD OF THE INVENTION: The invention relates to a novel synergistic pharmaceutical composition for topical applications. More particularly, the invention relates to a novel synergistic pharmaceutical composition for the preparation of topical formulations for use in prophylaxis and treatment of wounds, burn wounds, skin grafts, pressure ulcers, diabetic foot ulcers and other skin diseases. The novel formulation of the invention comprises one or more synergistically active ingredients and one or more inactive ingredients. The synergistically active ingredients comprise a mitogenic protein (growth factor) in synergistic combination with one or more bactericidal and bacteriostatic agents. More particularly, the synergistically active ingredients comprise Recombinant Human Epidermal Growth Factor (rh-EGF) (REGEN-D™ of Bharat Biotech International Limited) and or Platelet Derived Growth Factor (rh-PDGF-BB), silver sulfadiazine (SSD) and chlorhexidine gluconate (CHG) whereas, one or more inactive ingredients may comprise carriers, preservatives, emulsifiers, skin emollients and soothers and one or more other constituents. The novel composition of the invention may be used for the preparation of topical formulations for application on wounds, burn wounds, skin grafts, pressure ulcers, diabetic foot ulcers and other skin diseases either in the form of a cream or gel or liquid form.

A novel synergistic broad spectrum pharmaceutical composition for preparation of topical formulations for prophylaxis and treatment of wounds, burn wounds, skin grafts, pressure ulcers, diabetic foot ulcers and other skin diseases is disclosed, wherein the formulation may be in the form of cream, gel or liquid.

The novel synergistic composition of the invention comprises at least three synergistically active ingredients and one or more inactive ingredients. The synergistically active ingredients comprise one or more broad spectrum bactericidal agent, one or more broad spectrum bacteriostatic agent and a mitogenic growth factor.

The inactive ingredients are used to provide a base, permeability and stability to the formulation and comprise carriers, preservatives, emulsifiers, skin emollients and soothers and one or more other constituents.

The bactericidal and bacteriostatic agents are selected from the group consisting of bacitracin, silver sulfadiazine (SSD), nitrofurazone, chlorhexidine gluconate (CHG), polymyxine B sulphate, neomycine, povidone-iodine, mafenide, nitrofurazone and gentamicin. In the preferred embodiment of the invention the broad spectrum bactericidal agent is silver sulfadiazine (SSD) and broad spectrum bacteriostatic agent is chlorhexidine gluconate (CHG). The synergistically inactive ingredients of the formulation are selected from the group consisting of PEG-30 dipolyhydroxystearate, isohexadecane, C-12-15 alkyl benzoate, titanium dioxide, polyhydroxystearic acid, aluminium stearate, alumina, magnesium sulphate, stearic acid, sorbitol, methylparaben sodium, propylparaben sodium, sodium hydroxide, disodium EDTA, ammonium acryloyldimethyltaurate/VP copolymer, dipalmitoyl hydroxyproline, Bois II™, cetyl alcohol, CI 2-15 alkyl benzoate, caprylic/capric triclyceride, tocopheryl acetate, polyacrylamide, C13-14 isoparaffin, ethoxydiglycol, phenoxyethanol, methyl, butyl, ethyl & propylparaben, triethanolamine, light liquid paraffin, pemulen TR-1, carbopol ultrez, mannitol, and Purified water.

The novel synergistic composition of the invention has synergistic effects like broader antimicrobial and I or antibacterial spectrum, effectiveness against SSD resistant microorganisms, better and faster wound healing, reversal of the SSD cytotoxicity, longer stability and shelf life of the formulation with sustained antibacterial / antimicrobial activities.

Various trials and test results have shown that this composition is best suitable for different degrees of burn wounds and this novel synergistic composition can also be used for other indications like wounds, skin grafts, pressure ulcers and diabetic foot ulcers.

Results from the studies clearly indicated that the novel formulation was very effective in different degrees of burns and also for quick healing of the burns without any infection. Stability studies were conducted for these novel formulations, both real time and accelerated time stability studies of this novel formulation have shown that the combination was stable and more efficacious in quick healing of burn wound without any infection.

The novel synergistic composition of the formulation comprising rh-EGF, silver sulfadiazine (SSD) and chlorhexidine gluconate (CHG) prevents the effect of micro-organisms resistant to silver and helps in the permeability of silver in' burn wounds. The CHG even in low concentrations in the formulation helps in permeability of silver in burn wounds thereby enhances the effectiveness of silver against the resistant micro-organisms.

The rationale of the choice of this synergistic combination of rh-EGF of BBIL, SSD and CHG was that sulphonamide resistance is frequently due to a permeability barrier and chlorhexidine is well known to be able to affect this barrier, secondly the combination has prophylactic properties in burn therapy comparable with those of SSD and resistance does not emerge to either of the former and the wound healing process is faster with the three agents of the formulation than the rh-EGF+SSD alone.