WO2013033797A1 - Pharmaceutical composition for treatment of burns and injuries of the skin and its preparation process - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for the treatment of burns, bedsores, varicose ulcers and other skin lesions, consisting essentially the novelty of the combination of sodium salicylate and zinc salts, among these, preferably, zinc sulfate, at specific concentrations, and be even associated to silver sulfafdiazine, being the base of the cream constituted by cetostearyl alcohol, cetostearyl ethoxylated alcohol 20 e o; lanoline, propylenoglycol, paraffine, solid vaseline, of mineral oil, methylparaben and propylparaben. The invention also relates to the process for obtaining the composition.

Description

Description Report of Invention Patent

"PHARMACEUTICAL COMPOSITION FOR TREATMENT OF BURNS AND INJURIES OF THE SKIN AND ITS PREPARATION PROCESS."

FIELD OF THE INVENTION

The present invention relates to a pharmaceutical composition in the form of stable creams containing zinc sulphate salts and sodium salicylate for the treatment of various skin lesions caused by burns, eschar (bedsore) , pyoderma, herpes zoster, and varicose ulcers, and may associated with silver sulfadiazine.

PREVIOUS TECHNIQUE

The early excision technique and grafting have been largely used, targeting the early closure of the wound, thus avoiding complications liable to occur with the open wound. However, the conventional treatment and excision are equally safe and effective in burns involving less than 30% of body surface.

During the evolution of this type of burn, there is always the risk of local and systemic infection, since the environment of this wound can favor the proliferation of microorganisms present therein and need, therefore, drugs for efficient local treatment. Due to tissue ischemia, oral antibiotics administered systematically do not reach the wound efficiently, where they are mostly needed. Therefore topical antibiotic therapy is necessary for direct action on the wound.

There are several topical agents being used for the treatment of burn infections, the most common of which is topical silver sulfadiazine therapy. Such a substance combines antibacterial properties of silver ion and sulfadiazine. It has broad activity spectrum on positive and negative Gram, being particularly effective for Pseudomonas aeruginosa, having also antiviral activity (against herpes zoster) and antifungal activity. The mechanism of the antimicrobial action of silver sulfadiazine may be explained by the reaction of silver ion with the DNA of the bacteria, specifically acting in the replication process. Some studies suggest an interaction of the drug with the bacterial cell wall, making it labile. Its action is prolonged, because it is a complex that dissociates very slowly, resulting in a reservoir of silver at the wound site. It is used in connection with creams or ointments at a concentration of 1%. It should not be associated with the concomitant use of proteolytic enzymes of topical use, because there is the possibility of enzyme inactivation by silver.

OBJECTIVES AND ADVANTAGES OF THE INVENTION

The present invention aims to provide a pharmaceutical composition for the topical treatment of burns that reduces the time for complete release of eschar (bedsore) and contraction and complete epithelization of the wound, and hence substantially reduce the cost of treatment and patient's suffering.

This objective is achieved by employing specific concentrations of sodium salicylate and zinc salts, among these, preferably zinc sulphate.

This composition has the following presentation: zinc sulphate heptahydrate cream at 1% and sodium salicylate at concentrations of 10, 20 and 40%.

The objectives of the invention are also achieved by a second embodiment that has the following formulation: cream of zinc sulphate heptahydrated at 1% and silver sulfadiazine at 1%.

The composition may also be presented in the following ways: cream of sodium salicylate at concentrations of 10, 20 and 40% and silver sulfadiazine at 1%; cream sodium salicylate at concentrations of 10, 20 and 40%. The creams of the present invention are mainly based on the following formulation:

It. was demonstrated by the comparative attached study developed by Dr. Nelson Sarto Piccolo, a national reference in the treatment of burns, the feasibility and advantages of the association object of the present invention. Burns treated with the preferred embodiment of. the present invention - through the combination of sodium salicylate and zinc salts - obtained average release time of eschar below that consumed by other substances, reducing by 50% the period when compared to other existing topical agents in the status of the technique. The time of wound healing obtained a reduction of up to 30% with the use of sodium salicylate and zinc sulfate.

The objectives of the invention are also achieved by a process for the preparation of the creams comprising the following steps:

- Weigh 30% of the cream base and 0.5 of cetostearyl alcohol, 0.2% of methylparaben and 0.15% of propylparaben and melt in a double boiler;

- Weigh the deionized water and heat to 60°C;

- Weigh zinc sulfate and dissolve it in a small part of hot water;

Weigh the sodium salicylate at the desired concentration and dissolve it in the remaining hot water;

- Add 4 into 1, with constant stirring; - Add 3 into 5, stirring until consistency;

- Fill.

In the second embodiment of the invention, the process as shown below:

- Weigh 20% of the cream base described in the table, add conservatives methylparaben at 0.2% and propylparaben at 0.15% and melt in a double boiler;

- Weigh deionized water and heat to 60°C, separating a small part for dissolution of salts of active ingredients;

- Weigh silver sulfadiazine at 1% and make it soluble in water;

- Blend 1, 2 and 3;

- Weigh zinc sulphate (if monohydrated, use at 0.06%; if heptahydrate, use at 1%) and dissolve it in water;

- Add 5 and mix until consistency;

- Fill.

Or in another embodiment of the invention:

- Weigh 30% of the cream base and 0.5 of cetostearyl alcohol, 0.2% of methylparaben and 0.15% of propylparaben.

Melt in a double boiler.

- Weigh deionized water and heat to 60°C, separate a small portion for dissolution of silver sulfadiazine;

- Weigh silver sulfadiazine at 1% and dissolve it in water;

Weigh the sodium salicylate at the desired concentration and add it across the warm water, stirring until complete dissolution of the salt;

- Add 1 into 4;

- Add 3 into 5 and mix until consistency;

- Fill.

Stability tests were performed with up to five years of the formulations left at normal room temperature in cold and hot climates and the conclusion is that medicines containing silver sulfadiazine salts and zinc sulphate are highly stable, remaining unchanged to date. The creams containing salts of sodium salicylate, being at high concentrations, are more susceptible to. changes in stability such as oxidation, but were stable for up to two years or more in the tests to which they were subjected. Microbiological analyzes were performed on random samples and showed no growth of microorganisms.

Claims

1. A pharmaceutical composition CHARACTERIZED by a zinc sulphate heptahydrate cream at 1% and sodium salicylate at concentrations of 10, 20 and 40%.

2. A pharmaceutical composition CHARACTERIZED by a zinc sulphate heptahydrate cream at 1% and silver sulfadiazine at 1%.

3. A pharmaceutical composition CHARACTERIZED by a zinc sulphate heptahydrate cream at the concentrations of 10, 20 and 40% and silver sulfadiazine at 1%.

4. A pharmaceutical composition CHARACTERIZED by a zinc sulphate heptahydrate cream at the concentrations of 10, 20 and 40%.

5. A pharmaceutical composition according to claims 1, 2, 3 and 4, CHARACTERIZED by the cream base constituted by 3.0 kg cetostearyl alcohol, 0.70 kg of cetostearyl alcohol ethoxylated 20 eo; 0.50 g lanolin; 0.10 kg propylenoglycol; 0.70 kg paraffin; 0.70 kg solid Vaseline; 4.3 g mineral oil; 20g methylparaben; 15g propylparaben, for an amount of 10kg.

6. A process for preparing a pharmaceutical composition as defined in claims 1 and 5, CHARACTERIZED as it involves the following steps:

- Weigh 30% of the cream base and 0.5 of cetostearyl alcohol, 0.2% of methylparaben and 0.2T of propylparaben and melt in a double boiler;

- Weigh the deionized water and heat to 60°C;

- Weigh zinc sulphate and dissolve it in a small part of the hot water;

- Weigh the sodium salicylate at the desired concentration and dissolve it in the remaining hot water;

- Add 4 into 1, with constant stirring;

- Add 3 into 5, stirring until consistency;

- Fill.

7. A process for preparing a pharmaceutical composition as defined in claims 2 and 5, CHARACTERIZED because it involves the following steps:

- Weigh 20% of the cream base, add conservatives methylparaben at 0.2% and propylparaben at 0.15T and melt in a double boiler;

- Weigh deionized water and heat to 60°C, separating a small part for dissolution of salts of active ingredients;

- Weigh silver sulfadiazine at 1% and make it soluble in water;

- Blend 1, 2 and 3;

Weigh the zinc sulphate (if monohydrated, use 0.06%; if heptahydrate, use 1%) and dissolve it in water, - Add 5 and mix until consistency;

- Fill.

8. A process for preparing a pharmaceutical composition as defined in claims 3 and 5, CHARACTERIZED because it involves the following steps:

- Weigh 30% of the cream base and 0.5 of cetostearyl alcohol, 0.2% of methylparaben and 0.15% of propylparaben, Melt in a double boiler.

- Weigh deionized water and heat to 60°C, separate a small portion for dissolution of silver sulfadiazine;

- Weigh silver sulfadiazine at 1% and dissolve it in water;

Weigh the sodium salicylate at the desired concentration and add it across the warm water, stirring until complete dissolution of the salt;

- Add 1 into 4;

- Add 3 into 5 and mix until consistency;

- Fill.