Carbamide peroxide compositions for the treatment of...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...

Reexamination Certificate

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C514S714000

Reexamination Certificate

active

06573301

ABSTRACT:

FIELD OF THE INVENTION
This present disclosure relates to compositions containing carbamide peroxide and urea as components for the treatment of dermatological disorders.
BACKGROUND OF THE INVENTION
There is a need to provide carbamide peroxide compositions, which are easily and economically prepared, which have a smooth texture appropriate for cosmetic products, and which are enhanced by exhibiting greater keratolytic and antibacterial effects. Compositions having carbamide peroxide and urea as components might satisfy such a need because urea has keratolytic activity and has the property of denaturing and solubilizing proteins in addition to antimicrobial activity. However, urea containing formulations generally tend to be neutral to slightly alkaline, while carbamide peroxide formulations are generally most stable under acidic conditions.
SUMMARY
The present invention relates to a topical composition that combines the benefits of urea and carbamide peroxide and yet achieves a stable formulation. In one embodiment the topical composition comprises carbamide peroxide, urea, and a dermatologically acceptable carrier, wherein the composition has a pH between about 2.5 and about 9. In another embodiment the topical composition comprises about 0.5 to about 30% by weight carbamide peroxide, about 0.1 to about 40% urea by weight; and a dermatologically acceptable carrier.
The topical composition of the invention can be useful in treating dermatological disorders. Examples of dermatological disorders that can be treated by the composition include disorders due to changes in normal keratinization, epidermal formation or pilosebaceous function, such as acne, psoriasis, seborrhea, ingrown hairs and pseudofolliculitis barbae, and hyperpigmented skin.
In one embodiment, the invention provides a method for treating a dermatological disorder comprising administering to a subject in need thereof a topical composition of the invention.
DETAILED DESCRIPTION OF THE INVENTION
Overview
Carbamide peroxide and urea are pharmacological agents useful for the treatment of dermatological disorders. However, carbamide peroxide and urea have generally been considered incompatible. Carbamide peroxide can be extremely unstable. Thus, stability of carbamide peroxide is an important factor in formulating compositions containing carbamide peroxide. Carbamide peroxide formulations are generally most stable under acidic conditions. However, urea containing formulations generally tend to be neutral to slightly alkaline.
The novel compositions disclosed herein combine the benefits of urea and carbamide peroxide and yet achieve a stable formulation. In one embodiment, such a composition is achieved by use of an optimized buffer system that maintains the pH of the formulation at an optimal acidic range.
Topical Composition
The invention provides topical compositions comprising carbamide peroxide and urea. The desired amount of urea and carbamide peroxide can vary from composition to composition depending on the particular disorder or disorders being treated, the severity of the disorder, the duration of the treatment, the other specific components of the composition being used, and like factors. In one embodiment, the carbamide peroxide can be present in the composition at a concentration from about 0.5% to about 30% by weight and the urea can be present from about 0.1% to about 40% by weight, relative to the weight of the composition. In another embodiment, the carbamide peroxide can be present in the composition at a concentration from about 4 to about 15% by weight. In yet another embodiment, the carbamide peroxide can be present in the composition from about 4.5% to about 9% by weight. In still another embodiment, the urea can be present from about 5% to about 20% by weight, relative to the weight of the composition.
In one embodiment, the compositions of the invention are acidic. Carbamide peroxide is generally most stable under acidic conditions, while urea containing formulations generally tend to be neutral to slightly alkaline. As disclosed herein, acidic compositions including both carbamide peroxide and urea tend to be more stable under acidic conditions. In addition to allowing formation of a stable composition, a pH in an acidic range is also therapeutically useful. Generally, traumatized skin tends to have a higher pH and skin healing is aided by maintaining a slightly acidic pH. Thus, the novel formulations of this invention combine the benefits of urea and carbamide peroxide and yet achieve a stable formulation by the use of an optimized buffer system which maintains the pH of the formulation at an optimal acidic range. According to one embodiment of the invention, the composition has a pH less than 9. In another embodiment, the compositions have a pH in the range of about 2.5 to about 9.
Any dermatologically acceptable carrier can be used in the compositions of the invention. As used herein, “determatologically acceptable carrier” refers to vehicles, diluents, carries, which can include adjuvants, additives, or excipients, known for use in dermatological compositions. The compositions of the invention include, but are not limited to, creams, ointments, solutions, lacquers, sticks, pledgets, wipes, cleansers and/or gels.
In one embodiment, the topical composition is a semi-solid at room temperature but is easily absorbed into the stratum comeum. The semi-solid composition can be a cream. Such a composition can include petroleum-based liquids and solid fractions as skin protectants. The solid skin protectant can be semi-solid. The solid skin protectant can be present in about 1.0% to about 20% in the composition and includes petrolatum or a synthetic or semi-synthetic hydrocarbon of the same nature as petrolatum. Mixtures of such ingredients can also be used. Liquid skin protectants can be petrolatum and contained in the composition in about 1.0% to about 20% and include any synthetic or semi-synthetic oleaginous liquid fraction. The liquid skin protectant can be mineral oil, which is a liquid mixture of hydrocarbons obtained from petroleum.
The compositions of the invention can include propylene glycol. Propylene glycol can be present in the composition up to about 5%. In one embodiment, propylene glycol is present in the composition at about 1% to about 5%.
The compositions can contain conventional preservatives, such as methyl paraben, propyl and butyl imidazolidinylurea, diazolidinylurea, methylchloroiso-thiazolinone and methylisothiazolinone. Although not to be held by theory, it is believed that the antibacterial properties of the urea and carbamide peroxide and propylene glycol allow the composition of the present invention to be free of conventional preservatives.
The present compositions can also contain dermatologically acceptable excipients, such as for example emulsifiers and thickeners. Among these are for example C
16
to C
18
straight or branched chain fatty alcohols or fatty acids or mixtures thereof. Examples of emulsifiers and thickeners include cetyl alcohol, stearyl alcohol, stearic acid, palmitic acid, nor mixtures thereof. Fatty acids or fatty alcohols may be present in from about 0.25 to 2 wt-%.
Another ingredient useful in the composition of the present invention may be glyceryl stearate, which is a monoester of glycerine and stearic acid, or other suitable forms of glyceryl stearate for example glyceryl stearate SE, which is a commercially available self-emulsifying grade of glycerol stearate that contains some sodium and/or potassium stearate. Glyceryl stearate may be in the composition anywhere from about 1 to about 3% by weight.
Xanthan gum is another ingredient which may be used in the present compositions. Xanthan gum is a high molecular weight heteropolysaccharide gum produced by pure-culture fermentation of a carbohydrate with Xanthomonas campestris. The gum is also commercially available from various sources.
The composition can be an emulsion including liposomes. The emulsion can contain a fatty phase in the range of about 5% to about 80% by weight. Typically, the

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