FIELD OF INVENTION The invention is in the field of topical preparations for skin. The invention specifically provides for topical preparations for skin treatment comprising of main ingredients as Azelaic acid and Tretinoin along with additional ingredients.

BACKGROUND OF THE INVENTION

Topical preparations are used for various skin treatment such as repairing, improving, partially or fully healing, or otherwise treating a wide variety of different skin disorders, diseases, conditions, maladies, dryness and/or the like, of the skin of mammals, such as inflammation, redness, hyperpigmentation, itching, bumps, blisters, cuts, punctures, other wounds, cracking, severe dryness, allergic reactions, insect bites, trauma, irritant dermatitis, contact dermatitis, seborrheic dermatitis, stasis dermatitis, perleche, psoriasis, eczema, eczema craquele, acne, allergies, other skin irritations, xerosis, disease related skin conditions and dryness from medications, or causing the skin to feel less painful, less irritated, less itchy, softened, soothed and/or conditioned.

Azelaic acid is a dicarboxylic acids medication for skin used to treat rosacea, melasma, post inflammatory hyperpigmentation, inflammatory papule and pustules, flushing and pimples on the face. Azelaic acid topical preparation is used to treat the pimples and swelling caused by acne. It treats rosacea by decreasing the swelling and redness of the skin. It may be working by killing the bacteria that infect pores and decreasing production of keratin, a natural substance that can lead to the development of acne. The common side effects of Azelaic acid application is sensation of burning, stinging and tingling besides itching, dry skin, irritation and erythema. There are also other less common side effects associated with

Azelaic acid application including contact dermatitis, edema, acne, facial burning, iridocyclitis after accidental exposure to the eyes, worsening of asthma/dyspnea/wheezing and serious allergic reactions. Tretinoin is another medication used for skin treatment. It is a retinoid medication used to treat acne, photo-aged skin and post inflammatory hyperpigmentation. It is used to decrease the number and severity of acne pimples and promote quick healing of pimples that do develop and it works by affecting the growth of skin cells. Following the Application of tretinoin to the skin leads to mild stinging or a sensation of warmth usually leads to local inflammation. The common side effects of tretinoin are dryness, scaling, itching, and redness.

Attempts have been made to combine Azelaic Acid and Tretinoin, the two effective skin medications, however, the side effects have always been a hinderance. The two medications are therefore usually advised by doctors to be used separately in view of the various associated side effects to ensure patient compliance.

SUMMARY OF INVENTION

The invention provides for a topical preparation for various skin ailments of formulation comprising Azelaic Acid and Tretinoin preferably with Vitamin C. The preferred concentration of said ingredients are 5% to 25% Azelaic Acid and 0.01% to 0.1%

Tretinoin along with 1% to 5% Vitamin C in stabilized form. The formulation may further comprise of Aloe vera, preferably as Aloe vera gel in concentration of 0.5 to 2.5% of the total formulation.

The most preferred formulation comprises of:

The preparation of present invention can be used for treatment of multiple skin ailments.

DESCRIPTION OF THE INVENTION

The two medications Azelaic Acid (of different therapeutic strengths) and Tretinoin (different therapeutic strengths) are available commercially as solo therapies for common skin ailments/indications or in combination with other ingredients but not together. The invention discloses skin formulations comprising both the medications together (in combination) for synergistic approach towards treating skin disorders minimal skin irritation, photosensitivity or other side effects.

When employed in the manner disclosed herein, the specific formulations including a unique combination of ingredients, and weight percent thereof, have surprisingly and unexpectedly been determined via experimentation and testing to function extremely well together, providing topical skin compositions that are extremely efficacious.

Vitamin C (Ascorbic Acid) is a potent antioxidant that can be used topically to treat skin ailments specifically to prevent changes associated with photoageing and for the treatment of hyperpigmentation, tissue inflammation. It may also be used for promotion of tissue healing

The unstable nature of Vitamin C and being difficult to deliver into the dermis in the optimum dosage have been a hindrance in the delivery of Vitamin C into the dermis. The invention discloses formulations comprising Azelaic Acid and Tretinoin along with Vitamin C to not only achieve the additional benefit of imparting the antioxidant benefits but also additionally providing mode of delivery of Vitamin C to the skin.

The combined formulation comprising the three ingredients wherein Azelaic Acid and Tretinoin are causing the respective effects on the skin with new cells being formed also allow for the Vitamin C to be delivered to the dei is appropriately.

The preferred formulation of the invention uses stabilized derivatives of Vitamin C as base for further improved efficacy. Stable ascorbic acid derivatives such as 3- Glyceryl Ascorbate are preferred. Stable derivatives such as Amitose 3GA produced by binding vitamin C (ascorbic acid) to glycerin has skin-moisturizing effect as well as inhibitory effect on melanin production. It enhances collagen production, and exerts an intracellular antioxidant effect. Therefore there is added advantage of Stabilized Vitamin C derivative as a skin antioxidant.

Along with this potent combination of Azelaic Acid and Tretinoin, the Vitamin C form in the formulation provides further advantages for the skin such as photoprotection, anti-aging effect, moisturizing and skin conditioning effect, greater stability (enhanced shelf-life) and skin whitening to name a few. Further excipients/ additives/ preservatives/inactives can also be used in the formulation of the invention including Cetyl Alcohol, Glyceryl Monostearate, Stearic Acid, Isopropyl Myristate, Gelot-64, Triethanolamine, PEG-4000, Phenoxyethanol, Allention, Glycerin, Menthol, Sepiclam, Fragrance Neo, Carbomer -980 and purified water Another embodiment of the invention is the use of Aloe vera as base of the formulation.

Aloe vera has known usage in treatment of skin ailments besides other benefits and was used as an adjunct in some of the combination formulations prepared in accordance with the invention.

The topical preparations of the invention include 5% to 25% Azelaic Acid concenteration and 0.01% to 0.1% Tretinoin besides other ingredients.

The topical preparations of the invention are preferably comprising stabilized Vitamin C and 10% Azelaic Acid strength along with 0.05% Tretinoin.

The topical preparations of the invention preferably also include Aloe vera.

Human volunteers were tested for the formulations prepared according to the instant invention to treat various skin ailments including acne (mild to moderate grades), hyperpigmentation (UV induced), skin aging, melasma and rosacea. The combination formulations were found to be effective in treating multiple skin ailments.

Different parameters were varied to arrive at various combinations and several formulations were identified where active ingredients was determined to be efficacious. The following parameters used as variables:

Type of inactives (excipients) used including solvents, thickening agents

Cone of such inactives (excipients)

Stage at which any ingredient was incorporated

Temperature at which the final product was formulated Consistency of the product (thickness, spreadability, texture, oil content)

Human Trials: about 50 formulations were tested on human subjects (volunteers) pH of the formulation

The inventions tested 50 formulation (actives + other ingredients) on human volunteers and after the trial, the volunteers reported marked reduction in skin irritation.

The formulation of the invention ensures reduced skin irritation and wide scope of treating multiple indications.

A preferred embodiment of the invention is a formulation comprising Azelaic Acid 10% and Tretinoin 0.05% with Aloe Vera and 3- Glyceryl Ascorbate (in base).

The invention therefore provides for a topical preparation for various skin ailments of formulation comprising Azelaic Acid and Tretinoin preferably with Vitamin C. The preferred concentration of said ingredients are 5% to 25% Azelaic Acid and 0.01% to 0.1 %

Tretinoin along with 1% to 5% Vitamin C in stabilized form. The formulation may further comprise of Aloe vera, preferably as Aloe vera gel in concentration of 0.5 to 2.5% of the total formulation.

The most preferred formulation comprises of:

EXAMPLES

The various preparations found to have the desired effect have been listed in the before provided examples as presented in Tables 1 to 6.

A preferred formulation as per the invention is provided in Table 1

Table 1

Another preferred formulation as per the invention is provided in Table 2

Table 2

Another preferred formulation as per the invention is provided in Table 3

Table 3

Another preferred formulation as per the invention is provided in Table 4

Table 4

Another preferred formulation as per the invention is provided in Table 5

Table 5

Another preferred formulation as per the invention is provided in Table 6

Table 6

There is additional advantage of improving patient compliance with single time application. Two solo therapies and that too with a time gap being usually recommended for treating certain skin disorders like acne is usually unsuccessful mainly due to patient noncompliance. The invention further encompasses methods for producing the above formulations, and methods of skin treatment for multiple ailments by topically administering or otherwise applying effective amounts of the composition thereof.

Various embodiments are possible of the invention other than those disclosed above and are easily comprehended by a person skilled in the art. The invention encompasses all such embodiments within its scope.