CLIAMS:------------ ,TagSPECI:The following specification describes the nature of the invention

TOPICAL COMPOSITIONS FOR THE TREATMENT OF ACNE

FIELD OF THE INVENTION
The present invention relates to the topical composition comprising Niacinamide and a moisturizer for the treatment of acne and the process for the preparation thereof. The invention also refers to the topical composition comprising Niacinamide and at least one moisturizer selected from natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent.

BACKGROUND OF THE INVENTION
Acne vulgaris is a skin disease of the sebaceous glands characterized by areas of the skin with seborrhea (scaly red skin), comedones (black heads and white heads), papules (pinheads), pustules (pimples), nodules (large papules) and possibly scarring. Severe acne is inflammatory, but acne can also manifest in non inflammatory forms. Acne occurs most commonly during adolescence and often continues in the adult hood. There are varieties of methods for treating acne vulgaris including topically applying various scrubbing or abrasive compositions, topically applying deep cleansing agents or astringent compositions and also applying ultraviolet radiation.
US Patent No. 4,505,896 provides the improved method and composition for the treatment of acne vulgaris involving the periodic application of an effective amount of niacinamide or combinations thereof with sulfur, salicylic acid, benzoyl peroxide, vitamin A, erythromycin base, clindamycin phosphate and tetracycline hydrochloride.
US Patent No. 7,182,963 discloses the cosmetic or dermopharmaceutical composition comprising the effective quantity of the oleanolic acid in the range of 1 ppm to about 10,000 ppm and nordihydroguaiaretic acid in the range of 1 ppm to 10,000 ppm for the treatment of acne, hyperseborrhea and acne prone skin. The composition disclosed in the US ‘963 Patent is available from Sederma France with the brand name Ac.netTM and contains the following ingredients as water (Aqua), butylene glycol, PEG-60 almond glycerides, caprylyl glycol, glycerin, carbomer, nordihydroguaiaretic acid and oleanolic acid. The composition as disclosed in US ‘963 patent at the concentration of 4% in combination with Niacinamide at the concentration of 4% is marketed as Lotion with the brand name Epiclear® in United Kingdom by Forever Young UK. The composition of Epiclear® lotion contains Ac.netTM, niacinamide, water, orange flower water, witch hazel, and glycerine. The Epiclear lotion® is used for the treatment of hyperseborrhea, hyper-keratinosis and acne.
The acne medications disclosed above on usage cause the skin to become red and peel easily due to its drying effect. So there exists a need to develop a topical composition that increases the moisture of skin, so as to increase the local tolerability of skin.

SUMMARY OF INVENTION
In one aspect the present invention relates to the topical composition comprising Niacinamide and atleast one moisturizer.
In another aspect the present invention relates to the topical composition comprising Niacinamide and at least one moisturizer selected from natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent.
In another aspect the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguiaretic acid, and at least one moisturizer.
In a further aspect the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguiaretic acid and at least one moisturizer selected from natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent.
In another aspect the present invention relates to the topical composition comprising Niacinamide and a moisturizing mixture.
In another aspect the present invention relates to the topical composition comprising Niacinamide and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent and natural moisturizing factors (NMF).
In another aspect the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguiaretic acid and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent and natural moisturizing factors (NMF).
In another aspect the present invention relates to the topical composition comprising Niacinamide and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent and potassium ion hydrating agent.
In another aspect the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent and potassium ion hydrating agent.
In another aspect the present invention relates to the topical composition comprising Niacinamide and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisturizing factors (NMF) and potassium ion hydrating agent.
In another aspect the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisturizing factors (NMF) and potassium ion hydrating agent.
In a further aspect the present invention relates to the topical composition comprising Niacinamide and a moisturizing mixture wherein the moisturizing mixture comprises a combination of natural moisture re-creating agent, natural moisturizing factors (NMF) and a potassium ion hydrating agent.
In a further aspect the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguiaretic acid and a moisturizing mixture wherein the moisturizing mixture comprises a combination of natural moisture re-creating agent, natural moisturizing factors (NMF) and a potassium ion hydrating agent.
In a further aspect the present invention relates to the topical composition comprising Niacinamide and a moisturizer wherein the topical composition is water based lotion or an oil-in-water emulsion.
In another aspect the present invention relates to the topical composition comprising Niacinamide and at least one moisturizer selected from natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent wherein the topical composition is water based lotion or an oil-in-water emulsion.
In a further aspect the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid and a moisturizer wherein the topical composition is water based lotion or an oil-in-water emulsion.
In another aspect the present invention relates to the process for the preparation of the topical emulsion composition comprising Niacinamide and at least one moisturizer wherein the process for preparation comprises the following steps
i) Forming a gel based water phase by adding the thickening/gelling agents to purified water and optionally adding other inactive ingredients.
ii) Forming the oil phase and
iii) Adding the oil phase to gel based water phase.

DETAILED DESCRIPTION OF THE INVENTION
The mammalian skin is composed of three layers; 1) Epidermis which provides water proofing and serves as a barrier to the infection; 2) Basement membrane which separates epidermis and dermis; 3) Dermis, which serve as location for the appendages of skin.
Hypodermis (not part of skin) lies below the dermis and its purpose is to attach the skin to underlying bone and muscle as well as supplying it with blood vessels and nerves.
The epidermis is the outermost layer of the skin and is a protective barrier over the body’s surface, responsible for keeping water in the body and preventing pathogens from entering into the body, and is a stratified squamous epithelium composed of proliferating basal and differentiated suprabasal keratinocytes. Keratinocytes are the major cells constituting 95% of the epidermis while merkel cells, melanocytes and langerhens cells are also present. The epidermis is further subdivided into five layers beginning with the outermost layer as follows; Stratum corneum, Stratum lucidum (only on palms and soles), Stratum granulosum, Stratum Spinosum, and Stratum basale.
The stratum corneum serves as the principal barrier against the percutaneous penetration of the chemical substances and microbial assaults and is capable of withstanding mechanical forces. The normal movement of water from the stratum corneum into the atmosphere is known as trans-epidermal water loss (TEWL). The stratum corneum is 10 to 20µm thick and contains a continuous sheet of protein enriched cells, embedded in an intracellular matrix, enriched in non polar lipids and organized as lamellar lipid layers called as corneocytes. On leaving the basal layer, keratinocytes begin to differentiate and undergo a number of changes in structure and composition during migration into stratum spinosum and stratum granulosum.
Keratinocytes synthesize and express numerous structural proteins and lipids during their maturation. Finally the keratinocytes are changed in the structure to transform into flat, anucleated squamous cells (corneocytes) of the stratum corneum, acting mainly with keratin filaments and surrounded by a cell envelope composed of crosslinked proteins called as cornified enveloped proteins as well as covalently bound lipid envelope. Extracellular non polar lipids surround the corneocytes to form a hydrophobic matrix. The cornified envelope proteins as well as the covalently bound lipid envelope are thought to be important for the chemical resistance of corneocytes. Desmosomes which interconnect adjacent keratinocytes are important for stratum corneum cohesion and are shed during the desquamation process in the stratum corneum.
The cornified envelope of the stratum corneum consists of a complex mixture of covalently cross-linked proteins coupled to plasmatic membrane of the cells. The components of the envelope are cross-linked mainly by the bonds via lysine ?-(?-glutamyl) isopeptide, catalyzed by calcium dependent glutaminases (candi etal. Nat Rev Mol Cell Biol. 2005 Apr; 6(4):328-40). This bonds lead to a protein complex highly insoluble and resistant to conventional biochemical extraction procedures. Various protein components are identified in the cornified envelope as keratins, filaggrin, trichohyalin, small proline-rich proteins (SPRPs), involucrins, loricrin, cystalin, desmoplaquin, elafin and proteins S100. The filaggrin undergoes further processing in the stratum corneum to release the free amino acids forming the component known as natural moisturizing factors (NMF) that assist in water retention. The natural moisturizing factors (NMF) are important to maintain the flexibility and osmolarity of the skin. Further the stratum corneum contains the natural moisturizing factors (NMF) such as lactates that are probably developed from the sweat and sugars (glucosylceramides from the Odland bodies produced in the stratum granulosum).
The major lipid classes in the stratum corneum are cholesterol, free fatty acids and ceramides. The free fatty acids are present in the range of 10% of the total mass of the lipids in the stratum corneum. The free fatty acids present in the stratum corneum ranges from C12-C24 carbon chain length. Ceramides are present in the range of 50% of the total mass of the lipids in the stratum corneum. Ceramides consist of long chains or sphingoid base (aliphatic chains of amines containing 2 or 3 hydroxy groups and trans-type double bond in position 4) attached to a fatty acid via an amide bond. The ceramides are covalently bound to cornified envelope proteins mostly involucrins. Ceramides are synthesized by serine-palmitoyl transferase as rate limiting enzyme and by hydrolysis of both glucosylceramide and sphingomyelin. The cholesterol is present in the range of 25% of the total mass of lipids present in the stratum corneum.
Further the ions such as calcium and potassium play an important role in homeostatic mechanism of the epidermal barrier function. In skin calcium is localized with high concentration in the granular layer and the potassium is highest in spinous layer.
Dermis is the third layer of the skin. It gives the skin its form, shape and elasticity. The dermis contains two layers 1) Stratum Papillare that consist of loose areolar connective tissue and 2) Stratum Reticulare that lies below the papillary region and is usually much thicker. It is composed of dense irregular connective tissue and contains oil glands (sebaceous glands), sweat glands, blood capillaries, nerve cells and hair follicles. The oil gland secretes an oily/waxy substance called sebum that is made of triglyceride oils, wax, squalene and metabolites of fat producing cells.
At adrenarche the oil glands in the dermis become overactive and secrete too much sebum (oil). Further the epithelium bordering the piloseba-ceous canal on hyperkeratinization secrets keratin. The keratin and sebum forms a microcomedo at the earliest stage. The microcomedo may enlarge to form an open comedo (blackhead) or closed comedo (whitehead). Whiteheads are the direct result of skin pores becoming clogged with sebum, naturally occurring oil, and dead skin cells. In these conditions the naturally occurring largely commensual bacteria Propionibacterium acnes can cause inflammation, leading to inflammatory lesions (papules, infected pustules, or nodules) in the dermis around the microcomedo or comedo, which results in redness and may result in scarring or hyper pigmentation to develop the acne.
The present invention is disclosed in the following embodiments
One embodiment of the present invention relates to the topical composition comprising Niacinamide and a moisturizer.
The present invention contains the Niacinamide as the anti-acne drug with potent anti-inflammatory effect where anti-inflammation is a major mechanism of anti-acne effect. The amount of Niacinamide used in the present anti-acne composition is preferably in the range of about 1% to about 10% by weight of the total composition, more preferably in the range of about 2% to about 7% by weight of the total composition, and most preferably in the range of about 4% by the total weight of composition. The concentration of about 4% of niacinamide for topical administration is extremely well tolerated by the facial skin and produces the beneficial effect in reducing the sebum production.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide and at least one moisturizer selected from natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent.
The present invention comprises at least one moisturizer selected from natural moisture re-creating agent, natural moisturizing factors (NMF), and potassium ion hydrating agent.
Natural moisture re-creating agents are the moisturizers that re-create the natural moisturizer from skin cells by stimulating the enzymes in the filaggrin metabolism to synthesize the natural moisturizing factors (NMF). The example of the natural moisturizing re-creating agent used in the present invention is the combination of ethylhexylpalmiate, sorbitan oleate, sorbitan laurate (and) myristyl malate phosphonic acid. It is available with the brand name RevidrateTM from Sederma France. The agents that re-create the natural moisture are preferably present in the range from about 0.1% to about 10% by weight of the total topical composition, more preferably in the range from about 0.3% to about 7% by weight of the total topical composition, and most preferably in the range from about 0.5% to about 5% by weight of the total topical composition.
Natural moisturizing factors (NMF) are the moisturizers that are generated naturally by the skin. In the present invention natural moisturizing factors (NMF) are added to the topical composition exogenously for the moisturizing effect. The natural moisturizing factors (NMF) are hydrophilic and hygroscopic. The natural moisturizing factors (NMF) are amino acids selected form the group of citrulline, glycine, serine or the mixtures thereof, organic acids selected from the group of uronoic acid, pyrrolidone carboxylic acid, lactate, glutamate or combinations thereof, and sugars selected from glucose. The preferred natural moisturizing factors (NMF) used in the present topical composition are salts of organic acids in the combination of sodium lactate and sodium gluconate. The combination of sodium lactate and sodium gluconate is commercially available with the trade name Purasal® Moist XS from Purac. The amount of natural moisturizing factors (NMF) is present preferably in the range from about 0.1% to about 20% by weight of the total topical composition, more preferably in the range from about 0.5% to about 15% by weight of the total topical composition, and most preferably in the range from about 1% to about 10% by weight of the total topical composition.
Potassium ion hydrating agent is the moisturizer which is natural osmoprotective compound abundant in potassium ions that are required to maintain the osmotic equilibrium of the skin cells. The potassium ion hydrating agent used in the present invention is imperata cylindrica root extract. The imperata cylindrica root extract is available with the brand name Moist 24® from Sederma France. The components of Moist 24® from Sederma France comprise imperata cylindrica root extract, water, glycerin, polyethylene glycol and carbomer. The amount of the potassium ion hydrating agent is present preferably in the range from about 0.1% to about 20% by weight of the total topical composition, more preferably in the range from about 0.5% to about 15% by weight of the total topical composition, and most preferably in the range from about 1% to about 10% by weight of the total topical composition.
The moisturizers may further include exogenous lipids and triglycerides.
Exogenous lipids: Ceramides and analogs thereof have the chemical structure as demonstrated below:

Triglycerides (butters and oils) : are selected from the group of caprylic acid (C8:0); capric acid (C10:0); lauric acid (C12:0); myristic acid (C14:0); palmitic acid (C16:0); palmitoleic acid (C16:1); margaric acid (C17:0); margaroleic acid (C17:1); stearic acid (C18:0); oleic acid (C18:10); linoleic acid (C18:2); linonenic acid (C18:3); arachidic acid (C12:0); gadoleic acid (C20:1) or mixtures thereof.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid, and a moisturizer.
The oleanolic acid and nordihydroguaiaretic acid used in the present invention is commercially available as oleanolic acid and nordihydroguaiaretic acid composition in an osmotic gel from Sederma France with the brand name Ac.netTM. The osmotic gel of Ac.netTM consists of water (aqua), butylene glycol, PEG-60 almond glycerides, caprylyl glycol, glycerin, and carbomer. The amount of oleanolic acid and nordihydroguaiaretic acid composition in osmotic gel is present in the current invention preferably in the range from about 0.1% to about 10% by weight of the total topical composition, more preferably in the range from about 1% to about 8% by weight of the total topical composition, and most preferably in the range from about 2% to about 5% by weight of the total topical composition.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid in an osmotic gel and a moisturizer.
A further embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid in an osmotic gel and a moisturizer wherein the osmotic gel consists of water (aqua), butylene glycol, PEG-60 almond glycerides, caprylyl glycol, glycerin, and Carbomer.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid and at least one moisturizer, selected from natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent.
A further embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid composition in an osmotic gel and at least one moisturizer selected from natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid composition in an osmotic gel and at least one moisturizer selected from natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent, wherein the osmotic gel consists of water (aqua), butylene glycol, PEG-60 almond glycerides, caprylyl glycol, glycerin, and Carbomer.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide and a moisturizing mixture.
The moisturizing mixture used in the present topical composition comprises the combination of at least two moisturizing agents selected from the combination of natural moisture re-creating agent and natural moisturizing factors (NMF), combination of natural moisture re-creating agent and potassium hydrating agent, combination of natural moisturizing factors (NMF) and potassium ion hydrating agent and triple combination of natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent. The mixture of the moisturizers in the double and triple combinations promotes the prolonged moisturizing effect to skin, so as to increase the local tolerability of skin when treated with the anti-acne drug Niacinamide. Further the mixture surprisingly produces the prolonged moisturizing effect exhibiting synergism because the moisturizers like natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agents each work with the different moisturizing mechanisms.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent and natural moisturizing factors (NMF).
A further embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent and natural moisturizing factors (NMF).
Another embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic composition in an osmotic gel and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent and natural moisturizing factors (NMF).
A further embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic composition in an osmotic gel and a moisturizing mixture, wherein the osmotic gel consists of water (aqua), butylene glycol, PEG-60 almond glycerides, caprylyl glycol, glycerin, and Carbomer; and the moisturizing mixture comprises the combination of natural moisture re-creating agent and natural moisturizing factors (NMF).
Another embodiment of the present invention relates to the topical composition comprising Niacinamide and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent and potassium ion hydrating agent.
A further embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent and potassium ion hydrating agent.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic composition in an osmotic gel and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent and potassium ion hydrating agent.
A further embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic composition in an osmotic gel and a moisturizing mixture, wherein the osmotic gel consists of water (aqua), butylene glycol, PEG-60 almond glycerides, caprylyl glycol, glycerin, and carbomer; and the moisturizing mixture comprises the combination of natural moisture re-creating agent and potassium ion hydrating agent.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisturizing factors (NMF) and potassium ion hydrating agent.
A further embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisturizing factors (NMF) and potassium ion hydrating agent.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic composition in an osmotic gel and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisturizing factors (NMF) and potassium ion hydrating agent.
A further embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic composition in an osmotic gel and a moisturizing mixture, wherein the osmotic gel consists of water (aqua), butylene glycol, PEG-60 almond glycerides, caprylyl glycol, glycerin, and Carbomer; and the moisturizing mixture comprises the combination of natural moisturizing factors (NMF) and potassium ion hydrating agent.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent.
A further embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent.
Another embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic composition in an osmotic gel and a moisturizing mixture wherein the moisturizing mixture comprises the combination of natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent.
A further embodiment of the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic composition in an osmotic gel and a moisturizing mixture, wherein the osmotic gel consists of water (aqua), butylene glycol, PEG-60 almond glycerides, caprylyl glycol, glycerin, and Carbomer; and the moisturizing mixture comprises the combination of natural moisture re-creating agent, natural moisturizing factors (NMF) and potassium ion hydrating agent.
In another embodiment the present invention relates to the topical composition comprising Niacinamide and a moisturizer wherein the topical composition is water based lotion or an oil-in-water emulsion.
In a further embodiment the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid and a moisturizer wherein the topical composition is water based lotion or an oil-in-water emulsion.
In another embodiment the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid composition in an osmotic gel and a moisturizer wherein the topical composition is water based lotion or an oil-in-water emulsion.
In another embodiment the present invention relates to the topical composition comprising Niacinamide, oleanolic acid and nordihydroguaiaretic acid composition in an osmotic gel, and a moisturizer, wherein the osmotic gel consists of water (aqua), butylene glycol, PEG60 almond glycerides, caprylyl glycol, glycerin and Carbomer; and the topical composition is topical water based lotion or a topical oil-in-water emulsion.
Topical water based lotion: The topical water based lotion composition of the present invention consists of only water phase i.e purified water which is present preferably in the range from about 5% to about 95% based on the total weight of the topical composition, more preferably in the range from about 10% to about 90% based on the total weight of the composition and most preferably the range of about 15% to about 85% based on the total weight of the topical composition.
A further embodiment of the present invention relates to the emulsions and the emulsions are of various types which are known in the art (e.g., oil-in-water emulsion, water-in-oil emulsion, water-in-oil-in-water, and oil-in-water-in-oil emulsions). The preferred embodiment of the present invention describes the topical emulsion composition having a continuous aqueous phase and a discontinuous oil phase. The oil phase of the present invention comprises silicone elastomers. However, the oil phase may also comprise non-silicone oils such as hydrocarbon oils, esters, ethers and the like.
The aqueous phase of the emulsion comprises water. The emulsion composition may comprise about 8% to about 90% of water. The aqueous phase may comprise components other than water including but not limited to conditioning agents, antimicrobials, humectants and other water skin care actives to impart an increased benefit to the keratinous tissue. In one embodiment the non-water component of the aqueous phase comprises a humectant such as glycerin and/or other polyols.
Silicone elastomers: The oil-in-water emulsion contains the silicone elastomers in the oil phase. The topical composition of the present invention comprises Cyclomethicone (and) Dimethicone Copolyol elastomer available as DC 3225C from Dow Corning. The amount of the silicone elastomer used in the composition ranges from about 0.1% to about 10% by weight to the total weight of the topical composition.
The topical compositions of the present invention further comprises the inactive ingredients selected from thickening agents/gelling agents, emulsifiers, higher alcohols, solid oils and fats, humectants, non ionic surfactants, anti-foaming agents, preservatives, antioxidants, buffering agents, anti tacking agents, chelating agents and any other inactive ingredients commonly used in the topical compositions.
Thickening agents/gelling agents: The topical compositions of the present invention may include one or more thickening agents. The composition may comprise from about 0.1% to about 5% of the thickening agent. Suitable classes of the thickening agents include but are not limited to carboxylic acid polymers, polyacrylamide polymers, sulfonated polymers, copolymers thereof, hydrophobically modified derivatives thereof and mixtures thereof. Suitable thickening agents include carboxylic acid polymers such as Carbomer (e.g, carbopol® 974, carbopol® 980, Carbopol 934, carbopol® 940 series), polyacrylamide polymers and copolymers available under the trade name Sepineo P 600 from Seppic corporation and combination of lecithin (and) sodium acrylate polymer available under trade name LecigelTM from Lucas meyer cosmetics.
Emulsifiers: The topical compositions of the present invention includes the emulsifiers selected from mixture glyceryl stearate (and)PEG-100 stearate, Sorbitan monostearate, Sorbitan monooleate, Sorbitan monolaurate, sorbitan monopalmitate, polysorbate60, PEG-400, glyceryl stearate, the mixture PEG-6/PEG-32/glycol stearate.
Higher alcohols: The higher alcohols used in the present topical compositions are selected from iso-stearyl alcohol, octyl dodecanol, hexyl decanol, cholesterol, stearic acid, bees wax, palmitic acid, glyceryl monostearate, glyceryl behenate, phytosterol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, behenyl alcohol and cetostearyl alcohol.
Solid oil or fats: The solid oils or fats used in the present topical compositions are selected from cacao fat, coconut oil, palm oil, palm nut oil, medium chain triglyceride, capryol 90, propylene glycol dicaprylate, olive oil, jojoba oil, isopropyl palmitate, isopropyl myristate, almond oil, hydrogenated oil, hydrogenated castor oil, Japan wax, Oliwax, Shea Butter, etc.
The humectants used in the present topical compositions are selected from glycerine, polyethylene glycol, and polyols such as propylene glycol and butylene glycol, hexylene glycol and/or combinations thereof.
The non-ionic surfactants used in the present topical compositions are selected from PEG60 almond glycerides available under the trade name CrovolTM A 70, PEG-192 Apricot kernel glycerides available under the trade name Crovol TM AK90, PEG-42 Babassu Glycerides available under the trade name CrovolTM BA70G, PEG-60 Corn Glycerides available under the trade name CrovolTM M70, PEG-60 evening Primrose Oil (and) Aqua available under the trade name CrovolTM EP 70/75. The preferred non-ionic surfactant used in the present water based lotion is PEG60 almond glycerides available under the trade name CrovolTM A 70.
The antifoaming agents used in the present topical compositions are selected from Cyclomethicone, Dimethicone, Simethicone or combinations thereof.
Preservatives: The preservatives used in the present topical compositions are selected from methyl paraben, Propyl paraben, Isobutyl paraben, Butyl paraben, Benzoic acid, Benzyl alcohol, Imidurea or the combinations thereof.
The antioxidant used in the present topical compositions is selected from Butylated hydroxy anisole, Butylated hydroxy toluene, Ascorbyl palmitate, Glutathione, ascorbic acid, citric acid, sodium metabisulphite, Ascorbyl acetate, sodium thiosulphate or combinations thereof.
The buffering agent used in the present topical compositions is selected from citric acid, sodium dihydrogen phosphate monohydrate, phosphoric acid, trisodium citrate and isothiozolidine diones.
The Antitacking agent used in the present topical compositions is selected from aluminum Starch octenylsuccinate, zinc oxide, polyamide 5 and titanium dioxide.
The chelating agents used in the present topical compositions are selected from disodium edetate, Carboxylates (e.g. Tartrate, Citrate or Gluconate), Phosphates (e.g. Sodium tri-phosphate or Tetra Potassium pyro-phosphate). The preferred chelating agent is disodium edetate.
Another embodiment of the present invention relates to the process for the preparation of the topical composition comprising niacinamide and atleast one moisturizer
Indian Patent application IN 4107/DELNP/2009 discloses the process for the preparation of the oil-in-water personal composition which discloses the process of the preparation of the oil-in-water emulsion comprising the steps of i) preparing the water phase; ii) preparing the oil phase; iii) combining the oil phase with water phase to form the oil-in-water emulsion and adding the thickening/agent to the oil-in-water emulsion. When the present inventors followed the process disclosed in 4107/DELNP/2009 Indian patent application it formed a high viscous emulsion (i.e 4000 cps) which is not suitable for application on acne lesions.
The present inventors has surprisingly discovered the drop in the viscosity of the emulsion (i.e 100-2500 cps) when the thickening agent/gelling agent was added as the part of water phase to which later the oil phase was added to form the oil-in-water emulsion.
Another embodiment of the present invention relates to the process for the preparation of the topical emulsion composition comprising niacinamide and atleast one moisturizer.
A further embodiment of the present invention relates to the process for the preparation of the topical emulsion composition comprising Niacinamide and at least one moisturizer wherein the process for preparation comprises the following steps
i) Forming a gel based water phase by adding the thickening/gelling agents to purified water and optionally adding other inactive ingredients
ii) Forming the oil phase and
iii) Adding the oil phase to gel based water phase.
Another embodiment of the present invention relates to the process for the preparation of the topical emulsion composition comprising Niacinamide and at least one moisturizer wherein the process for preparation comprises the following steps
i) Forming the gel based water phase by adding thickening/gelling agents to the purified water and further adding chelating agents, buffering agents and humectants.
ii) Forming the oil phase by heating the higher alcohols, antioxidants, preservatives, silicone elastomer, emulsifiers and solid oils or fats
iii) Adding the oil phase to the gel based water phase and
iv) Adding the Niacinamide, antitacking agent and at least one moisturizer selected from potassium ion hydrating agent and natural moisturizing factors (NMF) or mixtures thereof to step iii.
Another embodiment of the present invention relates to the process for the preparation of the topical emulsion composition comprising Niacinamide and a moisturizer mixture wherein the process for preparation comprises the following steps
i) Forming the gel based water phase by adding thickening/gelling agents to the purified water and further adding chelating agents, buffering agents and humectants
ii) Forming the oil phase by heating the higher alcohols, a moisturizer which is natural moisture re-creating agent, antioxidants, preservatives, silicone elastomer, emulsifiers and solid oils or fats
iii) Adding the oil phase to the gel based water phase and
iv) Adding the Niacinamide, optionally oleanolic acid and nordihydroguiaretic acid, antitacking agent and a moisturizing mixture of potassium ion hydrating agent and natural moisturizing factors (NMF) to step iii.
The general method of preparing the topical emulsion composition of the present invention is as follows. First the gelling agent/thickening agent is added to purified water and allowed to swell for about 15 to 20 minutes and chelating agents, buffering agents and humectants are added therein by heating the mixture at 50°C to 75°C to form the gel based water phase. The oil phase is prepared by heating at 50°C to 75°C the higher alcohols, a moisturizer which is natural moisture re-creating agent, antioxidants, preservatives, silicone elastomer, emulsifiers and solid oils or fats. Then the oil phase is added to the gel based water phase with gradual stirring to form an oil-in-water emulsion. Then Niacinamide, optionally oleanolic acid and nordihydroguiaretic acid, antitacking agent and moisturizing mixture of potassium ion hydrating agent and natural moisturizing factors (NMF) are added to the above oil-in-water emulsion while stirring.
Topical compositions of the present invention make them particularly interesting the treatment of acne juvenilis, acne vulgaris in the different comedones, papular, nodulo-cystic manifestations and in all situations where it is important to associate with sebum-regulating and antibacteric phenomena a strong anti-inflammatory effect. The topical compositions according to the present invention may also be proposed for the so-called acne from chemical or physical agents and for the folliculitis and moreover for the treatment of the seborrhoeic scalp, alopecia, seborrhoeic alopecia and seborrhoeic dermatitis.
Topical compositions of the present invention can be part of kit and filled into jars, bottles and any other forms of packaging that will allow ease of application topically, such as to the face, and any other superficial location prone to acne. The topical compositions are meant to be applied topically, either manually or by using a convenient applicator, for patient compliance and ease of application.
In embodiments the invention includes forms of packaging for topical compositions that are maintained during transportation, storage and use for commercially relevant times (e.g, 6 months, 12 months, 24 months or intermediate or longer periods). The topical compositions may be packed in tubes of glass, polymer of metal materials. Metal tubes may be made of aluminum or plastics, as they provide ideal barriers for products needing maximum protection and shelf life. A metal tube is advantageous as it is non-porous, light in weight, sanitary, durable, versatile, non-refillable, decorative, easy to handle, has a long shelf life and is adaptable to modern mass production methods and to automatic packaging.
Laminated tubes also may be used for packaging. The features and advantages of laminated tubes include ability to retain smoothness, flexibility and softness, increase in product shelf-life, excellent barrier properties, excellent sealability, resistant to print bleeding, tamper evident closures with nozzle seals available and hot foil stamping. In embodiments, the inventions provide the topical compositions for treatment of the acne in packages suitable for commercial scale that provide stability during storage or transportation. HDPE tubes can also be used for packaging of the topical compositions of the present invention. Pre-printed monolayer plastic tubes made of 100% HDPE by extrusion processes, with snap-on tamper evident caps or flip top tamper evident caps made up of polypropylene by injection molding processes are useful.
The present invention is further illustrated by the following examples which are provided merely to be exemplary of invention and don't limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

Example-1: Topical Composition (water-based lotion)
Ingredients Quantity
%w/w
Niacinamide 4
Ac.netTM 3
Disodium edetate 0.1
Sodium acrylate copolymer (and) lecithin
(LecigelTM) 4
Glycerine 8
Propylene glycol 10
Butylene glycol 3
PEG 60 almond glycerides 1
Potassium sorbate 0.5
Phenoxyethanol 1.5
Sodium lactate & gluconate
(Purasal® Moist XS) 7.0
Imperata cylindrica root extract, water, glycerin, polyethylene glycol and carbomer (Moist® 24) 6.0
Cyclomethicone 4.50
Purified water q.s.

Process for preparation:
1. In a suitable vessel, disodium edetate, potassium sorbate are added to water and stirred for complete mixing.
2. LecigelTM was added to the step 1 and stirred to ensure the complete swelling of the polymer.
3. Glycerine, butylene glycol, phenoxyethanol, PEG60 almond triglycerides, propylene glycol, is added to the contents of step 2 and stirred.
4. Cyclomethicone, Purasal® Moist XS, Ac.netTM are added to the contents of step no.3 and stirred.
5. Niacinamide was added to contents of step no.4 and made up with the purified water to the required volume.

Example-2: Topical composition (water-based lotion)
Ingredients Quantity
%w/w
Niacinamide 4
Ac.netTM 3
Disodium edetate 0.1
Ascorbic acid 0.02
Imperata cylindrica root extract, water, glycerin, polyethylene glycol and carbomer (Moist® 24) 4.5
Phenoxyethanol 1.5
Sorbic acid 0.45
Glycerin 10
Propylene glycol 7
Butylated hydroxy toluene 0.4
Carbopol 980 1.5
Sodium lactate & Gluconate (Purasal® Moist XS) 4.20
Purified water q.s.

Process for preparation:
1. In a suitable vessel, disodium edetate, sorbic acid, ascorbic acid are added to water and stirred for complete mixing.
2. Carbopol 980 was added to the step 1 and stirred to ensure the complete swelling of the polymer.
3. Glycerin, butylene glycol, propylene glycol, phenoxyethanol, are added to the contents of step 2 and stirred.
4. Butylated hydroxy toluene, Purasal® Moist XS, Ac.netTM are added to the contents of step no.3 and stirred.
5. Niacinamide was added to contents of step no.4 and made up with the purified water to the required volume.

Example-3: Topical composition (Oil in water emulsion)
Ingredients
Quantity
%w/w
Water Phase
Water Qs to 100%
Disodium edetate 0.3
Citric acid 0.8
Glycerin 9.0
Propylene glycol 10.0
Acrylamide/sodium acryloyd dimethyl taurate colpolymer & isohexadecane & polysorbate 80 (Sepineo P 600) 3.0
Oil Phase
Cetyl alcohol 3.0
Stearyl alcohol 1.0
Shea butter 1.2
Ethylhexylpalmiate, sorbitan oleate, sorbitan laurate (and) myristyl malate phosphonic acid (RevidrateTM) 2.0
Ascorbyl palmitate 0.06
Glyceryl stearate + PEG 100 stearate 2.7
Sorbitan monostearate 1.3
Butylated hydroxytoluene 0.5
Methyl paraben 0.3
Propyl paraben 0.3
Cyclotetrasiloxane (and) cyclopentasiloxane
(and) PEG/PPG-18/18 dimethicone
(DC 3225C) 2.0
Other Ingredients
Niacinamide 4
Ac.netTM 3
Imperata cylindrica root extract, water, glycerin, polyethylene glycol and carbomer (Moist®24) 2.8
Aluminum starch octenylsuccinate 0.80
Sodium lactate (and) sodium gluconate (Purasal® Moist XS) 3.8

Process for preparation:
1. In a suitable vessel Sepineo P600 was added to the purified water and allowed from 15 minutes to swell. Then disodium edetate, citric acid, glycerin and propylene glycol are added and heated at 50°C to 75°C to form the water phase.
2. In a separate suitable container cetyl alcohol, stearyl alcohol, Shea butter, RevidrateTM, ascorbyl palmitate, Glyceryl stearate (and) PEG 100 stearate, sorbitan monostearate, butylated hydroxy toluene, methyl paraben, propyl paraben, DC 3225C are combined and heated at 50°C to 75°C to form the oil phase.
3. The oil phase is combined with the water phase and homogenized to form the oil-in-water emulsion.
4. Niacinamide, Ac.netTM, aluminum starch octenylsuccinate, Moist® 24, Purasal® Moist XS are added to the contents of step3 to form the final product.

Example-4: Topical composition (Oil in water emulsion)
Ingredients Quantity
%w/w
Water Phase
Purified water Qs to 100%
Sodium acrylate copolymer & lecithin (LecigelTM) 2
Disodium edetate 0.1
Citric acid 0.3
Glycerin 5
Propylene glycol 10
Oil phase
Cetyl alcohol 2
Stearyl alcohol 1
Stearic acid 1
Shea butter 2
Glyceryl stearate citrate 0.5
Cyclomethicone 3
Oliwax 1
Glyceryl stearate (and) PEG-100 stearate 1
Sorbitan monostearate 1.5
Butylated hydroxy toluene 0.2
Methyl paraben 0.1
Propyl paraben 0.15
Cyclotetrasiloxane (and) cyclopentasiloxane
(and) PEG/PPG-18/18 dimethicone
DC 3225C 1
Other Ingredients
Niacinamide 4
Ac.netTM 3
Purasal® Moist XS 5
Moist® 24 3

Process for preparation:
1. In a suitable vessel Lecigel was added to the purified water and allowed from 15 minutes to swell. Then disodium edetate, citric acid, glycerin and propylene glycol are added and heated at 50°C to 75°C to form the water phase.
2. In a separate suitable container cetyl alcohol, stearyl alcohol, stearic acid, shea butter, glyceryl stearate citrate, Cyclomethicone, Oliwax, Glyceryl stearate (and) PEG 100 stearate, sorbitan monostearate, butylated hydroxy toluene, methyl paraben, propyl paraben, DC 3225C are combined and heated at 50°C to 75°C to form the oil phase.
3. The oil phase is combined with the water phase and homogenized to form the oil-in-water emulsion.
4. Niacinamide, Ac.netTM, Moist® 24, Purasal® Moist XS are added to the contents of step3 to form the final product.

Example-5: Topical composition (Oil in water emulsion)
Ingredients Quantity
%w/w
Water Phase
Purified water Qs to 100%
Sodium acrylate copolymer (and) Lecithin (LecigelTM) 2.2
Disodium edetate 0.18
Citric acid 0.22
Glycerin 7
Propylene glycol 8
Oil Phase
Cetyl alcohol 1
Stearyl alcohol 2
Shea butter 3
Ethylhexylpalmiate, sorbitan oleate, sorbitan laurate (and) myristyl malate phosphonic acid (RevidrateTM) 1.5
Glyceryl stearate (and) PEG 100 Stearate 1.5
Sorbitan monostearate 0.75
Butylated hydroxy toluene 0.1
Methyl paraben 0.2
Propyl Paraben 0.1
Ascorbyl palmitate 0.02
Other ingredients
Niacinamide 4
Ac.netTM 3
Imperata cylindrica root extract, water, glycerin, polyethylene glycol and carbomer (Moist®24) 2
Aluminum starch octenylsuccinate 1.5
Sodium lactate (and) sodium gluconate (Purasal® moist XS) 3

Process for preparation:
1. In a suitable vessel LecigelTM was added to the purified water and allowed from 15 minutes to swell. Then disodium edetate, citric acid, glycerin and propylene glycol are added and heated at 50°C to 75°C to form the water phase.
2. In a separate suitable container cetyl alcohol, stearyl alcohol, Shea butter, RevidrateTM, Glyceryl stearate (and) PEG 100 stearate, sorbitan monostearate, butylated hydroxy toluene, methyl paraben, propyl paraben and ascorbyl palmitate are combined and heated 50°C to 75°C to form the oil phase.
3. The oil phase is combined with the water phase and homogenized to form the oil-in-water emulsion.
4. Niacinamide, Ac.netTM, Moist® 24, Purasal® Moist XS, Aluminum starch octenylsuccinate are added to the contents of step3 to form the final product.