FORM 2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"TOPICAL COMPOSITION"
2. APPLICANT:
(a) NAME: CIPLA LIMITED
(b)NATIONALITY: Indian Company incorporated under the Companies Act, 1956
(c) ADDRESS: Mumbai Central, Mumbai - 400 008, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention and the manner in which it is to be formed.

FIELD OF INVENTION:
The present invention relates to topical composition comprising atleast one alkaloid and atleast one antioxidant, the manufacturing process thereof and use of the said topical composition for the treatment of skin disorders, particularly vitiligo.
BACKGROUND AND PRIOR ART:
Vitiligo is a common skin pigment disorder affecting 1% of the world population, the incidence varying between 0.1 - 9% in different countries. Vitiligo is defined as a 'circumscribed, acquired, idiopathic, progressive hypomelanotic skin disorder, which is characterized by the development of patchy depigmented macules due to progressive loss of melanocytes'.
Vitiligo also known as 'leukoderma' is a pigmentation disorder in which melanocytes, i.e. the cells that produce the pigment in the skin are destroyed. Destruction of these melanocytes leads to the appearance of white patches on different parts of the body. Similar white patches appear on the mucosal tissues that line the mouth, nose and the retina. The hair that grows on areas affected by vitiligo may sometimes turn white.
Although the precise etiology of vitiligo is still not known it has become quite clear in recent times that complex genetic, immunological, neutral and self-destructive mechanisms may interplay a role in its pathogenesis. According to autocytotoxic hypothesis, oxidative stress has been suggested to be the initial pathogenic event in melanocyte degeneration along with hydrogen peroxide accumulation in the epidermis of patients with such active disease.
The article (Determination of oxidative stress in vitiligo by measuring superoxide dismutase and catalase levels in vitiliginous and non- vitiliginous skin, Sravani P. V., Kishore Babu N., Gopal K.V.T., Raghu Rama Rao G., Athota Rama Rao., Bhagavatula M, Raghava Rao T., Indian Journal of Dermatology, Venerology and Leprology, May-June 2009, Vol 75, Issue 3, 268-271) mentions that recent studies carried out for investigating the pathophysiology of vitiligo exhibit the involvement of oxidative stress.

An alteration in the antioxidant pattern, with significant higher levels of superoxide dismutase (SOD) has been detected in the skin, erythrocytes, peripheral blood mononuclear cells and serum of vitiligo patients. Also, reduction in catalase activity has been demonstrated in the epidermis, peripheral blood mononuclear cells and in melanocytes. The article concludes the concept of possible systemic oxidative stress in vitiligo.
Free radicals such as superoxide anion (O2"), hydrogen peroxide (H2O2) and nitric oxide are the molecules that occur during several physiological and pathological processes. These free radicals are scavenged continuously by antioxidant enzymes such as SOD, catalase (CAT), glutathione peroxidase, glutathione reductase, beta carotene, vitamin C, vitamin E and other trace elements.
In normal conditions, SOD, an antioxidant enzyme catalyses the dismutation of superoxide anion (O2") into O2 and H2O2 and CAT converts H2O2 to O2 and H2O.
In oxidative stress, there is insufficient antioxidant activity leading to excessive accumulation of free radicals, which cause damage to cellular components such as protein, carbohydrate, DNA and lipid. Hence, in oxidative stress, to counteract or scavenge increased levels of superoxide anions (O2"), SOD is increased, whereas CAT levels are decreased. Hydrogen peroxide, thus produced from superoxide anions (O2'), can readily cross cell membranes, causing much of the damage.
Thus, impairment in the antioxidant system in vitiligo leads to free radical-mediated damage to melanocytes. Further, such an oxidative stress may be one of the reasons for the progressive nature of this disease. Hence, antioxidants may play a major role in the management of vitiligo in addition to the specific therapies.
Current treatments which are available for the treatment of vitiligo include the use of photosensitisers (e.g. psoralens) with UVA radiation (PUVA), corticosteroids or skin grafting. However, these remedies exhibit lower success rates and are generally accompanied by unpleasant side effects.

Certain plant remedies, usually administered as mixtures of herbs or extracts, particularly those used in traditional Chinese medicine and Indian Ayurvedic medicine, have been employed for the treatment of vitiligo since a long time. Herbs such as Psoralea corylifolia L. and Vernonia anthelmintica Willd. (Centratherum anthelminticum Kuntze) are very well known for their use in vitiligo. Psoralens, which are employed in the modern PUVA and khellin in KUVA therapy, were originally derived from plant sources {Psoralea corylifolia L and Ammi visnaga respectively) and are used as traditional remedies for vitiligo.
US20080146987 discloses a method of treating a skin condition such as vitiligo in an animal with a piperine based composition and further irradiating the skin.
WO0002544 discloses use of piperine or active analogues or derivative thereof for stimulating the proliferation of melanocytes.
Formulation and evaluation of piperine cream for vitiligo patients has been disclosed by Vinod K.R., Santhosha D. and Anbazhagan S. (Formulation and Evaluation of Piperine Cream- A New Herbal Dimensional Approach For Vitiligo Patients, Internationa! Journal of Pharmacy and Pharmaceutical Sciences, Vol 3, Suppl 2, 2011, 29-33).
Effect of UV radiation in the antivitiligo therapy by piperine topical formulation have been disclosed by Vinod K.R., Santhosha D., Anbazhagan S, Otilia Banji, David Banji, Sandhya S. Archives of Applied Science Research, 2010, 2 (4): 165-169.
Effects of piperine analogues on stimulation of melanocyte proliferation and melanocyte differentiation has been disclosed by Radhakrishnan Venkatasamy, Laura Faas, Antony R. Young, Amala Ramana and Robert C. Hider, Bioorganic & Medicinal Chemistry 12 (2004) 1905-1920.
WO9220341 discloses a method of ameliorating the adverse effects of aging on mammalian cells by administering to cells 6-(substituted amino) purine cytokinin.

However, most of these therapies rely on the use of UV irradiation for their efficacy, which is associated with the etiology of skin cancer. Also, some of these treatments exhibit serious side effects such as Cushing's syndrome, skin cancer and gastrointestinal disorders.
Hence, there still remains a need to formulate a suitable topical composition has reduced side effects, as well as effective for the treatment of vitiligo.
OBJECT OF THE INVENTION:
An object of the present invention is to provide a topical composition suitable for the treatment of vitiligo
Another object of the present invention is to provide a topical composition suitable for the treatment of vitiligo with reduced side effects.
Yet another object of the present invention is to provide a topical composition suitable for the treatment of vitiligo optionally with pharmaceutically acceptable excipients.
Still another object of the present invention is to provide a topical composition suitable for the treatment of vitiligo which is easy to manufacture.
SUMMARY OF THE INVENTION:
According to one aspect of the present invention there is provided a topical composition comprising atleast one alkaloid and atleast one antioxidant.
According to another aspect of the present invention there is provided a topical composition comprising atleast one alkaloid and atleast one antioxidant optionally with one or more pharmaceutically acceptable excipients.

According to a yet another aspect of the present invention there is provided a process of manufacturing the topical composition comprising atleast one alkaloid and atleast one antioxidant optionally with one or more pharmaceutically acceptable excipients.
According to another aspect of the present invention there is provided a method of treating vitiligo, which method comprises applying the topical composition comprising atleast one alkaloid and atleast one antioxidant optionally with one or more pharmaceutically acceptable excipients.
DETAILED DESCRIPTION OF THE INVENTION:
As discussed above, current treatments that are available for the treatment of vitiligo include the use of photosensitisers (eg psoralens) with UVA radiation (PUVA), corticosteroids or skin grafting which may exhibit potential side effects such as Cushing's syndrome, skin cancer and gastrointestinal disorders and hence there is a need to develop and formulate a topical composition which is suitable, provides reduced side effects, as well as effective for the treatment of vitiligo
The fruit of black pepper {Piper nigrum L.) and long pepper {Piper longum L) are both important medicinal herbs in Ayurvedic and Unani (traditional Indian) systems of medicine, in which the remedy generally consists of mixtures of herbs. A wide range of the medicinal uses of black pepper are known and have been documented including its use in the treatment of leucoderma.
Piperine, the major alkaloid found in the fruit of black pepper {Piper nigrum L.; Piperaceae), stimulates the replication of melanocytes and induces the formation of melanocytic dendrites. Piperine is expected to cause the repopulation of vitiligo patches through a stimulatory effect on perilesional and follicular melanocytes.
Piperine is chemically known as (1-2E, 4E-piperinoyl-piperidine) and is structurally represented as below.


Piperine has also been reported to occur in other Piper species i.e. P. acutisleginum, album, argyrophylum, attenuatum, aurantiacum, betle, cailosum, chaba, cubeba, guineense, hancei, khasiana, longum, macropodum, nepaleme, novae hollandiae, peepuloides, retrokacturn, sylvaticum.
Cytokinins are a class of plant hormones that play various roles in many aspects of plant development. N6-furfuryladenine (kinetin) is a degradation product of DNA, which promotes cell division in plants. Kinetin is an essential plant growth hormone that regulates the aspects of growth and differentiation, retards leaf yellowing and senescence, and slows down fruit ripening and degeneration. Kinetin is structurally represented as

Kinetin exhibits both in vitro and in vivo anti-oxidant activity. Kinetin acts as both an inhibitor of reactive oxygen species (ROS) formation as well as a scavenger of ROS. Kinetin also has the ability to mimic superoxide dismutase (SOD) activity, activate both SOD and catalase expression, and quench ROS. Also, kinetin further prevents the oxidation of unsaturated fatty acids and inhibits the in-vitro oxidation of DNA in plants. Further, kinetin can inhibit the oxidation and glycation/glycoxidation of proteins.
The inventors of the present invention have surprisingly found that a combination comprising piperine and kinetin exhibits therapeutic benefit for the treatment of vitiligo by stimulating the replication of melanocytes as well as reducing the oxidative stress.

In particular, the present invention provides a topical composition comprising piperine and kinetin.
In one embodiment of the present invention, there is provided a topical composition comprising piperine and kinetin with one or more pharmaceutically acceptable excipients.
As used herein, the term "pharmaceutically acceptable excipient" refers to those carriers,, compounds, materials, suitable for contact with the tissues of human beings and animals without producing any toxicity, irritation, allergic response, or any other problems or complications.
The term "Piperine" is used throughout the description in broad sense to include not only Piperine per se but also the extract prepared using any parts of the plant such as roots, stem, flower, fruit may be used. Any suitable commercially available Piperine extract may also be used provided that the said extract possesses re-pigmenting capacity.
For the purpose of the present invention, suitable extract of Piperine can be prepared using various extraction methods known in the art such as maceration, remaceration, digestion, agitation, agitation maceration, filtration, vortex extraction, centrifugation, ultrasonic extraction, countercurrent extraction, percolation, repermoiation, evacolation (extraction under reduced pressure), diacolation and solid liquid extraction under continuous reflux in a Soxhlet extractor.
The composition of the present invention is intended for topical application. In the context of the present invention, it is to be understood that the term "topical application" involves application to the skin as well as to the body cavities.
The dosage forms for topical application comprises spot-on, gel, spray, foam, cream, lotion, ointment, film, solution, liniment, patch and the like. The topical composition, of the present invention, may also be provided in a support base or matrix that may be directly applicable to a desired area of the skin. Examples of such support base include, but are not limited to gauze or bandages.

The topical composition, of the present invention, may further comprise pharmaceutically acceptable excipients as desired for any topical application.
The topical composition, of the present invention, comprises one or more pharmaceutically acceptable excipients such as oils, stabilizers, emulsifiers/surfactants, emollient, humectants, pH adjusting agents, propellants, organic or aqueous solvents, preservatives, gelling agents, chelating agents, film forming polymers, synthetic antioxidants, stiffening agent, skin conditioners, , moisturizers, soothing agents, thickeners, salts, fragrances, perfumes, colorants, and other excipients commonly incorporated in topical compositions.
Surface active agents, which may be employed in the topical composition of the present invention, can be selected from anionic surfactants, non-ionic surfactants, cationic surfactants, and amphoteric surfactants.
Examples of suitable anionic surfactants, include, but are not limited to, ammonium lauryl sulfate, sodium lauryl sulfate, ammonium laureth sulfate, sodium laureth sulfate, alkyl glyceryl ether sulfonate, triethylamine lauryl sulfate, triethylamine laureth sulfate, triethanolamine lauryl sulfate, triethanolamine laureth sulfate, monoethanolamine lauryl sulfate, monoethanolamine laureth sulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate, lauric monoglyceride sodium sulfate, potassium lauryl sulfate, potassium laureth sulfate, sodium lauryl sarcosinate, sodium lauroyl sarcosinate, lauryl sarcosine, cocoyl sarcosine, ammonium cocoyl sulfate, ammonium lauroyl sulfate, sodium cocoyl sulfate, sodium lauroyl sulfate, potassium cocoyl sulfate, potassium lauryl sulfate, triethanolamine lauryl sulfate, triethanolamine lauryl sulfate, monoethanolamine cocoyl sulfate, monoethanolamine lauryl sulfate, sodium tridecyl benzene sulfonate, sodium dodecyl benzene sulfonate, sodium and ammonium salts of coconut alkyl triethylene glycol ether sulfate; tallow alkyl triethylene glycol ether sulfate, tallow alkyl hexaoxyethylene sulfate, disodium N-octadecylsulfosuccinate, disodium lauryl sulfosuccinate, diammonium lauryl sulfosuccinate, tetrasodium N-(l,2-dicarboxyethyl)-N-octadecylsulfosuccinate, diamyl ester of sodium sulfosuccinic acid, dihexyl ester of sodium sulfosuccinic acid, dioctyl esters of sodium sulfosuccinic acid, docusate sodium, and combinations thereof.

Examples of suitable nonionic surfactants, include, but are not limited to,
polyoxyethylene fatty acid esters, sorbitan esters, cetyl octanoate, cocamide DEA.
cocamide MEA, cocamido propyl dimethyl amine oxide, coconut fatty acid diethanol
amide, coconut fatty acid monoethanol amide, diglyceryl diisostearate, diglyceryl
monoisostearate, diglyceryl monolaurate, diglyceryl monooleate, ethylene glycol
distearate, ethylene glycol monostearate, ethoxylated castor oil, glyceryl monoisostearate,
glyceryl monolaurate, glyceryl monomyristate, glyceryl monooleate, glyceryl
monostearate, glyceryl tricaprylate/caprate, glyceryl triisostearate, glyceryl trioleate,
glycol distearate, glycol monostearate, isooctyl stearate, lauramide DEA, lauric acid
diethanol amide, lauric acid monoethanol amide, lauric/myristic acid diethanol amide,
lauryl dimethyl amine oxide, lauryl/myristyl amide DEA, lauryl/myristyl dimethyl amine
oxide, methyl gluceth, methyl glucose sesquistearate, oleamide DEA, PEG-distearate,
polyoxyethylene butyl ether, polyoxyethylene cetyl ether, polyoxyethylene lauryl amine,
polyoxy ethylene lauryl ester, polyoxyethylene lauryl ether, polyoxyethylene nonylphenyl
ether, polyoxyethylene octyl ether, polyoxyethylene octylphenyl ether, polyoxyethylene
oleyl amine, polyoxyethylene oleyl cetyl ether, polyoxyethylene oleyl ester,
polyoxyethylene oleyl ether, polyoxyethylene stearyl amine, polyoxyethylene stearyl
ester, polyoxyethylene stearyl ether, polyoxyethylene tallow amine, polyoxyethylene
tridecyl ether, propylene glycol monostearate, sorbitan monolaurate, sorbitan monooleate,
sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate,
stearamide DEA, stearic acid diethanol amide, stearic acid monoethanol amide, laureth-4,
and combinations thereof.
Examples of suitable amphoteric surfactants include, but are not limited to, sodium N-dodecyl- -alanine, sodium N-lauryl- -iminodipropionate, rnyristoamphoacetate, lauryl betaine, lauryl sulfobetaine, sodium 3-dodecyl-aminopropionate, sodium 3-dodecylaminopropane sulfonate, sodium lauroamphoacetate, cocodimethyl carboxymethyl betaine, cocoamidopropyl betaine, cocobetaine, lauryl amidopropyl betaine, oleyl betaine, lauryl dimethyl carboxymethyl betaine, lauryl dimethyl alphacarboxyethyl betaine, cetyl dimethyl carboxymethyl betaine, lauryl bis-(2-hydroxyethyI)carboxymethyI betaine, stearyl bis-(2-hydroxypropyl)carboxymethyl betaine, oleyl dimethyl gamma-carboxypropyl betaine, lauryl bis-(2-

hydroxypropyl)aIpha-carboxyethyl betaine, oleamidopropyl betaine, coco dimethyl sulfopropyl betaine, stearyl dimethyl sulfopropyl betaine, lauryl dimethyl sulfoethyl betaine, lauryl bis-(2-hydroxyethyl)sulfopropyl betaine, and combinations thereof.
Examples of suitable cationic surfactants, include, but are not limited to, behenyl trimethyl ammonium chloride, bis(acyloxyethyl)hydroxyethyl methyl ammonium methosulfate, cetrimonium bromide, cetrimonium chloride, cetyl trimethyl ammonium chloride, cocamido propylamine oxide, distearyl dimethyl ammonium chloride, ditallowedimonium chloride, ditallow ammonium chloride, guar, hydroxypropyltrimonium chloride, lauralkonium chloride, lauryl dimethylamine oxide, lauryl dimethylbenzyl ammonium chloride, lauryl polyoxyethylene dimethylamine oxide, lauryl trimethyl ammonium chloride, lautrimonium chloride, methyl-1-oleyl amide ethyl -2-oleyl imidazolinium methyl sulfate, picolin benzyl ammonium chloride, polyquatemium, stearalkonium chloride, sterayl dimethylbenzyl ammonium chloride, stearyl trimethyl ammonium chloride, trimethylglycine, and combinations thereof.
Humectants provide the composition with smoothness and lubricity which, in turn, facilitate the application of composition. Suitable humectants, include, but are not limited to, polyhydric alcohols such as glycols, and polysaccharides, such as ethylene glycol, propylene glycol, butylene glycol, diethylene glycol, dipropylene glycol, glycerol, diglycerin, sorbitol, malvitol, trehalose, raffinose, xylitol, mannitol, polyethylene glycol, propylene glycol, polyglycerin, cholesterol, squaline, fatty acids, octyldodecanol, myristyl alcohol, urea, lanolin, lactic acid, esters such as isopropyl stearate, isopropyl myristate, isopropyl palmitate and isopropyl laurate and the like.
Suitable stiffening agents, which, may be employed in the topical composition of the present invention, comprise fatty alcohol, having a hydrocarbon chain containing 16 to 18 carbon atoms and having a melting point in pure state of about 45 °C to 65°C.
Examples of suitable stiffening agents include, but are not limited to, cetyl alcohol, stearyl alcohol, cetostearyl alcohol, eicosanol, docosanol, sorbitane monopalmitate, sorbitane monostearate, glyceryl monopalmitate, glyceryl monostearate, or glyceryl monopalmitostearate and combinations thereof.

The term "skin conditioner" refers to a substance which improves the quality of skin by providing a soothing effect and giving the skin a shine without greasiness.
Suitable skin conditioners, which may be employed, in the topical composition of the present invention include, but are not limited to, Medium chain triglycerides (MCTs) such as, Caprylic/Capric Triglycerides and the like.
Suitable stabilizing agents, which may be employed, in the topical composition of the present invention include, but are not limited to, myristyl lactate, isopropyl palmitate, light liquid paraffin, cetearyl alcohol, lanolin, lanolin derivatives, mineral oil, petrolatum, cetyl esters wax, cholesterol, glycerol, glycerol monostearate, isopropyl myristate, lecithin and combinations thereof.
Suitable emollients or waterproofing agents or film formers may also be incorporated in the topical composition of the present invention.
Examples of suitable emollients, which may be employed in the topical foam composition of the present invention, include, but are not limited to, dimethicone, polyhydric alcohols such as glycols, and polysaccharides, such as ethylene glycol, propylene glycol, butylene glycol, diethylene glycol, dipropylene glycol, glycerin, diglycerin, sorbitol, malvitol, trehalose, raffinose, xylitol, mannitol, polyethylene glycol, propylene glycol, polyglycerin, cholesterol, squaline, fatty acids, octyldodecanol, myristyl alcohol, urea, lanolin, lactic acid, esters such as isopropyl stearate, isopropyl myristate, isopropyl palmitate and isopropyl laurate and the like.
The term "moisturizer" refers to a substance designed to make the epidermis softer and more pliable, by increasing the extent of its hydration, allowing the addition of water to the epidermis, or the retention of water by the epidermis, or both.
Suitable moisturizers and/or occlusive moisturizers, which may be employed in the topical composition of the present invention, include, but are not limited to, white

petroleum jelly, aloe extract, urea, sodium lactate, and some amino acids, such as glycine or histidine and combinations thereof.
Suitable solvents, which may be employed, in the topical composition of the present invention, include, but are not limited to, glycerol, medium chain triglycerides and combinations thereof.
Suitable pH adjusting agents, which may be employed, in the topical composition of the present invention, include, but are not limited to lactic acid, sodium hydroxide, acetic acid, citric acid, tartaric acid, propionic acid, sodium phosphate, ammonia solution, triethanolamine, sodium borate, sodium carbonate, potassium hydroxide and like.
Suitable preservatives, which may be employed, in the topical composition of the present invention, include, but are not limited to. benzyl alcohol, hydroxybenzoates (parabens) such as Methyl Hydroxybenzoate, Propyl Hydroxybenzoate, Butyl Hydroxybenzoate, Ethyl Hydroxybenzoate, Benzoic Acid, , Phenoxyethanol, Chlorphenesin, Sorbic Acid, Phenoxyethanol, disodium edentate and combinations thereof.
Suitable gelling agents, which may be employed, in the topical composition of the present invention, include, but are not limited to, alginic acid, sodium alginate, potassium alginate, agar, carrageenan, pectin, gelatin, calcium alginate, carbomers, methyl cellulose, sodium carboxy methyl cellulose, cross linked acrylic acid polymers (e.g. carbopol), bentonite preferably carbomers may be used in combination with bioadhesives which includes, but not limited to, gelatin, carbopol 934, polycarbophil, cross-linked polymethacrylic acid, hydroxypropyl methyl cellulose, ethyl cellulose and combinations thereof.
Suitable chelating agents, which may be employed, in the topical composition of the present invention, include, but are not limited to, disodium edetate, sodium citrate, condensed sodium phosphate, diethylenetriamine pentaacetic acid and combinations thereof.

The topical composition of the present invention, may further comprise additional skin care active, which may include, but are not limited to, desquamatory actives, anti-acne actives, vitamin B3 compounds, peptides, hydroxy acids, synthetic anti-oxidants, radical scavengers, chelators, anti-inflammatory agents, topical anesthetics, tanning actives, skin lightening agents, anti-cellulite agents, flavonoids, antimicrobial actives, skin soothing agents, skin healing agents, antifungal actives, sunscreen actives, conditioning agents, structuring agents, thickening agents, and mixtures thereof.
Suitable synthetic antioxidants, which may be employed in the topical composition of the present invention, include, but are not limited to, α-tocopherol, BHT (butylhydroxytoluene) and BHA (butylhydroxyanisole) and combinations thereof.
Skin soothing agents are compounds having the ability to reduce the irritation or stinging/burning/itching effect of some chemicals.
Suitable soothing agents, which may be employed in the topical composition of the present invention, include, but are not limited to, German Chamomile extract, aloe, avocado oil, green tea extract, hops extract, colloidal oatmeal, calamine, cucumber extract, and combinations thereof.
Suitable anti-inflammatory agents which may be employed in the topical composition of the present invention, include, but are not limited to, panthenol, extract of Vitex negundo, extract of Commiphora myrrha, extract of Alchornea cordifolia, extract of Sideritis candicans, extract of Mallotus peltatus, extract of Pedialanthns tithymalodies, extract of Ocimum tamiifolium, Garcinia hanbuyri Hook, extract of Elephantopus tomentosus, extract of Rhus chirindensis, extract of Chrysanthemum indicum, extract of Ventilago harmandiana, Pothomorphe umbellate, extract of Forsythiae Fructus, extract of Lippia dulcis, extract of Nepeta sibthorpil Benham and combinations thereof.
In one embodiment, there is provided a topical composition in the form a lotion comprising piperine and kinetin optionally with one or more pharmaceutically acceptable excipients.

According to the present invention, there is further provided a process/method(s) of preparing the said topical composition which may be in the form of lotion, ointment, cream, spray, gel, foam, film, solution, liniment, patch and the like.
In one embodiment, there is provided a process of preparing the said topical composition which may be in the form of lotion.
According to the above mentioned embodiment, there is provided a method of
manufacturing the said topical composition in the form of a lotion comprising:
a. preparing an aqueous phase by adding chelating agent, humectant and emulsifier b.
preparing an oily phase by adding emulsifiers and emollients, c. preparing an water in oil
emulsion under homogenization. d. adding kinetin and piperine followed by remaining
ingredients.
Alternatively, the said topical composition in the form of a lotion may be prepared by a
process comprising:
a. preparing an aqueous phase by adding chelating agent, humectant and emulsifier b.
preparing an oily phase by adding emulsifiers and emollients, c. preparing an oil in water
emulsion under homogenization d. adding kinetin and piperine followed by remaining
ingredients.
According to the present invention, there is also provided a method for the treatment of vitiligo, which method comprises, applying the topical composition of the present invention comprising piperine and kinetin.
The following example is for the purpose of illustration of the invention only and is not intended in any way to limit the scope of the present invention.

Example 1:

Sr. No. Ingredients Qty/Unit (% w/w)
1. Kinetin 1.00
2. Piperine 0.50
3. Stearic acid 2.00
4. Cetyl alcohol 2.00
5. Medium chain triglyceride 3.00
6. Glyceryl Monostearate 1.50
7. Dimethicone 3.00
8. White petroleum Jelly 1.00
9. Phenonip-M 0.6
10. Glycerol 3.00
11. Disodium edetate 0.10
12. Alpha tocopheryl acetate 0.10
13. Chamomile Extract (German) 0.001
14. Aloe extract 0.05
15. Panthenol 1.00
16. Triethanolamine 0.60
17. Perfume 0.20
18. Purified water q.sto 100%
Process:
a) Preparation of aqueous phase
1. Disodium EDTA was dissolved in purified water.
2. Glycerin and Triethanolamine were added and mixed to the solution obtained in step (1)
3. The above phase obtained in step (2) was heated to approximately 75-80°C maintaining the temperature.

b) Preparation of oil phase
4. Stearic acid, Cetyl alcohol, Medium chain triglyceride, Glyceryl Monostearate and White petroleum Jelly were added and melted in another Stainless Steel vessel.
5. Dimethicone was added and mixed to the melt obtained in step (4).
6. The above phase obtained in step (5) was heated to approximately 75-80°C maintaining the temperature.
c) Preparation of emulsion
7. Oil in water emulsion was prepared under homogenization.
d) Addition of Piperine and Kinetin
8. Kinetin and Piperine along with remaining ingredients were added to the
emulsion obtained in step (7) at room temperature.
It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the spirit of the invention. Thus, it should be understood that although the present invention has been specifically disclosed by the preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and such modifications and variations are considered to be falling within the scope of the invention.
It is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," or "having" and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.
It must be noted that, as used in this specification and the appended claims, the singular forms "a," "an" and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to "a propellant" includes a single propellant as well as two or more different propellants; reference to a "cosolvent" refers to a single cosolvent or to combinations of two or more cosolvents, and the like.

WE CLAIM,
1. A topical composition comprising atleast one alkaloid and atleast one antioxidant optionally with one or more pharmaceutically acceptable excipients.
2. A topical composition as claimed in claim 1, wherein the alkaloid is piperine and the antioxidant is kinetin.
3. A topical composition as claimed in any of the preceding claims further comprising an excipient selected from oils, stabilizers, emulsifiers/surfactants, emollient, humectants, pH adjusting agents, propellants, organic or aqueous solvents, preservatives, gelling agents, chelating agents, film forming polymers, anti-oxidants, stiffening agent, skin conditioners, moisturizers, soothing agents, thickeners, salts, fragrances, perfumes, colorants.
4. A topical composition as claimed in claim 4, wherein the surfactant is selected from the group of anionic surfactants, non-ionic surfactants, cationic surfactants, amphoteric surfactants.
5. A topical composition as claimed in claim 4, wherein the humectant is selected from the group of ethylene glycol, propylene glycol, butylene glycol, diethylene glycol, dipropylene glycol, glycerol, diglycerin, sorbitol, malvitol, trehalose, raffinose, xylitol, mannitol, polyethylene glycol, propylene glycol, polyglycerin, cholesterol, squaline, fatty acids, octyldodecanol, myristyl alcohol, urea, lanolin, lactic acid, as isopropyl stearate, isopropyl myristate, isopropyl palmitate and isopropyl laurate.
6. A topical composition as claimed in claim 4, wherein the chelating agent is selected from the group of disodium edetate, sodium citrate, condensed sodium phosphate, diethylenetriamine pentaacetic acid.
7. A topical composition as claimed in claim 4, wherein the emollient is selected from the group of dimethicone, ethylene glycol, propylene glycol, butylene glycol, diethylene glycol, dipropylene glycol, glycerin, diglycerin, sorbitol, malvitol, trehalose, raffinose, xylitol, mannitol, polyethylene glycol, propylene glycol, polyglycerin,

cholesterol, squaline, fatty acids, octyldodecanol, myristyl alcohol, urea, lanolin, lactic acid, isopropyl stearate, isopropyl myristate, isopropyl palmirate and isopropyl laurate.
8. A topical composition as claimed in any of the preceding claims which is formulated as lotion, spot-on, gel, spray, foam, cream, ointment, film, solution, liniment, patch, gauze, bandage.
9. A process for preparing the topical composition which process comprises
a. preparing an aqueous phase by adding chelating agent, humectant and
emulsifier/surfactants
b. preparing an oily phase by adding emulsifiers/surfactants and emollients
c. preparing an water in oil emulsion or oil in water emulsion under
homogenization
d. adding kinetin and piperine followed by excipients.
10. A topical composition substantially herein described with reference to the
accompanying examples.