Description:FIELD OF THE INVENTION
[0001] The present disclosure relates generally to pharmaceutical formulations. More specifically, the disclosure is directed to a topical formulation for skin infections comprising eugenyl acetate and an extract of Curcuma longa. The present disclosure also provides a process of manufacturing the formulation.

BACKGROUND OF THE INVENTION
[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
[0003] Skin infections, such as bacterial and fungal infections, are common and can infect any individual of any age and gender. Red, itchy, and scaly rashes may be seen. Although they are treatable they have a tendency to reoccur for up to 40-60% of the times. Most of the topical ointments use synthetic active compounds or their derivatives to cure or prevent such dermal infections, however, there is a need for organic and plant-based alternatives which can treat the infections and prevent them from reoccurring. Plant-based components are also dermal friendly and environmentally friendly. They do not cause any adverse side-effects and prevent any marks on the skin. In many people the synthetic compound-based ointments are of no effect, especially people with weakened immune systems, those on high antibiotics, obese, diabetic or pregnant people. For such populations, plant-based alternatives are more suitable.
[0004] The present disclosure provides topical formulations for managing skin infections that comprises plant-based active components with no adverse side-effects.

OBJECTS OF THE INVENTION
[0005] An object of the present disclosure is to provide a pharmaceutical formulation for management of skin infections comprising natural active components.
[0006] An object of the present disclosure is to provide a pharmaceutical topical formulation comprising eugenyl acetate and an extract of Curcuma longa.
[0007] Another object of the present disclosure is to provide a process of manufacturing a pharmaceutical topical formulation for management of skin infections.

SUMMARY OF THE INVENTION
[0008] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in Detailed Description section. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.
[0009] The present disclosure aims to provide a plant-based pharmaceutical formulation for topical application in treatment, amelioration and prevention of skin infections.
[0010] In an aspect, the present disclosure provides a topical formulation for management of skin infections comprising eugenyl acetate and an extract of Curcuma longa.
[0011] In an embodiment, the eugenyl acetate may be present in a weight percentage range of about 8% v/v to about 50% v/v of the formulation.
[0012] In an embodiment, the extract of Curcuma longa may be present in a weight percentage range of about 8% v/v to about 50% v/v of the formulation.
[0013] In an embodiment, the formulation may further comprise one or more pharmaceutically acceptable excipient(s).
[0014] In an embodiment, the excipient may be selected from humectant, emollient, binder, emulsifier, gelling agent, ultraviolet-protection agent, buffering agent, coloring agent, flavoring agent, solvent, or combinations thereof.
[0015] In an aspect, the present disclosure provides a process of manufacturing a topical formulation for management of skin infections, comprising the steps of: (a) adding dropwise eugenyl acetate and an extract of Curcuma longa to a solvent with emulsifier followed by homogenization to give an emulsion; (b) ultra-sonicating the emulsion to provide a nano-emulsion; and (c) adding pharmaceutically acceptable excipients to the nano-emulsion and making up the volume with the solvent to give the formulation.
[0016] Other aspects of the invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learnt by the practice of the invention.

DETAILED DESCRIPTION OF THE INVENTION
[0017] The following is a detailed description of embodiments of the disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.
[0018] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
[0019] Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
[0020] In some embodiments, numbers have been used for quantifying weights, percentages, ratios, and so forth, to describe and claim certain embodiments of the invention and are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
[0021] Various terms as used herein are shown below. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.
[0022] As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.
[0023] Unless the context requires otherwise, throughout the specification which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense that is as “including, but not limited to.”
[0024] The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein.
[0025] All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
[0026] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified.
[0027] The description that follows, and the embodiments described therein, is provided by way of illustration of an example, or examples, of particular embodiments of the principles and aspects of the present disclosure. These examples are provided for the purposes of explanation, and not of limitation, of those principles and of the disclosure.
[0028] It should also be appreciated that the present disclosure can be implemented in numerous ways, including as a system, a method or a device. In this specification, these implementations, or any other form that the invention may take, may be referred to as processes. In general, the order of the steps of the disclosed processes may be altered within the scope of the invention.
[0029] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.
[0030] The following discussion provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus, if one embodiment comprises elements A, B, and C, and a second embodiment comprises elements B and D, then the inventive subject matter is also considered to include other remaining combinations of A, B, C, or D, even if not explicitly disclosed.
[0031] As described herein, the term ‘effective amount’ refers to the amount of the formulation required to bring about a change or improvement in a subject without side effects or overdosing.
[0032] The term ‘topical’ here means applying to the surface of keratinous tissue.
[0033] The term, "subject" as used herein refers to an animal, preferably a mammal, and most preferably a human. The term "mammal" used herein refers to warm-blooded vertebrate animals of the class 'mammalia' , including humans, characterized by a covering of hair on the skin and, in the female, milk-producing mammary glands for nourishing the young, the term mammal includes animals such as cat, dog, rabbit, bear, fox, wolf, monkey, deer, mouse, pig and human.
[0034] The term, ‘management’, or ‘treatment’ as used herein refers to alleviate, slow the progression, attenuation, prophylaxis or as such treat the existing disease or condition. Treatment also includes treating, preventing development of, or alleviating to some extent, one or more of the symptoms of the diseases or condition.
[0035] Present disclosure relates to topical formulations comprising plant-based active components of eugenyl acetate and Curcuma longa.
[0036] In an embodiment, the present disclosure provides a topical formulation for management of skin infections comprising eugenyl acetate and an extract of Curcuma longa.
[0037] In an embodiment, the eugenyl acetate may be present in a weight percentage range of about 8% v/v to about 50% v/v of the formulation, preferably about 10% v/v of the formulation.
[0038] In an embodiment, the eugenyl acetate may be synthesized or obtained commercially. In a preferred embodiment, the eugenyl acetate may be synthesized by esterification of essential oil of clove (Syzygium aromaticum) in a solvent-free system by a catalyst. The catalyst may be an immobilized lipase. In an embodiment, the essential oil may be obtained from the whole plant or from the root, leaves, shoot, fruits, rhizome, seed, stem, barks, flower, sap, bud or combinations thereof of Syzygium aromaticum; preferably the essential oil is obtained from the bud of Syzygium aromaticum. In a preferred embodiment, the essential oil may be obtained from the bud of Syzygium aromaticum by cold pressing.
[0039] In an embodiment, the extract of Curcuma longa may be obtained from the whole plant or root, leaves, shoot, fruits, rhizome, seed, stem, barks, flower, sap, bud or combinations thereof of the plant. In a preferred embodiment, the extract may be obtained from the rhizome of Curcuma longa.
[0040] In an embodiment, the extract of Curcuma longa may be a non-aqueous extract or aqueous extract. Non-aqueous extracts may be selected from alcoholic extracts, glycol extracts, or oil extracts. In a preferred embodiment, the extract may be obtained by alcoholic extraction. In an embodiment, alcohol used for extraction may be selected from ethanol, methanol, isopropyl alcohol or combinations thereof. In a preferred embodiment, a 70% isopropyl alcohol is used for extraction of Curcuma longa.
[0041] In an embodiment, the extract of Curcuma longa may be present in a weight percentage range of about 8% v/v to about 50% v/v of the formulation, preferably about 10% v/v of the formulation.
[0042] In an embodiment, the formulation may further comprise one or more pharmaceutically acceptable excipient(s). The excipient may be selected suitably to prepare the formulation.
[0043] In an embodiment, the excipient may be selected from humectant, emollient, binder, emulsifier, gelling agent, ultraviolet-protection agent, buffering agent, coloring agent, fragrance, solvent, preservative, surfactant or combinations thereof. However, a person skilled in the art would appreciate that any other excipient(s) may be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[0044] In an embodiment, the excipient may be present in a range of about 8% v/v to about 90%v/v of the formulation, preferably about 80% v/v of the formulation.
[0045] In an embodiment, humectant(s) includes but is not limited to, glycerine, propylene glycol, butylene glycol, pentylene glycol, sorbitol or mixtures thereof. However, a person skilled in the art would appreciate that any other humectant (s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[0046] In an embodiment, emollient(s) includes but is not limited to, glycerine, digylcerine, honey, castor oil, coconut oil, cocoa butter, shea butter, fatty acids, mineral oil, or combinations thereof. However, a person skilled in the art would appreciate that any other emollient(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[0047] In an embodiment, emulsifier(s) includes but is not limited to, polysorbate 80, polysorbate 60, polysorbate 20, polyethylene glycol (PEG), 2-amino-2-methylpropanol, fatty acid esters of PEG or combinations thereof. However, a person skilled in the art would appreciate that any other emulsifier(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[0048] In an embodiment, binder(s) includes but is not limited to, cellulosic derivatives (such as methylcellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, etc), polyacrylates (such as Carbopol, polycarbophil, etc), Povidone (all grades), Polyox of any molecular weight or grade, irradiated or not, maize starch, povidone, copovidone, corn starch, starch, polyvinylpyrrolidone (PVP), microcrystalline cellulose (Avicel@ -Avicel 101), or combinations thereof. However, a person skilled in the art would appreciate that any other binder(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[0049] In an embodiment, the ultraviolet-protection agent(s) includes but is not limited to, ethyl (2,6-dimethyl-pyran-4-ylidene) cyanoacetate, para-aminobenzoic acid, zinc oxide, kaolin, or combinations thereof. However, a person skilled in the art would appreciate that any other ultraviolet-protection agent can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[0050] In an embodiment, the gelling agent(s) includes but is not limited to, pectin, agar, guar gum, polysaccharides, polyacrylamides, or combinations thereof. However, a person skilled in the art would appreciate that any other gelling agent can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[0051] In an embodiment, the buffering agent(s) includes but is not limited to, 2-amino-2-methylpropanol, sodium citrate, potassium citrate, sodium citrate di-hydrate, citric acid, citric acid monohydrate, sodium bicarbonate, potassium bicarbonate, sodium di-hydrogen phosphate, potassium di-hydrogen phosphate or combinations thereof. However, a person skilled in the art would appreciate that any other buffering agent can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[0052] In an embodiment, the coloring agent(s) includes but is not limited to, erythrosine, mica, eosin or combinations thereof. However, a person skilled in the art would appreciate that any other coloring agent can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[0053] In an embodiment, the fragrance includes but is not limited to, winter cherry, rose, lavender, aloe vera, natural essential oils, or combinations thereof. However, a person skilled in the art would appreciate that any other fragrance can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[0054] In an embodiment, the solvent includes but is not limited to, methanol, ethanol, n-propanol, isopropanol, hexane, heptane, petroleum ether, cyclohexane, diethyl ether, diisopropyl ether, ethyl acetate, methyl acetate, ethyl formate, methyl formate, isobutyl acetate, n-butyl acetate, methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, acetone, ethyl methyl ketone, diisobutyl ketone, methyl isobutyl ketone, 1,4- dioxane, toluene, ammonia solution, glacial acetic acid, ammonium hydroxide, sodium hydroxide, calcium hydroxide, calcium carbonate, potassium hydroxide, potassium carbonate, water, or combinations thereof. However, a person skilled in the art would appreciate that any other solvent or a combination of solvents can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[0055] The excipient may be selected based on the type of formulation to be prepared. In an embodiment, the formulation may be in the form of a gel, paste, serum, foam, lotion, emulsion (oil-in-water, water-in-oil, water-in-oil-in-water or oil-in-water-in-oil), nano-emulsion, cream or ointment for topical application on the affected areas. In a preferred embodiment, the formulation is a topical gel formulation. The formulation may be a leave-on product that can be applied and left on the skin for a time period.
[0056] In a preferred embodiment, there is disclosed a topical gel formulation comprising eugenyl acetate, an extract of Curcuma longa, ethyl (2,6-dimethyl-pyran-4-ylidene) cyanoacetate, polysorbate 20, pectin, glycerine, 2-amino-2-methylpropanol, erythrosine, and water.
[0057] The formulation of the present disclosure has both anti-fungal as well as anti-bacterial properties. In a preferred embodiment, the formulation is effective on gram-negative bacteria and fungi by breaking their cell walls. The topical formulation may be applied directly or by a sponge on affected areas of the skin. The formulation may also be used for preventing the development of a skin infection.
[0058] The formulation can also reduce any oxidative damage to the skin. The formulation may also have sun protecting effect.
[0059] The formulation of the present disclosure does not produce any adverse side-effects. The unique formulation and process of its manufacture utilize the active compounds to their full potential and can reduce the chances of recurrence of infections permanently.
[0060] The formulation has synergistic effect and provides storage stability. It may be applied once or more times a day depending on the skin condition and as advised by a dermatologist.
[0061] In an embodiment, the present disclosure provides a process of manufacturing a topical formulation for management of skin infections, comprising the steps of: (a) adding dropwise eugenyl acetate and an extract of Curcuma longa to a solvent with emulsifier followed by homogenization to give an emulsion; (b) ultra-sonicating the emulsion to provide a nano-emulsion; (c) adding other pharmaceutically acceptable excipients to the nano-emulsion and making up the volume with the solvent to give the formulation.
[0062] In an embodiment, the eugenyl acetate is synthesized by esterification of essential oil of clove (Syzygium aromaticum) catalytically, in a solvent-free system by an immobilized lipase. In an embodiment, the extract of Curcuma longa may be a non-aqueous extract or aqueous extract obtained from rhizome of Curcuma longa. In a preferred embodiment, the extract of Curcuma longa is a 70% isopropyl alcohol extract of Curcuma longa.
[0063] In another embodiment, the present disclosure provides a method of treating, preventing or ameliorating a skin infection in a subject by topically administering a therapeutically effective amount of the formulation.
[0064] In an embodiment, the skin infection may be a dermal bacterial or fungal infection. In an embodiment, the skin infection may be one or more of dermatitis, eczema, Athlete’s foot (Tinea Pedis), Nail fungus (Onychomycosis), Jock itch (Tinea Cruris), Scalp ringworm (Tinea Capitis), Ringworm (Tinea Corporis), cellulitis, erysipelas, impetigo, folliculitis, furuncles and carbuncles. The formulation may be applied to flaky skin, itchy skin, sensitive skin or inflamed skin. The skin may be facial skin or non-facial skin.
[0065] While the foregoing describes various embodiments of the disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof. The scope of the invention is determined by the claims that follow. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art.
EXAMPLES
[0066] The disclosure will now be illustrated with working examples, which is intended to illustrate the working of disclosure and not intended to take restrictively to imply any limitations on the scope of the present disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice of the disclosed methods and compositions, the exemplary methods, devices and materials are described herein.
[0067] MATERIALS: Curcuma longa and Syzygium aromaticum essential oil were obtained from HiMedia. Novozymes® 435 was obtained from BioSolutions. All other chemicals for the purposes of the examples were obtained from Sigma.
[0068] Example 1: Preparation of Gel Formulation
[0069] A topical gel formulation was prepared as per the present disclosure for treatment of skin infections comprising the actives- Eugenyl acetate and extract of rhizome of Curcuma longa, or turmeric. Eugenyl acetate was obtained by esterification of essential oil of bud of Syzygium aromaticum, or clove, in a solvent-free system using Novozymes® 435 catalyst. The cold pressed essential oil from clove was purchased from HiMedia. Thereafter, esterification of the essential oil was performed catalytically.
[0070] The topical gel formulation was prepared as per the composition provided in Table 1. 1.5 mL of Tween 20 was added to 50 mL of water. Eugenyl acetate and extract of turmeric as obtained above were added through a syringe and homogenized at 4000 rpm for 30 minutes to give an emulsion. The emulsion was subjected to ultra-sonication (with an Ultrasonic probe sonicator, PCI analytics, 230 V; 50 Hz AC current) at 20 seconds interval for 20 min to obtain a nano-emulsion. Glycerine and propylene glycol were prepared and added along with the fragrance and coloring agent and mixed well. AMP and pectin were added to the solution for inducing cream-like base. The solution was topped with water in quantity sufficient to make up the formulation to 100 mL.
Table 1: Composition for topical gel formulation
Ingredients % w/v or v/v Function
Eugenyl acetate 10 % v/v Active ingredient (oil phase)
Turmeric extracts 10 % v/v Active ingredient, preservative (oil phase)
Ethyl (2,6-dimethyl-pyran-4-ylidene) cyanoacetate
4 % v/v Protection from UV rays
Tween 20 1.5 % v/v Emulsifier
Pectin 2 % w/v Gelling agent
Glycerine 5 % v/v Humectants, emollient and water binder
Propylene glycol 10 % v/v Humectants (hydrating) and helps active ingredients to penetrate the skin
2-amino-2-methylpropanol
(AMP) 4 drops Buffering agent, surfactant
Erythrosine q. s. Coloring agent
Rose water 0.5 % v/v Fragrance
Distilled water q. s. q. s. Aqueous phase

[0071] The foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.

We Claims:

1. A topical formulation for management of skin infections comprising eugenyl acetate and an extract of Curcuma longa; wherein the eugenyl acetate is present in a weight percentage range of 8% v/v to 50% v/v of the formulation; and wherein the extract of Curcuma longa is present in a weight percentage range of 8% v/v to 50% v/v of the formulation.
2. The formulation as claimed in claim 1, wherein the eugenyl acetate is synthesized by esterification of essential oil of Syzygium aromaticum by an immobilized lipase.
3. The formulation as claimed in claim 2, wherein the essential oil is obtained from whole plant or from root, leaves, shoot, fruits, rhizome, seed, stem, barks, flower, sap, bud or combinations thereof of Syzygium aromaticum.
4. The formulation as claimed in claim 1, wherein the extract of Curcuma longa is obtained from whole plant or from root, leaves, shoot, fruits, rhizome, seed, stem, barks, flower, sap, bud or combinations thereof of Curcuma longa.
5. The formulation as claimed in claim 1, wherein the eugenyl acetate is present in a weight percentage of 10% v/v of the formulation.
6. The formulation as claimed in claim 1, wherein the extract of Curcuma longa is present in a weight percentage of 10% v/v of the formulation.
7. The formulation as claimed in claim 1, wherein the formulation further comprises one or more pharmaceutically acceptable excipient(s).
8. The formulation as claimed in claim 7, wherein the excipient is selected from humectant, emollient, binder, emulsifier, gelling agent, ultraviolet-protection agent, buffering agent, coloring agent, fragrance, solvent, preservative, surfactant or combinations thereof.
9. The formulation as claimed in claims 1-8, wherein the formulation is a topical gel formulation comprising eugenyl acetate, an extract of Curcuma longa, ethyl (2,6-dimethyl-pyran-4-ylidene) cyanoacetate, polysorbate 20, pectin, glycerine, 2-amino-2-methylpropanol, erythrosine, and water.
10. A process of manufacturing a topical formulation for management of skin infections, comprising the steps of: (a) adding dropwise eugenyl acetate and an extract of Curcuma longa to a solvent with emulsifier followed by homogenization to give an emulsion; (b) ultra-sonicating the emulsion to provide a nano-emulsion; (c) adding other pharmaceutically acceptable excipients to the nano-emulsion and making up the volume with the solvent to give the formulation.