Abstract: ABSTRACT NOVEL BIODEGRADABLE FILM COMPOSITION OF PLANT BIO-ACTIVES FOR WOUND HEALING AND PROTECTION The present invention relates to the biodegradable polyherbal film composition comprising plant bio-actives for wound protection, wound healing, pain reduction and scar removal in burns and wounds, physical wounds, ischaemic wounds, Diabetic wound, pressure wounds, including acute and chronic wounds. The plant bio-actives present in the novel biodegradable film composition are quercetin, clove oil, nano curcuminoids, turmerone, tea tree oil and Asiaticosides.
DESC:RELATED DATA
The present application claims the benefit of priority to the Indian provisional patent application No 202341074187 filed on October 31, 2023 and entire provisional specification.
FIELD OF THE INVENTION
The present invention relates to a biodegradable polyherbal topical film forming composition comprising plant bio-actives. The plant bio-actives present in the biodegradable film composition are quercetin, clove oil, nano curcuminoids, turmerone, tea tree oil and Asiaticosides and pharmaceutically acceptable excipients.
The present invention further related to the process of preparing the biodegradable polyherbal topical film forming composition. The present invention also related to the method of treating and/or managing the wound using the biodegradable polyherbal topical film forming composition.
BACKGROUND OF THE INVENTION
The skin provides a protective barrier against physical, thermal, mechanical and chemical injury by preventing the body from dehydration and UV radiation and regulating body temperature. A wound is an injury involving the disruption of external or internal skin integrity. After an injury, wound healing proceeds through four overlapping stages, including coagulation, inflammation, re-epithelization and tissue remodelling. The ultimate goal of wound repair is to achieve tissue integrity and homeostasis. Coagulation involves platelet aggregation, providing a provisional extracellular matrix for cell migration. The inflammation occurs where white blood cells such as phagocytic cells, neutrophils and macrophages migrate to the injured site. At this stage, foreign particles, damaged cells, pathogens and microbes are removed from the wound area. Cytokines are released to promote fibroblast migration and proliferation. In the re-epithelization stage, new blood vessels are formed, so-called angiogenesis or neovascularization, to support perfusion to the newly generated tissues and extracellular matrix. The tissue remodelling phase involves collagen synthesis to strengthen the tissue. At this stage, the wound continues to contract, and fibres are reorganized to form a scar. The goal of wound healing enhancement is to accelerate wound repair, prevent infection, reduce pain, remove dead tissue, provide a moist environment, reduce edema and increase blood flow.
Acute and chronic wounds are susceptible to bacterial infection, leading to systemic infection, which is life-threatening. Bacterial infection also delays the wound healing process, resulting in prolonged inflammation. In chronic wounds, sustained inflammatory responses cause the accumulation of reactive oxygen species (ROS). A low level of ROS plays a critical role in angiogenesis at the wound site and regulates blood perfusion into the wound area. However, excess ROS can act as secondary messengers to recruit lymphoid cells to the wound site, thus preventing the transition of the wound from the inflammatory phase to the proliferative phase.
Medicinal plants have been the first line of treatment for trauma, infection, disease, and injury from prehistory. There are many ways by which wound can be healed, however the global trend has recently shifted from synthetic to herbal treatment. Many medicinal plants have been reported to possess wound healing activity and were found useful in the treatment of wounds. Secondary metabolites of plants have various beneficial effects on wound healing, including the enhancement of natural skin repair.
WO2001013955A1 discloses compositions and methods for delivering active agents to the skin of subject, including a polymer, an active ingredient and an alcohol are disclosed, the compositions being capable of delivery by rolling, spreading, aerosol or in droplets and of forming a film in contact with the skin.
US20210353699A1 discloses formulation comprising at least one medicinal plant, part or extract of it, one or more extracting agents and one or more pharmaceutically or cosmetically acceptable excipients that generate a plant extract (plant derivative) with a high bioactive content for regeneration of the skin, dermal mucous membrane and related parts, used as an active pharmaceutical ingredient to treat wounds of any kind or as a cosmetic ingredient for protection, maintenance and natural balance of the skin, dermal mucous membrane and related parts.
WO0072822A1 discloses use of an anti-infective and/or anti-inflammatory agent for the preparation of a pharmaceutical composition for the treatment of diseases of external or internal parts of the human or animal body which are susceptible to the administration of such agents.
US20190008907A discloses composition including a mixture of honey, curcumin, propolis or CAPE or any two of them is used to treat a variety of medical conditions. The composition can be administered topically, orally, by inhalation or parenterally. The composition is useful in treating wounds, infections, diabetes, skin conditions, renal conditions, dehydration, malnutrition, hypertension and various other conditions.
Conventional wound healing methods often come with limitations, such as slow recovery, risk of infection and unsightly scarring. These drawbacks have spurred the need for innovative solutions that accelerate healing while minimizing complications.
Conventional treatments, such as bandages, solutions and ointments, may be cumbersome to apply and require frequent changes, disrupting the healing process. Moreover, some treatments fail to address the multifaceted aspects of wound healing, leading to delayed recovery and unsatisfactory results.
Thus, inventors of the present invention have surprisingly found a novel approach that combines the therapeutic potential of bio-actives from herbal ingredients with advanced pharmaceutical technology. Inventors have combined traditional and modern experience to create more effective wound healing film forming spray composition. None of the prior arts discussed above discloses the invention of the present invention.
Surprisingly, the inventors have found polyherbal wound healing film-forming spray composition comprising nano curcumin, turmerones, quercetin, Asiaticosides and clove oil as herbal agents. The synergy of these plant bio-actives allows for faster and more effective tissue regeneration, reducing the risk of infections and scar removal. The polyherbal film-forming spray composition and delivery mechanism of the present invention create a protective barrier and harness the healing power of plant bio-actives. It not only accelerates healing but also offers the convenience of easy application. The biodegradable film formed also allows the plant bio-active to release in timely manner for better and longer absorption to skin tissues. It also provides for sustained release of the plant bio-actives so that the polyherbal film stay on the wound for about 1 to about 4 hours to provide wound protection and/or wound healing. This innovation will potentially revolutionize wound care, transforming a conventional process into a dynamic and efficient approach promoting faster healing, wound protection, reduced scarring, and improving patient outcomes.
The polyherbal film-forming topical spray of the present invention has the ability to address the drawbacks of conventional wound healing methods while connecting the potential of herbal ingredients with advanced pharmaceutical techniques.
SUMMARY OF THE INVENTION
The present invention provides polyherbal topical film forming spray composition for wound healing. The film provided is non-toxic, non-irritating and highly efficacious in treating wounds.
The present invention provides a polyherbal topical film forming spray composition comprising Nano Curcumin, Turmerones, Quercetin, Asiaticosides, Clove oil and a pharmaceutically acceptable excipient thereof. One or more pharmaceutically acceptable excipients selected from the group of biodegradable polymers, antioxidants, preservatives, permeation enhancer, fragrances, solvent, plasticizer, crosslinkers and propellants can be added in the composition of the present invention. The polyherbal topical film forming spray composition comprising about 0.5% to about 5% Nano Curcumin, about 1% to about 5% turmerones, about 0.5% to about 5% quercetin, about 0.01% to about 3% of Asiaticosides, about 0.1% to about 3% of clove oil, about 4% to about 12% of one or more biodegradable polymer, about 0.25% to about 2.5% of plasticizer, about 30% to about 60% of one or more propellant, and about 20% to about 80% of solvent. The polyherbal topical film forming spray composition further comprise of one or more additional active ingredients such as Tea tree oil, Lemon oil, Lavender oil, Camphor, Menthol, honey, Aloe vera extract, Ocimum sanctum extract, Citrus lemon peel extract, Witch Hazel Liquid extract, chamomile extract, Jojoba oil, Green tea extract, Pomegranate peel extract and Onion Oil extract.
The present invention further provides a method of wound healing, comprising applying topically the polyherbal topical film forming spray composition to a wound of a subject, wherein the pharmaceutical composition forms a film after application to protect the wound, to reduce the pain, to remove the scar and to improve wound healing.
Further the present invention provides a method of preparing polyherbal topical film forming spray composition comprising.
(i) dissolving biodegradable polymer in solvent in a closed vessel and divide into two parts;
(ii) mixing Turmerones and Nano curcumin until clear solution formed;
(iii) adding quercetin to step (ii);
(iv) adding clove oil to a portion of step (i);
(v) Mixing step (i) second portion with step (ii) in a closed vessel to make uniform solution, followed by step (iv) second part of solution;
(vi) Storing the solution of step(v) in closed holding tank to allow the solution to mature; and
(vii) Adding Step (vi) solution to closed filling tank and filling into aluminium cans followed by propellant addition and sealing the cans.
Moreover, the present invention provides the polyherbal topical film forming spray composition which provides wound healing and /or wound protection for a period of about 1 hour to about 4 hours.
Further, the present invention provides the polyherbal topical film forming spray composition which provides sustained release of polyherbal bio-actives for providing wound healing and /or wound protection for a period of about 1 hour to about 4 hours.
DESCRIPTION OF THE DRAWINGS
For a more complete understanding of the invention, reference should now be made to the embodiments illustrated in greater detail in the accompanying drawings and described by way of embodiments of the invention.
Fig 1: Illustrates drug release study of Curcumin
Fig 2: Illustrates mean Irritation Score
DETAILED DESCRIPTION OF THE INVENTION
In describing the embodiment of the invention, specific terminology is chosen for the sake of clarity. However, it is not intended that the invention be limited to the specific terms so selected and it is to be understood that such specific terms include all technical equivalents that operate in a similar manner to accomplish a similar purpose. As used herein, reference to an element by the indefinite article “a” or “an” does not exclude the possibility that more than one of the element is present, unless the context clearly requires that there is one and only one of the elements. The disclosure of numerical ranges should be understood as referring to each discrete point within the range, inclusive of endpoints, unless otherwise noted.
The terms abbreviated and used interchangeably in the specification are as described.
For purposes of the present invention, the terms "active agent", "drug" and medicament or herbal drugs or polyherbal drug or plant bio-actives are used interchangeably, and are meant to encompass a compatible bio-actives contained in the polyherbal film forming spray composition of the invention.
The term "comprising" is an inclusive term interpreted to mean containing, embracing, covering or including the elements listed following the term, but not excluding other unrecited elements.
The term composition or formulation or dosage forms are used interchangeably.
For purposes of the invention, the term "controlled release", "sustained release", and similar terms are used to denote a mode of active agent delivery that occurs when the active agent is released from the delivery vehicle at an ascertainable and controllable rate over a period of time, rather than dispersed immediately upon application. The controlled or sustained release formulations of the invention preferably provide a sustained action in the localized area to be treated. For example, it would be desirable that such a formulation provides localized wound healing to the site for a period of time e.g., few hours. The formulations can therefore, of course, be modified in order to obtain such a desired result.
As used herein, the term "treating" or "treatment" of a disease includes preventing the disease from occurring in subject that may be predisposed to the disease but does not yet experience or exhibit symptoms of the disease (prophylactic treatment), inhibiting the disease (slowing or arresting its development), providing relief from the symptoms or side-effects of the disease (including palliative treatment), and relieving the disease (causing regression of the disease). For the purposes of this disclosure, a "disease" includes wound. The term “treating wound” or “would healing” is use alternatively.
As used herein, the term "biodegradable polymers" refers polymers which get decomposed under aerobic or anaerobic conditions, as a result of the action of microorganism/enzymes. The biodegradable polymers used in the invention are non-toxic, non -irritating, easily spreadable, and form a film of herbal actives to provide protection to wounds from air, water and contamination for about 1 to about 4 hours and provide sustained release effect.
As used herein, the term "topically active" refers to a film formulation in accordance with the present invention which includes active agent which treats predominately the surface on which it is applied.
For purposes of the present invention, all percentages described herein are "w/w" unless otherwise specified. Also all percentages are based on total weight of the composition.
For purposes of the present invention, the wound is an incised wound, a lacerated wound, a penetrating wound, a perforated wound, a puncture wound, an open wound, a subcutaneous wound, a closed wound ischemic wounds, diabetic wound, pressure wounds including acute and chronic wounds and a combination thereof. In another embodiment the wound is a consequence of a disease or disorder, surgery, accident and a combination thereof. In yet another embodiment, the wound is acute or chronic wound. In yet another embodiment, the wound is external wound, internal wound and a combination thereof.
"Pharmaceutically acceptable excipient" or "excipient" or "inactive ingredient" includes, but is not limited to, a combination of drug compound of the present invention to produce a dosage form for topical administration. Any inert material that is combined is included. The term "pharmaceutically acceptable excipient" including but not limited to any emollient/stiffening agent/ointment base, emulsifying agent/solubilizing agent, humectant, thickening/gelling agent, biodegradable polymer, preservative, permeation enhancer, plasticizer, crosslinkers, propellant, chelating agent, antioxidant, acidifying/alkalizing/buffering agent, vehicle/solvent, protective agent, buffer, adjuvant, bioavailability promoter carriers, solubilizers (including surfactants), wetting agents, dispersants, suspending agents, fragrance and stabilizers shall be included.
According to an embodiment, the polyherbal topical film forming spray composition of the present invention comprises atleast one excipient. However, those skilled in the art will appreciate that it is possible to utilize other excipients without departing from the scope of the present invention. The excipients are commercially manufactured and available through various companies.
The therapeutically effective amount administered to the patient, e.g., a mammal, particularly a human, in the context of the present invention should be sufficient to affect a therapeutic or prophylactic response in the patient over a reasonable time frame. The dose can be readily determined using methods that are well known in the art. One skilled in the art will recognize that the specific dosage level for any particular patient will depend upon a variety of potentially therapeutically relevant factors.
As used herein, and unless otherwise indicated, the terms “manage,” “managing,” and “management” encompass preventing, delaying, or reducing the severity of a recurrence of immune modulatory disorders in a patient who has already suffered from such a disease or condition. The terms encompass modulating the threshold, development, and/or duration of the immune-modulatory disorders or changing how a patient respond to the immune-modulatory disorders.
The term "subject" includes mammals (especially humans) and other animals, such as domestic animals (e.g., household pets including cats and dogs) and non-domestic animals (such as wildlife).
The present invention is directed to a polyherbal topical film forming spray composition comprise of Nano Curcumin, Turmerones, Quercetin, Asiaticosides, clove oil and pharmaceutically acceptable excipients thereof.
The bioactives Turmerones, Nano curcumin, and Clove oil were received from the manufacturer Flavones Extracts, 223/224, Palamangalam, Narayanvanam Manadal, Tirupati dist., Andhra Pradesh. The quercetin is received from the manufacturer Pancea biotech, 905/906, 9th Floor, Earth arise, Nr. YMCA Club, SG Highway Road, Makarba, Ahemadabad -380015, Gujurat. Asiaticosides received from the manufacturer Indo-Napcop, Vshnukundina Nagar, Vinukonda, Guntur dist., Andra Pradesh. The Tea tree oil, Camphor and Menthol is received from AG Industries, B-55, sector 83, Noida-201305, UP.
The plant bio-actives have polyphenolic bioactive such as nano curcumin which helps to prevent would healing process along with anti-inflammatory, antifungal, antimicrobial activities and collagen synthesis at wound site. The bioactive oxygenated sesquiterpenes (Turmerones) act as functional ingredient which enhance absorption of polyherbal actives for penetration to cells, enhance film strength and exert faster anti-inflammatory, antifungal and antimicrobial actions. Clove oil will exert analgesic effect or give nubbiness/cooling effect. Quercetin is one of the important bioflavonoids which provide powerful antioxidant and anti-inflammatory effects, which support in wound healing. Centella Asiatica and its bioactive constituent, Asiatic acid or Asiaticosides act in one or more phases of cutaneous repair process.
Turmeric contains volatile oils known as turmerones and about 3%–4% curcuminoids. Curcumin (diferuloylmethane) constitutes 90% of the total curcuminoids. Nano curcumin or turmeric extract is obtained from solvent extraction of curcumin. The solvent commonly used are organic solvents such as ethylacetate. Curcumin has a hydrophobic polyphenol structure which provides wound healing properties. Curcumin is extracted from Curcuma longa and regulates the intracellular signal pathways which control the growth of cancerous cell, inflammation, invasion and apoptosis. It is known that curcumin nanoparticles enhance the solubility of curcumin by improving bioavailability more than 5 times from simple curcumin powder (J Med Food 15 (3) 2012, 242–252).
Turmerone is a naturally occurring compound found in turmeric. It belongs to the class of sesquiterpenes and possesses distinct properties and applications in scientific research. Turmerone is known for its antioxidant and anti-inflammatory properties. It is one of the major constituents present in the essential oil derived from the rhizomes of Curcuma longa, a perennial plant belonging to the ginger family, Zingiberaceae. This compound has been traditionally used in Asian medicines due to its therapeutic potential. Turmerone is obtained by steam distillation process form turmeric.
Quercetin is one of the important bioflavonoids present in more than twenty plants material and which is known for its anti-inflammatory, antihypertensive, vasodilator effects, antiobesity, antihypercholesterolemic and antiatherosclerotic activities. It is one of the most abundant dietary flavonoids found in fruits (mainly citrus), green leafy vegetables as well as many seeds, buckwheat, nuts, flowers, barks, broccoli, olive oil, apples, onions, green tea, red grapes, red wine, dark cherries, and berries such as blueberries and cranberries. The highest concentrations of flavones were found in vegetables such as onions and broccoli, fruits such as apples, cherries, and berries, and drinks such as tea and red wine. It is known that quercetin can promote the wound healing process by modulating inflammatory cells and increasing fibroblast proliferation while decreasing immune cell infiltration, fibrosis and scar formation, and creating changes in signaling in fibrosis-associated signaling pathway. It is extracted from onion oil through cold press method.
Flavonoids, plant sterols, eugenol and pentacyclic triterpenoids are among the several interesting phytochemical constituents found in the Centella Asiatica (L.) Urban is a small perennial herbaceous plant, belonging to the Apiaceae family and widely spread in the Southeast Asian countries, such Malaysia and Indonesia, where it is commonly known as Gotu kola, mandukparni, Indian pennywort, jalbrahmi and pegaga Nyonya. Centella asiatica and its bioactive constituent, asiatic acid or Asiaticosides act in one or more phases of cutaneous repair process. They display activity in tissue regeneration, cell migration and wound repair process by promoting inhibition of pro-inflammatory mediator’s release and immune cells migration in injured tissue as well as fibroblast proliferation and extracellular matrix and collagen synthesis. The benefits associated with the antimicrobial activity of this plant and its chemical components should contribute in a complementary way, inhibiting infections during healing. The extract of Centella asiatica also called as asiaticosides is prepared by solvent extraction using methanol.
Clove oil is an essential oil that’s derived from clove trees. The clove tree, known as Syzygium aromaticum, is native to Southeast Asia. Clove oil is produced by distilling the dried flower buds that are collected from the clove tree. Other parts of the tree, such as the stem and leaves, may also be used. Clove oil, which ranges in color from colorless to light yellow and has a strong, spicy aroma, has been used for centuries in a variety of applications. Clove oil is well established as an analgesic and anti-inflammatory agent. Its primary bioactive compound eugenol (around 80%), along with derivatives like a-caryophyllene, acetoeugenol and humulene among others, have potent antimicrobial, antioxidant, anti-inflammatory and antipyretic properties. Clove oil is extracted by non-solvent extraction from dried flower buds that are collected from the clove tree.
Another embodiment of the present invention is the polyherbal topical film forming spray composition comprising Nano Curcumin, Turmerones, Quercetin, Asiaticosides, clove oil, a pharmaceutically acceptable excipient and other additional plant bio-actives.
Another embodiment of the present invention is the polyherbal topical film forming spray composition comprising Nano curcumin complexed with Turmerones absorbed into Acrylates copolymer to exert sustain the release of bioactive to inflated skin.
Another embodiment of the present invention, the additional plant bio-actives which can be present in the polyherbal wound healing film forming spray composition include following but not limited to tea tree oil, Lemon oil, Lavender oil, Camphor, Menthol, honey, Aloe vera extract, Ocimum sanctum extract, Citrus lemon peel extract, Witch Hazel Liquid extract, chamomile extract, Jojoba oil, green tea extract, Pomegranate peel extract, Onion Oil extract.
These additional actives are also responsible for providing wound healing properties. Any other herbal compound or extract which has wound healing property can be added as an additional agent in the present invention.
In another embodiment, the pharmaceutical excipient/s in the polyherbal topical film forming spray composition can be selected from biodegradable polymers, antioxidants, preservatives, permeation enhancer, fragrance ingredients, solvent, plasticizer, crosslinkers, propellants or combination thereof.
In another embodiment, polyherbal topical film forming composition further comprises an effective amount one or more biodegradable polymers which forms film on wound surface. The biodegradable polymers are those polymers which get decomposed under aerobic or anaerobic conditions, as a result of the action of microorganism/enzymes. The biodegradable polymer present in the polyherbal would healing film forming spray composition can be selected from acrylic acid derivatives as acrylates copolymers or acrylate copolymers particularly ammonio methacrylate copolymer type a and ammonio methacrylate copolymer type b, (Eudragit®, RL and RS) cellulose derivatives such as hydropropyl methyl cellulose, ethylcellulose, carboxymethyl cellulose or hydroxy ethyl cellulose, polysaccharides, polyvinyl alcohol, polyethylene polypropylene, PVP, polyoxyethylene-polyoxypropylene block copolymer, carbomers, poloxamer, chitosan, gelatin, alginate, cyclodextrin derivatives, lactose, starch, cellulose, crosslinked polyacrylic acid polymers, xantham gum, pectin, polylactide, polycaprolactone, polyanhydrides, polyorthoesters, polyglycolides, polyethylene glycols, polyamides, polyurethanes, polyesteramides, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(amino acids), poly(methyl vinyl ether), and copolymers, terpolymers or combination thereof. Preferably, the amount of biodegradable polymer in the polyherbal wound healing film forming composition is about 1% to about 30%, more preferably the amount is from about 4% to about 12%.
The biodegradable polymers used in the invention are non-toxic, non-irritating, easily spreadable, and form a film of herbal actives to provide protection to wounds from air and water for about 1 to about 4 hours, more preferably from about 2 to about 3 hours and provide sustained release effect. The most preferred biodegradable polymer for polyherbal would healing film forming spray composition are the acrylate copolymers such as Eudragit RL® or RS® or ethylcellulose.
The biodegradable polymer is capable of forming a film or a barrier on the over wounds against external environment (air and water contaminations) ensuring an optimal healing environment while offering protection from extraneous materials. This film sustains bioactive release to wound site for about 1 to about 4 hours, which helps drug delivery to ensure therapeutic efficacy in its indent’s usage time.
In another embodiment, the polyherbal topical film forming spray composition which provides wound healing and /or wound protection for a period of about 1 hour to about 4 hours.
In another embodiment, the polyherbal topical film forming spray composition which provides sustained release of polyherbal bio-a actives for providing wound healing and /or wound protection for a period of about 1 hour to about 4 hours.
In some embodiment polyherbal topical film forming spray composition further comprises an effective amount of one or more antioxidants which prevents the initial degradation of active agent during the manufacturing process. The anti-oxidant may be selected from ascorbic acid, EDTA, trolamine, tocopherol, propyl galate, sodium sulfite and mixtures of any of the foregoing. The amount of antioxidant in the polyherbal wound healing film forming composition comprise is from about 0.25% to about 2%.
In some embodiment polyherbal topical film forming spray composition further comprises an effective amount one or more solvent. The solvent used for the polyherbal wound healing film forming composition includes ethanol, isopropyl alcohol, acetone, n-butanol, methylene chloride, methylene dimethyl ether, water, hydroalcoholic system alone and or in combination of two or more solvents. The solvent concentration in the topical spray formulation is between about 20% to about 80% and more preferably from about 30% to about 70%. Preferably, the solvent is an ethanol, acetone or isopropyl alcohol.
In some embodiments, polyherbal topical film forming spray composition further comprises of preservatives, to prevent microbial growth. Suitable preservatives for use in the present invention include, but are not limited to benzoic acid, boric acid, p-hydroxybenzoates, phenols, chlorinated phenolic compounds, alcohols, quarternary compounds, mercurials, mixtures of the foregoing and the like. The preservatives present in the polyherbal wound healing film forming composition range from about 0.01% to about 0.2% and most preferred from about 0.05% to about 0.15%.
In some embodiments, polyherbal topical film forming composition spray further comprises an effective amount of one or more permeation enhancers which allows a sufficient amount of the dose of the polyherbal active to permeate through the skin. Preferred permeation enhancers include isopropyl myristate, Oleic acid, Capric acid, Laurie acid, Laurie acid, pharmaceutically acceptable glycol derivatives (e.g., propylene glycol, diethylene glycol monoethyl ether), methyloleate, lysophosphatidylcholine, phosphatidylcholine, aprotinin, azone, cyclodextrin, dextran sulfate, menthol, 12 polysorbate 80, sulfoxides and various alkyl glycosides, urea, ethanol, caprylic alcohol, oleyl alcohol, n-methyl-2-pyrrolidone, sodium lauryl sulfate, isostearic acid, oleth-2, polyethylene glycol, polyoxyl cetostearyl ether, polyoxyl oleyl ether, polyoxyl lauryl ether, polyoxyl stearyl ether, benzyl alcohol, mixtures of any of the foregoing, and the like. In certain preferred embodiments, the permeation enhancer is selected from isopropyl myristate, oleth-2, oleic acid, 2-pyrolidone, isostearic acid, oleyly alcohol, polysorbate 80, polyethylene glycol 600, and mixtures of any of the foregoing. The amount of permeation enhancer in the composition can range from about 0.5% to about 25%. In certain preferred embodiments, the film forming topical spray formulation comprises from about 1% to about 10% by weight permeation enhancer(s), and in certain embodiments most preferably from about 2.5% to about 8% permeation enhancer.
In some embodiments, polyherbal topical film forming spray composition further comprises an effective amount of one or more fragrance ingredients. The fragrance ingredient which can be present in the invention are Lemon grass oil, Lavender oil tea tree oil, sandalwood oil and the like and comprise about 0.1% to about 1%.
In some embodiments, the polyherbal topical film forming spray composition further comprise of an effective amount of plasticizer to maintains elasticity and prevents cracking of the film selected from triethyl citrate, dimethyl isosorbide, acetyltributyl citrate, castor oil, propylene glycol, and polyethylene glycol, or any two or more of the above in combination. The amount of permeation enhancer in the composition can range from about 0.5% to about 3%.
In some embodiments, the polyherbal topical film forming spray composition, comprises crosslinkers affect the elasticity, viscosity, solubility, glass transition, and film stiffness of the polymer. The use of NaCl as a crosslinker in gellan gum also affects the gel’s sensitivity to temperature, so that film formation is better and faster. NaCl also increases cell encapsulation in gellan gum. The amount of crosslinkers in the composition can range from about 1 % to about 5%.
In some embodiments, the polyherbal topical film forming spray composition comprises propellants present in the polyherbal composition should be sustainable, disperse or release the entire composition from the can without losing the dose and should be compatible with all other substances. Propellants can be selected from hydrocarbons (eg. propane, butane, isobutane), Hydrochlorofluorocarbons and hydrofluorocarbons, Inert gases (eg. nitrogen, NO2, CO2) and combination thereof. The most preferred Propellants present in polyherbal film forming composition is mixture of Propane, n-butane and butane. The amount of propellant in the composition can range from about 10% to about 80%. In certain preferred embodiments, the film forming topical spray formulation comprises from about 30% to about 60%.
Yet another embodiment, the polyherbal topical film forming spray composition provides wound healing such as wound protection, pain reduction and scar removal in burns and wounds, physical wounds, ischaemic wounds, diabetic wound, pressure wounds including acute and chronic wounds.
Yet another embodiment, the polyherbal film forming topical composition is for topical application in or on a diabetic wound and /or pressure wound that is believed to promote healing and tissue growth, wound protection, provide nutritional factors and antioxidants, and to eradicate infection and accelerate wound healing. It provides the benefit of anti-inflammatory, antifungal and antimicrobial and analgesic properties from plant bio-actives.
Yet another embodiment is to provide a polyherbal topical film forming spray composition comprising about 0.5% to about 5% Nano Curcumin, about 1% to about 5% turmerones, about 0.5% to about 5% quercetin, about 0.0.01% to about 3% of Asiaticosides, about 0.1% to about 3% of clove oil, about 4% to about 12% of one or more biodegradable polymer, about 0.25% to about 2.5% of plasticizer, about 30% to about 60% of one or more propellant, and about 20% to about 80% of solvent.
Yet another embodiment provides a method of preparing polyherbal wound healing film forming spray composition for application to the skin of the subject comprising.
(i) dissolving biodegradable polymer in solvent in a closed vessel and divide into two parts;
(ii) mixing Turmerones and Nano curcumin until clear solution formed;
(iii) adding quercetin to step (ii);
(iv) adding clove oil to a portion of step (i);
(v) Mixing step (i) second portion with step (ii) in a closed vessel to make uniform solution, followed by step (iv) second part of solution;
(vi) Storing the solution of step(v) in closed holding tank to allow the solution to mature. This allows the plant bio-actives to dissolve naturally and get embedded in the polymer; and
(vii) Adding Step (vi) solution to closed filling tank and filling into aluminium cans followed by propellant addition and sealing the cans.
The compositions are preferably in a form suitable for application by spraying from an aerosol or pump spray container. Preferably round aluminium aerosol cans are used for composition filling. Full cone nozzles or hollow cone nozzles are used in the aerosol spray.
The polyherbal film forming topical spray of the present invention is preferably sprayed as micro droplets and nan droplets onto the wound of the subject. Once the solvent evaporates, the polyherbal film is formed on the wound and sets as a stable, highly nano- or micro-porous, non-irritating, non-toxic film. The film so formed on the surface of wound acts to cause wound healing, wound protection and provides a sustained effect of the plant bio-actives thereby providing a wound healing effect. The polyherbal film forming spray composition is sprayed to the skin as a liquid and forms an almost invisible film in situ by volatile solvent evaporation. The film is peel able and/or non-peel able in nature. The film is microporous. The film is breathable, meaning that it does not interfere with perspiration, respiration and other metabolic activities of the skin. The film is preferably non-greasy and non-sticky.
Yet another embodiment provides polyherbal topical film forming spray composition comprising Nano Curcumin, Turmerones, Quercetin, Centella asactica extract, clove oil wherein the polyherbal film forming spray composition provides comparable wound contraction compared to standard, when soframycin ointment was used as standard.
Other embodiments of the present disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the disclosed embodiments. The following examples should be considered as exemplary only.
Experimental Details:
The following examples in accordance with the present invention are not to be construed as limiting the present invention in any manner and are only samples of the various formulations described herein.
Example 1
S. NO Ingredient %
1 Eudragit RLPO 6.000
2 Ethyl Cellulose 2.500
3 Turmerones 30-40% 2.000
4 Nano curcumin 20-50% 1.000
5 quercetin 95% 0.500
6 Asiaticosides 40-50% 0.500
7 Tea tree oil 1.000
8 Fragrance 0.250
9 Camphor 0.250
10 Menthol 0.500
11 PEG 400 1.000
12 Clove oil 0.500
13 Acetone 25.000
14 IPA/Ethanol 55.000
15 Propanol q.s.
Example 2
S. NO Ingredient %
1 Eudragit RLPO 10
2 Ethyl Cellulose 1
3 Turmerones 30-40% 5
4 Nano curcumin 20-50% 1
5 quercetin 95% 3
6 Asiaticosides (40-50%) 1
7 Tea tree oil 0.5
8 Fragrance 0.25
9 Camphor 0.1
10 Menthol 0.3
11 PEG 400 0.25
12 Clove oil 0.5
13 Acetone qs
14 IPA/Ethanol qs
15 n-butane qs
Example 3
S. NO Ingredient %
1 Eudragit RS 100 6
2 Turmerones 30-40% 2
3 Nano curcumin 20-50% 4
4 quercetin 95% 2
5 Asiaticosides 40-50% 3
6 Tea tree oil 0.5
7 lavender oil 0.25
8 Camphor 0.5
9 Menthol 0.5
10 PEG 400 0.5
11 Clove oil 1
12 Acetone qs
13 IPA/Ethanol qs
14 I-butane q.s
Example 4
S. NO Ingredient %
1 Eudragit RS 100 10
2 Turmerones 30-40% 3
3 Nano curcumin 20-50% 2
4 quercetin 95% 1.5
5 Asiaticosides (40-50%) 3
6 Tea tree oil 0.5
7 Fragrance 0.25
8 Camphor 1
9 Clove oil 0.25
10 Acetone 25
11 IPA/Ethanol 59
12 Propane q.s
Example 5
S. NO Ingredient %
1 Eudragit RL/RLPO 9
2 Turmerones 30-40% 2.5
3 Nano curcumin 20-50% 2.5
4 quercetin 95% 3
5 Asiaticosides (40-50%) 0.075
6 Tea tree oil 1
7 Fragrance 0.125
8 Camphor 0.75
9 Clove oil 0.25
10 Acetone qs
11 IPA/Ethanol qs
12 Propane q.s.
Procedure:
1. Dissolved the biodegradable polymer in Ethanol, Acetone and/or IPA or mixture thereof by magnetic stirring till the polymer is completely soluble in a closed vessel;
2. Mixed Turmerones and Nano curcumin until clear solution formed;
3. Added quercetin to step no 2;
4. Added clove oil to a portion of step 1;
5. Mixed step 1 second portion with step 2 in a closed vessel to make uniform solution, followed by step 4 second part of solution for 60-120 min;
6. Stored the above solution in closed holding tank and allow to mature solution which will allow the plant bio-active to dissolve naturally and get embedded in the polymer;
7. Step 6 is added to closed filling tank and fill into aluminium cans followed by propellant addition and seal the cans; and
8. Labelled the aluminium cans having medicament.
Evaluation:
Appearance and pH
The spray formulation appeared yellow to brown colour solution. The spray of the formulation on the glass slide appeared as yellow film. pH of the spray was measured by pH meter and was adjusted to 6-7 by adding 0.1 N HCl drop wise.
Spray pattern
The spray pattern of the formulations was assessed by delivering the spray through the spray bottle on to the Whatman filter paper at a distance of 5 cm. The formulation exhibited good spray pattern in terms of uniformity and full cone shape of the spray area with absence of stray droplets.
Stickiness
The stickiness of the spray was tested by spraying the formulation onto the glass slide and pressing the cotton wool on the film formed on the glass slide. Based on the stickiness of the film, cotton fibres may retain on the glass slide.
The sprays were found to be non-sticky with no adherence of cotton fibres on the film or the glass slide upon which the film was formed.
Specific gravity
Specific gravity of the samples was analysed and was found to be 0.75-1.05.
Analysis:
a) Analysis of heavy metal, mycotoxins, pesticides residues:
The spray composition was analysed for heavy metal detection like lead, arsenic, cadmium, Mercury, and also for mycotoxins and pesticides residues. All the values are meeting quality parameters.
b) Assay
The amount of drug present in the formulations was assessed using different analytical methods. The amount of curcuminoids was analysed by UV method. The amount of curcuminoids present in the formulations was found to be 1.707% ppm. The amount of quercetin was analysed by HPLC method. The amount of quercetin present in the formulations was found to be 0.180% ppm. The amount of Asiaticosides was analysed by HPLC method. The amount of Asiaticosides present in the formulations was found to be 0.55% ppm.
Stability:
The prepared spray solutions were subjected to stability studies as per the ICH guidelines in stability chamber at 25°C±2°C (long term), 30°C ±2°C(intermediate), 40°C ±2°C (accelerated) and 60% ±5% relative humidity for 6 months. The samples were assessed for assay and for physical appearance at the sample points of 1, 3 and 6 months and were found to be stable as given in table 1 to table 3.
Table 1: Long term stability testing
S. No. Parameter Specification Initial 3 M 6 M
1. Description Yellow to brown Coloured solution Complies Complies Complies
2. pH 6-7 6.55 6.8 6.7
3. Assay Content in Percentage 90.00 to 110.00 % w/w
1. Turmerones 95% 1.5% 100.12 NA 100.52
2.Quercetin 95% 0.25% 98.9 NA 100.45
3. Asiaticosides 40%: 0.5% 99.75 NA 100.14
Microbial Tests
Total Aerobic Microbial Count (CFU/gm/ml) Not more than 3000cfu/g Less than 10 NA NA
Total Yeast and Mould Count (CFU/gm/ml) Not more than 100cfu/g Less than 10 NA NA
Coliforms Negative / 10g Absent NA NA
Pathogens Detection
E.Coli/gm Negative / 10g Absent NA NA
Salmonella spp./gm Negative / 10g Absent NA NA
P.Aeruginosa/gm Negative / 10g Absent NA NA
Staphylococcus Aureus/gm Negative / 10g Absent NA NA
Table.2: Intermediate Stability testing
S. No. Parameter Specification Initial 3 M 6 M
1. Description Yellow to brown Coloured solution Complies Complies Complies
2. pH 6-7 6.55 6.8 6.5
3. Assay Content in Percentage 90.00 to 110.00 % w/w
1. Turmerones 95% 1.5% 100.12 NA 99.65
2.Quercetin 95% 0.25% 98.9 NA 98.79
3. Asiaticosides 40%: 0.5% 99.75 NA 99.45
Microbial Tests
Total Aerobic Microbial Count (CFU/gm/ml) Not more than 3000cfu/g Less than 10 NA NA
Total Yeast and Mould Count (CFU/gm/ml) Not more than 100cfu/g Less than 10 NA NA
Coliforms Negative / 10g Absent NA NA
Pathogens Detection
E.Coli/gm Negative / 10g Absent NA NA
Salmonella spp./gm Negative / 10g Absent NA NA
P.Aeruginosa/gm Negative / 10g Absent NA NA
Staphylococcus Aureus/gm Negative / 10g Absent NA NA
Table 3. Accelerated stability testing
S. No. Parameter Specification Initial 1 M 3 M 6 M
1. Description Yellow to brown Coloured solution Complies Complies Complies Complies
2. pH 6-7 6.5 6.55 6.45 6.52
3. Assay Content in percentage 90.00 to 110.00 % w/w
1. Turmerones 95% 1.5% 99.5 100.12 101.25 98.5
2.Quercetin 95% 0.25% 98.9 98.9 100.05 99.12
3. Asiaticosides 40%: 0.5% 100.2 99.75 99.89 100.3
4. Microbial Tests
Total Aerobic Microbial Count Not more than 3000cfu/g Less than 10 NA NA Less than 10
Total Yeast and Mould Count Not more than 100cfu/g Less than 10 NA NA Less than 10
Coliforms Negative / 10g Absent NA NA Absent
Pathogens Detection
E. Coli/gm Negative / 10g Absent NA NA Absent
Salmonella spp./gm Negative / 10g Absent NA NA Absent
P. Aeruginosa/gm Negative / 10g Absent NA NA Absent
Staphylococcus Aureus/gm Negative / 10g Absent NA NA Absent
Procedure Diffusion study:
In vitro skin permeation studies were carried out using Franz diffusion cell with a receptor compartment capacity of 20 mL. Excised chicken intestine collected from an abattoir was cleaned and mounted between the donor and receptor compartments of the diffusion cell. The formulation was placed over the skin and covered with paraffin film. The receptor compartment of the diffusion cell was filled with a phosphate buffer of pH 7.4 contained 20% alcohol. The whole assembly was fixed on a magnetic stirrer. The solution in the receptor compartment was stirred continuously using a magnetic bead at 50 rpm, with the temperature maintained at 32 ± 0.5°C. The samples were withdrawn at different time intervals and analysed for drug content using a UV–Vis spectrophotometer at 425 nm. The receptor phase was replenished with an equal volume of the same medium. The cumulative amount of drug permeated is calculated.
Table 4: Nano Curcumin without dispersing in Turmerone
S.NO TIME DRUG RELEASE (mg) % DRUG RELEASE
1 5 min 2.8 2.00
2 15 min 6.5 4.74
3 30 min 14.1 10.29
4 1 hr 23.2 16.93
5 2 hr 30.7 22.41
6 3 hr 42.9 31.31
7 4 hr 49.5 36.13
Table 5: Nano Curcumin dispersion with Turmerone
S.NO TIME DRUG RELEASE (mg) % DRUG RELEASE
1 5 min 4.1 2.99
2 15 min 10.8 7.88
3 30 min 21.4 15.62
4 1 hr 30.2 22.04
5 2 hr 45.1 32.91
6 3 hr 61.9 45.18
7 4 hr 89.5 65.33
The sustained release pattern of the spray formulation was observed as shown in fig 1 (1ml spray contain = 137mg curcumin. The drug nano curcumin was release in sustained manner over the period of 4 hrs as shown in table 5.
Skin irritation test:
The skin irritation test was performed to test the dermatological safety of spray composition. The study is conducted in 24 human volunteers for duration of 7 days. Product was evaluated through single application of closed patch test under occlusion for 24 hrs. After patch removal, skin was observed for irritation reactions at 0 hr, 24hr, 48hrs post patch removal for immediate reactions and 7 days post patch removal for delayed reactions.
The scoring on irritation was done on draize scale, where the results were graded from 0 to 4, where 0 indicates no erythema and no edema, 1 indicates very slightly erythema or edema, 2 indicates well-defined erythema or slight edema, 3 indicates moderate to
severe erythema or slight edema and 4 refer to severe erythema. The mean score for irritation was calculated using following formula:
Mean Score for Irritation = Total score (Erythema + Oedema) for each sample / Total no. of Subject
Table 6: Average mean skin irritation score for each tested formulation:
Sample Mean irritation score (0hr) Irritancy assessment Mean irritation score
(24 hrs) Irritancy assessment Mean irritation score
(48 hrs) Irritancy assessment Mean irritation score
7th Day Irritancy assessment
Spray formulation 0.00 Non-Irritant 0.00 Non-Irritant 0.00 Non-Irritant 0.00 Non-Irritant
Positive control 3.58 Mild irritant 2.62 Mild irritant 2.21 Mild irritant 0.00 Non-Irritant
Negative control 0.00 Non-Irritant 0.00 Non-Irritant 0.00 Non-Irritant 0.00 Non-Irritant
The test product emerged as non-irritant when observed at 0hr, 24 hours, 48 hours and 7 days post patch removal. Positive control (1% Sodium Lauryl Sulphate in distilled water) was confirmed as mild-irritant when observed at 0 hr, 24 hrs, 48 hrs and non-irritant at 7 days of post patch removal. Negative control (0.9% Isotonic Saline solution) was confirmed as non-irritant when observed at 0hr, 24 hours, 48 hours and 7 days post patch removal (Fig 2). The study concludes that the spray formulation passes the skin irritation test and found to be non-irritant.
Pharmacological evaluation:
Example 3 of the present invention was subjected to Animal study to assess the wound healing properties. The study was performed for evaluation of wound healing property of polyherbal film formation spray in excision wound model of Male Wistar Rats. The total number of 10 animals were divided in to groups containing (3M) per group. The study design is mentioned in Table 7 and experimental procedure in Table 8.
Table 7: Study Design
Sr.No Group Volume (no of sprays) No of animals
1 Control - 03
2 Test Formulation 2 04
3 Standard (Soframycin ointment) SOS (As needed) 03
Dose: The dosage for rats extrapolated using standard guidelines
Route: topical
Study Duration: 22 days
Administration of test items: 15 days
Duration of treatment: Thrice daily
Table 8: Experimental procedure
Group No of animals Animal No drug/vehicle Drug volume Wound closure readings & images were taken on Days Body weights were taken on Days
Control N=3 1,2,3 - - D0,D3,D5,D7,D9,D11,D13,D15 D0,D2,D4,D6,D8,D10,D12,D14
Test item N=4 4,5,6,7 Herbal formulation 2 sprays t.i.d D0,D3,D5,D7,D9,D11,D13,D15 D0,D2,D4,D6,D8,D10,D12,D14
Standard N=3 8,9,10 Soframycin ointment SOS t.i.d D0,D3,D5,D7,D9,D11,D13,D15 D0,D2,D4,D6,D8,D10,D12,D14
Experimental procedures: The Wound formation by excision wound rat model was selected to evaluate wound healing property of test item. Day before the surgery the back of rats were shaved. On day 0, Physical injury by excision wound of circular shape 15*15*15 mm was made on anesthetized rats of all groups using Isoflurane as anesthetic agent. Treatment of test item and standard were administered from Day1 thrice daily topical application. Time interval of 3 hrs was given between two consecutive doses. For every animal even for control group saline washings of wound was performed before dosing. All alternate days wound closure readings were taken. Photographic data of wounds were collected. Body weights of rats were recorded as grams. Terminal sacrifice was performed after completion of dosing regimen. On Day 16 rats were euthanized and skin samples of Escher formed area collected, stored in 10% formalin solution and evaluated for Histopathological findings by H & E staining.
The percentage wound contraction was calculated using the formula
% wound contraction = Initial wound reading-Day15 wound reading X 100
Initial wound reading
The percentage wound healing contraction for composition of example 3 is provided in Table 9.
Table 9: Percentage wound healing contraction
Groups % Wound contraction (Day 15)
Control 99.5
Test item 100
Standard 99.8
The skin samples were evaluated for Histological examination by H and E staining. The wound region and normal skin morphology were clearly noticed. Aligning to the other parameters the test item group animals have shown complete re-epithelization along with neo-vascularization. The formulation has shown promising efficacy in wound healing property.
As per the raw data compilation of parameters like Photographic visual representation and wound readings for the herbal formulation and Soframycin ointment administered topically, groups have showed significant wound healing effect. The data shows promising wound healing effects of herbal formulation at given strength and has shown more efficacy compared to control and standard groups. The Escher formation may be slightly delayed in test item group but overall wound closure is better in test item group compared to standard group.
The data shows promising wound healing effects of herbal formulation at given strength and has shown more efficacy compared to control and standard groups in male Wistar rats that received excision wound. The test item formulation has shown Neo vascularisation in the exposed wound area and resulted in 100% wound closure within 15 days. Also, the formulation has analgesic and anti-inflammatory properties that enhanced the re epithelization of damaged skin with increased collagen formation. ,CLAIMS:WE CLAIM:
1. A polyherbal topical film forming spray composition comprises nano curcumin, turmerones, quercetin, Asiaticosides, clove oil and a pharmaceutically acceptable pharmaceutical excipient.
2. The polyherbal topical film forming spray composition as claimed in claim 1, wherein a pharmaceutically acceptable excipient comprises biodegradable polymer, antioxidant, plasticizer, propellant, solvent, preservatives, permeation enhancers, fragrances, Crosslinkers or combination thereof.
3. The polyherbal topical film forming spray composition as claimed in claim 2, wherein biodegradable polymer are selected from acrylates copolymers particularly ammonio methacrylate copolymer type a and ammonio methacrylate copolymer type b, (Eudragit®, RL and RS), Cellulose derivatives such as hydropropyl methyl cellulose, ethylcellulose, carboxymethyl cellulose or hydroxy ethyl cellulose, polysaccharides, polyvinyl alcohol, polyethylene polypropylene, PVP, polyoxyethylene-polyoxypropylene block copolymer, carbomers, poloxamer, chitosan, gelatin, alginate, cyclodextrin derivatives, lactose, starch, cellulose, crosslinked polyacrylic acid polymers, xantham gum, pectin, polylactide, polycaprolactone, polyanhydrides, polyorthoesters, polyglycolides, polyethylene glycols, polyamides, polyurethanes, polyesteramides, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(amino acids), poly(methyl vinyl ether), and copolymers, terpolymers or combination thereof.
4. The polyherbal topical film forming spray composition as claimed in claim 2, wherein biodegradable polymer is selected from ammonio methacrylate copolymer type an and ammonio methacrylate copolymer type b or combination thereof.
5. The polyherbal topical film forming spray composition as claimed in claim 2, wherein antioxidants are selected from ascorbic acid, EDTA, trolamine, tocopherol, propyl galate, sodium sulfite and combination thereof.
6. The polyherbal topical film forming spray composition as claimed in claim 2, wherein plasticizer is selected from triethyl citrate, dimethyl isosorbide, acetyltributyl citrate, castor oil, propylene glycol, and polyethylene glycol and combination thereof.
7. The polyherbal topical film forming spray composition as claimed in claim 2, wherein propellants are selected from hydrocarbons such as propane, butane, isobutane, Hydrochlorofluorocarbons and hydrofluorocarbons, Inert gases such as nitrogen, NO2, CO2 and combination thereof.
8. The polyherbal topical film forming spray composition as claimed in claim 2, wherein solvents are selected from ethanol, isopropyl alcohol, acetone, n-butanol, methylene chloride, methylene dimethyl ether, water, hydroalcoholic and combination thereof.
9. The pharmaceutical acceptable excipient as claimed in claim 2, wherein preservatives are selected from benzoic acid, boric acid, p-hydroxybenzoates, phenols, chlorinated phenolic compounds, alcohols, quarternary compounds, mercurial and combination thereof.
10. The pharmaceutical acceptable excipient as claimed in claim 2, wherein permeation enhancers isopropyl myristate, oleth-2, oleic acid, 2-pyrolidone, isostearic acid, oleyly alcohol, polysorbate 80, polyethylene glycol 600, and combination thereof.
11. The pharmaceutical acceptable excipient as claimed in claim 2, wherein Fragrances are selected from camphor, Lemon grass oil, Lavender oil, tea tree oil, sandalwood oil, present in the range of 0.1% to about 1% by weight of total composition.
12. The polyherbal topical film forming spray composition as claimed in claim 1, comprises nano Curcumin in the range of 0.5% to 5%, turmerones in the range of 1% to 5%, quercetin in the range of 0.5% to 5%, Asiaticosides in the range of 0.0.01% to 3%, clove oil in the range of 0.1% to 3%, biodegradable polymer in the range of 4% to 12%, plasticizer in the range of 0.25% to 2.5%, antioxidant in the range of 0.25% to about 2%, propellant in the range of 30% to 60%, and solvent in the range of about 20% to 80%.
13. The polyherbal topical film forming spray composition as claimed in claim 1, further comprises Camphor, Menthol, honey, Aloe vera extract, Ocimum sanctum extract, Citrus lemon peel extract, Witch Hazel Liquid extract, chamomile extract, Jojoba oil, green tea extract and Pomegranate peel extract.
14. A method of preparing polyherbal topical film forming spray composition as claimed in claim 1 comprising:
(i) dissolving biodegradable polymer in solvent in a closed vessel and divide into two parts
(ii) mixing Turmerones and Nano curcumin until clear solution formed
(iii) adding quercetin to step (ii)
(iv) adding clove oil to a portion of step (i)
(v) Mixing step (i) second portion with step (ii) in a closed vessel to make uniform solution, followed by step (iv) second part of solution
(vi) Storing the solution of step(v) in closed holding tank to allow the solution to mature. This allows the plant bio-actives to dissolve naturally and get embedded in the polymer.
(vii) Adding Step (vi) solution to closed filling tank and filling into aluminium cans followed by propellant addition and sealing the cans.
15. A method of wound healing, comprising treating subject with a therapeutically effective amount of a pharmaceutical composition of claim 1, wherein the wounds are selected among an incised wound, a lacerated wound, a penetrating wound, a perforated wound, a puncture wound, an open wound, a subcutaneous wound, a closed wound, ischaemic wounds, diabetic wound, pressure wounds including acute and chronic wounds and a combination thereof.
16. A method of wound healing, comprising applying topically the pharmaceutical composition of claim 1 to a wound of a subject, wherein the pharmaceutical composition forms a film after application to protect the wound, to reduce the pain, to remove the scar and to improve wound healing.
| # | Name | Date |
|---|---|---|
| 1 | 202341074187-PROVISIONAL SPECIFICATION [31-10-2023(online)].pdf | 2023-10-31 |
| 2 | 202341074187-POWER OF AUTHORITY [31-10-2023(online)].pdf | 2023-10-31 |
| 3 | 202341074187-FORM FOR STARTUP [31-10-2023(online)].pdf | 2023-10-31 |
| 4 | 202341074187-FORM FOR SMALL ENTITY(FORM-28) [31-10-2023(online)].pdf | 2023-10-31 |
| 5 | 202341074187-FORM 1 [31-10-2023(online)].pdf | 2023-10-31 |
| 6 | 202341074187-EVIDENCE FOR REGISTRATION UNDER SSI(FORM-28) [31-10-2023(online)].pdf | 2023-10-31 |
| 7 | 202341074187-EVIDENCE FOR REGISTRATION UNDER SSI [31-10-2023(online)].pdf | 2023-10-31 |
| 8 | 202341074187-Proof of Right [06-11-2023(online)].pdf | 2023-11-06 |
| 9 | 202341074187-DRAWING [17-02-2024(online)].pdf | 2024-02-17 |
| 10 | 202341074187-CORRESPONDENCE-OTHERS [17-02-2024(online)].pdf | 2024-02-17 |
| 11 | 202341074187-COMPLETE SPECIFICATION [17-02-2024(online)].pdf | 2024-02-17 |
| 12 | 202341074187-STARTUP [02-03-2024(online)].pdf | 2024-03-02 |
| 13 | 202341074187-FORM28 [02-03-2024(online)].pdf | 2024-03-02 |
| 14 | 202341074187-FORM-9 [02-03-2024(online)].pdf | 2024-03-02 |
| 15 | 202341074187-FORM 18A [02-03-2024(online)].pdf | 2024-03-02 |
| 16 | 202341074187-FER.pdf | 2024-06-04 |
| 17 | 202341074187-OTHERS [25-09-2024(online)].pdf | 2024-09-25 |
| 18 | 202341074187-Form-4 u-r 12(5) [25-09-2024(online)].pdf | 2024-09-25 |
| 19 | 202341074187-FER_SER_REPLY [25-09-2024(online)].pdf | 2024-09-25 |
| 20 | 202341074187-CORRESPONDENCE [25-09-2024(online)].pdf | 2024-09-25 |
| 21 | 202341074187-CLAIMS [25-09-2024(online)].pdf | 2024-09-25 |
| 22 | 202341074187-FORM 3 [29-09-2024(online)].pdf | 2024-09-29 |
| 23 | 202341074187-US(14)-HearingNotice-(HearingDate-28-02-2025).pdf | 2025-01-30 |
| 24 | 202341074187-NBA Approval Submission [01-02-2025(online)].pdf | 2025-02-01 |
| 25 | 202341074187-PatentCertificate04-02-2025.pdf | 2025-02-04 |
| 26 | 202341074187-IntimationOfGrant04-02-2025.pdf | 2025-02-04 |
| 1 | searchE_03-06-2024.pdf |
| 2 | D1-D3E_03-06-2024.pdf |