A topical GEL composition comprising tea tree oil, peppermint oil, and aloe vera

Abstract

A TOPICAL GEL COMPOSITION COMPRISING TEA TREE OIL, PEPPERMINT OIL, AND ALOE VERA The present invention relates to a topical oral gel composition comprising tea tree oil, peppermint oil, and aloe vera extract, formulated for the prevention and treatment of peri-implantitis. While the individual therapeutic properties of these ingredients are known, their combined use in a single gel formulation targeting peri-implant pathogens has not been previously disclosed. The composition demonstrates synergistic antimicrobial activity, particularly against Porphyromonas gingivalis and Staphylococcus aureus, with efficacy comparable to 1% chlorhexidine gel. The invention also encompasses the process of preparation, stability profile, and therapeutic application of the gel as a safer, natural alternative for long-term oral care in peri-implantitis management.

Description

FIELD OF THE INVENTIONThe present invention is related to the field of pharmaceutical / herbal formulation technology that can be used in dentistry. More particularly, the present invention is directed to the pharmaceutical / herbal formulation in the form of an oral polyherbal gel composition for topical application, which comprises Tea tree oil, Peppermint oil, and Aloe Vera, its preparation, and its anti-microbial use against peri-implantitis pathogens.BACKGROUND OF THE INVENTIONPeri-implantitis is a polymicrobial infection around dental implants that causes inflammation of the peri-implant tissues leading to progressive damage of supporting bone, leading to implant loss. Prevalence of peri-implantitis varies from 11.3% to 47.1% [Perez-Chaparro PJ et al. The current weight of evidence of the microbiologic profile associated with peri-implantitis: A Systematic Review. J Periodontol. 2016; 87:1295-1304].Peri-implantitis is caused due to five gram negative anaerobes, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia which belong to the red complex and Prevotella intermedia, Camylobacter rectus to the orange complex, with Porphyromonas gingivalis and Prevotella intermedia being the most predominant and virulent organisms causing peri-implant bone loss [Norowski Jr PA et al. Biomaterial and antibiotic strategies for peri-implantitis: A review. Journal of biomedical materials research part B: Applied biomaterials: An official journal of the society for biomaterials, the Japanese society for biomaterials, and the Australian Society for biomaterials and the Korean Society for biomaterials. 2009; 88:530-543; Lafaurie GI et al. Microbiome and microbial biofilm profiles of peri-implantitis: A Systematic review. J Periodontol. 2017; 88:1066-1089].Many non-surgical and surgical methods have been used for the intervention of peri-implantitis. These include supra-gingival and sub-gingival scaling with carbon, titanium or plastic curettes, air powder abrasive polishing, lasers, local application of antibiotics like chlorhexidine, tetracycline etc. Citric acid or H2O2 application, photodynamic therapy, resective surgery with bone grafts and GTR membranes are used [Smeets R et al. Definition, etiology, prevention and treatment of peri-implantitis-a review. Head & face medicine. 2014;10:1:34].Recently, more attention has been directed towards the usage of herbal anti-microbial agents such as neem, tulsi, aloe vera, ginger, turmeric, chamomile, tea tree, peppermint, eucalyptus, orange peel extract etc. against various organisms such as P. gingivalis, P. intermedia, S. aureus etc. [Ruth Lourenco et al. The invaluable role of phytotherapeutic agents in the adjunctive treatment of periodontal disease: A review. International Journal of health sciences and research 2020; 9:180-189].Aloe vera is a medicinal plant with anti-inflammatory, anti-microbial, anti-diabetic and immune-boosting properties. Some compounds like anthraquinones and saponin present in Aloe vera gel have direct antibacterial activities while some other components, such as acemannan, have been considered to exert indirect bactericidal activity through stimulation of phagocytosis. Studies have demonstrated the inhibitory activities of Aloe vera gel on some cariogenic (Streptococcus mutans) and periodontopathogen (Aggregatibacter actinomycetemcomitans, P. gingivalis) [Fani M et al. Inhibitory activity of Aloe vera gel on some clinically isolated cariogenic and periodontopathic bacteria. J Oral Sci. 2012;54(1):15-21].Essential oils have shown an antimicrobial efficacy against oral pathogens. Among the essential oils, Australian tea tree oil, peppermint oil, and sage oil have shown to inhibit the growth of obligate anaerobes and capnophilic microaerophiles at concentrations <0.6% [Park CM et al. Antimicrobial activity of essential oil against oral strain. International Journal of Clinical Preventive Dentistry. 2018;14(4):216-21]. From the above-mentioned three essential oils, research has shown some evidence of synergistic activity between peppermint oil combined with Australian tea tree oil and sage oil combined with eugenol; however, extensive studies are not conducted to establish the synergistic effect of the combination of these essential oils. Hence, further studies are necessary to validate the synergistic efficacy of these agents against peri-implant pathogens. [Shapiro S et al. The antimicrobial activity of essential oils and essential oil components towards oral bacteria. Oral Microbiol Immunol. 1994;9(4):202-8]. Therefore, in the present invention, the inventors preliminarily investigated the synergistic impact of the combination of peppermint and Australian tea tree oil, as opposed to the individual oils, against peri-implant pathogens at varying concentrations before formulating the herbal gel. The observed synergistic interaction between the essential oils supports the conclusion that the herbal formulation comprising said combination likewise exhibits synergistic effect.While previous studies have documented the individual use of tea tree oil, peppermint oil, and aloe vera in various skin care compositions, oral compositions and other applications, none of the prior research has documented the use of tea tree oil, peppermint oil, and aloe vera together as a combination in a single composition, for example, as a gel composition against peri-implantitis pathogens. Furthermore, the gold standard in the treatment of peri-implantitis is 1% Chlorhexidine gel, however, authorities recommend it's usage for a minimal duration due to adverse effects, including brown pigmentation and mucosal pain. Therefore, there is an existing need to investigate herbal and plant-derived components that exhibit low or no adverse effects and substantial efficacy in the treatment of peri-implantitis. So, the inventors of the present invention conducted this research to compare the anti-microbial effect of herbal gel containing tea tree oil, peppermint oil and aloe vera in comparison with gold standard 1% chlorhexidine gel against P. gingivalis and S. aureus, so that it can be used in a gel form as a more advantageous, safe and superior substitute of commercially available chlorhexidine gel. To the best of the inventors' knowledge, no prior art discloses a gel composition comprising tea tree oil, peppermint oil, and aloe vera extract in combination for the treatment of peri-implantitis.OBJECTS OF THE INVENTIONLooking at the need existing for a more effective and more advantageous therapy for peri-implantitis, the primary object of the present invention is to provide an oral composition for topical application comprising tea tree oil, peppermint oil, and aloe vera in the form of a gel composition. The gel composition of the present invention is safe, non-toxic and can be used / applied easily. Further, the gel composition of the present invention is stable and considerably less expensive as compared to available therapies for peri-implantitis.A yet another object of the present invention is to provide a gel composition, which comprises tea tree oil, peppermint oil, and aloe vera extract as a therapeutic agent having anti-microbial properties. The composition of the present invention is safe and practical to use with little technical expertise and it does not produce any undesirable by-products and side effects.In a yet another object, the present invention provides a gel composition comprising a synergistic oil, which is a combination of tea tree oil, and peppermint oil showing synergistic anti-microbial effect.In a yet another object, the present invention provides a gel composition comprising a combination of a synergistic oil (i.e. tea tree oil + peppermint oil), and aloe vera.A yet another object of the present invention is to provide a gel composition comprising tea tree oil, peppermint oil, aloe vera and a pharmaceutically acceptable excipient selected from a group comprising of a gelling agent, emulsifiers, surfactant, solvents, preservatives, pH adjusting agent, a vehicle, and any combinations thereof.A yet another object of the present invention is to provide a gel composition comprising tea tree oil, peppermint oil, aloe vera and pharmaceutically acceptable excipients such as carbopol 934, Span 60 and Span 20, Tween 80, glycerine, methyl paraben or its salt, sodium benzoate, triethanolamine, and water.A yet another object of the present invention is to provide a gel composition of tea tree oil, peppermint oil, and aloe vera extract having a prolonged stability, for example, at least for two months when stored at room temperature.In a yet another object, the present invention provides process of preparing the gel composition of the present invention.In a yet another object, the present invention provides use of the gel composition of the present invention for the prevention and / or treatment of peri-implantitis.In a yet another object, the present invention also provides a method of treating and / or preventing peri-implantitis, which comprises administering / applying therapeutically effective amount of the gel composition of the present invention.A yet further object of the present invention is to assess the anti-microbial activity of the gel composition of the present invention.A yet another object of the present invention is to compare and evaluate the anti-microbial activity of the gel composition of the present invention with the chlorhexidine composition.STATEMENT OF THE INVENTIONThe present invention relates to an oral polyherbal gel composition for topical application comprising tea tree oil, peppermint oil, and aloe vera extract, formulated for the prevention and treatment of peri-implantitis. While the individual therapeutic properties of these ingredients are known, their combined use in a single gel formulation targeting peri-implant pathogens has not been previously disclosed. The invention demonstrates that the combination of tea tree oil and peppermint oil exhibits a synergistic antimicrobial effect, significantly enhancing efficacy against Porphyromonas gingivalis and Staphylococcus aureus compared to each oil alone. The formulated gel was evaluated against the gold standard 1% chlorhexidine gel and showed comparable antimicrobial activity, with added benefits of reduced cytotoxicity, prolonged efficacy, and absence of adverse effects such as staining or mucosal irritation. The invention also encompasses the process of preparation, stability profile, and potential application of the gel as a safer, natural alternative for long-term oral care in peri-implantitis management.SUMMARY OF THE INVENTIONThe present inventors have through their vigorous research efforts prepared a herbal gel composition comprising tea tree oil, peppermint oil, and aloe vera for oral applications as an anti-microbial agent for prevention or treatment of peri-implantitis. The gel composition of the present invention comprises therapeutically effective amounts / concentrations of tea tree oil, peppermint oil, and aloe vera. The gel composition of the present invention further comprises a pharmaceutically acceptable excipient selected from the group of a gelling agent, an emulsifier, a surfactant, a preservative, a pH adjusting agent, a solvent, a vehicle and any combinations thereof.The process of the preparation of a gel composition of the present invention typically comprises following steps:1. Preparation of aloe vera extract;2. Preparation of gelling solution;3. Mixing of tea tree oil, pepper mint oil, aloe vera extract, and other excipients with gelling solution to prepare the final herbal gel composition; and4. pH adjustment of the gel composition followed by volume make-up to desired batchsize.BRIEF DESCRIPTION OF THE DRAWINGSThe accompanying drawings, which are incorporated in and constitute a part of this disclosure, illustrate an exemplary embodiment and together with the description, explain the disclosed embodiments. In the figures, the left and rightmost digit(s) of a reference number identifies the figure in which the reference number first appears. The same numbers are used throughout the figures to reference like features and components. Some embodiments of the system and methods of an embodiment of the present subject matter are now described, by way of example only and concerning the accompanying figures, in which:Figure-1: The gel composition of the present invention.DETAILED DESCRIPTION OF THE INVENTIONAttention on natural extract has been increasing because of the adverse effect of existing drug, and it is no exception in the oral-health related area. Chlorhexidine is the leading antibiotic substance, but authorities recommend the use for a minimum duration due to various side effects such as mucosal pain and pigmentation [Scheie AA. Modes of action currently known chemical anti-plaque agents other than chlorhexidine. J Dent Res 1989;681609-16]. The functional plants are used in the form of secondary metabolite using various extraction methods, and one of them is the essential oil. The essential oil has the basic structure consisting of oxygen, hydrogen, and carbon. It contains ketone, oxides, aldehyde, ester, and alcohol components [Campos CA, Gerschenson LN, Flores SK. Development of edible films and coatings with antimicrobial activity. Food Bioprocess Technol. 2011;4:849-75; Lodhia MH, Bhatt KR, Thaker VS. Antibacterial activity of essential oils from palmarosa, evening primrose, lavender and tuberose. Indian J Pharm Sci 2009;71:134-6; Chae IG, Kim HJ ,Yu MH ,Kim HI, Lee IS. Antioxidant and anti-bacterial activity of commercially available herbs in Korean markets. J Korean Soc Food Sci Nutr 2010;39:1411-17; and Kazemzadeh R, Nikjou R, Rostamnegad M, NorouziH. Effect of lavender aromatherapy on menopause hot flushing: a cross- over randomized clinical trial. J Chin Med Assoc 2016;79:489-92].Essential oils have demonstrated the antimicrobial activities against P. gingivalis, with Tea tree oil exhibiting highest antimicrobial activity at 19.50 mm followed by carrot seed at 17.44 mm and cinnamon essential oil at 16.82 mm [Park CM, Yoon HS. Antimicrobial activity of essential oil against oral strain. International Journal of Clinical Preventive Dentistry. 2018;14(4):216-21]. Australian tea tree oil, peppermint oil, and sage oil are among the essentialoils that have demonstrated the ability to prevent the growth of obligate anaerobes and capnophilic microaerophiles at concentrations below 0.6% [Park CM, Yoon HS. Antimicrobial activity of essential oil against oral strain. International Journal of Clinical Preventive Dentistry. 2018;14(4):216-21]. From the above mentioned three essential oils, research has shown some evidence of synergistic activity between peppermint oil combined with Australian tea tree oil and sage oil combined with eugenol; however, further studies are necessary to validate the synergistic efficacy of these agents against peri-implant pathogens. [Shapiro S, Meier A, Guggenheim B. The antimicrobial activity of essential oils and essential oil components towards oral bacteria. Oral Microbiol Immunol. 1994;9(4):202-8].In the present invention, the inventors preliminarily assessed the efficiency of tea tree oil and peppermint oil against P. gingivalis and S. aureus at various concentrations prior to formulating the herbal gel of the present invention. The impact of the combination comprising tea tree oil and peppermint oil, was also studied. The preliminary findings showed that the combination of tea tree oil and peppermint oil had higher antibacterial activity than individual essential oils against both species. Furthermore, the combination of tea tree oil and peppermint oil demonstrated prolonged antimicrobial efficacy against organism S. aureus at a 48-hour interval, as compared to the independently assessed essential oils.Moreover, Aloe vera has shown to exhibit potent anti-inflammatory and antibacterial characteristics, rendering it a useful natural remedy for oral infections [Moghaddam AA, Radafshar G, Jahandideh Y, Kakaei N. Clinical evaluation of effects of local application of aloe vera gel as an adjunct to scaling and root planning in patients with chronic periodontitis. Journal of Dentistry. 2017;18(3):165]. It has proven efficacy against the two most predominant periimplantitis pathogens like Porphyromonas gingivalis, Prevotella Intermedia [Fani M, Kohanteb J. Inhibitory activity of Aloe vera gel on some clinically isolated cariogenic and periodontopathic bacteria. J Oral Sci. 2012;54(1):15-21; Mangaiyarkarasi SP, Manigandan T, Elumalai M, Cholan PK, Kaur RP. Benefits of Aloe vera in dentistry. J Pharm Bioallied Sci. 2015;7(1):S255-9]. Mohammed et al. [Mohammed AT, NadiaAftan AL, AL-Ghurabi BH. Assessment of Interleukin-ip and Myeloperoxidase Levels around Implants versus Natural Teeth with the Impact of Aloe Vera. International Journal of Science and Research. 2016;6(6):1701-1705] conducted a study that demonstrated the anti-inflammatory properties of aloe vera on peri-implant tissue. Aloe vera was found to inhibit the inflammatory process, as indicated by reduced myeloperoxidase levels, leukocyte adhesion, and pro-inflammatorycytokines, potentially attributable to the presence of sterols as anti-inflammatory agents and lupeol as a possible antiseptic component. Another explanation for this outcome is that Aloe vera reduces the number of neutrophils and inhibits the migration of polymorphonuclear leukocytes, as well as diminishes the chemical and alternative pathways of complement activity to inhibit the formation of O2 free radicals. Rokaya et al. [Rokaya D, Srimaneepong V, Wisitrasameewon W, Humagain M, Thunyakitpisal P. Peri-implantitis update: risk indicators, diagnosis, and treatment. European journal of dentistry. 2020;14(04):672-82] suggested that Aloe vera extract (Acemannan sponges) has shown the ability to promote bone growth in bone defects and could be utilized in the treatment of peri-implantitis.Therefore, the herbal gel of the present invention was formulated using aloe vera extract, and the combination of peppermint oil and Australian tea tree oil. The prepared gel was compared to the widely known gold standard for peri-implantitis, 1% chlorhexidine gel, to determine its effectiveness in the treatment of peri-implantitis.The results of the study conducted by the present inventors demonstrated that the formulated herbal gel incorporating Aloe vera (Aloe barbadensis miller) extract, tea tree oil and peppermint oil exhibited antimicrobial activity against organisms S. aureus and P. gingivalis. The evaluated zone of inhibition of titanium discs coated with the formulated herbal gel was comparable to that of gold standard 1% chlorhexidine gel.The present invention evaluated the antimicrobial activities against two strains, however, the herbal gel of the present invention may also be effective against other bacterial strains related with peri-implantitis.DefinitionsAs used throughout this specification, the word "may" be used in a permissive sense (i.e., meaning having the potential to), rather than the mandatory sense (i.e., meaning, must).The use of the terms "a" and "an" and "the" and similar referents in the context of describing the invention (especially in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.As used herein, the term "about" is synonymous with "approximately" and is used to provide flexibility to a numerical value or range endpoint by providing that a given value may be "a little above" or "a little below" the value stated. "About" can mean, for example, within 3 or more than 3 standard deviations. "About" can mean within a percentage range of a given value. For example, the range can be ±1 %, ±5%, ±10%, ±20%, ±30%, ±40% or ±50% of a given value. "About" can mean with an order of magnitude of a given value, for example, within 2fold, 3-fold, 4-fold or 5-fold of a value. However, it is to be understood that even when a numerical value is accompanied by the term "about" in this specification, that express support shall be provided at least for the exact numerical value as well as though the term "about" were not present.The term "compatible" as used herein refers to those added excipients or ingredients or additives those are not substantially antagonistic to the other excipients or ingredients or additives or pharmaceutically active ingredients.As used herein, "treatment" refers to ameliorating or reducing symptoms associated with a disease or condition. Treatment means any manner in which the symptoms of a condition, disorder or disease are ameliorated or otherwise beneficially altered. Hence, treatment encompasses prophylaxis, therapy and / or cure. Treatment also encompasses any pharmaceutical use of the compositions herein.As used herein, "treating" a subject having a disease or condition means that a composition or other product provided or described herein is administered to the subject to thereby effect treatment thereof.As used herein, amelioration of the symptoms of a particular disease or disorder by a treatment, such as by administration of a pharmaceutical composition or other therapeutic, refers to any lessening, whether permanent or temporary, lasting or transient, of the symptoms that can be attributed to or associated with administration of the composition or therapeutic.As used herein, "prevention" or "prophylaxis" refers to methods in which the risk of developing disease or condition is reduced. Prophylaxis includes reduction in the risk of developing a disease or condition and / or a prevention of worsening of symptoms or progression of a disease, or reduction in the risk of worsening of symptoms or progression of a disease.As used herein, an "effective amount" or a "therapeutically effective amount" of a compound or composition for treating a particular disease is an amount that is sufficient to ameliorate, or in some manner reduce symptoms to achieve the desired physiological effect. Such amount can be administered as a single dosage or can be administered according to a regimen, whereby it is effective. The effective amount is readily determined by one of skill in the art following routine procedures.As used herein, "disease" or "disorder" or "condition" refers to a pathological condition in an organism resulting from cause or condition including, but not limited to, infections, acquired conditions, genetic conditions, and characterized by identifiable symptoms.As used herein, "patient" or "subject" to be treated includes humans and or non-human animals, including mammals. Mammals include primates, such as humans, chimpanzees, gorillas and monkeys; domesticated animals, such as dogs, horses, cats, pigs, goats, cows; and rodents such as mice, rats, hamsters and gerbils.As used herein, "optional" or "optionally" means that the subsequently described event or circumstance does or does not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. For example, an optionally substituted group means that the group is un-substituted or is substituted.As used herein, "comprises", "comprising", "containing" and "having" and the like can have the meaning ascribed to them in patent law and can mean "includes", "including" and the like, and are generally interpreted to be open ended terms. The terms "consisting of" or "consists of" are closed terms, and include only the components, structures, steps, or the like specifically listed in conjunction with such terms, as well as that, which is in accordance 10 with patent law. "Consisting essentially of" or "consists essentially of" have the meaning generally ascribed to them by patent law. In particular, such terms are generally closed terms, with the exception of allowing inclusion of additional items, materials, components, steps, or elements, that do not materially affect the basic and novel characteristics or function of the item(s) used in connection therewith. For example, trace elements present in a composition, but not affecting the composition's nature or characteristics would be permissible if present under the "consisting essentially of" language, even though not expressly recited in a list of items following such terminology. When using an open-ended term, like "comprising" or "including"it is understood that direct support should be afforded also to "consisting essentially of" language as well as "consisting of" language as if stated explicitly and vice versa. In essence, use of one of these terms in the specification provides support for all of the others. The term "comprise / comprises / comprising" as used herein mean that other ingredients, steps, etc. are optionally present. When reference is made herein to a method comprising two or more defined steps, the steps can be carried in any order or simultaneously (except where the context excludes that possibility), and the method can include one or more steps which are carried out before any of the defined steps, between two of the defined steps, or after all of the defined steps (except where the context excludes that possibility).The term "pharmaceutically acceptable" as used herein refers to an ingredient having compatibility with the other ingredients of the formulation and not deleterious to the recipient thereof.The term "quantity sufficient" (q.s.) refers to the amount of a substance required to achieve a specific parameter. For example, when used in the context of a pH-adjusting agent, it means the agent is added in an amount necessary to reach the desired pH. While the quantity of the pH-adjusting agent may vary from batch to batch, the target pH of the formulation remains a fixed parameter. When the term "quantity sufficient" (q.s.) is used in the context of a vehicle (such as water), it indicates that the vehicle is added in an amount necessary to achieve the final desired batch volume.The expression "%w / w" as used herein, refers to the percent weight of an identified component based on the total weight of the liquid. The expression "%w / v" as used herein, refers to the percent weight of an identified component based on the total volume of the liquid. The expression "%v / v" as used herein, refers to the percentage volume of an identified component based on the total volume of the liquid.The term "synergistic oil," as used herein, refers to a combination of tea tree oil and peppermint oil that exhibits a synergistic antimicrobial effect-meaning the combined activity against microorganisms is greater than the effect of each oil individually and exceeds the sum of their individual effects (i.e., more than an additive effect).In the present invention, the terms "Tea Tree Oil" and "Australian Tea Tree Oil" are used interchangeably and refer to the same substance, which is chemically identical.The term "emulsion," as used herein, refers to a biphasic system consisting of two immiscible liquids, typically an oil phase and an aqueous phase, wherein one phase is dispersed as fine droplets within the other with the aid of one or more emulsifying agents. Emulsions may be classified as oil-in-water (O / W) or water-in-oil (W / O) depending on the nature of the continuous phase. In the context of the present invention, the emulsion comprises essential oils (tea tree oil and peppermint oil) dispersed within an aqueous phase containing aloe vera extract and other excipients, stabilized by surfactants and emulsifiers.The term "emulsion-gel," or "emulgel," as used herein, refers to a semi-solid dosage form that combines the properties of an emulsion and a gel. It is formed by incorporating an emulsion system into a gel matrix, typically using a gelling agent such as Carbopol 934. The resulting formulation exhibits enhanced stability, spreadability, and controlled release characteristics. In the present invention, the emulgel comprises a synergistic oil (tea tree oil and peppermint oil), aloe vera extract, and pharmaceutically acceptable excipients, embedded within a gel base to facilitate topical oral application and prolonged antimicrobial efficacy.While the present invention is described herein by way of examples using various embodiments and illustrative drawings, those skilled in the art will recognize that neither the invention is intended to be limited to the embodiments of the described drawings nor is it designed to represent the scale of the various components. Further, some components that may form a part of the present invention may not be illustrated with specific figures. Such omissions do not limit the embodiment outlined in any way. The drawings and detailed description thereof are not intended to restrict the invention to the form disclosed. On the contrary, the invention covers all the modifications, equivalents, and alternatives falling within the scope of the present invention as defined by the appended claims. The headings are used for organizational purposes only and are not meant to limit the scope of the description or the claims.Before explaining at least one embodiment of the invention in detail, it is to be understood that the present invention is not limited in its application to the details outlined in the following / foregoing description or exemplified by the examples. The invention is capable of other embodiments or being practiced or carried out in various ways. Also, it is to be understoodthat the phraseology and terminology employed herein is for description and should not be regarded as limiting.Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Besides, the descriptions, materials, methods and examples are illustrative only and not intended to be limiting. Methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention.The present invention relates to the development of a gel composition comprising tea tree oil, peppermint oil, and aloe vera extract and its dental application or use, for example, in the prevention or treating peri-implantitis. The invention also pertains to the process of preparing gel composition of the present invention.BEST MODE OF CARRYING OUT THE INVENTIONAntimicrobial testing of Tea tree oil, Peppermint oil and combination of Tea tree oil and Peppermint oil ("synergistic oil"):The antimicrobial efficacy of tea tree oil, peppermint oil, and their combination was evaluated against P. gingivalis (ATCC 33277) and S. aureus (ATCC 25923). The results of these tests are summarized in Table-1, Table-2, and Table-3 below.Table-1: Zone of Inhibition in millimetres (mm) of Tea tree oil, Peppermint oil and Synergistic oil (combination of Tea Tree oil and peppermint oil) against organism P. Gingivalis after 96 hours incubation at 37°C in anaerobic jarTable-2: Zone of Inhibition in millimetres (mm) of Tea tree oil, Peppermint oil and Synergistic oil (combination of tea tree oil and peppermint oil) against organism S. Aureus after 24 hours incubationTable-3: Zone of Inhibition in millimetres (mm) of Tea tree oil, Peppermint oil and Synergistic oil (combination of tea tree oil and peppermint oil) against organism S. Aureus after 48 hours incubationFrom the results, it is evident that the combination of tea tree oil and peppermint oil exhibits a synergistic effect-meaning their combined antimicrobial activity is greater than that of each oil individually and exceeds the sum of their individual effects (i.e., more than an additive effect).Preparation of the herbal gel of the present inventionTable-4: Materials required for formulation of tea tree oil, peppermint oil and aloe vera comprising herbal gel# Carbopol 934 was soaked in 25 mL of water, resulting in an approximate gelling solution weight of 25.5 g.* considering 25-25.5gm of gelling solution weight.Physical properties of the herbal gel of the present invention:Color Straw colored, translucent viscous gelPH about 6.0 to about 6.8Viscosity 1.861 cP ±1.9 (SD)Process of preparation:For the preparation of the gel formulation of the present invention, mature and fresh leaves of Aloe vera (Geographical origin: Belagavi, Karnataka, India; ICMR certified; Aloe barbadensis Miller; accession number RMRC-1599) were utilized. The leaves were thoroughly rinsed with fresh water, the thick epidermis was removed, they were sectioned into transverse pieces, and the straw-colored extract was collected in a sterile container.The Tea Tree Oil (Melaleuca alternifolia; Indian Pharmacopoeia grade; typically sourced from plantations in Queensland and New South Wales, Australia) used in the formulation was purchased from Cyrus Enterprises, India. The Peppermint Oil (Mentha X piperita; Indian Pharmacopoeia grade; commonly cultivated in Uttar Pradesh, India) used in the formulation was purchased from Plant Therapy, India. Certificates of Analysis provided by the respective suppliers confirmed compliance with all required tests for both essential oils.The present invention utilizes Carbopol 934 as the gelling agent. To prepare the gelling agent solution, weighed quantity of Carbopol 934 0.5% w / w (0.5 gms) was soaked in 25 mL water for 24 hours. Subsequently, about 5% w / w glycerin (5 gms) was added to the Carbopol solution with constant stirring using a propeller at 100 rpm for 10 minutes. To the above mixture, 0.01% w / w methyl paraben (or its salt) and 0.5% w / w sodium benzoate were added as preservatives.Then, weighted quantity of freshly prepared aloe vera extract (about 5% w / w, 5 gms), about 2.0% w / w tea tree oil (2 gms), and about 2.0% w / w peppermint oil (2 gms) were slowly incorporated into a mixture containing about 1% w / w sorbitan monolaurate (Span 20), about 2% w / w sorbitan monostearate (Span 60), and about 1% w / w polysorbate 80 (Tween 80) with constant stirring at 200 rpm for 30 minutes, until a homogeneous emulsion was formed.This emulsion mixture was then added to the Carbopol 934 mixture with constant stirring at 150 rpm for 30 minutes to obtain a uniform gel base (an emulsion-gel or emulgel). The pH of the gel mixture was adjusted to about 7.0 by adding few drops of triethanolamine, followed by stirring for 10 minutes. A homogeneous gel was obtained and stored at room temperature in an airtight container. Stability testing was conducted in a controlled chamber at 23°C ± 2°C and 65% ± 5% RH (relative humidity) for two months, and the gel was found to be stable.Microbial analysis:For the microbial analysis, a total of 40 sterile titanium discs (Grade IV, American Society for Testing and Materials Specification Number: B348) of dimension 10mm x 2mm were used. They were further sub-divided into 2 groups: Group A (Formulated herbal gel containing Tea tree oil, peppermint oil and aloe vera extract) and Group B (1% Chlorhexidine gel).The disk-diffusion agar method was used to test the effectiveness of the formulated gel of the present invention on S. aureus (ATCC Strain number 25923) and P. gingivalis (ATCC Strain number 33277). An agar plate was first streaked with bacteria; after drying of the inoculum, an 8mm diameter and 3mm depth well was punched with a sterile cork borer. After which, sterile titanium discs were placed. Each plate was divided into two groups: the experimental group, which comprised of titanium discs coated with prepared herbal gel of the present invention (Group A); and the positive control group, which consisted of titanium discs coated with 1% chlorhexidine gel (Group B). Each titanium disc was coated with the gel of the present invention and 1% chlorhexidine gel using a dipping method, in which the disc was immersed in the formulated gel for Group A and 1% chlorhexidine gel for Group B for 45-60 seconds.The standard strain of P. gingivalis was inoculated on brucella blood agar at 37°C for 72-96 hours using the anerobic jar and. S. aureus was inoculated on Sabouraud dextrose agar at 37°C for 24 hours (aerobic). The zone of inhibition was defined as an absence of bacterial colonies around the antimicrobial agent forming a clear zone. The zone of inhibition of each well wasmeasured in millimeters (mm) using the Hi-media scale. The results obtained were tabulated and were subjected to analysis using one way Anova and Mann Whitney U test, p < 0.05.Determination of Cytotoxicity of formulated herbal gel of the present invention:The MTT solution was prepared using 5 mg in 1 ml of Phosphate Buffer Saline (PBS - pH 7.4) and cytotoxicity assay was performed on mouse fibroblast strain L929 (Testing done in Dr. Prabhakar kore Basic Science Research Centre, Belagavi). In-vitro growth inhibition effect of formulated herbal gel was assessed by ELISA reader by determination of conversion of MTT into "Formazan blue" by living cells. The 50μl of 4000 cells / ml cell suspension were seeded into each well in a 96 wells micro titre plate and final volume was made up to 200 μl by adding Dulbecco's Modified Eagle Medium (DMEM, HiMedia AL231A). In this study, 10μl of gel of the present invention was added to respective wells containing 200μl of the medium. After 24 hours incubation at 37°C in a humidified atmosphere of 5% CO2, stock solution of MTT was added to each well (20μl, 5mg per ml in sterile PBS) for further 4 hours incubation. The supernatant was carefully removed without disturbing the precipitated Formazan crystals and 100μl of DMSO was added to dissolve the crystals formed. The optical density (OD) was measured at wavelength of 570nm by using LISA plus. The study was performed in triplicates. The result represents the mean of three readings. Results demonstrated that favourable cell viability was seen with the formulated herbal gel, with a 92.12% cell viability.Formula:Surviving cells (%) = Mean OD of test compound *100Mean OD at controlResults:Table-5 demonstrates Minimum Inhibitory Concentration and Minimum Bactericidal Concentration values (%) of tea tree oil, peppermint oil and combination thereof against S. aureus (ATCC Strain number 25923) and P. gingivalis (ATCC Strain number 33277). The dilutions of the essential oil tested using the two-fold serial dilution were 4.0%, 2.0%, 1.0%, 0.5%, 0.25%, 0.125%, 0.06%, 0.03%, and 0.015%. The percentage indicates the concentration of the oil following dilution of the 100% essential oil with Brain Heart Infusion (BHI) broth.Table-5: Comparison of Minimum Inhibitory Concentration values (MIC) and Minimum Bacterial Concentration values (MBC) (%) of essential oils on 2 different microorganisms.The minimum inhibitory concentration (MIC) of tea tree essential oil and peppermint essential oil against P. gingivalis was 0.5%, whereas the MIC of their combination was 0.25%. For S. aureus, the MIC of the combined essential oils was significantly lower (0.125%) compared to tea tree oil (0.25%) and peppermint oil (0.5%). The minimum bactericidal concentration (MBC) of the combined essential oils was 0.25% for S. aureus and 0.5% for P. gingivalis.These results clearly indicate that the combination of tea tree oil and peppermint oil exhibits a synergistic effect, where the combined antimicrobial activity is greater than the individual effects of each oil and exceeds the sum of their individual effects (i.e., more than an additive effect). Furthermore, the combination of tea tree oil and peppermint oil demonstrated prolonged antimicrobial efficacy against S. aureus at a 48-hour interval compared to the individually tested essential oils. In fact, the antimicrobial effect of the combination persisted for at least 48 hours longer than that of either oil alone.Table-6 presents the zone of inhibition obtained using the disc diffusion method to evaluate the antimicrobial efficacy of the formulated gel against P. gingivalis and S. aureus, measured using the HiMedia scale.Table-6: Zone of Inhibition in millimetres (mm) of 1% Chlorhexidine and formulated herbal gel against two different microorganisms*Mann-Whitney U test*Statistically significant p<0.01For P. gingivalis, the maximum zone of inhibition observed with 1% chlorhexidine gel (positive control) was 26 mm, while the 2% formulated herbal gel (experimental group) showed 19 mm. For S. aureus, the maximum zone of inhibition was 29 mm with 1% chlorhexidine gel and 20 mm with the formulated herbal gel.The mean zone of inhibition for P. gingivalis was 21.60 ± 3.185 mm with chlorhexidine gel and 16.40 ± 1.729 mm with the herbal gel. For S. aureus, the mean zone of inhibition was 27.35 ± 1.137 mm for chlorhexidine gel and 18.45 ± 1.099 mm for the herbal gel. In the agar disc diffusion assay, the 2% formulated herbal gel produced smaller zones of inhibition than the 1% chlorhexidine gel against both P. gingivalis and S. aureus (Mann-Whitney U, p < 0.01).It is important to note that the disc diffusion method tends to underestimate the antimicrobial activity of hydrophobic agents, such as essential oils incorporated into gel matrices. This limitation arises from restricted diffusion through agar and the viscosity of the gel, which can hinder uniform dispersion. Consequently, the observed zones of inhibition may not fully represent the true antimicrobial potency under practical conditions.Despite this, the MIC and MBC results, along with the prolonged 48-hour efficacy demonstrated by the combination of tea tree oil and peppermint oil, indicate meaningful antimicrobial activity and a synergistic effect that surpasses the individual and additive effects of these oils. These findings suggest that, while the formulated herbal gel did not outperform chlorhexidine in the disc diffusion assay, it offers sustained antimicrobial action and potential advantages for long-term application. The herbal gel of the present invention offers comparable antimicrobial efficacy to chlorhexidine gel, with the added benefits of reduced cytotoxicity, absence of staining, and improved patient compliance.Chlorhexidine gel, while widely used as an oral antimicrobial agent, is associated with several side effects, including altered taste perception, tooth and oral surface staining, increased tartar formation, and occasional oral irritation or mucosal peeling. In rare cases, it may trigger serious allergic reactions such as swelling, rash, or breathing difficulties, as noted by regulatory warnings.In contrast, the formulated herbal gel of the present invention, containing tea tree oil, peppermint oil, and Aloe vera, offers multiple benefits. These natural components exhibit broad-spectrum antimicrobial activity, anti-inflammatory properties, and soothing effects onoral tissues, while being free from alcohol and harsh chemicals. Studies have shown that tea tree oil and Aloe vera can significantly reduce plaque, gingivitis, and oral bacterial load, with efficacy comparable to chlorhexidine but without its staining or taste-altering drawbacks. Additionally, the herbal gel provides a refreshing sensation, supports gum health, and minimizes the risk of adverse reactions, making it a safer and more patient-friendly alternative for long-term use.The references described herein are incorporated by reference in their entirety to the extent necessary. If there is a difference in meaning between the incorporated terms and the terms disclosed herein, the meaning of the terms disclosed herein will control.References:1. Perez-Chaparro PJ, Duarte PM, Shibli JA, Montenegro S, Lacerda Heluy S, Figueiredo LC, Faveri M, Feres M. The current weight of evidence of the microbiologic profile associated with peri-implantitis: A Systematic Review. J Periodontol. 2016; 87:12951304.2. Norowski Jr PA, Bumgardner JD. Biomaterial and antibiotic strategies for peri-implantitis: A review. Journal of biomedical materials research part B: Applied biomaterials: An official journal of the society for biomaterials, the japanese society for biomaterials, and the Australian Society for biomaterials and the Korean Society for biomaterials. 2009; 88:530-543.3. Lafaurie GI, Sabogal MA, Castillo DM, Rincon MV, Gomez LA, Lesmes YA, Chambrone L. Microbiome and microbial biofilm profiles of peri-implantitis: A Systematic review. J Periodontol. 2017; 88:1066-1089.4. Smeets R, Henningsen A, Jung O, Heiland M, Hammacher C, Stein JM. Definition, etiology, prevention and treatment of peri-implantitis-a review. Head & face medicine. 2014;10:1:34.5. Ruth Lourenco, James Samuel, Lois James Samuel. The invaluable role of phytotherapeutic agents in the adjunctive treatment of periodontal disease: A review. International Journal of health sciences and research 2020; 9:180-189.6. Fani M, Kohanteb J. Inhibitory activity of Aloe vera gel on some clinically isolated cariogenic and periodontopathic bacteria. J Oral Sci. 2012;54(1):15-217. Park CM, Yoon HS. Antimicrobial activity of essential oil against oral strain. International Journal of Clinical Preventive Dentistry. 2018;14(4):216-21.8. Shapiro S, Meier A, Guggenheim B. The antimicrobial activity of essential oils and essential oil components towards oral bacteria. Oral Microbiol Immunol. 1994;9(4):202-8.9. Scheie AA. Modes of action currently known chemical anti-plaque agents other than chlorhexidine. J Dent Res 1989;681609-16.10. Campos CA, Gerschenson LN, Flores SK. Developmentofedi- ble films and coatings with antimicrobial activity. Food Bioprocess Technol. 2011;4:849-75.11. Lodhia MH, Bhatt KR, Thaker VS. Antibacterial activity of essential oils from palmarosa, evening primrose, lavender and tuberose. Indian J Pharm Sci 2009;71:134-6.12. Chae IG, Kim HJ ,Yu MH ,Kim HI, Lee IS. Antioxidant and anti-bacterial activity of commercially available herbs in Korean markets. J Korean Soc Food Sci Nutr 2010;39:1411-17.13. Kazemzadeh R, Nikjou R, Rostamnegad M, NorouziH. Effect of lavender aromatherapy on menopause hot flushing: a cross- over randomized clinical trial. J Chin Med Assoc 2016;79:489-92.Abbreviations used in the present invention:P. gingivalis - Porphyromonous gingivalisS. aureus - Staphylococcus aureusMIC - Minimum Inhibitory ConcentrationMBC - Minimum Bactericidal ConcentrationBHI - Brain Heart InfusionELISA - Enzyme Linked ImmunoassayMTT - 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromideDMSO - DimethylsulfoxideATCC - American Type Culture CollectionRMRC - Regional Medical Research CentreRPM - Rounds Per MinutecP - CentipoisePBS - Phosphate Buffer SalineOD - Optical Densitymm - Millimetresgms - GramsMin - MinimumMax - MaximumSD - Standard DeviationCI - Confidence IntervalStd - StandardChx - Chlorhexidine

Claims

1. An oral composition in the form of a gel formulation for topical application comprising: about 2.0% w / w tea tree oil; about 2.0% w / w peppermint oil; about 5.0% w / w aloe vera; and a pharmaceutically acceptable excipient selected from a gelling agent, an emulsifier, a surfactant, a solvent, a preservative, a pH adjusting agent, a vehicle, and a combination thereof.

2. The composition as claimed in claim 1, wherein the aloe vera is in the form of extract prepared from aloe vera leaves.

3. The composition as claimed in claim 1, wherein the pH of the composition is about 7.0.

4. The composition as claimed in claim 1, wherein the composition is in the form of an emulsion-gel or emulgel.

5. The composition as claimed in claim 4, wherein the emulsion comprises an aqueous phase and an oily phase.

6. The composition as claimed in claim 1, wherein the gelling agent is carbopol 934 (cross-linked polyacrylic acid polymer) present in an amount of about 0.5% w / w; the emulsifier is sorbitan monostearate present in an amount of about 2.0% w / w and sorbitan monolaurate present in an amount of about 1.0% w / w; the surfactant is polysorbate 80 present in an amount of about 1.0% w / w; the solvent is glycerin present in an amount of about 5.0% w / w; the preservative is methyl paraben or its salt present in an amount of about 0.01% w / w and sodium benzoate present in an amount of about 0.5% w / w; the pH adjusting agent is triethanolamine in a quantity sufficient to adjust the pH of the composition to about 7.0; and the vehicle is water.

7. The composition as claimed in claims 1-6, wherein the composition per 100gm comprises: about 2gm tea tree oil; about 2gm peppermint oil; about 5gm aloe vera; about 0.5gm carbopol 934; about 2gm sorbitan monostearate; about 1gm sorbitan monolaurate; about 1gm polysorbate 80; about 5gm glycerine; about 0.01gm methyl paraben or its salt; about 0.5gm sodium benzoate; triethanolamine in a quantity sufficient to adjust the pH of the composition to about 7.0; and water.

8. An oral composition in the form of a gel formulation for topical application comprising: about 2.0% w / w tea tree oil; about 2.0% w / w peppermint oil; about 5.0% w / w aloe vera; about 0.5% w / w carbopol 934 (cross-linked polyacrylic acid polymer); about 2.0% w / w sorbitan monostearate; about 1.0% w / w sorbitan monolaurate; about 1.0% polysorbate 80; about 5.0% w / w glycerin; about 0.01% w / w methyl paraben or its salt; about 0.5% w / w sodium benzoate; triethanolamine in a quantity sufficient to adjust the pH of the composition to about 7.0; and water.

9. The process for the preparation of the composition as claimed in claim 8, wherein the process comprises: (a) Carbopol 934 was soaked in sufficient quantity of water for 24 hours; (b) Glycerin, methyl paraben or its salt, and sodium benzoate were added to the carbopol solution of step (a) to form gelling solution; (c) Aloe vera extract, tea tree oil, and peppermint oil were mixed with sorbitan monolaurate, sorbitan monostearate, and polysorbate 80 to form an emulsion; (d) Addition of emulsion of step (c) to gelling solution of step (b) to form an emulsion-gel; (e) Adjustment of the pH of the gel composition of step (d) with triethanolamine to about 7.0; and (f) Final volume make up with water.

10. Use of the composition as claimed in claim 1 or claim 8 against peri-implantitis pathogens.