Synergistic dentifrice (ORAL) composition, formulation and preparation method and application thereof

Abstract

Synergistic dentifrice (oral) composition, formulation and preparation method and application thereof. The present invention provides a synergistic dentifrice composition designed to promote healing of wounds at the dentin-pulp complex, and to prevent and treat oral conditions including leukoplakia, lichen planus, submucous fibrosis, erythroplakia, periodontal disease, dental caries, dentinal hypersensitivity, and ulcers. Additionally, the composition promotes remineralization, inhibits demineralization, and addresses xerostomia. The formulation includes Arginine hydrochloride, sodium fluoride (NaF) solution, Potassium Nitrate, Nano Hydroxyapatite, Curcuma Longa extract, zinc salts, and optionally a peptide with a length of 7 to 30 amino acid residues along with inactive ingredients.

Description

[0001]“SYNERGISTIC DENTIFRICE(ORAL) COMPOSITION, FORMULATION AND PREPARATION METHOD AND APPLICATION THEREOF” Field of Invention: The present invention relates to synergistic oral care (dentifrice) compositions comprising Arginine hydrochloride, sodium fluoride solution, Potassium Nitrate, Hydroxyapatite, Curcuma Longa extract, zinc citrate, and optionally a peptide(s) with a length of 7 to 30 amino acid residues along with inactive ingredients as a medicament for treating and managing oral conditions. Definitions: The term “dentifrice composition”, as used herein, includes tooth or subgingival paste, gel, or liquid formulations unless otherwise specified. The dentifrice composition may be a single- phase composition or may be a combination of two or more separate dentifrice compositions. The dentifrice composition may be in any desired form, such as deep striped, surface striped, multilayered, having a gel surrounding a paste, or any combination thereof. Each dentifrice composition in a dentifrice comprising two or more separate dentifrice compositions may be contained in a physically separated compartment of a dispenser and dispensed side- by-side. The term “dentifrice composition and formulation" as is used herein shall include a suitable vehicle, which can be used to apply the present compositions to the oral cavity in a safe and effective manner. Such vehicle may include, but is not limited to, materials such as fluoride ion sources, additional anticalculus agents, buffers, pH adjuster, other abrasive materials, peroxide sources, alkali metal bicarbonate salts, thickening materials, humectants, water, surfactants, herbal extract (s), flavor system, sweetening agents, xylitol, coloring agents, and mixtures thereof. “Active and other ingredients” useful herein may be categorized or described herein by their cosmetic and / or therapeutic benefit or their postulated mode of action or function. However, it is to be understood that the active and other ingredients useful herein can, in some instances, provide more than one cosmetic and / or therapeutic benefit or function or operate via more than one mode of action. Therefore, classifications herein are made for the sake of convenience and are not intended to limit an ingredient to the particularly stated function(s) or activities listed. The term "orally acceptable carrier" comprises one or more compatible solid or liquid excipients or diluents which are suitable for topical oral administration. By "compatible," as used herein, is meant that the components of the composition are capable of being commingled without interaction in a manner which would substantially reduce the composition’s stability and / or efficacy. The carriers or excipients of the present invention can include the usual and conventional components of mouthwashes or mouth rinses, as more fully described hereinafter: Mouthwash or mouth rinse carrier materials typically include, but are not limited to one or more of water, alcohol, humectants, surfactants, and acceptance improving agents, such as flavoring, sweetening, coloring and / or cooling agents While compositions and methods are described herein in terms of “comprising” various components or steps, the compositions and methods can also“consist essentially of or “consist of’ the various components or steps, unless stated otherwise. Several types of ranges are disclosed in the present invention. When a range of any type is disclosed or claimed, the intent is to disclose or claim individually each possible number that such a range could reasonably encompass, including end points of the range as well as any sub-ranges and combinations of sub-ranges encompassed therein. The term “about” means that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but can be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement errors, and the like, and other factors known to those of skill in the art. In general, an amount, size, formulation, parameter or other quantity or characteristic is “about” or “approximate” whether or not expressly stated to be such. The term “about” also encompasses amounts that differ due to different equilibrium conditions for a composition resulting from a particular initial mixture. Whether or not modified by the term “about,” the claims include equivalents to the quantities. The term “about” can mean within 10% of the reported numerical value, preferably within 5% of the reported numerical value. The dentifrices or articles are intended for use against erosive oral leukoplakia, oral lichen planus, oral submocous fibrosis, erythroplakia, periodontal disease and dental caries, dentinal hypersensitivity, ulcers, promoting remineralization and inhibiting demineralization, Xerostomia conditions of the mouth. For this purpose they are suitably provided as a kit containing the composition and human-readable indications disclosing to the subject using the composition that the composition is for use, or efficacious, against oral leukoplakia, oral lichen planus, oral submocous fibrosis, erythroplakia, periodontal disease and dental caries, dentinal hypersensitivity, ulcers, promoting remineralization and inhibiting demineralization, Xerostomia conditions of the mouth. These indications may be directly printed on the container comprising the dentifrice (such as a toothpaste tube), or they may be printed on a label wrapped or adhered onto the container. They may also be printed on a package, such as a cardboard box, enclosing the container. Finally they may be printed on a leaflet (a package insert), to be included into the kit. The dentifrice composition can be in any suitable form, such as a solid, liquid, powder, paste, or combinations thereof. The oral care composition can be dentifrice, nanogel, nanoparticles gel, nanoemulsion, tooth gel, subgingival gel, mouth rinse, mousse, foam, mouth spray, lozenge, chewable tablet, chewing gum, tooth whitening strips, floss and floss coatings, breath freshening dissolvable strips, or denture care or adhesive product. The components of the dentifrice composition can be incorporated into a film, a strip, foam, or a fiber-based dentifrice composition. The dentifrice composition can include a variety of active and inactive ingredients, such as, for example, but not limited to a calcium abrasive, water, a fluoride source, zinc ion source, one or more polyphosphates, humectants, surfactants, other ingredients, and the like, as well as any combination thereof, as described below. Detailed description of the Invention: The present invention relates to a synergistic dentifrice composition containing a water-soluble fluorine-containing compound for sustained release and retention of fluoride ions in the oral cavity for reducing the abrasivity of dentifrice at least one zinc salt, Arginine hydrochloride, Potassium Nitrate, Nano Hydroxyapatite, and Curcuma Longa extract to prevent and treatment of patients suffering from oral leukoplakia, oral lichen planus, oral submucous fibrosis, erythroplakia, periodontal disease and dental caries, dentinal hypersensitivity, ulcers, promoting remineralization and inhibiting demineralization, Xerostomia conditions of the mouth in a manner that is effective, efficient, and results in minimal undesirable side effects. The present invention is used for the management of pain and relief of pain, by adhering to the mucosal surface of the mouth, soothing oral lesions of various etiologies, including: Oral Mucositis / Stomatitis (may be caused by chemotherapy or radiotherapy), irritation due to oral surgery, traumatic ulcers caused by braces or ill fitting dentures, or disease. Also indicated for diffuse aphthous ulcers. In one embodiment of the invention, synergistic formulation consists of Arginine hydrochloride, NaF solution, Potassium Nitrate, Nano Hydroxyapatite, Curcuma Longa extract and zinc citrate. In another embodiment of the invention, synergistic formulation consists of 2.5% arginine, 500 ppm NaF, 1.5% Potassium Nitrate, 0.2% Nano Hydroxyapatite, 7% Curcuma Longa extract and 0.9% zinc citrate. In yet another embodiment of the invention, synergistic formulation consists of 2.5% arginine, 500 ppm NaF, 1.5% Potassium Nitrate, 0.2% Nano Hydroxyapatite, 7% Curcuma Longa extract and 0.9% zinc salts (zinc oxide and zinc citrate; 1:1, 1:10, 10:1). In one embodiment of the invention synergistic formulation consists of 0.5-7.5% arginine, 500-1500 ppm NaF, 0.5-5% Potassium Nitrate, 0.1-2% Nano Hydroxyapatite, 2-10% Curcuma Longa extract and 0.2-2% zinc salts (zinc oxide and zinc citrate; 1:1, 1:10, 10:1). In other embodiment of the invention synergistic formulation consists of at least two combination of two of ingredients of 0.5-7.5% arginine, 500-1500 ppm NaF, 0.5-5% Potassium Nitrate, 0.1-2% Nano Hydroxyapatite especially Zinc- Hydroxyapatite, 2-10% Curcuma Longa extract and 0.2-2% zinc salts (zinc oxide and zinc citrate; 1:1, 1:10, 10:1). In other embodiment of the invention synergistic formulation consists of at least two combination of two of ingredients of 0.5-7.5% arginine, 500-1500 ppm NaF, 0.5- 5% Potassium Nitrate, 0.1-2% Nano Hydroxyapatite especially Zinc-Hydroxyapatite, 2-10% Curcuma Longa extract, 0.2-2% zinc salts (zinc oxide and zinc citrate; 1:1, 1:10, 10:1) and 0.2-10%Myrtus communis. In other embodiment of the invention synergistic formulation consists of at least two combination of two of ingredients of 0.5-7.5% arginine, 500-1500 ppm NaF, 0.5-5% Potassium Nitrate, 0.1-2% Nano Hydroxyapatite especially Zinc- Hydroxyapatite, 2-10% Curcuma Longa extract, 0.2-2% zinc salts ((zinc oxide and zinc citrate; 1:1, 1:10, 10:1) and 0.2-10%Myrtus communis and peptides ( one or more than one peptides SEQ ID NO.1-96) In yet another embodiment of the invention synergistic formulation consists of 0.5- 7.5% arginine, 500-1500 ppm NaF, 0.5-5% Potassium Nitrate, 0.1-2% Nano Hydroxyapatite, 2-10% Curcuma Longa extract and 0.2-2% zinc salts ((zinc oxide and zinc citrate; 1:1, 1:10, 10:1) and methyl ester-benzo-lipoxin A4 ((5S, 6R, E)-methyl- 5,6-dihydroxy-8-(2-((R,E)-3-hydroxyoct-1-enyl) phenyl) oct-7-enoat) (0.5 -2 μM) to increase the efficiency to treat gingival inflammation. In yet another embodiment of the invention synergistic formulation consists of 0.5- 7.5% arginine, 500-1500 ppm NaF, 0.5-5% Potassium Nitrate, 0.1-2% Nano Hydroxyapatite, 2-10% Curcuma Longa extract and 0.2-2% zinc salts ((zinc oxide and zinc citrate; 1:1, 1:10, 10:1) and 3.4% tetrasodium pyrophosphate to increase the efficiency to prevention of plaque formation. In yet another embodiment of the invention synergistic formulation consists of 0.5- 7.5% arginine hydrochloride, 500-1500 ppm NaF, 0.5-5% Potassium Nitrate, 0.1-2% Nano Hydroxyapatite, 2-10% Curcuma Longa extract and 0.2-2% zinc salts ((zinc oxide and zinc citrate; 1:1, 1:10, 10:1), 3.4% tetrasodium pyrophosphate, Annona Muricata leaf extract (0.2-10%) and peptide(s). In other another embodiment of the invention synergistic gel formulation consists of Curcumin (1 and 2%) , 30% of pluronic F127, and 1% -2% of carbopol P934. In yet another embodiment of the invention synergistic formulation consists of optional ingredients of O-Cymen^5-ol (cymenol) 0.1% and tocopheryl acetate 0.2%. In yet another embodiment of the invention synergistic formulation consists of optional ingredients of O-Cymen-5-ol (cymenol) 0.1%; sodium monoflu- orophosphate 0.8%; dipotassium glycyrrhizate 0.15% and tocopheryl acetate 0.2%. In yet another embodiment of the invention synergistic formulation consists of Nano Hydroxyapatite is coating with alginate–Catechol / Fe2+ Coating to increase the antimicrobial activity. In yet another embodiment of the invention, production of hydroxyapatite sol-gels: a)Triethyl phosphite ([P(C2H50)3], Aldrich, USA) of 0.1 moles is hydrolyzed in ethanol with distilled water for 72 hours; b)The hydrolysed TEP is then slowly added to a 0.16 mole solution of calcium nitrate [Ca(NO3)2.4H20, Aldrich USA] and allowed to mix for 24 hours, c) A 5% solution of ammonium hydroxide (NH4OH, BDH, UK) and 100ml water is added to the solution in order to improve gelation and the polymerization of an apatite structure, d) Subsequent aging is allowed for 24 hours at room temperature. E) Oven drying is undertaken for a further 24 hours, e) With the use of an ammonium fluoride (NH4F) precursor fluoride substitution can be controlled into the apatite structure such that it is possible to make; Ca10(PO4)6F2, Ca10(PO4)6OH0.5F1.5, Ca10(PO4)6OH1F1 and Ca10(PO4)6OH1.5F0.5; the sol-gel technique used produced hydroxyapatite (HA), fluorapatite (FA) and fluorhydroxyapatite (FHA) that showed varying thermally stabilities, heating from 500oC to 1000oC caused a decrease in the unit cell size of the apatite structure for HA, FA and FHA obtained from the sol-gel technique used; Increasing fluoride ion substitution in the apatite structure caused a decrease in the unit cell size; this can be solely attributed to changes in the a – axis of the apatite structure, The higher the concentration of fluoride in the sol-gel the higher the viscosity i.e. the viscosity of the sol-gels was as follows; Ca10(PO4)6F2 > Ca10(PO4)6OH0.5F1.5 > Ca10(PO4)6)OH1F1 > Ca10(PO4)6OH1.5F0.5 > Ca10(PO4)6(OH)2; The higher the concentration of fluoride in the sol-gel the higher the contact angle i.e. the contact angle of the sol-gels on titanium was as follows; Ca10(PO4)6F2 > Ca10(PO4)6OH0.5F1.5 > Ca10(PO4)6OH1F1 > Ca10(PO4)6OH 1.5F0.5 > Ca10(PO4)6(OH)2; the dissolution rates of the fluoride-substituted powders from the sol^gels were considerably lower than that of HA; The observed dissolution rates (Ca10(PO4)6(OH)2 > Ca10(PO4)6F0.5OH1.5 > Ca10(PO4)6F1OH1 > Ca10(PO4)6F1.5OH0.5 > Ca10(PO4)6F2) suggest the possibility of tailoring the solubility of any coatings made from the sol-gels through fluoride ion substitution; the higher the temperature the sol-gel was heated to, the lower to ion release and thus dissolution rate; the dissolution rate followed the pattern of 600oC > 700oC > 800oC > 1000o C suggesting the possibility of tailoring the solubility of any coating made from this sol-gel route by increasing the firing temperature. In yet another embodiment of the invention, tooth paste is prepared by weighing all the ingredients and verify the weight, heat distilled water in the main vessel and heat up to 80°C with stirring, ingredients in the main vessel one by one with continuous stirring and mixed homogeneously, dd base material with continuous stirring and allow to cool at 40°C and add flavor at room temperature. In yet another embodiment of the invention synergistic oral gel formulation consists of Curcuma longa (5-20 mg) more preferably 10 mg, zinc citrate (0.1-10 mg), more preferably 0.2 mg, Glycyrrhiza glabra (5-10mg), more preferably 8 mg, Acacia catechu (3-6mg) more preferably 5 mg , Punica Granatum (5-20mg), more preferably 10 mg , and Mentha piperita (1-5 mg ) more preferably 2 mg . In yet another embodiment of the invention, oral gel is prepared by Carbopol 934 is accurately weighed in a beaker and dispersed in distilled water till the carbopol swelled, After swelling of carbopol, hydroxypropylmethylcellulose (HPMC) E 5 is added and stirred using mechanical / lab stirrer at 1000 rpm for 30- 40 m; ethanol was taken in required quantity of synergistic oral gel active materials and mixing with Propylene glycol followed by preservatives is added along with menthe oil with constant stirring at 1200 rpm; finally mixing all ingredients are transferred and with constant stirring at 1200 rpm. In yet other embodiment of the invention, formulation of Oral Mucoadhesive tablets with synergistic formulation ingredients with Avicel (10%), and Magnesium stearate (1%) and Cordia myxa Mucilage (20%). In yet other embodiment of the invention, Oral Mucoadhesive tablets preparation method is done by direct constant compression pressure using mixtures of the ingredients. In other embodiment of the invention synergistic formulation consists optional inactive ingredients of 0.01-0.05% Centella asiatica extract, 0.01-0.02% Polygonum cuspidatum root extract, 0.01-0.02% Scutellaria baicalensis root extract, 0.005- 0.01% Camellia sinensis leaf extract, 0.005-0.01% Glycyrrhiza glabra (licorice) root extract, 0.005-0.01% Chamomilla recutita (Matricaria) flower extract, 0.001-0.005% Rosemary rosmarinus officinalis leaf extract, 0.001-0.005% Salvia officinalis, Bamboo Salt, sodium methyl cocoyl taurate, Helianthus anuus seed oil, polyglyceryl-3 palmitate, polyglyceryl-6 caprylate, Usnea barbata extract, propolis extract, natural essential oils, melia azadirachta extract, krameria triandra extract, ricinus communis oil, salvia officinalis extract, stevia rebaudiana, aloe barbadensis gel, commiphora myrrha extract, Ocimum gratissimum extract, Chrysanthemum extract and other suitable extracts. In yet other embodiment of the invention may bisbiguanide (0.005% - 3% by wt. of the total composition such as chlorhexidine digluconate; cationic active agent such as quaternary ammonium surfactants, other polymers, and combinations thereof. In yet other embodiment of the invention may zinc ions is selected from the group consisting of zinc citrate, zinc lactate, zinc phosphate, and zinc oxide (e.g., wherein the source of zinc ions is in an amount from 0.1% - 3% by wt. of the composition) In yet other embodiment of the invention may surfactant comprises sodium laurel ether sulfate (SLES), sodium lauryl sulfate, and ammonium lauryl sulfate with an amount of 0.01 to 5.0%, 0.1 to 2.0%, 0.1 to 1.0%, 0.2 to 0.4%, or about 0.33%. In yet other embodiment of the invention may consists of a fluoride ion source such as stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride (e.g., N'-octadecyltrimethylendiamine- N,N,N'-tris(2-ethanol)- dihydrofluoride), ammonium fluoride, titanium fluoride, hexafluorosulfate, or a mixture thereof. In yet other embodiment of the invention synergistic formulation consists of optional ingredients of one or more than one peptides (0.001-10%) to increase the efficiency to treat the different oral diseases such as oral leukoplakia, oral lichen planus, oral submucous fibrosis, erythroplakia, periodontal disease and dental caries, dentinal hypersensitivity, ulcers, promoting remineralization and inhibiting demineralization, Xerostomia conditions, promote dental pulp wounds, Mucositis / Stomatitis, irritation due to oral surgery, traumatic ulcers caused by braces or ill fitting dentures,ulcer or disease as follows: GKGNNRPVYIPQPRPPHPRL (SEQ ID NO: 1) GKVDKGSYLPRPTPPRPIYNRN (SEQ ID NO: 2) GKZCRRLCYKQRCVTYCRGR (SEQ ID NO: 3) GKILPWKWPWWPWRR-NH2(SEQ ID NO: 4) GKGIGAVLKVLTTGLPALISWIKRKRQQ-NH2(SEQ ID NO: 5) GKGLFDIIKKIAESF(SEQ ID NO: 6) GKWKSFLKTFKSAKKTVLHTALKAISS–amide (SEQ ID NO: 7) GKALWKKLLKKLLKSAKKLG (SEQ ID NO: 8) GKILPWKWPWWPWRR-NH2(SEQ ID NO: 9) GKVRRFPWWWPFLRR (SEQ ID NO: 10) GKFIKRIARLLRKIF (SEQ ID NO: 11) GKINKAIAALAKKLL-NH2 (SEQ ID NO: 12) GKALLAHALAHLALLALHLALHLKKA-Amide (SEQ ID NO: 13) GKLLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (SEQ ID NO: 14) GKLKRIKTLL-NH2 (SEQ ID NO: 15) GKTFFYGGSRGKRNNFKTEEY (SEQ ID NO: 16) GKKVVFWVKFK-NH2(SEQ ID NO: 17) GKCKDEPQRRSARLSAKPAPPKPEPKPKKAPAKK (SEQ ID NO: 18) GKCRGDK (SEQ ID NO: 19) GKRGPD (SEQ ID NO: 20) GKEC (SEQ ID NO: 21) GKAGRGRLVR (SEQ ID NO: 22) GKAKRGARSTA (SEQ ID NO: 23) GKACYCRIPACIAGERRYG TCIYQGRLWAFCC (SEQ ID NO: 24) GKGGLRSLGRKILRAWK KYG(SEQ ID NO:25) GKFALGKVNAKLQSLN AKSLKQSGCC (SEQ ID NO:26) GKRAGLQFPVG (SEQ ID NO: 27) GKWKLFKKI-P-KFLHS AKKF(SEQ ID NO: 28) GKWKLFKKIEKVGQNIR DGIIKAGPAVAVVGQATQIAK(SEQ ID NO: 29) GKWKVFKKIEKMGRNI RNGIVKAGPAIAVLGE AKAL (SEQ ID NO:30) GKFFGWLIKGAIHAGKA IHGLI (SEQ ID NO:31) GKLKLLKKLLKKLLKLL (SEQ ID NO: 32) GKZCRRLCYKQRCVTY CRGR(SEQ ID NO: 33) GKRRQRRTSKLMKRGGK LAKL-AKKLAKLAK- (KLAKLAK)2 (SEQ ID NO:34) GKC1RRWQWRMKKLG APSITC1VRRAF (SEQ ID NO:35) GKLLGDFFRKSKEKIGKEFKR IVQRIKDFLRNLVPRTES (SEQ ID NO: 35) G-K-K-W-W-K-K-W-Dip-K(SEQ ID NO:36) GKGIGAVLKVLTTGLPALIS WIKRKRQQ (SEQ ID NO: 37) GKGIGKFLHSAKKFGKAF VGEIMNSGG-QRLGNQ WAVGHLM (SEQ ID NO:38) GKGFFALIPKIISSPLFKTLL SAVGSALSSSGGQE(SEQ ID NO:39) GKRKEKIKKRIGKIDRL-NH2 (SEQ ID NO: 40) GKIAKRIWKILRR-NH2 (SEQ ID NO: 41) GKGLFDIVKKVAG-NH2 (SEQ ID NO:42) GKRLFRRVKKVAG-NH2 (SEQ ID NO:43) GKIAKRIWKILRRRLFRRVKKVAG-NH2 (SEQ ID NO:44) GKIAKRIWKILRRRLFRRV-NH2 (SEQ ID NO:45) GKIAKRIWKILRRRLFRR-NH2 (SEQ ID NO:46) GKIAKRIWKILRRRLF-NH2(SEQ ID NO: 47) GKIAKRIWKILRRRL-NH2(SEQ ID NO:48) GKIAKRIWKILRRR-NH2(SEQ ID NO: 49) GKFKFLARTGKL-NH2(SEQ ID NO: 50) GKFSKLAGKKIKNLLISGLKNIGKEVGM (SEQ ID NO:51) GKLKDWVKKALGSLWKLANSQKAIISGKKS (SEQ ID NO:52) GKWKLFKKIWSSVKLKS (SEQ ID NO:53) GKWKSFIKKLAKFGFKVIKKFAKKHGSKIAKNQ (SEQ ID NO: 54) GKGILSSFKGVLKGAGKNLLGSLKDKLKN (SEQ ID NO: 55) GKRLARIVVIRVAR (SEQ ID NO: 56) GKRRAAHGLLPRLRAPPPFHKRCVCLCRTAPPP (SEQ ID NO: 57) GKRRAAHGLLPRLRAPPPFHKR (SEQ ID NO: 58) GKRLRAPPPFHKRCVC (SEQ ID NO: 59) GKHVLDTPLL (SEQ ID NO: 60) GKGLLGKILGAGKKVLLGVSGLL (SEQ ID NO: 61) GKTLVNSVNSK (SEQ ID NO: 62) GKELVRKDLQN (SEQ ID NO: 63) GKGLLGKILGAGKKVL (SEQ ID NO: 64) GKLLETECPQ (SEQ ID NO: 65) GKNTDGAVNFQ (SEQ ID NO: 66) GKNADKQLSFE (SEQ ID NO: 67) G-K-Lys-Leu-Leu-Glu-Thr-Glu-Cys-Pro-Gln (SEQ ID NO: 68) G-K-Asn-Thr-Asp-Gly-Ala-Val-Asn-Phe-Gln (SEQ ID NO: 69) G-K-Glu-Leu-Val-Arg-Lys-Asp-Leu-Gln-Asn (SEQ ID NO: 70) G-K-Asn-Ala-Asp-Lys-Gln-Leu-Ser-Phe-Glu (SEQ ID NO: 71) G-K-Lys-Leu-Leu-Glu-Thr-Glu-Cys-Pro-Gln (SEQ ID NO: 72) G-K-Lys-Leu-Leu-Glu-Thr-Glu-Cys-Pro-Gln-Tyr (SEQ ID NO: 73) G-K-Lys-Leu-Leu-Glu-Thr-Glu-Cys-Pro-Gln-Tyr-Ile (SEQ ID NO: 74) G-K-Asn-Thr-Asp-Gly-Ala-Val-Asn-Phe-Gln (SEQ ID NO: 75) G-K-Glu-Leu-Val-Arg-Lys-Asp-Leu-Gln-Asn (SEQ ID NO: 76) G-K-Asn-Ala-Asp-Lys-Gln-Leu-Ser-Phe (SEQ ID NO: 77) GKGGQQLK (SEQ ID NO: 78) GKGSVLGYIQIR (SEQ ID NO: 79) RADARADARADARADA-GGQQLK (SEQ ID NO: 80) GKRADARADARADARADA-GSVLGYIQIR (SEQ ID NO: 81) GKRLDLRLALRLDLR-CONH2 (SEQ ID NO: 82) GKLSGINAEWPC (SEQ ID NO: 83) GKVVEYGSNMT (SEQ ID NO: 84) GKEYGSNMTIE (SEQ ID NO: 85) GKVEKQLDLAA (SEQ ID NO: 86) GKVYWEMEDKN (SEQ ID NO: 87) GKEDLKVQHSS (SEQ ID NO: 88) GKCPPPPEKEKEKEK (SEQ ID NO: 89) GKRLFKKLLKYLRKF (SEQ ID NO: 90) GKLTDDYKKY(SEQ ID NO: 91) GKAASDISL(SEQ ID NO: 92) GKTHLW(SEQ ID NO: 93) GKRHHGYKRKFH (SEQ ID NO: 94) GKGlu Thr Ala Val Ser Ser His Glu Gln Asp (SEQ ID NO: 95) GKLLFLVTLPFWIHYVRGHNWVFGH(SEQ ID NO: 96) In yet embodiment of the invention, peptides may have modifications in the backbone or side chains. Modifications here are not limited as long as they do not interfere with the dentinogenic function of the peptide. The modification may be present atleast one site selected from the N-terminus, C-terminus of the main chain, and at least one side chain of the amino acid residues constituting the main chain. Peptides may also adopt a cyclic structure. In other embodiment of the invention, peptides may have modifications of the N- terminus include modifications commonly used as N-terminal modifications of peptides. For example, N-terminal modifications include azide modification, C1-6 acylation modification such as C1-6 alkanoyl (acetylation modification, formylation modification, etc.), succinylation modification, Boc modification, Fmoc modification, biotinylation modification, myristin. modification, palmitoylation modification, stearoylation modification, fluorescent dye modification (rhodamine labeling, FAM labeling, TAMRA labeling, etc.),methylation modification, pyroglutamylation modification, dansylation modification, and the like. In other embodiment of the invention, C-terminal modifications include modifications that are generally used as C-terminal modifications of peptides. For example, C-terminal modification includes amidation modification, biotinylation modification, methyl esterification modification, aldehyde modification, N- hydroxyesterification modification, pNA labeling, MCA labeling, β- naphthylamidation modification and the like. In other embodiment of the invention, modification of side chains of amino acid residues constituting the main chain includes polyethylene glycol modification, phosphorylation modification, acetylation modification, methylation modification, fluorescence modification, biotinylation modification, sugar or sugar chain modification, lipid modification, and the like can be mentioned. In some embodiments, the humectant includes glycerine or sorbitol or an alkylene glycol or Erythritol, saccharin, aspartame, stevia, acesulfame, sucralose, brazzein, pentadin, thaumatin, monellin, dihydrochalcones, polyethylene glycol or propylene glycol. In some embodiments, the humectant may be present in an amount of about 20% to about 80% by weight of the dentifrice composition. In other embodiments, the humectant may be present in an amount of about 50% to about 70% by weight. In other embodiments, an inorganic or a natural or synthetic thickener or gelling agent may be present in an amount of about 0.10% to about 10% by weight. The thickener or gelling agent may be present in an amount of about 0.1% to about 1% by weight. In some embodiments, suitable an inorganic or a natural or synthetic surfactants may include, but are not limited to, water-soluble salts of higher fatty acid monoglyceride monosulfates, likes cocamidopropyl betaine, the sodium salt of the monsulfated monoglyceride of hydrogenated coconut oil fatty acids, higher alkyl sulfates such as sodium lauryl sulfate, alkyl aryl sulfonates such as sodium dodecyl benzene sulfonate, alkyl sulfoacetates, sodium lauryl sulfoacetate, fatty acid esters of 1,2-dihydroxy propane sulfonate, and the considerably saturated higher aliphatic acyl amides of lower aliphatic amino carboxylic acid compounds, such as those having 12 to 16 carbons in the fatty acid, alkyl or acyl radicals, amides are N-lauroyl sarcosine, and the sodium, potassium, and ethanolamine salts of N-lauroyl, N- myristoyl, or N-palmitoyl sarcosine and the like. In some embodiments, the anionic surfactants are present in the dentifrice composition in an amount of about 0.1% to about 10% by weight. In other embodiments, the anionic surfactants are present in the dentifrice composition in an amount of about 0.2% to about 5% by weight. In some embodiments, the dentifrice composition may also contain suitable inorganic or a natural or synthetic binder agent and is not limited to, marine colloids,carboxyvinyl polymers, carrageenans, starches, cellulosic polymers such as hydroxyethylcellulose, carboxymethylcellulose (carmellose), hydroxypropyl methyl cellulose and salts thereof (e.g., carmellose sodium), natural gums such as karaya, xanthan, gum arabic and tragacanth, chitosan, colloidal magnesium aluminum silicate, hydrated and colloidal silica. In some embodiments, an inorganic or a natural or synthetic abrasives are added to the dentifrice formulation are not limited to silica abrasives such as precipitated EDTA, silicas, sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dihydrated dicalcium phosphate, aluminum silicate, calcined alumina, bentonite or other siliceous materials, particulate thermosetting resins, such as melamine, phenolic, and urea-formaldehydes, and cross-linked polyepoxides and polyesters. In some embodiments, additives may be included in the dentifrice composition for reasons of manufacturing, stability, aesthetics, therapeutic effect, consumer appeal, etc. are not limited to dentifrice additives, viscosity modifiers, diluents, foam modulators, saliva stimulating agents, desensitizing agents, whitening agents, enzymes, pH modifying agents, mouth-feel agents, sweeteners, colorants, opacifiers, and breath freshening agents. In some embodiments, other active agents not limited to Bloodroot, Caraway, Chamomile, Echinacea, Myrrh, Peppermint, Rosemary, Sage, Thyme, Aloe Vera, Propolis, Zingiber officinale, Rosmarinus officinalis, Calendula officinalis, Salvia officinalis, Mentha piperita, menthol, Matricaria chamomilla, Commiphora myrrha, Carvum carvi, Eugenia caryophyllus, Echinacea purpura, Matricaria chamomilla L., Punica granatum L., Centella asiatica,, Sambucus nigra, T. bellirica, T. chebula, P. emblica, P. kurroa, C. rotundus , C. deodara, T. cordifolia, H. antidysenterica, S. chirata, Cissampelos pareira, Rosmarinus officinalis. L, Vitis, vinifera, Cichorium intybus, Trigonella foenum-graecum L, Lavandula multifida L., Pistacia lentiscus , commiphora myrrha , Viola odorata, Curcuma zedoaria, Terminalia chebula, Rosa indica, Terminalia belerica, Piper nigrum, Cassia angustifolia, Cassia acutifolia, Terminalia chebula, Punica Granatum, Hypericum perforatum L., Chasmanthera dependens, Chenopodium ambrosioides, Kaempferia galangal and other suitable extracts In some embodiments, other active agents not limited to circimaritin, cirsilineol, isothymusin, rosmarinic acid, apigenin, ellagic acid, ellagitannins (including punicalagins), punicic acid, propolis , flavonoids, anthocyanidins, anthocyanins, estrogenic flavonols, 1,8-cineole (eucalyptol), β-pinene, α-caryophellene, 9-epi-(E)- caryophellene, β-sitosterol, Lippia sidoides, Magnolol , honokiol, apigenin, α- bisabolol and cyclic ethers, umbelliferone, chamazulene and other suitable agents. In some embodiments, active agents are not limited to herbal extracts, combination of herbal extract (s) with other active agents, NSAIDs, enzyme (s) such as papain, oxidoreductase enzyme, alpha-amylase, proteolytic enzyme, dextranase, a Paecilomyces lilacinum dextranase, mutanase, Glucoseoxidase, Amyloglucosidase, lactoperoxidase, lactoferrin, colostrum, amyloglucosidase, glucose oxidase, lactoperoxidase a fluoride ion source, stannous fluoride, stannous chloride dihydrate, stannous acetate, stannous gluconate, stannous oxalate, stannous sulphate, stannous lactate, stannous tartrate, polycarboxylate polymers, steroids, hexetidine, sanguinarine, as fluoride ion providing compound, sodium fluoride, monosodium fluoride, calcium fluoride, and arginine salts, arginine bicarbonate, arginine phosphate, arginine bicarbonate benzalkonium chloride, N-tetradecyl-4- ethylpyridiniumchloride, polyvinyl methyl ether, maleic anhydride, copolymers, an arginine ester, a zinc ion source, a stannous ion source, delmopinol, tartar control agents, an antibacterial agent, tetradecylpyridinium chloride, triclosan and salts thereof, chlorhexidine, alexidine, salicylanilide, domiphen bromide, cetylpyridinium chloride, octenidine, octapinol, nisin, a zinc ion source, strontium edatate, Benzalkonium Chloride, bicarbonate salt, a copper ion source, an essential oil, potassium nitrate, aluminum lactate, strontium chloride, a furanone, hydroxyapatite, anti-inflammatory agents, antiplaque agents, antioxidants, and a bacteriocins, and salts thereof, honokiol, isopropylmethylphenol, α-olefin sulfonate, vitamins, anti- attachment agents, proteinaceous agents, zinc ions are zinc chloride, zinc acetate, zinc gluconate, zinc sulphate, zinc fluoride, zinc citrate, zinc lactate, zinc oxide, zinc monoglycerolate, zinc tartrate, zinc pyrophosphate zinc maleate, Pyrophosphate, silver particles, gold particles, nanoparticles and peptides. In some embodiments, pH adjuster is not limited to citric acid and salts thereof, phosphoric acid and salts thereof, malic acid and salts thereof, gluconic acid and salts thereof, maleic acid and salts thereof, aspartic acid and salts thereof, gluconic acid and salts thereof, succinic acid And salts thereof, glucuronic acid and salts thereof, fumaric acid and salts thereof, glutamic acid and salts thereof, adipic acid and salts thereof, inorganic acids such as hydrochloric acid, etc., hydroxylation such as hydrofluoric acid, sodium hydroxide, potassium hydroxide etc. And amines such as alkali metal, triethanol amine, diethanol amine, diisopropanol amine and the like. In yet other embodiment of the invention, flavoring agents such as coconut, grape fruit, orange, lime, lemon, mandarin, pineapple, strawberry, raspberry, mango, passion fruit, kiwi, apple, pear, peach, apricot, cherry, grapes, banana, cranberry, blueberry, black currant, red currant, gooseberry, lingon berries, thyme, basil, camille, valerian, fennel, parsley, spearmint, peppermint , chocolate , limonene, menthone, carvone, menthol, anethole, eucalyptus oil, eucalyptol, anethole, eugenol, cassia, oxanone, .alpha.-irisone, propenyl guaiethol, thymol, linalool, benzaldehyde, άnnamaldehyde, N-ethyl-p- menthan-3-carboxamine, N / 2,3- trimethyl-2-isopropylbutanamide, 3-1- menthoxypropane-l,2-diol, cinnamaldehyde glycerol acetal, methone glycerol acetal, cineole. and other suitable agents. In yet other embodiment of the invention, Dual-Chamber Packaging System for Optimal Ingredient Stability optionally i.e. A toothpaste formulation with two separate chambers; one for fluoride and one for calcium-containing ingredients. The chambers mix the ingredients at the point of use to prevent premature interaction and ensure maximum efficacy. In yet other embodiment of the invention, semisolid and solid form of dentifrice stored in toothbrush handle with retractable try or pushing system to avoid logistic issue during travelling and other places wherein toothbrush head and handle is replaceable. A kit comprising a dentifrice formulation, where the formulation includes two or more active ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts, and optionally a peptide with 7-30 amino acid residues. The kit is designed to address dentine hypersensitivity, dental pain, and promote oral health by reducing plaque, gingival inflammation, inhibiting demineralization, and promoting remineralization. The kit includes a container holding the formulation, and printed instructions or a leaflet providing directions for use and detailing the oral conditions that can be treated, including leukoplakia, lichen planus, periodontal disease, dental caries, and xerostomia. Dual-Chamber Packaging Kit: A kit comprising a dual-chamber packaging system for separating any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid within the dentifrice formulation until the point of use, to prevent premature interaction and ensure optimal efficacy of each component. The kit further includes human-readable indications for the use of the composition in managing oral conditions such as enamel remineralization and reducing plaque formation. A kit containing a customizable oral care formulation, wherein users can select the concentration of specific active ingredients based on their individual needs, such as enhanced zinc salt concentrations for antibacterial effects or increased potassium nitrate for hypersensitivity relief. The kit includes mixing instructions for combining components at home or in a clinical setting to create a formulation tailored to specific oral health conditions. A compact kit designed for portability, comprising: Single-use sachets or tubes of the dentifrice formulation, pre-portioned for daily use. A travel-sized soft-bristled toothbrush with a built-in dispenser for the formulation. A collapsible cup for mouth rinsing, and optional dental floss or interdental brushes infused with antibacterial agents for enhanced oral hygiene. User instructions for maintaining oral health on- the-go, targeting frequent travelers who need easy access to a complete oral care solution. A kit designed for use by dental professionals in clinical settings, comprising: A dentifrice formulation with higher concentrations of active ingredients such as any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues for immediate relief of dentine hypersensitivity and enamel remineralization during treatment. Subgingival application tools, including syringes or brush applicators, for precise delivery of the formulation to affected areas.A protective storage system for maintaining the stability and efficacy of the formulation during long-term storage.Optional diagnostic strips or tests to assess the severity of oral conditions like plaque accumulation or enamel demineralization before and after treatment. A subscription model kit providing a monthly supply of the dentifrice formulation and related oral care products.The kit includes a base formulation and periodic additions of specialized components (e.g., higher fluoride concentration or Curcuma longa extract) based on the user's evolving oral health needs. The subscription includes access to a digital platform where users can track their oral health progress, receive personalized care recommendations, and adjust their monthly product shipment based on specific concerns like hypersensitivity, gingivitis, or plaque buildup. A system comprising: The dentifrice formulation, in a form suitable for treating dentine hypersensitivity, enamel demineralization, and oral diseases like lichen planus and leukoplakia. Optional delivery mechanisms such as a toothpaste tube, spray bottle, or lozenge that are designed to provide controlled release of the active ingredients. A user guide detailing how to apply the product for optimal results, along with a digital platform for tracking oral health improvements over time. A subscription model kit providing a monthly supply of the dentifrice formulation and related oral care products. The kit includes a base formulation and periodic additions of specialized components (e.g., higher fluoride concentration or Curcuma longa extract) based on the user's evolving oral health needs. The subscription includes access to a digital platform where users can track their oral health progress, receive personalized care recommendations, and adjust their monthly product shipment based on specific concerns like hypersensitivity, gingivitis, or plaque buildup. A system for managing oral health that includes:A dentifrice formulation comprising the active ingredients, designed to be delivered in multiple forms such as toothpaste, mouth rinse, gel, or dental spray.The system includes user instructions for application and usage frequency, based on the specific oral condition being treated (e.g., dentine hypersensitivity or gingival inflammation). Optional accessories such as a soft-bristled toothbrush or applicator designed to enhance the delivery and efficacy of the formulation. Digital access to additional educational resources on oral health management through a smartphone app or website. A system comprising: The dentifrice formulation, in conjunction with an oral health monitoring device such as a smart toothbrush or an oral pH sensor. The system allows for real-time monitoring of oral health metrics such as plaque levels, enamel demineralization, and oral acidity, and provides feedback through a connected mobile app. The dentifrice formulation is adjusted over time based on the user's oral health data, promoting personalized oral care. A system comprising: A multi-step oral care regimen, starting with a plaque-control mouth rinse containing any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues , followed by brushing with the dentifrice formulation to treat dentine hypersensitivity and gingival inflammation. An optional post-brushing application of a gel containing hydroxyapatite and fluoride for enhanced enamel remineralization. The system includes printed or digital instructions for the correct sequence and timing of product use to maximize therapeutic benefits. A system comprising: A dual-phase dispensing mechanism for the dentifrice formulation, separating components that need to remain stable until the point of use (e.g., fluoride and calcium-based ingredients). The dispensing system mixes the components as they are extruded, ensuring maximum efficacy of the formulation in treating conditions like enamel demineralization and dental caries. The system includes a tracking mechanism (e.g., digital or mechanical) to monitor product usage and alert the user when it’s time for a refill. A system designed for sustained oral care, comprising: A dentifrice formulation with encapsulated active ingredients that release over time, providing long-lasting protection against plaque, gingivitis, and enamel demineralization. The system includes a time-released gel or toothpaste, which is applied once a day and continues to deliver therapeutic effects over 24 hours. Instructions are provided for proper application, including guidance on how to maximize the sustained effects of the formulation for chronic conditions like dentine hypersensitivity or periodontal disease. A system comprising: A higher-strength dentifrice formulation for clinical use, containing potent concentrations of zinc salts, arginine hydrochloride, and fluoride.Tools for professional application, including interdental brushes and applicator syringes for subgingival administration of the formulation. The system includes clinical documentation for dentists or healthcare professionals detailing the treatment protocol, recommended frequency of application, and expected outcomes for conditions like gingival inflammation, enamel erosion, and periodontal disease. A method for treating dentine hypersensitivity comprising the following steps: Providing a dentifrice formulation containing any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues. Dispensing an amount of the formulation onto a soft-bristled toothbrush. Applying the dentifrice formulation to the teeth, focusing on areas with exposed dentine, where sensitivity is experienced. Brushing the teeth for 2 minutes, ensuring gentle circular motions on sensitive areas. Rinsing the mouth with water after brushing. Repeating the process twice daily, preferably after meals, for a minimum of 4 weeks to achieve noticeable reduction in hypersensitivity. A method for enhancing enamel remineralization comprising the following steps: Providing a dentifrice formulation containing at least sodium fluoride (1.1% by weight) and hydroxyapatite (3% by weight). Dispensing the formulation onto a medium-bristle toothbrush. Brushing the teeth with the formulation for 2 minutes, focusing on areas prone to demineralization or previous cavities. Ensuring the formulation remains on the teeth for an additional 1 minute after brushing to allow absorption of fluoride and hydroxyapatite. Rinsing the mouth lightly, leaving a thin protective layer of the formulation on the teeth. Repeating the process twice daily, particularly after exposure to acidic foods or beverages, to help remineralize weakened enamel and prevent further decay. A method for reducing plaque formation and treating gingival inflammation comprising the following steps:Providing a dentifrice formulation containing any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues. Dispensing the formulation onto a toothbrush. Brushing the teeth thoroughly, ensuring that the brush reaches the gum line and interdental spaces. Massaging the gums gently with the brush, allowing the Curcuma longa extract and peptides to penetrate gingival tissues for at least 1 minute. Spitting out excess dentifrice but avoiding rinsing with water immediately to allow the actives to remain in contact with the teeth and gums. Repeating the method twice daily, particularly after meals, to reduce plaque buildup and inflammation. A method for treating both dentine hypersensitivity and enamel demineralization comprising the following steps: Providing a dentifrice formulation containing any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues. Applying the formulation to a soft- bristled toothbrush. Brushing the teeth for 2-3 minutes, ensuring that areas of exposed dentine and demineralized enamel are thoroughly covered. Allowing the formulation to remain on the teeth for an additional 2 minutes after brushing. Rinsing the mouth lightly, leaving some residual fluoride and hydroxyapatite on the enamel surface. Repeating the method twice daily to reduce sensitivity and promote enamel remineralization over time. A method for preventing dental caries comprising the following steps: Providing a dentifrice formulation containing sodium fluoride (1.1% by weight). Dispensing the formulation onto a toothbrush. Brushing the teeth for 2 minutes, ensuring all tooth surfaces, particularly in high-risk areas such as molars and interdental spaces, are adequately coated with the fluoride formulation. Rinsing the mouth with water after brushing. Using the dentifrice formulation twice daily, in the morning and before bed, to strengthen enamel and protect against bacterial acid attacks. A method for reducing gingival inflammation and promoting gum health, comprising the following steps: Providing a dentifrice formulation containing any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues. Dispensing the formulation onto a soft toothbrush or finger brush. Gently massaging the gums with the formulation for 1-2 minutes, ensuring that the active ingredients penetrate the gingival tissues. Rinsing the mouth with water after the massage. Repeating the process twice daily, with particular attention to inflamed areas, to reduce inflammation and support gum regeneration. A method for enhancing oral health using an ultrasonic toothbrush, comprising the following steps: Providing a dentifrice formulation containing any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues. Dispensing the formulation onto an ultrasonic toothbrush. Brushing the teeth using the ultrasonic toothbrush for 2 minutes, allowing the ultrasonic vibrations to enhance the penetration of active ingredients into the enamel and gums. Ensuring that the brush reaches all surfaces of the teeth and the gum line. Rinsing the mouth after brushing. Repeating the method twice daily to achieve superior plaque removal, gum health, and sensitivity reduction. A method for improving oral health by combining a pre-rinse with the dentifrice formulation, comprising the following steps: Providing a pre-rinse containing any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues. Rinsing the mouth with the pre-rinse for 30 seconds before brushing to remove loose debris and prepare the oral cavity for the dentifrice. Dispensing a dentifrice formulation containing sodium fluoride and Curcuma longa extract onto a toothbrush. Brushing the teeth for 2 minutes, focusing on the gum line and interdental spaces. Rinsing the mouth with water after brushing. Repeating the method twice daily to enhance plaque control and provide prolonged antibacterial action. School Programs: Travel-sized kits and subscription kits could be ideal for distribution in schools for maintaining children’s oral health, especially if the formulations are tailored to prevent dental caries and promote gingival health. Sports Programs: Time-released dentifrice systems could be applied for athletes in sports teams, particularly for the treatment of mouth injuries or trauma-related dental sensitivity. The technical solution also provides a preparation method of an oral care product, which comprises the following steps in sequence: EXAMPLES The invention is further illustrated by the following examples, which are not to be construed in any way as imposing limitations to the scope of this invention. Various other aspects, modifications, and equivalents thereof which, after reading the description herein, may suggest themselves to one of ordinary skill in the art without departing from the spirit of the present invention or the scope of the appended claims. Example 1: Dentifrice compositions according to the present invention are shown below with amounts of ingredients in weight %. Table 1: Dentifrice composition (Tooth Paste) Sr. no. Ingredients Quantity in % 1 Calcium Carbonate (toothpaste 20-50 grade) 2 Sodium Cocoyl Glutamate 10-20 3 Sorbitol 70% 5-20 4 DM Water 1-90 5 Curcuma Longa (Rhizome extract) 0.5-20 6 Arginine Hydrochloride 0.5-8 7 Glycerine 1-30 8 Erythritol 0.5-5 9 Abrasive Silica 0.5-10 10 Potassium Nitrate 0.2-10 11 Sodium CMC 0.2-2 12 Elettaria cardamomum (Seed 0.1-5 extract) 13 Foeniculum vulgare (Fruit extract) 0.1-5 14 Flavour 0.1-0.5 15 Melaleuca leucadendra (Leaf 0.1-5 extract) 16 Eucalyptus globules (leaf extract) 0.1-5 17 Aloe barbadensis (Leaves Pulp 0.1-5 extract) 18 Sodium Saccharin 0.1-5 19 Carnosic Acid 0.1-5 20 Zinc citrate 0.1-5 21 Nano Hydroxyapatite 0.1-5 22 Propolis 0.1-5 23 Myrtus communis (Whole plant) 0.1-5 extract 24 Hippophae rhamnoides (Fruit) 0.1-5 extract 25 Syzygium aromaticum (Bulb) extract 0.1-5 26 Sodium Fluoride 0.02-0.006 27 Sodium Benzoate 0.005-0.01 Table 2: Dentifrice composition (Toothpaste) Sr. no. Ingredients Quantity in % 1 Calcium Carbonate (toothpaste 20-50 grade) 2 Sodium Cocoyl Glutamate 10-20 3 Sorbitol 70% 5-20 4 DM Water 1-90 5 Curcuma Longa (Rhizome extract) 0.5-20 6 Arginine Hydrochloride 0.5-8 7 Glycerine 1-30 8 Erythritol 0.5-5 9 Abrasive Silica 0.5-10 10 Potassium Nitrate 0.2-10 11 Sodium CMC 0.2-2 12 Elettaria cardamomum (Seed 0.1-5 extract) 13 Foeniculum vulgare (Fruit extract) 0.1-5 14 Flavour 0.1-0.5 15 Melaleuca leucadendra (Leaf 0.1-5 extract) 16 Eucalyptus globules (leaf extract) 0.1-5 17 Aloe barbadensis (Leaves Pulp 0.1-5 extract) 18 Sodium Saccharin 0.1-5 19 Carnosic Acid 0.1-5 20 Zinc citrate 0.1-5 21 Nano Hydroxyapatite 0.1-5 22 Propolis 0.1-5 23 Myrtus communis (Whole plant) 0.1-5 extract 24 Hippophae rhamnoides (Fruit) 0.1-5 extract 25 Syzygium aromaticum (Bulb) extract 0.1-5 26 Sodium Fluoride 0.02-0.006 27 Sodium Benzoate 0.005-0.01 28 O-Cymen-5-ol (cymenol) 0.001-0.5 29 Dipotassium glycyrrhizate 0.001-0.2 30 Tocopheryl acetate 0.001-0.3 Table 3: Dentifrice composition (Tooth Paste) Sr. no. Ingredients Quantity in % 1 Calcium Carbonate (toothpaste 30-40 grade) 2 Sodium Cocoyl Glutamate 15-25 3 Sorbitol 70% 10-20 4 DM Water 5-10 5 Curcuma Longa (Rhizome extract) 5-10 6 Arginine Hydrochloride 1-2 7 Glycerine 2-3 8 Erythritol 1-3 9 Abrasive Silica 1-3 10 Potassium Nitrate 1-2 11 Sodium CMC 0.5-1.5 12 Elettaria cardamomum (Seed 0.2-1 extract) 13 Foeniculum vulgare (Fruit extract) 0.2-1 14 Flavour 0.2-0.6 15 Melaleuca leucadendra (Leaf 0.1-0.3 extract) 16 Eucalyptus globules (leaf extract) 0.1-0.3 17 Aloe barbadensis (Leaves Pulp 0.1-0.3 extract) 18 Sodium Saccharin 0.1-0.3 19 Carnosic Acid 0.1-0.3 20 Zinc citrate 0.1-0.3 21 Nano Hydroxyapatite 0.1-0.3 22 Propolis 0.1-0.3 23 Myrtus communis (Whole plant) 0.05-0.15 extract 24 Hippophae rhamnoides (Fruit) 0.05-0.15 extract 25 Syzygium aromaticum (Bulb) extract 0.05-0.15 26 Sodium Fluoride 0.01-0.06 27 Sodium Benzoate 0.005-0.15 Table 4: Dentifrice composition (Tooth paste) Sr. no. Ingredients Quantity in % 1 Calcium Carbonate (toothpaste 30-40 grade) 2 Sodium Cocoyl Glutamate 15-25 3 Sorbitol 70% 10-20 4 DM Water 5-10 5 Curcuma Longa (Rhizome extract) 5-10 6 Arginine Hydrochloride 1-2 7 Glycerine 2-3 8 Erythritol 1-3 9 Abrasive Silica 1-3 10 Potassium Nitrate 1-2 11 Sodium CMC 0.5-1.5 12 Elettaria cardamomum (Seed 0.2-1 extract) 13 Foeniculum vulgare (Fruit extract) 0.2-1 14 Flavour 0.2-0.6 15 Melaleuca leucadendra (Leaf 0.1-0.3 extract) 16 Eucalyptus globules (leaf extract) 0.1-0.3 17 Aloe barbadensis (Leaves Pulp 0.1-0.3 extract) 18 Sodium Saccharin 0.1-0.3 19 Carnosic Acid 0.1-0.3 20 Zinc citrate 0.1-0.3 21 Nano Hydroxyapatite 0.1-0.3 22 Propolis 0.1-0.3 23 Myrtus communis (Whole plant) 0.05-0.15 extract 24 Hippophae rhamnoides (Fruit) 0.05-0.15 extract 25 Syzygium aromaticum (Bulb) extract 0.05-0.15 26 Sodium Fluoride 0.01-0.06 27 Sodium Benzoate 0.005-0.15 28 Lys-Leu-Leu-Glu-Thr-Glu-Cys-Pro- 0.005-0.1) Gln ( BR29) Table 5: Dentifrice composition (Tooth paste) Sr. no. Ingredients Quantity in % 1 Elettaria Cardamomum 0.2-1 (Seed extract) 2 Foeniculum vulgare ( Fruit 0.2-1 extract) 3 Syzygium 0.2-1 Aromaticum ( Bulb extract) 4 Melaleuca 0.2-1 Alterifolia (Dried leaf extract) 5 Eucalyptus 0.2-1 Globules (Dried leaf extract) 6 Curcuma longa ( Rhizome 0.2-1 extract) 7 Tomato, curry leaf (Bulb 0.2-1 extract) 8 Sodium Carboxy 0.2-1 Methyl cellulose 9 Calcium 20-40 Carbonate 10 Silica 1-1.5 11 Sorbitol 20-35 12 Sodium 0.1-0.5 Saccharin 13 Sodium Benzoate 0.01 14 Glycerine 3 15 Arginine Hydrochloride 1-2 16 Nano Hydroxyapatite 0.1-5 17 Sodium Fluoride 0.02-0.006 18 Potassium Nitrate 1-2 19 Peptide 0.001-2 20 Aqua Q.S. Table 6: Dentifrice composition (Tooth paste) # Ingredient Qty % 1 Hippophae rhamnoides 0.08 2 Curcuma Longa 0.05 3 Glycerine IP 17 4 Sorbitol 40.1 5 Sodium Saccharin 0.15 6 Abrasive Silica 15 7 Hydrated Silica 8 8 Xanthan Gum 1.2 9 Sodium Carboxymethyl 1.2 Cellulose 10 Sodium Lauroyl Sarcosinate 3 11 Cocamidopropyl Betaine 2 12 Sodium fluoride 0.2 13 Mint Cool flavour 0.3 14 Menthol 0.3 # Ingredient Qty % 15 Colour Blue 0.01 16 DM Water 11.41 100 Table 7: Dentifrice composition (Mouth wash) Sr. no. Ingredients % 1 Sodium fluoride 0.01-1.4 2 Chlorhexidine acetate 0.5-4.3 3 Aspartame 2-14.3 4 Microcrystalline cellulose 20-74.3 5 Polyoxyethylene glycol 4000 1-5.7 6 Peppermint oil 0-0.3% 7 Arginine Hydrochloride 1-2 8 Nano Hydroxyapatite 0.1-5 9 Potassium Nitrate 1-2 10 Peptide 0.001-2 11 Colour 0.001-0.005 12 Flavor 0.001-0.01 13 distilled water Q.s Table 8: Dentifrice composition (Mouth wash) Sr.no. Ingredients % 1 Aspartame 6 2 Chlorhexidine 0.69 3 Sodium cyclamate 0.69 4 Glycerine 9.75 5 Sodium fluoride 0.05 6 Water Q.s 7 Tween 20 0.3 8 Xylitol 2 9 Sacarina 0.02 10 potassium nitrate 3 11 Mint flavor 0.05 12 Zinc Acetate 0.3 13 Arginine 0.8 14 Nano Hydroxyapatite 0.5 15 Tromethamine 2.4 16 Cethylpyridium chloride 0.7 17 Bio colour FD and C 1 0.2 puricolour ABL 9 (INCI code CI 42090) 18 Curcumin 0.05 19 Hippophae rhamnoides 0.05 Table 9: Dentifrice composition (Mouth wash) Sr. no. Ingredients % 1 Water Q.s 100 2 Chlorhexine diacetate 0.01-0.05 3 Potassium Acesulfame 0.01-0.05 4 Zinc Acetate 0.1-0.5 5 Hydrogenated starch 5-10 hydrolysate 6 Ethanol 0.5-1.5 7 Flavoring 0.5 8 PEG-40 hydrogenated 0.5-1.5 castor oil 9 Glycerin 9-15 10 Citric acid (50% aq) to pH 7 11 Tromethamine 2-5 12 Arginine Hydrochloride 1-2 13 Nano Hydroxyapatite 0.1-5 14 Potassium Nitrate 1-2 15 Peptide 0.001-2 16 Colour 0.001-0.005 17 Flavor 0.001-0.01 Table 10: Dentifrice composition (Mouth wash) # Ingredient Qty % 1 Hippophae rhamnoides extract 0.08 2 Curcuma Longa 0.05 3 Tea Tree Oil 0.06 4 Sodium Fluoride 0.05 5 Sodium Benzoate 0.1 6 Sodium Saccharin 0.15 7 Menthol 0.2 8 Mint Cool flavour 0.2 9 Polysorbate 20 6 10 Zinc acetate 0.2 11 Sorbitol 13 12 Hydroxyapatite 0.2 13 Potassium nitrate 1 14 Tromethamine 1.2 15 Arginine 0.3 16 Cetylpyridinium chloride 0.7 17 Colour Blue 0.01 18 DM Water QS Table 11: Dentifrice composition (Oral gel) Sr.no. Ingredients % 1 Carnosic acid 0.1-0.5 2 Propylene glycol 10-20 3 Triethanolamine QS 4 Carbopol 1 5 Water qs to 100 6 Curcuma longa extract (mg) 5-20 7 Punica Granatum extract ( mg) 5-20 8 Glycyrrhiza glabra extract (mg) 5-10 9 Hippophae rhamnoides extract 5-15 10 Sodium chloride 0.5-1.5 11 Calcium chloride 0.2-0.6 12 Sodium bicarbonate 1.5-2.5 13 Glycerin 8-15 14 zinc gluconate 2-8 15 Hydrolyzed corn starch 0.2-1 16 Isomalt 0.4-1 17 Flavor 0.4-1 Table 12: Dentifrice composition (Oral muco-adhesive) Sr.no. Ingredients % 1 Carnosic acid 0.1-0.5 2 Propylene glycol 10-20 3 Carbopol 934P 1 4 Curcuma longa extract (mg) 5-20 5 Punica Granatum extract ( mg) 5-20 6 Glycyrrhiza glabra extract (mg) 5-10 7 Hippophae rhamnoides extract 5-15 8 Menthe oil 1-3 9 zinc gluconate 2-8 10 Sodium benzoate 0.1-.5 11 Ethanol 30-50 12 Water 30-50 Table 13: Dentifrice composition (Oral muco-adhesive) Sr.no. Ingredients % 1 Carnosic acid 0.1-0.5 2 Propylene glycol 10-20 3 Carbopol 934P 1 4 Curcuma longa extract (mg) 5-20 5 Punica Granatum extract ( mg) 5-20 6 Glycyrrhiza glabra extract (mg) 5-10 7 Hippophae rhamnoides extract 5-15 8 Menthe oil 1-3 9 zinc gluconate 2-8 10 Sodium benzoate 0.1-.5 11 Ethanol 30-50 12 Water 30-50 13 Peptide 0.001-5 Table 14: Dentifrice composition (Oral tablets) Sr. no. Ingredients Quantity in % 1 Xylitol 8-20 2 Sodium Cocoyl Glutamate 10-20 3 Malic Acid 0.0001-0.05 4 Sorbitol 70% 5-20 5 DM Water 1-90 6 Curcuma Longa (Rhizome extract) 0.5-20 7 Arginine Hydrochloride 0.5-8 8 Sodium Bicarbonate 5-20 9 Mannitol 15-25 10 MCCP 5-10 11 Erythritol 0.5-5 12 Citric acid anhydrous 8-20 13 Potassium Nitrate 0.2-10 14 Magnesium stearate 0.01-1 15 Elettaria cardamomum (Seed 0.1-5 extract) 16 Foeniculum vulgare (Fruit extract) 0.1-5 17 Flavour 0.01-0.5 18 Melaleuca leucadendra (Leaf 0.1-5 extract) 19 Eucalyptus globules (leaf extract) 0.1-5 20 PVPK30 0.1-5 21 Sodium Saccharin 0.1-5 22 Carnosic Acid 0.1-5 23 Zinc citrate 0.1-5 24 Nano Hydroxyapatite 0.1-5 25 Propolis 0.1-5 26 Myrtus communis (Whole plant) 0.1-5 extract 27 Hippophae rhamnoides (Fruit) 0.1-5 extract 28 Syzygium aromaticum (Bulb) extract 0.1-5 29 Sodium Fluoride 0.02-0.006 30 Sodium Benzoate 0.005-0.01 Table 15: Dentifrice composition (Oral tablets) Sr. no. Ingredients Quantity in % 1 Xylitol 8-20 2 Sodium Cocoyl Glutamate 10-20 3 Malic Acid 0.0001-0.05 4 Sorbitol 70% 5-20 5 DM Water 1-90 6 Curcuma Longa (Rhizome extract) 0.5-20 7 Arginine Hydrochloride 0.5-8 8 Sodium Bicarbonate 5-20 9 Mannitol 15-25 10 MCCP 5-10 11 Erythritol 0.5-5 12 Citric acid anhydrous 8-20 13 Potassium Nitrate 0.2-10 14 Magnesium stearate 0.01-1 15 Elettaria cardamomum (Seed 0.1-5 extract) 16 Foeniculum vulgare (Fruit extract) 0.1-5 17 Flavour 0.01-0.5 18 Melaleuca leucadendra (Leaf 0.1-5 extract) 19 Eucalyptus globules (leaf extract) 0.1-5 20 PVPK30 0.1-5 21 Sodium Saccharin 0.1-5 22 Carnosic Acid 0.1-5 23 Zinc citrate 0.1-5 24 Nano Hydroxyapatite 0.1-5 25 Propolis 0.1-5 26 Myrtus communis (Whole plant) 0.1-5 extract 27 Hippophae rhamnoides (Fruit) 0.1-5 extract 28 Syzygium aromaticum (Bulb) extract 0.1-5 29 Sodium Fluoride 0.02-0.006 30 Sodium Benzoate 0.005-0.01 31 Peptide (s) 0.001-10 Table 16: Dentifrice composition (Oral spray) Sr. no. Ingredients Quantity in % 1 Xylitol 8-20 2 Sodium Cocoyl Glutamate 10-20 3 Malic Acid 0.0001-0.05 4 Sorbitol 70% 5-20 5 DM Water 1-90 6 Curcuma Longa (Rhizome extract) 0.5-20 7 Arginine Hydrochloride 0.5-8 8 Sodium Bicarbonate 5-20 9 Mannitol 15-25 10 Erythritol 0.5-5 11 Citric acid anhydrous 8-20 12 Potassium Nitrate 0.2-10 13 Elettaria cardamomum (Seed 0.1-5 extract) 14 Foeniculum vulgare (Fruit extract) 0.1-5 15 Flavour 0.01-0.5 16 Melaleuca leucadendra (Leaf 0.1-5 extract) 17 Eucalyptus globules (leaf extract) 0.1-5 18 Sodium Saccharin 0.1-5 19 Carnosic Acid 0.1-5 20 Zinc citrate 0.1-5 21 Nano Hydroxyapatite 0.1-5 22 Myrtus communis (Whole plant) 0.1-5 extract 23 Hippophae rhamnoides (Fruit) 0.1-5 extract 24 Syzygium aromaticum (Bulb) extract 0.1-5 25 Sodium Fluoride 0.02-0.006 26 Sodium Benzoate 0.005-0.01 Table 17: Dentifrice composition (Oral spray) Sr. no. Ingredients Quantity in % 1 Xylitol 8-20 2 Sodium Cocoyl Glutamate 10-20 3 Malic Acid 0.0001-0.05 4 Sorbitol 70% 5-20 5 DM Water 1-90 6 Curcuma Longa (Rhizome extract) 0.5-20 7 Arginine Hydrochloride 0.5-8 8 Sodium Bicarbonate 5-20 9 Mannitol 15-25 10 Erythritol 0.5-5 11 Citric acid anhydrous 8-20 12 Potassium Nitrate 0.2-10 13 Elettaria cardamomum (Seed 0.1-5 extract) 14 Foeniculum vulgare (Fruit extract) 0.1-5 15 Flavour 0.01-0.5 16 Melaleuca leucadendra (Leaf 0.1-5 extract) 17 Eucalyptus globules (leaf extract) 0.1-5 18 Sodium Saccharin 0.1-5 19 Carnosic Acid 0.1-5 20 Zinc citrate 0.1-5 21 Nano Hydroxyapatite 0.1-5 22 Myrtus communis (Whole plant) 0.1-5 extract 23 Hippophae rhamnoides (Fruit) 0.1-5 extract 24 Syzygium aromaticum (Bulb) extract 0.1-5 25 Sodium Fluoride 0.02-0.006 26 Sodium Benzoate 0.005-0.01 27 Peptide (s) 0.001-10 Table 18: Oral Moisturizing Gel for Dry Mouth 1 Hippophae rhamnoides (Fruit) extract 0.08 2 Curcuma Longa 0.05 3 Aloe vera 0.5 4 Calcium lactate 0.9 5 Potassium Thiocyanate 1.2 6 Sodium fluoride 0.05 7 Hydrogenated Hyaluronic acid 3 8 Glycerine 6 9 Xylitol 10 10 Propylene glycol 8 11 Xanthan gum 0.55 12 Purified water 68 13 Polysorbate 20 0.5 14 Sodium Hyaluronate 0.5 15 Genencare OSMS 0.5 16 Potassium sorbate 0.05 19 Natural peppermint flavor 0.1 20 Zinc gluconate 0.02 100 Example 2: In Vitro Study: The novel formulation promotes fluoride uptake into artificial carious lesions An outline of the study design is shown in Fig.1 Early artificial carious lesion formation (n=270) Group 2: 30 Group 7: 30 Group 3: 30 Group 8: 30 Group 4: 30 Group 9: 30 Group 5: 30 Surface microhardness Cross sectional Fluoride uptake measurement (SMH2) microhardness determination (n=10 for each group) measurement (n=150 (n=10 for each group) for each group) Solution Preparation: 10 The demineralization and remineralization solutions were prepared using protocols described previously (Ten Cate J, Duijsters P. Influence of fluoride in solution on tooth demineralization: I. Chemical-data. Caries Res 1983; 17:193–199.) The demineralization solution was used to establish artificial carious lesions from pH- cycling, and it contained 50 mM acetic acid, 2.2 mM Ca (NO3)2, 2.2 mM KH2PO4 and 15 0.1 ppm NaF (pH = 4.5). The remineralization solution used in pH cycling was artificial saliva, containing 2.20 g / L gastric mucin (Sigma Aldrich), 1.5 mM CaCl2, 0.9 mM KH2PO4, 130 mM KCl and 1 mM NaN3 (pH = 7.0). Test Agents: Test Agents used follows below: 20 Group 1. Deionized water, Group 2.2.5% arginine solution, Group 3. NaF solution (500 ppmF), Group 4. Arginine / NaF solution (2.5% arginine, 500 ppmF), Group 5. Arginine / NaF solution / Potassium Nitrate (2.5% arginine, 500 ppmF, 1.5%), Group 6. Arginine / NaF solution / Potassium Nitrate / Nano Hydroxyapatite (2.5% arginine, 500 ppmF, 1.5% Potassium Nitrate, 0.2% Nano Hydroxyapatite), Group 7. Arginine / NaF solution / Potassium Nitrate / Nano Hydroxyapatite / Curcuma Longa extract (2.5% arginine, 500 ppmF, 1.5% Potassium Nitrate, 0.2% Nano Hydroxyapatite, 7% Curcuma Longa extract. Group 8. Arginine / NaF solution / Potassium Nitrate / Nano Hydroxyapatite / Curcuma Longa extract / zinc citrate (2.5% arginine, 500 ppmF, 1.5% Potassium Nitrate, 0.2% Nano Hydroxyapatite, 7% Curcuma Longa extract,0.9% zinc citrate ). Preparation of Toothpaste Samples Toothpaste samples were prepared prior to use by mixing 20 g of toothpaste into 40 mL of deionized water under constant stirring as described in a previous study (White DJ, Featherstone JD. A longitudinal microhardness analysis of fluoride dentifrice effects on lesion progression in vitro. Caries Res 1987;21:502–512). Fluoride ion concentrations of different tooth samples were measured using a fluoride ion-specific electrode (Thermo Fisher, Pittsburgh, USA). Tooth Specimen Preparation: The human permanent molars free of white spots, cracks and other defects were collected. The teeth were stored at 4 °C in water containing 0.05% thymol prior to sample preparation. Crowns were separated from roots and then cut into four sections (approximately 4 mm X 4 mm X 3 mm) with a diamond-coated saw (Struers Minitom; Struers, Copenhagen, Denmark) under constant water cooling, resulting in an overall sample size of 320 enamel slabs (4 mm X4 mm). The enamel slabs were embedded in polymethylmethacrylate, and natural tooth surfaces were then polished progressively with water-proof SiC abrasive papers (800–2400 grit; Struers, Copenhagen, Denmark), followed by polishing on a felt cloth impregnated with 1–5 μm diamond paste. This resulted in the removal of approximately 200 μm of the outer enamel layer. The specimens were ultrasonically cleaned in a deionized water bath for 2 minutes and then visually inspected to ensure removal of surface debris before microhardness analysis was undertaken. Surface microhardness (SMH) of the sound enamel was determined with a microhardness tester (Duramin-1 / -2; Struers, Copenhagen, Denmark) by using a Knoop hardness indenter at 200 g load for 15 seconds. Five indentations spaced 100 μm apart were made on the exposed enamel surface. Enamel blocks with SMH between 300 and 400 Knoop hardness numbers (KHN) were selected for the next stage of the study. Early Carious Lesion Formation: Early artificial enamel carious lesions were established using the method described (Ten Cate J, Duijsters P. Influence of fluoride in solution on tooth demineralization: I. Chemical-data. Caries Res 1983;17:193–199. Parts of enamel specimens (4 mmX4 mm) were covered with two layers of acid-resistant nail varnish, leaving only an exposed window (3 mm X 3 mm). Each specimen was immersed in 10 mL demineralization solution for 72–96 hours at 37 °C. After artificial carious lesions were formed, the surface microhardness of enamel blocks was remeasured (SMH1). One hundred and eighty blocks with baseline KHN values (SMH1) between 35 and 55 were selected for pH-cycling. One half of the previously exposed window in each specimen was covered with nail polish to maintain the baseline lesion, leaving only an exposed window (1.5 mm X 3 mm) for 10-day pH-cycling. pH-cycling Specimens were randomly divided into treatment groups according to test agents and then subjected to pH-cycling using White’s regimen (White D. Reactivity of fluoride dentifrices with artificial caries I. Effect on early lesions. F uptake hardening and remineralisation. Caries Res 1987;21:126–140). The daily de / remineralization cycling regimen consisted of a 2 hour per day simulated plaque acid challenge in the demineralization solution between 11 am and 1 pm, followed by 4 one-minute episodes of treatment with test agents at 8 am, 9 am, 3 pm and 4 pm, respectively. All solutions were freshly prepared and used with continuous stirring at 350-500 rpm throughout the treatment period. After each treatment, the blocks were rinsed with running deionized water. The specimens were placed in remineralization solution for the rest of time during pH cycling (approximately 22 hours per day). The regimen was repeated for 10 days and the temperature was maintained at 37 °C. Post-treatment Measurement After a 10-day pH-cycling regimen, the specimens were subjected to four different types of analyses including SMH measurement (n = 8 per group), cross-sectional microhardness measurement (n = 8 per group), fluoride uptake determination (n = 8 per group), and polarized microscopy (n = 6 per group) (Fig. 1). Surface microhardness (SMH2) was measured with the same static load and time as SMH1. The change in KHN (DSMH) was determined as follows (Karlinsey RL, Mackey AC, Walker TJ, et al. In vitro remineralization of human and bovine white-spot enamel lesions by NaF dentifrices: a pilot study. J Dent Oral Hyg 2011;3:22–29) : ΔSMH1 = SMH2 – SMH1, with a positive value indicating an increase in microhardness from test agents. The specimens were then immersed in the demineralization solution to simulate plaque acid challenge for 2 hours before the third surface microhardness (SMH3) was recorded. The change in KHN, i.e. ΔSMH2 = SMH3-SMH1 reflected the resistance of remineralized enamel to further demineralization. Indentations of SMH1, SMH2 and SMH3 were made approximately 200μm apart to prevent microcrack propagation from affecting the measurements. Cross-sectional microhardness (CSMH) was tested using the protocols described (Deng M, Wen HL, Dong XL, et al. Effects of 45S5 bioglass on surface properties of dental enamel subjected to 35% hydrogen peroxide. Int J Oral Sci 2013;5:103–110). Briefly, specimens were longitudinally sectioned through the centre, and indentations were made every 20 μm from the outer enamel surface by using a Knoop hardness indenter at a 50 g load for 15 seconds. CSMH values were then converted to volume percentage mineral (volume % mineral) values as described (Featherstone J, ten Cate J, Shariati M, et al. Comparison of artificial caries-like lesions by quantitative microradiography and microhardness profiles. Caries Res 2009;17:385–391.) Volume % mineral = 4.3KHN1 / 2 + 11.3. Mineral profiles at various depths were plotted to calculate the overall relative integrated mineral recovery values (IMRV, vol. % 9 mm), from which the integrated mineral recovery values were determined for each group (White D, Featherstone J. A longitudinal microhardness analysis of fluoride dentifrice effects on lesion progression in vitro. Caries Res 2009; 21:502–512). Fluoride uptake was determined with acid etching method (Faller R, Best J, Featherstone J, et al. Anticaries efficacy of an improved stannous fluoride toothpaste. J Clin Dent 1995; 6:89– 96). The specimens were dissolved in 1 N perchloric acid (2 mL / specimen) under continuous stirring for 15 seconds, and 150 µL of total ionic strength adjustment buffer was added, before the pH of the solution was titrated to 7.0 (0.05) with 1 N sodium hydroxide. A calibrated fluoride ion-specific electrode (Thermo Fisher, Pittsburgh, PA, USA) was used to read the millivolt potential of the solution, and fluoride concentration was determined in µg F / cm2 from a calibration curve obtained on the same day of the analysis. In addition, the fluoride concentrations of six treatment solutions were measured with fluoride ion-specific electrode. For polarized microscopy, thin planoparallel sections (about 80 lm thick) were prepared from around the centre of each specimen, and then mounted on a glass slide before being examined under a polarized light microscope at 109 magnification (Eclipse ME600L, Nikon, Tokyo, Japan). Changes on lesion depth before and after remineralization were calculated by using an image analysis system (Image ProPlus version 6.0, Media Cybernetics, Inc., Silver Spring, MD, USA). An average of three different measurements was obtained from each specimen for statistical analysis. Statistical analysis: Data were analysed by using SPSS 18.0 software. Student’s paired t-tests were used to compare changes in the SMH values before and after the treatments. The changes in SMH (SMH1, SMH2, SMH3), DSMH (DSMH1, DSMH2), IMRV and lesion depths between different treatment groups were analysed by using one-way ANOVA and LSD post hoc test. The changes in volume % mineral values between different treatment groups were analysed by using two-way ANOVA (with treatment solutions and lesion depths as two independent variables), followed by post hoc Games–Howell tests for multiple comparisons. The significance level was set at 0.05. Table 19. Surface Microhardness of Enamel Samples in Different Treatment Groups (mean SD) Sr. no. Groups SMH1 SMH2 SMH3 CSMH1 CSMH2 1 Group 1 45.5(0.8) 54.6(2.2) 51.4(1.8) 9.1(1.9) 5.9(1.4) 2 Group 2 45.6(1.1) 86.8(5.1) 79.5(5.7) 41.2(5.1) 34.9(5.9) 3 Group 3 45.8(1.1) 99.2(2.3) 89.4(4.7) 52.4(4.5) 42.1(6.4) 4 Group 4 45.6(0.8) 125.7(4.6) 111(6.2) 80.1(4.9) 66.3(7.1) 5 Group 5 46.2(0.8) 160.4(9.3) 148.5(8.2) 114.2(9.5) 103.8(10.9) 6 Group 6 45.8(1.1) 181.8(3.1) 168.9(4.5) 136(3.4) 123.1(4.8) 7 Group 7 46.1(0.9) 201.5(8.9) 186.4(4.5) 155.4(9.2) 140.7(4.9) 8 Group 8 46(1.1) 219.3(5.7) 205.7(9.3) 173.3(5.6) 159.7(8.5) Data on changes in SMH after 10-day pH-cycling and 2 hour simulated plaque acid challenge (ΔSMH1 and ΔSMH2, respectively) showed the lowest remineralization efficacies for the deionized water group and the 2.5% arginine solution group (table 19). The Arginine / NaF solution / Potassium Nitrate / Nano Hydroxyapatite / Curcuma Longa extract / zinc citrate (2.5% arginine, 500 ppmF, 1.5% Potassium Nitrate, 0.2% Nano Hydroxyapatite, 7% Curcuma Longa extract,0.9% zinc citrate) toothpaste showed greatest remineralization efficacy among all treatments. The Arginine / NaF solution / Potassium Nitrate / Nano Hydroxyapatite / Curcuma Longa extract / zinc citrate (2.5% arginine, 500 ppmF, 1.5% Potassium Nitrate, 0.2% Nano Hydroxyapatite, 7% Curcuma Longa extract,0.9% zinc citrate ) toothpaste containing toothpaste slurry exhibited the greatest remineralization efficacy, with the increases in IMRV and volume % mineral being detected up to 150 µm beneath the surface compared to other test agents (table 20) Table 20. Enamel Mineral Content Values (mean SD) of the Artificial Carious Lesions After pH-cycling (n = 10) for Each Group Sr. Group 20 50 100 150 mean no. integrated mineral recovery value 1 Group 35.5(1.6) 30.5(2.2) 58.6(2.3) 84.6(2.4) 11424.8(267.3) 1 2 Group 45(10.2) 36.1(2.8) 70.7(2.0) 88.9(2.1) 13021.3(671.2) 2 3 Group 50.5(1.6) 44(2.1) 79.6(2.4) 103.3(4.4) 13160.9(184.6) 3 4 Group 63.4(2.2) 53.9(2.7) 93.6(3.4) 114.4(5.2) 13790.3(140.2) 4 5 Group 73.3(2.7) 62.7(1.9) 107.1(3.6) 132.4(5.2) 13924.1(73.1) 5 6 Group 85.1(3.5) 72.6(1.9) 125.6(5.2) 155.2(4.8) 14075.9(84.1) 6 7 Group 97.6(3.1) 83.2(3.9) 146(10.3) 172.3(6.2) 14294.7(99.5) 7 8 Group 115.8(3.4) 91(1.2) 153.8(6.1) 185.1(6.4) 14768(117.1) 8 Table 21. Inherent Fluoride Content in Each Test Agent and the Post-treatment Enamel Fluoride Uptake (mean SD) (n = 10) for Each Group Sr. no. Groups Fluoride labeled Enamel fluoride (ppm) uptake (μg / cm2) 1 Group 1 0.01 1.5(0.4) 2 Group 2 0.01 2.4(0.2) 3 Group 3 500 3.6(0.4) 4 Group 4 500 5.5(0.3) 5 Group 5 500 7.3(0.5) 6 Group 6 500 26.1(2.4) 7 Group 7 500 42.1(2.4) 8 Group 8 500 55.6 (2.9) Deionized water, arginine solution and NaF solution had no significant effect on enamel fluoride uptake, but Arginine / NaF solution / Potassium Nitrate / Nano Hydroxyapatite / Curcuma Longa extract / zinc citrate (2.5% arginine, 500 ppmF, 1.5% Potassium Nitrate, 0.2% Nano Hydroxyapatite, 7% Curcuma Longa extract,0.9% zinc citrate ) solution significantly enhanced enamel fluoride uptake compared with the other solutions (Table 21; p < 0.05). Example 3: In Vitro Anti-bacterial Activity of Toothpaste Against Dental Pathogens Different clinical isolates of bacterial strains selected for the study includes Staphylococcus aureus(S.aurues), Streptococcus mutans(S.mutans), Bacillus cereus (B. cereus), Streptococcus pyrogenes (S.pyrogenes), Streptococcus viridians (S. viridans), Staphylococcusepidermidis (S.epidermidis), and Corynebacterium xerosis (C.xerosis) gram positive bacteria and Escherichia coli (E. coli), Klebsiella pneuomoniae(K. pneuomoniae), Proteus vulgaris (P.vulgaris) and Pseudomonas aeruginosa (P.aeruginosa), P. gingivalis, T. forsythia, T. denticola, A. actinomycetemcomitans, P. intermedia, B. forsythus, C. rectus, E. nodatum, P. micros, S. intermedius gram negative bacterial strains which are responsible for causing oro-dental disease. These strains were screened for evaluation of antibacterial activities of the novel toothpaste. Nutrient Agar No.2 (NA) (M 1269S- 500G, Hi-media Labs Pvt. Ltd, Bombay, India) was used as the solid media namely for preparing nutrient plates, while Nutrient Broth (NB) (M002-500G, Hi-media Labs Pvt. Ltd, Bombay, India) was used for the preparation of liquid culture media. The antibacterial activity of the toothpaste form was evaluated by the agar well diffusion method (Barry AL, Thornsberry C. Susceptibility tests: diffusion test procedures A. Balows (Ed.), Manual of Clinical Microbiology (fifth ed.), Asm International, Boston (1991), pp. 1117-1125) . All the microbial cultures were adjusted to 0.5 McFarland standards, which is visually comparable to a microbial suspension of 1.5 Х 108cfu / ml. Autoclaved agar media (20 ml) was poured into each petri plate, followed by the swabbing of bacterial colony from the inoculums of the test microorganisms on prepared media plates, which were then incubated for 15 min at 37 °C to allow proper adsorption and active growth of the pathogen. It was followed by pouring of the test sample (100 μl reconstituted in the dimethyl sulphoxide-DMSO 0.1%) into the wells of 6 mm diameter (bored by sterile core- borer) of the seeded agar plates. Subsequently dimethyl sulphoxide-DMSO 0.1%- (the solvent used to reconstitute the test sample) was also poured to assess its activity, if any (Negative Control) and standard antibiotic disc- Ciprofloxacin 5 μg / disk (for gram positive) and Gentamicin 10 μg / disk (for gram negative) (Positive control) was placed in the same plate. All the plates were incubated at 37 °C for 24 h. After incubation the antimicrobial activity of the toothpaste form was evaluated by measuring the zone of growth inhibition against the test microorganisms with Antibiotic Zone Scale (PW297, Hi-media Labs Pvt. Ltd., Mumbai, India), which was held over the back of the inverted plate. The plate was held a few inches above a black, nonreflecting background and illuminated with reflected light. The experiments were performed in triplicate. Toothpaste in its prepared form was used for screening antibacterial activity using Kirby-Bauer's disk diffusion method and the Agar well method according to CLSI Guidelines [F.D. Gonelimali FD, Lin J, Miao W, Xuan J, Charles F, Chen M, Hatab SR. Antimicrobial properties and the mechanism of action of some plant extracts against food pathogens and spoilage microorganisms. Front. Microbiol. 2018; 9: 1639) against some clinical isolates of seven Gram positive and four Gram Negative bacterial strains. 50 μg of the test drug compound (toothpaste) was used and compared with the Positive Control 1 (Standard drug Ciprofloxacin for Gram positive and Gentamicin for Gram Negative bacteria) and positive control 2 Doxycycline Hyclate (FDA approved) and Negative / Plane control Table 22. Mean (Standard Deviation) Antibacterial Screening: Zone of Inhibition (in mm) of the Complex Against Bacterial Strains. Sr. Strains Positive Positive Negative Test Drug no. control 1 control 2 control sample 1 Gram positive strains 2 S. aureus 32.33(1.15) 30.33(0.57) 6.33(0.57) 27.33(1.15) 3 S. mutans 29.33(0.57) 30.33(0.57) 6.33 26.33(0.57) (0.57) 4 S.pyogenes 26.66(0.57) 28.66(0.57) 6.66(0.57) 20.33(0.57) 5 S. viridians 20.33(1.15) 21.33(0.57) 6.33(0.57) 16.66(0.57) 6 S.epidermis 20.33(0.57) 20.66(0.57) 6.66(0.57) 16.33(0.57) 7 C. xerosis 30.33(0.57) 32.33(0.57) 6.33(0.57) 22.33(0.57) 8 B. cereus 18.33(0.57) 20.33(0.57) 6.66(0.57) 15.33(0.57) 9 Gram Negative Strains 10 E.coli 20.33(0.57) 18.33(0.57) 6.33(0.57) 16.33(0.57) 11 K. pneuomoniae 20.33 20.33(0.57) 6.33(0.57) 22.33(0.57) (0.57) 12 P. aruginosa 22.33(0.57) 20.33(0.57) 6.66(0.57) 20.33(0.57) 13 P. vulgaris 20.33(0.57) 21.33(0.57) 6.33(0.57) 18.33(0.57) 14 P. gingivalis 15.66(1.15) 20.33(0.57) 6.66(0.57) 16.33(0.57) 15 T. forsythia 18.33(0.57) 20.33(1.15) 6.33(0.57) 15.66(0.57) 16 T. denticola 22.33 22.33(0.57) 6.33(0.57) 17.33(0.57) (0.57) 17 A. 20.33(0.57) 24.66(0.57) 6.66(0.57) 16.33(0.57) actinomycetemcomitans 18 P. intermedia 20.66(1.15) 26.33(1.15) 6.33(0.57) 20.33(0.57) 19 B. forsythus 18.33(0.57) 24.33(0.57) 6.33(0.57) 20.33(0.57) 20 C. rectus 20.66(0.57) 26.33(0.57) 6.66(0.57) 22.33(0.57) 21 E. nodatum 19.33(0.57) 26.33(0.57) 6.33(0.57) 18.33(0.57) 22 P. micros 20.33(0.57) 24.33(1.15) 6.66(0.57) 20.33(0.57) 23 S. intermedius 22.66(0.57) 26.33(0.57) 6.33(0.57) 22.33(0.57) Zone of inhibition of positive control 2 against bacterial strains was non significantly higher compared to positive control 1 and the test drug sample, however the zone of inhibition of the test drug sample was comparable to positive control 1 and 2 (Table 22 ) Example 4: The Novel Formulation Attenuates the Pathogenic Properties of Porphyromonas Gingivalis and Protects Gingival Keratinocyte Barrier Function in an In Vitro Model The Novel toothpaste formulation and BioMinF© dentifrice were used at dilutions of 1 / 500, 1 / 1000, and 1 / 2000 (w / v). When the Novel toothpaste and BioMinF© dentifrice were inoculated onto Todd-Hewitt agar plates (THA; Becton, Dickinson and Company, Sparks, MD, USA), no microbial contamination was observed. P. gingivalis ATCC 33277 was grown in an anaerobic chamber for 24 h at 35° C in Todd- Hewitt broth supplemented with 0.001% (w / v) hemin and 0.0001% (w / v) vitamin K (THB-HK) Hemolytic Assay: Fresh sheep red blood cells (Nutri-Bact, Canada) were harvested from heparinized whole blood by centrifugation (1000 x g for 4 min), washed three times in phosphate-buffered saline (PBS; pH 6.8), and suspended in PBS to a concentration of 2% (v / v). Equal volumes (1 ml) of red blood cells, P. gingivalis cells (optical density at 660 nm [OD660] = 1.0 in PBS), and two-fold serial dilutions of the Novel toothpaste and BioMinF© dentifrice were mixed together. PBS replaced the bacteria in the negative control. Following an incubation at 37°C for 200 minutes, the mixtures were incubated at 4°C for 60 minutes and were then centrifuged (12000 x g for 5 min) prior to recording the absorbance of the supernatants at 540 nm (A540). Proteolytic Assay: To determine the effects of the Novel toothpaste and BioMinF© dentifrice on the proteinase activity of P. gingivalis, a 48-h culture was centrifuged at 10000 x g for 10 min and the supernatant was collected. Assay mixtures containing equal volumes of P. gingivalis culture supernatant, the fluorescent substrate collagen DQTM (100 µg / ml; Molecular Probes, Eugene, OR, USA), and the Novel toothpaste and BioMinF© dentifrice were prepared and incubated for 2 h at 37°C. The fluorescence corresponding to collagen degradation was monitored at time 0, 30, 60, 90, and 120 min using a Synergy 2 microplate reader (BioTek Instruments, USA), with the excitation and emission wavelengths set at 495 nm and 525 nm, respectively. Test compounds or the fluorescent substrate alone were used as controls. Leupeptin (1 µM) was used as a positive inhibitory control. Assays were performed in triplicate in two independent experiments and the means ± SD were calculated. Human Gingival Keratinocyte Culture: The human gingival keratinocyte cell line was used to investigate the effects of the Novel toothpaste and the BioMinF© dentifrice on keratinocyte barrier integrity. Keratinocytes were cultivated in keratinocyte serum-free medium (K-SFM; Life Technologies Inc., Burlington, ON, Canada) supplemented with growth factors (50 µg / ml of bovine pituitary extract and 5 ng / ml of human epidermal growth factor) and 100 µg / ml of penicillin G-streptomycin at 37°C in a 5% CO2 atmosphere. Transepithelial Electrical Resistance Assay: The tight junction integrity of the B11 gingival keratinocyte barrier was assessed by determining the transepithelial electrical resistance (TER) using the procedure of Gunbiner B and Simons K. (A functional assay for proteins involved in establishing an epithelial occludin barrier: identification of a uvomorulin-like polypeptide. J Cell Biol. 1986;102:457–468). Paracellular Permeability Assay: The ability of the test compounds to enhance or protect gingival keratinocyte barrier integrity was further assessed by monitoring the paracellular transport of fluorescein isothiocyanate (FITC)- conjugated 4.4-kDa dextran (FD-4; Sigma-Aldrich Canada Co., Oakville, ON, Canada) across the keratinocyte layer. Briefly, B11 cells were cultured on Transwell™ filters, and FD-4 (1 mg / ml in culture medium) was added to the apical compartment in the presence of the test compounds. The presence of FD-4 in the basolateral compartment was determined at 0, 2, 6, 24, and 48 h by measuring the fluorescence (relative fluorescence units [RFU]; excitation wavelength 495 nm; emission wavelength 525 nm) using a Synergy 2 microplate reader. The effects of P. gingivalis (MOI = 104) on paracellular permeability and the protective effects of the Novel toothpaste and the BioMinF© dentifrice were assessed under the conditions described. Statistical analyses were performed using a one-way analysis of variance with a post hoc Bonferroni multiple comparison test (GraphPad Software Inc., La Jolla, CA, USA). All results were considered statistically significant at p< 0.05 Results: Table 23: P. Gingivalis Cells Caused Marked Hemolysis of Sheep Red Blood Cells in a Hemolytic Assay Sr.no. Compounds Dilution Relative Hemolysis (%) 1 Novel formulation 1 / 500 50.5(1.5) 1 / 1000 52.5(0.5) 1 / 2000 55.5(1.0) 1 / 4000 56.5(0.5) 1 / 8000 58.5(1.0) 1 / 16000 60.0(0.5) 2 BioMinF© 1 / 500 110.5(0.5) 1 / 1000 112.5(1.0) 1 / 2000 100.5(1.5) 1 / 4000 98.5(0.5) 1 / 8000 105.5(1.5) 1 / 16000 95.5(1.5) The Novel formulation significantly reduced hemolysis (Table 23). BioMinF© did not inhibit the hemolysis caused by P. gingivalis. We then investigated the ability of the Novel formulation to inhibit the degradation of type I collagen by proteinases present in a culture supernatant of P. gingivalis. Significant time- and dose- dependent inhibition was observed with both the Novel formulation and the BioMinF© technology. More specifically, at the lowest dilution tested (1 / 500) and after a 2-h incubation, the Novel formulation caused a 50% inhibition of type I collagen degradation. BioMinF© reduced collagen degradation by 20%. After investigating the effects of the Novel formulation on P. gingivalis, its ability to promote gingival keratinocyte barrier integrity was assessed. Preliminary assays showed that, at the concentrations used, the Novel formulation and the BioMinF© technology did not significantly affect the viability of gingival keratinocytes as determined using a colorimetric MTT assay. The ability of the Novel formulation to modulate the integrity of the gingival keratinocyte tight junction was determined by monitoring TER values over a period of 48 h. The Novel formulation induced a significant time-dependent increase in TER. A 24-h treatment of the keratinocytes with the 1 / 500 and 1 / 1000 dilutions of Novel formulation caused a 2.5- and 2.0-fold increase in TER, respectively, compared to untreated cells. Furthermore, the 1 / 500 and 1 / 1000 dilutions of BioMinF© caused a 1.5-and 1.0-fold increase in TER, respectively. To confirm that the Novel formulation enhanced the function of the keratinocyte barrier, the effect on paracellular permeability was investigated by measuring the apical-to-basolateral transport of FD-4. The paracellular transport of FD-4 time-dependently increased in the control assay (compounds). However, in the presence of the Novel formulation, the increase in FD-4 transport through the gingival keratinocyte barrier was significantly attenuated. More specifically, following a 24-h treatment, the Novel formulation at the lowest dilution tested (1 / 500) reduced FD-4 transport by 49.0%, while the BioMinF© only reduced FD-4 transport through the barrier model by 15.8%. We then examined the effect of the 1 / 500 and 1 / 1000 dilutions of the Novel formulation on the distribution of two junction proteins (ZO-1 and occludin) by immunofluorescence. Both the aqueous solution and dentifrice increased the immunolabeling of ZO-1 and occludin in the areas of cell-cell contact, while the BioMinF© technology had little or no effect on the immunolabeling of ZO-1 and occludin. Since P. gingivalis may have a deleterious effect on keratinocyte barrier integrity, we investigated whether the Novel formulation protects gingival keratinocytes from damage. Treating the keratinocytes with P. gingivalis at an MOI of 104 significantly decreased TER. After 24- and 48-h incubations, P. gingivalis decreased TER by 90%. Despite the effect of P. gingivalis on barrier integrity, it should be noted that no significant loss of cell viability was observed using a MTT assay that determines cell metabolic activity. We then examined the protective effect of the Novel formulation on TER when the keratinocytes were challenged with P. gingivalis. Here the Novel formulation attenuated the P. gingivalis-mediated loss of keratinocyte barrier integrity. More specifically, following a 48-h incubation, a 1 / 500 dilution of the Novel formulation reduced the ability of P. gingivalis to decrease TER 20-fold. A 1 / 500 dilution of BioMinF© provided a protective effect, reducing P. gingivalis-induced damage by a factor of 10-fold. Conclusions: The Novel formulation may offer benefits for patients affected by periodontal disease through its ability to attenuate the pathogenic properties of P. gingivalis and promote keratinocyte barrier function Example 5: In Vitro Dentine Tubule Occlusion by the Novel Toothpaste Ethical clearance was obtained from the Scientific Research Unit of the institute, India and all the ethical protocols were strictly followed. Composition of Dentifrices: StarBright™ 5% Sodium Fluoride Varnish, (Nanova USA), BioMinF© were used in this study for the purpose of comparison with the new dentifrice (Jasmate ®TM) . Preparation of Dentin Discs and Grouping of Specimens: For this study, extracted Surgery Clinics of the Institute (Rohtak, India). A total of 40 dentin discs of 2.0 mm (± 0.2 mm) size were prepared by cutting each tooth horizontally (mesio-distally) over the cemento- enamel junction, utilizing a cooled diamond saw (Isomet® 5000 Linear Precision Saw, Buehler Ltd., Lake Bluff, IL, USA). The occlusal enamel, 2.5 mm down the cusp tip, was also removed and the teeth were cut mesio-distally. The upper surfaces of the dentin discs were marked, and the unmarked surfaces were etched with 37% orthophosphoric acid for 20 seconds to open the tubules and to free them from any organic material. Post-etching, the discs were washed with distilled water for 1 min and randomly divided into the following three groups, each group receiving 10 discs, based on their treatment with different dentifrices: Group 1 (n=10) = discs brushed with artificial saliva (control); Group 2 (n=10) = discs brushed with fluoride dentifrice (StarBright™ 5% Sodium Fluoride Varnish, Nanova Biomaterials, Inc, USA); Group 3 (n=10) = discs treated with BioMinF©; Group 4 (n=10) = discs treated with Zecmate™ (Novel formulation). The control group formulation was prepared by mixing the following chemicals in 1,000 mL of deionized water, as proposed by Fusayama et al. (Usayama T, Katayori T, Nomoto S. Corrosion of gold and amalgam placed in contact with each other. J Dent Res.1963 Sep-Oct; 42(5):1183–97.): NaCl: 0.400 g, KCl: 0.400 g, NaH2PO4. H2O: 0.69 g; CaCl2. H2O: 0.795 g; Na2S. 9H2O: 0.005 g. The pH of the freshly prepared saliva sample was 5.5, which was adjusted to the neutral pH of 7.0 by adding aliquots of NaOH (Usayama T, Katayori T, Nomoto S. Corrosion of gold and amalgam placed in contact with each other. J Dent Res.1963 Sep-Oct; 42(5):1183–97.) The discs were subjected to a pre-treatment SEM analysis. Each treatment group dentine disc specimen was treated with the respective slurry for two minutes for a period of seven days (Yuan P, Shen X, Liu J, Hou Y, Zhu M, Huang J, et al. Effects of dentifrice containing hydroxyapatite on dentinal tubule occlusion and aqueous hexavalent chromium cations sorption: A preliminary study. PLoS ONE. 2012;7(12):e45283). Subsequent to this treatment, the specimens were dried and prepared for analysis by SEM. After drying, the discs were mounted onto aluminium stubs and subsequently coated with a thin layer of gold / palladium in a sputter coater. Photographs of the samples were obtained from the camera which was fixed to the SEM. The surface of the samples were scanned and examined using SEM (JEOL Model 5400, JEOL Co., Tokyo, Japan) at 1000X and 20kV. The total number of tubules, open tubules, completely occluded tubules and partially occluded tubules were calculated in each image of all of the samples. The number of tubules evident in each of the 1000X images was counted to provide a measure of tubule occlusion efficacy. Both the fully-open tubules and the partially- open tubules were included in the count. Table 24: Completely Occluded Tubules and Comparison of the Efficacy of (Novel formulation) Jasmate®TM, BioMin® F and StarBright™ 5% Sodium Fluoride Varnish in Occluding Tubules. Before After 7 days Number Analysis treatment (Number of closed (number of of open dentinal open dentinal dentinal tubules tubules) tubules) after Mean (S.D) Mean (S.D) treatment Mean (S.D) (Novel 136.8(14.2) 20.2(12.6) 115.5(3.6) P= 0.2792, formulation) t = 1.1259,df = Jasmate® 14, Standard error of difference = 11.902 BioMin®F 135.6(14.2) 20.6(13.6) 114.2(5.6) StarBright™ 5% 138.2(16.8) 24.4(12.2) 113.8(4.8) Sodium Fluoride Varnish StarBright™ 5% Sodium Fluoride varnish, BioMin® F and (Novel formulation) Jasmate®TMtoothpaste were capable of achieving dentinal tubule occlusion. There was no statistical significant difference between the groups StarBright™ 5% Sodium Fluoride varnish, BioMin® F and Jasmate® toothpaste (p=0.279, 0.434, Table 24). So, Jasmate®TMNovel formulation is substantial equivalent to BioMin® F and the StarBright™ 5% Sodium Fluoride varnish and Jasmate®TM(Novel formulation) toothpaste in effective in dentine tubule occlusion. Example 6: Bench Testing and Stability Studies of novel formulation The toothpaste formulation was subjected to stability testing prior to antibacterial analysis. The stability testing aims to ensure that the mouthwash formulation is usable and can maintain the same characteristics over a long period of time, before undergoing antibacterial assay. The physical stability testing are included recording the visual appearance, physical separation, and homogeneity of the formulated toothpaste. In addition, pH stability was also monitored using a well-calibrated pH meter. To investigate the changes and variability in the pH readings, the mean and the standard deviation for the pH readings were calculated. The toothpaste formulation was kept on the shelf at 25ºC ±2ºC / 60% ± RH, 35ºC ±2ºC / 65% ± RH and 40ºC ±2ºC / 75% ± RH. The results were recorded and compared over the course of twelve weeks (Chiedozie EI, Ahamefule OF, Ukamaka AA. Anti-inflammatory, antimicrobial and stability studies of poly-herbal mouthwashes against Streptococcus mutans. J.Pharmacognosy and Phytochemistry.2016; 5(5): 354-36). Table 25: The Mean and Standard Deviation of the pH Readings of the Toothpaste Formulation Stora Baseli 1 2 3 4 5 6 7 8 9m 10 11 12 ge ne mo mo mo mo mo mo mo mo o mo mo mo 25ºC 5.9 5.9 5.9 5.9 5.9 5.9 5.9 5.8 5.8 5.8 5.8 5.8 5.8(0 ±2ºC (0.1) (0. (0. (0. (0. (0. (0. (0. (0. (0. (0.2 (0.2 .1) / 60% 1) 2) 1) 1) 2) 1) 2) 1) 2) ) ) ± RH 35ºC 5.9(0. 5.9 5.8 5.8 5.8 5.8 5.9 5.8 5.8 5.8 5.8 5.8 5.8 ±2ºC 2) (0. (0. (0. (0. (0. (0. (0. (0. (0. (0.1 (0.2 (0.1) / 65% 1) 2) 1) 2) 2) 1) 2) 1) 2) ) ) ± RH 40ºC 5.8(0. 5.9 5.9 6.0 5.9 6.0 6.0 6.0 6.0 6.0 6.0 6.1 6.1 ±2ºC 2) (0. (0. (0. (0. (0. (0. (0. (0. (0. (0.2 (0.1 (0.1) / 75% 1) 2) 2) 2) 1) 1) 2) 1) 2) ) ) ± RH 4 5.9(0. 6.0 6.0 6.0 6.0 6.0 6.0 6.0 6.0 6.0 6.0 6.1 6.0 °C±2º 1) (0. (0. (0. (0. (0. (0. (0. (0. (0. (0.2 (0.2 (0.2) C / 1) 1) 1) 2) 1) 1) 1) 2) 2) ) ) 60% ± RH The toothpaste formulation had consistent pH values with no significant change in the pH over time. From our data the toothpaste formulation is stable for up to 2 years ( table :25). Example 7: Anti-cancer testing of the novel formulation Cell Lines To examine the effects of the present composition extract of novel formulation on inhibition of cancer / tumor cells, various human cell lines were used including one normal cell line and eight cancer / tumor cell lines: 1. RPTEC (Cambrex): Normal renal proxima tubule epithelial cell, Human 2. A-498 (ATCC HTB-44): Kidney carcinoma, Human 3. HCT 116 (ATCC CCL-247): Colorectal carcinoma, Human 4. Hep 3B (ATCC HB-8064): Hepatocellular carcinoma, Human 5. LNCap clone FGC (ATCC CRL-1740): Prostate carcinoma, Human 6. MCF-7 (ATCC HTB-22): Mammary gland adenocarcinoma, Human 7. MKN45 (FDSC JCRB0245): Stomach carcinoma, Human 8. NCI-H226 (ATCC CRL-5826): Lung carcinoma, Human 9. NPC-TW01 (School of Medicine, NTU): Oral-Nasal- pharyngeal carcinoma, Human 10. KB: Oral cancer All of the cell lines used were negative for mycoplasma test. Among these cell lines, RPTEC, the only normal cell line was maintained in REGM™ Bullet Kit at 37° C in a humidified atmosphere of 5% CO 2 / 95% air, in the absence of antibiotics according to the manufacture's recommendation. On the other hand, the eight tumor cell lines were maintained in DulBeccco's modified essential medium (DMEM) supplied with 10% fetal bovine serum at 37° C., in a humidified atmosphere of 5% CO 2 / 95% air in the absence of antibiotics. Reagents Fetal calf serum was purchased from Bio Whittaker (Walkersville, Md.), MTS was obtained from Promega (Madison, Wis.). All of the other chemicals were from Sigma Chemical (St. Louis, Mo.) and were standard analytic grade or higher. Novel formulation was dissolved in the complete culture medium at final concentration of 10mg / ml and was filter sterilized. Doxorubicin and Taxol were prepared in DMSO at concentration of 20 mM and were used as the positive controls. To evaluate the anti-tumoral activity of novel formulation : Various human cancer cell lines was used to measure the potential cytotoxicity of novel formulation towards the NPC-TW01 and in vitro cytotoxicity assay was carried out. Tumor cells were seeded at a density of 2×103 to 8×103 cells / well in 96-well plate 16 hours prior to the chemicals treatment. After exposure to different concentrations of extract of novel formulation (5.0 to 16.0 mg / ml), Doxorubixin (10 μM to 3.2 nM) or Taxol (2 μM to 0.02 nM) for 72 hours, cells were washed, replaced with medium containing 0.4mg / MTS [3-(4,5-dimethythiazol-2-yl)-5-(3-carboxymethosyphenyl)-2- (4sulfophenyl)-2H-tetrazolium] and further incubated for 2 hours. To quantify the metabolically viable cells, the conversion of MTS to formazan was measured by absorbance at 490 nm in a 96-well microtiter plate reader. The mock-treated control was used to evaluate the effect of the chemical on cell growth and to determine the concentration of chemical that inhibited 50% of cell growth (IC 50 ). The percentage of cytostasis was calculated by the formula: Cytostasis(%)=[1−(B / A)]×100, where A is the absorbance of the untreated control and B is the absorbance of the treated cell. To evaluate the effects of the tested drugs on cell growth, the concentration of chemical that caused 50% reduction of the treated cells (IC 50 ) was calculated from the dose response curve for each cell line. The IC 50 for both Doxorubicin and Taxol to various human tumor cellines were found between 800 to 11 nM and 11 to 0.003 nM respectively. Our data showed that the cytotoxicity of novel formulation toward cancer cell line depends on the nature of the tumor cells, showing the selectivity of novel formulation. Among all the tumor cell lines tested, novel formulation was found to be most sensitive to KB, RPTEC, A-498, HCT 116, Hep 3B, LNCap clone FGC, MCF-7, MKN45, NCI-H226 and NPC-TW01 , as the concentration of novel formulation as low as 0.25 mg / ml was able to cause 50% reduction of the treated cells, demonstrating the efficient anti-tumor activity of novel formulation on KB, RPTEC, A-498, HCT 116, Hep 3B, LNCap clone FGC, MCF-7, MKN45, NCI-H226 and NPC-TW01. In addition, cell growth stimulation was found when KB, RPTEC, A-498, HCT 116, Hep 3B, LNCap clone FGC, MCF-7, MKN45, NCI-H226 and NPC-TW01 was cultured in higher concentration of novel formulation. The results showed that novel formulation has little or no toxicity to the normal cells and also further increase of concentration could inhibit growth of cancerous cell. Example 8: Novel formulation set forth in Example I and placebos were evaluated in vivo against oral leukoplakia, oral lichen planus, submucous fibrosis and Erythroplakia etc. In the patients tested, response to present mouth compositions is excellent on precancerous lesions. All diagnostic tests were evaluated for diagnosing oral pre-cancerous lesions. Each subject completed a medical and dental history questionnaire to determine the status of systemic diseases, chronic diseases, oral and dental diseases, smoking habit or alcohol and drug history. Novel formulation and placebo were given four times in a day for 5 minutes. Pain control and lesion healing were the two main clinical variables for evaluating cure of oral leukoplakia, oral lichen planus and oral submucous fibrosis. To measure pain, we used a visual scale analog ranging from 0.5 (Very mild pain) to 5 (severe pain). For healing, we measured changes in lesion size, including ulcer size from baseline, while; in oral submucous fibrosis in addition to the above variables , change in mouth opening was considered. Final outcome was confirmed by clinical examination. Clinical and histopathological examinations were conducted along with collection of serum and salivary samples prior to treatment of novel formulation. One week after clinical cure of diseases, clinical and histopathogical examinations were again performed along with collection of serum and salivary samples. Whole unstimulated saliva produced in a 5 min period ( 3ml) was collected, allowed to drain into a plastic container , and was centrifuged at 3000xg at 4 C for 5 min in order to remove bacterial and cellular debris. Saliva samples were stored at -80C until analysis. Blood was centrifuged at 1700xg for 10 min and plasma was separated. Plasma was stored at -80 C until analysis was performed. Serum and salivary IL-2, IL-1 beta, IL-6, IL-8, 8 OHdG , MDA, vitamin C and E were measured These biomarkers were selected because these are salivary biomarkers of oral cancer Results: AVERAGE Lesion size ( Placebo) - 20 Oral leukoplakia: baseline: 22.3mm (5.2) : After study: 22.4 mm (6.4) - 20 Lichen planus: baseline: 22.4mm (11.2) : After study : 22.6mm (11.4) - 22 Submocous fibrosis; 22.8 (11.4): after study 21.4 (12.6) AVERAGE pain score for patients - 20 oral leukoplakia: baseline: 4.5 (1.5): after study: 4.0(1.5) - 20 Lichen planus: baseline: 3.5(1.5): after study: 3.5(1.0) - 20 oral submoucous fibrois: 4.0 (1.5): after study 4.0 (1.0) Mouth opening only for submucous fibrosis baseline : 28.6 (5.6) : after study 28.2 (5.6) mm AVERAGE Lesion size (Novel formulation) - 50 oral leukoplakia: baseline: 22.6mm (4.0): End study: 3.5mm (1.4) - 50 Lichen planus: baseline: 24.5mm (4.5): End study: 3.5mm (1.0) - 50 Submocous fibrosis; 24.5 (4.0): End study 3.5 (1.5) AVERAGE pain score for patients - 50 oral leukoplakia: baseline: 4.0 (1.5): End study: 0.5(0.5) - 50 Lichen planus: baseline: 4.0(1.5): End study: 0.5(0.5) - 50 oral submoucous fibrois: 4.5 (1.5): End study 0.5 (0.5) Mouth opening only for submucous fibrosis Baseline : 20.4 (4.2) : End study 45.0 (4.6) mm Pain scores and size of lesion in oral leukoplakia, submucous fibrosis and lichen planus improved significantly ( P=0.0001) in Novel formulation as compared to placebo. In case of submucous fibrosis, mouth opening recovered significantly after novel formulation usage as compared to placebo. Oral leukoplakia, submucous fibrosis and lichen planus were clinically cured after 120 (12), 150(30), and 130(15) days, respectively. Serum and salivary IL-2, IL-1 beta, IL-6, IL-8, 8 OHdG and MDA levels were significantly decreased ( P=0.0001, 95% CI) , while vitamin C and E levels were significantly increased after treatment with novel formulation as compared to placebo. Example 9: To evaluate the effects of novel dentifrice (test tooth paste) on plaque and gingival health. The 50 subjects with moderate gingival inflammation (Löe and Silness Gingival Index ≥2) and pocket depths <4 were randomly assigned to brush twice daily for 21 days with the novel dentifrice test or the control dental gel. On Days 0, 7, 14 and 21, plaque levels (Quigley-Hein, Turesky Modification Plaque Index), gingival inflammation (Löe and Silness Gingival Index) and gingival bleeding (modified Sulcus Bleeding Index) were estimated by one blinded, investigator by using a pressure sensitive probe. Results: Table 26: Change in Clinical indices (SD) for Control and Test groups from Baseline on Day 7, Day 14 and Day 21. n=25 for the Test Group, and n=25 for the Control Group. Day Test group Control P-value Difference from Difference from baseline baseline Plaque Index 7 -1.56(0.45) -0.40(0.24) 0.0001 (0-5) 14 -1.78(0.44) -0.52(0.32) 0.00001 21 -1.99(0.34) -0.65(0.35) 0.0005 Modified 7 -1.20(0.23) -0.21(0.20) 0.00001 Sulcus Bleeding 14 -1.46(0.26) -0.27(0.20) 0.0001 Index (0-3) 21 -1.68(0.30) -0.32(0.24) 0.0005 Gingival Index 7 -0.70(0.20) -0.20(0.23) 0.0001 (0-3) 14 -1.25(0.32) -0.32(0.20) 0.0001 21 -1.54(0.30) -0.34(0.22) 0.0001 The three clinical indices were significantly improved in both groups and significantly lower in the test group after 7, 14 and 21 days ( Table 26). Conclusion: The novel dentifrice was provided effective plaque control and reduced gingival inflammation. Example 11: To study the effects of novel dentifrice (tooth paste) on overnight plaque re-accumulation and plaque removal In this double-blind, randomized crossover study, 20 subjects first brushed for one week with a washout toothpaste. On the evening of Day 7, prior to tooth brushing, Plaque Index (PI) was recorded, then plaque stained and photographed. Subsequently subjects were randomized to either brush with the test or the control tooth paste. After overnight plaque accumulation, PI was recorded. Plaque was stained and photographed before and after subjects brushed with the same toothpaste as the previous night. Subsequently, the process was repeated with the second toothpaste. Image J software was used to quantify plaque presence. Mean Baseline PI after seven days of brushing with the washout toothpaste measured 2.4(0.3) in test and 2.4(0.2) in control group. Mean increase in PI overnight was statistically significantly higher after the evening use of the control group 1.9 (0.2)) as compared to the test gel 0.45(0.23) ; p < 0.001). After the morning brushing on Day 8, the PI was also statistically significantly better after using the test tooth paste 0.93(0.24) vs. the control tooth paste 2.14(0.26); p < 0.005. The percentage of tooth surface that became covered by plaque overnight was significantly higher after using the control tooth paste the previous evening 22.6(2.7)% than after using the tested tooth paste the previous evening 9.8 (2.3)%; p < 0.005. After the morning brushing, the residual plaque area for the control tooth paste 10.3(2.1)% was also significantly higher than for the test tooth paste 2.5(0.4)%; p < 0.001. Conclusions: A test tooth paste more effectively reduced overnight plaque re- accumulation and achieved better plaque removal than a control dentifrice. It is to be understood that the example and embodiments described hereinabove are for the purpose of providing a description of the present invention by way of example and are not to be viewed as limiting the present invention in any way. Various modifications or changes that may be made to that described hereinabove by those of ordinary skill in the art are also contemplated by the present invention and are to be included within the spirit and purview of this application and the following claims.

Claims

AMENDED CLAIMS received by the International Bureau on June 3rd, 2025 (03.06.2025)Claims:

1. A dentifrice formulation for oral care comprising: o 0.5-8% w / w arginine hydrochloride; o 0.005-1.5% w / w sodium fluoride; o 0.2-10% w / w potassium nitrate; o 0.1-5% w / w nano-hydroxyapatite; o 0.05-20% w / w Curcuma longa extract containing 95% curcuminoids; o 0.1-5% w / w zinc salts selected from zinc oxide and zinc citrate in a ratio of 1:1, 1:10, or 10:1; and pharmaceutically acceptable inactive ingredients, o further may comprise 0.001-2% w / w of one or more peptides of 7-30 amino acid residues selected from SEQ ID NOs: 1-96, wherein the peptide(s) enhance gingival regeneration and increases the efficacy to treat oral disease. wherein the formulation provides synergistic effect in reducing dentine hypersensitivity and dental pain; enhances enamel fluoride uptake and remineralization; inhibits demineralization and overnight plaque accumulation; reduces gingival inflammation; and is effective in managing oral conditions selected from leukoplakia, lichen planus, submucous fibrosis, erythroplakia, periodontal disease, dental caries, ulcers, and xerostomia.

2. The formulation as claimed in claim 1, wherein the dentifrice composition is in the form selected from nanoparticles gel, nano emulsion, tooth gel, toothpaste, subgingival gel, oral moisturizing gel, mouth wash, mousse, foam, oral mouth spray, lozenge, oral chewable tablet, chewing gum, tooth whitening strips, floss and floss coatings, breath freshening dissolvable strips, or denture care or adhesive product.

3. The formulation as claimed in claim 1, wherein the toothpaste comprises: o Purified water: 1-90% w / w; o Calcium carbonate (toothpaste grade): 20-50% w / w; o Sodium cocoyl glutamate: 10-20% w / w; o Sorbitol (70%): 5-20% w / w; o G lyce ri n : 1-30% w / w; o Curcuma longa(rhizome extract): 0.5-20% w / w; o Arginine hydrochloride: 0.5-8% w / w; o Erythritol: 0.5-5% w / w;o Sodium saccharin: 0.1-5% w / w; o Potassium nitrate: 0.2-10% w / w; o Hydrated silica: 0.5-10% w / w; o Nano Hydroxyapatite: 0.1-5% o Sodium carboxymethyl cellulose: 0.2-2% w / w; o Additional plant extracts and excipients including Elettaria Cardamomum seed (extract): 0.1-5%, Foeniculum Vulgare (fruit) extract: 0.1-5%, Melaleuca Leucadendra (leaf) extract: 0.1-5%, Eucalyptus Globulus (leaf) extract: 0.1-5%, Aloe Barbadensis: 0.1- 5%, Carnosic Acid: 0.1-5%, Zinc Oxide: 0.1-5%, , Extract of Propolis Wax: 0.1-5%, Hippophae Rhamnoides Fruit Extract: 0.1-5%, Syzygium Aromaticum L. leaf extract: 0.1-5%, Myrtus Communis Extract: 0.1-5%, Sodium Fluoride: 0.02-0.006%, Sodium Benzoate: 0.005-0.01%, flavour 0.1-0.5%, optionally peptides 0.005-0.1%.

4. The formulation as claimed in claim 1, wherein in the form of a mouthwash comprising: o Hippophae rhamnoides extract: 0.08% w / w o Curcuma longa: 0.05% w / w o Tea tree oil: 0.06% w / w o Sodium fluoride: 0.05% w / w o Zinc acetate: 0.2% w / w o Potassium nitrate: l% w / w o Arginine: 0.3% w / w o Nano-hydroxyapatite: 0.2% w / w o Other acceptable excipients and preservatives including Sodium Benzoate in an amount of 0.1% by weight; Sodium Saccharin in an amount of 0.15% by weight; Menthol in an amount of 0.2% by weight; Mint Cool flavour in an amount of 0.2% by weight; Polysorbate 20 in an amount of 6% by weight, Sorbitol in an amount of 13% by weight, Tromethamine in an amount of 1.2% by weight, Cetylpyridinium chloride in an amount of 0.7% by weight; Colour Blue in an amount of 0.01% by weight; Water; q.s.to 100% by weight.

5. The formulation as claimed in claim 1, wherein the formulation is an oral moisturizing gel comprising: o Hippophae rhamnoides (Fruit) extract 0.08% w / w, o Curcuma longa extract: 0.05% w / w o Sodium fluoride: 0.05% w / wo Zinc gluconate: 0.02% w / w o Arginine hydrochloride and potassium nitrate within claimed ranges o Other moisturizing and gelling agents including Aloe vera 0.5%, Calcium lactate 0.9%, Potassium Thiocyanate 1.2%, Hydrogenated Hyaluronic acid 3%, Glycerine 6%, Xylitol 10%, Propylene glycol 8%, Xanthan gum 0.55%, Purified water 68%, Polysorbate 20 0.5%, Sodium Hyaluronate 0.5%, Genencare OSMS 0.5%, Potassium sorbate 0.05%, Natural peppermint flavor 0.1%.

6. The formulation as claimed in claim 1, wherein in the form of an oral tablet comprising: o Arginine hydrochloride: 0.5-8% w / w o Potassium nitrate: 0.2-10% w / w o Curcuma longa extract: 0.5-20% w / w o Zinc citrate: 0.1-5% w / w o Nano-hydroxyapatite: 0.1-5% w / w o Inactive excipients and binders including Xylitol 8-20%, Sodium Cocoyl Glutamate 10-20%, Malic Acid 0.0001-0.05%, Sorbitol 70% 5-20%, DM Water 1-90% , Sodium Bicarbonate 5-20%, Mannitol 15-25%, MCCP 5-10%, Erythritol 0.5-5%, Citric acid anhydrous 8- 20%, Magnesium stearate 0.01-1%, Elettaria cardamomum (Seed extract) 0.1-5%, Foeniculum vulgare (Fruit extract) 0.1-5%, Flavour 0.01-0.5%, Melaleuca leucadendra (Leaf extract) 0.1-5%, Eucalyptus globules (leaf extract) 0.1-5%, PVPK300.1-5, Sodium Saccharin 0.1-5%, Carnosic Acid 0.1-5%, Zinc citrate 0.1-5%, Propolis 0.1-5%, Myrtus communis (Whole plant) extract 0.1-5%, Hippophae rhamnoides (Fruit) extract 0.1-5%, Syzygium aromaticum (Bulb) extract 0.1-5%, Sodium Fluoride 0.02-0.006%, Sodium Benzoate 0.005-0.01%.

7. The formulation as claimed in claim 1, wherein in the form of oral spray comprising ingredients including those in claim 1 within the claimed ranges, along with flavorants and propellants including Xylitol 8-20%,Sodium Cocoyl Glutamate 10-20%, Malic Acid 0.0001-0.05%, Sorbitol 70% in 5-20%, DM Water 1-90%, Sodium Bicarbonate 5-20%, Mannitol 15- 25%, Erythritol 0.5-5%, Citric acid anhydrous 8-20%, Elettaria cardamomum 0.1-5%, Foeniculum vulgare 0.1-5%, Flavour 0.01-0.5%, Melaleuca leucadendra 0.1-5%, Eucalyptus globules 0.1-5%, Sodium Saccharin 0.1-5%, Carnosic Acid 0.1-5%, Myrtus communis 0.1-5%, Hippophae rhamnoides 0.1-5%, Syzygium aromaticum 0.1-5%, Sodium Fluoride 0.02-0.006%, Sodium Benzoate 0.005-0.01%, Peptide (s) 0.001- 10%.

8. The formulation as claimed in claim 1, wherein the formulation enhances enamel fluoride uptake, demonstrates the greatest remineralisation efficacy, exhibits anti-bacterial activity against oral and dental pathogens, promotes keratinocyte barrier function, effectively occludes dentine tubules.

9. The formulation as claimed in claim 1, wherein the formulation reduces levels of IL-2, IL-1 beta, IL-6, IL-8, 8 OHdG, and MDA, and increases levels of vitamins C and E.

10. The formulation as claimed in claim 1, wherein inactive ingredients are selected from the group consisting of flavoring agents, tooth whitening agents, colorings, preservatives, fragrances, pH modifiers, calcium abrasive, water, one or more polyphosphates, humectants, surfactants, antioxidants, desensitizing agents, anti-inflammatory agents, probiotic strains, prebiotic, buffering agent, whitening agent, anti-adhesion agent, healing agent, cooling agent, anti-fungal agent, bioactive glass, plant extracts, coating agent, moisturizing agent, xylitol, erythritol, sorbitol and mixtures thereof.

11. The formulation as claimed in claim 1, wherein the zinc salts are microencapsulated to enhance stability and controlled release during application.

12. The formulation as claimed in claim 1, wherein the hydroxyapatite is nano-hydroxyapatite, with a particle size ranging from 20-200 nm, to enhance bioavailability and efficacy in enamel remineralization.

13. The formulation as claimed in claim 1, further comprising an additional anti-inflammatory agent selected from the group consisting of bisabolol, chamomile extract, or aloe vera extract.

14. The formulation as claimed in claim 1, wherein the potassium nitrate is present in a micronized form to enhance its ability to penetrate dentinal tubules and provide rapid relief from dentine hypersensitivity.

15. The formulation as claimed in claim 1, wherein the formulation also includes a probiotic strain selected from Lactobacillus reuteri or Streptococcus salivarius, which aids in maintaining oral microbiome balance and further reducing gingival inflammation.

16. The formulation as claimed in claim 1, wherein the formulation is pH- balanced to a range of 6.5 to 7.5 to minimize enamel erosion and optimize the stability of fluoride and other active ingredients.

17. The formulation as claimed in claim 1, wherein the formulation is effective in reducing oral malodor by neutralizing volatile sulfur compounds (VSCs).

18. The formulation as claimed in claim 1, wherein the composition further comprises an ingredient selected from xylitol, erythritol, or sorbitol, to enhance oral health by reducing the risk of dental caries and promoting saliva production.

19. The formulation as claimed in claim 1, wherein the composition is designed to provide long-lasting protection against dental caries and gingivitis for up to 24 hours post-application.

20. The formulation as claimed in claim 1, wherein the formulation is optimized for pediatric use, with a reduced concentration of active ingredients and a mild flavoring agent to enhance compliance among children.

21. The formulation as claimed in claim 1, wherein the formulation includes a mucoadhesive polymer selected from carbomers, polyvinylpyrrolidone, or hydroxypropyl methylcellulose, to enhance the retention of the active ingredients on oral tissues and prolong their therapeutic effects.

22. The formulation as claimed in claim 1, wherein the formulation contains an antioxidant selected from the group consisting of green tea extract, vitamin E (tocopherol), or resveratrol, to further protect oral tissues from oxidative stress.

23. The formulation as claimed in claim 1, wherein the composition includes a desensitizing agent such as strontium chloride, in addition to potassium nitrate, for enhanced relief from dentine hypersensitivity.

24. The formulation as claimed in claim 1, wherein the formulation includes a buffering agent such as sodium bicarbonate, to help maintain an optimal pH in the oral cavity, thereby reducing acid-induced enamel erosion.

25. The formulation as claimed in claim 1, wherein the composition includes a whitening agent such as hydrated silica, calcium carbonate, or sodium bicarbonate, to provide additional cosmetic benefits by removing surface stains on teeth.

26. The formulation as claimed in claim 1, wherein the composition includes an anti-adhesion agent such as chitosan or polyphenols, which helps to prevent bacterial adhesion to tooth surfaces, thereby reducing plaque formation.

27. The formulation as claimed in claim 1, wherein the formulation is specifically designed to promote oral wound healing by incorporating healing agents such as allantoin, hyaluronic acid, or calendula extract.

28. The formulation as claimed in claim 1, wherein the composition includes a cooling agent such as menthol, eucalyptus, or a derivative thereof, to provide a long-lasting fresh breath sensation.

29. The formulation as claimed in claim 1, wherein the formulation is in the form of a chewable tablet or lozenge, designed to release active ingredients slowly in the oral cavity for extended therapeutic action.

30. The formulation as claimed in claim 1, wherein the composition is free from synthetic surfactants such as sodium lauryl sulfate, making itsuitable for individuals with sensitive oral mucosa or conditions like canker sores.

31. The formulation as claimed in claim 1, wherein the formulation includes a prebiotic such as inulin or fructo-oligosaccharides, to support the growth of beneficial oral microbiota and reduce harmful bacterial populations.

32. The formulation as claimed in claim 1, wherein the composition includes an anti-fungal agent such as clotrimazole or miconazole, to provide additional protection against oral fungal infections such as oral thrush.

33. The formulation as claimed in claim 1, wherein the composition includes a bioactive glass, such as calcium sodium phosphosilicate, to enhance remineralization and promote the repair of enamel lesions.

34. The formulation as claimed in claim 1, wherein the composition is tailored for use in orthodontic patients, providing enhanced protection against white spot lesions and plaque buildup around braces and other dental appliances.

35. The formulation as claimed in claim 1, wherein the formulation includes a coating agent such as dimethicone or glyceryl stearate, to create a protective barrier on the teeth and gums, reducing sensitivity and promoting oral tissue healing.

36. The formulation as claimed in claim 1, wherein the formulation incorporates a taste-masking technology to improve the palatability of certain active ingredients, making the product more acceptable for users sensitive to strong flavors.

37. The formulation as claimed in claim 1, wherein the composition is designed to be biodegradable and environmentally friendly, using sustainable and natural ingredients, as well as eco-friendly packaging.

38. A kit comprising a dual-chamber packaging system for separating any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues containing inactive ingredients within the dentifrice formulation until the point of use, to prevent premature interaction and ensure optimal efficacy of each component wherein the kit includes human-readable indications for the use of the composition in managing oral conditions such as enamel remineralization or gingival inflammation and reducing plaque formation wherein the kit contains a customizable oral care formulation such that users can select the concentration of specific active ingredients based on their individual needs, such as enhanced zinc salt concentrations for antibacterial effects or increased at any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues for hypersensitivity relief and includes mixing instructions for combining components at home or in a clinical setting to create a formulation tailored to specific oral health conditions.

39. A system containing the dentifrice formulation as claimed in claim 1, in a form suitable for treating dentine hypersensitivity, enamel demineralization, and oral diseases like lichen planus and leukoplakia having optional delivery mechanisms such as a toothpaste tube, spraybottle, interdental brushes and applicator syringes for subgingival administration or lozenge designed to provide controlled release of the active ingredients and a user guide detailing to apply the product for optimal results, along with a digital platform for tracking oral health improvements over time and includes clinical documentation for dentists or healthcare professionals detailing the treatment protocol, recommended frequency of application, and expected outcomes for conditions like gingival inflammation, enamel erosion, and periodontal disease.

40. The system as claimed in claim 39, wherein in conjunction with an oral health monitoring device such as a smart toothbrush or an oral pH sensor, the system allows for real-time monitoring of oral health metrics such as plaque levels, enamel demineralization, and oral acidity and provides feedback through a connected mobile app in which dentifrice formulation is adjusted over time based on the user's oral health data, promoting personalized oral care.

41. The system as claimed in claim 39, wherein it comprises a multi-step oral care regimen, starting with a plaque-control dentifrice containing any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues, followed by brushing with the dentifrice formulation to treat dentine hypersensitivity and gingival inflammation with an optional post-brushing application of a gel containing hydroxyapatite and fluoride for enhanced enamel remineralization wherein the system includes printed or digital instructions for the correct sequence and timing of product used to maximize therapeutic benefits.

42. The system as claimed in claim 39, wherein it comprises a dual-phase dispensing mechanism for the dentifrice formulation, separating components that need to remain stable until the point of use of any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues ingredients wherein the dispensing system mixes the components as they are extruded, ensuring maximum efficacy of the formulation in treating conditions like enamel demineralization and dental caries and continues to deliver therapeutic effects over 24 hours wherein the system includes a tracking mechanism of digital or mechanical to monitor product usage and alert the user when it's time for a refill.

43. A method for treating or preventing oral conditions like dentine hypersensitivity, dental pain, plaque formation, gingival inflammation, and enamel demineralization, the method comprising:(a)applying a dentifrice formulation comprising potassium nitrate, sodium fluoride, hydroxyapatite, Curcuma longa extract, zinc salts, and one or more peptides to the oral cavity;(b)allowing the formulation to remain on the teeth for a period of at least 2 minutes to enhance enamel remineralization and protection against demineralization;(c)applying the dentifrice formulation to the gums in a massaging motion for at least 1 minute daily to reduce gingival inflammation and promote tissue healing, and(d) brushing the teeth for a period of 1-3 minutes, at least once per day, to allow the active ingredients to interact with the teeth and gingivaltissues wherein brushing after meals reduces plaque formation and inhibit bacterial growth on the tooth surfaces and gums preventing dental caries by strengthening the enamel and resisting acid attacks from bacterial activity.

44. The method as claimed in claim 43, wherein pre-rinsing the oral cavity with a dentifrice containing any two or more ingredients selected from arginine hydrochloride, sodium fluoride, potassium nitrate, hydroxyapatite, Curcuma longa extract, zinc salts and peptide(s) with length of 7 to 30 amino acid residues for 30 seconds prior to brushing to enhance plaque control and freshen breath.

45. The method as claimed in claim 43, wherein applying the dentifrice formulation using an ultrasonic toothbrush for 1-2 minutes to enhance the penetration of active ingredients into the enamel and gingival tissues, resulting in better plaque removal and gingival healing.

46. The method as claimed in claim 43, wherein the dentifrice formulation comprises peptides for gingival regeneration, and the method further comprises: applying the formulation directly to areas of gingival recession and massaging gently for 1 minute daily to promote collagen synthesis and tissue regeneration.