Dental strip for oral care

Abstract

The present invention relates to an adhesive oral film strip designed for the controlled release of sodium fluoride and other therapeutic agents to enhance oral health. The strip comprises a polymeric matrix — primarily polyvinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC), and carboxymethylcellulose (CMC) which provides mechanical integrity, controlled erosion, and sustained release of active ingredients when applied to the teeth. The invention addresses the challenges of traditional fluoride delivery methods by enabling targeted, prolonged, and customizable administration of fluoride and additional agents such as remineralization compounds, desensitizers, antimicrobials, and whitening agents. The strip may feature multilayer constructions, heterogeneous therapeutic agent distribution, and auxiliary components for improved adhesion, user compliance, and safety. The invention further encompasses methods of manufacture, application, and integration into comprehensive dental care kits, offering solutions for diverse populations and oral health needs. This innovation provides a significant advancement in preventive dentistry by improving caries prevention, enamel remineralization, and overall oral hygiene, while minimizing risks such as fluorosis and enhancing user experience.

Description

[0001] DENTAL STRIP FOR ORAL CARE

[0002] FIELD OF THE INVENTION

[0003] [1] Historically, fluoride has been administered through various means, including fluoridated drinking water, dietary sources, and dental care products, particularly toothpaste. However, concerns have arisen regarding excessive fluoride intake due to its narrow safety margin. The European Food Safety Authority (EFSA) recommends a daily fluoride intake of 0.05 to 0.07 mg / kg / day and cautions against higher doses that may lead to dental fluorosis - a condition characterized by hypomineralization resulting from excessive fluoride ingestion during tooth development.

[0004] BACKGROUND OF THE INVENTION

[0005] [2] Dental caries, commonly known as tooth decay, is one of the most prevalent infectious diseases worldwide, affecting individuals across all demographics. According to the World Health Organization (WHO), an estimated 60% to 90% of school-age children have experienced dental caries, underscoring the widespread nature of this condition. The etiology of dental caries is multifactorial, primarily involving cariogenic bacteria, frequent consumption of fermentable carbohydrates, and susceptible tooth structures that increase the risk of decay.

[0006] [3] Fluoride (F), a naturally occurring halogen, is recognized as a critical agent in the prevention of dental caries. Its primary mechanisms of action include promoting enamel remineralization, reducing enamel demineralization, and inhibiting bacterial metabolism and acid production. These properties make fluoride indispensable in oral health, especially through topical applications that increase the availability of fluoride ions in the oral cavity.

[0007] [4] Historically, fluoride has been administered through various means, including fluoridated drinking water, dietary sources, and dental care products, particularly toothpaste. However, concerns have arisen regarding excessive fluoride intake due to its narrow safety margin. The European Food Safety Authority (EFSA) recommends a daily fluoride intake of 0.05 to 0.07 mg / kg / day and cautions against higher doses that may lead to dental fluorosis — a condition characterized by hypomineralization resulting from excessive fluoride ingestion during tooth development.

[0008] [5] One of the most significant challenges in managing fluoride intake is the wide range of sources from which it is derived, resulting in cumulative exposure that can exceed safe levels. This issue is particularly pronounced in young children who may inadvertently ingest fluoride, such as by swallowing fluoridated toothpaste. Additionally, children with special healthcare needs, those from socioeconomically disadvantaged backgrounds, and individuals with specific dietary habits may be at increased risk for caries, making effective fluoride management especially important in these populations.

[0009] [6] Current preventive measures, such as fluoride varnishes, have proven effective in reducing the incidence of occlusal caries, particularly in children. These varnishes adhere to tooth surfaces and gradually release fluoride, enhancing remineralization and providing long-lasting protection against caries development. However, the clinical application of fluoride varnish requires professional supervision and may not be accessible to all individuals.

[0010] Importance of Professional Administration of High-Concentration Fluoride Strips

[0011] [7] The application of fluoride for caries prevention is a well-established practice in dental care, with significant documented benefits. However, for fluoride strips containing high concentrations of fluoride, it is essential that their application be restricted to dental professionals rather than allowing patients to use them at home. Several important reasons support this approach: High concentrations of fluoride, particularly those found in professionalgrade fluoride strips, pose a significant risk of dental fluorosis if not used correctly. Dental fluorosis can result from excessive fluoride exposure during tooth development, leading to enamel hypomineralization and aesthetic concerns. Restricting the use of high-fluoride strips to dental professionals minimizes the risk of inappropriate dosing and accidental overdose. Dentists are trained to assess each patient’ s specific needs and determine the appropriate dosage and frequency of fluoride applications.

[0012] [8] Informed Clinical Judgment: Dental professionals possess the expertise to evaluate a patient’s oral health status, risk factors for dental decay, and overall health conditions. These assessments are critical in determining whether high-concentration fluoride strips are appropriate for a patient. By ensuring that only qualified professionals administer these treatments, patients receive tailored care that considers their unique circumstances, thereby enhancing the safety and effectiveness of fluoride use.

[0013] [9] Proper Application Techniques: The effectiveness of fluoride treatments depends not only on the concentration of fluoride but also on the method of application. Dentists use specific techniques to maximize efficacy while minimizing side effects. For example, proper isolation of teeth and careful monitoring during application can prevent accidental swallowing and ensure optimal fluoride retention on the tooth surface. Patients applying strips themselves may lack the necessary knowledge and skills to achieve the same level of care.

[0014]

[0010] Monitoring and Follow-Up: Professional administration allows dentists to monitor patients for adverse effects more effectively. High fluoride concentrations require careful observation, especially in vulnerable populations such as children or individuals with specific health conditions. Dentists can provide immediate guidance, support, and adjustments to treatment plans if any issues arise, ensuring a safer experience for the patient.

[0015]

[0011] Education on Fluoride Use: Dental professionals not only administer fluoride treatments but also educate patients on the importance of oral care practices. This education includes proper use of fluoride, dietary considerations, and comprehensive preventive strategies to minimize the risk of dental caries. By limiting high-concentration fluoride applications to dental professionals, patients receive appropriate education on safe fluoride use along with follow-up care.

[0016]

[0012] Potential for Inappropriate Use: Allowing patients to apply high-concentration fluoride strips without professional supervision increases the risk of inappropriate usage. Patients may be unaware of the importance of timing, the amount of fluoride applied, and potential interactions with other dental products, which could lead to excessive fluoride intake. Professional oversight ensures the integrity of the treatment process is maintained.

[0017]

[0013] Legal and Ethical Considerations: Dentists are bound by ethical and legal responsibilities to provide care in the best interests of their patients. Therefore, restricting the administration of high-concentration fluoride strips to dental professionals is essential for ensuring patient safety, treatment efficacy, and optimal oral health outcomes. Through professional oversight, patients benefit from careful assessment, proper application techniques, and ongoing support, reducing the risks associated with fluoride exposure while maximizing the protective effects against dental caries.

[0018]

[0014] Restricting the administration of high-concentration fluoride strips to dental professionals is essential to ensure patient safety, treatment efficacy, and optimal oral health outcomes. Professional oversight provides patients with careful assessment, proper application techniques, and ongoing support, reducing the risks associated with fluoride exposure while maximizing its protective effects against dental caries.

[0019] Importance of Having Fluoride on Dental Strips

[0015] The integration of fluoride into dental strips offers several critical advantages that enhance oral health, particularly in the prevention and management of dental caries. These benefits are grounded in scientific research and clinical practice and address some of the significant challenges associated with traditional fluoride delivery methods.

[0020]

[0016] Targeted Delivery and Improved Bioavailability: Dental strips infused with fluoride allow for targeted delivery of fluoride ions directly to tooth surfaces. This localized approach enhances the bioavailability of fluoride, optimizing concentrations at the site of application. Studies indicate that topical fluoride applications significantly increase fluoride concentrations in saliva and dental plaque, facilitating the formation of fluorapatite, a more acid-resistant form of hydroxyapatite that enhances enamel strength and resilience against demineralization.

[0021]

[0017] Sustained Low-Level Fluoride Release: Research has demonstrated that maintaining low-level fluoride concentrations (e.g., 0.01% to 0.1%) in the oral environment over an extended period is crucial for effective caries prevention. Traditional fluoride delivery methods typically have short fluoride retention times, requiring frequent applications to achieve similar effects. However, high-dose fluoride administration can increase the risk of dental fluorosis, especially in young children. In contrast, fluoride dental strips can provide a continuous and sustained release of fluoride, which minimizes the risk of fluorosis while delivering the protective benefits of fluoride effectively.

[0022]

[0018] Reduction in Caries Incidence: Fluoride has proven to be a powerful agent in reducing the incidence of dental caries, particularly in high-risk populations. According to the Centers for Disease Control and Prevention (CDC), fluoride varnish applied professionally can lower the risk of caries in children substantially. By incorporating fluoride into dental strips, a practical and effective means to provide consistent fluoride treatment can be achieved, particularly for children who may not regularly receive professional dental care.

[0023]

[0019] Ease of Application and Compliance: Dental strips provide a user-friendly, comfortable application method compared to traditional fluoride varnishes or gels that require professional application. Fluoride varnish, which typically contains high concentrations (around 5%), is often applied by dental professionals using an arch fluoride tray, making it less accessible for daily use at home. This convenience increases patient compliance, especially among children who may be reluctant to undergo more invasive treatments. Parents can easily administer the strips at home, ensuring that fluoride reaches the teeth consistently and effectively.

[0024]

[0020] Minimized Risk of Excessive Fluoride Exposure: Given the concerns surrounding fluoride intake, especially for young children, dental strips allow for controlled dosing of fluoride. Each strip can be formulated to deliver a precise amount of fluoride, reducing the risk of accidental overdose from other fluoride sources, like toothpaste or drinking water. This tailored approach aligns with the EFSA recommendations regarding fluoride intake and helps prevent conditions such as dental fluorosis, which can arise from excessive fluoride exposure during tooth development.

[0025]

[0021] Enhanced Remineralization and Antibacterial Properties: Fluoride promotes the remineralization of early carious lesions and strengthens the enamel. By ensuring that fluoride is readily available through dental strips, the process of remineralization can be enhanced effectively. Studies have shown that sodium fluoride strips composed of polypropylene carbonate) (PPC) exhibit excellent remineralization and antibacterial potential when fluoride content reaches up to 5%. In vitro studies have indicated that fluoride release from PPC strips occurs in a sustained manner, with approximately 100% of fluoride ions released over a 24- day period without an initial burst release. This controlled release enhances the potential for long-term anticaries effects with minimal side effects.

[0026]

[0022] Addressing Oral Health Disparities: Dental caries disproportionately affect certain demographics, including low-income and minority populations. The introduction of fluoride- infused dental strips provides a simple, effective solution that not only empowers individuals but also tackles systemic health inequities. Accessible fluoride delivery through strips can help bridge the gap in oral health disparities, ensuring more uniform preventive care across diverse populations.

[0027]

[0023] Support for Integrated Care Approaches: The development of fluoride-infused dental strips allows for additional innovations, including the potential incorporation of other preventive agents, such as antibacterial compounds. This multifaceted approach can provide comprehensive oral care solutions while also mitigating the risk associated with traditional fluoride varnish application, which necessitates professional oversight and potentially exposes patients to higher fluoride concentrations at once.

[0028]

[0024] In summary, the inclusion of fluoride in dental strips represents a significant advancement in preventive oral care. This innovative delivery system not only provides an effective means to combat dental caries but also improves accessibility, compliance, and safety while addressing public health challenges related to oral disease. By leveraging the well -documented benefits of fluoride and adapting it to modem delivery methods, fluoride dental strips hold great promise for enhancing oral health outcomes across various populations, especially in light of their ability to provide sustained, low-level fluoride exposure that minimizes the risk of dental fluorosis. SUMMARY OF THE INVENTION

[0029]

[0025] It is thus within the scope of the present invention to disclose an adhesive oral film strip for the controlled release of sodium fluoride. The strip comprises a polymeric matrix consisting essentially of a combination of polyvinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC), and carboxymethylcellulose (CMC); sodium fluoride uniformly dispersed within the polymeric matrix as an active agent; wherein the film strip has a thickness of about 80 to 150 micrometers, and wherein said polymeric combination provides mechanical integrity, controlled erosion in the oral cavity, and sustained release of sodium fluoride when applied to the teeth.

[0030]

[0026] This dental strip system facilitates a controlled release pattern for NaF, utilizing the characteristics of PVA, CMC, and HPMC polymers to achieve a release mode aligned with the gradual erosion of the polymer matrix. This method of NaF distribution significantly minimizes the initial burst release commonly associated with diffusion-based delivery systems. The strip comprises a matrix containing polyvinyl alcohol (PVA), carboxymethyl cellulose (CMC), and hydroxypropyl methyl cellulose (HPMC), which collectively function as the primary filmforming and dissolvable agents.

[0031]

[0027] Another object of the invention is to disclose a strip as defined above, wherein the strip comprises a surface. The surface is characterized by a non-diffusion release pattern of the fluorine that it comprises both: wherein said formulation for enhanced drug delivery in dental care is dissolved in a non-diffusion manner and wherein said formulation comprises: NaF as an active ingredient, Polyvinyl alcohol (PVA) as a film-forming polymer, Carboxymethyl cellulose (CMC) as a mucoadhesive, and Hydroxypropyl methyl cellulose (HPMC) as a film strength and dissolution enhancer, and optionally, glycerin, approximately 10% w / w of total polymers, as a plasticizer, propylene glycol, optionally replaced by glycerol, as a co-plasticizer, sucralose or stevia as a sweetener, Xylitol as a sweetener and anti-cavity agent, Mint or spearmint for flavor enhancement, Polysorbate 80 as a surfactant, Citric acid and trisodium citrate as pH adjusters, Sodium benzoate as a preservative, and deionized water as a solvent.

[0032]

[0028] Another object of the invention is to disclose a method of dental treatment and oral care, comprising steps of administering a strip as defined in any of the above on or adjacent to teeth.

[0033]

[0029] Another object of the invention is to disclose a strip as defined above, wherein the strip comprises an erosible surface, the surface is characterized by that it comprises both (i) at least one first therapeutic-agent rich portion (TARP); and (ii) at least one second portion having a significantly lower TARP content.

[0034]

[0030] Another object of the invention is to disclose a strip as defined above, wherein the erosible surface further comprises TARP -antitoxic compositions in the at least one second portion of significantly lower TARP content.

[0035]

[0031] Another object of the invention is to disclose a strip as defined above, wherein said erosible surface comprises PVA-CMC-HPMC and said TARP is NaF.

[0036]

[0032] Another object of the invention is to disclose a strip as defined in any of the above, wherein the TARP is a fluoride-containing substance.

[0037]

[0033] Another object of the invention is to disclose a strip as defined in any of the above, wherein the TARP is selected from a group consisting of a whitening agent, a desensitizing agent, remineralization agents, a pH buffer, an antimicrobial agent.

[0038]

[0034] Another object of the invention is to disclose a strip as defined in any of the above, wherein the antimicrobial agent is selected from a group consisting of Aloe Vera, Amoxicillin, Amoxiclav, Azithromycin, Benzalkonium Chloride, Bergamot Oil (Citrus bergamia), Calcium Hydroxide, Cetylpyridinium Chloride (CPC), Chloramphenicol, Chlorhexidine (CHX), Chloroxylenol, Cinnamon Oil (Cinnamomum verum), Ciprofloxacin, Clindamycin, Clotrimazole, Clove Oil (Syzygium aromaticum), Doxycycline, Dicloxacillin, Essential Oils (e.g., eucalyptol, menthol), Fluconazole, Fluoride including Sodium Fluoride, Stannous Fluoride, fluorapatite (Caio(PO4)eF2) and calcium fluoride (CaF?), Hydrogen Peroxide, Iodine- based antiseptics (e.g., Povidone-Iodine), Lactic Acid, Lemon Oil (Citrus limon), Metronidazole, Meropenem, Moxifloxacin, Nystatin, Octenidine Dihydrochloride, Oregano Oil (Origanum vulgare), Peppermint Oil (Mentha piperita), Penicillin, e.g., Penicillin G, Piperacillin-tazobactam, Propolis, Rifampin, Rosemary Oil (Rosmarinus officinalis), Silver Diamine Fluoride, Sodium Hypochlorite, Selenium containing compositions, salts and derivatives thereof, selenious acid selenomethionine selenium-Enriched yeast and extracts thereof, Tetracycline, Tetracyclines (Minocycline, Doxycycline), Tea Tree Oil (Melaleuca altemifolia), Thymus vulgaris, Triclosan (TCS), Ticarcillin-clavulanic acid and any derivatives and combinations thereof.

[0039]

[0035] Another object of the invention is to disclose a strip as defined in any of the above, wherein the antimicrobial agent is selected from a group consisting of Hydrogen Peroxide, Carbamide Peroxide, Sodium Perborate, Sodium Bicarbonate (Baking Soda), Calcium Carbonate, Activated Charcoal, Silica, Fluoride-Containing compositions, Bicarbonate Peroxide, Titanium Dioxide, Tetracycline-Modified Dental Materials, Phthalimidoperoxycaproic Acid (PAP), Kaolin, Blue Covarine, Coconut Oil Pulling Agents, Enzyme-Based Whitening Compounds, including Papain, Bromelain, Lysozyme, Amylase, Lipase, Protease, Urease, Cellulase, Aloe Vera Extract, Papain, and Soursop Extract; antibacterial agents that reduce bacterial adhesion on tooth surfaces, including Chlorhexidine, Cetylpyridinium Chloride (CPC), Sodium Fluoride, Triclosan, Essential Oils (such as thymol, eucalyptol, menthol, and methyl salicylate), Tea Tree Oil, Xylitol, Benzalkonium Chloride, Propylene Glycol, Azithromycin, Metronidazole, Lactoferrin, Propolis, Nisin, Aloe Vera; and any derivatives and combinations thereof.

[0040]

[0036] Another object of the invention is to disclose a strip as defined in any of the above, wherein the desensitizing agent is selected from a group consisting of Potassium Nitrate, Fluoride, Strontium Chloride, Sodium Fluoride, Amorphous Calcium Phosphate (ACP), Calcium Sodium Phosphosilicate (NovaMin), Tricalcium Phosphate (TCP), Dicalcium Phosphate Dihydrate (DCPD), Arginine, Glutaraldehyde, Resin Ionomer Cements, Desensitizing Agents in Varnishes, Trimetaphosphate (TMP), Hexagonal Hydroxyapatite (HAP), Nickel Titanium, Nickel Chloride, Nickel Oxide, Bioglass (45 S5), S53P4 Bioactive Glass, Sol -gel Derived Bioactive Glass and any derivatives and combinations thereof.

[0041]

[0037] Another object of the invention is to disclose a strip as defined in any of the above, wherein the Remineralization Agent is selected from a group consisting of Fluoride, Amorphous Calcium Phosphate (ACP), Calcium Sodium Phosphosilicate (NovaMin), Tricalcium Phosphate (TCP), Dicalcium Phosphate Dihydrate (DCPD), Casein Phosphopeptides (CPP), Nanohydroxyapatite, Xylitol, Recaldent (CPP-ACP), Bioglass, Sodium Bicarbonate (Baking Soda), Sodium Fluoride, Potassium Phosphate, Lactoferrin, Lactate, Green Tea Extract (EGCG), Pectin, Aloe Vera, Collagen Peptides, L-arginine, Seaweed Extracts and any derivatives and combinations thereof.

[0042]

[0038] Another object of the invention is to disclose a strip as defined in any of the above, wherein the strip further comprises a Flavoring and Sensory Enhancement agent, selected from a group consisting of Peppermint Oil, Spearmint Oil, Eucalyptus Oil, Cinnamon Oil, Vanilla Extract, Wintergreen Oil, Clove Oil, Lemon Oil, Strawberry Flavoring, Bubblegum Flavoring, Ginger Root Extract, Honey Flavoring, Apple Flavoring, Peach Flavoring, Orange Flavoring, Grape Flavoring, Mixed Berry Flavoring, Pineapple Flavoring, Watermelon Flavoring, Coconut Flavoring, Anise Oil, Cocoa Flavoring, Sodium Saccharin, Stevia Extract, Citric Acid and any derivatives and combinations thereof.

[0039] Another object of the invention is to disclose a strip as defined in any of the above, wherein the strip further comprises a pH buffer, selected from a group consisting of Sodium Bicarbonate, Sodium Phosphate, Citric Acid and Sodium Citrate, Potassium Phosphate, Calcium Carbonate, Magnesium Hydroxide, Lactic Acid and Lactate Salts, Trometamol (Tris), Arginine, Amino Acids (e.g., Glycine, Histidine), Boric Acid, Sodium Acetate, Acetic Acid and Sodium Acetate, Sodium Citrate, Alpha-Lactalbumin, Sodium Salts of Fatty Acids, Glycyrrhizin, Ascorbic Acid, Sodium Sulfate, Calcium Phosphate, Potassium Bicarbonate, and Phytic Acid.

[0043]

[0040] Another object of the invention is to disclose a strip as defined in any of the above, wherein the strip further comprises a surfactant, selected from a group consisting of anti -Fluorosis Agents (including Sodium Fluoride, Stannous Fluoride, Sodium Monofluorophosphate, Calcium Fluoride, Fluoride Varnishes, Amine Fluoride, Fluoridated Silica), Benzalkonium Chloride, Cocamidopropyl Betaine, Cetylpyridinium Chloride (CPC), Colorants, Decyl Glucoside, Glycerin, Glyceryl Monolaurate, Green Tea Extract, Hydroxyethylcellulose (HEC), Magnesium Aluminum Silicate, Non-Toxic Quaternary Ammonium Compounds (including Benzylalkonium Chloride, Lauralkonium Chloride, Cetyltrimethylammonium Bromide (CTAB)), Polysorbate 20, Polysorbate 80, Quaternary Ammonium Compounds, Sodium Benzoate, Sodium Cocoyl Isethionate, Sodium Dodecyl Sulfate (SDS), Sodium Lauryl Sulfate (SLS), Sodium Saccharin, Sodium Stearoyl Lactylate, Sorbitan Monostearate, Sorbitol, Titanium Dioxide, Xanthan Gum, and Xylitol.

[0044]

[0041] Another object of the invention is to disclose a strip as defined in any of the above, wherein the strip further comprises colorants, selected from a group consisting of Alpha-Carotene, Annatto Extract, Beet Juice Powder, Blue 1 (Brilliant Blue), Broccoli Extract, Carotenes (including Beta-Carotene), Carrot Juice Concentrate, Cabbage Color, Chlorophyll, Chlorophyllin, Chia Seed Extract, Elderberry Extract, Food Additives with Color (including Red 40 (Allura Red), Yellow 5 (Tartrazine), Yellow 6 (Sunset Yellow), and Green 3 (Fast Green)), Fruit and Vegetable Extracts (including Blueberry Extract, Strawberry Extract, Spinach Extract, Kale Extract, Red Cabbage Extract, Pomegranate Extract, Grape Skin Extract, Raspberry Extract, and Sweet Potato Extract), Hibiscus Extract, Leucopene, Matcha Green Tea Extract, Paprika Extract, Red and Yellow Bell Pepper Extract, Spirulina Extract, Titanium Dioxide, and Turmeric.

[0045]

[0042] Another object of the invention is to disclose a strip as defined in any of the above, wherein the strip further comprises a formulation for enhanced drug deliver}' in dental care comprising at least one member of a group consisting of Amphiphilic Block Copolymers including PEG- PLA micelles, wherein the micelles encapsulate hydrophobic drugs such as paclitaxel, exemplified by PEG-Polycaprolactone and PEG-PLA for effective drug solubilization; Ethosomes utilizing phosphatidylcholine and ethanol in their composition; Liposomes formulated to deliver therapeutic agents such as Dexamethasone for inflammation and Amoxicillin as an antibiotic, comprising lipid bilayers made from phosphatidylcholine and cholesterol, particularly employing DSPC and L-a-Phosphatidylethanolamine for daig stability and encapsulation; Microemulsions enhancing the solubility of hydrophobic drugs for oral hygiene applications, containing components like Coconut oil, Tween 80, and distilled water for efficient drug solubilization, along with herbal extracts such as ginger for therapeutic effects; Nanostructured Lipid Carriers (NLCs) for sustained release of therapeutic agents like chlorhexidine with compositions of solid lipids like glyceryl monostearate and liquid lipids, improving bioavailability; Nanoemulsions encapsulating agents such as eugenol, formulated with Cremophor EL and water for effective penetration and delivery of active ingredients; Self- Emulsifying Drug Deliver} / Systems (SEDDS) comprised of lipids such as Castor oil and surfactants including Kolliphor RH40, capable of enhancing the solubility and bioavailability medicaments; Solid Lipid Nanoparticles (SLNs) containing antimicrobial agents such as tea tree oil, utilizing solid lipids like glyceryl monostearate and beeswax for sustained release in the oral cavity; and Transferosomes aimed at improving the permeation of therapeutic agents through biological barriers.

[0046]

[0043] Another object of the invention is to disclose a biocompatible erosible article of manufacture (BAOM) for oral care having a main plane XY with a main longitudinal axis X:X, perpendicular width of length Y and thickness Z, where X>T»Z; the plane XY having a lateral cross-section and a frontal cross-section; wherein the lateral cross-section and frontal crosssection exhibit portions with varying TARP content; at least one portion is enriched with relatively high TARP content, and at least one portion has a much lower TARP content.

[0047]

[0044] Another object of the invention is to disclose a strip as defined in any of the above, wherein the lower TARP content portion further comprises one or more TARP-antitoxic compositions.

[0048]

[0045] Another object of the invention is to disclose a strip as defined in any of the above, wherein the TARP-antitoxic composition is selected from a group consisting of methionine and / or vitamin E in Vaseline™; calcium sucrose phosphate; vitamin C; lycopene; mixtures of calcium, vitamin D3, ascorbic acid and antioxidants, and any derivatives and mixtures thereof.

[0046] Another object of the invention is to disclose a strip as defined in any of the above, wherein the TARP-antitoxic composition is located close to the gums and comprises a much lower TARP content than the TARP.

[0049]

[0047] Another object of the invention is to disclose a strip as defined in any of the above, wherein the TARP is positioned on at least one of the following: the occlusal, gingival, mesial, and lateral side of the teeth.

[0050]

[0048] Another object of the invention is to disclose a strip as defined in any of the above. The strip having at least one surface of heterogeneous content of therapeutic agent as defined above, wherein the at least one surface comprises at least one first TARP and at least one second portion having a much lower content of a therapeutic agent; the TARP exhibits a sustained release profile of the therapeutic agent over an extended duration.

[0051]

[0049] Another obj ect of the invention is to disclose a multilayered strip as defined in any of the above; the strip is characterized by a flexible or semi-rigid substrate comprising, embedded or otherwise provided in connection with a TARP; and a bioadhesive film layer ensuring prolonged contact with tooth surfaces; the TARP is selected from one or more members of a group consisting of: a. sodium fluoride or an equivalent thereof concentration in the range of 0.1 - 10% (w: w); b. whitening agent concentration in the range of 0.1 - 50%; c. a desensitizing agent concentration in the range of 0.1 - 10%; d. a remineralization agent concentration in the range of 0.1 - 10%; e. pH buffer concentration in the range of 0.1 - 60%; and f. an antimicrobial agent concentration in the range of 1 - 50%. g. Fluoride from any source at a concentration of 0.05 - 7%.

[0052]

[0050] Another object of the invention is to disclose a strip as defined in any of the above, wherein the bioadhesive film used for prolonged contact with tooth surfaces, comprises one or more members of a group consisting of Chitosan Films (including Chitosan-based mouthwash films, Chitosan / gelatin composite films, Chitosan / sodium alginate films, Chitosan-based antimicrobial films), Gelatin Films (including Gelatin-based drug delivery films, Gelatin / Chitosan films, Gelatin / alginate films, Gelatin-based mucoadhesive films), Polyvinyl Alcohol (PVA) Films (including PVA-based oral patches, PVA / Chitosan films, PVA / hyaluronic acid films, PVA / PEG films), Sodium Alginate Films (including Sodium alginate dental gels, Sodium alginate / gelatin films, Sodium alginate / Chitosan films, Sodium alginate-based mucoadhesive films), Polylactic Acid (PLA) Films (including PLA-based bioactive films, PLA / Polyethylene glycol (PEG) films, PLA / chitosan films, PLA with natural extracts), Hyaluronic Acid Films (including Hyaluronic acid-containing dental films, Hyaluronic acid / Chitosan films, Hyaluronic acid / gelatin films, Hyaluronic acid-based mucoadhesive films), Carbopol Films (including Carbopol-based topical gels, Carbopol / polyvinyl pyrrolidone (PVP) films, Carbopol / hyaluronic acid films, Carbopol / Chitosan films), Pectin Films (including Pectin-based oral care films, Pectin with Calcium ions films, Pectin / Gelatin films, Pectin-based drug delivery films), Polycaprolactone (PCL) Films (including PCL-based slow-release films, PCL with hydroxyapatite films, PCL / PLGA (Poly(lactic-co-glycolic acid)) films, PCL-based antimicrobial films), Ethyl Cellulose Films (including Ethyl cellulose matrices in drug delivery systems, Ethyl cellulose / PEG films, Ethyl cellulose / chitosan films, Ethyl cellulose / hydroxypropyl methylcellulose (HPMC) films) and any derivatives and mixtures thereof.

[0053]

[0051] Another object of the invention is to disclose a strip as defined in any of the above, wherein it comprises a substrate at least partially constructed from polypropylene carbonate).

[0054]

[0052] Another object of the invention is to disclose a strip as defined in any of the above, wherein it comprises an outer layer that provides structural support and adhesion to the teeth, wherein the outer layer is formed from materials selected from the group consisting of polyethylene (PE) film, polypropylene (PP) film, ethylene vinyl acetate (EVA), and hydrocolloid-based adhesives, wherein the materials possess properties of flexibility and strength.

[0055]

[0053] Another object of the invention is to disclose a strip as defined in any of the above, wherein the adhesive in the outer layer can be applied using methods selected from the group consisting of spray coating and lamination processes, providing versatility in manufacturing.

[0056]

[0054] Another object of the invention is to disclose a strip as defined in any of the above, wherein it comprises a supporting layer that is a soft and foamy structure containing fluoride and remineralization agents, providing cushioning and conformability for improved contact with the teeth, wherein the supporting layer is made from materials selected from the group consisting of polyurethane foam, polyvinyl alcohol (PVA) foam, and hydrophilic polyurethane foam.

[0057]

[0055] Another object of the invention is to disclose a strip as defined in any of the above, wherein the fluoride agents are selected from the group consisting of sodium fluoride, stannous fluoride, and amine fluoride, and wherein the remineralization agents are selected from calcium phosphate in the range of 0.5% to 5%, tri calcium phosphate (TCP) in the range of 0.5% to 5%, hydroxyapatite, xylitol within the range of 10% to 35%, casein phosphopeptides (CPP), calcium citrate, and magnesium phosphate.

[0058]

[0056] Another object of the invention is to disclose a strip as defined in any of the above, wherein it comprises an internal layer that maximizes fluoride delivery and enhances remineralization, wherein the internal layer is made from materials selected from the group consisting of gelatinbased or hydrogel films, chitosan film, and poloxamer gel / film.

[0059]

[0057] Another object of the invention is to disclose a strip as defined in any of the above, wherein the active ingredients in the internal layer are selected from the group consisting of sodium fluoride, calcium phosphate, hydroxyapatite, fluorhydroxyapatite, calcium bicarbonate, and sodium citrate.

[0060]

[0058] Another object of the invention is to disclose a method of manufacturing a dental strip as defined in any of the above, wherein the layers are laminated together using heat or pressuresensitive adhesives, and wherein fluoride and remineralization agents are applied to the foam or film layers through spray coating or dip coating methods.

[0061]

[0059] Another object of the invention is to disclose a method of Die-Cutting of Strips dental strip as defined in any of the above, wherein the assembled strips are die-cut into custom shapes that conform to the contours of both the upper and lower teeth to ensure optimal fit and effectiveness during use.

[0062]

[0060] Another object of the invention is to disclose a method for delivering TARP to teeth, comprising: providing a dental strip as defined in any of the above, comprising a flexible substrate; providing the substrate to contain TARP in an effective amount by weight; and applying the strip to the teeth in a way the TARP is positioned away from the gum, for a treatment period of at least 10 seconds.

[0063]

[0061] Another obj ect of the invention is to disclose a strip as defined in any of the above, additionally comprising at least one auxiliary from a group consisting of fixating and immobilizing means, manipulating and administering means, color marks, barcodes, and QR codes, X-ray readable markers and any other marker in use in oral care; sensors and indicators, including pH- indicators, time-of-use indicators, expiration-date indicators, sugar-indicators, medicamentindicators, inflammatory- and microbial-indicators, communication means, RFID and any combination thereof.

[0062] Another object of the invention is to disclose a dental strip kit comprising a dental strip as defined in any of the above, comprising multiple layers for delivering at least one TARP to teeth and gums, characterized by a lower layer providing structural support and adhesive properties for secure adhesion to teeth; a middle layer that is foamy and soft, facilitating penetration into dental cavities and micro-grooves while carrying fluoride and calcium phosphate to strengthen enamel; and an upper layer containing active therapeutics, further comprising at least two members of a group consisting of sodium fluoride and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) for remineralization and decay protection; clear and detailed Instructions for Use (IFU) outlining preparation, placement, recommended duration, post-use guidelines, precautions, warnings, and storage instructions; a specialized application tool for hygienic and accurate application of the dental strip; a durable storage case designed to prevent exposure to moisture, light, and contamination while organizing additional components; an adhesive or retention component to enhance the adherence of the dental strip to teeth; a user-friendly timer for monitoring application duration; a post-treatment product for enhancing the effectiveness of the strip and soothing the oral cavity; a pre-use care product for cleansing teeth of debris to optimize adhesion; and comprehensive safety information detailing potential side effects, contraindications, warnings, and risks to, a plurality of embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

[0064] BRIEF DESCRIPTION OF THE DRAWINGS

[0065]

[0063] In order to better understand the invention and its implementation in practice, a plurality of embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:

[0066]

[0064] FIG. 1 graphically illustrates dental anatomy, terminology, and measures;

[0067]

[0065] FIG. 2a, b schematically illustrates various arrangements of dental strips according to a preferred embodiment of the present invention;

[0068]

[0066] FIG. 3 schematically illustrates various arrangements of dental strips according to a preferred embodiment of the present invention;

[0069]

[0067] FIG. 4 schematically illustrates various arrangements of dental strips according to a preferred embodiment of the present invention;

[0070]

[0068] FIG. 5 schematically illustrates a dental strip according to a preferred embodiment of the present invention; and

[0069] Fig. 6 illustrates the cumulative release of NaF over time from thin, medium thickness, and thick film samples, demonstrating that the release of NaF does exhibit a non-diffusion-based pattern according to a preferred embodiment of the present invention.

[0071] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0072]

[0070] The following description is provided so as to enable any person skilled in the art to make use of the invention and sets forth the best modes contemplated by the inventor of carrying out this invention. Various modifications, however, are adapted to remain apparent to those skilled in the art, since the generic principles of the present invention have been defined specifically to provide a chiral or non-homogeneous spread of a therapeutic agent on the surface of a dental strip.

[0073] Benefits of High-Fluoride Dental Strips for Home Care

[0074]

[0071] The introduction of high-fluoride concentration dental strips designed for at-home use offers numerous advantages that enhance oral health, particularly in the prevention and management of dental caries. These benefits address the challenges associated with traditional treatments, such as fluoride varnishes typically applied in dental clinics.

[0075]

[0072] Targeted Delivery and Enhanced Bioavailability: High-fluoride dental strips provide targeted delivery of fluoride ions directly to tooth surfaces. This localized method increases the bioavailability of fluoride, ensuring optimal concentrations at the site of application. Studies show that topical applications of fluoride can significantly elevate fluoride levels in saliva and dental plaque, promoting the formation of fluorapatite, a more acid-resistant derivative of hydroxyapatite that strengthens enamel and increases its resilience against demineralization.

[0076]

[0073] Sustained Fluoride Release: Maintaining low but effective fluoride concentrations (e.g., 0.01% to 0.1%) over an extended duration is crucial for effective caries prevention. Traditional fluoride treatments often result in brief retention times, necessitating frequent applications to maintain their efficacy. In contrast, high-fluoride dental strips can deliver a continuous and sustained release of fluoride, effectively reducing the risk of dental fluorosis-a condition linked to excessive fluoride exposure-while still providing protective benefits.

[0077]

[0074] Effective Reduction in Caries Incidence: High concentrations of fluoride, such as those used in professional treatments, have proven to significantly decrease the incidence of dental caries, especially in high-risk populations. By integrating these active materials into dental strips, individuals can engage in consistent fluoride treatments at home, which is particularly beneficial for children who may not have regular access to professional dental care.

[0075] User-Friendly and Compliant Application: Dental strips offer an easy-to-use and comfortable alternative to traditional fluoride varnishes that require professional application. Fluoride varnishes, usually containing around 5% fluoride, are applied by dentists and may not be practical for daily at-home use. By utilizing fluoride strips, patients-especially children-are more likely to comply with fluoride treatment regimens, as parents can easily administer the strips at home, ensuring consistent fluoride exposure.

[0078]

[0076] Cost Savings and Efficient Use of Dental Resources: Moving to high-fluoride dental strips for at-home use can result in significant cost savings. By reducing the frequency of office visits for fluoride varnish applications, dental practices can free up valuable chair time for other essential treatments, thus optimizing resource allocation. This efficiency means that patients can receive effective fluoride treatment without the associated costs and time commitment of regular dental appointments.

[0079]

[0077] Minimized Risk of Excessive Fluoride Exposure: High-fluoride dental strips provide controlled dosing of fluoride, as each strip is engineered to deliver a specific amount. This precise formulation minimizes the risk of accidental overdose from other sources of fluoride, such as toothpaste or drinking water. This method aligns with recommendations from regulatory bodies regarding safe fluoride intake, helping to prevent dental fluorosis.

[0080]

[0078] Enhanced Remineralization and Antibacterial Effects: High levels of fluoride in dental strips promote remineralization of early carious lesions and reinforce enamel structure effectively. Research has indicated that fluoride strips made from polypropylene carbonate) (PPC) show outstanding remineralization and antibacterial properties when concentrations reach up to 5%. In vitro studies further reveal consistent fluoride release over a prolonged period-approximately 100% over 24 days-without any initial burst, ensuring long-term protection with minimal side effects.

[0081]

[0079] Avoiding Unpleasant Treatment Experiences: Traditional fluoride varnish applications often involve procedures that some patients find uncomfortable or unpleasant, including the use of arch trays that may not fit well and the necessity for isolated treatment areas. High-fluoride dental strips offer a more pleasant patient experience as they eliminate the need for such invasive procedures, allowing individuals to apply treatment conveniently in a non-clinical environment.

[0082]

[0080] Bridging Oral Health Disparities: Dental caries impact certain groups disproportionately, particularly low-income and minority populations. Fluoride-infused dental strips provide an accessible and effective solution that empowers individuals and addresses systemic health inequities. These strips facilitate uniform preventive care across various demographics, thereby enhancing overall public health.

[0083]

[0081] Supporting Integrated Oral Health Approaches: The design of fluoride dental strips allows for further innovation, including the possible addition of other preventive agents such as antibacterial compounds. This comprehensive approach offers robust oral care solutions while reducing risks associated with traditional fluoride varnish applications that require professional oversight and can expose patients to high fluoride concentrations.

[0084]

[0082] In conclusion, high-fluoride dental strips for at-home care present a significant advancement in preventive dental technology. They not only provide effective caries prevention but also enhance accessibility, compliance, and safety while addressing many of the limitations found in current fluoride treatments applied in clinical settings. By empowering patients to take control of their oral health, high-fluoride dental strips have the potential to transform everyday oral care practices while minimizing costs and improving patient experiences.

[0085]

[0083] It is thus provided in a non-limiting manner, by one embodiment of the invention, a dental strip comprising a flexible substrate constructed from a polymeric material, specifically polypropylene carbonate (PPC). This material exhibits excellent mechanical properties, including a tensile strength (TS) ranging from about 20 to about 40 MPa, which indicates robust structural integrity suitable for oral applications. Furthermore, the elongation at break (EB) of the NaF-PPC strips is enhanced with increased drug loading, demonstrating adaptability under typical flexural forces encountered in the oral environment.

[0086]

[0084] The strip of material may further comprise materials such as polymers, natural and synthetic wovens, non-wovens, foil, paper, rubber, and combinations thereof. The strip of material may be a single layer of material or a laminate of more than one layer. Generally, the strip of material is substantially water impermeable. The material may be any type of polymer that meets the required flexural rigidity and is compatible with tooth whitening actives, such as peroxide. The material may comprise a single polymer or a mixture of polymers. Suitable polymers include, but are not limited to, polyethylene, ethylvinylacetate, ethylvinyl alcohol, polyesters such as Mylar® manufactured by DuPont, fluoroplastics such as Teflon® manufactured by DuPont, and combinations thereof. The material may be polyethylene. The strip of material is generally less than about 1 mm thick, or less than about 0.05 mm thick, or from about 0.001 to about 0.03 mm thick. A polyethylene strip of material may be less than about 0.1 mm thick or from about 0.005 to about 0.02 mm thick.

[0087]

[0085] The term "strip" as used herein comprises a material whose longest dimension length is generally greater than its width, and whose width is generally greater than its thickness. Strips may be rectangular, arched, curved, semi-circular, and have rounded comers to avoid irritation of the soft tissue of the oral cavity. "Rounded corners" or "rounded shapes" as used herein means generally lacking sharp angles or points, for example one or more angles of 135° or less. In addition, a strip may be bent or shaped into three dimensional shapes, for example into a dental arch, or combinations thereof. Strips may be solid, textured, rigid, moldable, deformable, permanently deformable, or combinations thereof. Strips useful in the present invention may be suitably shaped to fit into an oral cavity.

[0088] Fluoride-Releasing Agent

[0089]

[0086] It is another embodiment of the invention to incorporate a fluoride-releasing agent embedded within the flexible substrate to provide a controlled release of fluoride ions. In this embodiment, the fluoride concentration can vary, with formulations containing sodium fluoride (NaF) at concentrations ranging from 1.25% to 5% by weight. When the fluoride content increases, the drug loading efficiency (DL%) increases from 0.72% to 2.65%. Importantly, the encapsulation efficiency (EE%) remains above 50%, highlighting the efficacy of the manufacturing process and the substrate's capability to retain fluoride.

[0090] Fluoride Release Profile

[0091]

[0087] It is an additional embodiment of the invention to illustrate that the fluoride release profile from the NaF-PPC strips demonstrates a sustained release mechanism over an extended duration of 24 days. The cumulative release data indicates that fluoride is released through a two-step profile, initially showing a linear release for the first 24 days and subsequently declining to a plateau, wherein therapeutic fluoride levels are maintained. Notably, strips with higher fluoride concentrations (e.g., 5%) exhibit accelerated release rates compared to those with lower concentrations, providing effective management of fluoride levels in the oral cavity over prolonged periods.

[0092] Enhanced Anticaries Effects

[0093]

[0088] It is a further embodiment of the invention to posit that the sustained low-level presence of fluoride in saliva from these strips significantly contributes to anticaries effects. This is based on the established correlation between fluoride concentrations in oral fluids and the incidence of dental caries. By maintaining fluoride above critical thresholds, these strips serve not only as therapeutic agents but also as preventive measures against tooth decay and acidity buffering. Layer Integration for Enhanced Efficacy

[0094]

[0089] It is another embodiment of the invention to emphasize that the dental strip incorporates various specific layers designed to enhance performance:

[0090] Hydrogel -Based Layer: This layer utilizes a hydrophilic matrix that allows for optimal moisture retention and facilitates the encapsulation of active ingredients, such as sodium fluoride, potassium nitrate, selenium, triclosan and xylitol, improving contact time with tooth surfaces.

[0095]

[0091] Bioadhesive Film Layer: A bioadhesive film layer is designed to ensure prolonged adherence to dental surfaces, maximizing the delivery of active ingredients by maintaining contact with the enamel for optimal fluoride absorption.

[0096]

[0092] Silicone-Based Layer: This soft silicone layer improves patient comfort and minimizes irritation to the gums, enhancing user experience during treatment.

[0097]

[0093] Electrospun Nanofiber Layer: This innovative approach incorporates nanofibers to create a large surface area for active ingredient delivery, allowing for controlled release and targeted treatments, particularly effective for localized dental issues, such as sensitivity or early decay. Antimicrobial Properties

[0098]

[0094] It is a further embodiment of the invention to highlight that the fluoride-containing dental strips exhibit enhanced antimicrobial properties, particularly at elevated fluoride concentrations. The antibacterial efficacy of these strips, evaluated through the plate counting method, demonstrates a reduction in bacterial colony counts by over 90% for strips with 2.5% and 5% fluoride content, which significantly contributes to improved oral health and the prevention of secondary caries associated with bacterial adhesion. It is a further embodiment of the invention wherein various antimicrobial agents are used or co-used, such as those selected from a group consisting of Aloe Vera, Amoxicillin, Amoxiclav, Azithromycin, Benzalkonium Chloride, Bergamot Oil (Citrus bergamia), Calcium Hydroxide, Cetylpyridinium Chloride (CPC), Chloramphenicol, Chlorhexidine (CHX), Chloroxylenol, Cinnamon Oil (Cinnamomum verum), Ciprofloxacin, Clindamycin, Clotrimazole, Clove Oil (Syzygium aromaticum), Doxycycline, Dicloxacillin, Essential Oils (e.g., eucalyptol, menthol), Fluconazole, Fluoride (e.g., Sodium Fluoride, Stannous Fluoride), Hydrogen Peroxide, Iodine-based antiseptics (e.g., Povidone-Iodine), Lactic Acid, Lemon Oil (Citrus limon), Metronidazole, Meropenem, Moxifloxacin, Nystatin, Octenidine Dihydrochloride, Oregano Oil (Origanum vulgare), Peppermint Oil (Mentha piperita), Penicillin, e.g., Penicillin G, Piperacillin-tazobactam, Propolis, Rifampin, Rosemary Oil (Rosmarinus officinalis), Silver Diamine Fluoride, Sodium Hypochlorite, Tetracycline, Tetracyclines (Minocycline, Doxycycline), Tea Tree Oil (Melaleuca altemifolia), Thymus vulgaris, Triclosan (TCS), Ticarcillin-clavulanic acid.

[0099] Integration with Teeth Whitening Systems

[0100]

[0095] It is yet another embodiment of the invention to integrate the dental strip within a multi -phase oral composition for whitening teeth. This embodiment includes:

[0096] Delivery Carrier Options: Various delivery carriers selected from strips, dental trays, and sponge materials to facilitate user-friendly application.

[0101]

[0097] Bleaching Agent Composition: A dual-phase composition comprising a discontinuous aqueous phase with a bleaching agent in varying concentrations, from 0.002% to 10% by weight, with the predominant hydrophobic phase making up at least 50% of the formulation. This composition can utilize agents like peroxides or hydroxyapatite as described in EP1438928B1 and US5639445A.

[0102]

[0098] Electromagnetic Radiation Source: An electromagnetic radiation source capable of emitting wavelengths from 200 nm to 1700 nm, working synergistically with the whitening composition to enhance bleaching efficacy.

[0103] Dental Treatment Devices and Kits

[0104]

[0099] It is another embodiment of the invention to disclose kits containing:

[0105]

[0100] Dental Trays: Non-customized dental trays formed with moisture-resistant barrier layers adaptable to various dental arches, mirroring designs in US7452209B2 and EP1779846A2.

[0106]

[0101] Dental Treatment Compositions: Combining whitening and desensitizing agents, each with increased adhesiveness when moistened, contained within a tray-like configuration for convenience and ease of use. Kits could also incorporate heating elements to optimize treatment composition activation as described in AU2001259622A1.

[0107]

[0102] Electrochemical Devices: Methods that utilize electrodes to apply electric current for enhanced absorption of active agents, facilitating the treatment of dental conditions.

[0108] Methods of Application

[0109]

[0103] It is a further embodiment of the invention to describe the methods of applying the dental strips to ensure effective treatment. The application steps generally consist of:

[0110]

[0104] Preparing the Dental Surface: Cleaning the tooth surface to ensure optimal exposure of enamel.

[0111]

[0105] Applying the Strip: The dental strip is positioned directly onto the tooth surface where the released agent from the substrate provides therapeutic benefits over a specified duration, allowing for effective treatment outcomes.

[0112] Flavoring and Sensory Enhancement

[0113] It is an additional embodiment of the invention to include flavoring agents or sensory enhancers within the dental strips. These additives can improve patient compliance by masking the taste of fluoride or providing a pleasant flavor, thus making regular use more enjoyable. Such Flavoring and Sensory Enhancement are selected in a non-limiting manner from a group consisting of Peppermint Oil, Spearmint Oil, Eucalyptus Oil, Cinnamon Oil, Vanilla Extract, Wintergreen Oil, Clove Oil, Lemon Oil, Strawberry Flavoring, Bubblegum Flavoring, Ginger Root Extract, Honey Flavoring, Apple Flavoring, Peach Flavoring, Orange Flavoring, Grape Flavoring, Mixed Berry Flavoring, Pineapple Flavoring, Watermelon Flavoring, Coconut Flavoring, Anise Oil, Cocoa Flavoring, Sodium Saccharin, Stevia Extract, Citric Acid.

[0114] Customization Options

[0115]

[0106] It is another embodiment of the invention to allow for customization of the dental strips based on individual patient needs. This may include varying the concentration of fluoride or incorporating additional active ingredients such as xylitol or calcium phosphates for added benefits.

[0116] Multi-Functional Strips

[0117]

[0107] It is yet another embodiment of the invention to create multi-functional dental strips that combine the benefits of fluoride release, remineralization, teeth whitening, and desensitization in a single product. This would involve layering technologies to incorporate multiple active agents, catering to a wider range of dental issues in one application.

[0118] Advanced Composition for Enhanced Effectiveness

[0119]

[0108] It is an additional embodiment to explore advanced formulations where the dental strip includes composite layers that contain both whitening agents such as hydroxyapatite and fluoride, improving both aesthetic results and dental health as seen in US20150238292A1.

[0120] Ion Exchange Capabilities

[0121]

[0109] It is another embodiment of the invention to incorporate an ion exchange mechanism within the dental strip, allowing for enhanced active agent delivery through ionic exchange processes, providing additional therapeutic benefits as described in EP3257467B1.

[0122] Elasticity and Flexibility Considerations

[0123]

[0110] It is yet another embodiment to ensure that the dental strip maintains optimum elasticity, allowing it to conform closely to the unique structure of each patient's dental arch. This elasticity is essential for maximizing contact with tooth surfaces to allow for efficient treatment delivery as seen in some of the published patents.

[0124]

[0111] It is according to another embodiment of the invention to utilize dental strips designed for home use, comprising a flexible substrate constructed from a polymeric material, specifically polypropylene carbonate) (PPC). This material is selected for its excellent mechanical properties, biocompatibility, and ability to provide sustained fluoride release, thereby enhancing the effectiveness of fluoride applications for caries prevention.

[0125]

[0112] In one embodiment, the dental strips contain a fluoride content ranging from 1.25% to 7% by weight. This ensures that an effective concentration of fluoride is delivered directly to the tooth surfaces during home treatment. The fluoride is incorporated in the form of sodium fluoride (NaF), which is uniformly distributed within the substrate to provide a controlled release mechanism, allowing for prolonged exposure to fluoride. In one embodiment, the dental strips contain bendable plastic strips: strips with improved adhesion.

[0126] Safety and Standards of Use

[0127]

[0113]

[0113] ISO 17730:2020 72166 Dentistry -Fluoride varnishes Requirements and test methods for total digestible fluoride content and a minimum soluble fluoride release potential in dental varnishes containing fluoride, intended for use in the oral cavity directly on the outer surfaces of teeth and fillings. It also specifies packaging and labeling requirements, including the instructions for use. This document covers fluoride varnishes to be applied by dental healthcare workers.

[0128]

[0114] According to another embodiment of the invention, the dental strips are formulated such that they achieve a minimum soluble fluoride release potential that complies with the specifications set forth in ISO 17730:2020 72166. This ensures that the strips deliver fluoride ions effectively and consistently over time, contributing to the remineralization of enamel and the reduction of dental caries.

[0129]

[0115] In a preferred embodiment, the dental strips may also include additional active agents. These may be selected from antibacterial compounds, remineralizing agents, and flavoring agents, which work synergistically with fluoride to enhance oral health benefits and improve the consumer experience during application.

[0130]

[0116] It is also an embodiment of the invention that the packaging for these dental strips is designed to be moisture-resistant, ensuring the integrity of the fluoride formulation is maintained prior to use. Each package includes clear labeling and detailed instructions that comply with the requirements of ISO 17730:2020 72166, providing guidance to users on safe and effective application methods.

[0131]

[0117] Furthermore, it is according to an embodiment of the invention that the dental strip retains physical flexibility and sufficient adhesive properties, allowing it to conform closely to the contours of the tooth surfaces during application. This feature significantly enhances the effectiveness of fluoride delivery, ensuring that the therapeutic benefits are maximized. To promote hygiene and prevent contamination, each dental strip is designed for single use. This aligns with the overall safety profile of the product and ensures optimally efficacy in fluoride treatment

[0132]

[0118] Reference is now made to figure 1, schematically illustrating dental anatomy, and shows teeth numbering, typical dimensions, teeth types etc. Crown portion (101) with uppermost portion 105 facing the chewing surface, and a lower portion 106, located adjacent the gums (107b); Root portion of the tooth (101-102) is located below gums upper surface 107a. The terms used herein are as follows: Distal - The surface that is away from the midline of the face. Facial - The surface that faces the cheeks or lips. The following terms are also in use herein: Labial - The surface towards the lips; Buccal - The surface towards the cheeks; Incisal - The biting edge of an anterior tooth; Lingual - The surface that faces the tongue; Mesial - The surface that is closest to the midline of the face; Occlusal- The chewing surface of posterior teeth; and Proximal - Tooth surfaces that are next to each other (e.g., distal of lateral incisor and mesial of canine). Hence, lingual and buccal surfaces, 103-104 are shown.

[0133]

[0119] Reference is now made to figures 2a-2b, schematically illustrating strips according a few embodiments of the invention. Both strips of Fig. 2a and Fig. 2b comprise two main surfaces (sides): one is facing either the buccal or lingual sides and saliva thereof, namely surface 100a, and the opposite one is facing the teeth and immobilized (anchored, glued or otherwise affix) to at least one tooth 100b (see Fig. 3). It is thus well in the scope of the invention wherein the fluoride content on surface 100a is heterogenous, namely surface 100a comprises at least one first portion which is enriched with relatively high fluoride content, and at least one second portion with comprises much lower fluoride content.

[0134]

[0120] Fig. 2a shows an out-of-scale perspective view of surface 100a in a strip having an elongated leaflet-like shape. The strip is characterized by width 201, length 202, and thickness. Therapeutic-agent rich portion (TARP) selected from either or both at least one fluoride-rich portion and at least one portion rich with other therapeutic-agents for dental care 203 of the strip is configured to affix the teeth and release fluoride. Fluoride-free portion, or otherwise, a portion with lower fluoride content 204 (both are denoted here as 'fluoride free portion") is facing the gums. Indication 205 clearly shows the patient where is the TARP and where is the fluoride-free portion. Indication 205 is selected from a group consisting of printed line, printed area, indicia such as marks, characters, text, arrows, of icons, texture, shape and a combination of the same. Optionally, surface 100a may comprise at least one third portion 206, which is another fluoride free portion, and located away from the gums.

[0135]

[0121] Increased exposure to fluorine-containing compounds leads to accumulation of fluorides in hard tissues of bones and teeth, which may result in numerous skeletal and dental disorders, such as fluorosis, i.e., pathological changes in the structure and function of bones and teeth. Fig. 2b similarly shows an out-of-scale perspective view of surface 100a in another type of strip according to yet another embodiment of the invention. The strip comprises at least one first TARP 211, neighboring at least one second TARP 210. The one or more TARPs 210 comprises fluoride-antitoxic compositions, such as methionine and / or vitamin E in Vaseline™; calcium sucrose phosphate; vitamin C; lycopene; mixtures of calcium, vitamin D3, ascorbic acid and antioxidants, and any derivatives and mixtures thereof.

[0136]

[0122] Hence, strips of Fig. 2a-2b discloses means for oral care, whereat fluoride content on their surface 100a is heterogenous, namely surface 100a comprises at least one first TARP which is enriched with relatively high fluoride content, and at least one second portion with comprises much lower fluoride content [and / or fluoride-antitoxic compositions],

[0137]

[0123] Reference is now made to figures 3, schematically illustrating lateral cross sections (301a, 301b) and multiple frontal cross-sections (depicted from front side, namely via side 302) of strips according a few embodiments the invention.

[0138]

[0124] Dental strip 301a has a non-square rectangular and / or somewhat rounded shape, where side 302 is intended to be affixed adjacent the gums, and side 303 is configured to be set opposite the gums. Strip 301a is structured as a multilayer, including, e.g., semiflexible adhesive 304 to be reversibly attached with at least one tooth; basal (structural-) layer 305a, at least one first fluoride high-content accommodating layer 306a and at least one second fluoride releasing layer 307. The layers may be constructed in parallel or not. Dental strip 301b, for example, has an arc-like structure 305b and a complex shaped fluoride high-content accommodating layer 306b, having more fluoride content on edges, namely at sides 302 and 303 and less fluoride content at the center. Scheme 340 presents front cross section (via 302) of the same, still in an out-of-scale manner.

[0139]

[0125] Reference is made again to any of figures 2a, 2b and 3, schematically depicting a set of multilayered strips according to some embodiments of the invention. The strips are characterized by at least one flexible or semi-rigid substrate that comprises, embedded or otherwise provided in connection with one or more TARPs. The strip also comprises at least one bioadhesive film or layer ensuring prolonged contact with tooth surfaces. The therapeutic agent(s) is / are selected from one or more members of a group consisting of: a. sodium fluoride or an equivalent thereof concentration in the range of 0.1 - 10% (w:w); b. whitening agent concentration in the range of 0.1 - 50%; c. a desensitizing agent concentration in the range of 0.1 - 10%; d. a remineralization agent concentration in the range of 0.1 - 10%; e. pH buffer concentration in the range of 0.1 - 60%; and f. an antimicrobial agent concentration in the range of 1 - 50%. g. Fluoride from any source at a concentration of 0.05 - 7%.

[0126] Both strips of Fig. 2a and Fig. 2b comprise two main surfaces (sides): one is facing either the buccal or lingual sides and saliva thereof, namely surface 100a, and the opposite one is facing the teeth and immobilized (anchored, glued or otherwise affix) to at least one tooth 100b (see Fig. 3). It is thus well in the scope of the invention wherein the content of the therapeutic agent on surface 100a is heterogenous, namely surface 100a comprises at least one first portion which is enriched with relatively high therapeutic agent content, and at least one second portion with comprises much lower therapeutic agent content.

[0140]

[0127] Fig. 2a shows an out-of-scale perspective view of surface 100a in a strip having an elongated leaflet-like shape. The strip is characterized by width 201, length 202, and thickness. Therapeutic-agent rich portion (TARP) selected from either or both at least one therapeutic agent -rich portion and at least one portion rich with other therapeutic-agents for dental care 203 of the strip is configured to affix the teeth and release therapeutic agent, therapeutic agent -free portion, or otherwise, a portion with lower fluoride content 204 (both are denoted here as "therapeutic agent free portion") is facing the gums. Indication 205 clearly shows the patient where is the TARP and where is the therapeutic agent -free portion. Indication 205 is selected from a group consisting of printed line, printed area, indicia such as marks, characters, text, arrows, of icons, texture, shape and a combination of the same. Optionally, surface 100a may comprise at least one third portion 206, which is another fluoride free portion, and located away from the gums.

[0141]

[0128] Increased exposure to therapeutic agent leads to accumulation of fluorides in hard tissues of bones and teeth, which may result in numerous skeletal and dental disorders. Fig. 2b similarly shows an out-of-scale perspective view of surface 100a in another type of strip according to yet another embodiment of the invention. The strip comprises at least one first TARP 211, neighboring at least one second TARP 210. The one or more TARPs 210 comprises therapeutic agent-antitoxic compositions, such as methionine and / or vitamin E in Vaseline™; calcium sucrose phosphate; vitamin C; lycopene; mixtures of calcium, vitamin D3, ascorbic acid and antioxidants, and any derivatives and mixtures thereof.

[0142]

[0129] Hence, strips of Fig. 2a-2b discloses means for oral care, whereas therapeutic agent content on their surface 100a is heterogenous, namely surface 100a comprises at least one first TARP which is enriched with relatively high content of therapeutic agent, and at least one second portion with comprises much lower content of therapeutic agent [and / or therapeutic agent- antitoxic compositions].

[0130] Reference is now made again to figures 3, schematically illustrating lateral cross sections (301a, 301b) and multiple frontal cross-sections (depicted from front side, namely via side 302) of strips according a few embodiments the invention.

[0143]

[0131] Dental strip 301a has a non-square rectangular and / or somewhat rounded shape, where side 302 is intended to be affixed adjacent the gums, and side 303 is configured to be set opposite the gums. Strip 301a is structured as a multilayer, including, e.g., semiflexible adhesive 304 to be reversibly attached with at least one tooth; basal (structural-) layer 305a, at least one first therapeutic agent high-content accommodating layer 306a and at least one second therapeutic agent releasing layer 307. The layers may be constructed in parallel or not. Dental strip 301b, for example, has an arc-like structure 305b and a complex shaped therapeutic agent high- content accommodating layer 306b, having more content of the therapeutic agent on edges, namely at sides 302 and 303 and less content therapeutic agent at the center. Scheme 340 presents front cross section (via 302) of the same, still in an out-of-scale manner.

[0144]

[0132] The term "surfactants" refers in a non-limiting manner to Anti-Fluorosis Agents (including Sodium Fluoride, Stannous Fluoride, Sodium Monofluorophosphate, Calcium Fluoride, Fluoride Varnishes, Amine Fluoride, Fluoridated Silica), Benzalkonium Chloride, Cocamidopropyl Betaine, Cetylpyridinium Chloride (CPC), Colorants, Decyl Glucoside, Glycerin, Glyceryl Monolaurate, Green Tea Extract, Hydroxyethylcellulose (HEC), Magnesium Aluminum Silicate, Non-Toxic Quaternary Ammonium Compounds (including Benzylalkonium Chloride, Lauralkonium Chloride, Cetyltrimethylammonium Bromide (CTAB)), Polysorbate 20, Polysorbate 80, Quaternary Ammonium Compounds, Sodium Benzoate, Sodium Cocoyl Isethionate, Sodium Dodecyl Sulfate (SDS), Sodium Lauryl Sulfate (SLS), Sodium Saccharin, Sodium Stearoyl Lactylate, Sorbitan Monostearate, Sorbitol, Titanium Dioxide, Xanthan Gum, and Xylitol.

[0145]

[0133] The term also refers to list of oil-in-water (O / W) or water-in-oil (W / O) vesicles, liposomes, and ethosomes useful in dental care such as Amphiphilic Block Copolymers (including PEG- PLA micelles for delivery of hydrophobic drugs like paclitaxel), (Examples: PEG- Polycaprolactone: Polymers that form micelles for delivery, PEG-PLA: Polyethylene glycol (PEG) combined with poly(lactic acid) (PLA) for encapsulation of drugs), Ethosomes (including Entacapone ethosomes for antiparkinsonian therapy, Ropivacaine ethosomes for local anesthesia, Curcumin ethosomes for anti-inflammatory effects), (Examples: Phosphatidylcholine and ethanol for enhanced permeability, Sodium cholate and Tween 80 mixed with lipid components), Liposomes (including Dexamethasone liposomes for inflammation, Curcumin liposomes for antioxidant therapy, Amoxicillin liposomes for antibiotic delivery, Fluorinated liposomes for tracking and drug delivery of fluorophores), (Examples: Lipid bilayers made of phosphatidylcholine and cholesterol (e.g., DSPC (1,2- Distearoyl-sn-glycero-3-phosphocholine)), DSG (Dipalmitoylphosphatidylcholine) and L-a- Phosphatidylethanolamine for stability and drug encapsulation), Microemulsions (including Coconut oil microemulsion for enhanced solubility in oral hygiene products, Herbal microemulsions with ginger extract for anti-nausea, Mouthwash microemulsions with chlorhexidine for antibacterial purposes), (Examples: Coconut oil, Tween 80, and distilled water for hydrophobic drug solubilization, Isopropyl myristate, surfactants like Polysorbate 20, and water for enhanced stability), Nanostructured Lipid Carriers (NLCs) (including NLCs containing chlorhexidine for prolonged antibacterial effect, Eugenol NLCs for effective pain relief, NLCs for quercetin delivery targeting inflammation), (Examples: Solid lipids like glyceryl monostearate combined with liquid lipids like oleic acid, Beeswax and medium-chain triglycerides for improving bioavailability), Nanoemulsions (including Nanoemulsions with eugenol for analgesic properties, Cinnamon oil nanoemulsion for antifungal effects, Clove oil nanoemulsions for dental pain relief), (Examples: Eugenol, Cremophor EL, and water for effective drug delivery, Cinnamon oil, ethanol, and Hydroxylated lecithin for improved penetration), Self-Emulsifying Drug Delivery Systems (SEDDS) (including SEDDS containing ibuprofen for enhanced pain management, SEDDS with mel oxicam for inflammation reduction, Mouthwash SEDDS incorporating chlorhexidine for targeted antimicrobial action), (Examples: Castor oil, Kolliphor RH40, and ethanol for self-emulsifying properties, Caprylic / capric triglycerides and Glycerol monooleate for improved solubility), Solid Lipid Nanoparticles (SLNs) (including SLNs with tea tree oil for antimicrobial action, SLNs containing fluoride for cavity prevention, Natural SLNs loaded with xylitol for caries prevention), (Examples: Glyceryl monostearate and lecithin for structural integrity, Beeswax and coconut oil for sustained release and biocompatibility), Transferosomes (including Transferosomes with lidocaine for local analgesia, Transferosomes for NTHEs like ibuprofen for pain relief, Curcumin transferosomes for enhanced absorption and anti-inflammatory effects), (Examples: Phosphatidylcholine, ethanol, and sorbitan monostearate for flexible vesicle structure, Cholesterol and Tween 80 for improving drug permeation).

[0146]

[0134] As indicated above, liposomes are versatile nanocarriers that can be tailored for a variety of dental strips as embodied in the invention, offering inter alia enhanced drug delivery, mucoadhesion, targeted and controlled release, and reduced side effects. In conventional liposome-loaded dental strips, typical compositions include phosphatidylcholine (PC) and cholesterol (CHOL) in a 70:30 molar ratio, encapsulating agents such as nisin, chlorhexidine, or cetylpyridinium chloride for antimicrobial effects. Soya lecithin and cholesterol in an 80:20 mass ratio can also be used, loaded with essential oils like thymol or eucalyptol.

[0147]

[0135] For polymer-coated liposome dental strips, liposomes can be coated with mucoadhesive polymers such as chitosan or alginate. For example, a PC / CHOL (60:40) core with a chitosan (0.1% w / v) coating can encapsulate doxycycline or minocycline for periodontal therapy. Alternatively, soya lecithin / CHOL (70:30) liposomes coated with alginate (0.2% w / v) can be loaded with fluoride or calcium phosphate for remineralization.

[0148]

[0136] PEGylated liposome dental strips use polyethylene glycol (PEG) to increase stability and prolong oral retention. Compositions such as PEG-DSPE / PC / CHOL (55:40:5 molar ratio) can encapsulate lidocaine or benzocaine for pain relief, while HSPC / CHOL / mPEG-DSPE (63 :32:5 molar ratio) liposomes can deliver triamcinolone acetonide for oral lichen planus.

[0149]

[0137] Stimuli-responsive liposome dental strips are designed to release their payload in response to environmental triggers. pH-sensitive liposomes composed of DOPE and cholesteryl hemisuccinate (CHEMS) in a 70:30 ratio can encapsulate amoxicillin or metronidazole, releasing the drug in acidic carious lesions. Redox-sensitive liposomes, such as PC / CHOL / PEG-SS-DSPE, can be loaded with antimicrobial peptides for release in inflamed, oxidative environments.

[0150]

[0138] Targeted liposome dental strips employ specific ligands for selective delivery. Folate- conjugated liposomes (PC / CHOL / DSPE-PEG-Folate 65:30:5) can encapsulate doxorubicin for oral cancer targeting, while wheat germ agglutinin (WGA)-conjugated liposomes (DPPC / CHOL / DSPE-PEG-WGA 60:35:5) can deliver amoxicillin to ulcerative lesions.

[0151]

[0139] Cross-linked polymer-caged liposome dental strips provide enhanced structural integrity and controlled release. For example, PC / CHOL (70:30) liposomes can be coated with chitosan (0.2% w / v) and cross-linked with 0.5% glutaraldehyde to encapsulate atorvastatin for antifungal therapy. Soya lecithin / CHOL (80:20) liposomes coated with alginate (0.2% w / v) and cross-linked with calcium chloride can be loaded with miconazole.

[0152]

[0140] Layer-by-layer (LbL) polymer-coated liposome dental strips use alternating layers of oppositely charged polymers for improved stability and sequential drug release. A PC / CHOL (60:40) core can be coated first with chitosan (0.1% w / v), then with alginate (0.1% w / v), encapsulating fluoride and xylitol. Soya lecithin / CHOL (70:30) liposomes can be coated with alternating layers of dextran sulfate and chitosan, loaded with antimicrobial peptides.

[0153]

[0141] Bioadhesive liposome dental strips are formulated for maximum contact with oral tissues. PC / CHOL (65:35) liposomes with chitosan (0.2% w / v) can be loaded with casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) for remineralization. Soya lecithin / CHOL (80:20) liposomes coated with pectin (0.1% w / v) can encapsulate sodium fluoride.

[0154]

[0142] Multi-drug liposome dental strips can deliver combination therapies. PC / CHOL (70:30) liposomes can co-encapsulate doxycycline and chlorhexidine for periodontal therapy, while soya lecithin / CHOL (80:20) liposomes can co-encapsulate fluoride and xylitol for caries prevention and remineralization.

[0155]

[0143] Natural product-loaded liposome dental strips utilize plant-derived actives. PC / CHOL (70:30) liposomes can encapsulate curcumin for anti-inflammatory and antimicrobial effects, and soya lecithin / CHOL (80:20) liposomes can encapsulate green tea polyphenols for antioxidant and antimicrobial oral care.

[0156]

[0144] Strip's arrangement 330 comprising at least one first teeth-binding layer 331 being permeable to flow of dissolved fluoride. The arrangement further comprising at least one second layer 332 with a first high fluoride content encapsulated or otherwise incorporated within pores, mesh or microstructures. Optionally, at least one third layer 333 with a second high fluoride content encapsulated or otherwise incorporated within pores, mesh or microstructures. The first high fluoride content has a first slow-release profile and the second high fluoride content has a second slow-release profile. Additionally, or alternatively, the first profile is provided by first fluoride salt and second profile is provided by second fluoride salt. Fluorapatite (Caio(PO4)eF2) and calcium fluoride (CaF?) are example of the same. Additionally, or alternatively, the first profile is provided at first pH range and second profile is provided at second pH range.

[0157]

[0145] Some biocompatible and non-toxic pH buffers useful in connection with the mouth and oral cavity are e.g., Sodium Bicarbonate, Sodium Phosphate, Citric Acid and Sodium Citrate, Potassium Phosphate, Calcium Carbonate, Magnesium Hydroxide, Lactic Acid and Lactate Salts, Trometamol (Tris), Arginine, Amino Acids (e.g., Glycine, Histidine), Boric Acid, Sodium Acetate, Acetic Acid and Sodium Acetate, Sodium Citrate, Alpha-Lactalbumin, Sodium Salts of Fatty Acids, Glycyrrhizin, Ascorbic Acid, Sodium Sulfate, Calcium Phosphate, Potassium Bicarbonate, and Phytic Acid.

[0158]

[0146] Strip's arrangement 350 comprises at least one first teeth-binding layer 351, permeable to flow of dissolved fluoride. The arrangement further comprising at least one second layer 352 with a first high fluoride content encapsulated or otherwise incorporated within pores, mesh or microstructures; and at least one second layer 352 with a second high fluoride content encapsulated or otherwise incorporated within pores, mesh or microstructures. Those two different layers may have different fluoride release profiles.

[0147] Strip's arrangement 360 comprises at least one first teeth-binding layer 361a being permeable to flow of dissolved fluoride. This layer further comprises or otherwise provided in connection with a rib-like divider 361b, separating between at least one first high fluoride content layer 362 and either (i) the gums, or (ii) providing an effective barrier which avoids fluoride of the 362 layer to react with fluoride-antitoxic compositions in optional layer 363.

[0159]

[0148] Strip's arrangement 370 comprises at least one first teeth-binding layer 370 being permeable to flow of dissolved fluoride. This layer further comprises or otherwise provided in connection with at least one high fluoride content layer 372. This Strip's arrangement further comprises a flexible skirt 373 provided in connection with the gums, physically avoiding dissolved fluoride ions to approach the gums. This skirt-like member is made of any fluoride-impermeable material, such as silicone, polymers, rubber and the like. It is in the scope of the invention wherein this flap comprises at least two layers: gums gluing layer and barrier layer. It is also in the scope of the invention wherein this flap comprises at least three layers: gums gluing layer, barrier layer, and fluoride antitoxic compositions.

[0160]

[0149] It is well in the scope of the invention wherein aforementioned arrangements and derivatives thereof are utilized in a combination.

[0161]

[0150] Reference is still made to Fig. 3, schematically depicting shaped dental strips 380 and 390, whereat strip 380 is monolayer affixed in a symmetrical manner on top at least a portion of the incisal or occlusal sides of a tooth; and strip 390 is an asymmetrical (see symmetry axes 391) multiple layer arrangement as defined in any of the above.

[0162]

[0151] Reference is now made to Fig. 4, showing a side view of jaws. As seen, back teeth (e.g., #16) have smaller crown surface than frontal teeth (see #11). It is hence in the scope of the invention to discloses a shaped dental strip for oral care, wherein the shaped strip is a non-square polygonal member, such as upper strip 401 and somewhat rounded lower strip 402.

[0163]

[0152] Strip 401 is shown in an out-of-scale, and non-limiting manner in scheme 403. The strip is characterized by length 401L, which is function of the length between teeth, e.g., tooth #11 to tooth #16. The strip is also characterized by length a first frontal-width (401FW) and a second rear- width (401RW), which are a function of crown surface of a canine tooth #11 and molar tooth #16. The thickness of the strip is small and presented by 401FW.

[0164]

[0153] Three variants of cross section of width 401FW are further presented. Arrangement 404 comprises at least one first fluoride permeable teeth-binding layer 441, and at least one second layer with high content fluoride 442. Arrangement 405 comprises at least one first fluoride permeable teeth-binding layer 451, and at least one second layer with high content fluoride 453. Divider 452 separates his layer from at least one third fluoride free layer 454. Arrangement 406 comprises at least one first fluoride permeable teeth-binding layer 461; at least one second layer with high content fluoride [type I, of release profile I] 462 and at least one third layer with high content fluoride [type II, of release profile II] 463. Arrangement 406 further comprises a flap 464 incorporated on the gums, configured to avoid fluoride from reaching the gums thus avoiding fluorosis.

[0165]

[0154] FIG. 5 schematically illustrates in an out of scale manner a dental strip according to a preferred embodiment of the present invention; and

[0166] EXAMPLE 1

[0167] Dental Strips for Oral Care Applications

[0168]

[0155] This patent presents innovative options for dental strips designed for various oral care applications, including fluoridation whitening, remineralization, destination and protection. Each layer option provides unique properties and benefits, creating an effective delivery system for active ingredients aimed at improving dental health.

[0169]

[0156] Strips Options:

[0170]

[0157] Hydrogel -Based Layer: This layer utilizes a hydrogel matrix that offers excellent moisture retention and a soothing feel. It can encapsulate active ingredients and deliver them efficiently to the tooth surface, enhancing contact time and efficacy.

[0171]

[0158] Bioadhesive Film Layer: Designed to adhere to the dental surfaces for extended periods, this layer facilitates prolonged delivery of active ingredients. Its bioadhesive properties ensure that the strip stays in place, maximizing the effectiveness of treatments such as fluoride delivery or whitening agents.

[0172]

[0159] Soft Silicone-Based Layer: This option incorporates a soft silicone material that provides flexibility and comfort during wear. The silicone layer can enhance the strip's adhesion to various surfaces in the mouth while ensuring a gentle application that minimizes irritation.

[0173]

[0160] Electrospun Nanofiber Layer: Utilizing advanced electrospinning technology, this layer consists of nanofibers that create a large surface area for effective ingredient delivery. It can also enhance the mechanical properties of the strip and facilitate the controlled release of active components, making it particularly effective for targeted treatments.

[0174]

[0161] Gelatin-Based Film: This biodegradable film layer is made from gelatin, providing a natural option that is easy to apply and remove. It is suitable for delivering active ingredients in a gentle manner, making it an ideal choice for sensitive applications.

[0162] Thermo-responsive Polymers: This innovative layer composition responds to temperature changes in the oral environment, altering its properties based on heat. This feature can enhance comfort and adherence during use, as well as control the release of active ingredients according to the user's body temperature. Light?

[0175]

[0163] Each of these strip options can be combined or modified to create tailored solutions for specific oral care needs. This patent highlights the versatility and efficacy of diverse layers that optimize ingredient delivery while ensuring user comfort and adherence, providing a comprehensive approach to dental health management through the use of strip technology.

[0176] EXAMPLE 2

[0177] Oral Care Formulation

[0178]

[0164] The present patent relates to a novel oral care formulation that includes a blend of active and inactive ingredients aimed at promoting dental health, specifically focusing on the application of fluoride and natural extracts .

[0179]

[0165] The term "therapeutic agent" refers in a non-limiting manner to any active pharmaceutical ingredients (APIs and additives thereof. In a non-limiting manner and as an example, such an API may be selected from one or more of the following:

[0180]

[0166] Sodium Fluoride, USP (1.1% w / v): This active ingredient serves as a source of fluoride ions, which are essential for the prevention of tooth decay and the promotion of enamel remineralization.

[0181]

[0167] Fluoride Ion (1.23%): This is derived from a combination of sodium fluoride (2.09%) and hydrofluoric acid, providing an effective concentration of fluoride ions for enhanced dental protection.

[0182]

[0168] Inactive Ingredients (listed in alphabetical order):

[0183]

[0169] Aloe Vera: Known for its soothing properties, it contributes to oral health by reducing inflammation.

[0184]

[0170] Citric Acid: Acts as a pH regulator and a flavoring agent, enhancing the overall taste of the formulation.

[0185]

[0171] Essential Oils: Included for their antimicrobial properties and flavor enhancement.

[0186]

[0172] Glycerin: Functions as a humectant to retain moisture and contribute to a pleasant mouthfeel.

[0187]

[0173] Green Tea Extract: Rich in antioxidants, it supports overall oral health and may reduce plaque formation.

[0174] Hydroxy ethylcellulose: A thickening agent that improves the texture and stability of the formulation.

[0188]

[0175] Magnesium Aluminum Silicate: Used as a thickening agent that helps improve the consistency of the product.

[0189]

[0176] Phosphoric Acid: This ingredient plays a role in pH adjustment and may aid in remineralization processes.

[0190]

[0177] Polysorbate 20: Serves as an emulsifier to maintain ingredient stability.

[0191]

[0178] Purified Water: The solvent base for the formulation, ensuring proper consistency and application.

[0192]

[0179] Sodium Benzoate: Acts as a preservative to prevent microbial growth.

[0193]

[0180] Sodium Saccharin: A non-nutritive sweetener that improves taste without added calories.

[0194]

[0181] Sorbitol: Serves as a humectant and sweetener, contributing to flavor and texture.

[0195]

[0182] Titanium Dioxide: Used for color and opacity, enhancing the visual appeal of the product.

[0196]

[0183] Xanthan Gum: A thickening agent that helps stabilize the formulation.

[0197]

[0184] Xylitol : This ingredient binds with calcium ions, aiding in the remineralization of tooth enamel, thus contributing to dental health.

[0198]

[0185] Colors: The formulation may contain the following color additives: FD&C Blue No. 1, Green #3, Red #3 and Yellow #5 (Tartrazine)

[0199]

[0186] Flavors: To enhance user experience, the product includes a distinct Mint Flavor, providing a refreshing taste during use.

[0200]

[0187] This innovative formulation harnesses the synergy of active fluoride with natural extracts and effective inactive ingredients, designed to deliver a comprehensive approach to dental care. The combination not only promotes oral hygiene but also improves the overall aesthetic appeal, ensuring high consumer acceptance.

[0201] EXAMPLE 3

[0202] Remineralization Agents for Dental Health

[0203]

[0188] The present patent outlines a unique formulation intended for dental care that emphasizes the use of various remineralization agents. These components work synergistically to restore and enhance tooth enamel, helping prevent and repair early tooth decay.

[0204]

[0189] Remineralization Options:

[0205]

[0190] Calcium Phosphate (0.5% to 5%): This key ingredient provides the essential building blocks necessary for remineralizing tooth enamel. By delivering calcium and phosphate ions directly to demineralized areas of the tooth, it actively helps in rebuilding and strengthening the enamel.

[0191] Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) (10%): Derived from milk, this protein complex stabilizes calcium and phosphate ions, ensuring they remain in a bioavailable form that effectively contributes to enamel remineralization. Its unique structure aids in the repair of early stages of tooth decay, making it an invaluable asset in preventive dental care.

[0206]

[0192] Nano-Hydroxyapatite (2% to 10%): Mimicking the natural mineral component of tooth enamel, this substance fills in micro-cracks and assists in rebuilding enamel at a microscopic level. It is particularly noted for its effectiveness in reducing tooth sensitivity. However, due to regulatory considerations, the use of nano-sized options may not be recommended.

[0207]

[0193] Xylitol (10% to 35%): This natural sugar alcohol has been shown to reduce the growth of bacteria that cause tooth decay. Additionally, xylitol promotes saliva production, which is rich in calcium and phosphate, thereby aiding the remineralization of enamel and enhancing overall oral health.

[0208]

[0194] Sodium Fluoride (0.05% to 0.2%): An essential fluoride source, sodium fluoride serves as a remineralizing agent that helps in the prevention of tooth decay.

[0209]

[0195] Stannous Fluoride (0.4% in gels and 0.454% ): Another fluoride source that not only promotes remineralization but also provides additional benefits such as reducing sensitivity and protecting against gum disease.

[0210]

[0196] Monofluorophosphate (MFP) (0.76%): This fluoride compound contributes to the remineralization process and is a common ingredient in various dental care products.

[0211]

[0197] Tri-calcium Phosphate (TCP) (0.5% to 5%): This compound offers an additional source of calcium, further supporting the remineralization of tooth enamel.

[0212]

[0198] Arginine (1.5%): By neutralizing acids present in the mouth, arginine promotes the natural buffering effect of saliva, enhancing its protective and remineralizing properties.

[0213]

[0199] Phosphates (0.1% to 1.0%): These compounds play a role in the remineralization process by replenishing phosphate levels within the oral environment, further supporting tooth enamel health.

[0214]

[0200] This innovative formulation leverages a combination of biologically relevant and effective remineralization agents to provide a comprehensive solution for enhancing dental health. By targeting the demineralization processes that contribute to tooth decay, this patent aims to empower users with the means to maintain healthy, strong teeth through effective remineralization strategies.

[0215]

[0201] It is well in the scope of the invention wherein the strip comprises or owtheriwse provided in connection with agents used to reduce sensitivity in dental and oral care. The agemts are selected in a non-limiting manner from Desensitizing agents - Contains compounds such as potassium nitrate, strontium chloride, or calcium sodium phosphosilicate to block nerve transmission. Glutaraldehyde - Often found in in-office treatments to seal exposed dentin tubules. Calcium Phosphate Compounds - Such as nano-hydroxyapatite, which helps remineralize enamel. Potassium Nitrate - Commonly used in desensitizing toothpaste to calm nerve endings. Lascaux - A desensitizing agent often used in dental procedures. Resin-Based Sealants - Applied to sensitive areas to provide a protective barrier, and any other agent configured to alleviate tooth sensitivity, whether caused by gum recession, enamel wear, or other dental issues. Always consult with a dental professional for the best treatment options for sensitivity.

[0216] EXAMPLE 4

[0217] Improving Solubility of Fluoride in Enamel

[0218]

[0202] The solubility of fluoride in enamel is significantly influenced by its interaction with calcium and phosphate ions in the oral environment, leading to the formation of two key compounds: fluorapatite (Caio(PO4)eF2) and calcium fluoride (CaF?). The formation of these compounds depends on the pH and concentrations of the respective ionic species present in the solution.

[0219]

[0203] Chemical Mechanisms: When fluoride is introduced into a solution containing calcium and phosphate ions, a three-dimensional solubility isotherm can be plotted, with axes representing calcium concentration, phosphate concentration, pH levels, and fluoride concentrations. This isotherm illustrates the stability conditions for both calcium fluoride and fluorapatite. At higher fluoride concentrations (e.g., 5,000 ppm) [fluoride-containing toothpastes contain concentrations of 1,000 to 1,500 ppm], both fluorapatite and calcium fluoride exhibit stability; however, calcium fluoride formation is favored due to kinetic factors. Alternatively, at lower fluoride concentrations, the solution becomes undersaturated with respect to calcium fluoride, favoring only the formation of fluorapatite.

[0220]

[0204] Dissolution Dynamics: Calcium fluoride has a solubility product constant (pKsp) of approximately 10.5, allowing it to dissolve in aqueous solutions typical of saliva and plaque fluid. Despite this ability to dissolve, calcium fluoride remains relatively stable in the oral environment, primarily due to interactions at the outer surface of its globules with phosphate ions and / or proteins. The dissolution of calcium fluoride is influenced by the pH of the environment, with studies indicating that phosphate can inhibit this dissolution, particularly at pH values below 5.0. This is crucial in the context of caries, as fluoride released from a calcium fluoride reservoir can counteract acid challenges during demineralization events.

[0205] Fluoride Incorporation into Enamel: Fluoride also interacts with hydroxyapatite (HAP) in enamel through two primary mechanisms:

[0221]

[0206] Substitution Reaction: Fluoride can replace hydroxyl ions in the hydroxyapatite crystal lattice, resulting in the formation of a partially fluoridated hydroxyapatite, represented as Caw(PO4)6(OHxFY), where x + y = 2. This mineral transition results in a decrease in solubility, enhancing the acid resistance of enamel.

[0222]

[0207] Precipitation Reaction: Fluoride can also precipitate a fluoridated hydroxyapatite from oral fluids onto existing enamel crystallites, effectively reinforcing enamel integrity.

[0223]

[0208] Kinetic and Thermodynamic Factors: The overall caries preventive effect resulting from fluoride application can be better understood through physicochemical reactions between enamel, mineral ions, and fluoride. While thermodynamic considerations establish the potential for reactions to occur, kinetic factors predominantly dictate the rate at which these reactions proceed. For instance, while fluoride theoretically accelerates the precipitation of apatite minerals, the real-world oral environment may present challenges such as protein absorption that hinder crystal formation.

[0224]

[0209] Fluoride Reservoir Effect: The cariostatic effect of fluoride has traditionally been attributed to its incorporation into the hydroxyapatite crystal lattice, resulting in reduced solubility and enhanced resistance to demineralization. However, recent research indicates that a continuous supply of fluoride ions may have a more significant influence on caries susceptibility than the intrinsic fluoride content of the enamel or root cementum itself. Studies aligning with this observation suggest that topical applications of fluoride may offer substantial caries protective effects, possibly greater than those achieved by fluoride uptake alone.

[0225]

[0210] The present invention provides means and methods for increasing fluoride solubility in enamel can be approached through several methods that focus on optimizing the chemical environment and enhancing fluoride incorporation into the enamel structure.

[0226]

[0211] According to one embodiment of the invention, the dental strips of the present invention adjust optimal pH. Hence, acidic environment is maintained so that a slight acidic environment (pH around 4.5 to 5.5) promotes the formation of soluble fluoride compounds like calcium fluoride (CaF?). An acidic pH encourages fluoride to remain stable in solution and may enhance the release of fluoride ions into the enamel. Additionally, or alternatively, buffering agents are used. The buffers help maintain the ideal pH levels. For example, formulations that include phosphate ions may help stabilize the fluoride concentration in an acidic environment, allowing for enhanced fluoride uptake.

[0212] According to another embodiment of the invention, the dental strip of the present invention comprises acidulated fluoride gels. The incorporation of acidulated phosphate fluoride (APF) gels containing 1.23% fluoride enhance fluoride solubility. The acidification helps to solubilize fluoride and facilitates the interaction between fluoride and enamel.

[0227]

[0213] According to another embodiment of the invention, the dental strip of the present invention is of high fluoride concentrations. This is useful for delivering fluoride at higher concentrations (up to 5% NaF in varnishes) can increase the availability of fluoride ions, thus enhancing uptake into the enamel and improving caries resistance.

[0228]

[0214] According to yet another embodiment of the invention, the dental strip of the present invention ate utilizable in a method of sustained exposure. Prolonged exposure to strips of the present invention allows more time for fluoride ions to interact with the enamel surface, increasing the potential for incorporation into the hydroxyapatite lattice. Extended application times ensure higher fluoride concentrations in the oral environment.

[0229]

[0215] According to another embodiment of the invention, the dental strip of the present invention incorporates Enhancing Agents. Hence for example, strip comprises a combination with Casein Phosphopeptide- Amorphous Calcium Phosphate (CPP-ACP). The strips containing CPP-ACP have been shown to enhance remineralization effects. The combination of fluoride with these agents can help create an environment conducive to increased fluoride solubility and retention in enamel. Additionally, or alternatively, strips comprise carboxymethyl cellulose or similar thickening agents that enhance the viscosity of fluoride gels, allowing for better adherence to tooth surfaces and prolonged fluoride availability at the enamel interface.

[0230]

[0216] According to another embodiment of the invention, the dental strip of the present invention is utilized for fluoride reservoir formation, thus encouraging the formation of calcium fluoride in the oral environment serves as a fluoride reservoir. The strips comprise compositions that dissolve under acidic conditions (e.g., during acid challenges) to gradually release fluoride ions, thereby reinforcing the enamel continually.

[0231] EXAMPLE 5

[0232] The Role of Selenium-Containing Materials in Oral Care and Dentistry

[0233]

[0217] The present invention also relates to the field of oral care and dentistry, specifically the utilization of selenium-containing materials in products designed for the prevention and treatment of oral diseases, the enhancement of oral health, and the promotion of overall dental hygiene.

[0218] Oral health is a critical component of overall health, and the prevention of oral diseases, such as dental caries, gingivitis, and periodontitis, is essential. Traditionally, oral care products have focused on ingredients with antibacterial, anti-inflammatory, and remineralizing properties. Recent research has identified selenium, an essential micronutrient known for its antioxidant properties and role in the immune system, as a valuable component for enhancing oral health.

[0234]

[0219] The invention further introduces various selenium-containing materials and their applications in oral care products such as toothpaste, mouthwashes, dental gels, and dietary supplements. These materials exhibit beneficial effects due to selenium’s properties, including its ability to promote antioxidative mechanisms, enhance immune function, and modulate inflammatory responses.

[0235]

[0220] It is in the scope of the invention wherein Selenium Compounds and Sources: are selected in a non-limiting manner formn Sodium Selenite: A sodium salt of selenious acid, which has been shown to possess antimicrobial properties and can be incorporated into dental formulations to enhance their efficacy against oral pathogens. Selenium-Enriched Yeast and extracts thereof.

[0236]

[0221] A natural source of selenium that can be utilized in dietary supplements to promote systemic immune health, thereby supporting oral health. Selenomethionine: An amino acid form of selenium that can be included in oral health products to provide both antioxidant protection and antimicrobial properties.

[0237]

[0222] Strip coating Formulations: Incorporating selenium compounds into strips and the like enhances the product’s antibacterial properties, aiding in the reduction of plaque formation and gingivitis. Selenium's antioxidant properties can also protect oral tissues against oxidative damage.

[0238]

[0223] Antioxidative Effects: Selenium contributes to the activity of glutathione peroxidase and other antioxidant enzymes, reducing oxidative stress in oral tissues and promoting cellular health.

[0239]

[0224] Anti-Inflammatory Properties: Selenium-containing materials can modulate inflammatory pathways, thereby aiding in the management of inflammatory periodontal diseases.

[0240]

[0225] Immune System Support: By enhancing systemic immunity, selenium plays a role in the body ’ s ability to resist oral infections and promote healing.

[0241]

[0226] Potential Benefits: The integration of selenium-containing materials in oral care products presents a multi-faceted approach to oral health, offering significant advantages such as: Enhanced protection against dental caries and periodontal diseases. Improved healing and recover}? in oral tissues. Support for immune function, thereby reducing the incidence of oral infections.

[0227] The present invention hence highlights the therapeutic potential of selenium -containing materials in the field of oral care and denti stry. By leveraging the unique properties of selenium, these materials can enhance the efficacy of oral care products, contribute to improved oral health outcomes, and support overall health. Further research and development in this area can lead to innovative oral health solutions that benefit a wide range of consumers.

[0242]

[0228] The present invention further discloses, according to one of its embodiments, a dental product comprising one or more selenium-containing materials for the prevention and treatment of oral diseases.

[0243]

[0229] The present invention also discloses, according to yet another embodiment, a method of enhancing oral health using selenium -based compounds in dental formulations.

[0244] EXAMPLE 6

[0245] Dental Strips for Fluoride Delivery and Remineralization

[0246]

[0230] The present invention is also relating to dental strips designed for the effective delivery of fluoride and remineralization agents, aimed at enhancing oral health by promoting enamel strength and preventing dental caries.

[0247]

[0231] It is in the scope of the invention wherein the dental strips comprise three distinct layers: an outer layer for support and adhesion, a supporting layer that is soft and foamy to deliver fluoride and remineralization agents, and an internal layer designed for optimal fluoride release. Each layer plays a critical role in ensuring the strips adhere well to teeth while maintaining integrity and functionality.

[0248]

[0232] In one embodiment of the invention, the layers of the dental strips are as follows: Dental Strips for Fluoride Delivery and Remineralization Outer Layer:

[0249]

[0233] This layer provides structural support and adhesion to the teeth. The material options include: Polyethylene (PE) or Polypropylene (PP) Film: These materials are chosen fortheir flexibility and strength, providing a durable yet adaptable base for the dental strip. Ethylene Vinyl Acetate (EVA): Known for its flexibility and biocompatibility, EVA can be engineered to adhere to both wet and dry surfaces, ensuring reliable application. Hydrocolloid-Based Adhesives: These materials enhance adhesion, especially in moist environments, helping to maintain contact with tooth surfaces during application. Application Methods are e.g., as follows: Adhesives can be applied using spray coating or lamination processes, offering versatility in manufacturing.

[0250] Supporting Layer:

[0234] This soft and foamy layer contains fluoride and remineralization agents, providing cushioning and conformability, ensuring excellent contact with the contours of the teeth, including interdental spaces. The creation of this layer involves:, e.g., Polyurethane Foam: Offers softness and adaptability, allowing for the infusion of active ingredients. Polyvinyl Alcohol (PVA) Foam: Biocompatible and water-soluble, often utilized in wound dressings and medical applications. Hydrophilic Polyurethane Foam: Facilitates moisture absorption, allowing even distribution of fluoride and remineralization agents onto tooth surfaces and within cavities. Examples of Active Ingredients are e.g., Fluoride Compounds: Sodium fluoride, Stannous fluoride, Amine fluoride. Remineralization Agents: Calcium phosphate (0.5% to 5%), Tri-calcium phosphate (TCP) (0.5% to 5%), Hydroxyapatite, Xylitol (10% to 35%), Casein phosphopeptides (CPP), Calcium Citrate, and Magnesium Phosphate.

[0251] Internal Layer:

[0252]

[0235] This layer directly contacts the teeth and is crucial for maximizing fluoride delivery and enhancing remineralization. The manufacturing process can involve solution casting or film extrusion. The materials can include, e.g., Gelatin-Based or Hydrogel Film: These hydrogels can be loaded with fluoride and calcium phosphate compounds, softening upon contact with saliva to enhance adhesion and facilitate active ingredient release. Chitosan Film: Biocompatible with inherent adhesive properties, enhancing fluoride delivery and promoting oral health. Poloxamer Gel / Film: Thermosensitive polymer films that, when combined with active ingredients, provide controlled and gradual fluoride release. Examples of Active Ingredients are as follows: Sodium fluoride, Calcium phosphate, Hydroxyapatite, Fluorhydroxyapatite, Calcium Bicarbonate, and Sodium Citrate. Overall Manufacturing Options: The three layers can be laminated together using heat or pressure-sensitive adhesives, ensuring their cohesive integration. Fluoride and remineralization agents can be applied to the foam or film layers through spray coating or dip coating methods. Subsequently, after assembly, the dental strips can be die-cut into shapes that conform to the upper and lower teeth, ensuring optimal fit and effectiveness during use.

[0253]

[0236] Additional Examples for Production and Use of Dental Strips: Flavored Strips: Incorporation of flavoring agents, such as natural mint extract, cinnamon, or bubblegum flavor, to improve user compliance and make fluoride application more appealing. Biodegradable Strips: Utilizing natural polymers such as pullulan or alginate for the production of eco-friendly dental strips that break down overtime, leaving no environmental footprint. Medicated Strips: Incorporating therapeutic agents like potassium nitrate or arginine in addition to fluoride to alleviate tooth sensitivity while providing remineralization benefits. Customized Strips: Development of customized strips designed through 3D printing technology, which can ensure a perfect fit based on individual dental impressions, improving the effectiveness of fluoride delivery. DualAction Strips: Creation of dual-action strips that release both fluoride and xylitol to not only remineralize but also inhibit bacteria.

[0254] EXAMPLE 7

[0255] Bioadhesives

[0256]

[0237] Bioadhesives films that are useful as layers for ensuring prolonged contact with tooth surfaces:

[0257]

[0238] Chitosan Films - Derived from chitin, known for its biocompatibility and bioadhesive properties.

[0258]

[0239] Gelatin Films - Biodegradable and hydrophilic, providing good adherence to mucosal surfaces.

[0259]

[0240] Polyvinyl Alcohol (PVA) Films - Biocompatible and can form flexible and strong films.

[0260]

[0241] Sodium Alginate Films - Formed from alginic acid, known for its gel-forming ability and adhesive properties.

[0261]

[0242] Polylactic Acid (PLA) Films - Biodegradable and used for sustained release of active ingredients.

[0262]

[0243] Hyaluronic Acid Films - Known for its water retention and mucoadhesive properties.

[0263]

[0244] Carbopol Films - A type of polymer that can create mucoadhesive films with thickening properties.

[0264]

[0245] Pectin Films - Naturally occurring polysaccharides that can form bioadhesive films.

[0265]

[0246] Polycaprolactone (PCL) Films - Biodegradable with good mechanical properties for sustained drug release.

[0266]

[0247] Ethyl Cellulose Films - Used for controlled release and enhancing adhesion to tooth surfaces.

[0267]

[0248] list of bio-adhesive films used for prolonged contact with tooth surfaces, including additional examples of chemical compositions for each type: Chitosan Films (including Chitosan-based mouthwash films, Chitosan / gelatin composite films, Chitosan / sodium alginate films, Chitosan- based antimicrobial films), Gelatin Films (including Gelatin-based drug delivery films, Gelatin / Chitosan films, Gelatin / alginate films, Gelatin-based mucoadhesive films). Polyvinyl Alcohol (PVA) Films (including PVA-based oral patches, PVA / Chitosan films, PVA / hyaluronic acid films, PVA / PEG films), Sodium Alginate Films (including Sodium alginate dental gels, Sodium alginate / gelatin films, Sodium alginate / Chitosan films, Sodium alginate-based mucoadhesive films), Polylactic Acid (PLA) Films (including PLA-based bioactive films, PLA'Polyethylene glycol (PEG) films, PLA'chitosan films, PLA with natural extracts), Hyaluronic Acid Films (including Hyaluronic acid-containing dental films, Hyaluronic acid / Chitosan films. Hyaluronic acid / gelatin films, Hyaluronic acid-based mucoadhesive films), Carbopol Films (including Carbopol-based topical gels, Carbopol / poly vinyl pyrrolidone (PVP) films, Carbopol / hyaluronic acid films, Carbopol / Chitosan films), Pectin Films (including Pectin-based oral care films, Pectin with Calcium ions films, Pectin / Gelatin films, Pectin-based drug deliver}'- films), Polycaprolactone (PCL) Films (including PCL-based slow-release films, PCL with hydroxyapatite films, PCL / PLGA (Poly(lactic-co-glycolic acid)) films, PCL-based antimicrobial films), Ethyl Cellulose Films (including Ethyl cellulose matrices in drug delivery systems, Ethyl cellulose / PEG films, Ethyl cellulose / chitosan films, Ethyl cellulose / hydroxypropyl methyl cellulose (HPMC) films).

[0268] EXAMPLE 8

[0269] Kits

[0270]

[0249] The present invention relates to advanced dental care products, specifically to a dental strip kit designed for effective delivery of fluoride and remineralization agents to enhance oral health across different age groups, including toddlers, children, and elderly individuals. The kit is engineered to include multiple components that facilitate ease of use, effective application, and improved maintenance of dental health. The implementation of varying concentrations of active ingredients across different periods ensures tailored oral care regimens, allowing users to receive intensive treatment when necessary and lower- strength treatments during maintenance phases.

[0271]

[0250] The following set of components will ensure that the dental kit is not only functional and effective but also convenient, safe, and easy for patients to use in both clinical and home settings.

[0272]

[0251] The core component of the kit is the dental strip itself. It is composed of multiple layers designed to deliver fluoride and remineralization agents to the teeth. The lower layer provides the structural support and adhesive properties, allowing the strip to stick to the teeth securely. The middle layer, foamy and soft, facilitates penetration into the cavities and micro-grooves of the teeth while carrying fluoride and calcium phosphate for enamel strengthening. The uppermost layer contains the active ingredients, such as sodium fluoride and CPP-ACP, that help to remineralize and protect the teeth from further decay.

[0273]

[0252] Clear and detailed instructions are essential to ensure the proper application and effectiveness of the dental strip. The Instructions For Use (IFU) will outline each step, from how to prepare the strip for application to proper placement on the teeth. It will also provide information on how long to leave the strip on and any post-use guidelines. The IFU must be written in a patientfriendly language, ensuring that users understand how to apply the strip safely and effectively. This document will also contain any necessary precautions, warnings, and storage instructions.

[0274]

[0253] To improve ease of use and hygiene, the kit will include a specialized application tool. This tool is designed to help patients apply the strip to their teeth more easily, reducing the risk of contamination and ensuring the strip adheres properly. The tool could be a small spatula or handle that allows users to press the strip firmly against their teeth without using their fingers, ensuring an even application and optimal contact between the strip and tooth surfaces.

[0275]

[0254] The dental kit will include a compact and durable storage case for convenient and hygienic storage of the strips, especially if the strips are reusable or come in a multi-use format. The case will be designed to keep the strips protected from moisture, light, and contamination, which can degrade their effectiveness. This case can also house other components of the kit, keeping everything organized for the user.

[0276]

[0255] To ensure that the strip stays securely in place during use, the kit will provide an additional adhesive or retention component. This may come in the form of a separate adhesive gel or retention bands that help the strip adhere more securely to the teeth. This component ensures that the strip remains in the correct position during application, allowing for prolonged and uninterrupted delivery of the active ingredients.

[0277]

[0256] A small, user-friendly timer will be included in the kit to help patients accurately track the application time. The effectiveness of the dental strip depends on it remaining in contact with the teeth for a specific duration. The timer will allow patients to follow the recommended treatment time, ensuring they don’t remove the strip too early or leave it on for too long, which could affect both safety and efficacy.

[0278]

[0257] After using the strip, patients may need a post-treatment product to enhance the effectiveness of the strip or soothe the mouth. This could include a mouthwash or gel that provides additional fluoride or helps soothe the gums. The post-use care product will support continued protection against cavities and promote enamel remineralization while ensuring patient comfort.

[0279]

[0258] To prepare the teeth for the strip application, the kit may include a pre-use care product, such as a cleansing mouthwash or a primer gel. This product would help remove plaque, food particles, and surface debris from the teeth, ensuring the strip adheres properly and that the active ingredients can penetrate the tooth surfaces more effectively.

[0280]

[0259] Along with the IFU, the kit will include comprehensive safety information. This will cover any potential side effects, contraindications, and warnings about the proper and improper use of the product. It will inform patients of any risks associated with the use of the dental strip, such as potential allergic reactions, as well as any situations where the product should not be used (e.g., in patients with certain dental conditions). The safety information ensures that patients are fully informed and can use the product confidently and safely.

[0281]

[0260] It should be understood that the dental strip of the present invention can include any numberor types of features shown and described with respect to the strips shown in the figures herein. It should also be understood that all of the strips shown and described herein can be cut in half, preferably generally around the mid-point, and either half may then be used alone to accomplish its function as described above.

[0282]

[0261] The core component of the kit is the dental strip itself, constructed from multiple polymeric layers optimized for dental use. The kit contains age-specific applications to cater to the unique needs of different age groups while ensuring safety and efficacy. Integrated communication means improve the overall experience, offering real-time feedback and a structured regimen to support optimal oral health. This invention also incorporates strips with varying concentrations of active ingredients over designated periods, allowing for an adaptable and effective treatment strategy.

[0283] Example 8A: Advanced Remineralization Kit Composition for Adults:

[0284]

[0262] Lower Layer: Strong adhesive polymer, such as polyvinyl acetate (PVA).

[0285]

[0263] Middle Layer: Open-cell polyurethane foam designed for ingredient delivery.

[0286]

[0264] Upper Layer (High Concentration Phase): 1.5% sodium fluoride and 3% casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) for intensive remineralization, during the first two weeks of use each month (Days 1-14).

[0287]

[0265] Upper Layer (Maintenance Phase): 0.5% sodium fluoride and 1% CPP-ACP during the latter two weeks of the month (Days 15-30). This gradual reduction encourages ongoing maintenance of oral health without overwhelming sensitivity.

[0288]

[0266] Monthly Schedule: Each strip is labeled with specific days, indicating high-concentration use days and lower concentration use days (e.g., “Days 1-14: Intensive Treatment,” “Days 15-30: Maintenance”).

[0289] Example 8B: Kid-Friendly Dental Strip Kit Composition for Children (Ages 5-12):

[0290]

[0267] Lower Layer: Child-friendly thermoplastic elastomer for flexibility.

[0291]

[0268] Middle Layer: Calcium phosphate gel for adherence and gentle protection.

[0269] Upper Layer (High Concentration Phase): 0.7% sodium fluoride and 1.5% calcium phosphate for the first half of each month (Days 1-15).

[0292]

[0270] Upper Layer (Lower Concentration Phase): 0.3% sodium fluoride and 1% calcium phosphate for the second half (Days 16-30), ensuring that children receive the necessary support without excessive fluoride exposure.

[0293]

[0271] Monthly Schedule: Brightly colored stickers for kids indicating when to use each strip (e.g., “Use on Day 5 for Intensive Care,” “Use on Day 20 for Gentle Maintenance”).

[0294] Example 8C: Toddler Dental Strip Kit (Ages 2-5)

[0295]

[0272] Compositions

[0296]

[0273] Lower Layer: Bio-compatible, soft adhesive polymer designed for sensitive gums.

[0297]

[0274] Middle Layer: Silica gel with a very low fluoride concentration (0.1%).

[0298]

[0275] Upper Layer: Alternating concentrations, with higher concentrations of natural fluoride extracts (0.2%) during the first half of the month for enhanced protection (Days 1-15), and lower concentrations (0.1%) for the latter half (Days 16-30) to maintain safety for developing enamel.

[0299]

[0276] Monthly Schedule: Illustrated cards that suggest days for specific benefits, with special notes (e.g., “Use on Day 10 for Extra Protection” vs. “Use on Day 25 for Gentle Use”).

[0300]

[0277]

[0301]

[0278] Example 8D: Whitening and Remineralization Combo Kit for Adults (Ages 18+)

[0302]

[0279] Composition:

[0303]

[0280] Lower Layer: Medical-grade polyester netting.

[0304]

[0281] Middle Layer: Calcium phosphate combined with sodium bicarbonate.

[0305]

[0282] Upper Layer (Intense Whitening Phase): 4% hydrogen peroxide, combined with 1% sodium fluoride during the first half of the month for maximum stain removal (Days 1-15).

[0306]

[0283] Upper Layer (Maintenance Phase): Reduced concentration of 2% hydrogen peroxide and 0.5% sodium fluoride in the latter half of the month (Days 16-30) to maintain whitening effects without excessive enamel wear.

[0307]

[0284] Monthly Schedule: Users have clear indications for treatment intensity based on the day, with QR codes linking to educational content on maintaining oral health during both phases.

[0308] EXAMPLE 9

[0309] Strips with auxiliaries

[0285] It is according to an embodiment of the invention wherein various auxiliaries are added to, comprised or provided in connection with dental strips of the present invention. Auxiliaries are selected in a non-limiting manner from fixating means, manipulating means and handling means, such as "earring"-like member 502 in connection with a U-shape strip 501, see figure 5. Auxiliaries are also selected in a non-limiting manner from a group consisting of color marks, e.g., for marking inner and outer sides of the strip or portion thereof, barcodes, and QR codes, X ray readable markers and any other marker in use in oral care; sensors and indicators, such as pH-indicators, time-of-use indicators, expiration-date indicators, sugar-indicators, medicament-indicators, inflammatory- and microbial-indicators, etc. Auxiliaries are also selected in a non-limiting manner from a group consisting of communication means, such as RFID and the like.

[0310] EXAMPLE 10

[0311] Sodium Fluoride (NaF) Release Profile from Erodible PVA / CMC / HPMC Dental Strips:

[0312]

[0286] Dissolution Testing and Operational Principles

[0313]

[0287] It is in the scope of the invention wherein the strip as disclosed herein may feature at least one therapeutic-agent-rich portion (TARP) and at least one portion with significantly lower TARP content, allowing for localized, sustained release of active ingredients while minimizing exposure to sensitive areas such as the gums. The invention further describes multilayered and customizable strip constructions, including bioadhesive films and foamy or hydrogel layers, to optimize adhesion, comfort, and efficacy. The strips may be incorporated into comprehensive dental kits with application tools, timers, storage cases, and detailed instructions, and are suitable for use across various age groups and oral health needs. The patent emphasizes the strip’s ability to provide effective caries prevention, remineralization, and antibacterial action, while also addressing safety, user compliance, and the potential for integration with other oral care agents and technologies.

[0314]

[0288] US2012322024 discloses of a dental strip designed for application to the front teeth and / or gums, which is made from a chemically inert, flexible, hydrophilic material such as polyurethane, polyester, polyethylene, or cellulose. The strip is configured to deliver oral care compositions-such as multi-carboxylate salts, teeth whitening agents, fluoride, antimicrobials, anti-inflammatories, nutrients, antioxidants, and other oral health agents-to targeted areas of the teeth and gums. The strip can be engineered to provide controlled and sustained release of these active ingredients, including the possibility of a concentration gradient along the strip, and may be used in combination with dental devices like troughs or braces to enhance treatment effects. The invention aims to improve oral care by enabling precise, comfortable, and effective delivery of therapeutic agents, while minimizing discomfort and unwanted spread of active substances within the oral cavity.

[0315]

[0289] US2012322024 teaches of a film / strip capable of providing a controlled gradient of active ingredient concentration along or across it, this feature made possible due to the fact that the film material is based on a water-insoluble polymer, for example: polyurethane foams, polyesters, polyethylene, cellulose, etc.. Despite its hydrophilic nature, this material allows controlled release according to a diffusion mechanism.

[0316]

[0290] US2013266914 discloses an oral care device in the form of a strip designed to transfer a therapeutic dental composition-such as tooth whiteners, antimicrobials, tartar control agents, or protectants - directly onto the surface of teeth or gums. The device consists of a flexible, generally water-insoluble backing layer coated on one side with a discontinuous micro-pattern (e.g., dots or islands) of a solid or semi-solid therapeutic composition. This design enables the selective transfer and adhesion of the therapeutic composition to the hard surfaces of the teeth, while minimizing unwanted deposition on soft tissues, and allows for controlled release of the active agents. The strip can be used by pressing it against the teeth, after which the backing layer may be removed, leaving the therapeutic composition in place. The invention aims to provide a more convenient, effective, and targeted method for delivering dental treatments without the need for cumbersome trays or continuous gels, and addresses issues of patient comfort, efficacy, and safety during application.

[0317]

[0291] In US2013266914 the therapeutic composition applied to the backing layer can be formulated with water-soluble carriers, and the patent specifically discusses that the carrier for the therapeutic agent may be water-insoluble, water-resistant, or water-soluble. The solubility of the carrier in water (or saliva) is highlighted as a key factor influencing the residence time of the fdm on the teeth, with highly water-soluble carriers dissolving rapidly in the oral cavity to release the therapeutic agent quickly. Preferred embodiments include carriers with limited water solubility for prolonged release, but the patent clearly contemplates and enables the use of water-soluble materials as part of the device’s design

[0318]

[0292] In contrast to US2012322024, US2013266914 uses water-soluble materials such as PVA that dissolve rapidly in aqueous environments such as saliva, and therefore cannot maintain a concentration gradient throughout the application period. This fundamental difference in material properties leads to the conclusion that the devices of US2012322024 and US2013266914 cannot be substituted without compromising the core functionality of US2012322024. Therefore, a person skilled in the art would not combine these two sources, as such a combination would negate the central advantage taught by US2012322024. The ability to maintain a concentration gradient during application constitutes a key functional characteristic in US2012322024’s invention, while US2013266914’s materials would inherently eliminate this functionality. Such a combination would alter the operating principle of the device in US2012322024, and according to established principles in patent law, a modification that leads away from the teaching of US2012322024cannot be considered obvious for a skilled professional. US2012322024's operation depends on the insolubility of the material, while US2013266914's materials negate this capability.

[0319]

[0293] In yet another sets of embodiments, sodium fluoride (NaF) releasing strips of the present invention comprise a formulation where the film is primarily composed of polyvinyl alcohol (PVA), carboxymethyl cellulose (CMC), and hydroxypropyl methyl cellulose (HPMC), each contributing to a distinct function within the strip. PVA acts as the film-forming polymer, providing the structural matrix necessary for the strip’s integrity. CMC serves as a mucoadhesive agent, enhancing the adhesion of the strip to the mucosal surfaces, while HPMC functions as a film strength enhancer and dissolution promoter, facilitating the controlled release of NaF as the polymer matrix erodes in the aqueous medium.

[0320]

[0294] In another embodiment, the NaF release rate is manipulated by adjusting the thickness of the polymeric film. The release is substantially faster in thinner films, ranging from 80 to 150 μm, due to more rapid surface erosion compared to thicker films, such as those in the 300 to 350 μm range. The erosion-driven release mechanism ensures a linear release trend over time, aligning with a zero-order kinetic model where the release rate remains constant across the duration of the dissolution process, specified by the equation Mt = k x t, where Mt is the cumulative amount of NaF released at time t.

[0321]

[0295] In yet another embodiment, additional formulation components may include glycerin, which is incorporated as a plasticizer, constituting approximately 10% w / w of the total polymer content, with propylene glycol serving as a co-plasticizer that may be substituted with glycerol. Sweetening agents such as sucralose or stevia, and xylitol, which also provides anti-cavity benefits, are included to enhance palatability. Flavor enhancements provided by mint or spearmint, along with polysorbate 80 as a surfactant, citric acid, and trisodium citrate for pH adjustment, and sodium benzoate as a preservative, further contribute to the overall composition, thereby ensuring both functionality and consumer acceptance of the NaF- releasing strips.

[0322]

[0296] Fig. 6 illustrates the cumulative release profile of sodium fluoride (NaF) from erodible strips composed of polyvinyl alcohol (PVA), carboxymethyl cellulose (CMC), and hydroxypropyl methylcellulose (HPMC) with varying film thicknesses over time. The y-axis represents the cumulative NaF release as a percentage, while the x-axis denotes time in minutes. The graph includes three distinct curves corresponding to differing film thicknesses: thin film sample, medium thickness film sample, and thick film sample.

[0323]

[0297] The curve for the thin film sample exhibits the most rapid release rate, approaching nearly 100% cumulative NaF release within a shorter duration compared to the other samples. This data indicates that the erosion-based release mechanism is influenced by film thickness, with thinner films dissolving more rapidly in the medium, resulting in accelerated NaF release.

[0324]

[0298] Conversely, the curve representing the thick film sample demonstrates a slower release rate, necessitating a longer period to achieve a similar level of NaF release. The medium thickness film sample displays an intermediate release rate. The differing release profiles support the erosion-controlled release mechanism, where the disintegration speed of the polymer matrix correlates with film thickness.

[0325]

[0299] Key characteristics of the erosion-based release profile for the strips are as follows:

[0326]

[0300] No Burst Effect: The absence of an initial rapid NaF release distinguishes it from diffusion- driven release.

[0327]

[0301] Linear Release Trend: The cumulative release increases proportionately with time.

[0328]

[0302] Controlled Delivery: Release occurs uniformly, governed solely by polymer degradation and mechanical erosion in the buffer.

[0329] Zero-Order Release Equation: Mt = k • t

[0330]

[0303] Mt represents the cumulative amount of NaF released at time t (mg / min or % / min).k is the erosion rate constant (mg / min or % / min).t denotes time (min).

[0331]

[0304] At t = Two (when complete release is achieved), Mt = Mtotal, thus: k — Mtotal / T100

[0332]

[0305] For instance, if full release (100%) occurs at 2 minutes, k is calculated as 100% / 2 = 50% NaF release per minute, yielding a predicted release profile: Mt = 50 • t

[0333]

[0306] First-Order Release (Concentration-Dependent): The release rate is proportional to the remaining drug concentration, following an exponential decay pattern where release is more rapid initially and decelerates over time. This model is generally observed in oral drug formulations adhering to Noyes-Whitney kinetics.

[0334]

[0307] Factors Influencing Release: Polymer degradation rate: Increased degradation results in faster release.

[0308] Water solubility of the polymer: Highly water-soluble polymers such as HPMC, PVA, and CMC expedite active ingredient release due to bulk erosion.

[0335]

[0309] Film thickness: Thicker films require extended times to completely dissolve.

[0336] Dissolution Test:

[0337]

[0310] Dissolution Method: The NaF-releasing strips were evaluated using a USP dissolution apparatus. Each sample was precisely weighed prior to testing, with cumulative release calculated as a percentage.

[0338]

[0311] The setup was conducted as follows: Apparatus: USP Type II (Paddle Apparatus), Medium: Phosphate buffer solution (pH 6.8), Temperature: 37 ± 0.5°CStirring Speed: 50 rpmSampling Intervals: 5, 10, 15, 20, 30, 40, 50, and 60 minutesAnalytical Method: Ion-Selective Electrode (ISE) for fluoride quantification

[0339]

[0312] NaF Release Profile: The accompanying graph details the cumulative NaF release from film samples of varying thicknesses.

[0340]

[0313] In accordance with the description, the sodium fluoride (NaF) release from the dental strips is not governed by diffusion. This release is characterized by an erosion-controlled mechanism, in which the active pharmaceutical ingredient (API) is liberated as a result of the gradual degradation or dissolution of the polymeric matrix in the surrounding medium.

[0341]

[0314] This erosion-controlled release ensures that the release profile is dictated solely by the mechanical erosion and degradation of the polymers, namely polyvinyl alcohol (PVA), carboxymethyl cellulose (CMC), and hydroxypropyl methyl cellulose (HPMC), which are highly water-soluble. These polymers dissolve at a consistent rate when exposed to the aqueous environment, allowing NaF to be released uniformly without the involvement of significant diffusion processes from the intact polymer matrix.

[0342]

[0315] Consequently, the cumulative release of NaF exhibits a linear relationship with time, aligning with zero-order kinetics, or a first-order kinetic model where applicable. This results in a controlled release profile that is devoid of any initial burst effect typically associated with diffusion-driven release systems. The polymer matrix composition and thickness are crucial in modulating the release rate since the degradation rate and subsequent NaF release are faster in thinner films and slower in thicker films.

[0343]

[0316] As further described, a dental strip for oral care comprises a surface characterized by containing:

[0344]

[0317] This strip includes a formulation for enhanced drug delivery in dental care and may consist of various components such as amphiphilic block copolymers, ethosomes, liposomes, microemulsions, nanostructured lipid carriers, nanoemulsions, self-emulsifying drug delivery systems, solid lipid nanoparticles, and transferosomes, facilitating non-diffusion based NaF release upon erosion of the polymer matrix.

[0345]

[0318] Table 1 : Composition Utilized for Non-Diffusion Release of Fluorine and Functional

[0346] Attributes of the Oral Care Dental Strip's Surface

[0347]

[0319] Table 1 provides in a non-limiting manner an illustrative depiction of a dental strip for oral care. Fig. 6 highlights the structural composition of the strip's surface, which is distinguished by the presence of both:

[0348]

[0320] Fig. 6 demonstrates that the formulation for enhanced drug delivery in dental care is dissolved in a non-diffusion manner.

[0321] Additionally, a detailed depiction of the formulation shows the inclusion of the following components:

[0349]

[0322] Sodium fluoride (NaF) as the active ingredient.Polyvinyl alcohol (PVA) as a film-forming polymer. Carboxymethyl cellulose (CMC) functioning as a mucoadhesive. Hydroxypropyl methyl cellulose (HPMC) serving as a film strength and dissolution enhancer.

[0350]

[0323] Optionally, the formulation may also comprise: Glycerin, approximately 10% w / w of the total polymer content, as a plasticizer. Propylene glycol, which can be replaced with glycerol, as a co-plasticizer. Sweetening agents such as sucralose or stevia. Xylitol as both a sweetener and an anti-cavity agent. Flavor enhancements through mint or spearmint. Polysorbate 80 functioning as a surfactant. Citric acid and trisodium citrate as pH adjusters. Sodium benzoate is served as a preservative. Deionized water acting as the solvent.

[0351]

[0324] The configuration depicted in the figure underscores a non-diffusion release mechanism, central to the efficacy of the strip's enhanced drug delivery system.

[0352]

[0325] Generally, HPMC (Hydroxypropyl Methylcellulose) comes in different viscosity grades, which are usually defined by their apparent viscosity (measured as a 2% w / w aqueous solution at 20 °C). The grades are often designated by numbers and letters that indicate substitution type and viscosity. Typical range for low viscosity HPMC: 3-50 mPa s (2% solution). Below ~20 mPa- s is usually considered as “low viscosity,” good for forming clear, uniform, fast-dissolving films (like the NaF strip according to the present invention). Above -100 mPa s, medium to high viscosity, is more suited for gels or thick coatings and much less NaF strip according to the present invention.

[0353]

[0326] Below are some examples of low-viscosity (LV) HPMC grades (commonly used in films, coatings, and drug delivery) which may be used in the NaF releasing strip according to the present invention:

[0354]

[0327] Commercially available Methocel by Dow and DuPont) including Methocel E3 Premium LV (-3 mPa s), Methocel E5 Premium LV (-5 mPa s), Methocel El 5 LV (-15 mPa s), and Methocel E50 LV (-50 mPa s). (E-type- higher methoxy substitution, good film-forming and solubility);

[0355]

[0328] Commercially available Pharmacoat series by Shin-Etsu including Pharmacoat 603 (-3 mPa- s), Pharmacoat 606 (-6 mPa s), Pharmacoat 615 (-15 mPa s);

[0356]

[0329] Commercially available Hypromellose, HPMC by Colorcon / Ashland, including HPMC 2910 3 cP (low viscosity, excellent for thin films), HPMC 2910 6 cP, HPMC 2910 15 cP.

[0330] Polyvinyl alcohol (PVA) comes in many grades that differ in molecular weight and degree of hydrolysis (DH). Low to partially hydrolyzed PVAs (85-89% DH) are readily soluble in cold water. On the other hand, fully hydrolyzed PVAs (98-99% DH) require heating to dissolve (80-90 °C).

[0357]

[0331] Berlow are some examples of water-soluble PVA grades which may be used for the NaF releasing strip according to the present invention:

[0358]

[0332] Commercially available Mowiol or Poval series by Kuraray including Mowiol® 4-88 a low molecular weight, 88% hydrolyzed, cold-water soluble polymer, Mowiol® 5-88, 88% hydrolyzed, water soluble at room temperature, Mowiol® 8-88, medium MW, 88% hydrolyzed, excellent for film-forming, Mowiol® 18-88, higher MW, still cold-water soluble (good mechanical strength).

[0359]

[0333] Commercially available Selvol™ series by Sekisui including Selvol™ 203, 87-89% hydrolyzed, 13,000-23,000 MW, cold-water soluble, Selvol™ 205, 87-89% hydrolyzed, 31,000-50,000 MW, good for flexible films, Selvol™ 523, -88% hydrolyzed, medium MW, fast dissolution in water.

[0360]

[0334] Products by Sigma-Aldrich / Merck including PVA (87-89% hydrolyzed, MW 13,000-23,000), cold-water soluble, PVA (87-89% hydrolyzed, MW 30,000-70,000), stronger films, soluble in water at room temp, PVA 88% Hydrolyzed, MW 85,000-125,000.

[0361]

[0335] CMC (Carboxymethylcellulose sodium, NaCMC) also comes in a wide range of viscosity grades, measured typically as a 2% aqueous solution at 25 °C. The low viscosity CMC grades are usually in the range of 10-100 mPa s (2% solution) are the most preferable polymers for the NaF releasing strip according to the present invention.

[0362]

[0336] Below are some examples:

[0363]

[0337] Commercially available Aquaion™ CMC / Blanose™ CMC by Ashland, including Blanose™ CMC 7LF, -25-50 mPa s (low viscosity), Blanose™ CMC 7MF, -400-500 mPa s (medium, not low), Blanose™ CMC 7M1F PH, 50-100 mPa s, (low viscosity), Blanose™ CMC 9LF, -10-40 mPa s (very low viscosity), CMC 7L2p, 50-200 mPa s (4% sol.) (extra low).

[0364]

[0338] Commercially available Finnfix®, Cekol® (CP Kelco) including Finnfix® 2, -20-40 mPa s (low viscosity), Cekol® 1000, -25-50 mPa s (low viscosity, high purity, often used in pharma / food), Cekol® 2000, higher viscosity (>800 mPa s, not low).

[0365]

[0339] Product of Sigma-Aldrich / Merck including NaCMC, low viscosity with -25 mPa- s (2% sol.), and NaCMC, very low viscosity with -10-30 mPa s.

[0340] A preferable viscosity for the NaF releasing oral strip according to the present invention is NaCMC low viscosity (-20-50 mPa s, 2% solution) which gives good film-forming support alongside PVA and HPMC, fast hydration / erosion in saliva, and avoids excessive gel thickness

[0366]

[0341] that high-viscosity CMC would cause.

[0367] Below is preferable blend of polymers with specific grade choices and a couple of ready-to- use example formulations and processing notes for the NaF releasing oral strip according to the present invention.

[0368]

[0342] A. Fast-eroding / rapid to very rapid release (soft, fast dis solution) -PVA : CMC : HPMC = 40: 40 : 20 (w / w solids)

[0369]

[0343] B. Balanced (good mechanical strength and moderate erosion)- PVA : CMC : HPMC = 60 : 30: 10 (w / w solids)

[0370]

[0344] C. Non sticky, tough / mechanically robust (stronger, slower erosion)- PVA : CMC : HPMC = 70 : 20 : 10 (w / w solids)

[0371]

[0345] For example a preferable non sticky, tough and mechanically robust (stronger, slower erosion) film is achieved from- PVA : HPMC : CMC = 68.2 : 18.2 : 13.6 (w / w solids), wherein PVA (cold-water / partially hydrolyzed, low-medium MW), is Mowiol® 8-88 (-88% DH, medium MW, good film strength and flexibility) or Selvol™ 523 (-88% DH, medium MW); HPMC (low viscosity, fast film-forming), is Methocel® E5 LV or HPMC 2910 6 cP (viscosity - 5-15 mPa s, 2% sol.) and CMC (low viscosity NaCMC), is Blanose™ 9LF or Blanose™ 7LF (-10- 50 mPa s 2% sol.) or CMC 7L2p, 50-200 mPa s (4% sol.) (extra low).

[0372]

[0346] The optional excipients (% of polymeric solids unless stated) which can be combined with the polymers in the NaF releasing oral strip according to the present invention are Plasticizer (glycerol or PEG 400): 15-25% of total polymer solids (start 20%); NaF active: depends on dose per strip, typical loading 0.5-5% w / w of total dry film (adjust to dose); humectant (optional): propylene glycol or sorbitol 2-6% (helps flexibility and moisture control); taste masker / sweetener including xylitol, sucralose, etc., 1-5%; flavoring agent, preservative, surfactant and pH adjusting agents.

[0373]

[0347] Example of formulation per 200 g of solution (23.6 g solid) for 2 % NaF (w / w of the final dry film):

[0374]

[0348] PVA (Mowiol 8-88)- 12 g

[0375]

[0349] HPMC (E5 LV)- 2.4 g

[0376]

[0350] CMC (9LF)- 3.2 g

[0351] Glycerol- 2.8 g

[0377]

[0352] NaF- 0.5 g

[0378]

[0353] Othe ingredients- 2.73 g

[0379]

[0354] Water- 176-180 g (to make 200 g total)

[0380]

[0355] Target total solids in casting solution: 10-15% w / w (preferably 12% w / w).

[0381]

[0356] Example of formulation per 200 g of solution (24.45 g solid) for 5 % NaF (w / w of the final dry film):

[0382]

[0357] PVA (Mowiol 8-88)- 12 g

[0383]

[0358] HPMC (E5 LV)- 2.4 g

[0384]

[0359] CMC (9LF)- 3.2 g

[0385]

[0360] Glycerol- 2.8 g

[0386]

[0361] NaF- 1.33 g

[0387]

[0362] Othe ingredients- 2.73 g

[0388]

[0363] Water- 176-180 g (to make 200 g total)

[0389]

[0364] This solids range in addition to low-viscosity grades give workable viscosities for doctor blade / slot die casting and reasonable drying times without bubbles / cracks for -100 μm final films.

[0390] Example of processing steps

[0391]

[0365] 1. Dissolve PVA in warm water (60-80 °C) with stirring until clear (PVA hydrates slowly).

[0392]

[0366] 2. Cool to -40-50 °C, add glycerol and mix.

[0393]

[0367] 3. Disperse / dissolve HPMC in water (can be added as pre-dispersed cold slurry or sprinkled with high-shear), add slowly to avoid lumps.

[0394]

[0368] 4. Add CMC last (low viscosity grade disperses fast).

[0395]

[0369] 5. Dissolve / disperse NaF in the solution (note NaF solubility and ionic strength effects).

[0396]

[0370] 6. If needed deaerate (vacuum) to remove bubbles.

[0397]

[0371] 7. Cast on release liner with doctor blade / slot die to wet thickness determined by solids: see note below.

[0398]

[0372] 8. Dry at gentle temperatures (30-50 °C) to avoid migration of NaF and to preserve flexibility.

[0399]

[0373] 9. Cut / laminate and package in moisture proof packs.

[0400]

[0374] Wet thickness guidance to achieve -100 μm dry film

[0401]

[0375] Dry mass per m2for a 100 μm dry film (assume film density - 1.2 g / cm3):

[0376] Volume per m2= area (10,000 cm2) x thickness (0.01 cm) = 100 cm3

[0402]

[0377] Mass = 100 cm3x 1.2 g / cm3= 120 g dry film / m2. If the casting solution is 12% solids, to obtain 120 g dry solids: the required solution mass = 120 g 0.12 = 1000 g solution per m2, that’s a wet film mass of 1.0 kg / m2

[0403]

[0378] Volume for 1.0 kg solution ~ 1.0 L (density ~1), so wet thickness ~ 1.0 L / m2= 1 mm (1000

[0404]

[0379] μm).

[0405]

[0380] Thus, a wet film thickness of ~ 1 mm is needed when casting a 12% solids solution to produce a 100 μm dry film.

[0406]

[0381] Adjust solids % and casting wet thickness accordingly: Increasing solids to 15%, wet thickness target will be ~ 0.8 mm. Decreasing solids to 10%, wet thickness target will be 1.2 mm.

[0407]

[0382] 8) Quick recommendations & next steps

[0408]

[0383] Start lab trials with balanced ratio (60:30: 10) and 12% solids, glycerol 20% of polymer solids. Cast wet at ~1.0 mm to target 100 μm dry film.

[0409]

[0384] Check mechanical strength, tack, dissolution / erosion in saliva simulant, NaF content uniformity, and taste. If film is too soft / tacky —> increase PVA fraction or reduce glycerol by 2-5%. If film is too slow to erode —> increase CMC fraction (or increase HPMC fraction in fast-eroding option). If NaF migrates or crystallizes at surface —> reduce drying temperature or include small humectant (sorbitol) and / or adjust plasticizer.

[0410]

[0385] Example of plasticizers (to improve flexibility or reduce brittleness): Glycerol (glycerin), common, humectant, typical: 10-25% of polymer solids (or 1-5% w / w of total film solution); propylene glycol (PPG) (good humectant / plasticizer), 5-15% of polymer solids; polyethylene glycol 400 (PEG 400) (a liquid plasticizer), often used 5-20% of polymer solids; triacetin (glyceryl triacetate) (good for moisture-sensitive films), 2-10%; sorbitol (liquid or liquid sorbitol solution) (plasticizer and humectant), 5-15%. Glycerol and PG are the most common. PEG 400 can increase tack; triacetin gives good mechanical strength but may affect taste.

[0411]

[0386] Example of sweetening agents (taste masking): Xylitol, a sugar alcohol, cariostatic, typical: 1- 10% w / w; sorbitol (sweet and humectant), 1-8%; sucralose, (high-intensity, heat-stable), 0.01- 0.2%; aspartame, (intense sweetener), 0.02-0.1%; stevia (natural, high intensity), 0.01-0.1%; saccharin, 0.01-0.1%.

[0412]

[0387] Example of flavoring agents (mask taste; preferably water-soluble or emulsified types: Peppermint oil / Menthol (mint flavors) often emulsified, 0.01-0.5%; pearmint oil / wintergreen (methyl salicylate), 0.01-0.5%; citrus flavors (lemon, orange) (natural or artificial), 0.05-0.5%; strawberry, cherry, vanilla (water-dispersible flavor powders or emulsion), 0.05-0.5%.

[0388] Example of pH adjusting / buffering agents (stabilize pH, affect taste and ion speciation): Citric acid (a common acidifier and flavor modifier, typical: 0.05-0.5%; sodium citrate (trisodium citrate or disodium citrate), buffer / chelator, useful to adjust pH and control metal ions, 0.05- 1.0% depending on target pH and buffering capacity; sodium bicarbonate, mild buffer and taste modifier (effervescence if reacting), 0.1-0.5%; phosphate buffers (e.g., sodium dihydrogen phosphate / disodium hydrogen phosphate) for tighter pH control (use with regulator limits).

[0413]

[0389] Example of surfactants / solubilizers (reduce surface tension, help disperse hydrophobic flavors): Polysorbate 80 (Tween 80) - a nonionic, common emulsifier for flavors, 0.01-0.5%; polysorbate 20 (Tween 20) for lighter oils / water dispersions, 0.01-0.5%; sodium lauryl sulfate (SLS), strong anionic surfactant; sorbitan esters (Span 20, Span 60), for oil-in-water emulsions in combination with Tweens; lecithin (soy or sunflower, water-dispersible grades), a natural emulsifier.

[0414]

[0390] Example of preservatives (in aqueous solution / storage it requires for microbiological protection): Sodium benzoate, commonly used in acidic systems (pH < 5.5), 0.05-0.2%; potassium sorbate / Sorbic acid, a mild preservative, 0.05-0.2% (effective at lower pH); methylparaben / propylparaben, broad-spectrum, 0.02-0.2% combined; and benzyl alcohol.

[0415]

[0391] Typical usage ranges

[0416]

[0392] Plasticizers: 10-25% of polymer solids; sweeteners: 0.01-10% (intense sweeteners at ppm); flavors: 0.01-0.5% (often 0.05-0.2%); surfactants: 0.01-0.5%; pH adjusters / buffers: 0.05-1%; preservatives: 0.02-0.2%.

[0417] Example 10A

[0418]

[0393] Formulation Composition

[0419]

[0394] Formulation for 100 g of solution (for film casting)

[0420]

[0395] The following table (TABLE 2) provides the percentage composition and exact amounts required for preparing 100 g of polymer solution before casting.

[0421]

[0396] TABLE 2: Formulation for NaF-Releasing Strip (for preparation of 200 g batch solution)

[0422]

[0397] 2. Equipment List

[0423]

[0398] Preparation Equipment:

[0424]

[0399] 1. Magnetic stirrer or overhead mechanical mixer (for polymer solution preparation)

[0425]

[0400] 2. Hot plate with temperature control (to dissolve PVA)

[0426]

[0401] 3. Precision weighing scale (for accurate ingredient measurement)

[0427]

[0402] 4. pH meter (to adjust pH of the solution)

[0428]

[0403] 5. Viscometer (to check solution viscosity, recommended 200-500 cP)

[0429]

[0404] Film casting and drying equipment:

[0430]

[0405] 6. Coating machine / film applicator (e.g., Doctor Blade or Slot Die Coater) (for even film casting)

[0406] 7. Silicone-coated polyester film or Scotchpak (as a backing layer during drying)

[0431]

[0407] 8. Drying oven with controlled temperature and humidity (to ensure uniform drying of strips without degradation of NaF)

[0432]

[0408] Cutting and packaging equipment:

[0433]

[0409] 9. Rotary or Guillotine cutter (to cut dried film into strips of uniform size)

[0434]

[0410] 10. Heat sealer / blister packaging machine (for final packaging in moisture-proof pouches)

[0435]

[0411] 11. Humidity-controlled storage cabinet (to store finished strips before packaging)

[0436]

[0412] 3. Production process

[0437]

[0413] Step 1 : Polymer Solution Preparation

[0438]

[0414] 1. Dissolve PVA:

[0439]

[0415] Heat 40 g of deionized water to 80°C.

[0440]

[0416] Slowly add PVA (6 g) while stirring at 500 RPM. Continue stirring until fully dissolved.

[0441]

[0417] Cool the solution to room temperature (25°C).

[0442]

[0418] 2. Dissolve CMC & HPMC:

[0443]

[0419] In a separate beaker, dissolve CMC and HPMC in 30 g of deionized water under continuous stirring.

[0444]

[0420] Mix at 300 RPM for 20-30 minutes until fully hydrated.

[0445]

[0421] 3. Combine Solutions:

[0446]

[0422] Gradually add the CMC-HPMC solution to the PVA solution while stirring at 400 RPM.

[0447]

[0423] 4. Add Other Ingredients:

[0448]

[0424] Add plasticizers (glycerin, optionally in combination with propylene glycol) and stir for 5 minutes.

[0449]

[0425] Add Polysorbate 80 and sweeteners (sucralose, xylitol) and mix for 5 minutes.

[0450]

[0426] Add sodium fluoride (NaF) and mix for another 10 minutes to ensure even dispersion.

[0451]

[0427] Adjust pH to 6.0-7.0 using citric acid and verify with a pH meter.

[0452]

[0428] 5. Final solution check:

[0453]

[0429] Check viscosity (target: 200-500 cP) using a Brookfield viscometer.

[0454]

[0430] If viscosity is too high, add a small amount of deionized water.

[0455]

[0431] Step 2: Film Casting

[0456]

[0432] 1. Prepare Backing Material :

[0457]

[0433] Lay Scotchpak or silicone-coated polyester film on a flat surface.

[0458]

[0434] 2. Casting Process:

[0435] Pour the polymer solution onto the backing material. The dry film is not sticky, therefore, the solution can be cast directly (without backing layer) on a flat surface of polystyrene (like Petrie dish).

[0459]

[0436] Use a Doctor Blade or Slot Die coater to spread the solution evenly.

[0460]

[0437] Film thickness should be 80-150 microns (μm).

[0461]

[0438] Step 3: Drying the Film

[0462]

[0439] 1. Transfer the coated backing layer to a drying oven.

[0463]

[0440] 2. Set drying conditions:

[0464]

[0441] Temperature: 40-50°C

[0465]

[0442] Humidity: Below 50% RH

[0466]

[0443] Time: 8-12 hours (or until the film is dry to the touch and non-sticky).

[0467]

[0444] 3. Check the dried film for uniformity, flexibility, and smooth texture.

[0468]

[0445] Step 4: Cutting and Packaging

[0469]

[0446] 1. Cut the dried film into strips of desired dimensions (e.g., 2 cm x 5 cm).

[0470]

[0447] 2. Weigh each strip (target: 50-100 mg per strip).

[0471]

[0448] 3. Package strips in individual moisture-proof pouches (e.g., foil blister packs).

[0472]

[0449] 4. Heat-seal packaging to protect from humidity.

[0473]

[0450] 4. Quality Control (QC) Tests

[0474]

[0451] 1. Strip integrity and mechanical testing

[0475]

[0452] Check for uniform thickness, flexibility, and absence of cracks.

[0476]

[0453] 2. NaF Assay (Content Uniformity)

[0477]

[0454] Use an Ion-Selective Electrode (ISE) to measure the fluoride content in randomly selected strips.

[0478]

[0455] 3. NaF Release Test (Dissolution Study)

[0479]

[0456] USP Dissolution Method (Paddle, 50 RPM, pH 6.8 buffer, 37C).

[0480]

[0457] Collect samples at 5, 15, 30, 60 minutes and analyze fluoride concentration using ISE.

[0481]

[0458] 4. Stability Testing

[0482]

[0459] Conduct accelerated stability testing (40C / 75% RH for 3 months).

[0483] Example 10B

[0484]

[0460] Formulation for a 200 g batch solution of the NaF-releasing strip based on pregelatinized starch: This 200 g batch formulation provides a stable, fast-dissolving, and sweetened NaF- releasing strip optimized for dental health applications. Table 3. Formulation for NaF -Releasing Strip (200 g batch solution)

[0485]

[0461] Production Process

[0486]

[0462] 1. Preparation of the Solutions

[0463] 1. Preparation of Polymer Solution (Main solution) Heat deionized water to 70°C and gradually disperse pregelatinized starch (15 g) under moderate stirring (300 rpm). Continue mixing until a uniform gel-like solution forms. Cool to the room temperature.

[0487]

[0464] 2. Dissolution of Sodium Benzoate and Buffering Agent (solution II)

[0488]

[0465] Dissolve sodium benzoate (0.5 g) and sodium citrate (0.26 g) in 10 g of deionized water using a magnetic stirrer at 50°C.

[0489]

[0466] 3. Solution of ZnC12 (Solution III)

[0490]

[0467] In a separate beaker dissolve ZnC12 (2.0 g) in 10 g DW at room temperature using a magnetic stirrer and mix well until a clear solution is obtained.

[0491]

[0468] 4. Solution of SLS, stevia, xylitol and menthol (Solution IV)

[0492]

[0469] In a separate beaker, dissolve SLS (0.5 g) in 10 g of water at room temperature using a magnetic stirrer. Add stevia (0.2 g), xylitol (2 g) and menthol (1 g). Mix for a few minutes for each component to dissolve well.

[0493]

[0470] 5. Addition of Plasticizers

[0494]

[0471] Add sorbitol (4 g) and glycerol (2 g) directly to the main polymer solution and stir for 15 minutes.

[0495]

[0472] 6. Combination of the solutions into the main solution

[0496]

[0473] Add Solutions IV, III and II one after the other in order into the main solution at 200 rpm, while mixing for at least 5 minutes between each addition.

[0497]

[0474] and / or

[0498]

[0475] 4. Incorporation of Active Ingredients

[0499]

[0476] Slowly add sodium fluoride (1.7 g) to the mixture while stirring continuously to ensure uniform dispersion.

[0500]

[0477] 5. Addition of Sweeteners & Flavors

[0501]

[0478] Dissolve xylitol (6 g) and sodium saccharin or stevia extract (0.2 g) in 10 g of warm water and add to the batch.

[0502]

[0479] Add flavoring agents (1 g) and food colorant (if applicable).

[0503]

[0480] 6. Final Mixing & Adjustment

[0504]

[0481] Adjust pH (should be —6-7) with a small amount of sodium citrate if needed.

[0505]

[0482] Add remaining water (approximately 158.2 g total in batch) to achieve 200 g of final solution.

[0506]

[0483] Film Casting and Drying

[0507]

[0484] 1. Casting:

[0508]

[0485] Pour the solution onto a polyester backing layer (e.g., Scotchpak) using a slot-die coater or Dr. Blade.

[0486] Adjust the wet film thickness to achieve a final dry thickness of 100-150 microns.

[0509]

[0487] 2. Drying:

[0510]

[0488] Dry the film in a controlled humidity oven at 40-50°C for 3-5 hours until residual moisture is <10%.

[0511]

[0489] 3. Cutting and Packaging:

[0512]

[0490] Cut into predefined strip dimensions (e.g., 2 cm x 5 cm per strip).

[0513]

[0491] Store in individual foil sachets or sealed plastic containers to prevent moisture absorption.

[0514]

[0492] Target residual water content: 5-10% w / w. This may help to maintain flexibility and prevent brittleness.

[0515]

[0493] The descriptions, drawings, and embodiments set forth herein are provided solely for illustrative purposes and shall not be construed as limiting the scope of the invention or any claims appended hereto. The specific implementation details, features, and operations described in this specification may be combined, separated, or executed in sequences or configurations other than those expressly depicted, and such variations shall not be interpreted as limitations on the invention. The invention is subject to various modifications, substitutions, equivalents, and alternative forms, and may be embodied in forms other than those specifically disclosed, without departing from the spirit and scope of the invention as defined by the appended claims. The terminology used herein is intended solely for descriptive purposes and not for limitation, and all equivalents and variations that fall within the reasonable interpretation of the claims are expressly included. Any references to components, steps, or features being “configured to” perform certain tasks are intended as broad recitations of structure and function and shall not be construed as limiting. The invention may encompass multitasking, parallel processing, and the integration or separation of system components in any suitable form. The scope of the invention shall be determined solely by the reasonable interpretation of the appended claims, and all modifications, substitutions, and combinations that fall within the scope and equivalency of the claims are intended to be encompassed thereby.

Claims

1. CLAIMS1. An adhesive oral film strip for the controlled release of sodium fluoride, comprising: a polymeric matrix consisting essentially of a combination of polyvinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC), and carboxymethylcellulose (CMC); sodium fluoride uniformly dispersed within the polymeric matrix as an active agent; wherein the film strip has a thickness of about 80 to 150 micrometers, and wherein at least one portion of strip comprises said polymeric combination and configured of providing mechanical integrity, controlled erosion in the oral cavity and sustained release of sodium fluoride when applied in situ to the teeth.

2. The strip of claim 1, wherein at least one portion of said strip comprises a member of a group consisting of plasticizer, sweetener or sweetening agent, flavoring agent, surfactant, pH adjusting agent, preservative, and any combination thereof.

3. The strip of claim 1, wherein at least one portion of said strip comprises PVA-CMC- HPMC and said TARP is NaF.

4. The strip of claim 1, wherein the erosible surface further comprises TARP-antitoxic compositions in said at least one second portion of significantly lower TARP content.

5. The strip of claim 1, wherein said TARP is a fluoride-containing substance.

6. The strip of claim 1, wherein said TARP is selected from a group consisting of whitening agent, a desensitizing agent, Remineralization Agents, pH buffer, an antimicrobial agent,7. The strip of claim 1, wherein said antimicrobial agent is selected from a group consisting of Aloe Vera, Amoxicillin, Amoxiclav, Azithromycin, Benzalkonium Chloride, Bergamot Oil (Citrus bergamia), Calcium Hydroxide, Cetylpyridinium Chloride (CPC), Chloramphenicol, Chlorhexidine (CHX), Chloroxylenol, Cinnamon Oil (Cinnamomum verum), Ciprofloxacin, Clindamycin, Clotrimazole, Clove Oil (Syzygium aromaticum), Doxycycline, Dicloxacillin, Essential Oils (e.g., eucalyptol, menthol), Fluconazole, Fluoride including Sodium Fluoride, Stannous Fluoride, fluorapatite (Caio(PO4)6F2) and calcium fluoride (CaF2), Hydrogen Peroxide, Iodine-based antiseptics (e.g., Povidone- lodine), Lactic Acid, Lemon Oil (Citrus limon), Metronidazole, Meropenem, Moxifloxacin, Nystatin, Octenidine Dihydrochloride, Oregano Oil (Origanum vulgare), Peppermint Oil (Mentha piperita), Penicillin, e.g., Penicillin G, Piperacillin-tazobactam, Propolis, Rifampin, Rosemary Oil (Rosmarinus officinalis), Silver Diamine Fluoride,Sodium Hypochlorite, Selenium containing compositions, salts and derivatives thereof, selenious acid selenomethionine selenium-Enriched yeast and extracts thereof, Tetracycline, Tetracyclines (Minocycline, Doxycycline), Tea Tree Oil (Melaleuca altemifolia), Thymus vulgaris, Triclosan (TCS), Ticarcillin-clavulanic acid and any derivatives and combinations thereof.

8. The strip of claim 1, wherein said antimicrobial agent is selected from a group consisting of Hydrogen Peroxide, Carbamide Peroxide, Sodium Perborate, Sodium Bicarbonate (Baking Soda), Calcium Carbonate, Activated Charcoal, Silica, Fluoride-Containing compositions, Bicarbonate Peroxide, Titanium Dioxide, Tetracycline-Modified Dental Materials, Phthalimidoperoxycaproic Acid (PAP), Kaolin, Blue Covarine, Coconut Oil Pulling Agents, Enzyme-Based Whitening Compounds, including Papain, Bromelain, Lysozyme, Amylase, Lipase, Protease, Urease, Cellulase, Aloe Vera Extract, Papain, and Soursop Extract; antibacterial agents that reduce bacterial adhesion on tooth surfaces, including Chlorhexidine, Cetylpyridinium Chloride (CPC), Sodium Fluoride, Triclosan, Essential Oils (such as thymol, eucalyptol, menthol, and methyl salicylate), Tea Tree Oil, Xylitol, Benzalkonium Chloride, Propylene Glycol, Azithromycin, Metronidazole, Lactoferrin, Propolis, Nisin, Aloe Vera; and any derivatives and combinations thereof.

9. The strip of claim 1, wherein said desensitizing agent s selected from a group consisting of Potassium Nitrate, Fluoride, Strontium Chloride, Sodium Fluoride, Amorphous Calcium Phosphate (ACP), Calcium Sodium Phosphosilicate (NovaMin), Tricalcium Phosphate (TCP), Dicalcium Phosphate Dihydrate (DCPD), Arginine, Glutaraldehyde, Resin Ionomer Cements, Desensitizing Agents in Varnishes, Trimetaphosphate (TMP), Hexagonal Hydroxyapatite (HAP), Nickel Titanium, Nickel Chloride, Nickel Oxide, Bioglass (45 S5), S53P4 Bioactive Glass, Sol-gel Derived Bioactive Glass and any derivatives and combinations thereof.

10. The strip of claim 1, wherein said Remineralization Agent is selected from a group consisting of Fluoride, Amorphous Calcium Phosphate (ACP), Calcium Sodium Phosphosilicate (NovaMin), Tricalcium Phosphate (TCP), Dicalcium Phosphate Dihydrate (DCPD), Casein Phosphopeptides (CPP), Nanohydroxyapatite, Xylitol, Recaldent (CPP-ACP), Bioglass, Sodium Bicarbonate (Baking Soda), Sodium Fluoride, Potassium Phosphate, Lactoferrin, Lactate, Green Tea Extract (EGCG), Pectin, Aloe Vera, Collagen Peptides, L-arginine, Seaweed Extracts and any derivatives and combinations thereof.

11. The strip of claim 1 or any of its dependent claims, further comprising a Flavoring and Sensory Enhancement agent, selected from a group consisting of Peppermint Oil, Spearmint Oil, Eucalyptus Oil, Cinnamon Oil, Vanilla Extract, Wintergreen Oil, Clove Oil, Lemon Oil, Strawberry Flavoring, Bubblegum Flavoring, Ginger Root Extract, Honey Flavoring, Apple Flavoring, Peach Flavoring, Orange Flavoring, Grape Flavoring, Mixed Berry Flavoring, Pineapple Flavoring, Watermelon Flavoring, Coconut Flavoring, Anise Oil, Cocoa Flavoring, Sodium Saccharin, Stevia Extract, Citric Acid and any derivatives and combinations thereof.

12. The strip of claim 1, further comprising a pH buffer, selected from a group consisting of Sodium Bicarbonate, Sodium Phosphate, Citric Acid and Sodium Citrate, Potassium Phosphate, Calcium Carbonate, Magnesium Hydroxide, Lactic Acid and Lactate Salts, Trometamol (Tris), Arginine, Amino Acids (e.g., Glycine, Histidine), Boric Acid, Sodium Acetate, Acetic Acid and Sodium Acetate, Sodium Citrate, Alpha-Lactalbumin, Sodium Salts of Fatty Acids, Glycyrrhizin, Ascorbic Acid, Sodium Sulfate, Calcium Phosphate, Potassium Bicarbonate, and Phytic Acid.

13. The strip of claim 1, further comprising surfactant, selected from a group consisting of anti-Fluorosis Agents (including Sodium Fluoride, Stannous Fluoride, Sodium Monofluorophosphate, Calcium Fluoride, Fluoride Varnishes, Amine Fluoride, Fluoridated Silica), Benzalkonium Chloride, Cocamidopropyl Betaine, Cetylpyridinium Chloride (CPC), Colorants, Decyl Glucoside, Glycerin, Glyceryl Monolaurate, Green Tea Extract, Hydroxy ethylcellulose (HEC), Magnesium Aluminum Silicate, Non-Toxic Quaternary Ammonium Compounds (including Benzylalkonium Chloride, Lauralkonium Chloride, Cetyltrimethylammonium Bromide (CTAB)), Polysorbate 20, Polysorbate 80, Quaternary Ammonium Compounds, Sodium Benzoate, Sodium Cocoyl Isethionate, Sodium Dodecyl Sulfate (SDS), Sodium Lauryl Sulfate (SLS), Sodium Saccharin, Sodium Stearoyl Lactylate, Sorbitan Monostearate, Sorbitol, Titanium Dioxide, Xanthan Gum, and Xylitol.

14. The strip of claim 1, further comprising colorants, selected from a group consisting of Alpha-Carotene, Annatto Extract, Beet Juice Powder, Blue 1 (Brilliant Blue), Broccoli Extract, Carotenes (including Beta-Carotene), Carrot Juice Concentrate, Cabbage Color, Chlorophyll, Chlorophyllin, Chia Seed Extract, Elderberry Extract, Food Additives with Color (including Red 40 (Allura Red), Yellow 5 (Tartrazine), Yellow 6 (Sunset Yellow), and Green 3 (Fast Green)), Fruit and Vegetable Extracts (including Blueberry Extract, Strawberry Extract, Spinach Extract, Kale Extract, Red Cabbage Extract, PomegranateExtract, Grape Skin Extract, Raspberry Extract, and Sweet Potato Extract), Hibiscus Extract, Leucopene, Matcha Green Tea Extract, Paprika Extract, Red and Yellow Bell Pepper Extract, Spirulina Extract, Titanium Dioxide, and Turmeric.

14. The strip of claim 1, further comprising a formulation for enhanced drug delivery in dental care comprising at least one member of a group consisting of a. .Amphiphilic Block Copolymers including PEG-PL.A micelles, wherein said micelles encapsulate hydrophobic drugs such as paclitaxel, exemplified by PEG- Polycaprolactone and PEG-PLA for effective drug solubilization; b. Ethosomes utilizing phosphatidylcholine and ethanol in their composition; c. Liposomes formulated to deliver therapeutic agents such as Dexamethasone for inflammation and Amoxicillin as an antibiotic, comprising lipid bilayers made from phosphatidylcholine and cholesterol, particularly employing DSPC and L-a- Phosphatidylethanolamine for drug stability and encapsulation; d. Microemulsions enhancing the solubility of hydrophobic drugs for oral hygiene applications, containing components like Coconut oil, Tween 80, and distilled water for efficient drug solubilization, along with herbal extracts such as ginger for therapeutic effects; e. Nanostructured Lipid Carriers (NLCs) for sustained release of therapeutic agents like chi orhexi dine with compositions of solid lipids like glyceryl monostearate and liquid lipids, improving bioavailability; f. Nanoemulsions encapsulating agents such as eugenol, formulated with Cremophor EL and water for effective penetration and delivery of active ingredients; g. Self-Emulsifying Drug Delivery Systems (SEDDS) comprised of lipids such as Castor oil and surfactants including Kolliphor RH40, capable of enhancing the solubility and bioavailability medicaments; h. Solid Lipid Nanoparticles (SLNs) containing antimicrobial agents such as tea tree oil, utilizing solid lipids like glyceryl monostearate and beeswax for sustained release in the oral cavity; and i. Transferosomes aimed at improving the permeation of therapeutic agents through biological barriers.

17. The strip of claim 4, wherein said TARP-antitoxic composition is selected from a group consisting of methionine and / or vitamin E in Vaseline™; calcium sucrose phosphate; vitamin C; lycopene; mixtures of calcium, vitamin D3, ascorbic acid and antioxidants, and any derivatives and mixtures thereof.

18. The strip of claim 4 or any of its dependent claims, wherein said TARP-antitoxic composition is located closed to the gums and comprises a much lower TARP content then the TARP.

19. The strip of claim 1 or any of its dependent claims, wherein said TARP positioned on at least one of the following: the occlusal, gingival, mesial and lateral side of the teeth.

20. The strip having at least one surface of heterogeneous content of therapeutic agent according to claim 1 or any of its dependent claims, wherein said at least surface comprises at least one first TARP and at least one second portion having a much lower content of a therapeutic agent; said TARP exhibits a sustained release profile of said therapeutic agent over an extended duration.

21. A dental strip for oral care according to claim 1 or any of its dependent claims, comprising an erosible surface, said erosible surface is characterized by that it comprises both (i) at least one first therapeutic-agent rich portion (TARP); and (ii) at least one second portion having a significantly lower TARP content.

22. A biocompatible article of manufacture (BAOM) for oral care having a main plane XY with a main longitudinal axis X:X, perpendicular width of length Y and thickness Z, where X>T»Z; said plane XY having a lateral cross-section and a frontal cross-section; wherein said BP AM comprising at least one erosible surface; wherein the lateral crosssection and frontal cross-section of said erosible surface exhibit portions with varying TARP content; at least one portion is enriched with relatively high TARP content, and at least one portion has a much lower TARP content.

23. The BOAM claim 22, wherein said erosible surface comprises PVA-CMC-HPMC and said TARP is NaF.

24. A multilayered strip of claim 1 or any of its dependent claims, characterized by a flexible or semi-rigid erosible substrate comprising, embedded or otherwise provided in connection with a TARP; and a bioadhesive film layer ensuring prolonged contact with tooth surfaces; said Tarp is selected from one or more members of a group consisting of:a. sodium fluoride or an equivalent thereof concentration in the range of 0.1 - 10% (w:w); b. whitening agent concentration in the range of 0.1 - 50%; c. a desensitizing agent concentration in the range of 0.1 - 10%; d. a remineralization agent concentration in the range of 0.1 - 10%; e. pH buffer concentration in the range of 0.1 - 60%; and f. an antimicrobial agent concentration in the range of 1 - 50%. g. Fluoride from any source at a concentration of 0.05 - 7%.

25. The strip of claim 24, or any of its dependent claims, wherein said erosible surface comprises PVA-CMC-HPMC and said TARP is NaF.

26. The strip of claim 24 or any of its dependent claims, wherein said bioadhesive film used for prolonged contact with tooth surfaces, comprises one or more members of a group consisting of Chitosan Films (including Chitosan-based mouthwash films, Chitosan / gelatin composite films, Chitosan / sodium alginate films, Chitosan -based antimicrobial films), Gelatin Films (including Gelatin-based drug delivery films, Gelatin / Chitosan films, Gelatin / alginate films, Gelatin-based mucoadhesive films), Polyvinyl Alcohol (PVA) Films (including PVA-based oral patches, PVA / Chitosan films, PVA / hyaluronic acid films, PVA / PEG films), Sodium Alginate Films (including Sodium alginate dental gels, Sodium alginate / gelatin films, Sodium alginate / Chitosan films, Sodium alginate-based mucoadhesive films), Polylactic Acid (PLA) Films (including PLA-based bioactive films, PLA / Polyethylene glycol (PEG) films, PLA / chitosan films, PLA with natural extracts), Hyaluronic Acid Films (including Hyaluronic acid-containing dental films, Hyaluronic acid / Chitosan films, Hyaluronic acid / gelatin films, Hyaluronic acid-based mucoadhesive films), Carbopol Films (including Carbopol-based topical gels, Carbopol / polyvinyl pyrrolidone (PVP) films, Carbopol / hyaluronic acid films, Carbopol / Chitosan films), Pectin Films (including Pectin-based oral care films, Pectin with Calcium ions films, Pectin / Gelatin films, Pectin- based drug delivery films), Polycaprolactone (PCL) Films (including PCL-based slow- release films, PCL with hydroxyapatite films, PCL / PLGA (Poly(lactic-co-glycolic acid)) films, PCL-based antimicrobial films), Ethyl Cellulose Films (including Ethyl cellulose matrices in drug delivery systems, Ethyl cellulose / PEG films, Ethyl cellulose / chitosan films, Ethyl cellulose / hydroxypropyl methylcellulose (HPMC) films) and any derivatives and mixtures thereof.

27. The dental strip of claim 1 or any of its dependent claims, comprising a substrate at least partially constructed from polypropylene carbonate).

28. The dental strip of claim 1 or any of its dependent claims comprising an outer layer that provides structural support and adhesion to the teeth, wherein the outer layer is formed from materials selected from the group consisting of polyethylene (PE) film, polypropylene (PP) film, ethylene vinyl acetate (EVA), and hydrocolloid-based adhesives, wherein said materials possess properties of flexibility and strength.

29. The dental strip of claim 1 or any of its dependent claims, wherein the adhesive in the outer layer can be applied using methods selected from the group consisting of spray coating and lamination processes, providing versatility in manufacturing.

30. The dental strip of claim 1 or any of its dependent claims, comprising a supporting layer that is a soft and foamy structure containing fluoride and remineralization agents, providing cushioning and conformability for improved contact with the teeth, wherein the supporting layer is made from materials selected from the group consisting of polyurethane foam, polyvinyl alcohol (PVA) foam, and hydrophilic polyurethane foam.

31. The dental strip of claim 1 or any of its dependent claims, comprising an internal layer that maximizes fluoride delivery and enhances remineralization, wherein the internal layer is made from materials selected from the group consisting of gelatin-based or hydrogel films, chitosan film, and poloxamer gel / film.

32. The strip of claim 1, additionally comprising at least one auxiliary from a group consisting of fixating and immobilizing means, manipulating and administering means, color marks, barcodes, and QR codes, X ray readable markers and any other marker in use in oral care; sensors and indicators, including pH-indicators, time-of-use indicators, expiration-date indicators, sugar-indicators, medicament-indicators, inflammatory- and microbial-indicators, communication means, RFID and any combination thereof.

33. A dental strip kit comprising an erosible dental strip according to claim 1, comprising erosible multiple layers for delivering at least one TARP to teeth and gums, characterized by a lower layer providing structural support and adhesive properties for secure adhesion to teeth; an erosible middle layer that is foamy and soft, facilitating penetration into dental cavities and micro-grooves while carrying fluoride and calcium phosphate to strengthen enamel; and an optionally erosible upper layer containing active therapeutics, further comprising at least two members of a group consisting of sodium fluoride andcasein phosphopeptide-amorphous calcium phosphate (CPP-ACP) for remineralization and decay protection; clear and detailed Instructions for Use (IFU) outlining preparation, placement, recommended duration, post-use guidelines, precautions, warnings, and storage instructions; a specialized application tool for hygienic and accurate application of the dental strip; a durable storage case designed to prevent exposure to moisture, light, and contamination while organizing additional components; an adhesive or retention component to enhance the adherence of the dental strip to teeth; a user-friendly timer for monitoring application duration; a post-treatment product for enhancing the effectiveness of the strip and soothing the oral cavity; a pre-use care product for cleansing teeth of debris to optimize adhesion; and comprehensive safety information detailing potential side effects, contraindications, warnings, and risks to ensure patient awareness and safe usage.

34. A method of manufacturing dental strip of claim 1 or any its depended - claims wherein said strip comprising at least one first erosible substrate, wherein the layers are laminated together using heat or pressure-sensitive adhesives, and wherein fluoride and remineralization agents are applied to the foam or an erosible film layers through spray coating or dip coating methods.

35. A method of Die-Cutting of erosible Strips dental strip of claim 1 or any its depended claims wherein the assembled erosible strips are die-cut into custom shapes that conform to the contours of both the upper and lower teeth to ensure optimal fit and effectiveness during use.

36. A method for delivering fluoride to teeth, comprising of providing an erosible dental strip comprising a flexible substrate; providing the erosible substrate to contain sodium fluoride in a concentration of 1.25% to 5% by weight; applying the strip to the teeth, TARP away from gums, for a treatment period of at least 10 seconds.

37. A method of dental treatment and oral care comprising steps of administering strip as defined in claim 1 or any of its dependent claims on teeth.

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