Oral care kit comprising light emitting device and oral composition

Abstract

The present invention relates to a kit of parts for an oral care implement, the kit of parts comprising a light emitting device and an oral composition, the oral composition comprising curcumin, curcuminoid, curcumin derivative or hypericin.

Description

Technical Field

[0001] This invention relates to the field of dental devices, and more particularly to complete sets of components for oral care appliances. Background Technology

[0002] Photodynamic therapy (PDT) was first applied to the oral cavity in the mid-1980s. Hematoporphyrin was rapidly replaced by photofrin and mTHPC (meta-tetrahydroxyphenylchlorin) as the preferred photosensitizers, and both have been approved for use in PDT by several health agencies over the years. In addition, 5-aminolevulinic acid (5-ALA) and some dyes (e.g., toluidine and methylene blue) have also been tested. Several different non-thermal lasers have been used, and light-emitting diodes (LEDs) have recently been explored. The biggest drawback of conventional therapy is that patients remain light-sensitive for several weeks after systemic application of the photosensitizer. The bactericidal effects of PDT have also been tested on dental plaque, but clinical application has been limited to date. PDT can also play a role in dental disease as an alternative to mechanical cleaning or antibiotic treatment.

[0003] In professional dentistry, specialized oral hygiene is required for tooth maintenance or as a pre-, intra-, and post-operative preventative measure. This need is now met through mechanical instruments such as rotary instruments for using specialized toothpaste, airflow application mechanisms, sonic devices, and ultrasonic devices. The disadvantages of these methods include: potential abrasions that could damage tooth integrity and soft tissues; difficulty accessing all areas of the oral cavity; the time and skill required to perform these procedures; and the cost of these advanced devices.

[0004] In addition, chemical agents such as chlorhexidine (CHX) have been widely used in surgical and treatment care. Known side effects of CHX include, in particular, taste disturbance; brown staining of teeth, mucous membranes, and tongue; and sometimes epithelial cell desquamation.

[0005] Curcumin is a plant-derived polyphenol with broad-spectrum antibacterial properties. Curcumin inhibits bacterial growth due to its structural characteristics and the production of antioxidant products. It can inhibit bacterial virulence factors, suppress bacterial biofilm formation, and prevent bacterial adhesion to host receptors through the bacterial quorum sensing regulatory system. As a photosensitizer, curcumin functions under blue light irradiation to induce phototoxicity and inhibit bacterial growth. Furthermore, it can exert synergistic antibacterial effects with other antibacterial substances.

[0006] Therefore, there remains a medical need for individuals to use oral hygiene tools such as toothbrushes, toothpaste, and interdental appliances. However, these tools are not used consistently for various reasons, such as time constraints and required frequency. Their use is strongly recommended, especially for older adults, for their daily care. However, this recommendation is often overlooked because individuals or caregivers sometimes require sophisticated tools and skills.

[0007] It is generally known in the art to use electromagnetic radiation, presented as light, for antibacterial therapy of the oral cavity. For example, WO2020084199 discloses a method for treating biological surfaces using electromagnetic radiation presented as light in two different energy levels. Specifically, a biological surface refers to any surface susceptible to biocontamination caused or formed by microorganisms, such as dental infections caused by dental plaque. This therapy can be combined with antibacterial substances such as chlorhexidine to target biofilms for oral disinfection. To successfully inactivate the biofilm, a combination of high-energy and low-energy photons must be employed.

[0008] In addition, toothbrushes capable of emitting light are also known, for example, as disclosed in patent documents US2016038762 or WO2021000612.

[0009] WO2021034905 discloses a light-emitting oscillating toothbrush, comprising a handle with a motor and a light source located at the proximal end. A brush head is located at the distal end of the toothbrush, and a drive shaft transmits kinetic energy from the motor to the brush head. The drive shaft includes a light guide from the light source to the distal end and comprises two layers of optical media with different refractive indices to achieve TIR (total internal reflection) within the light guide. The toothbrush has a tuft plate with bristles made of a polymer, the tuft plate having a water contact angle of less than 90 degrees and being at least partially transparent. The handle and the tuft plate have electrical contacts to form contact sensors, and a motion sensor provides motion data. A computing device processes the motion and contact data to determine when to activate the light.

[0010] However, providing routine dental care comparable to professional treatment remains challenging. Therefore, there is still a need for improved oral hygiene tools for daily personal dental care that require less manual skill, are less time-consuming, and can address issues not only on the tooth surface but also throughout the entire oral cavity. Summary of the Invention

[0011] The object of this invention is to provide oral hygiene tools with improved properties for daily personal or professional dental care. The subject matter of this invention addresses this object.

[0012] According to the present invention, a set of components for an oral care appliance is provided, the set of components including a light-emitting device and a light-activated substance.

[0013] Another embodiment relates to a kit as described herein, wherein the light-emitting device includes a handle, a head, and a light source contained within the head.

[0014] Another embodiment involves a set of components as described herein, wherein the head is configured as an angular head, an oval head, or a rounded head to serve as a dental brace or bite splint.

[0015] According to one embodiment of the invention, the head is configured to emit light into the oral cavity in all directions. The head capable of emitting light may include a single light source or multiple light sources. The head capable of emitting light may optionally also include a diffuser.

[0016] According to one embodiment of the invention, the light may be generated by at least one light-emitting diode. Optionally, high-intensity light may be provided by the light source.

[0017] According to one embodiment of the invention, the photoactivated substance may be a fluid or a gel. Optionally, the photoactivated substance may be an antibacterial compound.

[0018] One embodiment of the present invention relates to a method for disinfecting an oral cavity, the method comprising: applying a photoactivated substance to the oral cavity and irradiating the oral cavity with light provided by a light-emitting device having a wavelength that can be absorbed by the photoactivated substance. The light-emitting device may include a handle, a head, and a light source contained within the head.

[0019] The head is configured as an angular head, an oval head, or a rounded head to serve as a dental tray or bite splint, and the head is configured as a dental tray or bite splint including multiple light sources. According to one embodiment of the invention, the dental tray or bite splint is made of a translucent material. Attached Figure Description

[0020] Figure 1 A dental device with multiple light sources is shown.

[0021] Figure 2 A dental device with a single light source and diffuser is shown.

[0022] Figure 3 A dental device similar to a toothbrush is shown.

[0023] Figure 4 A dental device constructed as a dental tray is shown.

[0024] Figure 5A and Figure 5B The stained areas are shown in the plaque around the gum line and between the teeth.

[0025] Figure 6 The results of the first pilot trial are shown.

[0026] Figure 7 The results of the second pilot trial are shown.

[0027] Figure 8 The results of the third pilot trial are shown.

[0028] Figure 9 The results of the fourth pilot trial are shown. Detailed Implementation Plan

[0029] The present invention provides a set of components for an oral care appliance, wherein the set of components includes a light-emitting device and a photoactivated substance.

[0030] The light-emitting device may include a handle 1 and a head 2 configured to emit light. Figures 1 to 4 In one embodiment, the head includes one, two, five, ten or more light sources.

[0031] Optionally, the head may be covered by a diffuser 4. The diffuser may be made of any material capable of diffusing or scattering light in a certain way to transmit soft light. The diffuser is used to break down the light and distribute it evenly throughout the oral cavity.

[0032] The light source is configured to produce light with a predetermined wavelength and power. The light source includes a light-emitting diode or an array of light-emitting diodes.

[0033] Suitably, the light source is a filtered white light source. Preferably, the light source is a light-emitting diode or an array of light-emitting diodes. Preferably, the wavelength of the light is 550 nm to 690 nm, more preferably 600 nm to 680 nm, and even more preferably 625 nm to 660 nm.

[0034] According to one embodiment of the invention, a light-emitting diode (LED) is used as a light source. LEDs are commercially available as multiplexed arrays, which typically comprise more than 600 individual LEDs and have considerable output power.

[0035] The light emitter can utilize blue or ultraviolet LEDs to generate radiation in the range of 280 nm to 550 nm, or it can use red or infrared LEDs to generate radiation in the range of 650 nm to 1000 nm. Alternatively, a wide variety of different light emitters can be used to provide different radiation characteristics, such as different wavelengths or frequencies.

[0036] Many photosensitizers are used in photodynamic therapy, but many of these are unsuitable when the oral cavity is involved because absorption of the product through the mucous membranes is high in the mouth, and small amounts of photosensitizer ingestion are unavoidable. Furthermore, the taste and color of the photosensitizer play important roles.

[0037] Photoactivated substances can be radiation reactants used to inactivate pathogens such as bacteria in the oral cavity.

[0038] The concentration of the photosensitizer is in the range of 1 µg / mL to 10.000 µg / mL, or in the range of 1 µg / mL to 5.000 µg / mL, or in the range of 1 µg / mL to 2.500 µg / mL, or in the range of 1 µg / mL to 2.000 µg / mL, or in the range of 1 µg / mL to 1.000 µg / mL.

[0039] Several photosensitizers from natural sources, such as curcumin, curcuminoids, or curcumin derivatives, have been identified as ideal for light-based disinfection of the oral cavity. Curcumin possesses anti-inflammatory and antibacterial properties. It has the ability to inhibit the production of pro-inflammatory cytokines and enzymes, and can help reduce inflammation and pain in various tissues, including the gums. Regarding its antibacterial properties, curcumin inhibits the growth of various types of bacteria, including those associated with dental plaque and gum disease, and can help reduce the severity of oral infections. Low toxicity, limited side effects, commercial availability, low cost, and a broad spectrum of beneficial biological properties are among the main advantages of curcumin.

[0040] According to one embodiment of the present invention, the photoactivated substance can be a natural photosensitizer compound, such as curcumin. Curcumin ((1E,6E)-1,7-bis-(4-hydroxy-3-methoxyphenyl)-hept-1,6-diene-3,5-dione) and other curcuminoids constitute the main phytochemicals of the rhizome of *Curcuma longa* L. (Zingiberaceae) (common name: turmeric). Curcumin is a phototoxic photosensitizer and exerts a bactericidal effect on various bacteria under blue light excitation. Furthermore, curcumin can have a synergistic effect with other antibacterial substances in combination therapy to enhance antibacterial properties.

[0041] Curcumin and some of its structurally related analogues (“curcuminoids”) can be activated by light of specific wavelengths. Examples of curcuminoids are shown in the chemical structures below.

[0042] Here, curcumin is represented by R1 = OCH3 and R2 = OCH3. Demethoxycurcumin is represented by R1 = OCH3 and R2 = H, and Didemethoxycurcumin is represented by R1 = H and R2 = H.

[0043] Multiple studies have demonstrated that curcumin possesses broad-spectrum antibacterial activity and exhibits strong bioactivity against both Gram-positive and Gram-negative bacteria. Curcumin absorbs blue light in the 400 nm–500 nm absorption spectrum (455 nm–460 nm) and can be used as an effective natural photosensitizer to promote successful photodynamic treatment.

[0044] Blue light-activated curcumin does not exert its antibacterial effect through direct contact with cells, but rather through its auto-oxidation mechanism. These processes lead to the production of mediators and increase the content of oxygen free radicals in cells, thereby disrupting cell integrity. Reactive oxygen species (ROS) have short half-lives; therefore, contact between the photosensitizer and bacterial cells is crucial. In fact, the closer the photosensitizer is to the bacterial cell, the more likely negative effects of ROS on cell integrity will occur. Once bacterial cells are exposed to light, the photosensitizer absorbs light energy and is activated to produce ROS such as hydrogen peroxide, superoxide, and singlet oxygen. ROS then oxidize cell membrane components including cholesterol, nitrogenous and sulfur-containing amino acid residues in proteins, and guanosine in DNA and RNA, leading to bacterial death. Gram-negative bacteria exhibit stronger resistance to the phototoxicity of curcumin compared to Gram-positive bacteria.

[0045] Tonon et al. (see J. Contem. Dent. Pract. 2015, 16, 1–6) combined curcumin with blue light to treat *S. mutans* (isolated *Streptococcus mutans*) colonies obtained from plaque samples from caries patients. These cells were irradiated with a blue LED device for several seconds. The results showed that activating curcumin with blue LEDs photo-inactivated a suspended suspension of *S. mutans* bacteria.

[0046] However, oral biofilms are well-structured and orderly, making them difficult to penetrate. Physical methods, such as mechanical disruption or sonication, can physically break down the biofilm matrix, allowing antimicrobial agents to penetrate. Currently, the broken biofilm matrix is ​​brushed away and spat out, but antimicrobial agents are typically not applied to reduce oral biofilm. Toothpaste contains active ingredients such as fluoride and essential oils, thus its antimicrobial effect is limited. Furthermore, over time, some microorganisms develop resistance to the active ingredients in toothpaste. This further reduces the effectiveness of toothpaste's antimicrobial properties over time. Photodisinfection can destroy bacteria, viruses, and fungi without harming human cells or inducing antimicrobial resistance. Photodisinfection can be used to disrupt biofilm structures, thereby eliminating bacteria in the oral cavity.

[0047] Curcumin is a yellow pigment found in the rhizome of the perennial herb *Curcuma longa* (turmeric). This dark yellow pigment in turmeric is described as causing teeth to yellow over time. To avoid tooth staining, curcumin can be treated to provide transparent white and / or colorless curcumin. White curcumin can be obtained through catalytic hydrogenation. Alternatively, curcumin can be made transparent by using ion exchange resins, enzyme treatment, or bleaching with hydrogen peroxide to render it colorless. However, regardless of the method, when exposed to light emitted from the device, curcumin will be photobleached and lose its color. This also indicates that the sterilization process is sufficient and reduces yellow stains on teeth.

[0048] Although curcumin is fat-soluble, a major limitation in its use across various applications is its insolubility in aqueous solution, resulting in poor bioavailability. Heating curcumin to boiling water for 10 minutes increases its solubility by 12-fold. The solubility of curcumin can be significantly improved by combining it with polyvinylpyrrolidone (see Front Microbiol. 2018 Jun 15; 9:1289). The water solubility of curcumin can be significantly increased when combined with galactose (see Yadav et al., Sci Rep. 2020 Aug 26; 10(1):14204).

[0049] By incorporating mucosa-adhesive polymers to enhance the adhesion of curcumin to biofilms and oral mucosa, the contact time and effectiveness of curcumin to bacteria within biofilms can be increased.

[0050] Polyvinylpyrrolidone (PVP) can adhere to mucosal surfaces in the oral cavity, potentially increasing the residence time of curcumin on tooth biofilms and mucosal tissues. This prolonged contact enhances the effectiveness of curcumin in targeting oral bacteria within the biofilm. PVP can also be used as a stabilizer and solubilizer for curcumin, which is typically poorly soluble in water. PVP helps form stable dispersions of curcumin, thereby improving its bioavailability in the oral environment. Due to its film-forming properties, PVP can form a protective layer containing curcumin, thereby enabling sustained release of the active ingredient. This film adheres to the surfaces of teeth and gums, maintaining curcumin's presence in areas where it is most needed. PVP is generally compatible with a wide variety of ingredients and can be used in combination with other mucosal adhesion polymers, solubility enhancers, or biofilm permeators, making it a versatile option for complex formulations.

[0051] It has been found that oral biofilms exhibit good wettability against curcumin, which becomes water-soluble through binding with polyvinylpyrrolidone (e.g., with PVP-C). Areas in the oral cavity that are crucial for satisfactory oral hygiene are also those that rapidly absorb this curcumin-PVP-C. Therefore, these key areas need to be targeted photodisinfection sites within the oral cavity. Both curcumin and PVP have been approved as food additives / stabilizers (E100, E1201) in the EU and the US and are considered harmless for oral application. Figure 5A This demonstrates the effect of rapid oral rinsing with a composition containing curcumin-PVP. Figure 5A (yellow area) and after washing with water ( Figure 5BCurcumin-PVP is largely absorbed, particularly around the gum line and in interdental plaque. These areas are often difficult to target with routine dental cleaning. By combining curcumin-PVP as a photosensitizer with a light-emitting device to activate it, photodisinfection can be highly targeted to areas essential for good oral health, while also reducing the negative effects of phototherapy on the oral mucosa and the increased tooth sensitivity.

[0052] Activation of this photosensitizer requires a highly specialized array of LEDs (wavelength 435±10 nm), which minimizes irradiation time. Furthermore, this reduces the irradiation spectrum to a minimum. This reduced time and spectrum allows for a significant decrease in the power required for emitted light while maintaining highly effective disinfection. This further reduces the negative effects of radiation, thus enabling the use of this light to activate photosensitizers in the oral cavity. In fact, the negative effects of phototherapy on the oral mucosa, particularly on the gums, are gingival irritation or inflammation. This gingival irritation or inflammation can occur if the light source used in the therapy is too strong or the treatment duration is too long. The gums may become red, swollen, or tender to the touch, and in severe cases, may even bleed.

[0053] Given the specific requirements for light, intensity, and duration needed to activate curcumin and / or curcumin-PVP, a device is needed that emits light specifically in the areas where dental plaque biofilm is located (i.e., around the gum line and on tartar between teeth). In fact, by using a luminescent device as a toothbrush, the area where the biofilm is located is illuminated. This is also the area targeted by conventional and mechanical plaque removal.

[0054] Additional natural photosensitizers, such as Ficus polyphylla extract, can be used. These extracts can reduce the production of inflammatory molecules in human immune cells and are anti-inflammatory agents used to treat oral mucosal inflammation. The antioxidant activity of Ficus polyphylla extract has potential benefits for oral mucosa and overall oral health. Chlorophyll-containing compounds, such as dental floss or mouthwash, can reduce gingival bleeding, plaque buildup, and the number of oral bacteria, and effectively reduce bad breath. Phycobiliproteins are natural pigments found in cyanobacteria and some red algae. Hypericin, found in St. John's wort (Hypericum perforatum), is a potent photosensitizer with strong antiviral and antidepressant properties. Its efficacy in PDT, particularly in treating skin and organ-specific cancers, has been studied. Phycocyanin, found in cyanobacteria, participates in the photosynthetic process and offers potential for photodynamic applications due to its light absorption capacity. Protoporphyrin IX is a naturally occurring porphyrin found in many organisms, playing a role in heme biosynthesis and serving as a potent photosensitizer. Phosphochlorophyll a is a chlorophyll degradation product. Phosphochlorophyll a has been explored for its photosensitizing properties in photodynamic therapy (PDT) environments. Photosensitizer compounds are selected from toluidine blue O, methylene blue, dimethylene blue, or azure blue chloride. Psoralen is a compound found in the seeds of psoralea and other plants. Psoralen is activated upon exposure to light and has been used to treat skin conditions. Anthraquinones are naturally occurring in plants such as aloe and senna. Some anthraquinone derivatives possess PDT-related photosensitizing properties. Bacterial chlorophyll a can be extracted from photosynthetic bacteria. This chlorophyll derivative absorbs light differently than plant chlorophyll, making it useful in environments with less sunlight. Crocin, the active ingredient in saffron, absorbs light and generates reactive oxygen species, indicating its potential as a photosensitizer. Bilirubin is primarily a product of the breakdown of heme in vertebrates. Its photosensitive properties have been explored, particularly in the application of phototherapy for neonatal jaundice.

[0055] In the field of antimicrobial photodynamic therapy (aPDT), photosensitizers such as toluidine blue O and dihydroporphyrin E6 have been empirically validated for their significant antibacterial efficacy, particularly in eradicating single-species and multi-species biofilms. This established effectiveness lays the foundation for exploring alternative photosensitizers that can provide enhanced or comparable antibacterial properties. Hypericin possesses inherent photodynamic capabilities, coupled with the advantages of being a natural substance.

[0056] The unique combination of hypericin and polyvinylpyrrolidone (PVP) offers an alternative approach to oral cavity disinfection. This formulation leverages the photodynamic properties of hypericin and is significantly enhanced by PVP, which improves the wettability of the compound. This improvement is crucial for ensuring uniform distribution and effective adhesion of the therapeutic compound across various surfaces within the oral cavity, including teeth, gums, and mucosa.

[0057] Hypericin offers comprehensive therapeutic benefits, including antioxidant, anti-inflammatory, anticancer, and antibacterial properties. When activated by light, hypericin induces a potent photodynamic response, effectively targeting and eliminating pathogenic microorganisms without disrupting the delicate ecological balance of the oral cavity. This property makes hypericin-PVP formulations an ideal candidate for non-invasive and highly effective oral disinfection practices.

[0058] Furthermore, the combination with PVP not only enhances the physical application of hypericin but also helps establish a safer and more controlled delivery mechanism in the oral environment, minimizing the risk of irritation or adverse reactions. The inherent non-mutagenic nature of this formulation ensures its safety under normal use, without the risk of DNA damage or carcinogenic effects.

[0059] Incorporating this novel hypericin-PVP formulation into routine oral health procedures represents a significant advancement in the prevention and treatment of oral infections, providing a powerful, safe, and effective method for disinfecting the oral cavity. This makes it a valuable tool in both clinical settings and home care, with the potential to significantly improve oral hygiene habits and overall dental health.

[0060] The composition may also contain agents suitable for bleaching teeth. Common bleaching compositions may include peroxide-based materials such as hydrogen peroxide, carbamide peroxide, calcium peroxide, sodium percarbonate, urea peroxide, and peracetic acid.

[0061] The composition may optionally further comprise dyes, fragrances, flavorings, or titanium dioxide.

[0062] The composition may be a liquid, paste, or gel.

[0063] The device according to the invention provides the additional benefit of overall oral cavity disinfection. Due to the overall disinfection of the oral cavity, halitosis caused by the oral microbiota can also be eliminated.

[0064] During the procedure, a composition containing a photoactivated substance is applied to the oral cavity, and radiation with the desired properties is generated using a light emitter, which is transmitted not only to the teeth but also to the entire oral cavity.

[0065] Similar to mouthwash application, a composition containing a photoactivated substance is applied to the oral cavity. The composition remains in the mouth, and then a light-emitting device is inserted and moved around like a toothbrush to illuminate all areas of the cavity. The photoactivated substance is activated by the light and inactivates any microorganisms that may be present in the oral cavity. Due to its unique design, the device can also reach the interdental areas, oral mucosa, and tongue. Therefore, it can reach areas that are difficult for standard mechanical oral hygiene devices to access. This is achieved through the device's additional ability to further distribute light into small cavities and fissures.

[0066] Similar to a light bulb, a light-emitting device has the property of emitting light uniformly in all directions around the light source. This can be achieved through multiple light sources ( Figure 1 ) or through a single light source covered by a diffuser ( Figure 2 This is achieved through a method that allows light to travel at high intensity over short distances to areas surrounding the light source, and the intensity decreases rapidly as the light moves away from the source. This differs from other known devices that attempt to transmit light in a highly focused manner to very specific areas or points in the oral cavity.

[0067] The head of the light-emitting device can also be constructed as a dental tray or bite splint that includes multiple light sources. Figure 4 According to one embodiment of the invention, a dental tray or occlusal splint provides light and, optionally, a photoactivated substance to the teeth or dentures.

[0068] In conclusion, the combination of curcumin and photodisinfection is particularly effective because bacteria cannot develop resistance to photodisinfection over time.

[0069] Methodology

[0070] Water-soluble curcumin mouthwash was applied and experiments were conducted to assess its effects on oral hygiene, particularly on staining of teeth and gums and biofilm interactions.

[0071] Participants rinsed their mouths with Cur-PVP mouthwash containing 1 mg / ml Cur-PVP.0. Photos of the mouth and teeth were then taken to observe changes in color and biofilm presence on the teeth and gums.

[0072] observe

[0073] Cur-PVP mouthwash causes a slight yellow stain on the teeth. This effect largely disappears after rinsing with water; however, it can be bothersome for users (see below).

[0074] The gums showed noticeable staining, turning a deeper red. After rinsing with water, the effect faded to a negligible level; however, the gum color looked healthy and natural, and the user might experience the effect in a rather positive way.

[0075] Particularly in areas where biofilm formation is more pronounced, the yellow staining is very strong. This is interpreted as an effective interaction between Cur-PVP and the biofilm. This is a strong finding because Cur-PVP is used during oral hygiene to reduce bacterial counts.

[0076] in conclusion

[0077] Water-soluble curcumin mouthwash has shown promising results in targeted areas where biofilms form, which is crucial for effective oral treatment. Gingival staining can be considered a weakly positive result. Temporary yellowing of teeth, while aesthetically undesirable, will largely fade after rinsing with water and will not outweigh the benefits of mouthwash.

[0078] pilot study

[0079] A pilot study was conducted to investigate the effects of treating supragingival biofilm with curcumin solution and subsequent LED radiation.

[0080] Curcumin is a natural extract of turmeric and is a photoactive molecule. This product is a curcumin complex combined with polyvinylpyrrolidone (Cur-PVP) to improve its solubility. The photosensitizer is supplied by Planta Natural Products (Planta AG, Vienna, Austria). The product is delivered as a yellow powder, with 100 mg of Cur-PVP containing 3.2 mg of curcumin. Dissolve the powder in distilled water to obtain the desired concentration. The product should be protected from light until the application time.

[0081] Experimental setup

[0082] Six strains typically found in supragingival biofilms were used to form biofilms in vitro: Candida albicans (ATCC 32032T); Streptococcus mutans (ATCC 700610); Streptococcus oralis (OMZ 607 SK248); Veillonella dispar (ATCC 17748T); Fusobacterium nucleatum (OMZ 598); and Actinomyces oris (OMZ 745).

[0083] For pre-culture, all strains were transferred to blood agar plates (Columbia blood agar, CBA containing 5% defibrinated sheep blood). Except for *Candida albicans* cultured at 37°C with 10% CO2, the blood agar plates were anaerobically cultured at 37°C for 72 hours. After transferring the strains to FUM medium containing 0.3% glucose and culturing overnight, the strains (except *Candida albicans* cultured with 10% CO2) were anaerobically stored at 37°C for 5 hours in fresh FUM medium containing 0.3% glucose. Using treated human saliva pools (diluted pasteurized KOMI donor pools), 9 mm hydroxyapatite discs (Clarkson Chromatography product) were conditioned at room temperature for at least 4 hours with gentle agitation. Once a film formed, the HA discs were transferred to 24-well culture dishes (Thermo Scientific) containing a mixture of treated saliva and FUM medium supplemented with 0.3% glucose. To reduce the medium, the mixture was incubated at 37°C for 45 minutes. The OD of each bacterial suspension was adjusted to 1.0 at 550 nm. Inoculum was prepared using equal volumes of each bacterial suspension and added to reducing medium, then incubated anaerobically at 37°C for 16 hours. All trays were washed three times daily, with medium replenished each morning. For the first 16 hours, supplemented FUM medium containing 0.3% glucose was used, followed by switching to FUM medium containing 0.15% glucose and 0.15% sucrose over the next 24 hours. After 40 hours of biofilm growth, the biofilm was washed as described above and collected for culture analysis. Colony forming units (CFUs) were counted under an optical microscope.

[0084] Detailed grouping of pilot trials 1-4 1. In vitro efficiency of aPDT using curcumin-PVP in six biomembrane models I

[0085] Project Objective: To evaluate the efficiency of aPDT utilizing curcumin-PVP in six biomembrane models.

[0086] Null hypothesis: There was no difference in total CFU when aPDT using curcumin-PVP under blue light was compared with the untreated control group. Materials to be tested:

[0087] No treatment control group;

[0088] LED control group: 4 LEDs lit for 10 seconds;

[0089] Incubate with 1 mg / ml curcumin for 1 minute;

[0090] Incubate with 0.01 mg / ml curcumin for 1 minute + 4 LEDs light up for 10 seconds;

[0091] Incubate with 0.1 mg / ml curcumin for 1 minute + 4 LEDs light up for 10 seconds;

[0092] Incubate with 1 mg / ml curcumin for 1 minute + 4 LEDs light up for 10 seconds.

[0093] Experimental procedure: Supragingival biofilm, 40 hours, CFU total.

[0094] Tested microorganisms / biofilms used for treatment / intervention: CFU total, A. oris (OMZ 745), V. dispar (OMZ 493), F. nucleatum (OMZ 598), S. mutans (OMZ 918), S. oralis (OMZ 607), C. albicans (OMZ 1134)

[0095] Number of treatment groups: 6

[0096] Number of repetitions: 1

[0097] Number of runs: 1 2. In vitro efficiency of aPDT using curcumin-PVP in six biomembrane models II

[0098] Project objective: To evaluate the efficiency of aPDT utilizing curcumin-PVP in six biofilm models, including the effects of culture time and pre-light washing.

[0099] Null hypothesis: There was no difference in total CFU when aPDT using curcumin-PVP under blue light was compared with treatment using 0.2% CHX.

[0100] Materials to be tested:

[0101] Control group;

[0102] LED control group: 4 LEDs lit for 10 seconds;

[0103] Incubate with 1 mg / ml curcumin for 3 minutes;

[0104] Incubate with 1 mg / ml curcumin for 2 minutes + 4 LEDs light up for 10 seconds;

[0105] Incubate with 1 mg / ml curcumin for 2 minutes + wash + 4 LEDs light up for 10 seconds;

[0106] Incubate with 1 mg / ml curcumin for 3 minutes + 4 LEDs light up for 10 seconds;

[0107] Incubate with 1 mg / ml curcumin for 3 minutes + wash + 4 LEDs light up for 10 seconds;

[0108] Apply 0.02% CHXglu over 2 minutes;

[0109] Experimental procedure: supragingival biofilm, 40 hours, CFU total.

[0110] The types of tested microorganisms / biofilms for treatment / intervention were: CFU total, A. Oris (OMZ 745), V. dispar (OMZ 493), F. nucleatum (OMZ 598), S. mutans (OMZ 918), S. oralis (OMZ 607), C. albicans (OMZ 1134).

[0111] Number of treatment groups: 6;

[0112] Number of repetitions: 1;

[0113] Number of runs: 1.

[0114] 3. In vitro efficiency of aPDT using curcumin-PVP in six biomembrane models III

[0115] Project objective: To evaluate the efficiency of aPDT utilizing curcumin-PVP in six biofilm models, including the effects of multiple treatments administered during a 40-hour biofilm growth period.

[0116] Null hypothesis: There was no difference in total CFU when aPDT using curcumin PVP under blue light was compared with treatment using 0.2% CHX.

[0117] Materials to be tested:

[0118] Control group;

[0119] LED control group: 4 LEDs lit for 10 seconds at 16 hours and 40 hours;

[0120] LED control group: 4 LEDs lit up for 10 seconds at 16 hours, 24 hours and 40 hours;

[0121] Incubate with 1 mg / ml curcumin for 3 minutes at 16 and 40 hours;

[0122] Incubate with 1 mg / ml curcumin for 3 minutes at 16, 24 and 40 hours;

[0123] Incubate with 1 mg / ml curcumin for 3 minutes at 16 hours and 40 hours, then light 4 LEDs for 10 seconds each.

[0124] Incubate with 1 mg / ml curcumin for 3 minutes at 16, 24 and 40 hours, then wash and light 4 LEDs for 10 seconds.

[0125] Apply 0.02% CHXglu for 2 minutes at 16 and 40 hours;

[0126] Apply 0.02% CHXglu for 2 minutes at 16, 24, and 40 hours.

[0127] Number of patients in the treatment group: 9;

[0128] Number of repetitions: 1;

[0129] Number of runs: 1.

[0130] 4. In vitro efficiency of aPDT using curcumin-PVP in six biomembrane models III

[0131] Project objective: To evaluate the efficiency of aPDT utilizing curcumin-PVP in six biomembrane models by comparing it with methylene blue, and to compare the efficiency of novel light sources.

[0132] Null hypothesis: When comparing aPDT using curcumin-PVP under blue light with that using methylene blue activated by red light, there is no difference in total CFU.

[0133] Materials to be tested:

[0134] Control group;

[0135] LED control group: 4 2 W (440 nm) LEDs for 10 seconds;

[0136] LED control group: One 100 W (440 nm) LED for 10 seconds;

[0137] LED control group: One 5 W (660 nm) LED for 10 seconds;

[0138] Incubate with 1 mg / ml curcumin for 5 minutes;

[0139] Incubate with 1 mg / ml methylene blue for 5 minutes;

[0140] Incubate with 1 mg / ml curcumin for 5 minutes + 4 2W LEDs for 10 seconds each;

[0141] Incubate with 1 mg / ml curcumin for 5 minutes + 1 100W LED for 10 seconds;

[0142] Incubate with 0.1 mg / ml methylene blue for 5 minutes + 1 5W (660 nm) LED for 10 seconds;

[0143] Number of patients in the treatment group: 9;

[0144] Number of repetitions: 2;

[0145] Number of runs: 1.

[0146] Statistical analysis The data was recorded in spreadsheets (Microsoft Excel, Microsoft Corporation, Redmond, Washington, or USA) and scatter plots were generated. Further statistical analysis was not feasible due to the small sample size during the pilot phase.

[0147] result

[0148] Except for the last pilot test, each point represents a single value. No mean deviation or standard deviation was obtained. From other tests using similar methods, it is known that if the test is started correctly, multiplying the coefficient in the total CFU by 1000 will usually provide a significant result.

[0149] like Figure 6 As shown, the total CFU(log) is all around 10. 8 The range is left and right. For the second pilot trial, such as... Figure 7 As shown, the total CFU(log) is in the range of 10. 7 ~10 9 The range is approximately 100°. It appears that one of the aPDT group and chlorhexidine have a strong effect on *C. albicans*. For the third pilot trial, as... Figure 8 As shown, for both chlorhexidine administrations, the total CFU (log) was 10. 4 The range was approximately 10%. Compared to the control group, both aPDT groups reduced total CFU by 10%. 1 ~10 2 For the fourth pilot trial, such as Figure 9 As shown, the total CFU (log) was 10 for both methylene blue applications, with and without photoactivation. 6 ~10 7 The range to the left and right.

[0150] discuss

[0151] A series of pilot trials have revealed that: i) Antimicrobial photodynamic therapy using Cur-PVP can target specific bacterial strains without significantly affecting total CFU. Targeted and reduced pathogens include: Streptococcus mutans (OMZ 918), responsible for dental caries and cavities; Streptococcus stomatologicus (OMZ 607), an initial transplanting bacterium in the plaque formation process; and Fusobacterium nucleatum (OMZ 598), which contributes to biofilm development. ii) Repeated application of this therapy can lead to a greater effect; iii) Chlorhexidine and aPDT using methylene blue are more effective in reducing total CFU and have lower selectivity when targeting specific bacterial strains; iv) Natural photosensitizers remain neutral when used alone, indicating a lower likelihood of toxicity and side effects. This is also true when blue light is used alone.

[0152] Although these pilot trials did not provide mean or standard deviation, the constant levels of control groups, including negative control groups using only light and only Cur-PVP, indicate that the data are robust to some extent. This further suggests that the experimental setup was carefully constructed and capable of providing similar results upon replication.

[0153] The incubation time of Cur-PVP, the concentration of Cur-PVP, pre-light cleaning, and different irradiation intensities were evaluated in four pilot studies. Three applications within 40 hours resulted in positive effects.

[0154] Another finding was that neither light alone nor Cur-PVP alone had any effect. Nevertheless, it appears that only activation achieved through light leads to bacterial reduction. This is an important finding for preventative applications, as daily-administered therapies cannot tolerate side effects. This is not the case with methylene blue. Although aPDT using methylene blue is more effective, methylene blue alone has already had a strong impact on bacterial counts.

Claims

1. A set of components for oral care appliances, the set of components comprising: a. A light-emitting device; as well as b. An oral composition comprising curcumin, curcuminoids, curcumin derivatives or hypericin.

2. The complete set of components according to claim 1, wherein, The light-emitting device includes: a handle, a head, and at least one light source contained in the head.

3. The complete set of components according to claim 2, wherein, The head is constructed as an angular head, an oval head, or a rounded head to serve as a dental brace or occlusal splint.

4. The complete set of components according to claim 2, wherein, The head, capable of emitting light, is configured to emit light into the oral cavity in all directions.

5. The complete set of components according to any one of claims 1 to 4, wherein, The head, which is capable of emitting light, contains multiple light sources.

6. The complete set of components according to any one of claims 1 to 4, wherein, The head, which is capable of emitting light, also includes a diffuser.

7. The complete set of components according to any one of claims 1 to 6, wherein, The light is generated by at least one light-emitting diode.

8. The complete set of components according to any one of claims 1 to 7, wherein, The light source emits blue light.

9. The complete set of components according to claim 8, wherein, The wavelength of the blue light is in the range of 400 nm to 500 nm.

10. The complete set of components according to any one of claims 1 to 9, wherein, The oral composition comprising curcumin, curcuminoids, or curcumin derivatives is a fluid, paste, or gel.

11. The complete set of components according to any one of claims 1 to 10, wherein, The concentration range of curcumin, curcuminoids, curcumin derivatives or hypericin is 0.01 mg / mL to 10 mg / mL, or 0.05 mg / mL to 5 mg / mL, or 0.1 mg / mL to 3 mg / mL.

12. The complete set of components according to any one of claims 1 to 11, wherein, Curcumin, curcuminoids, curcumin derivatives or hypericin may be used in combination with polyvinylpyrrolidone.

13. The complete set of components according to any one of claims 1 to 12, wherein, Curcumin, curcuminoids, or curcumin derivatives are colorless.

14. A method for disinfecting the oral cavity, the method comprising: A composition comprising curcumin, curcuminoids, curcumin derivatives, or hypericin is applied to the oral cavity, and The oral cavity is illuminated with light provided by a light-emitting device, the light having a wavelength that can be absorbed by curcumin, curcuminoids, or curcumin derivatives.

15. The method according to claim 15, wherein, The light-emitting device includes: a handle, a head, and a light source contained in the head.

16. The method according to claim 15, wherein, The head is constructed as an angular head, an oval head, or a rounded head to serve as a dental brace or occlusal splint.

17. The method according to any one of claims 14 to 16, wherein, The composition containing the photoactivated substance is a fluid or gel.

18. The method according to claim 17, wherein, The photoactivated substance is an antibacterial compound.

19. A dental hygiene composition comprising curcumin, curcuminoids, curcumin derivatives or hypericin.

20. The dental hygiene composition according to claim 19, wherein, The concentration range of curcumin, curcuminoids, curcumin derivatives or hypericin is 0.01 mg / mL to 10 mg / mL, or 0.05 mg / mL to 5 mg / mL, or 0.1 mg / mL to 3 mg / mL.

21. The dental hygiene composition according to claim 19 or 20, wherein, Curcumin, curcuminoids, curcumin derivatives or hypericin may be used in combination with polyvinylpyrrolidone.

22. The dental hygiene composition according to any one of claims 19 to 21, wherein, Curcumin, curcuminoids, or curcumin derivatives are colorless.

23. The dental hygiene composition according to any one of claims 19 to 22, wherein, The composition is a fluid, paste, or gel.

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