Oral care kit containing light-emitting element and oral composition

Abstract

The present invention relates to a kit of parts for an oral care device, comprising a light-emitting element and an oral composition comprising curcumin, curcuminoids, curcumin derivatives, or hypericin.

Description

Technical Field

[0001]

[0001] The present invention relates to the field of dental supplies, particularly to kits of parts for oral care appliances.

Background Art

[0002]

[0002] Photodynamic therapy (PDT) was first initiated in the oral cavity in the mid-1980s. Hematoporphyrin has been rapidly replaced as an option for photosensitizers by Photofrin and meta-tetrahydroxyphenylchlorin (mTHPC), and these two have been approved for PDT by multiple health authorities for many years. 5-Aminolevulinic acid (ALA) and some dyes (e.g., toluidine and methylene blue) have also been tested. Several different non-thermal lasers have been used, and in recent years, light-emitting diodes (LEDs) have been tried. The biggest drawback of the common treatment methods is that the patient becomes photosensitive for several weeks after systemic administration of the photosensitizer. The bactericidal effect of PDT has also been tested against dental plaque in the oral cavity, but so far, few clinical studies have been conducted. Instead of mechanical cleaning or antibiotic treatment, PDT can also play a role in dental diseases.

[0003]

[0003] In specialized dental care, specialized oral hygiene is required as maintenance or preoperative, intraoperative, and postoperative prevention. Today, this need is addressed by mechanical instruments, such as rotary instruments using professional tooth polishing powders, the application of air flow, sonic devices, and ultrasonic devices. The drawbacks of this method may be wear that may damage the tooth integrity and soft tissues, difficulty in reaching all areas of the oral cavity, the time and technique required for the application of such methods, and the cost of such developed devices.

[0004]

[0004] Furthermore, chemicals such as chlorhexidine (CHX) are mainly used in postoperative management and therapeutic care. The known side effects of CHX are, in particular, taste disorders, brown deposits on teeth, mucosa, and tongue, and sometimes exfoliation of epithelial cells.

[0005]

[0005] Curcumin is a plant-derived polyphenolic active substance with broad-spectrum antibacterial properties. Curcumin inhibits bacterial growth through its structural characteristics and the generation of antioxidant products. Curcumin can inhibit bacterial pathogenic factors through the bacterial quorum sensing control system, inhibit bacterial biofilm formation, and prevent cell adhesion to host receptors. As a photosensitizer, curcumin acts under blue light irradiation to induce phototoxicity and inhibit bacterial growth. Furthermore, curcumin can exert synergistic antibacterial effects with other antibacterial substances.

[0006]

[0006] Therefore, there remains a medical need for individuals to use such oral hygiene tools as toothbrushes, toothpaste, and interdental instruments. However, these tools are not always used for several reasons, such as time constraints and the required frequency. It is strongly recommended that elderly individuals use such tools for daily care. However, this recommendation is often disregarded because the tools and skills required by the individual or caregiver can be complex.

[0007]

[0007] The use of photo-form electromagnetic radiation for oral antimicrobial treatment is known in the art. For example, WO2020084199 discloses a method for treating biological surfaces using photo-form electromagnetic radiation at two different energy levels. Specifically, biological surfaces are any surfaces that are subjected to biological contamination caused or formed by microorganisms, such as dental infections caused by plaque. This treatment can be used in combination with antimicrobial agents, such as chlorhexidine, to target biofilms for oral disinfection. High-energy and low-energy photons need to be used in combination to successfully inactivate biofilms.

[0008]

[0008] Furthermore, light-emitting toothbrushes are also known, for example, as described in US2016038762 or WO2021000612.

[0009] WO2021034905 discloses a luminescent vibrating toothbrush including a motor-equipped handle and a light source located at the proximal end. The brush head is located at the end of the toothbrush, and a drive shaft transmits kinetic energy from the motor to the brush head. The drive shaft includes an optical waveguide from the light source to the end, containing two layers of optical medium with different refractive indices to enable TIR in the optical waveguide. The brush has a tuft plate with bristles, and the water contact angle of the tuft plate is less than 90°, and it is made of a polymer that is at least partially transparent. The handle and the tuft plate are in electrical contact to constitute a contact sensor, and the motion sensor provides motion data. A computing device processes the motion data and contact data to determine when to activate the light.

[0009]

[0010] However, using daily dental care that rivals professional treatment remains a challenge. Therefore, there is still a need for oral hygiene tools that possess improved characteristics of daily personal dental care, such as requiring less manual dexterity, being quicker, and addressing the entire oral cavity rather than just the tooth surface. [Overview of the Initiative] [Problems that the invention aims to solve]

[0010]

[0011] The object of the present invention is to provide an oral hygiene tool with improved characteristics for daily personal dental care or professional dental care. This object is solved by the subject matter of the present invention. [Means for solving the problem]

[0011]

[0012] According to the present invention, a kit of parts for an oral care device is provided, comprising a light-emitting element and a light-activated substance.

[0013] Further embodiments relate to a kit of parts described herein, wherein the light-emitting element includes a handle, a head, and a light source included in the head.

[0012]

[0014] Further embodiments of the kit of parts described herein relate to a kit of parts in which the head is configured as an angular, oval, or round head, as a tray, or as an occlusal splint.

[0013]

[0015] According to one embodiment of the present invention, the head is configured to emit light in all directions toward the oral cavity. The light output head may include one or more light sources. The light output head may further include a diffuser as needed.

[0014]

[0016] According to one embodiment of the present invention, light can be generated by one or more light-emitting diodes. In some cases, high-intensity light is provided by a light source.

[0017] According to one embodiment of the present invention, the photoactivatable substance may be a liquid or a gel. The photoactivatable substance may also be an antimicrobial compound.

[0015]

[0018] One embodiment of the present invention relates to a method for disinfecting the oral cavity, comprising the steps of applying a photoactivatable substance to the oral cavity and irradiating the oral cavity with light provided by a light-emitting element at a wavelength absorbed by the photoactivatable substance. The light-emitting element may include a handle, a head, and a light source contained in the head.

[0016]

[0019] The head can be configured as an angular, oval, or rounded head, as a tray, or as an occlusal splint, and can be configured as a tray or occlusal splint containing multiple light sources. According to one embodiment of the present invention, the tray or occlusal splint is made of a translucent material. [Brief explanation of the drawing]

[0017] [Figure 1]

[0020] This shows dental equipment equipped with multiple light sources. [Figure 2]

[0021] This shows a dental device equipped with a single light source and a diffuser. [Figure 3]

[0022] Discloses dental supplies similar to a toothbrush. [Figure 4]

[0023] Discloses a dental supply configured as a tray. [Figure 5]

[0024] Figure 5A shows tartar near the gum line and the stained area between teeth. Figure 5B shows tartar near the gum line and the stained area between teeth. [Figure 6]

[0025] Shows the results of the first pilot test. [Figure 7]

[0026] Shows the results of the second pilot test. [Figure 8]

[0027] Shows the results of the third pilot test. [Figure 9-1]

[0028] Shows the results of the fourth pilot test. [Figure 9-2] Same as above.

Mode for Carrying Out the Invention

[0018]

[0029] The present invention provides a kit of parts for an oral care device, the kit of parts including a light emitting element and a substance activatable by light.

[0030] The light emitting element may include a handle (1) and a head (2) configured to emit light (Figs. 1 - 4). In one embodiment, the head includes one, two, five, ten, or a plurality of light sources (3).

[0019]

[0031] In some cases, the head may be covered by a diffuser (4). The diffuser can be made of any material that scatters or disperses light in some way to transmit soft light. The diffuser is used to break up the light and distribute it evenly in the oral cavity.

[0020]

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

[0033] Preferably, 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 light has a wavelength of 550 to 690 nm, more preferably 600 to 680 nm, and even more preferably 625 to 660 nm.

[0021]

[0034] According to one embodiment of the present invention, light-emitting diodes (LEDs) are used as a light source. LEDs are typically available as multiple arrays containing 600 or more individual LEDs with substantial output power.

[0022]

[0035] Light emitters may use blue or ultraviolet LEDs to generate radiation in the 280-550 nm range, or red or infrared LEDs to utilize the 650-1000 nm range. Alternatively, a wide variety of different light emitters may be used to produce various radiation characteristics, such as different wavelengths or frequencies.

[0023]

[0036] While many photosensitizers are used in photodynamic therapy, many are unsuitable when placed orally because the products are highly absorbed through the mucous membranes in the mouth, making it impossible to avoid ingesting even small amounts of photosensitizer. Furthermore, the flavor and color of photosensitizers play a significant role.

[0024]

[0037] The photoactivatable substance may be, for example, a radioactive agent that inactivates oral pathogens such as bacteria.

[0038] The concentration of the photosensitizer is within the range of 1 to 10,000 μg / mL, or 1 to 5,000 μg / mL, or 1 to 2,500 μg / mL, or 1 to 2,000 μg / mL, or 1 to 1,000 μg / mL.

[0025]

[0039] Some photosensitizers derived from natural sources, such as curcumin, curcuminoids, or their derivatives, have been found to be ideal for photodisinfection of the oral cavity. Curcumin possesses anti-inflammatory and antibacterial properties. It has the ability to inhibit the production of inflammatory cytokines and enzymes, which may help reduce inflammation and pain in various tissues, including the gums. Regarding its antibacterial properties, curcumin has the ability to inhibit the growth of various types of bacteria, including those associated with plaque and periodontal disease, which may help reduce the severity of oral infections. Low toxicity, limited side effects, availability, low cost, and a full range of beneficial biological properties are the main advantages of curcumin.

[0026]

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

[0027]

[0041] Some curcumin and its structurally related analogs ("curcuminoids") can be activated by specific wavelengths of light. An example of a curcuminoid is shown in the following chemical structure:

[0028] [ka]

[0029] Here, curcumin is represented by R1=OCH3 and R2=OCH3, demethoxycurcumin by R1=OCH3 and R2=H, and bisdemethoxycurcumin by R1=H and R2=H.

[0030]

[0042] Several studies have shown that curcumin possesses broad-spectrum antibacterial activity and strong physiological activity against both Gram-positive and Gram-negative bacteria. Curcumin absorbs blue light (455–460 nm) in its absorption spectrum of 400–500 nm and can be used as an effective natural photosensitizer to facilitate the success of photodynamic treatments.

[0031]

[0043] Blue light-activated curcumin does not exert its bacteriostatic effect through direct contact with cells, but rather through the auto-oxidation mechanism of curcumin. These effects lead to the production of intermediates, increasing the amount of oxygen free radicals in the cell and thereby destroying cellular integrity. Reactive oxygen species (ROS) have a short half-life, and therefore, contact between the photosensitizer and bacterial cells is important. In fact, the closer the photosensitizer is to the bacterial cell, the greater the likelihood of negative effects of ROS on cellular integrity. When bacterial cells are exposed to light, the photosensitizer absorbs light energy, thereby activating and producing ROS such as hydrogen peroxide, superoxide, and singlet oxygen. Subsequently, ROS oxidize components of the cell membrane, including cholesterol, nitrogen-containing and sulfur-containing amino acid residues in proteins, and guanosine in DNA and RNA, leading to cell death. Compared to Gram-positive bacteria, Gram-negative bacteria exhibit greater resistance to the phototoxicity of curcumin.

[0032]

[0044] Tonon et al. (J. Contemp. Dent. Pract. 2015, 16, 1-6) treated isolated Streptococcus mutans (S. mutans) colonies obtained from pooled plaque samples from caries-affected patients with curcumin and blue light. The cells were irradiated with a blue LED for several seconds. It was shown that curcumin activation with blue LED could photoinactivate the plankton suspension of S. mutans bacteria.

[0033]

[0045] However, oral biofilms are well-structured and organized, making them difficult to penetrate. Physical methods such as mechanical disruption or sonication can physically separate the biofilm matrix, allowing for the penetration of antimicrobial agents. Currently, the separated biofilm matrix is ​​removed with a brush and spit out, but antimicrobial agents are usually not applied due to the reduction of oral biofilm. Toothpaste has limited antimicrobial effects due to the active ingredients it contains, such as fluoride, triclosan, and essential oils. Furthermore, some microorganisms may develop resistance to the active ingredients in toothpaste over time. This can further reduce the effectiveness of the antimicrobial properties of toothpaste over time. Photocatalysis destroys bacteria, viruses, and fungi without damaging human cells or causing antimicrobial resistance. Photocatalysis can be used to disrupt the biofilm structure and then eliminate bacteria in the oral cavity.

[0034]

[0046] Curcumin is a yellow pigment found in the rhizome (turmeric) of the perennial herb *Curcuma longa*. This distinct, deep yellow pigment in turmeric is said to cause teeth to yellow over time. To avoid tooth discoloration, curcumin may be treated to yield transparent, white, and / or colorless curcumin. White curcumin can be obtained by catalytic hydrogenation. Furthermore, curcumin can be made colorless through bleaching using ion exchange resins, enzymatic treatment, or hydrogen peroxide. However, when exposed to light emitted by these devices, curcumin will photobleach and lose its color anyway. This also suggests that sufficient disinfection treatment reduces tooth yellowing.

[0035]

[0047] However, curcumin is fat-soluble, and the main limitation in its use in various applications is its insolubility in aqueous solutions, resulting in low bioavailability. Heating curcumin by boiling it in water for 10 minutes increases its solubility 12-fold. The solubility of curcumin can be significantly improved by its binding with polyvinylpyrrolidone (Front Microbiol. 2018 Jun 15;9:1289). The water solubility of curcumin could be dramatically improved when it was bound with galactose (Yadav et al., Sci Rep. 2020 Aug 26;10(1):14204).

[0036]

[0048] By incorporating a mucosal-adhesion polymer that enhances curcumin's adhesion to biofilms and oral mucosa, contact time and the effectiveness of curcumin against bacteria within the biofilm can be improved.

[0037]

[0049] Polyvinylpyrrolidone (PVP) can adhere to the mucosal surface in the oral cavity, extending the residence time of curcumin in tooth biofilms and mucosal tissues. This prolonged contact can improve the effectiveness of curcumin in targeting oral bacteria within the biofilm. PVP can also function as a stabilizer and solubilizer for curcumin, which is normally poorly soluble in water. PVP helps form a stable dispersion of curcumin, thereby improving its bioavailability in the oral environment. Due to its film-forming properties, PVP can form a protective layer containing curcumin, enabling the sustained release of the active ingredient. This film adheres to the tooth and gingival surface, allowing curcumin to maintain its presence in the areas where it is most needed. PVP is generally compatible with a wide range of ingredients and can be used in combination with other mucosal-adhesion polymers, dissolution accelerators, or biofilm penetration agents, offering diverse options in complex formulations.

[0038]

[0050] It has been found that oral biofilms exhibit good wettability to curcumin, which becomes water-soluble when bound to polyvinylpyrrolidone, e.g., PVP-C. The more important areas of the mouth that satisfy oral hygiene are also those that rapidly absorb this curcumin-PVP-C. Therefore, these critical areas need to be addressed for targeted photodisinfection in the oral cavity. Both curcumin and PVP are already approved as food additives / stabilizers in the EU and US (E100, E1201) and are considered harmless for oral application. Figure 5A shows the areas where curcumin-PVP is primarily absorbed after a short rinse with a composition containing curcumin-PVP (Figure 5A, yellow area) and after rinsing with water (Figure 5B). Curcumin-PVP is absorbed particularly near the gingival margin and in interdental calculus. These areas are typically difficult to target with daily dental hygiene. The combination of curcumin-PVP as a photosensitizer, when used in conjunction with a light-emitting device that activates curcumin-PVP, not only enables highly targeted photodisinfection to areas where it is most needed, but also reduces the adverse effects of phototherapy on the oral mucosa and increased tooth sensitivity.

[0039]

[0051] Activating this photosensitizer requires a very specific LED array of light (wavelength 435±10nm) that minimizes the irradiation time. Furthermore, this shortens the irradiation spectrum to the bare minimum. This shortened time and spectrum significantly reduces the power required for light emission, yet still allows for highly effective disinfection. This further reduces the adverse effects of radiation, thus making it possible to use light to activate photosensitizers in the oral cavity. In fact, the adverse effects of phototherapy on the oral mucosa, especially the gums, are gum pain or inflammation. This can occur if the light source used in the treatment is too strong or the duration of the treatment is too long. The gums may become red, swollen, and painful to the touch, and in severe cases, they may bleed.

[0040]

[0052] Given these specific requirements, intensity, and duration of light needed to activate curcumin and / or curcumin-PVP, an element is required that emits light to areas where plaque biofilm is located in specific locations, namely near the gingival margin and interdental calculus. Indeed, using a light-emitting element as a toothbrush illuminates the areas where the biofilm is located. This is also the area targeted by conventional mechanical removal of plaque.

[0041]

[0053] For example, additional natural photosensitizers such as extracts of Ficus racemosa may be used. The extract can reduce the production of inflammatory molecules in human immune cells and is an anti-inflammatory agent for treating inflammation of the oral mucosa. The antioxidant activity of Ficus racemosa extract may be beneficial for oral mucosa and overall oral hygiene. Chlorophyll-containing compounds, such as toothpaste or mouthwash, are associated with reducing gingival bleeding, plaque buildup, and oral bacterial populations and are effective in reducing bad breath. Phycobiliproteins are natural pigments found in cyanobacteria and certain red algae. Hypericin, found in the plant Hypericum perforatum, is a potent photosensitizer with strong antiviral and antidepressant properties. PDT, particularly its effectiveness in treating skin and organ-specific cancers, has been studied. Phycocyanobilin is found in cyanobacteria, and this pigment is involved in the process of photosynthesis, offering potential for photodynamic applications due to its light-absorbing capacity. Protoporphyrin IX is a naturally occurring porphyrin found in many organisms, playing a role in heme biosynthesis and functioning as an effective photosensitizer. Pheophorbide a is a chlorophyll degradation product. Pheophorbide a has been investigated for its photosensitizing properties in the context of photodynamic therapy. Photosensitizing compounds have been selected from toluidine blue O, methylene blue, dimethylene blue, or azure blue chloride. Psoralens are compounds found in the seeds of watercress (Psoralea corylifolia) and other plants. Psoralens are activated under light exposure and are used in the treatment of skin disorders. Anthraquinones are naturally occurring in plants such as aloe vera and senna. Some anthraquinone derivatives retain photosensitizing properties associated with PDT. Bacteriochlorophyll a can be extracted from photosynthetic bacteria. This chlorophyll derivative absorbs light differently from plant chlorophyll and is useful in low-light environments. Crocetin, the active ingredient in saffron, absorbs light and generates reactive oxygen species, suggesting its potential as a photosensitizer. Bilirubin is primarily a heme degradation product in vertebrates.Bilirubin has been investigated for its photosensitizing properties, particularly in relation to phototherapy for neonatal jaundice.

[0042]

[0054] Within the field of antimicrobial photodynamic therapy (aPDT), photosensitizers such as toluidine blue O and chlorin e6 have been empirically demonstrated to exhibit substantial antimicrobial effects, particularly in the eradication of both single- and multi-biofilms. This established efficacy lays the foundation for investigating alternative photosensitizers that can provide enhanced or equivalent antimicrobial properties. Hypericin possesses unique photodynamic properties and combines them with the advantage of being a natural substance.

[0043]

[0055] The unique combination of hypericin and polyvinylpyrrolidone (PVP) offers a new approach to oral disinfection. This formulation is significantly enhanced by PVP, which leverages the photodynamic properties of hypericin to improve the compound's wettability. Such improvements are crucial to ensure uniform distribution and effective adhesion of the therapeutic compound across diverse surfaces in the oral cavity, including teeth, gums, and mucous membranes.

[0044]

[0056] Hypericin offers comprehensive therapeutic effects, including antioxidant, anti-inflammatory, anticancer, and antibacterial properties. When activated by light, hypericin induces a powerful 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 efficient oral disinfection.

[0045]

[0057] Furthermore, concomitant use with PVP not only enhances the applicability of hypericin to the body but also contributes to a safer and more controlled delivery mechanism within the oral environment, minimizing the risk of irritation or adverse reactions. The inherent nonmutagenicity of this formulation ensures its safety under normal use, with no risk of DNA damage or carcinogenic effects.

[0046]

[0058] Integrating this novel hypericin-PVP formulation into routine oral healthcare practices represents a significant advance in the prevention and treatment of oral infections, providing a powerful, safe, and effective method for disinfecting the mouth. This makes the formulation an invaluable tool in both clinical settings and home care, promising substantial improvements in oral hygiene practices and overall dental hygiene.

[0047]

[0059] This composition may further contain agents suitable for bleaching teeth. Common bleaching compositions may contain peroxide-based materials such as hydrogen peroxide, carbamide peroxide, calcium peroxide, sodium percarbonate, perhydrolurea, and peroxyacetic acid.

[0048]

[0060] This composition may further include, as needed, colorants, fragrances, flavorings, or titanium dioxide.

[0061] This composition may be a liquid, paste, or gel.

[0049]

[0062] The element according to the present invention provides the additional benefit of disinfecting the entire oral cavity. Because it disinfects the entire oral cavity, it can also eliminate bad breath caused by the oral microbiome.

[0063] During operation, a composition containing a photoactivatable substance is applied to the oral cavity, and radiation with desired properties is generated by a light emitter and transmitted not only to the teeth but to the entire oral cavity.

[0050]

[0064] The composition containing the photoactivatable substance is applied to the oral cavity in a similar manner to applying a mouthwash. The composition remains in the mouth, and then a light-emitting element is inserted into the mouth and moved like a toothbrush to illuminate all parts of the oral cavity. The photoactivatable substance is activated by the light, potentially inactivating microorganisms present in the oral cavity. Due to its unique design, the element can reach interdental areas, oral mucosa, and tongue. As a result, the element can reach areas that are very difficult to access with standard mechanical oral hygiene products. This is achieved by the element's additional ability to further distribute light into pores and crevices.

[0051]

[0065] Light-emitting elements, like light bulbs, have the characteristic of emitting light uniformly in all directions around the light source. This can be achieved using multiple light sources (Figure 1) or through a single light source covered by a diffuser (Figure 2). It is important that the light diffuses throughout the area, is highly intense over short distances, and decreases rapidly as it moves away from the light source. This is different from other known products that attempt to deliver light very intensely to a very specific area or point in the mouth via a light beam.

[0052]

[0066] The head of the light-emitting element may also be configured as a tray containing multiple light sources or as an occlusal splint (Figure 4). According to one embodiment of the present invention, the tray or occlusal splint delivers light and, optionally, photoexcitable material to the teeth or dentures.

[0053]

[0067] In summary, the combined use of curcumin and photocatalysis is entirely effective because bacteria cannot develop resistance to photocatalysis over time. method

[0068] We applied a water-soluble curcumin mouthwash and conducted experiments to evaluate its effects on oral hygiene, particularly in terms of tooth and gum staining and biofilm interaction.

[0054]

[0069] Participants rinsed their mouths with Cur-PVP mouthwash containing 1.0 mg / ml of Cur-PVP. Afterward, photographs of their mouths and teeth were taken to observe changes in color and the presence of biofilm on their teeth and gums.

[0055] observation

[0070] Cur-PVP mouthwash resulted in slight yellowing of the teeth. While this effect largely disappears after rinsing with water, it can be unpleasant for the user (see reference).

[0056]

[0071] There was noticeable discoloration of the gums, shifting towards a more reddish hue. After rinsing with water, the effect diminished to a weaker degree, but the gums appeared healthy and natural, and the user may even perceive the effect positively.

[0057]

[0072] The yellowing was particularly strong in areas where biofilm formation was evident. This was interpreted as an effective interaction between Cur-PVP and the biofilm. This is a strong finding, as Cur-PVP is used to reduce bacterial loads during oral healthcare.

[0058] conclusion

[0073] Water-soluble curcumin mouthwash shows promising results by targeting areas where biofilms form, making it crucial for effective oral treatment. Gum discoloration can be considered a weak positive outcome. Temporary tooth yellowing, while not aesthetically ideal, fades significantly after rinsing with water and does not outweigh the benefits of the mouthwash.

[0059] Pilot study

[0074] A pilot study was conducted to investigate the effects of treating supragingival biofilm with curcumin solution followed by LED irradiation.

[0060]

[0075] Curcumin is a photoactive molecule based on a natural extract of turmeric. This product is a curcumin complex (Cur-PVP) conjugated to polyvinylpyrrolidone to improve its solubility. The photosensitizer was supplied by Planta Natural Products (Planta AG, Vienna, Austria). The product was delivered as a yellow powder, with 100 mg of Cur-PVP containing 3.2 mg of curcumin. This powder was dissolved in distilled water to obtain the desired concentration. The product was protected from light until application.

[0061] Experimental setup

[0076] In vitro biofilm formation by six strains commonly found in supragingival biofilms: Candida albicans, strain ATCC32032T; Streptococcus mutans, strain ATCC700610; Streptococcus oralis, strain OMZ 607 SK248; Veillonella dispar, strain ATCC17748T; Fusobacterium nucleatum, strain OMZ598; and Actinomyces oris, strain OMZ745.

[0062]

[0077] For pre-culture, all strains were transferred to blood agar plates (Colombian blood agar, CBA supplemented with 5% defibrous sheep blood). Except for C. albicans cultured at 10% CO2 and 37°C, the blood agar plates were incubated anaerobically at 37°C for 72 hours. After transferring to 0.3% glucose-supplemented FUM medium and incubation overnight, the strains (except for C. albicans cultured at 10% CO2) were stored anaerobically at 37°C for 5 hours in fresh 0.3% glucose-supplemented FUM medium. Using a treated human saliva pool (diluted and sterile KOMI donor pool), 9 mm hydroxyapatite discs (Clarkson Chromatography Products) were prepared at room temperature for at least 4 hours with gentle shaking. Once the pellicle formed, the HA discs were transferred to a 24-well culture dish (Thermo Scientific) containing a mixture of treated saliva and 0.3% glucose-supplemented FUM medium. The mixture was maintained at 37°C for 45 minutes to reduce the medium. The OD of each bacterial suspension was adjusted to 1.0 at 550 nm. After preparing inoculum with the same volume of each bacterial suspension, it was added to reducing medium and incubated under anaerobic conditions at 37°C for 16 hours. Washing was performed three times daily on all disks, replenishing the medium every morning. For the first 16 hours, replenished 0.3% glucose-supplemented FUM medium was used, followed by 24 hours using 0.15% glucose and 0.15% sucrose-supplemented FUM medium. After 40 hours of biofilm growth, the biofilms were washed as described and collected for culture analysis. Colony-forming units (CFUs) were counted under a light microscope.

[0063] Details of the pilot study groups 1-4 1. In vitro efficacy of aPDT using curcumin-PVP against 6 types of biofilm model I.

[0078] Project objective: To evaluate the effectiveness of aPDT using curcumin-PVP on six types of biofilm models.

[0079] Null hypothesis: When curcumin-PVP is treated with aPDT using blue light, there is no difference in total CFU compared to an untreated control. Materials to be tested:

[0080] Untreated control group

[0081] LED control group: 4 LEDs, light for 10 seconds

[0082] 1 minute incubation with 1 mg / ml curcumin

[0083] 1 minute incubation with 0.01 mg / ml curcumin + 4 LEDs, 10 seconds of light exposure

[0084] 1 minute incubation with 0.1 mg / ml curcumin + 4 LEDs, 10 seconds of light exposure

[0085] 1 minute incubation with 1 mg / ml curcumin + 4 LEDs, 10 seconds of light exposure Experimental procedure: Supragingival biofilm, 40 hours, total CFU

[0086] Types of test microorganisms / biofilms treated / intervened: Total CFU, A. oris (OMZ745), V. disper (OMZ493), E. nucleatum (OMZ598), S. mutans (OMZ918), S. oralis (OMZ607), C. albicans (OMZ1134)

[0087] Number of processing groups: 6

[0088] Number of iterations: 1

[0089] Number of implementations: 1 2. In vitro efficacy of aPDT using curcumin-PVP against 6 types of biofilm model II

[0090] Project objective: To evaluate the effectiveness of aPDT using curcumin-PVP on six biofilm models, including the effects of incubation time and washing before light application.

[0091] Null hypothesis: When curcumin-PVP is treated with aPDT using blue light, there is no difference in total CFU compared to treatment with 0.2% CHX. Materials to be tested:

[0092] control group

[0093] LED control group: 4 LEDs, light for 10 seconds

[0094] 3-minute incubation with 1 mg / ml curcumin

[0095] Incubation with 1 mg / ml curcumin for 2 minutes + 4 LEDs, 10 seconds of light exposure.

[0096] Incubation with 1 mg / ml curcumin for 2 minutes + washing + 4 LEDs, 10 seconds of light.

[0097] 3-minute incubation with 1 mg / ml curcumin + 4 LEDs, 10 seconds of light exposure.

[0098] 3-minute incubation with 1 mg / ml curcumin + washing + 10 seconds of light from 4 LEDs

[0099] Apply 0.02% CHXglu for 2 minutes.

[0100] Experimental procedure: Supragingival biofilm, 40 hours, total CFU

[0101] Types of test microorganisms / biofilms treated / intervened: Total CFU, A. oris (OMZ745), V. disper (OMZ493), E. nucleatum (OMZ598), S. mutans (OMZ918), S. oralis (OMZ607), C. albicans (OMZ1134)

[0102] Number of processing groups: 6

[0103] Number of iterations: 1

[0104] Number of implementations: 1 3. In vitro efficacy of aPDT using curcumin-PVP against 6 types of biofilm model III

[0105] Project objective: To evaluate the effectiveness of aPDT using curcumin-PVP on six biofilm models, including the effect of multiple treatment applications during a 40-hour biofilm growth period.

[0064]

[0106] Null hypothesis: When curcumin-PVP is treated with aPDT using blue light, there is no difference in total CFU compared to treatment with 0.2% CHX. Materials to be tested:

[0107] control group

[0108] LED control group: 4 LEDs, 10 seconds of light exposure at 16 and 40 hours.

[0109] LED control group: 4 LEDs, 10 seconds of light exposure at 16 hours, 24 hours, and 40 hours.

[0110] 3-minute incubation with 1 mg / ml curcumin at 16 hours and 40 hours.

[0111] 3-minute incubation with 1 mg / ml curcumin at 16, 24, and 40 hours.

[0112] 3-minute incubation with 1 mg / ml curcumin at 16 and 40 hours + 4 LEDs, 10 seconds of light.

[0113] Incubation with 1 mg / ml curcumin for 3 minutes + washing + 4 LEDs, 10 seconds of light at 16, 24, and 40 hours.

[0114] Application of 0.02% CHXglu for 2 minutes at 16 hours and 40 hours.

[0115] Application of 0.02% CHXglu for 2 minutes at 16 hours, 24 hours, and 40 hours.

[0116] Number of processing groups: 9

[0117] Number of iterations: 1

[0118] Number of implementations: 1 4. In vitro efficacy of aPDT using curcumin-PVP against 6 types of biofilm model III

[0119] Project objective: To evaluate the effectiveness of aPDT using curcumin-PVP against methylene blue on six biofilm models, and to compare the effectiveness of novel light sources.

[0120] Null hypothesis: When curcumin-PVP is used in aPDT with blue light, there is no difference in total CFU compared to methylene blue activated with red light. Materials to be tested:

[0121] control group

[0122] LED control group: 4 LEDs, 2W (440nm) for 10 seconds

[0123] LED control group: 1 LED, 100W (440nm) for 10 seconds

[0124] LED control group: 1 LED, 5W (660nm) for 10 seconds

[0125] 5-minute incubation with 1 mg / ml curcumin

[0126] Incubation with 1 mg / ml methylene blue for 5 minutes.

[0127] 5-minute incubation with 1 mg / ml curcumin + 10 seconds with 4 LEDs at 2W.

[0128] Incubation with 1 mg / ml curcumin for 5 minutes + 1 LED, 100W for 10 seconds

[0129] Incubation with 0.1 mg / ml methylene blue for 5 minutes + 1 LED, 5W (660nm) for 10 seconds

[0130] Number of processing groups: 9

[0131] Number of iterations: 2

[0132] Number of implementations: 1 statistical analysis Data was recorded in a spreadsheet (Microsoft Excel, Microsoft Corporation, Redmond, Washington, USA) and a scatter plot was obtained. Further statistical analysis could not be performed due to the small sample size during the trial phase.

[0065] result

[0133] With the exception of the last pilot study, each point represents a single value. There is no available mean or standard deviation. From other studies using similar methods, it is known that a 1000-fold factor in total CFU usually yields significant results when the study is conducted properly.

[0066]

[0134] As shown in Figure 6, the total CFU (log) is approximately 10 for all cases. 8 It is within this range. In the second pilot test, as shown in Figure 7, the total CFU (log) was approximately 10 7 ~10 9It falls within this range. One of the aPDT groups and chlorhexidine appear to have a strong effect on C. albicans. In the third pilot study, as shown in Figure 8, the total CFU (log) was approximately 10 with both chlorhexidine applications. 4 It falls within this range. Compared to the control group, the two aPDT groups showed a total CFU of 10 1 ~10 2 It can be reduced to this extent. In the fourth pilot test, as shown in Figure 9, the total CFU (log) was approximately 10 with methylene blue application, both with and without photoactivation. 6 ~10 7 It is within the range.

[0067] Consideration

[0135] The current sequence of pilot tests has revealed the following: i) Antibacterial photodynamic therapy using Cur-PVP did not significantly affect total CFU and was able to target specific bacterial strains. Targeted reduction of pathogenic bacteria: Streptococcus mutans (OMZ918), which causes dental caries; Streptococcus oralis (OMZ607), an early colonizing bacterium in plaque formation; and Fusobacterium nucleatum (OMZ598), which contributes to biofilm development.

[0068] ii) Repeated application of this treatment resulted in greater effectiveness. iii) aPDT using chlorhexidine and methylene blue was more effective in reducing total CFU, but had lower selectivity for targeting specific bacterial strains.

[0069] iv) Natural photosensitizers remain neutral when used alone, suggesting a low likelihood of toxicity and side effects. The same applies when blue light is used alone.

[0136] While the mean or standard deviation is not given in the pilot study, a certain level of controls, including negative controls using light only and Cur-PVP only, suggests that the data are robust to some extent. This further suggests that the experimental setup was carefully carried out and that similar results could be obtained if repeated.

[0070]

[0137] The incubation time of Cur-PVP, the concentration of Cur-PVP, pre-treatment washing, and irradiation at various intensities were evaluated across the four pilot studies. Three applications over 40 hours yielded a positive effect.

[0071]

[0138] Another finding was that light alone and Cur-PVP alone had no effect. It still appears that only photoactivation resulted in a reduction in bacteria. This is an important finding for prophylactic use, as side effects are unacceptable in a treatment applied daily. This was not the case when methylene blue was used. aPDT with methylene blue was more effective, but methylene blue alone already had a strong effect on bacterial count.

Claims

1. A kit of parts for oral care devices, a. Light-emitting element, and b. Oral compositions containing curcumin, curcuminoids, curcumin derivatives, or hypericin The above kit of parts includes the above.

2. The kit of parts according to claim 1, wherein the light-emitting element includes a handle, a head, and at least one light source included in the head.

3. The kit of parts according to claim 2, wherein the head is configured as an angular, oval, or round head, as a tray, or as an occlusal splint.

4. The kit of parts according to claim 2, wherein the light output head is configured to emit light in all directions toward the oral cavity.

5. A kit of parts according to any one of claims 1 to 4, wherein the optical output head includes a plurality of light sources.

6. The kit of parts according to any one of claims 1 to 4, wherein the light output head further includes a diffuser.

7. A kit of parts according to any one of claims 1 to 6, wherein light is generated by one or more light-emitting diodes.

8. A kit of parts according to any one of claims 1 to 7, wherein the light source emits blue light.

9. The kit of parts according to claim 8, wherein the blue light has a wavelength in the range of 400 nm to 500 nm.

10. A kit of parts according to any one of claims 1 to 9, wherein the oral composition comprising curcumin, curcuminoids, or derivatives thereof is a liquid, paste, or gel.

11. A kit of parts according to any one of claims 1 to 10, wherein the concentration of curcumin, or curcuminoids, curcumin derivatives, or hypericin is in the range of 0.01 to 10 mg / mL, or 0.05 to 5 mg / mL, or 0.1 to 3 mg / mL.

12. A kit of parts according to any one of claims 1 to 11, wherein curcumin, a curcuminoid, or a curcumin derivative, or hypericin is bound to polyvinylpyrrolidone.

13. The kit of parts according to any one of claims 1 to 12, wherein curcumin, or curcuminoids, or derivatives thereof, are colorless.

14. A method for disinfecting the oral cavity, comprising the steps of: applying a composition containing curcumin, curcuminoids, curcumin derivatives, or hypericin to the oral cavity; and emitting light from a light-emitting device to the oral cavity at a wavelength absorbed by curcumin, curcuminoids, or their derivatives.

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

16. The method according to claim 15, wherein the head is configured as an angular, oval, or round head, as a tray, or as an occlusal splint.

17. The method according to any one of claims 14 to 16, wherein the composition comprising a photoactivatable substance is a liquid or a gel.

18. The method according to claim 17, wherein the photoactivatable substance is an antimicrobial 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 of curcumin, curcuminoid, curcumin derivative, or hypericin is in the range of 0.01 to 10 mg / mL, 0.05 to 5 mg / mL, or 0.1 to 3 mg / mL.

21. The dental hygiene composition according to claim 19 or 20, wherein curcumin, curcuminoid, curcumin derivative, or hypericin is bound to polyvinylpyrrolidone.

22. The dental hygiene composition according to any one of claims 19 to 21, wherein curcumin, curcuminoid, or curcumin derivative is colorless.

23. A dental hygiene composition according to any one of claims 19 to 22, which is a liquid, paste, or gel.

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