Method of treatment of biological surfaces

Abstract

To provide a method for treating a surface by photodynamic therapy.SOLUTION: Biological surfaces are treated with electromagnetic radiations in the form of light of two different energy levels, a first light with photons having most energy in the range of 3.5 eV-2.8 eV and a second light with photons having most energy in the range of 1.24 eV-2.48 eV. The surface of the living body is irradiated with the photons of the first light and the second light at the same time. The use of sensitizers in the topical treatment of infectious diseases is also contemplated. To achieve good tissue penetration. Because two or more different energy photons can target molecules in different regions, it is possible to simultaneously apply antimicrobial treatment to different regions of a pathogen.SELECTED DRAWING: Figure 5

Description

[Technical field]

[0001] The present invention relates to anti-pathogen treatment of biological surfaces. In particular, the present invention relates to the treatment of surfaces by photodynamic therapy. This invention relates to a method of treating a face. [Background technology]

[0002] Microorganisms in biofilms are less susceptible to antimicrobial agents than planktonic bacteria. Mechanisms of film tolerance and resistance include the incorporation of antimicrobials into the biofilm matrix. slow penetration, changes in the microenvironment within the biofilm, different stress responses of bacterial cells, and This involves the formation of a subpopulation of so-called persister cells. Through epigenetic transmission, potential resistance can be easily transferred between different species. It is estimated that nearly 100% of infections are caused by biofilms. The population is affected by the selection of species that are less susceptible to the disease, as more susceptible strains of the disease acquire resistance and the less susceptible species are eliminated. It is also associated with increased drug resistance.

[0003] Common biofilm infections include dental infections caused by dental plaque, Skin infections, urinary tract infections, middle ear infections, endocarditis, and implant- or catheter-related Infectious diseases include:

[0004] Successful antimicrobial treatment of microorganisms in biofilms usually requires treatment of planktonic microorganisms. This requires disinfectants or antibiotics at concentrations up to 100 to 1000 times higher than when For example, one study showed that to kill a single-species biofilm of Clostridium sobrinus, Amine fluoride and chlorhexidine at concentrations 100 times higher than those for planktonic Clostridium sobrinus. Similarly, biofilms of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were effectively To effectively treat them, 1000 times higher concentrations of antibiotics are required than for their planktonic forms. The substance had to be administered.

[0005] Dentists often have to fight antibiotic-resistant bacteria in periodontal and endodontic infections. Chlorhexidine, the most common method used by dentists to treat oral infections, is Resistance to disinfectants such as methadone may be correlated with antibiotic resistance. It is being observed.

[0006] Antibiotics have helped humans fight bacterial infections in the past, but most pathogens It is resistant to most antibiotics and the development of new antibiotics is difficult, This could potentially revert to a pre-antibiotic era.

[0007] Therefore, for example in dentistry, the treatment of dental problems caused by bacterial or yeast biofilms Avoid excessive use of antibiotics to treat periodontal disease, endodontic therapy or localized mucosal infections. Therefore, new antimicrobial strategies are needed. Summary of the Invention

[0008] The object of the present invention is to provide a method for antimicrobial treatment while reducing the risk of pathogen resistance development. The purpose is to provide.

[0009] In particular, it is an object to provide a method for treating a biological surface primarily using light.

[0010] The present invention uses a combination of high-energy and low-energy photons to treat the surface of a living body. Surprisingly, the combination of high-energy photons and low-energy light By using both photons simultaneously on a target area of ​​the surface, the It has been shown to provide excellent biocidal efficacy.

[0011] This is just one possibility, and the scope of the invention is not limited to the following description. However, low-energy photons penetrate deep into the surface of tissues and cause a heating effect. However, high energy photons are believed to have a killing effect on the surface. The collected low-energy photons can reach a temperature of 1.5 to 3.5°C, such as 2.7°C, above 1°C. It exerts a tissue heating effect of up to a depth of about 2 cm. In the affected tissue, oxygen pressure and blood circulation increase, and then cell metabolism becomes more active. It is thought that this may enhance the immune response. High-energy photons have a higher energy level than low-energy photons, which penetrate tissue to a greater depth. Although it is shallower than the sting, it is effective in killing endogenous bacteria.

[0012] In this way, two or more photons can be absorbed simultaneously, propagating the target molecule to a higher energy state. Activation of the same target site by photon upconversion reactions stimulated by can be done.

[0013] In one embodiment, the target area is contacted with a photosensitizer and then the target thus treated is The region is divided into first photons with most of their energy between 1.24 eV and 1.65 eV, and second photons with most of their energy between 1. Exposure to a second photon with most of its energy between 8 eV and 3.5 eV a first photon and a second photon are a majority of total photons irradiated to a target area; Preferably, a method is provided in which the percentage is 90% or more.

[0014] In a further embodiment, a photosensitizer is provided for use in the topical treatment of an infection in a mammal. The photosensitizer is applied to a part of the skin or mucous membrane, and the part is subsequently or simultaneously treated with 2. The first photon has most of its energy between 8 eV and 3.5 eV, and the second photon has most of its energy between 1.24 eV and 1.6 The sample is then exposed to a second photon with most of its energy between 5 eV.

[0015] In one embodiment there is provided a photosensitizer for use in the topical treatment of an infection in a mammal, comprising: The photosensitizer is first applied to a portion of the skin or mucosa, and the area is subsequently or simultaneously treated with Most of the electrons are between 3.17 eV and 2.95 eV and between 1.56 eV and 1.45 eV, respectively. These energy levels range from approximately 390 to 4 Supports wavelengths of 20nm and 795-855nm.

[0016] Further embodiments include tissue, biofilm, saliva, skin, dental plaque, dental surfaces and mucosa. A kit for treating a microbial, viral or fungal infection comprising: and a second light consisting of low-energy photons. The first light and the second light are emitted from an optoelectronic component or device. At least 80% of all light emitted by the laser (high-energy photons and low-energy and at least one photosensitizer that can be activated by at least one photon. Provide a kit.

[0017] More specifically, the invention is characterized by what is stated in the independent claims.

[0018] The advantages of using high-energy and low-energy photons to detect endogenous molecules are considerable. and targeting exogenous molecules to shorten the lifespan of reactive or high-energy oxygen. This results in site-specific therapy of targeted molecules.

[0019] According to the present invention, high energy photons are absorbed by endogenous (intracellular) molecules and produce active singlet acids. At the same time, low-energy photons are used to exogenously (extracellularly) photosensitize the cells. When the active singlet oxygen and active oxygen are absorbed by the agent, active singlet oxygen and active oxygen are generated. Oxygen destroys bacteria and viruses present in tissues, biofilms, saliva, skin, dental plaque, and tooth surfaces. It has the effect of inactivating, killing, or reducing microorganisms such as bacteria and fungi.

[0020] This treatment achieves good tissue penetration. Two or more different energy photons are This allows the antimicrobial treatment of different regions of a pathogen simultaneously, by targeting molecules in different regions of the pathogen. Photons of different energies have different tissue treatment and stimulation effects. The combination of high-energy and low-energy photons can be used to generate photons containing genetic material or other molecules. It is important to understand that bacteria communication is important because it can have a detrimental effect on bacteriophages, which are Light can affect such functions, which are evaluated as quorum sensing. It may also affect the production, formation or activation of communication molecules.

[0021] The high-energy photons are typically produced by species associated with or involved in the oxidative stress response in cells. Thus, they may interfere with the therapeutic application of pathogens. One example of such a species is the flavin group of the peroxidase enzyme.

[0022] High and low energy photons can be used with several types of photosensitizers. Activation can occur by a variety of mechanisms, including heat generation, oxygen radicals, and singlet oxygen. Combining therapeutic approaches that target pathogens through non-specific and fundamentally different mechanisms In one embodiment, a low energy ICG with low photons is used together with high energy photons to target the membrane of pathogens with photohypersensitivity. ICG therapy (ICG works 80% by generating heat and 20-15% by generating singlet oxygen) High-energy photons can be used to activate endogenous porphyrin molecules specific to bacteria. Such molecules have high quantum yields and act primarily via singlet oxygen, creating localized oxidative barriers. This causes a stir.

[0023] Endogenous antimicrobial therapy, in which photons target specific bacterial molecules, and exogenous photodynamic therapy, or photothermal therapy. One important advantage of combining the two is that the added exogenous photosensitizer is targeted during treatment. This solves the problem of the color fading easily occurring at the target site.

[0024] However, endogenous antimicrobial phototherapy is not limited to the presence of exogenous photosensitizers. .

[0025] By targeting endogenous molecules specific to bacteria with photons, the attachment and uptake of photosensitizers is relied upon. This allows the photosensitizer to be distributed to areas with low levels of photosensitizer. Treatment can be balanced to provide equal therapeutic benefit to the affected area. The photobleaching effect of endogenous antimicrobial therapy on endogenous molecules of the serovar T cells is different from that of added exogenous photosensitizers. Since these molecules are essential for pathogens, they also have anti-pathogenic functions.

[0026] In the long term, the effectiveness of exogenous treatments is limited to the extent that the photosensitizer is attached to or ingested by the target pathogen. Therefore, by targeting bacteria endogenously and exogenously, in v Best results are achieved with ivo.

[0027] For example, simultaneous absorption of 1.53 eV and 3.06 eV photons results in the formation of endogenous porphyrins. The high-energy photons excite the biofilms, providing antibacterial effects in addition to tissue healing. Reduces the formation of extracellular polysaccharide matrix in the cytoplasm, resulting in synergistic effects with exogenous PDT. , reducing the pathogenicity of biofilms.

[0028] Biopsy at different times using different photosensitizers, photon energies and treatment parameters The film can be targeted at different parts of its life cycle, e.g., dental plaque and The composition of the biofilm and the surface layer of the tooth are different for each individual. Compared with people with a high prevalence of malaria, they had a different bacterial load in the plaque, especially in the early stages of plaque formation. The species and different phylogenetic diversity are shown.

[0029] The present invention allows for the effective treatment of people with high or low caries prevalence. Cut.

[0030] The therapeutic method of the present invention can also be used to treat other biological materials than those having a biological surface. Examples include equipment and equipment parts that are covered with biofilm. Sulfur fouling, also known as sulfur fouling, is a common cause of sulphuric acid fouling in industrial water systems, medical and pulp and paper industries. They may be found in process industries, including food processing, as well as in the food industry.

[0031] The following embodiments will be considered in more detail with reference to the accompanying drawings. [Brief description of the drawings]

[0032] [Figure 1] Photographs showing the specificity of stained dental plaque observed under room light using a Hamamatsu 1394 and a NIR light source. [Diagram 2] FIG. 2 is a diagram illustrating the variation of grey levels showing the light absorption of a dye. [Diagram 3] 1 is a bar graph showing the antimicrobial effect of chlorhexidine enhanced with dual wavelength PDT according to one embodiment of the present invention. [Figure 4] 1 is a bar graph showing the antibacterial effect of PDT treatment on mutans streptococcus biofilms on days 1, 2 and 4. [Diagram 5] 1 is a bar graph showing the efficacy of dual wavelength and single wavelength treatments on day 4 biofilms. [Figure 6] 1 is a graph showing the antibacterial effect of light with a wavelength of 405 nm compared to PDT. [Figure 7] 1 is a bar graph showing the antibacterial effect of PDT treatment on mutans streptococcus biofilms after 14 days. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0033] (definition) In this context, "photodynamic therapy," also known by the abbreviation "PDT," refers to the application of light in some form The term "treatment" refers to any treatment that converts active oxygen into a form of oxygen.

[0034] Examples of "active oxygen" include singlet oxygen, oxygen radicals, and oxygen ions.

[0035] "Antibacterial photodynamic therapy," also known as "aPDT," uses photons to stimulate the " and imparts antimicrobial efficacy in an activated state.

[0036] In one embodiment, "antimicrobial photodynamic therapy" refers to "antibacterial photodynamic therapy."

[0037] In one embodiment, "antibacterial photodynamic therapy" refers to "antifungal photodynamic therapy."

[0038] In one embodiment, "antimicrobial photodynamic therapy" refers to "antiviral photodynamic therapy."

[0039] A "beneficial agent" is generally a chemical compound or compound that has a beneficial effect on a tissue or therapeutic effect. is a substance. Examples of such compounds include: host defense peptides , enzymes, hydrogen peroxide-producing enzymes, specific pH solutions, acids, bases, antibacterial enzymes, honey, hydrogen peroxide, wood Fat, Trolox, EDTA, D-vitamin, antigens, hormones, prolactin, hygroscopic substances Calcium carbonate, alpha-tocopherol, verapamil, sodium bicarbonate, sodium chlorite, pomegranate , aloe vera, chamomile, curcumin, aqua cumin, baking soda, sea salt, turmeric, activated charcoal, Lemon juice, coconut oil pulling, peppermint oil, spearmint oil, Namon oil, DMSO, titanium dioxide, calcium carbonate, carrageenan, lauryl sulfate Sodium, Sodium Monofluorophosphate, Benzyl Alcohol, Peppermint le, parsley oil, sodium benzoate, bromelain, papain, maltodextrin , Citric Acid, Limonene, Silica, Peppermint Extract, Glycerin, Nettle Extract, Bicarbonate.

[0040] "Antibacterial blue light" is also known as "aBL" and is usually 400nm to 470nm. For example, wavelengths of 400 nm to 430 nm, 405 to 470 nm, or 405 to 430 nm This refers to light in the range that exhibits intrinsic antibacterial activity without the involvement of exogenous photosensitizers.

[0041] "Photosensitizer" refers to a substance that absorbs electromagnetic radiation, e.g., in the ultraviolet or visible range, and converts it into an adjacent Photosensitizers are compounds or molecules that can transfer light to molecules that are localized to the target site. It has a π system that is quantized.

[0042] Although the term "photosensitizer" is often used in the singular in this context, this term It also includes a plurality of compounds or molecules. In particular, it is a mixture of two or more photosensitizer compounds or molecules. or sequential use. When multiple photosensitizer compounds or molecules are used, at least one are suitable for use with high-energy photons, and at least one is suitable for use with low-energy photons Suitable for.

[0043] In one embodiment, a selected photosensitizer, in combination with the corresponding light, stimulates endogenous antibodies. It can achieve antibacterial action, and in combination with the corresponding light, it can achieve exogenous antibacterial action. A photosensitizer capable of

[0044] Photosensitizers can be naturally occurring compounds ("natural photosensitizers") and synthetic compounds. Examples of natural photosensitizers include: hypericin, curcumin, phenacylcholine, lenone derivatives, cercosporins, psoralens, xanthotoxins, angelicins, α-tert-butylamines, Thienyl, phenyltetrahydrocannabinol, THC, cannabidiol (CBD). Synthetic photosensitizers These include: RB (Rose Bengal), MB, porphyrin derivatives, Lucumin derivatives, methylene blue, indocinine green, erythrocin, phenalenone derivatives Conductors, fullerene derivatives, xanthene derivatives, resveratrol.

[0045] Other photosensitizers include polyphenol compounds and / or anthocyanin compounds. Representative examples include extracts of berries such as lingonberries and blueberries, which contain

[0046] The term "potentiator or agent" refers to an agent that enhances the effect or activity of another agent or agents. and their combined effect is greater than the sum of their individual effects. It means a drug.

[0047] Examples of "enhancing substances or agents" include ions, ion scavengers, surfactants, oxygen-containing compounds, active oxygen generating compounds, organic and inorganic salts, divalent ions, pigments, antimicrobial peptides, ED These include, but are not limited to, TA, immunostimulants, and antibiotics or chlorhexidine. Other antibacterial compounds that may be used include:

[0048] "Exogenous" when used in reference to a bacterium means "outside" the bacterium.

[0049] "Endogenous" means "intrinsically occurring" in the bacterium. When used in the context, "endogenous" is used interchangeably with the term "intracellular."

[0050] In this context, "mammal" has its conventional meaning in the art. The subjects include humans, dogs, cats, rabbits, horses, cows, sheep, goats, and pigs. , animals kept for farming and as pets.

[0051] "Incoherent" as used in relation to light means that the amplitude and phase of the emitted light waves are In one embodiment, the non-coherent light is In another embodiment, the incoherent light source is a U Including using VC lamps.

[0052] "High energy photons" refers to photons with energy between 3.5 eV and 2.8 eV, particularly between about 3.2 and 2.9 eV or These are photons with energies in the range of 3.17 to 2.95 eV. The photons are about 350 to 450 nm, for example about 380 to 430 nm, for example about 390 to 410 It is contained in light having wavelengths in the nm range.

[0053] "Low energy photons" are those with an energy of 1.24 eV to 2.48 eV, especially 1.3 eV to 2.4 eV. V, for example, an energy range of 1.4 eV to 1.6 eV or 1.45 eV to 1.56 eV Typically, such photons have wavelengths of about 500-1000 nm, e.g., about It is included in light with a wavelength in the range of 780 to 830 nm.

[0054] Light with photons that have "most of their energy in the range of 3.5 eV to 2.8 eV" is, for example, For example, light in the form of a light beam or ray, at least 50%, in particular at least 60%, of the photons At least 70%, at least 80%, at least 90%, or at least 95% of As shown by these energies, 3.5 eV to 2.8 eV or 3.2 eV to 2 It means light with an energy in the range of 0.9 eV, for example 3.17 eV to 2.95 eV.

[0055] What is light produced by photons with most of their energy in the range of 1.24 eV to 2.48 eV? For example, in the form of a light beam or ray, at least 50%, in particular at least 60% or At least 70% or at least 80% or at least 90% or at least 95% , as indicated by their energies (or wavelengths), 1.24 eV to 2.48 eV Or 1.3 eV to 2.4 eV, for example 1.4 eV to 1.6 eV or 1.45 eV to 1 It refers to light with an energy in the range of .56 eV.

[0056] Generally speaking, irradiation with both high and low energy photons, especially simultaneously When irradiated with a low-energy photon-activated photosensitizer, either photon group can be separately It has been found that the antibacterial effect of light is enhanced when compared to when light is irradiated directly onto the floating bacteria. This is also seen in microorganisms, especially biofilms, when irradiated with a single dose.

[0057] Furthermore, this combination, also known as "dual light therapy," can be used long-term as a daily treatment. The ability of the drug to maintain its antibacterial effect on biofilms when used for extended irradiation We know that.

[0058] Treatment using low-energy photons in conjunction with an exogenous photosensitizer, as used in dentistry However, over time, these resistance forms tend to lose their effectiveness against biofilms. There are various reasons for this formation, including activation of genes involved in the expression of influx pumps. Regardless of the cause, or combination of different explanations, in biofilm research in the context of the present invention, When they continued irradiating the cells with high-energy photons every day, they encountered a similar phenomenon.

[0059] Improved efficacy of dual-beam phototherapy as a single dose and treatment that maintains efficacy The ability of the compound to simultaneously generate radical oxygen species by light in the presence of endogenous and exogenous sensitizers was demonstrated. Endogenous sensitizers are photoreactive molecules present inside cells. These molecules include, for example, proteins containing amino acid side chains or saccharides such as flavins and hemes. It may be a protein bound to a chromophore prosthetic group.

[0060] In one embodiment, the chromophore-binding protein is involved in a variety of reactions, such as electron transport reactions in mitochondria. , which plays an important role in cellular function and whose oxidation can have adverse effects.

[0061] Damage to side chain-containing proteins may have a major impact on bystander injury On the other hand, exogenous sensitizers damage both the cell membrane and cell wall structures and, upon entering the cell, It has the ability to achieve rapid and efficient production of radical oxygen species that can damage other structures. Targets of reactive oxygen species on the body surface include DNA, RNA, proteins, lipids, and sterols. Some examples include:

[0062] In the first embodiment, the present technology has most of the energy in the range of 3.5 eV to 2.8 eV. The first light is a photon with most of its energy in the range of 1.24 eV to 2.48 eV. It is electromagnetic radiation in the form of light with two different energy levels, with the second light being a photon with A method of treating a biological surface is provided. The treatment comprises simultaneously delivering first and second light photons to the biological surface. This is done by irradiating the surface.

[0063] As mentioned above, the term majority energy generally refers to 50% of the energy of light. More than, especially more than 60%, e.g., more than 70% or more than 80% is in the indicated range. .

[0064] In one embodiment, the photons have at least 50% of their energy at 3.1 In one embodiment, the photons range from 7 eV to 2.95 eV and from 1.56 eV to 1.45 eV. , and at least 50% of their energy is at about 390-420 nm and 795 nm, respectively. It has a range corresponding to wavelengths of ~855nm.

[0065] In a preferred embodiment, the light used is incoherent.

[0066] In one embodiment, The incoherent radiation energy is then distributed to at least two of the first and second energy levels. at different energy levels; From incoherent synchrotron radiation energy to most of the energy in the first energy level A first light having a corresponding wavelength and a second light having a corresponding majority energy of the second energy level. and a second light having a wavelength; The first light and the second light are simultaneously irradiated onto the surface of the living body.

[0067] In one embodiment, the light comprises a first light of high energy photons and a second light of low energy photons. a second light is generated by using an optoelectronic component and a device thereof capable of simultaneously emitting a second light that is a The first light and the second light are at least one of the total light emitted from an optoelectronic component or device. Both are equivalent to 80%.

[0068] The intrinsic and extrinsic excitation of the biological material on the surface by the above-mentioned light is preferably active singlet. This is accomplished so that free oxygen or reactive oxygen species or both are generated.

[0069] The treatment method can be used to remove surface biological material, such as biological tissue contamination with microorganisms, viruses, or fungi. This treatment can be used for cosmetic purposes as well as for antibacterial and antiviral purposes. It can also be used for viral and antifungal treatment.

[0070] Light can be used as is, or photosensitizers (photosensitizers) can be used for the purpose of photodynamic therapy (PDT). These may also be used in combination with other anti-inflammatory agents, as described in more detail below.

[0071] In one embodiment, the high energy photons and the low energy photons are activated with the low energy photons. The radiation is administered in combination with at least one exogenous photosensitizer that can be activated.

[0072] In one embodiment, a photosensitizer (photosensitizer) for use in the localized treatment of mammalian tissue. applying said sensitizer to a surface site of tissue, such as the skin or mucosa of a mammal; The treated area was then exposed to two different wavelengths of light (i.e., 2.8 eV - The first light is generated by high-energy photons with most of their energy between 3.5 eV and 1.24 eV. (secondary light produced by low-energy photons with most of their energy between 1.65 eV and 1.65 eV) Expose.

[0073] In such an embodiment, the high energy photons are absorbed by endogenous (intracellular) molecules (2. Photon energies of 48 eV or more are activated by porphyrins and riboflavin, etc. At the same time, low-energy photons are exogenously (extracellularly) photoinduced photoproduction. When absorbed by sensitizers, active singlet oxygen and reactive oxygen species are generated. The generated reactive singlet oxygen and reactive oxygen species are distributed in tissues, biofilms, saliva, skin, dental plaque, and Inactivates and kills microorganisms such as bacteria, viruses and fungi present on the surfaces of teeth and mucous membranes. Or they can be lowered.

[0074] In one embodiment of the present invention, the high energy photons are directed to a flavin group, such as a peroxidase enzyme. which are absorbed by intracellular oxidative stress response mechanisms and therefore therapeutic adaptations of pathogens to disrupt.

[0075] In another embodiment, the at least one photosensitizer is administered to tissue, biofilm, saliva, skin, or tissue samples. , microorganisms such as bacteria, viruses and fungi present on targets such as plaque and the tooth surface and mucous membranes. The target is contacted with the photosensitizer by applying it to the target using a carrier. (number) are aqueous solutions, alcohol-containing solutions, hydrophilic gels, hydrophobic gels, hydrophilic polymers, hydrophobic or in the form of a paste, lotion, tablet, tape, salve or band-aid. It can be applied with.

[0076] High-energy and low-energy photons penetrate microorganisms or tissues, biofilms, saliva, etc. It is believed that the IL-10 receptors penetrate to different depths into the skin, dental plaque, tooth surface and mucosa. This technology allows reactive oxygen species and reactive oxygen monolayers to be isolated from tissues, biofilms, saliva, skin, and They are produced at different depths in targets such as plaque, tooth surfaces and mucosa, thereby inhibiting bacteria, viruses and The agent inactivates, kills, or at least reduces the amount of microorganisms such as bacteria and fungi.

[0077] As shown in the examples with particular reference to one species of Gram-positive bacteria (Streptococcus mutans), This technology is effective against bacteria. Generally, gram-positive bacteria are classified as streptococci. Bacteria genus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus Streptococcus dysgalactiae, Streptococcus bovis, Streptococcus anginosus, Streptococcus sanguinis, Streptococcus suis, Streptococcus Leptococcus mitis and Streptococcus pneumoniae, Staphylococcus genera, e.g. Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus S. simulans, Corynebacterium, Listeria, Bacillus, Clostridium, Lata It is represented by Ibacter, Lifesonia and Clavibacter.

[0078] A further group of bacteria that is of interest to the present technology is the Gram-negative bacteria, e.g., Proteobacteria. Cacteria, Aquifex, Chlamydia, Bacteroides, Chlorobium, Cyanobacteria Teria, Fibrobacter, Verrucomicrobium, Planctomycetes, Spirochetes, Akidobacterium, Actinomycetes, Firmicutes, Thermotoga, Porphyromonas and Chlorella Representative examples include bacteria of the phylum Loflexus. : Escherichia coli, Salmonella enteritidis, Salmonella typhi, Shigella, Pseudomonas, Moraxella, Helicobacter, Stenotrophomonas, Bdellovibrio, Neisseria gonorrhoeae, Neisseria meningitidis, Neisseria catarrhalis Bacillus subtilis, Haemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa, Escherichia coli, Pro Enterobacter mirabilis, Enterobacter cloacae, Serratia marcescens, Helicobacter Bacter pylori, Porphyromonas gingivalis, Aggregatibacter acti Nomiacetemcomitans and Acinetobacter bacteria, e.g. Acinetobacter baumannii manni, Acinetobacter arvensis and Acinetobacter apis.

[0079] This treatment is effective against adenovirus, herpes virus, pox virus, and parvovirus. , reovirus, picornavirus, togavirus, orthomyxovirus, rabudovirus against viruses such as rhesus, retroviruses, papillomaviruses, and hepadnaviruses is also valid.

[0080] The treatment also shows efficacy against fungi such as Candida species, especially Candida albicans. is doing.

[0081] As described in more detail below, the photosensitizer is mixed with a carrier and then applied to the biofilm or target tissue. A solution, gel, paste, or lotion that can be applied to the infected area of ​​tissue or other biological surfaces. and providing the photosensitizer in the form of a patch, a tape, a tablet, or a band-aid. Usually, the photosensitizer is present in an amount of 0.001 to 1% by weight, particularly 0.004 to 0.5% by weight. % concentration of the composition (solution, gel, paste, lotion, salve, tape, table or bag) It is present in the

[0082] The photosensitizer is usually in liquid form, e.g., as a gel, at a concentration of about 0.01 mg / ml to 10 g / ml. ml, for example, 0.1 mg / ml to 1 g / ml.

[0083] In some embodiments, the photosensitizer is typically administered to tissue, biofilm, saliva, skin or It is applied at 0.0001% (w / v) to 1% (w / v) onto target areas such as plaque. .

[0084] In one embodiment, the method according to any of the above embodiments further comprises using an antibacterial photoelectric Using the subcomponents and devices, high-energy photons absorbed by endogenous molecules and exogenous molecules are This is accomplished by simultaneously emitting a photon of low energy that is absorbed by the electron.

[0085] In a further embodiment, an antimicrobial photoelectron for use in a method according to any of the above embodiments. The components and their devices emit high and low energy photons and are The voltage or current is independent of each other at a frequency between 1 Hz and 1 GHz, for example 1 to 100 MHz. The pulses are alternated or pulsed.

[0086] In a further embodiment, an antimicrobial photoelectron for use in a method according to any of the above embodiments. The components and their devices are subjected to high energy (in the range of 2.48 eV to 1.24 eV) photons and Low energy photons (in the range of 3.5 eV to 2.8 eV) are simultaneously emitted. According to an embodiment, the optoelectronic device is configured to photocatalyze endogenous and exogenous molecules or their photodegradation by-products. An optional photodetector for detecting luminescence may be included.

[0087] One embodiment is an optoelectronic component having multiple semiconductor chips connected in series or parallel, The device uses a chip that emits a 2.48 eV to 1.24 eV range. and the emission energy can be changed in the range of 3.5 eV to 2.8 eV. show.

[0088] In an embodiment, the optoelectronic components or devices referred to in the previous two paragraphs each include one .3 eV to 2.4 eV, for example 1.4 to 1.6 eV or 1.45 to 1.56 eV; and It can also emit energy between 0.2eV and 2.9eV, for example 3.17 to 2.95eV. Cut.

[0089] The area of ​​the target to be treated can vary. In one embodiment, the area is about 0.1 cm 2 ~4 cm 2 Such a limited treatment area may be, for example, a portion of the skin or a sensitized area of ​​a mammal. For topical treatment to treat other areas exhibiting infection or biofilm or both. Typically, in another embodiment, the treatment area is about 10-100 cm 2 This area is , applied to dental treatment situations that can be reached using a mouthpiece.

[0090] The power or wattage applied to the target area is typically between 0.01W and 500W, particularly about 0.1 ~50W, for example, varying in the range of 1 to 25W.

[0091] The irradiation dose is about 0.1 to 1000 J / cm 2 , especially 1~500J / cm 2 , e.g. 1~2 50J / cm 2 or 1.5~120J / cm 2 Or 2.5~75J / cm 2 Changes in the range do.

[0092] In one embodiment, the light is 0.001 W / cm 2 ~2kW / cm 2 , preferably 0.01 W / cm 2 ~20W / cm 2 , especially about 0.050 W / cm 2 ~about 10W / cm 2 ,for example Approx. 0.075W / cm2~Approx. 5W / cm 2 , e.g. 0.1 W / cm 2 ~about 2.5W / cm 2 The light is delivered to the target area at a power density of 1000 dpi. This is also called the power density of the light.

[0093] Treatment times vary. Usually, from 0.5 seconds to 120 minutes, especially from 0.5 seconds to 10 minutes, e.g. .5 seconds to 300 seconds or 1 second to 180 seconds.

[0094] Treatment typically results in an increase in temperature in the target area. In one embodiment, the increase in temperature is The temperature varies in the range of about 0.1 to 20°C, for example, 0.2 to 10°C, particularly about 0.5 to 5°C. The local peak temperature at the treatment site remains at the aforementioned value for a limited time (usually less than 30 seconds). , especially for less than 15 seconds).

[0095] In one embodiment, the treatment is performed by using light, particularly non-coherent radiation, at wavelengths between 400 and 430 nm. At one wavelength (corresponding to photons of approximately 3.1 eV to 2.9 eV), preferably 1 to 120 J / cm 2 In particular, the irradiation dose is about 10 to about 2500 mW / cm 2 Power density of 0.5 seconds to 120 minutes and a second wavelength of 780-830 nm (corresponding to photons of approximately 1.59 eV-1.49 eV). is preferably 1 to 120 J / cm 2 In particular, the irradiation dose is about 10 to about 2500 mW / cm 2 The test is carried out by using a power density of 0.5 seconds to 120 minutes.

[0096] In one embodiment according to the present invention, the optoelectronic device is adapted to prevent or therapeutically treat a disease. The present invention is used in a method for generating and delivering photodynamic radiant energy for a subject, the method comprising the steps of: : (i) generating incoherent radiation energy at multiple energy levels; (ii) providing a medium or molecule capable of absorbing at least a portion of the radiant energy; and (ii) A medium or molecule capable of absorbing at least a portion of the radiant energy is called a photoactivator. delivering light energy at a substantially precise light energy wavelength required to activate the Preventive or therapeutic treatment of diseases; (iv) endogenously, exogenously, or both endogenously and exogenously producing active singlet oxygen and active and treating the target prophylactically or therapeutically by generating reactive oxygen species at said target. About.

[0097] One embodiment of the present invention is a method for detecting pathogenic microorganisms, such as bacteria, viruses, or fungi, in an optoelectronic device. It is used for programmed cell death of organisms, with high and low photon and endogenous photosensitive compounds or It is controlled by combining multiple different compounds.

[0098] As mentioned above, in one embodiment, any of the light treatments of the above embodiments may be photodynamic therapy (PDRT). Such treatments are delivered by light and a non-toxic light-activated and a target molecule of the present invention. The target molecule absorbs the energy of the photon to achieve an excited state. The target molecule is then reacted with the ligand by emitting a photon (fluorescence), releasing heat or by forming a so-called triplet state. This triplet state can be escaped by charge transfer (Type I reaction) Or it can react with oxygen by energy transfer (type II reaction). In mechanism I, charge is transferred to the substrate or oxygen molecule, and reactive oxygen species such as hydrogen peroxide are produced. or oxygen radicals such as superoxide ions or free hydroxyl radicals In the Type II mechanism, only energy, not charge, is directly transferred to the oxygen molecule. This transfers the highly reactive singlet oxygen ( 1 O2) occurs.

[0099] The antibacterial effect of PDT is based on an illumination-induced oxidative burst that affects cell structures and molecules. This is a non-specific mechanism, since it is injury-dependent. This burst is highly reactive. The beam is high and has an effective range of less than 0.3 micrometers, allowing treatment to be performed at a specific location. .

[0100] The ratio between different mechanisms of action and activation wavelengths is specific to the target molecule, so PDT Therefore, PTT and PHT treatments must be specifically designed for specific light and target molecule compositions. Some photosensitizers or target molecules have a high ability to generate heat or have triplet states. For example, indocyanine green (ICG) reacts by forming an absorbed In contrast, porphyrin releases more than 80% of the energy absorbed as heat, with the latter releasing only 0.5-0.8%. Thus, the exact mechanism of pathogen killing varies, and therefore the photocatalytic activity of The choice of sensitizer(s) depends on the classification of the treatment: photodynamic, photothermal, or photohyperthermia. It also defines the type.

[0101] The photothermal effect involves the localized heating of pathogens. One possible method of killing pathogens. The method uses pathogen-selective exothermic photosensitizers of appropriate wavelengths to locally heat target pathogens. Biofilms do not have an active blood circulation and are not thermally conductive, so they are difficult to treat with healthy tissue. It has a lower cooling capacity than

[0102] In addition to activating exogenous photosensitizers, the irradiated photons also interact with endogenous molecules of pathogens. The photoreaction of flavins and porphyrins can affect pathogens through It is important in the underlying mechanism of bacterial killing by blue light.

[0103] In bacteria, plant phototropins, blue light-sensing flavin-binding proteins and / or There are several iron-free counterparts of porphyrins. Bacterial flavin photosensors The three major classes of proteins are the LOV (light, oxygen, voltage) domain, the BLUF proteins ( Blue light sensing using flavin adenine dinucleotide (FAD) and cryptography ROHM regulates a variety of biological activities in response to blue light.

[0104] Bacterial LOV proteins contain a variety of effectors bound to the light-responsive LOV domain. Domains such as histidine kinases, transcriptional regulators, putative phosphodiesterases and It has a physiological role as a signaling protein that regulates stress factors. Therefore, the application of specific energy photons determines the cell response to a given treatment. The LOV proteins of many bacteria contain histidine residues, which may alter the bacterial response. It is a member of the protein kinase superfamily. Histidine kinases have multiple functions. In bacteria, it is usually the transcription factor of an enzyme that plays a role in signal transduction through the cell membrane. It is a transmembrane protein of the spherase class. For example, The influx pump may be a histidine kinase. Activation can be located in the periplasm, transmembrane or cytoplasm.

[0105] BLUF proteins mediate the synthesis of light-sensitive proteins that interact with DNA-binding proteins. Many BLUF proteins can regulate the expression of genes related to photosynthesis. Proteins have additional domains downstream of the BLUF domain that have enzymatic or other properties, Most of these proteins appear to be homodimers. For example, the protein BlrP1 Protein is a dimeric cyclic nucleotide phosphodiesterase from Klebsiella pneumoniae that acts under light conditions. The enzyme activity increases fourfold in the presence of the 100-amino acid residues AppA and PAC, which are involved in the detection of light. These are just two examples of the many light-sensitive proteins that contain 100-mer BLUF domains. These are called "group 1" proteins. Many other BLUF proteins are These proteins have less than 10 amino acid residues and are called "group II" proteins. Although each subunit contains only a BLUF domain, it does not contain the secondary structure elements required for stability. It may be present in the terminal region.

[0106] Photolyase and cryptochrome blue light receptors are evolutionarily related to the flava plant Photolyase is a glycoprotein that acts as a glycoprotein in many bacterial species and has different functions. Like cytochromes, it repairs UV-damaged DNA.

[0107] Antiviral treatment involves simultaneously targeting the viral population with three or more antiviral agents.

[0108] Antifungal treatment involves targeting fungal populations simultaneously with one, two, three or more antifungal agents. do.

[0109] As described above, in one embodiment, the cell wall structure, EPS matrix, intercellular signaling, and exogenous effects at the site of administration of the beneficial agent(s), which may consist of the induction of and endogenous effects in which internal molecules of will be carried out.

[0110] This therapy targets key functional sites and outer and inner membrane structures, and inhibits bacterial oxidative stress. Temperature stress induces an oxidative burst that is difficult to control by the thermal response mechanism, and Further destabilizing the cytoplasmic membrane and the cytoplasmic wall. Pathogens and populations of pathogens can attack exogenous and endogenous The described wide range of attacks is different from the conventional method because the oxidation and temperature bursts attack at different sites. This goes far beyond the PDT.

[0111] PDT, PHT and PTT are active molecules or fungicide compounds that disrupt the cell wall structure, Bactericides capable of altering wall stability, external heating of the target area, reactive oxygen transporters, the use of singlet oxygen scavengers that can act as markers to remove divalent ions and Use of ion scavengers to destabilize bacterial cell walls of virulent bacteria; endogenous concentration of photosensitizers the use of ion pump inhibitors to enhance immune response, application of immune response stimulants, and inhibition of microbial efflux pumps. Inhibitors, protein transport (e.g., porin stimulators), and photoactivation of antibiotics or antibacterial substances It can also be enhanced by the addition of topical use as a sensitizer or in combination with a photosensitizer. It is possible.

[0112] One embodiment uses a first photosensitizer during a first period and a different photosensitizer during a second period. The first and second photosensitizers are usually Each can be activated using a first light and a second light. Preferably, the first photosensitizer and the second photosensitizer In combination or alternation with at least one of these drugs during treatment Use at this point.

[0113] In one embodiment, the first photosensitizer is a high-energy photon-activated photosensitizer ("Type-I photosensitizer"). The second photosensitizer is selected from the group consisting of a low energy photon activated photosensitizer and a low energy photon activated photosensitizer. The photosensitizer is selected from the group consisting of type-II photosensitizers.

[0114] One possible approach to treatment is to classify Type I and Type II patients based on the efficacy observed during treatment. The aim of the treatment is to adjust the therapeutic ratio of type I and type II mechanisms. The mechanisms of Type II and Type III can be combined simultaneously or by either mechanism. The therapeutic effect is achieved by adding / replacing compounds that work through the other mechanism at specific intervals. It can be further increased.

[0115] For example, a type II photosensitizer can be combined with low and high energy photons. Periodically add a type I photosensitizer or pigment that generates active oxygen in a charge transfer process. One possible combination is the type II photosensitizer indocyanine green and Combining the Type I photosensitizer curcumin with high- and low-energy photons It is also possible to monitor treatment and change mechanisms when certain events are detected. It is possible.

[0116] In one embodiment, the light can be pulsed to allow for the replenishment of target molecules such as oxygen during the dark period. or by adding additional targeted molecules to the treatment, oxygen-generating compounds such as superoxide dismutase or peroxo compounds. Enhancement of the treatment may be achieved by adding, for example, hydrogen peroxide. The aim is to increase the amount of oxygen present in order to enhance the effectiveness of dynamic therapy.

[0117] The wait time between pulses can be between 0.01 and 100 times the length of the treatment pulse. This is especially important since maximum therapeutic output is limited by heat generation and heat loss. By directing the light in a way that produces a stimulant effect, the treatment becomes more effective and the time required for treatment becomes shorter. do.

[0118] Typically, the treatment pulse time is 0.01 to 120 seconds, particularly 0.5 to 60 seconds, e.g., 0.5 to 3 The range is 0 seconds.

[0119] Using high and low energy photons allows the different energy photons to have different It is beneficial because it has tissue stimulating properties. Low energy photons can produce beneficial tissue heating of 2.7°C. This increases oxygen pressure and blood circulation, This then stimulates cellular metabolism, including promoting the immune response.

[0120] High-energy photons, especially those with an energy of 3.06 eV, have been shown to have an intrinsic bacterial killing effect. These same target molecules may be more than one. Photon upconversion in which the upper photon is simultaneously absorbed to excite the target molecule to a higher energy state It can be activated by a version reaction.

[0121] In one embodiment, the selection of 3.06 eV and 1.53 eV is a particularly good combination. 1.53 eV (corresponding to a wavelength of 810 nm) is 3.06 eV (corresponding to a wavelength of 405 nm) It has exactly half the photon energy of the ion beam (IR) but has much higher tissue penetration. Therefore, by simultaneously absorbing 1.53 eV and 3.06 eV photons, the intrinsic porphyrin It excites rufilin, and can achieve antibacterial effects in addition to tissue healing effects. -Photons reduced the formation of the extracellular polysaccharide matrix of biofilms and were associated with exogenous PDT The synergistic effect reduces the pathogenicity of biofilms.

[0122] The present invention relates to a method for treating the disease caused by pathogens such as bacteria, viruses and / or fungi on the skin, in the mouth, teeth, etc. It is suitable for treating conditions affecting the face, gums, mucous membranes, throat and genitals.

[0123] The method can also be practiced to use only light to stimulate tissue.

[0124] Because PDT treatment is nonspecific, it is inherently difficult to develop resistance to it. The robustness of PDT treatment depends on the different mechanisms that function via singlet oxygen, charge transfer, and heat generation. This can be enhanced by the use of certain types of photosensitizers. Photothermal therapy, which has these two aspects, is fundamentally more robust than PDT. These have a synergistic effect and when combined they create a very effective system.

[0125] Even though the treatment is very robust, selection for more resistant bacterial species does occur. In the oral cavity, this can be achieved by concentrating treatment on the desired area and leaving other areas untreated. This reduces the oral flora compared to antibacterial mouthwashes. Minimize changes in the surface of the teeth and gums and effectively kill bacteria in targeted areas It is possible.

[0126] Light systems are known to penetrate deep into tissue and stimulate blood circulation and immune responses. The tissue stimulating light may also include near infrared light, which is used in the imaging of the patient.

[0127] Light can also be used to stimulate bone formation in teeth, and heat can be used to stimulate PDT and P In addition to enhancing TT treatment, it can increase fluoride binding to enamel. Cut.

[0128] The device serves an important function as a heating surface to enhance the therapeutic effect and increase the binding rate of fluoride. The fluoride and photosensitizer penetrate deep into the biofilm by thermal diffusion. This will further enhance the therapeutic effect.

[0129] When the biofilm becomes a mature biofilm after 0 to 96 hours, The metabolism and bacterial composition of the film are changed. This changes the biofilm phase to 0 h. , 12 hours, 24 hours, 32 hours, 48 ​​hours, 72 hours and 96 hours, if different, There is pressure on PDT treatment as different treatments are required to achieve an efficient overall treatment outcome. Light.

[0130] Photosensitizers can be highly specific to biofilms, exploiting their unique optical and photochemical properties (reflection, photochemical, and photochemical properties). The methods used to measure the extent and thickness of bacterial biofilms include: The absorbed light also heats the target tissue, providing a means of detecting and measuring the temperature of different tissues. By comparing the temperature difference between different locations, the health of tissue can be measured. Thermal monitoring can be used to measure the cooling capacity of tissue or inflamed tissue, which has a lower cooling capacity than healthy tissue. Cancer tissue or inflammation can be detected. Absorption and time-dependent fading and fluorescence intensity It can be used to measure the thickness of the biofilm and the amount of bacteria, and therefore to detect disease at the target site. Monitoring can be particularly useful in the treatment of chronic conditions, such as heart disease, stroke, and stroke. Helps monitor periodontitis and gum health and aids in early cancer detection.

[0131] For treatment monitoring purposes and ongoing treatment safety, and monitored with a fluorescence microscope set to monitor the absorption maximum of the photosensitizer. In addition, light absorption was higher in the target biofilm compared to clean dentin or healthy tissue. Monitoring data can be used to monitor changes during treatment. Treatment options include bleaching of one or more photosensitizers or directing output to areas rich in biofilm. Plan and implement individualized treatment options, such as adjusting treatment or more frequent use, to accommodate the needs of the individual. Mechanical cleaning can be focused on specific areas and professional visits can be recommended.

[0132] The difference in light absorption and enamel absorption between areas where remineralization is progressing and areas where enamel has been lost Luminescence can be used to monitor the mineralization process, especially when blue and NIR light are used together. By using this method, deep caries as well as surface changes in the teeth and enamel can be detected at the same time. do.

[0133] Indocyanine green undergoes a red shift when bound to pathogens. By measuring the photobleaching rate, biofilm and its total mass can be quantified and characterized. The total absorption and photobleaching rates are a function of the thickness of the biofilm and the amount of active material in the biofilm. It also uses spectroscopic analysis to measure sugar levels, pH levels, fat , calorie content, protein content, and amount of extracellular polymeric substances in the biofilm. Plaque characteristics can be detected. For these purposes, photoelectron The devices include microspectrometer sensors, temperature sensors, light sensors, pH sensors, force sensors, Sensors, gyroscopes and pressure sensors can be incorporated.

[0134] When two or more photons are absorbed simultaneously, superexcited states with distinct fluorescent and chemical properties are created. The energy of the superexcited state is higher than that of the normal excited state. The rate of formation of superexcited states can be used to quantify biofilm thickness and identify disease sites deep within tissue. The drug substance can be detected.

[0135] As mentioned above, the therapeutic effect is due to the inhibition of microbial efflux pumps, the external and internal Effects on the EPS matrix, pathogen-pathogen communication or quorum sensing The effect of destruction on the external structure of the pathogen, the supply of high concentrations of oxygen or reactive oxygen to the target site, Stimulation of immune response, promotion of oxidative stress transmission, enzyme utilization, and control of pathogens and biofilms Increased uptake of active substances, chemical quenchers of singlet oxygen (carotenoids, beta-carotene, etc.) The effect can be enhanced by the addition of, for example, lutein and α-tocopherol.

[0136] Addition of inorganic salts, especially potassium iodide, divalent ions, germicides, carrier fluids and topical antibiotics Photons can be used to activate and enhance the effects of local antibiotics. and inhibiting or preventing the development of antibiotic resistance in bacteria in conjunction with such antibiotic treatment. It can inhibit inflammation and stimulate tissue healing and immune responses.

[0137] Treatment is combined with topical antibiotics and fungicides to provide a synergistic antipathogenic effect. For example, phototherapy with chlorhexidine targeted to biofilms can be used. Therapy is a new method for oral disinfection. Dual-wavelength photodynamic therapy with chlorhexidine for Streptococcus tanneri biofilms The results are entirely new. High- and low-energy photons, together with a photosensitizer, By using this, the antibacterial effect against biofilms is significantly improved, making it possible to treat biofilms. This study provides a promising new approach to improve the efficacy of photons and anionic photosensitizers. Deeply penetrates biofilms and effectively kills bacteria both inside and on the surface of the biofilm The efficacy of chlorhexidine is based on its ability to inhibit the growth of bacteria on the surface of biofilms. High-energy photons stimulate the formation of the EPS matrix in biofilms. This reduces the amount of chlorhexidine in the blood and further enhances the effectiveness of subsequent chlorhexidine treatments.

[0138] Methods for applying the active ingredient to the target site include aqueous solutions, alcohol-containing solutions, chlorohexane, sidine-containing solution, hydrophilic gel, hydrophobic gel, hydrophilic polymer, hydrophobic polymer, paste , lotions, tapes, salves or band-aids.

[0139] Aqueous solutions of the above type include mouthwashes. In particular, the photosensitizer is chlorhexidine. It is used in conjunction with a mouthwash or mouthwash.

[0140] In one embodiment, the beneficial agent is a polymer, an inorganic molecular network, a nano / microparticle, Fiber aggregates, fiber networks, nonwoven fabrics, foams, hydrogels, pastes or any of these Films, gels, and emulsions with thicknesses of 1 nm to 10 mm can be made from a combination of the following components: The antibody is delivered by a device which may be

[0141] The substrate containing the beneficial agent may be mounted on or within an optoelectronic device that emits light. The optical fiber may be disposed or located separately from the optoelectronic device.

[0142] In one embodiment, the beneficial agent, such as ICG, is provided with a glycerol-containing amine ester that enhances storage stability and eases administration. To achieve this, the beneficial agent is held in a hydrophobic or amphiphilic medium. This can be achieved by incorporating the compound into a hydrophobic or amphiphilic carrier liquid or gel. One example of such an application is a gel that uses DMSO as the main solvent. For example, gels with gel-like properties, such as gels whose one component is polydimethylsiloxane (PDSM), The gel can be classified as a sustained release gel, and the active substance is They can be incorporated into the gel alone or together with molecules classified as antibiotics.

[0143] An organic or inorganic compound embedded with a photosensitizer and optionally one or more enhancement compounds. A film, gel or emulsion made of a polymer. Films, gels and emulsions The film has capillary action, so when placed on a damp surface it will absorb water. The films, gels and emulsions are transparent to the therapeutic light. is applied to the treatment surface for subsequent treatments and to protect the site from other pathogens and dirt. The specific use of the film, gel or emulsion may be Uses include treating aphthous stomatitis lesions, herpes sores, and skin wounds.

[0144] The film, gel or emulsion can be made partially or completely water soluble, The polymers are pullulan, hydroxypropyl cellulose, polyvinylpyrrolidone, carbo Dioxymethylcellulose, polyvinyl alcohol, sodium alginate, polyethylene glycol Recall, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum Polyacrylic acid, methyl methacrylate copolymer, carboxyvinyl polymer, amylase high amylase starch, hydroxypropyl high amylase starch, dextran Torin, pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, gel The preferred dietary fiber is glycerin, gluten, soy protein isolate, whey protein isolate or casein.

[0145] The two light sources can be manufactured within the same LED housing or integrated into a single light emitting surface. The amount of high-energy photons and low-energy photons emitted varies from 50%-50% to 1%-9%. 9% or conversely it could be 99%-1% or anything in between. Low Energy Light and High Energy Light When these two are combined, the photons act via different mechanisms and have different optical properties, which is what we need. The total intensity is lower than that of high-energy or low-energy photons alone, so It's an eye-safe solution.

[0146] The ratio of high-energy and low-energy photons can be adjusted to detect different bacteria at different times. It is possible to target biofilms of species.

[0147] In one embodiment, the ratio of emitted high energy photons to emitted low energy photons is 0.2: 1~5:1, especially 1:1~3:1.

[0148] In one embodiment, the light source or optoelectronic device uses high energy photons to detect bacterial genomes. It is possible to provide dual wave therapy that stimulates gene expression and enhances the therapeutic effect in the long term.

[0149] Based on the above, the first embodiment is a method for producing a 2.8 eV to 3.5 eV photosensitizer with or without a photosensitizer. High energy photons with most of their energy between 1.24 eV and 3.5 eV Photoelectrons capable of emitting low-energy photons with most of their energy between 5 eV A device for sustained use in preventive and therapeutic dental / oral care for long-term use. The present invention provides an optoelectronic device that enables a method for effective antimicrobial effects.

[0150] A second embodiment is a method for detecting two wavelengths simultaneously or within 0.001 to 1000 milliseconds of each other. For example, an optoelectronic device of the type described above is provided that emits at time intervals of about 100 milliseconds.

[0151] An optoelectronic device may include a light emitting component having two or more light emitting surfaces (EPIs).

[0152] The optoelectronic device may also include sensors that can monitor the progress of treatment, plaque volume The optoelectronic device can adjust the therapeutic light based on the monitor's feedback. It is preferable to be able to do so.

[0153] There are many possible designs for optoelectronic devices. The device is shaped like a toothbrush. The photoelectron device used in the treatment may be a mouthpiece or a rod-shaped light fixture. The products include microspectrometer sensors, temperature sensors, light sensors, pH sensors, and force sensors. It may incorporate sensors such as a gyroscope and pressure sensors.

[0154] Based on the above, the present technology can be used to detect tissues, biofilms, saliva, skin, dental plaque, dental surfaces, and Kits for treating microbial, viral or fungal infections of mucosal membranes are also provided.

[0155] In one embodiment, the kit comprises at least two components: an optoelectronic component or device thereof; The optoelectronic component or device comprises a substrate and at least one photosensitizer. It is possible to simultaneously emit a first light consisting of high-energy photons and a second light consisting of low-energy photons. Typically, the first light and the second light are at least a fraction of the total light emitted from an optoelectronic component or device. Photosensitizers are used to detect a small amount of high-energy and low-energy photons. It is a type that can be activated by at least one of two things: high-energy photons and low-energy photons. It is also possible to use photosensitizers that can be activated by both photons and ultraviolet light. may be of any of the above types.

[0156] In a second embodiment, the kit has most of its energy between 2.8 eV and 3.5 eV. High energy photons with most of their energy between 1.24eV and 1.65eV The optoelectronic device capable of emitting low energy photons is provided with a photosensitizer or a plurality of photosensitizers. Contains anti-inflammatory and anti-inflammatory agents for long-term use in preventive and therapeutic dental / oral care. Methods can be implemented to achieve a fungicidal effect.

[0157] A third embodiment is an optoelectronic device of the kind specifically disclosed above, comprising two wavelengths simultaneously or from 0.001 milliseconds to 10 seconds or from 0.001 milliseconds to 1000 milliseconds Photoelectron devices that emit light at time intervals of 10 to 500 milliseconds or about 100 milliseconds. and optionally a photosensitizer or photosensitizers, A method for achieving sustained antibacterial efficacy in preventive and therapeutic dental / oral care for Kits are provided that allow the methods to be carried out.

[0158] In one alternative, the LED or LEDs are driven at a frequency between 1 and 50 MHz, for example at about 10 It is pulsed at a high frequency, such as MHz, to obtain high and low energy photons.

[0159] A fourth embodiment is an optoelectronic device having a light emitting component with two or more light emitting surfaces (EPIs). and optionally a photosensitizer or photosensitizers, A method for achieving sustained antibacterial efficacy in preventive and therapeutic dental / oral care for Kits are provided that allow the methods to be carried out.

[0160] A fifth embodiment includes an optoelectronic device according to any of the previous embodiments, The kit further includes a sensor capable of monitoring the progression of the treatment. A sensor capable of detecting the progression of a therapeutic agent and generating a regulatory signal based on the progression of the therapeutic agent. an optoelectronic device including a sensor, the sensor being coupled to the optoelectronic device, The optoelectronic device includes an optoelectronic device that modulates light emitted from the optoelectronic device in response to a signal.

[0161] A sixth embodiment is a toothbrush shaped or insertable in the mouth between the biting surfaces of the teeth. A kit is provided that includes an optoelectronic device further exhibiting a mouthpiece shape or a bar-shaped lighting fixture shape. Provide.

[0162] The optoelectronic device used in any kit or treatment may be a microspectrometer sensor. temperature sensor, light sensor, pH sensor, force sensor, gyroscope and pressure sensor It can be incorporated.

[0163] In the above disclosed embodiments, the optoelectronic device preferably comprises a semiconductor light source, in particular In some embodiments, the light source may be a light emitting diode (LED). The LED light source may have one or more light emitting surfaces. The amount and power of light emitted from the LED can be controlled by external This can be varied by adjusting the input power from the power supply.

[0164] In a preferred embodiment, the optoelectronic device, in particular the LED device, emits non-coherent radiation. At the first wavelength of 400-430 nm (corresponding to photons of approximately 3.1 eV-2.9 eV), Preferably 1 to 120 J / cm 2 In particular, the irradiation dose is about 10 to about 2500 mW / cm 2 Electricity Power density from 0.5 seconds to 120 minutes and second wavelength of 780 to 830 nm (approximately 1.59 eV 1.49 eV photon), preferably 1 to 120 J / cm 2 At a dose of approx. 10~about 2500mW / cm 2 It can be emitted for 0.5 seconds to 120 minutes at a power density of .

[0165] In any of the above embodiments, the targeted photosensitizer or high energy photons or Photosensitizers that receive photons, low-energy photons, or both are photoexcited to undergo photodynamic reactions. Note that the molecule may be one or more unique molecules capable of binding to the target molecule.

[0166] The following represent further embodiments.

[0167] The device detects the progress and status of treatment with a radiation sensitive sensor or sensors. A kit that can detect changes in the optical properties of indocyanine green, changes in temperature, etc. Or, fading of indocyanine green is detected.

[0168] A kit in which the tooth whitening material is used in conjunction with a dual wavelength light source or in conjunction with a photosensitizer.

[0169] A kit comprising an active substance in an easy-to-apply form and a light irradiator capable of dual light activation.

[0170] A photosensitizer in the form of a water-soluble effervescent tablet and a handheld light source capable of emitting dual light photons. A kit including a launcher.

[0171] Photosensitizer in the form of a water-soluble effervescent tablet, gel or paste, and a one-time use mouthpiece A kit comprising a light source and a light irradiator.

[0172] The photosensitizer in the kit may be, for example, a berry extract mouthwash that is incorporated or is naturally present in the berry extract mouthwash. The photosensitizer may be provided in the form of a photosensitizer.

[0173] The kit may also include hydrogen peroxide as a potentiating compound.

[0174] Furthermore, based on the foregoing, the following represent preferred embodiments.

[0175] 1. A composition comprising a photosensitizer and a medium, the medium being (i) an aqueous phase; (ii) high-energy photons with most of their energy between 2.8 eV and 3.5 eV; (iii) Low-energy light with most of its energy between 1.24 eV and 1.65 eV A composition comprising:

[0176] 2. A composition comprising a photosensitive compound and a medium, the medium being (i) PDMS gel; (ii) biofilms; (iii) High-energy photons with most of their energy between 2.8 eV and 3.5 eV ; (iv) Low-energy photons with most of their energy between 1.24 eV and 1.65 eV and a composition comprising:

[0177] 3. The photosensitive compound has photon absorption in the energy range of 1.24 eV to 1.65 eV. 3. The composition of embodiment 1 or 2, wherein the composition is selected from the group consisting of:

[0178] 4. Any of embodiments 1 to 3, wherein the photosensitive compound is indocyanine green. The composition described in claim 1.

[0179] 5. The photon has at least 50% of its energy between 3.17 eV and 2.95 eV and 1. The composition according to any one of embodiments 1 to 4, having a polarization energy between 56 eV and 1.45 eV.

[0180] (experiment) In the first series of tests, after treatment with Hamamatsu 1394 and a NIR light source, The specificity of stained plaque was observed under room light.

[0181] As can be seen in Figures 1 and 2, respectively, the non-biofilm and biofilm areas of the teeth and gums were There is a clear intensity difference between the areas where the film is present. , and in Figure 2 we focus on the biofilm regions with low grey values.

[0182] In a second series of studies, we evaluated the effect of chlorhexidine augmentation with dual-wavelength PDT. The results are shown in Figure 3, which shows that the combination of multi-wavelength PDT and chlorhexidine , showing that it produces a much stronger effect than the reference and treatment with only one wavelength. .

[0183] In the third series of studies, mutants were compared in response to multi-wavelength and single-wavelength PDT treatments, respectively. The fitness of streptococcal biofilms was compared.

[0184] To investigate the effect of repeated photodynamic therapy on biofilm formation, two separate A single-species biofilm model experiment was conducted. The experiments were divided into different classes based on the stage of the biofilm and the treatment given.

[0185] Biofilms on days 1, 2, and 4 were treated with a single PDT treatment. This effect was confirmed by the strong inhibition of biofilm growth in the daily treated samples. We hypothesized that the survival rate of bacteria in the biofilms on the fourth day of daily treatment was significantly higher than that in the final The cells were assessed by serial dilution CFU assay performed after photodynamic therapy.

[0186] Materials and Methods Mutans streptococci (ATCC 25175) were cultured in an incubation chamber (36 °C, 5% CO 2) and cultured in BHI broth (Bio-Rad 3564014) for 18 hours. The bacterial suspension was diluted with 0.9% NaCl suspension and the optical density was adjusted to 0.46.

[0187] Add 100 ul of diluted mutans streptococcus suspension to 100 ul of BHI broth growth medium. The bacterial plate was then added to each well along with 100% ethanol, and a biofilm was allowed to grow on the bottom of the well plate. The plates were incubated in an incubation chamber (36 degrees Celsius, 5% CO2) and incubated in BHI broth medium. The land was changed every day.

[0188] (irradiation) Before the light exposure, the growth medium was replaced with an indocyanine green suspension and incubated at room temperature for 10 min in the dark. After incubation, the biofilm was soaked in 0.9% NaCl water. The solution was washed twice and the treatment time was calculated based on the desired light dose and known intensity.

[0189] Illumination was achieved by placing the well plate under an LED light source of known light intensity. was analyzed with a Thorlabs PM100D and S121C sensor head. The treatment time was varied to obtain the desired amount of light.

[0190] CFU: After irradiation, mechanically remove the biofilm from the bottom of the well plate using a sterile inoculation rod. The biofilm was removed from the wells by scraping with a cloth. The resulting bacterial suspension was then 100 ul of the solution was plated on BHI plates at various dilutions between 1:1 and 1:10,000. I sowed it.

[0191] (Tests and Results) Initial studies of continuous treatment of streptococcal biofilms with PDT were performed at 250ug / ml The study was carried out using 100 mg of ICG with 810 nm light. Biofilms of different ages were grown and each biofilm was treated once. The effect of a single treatment on biofilms was evaluated.

[0192] In addition to these three studies, grow biofilms on day 4 that receive daily PDT treatment. The initial hypothesis was that biofilms treated daily would have nearly zero CFU. The results of single wavelength treatment are shown in Figure 10, which shows the results of the first, second and fourth days of myocardial infarction. This shows the efficacy of PDT treatment against Streptococcus mutans biofilm. Day 4 Two variations of the biofilm were performed: one every day and one only on the fourth day. The patient received PDT treatment.

[0193] The increase in total bacterial load over time in the control and in the biofilm model As expected, the strong effect of PDT treatment on the biofilms was The poor therapeutic effect of photodynamic therapy is widely believed to be due to the inability of bacteria to acquire resistance to photodynamic therapy. This was a surprising observation, since the chromosomes are well known to be chromosome-specific. All of the above experiments were repeated at least three times. This finding was verified in 12 replicates of biofilms that were treated daily for 4 days.

[0194] A similar effect was not seen when combined treatment was used. The researchers combined a combination of antimicrobial and antibacterial therapies to target biofilms and kill Streptococcus mutans. To destroy it, 70 J / cm 2 The bacterial plate test showed that 100% of 405 nm light was needed. In a double combination experiment, red light (peak at 810 nm) and blue light (peak at 820 nm) In the multiple light experiments, we focused on investigating the resistance induction effect. To address this issue, we focused on the 4-day biofilm model and performed light treatment every day and for 4 days. The hypothesis was that daily treatment would have the worst outcomes, as previously observed. The experimental results are shown in Figure 11.

[0195] FIG. 11 shows biomarkers on the fourth day after treatment with dual-wavelength and single-wavelength PDT systems, respectively. 1 is a bar graph showing the film. For dual-wavelength PDT, between daily treatment and 4-day treatment. No significant difference was observed in the bactericidal effect between the two groups, but continuous treatment with single-wavelength PDT showed a strong bactericidal effect. could not achieve the results.

[0196] Therefore, dual-wavelength light therapy is more effective and improves bacterial bioavailability. No film adaptation was observed.

[0197] Targeting biofilms by simultaneously combining endogenous and exogenous photodynamic therapy It is believed that this will improve the efficiency of PDT with 40 Shows the antibacterial effect of 5 nm light treatment.

[0198] As is clear from the figure, the 405 nm light has a power of 70 J / cm 2 High energy density exceeding Only at these high concentrations can PDT be shown to be highly effective against mutans streptococci. In the 1990s, the killing effect was much stronger. Already at 4 J / cm 2 At a dose of 1000, mutans strain The growth of the cocci was completely inhibited.

[0199] Finally, a fourth series of tests showed similar results to those above for the treatment of gram-(-) bacteria. It should be noted that was obtained.

[0200] Different cell wall structures are sensitive to different photosensitizers, resulting in Gram-negative Compared with conventional PDT, which may lack efficacy against either virulent or positive bacteria The use of high-energy and low-energy photons in conjunction with photosensitizers has been shown to be effective in the detection of gram-positive bacteria and It has a more excellent, stable and strong antibacterial effect against gram-negative bacteria. High energy photons have minimal impact on the balance of gram-negative and gram-positive bacteria in the area. and low energy photon therapy is recommended for use with active substances.

[0201] Figure 7 shows the antibacterial effect of PDT treatment on mutans streptococcus biofilms after 14 days. The left bar of each pair shows the results of treatment with 100 J of light, while the right bar shows the results of treatment with 100 J of light. represents the results of treatment with 50 J of light (1 cm 2 As will become clear later The phototherapy of the present invention has been proven to be highly effective against microorganisms. [Industrial Applicability]

[0202] The present invention can be used to treat biological surfaces. In particular, the method of the present invention involves treating a surface A biological surface is a biological surface formed by microorganisms. Any surface that is or may be contaminated, typically biological tissue and its surfaces. Such biological contamination is usually caused by biofilms and biofilm infections. Diseases such as dental infections and skin infections caused by dental plaque, urinary tract infections, middle ear infections, endocarditis The treatment is mainly used for the treatment of superficial inflammation and implant- or catheter-related infections. To prevent or reduce biological contamination of living tissue, e.g. contamination of living tissue with microorganisms, viruses or fungi. This treatment is not only for cosmetic purposes, but also has antibacterial and antiviral properties. It can also be used for antifungal treatment. It is therefore generally used in tissues, biofilms, saliva, etc. Viral or fungal infections of the blood, skin, dental plaque, dental surfaces and mucous membranes. It can also be used to treat other biological materials that have surfaces. For example, biofilms Such biofilms are generally found on equipment and parts of equipment that are covered with Found in industrial water systems, medical and process industries including the pulp and paper industry, and the food industry obtain.

Claims

1. A first light beam is a beam of photons having most of their energy in the range of 3.5 eV to 2.8 eV; The second light is generated by photons with most of their energy in the range of 24 eV to 2.48 eV. A method for treating a biological surface with electromagnetic radiation in the form of light at different energy levels, and irradiating the biological surface with photons of the first light and the second light simultaneously.

2. 2. The method of claim 1 , The incoherent radiation energy is then distributed to at least two of the first and second energy levels. at different energy levels; A majority of the energy of the first energy level is extracted from the incoherent radiation energy. a first light having a wavelength corresponding to a majority of the energy of the second energy level; and a second light having a wavelength corresponding to said first light; The method comprises irradiating the first light and the second light simultaneously onto a biological surface.

3. 3. The method according to claim 1 or 2, wherein the biological material on the surface is, in particular, reactive singlet oxygen or and / or reactive oxygen species, which undergo endogenous and exogenous excitation. Law.

4. Prevent or reduce biological contamination of surfaces, such as contamination of biological tissue with microorganisms, viruses or fungi. The method of any one of claims 1 to 3, wherein said step of determining whether said detection is successful comprises taking measures.

5. Any of claims 1 to 4, including cosmetic treatment or antibacterial, antiviral or antifungal treatment. The method according to any one of claims 1 to 5.

6. The method according to any one of claims 1 to 5, wherein the light is used as is.

7. and applying the light to at least one photosensitizer to treat the surface using photodynamic therapy. The method according to any one of claims 1 to 6, in combination with a substance.

8. The high energy photons and the low energy photons can be activated by the low energy photons. The method according to any one of claims 1 to 7, wherein the irradiation is performed in combination with at least one exogenous photosensitizer. The method described.

9. The present invention provides a photosensitizer for use in the localized treatment of mammalian tissue, the photosensitizer being administered to a mammal. The composition is applied to a surface area of ​​said tissue, such as the skin or mucosa, and the area thus treated is subsequently The method according to any one of claims 1 to 8, further comprising exposing the substrate to light of two different wavelengths either simultaneously or in parallel. 。

10. The light is high energy photons having most of their energy between 2.8 eV and 3.5 eV. The first light by; the low energy light with most of its energy between 1.24 eV and 1.65 eV The method according to any one of claims 1 to 9, further comprising a second light of Gamma photons.

11. The photosensitizer is applied to targets such as tissue, biofilm, saliva, skin, dental plaque, and dental surfaces or mucosa. Microorganisms such as bacteria, viruses, or fungi that exist naturally in water, alcohol-containing solutions, parenteral solutions, etc. Aqueous gel, hydrophobic gel, hydrophilic polymer, hydrophobic polymer or paste, lotion, tape The target is contacted by application to the target in the form of a cream, tablet, salve, or band-aid. The method according to any one of claims 1 to 10,

12. The biological surface may be tissue, biofilm, saliva, skin, plaque and dental surfaces, and mucous membranes. The method according to any one of claims 1 to 11, wherein the compound is selected from the group consisting of

13. A method according to any one of claims 1 to 12, comprising a non-therapeutic treatment of a biological surface.

14. High-energy photons absorbed by endogenous molecules and low-energy photons absorbed by exogenous molecules Any of claims 1 to 13, wherein the energy photons are emitted simultaneously from an optoelectronic component or device. The method according to any one of claims 1 to 5.

15. High-energy photons and low-energy photons are alternated or slightly alternating at frequencies between 1 Hz and 1 GHz. comprises emitting independently of each other using a pulsed supply voltage or current.

15. The method according to any one of claims 1 to 14.

16. An optoelectronic device, including an optional detector such as a photodetector, is used to detect intrinsic and extrinsic Detecting the photoluminescence of molecules or their photolysis by-products.

6. The method according to any one of claims 5 to 5.

17. Using an optoelectronic device having multiple semiconductor chips connected in series or parallel and the tip has a range of 2.48 eV to 1.24 eV and a range of 3.5 eV to 2.8 eV. Any one of claims 1 to 16, which shows a light emission energy that can be changed within the range of The method according to any one of claims 1 to 5.

18. A first photosensitizer is used during a first period, and a second photosensitizer different from the first photosensitizer is used during a second period. The method of any one of claims 1 to 17, comprising using a sensitizer.

19. The first photosensitizer and the second photosensitizer are activated with a first light and a second light, respectively. The method according to claim 17 or 18,

20. The first photosensitizer is used in combination or alternation or at least one of them. The method according to any one of claims 17 to 19, wherein at a predetermined time during said treatment,

21. The photosensitizer(s) may be hypericin, curcumin, a phenalenone derivative, or a selenium derivative. Leucosporin, psoralen, xanthotoxin, angelicin, α-terthienyl, phenyl Naturals containing lutein, THC, cannabidiol (CBD) and combinations thereof From the group of natural compounds, as well as RB (Rose Bengal), MB, porphyrin derivatives, curcumin derivatives, methylene blue, indocinine green, erythrocin, phenalenone derivatives, From a group of synthetic photosensitizers including fullerene derivatives, xanthene derivatives and combinations thereof or at least one photosensitizer is selected from the group of natural compounds described above, Any one of claims 1 to 20, wherein at least one photosensitizer is selected from the group of synthetic compounds described above.

3. The method according to claim 1 .

22. Light energy, particularly non-coherent radiation energy, is irradiated with a first wavelength of 400 to 430 nm. In the long run, preferably 1 to 120 J / cm ２ In particular, the irradiation amount is about 10 to about 2500 mW / c m ２ At a power density of 0.5 seconds to 120 minutes and a second wavelength of 780 to 830 nm, Or 1 to 120 J / cm ２ In particular, the irradiation amount is about 10 to about 2500 mW / cm ２ Power density The method according to any one of claims 1 to 21, wherein the biological surface is irradiated with 1000 nm of ultraviolet light for 0.5 seconds to 120 minutes. How to.

23. 23. Any of claims 1 to 22, wherein the light is generated by one or more light emitting diodes.

3. The method according to claim 1 .

24. A sensitizer for use in the topical treatment of an infection in a mammal, comprising applying the sensitizer to the skin or A portion of the mucous membrane is then subsequently or simultaneously exposed to a large amount of radiation between 2.8 eV and 3.5 eV. The first photon has an energy of 1.24 eV to 1.65 eV, and the majority of the energy is between 1.24 eV and 1.65 eV. Expose the sensitizer to a second photon with a .

25. The infection may be caused by the microorganisms of tissues, biofilms, saliva, skin, dental plaque, dental surfaces and mucous membranes.

23. The method of claim 22 for use in the topical treatment of an infectious disease in a mammal, the infectious disease being a viral or fungal infection. A sensitizer for use in

26. A sensitizer for use in the topical treatment of an infectious disease in a mammal according to claim 23 or 24. Hypericin, curcumin, phenalenone derivatives, cercosporin, psoralen, kisamine toxin, angelicin, α-terthienyl, phenyltepatriin, THC, can From the group of natural compounds including cannabidiol (CBD) and combinations thereof, as well as RB ( Rose Bengal), MB, porphyrin derivatives, curcumin derivatives, methylene blue, Docinine green, erythrocin, phenalenone derivatives, fullerene derivatives, xanthene Derivatives, resveratrol, polyphenol compounds and / or anthocyanin compounds Extracts of berries such as lingonberries and blueberries, including combinations thereof or a compound comprising at least one photosensitizer selected from the group of synthetic photosensitizers comprising The agent is at least one photosensitizer selected from the group of natural compounds described above, and at least one The photosensitizer is a combination selected from the group of synthetic compounds described above.

27. In treating mammalian oral biofilm conditions characterized by caries formation and periodontitis. A combination of an antimicrobial agent and a photosensitizer for simultaneous, separate or sequential use. The antibacterial factor is an antibacterial blue light, a bactericide, an active oxygen generator, and an oxygen transport agent. A combination of an antimicrobial agent and a photosensitizer, comprising at least one of the following:

28. The photosensitizer is exposed to light energy, particularly non-coherent radiation energy, at a concentration of 400 to 4 At a first wavelength of 30 nm, preferably 1 to 120 J / cm ２ In particular, the irradiation amount is about 10 to about 2500mW / cm ２ for 0.5 seconds to 120 minutes and At two wavelengths, preferably 1 to 120 J / cm ２ In particular, the irradiation amount is about 10 to about 2500 mW. / cm ２ 27. The method according to claim 24, wherein the power density is 0.5 s to 120 min. A sensitizer for the use as described or a combination for the use as described in claim 27.

29. Microorganisms, viruses or other pathogens in tissues, biofilms, saliva, skin, dental plaque, dental surfaces and mucous membranes A kit for treating a fungal infection, comprising a first light of high energy photons and a second light of low energy photons. an optoelectronic device capable of simultaneously emitting a second light consisting of energy photons (said first light) and the second light is at least 8% of the total light emitted from the optoelectronic component or device. 0%) and high-energy and / or low-energy photons. and at least one photosensitizer that can be activated by the

30. High energy photons with most of their energy between 2.8 eV and 3.5 eV and 1.2 Emitting low-energy photons with most of the energy between 4 eV and 1.65 eV A kit comprising an optoelectronic device capable of detecting a long-term photosensitizer or a plurality of photosensitizers. Achieving sustained antimicrobial efficacy in preventive and therapeutic dental / oral care for prolonged use A kit capable of carrying out the method for:

31. The two wavelengths may be simultaneously or at intervals of 0.001 to 1000 milliseconds from each other, for example about 100 milliseconds. Photoelectric devices, in particular of the type disclosed in claims 29 or 30, capable of emitting light at time intervals of seconds. A kit comprising a child device, optionally together with a photosensitizer or photosensitizers, For use in preventive and therapeutic dental / oral care to achieve sustained antibacterial efficacy A kit capable of carrying out the method for

32. An optoelectronic device having a light emitting component with two or more light emitting surfaces (EPIs), optionally A kit containing a photosensitizer or a plurality of photosensitizers, as well as prophylactic and therapeutic agents for long-term use. It is important to implement methods to achieve sustained antimicrobial efficacy in clinical dental / oral care. You can, Kit.

33. A kit according to any one of claims 29 to 32, for monitoring the progress of a treatment. The sensor may further include a sensor capable of detecting the progress of the treatment, in particular A control signal can be generated based on the progress of the treatment, the control signal being coupled to the optoelectronic device. The sensor adjusts the light emitted from the optoelectronic device in response to the adjustment signal. Save money, kit.

34. The shape of a toothbrush or a mouthpiece that can be inserted in the mouth between the biting surfaces of the teeth The present invention relates to a photoelectric device having a shape of a bar-shaped lighting fixture. The kit described.

35. The optoelectronic devices used are microspectrometer sensors, temperature sensors, optical A sensor, a pH sensor, a force sensor, a gyroscope, a pressure sensor or a combination thereof. The kit according to any one of claims 29 to 34, comprising:

36. Tooth whitening material that can be used with a dual wavelength light source or with a photosensitizer - Patents.com The kit according to any one of claims 29 to 35, comprising:

37. A method comprising the steps of: (a) administering a photosensitizer in the form of a water-soluble effervescent tablet; and (b) releasing dual light photons. The kit of any one of claims 29 to 36, comprising a handheld light irradiator.

38. The photosensitizer is in the form of a water-soluble effervescent tablet, gel or paste, and is for one-time use only. The kit according to any one of claims 29 to 37, comprising a mouthpiece and a light irradiator.

39. The photosensitizer was determined to be a photosensitizer that was either introduced or naturally present in the berry extract mouthwash. The kit according to any one of claims 29 to 38, comprising the compound in the form

40. A kit according to any one of claims 29 to 39, comprising hydrogen peroxide as an enhancing compound. 。

41. The optoelectronic device converts light, particularly non-coherent radiation, into a first wavelength of 400 to 430 nm. In terms of wavelength, preferably 1 to 120 J / cm ２ In particular, the irradiation amount is about 10 to about 2500 mW / cm ２ At a power density of 0.5 seconds to 120 minutes and a second wavelength of 780 to 830 nm, Preferably, 1 to 120 J / cm ２ In particular, the irradiation amount is about 10 to about 2500 mW / cm ２ Power The composition according to any one of claims 29 to 40, which can be released at a density of from 0.5 seconds to 120 minutes. The kit described.

42. 3. The optoelectronic device of claim 2, wherein the optoelectronic device comprises a light emitting diode or diodes as a light source.

41. The kit according to any one of claims 9 to 40.

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