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      ANTIBACTERIAL ORAL COMPOSITIONThis document describes the use of photoactivated compositions for disinfection and / or oral treatments that comprise at least one oxidizer, at least one photoactivator capable of activating the oxidizer and at least one curative factor chosen from hyaluronic acid, glucosamine and allantoin, in association with a pharmacologically acceptable carrier.
    公开号:BR112012001016A2
    申请号:R112012001016-6
    申请日:2010-07-19
    公开日:2020-10-27
    发明作者:Remigio Piergallini；Nikolaos Loupis
    申请人:Klox Technologies Inc.；
    IPC主号:
    专利说明:

    “ANTIBACTERIAL ORAL COMPOSITION”
    TECHNICAL FIELD This description refers to the field of antibacterial periodontal composition and the method of total disinfection of the mouth and periodontal treatment with the aid of photodynamic therapy.
    BACKGROUND OF THE INVENTION The main objective of periodontal treatment is to control periodontal infection by altering or eliminating the microbial etiology and contributing factors.
    To date, there is considerable evidence to support scaling and root planing (SRP) as one of the most effective procedures for the treatment of infectious periodontal diseases.
    Treatment strategies used for periodontal treatment include total mouth disinfection, although there is only a minor additive effect compared to conventional SRP.
    There is a general consensus that SRP, in addition to improving clinical parameters, reduces microbial load and results in a shift towards a healthier compatible microflora.
    However, there are conflicting reports about the ability of SRP to eradicate or completely suppress important periodontal pathogens.
    SUMMARY OF THE INVENTION According to one embodiment, a use of a photoactivated composition is disclosed for the manufacture of a medicament for oral disinfection and / or the treatment of an oral disease, the composition containing at least one oxidizer, at least one photoactivator able to activate the oxidizer; and at least one curative factor chosen from hyaluronic acid, glucosamine and allantoin, in association with a pharmacologically acceptable carrier.
    According to one modality, the use of a photoactivated composition for oral disinfection, treatment of an oral disease and favoring the cure of the disease, and / or treatment of periodontitis, the composition containing at least one oxidant, is disclosed; at least a photoactivator capable of activating the oxidizer; and at least one curative factor chosen from hyaluronic acid, glucosamine and allantoin; in association with a pharmacologically acceptable carrier.
    Oral disease can be chosen from gingivitis, periodontitis, periodontal disease, oral thrush, lichen planus and stomatitis.
    Oxidizers can be chosen from hydrogen peroxide, carbamide peroxide, acid peroxide, alkali metal percarbonate and benzoyl peroxide. Preferred oxidizers are hydrogen peroxide and carbamide peroxide, and a combination thereof.
    The antibacterial periodontal composition may further comprise at least one hydrophilic gelling agent.
    The hydrophilic gelling agent can be chosen from glucose, modified starch, methyl cellulose, carboxymethyl cellulose, propyl cellulose, hydroxypropyl cellulose, carbopol polymers, alginic acid, sodium alginate, potassium alginate, ammonium alginate, alginate- calcium, agar, carrageenan, locust bean gum, pectin, gelatin.
    Photoactivators can be chosen from a dye derived from xanthone, an azo dye, a biological paint and a carotenoid.
    The dye derived from xanthene can be chosen from a fluorine dye, a fluorone dye and a rhodol dye.
    The fluorene dye can be chosen from a pyronin dye and a rhodamine dye.
    The pyronin dye can be chosen from pyronin Y and pyronin B.
    The rhodamine dye can be chosen from rhodamine B, rhodamine G and rhodamine WT.
    The fluorone dye can be chosen from fluorescein and fluorescein derivatives.
    The fluorescein derivative can be chosen from phloxin B, cane rose and merbromine.
    The fluorescein derivative can be chosen from eosin Y, eosin B and erythrosine B. Preferably, the fluorescein derivative is eosin Y.
    The azo dye can be chosen from methyl violet, neutral red, para-red, amaranth, carmosin, allura AC red, tartrazine, orange G, ponceau 4R, methyl red and ammonium murexide-purpurate.
    The biological ink can be chosen from safranin O, basic fuchsin, acid fuscine, 3.3 'dihexylocarbocyanine iodide, carminic acid and green indocyanine.
    Carotenoid can be chosen from crocetin, a-crocine (8,8-diapo-8,8-carotenoic acid), zeaxanthin, lycopene, a-carotene, B-carotene, bixin and fucoxanthin.
    Carotenoid may be present in the composition as a mixture chosen from the reddish powder obtained from saffron, annatto extract and brown algae extract.
    The antibacterial periodontal composition may further comprise at least one chelating agent.
    The chelating agent can be chosen from ethylene diaminetetraacetic acid (EDTA) and ethylene glycoltetraacetic acid (EGTA).
    In accordance with one modality, a method of total disinfection of the mouth and / or oral treatment with the aid of photodynamic therapy of a patient, who has the steps of:
    a) apply to a patient's mouth a composition containing at least one oxidizer, at least one photoactivator capable of activating the oxidizer; and at least one curative factor chosen from hyaluronic acid, glucosamine and allantoin; and b) treating said mouth of step a) with actinic light for a time sufficient for the photo-activator to cause the activation of said oxidizer.
    Oral treatment can be for the treatment of an oral disease, and the disease can be gingivitis, periodontitis, periodontal disease, oral thrush, lichen planus, stomatitis, herpes simplex injury, oral mucositis, oral ulcers, oral submucosal fibrosis and glossitis.
    The method of total mouth disinfection and oral treatment with the aid of photodynamic therapy may include exposing the mouth to actinic light for less than about 5 minutes, or for about 60 seconds to about 5 minutes. - tos.
    The method of total disinfection of the mouth and oral treatment with the aid of photodynamic therapy may include exposing the mouth to actinic light for a period shorter than —for about 5 minutes, or for a period of about 60 seconds to about 5 minutes. per cm of an area to be treated.
    The method of total disinfection of the mouth and oral treatment with the aid of photodynamic therapy may include exposing the mouth to an actinic light source that is over the area being treated.
    The method of total disinfection of the mouth and treatment of oral disease with the aid of photodynamic therapy may include applying the composition to a gum, at least close to a tooth, and at least one tooth, and at least one tooth is exposed to actinic light. for a period of about at least 10 seconds on a vestibular side, and about at least 10 seconds on an oral side.
    The method of total mouth disinfection and oral treatment with the aid of photodynamic therapy may include exposing the mouth to actinic light, which can be visible light having a wavelength between about 400 nm and about 700 nm, or about 400 nm and about 600 nm and, preferably, about 450 nm and about 700 nm.
    Oxidizers can be chosen from hydrogen peroxide, carbamide peroxide and benzoyl peroxide.
    The antibacterial periodontal composition may further comprise at least one hydrophilic gelling agent.
    The hydrophilic gelling agent can be chosen from glucose, modified starch, methyl cellulose, carboxymethyl cellulose, propyl cellulose, hydroxypropyl cellulose, polymers - carbopolº, alginic acid, sodium alginate, potassium alginate, ammonium alginate, algine - calcium, agar, carrageenan, locust bean gum, pectin, gelatin.
    Photoactivators can be chosen from a dye derived from xante-
    no, an azo dye, a biological ink and a carotenoid.
    The dye derived from xanthene can be chosen from a fluorine dye, a fluorone dye and a rhodol dye.
    The fluorene dye can be chosen from a pyronin dye and a rhodamine dye.
    The pyronin dye can be chosen from pyronin Y and pyronin B.
    The rhodamine dye can be chosen from rhodamine B, rhodamine G and rhodamine WT.
    The fluorone dye can be chosen from fluorescein and fluorescein derivatives.
    The fluorescein derivative can be chosen from phloxin B, cane rose and merbromine.
    The fluorescein derivative can be chosen from eosin Y, eosin B and erythrosine B.
    The azo dye can be chosen from methyl violet, neutral red, para-red, amaranth, carmosin, allura AC red, tartrazine, orange G, ponceau 4R, methyl red and ammonium murexide-purpurate.
    The biological ink can be chosen from safranin O, basic fuchsin, acid fuscine, 3.3 'dihexylocarbocyanine iodide, carminic acid and green indocyanine.
    Carotenoid can be chosen from crocetin, a-crocine (8,8-diapo-8,8-carotenoic acid), zeaxanthin, lycopene, a-carotene, B-carotene, bixin and fucoxanthin.
    Carotenoid can be present in the composition as a mixture chosen from reddish powder obtained from turmeric, annatto extract and brown algae extract. The antibacterial periodontal composition may further comprise at least one chelating agent.
    The chelating agent can be chosen from ethylene diaminetetraacetic acid (EDTA) and ethylene glycoltetraacetic acid (EGTA).
    The following terms are defined below.
    The term "hydrophilic gelling agent" is intended to mean a material that thickens and stabilizes liquid solutions, emulsions and suspensions. Hydrophilic freezing agents dissolve in liquid and provide a structure that gives the resulting gel an appearance of a solid matter, although, in most cases, it is composed of a liquid. Hydrophilic freezing agents are very similar to thickeners.
    The term “actinic light” is intended to mean light energy emitted from a specific light source (lamp, LED or laser) and capable of being absorbed by matter (for example, the photoactivator defined below) and producing an identifiable change or measurable when one interacts with the other. As a clinically identifiable change,
    presume a change in the color of the photoactivator used (for example, from red to transparent).
    The term “photoactivator” is intended to mean a chemical compound capable of absorbing actinic light. The photoactivator easily undergoes photoexcitation and then transfers its energy to other molecules, thereby enhancing or accelerating the dispersion of light and enhancing or activating the oxidant present in the reaction mixture.
    The term “oxidizer” is intended to mean a chemical compound that easily transfers oxygen atoms and oxidizes other compounds or a substance that gains electrons in a chemical redox reaction.
    The term “chelating agent” is intended to mean a chemical that removes metal ions, such as iron, and keeps them in solution.
    The term "curative factor" is intended to mean a compound that promotes or enhances the healing or regenerative process of a tissue.
    The term "time of exposure to actinic light" is intended to mean the time when a tissue, skin or wound is exposed to actinic light by applying actinic light.
    The term “total exposure time to actinic light” is intended to mean the cumulative time when a tissue, skin or wound is exposed to actinic light after several applications of actinic light.
    The term "pharmacologically acceptable carrier" is intended to mean a preservative solution, a saline solution, an isotonic saline solution (about 0.9%) or about 5% albumin solution, suspension, sterile water, buffered saline with phosphate and the like. Other buffering agents, dispersing agents and non-toxic inert substances suitable for delivery to a patient can be included in the compositions of the present invention. The compositions can be solutions, suspensions or any formulation suitable for administration, and are typically sterile and free of unwanted particulate matter. The compositions can be sterilized by conventional sterilization techniques.
    The term "active oxygen species" is intended to mean chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. They can be inorganic or organic. Active oxygen species are highly reactive, due to the presence of unpaired valence electrons. They are also referred to as "reactive oxygen", "active oxygen" or "reactive oxygen species".
    The term “mouth” is intended to mean the complete oral cavity, which includes the lips, gums, the hard and soft palate, the uvula, tonsils, the teeth, the inside of the mouthpieces, the lingual papillae of the tongue.
    The term "periodontal pocket" is intended to mean the presence of an abnormally deep gingival sulcus as it contacts a tooth. The gingival sulcus (root
    nhura) is the potential space between a tooth and the adjacent gingival tissue and is lined by the sulcular epithelium. The depth of the groove is delimited by two entities: apically by the gingival fibers of the connective tissue fixation and coronarily by the free gingival margin. When the sulcular depth is in excess of three millimeters on a constant basis, even regular toothbrushing will be unable to properly clean the bottom of the groove, allowing food and microbial debris to accumulate and pose a danger to the fibers of the periodontal ligament that fix the tooth to the gum. If left to remain for a long time, these microbes, together with the enzymatic particles they produce, will be able to penetrate and ultimately destroy the delicate soft tissue and fibers of periodontal fixation, leading to yet another deepening of the groove ( plus three millimeters), resulting in a periodontal pocket.
    Characteristics and advantages of the subject matter of this report will become more evident in light of the following detailed description of selected modalities, as shown in the attached figures. As will be understood, the object material disclosed and claimed can be modified in several aspects, without departing from the scope of the claims. Consequently, the drawings and the description should be considered illustrative in nature, and not restrictive, and the full scope of the subject matter is presented in the claims.
    BRIEF DESCRIPTION OF THE DRAWINGS Other characteristics and advantages of the present disclosure will become evident from the following detailed description, taken in combination with the accompanying drawings, in which: Fig. 1A is a figure illustrating a periodontitis in a patient be treated with a method according to an embodiment of the present invention.
    Fig. 18 is a figure illustrating periodontitis in a patient to be treated with a method, according to an embodiment of the present invention.
    Fig. 1C is a figure illustrating a periodontitis in a patient to be treated with a method, according to an embodiment of the present invention.
    Fig. 2A is a figure illustrating periodontitis in a patient to be treated - with a method, according to an embodiment of the present invention.
    Fig. 2B is a figure illustrating periodontitis in a patient being treated with a composition, according to an embodiment of the method of the present invention.
    Fig. 2C is a figure illustrating periodontitis in a patient being treated with a composition, according to an embodiment of the method of the present invention.
    Fig. 2D is a figure illustrating periodontitis in a patient treated with a composition, according to an embodiment of the method of the present invention.
    Fig. 3A is a figure that illustrates a patient's mouth and teeth two weeks
    after being treated with a composition, according to an embodiment of the method of the present invention.
    Fig. 3B is a figure illustrating the depth of a periodontal pocket in a patient's mouth two weeks after being treated with a composition, according to one embodiment of the method of the present invention.
    Fig. 3C is a figure illustrating the depth of a periodontal pocket in a patient's mouth two weeks after being treated with a composition, according to an embodiment of the method of the present invention.
    Fig. 4A is a figure showing a patient's mouth and teeth six weeks after being treated with a composition, according to an embodiment of the method of the present invention.
    Fig. 4B is a figure showing a patient's mouth and teeth six weeks after being treated with a composition, according to an embodiment of the method of the present invention.
    Fig. 4C is a figure showing a patient's mouth and teeth six weeks after being treated with a composition, according to an embodiment of the method of the present invention.
    Fig. 4D is a figure illustrating the depth of a periodontal pocket in a patient's mouth six weeks after being treated with a composition, according to one embodiment of the method of the present invention.
    Fig. 5A is a figure that illustrates a dental socket from which a tooth was extracted.
    Fig. 58 is a figure illustrating the dental socket during treatment with a composition, according to an embodiment of the method of the present invention.
    Fig. 5C is a picture of the dental bag 24 hours after treatment with the composition, according to an embodiment of the method, according to the present invention.
    DETAILED DESCRIPTION According to one embodiment, a use of a photoactive composition is provided for the manufacture of a medicament for oral disinfection and / or the treatment of an oral disease, wherein the composition comprises: and at least one oxidizer, and at least one photoactivator capable of activating the oxidizer; and and at least one curative factor chosen from hyaluronic acid, glucosamine and allantoin, in association with a pharmacologically acceptable carrier.
    According to another embodiment, a use of a photoactivated composition for oral disinfection is provided, wherein the composition comprises:
    and at least one oxidizer; and at least one photoactivator capable of activating the oxidizer; and and at least one curative factor chosen from hyaluronic acid, glucosamine and allantoin; in association with a pharmacologically acceptable carrier.
    According to another embodiment, a use of a photoactivated composition is provided for the treatment of an oral disease, wherein the composition comprises: and at least one oxidant; and at least one photoactivator capable of activating the oxidizer; and and at least one curative factor chosen from hyaluronic acid, glucosamine and allantoin; in association with a pharmacologically acceptable carrier.
    According to another embodiment, a use of a photoactivated composition is provided for the treatment of periodontitis, wherein said composition comprises: and at least one oxidant; and at least one photoactivator capable of activating the oxidizer; and and at least one curative factor chosen from hyaluronic acid, glucosamine and allantoin; in association with a pharmacologically acceptable carrier.
    According to another modality, a method of total disinfection of the mouth and oral treatment with the aid of photodynamic therapy of a patient is provided, which comprises the steps of: a) applying to a patient's mouth a composition comprising at least one oxidizer , at least one photoactivator capable of activating the oxidizer; and at least one curative factor chosen from hyaluronic acid, glucosamine and allantoin; and b) treating said mouth of step a) with actinic light for a time sufficient for said photoactivator to cause the activation of said oxidizer.
    Periodontal diseases caused by bacterial infection can also be treated with the composition of the present invention. Oral diseases, such as gingivitis, periodontitis, periodontal disease, oral thrush, lichen planus and stomatitis can also be treated with the composition.
    The composition comprises several active ingredients selected from groups of possible components. These various active principles have their mechanism of action. Oxidizers The composition comprises oxidants as a source of oxygen radicals. Peroxide compounds are oxidizers that contain the peroxy group (R-O-O-R), which is a chain-like structure containing two oxygen atoms, each of which is linked to the other and to a radical or some element. Suitable oxidizers for the preparation of the active medium include, but are not limited to: Hydrogen peroxide (H2O> 2) is the starting material for preparing organic peroxides. H2O> r is a potent oxidizing agent and the unique property of hydrogen peroxide is that it breaks down into water and oxygen and does not form any persistent or toxic residual compound. Hydrogen peroxide for use in this composition can be used in a gel, for example, with 6% hydrogen peroxide. A suitable concentration range over which hydrogen peroxide can be used in the present composition is less than about 12%, or about 1% to about 12%, preferably about 3.5 % to about 12% 'and, more preferably, from about 3.5% to about 6%.
    Urea hydrogen peroxide (also known as urea peroxide, carbamide peroxide or percarbamide) is soluble in water and contains approximately 36% hydrogen peroxide. Carbamide peroxide for use in this composition can be used as a gel, for example, with 16% carbamide peroxide which represents 5.6% hydrogen peroxide. A suitable concentration range over which urea peroxide can be used in the present composition is less than 36%, or from about 3% to about 36%, and preferably from about 10% to about 36% and, more preferably, from about 3% to about 16%. Urea peroxide breaks down into urea and hydrogen peroxide in a slow-release form that can be accelerated with heat or photochemical reactions. Released urea [carbamide, (NH2) CO>)], is highly soluble in water and is a potent protein denaturant. It increases the solubility of some proteins and accentuates the rehydration of the skin and / or mucosa.
    Benzoyl peroxide consists of two benzoyl groups (benzoic acid with the H of the carboxylic acid removed) joined by a peroxide group. It is found in paraacne treatments, in concentrations ranging from 2.5% to 10%. The released peroxide groups are effective in killing bacteria. Benzoyl peroxide also promotes skin modification and pore whitening, which further helps to decrease bacterial counts and reduce acne. Benzoyl peroxide breaks down into benzoic acid and oxygen in contact with the skin and is non-toxic. A suitable concentration range over which benzoyl peroxide can be used in the present composition is less than about 10%, or from about 1% to about 10%, or, preferably, from about 1% to about from 8%, and more preferably from about 2.5% to about 5%.
    Suitable oxidizers may also include peroxy acids and alkali metal percarbonates, but the inclusion of other forms of peroxides (eg, organic or inorganic peroxides) should be avoided due to their increased toxicity and their unpredictable reaction with photodynamic energy transfer.
    Photoactivators
    Photoactivators transfer light energy to oxidants. Suitable photoactivators can be fluorescent dyes (or dyes), although other groups of dye or dyes (biological and histological dyes, food dyes, carotenoids) can also be used. Combination photoactivators can increase photoabsorption through the combined dye molecules and enhance the absorption and selectivity of photobiomodulation. This creates multiple possibilities for generating new mixtures of photosensitive and / or selective photoactivators.
    An advantageous feature of a photoactivator is the increased fluorescence. In the present invention, the re-emission of light in the green to yellow spectrum would be advantageous, since it is a deep penetrating wavelength band, with deep absorption by blood. This results in a strong increase in blood flow, vasodilation and angiokinetic phenomena. Suitable photoactivators include, but are not limited to: Xanthene derivatives Xanthene-derived dyes have been used and tested for a long time all over the world. They exhibit low toxicity and increased fluorescence. The xanthene group consists of 3 subgroups which are: a) fluorenes; b) fluorones; and c) the wheels.
    The fluorene group comprises pyronins (for example, pyronin Y and B) and rodendins (for example, rhodamine B, G and WT). Depending on the concentration used, pyroins and rhodamine can be toxic and their interaction with light can lead to increased toxicity. Similar effects can occur for the rhodol dye group.
    The fluorone group comprises fluorescein dye and fluorescein derivatives.
    Fluorescein is a fluorophore commonly used in microscopy with a maximum absorption of 494 nm and a maximum emission of 521 nm. The fluorescein disodium salt is known as D&C Yellow 8. It has a very high fluorescence, but it photodegrades very quickly. In the present composition, mixtures of fluorescein with other photoactivators, such as green indocyanine and / or reddish powder obtained from saffron, will provide increased photoabsorption to these other compounds.
    The eosin group comprises Eosin Y (tetrabromofluorescein, red acid 87, D&C Red 22) with a maximum absorption of 514 to 518nm, pigments of cell cytoplasm, collagen, muscle fibers and red blood cells; and Eosin B (red acid 91, scarlet eosin, dibromo dinitrofluorescein), with the same pigmentation characteristics of Eosin Y. Eosin Y and eosin B are collectively referred to as “Eosin”, and use of the term “Eosin” if refers to Eosin Y, Eosin B or one mixed two. Eosin Y, Eosin B or a mixture of the two can be used, due to their sensitivity to the light spectra used: broad spectrum of blue light, blue to green light and green light. Its pigmentation properties of tissue and bio-film and its low toxicity
    de are also advantageous.
    Eosin Y and Eosin B pigment red blood cells and, thus, provide the composition of the present invention with hemostatic properties (control of the flow or stopping of blood flow), as well as increasing the selective targeting of light to the soft tissues of the lesion. or injury during application of the composition.
    In some embodiments, the composition includes in the range of less than about 12% of at least one between Eosin B or Eosin Y or combinations thereof, or from about 0.02% to about 12% of at least one between Eosin B or Eosin Y or combinations thereof, or between about 0.02% and about 1.2%, or about 0.02% to about 0.5%, or about 0.5% to about 0.8% of at least one between Eosin B or EosineY or combinations thereof.
    In yet another embodiment, the composition includes less than 12% of at least one between Eosin B or Eosin Y or combinations thereof, or from about 0.02% to about 12% of at least one between Eosin B or Eosin Y or combinations thereof, or between about 0.02% and about 1.2%, or from about 0.02% to about 0.5%, or from about 0.02% to about less than 0.5% or about 0.5% to about 0.8% of at least one between Eosin B or Eosin Y or combinations thereof, and / or less than about 2% Erythrosine B, or about 0.005 to about 2% Erythrosine B, or about 0.005% to about 1%, or about 0.01% to about 1%, or about 0.005% and about 0.15% Erythrosine B.
    Phloxin B (2,4,5,7 tetrabromo 4,5,6,7, tetrachlorofluorescein, D&C Red 28, red acid 92) is a fluorescein-derived red dye that is used for wastewater disinfection and detoxification through photo-oxidation.
    It has a maximum absorption of 535 to 548nm.
    It is also used as an intermediary to manufacture photosensitive dyes and drugs.
    Erythrosine B, or simply Erythrosine (red acid 51, tetraiodofluorescein) is a fluorine food coloring based on charcoal, cherry pink, used as a biological paint and an agent that exhibits bio-film and dental plaque, with maximum absorption of 524 at 530 nm in aqueous solution.
    It is subjected to photodegradation.
    Erythrosine is also used in some modalities, due to its photosensitivity to the light spectra used and its ability to pigment biopellicles.
    The inclusion of erythrosine should be favored when using the composition in deep pockets of infected or contaminated tissue, such as periodontal pockets in periodontal therapy.
    In some embodiments, the composition includes in the range of less than about 2% Erythrosine B, or from about 0.005 to about 2% Erythrosine B, or from about 0.005% to about 1%, or about 0.01% to about 1%, or about 0.005% and about 0.15% Erythrosine B.
    Bengal rose (4,5,6,7 tetrachlor 2,4,5,7 tetraiodofluorescein, red acid 94) is a bright bluish-pink biological dye with a maximum absorption of 544 to 549nm, which was used as a dye, biological ink and diagnostic aid.
    Also used in synthetic chemistry to generate singlet from triplet oxygen.
    Merbromine (mercurochrome) is an organomercuric disodium salt of fluorescein with a maximum absorption of 508 nm. It is used as an antiseptic.
    Azo dyes Azo (or diazo) dyes share the N-N group, called azo group. They are used mainly in analytical chemistry or as food colors and are not fluorescent. Suitable azo dyes include: Methyl violet, neutral red, para- red (pigment red 1), amaranth (Azorubin S), Carmosina (Azorubin, food red 3, acid red 14), allura AC red (FD&C 40), tartrazine (FD&C Yellow 5), orange G (acid orange 10), Ponceau 4R (food red 7), methyl red (acid red 2), ammonium purpurate.
    Biological Inks Pigment molecules commonly used in pigmentation protocols for biological materials can also be used as photoactivators. Suitable biological inks - which include: Safranin (Safranin O, basic red 2) is also an azo dye and is used in histology and cytology. It is a classic count ink in a Gram pigmentation protocol.
    Fuchsin (basic or acidic) (rosaniline hydrochloride) is a magenta biological dye that can pigment bacteria and has been used as an antiseptic. It has a maximum absorption of 540 to 555 nm.
    3,3'-dihexylocarbocyanine iodide (DIOC6) is a fluorescent dye used to pigment the endoplasmic reticulum, vesicular membranes and cell mitochondria. It shows photodynamic toxicity when exposed to blue light and has a green fluorescence Carminic acid (acid red 4, natural red 4) is a red glycosidic hydroxyanthrapurine naturally obtained from cochineal insects.
    Green indocyanine (ICG) is used as a diagnostic aid for the determination of blood volume, cardiac output or liver function. ICG binds strongly to red blood cells and when used in combination with fluorescein, increases the absorption of blue to green light.
    Carotenoids Carotenoid dyes can also act as photoactivators.
    The reddish powder obtained from saffron is a compound containing natural carotenoids.
    Saffron is a condiment derived from Crocus sativus. It is characterized by a bitter taste and iodoform or hay-like fragrance. These are caused by the picrocrocina and safranal compounds. It also contains the crocine carotenoid dye that provides its characteristic yellow-red color.
    Saffron contains more than 150 different compounds, many of which are carotenoids: mangicrocin, reaxanthin, lycopene and various a- and B-carotenes, which show satisfactory light absorption and beneficial biological activity. Saffron can also act as a photon transfer agent and a curative factor. The color of saffron is primarily the result of a-crocine (8.8 diapox-8.8-carotenoid acid). The reddish powder obtained from dried saffron is highly sensitive to fluctuating pH levels and quickly breaks down chemically in the presence of light and oxidizing agents. It is more heat resistant. Data show that saffron has anticarcinogenic, immunomodulatory and antioxidant properties.
    For absorbance, it is determined for the chroma-specific photon wavelength of 440 nm (blue light). It has a deep red color and forms crystals with a melting point of 186ºC. When dissolved in water, it forms an orange solution.
    Crocetin is another compound of turmeric that has been discovered to express an antilipidemic action and promote oxygen penetration into different tissues. More specifically, increased oxygenation of capillary endothelial cells was observed. An increase in oxygenation of muscles and cerebral cortex was observed and led to an increased survival rate in laboratory animals with induced hemorrhagic shock or emphysema.
    Anato, a condiment, contains as a main constituent (70 to 80%) the carotenoid of bixin which exhibited relevant antioxidative properties.
    B-carotene also exhibited adequate characteristics.
    Fucoxanthin is a constituent of brown algae with a considerable capacity for photosensitizing redox reactions.
    Curative Factors Curative factors comprise compounds that promote or enhance the healing or regenerative process of tissues at the site of application of the composition. During photoactivation of the composition, there is an increase in the absorption of molecules at the treatment site through the skin or mucosa. An increase in blood flow at the treatment site is observed over a period of time. An increase in lymphatic drainage and a possible change in osmotic balance, due to the dynamic interaction of free radical cascades, can be accentuated or even strengthened with the inclusion of curative factors. Suitable curative factors include, but are not limited to: Hyaluronic acid (Hyaluronan, hyaluronate): it is an unsulfated glycosaminoglycan, widely distributed throughout the connective, epithelial and neural tissue. It is one of the main components of the extracellular matrix and contributes significantly to cell proliferation and migration. Hyaluronan is a major component of the skin, where it is involved in tissue repair. Although it is abundant in extracellular matrices, it contributes to
    tissue dynamics, cell movement and proliferation and participates in a wide number of cell surface receptor interactions, notably those including the primary CD44 receptor. Hyaluronidase enzymes degrade hyaluronan.
    There are at least seven types of hyaluronidase enzymes in humans, several of which are tumor suppressors.
    The degradation products of hyaluronic acid, oligosaccharides and hyaluronic acid of very low molecular weight, exhibited pro-angiogenic properties.
    Furthermore, recent studies have shown that fragments of hyaluronan, but not the native high molecular weight mass of hyaluronan, can induce inflammatory responses in macrophages and dendritic cells in tissue damage.
    Hyaluronic acid is well suited to biological applications that target the skin.
    Due to its high biocompatibility, it is used to stimulate tissue regeneration.
    Current studies have shown the appearance of hyaluronic acid in the early stages of healing to create a physical environment for the white blood cells that mediate the immune response.
    It is used in the synthesis of biological scaffolding for wound healing applications and in treatment against wrinkles.
    In one embodiment, the composition includes in the range of less than about 2% hyaluronic acid, or from about 0.001% to about 2%, or, preferably, from about 0.002% to about 2%, or about 0.002% to about 1% hyaluronic acid.
    Glycosamine: is one of the most abundant monosaccharides in human tissues and a precursor in the biological synthesis of glycosylated proteins and lipids.
    It is commonly used - osteoarthritis treatment.
    The common form of glucosamine used is its sulfate salt.
    Glycosamine shows several effects, including anti-inflammatory activity, stimulating the synthesis of proteoglycans and the synthesis of proteolytic enzymes.
    A suitable concentration range over which glycosamine can be used in the present composition is less than about 5%, or from about 0.0001% to about 5%, or about 0.0001% at about 3%, and preferably about 0.001% to about 3%, or about 0.011% to about 1% and about 1% to about 3%. Allantoin: is a glyoxylic acid diureide.
    It has a keratolytic effect, increases the water content of the extracellular matrix, accentuates the flaking of the upper layers of dead skin cells (apoptotic) and promotes skin proliferation and wound healing.
    In one embodiment, the composition includes in the range of less than about 1% allantoin, or from about 0.001% to about 1%, or from about 0.002% to about 1%, or, preferably, from about 0.02% to about 1%, and, more preferably, from about 0.02% to about 0.5%. In addition, saffron can act as a photon transfer agent and a healing factor.
    Chelating Agents Chelating agents can be included to promote removal of the stained layer in closed infected pouches and difficult to reach lesions; acts as a metal ion extinguisher and as a buffer. Suitable chelating agents include, but are not limited to: Ethylene-diamino-tetra-acetic acid (EDTA): It is an amino acid used for di- and trivalent metal sequestrions. EDTA binds to metals through 4 carboxylate groups and 2 amine groups. EDTA forms especially strong complexes with Mn (Il!), Fe (lll), Cu (lll) and Co (ll!). Prevents platelet collection and blood clot formation. It is used in endodontic therapy as an agent to remove the stained layer during instrumentation. It is used in buffer solutions.
    Ethylene glycolic acid! tetraacetic (EGTA) is related to EDTA, but with a much higher affinity for calcium ions than for magnesium ions. It is useful for making buffer solutions that resemble the medium within living cells and is often used in dentistry, more specifically in endodontics, to remove stained layers.
    Hydrophilic Freezing Agents The antibacterial periodontal composition may also contain one or more hydrophilic freezing agents. The hydrophilic gelling agent accentuates the consistency of the composition and contributes to facilitate the application of the composition on the skin or injured area. In addition, when used with hydrogen peroxide (H2O> 2), it can contribute to the reduction of H2O release, and provide a more immediate reaction, as pure H2O2 can be used directly. Suitable hydrophilic freezing agents include, but are not limited to, glucose, modified starch, methylcellulose, carboxymethylcellulose, propylcellulose, hydroxypropylcellulose, Carbopolº polymers, alginic acid, sodium alginate, potassium alginate, ammonium alginate, calcium alginate, agar, carrageenan , locust bean gum, pectin and gelatin.
    Photoactivation The inclusion of suitable photosensitive compounds and activation with a source of an appropriate wavelength leads to acceleration in the processes of breaking down the source of peroxide (the oxidizer) and the other reactions that occur, through a photodynamic phenomenon. The photosensitive compounds included are illuminated by photons of a certain wavelength and excited in a greater state of energy. When the electrons excited by photoactivators return to a lower state of energy, they emit photons with a lower level of energy, thereby causing the emission of light of a longer wavelength (Stokes displacement). In the appropriate medium, much of this energy transfer is transferred to reactive oxygen or hydrogen peroxide and causes the formation of active oxygen species, such as singlet oxygen and other active oxygen.
    Singlet oxygen and other reactive oxygen species generated by activating the composition can operate in a hormone form. That is, a beneficial health effect is achieved by low exposure to a normally toxic stimulus (eg, reactive oxygen), stimulating and modulating stress response pathways in targeted tissue cells. The endogenous response to the generated exogenous free radicals (reactive oxygen species) is modulated in an increased defense capacity against exogenous free radicals and induces acceleration of healing and regenerative processes. In addition, activating the composition will also produce an antibacterial effect. The extreme sensitivity of bacteria to exposure to free radicals makes the composition of the present invention a de facto bactericidal composition.
    The possible mechanism of action must be a phenomenon of fortified redox signaling resulting in the process of marked signal transduction in which the cells convert one type of signal to another; the activated “second messengers” induce a “signal chaser” starting with a relatively small stimulus that evokes a wide response through biologically monitored amplification of such signals. These complex mechanisms possibly work involving angiogenic phenomena through the activation of the growth factor.
    This method can be described as a form of photodynamic therapy. However, unlike other photodynamic techniques, where photoactivators are incorporated into the tissue structure, in the present method, the photoactive material is in simple contact with the tissue and acts when activated by light, as a “photodynamic device” that interacts chemically with the tissue. In addition, actinic light penetrates the tissue and the light that is emitted by the photoactivator (light of a longer wavelength) is also absorbed by the tissue.
    Any actinic light source can be used. Any type of halogen lamp, LED or plasma arc, or laser can be suitable. The main characteristic of suitable sources of actinic light will be that they emit light at a wavelength (or wavelengths) appropriate to activate one or more photoactivators present in the composition. In one embodiment, an argon laser is used. In another embodiment, a potassium-titanyl phosphate (KTP) laser (for example, a GreenLight "Y" laser) is used. In yet another modality, an LED photo-curing device is the current light source. In yet another embodiment, the actinic light source is a visible light source having a wavelength between 400 and 700 nm, and preferably between 400 and 600 nm, and more preferably between 450 and 700 nm . In addition, the actinic light source must have an adequate power density. The power density suitable for non-collimated light sources (LED, halogen or plasma lamps) is in the range of about 800 —mW / cm About 3000 mW / cm , and preferably around 900 mW / cm at about 2000 mW / cm . Is the power density suitable for laser light sources in the range of about 0.5 mW / cm at about 0.8 mW / cm .
    The duration of exposure to actinic light will depend on the surface of the treated area, and the type of injury or trauma being treated. The photoactivation of the composition can occur within seconds or fragments of seconds, but a prolonged exposure period is beneficial to explore the synergistic effects of the absorbed light, reflected in the composition of the present invention and its interaction with the tissue under - treatment. In one embodiment, the time of exposure to actinic light of the tissue in which the antibacterial periodontal composition was applied is a period of less than 5 minutes. In another embodiment, the exposure time is about 20 seconds to about 5 minutes, or between about 60 seconds to about 5 minutes. In another mode, the time of exposure to the actinic light of the tissue in which the antibacterial periodontal composition was applied is a period shorter than about 5 minutes. In another mode, is the exposure time between about 20 seconds to about 5 minutes, or between about 60 seconds and about 5 minutes per cm of the area under treatment, so that the total exposure time of an area of 10 cm between 10 minutes and 50 minutes. In yet another modality, the actinic light source is in continuous movement over the treated area during the appropriate exposure time. In yet another mode, multiple applications of the antibacterial periodontal composition and actinic light are performed. In some modalities, the tissue, skin or wound is exposed to actinic light at least two, three, four, five or six times, or more, depending on the patient's requirement. In addition, the complete treatment can be repeated in its entirety, as may be required by the patient. In some embodiments, a fresh application of the antibacterial periodontal composition is applied before exposure to actinic light.
    Oral Diseases The present invention can be used to treat, or at least participate in the treatment of, various oral diseases. Such oral diseases include, but are not limited to: Gingivitis Gingivitis is a disorder that is defined by inflammation of the gums and is characterized as a periodontal disease, which is characterized by the destruction of the gums, tissue, dental alveoli and ligaments that create the structure that holds the teeth in place. Gingivitis is one of the first stages of a serious periodontal disease.
    Symptoms of gingivitis include swollen gums, sores in the mouth, a bright red or purple appearance in the gums, shiny gums, gums that are painless, except when touched, and bleeding gums. Often, the first signs of gingivitis show no symptoms, except for visual symptoms, and probably - they should only be diagnosed by a dental professional. Periodontal disease Periodontal disease is also known as trench mouth. The peri-
    odontal leads to severe gingivitis and can cause bleeding gums, suppuration, is highly painful and often leads to premature tooth loss. Although most developed nations have few cases of periodontal disease, it still simply exists due to the high number of American workers who do not have dental insurance as part of their benefits package. Dental treatment is very expensive and not all patients can afford good dental care.
    Periodontal disease is the most prevalent in developing countries and, in most cases, professional cleaning and antibiotics can resolve most cases of periodontal disease. However, if infection is not treated, it can spread throughout the body and can lead to serious health complications.
    Symptoms of periodontal disease include painful gums, bad breath, a bad taste in the mouth, fever, gums that bleed only with mild amounts of pressure, cracks classified as thrush between teeth and gums, swollen lymph nodes around the head , neck or jaw, a gray film on the gums, red gums, —stained gums and pain when eating and swallowing.
    Periodontitis Periodontitis or Pyorrhea alveolaris is the inflammation of the periodontium which comprises tissues that support the teeth in the oral cavity. The parts included in the periodontium are the gum (gum tissue), the alveolar bone that are alveoli where the teeth are fixed, the cementum or outer layer of the tooth roots and the periodontal ligaments or PDL composed of connective tissue fibers connecting the gingiva. and cement to the alveolar bone. The condition is described as the progressive loss of bone around the teeth, leading to loose teeth or loss of teeth if the condition is not treated.
    There are different causes for the disease in which bacteria are the most common.
    Periodontitis is considered an advanced stage of gum disease, as it already involves bone loss in the area. It is the effect of untreated mild gingivitis. Due to the presence of bacterial infection, the body can also respond negatively, leading to other complications. The condition is one of the causes that leads to tooth loss among adults, affecting around 50% of any individuals over 30 years of age.
    Signs and symptoms arise due to the unstable anchorage of the teeth, as well as the presence of microorganisms. Occasionally or frequently, gums bleed or become red during tooth brushing, flossing, biting food, chewing or touching with fingers. Occasionally, the gums also swell or develop pus. The affected individual probably has halitosis or bad breath and a “gostometálico” inside the mouth. Teeth appear longer and sharper due to the gingival recession which can also partially be caused by hard brushing. If enzymes called collagenases start to destroy collagen, the person will have deep pockets between their teeth and gums.
    During the early stages of periodontal disease, only a few signs and symptoms can be noticed. Aggressive periodontitis can affect younger individuals and can occur in episodes. Some episodes can have very mild symptoms, while others can be very severe. The signs and symptoms, especially in the case of chronic periodontitis, are usually progressive in nature.
    Oral cold sore Oral cold sore is the condition where the fungus Candida albicans grows quickly and uncontrollably in the mouth. The bacterium known as flora keeps Canida albicans' growth under control in a healthy body. Oral thrush appears as a creamy white paste that covers the tongue, and can spread quickly to the roof of the mouth, gums, back of the throat, tonsils and the inside of the cheeks. Babies, children, the elderly and patients whose immune systems have been compromised in some way are more likely to exhibit oral thrush.
    The symptoms of oral thrush begin with a white, pasty covering over the tongue and on the inside of the cheeks. As the oral thrush continues to develop, it can cause a mild amount of bleeding if the tongue is brushed or when patients brush their teeth. These symptoms can develop very quickly, but canker sores can last for several months. If lesions from the oral thrush spread to the esophagus, the patient may develop addiction symptoms, such as difficulty swallowing, feeling of food stuck in the throat or in the middle of the chest and fever, if the infection continues to spread. spread after the esophagus.
    Lichen Planus Lichen planus is most often defined as an oral disease that affects the lining of the mouth with inflammation. Lichen planus is most often recognized as an exanthema that irritates tissue in the oral cavity. Most patients present their first case between the ages of 45 and 60, although a slowly increasing number of reports are presented in younger patients. Although lichen planus is more often associated with the inside of the cheeks, many cases show that the entire mouth is affected, including the gums, tongue, lips and, in rare cases, the throat or esophagus. Lichen planus also occurs on the skin, as a skin disease, and often must be specifically referred to as skin lichen planus for differentiation between the oral type.
    Lichen planus is an independent disease that can last for weeks, months and, in some cases, years. It is not contagious. It is often confused with genital diseases, as the genitals are often the most affected during the early stage of development. Because symptoms and outbreaks occur quickly and
    as they disappear, often for weeks, treatment is difficult. Although some patients find great relief in cold compresses or compression stockings and cold baths, most patients require medical treatment in order to relieve their symptoms. Stomatitis Basically, stomatitis means inflammation of the mouth, but more specifically, stomatitis is the inflammation of the mucous lining of the mouth that can include the gums, tongue, cheeks, lips and the floor or roof of the mouth. There are different types of stomatitis and the classification is based on how the disease was acquired by a person. The two types of stomatitis are contact stomatitis and aphthous stomatitis. Contact stomatitis is an inflammation of the oral mucosa caused by contact with allergens or irritants. It is classified by its distribution pattern, etiological factors and clinical characteristics. There are some cases of contact stomatitis that are not detected because of the absence of clinical signs. Any individual can have contact stomatitis, regardless of race, age and sex, although it has been observed that it is more common in the elderly.
    Aphthous stomatitis, also known as a mouth ulcer or aphthous ulcers, has an unknown etiology. Like contact stomatitis, ulcers in the oral membrane affect the oral mucosa. An aphthous ulcer is a type of oral ulcer, which presents as a painful open wound inside the mouth or upper throat (including the uvula) caused by a rupture in the mucous membrane. The condition is also known as Sutton's disease, especially in the case of major, multiple or recurrent ulcers. Ulcers can be described as superficial, discrete and painful and are usually visible on the loose mucous membranes. This type of stomatitis, as well as contact stomatitis, is self-limiting and usually does not cause complications. The normal size of ulcers can last 1 to 2 weeks, but larger ulcers can last months. Herpes simplex lesions Herpes simplex is a viral disease caused by the herpes simplex virus. Both the herpes simplex virus 1 (HSV-1) and the herpes simplex virus 2 (HSV-2) cause simple herpes. Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are commonly called cold sores, and infects the face and mouth. Oral herpes is the most common form of herpes simplex virus infection.
    Other Oral Inflammatory Lesions The present invention can be used to treat other types of oral inflammation, including, but not limited to oral mucositis, oral ulcers caused by infections by viruses, bacteria, fungi or protozoa, or caused by disorders of the immune system (immunodeficiency, autoimmunity or allergy). Also included is oral submucosal fibrosis, a chronic debilitating disease of the oral cavity CHARACTERIZED by inflammation and progressive fibrosis of the tissues of the submucosa. Also included is Glossitis, an inflammation or infection of the tongue. It causes the tongue to swell and change color.
    EXAMPLE | An exemplary antibacterial periodontal composition was prepared by mixing the following components: Table 1 - Exemplary Antibacterial Composition (16%) Eosin Y (0.25%) Hyaluronic acid (3%) Reddish powder obtained from saffron (0, 25% The oxidant (4 ml) and curative factors (1.5 ml) were mixed and combined with the photoactivators (1 ml) .The composition was applied to a patient's mouth and activated with actinic light provided by a photocure device with LED (blue light) .The composition was removed after treatment.
    EXAMPLE II A second exemplary antibacterial periodontal composition was prepared by mixing the following components: Table 2 - exemplary antibacterial composition Carbamide peroxide Fluorescein Glucosamine sulfate (3%) Reddish powder obtained from turmeric (0.25% O oxidant (4 mL) and curative factors (1.5 mL) were mixed and combined with the photoactivators (1 mL). The resulting composition was applied to a patient's mouth and activated with actinic light provided by a photocure device with LED (blue light) ) The composition was removed after treatment.
    This second exemplary composition used the fluorescein dye as a photoactivator for other dyes (indocyanine green and reddish powder obtained from saffron) present in the composition. The addition of a small amount of fluorescein to the solution of green indocyanine and reddish powder obtained from saffron caused re-emission of light in wavelengths that activated the other dye compounds and improved the treatment by increasing the absorption criteria / clinical re-emission established.
    Green indocyanine binds satisfactorily to hemoglobin and helps in the absorption of selective energy through the tissues and also helps in targeting these tissues with the generated free radical cascades. In addition, this mixture of photoactivators is able to make the saffron reddish fluorescent, which again improves the phenomena - photodynamics and biostimulants.
    EXAMPLE Ill
    Photodynamic therapy (PDT) has been introduced as a new adjunctive method of antibacterial treatment that can complement conventional treatment. PDT is based on the principle that a photoactivable substance, the photosensitizer, binds to the target cell and can be activated by light of an appropriate wavelength. During this process, free radicals are formed (among them singlet oxygen), which then produce an effect that is toxic to the cell.
    A gel was used comprising photosensitizers with specific absorption in blue to green light (450 to 530), which at the same time are bacterial developers. The substrate after the reaction with biopellicle released curative factors that interfered with the regeneration mechanism of the tissues of the mouth (for example, gingiva, periodontal tissues and oral mucosa). This gel was applied at all stages of treatment, as follows: The first session included meticulous oral hygiene instructions (OHI). Then, the gel was applied in the supragingival scraping, facilitating the separation of calculus and paints, providing light anesthesia and hemorrhage control during this procedure.
    In the second session, the gel was applied during subgingival instrumentation to the entire mouth. Local anesthesia was selectively necessary. SRP was performed until the operator realized that the root surfaces were adequately debrided and flattened. Subsequently, the session was completed using the gel as a photosensitizer that was applied with a blind needle to the instrumented sites starting from the apical end of the pouch and moving coronarily to avoid trapping air bubbles. a 532 nm KTP with 0.7 W power was applied to the bags.
    This new protocol reduced the number of sessions usually required for conventional periodontal treatment; minimized the need for local anesthesia during SRP; the field of operation was clear; patients showed great complacency, clinical parameters were dramatically improved 2 weeks after SRP + PTD.
    EXAMPLE | V Patient Selection Three healthy individuals (mean age 48.6 + 4.2 years), 1 woman and 2 men, 1 smoker formed the test group. The control group comprised 3 healthy individuals (mean age 42.2 + 3.4 years) 1 woman, 2 men, 1 smoker. All individuals showed evidence of Chronic Periodontitis (ChP) and were included in this preliminary study (Table 1).
    All subjects were selected from a private dental clinic limited to periodontics in Piraeus, Greece. All participants gave their consent to participate in the study.
    Periodontal Examination Chronic periodontitis was defined according to the International Classification of
    Periodontal Diseases (Armitage 1999). A complete clinical examination of the mouth was performed by the same examiner calibrated on each patient at the reference value and two points in time before active treatment and two weeks after active periodontal treatment (Table 5), using a manual probe (UNC 15 , Hu Friedy, Chicago, IL, USA). The following parameters were recorded at six sites per tooth, loss of clinical fixation (CAL in mm), bleeding on probing (BOP in percentage of sites) and plaque index (Pl in percentage of sites).
    EXAMPLE V Urea Peroxide Gel The gel comprising photosensitizers (eosin) with specific absorption in blue to green light (450 to 530 nm) that at the same time are bacterial developers capable of revealing bacteria. The base is urea peroxide (CHsN2O3) that releases O, and free radicals after breaking, as well as curative factors that interfere with the tissue regeneration mechanism. Table 3 - Exemplary antibacterial composition Eosin Y carbamide peroxide (0.012%) Glycosamine sulphate Hyaluronic acid (0.02%
    EXAMPLE VI Initial OHI Examination and Supragingival Debridement All patients underwent a hygiene phase with detailed case presentation, supragingival debridement, tooth polishing and repeated oral hygiene instructions. The gel was used as an aid to the supra-gingival debridement procedure only in the test group. Root Scraping / Flattening Two weeks after the initial examination, patients received Scraping / flattening the root of the entire mouth, as follows: Test Group The test group received scraping / flattening of the root of the entire mouth under local anesthesia, as needed, at all sites, exhibiting a PD> 4 mm. SRP was completed within approximately 60 minutes. The gel was used during the mechanical procedure. Freshly sharpened Gracey curettes (Hu-Friedy, Leimen, Germany) and an ultrasonic piezoelectric scraper (Satelecº Suprassonº P-Max Lux, Merignac Cedex - France) were used in combination until the root surface was felt smooth and clean in an exploratory tip (EXD 11/12, Hu-Friedy, Leimen, Germany). Subsequently, the session was concluded using the gel as a photosensitizer that was applied using a device with a blind needle at the instrumented site, which included the periodontal site, starting from the apical end of the bag and moving coro-
    to prevent the trapping of air bubbles. The free gingiva and the part of the tooth root that were related to the periodontal site were also covered with the composition. A 532 nm KTP (Quanta System S.p.A., Solbiate Olona (VA) - Italy) with a power of 0.7 W was applied to the bags (Photodynamic therapy). The laser was adjusted to an irradiation time of 10 seconds. Beginning with the upper jaw, each successive tooth was irradiated for 10 seconds on the buccal side and 10 seconds on the oral side. Control Group The control group received scaling / flattening of the root in the entire mouth by jaw under local anesthesia at all sites, showing a PD> 4 mm. SRP was completed within 60 minutes. Freshly sharpened Gracey curettes (Hu-Friedy, Leimen, Germany) and an ultrasonic piezoelectric scraper (Satelecº Suprassonº P-Max Lux, Merignac Cedex - France) were used in combination until the root surface was perceived smooth and clean in an explorer tip (EXD 11/12, Hu-Friedy, Leimen, Germany). EXAMPLE VII
    RESULTS Patient Characteristics in the Reference Value The characteristics of the reference value of the 6 participants who were treated non-surgically or with the adjunctive use of the gel and photodynamic treatment are shown in Table 4. None of the demographic and periodontal variables seem to show a difference between the two groups. Table 4. Demographic and periodontal variables of patients with Chronic Periodontitis in the reference value Man Average number of sites Numerical data (CAL) were summarized as means and categorical data (BOP and PI) were summarized as frequency distribution (Table 5).
    Both groups showed a significant reduction from the initial examination two weeks after active treatment in all clinical parameters. In the test group, CAL decreased from 5.92 + 1.92 mm at the first visit to 4.38 + 1.69 mm two weeks after treatment (a difference of 1.54 mm). In the control group, CAL decreased from 5.74 + 1.73 mm to 4.94 + 1.92 mm (a difference of 0.8 mm). The difference in BOP percentages in the test group from the reference value two weeks after treatment was 62.42 and in the control group 52.54. The test group showed a tendency to show a greater reduction in CAL and BOP from the initial examination two weeks after active treatment compared to the control group. Table 5. Clinical parameters at reference value and after treatment Test group Control group Sessions 1 2 3 1 2 3 CAL (mm) | 5.92 + 1.92 | 5.44 + 1.62 [4.38 +1.69] 5.74 + 1.73 / 5.31 + 1.94 / 4.94 + 1.92 Average + SD (4.8) (4, 7) (3.5) (4.7) (4.6) (3.5) Min, max BOP (% 79.17 43.53 16.75 73.29 42.29 18.75 PI (%) 65.63 42.31 21.08 60.95 42.18 27.08 Treatment | Initial examination | SRP in the total- Initial examination | SRP in the OHI of the total- OHI + mouth + scraping + scraping | supragingival | Photo-supragingival therapy | Dynamic 48 hours Time- | Reference value | 2 weeks | 2 weeks 2 weeks | 2 weeks training sessions (after exam) after treatment | after treatment initial treatment initial treatment
    EXAMPLE VIII Urea Peroxide Gel The gel comprising photosensitizers (eosin) with specific absorption in blue to green light (450 to 530 nm) that at the same time are bacterial developers capable of revealing bacteria. The base is urea peroxide (CHN2O3) that releases O> and free radicals after breaking, as well as curative factors that interfere with the tissue regeneration mechanism. Table 6 - Exemplary Antibacterial Composition Photoactivators Curative factor (s) Carbamide peroxide Eosin Y (0.012%) Glycosamine sulfate (12%) B (0.01%) Hyaluronic acid (0.02%
    EXAMPLE IX Characteristics of the Patient at the Reference Value The characteristics of the reference value of the 10 participants who were treated non-surgically or with the adjunctive use of the gel and photodynamic treatment are shown in Table 7. None of the demographic and periodontal variables appear to show difference between the two groups . Table 7. Demographic and periodontal variables of patients with Periodontitis.
    Chronic in the reference value Variables Test group | Control group SRP + PDT SRP Age 49.3 + 5.2 46.9 + 4.3 Smoker 2 2 Average number of teeth Plaque (% 61.5 + 3.1 59.7 + 6.8 55.6 + 8 , 1 60.2 + 3.9 Each group of patients was treated, according to the protocol described in Example VI above, numerical data (CAL) were summarized as means and categorical data (BOP and PI) were summarized as frequency distribution (Table 8).
    Both groups showed a significant reduction from the initial examination at six weeks after active treatment in all clinical parameters (See Fig. 4). In the test group, CAL decreased from 5.9 mm at the first visit to 4.3 mm six weeks after treatment (a difference of 1.6 mm). In the control group, CAL decreased from 5.7 mm to 4.5 mm (a difference of 1.2 mm). The difference in BOP percentages in the group detested from the reference value six weeks after treatment was 30.2% in the treatment group and 21.5% in the control group (a difference of 8.7%). The difference in depth of the periodontal pocket (PPD) in the test group from the reference value six weeks after treatment was 2.1 mm, while in the control group it was 1.3 mm (a difference of 8 mm).
    The test group showed a tendency to show a greater reduction in CAL and BOP from the initial examination two weeks after active treatment compared to the control group (See Fig. 3).
    Table 8. CAL, PPD and BOP analysis between SRP and SRP + PDT at the reference value and 6 weeks Es Control group | Test group Variables SRP SRP + PDT CAL (reference value CAL (6 weeks) 4.5 mm PPD (reference value PPD (6 weeks) BOP (reference value 49.7% 51.5% BOP (6 weeks 28 , 2% 21.3% Table 9. Mean differences between SRP and SRP + PDT at the reference value and 6 weeks Variation Control group | Reference group test value - 6 weeks SRP SRP + PDT
    In addition, a visual analog scale (VAS) is used to subjectively measure the patient's pain and discomfort through a continuous sequence of values, ranging from O (no pain) to 10 (unbearable), where values from about 1 to about 3 represent mild pain, values from about 3 to about 7 represent moderate pain, values from about 7 to about 89 represent severe pain and values from about 9 to about 10 represent unbearable pain. The average VAS score for patients who suffered SRP is 2.32, while the patient who suffered SRP with PDT had an average score of 0.52. The protocol for periodontal treatment described in Example VI was applied to patients with chronic periodontitis. During the course of the 6-week period, the patient's periodontitis was healed and completely closed, and they were completely healed, returning their initial wound to its original healthy state.
    EXAMPLE X The exemplary antibacterial periodontal composition of Example VIII was prepared by mixing the following components: the oxidant (4 ml) and curative factors (1.5 ml) were mixed and combined with the photoactivators (1 ml). The resulting composition was pre-illuminated with actinic light provided by an LED photo-curing device (blue light) for less than 5 minutes before application to a patient's mouth. After application, the composition was left in the mouth for less than 5 minutes. The composition was removed after treatment.
    EXAMPLE XI Closing of the Dental Alveolus Now referring to Fig. 5, the tooth of a patient suffering from periodontitis, consecutive abscesses, bone loss and increased tooth mobility, was extracted, leaving an open dental alveolus ( Fig. 5A). The well was cleaned and the antibacterial composition of Example VIII was applied to the well (Fig. 5B), and exposed to actinic light for about 5 minutes. The antibacterial composition was then removed. 24 days after treatment, no blood clot was presented and the newly formed tissue covered the alveolus (Fig. 5C). No sutures were required to promote healing. Such accelerated healing generally does not occur after tooth extraction. The clinical observations from these results can be summarized, as follows: The application of the gel in the initial exam and supragingival scraping emulsify and disperse the formation of the bio-film, facilitating the removal and inks. They also facilitate the removal of hard deposits. The assumption to support the easy removal of hard deposits is the protein breakdown by urea, an organic compound with the chemical formula (NH2) .- CO that is released upon breaking.
    The release of Or causes mechanical disruption of the increments fixed on the surface of the root, as well as a hyperemia in the soft gingival tissues, especially in the epithelium of the pouch, conferring a light anesthesia effect, thus reducing the need for local anesthesia during root scraping / flattening. This also reduces the number of sessions required for subgingival debridement for total mouth disinfection.
    The hemostatic effect of O> release offers a clear operating field during subgingival debridement. Patients in the test group showed great complacency due to the positive effects of the gel, as mentioned above. Last but not least, during photodynamic therapy, a strong bactericidal effect is created. Through photoactivation of the gel that is in contact with the targeted tissues, a photochemical reaction is created, which accelerates the reactivity of the gel in the synergistic interaction of the three light-tissue-gel components. This interaction consequently increases the generation of the reactive oxygen species (hydrogen peroxide, superoxide ion, singlet oxygen) and at the end of the chain, formation of molecular oxygen (bubbles). In addition, changes in urea compound and water formation are observed. Photosensitizers not only induce energy in the system via electron flow (which increases reactivity to peroxide), but also direct light energy to the biopellicle, since they bind to the biopelicle by itself and to hemoglobin. The impact of the release of free radicals and the corresponding radical cascades on the biological substrate and bacteriologic behavior are not known. These mild biostimulants are lethal to bacterial growth and the complexity of mature biopellets.
    The biostimulation of living multicellular tissues; the bioactive selectivity of cointeraction (light-tissues-gel), light by itself (bactericidal and hyperemic effect) and, last but not least, the micromechanical effect of molecular oxygen, especially in the closed periodontal pocket, should be emphasized and still investigated. This application of the gel is very useful in facilitating the supra and subgingival debridement, in addition to the bactericidal effect, due to photodynamic therapy.
    Although preferred embodiments of the invention have been described above and illustrated in the accompanying drawings, it will be apparent to those skilled in the art that modifications can be made in the same way without deviating from the essence of this invention. Such modifications are considered as possible variants within the scope of the invention.
    权利要求:
    Claims (19)
    [1]
    1. Use of a photoactivated composition for oral disinfection and / or the treatment of an oral disease, where the composition is CHARACTERIZED because it comprises: at least one oxidizer, and at least one photoactivator capable of activating the oxidizer; in combination with a pharmaceutically acceptable carrier.
    [2]
    : 2. Use of the photoactivated composition, according to claim 1, CHARACTERIZED by the fact that the composition still comprises at least one curative factor chosen from hyaluronic acid, glucosamine and allantoin.
    [3]
    3. Use of the photoactivated composition according to either of Claims 1 or 2, CHARACTERIZED by the fact that the oxidant chosen for the composition is chosen from hydrogen peroxide, carbamide peroxide, benzoyl peroxide, an acid peroxide and a percarbonate of alkali metal.
    [4]
    4. Use of the photoactivated composition, according to claim 1, CHARACTERIZED by the fact that the composition still comprises at least one hydrophilic gelling agent.
    [5]
    5. Use of the photoactivated composition according to claim 4, CHARACTERIZED by the fact that the hydrophilic gelling agent chosen for the composition is chosen from glucose, modified starch, methyl cellulose, carboxymethyl cellulose, - propyl cellulose, hydroxypropyl cellulose, polymers carbopol *, alginic acid, sodium alginate, potassium alginate, ammonium alginate, calcium alginate, agar, carrageenan, alfalfa gum, pectin and gelatin.
    [6]
    6. Use of the photoactivated composition, according to claim 1, CHARACTERIZED by the fact that the photoactivator chosen for the composition is chosen from a dye derived from xanthene, an azo dye, a biological ink and a carotenoid.
    [7]
    7. Use of the photoactivated composition, according to claim 6, CHARACTERIZED by the fact that the dye derived from xanthene is chosen from a fluorene dye, a fluorone dye and a rhodol dye.
    [8]
    8. Use of the photoactivated composition according to claim 7, CHARACTERIZED by the fact that the fluorene dye is chosen from a pyronin dye and a rhodamine dye.
    [9]
    9. Use of the photoactivated composition according to claim 8, CHARACTERIZED by the fact that the pyronin dye is chosen from pyronin Y and pyroninB.
    [10]
    10. Use of the photoactivated composition, according to claim 8,
    rhodamine G and rhodamine WT.
    [11]
    11. Use of the photoactivated composition, y, according to claim 7, | CHARACTERIZED by the fact that the fluorone dye is chosen from fluorescein and fluorescein derivatives.
    [12]
    12. Use of the photoactivated composition, according to claim 11, CHARACTERIZED by the fact that the fluorescein derivative is chosen from phloxin B,. cane rose, merbromine, eosin Y, eosin B and erythrosine B.
    [13]
    13. Use of the photoactivated composition, according to claim 6, 'CHARACTERIZED by the fact that the azo dye is chosen from methyl violet, neutral red, para-red, amaranth, carmosine, allura AC red, tartrazine, orange G, ponceau 4R, methyl red and ammonium murexide-purpurate.
    [14]
    14. Use of the photoactivated composition, according to claim 6, CHARACTERIZED by the fact that the biological ink is chosen from safranin O, basic fuchsin, acid fuscine, 3.3 'dihexylocarbocyanine iodide, carminic acid and green indocyanine.
    [15]
    15. Use of the photoactivated composition, according to claim 6, CHARACTERIZED by the fact that the carotenoid is chosen from crocetin, a-crocine (S, S-diapox-S, S-carotenoic acid), zeaxanthin, lycopene, a- carotene, B-carotene, bixin and fucoxanthin.
    [16]
    16. Use of the photoactivated composition, according to claim 6, CHARACTERIZED by the fact that the carotenoid is present in the composition as a mixture chosen from reddish powder obtained from saffron, annatto extract and brown algae extract.
    [17]
    17. Use of the photoactivated composition, according to any one of claims 1 to 16, CHARACTERIZED by the fact that the composition also comprises at least one chelating agent chosen from ethylene diaminetetraacetic acid (EDTA) and ethylene glycoletraetraacetic acid (EGTA) .
    [18]
    18. Use of the photoactivated composition as defined in any one of claims 1 to 17, CHARACTERIZED for being in the manufacture of a medicine for - oral disinfection and / or the treatment of an oral disease.
    [19]
    19. Use, according to claim 1 or 18, CHARACTERIZED by the fact that the oral disease is gingivitis, periodontitis, periodontal disease, oral thrush, lichen planus, stomatitis, herpes simplex injury, oral mucositis, oral ulcers, submucosal fibrosis oral and glossitis.
    i
    AA sf cia - fº ad | 2 in | »And bt. : rs - s P e. ” 'V: f h U | 5 B 7 A; Si r
    TES
    LP “s"): * Fo eo a Sei Dc º |
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    法律状态:
    2020-11-10| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |
    2020-11-10| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2021-05-04| B07E| Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette]|
    2021-05-18| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2021-08-31| B07A| Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]|
    2021-12-07| B350| Update of information on the portal [chapter 15.35 patent gazette]|
    2022-01-11| B09B| Patent application refused [chapter 9.2 patent gazette]|
    优先权:
    申请号 | 申请日 | 专利标题
    US22635409P| true| 2009-07-17|2009-07-17|
    US61/226.354|2009-07-17|
    PCT/CA2010/001134|WO2011006263A1|2009-07-17|2010-07-19|Antibacterial oral composition|
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