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WO2021070896A1 - Agent d'atténuation de l'halitose ou de prévention de l'halitose - Google Patents

Agent d'atténuation de l'halitose ou de prévention de l'halitose Download PDF

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Publication number
WO2021070896A1
WO2021070896A1 PCT/JP2020/038103 JP2020038103W WO2021070896A1 WO 2021070896 A1 WO2021070896 A1 WO 2021070896A1 JP 2020038103 W JP2020038103 W JP 2020038103W WO 2021070896 A1 WO2021070896 A1 WO 2021070896A1
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Prior art keywords
halitosis
group
light
ala
oral cavity
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Ceased
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PCT/JP2020/038103
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English (en)
Japanese (ja)
Inventor
敏則 沖永
隆之 南部
田中　徹
琢也 石井
多田　大
章平 説田
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SBI Pharmaceuticals Co Ltd
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SBI Pharmaceuticals Co Ltd
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Priority to JP2021551697A priority Critical patent/JP7297912B2/ja
Publication of WO2021070896A1 publication Critical patent/WO2021070896A1/fr
Anticipated expiration legal-status Critical
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the present invention contains 5-aminolevulinic acid (hereinafter sometimes referred to as "ALA”) or a derivative thereof or a salt thereof, and irradiates light having a wavelength of 360 nm to 700 nm ALA-photodynamic therapy (hereinafter referred to as "ALA").
  • ALA 5-aminolevulinic acid
  • -PDT ALA-photodynamic therapy
  • PDT photodynamic therapy
  • ALA one of the drugs used for PDT, is known as an intermediate in the pigment biosynthesis pathway widely present in animals, plants and fungi, and is usually biosynthesized from succinyl-CoA and glycine by ALA synthesizer. ..
  • ALA itself is not photosensitive, it is metabolically activated into protoporphyrin IX (hereinafter also referred to as "PpIX") by a series of enzymes in the heme biosynthetic pathway in cells, and is directly directed to tumor tissue and new blood vessels.
  • PpIX protoporphyrin IX
  • An object of the present invention is to provide a preparation that is less invasive to the body and can selectively sterilize halitosis-causing bacteria.
  • the bacteria causing halitosis can be selectively sterilized by administering ALA into the oral cavity and irradiating it with purple light in particular.
  • the invention was completed.
  • R 1 represents a hydrogen atom, an acyl group or an alkoxycarbonyl group
  • R 2 represents a hydrogen atom, an alkyl group, a cycloalkyl group, a cycloalkenyl group, an aryl group or an aralkyl group
  • ALAs pharmaceutically acceptable salts thereof
  • 5-Aminolevulinic acid-a mouth odor improving agent or a mouth odor preventive agent for photodynamic therapy which is administered with a salt thereof and then irradiated with light having a wavelength of 360 nm to 700 nm into the oral cavity.
  • halitosis improving agent or halitosis preventive agent according to [1] or [2], wherein the light having a diameter of 360 nm to 700 nm is light from a light emitting diode or a laser.
  • a method for improving or preventing halitosis in which a compound represented by the above formula (I) or a pharmaceutically acceptable salt thereof is administered into the oral cavity, and then light having a wavelength of 360 nm to 700 nm is irradiated into the oral cavity. ..
  • the conventional method has no choice but to non-selectively kill bacteria in the oral cavity, including halitosis-causing bacteria, and as a result, there is no change in the ratio of the oral flora (the ratio of halitosis-causing bacteria to other bacteria), rather. It is considered that the balance of the oral bacterial flora is impaired and it does not contribute to the improvement of bad breath.
  • the bactericidal action of ALA-PDT using the halitosis improving agent or the halitosis preventive agent of the present invention makes it possible to preferentially sterilize the halitosis-causing bacteria, and the balance of the oral bacterial flora tends to be less. It can shift and provide a radical solution to bad breath.
  • halitosis-causing bacteria that are resident in the human oral cavity induce strong halitosis by changing the proportion in the oral bacterial flora.
  • bad breath is also felt by others rather than by the person himself.
  • halitosis-causing bacteria means that only halitosis-causing bacteria are sterilized and bacteria other than halitosis-causing bacteria are not sterilized, and halitosis-causing bacteria are compared with bacteria other than halitosis-causing bacteria. Includes the meaning of preferentially sterilizing.
  • Streptococcus (Genus) and Streptococcus mitis by analyzing the OTU level at each irradiation intensity when a purple LED is irradiated to a solution obtained by adding ALA to a diluted solution of plaque collected from a subject at a predetermined concentration is shown.
  • the halitosis improver or halitosis preventive agent of the present invention is not particularly limited as long as it contains ALAs and is a halitosis improver or halitosis preventive agent for ALA-PDT that irradiates light having a wavelength of 360 nm to 700 nm.
  • 5-Aminolevulinic acid-photodynamic diagnosis (ALA-PDD) that detects PpIX accumulation sites by irradiating excitation light with a wavelength of 360 nm to 420 nm before ALA-PDT irradiating light with a wavelength of 360 nm to 700 nm. Can also be done.
  • system to which the halitosis improving agent or the halitosis preventive agent of the present invention is applied may be any system provided with an ALA-PDT device, and may be provided with an ALA-class administration device or an ALA-PDD. ..
  • R 1 represents a hydrogen atom, an acyl group or an alkoxycarbonyl group
  • R 2 represents a hydrogen atom, an alkyl group, a cycloalkyl group, a cycloalkenyl group, an aryl group or an aralkyl group. Represent.
  • the acyl group in R 1, a formyl group, an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a valeryl group, an isovaleryl group, a pivaloyl group, a hexanoyl group, an octanoyl group, a linear or branched carbon atoms such as a benzyl group
  • Examples thereof include an alkanoyl group having a number of 1 to 8 and an aloyl group having 7 to 14 carbon atoms such as a benzoyl group, a 1-naphthoyl group and a 2-naphthoyl group.
  • alkoxycarbonyl group in R 1 examples include a linear or branched alkoxycarbonyl group having 1 to 8 carbon atoms such as a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, and an isopropoxycarbonyl group.
  • the alkyl group in R 2 may be straight chain or branched, such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec- butyl group, tert- butyl Examples thereof include a linear or branched alkyl group having 1 to 8 carbon atoms such as a group, a pentyl group, an isopentyl group, a neopentyl group, a hexyl group, a heptyl group, and an octyl group.
  • Examples of the cycloalkyl group in R 2 include a cycloalkyl group having 3 to 8 carbon atoms such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group and a cyclododecyl group.
  • the cycloalkenyl group in R 2 mention may be made of 1-cyclopentenyl group, 1-cycloalkenyl group having 3 to 8 carbon atoms, cyclohexenyl group.
  • Examples of the aryl group in R 2 include an aryl group having 6 to 14 carbon atoms such as a phenyl group, a naphthyl group, an anthryl group and a phenanthryl group.
  • the aralkyl group in R 2 can be the same example as above aryl group
  • the alkyl moiety can be the same example as above alkyl group, specifically, a benzyl group, phenethyl group, phenylpropyl group, phenylbutyl group , Benzyl group, trityl group, naphthylmethyl group, naphthylethyl group and other aralkyl groups having 7 to 20 carbon atoms can be mentioned.
  • R 1 and R 2 may have a substituent within a chemically acceptable range, if necessary, and examples of such a substituent include a halogen atom, an alkyl group, a haloalkyl group, and an alkoxy group. , Nitro group, aryl group and the like.
  • any derivative of ALA capable of forming PpIX in vivo is preferable, and for example, ALA is formed as an ALA prodrug or an intermediate capable of forming ALA in vivo.
  • Examples include ALA prodrugs that are converted (eg, enzymatically) to porphyrins without the need for porphyrins, with ALA esters being preferred.
  • ALA ester examples include ALA methyl ester, ALA ethyl ester, ALA n-propyl ester, ALA n-butyl ester, ALA n-pentyl ester, ALA n-hexyl ester, ALA n-octyl ester, and ALA 2-methoxyethyl.
  • the compound represented by the formula (I) can be administered as various salts for increasing solubility depending on the form of administration.
  • the salt of the compound represented by the formula (I) include a pharmacologically acceptable acid addition salt, metal salt, ammonium salt, organic amine addition salt and the like.
  • each inorganic acid salt such as hydrochloride, hydrobromide, hydroiodide, phosphate, nitrate, sulfate, formate, acetate, propionate, toluenesulfonic acid Salt, succinate, oxalate, lactate, tartrate, glycolate, methanesulfonate, butyrate, valerate, citrate, fumarate, maleate, malate, etc.
  • the metal salt include alkali metal salts such as lithium salt, sodium salt and potassium salt, alkaline earth metal salts such as magnesium and calcium salt, and metal salts such as aluminum and zinc.
  • ammonium salt examples include alkylammonium salts such as ammonium salt and tetramethylammonium salt.
  • organic amine salt examples include each salt such as triethylamine salt, piperidine salt, morpholine salt, and toluidine salt. These salts can also be used as a solution at the time of use.
  • ALAs examples include ALA; various esters such as ALA methyl ester, ALA ethyl ester, ALA propyl ester, ALA butyl ester, and ALA pentyl ester; and these hydrochlorides, phosphates, and sulfates.
  • ALA hydrochloride and ALA phosphate are particularly preferred.
  • the above ALAs can be produced by any known method of chemical synthesis, production by microorganisms, and production by enzymes.
  • the above ALAs may form a hydrate or a solvate, and either one may be used alone or two or more thereof may be used in combination as appropriate.
  • Hematoporphyrin derivative HpD
  • Hematoporphyrin such as Photofrin (registered trademark) (Quadra Logic Technologies, Vancouver, Canada), Hematoporphyrin IX (HpIX); Photosan III (Seahof Laboratorium, Inc., Siehoff, Wesselbrenerkov, Germany); Tetra (m-hydroxyphenyl) chlorin (m-THPC), Bacteriochlorin (Scotia Pharmaceutical Company, Sally, UK), Mono-L-Asparatyl Chlorin e6 (NPe6) (Japan) Petrochemical Company, California, USA), Chlorin e6 (Porphyrin Products), Benzoporphyrin (Quadra Logic Technologies, Vancouver, Canada) (eg, benzoporphyrin derivative monoacid ring A, BPD-MA), Purpurine (PDT)
  • IX hematoporphyrin diester
  • uroporphyrin coproporphyrin
  • juuteroporphyrin polyhematoporphyrin
  • PGP polyhematoporphyrin
  • tetracycline eg, Topicycline®
  • Shire Shire
  • the ALAs can be administered with compounds having other activities that can enhance the photosensitizing effect and thus promote PDT.
  • compounds having other activities include chelating agents, and more specifically, in the literature on aminopolycarboxylic acid, metal detoxification, or the literature on chelation of paramagnetic metal ions in contrasting agents used in magnetic resonance imaging. Examples thereof include the listed chelating agents, and more specifically, ethylenediamine-N, N, N', N'-tetraacetic acid (EDTA), 1,2-diaminocyclohexane-N, N, N', N.
  • EDTA ethylenediamine-N, N, N', N'-tetraacetic acid
  • CDTA diethylenetriamine-N, N, N', N'', N'-pentetic acid
  • DTPA 1,4,7,10-tetraazacyclododecane-1,4,7
  • Examples thereof include 10-tetraacetic acid (DOTA), desferrioxamine or well-known derivatives / analogs thereof, which can be used alone or in admixture of two or more.
  • the chelating agent is typically used at a concentration of 0.05 to 20% (w / v), for example at a concentration of 0.1 to 10% (w / v).
  • administration of ALAs to the oral cavity means administration to a place in the oral cavity where halitosis-causing bacteria are considered to be present, and spraying or application is particularly preferable.
  • the method for administering the halitosis improving agent or the halitosis preventive agent of the present invention is not particularly limited, and examples thereof include spraying with a spray and application with a roller.
  • Examples of the dosage form of the halitosis improving agent or halitosis preventive agent of the present invention include gels, creams, ointments, sprays, lotions, aerosols, and external liquids.
  • the concentration of ALA contained varies depending on various factors including the chemical properties, chemical composition, administration method and degree of halitosis to be improved or prevented.
  • a concentration range of less than 50% (w / v) is preferable, 0.05 to 16% (w / v) is more preferable, 0.5 to 14% (w / v) is particularly preferable, and for example, 1 A range of 5 to 12.0% (w / v) or 2 to 10% (w / v) can be preferably exemplified.
  • ALAs are administered into the oral cavity, and PpIX induced via the heme biosynthesis pathway is intracellular in the halitosis-causing bacteria.
  • the bacteria that are considered to be the causative bacteria of halitosis specifically, the bacteria belonging to the phylum Bacteroidetes, the phylum Fusobacterium Bacteria to which it belongs, such as the genus Solobacterium, can be sterilized, but without affecting bacteria other than the halitosis-causing bacteria that make up a healthy oral flora, such as Streptococcus mitis, or By reducing the amount, it is possible to preferentially kill the bacteria that cause halitosis.
  • the halitosis improving agent or the halitosis preventive agent of the present invention is administered into the oral cavity, and a specific time has passed before the site to be improved or prevented is exposed in order to obtain a desired photosensitizing effect. Is preferable. It is preferable that the excess halitosis improving agent or halitosis preventive agent is removed before the exposure.
  • the time from administration to exposure depends on the type of ALA, conditions to be improved or prevented, and the form of administration.
  • the time is, for example, about 3 to 6 hours, preferably 0 to 90 minutes, 5 to 90 minutes, 30 to 90 minutes, and particularly preferably 10 to 50 minutes.
  • photoactivation can be performed using a light source known in the art, for example, a light emitting diode such as a purple LED, a blue LED, or a red LED, or a purple semiconductor.
  • a light emitting diode such as a purple LED, a blue LED, or a red LED, or a purple semiconductor.
  • Examples include lasers, lasers such as semiconductor lasers such as red semiconductor lasers, and discharge lamps having a strong purple, blue or red light emitting spectrum, but the point is that the device becomes compact and is advantageous in terms of cost and portability.
  • LEDs light emitting diodes
  • LEDs such as purple LEDs, blue LEDs, and red LEDs, or lasers can be preferably exemplified.
  • the wavelength of the light used for irradiation can be selected in order to obtain a more efficient photosensitizing effect, and examples thereof include light in the range of 360 to 700 nm, particularly light having a purple wavelength close to ultraviolet light. Therefore, light having a wavelength in the range of at least 360 nm to 420 nm is preferable, and more specifically, light having a wavelength in the range of 360 to 420 nm, 380 to 420 nm, 403 to 410 nm, etc. can be mentioned, and 408 nm is particularly preferable. ..
  • the energy density is preferably in the range of 10 ⁇ 200J / cm 2, more preferably in the range of 10 ⁇ 100J / cm 2, particularly preferably in the range of 20 ⁇ 60J / cm 2.
  • the power density of the light source used is not particularly limited as long as the effect of the present invention is exhibited, and is preferably in the range of 15 to 400 mW / cm 2 , preferably 15 to 50 mW / cm 2 , 5 to 40 mW / cm.
  • the range of 2 , 10 to 35 mW / cm 2 is more preferable, and the range of 15 to 35 mW / cm 2 is particularly preferable.
  • the irradiation light may be continuous light or pulsed light, but pulsed light is more preferable in that damage to a normal skin surface can be reduced by using pulsed light.
  • the light irradiation time depends on the energy density and the power density, but it is desirable to carry out the light irradiation time for 5 to 30 minutes, preferably 15 minutes.
  • the irradiation may be performed only once, or for example, the irradiation interval may be 1 to 10 minutes, and the light irradiation amount may be divided into several parts and used as light irradiation.
  • a small-diameter optical fiber for a light source can be mentioned, and as a light source of the excitation light to be irradiated in the ALA-PDT step for exciting the accumulated PpIX, PpIX is also used for the breeding site of a minute odor-causing bacterium.
  • a semiconductor laser or LED light source having a strong radiation illuminance to enable the excitation of the light and a narrow irradiation area to enable accurate automatic identification is preferable, and the excitation light is guided and emitted from one end to the outside. It is preferable to have an excitation light light source unit, and specific examples of the excitation light light source unit include a small-diameter optical fiber.
  • a semiconductor mixed crystal such as InGaN can be used, and purple light can be oscillated by changing the blending ratio of InGaN.
  • a compact laser diode having a diameter of about 5.6 mm can be preferably exemplified.
  • a device in which the port for 4 laser outputs from the laser diode and the port for spectrum measurement are about the size of a desktop PC connected by a built-in high-sensitivity spectrometer can be illustrated.
  • a pen-type LED light, a stick-type LED light, a flashlight-type LED light, a toothbrush equipped with / equipped with an LED light, or the like can also be used.
  • ALA-PDD can also be performed in the improvement method or the prevention method using the improver or preventive agent of the present invention.
  • ALA-PDD identifies the attachment site of halitosis-causing bacteria by irradiating PpIX accumulated in the cells of halitosis-causing bacteria with purple light before ALA-PDT of the present invention to emit red fluorescence. It is a judgment method to be performed.
  • the ALA-PDD device used in the ALA-PDD step include an excitation light irradiation device of PpIX, a red fluorescence detection device peculiar to PpIX in an excited state, or a device in which these are integrated.
  • the light emitted from the PpIX excitation light irradiation device As the light emitted from the PpIX excitation light irradiation device, light having a wavelength at which red fluorescence peculiar to PpIX can be observed by exciting PpIX is preferable, and purple close to ultraviolet light belonging to the absorption peak of PpIX belonging to the so-called Soret band.
  • the light having a wavelength of at least 360 nm to 420 nm may be used, and examples thereof include 360 to 420 nm and 403 to 410 nm, with 408 nm being preferable.
  • a known light source can be used, and examples thereof include a purple LED, preferably a flashlight type purple LED, and a light source such as a semiconductor laser.
  • a purple LED which makes the device compact and is advantageous in terms of cost and portability, particularly a flashlight type purple LED and a purple semiconductor diode can be preferably exemplified.
  • the fluorescence having a wavelength of 610 nm to 750 nm, preferably 625 to 638 nm, for determining the propagation range of the halitosis-causing protozoa to be irradiated.
  • the red fluorescence detection device include a detection device with the naked eye and a detection device with a CCD camera.
  • Examples of the ALA-PDD device in which the excitation light irradiation device and the red fluorescence detection device are integrated include a light source and a small-diameter optical fiber for measurement, and the excitation to be irradiated in the ALA-PDD step for exciting the accumulated PpIX.
  • a light source of light a semiconductor laser light source having a strong radiation illuminance to enable detection of PpIX even at a breeding site of a minute odor-causing bacterium and a narrow irradiation area to enable accurate automatic identification.
  • an excitation light light source portion that guides the excitation light and emits it to the outside from one end
  • specific examples of the excitation light light guide unit include a small-diameter optical fiber.
  • a semiconductor mixed crystal such as InGaN can be used, and purple light can be oscillated by changing the blending ratio of InGaN.
  • a compact laser diode having a diameter of about 5.6 mm can be preferably exemplified.
  • a device in which the port for 4 laser outputs from the laser diode and the port for spectrum measurement are about the size of a desktop PC connected by a built-in high-sensitivity spectrometer can be illustrated.
  • a small-diameter optical fiber for measurement is used, and the small-diameter optical fiber for measurement is integrated with the small-diameter optical fiber for a light source, and the received fluorescence is received. Is guided to the detector to determine the PpIX accumulation site.
  • Interdental plaque was collected from 6 healthy adults using dental floss (manufactured by Okina). The subject was asked to refrain from eating and drinking from 1 hour before collection, and confirmed that he had not used antibacterial drugs for 1 month before collection.
  • the collected interdental plaque was transferred from the floss to a sterile plastic tube using 100 ⁇ L of phosphate buffered saline (PBS). It was placed in an anaerobic chamber (environment of 80% nitrogen, 10% hydrogen, 10% carbon dioxide) in an ice-cooled state, and a uniform plaque suspension was prepared by pipetting.
  • PBS phosphate buffered saline
  • ALA 0.15 g was dissolved in 1.2 ml of PBS, and 0.3 ml of 10N NaOH solution was further added to prepare an ALA solution having a pH of 5.0.
  • the plaque bacterial dilution solution and the ALA solution were placed in a 12-well plate to adjust the final concentration of ALA to 0.1% (w / v).
  • the mixture was allowed to stand in a dark place under anaerobic conditions at 37 ° C., and after 2 hours, a purple LED (peak wavelength 400 to 410 nm) was irradiated with an Aladuck LS-DLED (manufactured by SBI Pharma Co., Ltd.) at an irradiation density of 0.18 W / cm 2 .
  • each well was irradiated so that the irradiation energy density was 5, 10, 25, and 50 J / cm 2.
  • 100 ⁇ L of the bacterial solution collected from each well was mixed with 900 ⁇ L SHI medium and cultured with shaking in an anaerobic chamber for 20 hours. After centrifugation the sample, the precipitate was stored at ⁇ 80 ° C. until DNA extraction.
  • Bacterial DNA was extracted from the above-mentioned diluted bacterial plaque solution and the above-mentioned precipitate after culturing using Pathogen Lysis Tube (S) (manufactured by Qiagen) and QIAamp UCP Pathogen Mini Kit (manufactured by Qiagen). After measuring the DNA concentration with Qubit dsDNA BR Assay Kit (manufactured by Thermo Fisher), PCR amplification was performed targeting the bacterial 16S rRNA gene V3-V4 region.
  • S Pathogen Lysis Tube
  • QIAamp UCP Pathogen Mini Kit manufactured by Qiagen
  • the PCR product was purified by AMPure Beads (manufactured by Beckman Coulter), and then the gene sequence was comprehensively decoded by a next-generation sequencer (MiSeq, manufactured by Illumina).
  • the analysis and statistical processing of the obtained sequence data are performed by next-generation sequence analysis software (CLC Genomics Workbench, manufactured by Fischer's) and R script workflow (Rhea) (Lagkouvardos I, Fischer S, Kumar N, Clavel T. Rhea: A transparent and modular R pipeline for microbial profiling based on 16S rRNA gene amplicons. PeerJ. 2017, 11 (5), e2836) was used to determine changes in the bacterial flora.
  • the improvement method by ALA-PDT using the halitosis improving agent of the present invention is, for example, Streptococcus mitis (Ogata K et al .: Effect) known as a bacterium other than the halitosis-causing bacteria constituting a healthy oral flora. of coffee on the compositional shift of oral indigenous microbiota cultured invitro. J Oral Sci. 2019, 61 (3), 418-424; Takeshita T et al .: Bacterial diversity in saliva and oral health-related conditions: the Hisayama Study Sci Rep (See 2016, 6. 22164.), There was no effect on the relative abundance (%) before and after irradiation with the purple LED (Fig. 4), so it affected bacteria other than the bacteria that cause halitosis. It turned out that it may not be given.
  • Streptococcus mitis (Ogata K et al .: Effect) known as a bacterium other than the halitosis-causing bacteria constitu
  • FIG. 1 The ⁇ diversity was shifted in a certain direction by light irradiation (Fig. 1), and according to FIGS. 2 and 3, the balance of the oral flora by ALA-PDT using the halitosis improving agent or halitosis preventive agent of the present invention.
  • FIG. 3 suggests that bacteria that have been pointed out to be associated with halitosis can be sterilized.
  • ALA-PDT using the halitosis improving agent or the halitosis preventive agent of the present invention causes halitosis. It was suggested that this method can sterilize the bacteria that cause halitosis without affecting or reducing the bacteria other than the bacteria that cause halitosis.
  • the halitosis improving agent, halitosis preventive agent, and halitosis improving method and preventing method of the present invention can selectively sterilize halitosis-causing bacteria and are less bioinvasive. Therefore, the medical field and health for improving or preventing halitosis. It can be used in the field of care.

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Abstract

La présente invention aborde le problème de la fourniture d'une préparation pharmaceutique qui envahit peu le corps humain et qui peut tuer sélectivement des bactéries responsables de l'halitose.　Selon la présente invention, un composé représenté par la formule (I) (où R1 représente un atome d'hydrogène ou un groupe acyle ou alcoxycarbonyle et R2 représente un atome d'hydrogène ou un groupe alkyle, cycloalkyle, cycloalcényle, aryle ou aralkyle) ou un sel pharmacologiquement acceptable du composé est administré à l'intérieur de la bouche, qui est ensuite exposé à de la lumière ayant une longueur d'onde comprise entre 360 et 700 nm.
PCT/JP2020/038103 2019-10-09 2020-10-08 Agent d'atténuation de l'halitose ou de prévention de l'halitose Ceased WO2021070896A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006047868A1 (fr) * 2004-11-02 2006-05-11 John Kennedy Methode de traitement photodynamique des micro-organismes dans la cavite buccale mettant en oeuvre une source de lumiere non coherente
WO2013005379A1 (fr) * 2011-07-01 2013-01-10 Ｓｂｉファーマ株式会社 Thérapie photodynamique utilisant un agent photosensibilisateur ou de l'acide 5-aminolévulinique
US20170326383A1 (en) * 2016-05-11 2017-11-16 The Forsyth Institute Animal phototherapeutic system

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090285766A1 (en) * 2005-06-13 2009-11-19 National University Of Singapore Photosensitising Composition and Uses Thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006047868A1 (fr) * 2004-11-02 2006-05-11 John Kennedy Methode de traitement photodynamique des micro-organismes dans la cavite buccale mettant en oeuvre une source de lumiere non coherente
WO2013005379A1 (fr) * 2011-07-01 2013-01-10 Ｓｂｉファーマ株式会社 Thérapie photodynamique utilisant un agent photosensibilisateur ou de l'acide 5-aminolévulinique
US20170326383A1 (en) * 2016-05-11 2017-11-16 The Forsyth Institute Animal phototherapeutic system

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
RAI, M. ET AL.: "Light activated antimicrobial agents can inactivate oral malodour causing bacteria", JOURNAL OF BREATH RESEARCH, vol. 10, no. 4, 18 October 2016 (2016-10-18), pages 046009, XP055817451 *

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