WO2017135048A1 - 光線力学療法用組成物、治療方法、殺菌システムおよび殺菌システムの作動方法 - Google Patents

光線力学療法用組成物、治療方法、殺菌システムおよび殺菌システムの作動方法 Download PDF

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WO2017135048A1
WO2017135048A1 PCT/JP2017/001727 JP2017001727W WO2017135048A1 WO 2017135048 A1 WO2017135048 A1 WO 2017135048A1 JP 2017001727 W JP2017001727 W JP 2017001727W WO 2017135048 A1 WO2017135048 A1 WO 2017135048A1
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composition
control unit
light
calculation
imaging
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PCT/JP2017/001727
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English (en)
French (fr)
Japanese (ja)
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浩二 小笠原
西垣　純爾
能伸 大崎
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富士フイルム株式会社
国立大学法人旭川医科大学
浩二 小笠原
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Priority to CN201780005825.4A priority Critical patent/CN108463249A/zh
Priority to KR1020187019978A priority patent/KR102203314B1/ko
Priority to JP2017565467A priority patent/JP6602400B2/ja
Publication of WO2017135048A1 publication Critical patent/WO2017135048A1/ja

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    • 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
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • 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
    • A61P31/10—Antimycotics
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to a composition for photodynamic therapy, a treatment method, a sterilization system, and a method for operating the sterilization system. More particularly, the present invention relates to a composition for photodynamic therapy for treating H. pylori infection, a method for treating H. pylori infection, a sterilization system for lesions caused by H. pylori infection, and H. pylori infection.
  • Method of operating lesion sterilization system, photodynamic therapy composition for treating mucocutaneous infection, method of treating mucocutaneous infection, sterilization system of lesion due to mucocutaneous infection, and mucocutaneous infection The present invention relates to a method for operating a sterilization system for a lesion caused by a disease.
  • photosensitizers photosensitive substances
  • pathogenic microorganisms present in lesions of infectious diseases such as skin and mucous membranes, and light is emitted by irradiating light of a wavelength corresponding to the photosensitizer. It is a method for treating cutaneous mucosal infection by generating active oxygen from a sensitizer and sterilizing pathogenic microorganisms.
  • Methylene blue has been put to practical use in clinical settings and daily life as a drug for methemoglobinemia, a dye in contrast methods for chromoendoscopy, a stain in dyeing methods, and a fish disease drug. It is.
  • Patent Document 1 discloses the use of methylene blue as an antibacterial agent in the dental field by inducing cell death by singlet oxygen generated by light absorption.
  • methylene blue alone has a weak antibacterial activity and requires a large amount of application with an ointment, which limits its application to oral infections.
  • Non-Patent Document 1 reports that a hydrophobic derivative of methylene blue showed a stronger killing effect than MRA against MRSA (methicillin-resistant Staphylococcus aureus) and VRSA (vancomycin-resistant Staphylococcus aureus). ing.
  • MRSA methicillin-resistant Staphylococcus aureus
  • VRSA vancomycin-resistant Staphylococcus aureus
  • the present invention provides a photodynamic therapy composition for treating H. pylori infection, a photosensitizing effect strong and safe, a method for treating H. pylori infection, and a sterilization system for lesions caused by H. pylori infection And a method for operating a system for sterilizing a lesion caused by Helicobacter pylori infection, and a photodynamic therapy composition for treating skin mucosal infection, which has a strong photosensitizing effect and is safe, and mucosal mucosa It is an object of the present invention to provide a method for treating an infection, a sterilization system for a lesion caused by a mucocutaneous infection, and a method for operating the sterilization system for a lesion caused by a skin mucosal infection.
  • the present invention provides the following [1] to [22].
  • [1] A composition for photodynamic therapy for treating H. pylori infection comprising methylene blue and having a pH of 7.6 to 9.5.
  • composition for photodynamic therapy for treating a H. pylori infection according to any one of [5].
  • composition for photodynamic therapy for treating a Helicobacter pylori infection according to any one of [1] to [6] described above is applied endoscopically to a lesioned part of a Helicobacter pylori infection.
  • a method for treating H. pylori infection which is applied and irradiated with white light or LED light or laser light having a wavelength of 660 ⁇ 10 nm.
  • a composition for photodynamic therapy for treating cutaneous mucosal infection comprising methylene blue and having a pH of 7.6 to 9.5.
  • a composition for photodynamic therapy for treating infectious diseases comprising methylene blue and having a pH of 7.6 to 9.5.
  • the pathogenic microorganism is selected from the group consisting of Candida albicans, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.
  • the composition for photodynamic therapy for treating a mucocutaneous infection according to the above [13] which is at least one.
  • the mucocutaneous infection is at least one selected from the group consisting of candidiasis, methicillin-resistant Staphylococcus aureus infection, Pseudomonas aeruginosa infection, and E. coli infection.
  • the composition for photodynamic therapy for treating skin mucosal infection as described in any one of these.
  • the composition for photodynamic therapy for treating cutaneous mucosal infection according to any one of the above [9] to [15] is applied to a lesion site of the cutaneous mucosal infection, and white light or A method for treating a mucocutaneous infection, which is irradiated with LED light or laser light having a wavelength of 660 ⁇ 10 nm.
  • Imaging means for controlling the imaging direction of the imaging means, irradiation direction control means for controlling the light irradiation direction of the light irradiation means, An injection direction control means for controlling the injection direction of the composition injection means, the imaging means, the light irradiation means, the composition injection means, the imaging direction control means, the irradiation direction control means, and the injection direction control means.
  • a sterilization system for lesions caused by Helicobacter pylori infection comprising a calculation / control unit for controlling, (a) The imaging direction control means and the irradiation direction control means operate based on a control signal from the calculation / control unit so that the light irradiation means illuminates the observation area of the imaging means, (b) The imaging means images the mucous membrane based on the control signal from the calculation / control unit, and transmits a video signal to the calculation / control unit, (c) The calculation / control unit receives the video signal transmitted from the imaging means, performs video processing so as to emphasize the color difference between the normal region and the abnormal region of the mucous membrane, Identify the location of the lesion, (d) The injection direction control means operates based on a control signal from the calculation / control unit so as to match the injection direction of the composition injection means with the lesioned part, (e) The composition injection means comprises a photodynamic for treating the Helicobacter pylori infection according to any one of [1]
  • the irradiation direction control means operates to match the irradiation direction of the light irradiation means with the lesioned part based on a control signal from the calculation / control unit, and (g) The light irradiation means emits white light or LED light or laser light having a wavelength of 660 ⁇ 10 nm based on a control signal from the calculation / control unit. Sterilization system for lesions caused by Helicobacter pylori infection.
  • Imaging means for controlling the imaging direction of the imaging means, irradiation direction control means for controlling the light irradiation direction of the light irradiation means, An injection direction control means for controlling the injection direction of the composition injection means, the imaging means, the light irradiation means, the composition injection means, the imaging direction control means, the irradiation direction control means, and the injection direction control means.
  • An operation method of a sterilization system for a lesion caused by Helicobacter pylori infection comprising a calculation / control unit for controlling, (a) actuating the imaging direction control unit and the irradiation direction control unit based on a control signal from the calculation / control unit so that the light irradiation unit illuminates the observation region of the imaging unit; (b) a step of imaging the mucous membrane based on a control signal from the calculation / control unit, and transmitting a video signal to the calculation / control unit, the imaging means; (c) The calculation / control unit receives the video signal transmitted from the imaging means, performs video processing so as to emphasize the color difference between the normal region and the abnormal region of the mucous membrane, And identifying the location of the lesion, (d) a step of operating the injection direction control unit based on a control signal from the calculation / control unit so as to match the injection direction of the composition injection unit with a lesioned part, (e) Photodynamics for treating the Helico
  • the light irradiation means includes a step of emitting white light or LED light or laser light having a wavelength of 660 ⁇ 10 nm based on a control signal from the calculation / control unit. How to operate the sterilization system.
  • Imaging means for controlling the imaging direction of the imaging means, irradiation direction control means for controlling the light irradiation direction of the light irradiation means, An injection direction control means for controlling the injection direction of the composition injection means, the imaging means, the light irradiation means, the composition injection means, the imaging direction control means, the irradiation direction control means, and the injection direction control means.
  • a sterilization system for lesions caused by mucocutaneous infections comprising a calculation / control unit for controlling, (a) The imaging direction control means and the irradiation direction control means operate based on a control signal from the calculation / control unit so that the light irradiation means illuminates the observation area of the imaging means, (b) The imaging means, based on a control signal from the calculation / control unit, images the skin or mucous membrane, transmits a video signal to the calculation / control unit, (c) The calculation / control unit receives the video signal transmitted from the imaging means, performs video processing so as to emphasize the color difference between the normal region and the abnormal region of the skin or mucous membrane, Identify the lesion, locate the lesion, (d) The injection direction control means operates based on a control signal from the calculation / control unit so as to match the injection direction of the composition injection means with the lesioned part, (e) The composition ejecting means is a photodynamic for treating the mucocutaneous infection according to any one of [9
  • the irradiation direction control means operates to match the irradiation direction of the light irradiation means with the lesioned part based on a control signal from the calculation / control unit, and (g) The light irradiation means emits white light or LED light or laser light having a wavelength of 660 ⁇ 10 nm based on a control signal from the calculation / control unit. Sterilization system for lesions caused by mucocutaneous infections.
  • Imaging means for controlling the imaging direction of the imaging means, irradiation direction control means for controlling the light irradiation direction of the light irradiation means, An injection direction control means for controlling the injection direction of the composition injection means, the imaging means, the light irradiation means, the composition injection means, the imaging direction control means, the irradiation direction control means, and the injection direction control means.
  • An operation method of a sterilization system for a lesion caused by a mucocutaneous infection comprising a calculation / control unit for controlling, (a) actuating the imaging direction control unit and the irradiation direction control unit based on a control signal from the calculation / control unit so that the light irradiation unit illuminates the observation region of the imaging unit; (b) a step of imaging the skin or mucous membrane based on a control signal from the calculation / control unit and transmitting a video signal to the calculation / control unit, (c) The calculation / control unit receives the video signal transmitted from the imaging means, performs video processing so as to emphasize the color difference between the normal region and abnormal region of the skin or mucous membrane, Identifying the lesion and identifying the location of the lesion, (d) a step of operating the injection direction control unit based on a control signal from the calculation / control unit so as to match the injection direction of the composition injection unit with a lesioned part, (e) Photodynamics for treating the mu
  • the light irradiation means includes a step of emitting white light, LED light having a wavelength of 660 ⁇ 10 nm or laser light based on a control signal from the calculation / control unit, and How to operate the sterilization system.
  • a photodynamic therapy composition for treating H. pylori infection, a photosensitizing effect strong and safe a method for treating H. pylori infection, and a sterilization system for lesions caused by H. pylori infection
  • a method for operating a system for sterilizing a lesion caused by Helicobacter pylori infection and a photodynamic therapy composition for treating skin mucosal infection, which has a strong photosensitizing effect and is safe, and mucosal mucosa
  • FIG. 1 is a conceptual diagram showing a sterilization system according to the present invention.
  • FIG. 2 is a perspective view showing a specific example of the sterilization system according to the present invention.
  • FIG. 3A is a front view showing a distal end cap of the endoscope.
  • FIG. 3B is a front view showing another aspect of the distal end cap of the endoscope.
  • FIG. 4A is a cross-sectional view showing a flexible tube portion of an endoscope.
  • FIG. 4B is a cross-sectional view showing another aspect of the flexible tube portion of the endoscope.
  • the characteristic point of the present invention is that it is a composition for photodynamic therapy in a specific pH range containing methylene blue whose safety has already been established. Even when adjusting to a specific pH range, a composition for photodynamic therapy having low toxicity and extremely high safety can be obtained by using a pH adjuster whose safety has already been established.
  • the range when a range is expressed using “ ⁇ ”, the range includes both sides of “ ⁇ ”.
  • the range represented by “A to B” includes “A” and “B”.
  • composition for photodynamic therapy for treating H. pylori infection contains methylene blue and has a pH of 7.6 to 9.5.
  • Helicobacter pylori infection is an infection of the mucous membrane caused by Helicobacter pylori, and particularly refers to an infection of the gastric mucosa caused by Helicobacter pylori.
  • Helicobacter pylori, Helicobacter mustelae, Helicobacter mustelae, Helicobacter mustelae, Helicobacter mustelae and Helicobacter ferris are not particularly limited as long as they are bacteria belonging to the genus Helicobacter having urease working under acidic conditions. It is at least one selected from the group consisting of (Helicobacter felis), more preferably Helicobacter pylori.
  • Methylene blue (3,7-bis (dimethylamino) phenothiazinium chloride) contained in the composition for photodynamic therapy for treating H. pylori infection of the present invention is not particularly limited, and for example, an anhydride It may be a hydrate. Examples of the hydrate include, but are not limited to, dihydrate, trihydrate, and tetrahydrate.
  • methylene blue may be sold as a pharmaceutical or may be sold as a reagent. A reagent having a high purity is preferable, and for example, a reagent specified in JIS K 8897: 2012 is more preferable.
  • Methylene blue is safe for the human body to be used for staining during chromoendoscopy of the gastrointestinal tract, intravenously or orally administered in the treatment of drug-induced methemoglobinemia, treatment of ifosfamide encephalopathy It has been established because it is used by intravenous injection. It is low toxic to animals other than humans, and the safety of methylene blue has been established.
  • the concentration of methylene blue when the composition for photodynamic therapy for treating H. pylori infection of the present invention is brought into contact with H. pylori is not particularly limited, but is preferably 0.0007 to 4.0 w / v%, more preferably Is 0.001 to 3.0 w / v%, more preferably 0.003 to 2.0 w / v%, still more preferably 0.005 to 1.0 w / v%, and still more preferably 0.007 to 0. 80 w / v%.
  • the antibacterial activity against H. pylori is further improved.
  • the lowest digit of the concentration is rounded off by one digit below that. For example, “0.001” includes 0.00095 or more and less than 0.0015, and “4.0” includes 3.95 or more and less than 4.05.
  • the pH of the photodynamic therapy composition for treating H. pylori infection of the present invention is 7.6 to 9.5, preferably 8.3 to 9.2, and more preferably 8.5. Is 9.0.
  • the pH when the composition for photodynamic therapy for treating H. pylori infection of the present invention is brought into contact with H. pylori is within this range, the antibacterial activity against H. pylori is excellent.
  • the pH is rounded off to the second decimal place.
  • “7.6” is 7.55 or more and less than 7.65
  • “9.5” is 9.45 or more and less than 9.55. Respectively.
  • the pH was measured with a pH meter using a glass electrode specified in JIS Z 8802: 2011 “pH measurement method”. 25 PH value at ° C.
  • the method for adjusting the pH of the composition for photodynamic therapy for treating H. pylori infection of the present invention is not particularly limited, and examples thereof include a method of adding a pH adjuster.
  • a pH adjuster those having low toxicity to humans or animals other than humans are preferable.
  • citric acid, gluconic acid, succinic acid, lactic acid, sodium hydrogen carbonate (also referred to as “bicarbonate”) examples thereof include sodium carbonate, potassium carbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium dihydrogen phosphate, and disodium hydrogen phosphate.
  • sodium bicarbonate is particularly preferred.
  • sodium hydrogen carbonate When sodium hydrogen carbonate is used as a pH adjuster, the antibacterial activity is further improved.
  • sodium bicarbonate is used as a pH adjuster and when potassium dihydrogen phosphate (KH 2 PO 4 ) and disodium hydrogen phosphate (Na 2 HPO 4 ) are used, the same pH is obtained. Even so, the use of sodium hydrogen carbonate shows superior antibacterial activity.
  • potassium dihydrogen phosphate (KH 2 PO 4 ) and disodium hydrogen phosphate (Na 2 HPO 4 ) the same pH is obtained. Even so, the use of sodium hydrogen carbonate shows superior antibacterial activity.
  • KH 2 PO 4 potassium dihydrogen phosphate
  • Na 2 HPO 4 disodium hydrogen phosphate
  • the addition amount of the pH adjuster is not particularly limited as long as it is added so that the pH of the composition for photodynamic therapy for treating H. pylori infection of the present invention falls within the above-described pH range.
  • sodium bicarbonate sodium bicarbonate
  • the concentration cannot be generally stated, but is preferably, for example, 0.007 to 0.80 w / v%, more preferably 0.01 to 0.70 w / v%, more preferably 0.05 to 0.65 w / v%, even more preferably 0.10 to 0.60 w / v%, and even more preferably 0.15 to 0.40 w. / V%.
  • the antibacterial activity against H. pylori is further improved.
  • the photodynamic therapy composition for treating H. pylori infection of the present invention may further contain a pharmaceutically acceptable additive.
  • Pharmaceutically acceptable additives include pH adjusters, buffers, wetting agents / solubilizers, antibacterial preservatives, chelating agents, complexing agents, antioxidants, sweeteners, and excipients other than those mentioned above Agents, binders, disintegrants, lubricants, fluidizers / anti-caking agents, and suspending agents / adhesives. These additives can be included in the composition for photodynamic therapy for treating H. pylori infections of the present invention alone or in combination of two or more.
  • composition for photodynamic therapy for treating H. pylori infection of the present invention is preferably brought into contact with H. pylori present in a lesion of H. pylori infection and irradiated with light to H. pylori. Used in photodynamic therapy to treat fungal infections.
  • the composition for photodynamic therapy for treating Helicobacter pylori infection of the present invention can be used for humans as well as animals other than humans.
  • non-human animals include, without limitation, non-human mammals including monkeys, cats, pigs, dogs and the like.
  • animals other than humans include, in addition to mammals, vertebrates other than mammals such as birds, reptiles, amphibians, and fish, but are not limited thereto.
  • animals other than humans include domestic animals such as dogs, cats, cows, horses, pigs, sheep, goats, donkeys and camels, and dogs, cats, foxes, raccoons, monkeys, donkeys, and horses.
  • the dosage form of the photodynamic therapy composition for treating H. pylori infection of the present invention is not particularly limited, but is preferably locally administered, particularly preferably endoscopically in the lesioned part of the gastric mucosa. Administration by nebulization directly through a mirror. Specifically, for example, methylene blue and, if necessary, a pH adjusting agent are dissolved in pure water or physiological saline and filled into a syringe having a tube at the tip, and the tube is inserted into the forceps port of the endoscope. The drug can be sprayed onto the stomach wall by pressing.
  • the method for producing the composition for photodynamic therapy for treating H. pylori infection of the present invention is not particularly limited.
  • methylene blue is dissolved in water to produce a methylene blue solution having a desired concentration. Can do. If the pH of the methylene blue solution is not within the range of 7.6 to 9.5, a pH adjuster is added to adjust the pH within the range of 7.6 to 9.5.
  • methylene blue can be dissolved in water or ethanol to prepare a stock solution having a concentration of about 1.0 to 5.0 w / v%, and this stock solution can be diluted with water to produce a methylene blue solution having a desired concentration. Good. Commercially available products may be used as the methylene blue stock solution.
  • stock solutions examples include methylene blue stock solution (manufactured by Kishida Chemical Co., Ltd .; ethanol solution, concentration 5.0 w / v%). .
  • physiological saline sodium chloride concentration: 0.9 w / v%)
  • sterilized purified water sterilized purified water
  • distilled water or the like can be used.
  • the composition for photodynamic therapy for treating H. pylori infection described above is applied endoscopically to a lesioned part of H. pylori infection and white light is applied.
  • LED light or laser light with a wavelength of 660 ⁇ 10 nm is irradiated.
  • H. pylori is a bacterium that infects the gastric mucosa
  • the photodynamic therapy composition for treating H. pylori infection of the present invention is applied to the lesion of H. pylori infection by performing endoscopically. It can be applied more reliably, and it can be applied as little as possible to the non-lesioned part.
  • Differentiation of lesioned and non-lesioned parts includes a method that utilizes the tendency of redness in the lesioned part. This method has an advantage that the load on the gastric mucosa is extremely small because the lesioned part and the non-lesioned part can be distinguished by image processing.
  • the light to be irradiated is white light, LED light having a wavelength of 660 ⁇ 10 nm, or laser light.
  • the light source is not particularly limited as long as it can emit white light or light having the above wavelength.
  • the light source may be a coherent light source or an incoherent light source.
  • the coherent light source include a laser and a laser diode, and an AlGaInP (aluminum gallium indium phosphide) quantum well laser diode or an aluminum gallium arsenide laser having a wavelength of 660 nm is particularly preferable.
  • Examples of incoherent light sources include LEDs (Light Emitting Diodes), incandescent lamps, fluorescent lamps, and xenon lamps.
  • the white light white light that is usually used for observation can be used.
  • the white light may be white light obtained by combining blue laser light having a wavelength of 445 nm and fluorescence excited and emitted from the phosphor by the blue laser light.
  • the phosphors are a plurality of kinds of phosphors that absorb a part of blue laser light and emit light with excitation from green to yellow (for example, YAG (yttrium, aluminum, garnet) phosphors, BAM (barium / aluminum)). It is preferable to use a material including an oxide (phosphor such as BaMgAl 10 O 17 : Eu 2+ ).
  • the light projection amount is not particularly limited, but is preferably 1 to 200 J / m 2 , more preferably 1 to 100 J / m 2 , and further preferably 5 to 100 J / m 2 , and more It is preferably 3 to 30 J / m 2 , and more preferably 5 to 15 J / m 2 . Within this range, a safer and higher sterilizing effect can be expected.
  • the light irradiation time is not particularly limited and can be appropriately set so as to be the above light projection amount. However, for example, it is preferably 30 to 600 seconds, more preferably 30 to 300 seconds, and still more preferably 60. It is ⁇ 300 seconds, more preferably 80 to 240 seconds.
  • the composition for photodynamic therapy for treating H. pylori infection of the present invention can exhibit sufficient antibacterial activity even at a relatively low light projection amount. For example, even a 1400 lux white light source used for normal observation shows antibacterial activity.
  • the method for treating H. pylori infection of the present invention can be applied not only to humans but also to animals other than humans.
  • non-human animals include, without limitation, non-human mammals including monkeys, cats, pigs, dogs and the like.
  • animals other than humans include, in addition to mammals, vertebrates other than mammals such as birds, reptiles, amphibians, and fish, but are not limited thereto.
  • animals other than humans include domestic animals such as dogs, cats, cows, horses, pigs, sheep, goats, donkeys and camels, and dogs, cats, foxes, raccoons, monkeys, donkeys, and horses.
  • the present invention relates to a sterilization system for lesions caused by Helicobacter pylori infection (hereinafter sometimes simply referred to as “the Helicobacter pylori sterilization system of the present invention”) and a method for operating a sterilization system for lesions caused by Helicobacter pylori infection (hereinafter simply referred to as “pylori sterilization system of the present invention”). "It may be referred to as” the method of operating the H. pylori sterilization system of the present invention ").
  • the Helicobacter pylori sterilization system of the present invention ⁇ Disinfection system for lesions caused by Helicobacter pylori infection>
  • the composition for photodynamic therapy for treating H. pylori infection of the present invention may be referred to as “the composition for photodynamic therapy of the present invention”.
  • the Helicobacter pylori sterilization system of the present invention is composed of a sterilization system 100 shown in FIG.
  • the sterilization system 100 includes a calculation / control unit 101, an imaging unit 102, an imaging direction control unit 103, a light irradiation unit 104, an irradiation direction control unit 105, and a composition injection unit 106.
  • the injection direction control means 107 and the transmission paths 108 to 113 are provided.
  • the image pickup means 102 includes an image pickup optical system 102a including an image pickup device (not shown) for picking up an observation region, a signal processing unit for performing analog / digital conversion processing of a video signal from the image pickup device, and an arithmetic / control unit 101. With an interface.
  • the imaging unit 102 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the imaging unit 102 and the calculation / control unit 101 via the transmission path 108.
  • the image sensor is a color image sensor, which captures a reflected image to be photographed and outputs a video signal.
  • the imaging element is preferably a CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal-Oxide Semiconductor: complementary metal oxide semiconductor) image sensor.
  • the imaging direction control means 103 includes a drive mechanism for changing the imaging direction of the imaging means 102 and an interface with the calculation / control unit 101.
  • the imaging direction control means 103 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the imaging direction control unit 103 and the calculation / control unit 101 via the transmission path 109.
  • the light irradiation unit 104 includes an illumination optical system 104a that emits illumination light and / or excitation light, a light source unit that supplies light to the illumination optical system 104a, and an interface with the calculation / control unit 101.
  • the light irradiation unit 104 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the light irradiation unit 104 and the calculation / control unit 101 via the transmission path 110.
  • the light irradiation means 104 may be an integrated type in which the illumination optical system 104a and the light source unit are built in the same housing, or a separate type in which the illumination optical system 104a and the light source unit are built in separate housings. It may be.
  • the illumination light and / or excitation light emitted by the light irradiation means 104 can be appropriately selected depending on the application.
  • white light, daylight white light, daylight color light, light bulb color light, or the like is usually used as light for illuminating the observation region.
  • white light is preferable because a natural color tone of the observation region can be obtained.
  • light that emphasizes the color difference is used. It is preferable.
  • the excitation light for the composition for photodynamic therapy of the present invention it is preferable to irradiate white light, LED light having a wavelength of 660 ⁇ 10 nm, or laser light because methylene blue can be efficiently excited.
  • the irradiation direction control unit 105 includes a drive mechanism for changing the irradiation direction of the light irradiation unit 104 and an interface with the calculation / control unit 101.
  • the irradiation direction control means 105 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the irradiation direction control unit 105 and the calculation / control unit 101 via the transmission path 111.
  • the composition injection means 106 includes an injection unit 106a having an opening for injecting the photodynamic therapy composition of the present invention, a liquid supply tank (not shown) in which the photodynamic therapy composition of the present invention is stored, The liquid feed pump (not shown) for injecting the composition for photodynamic therapy of the present invention and an interface with the calculation / control unit 101 are provided.
  • the composition injection unit 106 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the composition injection unit 106 and the calculation / control unit 101 via the transmission path 112.
  • the composition injection means 106 may be an integrated type in which the injection unit 106a, the liquid supply tank, and the liquid supply pump are built in the same housing, or only the liquid supply tank may be disposed outside.
  • the liquid feeding tank and the liquid feeding pump may be arranged outside, and the liquid feeding tank and the liquid feeding pump may be separated.
  • the opening of the injection unit 106a may be a simple hole or a nozzle capable of spraying the composition for photodynamic therapy of the present invention in a spray form.
  • the injection direction control unit 107 includes a drive mechanism for changing the injection direction of the injection direction control unit 107 and an interface with the calculation / control unit 101.
  • the injection direction control means 107 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the ejection direction control means 107 and the calculation / control unit 101 via the transmission path 113.
  • the transmission paths 108 to 113 may be wired or wireless. In the case of a wired connection, either a metal cable or an optical cable may be used.
  • the imaging direction control unit 103 When the imaging unit 102, the light irradiation unit 104, and the composition ejecting unit 106 move together, the imaging direction control unit 103, the irradiation direction control unit 105, and the ejection direction control unit 107 are integrated into one direction control unit. It may be.
  • the photodynamic therapy composition for treating H. pylori infection of the present invention may be referred to as “the photodynamic therapy composition of the present invention”. is there.
  • the imaging direction control unit 103 and the irradiation direction control unit 105 are operated based on a control signal from the calculation / control unit 101 so that the light irradiation unit 104 illuminates the observation region of the imaging unit 102.
  • the imaging unit 102 images the skin or mucous membrane 200 based on the control signal from the calculation / control unit 101 and transmits a video signal to the calculation / control unit 101.
  • the calculation / control unit 101 receives the video signal transmitted from the imaging unit 102, performs video processing so as to emphasize the color difference between the normal region and the abnormal region of the mucous membrane, and the normal unit 201 and the lesion
  • the part 202 is identified, and the position of the lesioned part 202 is specified.
  • the injection direction control means 107 is operated based on a control signal from the calculation / control unit 101 so that the injection direction of the composition injection means 106 is matched with the lesioned part 202.
  • the composition ejecting means 106 ejects the composition for photodynamic therapy of the present invention based on the control signal from the calculation / control unit 101.
  • the irradiation direction control unit 105 is operated based on a control signal from the calculation / control unit 101 so that the irradiation direction of the light irradiation unit 104 is aligned with the lesioned part 202.
  • the light irradiation means 104 emits white light, LED light having a wavelength of 660 ⁇ 10 nm or laser light based on a control signal from the calculation / control unit 101.
  • light irradiation to the composition for photodynamic therapy is performed as follows instead of (f) and (g) above.
  • (F1) to (g1) may be used.
  • the imaging direction control unit 103 and the irradiation direction control unit 105 are operated based on a control signal from the calculation / control unit 101 so that the light irradiation unit 104 illuminates the observation region of the imaging unit 102.
  • the imaging unit 102 images the skin or mucous membrane 200 based on the control signal from the calculation / control unit 101 and transmits a video signal to the calculation / control unit 101.
  • the calculation / control unit 101 receives the video signal transmitted from the imaging means 102, identifies the normal region and the abnormal region of the mucous membrane, and identifies the presence or absence of adhesion of the photodynamic therapy composition of the present invention. Image processing is performed so as to be able to be performed, and the position of the region where the lesioned part 202 and the attachment part 203 of the composition for photodynamic therapy overlap is specified. (f4) Irradiation direction control means based on a control signal from the calculation / control unit 101 so that the irradiation direction of the light irradiation means 104 matches the region where the lesioned part 202 and the photodynamic therapy composition attachment part 203 overlap. 105 is activated. (g1) The light irradiation unit 104 emits white light, LED light having a wavelength of 660 ⁇ 10 nm, or laser light based on a control signal from the calculation / control unit 101.
  • the sterilization system 10 shown in FIG. 2 includes an endoscope 11, a calculation / control device 12, a light source device 13, an air / water supply device 14, and a liquid supply device 15.
  • the air / water supply device 14 is built in the light source device 13 and is provided outside the light source device 13 and a known air supply pump 14a that generates a delivery pressure of fluid such as air and cleaning water, and stores cleaning water.
  • the cleaning water tank 14b is constituted.
  • the difference from conventional electron microscope systems is that, generally speaking, the calculation / control device 12 shown in FIG.
  • the liquid processing device 15 can supply the composition for photodynamic therapy of the present invention to the endoscope 11, and the endoscope 11 has a video processing unit that identifies the position of the abnormal part.
  • a point that can be discharged from the WJ outlet 24 (see FIGS. 3A and 3B) provided at the distal end portion 16a toward the lesioned portion of the mucous membrane, and illumination windows 22a and 22b provided at the distal end portion 16a of the endoscope 11 ( 3A and FIG. 3B) that white light or LED light or laser light having a wavelength of 660 ⁇ 10 nm can be irradiated to a mucosal lesion or an area where the composition for photodynamic therapy of the present invention is attached. It is in
  • the endoscope 11 shown in FIG. 2 includes an insertion unit 16 to be inserted into a subject, an operation unit 17 connected to a proximal end (rear end) portion of the insertion unit 16, an arithmetic / control device 12, And a universal cord 18 connected to the light source device 13.
  • the insertion portion 16 shown in FIG. 2 is provided at the distal end thereof, and is connected to a distal end portion 16a in which an imaging element (not shown) for in-subject imaging is incorporated, and a proximal end of the distal end portion 16a.
  • the portion 16a is rotatably supported and includes a bendable bendable portion 16b and a flexible flexible tube portion 16c that is connected to the base end of the bendable portion 16b.
  • a tip cap 20 shown in FIGS. 3A and 3B is attached to the tip of the tip portion 16a shown in FIG.
  • the tip cap 20 is provided with an observation window 21, illumination windows 22a and 22b, and a forceps outlet 23 from which the tip of the forceps protrudes.
  • the tip cap 20 has a composition for photodynamic therapy of the present invention, washing water, a chemical solution, and the like for a portion to be observed in the subject (hereinafter sometimes referred to as “observed portion”).
  • a water jet outlet (hereinafter sometimes referred to as “WJ outlet”) 24 for jetting a liquid and an jet nozzle 25 for jetting air or washing water toward the observation window 21 are provided.
  • the observation window 21 is formed in front of the image sensor and allows photographing light incident on the image sensor to pass therethrough.
  • Two illumination windows 22a and 22b are arranged at symmetrical positions with respect to the observation window 21, and irradiate the observation part in the subject with the illumination light from the light source device 13.
  • the forceps outlet 23 shown in FIGS. 3A and 3B communicates with a forceps inlet 26 provided in the operation unit 17 shown in FIG.
  • Various kinds of treatment tools having an injection needle, a high-frequency knife or the like arranged at the tip are inserted into the forceps inlet 26.
  • an air / water button 30 for feeding cleaning water may be provided.
  • the air / water supply button 30 is operated so as to supply air
  • the air supplied from the air supply pump 14 a is sent to the endoscope 11.
  • the air / water supply button 30 is operated so as to perform water supply, the air supplied from the air supply pump 14a is sent to the wash water tank 14b, and the wash water is supplied from the wash water tank 14b by this air pressure. And sent to the endoscope 11.
  • the operation portion 17 receives a control signal from the arithmetic / control device 12, and drives the bending portion up / down bending mechanism and / or the bending portion left / right bending mechanism built in the endoscope 11. Then, the bending portion 16b is bent up and down / left and right.
  • the air supply pump 14a receives a control signal from the arithmetic / control device 12, and the air supply pump 14a operates to supply air to the endoscope 11.
  • the supplied air is sent to the endoscope 11.
  • the air supply pump 14a receives a control signal from the arithmetic / control device 12, operates so that the air supply pump 14a supplies air to the cleaning water tank 14b, and supplies air from the air supply pump 14a.
  • the air that has been aired is sent to the washing water tank 14 b, and the washing water is sent from the washing water tank 14 b by this air pressure and sent to the endoscope 11.
  • the operation unit 17 may be provided with a mode switch 27 and a zoom operation unit 31 in addition.
  • the mode changeover switch 27 is used for a switching operation between two types of modes, a normal observation mode and a special observation mode.
  • the normal observation mode is a mode in which white light is used for illumination of the observation area.
  • the special observation mode is a mode that uses bluish light to illuminate the area to be observed, and emphasizes changes in the color of the mucous membrane and blood see-through to distinguish between normal and abnormal areas of the mucosa This mode makes it easy to distinguish.
  • the zoom operation unit 31 is used for a zoom operation for driving the zooming mechanism in the endoscope 11 to enlarge or reduce the observation image. In the normal observation mode, daylight white light, daylight color light, light bulb color light, or the like may be used instead of white light, and in the special observation mode, white light may be used instead of the special light.
  • a connector 32 is attached to one end of the universal cord 18 shown in FIG.
  • the connector 32 is a composite type connector and is connected to the calculation / control device 12, the light source device 13, and the liquid feeding device 15, respectively.
  • the arithmetic / control apparatus 12 shown in FIG. 2 performs various video processes on the video signal input from the image sensor via the universal code 18 and the connector 32, and generates an endoscopic image.
  • the endoscopic image generated by the arithmetic / control device 12 is displayed on a monitor 33 connected to the arithmetic / control device 12 by a cable.
  • the arithmetic / control device 12 is connected to the light source device 13 via a communication cable, and communicates various control information with the light source device 13.
  • the liquid delivery device 15 shown in FIG. 2 includes a composition for photodynamic therapy according to the present invention, washing water or washing liquid for washing the inside of a subject, or a liquid feeding tank 35 in which a chemical solution is stored, a motor and a control circuit. And a liquid feed pump 37 that is disposed on the front surface of the liquid feed body 36 and that feeds the cleaning liquid stored in the liquid feed tank 35.
  • the liquid feeding device 15 includes a liquid feeding pipe 39 that connects the liquid feeding pump 37 and the connector 32, and a connecting pipe 40 that connects the liquid feeding tank 35 and the liquid feeding pump.
  • the liquid feeding device 15 may include a foot switch 38 for operating the liquid feeding pump 37 to perform a liquid feeding operation. Instead of the foot switch 38, a manually operable switch or a remote controller may be used.
  • the liquid delivery device 15 normally operates based on a control signal from the arithmetic / control device 12.
  • the light guides 41 a and 41 b have one end fixed to the tip cap 20 and the other end connected to the light source device 13 via the universal cord 18 and the connector 32.
  • An illumination optical system (not shown) including an illumination lens (not shown) is incorporated behind the illumination windows 22a and 22b.
  • the light guides 41a and 41b have their emission ends facing illumination lenses disposed behind the illumination windows 22a and 22b, and guide the light from the light source device 13 to the illumination windows 22a and 22b.
  • One end of the forceps tube 42 is fixed to the tip cap 20 and connected to the forceps outlet 23, and the other end is connected to the forceps inlet 26 through the inside of the bending portion 16 b, the flexible tube portion 16 c, the operation portion 17, and the like.
  • the forceps outlet 23 and the forceps inlet 26 communicate with each other.
  • One end of the air / water supply tube 43 is connected to the injection nozzle 25, and the other end is connected to the air / water supply device 14 via the universal cord 18 and the connector 32.
  • the air / water supply tube 43 sends the air and the wash water supplied from the air / water supply device 14 to the injection nozzle 25.
  • the injection nozzle 25 injects air and cleaning water supplied from the air / water supply device 14 toward the observation window 21 to wipe away dirt adhering to the observation window 21.
  • the multi-core cable 44 electrically connects the arithmetic / control device 12 and the image sensor.
  • the multi-core cable 44 includes a plurality of signal cables 44a, and the plurality of signal cables 44a are covered with an outer cover 44b that functions as an electric shield layer.
  • the flexible tube portion 16c includes a screw tube 51 called a flex that protects the inside while maintaining flexibility in order from the inside, and a net 52 called a blade that covers the screw tube 51 and prevents the screw tube 51 from extending. And a flexible rubber 53 covered on the net 52.
  • the outer layer of the curved portion 16 b is also composed of rubber 53.
  • the WJ tube 45 includes a soft rubber WJ soft tube (not shown) that passes through the curved portion 16b and the flexible tube portion 16c, and a hard metal WJ that passes through the tip portion 16a. It consists of a hard tube (not shown), and the photodynamic therapy composition, cleaning solution or chemical solution of the present invention fed by the solution feeding device 15 is sent to the WJ outlet 24.
  • One end of the WJ soft tube passes through the operation unit 17 and is connected to the liquid feeding device 15 via the universal cord 18, the connector 32, and the liquid feeding pipe 39. The other end of the WJ soft tube is connected to the WJ hard tube.
  • the WJ hard tube (not shown) extends in the photographic optical axis direction, and its distal end is bent in a direction substantially perpendicular to the photographic optical axis direction, and an image sensor (not shown) is formed in the radial direction of the distal end portion 16a.
  • a first WJ path (not shown) extending in the photographic optical axis direction at a position away from the optical axis), one end communicating with the WJ outlet 24, and the other end extending in a direction substantially perpendicular to the photographic optical axis direction.
  • a second WJ path 47b in communication.
  • the first WJ path is connected to a WJ soft tube (not shown).
  • the second WJ path is linearly formed on the orthogonal plane orthogonal to the photographing optical axis.
  • the second WJ path may be bent or curved. Also good.
  • the tip end portion 16a is made of a metal cylindrical tip portion main body (not shown) and a metal tip pipe (not shown) covering the tip portion main body.
  • the WJ hard tube (not shown) is fixed to the tip body with the tip inserted into the tip body.
  • the light guides 41a and 41b, the forceps tube 42, and the air / water supply tube 43 are also fixed to the distal end portion main body in a state where the distal end portions are inserted into the distal end portion main body.
  • the distal end pipe has an outer peripheral surface covered with rubber 53, and a distal end cap 20 is attached to the distal end.
  • an imaging optical system including an imaging lens (not shown) and an imaging element (not shown) is arranged.
  • the imaging optical system is fixed to a tip body (not shown).
  • the imaging device is preferably a CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal-Oxide Semiconductor) image sensor.
  • the imaging optical system makes the image light of the observation part incident from the observation window 21 enter the imaging lens, and the imaging lens forms an image on the imaging surface of the imaging element.
  • the calculation / control device 12 and the light source device 13 are turned on, and the insertion portion 16 of the endoscope 11 is inserted into the subject.
  • the light from the light source device 13 is irradiated to the observation part in the subject through the light guides 41a and 41b, the illumination optical system (not shown), and the illumination windows 22a and 22b.
  • the light may be white light, but bluish light may be used in order to emphasize the color difference between the normal area and the abnormal area (lesioned area) of the mucous membrane.
  • An imaging element (not shown) built in the distal end portion 16a of the insertion portion 16 images the inside of the subject and outputs a video signal.
  • This video signal is input to the arithmetic / control device 12 via the universal cord 18 and the connector 32.
  • the arithmetic / control device 12 performs image processing that emphasizes the color difference between the normal area and abnormal area (lesion) of the mucous membrane, and identifies the position of the abnormal area (lesion area) of the mucosa based on the color difference. To do. Further, the arithmetic / control device 12 can perform various video processes on the input video signal to generate an image in the subject, and display the image in the subject on the monitor 33.
  • the calculation / control device 12 When observing the inside of the subject, the calculation / control device 12 outputs a control signal to the operation unit 17 so as to bend the bending portion 16b in the vertical direction and the horizontal direction.
  • This control signal is input to the operation unit 17 via the universal cord 18 and the connector 32, and the operation unit 17 operates the bending portion up-and-down bending mechanism and the bending portion right and left bending mechanism built in the endoscope 11, so that the distal end The direction of the part 16a is changed, and different places of the mucous membrane in the subject are observed.
  • the calculation / control device 12 gives an instruction to the operator, and the operation unit 17 is bent up and down.
  • the angle knob 28 for bending and / or the angle knob 29 for bending left and right may be operated to bend the bending portion 16b in the vertical direction and the horizontal direction.
  • the calculation / control device 12 When the calculation / control device 12 specifies the position of the abnormal region (lesion) in the mucous membrane of the subject, the calculation / control device 12 transmits a control signal to the operation unit 17 to bend the bending portion 16b. The jet direction of the WJ outlet 24 is adjusted to the abnormal region (lesioned portion). Then, a control signal is transmitted to the liquid delivery device 15, the liquid delivery pump 37 is operated, and the composition for photodynamic therapy of the present invention stored in the liquid delivery tank 35 is connected to the connecting tube 40, the liquid delivery pump 37, It is sent to the WJ tube via the liquid feed pipe 39 and the connector 32.
  • composition for photodynamic therapy of the present invention sent to the WJ tube is ejected from the WJ outlet 24 through the WJ soft tube and the WJ hard tube, and includes at least a part of an abnormal region (lesion) of the mucous membrane. Adhere to.
  • the arithmetic / control device 12 transmits a control signal to the light source device 13, and the light from the light source device 13 passes through the light guides 41a and 41b, the illumination optical system (not shown), and the illumination windows 22a and 22b. Then, irradiation is performed toward the region of the mucous membrane of the subject to which the composition for photodynamic therapy of the present invention is attached.
  • the irradiated light is white light, LED light having a wavelength of 660 ⁇ 10 nm, or laser light.
  • the position of the part of the abnormal region (lesion) of the mucous membrane to which the composition for photodynamic therapy of the present invention is attached may be specified. This is preferable because the risk of light irradiation other than the part to which the composition for photodynamic therapy of the present invention is attached in the abnormal region (lesion) of the mucous membrane is reduced.
  • the light source device 13 is activated, emits white light or bluish light from the illumination windows 22a and 22b, and irradiates the observed portion in the subject.
  • a video signal from the imaging device is input to the arithmetic / control device 12, and the arithmetic / control device 12 is a portion of the abnormal region (lesion) of the mucous membrane of the subject to which the composition for photodynamic therapy of the present invention is attached. Specify the position of.
  • the arithmetic / control device 12 transmits a control signal to the light source device 13, and the light from the light source device 13 passes through the illumination windows 22a and 22b, and the composition for photodynamic therapy of the present invention on the mucous membrane of the subject.
  • the irradiated light is white light, LED light having a wavelength of 660 ⁇ 10 nm, or laser light. This light excites methylene blue contained in the composition for photodynamic therapy of the present invention to sterilize abnormal areas (lesions) of the mucosa.
  • composition for photodynamic therapy for treating mucocutaneous infection contains methylene blue and has a pH of 7.6 to 9.5.
  • a mucocutaneous infection is an infection of the skin or mucous membrane caused by pathogenic microorganisms. Neither skin nor mucous membrane is particularly limited. Examples of the mucous membrane include oral mucosa, esophageal mucosa, gastric mucosa, intestinal mucosa, nostril, lips, ears, genital organs, and anus.
  • pathogenic microorganisms for mucocutaneous infection include Staphylococcus aureus, MRSA (Methicillin Resistant Staphylococcus aureus), Streptococcus sp., Mycobacteria Includes Gram-positive bacteria such as Mycobacterium sp., Gram-negative bacteria such as Pseudomonas aeruginosa, Escherichia coli, and Treponema sp.
  • Pathogenic bacteria including Candida albicans, Candida sp., Cryptococcus neoformans, Cryptococcus sp., Malassezia pachydermatis, and Malassezia pachydermatis Diseases such as (Malassezia sp.) Examples include protozoan fungi, parasites such as striatum, amoeba such as acanthamoeba, and viruses having an envelope such as herpes simplex virus.
  • the pathogenic microorganism is preferably at least one selected from the group consisting of Candida albicans, MRSA (Methicillin Resistant Staphylococcus aureus), Pseudomonas aeruginosa, and Escherichia coli.
  • the methylene blue (3,7-bis (dimethylamino) phenothiazinium chloride) contained in the photodynamic therapy composition for treating dermal mucosal infection of the present invention is not particularly limited. It may be a hydrate. Examples of the hydrate include, but are not limited to, dihydrate, trihydrate, and tetrahydrate.
  • methylene blue may be sold as a pharmaceutical or may be sold as a reagent. A reagent having a high purity is preferable, and for example, a reagent specified in JIS K 8897: 2012 is more preferable.
  • Methylene blue is safe for the human body to be used for staining during chromoendoscopy of the gastrointestinal tract, intravenously or orally administered in the treatment of drug-induced methemoglobinemia, treatment of ifosfamide encephalopathy It has been established because it is used by intravenous injection. It is low toxic to animals other than humans, and the safety of methylene blue has been established.
  • the concentration of methylene blue when the composition for photodynamic therapy for treating dermal mucosal infection of the present invention is contacted with a pathogenic microorganism is not particularly limited, but is preferably 0.0007 to 4.0 w / v%, more preferably Is 0.001 to 3.0 w / v%, more preferably 0.003 to 2.0 w / v%, still more preferably 0.005 to 1.0 w / v%, and still more preferably 0.007 to 0. 80 w / v%.
  • the antibacterial activity against pathogenic microorganisms is further improved.
  • the lowest digit of the concentration is rounded off by one digit below that. For example, “0.001” includes 0.00095 or more and less than 0.0015, and “4.0” includes 3.95 or more and less than 4.05.
  • the pH of the composition when the composition for photodynamic therapy for treating mucocutaneous infection of the present invention is contacted with a pathogenic microorganism is 7.6 to 9.5, preferably 8.3 to 9. 2, more preferably 8.5 to 9.0.
  • the pH when the composition for photodynamic therapy for treating a mucocutaneous infection of the present invention is brought into contact with a pathogenic microorganism of the mucocutaneous infection is within this range, the antibacterial activity against the pathogenic microorganism is excellent.
  • pH is rounded off to the second decimal place.
  • “7.6” includes 7.55 or more and less than 7.65
  • “9.5” includes 9.45 or more and less than 9.55.
  • pH was measured with a pH meter using a glass electrode specified in JIS Z 8802: 2011 “pH measurement method”. 25 PH value at ° C.
  • the method for adjusting the pH of the composition for photodynamic therapy for treating the mucocutaneous infection of the present invention is not particularly limited, and examples thereof include a method of adding a pH adjuster.
  • a pH adjuster those having low toxicity to humans or animals other than humans are preferable.
  • citric acid, gluconic acid, succinic acid, lactic acid, sodium hydrogen carbonate (also referred to as “bicarbonate”) examples thereof include sodium carbonate, potassium carbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium dihydrogen phosphate, and disodium hydrogen phosphate.
  • sodium bicarbonate is particularly preferred.
  • sodium hydrogen carbonate When sodium hydrogen carbonate is used as a pH adjuster, the antibacterial activity is further improved.
  • sodium bicarbonate is used as a pH adjuster and when potassium dihydrogen phosphate (KH 2 PO 4 ) and disodium hydrogen phosphate (Na 2 HPO 4 ) are used, the same pH is obtained. Even so, the use of sodium hydrogen carbonate shows superior antibacterial activity.
  • potassium dihydrogen phosphate (KH 2 PO 4 ) and disodium hydrogen phosphate (Na 2 HPO 4 ) the same pH is obtained. Even so, the use of sodium hydrogen carbonate shows superior antibacterial activity.
  • KH 2 PO 4 potassium dihydrogen phosphate
  • Na 2 HPO 4 disodium hydrogen phosphate
  • the addition amount of the pH adjuster is not particularly limited as long as the pH of the composition for photodynamic therapy for treating the mucocutaneous infection of the present invention is within the above-described pH range.
  • sodium bicarbonate sodium bicarbonate
  • the concentration cannot be generally stated, but is preferably, for example, 0.007 to 0.80 w / v%, more preferably 0.01 to 0.70 w / v%, more preferably 0.05 to 0.55 w / v%, still more preferably 0.07 to 0.50 w / v%, still more preferably 0.10 to 0.40 w. / V%.
  • the antibacterial activity against pathogenic microorganisms of dermal mucosal infection is further improved.
  • composition for photodynamic therapy for treating mucocutaneous infection of the present invention may further contain a pharmaceutically acceptable additive.
  • Pharmaceutically acceptable additives include pH adjusters, buffers, wetting agents / solubilizers, antibacterial preservatives, chelating agents, complexing agents, antioxidants, sweeteners, and excipients other than those mentioned above Agents, binders, disintegrants, lubricants, fluidizers / anti-caking agents, and suspending agents / adhesives. These additives can be included in the composition for photodynamic therapy for treating H. pylori infections of the present invention alone or in combination of two or more.
  • the photodynamic therapy composition for treating dermal mucosal infection of the present invention may further comprise liposomes, nanoparticles, colloidal suspensions, micelles, microemulsions, vesicles and nanospheres.
  • the photodynamic therapy composition for treating dermal mucosal infections of the present invention may also contain further components, such as conventionally known delivery vehicles and excipients, which may include solvents such as alcohol ( For example, ethanol, polyethylene glycol, glycerol or n-butanol), dimethyl sulfoxide, water, saline, solubilizer, pH adjuster, gelling agent, thickener, buffer and combinations thereof.
  • the composition for photodynamic therapy for treating mucocutaneous infection of the present invention may be a dry composition that can be reconstituted before use, or is in the form of a prefill that is pre-sterilized and sealed. Also good.
  • methylene blue and, if desired, a pH adjuster may be aseptically dissolved in pure water or physiological saline and aseptically filled into a syringe having a tube at the tip.
  • composition for photodynamic therapy for treating a mucocutaneous infection of the present invention is preferably brought into contact with a pathogenic microorganism present in a lesion of a mucocutaneous infection and irradiated with light to the skin. Used in photodynamic therapy to treat mucosal infections.
  • composition for photodynamic therapy for treating dermal mucosal infection of the present invention can also be used as an antibacterial agent, antifungal agent or antiviral agent.
  • photodynamic therapy compositions for treating mucocutaneous infections of the present invention include use as antimicrobial and antifungal treatments for skin and wound infections such as burns; parasitic infections, gastric infections, Use for malaria, leprosy; Use for bacterial and fungal spore inactivation; Use for prion and viral infections, eg treatment of HIV; Use for ear, nose and throat infection, tuberculosis; Sexual infection Use for treatment of local infections of the hair, nails and epidermis, such as foot and body tinea and genital candidiasis; and infection prevention agents such as surgical wounds Use for sterilization, skin sterilization, stem cell sterilization, graft-versus-host rejection disease; skin diseases such as psoriasis, acne, vitiligo and eczema and other skin conditions such as multiple Use for infectious and sunburn damage, other benign
  • the administration form of the composition for photodynamic therapy for treating the mucocutaneous infection of the present invention is not particularly limited, but for example, intravenous administration, oral administration, transdermal administration, transmucosal administration, muscle Internal administration etc. are mentioned, Preferably it is local administration.
  • a method of administering by direct spraying to the lesion part of the upper gastrointestinal tract or the lower gastrointestinal tract through an endoscope can be mentioned.
  • methylene blue and, if necessary, a pH adjusting agent are dissolved in pure water or physiological saline and filled into a syringe having a tube at the tip, and the tube is inserted into the forceps port of the endoscope.
  • the drug can be sprayed onto the stomach wall by pressing.
  • the composition When administered topically, the composition is delivered via various means, for example via sprays, lotions, suspensions, emulsions, gels, ointments, salves, sticks, soaps, liquid aerosols, powder aerosols, drops or pastes. can do.
  • the method for producing the composition for photodynamic therapy for treating mucocutaneous infection of the present invention is not particularly limited.
  • methylene blue is dissolved in water to produce a methylene blue solution having a desired concentration. Can do. If the pH of the methylene blue solution is not within the range of 7.6 to 9.5, a pH adjuster is added to adjust the pH within the range of 7.6 to 9.5.
  • methylene blue can be dissolved in water or ethanol to prepare a stock solution having a concentration of about 1.0 to 5.0 w / v%, and this stock solution can be diluted with water to produce a methylene blue solution having a desired concentration. Good. Commercially available products may be used as the methylene blue stock solution.
  • Such stock solutions include methylene blue stock solution (manufactured by Kishida Chemical Co., Ltd .; ethanol solution, concentration 5.0 w / v%). .
  • physiological saline sodium chloride concentration: 0.9 w / v%)
  • sterilized purified water sterilized purified water
  • distilled water and the like can be used.
  • the photodynamic therapy composition for treating a mucocutaneous infection of the present invention and one or more pharmaceutically acceptable carriers are mixed at a suitable temperature and a suitable pH.
  • the composition for photodynamic therapy for treating mucocutaneous infection of the present invention can be used for humans and can also be used for animals other than humans.
  • non-human animals include, without limitation, non-human mammals including monkeys, cats, pigs, dogs and the like.
  • animals other than humans include, but are not limited to, vertebrates other than mammals such as birds, reptiles, amphibians, and fish.
  • non-human animals include domestic animals such as dogs, cats, cows, horses, pigs, sheep, goats, donkeys, camels, etc., dogs, cats, foxes, raccoons, monkeys, donkeys, horses, etc.
  • pets include, but are not limited to.
  • the composition for photodynamic therapy for treating skin mucosal infection of the present invention can be applied according to the dosage form.
  • the composition for photodynamic therapy for treating mucocutaneous infection described above is applied to a lesion of mucocutaneous infection and white light or an LED having a wavelength of 660 ⁇ 10 nm is applied. Irradiate light or laser light. The application and / or light irradiation is preferably performed endoscopically.
  • Transendoscopically is used to mean “using an endoscope”.
  • pathogenic microorganisms that infect mucosa such as esophagus, duodenum, small intestine, large intestine, pharynx, bronchi, etc.
  • photodynamic therapy for treating mucocutaneous infection of the present invention by performing endoscopically
  • the composition can be more reliably applied to the lesioned part of the dermal mucosal infection, and can be applied to the non-lesioned part as much as possible.
  • Differentiation of lesioned and non-lesioned parts includes a method that utilizes the tendency of redness in the lesioned part. This method has an advantage that the load on the skin mucous membrane is extremely small because the lesioned part and the non-lesioned part can be differentiated by image processing.
  • the light to be irradiated is white light, LED light having a wavelength of 660 ⁇ 10 nm, or laser light.
  • the light source is not particularly limited as long as it can emit white light or light having the above wavelength.
  • the light source may be a coherent light source or an incoherent light source.
  • the coherent light source include a laser and a laser diode, and an AlGaInP (aluminum gallium indium phosphide) quantum well laser diode or an aluminum gallium arsenide laser having a wavelength of 660 nm is particularly preferable.
  • Examples of incoherent light sources include LEDs (Light Emitting Diodes), incandescent lamps, fluorescent lamps, and xenon lamps.
  • the white light white light that is usually used for observation can be used.
  • the white light may be white light obtained by combining blue laser light having a wavelength of 445 nm and fluorescence excited and emitted from the phosphor by the blue laser light.
  • the phosphors are a plurality of kinds of phosphors that absorb a part of blue laser light and emit light with excitation from green to yellow (for example, YAG (yttrium, aluminum, garnet) phosphors, BAM (barium / aluminum)). It is preferable to use a material including an oxide (phosphor such as BaMgAl 10 O 17 : Eu 2+ ).
  • the light projection amount is not particularly limited, but is preferably 1 to 200 J / m 2 , more preferably 1 to 100 J / m 2 , and further preferably 5 to 100 J / m 2 , and more It is preferably 3 to 30 J / m 2 , and more preferably 5 to 15 J / m 2 . Within this range, a safer and higher sterilizing effect can be expected.
  • the light irradiation time is not particularly limited and can be appropriately set so as to be the above light projection amount. However, for example, it is preferably 30 to 600 seconds, more preferably 30 to 300 seconds, and still more preferably 60. It is ⁇ 300 seconds, more preferably 80 to 240 seconds.
  • the composition for photodynamic therapy for treating dermal mucosal infection of the present invention can exhibit sufficient antibacterial activity even at a relatively low light projection amount. For example, even a 1400 lux white light source used for normal observation shows antibacterial activity.
  • the method for treating mucocutaneous infection of the present invention can be applied to humans as well as animals other than humans.
  • non-human animals include, without limitation, non-human mammals including monkeys, cats, pigs, dogs and the like.
  • animals other than humans include, but are not limited to, vertebrates other than mammals such as birds, reptiles, amphibians, and fish.
  • non-human animals include domestic animals such as dogs, cats, cows, horses, pigs, sheep, goats, donkeys, camels, etc., dogs, cats, foxes, raccoons, monkeys, donkeys, horses, etc.
  • pets include, but are not limited to.
  • the present invention relates to a sterilization system for lesions caused by skin mucosal infection (hereinafter sometimes simply referred to as “the skin mucosa sterilization system of the present invention”) and a method for operating a sterilization system for lesions caused by skin mucosal infection (hereinafter referred to as “mucosal mucosa infection system”).
  • the skin mucosa sterilization system of the present invention a sterilization system for lesions caused by skin mucosal infection
  • mucosal mucosa infection system simply referred to as “mucosal mucosa infection system”.
  • the skin mucosa sterilization system of the present invention will be described below with reference to the drawings as appropriate.
  • the composition for photodynamic therapy for treating a mucocutaneous infection of the present invention may be referred to as “the composition for photodynamic therapy of the present invention”.
  • the skin mucous membrane sterilization system of the present invention includes a sterilization system 100 shown in FIG.
  • the sterilization system 100 includes a calculation / control unit 101, an imaging unit 102, an imaging direction control unit 103, a light irradiation unit 104, an irradiation direction control unit 105, and a composition injection unit 106.
  • the injection direction control means 107 and the transmission paths 108 to 113 are provided.
  • the image pickup means 102 includes an image pickup optical system 102a including an image pickup device (not shown) for picking up an observation region, a signal processing unit for performing analog / digital conversion processing of a video signal from the image pickup device, and an arithmetic / control unit 101. With an interface.
  • the imaging unit 102 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the imaging unit 102 and the calculation / control unit 101 via the transmission path 108.
  • the image sensor is a color image sensor, which captures a reflected image to be photographed and outputs a video signal.
  • the imaging element is preferably a CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal-Oxide Semiconductor: complementary metal oxide semiconductor) image sensor.
  • the imaging direction control means 103 includes a drive mechanism for changing the imaging direction of the imaging means 102 and an interface with the calculation / control unit 101.
  • the imaging direction control means 103 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the imaging direction control unit 103 and the calculation / control unit 101 via the transmission path 109.
  • the light irradiation unit 104 includes an illumination optical system 104a that emits illumination light and / or excitation light, a light source unit that supplies light to the illumination optical system 104a, and an interface with the calculation / control unit 101.
  • the light irradiation unit 104 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the light irradiation unit 104 and the calculation / control unit 101 via the transmission path 110.
  • the light irradiation means 104 may be an integrated type in which the illumination optical system 104a and the light source unit are built in the same housing, or a separate type in which the illumination optical system 104a and the light source unit are built in separate housings. It may be.
  • the illumination light and / or excitation light emitted by the light irradiation means 104 can be appropriately selected depending on the application.
  • white light, daylight white light, daylight color light, light bulb color light, or the like is usually used as light for illuminating the observation region.
  • white light is preferable because a natural color tone of the observation region can be obtained.
  • light that emphasizes the color difference is used. It is preferable.
  • the excitation light for the composition for photodynamic therapy of the present invention it is preferable to irradiate white light, LED light having a wavelength of 660 ⁇ 10 nm, or laser light because methylene blue can be efficiently excited.
  • the irradiation direction control unit 105 includes a drive mechanism for changing the irradiation direction of the light irradiation unit 104 and an interface with the calculation / control unit 101.
  • the irradiation direction control means 105 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the irradiation direction control unit 105 and the calculation / control unit 101 via the transmission path 111.
  • the composition injection means 106 includes an injection unit 106a having an opening for injecting the photodynamic therapy composition of the present invention, a liquid supply tank (not shown) in which the photodynamic therapy composition of the present invention is stored, The liquid feed pump (not shown) for injecting the composition for photodynamic therapy of the present invention and an interface with the calculation / control unit 101 are provided.
  • the composition injection unit 106 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the composition injection unit 106 and the calculation / control unit 101 via the transmission path 112.
  • the composition injection means 106 may be an integrated type in which the injection unit 106a, the liquid supply tank, and the liquid supply pump are built in the same housing, or only the liquid supply tank may be disposed outside.
  • the liquid feeding tank and the liquid feeding pump may be arranged outside, and the liquid feeding tank and the liquid feeding pump may be separated.
  • the opening of the injection unit 106a may be a simple hole or a nozzle capable of spraying the composition for photodynamic therapy of the present invention in a spray form.
  • the injection direction control unit 107 includes a drive mechanism for changing the injection direction of the injection direction control unit 107 and an interface with the calculation / control unit 101.
  • the injection direction control means 107 is controlled based on a control signal from the calculation / control unit 101. Communication is performed between the ejection direction control means 107 and the calculation / control unit 101 via the transmission path 113.
  • the transmission paths 108 to 113 may be wired or wireless. In the case of a wired connection, either a metal cable or an optical cable may be used.
  • the imaging direction control unit 103 When the imaging unit 102, the light irradiation unit 104, and the composition ejecting unit 106 move together, the imaging direction control unit 103, the irradiation direction control unit 105, and the ejection direction control unit 107 are integrated into one direction control unit. It may be.
  • the composition for photodynamic therapy for treating mucocutaneous infection of the present invention may be referred to as “the composition for photodynamic therapy of the present invention”. is there.
  • the imaging direction control unit 103 and the irradiation direction control unit 105 are operated based on a control signal from the calculation / control unit 101 so that the light irradiation unit 104 illuminates the observation region of the imaging unit 102.
  • the imaging unit 102 images the skin or mucous membrane 200 based on the control signal from the calculation / control unit 101 and transmits a video signal to the calculation / control unit 101.
  • the calculation / control unit 101 receives the video signal transmitted from the imaging unit 102, performs video processing so as to emphasize the color difference between the normal region and the abnormal region of the mucous membrane, and the normal unit 201 and the lesion
  • the part 202 is identified, and the position of the lesioned part 202 is specified.
  • the injection direction control means 107 is operated based on a control signal from the calculation / control unit 101 so that the injection direction of the composition injection means 106 is matched with the lesioned part 202.
  • the composition ejecting means 106 ejects the composition for photodynamic therapy of the present invention based on the control signal from the calculation / control unit 101.
  • the irradiation direction control unit 105 is operated based on a control signal from the calculation / control unit 101 so that the irradiation direction of the light irradiation unit 104 is aligned with the lesioned part 202.
  • the light irradiation means 104 emits white light, LED light having a wavelength of 660 ⁇ 10 nm or laser light based on a control signal from the calculation / control unit 101.
  • light irradiation to the composition for photodynamic therapy is performed as follows instead of (f) and (g) above.
  • (F1) to (g1) may be used.
  • the imaging direction control unit 103 and the irradiation direction control unit 105 are operated based on a control signal from the calculation / control unit 101 so that the light irradiation unit 104 illuminates the observation region of the imaging unit 102.
  • the imaging unit 102 images the skin or mucous membrane 200 based on the control signal from the calculation / control unit 101 and transmits a video signal to the calculation / control unit 101.
  • the calculation / control unit 101 receives the video signal transmitted from the imaging means 102, identifies the normal region and the abnormal region of the mucous membrane, and identifies the presence or absence of adhesion of the photodynamic therapy composition of the present invention. Image processing is performed so as to be able to be performed, and the position of the region where the lesioned part 202 and the attachment part 203 of the composition for photodynamic therapy overlap is specified. (f4) Irradiation direction control means based on a control signal from the calculation / control unit 101 so that the irradiation direction of the light irradiation means 104 matches the region where the lesioned part 202 and the photodynamic therapy composition attachment part 203 overlap. 105 is activated. (g1) The light irradiation unit 104 emits white light, LED light having a wavelength of 660 ⁇ 10 nm, or laser light based on a control signal from the calculation / control unit 101.
  • the sterilization system 10 shown in FIG. 2 includes an endoscope 11, a calculation / control device 12, a light source device 13, an air / water supply device 14, and a liquid supply device 15.
  • the air / water supply device 14 is built in the light source device 13 and is provided outside the light source device 13 and a known air supply pump 14a that generates a delivery pressure of fluid such as air and cleaning water, and stores cleaning water.
  • the cleaning water tank 14b is constituted.
  • the difference from conventional electron microscope systems is that, generally speaking, the calculation / control device 12 shown in FIG.
  • the liquid processing device 15 can supply the composition for photodynamic therapy of the present invention to the endoscope 11, and the endoscope 11 has a video processing unit that identifies the position of the abnormal part.
  • a point that can be discharged from the WJ outlet 24 (see FIGS. 3A and 3B) provided at the distal end portion 16a toward the lesioned portion of the mucous membrane, and illumination windows 22a and 22b provided at the distal end portion 16a of the endoscope 11 ( 3A and FIG. 3B) that white light or LED light or laser light having a wavelength of 660 ⁇ 10 nm can be irradiated to a mucosal lesion or an area where the composition for photodynamic therapy of the present invention is attached. It is in
  • the endoscope 11 shown in FIG. 2 includes an insertion unit 16 to be inserted into a subject, an operation unit 17 connected to a proximal end (rear end) portion of the insertion unit 16, an arithmetic / control device 12, And a universal cord 18 connected to the light source device 13.
  • the insertion portion 16 shown in FIG. 2 is provided at the distal end thereof, and is connected to a distal end portion 16a in which an imaging element (not shown) for in-subject imaging is incorporated, and a proximal end of the distal end portion 16a.
  • the portion 16a is rotatably supported and includes a bendable bendable portion 16b and a flexible flexible tube portion 16c that is connected to the base end of the bendable portion 16b.
  • a tip cap 20 shown in FIGS. 3A and 3B is attached to the tip of the tip portion 16a shown in FIG.
  • the tip cap 20 is provided with an observation window 21, illumination windows 22a and 22b, and a forceps outlet 23 from which the tip of the forceps protrudes.
  • the tip cap 20 has a composition for photodynamic therapy of the present invention, washing water, a chemical solution, and the like for a portion to be observed in the subject (hereinafter sometimes referred to as “observed portion”).
  • a water jet outlet (hereinafter sometimes referred to as “WJ outlet”) 24 for jetting a liquid and an jet nozzle 25 for jetting air or washing water toward the observation window 21 are provided.
  • the observation window 21 is formed in front of the image sensor and allows photographing light incident on the image sensor to pass therethrough.
  • Two illumination windows 22a and 22b are arranged at symmetrical positions with respect to the observation window 21, and irradiate the observation part in the subject with the illumination light from the light source device 13.
  • the forceps outlet 23 shown in FIGS. 3A and 3B communicates with a forceps inlet 26 provided in the operation unit 17 shown in FIG.
  • Various kinds of treatment tools having an injection needle, a high-frequency knife or the like arranged at the tip are inserted into the forceps inlet 26.
  • an air / water button 30 for feeding cleaning water may be provided.
  • the air / water supply button 30 is operated so as to supply air
  • the air supplied from the air supply pump 14 a is sent to the endoscope 11.
  • the air / water supply button 30 is operated so as to perform water supply, the air supplied from the air supply pump 14a is sent to the wash water tank 14b, and the wash water is supplied from the wash water tank 14b by this air pressure. And sent to the endoscope 11.
  • the operation portion 17 receives a control signal from the arithmetic / control device 12, and drives the bending portion up / down bending mechanism and / or the bending portion left / right bending mechanism built in the endoscope 11. Then, the bending portion 16b is bent up and down / left and right.
  • the air supply pump 14a receives a control signal from the arithmetic / control device 12, and the air supply pump 14a operates to supply air to the endoscope 11.
  • the supplied air is sent to the endoscope 11.
  • the air supply pump 14a receives a control signal from the arithmetic / control device 12, operates so that the air supply pump 14a supplies air to the cleaning water tank 14b, and supplies air from the air supply pump 14a.
  • the air that has been aired is sent to the washing water tank 14 b, and the washing water is sent from the washing water tank 14 b by this air pressure and sent to the endoscope 11.
  • the operation unit 17 may be provided with a mode switch 27 and a zoom operation unit 31 in addition.
  • the mode changeover switch 27 is used for a switching operation between two types of modes, a normal observation mode and a special observation mode.
  • the normal observation mode is a mode in which white light is used for illumination of the observation area.
  • the special observation mode is a mode that uses bluish light to illuminate the area to be observed, and emphasizes changes in the color of the mucous membrane and blood see-through to distinguish between normal and abnormal areas of the mucosa This mode makes it easy to distinguish.
  • the zoom operation unit 31 is used for a zoom operation for driving the zooming mechanism in the endoscope 11 to enlarge or reduce the observation image. In the normal observation mode, daylight white light, daylight color light, light bulb color light, or the like may be used instead of white light, and in the special observation mode, white light may be used instead of the special light.
  • a connector 32 is attached to one end of the universal cord 18 shown in FIG.
  • the connector 32 is a composite type connector and is connected to the calculation / control device 12, the light source device 13, and the liquid feeding device 15, respectively.
  • the arithmetic / control apparatus 12 shown in FIG. 2 performs various video processes on the video signal input from the image sensor via the universal code 18 and the connector 32, and generates an endoscopic image.
  • the endoscopic image generated by the arithmetic / control device 12 is displayed on a monitor 33 connected to the arithmetic / control device 12 by a cable.
  • the arithmetic / control device 12 is connected to the light source device 13 via a communication cable, and communicates various control information with the light source device 13.
  • the liquid delivery device 15 shown in FIG. 2 includes a composition for photodynamic therapy according to the present invention, washing water or washing liquid for washing the inside of a subject, or a liquid feeding tank 35 in which a chemical solution is stored, a motor and a control circuit. And a liquid feed pump 37 that is disposed on the front surface of the liquid feed body 36 and that feeds the cleaning liquid stored in the liquid feed tank 35.
  • the liquid feeding device 15 includes a liquid feeding pipe 39 that connects the liquid feeding pump 37 and the connector 32, and a connecting pipe 40 that connects the liquid feeding tank 35 and the liquid feeding pump.
  • the liquid feeding device 15 may include a foot switch 38 for operating the liquid feeding pump 37 to perform a liquid feeding operation. Instead of the foot switch 38, a manually operable switch or a remote controller may be used.
  • the liquid delivery device 15 normally operates based on a control signal from the arithmetic / control device 12.
  • the light guides 41 a and 41 b have one end fixed to the tip cap 20 and the other end connected to the light source device 13 via the universal cord 18 and the connector 32.
  • An illumination optical system (not shown) including an illumination lens (not shown) is incorporated behind the illumination windows 22a and 22b.
  • the light guides 41a and 41b have their emission ends facing illumination lenses disposed behind the illumination windows 22a and 22b, and guide the light from the light source device 13 to the illumination windows 22a and 22b.
  • One end of the forceps tube 42 is fixed to the tip cap 20 and connected to the forceps outlet 23, and the other end is connected to the forceps inlet 26 through the inside of the bending portion 16 b, the flexible tube portion 16 c, the operation portion 17, and the like.
  • the forceps outlet 23 and the forceps inlet 26 communicate with each other.
  • One end of the air / water supply tube 43 is connected to the injection nozzle 25, and the other end is connected to the air / water supply device 14 via the universal cord 18 and the connector 32.
  • the air / water supply tube 43 sends the air and the wash water supplied from the air / water supply device 14 to the injection nozzle 25.
  • the injection nozzle 25 injects air and cleaning water supplied from the air / water supply device 14 toward the observation window 21 to wipe away dirt adhering to the observation window 21.
  • the multi-core cable 44 electrically connects the arithmetic / control device 12 and the image sensor.
  • the multi-core cable 44 includes a plurality of signal cables 44a, and the plurality of signal cables 44a are covered with an outer cover 44b that functions as an electric shield layer.
  • the flexible tube portion 16c includes a screw tube 51 called a flex that protects the inside while maintaining flexibility in order from the inside, and a net 52 called a blade that covers the screw tube 51 and prevents the screw tube 51 from extending. And a flexible rubber 53 covered on the net 52.
  • the outer layer of the curved portion 16 b is also composed of rubber 53.
  • the WJ tube 45 includes a soft rubber WJ soft tube (not shown) that passes through the curved portion 16b and the flexible tube portion 16c, and a hard metal WJ that passes through the tip portion 16a. It consists of a hard tube (not shown), and the photodynamic therapy composition, cleaning solution or chemical solution of the present invention fed by the solution feeding device 15 is sent to the WJ outlet 24.
  • One end of the WJ soft tube passes through the operation unit 17 and is connected to the liquid feeding device 15 via the universal cord 18, the connector 32, and the liquid feeding pipe 39. The other end of the WJ soft tube is connected to the WJ hard tube.
  • the WJ hard tube (not shown) extends in the photographic optical axis direction, and its distal end is bent in a direction substantially perpendicular to the photographic optical axis direction, and an image sensor (not shown) is formed in the radial direction of the distal end portion 16a.
  • a first WJ path (not shown) extending in the photographic optical axis direction at a position away from the optical axis), one end communicating with the WJ outlet 24, and the other end extending in a direction substantially perpendicular to the photographic optical axis direction.
  • a second WJ path 47b in communication.
  • the first WJ path is connected to a WJ soft tube (not shown).
  • the second WJ path is linearly formed on the orthogonal plane orthogonal to the photographing optical axis.
  • the second WJ path may be bent or curved. Also good.
  • the tip end portion 16a is made of a metal cylindrical tip portion main body (not shown) and a metal tip pipe (not shown) covering the tip portion main body.
  • the WJ hard tube (not shown) is fixed to the tip body with the tip inserted into the tip body.
  • the light guides 41a and 41b, the forceps tube 42, and the air / water supply tube 43 are also fixed to the distal end portion main body in a state where the distal end portions are inserted into the distal end portion main body.
  • the distal end pipe has an outer peripheral surface covered with rubber 53, and a distal end cap 20 is attached to the distal end portion.
  • an imaging optical system including an imaging lens (not shown) and an imaging element (not shown) is arranged.
  • the imaging optical system is fixed to a tip body (not shown).
  • the imaging device is preferably a CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal-Oxide Semiconductor) image sensor.
  • the imaging optical system makes the image light of the observation part incident from the observation window 21 enter the imaging lens, and the imaging lens forms an image on the imaging surface of the imaging element.
  • the calculation / control device 12 and the light source device 13 are turned on, and the insertion portion 16 of the endoscope 11 is inserted into the subject.
  • the light from the light source device 13 is irradiated to the observation part in the subject through the light guides 41a and 41b, the illumination optical system (not shown), and the illumination windows 22a and 22b.
  • the light may be white light, but bluish light may be used in order to emphasize the color difference between the normal area and the abnormal area (lesioned area) of the mucous membrane.
  • An imaging element (not shown) built in the distal end portion 16a of the insertion portion 16 images the inside of the subject and outputs a video signal.
  • This video signal is input to the arithmetic / control device 12 via the universal cord 18 and the connector 32.
  • the arithmetic / control device 12 performs image processing that emphasizes the color difference between the normal area and abnormal area (lesion) of the mucous membrane, and identifies the position of the abnormal area (lesion area) of the mucosa based on the color difference. To do. Further, the arithmetic / control device 12 can perform various video processes on the input video signal to generate an image in the subject, and display the image in the subject on the monitor 33.
  • the calculation / control device 12 When observing the inside of the subject, the calculation / control device 12 outputs a control signal to the operation unit 17 so as to bend the bending portion 16b in the vertical direction and the horizontal direction.
  • This control signal is input to the operation unit 17 via the universal cord 18 and the connector 32, and the operation unit 17 operates the bending portion up-and-down bending mechanism and the bending portion right and left bending mechanism built in the endoscope 11, so that the distal end The direction of the part 16a is changed, and different places of the mucous membrane in the subject are observed.
  • the calculation / control device 12 gives an instruction to the operator, and the operation unit 17 is bent up and down.
  • the angle knob 28 for bending and / or the angle knob 29 for bending left and right may be operated to bend the bending portion 16b in the vertical direction and the horizontal direction.
  • the calculation / control device 12 When the calculation / control device 12 specifies the position of the abnormal region (lesion) in the mucous membrane of the subject, the calculation / control device 12 transmits a control signal to the operation unit 17 to bend the bending portion 16b. The jet direction of the WJ outlet 24 is adjusted to the abnormal region (lesioned portion). Then, a control signal is transmitted to the liquid delivery device 15, the liquid delivery pump 37 is operated, and the composition for photodynamic therapy of the present invention stored in the liquid delivery tank 35 is connected to the connecting tube 40, the liquid delivery pump 37, It is sent to the WJ tube via the liquid feed pipe 39 and the connector 32.
  • composition for photodynamic therapy of the present invention sent to the WJ tube is ejected from the WJ outlet 24 through the WJ soft tube and the WJ hard tube, and includes at least a part of an abnormal region (lesion) of the mucous membrane. Adhere to.
  • the arithmetic / control device 12 transmits a control signal to the light source device 13, and the light from the light source device 13 passes through the light guides 41a and 41b, the illumination optical system (not shown), and the illumination windows 22a and 22b. Then, irradiation is performed toward the region of the mucous membrane of the subject to which the composition for photodynamic therapy of the present invention is attached.
  • the irradiated light is white light, LED light having a wavelength of 660 ⁇ 10 nm, or laser light.
  • the position of the part of the abnormal region (lesion) of the mucous membrane to which the composition for photodynamic therapy of the present invention is attached may be specified. This is preferable because the risk of light irradiation other than the part to which the composition for photodynamic therapy of the present invention is attached in the abnormal region (lesion) of the mucosa is reduced.
  • the light source device 13 is activated, emits white light or bluish light from the illumination windows 22a and 22b, and irradiates the observed portion in the subject.
  • a video signal from the imaging device is input to the arithmetic / control device 12, and the arithmetic / control device 12 is a portion of the abnormal region (lesion) of the mucous membrane of the subject to which the composition for photodynamic therapy of the present invention is attached. Specify the position of.
  • the arithmetic / control device 12 transmits a control signal to the light source device 13, and the light from the light source device 13 passes through the illumination windows 22a and 22b, and the composition for photodynamic therapy of the present invention on the mucous membrane of the subject.
  • the irradiated light is white light, LED light having a wavelength of 660 ⁇ 10 nm, or laser light. This light excites methylene blue contained in the composition for photodynamic therapy of the present invention to sterilize abnormal areas (lesions) of the mucosa.
  • Example 1 ⁇ Antimicrobial activity test against Helicobacter pylori> (1) Acquisition of Helicobacter pylori Helicobacter pylori JCM 12093 strain was purchased from the Bioresource Center of RIKEN (JCM: Japan Collection of Microorganisms).
  • 0.20 mL, 1.0 mL, 2.0 mL, 4.0 mL, 10.0 mL, and 20.0 mL of the prepared 5.0 w / v% methylene blue aqueous solution are weighed and transferred to 100 mL volumetric flasks, respectively.
  • the methylene blue concentration is 0.01 w / v%, 0.05 w / v%, 0.10 w / v%, 0.20 w / v%, 0.50 w / v%, and 1. 100 mL of 0 w / v% methylene blue aqueous solution was prepared.
  • Antibacterial activity test 130 mL of the antibacterial activity test sample was added to a Helicobacter agar medium (manufactured by Nissui Pharmaceutical Co., Ltd.), and evenly applied to the medium with a congeal bar, and left in the dark for 5 minutes.
  • LED light beam projector amount (wavelength 660 nm) is 0J / m 2, 5J / m 2, 10J / m 2 or 15J / m 2,, and the light irradiation so.
  • the light projection amount of 0 J / m 2 means that no light irradiation was performed.
  • the cells were cultured for 4 days at 37 ° C. in an incubator.
  • the blank sample was not irradiated with light.
  • a blank sample that was not irradiated with light was used as a blank. After culturing for 4 days, the number of viable colonies in each medium was counted, and compared with the blank, antibacterial activity was evaluated according to the following criteria.
  • the methylene blue concentration [w / v%], sodium bicarbonate concentration [w / v%] and pH of the antibacterial activity test sample are set in the “antibacterial activity test”.
  • the column shows the evaluation results of antibacterial activity.
  • Example 2 ⁇ Antimicrobial activity test against Candida> (1) Obtaining Candida Candida albicans was purchased from a strain distribution agency.
  • Candida suspension (bacterial solution)
  • Candida albicans was cultured, the obtained culture was suspended in sterile physiological saline, the number of bacteria was adjusted, and a bacterial solution was prepared.
  • sample Methylene blue solution 10.0 mL, sodium hydrogen carbonate aqueous solution 1.0 mL, and bacterial solution 2.0 mL were mixed, and methylene blue shown in the column of “Composition for photodynamic therapy” in Table 2 Samples for antibacterial activity testing of concentration, sodium bicarbonate concentration, and pH were prepared. In addition, a blank sample was prepared by mixing 11.0 mL of physiological saline and 2.0 mL of bacterial solution.
  • Antibacterial activity test was conducted in the same manner as in Example 1.
  • the methylene blue concentration [w / v%], sodium bicarbonate concentration [w / v%] and pH of the antibacterial activity test sample are set in the “antibacterial activity test”.
  • the column shows the evaluation results of antibacterial activity.
  • Examples other than the examples that is, the case where the pH of the antibacterial activity test sample is outside the range of 7.6 to 9.5 and / or the light projection amount is 0 J / m 2 , that is, the case where no light irradiation was performed. It is a comparative example of the present invention. In the comparative examples, the evaluation results of the antibacterial activity test were all (-), and no antibacterial activity was observed.
  • Example 3 ⁇ Antimicrobial activity test against Pseudomonas aeruginosa> (1) Obtaining Pseudomonas aeruginosa Pseudomonas aeruginosa was purchased from a strain distribution agency.
  • Antibacterial activity test An antibacterial activity test was conducted in the same manner as in Example 2.
  • the column of “Photodynamic therapy composition” in Table 3 the methylene blue concentration [w / v%], sodium bicarbonate concentration [w / v%] and pH of the antibacterial activity test sample are set in the “antibacterial activity test”.
  • the column shows the evaluation results of antibacterial activity.
  • Examples other than the examples that is, the case where the pH of the antibacterial activity test sample is outside the range of 7.6 to 9.5 and / or the light projection amount is 0 J / m 2 , that is, the case where no light irradiation was performed. It is a comparative example of the present invention. In the comparative examples, the evaluation results of the antibacterial activity test were all (-), and no antibacterial activity was observed.
  • Example 4 ⁇ Antimicrobial activity test against MRSA> (1) Obtaining MRSA A methicillin resistant strain (MRSA, Methicillin Resistant Staphylococcus aureus) of Staphylococcus aureus was purchased from a strain distribution agency.
  • MRSA Methicillin Resistant Staphylococcus aureus
  • MRSA suspension MRSA was cultured, the obtained culture was suspended in sterile physiological saline, and the number of bacteria was adjusted to prepare a bacterial solution.
  • Sample Methylene blue solution 10.0 mL, sodium hydrogen carbonate aqueous solution 1.0 mL, and bacterial solution 2.0 mL were mixed, and methylene blue shown in the column of “Composition for photodynamic therapy” in Table 4 Samples for antibacterial activity testing of concentration, sodium bicarbonate concentration, and pH were prepared. In addition, a blank sample was prepared by mixing 11.0 mL of physiological saline and 2.0 mL of bacterial solution.
  • Antibacterial activity test An antibacterial activity test was conducted in the same manner as in Example 2. In the column of “Composition for photodynamic therapy” in Table 4, the methylene blue concentration [w / v%], sodium bicarbonate concentration [w / v%] and pH of the antibacterial activity test sample are listed in the “antibacterial activity test”. The column shows the evaluation results of antibacterial activity.
  • Examples other than the examples that is, the case where the pH of the antibacterial activity test sample is outside the range of 7.6 to 9.5 and / or the light projection amount is 0 J / m 2 , that is, the case where no light irradiation was performed. It is a comparative example of the present invention. In the comparative examples, the evaluation results of the antibacterial activity test were all (-), and no antibacterial activity was observed.
  • Example 5 ⁇ Antimicrobial activity test against E. coli> (1) Obtaining Escherichia coli Escherichia coli was purchased from a strain distribution agency.
  • Antibacterial activity test An antibacterial activity test was conducted in the same manner as in Example 2. In the column of “Composition for photodynamic therapy” in Table 4, the methylene blue concentration [w / v%], sodium bicarbonate concentration [w / v%] and pH of the antibacterial activity test sample are listed in the “antibacterial activity test”. The column shows the evaluation results of antibacterial activity.
  • Examples other than the examples that is, the case where the pH of the antibacterial activity test sample is outside the range of 7.6 to 9.5 and / or the light projection amount is 0 J / m 2 , that is, the case where no light irradiation was performed. It is a comparative example of the present invention. In the comparative examples, the evaluation results of the antibacterial activity test were all (-), and no antibacterial activity was observed.

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