JP6412142B2 - Composition for photodynamic therapy, sterilization method, sterilization system and method of operating sterilization system - Google Patents

Description

  The present invention relates to a composition for photodynamic therapy, a sterilization method, a sterilization system or a method for operating a sterilization system.

  In photodynamic therapy for mucocutaneous infections, photosensitizers (photosensitive substances) are incorporated into pathogenic microorganisms present in lesions of mucocutaneous infections, and light with a wavelength corresponding to the photosensitizer is irradiated. In this method, active oxygen is generated from a photosensitizer and pathogenic microorganisms are sterilized to treat mucocutaneous infection.

  Photodynamic therapy is a promising alternative because there is no problem of increased resistance of pathogenic bacteria to antibiotics used in therapies that use antibiotics, such as tetracycline and β-lactam antibiotics. (Non-Patent Document 1).

  On the other hand, as a problem of photosensitizers used for photodynamic therapy, neutral or anionic photosensitizers that are currently widely used can provide sufficient antibacterial activity against gram-positive bacteria, but gram-negative bacteria. There is a problem that sufficient antibacterial power is not obtained. This is because Gram-positive bacteria and Gram-negative bacteria have different cell wall and cell membrane structures, and Gram-negative bacteria are negatively charged on the surface, so existing photosensitizers are difficult to be incorporated into Gram-negative bacteria. It is thought to be because.

  Cationic chlorin derivatives have been reported as photosensitizers effective against both gram-negative and gram-positive bacteria (Patent Document 1). However, the use of cationic chlorin derivatives is limited because the safety to the human body is unknown.

  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 2 discloses the use of methylene blue as an antibacterial agent in the dental field by utilizing cell death induced by singlet oxygen generated by light absorption. The overall mechanism of methylene blue cell killing is not clear, but the rigid and flat molecular structure intercalates into the DNA double helix structure and directly damages the DNA. It is described in Non-Patent Document 2 and Non-Patent Document 3.

  However, Patent Document 2 also suggests that the antibacterial activity of methylene blue is insufficient. A method by derivative synthesis has been studied for the purpose of enhancing the antibacterial activity of methylene blue (Patent Document 3). For example, Non-Patent Document 4 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). Yes. However, derivatization of the safe methylene blue used in the medical field does not ensure the safety to the living body, and clinical trials that require cost and time are required.

JP 2012-092024 A Japanese Patent No. 4564596 JP-T-2007-512297

Raab O. et al., Infusion Z. Biol., 39: 524 (1990) Wainwright M. et al., Inj. J. Antimicrob. Agents, 16 (4): 381 (2000) Rolim J.P. et al., J. Photochem. Photobaiol. B, 106: 40 (2012) Wainwright M. et al., J. Antimicrob. Chemotherapy, 44: 823 (1999) Strugatsky D. et al., Nature. Jan 10; 493 (7431): 255 (2013)

  However, other studies for enhancing the antibacterial activity of methylene blue, in particular, studies for enhancing the photosensitization effect by combining the functional additive disclosed in the present invention have not been conducted. In particular, there has been no report on its application to the eradication of Helicobacter pylori.

  Accordingly, the present invention provides a photodynamic therapy having high safety and a better bactericidal effect for treating H. pylori infection and other mucocutaneous infections by photodynamic therapy using methylene blue as a photosensitizer. It is an object of the present invention to provide a composition for sterilization, a method for sterilizing pathogenic microorganisms of Helicobacter pylori and other mucocutaneous infections, or a sterilization system for lesions caused by Helicobacter pylori infection or mucocutaneous infection and an operation method of the sterilization system .

  As a result of intensive studies to solve the above problems, the present inventors can accept at least one pharmaceutically acceptable selected from the group consisting of methylene blue, osmolyte, a reducing agent, urea, and a proton donor. H. pylori infection by combining with an additive, and mucocutaneous infection by combining methylene blue with at least one pharmaceutically acceptable additive selected from the group consisting of osmolyte and a reducing agent It was learned that the disease can be treated by photodynamic therapy with an effect superior to that of methylene blue alone and with safety equivalent to that of methylene blue alone.

That is, the present inventors have found that the above problem can be solved by the following configuration.
(1) A composition for photodynamic therapy for use in photodynamic therapy for treating H. pylori infection by contacting H. pylori present at the lesion site of H. pylori infection and irradiating H. pylori with light. A photodynamic therapy composition comprising methylene blue and at least one pharmaceutically acceptable additive selected from the group consisting of osmolite, a reducing agent, urea and a proton donor.
(2) The composition for photodynamic therapy according to (1) above, wherein the osmolyte is mannitol, the reducing agent is ascorbic acid, and the proton donor is histidine.
(3) The composition for photodynamic therapy according to (1) or (2) above, wherein the light is white light, LED light having a wavelength of 660 ± 10 nm, or laser light.
(4) The composition for photodynamic therapy according to any one of (1) to (3) above, wherein the light projection amount of light is 1 to 200 J / cm ² .
(5) A composition for photodynamic therapy for use in photodynamic therapy for treating skin mucosal infection by contacting with pathogenic microorganisms present at the lesion site of skin mucosal infection and irradiating the pathogenic microorganisms with light. A photodynamic therapy composition comprising methylene blue and at least one pharmaceutically acceptable additive selected from the group consisting of osmolite and a reducing agent.
(6) The composition for photodynamic therapy according to (5) above, wherein the osmolyte is mannitol and the reducing agent is ascorbic acid.
(7) The composition for photodynamic therapy according to (5) or (6) above, wherein the light is white light, LED light having a wavelength of 660 ± 10 nm or laser light.
(8) The composition for photodynamic therapy according to any one of (5) to (7) above, wherein the light projection amount of light is 1 to 200 J / cm ² .
(9) A step of bringing the composition for photodynamic therapy according to any one of (1) to (4) above into contact with Helicobacter pylori, and white light or LED light or laser light having a wavelength of 660 ± 10 nm to Helicobacter pylori. A method for sterilizing Helicobacter pylori,
(10) The method for sterilizing Helicobacter pylori as described in (9) above, wherein the light projection amount of white light, LED light, or laser light is 1 to 200 J / cm ² .
(11) The step of bringing the composition for photodynamic therapy according to any one of (5) to (8) above into contact with a pathogenic microorganism of a mucocutaneous infection, and causing the pathogenic microorganism to have white light or a wavelength of 660 ± 10 nm. A method for sterilizing pathogenic microorganisms of skin mucosal infections, comprising a step of irradiating LED light or laser light.
(12) The method for sterilizing pathogenic microorganisms of dermal mucosal infection according to (11) above, wherein the amount of light projection of white light, LED light or laser light is 1 to 200 J / cm ² .
(13) Imaging means, light irradiation means, composition ejecting means, imaging direction control 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, and composition An ejection direction control unit that controls the ejection direction of the ejection unit, an imaging unit, a light irradiation unit, a composition ejection unit, an imaging direction control unit, an irradiation direction control unit, and a calculation / control unit that controls the ejection direction control unit. A sterilization system for lesions caused by Helicobacter pylori infection or mucocutaneous infection,
(a) The imaging direction control means and the irradiation direction control means operate based on the control signal from the calculation / control unit so that the light irradiation means illuminates the observation area of the imaging means,
(b) Based on the control signal from the calculation / control unit, the imaging means images the skin / mucous membrane 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, and Identify and locate the lesion,
(d) The injection direction control means operates to match the injection direction of the composition injection means with the lesion based on the control signal from the calculation / control section,
(e) A composition injection means injects the composition for photodynamic therapy as described in any one of (1)-(8) based on the control signal from a calculation and control part,
(f) The irradiation direction control means operates to match the irradiation direction of the light irradiation means with the lesioned part based on the 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 or mucocutaneous infection.
(14) Imaging means, light irradiation means, composition ejecting means, imaging direction control 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, and composition An ejection direction control unit that controls the ejection direction of the ejection unit, an imaging unit, a light irradiation unit, a composition ejection unit, an imaging direction control unit, an irradiation direction control unit, and a calculation / control unit that controls the ejection direction control unit. A method of operating a sterilization system for lesions caused by Helicobacter pylori infection or mucocutaneous infection,
(a) a step of operating 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 in which the imaging means images the skin / mucous membrane based on a 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, and Identifying and identifying the location of the lesion,
(d) a step of operating the injection direction control means 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) a step of injecting the composition for photodynamic therapy according to any one of (1) to (8), based on a control signal from the calculation / control unit,
(f) a step of operating the irradiation direction control means based on a control signal from the calculation / control section so as to match the irradiation direction of the light irradiation means with the lesioned part, and
(g) 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, due to Helicobacter pylori infection or skin mucosal infection. The method of operating the lesion sterilization system.

  According to the present invention, using methylene blue as a photosensitizer, photodynamic therapy having high safety and better bactericidal effect for treating H. pylori infection and other skin mucosal infections by photodynamic therapy Composition, a method for sterilizing pathogenic microorganisms of Helicobacter pylori and other mucocutaneous infections, or a system for sterilizing lesions caused by Helicobacter pylori infection or skin mucosal infection, and a method for operating the sterilization system.

It is a key map showing a sterilization system. It is a perspective view which shows one specific example of a sterilization system. It is a front view which shows the front-end | tip cap of an endoscope. It is a front view which shows another aspect of the front-end | tip cap of an endoscope. It is sectional drawing which shows the flexible tube part of an endoscope. It is sectional drawing which shows another aspect of the flexible tube part of an endoscope.

  In this specification, the composition for photodynamic therapy for using in the photodynamic therapy which contacts the Helicobacter pylori which exists in the lesion site of a Helicobacter pylori infection, and irradiates light to Helicobacter pylori, and treats the Helicobacter pylori infection. Mucosal infections by contacting the pathogenic microorganisms with light and irradiating the pathogenic microorganisms with a photodynamic therapy composition for treating H. pylori infection and pathogenic microorganisms present at the lesion site of cutaneous mucosal infections Photodynamic therapy composition for use in photodynamic therapy to treat "photodynamic therapy composition for treating mucocutaneous infection" and photodynamic therapy for treating H. pylori infection The composition and the composition for photodynamic therapy for treating mucocutaneous infection are collectively referred to as “the composition for photodynamic therapy of the present invention”, a method for killing Helicobacter pylori and the pathogenesis of skin mucosal infection. They are collectively referred to as sterilization method of organisms may be referred to as "sterilization method of the present invention".

  Below, the suitable aspect of the composition for photodynamic therapy and the disinfection method of this invention is demonstrated in detail.

[Composition for photodynamic therapy]
The composition for photodynamic therapy of the present invention is used in photodynamic therapy for treating H. pylori infection by contacting H. pylori present on the lesion site of H. pylori infection and irradiating H. pylori with light. A photodynamic therapy composition comprising: methylene blue; and at least one pharmaceutically acceptable additive selected from the group consisting of osmolite, a reducing agent, urea, and a proton donor. Composition for photodynamic therapy for treating skin mucosal infection by contacting with pathogenic microorganisms present at lesion site of skin mucosal infection and irradiating light to pathogenic microorganisms A methylene blue and at least one pharmaceutically acceptable additive selected from the group consisting of osmolyte and a reducing agent It is a line photodynamic therapy composition.

<H. Pylori infection, mucocutaneous infection>
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. A mucocutaneous infection is an infection of the skin or mucous membrane caused by pathogenic microorganisms.
The skin is not particularly limited. The mucosa is not particularly limited, and includes oral mucosa, esophageal mucosa, gastric mucosa, intestinal mucosa, nostril, lips, ears, genital organs, anus and the like.
The pathogenic microorganisms for dermal mucosal infections include Escherichia coli, Pseudomonas aeruginosa, Helicobacter pylori, Staphylococcus aureus, Streptococcus sp., Mycobacterium Pathogenic bacteria such as Mycobacterium sp. And Treponema sp. Parasites such as Candida sp., Cryptococcus sp. And Malassezia sp. Examples include insects, amoeba such as Acanthamoeba, and viruses having an envelope such as herpes simplex virus.

<Methylene blue>
Methylene blue [3,7-bis (dimethylamino) phenothiazinium chloride] is not particularly limited. For example, it may be an anhydride or a hydrate. Examples of the hydrate include, but are not limited to, dihydrate, trihydrate, tetrahydrate and the like. In addition, methylene blue may be sold as a pharmaceutical or may be sold as a reagent. The reagent is preferably of a high purity, for example, those specified in JIS K 8897: 2012. Moreover, what melt | dissolved methylene blue in solvent (ethanol etc.) and made it the solution of a density | concentration of about 5.0 w / v% is also preferable.
“W / v%” means “weight / volume%” and represents the mass (g) of a drug or the like (solute) dissolved in 100 mL of the solution.

  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.

  In the photodynamic therapy composition of the present invention, methylene blue can be used at any concentration. The concentration at the time of contacting methylene blue with H. pylori or other pathogenic microorganisms of skin mucosal infection (concentration at the time of use) is not particularly limited, but is preferably 0.001 w / v% or more, more preferably 0.005 w / v%. More preferably, it is 0.01 w / v% or more, more preferably 0.03 w / v% or more, and still more preferably 0.05 w / v% or more. The upper limit of the concentration of methylene blue at the time of use is not particularly limited, but it is difficult to make a significant difference in the bactericidal effect in a high concentration range, so that it is preferably 5.0 w / v% or less, more preferably 3.0 w / v%. Hereinafter, it is more preferably 1.0 w / v% or less, and still more preferably 0.5 w / v% or less. More specifically, the in-use concentration range of methylene blue is preferably 0.001 w / v% to 5.0 w / v%, more preferably 0.005 w / v% to 5.0 w / v%, still more preferably 0. 0.01 w / v% to 5.0 w / v%, more preferably 0.03 w / v% to 5.0 w / v%, and even more preferably 0.05 w / v% to 5.0 w / v%. The upper limit of the in-use concentration range of methylene blue may be 1.0 w / v%, 0.5 w / v%, or 0.1 w / v% instead of 5.0 w / v%.

<Pharmaceutically acceptable additives>
The photodynamic therapy composition for treating H. pylori infection comprises at least one pharmaceutically acceptable additive selected from the group consisting of osmolytes, reducing agents, urea and proton donors. Any one of osmolyte, reducing agent, urea and proton donor may be used, or two or more of them may be used.
The composition for photodynamic therapy for treating mucocutaneous infection also contains at least one pharmaceutically acceptable additive selected from the group consisting of osmolite and a reducing agent. Any one or two of osmolite and reducing agent may be used.

《Osmolite》
Osmolyte is an osmotic pressure regulator for changing the osmotic pressure around the pathogenic microorganisms of H. pylori or mucocutaneous disease. It promotes the uptake of methylene blue into the inside of H. pylori or pathogenic microorganisms by changing the surrounding osmotic pressure.

  The osmolite is not particularly limited as long as it can change the osmotic pressure around the pathogenic microorganism of H. pylori or skin mucosa disease. Moreover, osmolite can be used individually by 1 type or in combination of 2 or more types.

Specific examples of the osmolite include inorganic ions such as potassium ion (K ⁺ ) and chloride ion (Cl ⁻ ), monosaccharides such as glycerol, mannitol, trehalose, glucose, sucrose, sorbitol, and inositol. Amino acids such as disaccharides and polyhydric alcohols, alanine, β-alanine, glycine, glutamic acid, proline, GABA (γ-aminobutyric acid), ectoine; aminosulfonic acids such as taurine; trimethylamine-N-oxide (TMAO), Examples thereof include methylammonium and sulfonium such as glycine betaine (such as trimethylglycine), proline betaine, glycerophosphocholine (GPC), and dimethylsulfoniopropinate (DMSP). Among these, monosaccharides / disaccharides / polyhydric alcohols such as glycerol, mannitol, trehalose, glucose, sucrose, sorbitol, and inositol are preferable, and they have abundant experience in clinical practice. Mannitol is most preferred because of its safety.

In the composition for photodynamic therapy of the present invention, osmolyte can be used in any concentration.
When mannitol is used as the osmolite, the concentration of mannitol when used is not particularly limited, but is preferably 0.01 w / v% or more, more preferably 0.03 w / v% or more, and even more preferably 0.05 w / v. % Or more, more preferably 0.10 w / v% or more. The upper limit of the concentration of mannitol when used is not particularly limited, but since the bactericidal effect reaches a plateau, it is preferably 10 w / v% or less, more preferably 5.0 w / v% or less, and even more preferably 3.0 w / v. % Or less. More specifically, the concentration range of mannitol when used is preferably 0.01 w / v% to 10 w / v%, more preferably 0.03 w / v% to 10 w / v%, and still more preferably 0.05 w / v. % To 10 w / v%, more preferably 0.10 to 10 w / v%. The upper limit of the concentration range during use may be 5.0 w / v%, 3.0 w / v%, or 1.0 w / v% instead of 10 w / v%.

《Reducing agent》
The reducing agent reduces methylene blue to convert it into reduced leuco methylene blue, and enhances the bactericidal effect by inhibiting the ATP synthesis pathway of H. pylori or pathogenic microorganisms with its reducing power.

  It has been found that methylene blue is easily reduced to colorless leucomethylene blue by being reduced by intracellular NAD. Leucomethylene blue has a strong reducing power and can be expected to increase the killing power by acting on the ATP production cycle of H. pylori or pathogenic microorganisms.

  The reducing agent is not particularly limited as long as it can reduce methylene blue to leucomethylene blue. Moreover, a reducing agent can be used individually by 1 type or in combination of 2 or more types.

  As a reducing agent, methylene blue can be rapidly converted to leucomethylene blue, so that low molecular weight reductions such as glutathione, N-acetylcysteine, ascorbic acid, α-tocopherol, butylhydroxyanisole, catechin, quercetin, uric acid, bilirubin, glucose, flavonoids, etc. Ascorbic acid is most preferred because it is preferable, has a proven track record in clinical practice, and is biologically safe when administered to the body. These compounds may be metal salts such as sodium salts or hydrates.

In the composition for photodynamic therapy of the present invention, the reducing agent can be used at any concentration.
When sodium ascorbate is used as the reducing agent, the concentration of sodium ascorbate when used is not particularly limited, but is preferably 0.01 w / v% or more, more preferably 0.04 w / v% or more, and still more preferably 0.8. 07 w / v% or more, more preferably 0.10 w / v% or more. The upper limit of the concentration of sodium ascorbate at the time of use is not particularly limited, but since the bactericidal effect reaches a plateau, it is preferably 10 w / v% or less, more preferably 5.0 w / v% or less, and even more preferably 2.0 w. / V% or less, more preferably 1.0 w / v% or less, and even more preferably 0.50 w / v% or less. More specifically, the concentration range of sodium ascorbate in use is preferably 0.01 w / v% to 10 w / v%, more preferably 0.04 w / v% to 10 w / v%, and still more preferably 0.07 w. / V% to 10 w / v%, more preferably 0.10 w / v% to 10 w / v%. The upper limit of the concentration range of sodium ascorbate when used may be 5.0 w / v%, 3.0 w / v%, 1.0 w / v%, or 0.50 w / v% instead of 10 w / v% Good.

"urea"
Urea is a substrate for urease and enhances the bactericidal effect of Helicobacter pylori by changing the inside or the periphery of Helicobacter pylori to basic by ammonia produced by hydrolysis by urease of H. pylori.

  Helicobacter pylori expresses urease with two optimum pH in neutral and acidic regions, hydrolyzes urea in the stomach to produce ammonia, and locally neutralizes gastric acid, Enables colonization and growth in the stomach. However, when urea is excessively supplied from outside the cells, it becomes more basic than the optimum pH 6.1 for survival of H. pylori, and it can be expected that the sterilization efficiency is supplementarily increased.

  In the photodynamic therapy composition for treating H. pylori infection of the present invention, urea can be used at any concentration. The concentration of urea in use is not particularly limited, but is preferably 0.01 w / v% or more, more preferably 0.05 w / v% or more, still more preferably 0.10 w / v% or more, and still more preferably 0.15 w. / V% or more, more preferably 0.20 w / v% or more. The upper limit of the use concentration of urea is not particularly limited, but since the bactericidal effect reaches a plateau, it is preferably 10 w / v% or less, more preferably 5.0 w / v% or less, and even more preferably 2.0 w / v. % Or less, more preferably 1.0 w / v% or less, and even more preferably 0.50 w / v% or less. More specifically, the concentration range of urea in use is preferably 0.01 w / v% to 10 w / v%, more preferably 0.05 w / v% to 10 w / v%, and still more preferably 0.10 to 10 w. / V%, more preferably 0.15 to 10 w / v%, even more preferably 0.20 to 10 w / v%. The upper limit of the concentration range of urea when used may be 5.0 w / v%, 22.0 w / v%, 1.0 w / v%, or 0.50 w / v% instead of 10 w / v%.

<Proton donor>
The proton donor changes the cell membrane and enzyme activity of H. pylori.
The cell membrane of H. pylori has a proton-sensitive urea channel that closes at a neutral pH and opens at an acidic pH, and maintains the spatial periplasm between the cell membrane (inner membrane) and the outer membrane at pH 6.1, which is the optimum pH.
The periplasm contains metabolic enzymes necessary for life support of Helicobacter pylori. In an acidic environment, the channel opens, and protons and urea flow into it, making it easier to contact urease. If there is an additive that releases protons, protons and urea flow in excessively from the open channel, but Helicobacter pylori increases ammonia production by urease and changes the pH to the basic side to maintain the optimum pH. To do. Even if the channel is closed, if the excessively flowing urea is decomposed and the pH rises, an environment inappropriate for survival is formed in H. pylori cytoplasm and periplasm (Non-patent Document 5). In addition, when mannitol, which is a polyhydric alcohol having an effect of increasing the acid dissociation degree (pKa) of a weak acid, coexists, it can be expected that the function of the proton donor is further enhanced.

The proton donor is not particularly limited as long as it can release hydrogen ions (H ⁺ ) and open the proton-sensitive urea channel of the Helicobacter pylori cell membrane. Moreover, a proton donor can be used individually by 1 type or in combination of 2 or more types.

  As a proton donor, lysine, arginine, histidine, and tryptophan are preferable because they are proton-releasing basic amino acids, and histidine is the most preferable because it has an imidazole group and is thought to change cell membranes and enzyme activities. preferable. As these basic amino acids, salts such as hydrochloride, hydrates, and enantiomers may be used.

In the composition for photodynamic therapy for treating H. pylori infection of the present invention, the proton donor can be used in any concentration.
When histidine is used as a proton donor, the concentration of histidine when used is not particularly limited, but is preferably 0.50 mM or more, more preferably 0.75 mM or more, still more preferably 1.0 mM or more, and still more preferably 2. It is 0 mM or more, more preferably 3.5 mM or more. The upper limit of the concentration of histidine when used is not particularly limited, but is preferably 200 mM or less, more preferably 100 mM or less, still more preferably 75 mM or less, and even more preferably 50 mM or less because the bactericidal effect reaches a plateau. More particularly, the concentration range of histidine in use is preferably 0.50 mM to 200 mM, more preferably 0.75 mM to 200 mM, even more preferably 1.0 to 200 mM, even more preferably 2.0 to 200 mM, even more. Preferably it is 3.5-200 mM. The upper limit of the concentration range of histidine in use may be 100 mM or less, 75 mM or less, or 50 mM or less, instead of 200 mM.
“MM” represents 10 ⁻³ M (10 ⁻³ mol / L).

  The photodynamic therapy composition of the present invention may contain one or more pharmaceutically acceptable carriers, diluents or excipients. The photodynamic therapy composition of the present invention may further comprise liposomes, nanoparticles, colloidal suspensions, micelles, microemulsions, vesicles and nanospheres. The photodynamic therapy composition of the present invention may also contain additional ingredients such as conventional delivery vehicles and excipients, which may be a solvent such as an alcohol (eg ethanol, polyethylene glycol, glycerol or n-butanol). ), Dimethyl sulfoxide, water, saline, solubilizer, pH adjuster, gelling agent, thickener, buffer and combinations thereof.

  Typically, it can be prepared by mixing the photodynamic therapy composition of the present invention and one or more pharmaceutically acceptable carriers at a suitable temperature and a suitable pH. Suitable pH typically includes 15-65 ° C. Suitable pH typically includes pH 3-9, preferably physiologically relevant pH, such as pH 6.5-7.5.

  The photodynamic therapy composition provided by the present invention may be a dry composition that can be reconstituted prior to use, or may be in the form of a prefill that has been pre-sterilized and sealed. Alternatively, methylene blue and an additive may be aseptically dissolved in pure water or physiological saline and aseptically filled into a syringe having a tube at the tip.

  The composition for photodynamic therapy of the present invention can also be used as an antibacterial agent, antifungal agent and antiviral agent.

The composition for photodynamic therapy of the present invention can be used not only for humans but also for animals other than humans. Examples of non-human animals include, without limitation, non-human mammals including monkeys, cats, pigs, dogs and the like. In addition to mammals, examples of animals other than humans include, but are not limited to, vertebrates other than mammals such as birds, reptiles, amphibians, and fish. Examples of animals other than humans include dogs, cats, foxes, horses, pigs, sheep, goats, donkeys, camels, etc. Examples of such pets include, but are not limited to.
Furthermore, the composition for photodynamic therapy of the present invention can be used not only in vivo but also in vitro.

  Examples of use of the photodynamic therapy compositions of the present invention include use as antimicrobial and antifungal treatments for skin and wound infections such as burns; use for parasitic infections, stomach infections, malaria, leprosy; bacteria And use for fungal spore inactivation; use for the treatment of prion and viral infections such as HIV; ear, nose and throat infection, use for tuberculosis; sexually transmitted disease (STD), for herpes Use; eg for the treatment of Candida local infections of the hair, nails and epidermis, eg foot and body tinea and vulvar candidiasis; and infection preventives eg surgical wound disinfection, skin disinfection, stem cell disinfection, transplantation Use as a one-to-host rejection disease; skin diseases such as psoriasis, acne, vitiligo and eczema and other skin conditions such as hirsutism and sunburn damage, etc. Use for benign conditions such as endometriosis and menorrhagia; oral bacteriosis such as gingival abscess, periodontal disease, gingivitis, and use for removal, inactivation or death of plaque biofilm and Used for Helicobacter pylori eradication.

  The composition for photodynamic therapy can be administered intravenously, orally, transdermally, transmucosally, intramuscularly or the like, but preferably administered locally. In addition, administration by direct spraying through the endoscope to the lesion site of the upper digestive tract or the lower digestive tract, specifically, methylene blue and additives are dissolved in pure water or physiological saline, and a tube is provided at the tip. It is preferable to fill the syringe, insert a tube into the forceps opening of the endoscope, and push the syringe to spray the drug on the stomach wall or the like.

  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.

[Sterilization method]
The sterilization method using the composition for photodynamic therapy of the present invention comprises a step of bringing the composition for photodynamic therapy of the present invention into contact with H. pylori or pathogenic microorganisms of skin mucosal infection, and irradiating H. pylori or pathogenic microorganisms with light. And a step of performing.

  The method for bringing the composition for photodynamic therapy of the present invention into contact with Helicobacter pylori or a pathogenic microorganism of mucocutaneous infection is not particularly limited. For example, the composition for photodynamic therapy of the present invention can be used according to the above dosage form and administration method. Examples thereof include a method of administering to a subject and a method of contacting the photodynamic therapy composition of the present invention in a solid or solution state in vitro.

The sterilization method using the composition for photodynamic therapy of the present invention can be applied to humans as well as animals other than humans. Examples of non-human animals include, without limitation, non-human mammals including monkeys, cats, pigs, dogs and the like. In addition to mammals, examples of animals other than humans include, but are not limited to, vertebrates other than mammals such as birds, reptiles, amphibians, and fish. Examples of animals other than humans include dogs, cats, foxes, horses, pigs, sheep, goats, donkeys, camels, etc. Examples of such pets include, but are not limited to.
Furthermore, the sterilization method using the composition for photodynamic therapy of the present invention can be used in vivo or in vitro.

  Activation of the photodynamic therapy composition of the present invention by light is by light containing a suitable wavelength, usually white light, or red light in the range of 600 nm to 800 nm. The wavelength of the light is preferably 630 nm to 700 nm, particularly preferably 660 ± 10 nm.

  The light source is not particularly limited as long as it can emit light having the above wavelength, and may be a coherent light source or an incoherent light source. Examples of the coherent light source include a laser and a laser diode, and an AlGaInP (aluminum gallium indium phosphide) quantum well structure laser diode or an aluminum gallium arsenide laser having a wavelength of 660 nm is particularly preferable. Examples of the incoherent light source include a light emitting diode (LED), an incandescent lamp, a fluorescent lamp, and the like, and a red LED that emits red light having a wavelength of 660 nm is particularly preferable.

The white light may also 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. Here, the phosphor absorbs a part of blue laser light and emits green to yellow excitation light (for example, YAG (yttrium, aluminum, garnet) phosphor, BAM (barium / aluminum)). It is preferable to use a material including an oxide (phosphor such as BaMgAl ₁₀ O ₁₇ : Eu ²⁺ ).

The amount of light to be projected (projection light amount, energy density) is preferably 1 J / cm ^{2 to} 200 J / cm ² , more preferably 5 J / cm ^{2 to} 100 J / cm ² , and even more preferably 10 to 30 J / cm ² . Within this range, a safer and higher sterilizing effect can be expected.

[Sterilization system and its operating method]
In addition, the present invention uses a composition for photodynamic therapy of the present invention to sterilize a lesion due to Helicobacter pylori infection or mucocutaneous infection (hereinafter sometimes simply referred to as “sterilization system of the present invention”). And an operating method thereof (hereinafter, simply referred to as “an operating method of the sterilization system of the present invention”).

  The outline of the sterilization system of the present invention and the operation method thereof will be described below with reference to the drawings as appropriate.

  As shown in FIG. 1, the sterilization system 100 includes a calculation / control unit 101, an imaging unit 102, an imaging direction control unit 103, a light irradiation unit 102, an irradiation direction control unit 103, and a composition injection unit 104. The injection direction control means 105 and the transmission paths 108 to 113 are provided.

  The imaging unit 102 includes an imaging optical system 102a including an imaging device (not shown) that images the observation region, a signal processing unit that performs analog / digital conversion processing of an image signal from the imaging 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 of a subject to be imaged and outputs an image signal. The imaging device is preferably a CCD (Charge Coupled Device) image sensor or a CMOS (Complementary Metal-Oxide Semiconductor) image sensor.

  The imaging direction control unit 103 includes a drive mechanism that changes the imaging direction of the imaging unit 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 means 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. For example, 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. Among these, white light is preferable because a natural color tone of the observation region can be obtained. In addition, for example, in order to distinguish between a normal region and an abnormal region of the observed region based on a color difference from the normal region due to an inflammatory reaction or the like occurring in the abnormal region, light that emphasizes the color difference is used. It is preferable. Furthermore, as 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, and the wavelength is 660 ±. It is more preferable to irradiate 10 nm LED light or laser light.

  The irradiation direction control unit 105 includes a drive mechanism for changing the irradiation direction of the light irradiation unit 106 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 110.

  The composition injection means 106 has an injection part 106 a having an opening for injecting the composition for photodynamic therapy of the present invention (sometimes simply referred to as “the composition of the present invention”), and the composition of the present invention is stored therein. A liquid supply tank (not shown), a liquid supply pump (not shown) for injecting the composition of the present invention, and an interface with the calculation / control unit 101. The composition injection unit 106 is controlled based on a control signal from the calculation 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.

  Further, the opening of the injection unit 106a may be a simple hole or a nozzle capable of spraying the composition 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.

  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.

  Next, an operation method of the sterilization system 100 when sterilizing a lesion due to Helicobacter pylori infection or mucocutaneous infection will be described.

(Identification of the location of the lesion due to Helicobacter pylori infection or mucocutaneous infection)
(a) 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.
(b) The imaging unit 102 images the skin / 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.
(c) 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.

(Injection of composition for photodynamic therapy)
(d) The injection direction control means 107 is operated based on a control signal from the calculation / control section 101 so that the injection direction of the composition injection means 106 matches the lesioned portion 202.
(e) 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.

(Light irradiation to the composition for photodynamic therapy)
(f) 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.
(g) 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.

In order to reduce the risk of light irradiation other than the lesioned part to which the composition for photodynamic therapy is attached, the light irradiation to the composition for photodynamic therapy may be performed as follows.
(f1) 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.
(f2) The imaging unit 102 images the skin / mucous membrane 200 based on a control signal from the calculation / control unit 101 and transmits a video signal to the calculation / control unit 101.
(f3) 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.

(Sterilization system using electronic endoscope)
The case where an electronic endoscope system is utilized is concretely demonstrated about the sterilization system of this invention, and its operating method.

  A 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.

  Generally speaking, the difference from conventional electron microscope systems (for example, Japanese Patent No. 5485081, Japanese Patent No. 5503467, etc.) is that the arithmetic and control unit 12 shown in FIG. The liquid delivery device 15 can deliver the composition for photodynamic therapy of the present invention to the endoscope 11, and has an image processing unit that identifies the position of the abnormal site. 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 (see FIG. 3A, see FIG. 3B) to the point where mucosal lesions or areas where the composition for photodynamic therapy of the present invention is attached can be irradiated with white light or LED light or laser light having a wavelength of 660 ± 10 nm. Ah .

  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. Further, the tip cap 20 has a liquid such as a composition for photodynamic therapy of the present invention, washing water, a chemical solution, or the like toward a portion to be observed in the subject (hereinafter sometimes referred to as “observed site”). Are provided with a water jet outlet (hereinafter sometimes referred to as “WJ outlet”) 24 and an injection nozzle 25 for injecting air or cleaning water toward the observation window 21. 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 site in the subject with 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 (forceps) having an injection needle, a high-frequency knife or the like arranged at the tip are inserted into the forceps inlet 26.

2 includes an up / down bending angle knob 28 for bending the bending portion 16b in the up / down direction, a left / right bending angle knob 29 for bending the bending portion 16b in the left / right direction, and air in the observation window 21. And an air / water button 30 for feeding cleaning water may be provided.
When 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. When 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.

Normally, when the sterilization system 10 is operated, it is not necessary to operate the up / down bending angle knob 28, the left / right bending angle knob 29, and the air / water supply button 30.
In order to bend the bending portion 16b, 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.
In order to supply air, 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. In order to perform water supply, 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.

In addition, 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. 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 device 12 shown in FIG. 2 performs various types of image processing on the image pickup signal input from the image pickup device via the universal code 18 and the connector 32 to generate 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 disposed on the front surface of the apparatus main body 36 for sending out 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.

  As shown in FIGS. 4A and 4B, inside the flexible tube portion 16c, there are light guides 41a and 41b, forceps tubes 42, air / water supply tubes 43, multi-core cables 44, water jet tubes (hereinafter simply referred to as “ It may be called “WJ tube”.) 45 is arranged.

  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. ) And 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. And a second WJ path 47b in communication. The first WJ path is connected to a WJ soft tube (not shown).
In the above embodiment, the second WJ path is linearly formed on an orthogonal plane orthogonal to the photographing optical axis, but may be bent or curved as long as it is on the orthogonal plane. .

  The distal end portion 16a is made of a metal columnar distal end portion main body (not shown) and a metal distal end pipe (not shown) that covers the distal end 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 (not shown) including an imaging lens (not shown) and an imaging element (not shown) is disposed behind the observation window 21. 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 region 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.

Next, an operation method of the sterilization system 10 configured as described above will be described.
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.

  Light from the light source device 13 is irradiated to an observation site in the subject through light guides 41a and 41b, an illumination optical system (not shown), and 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 an imaging signal. This imaging 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.
In addition, the arithmetic / control device 12 can perform various image processing on the input imaging signal to generate an image in the subject, and display the image in the subject on the monitor 33.

  When observing the inside of the subject, the calculation / control apparatus 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.

  Instead of transmitting a control signal to the operation unit 17 to operate the bending unit up-down direction bending mechanism and the bending unit left-right bending mechanism, the calculation / control device 12 gives an instruction to the operator, and each angle of the operation unit 17 is set. The knobs 28 and 29 may be operated to bend the bending portion 16b in the vertical direction and the horizontal direction.

  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. The 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.

  Next, 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.

  Before the light irradiation, 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 observation site 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.
Next, 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. Irradiate toward the area where the object is attached. 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.

  The following examples further illustrate the present invention, but the present invention is not limited to the examples.

[PDT (Photodynamic Therapy) Antibacterial Test]
1. Materials (1) Helicobacter pylori JCM 12093 strain (2) Methylene blue (methylene blue stock solution, 5.0 w / v%, manufactured by Kishida Chemical Co., Ltd.)
(3) D-mannitol (Japanese Pharmacopoeia D-mannitol injection solution, 20 w / v%; manufactured by Nippon Pharmaceutical Co., Ltd.)
(4) Ascorbic acid (L (+)-sodium ascorbate, manufactured by Wako Pure Chemical Industries, Ltd., Wako special grade)
(5) Urea (Wako Pure Chemical Industries, Ltd., reagent special grade)
(6) D-histidine (D-histidine hydrochloride monohydrate, manufactured by Wako Pure Chemical Industries, Ltd., Wako Special Grade)
(7) L-histidine (L-histidine hydrochloride monohydrate, manufactured by Tokyo Chemical Industry Co., Ltd.)
(8) Sterile purified water (Japan Pharmacopoeia sterilized purified water)
(9) Saline (Japanese Pharmacopoeia, Saline)
(10) Ethanol (ethanol (99.5), manufactured by Wako Pure Chemical Industries, Ltd., reagent special grade)

2. Preparation of fungus solution and reagent (1) Preparation of H. pylori suspension (bacterial solution) JCM 12093 strain was purchased, and the bacterial species was identified and confirmed using the Apihelico culture identification kit (manufactured by Sysmex Biomelieu). A culture was used.
The cultured H. pylori was suspended in sterile physiological saline, and the number of bacteria was adjusted to 2.0 × 10 ⁸ cells / mL.

(2) Preparation of methylene blue (MB) solution 5 mL of physiological saline was taken and used as an MB solution having an MB concentration of 0.0 w / v%.
Take 10 μL, 30 μL, 50 μL, and 100 μL of 5 w / v% methylene blue stock solution, fill up to 5 mL with physiological saline, respectively, and prepare MB concentrations of 0.01 w / v%, 0.03 w / v%, 0.05 w / 5 mL of v% and 0.1 w / v% MB solutions were prepared.

(3) Preparation of D-mannitol aqueous solution A sterilized purified water was used to prepare a D-mannitol aqueous solution having a concentration of 0 w / v%.
Using D-mannitol and sterilized purified water, D-mannitol aqueous solutions having concentrations of 0.5 w / v%, 1.0 w / v%, and 2.0 w / v% were prepared.

(4) Preparation of Ascorbic Acid Aqueous Solution An ascorbic acid aqueous solution having a concentration of 0 w / v% was prepared using sterilized purified water.
An ascorbic acid aqueous solution having a concentration of 0.6 w / v% was prepared using ascorbic acid and sterilized purified water.

(5) Preparation of urea aqueous solution A urea aqueous solution having a concentration of 0 w / v% was prepared using sterilized purified water.
A urea aqueous solution having a concentration of 2.0 w / v% was prepared using urea and sterilized purified water.

(6) Preparation of aqueous solution of D-histidine An aqueous solution of D-histidine having a concentration of 0 M was prepared using sterilized purified water.
Using D-histidine and sterilized purified water, D-histidine aqueous solutions having concentrations of 0.01M, 0.03M, and 0.05M were prepared.

(7) Preparation of L-histidine aqueous solution An L-histidine aqueous solution having a concentration of 0 M was prepared using sterilized purified water.
An L-histidine aqueous solution having a concentration of 0.01 M was prepared using L-histidine and sterilized purified water.

3. Antibacterial activity test <Example 1> When osmolyte (D-mannitol) is added as an additive Bacterial fluid (20 μL), methylene blue solution with each concentration shown in Table 1 (100 μL), and D- with each concentration shown in Table 1 Prepare microbial / reagent mixture (130 μL) by mixing mannitol aqueous solution (10 μL), immediately add the whole amount (130 μL) to Helicobacter agar medium (Nissui Pharmaceutical Co., Ltd.) And left in the dark for 5 minutes.
After standing for 5 minutes, the cells were cultured in an incubator at 37 ° C. for 4 days with or without irradiation with LED light (wavelength 660 nm, projection amount 15 J / m ² ) for 4 minutes.
After culturing for 4 days, the number of surviving colonies of each medium (No. 1-40) was counted, compared with blank (No. 21), and antibacterial activity was evaluated according to the following criteria.

(Standard for antibacterial activity evaluation)
-: No effect The decrease rate of the number of surviving colonies is less than 20% compared to the blank. +: The effect is less than the blank. The decrease rate of the viable colony number is 20% or more and less than 40%. 2+: Effective The rate of decrease in the number of surviving colonies is 40% or more and less than 60% 3+: Effectiveness The rate of decrease in the number of surviving colonies is 60% or more and less than 80% 4+: Effective The number of surviving colonies compared to the blank Decrease rate is 80% or more. 5+: Effective and the number of surviving colonies is 0.

  In Table 1, No. Are numbered in ascending order from the left. For example, no. 1-5 is No. 1 from the left side. 1, no. 2, no. Numbered 3 ... The same applies to Tables 2 to 5.

<< Group without light irradiation (No. 21 to 40) >>
In the group without light irradiation (No. 21 to 40), the antibacterial activity evaluation was “−” regardless of the addition amount of methylene blue and the additive, and the antibacterial activity was not recognized.

<< Group with light irradiation (No. 1-20) >>
The group containing no methylene blue (No. 1, 6, 11, 16; group to which a methylene blue solution having a concentration of 0 w / v% was added) had an antibacterial activity evaluation of “−” and no antibacterial activity was observed.
The group containing methylene blue (No. 2 to 5, 7 to 10, 12 to 15, 17 to 20; a group to which a methylene blue solution having a concentration of 0.01 to 0.10 w / v% was added) was evaluated for antibacterial activity. 3+ "to" 5+ ", and antibacterial activity was observed.
In the group containing methylene blue, when the methylene blue concentration was the same, the D-mannitol concentration was compared with the group containing no D-mannitol (group to which a D-mannitol aqueous solution having a concentration of 0 w / v% was added; No. 2 to 5). The group containing mannitol (group to which a D-mannitol aqueous solution having a concentration of 0.5 to 2.0 w / v% was added; No. 7 to 10, 12 to 14, 17 to 20) has high antibacterial activity evaluation, and D- Enhancement of antibacterial activity by addition of mannitol was observed (No. 7, 12, 17, etc. with respect to No. 2).

<Example 2> When a reducing agent (sodium ascorbate) is added as an additive Bacterial fluid (20 μL), methylene blue solution (100 μL) with each concentration shown in Table 2, and aqueous sodium ascorbate solution with each concentration shown in Table 2 ( 10 μL) to prepare a bacteria / reagent mixed solution (130 μL), immediately add the entire amount (130 μL) to Helicobacter agar medium (manufactured by Nissui Pharmaceutical Co., Ltd.), Left in the dark for 5 minutes.
After standing for 5 minutes, the cells were cultured in an incubator at 37 ° C. for 4 days with or without irradiation with LED light (wavelength 660 nm, projection amount 15 J / m ² ) for 4 minutes.
After incubating for 4 days, the number of surviving colonies in each medium (No. 1-12) was counted, compared with the blank (No. 7), and antibacterial activity was evaluated according to the above “standard for antibacterial activity evaluation”.

<< Group without light irradiation (No. 7-12) >>
In the group without light irradiation (Nos. 7 to 12), the antibacterial activity evaluation was “−” regardless of the addition amount of methylene blue and the additive, and no antibacterial activity was observed.

<< Group with light irradiation (No. 1-6) >>
The groups not containing methylene blue (No. 1, 4; group to which a methylene blue solution having a concentration of 0 w / v% was added) had an antibacterial activity evaluation of “−”, and no antibacterial activity was observed.
The group containing methylene blue (No. 2, 3, 5, 6; group to which a methylene blue solution having a concentration of 0.05 to 0.10 w / v% was added) had an antibacterial activity evaluation of “4+” or “5+” Antibacterial activity was observed.
In the group containing methylene blue, when the methylene blue concentration was the same, ascorbic acid was compared with the group not containing sodium ascorbate (groups to which a sodium ascorbate aqueous solution having a concentration of 0 w / v% was added; No. 2, 3). The group containing sodium (group to which an aqueous sodium ascorbate solution having a concentration of 0.6 w / v% was added; No. 5 and 6) had high antibacterial activity evaluation, and the enhancement of antibacterial activity by addition of sodium ascorbate was recognized. (No. 5 for No. 2, etc.).

<Example 3> When urea is added as an additive Bacterial solution (20 μL), methylene blue solution (100 μL) of each concentration shown in Table 3 and urea aqueous solution (10 μL) of each concentration shown in Table 3 A reagent mixture (130 μL) was prepared, and immediately the entire amount (130 μL) was added to a Helicobacter agar medium (manufactured by Nissui Pharmaceutical Co., Ltd.), and evenly applied to the medium with a conage bar, and left in the dark for 5 minutes.
After standing for 5 minutes, the cells were cultured in an incubator at 37 ° C. for 4 days with or without irradiation with LED light (wavelength 660 nm, projection amount 15 J / m ² ) for 4 minutes.
After incubating for 4 days, the number of surviving colonies in each medium (No. 1 to 16) was counted, compared with the blank (No. 9), and antibacterial activity was evaluated according to the above “standard for antibacterial activity evaluation”.

<< Group without light irradiation (No. 9 to 16) >>
In the group without light irradiation (Nos. 9 to 16), the antibacterial activity evaluation was “−” regardless of the addition amount of methylene blue and the additive, and no antibacterial activity was observed.

<< Group with light irradiation (No. 1-8) >>
The groups not containing methylene blue (No. 1, 5; group to which a methylene blue solution having a concentration of 0 w / v% was added) had an antibacterial activity evaluation of “−” and no antibacterial activity was observed.
The group containing methylene blue (No. 2 to 4, 6 to 8; a group to which a methylene blue solution having a concentration of 0.01 to 0.10 w / v%) was added had an antibacterial activity evaluation of “3+” to “5+” Antibacterial activity was observed.
In the group containing methylene blue, when the methylene blue concentration is the same, the group containing urea compared to the group not containing urea (group to which a urea aqueous solution having a concentration of 0 w / v% was added; No. 2 to 4) ( The group to which a 2.0 w / v% aqueous urea solution was added; No. 6 to 8) had high antibacterial activity evaluation, and enhanced antibacterial activity by adding urea (No. 6 to No. 2, etc.) .

<Example 4> When a proton donor (D-histidine) is added as an additive Bacterial fluid (20 μL), methylene blue solutions (100 μL) having various concentrations shown in Table 4, and D-histidine aqueous solutions having various concentrations shown in Table 4 (10 μL) is mixed to prepare a bacteria / reagent mixed solution (130 μL), and immediately after adding the entire amount (130 μL) to Helicobacter agar medium (Nissui Pharmaceutical Co., Ltd.) Left in the dark for 5 minutes.
After standing for 5 minutes, the cells were cultured in an incubator at 37 ° C. for 4 days with or without irradiation with LED light (wavelength 660 nm, projection amount 15 J / m ² ) for 4 minutes.
After incubating for 4 days, the number of surviving colonies in each medium (No. 1-24) was counted, compared with the blank (No. 13), and antibacterial activity was evaluated according to the above “standard for antibacterial activity evaluation”.

<< Group without light irradiation (No. 13 to 24) >>
In the group without light irradiation (Nos. 13 to 24), the antibacterial activity evaluation was “−” regardless of the addition amount of methylene blue and the additive, and no antibacterial activity was observed.

<< Group with light irradiation (No. 1-12) >>
The group not containing methylene blue (No. 1, 4, 7, 10; group to which a methylene blue solution having a concentration of 0 w / v% was added) had an antibacterial activity evaluation of “−”, and no antibacterial activity was observed.
The group containing methylene blue (No. 2, 3, 5, 6, 8, 9, 11, 12; a group to which a methylene blue solution having a concentration of 0.05 to 0.10 w / v% was added) had an antibacterial activity evaluation of “ 4+ "or" 5+ "and antibacterial activity was observed.
When the methylene blue concentration is the same in the group containing methylene blue, it contains D-histidine as compared to the group not containing D-histidine (groups to which a 0-M concentration D-histidine aqueous solution was added; No. 2, 3). Group (group to which an aqueous solution of D-histidine having a concentration of 0.01 to 0.05 M was added; No. 5, 6, 8, 9, 11, 12) has high antibacterial activity evaluation, and antibacterial activity by addition of D-histidine (No. 5 with respect to No. 2 etc.) was observed.

<Example 5> When a proton donor (L-histidine) is added as an additive Bacterial fluid (20 μL), methylene blue solutions (100 μL) having various concentrations shown in Table 5, and D-histidine aqueous solutions having various concentrations shown in Table 5 (10 μL) is mixed to prepare a bacteria / reagent mixed solution (130 μL), and immediately after adding the entire amount (130 μL) to Helicobacter agar medium (Nissui Pharmaceutical Co., Ltd.) Left in the dark for 5 minutes.
After standing for 5 minutes, the cells were cultured in an incubator at 37 ° C. for 4 days with or without irradiation with LED light (wavelength 660 nm, projection amount 15 J / m ² ) for 4 minutes.
After incubating for 4 days, the number of surviving colonies in each medium (No. 1 to 8) was counted, compared with the blank (No. 5), and antibacterial activity was evaluated according to the above “standard for antibacterial activity evaluation”.

<< Group without light irradiation (No. 5 to 8) >>
In the group without light irradiation (No. 5 to 8), the antibacterial activity evaluation was “−” regardless of the addition amount of methylene blue and the additive, and the antibacterial activity was not recognized.

<< Group with light irradiation (No. 1-4) >>
The group containing no methylene blue (No. 1, 3; group to which a methylene blue solution having a concentration of 0 w / v% was added) had an antibacterial activity evaluation of “−”, and no antibacterial activity was observed.
The group containing methylene blue (No. 2, 4; group to which a methylene blue solution having a concentration of 0.10 w / v% was added) had an antibacterial activity evaluation of “4+” or “5+”, and antibacterial activity was recognized.
In a group containing methylene blue, a group containing L-histidine (a concentration of 0.01 M L-) was compared to a group containing no L-histidine (a group to which an L-histidine aqueous solution having a concentration of 0 M was added; No. 2). The group to which the histidine aqueous solution was added; No. 4) had a high antibacterial activity evaluation, and the enhancement of the antibacterial activity by adding D-histidine was recognized.

  From the above results, it was clarified that methylene blue alone has bactericidal activity, but that the bactericidal activity is further improved by adding an additive. In addition, all the additives are pharmaceutically acceptable and have safety equivalent to or higher than that of methylene blue alone.

DESCRIPTION OF SYMBOLS 10 Sterilization system 11 Endoscope 12 Calculation / control apparatus 13 Light source apparatus 14 Air supply / water supply apparatus 14a Air supply pump 14b Wash water tank 15 Liquid supply apparatus 16 Insertion part 16a Tip part 16b Bending part 16c Flexible pipe part 17 18 Universal cord 20 End cap 21 Observation window 22a Illumination window 22b Illumination window 23 Forceps outlet 24 Water jet outlet (WJ outlet)
25 Injecting nozzle 26 Forceps inlet 27 Mode changeover switch 28 Up / down bending angle knob 29 Left / right bending angle knob 30 Air / water supply button 31 Zoom operation section 32 Connector 33 Monitor 35 Liquid supply tank 36 Liquid supply body 37 Liquid supply pump 38 Foot switch 39 Liquid feed pipe 40 Connecting pipe 41a, 41b Light guide 42 Forceps tube 43 Air / water feed tube 44 Multi-core cable 44a Signal cable 44b Outer skin 45 Water jet tube (WJ tube)
47b Second WJ path 51 Screw tube 52 Net 53 Rubber 100 Sterilization system 101 Operation control unit 102 Imaging unit 102a Imaging port 103 Imaging direction control unit 104 Light irradiation unit 104a Light irradiation port 105 Irradiation direction control unit 106 Composition injection unit 106a Injection port 107 injection direction control means 108, 109, 110, 111, 112, 113 signal transmission path 200 subject 201 skin or mucous membrane 202 lesion part 203 composition adhesion region

Claims (12)

A composition for photodynamic therapy for use in photodynamic therapy for treating a Helicobacter pylori infection by contacting the Helicobacter pylori existing at a lesion site of the Helicobacter pylori infection and irradiating the Helicobacter pylori with light. ,
With methylene blue,
Comprising at least one pharmaceutically acceptable additive selected from the group consisting of osmolytes, reducing agents and proton donors,
The osmolyte is mannitol, the reducing agent is ascorbic acid, and the proton donor is histidine,
A composition for photodynamic therapy which does not contain parabens.   The composition for photodynamic therapy according to claim 1, wherein the light is white light, LED light having a wavelength of 660 ± 10 nm, or laser light. Light projection amount of the light is 1~200J / cm ^2, according to claim 1 or photodynamic therapy composition according to 2. A composition for photodynamic therapy for use in photodynamic therapy for treating the mucocutaneous infection by contacting the pathogenic microorganism with a pathogenic microorganism present at the lesion site of the mucocutaneous infection and irradiating the pathogenic microorganism with light. And
With methylene blue,
And at least one pharmaceutically acceptable additive selected from the group consisting of osmolyte and a reducing agent,
The osmolyte is mannitol, and the reducing agent is ascorbic acid,
A composition for photodynamic therapy which does not contain parabens.   The composition for photodynamic therapy according to claim 4, wherein the light is white light, LED light having a wavelength of 660 ± 10 nm, or laser light. Light projection amount of the light is 1~200J / cm ^2, photodynamic therapy composition according to claim 4 or 5. Means for contacting the photodynamic therapy composition according to any one of claims 1 to 3 with H. pylori,
A Helicobacter pylori sterilization system comprising means for irradiating the H. pylori with white light, LED light having a wavelength of 660 ± 10 nm or laser light. The sterilization system for Helicobacter pylori according to claim 7, wherein the amount of light projection of the white light, LED light having a wavelength of 660 ± 10 nm or laser light is 1 to 200 J / cm ² . Means for bringing the composition for photodynamic therapy according to any one of claims 4 to 6 into contact with a pathogenic microorganism of a mucocutaneous infection;
A sterilizing system for pathogenic microorganisms of skin mucosal infections, comprising means for irradiating the pathogenic microorganisms with white light, LED light having a wavelength of 660 ± 10 nm or laser light. The light projection of LED light or laser light of the white light or the wavelength 660 ± 10 nm is 1~200J / cm ^2, sterilization system of pathogenic microorganisms mucocutaneous infections of claim 9. Imaging means, light irradiation means, composition injection means, imaging direction control 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, and the composition An injection direction control means for controlling the injection direction of the injection means, and an operation for controlling 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 or mucocutaneous infection, comprising a control unit,
(a) The imaging direction control unit and the irradiation direction control unit operate based on a control signal from the calculation / control unit so that the light irradiation unit illuminates the observation area of the imaging unit,
(b) The imaging means, based on a control signal from the calculation / control unit, images the skin / mucous membrane, and transmits a video signal to the calculation / control unit,
(c) The calculation / control unit receives the video signal transmitted from the imaging unit, 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 injecting means injects the composition for photodynamic therapy according to any one of claims 1 to 6, based on a control signal from the calculation / control unit,
(f) 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 or mucocutaneous infection. Imaging means, light irradiation means, composition injection means, imaging direction control 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, and the composition An injection direction control means for controlling the injection direction of the injection means, and an operation for controlling 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 method of operating a sterilization system for lesions caused by Helicobacter pylori infection or mucocutaneous infection, comprising a control unit,
(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) The imaging means, based on a control signal from the calculation / control unit, images the skin / mucous membrane, 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, and the normal part and the lesioned part 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) the step of injecting the composition for photodynamic therapy according to any one of claims 1 to 6, wherein the composition injection means is based on a control signal from the calculation / control unit;
(f) activating the irradiation direction control means based on a control signal from the calculation / control section so as to match the irradiation direction of the light irradiation means with the lesioned part; and
(g) Helicobacter pylori infection or skin mucosal infection, wherein 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. Method of sterilization system for lesions caused by infectious diseases.