Fluorescent fibrous body and method for producing fluorescent fibrous body

Abstract

To provide a simple and highly sensitive method of preventing accidents where gauze or the like is left behind in a surgical operation, and to provide a fluorescent-emitting marker for facilitating surgical operations.SOLUTION: The present invention provides a fluorescent fiber body wherein a compound represented by formula (1) of the present invention or a salt thereof is bound to a fiber of a fibrous body selected from the group consisting of cellulose-based fibrous bodies, polyurethane fibrous bodies, animal hair fibrous bodies, silk fibrous bodies, acetate-based fibrous bodies, aliphatic polyamide fibrous bodies, and acrylic-based fibrous bodies.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a fluorescent fiber body and a method for manufacturing the fluorescent fiber body. According to the present invention, it can be effectively used in surgery using a fluorescence imaging system (FIS).

Background Art

[0002] Gauze and medical instruments used in surgery have been left in the body after surgery and reported as accidents. As a method to prevent this, gauze woven with metal wires is generally used, and after the operation, the patient is irradiated with X-rays and the fluoroscopic image is observed. Also, when confirming the position in the body of a medical instrument inserted and left in the patient's body, it is performed by irradiating the patient with X-rays and observing the fluoroscopic image. However, these methods have the problem that the surgeon and the patient are continuously exposed to X-rays during the operation. There is also a problem that it is difficult to use for medical instruments made of fibers or resins that transmit X-rays. On the other hand, as laparoscopic surgery and robotic surgery become mainstream in surgery, fluorescence imaging systems (FIS) that match the excitation / emission wavelengths of indocyanine green (ICG), a near-infrared fluorescent dye, are being standardly equipped in operating rooms. More recently, a fluorescence imaging system called a Medical Imaging Projection System (MIPS) surgical support device that can project surgical guidance information directly onto the patient's body surface and organs in real time by applying projection mapping technology has been put into practical use.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Non-Patent Documents

[0004]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] In order to prevent the above surgical accidents, Patent Document 1 discloses a method of attaching a phosphor marker to a gauze, exciting it with near-infrared light, and detecting the emitted light with a camera. However, in order to detect the emitted light with a camera, it was necessary to introduce new equipment. Furthermore, sufficient sensitivity could not be obtained by the method of Patent Document 1. In addition, Patent Documents 2 and Non-Patent Document 1 describe treating sponges with ICG. However, sufficient fluorescence could not be obtained by these treatments. An object of the present invention is to provide a method for simply and highly sensitively preventing the remaining accident of gauze or the like in a surgical operation. In addition, as a fluorescently emitting label (marker) for obtaining anatomical position information for smoothly performing the operation and accurately guiding (guiding) the progress direction of the operation, it can be temporarily adhered to the affected tissue of the patient, or It is to provide medical devices (gauze, sponge, stent, catheter, tube, surgical thread, etc.) made of various fibrous bodies that can be temporarily inserted and retained in the patient's body for use. Furthermore, it is to provide medical devices with high dye fastness that do not easily leak fluorescent dyes from these medical devices.

Means for Solving the Problems

[0006] As a result of intensive research on a simple and highly sensitive method for preventing the accidental retention of gauze or the like during surgery, the present inventors have found that by using a fluorescent fiber body obtained by staining a fiber body such as gauze with a specific fluorescent substance, it is possible to simply and surely prevent the accidental retention of gauze or the like during surgery. Further, by using a fluorescent fiber body stained with a specific fluorescent compound as gauze, a sponge, or various medical instruments, it can be temporarily inserted and retained in a patient's body for use, and it can be used as a fluorescent label (marker) for obtaining anatomical position information for smoothly performing surgery and accurately guiding (guiding) the progress direction of the surgery. The present invention is based on such findings. Therefore, the present invention provides [1] The following formula (1):

Chemical formula

Chemical formula

Effect of the Invention

[0007] According to the fluorescent fibrous material of the present invention, in a surgical operation using a fluorescence imaging system (FIS), it is possible to easily and highly sensitively prevent the remaining accident such as gauze, and it can also be used as a fluorescence guide. According to the present invention, even when the fluorescent fibrous material is located inside or on the back side of an organ, if the tissue thickness is 15 mm or less, it can be easily detected by FIS. Further, the fluorescent fibrous material of the present invention does not easily leak a fluorescent dye in the body during a surgical operation.

Brief Description of the Drawings

[0008]

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[0009] [1] Fluorescent Fiber Body The fluorescent fiber body of the present invention has the following formula (1): [Chemical Formula] (In the formula, R 1 is independently -(CH2)n-R 3 respectively, and R 2is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a carboxyl group, a sulfonyl group, or an amide group, and R 3 is -SO3 - or -CO-R 4 wherein R 4 is an oxygen atom, -O-(CH2)m-R 5 or -NH-(CH2)m-R 5 wherein m is an integer of 0 to 3, and R 5 is a dioxopyrrolidine group which may have a substituent, an alkyne group having 3 to 5 carbon atoms, an amino group, or an azide group (-N 3 ) and any one of R 1 is -(CH2)n-SO3 - wherein n is an integer of 3 to 10.) The compound represented by the formula (1) or a salt thereof is bonded to the fibers of a fibrous material selected from the group consisting of a cellulose-based fibrous material, a polyurethane fibrous material, an animal hair fibrous material, a silk fibrous material, an acetate-based fibrous material, and an aliphatic polyamide fibrous material. The bonding between the fibrous material and the compound represented by the formula (1) is not limited and may be a chemical bond or a physical bond, but a chemical bond is preferred. Here, the chemical bond means that the compound represented by the formula (1) forms a bond with the fibrous material surface by electrostatic interaction. The electrostatic interaction refers to hydrogen bonding, ionic interaction (ionic bond), etc. Also, the physical bond means that the compound represented by the formula (1) forms a bond with the fibrous material surface by physical adsorption by van der Waals force. In addition, there may be a portion where the compounds represented by the formula (1) are bonded to each other, for example, by hydrogen bonding or the like, and two or more molecules are stacked.

[0010] 《Compound of formula (1)》 The compound represented by formula (1) used in the present invention (hereinafter sometimes referred to as compound A) is a fluorescent compound (fluorescent substance) that exhibits an emission spectrum in the near-infrared wavelength region. Compound A is indocyanine green (hereinafter sometimes referred to as ICG), or an indocyanine derivative. This compound A is excited by long-wavelength visible light or near-infrared light (wavelength: 650 to 810 nm), and emits fluorescence of near-infrared light with a longer wavelength. For example, ICG is a fluorescent dye used in medical diagnosis, and suitable excitation wavelengths are 730 to 810 nm, and emission wavelengths are 780 to 880 nm. ICG is currently the only near-infrared fluorescent substance approved for use in humans, and is widely used in cardiac output, liver function, measurement of blood flow in the liver or stomach, ophthalmic angiography, or cerebral angiography.

[0011] Compound A is considered to emit fluorescence mainly due to a structure in which two benzoindole rings sandwich a polyene chain. That is, R 1 and R 2 groups are presumed not to have a great influence on the fluorescence color development, and are presumed to affect properties such as the hydrophilicity and hydrophobicity of compound A.

[0012] The two Rs of compound A 1 are each independently -(CH2)n-R 3 where R 1 is not limited, but gives compound A hydrophilic properties. n is an integer of 3 to 10, and is not limited, but when n is 3 or more, the hydrophobicity of compound A becomes stronger.

[0013] R 3 is -SO3 - , or -CO-R 4 where one of R 1 is -(CH2)n-SO3 - . Without limitation, having -SO3 - enhances the hydrophilicity of compound A and greatly improves its solubility in water. R 4 is an oxygen atom, -O-(CH2)m-R 5、or -NH-(CH2)m-R 5 is. R 4 is an oxygen atom or a group having -O- or -NH-. An alkylene group having 1 to 3 carbon atoms may be bonded to -O- or -NH-, but it may not have an alkylene group. That is, m in -(CH2)m- bonded to -O- or -NH- is an integer of 0 to 3. R 5 is a dioxopyrrolidine group which may have a substituent, an alkyne group having 3 to 5 carbon atoms, an amino group, or an azide group (-N 3 ). Examples of the dioxopyrrolidine group include the following formula:

Chemical formula

[0014] R 2 is, but is not limited to, a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a carboxyl group, a sulfonyl group, or an amide group.

[0015] The salt of the compound A is a salt with an inorganic base or an organic base, etc., and is not limited as long as it can be used for dyeing the fibrous body of the present invention. Specific examples of the salt with an inorganic base or an organic base, etc. include salts with an inorganic base, an organic base, or a metal alkoxide. It can be produced by mixing the compound A with an inorganic base, an organic base, or a metal alkoxide. Examples of inorganic bases capable of forming salts include hydroxides, carbonates, bicarbonates, acetates, or hydrides of alkali metals (such as lithium, sodium, or potassium, etc.); hydroxides or hydrides of alkaline earth metals (such as magnesium, calcium, or barium). Examples of organic bases capable of forming salts include dimethylamine, triethylamine, piperazine, pyrrolidine, piperidine, 2-phenylethylamine, benzylamine, ethanolamine, diethanolamine, pyridine, or collidine, etc. Examples of metal alkoxides include sodium methoxide, potassium tert-butoxide, or magnesium methoxide, etc. Preferred salts of Compound A include lithium salts, sodium salts, potassium salts, calcium salts, magnesium salts, or combinations thereof. In addition, specific salts with acids include salts with inorganic acids or organic acids. Examples of inorganic acids capable of forming salts include hydrochloric acid, sulfuric acid, nitric acid, etc., and examples of organic acids include acetic acid, dichloroacetic acid, trifluoroacetic acid, etc.

[0016] Specific examples of Compound A or its salts include the following compounds.

Chemical formula

[0017] 《Fiber body》 The fiber body used in the fluorescent fiber body of the present invention is not limited, and examples include cellulose-based fiber bodies, polyurethane fiber bodies, animal hair fiber bodies, silk fiber bodies, acetate-based fiber bodies, and aliphatic polyamide fiber bodies. The cellulose-based fiber body is a fiber body mainly containing plant-derived cellulose represented by the following formula or regenerated cellulose obtained by chemically regenerating the same and fiberizing it, and examples include cotton, hemp, rayon, cupra, or lyocell, etc.

Chemical formula

[0018] The polyurethane fiber body is a fiber body mainly composed of a polymer having a urethane bond. Polyurethane is generally a polymer compound in which an isocyano group and an alcoholic hydroxyl group react to form a urethane bond, and is represented by the following formula.

Chemical formula

[0019] The animal hair fiber body is a fiber body mainly composed of keratin basically made from animal hair, and examples include, but are not limited to, wool, cashmere, mohair, angora, or alpaca hair.

[0020] The silk fiber body is a fiber body made from an animal fiber mainly composed of polyamino acids (polypeptides·proteins) basically taken from insect cocoons or spiders, etc., and examples include, but are not limited to, silk made from the cocoons of silkworms.

[0021] The acetate fiber body is basically a fiber body made from acetyl cellulose obtained by reacting wood pulp with acetic anhydride. Although not limited, examples include diacetate represented by the following formula and triacetate in which all hydroxyl groups are acetylated.

Chem.

[0022] Aliphatic polyamide fiber bodies are generally called nylon and are fiber bodies mainly composed of polymers having aliphatic amide bonds. Examples of nylon fiber bodies include nylon 6 and nylon 6,6 represented by the following formula.

Chem.

[0023] Acrylic fiber bodies are fiber bodies mainly containing polyacrylonitrile represented by the following formula. In addition to polyacrylonitrile, examples include copolymers of acrylonitrile and vinyl chloride, sodium styrene sulfonate, or sodium methallyl sulfonate.

Chem.

[0024] 《Embodiment》 The fluorescent fiber body of the present invention can be produced by (1) a method of attaching the compound or a salt thereof to the fiber body in a solution state and then subjecting the fiber body to steam heat treatment, (2) a method of subjecting the fiber body to steam heat treatment while attaching the compound or a salt thereof to the fiber body in a solution state, or (3) a method of subjecting the fiber body to steam heat treatment while attaching the compound or a salt thereof to the fiber body in a solution state and then further subjecting it to steam heat treatment. These production methods will be described in detail in the production method of the fluorescent fiber body described below. These three embodiments are, namely, Embodiment 1 in which Compound A is bonded to the fiber body in a solution state and then steam heat treatment is performed, Embodiment 2 in which Compound A is attached to the fiber body in a solution state while performing steam heat treatment, and Embodiment 3 in which Compound A is attached to the fiber body in a solution state while performing steam heat treatment and then further steam heat treatment is performed. The fluorescent fiber body of the present invention exhibits excellent emission intensity due to the above three embodiments.

[0025] 《Emission intensity》 The fluorescent fiber body of the present invention emits fluorescence of near-infrared light with a long wavelength of about 800 to 880 nm when excited by near-infrared light (for example, 730 to 810 nm). The emission intensity of the fluorescent fiber body of the present invention is not particularly limited, but can be measured and calculated by the following method. Cut out the unstained fibrous body and the stained fluorescent fibrous body into squares with sides of 1.5 cm. Here, when the fibrous body has a large mesh and the irradiation light easily passes through, multiple sheets are used by stacking them. Next, place the unstained fibrous body inside the integrating sphere of an absolute luminescence quantum yield measuring device (Hamamatsu Photonics, C9920-02), and obtain the emission spectrum when irradiated with near-infrared light (center wavelength 730 nm) guided by an optical fiber from an LED light source (observation wavelength range 600 - 960 nm). Here, components of 785 nm or more contained in the near-infrared light are blocked by a low-pass filter (Semrock, BSP01-785R). Since the unstained fibrous body does not emit fluorescence in the observation wavelength range, only the emission peak derived from the irradiation light centered at 730 nm is observed in the obtained emission spectrum. Next, for the fluorescent fibrous body, measure the emission spectrum in the same way. An emission peak derived from the irradiation light is observed near 730 nm, and a fluorescence peak derived from the phosphor is observed near 830 nm. Here, using the intensity of the former peak as a reference, obtain a reference spectrum by normalizing the emission peak derived from the irradiation light in the emission spectrum of the unstained fibrous body. Finally, subtract this reference spectrum from the emission spectrum of the fluorescent fibrous body to obtain the emission difference spectrum of only the fluorescent fibrous body, and set the peak intensity in the wavelength range of 800 - 960 nm of this spectrum as the emission intensity χ. Here, the emission intensity is in arbitrary units in the above absolute luminescence quantum yield measuring device.

[0026] 《Quantum Yield》 The luminescence quantum yield is defined as the value obtained by dividing the number of photons absorbed by the sample by the number of photons emitted from the sample. The number of absorbed photons is taken as the value obtained by subtracting the spectral area of the irradiation light observed in the emission spectrum of the fluorescent fibrous body from the spectral area of the irradiation light observed in the emission spectrum of the unstained fibrous body, and the intensity of each spectrum is taken as the integrated value in the wavelength range of 670 - 800 nm. Next, the number of emitted photons is taken as the integrated value in the wavelength range of 800 - 950 nm in the emission spectrum of only the fluorescent fibrous body. Using the values calculated as above, calculate the quantum yield, and multiply the obtained value by 100 to obtain the quantum yield Φ (unit: %).

[0027] 《Fluorescence Imaging System》 The fluorescent fiber body of the present invention can be used for surgical operations using a fluorescence imaging system (hereinafter sometimes referred to as FIS). FIS is a device that helps surgeons accurately perform operations while viewing real-time images during surgery by visualizing biological tissues using fluorescence emission from a fluorescent substance, and is composed of a light-emitting element in the near-infrared wavelength range, a fluorescence camera, a fluorescence microscope, a fluorescence endoscope, and the like. As shown in Fig. 13, by using FIS, it is possible to selectively use modes such as a fluorescent green mode, a fluorescent blue / orange mode, or a fluorescent black-and-white mode, and capture the fluorescent fiber body with high sensitivity. That is, it is possible to efficiently detect the fluorescence color development of the fluorescent fiber body of the present invention during surgical operations. Furthermore, by using FSI, it is also possible to detect the fluorescent fiber body on the back side of an organ, and it is possible to simply and highly sensitively prevent the remaining accident of gauze or the like during surgical operations. More recently, a fluorescence imaging system called a MIPS surgical support device that applies projection mapping technology and can directly project surgical guidance information onto the body surface or organs of a patient in real time has been put into practical use. MIPS is composed of a head unit (lighting device, camera, projector, etc.) and a stand (control device, monitor, etc.), and can visualize the fluorescence distribution area by performing image conversion processing on the fluorescence information from ICG captured by an infrared light camera and projecting the image onto the affected part of the patient using projection mapping technology.

[0028] [2] Method for manufacturing the fluorescent fiber body The method for manufacturing the fluorescent fiber body of the present invention is (A) The following formula (1): [Chemical formula] (In the formula, R 1 are each independently -(CH2)n-R 3 , and R 2 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a carboxyl group, a sulfonyl group, or an amide group, and R 3 is -SO3 - , or -CO-R 4 and R4 is an oxygen atom, -O-(CH2)m-R 5 , or -NH-(CH2)m-R 5 , where m is an integer from 0 to 3, and R 5 is a dioxopyrrolidine group which may have a substituent, an alkyne group having 3 to 5 carbon atoms, an amino group, or an azide group (-N 3 ), and any one of R 1 is -(CH2)n-SO3 - , where n is an integer from 3 to 10.) A step of attaching a compound represented by the formula to a fibrous material selected from the group consisting of a cellulose-based fibrous material, a polyurethane fibrous material, an animal hair fibrous material, a silk fibrous material, an acetate-based fibrous material, and an aliphatic polyamide fibrous material in a solution state is included. The compound of formula (1) and the fibrous material can be used without being limited to the compound A and the fibrous material described in the above "[1 Fluorescent Fibrous Material]".

[0029] 《Compound Attachment Step (A)》 In the compound attachment step (A), the compound A represented by the above formula (1) is attached to a cellulose-based fibrous material, a polyurethane fibrous material, an animal hair fibrous material, a silk fibrous material, an acetate-based fibrous material, or an aliphatic polyamide fibrous material in a solution state. Specifically, the compound attachment step (A) is a step of dyeing the above fibrous material with the compound A.

[0030] (Solution Concentration) The solution concentration of the compound A in the compound attachment step (A) is not particularly limited, but is 1x10 -8 M to 1x10 -2 , preferably 1x10 -7 M to 1x10 -3 , and more preferably 1x10 -6 M to 5x10 -4 M. However, the solution concentration of the compound A can be appropriately adjusted according to the type of the compound, the type of the fibrous material, the dyeing conditions (temperature, pressure, time), the washing conditions (solvent or solution, temperature, time), and the drying conditions (temperature, humidity, time) so as to obtain sufficient luminescence intensity. The solvent for dissolving Compound A is not particularly limited, and examples thereof include water, saline, or water containing a small amount of ethyl alcohol. For example, the concentration of Compound A (e.g., ICG) in the compound adhesion step (A) is as described above, and as long as the fibrous body is dyed, the effects of the present invention can be obtained and are not limited. However, depending on the type of fibrous body, there is an optimal concentration range. The upper limit of the concentration is not limited as long as each fibrous body is dyed, and also depends on the cost of dyeing. Therefore, for example, as described above, in any fibrous body, it is 1x10 -2 M or less, and in some embodiments, it is 5x10 -3 M or less, and in some embodiments, it is 1x10 -3 M or less, and in some embodiments, it is 5x10 -4 M or less. The lower limit of the concentration can be appropriately selected by those skilled in the art from the description of the present specification. For example, the lower limit of the concentration of Compound A (e.g., ICG) in a cellulose-based fibrous body is 7.5x10 -7 M or more, and in some embodiments, it is 1.0x10 -6 M or more, and in some embodiments, it is 1.5x10 -6 M or more. The lower limit of the concentration of Compound A (e.g., ICG) in a polyurethane fibrous body is 1.5x10 -8 M or more, and in some embodiments, it is 5.0x10 -8 M or more, and in some embodiments, it is 1.5x10 -7 M or more. The lower limit of the concentration of Compound A (e.g., ICG) in a mammalian hair fibrous body is 1.5x10 -8 M or more, and in some embodiments, it is 5.0x10 -8 M or more, and in some embodiments, it is 1.5x10 -7 M or more. The lower limit of the concentration of Compound A (e.g., ICG) in a silk fibrous body is 1.5x10 -8 M or more, and in some embodiments, it is 5.0x10 -8 M or more, and in some embodiments, it is 1.5x10 -7 M or more. The lower limit of the concentration of Compound A (e.g., ICG) in the acetate fiber body is 1.5x10 -6 M or more, and in certain embodiments, it is 5.0x10 -6 M or more, and in certain embodiments, it is 1.5x10 -5 M or more. The lower limit of the concentration of Compound A (e.g., ICG) in the aliphatic polyamide fiber body is 1.5x10 -8 M or more, and in certain embodiments, it is 5.0x10 -8 M or more, and in certain embodiments, it is 1.5x10 -7 M or more. In each fiber body, the upper limit and the lower limit can be appropriately combined to form an optimal range.

[0031] (Time) The reaction time in the compound adhesion step (A) is not particularly limited as long as the dyeing is sufficiently carried out, and for example, it can be carried out in the range of 1 minute to 4 hours. The lower limit is 1 minute or more in certain embodiments, 3 minutes or more in certain embodiments, 5 minutes or more in certain embodiments, 10 minutes or more in certain embodiments, 20 minutes or more in certain embodiments, and 30 minutes or more in certain embodiments. The upper limit is 4 hours or less in certain embodiments, 3 hours or less in certain embodiments, 2 hours or less in certain embodiments, 1 hour or less in certain embodiments, 30 minutes or less in certain embodiments, and 20 minutes or less in certain embodiments. The upper limit and the lower limit can be appropriately combined. Also, the reaction time can be shortened when the reaction temperature described below is high, and can be lengthened when the reaction temperature is low.

[0032] (Temperature) The reaction temperature in the compound adhesion step (A) is not particularly limited as long as the dyeing is sufficiently carried out, but it can be carried out, for example, at 1°C to 100°C under atmospheric pressure. The lower limit is 1°C or higher in some embodiments, 10°C or higher in some embodiments, 20°C or higher in some embodiments, 30°C or higher in some embodiments, 40°C or higher in some embodiments, and 50°C or higher in some embodiments. The upper limit is 100°C or lower in some embodiments, 90°C or lower in some embodiments, 80°C or lower in some embodiments, 70°C or lower in some embodiments, and 60°C or lower in some embodiments. The above upper and lower limits can be appropriately combined. Also, the reaction temperature may be lowered when the reaction time is long, and can be increased when the reaction time is short.

[0033] A person skilled in the art can appropriately adjust the solution concentration, reaction time, and reaction temperature of the compound A according to the type of compound and the type of fibrous body so as to obtain sufficient luminescence intensity.

[0034] (Washing) The washing temperature and number of times in the compound adhesion step (A) are not particularly limited as long as the washing of ICG molecules with insufficient adhesion to the fibrous body is sufficiently carried out, but it can be carried out, for example, at 1°C to 100°C. The lower limit of the temperature is 1°C or higher in some embodiments, 10°C or higher in some embodiments, 20°C or higher in some embodiments, 30°C or higher in some embodiments, 40°C or higher in some embodiments, and 50°C or higher in some embodiments. The upper limit is 100°C or lower in some embodiments, 90°C or lower in some embodiments, 80°C or lower in some embodiments, 70°C or lower in some embodiments, and 60°C or lower in some embodiments. The above upper and lower limits can be appropriately combined. Also, the washing temperature may be increased when the reaction temperature is high, and can be lowered when the reaction temperature is low. Also, the number of times can be carried out within a range where a sufficient washing effect is obtained, that is, 1 to 10 times. The number of times is 1 time or more in some embodiments, 2 times or more in some embodiments, 3 times or more in some embodiments, 4 times or more in some embodiments, and 5 times or more in some embodiments. The washing water used for washing is not particularly limited, and examples thereof include water, physiological saline (low-concentration saline), or water containing a small amount of ethyl alcohol and / or a nonionic surfactant.

[0035] (Dehydration and drying) The dehydration and drying in the compound adhesion step (A) are not particularly limited as long as the water content contained in the fibrous body is dehydrated and dried to an equilibrium state with the working environment or below. For example, after dehydration with a centrifugal dehydrator, it can be placed in the atmosphere or in a state with a low saturated water vapor amount of 1 atm or less and carried out at 1°C to 100°C.

[0036] 《Steam heat treatment step (B)》 The steam heat treatment step (B) is a heat treatment (steam heat treatment) in high-temperature steam under pressure. The steam heat treatment can be carried out using, for example, an autoclave (high-pressure steam sterilizer). The steam heat treatment can be carried out at the saturated steam pressure at the set temperature. That is, in the steam heat treatment step (B), the fibrous body with compound A attached or the fibrous body to which compound A is to be attached in a solution state is steam heat-treated using an autoclave or the like.

[0037] (Temperature) The treatment temperature (set temperature) in the steam heat treatment step (B) is not limited, but is, for example, 105 to 150°C. The lower limit is 103°C or higher in some aspects, 105°C or higher in some aspects, 110°C or higher in some aspects, and 115°C or higher in some aspects. The upper limit is 150°C or lower in some aspects, 140°C or lower in some aspects, 130°C or lower in some aspects, and 125°C or lower in some aspects. The above upper and lower limits can be appropriately combined.

[0038] (Pressure) Since the pressure in the steam heat treatment step (B) is equal to the saturated steam pressure at the treatment temperature, it is 1.2 to 4.7 atm according to the above treatment temperature, preferably 1.5 to 3.3 atm, and preferably 2.0 to 2.9 atm.

[0039] (Time) The time in the steam heat treatment step (B) is not limited, but can be carried out, for example, in the range of 1 minute to 60 minutes. The lower limit is 1 minute or more in some embodiments, 3 minutes or more in some embodiments, 5 minutes or more in some embodiments, 10 minutes or more in some embodiments, 20 minutes or more in some embodiments, and 30 minutes or more in some embodiments. The upper limit is 60 minutes or less in some embodiments, 45 minutes or less in some embodiments, 30 minutes or less in some embodiments, 20 minutes or less in some embodiments, and 10 minutes or less in some embodiments. The above upper and lower limits can be appropriately combined.

[0040] (Washing, dehydration, drying) The conditions for washing, dehydration, and drying in the steam heat treatment step (B) may be the same as those in the compound adhesion step (A).

[0041] A person skilled in the art can appropriately adjust the pressure, time, and temperature of the steam heat treatment step (B) so that sufficient luminescence intensity can be obtained from the fibrous body after the dyeing, washing, dehydration, and drying steps, or after the dyeing and washing steps.

[0042] In the steam heat treatment of the present invention, after binding a water-soluble compound A (for example, indocyanine green (ICG)) to the fiber, the compound A can be firmly fixed to the fiber while suppressing the formation of aggregates. The water-soluble compound A (for example, ICG) can generally be adsorbed only in very small amounts on cellulose-based fibers such as cotton and diacetate. However, by the steam heat treatment of the present invention, it can be firmly adsorbed on fibers such as cotton. Therefore, by performing the steam heat treatment, the adsorption between ICG and the fiber becomes firm, and for example, during surgery, leakage of ICG into the surgical field can be prevented. If ICG leaks into the surgical field, the use of medical devices as a fluorescence guide in surgery is hindered. The fluorescent medical device obtained by the present invention can be effectively used as a guide in surgery.

[0043] 《Embodiment 1》 Embodiment 1 of the method for manufacturing the fluorescent fiber body of the present invention is an embodiment in which the above step (A) and the above step (B) are carried out in that order. In Embodiment 1, the compound adhesion step (A) and the steaming heat treatment step (B) may be carried out in that order. Further, after the compound adhesion step (A), it is preferable to wash the compound A that has not adhered to the fiber body. After finishing the dehydration and drying step in the compound adhesion step (B), if necessary, a sterilization treatment can be carried out. As the method of sterilization treatment, in addition to "high-pressure steam sterilization" using an autoclave commonly used in hospitals, there are "EOG sterilization" using ethylene oxide gas and "electron beam sterilization" using an electron beam. However, in order to ensure high safety, EOG sterilization and electron beam sterilization that enable sterilization treatment after product packaging are preferable.

[0044] 《Embodiment 2》 Embodiment 2 of the method for manufacturing the fluorescent fiber body of the present invention is an embodiment in which the dyeing treatment of the fiber body with compound A is carried out under high temperature and high pressure using a steaming heat treatment. The solution concentration, pressure, temperature, and time of compound A can use the conditions of the above compound adhesion step (A) and steaming heat treatment step (B). However, the conditions for obtaining sufficient emission intensity in 《Embodiment 1》 and the conditions for obtaining sufficient emission intensity in 《Embodiment 2》 are not necessarily the same.

[0045] 《Embodiment 3》 Embodiment 3 of the method for manufacturing the fluorescent fiber body of the present invention is an embodiment in which the fiber body obtained in Embodiment 2 is further carried out under high temperature and high pressure using a steaming heat treatment step (B2). The steaming heat treatment can use the conditions of the above steaming heat treatment step (B). However, the conditions for obtaining sufficient emission intensity in 《Embodiment 1》 or 《Embodiment 2》 and the conditions for obtaining sufficient emission intensity in 《Embodiment 3》 are not necessarily the same.

[0046] (Solution concentration) The solution concentration of compound A in Embodiment 2 or 3 is not particularly limited, but is 1x10 -7 M~1x10 -3 M, preferably 1x10 -6 M~1x10 -3 M, more preferably 1x10-5 M~5x10 -4 It is M. However, the solution concentration of Compound A can be appropriately adjusted according to the type of the compound and the type of the fibrous body so as to obtain sufficient luminescence intensity. The solvent for dissolving Compound A is not particularly limited, and examples thereof include water, physiological saline (low-concentration saline), or water containing a small amount of ethyl alcohol.

[0047] The pressure in Embodiment 2 or 3 is not limited, but is 1.2 to 4.7 atmospheres, preferably 1.5 to 3.3 atmospheres, and preferably 2.0 to 2.9 atmospheres.

[0048] (Temperature) The temperature in Embodiment 2 or 3 is not limited, but is, for example, 105 to 150 °C. The lower limit is 103 °C or higher in some embodiments, 105 °C or higher in some embodiments, 110 °C or higher in some embodiments, and 115 °C or higher in some embodiments. The upper limit is 150 °C or lower in some embodiments, 140 °C or lower in some embodiments, 130 °C or lower in some embodiments, and 125 °C or lower in some embodiments. The upper limit and the lower limit can be appropriately combined.

[0049] (Time) The time in Embodiment 2 or 3 is not limited, but can be carried out, for example, in 1 minute to 60 minutes. The lower limit is 1 minute or longer in some embodiments, 3 minutes or longer in some embodiments, 5 minutes or longer in some embodiments, 10 minutes or longer in some embodiments, 20 minutes or longer in some embodiments, and 30 minutes or longer in some embodiments. The upper limit is 60 minutes or shorter in some embodiments, 45 minutes or shorter in some embodiments, 30 minutes or shorter in some embodiments, 20 minutes or shorter in some embodiments, and 10 minutes or shorter in some embodiments. The upper limit and the lower limit can be appropriately combined. After finishing the drying step in Embodiment 2 or 3, sterilization treatment can be performed as necessary.

[0050] 《Function》 The mechanism by which the fluorescent fiber body of the present invention exhibits excellent fluorescence emission intensity has not yet been analyzed in detail, but can be estimated as follows. However, the present invention is not limited by the following description. In the present invention, Compound A is a fluorescent substance of ICG or an ICG derivative that emits near-infrared fluorescence. When the molecules constituting these substances aggregate in a liquid state or a solid state to form a so-called "aggregate", it is known that the generation of fluorescence becomes weak and the emission intensity decreases due to a phenomenon called "aggregation-induced quenching". When ICG or an ICG derivative adheres to the fiber body, at low concentrations, the molecules are less likely to aggregate and exhibit a relatively high emission intensity per molecule. However, since the number density of luminescent molecules is low, the emission intensity from the fiber body is insufficient. On the other hand, at high concentrations, the molecules may form aggregates while adhering to the fiber body. In this state, although the number density of molecules is high, the emission intensity decreases. As a result, it is necessary to search for optimal staining conditions. In addition, in the present invention, when such an aggregate exists on the fiber body and is subjected to steam heat treatment, the structure of the aggregate of ICG or an ICG derivative changes to be close to the single-molecule state, so the emission intensity recovers. Or it is presumed that the formation of aggregates is effectively suppressed during the dyeing treatment under high temperature and high pressure, and the emission intensity does not decrease. In the case of polyester-based fibers and acrylic-based fibers, even if steam heat treatment is performed, the fixation of ICG or an ICG derivative, which is a water-soluble dye, is not sufficient. This is presumably because the fiber structures of polyester-based fibers and acrylic-based fibers do not have polar groups or polar bonds such as the hydroxyl group (-OH group) possessed by cellulose-based fiber bodies and acetate-based fiber bodies, the urethane bond (-NH-CO-O- bond) possessed by polyurethane fiber bodies, and the amide bond (-NH-CO- bond) possessed by animal hair fiber bodies, silk fiber bodies, or aliphatic polyamide fiber bodies in their structures. Furthermore, the fluorescence of ICG or an ICG derivative is considered to be mainly obtained by a structure in which two benzoindole rings sandwich a polyene chain. Therefore, the R of the ICG derivative 1 and R 2The group is presumed not to have a significant effect on the fluorescence color development. Also, since the formation of the above-mentioned aggregates mainly originates from the structure in which two benzoindole rings sandwich a polyene chain, it is presumed that the ICG derivative also exhibits the same properties as ICG.

[0051] In addition, this specification [1] The following formula (1):

Chemical formula

Examples

[0052] Hereinafter, the present invention will be specifically described by reference examples and examples, but these do not limit the scope of the present invention.

[0053] 《Reference Examples 1 to 3》 In this reference example, using cotton gauze and an ICG aqueous solution (concentration: Reference Example 1: 5x10 -4 M, Reference Example 2: 5x10 -5 M, Reference Example 3: 5x10 -6 M), the compound adhesion step (A) was carried out, and a fluorescent fiber body was manufactured without performing the steaming heat treatment step (B). (Preparation) At room temperature, ICG aqueous solutions (staining treatment solutions) with concentrations of 1: 5x10 -4 M, 5x10 -5 M, 5x10 -6 M (where M represents the amount-of-substance concentration: mol / L) were prepared. ICG (molecular weight: 774.96, purchased from the Pharmaceutical and Medical Devices Regulatory Science Foundation, Inc.) was dissolved in distilled water immediately before the staining treatment and stirred with a stirrer until it was uniformly dissolved before use. Next, the mass of 2 pieces of "cotton gauze" (Shirokuma Shirasu, 12-fold folded, 7.5x7.5 cm, approximately 2.4 g / piece) used for staining was measured, and based on the bath ratio of 1:50, the mass of the ICG staining treatment solution was calculated from the weighed value of the cotton gauze. The staining treatment solution was weighed and placed in a glass bottle for staining treatment, and then the cotton gauze was immersed. Here, the bath ratio is the mass ratio of the cotton gauze to the staining treatment solution. (Staining) The above glass bottle was sealed with a lid and placed in a constant-temperature shaking water bath at room temperature filled with water (Yamato Scientific, BT-10 type shaking constant-temperature water bath). While shaking the bottle at a shaking speed of 80 rpm, the water temperature was heated to 80°C, and after reaching 80°C, it was shaken for 60 minutes. Then, it was transferred to an empty constant-temperature shaker and naturally cooled to room temperature while shaking. (Washing) The stained cotton gauze was immersed in another glass bottle filled with distilled water (bath ratio: 1:1000) and shaken at 40°C for 5 minutes for washing. The same operation was repeated 3 - 5 times by replacing the distilled water (the number of times was adjusted according to the concentration of the staining treatment solution). (Dehydration) The cotton gauze was taken out from the above glass bottle, sandwiched between thick blotting paper (Kimtowel), and pressed from top and bottom to dehydrate it. (Drying) It was transferred to a light-shielded low-humidity dryer (Samplatech Co., Ltd., Dry Keeper Auto C type) and dried at room temperature for 6 h - 24 h. As shown in Fig. 1A, the fluorescent fiber bodies of Reference Examples 1 to 3 emitted fluorescence centered around 830 nm upon excitation by near-infrared light (irradiation light) centered around 730 nm emitted from the light-emitting diode. Here, the state of fluorescence emission was photographed with a near-infrared camera, and the emission could not be confirmed with the naked eye.

[0054] The emission spectra and emission difference spectra of the obtained fluorescent fiber bodies (cotton gauze) of Reference Examples 1 to 3 were measured and defined as follows. First, the unstained fiber body and the fluorescent fiber bodies stained in Reference Examples 1 to 3 were cut out into squares with sides of 1.5 cm. Since the fiber bodies had large meshes and the irradiation light easily passed through, they were used in a double-layered manner. Next, the unstained fiber body was placed inside an integrating sphere (Hamamatsu Photonics, C9920-02), and the emission spectrum was obtained when irradiated with near-infrared light (wavelength 730 nm) guided by an optical fiber from an LED light source (observation wavelength range 600 to 960 nm). Since the unstained fiber body did not emit fluorescence in the observation wavelength range, only the emission peak derived from the irradiation light centered around 730 nm was observed in the obtained spectrum. Next, when the emission spectra of the cut-out fluorescent fiber bodies of Reference Examples 1 to 3 were measured in the same manner, an emission peak derived from the irradiation light around 730 nm and a fluorescence peak derived from the phosphor around 830 nm were observed. As a result, as shown in Fig. 1B, fluorescence coloring was observed at 800 to 960 nm.

[0055] The emission intensities of the obtained fluorescent fiber bodies of Reference Examples 1 to 3 were measured and calculated as follows. Here, with the former peak intensity as a reference, a reference spectrum was obtained by normalizing the emission peak derived from the irradiation light in the emission spectrum of the unstained fiber body. Finally, by subtracting this reference spectrum from the emission spectrum of the fluorescent fiber body, an emission difference spectrum of only the fluorescent fiber body was obtained. The peak intensity in the wavelength range of 800 to 960 nm of the obtained spectrum was defined as the emission intensity χ.

[0056] The quantum yields of the obtained fluorescent fiber bodies of Reference Examples 1 to 3 were measured and calculated as follows. The photoluminescence quantum yield is defined as the value obtained by dividing the number of photons emitted from the sample by the number of photons absorbed by the sample. The number of absorbed photons was determined as the difference between the spectral area of the irradiation light observed in the emission spectrum of the undyed fiber body and the spectral area of the irradiation light observed in the emission spectrum of the fluorescent fiber bodies of Reference Examples 1 to 3. The intensity of each spectrum was taken as the integrated value in the wavelength range of 670 to 800 nm. Next, the number of emitted photons was taken as the integrated value in the wavelength range of 800 to 950 nm in the emission spectrum of the fluorescent fiber body alone. Using the values calculated as described above, the quantum yield was calculated, and the value obtained by multiplying by 100 was defined as the quantum yield Φ (unit: %).

[0057] 《Reference Examples 4 - 8》 In this reference example, a compound attachment step (A) was performed using cotton gauze and an ICG aqueous solution, and a fluorescent fiber body was produced without performing a steaming heat treatment step (B). The concentration of the ICG aqueous solution was 4.5 x 10 -6 M (Reference Example 4), 1.5 x 10 -5 M (Reference Example 5), 4.5 x 10 -5 M (Reference Example 6), 1.5 x 10 -4 M (Reference Example 4), 4.5 x 10 -4 M (Reference Example 4), except that the operations of Reference Examples 1 to 3 were repeated to produce a fluorescent fiber body. For dehydration, the cotton gauze was taken out of the glass bottle and dehydrated using a high-speed rotary dehydrator (Alumis, APD - 6.0).

[0058] The emission spectra and emission difference spectra of the obtained fluorescent fiber bodies (cotton gauze) of Reference Examples 4 to 8 were measured and defined as in Reference Examples 1 to 3. As shown in Figure 2B, fluorescence coloring was observed at 800 to 960 nm.

[0059] The emission intensity and emission peak wavelength of the obtained fluorescent fiber bodies of Reference Examples 4 to 8 were measured and calculated as follows. Here, a reference spectrum was obtained by normalizing the emission peak derived from the irradiation light in the emission spectrum of the unstained fibrous body based on the peak intensity of the former. Finally, an emission difference spectrum of only the fluorescent fibrous body was obtained by subtracting this reference spectrum from the emission spectrum of the fluorescent fibrous body. The peak intensity in the wavelength range of 800 to 960 nm of the obtained spectrum was defined as the emission intensity χ, and the emission wavelength showing the peak intensity in the obtained difference spectrum was defined as the peak wavelength λ. As shown in the emission difference spectrum of Fig. 2C, a fluorescence coloration with a peak wavelength of 815 to 857 nm was observed. Among Reference Examples 4 to 8, the fluorescent fibrous body obtained at the solution concentration of 4.5x10 -5 M in Reference Example 6 showed the highest emission intensity and a peak wavelength of 829 nm. On the other hand, the fluorescent fibrous body obtained at the solution concentration of 4.5x10 -4 M in Reference Example 8 showed a weak emission intensity and a peak wavelength of 857 nm despite the high solution concentration. As described above, ICG is known to easily form aggregates in an aqueous solution or in a solid state. The peak wavelength of the monomer (one molecule) with high emission intensity is around 825 nm, while the aggregate called the J-aggregate shows a peak wavelength of 850 nm or more and its emission efficiency is reported to be low (Chem. Phys. Lett. Vol. 220, pp. 385 - 392 (1997)). That is, in Reference Example 8, it is considered that aggregates were formed in the aqueous solution or near the surface of the fluorescent fibrous body because the solution concentration was too high, thereby reducing the emission intensity of ICG. This indicates that there is an optimal solution concentration to obtain a strong emission intensity, and also indicates that the formation state of aggregates can be known from the peak wavelength of the emission spectrum.

[0060] The quantum yields of the obtained fluorescent fibrous bodies of Reference Examples 4 to 8 were measured and calculated in the same manner as in Reference Examples 1 to 3.

[0061] 《Reference Examples 9 - 15》 In this reference example, by a method for producing a fluorescent fibrous body that performs the compound adhesion step (A) and does not perform the steam heat treatment step (B), diacetate, cotton, nylon 66, polyester, acrylic fiber, wool, silk, and an ICG aqueous solution (7.5x10-5 A fluorescent fibrous body was produced using (M). A multifiber cloth (SDC; Shikisensha) in which these fibers were integrally sewn was used, and the concentration of the ICG aqueous solution was 7.5×10 -5 A fluorescent fibrous body was obtained by repeating the operations according to Reference Examples 4 to 8, except that it was M. As shown in FIG. 3, fluorescence emission with a peak wavelength of 820 to 920 nm was observed. In particular, in nylon 66, wool, and silk, since the peak wavelength exceeded 900 nm, it is strongly suspected that aggregates were formed as a result of thick adhesion and accumulation of ICG.

[0062] 《Examples 1 to 2》 In this example, according to Embodiment 1 of the method for producing the fluorescent fibrous body of the present invention, cotton gauze and an ICG aqueous solution (Example 4: 5×10 -4 M, Example 5: 5×10 -5 M) were used to produce a fluorescent fibrous body. The steps of (Preparation) to (Dehydration) are the same as those in Reference Examples 1 to 3. (Steam heat treatment) A predetermined amount of distilled water was placed in an autoclave (SK Medical Electronics Co., Ltd., Laboclave II / V type), and then the dyed cotton gauze was placed on a support fitting and subjected to steam heat treatment at 132° C. for 8 minutes. The step of (Drying) is the same as that in Reference Examples 1 to 3. As shown in FIG. 4A, the fluorescent fibrous bodies of Examples 1 to 2 emitted fluorescence centered around 830 nm by excitation with near-infrared light (irradiation light) centered around 730 nm emitted from a light-emitting diode.

[0063] The emission spectra, emission difference spectra, emission intensities, and quantum yields of the obtained fluorescent fibrous bodies of Examples 1 to 2 were obtained by the same operations as those in Reference Examples 1 to 3. As shown in FIG. 4B, fluorescence emission was observed at 800 to 960 nm.

[0064] 《Examples 3 to 7》 In this example, according to Embodiment 1 of the method for producing the fluorescent fibrous body of the present invention, a fluorescent fibrous body was produced using cotton gauze and an ICG aqueous solution. The concentration of the ICG aqueous solution was 4.5×10-6 M (Example 3), 1.5 x 10 -5 M (Example 4), 4.5 x 10 -5 M (Example 5), 1.5 x 10 -4 M (Example 6), 4.5 x 10 -4 Except for using M (Example 7), the operations of Examples 1 - 2 were repeated to produce the fluorescent fiber body.

[0065] As shown in Fig. 5C, fluorescence emission with a peak wavelength of 815 - 844 nm was observed. Among them, the fluorescent fiber body obtained at the solution concentration of 1.5 x 10 -4 M in Example 4 showed the highest emission intensity and a peak wavelength of 837 nm. Here, when comparing the emission intensity with Reference Examples 4 - 8, at low concentrations of 4.5 x 10 -6 M and 1.5 x 10 -5 M, the intensities of Examples 3 and 4 were lower than those of Reference Examples 4 and 5. However, at higher concentrations, Examples 5 - 7 exceeded Reference Examples 6 - 8, indicating that by adding the steam heat treatment step (B) following the compound adhesion step (A), it is possible to greatly improve the emission intensity. Especially on the high - concentration side, the effect of increasing the emission intensity is remarkable. Note that the steam heat treatment in Embodiment 1 can be replaced by the "steam sterilization treatment" (high - temperature and high - pressure steam treatment) performed before surgery in hospitals, etc. By subjecting the fluorescent fiber bodies produced in Reference Examples 1 - 15 to the "steam sterilization treatment", it is possible to obtain the same effect as in Embodiment 1.

[0066] 《Examples 8 - 9》 In this example, according to Embodiment 2 of the method for manufacturing the fluorescent fiber body of the present invention, cotton gauze and an ICG aqueous solution (Example 8: 5 x 10 -5 M, steam (high - temperature and high - pressure) dyeing time 10 minutes, Example 9: 5 x 10 -5 M, same time 20 minutes) were used to produce the fluorescent fiber body. The process of (Preparation) is the same as in the case of Reference Examples 1 - 3. (Steam heat treatment step (B)) A predetermined amount of distilled water was placed in an autoclave (SK Medical Electronics Co., Ltd., Labo Clave II / V type), and several zeolites for preventing bumping were added to the glass bottle for dyeing treatment containing the dyeing treatment liquid and cotton gauze. It was placed in the autoclave without a lid and steam heat-treated at 132 °C for 10 minutes or 20 minutes. The steps of (washing) to (drying) are the same as those in Reference Examples 1 to 3. As shown in Fig. 6A, the fluorescent fiber bodies of Examples 8 and 9 emitted fluorescence centered around 830 nm upon excitation by near-infrared light (irradiation light) centered around 730 nm.

[0067] The emission spectra, emission difference spectra, emission intensities, and quantum yields of the obtained fluorescent fiber bodies of Examples 8 and 9 were obtained by the same operations as in Reference Examples 1 to 3. As shown in Fig. 6B, fluorescence coloring was observed at 800 to 960 nm. As shown in Fig. 6C, the fluorescent fiber body obtained in Embodiment 2 showed excellent emission intensity. Although the emission intensity slightly decreased as the time of the steam heat treatment step (B) increased from 10 minutes to 20 minutes, as is clear from Examples 27 to 31 (Embodiment 2) and Examples 32 to 36 (Embodiment 3) shown below, when the time of the steam heat treatment step (B) exceeds 10 minutes, it has almost no effect on the emission intensity. Therefore, the time of the steam heat treatment step (B) in Embodiment 2 and Embodiment 3 was set based on 15 minutes.

[0068] 《Examples 10 to 15》 In this example, a fluorescent fiber body was produced using cotton gauze and an ICG aqueous solution according to Embodiment 2 of the method for producing a fluorescent fiber body of the present invention. Except that the concentration of the ICG aqueous solution was changed to 4.5x10 -6 M (Example 10), 1.5x10 -5 M (Example 11), 4.5x10 -5 M (Example 12), 1.5x10 -4 M (Example 13), 4.5x10 -4 M (Example 14), 1.5x10 -3 M (Example 15), the operations of Examples 8 to 9 were repeated to produce a fluorescent fiber body. Note that the steam heat treatment step (B) was set at 132°C for 15 minutes.

[0069] As shown in Fig. 7A, the fluorescent fiber bodies of Examples 10 to 14 emitted fluorescence centered around 830 nm by excitation with near-infrared light (irradiation light) centered around 730 nm. As shown in Fig. 7C, fluorescence coloring with a peak wavelength of 811 to 852 nm was observed. Among them, the fluorescent fiber body obtained at the solution concentration of 1.5×10 -4 M in Example 9 showed the highest emission intensity and a peak wavelength of 834 nm. Here, when compared with Examples 3 to 7 of Embodiment 1, although the emission intensity was lower, by performing the compound adhesion step (A) and the steam heat treatment step (B) simultaneously, the time required for the dyeing step was shortened to 1 / 6 or less.

[0070] 《Examples 16 to 20》 In this example, according to Embodiment 2 of the method for producing the fluorescent fiber body of the present invention, cotton gauze and an ICG aqueous solution (Example 8: 1×10 -5 M, Example 9: 2.5×10 -5 M, Example 10: 5.0×10 -5 M, Example 11: 7.5×10 -5 M, Example 12: 1.0×10 -4 M) were used to produce a fluorescent fiber body. The solution concentration of ICG was 1×10 -5 M to 1.0×10 -4 M, and except that the time of the steam heat treatment step (B) was 15 minutes, the operations of Examples 8 to 9 were repeated to obtain a fluorescent fiber body. The emission spectra, emission difference spectra, emission intensities, and quantum yields of the obtained fluorescent fiber bodies of Examples 16 to 20 were obtained by the same operations as in Reference Examples 1 to 3.

[0071] As shown in Fig. 8A, the fluorescent fiber bodies of Examples 16 to 20 emitted fluorescence centered around 830 nm by excitation with near-infrared light (irradiation light) centered around 730 nm. As shown in Fig. 8B, fluorescence coloring was observed at 800 to 960 nm. As shown in Fig. 8C, Examples 16 to 20 showed excellent emission intensities. In particular, Example 19 (7.5×10 -5The luminescence intensity of (M) was high.

[0072] 《Examples 21 - 26》 In this example, according to Embodiment 3 of the method for manufacturing the fluorescent fiber body of the present invention, the fluorescent fiber bodies obtained in Examples 10 - 15 were subjected to an additional steaming treatment (B2). The process of the steaming treatment step (B2) is the same as in the case of Embodiment 1 (Examples 3 - 7). As shown in Fig. 9A, the fluorescent fiber bodies of Examples 21 - 26 emitted fluorescence centered around 830 nm upon excitation by near-infrared light (irradiation light) centered around 730 nm emitted from the light-emitting diode. As shown in Fig. 9C, fluorescence coloring with a peak wavelength of 810 - 861 nm was observed. Among them, the fluorescent fiber body obtained at the solution concentration of 1.5x10 -4 M of Example 24 showed the highest luminescence intensity and a peak wavelength of 829 nm. Here, when comparing the luminescence intensity with Embodiment 2 (Examples 10 - 15), at a high concentration of 1.5x10 -4 M or more, Examples 24 - 26 exceeded Examples 13 - 15, indicating that by adding the steaming treatment step (B) to Embodiment 2, it is possible to further improve the luminescence intensity.

[0073] 《Examples 27 - 31》 In this example, according to Embodiment 2 of the method for manufacturing the fluorescent fiber body of the present invention, cotton gauze and an ICG aqueous solution (1.5x10 -4 M) were used to manufacture fluorescent fiber bodies with different steaming treatment step (B) times (Example 27: 10 minutes, Example 28: 20 minutes, Example 29: 30 minutes, Example 30: 45 minutes, Example 31: 60 minutes). Here, the steps of (preparation), (dyeing + steaming treatment), (washing) - (drying) are the same as in the case of Embodiment 2 (Examples 10 - 15). As shown in Fig. 10A, the fluorescent fiber bodies of Examples 27 - 31 showed fluorescence coloring with a peak wavelength of 834 - 843 nm upon excitation by near-infrared light (irradiation light) centered around 730 nm emitted from the light-emitting diode, and no significant difference was observed in their luminescence intensity. That is, when dyeing was performed in Embodiment 2, it can be said that the steaming treatment time does not significantly affect the luminescence characteristics of the fluorescent fiber body.

[0074] Examples 32 to 36 According to Embodiment 3 of the method for manufacturing the fluorescent fiber body of the present invention, an additional steaming heat treatment step (B2) was performed on the fluorescent fiber bodies obtained in Examples 27 to 31. The steaming heat treatment process is the same as in Embodiment 1 (Examples 3 to 7). As shown in FIG. 10B, in the fluorescent fiber bodies of Examples 32 to 36, fluorescence coloring with a peak wavelength of 824 to 833 nm was observed due to the excitation of near-infrared light (irradiation light) centered at 730 nm emitted from the light-emitting diode, and no significant difference was found in the emission intensity. That is, even when dyed in Embodiment 3, it can be said that the steaming heat treatment time does not significantly affect the emission characteristics of the fluorescent fiber body. Here, when comparing the emission intensity with Embodiment 2 (Examples 27 to 31), all of Examples 32 to 36 exceed Embodiment 2, indicating that by adding the steaming heat treatment step (B) to Embodiment 2, it is possible to further improve the emission intensity. Note that the steaming heat treatment in Embodiment 3 can be replaced by "steam sterilization treatment" (high-temperature and high-pressure steam treatment) performed before surgery in a hospital or the like. By subjecting the fluorescent fiber body manufactured in Embodiment 2 to "steam sterilization treatment", an effect equivalent to that of Embodiment 3 can be obtained. Looking at Examples 3 to 7, 10 to 15, and 21 to 36 manufactured according to Embodiments 1 to 3, when the emission intensity exceeds 120, the peak wavelength is all within the range of 834 ± 10 nm. Since the emission intensity decreases outside this range, a correlation between the emission intensity and the emission peak wavelength can be observed.

[0075] Leakage Test In the fluorescent fiber body produced by the manufacturing method of the present invention, the following leakage test was conducted to verify the adhesion stability (fastness) of ICG attached to the gauze in the human body. Cotton gauze and ICG aqueous solution (1.5x10 -4Using (M), at a bath ratio of 1:100, dyeing was carried out under the conditions of (1) only the adhesion step (A) (80 °C, 60 minutes), (2) Embodiment 1 (80 °C, 60 minutes + steam sterilization), (3) Embodiment 2 (132 °C, 15 minutes), and (4) Embodiment 3 (132 °C, 15 minutes + steam sterilization). After dehydration, they were washed once with an aqueous solution of a surfactant (Tween 20, Biomedical Science Co., Ltd.) (9.0×10 -5 mol·L -1 , bath ratio: 1:200) and three times with distilled water. Here, the liquid temperature of the washing solution was 50 °C, and dehydration was performed each time after washing. These fluorescent fiber bodies were immersed in an aqueous solution of human albumin physiological saline (5.0 wt%) simulating human body fluid at 37 °C and a bath ratio of 1:20. Using a visible ultraviolet spectrophotometer, the amount of ICG leaked from one piece of gauze into the immersion solution was measured over time until 8 hours later (Figure 11). It is known that albumin, which is a major component of plasma proteins, strongly binds to ICG at the molecular level. As a result, although the amount of leaked ICG was extremely small, it could be quantified with high sensitivity. The fluorescent fiber bodies of (1) only the adhesion step (A) continued to leak even after 8 hours, while the sample of (2) Embodiment 1, which was steam sterilized after that, leaked slightly until 1 hour later, but the amount was extremely small. Also, the fluorescent fiber bodies of (3) only Embodiment 2 continued to leak until 5 hours later, but the leakage amount was less than half of that of (1), and the sample of (4) Embodiment 3, which was steam sterilized after that, leaked slightly until 1 hour later, but the amount was extremely small. From these results, it became clear that by performing steam sterilization treatment after dyeing with an ICG aqueous solution, the ICG molecules attached to the fluorescent fiber bodies acquire extremely high adhesion stability (fastness).

[0076] 《Examples 37 - 41, Reference Examples 16 - 17》 In this example and reference example, according to Embodiment 1 of the method for producing the fluorescent fiber body of the present invention, diacetate (Example 37), cotton (Example 38), nylon 66 (Example 39), polyester (Reference Example 16), acrylic fiber (Reference Example 17), wool (Example 40), silk (Example 41) and an ICG aqueous solution (7.5×10 -5A fluorescent fiber body was produced using [[ID=]]. The use of a multifiber cloth in which these fibers are integrally sewn is the same as in Reference Examples 9 to 15. The steps of (Preparation) to (Dehydration) are the same as in Reference Examples 9 to 15. The steps of (Steam heat treatment) and (Drying) are the same as in Embodiment 1 (Examples 3 to 7). As shown in FIG. 12, fluorescence emission with a peak wavelength of 810 to 900 nm was observed. In particular, in nylon 66, wool, and silk, since the peak wavelength is 900 nm, the formation of aggregates is strongly suspected. The emission intensity of all the fluorescent fiber bodies in Examples 37 to 41 far exceeds that of Reference Examples 9 to 15, indicating that it is possible to greatly improve the emission intensity by adding a steam heat treatment step (B) following the compound adhesion step (A). In particular, in diacetate (Example 37), cotton (Example 38), nylon 66 (Example 39), and wool (Example 40), the effect of increasing the emission intensity is remarkable.

[0077] 《Examples 42 to 45, Reference Examples 18 to 19》 In this example and the reference example, according to Embodiment 2 of the method for producing the fluorescent fiber body of the present invention, diacetate (Example 42), cotton (Example 43), nylon 66 (Example 44), polyester (Reference Example 18), acrylic fiber (Reference Example 19), wool (Example 45) and an ICG aqueous solution (4.5x10 -5 A fluorescent fiber body was produced using [[ID=]]. The use of a multifiber cloth in which these fibers are integrally sewn is the same as in Reference Examples 9 to 15. The step of (Preparation) is the same as in Reference Examples 9 to 15. The step of (Dyeing + Steam heat treatment) is the same as in Embodiment 2 (Examples 10 to 15). The steps of (Washing) to (Drying) are the same as in Reference Examples 9 to 15. As shown in FIG. 13, fluorescence emission with a peak wavelength of 818 to 920 nm was observed, but almost no emission was detected in polyester and acrylic. On the other hand, the diacetate of Example 42 showed the highest emission intensity among them.

[0078] Examples 46 to 49, Reference Examples 20 to 21 In this Example and Reference Examples, according to Embodiment 2 of the method for producing a fluorescent fiber body of the present invention, diacetate (Example 46), cotton (Example 47), nylon 66 (Example 48), polyester (Reference Example 20), acrylic fiber (Reference Example 21), wool (Example 49) and an ICG aqueous solution (1.5x10 -5 M) were used to produce a fluorescent fiber body. The use of a multi-fiber cloth in which these fibers are integrally sewn is the same as in Reference Examples 9 to 15. The step of (Preparation) is the same as in Reference Examples 9 to 15. The step of (Dyeing + Heat Setting) is the same as in Embodiment 2 (the same as in Examples 10 to 15). The steps of (Washing) to (Drying) are the same as in Reference Examples 9 to 15. As shown in FIG. 14, fluorescence emission with a peak wavelength of 811 to 920 nm was observed. In polyester and acrylic, almost no emission was detected. On the other hand, nylon 66 of Example 48 showed the highest emission intensity.

[0079] Examples 50 to 53, Reference Examples 22 to 23 In this Example and Reference Examples, according to Embodiment 2 of the method for producing a fluorescent fiber body of the present invention, diacetate (Example 50), cotton (Example 51), nylon 66 (Example 52), polyester (Reference Example 22), acrylic fiber (Reference Example 23), wool (Example 53) and an ICG aqueous solution (1.5x10 -6 M) were used to produce a fluorescent fiber body. The use of a multi-fiber cloth in which these fibers are integrally sewn is the same as in Reference Examples 9 to 15. The step of (Preparation) is the same as in Reference Examples 9 to 15. The step of (Dyeing + Heat Setting) is the same as in Embodiment 2 (the same as in Examples 10 to 15). The steps of (Washing) to (Drying) are the same as in Reference Examples 9 to 15. As shown in Fig. 15, fluorescence emission with a peak wavelength of 812 - 846 nm was observed. However, in the case of diacetate, polyester, and acrylic, almost no emission was detected. On the other hand, nylon 66 of Example 52 and wool of Example 53 showed high emission intensity despite the low concentration of the ICG aqueous solution.

[0080] 《Examples 54 - 57, Reference Example 24 - 25》 In this example and reference example, according to Embodiment 2 of the method for manufacturing the fluorescent fiber body of the present invention, diacetate (Example 54), cotton (Example 55), nylon 66 (Example 56), polyester (Reference Example 24), acrylic fiber (Reference Example 25), wool (Example 57) and an ICG aqueous solution (7.5x10 -7 M) were used to produce a fluorescent fiber body. The point of using a multi - fiber cloth in which these fibers are integrally sewn is the same as in Reference Examples 9 - 15. The process of (Preparation) is the same as in Reference Examples 9 - 15. The process of (Dyeing + Heat Treatment) is the same as in Embodiment 2 (the same as in Examples 10 - 15). The processes of (Washing) - (Drying) are the same as in Reference Examples 9 - 15. As shown in Fig. 16, fluorescence emission with a peak wavelength of 813 - 829 nm was observed. However, in the case of polyester and acrylic, almost no emission was detected. On the other hand, nylon 66 of Example 56 and wool of Example 57 showed the highest emission intensity among those using the multi - fiber cloth in Embodiment 2 despite the low concentration of the ICG aqueous solution.

[0081] 《Examples 58 - 61, Reference Example 26 - 27》 In this example and reference example, according to Embodiment 2 of the method for manufacturing the fluorescent fiber body of the present invention, diacetate (Example 58), cotton (Example 59), nylon 66 (Example 60), polyester (Reference Example 26), acrylic fiber (Reference Example 27), wool (Example 61) and an ICG aqueous solution (4.5x10 -6 M) were used to produce a fluorescent fiber body. The point of using a multi - fiber cloth in which these fibers are integrally sewn is the same as in Reference Examples 9 - 15. (Preparation) process is the same as in Reference Examples 9 to 15. (Dyeing + Heat treatment) process is the same as in Embodiment 2 (the same as in Examples 10 to 15). (Washing) to (Drying) processes are the same as in Reference Examples 9 to 15. As shown in Fig. 17, fluorescence emission with a peak wavelength of 808 to 824 nm was observed. However, in polyester and acrylic, almost no emission was detected. On the other hand, nylon 66 of Example 60 and wool of Example 61 showed the highest emission intensity.

[0082] 《Examples 62 to 65, Reference Examples 28 to 29》 In this Example and Reference Examples, according to Embodiment 3 of the method for producing a fluorescent fiber body of the present invention, diacetate (Example 62), cotton (Example 63), nylon 66 (Example 64), polyester (Reference Example 28), acrylic fiber (Reference Example 29), wool (Example 65) and ICG aqueous solution (4.5x10 -5 M) were used to produce a fluorescent fiber body. The point of using a multifiber cloth in which these fibers are integrally sewn is the same as in Reference Examples 9 to 15. (Preparation) process is the same as in Reference Examples 9 to 15. (Dyeing + Heat treatment) process is the same as in Embodiment 3 (the same as in Examples 21 to 26). (Washing) to (Drying) processes are the same as in Reference Examples 9 to 15. As shown in Fig. 18, fluorescence emission with a peak wavelength of 812 to 914 nm was observed. In polyester and acrylic, almost no emission was detected. On the other hand, diacetate of Example 62 showed the highest emission intensity.

[0083] 《Examples 66 to 69, Reference Examples 30 to 31》 In this Example and Reference Examples, according to Embodiment 3 of the method for producing a fluorescent fiber body of the present invention, diacetate (Example 66), cotton (Example 67), nylon 66 (Example 68), polyester (Reference Example 30), acrylic fiber (Reference Example 31), wool (Example 69) and ICG aqueous solution (1.5x10 -5A fluorescent fiber body was produced using (M). The use of a multifiber cloth in which these fibers are integrally sewn is the same as in Reference Examples 9 to 15. The process of (Preparation) is the same as in the case of Reference Examples 9 to 15. The process of (Dyeing + Heat Setting) is the same as in Embodiment 2 (the same as in the case of Examples 21 to 26). The processes of (Washing) to (Drying) are the same as in the case of Reference Examples 9 to 15. As shown in Fig. 19, fluorescence emission with a peak wavelength of 807 to 896 nm was observed. In polyester and acrylic, almost no emission was detected. On the other hand, nylon 66 of Example 68 showed the highest emission intensity.

[0084] 《Examples 70 to 73, Reference Examples 32 to 33》 In this example and the reference example, according to Embodiment 3 of the method for producing a fluorescent fiber body of the present invention, diacetate (Example 70), cotton (Example 71), nylon 66 (Example 72), polyester (Reference Example 32), acrylic fiber (Reference Example 33), wool (Example 73) and an ICG aqueous solution (1.5x10 -6 A fluorescent fiber body was produced using (M). The use of a multifiber cloth in which these fibers are integrally sewn is the same as in Reference Examples 9 to 15. The process of (Preparation) is the same as in the case of Reference Examples 9 to 15. The process of (Dyeing + Heat Setting) is the same as in Embodiment 2 (the same as in the case of Examples 21 to 26). The processes of (Washing) to (Drying) are the same as in the case of Reference Examples 9 to 15. As shown in Fig. 20, fluorescence emission with a peak wavelength of 807 to 838 nm was observed. In polyester and acrylic, almost no emission was detected. On the other hand, nylon 66 of Example 72 and wool of Example 73 showed the highest emission intensity despite almost no emission from other fiber bodies.

[0085] 《Examples 74 to 77, Reference Examples 34 to 35》 In this example and the reference examples, according to Embodiment 3 of the method for manufacturing the fluorescent fiber body of the present invention, diacetate (Example 74), cotton (Example 75), nylon 66 (Example 76), polyester (Reference Example 34), acrylic fiber (Reference Example 35), wool (Example 77) and an ICG aqueous solution (7.5x10 -7 M) were used to produce a fluorescent fiber body. The use of a multi-fiber cloth in which these fibers are integrally sewn is the same as in Reference Examples 9 to 15. The process of (Preparation) is the same as in the case of Reference Examples 9 to 15. The process of (Dyeing + Heat Setting) is the same as in Embodiment 2 (the same as in the case of Examples 21 to 26). The processes of (Washing) to (Drying) are the same as in the case of Reference Examples 9 to 15. As shown in Fig. 21, fluorescence emission with a peak wavelength of 807 to 824 nm was observed, but almost no emission was detected in polyester and acrylic. On the other hand, nylon 66 of Example 76 showed the highest emission intensity among Embodiment 3 using a multi-fiber cloth.

[0086] 《Examples 78 to 81, Reference Examples 36 to 37》 In this example and the reference examples, according to Embodiment 3 of the method for manufacturing the fluorescent fiber body of the present invention, diacetate (Example 78), cotton (Example 79), nylon 66 (Example 80), polyester (Reference Example 36), acrylic fiber (Reference Example 37), wool (Example 81) and an ICG aqueous solution (4.5x10 -6 M) were used to produce a fluorescent fiber body. The use of a multi-fiber cloth in which these fibers are integrally sewn is the same as in Reference Examples 9 to 15. The process of (Preparation) is the same as in the case of Reference Examples 9 to 15. The process of (Dyeing + Heat Setting) is the same as in Embodiment 2 (the same as in the case of Examples 21 to 26). The processes of (Washing) to (Drying) are the same as in the case of Reference Examples 9 to 15. As shown in Fig. 22, fluorescence emission with a peak wavelength of 806 to 821 nm was observed, but almost no emission was detected in polyester and acrylic. On the other hand, nylon 66 of Example 80 and wool of Example 81 showed the highest emission intensity among them.

[0087] 《Example 82》 In this example, according to Embodiment 2 of the method for manufacturing the fluorescent fiber body of the present invention, cotton gauze and an ICG aqueous solution (1.5x10 -4 M) were used to manufacture a fluorescent fiber body at different steam heat treatment temperatures (121 °C). (Preparation, dyeing + steam heat treatment, washing to drying) steps are the same as those in Embodiment 2 (Example 13). As shown in Figs. 23A and 23B, the fluorescent fiber bodies of Example 82 and Example 13 showed fluorescence emission with a peak wavelength of 834 nm by excitation with near-infrared light (irradiation light) centered at 730 nm emitted from a light-emitting diode. The emission intensity was slightly higher for Example 47 dyed at 121 °C, but since a decrease in the fastness of ICG is a concern in the dyeing process at low temperatures, in the present invention, a standard steam heat treatment temperature of 132 °C was used in the steam sterilization treatment apparatus.

[0088] 《Examples 83 to 84, and Reference Example 38》 In this reference example and examples, according to the method for manufacturing the fluorescent fiber body of the present invention, a polyurethane sponge (AS ONE, SE-EMT-1) and an ICG aqueous solution (7.5x10 -5 M) were used to manufacture a fluorescent fiber body. Reference Example 38 was manufactured by the manufacturing method of only the compound adhesion step (A) of the method for manufacturing the fluorescent fiber body of the present invention. Example 83 was manufactured according to Embodiment 1 of the method for manufacturing the fluorescent fiber body of the present invention, and Example 84 was manufactured according to Embodiment 2. As shown in Fig. 24, the fluorescent fiber bodies of Examples 83 to 84 emitted fluorescence in the long wavelength region centered around 910 nm by excitation with near-infrared light (irradiation light) centered at 730 nm. As shown in Fig. 24, fluorescence emission was observed at 800 to 960 nm, but the emission intensity of Example 83 manufactured according to Embodiment 1 was slightly stronger. Since the peak wavelengths are all around 900 nm, the formation of strong aggregates is presumed. Since polyurethane has polar urethane bonds with high affinity for ICG in its repeating units, it is expected that higher luminescence intensity can be obtained by dyeing at a lower solution concentration.

[0089] 《Example 85》 In this example, according to Embodiment 2 of the method for manufacturing the fluorescent fibrous body of the present invention, a cotton non-woven gauze (white cross, freeze) and an ICG aqueous solution (1.5x10 -4 M) were used to produce a fluorescent fibrous body. Except for using a cotton non-woven fabric as the fibrous body, the steps of (preparation, dyeing + steaming treatment, washing to drying) were the same as those in Example 13. As shown in Fig. 25, the fluorescent fibrous body of Example 85 emitted fluorescence in the long wavelength region centered at 829 nm by excitation with near-infrared light (irradiation light) centered at 730 nm. Compared with Example 13 using cotton gauze, the emission wavelength was almost the same, and the emission intensity was slightly lower, but it had sufficient luminescence performance as a fluorescent fibrous body.

[0090] 《Examples 86 - 87》 In this example, according to Embodiment 2 of the method for manufacturing the fluorescent fibrous body of the present invention, a medical transparent polyurethane tube (Bio Research Center Co., Ltd., Micro-Renathane, MRE160 50FT) and an ICG aqueous solution (1.5x10 -4 M) were used to produce fluorescent fibrous bodies at different steaming treatment temperatures (121 °C, 132 °C). The steps of (preparation, dyeing + steaming treatment, washing to drying) were the same as those in Embodiment 2 (Example 37 and Example 13), but since the outer diameter of the transparent tube was 4 mm and the wall thickness was 0.875 mm, which was thick, the steaming treatment time was extended to 90 minutes. As shown in Fig. 25, the fluorescent fiber bodies of Example 86 and Example 87 emitted fluorescence in the long wavelength range centered at 824 nm when excited by near-infrared light (irradiation light) centered at 730 nm. Compared with Example 84 using a polyurethane sponge, the emission wavelength was significantly shortened, indicating that the formation of aggregates was suppressed, and the transparent polyurethane tube also had sufficient luminescence performance as a fluorescent fiber body. The relatively low luminescence intensity is because the transparent tube functions as an optical fiber, so the fluorescence emission from ICG is confined and propagated inside the tube, making it difficult to escape to the outside. Currently, transparent polyurethane tubes are used as gastric tubes, bile duct catheters, and urinary catheters for surgical operations. By their fluorescence emission, their presence can be clearly known from the outside, and they can also be used as fluorescent labels (markers).

[0091] 《Examples 88 - 89》 In this example, according to Embodiment 2 of the method for manufacturing the fluorescent fiber body of the present invention, a fluorescent fiber body was manufactured using cotton gauze and an ICG aqueous solution (7.5x10 -5 M). Here, in Example 88, the dyed cotton gauze was immersed in another glass bottle filled with distilled water and shaken at 40 °C for 5 minutes for washing. The same operation was repeated 5 times after changing the distilled water. In Example 89, the dyed cotton gauze was immersed in another glass bottle filled with physiological saline (0.9 w / v% saline solution) and shaken at 40 °C for 5 minutes for washing. The same operation was repeated 4 times after changing the physiological saline, and then it was immersed in another glass bottle filled with distilled water and shaken at 40 °C for 5 minutes for 1 wash. As shown in Fig. 26, the fluorescent fiber bodies of Examples 88 and 89 emitted fluorescence centered around 830 nm when excited by near-infrared light (irradiation light) centered at 730 nm. As shown in Fig. 26 (1C, 2C), fluorescence coloring was observed at 800 - 960 nm, but the luminescence intensity of Example 89 washed with physiological saline was slightly higher.

[0092] Table 1 summarizes the fiber bodies, embodiments, and luminescence intensities of each example. In any of the examples, since fluorescence emission of near-infrared light with a long wavelength of about 800 to 880 nm was confirmed in the fluorescent fiber body, it can be determined that ICG or an ICG derivative is bound to the fiber body.

[0093]

Table 1-1

[0094]

Table 1-2

[0095]

Table 1-3

[0096]

Table 1-4

[0097] 《Usage Example 1》 Figure 27 is a photograph obtained by detecting cotton gauze (Examples 10 to 15) manufactured in Embodiment 2 using an aqueous solution with different ICG concentrations in a fluorescence green mode, a fluorescence blue / orange mode, or a fluorescence monochrome mode using a fluorescence imaging system (FIS, STRYKER, SPY-PHI system). As shown in Figure 28, all cotton gauzes are projected in bright green and have sufficient emission intensity while passing through the large intestine.

[0098] 《Usage Example 2》 In this usage example, the ICG-stained cotton gauze manufactured in Example 24 is directly observed without passing through a display using a MIPS surgical support device (Mitaka Kohki). As shown in Figure 29, since the fluorescence wavelength of ICG is near-infrared light centered around 830 nm, it cannot be visually recognized with the naked eye. However, by applying projection mapping technology, it is projected in bright blue and has sufficient visual recognition sensitivity by visual inspection.

[0099] 《Usage Example 3》 In this usage example, it is a photograph in which the ICG-stained cotton gauze produced in Example 24 was used in an actual digestive system surgery, and the cotton gauze fluorescent fiber body was detected in the fluorescent green mode (Figure 30). The explanations of individual photographs are as follows. a. The state before placing the ICG fluorescent gauze on the dorsal side of the lesser omentum of the stomach. b. After placing the ICG fluorescent gauze on the dorsal side of the lesser omentum of the stomach. The gauze cannot be identified under white light. c. The state in which the ICG fluorescence from the gauze is permeating the lesser omentum of the stomach. d. Identifying the ICG fluorescent gauze under white light. e. Before placing the ICG fluorescent gauze under the submesocolon of the colon. f. The state in which the ICG fluorescence from the gauze is permeating the mesocolon. The gauze cannot be identified under white light. g. Peeling the mesocolon from the retroperitoneum relying on fluorescence and identifying the ICG fluorescent gauze under white light. h. Identifying the ICG fluorescent gauze under white light. i. Assuming intraoperative loss of the gauze, the state before placing the ICG fluorescent gauze on the dorsal side of the mesentery of the small intestine. j. ICG fluorescence from the gauze. k. After placing the ICG fluorescent gauze on the dorsal side of the mesentery of the small intestine. The gauze cannot be identified under white light. l. The state in which the ICG fluorescence from the gauze is permeating the mesentery of the small intestine. It is shown that it can prevent the loss of the gauze. m. Assuming intraoperative loss of the gauze, placing the ICG fluorescent gauze on the dorsal side of the spleen. It cannot be identified under white light. n. The ICG fluorescent gauze placed on the dorsal side of the spleen can be identified under near-infrared light. o. The state after peeling the mesocolon from the retroperitoneum relying on ICG fluorescence. p. After removing the gauze, it can be confirmed that there is no ICG fluorescence from the tissue and no leakage from the gauze is observed.

[0100] 《Reference Example 39 and Examples 90 to 91》 In this reference example and examples, a fluorescent fiber body was produced by the production method of only the compound adhesion step (A) and according to Embodiments 1 to 2 of the production method of the fluorescent fiber body of the present invention, using a silk fabric and an ICG aqueous solution (7.5x10 -5 M). Except for using a silk fabric (habutae, Shikisya Co., Ltd.) and setting the concentration of the ICG aqueous solution to 7.5x10 -5 M, the operations according to Reference Examples 1 to 3, Examples 1 to 2, or Examples 8 to 9 were repeated to obtain a fluorescent fiber body. As shown in Figure 31, fluorescence coloring was observed at 800 to 960 nm.

Industrial Applicability

[0101] The fluorescent fiber body of the present invention can be effectively used in surgical operations using a fluorescence imaging system (FIS), can simply and with a high probability prevent the remaining accidents such as gauze, and by using these fiber bodies as gauze, sponges, and various medical instruments, they can be temporarily inserted and retained in a patient's body for use, and can be used as a fluorescent-emitting label (marker) for obtaining anatomical position information for smoothly performing the operation and accurately guiding (guiding) the progress direction of the operation.

Claims

1. The following formula (1): 【Chemistry 1】 (In the formula, R １ Each independently represents -(CH ２ ) n-R ３ and R ２ is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a carboxyl group, a sulfonic acid group, or an amide group, R ３ is -SO ３ － or -CO-R ４ and R ４ is an oxygen atom, -O-(CH ２ ) m-R ５ , or -NH-(CH ２ ) m-R ５ m is an integer from 0 to 3; R ５ is a dioxopyrrolidine group, an alkyne group having 3 to 5 carbon atoms, an amino group, or an azide group (-N ３ ) and R １ Any one of the following is -(CH ２ ) n-SO ３ － and n is an integer from 3 to 10. or a salt thereof is bound to a fiber of a fiber material selected from the group consisting of cellulose-based fibers, polyurethane fibers, animal hair fibers, silk fibers, acetate-based fibers, and aliphatic polyamide fibers, (1) The compound was applied to the fiber body in a solution state, and then the fiber body was subjected to a steam treatment, (2) The compound was applied to the fiber in a solution state while being steamed, or (3) The compound is applied to a fibrous body in a solution state and then subjected to a steaming treatment, and then further subjected to a steaming treatment. Fluorescent fiber body.

2. The fluorescent fiber body of claim 1 , which is for use in a surgical procedure using a fluorescent imaging system.

3. (A) The following formula (1): 【Chemistry 2】 (In the formula, R １ Each independently represents -(CH ２ ) n-R ３ and R ２ is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a carboxyl group, a sulfonic acid group, or an amide group, R ３ is -SO ３ － or -CO-R ４ and R ４ is an oxygen atom, -O-(CH ２ ) m-R ５ , or -NH-(CH ２ ) m-R ５ m is an integer from 0 to 3; R ５ is a dioxopyrrolidine group, an alkyne group having 3 to 5 carbon atoms, an amino group, or an azide group (-N ３ ) and R １ Any one of the following is -(CH ２ ) n-SO ３ － and n is an integer from 3 to 10. or a salt thereof in a solution state to a fiber material selected from the group consisting of a cellulose-based fiber material, a polyurethane fiber material, an animal hair fiber material, a silk fiber material, an acetate-based fiber material, and an aliphatic polyamide fiber material; and (B) A method for producing a fluorescent fiber body, comprising a step of subjecting the fiber body to which the compound is attached to a steam treatment (high-temperature, high-pressure steam treatment).

4. The method for producing a fluorescent fiber body according to claim 3 , wherein the steps (A) and (B) are carried out in that order, or the steps (A) and (B) are carried out together.

5. The method for producing a fluorescent fiber body according to claim 4, further comprising a step (B2) of subjecting the fiber body to a steaming treatment (high-temperature, high-pressure steam treatment) after carrying out the steps (A) and (B) together.

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