JP2014136116A - Ureteral catheter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a ureteral catheter capable of preventing a wound of a ureter caused by damage in peeling on the ureter.SOLUTION: A ureteral catheter 1 includes one or more luminal lumens including near infrared fluorescent pigment which emits near infrared fluorescent when emitting near infrared ray of wavelength of 500 nm to 1400 nm. The ureteral catheter 1 allows check of an extending state with a monitor 21 by irradiating from a light source 18 near infrared ray 17 with a specific wavelength having excellent transmissive characteristics for a biological body, and then receiving by a camera 19 near infrared fluorescent emitted from the near infrared fluorescent pigment.

Description

  The present invention relates to a ureteral catheter.

  A ureter stenosis / adhesion due to a tumor around the ureter, or a female genital uterine fibroid or endometriosis. In this case, it is necessary to perform treatment to dilate and peel the ureter at an early stage. Moreover, the ureter may meander. The meandering of the ureter itself is unlikely to cause direct physiological problems other than dysphagia. However, for example, when undergoing transurethral ureteric lithotripsy during urinary calculus treatment, if the ureter is meandering, it is difficult to insert the catheter into the ureter, which may damage the ureteral mucosa. . For this reason, the treatment which corrects a ureter is performed.

  A ureteral catheter has been developed for such treatment (Patent Document 1).

Japanese Patent Application Laid-Open No. 64-80367

  However, normally, in such a treatment with a ureteral catheter, there is a risk that the ureter is damaged due to injury at the time of ureteral detachment, and the abdominal cavity is contaminated.

  Therefore, the present invention has been made in view of the above circumstances, and an object thereof is to provide a ureteral catheter that can reduce damage to the ureter due to injury during ureteral detachment.

  As a result of intensive studies to solve the above problems, the present inventors have found that the above problems can be solved by using a near-infrared fluorescent dye that emits near-infrared fluorescence when irradiated with near-infrared light of a specific wavelength in a ureteral catheter. The inventors have found that this can be solved and completed the present invention.

  That is, the above object can be achieved by a ureteral catheter having one or more lumen lumens containing a near-infrared fluorescent dye that emits near-infrared fluorescence when irradiated with near-infrared light having a wavelength of 500 nm to 1400 nm.

  According to the present invention, the ureteral catheter can be visually recognized safely.

It is a schematic sectional drawing which shows the ureteral catheter of 1st Embodiment of this invention. It is a schematic sectional drawing which shows the ureteral catheter of 2nd Embodiment of this invention. It is a figure explaining one Embodiment of the technique for indwelling in a ureter using the ureteral catheter of 1st Embodiment of this invention. It is a figure explaining one Embodiment of the technique for indwelling in a ureter using the ureteral catheter of 1st Embodiment of this invention. It is a figure explaining one Embodiment of the technique for indwelling in a ureter using the ureteral catheter of 1st Embodiment of this invention. It is a figure explaining further other embodiment of the procedure for indwelling in a ureter using the ureteral catheter of a 2nd embodiment of the present invention.

  The present invention relates to a ureteral catheter having one or more lumen lumens containing a near-infrared fluorescent dye that emits near-infrared fluorescence when irradiated with near-infrared light having a wavelength of 500 nm to 1400 nm. The present invention includes a near-infrared fluorescent dye that emits near-infrared fluorescence when irradiated with near-infrared light having a specific wavelength. The measurement method using light has an advantage that a ureteral catheter can be visually recognized by irradiating light having a selected wavelength. Moreover, since near-infrared light excellent in the permeability of the living body is used as the irradiated light, the ureteral catheter introduced into the living body can be confirmed noninvasively and well. .

  Conventionally, the ureter has traveled through the connective tissue, and identification is very difficult by normal visual observation. In addition, as a means for visualizing the ureter, a method of inserting a normal ureteral catheter has also been implemented. According to this means, the visualization and tactile sensation of the ureter is enhanced, but it is still difficult to confirm the ureter running particularly in a place where there is fibrosis or scarring of the retroperitoneum due to tumor adhesion or endometriosis. For this reason, damage to the ureter caused by the ureteral catheter cannot be completely prevented, and urine leaks into the abdominal cavity, resulting in a problem that patient QOL is lowered due to problems such as infection and inflammation. In contrast, when the ureteral catheter of the present invention is used, the introduction of a ureteral catheter that emits near-infrared fluorescence even after the ureter is constricted or adhered due to tumor, uterine fibroids, endometriosis, etc. Since the travel of the ureter can be clearly visualized along the route, it is possible to correct the meandering and narrowing of the ureter and to expand and peel the ureter. For this reason, it is possible to suppress and prevent damage to the ureter due to injury at the time of ureteral detachment, and avoid contamination in the abdominal cavity. Furthermore, when the ureteral catheter of the present invention has a balloon, there is an advantage that the ureter can be peeled reliably by clarifying the ureter by expanding the balloon in the meandering portion and the narrowed portion. is there.

  Furthermore, it is also assumed that a luminescent catheter is used as a ureteral catheter and visualized. Since the luminescent catheter has an optical fiber inside, urine excretion is performed between the ureter and the outer wall of the ureter catheter. For this reason, urinary excretion becomes difficult at the adhesion part or the like. Furthermore, it is necessary to prepare a device body that generates heat or emits light with an optical fiber for a long time. On the other hand, according to the urinary catheter of the present invention, near-infrared fluorescence emitted by the near-infrared fluorescent dye does not generate heat even after a long time, and the device itself is simple.

  Embodiments of the present invention will be described below. In addition, this invention is not limited only to the following embodiment. In addition, the dimensional ratios in the drawings are exaggerated for convenience of explanation, and may be different from the actual ratios.

  In the present specification, “X to Y” indicating a range means “X or more and Y or less”, and “weight” and “mass”, “wt%” and “mass%”, “part by weight” and “ “Part by mass” is treated as a synonym. Unless otherwise specified, measurement of operation and physical properties is performed under conditions of room temperature (20 to 25 ° C.) / Relative humidity 40 to 50%.

  The ureteral catheter of the present invention can have the same structure as a normal ureteral catheter. Specifically, as shown in FIG. 1, the ureteral catheter 1 includes a ureteral catheter body 5, a lumen lumen 3 formed inside the ureteral catheter body 5, and a distal part of the ureteral catheter body 5. At least one urination hole 2 formed on the distal end (front end) side, and a connection body 4 installed on the proximal end (base end) side of the ureteral catheter body 5 are provided. Here, the lumen lumen 3 communicates with the urination hole 2 for the purpose of excretion of urine. When the ureteral catheter is introduced into the ureter, the urine passes through the lumen lumen 3 via the urinary hole 2 and is discharged (excreted) outside the body via the connection body 4 installed at the tip of the lumen lumen 3. Is done. In this way, the urination hole and lumen lumen allow urine to be excreted through the lumen lumen even under prolonged indwelling, thus preventing a transient increase in urinary pressure in the renal pelvis and obstruction Nephritis and even hydronephrosis can be avoided. In addition, at least one urination hole 2 may be formed on the distal end (tip) side of the ureteral catheter body 5; Preferably it is formed. In the present invention, the urination hole 2 does not need to be formed in the ureteral catheter 1. For example, when the distal end (tip) of the urinary catheter 1 is open, such a urination hole is not formed. Even if not, it passes through the lumen lumen 3 through this opening, and is discharged (excreted) out of the body via the connection body 4 installed at the tip of the lumen lumen 3.

  In FIG. 1, only one lumen lumen 3 is formed in the ureteral catheter body 5, but the number of lumen lumens is not limited to one. For example, the ureteral catheter of the present invention may be provided with a balloon 6 at the tip of the ureteral catheter body 5 as shown in FIG. That is, the urinary catheter may further have a balloon. By further installing the balloon in this manner, the ureteral catheter can be more firmly fixed in the ureter, and the movement of the ureteral catheter due to the movement of the patient's body can be suppressed / prevented. For this reason, urine can be efficiently excreted outside the body for a long period of time. Furthermore, by expanding the balloon, the movement of the ureteral catheter of the present invention and the actual ureteral adhesion can be corrected, and the ureter can be safely peeled off by visualization clearly from the surrounding tissue. In this case, a lumen lumen (not shown) different from the lumen lumen 3 for excretion of urine is provided for the purpose of expanding the balloon. A balloon joint 7 is provided at the tip of the lumen lumen, and the balloon 6 is expanded and contracted by introducing and discharging gas or liquid through the balloon joint 7. Further, in addition to the lumen lumen for balloon expansion / contraction, a lumen lumen for drug injection, a lumen lumen for forcing the ureteral meander (for example, as described in JP-A-64-80367) A lumen lumen for inserting a shape memory alloy wire) and a lumen lumen for contrast medium administration may be provided separately. Here, the number of lumen lumens provided in the ureteral catheter is not particularly limited as long as it is 1 or more, and is appropriately selected depending on the catheter diameter and treatment content. The number of lumen lumens provided in the ureteral catheter is preferably 1 to 3.

  The urinary catheter of the present invention includes a near-infrared fluorescent dye that emits near-infrared fluorescence when irradiated with near-infrared light having a wavelength of 500 nm to 1400 nm. Here, the arrangement form of the near-infrared fluorescent dye on the urinary catheter is not particularly limited. For example, (a) a form to be introduced (included) in or in part of the urinary catheter, (b) ureter Any form such as covering (applying) part or all of the catheter surface may be used. That is, in the ureteral catheter of the present invention, at least a part of the urinary catheter is formed of a material containing a near-infrared fluorescent dye, or at least a part of the surface of the catheter or lumen lumen contains a near-infrared fluorescent dye. It can be coated with a material.

  In the above embodiment (a), the entire urinary catheter of the present invention may contain a near infrared fluorescent dye, or a part of the catheter may contain a near infrared fluorescent dye. In the latter case, In view of the visual recognition effect of the catheter, it is preferable that a near-infrared fluorescent dye is contained in the catheter tip, particularly in the catheter tip where the urination hole is installed. Similarly, in the above-described embodiment (b), the surface of the ureteral catheter of the present invention may be coated (applied) with a near-infrared fluorescent dye, or a portion of the catheter surface may be coated with a near-infrared fluorescent dye ( In the latter case, in consideration of the visual recognition effect of the catheter, the near-infrared fluorescent dye is coated on the surface of the distal end of the catheter, particularly on the surface near the distal end of the catheter where the urination hole is installed. (Applying) is preferable. In addition, the near-infrared fluorescent dye may be disposed (applied) on either the surface of the ureteral catheter (outer surface) or the surface of its lumen lumen, but considering the visibility during near-infrared irradiation, It is preferable to arrange (apply) a near infrared fluorescent dye on the surface (outer surface) of the urinary catheter, that is, at least a part of the surface (outer surface) of the urinary catheter is made of a material containing a near infrared fluorescent dye. Preferably it is coated. In consideration of safety, it is preferable to arrange (apply) a near-infrared fluorescent dye on the lumen lumen, that is, at least a part of the surface of the lumen lumen is coated with a material containing the near-infrared fluorescent dye. It is preferred that

  In the present invention, a near-infrared fluorescent dye that emits near-infrared fluorescence when irradiated with near-infrared light having a wavelength of 500 nm to 1400 nm (hereinafter also simply referred to as “near-infrared fluorescent dye”) Although it does not restrict | limit especially if it emits external fluorescence, It is preferable that it is a near-infrared fluorescent pigment | dye which emits near-infrared fluorescence at the time of near-infrared irradiation of wavelength 500nm-1400nm, and near-red at the time of near-infrared irradiation of wavelength 600nm-1400nm A near-infrared fluorescent dye that emits external fluorescence is preferred. As such a near-infrared fluorescent dye, for example, the following formula (1) described in JP-A No. 2011-162445:

And an azo-boron complex compound represented by the following formula (2):

And indocyanine green, patent blue, indigo carmine and the like.

  In the above formula (1), X represents an unsubstituted or substituted aryl group or an unsubstituted or substituted heteroaryl group.

  Here, “unsubstituted aryl group” means an aromatic hydrocarbon group. The unsubstituted aryl group is not particularly limited, but may be an aryl group having 6 to 30 carbon atoms. More specifically, non-condensed hydrocarbon groups such as phenyl group, biphenyl group, terphenyl group; pentarenyl group, indenyl group, naphthyl group, azulenyl group, heptaenyl group, biphenylenyl group, fluorenyl group, acenaphthylenyl group, preadenenyl group , Condensed polycyclic hydrocarbon groups such as acenaphthenyl group, phenalenyl group, phenanthryl group, anthryl group, fluoranthenyl group, acephenanthrenyl group, aceantrirenyl group, triphenylenyl group, pyrenyl group, chrysenyl group, naphthacenyl group, etc. Can be mentioned. Among these, an aryl group having 6 to 10 carbon atoms is preferable, and a phenyl group is more preferable.

  The “unsubstituted heteroaryl group” means an aromatic heterocyclyl group having a 5-membered ring, 6-membered ring or condensed ring having at least one heteroatom such as a nitrogen atom, an oxygen atom or a sulfur atom. Although it does not restrict | limit especially as an unsubstituted heteroaryl group, A C1-C20 heteroaryl group may be sufficient. More specifically, pyridyl group, pyrimidyl group, pyridinyl group, pyrimidinyl group, pyrazinyl group, triazinyl group, furanyl group, pyrrolyl group, thiophenyl group (thienyl group), quinolyl group, quinolinyl group, quinolidinyl group, furyl group, piperidyl Group, coumarinyl group, chromenyl group, silafluorenyl group, benzofuranyl group, isobenzofuranyl group, benzimidazolyl group, benzoxazolyl group, benzthiazolyl group, dibenzofuranyl group, benzothiophenyl group, dibenzothiophenyl group, indolyl group , Isoindolyl group, carbazolyl group, pyrazolyl group, imidazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, indazolyl group, benzothiazolyl group, pyridazinyl group, cinnolyl group, quinazolyl group, quinoxalyl group, Razinyl group, phthalazine dionyl group, phthalamidyl group, chromonyl group, naphtholactamyl group, quinolonyl group, naphthalidinyl group, benzimidazolonyl group, benzoxazolonyl group, benzothiazolonyl group, benzothiazothionyl group, Quinazolonyl group, quinoxalonyl group, phthalazonyl group, dioxopyrimidinyl group, pyridonyl group, isoquinolonyl group, isoquinolinyl group, isothiazolyl group, thiadiazole group, benzisoxazolyl group, benzisothiazolyl group, indazironyl group, acridinyl group, acridonyl group Quinazoline dionyl group, quinoxaline dionyl group, benzoxazine dionyl group, benzoxazinonyl group, naphthalimidyl group, dithienocyclopentadienyl group, dithienosilacyclopentadienyl group, dithieno Roriru group, benzodithiolium phenyl group. Of these, a heteroaryl group containing a nitrogen atom is preferred, and a benzothiazolyl group is more preferred.

In addition, the substituent in the case where the aryl group or heteroaryl group has a substituent is not particularly limited, and examples thereof include a nitro group (—NO ₂ ), a cyano group (—CN), and an alkoxy having 2 to 13 carbon atoms. A carbonyl group, an alkyl group having 1 to 12 carbon atoms, a mono (alkyl) amino group of the formula: —NH (R ⁹ ) (wherein R ⁹ represents an alkyl group having 1 to 12 carbon atoms), a formula : -N (R ⁹ ) ₂ (wherein R ⁹ independently represents an alkyl group having 1 to 12 carbon atoms), a di (alkyl) amino group, a carboxyl group (—COOH), a hydroxyl group ( -OH) or an alkoxy group having 1 to 12 carbon atoms.

  Here, as the alkoxycarbonyl group having 2 to 13 carbon atoms, methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, n-butoxycarbonyl group, sec-butoxycarbonyl group, tert-butoxycarbonyl group N-pentoxycarbonyl group, isopentoxycarbonyl group, neopentoxycarbonyl group, n-hexyloxycarbonyl group, n-heptyloxycarbonyl group, n-octyloxycarbonyl group, n-nonyloxycarbonyl group, n- Examples include linear or branched alkoxycarbonyl groups such as a decyloxycarbonyl group, an n-undecyloxycarbonyl group, an n-dodecyloxycarbonyl group, and a 2-ethylhexyloxycarbonyl group. Of these, a linear or branched alkoxycarbonyl group having 2 to 13 carbon atoms is preferred.

Moreover, a C1-C12 alkyl group is a linear, branched or cyclic alkyl group. Although there is no restriction | limiting in particular as a C1-C12 alkyl group, For example, a methyl group, an ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl Group, n-pentyl group, isopentyl group, tert-pentyl group, neopentyl group, 1,2-dimethylpropyl group, n-hexyl group, isohexyl group, 1,3-dimethylbutyl group, 1-isopropylpropyl group, 1, 2-dimethylbutyl group, n-heptyl group, 1,4-dimethylpentyl group, 3-ethylpentyl group, 2-methyl-1-isopropylpropyl group, 1-ethyl-3-methylbutyl group, n-octyl group, 2 -Ethylhexyl group, 3-methyl-1-isopropylbutyl group, 2-methyl-1-isopropyl group, 1-t-butyl-2-methyl Lopyl group, n-nonyl group, 3,5,5-trimethylhexyl group, n-decyl group, isodecyl group, n-undecyl group, 1-methyldecyl group, n-dodecyl group, cyclopropyl group, cyclopentyl group, cyclohexyl group , Norbornyl group, adamantyl group and the like. Of these, a linear or branched alkyl group having 1 to 10 carbon atoms is preferable. In particular, as R ⁶ and R ⁷ , an alkyl group having 2 to 12 carbon atoms is preferable, an alkyl group having 2 to 10 carbon atoms is more preferable, and a linear alkyl group having 2 to 8 carbon atoms is particularly preferable. In other cases, an alkyl group having 1 to 6 carbon atoms is preferable, an alkyl group having 1 to 4 carbon atoms is more preferable, a methyl group and an ethyl group are still more preferable, and a methyl group is particularly preferable.

In the mono (alkyl) amino group of the formula: —NH (R ⁹ ) and the di (alkyl) amino group of the formula: —N (R ⁹ ) ₂ , R ⁹ represents an alkyl group having 1 to 12 carbon atoms. Here, since the alkyl group having 1 to 12 carbon atoms has the same definition as the above alkyl group, the description is omitted here. In the di (alkyl) amino group of the formula: —N (R ⁹ ) ₂ , two R ^{9 s} may be the same or different from each other. More specifically, mono (alkyl) amino groups include methylamino group, ethylamino group, propylamino group, isopropylamino group, n-butylamino group, sec-butylamino group, tert-butylamino group, pentyl. An amino group, a hexylamino group, etc. are mentioned. Among these, preferably R ⁹ is mono- (alkyl) amino group represents an alkyl group having 1 to 6 carbon atoms, R ⁹ is more preferably mono (alkyl) amino group represents an alkyl group having 1 to 4 carbon atoms A methylamino group and an ethylamino group are particularly preferred. Di (alkyl) amino groups include dimethylamino group, diethylamino group, dipropylamino group, diisopropylamino group, dibutylamino group, diisobutylamino group, di-sec-butylamino group, di-tert-butylamino group, dipentyl Examples include amino group, dihexylamino group, ethylmethylamino group, methylpropylamino group, butylmethylamino group, ethylpropylamino group, butylethylamino group and the like. Among these, preferably R ⁹ is di (alkyl) amino group represents an alkyl group having 1 to 6 carbon atoms, R ⁹ is more preferably di (alkyl) amino group represents an alkyl group having 1 to 4 carbon atoms And particularly preferred is a di (alkyl) amino group in which R ⁹ represents a methyl group or an ethyl group.

  A C1-C12 alkoxy group is a linear or branched alkoxy group. The alkoxy group having 1 to 12 carbon atoms is not particularly limited. For example, methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, pentyloxy group, hexyloxy group, 2-ethylhexyloxy group, Examples include octyloxy group, nonyloxy group, decyloxy group, undecyloxy group, dodecyloxy group and the like. Among these, an alkoxy group having 1 to 6 carbon atoms is preferable, an alkoxy group having 1 to 4 carbon atoms is more preferable, a methoxy group and an ethoxy group are still more preferable, and a methoxy group is particularly preferable.

In the above formula (1), R ¹ represents an alkyl group having 1 to 12 carbon atoms, an aryl group, an arylethenyl group, an arylethynyl group, an alkoxy group having 1 to 12 carbon atoms, an aryloxy group, or a halogen atom. Represent. Here, the two R ^{1 s} may be the same or different. Alternatively, in the above formula (1), one R ¹ represents —O—C (═O) — and is bonded to X to form a six-membered ring, and the other R ¹ represents carbon It may represent an alkyl group having 1 to 12 atoms, an aryl group, an arylethenyl group, an arylethynyl group, an alkoxy group having 1 to 12 carbon atoms, an aryloxy group, or a halogen atom. Here, the alkyl group having 1 to 12 carbon atoms, the aryl group, and the alkoxy group having 1 to 12 carbon atoms are the same as defined in the substituent “X”, and thus the description thereof is omitted here. In the above formula (1), when two R ¹ are alkoxy groups, the hydrocarbon groups may be bonded together to form a cyclic structure together with the boron atom.

  The arylethenyl group has the following formula:

A group represented by the following formula:

It is preferable that it is group shown by these. Here, the arylethenyl group may be a trans type or a cis type, but a trans type is preferable from the viewpoint of stability. In the above formula, Ar represents an aryl group, which is the same as the definition in the substituent “X”, and thus the description thereof is omitted here. The arylethynyl group has the following formula:

Here, Ar represents an aryl group, and is the same as the definition in the substituent “X”, and thus the description thereof is omitted here. The aryloxy group is not particularly limited, but may be an aryloxy group having 6 to 30 carbon atoms. More specifically, a phenoxy group, 2-naphthyloxy group, anthracenoxy group, o, m, p-cyclohexyl-phenoxy group and the like can be mentioned. Moreover, as a halogen atom, a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom are mentioned. Among these, a fluorine atom, a chlorine atom, and a bromine atom are preferable, and a fluorine atom is more preferable.

In the above formula (1), R ² and R ³ are connected to each other to —O—, —S—, or —N (R ⁸ ) — (where R ⁸ is a hydrogen atom or a carbon atom number of 1 to R ⁴ and R ⁵ represent a hydrogen atom, or R ⁴ and R ⁵ are connected to each other to represent —O—, —S— or —N (R ⁸ )-(Wherein R ⁸ represents a hydrogen atom or an alkyl group having 1 to 12 carbon atoms), and R ² and R ³ represent a hydrogen atom. Here, since the alkyl group having 1 to 12 carbon atoms is the same as the definition in the substituent “X”, the description is omitted here.

In the above formula (1), R ⁶ and R ⁷ are a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an unsubstituted or substituted aryl group, or an unsubstituted or substituted heteroaryl group. Represents. Here, R ⁶ and R ⁷ may be the same or different. In addition, the alkyl group having 1 to 12 carbon atoms, the unsubstituted or substituted aryl group, and the unsubstituted or substituted heteroaryl group are the same as defined in the substituent “X”. The description is omitted here.

Of the azo-boron complex compounds of the above formula (1), one R ¹ represents —O—C (═O) — and is bonded to X to form a 6-membered ring, and the other R ¹ represents an alkyl group having 1 to 12 carbon atoms, an aryl group, an arylethenyl group, an arylethynyl group, an alkoxy group having 1 to 12 carbon atoms, an aryloxy group, or a halogen atom represented by the following formula (3). Azo-boron complex compounds and azo-boron complex compounds of the following formulas (4) and (5) are preferred. That is, the near-infrared fluorescent dye preferably contains an azo-boron complex compound represented by any of the following formulas (3) to (5).

However, in said formula, X and R < ¹ > -R < ⁷ > are the definitions similar to the said Formula (1),
Specific examples of such an azo-boron complex compound of the formula (1) include the following. In the following, the azo-boron complex compound of formula (1) is defined by the following symbols.

In the above formula (2), X and R ^{2 to} R ⁷ have the same definition as in the above formula (1), and thus the description thereof is omitted here.

  Specific examples of such a hydrazone compound of formula (2) include the following. In the following, the hydrazone compound of the formula (2) is defined by the following symbols.

  The hydrazone compound of the above formula (2) is a tautomer of an azo compound as described below, and the azo compound is equivalent to the hydrazone compound of the formula (2) and is included in the scope of the present invention. It is.

  Among these, considering the emission intensity (easiness of visual recognition), stability, and low deterioration of near infrared fluorescence, the azo-boron complex compound of the above formula (1) and the hydrazone compound of the above formula (2) Is preferred. That is, the near-infrared fluorescent dye preferably contains an azo-boron complex compound of the above formula (1) or a hydrazone compound of the above formula (2). In consideration of the emission intensity of near-infrared fluorescence (ease of visual recognition), durability of light emission (possibility of visual recognition over a long period of time), stability, low degradation, etc., the near-infrared fluorescent dye is expressed by the above formula ( It is preferably an azo-boron complex compound of 1), a hydrazone compound of the above formula (2), or a mixture thereof, and particularly preferably an azo-boron complex compound of the above formula (1). The azo-boron complex compound of the above formula (1) has very strong light absorption characteristics in the visible light region, and also exhibits good light emission properties in the near infrared region. Moreover, since the azo-boron complex compound of the above formula (1) can be easily dispersed in a polymer resin, it can be easily kneaded with the material constituting the catheter. In addition, the azo-boron complex compound of the above formula (1) has advantages such as excellent light resistance and heat resistance. For this reason, the azo-boron complex compound of the said Formula (1) is used as a near-infrared fluorescent pigment | dye excellent in the ureteral catheter of this invention. Moreover, the azo-boron complex compound of the said Formula (1) can be manufactured by a simple method so that it may explain in full detail below.

  The near infrared fluorescent dye may be composed of only one kind of near infrared fluorescent dye or may be in the form of a mixture of two or more kinds. For example, when the near-infrared fluorescent dye is an azo-boron complex compound of the above formula (1), the near-infrared fluorescent dye is composed of only one kind of the azo-boron complex compound of the above formula (1). It may be configured, or may be in the form of a mixture of two or more azo-boron complex compounds of the above formula (1).

The production method of the azo-boron complex compound of the above formula (1) and the hydrazone compound of the above formula (2) is not particularly limited, and can be applied in the same manner or appropriately modified with known methods. For example, a method described in JP2011-162445A is preferably used. That is, the hydrazone compound of the above formula (2) can be produced by the reaction of an orthoquinone derivative represented by the following formula (6) and a hydrazine hydrochloride represented by the following formula (7) as shown in the following reaction formula. . In the following formulas (6) and (7), X and R ^{2 to} R ⁷ have the same definitions as in the above formula (1), and thus the description thereof is omitted here. In the following reaction formula, a hydrazine compound of the formula: X—NH—NH ₂ may be used instead of the hydrazine hydrochloride represented by the following formula (7).

Further, the azo-boron complex compound of the above (1) is obtained by combining the hydrazone compound of the formula (2) thus obtained and the boron compound of the following formula (8) as shown in the following reaction formula. It can be produced by reaction. In the following formula (8), R ⁹ represents an alkyl group having 1 to 12 carbon atoms, an aryl group, an arylethenyl group, an arylethynyl group, an alkoxy group having 1 to 12 carbon atoms, an aryloxy group, or a halogen atom. represent the atoms are eliminated easily group than that or R ¹ the same as R ^1. Here, “alkyl group”, “aryl group”, “aryl ethenyl group”, “aryl ethynyl group”, “alkoxy group having 1 to 12 carbon atoms”, “aryloxy group” and “halogen atom” Is the same definition as in the above formula (1), and the description is omitted here. Further, ^{R 1} X and ^R 1 to R ⁷ and the following formula (8) in the following formulas (2) are the same as defined in the above formula (1), a description thereof will be omitted.

  The urinary catheter of the present invention includes the above-mentioned near-infrared fluorescent dye and a near-infrared fluorescent dye that emits near-infrared fluorescence when irradiated with near-infrared light having a wavelength of 500 nm to 1400 nm. Here, the arrangement form of the near-infrared fluorescent dye on the urinary catheter is not particularly limited. For example, (a) a form to be introduced (included) in or in part of the urinary catheter, (b) ureter Any form such as covering (applying) part or all of the catheter surface may be used. Hereinafter, (a) a form to be introduced (included) in part or all of the ureteral catheter, and (b) a form to be coated (applied) on part or all of the surface of the ureteral catheter will be described in detail. In addition, the following demonstrates preferable embodiment of each form, and this invention is not limited to the following form.

[(A) Form introduced (included) in part or all of ureteral catheter]
A raw material polymer solid or melt is kneaded with a near-infrared fluorescent dye to prepare a polymer composition, and a catheter is manufactured using this polymer composition.

  The polymer to be used is not particularly limited, and a polymer usually used as a material constituting the catheter can be used. Specifically, polyvinyl chloride, polycarbonate, polyethylene terephthalate, polystyrene, polyethylene, polypropylene, polymethylpentene, polyolefin elastomer, polyamide, polyamide elastomer, polyimide, polyester, polyester elastomer, thermoplastic polyurethane, thermosetting polyurethane, polyurethane elastomer , Silicone rubber such as polydimethylsiloxane having a cross-linked portion, polymethyl methacrylate, polyvinylidene fluoride, polyethylene tetrafluoride, polysulfone, polyethersulfone, polyphenylene sulfide, polyacetal, polystyrene, acrylonitrile styrene copolymer, acrylonitrile butadiene styrene copolymer Coalescence, polyvinyl, silicone, tetrafluoroethylene / Hexafluoropropylene copolymer, tetrafluoroethylene / perfluoroalkyl vinyl ether copolymer, polyvinylidene fluoride, polyvinyl fluoride, ethylene / chlorotrifluoroethylene copolymer, ethylene / tetrafluoroethylene copolymer (ETFE), Polytetrafluoroethylene (PTFE), polyvinyl alcohol, poly (ethylene-vinyl alcohol) copolymer, 2-methacryloyloxydecyl phosphorylcholine homopolymer or copolymer, (2-hydroxyethyl methacrylate) -styrene block copolymer, etc. Can be mentioned. Of these, polyvinyl chloride, thermoplastic polyurethane, polysulfone, polyethersulfone, and silicone are preferable from the viewpoints of biocompatibility, durability, and the like. More preferably, thermoplastic polyurethane, polyvinyl chloride, or silicone is used. In addition, the said polymer may be used individually by 1 type, or 2 or more types may be used with the form of a mixture.

  Here, the mixing ratio of the near-infrared fluorescent dye and the polymer is not particularly limited as long as it is a ratio that emits near-infrared fluorescence to a sufficiently visible level when irradiated with near-infrared light having a wavelength of 500 nm to 1400 nm. Specifically, it is preferable that 0.001 to 10.0 parts by weight of the near infrared fluorescent dye is added to 100 parts by weight of the polymer, and 0.01 to 100 parts by weight of the polymer. A ratio of 1.0 part by weight is more preferable. If it is such a ratio, when near-infrared rays having a wavelength of 500 nm to 1400 nm are irradiated, near-infrared fluorescence is emitted to such an extent that it is sufficiently visible, and the strength, flexibility, biocompatibility, and molding of the catheter itself. Sufficient workability can be secured.

  Moreover, you may add an additive to the said raw material polymer further. Here, the additive is not particularly limited as long as it does not harm the living body, and an additive usually used for a catheter can be used. Specifically, pigment, dye, reinforcing agent (glass fiber, carbon fiber, talc, mica, viscosity favorite, potassium titanate fiber, etc.), filler (carbon black, silica, alumina, titanium oxide, metal powder, wood powder) , Rice husks, etc.), heat stabilizers, oxidation degradation inhibitors, ultraviolet absorbers, lubricants, mold release agents, crystal nucleating agents, plasticizers, flame retardants, antistatic agents, foaming agents and the like. In addition, the said additive may be used individually by 1 type, or may be used in the form of a mixture of 2 or more types.

  Here, the addition amount of the additive is not particularly limited as long as the desired effect can be achieved, and the same amount as the normal addition amount can be applied. Specifically, the ratio of the additive is preferably 1 to 30 parts by weight with respect to 100 parts by weight of the polymer, and the ratio of 1 to 20 parts by weight with respect to 100 parts by weight of the polymer. Is more preferable.

  Further, the method for producing the catheter is not particularly limited, and a known method can be applied in the same manner or appropriately modified. Specifically, (a) the material constituting the catheter (polymer), the near-infrared fluorescent dye, and, if necessary, raw materials such as additives, are put into a kneader such as an extruder, melt-kneaded, A method of molding, (a) A method of premixing the above raw materials and then charging, melt-kneading and molding in the same manner as described above, and (c) A method of supplying raw materials into a molding machine and molding while melting and mixing, etc. Is mentioned. Here, the apparatus for kneading the raw materials is not particularly limited as long as each component can be kneaded. For example, batch kneaders such as rollers, kneaders, roll mills, super mixers, Henschel mixers, Shugi mixers, vertical granulators, high speed mixers, fur matrices, ball mills, steel mills, sand mills, vibration mills, attritors, Banbury mixers And an extruder, a rotor type twin-screw kneader, and the like. Among these, an extruder is preferably used. Examples of the extruder include a screw extruder such as a single-screw extruder and a twin-screw extruder, an elastic extruder, a hydrodynamic extruder, a ram-type continuous extruder, a roll-type extruder, a gear-type extruder, and the like. Can be mentioned. Among these, a screw extruder, particularly a twin screw extruder is preferable, and a twin screw extruder having one or more vents (deaeration ports) with good deaeration efficiency is more preferable. In the above (a), the mixer that can be used for the preliminary mixing is not particularly limited, and known mixers such as a Henschel mixer, a tumbler, and a disper can be used.

  Moreover, the temperature at the time of melting (melting temperature) is not particularly limited, but is preferably equal to or higher than the glass transition temperature of the material (polymer) constituting the catheter. Specifically, the melting temperature is more preferably 10 to 300 ° C. Further, the temperature (kneading temperature) at which the raw materials are kneaded is not particularly limited, but is preferably equal to or higher than the glass transition temperature of the material (polymer) constituting the catheter, and the glass of the material (polymer) constituting the catheter. More preferably, it is not lower than the transition temperature and lower than the melting temperature. Specifically, the kneading temperature is more preferably 100 to 250 ° C. When the kneading temperature is in such a range, it is preferable because the material (polymer) constituting the catheter is softened and the load on the kneading apparatus can be reduced. Here, the “melting temperature” refers to the end point temperature of the crystal melting endothermic peak that appears during temperature rise measurement by a differential scanning calorimeter (DSC). The “glass transition temperature” refers to a transition temperature obtained from the thermograph in measurement with a differential scanning calorimeter based on JIS K7121-1987.

  Thereby, a composition in the form of pellets, powders, granules or beads can be obtained.

  Next, the composition obtained above is formed into a ureteral catheter. Here, a shaping | molding method is not restrict | limited in particular, The well-known method for manufacturing a catheter can be applied similarly or suitably modified. Specific examples include extrusion molding, hollow extrusion molding, injection molding, inflation molding, blow molding, extrusion blow molding, injection blow molding, compression molding, press molding, vacuum molding, calendar molding, and foam molding. The molding conditions are not particularly limited, and may be the same as the molding conditions for a general catheter.

[(B) Form in which part or all of urinary catheter surface is coated (applied)]
A near-infrared fluorescent dye is dissolved in a suitable solvent to prepare a dye solution, and this dye solution is coated (applied) on a predetermined portion of the catheter surface or lumen lumen. Here, the film thickness of the coating (coating film) of the near-infrared fluorescent dye on the catheter surface or lumen lumen is not particularly limited, and varies depending on the type of the near-infrared fluorescent dye used. Specifically, considering the emission intensity of the near-infrared fluorescence (easiness of visual recognition), the film thickness of the near-infrared fluorescent dye on the catheter surface or lumen lumen should be 1 μm or more. Is sufficient, preferably 1 mm or less.

  The solvent used is not particularly limited as long as it can dissolve the near-infrared fluorescent dye, and is appropriately selected depending on the type of the near-infrared fluorescent dye used. Specifically, halogen-based organic solvents such as chloroform and dichloromethane; aliphatic hydrocarbons such as butane, pentane and hexane; aromatic hydrocarbons such as benzene, toluene and xylene; esters such as ethyl acetate and butyl acetate; Water-insoluble ketones such as isobutyl ketone; ethers such as tetrahydrofuran (THF), butyl ether and dioxane; aliphatic alcohols such as methanol, ethanol and isopropanol; acetonitrile, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), two Polymerization comprising carbon sulfide, a copolymer of polyvinylpyrrolidone and polyurethane, a polymer comprising acrylamide or an acrylamide derivative, a monomer having N, N-dimethylaminoethyl acrylate, sugar, or phospholipid in the side chain. Or the like maleic acid polymer. These solvents may be used alone or as a mixed solvent in which two or more of these solvents are combined.

  The concentration of the near-infrared fluorescent dye in the dye solution is not particularly limited. Considering the emission intensity of the near-infrared fluorescence (ease of visual recognition), it is preferably 0.001 to 10.0% by weight, more preferably 0.01 to 1.0% by weight. The amount of coating (application) of the near-infrared fluorescent dye on the catheter surface or lumen lumen is not particularly limited, and varies depending on the type of the near-infrared fluorescent dye used, but the near-infrared fluorescent dye catheter The amount of the film on the surface or lumen lumen (coating film) may be an amount that is 1 μm or more and 1 mm or less, and is appropriately determined in consideration of the emission intensity (ease of visual recognition) of near-infrared fluorescence. You can choose. If it is the said range, when irradiating near infrared rays with a wavelength of 500 nm-1400 nm, near infrared fluorescence can be emitted to such an extent that it can fully be visually recognized. In addition, it is preferable in terms of workability (e.g., ease of application) and production efficiency that a desired amount of near-infrared fluorescent dye can be applied in one application, but if necessary, a desired amount of The coating process may be repeated a plurality of times until the near-infrared fluorescent dye can be coated. However, even if it is out of the above range, it can be sufficiently utilized as long as it does not affect the operational effects of the present invention.

  The coating method is not particularly limited, and a known coating method can be used. Specifically, dipping method (dipping method), coating / printing method, spraying method (spray method), spin coating method, mixed solution impregnation sponge coating method, spray device, bar coater, die coater, reverse coater, comma coater And a method of coating (coating) using a coating apparatus such as a gravure coater, spray coater, doctor knife or the like.

  After the application, the near infrared fluorescent dye can be coated (applied) on the surface of the ureteral catheter or the lumen lumen by drying the applied layer. Here, the drying method is not particularly limited, and for example, it can be dried by heating. The drying temperature is not particularly limited as long as the solvent is sufficiently evaporated and the near-infrared fluorescent dye is applied to the catheter surface. For example, the drying temperature is preferably 10 to 250 ° C, more preferably 10 to 100 ° C. Also, the drying time is not particularly limited as long as the solvent is sufficiently evaporated and the near-infrared fluorescent dye is applied to the catheter surface. For example, 5 minutes to 24 hours is more preferable. Although it does not restrict | limit especially as a heating means (apparatus), For example, oven, a dryer, etc. can be utilized. The drying step may be performed under reduced pressure, normal pressure, or increased pressure, but is preferably performed under normal pressure in consideration of the ease of operation.

  In this manner, a coating layer may be further provided after coating (applying) the near-infrared fluorescent dye on a part or all of the surface of the ureteral catheter. By providing the coating layer in this manner, even when the near-infrared fluorescent dye coating film (coating layer) is in contact with the wall of a living body lumen such as a ureter, the near-infrared fluorescent dye coating film (coating Layer peeling (detachment) is difficult or does not occur. Here, the coating layer is not particularly limited, but may be a hydrophilic surface layer described in detail below, or may be formed using a material constituting the catheter.

  In addition, when the ureteral catheter of the present invention has a balloon, the balloon may be installed at a desired position of the catheter thus obtained using a known method. If necessary, the balloon may contain a near infrared fluorescent dye. In this case, after the balloon-forming material is mixed with the near-infrared fluorescent dye in advance, this mixture may be formed into a balloon by a known manufacturing method. Here, the balloon-forming material is not particularly limited, and known materials generally used for the production of balloons can be used in the same manner. For example, polytetramethylene adipamide (nylon 46), polycaprolactam (nylon 6), polyhexamethylene adipamide (nylon 66), polyhexamethylene sebamide (nylon 610), polyhexamethylene dodecamide (nylon 612) ), Homopolymers such as polyundecanolactam (nylon 11), polydodecanolactam (nylon 12), caprolactam / lauryl lactam copolymer (nylon 6/12), caprolactam / aminoundecanoic acid copolymer (nylon 6) / 11), caprolactam / ω-aminononanoic acid copolymer (nylon 6/9), caprolactam / hexamethylene diammonium adipate copolymer (nylon 6/66), a copolymer of adipic acid and metaxylenediamine, or Hexamethylenediamy Polyamide resins such as copolymers such as copolymers of m and p-phthalic acid, polyethylene resins such as linear low density polyethylene (LLDPE), low density polyethylene (LDPE), high density polyethylene (HDPE) Polyolefins such as polypropylene resins, polyolefins such as ethylene-propylene copolymers, ethylene-vinyl acetate copolymers, and cross-linked products and partially cross-linked products thereof (for example, cross-linked ethylene-vinyl acetate copolymers), epoxy Resin, urethane resin, diallyl phthalate resin (allyl resin), polycarbonate resin, fluorine resin, amino resin (urea resin, melamine resin, benzoguanamine resin), polyester resin (for example, polyethylene terephthalate), styrene resin, acrylic resin, polyacetal resin, Hard segments include vinyl acetate resin, phenol resin, vinyl chloride resin, silicone resin (silicon resin), polyarylene sulfide (eg, polyphenylene sulfide), silicone rubber, latex rubber, nylon 6, nylon 66, nylon 11, nylon 12 and the like And nylon elastomer which is a block copolymer having a soft segment of polyalkylene glycol, polyether, or aliphatic polyester. These may be used individually by 1 type and may use 2 or more types together. In the latter case, the balloon may be in the form of a single layer formed from a mixture of two or more kinds, or in the form of a laminate of two or more kinds of mixtures. Alternatively, as the balloon forming material, a synthetic product or a commercially available product may be used. For example, examples of commercially available polyamide resins include RILSAN (registered trademark) AECNO TL (manufactured by ARKEMA, nylon 12), grill amide L25 (manufactured by MSK Japan), and the like. Moreover, as an example of the commercial item of the said nylon elastomer, grill flex ELG5660, grill flex ELG6260 (above, the product made by M Chemie Japan Co., Ltd.), etc. are mentioned. Of these, a stretchable material is preferable, and the balloon is preferably biaxially stretched having high strength and expansion force, as will be described in detail below.

  When the balloon contains a near-infrared fluorescent dye, the mixing ratio of the near-infrared fluorescent dye and the balloon-forming material is such that the near-infrared is sufficiently visible when irradiated with near-infrared light having a wavelength of 500 nm to 1400 nm. The ratio is not particularly limited as long as it emits fluorescence. Specifically, it is preferable to add 0.001 to 10.0 parts by weight of the near-infrared fluorescent dye with respect to 100 parts by weight of the balloon-forming material. More preferably, the ratio is from 01 to 1.0 part by weight. If it is such a ratio, when near-infrared rays with a wavelength of 500 nm to 1400 nm are irradiated, near-infrared fluorescence is emitted to such an extent that the balloon is sufficiently visible, and the expandability, strength, flexibility, etc. of the balloon are also improved. Enough can be secured.

  Moreover, the manufacturing method of a balloon is not limited to the following, A well-known manufacturing method can be applied similarly or suitably selected. Specifically, blow molding, extrusion molding, injection molding, rotational molding, blow molding, transfer molding, press molding, a solution casting method, or the like can be preferably used. Of these, extrusion molding, blow molding, and injection molding are preferable, and blow molding is particularly preferable. More specifically, the balloon can be manufactured by biaxial stretch blow molding as described below. First, a tube (cylinder) made of the above-described material is stretched to a predetermined length at an appropriate temperature (for example, 15 to 300 ° C.). Thereby, the tube is stretched in the axial direction (longitudinal direction of the stent delivery system). Next, the stretched tube is expanded in a mold and blow-molded. The molding space (cavity) of the mold is substantially the same shape as the balloon when expanded. In the mold, a high-pressure gas such as nitrogen gas is injected into the tube. In this blow molding, the temperature of the tube is raised by heating the mold, the tube is softened and expanded in the radial direction. Thus, the tube is stretched in a direction different from the axial stretch performed first, and as a result, a balloon by biaxial stretching is obtained. The axial stretching of the tube may be performed after blow molding, or may be performed simultaneously with the expansion of the tube in the radial direction in the mold, that is, simultaneously with blow molding. With such a manufacturing method, it is possible to easily manufacture a balloon with high dimensional accuracy and little variation in shape, film strength, characteristics, and the like.

  The size of the balloon is not particularly limited, and a size similar to a known one generally used for a ureteral catheter is applied. Specifically, the balloon has a size such that the outer diameter of the cylindrical part (expandable part) when expanded is preferably 1.5 to 6 mm, more preferably 2 to 4 mm. Further, the balloon has a size such that the length of the expandable portion (straight tube portion) is preferably 5 to 50 mm, more preferably 5 to 30 mm.

  In addition to or instead of the balloon, the ureteral catheter of the present invention may further have a hydrophilic surface layer at least partially. By providing the hydrophilic surface layer in this manner, when the ureteral catheter is inserted into the ureter, it exhibits hydrophilicity (lubricity), so that damage to the ureter (particularly the ureteral wall) can be reduced, and surgery is performed. The operability by the user can be improved. Here, the arrangement | positioning form in particular of a hydrophilic surface layer is not restrict | limited, For example, any form etc. which form a hydrophilic surface layer in part or all on the surface of a ureteral catheter may be sufficient.

  The hydrophilic polymer constituting the hydrophilic surface layer may be any polymer as long as it exhibits hydrophilicity (lubricity) when in contact with body fluids. Specifically, it can be prepared with hydrophilic polymers such as plant-based and animal-based natural water-soluble polymers, semi-synthetic water-soluble polymers, synthetic water-soluble polymers. For example, polyvinyl pyrrolidone, acrylic acid polymer, polyvinyl alcohol, ethylene vinyl alcohol such as polyvinyl methyl ether, polyethylene glycol, cellulose derivatives such as cellulose, methyl cellulose and hydroxypropyl cellulose, mannan, chitosan, guar gum, xanthan gum, gum arabic, Examples thereof include sugars such as glucose and sucrose, amino acids such as glycine, gelatin and serine or derivatives thereof, and natural substances such as polylactic acid, sodium alginate and casein.

  When forming a hydrophilic surface layer made of a hydrophilic polymer, the ureteral catheter is immersed in a solution in which the hydrophilic polymer is dissolved (hereinafter also abbreviated as “hydrophilic polymer solution”) and then dried. A hydrophilic surface layer is formed by heat treatment or the like. In the state where the ureteral catheter is immersed in the hydrophilic polymer solution, the inside of the system is depressurized and degassed, so that the solution can quickly penetrate into the narrow and narrow inner surface of the catheter to form a hydrophilic surface layer. It may be promoted. In addition, instead of the method (immersion method or dipping method) of immersing the ureteral catheter in the hydrophilic polymer solution, for example, coating / printing method, spraying method (spraying method), spin coating method, mixed solution impregnated sponge A conventionally known method such as a coating method can be applied to coat the ureteral catheter with the hydrophilic polymer.

  In the following, a urinary catheter is immersed in a hydrophilic polymer solution, the hydrophilic polymer solution (coating solution) is coated on the surface of the urinary catheter, and then a hydrophilic surface layer is formed by a heating operation. This will be described in detail by taking the form as an example. However, the present invention is not limited to these coating and reaction processing operations.

  Examples of the solvent used for dissolving the hydrophilic polymer include N, N′-dimethylformamide (DMF), chloroform, acetone, tetrahydrofuran, dioxane, benzene and the like. Is not to be done. These may be used alone or in combination of two or more.

  The concentration of the hydrophilic polymer solution used for forming the hydrophilic surface layer is not particularly limited, and can be appropriately selected in consideration of the desired thickness and uniformity of the hydrophilic surface layer. With such a concentration, a uniform hydrophilic surface layer can be formed, and when a hydrophilic surface layer is formed inside the catheter, even a narrow and narrow inner surface of the catheter can be covered quickly. However, even if it is out of the above range, it can be sufficiently utilized as long as it does not affect the operational effects of the present invention.

  Moreover, it does not restrict | limit especially as heating conditions (reaction conditions) after apply | coating a hydrophilic polymer solution, What is necessary is just to determine suitably according to the temperature characteristic (heat resistance) of the material which comprises a catheter. For example, the heat treatment temperature (set temperature of a heating apparatus such as a heating furnace) is preferably 10 to 200 ° C, more preferably 10 to 100 ° C. The heating time is not particularly limited, but is preferably 5 minutes to 24 hours. As the heating means (device), for example, an oven, a dryer, a microwave heating device, or the like can be used.

  The hydrophilic surface layer has only to have a thickness that can permanently exhibit excellent surface hydrophilicity (surface lubricity) at the time of use. The thickness of 1 μm or more is sufficient, and preferably 1 mm or less. If the thickness of the hydrophilic surface layer when not swollen is in such a range, layer formation is easy, and the hydrophilicity (lubricity) of the surface can be sufficiently exhibited when contacting body fluid. In addition, when inserting a ureteral catheter, it can be easily inserted without damaging the ureteral wall even if the clearance with the ureter is small (for example, the peripheral ureter). it can. After the formation of the hydrophilic surface layer, it is possible to wash the excess hydrophilic polymer with an appropriate solvent and leave only the hydrophilic polymer firmly fixed on the catheter surface.

  The hydrophilic surface layer thus formed can absorb water at the patient's body temperature (30 to 40 ° C.) and exhibit hydrophilicity (lubricity).

  The ureteral catheter of the present invention as described above can visually recognize the ureteral catheter by irradiating near infrared light with a selected wavelength. Further, since near-infrared light excellent in the permeability of the living body is used for visual recognition of the catheter, the ureteral catheter introduced into the living body can be confirmed noninvasively and satisfactorily. In addition, urine that emits near-infrared fluorescence even after ureteral stenosis / adhesion due to tumors, uterine fibroids, endometriosis, etc., in which the normal ureteral state (eg, presence or absence of meandering or stenosis) is difficult to confirm Since the travel of the ureter along the introduction route of the ureter catheter can be easily confirmed, it is possible to correct the meandering and stenosis of the ureter and to peel the ureter by dilatation and surgery. In addition, since the ureteral catheter of the present invention has a urination hole (urine excretion hole), by placing it, it is possible to prevent a transient increase in urine pressure in the renal pelvis and to avoid obstructive nephritis and hydronephrosis. In addition, even in a long-term operation method, since a urination hole is held inside the ureteral catheter, there are no side effects such as hydronephrosis. In addition, according to the ureteral catheter of the present invention, the near-infrared fluorescence emitted by the near-infrared fluorescent dye does not generate heat even after a long time, and the device itself is simple. Therefore, it is possible to reduce damage to surrounding tissues due to heat generated by the ureteral catheter. Therefore, the ureteral catheter of the present invention can be suitably used for treatments such as dilatation / detachment of the ureter, urine drainage (urine excretion), and urinary stone removal.

  Therefore, the present invention also provides a ureteral catheter according to the present invention, a light source for irradiating near-infrared light having a wavelength of 500 nm to 1400 nm, a camera for receiving near-infrared fluorescence emitted by a near-infrared fluorescent dye upon the irradiation, and The present invention relates to a ureteral catheter position confirmation system having a monitor for confirming an image captured by the camera.

  Hereinafter, a procedure for placing the ureter in the ureter using the ureter catheter of the present invention will be described with reference to the drawings. In addition, the following procedure demonstrates preferable embodiment, and this invention is not limited to the following usage method. The ureteral catheter of the present invention can be used in the same manner for indwelling a normal catheter in the ureter. In the following description, FIG. 3 uses the ureteral catheter of FIG. 1 of the present invention and FIG. 4 uses the ureteral catheter of FIG. 2 of the present invention. Other forms of ureteral catheter may be used instead of the vascular catheter.

  3A to 3C are views for explaining a procedure for indwelling in the ureter using the ureteral catheter of FIG. 1 of the present invention. First, under the cystoscope, the guide wire 22 is inserted into the urethra 14 from the external urethral opening 16 and placed so that the distal end portion passes through the ureter opening 15 and enters the ureter 12 (FIG. 3A). When the ureter is stenotic or occluded, it is preferable to insert the guide wire 22 through the stenosis or occlusion to the kidney 11 (renal pelvis) side. Thereby, a ureteral catheter can be easily passed through a stenosis part or an obstruction | occlusion part at the next process. Next, the ureteral catheter 1 was introduced into the ureter 12 through the guide wire 22 and irradiated with near-infrared light as follows, so that the ureteral catheter 1 was placed at a predetermined position. Is confirmed, the guide wire 22 is removed (FIG. 3B). At this time, the near-infrared light 17 having a specific wavelength is emitted from the light source 18, the near-infrared fluorescence emitted from the near-infrared fluorescent dye is received by the camera 19, and the ureteral catheter image 20 captured by the camera 19 is displayed on the monitor 21. By projecting, the running state of the ureteral catheter 1 can be confirmed (FIG. 3C). As a result, the urinary catheter 1 is safely placed in the ureter 12, and urine is continuously discharged out of the body through the urination hole 2 installed at the distal end of the urinary catheter 1.

  In the above embodiment, the ureteral catheter is inserted into the ureter through the guide wire. However, the ureteral catheter may be inserted into the ureter without using the guide wire. In this case, the ureteral catheter is directly introduced into the ureter under the cystoscope, and the ureteral catheter is placed at a predetermined position while irradiating near infrared light and visually observing the ureteral catheter 1 with a monitor. Good. Alternatively, a ureteral catheter may be inserted into the ureter via an endoscope.

  In FIG. 3, the ureteral catheter of FIG. 1 is used. However, in the present invention, the ureteral catheter of FIG. 2 may be used instead of the ureteral catheter of FIG. Hereinafter, a method for discharging (excreting) urine using the ureteral catheter of FIG. 2 will be described with reference to FIG. FIG. 4 is a diagram illustrating a procedure for placing the ureter in the ureter using the ureteral catheter of FIG. 2 of the present invention. In the same manner as described above, the ureteral catheter is inserted to a predetermined position in the ureter with or without a guide wire or through an endoscope. After confirming that the balloon 6 portion of the ureteral catheter 1 has reached a desired position in the ureter 12 by near-infrared irradiation, liquid or gas is introduced from the balloon joint 7 to expand the balloon 6 (see FIG. 4). As a result, the urinary catheter 1 is safely and reliably placed in the ureter 12, and the urine is continuously discharged out of the body through the urination hole 2 installed at the distal end of the urinary catheter 1. Further, by installing the balloon 6, the balloon can be clearly visualized by expanding the balloon to the ureteral adhesion portion in the ureter, and the ureter can be safely removed by surgery. In such a case, even if the urinary catheter is placed in the long-lasting ureter, movement from the position initially fixed by the balloon can be suppressed, so urine can be discharged out of the body for a longer period of time. it can.

  According to the ureteral catheter 1 of the present invention, urine can be discharged (excreted) in a natural state via the urination hole 2 and the lumen lumen 3. However, when it is difficult to excrete (excrete) due to renal failure or the like, if necessary, a syringe or a suction machine is connected to the connection body 4 and suctioned to a negative pressure to forcibly urine. It may be discharged (excreted). In addition, when the ureter is stenotic, depending on the stenotic site, urinary drainage (excretion) may be insufficient with the placement of one ureteral catheter. In such a case, two or more ureteral catheters may be inserted to more efficiently discharge (excrete) urine.

  Thereby, urine can be efficiently discharged (excreted) by a simple method. The timing of removing the ureteral catheter may vary depending on the symptoms and medical condition. Ultimately, the doctor will be able to identify symptoms of urination disorders (eg hydronephrosis, inflammation, swelling of the face and feet). The decision is made based on comprehensive judgment of improvement. By performing this treatment, suppress ureteritis, relieve or treat obstructive nephritis, renal failure, diagnose the cause of poor urinary flow, treat the cause of poor urine flow Can be determined and secured.

  Moreover, in the said method, the light source 18 which irradiates the near-infrared ray 17 of a specific wavelength, the camera 19 which receives the near-infrared fluorescence which a near-infrared fluorescent dye emits by the said infrared irradiation, the image of the ureteral catheter which the said camera 19 image | photographed Although the apparatus (system) for visually recognizing the ureteral catheter having the monitor 21 is used, the apparatus (system) for visually recognizing the ureteral catheter is not particularly limited to the above, and is a known apparatus (system). Can be used. For example, an imaging apparatus that captures and images near-infrared fluorescence emitted by an excited near-infrared fluorescent dye is included in the constituent elements. The imaging device is capable of capturing near-infrared fluorescence, and is provided with an objective lens that forms an image of the captured near-infrared fluorescence and a lens that expands the image formed by the objective lens. The apparatus may include an infrared transmission filter that does not transmit the elastically scattered light of the laser. The infrared transmission filter is not particularly limited as long as it does not transmit the elastic scattered light of the laser used. As long as the above conditions are satisfied, the material of the infrared transmission filter is not limited, and examples of the material include glass, acrylic, plastic, and hard vinyl chloride. The device may include an infrared scope. The infrared scope is not particularly limited as long as it can detect infrared imaging and can project infrared imaging. An example is an infrared scope developed for medical devices. The infrared scope may include a photographing device for photographing an image projected on the infrared scope. The photographing apparatus is not particularly limited, and examples thereof include a CCD camera developed for research equipment such as a microscope, a commercially available still camera, and a digital camera. An adapter or a hood may be installed between the infrared scope and the camera so that focusing can be performed more easily. When using a still camera, an infrared film is used. The video to be taken may be a still image or a video. A display device that can display an image captured by the imaging device can be connected to the imaging device. The display device is not particularly limited, and examples thereof include general cathode ray tube monitors and liquid crystal monitors. When a personal computer monitor is used as the display device, it is possible to connect to the monitor after passing through the personal computer body. A video recording device capable of recording video can be connected to at least one of the photographing device and the display device. When the video recording device is connected to the photographing device, the still image or the moving image photographed by the photographing device is recorded, and when the video recording device is connected to the display device, the display device displays. Record still images or moving images. The recording method is not particularly limited, and examples thereof include a method using a medium capable of recording image information magnetically, optically, electrically, and magneto-optically, and a device for recording on the medium. Specific examples of media include hard disk, magnetic tape, compact flash (registered trademark) memory, MO disk (magnet optical disk), CDR (writable CD (compact disk)), CDRW (rewritable CD). ), DVDR (writable DVD (digital video disc)), DVDRW (rewritable DVD), BDR, BDRW, and the like. As a device for recording on a medium, a device suitable for the medium is used.

  Alternatively, the device for visually recognizing the ureteral catheter includes a light source unit that emits near-infrared light, and an imaging unit that receives reflected light and / or scattered light from the near-infrared fluorescent dye-containing unit of the catheter emitted from the light source unit. It may have. In this apparatus, near infrared rays emitted from a light source unit are reflected and / or scattered by a catheter unit containing a near infrared fluorescent dye, and the reflected light and / or scattered light is received by an imaging unit. For this reason, the light source unit and / or the imaging unit may include an exposure unit that transmits near infrared rays having a wavelength in the range of 500 nm to 1400 nm. Thereby, in the light source part and the image pick-up part, since the near infrared rays of the limited wavelength range are radiated or received, the ureteral catheter can be visually recognized better. In addition to the exposure unit or instead of the exposure unit, the light source unit and / or the imaging unit may include a polarization unit that transmits near infrared rays having a polarization plane in a desired direction. Thereby, since the light source part or the imaging part emits or receives only near-infrared light having a polarization plane in a desired direction transmitted by the polarizing part, the ureteral catheter can be visually recognized better. In addition to or instead of the above, the apparatus may include an output unit that displays or outputs a signal of data relating to reflected light and / or scattered light received by the imaging unit as an image. As a result, the output unit can display or signal output data relating to the reflected light and / or scattered light received by the imaging unit as an image. In this case, the apparatus stores an optical information storage unit that stores data relating to reflected light and / or scattered light received by the imaging unit in a readable manner, and data relating to reflected light and / or scattered light from the optical information storage unit. And an analysis unit that reads out and analyzes a frequency spectrum and / or luminance distribution of reflected light and / or scattered light, and an output unit displays data on the frequency spectrum and / or luminance distribution obtained by the analysis unit as an image. Display or signal output. The optical information storage unit stores the data related to the reflected light and / or scattered light received by the imaging unit in a readable manner, and the analysis unit reads the data related to the reflected light and / or scattered light from the optical information storage unit and reflects the data. The frequency spectrum and / or luminance distribution of the light and / or scattered light can be analyzed, and the output unit can display or signal output data regarding the frequency spectrum and / or luminance distribution obtained by the analyzing unit as an image.

  The near-infrared light irradiating means and the light receiving means are not particularly limited. For example, a light emitting diode may be used as the irradiating means, and a light receiving means may be configured as a photodiode. Since the light-emitting diode and the photodiode are small and available at low cost, the technique can be performed with small size and low cost. Moreover, the optical axis of the light irradiated by the light irradiation unit and the optical axis of the light received by the light receiving unit may be arranged on the same axis. Since the shortest path length of the light until the irradiated light reaches the light receiving means is shortened, it becomes easy to reach the light receiving means even if the intensity of the irradiated light is weak, and the detection sensitivity for weakly irradiated light is increased. As a result, the information on the shallower portion becomes accurate and the obtained biological density measurement value becomes accurate, so that a highly accurate density measuring device can be realized.

1 ... Ureteral catheter,
2 ... urination hole,
3 ... Lumen lumen,
4 ... Connector,
5 ... Ureteral catheter body,
6 ... Balloon,
7 ... Balloon joint,
11 ... Kidney,
12 ... Ureteral,
13 ... Bladder,
14 ... urethra,
15 ... Ureteral opening,
16 ... External urethral orifice,
17 ... Near infrared,
18 ... light source,
19 ... Camera,
20 ... Image,
21 ... Monitor,
22: Guide wire.

Claims (6)

  A ureteral catheter having one or more lumen lumens including a near-infrared fluorescent dye that emits near-infrared fluorescence when irradiated with near-infrared light having a wavelength of 500 nm to 1400 nm. The near-infrared fluorescent dye has the following formula (1):
X represents an unsubstituted or substituted aryl group or an unsubstituted or substituted heteroaryl group;
Each R ¹ independently represents an alkyl group having 1 to 12 carbon atoms, an aryl group, an arylethenyl group, an arylethynyl group, an alkoxy group having 1 to 12 carbon atoms, an aryloxy group, or a halogen atom; Alternatively, one R ¹ represents —O—C (═O) — and is bonded to X to form a 6-membered ring, and the other R ¹ represents an alkyl having 1 to 12 carbon atoms. A group, an aryl group, an arylethenyl group, an arylethynyl group, an alkoxy group having 1 to 12 carbon atoms, an aryloxy group or a halogen atom;
R ² and R ³ are connected to each other to —O—, —S—, or —N (R ⁸ ) — (wherein R ⁸ represents a hydrogen atom or an alkyl group having 1 to 12 carbon atoms). And R ⁴ and R ⁵ represent a hydrogen atom, or R ⁴ and R ⁵ are linked together to —O—, —S—, or —N (R ⁸ ) — (where R 4 ⁸ represents a hydrogen atom or an alkyl group having 1 to 12 carbon atoms), and R ² and R ³ represent a hydrogen atom;
R ⁶ and R ⁷ each independently represent a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an unsubstituted or substituted aryl group, or an unsubstituted or substituted heteroaryl group. ;
The substituent of the aryl group or heteroaryl group includes a nitro group, a cyano group, an alkoxycarbonyl group having 2 to 13 carbon atoms, an alkyl group having 1 to 12 carbon atoms, a formula: —NH (R ⁹ ) (wherein , R ⁹ represents an alkyl group having 1 to 12 carbon atoms), a mono (alkyl) amino group, a formula: —N (R ⁹ ) ₂ (wherein R ⁹ independently represents the number of carbon atoms A di (alkyl) amino group, a carboxyl group, a hydroxyl group or an alkoxy group having 1 to 12 carbon atoms.
Or an azo-boron complex compound represented by the following formula (2):
However, X and R < ² > -R < ⁷ > are the definitions similar to the said Formula (1),
The ureteral catheter of Claim 1 containing the hydrazone compound shown by these.   At least a portion of the ureteral catheter is formed of a material containing the near infrared fluorescent dye, or at least a portion of the surface of the catheter or lumen lumen is coated with a material containing the near infrared fluorescent dye, The ureteral catheter according to claim 1 or 2. The near-infrared fluorescent dye has the following formulas (3) to (5):
However, X and R < ¹ > -R < ⁷ > are the definitions similar to the said Formula (1),
The ureteral catheter of any one of Claims 1-3 containing the azo-boron complex compound shown by either.   The ureteral catheter according to any one of claims 1 to 4, further comprising a balloon.   The ureteral catheter according to any one of claims 1 to 5, further comprising a hydrophilic surface layer at least partially.