Irrigation fluid for lithotripsy

Abstract

This technology provides an approach that can improve the efficiency of stone fragmentation while suppressing the occurrence of thermal damage. [Solution] The irrigation fluid used for lithotripsy using a femtosecond laser contains silver.

Description

Technical Field

[0001] The present disclosure relates to an irrigation solution for lithotripsy.

Background Art

[0002] Due to changes in eating habits and the increase in lifestyle diseases, the number of patients with urinary stones is steadily increasing worldwide. Approximately 95% of urinary stones are upper urinary tract stones (kidney stones and ureteral stones), and the treatment methods are roughly classified into extracorporeal shock wave lithotripsy, transurethral lithotripsy, and percutaneous lithotripsy. In most cases of transurethral lithotripsy and some cases of percutaneous lithotripsy, lithotripsy using a laser is performed. For example, Patent Document 1 discloses a laser treatment device used for transurethral lithotripsy and the like.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] As a laser used for lithotripsy, a holmium yag laser is often used. However, although the holmium yag laser has high lithotripsy efficiency, heat damage may occur. In particular, when lithotripsy is difficult, such as in the case of stones that are anatomically difficult to access, hard stones, or large stones, the laser output and frequency may be increased, making heat damage more likely to occur. On the other hand, if the energy of the irradiated laser is lowered, it takes time to break the stones, and the risk of urinary tract infection increases. Therefore, there is a need for a technology that can increase the lithotripsy efficiency while suppressing the occurrence of heat damage.

Means for Solving the Problems

[0005] This disclosure can be implemented in the following forms:

[0006] (1) According to one embodiment of the present disclosure, an irrigation fluid for lithotripsy is provided. This irrigation fluid for lithotripsy is an irrigation fluid for lithotripsy using a femtosecond laser and contains silver. According to this embodiment of the irrigation fluid for lithotripsy, the efficiency of stone fragmentation can be increased while suppressing the occurrence of thermal damage.

[0007] (2) The irrigation fluid for lithotripsy described in (1) above may further contain nitrate ions. This form of irrigation fluid for lithotripsy can improve the efficiency of stone fragmentation while suppressing a decrease in safety.

[0008] (3) In the irrigation fluid for lithotripsy described in (1) or (2) above, the concentration of silver may be 0.6 mM or more and 60 mM or less. This form of irrigation fluid for lithotripsy can improve the efficiency of stone fragmentation while suppressing a decrease in safety.

[0009] Furthermore, this disclosure can be implemented in various forms, for example, in the form of a method for producing irrigation fluid for lithotripsy, a method for fragmenting stones, a lithotripsy kit including a femtosecond laser irradiation device and irrigation fluid, and the use of an aqueous silver nitrate solution for producing irrigation fluid for lithotripsy. [Brief explanation of the drawing]

[0010] [Figure 1] This is a schematic diagram illustrating the procedure of transurethral lithotripsy. [Figure 2] This is an explanatory diagram to explain the estimation mechanism. [Figure 3] This is a schematic diagram illustrating the irradiation of a femtosecond laser in the example. [Figure 4] This is an explanatory diagram showing the results of a clinical sample of kidney stones. [Figure 5] This is an explanatory diagram showing the results of artificially synthesized kidney stones. [Figure 6]This is an explanatory diagram showing a comparison of pore sizes in each group of artificially synthesized stones. [Modes for carrying out the invention]

[0011] Figure 1 is a schematic diagram illustrating the transurethral lithotripsy procedure. In Figure 1, the region 90 containing the stone 10 is shown enlarged on the right side of the page. Generally, in transurethral lithotripsy, a ureteroscope 40 is inserted from the urethra 20 into the interior 32 of the ureter 30, and the stone 10 is observed with a camera and fragmented with a laser 50. Generally, the ureteroscope 40 has multiple channels. Perfusion fluid is continuously flowed through one channel. As a result, the interior 32 of the ureter 30, surrounded by the ureteral wall 34, is filled with perfusion fluid. The laser 50 is passed through the other channels of the ureteroscope 40. The laser 50 is emitted just before reaching the stone 10, causing the stone 10 to be fragmented.

[0012] Conventionally, commonly used holmium YAG lasers primarily fragment kidney stones through photodynamic and photothermal effects. According to the photodynamic effect, the stone is fragmented by the shock wave caused by cavitation generated during laser formation and the subsequent collapse of bubbles. According to the photothermal effect, the stone is fragmented by the heat generated during the formation of the laser bubble. More specifically, the heat from the laser is transferred to the stone, resulting in cavitation in the pores within the stone's crystal, which then fragments the stone.

[0013] According to one embodiment of the present disclosure, an irrigation fluid for lithotripsy is provided. This irrigation fluid for lithotripsy is for lithotripsy using a femtosecond laser and contains silver. The lithotripsy is not particularly limited, but examples include transurethral lithotomy (TUL) and percutaneous nephrolithotripsy (PNL). A femtosecond laser is an ultrashort pulse laser whose pulse width is emitted in units of femtoseconds (one quadrillionth of a second).

[0014] The perfusion fluid of this disclosure, by containing silver, can enhance the efficiency of stone fragmentation. The mechanism by which this enhances stone fragmentation efficiency is not certain, but the following presumed mechanism is hypothesized.

[0015] Figure 2 is an explanatory diagram illustrating the estimated mechanism. When a femtosecond laser is irradiated onto a silver-containing liquid, it is expected that silver crystal particles will form due to the bottom-up effect. The inside of the calculus 10 is generally densely structured in layers, but as shown in Figure 2(a), it is thought that ionized silver ions 60 can penetrate into the interior. As shown in Figure 2(b), when a femtosecond laser 55 is irradiated onto the silver ions 60 that have penetrated into the calculus 10, or colloidal silver or silver nanoparticles, silver crystal particles 70 are formed within the crystal due to the bottom-up effect. As shown in Figure 2(c), it is thought that the generation of these crystal particles 70 causes mechanical strain inside the calculus 10, resulting in the calculus 10 being fractured from the inside. In addition, as shown in Figure 2(c), direct fracture by the femtosecond laser 55, i.e., fracture due to photodynamic and photothermal effects, is also expected. It is thought that the calculus 10 can be efficiently fractured through these combined mechanisms.

[0016] The silver contained in the perfusion fluid is not particularly limited as long as it can be used in vivo, and examples include silver ions, colloidal silver, and silver nanoparticles, but silver ions are preferred from the viewpoint of improving fragmentation efficiency. The perfusion fluid containing silver ions is not particularly limited as long as it can be used in vivo, but an aqueous silver nitrate solution is preferred from the viewpoint of suppressing a decrease in safety. Note that the aqueous silver nitrate solution contains both silver ions and nitrate ions. Since the aqueous silver nitrate solution is expected to have antibacterial and hemostatic effects, it is also considered beneficial in lithotripsy in this respect.

[0017] The concentration of silver in the irrigation fluid is not particularly limited as long as it can be used in the living body. However, from the viewpoint of suppressing a decrease in safety and increasing the stone fragmentation efficiency, it is preferably 0.2 mM or more and 200 mM or less, more preferably 0.6 mM or more and 60 mM or less, and even more preferably 20 mM or more and 60 mM or less.

[0018] In the lithotripsy using the irrigation fluid of the present disclosure, the irradiation conditions of the femtosecond laser are not particularly limited and can be appropriately set according to the conditions such as the size and hardness of the stone. However, compared with the case of using physiological saline as the irrigation fluid, the output of the laser may be set low.

[0019] Here, in the lithotripsy using a holmium:YAG laser, thermal damage may occur. More specifically, ureteral stricture occurs postoperatively in about 3% of cases. In particular, when lithotripsy is difficult, such as in the case of stones that are anatomically difficult to access, hard stones, or large stones, attempts may be made to perform efficient lithotripsy by increasing the laser output and frequency. However, excessively increasing the energy setting increases the risk of tissue damage (mucosal damage, ureteral perforation, ureteral rupture) and bleeding due to accidental irradiation to the urinary tract. In addition, excessively increasing the energy setting causes an increase in the temperature of the irrigation fluid, thereby increasing the risk of tissue damage due to heat.

[0020] On the other hand, in the lithotripsy using a femtosecond laser, the generation of heat is suppressed, so the occurrence of thermal damage can be suppressed. Furthermore, by using the irrigation fluid of the present disclosure, the stone fragmentation efficiency can be increased. Therefore, according to the irrigation fluid of the present disclosure, in lithotripsy, it is possible to increase the stone fragmentation efficiency while suppressing the occurrence of thermal damage. As a result of increasing the stone fragmentation efficiency, the output of the laser can be set low, so the occurrence of urinary tract disorders due to excessive irradiation of the laser can be suppressed. In addition, as a result of increasing the stone fragmentation efficiency, the time required for fragmentation can be shortened, so as a result, the increase in the temperature in the urinary tract can be suppressed, and the occurrence of urinary tract infections and ureteral strictures can be suppressed.

[0021] The irrigation fluid of the present disclosure may be used from the beginning to the end of lithotripsy, or may be used in part of lithotripsy. More specifically, for example, for large or hard stones that are considered difficult to crush, the irrigation fluid of the present disclosure may be used from the beginning of the operation. Also, for example, when lithotripsy becomes difficult during an operation using a physiological saline irrigation fluid, it may be switched to the irrigation fluid of the present disclosure. From the viewpoint of suppressing chemical damage to the mucosa, it is preferable to perform irrigation with physiological saline instead of the irrigation fluid of the present disclosure after the procedure.

Example

[0022] Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to the following examples.

[0023] 1. Materials and methods (1) Materials, etc. An aqueous silver nitrate solution was used as the liquid assumed to be the irrigation fluid. For the preparation of the aqueous silver nitrate solution, silver nitrate (99.9%, manufactured by Sigma-Aldrich) and deionized water with a resistivity of 18.2 MΩcm were used. The aqueous silver nitrate solution was prepared by dissolving silver nitrate in deionized water to a concentration of 30 mM or 300 mM and subjecting it to ultrasonic treatment for 5 to 10 minutes. As stones, two types of stones, clinical specimen stones and synthetic stones, were prepared. The clinical specimen stones were collected from patients who had received laser lithotripsy with a holmium laser. As a result of analysis, the clinical specimen stones were found to be calcium oxalate. The synthetic stones were formed of calcium oxalate. As the femtosecond laser, Pharos (manufactured by Light Conversion) was used. For the evaluation of the stones, a field emission scanning electron microscope (JEOL JSM-6390LV, manufactured by JEOL) was used. FIJI image J was used for image analysis.

[0024] (2) Irradiation with femtosecond laser Figure 3 is a schematic diagram illustrating the irradiation of the femtosecond laser in the examples. Each experiment was conducted by placing one calculus and a silver nitrate aqueous solution in a 10 mm diameter quartz cuvette. The femtosecond laser beam was irradiated onto the calculus through the cuvette using a 40 mm convex lens. The spot diameter of the laser beam was set to approximately 3 mm. The spot size at the focal position after focusing through the 40 mm convex lens was approximately 18 μm. The femtosecond laser was set to a wavelength of 1030 nm, an output of 800 μJ, and a repetition rate of 1.3 kHz. The pulse width was set to 170 fs. The laser was irradiated for 10 minutes in each experiment.

[0025] (3) Statistical analysis The size of the pores formed in artificially synthesized stones was compared. Continuous variables with a normal distribution were expressed as mean ± standard deviation. Repeated measures ANOVA was performed to analyze the differences between the three related groups. After the repeated measures ANOVA, post-hoc comparisons were performed using Bonferroni correction to adjust for multiple comparisons. Data were repeated under three conditions (Group 1: water, Group 2: 30 mM silver nitrate solution, Group 3: 300 mM silver nitrate solution).

[0026] 2.Results Figure 4 is an explanatory diagram showing the results for clinical specimens of gallstones. Figure 5 is an explanatory diagram showing the results for artificially synthesized gallstones. Figures 4 and 5 show representative images before and after femtosecond laser irradiation, as well as SEM images. As shown in Figure 4, in clinical specimens of gallstones, when water was used, no pores were formed in the gallstones even after laser irradiation. In contrast, when silver nitrate aqueous solution was used, pore formation was observed in the area enclosed by the dashed line in Figure 4 after laser irradiation. Also, as shown in Figure 5, in artificially synthesized gallstones, when water was used, only slight abrasion of the gallstone surface occurred after laser irradiation. In contrast, when silver nitrate aqueous solution was used, pore formation was observed in the gallstones after laser irradiation. As shown in the SEM images of Figures 4 and 5, silver crystals, shown in white, were observed around the pores formed in the gallstones.

[0027] Figure 6 is an explanatory diagram showing the results of comparing pore sizes in each group of artificially synthesized stones. Repeated measures ANOVA was performed to compare the mean values ​​among the three related groups for artificially synthesized stones. The analysis revealed a statistically significant effect of the groups on the outcome variable, with an F-value of 25.02 and a p-value of 0.00123. To further investigate the significance of the differences, a post-hoc pairwise comparison was performed using a pooled t-test and Bonferroni correction for multiple comparisons. The pore size formed in Group 1, which used water, was significantly smaller than that of Group 2 (p=0.002) using 30 mM silver nitrate solution and Group 3 (p=0.0036) using 300 mM silver nitrate solution. There was no significant difference between Group 2 (30 mM silver nitrate solution) and Group 3 (300 mM silver nitrate solution).

[0028] Based on the above results, it was found that pores could be formed in both clinically sourced and artificially synthesized lithotripsy specimens by irradiating them with a femtosecond laser in a silver nitrate aqueous solution. Since no pores were formed when the femtosecond laser was irradiated under the same conditions in water, it can be said that the efficiency of lithotripsy was improved by using a silver nitrate aqueous solution. In this example, laser irradiation was performed through a quartz cuvette, but in clinical lithotripsy, the laser is irradiated directly onto the lithotripsy in the perfusion fluid. As a result, higher crushing efficiency can be expected.

[0029] The present invention is not limited to the embodiments described above, and can be realized in various configurations without departing from its spirit. For example, the technical features in the embodiments and examples corresponding to the technical features in each form described in the summary of the invention can be replaced or combined as appropriate in order to solve some or all of the above-described problems, or to achieve some or all of the above-described effects. Furthermore, if a technical feature is not described as essential in this specification, it can be deleted as appropriate. [Explanation of symbols]

[0030] 10...Kidney stone, 20...Urethra, 30...Ureter, 32...Internal, 34...Ureteral wall, 40...Ureteroscopy, 50...Laser, 55...Femtosecond laser, 60...Silver ion, 70...Silver crystal particles, 90...Region

Claims

1. A irrigation fluid for lithotripsy using a femtosecond laser, containing silver Irrigation fluid for lithotripsy.

2. In the irrigation fluid for lithotripsy according to claim 1, further, Contains nitrate ions, Irrigation fluid for lithotripsy.

3. In the irrigation fluid for lithotripsy according to claim 1 or claim 2, The concentration of the silver is 0.6 mM or more and 60 mM or less. Irrigation fluid for lithotripsy.

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