JP7273851B2 - Endotoxin deactivation device and deactivation method - Google Patents

Description

TECHNICAL FIELD The present invention relates to an endotoxin deactivation apparatus and a deactivation method.

Endotoxins are lipopolysaccharides that make up the cell walls of Gram-negative bacteria and function as pyrogens even after the Gram-negative bacteria have died. For example, when picogram [pg] or nanogram [ng] units of endotoxin enter the blood, various biological reactions such as fever are induced.

For example, according to Non-Patent Document 1, the dialysate water quality standard is defined as follows. note that. Regarding the unit of numerical values below, CFU is an abbreviation for Colony Forming Unit, and CFU/mL indicates the number of bacteria in 1 mL of solvent. Moreover, EU refers to an endotoxin unit (Endotoxin Unit).

・Dialysis water Bacteria less than 100 CFU/mL Endotoxins less than 0.050 EU/mL Standard dialysate Bacteria Less than 100 CFU/mL Endotoxins less than 0.050 EU/mL ・Ultra-pure dialysate Bacteria Less than 0.1 CFU/mL Endotoxins less than 0.001 EU/mL ( measurement sensitivity)

Ultrafiltration modules are currently used for endotoxin removal. It is defined in JIS K 3824 as a method for confirming the performance of ultrafiltration modules. Also, the Japanese Society for Dialysis Medicine has established endotoxin trapping filter (ETRF) management standards.

Patent Documents 1 and 2 describe methods for decomposing endotoxin. In Patent Literature 1, Pt particles are supported on titanium oxide (photocatalyst), and are irradiated with black light to activate the titanium oxide, thereby decomposing endotoxin. Further, in Patent Document 2, ultraviolet rays activate titanium oxide to decompose endotoxin.

Furthermore, in Non-Patent Document 2, the dialysate is irradiated with ultraviolet rays to prevent the growth of bacteria, thereby suppressing the increase in endotoxin produced from the corpses of the bacteria. Furthermore, in the same document, it is described that endotoxins are removed by combined use of ultraviolet irradiation and ultrafiltration using a so-called ET filter.

Japanese Patent Application Laid-Open No. 2001-286757 JP 2010-227841 A

Michio Mineshima, 5 others, "Dialysate Water Quality Standards 2016", Journal of Japanese Society for Dialysis Therapy (Journal of Dialysis Society), Japan Society for Dialysis Therapy, November 29, 2016, Vol. 49, No. 11, p. 697-725 Minoru Okabe, 4 others, "Effect of ultraviolet irradiation on dialysate", Journal of Japanese Society for Dialysis Medicine (Journal of Dialysis Society), Japan Society for Dialysis Medicine, August 28, 1997, Vol.30, No.8 No., p. 1069-1072

By the way, when a filter is used for removing endotoxin, clogging of the filter occurs during use, resulting in an increase in pressure and a decrease in flow rate, so the filter needs to be replaced periodically.

Accordingly, an object of the present invention is to provide an endotoxin deactivation apparatus and a deactivation method, which can be used as an alternative method for removing endotoxin by a filter, and which can deactivate endotoxin in a liquid to be treated. .

The present invention relates to an endotoxin deactivation treatment apparatus. The device comprises a container or tubing and a light source. The container stores the liquid to be treated. A liquid to be treated flows through the pipe. The light source irradiates the liquid to be treated in the container or pipe with ultraviolet light having a wavelength of less than 365 nm.

As will be described later, according to the findings of the inventors, endotoxin is deactivated by irradiating the liquid to be treated with ultraviolet light having a wavelength of less than 365 nm.

Further, in the above invention, the wavelength of the ultraviolet rays emitted from the light source may be 300 nm or less.

Further, in the above invention, the wavelength of the ultraviolet rays emitted from the light source may be 285 nm or less.

Further, in the above invention, the wavelength of the ultraviolet rays emitted from the light source may be 270 nm or less.

Further, in the above invention, a heater may be provided for heating the liquid to be treated to a temperature of 40° C. or higher and lower than the boiling point of the liquid to be treated.

As will be described later, the inventors found that the deactivation of endotoxin is accelerated by heating the liquid to be treated during ultraviolet irradiation. As a result, the endotoxin concentration can be reduced in a shorter period of time than when heating is not performed.

Moreover, in the above invention, the light source may be a deep ultraviolet LED.

Further, in the above invention, the irradiance of the ultraviolet rays emitted from the deep ultraviolet LED on the liquid to be treated may be 3 mW/cm ² or more.

The present invention also relates to a method for deactivating endotoxin. In this method, the liquid to be treated is stored in a container or circulated through a pipe. Furthermore, the liquid to be treated in the container or pipe is irradiated with ultraviolet light having a wavelength of less than 365 nm.

In the above invention, the liquid to be treated may be irradiated with ultraviolet light having a wavelength of 300 nm or less.

In the above invention, the liquid to be treated may be irradiated with ultraviolet light having a wavelength of 285 nm or less.

In the above invention, the liquid to be treated may be irradiated with ultraviolet rays having a wavelength of 270 nm or less.

Further, in the above invention, the liquid to be treated may be heated to a temperature of 40° C. or higher and lower than the boiling point of the liquid to be treated during the ultraviolet irradiation.

In the above invention, a deep ultraviolet LED may be used as the light source to irradiate the liquid to be treated with ultraviolet light.

Further, in the above invention, the irradiance of the ultraviolet rays emitted from the deep ultraviolet LED on the liquid to be treated may be 3 mW/cm ² or more.

INDUSTRIAL APPLICABILITY According to the present invention, endotoxin in a liquid to be treated can be inactivated, which can be an alternative method for removing endotoxin by a filter.

BRIEF DESCRIPTION OF THE DRAWINGS It is a figure which illustrates the endotoxin deactivation apparatus which concerns on this embodiment. 4 is a graph showing changes in endotoxin concentration in the liquid to be treated when the liquid to be treated is irradiated with ultraviolet rays. 4 is a graph showing changes in the concentration of endotoxin in the liquid to be treated when the liquid to be treated is heated when irradiated with ultraviolet rays, in comparison with the case of non-heating. As a comparative example, it is a graph which shows the change of the endotoxin density|concentration in the to-be-processed liquid when only heating is given to to-be-processed liquid, without irradiating an ultraviolet-ray. It is a figure which shows another example of the endotoxin deactivation apparatus which concerns on this embodiment. FIG. 6 is a diagram showing another example of the endotoxin deactivation apparatus according to the present embodiment. FIG. 6 is a diagram showing still another example of the endotoxin deactivation apparatus according to the present embodiment. FIG. 6 is a diagram showing still another example of the endotoxin deactivation apparatus according to the present embodiment. FIG. 2 is a diagram illustrating a light source of the endotoxin deactivation apparatus according to the present embodiment; FIG. 5 is a diagram showing another example of the light source of the endotoxin deactivation apparatus according to the present embodiment. FIG. 6 is a diagram showing still another example of the endotoxin deactivation apparatus according to the present embodiment. It is a sectional view explaining the structure of the irradiation device concerning this embodiment. 4 is a graph showing temporal changes in endotoxin concentration in the liquid to be treated under UV irradiation/non-irradiation and heating/non-heating conditions, respectively.

FIG. 1 illustrates an endotoxin deactivation treatment apparatus 10 according to this embodiment. The endotoxin deactivation treatment device 10 includes a light source 12 , a container 14 and a heater 16 .

The container 14 is composed of, for example, a glass beaker, a resin beaker, or the like. Also, the container 14 may be, for example, a heat-resistant glass beaker or a heat-resistant resin beaker such as Teflon (registered trademark) so that it can withstand the heating by the heater 16 . Also, the container 14 may be made of a non-magnetic material so as to enable stirring inside the container 14, which will be described later.

Furthermore, the container 14 stores the liquid 20 to be processed. For example, the container 14 contains only the liquid 20 to be treated and the rotor 18 .

The liquid to be treated 20 is, for example, water for injection, water used for dialysate, and dialysate itself, which is a raw material for so-called endotoxin-free water (sterilized water). Distilled water or the like may be used.

The heater 16 heats the liquid to be treated 20 in the container 14 . Heater 16 may be, for example, a hot plate. The temperature range that can be heated by the heater 16 may be 40° C. or higher and lower than the boiling point of the liquid 20 to be treated. For example, the heatable temperature range of the heater 16 may be 40°C or higher and lower than 100°C.

Alternatively, a heat sink of the light source 12 may be connected to the container 14 as the heater 16 . By doing so, the waste heat of the light source 12 can be used to heat the container 14 .

In addition, the heater 16 may have a stirring function. For example, heater 16 may be a magnetic stirrer with a hot plate. In this case, a rotor 18 consisting of Teflon-coated magnets is placed in the container 14 .

The light source 12 irradiates the liquid to be treated 20 in the container 14 with ultraviolet rays (radiates ultraviolet rays). The irradiation range of the light source 12 is set so as to sufficiently include the container 14 .

Generally, ultraviolet rays refer to electromagnetic waves with a wavelength of 100 nm or more and 400 nm or less. Furthermore, the wavelength range of ultraviolet rays is subdivided, and electromagnetic waves with wavelengths of 200 nm or more and 300 nm or less are called deep ultraviolet rays.

The light source 12 irradiates electromagnetic waves included in the wavelength range of deep ultraviolet rays, that is, ultraviolet rays with a wavelength of 100 nm or more and less than 365 nm. For example, the light source 12 may be capable of irradiating deep ultraviolet rays with a wavelength of 100 nm or more and 300 nm or less. Alternatively, the light source 12 may be capable of emitting deep ultraviolet rays having a wavelength of 100 nm or more and 285 nm or less. Alternatively, the light source 12 may be capable of emitting deep ultraviolet rays having a wavelength of 100 nm or more and 270 nm or less.

Light source 12 may be, for example, a deep UV LED. Alternatively, a low pressure mercury lamp or an excimer lamp may be used as the light source 12 . Among these light sources, it is preferable to use a deep ultraviolet LED, which has a relatively long life. Regarding the output, the irradiance of the deep ultraviolet rays emitted from the light source 12 on the liquid to be treated 20 may be 3 mW/cm ² or more. By irradiating the liquid to be treated 20 with sufficiently intense deep ultraviolet rays, the endotoxin is deactivated.

<Example 1>
An experiment was conducted on the endotoxin deactivation treatment by the light source 12 . As the liquid to be treated 20, sterilized water manufactured by Wako Pure Chemical Industries (endotoxin-free water) is added to the endotoxin standard product to obtain "endotoxin raw water", which is diluted to obtain "endotoxin water" having an endotoxin concentration of about 0.1 EU / ml. "It was created.

Specifically, the endotoxin standard product is, for example, the Japanese Pharmacopoeia standard product sold by Pharmaceuticals and Medical Devices Regulatory Science Foundation, and one bottle contains 10000 endotoxin units (EU) or more of endotoxin. Add this endotoxin standard to a specified volume of endotoxin test water. Water for injection, for example, is used as the water for endotoxin test. An endotoxin raw water is created by stirring both.

2 ml of endotoxin water was sampled and placed in the container 14 and irradiated with ultraviolet rays from the light source 12 . The wavelengths of ultraviolet rays were 270 nm, 285 nm, 300 nm and 365 nm. Also, the irradiance in endotoxin water was set to 3 mW/cm ² at any wavelength. As a comparative example (control experiment), a sample not irradiated with ultraviolet rays was also prepared.

Tables 1, 2, 3, 4 and 5 below show the endotoxin concentrations [EU /ml]. Regarding the irradiation time, for example, when the irradiation time is 0 minutes, the endotoxin concentration indicates the initial concentration. Moreover, when the irradiation time is 60 minutes, it indicates that the ultraviolet rays were irradiated for 60 minutes.

As for the number of samples, three samples were used without UV irradiation, with UV irradiation at 270 nm, with UV irradiation with 285 nm, and with UV irradiation with 300 nm. Also, one sample was used for irradiation with ultraviolet rays of 365 nm. In conducting the experiments of Tables 1 to 5, heating by the heater 16 was not performed, and the magnetic stirrer was turned on to rotate the rotor 18 to stir the liquid to be treated 20 (endotoxin water). rice field. In the following experiments, the endotoxin concentration was measured using Toxinometer Mini manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.

FIG. 2 shows a graph plotting the average endotoxin concentration for each irradiation time in Tables 1 to 4 and the endotoxin concentration for each irradiation time in Table 5. The vertical axis indicates the endotoxin concentration (EU/ml), and the horizontal axis indicates the irradiation time (elapsed time when not irradiated).

Referring to FIG. 2, no reduction in endotoxin concentration is observed at a wavelength of 365 nm, but a significant reduction in endotoxin concentration is observed upon irradiation with deep ultraviolet rays at 300 nm. Furthermore, it is understood that the shorter the wavelength, the greater the decrease in endotoxin concentration.

From this, it is understood that endotoxin is not deactivated by deep ultraviolet irradiation at a wavelength of 365 nm or more. In addition, it is understood that in the wavelength region of less than 365 nm, the smaller the wavelength, the higher the deactivation effect.

Next, an experiment was conducted on changes in endotoxin concentration when the liquid to be treated 20 (endotoxin water) was heated during irradiation with deep ultraviolet rays. Table 6 below shows the plot enclosed by the dashed line in FIG. , and changes in endotoxin concentration when heated at 60° C., respectively. Numbers in the table indicate endotoxin concentration [EU/ml]. The number of samples was 3 for each.

In addition, in the experiment of Table 6, the heating temperature was set by the temperature setting function of the heater 16 (hot plate). In order to heat the endotoxin water, after setting the temperature of the heater 16, irradiation of ultraviolet rays was started after a predetermined waiting time. The amount of endotoxin water (liquid 20 to be treated) injected into the container 14 was 2 ml, and the UV irradiance in the endotoxin water was 3 mW/cm ² . Further, the magnetic stirrer was turned on and the rotor 18 was rotated to stir the liquid to be treated 20 (endotoxin water).

A graph plotting the average values of Table 6 is shown in FIG. The vertical axis indicates the endotoxin concentration [EU/ml]. As shown in this graph, it is understood that the deactivation of endotoxin is promoted by deep ultraviolet irradiation accompanied by heating at 40°C or higher. In particular, heating at 50°C or higher significantly accelerates the deactivation of endotoxin.

For example, referring to the graph in Table 2, when deep ultraviolet rays with a wavelength of 270 nm were irradiated without heating (that is, at room temperature of 25° C.), the average endotoxin concentration after 4 hours was 0.0047 [EU/ml]. reached. On the other hand, referring to Table 6, when heating at 50° C. and 60° C. in addition to irradiation with deep ultraviolet rays having a wavelength of 270 nm, the endotoxin concentration reaches a similar level in 1 hour. That is, by carrying out heating at 50° C. and heating at 60° C., the time can be shortened by about four times.

The graph in FIG. 4 shows the change in endotoxin concentration when only heating was performed without ultraviolet irradiation as a comparative example (control experiment). The heating conditions were the same as those in FIG. 3, and the amount of endotoxin water (liquid 20 to be treated) injected into the container 14 was 2 ml. Further, the magnetic stirrer was turned on and the rotor 18 was rotated to stir the liquid to be treated 20 (endotoxin water).

With reference to the graph of FIG. 4, the endotoxin concentration after 60 minutes is almost constant regardless of the difference in heating temperature and the presence or absence of heating, and no significant difference due to heating is observed. From this, in the temperature range of 40° C. or higher and 60° C. or lower, although the endotoxin deactivation effect was not observed by heating alone, a significant endotoxin deactivation effect was obtained by heating in combination with deep ultraviolet irradiation. It is understood that

In the example of FIG. 1, the container 14 for storing the liquid to be treated (endotoxin water) is used as the endotoxin deactivation apparatus 10, but the apparatus is not limited to this example. For example, pipes 24, 34 and a container 44 through which the liquid flows may be used as illustrated in FIGS.

FIG. 5 illustrates an endotoxin deactivation treatment device 10 having a pipe 24 . The apparatus comprises heater 16 , tubing 24 and light source 12 .

The heater 16 is provided upstream of the pipe 24 and heats the liquid to be treated (endotoxin water). The heated liquid to be processed is fed into the pipe 24 . For example, the liquid to be treated is fed into the pipe 24 by liquid feeding means such as a pump. Alternatively, the pipe 24 may be installed below the heater 16 and the liquid to be treated may flow down the pipe 24 as it is.

A transparent window member 30 is provided at a portion of the pipe 24 , specifically at a position facing the light source 12 . The window member 30 may be quartz glass, for example. Light source 12 may also be a deep UV LED, a low pressure mercury lamp, or an excimer lamp.

The light source 12 emits ultraviolet light having a wavelength of 100 nm or more and less than 365 nm. For example, the light source 12 may be capable of irradiating deep ultraviolet rays with a wavelength of 100 nm or more and 300 nm or less. Alternatively, the light source 12 may be capable of emitting deep ultraviolet rays having a wavelength of 100 nm or more and 285 nm or less. Alternatively, the light source 12 may be capable of emitting deep ultraviolet rays having a wavelength of 100 nm or more and 270 nm or less.

The irradiance of the deep ultraviolet rays emitted from the light source 12 on the liquid to be treated may be 3 mW/cm ² or more. By irradiating the liquid to be treated with sufficiently intense deep ultraviolet rays, the endotoxin is deactivated.

In FIG. 5, the light source 12 is provided at one longitudinal end of the pipe 24, but another light source 12 may be provided at the other end. In this case, the window member 30 is also formed in the pipe 24 facing the other light source 12 .

FIG. 6A illustrates the endotoxin deactivation treatment device 10 having a double pipe structure pipe 34A. Differences from FIG. 5 include that the pipe 34A has a double-pipe structure, and that the light source 12 is shaped like a rod and inserted into the pipe 34A (more specifically, the window member 36A). .

As illustrated in the side cross-sectional view and the AA cross-sectional view of FIG. 6A, a cylindrical window member 36A is arranged inside the pipe 34A. The window member 36A is composed of, for example, a quartz tube. A rod-shaped light source 12 is inserted inside the window member 36A.

Also, FIG. 6B illustrates an endotoxin deactivation treatment apparatus 10 that is different from that in FIG. 6A and has a double-pipe structure pipe 34B. As illustrated in the side cross-sectional view of FIG. 6B, the pipe 34B has a concave shape in side cross-sectional view, and a window member 36B is used as the inner container wall. The window member 36B is composed of, for example, a quartz sealing tube. A rod-shaped light source 12 is inserted inside the window member 36B.

FIG. 7 illustrates an endotoxin deactivation treatment apparatus 10 having a different format from those of FIGS. 5, 6A, and 6B. 5, 6A, and 6B, the liquid to be treated (endotoxin water) is filled in the pipes 24, 34A, and 34B so as to be watertight, but in the example of FIG. A space is provided between the surface of the liquid to be treated and the pooled liquid. Furthermore, the light source 12 is provided on the inner surface of the ceiling of the container 44 . The light source 12 may be installed not only on the inner surface of the ceiling of the container 44, but also on the bottom and side surfaces.

The amount of storage in container 44 is adjusted through opening/closing control of inlet valve 40 and outlet valve 42 . After passing through the inlet valve 40, the liquid to be treated passes through the heater 16A and is fed into the container 44. As shown in FIG. Further, the light source 12 irradiates ultraviolet rays within the container 44 . A heater 16B may be provided on the bottom surface of the container 44 to perform irradiation and heating at the same time. After being irradiated with ultraviolet rays, the liquid to be treated is sent out of the container 44 through the outlet valve 42 .

The light source 12 may be a surface light source, and may be a plurality of deep ultraviolet LEDs 50 arranged in a plane as illustrated in FIG. 8, for example. Alternatively, as illustrated in FIG. 9, a plurality of low-pressure mercury lamps 52 may be arranged.

5 to 7, a bypass pipe (return pipe) is provided in the circulation type endotoxin deactivation treatment apparatus 10, and the liquid to be treated sent out from the pipes 24, 34A, 34B and the container 44 is pumped. The pipes 24, 34A, 34B and the container 44 may be returned upstream and irradiated with ultraviolet rays a plurality of times.

<Another example of endotoxin deactivation treatment device>
FIG. 10 shows another example of the endotoxin deactivation treatment apparatus 10 according to this embodiment. The apparatus includes an irradiation device 60 , a tank 90 , an outward piping 92 , a return piping 94 , a pump 96 , a temperature controller 98 , a power supply 100 , a heater 102 and a temperature sensor 104 .

The endotoxin water described above is stored in the tank 90 . The storage capacity of the tank 90 may be, for example, 5L. A heater 102 and a temperature sensor 104 are installed in the tank 90 . The heater 102 may be a so-called immersion heater, and the heat-generating part is kept in the tank 90 . At least the probe of the temperature sensor 104 is placed inside the tank 90 . A temperature sensor 104 measures the temperature of the endotoxin water in the tank 90 heated by the heater 102 . The measured water temperature is sent to temperature controller 98 . Temperature controller 98 controls the operation of heater 102 based on the received water temperature. For example, when the water temperature in the tank 90 reaches the target temperature, the temperature controller 98 controls heat generation of the heater 102 so as to maintain the water temperature.

An upstream end of an outward pipe 92 and a downstream end of a return pipe 94 are inserted into the tank 90 . The endotoxin water in the tank 90 is sucked into the outgoing pipe 92 by the pump 96 . The pump 96 may be, for example, a tube pump, and the circulation flow rate may be, for example, 500 ml/min.

The endotoxin water flowing through the outgoing pipe 92 is sent to the irradiation device 60 . The endotoxin water that has been irradiated with ultraviolet light by the irradiation device 60 is returned to the tank 90 via the return pipe 94 . Thus, the endotoxin water is circulated between the inside of the tank 90 and the irradiation device 60 .

FIG. 11 illustrates a cross-sectional view of the irradiation device 60. As shown in FIG. 11, the orientation of the irradiation device 60 is reversed from that shown in FIG. The irradiation device 60 includes a light source 70 , a cylindrical portion 80 , covers 82 and 84 and a window member 86 .

The cylindrical portion 80 is open at both ends in the longitudinal direction, and covers 82 and 84 are attached to the open ends. The covers 82 and 84 may be made of a resin material such as Teflon, and the cylindrical portion 80 may be made of a resin material such as Teflon or a metal material such as stainless steel. The volume of the cylindrical portion 80 may be, for example, 80 ml. Further, as shown in FIG. 11, when ultraviolet rays are irradiated from the side surface of the cylindrical portion 80, that is, from the radial direction instead of from the longitudinal direction of the cylindrical portion 80, the cylindrical portion 80 is made of quartz glass or the like. A window member may be provided.

The cover 82 is attached to, for example, the open end on the upstream side of the cylindrical portion 80 to seal the open end. The cover 82 is provided with a connection pipe 82A. The connection pipe 82A is connected to the downstream end of the forward pipe 92 (see FIG. 10). The endotoxin water flows into the cylindrical portion 80 from the outgoing pipe 92 via the connecting pipe 82A.

A window member 86 and a cover 84 are attached to the open end of the cylindrical portion 80 on the downstream side. The window member 86 is a transparent member that covers the downstream open end of the cylindrical portion 80 . The window member 86 is made of quartz glass, for example. This window member 86 is fixed to the cylindrical portion 80 by a cover 84 . The cover 84 is axially penetrated at, for example, the center portion in the radial direction, and the through hole 84A functions together with the window member 86 as a light guide portion that allows the ultraviolet rays of the LEDs 72 to pass therethrough.

Further, the cover 84 is provided with a connecting pipe 84A. The connection pipe 84A is connected to the upstream end of the return pipe 94 (see FIG. 10). The endotoxin water in the cylindrical portion 80 flows into the return pipe 94 via the connecting pipe 84A.

Light source 70 comprises a plurality of LEDs 72 , substrate 74 and heat sink 76 . The LEDs 72 may be deep UV LEDs, similar to the embodiments described above. LED 72 is powered by power supply 100 (see FIG. 10).

The LED 72 emits ultraviolet light having a wavelength of 100 nm or more and less than 365 nm. For example, the LED 72 may be capable of emitting deep ultraviolet rays having a wavelength of 100 nm or more and 300 nm or less. Alternatively, the LED 72 may be capable of emitting deep ultraviolet rays having a wavelength of 100 nm or more and 285 nm or less. Alternatively, the LED 72 may be capable of emitting deep ultraviolet rays having a wavelength of 100 nm or more and 270 nm or less. Also, the UV intensity of the LEDs 72 may be, for example, 220 mW.

A plurality of LEDs 72 are mounted on the substrate 74 . For example, by mounting a plurality of LEDs 72 on a substrate 74, a surface light source such as that illustrated in FIG. 8 is configured. Further, a heat sink 76 is provided on the surface opposite to the surface on which the substrate 74 and the LEDs 72 are mounted.

<Example 2>
Using the endotoxin deactivation apparatus 10 illustrated in FIG. 10, an experiment was conducted on endotoxin deactivation by the light source 70 (see FIG. 11). As the liquid to be treated, lipopolysaccharide derived from E. coli 0111 manufactured by Sigma was dissolved in distilled water filtered through an endotoxin-cut filter, and this was prepared as raw endotoxin water. Furthermore, "endotoxin water" was prepared by adjusting the endotoxin raw water to 10 EU/ml or more and 100 EU/ml or less. The amount of endotoxin water was 5L.

Also, in this example, as described above, the endotoxin water was circulated at a flow rate of 500 ml/min. Further, the inside of the cylindrical portion 80 was irradiated with deep ultraviolet rays using the LED 72 with a wavelength of 270 nm. Moreover, the ultraviolet intensity of the LED 72 was set to 220 mW at any wavelength. As a comparative example (control experiment), a sample not irradiated with ultraviolet rays was also prepared.

Also, a sample of 0.3 ml or less was collected from the tank 90 each time, and the concentration was measured. The endotoxin water in the tank 90 was stirred using a magnetic stirrer (not shown).

Table 7 below shows changes in endotoxin concentration over time without UV irradiation and without heating (that is, room temperature of 25° C.). In addition, Table 8 shows the change in endotoxin concentration over time when irradiated with ultraviolet rays of 270 nm. Table 8 shows changes in endotoxin concentration over time under three conditions: no heating (room temperature of 25°C), heating to 40°C, and heating to 50°C.

Regarding the irradiation time, for example, when the irradiation time is 0 minutes, the endotoxin concentration indicates the initial concentration. Moreover, when the irradiation time is 60 minutes, it indicates that the ultraviolet rays were irradiated for 60 minutes. Furthermore, as the endotoxin concentration, the concentration ratio is shown when the concentration at the initial value (elapsed time=0) is set to 1.0.

A graph showing changes in endotoxin concentration over time in Tables 7 and 8 is shown in FIG. The vertical axis indicates the endotoxin concentration, and the horizontal axis indicates the irradiation time (elapsed time when not irradiated). The endotoxin concentration on the vertical axis is expressed in a logarithmic scale with the concentration at the initial value (elapsed time=0) being 1.0.

Referring to FIG. 12, almost no decrease in endotoxin concentration is observed when ultraviolet rays are not irradiated. On the other hand, when ultraviolet rays were irradiated at room temperature (25° C.), the endotoxin concentration decreased to 1/1000 in about 300 minutes. When the tank 90 was heated to 40° C. and irradiated with ultraviolet rays, the endotoxin concentration decreased to 1/1000 in about 180 minutes. Furthermore, when the tank 90 was heated to 50° C. and irradiated with ultraviolet rays, the endotoxin concentration decreased to 1/1000 in about 120 minutes. From these results, it is understood that a significant endotoxin deactivation effect can be obtained by heating in combination with ultraviolet (deep ultraviolet) irradiation.

10 endotoxin deactivation treatment device 12 light source 14, 44 container 16 heater 18 rotor 20 liquid to be treated (endotoxin water) 24, 34A, 34B piping 30 window member 40 inlet valve 42 outlet valve , 60 irradiation device, 70 light source, 80 cylinder, 90 tank, 96 pump, 98 temperature controller, 100 power supply.

Claims (12)

a container for storing endotoxin water containing endotoxin but not containing an additive for deactivation treatment of the endotoxin, or a pipe for circulating the endotoxin water;
a light source that irradiates the endotoxin water in the container or the pipe with ultraviolet rays having a wavelength of less than 365 nm;
a heater for heating the endotoxin water at the time of ultraviolet irradiation to a temperature of 40° C. or more and less than the boiling point of the endotoxin water;
An endotoxin deactivation device. 2. The apparatus for deactivating endotoxin according to claim 1, wherein the ultraviolet light emitted from said light source has a wavelength of 300 nm or less. 3. The apparatus for deactivating endotoxin according to claim 2, wherein the ultraviolet light emitted from said light source has a wavelength of 285 nm or less. 4. The endotoxin deactivation apparatus according to claim 3, wherein the wavelength of the ultraviolet light emitted from said light source is 270 nm or less. The endotoxin deactivation apparatus according to any one of claims 1 to 4,
The light source is a deep UV LED,
Endotoxin deactivation device. The endotoxin deactivation apparatus according to claim 5,
The irradiance of the ultraviolet rays emitted from the deep ultraviolet LED in the endotoxin water is 3 mW/cm ² or more,
Endotoxin deactivation device. storing endotoxin water containing endotoxin but not containing an additive for deactivating the endotoxin in a container or distributing it through a pipe;
irradiating the endotoxin water in the container or pipe with ultraviolet rays having a wavelength of less than 365 nm;
heating the endotoxin water at the time of ultraviolet irradiation to a temperature of 40° C. or more and less than the boiling point of the endotoxin water;
A method for deactivating endotoxin. 8. The method for deactivating endotoxin according to claim 7, wherein the endotoxin water is irradiated with ultraviolet light having a wavelength of 300 nm or less. 9. The method for deactivating endotoxin according to claim 8, wherein the endotoxin water is irradiated with ultraviolet light having a wavelength of 285 nm or less. 10. The method for deactivating endotoxin according to claim 9, wherein the endotoxin water is irradiated with ultraviolet light having a wavelength of 270 nm or less. The endotoxin deactivation method according to any one of claims 7 to 10,
irradiating the endotoxin water with ultraviolet rays using a deep ultraviolet LED as a light source;
A method for deactivating endotoxin. The endotoxin deactivation method according to claim 11,
The irradiance of the ultraviolet rays emitted from the deep ultraviolet LED in the endotoxin water is 3 mW/cm ² or more,
A method for deactivating endotoxin.

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