JPH0835917A - Autosampler for elution test - Google Patents

Abstract

PURPOSE:To provide an autosampler, for an elution test, by which the wear of a liquid-sending tube and a change in a liquid-sending amount are suppressed, whose maintenance control is easy and whose high measuring accuracy can be maintained. CONSTITUTION:An autosampler is provided with an air cylinder 12 for dispensing, with a liquid-sending tube 16 one end of which is opened at a flask 7 and which has a nozzle 40 at the other end, with an air-sending tube 59 one end of which is connected to the air cylinder 12 and which has the nozzle 40 at the other end and with a nozzle movement mechanism part 11 by which the tip part of the nozzle 40 is inserted into, and detached from, a sample bottle 9. When a control part instructs the air cylinder 12 to operate so as to generate a negative pressure inside the sample bottle 9, an elution liquid 90 which is generated by the generated negative pressure is sucked and dispensed to the sample bottle 9 from the flask 7.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an autosampler for dissolution test, and more particularly, to the internal use of tablets etc. for the purpose of ensuring a certain quality of solid preparations for internal use and preventing significant biological inequalities. An autosampler used in the "dissolution test method" prescribed by the Japanese Pharmacopoeia to test the dissolution of main components from solid preparations. Internal solid preparations stored in multiple (usually 6) flasks. The present invention relates to an autosampler for dissolution test for immersing a drug in an equal amount of the drug solution, sampling each drug solution in equal amounts at a set fixed time, and measuring the dissolution rate of the formulation.

[0002]

2. Description of the Related Art An autosampler used in the "dissolution test method" generally includes a storage container 1 for storing an internal solid preparation and a chemical liquid container 2 for storing a replenishing drug solution, as shown in FIG. A sample container 3 in which the eluate is stored,
It is mainly composed of a tube pump (ironing pump) 5. Each container 1, 2, 3 is connected by a tube 4. When performing the dissolution test, first, the dissolution liquid in the container 1 flows from the storage container 1 in which the preparation is dipped in the container 1 by the tube pump 5 in the arrow direction of the solid line in the figure. After the sample amount calculator calculates a predetermined amount of flow rate, the TV valve is switched and the SV valve is opened to sample the predetermined amount of the eluate in the sample container 3. After the sampling is completed, the CV valve is switched and the same amount of the chemical liquid as the sampling amount is replenished in the storage container 1. After the chemical solution is replenished, when the CV valve is switched and the chemical solution flows in the direction of the broken line arrow in the drawing and enters the storage container 1, the tube pump 5 is stopped and stands by until the next sampling. At the next sampling time, the above steps are repeated, and the operation is stopped when the set number of samples are sampled.

As the tube 4, a flexible silicon tube is usually used. However, since plastic deformation is repeated in a short time at a contact portion with the tube pump 5, it is easily damaged. For this reason, the amount of liquid to be sent easily fluctuates, and it is necessary to replace a plurality of tubes at the time of replacement, which makes the replacement work complicated. Further, the eluate contains a small amount of powder, and when this liquid passes through the tube pump 5, the powder is crushed by the rollers and dissolved in the eluate. For this reason, the preparation is considered to be dissolved at an earlier time than it actually is, which is an obstacle to accurate measurement of the dissolution rate.

Further, the eluate eluted from the preparation also contains a paste-like elution substance, and these substances adhere to the solenoid valve, which causes a change in the sample amount or the replenishment liquid amount. Further, since the residual liquid in the valve is mixed with the eluate to be sampled next, the eluent in the sample container 3 is diluted and the measurement accuracy cannot be maintained. Furthermore, if the replenisher remaining in the valve and the substance dissolved in the eluate adhere to the inner surface of the valve as they are, repair is difficult. On the other hand, the drug solution is usually p
Solenoid valve (TV valve, SV
Valve or CV valve) is made of ceramics or Teflon (PT)
The valve made of FE) must be used, which is a factor of high cost.

An object of the present invention is to provide an autosampler for dissolution test, which suppresses wear of the liquid-feeding tube and fluctuations in the liquid-feeding amount, can be easily maintained and maintained, and can maintain high measurement accuracy.

[0006]

The autosampler for dissolution test of the present invention comprises a storage container for storing an internal solid preparation as a dissolution test sample, and a dissolution test chemical solution supplied to the storage container storing the preparation. And a sealable sample container into which the eluate eluted from the formulation is dispensed by the drug solution supplied from the drug solution supply unit, one end of which is opened in the storage container and the other end of which is a first nozzle An eluate delivery tube, a dispensing air cylinder, a gas suction tube having one end connected to the dispensing air cylinder and having a second nozzle at the other end, a first and a second nozzle held, and a tip of each nozzle It is provided with a nozzle moving mechanism that inserts into and removes from the sample container, and a control unit that commands the nozzle moving mechanism and the dispensing air cylinder to operate.

When the control unit commands the dispensing air cylinder to operate so as to generate a negative pressure in the sample container, the generated negative pressure causes the eluate to be sucked and dispensed from the storage container to the sample container. The control unit, when instructing the dispensing air cylinder to operate so as to generate a positive pressure in the sample container,
It is preferable to push back the eluate remaining in the eluate feed tube to the storage container by the generated positive pressure.

The chemical liquid supply section includes a fixed quantity container for containing a fixed amount of the dissolution test chemical liquid to be replenished in the storage container, a chemical liquid supply tube having one end opened to the fixed quantity container and the other end opened to the storage container, and a fixed quantity container. A chemical liquid supply air cylinder having an air discharge port inside is provided, and the control unit further commands the chemical liquid supply air cylinder to generate a positive pressure in the fixed quantity container, and the positive pressure generated at that time causes It is preferable that the drug solution in the fixed quantity container is pressed and transferred to the storage container via the drug solution feeding tube. The sealable sample container in the autosampler for dissolution test of the present invention refers to a container having a septum at the head and a septum having a nozzle inserted therein, which can maintain airtightness in this state.

[0009]

[Function] In the dissolution test autosampler of the present invention,
First, the solid preparation for internal use is stored in a storage container. The control unit
The nozzle moving mechanism is operated to insert the tips of the first and second nozzles into the sample container. Airtightness is maintained in the sample container in which the tip of the nozzle is inserted. The control unit operates the air cylinder to generate a negative pressure in the sample container. As a result, the eluate in the storage container is sucked and dispensed into the sample container. Therefore, when dispensing the eluate into the sample container as in the conventional case, it is possible to suppress the adverse effect caused by using the tube pump, that is, the abrasion of the liquid delivery tube and the variation in the liquid delivery amount.

When the control unit commands the dispensing air cylinder to generate a positive pressure in the sample container, the positive pressure generated causes the eluate remaining in the eluate feed tube to be pushed out into the storage container. To return. Therefore, since the eluent does not remain in the eluate feed tube, the previous eluate does not mix into the sample container when the eluate is continuously dispensed into the sample container. The control unit further instructs the chemical liquid supply air cylinder to operate so as to generate a positive pressure in the fixed quantity container, and the positive pressure generated at that time causes the chemical liquid in the fixed quantity container to be transferred to the storage container through the chemical liquid supply tube. Press and transfer. Therefore, when replenishing the storage container with the chemical liquid as in the conventional case, the harmful effect caused by using the tube pump,
That is, it is possible to suppress the wear of the liquid feeding tube and the fluctuation of the liquid feeding amount.

[0011]

EXAMPLE As shown in FIG. 1, an elution test autosampler 6 according to an embodiment of the present invention comprises six flasks 7 as accommodating containers for accommodating solid preparations for internal use, and elution in the flask 7. Chemical solution supply unit 8 for supplying a supplementary test chemical solution
A closed sampling bottle 9 as a sample container, a turntable 10 for sequentially moving the sampling bottle 9 to a sampling position, a nozzle moving mechanism 11, and a piston type air cylinder 12 for dispensing. . In the sampling bottle 9, the eluate 70 eluted from the formulation by the drug solution in the flask 7 is sampled.

Each of the flasks 7 has about 1000 ml.
It is a glass container which has a capacity of 6 and comprises 6 sets. The flask 7 is housed in a thermostatic device having a heater unit (not shown), and the temperature of the chemical solution contained therein can be maintained at about 37 ° C. Inside the flask 7, a stirring blade (not shown) for stirring the chemical solution is arranged. Also, flask 7
One end of the liquid feeding tubes 15 and 16 is opened inside. The other end of the liquid supply tube 15 is connected to the chemical liquid supply unit 8.

The chemical liquid supply section 8 includes a replenishment container 17 for containing the chemical liquid for dissolution test, a fixed amount container 18, and an air pump 19.
And a piston type cylinder 20 for supplying a chemical solution. As shown in FIGS. 2 and 3, the replenishment container 17 is housed in a constant temperature bath 21 that holds the injected dissolution test chemical solution at about 37 ° C., and has a lid 17a capable of hermetically sealing the inside. ing. An end of the air supply tube 22 is opened in the replenishment container 17. The other end of the air supply tube 22 is connected to the discharge port of the air pump 19. A branch pipe 24 is connected to the air supply tube 22 via a three-way branch pipe 23, and the branch pipe 24 is provided with a first pinch valve 25 for opening and closing a vent.

Inside the replenishing container 17, one end of a liquid feeding tube 27 having a filter 26 at its tip is opened. The other end of the liquid feeding tube 27 is connected to the fixed quantity container 18. The liquid feeding tube 27 is provided with a second pinch valve 28. The fixed quantity container 18 is provided with a level sensor 29 for monitoring the amount of liquid fed from the replenishing container 17 so that the liquid surface is constant. The level sensor 29 may be a float type sensor or a capacitance type sensor.
A fourth pinch valve 30 for draining liquid is connected to the bottom of the fixed quantity container 18. Further, the fixed quantity container 18 is open at each end of the liquid feeding tube 15 and the other end of the air feeding tube 31 whose one end is connected to the cylinder 20.

A branch pipe 33 is connected to the air supply tube 31 via a three-way branch pipe 32, and the branch pipe 33 is provided with a third pinch valve 34 for removing the residual pressure of the metering container 18. . The first to fourth pinch valves described above have a structure in which the respective tubes are pressed to open and close the piping paths so that they do not come into direct contact with the chemical liquid, and therefore there are very few failures. The cylinder 20 has a motor 35.
And a ball screw 36 connected to the rotary shaft of the motor 35.
A moving body 37 engaged with the ball screw 36, and a cylinder body 38 having a piston 38a connected to the moving body 37. A connection port 39 is formed at the end of the cylinder body 38, and the other end of the air supply tube 31 is connected thereto.

On the other hand, the other end of the liquid feed tube 16 having one end connected to the flask 7 is connected to one of the nozzles 40 which will be described later and which constitutes a part of the nozzle moving mechanism 11. A spectrometer 42 composed of six flow cells 41 is installed in a part of the liquid feeding tube 16, and the translucency of the drug solution (eluent) fed into each tube 16 can be measured. The turntable 10 is arranged below the nozzle 40.

As shown in FIGS. 4 to 6, the turntable 10 is mainly composed of a table body 43 and a motor 44 for rotating the table body 43. A sample bottle storage hole 45 is formed on the upper surface of the table body 43. Six sample bottle storage holes 45 are formed in a row in the radial direction, and 16 rows are radially formed. This enables sampling in a total of 96 storage holes 45 in 16 steps. In addition, six of the sample bottles containing the cleaning liquid are stored in one row. At the center of the lower surface of the table body 43, a pulley 47 is installed via a shaft 46. A pulley 48 is installed on the rotation shaft of the motor 44 (FIG. 5). A belt 49 is wound around the two pulleys 47, 48 so that the rotational force of the motor 44 can be transmitted to the table body 43. The nozzle moving mechanism 11 is provided above the table body 43.
Is arranged.

The nozzle moving mechanism 11 is inserted into a septum formed in the center of the lid of the sample bottle 9 and
6 sets of nozzles 40 capable of holding the nozzles in a sealed state, a nozzle mover 50 fixing each nozzle 40, and a mover lifting device 5
1 and 1. The nozzle 40 includes a nozzle 40a as a first nozzle and a nozzle 40 as a second nozzle.
Two b's form one set, and six sets (a total of twelve) are fixed in parallel with each other with their tips facing downward. A lateral hole (not shown) is formed in the lower portion of each nozzle 40 in a direction substantially orthogonal to the axis of the nozzle 40, and the lateral hole further opens above the nozzle 40. The nozzle 40a is connected to one end of the liquid supply tube 16 and the nozzle 40b is connected to one end of the air supply tube 59 in the upper opening of the nozzle 40 of each set.

The mover lifting device 51 is composed of a motor 52 and a ball screw 53 screwed to the rotary shaft of the motor 52 (FIG. 1). The nozzle mover 50 is connected to the lower end of the ball screw 53. With such a configuration, the rotational force of the motor 52 is transmitted to the nozzle mover 50 via the ball screw 53, and the six sets of nozzles 40 can be moved up and down.

On the other hand, the other end of each air supply tube 59 is connected to a part of the air cylinder 12. Air cylinder 12
Is the same as the cylinder 20.
Ball screw 55 connected to the rotary shaft of
5, a cylinder body 57 having a piston 57a connected to the mover 56, and an air chamber 58 communicating with the cylinder body 57. The other end of the air supply tube 59 is connected to the air chamber 58. With such a configuration, the rotational force of the motor 54 is transmitted through the ball screw 55 to the cylinder body 5
It is possible to raise and lower the piston 57a of No. 7 and perform a predetermined amount of intake and exhaust from the tip of the nozzle 40. As each of the tubes, a Teflon tube having an inner diameter of 1 mm and an outer diameter of 2 mm is used, and one set of six tubes is adjusted to have substantially the same length.
As a result, the deformation of each tube during intake and exhaust can be kept constant, and variations in the amount of liquid / air supplied can be suppressed.

As shown in the block diagram of FIG. 7, the dissolution test autosampler 6 includes a CPU, a ROM, and an RA.
It has a control unit 60 including a microcomputer having an M, a timer, a counter, and the like. The control unit 60 includes
The key input unit 61 and the level sensor 29 are connected.
In addition, the control unit 60 includes a motor 35, 44, 52, 54, an air pump 19, and a first drive unit via a drive circuit unit (not shown).
~ 4 pinch valves 25, 28, 34, 30, spectrometer 42
And another input / output unit 62 is arranged.

The autosampler 6 of this embodiment performs the operations shown in the flow charts of FIGS. 8 to 12 according to the command of the command unit of the control unit 60. 13 to 15 show the piston 57 of the cylinder body 57 in each step described later.
a, the position of the nozzle mover 50, and the liquid level in the sample bottle 9 are shown. The procedure for using the autosampler 6 will be described below.

First, the preparation is set in the flask 7, the chemical solution for dissolution test is set in the fixed quantity container 18, and the closed sample bottle 9 is set in the turntable 10. When a predetermined input is made by the key input unit 61 and the auto sampler 6 is driven, initialization is performed at step S1. In this initial setting, each cylinder, pinch valve, etc. are set to the initial state. The positions of the piston 57a of the cylinder body 57 and the nozzle mover 50 at this time are shown in FIG. That is, the mover 50 is in the A position and the piston tip is in the S2 position.

When the initial setting is completed, the process proceeds to step S2 and the measurement mode is selected. When the measurement mode selected in step S2 is the sampling mode, the process proceeds to step S3 and the sampling mode is executed. When the predetermined sampling is executed in step S3, the process proceeds to step S4. In step S4,
The measurer determines whether or not the chemical solution is replenished. When the determination in step S4 is YES, the process proceeds to step S5 and the chemical replenishment mode is executed. NO in step S4
In this case, the measurer determines whether to proceed to step S6 and continue sampling. The determination in step S6 is Y
In the case of ES, the process proceeds to step S2. If the determination in step S6 is no, the process moves to step S7.

On the other hand, when the measurement mode selected in step S2 is the spectroscopic measurement mode, step S2
To S8, the spectroscopic measurement mode is executed.
When the predetermined spectroscopic measurement is executed in step S8,
The process moves from step S8 to step S6. Step S
At 7, the measurer determines whether or not to wash. When the determination in step S7 is YES, the process proceeds to step S9, and a predetermined cleaning mode is executed. If the determination in step S7 is no, this dissolution test ends.

The sampling mode will be described with reference to the flow chart shown in FIG. In the sampling mode, after a predetermined key input is made, step P1
At, it is determined whether the startup time has been reached. At the start-up time, for example, before the start of sampling, step P
Move to 2. In step P2, the turntable 10 is rotated and the sample bottle 9 is placed at the sampling position. Then, the process proceeds to step P3. In step P3, the nozzle mover 50 is moved to the B position (see FIG. 14). As a result, each nozzle 40 penetrates the septum of each sample bottle 9 and stops.

Then, the process proceeds to step P4. In Step P4, the air cylinder 12 is operated to move the piston 57a from the S2 position to the S3 position. As a result, the eluate 70 in the flask 7 is sucked up to the tip of the nozzle mover 50 through the liquid supply tube 16. Here, if spectroscopic measurement of the eluate 70 is performed by the spectrometer 42, the operation of the air cylinder 12 is set to 2 to 5 in the next step P5.
Stop for 3 seconds. During this period, the spectrometer 42 can be driven to measure the elution degree of the preparation based on the translucency of the eluate 70.

Then, the process proceeds to step P6. In Step P6, the air cylinder 12 is operated to move the piston 57a from the S3 position to the S1 position. Then, the process proceeds to step P7. In step P7, the operation of the air cylinder 12 is stopped. As a result, the eluate 70 in the flask 7 is suctioned and separated into the sample bottle 9 through the nozzle 40. When a predetermined amount of the eluate 70 is dispensed into the sample bottle 9, the process proceeds to step P8. In Step P8, the air cylinder 12 is moved from the S1 position to the S2 position. As a result, the eluate 70 remaining in the liquid supply tube 16 is pushed back into the flask 7 by the positive pressure generated in the sample bottle 9. When the eluent 70 is removed from the liquid sending tube 16, the process proceeds to step P9. In Step P9,
The operation of the air cylinder 12 is stopped. Next, step P
Go to 10. In Step P10, the nozzle mover 5
0 is raised from the B position to the A position.

The chemical solution replenishing mode will be described with reference to the flow chart shown in FIG. First, step P1
At 1, the first pinch valve 25 is closed and the second and third pinch valves 28, 34 are opened. Next, step P1
The operation moves to 2 and the air pump 19 is driven. As a result, the positive pressure generated in the refill container 17 pushes down the liquid surface of the refill container 17, so that the liquid solution passes through the liquid feeding tube 27 and the fixed amount container 1
8 is injected. Next, in Step P13, it is determined whether or not the level sensor 29 of the fixed quantity container 18 has detected the liquid surface. When the level sensor 29 detects the liquid surface, the process proceeds to step P14 and the driving of the air pump 19 is stopped. Thereby, the fixed quantity container 18 is filled with the fixed amount of the chemical liquid.

Then, the process proceeds to step P15, the first pinch valve 25 is opened, and the second pinch valve 28 and the third pinch valve 34 are closed. When the above valve operation is performed, the process proceeds to step P16. In Step P16,
The air cylinder 20 is moved from the S1 position to the S2 position as in FIG.
It is moved to the position (the air cylinder 20 has the same structure as the air cylinder 12 and is not separately shown). As a result, the drug solution in the fixed quantity container 18 is pressed and transferred to the flask 7 via the liquid supply tube 15. As a result, the same amount of the chemical liquid dispensed into the sample bottle 9 in step P6 is replenished in the flask 7, and the liquid level in the flask 7 is kept constant. Then, the process proceeds to step P17. Step P
At 17, the air cylinder 20 is raised from the S2 position to the S1 position. As a result, the liquid medicine remaining in the liquid supply tube 15 is returned to the fixed quantity container 18. Therefore, since the chemical liquid remaining in the liquid supply tube 15 is not added to the new chemical liquid dispensed from the fixed quantity container 18 to increase the amount of the liquid in the flask 7, the measurement accuracy is maintained. When the liquid medicine remaining in the liquid supply tube 15 is returned to the fixed quantity container 18,
Then, in Step P18, the third pinch valve 34 is opened. As a result, the pressure inside the fixed quantity container 18 is released.

The spectroscopic measurement mode will be described with reference to FIG. After key input in step P19, the process proceeds to step P20. In Step P20, it is determined whether or not the activation time has been reached. When the activation time, for example, before the start of sampling, the process proceeds to step P21. In Step P21, the turntable 10 is rotated and the sample bottle 9 is placed at the sampling position. Next, step P2
Move to 2. In Step P22, the nozzle mover 50 is moved to the B position. As a result, each nozzle 40 penetrates the septum of each sample bottle 9 and stops.

Then, the process proceeds to step P23. At step P23, the air cylinder 12 is operated to operate the piston 57.
Move a to the S2 position. This allows flask 7
The eluate 70 therein is sent to the tip of the nozzle mover 50 through the solution sending tube 16. Next, in Step P24, the operation of the air cylinder 12 is stopped for 2 to 3 seconds. Next, in Step P25, the eluate 70 is measured by the spectrometer 42.
Spectroscopic measurement. Thereby, the elution degree of the preparation is measured based on the translucency of the eluate 70.

Then, the process proceeds to step P26. In Step P26, the air cylinder 12 is moved from the S1 position to the S2 position. As a result, the eluent 70 remaining in the liquid feeding tube 16 is returned to the flask 7 by the positive pressure generated in the sample bottle 9. The eluent 70 is the liquid delivery tube 16
When it is removed from the inside, the process proceeds to step P27. In Step P27, the nozzle mover 50 is moved from the B position to the A position. Next, in step P28, the operator determines whether or not to continue sampling. If the determination in step P28 is no, the sampling ends. If the determination in step P28 is YES, the process proceeds to step P20 to continue sampling.

Finally, the cleaning mode will be described with reference to FIG. After the key input, in step P29, the turntable 10 is rotated to place the sample bottle 9 in the 16th step at the sampling position. Then, the process proceeds to step P30. At step P30, set the air cylinder 12 to S2.
Raise from position to S1 position. Next, step P3
Move to 1. In Step P31, the nozzle mover 50 is moved from the A position to the C position (see FIG. 15). As a result, each nozzle 40 penetrates the septum of each sample bottle 9 and stops. Then, the process proceeds to step P32. In step P32, the air cylinder 12 is operated to activate the piston 5
7a is lowered to the S2 position. As a result, the cleaning liquid in the sample bottle 9 passes through the liquid feeding tube 16 and the flask 7
Sent to

Next, in Step P34, the nozzle mover 50 is raised from the C position to the B position. Then, the process proceeds to step P35. In Step P35, the air cylinder 12 is moved from the S2 position to the S4 position. As a result, the cleaning liquid remaining in the liquid supply tube 16 is returned to the flask 7 by the positive pressure generated in the sample bottle 9. Then, the process proceeds to step P36. In Step P36, the nozzle mover 50 is moved from the B position to the A position. This completes a series of measurements.

In the above-mentioned embodiment, the eluate 70 of the flask 7 is sampled in the sample bottle 13 by using the negative pressure of the syringe 12 using the liquid feeding tube 16 made of Teflon. The tube wear is significantly reduced compared to an auto sampler consisting of a silicone feed tube. In addition, since the chemical solution is supplied from the chemical solution supply unit 8 to the flask 7 by using the positive pressure of the cylinder 20 by using the Teflon solution supply tube 15, the chemical solution and the eluate 70 to be replenished in the flask 7 are Because of the separate path, both liquids remaining in the tube are not contaminated as in the conventional case.
Further, since the cleaning mode is performed by using the above-mentioned members for sampling, it is not necessary to separately provide a dedicated cleaning mechanism, and the configuration of the entire apparatus can be simplified.

Further, the air cylinder 12 is actuated to suck and dispense the eluate 70 from the flask 7 into the sample bottle 9 by the negative pressure generated in each sample bottle 13, and then the air cylinder 1
By operating 2 in the opposite direction, the eluent 70 remaining in the liquid feeding tube 16 can be returned to the flask 7 by the positive pressure generated in each sample bottle 9, so that the eluent 70 remaining in the liquid feeding tube 16 is removed. It does not mix with the eluate 70 that is newly sent. For this reason, the liquid transfer amount is maintained constant and the measurement accuracy is improved. Although the sample bottle 9 is moved to the sampling position by using the turntable 10 in the above-described embodiment, the sample bottle 9 is moved by using the test tube rack.
May be horizontally moved.

In the above embodiment, the teaching method is used to set the sampling amount of the eluate 70 and the replenisher injection amount.
An air cylinder control using a plurality of positioning sensors or a time control method using a simple timer may be used. In the above embodiment, the length of the pipe is the same for all 6 stations,
Although the sampling amount from the flask 7 is adjusted by one cylinder body 57 as the inner diameter, the sampling amount may be individually adjusted by two or more or six cylinder bodies.

In addition, in the above-mentioned embodiment, based on the "dissolution test method", a set of six flasks, a flask 7, a turntable 1
Although 0, the liquid feeding tubes 15 and 16 and the air feeding tube 52 are set respectively, the number of the members may be one or 6
The number is not limited to one and may be plural.

[0040]

According to the automatic sampler for dissolution test according to claim 1 of the present invention, the air cylinder for dispensing is operated to generate a negative pressure in the sample container so that the eluate in the storage container is transferred to the sample container. Dispense by suction. Therefore, when dispensing the eluate into the sample container as in the past, the adverse effect caused by using the tube pump, that is, the measurement error due to the squeezing of a small amount of powder contained in the eluate eluted from the formulation is eliminated. To be done. Further, the adherence of the eluted substance in the path is eliminated, and the measurement error caused by the variation of the sampling liquid amount is eliminated. Furthermore, since there is no wear of the liquid delivery tube due to contact with the tube pump, maintenance of the device becomes easy.

According to the autosampler for dissolution test of the second aspect, after the eluate is dispensed from the storage container to the sample container, the dispensing air cylinder is operated to generate a positive pressure in the sample container. The eluate remaining in the eluate delivery tube is pushed back to the storage container. Therefore, since the eluent does not remain in the eluate feed tube, the previous eluate does not mix into the sample container when the eluate is continuously dispensed into the sample container. Therefore, the measurement error caused by the variation of the sampling liquid amount is eliminated.

According to the auto sampler for dissolution test of the third aspect, the chemical liquid supply air cylinder is operated to generate a positive pressure in the fixed quantity container to press and transfer the liquid medicine in the fixed quantity container to the storage container. For this reason, when replenishing the storage container with the chemical liquid as in the conventional case, there is no adverse effect caused by using the tube pump, that is, there is no wear of the liquid delivery tube due to contact with the tube pump, and therefore maintenance of the device is facilitated. . These above-mentioned inventions reduce adverse effects associated with the use of mechanical parts such as a tube pump and a solenoid valve in the liquid-sending path, fluctuations in the liquid-sending amount due to wear of the silicon tube, and the complexity of the work of replacing the solenoid valve or multiple tubes. Is solved.

Further, after the control unit sucks and dispenses the eluate into the sample container by the negative pressure generated by the operation of the dispensing air cylinder, the dispensing air cylinder is caused to perform an operation opposite to this sampling operation. Only by the generated positive pressure, the eluate remaining in the eluate delivery tube can be pushed back to the storage container. Therefore, the measurement error caused by the variation of the sampling liquid amount can be eliminated and the measurement can be performed with high accuracy by a simple device configuration.

On the other hand, since the replenishing chemical solution and the sampled eluate pass through different paths, each solution is contaminated by mixing each residual solution into the other by passing both solutions through the same path as in the conventional case. Never. Further, there is no need to use an expensive ceramic solenoid valve for switching the flow path. With such a configuration, it is possible to provide an elution test autosampler that suppresses wear of the liquid feed tube and fluctuations in the liquid feed amount, is easy to maintain and manage, and can maintain high measurement accuracy.

[Brief description of drawings]

FIG. 1 is a piping diagram of an autosampler for dissolution test according to an embodiment of the present invention.

FIG. 2 is a front view of a replenishing container forming the auto sampler of FIG.

FIG. 3 is a plan view of the refill container of FIG.

FIG. 4 is a plan view of the auto sampler shown in FIG.

5 is a side view of the auto sampler of FIG.

6 is a front view of the auto sampler of FIG.

FIG. 7 is a block diagram of a control unit of the auto sampler.

FIG. 8 is a flowchart of a control unit of the auto sampler.

FIG. 9 is a flowchart of a sampling mode.

FIG. 10 is a flowchart of a chemical solution replenishment mode.

FIG. 11 is a flowchart of a spectroscopic measurement mode.

FIG. 12 is a flowchart of a cleaning mode.

FIG. 13 is a schematic diagram showing a state of each unit before sampling.

FIG. 14 is a schematic diagram showing a state of each part after sampling.

FIG. 15 is a schematic view showing a state of each part in a cleaning process.

FIG. 16 is a schematic view showing a conventional example of an auto sampler.

[Explanation of symbols]

6 Autosampler 7 Flask (storage container) 8 Chemical supply part 9 Sample bottle (sample container) 11 Nozzle moving mechanism part 12 Air cylinder (for dispensing) 15 Liquid feeding tube (chemical liquid feeding tube) 16 Liquid feeding tube (eluent) Liquid feeding tube) 17 Replenishing container 18 Fixed amount container 20 Air cylinder (for supplying chemical liquid) 40 Nozzle (40a 1st nozzle / 40b)
Second nozzle) 59 Air supply tube (gas suction tube) 70 Eluent

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI technical display location G01N 1/28 35/10

Claims (3)

[Claims] 1. A storage container for storing an internal solid preparation as a dissolution test sample, a chemical solution supply section for supplying a dissolution test chemical solution to the storage container for storing the preparation, and a chemical solution supplied from the chemical solution supply section. A closable sample container into which the eluate eluted from the formulation is dispensed, an eluate delivery tube having one end opening into the storage container and a first nozzle at the other end, and a dispensing air cylinder, A gas suction tube having one end connected to a dispensing air cylinder and a second nozzle at the other end; and a nozzle moving mechanism that holds the first and second nozzles and inserts and detaches the tip of each nozzle into and out of the sample container,
A negative pressure generated when the control unit commands the operation of the dispensing air cylinder to generate a negative pressure in the sample container. An autosampler for dissolution test that dispenses the eluate from the storage container to the sample container by suction. 2. When the control unit instructs the dispensing air cylinder to operate so as to generate a positive pressure in the sample container,
The autosampler for elution test according to claim 1, wherein the eluate remaining in the eluate delivery tube is extruded and returned to the storage container by the generated positive pressure. 3. A drug solution supply unit, a fixed quantity container for containing a fixed amount of a dissolution test drug solution to be replenished in a storage container, and a drug solution feeding tube having one end opened to the fixed quantity container and the other end opened to the storage container. The metering container is provided with a chemical liquid supply air cylinder having an air discharge port, and the control unit instructs the chemical liquid supply air cylinder to operate so as to further generate a positive pressure in the metering container. The autosampler for dissolution test according to claim 1, wherein the chemical liquid in the fixed quantity container is pressed and transferred to the storage container by pressure through the chemical liquid supply tube.